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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 40 (1997), S. 939-945 
    ISSN: 1530-0358
    Keywords: Laparoscopy ; Port site implants ; Colectomy ; Complications ; Pneumoperitoneum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract BACKGROUND: An increased risk of laparoscopic port wound tumor implantation in the presence of overt or covert abdominal malignancy has been identified. PURPOSE: A porcine laparoscopic colectomy model has been used to quantify the influence surgical practices may have on tumor cell implantation. METHODS:51Cr-labeled, fixed HeLa cells were injected intraperitoneally before surgery. Tumor cell contamination of instruments, ports, security threads, and excised wound margins was assessed by gamma counting. RESULTS: Greatest contamination occurred in ports used by the operating surgeon under pneumoperitoneum (64 percent of all port wound tumor cells) and mechanical elevation (76 percent). Gasless surgery in patients in the head-down position increased the rostral accumulation of tumor cells in the abdomen and right upper quadrant port wound by 330 and 176 percent, respectively. Under pneumoperitoneum, port movement was the major contributor to port leakage and wound contamination (21 percent of total recovered wound tumor cells per port). Tumor cells were not carried in aerosol form. Instrument passage and the withdrawal of security threads through the abdominal wall increased port wound contamination 430 and 263 percent, respectively, over pneumoperitoneum control ports. Preoperative lavage reduced by 61 percent, but did not eliminate, wound contamination. CONCLUSION: This porcine model may be used to evaluate surgical factors for the impact on port wound contamination.
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  • 2
    ISSN: 1530-0358
    Keywords: Abscess ; Computed tomography-guided drainage ; Complications ; Anastomotic leak
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: This study was designed to assess the efficacy of computed tomography-guided percutaneous abscess drainage in intestinal disease. METHODS: Retrospective chart review of patients who underwent percutaneous abscess drainage for complications of intestinal disease with or without surgery between 1990 and 1994. RESULTS: Eighty-two patients with 111 abscesses were identified. Causes of abscess included anastomotic leaks (35 percent), postoperative complications without leak (30 percent), and diverticular disease (23 percent). Complete success (no surgery necessary) was achieved in 53 of 82 patients (65 percent). Nine patients (11 percent) who underwent interval surgery were classified as having partial successes. Twenty-six of 26 (100 percent) well-defined unilocular collections containing pus were successfully drained. Complex abscesses (loculated, poorly defined, multiple, associated with fistula, draining feces) were successfully drained in 35 of 55 patients (63 percent). Success rates varied inversely with the number of complicating factors present. Apache II scores of 15 or higher were associated with decreased success rates. CONCLUSION: Percutaneous abscess drainage is a highly successful technique for treatment of patients with intra-abdominal infection related to intestinal disease. Although several factors are associated with decreased success rates and multiple complicating factors combine to reduce success rates, no identifiable factor or combination of factors preclude the possibility of a successful outcome.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 40 (1997), S. 257-262 
    ISSN: 1530-0358
    Keywords: Heal pouch-anal anastomosis ; Ulcerative colitis ; Crohn's disease ; Familial adenomatous polyposis ; Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: This study was designed to identify factors associated with pelvic pouch failure. METHOD: A retrospective review of patients undergoing the pelvic pouch procedure with a minimum of 30 months follow-up was conducted. RESULTS: A total of 551 patients had pelvic pouch procedures from 1981 to 1992. Forty-nine patients (8.8 percent) have undergone pouch excision, and 9 (1.6 percent) have been defunctioned, for 58 (10.5 percent) patients with pouch failure. Cause of failure was leakage from the ileoanal anastomosis (IAA) in 21 (39 percent) patients, poor functional results in 13 (23 percent), pouchitis in 7 (12 percent), pouch leakage in 7 (12 percent), perianal disease in 7 (12 percent), and miscellaneous in 3 (5.2 percent). Nine of 22 patients (41 percent) had pouch failure during the first two years, with 2 of 147 patients (1 percent) having failure during the last two years of the study. The 58 patients whose pouches failed (Group 1) were compared with the 493 patients whose pouches did not fail (Group 2). Handsewn IAA (P 〈0.001), tension on the IAA (P 〈0.001), use of a defunctioning ileostomy (P 〈0.01), a diagnosis of Crohn's disease (P 〈0.001), and a leak from the pouch (P 〈0.001) or the IAA (P 〈0.001) were associated with pouch failure. Pouchitis was not a risk factor. CONCLUSION: The majority of pouch failures were caused by leaks at the IAA. Although the leak rate remained stable, leaks following a stapled anastomosis seemed to have a better prognosis than leaks following a handsewn anastomosis. Experience with the pouch procedure and the management of complications likely plays an important role in decreasing the risk of pouch failure.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 40 (1997), S. 112-115 
    ISSN: 1530-0358
    Keywords: Stoma ; Laparoscopy ; Closed technique ; Complications ; Surgical technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Stoma creation often involves a separate laparotomy incision. Recently, laparoscopy was suggested to minimize the morbidity associated with conventional open stomal techniques. We describe and evaluate a technique of stoma creation done directly through the stoma site, avoiding both laparotomy and laparoscopy. METHODS: Charts of 36 patients who underwent attempted stoma creation using this closed technique were retrospectively reviewed. RESULTS: A total of 32 patients had stomas successfully created in this fashion (closed group); although four patients failed and required laparotomy (open group), there was an overall success rate of 89 percent. Blood loss (17±5 vs. 350±130 ml; P 〈.001), operative time (52±8 vs. 169±35 minutes; P 〈0.001), and complications (3/32 vs. 4/4;P 〈0.001) favored the closed group. No factors, including diagnosis, obesity, or previous abdominal surgery were identified that contraindicated use of the closed technique. CONCLUSIONS: Stomas can be safely made in a high proportion of patients without the need for laparotomy or laparoscopy. Failure of the closed technique identifies a group of patients who have a high associated operative time, blood loss, and morbidity when laparotomy is used for stoma creation and in whom laparoscopic procedures may improve results.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1530-0358
    Keywords: Rat ; Intraperitoneal ; 5-Fluorouracil ; Chlorhexidine ; Perforated colorectal cancer ; Recurrence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Colorectal cancer is a prevalent and mortal disease, resulting in nearly 55,000 deaths in the United States annually. Preoperative or intraoperative spillage of tumor cells because of perforation occurs in up to 10 percent of cases. When this spillage occurs, the chance of recurrence and death is dramatically increased. METHODS: In an effort to reduce the chance of recurrence and death, we used a rat model to evaluate the efficacies of intraperitoneal 5-fluorouracil and chlorhexidine in reducing the incidence of recurrence. Rats were injected with 10 mg/kg azoxymethane subcutaneously weekly for 12 weeks to induce colorectal cancers. At 20 weeks, subtotal colectomies were performed on rats with colorectal tumors and without peritoneal implants or liver metastases. At the time of surgery, a cut portion of the tumor was placed in the abdomen for 30 minutes; the rats then randomly received peritoneal irrigation with 5-fluorouracil, chlorhexidine, or sterile water (control). Eight weeks postoperatively a necropsy was performed. At that time, obvious and suspected recurrences and the anastomotic area were sampled for histologic evaluation. RESULTS: Significant differences were seen with chlorhexidine vs.water for gross tumor (P=0.05) and microscopic tumor (P 〈0.05). 5-Fluorouracil showed a greater rate of abscess formation vs.both control and chlorhexidine (P 〉0.05). CONCLUSIONS: Use of chlorhexidine intraperitoneal therapy at the time of the operation for perforated colorectal cancer significantly decreases the frequency of gross tumor recurrence but not total recurrences. Intraperitoneal 5-fluorouracil does not significantly decrease recurrence and may increase the risk of abscess when used intraoperatively.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1534-4681
    Keywords: Epithelial ovarian cancer ; Second-look laparotomy ; Complications ; Secondary cytoreduction ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The routine inclusion of second-look laparotomy in the management of patients with epithelial ovarian cancer is controversial. At issue is the justification of morbidity incumbent upon surgery and the possible survival benefit of secondary cytoreduction. Methods: The rate of major complications of surgery was assessed among 100 consecutive patients with FIGO stage III or IV epithelial ovarian cancer who underwent second-look laparotomy. All patients demonstrated a complete clinical and biochemical (CA125 〈35 U/ml) response to first-line therapy. Patients were stratified based on findings at surgery. Patients in group 1 (n=37) had a negative second-look laparotomy. Patients in group 2 (n=35) had only microscopically appreciable disease. Patients in group 3 (n=28) had macroscopic disease. Cytoreductive efforts aimed at resection of all macroscopic disease were carried out for patients in group 3. Results: Thirteen patients (13%) had 15 major complications at surgery. Comparison of the complication rates for patients in groups 1, 2, and 3, of 10%, 8.5%, and 21.4%, respectively, did not achieve statistical significance (p=0.228). The estimated 5-year survival for patients in groups 1, 2, and 3 of 63.9%, 39.8%, and 14.2%, did differ significantly (p〈0.0001). Cytoreductive efforts resulted in the resection of all macroscopic disease in 18 of 28 patients (64.2%) in group 3. The median survival for this group of 18 patients was 33 months, and estimated 5-year survival was 20%. These values do not differ significantly from those observed for patients in group 2. Conclusion: The major complication rate associated with second-look laparotomy is not prohibitive Secondary cytoreductive efforts may result in improved survival for patients with epithelial ovarian cancer.
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  • 7
    ISSN: 1438-8359
    Keywords: Double-lumen tube ; Complications ; Tube troubles ; Airway obstruction ; One-lung ventilation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose Several case reports indicate critical respiratory complications in relation to the double-lumen endobronchial tube (DLT). A prospective survey for the airway problems in using the DLT is presented. Methods One hundred adult patients undergoing thoracotomy for lung cancer were investigated. Tube malposition and airway obstruction were searched using a fiber-optic scope. The endobronchial cuff was positioned just below the trachcal carina while the trachea was intubated with a DLT (Rüsch). The distances of displacement, from the tracheal carina to the bronchial cuff, were measured during anesthesia using an epidural catheter, which had marks every 5 mm. The distances for correcting the tube position were measured at both the bronchial cuff and the level of the teethPaO2,PaCO2 andSPO2 were also measured. Results Malposition (displacement over 5 mm from the correct position) was found in 42 patients, and 40 of them were in a withdrawal direction, occurring at the postural change and during one-lung ventilation, especially during manipulation of the lung hilum. Correcting distances at the level of the teeth were 15.3–3-times longer than those at the bronchial cuff. Airway deformities and gradual withdrawal of the bronchial cuff were found in association with surgical manipulation. Obstruction occurred at the tips of the tracheal tube in four patients and the bronchial tube in six patients, and at the tip of both in two patients. Hypoxemia (PaO2〈60 mmHg) occurred in four patients and hypercapnea (PaCO2〉60 mm Hg) in two patients. Conclusion Most of the DLT obstructions were associated with withdrawal malposition. Great attention to DLT displacement and airway deformity is advised.
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  • 8
    ISSN: 1435-1803
    Keywords: Rat ; collagen ; developed pressure ; pressure-volume relationships ; extracellular matrix
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: The impact of acute collagen disruption by the disulfide donor, 5,5′-dithio-2-nitrobenzoic acid (DTNB) on ventricular properties was tested in rat hearts.Methods: Collagen was degraded acutely in 13 isolated, isovlumically contracting rat hearts by perfusion with 1 mM DTNB added to Krebs-Henseleit solution for 1 hour followed by 2-hour perfusion with normal solution. Another 13 hearts were perfused with normal solution for 3 hours (Control).Results: Collagen content was 3.5±0.5% of ventricular dry weight in control group compared with 2.1±0.4% in DTNB group (decrease by 40%, p〈0.01). Scanning electron micrographs revealed loss of the delicate collagen network surrounding muscle fibers in DTNB treated hearts. Developed pressure at a fixed volume decreased to 86±17% of the baseline value after 3-hour perfusion in the control group, whereas in DTNB treated hearts developed pressure fell to 68±13% (p〈0.01). End-diastolic pressure was set at 5 mmHg at the beginning of the experiment and rose to 15±8 mmHg in control and 30±13 mmHg (p〈0.01) in the treated hearts. Concomitantly, wet-to-dry weight ratio increased from 5.63±0.26 in control to 6.07±0.11 (p〈0.05) in the DTNB treated hearts. A separate set of experiments on isolated myocytes excluded the possibility of a direct effect of DTNB on myocyte contractile function.Conclusions: These data suggested that with 40% collagen disruption by DTNB there is a significant increase in tissue edema that results in a decrease in chamber capacitance; in addition, there is a significant decrease in systolic performance which reflects the combined effect of edema and loss of collagen.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Gefässchirurgie 2 (1997), S. 144-149 
    ISSN: 1434-3932
    Keywords: Schlüsselwörter Shunt ; Dialyse ; Offenheitsrate ; Komplikation ; Key words Fistula ; Hemodialysis ; Patency rate ; Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract This paper reports our experience in surgery for hemodialysis access. In the period from 1983 to 1995, 728 operative procedures for hemodialysis access shunts were carried out. These were performed in 391 patients. A total of 599 shunts were placed as the primary form of access, including 423 autologous fistulas in the forearm and 144 in the upper arm. Additionally, 30 PTFE grafts were placed. As proposed, we have seen good functional results of the Brescia-Cimino-fistula in the forearm. Shunts in the upper arm show similar results but a higher rate of complications. PTFE grafts are associated with multiple complications and show a significantly lower rate of patency.
    Notes: Zusammenfassung Ziel der Arbeit ist die Darstellung eigener Erfahrungen als gefäßchirurgisches Zentrum mit der Dialyseshuntchirurgie. Im Zeitraum von 1983–1995 erfolgten in unserer Klinik insgesamt 728 shuntchirurgische Eingriffe an 391 Patienten; 599 Eingriffe waren Neuanlagen von Dialyseshunts. Als autologe Dialysefisteln wurden 423 am Unterarm und 144 am Oberarm angelegt. Bei 30 Dialyseshunts erfolgte die Anlage unter Verwendung von Gefäßprothesen. Erwartungsgemäß fanden sich gute Ergebnisse für die Brescia-Cimino-Fistel am Unterarm. Oberarmfisteln wiesen bei höherer Komplikationsrate gleich gute funktionelle Ergebnisse auf. Prothesenshunts waren komplikationsträchtig und zeigten signifikant schlechtere Funktionszeiten.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Gefässchirurgie 2 (1997), S. 65-68 
    ISSN: 1434-3932
    Keywords: Schlüsselwörter Glutealnekrose ; Aortoiliakale Chirurgie ; Komplikationen ; Key words Gluteal necrosis ; Aorto-iliac surgery ; Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Chronic hypoperfusion of the hypogastric arteries due to aortoiliac surgery leads to a complex of symptoms well known as Lerich's syndome. In contrast, acute ischemia of the pelvic arterial tree leads to lethal complications [2, 4, 5, 9, 10, 12, 13]. Acute interruption of the hypogastric perfusion mainly occurs after aortoiliac surgery or after selective transcatheter embolisation of the internal iliac artery for control of pelvic bleeding [1, 8]. Several complications may occur after total occlusion: urinary bladder necrosis [6], left colon ischemia, spinal cord ischemia [10], nerve palsy, necrosis of the rectum and gluteal musculature [2, 11–13]. Despite adequate therapy, mortality is over 70% [2]. We report the case of a 66-year-old patient who survived after acute occlusion of the iliac arteries with gluteal necrosis following replacement of the infrarenal aorta with an aortobiiliacal graft.
    Notes: Zusammenfassung Die chronische Minderperfusion im aortoiliakalen Stromgebiet führt zu einem Symptomenkomplex, der als Leriche-Syndrom bekannt ist. Im Gegensatz dazu drohen bei akuter Ischämie nach Verschluß der Beckenarterien schwere Komplikationen mit teilweise letalem Ausgang [2, 4, 5, 9, 10, 12, 13]. Die akute Unterbrechung der aortoiliakalen Perfusion wird überwiegend nach Eingiffen an der Aorta und den Beckenarterien, oder auch nach selektiver kathetergesteuerter Embolisation der Iliakalarterien zur Beherrschung von Blutungen im Beckenbereich beobachtet [1, 8]. Die verschiedenen Komplikationen verteilen sich auf Blasennekrosen [6], linksseitige Kolonischämien und Spinalarterienischämien [10], Nervenausfälle sowie Nekrosen des Rektums und der Glutealmuskulatur [2, 11–13]. Trotz adäquater Therapie beträgt die Letalität über 70% [2]. Wir berichten über einen 66jährigen Patienten, bei dem nach Ausschaltung eines rechtsseitig gedeckt rupturierten Iliakalaneurysmas durch eine Y-Prothese aufgrund eines beidseitigen Verschlusses der Aa. iliacae internae eine bilaterale Glutealnekrose auftrat, der aber dennoch diese meist letale Komplikation überlebte.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Der Chirurg 68 (1997), S. 395-402 
    ISSN: 1433-0385
    Keywords: Key words: Laparoscopic cholecystectomy ; Complications ; Legal consequences. ; Schlüsselwörter: Laparoskopische Cholecystektomie ; Komplikationen ; forensische Konsequenzen.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Mit zunehmender Etablierung der laparoskopischen Cholecystektomie treten seit einigen Jahren juristische Aspekte in den Vordergrund. Zur Klärung der Frage, welche Folgen eine kompliziert oder auch fehlerhaft verlaufene laparoskopische Cholecystektomie in juristischer Hinsicht nach sich zieht, wurden die erreichbaren Entscheidungen der Schlichtungsstellen der Ärztekammern sowie der Gerichte aufgearbeitet. Von 40 ausgewerteten Fällen von Behandlungsfehlervorwürfen wurden 16 als Behandlungsfehler anerkannt, 24 mal wurden die Vorwürfe zurückgewiesen. Der häufigste Vorwurf betraf mit 26 Fällen die Gallenwegverletzung. Von diesen 26 Verletzungen wurden 7 als Behandlungsfehler anerkannt, davon 2 als schwere Behandlungsfehler. Als Gründe für anerkannte Behandlungsfehler wurden in den Urteilen im wesentlichen ein verzögertes Umsteigen auf die konventionelle Operation, eine verzögerte Revision, die laparoskopische Durchführung einer Revisionsoperation und das fehlende Umsteigen bei unübersichtlichem Situs genannt.
    Notes: Summary. As laparoscopic cholecystectomy becomes more established, interest in legal aspects increases. The legal cases dealt with in Germany since the introduction of this laparoscopic method in 1989 were studied to determine the legal consequences of complications. Of 40 cases, 16 were judged to be cases of malpractice, whereas 24 were not. The most common cause was injury of the common bile duct (26 cases). Seven of these 26 cases were judged to be cases of malpractice, 2 of these as grave errors. The main reasons for the acceptance of a case as malpractice were delay in changing to conventional cholecystectomy, delayed revision, laparoscopic revisions and not reverting to conventional cholecystectomy in unclear situations.
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  • 12
    ISSN: 1279-8509
    Keywords: Hemophilia ; Complications ; Africa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to describe the presenting features at diagnosis and complications of hemophilia in Dakar, we conducted a study of hospital records between October 1991 and January 1993. Twenty-five cases of hemophilia were identified. We found that only 4% of our patients were diagnosed in the first 6 months of life whereas 64% of patients were diagnosed between 6 months and 5 years of age, 32% were detected between 5 years and 14 years of age. The presenting feature at diagnosis was external bleeding in 60% of cases and internal bleeding in 40%. 92% of cases were hemophilia type A and only 8% hemophilia type B. 56% of patients had mild hemophilia, 40% moderate and only 4% severe disease. Hemophiliac arthropathy was present on radiography in 76%. Complications were dominated by repeated joint bleeding, which was present in 92% of patients, and repeated hematomas (80% of patients). A functional handicap was present in 60% of cases. 12% of transfused hemophiliacs developed an inhibitor and 4% of patients were HIV positive. Greater awareness of hemophilia amongst the medical community as well as continued efforts to improve care for hemophiliacs in Senegal are necessary.
