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  • 1995-1999  (196)
  • 1980-1984
  • 1999  (196)
  • Rat  (115)
  • Children  (81)
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  • 1995-1999  (196)
  • 1980-1984
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  • 1
    ISSN: 1432-2307
    Keywords: Key words Pyruvate kinase isoenzymes ; N-Nitrosomorpholine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The expression of the pyruvate kinase (PK) isoenzymes L and M2 was analysed in the livers of rats treated with the hepatocarcinogenic agent N-nitrosomorpholine (NNM) in the drinking water. In control animals L-PK expression was restricted to liver parenchymal cells, whereas M2-PK was detected in bile duct epithelial, blood vessel wall, endothelial and Kupffer cells. In rats treated with NNM proliferating oval cells were consistently L-PK negative and M2-PK positive, while the ductal cells of cholangiofibroses were clearly L-PK positive and coexpressed M2-PK. However, no morphological differentiation of ductal cells into hepatocyte-like cells was observed. In the clear and acidophilic cell foci storing glycogen in excess strong staining for L-PK was observed. In glycogen-poor foci induced by NNM a shift from L-PK to M2-PK expression takes place.
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  • 2
    ISSN: 1432-5233
    Keywords: Key words Cadmium ; Diabetes ; VEP ; TBARS ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fifty-two healthy male Swiss albino rats, aged three months, were used in this study. They were divided into four groups: control (c), diabetic (D), cadmium (Cd), and diabetic + Cd (D+Cd). A diabetic condition was induced in D and D + Cd groups by administration of alloxane (5 mg/100 g). After this treatment, Cd and D + Cd groups were injected intraperitoneally with CdCl2 (2 mg/kg week). At the end of the 2-month experimental period, flash visual evoked potentials (FVEPs) of the four groups were recorded with disk electrodes attached with electrode paste 0.5 cm in front of and behind the bregma. The mean latencies off the P1, N1, P2, N2 and P3 components were significantly prolonged in the diabetic group compared with the control group. The mean latencies of P3 in the D + Cd group and of P1 and P3 in the Cd group were longer than those of the control group. P2N2 amplitude of Cd and D + Cd groups were significantly increased compared with the control group. On the other hand, thiobarbituric acid-reactive substances (TBARS) were determined as an indicator of lipid peroxidation. Our data showed that Cd treatment and diabetic condition caused a significant increase of lipid peroxidation in kidney, brain, retina and lens.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Der Radiologe 39 (1999), S. 467-471 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Fremdkörper ; Aspiration ; Diagnostik ; Kinder ; Atemwege ; Key words Foreign body ; Aspiration ; Diagnostic imaging ; Children ; Respiratory tract
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Aspiration of foreign bodies is a common cause of respiratory distress in children between the age of 6 months and 3 years. The diagnosis of radiopaque foreign bodies is easy when the whole respiratory tract is depicted. Nonopaque foreign bodies need a more differentiated diagnostic approach. The first step should be plain films in inspiration and expiration. The performance of additional chest radiographs, fluoroscopy and if need be CT or nuclear scans depends on the result of the plain films. The chest radiograph may reveal a variety of findings, the commonest of which is unilateral air trapping. Rarely, atelectasis, recurrent pneumonia at the same localisation and inspiratory obstruction are found. Combinations of the above-mentioned findings are possible. Moreover, the absence of positive radiological findings does not exclude the diagnosis of foreign body aspiration.
    Notes: Zusammenfassung Die Fremdkörperaspiration stellt eine häufige Ursache für Atemnot und respiratorische Insuffizienz bei Säuglingen und Kleinkindern zwischen 6 Monaten und 3 Jahren dar. Röntgendichte Fremdkörper bereiten bei Abbildung des gesamten Respirationstraktes keine diagnostischen Schwierigkeiten. Nicht röntgendichte Fremdkörper erfordern ein differenzierteres Vorgehen, wobei der erste radiologische Schritt in einer konventionellen Thoraxaufnahme in In- und Exspiration bestehen sollte. Zusätzliche Aufnahmen, Durchleuchtungsuntersuchung und gegebenenfalls die Durchführung einer computertomographischen oder szintigraphischen Untersuchung hängen vom Ergebnis der Thoraxaufnahme ab. Häufigstes radiologisches Erscheinungsbild ist die einseitige exspiratorische Ventilstenose mit Überblähung des betroffenen Lungenabschnittes. Seltener finden sich Atelektasen, rezidivierende Pneumonien an identischer Lokalisation und inspiratorische Ventilstenosen. Kombinationsbilder sind möglich, selbst ein unauffälliges Untersuchungsergebnis kann eine Aspiration nicht ausschließen.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Der Radiologe 39 (1999), S. 472-477 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Fremdkörper ; Ingestion ; Kinder ; Diagnostik ; Key words Foreign body ; Ingestion ; Children ; Diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Foreign body ingestion is not infrequent in infants and children. The diagnosis of radiopaque foreign body ingestion does not pose a major problem. It is crucial to take an X-ray from the pharynx to the level of the pylorus. If a foreign body that might get stuck at the ileocoecal valve is ingested, it is necessary to perform a radiograph of the whole abdomen. Foreign bodies that do not pass the cardia must be extracted endoscopically. In the case of foreign bodies with a smooth contour that have passed the pylorus, parents are advised to check the child’s stool or collect it and bring it for X-raying. If after a week there is no definite evidence that the foreign body has been excreted a follow-up radiograph is carried out. If the foreign body is still in the stomach or duodenum, endoscopy is necessary. The detection of nonopaque foreign bodies can be facilitated by giving oral contrast medium, making the depiction of the foreign body as a filling defect possible. As a complication, perforation can occur, the diagnosis of which may entail the use of sonography, conventional radiography and, to a lesser extent, CT.
    Notes: Zusammenfassung Fremdkörperingestion ist im späten Säuglings- und frühen Kleinkindalter kein seltenes Ereignis. Die Diagnose röntgendichter Fremdkörper bereitet keine Schwierigkeiten. Hierbei ist jedoch zu beachten, daß die Region vom Pharynx bis zum Pylorus abgebildet sein sollte. Wurden Fremdkörper verschluckt, bei denen die Gefahr der Einklemmung in der Bauhin’schen Klappe besteht, sollte das komplette Abdomen bis zum Anus dargestellt werden. Fremdkörper, welche die Kardia nicht passieren, müssen endoskopisch extrahiert werden. Haben glatt begrenzte Fremdkörper den Pylorus passiert, werden die Eltern aufgefordert, den Stuhl zu untersuchen oder zu sammeln und ihn zur röntgenologischen Untersuchung mitzubringen. Sollte der Fremdkörper innerhalb einer Woche nicht auffindbar sein, wird eine Kontrolluntersuchung durchgeführt. Ist der Fremdkörper dann noch im Magen oder im Duodenum, sollte er ebenfalls extrahiert werden. Der Nachweis nicht röntgendichter Fremdkörper kann mittels Gabe von positivem Kontrastmittel als Aussparungsfigur gelingen. Als Komplikation kann eine Perforation auftreten. Hierbei dienen Sonographie, konventionelles Röntgen und gegebenenfalls CT zur Diagnosefindung.
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  • 5
    ISSN: 1432-2307
    Keywords: Key words Medullary thyroid carcinoma ; Basement membrane ; Laminin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Medullary thyroid carcinoma (MTC) originates from C cells, which secrete calcitonin (CT), their specific marker. C cells are located in contact with the basement membrane (BM) of the thyroid follicles, which is partly made up of the laminin-2 isoform synthesized by thyrocytes. During oncogenesis, proliferation of the C cells, invading the centre of the follicles, leads to a break in their normal contact with the BM. As specific interactions of cells with BM components, especially laminins, are important for proliferation and differentiation, we investigated the relationships of normal and neoplastic C cells with laminin in the Wag/Rij rat model of human MTC. Immunocytochemical studies showed a progressive loss of the laminin layer underlying the hyperplastic C cell nodules around the large dedifferentiated tumours. The α2, β1 and γ1 chains of the laminin-2 isoform were synthesized and secreted by rat MTC 6–23 cell cultures and the tumours induced by subcutaneous injection of these cells. In situ hybridization combined with anti-CT immunocytochemistry showed a low expression of α2 mRNA on differentiated C cells and thyrocytes, but an overexpression on immunonegative spontaneous MTC and induced intrathyroid tumours. The high level of α2 gene expression, together with tumour dedifferentiation, suggests a relationship with malignancy.
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  • 6
    ISSN: 1432-2277
    Keywords: Key words Xenotransplantation ; 15-deoxyspergualin ; Guinea pig ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study aimed to investigate the effects of 15-deoxyspergualin (DSG), tacrolimus (FK 506) and cyclosporin A (CyA), alone or in combination, on delayed xenograft rejection (DXR). We used the guinea-pig-to-C6-deficient (C6–)-PVG-rat heart transplantation model, since in this strain combination, hyperacute rejection is avoided. In C6- control rats, the guinea pig xenografts survived for 39.2 ± 6.3 h (mean ± SD). Splenectomy alone resulted in a xenograft survival of 71.8 ± 7.8 h, but the addition of CyA or FK 506 did not further improve graft survival (73.6 ± 3.0 h and 72.0 ± 17.6 h, respectively). In contrast, DSG treatment increased graft survival to a mean of 99.8 ± 9.2 h. When CyA or FK 506 was combined with DSG, no additional effects were observed (105 ± 24.3 h and 95.1 ± 5.6 h, respectively). DSG alone or in combination with FK 506 or CyA resulted in a significant reduction in the serum IgM levels and reduced the deposits of IgM and IgG in rejected grafts. However, all xenografts were still heavily infiltrated by ED1 + macrophages, regardless of the treatment used. Thus, DSG treatment resulted in moderate prolongation of xenograft survival in C6– rats. The effect seems to be related to suppression of xenoreactive antibody production. To prolong xenograft survival further, strategies that inhibit macrophage infiltration seem required.
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  • 7
    ISSN: 1432-1912
    Keywords: Key words Blood pressure ; Endothelium ; Human ; Mesenteric artery ; Rat ; Smooth muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The majority of the findings concerning arterial physiology and pathophysiology originate from studies with experimental animals, while only limited information exists about the functional characteristics of human arteries. Therefore, the aim of the present work was to compare the control of vascular tone in vitro in mesenteric arterial rings of corresponding size (outer diameter 0.75–1 mm) from humans and Wistar-Kyoto rats. The relaxations to acetylcholine (ACh) were clearly less marked in the mesenteric arteries of humans when compared with rats. How-ever, when calcium ionophore A23187 was used as the vasodilator, the endothelium-mediated relaxations did not significantly differ between these species. The NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) attenuated the relaxations to ACh and A23187 in both groups. The endothelium-independent relaxations to the β-adrenoceptor agonist isoprenaline and the nitric oxide (NO)-donor nitroprusside were somewhat lower in human arteries, while vasodilation induced by the K+ channel opener cromakalim was similar between humans and rats. Arterial contractile sensitivity to noradrenaline and serotonin was slightly lower in human vessels, whereas contractile sensitivity to KCl was similar between these species. The contractions induced by cumulative addition of Ca2+ with noradrenaline as the agonist were effectively inhibited in both groups by the calcium channel blocker nifedipine, the effect of which was clearly more pronounced in human arteries. In conclusion, the control of vascular tone of isolated arteries of corresponding size from humans and rats appeared to be rather similar. The most marked differences between these species were the impaired endothelium-mediated dilation to ACh and the more pronounced effect of nifedipine on the Ca2+-induced contractions in human arteries.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Neuroradiology 41 (1999), S. 512-516 
    ISSN: 1432-1920
    Keywords: Key words Meninges ; Tumours ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Childhood meningeal tumours are uncommon and mostly meningiomas. We reviewed the histological and radiological findings in meningeal tumours in six children aged 12 years or less (four benign meningiomas, one malignant meningioma and one haemangiopericytoma). Compared to the adult counterpart, childhood meningiomas showed atypical features: cysts, haemorrhage, aggressiveness and unusual location. MRI features varied according to the site of the tumour, histology, haemorrhage, and presence of intra- or peritumoral cysts. Diagnosis of the extra-axial tumour was relatively easy in two patients with meningiomas, one malignant meningioma and one haemangiopericytoma. MRI findings strongly suggested an intra-axial tumour in two patients with benign meningiomas, because of severe adjacent edema. Awareness of the variable findings of childhood meningiomas and similar tumours may help in differentiation from brain tumours.
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  • 9
    ISSN: 1432-198X
    Keywords: Key words Hypercalciuria ; Idiopathic hypercalciuria ; Bone mineral content ; 1 ; 25-Dihydroxyvitamin D ; Furosemide ; Ammonium chloride ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The relationship between bone mineral status and hypercalciuria is controversial. The effect on bone composition of different forms of hypercalciuria was studied in female rats made hypercalciuric by 7-week administration of oral furosemide (F, n=12), intraperitoneal 1,25-dihydroxy vitamin D (VD, n=11), or oral ammonium chloride (AC, n=12). Seven untreated rats served as controls (C). Hypercalciuria (mg/100 g per 24 h, mean ±SEM) of F (4.3±0.2), VD (4.1±0.4), and AC (3.9±0.3) groups was of similar intensity (C rats 1.3±0.1, P〈0.01). Weight and length gains and serum CO2, sodium, potassium, calcium, and phosphate were no different among the four groups. Bone was studied by dual-energy X-ray absorptiometry of left tibiae. AC rats had significantly less bone area (1.505±0.018 cm2) than VD and C (1.602±0.020 and 1.587±0.019 cm2). Bone mineral content was decreased in F (0.357±0.007 g) and AC (0.362±0.006 g) compared with VD (0.407±0.008 g) and C (0.389±0.009 g) groups. Bone mineral density was different between F (0.231±0.002 g/cm2) and VD and C rats (0.254±0.004 and 0.245±0.003 g/cm2), and also between AC (0.240±0.003 cm2) and VD rats. In these rat models, hypercalciuria of renal origin (F) and hypercalciuria caused by acid load (AC) adversely impaired bone mass.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 13 (1999), S. 800-805 
    ISSN: 1432-198X
    Keywords: Key words In situ hybridization ; Kidney development ; Nephrogenesis ; Phosphatase activity ; Serine/threonine protein phosphatase 2A ; Protein phosphorylation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Several lines of evidence suggest that the serine/threonine protein phosphatase (PP)2A is of vital importance for cell cycle regulation, cell differentiation, and signal transduction. This prompted us to study the expression of the mRNA for PP2A catalytic isoforms α and β in the developing rat kidney using in situ hybridization histochemistry. The expression patterns of the two isoforms were strikingly similar. Both were ubiquitously expressed in early metanephric kidneys. Later in gestation they were expressed in the nephrogenic zone. Strong expression was observed on postnatal day (PN) 10. This was followed by a downregulation at PN20, i.e., when nephrogenesis is completed. The expression in the adult kidney was very weak and mainly confined to the medulla. In a phosphatase activity assay, PP2A accounted for 78% of the total serine/threonine phosphatase activity in embryonic day 15 rat kidneys. PP1 was the main contributor to the remaining activity. In conclusion, PP2A is the major serine/threonine phosphatase in fetal kidneys. The age-dependent expression pattern supports the concept that this enzyme is of particular importance during renal morphogenesis and development.
