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  • 2000-2004  (150)
  • Children  (91)
  • Cell & Developmental Biology
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  • 1
    ISSN: 1432-2277
    Keywords: Key words Implantation model ; Aortic valves ; Valve dysfunction ; Rejection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Structural failure of heart valve allografts may be related to technical factors or immunological reactions. To circumvent nonimmunological factors a new rat implantation model was developed to study whether alloreactivity results in histopathological changes and valve dysfunction. Syngeneic (WAG-WAG, DA-DA) and allogeneic (WAG-BN, WAG-DA) transplantation was carried out using this new technique, and the function of explanted valves was assessed 21 days later by retrograde comptence testing. Additionally, grafts were examined using standard histological and immunohistochemical techniques. There was no leakage during retrograde injection in nine of tem syngeneic and two of ten allogeneic grafts. Microscopically, syngeneic valves appeared normal without fibrosis or intimal thickening, although CD8+ lymphocytes and macrophages were found in necrotic myocardial rim and adventitia. In contrast, allogeneic valves were deformed and noncellular, with extensive infiltration of CD4+, CD8+ and CD68+ cells in adventitia and media. Absence of fibrosis and intimal thickening in syngeneic transplanted valves indicated circumvention of nonimmunological factors. Allogeneic valve transplantation induces cellular infiltration in the graft with subsequent graft failure.
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  • 2
    ISSN: 1432-2277
    Keywords: Key words Hypoxia-reoxygenation ; JNK1/SAPK1 ; Rat ; Hepatocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Organ injury after ischemia and reperfusion (I/R) remains one of the most important limiting factors in liver surgery and transplantation. Oxygen-free radical (OFR) generation is considered a major cause of this damage. JNK1/SAPK1, a member of MAPK family, regulates cell adaptation to stressful conditions. The aim of this study was to determine if hypoxia-reoxygenation (H/R) can activate JNK1/SAPK1 and if OFR are involved in this activation. Primary cultured rat hepatocytes isolated from other liver cells and blood flow were submitted to warm and cold H/R phases mimicking surgical and transplant conditions. JNK1/SAPK1 was activated by both warm and cold H/R. Deferoxamine (1 mM), di-phenyleneiodonium (50 μM) and N-acetylcysteine (10 mM) significantly inhibited this kinase activation.
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  • 3
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; Posttransplant lymphoproliferative disease ; Epstein-Barr virus ; Humans ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Epstein-Barr virus (EBV) infection can induce uncontrolled lymphocyte B proliferation in immunosuppressed transplant patients. Monitoring circulating EBV-infected lymphocytes can help in identifying patients at risk of posttransplant lymphoproliferative disease (PTLD). Circulating EBV genome levels were determined in 54 liver transplant pediatric recipients. Ten patients had more than 500 EBV genome/105 peripheral blood lymphocytes (PBL) and exhibited clinical manifestations of EBV infection; three developed PTLD. To treat EBV infection, the level of immunosuppression was reduced and acute rejection developed in 4 patients. Three were treated with steroid and one had to be switched from cyclosporine to tacrolimus. Treatment of acute rejection was associated with increases in circulating EBV genome. None of the patients with less than 500 EBV genome/105 PBL developed PTLD or EBV infection. Monitoring of EBV DNA is useful in the management of EBV infection and PTLD following pediatric liver transplantation. EBV infection should be treated in ways which do not expose patients to the risk of rejection.
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  • 4
    ISSN: 1432-2277
    Keywords: Key words Small bowel transplantation ; Split tolerance ; FK 506 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Functional long-term allograft survival after experimental small bowel transplantation (SBT) is limited by chronic rejection. Initial application of high-dose FK 506 has been shown to induce stable long-term graft function. In order to examine whether this long-term function is associated with donor-specific tolerance, we analyzed the functional status of recipient T cells in vivo and in vitro. One-step orthotopic SBT was performed in the allogeneic Brown Norway (BN)-to-Lewis rat strain combination. FK 506 was given daily at a dose of 2 mg/kg from days 0–5 in the rejection model and from days 0–9 in the long-term functional model. Mean survival time in the rejection model was 98 ± 2.8 days. Histological examination of these small bowel allografts disclosed signs of chronic rejection. In contrast, all animals of the long-term functional model survived long term ( 〉 250 days) without clinical signs of chronic rejection. The latter model, furthermore, produced evidence of donor-specific tolerance. Whereas heterotopic Dark Agouti (DA) hearts were rejected regularly within 7 days, BN hearts survived indefinitely ( 〉 70 days). In vitro, mixed leukocyte reactivity of CD4 + T cells was similarly strong against donor (BN) antigens as against third-party (DA) antigens. The split tolerance revealed by our in vivo and in vitro results enabled acceptance of both the small bowel allograft without signs of chronic rejection and of donor-specific heart allografts.
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  • 5
    ISSN: 1432-2307
    Keywords: Key words T-type calcium channel blockade ; Mibefradil ; Myocardial infarction ; Cardiac remodeling ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Fibrillar collagen accumulates within the interstitium and around coronary arteries following cardiac failure and is responsible for abnormal myocardial stiffness and reduced coronary performance associated with impaired cardiac function. The aim of the study was to determine the effects of long-term treatment with the T-type calcium channel antagonist mibefradil on myocardial remodeling and cardiac function after chronic myocardial infarction (MI). MI was induced by permanent ligation of the left coronary artery in male Wistar rats. Animals were assigned to sham-operated, placebo-treated or mibefradil-treated (10 mg/kg per day p.o.) MI groups. Treatment with mibefradil was started either 7 days before, 24 h after, or 7 days after ligation and continued for 6 weeks after MI. At this time point, mean arterial blood pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP) and cardiac contractility (dP/dtmax) were measured in conscious rats. Morphometric parameters were determined in picrosirius red-stained hearts: total heart weight (THW), interstitial and perivascular collagen volume fraction (ICVF, PCVF), myocardial infarct size (IS), vascular perimeter (VP), inner vascular diameter (IVD) and media thickness (MT). Six weeks after MI, MAP and dP/dtmax were decreased, and LVEDP was increased in placebo-treated animals. In mibefradil-treated animals whose treatment started 7 days before or 24 h after MI, MAP and dP/dtmax were higher, and LVEDP was lower than in placebo-treated controls. THW, ICVF, PCVF and MT were higher in placebo-treated animals. Mibefradil treatment resulted in higher ICVF and IS, higher VP and IVD (when started 7 days before MI) and lower PCVF and MT (when started 7 days before or 24 h after MI) than were observed in placebo-treated controls. Chronic treatment with mibefradil reduced interstitial and perivascular fibrosis and improved cardiac function in MI-induced heart failure in rats. Cardiac remodeling was best prevented when treatment was begun before the ischemic event.
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  • 6
    ISSN: 1432-2307
    Keywords: Keywords 7 ; 12-dimethylbenz(a)anthracene ; Rat ; Submandibular gland ; Adenocarcinoma Myoepithelial cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In an attempt to induce adenocarcinoma containing myoepithelial cells (MECs) in the rat submandibular gland, we injected 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in acetone into the glands of rat pups at the age of 10 days. In both male and female pups, the glands, including their developing terminal secretory units, contained far greater numbers of cells positive for proliferating cell nuclear antigen (PCNA) than did adult glands. A single administration of 1% DMBA (0.05 ml/130 g b.w.) did not produce adenocarcinoma, but did induce occasional sarcomas, such as rhabdomyosarcoma and fibrosarcoma, in 2 months. Most glands regenerated with minimal scar formation. Microscopically, these glands were atypical in that they contained increased numbers of PCNA-positive cells, underdeveloped granular ducts, and striated ducts surrounded by MECs positive for alpha smooth muscle actin (αSMA). Though these features were also observed in the regenerated glands after acetone injection, the number of PCNA-positive cells was relatively high in the glands of DMBA-treated females, especially in the terminal secretory unit. The second DMBA injection at 10 weeks of age produced adenocarcinoma made up of αSMA-positive MECs and keratin 19-positive duct cells. Such MEC-associated adenocarcinoma was induced in the glands of more than half the female but not the male animals. Replacement of either of the double DMBA treatments with acetone, or DMBA treatment, single or double, of adult glands did not produce adenocarcinoma, but did produce sarcoma and squamous cell carcinoma. These results suggest that (1) at least two genetic mutations are necessary for induction of adenocarcinoma with MECs in the rat submandibular gland, (2) the mutation is efficiently introduced to pup glands whose terminal secretory units exhibit extreme proliferative activity, and (3) the second mutation is difficult to introduce in male glands, whose proliferative activity is relatively low, and/or transformed cells need some female hormone after the mutation to propagate.
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  • 7
    ISSN: 1432-2161
    Keywords: Key words Bone mineral density ; Dual energy X-ray absorptiometry ; Children ; Rickets ; X-linked hypophosphatemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To evaluate the bone mineral status of children being treated for X-linked hypophosphatemia, including potential differences between cortical bone in the radial diaphysis and combined cortical and trabecular bone in the lumbar spine. Design and patients. Forty-four bone mineral evaluations were performed in 11 children and adolescents with X-linked hypophosphatemia. Bone mineral density (BMD) of the lumbar spine and the radial diaphysis were measured by dual X-ray absorptiometry (DXA), second metacarpal cortical thickness was measured on hand radiographs, and these results were expressed as Z-scores (standard deviations from the mean). Results. For the 11 initial examinations, Z-scores (mean±SD) were: radial BMD, –2.73±1.15, lumbar BMD, +1.28±1.53; and cortical thickness, –2.21±0.95. Lumbar BMD Z-scores were significantly greater than those for radial BMD and cortical thickness. On follow-up examinations there was a mild increase in radial BMD and decrease in lumbar BMD. Although these changes were statistically significant, they were quite small and the discordance between radial and lumbar BMD was not corrected. Conclusions. Children and adolescents who are being treated for X-linked hypophosphatemia manifest a bone mineral disorder characterized by decreased BMD in the appendicular skeleton and increased BMD in the lumbar spine. Although current therapy is successful in its anti-rachitic effects, it does not correct this bone mineral disorder and additional therapeutic trials should be considered.
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  • 8
    ISSN: 1432-2129
    Keywords: Schlüsselwörter ; Kopfschmerz ; Kinder ; Akuttherapie ; Flupirtin ; Paracetamol ; Keywords ; Children ; Acute treatment ; Tension-type headache ; Flupirtine ; Paracetamol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background: About 10% of all schoolchil- dren are suffering from migraine and 50% from tension-type headache. Headache of acute onset usually will be treated with analgesic substances like paracetamol, acetylsalicylic acid or ibuprofen, the first one being the reference drug for tension-type headache in childhood. In case of lacking improvement or side-effects there is demand for an alternative safe substance for the acute analgesic therapy. Methods: In a double-blind randomised investigation flupirtine and paracetamol were given in two consecutive attacks of episodic tension-type headache. 30 children, 6–12 years old, were included. Dosage was determined according to age and weight. The children documented the acute headache intensity and duration in a special diary. Results: Headache intensity was reduced during 2 h after intake in 89% of the 19 children treated. The reduction was 6,5 to 3,1 for flupirtine and 6,9 to 3,3/10 for paracetamol. There was no statistically significant difference between the two substances. Relevant side-effects could not be observed. Conclusion: Flupirtine has shown a convincing clinical effect treating acute episodic tension-type headache for children. The substance was well tolerated by the patients. In addition, flupirtine provides a high degree of safety.
    Notes: Zusammenfassung Hintergrund: Etwa 10% aller Schulkinder leiden nach neueren deutschen epidemiologischen Untersuchungen zumindest gelegentlich an Migräne und etwa 50% an Kopfschmerzen vom Spannungstyp. Häufig nehmen sie bei Spannungskopfschmerzen analgetische Monosubstanzen wie Paracetamol, Azetylsalizylsäure oder Ibuprofen ein. Bei nicht ausreichender Wirkung bzw. Unverträglichkeit besteht Bedarf nach weiteren Substanzen für die Akutanwendung. Methode: In einer doppelblindrandomisierten und gekreuzten Anordnung wurden Paracetamol bzw. das analgetisch und muskelrelaxierend wirksame Flupirtin 30 6- bis 12jährigen Kindern für 2 episodische Spannungskopfschmerzattacken angeboten. 10 Kinder benötigten nach dem Erstkontakt keine Medikation mehr, 1 Kind lehnte die Einnahme grundsätzlich ab. Ergebnisse: Die Kopfschmerzstärke verringerte sich laut Kopfschmerztagebuch innerhalb von 2 h nach der Einnahme auf einer numerischen Schmerzskala (0–10) von 6,5 auf 3,1 unter Flupirtin und von 6,9 auf 3,3 unter Paracetamol bei 89% der verbliebenen 19 Kinder. Statistisch signifikante Unterschiede zwischen beiden Substanzen bestanden nicht. Als Nebenwirkung trat 1-mal Erbrechen unter Paracetamol auf. Schlussfolgerung: Flupirtin hat sich in der Akutphase von episodischen Spannungskopfschmerzen beim Kind bewährt. Es verfügt über eine gute Verträglichkeit. Im Vergleich zu Paracetamol scheint v.a. bei akzidenteller Überdosierung eine größere Sicherheit zu bestehen.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Der Schmerz 14 (2000), S. 302-308 
    ISSN: 1432-2129
    Keywords: Schlüsselwörter Schmerzmessung ; Diagnostik ; Instrumente ; Neugeborene ; Kinder ; Keywords Pain ; Measurement ; Assessment ; Instruments ; Neonates ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background. The assessment and measurement of pain is essential in the implementation and control of pain relieving strategies. The measurement of pain in infants and children should be based on the consideration of age, cognitive level, psychological status, intercurrent diseases and the social context in order to register the child's individual situation and to avoid misinterpretation. Diagnosis. In the preverbal infant, behavioral and physiological cues have to be interpreted by the caregivers. For the assessment of pain in children of four and older who have at least a basic understanding of the pain concept self assessment methods (as rating scales, specific pain interviews, diaries and questionnaires) can be used. In any case the instruments used should be age appropriate. The instruments used for the different age groups are presented with comments on quality and clinical applicability.
    Notes: Zusammenfassung Hintergrund. Voraussetzung zur Durchführung und Kontrolle einer adäquaten und effektiven Schmerztherapie sind die Erfassung und Quantifizierung des Schmerzes in seinen verschiedenen Dimensionen. Bei der Diagnostik des Schmerzes im Kindesalter müssen Alter, kognitiver Entwicklungsstand, psychologischer Status, interkurrierende Erkrankungen und der soziale Kontext berücksichtigt werden, um das Kind in seiner individuellen Situation erfassen zu können und Fehleinschätzungen zu vermeiden. Schmerzdiagnostik im Kindesalter. Im präverbalen Alter werden die physiologischen und verhaltensbezogenen Schmerzäußerungen von Neugeborenen, Säuglingen und Kleinkindern durch eine Fremdbeurteilung erfasst. Bei Kindern ab etwa 4 Jahren, die über ein einfaches Verständnis von Schmerz verfügen, sind Verfahren der Selbsteinschätzung wie einfache Ratingskalen, spezifische Schmerzinterviews, Tagebücher und Fragebögen die primär einzusetzenden Instrumente. In jedem Fall sollten die Instrumente altersgerecht gestaltet sein. Für die verschiedenen Altersgruppen werden Instrumente der Schmerzerfassung mit qualitativen Hinweisen auf deren Güte und klinische Anwendbarkeit vorgestellt.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Der Schmerz 14 (2000), S. 319-323 
    ISSN: 1432-2129
    Keywords: Schlüsselwörter Schmerz ; Kinder ; Impfung ; Verbrennung ; Injektion ; Keywords Pain ; Children ; Vaccination ; Burn ; Injection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Phenomenon pain. While pain is one of the main reasons for an unscheduled visit to the paediatrician, pain due to painful procedures is of major importance in scheduled visits. Actual pain therapy is illustrated in the treatment of burns. Incomplete analgesia may have an unfavourable impact on morbidity and mortality. The pain score does not correlate with the extent of the burned area, and is regularly underestimated. General anaesthesia or analgo-sedation are warranted during the care of the burned patient. Unsufficient analgesia. Consequence of insufficient analgesia during primary care is an increased need of analgesics, and an increased pain treatment failure rate during subsequent procedures. Pain is interfering with anxiety, sleep disturbancies and post-tramatic psychologic alterations. All those symptoms must be treated adequately. Acute illness and injections. This article covers pain from otitis media, pharyngitis, Guillain-Barré syndrome, purpura fulminans, Toxic Epidermal Nekrolysis, as well as the usage of local anaesthesia during injections, not to forget the application of non-pharmacologic methods for pain therapy and prophylaxis.
    Notes: Zusammenfassung Phänomen Schmerz. Das Phänomen “Schmerz” begleitet fast alltäglich den Kontakt zwischen Arzt und krankem Kind. Auf der einen Seite sind Schmerzen der häufigste Grund für eine ungeplante Kinderarztkonsultation, auf der anderen Seite sind bei geplanten Kinderarztbesuchen häufig schmerzhafte Prozeduren durchzuführen. Anhand der starken Schmerzen bei den im Kleinkindalter häufigen Verbrennungen werden schmerztherapeutische Prinzipien konkretisiert: Schmerztherapeutische Prinzipien. Unzureichende Analgesie kann Morbidität und Mortalität ungünstig beeinflussen. Das Schmerzmaß korreliert nicht mit der Ausdehnung der Verbrennung und wird vom Behandler regelmäßig unterschätzt. In vielen Fällen der Erstversorgung sind Allgemeinanästhesie oder Analgosedierung gerechtfertigt, ähnliches gilt für den Verbandwechsel. Ungenügende Analgesie bei der Erstversorgung führt zu erhöhtem Analgetikaverbrauch und schmerztherapeutischen Misserfolgen bei Folgeeingriffen. Wechselwirkungen zwischen Schmerzen und anderen Symptomen wie Angst, Schlafstörungen oder postraumatischen psychischen Veränderungen sind zu beachten und adäquat zu therapieren. Akute Erkrankungen + Injektionen. Weiter wird auf Schmerzen bei Otitis media, Pharyngitis, Guillain-Barré-Syndrom, Purpura Fulminans und Toxischer Epidermaler Nekrolyse sowie den Einsatz von Lokalanästhetika bei Injektionen eingegangen. Schließlich haben auch nicht pharmakologische Methoden ihren Platz in Schmerztherapie und Prophylaxe.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Der Schmerz 14 (2000), S. 333-339 
    ISSN: 1432-2129
    Keywords: Schlüsselwörter Postoperative Schmerztherapie ; Schmerz ; Kinder ; Jugendliche ; Analgetika ; Keywords Postoperative pain therapy ; Pain ; Children ; Adolescents ; Analgesics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Treatment of pain. Undertreatment of postoperative pain in children is a problem in clinical practice. This is due to a lack of both knowledge about age-specific aspects of physiology and pharmacology, and routine pain assessment. For example, the fear of side-effects prevents the adequate usage of opioids. It is of major importance to select a route of drug administration where the child feels comfortable with (avoid intramuscular injections). Non-opioid analgesics. Non-opioid analgesics are recommended for basic pain treatment after minor surgical procedures. Instead of using the whole multitude of drugs available, the doctor should stick to those drugs he is familiar with (acetaminophen, ibuprofen, diclofenac, dipyrone). Opioids. Opioid usage requires individual dose titration and careful monitoring of side-effects (respiratory monitoring, sedation score). The strong opioids piritramide and morphine may advantageously be administered as either continuous, or patient-controlled iv- infusion (PCA). Forms of therapy. In addition to infiltration anesthesia, intraoperatively applied nerve blocks provide excellent pain relief. Epidural analgesia with local anesthetics and/or opioids via a thoracic or lumbar epidural catheter is a therapeutic option after thoracic or abdominal surgery, or after extensive orthopedic or urological interventions. Adjuvant analgesics and nonpharmacologic interventions, i. e. transcutaneous electrical nerve stimulation (TENS), are primarily indicated in patients suffering from neuropathic pain. Conclusion. The establishment of pain services and the comprehensive education of both the nursing and the medical staff should help to improve postoperative pediatric pain therapy.