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  • 13
    ISSN: 1438-1435
    Keywords: Pancreatitis ; Pleural effusions ; Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recognition of pleural effusions in acute pancreatitis is important since it carries prognostic implications. This study evaluates the incidence and characteristics of pleural effusions on computed tomography (CT) of patients with mainly an alcohol ingestion etiology of acute pancreatitis. A review of medical records and abdominal CT scans in 50 patients with clinical and laboratory evidence of acute pancreatitis was carried out. All patients were referred for abdominal CT scanning based on an initial clinical presentation consistent with acute pancreatitis and had confirmatory elevation of the corresponding serum enzyme levels. The presence, laterality, and size of any pleural effusions were recorded from the initial sections through the lung bases. Based on a review of medical records, 36 patients (72%) had an alcohol-related etiology of acute pancreatitis. Overall, 10 patients (20%) with acute pancreatitis had pleural effusions on abdominal CT imaging. Five of the effusions were bilateral, three were unilateral right sided, and two were unilateral left sided. Nine of the effusions were small (〈1 cm in maximal height) or medium (1–2 cm) in size. Small and medium-sized pleural effusions are not uncommon in acute pancreatitis. The higher incidence in this study compared to that in earlier reports likely represents the increased sensitivity of cross-sectional imaging for small amounts of pleural fluid. The absence of left-sided effusion predominance in our study group is contrary to much of the earlier literature and may reflect demographic factors, such as etiology and previous history of pancreatitis, although statistical variability must also be considered.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 166-172 
    ISSN: 1432-1912
    Keywords: Key words Catalepsy ; VM nucleus ; Kainic lesions ; Pontine reticular formation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bilateral kainic acid lesions of the ventro-medial (VM) thalamic nucleus of rats which greatly reduced the catalepsy produced by haloperidol (2 mg/kg i.p.) not only did not reduce, but even enhanced, the cataleptogenic effect of eserine (1 mg/kg i.p.) and arecoline (30 mg/kg i.p.). This finding is in accord with former conclusions that catalepsy produced by cholinergic drugs does not depend on striatal mechanisms. In rats with kainic acid lesions of the VM thalamic nucleus, and similarly in intact, non-lesioned rats, systemic administration of eserine and arecoline potentiated the catalepsy produced by microinjections of carbachol (2 μg) into the pontine reticular formation (PRF). Atropine microinjected bilaterally into the PRF attenuated the cataleptogenic effect of eserine and arecoline i.p. We suggest that the PRF is a site at which systemically given cholinergic drugs act to produce catalepsy.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 364-367 
    ISSN: 1432-1912
    Keywords: Key words Capsaicin ; CGRP (calcitonin ; gene-related peptide) ; Endothelium-dependent ; relaxation ; Thoracic aorta ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have shown that pretreatment with calcitonin gene-related peptide (CGRP), a principal transmitter in sensory nerves, can protect the endothelial cell. We therefore evaluated whether in vivo capsaicin treatment prevents endothelial damage elicited by lysophosphatidylcholine (LPC) in the rat aorta. Acute treatment or repeated pretreatment with capsaicin resulted in stimulation of neurotransmitter release from sensory nerves or depletion of their transmitter content respectively. Vasodilator responses to acetylcholine (ACh) were examined in the aorta of these animals. Acute application of capsaicin (50 mg/kg) increased the plasma concentration of CGRP-like immunoreactivity (CGRP-LI) concomitantly with a reversal of the inhibition by LPC of endothelium-dependent ACh-induced relaxation in the isolated rat aorta. After repeated pretreatment with capsaicin to deplete sensory nerve neurotransmitter content the effects of capsaicin were absent as shown by the plasma CGRP-LI concentration and the vasodilator response to ACh. The results demonstrate that systemic capsaicin treatment, which evokes the release of CGRP from sensory nerves, protects the endothelial cell. The present study also suggests that CGRP may be an endogenous vascular protective substance.
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  • 16
    ISSN: 1432-1912
    Keywords: Key words Neuropeptide Y (NPY) ; Ca2+ efflux ; Y1 receptor ; Na+/Ca2+ exchange ; Na+ influx ; Cardiomyocyte ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several physiological stimuli cause a rise in intracellular Ca2+ concentration ([Ca2+]i) in cardiomyocytes. This increased [Ca2+]i must be restored to physiological resting level to ensure response to further stimuli. In the present study, we examined the effect of neuropeptide Y (NPY), which is secreted from certain adrenergic or non-adrenergic neurons, on Ca2+ efflux from freshly isolated, quiescent adult rat cardiomyocytes. The isolated cardiomyocytes were preloaded with 45CaCl2 for 1 h. Then, the fractional release of 45Ca2+ from the cells was measured. NPY stimulated the efflux of 45Ca2+ from isolated adult rat cardiomyocytes in a concentration-dependent manner (10–8 M to 10–6 M). NPY (10–6 M)-induced Ca2+ efflux was 2.0 ± 0.16% of the total cellular content. The 45Ca2+ efflux from the cells was also stimulated by Y1 receptor agonist, [Leu31, Pro34]NPY, but not by Y2 receptor agonist, NPY13–36. The effect of NPY was inhibited by a peptide NPY inhibitor, NPY18–36 and a non-peptide NPY inhibitor, benextramine to a similar extent. From these results, it is conceivable that the effect of NPY on Ca2+ efflux from cardiomyocytes is mediated through Y1 receptors. It was also observed that NPY caused a rise in [Ca2+]i to almost 150 nM. NPY-stimulated 45Ca2+ efflux was not affected by removal of extracellular Ca2+, but was dependent on the presence of extracellular Na+. Moreover, NPY caused a 22Na+ influx into the cells of about 1.6-fold over the basal value which was inhibited by amiloride and 5-(N,N-dimethyl)-amiloride, known Na+/Ca2+ exchange inhibitors. In addition, isoproterenol also caused 45Ca2+ efflux from the cells and which was enhanced by the addition of NPY. These results suggest that NPY stimulates extracellular Na+-dependent 45Ca2+ efflux from freshly isolated adult rat cardiomyocytes, probably through its stimulatory effect on plasma membrane Y1 receptors with which NPY may couple during Na+/Ca2+ exchange.
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  • 17
    ISSN: 1432-1912
    Keywords: Key words 5-Hydroxytryptamine ; 5-HT1A receptors ; Microdialysis ; Flesinoxan ; WAY 100635 ; 8-OH-DPAT ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The modulation of extracellular 5-hydroxytryptamine (5-HT) in the central nucleus of the amygdala (CeA) by 5-HT1A receptors was studied by intracerebral microdialysis in awake and freely moving rats. Local administration of 1 μM tetrodotoxin (TTX), 60 mM K+ and perfusion with Ca2+-free Ringer containing EGTA confirmed that the major part of dialysate 5-HT levels from the CeA is of neuronal origin. Administration of 300 nM of RU 24969, a 5-HT1B receptor agonist, through the probe into the CeA decreased dialysate 5-HT levels to 67.2% of the baseline value. Systemic administration of the 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan dose-dependently decreased 5-HT levels in the CeA. The effect of 0.3 mg/kg of flesinoxan could be completely antagonized by systemic administration of 0.05 mg/kg WAY 100635, a 5-HT1A receptor antagonist. WAY 100635 alone had only minimal effects at this dose. These data show that a major part of the extracellular 5-HT in the CeA stems from 5-HT neurons and that the amount of 5-HT released into this brain region can be modulated by 5-HT1A receptors.
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  • 18
    ISSN: 1432-0843
    Keywords: Key words Anthracyclines ; Daunorubicin ; Daunorubicinol ; Pharmacokinetics ; Rat ; Aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Age-related differences in pharmacokinetics may be important in determining altered anthracycline cardiotoxicity in the senescent rat and also in older humans. This study examined the effect of aging on daunorubicin pharmacokinetics in the Fischer 344 rat. Daunorubicin 7.5 mg/kg was administered i.v. to 6-and 24-month-old male Fischer 344 rats and plasma and tissue sampling was performed over 168 h for assay of daunorubicin and daunorubicinol concentrations by high-performance liquid chromatography. Systemic clearance of daunorubicin was decreased in older compared to younger animals (56±4 versus 202±17 ml min-1 kg-1; P〈0.05). In addition, the area under the plasma daunorubicinol concentration/time curve was significantly increased in older rats. In the heart, the area under the concentration/time curve was significantly increased in senescence both in the case of daunorubicin (201±12 versus 86±4 μg h g-1; P〈0.05) and daunorubicinol (1347±118 versus 182±4 μg h g-1; P〈0.05). Furthermore, the peak mean concentrations of daunorubicin were increased in older compared to younger rats both in plasma (1078±82 versus 663±66 ng ml-1; P〈0.05) and in heart (27±1 versus 10±1 μg g-1; P〈0.05). This also was true for daunorubicinol in plasma (284±39 versus 168±27 ng ml-1; P〈0.05) and in myocardium (8.6±0.6 versus 2.4±0.2 μg g-1; P〈0.05). Following daunorubicin injection, the ratio of daunorubicinol to daunorubicin concentrations in tissues increased with time, particularly in plasma and heart in senescent rats. Thus, there are significant age-related changes in daunorubicin and daunorubicinol kinetics in the rat that could alter susceptibility to acute systemic toxicity and to chronic cardiotoxicity.
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  • 19
    ISSN: 1433-044X
    Keywords: Schlüsselwörter Acetabulum ; Fraktur ; Operative Behandlung ; Komplikationen ; Ergebnisse ; Key words Acetabulum ; Fractures ; Operative treatment ; Complications ; Results
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Between December 1986 and November 1995, 222 patients with 225 acetabular fractures were treated operatively by three surgeons in the Department of Traumatology and Emergency Surgery of the University Hospitals of the Catholic University of Leuven. Indications for surgery were unstable fracture, displaced fracture through the acetabular dome and fracture with intra-acetabular fracture fragments. There were 37.3% A-fractures, 49.7% B-fractures, and 13% C fractures according to the AO Classification. In 16.4% of fractures there were primary neurological deficits. Patients were treated operatively after an average of 5.0 days. The Kocher-Langenbeck approach was used in 56.9% of cases, the ilio-inguinal approach in 27.1% and the extended iliofemoral approach in 4%. In 7.1% of patients, a primary total hip endoprosthesis was implanted. There was no intra- oder perioperative mortality. The average hospital stay was 26.1 days. In 7.1% of patients, we noted secondary neurological problems. Deep infections were present in 1.3%. In 11.1% of patients a second operative procedure was necessary. We were able to review 175 patients after an average of 2 years. Signs of arthrosis and periarticular ossification were noted on the x-rays: walking distance, hip mobility and pain intensity were asked about and recorded after the clinical examination. In 76% of patients an excellent or good result on the Merle-d'Aubigne scale was obtained. T-fractures and posterior wall fractures were followed by the worst results. During this 9-year period, changes have been made to the preoperative radiological examination carried out, the choice of operative approach and our policy on prevention of thrombosis prophylaxis and postoperative ossification. After thorough preoperative diagnosis and with a meticulous operative technique, it is possible to stabilise the vast majority of acetabular fractures through the three classical approaches. Because the fractures are relatively rare, their diagnosis complex and their surgical treatment difficult, specific training is essential for every acetabular surgeon.
    Notes: In der Zeit zwischen Dezember 1986 und November 1995 wurden in der Klinik für Unfall- und Notfallchirurgie der Universitätskliniken der Katholischen Universität Leuven 222 Patienten mit 225 Acetabulumfrakturen von drei Chirurgen operativ versorgt. Operationsindikationen bestanden bei instabilen Frakturen, verschobenen Frakturen durch das Acetabulumdach und Frakturen mit intraartikulären Frakturfragmenten. Es lagen in 37,3% A-Frakturen, in 49,7% B-Frakturen und in 13% C-Frakturen der AO-Klassifikation vor. Bei 16,4% der Frakturen waren präoperativ neurologische Ausfälle vorhanden. Die Patienten wurden durchschnittlich nach 5,0 Tagen operativ versorgt. Der Kocher-Langenbeck-Zugang wurde in 56,9% verwendet, der ilioinguinale Zugang in 27,1% und der erweiterte iliofemorale Zugang in 4%. Bei 7,1% der Patienten wurde primär eine Totalendoprothese implantiert. Es gab keine intra- oder perioperative Mortalität. Der durchschnittliche Krankenhausaufenthalt betrug 26,1 Tage. Bei 7,1% der Patienten bestanden sekundäre neurologische Probleme, Infektprobleme kamen in 1,3% vor, Sekundäreingriffe waren in 11,1% notwendig. 175 Patienten wurden nach einem durchschnittlichen Zeitraum von 2 Jahren nachuntersucht. Arthrosezeichen und periartikuläre Ossifikationen wurden röntgenologisch, Gehstrecke, Hüftmobilität und Schmerzintensität klinisch ausgewertet; 76% dieser Patienten erhielten ein sehr gutes bis gutes Ergebnis nach der Merle-D'Aubigne-Skala. Die schlechtesten Ergebnisse erhielten die T-Frakturen und die Hinterwandfrakturen. Im Laufe des Neunjahreszeitraums der Studie haben sich präoperative Röntgendiagnostik, die Wahl des operativen Zugangs und die postoperative Versorgung in Bezug auf Thromboseprophylaxe und Prävention von periartikulären Ossifikationen eingehend geändert. Nach ausführlicher präoperativer Diagnostik und mit sorgfältiger Operationstechnik ist es möglich, die Mehrheit der Acetabulumfrakturen durch die drei klassischen Zugänge zu operieren. Weil diese Frakturen eher selten sind, die Diagnostik mühsam und die chirurgische Technik sich schwierig gestaltet, ist eine spezifische Schulung für jeden Acetabulumchirurgen unerläßlich.
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  • 20
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    Monatsschrift Kinderheilkunde 145 (1997), S. 1286-1288 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Septumsabszeß ; Diagnose ; Komplikationen ; Kasuistik ; Key words Septal abscess ; Diagnosis ; Complications ; Case report
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Nasal abscesses are uncommon and therefore have been given little attention in the medical literatur. So there are possible diagnostical problems, especially in children. Immediate therapy is indicated to avoid cosmetic deformity or intracranial infections. Treatment entailsm surgical drainage, reconstruction of the septum, and adequate antibiotic backup. Discussion: Nasal septal abscesses should be considered whenever obstructions in nasal breathing with concomitant raised body temperature and swelling occur after trauma.
    Notes: Zusammenfassung Ein Nasenseptumhämatom bzw. -abszeß ist ein seltenes Krankheitsbild und wird in der medizinischen Fachliteratur nur wenig berücksichtigt. Das führt dazu, daß bei der Diagnose Schwierigkeiten bestehen, was v.a. bei Kindern der Fall zu sein scheint. Eine unmittelbare Therapie zur Vermeidung von kosmetischen Problemen bzw. intrakraniallen Komplikationen ist erforderlich. Diese besteht in einer Drainierung, Rekonstruktion des Septums bzw. antibiotischen Abschirmung. Diskussion: Bei einer nach Trauma auftretenden Behinderung der Nasenatmung mit Fieber und Schwellung ist an einen Septumabszeß zu denken.
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  • 21
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    Der Chirurg 68 (1997), S. 613-617 
    ISSN: 1433-0385
    Keywords: Key words: Outpatient laparoscopic cholecystectomy ; Outpatient clinic ; Prospective study ; Complications ; Costs ; Cost effective. ; Schlüsselwörter: Ambulante laparoskopische Cholecystektomie ; niedergelassene Operationseinrichtung ; prospektive Studie ; Komplikationen ; Kosten.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. In einer prospektiven Beobachtungsstudie wurden 140 Patienten erfaßt, die rein ambulant laparoskopisch cholecystektomiert wurden. Das Patientengut entspricht im wesentlichen den Veröffentlichungen stationär operierter Patienten. Es gab keine relevanten intra- und postoperativen Komplikationen. Postoperativ brauchten die Patienten weniger Schmerzmittel, erholten sich schneller und waren schneller wieder arbeitsfähig als Patienten in vergleichbaren Veröffentlichungen stationär operierter Patienten. Die ambulante laparoskopische Cholecystektomie ist eine gute Alternative für Patienten mit geringem oder mittlerem Risiko. Selbst bei verbesserter Ertragssituation für die Operationseinrichtung eröffnet sie außerdem Einsparpotentiale im Gesundheitssystem.
    Notes: Summary. A total of 140 patients underwent outpatient laparoscopic cholecystectomy in an outpatient clinic. Evaluation and follow-up of the patients were done prospectively. Population and preoperative data were comparable to published studies of patients operated on in hospitals. There were no serious intra- or postoperative complications. Postoperatively, patients needed less pain medication, were less tired and returned to work earlier than patients after clinical laparoscopic cholecystectomies. Outpatient laparoscopic cholecystectomy offers a good alternative to patients with moderate operative risks (ASA 1–3). It could reduce costs in the German health system and would be therefore highly cost effective.
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  • 22
    ISSN: 1433-0423
    Keywords: Key words Cytomegalovirus retinitis ; Intraocular sustained release device ; Complications ; Ablatio retinae ; CMV resistance ; Schlüsselwörter CMV-Retinitis ; Ganciclovir-Medikamententräger ; Pars-plana-Implantation ; Komplikationen ; Begleittherapie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Zytomegalievirus-(CMV)-Retinitis als häufigste opportunistische Infektion bei Patienten mit Aids wurde erstmals 1992 mit einem intraokular implantierten Medikamententräger therapiert. Im Jahr 1995 wurden die ersten Medikamententräger in Deutschland implantiert und im Rahmen einer offenen Studie der postoperative Verlauf, die Komplikationen und die Wirkdauer überprüft. Patienten und Methode: 20 Patienten wurden in die Studie eingeschlossen und insgesamt 32 Augen mit einem Ganciclovir-Medikamententräger (Vitrasert™, Fa. Chiron-Adatomed, München) versehen. Alle Patienten bekamen zusätzlich eine orale Ganciclovir- oder adjuvante i. v.-Therapie. Der Medikamententräger besteht aus Ethylenvinylazetat und enthält 4,5 mg Ganciclovir mit einer Freisetzungsrate von 1 μg/h Ganciclovir in den Glaskörper über eine prognostizierte Wirkdauer von 6–8 Monaten. Ergebnisse: Die schwerwiegendste Komplikation war die Ablatio retinae bei 5 Patienten (5 Augen), diese Inzidenz entspricht der Ablationshäufigkeit unserer konservativ (d. h. i. v. oder oral) behandelten Patienten. Resistenz gegen Ganciclovir und andere Nukleosidanaloga war die Ursache für die Progredienz der Retinitis nach Implantation bei 2 Patienten mit nachfolgender Erblindung. In keinem Fall wurde eine CMV-Neuinfektion der nicht betroffenen Augen gesehen, es wurden keine extraokularen CMV-Manifestationen unter systemischer antiviraler Begleittherapie festgestellt. Innerhalb des Untersuchungszeitraums von 12 Monaten trat kein Rezidiv auf. Schlußfolgerung: Die Implantation eines Ganciclovir-Medikamententrägers erlaubt eine zielgerichtete antivirale Therapie der CMV-Retinitis mit dem deutlichen Vorteil der wesentlich selteneren Rezidivhäufigkeit. Extraokulare und Zweitaugen-CMV-Infektionen können durch tolerable systemische Therapieschemata verhindert werden.
    Notes: Summary We performed an open clinical trial to assess the safety and efficacy of a 1 μg/h ganciclovir implant for the treatment of newly and pretreated cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Patients and methods: Thirty-two eyes (20 patients) received the ganciclovir intraocular device and were prospectively followed up from 30 to 365 days. We used a modified technique for fixation of the device in half of the patients. The modification improved the fixation of the implant with a two-hole technique in the strut. Results: Thirty eyes showed stabilization of the retinitis over the time, but in two patients resistance against ganciclovir and other nucleosid analogue compounds developed. Postoperative complications included vitreous hemorrhage (n = 1), cataract (n = 1), and uveitis anterior (n = 1). Late retinal detachment was seen in five eyes (25 %) at 30 to 60 days after implantation. Followup until 1 year after implantation did not show progression of CMV retinitis in 18 of 20 patients. All received antiviral CMV therapy to protect noninfected eyes and intestinum against CMV infection. Conclusions: The ganciclovir intraocular device seemed to be effective in most cases of CMV retinitis and offers a promising alternative for cytomegalovirus retinitis. Patients pretreated longer than 6 months with i. v. ganciclovir have to be carefully selected for implantation, because resistance against ganciclovir could be three times more likely than in i. v.-therapy naive patients.
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  • 23
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    Der Ophthalmologe 94 (1997), S. 50-52 
    ISSN: 1433-0423
    Keywords: Key words rTPA ; Fibrin ; Eye ; Anterior segment ; Complications ; Schlüsselwörter rTPA ; Fibrin ; Auge ; Vorderabschnitt ; Komplikationen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Seit einigen Jahren wird Gewebeplasminogenaktivator (rTPA) intraokular zur Behandlung persistierender Fibrinmembranen eingesetzt, ohne daß bisher nennenswerte Komplikationen beschrieben wurden. Wir berichten über unsere eigenen Erfahrungen beim Einsatz von rTPA im vorderen Augenabschnitt bei 25 Patienten. Über eine Parazentese wurden komplikationslos jeweils 25 µg rTPA (Actilyse, Dr. Karl Thomae GmbH) in die Vorderkammer gespritzt. Ein Rückgang des Fibrins war – wenn auch bei einigen Augen nur allmählich – in 21 Fällen zu verzeichnen. Als postoperative Komplikationen traten 2mal eine (beherrschbare) Nachblutung und 2mal eine irreversible oberflächliche Hornhauttrübung auf. Die Behandlung einer Fibrinmembran des vorderen Augenabschnitts mit rTPA stellt in vielen Fällen eine sinnvolle Ergänzung der lokalen Steroidgabe dar. Beunruhigend ist für uns jedoch das Auftreten von irreversiblen Hornhautkomplikationen, deren Pathogenese wir uns derzeit noch nicht erklären können. Aufgrund des eindeutigen zeitlichen Zusammenhangs müssen wir jedoch von einer kausalen bzw. toxischen Wirkung des rTPA selbst oder einer der Lösungskomponenten ausgehen.
    Notes: Recombinant tissue plasminogen activator (rTPA) is commonly used in patients with myocardial infarction. Recently, it has also been applied intraocularly to dissolve post-operative fibrin with no serious complications being reported so far. In this study we describe our own experience with rTPA in 25 patients with persisting fibrinous membranes in the anterior segment. rTPA (Actilyse, Dr. Karl Thomae GmbH) was given in a single dose of 25 µg and injected into the anterior chamber via a paracentesis. We did not encounter any complications during the injection of rTPA. In 21 eyes fibrin could be reduced significantly, albeit sometimes only slowly. In 13 patients, the membrane had dissolved almost completely by the following day. In contrast, no success was observed after glaucoma surgery (2 eyes) and in chronic iritis (1 eye), or when fibrin mixed with blood was treated (1 eye). There were two (controllable) post-operative hemorrhages (rTPA after vitrectomy, and for fibrin/blood after cataract surgery). In addition, we noted 2 cases of irreversible superficial corneal clouding (rTPA after cataract surgery). We conclude that injection of rTPA can be a useful addition to steroid treatment in selective cases of persisting fibrin in the anterior segment. Long-standing membranes, however, are unlikely to be dissolved. Care should also be taken and rTPA be avoided when there is evidence of recent bleeding. Most worrying to us were the corneal complications that we cannot explain to date. With regard to the definite time correlation we feel that rTPA or one of the solution components might be the cause of this unusual feature.