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  • 11
    ISSN: 1432-198X
    Keywords: Key words Cystinosis ; Cysteamine ; Renal function ; Rat ; Prenatal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The safety of cysteamine after renal transplantation and during pregnancy is an important issue, since girls with cystinosis are in better health on cysteamine therapy and thus more likely to become pregnant. In the first study, cysteamine was given to pregnant rats on days 6.5–18.5 post conception in oral doses of 0, 37.5, 75, 100, and 150 mg/kg per day. The dams were sacrificed on day 20.5, the fetal kidneys removed and prepared for histological examination. In the second study, cysteamine was given to dams on days 6.5–19.5 post conception in oral doses of 0, 37.5, 50, and 75 mg/kg per day. Dams were allowed to give birth naturally and pups were given cysteamine on days 4–21 to yield the same oral doses of cysteamine given to the dam. Renal function was evaluated on day 35. Histological examination of fetal kidneys revealed no changes even in kidneys from fetuses with growth retardation and malformations. Furthermore, there were no alterations in renal function in offspring on day 35. These findings demonstrate that cysteamine therapy does not affect renal development in the rat. Further investigations will be required to prove whether cysteamine therapy has the potential to affect renal development in the human.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Neuroradiology 41 (1999), S. 929-934 
    ISSN: 1432-1920
    Keywords: Key words Magnetic resonance imaging ; diffusion weighted ; Myelination ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the changes in brain water diffusion in childhood as seen on diffusion-weighted MRI in 30 children from 1 day of life to 17 years to provide a data base and to investigate the correlation of diffusion changes with known patterns of white matter maturation. The apparent diffusion coefficient (ADC) and apparent anisotropy (AA) were calculated in numerous regions of the brain to include major white matter tracts and gray matter. ADC and AA values were directly related to the structural maturity and compactness of the white matter tracts and changed with aging in a way that predated early myelination markers such as signal change on T1- or T2-weighted images. Diffusion of water is sensitive to structural changes in the brain such as white matter maturation and may be useful in investigating white matter disorders.
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  • 13
    ISSN: 1432-1831
    Keywords: Key wordsToxoplasma gondii ; Toxoplasmosis ; Rat ; Animal model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is evidence that not only the immune status, but also the genetic predisposition of certain hosts influence the clinical outcome of Toxoplasma gondii infection. By far the majority of our knowledge on genetic and immunological mechanisms involved in control of T. gondii infection has been obtained by studying mouse models, which in terms of clinical outcome of infection differ considerably from humans. Rats which show a rather similar course of infection in comparison to humans have not so far been investigated for effects of genetic differences on course of the infection. In this study we show that, like mice, different strains of rats exhibit a remarkable variation in the number of brain cysts arising from chronic infection. LEW rats seem to be highly resistant to cyst formation, in contrast to F344 rats that are susceptible. In addition, F344 rats express high numbers of γδ T cells during the acute phase of infection, whereas LEW rats express elevated but comparably low numbers of γδ T cells. The RT1 (rat MHC) haplotypes of both strains are identical in the RT1A and RT1B/D regions, which encode the restriction elements for conventional peptide antigens. Consequently, rat strain-specific differences may be useful to define MHC-independent mechanisms of resistance against T. gondii, which may also act in humans.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Der Nervenarzt 70 (1999), S. 1-10 
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Tic-Störung ; Zwangsstörung ; Kinder ; Jugendliche ; Neurobiologie ; Psycho- pharmakologie ; Verhaltenstherapie ; Key words Tic-disorder ; Obsessive-compulsive disorder ; Children ; Adolescents ; Neurobiology ; Psychopharmacology ; Behavior therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In children and adolescents motor/vocal tics and obsessive-compulsive behavior are known to be closely related. Thereby, a continuum of symptoms ranging from single tics to a mixed picture of tics/rituals/obsessive-compulsive traits to clinically relevant obsessions and compulsions could be described. As neurobiological substrates dysfunctions in corresponding cortico-striato-thalamo-cortical circuits (sensorimotor circuit in tic symptomatology, orbitofrontal circuit in obsessive-compulsive behavior) were postulated. For both disturbances behavioral therapy can be used to improve control mechanisms to counterregulate tics and obsessive-compulsive behavior, respectively, and psychopharmacological agents can be administerd to compensate dysbalances in neurotransmitter systems. In case of a mixed symptomatologic picture it is necessary to include interventions for both pols of the symptom-continuum in the therapeutic programme to achieve extensive improvement as a basis for a further positive development of the patient.
    Notes: Zusammenfassung Motorische/vokale Tics und zwanghafte Verhaltensweisen kommen bei Kindern und Jugendlichen häufig gemeinsam vor; dabei kann ein Symptomkontinuum von solitär auftretenden Tics über ein Mischbild von Tics und Ritualen/zwanghaften Gedanken und/oder Handlungen bis hin zu eindeutigen Zwangsphänomenen beschrieben werden. Neurobiologisch können diesem Symptomkontinuum unterschiedlich ausgebreitete Dysfunktionen entsprechender kortiko-striato-pallido-thalamo-kortikaler Regulationssysteme zugrunde liegen. Therapeutisch lassen sich bei beiden Verhaltensauffälligkeiten mittels verhaltenstherapeutischer Techniken Steuerungs- und Kontrollmöglichkeiten zur Gegenregulation der Auffälligkeiten verbessern sowie durch Einsatz von Psychopharmaka Dysbalancen von Neurotransmittersystemen ausgleichen. Bei einem Mischbild von Tics und Zwängen sind therapeutische Interventionen für beide Zielbereiche erforderlich. Nur so können umfassende Verbesserungen erreicht und günstige Entwicklungsbedingungen für die betroffenen Kinder und Jugendlichen eröffnet werden.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    HNO 47 (1999), S. 535-540 
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Hörschäden ; Knalltrauma ; Kinder ; Tinnitus ; Erweiterte Hochtonaudiometrie ; Key words Hearing loss ; Acoustic trauma ; Children ; Tinnitus ; High-frequency audiometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The study presents an analysis of 20 cases of acute acoustic trauma caused by toy pistols. The problem generally involves boys within the age range from 6 to 11 years. Half of the incidents involved attacks with toy pistols used as weapons. Auditory damage appeared in two types, each of which had a notch in the audiogram at the frequency range between 10 and 14 kHz. In children, a shot close to one ear can damage both ears. Great differences in the severity of tinnitus were apparent. The most severe cases of tinnitus were observed in the children with no or minor premanent auditory damage. Children experiencing long periods of uninterrupted tinnitus suffer significantly. This is not only detrimental to family-life but also to the performance of the children at school. The total expenses of treatment for these 20 cases were estimated to be approximately 80,000 DM (40.000 Euro).
    Notes: Zusammenfassung Im Rahmen einer Studie wurden 20 Fälle von Knalltraumata durch Kinderpistolen erfaßt und ausgewertet. Die Problematik betrifft fast nur männliche Personen und schwerpunktmäßig den Altersbereich von 6–11 Jahren. Die Hälfte der Vorfälle waren Angriffe, bei denen die Kinderpistole als Waffe eingesetzt wurde, 2 Typen von Hörschäden sind festzustellen, die jedoch beide durch eine Senke im Bereich von 10–14 kHz charakterisiert sind. Bei Kindern kann der Schuß in eines der Ohren auch das andere Ohr schädigen. Sehr große Unterschiede bestehen im Auftreten von Tinnitus. Die Fälle mit starkem Tinnitus haben keine oder nur geringe bleibende Hörschäden. Die von Knalltraumata betroffenen Kinder leiden oft sehr stark unter langanhaltendem Tinnitus. Dabei wird nicht nur das Leben der Familien beeinträchtigt, sondern auch die schulischen Leistungen der Kinder leiden teilweise sehr stark darunter. Für die Therapie dieser 20 Fälle entstanden Gesamtkosten von ca. 80.000,- DM
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Monatsschrift Kinderheilkunde 147 (1999), S. 328-332 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Asthma bronchiale ; Schulkinder ; Türkische Kinder ; Key words Asthma ; Children ; Turkish children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Objectives: In Germany 4.2% (in Munich 8.6%) of all children under 15 years of age are of Turkish origin, representing the largest ethnic minority in this age group. However, very little is known about the prevalence, severity and management of asthma and other atopic diseases in Turkish children living in Germany. Methods: In a cross-sectional survery the prevalence, severity and treatment of asthma and other atopic diseases was assessed in 7,445 schoolchildren aged 9 to 11 years, living in Munich, southern Germany. Questionnaires were distributed to the parents for self-completion and children underwent skin-prick tests and cold-air hyperventilation challenge. Results: Of those returning the questionnaires (n = 6490/87%), 5,030 (77.5%) were of German and 451 (7%) of Turkish origin. Turkish children showed a significantly lower prevalence of asthma (5.3% versus 9.4%, P 〈 0.05) than their German peers. Furthermore, Turkish children with asthma were less frequently free of symptoms (10.5% versus 34.6%, P 〈 0.05), reported more severe symptoms (41.2% versus 10.9%, P 〈 0.05) and more hospital admissions (55.6% versus 21.6%, P 〈 0.05) due to asthma than German children. Conclusions: The results of this study indicate that despite the lower prevalence of asthma and allergy in the Turkish population living in Germany, asthma is a major health problem for Turkish children. Furthermore, these findings suggest inadequate management of asthma in Turkish children.
    Notes: Zusammenfassung Fragestellung: Türkische Kinder stellen in der Bundesrepublik Deutschland mit 4,2% und in München mit 8,6% den größten Anteil nicht-deutscher Kinder in der Altersgruppe bis 15 Jahren. Wenig ist jedoch bisher über Häufigkeit, Symptome und Behandlung von Asthma bronchiale und anderer atopischer Erkrankungen der türkischen Minderheit in Deutschland bekannt. Methodik: In einer Querschnittstudie wurde bei 7445 Schulkindern im Alter von 9 bis 11 Jahren im Großraum München die Häufigkeit, der Schweregrad und die Behandlung des Asthma bronchiale und anderer atopischer Erkrankungen untersucht. Fragebögen wurden von den Eltern ausgefüllt, Lungenfunktionsuntersuchungen und Hautpricktests wurden bei den Kindern durchgeführt. Ergebnisse: Von denen, die die zugeschickten Fragebögen ausfüllten (n = 6490/87%), waren 5030 (77,5%) deutscher und 451 (7%) türkischer Nationalität. Die türkischen Kinder zeigten eine niedrigere Prävalenz von Asthma bronchiale (5,3% versus 9,4%, p 〈 0,05) und Neurodermitis (1,6% versus 12,9%, p 〈 0,001) im Vergleich zu den deutschen Kindern. Signifikante Unterschiede bestanden zwischen türkischen und deutschen Kindern in Art der Symptome und der Krankheitswahrnehmung. Türkische Kinder mit Asthma bronchiale waren seltener beschwerdefrei (10,5% versus 34,6%, p 〈 0,05) berichteten von schwereren Symptomen (41,2% versus 10,9%, p 〈 0,05) und von einer größeren Anzahl von Krankenhausaufenthalten (55,6% versus 21,6%, p 〈 0,05) aufgrund von Asthma bronchiale. Schlußfolgerung: Die Ergebnisse der Studie legen den Schluß nahe, daß Asthma bronchiale trotz der niedrigeren Prävalenz in der türkischen Bevölkerungsgruppe ein erhebliches Gesundheitsproblem bei türkischen Schulkindern darstellt. Die höhere Anzahl von Fehltagen in der Schule und die deutlich höhere Anzahl von Klinikaufenthalten aufgrund von Asthma bronchiale sprechen für eine mangelhafte präventive Behandlung dieser Erkrankung bei türkischen Kindern.
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  • 17
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    Monatsschrift Kinderheilkunde 147 (1999), S. 351-355 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Latexallergie ; Neuogene Blasenentleerungsstörung ; Kinder ; Key words Latex allergy ; Neurogenic bladder dysfunction ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Objectives: The risk to suffer from natural latex allergy is increased in children with congenital neurogenic bladder dysfunction. We, therefore, evaluated whether or not a serologic screening for detection of sensitization to latex is reasonable in these children. Patients and Methods: 40 children aged from 6 months to 17 years were examined by specific questionnaire-based patient histories, and by determination of total serum immunoglobuline E (total IgE) and natural latex-specific serum immunoglobulin E (latex-IgE) by solid-phase immunoassays. Results: 5 children had a history of allergic reaction to rubber containing materials. In 10 children, latex-IgE was elevated 〉 0.35 kU/l, 6 out of these 10 children without a history of allergic reactions to rubber containing materials. There was a positive correlation of elevated latex-IgE values and the number of former surgical procedures (p 〈 0.006), while no correlation was found between elevated latex-IgE values and clean intermittent catheterization (p = 0.408). Conclusion: Compared to questionnaire-based patient histories, serologic screening examination including determination of latex-IgE values may better identify children at risk to suffer from sensitization to natural latex.
    Notes: Zusammenfassung Fragestellung: Naturlatexallergien kommen bei Kindern mit angeborener neurogener Blasenentleerungsstörung gehäuft vor. Es wurde deshalb untersucht, ob bei dieser Patientengruppe ein serologisches Screening zur Erfassung einer Sensibilisierung gegenüber Naturlatex sinnvoll ist. Patienten und Methode: Untersucht wurden 40 Kinder im Alter von 6 Monaten bis 17 Jahren. Die Untersuchung umfaßte eine gezielte Anamneseerhebung durch Fragebogen sowie die Bestimmung des Gesamtimmunglobulin E (Gesamt-IgE) und des naturlatexspezifischen Immunglobulin E (Latex-IgE) im Serum durch Festphasenimmunoassays. Ergebnisse: 5 Kinder hatten anamnestisch Zeichen einer allergischen Reaktion nach Gummikontakt. 10 Kinder wiesen im Serum erhöhte Werte des Latex-IgE auf, wobei 6 dieser Kinder bisher noch keine Zeichen einer Latexallergie hatten. Pathologische Werte für das Latex-IgE korrelierten statistisch signifikant mit der Anzahl operativer Eingriffe (p 〈 0,0006), nicht aber mit einem durchgeführten sauber intermittierenden Einmalkatheterismus (p = 0,408). Schlußfolgerung: Im Vergleich zur alleinigen fragebogengestützen Anamneseerhebung können durch ein serologisches Screening mit Bestimmung des Latex-IgE mehr Kinder entdeckt werden, die durch eine Sensibilisierung gegenüber Naturlatex gefährdet sind.
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  • 18
    ISSN: 1432-0738
    Keywords: Key words Benzene ; Benzene metabolites ; Diabetes ; Cytochrome P-450 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Benzene is a ubiquitous environmental pollutant primarily metabolized by a cytochrome P-450 (CYP-450) isoenzyme, CYP-450 IIE1. A consistent induction of CYP450 IIE1 has been observed in both rat and human affected by diabetes mellitus. The aim of this study was to evaluate whether streptozotocin (STZ)-induced diabetes determines modifications in the metabolic pathways of benzene in rat. Benzene (100 mg/kg per day, dissolved in corn oil) was administered i.p. once a day for 5 days. Urine samples were collected every day in STZ-treated and normoglycaemic animals, treated and untreated with benzene (n = 10). Urinary levels of trans,trans-muconic acid and of phenol, catechol and hydroquinone (free and conjugated with sulphuryl and glucuronic group) were measured by high-performance liquid chromatography (HPLC). In normoglycaemic rats during the 5 days of treatment with benzene we observed a progressive and significant decrement in the urinary excretion of phenol, phenyl sulphate and glucuronide, catechol, catechol glucuronide, hydroquinone, hydroquinone glucuronide and t,t-muconic acid (P 〈 0.05). In the diabetic animals, conversely, the same metabolites showed progressively increasing urinary levels (P 〈 0.05). Catechol sulphate and hydroquinone sulphate levels were below the instrument's detection limit. In the comparison between diabetic and normoglycaemic benzene treated rats, the inter-group difference was significant (P 〈 0.05) from day 3 of treatment for t,t-muconic acid, and from day 1 for free and conjugated phenol, free and glucuronide catechol and free hydroquinone. In the normoglycaemic rat exposed to benzene the decreasing trend observed in urinary excretion of free and conjugated metabolites may be due to their capability to reduce cytochromial activity. Conversely, in the diabetic rat, urinary levels of benzene metabolites tended to increase progressively, probably due to the consistent induction of CYP-450 IIE1 observed in diabetes, which would overwhelm the inhibition of this isoenzyme caused by phenolic metabolites. Furthermore, the metabolic switch towards detoxification metabolites observed after administration of high doses of benzene is not allowed in the diabetic because of reduced glutathione-S-transferase activity. As a consequence, higher levels of hydroquinone, phenol and catechol, considered the actual metabolites responsibles for benzene toxicity, will accumulate in the diabetic rat. Extrapolating these data to human, we may thus suggest that occupational exposure to benzene of a diabetic subject poses a higher risk level, as his metabolism tends to produce and accumulate higher levels of reactive benzene catabolites.