    Notes: Zusammenfassung Schmerztherapie bei Kindern. Postoperative Schmerzen bei Kindern werden häufig wegen mangelnder physiologischer und pharmakologischer Kenntnisse und des Fehlens einer regelmäßigen standardisierten Schmerzmessung noch immer unzureichend behandelt. Die Angst vor Nebenwirkungen verhindert eine adäquate Opioidtherapie. Bei der Verwendung von Analgetika ist auf eine kindgerechte Applikationsweise (keine i.-m.-Injektionen!) zu achten. Nichtopioidhaltige Analgetika. Nichtopioidhaltige Analgetika (Parazetamol, Ibuprofen, Diclofenac, Metamizol) sind zur Basisschmerztherapie bei kleineren schmerzhaften Eingriffen geeignet. Opioide. Opioide müssen nach Wirkung titriert werden; Nebenwirkungen können nur bei sorgfältigem Monitoring von Atmung und Sedierungsgrad frühzeitig erkannt werden. Opioide (Tramadol, Piritramid, Morphin) können entweder kontinuierlich i. v. oder mittels PCA-Pumpe verabreicht werden. Therapieformen. Neben der Oberflächenanästhesie sind intraoperativ angelegte Nervenblockaden effektive therapeutische Möglichkeiten. Eine lumbale und thorakale Periduralanästhesie mittels Lokalanästhetika und/oder Opioiden bietet sich bei thorakoabdominalen Eingriffen an. Koanalgetika werden vornehmlich bei Nervenschmerzen verwendet und richten sich gegen die schmerzverursachende Pathophysiologie. Optimierung der Schmerztherapie. Die postoperative Schmerztherapie bei Kindern kann durch Einrichtung eines Akutschmerzdiensts und kontinuierliche Weiterbildung von Pflegepersonal und Ärzten optimiert werden.
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  • 12
    ISSN: 1432-2277
    Keywords: Key words Small bowel transplantation ; Monoclonal antibody ; Rat ; Rejection ; Flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study assessed the effect of an anti-rat CD4 monoclonal antibody (OX38) on heterotopic small bowel allograft rejection. Fully allogeneic small bowel transplants were performed in the PVG-to-DA-rat strain combination. Animals received either i) short course (days –1, 0 and 1) of 1 mg/kg per day OX38, ii) short course of 5 mg/kg per day or iii) extended course (days –2, –1, 0, 1, 2 and twice weekly thereafter) of 1 mg/kg per day. Both the high dose (13 days) and extended low-dose (12 days) courses prolonged graft survival compared to untreated control animals (7 days). The low-dose, short-course treatment had no effect. Similar regimens were given to animals that did not receive transplants and in which peripheral blood CD4+ cell counts fell to between 20 and 55 % of pretreatment levels and 20–30 % of binding sites were blocked. In summary, anti-CD4 monoclonal antibody therapy delayed rejection of rat small bowel allografts; however, long-term survival was not achieved.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 14 (2000), S. 1016-1021 
    ISSN: 1432-198X
    Keywords: Key words Nephrocalcinosis ; Sonography ; Renal function ; Body growth ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We carried out a retrospective survey on 152 children and adolescents with nephrocalcinosis (NC) in 22 German centers of pediatric nephrology. Etiology, clinical manifestations, growth and development, sonographic appearance of NC and renal function were analyzed. The median age at the time of diagnosis was 3.3 (range 0.1–21) years and the median duration of follow-up was 4.1 years. In 34% of children NC was associated with idiopathic hypercalciuria (IHC) and in 32% with various hereditary tubular disorders. In 9% NC was observed subsequent to prophylactic bolus administration of vitamin D in infancy. A positive family history was found in 36%. Clinical manifestations were mainly failure to thrive during the 1st year of life (46%), psychomotor/mental retardation (28%) and urinary tract infection (34%). In 14% nephrolithiasis was associated. During the follow-up the proportion of patients with the most severe degree of NC (stages 2b or 3) increased from 40% to 55% and that of hypercalciuria decreased from 79% to 52%. Body height was 〈2 standard deviation scores (SDS) of normal in 41% at the time of diagnosis and in 32% at the last observation; the increase in relative height was significant only for IHC. Glomerular filtration rate (GFR) and urinary concentration capacity changed only slightly with time. At the last investigation GFR was 〈50 ml/min/1.73 m2 in 6% and concentration capacity 〈800 mosmol/kg in 48% of patients. The degree of NC was negatively correlated with GFR and concentration capacity.
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  • 14
    ISSN: 1432-198X
    Keywords: Key words Metabolic acidosis ; Growth ; Growth hormone ; Insulin-like growth factor-I ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Growth impairment induced by chronic metabolic acidosis is associated with an abnormal growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. To examine the potentially beneficial effects of IGF-I on acidosis-induced growth impairment and the influence of GH and IGF-I treatment on the GH/IGF-I axis, three groups of acidotic young rats (untreated, AC, n=12; treated with recombinant human GH, GH, n=8; treated with recombinant human IGF-I, IGF-I, n=8) were studied, and compared with nonacidotic rats fed ad libitum (C, n=9)) or pair-fed with the AC group (PF, n=12). After 14 days of acidosis and 7 days of treatment, growth rate, hepatic abundance of 4.7-kilobase (kb) and 1.2-kb GH receptor transcripts and 7.5-kb and 1.8- to 0.8-kb IGF-I transcripts, serum GH-binding protein (GHBP), and IGF-I concentrations (mean±SEM) were analyzed. Significant decreases of 4.7-kb GH receptor [26±2 vs. 49±6 arbitrary densitometry units (ADU)] and 7.5 kb IGF-I (41±3 vs. 104±10 ADU) transcripts and low serum GHBP (25±1 vs. 32±1 ng/ml) and IGF-I (279±50 vs. 366±6 nmol/l) levels were found in the AC compared with the C rats. The majority of these alterations were also observed in PF rats. Compared with acidotic untreated rats, GH and IGF-I therapy produced no improvement in growth rate. GH treatment normalized the levels of IGF-I mRNA, aggravated the acidosis-related inhibition of the GH receptor gene, and did not modify the serum levels of GHBP and IGF-I. In contrast, IGF-I administration depressed the hepatic expression of all GH and IGF-I transcripts and normalized serum IGF-I concentrations. Our results confirm that sustained metabolic acidosis alters the GH/IGF-I axis, in part because of associated malnutrition, and induced growth retardation that is resistant to GH therapy. Our study also shows that administration of IGF-I does not accelerate the growth of acidotic rats, suggesting a peripheral mechanism, at the level of target tissues, is responsible for the resistance to the growth-promoting actions of GH and IGF-I.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 15 (2000), S. 302-316 
    ISSN: 1432-198X
    Keywords: Key words Calcium channel blockers ; Children ; Pharmacokinetics ; Hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The calcium channel blockers (CCBs) are a diverse group of antihypertensive medications with variable pharmacokinetics and clinical effects. Although CCBs have been widely applied to the treatment of hypertensive children, data regarding the pharmacokinetics, efficacy and safety of these agents in children are extremely limited. In this review we briefly summarize the mechanism of action of CCBs and then summarize pertinent pharmacokinetic information on each of the CCBs commonly used in children, including amlodipine, diltiazem, felodipine, isradipine, intravenous nicardipine, nifedipine and verapamil. Clinically important drug interactions and adverse effects are discussed, as well as the potential role of CCBs in renal protection. Available pediatric efficacy and safety data are summarized, and recommendations made regarding the rational use of CCBs in the management of pediatric hypertension.
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  • 16
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    Pediatric nephrology 15 (2000), S. 57-59 
    ISSN: 1432-198X
    Keywords: Keywords X-linked hypophosphatemia ; Dipyridamole ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  X-linked hypophosphatemia (XLH) is characterized clinically by rickets, hypophosphatemia and hyperphosphaturia. Conventional treatment of XLH with oral phosphate and vitamin D is associated with hypercalcuria and nephrocalcinosis. Recently, intravenous and oral dipyridamole has been reported to decrease fractional excretion of phosphate in adults with idiopathic hyperphosphaturia. Our objective was to determine whether oral dipyridamole therapy reduces urinary phosphate excretion and increases serum phosphate concentration in children with XLH. A prospective study was performed in six children with XLH. The average age of the patients at the start of the study was 12.5±1.0 years. The effects of 12 weeks of oral dipyridamole therapy, at 4.4±0.4 mg/kg body weight per day, on serum phosphorous, parathyroid hormone (PTH), 1,25 (OH)2 vitamin D, osteocalcin, tubular maximum for phosphate reabsorption (TmP/GFR), urinary calcium excretion, and cyclic adenosine 3’,5’-monophosphate (cAMP) excretion, were compared to baseline levels. Our results show that there was no change in serum phosphorous concentration or TmP/GFR after 12 weeks of dipyridamole therapy. Dipyridamole therapy also had no effect on serum PTH, serum 1,25 (OH)2 vitamin D, alkaline phosphatase, osteocalcin levels, urinary calcium or cAMP excretion. We therefore concluded that in children with XLH, a 12-week course of dipyridamole had no effect on serum phosphorous or its urinary excretion. Dipyridamole therapy is unlikely to improve the bone disease in children with XLH.
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  • 17
    ISSN: 1432-198X
    Keywords: Key words Apoptosis ; Ceramide ; Development ; Kidney ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Ceramide is emerging as an important hydrophobic sphingolipid involved in cell differentiation and apoptosis. Since apoptosis plays a significant role in cellular remodeling during renal morphogenesis, we measured ceramide content and apoptosis in the fetal (18 days gestation), neonatal (3, 7, and 14 days postnatal), and adult rat kidney. In addition, to determine whether developmental changes in ceramide content are tissue-specific, we compared renal ceramide content with that in lung and liver. Ceramide was measured by the diacylglycerol kinase assay, and apoptosis was determined by the TUNEL technique. Renal ceramide content fell over 100-fold from the fetus to the 7th postnatal day. Renal apoptosis paralleled ceramide content, with a greater than 300-fold decrease in apoptosis from fetal to adult life. Ceramide content of the lung and liver was significantly less than that of the kidney, and changed less with maturation. We conclude that maturational changes in ceramide content are tissue-specific, and that the high rate of apoptosis in the developing kidney may be related to the elevated ceramide content.
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  • 18
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    Pediatric nephrology 15 (2000), S. 248-251 
    ISSN: 1432-198X
    Keywords: Key words Nephrotic syndrome ; Acute renal failure ; Children ; Peritonitis ; Ischemic tubular necrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Idiopathic acute renal failure (IARF) is an uncommon but severe complication in children with relapsing nephrotic syndrome and may require long-term dialytic support until recovery of renal function takes place. Due to limited understanding of the pathophysiology of IARF, specific guidelines for its prevention and therapy have not been developed. Among triggering factors, peritonitis was present in half of all pediatric patients with this complication described in the English literature over the past 15 years. We report an additional nephrotic child who developed IARF following spontaneous bacterial peritonitis. The renal biopsy showed tubular epithelial changes consistent with acute tubular necrosis. A discussion of related literature and possible pathogenesis of this association is presented.
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  • 19
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    Journal of cancer research and clinical oncology 126 (2000), S. 27-32 
    ISSN: 1432-1335
    Keywords: Key words Heart irradiation ; Plasma enzyme levels ; Myocardial enzyme levels ; Rat ; AbbreviationsCK creatine kinase ; LDH lactate de-hydrogenase ; AST aspartate aminotransferase ; ALT alanine aminotransferase ; α-HBDHα-hydroxybutyrate dehydrogenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Plasma levels of myocardial enzymes present after local heart irradiation were studied in a rat model. The purpose was to investigate whether, within days after irradiation, these enzyme levels change to such an extent that they may be helpful in assessing the severity of cardiac damage after radiotherapy. Therefore, activities of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and α-hydroxybutyrate dehydrogenase (α-HBDH) were determined in the plasma and left ventricular myocardium of rats following local heart irradiation with a single dose of 20 Gy. A dose of 20 Gy is known to cause irreversible cardiac damage and to reduce survival times of the animals. Cardiac enzyme assays were performed directly after and twice daily for up to 2 weeks after radiation. Plasma CK, LDH, AST and α-HBDH levels were increased between 2 h and 24 h after irradiation. Plasma ALT levels remained unchanged. Myocardial enzyme levels, measured between 24 h and 16 days after radiation, did not differ between irradiated and control animals, although acute (first 12 h) reductions were observed in the irradiated group. The elevated enzyme levels in plasma appeared to correlate with the acutely reduced myocardial enzyme levels. Although irradiation with a dose of 20 Gy induced acute rises of cardiac enzyme levels in plasma, it is doubtful that fractionated radiation, as applied clinically for treatment of solid tumors, will induce plasma enzyme elevations that are large enough to indicate the extent of cardiac damage occurring acutely or chronically.
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  • 20
    ISSN: 1433-0350
    Keywords: Key words Child abuse ; Shaken baby syndrome ; Brain injury ; Infants ; Children ; Neuroimaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Acute CT/MRI findings were examined in a prospective, longitudinal study of 60 children 0–6 years of age hospitalized for moderate to severe traumatic brain injury (TBI). TBI was categorized as either inflicted (n=31) or noninflicted (n=29). Glasgow Coma Scale scores and perinatal history were comparable in both groups. Acute CT/MRI studies were visually inspected by a radiologist blind to group membership. Compared with the noninflicted TBI group, the inflicted TBI group had significantly elevated rates of subdural interhemispheric and convexity hemorrhages as well as signs of pre-existing brain abnormality, including cerebral atrophy, subdural hygroma, and ex vacuo ventriculomegaly. Intraparenchymal hemorrhage, shear injury, and skull fractures were more frequent after noninflicted TBI. Subarachnoid hemorrhage and infarct/edema occurred with comparable frequency in both groups. Characteristic acute neuroimaging findings of inflicted TBI included multiple extraaxial hemorrhages in addition to the mild atrophy, subdural hygromas, and ventriculomegaly that suggest prior brain abnormality.
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  • 21
    ISSN: 1433-0350
    Keywords: Key words Brain death ; Children ; Electroencephalogram ; Etiology ; Evoked potentials ; Radioisotopic angiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The objective of this study was to determine the main clinical, neurophysiological and angiographic findings in brain death (BD) in children seen at the Instituto Nacional de Pediatría, a third-level facility in Mexico City, between 1991 and 1996. The following variables were retrospectively analyzed: sex, age, etiology, associated morbidity, duration of stay in hospital, and the results of two of three confirmatory studies (electroencephalogram, evoked potentials, radioisotopic angiography). In all, 125 patients were studied [78 male; median age 2 years (range: 18 days to 17 years)]. The most frequent etiology was infection (34%); 57% of the children developed associated morbidity. In 111 of 122 patients electrocerebral silence was observed; 100 of 107 had brain stem and somatosensory evoked potentials affording conclusive evidence of BD; and 83 of 90 patients had a positive radioisotopic angiography indicating BD. In 76 patients all three confirmatory studies were performed: for 15 there was at least one false-negative test result. Our age cohort showed a predominance of children less than 2 years old. BD etiologies in developing countries differ from those reported in developed countries.
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  • 22
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    Child's nervous system 16 (2000), S. 755-759 
    ISSN: 1433-0350
    Keywords: Keywords Head trauma ; Children ; CT scan ; MRI scan ; Follow-up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  CT scanning is the current first imaging technique to be used after head injury, in those settings where a CT scan is available. The first scan is usually done without contrast enhancement. The value of CT is the demonstration of scalp, bone, extra-axial hematomas and parenchymal injury. It is rapid and easily done in the presence of the multiple monitors that many trauma patients have in place. It can be used to demonstrate the bony anatomy of the spine and is good for evaluation of abdominal and chest trauma also. MRI is more sensitive for all post-traumatic lesions other than skull fracture and subarachnoid hemorrhage, and can demonstrate parenchymal spinal cord injury. The cons are a longer scanning time, interference of the imaging by certain ICP monitors and problems with the positions of the monitoring equipment and ventilators outside the MRI magnetic field. MRI will be used increasingly to study early head injury because of its ability to measure cerebral blood flow, cerebral blood volume and the location and extent of cerebral edema. If the CT does not demonstrate pathology adequate to account for the clinical state, MRI is warranted. Follow up is best done with MRI as it is more sensitive to parenchymal change than is CT.
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  • 23
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    Child's nervous system 16 (2000), S. 451-456 
    ISSN: 1433-0350
    Keywords: Keywords Intracranial pressure ; CSF dynamics ; Infusion test ; Rat ; H-Tx rat ; Outflow resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Although the hydrocephalic H-Tx rat is a widely used model, data on the cerebrospinal fluid (CSF) dynamics in hydrocephalic rats are rare or – as the pressure volume index (PVI) – not available. We used hydrocephalic and nonhydrocephalic H-Tx rats, a stock with a high percentage of inherited hydrocephalus, for the evaluation of such data. In addition, a new, simple mathematical algorithm (”dynamic infusion test”), which has not formerly been used in animal experiments, was used as a pathophysiological model of CSF dynamics. Compared with classical methods for evaluation of these data, the dynamic infusion test gives a deeper insight into the relation between ICP and CSF dynamics. It was found that the resistance to outflow (ROF) in hydrocephalic rats was at least twice that in nonhydrocephalic rats. The PVI measured was similar in hydrocephalic and nonhydrocephalic animals, but clearly higher than the values reported in the literature. This may be attributable to the fact that the classically used bolus test, in contrast to the ”dynamic infusion test”, is representative only for the CSF compartment which is directly exposed to the bolus application.
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  • 24
    ISSN: 1433-044X
    Keywords: Schlüsselwörter Thoraxtrauma ; Atelektasen ; Pädiatrie ; Bauchlage ; Keywords Thoracic trauma ; Atelectasis ; Children ; Prone position
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract We report on the ventilation in prone position in a 5-year-old traumatized child with severe thoracic and abdominal injuries (lung contusion, rib fractures, rupture of liver and spleen). Under continuous analgosedation, the young patient was ventilated in prone position for 6 h, since acute lung injury and atelectasis persisted despite various therapeutic measures (artifical ventilation in the pressure controlled mode, fiberoptic bronchoscopy, reexpansion maneuver). After initiation of the prone position, we observed a rapid increase i narterial oxygenation, which persisted in the following period. The hemodynamic situation remained stable. The complete disappearance of atelectasis was demonstrated radiologically after supine repositioning. After cessation of analgosedation, the extubation was performed 2 days later. Furthermore, we found no side effects of the prone position on the injured abdomen, and the liver function improved rapidly. Although there is a lack of experience with ventilation in prone position in pediatric intensive care, our report might be a recommendation for the indication of this technique in children.
    Notes: Zusammenfassung In dieser Kasuistik wird über die erfolgreiche Anwendung der Beatmung in Bauchlage bei einem 5-jährigen Mädchen berichtet, welches von einem Pkw überrollt worden war und sich Thorax- und Abdominalverletzungen (Rippenserienfraktur, Lungenkontusion, Leber- und Milzeinrisse) zugezogen hatte. Wegen des akuten Lungenversagens mit persistierenden Atelektasen, die durch wiederholte fiberoptische Bronchiallavagen und durch Reexpansionsmanöver nicht zu beheben waren, wurde der Entschluss zur 6-stündigen Lagerung auf den Bauch gefasst, obwohl über den Effekt dieser Lagerungsmaßnahme bei traumatisierten Kindern wenig bekannt ist und zu möglichen negativen Auswirkungen auf das schwerverletzte Abdomen eine Informationen vorliegen. Die Beatmung in Bauchlage führte zur raschen Verbesserung des pulmonalen Gesaustausches, die hämodynamische Situation wurde nicht beeinflusst. Die radiologische Kontrolle nach Rücklagerung zeigte eine vollständigen Rückgang der Atelektasen; die kleine Patientin konnte bald darauf extubiert werden. Weder laborchemisch noch klinisch wurde ein schädigender Einfluss auf das verletzte Abdomen gefunden. Die Beatmung in Bauchlage hat sich als Routineverfahren bei der Behandlung des Lungenversagens des Erwachsenen etabliert; nach der hier beschriebenen Erfahrung ist diese Maßnahme auch bei traumatisierten Kindern in Betracht zu ziehen, insbesondere wenn andere Maßnahmen nicht ausreichend sind.