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  • 24
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    Der Orthopäde 26 (1997), S. 67-74 
    ISSN: 1433-0431
    Keywords: Schlüsselwörter Kongenitale Hüftluxation ; Offene Reposition ; Zugangswege ; Operationstechnik ; Komplikationen ; Femurkopfnekrose ; Reluxation ; Key words Congenital dislocation of the hip ; CDH ; DDH ; Open reduction ; Surgical approach ; Surgical technique ; Complications ; avascular necrosis ; Recurrent dislocation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Closed reduction of a hip dislocation will prove even more difficult if the dislocation has existed over a longer period of time. The indication is based on several principles: An open reduction may be carried out only after an unsuccessful attempt to perform a closed reduction or at a fixed age limit (12 or 24 months) or based upon arthrographic findings. In our department, for babies up to the age of 12 months, we always try to perform a closed reduction. Between 12 to 24 months, arthrographic findings will determine the choice of method. After the age of two, as a rule, we use an open reduction. The preliminary treatment consists of longitudinal traction. Current methods of approach to the hip joint are the medial approach according to Ludloff or the frontal approach by means of an inguinal incision. With the medial approach, there is greater risk of damaging the circumflex artery; also, a higher rate of avascular necrosis of the femoral head has been observed. Therefore, we only practice the ventral approach. Mainly for cosmetic reasons, however, instead of using the Smith-Petersen procedure, we apply a pure inguinal incision proximal to the inguinal ligament. The approach is found by detaching the muscle tissue at the anterior and interior iliac spine. Medially and laterally of the pelvic ridge, though, the tissue may be left. The joint capsule may be opened in the shape of a T or a V. A t-shape incision offers a better survey, wherby the risk of damaging a vessel is somewhat higher. In addition to resection of the teres ligament, it is necessary to indent the transverse acetabular ligament. Often, aponeurotic recession of the psoas tendon must be performed as well and the labrum indented and pushed outwards before reduction. The risk of insufficient development of the acetabulum can be minimized only if the femoral head is optimally centered. If the femoral head is in a high position (i. e., if the upper ridge of the femoral metaphysis lies higher than the triradiate cartilage), a shortening osteotomy of the femur should always be performed. This is the only possibility of repositioning the femoral head without exercizing exaggerated pressure. On the other hand, we are rather reticent to perform a pelvic osteotomy at the time of repositioning. For children unter 2 years of age, we recommend to that the acetabulum be allowed to develop and that a pelvic osteotomy be performed at a lager period if necessary. Postoperative treatment is given for a period of 12 weeks in a hip-leg cast in the Fettweis position, followed by another 3 months in a splint. Possible complications are redislocations, avascular necrosis of the femoral head and persistent acetabular dysplasia. An optimal technique will considerably reduce the risks of such complications.
    Notes: Zusammenfassung Je länger eine Hüftgelenkluxation besteht, desto schwieriger wird es, sie geschlossen zu reponieren. Für die Indikation der offenen Reposition kann nach verschiedenen Prinzipien vorgegangen werden. Sie kann entweder nur nach mißlungenem geschlossenem Repositionsversuch durchgeführt werden oder aufgrund einer starren Altersgrenze (12 oder 24 Monate) oder auf der Basis von arthrographischen Befunden. An unserer Klinik versuchen wir bis zum Alter von 12 Monaten stets primär geschlossen zu reponieren, zwischen 12 und 24 Monaten richten wir uns nach dem arthrographischen Befund, jenseits des 2. Lebensjahres reponieren wir stets von Anfang an offen. Als Vorbehandlung führen wir eine Extension durch. Als Zugänge zum Hüftgelenk sind der mediale Zugang nach Ludloff sowie der vordere Zugang durch Leistenschnitt gebräuchlich. Die Gefahr der Verletzung der A. circumflexa femoris ist beim medialen Zugang größer, es wurde auch eine höhere Rate von Femurkopfnekrosen beobachtet. Wir benutzen deshalb nur den ventralen Zugang. Die Gelenkkapsel kann T- oder V-förmig eröffnet werden. Die T-förmige Eröffnung erlaubt eine bessere Übersicht, die Gefahr der Gefäßverletzung ist aber etwas größer. Nur wenn es gelingt, den Femurkopf optimal zu zentrieren, kann das Risiko der ungenügenden Pfannenentwicklung minimiert werden. Bei hochstehendem Femurkopf (Oberrand der Femurmetaphyse höher als die Y-Fuge) sollte immer eine Verkürzungsosteotomie des Femurs durchgeführt werden. Nur so kann ohne ungebührlichen Druck der Femurkopf stabil reponiert werden. Hingegen sind wir mit pfannendachplastischen Eingriffen zum Zeitpunkt der Reposition eher zurückhaltend. Bei Kindern unter 2 Jahren lohnt es sich, die Pfannenentwicklung vorerst abzuwarten und allenfalls später einen pfannendachplastischen Eingriff durchzuführen. Die Nachbehandlung erfolgt während 12 Wochen in einem Becken-Bein-Gips in Fettweis-Stellung, anschließend während weiteren 3 Monaten in einer Schiene. Als Komplikationen treten Reluxationen, Femurkopfnekrosen und persistierende Dysplasien der Gelenkpfanne auf.
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  • 25
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    Monatsschrift Kinderheilkunde 145 (1997), S. 729-733 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Otitis media acuta ; Komplikationen ; Akute Mastoiditis ; Chronische Mastoiditis ; Mastoidektomie ; Therapie ; Key words Otitis media ; Complications ; Acute mastoiditis ; Chronic mastoiditis ; Masked mastoiditis ; Mastoidectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Antibiotics have led to a substantial decrease in the number of infants developing acute mastoiditis from middle ear infection. However, subacute or chronic mastoiditis can still often be observed, causing a variety of intracranial and extracranial life threating complications. The clinical course, the causative organism, risc factors and the role of surgical therapy were studied in 59 patients with mastoiditis. Masked forms of mastoiditis outnumbered the acute disease 2 to 1. 15% had developed complications, 5% life threatening intracranial complications (Abb. 3). Mastoid surgery was employed in all cases. 7 (12%) children needed repeated surgery because of delayed healing or clinical deterioration. The previous surgery in those cases was found to be inappropriate. Nevertheless, children recovered without any additional morbidity from surgery. Diagnostic and therapeutic strategies are discussed to cope with the difficult problem of chronic mastoiditis, taking into account bacteriologic findings, risk factors and important diagnostic information.
    Notes: Zusammenfassung Die häufigste Komplikation der Otitis media ist die Mastoiditis. Trotz der Antibiotika entwickelt eine nicht zu vernachlässigende Anzahl von Kindern eine subakute, chronische Form der Mastoiditis, die mit den gleichen intra- und extrakranialen Komplikationen einhergehen kann. Es wird über 59 Kinder mit Mastoiditis berichtet, die klinischen Symptome, Keimspektrum, Antibiotikasensibilität und die aufgetretenen Komplikationen werden dargelegt. Bei allen Kindern wurde eine Mastoidektomie durchgeführt. Die diagnostischen und therapeutischen Probleme der chronischen Mastoiditis werden unter Einbeziehung der Risikofaktoren diskutiert.
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  • 26
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    Der Orthopäde 26 (1997), S. 327-335 
    ISSN: 1433-0431
    Keywords: Key words Acetabulum ; Radiographic assessment ; Indications for surgery ; Surgical technique ; Complications ; Schlüsselwörter Acetabulum ; Diagnostik ; Operationsindikation ; Operationstechnik ; Komplikationen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Acetabulumfrakturen sind fast zur Hälfte mit einem Polytrauma vergesellschaftet und in über 80 % der Fälle findet man zusätzliche Verletzungen. Das Operationsziel besteht in der anatomischen Wiederherstellung der Hüftpfanne und Stabilisierung der Fraktur durch Osteosynthese, so daß postoperativ auf jegliche zusätzliche äußere Fixation verzichtet werden kann. Eine penible klinische und radiologische Abklärung ist notwendig, um eine erfolgversprechende Operationsplanung durchführen zu können. In jedem Fall gehören zum Röntgenstandard neben der Beckenübersicht die Zielaufnahme der verletzten Hüfte sowie das Ala- und Obturatorbild. Mit diesen Aufnahmen läßt sich u. a. auch das zentrale Acetabulumsegment („Domfragment“) gut beurteilen. Von besonderer Wichtigkeit ist, die primäre traumabedingte Ischiadicusverletzung genau zu dokumentieren. Auf die Repositionsqualität hat der Operationszeitpunkt ganz erheblichen Einfluß. Die Operation sollte zum frühest möglichen Zeitpunkt durchgeführt und das taktische Vorgehen genau geplant werden. Dabei sind besonders bei komplexen Frakturen und für die Wahl des Zugangs 3D-Rekonstruktionen sehr hilfreich. Ohne Repositionshilfen ist das Operationsziel in vielen Fällen nicht zu erreichen. Als Implantate kommen die vorgebogenen Rekonstruktionsplatten der AO, aber auch gerade Platten in Frage. Die Operationen verlangen große Erfahrung. Behandlungsbedingte Komplikationen sind Nervenschäden, mangelhafte Repositionen, fehlplazierte Implantate, instabile Montagen, Reluxationen u. a. Postoperative Wundinfektionen sind bei Beachtung einer lückenlosen Asepsis niedrig. Dagegen findet man nach ausgedehnten Zugängen oft metaplastische Ossifikationen, die nur bei starker Ausbildung (Brooker III und IV) die Funktion des Hüftgelenks beeinträchtigen. Eine präventive Medikation mit Indometacin ist immer angezeigt. Die generelle Röntgenbestrahlung ist abzulehnen.
    Notes: Summary Almost 50 % of acetabular fractures occur in polytraumatized patients; in over 80 % additional injuries are found. The surgical goal is anatomical restoration of the acetabulum and stable fixation, in order to avoid postoperative external fixation. Careful clinical and radiological evaluation is essential to successful surgery. Standard radiological investigations include an anteroposterior view of the pelvis, a “spot” radiograph of the affected hip as well as obturator and iliac oblique views. The latter arc is especially helpful in assessing the central segment of the acetabulum (“dome fragment”). The documentation of any primarily traumatic sciatic nerve lesion is very important, and the quality of reduction depends greatly on the timing of surgery. The operation should be performed as early as possible after the surgical procedure has been carefully planned. A 3-D CT scan provides good information in choosing the surgical approach for complex fractures. In most cases, adequate reduction cannot be accomplished without appropriate aids. For internal fixation, both curved ASIF plates and straight plates are used. The operation demands a high degree of experience. Postoperative complications include iatrogenic nerve palsy, insufficient reduction, incorrectly placed implants, unstable fixation, redislocation, etc. With scrupulous aseptic conditions, the postoperative wound infection rate is low. Ectopic bone formation can occur after extensive surgical approaches and may, depending on size (Brooker III and IV), impair the range of motion of the hip. Indometacin given perioperatively is always indicated. Postoperative radiation treatment should as a rule be viewed critically.
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  • 27
    ISSN: 1433-2981
    Keywords: Peripheral blood ; Progenitor cells ; Rat ; Stem cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The assay system for determination of haemopoietic progenitors in peripheral blood of rats is essen tial for potential studies on mobilisation and transplantation of circulating progenitor cells in a rat experimental model. This paper demonstrates the possibility of detection and quantification of pluripotent progenitors (Colony Forming Units-Spleen day 8-CFU-Sd8) and committed progenitors (Colony Forming Units Granulocyte Macrophage-CFU-GM and Burst Forming Units-Erythroid-BFU-E) in peripheral blood of rats in a steady state. For determination of CFU-Sd8 the ‘rat to mouse’ in vivo assay was used, and for committed progenitors in vitro assays on methylcellulose were employed. The CFU-Sd8 incidence ranged from 7.3 to 11.6/ml of rat blood, similar to that reported in literature for mice. The incidence of CFU-GM was found to be 59.7 ± 9.4/ml which is in the range of the literature data for mice, rabbits, dogs and humans. The incidence of BFU-E in rat peripheral blood was 4.3 ± 1/ml, which was relatively low, but could be also considered as comparable with some literature data for dogs and humans. The CFU-E were not detected by the technique used. These results confirmed the existence of circulatory blood pluripotent progenitors (CFU-Sd8) and committed (CFU-GM and BFU-E) progenitors in rat, as has been established for some other mammalian species.
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  • 28
    ISSN: 1434-0879
    Keywords: BBN ; Bladder tumor ; Rat ; Endoscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent advances in tumor carbohydrate biochemistry have demonstrated antitumor effects of locally administered GM3 ganglioside on mouse MBT-2 tumor. When intravesical therapy inN-butyl-N(4-hydroxybu-tyl)nitrosamine (BBN)-induced rat bladder tumor is attempted, it is essential to identify the tumor, to classify its size before therapy and to monitor the effect of the therapy. To establish a more reliable experimental therapeutic system, we assessed the development of BBN-induced rat bladder tumor by endoscopic observation. BBN-induced bladder tumors in rats were observed serially using a 4.2-F flexible fiberscope. The endoscopic findings were compared with the histopathological findings. Intravesical tumor growth varied greatly between individual rats. The smallest change detected by endoscopy was a small edematous lesion histologically proved to be papilloma. The largest nodular lesion was determined to be a papillary, transitional cell carcinoma. This noninvasive method makes the BBN rat experimental system more reliable by allowing confirmation of tumor formation and classification of the tumor volume prior to therapy.
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  • 29
    ISSN: 1434-0879
    Keywords: Renal cell carcinoma ; Renal tubular transport ; Renal cortical slices ; p-Aminohippurate ; Human ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In vitro accumulation ofp-aminohippurate (PAH) was investigated in “intact” human renal cortical slices of normal kidney tissue and in tissue slices of renal cell carcinoma (RCC). The technique used was established in preliminary experiments on rat kidney tissue slices. In principle, the accumulation capacity is comparable in renal tissue slices of both species (slice to medium accumulation ratios between 4 and 8). In man sex differences in accumulation capacity do not exist. But, as shown in detail for rats, accumulation capacity drops with age. Tissue slices of RCC are unable to accumulate PAH actively; slice to medium ratio reaches about 1 and indicates passive PAH uptake only. Surprisingly, in tumors of stage pTl PAH uptake is lowest, perhaps as a sign of PAH transport out of the cells. There is no difference between peripheral and central parts of RCC. Age and sex are without influence on PAH uptake in RCC tissue slices. Interestingly, the accumulation capacity of “intact” tissue of kidneys infested with RCC also depends on the severity of the tumor (stage, diameter), but not on grading and formation of metastases.
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  • 30
    Electronic Resource
    Electronic Resource
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    Urological research 25 (1997), S. 173-177 
    ISSN: 1434-0879
    Keywords: αB crystallin ; Heat shock protein ; Rat ; Kidney neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of two small stress proteins, αB crystallin and the 27-kDa heat shock protein (HSP27), was studied quantitatively and immunohistochemically in normal kidney and renal tumors in rats. Levels of αB crystallin in renal cell tumors tended to be higher than in normal kidney (P = 0.07), but with a wide range of values, whereas they were significantly lower in mesenchymal tumors (P 〈 0.0001). In contrast, HSP27 concentrations in both renal cell (mean ± SD: 1790 ± 940 ng/mg protein,n = 15) and mesenchymal (1260 ± 1080 ng/mg protein,n = 10) tumors were significantly higher than the normal kidney value (142 ± 30 ng/mg protein,n = 10,P 〈 0.0001). A positive correlation was found between αB crystallin and HSP27 levels limited to the renal cell tumor case (Pearson's correlation coefficient,r = 0.68,P 〈 0.01). Immunohistochemistry revealed the loops of Henle to be positive for αB crystallin, whereas HSP27 staining was positive in glomerular and interstitial vascular walls and epithelial cells of proximal and distal tubules. Positive immunostaining for αB crystallin was demonstrated in six of nine renal cell tumors (67%) studied and for HSP27 in all of the nine cases (100%).
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  • 31
    ISSN: 0942-0940
    Keywords: Rat ; brain injury ; diffuse injury ; free radicals ; lipid peroxidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Free radicals are generated after head injury. These radicals rapidly react with polyunsaturated fatty acids in the cell membrane and cause membrane destruction. This process is called lipid per-oxidation. Malondialdehyde (MDA) is one of the end products of lipid peroxidation, and it is a frequently used indicator of lipid per-oxidation in biological tissues. Using a diffuse head injury animal model, we studied the time course of lipid peroxidation in different regions of injured rat brains. In the present study, the MDA levels were 36.7%, 41.8%, and 35.1% greater than sham at one hour after injury at the frontal, parietal, and brain stem, respectively (p〈0.0001). The MDA levels in these regions continued to increase and peaked a 4 hours after the injury. The levels slowly decreased, and by 24 hours, they were still significantly higher than the sham control's. The elevation of MDA levels was less in the striatum and the temporal regions at one hour. They were 16.9% and 13.3%, respectively (p〈0.002). The MDA levels in these two regions continued to increase even after 4 hours of injury, but the degree of elevation never exceeded 35%. The results demonstrate that there is an immediate, posttraumatic burst of MDA production, suggesting the formation of free radicals after diffuse head injury. Even though all the regions sampled show the same effect, certain regions are less affected by this diffuse head injury animal model.
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  • 32
    ISSN: 1432-0533
    Keywords: Key words Schwann cell ; Diabetic neuropathy ; Human ; Animal model ; Galactose ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Despite early descriptions of hypertrophic Schwann cells and onion-bulb formation in patients with diabetic neuropathy, clinical and experimental studies have emphasized axonal pathology. In recent years, the Schwann cell has been further implicated in diabetic neuropathy because it is the primary intrafascicular location for the first enzyme of the polyol pathway, aldose reductase, which appears to have a role in modulating a variety of complications of diabetes, including diabetic neuropathy. To further explore the role of polyol pathway flux in the pathogenesis of Schwann cell injury, ultrastructural abnormalities of Schwann cells in human diabetic neuropathy (HDN) were compared with those in experimental galactose neuropathy (EGN), a well-characterized model of hyperglycemia without hypoinsulinemia. Similar to previous studies of EGN, reactive, degenerative and proliferative changes of Schwann cells were observed after 2, 4 and 24 months of galactose intoxication. Reactive changes included accumulation of lipid droplets, π granules of Reich and glycogen granules, increased numbers of subplasmalemmal vesicles, cytoplasmic expansion, and capping. Degenerative changes included enlargement of mitochondria and effacement of cristae, and disintegration of both abaxonal and adaxonal cytosol and organelles. Both demyelination and onion-bulb formation were seen at all time points, although supernumerary Schwann cells and axonal degeneration were most numerous after 24 months of galactose feeding. In sural nerve biopsy samples from patients with diabetes and progressive worsening of neuropathy, ultrastructural abnormalities in Schwann cells encompassed the full range of reactive, degenerative and proliferative changes described in galactose-fed rats. The concordance of fine-structural observations in nerves from galactose-fed rats and these adult-onset diabetic patients emphasizes the role of flux through aldose reductase in the complex pathology of diabetic neuropathy and points to the utility of galactose intoxication in helping to understand this metabolic disorder.
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  • 33
    ISSN: 1432-0533
    Keywords: Key words Microwave irradiation ; Mobile telephony ; Blood-brain barrier ; Vasogenic edema ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the effects of global system for mobile communication (GSM) microwave exposure on the permeability of the blood-brain barrier using a calibrated microwave exposure system in the 900 MHz band. Rats were restrained in a carousel of circularly arranged plastic tubes and sham-exposed or microwave irradiated for a duration of 4 h at specific brain absorption rates (SAR) ranging from 0.3 to 7.5 W/kg. The extravasation of proteins was assessed either at the end of exposure or 7 days later in three to five coronal brain slices by immunohistochemical staining of serum albumin. As a positive control two rats were subjected to cold injury. In the brains of freely moving control rats (n = 20) only one spot of extravasated serum albumin could be detected in one animal. In the sham-exposed control group (n = 20) three animals exhibited a total of 4 extravasations. In animals irradiated for 4 h at SAR of 0.3, 1.5 and 7.5 W/kg (n = 20 in each group) five out of the ten animals of each group killed at the end of the exposure showed 7, 6 and 14 extravasations, respectively. In the ten animals of each group killed 7 days after exposure, the total number of extravasations was 2, 0 and 1, respectively. The increase in serum albumin extravasations after microwave exposure reached significance only in the group exposed to the highest SAR of 7.5 W/kg but not at the lower intensities. Histological injury was not observed in any of the examined brains. Compared to other pathological conditions with increased blood-brain barrier permeability such as cold injury, the here observed serum albumin extravasations are very modest and, moreover, reversible. Microwave exposure in the frequency and intensity range of mobile telephony is unlikely to produce pathologically significant changes of the blood-brain barrier permeability.