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  • 19
    ISSN: 1432-0533
    Keywords: Key words Clomethiazole ; Rat ; Spinal cord-injury ; Neuroprotection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clomethiazole (CMZ) has a neuroprotective effect in experimental focal and global forebrain ischemia. This neuroprotective effect may depend on its ability to enhance GABA receptor activity. We have studied the effect of pretreatment with CMZ on motor function recovery and nerve cell damage after spinal cord injury (SCI). Rats were randomized and 30 min before SCI they received a single intraperitoneal dose of CMZ (150 mg/kg) or saline. The spinal cord was injured with a 50 g (4.5 g/mm2) load, applied over the exposed dura, through a curved rectangular plate (2.2 × 5.0 mm) for 5 min at T8–9. The animals became paraplegic 1 day after injury. The rats were evaluated for recovery of hind limb motor function. All animals recovered to some extent over the observation period of 12 weeks. However, hind limb motor function was significantly better in the animals pretreated with CMZ. At 12 weeks the rats were killed and perfused/fixed for morphological investigations. Microtubule-associated protein 2 (MAP2) immunostaining was used to stain neurons and dendrites and Luxol-fast blue to stain myelinated tracts of the white matter. The injured segment of the spinal cord showed severe atrophy, distortion, cavitation and necrosis of grey and white matter. Compared to uninjured controls the transverse sectional area was reduced to 32.7 ± 4% in untreated animals but only to 38.5% ± 4.1 in CMZ-treated animals. MAP2 staining showed that, compared to uninjured controls, grey matter was reduced to 7.4 ± 2.7% in saline-treated injured animals and to 22.7 ± 5.4% in CMZ-treated rats. Our results thus show that in this model CMZ improves hind limb motor function and attenuates the morphological damage to the spinal cord.
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  • 20
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    Anatomy and embryology 200 (1999), S. 413-417 
    ISSN: 1432-0568
    Keywords: Key words Receptor cell ; Axon ; Vomeronasal organ ; Regeneration ; Rat ; HRP-WGA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Chemosensory neurons in the vomeronasal epithelium (vomeronasal neurons) regenerate following experimentally induced degeneration. Transection of the vomeronasal nerves leads to retrograde degeneration of vomeronasal neurons followed by replacement of the cell population. The projection of the axons of regenerated vomeronasal neurons was examined by horseradish peroxidase(HRP) histochemistry and electron microscopy. HRP-wheat germ agglutinin (WGA) was placed on the surface of the vomeronasal organ of the rat. Dense distribution of HRP-labeled fibers was observed in the vomeronasal nerve and glomerular layers in the accessory olfactory bulb (AOB) of the intact rat. At one week after transection, HRP-labeled fibers were not found in the AOB, and no labeled fibers could be observed on the medial surface of the olfactory bulb where the vomeronasal nerve traversed. Three weeks after transection, labeled fiber bundles were observed on the medial surface of the olfactory bulb in all animals. No labeled fibers were detected in the AOB. From 12 to 32 weeks after transection, projection of HRP-labeled fibers was identified in the AOB in 8 out of 26 rats (the incidence of projection was 30%). But the number of projection fibers on the operated side was much smaller than on the control side. Electron microscopy confirmed that the HRP-labeled terminals make synaptic contacts with neurons in the AOB.
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  • 21
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    Anatomy and embryology 200 (1999), S. 521-531 
    ISSN: 1432-0568
    Keywords: Key words Development ; Internal capsule ; Nucleus basalis ; Rat ; Thalamus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study defines several features of the early connections of the developmentally transient perireticular thalamic nucleus of rats. The neocortex of developing rats was injected with either DiI, biotinylated dextran, WGA-HRP (wheatgerm agglutinin conjugated-horseradish peroxidase), fluorescent latex beads or cholera toxin subunit B (CTB) and their brains were processed for tracer detection with standard methods. In general, tracer injections into various regions of the developing neocortex revealed no labelled neurones within the perireticular nucleus, although some of these tracers (WGA-HRP, dextran) labelled many of the amoeboid microglial cells that are found within this nucleus. There were, however, many retrogradely labelled neurones in a region adjacent to the perireticular nucleus, within the nucleus basalis of the basal forebrain (medial edge of globus pallidus). Their identity was confirmed as neurones of the nucleus basalis since they were all were similar in morphology and somal size to neurones that were immunoreactive to NGFr (nerve growth factor receptor), an antigen found only among neurones of the nucleus basalis and basal forebrain. Moreover, double labelling experiments revealed that most, if not all, of the cortically labelled neurones were NGFr-immunoreactive also. Thus, in conclusion, our results suggest that the perireticular nucleus does not project to the neocortex; the only neurones in the general vicinity of the perireticular nucleus that have a cortical projection form part of the nucleus basalis.
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  • 22
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    Anatomy and embryology 200 (1999), S. 533-540 
    ISSN: 1432-0568
    Keywords: Key words Coronary vasculogenesis ; Angiogenesis ; Coronary artery ; Development ; Rat ; Embryonic heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of this work was to address spatiotemporal and morphologic patterns of coronary artery development in rats, based on immunohistochemical and ultrastructural studies of hearts at different stages of prenatal development. Griffonia simplicifolia I lectin and α-smooth muscle antibody were used to demonstrate endothelial cells and/or their precursors and smooth muscle cells, respectively. Ultrastructural examination was performed on ED14–16 hearts to study the morphology of the developing coronary arteries in different regions of the truncus arteriosus and adjacent myocardium. On ED14 endothelial-like cells present within the mesenchyme surrounding the outflow tract penetrated the aortic wall and the truncoconal proximal myocardium. On ED15 these penetrating cells formed vascular clusters, which were the first signs of presumptive vascular channels. Development of the coronary artery proceeded by coalescence of discontinous vascular clusters, formation of the lumen (vascular channels) and establishing a connection of the proximal part with the aorta. The second layer of cells around vascular channels (embryonic media) consisted of mesenchymal cells that were attracted to the immature vessel and were first seen on ED15. At this time no lumenized connection of the coronary artery with the aorta has been seen. After the lumenized connection of the coronary artery with the aorta had been established perivascular cells of the media started to differentiate into vascular smooth muscle, as was shown by α-smooth muscle actin-staining. Further development and differentiation of the media and adventitia proceeded distally (towards the apex).
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  • 23
    ISSN: 1432-0568
    Keywords: Key words Morphogenesis ; Histochemistry ; Lectins ; Carbohydrates ; Salivary glands ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The developmental expression of salivary glycoconjugates was investigated in the rat submandibular and sublingual glands by conventional and lectin histochemistry. By the time of the first differentiation of secretory structures, in spite of similar morphological features, a different histochemical reactivity was detected, accounting for a relevant content of neutral glycoconjugates in the submandibular gland and the occurrence of both neutral and acidic glycoconjugates in the sublingual one. The use of lectins allowed the main changes of secretory components to be noted around gestational day 18. DBA and WGA lectins seemed to act as pre- and post-natal development markers while Con A lectin was indicative of post-natal differentiation. Taken together, data from lectin histochemistry indicated the transitional occurrence of glycoconjugates, probably involved in temporally restricted functions, as well as the co-existence of different secretory components that might also reflect maturational changes of single products.
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  • 24
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    Anatomy and embryology 199 (1999), S. 265-280 
    ISSN: 1432-0568
    Keywords: Key words Cat ; Rat ; Immunocytochemistry ; NADPH-diaphorase ; Thalamus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To gain insight into the cellular organisation of the zona incerta, we have examined the chemoarchitectonic properties of this ”uncertain zone”. The brains of Sprague-Dawley rats and common cats were processed for immunocytochemistry or NADPH-diaphorase histochemistry using standard methods. For the immunocytochemistry, antibodies to γ-aminobutyric acid (GABA), glutamic acid decarboxylase (GAD), parvalbumin, calbindin, tyrosine hydroxylase, somatostatin, serotonin and glutamate were used. Two general patterns of distribution in the zona incerta were seen. First, labelled cells were restricted largely to one of the cytoarchitectonically defined sectors of the zona incerta. For instance, GABA, GAD and parvalbumin-immunoreactive cells were found principally within the ventral sector, NADPH-diaphorase and glutamate-immunoreactive cells within the dorsal sector and tyrosine hydroxylase- and somatostatin-immunoreactive cells within the rostral sector. Second, labelled cells were scattered somewhat across all incertal sectors, with no clear region of concentration. This pattern included the calbindin- and serotonin-immunoreactive cell groups. These results indicate that the zona incerta is made up of many neurochemically distinct cell groups, some of which respect the well-defined cytoarchitectonic boundaries of the nucleus, whilst others do not. This rich neurochemical diversity in the zona incerta suggests that this nucleus may have differential effects on the different structures that it projects to.
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  • 25
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    Zeitschrift für Lebensmittel-Untersuchung und -Forschung 208 (1999), S. 183-188 
    ISSN: 1431-4630
    Keywords: Key words Sulphadimidine ; Fermented sausage ; Carbon-14-labelling ; Rat ; Bound residues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Sulphadimidine (SDM), a drug frequently administered to pigs, is partially converted into other compounds by processing meat to produce raw, fermented sausage. With the aid of 14C-labelled SDM, evidence was obtained that part of the radioactive matter was covalently bound to the matrix. Part of these bound residues could be released in vitro by 4 M HCl at 21  °C or by 0.024 M HCl at 37  °C. Female rats were also able to release bound SDM residues and to excrete these in their urine, in amounts approaching those obtained by treatment with 4 M HCl. Both the parent compound and its main metabolite, N 4-acetyl-SDM, were observed in the urine of rats.
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  • 26
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    Cancer chemotherapy and pharmacology 44 (1999), S. 203-209 
    ISSN: 1432-0843
    Keywords: Key words Vincristine ; Pharmacokinetics ; Repetitive dosing ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: We studied vincristine disposition after 169 weekly i.v. bolus injections in 32 children with acute lymphoblastic leukemia, non-Hodgkin lymphoma, or Wilms' tumor. The aim of the study was to determine intrapatient and interpatient variability in vincristine disposition and demographic, clinical, and biochemical characteristics influencing this variability. Methods: Vincristine plasma concentrations were measured by a high-performance liquid chromatography assay with electrochemical detection. A limited sampling strategy was used based on a bayesian parameter estimation algorithm that is part of the ADAPT II software package. A two-compartment, first-order model was fitted to the data, and pharmacokinetic parameters were calculated from the model using the ADAPT II software. For statistical analysis, analysis of variance (ANOVA), t test, simple and multiple regression analysis, and non-parametric or robust equivalents were used. Results: Results showed a large intrapatient and interpatient variability in distribution half-life, elimination half-life, total body clearance, apparent volume of distribution at steady state, and area under the concentration–time curve. Intrapatient variability was significantly smaller than interpatient variability for all these parameters except distribution half-life. The diagnosis or treatment protocol turned out to be the most predictive characteristic; leukemia and non-Hodgkin lymphoma patients had a significantly higher total body clearance than Wilms' tumor patients. Conclusions: We conclude that both intrapatient and interpatient variability in vincristine pharmacokinetics is large in pediatric cancer patients and that variability, although significantly influenced by diagnosis, largely remains unpredictable.
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  • 27
    ISSN: 1432-0851
    Keywords: Key words Transgenic ; Rat ; EGP-2 ; GA733-2 ; Immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The human pancarcinoma-associated epithelial glycoprotein-2 (EGP-2), also known as 17-1A or Ep-CAM, is a 38-kDa transmembrane antigen, commonly used for targeted immunotherapy of carcinomas. Although strongly expressed by most carcinomas, EGP-2 is also expressed in most simple epithelia. To evaluate treatment-associated effects and side-effects on tumor and normal tissue respectively, we generated an EGP-2-expressing transgenic Wistar rat. To express the cDNA of the EGP-2 in an epithelium-specific manner, the 5′ and 3′ distal flanking regions of the human keratin 18 (K18) gene were used. EGP-2 protein expression was observed in the liver and pancreas, whereas EGP-2 mRNA could also be detected in lung, intestine, stomach and kidney tissues. In this rat, EGP-2-positive tumors can be induced by injecting a rat-derived carcinoma cell line transfected with the GA733-2 cDNA encoding EGP-2. Transgenic rats were used to study specific in vivo localization of an i.v. anti-EGP-2 monoclonal antibody, MOC31, applied i.v. Immunohistochemical analyses showed the specific localization of MOC31 in s.c. induced EGP-2-positive tumors, as well as in the liver. In contrast, in EGP-2-transgenic rats, MOC31 did not bind to EGP-2-negative tumors, the pancreas, or other normal tissues in vivo. In conclusion, an EGP-2-transgenic rat model has been generated that serves as a model to evaluate the efficacy and safety of a variety of anti-EGP-2-based immunotherapeutic modalities.
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  • 28
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    European spine journal 8 (1999), S. 439-443 
    ISSN: 1432-0932
    Keywords: Key words Low back pain ; Children ; Clinical examination ; Questionnaire ; Prevalence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A study was undertaken to analyse the prevalence of low back pain (LBP) and confounding factors in primary school children in the city of Antwerp. A total of 392 children aged 9 were included in the study. All children completed a validated three-page questionnaire and they all underwent a specific lumbar spine oriented medical examination during their annual routine medical school control. This examination was performed by the city school doctors. The questionnaire was composed of easy “yes/no” questions and visual analogue scales. Statistical analysis was performed using Student’s t-test and chi-squared test at the significance level P 〈 0.05. The prevalence of LBP was high. No gender difference was found. A total of 142 children (36%) reported having suffered at least one episode of LBP in their lives. Of these, 33 (23%) had sought medical help for LBP from a doctor or physiotherapist. Sixty-four percent of children reporting LBP said that at least one of their parents suffered from or complained of LBP. This was significantly higher than for the children who did not report having suffered LBP. The way in which the school satchel was carried (in the hand, on the back) had no bearing on the incidence of LBP. There was significantly more LBP in children who reported playing video games for more than 2 h per day, but this was not so for television watchers. The visual analogue scales concerning general well-being were all very significantly correlated with self-reported LBP, with children who reported LBP being more tired, less happy, and worse sleepers. Of the 19 clinical parameters taken down during the medical examination, only one was significantly more prevalent in the group of children reporting LBP: pain on palpation at the insertion site on the iliac crest of the ilio-lumbar ligament. From this study we can establish that there are few clinical signs that can help to single out school children with LBP.