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  • 25
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Cochlear Implant ; Ambulante Rehabilitation ; Kinder ; Erwachsene ; Ergebnisse ; Keywords Cochlear implant ; Outpatient rehabilitation ; Cost effectiveness ; Results ; Children ; Adults
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background and objective. This study compares the results of the outpatient-based program of the Cochlear Implant Center Ruhr with inpatient-based rehabilitation, which is almost exclusively performed in Germany. Patients/methods. The Department of Otorhinolaryngology at the University of Essen in Germany provided 52 patients with either 22- or 24-channel Nucleus cochlear implants from March 1996 to July 1999. Almost all patients (n=49) were rehabilitated on an outpatient basis, which is the standard in many cochlear implant centers outside Germany. Results. The longest follow-up period at the University of Essen Department of Otorhinolaryngology was 36 months. Minor complications occurred in 10% of the patients. After 24 months, the first three implanted patients were able to discriminate 100% of numbers and over 60% of syllables in the Freiburg speech discrimination test. The patients who developed an understanding of open speech were able to discriminate 31 words per minute with cochlear implant and without lipreading after 24 months. Children were seen to double their Schmid-Giovannini scores at 6 months postimplantation. Conclusions. The Essen outpatient-based cochlear implant program demonstrates results in speech development and speech understanding equal to those of centers providing inpatient rehabilitation. A special advantage is continuous rehabilitation with professionals known to the child for several years. In children especially, exhaustive commuting reduces school attendance and is a burden on the accompanying guardians. As an inpatient, however, the child is torn from his familiar environment. Parents with several children have particular difficulties in accompanying their child and indeed this may not always be possible.
    Notes: Zusammenfassung Hintergrund und Fragestellung. In dieser Arbeit werden die Ergebnisse der ambulanten Rehabilitation nach Cochlear-Implant-Versorgung mit denen der stationären Rehabilitation verglichen, die bisher in Deutschland fast ausschließlich durchgeführt wird. Von März 1996 bis Juli 1999 wurden an der Universitäts-Hals-Nasen-Ohren-Klinik Essen 52 taube oder an Taubheit grenzende Patienten mit einem 22-kanaligen bzw. 24-kanaligen Nucleuscochlear-Implant versorgt. Fast alle Patienten (n=49) konnten wohnortnah ambulant rehabilitiert werden, wie dies dem internationalen Standard entspricht. Ergebnisse. Der längste bisherige Nachbeobachtungszeitraum an der Universitäts-Hals-Nasen-Ohren-Klinik Essen sind 36 Monate. Nach 2 Jahren wurden von den 3 am längsten nachbeobachteten Patienten 100% der Zahlen und über 60% der Einsilber im Freiburger Sprachtest verstanden. Im “speech tracking” erreichten Patienten mit CI und ohne Lippenabsehen nach 24 Monaten 31 Wörter/min. Die Kinder zeigten 6 Monate nach Implantation eine Verdopplung des Scores im Test nach Schmid-Giovannini. Schlussfolgerungen. Das Essener Modell zeigt, dass eine ambulante Rehabilitation nach CI zu vergleichbaren Ergebnissen in der Sprachentwicklung und im Sprachverstehen führt, wie sie von anderen Zentren vorgelegt wurden, in denen fast ausschließlich stationär rehabilitiert wird. Besonders bei Kindern bedeuten lange Anfahrtswege mit einwöchigem stätionärem Aufenthalt Schulausfälle und eine Belastung für die begleitenden Eltern und Familienangehörigen zu Hause, sowie erhebliche Fahrtkosten. Stationäre Aufenthalte zur Rehabilitation reißen zudem das Kind aus seiner gewohnten Umgebung und sind für Eltern mit mehreren Kindern oft unmöglich.
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  • 26
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Hörstörung ; Prävalenz ; Konnatale Hörstörungen ; Erworbene Hörstörungen ; Progredienz ; Infektionen ; Kinder ; Keywords Hearing loss ; Prevalence ; Connatal hearing loss ; Acquired hearing loss ; Progressive hearing loss ; Infections ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The results of international investigations on connatally acquired hearing loss are compared with the data of the German Registry on Childhood Hearing Loss (4058 cases). The connatal hearing disorders have shown a notable change in the last years regarding to aetiology and prevalence. In contrast to countries of the third world in developed nations the prevalence of permanent childhood hearing loss has been reduced down to 1 in 1.000 births. The results let assume a prevalence of approximately 1:1.200 births in Germany. For instance the number of rubella embryopathia decreased effectively. In contrast CMV infections and alcohol fetopathia are playing an increasing role. In the patients of the German Registry on Childhood Hearing Loss the percentage of certainly progressive hearing loss is 10.3 within the 4058 children with permanent hearing impairment. Diagnostic procedures first of all for the early diagnosis of CMV but also of toxoplasmosis are considerable because these infections may result in treatable hearing loss. Also consequent hearing tests are demanded in children with alcohol fetopathia.
    Notes: Zusammenfassung Im vorliegenden Beitrag werden die Daten internationaler Studien zu angeborenen erworbenen Hörstörungen mit den Ergebnissen aus 4058 Fällen im Deutschen Zentralregister für kindliche Hörstörungen (DZH) verglichen und ausgewertet. Die angeborenen Erkrankungen des Hörvermögens haben innerhalb der letzten Jahre bezüglich Ätiologie und Prävalenz einen deutlichen Wandel erlebt. Im Gegensatz zu Ländern der 3. Welt ist die Prävalenz permanenter kindlicher Hörstörungen in den westlichen Industrienationen auf ca. 1:1.000 gesunken. In Deutschland liegt die Prävalenz nach ersten Ergebnissen des DZH bei ca. 1,2:1.000. So ist beispielsweise der Anteil der Rötelnembryopathien stark zurückgegangen. Dagegen spielen heute die Zytomegalievirus-(CMV)-Infektion und die Alkoholfetopathie eine größere Rolle. Im Patientenkollektiv des DZH mit 4058 permanent hörgestörten Kindern beträgt der Anteil gesichert progredienter Verläufe 10,3%. Diagnostische Verfahren, vor allem zur Früherkennung von CMV und Toxoplasmose, gewinnen zunehmend an Bedeutung. Ebenso ist eine konsequente Hördiagnostik auch bei Kindern mit Alkoholfetopathie zu fordern.
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  • 27
    ISSN: 1432-0843
    Keywords: Key words 7-Hydroxymethotrexate ; Methotrexate ; Maximum tolerated dose ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: After more than 50 years of methotrexate (MTX) treatment of acute lymphoblastic leukaemia (ALL), it is currently believed that as long as dose escalations are followed by adequate leucovorin rescue guided by monitoring MTX serum concentrations, hydration and urinary alkalinization, high-dose MTX (HD-MTX) can be tolerated without life-threatening toxicity. However, our recent experimental animal studies of the major metabolite of MTX, 7-OH-MTX, indicate that this concept may have some limitations. Animals with levels of 7-OH-MTX of 1 mM, which is below the levels routinely found in patients on HD-MTX, demonstrate intolerable toxicity and some animals die within 8 h. Electron microscopy indicates that endothelial cell and platelet functions are perturbed. Since animal data are lacking, and interspecies differences not known, we wanted to investigate the maximum tolerated doses of MTX and 7-OH-MTX in a rat model of short-term effects. The maximum tolerated dose was chosen instead of LD50 for reasons of animal welfare. Methods: We infused MTX and 7-OH-MTX into anaesthetized male Wistar rats and monitored the animals for 8 h. The drugs were given as a bolus plus continuous infusion. The dose-finding ranges were 1.8–11.3 g/kg MTX and 0.1–1.2 g/kg 7-OH-MTX. Results: The maximum tolerated dose was between 3 and 5 g/kg for MTX and lower than 0.1 g/kg for 7-OH-MTX. The mean serum concentrations of MTX and 7-OH-MTX in animals that did not survive the 8-h period were 21.9 and 1.6 mM, respectively. The animals that received the highest MTX or 7-OH-MTX doses and concentrations died after sudden reductions in heart rate and blood pressure. Conclusions: We demonstrated a lower maximum tolerated dose of 7-OH-MTX than of MTX in rats after 8 h. The 7-OH-MTX concentrations were in the therapeutic range after HD-MTX. If the rat/human interspecies differences are not large, our data may indicate that HD-MTX regimens should not be further dose intensified, due not so much to the effects of MTX as to those of 7-OH-MTX.
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  • 28
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    Der Anaesthesist 49 (2000), S. 275-278 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Tropisetron ; postoperatives Erbrechen ; Adenotonsillektomie ; Antiemetika ; Kinder ; Key words Tropisetron ; PONV ; Adenotonsillectomy ; Antiemetics ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background: Postoperative nausea and vomiting (PONV) after tonsillectomy is a common problem in children. Tropisetron is a new 5HT3 receptor antagonist and is successfully used in paediatric patients receiving cancer therapy. The aim of the study was to assess efficacy and safety of a single intravenous dose of tropisetron for prevention of PONV in paediatric patients at risk for postoperative vomiting. Methods: In a randomised, double-blind, placebo-controlled trial, we studied 98 children aged 2–12 years undergoing tonsillectomy or adenotonsillectomy. Patients received placebo or tropisetron 0.1 mg (=0.1 ml)/kg body weight immediately after induction of anesthesia. A standard general anesthetic technique (Sevoflurane/N2O/O2 without neuromuscular blockers or opioids) was used. Perioperative vital signs, grade of sedation and episodes of postoperative nausea and vomiting were recorded. Results: No vomiting episodes occurred in 65.3% of the tropisetron treated patients compared to 34.7% of the placebo group (p=0.0024). Only 10.2% of the tropisetron treated patients vomited more than 3 times compared to 22.4% of the control patients (p=0.0004). The need for antiemetic rescue medication was significantly lower in the study group (10.4%) compared to 28.6% (p=0.025). No significant adverse effects of the study medication were shown. Conclusion: A single intravenous prophylactic dose of tropisetron effectively reduces the incidence of PONV during the first 24 postoperative hours after tonsillectomy and/or adenoidectomy. Because of the low incidence of adverse effects, the prophylactic use of tropisetron seems to be safe and justified in paediatric surgical patients at high risk for postoperative vomiting.
    Notes: Zusammenfassung Fragestellung: Erbrechen und Übelkeit nach Tonsillektomien bei Kindern sind ein häufiges Problem. Aufgrund der positiven Erfahrungen mit Tropisetron, einem neueren 5HT3 Rezeptor-Antagonisten bei Chemotherapien in der pädiatrischen Onkologie und mit anderen 5HT3 Rezeptor-Antagonisten in der Kinderchirurgie, prüften wir die Wirksamkeit und Sicherheit einer Einzeldosis Tropisetron zur Prävention von postoperativem Erbrechen bei chirurgischen Kindern mit erhöhtem Risiko für postoperatives Erbrechen. Methodik: Bei 98 Kindern im Alter von 2– 12 Jahren, die eine Tonsillektomie oder Adenotonsillektomie benötigten, führten wir eine randomisierte, doppelblinde, plazebokontrollierte Studie durch. Die Patienten erhielten Tropisetron oder Plazebo in einer Dosis von 0,1 mg (=0,1 ml)/kg KG i.v. unmittelbar nach der Narkoseeinleitung. Die Narkose erfolgte standardisiert mit Sevofluran/N2O/O2 ohne Einsatz von Opioiden und Muskelrelaxanzien. Vitalparameter, Sedationstiefe, das Auftreten von postoperativem Erbrechen und unerwünschte Wirkungen wurden aufgezeichnet. Ergebnisse: In der Tropisetrongruppe zeigten 65,3% der Kinder kein postoperatives Erbrechen, im Gegensatz zu nur 34,7% der Kinder in der Plazebogruppe (P=0,0024). Mehr als 3 Episoden von postoperativem Erbrechen zeigten nur 10,2% der Patienten in der Tropisetrongruppe im Vergleich zu 22,4% der Patienten der Kontrollgruppe (P=0,0004). Auch der Bedarf an antiemetischer Zusatzmedikation war in der Tropisetrongruppe mit 10,4% signifikant niedriger als in der Kontrollgruppe mit 28,6% (P=0,025). Bedeutsame Nebenwirkungen der Studienmedikation konnten nicht dokumentiert werden. Schlussfolgerungen: Eine prophylaktische intravenöse Einzelgabe von Tropisetron reduziert bei Kindern wirksam das Auftreten von postoperativem Erbrechen während der ersten 24 h nach einer Tonsillektomie oder Adenotonsillektomie. Die geringe Inzidenz von Nebenwirkungen rechtfertigt unserer Ansicht nach die prophylaktische Anwendung von Tropisetron bei Kindern nach Tonsillektomien.
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  • 29
    ISSN: 1432-0738
    Keywords: Key wordsα2u-Globulin ; Diethylstilbestrol ; Endocrine disrupter ; Rat ; Screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract α2u-Globulin (AUG) is a major rat urinary protein, which has a molecular weight of 16 kDa (kidney type) or 19 kDa (native type). The biosynthesis of this protein is under multi-hormonal regulation. In this study, we investigated changes in serum AUG level and their association with changes in the reproductive organs of male rats after the administration of the estrogenic chemical, diethylstilbestrol (DES) at doses ranging from 0.01 mg/kg per day to 100 mg/kg per day by gavage for 14 days. Our aim was to establish basic data for the development of a new screening method for endocrine disrupting chemicals based on serum AUG levels. DES treatment decreased the weight of testes in a dose-dependent manner; and was accompanied by atrophic histopathological changes in testes. Testis weights were significantly decreased by the group given 1 mg/kg per day DES; however, histopathological abnormalities were found in the group given 0.1 mg/kg per day DES. In four of five animals in the group given 1 mg/kg per day there was no significant decrease in testis weight and only a slight or moderate degeneration of the pachytene spermatocytes. Despite these findings, serum AUG levels in this group decreased markedly, while the serum AUG level markedly decreased even in the animals with no histopathological change in the 1 mg/kg per day or 0.1 mg/kg per day groups with no histopathological change also showed decreased serum AUG level. These results suggest that the serum AUG level may be a sensitive parameter for detecting the activity of estrogenic chemicals in intact male rats. Although a uterotropic assay has been proposed for immature female or ovariectomized female rats and is currently undergoing validation studies internationally, there is no screening method for estrogenic chemicals in intact male animals. More data on AUG changes by treatment with other estrogenic chemicals are needed in order to determine the sensitivity and specificity of this response to estrogens. Nonetheless, an AUG-based screening test for estrogenic chemicals may be useful owing to its applicability to conventional toxicity studies and an apparently higher sensitivity of this parameter compared to organ weight change or histology of testis in intact male rats and applicability to conventional toxicity studies.
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  • 30
    ISSN: 1432-0738
    Keywords: Key words Flutamide ; Androgen antagonist ; Rat ; Enhanced OECD Test Guideline 407 ; Endocrine disrupters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In association with the international validation project to establish a test protocol for the `Enhanced OECD Test Guideline 407', we performed a preliminary 28-day, repeated-dose toxicity study of flutamide, a non-steroidal androgen antagonist, and assessed the sensitivity of a list of parameters for detecting endocrine-related effects of endocrine-disrupting chemicals (EDCs). Seven-week-old CD(SD)IGS rats were divided into four groups, each consisting of 10 males and 10 females, and administered flutamide once daily by oral gavage at doses of 0 (control), 0.25, 1 and 4 mg/kg body weight/day. Male rats were killed 1 day after the 28th administration. Female rats were killed on the day they entered the diestrus stage in the estrous cycle following the last treatment. Male rats receiving flutamide at dose levels of 1 and 4 mg/kg showed lobular atrophy of the mammary gland and a decrease in epididymal weight. In addition, 4 mg/kg flutamide-treated males exhibited raised serum testosterone and estradiol levels and decreased weight of the accessory sex glands. In females, a slight prolongation of the estrous cycle was also observed in the 4 mg/kg flutamide-treated group. No dose-related changes could be detected by haematology, serum biochemistry and sperm analysis. Thus, among the parameters tested in the present experimental system, the weight of endocrine-linked organs and their histopathological assessment, serum hormone levels, and estrous cycle stage allowed the detection of endocrine-related effects of flutamide.
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  • 31
    ISSN: 1432-119X
    Keywords: Endothelin-A receptor ; Endothelin-B receptor ; Rat ; Pulmonary fibrosis ; Immunohistochemistry ; Quantitative PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: AbstractPulmonary fibrosis is characterized by excessive extracellular matrix deposition with concomitant loss of gas exchange units, and endothelin-1 (ET-1) has been implicated in its pathogenesis. Increased levels of ET-1 from tissues and bronchoalveolar lavage have been reported in patients with pulmonary fibrosis and in animal models after intratracheal bleomycin. We characterized the cellular distribution of alveolar ET receptors by immunohistochemistry in bleomycin-induced pulmonary fibrosis in the rat and determined the regulation by bleomycin of ET receptor mRNA expression in isolated alveolar macrophages and rat lung fibroblasts. We found significant increases in the numbers of fibroblasts and macrophages at day 7 compared to day 28 and control animals. ETB receptor immunoreactivity was observed on fibroblasts and invading monocytes. Isolated fibroblasts expressed both ETA and ETB receptor mRNA, and ETA receptor mRNA was upregulated by bleomycin. Isolated resident alveolar macrophages expressed neither ETA nor ETB receptor mRNA which were also not induced by bleomycin. We conclude that, while ETB receptor stimulation of fibroblasts and monocytes recruited during bleomycin-induced lung injury exerts antagonistic effects on fibroblast collagen synthesis, the observed increase in the number of fibroblasts in vivo and upregulation of fibroblast ETA receptor mRNA by bleomycin in vitro point to a predominance of the profibrotic effects of ET receptor engagement.
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  • 32
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    Experimental brain research 130 (2000), S. 100-104 
    ISSN: 1432-1106
    Keywords: Key words NF-κB ; p65 ; Hippocampal neurons ; Glia ; Astrocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  NF-κB is found in many neuronal cell types in different states of activity. This study aimed to define which conditions induce constitutive NF-κB activity in cultured hippocampal neurons using activity-specific antibody staining. In co-culture with astroglia, hippocampal neurons were devoid of activated NF-κB. In these co-cultures, NF-κB could not be activated via kainate or glutamate. In contrast, separating neurons from the glial compartment resulted in a time-dependent increase of activated neuronal NF-κB. In this line, activation of NF-κB by kainate or glutamate is very effective in freshly separated cultures, but inhibited when the cultures are reassembled after stimulation. These findings suggests that a neuronal-glial interaction may regulate gene expression via NF-κB.
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  • 33
    ISSN: 1432-1076
    Keywords: Key words Coeliac disease ; Children ; Iron deficiency anaemia ; Occult blood ; AbbreviationsCD coeliac disease ; ID iron deficiency ; GFD gluten-free diet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has recently been suggested that in adults with coeliac disease, faecal blood loss may play a role in the development of iron deficiency. A group of 45 children diagnosed with coeliac disease during 1996 and 1997 were therefore prospectively evaluated for the presence of gluten in their diet, iron deficiency anaemia, and faecal occult blood. Sixty children admitted for elective surgery or asthma served as controls. Faecal occult blood was found in four iron deficient children on normal diet, of whom three were newly diagnosed. Occult blood loss disappeared in three of the four children when gluten was removed from their diet. Faecal occult blood was found in 26.7% of children on gluten-containing diet, but not in children on gluten-free diet (P=0.01), or in control children (P=0.001). Conclusion Our data suggest that the incidence of occult blood loss in coeliac disease occurs mainly in newly diagnosed cases and responds to a gluten-free diet. Occult blood testing may not be warranted in the absence of iron deficiency anaemia nor in children with iron deficiency anaemia who are on a gluten-free diet.
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  • 34
    ISSN: 1432-1076
    Keywords: Key words Gentamicin ; Once daily ; Children ; Saliva
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gentamicin is widely used in paediatric medicine and therapeutic monitoring is mandatory due to the narrow margin of safety. Saliva sampling may be of potential interest, especially in children in whom blood sampling is often difficult. Experience with once daily intravenous administration of aminoglycosides has grown in recent years. Gentamicin levels were measured in serum and saliva of 55 children treated with the drug (5 mg/kg per day), administered intravenously in three different regimens: thrice (n=19), twice (n=18), and once daily (n=18). No correlation was found between serum gentamicin concentrations and saliva levels when the drug was administered twice or thrice daily, however, there was good correlation when the drug was administered once daily (r 2=0.96, P 〈 0.0001). Conclusion In children with uncomplicated infections treated with once daily gentamicin, trough concentrations of the drug can be monitored in saliva.