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  • 34
    ISSN: 1432-0533
    Keywords: Key words Traumatic brain injury ; Hypothermia ; Fluid percussion ; Rat ; Contusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Early outcome measures of experimental traumatic brain injury (TBI) are useful for characterizing the traumatic severity as well as for clarifying the pathomechanisms underlying patterns of neuronal vulnerability. However, it is increasingly apparent that acute outcome measures may not always be accurate predictors of chronic outcome, particularly when assessing the efficacy of potential therapeutic regimens. This study examined the chronic histopathological outcome in rats 8 weeks following fluid-percussive TBI coupled with moderate post-traumatic brain hypothermia, a protocol that provides acute neuronal protection. Animals received a moderate parasagittal percussive head injury (2.01–2.38 atm) or sham procedure followed immediately by 3 h of brain hypothermia (30°C) or normothermia (37°C). Eight weeks following TBI, serial tissue sections were stained with hematoxylin and eosin or immunostained for glial fibrillary acidic protein. Tissue damage, gliosis and immunoreactive astrocytes were observed in the ipsilateral thalamus, hippocampus, and in the neocortex lateral to the injury site. Within the thalamus, focal necrosis was restricted to selective thalamic nuclei. Significant hippocampal cell loss was found in the ipsilateral dentate hilar region of both TBI groups. Quantitative volume measurements revealed significant decreases in cortical, thalamic and hippocampal volume ipsilateral to the impact in both TBI groups. Lateral ventricles were substantially enlarged in the TBI-normothermia group, an effect which was significantly attenuated by post-TBI hypothermia. The attenuation of lateral ventricular dilation by post-traumatic hypothermia is indicative of chronic neuroprotection in this TBI model. These data provide new information concerning the chronic histopathological consequence of experimental TBI and the relevance of this trauma model to chronic human head injury.
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  • 35
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    Der Anaesthesist 46 (1997), S. 38-42 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Spinalanästhesie ; Komplikationen ; Spinalkatheter ; Key words Spinal anaesthesia ; Complications ; Spinal catheter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Life-threatening cardiovascular complications are a serious risk even for healthy patients during spinal/epidural anaesthesia. The incidence of fatal cardiovascular complications for epidural anaesthesia is 1:10000, for spinal anaesthesia 1:7000. In contrast, general anaesthesia has an overall mortality of only 1:28000. Administration of IV fluids to minimise the haemodynaemic reactions of beginning sympatholysis is not always sufficient. In this study, we examined whether fractionated application of local anaesthetics via a spinal catheter would provide better haemodynamic stability. Methods: In a prospective study, we examined the haemodynaemic reactions of 300 patients during single-dose (n=150) versus continuous spinal anaesthesia (CSA) (n=150). Isobaric bupivacaine 0.5% was given through a 29 G Quincke needle (3.5 ml) or a 28 G spinal catheter (1.5 ml as a bolus, followed by 1 ml/10 min until an anaesthetic level of T12 was reached). Results: The sensory and motor effects of both methods were comparable. The T12 level of anaesthesia was achieved with the single-dose method after 10.5 min and with the continuous method after 19.1 min. After single-dose anaesthesia, the blood pressure dropped by 16.5% and the heart rate by 12% compared to the control values. During CSA no significant blood pressure changes were recorded; the heart rate decreased by 8%. In 15 cases vasoconstrictors had to be given to stabilise the lowered blood pressure after single-dose anaesthesia. Conclusion: With the use of CSA, the haemodynamic effects of sympatholysis can be minimised. This method thus has advantages, especially for high-risk cardiovascular patients.
    Notes: In dieser Arbeit sollte untersucht werden, ob die fraktionierte Lokalanästhetikaapplikation über einen Spinalkatheter zu einem stabileren Kreislaufverhalten beitragen kann. In einer prospektiv angelegten Studie wurde das Kreislaufverhalten von 300 Patienten unter einer Single-dose-Spinalanästhesie (n=150) und einer kontinuierlichen Spinalanästhesie (n=150) untersucht. Zur Anästhesie wurde isobares Bupivacain 0,5% verwendet, das über eine 29 G Quincke-Nadel (3,5 ml) oder einen 28 G Spinalkatheter (1,5 ml im Bolus, dann fraktioniert 1 ml/10 min bis zu einem Anästhesieniveau Th 12) gegeben wurde. Die sensible und motorische Qualität beider Verfahren war vergleichbar, das angestrebte Analgesieniveau Th 12 wurde unter der Single-dose-Spinalanästhesie nach 10,5 min erreicht, bei der kontinuierlichen Spinalanästhesie nach 19,1 min. Unter der Single-dose-Spinalanästhesie zeigte sich ein Abfall des Blutdrucks um 16,5% zum Ausgangswert und ein Abfall der Herzfrequenz um 12%. In 15 Verläufen mußten Vasokonstriktoren gegeben werden, um den Blutdruckabfall zu stabilisieren. Bei der kontinuierlichen Spinalanästhesie zeigten sich keine signifikanten Änderungen des Blutdrucks, die Herzfrequenz nahm um 8% ab. Mit der kontinuierlichen Spinalanästhesie werden die Auswirkungen der Sympathikolyse auf die Hämodynamik minimiert. Dieses Verfahren bietet daher bei kardiovaskulären Risikopatienten Vorteile gegenüber der einzeitigen Spinalanästhesie.
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  • 36
    ISSN: 1432-0533
    Keywords: Key words Intercellular adhesion molecule 1 ; Immunohistochemistry ; Rat ; Brain ; Trauma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A study was made on the expression of the intercellular adhesion molecule 1 (ICAM-1) in cerebral microvessels after cortical contusion trauma of the rat brain. The trauma was produced by a free-falling weight on the exposed dura of one fronto-parietal lobe. Immunohistochemistry was done on cryostat sections using a monoclonal antibody and the reaction product was visualized using the avidin-biotin-peroxidase complex method. Control and sham-operated rats showed immunostaining of some penetrating arteries of the cerebral cortex, the epithelial cells of the choroid plexus and occasional microvessels of the brain parenchyma. The same pattern of immunostaining was seen in rats that were subjected to trauma and killed after 30 min. All rats with contusion trauma that were allowed to survive for 6–72 h showed a substantial increase in the number of immunostained capillaries throughout the site of the lesion. The ipsilateral hippocampus showed a mild to moderate increase in the number of immunostained microvascular profiles. This phenomenon was also present in the lateral thalamus of some rats. The staining was seen as an uninterrupted line at the position of the endothelial cells, indicating an up-regulation of this adhesion molecule after brain trauma. Up-regulation of ICAM-1 is a well-known phenomenon in inflammatory and ischemic lesions of the brain but has not previously been described in detail in traumatic brain injury. ICAM-1 may be involved in the production of several post-traumatic events such as leukocyte adhesion, microcirculatory disturbances and edema formation.
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  • 37
    ISSN: 1432-0533
    Keywords: Key words Parkinson’s disease ; Neural transplantation ; Allogeneic ; Major histocompatibility complex antigens ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neural transplantation, as a therapeutic approach to Parkinson’s disease, still requires allogeneic graft material and raises questions of immunosuppression and graft rejection. The present study investigated the time course of major histocompatibility complex (MHC) expression and astrocytic response in allogeneic dopaminergic grafts, comparing two different grafting protocols. Adult 6-hydroxydopamine-lesioned Lewis 1.W rats received intrastriatal cell suspension grafts from the ventral mesencephalon of DA rat fetuses, either as single 1-μl macrograft via metal cannula or as four micrografts of 250 nl/deposit via a glass capillary. No immunosuppression was administered. Immunohistochemistry was performed at 1, 3, 6, and 12 weeks after grafting, using antibodies against donor- and host-specific MHC class I and II antigen, glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH). Most animals showed good allograft survival up to 12 weeks after transplantation with no signs of rejection. Reinnervation of the lesioned striatum by TH-positive neurites was observed from 3–6 weeks on. Expression of donor-specific MHC class I was comparably low in both allogeneic grafting groups, while host MHC class I and II reaction as well as astrocytic response tended to be higher in the macrografted animals. Donor MHC class II was not observed at any time point. It is concluded that intraparenchymal allografts of fetal mesencephalic cell suspensions can survive well in the rat Parkinson model without immunosuppression for at least 12 weeks, and that the expression of moderate amounts of donor-specific MHC class I antigen does not suffice to initiate a rejection process. In addition, the microtransplantation approach may reduce the level of trauma and subsequent MHC and GFAP expression and may, thereby, minimize the risk of graft rejection.
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  • 38
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    Der Anaesthesist 46 (1997), S. 697-703 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Ecstasy ; MDMA ; Intoxikation ; Komplikationen ; Key words Ecstasy ; MDMA ; Intoxication ; Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The increased consumption of ”ecstasy” (MDMA, 3,4-methylenedioxy-methamphetamine) has also increased the number of life-threatening intoxications. From a Medline search of the years 1992–1996, reports were registered and evaluated. Besides cerebral, cardiorespiratory, renal, and hepatic symptoms, hyperthermia syndromes such as malignant hyperthermia, neuroleptic malignant syndrome, or the serotonin syndrome were common. In addition to a discussion of the intoxication symptoms and their acute and intensive-care therapy, the psychological and physiological effects of ”ecstasy” will be described. Some historical considerations of the topic are included in this review.
    Notes: Zusammenfassung Die Zunahme des „Ecstasy”-Konsums (MDMA, 3,4-Methylendioxymethamphetamin) erhöhte ebenfalls die Anzahl lebensbedrohlicher Intoxikationen. Aus einer Medline-Recherche der Jahre 1992–1996 wurden Berichte über Intoxikationen erfaßt und ausgewertet. Intoxikation mit Ecstasy: Im Vordergrund steht neben zerebralen, kardiopulmonalen, renalen und hepatischen Symptomen auch das Hyperthermie-Syndrom im Sinne einer malignen Hyperthermie, eines neuroleptischen malignen Syndroms oder eines Serotonin-Syndroms. Neben der Diskussion der Intoxikationssymptome und deren möglicher Akut- und Intensivtherapie werden psychische und physische Wirkungen von „Ecstasy” beschrieben und zur Vervollständigung des Themas eine kurze historische Betrachtung der Droge gegeben.
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  • 39
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    Anatomy and embryology 196 (1997), S. 417-426 
    ISSN: 1432-0568
    Keywords: Key words Neuronal plasticity ; Fiber growth ; Regeneration ; Rat ; CNS myelin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  After lesions in the central nervous system (CNS), the affected nerve fibers usually cannot regenerate and reconnect to their original target cells. One important reason for this failure to regenerate is the presence of neurite growth inhibitory molecules in the myelin sheath of central nerve fibers. Despite the absence of regeneration fiber growth can occur after CNS lesions from intact nerve fibers unaffected by the lesion. These fibers can form new collaterals and sprout into the region denervated by the lesion, thereby increasing their terminal arbors in a process called collateral sprouting. A certain functional compensation for the nerve fibers lost by the lesion can be achieved by this mechanism. In the spinal cord, collateral sprouting is extensive after lesions in young postnatal animals and decreases with increasing age. In the spinal cord of adult animals, axon sprouting can be observed but is strongly restricted. The factors that determine the amount of sprouting found after lesions at different ages are still largely unknown. Recent evidence suggests that the myelin-associated neurite growth inhibitors that suppress regeneration also restrict collateral sprouting in the spinal cord. In addition, the expression of growth-associated molecules, in particular the growth-associated protein GAP-43, by the sprouting nerve fibers appears to be an important determinant of the sprouting response. The robustness of the sprouting response is thus likely to be controlled by intrinsic growth determinants of the sprouting neuron as well as by the growth promoting and growth inhibitory properties of the microenvironment of the sprouting fibers.
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  • 40
    ISSN: 1432-1238
    Keywords: Key words Cardiac output ; Complications ; Cost ; Dopexamine ; High risk patients ; Intensive care ; Morbidity ; Mortality ; Oxygen delivery ; Resource use ; Surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To investigate the cost implications of a treatment policy of a deliberate perioperative increase of oxygen delivery in high risk surgical patients. Design: A cost-effectiveness analysis comparing ‘protocol’ high risk surgical patients in whom oxygen delivery was specifically targeted towards 600 ml/min/m2 with ‘control’ patients. Interventions: In a randomised, controlled clinical trial we previously demonstrated a significant reduction in mortality (5.7% vs 22.2%, p=0.015) and morbidity (0.68±0.16 complications vs 1.35±0.20, p=0.008) in ‘protocol’ high risk surgical patients in whom oxygen delivery was specifically targeted towards 600 ml/min per m2 compared with ‘control’ patients. This current study retrospectively analysed the medical care and National Health Service resource use of each patient in the trial. Departmental purchasing records and business managers were consulted to identify M28.9nthe unit cost of these resources, and thereby the cost of treating each patient was calculated. Results: The median cost of treating a protocol patient was lower than for a control patient (£6,525 vs £7,784) and this reduction was due mainly to a decrease in the cost of treating postoperative complications (median £213 vs £668). The cost of obtaining a survivor was 31% lower in the protocol group. Conclusion: Perioperative increase of oxygen delivery in high risk surgical patients not only improves survival, but also provides an actual and relative cost saving. This may have important implications for the management of these patients and the funding of intensive care.
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  • 41
    ISSN: 1432-1238
    Keywords: Key words Viral pneumonia ; Immunosuppression ; Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pneumonia caused by herpes simplex virus type 1 (HSV1) is rare and occurs in severely immunosuppressed patients. HSV1 can be detected in bronchoalveolar lavage (BAL) from patients presenting with respiratory failure, but its direct effect on disease is difficult to prove. We demonstrate the causative role of HSV1 in the case of a 44-year-old male with Crohn's disease who presented to the intensive care unit with the acute respiratory distress syndrome after surgery. BAL cells were cultured and immunofluorescence confirmed the presence of HSV1 during the first weeks of illness. Increased IgG titers confirmed the diagnosis of a recurrent HSV1 infection. A lung biposy specimen showed fibroproliferation without pathogens. Immunosuppressive therapy had been stopped and acyclovir was introduced at this time. The diagnostic difficulties in this patient underline the importance of early recognition of viral infection as a potential cause of severe pneumonia in severely ill, immunocompromised patients.
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  • 42
    ISSN: 1432-1084
    Keywords: Key words: Bile ducts ; Neoplasms ; Interventional procedure ; Implantation metastasis ; Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Percutaneous transhepatic biliary drainage (PTBD) is the basis for most biliary interventional procedures. We recently observed the occurrence of a subcutaneous implantation metastasis after PTBD in a patient with incurable cholangiocarcinoma. Although tumor cell seeding along the catheter tract is a very rare complication, we think that PTBD should be avoided when curative resection is planned.
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  • 43
    ISSN: 1432-1106
    Keywords: Transplant ; Striatum ; Substantia nigra ; Patch-matrix ; Regeneration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract When patients with Parkinson’s disease initially show symptoms, approximately 80–85% of their dopaminergic nerve fibers in the striatum have degenerated. It is thus of importance to develop strategies to try to rescue the remaining dopaminergic neurons and to stimulate them to induce sprouting. In this study the goal was to examine whether the different subgroups of dopaminergic neurons in the ventral mesencephalon projecting to the basal ganglia have different sprouting capacities when stimulated by the trophic effect of a fetal striatal graft. Lateral ganglionic eminence was implanted into the lateral ventricle, the midportion of dorsal striatum, globus pallidus, or ventral striatum. Solid tissue pieces from 13- to 15-mm fetuses were stereotactically implanted into adult female Sprague-Dawley rats. At postgrafting week 4 the animals were perfused and processed for tyrosine hydroxylase (TH) immunohistochemistry. Transplants placed in the lateral ventricle were TH-negative, except for two cases with TH-positive fibers where the ependymal layer was disrupted, thereby allowing direct contact between the graft and the adjacent host striatum. The transplants placed into dorsal striatum were innervated by small patches of dopaminergic nerve fibers. Areas between the TH-positive patchy structures remained TH-negative. In grafts placed into globus pallidus, both patchy structures and a less dense TH-positive nerve fiber network was noted. The TH-positive growth pattern in transplants placed in ventral striatum was also devided into patchy and widespread growth. Grafts placed in globus pallidus and ventral striatum revealed significantly larger areas of TH-positive innervation compared with that measured in grafts placed in dorsal striatum and the lateral ventricle. In conclusion, it is possible to induce sprouting of TH-immunoreactive nerve fibers from all areas examined. The most potent areas to initiate dopaminergic growth were the globus pallidus and ventral striatum, where both a patchy dense and a widespread, less dense growth was induced. Thus, if using a trophic stimulus to induce sprouting from remaining dopaminergic nerve fibers in Parkinson’s disease, the preferential target to induce sprouting would be ventromedial striatum and growth would be guided toward dorsal striatum owing to the enhanced dopaminergic growth properties in the ventromedial areas.
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  • 44
    ISSN: 1432-1106
    Keywords: GABA ; Double immunostaining ; Retrograde tracing ; Diagonal band ; Disinhibition ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the septal complex, both parvalbumin and calbindin neurons cocontain GABA. In the same area, a large number of GABA-GABA synaptic connections can be observed. In order to further characterize their neurochemical nature, as well as the extrinsic and/or intrinsic origin of these GABA terminals, the following experiments were performed: (1) correlated light- and electronmicroscopic double immunostaining for calbindin and parvalbumin on septal sections of control rats; (2) light microscopic parvalbumin immunostaining of septal sections after surgical isolation (5 days) of the septum from its telencephalic or (3) hypothalamic afferents; and (4) parvalbumin immunostaining of sections prepared from the entire brain 2 days following horseradish peroxidase injection into the border between the lateral and medial septum. The results demonstrated that: (1) in a well-circumscribed, vertically longitudinal area located between the lateral and medial septum, 0.1–0.6 mm anterior to the bregma, a group of calbindin-containing, nonsomatospiny neurons are surrounded by parvalbumin-immunoreactive baskets; (2) these basket-forming axon terminals establish symmetric synaptic contacts with their targets; and (3) their cells of origin are not in the medial septum, but in the angular porition of the vertical limb. These observations indicate that a portion of the septal complex GABA-GABA synaptic connections represent functional interaction between two different types of GABAergic neurons. The presynaptic GABAergic neurons contain parvalbumin, and the postsynaptic GABAergic cells are immunoreactive for calbindin. Furthermore, a population of the medial septum/diagonal band parvalbumin neurons promect only to the hippocampus, while others, which may also send axons to the hippocampus, terminate on lateral septum calbindin cells as well.
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  • 45
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    Experimental brain research 113 (1997), S. 303-310 
    ISSN: 1432-1106
    Keywords: Hippocampus ; Adenosine A1 receptor ; DPCPX ; Purines ; Membrane partitioning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Despite its potent proconvulsant effects in vitro, the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) does not induce seizures when administered in vivo. This contrasts with the effects of less selective adenosine antagonists such as theophylline or cyclopentlytheophylline, and led us to reexamine the nature of DPCPX-induced epileptiform activity. In the present study, we report that proconvulsant effects of bath-applied DPCPX in rat hippocampal slices are only observed after a preceding stimulus such as NMDA receptor activation or brief tetanic stimulation. While this may be due to the absence of a basal “purinergic tone”, the relatively high interstitial concentrations of adenosine present in the slice suggest that access of the drug to A1 receptors may instead be prevented by tightly coupled endogenous adenosine, with the ternary adenosine-A1 receptor-G protein complex stabilised in the high-affinity conformation by a coupling cofactor. This implies that a substantial percentage of adenosine A1 receptors are inactive under physiological conditions, but that access of adenosine A1 receptor antagonists may be facilitated under pathological conditions. Once induced, DPCPX-evoked spiking persists for long periods of time. A “kindling” effect of A1 receptor blockade is unlikely, since persistent spiking is not usually observed with less selective A1 antagonists even after prolonged application. Alternatively, endogenous adenosine released during increased neuronal activity may activate A2 receptors during selective A1 blockade. The most important factor determining the duration of DPCPX-induced spiking, however, may be a persistence of the drug in the tissue and subsequent access to the A1 receptor via a membrane-delineated pathway, since DPCPX-induced spiking could be shown to decrease markedly after a transient superfusion of theophylline. This hypothesis, which implies that the apparent affinity of adenosine antagonists for the A1 receptor is in part a function of their membrane partitioning coefficient, is supported by a close correlation between alkylxanthine logP values obtained from the literature and theirK i value at A1 receptors, but not at the enzyme phosphodiesterase, whose xanthine binding site is presented to the cytosol. The implications for the therapeutic value of purinergic drugs are discussed.
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  • 46
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    Experimental brain research 113 (1997), S. 343-352 
    ISSN: 1432-1106
    Keywords: Memory ; Glutamate receptors ; GABA receptors ; Modulatory sites of NMDA receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Effects of redox reagents on excitatory and inhibitory synaptic responses as well as on the bidirectional plasticity of α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) andN-methyl-d-aspartate (NMDA) receptor-mediated synaptic responses were studied in CA1 pyramidal neurons in rat hippocampal slices. The oxidizing agent 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB, 200 μM) did not affect AMPA, GABAA or GABAB receptor-mediated synaptic responses or the activation of presynaptic metabotropic receptors. However, DTNB irreversibly decreased (by approximately 50%) currents evoked by focal application of NMDA. DTNB also decreased the NMDA component of the EPSC. The reversal potential of NMDA currents and the Mg2+ block were not modified. In the presence of physiological concentrations of Mg2+ (1.3 mM), DTNB did not affect the NMDA receptor-dependent induction of long-term potentiation (LTP) or long-term depression (LTD) expressed by AMPA receptors. In contrast, DTNB fully prevented LTP and LTD induced and expressed by NMDA receptors. Plasticity of NMDA receptor-mediated synaptic responses could be reinstated by the reducing agenttris-(2-carboxyethyl) phosphine (TCEP, 200 μM). These results suggest that persistent, bidirectional changes in synaptic currents mediated by NMDA receptors cannot be evoked when these receptors are in an oxidized state, whereas NMDA-dependent LTP and LTD are still expressed by AMPA receptors. Our observations raise the possibility of developing therapeutic agents that would prevent persistent excitotoxic enhancement of NMDA receptor-mediated events without blocking long-term modifications of AMPA receptor-mediated synaptic responses, thought to underlie memory processes.