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  • 29
    ISSN: 1432-1084
    Keywords: Key words: Optic nerves ; Neuritis ; Children ; Central nervous system ; MR imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. A 4-year-old boy developed bilateral optic neuritis. Although precise neuro-ophthalmological evaluation was difficult, the diagnosis was made with gadolinium-enhanced MR imaging using fat-suppression technique in the initial stage of the disease. Enhancement and enlargement of the intraorbital and intracanalicular optic nerve were demonstrated bilaterally as well as protrusion of the optic nerve head. The disease responded dramatically to intravenous steroid therapy. The etiologies in children usually differ from those in adolescent and adult patients.
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  • 30
    ISSN: 1432-1106
    Keywords: Key words Coherence ; Entorhinal cortex ; Cortex ; Hippocampus ; Amygdala ; 192 IgG-saporin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Changes in brain electrical activity in response to cholinergic agonists, antagonists, or excitotoxic lesions of the basal forebrain may not be reflective entirely of changes in cholinergic tone, in so far as these interventions also involve noncholinergic neurons. We examined electrocortical activity in rats following bilateral intracerebroventricular administration of 192 IgG-saporin (1.8 µg/ventricle), a selective cholinergic immunotoxin directed to the low-affinity nerve growth factor receptor p75. The immunotoxin resulted in extensive loss of choline acetyl transferase (ChAT) activity in neocortex (80%–84%) and hippocampus (93%), with relative sparing of entorhinal-piriform cortex (42%) and amygdala (28%). Electrocortical activity demonstrated modest increases in 1- to 4-Hz power, decreases in 20- to 44-Hz power, and decreases in 4- to 8-Hz intra- and interhemispheric coherence. Rhythmic slow activity (RSA) occurred robustly in toxin-treated animals during voluntary movement and in response to physostigmine, with no significant differences seen in power and peak frequency in comparison with controls. Physostigmine significantly increased intrahemispheric coherence in lesioned and intact animals, with minor increases seen in interhemispheric coherence. Our study suggests that: (1) electrocortical changes in response to selective cholinergic deafferentation are more modest than those previously reported following excitotoxic lesions; (2) changes in cholinergic tone affect primarily brain electrical transmission within, in contrast to between hemispheres; and (3) a substantial cholinergic reserve remains following administration of 192 IgG-saporin, despite dramatic losses of ChAT in cortex and hippocampus. Persistence of a cholinergically modulated RSA suggests that such activity may be mediated through cholinergic neurons which, because they lack the p75 receptor, remain unaffected by the immunotoxin.
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  • 31
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    Experimental brain research 126 (1999), S. 307-314 
    ISSN: 1432-1106
    Keywords: Key words Striatal dopamine depletion ; Rat ; Locomotion ; Ground reaction forces ; Gait ; Unilateral ; Kinetic ; Centre of mass
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Hemi-parkinsonian rats have preserved postural reflexes but are impaired in initiation of voluntary movements. Surprisingly, these rats can walk and run, suggesting that they can access some compensatory strategy to overcome the rigidity in their impaired limbs. The purpose of the present experiment was to investigate the locomotor compensations made by hemi-parkinsonian rats by measuring the forces exerted by the limbs on the ground throughout the stride during trotting. Rats with unilateral dopamine depletion produced by injection of 6-hydroxydopamine into the nigrostriatal bundle were trained to run back and forth in an alley for food reinforcement. Ground reaction forces were measured in three orthogonal directions using a force plate embedded in the runway. Rats were also videotaped so that limb movements were synchronized with force recordings. Although locomotion was obviously impaired, the affected limbs could support weight and provide some braking forces. In addition, the impaired hindlimb provided significant propulsive force, and a relatively large laterally directed force. Analysis of vertical movement of the centre of mass suggested that the impaired hindlimb was being used partly as a spring. The most significant abnormalities were seen during the diagonal couplet of the impaired forelimb and the unimpaired hindlimb, partly reflecting the important compensatory role of the unimpaired hindlimb. These results demonstrate that this method is useful in the analysis of hemi-parkinsonian gait and provide insights as to how rats can use an impaired limb to produce weight support and propulsion.
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    Experimental brain research 126 (1999), S. 351-358 
    ISSN: 1432-1106
    Keywords: Key words Tooth pulp ; Phrenic nerve ; Electrical stimulation ; C1 spinal neuron ; Digastric electromyogram ; Somatic receptive field ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Effects of electrical stimulation of the ipsilateral tooth pulp (TP) on C1 spinal neurons were determined in 33 anesthetized rats. One hundred and seven neurons responded to TP stimulation. In 10 rats, the activity of 18 C1 spinal neurons and the amplitude of a digastric electromyogram (dEMG, n=10) increased proportionally during the TP stimulation at an intensity of 1–3 times the threshold for jaw-opening reflex (JOR). Excitatory receptive somatic fields were examined in 61 neurons. Somatic field locations of many neurons (67.2%) involved the ipsilateral face, neck, and jaw. The activity of 45 neurons was increased by both noxious pinch and brushing hair. Of the 107 C1 spinal neurons responding to TP stimulation, 55 were tested to determine the effects of electrical stimulation of the ipsilateral phrenic nerve (PN) above the heart. Twenty-eight of 55 neurons tested were excited; no change in activity was seen for the remaining 27 neurons. The activity of six neurons increased as the intensity of PN stimulation was increased. Excitatory receptive somatic fields were determined in 28 neurons, and somatic field locations of 17 neurons (60.7%) included the ipsilateral face, neck, and jaw. Both noxious pinch and brushing hair excited all 28 neurons. These results suggest that there may be the convergence of face, neck, jaw, TP, and PN afferents on the same C1 spinal neurons in the rat.
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  • 33
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    European journal of pediatrics 158 (1999), S. 12-17 
    ISSN: 1432-1076
    Keywords: Key words Alternative medicine ; Complementary therapies ; Critical care ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interest in alternative medicine (AM) is growing. In the USA and Canada, studies showed that 34% of adults and 11% of children use AM. In a prospective cohort study, we investigated the interest in AM among parents of critically ill children in the paediatric Intensive Care Unit (ICU) of a university hospital. From January 1996 to April 1997, we distributed questionnaires to the parents of critically ill children. These strictly anonymous questionnaires were completed at home and returned by mail. Exclusion criteria were short (〈1 day) or repeated hospitalizations, and insufficient proficiency of the German language. The inclusion criteria were fulfilled by 591 patients; 561 received the questionnaire (95%) and 289 (52%) were returned. Of the respondents, 70% would appreciate AM as a complementary therapy on the ICU, 23% found AM equally or more important than conventional medicine whereas only 7% regarded AM as unimportant. On the ICU, 18% used AM; surprisingly 41% of them did not discuss it with physicians or nurses. An additional 21% would have liked to use AM, but did not do so. Typically, AM-users administered AM also at home to their children and themselves. Their children were however, older. Conclusions A substantial proportion of parents used measures of alternative medicine in the intensive care unit, or would have like to do so. However, few had the confidence to discuss this wish with the medical personal. This suggests that alternative medicine is of great interest, even on an intensive care unit. Nevertheless, discussion about alternative medicine seems to be taboo in doctor-patient relations.
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  • 34
    ISSN: 1432-1076
    Keywords: Key words Gastro-intestinal bleeding ; Children ; Jejunal leiomyoma ; Neurofibromatosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gastro-intestinal bleeding is an uncommon presentation in children with neurofibromatosis. Gastro-intestinal involvement caused by jejunal leiomyoma has only been described in adults. To the best of our knowledge, this is the first paediatric case of jejunal leiomyoma associated with neurofibromatosis. We present a 10-year-old girl with a 9-month history of anaemia and low gastro-intestinal bleeding. Abdominal sonography and small bowel series showed a submucosal mass in the proximal jejunum. On surgery, a submucosal tumour was excised and histological examination suggested a diagnosis of “smooth muscle tumour of undetermined malignant potential”. There were no recurrence of symptoms for 4 years after the operation. Conclusion Jejunal leiomyoma should be considered in a child with neurofibromatosis presenting with gastro-intestinal bleeding.
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  • 35
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    European journal of pediatrics 158 (1999), S. S117 
    ISSN: 1432-1076
    Keywords: Key words Stroke ; Coagulation ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Many studies have shown a high percentage of venous thromboses in children to be associated with haematological disorders. However, studies assessing the influence of haemostaseological disorders on paediatric stroke are rare. We compared 26 children with cerebral infarction (median age 2 months, range 0–16.2 years) and 17 with venous thrombosis (median age 4.5 years, range 0–17 years) with regard to prothrombotic risk factors. Prothrombotic disorders were found in 8 out of 26 patients with cerebral infarction (FV Leiden mutation: n = 4; protein C deficiency: n = 1; FV Leiden mutation + protein C deficiency: n = 2; prothrombin mutation G20210A: n = 1) and in 13 out of 17 with venous thrombosis (FV Leiden mutation n = 3; protein C deficiency n = 5; elevated HRGP + PAI: n = 1; combined deficiency of AT, protein C and plasminogen: n = 1; F XII deficiency: n = 1; lupus anticoagulans n = 1; FV Leiden + F XII deficiency + lupus anticoagulans + PAI: n = 1). Comparison of these prevalences with those of 150 healthy paediatric controls showed in children with FV Leiden mutation and/or protein C deficiency an increased risk of cerebral infarction (patients vs. controls: 26.9% vs. 6%; OR 5.77; 95%-CI 1.92–17.3; P = 0.0031) as well as of venous thrombosis (53% vs. 5.3% 19.9; 95%-CI 6–65.6; P 〈 0.0001). This result is in contrast with reports on thrombophilia in cerebral infarction in adult patients. Conclusion Our results indicate that FV Leiden mutation and protein C deficiency may contribute to the multifactorial aetiology of stroke in early childhood.
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  • 36
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    European journal of pediatrics 158 (1999), S. 519-522 
    ISSN: 1432-1076
    Keywords: Key words Pulmonary function test ; Adjustment ; Children ; Prediction equations ; Population specific
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fitting adequate prediction equations for pulmonary function test (PFT) parameters is crucial in the analysis of lung function tests and their interpretation. Our work aimed at studying the necessity of building population specific prediction equations, rather than using prediction equations built-in in commercial equipment. We used as an example results of studies carried out among Israeli schoolchildren. Second to sixth grade children (7–13 years old), 1064 boys and 1211 girls, were studied in Tel-Aviv. PFT (forced vital capacity, forced expiratory volume in 1st second, peak expiratory flow, forced expiratory flow in 50% volume, forced expiratory flow in 75% volume) performed by these children were adjusted for height, weight and age, for each sex separately, by a multiple regression procedure. Predicted PFT parameters of 300 boys and 301 girls aged 7–13 years, living along the southern shore of Israel, were calculated using the equations built for the same aged Tel-Aviv children as well as the prediction equations built-in in the spirometer used. The ratios between the observed PFT parameters in the southern children and their expected values, using the Israeli population specific equations, were around 1.00. Using the built-in equations resulted in ratios around 0.90. Conclusion The development of population specific prediction equations for PFT parameters is necessary. Such equations should be used both in clinical assessment to minimize misclassification (healthy/sick child) and in epidemiological studies.
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  • 37
    ISSN: 1432-1076
    Keywords: Key words HIV-1 ; T-cells ; CD69 ; Activation ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the use of a whole-blood assay that measures spontaneous and activation-induced CD69 expression on peripheral blood T-cells in vitro for assessment of T-cell function in HIV-1-infected paediatric patients. Heparinized venous blood from 28 HIV-1 positive children and adolescents and 23 healthy controls was incubated for 4 h with or without 5 μg/ml phytohaemagglutinin (PHA). Thereafter, analysis of CD69 expression on CD4+ and CD8+ T-cells was done by flow cytometry; simultaneously we determined CD4+ T-cell counts and plasma HIV-1 viral load. Neither spontaneous nor PHA-induced CD69 expression differed significantly between HIV-1 positive patients and healthy controls. However, T-cells from HIV-1 positive patients with plasma HIV-1 viral load levels above 70 × 103 copies/ml showed a higher spontaneous CD69 expression than T-cells from patients with lower plasma viral load levels in different stages of the disease. Antiretroviral treatment in four patients reduced spontaneous CD69 expression in CD4+ T-cells and PHA-induced CD69 expression in CD4+ and CD8+ T-cells significantly after 8 weeks of therapy. Conclusion Spontaneous and activation-induced expression of the early (activation) antigen CD69 on peripheral blood T-cells does not distinguish HIV-1 positive patients from HIV-1 negative healthy controls and is not correlated with peripheral blood CD4+ T-cell counts. This test may not be a reliable marker for functional T-cell deficiency during early stages of HIV disease. Increased spontaneous as well as PHA-induced CD69 expression on T-cells from HIV-1-infected children and adolescents in vitro may rather reflect HIV-induced pre-activation of T-cells in vivo.
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  • 38
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    European journal of pediatrics 158 (1999), S. 662-667 
    ISSN: 1432-1076
    Keywords: Key words Somatosensory evoked potentials ; Far-field potentials ; Achondroplasia ; Foramen magnum stenosis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Children with achondroplasia may have high cervical myelopathy due to stenosis of the cranio-cervical junction resulting in neurological disability and an increased rate of sudden death. To detect myelopathy we recorded somatosensory evoked potentials (SEPs) after median nerve stimulation in 30 patients with achondroplasia aged 13 months to 18 years (mean 6 years). In addition to the conventional technique of recording the cortical N20 and the central conduction time (CCT), we employed a noncephalic reference electrode recording the subcortical waveforms N13b and P13, generated near the cranio-cervical junction. The findings were related to the clinical status and MRI results. Eighteen patients had MRI evidence of spinal cord compression with indentation or narrowing of the upper cervical cord, and 13 showed signs of myelomalacia. Seven patients had neurological abnormalities. The sensitivities of the SEPs were 0.89 for cervical cord compression, 0.92 for myelomalacia and 1.0 for the clinically symptomatic patients. There were no false-positive results. The subcortical SEPs were more sensitive than the conventional recordings. However, the conventional SEPs were highly specific in the most severely affected patients; here the specificity was 1.0 for patients with myelomalacia and 0.96 for symptomatic patients. Postoperative SEPs improved after occipital decompression in two children. Conclusion The analysis of somatosensory evoked potentials, in particular of subcortical tracings, is useful in the detection of early cervical myelopathy in children with achondroplasia. Early neurosurgical decompression may prevent irreversible damage.
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  • 39
    ISSN: 1432-1076
    Keywords: Key words Heparin treatment ; Heparin-induced thrombocytopenia ; HIT antibodies ; Children ; Catheter patency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The immunological form of heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse reaction of heparin medication. It is mediated by multimolecular complexes consisting of platelet factor 4 (PF4)-heparin-IgG which bind to platelets via platelet Fcγ receptors. Cross-linking of multiple Fcγ receptors results in platelet activation, platelet aggregation and enhanced thrombin generation with a increasing risk of developing new thrombosis. In children, data on HIT are sparse. This review of the literature reports on 8 children aged 3 months to 15 years and 14 newborns suffering from HIT. Additionally, we report one new case treated with danaparoid sodium. Thrombotic complications were venous (n = 12) and arterial (n = 15). The children received heparin either for a spontaneous thrombotic event, for severe cardiac diseases or to maintain patency of intravascular catheters which are used for nutrition, blood sampling, and for application of medication. After diagnosis of HIT they were further anticoagulated with aspirin, warfarin, danaparoid sodium, lepirudin or low molecular weight heparin. Conclusion Although HIT is less frequently reported in newborns and children, paediatricians should be aware of HIT in childhood as a potential complication of heparin application. The widespread practice of flushing catheters with heparin should also be debated in view of the risk of triggering the primary immune-response of HIT. In 1999, treatment options for further parenteral anticoagulation of HIT patients are danaparoid sodium (a low-molecular weight heparinoid) and lepirudin (a direct thrombin inhibitor).