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  • 35
    ISSN: 1432-1076
    Keywords: Key words Sodium cromoglycate ; Children ; Exercise-induced asthma ; Urinary eosinophil protein X excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This double-blind, randomised and cross-over study was designed to compare the preventive effect against exercise-induced bronchoconstriction (EIB), defined as the percentage decrease in FEV1≥15% after 6 min of exercise, of 2 mg and 10 mg of sodium cromoglycate (SCG), administered through a metered dose inhaler via spacer, in asthmatic children. Each of the 30 subject (age 11.6 ± 3.2 years) was tested on five occasions. For inclusion, EIB in test1 was required. In tests 2 to 5, all subjects inhaled 2 mg or 10 mg of SCG 20 min and 120 min before exercise in a randomised order. In order to assess excretion of eosinophil protein X (EPX) accompanying EIB, urine samples were collected before and after exercise. The mean percentage fall in FEV1 (±SD) in test 1 was 26.8 ± 9.8%. Inhalation of 2 mg and 10 mg of SCG 20 min before exercise provided a significant preventive effect in 83% and 77% and inhalation 120 min before exercise provided a preventive effect in 63% and 70%, respectively (n=30). Variance analysis did not reveal a statistically different absolute fall in FEV1 after exercise when both doses (120 min before exercise) were compared (P=0.356). In an unselected subgroup of 12 children, urinary EPX increased after the challenge without SCG premedication (test 1) (mean change: +48.7 μg/mmol creatinine, P=0.034), whereas no significant increase was found in case of SCG premedication (mean change in μg/mmol creatinine): 2 mg/20 min: +12.1; 2 mg/120 min: +8.5; 10 mg/20 min: −10.4 and 10 mg/120 min: −23.5; P 〉 0.1). Conclusion Administration of 10 mg of sodium cromoglycate is no more effective in preventing exercise-induced bronchoconstriction than 2 mg regardless of whether the medication is given 20 or 120 min before exercise. The preventive effect of sodium cromoglycate on exercise-induced bronchoconstriction in asthmatic children is associated with the inhibition of urinary eosinophil protein X excretion.
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  • 36
    ISSN: 1432-1076
    Keywords: Key words Health-related quality of life ; Health status ; Cross-cultural adaptation ; Children ; Health Utilities Index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Steady progress in developing effective treatments for childhood cancer and other severe pediatric diseases has established the need to consider the nature and frequency of late physical and psychological effects. The Health Utilities Index Mark 2 and Mark 3 (HUI2/3) systems were developed by Feeny, Furlong, Torrance et al. in Canada. These systems are generic multi-attribute measures of a person's health status and health-related quality of life. The first German version of the Canadian HUI2/3 questionnaire was created in our clinic, following recommended guidelines for cross-cultural adaptation of health-related quality of life measures. The usefulness of the resultant version was investigated using a sample of 142 patients who presented to our oncological outpatients' department for a routine health care visit after completion of treatment. The 15 items of the HUI2/3-questionnaire were answered independently by three groups of assessors – nurses, physicians, and parents or patients. Two additional questions covered ratings of the severity of treatment effects and the specification of these effects. The questionnaire was both easy to use and acceptable to the assessors. Percentage agreement between observers about levels for individual attributes ranged from 56% to 100%, with the lowest agreement on the subjective attributes of emotion, pain and cognition. These results are in accordance with previous studies using the original instrument. HUI2 global utility scores were significantly related to ratings of treatment sequelae, giving support to the discriminant validity of the measure. Conclusion The German version of HUI2/3 is a useful instrument with generally high inter-observer agreement and good suitability for outcome measurement in childhood cancer patients. Further research is needed to assess the usefulness of the instrument in other clinical populations and its sensitivity in longitudinal studies.
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  • 37
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    European journal of pediatrics 159 (2000), S. 515-519 
    ISSN: 1432-1076
    Keywords: Key words Osteogenesis imperfecta ; Hearing loss ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue. Progressive hearing loss is one of the principal symptoms of OI, affecting about 50% of adult patients. Hearing loss may also occur in childhood and results in additional disability in education and psychosocial adaptation and aggravates the physical handicap. This can be avoided by appropriate otological and audiological treatment. In a nationwide search, 254 Finnish patients with OI were identified indicating a prevalence of 4.9/100 000. Of the 60 children, 45 aged between 4 and 16 years accepting to participate the study on hearing, were evaluated by a questionnaire and clinical audiometry. Hearing loss was defined as pure tone average (PTA0.5–2 kHz) more than 20 dB hearing level (HL). A clinical geneticist determined the type of OI among the 45 patients. Two sporadic OI cases with conductive hearing loss were ascertained (4.4%): An 11-year-old girl with type IV OI with a PTA0.5–2 kHz of 35/40 dB HL and a 15-year-old boy with type IV OI with a PTA0.5–2 kHz of 27/18 dB HL. In addition, a 6-year-old girl with familial OI type I had either a congenital sensorineural deafness or early progressive deafness with PTA0.5–2 kHz of 97/103 dB HL, probably of unrelated aetiology. Conclusion Hearing loss in children with osteogenesis imperfecta is less frequent than generally suspected. Nevertheless, it is recommended that audiometry is performed in children with osteogenesis imperfecta even without symptoms of hearing loss at the age of 10 years, and repeated every 3 years thereafter.
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  • 38
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    European journal of pediatrics 159 (2000), S. 430-433 
    ISSN: 1432-1076
    Keywords: Key words Alport syndrome ; Angiotensin-converting enzyme inhibitors ; Proteinuria ; Children ; AbbreviationACEi angiotensin-converting enzyme inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Enalapril, a long-acting inhibitor of angiotensin-converting enzyme, was given for 2 years to seven children with Alport syndrome. Five patients had a classical X-linked form of the disease; two siblings had the autosomal recessive variant. Their age was between 5.15 and 13.75 years when enalapril was started. All patients had haematuria and proteinuria, creatinine clearance was 〉80 ml/min per 1.73 m2 in all, and only one patient was hypertensive. The starting dose of enalapril (0.1 mg/kg body weight per day) was increased progressively according to individual clinical tolerance. The median doses were 0.13, 0.12, 0.21 and 0.29 mg/kg at 6, 12, 18 and 24 months, respectively. Median values of mean blood pressure were 95 mmHg at the start and 84 mmHg after 24 months. Median daily proteinuria decreased from 52 mg/kg to 18 mg/kg at 6 months, 21 mg/kg at 12 months, 12 mg/kg at 18 months and 30 mg/kg at 24 months. Serum creatinine increased over time from a median of 0.64 mg/dl at baseline to 0.77 mg/dl at 24 months. Concomitantly, there was a decrease in GFR from 104 to 83 ml/min per 1.73 m2 at 18 months and an increase again to 95 ml/min per 1.73 m2 at 24 months. Analysis of the individual data showed three patterns: no response (n=2), temporary response (n=2) and sustained response (n=3). Conclusion When given enalapril at the dosages mentioned, Alport patients as a group display a marked reduction in urinary protein excretion with a nadir of 23% of the baseline figure at 18 months, a decrease that cannot be accounted for by the slight decrease in glomerular filtration rate. Although these are preliminary data, it is recommended to try an angiotensin-converting enzyme inhibitor in every paediatric Alport patient with proteinuria.
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  • 39
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    European journal of pediatrics 159 (2000), S. 575-578 
    ISSN: 1432-1076
    Keywords: Key words Haemophilia ; HIV-negative patients ; Children ; Growth ; Body mass index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been shown that HIV-positive haemophilic children develop growth retardation. As not only the HIV infection but also other disease-related factors might compromise growth in these children, growth data were analysed in a longitudinal cross-sectional manner in 84 HIV-negative haemophilic patients from two university clinics. A total of 2–24 height and weight measurements (median 6) were recorded in each patient resulting in 683 single values collected between 1977–1995. Height SDS of all haemophilic boys was −0.31 ± 2.13 (mean ± SD, NS versus 0) and body mass index SDS was 0.21 ± 3.49 (mean SD, NS versus 0) at first measurement and remained unchanged throughout the observation period. Neither height nor body mass index differed with respect to the severity of haemophilia (mild/moderate/severe) or the study centre (Vienna/Prague). Conclusion Growth in HIV-negative patients with haemophilia is not affected in spite of the immunological abnormalities attributed to the substitution therapy or the bleeding episodes in the joints with the potential effect on the growth plate.
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  • 40
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    European journal of pediatrics 159 (2000), S. 649-656 
    ISSN: 1432-1076
    Keywords: Key words Antiretroviral therapy ; Children ; AIDS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The introduction of combination antiretroviral therapy has been associated with a dramatic clinical improvement in children with human immunodeficiency virus infection. However, the uptake of antiretroviral therapy has been variable across Europe. The Paediatric European Network for the Treatment of AIDS Steering Committee has performed a systematic literature review of paediatric antiretroviral therapy trials. An analysis of the evidence base for the commencement and maintenance of antiretroviral therapy was produced. Suggestions for when to commence antiretroviral therapy, which drugs to start with and how to monitor and sequence drug regimens are given. Conclusion The aim of these guidelines is to help in obtaining equity of access to a uniformly high standard of care for children with human immunodeficiency virus infection in all European countries.
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  • 41
    ISSN: 1432-1076
    Keywords: Key words Insulin aspart ; Insulin analogue ; Type 1 diabetes ; Pharmacokinetics ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics of the novel, rapid-acting insulin aspart were compared with those of soluble human insulin following subcutaneous administration in nine children (aged 6–12 years) and nine adolescents (aged 13–17 years) with stable type 1 diabetes. The study had a randomised, double-blind, two-period crossover design. Each patient received a single subcutaneous dose of insulin aspart or human insulin (0.15 IU/kg body weight) 5 min before breakfast and the plasma insulin and glucose concentrations were measured at intervals during the following 5 h. The pharmacokinetic profile of insulin aspart differed significantly from that of human insulin with a higher mean maximum serum insulin (Cmax ins), 881 ± 321 (SD) pmol/l versus 422 ± 193 pmol/l for human insulin (P 〈 0.001); and with a shorter median serum insulin t max ins, 40.0 min (interquartile range: 40–50 min) versus 75.0 min (interquartile range: 60–120 min) for human insulin, (P 〈 0.001). An age-related effect on Cmax ins and area under the curve (AUC0–5h ins) was observed with higher values in adolescents than in children for both insulin aspart and human insulin. Postprandial glycaemic control was improved with insulin aspart; the baseline-adjusted ΔCmax glu being lower for insulin aspart compared with human insulin (increase of 7.6 ± 5.1 versus 9.4 ± 4.4 mmol/l respectively, P 〈 0.05). The incidence of adverse events was similar for the two insulin types. Conclusion The more rapid onset of action of insulin aspart versus human insulin, previously observed in adults, is confirmed in a paediatric population with type 1 diabetes.
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  • 42
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    European journal of pediatrics 159 (2000), S. 507-508 
    ISSN: 1432-1076
    Keywords: Key words Behçet disease ; Children ; Myositis ; Pustulosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 12-year-old boy presented with a limp and findings suggesting localised myositis of his right calf and a working diagnosis of Behçet disease was made. During 3 years of follow-up, he had another three episodes of calf myositis, all responsive to corticosteroids within days. Conclusion A case of recurrent localised myositis as a main manifestation of Behçet disease is reported. The evolution of incomplete Behçet disease, which is common in children, to the full blown form, with the emphasis on muscle involvement and the importance of early diagnosis of Behçet disease, is discussed.
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  • 43
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    European journal of pediatrics 159 (2000), S. 530-534 
    ISSN: 1432-1076
    Keywords: Key words Schistosomiasis ; Children ; Travellers ; Ultrasonography ; Immunodiagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Reports on schistosomiasis in children growing up in Europe are rare despite increased travel activity. We report on eight male and three female German children aged 50 months to 15 years with schistosomiasis. Six children were asymptomatic, whereas two presented with typical signs of Katayama fever. Persisting haematuria, headache with eosinophilia and pyelonephritis were observed in one child each. An exposure was reported for six of the children. Two were examined solely because schistosomiasis was diagnosed in a family member. All had antibodies against schistosomal antigens in at least two of three screening tests. However, schistosomal ova (Schistosoma haematobium) were detected in urine and faecal specimens from only three children. A tumour-like lesion of the bladder was found by ultrasound in only one of the children who also exhibited haematuria. Neither eosinophilia nor elevated IgE levels were constant findings. Six to 12 months after praziquantel treatment, parasitological and ultrasound checks were negative and levels of specific antibodies decreased. However, 2 years later, elevated antibody levels were detected in one girl without evidence of any new exposure. She became antibody-negative 1 year after a second course of treatment. Conclusion In contrast to residents of endemic areas, parasitological and ultrasound examinations seem to be inferior to immunodiagnostics in children from non-endemic areas at temporary risk for schistosomiasis.
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  • 44
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    Der Hautarzt 51 (2000), S. 95-100 
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Dubowitz-Syndrom ; Atopisches Ekzem ; Monozygote Zwillinge ; Kinder ; Keywords Dubowitz syndrome ; Atopic eczema ; Monozygotic twins ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Autosomal recessive inheritance, intrauterine growth retardation, short stature, microcephaly, distinct facial dysmorphism, psychomotoric retardation, and often uncharacterized eczematous skin lesions distinguish the rare Dubowitz syndrome. Here a pair of monozygotic twins with Dubowitz syndrome and clear-cut atopic eczema is presented.
    Notes: Zusammenfassung Autosomal rezessiver Erbgang, intrauterine Wachstumsretardierung, Kleinwüchsigkeit, Mikrozephalie, charakteristische Gesichtsdysmorphie, psychomotorischer Entwicklungsrückstand sowie häufig nicht näher charakterisierte ekzematöse Hautveränderungen kennzeichnen das seltene Dubowitz-Syndrom. Wir berichten über monozygote Zwillinge mit Dubowitz-Syndrom und eindeutigem atopischen Ekzem.
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  • 45
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Atopisches Ekzem ; Kinder ; Elternschulung ; Video ; Mütter ; Key words Atopic eczema ; Parental education ; Video ; Children ; Mothers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background and Objective. Psychological problems in children and parents related to children's atopic eczema (AE) may impede the success of treatment. We studied the question, if behavior-based parental education in groups (DPE) or standardized video-education (VPE) could enhance dermatological treatment effects and reduce skin-damaging behaviors in children and stress in their mothers. Patients/Methods. 47 mothers attending the university outpatient-clinic for dermatology and their AE-children (mean age 4 years) participated in the study. 18 mothers underwent the DPE (10 sessions), 15 mothers worked with VPE at home. Dermatological standard treatment (CG; N=14) served as control for a 16-weeks-evaluation-period. Results. AE-symptoms improved overall, but the effectiveness of the treatments differed significantly, improval with parent education and was best with VPE. Psychological problems of mothers were equally reduced with DPE and VPE. Conclusions. It is suggested that VPE is a cost effective and less time consuming method for supporting dermatological therapy of AE in children.
    Notes: Zusammenfassung Hintergrund und Fragestellung. Das atopische Ekzem (AE) im Kindesalter kann psychologische Probleme bei Kind und Eltern zur Folge haben, die den Behandlungserfolg erschweren. Die Effektivität direkter verhaltensorientierter Elterngruppenschulungen (DES) bzw. standardisierter Videoschulungen (VES) gegenüber der dermatologischen Standardbehandlung (KG) zur Besserung des AE, des Kratzverhaltens der Kinder und krankheitsbedingter Belastungen der Mütter wurde überprüft. Patienten/Methodik. An der Studie nahmen 47 Mütter und deren AE-Kinder (Durchschnittsalter 4 Jahre) aus der Neurodermitisambulanz der Universitätshautklinik teil, 18 Mütter besuchten die DES (10 Gruppensitzungen), 15 Mütter arbeiteten mit der VES zu Hause. Die Behandlung der KG (n=14) erfolgte im vergleichbaren 4-Monats-Zeitraum. Ergebnisse. Das AE war über alle Behandlungsbedingungen gebessert, ihre Effekstärken unterschieden sich jedoch signifikant: Elternschulungen waren effektiver als Standardbehandlung, den stärksten Effekt hatte die VES. Belastungen der Mütter reduzierten sich nach beiden Schulungsformen. Schlussfolgerungen. Die Ergebnisse verweisen auf eine Zeit und Kosten sparende Möglichkeit, Videoschulungen für die Unterstützung der Therapie des AE im Kindesalter zu nutzen.
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  • 46
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Dermatologie ; Primary Health Care ; Langzeitergebnisse ; Kinder ; Kenia ; Keywords Dermatology ; Primary health care ; Long-term effects ; Children ; Kenya
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background and Objective. In spite of the importance of skin diseases in Africa south of the Sahara, dermatology is insufficiently represented within the established primary health care systems. Aim of this study was to find out whether an integrated dermatology project could reduce the prevalence of dermatoses. Patients/Methods. Since 1994 trained community health workers have carried out regular weekly visits to schools and nurseries in 10 communities in rural western Kenya. Epidemiological studies were done in 13 schools in 4 communities involving 5780 and 4961 pupils one year before (1993) and 5 years (1999) following the introduction of the dermatology project. Results. Within this period the prevalence of bacterial skin infections fell from 12.7% to 11.3% (n.s.). Mycoses rose from 10.1% to 13.9% (p〈0.05), while arthropod infections (mainly scabies) remained unchanged with a prevalence of 8.3% in 1993 and 8.0% in 1999 (n.s.). Dermatitis also showed no changes (1.7% in both years). Conclusions. The prevalence of infective dermatoses depends not only on medical treatment but also far more on socio-economic factors.
    Notes: Zusammenfassung Hintergrund und Fragestellung. Trotz der großen Bedeutung der Dermatosen in Schwarzafrika ist die Dermatologie in den dort etablierten Basisgesundheitsdiensten völlig unzureichend repräsentiert. Untersucht werden sollten die Langzeitauswirkungen eines in das Primary Health Care-System integrierten Dermatologieprojekts in Bezug auf die Prävalenz von Hauterkrankungen. Patienten/Methodik. Seit 1994 besuchen ausgebildete Community Health Workers einmal wöchentlich Schulen und Vorschulkindergärten in 10 Gemeinden im ländlichen Westkenia. In 13 Schulen von 4 Gemeinden wurden 1 Jahr vor (1993) und 5 Jahre nach (1999) Projektinitiierung Reihenuntersuchungen an 5780 bzw. 4961 Kindern durchgeführt. Ergebnisse. Innerhalb dieses Zeitraums sank die Prävalenz bakteriell bedingter Dermatosen von 12,7% auf 11,3% (n.s.). Bei den Mykosen fand sich ein Anstieg von 10,1 auf 13,9% (p〈0,05). Arthropodenbedingte Infektionen (vorwiegend Skabies) blieben mit 8,3% 1993 und 8,0% 1999 (n.s.) im Wesentlichen gleich. Ekzeme wiesen zu beiden Zeitpunkten eine Prävalenz von 1,7% auf. Schlussfolgerungen. Die Prävalenz infektiöser Dermatosen hängt nur zu einem geringen Teil von der medizinischen Versorgung, sondern überwiegend von sozioökonomischen Faktoren ab.
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  • 47
    ISSN: 1129-2377
    Keywords: Key words Coeliac disease ; Headache ; Children ; HLA antigens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The linkage between HLA antigens and disease susceptibility has been investigated in several diseases. Two different mechanisms are known to act in the relation between the HLA system and headache: linkage and association of alleles. Among neurological disorders associated with coeliac disease (CD) we focused on headache in 1997. From a group of 70 coeliac children, we studied 10 children with headache (3 boys and 7 girls). For each subject we evaluated clinical history and HLA antigens. The incidence of headache was not different with respect to the prevalence of headache in the general population. The HLA setting is not different between the 2 groups examined. However, we highlight 2 cases for the particular HLA setting.
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  • 48
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    Acta neuropathologica 100 (2000), S. 75-81 
    ISSN: 1432-0533
    Keywords: Key words Fas ; Fas ligand ; Rat ; Spinal cord ; Trauma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This immunohistochemical study evaluated Fas and Fas ligand (FasL) in the rat nervous system and their changes in the spinal cord subjected to compression. Normal spinal cord showed a low level of Fas and FasL immunoreactivity in the white matter except in the corticospinal tracts. Fas and FasL immunoreactivity seemed to be located in axons and their myelin sheaths. Other regions of the nervous system did not show immunoreactivity to Fas and FasL. Moderate and severe compression injury of the spinal cord resulted in a reduction of Fas and FasL immunoreactivity in the white matter of injured T8–9 segments at 4 h and a complete loss at 1 day after trauma. This was seen even in the remaining white matter. In contrast, increased immunoreactivity to Fas and FasL was present in the cranial T7, caudal T10 (moderate injury) and T12 (severe injury) segments at day 4 with most intense staining were seen at day 9 after trauma. Increased Fas and FasL immunoreactivity may have pathophysiological implications for the development of secondary injuries after trauma to the spinal cord. Fas-FasL interactions may for instance be involved in apoptosis of oligodendrocytes which occurs as a delayed phenomenon after trauma to the spinal cord. The integrity of myelin sheaths may in this way be jeopardized by apoptosis of oligodendrocytes.