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  • 47
    ISSN: 1432-1106
    Keywords: Key words Perinatal asphyxia ; Apoptosis ; Necrosis ; Hematoxylin-eosin ; DNA fragmentation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The consequences of perinatal asphyxia on the rat brain were studied 80 min to 8 days after birth with hematoxylin-eosin and in situ DNA double-strand-breaks labeling histochemistry. Asphyxia was induced by immersing fetus-containing uterus horns, removed from ready-to-deliver Sprague-Dawley rats, in a water bath at 37°C for various time periods (0–22 min). Spontaneous- and cesarean-delivered pups were used as controls. Perinatal asphyxia led to a decrease in the rate of survival, depending upon the length of the insult. No gross morphological changes could be seen in the brain of either control or asphyctic pups at any of the studied time points after delivery. However, in all groups, nuclear chromatin fragmentation, corresponding to in situ detection of DNA fragmentation, was observed at different stages. Nuclear fragmentation in control pups showed a specific distribution that appeared to be related to brain maturation, thus indicating programmed cell death. A progressive and delayed increase in nuclear fragmentation was found in asphyctic pups, which was dependent upon the length of the perinatal insult. The most evident effect was seen in frontal cortex, striatum, and cerebellum at postnatal day 8, although changes were also found in ventral-posterior thalamus, at days 1 and 2. Thus, nuclear chromatin fragmentation in asphyctic pups indicates a delayed post-asphyctic neuronal death. The absence of signs of inflammation or necrosis suggests that delayed neuronal cell death following perinatal asphyxia is an active, apoptosis-like phenomenon.
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  • 48
    ISSN: 1432-1106
    Keywords: Key words Entorhinal cortex ; Subiculum ; Retrohippocampus ; Latent inhibition ; Partial reinforcement extinction effect ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Experiment 1 assessed the effect of cytotoxic retrohippocampal (entorhinal and extra-subicular cortices) lesions on the development of latent inhibition (LI) using an off-the-baseline, between-subjects, conditioned emotional response paradigm. Sham-operated controls and unoperated rats that had been pre-exposed to a light stimulus prior to light-shock pairings showed less conditioned suppression towards the light stimulus than the nonpre-exposed animals, thus demonstrating LI. However, LI was not evident in rats with retrohippocampal lesions. In experiment 2, the same animals were trained to run in an straight runway for food. Half of the animals were trained under a 50% partial reinforcement schedule (i.e. they were rewarded randomly on half of the acquisition trials) and the other half were trained under a continuous reinforcement schedule (i.e. they were rewarded on every acquisition trial). When tested in extinction, animals trained on the partial reinforcement schedule showed greater persistence than animals trained on continuous reinforcement, thus demonstrating the partial reinforcement extinction effect (PREE). Rats with retrohippocampal lesions showed a PREE that was at least as clear as that seen in the sham-operated controls and in the unoperated animals. It is concluded that cytotoxic lesions of the retrohippocampal region selectively led to an abolition of LI, but spared the PREE. The present study thus provided evidence against the hypothesis that LI and the PREE share a common neural substrate.
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  • 49
    ISSN: 1432-1106
    Keywords: Key words Species differences ; CA2 ; Retrograde tracing ; Colocalization ; Theta rhythm ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Our recent studies showed the co-existence of substance P and calretinin in the supramammillo-hippocampal pathway of monkeys, as well as species differences in the synaptic targets of extrinsic substance P fibers in the hippocampi of monkeys and rats. Experiments used: (1) single and multiple stereotaxic injection of wheat germ agglutinin-conjugated HRP into the hippocampus and immunostaining for substance P in the supramammillary area; (2) colocalization of substance P and calretinin in supramammillary area cells; and (3) colocalization of these two neurochemicals in retrogradely labeled supramammillary projective cells of both male and female rats. These demonstrated: (a) many calretinin- and fewer substance P-immunoreactive neurons retrogradely labeled in the ipsilateral supramammillary area; (b) approximately 74% of all substance P cells contain calretinin and 9% of the calretinin neurons co-contain substance P; and, most importantly (c) none of the retrogradely labeled supramammillary cells colocalize calretinin and substance P. These results indicate the presence of two distinct supramammillo-hippocampal projections in the rat, one that contains substance P and the other calretinin. The latter innervates the same areas as those in the monkey, and the former terminates only in the CA2 hippocampal subfield.
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  • 50
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    Experimental brain research 115 (1997), S. 129-136 
    ISSN: 1432-1106
    Keywords: Key words Fos-like immunoreactivity ; Middle cerebral artery ; Focal cerebral ischaemia ; Spinal cord neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study examined c-fos protein expression in the brain and spinal cord of rats following permanent occlusion of the middle cerebral artery (MCA) above the rhinal fissure. At 1 h after right-sided MCA occlusion, Fos-like immunoreactivity (Fos-LI) was detected in neurons not only in the ipsilateral cerebral cortex but also in the spinal cord. In the latter, Fos-LI was localized in the nucleus and perikarya of neurons in the grey matter, notably the large motor neurons in the ventral horn. Fos-LI was most intense at 2–4 h, but became undetectable after 48 h in the cerebral cortex and 72 h in the spinal cord. In sham-operated animals, Fos-LI was almost undetectable or virtually absent. It was also not detected in the core territory supplied by the MCA at any time points after arterial occlusion. When the ischaemia-induced neuronal damage in both the cerebral cortex and spinal cord was evaluated by Nissl staining, some neurons appeared atrophic. We conclude that the induction of Fos-LI in neurons of the cerebral cortex and spinal cord is linked respectively to early onset–short stimulation and persistent excitatory or disinhibition phenomenon as a result of focal ischaemic brain injury.
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  • 51
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    Experimental brain research 113 (1997), S. 138-143 
    ISSN: 1432-1106
    Keywords: Parkinson’s disease ; Neural transplantation ; Cell death ; Lazaroid ; Dopamine ; Free radicals ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We explored the effects of congeners of nitrogen monoxide (NO) on cultured mesencephalic neurons. Sodium nitroprusside (SNP) was used as a donor of NO, the congeners of which have been found to exert either neurotoxic or neuroprotive effects depending on the surrounding redox milieu. In contrast to a previous report that suggests that the nitrosonium ion (NO+) is neuroprotective to cultured cortical neurons, we found that the nitrosonium ion reduces the survival of cultured dopamine neurons to 32% of control. There was a trend for further impairment of dopamine neuron survival, to only 7% of untreated control, when the cultures were treated with SNP plus ascorbate, i.e. when the nitric oxide radical (NO) had presumably been formed. We also evaluated the effects of an inhibitor of lipid peroxidation, the lazaroid U-83836E, against SNP toxicity. U-83836E exerted marked neuroprotective effects in both insult models. More than twice as many dopamine neurons (75% of control) survival when the lazaroid was added to SNP-treated cultures and the survival was increased eight-fold (to 55% of control) when U-83836E was added to cultures treated with SNP plus ascorbate. We conclude that the congeners of NO released by SNP are toxic to mesencephalic neurons in vitro and that the lazaroid U-83836E significantly increases the survival of dopamine neurons in situations where congeners of NO are generated.
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  • 52
    ISSN: 1432-1106
    Keywords: Antidiuretic hormone ; Osmotic stimulus ; Anteroventral third ventricular region ; Prostaglandins ; Meclofenamate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study explored the roles of prostaglandins in the anteroventral third ventricular region, a cerebral osmoreceptor site, in the osmoregulation mechanism of vasopressin release. We injected (1 μl) prostaglandin E2 (12.8 nmol) or meclofenamate (78.3 nmol), an inhibitor of prostaglandin biosynthesis, into the brain region or the lateral cerebral ventricle of conscious rats, examining their effects on plasma vasopressin and its controlling factors in the presence or absence of an osmotic stimulus. The injection of prostaglandin E2 into the anteroventral third ventricular region augmented plasma vasopressin and arterial pressure after 5 min and 15 min, without influencing plasma osmolality, sodium, potassium, or chloride. In contrast, intraventricular injection of prostaglandin E2 did not cause any significant effect on those variables. The i.v. infusion (0.1 ml·kg−1·min−1) of hypertonic saline (2.5 mol/l) enhanced plasma vasopressin after 15 min and 30 min; this was accompanied by increased plasma osmolality, sodium, and chloride, and by unaltered or elevated arterial pressure. Meclofenamate given into the anteroventral third ventricular region 30 min before starting the hypertonic saline infusion abolished the osmotic vasopressin response without significantly changing the responses of the other variables. Histological analysis showed that the injection sites of meclofenamate in these rats were close to those of prostaglandin E2 in the anteroventral third ventricular region and included the organum vasculosum of the lamina terminalis and the surrounding area, the medial preoptic area, and periventricular and median preoptic nuclei. When injection cannulae for meclofenamate deviated from those areas incidentally or when the drug was expressly administered into the cerebral ventricle, the osmotic vasopressin response was not inhibited. Plasma vasopressin and the other variables observed during the i.v. infusion of isotonic saline (0.15 mol/l) were not affected significantly by meclofenamate administration into the anteroventral third ventricular region or the cerebral ventricle. On the basis of these results, we concluded that prostaglandins synthesized in and/or near the anteroventral third ventricular region might contribute to the facilitation of vasopressin release in the hyperosmotic state.
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  • 53
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    Experimental brain research 114 (1997), S. 51-62 
    ISSN: 1432-1106
    Keywords: Key words Pupillary light reflex ; Pretectum ; Anterograde and retrograde tracing ; GABA immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The olivary pretectal nucleus is a primary visual centre, involved in the pupillary light reflex. In the present study an ultrastructural analysis was made of the olivary pretectal nucleus by means of separate, anterograde and retrograde tracing techniques and immunohistochemistry of gamma-aminobutyric acid. Large-projection neurons and two types of gamma-aminobutyric acid-immunoreactive (GABA-ir) neurons are observed in the olivary pretectal nucleus. The primary dendrites of the projection neurons have a dichotomous appearance, the secondary dendrites a multipolar appearance. At the ultrastructural level the projection neurons have well-developed Golgi fields, abundant rough endoplasmic reticulum and the nucleus is always heavily indented. Numerous small GABA-ir neurons and a few medium-sized GABA-ir neurons are found. The small GABA-ir neurons contain a few stacks of rough endoplasmic reticulum and the nucleus is oval-shaped. The medium-sized GABA-ir neurons have well-developed Golgi fields, a moderate number of rough endoplasmic reticulum stacks and an indented nucleus. GABA-positive dendritic profiles containing vesicles also are observed. In the neuropil of the olivary pretectal nucleus, retinal terminals are found that contain round clear vesicles and electron-lucent mitochondria. They make asymmetric synaptic contacts (Gray type I) with dendritic profiles and with profiles containing vesicles. Terminals originating from the contralateral olivary pretectal nucleus exhibit small, round clear vesicles, electron-dense mitochondria and make asymmetric synaptic contacts (Gray type I) mainly with dendritic profiles. Two types of GABA-ir terminals were found. One type is incorporated in glomerulus-like arrangements, whereas the other type is not. GABA-ir terminals contain pleomorphic vesicles, electron-dense mitochondria and make symmetric synaptic contacts (Gray type II). Retinal terminals, terminals originating from the contralateral olivary pretectal nucleus and GABA-ir terminals are organized in glomerulus-like structures, in which dendrites of the large projection neurons form the central elements. Triadic arrangements are observed in these structures; a retinal terminal contacts a dendrite and a GABA-ir terminal and the GABA-ir terminal also contacts the dendrite. The complexity of the synaptic organization and the abundancy of inhibitory elements in the olivary pretectal nucleus suggest that the olivary pretectal nucleus is strongly involved in processing visual information in the pupillary light reflex arc.
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  • 54
    ISSN: 1432-1106
    Keywords: Key words Fascia dentata ; Mossy cells ; Interneurons ; Lucifer yellow ; Phaseolus vulgaris leucoagglutinin ; Septohippocampal projection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Mossy cells in the hilus of the rat dentate gyrus are the main cells of origin of the dentate commissural and associational projections. They project along the septotemporal axis of the dentate gyrus and may thus influence the hippocampal signal flow in a longitudinal direction. To analyze the septal innervation of these hilar neurons, anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHAL) was used in combination with intracellular labeling of mossy cells (Lucifer yellow). Anterogradely labeled septal fibers impinge on proximal and distal dendrites of hilar mossy cells but spare the cell body. In contrast, numerous aspiny hilar neurons, presumably GABAergic interneurons, receive a septal innervation on their somata and proximal primary dendrites. These data demonstrate that septal fibers show a specificity for the dendritic segments of hilar mossy cells. Since mossy cells project predominantly to adjacent hippocampal lamellae, the activity of adjacent portions of the dentate gyrus may be influenced by the septal input onto these neurons.
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  • 55
    ISSN: 1432-1106
    Keywords: Key words Anionic surfactants ; Sodium dodecyl sulphate ; Blood-brain barrier ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The blood-brain barrier (BBB) arises from epithelial-like tight junctions that virtually cement adjoining capillary endothelium together in the brain microvascolature. Several experimental manipulations have been shown able to increase the permeability of brain capillaries, by altering endothelial cell membrane integrity or activating specific biochemical pathways involved in regulation of BBB functionality. Because of its amphiphilic nature, sodium dodecyl sulphate (an anionic surfactant widely used as solubilizer or stabilizer in several pharmaceutical preparations; SDS) may enter into interactions with the major membrane components, which are lipids and proteins. The aim of the present study was to determine the effect of an intracarotid infusion of SDS (25, 50 and 100 µg/kg; infusion rate: 3 ml/min for 30 s) on the functionality of the BBB in the rat. An extensive, dose-dependent Evans blue extravasation was observed, in the ipsilateral brain hemisphere, 15 min following SDS infusion. These results were confirmed by the significant increase in [14C]α-aminoisobutyric acid ([14C]AIB) transport (evaluated by calculating a unidirectional transfer constant, K i, for the tracer from blood to brain) measured in several ipsilateral brain regions 2 min after SDS infusion; this SDS-elicited BBB opening to [14C]AIB proved to be reversible. Since the BBB is created by the plasma membrane and tight junctions of the endothelial cells, the change in BBB permeability caused by SDS might be explained as a nonspecific surfactant-membrane interaction. Furthermore, SDS might affect the functional characteristics of brain vascular endothelial cells by an interaction with specific BBB proteins and/or biochemical pathways. In conclusion, one can suggest that intracarotid infusion of SDS might provide a useful clinical approach for the intentional introduction of different substances into the brain. On the other hand, these findings should call attention to possible dangerous consequences of using SDS as solubilizer in drug excipients.
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  • 56
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    Experimental brain research 116 (1997), S. 97-103 
    ISSN: 1432-1106
    Keywords: Key words Chronic constriction injury ; Infraorbital nerve ; Painful trigeminal neuropathy ; Heat-hyperalgesia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Secondary trigeminal neuralgia (STN) follows an injury to the trigeminal nerve or one of its branches. Although rare, this condition results in great suffering and it is notoriously difficult to treat. The experimental analysis of painful neuropathy due to damage to the innervation of the limbs (e.g., the sciatic nerve) has progressed rapidly in recent years, but very few reports have appeared concerning experimental neuropathy in the trigemenial region. We report here an experimental rat model of trigeminal neuropathic pain produced by a chronic constriction injury to the infraorbital nerve (CCI-ION), and on a method that detects heat-evoked pain-related behavior. Rats with the CCI-ION have clear signs of heat-hyperalgesia when stimulated on the snout (the vibrissal pad). The hyperalgesia is seen both ipsi- and contralateral to the side of nerve injury, but is significantly more severe ipsilaterally, and lasts about 12 days.
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  • 57
    ISSN: 1432-1106
    Keywords: Key words Hippocampus ; Learning ; Memory ; Recovery ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The monosialoganglioside GM1 is a compound with neurotrophic properties found to foster functional recovery in various paradigms of brain damage. The present experiment examined whether systemic treatment with GM1 may facilitate behavioral recovery in rats with fimbria-fornix lesions and intrahippocampal grafts rich in cholinergic neurons. Among 68 Long-Evans female rats, 46 sustained a bilateral electrolytic lesion of the fimbria and the dorsal fornix and 22 were sham-operated. Fourteen days later, half the lesioned rats were subjected to intrahippocampal grafts of a fetal septal cell suspension. Starting a few hours after lesion surgery and over a 2-month period, half the rats of each surgical treatment group received a daily injection of GM1 (30 mg/kg i.p.), the other half being injected with saline as a control. All rats were subsequently tested for locomotor activity and radial maze learning. The lesions induced locomotor hyperactivity and impaired learning performances in both an uninterrupted and an interrupted radial maze testing procedure. In all rats with surviving grafts, the grafts had provided the hippocampus with a new and dense organotypic acetylcholinesterase-positive innervation pattern which did not differ between saline- and GM1-treated subjects. The scores/performances of the rats that had received only the grafts or only the GM1 treatment did not differ significantly from those of their respective lesion-only counterparts. However, in the radial-arm maze task, the grafted rats given GM1 showed improved learning performances as compared with their saline-treated counterparts: they used more efficient visit patterns under the uninterrupted testing conditions and made fewer errors under the interrupted ones. The results suggest that GM1 treatment or intrahippocampal grafts used separately do not attenuate the lesion-induced behavioral deficits measured in this experiment. However, when GM1 treatment and grafts are used conjointly, both may interact in a manner allowing part of these deficits to be attenuated.
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  • 58
    ISSN: 1432-1106
    Keywords: Key words Amino acid immunocytochemistry ; Axon collateralization ; Thalamus ; Fluorescent tracers ; Limbic system ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Small, stereotaxically guided injections of true blue (TB) were made into the retrosplenial granular cortex (RSg) and of diamidino yellow (DY) into the dorsal portion of the rostral pole of the thalamic reticular nucleus (TRN) in 16 adult rats to determine whether axons projecting from the anterior thalamic nuclear complex (ATN) to the TRN are branches of axons also projecting to the RSg. Following injections of the fluorescent dyes, serial coronal sections of the brain revealed single retrogradely labelled, and large numbers of double retrogradely labelled neuronal cell bodies in the ipsilateral anteroventral and anterodorsal nuclei and smaller numbers in the anteromedial nucleus of the ATN complex. In a se- cond series of six adult rats with similar double injections of TB and DY, two sections in three were immunoreacted, one with antiserum against glutamate and one with antiserum against aspartate, using indirect immunofluorescence with rhodamine to detect reactive cells. The great majority of both single and double retrogradely labelled cell bodies were also immunoreactive for aspartate or glutamate. In addition, a moderate to small number of non-immunolabelled neurons projecting to the TRN and/or to the RSg were also found in all three nuclei of the ATN complex. These results are compatible with the possibility that large numbers of neurons in the ATN send axonal branches to both the RSg and the TRN, and that many such neurons use glutamate and/or aspartate as transmitters. The findings also suggest that the projections from the ATN might be heterogeneous with respect to transmitter phenotype.
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  • 59
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    Experimental brain research 117 (1997), S. 324-340 
    ISSN: 1432-1106
    Keywords: Key words Trigeminal nerve ; Mechanoreceptors ; Cutaneous sensory nerve ending ; Perivascular innervation ; Vibrissae ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It is well established that sensory perception becomes impaired with advancing age and that, in parallel, dystrophy and degeneration of axons occur in sensory pathways. In this study, the impact of aging was examined in the mystacial pad, which receives a large variety of sensory nerve endings organized in a highly predictable pattern. Mystacial pad specimens from aged (30 months old) and young adult (2–3 months old) female Sprague-Dawley rats were processed, in parallel, for immunohistochemical analyses with antibodies against human neuronal cytoplasmic protein (protein gene product 9.5), transmitter enzymes, and several neuropeptides. Several changes in cutaneous innervation including both degenerative and regenerative processes were evident in the aged rat: (1) the Merkel endings and lanceolate endings that emanate from large-caliber afferents in the whisker follicles were reduced and showed signs of degeneration. Furthermore, a reduction of piloneural complexes at the intervibrissal hairs were evident, but only in aged rats that showed more severe behavioral sensorimotor disturbances. In contrast, Ruffini endings as well as mechanoreceptors emanating from medium-caliber axons, i.e., transverse lanceolate and reticular endings, appeared normal. (2) A reduction was evident among two sets of unmyelinated epidermal endings; however, the epidermal innervation affiliated with the intervibrissal hairs appeared normal in the aged rat. (3) A loss of sympathetic neuropeptide tyrosine (NPY) or tyrosine hydroxylase-immunoreactive (IR) and somatosensory Calcitonin gene-related peptide (CGRP)-IR perivascular axons was paralleled by an increase in presumed parasympathetic NPY/CGRP-IR axons. (4) Two “novel” networks of fine-caliber axons were observed in the outer and inner root sheaths of the whisker follicles in the aged rat. (5) NPY was present in a population of small-caliber, somatosensory CGRP-IR axons in the aged rat. This may represent a de novo synthesis, since, normally, NPY-like immunoreactivity is not observed in this set of axons. Our results suggest that the sensory impairments occurring with advancing age are part of a peripheral process instigated by changes in nerve-target interactions and/or incapacitation of the neuronal machinery to sustain the axonal integrity.