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  • 40
    ISSN: 1432-1076
    Keywords: Key words Factor V G1691A ; Prothrombin G20210A ; Lipoprotein (a) ; Central venous lines ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the role of inherited thrombophilia in the development of central venous line (CVL)-related thrombosis, the following parameters were determined in 77 pediatric-oncologic patients with CVL: activated protein C (APC)-ratio, factor V (FV) G1691A and prothrombin G20210A mutation, protein C, protein S, antithrombin, coagulation factor XII, lipoprotein (a) and homocysteine. An inherited prothrombotic risk factor was found in 17 patients (23%). Four out of 14 patients with a single defect (hyperlipoproteinemia, heterozygous FV G1691A and prothrombin G20210A mutation, protein C deficiency type I) and all three patients with combined defects (heterozygous FV G1691A mutation combined with heterozygous prothrombin G20210A variant, protein S deficiency or hyperlipoproteinemia) suffered from CVL-related thrombosis. In 11 out of 77 patients (14%) a CVL-related thrombosis was detected. In 2 children thrombosis occurred a few days after asparaginase therapy and in another three thrombosis was associated with CVL-related septicemia caused by Staphylococcus epidermidis. After removal of CVL, thrombosis was detected in 5 children, in 2 without clinical symptoms but in the presence of inherited prothrombotic risk factors. Conclusion The present study demonstrates the clinical importance of CVL in combination with inherited thrombophilia in the development of thrombosis in pediatric-oncologic patients. Before or shortly after insertion of CVL, patients should be tested for the presence of factor V G1691A mutation, prothrombin G20210A variant and increased lipoprotein (a) values.
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  • 41
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    European journal of pediatrics 158 (1999), S. S154 
    ISSN: 1432-1076
    Keywords: Key words Veno-occlusive disease ; Antithrombin ; Children ; Chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hepatic veno-occlusive disease (VOD) is a well-known complication of chemotherapy in Wilms tumor patients, particularly young children. Although this complication resolves uneventfully in most patients, fatal cases have been reported. Severe VOD after transplantation has a high mortality rate ranging from 45% to 98%. New hemostatic therapeutic strategies have significantly improved the prognosis of VOD. Chemotherapy-related VOD in Wilms tumor usually has a good prognosis. We describe two patients with Wilms tumor and one with acute lymphoblastic leukemia, who developed severe veno-occlusive disease of the liver according to the Baltimore criteria while undergoing chemotherapy; the symptoms were hepatomegaly, ascites, hyperbilirubinemia, weight gain and, in one patient, short-term lethargy. Elevated LDH levels of 872 to 12,000 U/l were observed in our patients. All patients had thrombocytopenia between 29,000 and 40,000/μl and decreased antithrombin (AT) and protein C levels; two patients had gastrointestinal bleeding. All patients developed a coagulopathy because of severe hepatic dysfunction. Two patients received low-dose heparin at the onset of VOD. The thrombolytic therapy was rapidly changed to AT supplementation (20–80 IU/kg bw 2× per day) without heparin when thrombocytes were very low or gastrointestinal bleeding occurred. Resolution of VOD was observed in all patients receiving AT alone. The chemotherapy was discontinued in a patient with accidental actinomycin D overdosage in view of the severity of symptoms. The remaining two patients received chemotherapy according to the therapy protocol after restitution. All patients survived without sequelae with a median follow-up of 28 months (range 8–48 months). Conclusion Hepatic veno-occlusive disease is a rare but increasingly recognized complication in pediatric cancer patients receiving conventional chemotherapy. AT supplementation constitutes a good alternative treatment of severe VOD in comparison with other thrombolytic therapies, particularly in patients at high risk of bleeding.
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  • 42
    ISSN: 1432-1076
    Keywords: Key words Antithrombin concentrate ; Children ; Septicaemia ; Acquired antithrombin deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Consumption coagulopathy is a serious problem in childhood. In addition to treatment of the underlying disease, consumption coagulopathy was previously treated with heparin. Nowadays it is treated by substitution of coagulation factors, especially antithrombin (AT) concentrate, alone or in combination with heparin. In this pilot study we administered AT concentrate (dosage 80 U/kgbw/d), without additional heparin treatment, to 29 children beyond infancy with acquired AT deficiency. Antithrombin, platelet count, fibrinogen, PT, and APTT were assayed before and during the course of AT substitution. These coagulation parameters returned to normal 48 hours after normalisation of the plasma AT level. AT levels normalised within 24 h of initial substitution in all children. Lethal outcome due to the underlying disease was observed in only two children. Conclusion Data of this pilot study suggest that, concomitantly with the treatment of the underlying disease, consumption coagulopathy in childhood can be managed successfully with early substitution of AT concentrate.
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  • 43
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    Experimental brain research 126 (1999), S. 501-508 
    ISSN: 1432-1106
    Keywords: Key words Spinal cord ; Wide-dynamic-range neurons ; Tail formalin ; Sciatic afferences ; Thermal stimulation ; Facilitation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A recent model of formalin injection in the tail induced a facilitation of the hindpaw withdrawal reflexes. In the present work we tried, after injecting formalin into the tail of the albino rat, to determine the spontaneous activity and response changes of lumbar sciatic wide-dynamic-range neurons to thermal stimulations of the paw at 45°C and 48°C (the respective thresholds for noxious and non-noxious thermal stimuli). The experiments were carried out with multiple recording electrodes placed in a comb array in the lumbar segments of the spinal cord at L4–L6 level in the sciatic projection field. A significant facilitation of the spontaneous activity was already evident 2 min after injection; at 5 min there were strong facilitations to the thermal stimuli. Stimuli at 45°C, often ineffective prior to the formalin injection, became strongly excitatory. Stimuli at 48°C evoked more conspicuous responses. This facilitatory effect on spontaneous and thermal responses followed a time-course comparable to that described for the excitations seen after paw formalin injection, but the duration was more prolonged, lasting more than 2 h. These data indicate a facilitatory role of the formalin effects on spinal sciatic neurons after injection in the tail. It is proposed that the mutual effects of spinal neurons in distant spinal segments could explain the facilitation and such a time-course, and that a role in the development of prolonged pain could be envisaged.
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  • 44
    ISSN: 1432-1106
    Keywords: Key words Spatial function ; Water maze ; Procedural learning ; Cerebellum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recently, we demonstrated the prevalent role of cerebellar networks in the acquisition of the procedural components of spatial information by testing hemicerebellectomized (HCbed) rats in a classical spatial task, the Morris water maze (MWM). As procedures used in the water maze are a mixture of different components (that is, general procedures, exploration procedures, direct reaching procedures), for optimally solving a spatial task all procedural components must be opportunely managed. Thus, severely impaired procedural learning of cerebellar origin can be better comprehended by fractionating the procedural facets. To this aim, a two-step water-maze paradigm was employed. Normal rats were first trained to search for a hidden platform moved to a different position in each trial, utilizing a water maze setting in which visual cues were abolished by heavy black curtains surrounding the tank. In this paradigm, normal animals solved the task by using general and exploration procedures, but they could not use direct reaching skills. A subgroup of these pretrained animals was then HCbed and, after recovery from cerebellar lesion, was tested in a water maze with normal environmental cues available, a paradigm in which normal animals develop abilities for reaching the target with very direct trajectories. Pretrained HCbed animals, however, did not display the typical spatial deficits of naive HCbed rats, persisted in exhibiting the scanning strategy learned during pretraining, and never displayed direct reaching skills. In conclusion, cerebellar networks appear to be involved in the acquisition of all procedural facets necessary for shifting behavior within the maze until direct reaching of the platform. The lack of flexibility in changing exploration strategies displayed by pretrained HCbed rats is interpreted by taking into account the well-known cerebellar frontal interplay sculpting a specific cerebellar role in the acquisition of spatial procedural steps.
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  • 45
    ISSN: 1432-1076
    Keywords: Key words Coagulation ; Fibrinolysis ; Head injury ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was designed to evaluate the post-trauma haemostatic changes in 27 children with severe cranio-cerebral trauma defined by a modified Glasgow Coma Score (GCS) 〈10. Blood samples for coagulation studies (fibrinogen, von Willebrand factor (vWf), factor VIII:C, antithrombin, protein C, plasminogen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI), D-dimer) were obtained within two hours of admission, 24 h later, and on days 3–5, 7–9, 21 and 35. Data of this study indicate that alterations of coagulation in paediatric patients are similar to those in adults: On hospitalisation, activated haemostasis was found with decreased fibrinogen, antithrombin and protein C along with enhanced t-PA and PAI. Twenty-four hours later, hypercoagulability with significantly increased vWF and fibrinogen started, with a peak level within the second week. Within 24 h of admission, 17 children developed disseminated intravascular coagulation (DIC) with a clear-cut decrease of antithrombin and fibrinogen together with platelet consumption and enhanced D-dimer. The outcome of children with DIC was significantly poorer than in those without DIC. Complete recovery was seen in five patients; sequelae no handicap and moderate disability were each found in six patients. Severe disability was diagnosed in two children, and fulminant DIC with lethal outcome occurred in eight patients. The GCS (P 〈 0.01) and the occurrence of DIC (P 〈 0.005) showed the strongest association with the patients' clinical outcome. Conclusion Our data underline the significance of post-trauma disturbances of the haemostatic system for the clinical course and outcome in children with severe cranio-cerebral injuries.
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  • 46
    ISSN: 1432-1084
    Keywords: Key words: Lung disease ; Pneumoconiosis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. We report two cases of children with malignancies and subpleural nodules found on computed tomography (CT) scan. In both cases the diagnosis was anthracosis. This pathologic condition has never been reported in children. Causes of anthracosis include a smoking environment, living in urban areas and air pollution.
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  • 47
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    Experimental brain research 126 (1999), S. 200-204 
    ISSN: 1432-1106
    Keywords: Key words Motor development ; Anticipatory postural adjustments ; Bimanual coordination ; Children ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Anticipatory postural adjustments (APA) are needed to perform a movement without perturbing posture. We investigated the development of APA in 3- to 4-year-old children during a bimanual load-lifting task. The task required maintaining a stable elbow position despite imposed or voluntary unloading of the forearm. Although children can compensate the consequences of unloading by using APA, their performance did not reach an adults’ level. In addition, children showed high intra-individual variability in the voluntary situation, revealed by the coexistence of both adult-like and immature patterns in kinematic and electromyographic data. In conclusion, the present study reports that APA, associated with a bimanual load-lifting task, are still being set up in 3- to 4-year-old-children. The intra-individual variability should decrease with age and be associated with a progressive mastering of the timing parameters characterizing APA.
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  • 48
    ISSN: 1432-1106
    Keywords: Key words Protein lateral mobility ; Plasma membrane of brain cells ; Fluorescence recovery after photobleaching ; Concanavalin-A-receptors ; Concanavalin-A-fluorescein conjugate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A new method has been developed for ex vivo preparation of brain cortical cells of BN/BiRijHsd rats to make them suitable for the measurement of the lateral diffusion coefficient of the membrane components by means of fluorescence recovery after photobleaching (FRAP). The method involves chopping the brain cortex into pieces of less than 1 mm. These parts are stained with a fluorescent label (e.g., concanavalin-A-fluorescein, Con-A-FL conjugate) and then gently pressed onto a microscope slide using the coverslip. In the resulting specimen, the largest cells of the cortex can be recognized in phase-contrast image, sufficiently stained by the label and ready for the FRAP measurement. The lateral diffusion coefficient of Con-A-receptor proteins (D p) was measured in such brain cell preparations of 15 female rats in four age groups (5.6–31.8 months) and 11 males in three age groups (13.8–31.8 months). Highly significant negative, linear age correlation of D p (R=−0.9958 in females, and −0.9956 in males) were found, the regression equations being D p,=(8.8311–0.1425 X)−10 and D p█=(9.3240−0.1630 X)−10 cm2/s, respectively, where X is age in months. The data confirm that the lateral mobility of plasma membrane proteins represents an important biomarker of cellular aging in the brain cortical cells of BN/BiRijHsd rats.
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  • 49
    ISSN: 1432-1106
    Keywords: Key words Suprathreshold heat pain ; Adapting temperature ; Temporal parameters ; Spinal dorsal horn neuron ; Descending control ; Rat ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The influence of stimulus temperature rise rate (2.5ºC/s, 5.0ºC/s, and 10.0ºC/s), adapting (baseline) temperature (25ºC, 30ºC, and 35ºC), and duration of peak stimulus temperature (1.0 s, 2.5 s, 5.0 s, and 10.0 s) on responses evoked by noxious heat stimuli of suprathreshold intensity was studied in wide dynamic range (WDR) neurons of the rat spinal dorsal horn. The spinal neuronal responses were compared with human psychophysical data obtained using the same stimuli. Noxious heat stimuli with a peak temperature of 54ºC were applied with a contact thermostimulator to the glabrous skin of the hindfoot in rats or to the palmar skin in humans. With the highest ramp rate and the highest adapting temperature, the sensory and spinal neuronal response latencies were decreased more than expected on the basis of the change in physical parameters of the stimulus. The magnitudes of sensory and spinal neuronal response were independent of the stimulus ramp rate, whereas pain magnitude estimates and spinal neuronal impulse counts evoked by the same peak stimulus temperature were increased with an increase in the adapting stimulus temperature. The onset latencies of pain reactions and spinal neuronal responses were independent of the peak stimulus duration, whereas the latency of the maximum discharge in spinal neurons increased with prolongation of the peak stimulus. The sensory magnitude estimate of pain and the neuronal impulse count were increased with increase in stimulus duration. Following spinalization, the spinal neuronal responses were stronger and the stimulus duration-dependent increase in the impulse count developed faster. Moreover, the peak frequency of spinal neuronal response increased significantly with prolongation of the heat stimuli after spinalization, but not in animals with an intact spinal cord. The results indicate that stimulus rise rate, stimulus duration, and the adapting temperature are important factors in determining the sensory and spinal neuronal responses to high-intensity heat stimuli. The changes in the total impulse counts evoked by varying supraliminal heat stimuli in spinal dorsal horn WDR neurons corresponded well with the changes in pain magnitude estimates in humans. Also, the changes in spinal neuronal response onset latencies were accompanied by corresponding changes in onset latencies of human pain reactions but not with pain magnitude estimates. The effect of spinalization indicated that descending pathways control not only the response magnitude in the spinal dorsal horn WDR neurons but also the temporal characteristics of the spinal neuronal response.
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  • 50
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    Experimental brain research 128 (1999), S. 309-314 
    ISSN: 1432-1106
    Keywords: Key words GABA ; Bromodeoxyuridine ; Proliferation ; Immunohistochemistry ; Retina ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The birthdates of GABAergic amacrine cells in the rat retina were investigated by immunocytochemistry using anti-GABA and anti-bromodeoxyuridine (BrdU) antisera. The ratio of co-localization of GABA to BrdU increased gradually from embryonic-day 13 (E13) and showed a peak value on E18 in the central retina and on E20 in the periphery. After birth, until postnatal-day 3 (P3), a few co-localized cells were observed in the inner nuclear layer (INL). However, in the peripheral retina, co-localized cells were observed in the INL and ganglion cell layer until P5. Our results suggest that the birthdates of GABA-immunoreactive cells vary, depending on cell-type and that there is a temporal lag in the GABA-immunoreactive cell production in the peripheral retina relative to the central retina.