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  • 49
    ISSN: 1432-0533
    Keywords: Key words Hypothermia ; Immunohistochemistry ; Microtubule-associated protein 2 (MAP2) ; Rat ; Spinal cord injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Systemic hypothermia has been shown to exert neuroprotective effects in experimental ischemic CNS models caused by vascular occlusions. The present study addresses the question as to whether systemic hypothermia has similar neuroprotective qualities following severe spinal cord compression trauma using microtubule-associated protein 2 (MAP2) immunohistochemistry combined with the avidin-biotin-peroxidase complex method as marker to identify neuronal and dendritic lesions. Fifteen rats were randomized into three equally sized groups. One group sustained thoracic laminectomy, the others severe spinal cord compression trauma of the T8-9 segment. The control group contained laminectomized animals submitted to a hypothermic procedure in which the esophageal temperature was reduced from 38 °C to 30 °C. The two trauma groups were either submitted to the same hypothermic procedure or kept normothermic during the corresponding time. All animals were sacrificed 24 h following the surgical procedure. The MAP2 immunostaining in the normothermic trauma group indicated marked reductions in MAP2 antigen in the cranial and caudal peri-injury zones (T7 and T10, respectively). This reduction was much less pronounced in the hypothermic trauma group. In fact, the MAP2 antigen was present in almost equally sized areas in both the hypothermic groups independent of previous laminectomy alone or the addition of trauma. Our study thus indicates that hypothermia has a neuroprotective effect on dendrites of rat spinal cords subjected to compression trauma.
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  • 50
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    The journal of headache and pain 1 (2000), S. 169-172 
    ISSN: 1129-2377
    Keywords: Key words Migraine ; Sleep ; Sleep apnea ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In our previous study we found a high prevalence of disordered sleep breathing in migraine children vs. controls. Since no quantitative studies about sleep respiratory disorders have been carried out in migraine children, we performed a polysomnographic (PSG) study in 10 migraine patients (7 boys, 3 girls; mean age 8.11 years, range, 5.8–14.5) attending the Headache Center of our department, to evaluate the presence of sleep apnea. Mothers completed a headache diary and a sleep diary for at least 1 month and filled out a sleep questionnaire. PSG data showed a normal sleep architecture in 3 cases, an insomnia pattern in 2, a reduction of slow wave sleep in 3 and a reduction of REM sleep in 2. Respiratory analysis revealed that 2 of 10 patients had obstructive sleep apnea. These 2 patients presented habitual snoring and associated sleep disturbances such as restless sleep and hypnic jerks. Sleep apnea may be a subtle and often undiagnosed symptom in several migraine patients. The report of habitual snoring associated with other sleep disturbances such as restless sleep and other parasomnias may be a sign of sleep apnea in migraine children.
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  • 51
    ISSN: 1432-2277
    Keywords: Key words Kidney transplantation ; Rat ; Chronic rejection ; Cytomegalovirus ; Adhesion molecules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have demonstrated that both cytomegalovirus (CMV) infection and prolonged cold ischemia of the allograft (CI) are associated with chronic rejection of renal transplants. The purpose of this study is to investigate the effect of CMV infection, of CI and of the combination of both, on the progression of chronic rejection, and to obtain a more detailed insight in their effects on the expression of adhesion molecules. Therefore, a rat transplantation model was used. Lewis recipients of renal allografts (with and without CI) from MHC-incompatible Brown Norway rats were inoculated with rat CMV or left uninfected. CMV infection alone resulted in an increased influx of CD4+ cells and macrophages early after infection, and in an increase in glomerular sclerosis and intima proliferation. CI caused an increase in infiltrating NK cells and an effect on intimal proliferation, glomerular sclerosis, and tubular atrophy. When CMV infection and CI were combined, an additive effect could be measured. This was however not the case for the function of the kidney. The creatinin showed a synergistic effect of the two influencing factors. Due to the CMV infection, an increase in CD49 d cells was detected. CI resulted in an increase in CD18 cells and an increase in the expression of CD62P on vessels, and CD54 and CD44 on tubules. When CMV infection and CI were combined, all the effects caused by CMV and CI alone were present in an additional way.¶The results of the present study suggest that special attention should be paid to the recipient of an ischemically injured graft when either the donor or the recipient is CMV-infected. The patterns seen in histology, the infiltration of leukocytes and the expression of adhesion molecules, suggest that CI and CMV infection both have an effect on rejection, but act by different mechanisms.
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  • 52
    ISSN: 1432-2072
    Keywords: Keywords Novelty ; Context ; Environment ; Stress ; 6-OHDA ; Rotational behavior ; Striatum ; Nucleus accumbens shell ; Caudate ; Amphetamine ; Dopamine ; Glutamate ; Aspartate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: We have previously shown that environmental novelty enhances the behavioral activating effects of amphetamine and amphetamine-induced expression of the immediate early gene c-fos in the striatal complex, particularly in the most caudal portion of the caudate. In contrast, we found no effect of novelty on the ability of amphetamine to induce dopamine (DA) overflow in the rostral caudate or in the core of the nucleus accumbens. Objectives: The twofold aim of the present study was to determine the effect of environmental novelty on (1) amphetamine-induced DA overflow in the shell of the nucleus accumbens and in the caudal portions of the caudate, and (2) glutamate and aspartate overflow in the caudal portions of the caudate. Methods: Two groups of rats with a unilateral 6-hydroxydopamine lesion of the mesostriatal dopaminergic system received amphetamine (0.5 mg/kg, i.v.) in physically identical cages. For one group, the cages were also the home environment, whereas, for the other group, they were a completely novel environment. In vivo microdialysis was used to estimate DA, glutamate, and aspartate concentrations. Results: Environmental novelty enhanced amphetamine-induced rotational behavior (experiments 1–3) but did not alter amphetamine-induced DA overflow in either the shell of the nucleus accumbens (experiment 1) or the caudate (experiment 2). In addition, the ability of environmental novelty to enhance amphetamine-induced behavioral activation was not associated with changes in glutamate or aspartate efflux in the caudate (experiment 3). Conclusions: The present data indicate that the psychomotor activating effects of amphetamine can be modulated by environmental context independent of its primary neuropharmacological actions in the striatal complex.
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  • 53
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    Psychopharmacology 151 (2000), S. 219-225 
    ISSN: 1432-2072
    Keywords: Keywords Amphetamine ; Wheel running ; Behavioral sensitization ; Pharmacological sensitization ; Novelty ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: This study explored whether repeated injections of amphetamine (AMP), which increase general locomotion, also increase acute wheel running, a highly structured, rewarding, motor behavior not correlated with other locomotor activities. Objectives: The experiments determine how 1–5 mg/kg d-AMP affects wheel running and see if, over repeated injections, the AMP effects show context specific sensitization. Methods: In experiment 1, 2 mg/kg AMP or saline (SAL) was injected on days 1, 3, 6, 8, and 10 to male Sprague-Dawley rats with either limited or no wheel experience. 20 min after the injection animals were tested in an open field for 5 min and then in a running wheel for 1 h. Rats were injected with SAL or AMP on the days following testing. On days 13 and 15, animals were tested for conditioning (following SAL) and sensitization (following AMP). In experiment 2, the effects on wheel running of repeated 1, 2, or 5 mg/kg AMP were tested. Results: In experiment 1, AMP (2 mg/kg) elevated open field ambulation but suppressed wheel running. Limited wheel experience potentiated the AMP-induced suppression. At test, the suppression of running was found to be context specific. In experiment 2, 1 mg/kg did not affect running, while 2 and 5 mg/kg resulted in dose-dependent running suppression. Acquisition and test AMP dose both influenced the running suppression at test; context had a marginal influence. Conclusions: The degree of running suppression induced by repeated AMP is determined by both psychological (the injection context) and pharmacological (the acquisition dose) factors. This AMP-induced running suppression is consistent with the sensitization of stereotyped behavior.
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  • 54
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Drug discrimination ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The cellular effects of nicotine underlying its addictive liability are thought to be mediated by neuronal nicotinic receptors (nACHRs) in the central nervous system. It is believed that densely expressed β2-containing nACHRs in the central nervous system are responsible for these actions, but few data are available that can directly assess subtype mediation of nicotine’s acute subjective and reinforcing effects. Objective: The present study compared the effects of the competitive nACHR antagonist erysodine and the noncompetitive antagonist mecamylamine in rats trained to discriminate or self-administer nicotine. Methods: Adult male rats were trained to disciminate 0.4-mg/kg injections of nicotine from vehicle in a two-lever procedure of food-maintained behavior, or to self-administer 0.03-mg/kg injections of nicotine under fixed-ratio 5 or progressive-ratio schedules of reinforcement. Additional rats were trained under a food-maintained procedure of lever pressing. Results: Erysodine (0.3–10 mg/kg) and mecamylamine (0.1–1.0 mg/kg) blocked nicotine discrimination, although only erysodine produced the rightward shift that would be predicted of a competitive antagonist. Erysodine (0.32–32 mg/kg) and mecamylamine (0.32–3.2 mg/kg) also selectively reduced nicotine self-administration on a fixed-ratio schedule and lowered break points on a progressive-ratio schedule. Conclusions: Based on the known affinity of erysodine for α4β2 nACHRs and its selectivity relative to α7 and α1β1γδ receptors, the present data support a critical role of β2-containing nACHR constructs in the discriminative and reinforcing actions of nicotine.
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  • 55
    ISSN: 1432-2072
    Keywords: Key words Drug discrimination ; Olanzapine ; Clozapine ; Chlorpromazine ; Haloperidol ; Thioridazine ; Raclopride ; Risperidone ; Scopolamine ; Ritanserin ; Atypical antipsychotic ; Neuroleptic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Analysis of the preclinical behavioral effects of atypical antipsychotic agents will provide a better understanding of how they differ from typical antipsychotics and aid in the development of future atypical antipsychotic drugs. Objectives: The present study was designed to provide information about the discriminative stimulus properties of the atypical antipsychotic olanzapine. Methods: Rats were trained to discriminate the atypical antipsychotic olanzapine (either 0.5 mg/kg OLZ or 0.25 mg/kg OLZ, i.p.) from vehicle in a two- lever drug discrimination procedure. The atypical antipsychotic clozapine fully substituted for olanzapine in both the 0.5-mg/kg OLZ group (99.3% drug lever responding [DLR]) and the 0.25-mg/kg OLZ group (99.9% DLR). The typical antipsychotic chlorpromazine also substituted for olanzapine in both the 0.5-mg/kg OLZ group (87.5% DLR) and in the 0.25-mg/kg OLZ group (98.9% DLR); whereas, haloperidol displayed partial substitution for olanzapine in the 0.5-mg/kg OLZ group (56.1% DLR) and in the 0.25-mg/kg OLZ group (76.4% DLR). The 5.0-mg/kg dose of thioridazine produced olanzapine-appropriate responding in the 0.5-mg/kg OLZ group (99.6% DLR), but only partial substitution was seen with the 0.25-mg/kg OLZ training dose (64.0% DLR). The atypical antipsychotics raclopride (53.9% DLR) and risperidone (60.1% DLR) displayed only partial substitution in the 0.5-mg/kg OLZ group. Both the muscarinic cholinergic antagonist scopolamine (90.0% DLR) and the 5-HT2A/2C serotonergic antagonist ritanserin (86.0% DLR) fully substituted for olanzapine in the 0.5-mg/kg OLZ group. Conclusions: In contrast to previous discrimination studies with clozapine-trained rats, the typical antipsychotic agents chlorpromazine and thioridazine and the serotonin antagonist ritanserin substituted for olanzapine. These results demonstrate that there are differences in the mechanisms underlying the discriminative stimulus properties of clozapine and olanzapine. Specifically, olanzapine’s discriminative stimulus properties appear to be meditated in part by both cholinergic and serotonergic mechanisms.
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  • 56
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    Psychopharmacology 148 (2000), S. 243-250 
    ISSN: 1432-2072
    Keywords: Key words Attention ; Scopolamine ; Mecamylamine ; Oxotremorine ; Physostigmine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: This study tried to determine the relative roles of muscarinic and nicotinic cholinergic receptors in attentional processing. Methods: The effects of cholinoceptor agonists and antagonists, and of an anticholinesterase, were studied on performance of rats in a five-choice serial reaction time task. Results: Scopolamine (0.1 mg/kg) and mecamylamine (5.0 mg/kg) produced deficits in accuracy and reaction time, respectively. This may suggest a differential role for the two types of cholinoceptors in information processing. Combinations of sub-threshold doses of scopolamine (0.01–0.03 mg/kg) and mecamylamine (0.5–1.6 mg/kg), which alone did not affect accuracy or reaction time, did not produce significant deficits in attention. However, the pattern of effects after combined treatment suggested that the differential deficits seen with these drugs alone remained. The anticholinesterase physostigmine (0.1 mg/kg) and the non- selective muscarinic agonist oxotremorine (0.03 mg/kg) induced severe behavioural disruption at doses that appeared to be relatively well tolerated in previous studies; this precluded the derivation of accuracy and response time data at these doses. At lower doses, neither physostigmine (0.05 mg/kg) nor oxotremorine (0.003 mg/kg) significantly affected any performance measure; this may reflect the ability of both drugs to indirectly or directly activate presynaptic muscarinic receptors that inhibit acetylcholine release, respectively. Conclusions: Both muscarinic and nicotinic cholinoceptors may be important in attention but they may serve different roles in information processing; this hypothesis could be tested using tasks that place different emphasis on different stages of information processing.
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  • 57
    ISSN: 1432-2072
    Keywords: Key words ACTH ; Corticosterone ; GABA ; Noradrenaline ; Adrenaline ; Stress ; Rat ; Diazepam
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Gabolysat PC60 is a fish protein hydrolysate with anxiolytic properties commonly used as a nutritional supplement. Objective: The diazepam-like effects of PC60 on stress responsiveness of the rat pituitary-adrenal system and on sympathoadrenal activity were studied. Methods: The activity of the pituitary-adrenal axis, measured by plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (B) of the sympathoadrenal complex, measured by circulating levels of noradrenaline (NA) and adrenaline (A), and the gamma aminobutyric acid (GABA) content in the hippocampus and the hypothalamus were investigated in male rats which received daily, by an intragastric feeding tube, for 5 days running either diazepam (1 mg/kg) or PC60 (300 or 1200 mg/kg). Controls received only solvent (carboxymethylcellulose 1%). Six hours after the last force-feeding, the rats were subjected to 3 min ether inhalation or 30 min restraint and killed by decapitation 30 min after ether stress or at the end of restraint. Results: Baseline plasma levels of ACTH, B, NA and A were not affected by either diazepam or PC60. Both ether- and restraint-induced release of ACTH, but not B, were similarly and drastically reduced by diazepam and PC60 (1200 mg/kg). Both diazepam and PC60 (1200 mg/kg) deleted restraint-induced NA and A increases. Both treatments also reduced the ether-induced rise of A. Basal levels of GABA were significantly increased in both the hippocampus and the hypothalamus in PC60-treated rats and only in the hippocampus in diazepam-treated ones. In controls, ether inhalation as well as restraint increased GABA content of these two brain structures. In contrast, such stress procedures performed in PC60-treated rats reduced GABA content slightly in the hippocampus but significantly in the hypothalamus. In diazepam-treated rats, GABA content of the hypothalamus was unaffected by stresses but that of the hippocampus was slightly decreased. Conclusions: Present data suggest diazepam-like effects of PC60 on stress responsiveness of the rat pituitary adrenal axis and the sympathoadrenal activity as well as GABA content of the hippocampus and the hypothalamus under resting and stress conditions. These effects of PC60 agree with anxiolytic properties of this nutritional supplement, previously reported in both rats and humans.
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  • 58
    ISSN: 1432-2072
    Keywords: Key words Morphine ; Opioid receptor ; NMDA ; Tolerance ; Rat ; Tail flick
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Pairings of a sweet taste and injection of morphine result in a learned avoidance of that taste and learned analgesic tolerance. This avoidance is mediated by the drug’s peripheral effect, while learned tolerance involves activation of N-methyl-d-aspartate (NMDA) receptors. Exposure to a sweet taste also reduces morphine analgesia. We studied whether this taste-mediated reduction was reversed by an NMDA or peripheral opioid receptor antagonist. Objectives: To determine whether an intraoral infusion of saccharin would modulate morphine analgesia in rats, and to study the contribution of NMDA as well as peripheral opioid receptors to this modulation. Methods: Six experiments used the rat’s tail-flick response to study the effect of an intraoral infusion of a sodium saccharin solution on morphine analgesia, and the effects of the quaternary opioid receptor antagonist methylnaltrexone as well as the non-competitive NMDA receptor antagonist MK-801 on this modulation of analgesia. Results: An intraoral infusion of saccharin reduced the analgesic effects of an intraperitoneal (i.p.) injection of morphine across a range of doses (experiment 1a), which was not attributable to an influence on tail-skin temperature (experiment 1b). This reduction was mediated by opioid receptors in the periphery and activation of NMDA receptors because morphine analgesia was reinstated by an i.p. injection of either methylnaltrexone (experiment 2a) or MK-801 (experiment 3a), which was not due to the effect of methylnaltrexone (experiment 2b) or MK-801 (experiment 3b) on morphine analgesia in the absence of saccharin. Conclusions: These results document evidence for an antagonism of morphine analgesia by actions of the drug at peripheral opioid receptors and excitatory amino-acid activity at NMDA receptors. They are discussed with reference to the aversive motivational effects of peripheral opioid receptors and pain facilitatory circuits.
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  • 59
    ISSN: 1432-2072
    Keywords: Key words  m-Chlorophenylpiperazine ; Drug discrimination ; Ethanol withdrawal ; Anxiety ; 17β-estradiol ; Sex difference ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The serotonergic system plays a role in regulation of anxiety and ethanol withdrawal (EW). Nevertheless, few studies have assessed sex differences in serotonergic effects on EW. Objectives: This study examined sex differences in the anxiogenic stimu-li induced by a serotonin (5-HT)1b/2 agonist, meta- chlorophenylpiperazine (mCPP), prior to ethanol and during EW. Methods: Gonadectomized or sham-operated adult male and female rats and 17β-estradiol (2.5 mg, 21-day release, s.c.) -replaced ovariectomized (OVX) rats were trained to discriminate mCPP (1.2 mg/kg, i.p.) from saline in a two-lever choice task for food. Latency to the first lever press and mCPP lever selection were measured following mCPP (0–1.2 mg/kg). Rats then received chronic ethanol-containing liquid diet (6.5%) for 10 days and were tested for mCPP lever selection 12 h and 36 h after removal of ethanol. Results: Fewer sham female and β-estradiol-replaced OVX rats selected the mCPP lever than male or OVX rats, and showed an increased initiation latency after mCPP injection. During EW (12 h and 36 h), fewer sham female and β-estradiol-replaced OVX rats responded on the mCPP-lever after saline injection as well as after mCPP challenge than male or OVX rats. Castration did not alter any response of male rats to mCPP. Conclusions: (1) mCPP discrimination is a useful measure of EW in male and female rats; and (2) sham female and β-estradiol-replaced OVX rats are less sensitive to the discriminative stimulus prior to and during EW, but more sensitive to impaired behavioral initiation induced by mCPP than male or OVX rats.