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  • 60
    ISSN: 1432-1106
    Keywords: Key words “Central pain” ; Picrotoxin ; Epilepsy ; Acetylcholine ; Cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In this study, we examined the modulation by acetylcholine of electrocorticographical (ECoG) ictal events and spontaneous pain-like behaviors following cortical application of the GABAA antagonist picrotoxin in the awake rat. Distilled water as vehicle, the cholinomimetic substance eserine, and the general muscarinic antagonist atropine were microinjected 10 min before the second microinjection of 2 μg picrotoxin into the hind paw region of the somatomotor cortex (SmI). Under these conditions, we observed that eserine (physostigmine, 1 μg, 10 μg, and 20 μg) did not consistently modify the number of the picrotoxin-induced ECoG spikes and bursts, but instead produced a massive enhancement of the number of hind paw licks compared with vehicle at 10 μg and, to a lesser extent, the number of the stereotyped “turn-in” and “neglected” paws following picrotoxin. In contrast, atropine (l μg, 10 μg, and 20 μg) increased the number of the picrotoxin-induced spikes and bursts at 10 μg and, at all doses, decreased the number of the picrotoxin-induced pain-like symptoms. Statistically significant changes for the number of paw lifts, licks, and “turn-in” paws were observed only with 10 μg. These results tend to show that epilepsy and pain are not strictly related to each other and also emphasize the cortex as a target for interactions between GABA and acetylcholine relative to “central” pain.
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  • 61
    ISSN: 1432-1106
    Keywords: Key words Hippocampus ; Commissural fibers ; Reactive sprouting ; Synaptogenesis ; Synaptophysin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Expression of the synaptic vesicle protein synaptophysin was studied in lesion-induced sprouting neurons of the contralateral entorhinal cortex and in the contralateral dentate gyrus using immunocytochemistry at the light- and electron-microscopic level. Perikaryal immunoreactivity for synaptophysin was found between 8 and 10 days postlesion. Light microscopy revealed that synaptophysin immunostaining was present in almost all neurons of layers II and III of the contralateral medial entorhinal cortex. These neurons give rise to the sprouting, crossed temporodentate pathway. In addition, some hilar neurons of the contralateral dentate gyrus, which are the parent cells of sprouting commissural fibers, were immunostained for synaptophysin. Transient immunostaining for synaptophysin was observed within cell bodies and dendrites. Additionally, the cell bodies were outlined by immunoreactive puncta, identified by electron microscopy as nerve terminals. Our results revealed that sprouting neurons express the major synaptic vesicle protein synaptophysin during reactive synaptogenesis in a pattern that reflects biosynthesis and sorting of this protein as seen in developing neurons during synapse formation.
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  • 62
    ISSN: 1432-1106
    Keywords: Key words Locomotor recovery ; Neural transplantation ; Fictive locomotion ; Serotonin ; 6-Hydroxydopamine ; Zimelidine ; Rat ; Spinal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Locomotor movements are programmed in a specialised neuronal network that is localised in the central nervous system and referred to as the central pattern generator (CPG) for locomotion. This CPG can be activated by pharmacological agents such as monoamines. The aim of the present study was to try to activate the CPGs by using cells that are supposed to release serotonin locally. Adult chronic spinal rats were injected with embryonic brainstem neurons within the spinal cord under a thoracic transection. This procedure resulted in a monoaminergic reinnervation of the lumbar enlargement. With the help of a specific neurotoxin for noradrenergic neurons (6-hydroxydopamine), it was possible to isolate the serotonergic system. After such transplantation of monoaminergic neurons and even with serotonergic neurons alone, a bilateral, alternating, rhythmic locomotor-like activity recovered in hindlimbs. Furthermore, this locomotor-like activity was clearly facilitated when the re-uptake of serotonin was blocked by zimelidine. Therefore, we conclude that transplanted embryonic serotonergic neurons are able to activate the CPG for locomotion.
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  • 63
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    Experimental brain research 113 (1997), S. 520-533 
    ISSN: 1432-1106
    Keywords: Key words Spinal Ia terminations ; Action potentials ; Baclofen ; Calcium influx ; Cat ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In the ventral horn of the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium, microelectrophoretically administered (–)-baclofen, but not (+)-baclofen, reversibly reduced the duration of the orthodromic action potential of muscle group Ia afferent terminations, but not those of muscle group I afferent myelinated fibres. The presumably submicromolar concentrations are already known to reversibly reduce excitatory transmitter release from muscle group Ia afferent terminations. Action potential durations were estimated from threshold recovery curves after an orthodromic impulse using an extracellular microstimulation technique. Both of these presynaptic effects of (–)-baclofen were blocked by baclofen antagonists, and neither appeared to be reduced by the potassium channel blocking agents tetraethylammonium and 4-aminopyridine. Tetraethylammonium and 4-aminopyridine also did not significantly modify the reduction by (–)-baclofen of monosynaptic field potentials in the lumbar cord of rats anaesthetised with pentobarbitone sodium. In the cat the maximum reduction by (–)-baclofen of termination action potentials was considerably less than that produced by cadmium ions, which, unlike (–)-baclofen, also reduced the action potential duration of group I myelinated fibres. These findings are consistent with a reduction by (–)-baclofen of the influx of calcium through voltage-activated channels in the membrane of group Ia terminations, a proposal which also accounts for the reduction by (–)-baclofen of the release of GABA at axo-axonic depolarizing synapses on these terminations. The results are discussed in relation to the mode of action of (–)-baclofen and the different sensitivities of transmitter release at various central synapses.
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  • 64
    ISSN: 1432-1106
    Keywords: Key words Forebrain ischemia ; Hyperglycemia ; Hippocampus ; Bioenergetic state ; Cyclosporin A ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A recent study from this laboratory has shown that brief transient ischemia (2 min 30 s) in normo- and hyperglycemic rats leads to moderate neuronal necrosis in CA1 cells of the hippocampus, of equal density in the two groups. However, hyperglycemic animals failed to depolarize during the ischemia, nor did they show a decrease in extracellular calcium concentration. The present study was undertaken to study the metabolic correlates to these unexpected findings. Normoglycemic (plasma glucose ∼6 mM) and hyperglycemic (∼20 mM) rats were subjected to ischemic periods of 1 min and 2 min 15 s (2 min 30 s with freezing delay considered), and their brains were frozen in situ. Samples of dorsal hippocampus were dissected at –22°C and extracted for the measurement of phosphocreatine (PCr), creatine, ATP, ADP, AMP, glucose, glycogen, and lactate. Normoglycemic animals showed rapid depletion of PCr, ATP, glucose, and glycogen, and a rise in lactate content to 10–12 mM·kg–1 during the ischemia. Hyperglycemic animals displayed a more moderate rate of fall of PCr and ATP, with ATP values exceeding 50% of control after 2 min 30 s. Glycogen stores were largely maintained, but degradation of glucose somewhat enhanced the lactic acidosis. The results demonstrate that hyperglycemic rats maintained ATP at levels sufficient to prevent cell depolarization and calcium influx during the ischemic period. However, the metabolic perturbation observed must have been responsible for the delayed neuronal damage. We speculate that lowered ATP, increased inorganic P, and oxidative stress triggered a delayed mitochondrial permeability transition (MPT), which led to delayed neuronal necrosis. This assumption was supported by a second series of experiments in which CA1 damage in hyperglycemic rats was prevented by cyclosporin A, a virtually specific inhibitor of the MPT.
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  • 65
    ISSN: 1432-1106
    Keywords: Key words Enkephalin ; GABA ; Basal ganglia ; 6-Hydroxydopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In Parkinson’s disease the dopaminergic nigrostriatal pathway degenerates, resulting in an imbalance in activity of two pathways of information flow through the basal ganglia. In animal models of the disease, the striatonigral pathway becomes underactive and the striatopallidal pathway becomes overactive. In the present study immunocytochemistry for enkephalin and GABA and anterograde labelling were used to investigate whether morphological plasticity occurs in striatopallidal terminals following unilateral removal of the nigrostriatal dopaminergic pathway. Pallidal terminals were immunostained to reveal enkephalin and examined in the electron microscope (n=399). Immunoreactive synaptic bouton profiles were on average 64% larger on the experimental side 26 days after the lesion. Analysis of their shape revealed that those on the dopamine-depleted side of the brain were more irregular in profile and that their synaptic specialisations were more complex in shape but not significantly different in length. Striatopallidal terminals were also identified by GABA immunocytochemistry combined with anterograde labelling (n=20). Double-labelled boutons were significantly larger in cross-sectional area on the experimental side (57%). Analysis of terminals that were simply labelled by the immunogold method to reveal GABA (n=278) showed no significant differences in size between terminals from the dopamine-depleted and control side. This suggests that a substantial number of GABAergic terminals in the globus pallidus do not belong to the striatopallidal population of terminals. These morphological changes correlate with previous studies suggesting striatopallidal boutons are more active after destruction of dopaminergic input to the neostriatum.
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  • 66
    ISSN: 1432-1238
    Keywords: Key words Central venous catheterization ; Venobronchial fistula ; Cardiac surgery ; Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Venobronchial fistula is a rare complication of long-term central venous catheterization. We present the uncommon occurrence of a venobronchial fistula as an acute complication of central venous catheterization during open heart surgery. The factors responsible for this unusual complication and the methods to prevent it are discussed.
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  • 67
    ISSN: 1432-1211
    Keywords: Key words CD4 ; Rat ; LEC ; thid ; Chromosomal mapping
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 68
    ISSN: 1432-1920
    Keywords: Key words Anterior cervical surgery ; Complications ; Infection ; Computed tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a 44-year-old woman who developed an atypical retro-oesophageal abscess 4 years after anterior cervical surgery with fusion (ACSF). She presented with dysphagia but no fever or definite laboratory signs of inflammation. Delayed or chronic dysphagia following Cloward's operation is usually related to graft displacement. Infection may also, more rarely, be encountered in conjunction with dysphagia, but is typically associated with a classical clinical presentation and laboratory results. We recommend that in cases of delayed dysphagia without evidence of graft migration, the possibility of retropharyngeal infection should be considered, even in the absence of clinical signs or supporting laboratory evidence. MRI in this rare delayed complication is nonspecific but suggestive, and hence represents the imaging modality of choice in such situations.
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  • 69
    ISSN: 1432-1920
    Keywords: Key words Angioplasty ; Intracranial artery ; Complications ; Restenosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purposes of this study were to determine the optimal time for initial follow-up angiography, the restenosis rate after successful intracranial percutaneous transluminal cerebral angioplasty (PTCBA), and finally to identify lesion-specific characteristics for predicting successful angioplasty. Thirty-five patients underwent PTCBA with follow-up angiography 3 and 12 months later. Although 27 lesions were adequately dilated, permanent complications occurred in 3 patients. The restenosis rate at 3 months was 29.6 %; patients without restenosis at 3 months remained free from vessel narrowing at 12 months. Restenosis occurred on severe, eccentric lesions, total occlusions or extremely angulated lesions. There was a strong correlation between sufficient dilatation and lower re- stenosis rate, and concentric and short lesions (type A). We conclude that the optimal time for initial angiographic follow-up is 3 months after PTCBA. PTCBA is most suitable for type A lesions with higher success, lower morbidity and lower restenosis rates.
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  • 70
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    Neuroradiology 39 (1997), S. 282-285 
    ISSN: 1432-1920
    Keywords: Key words Intervertebral disc ; hernia ; Nucleotomy ; Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We reviewed the records of 243 patients treated at 271 disc levels to determine the incidence of side effects and complications of percutaneous nucleotomy. In our early experience there were 7 technical failures (2.5 % of all attempts), of which 6 were at the 5th disc level. The success rate dropped from 67 % at 3 months to 60 % 1 year after treatment due to recurrences in 16 patients (6.6 %). Extruded or sequestered fragments were found in 6 patients (2.4 %), and may have been caused by nucleotomy. However, only one was accompanied by aggravation of symptoms. Discitis was seen in 2 patients (0.8 %), both treated at two separate disc levels. About half the patients experienced increased low back pain, mean duration 9 days, after treatment, and 3 (1.2 %), of whom 2 also had nonorganic disorders, needed admission to hospital because of severe pain. Mild spasm and a sensation of instability were noted by 9.6 % and 25 % of the patients respectively. Injury to nerves, bowels, vessels or ureters or a dural leak never occurred. The study confirms earlier reports that the rate of serious complications is low.
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  • 71
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    Pediatric nephrology 11 (1997), S. 153-155 
    ISSN: 1432-198X
    Keywords: Key words: Acute renal failure ; Complications ; Multivariate analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Various factors were analyzed in 80 consecutive children under 16 years who had acute renal failure (ARF), for various prognostic factors. Overall mortality was 42.5%, with significantly higher levels seen in hemolytic uremic syndrome (68%, P 〈0.05) and associated with cardiac surgery (90.9%, P 〈0.01). Anuria (67.6% vs. 43.5%, P 〈0.05), need for dialysis (85.3% vs. 56.5%, P 〈0.05), neurological complications (50% vs. 6.3%, P 〈0.01), and respiratory complications (35.2% vs. 2.1%, P 〈0.01) were significantly higher in nonsurvivors than survivors. Multiple regression analysis showed the presence of neurological and respiratory complications to be poor prognostic factors.
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  • 72
    ISSN: 1432-198X
    Keywords: Key words: Bladder augmentation ; Renal failure ; Transplantation ; End-stage renal disease ; Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Ten consecutive patients with failure of urinary bladder augmentation (UBA) performed either prior to or after reaching end-stage renal disease (ESRD) were studied. Seven patients developed increased hydroureteronephrosis, infectious complications, and advanced to ESRD after UBA. The mean time to development of ESRD in patients who had UBA performed with moderate chronic renal failure (CRF) was 1.8 years. The UBAs in all seven patients were taken down prior to transplantation. Subsequently, five of these UBA-takedown patients have received kidney grafts and all have stable, good renal function. Three patients had their UBA performed after they reached ESRD, in preparation for renal transplantation. All three of these patients experienced recurrent urosepsis following transplantation, resulting in death in one patient and loss of graft in another. The third patient will undergo takedown of the UBA. This study suggests that UBA may possibly not be the best option for patients with moderate CRF and those awaiting transplantation.
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  • 73
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    Pediatric nephrology 11 (1997), S. 87-95 
    ISSN: 1432-198X
    Keywords: Key words: Angioaccess ; Arteriovenous fistula ; Graft ; Long-dwell catheters ; Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. In the light of many years’ experience in hemodialysis access surgery, the different methods of creating vascular access for dialysis treatment in the pediatric population are described. After presenting the various access types using autologous blood vessels and also heterologous grafts, their specific spectrum of complications is discussed in detail. Summarizing our experience it has to be emphasized that there is no specific angioaccess for children and adolescents, and that most vascular access procedures used in adults are also suitable for use in the young.
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  • 74
    ISSN: 1432-1912
    Keywords: Key words Neocortex ; Cholecystokinin ; Dynorphin ; Amino acids ; Microdialysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of sulphated cholecystokinin-8 (CCK-8S) on extracellular dynorphin B, aspartate, glutamate and GABA levels in the rat fronto-parietal cortex was investigated with in vivo microdialysis. The peptide was infused through the microdialysis probe trying to mimic local CCK-8S release. Basal levels of dynorphin B were around 20pM, aspartate 100nM, glutamate 600nM and GABA 30nM. CCK-8S (10μM) induced a ≈3-fold increase in extracellular dynorphin B, aspartate and glutamate levels, while GABA levels were only slightly increased. The effect of CCK-8S was restricted to the stimulated neocortex. Systemic pretreatment with the CCKB antagonist, L-365, 260, but not with the CCKA antagonist, L-364, 718, significantly antagonised the effect of CCK-8S on cortical dynorphin B and aspartate release. However, both CCKA and CCKB antagonists inhibited the increase in cortical glutamate levels. Thus, the present results indicate that cortical CCK release exerts a stimulatory modulation on cortical dynorphin B and aspartate release via the CCKB receptor subtype, and on glutamate release via both CCKA and CCKB receptor subtypes. Considering electrophysiological evidence that CCK increases neuronal firing rates in many brain regions, it may be suggested that CCK represents a stimulatory system modulating the function of the neocortex.
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  • 75
    ISSN: 1432-1912
    Keywords: Key words Morphine ; Nitric oxide ; Apomorphine ; Oxytocin ; Penile erection ; Yawning ; Paraventricular nucleus of the hypothalamus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possible involvement of nitric oxide in the prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning was investigated by measuring the concentration of NO2- and NO3- in the dialysate obtained with a vertical microdialysis probe implanted in the paraventricular nucleus of the hypothalamus of male rats. Either apomorphine (80 µg/kgs.c.) or oxytocin (30 ng i.c.v.) increased significantly basal NO2- and NO3- concentration in the paraventricular dialysate, penile erection and yawning. Morphine (1, 5 and 10mg/kg i.p.) prevented dose-dependently either apomorphine or oxytocin responses when given 15min before apomorphine or oxytocin. Prevention by morphine of apomorphine and oxytocin responses was abolished by naloxone (3mg/kg i.p.) given 15min before morphine. Morphine prevented apomorphine and oxytocin responses also when given in the lateral ventricles or directly in the paraventricular nucleus. In contrast, the selective agonist of the kappa opioid receptor subtype U-69,593 was found to be ineffective. The present results confirm previous findings showing that morphine acts through µ receptors in the paraventricular nucleus to prevent apomorphine and oxytocin-induced penile erection and yawning and suggest that this morphine effect is mediated by a decreased activity of nitric oxide in the paraventricular nucleus of the hypothalamus.
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  • 76
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    Naunyn-Schmiedeberg's archives of pharmacology 355 (1997), S. 689-698 
    ISSN: 1432-1912
    Keywords: Key words β-adrenoceptors ; β adrenoceptor antagonists ; Celiprolol ; Rat ; Blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Celiprolol is a β-adrenoceptor antagonist which has desirable ancillary properties since it is relatively cardioselective and can exert direct vasodilator and bronchodilator effects. Here agonist and antagonist effects of celiprolol at cardiac β1- and vascular β2-adrenoceptors were determined under in vivo conditions in the rat. All experiments were carried out in catecholamine-depleted, pentobarbital anesthetized and vagotomized rats, placed under artificial respiration. I.v. administrations were madevia the femoral vein. Blood pressure was measured from the cannulated right carotid artery and heart rate was recorded with a cardiotachometer. Celiprolol (10 µg/kg to 1 mg/kg i.v.) produced dose-related increases in heart rate and decreases in mean carotid artery blood pressure which were of longer duration than those mediated by standard agonists of β1-(isoprenaline) or β2-(salbutamol) adrenoceptors respectively. Although the maximal increase in heart rate by celiprolol (110±4 beats/min, n=7) was approximately half that of isoprenaline (198±1 beats/min, n=5), isoprenaline acted at doses 200-fold lower than celiprolol. Betaxolol (0.03-0.3 mg/kg i.v.), a β1-adrenoceptor antagonist, inhibited strongly and with similar potency the tachycardic effects of celiprolol (DR10 = 45 µg/kg i.v.) as well as isoprenaline (DR10 = 45 µg/kg i.v.). On the other hand, the hypotensive effects of celiprolol and salbutamol were antagonized markedly and with similar potency by ICI118,551, a relatively selective β2-adrenoceptor antagonist (DR10 = 15 and 25 µg/kg i.v. respectively). In rats pretreated with celiprolol (0.03 to 0.3 mg/kg i.v.), the heart rate dose-response curves to isoprenaline were shifted to the right of those determined in matched groups of vehicle-pretreated animals. In this respect, celiprolol was half as potent as betaxolol in blocking cardiac β1-adrenoceptors. Furthermore, celiprolol also antagonized the hypotensive effects of salbutamol, but, in this respect, celiprolol was 90-fold less potent than ICI 118,551. In conclusion, these results clearly indicate that celiprolol has the ability of stimulating and blocking not only cardiac β1- but also vascular β2-adrenoceptors. The effects on cardiac β1-adrenoceptors as well as the agonism of β2-adrenoceptors are produced by similar doses of celiprolol. These doses are notably lower than those necessary to block β2-adrenoceptors. Thus, this pharmacological profile, which has also been demonstrated in humans, indicates that celiprolol is a modulator of cardiac β1-adrenoceptors with vascular β2-adrenoceptor agonist properties.