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  • 51
    ISSN: 1432-1106
    Keywords: Key words Learning and memory ; Electrical stimulation ; Parafascicular thalamic nucleus ; Two-way active avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To evaluate whether electrical stimulation of the parafascicular nucleus (PF) can improve short-term (24 h) and/or long-term (21 days) retention of two-way active avoidance, rats were implanted with an electrode at this nucleus (experimental groups) or above it (control groups). After a single 30-trial acquisition session, experimental groups were submitted to a 10-min session of electrical stimulation. Results showed that the simple implantation of an electrode at the posterior PF enhanced by itself the acquisition of two-way active avoidance, in such a way that the subsequent stimulation of this region may have been unable to further improve the performance of the rats. On the other hand, parafascicular stimulation improved the 24-h retention of the task in a site-specific way, since this effect was mainly seen after stimulation of the central PF region. The facilitative effect on 24-h retention could also depend on the level of performance achieved during the acquisition session, because this improvement was only evidenced in poorly learning animals. No effects were found on 21-day retention. The present results confirm the involvement of the PF in learning and memory and the functional heterogeneity of this nucleus.
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  • 52
    ISSN: 1432-1106
    Keywords: Key words Opioids ; µ-Receptors ; κ-Receptors ; Aversion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied the effects of morphine injected either systemically or into the dorsal periaqueductal gray (DPAG) or nucleus accumbens (NA) using conventional and ethological analyses of behavior of rats submitted to the elevated plus-maze test with transparent walls. Intraperitoneal morphine (0.1 mg/kg and 0.3 mg/kg) increased both standard and ethological measures, expressing general exploratory activity such as total arm entries, end-exploration, scanning, head-dipping, and rearing. Morphine 10 (7.6 µg/µl) and 30 nmol (23 µg/µl) injected into nucleus accumbens produced similar effects, which were blocked by i.p. naltrexone (2.0 mg/kg), an opioid antagonist with good affinity for µ-opioid receptors. Morphine injected into the DPAG produced either antiaversive (10 nmol) or aversive effects (30 nmol), which respectively reduced and increased entries and time spent in the open arms and behaviors associated with risk assessment (peeping out, stretched attend postures, and flat back approach). The proaversive effects were inhibited by i.p. norbinaltorphimine (2.0 mg/kg), a selective inhibitor for κ-opioid receptors. These findings support the contention that at least some of the motivational effects of morphine may be due to activation of opioid mechanisms in nucleus accumbens, and DPAG has neural substrates for antiaversive and aversive effects of morphine. Moreover, on the basis of previous and present data obtained in this laboratory, it is suggested that stimulation of µ-opioid receptors inhibits and stimulation of κ-receptors activates the neural substrate of aversion in the DPAG. On the other hand, the increase in exploratory behavior due to interaction of morphine with µ-opioid receptors in the nucleus accumbens may be due to the stimulation of the interface between neural substrates of motivation and motor output in this structure.
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  • 53
    ISSN: 1432-1106
    Keywords: Key words Acetylcholine ; Brain slices ; Cerebral cortex ; Long-term depression ; Rat ; Synaptic plasticity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The ability of layer I activation to facilitate the induction of long-term potentiation (LTP) in layer II/III horizontal connections of motor cortex (MI) was examined in rat brain slice preparations. Field potentials evoked in layer I and layer II/III horizontal pathways were recorded from radially aligned MI sites. While theta burst stimulation (TBS) of layer II/III pathways alone failed to induce LTP, simultaneous TBS of layer I and layer II/III inputs on alternate sides of the recording electrodes induced LTP in the layer II/III input in 8 out of 13 slices (mean change +20±6%; N=13). In the same cases, the layer I connections showed mixed effects: LTP in three cases, LTD in five cases, and no modification in five slices. Despite the facilitatory effect of layer I activation on layer II/III LTP induction, we found that the critical circuitry for this effect was outside layer I. Cutting the layer I fibers selectively in the slice did not prevent layer II/III LTP induction, while cuts preserving only layer I blocked layer II/III LTP after conjoint I+II/III TBS. Cholinergic fibers were evaluated as candidates for the facilitatory effect because they branch widely in both layers and they are thought to participate in synaptic modification. The cholinergic contribution to layer II/III LTP facilitation was investigated using bath application of muscarinic antagonists. Muscarinic blockade prevented facilitation of layer II/III LTP by layer I coactivation. Instead, conjoint stimulation in 10 µM atropine produced long-term depression (LTD) of layer II/III (–18±9%; N=11) as well as of layer I (–21±6%; N=11) horizontal responses. These results indicate that connections formed within layer I are ineffective in promoting LTP in the deeper-lying horizontal connections; the critical route by which layer I stimulation influenced LTP induction required the circuitry in the deeper layers, particularly the cholinergic system. Thus, it appears that diffuse cholinergic afferents provide an additional route to regulate activity-dependent synaptic modificaton in horizontal cortical connections.
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  • 54
    ISSN: 1432-1106
    Keywords: Key words Motor unit ; Contraction ; Stimulation pattern ; Rat ; Medial gastrocnemius
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effects of irregularity in the pattern of stimulation on the tension produced by motor units in the rat medial gastrocnemius muscle were investigated. The effects of decreasing as well as increasing the interpulse intervals were observed for each motor unit in tetani fused to different degrees. For each motor-unit type, it was found that the effects of these changes depended on the extent of tetanic fusion. Decreasing the interpulse interval produced an increase in tension during the tetanus: the more fused the profile of tetanus, the smaller the tension increase. Increasing the interpulse interval resulted in a decrease in tetanic tension. This effect was most prominent when the tetanic fusion index was approximately 0.75. This phenomenon resulted from the prolongation in relaxation when tetanic fusion increased, thereby preventing a decrease in tension when the interpulse interval increased. We also investigated the effects of introducing a short interpulse interval (”doublet”) at the beginning of the stimulation. The doublets produced increased tetanic tension with a more fused profile. However, the doublet enhanced the sensitivity of the tetanus to increases in interpulse interval and decreased its sensitivity to decreases in interpulse intervals. Slow-twitch motor units appeared to be significantly less sensitive to both increases and decreases in interpulse interval than fast-twitch units. This suggests that slow-twitch units are better suited for producing long-lasting contractions with a constant tension level. Conversely, the high sensibility of fast-twitch units to changes in stimulation frequency enhances their participation in regulation of tension of the muscular contraction.
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  • 55
    ISSN: 1432-1106
    Keywords: Key words Thyroid hormone ; RT-PCR ; p75 receptor ; trkA ; trkB ; trkC ; Septum ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Early postnatal application of thyroid hormones to rats results in morphological changes of the septo-hippocampal cholinergic and the hippocampal mossy fiber systems. Modulation in the expression of either neurotrophins and/or their receptors is postulated to be involved in these effects. In a recent study, we showed that, after thyroxine application, the mRNA expression of neurotrophins of the nerve-growth-factor (NGF) family is significantly upregulated both in septum and hippocampus. To test whether the neurotrophin receptors (the low-affinity neurotrophin receptor p75 and the specific high-affinity receptors trkA, trkB, and trkC) were also affected by hormone administration, newborn rats were treated daily with subcutaneous injections of thyroxine until postnatal day 12 (P12) at latest. Control animals received corresponding injections of saline. The pups were sacrificed at defined intervals from P9 to P14. The septal areas and the hippocampi were analyzed using the reverse-transcription polymerase chain reaction (RT-PCR) method for quantification of p75, trkA, trkB, and trkC mRNA levels. Analysis of variance over the total investigation period revealed no significant general increases of the gene expressions of either neurotrophin receptor, neither in the septum nor in the hippocampus, although previous results have shown marked changes in neurotrophin levels. On particular postnatal days, significant upregulation could be observed in hippocampus for trkB and trkC. From these and recent data, we conclude that modulation of neurotrophin expression rather than neurotrophin-receptor expression contributes to the morphological modifications within the hippocampal mossy fiber system and the septo-hippocampal cholinergic system.
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  • 56
    ISSN: 1432-1106
    Keywords: Key words Focal cerebral ischemia ; Photothrombosis ; Reperfusion ; Spontaneous recanalization ; Cerebral blood flow ; Edema ; Penumbra ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In clinical thromboembolic stroke, spontaneous late recanalization is a common feature, but one which has been very sparsely studied experimentally. This study aimed at enabling the study of spontaneous reperfusion and exploring its consequences by modifying a recently developed photothrombotic-stroke model that focuses on the region-at-risk located within an ischemic ring-locus. The exposed crania of male Wistar rats (280–340 g) were subjected to a ring-shaped (5.0 mm outer diameter and 0.35 mm thick) laser-irradiation beam (514.5 nm; 0.89 W/cm2) for 2 min simultaneously with intravenous erythrosin B (17 mg/kg) infusion for 30 s. Transcardial carbon-black perfusion experiments revealed a ring-shaped cortical perfusion deficit at 4 h post-irradiation, which progressively increased at 10, 24, and 48 h, at which time the whole region-at-risk was pale with single distal branches of the middle cerebral artery being extensively narrowed, but not occluded. At 72 h, spontaneous reperfusion was observed in the region-at risk, which was even more pronounced at 7 and 28 days. Cortical cerebral blood flow (cCBF), measured by laser-Doppler flowmetry, was distinctly reduced at 2 min post-irradiation and further decreased slightly during 4 h of recording to ca. 24% of baseline values at the ring locus and 40% in the region-at-risk. In the region-at-risk, cCBF flow values were 23–30% of the baseline at 24–48 h post-irradiation, followed by a relative cCBF increase to 71 and 77% at 72 and 96 h post-irradiation. Brain water content in the ischemic part of the cortex increased steadily from 4 to 48 h post-irradiation; at 72 h, it leveled off and returned to control values at 7 days. In conclusion, by employing a laser beam in the shape of a thin ring, critically sustained cCBF reduction was followed by late, consistent spontaneous reperfusion in the region-at-risk in this novel photochemically induced stroke-in-evolution model.
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  • 57
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    Experimental brain research 125 (1999), S. 239-247 
    ISSN: 1432-1106
    Keywords: Key words Precision grip ; Motor development ; Motor control ; Children ; Object manipulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recent evidence has shown that the anticipatory control of grip and load force is not innate and develops over several years in childhood. The present study examined the development of grasping behavior by quantifying the relationship between grip force and the vertical acceleration of an object. Children and adults were requested to use a precision grip to lift an instrumented object which varied in size and weight. Grip force, grip force rate and the vertical position and acceleration profiles of the test object were measured or calculated. The results demonstrated the presence of distinct developmental milestones in the maturation of precision grip from 2 to 9 years of age. With 2-year-old children, the peak acceleration was negatively correlated (r=–0.51, n=34, P〈0.01) with peak grip force during lifting. By 3 years of age, peak acceleration and peak grip force during lifting became positively correlated (r=0.28, n=104, P〈0.01) and the correlation continued to strengthen up to 9 years of age. Variations in the temporal coupling of both peak grip force and peak acceleration also decreased with maturation. Furthermore, starting at 4-years-old, children clearly controlled the acceleration and deceleration of the object in a symmetrical pattern and used a single burst of grip force rate to grasp the object with some regularity, suggesting that the emergence of an anticipatory control strategy had already begun.
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  • 58
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    European journal of pediatrics 158 (1999), S. 24-28 
    ISSN: 1432-1076
    Keywords: Key words Hashimoto thyroiditis ; Graves disease ; Children ; TSH function-blocking antibody ; Cytotoxic antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a cross-sectional study, 29 children aged between 1 month and 15.3 years (average age 6.8 years) born to mothers with Graves disease or Hashimoto thyroiditis were examined clinically, biochemically, and by sonography of the thyroid gland. At the time of examination all children were clinically euthyroid. Tests of thyroid peroxidase antibody, thyroglobulin antibody, TSH receptor antibody and free thyroxine (fT4) gave normal results. In 3 children subclinical hypothyroidism with elevated TSH and normal fT4 concentrations were found; one of these children had a minor decrease of total thyroxine. Three children with otherwise normal test results had marginally elevated tri-iodothyronine concentrations. Increased antibody titres were present in 8 out of 29 children. TSH function-blocking antibodies were elevated in 8 cases. In addition, cytotoxic antibodies were found in one of the children. The distribution pattern of antibodies was different in each child and unrelated to the type of maternal thyroid disease. Conclusion Children of mothers with auto-immune thyroid disease often have thyroid antibodies without signs of thyroid disease. Whether antibody-positive children have an increased risk of developing thyroid disorders later in life must be examined in a longitudinal study.
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  • 59
    ISSN: 1432-1076
    Keywords: Keywords Liver ; Steatosis ; HIV ; AIDS ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thirty HIV-infected children were cross-sectionally examined for morphologic hepatic abnormalities, using ultrasonography or histology. Abdominal ultrasonography was performed in 27 children. The liver structure was normal in four patients, one of whom had moderate symptoms of the HIV infection and three of them severe symptoms. Abnormal liver structure, compatible with hepatic steatosis, was found in 23 (85%) patients. Five of them were in an early stage of the HIV infection (category N or A), three patients were ranked in category B and 15 patients in category C. Histological examination of the liver was performed in 11 children and steatosis was documented in ten (91%). In seven (70%) of these ten children steatosis had been suspected by ultrasonography. In conclusion, steatosis is common in HIV-infected children. It is non-specific and has no impact on disease, diagnostic evaluation or management. Conclusion Ultrasonography is a sensitive, accurate, non-invasive screening tool. It is more reliable than liver function tests.
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  • 60
    ISSN: 1432-1076
    Keywords: Key words Respiratory chain ; Mitochondria ; Children ; Infancy ; Liver failure ; AbbreviationsMRCD mitochondrial respiratory chain disease ; OLT orthotopic ; liver transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mitochondrial respiratory chain disease may lead to neonatal or late onset liver failure, requiring liver transplantation. In rare cases, the disease is restricted to the liver and the patient is cured after surgery. More frequently, other organs are simultaneously involved and neuromuscular or other extra-hepatic symptoms may pre-exist, or appear in the post-transplant follow up. Pre-transplant evaluation should aim to rule out neurological disease, which may be difficult to differentiate from signs accompanying liver insufficiency. Cerebrospinal fluid lactic acid levels, compared to blood lactate, may be suggestive of central nervous system involvement. Of 11 cases with respiratory chain disorders who had liver transplantation in various centres, 4 are alive and well on follow up, and 6 died, three of them having developed neurological disease post orthotopic liver transplantation. All three patients with initial liver and gastro-intestinal disease died early after transplantation, indicating that these may be poor candidates for this procedure. Conclusion Liver transplantation is feasible in hepatic respiratory chain disorders, but extra-hepatic disease should be ruled out before transplantation. Extra-hepatic manifestations may, however, appear and cause patient death despite successful transplantation.
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  • 61
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    European journal of pediatrics 158 (1999), S. S085 
    ISSN: 1432-1076
    Keywords: Key wordsα1-Antitrypsin ; Liver disease ; Liver transplantation ; Children ; AbbreviationsAATα1-antitrypsin deficiency ; OLT orthotopic liver transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Only a minority of infants born with α1-antitrypsin deficiency will develop serious liver disease during childhood, mostly but not always after neonatal cholestasis. Early prognosis is difficult and all children have to be followed up carefully. The liver disease progresses with varying speed and it lacks specific features. At the time of liver transplantation the young patients have no pulmonary disease induced by the deficiency and in those with renal involvement, the kidney problems can mostly be dealt with by conservative therapy. The peri- and postoperative care of the patients who undergo liver transplantation does not differ from the usual routines.
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  • 62
    ISSN: 1432-1076
    Keywords: Key words Mild head injury ; Fractured bone ; Late sequelae ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two years after an accident resulting in either a mild head injury or a fractured bone, two groups of 22 children each, aged 4–14 years, were examined for the existence of any neurobehavioural symptoms by means of a standardized questionnaire filled out by their caretakers. Selection of the children was based on reports of the Accident and Emergency Department in 1 year. Significantly more symptoms were reported after mild head injury. The main symptoms reported were headache, dizziness, fatigue and memory problems. The total number of symptoms in the children with mild head injury exceeded four times this in the group of children with a fractured bone. Conclusion Even 2 years after a mild head injury there are still residual symptoms in daily life.