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  • 60
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    Psychopharmacology 149 (2000), S. 181-188 
    ISSN: 1432-2072
    Keywords: Key words Acoustic startle response ; Prepulse inhibition ; Sensorimotor gating ; Schizophrenia ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Prepulse inhibition of acoustic startle is the reduction in startle response to an intense auditory stimulus when this stimulus is immediately preceded by a weaker prestimulus. Prepulse inhibition occurs normally in humans and experimental animals, but schizophrenic persons often exhibit a marked impairment in this measure. Previous studies have shown that dopamine (DA)-dependent neuronal mechanisms are involved in the modulation of prepulse inhibition. Objective: Experiments were conducted in rats to elucidate further the involvement of DA-ergic mechanisms in prepulse inhibition. Results: In line with previous studies, the indirect DA agonist, amphetamine, was shown to decrease prepulse inhibition. A close reverse relationship over time between DA overflow in the nucleus accumbens and prepulse inhibition was obtained using a technique allowing concomitant measurement of these parameters in awake, freely moving rats. This effect was more pronounced in amphetamine-treated rats compared to rats treated with equimolar doses of cocaine, which increased DA overflow without affecting prepulse inhibition. In other experiments, the combined treatment with subthreshold doses of the selective DA D1 agonist, SKF 38393, and the selective DA D2 agonist, quinpirole, was also shown to decrease prepulse inhibition. Finally, the selective DA D2 antagonist, raclopride, was shown to enhance prepulse inhibition. Conclusions: In line with previous studies, it is concluded that DA neurotransmission is involved in the modulation of prepulse inhibition and that the ventral part of the mesostriatal DA system may serve an important role in this modulation. Furthermore, the possibility is discussed that the discrepant results on prepulse inhibition obtained with amphetamine and cocaine may disclose functionally relevant differences in their mechanisms of action, and that the enhancement of prepulse inhibition induced by some antipsychotics in rats may reflect their propensity to induce adverse mental effects in humans.
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  • 61
    ISSN: 1432-2072
    Keywords: Key words 8-OH-DPAT ; WAY 100635 ; 5 ; 7-Dihydroxytryptamine ; Attention ; Impulsivity ; Pre- and postsynaptic 5-HT1A receptor ; Dorsal raphe ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Whilst several studies have investigated the role of serotonergic receptor subtypes in learning and memory, relatively few studies have examined their role in attentional processes. Objective: The present study investigated the role of pre- and postsynaptic 5-HT1A receptors on rats’ attentional performance in the five-choice serial reaction time task (5-CSRT). Methods: Hungry rats were trained in the 5-CSRT task to detect brief (0.5 s) flashes of light presented randomly in one of five locations with a fixed intertrial interval of 5 s paced by the rat. We studied the effects of 8-OH-DPAT, a 5-HT1A receptor agonist, at various subcutaneous (SC) doses (10–100 µg/kg) on measures of rats’ discriminative accuracy (the index of attentional functioning) and various behavioural indices of response control and motivation. Manipulations of basic task parameters, intracerebroventricular (ICV) injections of 5,7-dihydroxytryptamine (5,7-DHT) to deplete forebrain 5-HT and treatments with a selective 5-HT1A receptor antagonist WAY 100635 were made in order to determine the behavioural and neural specificity of the effects of 8-OH-DPAT. Results: A dose of 100 µg/kg, but not lower doses, significantly reduced choice accuracy and increased errors of omission, latencies to respond correctly and to collect food reward and premature responses. All these effects were completely blocked by WAY 100635, injected SC 5 min before 8-OH-DPAT at doses from 10–100 µg/kg. WAY 100635 by itself had no effect in the task. Dimming the visual stimuli to one-third of the usual brightness did not modify the effect of 8-OH-DPAT on choice accuracy. Prolonging the stimuli from 0.5 to 1.0 s reversed 8-OH-DPAT’s effect on choice accuracy but did not modify the other effects on rats’ performance. An ICV injection of 150 µg 5,7-DHT, which depleted forebrain serotonin by 90%, reversed 8-OH-DPAT’s effect on choice accuracy but did not modify the effects on errors of omission and latency to make correct responses. Similar effects were found by infusing 1.0 µg/0.5 µl WAY 100635 in the dorsal raphe 5 min before 8-OH-DPAT. 8-OH-DPAT increased the latency to collect the reinforcement; this effect was attenuated by ICV 5,7-DHT and completely antagonized by WAY 100635 in the dorsal raphe. Rats treated with 5,7-DHT or 8-OH-DPAT showed more premature responses and these effects were markedly reduced by the combined treatment. Conclusions: The results suggest that stimulation of presynaptic 5-HT1A receptors is involved in the ability of 8-OH-DPAT to cause attentional dysfunction and enhance impulsivity while slowing of responding and increase in errors of omission mainly depend on stimulation of postsynaptic 5-HT1A receptors.
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  • 62
    ISSN: 1432-2072
    Keywords: Key words Prefrontal cortex ; Dopamine ; Anxiety ; Drug discrimination ; Pentylenetetrazol ; Chlordiazepoxide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The prefrontal cortical (PFC) dopamine (DA) system has been implicated in anxiety-related behavioral changes, but direct, unequivocal support for this idea is sparse. Objectives: The present aim was to study the functional significance of prefrontal DA using the pentylenetetrazol (PTZ) discrimination model of anxiety. A comparison was made with its role in the cue of the anxiolytic drug chlordiazepoxide (CDP). Methods: Two groups of rats were trained to discriminate either PTZ (20 mg/kg, s.c.) or CDP (10 mg/kg, i.p.) from saline using an operant drug discrimination procedure. After prolonged training, half of each group was used to assess biochemical changes induced by both drugs in different sub areas of the PFC. For the remaining rats, discrimination training continued and generalization tests with PTZ and CDP were performed. Rats were then provided with bilateral guide cannulae aimed at the ventromedial (vm) PFC, and the effects of local infusions of DAergic drugs on discriminative performance were evaluated. Results: CDP did not affect PFC DA activity, but PTZ increased the DOPAC/DA ratio in the vmPFC selectively. Generalization tests showed that the cues of PTZ and CDP were dose dependent. In PTZ-trained rats, infusions of the DA receptor antagonist cis-flupenthixol into the vmPFC blocked the PTZ cue dose dependently, whereas the agonist apomorphine partially generalized to this cue. In CDP-trained rats, neither drug antagonized or generalized to the CDP cue, showing that PFC DA is not critically involved in the CDP cue and that local pharmacological manipulations of PFC DA do not affect discriminative abilities per se. Conclusions: The DAergic innervation of the PFC is directly involved in the behavioral effects of PTZ, suggesting a role for it in anxiety.
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  • 63
    ISSN: 1432-2072
    Keywords: Key words 5-HT1A agonist ; Intrinsic activity ; Efficacy ; Irreversible antagonism ; Lower-lip retraction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Maximal responses are often used as a measure of intrinsic activity or efficacy, but cannot be directly equated to efficacy. Using irreversible antagonists, estimates of efficacy can be obtained that may be less dependent on specific conditions. Objectives: To characterize the intrinsic activity of serotonin (5-HT)1A agonists by examining the effects of an irreversible antagonist on their ability to produce 5-HT1A receptor-mediated responses. Methods: The effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on the ability of 5-HT1A agonists to produce lower-lip retraction (LLR) in rats were studied. Results: In the absence of EEDQ, each 5-HT1A agonist produced full effects, the rank order of potency being: S 14506 〉 8-OH-DPAT 〉 buspirone 〉 ipsapirone. EEDQ decreased the number of 5-HT1A binding sites and shifted the dose–response curves (DRCs) of each agonist either to the right or, at higher EEDQ doses, to the right and downward. The manner in which these shifts occurred, however, differed among the compounds. For each agonist, all DRCs obtained after different doses of EEDQ were fitted to models proposed by Furchgott and Black and Leff, and the results indicated the following rank order of efficacy: ipsapirone 〈 buspirone ≈ 8-OH-DPAT 〈 S 14506. 5-HT1A agonist-induced LLR appears to be mediated by 5-HT1A receptors, because the 5-HT1A antagonist, WAY 100635, shifted the agonist DRCs to the right in a parallel and dose-related manner, with pA2 values ranging from 7.8 to 8.1. Moreover, pretreatment with WAY 100635 protected against the antagonist activity of EEDQ. Conclusions: The results suggest that the effects of EEDQ on the ability of 5-HT1A agonists to produce LLR in rats may be useful to obtain estimates of their apparent efficacy at 5-HT1A receptors.
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  • 64
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    Psychopharmacology 148 (2000), S. 106-110 
    ISSN: 1432-2072
    Keywords: Key words Interferon ; Depression ; Forced swimming test ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objectives: We examined the immobility of the forced swimming test induced in an animal model by human interferon (IFN), which has often been reported to induce depression in clinical use. Methods: In the present study, we examined the effects of human IFNs on results of the forced swimming test in rats. Results: Single intravenous (IV) administration of human IFN-α (6×104 IU/kg), but not of human IFN-β or -γ, significantly increased immobility time in the forced swimming test in rats. Repeated administration of human IFN-α (6×103 IU/kg) also significantly increased the immobility time. On the other hand, none of the rat IFNs (rat IFN-α, -β and -γ, 6×104 IU/kg, IV) changed the immobility time. Neither human IFNs nor rat IFNs changed the locomotor activity of rats. Conclusions: These findings suggest that human IFN-α has a greater potential for inducing increase of the immobility in the rat forced swimming test than human IFN-β and -γ, and that the effect of human IFN-α might not be mediated through IFN-α/β receptors.
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  • 65
    ISSN: 1432-2072
    Keywords: Key words Opiate receptor ; Antinociception ; Habituation ; Novelty ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: There is now extensive evidence demonstrating that exposure to novel stimuli induces hypoalgesia and that this effect habituates over repeated exposure to the stimuli. Moreover, it has been shown that administration of the nonselective opiate receptor antagonist naloxone can attenuate the rate of habituation of novelty-induced hypoalgesia. Objectives: The present experiments were conducted to determine the relative influence of different opiate receptor subtypes in the attenuation of the habituation of novelty-induced hypoalgesia. Methods: In experiments 1–3, different groups of male, Wistar rats (275–300 g) were administered vehicle, 0.5, 1.0 or 2.0-nmol doses of the µ-selective antagonist Cys2-Tyr3-Orn5-Pen7-amide (CTOP), the δ-receptor selective antagonist naltrindole, or the κ-selective antagonist nor-binaltorphimine (nor-BNI). In experiment 4, animals were administered vehicle, 5, 25 or 75-nmol doses of nor-BNI. All injections were delivered to the right lateral ventricle 30 min prior to exposure to a novel hot-plate apparatus (48.5°C), once a day for eight consecutive days. Results: Paw-lick latencies in vehicle-treated animals were long during the initial exposures and declined over repeated tests, suggesting the habituation of novelty-induced hypoalgesia. The rate of habituation was significantly attenuated by administration of 1.0-nmol and 2.0-nmol doses of CTOP, by a 2.0-nmol dose of naltrindole, but was unaffected by all doses of nor-BNI. Conclusions: These results support the involvement of the µ and δ, but not the κ, opiate receptor subtypes in the habituation of novelty-induced hypoalgesia.
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  • 66
    ISSN: 1432-2072
    Keywords: Key words Fentanyl ; mu opioids ; Drug discrimination ; Training dose ; pA2 analysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Discriminative stimulus effects of mu opioids vary systematically as a function of training dose. Differences among training doses may arise from multiple mechanisms. Objectives: In vivo apparent pA2 analyses were used to examine the contributions of opioid mechanisms to stimulus control by low and high training doses of the mu opioid fentanyl. Methods: Saline and one of two doses of fentanyl, administered s.c., were established as discriminative stimuli in two groups of rats (low training dose group: 0.01 mg/kg; high training dose group: 0.04 mg/kg). Generalization tests and in vivo apparent pA2 analyses were used to evaluate receptor mechanisms of stimulus control. Results: Fentanyl, etonitazene, methadone, and morphine evoked full fentanyl generalization in both groups but were more potent in the low-dose group. Spiradoline and d-amphetamine did not evoke generalization in either group. Naltrexone antagonized stimulus and rate-altering effects of fentanyl in both groups, with apparent pA2 values of 7.6 in the low-dose group and 7.5 in the high-dose group. Nalbuphine and nalorphine evoked full generalization in the low-dose group but less than 40% generalization in the high-dose group. In the high-dose group, nalbuphine and nalorphine antagonized the stimulus and rate-altering effects of fentanyl with apparent pA2 values of 5.3 and 6.1, respectively, demonstrating lower efficacy mu actions. Conclusions: Changes in fentanyl training dose preserved the mu opioid selectivity of stimulus control but altered the intensity of the transduced mu opioid stimulus required for generalization. These differences in intensity of the fentanyl stimulus determined whether low efficacy mu opioids would evoke or antagonize fentanyl generalization.
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  • 67
    ISSN: 1432-2072
    Keywords: Key words Benzodiazepine ; Operant ; Force ; Tolerance ; Chronic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Several benzodiazepines (BZs) have been shown to increase the peak force of operant responses at doses that increased, decreased, or had no effect on response rate, suggesting that operant response force may be a sensitive index of BZs’ effects rather than solely a correlate of rate-dependent effects. In addition, contingent tolerance to the rate-dependent effects of BZs has been reported, but the degree of contingent tolerance that develops when the critical variable of the task is force of the response has not been explored. Objectives: These experiments examined the effects of acute and repeated oral administration of diazepam (DZ) and midazolam (MZ) on a force-differentiation task to explore the importance of task requirements on the development of contingent tolerance. Methods: Two groups of rats were trained to press a force-sensing operandum, and responses having peak forces falling within fixed lower and upper limits [low force (8–10 g) or high force (40–50 g)] were reinforced with water. Acute effects of the oral administration of DZ (0.3, 1.0, 3.0, 10.0, 30.0 mg/kg) and MZ (same doses) were determined for the discriminated-force task before and after a repeated-administration procedure. Results: When administered acutely, both drugs increased the peak force of responses in a dose-related manner and concomitantly reduced the proportion of reinforced responses, with MZ exhibiting greater potency. For the next 36 days, one group received drug before experimental sessions and the other group received drug after the experimental session. A second dose–effect determination demonstrated that rats chronically dosed with DZ or MZ pre-session displayed more contingent tolerance to alterations in peak force than rats that had received 36 drug injections post- session, where there was no opportunity to practice the force-discrimination response while under the drug state. Conclusions: These results suggest that perceptual motor difficulty of the task rather than effort may be an important variable in predicting the degree of contingent tolerance that develops. Additionally, these results suggest that both behavioral and pharmacological mechanisms are involved in the development of drug tolerance to the BZs.
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  • 68
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    Psychopharmacology 148 (2000), S. 146-152 
    ISSN: 1432-2072
    Keywords: Key words Alprazolam ; Drug discrimination ; Benzodiazepines ; Antidepressant ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The triazolobenzodiazepine alprazolam has a unique clinical profile compared to most other benzodiazepines (e.g. diazepam, chlordiazepoxide), in that it is used to treat panic disorder and is effective in depression, two disorders that are usually treated with anti-depressants. Previous drug discrimination studies suggested that alprazolam has stimulus properties in common with antidepressants. Objective: In the present study, the discriminative stimulus properties of alprazolam were investigated to test more conclusively the role of benzodiazepine receptors and whether alprazolam has stimulus properties in common with antidepressants. Methods: Male Wistar rats (n=12) were trained to discriminate between alprazolam (2.0 mg/kg, PO) and vehicle in an operant two-lever drug discrimination procedure under a tandem VI40”-FR10 schedule of reinforcement. Generalization and antagonism tests were carried out under 2 min extinction. Results: In generalization tests, a number of benzodiazepines (alprazolam, chlordiazepoxide, midazolam, lorazepam) and the barbiturate pentobarbital substituted completely, while zolpidem and abecarnil substituted partially for alprazolam. In contrast, no significant degree of generalization to the antidepressants imipramine and fluvoxamine and the putative antidepressants buspirone and flesinoxan was found. In antagonism studies alprazolam could be antagonized (almost) completely by flumazenil, partially by pentylenetetrazole, but not by methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), N-methyl-β-carboline-3-carboxamide (FG-7142) and picrotoxin. Conclusions: These results show that the discriminative stimulus properties of alprazolam are mediated by benzodiazepine receptors and that the finding that antidepressants share discriminative stimulus effects with alprazolam may have limited generality.
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  • 69
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    Psychopharmacology 148 (2000), S. 209-216 
    ISSN: 1432-2072
    Keywords: Key words Methamphetamine ; Drug-discrimination ; Dopamine ; Cocaine ; GBR-12909 ; Nomifensine ; Bupropion ; Chloro-PB ; Chloro-APB ; NPA ; 7-OH-DPAT ; SCH-23390 ; Spiperone ; cis-Flupenthixol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Dopamine plays a major role in the behavioral effects of methamphetamine. Objective: In the present experiments, the effects of different dopaminergic agonists, antagonists, and uptake inhibitors were evaluated in rats discriminating methamphetamine from saline. Methods: In Sprague-Dawley rats trained to discriminate 1.0 mg/kg methamphetamine, i.p., from saline under a fixed-ratio schedule of food delivery, the ability of various dopaminergic agonists and uptake inhibitors to substitute for methamphetamine was evaluated. Subsequently, the ability of various dopaminergic antagonists to block the discriminative-stimulus effects of the training dose of methamphetamine was tested. Results: The dopamine-uptake inhibitors cocaine (10.0 mg/kg), nomifensine (3.0 mg/kg), GBR-12909 (18.0 mg/kg), and bupropion (30.0 mg/kg) fully substituted for the 1.0 mg/kg training dose of methamphetamine. Chloro-APB (SKF-82958), a full agonist at D1 dopamine receptors, produced about 85% methamphetamine-appropriate responding, but the dose required (0.18 mg/kg) markedly decreased rates of responding. Chloro-PB (SKF-81297), another agonist at D1 receptors with a lower intrinsic activity than Chloro-APB, produced only partial generalization (maximum about 55%) at a dose of 1.0 mg/kg. Full substitution for the training dose of methamphetamine was observed with 0.03 mg/kg of the D2 agonist NPA and 0.56 mg/kg of the D3/D2 agonist 7-OH-DPAT. Both NPA and 7-OH-DPAT markedly decreased rates of responding at these doses. The D1 antagonist SCH-23390 (0.056 mg/kg), the D2 antagonist spiperone (0.18 mg/kg), and the mixed D1,D2 antagonist cis-flupenthixol (0.56 mg/kg) all completely blocked the discriminative-stimulus actions of the training dose of methamphetamine. Conclusions: The present findings in rats support previous research findings in other species indicating a major role of dopamine in the discriminative-stimulus effects of methamphetamine. These findings further indicate involvement of dopamine uptake sites as well as D1 and D2 receptors.
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  • 70
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    Psychopharmacology 149 (2000), S. 115-120 
    ISSN: 1432-2072
    Keywords: Key words Opiate ; Withdrawal ; Place aversion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Administration of low doses of opiate antagonists to morphine-dependent rats produces an aversive response as measured by a conditioned place aversion, but the time course of such a learned aversion is largely unknown. Objectives: The purpose of this experiment was to examine the time course for the expression of a place aversion to opiate withdrawal. Methods: Morphine-dependent rats were tested in a three-chamber place- aversion apparatus. The conditioning phase consisted of three pairings of either naloxone (15 µg/kg s.c.) or vehicle with two compartments, with the most similar time allotments during the preconditioning test. During the testing phase, rats were again allowed to explore the entire apparatus. Different groups were tested at 24 h, 1 week, 2 weeks, 4 weeks, 8 weeks, and 16 weeks post-conditioning (morphine-free tests). Results: A robust place aversion was recorded at every time point tested, including at 16 weeks. In previously published work, placebo-pelleted rats tested with naloxone at the same dose failed to show a place aversion and nondependent rats showed a stable lack of aversion at tests up to 56 days. Dependent animals without naloxone also failed to show a place aversion at any of those time points. Conclusions: In the absence of any active intervention, the place aversion produced by opiate withdrawal is very long lasting and provides a model for protracted abstinence that may be useful for delineating the neurobiological substrate for vulnerability to relapse.
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  • 71
    ISSN: 1468-2869
    Keywords: Asthma ; Children ; Chronic illnesses ; Diabetes ; Self-help ; Training
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Abstract A randomized field trial of a child-centered model of training for self-management of chronic illnesses was conducted of 355 Spanish-speaking school-aged children, between 6 and 15 years old, with moderate to severe asthma and epilepsy, in Buenos Aires, Argentina. The model, based on play techniques, consists of five weekly meetings of 8–10 families, with children's and parents' groups held simultaneously, coordinated by specially trained teachers and outside the hospital environment. Children are trained to assume a leading role in the management of their health; parents learn to be facilitators; and physicians provide guidance, acting as counselors. Group activities include games, drawings, stories, videos, and role-playing. Children and parents were interviewed at home before the program and 6 and 12 months after the program, and medical and school records were monitored for emergency and routine visits, hospitalizations, and school absenteeism. In asthma and epilepsy, children in the experiment showed significant improvements in knowledge, beliefs, attitudes, and behaviors compared to controls (probability of experimental gain over controls=.69 for epilepsy and .56 for asthma, with σ2= .007 and .016, respectively). Parent participants in the experiment had improved knowledge of asthma (39% before vs. 58% after) and epilepsy (22% before vs. 56% after), with a probability of gain=.62 (σ2=.0026) with respect to the control group. Similar positive outcomes were found in fears of child death (experimental 39% before vs. 4% after for asthma, 69% before vs. 30% after for epilepsy), as well as in disruption of family life and patient-physician relationship, while controls showed no change. Regarding clinical variables, for both asthma and epilepsy, children in the experimental group had significantly fewer crises than the controls after the groups (P=.036 andP=.026). Visits to physicians showed a significant decrease for those with asthma (P=.048), and emergency visits decreased for those with epilepsy (P=.046). An 18-item Children Health Locus of Control Scale (CHLCS) showed a significant increase in internality in experimental group children with asthma and epilepsy (P〈.01), while controls did not change or performed worse 12 months after the program. School absenteeism was reduced significantly for those with asthma and epilepsy (for the group with asthma, fall/winterP=.006, and springP=.029; for the group with epilepsy,P=.011). Conclusion The program was successful in improving the health, activity, and quality of life of children with asthma and epilepsy. The data suggested that an autonomous (Piagetian) model of training is a key to this success, reinforcing children's autonomous decision making.