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  • 77
    ISSN: 1432-1912
    Keywords: Key words γ2-MSH (γ2-melanocyte-stimulating ; hormone) ; Blood pressure ; Heart rate ; Prazosin ; Metoprolol ; SR 49059 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract γ2-Melanocyte-stimulating hormone (γ2-MSH) and related melanotropins have been shown to have various cardiovascular effects, including acute, short-lasting increases in blood pressure (MAP) and heart rate (HR). γ2-MSH, administered intravenously, dose-dependently increased MAP and HR with an ED50 of approximately 30 nmol/kg and a maximal effect on MAP of approximately 55 mm Hg and on HR of around 70 beats per minute. Intravenous (i.v.) pretreatment with the α1-adrenoceptor antagonist, prazosin, caused the dose-response curve for the effect of γ2-MSH on MAP to shift to the right with a decrease in slope, whereas it had no effect on the dose-response curve for the effect on HR. I.v. pretreatment with the β1-adrenoceptor antagonist, metoprolol, had no effect on the dose-response curve for the effect of γ2-MSH on MAP, but it caused the dose-response curve for the effect of the peptide on HR to shift to the right with a decrease in slope. Neither i.v. nor intracerebroventricular (i.c.v.) administration of the vasopressin V1A receptor antagonist, SR 49059 ((2S) 1-[(2R 3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide), had significant effects on the dose-response curves for the effects of the peptide on either MAP or HR. The doses of prazosin, metoprolol and SR 49059 were found to be effective in counteracting the effects of agonists for these receptors (phenylephrine, isoprenaline and [Arg8]vasopressin, respectively). Taken together, these results support the postulate that the effects of γ2-MSH are, at least partially, due to an increase in sympathetic outflow to the periphery (Gruber and Callahan (1989), Am J Physiol 257: R681-R694), and that this increase leads to increased activation of vascular α1-adrenoceptors and cardiac β1-adrenoceptors. If, as was suggested by these authors, γ2-MSH acts via activation of a central vasopressin system, it is via a vasopressin receptor subtype other than the vasopressin V1A receptor, since i.c.v. administration of a selective vasopressin V1A receptor antagonist failed to interfere with the pressor and cardioaccelerator effects of γ2-MSH.
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  • 78
    ISSN: 1432-1912
    Keywords: Key words N-Methyl-D-aspartate (NMDA) antagonists ; Locomotion ; Stereotypy ; Catalepsy ; Basal ganglia ; Dopamine antagonists ; Dopamine metabolism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of systemic administration of the non-competitive N-methyl-D-aspartate (NMDA) antagonists dextrorphan (10–40mg/kg, i.p.) and [±]-5-aminocarbonyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine (ADCI) (25–70mg/kg, i.p.) on basal ganglia-mediated behaviour and on forebrain dopamine metabolism were investigated in rats. Dextrorphan increased locomotor activity but did not induce stereotyped sniffing. ADCI failed to produce any significant motor stimulant and motor depressant actions. Both dextrorphan and ADCI dose-dependently antagonized catalepsy induced by the D-1 dopamine receptor antagonist SCH 23390 or the D-2 dopamine receptor antagonist haloperidol. Only the highest doses of dextrorphan and ADCI increased dopamine metabolism in the prefrontal cortex and/or in the nucleus accumbens, but not in the dorsal striatum. Our results show that dextrorphan and ADCI produce some of the behavioural effects (antagonism of experimentally induced catalepsy) and neurochemical actions (regionally selective stimulation of dopamine metabolism) that have previously been observed in the prototypical non-competitive NMDA antagonist, dizocilpine. The failure of ADCI to induce hyperlocomotion and stereotypy suggests that anticataleptic doses of ADCI may be devoid of the psychotomimetic actions commonly associated with non-competitive blockade of NMDA receptor function.
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  • 79
    ISSN: 1432-1912
    Keywords: Key words Daily rhythms ; Heart rate ; Temperature ; Locomotor activity ; Anaesthesia ; Ether ; Ketamine ; Rat ; Telemetry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to evaluate the effect of anaesthesia (ether or ketamine) on daily rhythms of temperature (T), heart rate (H) and locomotor activity (A) in unrestrained rats by using implanted radio-telemetry transmitters. T, H and A were measured every 10min, in Wistar male rats, and analysed using Cosinor. The mean±SEM days needed, after surgical implantation, to detect a daily rhythm in H, T and A were also assessed. Six rats were anaesthetized for about 50min either by ketamine or ether in a 3 by 3 cross-over design. Mesors, amplitudes and acrophases of T, H and A were calculated three days before (D-3; D-2; D-1), the day of anaesthesia (D0) as well as the three following days (D1; D2; D3). ANOVA was performed in order to detect, firstly a possible effect due to the order of application of anaesthesia, secondly a significant difference between ether or ketamine-induced anaesthesia and finally a modification of the mesors, amplitudes and acrophases of T, H and A, induced by each anaesthesia, for D0, D1, D2 and D3 when compared to D-1. Our results indicate: (1) Alterations of the acrophases, mesors and amplitudes, except for the amplitude of A, of the daily rhythms of T, H and A on D0 of ketamine anaesthesia while regarding ether anaesthesia only amplitude of T and H and acrophase of A were modified on D0. Some of these modifications were still observed on the days following anaesthesia. A significant difference between ether and ketamine-induced anaesthesia was also observed. (2) A non-detection of T, H and A daily rhythms after surgical implantation, which was not observed after injection of either ether or ketamine alone. Almost 10 days were needed to detect a significant daily rhythm for T, H and A. The authors suggest that, the general anaesthetic agent was responsible for a perturbation of the mesors, amplitudes and acrophases of the daily rhythms of H, T and A while the non-detection of these rhythms after implantation was more due to the surgical aggression.
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  • 80
    ISSN: 1432-1912
    Keywords: Key words Blood pressure ; GR127935 ; Hypotension ; 5Hydroxytryptamine ; 5ht7Receptor ; Rat ; Sumatriptan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been suggested that the late hypotensive response to serotonin (5hydroxytryptamine; 5HT) in vagosympathectomized rats is mediated by ‘5HT1like’ receptors since this effect is mimicked by 5carboxamidotryptamine (5CT), is not modified by cyproheptadine, ketanserin or MDL72222, but it is blocked by methysergide. The present study was set out to reanalyze this suggestion in terms of the classification schemes proposed in 1994 and 1996 by the NCIUPHAR subcommittee on the classification and nomenclature of 5HT receptors. I.v. bolus injections of 5CT (0.010.3μg·kg1), 5HT (130μg·kg1) and 5methoxytryptamine (5MeOT; 130μg·kg1) produced dosedependent hypotensive responses with a rank order of agonist potency: 5CT 〉〉 5HT ≥ 5methoxytryptamine with sumatriptan (301000μg·kg1) inactive. The depressor responses to 5HT and 5CT were not attenuated by i.v. GR127935 (3003000μg·kg1) or equivalent volumes of saline. In contrast, lisuride, methiothepin, mesulergine, metergoline and clozapine dose-dependently antagonized the responses to 5HT and 5CT; the rank order of apparent pA2 values against 5HT and 5CT, respectively, was: lisuride (7.7; 7.8) 〉 methiothepin (6.8; 7.0) ≥ mesulergine (6.4; 6.6) 〉 clozapine (5.7; 5.8); metergoline displayed variable potencies (5.6; 6.4). Except for lisuride, which also affected isoprenalineinduced hypotension, the antagonism by the other drugs was selective. Based upon the above rank order of agonist potency, the blockade by a series of drugs showing high affinity for the cloned 5ht7 receptor and the lack of blockade by GR127935, our results indicate that the 5HT receptor mediating hypotension in vagosympathectomized rats is operationally similar to other putative 5ht7 receptors mediating vascular and nonvascular responses (e.g. relaxation of the rabbit femoral vein, canine coronary and external carotid arteries and guineapig ileum as well as feline tachycardia).
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  • 81
    ISSN: 1432-1912
    Keywords: Key words Urinary bladder ; Hyperreflexia ; Tachykinin antagonists NK1 receptors ; Tachykinin antagonists ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigates the role of tachykinin NK1 and NK2 receptors in motor responses induced by the intravesical instillation of capsaicin in urethane-anaesthetized rats. SR 140,333 (1 µmol/kg, i.v.), a non-peptide NK1 receptor antagonist, abolished urinary bladder contractions induced by the selective NK1 receptor agonist [Sar9]SP-sulfone (0.1-100 nmol/kg, i.v.) without affecting those induced by the NK2 receptor agonist [ßAla8]NKA(4-10). MEN 11,420 (100 nmol/kg, i.v.), a cyclic peptide NK2 receptor antagonist, abolished bladder contractions induced by [ßAla8]NKA(4-10) (0.3-300 nmol/kg, i.v.) without modifying those induced by [Sar9]SP-sulfone. Intravesical instillation of capsaicin (6 nmol/0.6 ml/rat) produced a motor response consisting in a primary contraction followed by a series of high amplitude phasic contractions. The intravesical instillation of saline (0.6 ml/rat) produced a primary contraction of lower amplitude with respect to that induced by capsaicin and the total area under the curve was also lower in saline-instilled rats, however the number and the amplitude of phasic contractions was similar to that induced by capsaicin. MEN 11,420 (100 nmol/kg, i.v.) did not modify motor responses induced by the intravesical administration of saline. In contrast, in capsaicin-instilled rats, MEN 11,420 (100 nmol/kg, i.v.) reduced the primary contraction, the area under the curve and also the number of phasic contractions. SR 140,333 (1 µmol/kg, i.v.) reduced the primary contraction but not other parameters. The combination of SR 140,333 (1 µmol/kg, i.v.) and MEN 11,420 (100 nmol/kg, i.v.) produced an additive inhibitory effect on the primary contraction but not a further inhibition on other parameters with respect to that observed with MEN 11,420 alone. In hexamethonium (110 µmol/kg, i.v.)-pretreated animals the intravesical instillation of capsaicin produced a tonic contraction having greater amplitude and area than that induced by saline. MEN 11,420, but not SR 140,333, significantly reduced the bladder response to capsaicin in hexamethonium-pretreated rats. Again, the combined administration of MEN 11,420 and SR 140,333 did not produce further inhibitory effect in comparison to MEN 11,420 alone. It is concluded that the motor responses induced by the intravesical instillation of capsaicin are mediated by the activation of peripheral tachykinin NK2 receptors.
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  • 82
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    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 611-618 
    ISSN: 1432-1912
    Keywords: Key words Hippocampus ; EPSP ; IPSP ; GABA ; NMDA ; Epilepsy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous behavioural and electrophysiological studies have indicated that levetiracetam (ucb LO59) acts as an anticonvulsant drug in vivo. The purpose of the present study was to investigate the effects of levetiracetam on normal synaptic transmission and epileptiform activity in vitro. Intracellular recordings were obtained from the CA3 subfield of the rat hippocampal slice preparation. Levetiracetam in a concentration of 10 μM did not influence basic cell properties or normal synaptic transmission evoked by subthreshold and suprathreshold stimuli to the commissural pathway. However, it strongly inhibited the development of epileptiform bursting by the γ-aminobutyric acid (GABA)A-receptor antagonist bicuculline (1– 30 μM). Levetiracetam also decreased the size of bursts previously established by bicuculline. In experiments in which the glutamate-receptor agonist N-Methyl-D-Aspartate (NMDA) was used to generate spontaneous bursting, levetiracetam had no effect on the size of the bursts but decreased bursting frequency. The difference in effects of levetiracetam on bicuculline- and NMDA-induced bursting appeared to be dependent on the convulsant used, since in the presence of 10 μM bicuculline, levetiracetam decreased the size of NMDA-bursts to the same extent as the size of synaptically evoked bicuculline-bursts but had little effect on bursting frequency. The results show that under our experimental conditions, levetiracetam did not alter the components of normal synaptic transmission. However, levetiracetam at the concentrations studied inhibited epileptiform bursting induced by bicuculline and NMDA in vitro in a manner consistent with the profile of an antiepileptogenic drug.
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  • 83
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    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 297-302 
    ISSN: 1432-1912
    Keywords: Key words Lipid peroxidation ; Free radicals ; Oxidative stress ; In vitro ; In vivo ; Antioxidant ; Antiestrogen ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to investigate antioxidativity of the triphenylethylene antiestrogen toremifene. Toremifene and its structural analogues were studied for their ability to inhibit chain reactions of lipid peroxidation and to act as scavengers of free radicals in vitro, and the effects of toremifene were compared to those of the estrogens, tamoxifen and known antioxidants. Moreover, the in vivo antioxidativity of toremifene was tested in a long-term experiment with rats. The ability of toremifene to prevent lipid peroxidation was assayed in two different test systems. In the first assay (initiated with ascorbate/ADP-FeCl3, detection by the formation of TBA-reactive material) toremifene was found to act as an efficient membrane antioxidant with an IC50-value (18 μM) comparable to that of tamoxifen (26 μM) and α-tocopherol (43 μM). Toremifene derivatives 4-hydroxytoremifene (IC50 = 8 μM) and Fc 1159 (IC50 = 31 μM), as well as diethylstilbestrol (IC50 = 17 μM) were also active while estradiol showed only weak antioxidativity (IC50 = 300 μM) in this test system. In the other assay (peroxidation initiated with t-butylhydroperoxide, detection by luminol-enhanced chemiluminescence) toremifene prevented lipid peroxidation only at high concentrations (IC50 = 450 μM) but the metabolite 4-hydroxytoremifene (IC50 = 0.18 μM), estradiol (IC50 = 4.6 μM) and diethylstilbestrol (IC50 = 1.7 μM) showed potent antioxidant activity. The potency of 4-hydroxytoremifene even exeeded that of α-tocopherol (IC50 = 2.0 μM) and butylated hydroxyanisole (IC50 = 1.1 μM). Toremifene was found to have some superoxide anion but no peroxyl radical scavenging activity. Interestingly, diethylstilbestrol turned out to be a potent scavenger of peroxyl radicals. Treatment of female Sprague-Dawley rats with toremifene (12 or 48 mg/kg) was found to decrease serum levels of lipid peroxides. This was seen at various time points (2 days, 5 weeks, 6 and 12 months) during long-term administration of toremifene to rats, and results obtained with two different methods (diene conjugation, TBA-reactive material) gave similar results. The present study thus showed that (i) like steroidal estrogens and tamoxifen toremifene is a potent membrane antioxidant in vitro, (ii) the antioxidant action of toremifene is not due to scavenging of free radicals and, importantly, (iii) toremifene acts antioxidatively also in living organisms in vivo.
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  • 84
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    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 341-347 
    ISSN: 1432-1912
    Keywords: Key words Complex partial seizure ; Diphenylhydantoin ; Epileptic focus ; Limbic system ; Rat ; Threshold
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Phenytoin is a major antiepileptic drug for treatment of limbic seizures. The effect of phenytoin on the generation and spread of seizure activity was studied in a rat model of this type of seizures. Sprague-Dawley and Wistar rats were implanted with a stimulation and recording electrode in the basolateral amygdala. Naive Sprague-Dawley rats showed an increase in current intensity necessary for eliciting afterdischarges (afterdischarge threshold) of about 200% after administration of phenytoin (75 mg/kg i.p.), while seizure severity at threshold was increased compared to controls. Afterdischarge and seizure durations were significantly prolonged under phenytoin. This result suggests that phenytoin can exert a potent anticonvulsant effect on the generation of focal seizure activity, but it does not suppress or may even increase on-going afterdischarge activity once it occurs. Following amygdala kindling in Wistar rats, administration of phenytoin again resulted in an increase in the afterdischarge threshold. However, all rats still showed generalized seizures, and epileptic afterdischarges could be recorded in various limbic brain regions at threshold current. This result suggests that phenytoin can increase the threshold for generation of epileptic discharges in kindled rats, but is not able to prevent the development of generalized seizure activity and the spread of afterdischarges within the limbic system when focal activity is initiated. We conclude that phenytoin is able to suppress focal seizure activity in the amygdala kindling model of the rat. However, it does not prevent the spread of seizure activity originating in the limbic system. Therefore, a decrease in focal seizure susceptibility seems to be the primary target for phenytoin’s anticonvulsant action.
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  • 85
    ISSN: 1432-1912
    Keywords: Key words [3H]-Acetylcholine release ; Rat ; caudatoputamen ; Cholinergic interneurons ; Glycine ; receptors ; Serine ; Strychnine ; Ethanol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study acute effects of ethanol on [3H]-acetylcholine ([3H]-ACh) release induced by activation of strychnine-sensitive glycine receptors in superfused slices of rat caudatoputamen were investigated. The glycine-evoked [3H]-ACh release (lg EC50 = –4.10, CI95 = [–4.14, –4.05]) was inhibited by strychnine in a competitive manner (pA2 = 6.86, CI95 = [6.61, 7.08]). Release of [3H]-ACh could also be induced by L-serine. L-serine was less potent than glycine (lg EC50 = –2.61, CI95 = [–2.69, –2.52]). Both glycine and L-serine showed similar maximum effects (Emax(glycine) = 1.34, CI95 = [1.24, 1.45]; Emax(L-serine) = 1.19, CI95 = [1.09, 1.32]). Ethanol at concentrations of 2‰ (= 34 mM) and 4‰ (= 68 mM) inhibited glycine-evoked [3H]-ACh release in a manner like the competitive antagonist strychnine, however with lower potency. The pA2 of ethanol was 1.19, CI95 = [0.85, 1.41], at 2‰ [v/v] and 1.51, CI95 = [1.19, 1.78] at 4‰ ethanol. Similar to its action on glycine-evoked [3H]-ACh release, ethanol at 4‰ [v/v] also inhibited L-serine-evoked transmitter release in a competitive-like fashion (pA2 = 0.83, CI95 = [–0.15, 1.18]). We conclude, that strychnine-sensitive glycine receptors, mediating [3H]-ACh release in the rat caudatoputamen, might represent a new site of action of ethanol.
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  • 86
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    Der Radiologe 37 (1997), S. 197-204 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Lebertransplantation ; Komplikation ; Radiologische Diagnostik ; Key words Liver transplantation ; Complications ; Radiological diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Introduction: Orthotopic liver transplantation (OLT) has become an accepted treatment for end-stage liver disease. However, postoperative complications result in significant patient morbidity and mortality. Early detection and treatment of these complications is therefore of utmost importance. Materials and methods: We retrospectively reviewed the postoperative complications of the patients who underwent OLT at our institution. Duplex Doppler sonography and cholangiography were the primary imaging modalities in postoperative evaluation of the transplanted liver. Other important techniques were CT, MRI, and angiography, which may contribute to a reliable diagnosis of vascular or biliary complications. Results: Second to primary organ dysfunction, vascular complications are the most frequent cause of graft loss. Thrombosis of the hepatic artery is the most common and most serious vascular complication, with a reported incidence from 4 to 42 %. Bile duct sludge, leaks and strictures are frequent complications after liver transplantation, which can contribute to graft dysfunction. Biliary tract complications usually occur within the first 3 months and require interventional radiological or surgical therapy. Since liver transplant recipients undergo immunosuppressive therapy, they are at increased risk of developing late post-transplant malignancies, which are best depicted by US, CT or MRI. However, radiological diagnosis of lymphoproliferative disorder has to be confirmed by liver biopsy. Conclusion: Cholangiography and Duplex sonography are routinely used in the postoperative evaluation of patients with OLT. CT, MRI, and angiography are problem-solving tools in equivocal cases.
    Notes: Zusammenfassung Einleitung: Die orthotope Lebertransplantation hat sich zu einer etablierten Therapie bei Lebererkrankungen im Endstadium entwickelt. Der frühe Nachweis und die prompte Therapie eventueller Komplikationen sind für das Überleben des Patienten und des Organs entscheidend. Material und Methode: Es wurden im eigenen Krankengut die postoperativen Komplikationen nach OLT retrospektiv ausgewertet. Die Duplexsonographie und die Cholangiographie erwiesen sich als die primären Untersuchungsmethoden der Wahl zum Nachweis vaskulärer oder biliärer Komplikationen. CT, MRI und die Angiographie waren in Problemfällen wertvolle additive bildgebende Verfahren zur Diagnosesicherung. Ergebnisse: Nach der primären Organdysfunktion sind die vaskulären Komplikationen als häufigste Ursache für den Verlust des Spendeorgans anzuführen. Die Thrombose der A. hepatica ist die häufigste vaskuläre Komplikationen mit einer Inzidenz von 4–42 %. Galleleaks, -sludge und -strikturen sind häufige Komplikationen, die letztlich zu einer Dysfunktion des transplantierten Organs führen können. Biliäre Komplikationen treten gehäuft in den ersten 3 Monaten auf und erfordern eine interventionelle oder chirurgische Therapie. Da Patienten nach OLT einer immunsuppressiven Therapie unterliegen, sind sie einem erhöhten Risiko einen lymphoproliferativen Tumor zu entwickeln ausgesetzt. Diese Posttransplant-Tumore können mit US, CT und MRI ausgezeichnet abgegrenzt werden, erfordern jedoch eine Sicherung der Diagnose durch eine Feinnadelpunktion. Schlußfolgerung: Die postoperative Verlaufskontrolle und der Nachweis von Komplikationen nach OLT ist eine Domäne von Cholangiographie und Duplexsonographie. In Problemfällen kommen CT, MRI und Angiographie zum Einsatz.