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  • 63
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    European journal of pediatrics 158 (1999), S. 298-301 
    ISSN: 1432-1076
    Keywords: Key words Isolated ; Sphenoid ; Sinusitis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acute isolated infectious sphenoiditis is an uncommon, potentially dangerous condition which is often misdiagnosed because of its nonspecific symptoms and paucity of clinical signs. We present eight children with isolated sphenoiditis who were managed in our medical centre during the last 2 years and review the literature. All the patients were adolescents or pre-adolescents and all experienced moderate to severe refractory oppressive headache. Four had a history of sinusitis or allergic rhinitis. None had fever or any other directing clinical sign. Diagnosis was made by cranial computer tomography. All were treated with antibiotics and recovered completely without infectious or neurological complications. Conclusion Acute isolated infectious sphenoiditis should be considered in adolescents and pre-adolescents who present with constant moderate to severe oppressive headache. Awareness of this entity will enable early diagnosis and initiation of antibiotic treatment which is essential to avoid complications and surgical intervention.
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  • 64
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    European journal of pediatrics 158 (1999), S. 362-366 
    ISSN: 1432-1076
    Keywords: Key words Type 1 diabetes ; Children ; Risk factors ; Case control ; Environmental
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to investigate environmental risk factors in the development of type 1 diabetes mellitus in a population-based case-control study. Parents of all patients with manifestation of type 1 diabetes between 1989 and 1994 in Vienna were asked to complete a questionnaire (n = 114). Control children (n = 495), matched for age and sex, were randomly recruited from all schools in Vienna. Fathers of diabetic children were significantly older at the time their children were born than fathers of control children (P = 0.015). Children with diabetes were more likely to be second- or third-born children (P 〈 0.05) and fewer went to kindergarten than the control group children (P = 0.007). No significant difference in duration of gestation, percentage of delivery by caesarean section, birth weight or length was found. Neonatal jaundice was more often observed in the patient group (P = 0.038). Breast feeding was reported by 82.7% of mothers of diabetic children and by 81% of mothers of control children, and the duration of breast feeding was longer in patients than in controls (n.s.). Conclusion In our study, the development of type 1 diabetes mellitus was associated with higher paternal age and neonatal jaundice. No correlation could be found with dietary intake of cow's milk products in early infancy, vaccination and other environmental factors.
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  • 65
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    European journal of pediatrics 158 (1999), S. 550-552 
    ISSN: 1432-1076
    Keywords: Key wordsShigella ; Toxic encephalopathy ; Children ; Brain oedema ; Shiga toxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 6-year-old girl is described who died following rapid neurological deterioration, ending in lethal cerebral oedema. Despite the absence of severe intestinal and metabolic derangement, Shigella was cultured from the stool. Toxic encephalopathy is responsible for death following this rare complication of childhood shigellosis in developed countries. The pathophysiology is unknown. Conclusion Lethal toxic encephalopathy can be caused by Shigella despite the absence of severe intestinal and metabolic derangement. If shigelllosis is suspected, headache may be a first significant sign for the development of toxic encephalopathy. Early recognition and rapid measures to prevent brain oedema may improve outcome.
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  • 66
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Kinderdermatologie ; Exanthem ; Kinder ; Key words Pediatric dermatology ; Exanthema ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Unilateral laterothoracic exanthem a (ULE) is a self-limited, probably infectious-allergic skin disease predominately affecting small children. We describe five such cases. The typical unilaterally located or at least unilaterally dominant exanthem usually starts in the axillary region and is characterized by red, partly confluent papules and fine scales. Two of the children presented with atypical manifestations of ULE. Due to its asymptomatic course, therapy is not necessary in the majority of cases.
    Notes: Zusammenfassung 5 Kinder mit der Diagnose eines unilateralen laterothorakalen Exanthems (ULE) werden vorgestellt. Beim ULE handelt es sich um eine selbstlimitierende, vermutlich infektallergische Hauterkrankung, die hauptsächlich im Kleinkindesalter auftritt. Das typischerweise streng einseitig lokalisierte, immer jedoch einseitig dominierende Exanthem geht meist von der Axillarregion aus und zeigt erythematöse, teils konfluierende Papeln. Zwei der fünf Kinder zeigten auch atypische Hautveränderungen eines ULE. Eine Behandlung ist aufgrund seines überwiegend asymptomatischen Verlaufs in der Mehrzahl der Fälle nicht notwendig.
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  • 67
    ISSN: 1248-9204
    Keywords: Contralateral hernia ; Children ; Incidence ; Predisposing disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is impossible to determine whether or not a child will develop a contralateral hernia after inguinal hernia repair. There exists no risk score for the occurrence of a contralateral hernia. This well-known fact prompted us to perform the underlying study. In a retrospective trial, we reviewed the files of all children operated on for inguinal hernias in our department from January 1986 until December 1994. During this period, we performed 1721 hernia repairs on 1708 children aged 0–16 years. In 96 (5.6%) of these patients, the indication to operate was a contralateral hernia following previous unilateral repair. Comparison of the ages at the time of primary inguinal repair of those children who developed a contralateral hernia (n=96) and those who did not (n=1612) showed a significantly increased incidence of contralateral hernias if the primary operation was performed before the age of two months (p〈0.0001). Diseases predisposing to hernias were found in 38% of all children (prematurity, dystrophia, ventriculo-peritoneal shunt, ascites, asthma). The authors recommend a contralateral exploration for children under the age of two months if they have any predisposing disease.
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  • 68
    ISSN: 1432-0584
    Keywords: Key words Hypergammaglobulinemia ; Polyclonal ; Acute myeloid leukemia ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Polyclonal hypergammaglobulinemia (PHG) associated with hematological malignancies is a rare occurrence. We reviewed our series of 47 children with AML in order to define the prevalence of PHG and its prognostic value in achieving complete remission (CR) after induction treatment. Patients were stratified by immunoglobulin levels into two groups: with PHG and without PHG. CR reached after induction chemotherapy was considered a positive response. Conditional exact tests were used for the statistical analysis; conditional maximum likelihood estimates of the odds ratio (OR) were obtained. Significance levels (p) were determined from two-tailed tests. Twenty-two of 38 (57.9%) evaluable children showed PHG. Children with PHG and AML were more likely to be in CR after first induction treatment (OR=6.25, p=0.021), independent of sex, age at diagnosis, white blood cell count, percentage of blasts in the bone marrow, FAB phenotype, and treatment protocol. Infections seemed to positively influence early treatment response (p=0.038). PHG and infections were not statistically associated (p=0.16). PHG may result from the uncontrolled stimulation of B lymphocytes by cytokines. Infections or transfusions may act as triggers for the immune system, leading to the antileukemic effect seen in patients with AML and PHG going into spontaneous remission. It could be that this activation caused the larger number of CRs observed in our series. Clarification of why PHG exerts a positive influence on children with AML could help us to understand the ways by which the organism is able to control a malignant disease.
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  • 69
    ISSN: 1432-0584
    Keywords: Key words Thrombopoietin ; Interleukin-11 ; Interleukin-6 ; Thrombocytopenia ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We measured serum levels of thrombopoietin (TPO), interleukin (IL)-11, and IL-6 in 90 different samples from 67 pediatric patients with thrombocytopenia (TP). The cytokine levels were determined by enzyme-linked immunosorbent assays (ELISA), and the biological activity of TPO was measured using a cell line transfected with human c-mpl. In patients with impaired megakaryocytopoiesis, as found in diseases such as aplastic anemia, amegakaryocytic TP, or TP with absent radii, we found TPO levels which were highly elevated compared with normal values (mean=261 AU/ml, n=52, vs. 22 AU/ml in healthy controls). In contrast, patients suffering from idiopathic thrombocytopenic purpura (mean=16 AU/ml, n=31) or platelet function defects (mean=23 AU/ml, n=7) demonstrated normal TPO levels. The biological activity tested in the bioassay correlated well with the ELISA data. However, sera of some patients with amegakaryocytic TP demonstrated a remarkably higher biological activity of TPO than expected from the ELISA data. Within the different groups there was no correlation between platelet counts and TPO levels. Only 27% of all samples had elevated levels of IL-11 (mean=450 pg/ml, n=20). Elevated IL-6 serum levels were detected in only 13% of all samples analyzed (mean=42 pg/ml, n=12). We conclude that megakaryocytopoiesis is regulated mainly by TPO, that it is dependent on the platelet and the megakaryocytic mass, and that IL-11 plays an additional role in supporting the platelet production. IL-6 does not appear to be up-regulated in children with thrombocytopenia.
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  • 70
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    Italian journal of neurological sciences 20 (1999), S. 303-307 
    ISSN: 1126-5442
    Keywords: Key words Lyme disease ; Chronic neuroborreliosis ; Children ; MRI ; Demyelinating disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lyme disease is a polymorphic and multisystemic disease caused by Borrelia burgdorferi. Neurological manifestations are found in 10%–50% of cases. We present 2 cases followed for 5 and 6 years of chronic relapsing-remitting neuroborreliosis. Diagnosis of neuroborreliosis in these cases was based on serum and cerebrospinal fluid findings. We discuss clinical, neurophysiological, laboratory and instrumental aspects regarding the difficulties of reaching a correct diagnosis. Further studies, especially in the field of immunology, should help identify the mechanisms responsible for the disease becoming chronic. With this knowledge, it may be possible to design immunological therapies for relapses, and to prevent the evolution of the disease.
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  • 71
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    Italian journal of neurological sciences 20 (1999), S. 119-128 
    ISSN: 1126-5442
    Keywords: Key words Learning ; Development ; Memory ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immediate and 15-min delayed recall of semantically related or unrelated word lists was investigated in 144 normally developing children ranging from 5 to 10 years of age. Immediate recall for the related and unrelated lists increased in a parallel fashion as a function of age. The ability to cluster semantically related items during immediate recall also improved with age. However, in no age class recall scores and clustering indexes were significantly associated. Forgetting rate passing from the last immediate to the delayed recall trial increased for the unrelated list but decreased for the related list of words as a function of age. Results of regression analyses revealed that a developmental increase in forgetting on the unrelated list was actually due to the higher number of words recalled in the last immediate trial by older children. As for the related list, instead, the larger reliance on the clustering strategy of recall by older children was responsible for the progressive reduction of forgetting.
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  • 72
    ISSN: 1432-2072
    Keywords: Key words Acoustic startle response ; Prepulse inhibition ; Sensorimotor gating ; Schizophrenia ; Medial geniculate body ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prepulse inhibition of acoustic startle is the normal reduction in startle response to an intense auditory stimulus when this stimulus is immediately preceded by a weaker prestimulus. Previous studies have shown that several neuroanatomical structures and pathways in the brain are involved in the modulation of prepulse inhibition. In the present study, the functional importance of the medial geniculate body (MG) in the modulation of prepulse inhibition was investigated. To this end, in vivo brain microdialysis probes were used to infuse drugs locally into the MG of awake, freely moving rats simultaneously with startle response and prepulse inhibition measurements in the same animals. Intrageniculate infusion of the sodium channel blocker, tetrodotoxin, significantly reduced prepulse inhibition without affecting baseline startle amplitude. A similar effect was obtained after intrageniculate infusion of the GABAB receptor agonist, baclofen. In addition, intrageniculate infusion of muscimol, an agonist at the GABAA receptor complex, reduced prepulse inhibition, although this effect was obtained at a higher concentration of the drug compared to that of baclofen. These studies suggest that the MG is involved in the modulation of prepulse inhibition and that auditory signals relayed via the MG may be subjected to inhibitory control at this level, involving GABA neurotransmission.
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  • 73
    ISSN: 1432-2072
    Keywords: Key words Methamphetamine ; Dopamine ; Serotonin ; Phentermine ; Fenfluramine ; Drug-discrimination ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To analyze the involvement of dopamine (DA) and serotonin (5-HT) release in the stimulus properties of methamphetamine, two amphetamine analogs that selectively release either brain DA (phentermine) or 5-HT (fenfluramine) were tested for their ability to substitute for methamphetamine in rats discriminating methamphetamine (1.0 mg/kg) from saline. They were subsequently tested for their ability to alter IV methamphetamine (0.06 mg/kg per injection) self-administration in the same species when given as a pretreatment. The DA releaser phentermine, like methamphetamine itself, decreased methamphetamine self-administration (to 70% of baseline responding), but only at a dose of 3.0 mg/kg that fully generalized to the methamphetamine stimulus in the discrimination study. The 5-HT releaser fenfluramine attenuated methamphetamine self-administration to a much larger extent than phentermine (to 37% of baseline responding) at a dose of 1.8 mg/kg that did not generalize to methamphetamine and did not decrease rate of responding in the discrimination study. Tolerance developed to the inhibitory effect of 1.8 mg/kg fenfluramine on methamphetamine self-administration when it was given repeatedly over four consecutive daily sessions. The fenfluramine-induced decrease in methamphetamine self-administration was also attenuated when it was given together with the small 1.0 mg/kg dose of phentermine. These results suggest that DA release plays a dominant role in the discriminative stimulus effects of methamphetamine. However, stimulation of 5-HT release can strongly modify methamphetamine self-administration.
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  • 74
    ISSN: 1432-2072
    Keywords: Key words Ethanol ; Self-administration ; Dopamine ; Acetylcholine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study, the reactivity of striatal dopamine and dopamine-sensitive neurons in superfused striatal slices of ethanol-experienced rats was compared to that of ethanol-naive rats, 3 weeks after oral ethanol self-administration. During the acquisition phase (17 days), rats were offered increasing concentrations of ethanol (from 2 to 10%, 24 h per day) on an alternate-day schedule in a free choice with water. Following 2 weeks of unrestricted 10% ethanol consumption, the highest and lowest drinkers (representing about 25% of the upper and lower extremes of the total population) were selected. Preliminary experiments revealed that both groups of rats displayed a profound increase in ethanol consumption and preference 3 weeks after cessation of ethanol self-administration (deprivation effect). This deprivation effect was associated with an increase in electrically evoked release of [3H]dopamine from superfused nucleus accumbens slices, whereas the evoked [3H]dopamine release from caudate putamen slices remained unchanged. In slices of the caudate putamen, but not in nucleus accumbens slices, postsynaptic dopamine D1 receptor-stimulated cyclic AMP production was also enhanced. In addition, prior ethanol consumption enhanced the electrically evoked release of [14C]acetylcholine release in both striatal regions. Interestingly, the magnitude of these long-term neuroadaptations correlated with the amount of daily ethanol consumption, i.e. neuronal hyperresponsiveness in the striatum was more profound in the high than in the low ethanol drinkers. These data show for the first time that unrestricted free-choice ethanol consumption in rats is associated with a long-term increase in dopaminergic and cholinergic neurotransmission in the nucleus accumbens and caudate putamen. These (and other) neuroadaptations may underlie the enhanced motivation to self-administer ethanol and the maintenance of ethanol consumption long after deprivation.