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  • 72
    ISSN: 1438-8359
    Keywords: Key words: Halothane ; Dopamine release ; Dopamine uptake ; Microdialysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose. In our previous microdialysis study, sevoflurane or isoflurane anesthesia significantly decreased the extracellular level of dopamine in rat striatum in vivo. On the other hand, other investigators demonstrated that halothane anesthesia either increased or did not affect the extracellular dopamine level. To explore the differences among these volatile anesthetics, the effects of halothane and nitrous oxide on the striatal dopamine level were reinvestigated. Methods. Halothane alone, nitrous oxide with or without halothane, or drugs known to affect the dopaminergic pathway were administered to rats. Microdialysates were collected every 20 min and directly applied to an on-line high-performance liquid chromatograph without any pretreatment. The effects of halothane on respiratory and cardiovascular variables were monitored. Results. General anesthesia with halothane alone de-creased the dialysate (extracellular) concentration of dopamine but increased that of dopamine metabolites. Nitrous oxide alone slightly increased dopamine metabolites in dialysates but did not affect the halothane-induced decrease in extracellular dopamine. Apomorphine and haloperidol reproduced reported results, confirming the adequacy of our methodology. Nomifensine- or methamphetamine-induced increase in extracellular dopamine was augmented by halothane. Conclusion. These results suggest that halothane po-tently enhances striatal dopamine release and activates the reuptake or metabolic process, which is consistent with our previous results for sevoflurane or isoflurane. Volatile anesthetics interfere with dopamine regulation, at least in the rat striatum.
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  • 73
    ISSN: 1436-2023
    Keywords: Key words Adriamycin ; Rat ; Embryo ; VATER association ; Synovial joint ; Bones ; Limbs ; Vertebra ; Sirenomelia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The adriamycin-induced rat model of the Vertebral, Anorectal, Tracheo-Esophageal, Radial and Renal (VATER) association produces a variety of vertebral, rib, and limb abnormalities. This study was designed to document accurately the nature of these abnormalities and to determine whether synovial joints are affected. Fetuses from pregnant Sprague Dawley rats that had received intraperitoneal injections of 1.75 mg/kg of adriamycin on days 6–9 or 10–13 of gestation were harvested. Double-stained skeletal preparations and histological sections were examined for vertebral, rib, and limb anomalies. The incidence of anomalies was high in the group treated on gestational days (GD) 6–9, while it was low in the GD 10–13 group. The length and thickness of the long bones were reduced, with bowing and reduction in their endochondral ossification. Sirenomelia occurred in the group treated on GD 6–9, and was often associated with a short tail and anal atresia. The joint cavities, and intra-articular structures such as menisci and the cruciate ligaments developed normally from the mesenchymal interzone. These data indicate that adriamycin inhibits skeletal growth and differentiation without any interference in the differentiation of the mesenchymal interzone, thus producing normal synovial joints.
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  • 74
    ISSN: 1530-0358
    Keywords: Pravastatin ; ras p21 isoprenylation ; Colon carcinogenesis ; Flat colon tumor ; Azoxymethane ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The effect of pravastatin, an inhibitor ofras p21 isoprenylation, on the gross type of colon tumors induced by azoxymethane was investigated in Wistar rats. METHODS: Rats received ten weekly subcutaneous injections of 7.4 mg/kg body weight of azoxymethane and intraperitoneal injections of 10 or 20 mg/kg body weight of pravastatin every other day until the end of the experiment at Week 45. RESULTS: Administration of pravastatin at both dosages had no significant effect on the incidence of colon tumors but significantly increased the incidence of rats with adenomas only. In contrast to the elevated adenomas in control rats, flat adenomas were significantly more prevalent in rats given pravastatin. Pravastatin at both doses significantly decreased the labeling index, but not the apoptotic index, of elevated adenomas, whereas it significantly decreased the labeling index but increased the apoptotic index of flat adenomas. Administration of pravastatin at both dosages also significantly decreased the amounts of membrane-associatedras p21 in colon tumors. CONCLUSIONS: These findings suggest that theras oncogene may be closely related to the development of adenocarcinomas from adenomas and the development of elevated or polypoid tumors of the colon.
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  • 75
    ISSN: 1436-3771
    Keywords: Key words Age ; Children ; Dental fluorosis ; Severity ; Tooth eruption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose of this study was to investigate the influence of age on the severity of dental fluorosis in children exposed to drinking water with either low or high fluoride concentrations. The children selected for this study were aged 10–14 years, with 28 permanent teeth and at least 1 tooth pair with fluorosis. The children were permanent residents of districts in western Uganda with either 0.5 mg (n=33) or 2.5 mg fluoride/l in drinking water (n=186). All vestibular tooth surfaces were examined for fluorosis using the modified Thylstrup and Fejerskov (TF) index. In the high fluoride community, the proportion of teeth per child with TF scores ≥4, and ≥5 was significantly higher among children aged 13–14 years compared to those aged 10–12 years. Children’s chronological age correlated positively and significantly with the median TF scores for all teeth, including early erupting (first molars and incisors) and late erupting teeth (canines, premolars and second molars). In linear regression analyses, the median TF score for all teeth, as well as for early erupting and late erupting teeth, increased significantly with age. On the other hand, in the low fluoride community there was no significant association between age and the severity of fluorosis. This study showed a significant increase in the severity of fluorosis with increasing age in a high fluoride community, whereas no change in severity with age was observed in a low fluoride community.
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  • 76
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    Trauma und Berufskrankheit 2 (2000), S. S138 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Vorderes Kreuzband ; Kind ; Wachstumsfuge ; Fehlwachstum ; Key words ; Anterior cruciate ligament ; Children ; Growth plate ; Growth disturbance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Lesions of the anterior and posterior cruciate ligaments are relatively rare in childhood and adolescence; in this age group they need even more consistent and aggressive treatment than in adults as far as conservation of the menisci and definitive stabilization are concerned. Virtually no cases in which serious growth disturbance has arisen following transepiphyseal drilling are known from the literature. Thus, cruciate ligament suturing should also not be done in children, because the long-term efficacy has not been confirmed. The operative procedure is presented in detail and is related to bone age. Early transepiphyseal drilling is permissible.
    Notes: Zusammenfassung Ligamentäre Kreuzbandverletzung beim Kind und im Adoleszentenalter sind relativ selten, sie bedürfen im Vergleich zum Erwachsenen ¶einer noch konsequenteren und aggressiven Behandlung bezüglich Meniskuserhalt und definitiver Stabilisierung. In der Literatur sind praktisch keine Fälle bekannt, bei denen es tatsächlich zu einem gravierenden Fehlwachstum nach transepiphysärer Bohrung gekommen ist. Insofern sollte auch die Kreuzbandnaht beim Kind wegen der nicht bewiesenen Langzeiteffizienz unterlassen werden. Das Vorgehen im Einzelnen in Bezug zum Skelettalter wird dargestellt. Frühzeitige transepiphysäre Bohrungen sind erlaubt.
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  • 77
    ISSN: 1432-1211
    Keywords: Key words Vβ13 ; CD4/CD8 ratio ; Rat ; Tcrb ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Three rat BV13S1 alleles (T-cell receptor β-chain variable gene 13) were characterized by new BV13S1-allele specific monoclonal antibodies (18B1 and 17D5) and sequence analysis of expressed and genomic BV13S1. Two alleles were functional and designated BV13S1A1 present in strains LEW, BUF, PVG, and BV13S1A2 present in BN and WF. Their products differed by six amino acids, two of them in complementarity-determing region (CDR)1 and one in CDR2. A third nonfunctional allele, BV13S1A3P, was found in strains F344 and DA. Apart from a single nucleotide insertion, it was identical to BV13S1A2. All 12 rat strains tested showed association of TCRBC1 with BV8S2/4 alleles but not with the BV13S1 alleles, which may reflect a different gene order of the rat BV compared to mouse. BV13S1A1-encoded T-cell receptors (TCRs) which bind both monoclonal antibody (mAb) 18B1 and mAb 17D5 are over-represented in the CD4 lymphocyte subset. BV13S1A2-encoded TCRs which are stained by mAb 18B1 but not by mAb 17D5 show a slight CD8-biased expression. Preferential usage of BV13S1A1-positive TCRs by CD4 but not by CD8 cells in (LEW×WF)F1 hybrids and cosegregation of BV13SA1 and increased frequency of BV13S1 TCR-positive CD4 cells in a (LEW×BN)×BN backcross suggest structural differences of the two allelic products as the reason for their contrasting CD4/CD8 subset bias.
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  • 78
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; Children ; Risk factors for survival ; Primary non-function ; Hepatic artery thrombosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several recipient, donor and operation factors as well as postoperative complications related to patient survival after liver transplantation (LT) in children were studied by univariate and multivariate analyses . In a 13-year period, 103 patients under 15 years of age underwent 120 LT; the mean age was 63 months and 36 % were under 2 years of age. Indications for LT were cholestatic disease in 68 (56 %), metabolic diseases in 18 (14 %), fulminant hepatic failure in 8 (7.5 %), cirrhosis in 7 (5.8 %), and retransplants in 17 (14 %). Whole liver was transplanted in 79 % of cases and partial liver in 21 %. Actuarial survival at 1, 5, and 10 years was 70 %, 61 %, and 57 %, respectively. United Network of Organ Sharing (UNOS) I recipients (RR = 2.7), primary non-function (PNF) (RR = 13.9), and hepatic artery thombosis (HAT) (RR = 3.8) were independent factors for lower patient survival in multivariate analysis. Thus, in our experience, postoperative mortality as a consequence of the patient's condition before transplantation, or complications such as PNF or HAT, are the major causes of decreased survival in pediatric LT.
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  • 79
    ISSN: 1432-0568
    Keywords: Key words Nerve repair ; Nerve fiber regeneration ; Sciatic nerve ; Muscle-vein-combined graft ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Clinical data have shown that a vein segment filled with fresh skeletal muscle can be considered a good autologous grafting conduit for the repair of peripheral nerve lesions. In this study, the long-term morphological organization of rat sciatic nerve fibers regenerated along a muscle-vein-combined graft conduit is further analysed by light and electron microscopy. Regenerated nerve fibers were organized into fascicles of various sizes that were clearly delimited by perineurial-like shells made by long and thin cytoplasmic processes of perineurial-like bipolar cells and by densely packed collagen fibrils. Grafted skeletal muscle fibers were still detectable among nerve fiber fascicles. However, in spite of the persistence of skeletal muscle along the graft, regenerated nerve fibers showed a good morphological pattern of regeneration, providing further evidence that the muscle-vein-combined grafting technique represents an effective surgical alternative to the classical fresh nerve autograft for the repair of peripheral nerve defects.
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  • 80
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    Anatomy and embryology 202 (2000), S. 247-255 
    ISSN: 1432-0568
    Keywords: Key words Enteric neurons ; Interstitial cells of Cajal ; Smooth muscle cells ; Guinea-pig ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Tachykinin receptors NK1r, NK2r and NK3r bind tachykinins with different affinities and share pharmacological and molecular differences among animal species. NK1r, NK2r, NK3r and tachykinin (SP/NKA) distribution was studied by immunohistochemistry in the ileum of mouse since no data are available for this species. The results were then compared to those obtained in the rat and guinea pig either by us or by others to ascertain interspecies similarities and/or differences. NK1r- and NK3r-immunoreactivity (IR) were detected in neurons and NK1r-IR in the interstitial cells of Cajal at the deep muscular plexus. At variance with rat and guinea pig, NK1r-IR was also found in the myoid cells of the villi, while NK2r-IR was never detected in nerve varicosities. This latter datum suggests that the NK2r does not play a presynaptic role in the mouse. Unexpectedly, a high NK2r-IR and the presence of NK3r-IR were observed at the inner portion of the circular muscle layer in the mouse as well as in the rat and guinea pig, demonstrating a subregional distribution of these receptors. Tachykinin distribution did not show noticeable species-related differences. The present findings show species-related differences in the tachykinin receptor distribution that might be related to a different tachykinin controlof intestinal motility.
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  • 81
    ISSN: 1432-0568
    Keywords: Key words GABAB receptor ; CNS ; Dorsal root ganglia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The anatomical distribution of the GABAB receptor (GBR) splice variants GBR1a and 1b in the CNS has not previously been studied. In the present study, distribution of the splice variants was mapped using immunohistochemistry. Polyclonal antibodies against splice variant unique epitopes were raised in rabbits. Affinity purified antibodies were used according to routine immunohistochemical procedures in sections from the rat CNS or dorsal root ganglia (DRG). The staining intensity was high in the cerebral cortex but lower in basal ganglia and the hippocampus. In the cerebellum, there was a marked difference in the distribution of GBR1a- and 1b-like immunoreactivity (LI). GBR1a-LI was preferentially localised in the granule cell layer whilst GBR1b-LI was mostly found in Purkinje cells and in the molecular layer. Cell bodies of the deep cerebellar nuclei stained for the GBR1a antibody while terminals surrounding the cell bodies were strongly labelled with the GBR1b antibody. A similar pre- vs postsynaptic pattern was seen in several nuclei ventral or caudal to the cerebellum (e.g. the cochlear nucleus, the facial nucleus, the spinal cord) but not in regions rostral to the cerebellum. In the spinal cord, strong labelling for both antibodies was seen in the dorsal horn. The GBR1b but not the GBR1a antibody stained tanycytes in the epithelium of the 3rd ventricle and in the central canal at the brain stem level. DRG neurons were positive for both the GBR1a and 1b antibody, but the former stained the cells much more intensely. Satellite cells were labelled with the GBR1b antibody. The most important aspect of these findings is that in some nuclei, GBR1b may mediate inhibition of transmitter release while in the same regions, GBR1a may mediate postsynaptic inhibition. Further, the observations support previous findings that GBR1b is the predominant splice variant in Purkinje cells.
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  • 82
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    Intensive care medicine 26 (2000), S. 942-949 
    ISSN: 1432-1238
    Keywords: Key words Ventilator-associated pneumonia ; Cardiac surgery ; Children ; Pediatric intensive care ; Complications ; Extubation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: This study was undertaken to determine the delay of extubation attributable to ventilator-associated pneumonia (VAP) in comparison to other complications and complexity of surgery after repair of congenital heart lesions in neonates and children.¶Methods: Cohort study in a pediatric intensive care unit of a tertiary referral center. All patients who had cardiac operations during a 22-month period and who survived surgery were eligible (n = 272, median age 1.3 years). Primary outcome was time to successful extubation. Primary variable of interest was VAP. Surgical procedures were classified according to complexity. Cox proportional hazards models were calculated to adjust for confounding. Potential confounders comprised other known risk factors for delayed extubation.¶Results: Median time to extubation was 3 days. VAP occurred in 26 patients (9.6 %). The rate of VAP was not associated with complexity of surgery (P = 0.22), or cardiopulmonary bypass (P = 0.23). The adjusted analysis revealed as further factors associated with delayed extubation: other respiratory complications (n = 28, chylothorax, airway stenosis, diaphragm paresis), prolonged inotropic support (n = 48, 17.6 %), and the need for secondary surgery (n = 51, 18.8 %; e. g., re-operation, secondary closure of thorax). Older age promoted early extubation. The median delay of extubation attributable to VAP was 3.7 days (hazards ratio HR = 0.29, 95 % CI 0.18–0.49), exceeding the effect size of secondary surgery (HR = 0.48) and other respiratory complications (HR = 0.50).¶Conclusion: VAP accounts for a major delay of extubation in pediatric cardiac surgery.
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  • 83
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    Trauma und Berufskrankheit 2 (2000), S. S136 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Vordere Kreuzbandverletzung ; Kinder ; Rekonstruktion ; Indikation ; Key words ; ACL lesion ; Children ; Reconstruction ; Indications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract For ACL lesions in children near to the end of the growth phase the treatment can be treated identical to that in adults. For younger children (8–12 years) the treatment must be conservative, combined with controls at short intervals. Behaviour during sport should be modified. If instability is experienced in activities of daily life or during sport a reconstruction of the ACL should be done using a central tibial transepiphyseal hamstring reconstruction with a femoral over-the-top position to avoid possible growth disturbances.
    Notes: Zusammenfassung Kreuzbandverletzungen bei Kindern, die nahe ihres Wachstumsabschlusses sind (14. bis 17. Lebensjahr) können wie Kreuzbandverletzungen von Erwachsenen behandelt werden. Kreuzbandverletzungen bei Kindern, die 13 Jahre und jünger sind, sollten zunächst abwartend behandelt werden (Kniebandage, Koordinationstraining, Belastungsreduzierung). Stellt sich im täglichen Leben oder bei sportlicher Belastung eine Instabilität im Sinne eines Giving way heraus, so sollte das Kreuzband rekonstruiert werden. Dabei ist es nach allen vorliegenden Daten unbedenklich, die Tibia zentral mit einem 8-mm-Bohrloch zu durchbohren und ein ligamentäres Transplantat durchzuziehen. Femoral ist es aus Sicherheitsgründen eher sinnvoll, statt einer transossären Bohrung die Over-the-top-Position zu wählen. Auch andere, rein epiphysäre Verankerungsmethoden (Semitendinosusplastik mit transossärer Drahtfixation) sind möglich.
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  • 84
    ISSN: 1439-0973
    Keywords: Key Words Ritonavir ; Nelfinavir ; Children ; Antiretroviral agents ; HIV-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Background: Knowledge concerning the long-term antiretriviral and immunological efficacy of protease inhibitors in children is limited. Patients and Methods: An open-label, prospective, multicenter clinical trial was conducted over a period of 72 weeks in Switzerland. 60 HIV-1 infected children (aged 0.3–16.9 years) naive to protease inhibitors were enrolled. Ritonavir or nelfinavir and at least one new nucleoside reverse transcriptase inhibitor were introduced into the durrent treatment regimen. HIV-1 RNA levels and CD4 cell counts were monitored after introducing the protease inhibitor, and the tolerability and safety of the drugs were assessed. Results: Dictated by chronological availability, 37 children received ritonavir and 23 nelfinavir. At baseline, children given ritonavir had higher mean plasma HIV-1 RNA levels (5.03 vs 4.63 log10 copies/ml; p = 0.001) and lower mean CD4 cell counts (277 vs 555 cells/μl; p = 0.009) than children given nelfinavir. Antiretroviral treatment (ART) naive children showed higher mean plasma HIV-1 RNA levels than non-naive (5.18 vs 4.64 log10 copies/ml; p = 0.02). The decline in plasma HIV-1 RNA levels 72 weeks after treatment with ritonavir and nelfinavir was −2.17 and −1.30 log10 copies/ml, respectively (p = 0.006) and in ART-naive vs non-naive patietns −2.70 vs − 1.39 log10 copies/ml (p ≤ 0.01). 69% of ART-naive patients and 32% of non-naive patients achieved sustained plasma HIV-1 RNA levels 〈 400 copies/ml. Increases in CD4 cells were higher in ART naive compared to non-naive patients (p 〈 0.04). Conclusion: The antiretroviral and immunologic benefits of protease inhibitors are more profound in ART-naive than in non-naive children.