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  • 87
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    Der Schmerz 11 (1997), S. 241-246 
    ISSN: 1432-2129
    Keywords: Schlüsselwörter Narkosekomplikationen ; Übelkeit ; Erbrechen ; Key words Anaesthesia ; Audit ; Complications ; Nausea ; Vomiting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Problem: Postoperative nausea and vomiting remains an important problem. Many risk factors have been identified; however, the importance of postoperative analgesic technique and patient expectation remain poorly defined. Methods:We prospectively collected data on postoperative nausea and vomiting (PONV) in four groups of randomly selected patients (n=50 per group) who received either simple analgesics, nurse-administered intravenous morphine (NAA), patient-controlled analgesia (PCA) with morphine or epidural analgesia with bupivacaine and fentanyl. Patients were questioned regarding any past history of PONV or motion sickness, their preoperative expectation of suffering PONV and satisfaction with their antiemetic therapy. Results: The incidence of nausea was higher in both morphine groups P〈0.05), women (P〈0.05), those less than the median age of their group (P〈0.05) and those with a past history of PONV (P〈0.05) or motion sickness (P〈0.05). Most patients did not expect to experience PONV (19.3%). The incidence of nausea was higher in those expecting to experience PONV than in those not expecting to suffer PONV (P〈0.01). Of those who received postoperative antiemetic treatment, 23.6% were dissatisfied or very dissatisfied with their therapy. Few patients received a prophylactic antiemetic drug (15%). Conclusions: Study results show that patient expectation is a potent predictor of postoperative nausea, a risk factor hitherto ignored in the anaesthetic literature, and that, in the provision of analgesia following major surgery, epidural analgesia is associated with less PONV than intravenous morphine.
    Notes: Zusammenfassung Übelkeit und Erbrechen (PONV) sind nach wie vor ein Problem der postoperativen Phase. Viele Risikofaktoren sind bekannt, jedoch sind die Bedeutung der unterschiedlichen postoperativen analgetischen Regimes und die Erwartungshaltung der Patienten wenig untermauert. Patienten: Prospektiv wurden 4 randomisierte Patientengruppen untersucht (n=50/Gruppe), die postoperativ einfache Analgetika (Gruppe 1), durch eine Krankenschwester verabreichte i.v. Morphingaben (NAA; Gruppe 2), eine patientenkontrollierte Analgesie (PCA; Gruppe 3) und eine Epiduralanalgesie mit Bupivacain und Fentanyl (Gruppe 4) erhielten. Bei den Patienten wurde ermittelt, ob sie bei Voroperationen an Übelkeit und Erbrechen litten. Zusätzlich wurde die Erwartungshaltung der Patienten gegenüber PONV und deren Zufriedenheit mit der antiemetischen Therapie untersucht. Ergebnisse: Die Inzidenz von PONV war bei beiden Morphingruppen, bei Frauen, bei Patienten, die älter waren als der Median der Gruppe, und bei solchen Patienten, die in ihrer Vorgeschichte an PONV und Seekrankheit litten, höher. Die meisten Patienten hatten nicht erwartet, postoperativ Übelkeit und Erbrechen zu erleiden (19,3%). Bei Patienten, die präoperativ PONV erwarteten, war die Inzidenz höher als bei Patienten, die über diese Erwartungshaltung nicht berichteten (p〈0,01). Ein Viertel der Patienten (23,6%) war mit der postoperativen antiemetischen Behandlung unzufrieden oder sogar sehr unzufrieden. Eine präoperative Prophylaxe erhielten 15% der Patienten. Schlußfolgerung: Die Studie zeigt, daß die Erwartungshaltung der Patienten, an postoperativer Übelkeit und postoperativem Erbrechen zu leiden, ein in der Literatur unterschätzer Vorhersagefaktor ist. Bei der postoperativen Schmerztherapie bietet die Epiduralanalgesie im Vergleich zur i.v. Morphingabe deutliche Vorteile.
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    Psychopharmacology 129 (1997), S. 249-256 
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Acute tolerance ; Ibogaine ; Dopamine ; Microdialysis ; In vivo ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is increasing evidence that the rewarding effect of nicotine is mediated by the mesolimbic dopamine system. The first objective of this study was to examine the dopamine response to repeated IV infusions of nicotine. Using in vivo microdialysis in awake and freely moving male Sprague-Dawley rats, we demonstrated that IV nicotine infusions (0.16 mg/kg or 0.32 mg/kg per infusion) produced increases in extracellular dopamine levels that were dose- and infusion order-dependent. Acute tolerance was evidenced by the smaller dopamine response produced by a second infusion of nicotine, administered 1 h after the first one. Tolerance was reversible, since the dopamine response to a second infusion of nicotine was unchanged when the interval between the infusions was increased to 3 h. Ibogaine, an alkaloid found in Tabernanthe iboga, is claimed to decrease smoking and to have an anti-nicotinic action. The second objective of this study was to establish whether this claim has any neurochemical basis. Pretreatment with ibogaine (40 mg/kg, IP) 19 h prior to the first nicotine infusion (0.32 mg/kg per infusion) significantly attenuated the increase in extracellular dopamine levels induced by the nicotine infusions, suggesting that ibogaine may decrease the rewarding effect of nicotine.
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  • 89
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Drug discrimination ; Dopamine (DA) ; Human ; Rat ; Reuptake inhibitor ; Reinforcing effects ; Self-administration ; Serotonin (5-HT) ; 5-HT1A ; 5-HT2 ; 5-HT3 ; Subjective effects ; Stimulus effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose of the present manuscript is to review the current status of the role of serotonin (5-hydroxytryptamine; 5-HT) systems in the stimulus and reinforcing properties of cocaine in non-humans and the subjective effects of cocaine in humans. Review of the current literature suggests that general enhancement (via precursor administration) or depletion of brain 5-HT content (via neurotoxin administration or tryptophan depletion) impact the reinforcing effects of cocaine in non-humans and its subjective effects in humans. Selective 5-HT reuptake inhibitors (SSRIs) enhance the discriminability of cocaine and decrease cocaine self-administration in animals, although data to the contrary also exist. Studies in humans suggest that SSRIs attenuate the subjective effects of cocaine in humans. Although few drugs with selectivity for 5-HT2 receptors have been studied systematically, a 5-HT2 agonist and several antagonists show some efficacy in enhancing and reducing, respectively, the reinforcing effects of cocaine in non-humans. Limited data from humans suggest that a 5-HT2 antagonist may also decrease the subjective effects of cocaine; thus, 5-HT2 compounds deserve further attention. The majority of studies evaluating the 5-HT3 antagonists have reported negative results across all paradigms. In summary, while the functional significance of 5-HT receptors has not been fully elucidated, these data suggest that changes in serotonergic activity can modulate the effects of cocaine in both animals and humans under a variety of experimental conditions. One commonality among the studies with positive findings is that cocaine effects are only partially modified by 5-HT agents regardless of the direction of change.
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  • 90
    ISSN: 1432-2072
    Keywords: Key words 5-Hydroxytryptamine ; 5 ; 7-Dihydroxytryptamine ; Operant behaviour ; Time discrimination ; Memory for duration ; Interval bisection procedure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways on memory for duration, using a delayed interval bisection task. Rats that had received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei, and sham-lesioned control rats, were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus, and lever B following an 8-s presentation of the same stimulus. Following stimulus offset a response on a panel placed midway between the two levers was required in order to initiate lever presentation; a single response on either lever resulted in withdrawal of both levers and, in the case of a ‘correct’ response, reinforcer delivery. When 〉 90% correct choices had been attained, an 8-s (phase I) or a 12-s (phase II) delay was interposed between stimulus offset and lever presentation in 50% of the trials, and probe trials (10% of both non-delay and delay trials) were introduced in which the light was presented for intermediate durations. Logistic functions were derived relating percent choice of lever B to stimulus duration. In both groups, the imposition of post-stimulus delays displaced the bisection point (duration yielding 50% choice of lever B) towards longer durations; this effect was significantly greater in the lesioned group than in the control group. Imposition of post-stimulus delays resulted in increases in the Weber fraction, which did not differ significantly between the two groups. The levels of 5HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered.
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  • 91
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Reinforcement ; Intravenous self-administration ; Strain differences ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Nicotine has been shown to maintain intravenous self-administration behaviour in humans and laboratory animals. However, factors critical in the initiation of nicotine self administration are not well defined. In particular genetic differences and effects of pre-exposure to nicotine have not been examined. Male Sprague-Dawley or Long-Evans rats were surgically prepared with indwelling jugular catheters and 3 days later received chronic injections of nicotine (0.4 mg/kg SC) or vehicle (saline, 1 ml/kg) for 7 days in their home cage. The next day, 2-h daily test sessions were initiated, during which rats were given the opportunity to nose-poke for nicotine infusions (0.015, 0.03 or 0.06 mg/kg per infusion) under a one-response fixed-ratio (FR-1) schedule of reinforcement with a 20-s time out after each infusion. One hole was defined as active while pokes in the other hole were recorded but had no scheduled consequence. The response requirement was increased progressively to five (FR-5) over successive sessions. Both saline- and nicotine-pretreated Sprague-Dawley rats showed a preference for the active hole, while only the saline-pretreated Long-Evans rats acquired the self-administration as defined by significant differences between responding in the active versus the inactive holes. The Fisher (F344) and Lewis inbred strains also failed to acquire self-administration of nicotine under these conditions. With Sprague-Dawley and Long-Evans rats that acquired the self-administration, and showed stable levels of maintained responding for nicotine, substituting saline for the nicotine or pretreating with mecamylamine (2.0 mg/kg SC) extinguished the behaviour. When dose per infusion was varied, an inverted U-shaped dose-response curve was obtained. These results support previous reports that nicotine can serve as a reinforcer in rodents and demonstrate that environmental factors such as prior nicotine exposure or genetic factors such as rat strain can affect acquisition of nicotine self-administration.
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  • 92
    ISSN: 1432-2072
    Keywords: Key words Dopamine ; Benzodiazepine ; Neuroleptic ; Amphetamine ; Conditioned reinforcement ; Anxiety ; Punishment ; Conditioned stimulus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In a test of conditioned punishment, saline-treated controls showed a moderate bias in responding away from a lever producing a response-contingent auditory conditioned stimulus (CS) that had been paired with mild footshock during training and towards a lever producing a neutral auditory CS. Systemic treatment with the indirect dopamine (DA) agonist amphetamine (0.25–1.0 mg/kg) produced a dose-dependent increase in the punishing effect of the aversive CS, whilst responding on the neutral CS lever was unchanged. Treatment with the dopamine-receptor antagonist α-flupenthixol (0.125, 0.25 mg/kg) decreased the efficacy of the punishing CS, but again left responding on the neutral lever unchanged. The benzodiazepine midazolam (0.1, 0.3 mg/kg) had a similar effect to α-flupenthixol, but treated animals showed a preference for the aversive CS. Parallel results were observed with amphetamine (0.25 mg/kg) and α-flupenthixol (0.125, 0.25 mg/kg) in a matched test of positive conditioned reinforcement, with amphetamine enhancing, and α-flupenthixol reducing, the efficacy of the CS paired with food. Midazolam treatment (0.1–1.0 mg/kg) had no effect on the reinforcing impact of an appetitive CS. Thus dopaminergic agents modulate the behavioural impact of both appetitively and aversively motivated conditioned stimuli on instrumental performance, whilst the benzodiazepine midazolam has a selective impact on aversively-motivated stimuli that is qualitatively distinct from that of the dopaminergic antagonist α-flupenthixol.
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  • 93
    ISSN: 1432-2072
    Keywords: Key words NNC 19-1228 ; NNC 22-0031 ; Dopamine ; Neuroleptic ; Behavioral models ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract NNC 19-1228 [1-(3(6-benzothiazolylcarbamoyloxy)propyl)-4-(6-flouro-1,2-benzisoxazol-3-yl)piperidine] and NNC 22-0031 [4-(6-flouro-1,2-benzisoxazol-3-yl)-1-(3-(3,4-methylenedioxyphenylcarbamoyloxy)propyl)piperidine] are newly developed compounds with an in vitro pharmacologic profile similar to that of clozapine, i.e., mixed dopamine (DA), 5-hydroxytryptamine (5-HT)2 and α1-adrenergic antagonist action. In pharmacological experiments in mice, the compounds inhibited DA D2 receptor binding in vivo at doses that produced only moderate antagonism of methylphenidate (MPD)-induced stereotyped gnawing. However, the compounds were markedly more potent in blocking MPD-induced motility, a model which showed a high degree of sensitivity to α1-adrenergic antagonism, but not 5-HT2 antagonism. In rats, the NNC-compounds blocked conditioned avoidance responding and attenuated the discriminative stimulus effects of amphetamine, but failed to induce catalepsy. These results are discussed in terms of adrenergic, serotonergic and dopaminergic interactions which suggest that the NNC compounds may act as DA antagonists with mesolimbic selectivity, and thus may have efficacy as antipsychotics without coincident extrapyramidal side effects.
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  • 94
    ISSN: 1432-2072
    Keywords: Key words Sertraline ; Imipramine ; β-receptor ; 5-HT2 receptor ; 5-HT1A receptor ; Adenylate cyclase ; Water wheel test ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Effects of chronic treatment with selective 5-HT reuptake inhibitors (SSRIs) on the monoaminergic functions have not been much investigated in compared with tricyclic antidepressants. Therefore, we compared the effects of 3-week treatment with sertraline, a potent SSRI, to those of imipramine (10 mg/kg, IP, twice a day), on monoamine receptors and adenylate cyclase (AC) activity in rat brain. Two-week treatment with both sertraline and imipramine reduced immobility in the water wheel test to the comparable extent. Sertraline treatment did not affect Kd and Bmax of [3H]CGP12177 and [3H]ketanserin bindings or cAMP accumulation by norepinephrine, isoproterenol, 5’-guanylylimidodiphosphate [Gpp(NH)p] and forskolin in the cortical membrane compared with vehicle-treated rats. On the other hand, imipramine treatment decreased Bmax of both bindings and norepinephrine- or isoproterenol-stimulated cAMP accumulation. Treatment with either antidepressant induced no apparent changes in [3H]8-OH-DPAT [2-(N, N-dipropylamino)-8-hydroxy-1,2,3,4-tetrahydronaphthalene] binding in the hippocampal membrane. These results suggested that chronic treatment of sertraline induced little effect on monoamine receptors and AC activity in the brain and that the alteration of these functions may not be primarily involved in antidepressive effects of antidepressants, at least of SSRIs.
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  • 95
    ISSN: 1432-2072
    Keywords: Key words Buprenorphine ; Drug abuse ; Place preference ; Taste aversion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Buprenorphine, a mixed agonist-antagonist opioid with considerable analgesic activity, is currently indicated as a therapeutic agent with low abuse potential. Nevertheless, buprenorphine abuse has been recently reported from some countries. Thus the present experiments were performed to characterize further the motivational properties of buprenorphine in rats. Rewarding and aversive effects were assessed by place preference and taste aversion conditioning, respectively. It was found that buprenorphine (0.025, 0.050, 0.100 mg/kg SC) causes a significant increase in the amount of time spent on the conditioned side, but no significant decrease in saccharin consumption. Therefore buprenorphine data are not consistent with the general finding that psychoactive drugs cause rewarding and aversive effects within a similar dose range.
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  • 96
    ISSN: 1432-2072
    Keywords: Key words Zopiclone ; Hypnotic ; Intermediate stage ; Paradoxical sleep ; Theta rhythm ; Spindle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study examined the influence of zopiclone, a third generation hypnotic, on the transition from slow wave sleep to paradoxical sleep (PS) which is increased at the expense of PS by barbiturates and benzodiazepines. The compound decreased sleep latency and increased the latency of the intermediate stage (IS) and PS at 2.5, 5 and 7.5 mg/kg IP. The amount of the IS was decreased because of the decrease in phase number up to 6 h at all doses. PS amount was decreased during 2 h at 2.5 mg/kg and during 4 h at 5 and 7.5 mg/kg also because of the decrease in phase number. The IS never substituted for PS. The IS spindle characteristics were not modified and the theta rhythm frequency slightly decreased at 5 mg/kg (IS) and 7.5 mg/kg (PS).
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  • 97
    ISSN: 1432-2072
    Keywords: Key words Acoustic startle response ; Anterodorsal striatum ; Dopamine ; Glycine ; NMDA ; Nucleus accumbens ; Prepulse inhibition ; AP-5 ; 7-Chlorokynurenate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study examined the role of the strychnine-insensitive glycine binding site of the NMDA receptor in prepulse inhibition (PPI) of the acoustic startle response (ASR) in rats. PPI is an operational measure of gating processes which normally lead to a diminished ASR when a startling stimulus is preceded by a weak prepulse. PPI is impaired in schizophrenics and, therefore, experimentally induced PPI deficits in rats can be regarded as a model for gating deficits in schizophrenia. Local administration of 7-chlorokynurenate (7-CLKYN), an antagonist of the strychnine-insensitive glycine site of the NMDA receptor, into the nucleus accumbens reduced PPI. This sensorimotor gating deficit was antagonized by systemic pretreatment of the rats with the glycine site agonist D-cycloserine, indicating that the effect of 7-CLKYN was due to a blockade of the NMDA receptor associated glycine binding site. A similar deficit in PPI was observed after intra-accumbal administration of the competitive NMDA receptor antagonist AP-5. PPI was normal after injecting these drugs into the anterodorsal striatum. The hypothesis that the PPI deficit is accompanied by a change in dopamine release was tested by a neurochemical analysis of the effects of local injection of 7-CLKYN. Microdialysis data showed no increase of accumbal and striatal dopamine release after blockade of the glycine site with 7-CLKYN. Our data demonstrate that the glycine/NMDA receptor in the nucleus accumbens plays a important role in sensorimotor information processing that depends not on a hyperactive dopamine system.
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  • 98
    ISSN: 1432-2072
    Keywords: Key words Amisulpride ; Antipsychotics ; Apomorphine ; Clozapine ; Dopamine ; Haloperidol ; Prazosin ; Prepulse inhibition ; Rat ; Raclopride ; Remoxipride ; Risperidone ; Schizophrenia ; Startle reflex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prepulse inhibition (PPI) of the startle reflex – whereby presentation of a weak prepulse preceding a startling pulse diminishes the amplitude of the startle reflex – is disrupted by dopamine (DA) agonists; this disruption can be reversed by antipsychotics. There are also some indications in the literature that a few antipsychotics (most notably clozapine and haloperidol) may, on their own, have effects opposite to those of DA agonists, i.e. may enhance PPI. In order to explore these antipsychotic-induced potentiations of PPI more thoroughly, we assessed, in Sprague-Dawley rats, the effects of IP administration of various clinically effective antipsychotics in a PPI procedure with levels of PPI (ranging from 5 to about 40%) low enough to facilitate detection of PPI-potentiating effects of drugs. Both clozapine (5–20 mg/kg) and haloperidol (0.25–1 mg/kg) robustly and dose-dependently potentiated PPI. A similar effect was not seen with risperidone (0.1–1 mg/kg) or with the three substituted benzamides amisulpride (10–60 mg/kg), raclopride (0.1–3 mg/kg) and remoxipride (1–10 mg/kg). As risperidone is known to have prominent 5-HT2 antagonistic activity, these results do not indicate a role for 5-HT2 receptors in the clozapine and haloperidol PPI-enhancing effects. The absence of effects with the benzamides and with risperidone, at doses with known anti-dopaminergic activity, suggests that DA antagonist activity is not involved. The demonstration that prazosin (3–20 mg/kg), a non-antipsychotic with α1 adrenoceptor antagonistic properties, dose-dependently potentiated PPI indicates that α1 receptors might mediate the clozapine and haloperidol PPI-enhancing activity. Additionally, the finding that diazepam (1–10 mg/kg) did not enhance, but on the contrary reduced PPI, argues against a sedation- or general depressant-mediated effect of clozapine, haloperidol and prazosin. The negative results with four clinically active antipsychotics (risperidone and the benzamides), and the positive result with the non-antipsychotic prazosin, indicate that this PPI-enhancing procedure has poor predictive validity as a screening tool for potential antipsychotics.
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  • 99
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 133 (1997), S. 51-54 
    ISSN: 1432-2072
    Keywords: Key words Conditioned taste aversion ; Lithium ; Serotonin ; 5-HT1A receptor ; 8-OH-DPAT ; Pindolol ; p-MPPI ; PCPA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Experiments were carried out using rats to investigate whether 5-HT1A neural mechanisms are involved in lithium-induced conditioned taste aversion (CTA). We found that the 5-HT1A antagonists p-MPPI and pindolol caused CTA similar to that produced by LiCl. The 5-HT1A agonist 8-OH-DPAT counteracted lithium-induced CTA. Pindolol dose-dependently abolished effects of 8-OH-DPAT on LiCl-induced CTA. These findings support the notion that lithium has antagonistic actions on 5-HT1A receptors. Inhibition of 5-HT synthesis by PCPA failed, however, to prevent lithium-induced CTA. Evidently, mechanisms other than those governed solely by 5-HT are also involved in lithium-induced CTA.
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  • 100
    ISSN: 1432-2013
    Keywords: Key words Mast cells ; Endothelial cells ; Cell adhesion molecules ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Mast cell (MC)-mediated induction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and of E-selectin was studied in cultures of rat heart endothelial cells (EC) and human umbilical vein EC (HUVEC) respectively. MC induced VCAM-1 and E-selectin, but hardly any ICAM-1 in EC. Induction was not dependent on MC degranulation, but seemed to be provoked by constitutively released substances, other than histamine, from MC. Co-incubation of MC and EC, allowing for direct contact between the two cell types, was more potent in induction than MC co-incubated separately from EC using a permeable membrane. MC were less potent in induction than exogenous added cytokines or LPS. Induction of cell adhesion molecules in rat heart EC was MC-specific, since EC incubations with either rat cardiomyocytes or heart fibroblasts had no effect. The data show that rat MC, independent of degranulation, secrete mediators relevant for the induction of a specific set of EC adhesion molecules in vitro. This suggests a (supportive) role for MC in cell-adhesion molecule induction in the endothelium in settings of early or mild inflammation. The results are discussed in the context of inflammatory processes in the heart in vivo.
    Type of Medium: Electronic Resource
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