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  • 85
    ISSN: 1439-0973
    Keywords: Key words Tick-borne encephalitis ; Children ; Adults
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this prospective study was to compare epidemiological data and clinical features in children and adults with tick-borne encephalitis (TBE). Patients with aseptic meningitis diagnosed at the University Medical Centre, Department of Infectious Diseases, Ljubljana, Slovenia, from June to August 1997, in whom the diagnosis of TBE was ascertained by the presence of serum IgM antibodies against TBE virus, who were serologically negative for Borrelia burgdorferi sensu lato and had a negative PCR CSF result on enteroviral infection, were included in the study. Out of 213 patients with aseptic meningitis, 80 (37–56%) fulfilled inclusion criteria. There were 20 children and 60 adults. In both groups males predominated. Virtually all patients had headache and fever, and more than 50% suffered from vomiting. The majority of patients in both groups recalled a tick bite, had a biphasic course of the illness, and was found to have obviously expressed meningeal signs. In both groups the median CSF leukocyte count was somewhat lower than 100 × 106/l with a predominance of lymphocytes. Children were more often given antibiotics during the initial phase of TBE than adults (p = 0.0095). Several other statistically significant distinctions (p 〈 0.05) were found including the frequency of fatigue, malaise, vertigo, photophobia, myalgias, arthralgias, as well as elevated CSF albumin and protein concentration, elevated albumin quotient and IgG quotients; all these findings were more often present in adults. In addition a longer duration of fever, more frequent need for anti-edematous treatment and longer hospitalization were found in adults. Direct comparison of clinical and epidemiological characteristics of TBE in children and adults revealed differences in several clinical and laboratory features and corroborates the previous conclusion that TBE in childhood is a milder illness than TBE in adults.
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  • 86
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    Journal of urban health 77 (2000), S. 723-734 
    ISSN: 1468-2869
    Keywords: Child welfare ; Children ; Disclosure ; HIV ; Mothers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this investigation was to ascertain the reasons given by mothers diagnosed with AIDS (acquired immunodeficiency syndrome) for disclosing or not disclosing their HIV (human immunodeficiency virus) status to their children, a dilemma faced by most HIV-infected parents and those who counsel them. We interviewed 29 mothers residing in one of two New York City facilities that provide housing and medical treatment for adults with AIDS. The majority of these mothers do not live with their children, but all had recent face-to-face contact with them. The two reasons most frequently considered important for disclosing to children were that disclosure was the “right thing to do” and the need to make arrangements for children's future in case of maternal death or incapacity. The reason most frequently considered important for not disclosing was maternal concern about discussing death and dying with children. These findings have significant implications for counseling of HIV-positive parents.
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  • 87
    ISSN: 1439-0973
    Keywords: Key words Pertussis ; Bordetella pertussis ; Hospitalization ; Complications ; Vaccine ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We prospectively followed 725 children under 2 years of age with laboratory-diagnosed Bordetella pertussis infection to investigate the hospitalization rate and complications. Diagnosis was made by culture and polymerase chain reaction (PCR) from nasopharyngeal swabs in 11,016 children who presented with ≥ 7 days of cough at 63 pediatric practices in Germany. Of these children, 33 (4.5%) were hospitalized at a mean age of 4.8 months (range, 17 days to 19.5 months). Complications occurred in 16 (48%) of the 33 patients. Pneumonia developed in two (6%) children and a convulsion was observed in one (3%). Intensive care monitoring was required for 23 (70%) children. Further complications were bradycardia (21%), apnea (12%), conjunctivitis (12%), loss of weight (12%), otitis media (6%), atelectasis (3%) and dehydration (3%). Children aged 6–24 months who had not received any dose of pertussis vaccine had a ten-fold increased risk of hospitalization compared to those who had been partially or fully immunized (p 〈 0.05). Pertussis immunization should be given at an early point in time and completely in order to prevent severe courses of pertussis and hospitalization in young children.
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  • 88
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    Infection 28 (2000), S. 282-286 
    ISSN: 1439-0973
    Keywords: Key Words Chronic ; Osteomyelitis ; Therapy ; Children ; Ewing's sarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Background: Presently, most children with chronic osteomyelitis undergo surgery with the inherent risk of damage to their growth plate. We demonstrate a treatment regimen based on imaging procedures focussing on antibiotics in order to reduce the rate of surgical interventions. Patients and Methods: We retrospectively evaluated all 11 patients with clinically suspected chronic osteomyelitis who were treated at our institution from 1989 to 1995. Patients underwent open biopsy and surgical treatment only if imaging procedures showed signs indistinguishable from malignancy, or if they were highly suggestive for the presence of pus, joint infection or osteonecrosis. The patients were followed up for a minimum of 3 years. Results: All five patients treated solely with antibiotics recovered completely. Three patients were subjected to open biopsy and surgical treatment since they showed radiological signs indistinguishable from malignancy, and two patients due to pus or osteonecrosis. In follow-up, there was one relapse of chronic osteomyelitis 11 months after the first treatment course with surgery and antibiotics. One patient suffering from Ewing's sarcoma as detected by open biopsy was excluded. Conclusion: Our diagnostic procedure was useful to reduce the rate of surgery. Surgical treatment of chronic osteomyelitis is not always neccessary especially in cases of missing necrosis, joint infection and abscess as demonstrated by the complete recovery of our patients treated solely with antibiotics.
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  • 89
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    Annals of biomedical engineering 28 (2000), S. 128-134 
    ISSN: 1573-9686
    Keywords: Hippocampus ; Vigilance states ; Paired-pulse ; Dentate gyrus ; Dentate granule cells ; Evoked response ; Rat ; In vivo studies ; Perforant path ; Maturation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract This study examined the effect of normal development and vigilance state on the modulation of dentate granule cell activity in the freely moving rat at 15, 30, and 90 days of age across three vigilance states: quiet waking, slow-wave sleep, and rapid eye movement sleep. Using paired-pulse stimulation, the paired-pulse index (PPI) was obtained for the dentate evoked field potentials elicited by the stimulation of the medial perforant path. Although significant differences in PPI values were observed during development, no significant vigilance state related changes were obtained. Preweaning infant rats, i.e., 15-day old, exhibited significantly less early (interpulse intervals, IPI= 20–50 ms) and late (IPI = 300–1000 ms) inhibition, and less facilitation (IPI = 50–150 ms) when compared to the 90-day old adult rats during all three vigilance states. PPI values obtained from the 30-day old group fell intermediate between the 15- and 90-day old animals. These changes in PPI values provide a quantitative measure of changes in the modulation of dentate granule cell excitability during normal maturation. They can now can be used to evaluate the impact of various insults, such as prenatal protein malnutrition or neonatal stress, on hippocampal development. © 2000 Biomedical Engineering Society. PAC00: 8717Nn, 8719La, 8719Nn
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  • 90
    ISSN: 1573-9686
    Keywords: Heart ; Left ventricle ; LV contractility ; ESPVR ; Pig ; Rat ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The end systolic pressure–volume relation (ESPVR) has been shown to be a relatively load independent measure of left ventricular (LV) contractility. Recently, several single-beat ESPVR computation methods have been developed, enabling the quantification of LV contractility without the need to alter vascular loading conditions on the heart. Using a single-beat ESPVR method, which has been validated previously in humans and assumes that normalized elastance is constant between individuals of a species, we studied the effects of myocardial infarction on LV contractility in two species, the rat and the pig. In our studies, LV pressure was acquired invasively and LV volume determined noninvasively with magnetic resonance imaging, at one week postinfarction in pigs and at 12 weeks postinfarction in rats. Normalized systolic elastance curves in both animal species were not statistically different from that of humans. Also, the slope of the ESPVR $$\left( {E_{es} } \right)$$ decreased significantly following infarction in both species, while the volume-axis intercept $$\left( {V_0 } \right)$$ was unaffected. These results indicate that a single-beat ESPVR method can be used to measure the inotropic response of the heart to myocardial infarction, and that the basis for this method (i.e., constant normalized elastance) is applicable to a variety of mammalian species. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 8761Lh, 8719Hh, 8719Rr, 8719Ff
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  • 91
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    Annals of biomedical engineering 28 (2000), S. 1101-1115 
    ISSN: 1573-9686
    Keywords: Time–frequency analysis ; Coherence ; Cross correlation ; Nonstationary persistent signals ; Central pattern generator ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract We present a novel time-varying phase spectrum (TVPS) method to quantify the dynamics of coevolution of two persistent nonstationary coupled signals. Based on the TVPS, an instantaneous intersignal phase shift is defined within the primary frequency range in which the two signals are highly correlated. The TVPS is estimated using a fixed-window method or an adaptive-window method. In the latter method, the window length changes dynamically and automatically as a function of change in frequency of the signals. The effects of altering window types and lengths on the accuracy of the estimation of the primary phase shift is assessed by analyzing synthesized linear chirp signals with decaying amplitude and constant relative phase shift or decaying amplitude and changing relative phase shifts. The methods developed are also used for determining the evolution of the primary phase shift among ventral root activities during fictive locomotion in an in vitro rat spinal cord preparation. The analyses indicate that the TVPS method in conjunction with the determination of the primary frequency range, allows determination of both the evolution of the coupling strength and the evolution of the phase shift between two persistent nonstationary rhythmic signals in the joint time–frequency domain. An adaptive window reduces the estimation bias and the estimation variability. © 2000 Biomedical Engineering Society. PAC00: 0230-f, 8780Tq
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  • 92
    ISSN: 0219-1032
    Keywords: c-Fos ; Dopamine ; D1 ; Hippocampus ; Rat ; Synaptic Plasticity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract While dopamine is likely to modulate hippocampal synaptic plasticity, there has been little information about how dopamine affects synaptic transmission in the hippocampus. The expression of IEGs including c-fos has been associated with late phase LTP in the CA1 region of the hippocampus. The induction of c-fos by dopaminergic receptor activation in the rat hippocampus was investigated by using semiquantitative RT-PCR and immuno-cytochemistry. The hippocampal slices which were not treated with dopamine showed little expression of c-fos mRNA. However, the induction of c-fos mRNA was detected as early as 5 min after dopamine treatment, peaked at 60 min, and remained elevated 5 h after treatment. Temporal profiles of increases in c-fos mRNA by R(+)-SKF-38393 (50 μM) and forskolin (50 μM) were similar to that of dopamine. An increase in [cAMP] was observed in dopamine-, SKF-, or forskolin-treated hippocampal slices. By immunocytochemical studies, control hippocampal cells showed little expression of c-Fos immunoreactivity. However, when cells were treated with dopamine, an increase in the expression of c-Fos immunoreactivity was observed after treatment for 2 h. The treatment of hippocampal neurons with R(+)-SKF38393 (50 μM) or forskolin (50 μM) also induced a significant increase in c-Fos expression. These results indicate that the dopamine D1 receptor-mediated cAMP dependant pathway is associated with the expression of c-Fos in the hippocampal neurons. These data are consistent with the possible role of endogenous dopamine on synaptic plasticity via the regulation of gene expression. Furthermore, these results imply that dopamine might control the process of memory storage in the hippocampus through gene expression.
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  • 93
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    Reading and writing 12 (2000), S. 191-218 
    ISSN: 1573-0905
    Keywords: Morphological awareness ; Sensitivity to word relations ; Reading ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Education
    Notes: Abstract The morpho-phonological nature of English orthography is examined in this study of the relation between morphological sensitivity and decoding ability in the latter elementary grades. Children in grades three to six were required to distinguish derivationally-related word pairs (e.g., nature-natural) from foil pairs that are related in spelling but not in morphology (e.g., ear-earth). The materials included both transparently-related (i.e., the second word incorporated the pronunciation of the first, as in person-personal) and complexly-related word pairs (i.e., the second word involved some change in pronunciation, as in atom-atomic). Across two experiments, these items were presented in either oral or written form along with various tests of reading ability, intelligence and phonological awareness. The results indicate that children's recognition of derivational relationships improved with grade-level. As anticipated, there was also a significant association between sensitivity to derivational relatedness and decoding ability which remains significant even when the word pairs were orally presented and even when phonological awareness in taken into account. Both phonological awareness and sensitivity to morphological structure emerge as important factors in decoding skill in the later elementary grades.
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  • 94
    ISSN: 1434-0879
    Keywords: Key words Castration ; Epidermal growth factor ; Insulin-like growth factor I ; Prostate ; Testosterone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) are strong inducers of proliferation to prostate cells cultured in serum-free medium. Accordingly we wanted to study the growth of the prostate gland in castrated rats after treatment with EGF, IGF-I and testosterone. Castrated Wistar rats were treated with growth factors (EGF 35 μg/rat per day; IGF-I 350 μg/rat per day) or testosterone (2 mg/rat per day) for 3 days either immediately after or 10 days after castration. Prostate tissue was examined by stereological and immunohistochemical techniques and by enzyme-linked immunosorbent assay (ELISA). Treatment with EGF inhibited the involution of the prostate (P 〈 0.05), whereas treatment with IGF-I did not affect the prostate involution as compared to castrated controls. EGF treatment significantly increased the endogenous rat EGF in the ventral prostate, but cellular proliferation was not affected. Testosterone treatment increased the weight of the prostate, by increase of all tissue components of the prostate, and significantly increased cellular proliferation. Systemic administration of EGF but not IGF-I decreased the involution of the rat prostate induced by castration. Compared with testosterone, the effects of EGF treatment on the prostate involution were moderate, and the effects of EGF were not related to cellular proliferation.
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  • 95
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    Archives of orthopaedic and trauma surgery 120 (2000), S. 336-337 
    ISSN: 1434-3916
    Keywords: Key words Pulled elbow ; Children ; Trauma ; Immobilization ; Nursemaid’s elbow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the effectiveness in decreasing recurrence of cast application after manual reduction of pulled elbow. Sixty-four children with pulled elbow were randomized into two treatment groups: Group A underwent manipulative reduction followed by splinting the elbow in a flexed and supinated position for 2 days; group B underwent manipulative reduction only. Both groups were examined 2, 5, and 10 days later. None of the 33 patients in group A had a pulled elbow at follow-up. Four (13%) of 31 patients in group B had a pulled elbow 2–5 days later. Immobilizing the elbow for 2 days after manipulative reduction improves the success of treatment of a pulled elbow.
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  • 96
    ISSN: 1434-0879
    Keywords: Key words Bladder ; Rat ; Aging ; Obstruction ; Cystometrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bladder dysfunction in the aging population is a significant problem. However the concomitant presence of other diseases in many patients can make it difficult to distinguish between changes in bladder function and other influences. The present study was designed to study, in aging rats, bladder function and the effect of partial bladder outlet obstruction (BOO) on bladder function. Cystometrics were performed in awake, female Fischer 344 rats of four age groups (6, 12, 18 and 24 months) following subcutaneous implantation of a mediport catheter. Cystometric evaluations were carried out in control rats or those subject to three weeks of BOO. Bladder compliance significantly decreased with aging, which reflected an increase in threshold pressure without changes in bladder capacity. Partial BOO caused development of severe bladder instability. Following BOO, bladder capacity and compliance were significantly increased in all age groups. Threshold pressure was lower in obstructed animals, except for 6-month rats. Younger animals were able to generate a higher contraction pressure to compensate for the BOO, whereas older animals did not. Using an awake model of cystometric measurement, we have demonstrated that aging, by itself can affect bladder function. Furthermore, aged animals respond differently to BOO than younger animals. These results demonstrate that both aging and disease can contribute to bladder dysfunction, and suggest that treatment of bladder dysfunction may require a combination of therapies targeted to multiple etiologies.
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  • 97
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    Urological research 28 (2000), S. 141-146 
    ISSN: 1434-0879
    Keywords: Key words Kidney ; Nitric oxide ; Ischemia-reperfusion injury ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study we attempted to clarify the release of nitric oxide (NO) and its role in the ischemia-reperfusion rat kidney. After right nephrectomy, male Wistar rats were divided into four groups: one sham operated and three groups who underwent ischemia (30 min) and reperfusion of the left renal artery. Thirty minutes prior to ischemia-reperfusion, two groups were injected intraperitoneally with 10 and 30 mg/kg of NG-nitro-l-arginine methylester (L-NAME). Real-time monitoring of blood flow and NO release in the rat kidney was measured with a laser Doppler flowmeter and an NO-selective electrode, respectively. Serum creatinine and blood urea nitrogen (BUN) levels were measured 1 and 7 days after the induction of ischemia-reperfusion. Clamping of the renal artery decreased blood flow to 1–5% of the basal level measured before clamping. After removal of the clip, the blood flow of the 30 mg/kg L-NAME rats was significantly lower than that of the controls. Immediately following the clipping of the renal artery, NO release rapidly increased. After removing the clip, NO release immediately returned to three-quarters of the basal level. Serum creatinine and BUN levels of the ischemia-reperfusion rats were slightly but not significantly higher and those of 30 mg L-NAME rats were significantly higher than those of the control or ischemia-reperfusion rats 1 day and 7 days after ischemia-reperfusion. Our data suggest that NO acts as a cytoprotective agent in ischemia-reperfusion injury of the rat kidney.
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  • 98
    ISSN: 1433-0350
    Keywords: Keywords Syringomyelia ; Chiari I malformation ; Foramen magnum decompression ; Children ; Scoliosis ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The authors studied the role of the sole posterior fossa bony decompression in the management of symptomatic children affected by Chiari type I anomalies. The series in the pediatric literature on this subject were reviewed and compared with that presented in this article. From May 1994 to December 1998, 53 patients (3 months to 26 years) were observed. They were divided into: asymptomatic patients (27), who received no surgical treatment and were only subject to clinical observation; symptomatic patients (brain stem compression 16, syringomyelia 10, including 7 with holocord). All the symptomatic patients were treated with the same surgical approach: bony decompression of posterior fossa with removal of the posterior arch of C-1 and the outer layer of the dura without dural opening. In all 16 (100%) of the 16 patients with brain stem compression the symptoms resolved or improved; in patients with syringomyelia the symptoms were resolved or improved in 94.4% of cases. Two children required further surgery after 13 and 24 months, respectively.This series seems to demonstrate that even a simple extradural surgical approach, with a lower rate of postoperative complications and short stay in hospital, is sufficient to arrest the disease and to improve the symptomatology in a high percentage of cases (97.2%), which is comparable to that achieved with other, more aggressive, procedures.
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  • 99
    ISSN: 1433-0350
    Keywords: Key words Botulism ; Electrophysiology ; Blink reflex ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Electrophysiological studies of a child with presumed botulism showed that the amplitude of the serially and electrically elicited blink reflexes Rl, R2 and R2’ was reduced during recovery. These findings suggest a conduction block of the facial nerves. Other nerve conduction studies and an incremental response to repetitive stimulation demonstrated a block of the presynaptic neuromuscular transmission. Results of the biological tests were negative, but those of electrodiagnosis and clinical examination favored a diagnosis of botulism. A combination of electrically elicited blink reflexes and rapid repetitive stimulation of the peripheral nerves was found to be a sensitive method of assessing the integrity of neuromuscular junctions and the subclinical impairment of muscle nerves.
    Type of Medium: Electronic Resource
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  • 100
    ISSN: 1433-0350
    Keywords: Key words Hydrocephalus ; Endoscopic III ventriculostomy ; Outcome ; MRI ; Cine-MRI ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In order to analyze the surgical outcome according to clinical characteristics and to evaluate the correlation between clinical improvement and neuroimaging changes, we retrospectively reviewed 32 children who had undergone endoscopic III ventriculostomy (ETV) from February 1994 to May 1998. There were 15 boys and 17 girls, with a mean age of 5.2 years (range: 1 month to 13 years). The etiology of the hydrocephalus was primary aqueductal stenosis in 18 patients, secondary aqueductal stenosis caused by tumors in 5, IV ventricle outlet obstruction in 5, and hydrocephalus associated with meningomyelocele in 4. The mean duration of follow-up was 19.4 months (range 1–50 months). Overall, surgical outcome was regarded as good in 21 of 29 patients. Surgical outcome was poor in patients younger than 1 year (P〈0.05). Neuroimaging 1 month after ETV showed a decrease in ventricular size in 11 of the 16 patients with good surgical outcomes. Five showed minimal changes only. In patients with good outcomes, ventricular size tended to decrease as time passed. Resolution of periventricular edema, flow void in the III ventricle on T2-weighted axial images, and cine-MR imaging were sensitive indicators of good outcome. We suggest that ETV be considered as a primary treatment option in patients older than 1 year of age with noncommunicating hydrocephalus. In addition, time factors should be taken into consideration when surgical outcome is judged. Changes in ventricular size could not predict surgical outcome completely in themselves. Therefore, a comprehensive postoperative assessment should be made with the help of T2-weighted MRI and cine-MRI.
    Type of Medium: Electronic Resource
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