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  • 75
    ISSN: 1432-2072
    Keywords: Key words NMDA (N-methyl-D-aspartate) ; Schizophrenia ; Prepulse inhibition (PPI) ; Sensory gating ; P50 ; Auditory evoked potentials (AEP) ; Ketamine ; d-Amphetamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Schizophrenic patients suffer from deficits in information processing. Patients show both a decrease in P50 gating [assessed in the conditioning-testing (C-T) paradigm] and prepulse inhibition (PPI), two paradigms that assess gating. These two paradigms might have a related underlying neural substrate. Gating, as measured in both the C-T paradigm (the gating of a component of the auditory evoked potential (AEP)], and PPI can easily be measured in animals as well as in humans. This offers the opportunity to model these information processing paradigms in animals in order to investigate the effects of neurotransmitter manipulations in the brain. In order to validate the animal model for disturbances in AEP gating, d-amphetamine (0.5 and 1 mg/kg, IP) was administered. Gating of an AEP component was changed due to injection of d-amphetamine (1 mg/kg) in the same way as seen in schizophrenic patients: both the amplitude to the conditioning click and the gating were significantly reduced. Next, the effect of the N-methyl-D-aspartate (NMDA) antagonist ketamine (2.5 and 10 mg/kg, IP) was investigated to assess its effects in the two gating paradigms. It was found that ketamine (10 mg/kg) did not affect gating as measured with components of the AEP. However, ketamine (10 mg/kg) disrupted PPI of the startle response to the extent that prepulse facilitation occurred. Firstly, it is concluded that AEP gating was disrupted by d-amphetamine and not by ketamine. Secondly, PPI and the C-T paradigm reflect distinct inhibitory sensory processes, since both paradigms are differentially influenced by ketamine.
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  • 76
    ISSN: 1432-2072
    Keywords: Key words Oxytocin ; SSRIs ; Depression ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The nonapeptide oxytocin is released into systemic circulation in situations of psychosocial interaction, and has been shown to be involved in mechanisms of social bonding and social recognition in laboratory studies. In view of disturbances in psychosocial relationships being a triggering factor for depression and anxiety, it is interesting to note that experimental studies have shown oxytocin to possess antidepressant- and anxiolytic-like actions. Thus, in the present study we examined effects of the SSRI citalopram (20 mg/kg IP) on plasma oxytocin, acutely and upon repeated administration, in adult male Sprague-Dawley rats. Plasma oxytocin, and some functionally related peptides (CCK, gastrin, somatostatin and insulin), were measured by standard radioimmunoassay techniques. Acute citalopram administration produced a statistically significant increase in plasma oxytocin and CCK levels. Administration of citalopram for 14 days did not attenuate the oxytocin-releasing effect to a challenge dose of the SSRI zimeldine (20 mg/kg SC), whereas CCK levels were not increased after the subchronic citalopram treatment. Thus, the SSRI citalopram produces increased plasma oxytocin levels acutely, and there appears to be no or little tolerance to this effect upon repeated administration. There were no, or variable, effects on plasma levels of gastrin, somatostatin or insulin. It is suggested that oxytocin release is an important aspect of the pharmacological actions of SSRIs, and this could be an important contributory factor for the clinical profile of this group of antidepressants with particular efficacy in disorders of psychosocial origin.
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  • 77
    ISSN: 1432-2072
    Keywords: Key words 7-OH-DPAT ; d-Amphetamine ; Dopamine ; Extinction ; Haloperidol ; Progressive-ratio ; Rat ; Self-stimulation ; Ventral tegmental area
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Progressive-ratio (PR) schedules, which have been widely used to study the reinforcing efficacy of various reinforcers (in particular IV psychostimulants), have been very seldom applied to the study of positively reinforcing electrical brain stimulation (EBS). In the present study, rats were required to emit a progressively increasing number of lever-presses (3,4,6,7,9,11,14,16, etc.) for access to successive reinforcers (periods of VTA self-stimulation). Each period of self-stimulation consisted of ten trains of square pulses of EBS; each train was available under a continuous reinforcement schedule. The number of periods of EBS earned during a session was deemed the breaking point (BP). After acquisition and stabilization of self-stimulation, a study was carried out to verify that changes in the strength of the EBS (i.e. changes in the frequency, the intensity or the pulse duration, one parameter at a time) induced changes in the BP. The effects of IP pretreatments with d-amphetamine, the dopamine D3/D2 receptor agonist 7-OH-DPAT and haloperidol were then assessed. Decreases in the strength of EBS decreased the BP. However, increasing the strength above training values resulted in minimal increases in the BP. d-Amphetamine (0.25–1 mg/kg) dose-dependently increased the BP; additionally, when the reinforcer was withheld (i.e. in conditions of extinction, with the stimulator turned off) d-amphetamine was also found to augment the BP. This might indicate that d-amphetamine preferentially potentiated the motivational (non-rewarded presses) aspects of VTA self-stimulation under this type of PR schedule. 7-OH-DPAT had biphasic effects: at low doses (0.01 and 0.03 mg/kg), it tended to decrease the BP while higher doses (1 and 3 mg/kg) robustly increased the BP. Under conditions of extinction, 7-OH-DPAT (1 mg/kg) had a tendency to increase the BP, but this effect was not statistically significant and did not approach the magnitude of effects observed with d-amphetamine. Haloperidol (0.08–0.48 mg/kg IP) dose-dependently reduced the BP, suggestive of a decrease in the reinforcing efficacy of the EBS. These results show that rats can be trained to self-administer EBS of the VTA under a PR schedule of reinforcement and that this behaviour is sensitive to disruption or potentiation of dopaminergic neurotransmission.
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  • 78
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    Psychopharmacology 142 (1999), S. 302-308 
    ISSN: 1432-2072
    Keywords: Key words Alcohol ; Beer ; Craving ; Rat ; Naloxone ; SR 141716 ; Ritanserin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were given two weeks of home cage access to either “near-beer” (a beverage that tastes like beer but contains 〈0.5% ethanol v/v) or near-beer with added ethanol (4.5% v/v), which is simply referred to as “beer”. The two groups of rats (near-beer and beer) were then trained on a “lick-based progressive ratio paradigm” in operant chambers in which an ever increasing number of licks had to be emitted for each successive fixed unit of near-beer or beer delivered. Break points (the ratio at which responding ceased) for near-beer and beer were approximately equal under baseline conditions. Rats were then tested for the effects of the 5HT2A/2C receptor antagonist ritanserin (0.625, 2.5 or 10 mg/kg), the opioid receptor antagonist naloxone (0.625, 2.5 or 10 mg/kg) or the cannabinoid CB1 receptor antagonist SR 141716 (0.3, 1 or 3 mg/kg). All three drugs caused a dose-dependent reduction of break-points and locomotor activity in both the beer and near-beer groups. However, the effects of SR 141716 and naloxone, but not ritanserin, on break-points were significantly more pronounced on rats drinking beer compared to those drinking near-beer. There were no such differential effects of any of the drugs on locomotor activity across the two groups. These results suggest that both SR 141716 and naloxone differentially affect the motivation to consume alcoholic beverages and may thus have potential as drugs for the treatment of alcohol craving.
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  • 79
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    Psychopharmacology 142 (1999), S. 327-333 
    ISSN: 1432-2072
    Keywords: Key words Caffeine ; Nicotine self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The prevalence of tobacco smoking and coffee drinking place nicotine and caffeine among the most used licit drugs in many societies and their consumption is often characterised by concurrent use. The pharmacological basis for any putative interaction between these drugs remains unclear. Epidemiological reports support anecdotal evidence, which suggests that smokers consume caffeine to enhance the euphoric effects of nicotine. The aim of the present experiment was to examine effects of chronic exposure to caffeine on responding maintained by nicotine. Sprague-Dawley rats consuming caffeine (approximately 150–180 mg/kg per day) in their drinking water for 7 days prior to the beginning and throughout behavioural testing acquired intravenous nicotine self-administration (0.03 mg/kg per infusion) more rapidly than did controls. In a cross-over design, exclusion of caffeine brought levels of nicotine self-administration back to baseline, while adding caffeine to the drinking water of control rats increased responding maintained by nicotine over 90%. These findings strongly suggest that caffeine can potentiate the reinforcing properties of nicotine, thus highlighting the importance of environmental factors in shaping and maintaining tobacco smoking.
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  • 80
    ISSN: 1432-2072
    Keywords: Key words Continuous cocaine ; Tolerance ; 5-HT3 receptor ; DA release ; Nucleus accumbens ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously reported that continuous cocaine administration functionally down regulates 5-HT3 receptors in the nucleus accumbens. The current experiments evaluated the duration of behavioral tolerance to cocaine and whether the duration of behavioral tolerance and 5-HT3 receptor down-regulation co-varied. Rats were withdrawn from a pretreatment regimen (40 mg/kg/per day cocaine or 0.9% saline for 14 days) for 1, 7 or 14 days. The rats were either sacrificed, and slices from the nucleus accumbens obtained, or were exposed to behavioral rating procedures. The results indicated that continuous cocaine administration significantly attenuated the ability of mCPBG to facilitate K+-stimulated DA release on days 1 and 7, but not day 14, of withdrawal. Furthermore, continuous cocaine administration induced behavioral tolerance to a cocaine challenge on days 1 and 7, but not day 14, of withdrawal. These results suggest that continuous cocaine administration functionally down-regulates 5-HT3 receptors in the nucleus accumbens, and this functional down-regulation co-varies with the behavioral tolerance induced by continuous cocaine administration. Hence, a functional down-regulation of accumbens 5-HT3 receptors may represent a partial mechanism for the tolerance following continuous cocaine administration.
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  • 81
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    Psychopharmacology 142 (1999), S. 369-374 
    ISSN: 1432-2072
    Keywords: Key words Clozapine ; Withdrawal ; Dependence ; Temperature ; Atypical antipsychotic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: In schizophrenics, clozapine has been reported to induce various withdrawal signs and rapid onset relapse to psychosis on cessation of chronic treatment. Objective: The study was designed to develop an animal model of one aspect of clozapine tolerance and withdrawal using core body temperature measures. Methods: Two groups of 15 female Wistar rats were treated chronically (b.i.d.) with clozapine at 6 or 12 mg/kg per injection for 21 days prior to cessation of drug treatment, withdrawal being studied over 4 consecutive days. Body temperatures were assessed daily throughout the study. Results: Acutely, clozapine induced dose-related hypothermia, to which complete tolerance developed in both groups, the development of tolerance being more rapid in the group treated with 6 mg/kg per injection of clozapine. During withdrawal only the group treated chronically with 12 mg/kg per injection of clozapine showed rapid onset significant hyperthermia. This dissipated progressively over days, and was completely absent after 4 days of withdrawal. Conclusions: Clozapine induced a clear somatic withdrawal sign after chronic treatment. It is suggested that, in future research in both humans and animals, it is important to attempt to differentiate between clozapine withdrawal and clozapine withdrawal-induced relapse to psychosis. It is also important to characterise the clozapine withdrawal syndrome fully in animals; to establish the neurochemical mechanisms involved in such withdrawal; and to determine which novel antipsychotics are most efficacious in inducing clozapine-like withdrawal effects, in suppressing clozapine withdrawal, and in preventing relapse to psychosis in patients being transferred from clozapine to novel atypical antipsychotic drugs.
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  • 82
    ISSN: 1432-2072
    Keywords: Key words Ethanol ; Limited access ; Nicotine ; Mecamylamine HCl ; Rat ; Voluntary intake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Observations in humans suggest that the initial use of tobacco occurs in close temporal proximity to experimentation with alcohol. There have been relatively few research reports, however, examining possible interactions between these two agents. The present experiments examined the effect of nicotine exposure on the acquisition of ethanol drinking behavior in a limited access procedure. In experiment 1, rats were presented with 1-h access to ethanol solutions of increasing concentration for a period of 20 days. Subcutaneous injections of nicotine (0.6 or 1.2 mg/kg salt) or vehicle were administered 30 min prior to each ethanol presentation. Experiment 2 used a similar method, but rats were presented with water along with ethanol during the 1-h test session. Mecamylamine, a nicotinic receptor antagonist, was administered 30 min prior to the nicotine treatment. Nicotine was seen to produce a dose-dependent increase in ethanol drinking behavior which commenced at the 5% ethanol concentration and continued at 8% and again at 10%. In the second experiment, mecamylamine was observed to block completely the nicotine-induced increase in ethanol drinking behavior. The findings suggest that exposure to nicotine can facilitate the acquisition of ethanol drinking behavior in naive rats and that this effect is mediated by nicotine’s interaction at the nicotinic-cholinergic receptor.
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  • 83
    ISSN: 1432-2072
    Keywords: Key words Chlordiazepoxide ; FG 7142 ; Rat ; Diencephalic amnesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The intralaminar thalamic nuclei (ILn) have been implicated as a critical site of pathology in amnesia. Lesions of the ILn have been found to produce behavioral effects comparable to benzodiazepine (BDZ) receptor agonists. We compared the effects of chlordiazepoxide (CDP), a BDZ agonist, and FG 7142, a partial inverse agonist at the BDZ receptor, in rats with thalamic lesions and in unlesioned controls. Delayed matching-to sample (DMS) performances were studied during treatment with ascending doses of CDP, counterbalanced trials with 2.5 mg/kg CDP and saline, ascending doses of FG 7142, and (for unlesioned controls only) counterbalanced trials with saline and higher doses of CDP. CDP had effects similar to the ILn lesion, decreasing response speed and percent correct responding in a delay-independent fashion. These effects were additive with the impairments associated with the ILn lesion. The effects of FG 7142 were more complex. At lower doses, it increased response speed without affecting response accuracy. At higher doses, it diminished both the speed and the accuracy of DMS responding. These results support the hypothesis that ILn lesions and BDZ agonists have similar effects on DMS performance. The biphasic effects observed for FG 7142 are consistent with other evidence that low doses of this drug enhance while higher doses impair memory performance. Although DMS accuracy was not improved, the enhancement observed for response speed provides evidence that partial inverse BDZ agonists have potential utility as treatments for cognitive impairments associated with amnesia.
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  • 84
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Midazolam ; Caffeine ; Cocaine ; Amphetamine ; Pentobarbitone ; Ethanol ; Drug discrimination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: Studies of the discriminative stimulus effects of drug mixtures provide an approach to polydrug abuse and studies on single drugs with multiple effects. Objective: This study was designed to investigate whether the use of the AND-OR procedure increases the specificity of drug mixture discriminations. Methods: Rats were trained to discriminate a mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND-discrimination, n = 8) or to discriminate the same mixture from its component drugs alone (AND–OR discrimination, n = 9). The studies used two-lever operant procedures with a tandem variable interval 1-min fixed ratio 10 schedule of food reinforcement. Results: Under AND-discrimination conditions, there was partial generalization to nicotine and midazolam when each drug was administered singly, and there was no generalization to cocaine, caffeine or ethanol. With the AND-OR discrimination, there was no generalization to any of the preceding drugs administered singly. In “single substitution” tests, nicotine or midazolam was co-administered with the training doses of pentobarbitone and amphetamine, respectively; there was full generalization in the AND-discrimination and partial generalization under AND-OR conditions. Cocaine co-administered with pentobarbitone generalized fully under both procedures, but the dose of cocaine needed was much larger in the AND-OR than in the AND-discrimination. In “dual substitution” tests, mixtures of two novel substances were tested. Mixtures of either nicotine plus midazolam or caffeine plus ethanol produced very marked generalization under AND-discrimination conditions, but were without significant effect in the AND-OR procedure. Throughout the studies, in every instance where comparisons were made, generalization was greater or occurred at lower doses under AND- than under the AND-OR discrimination. Conclusions: The study yielded extensive evidence supporting the hypothesis that the AND-OR discrimination procedure increases the specificity of discriminations based on drug mixtures.
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  • 85
    ISSN: 1432-2072
    Keywords: Key words BC264 ; Cholecystokinin ; CCKB receptor ; Memory ; Ageing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: The implication of CCKB receptors in cognitive processes is far from fully understood. Objective: The present study investigated the effect of propionyl-BC264, a selective agonist of CCKB receptors, in young and old rats. Methods: Cognitive functions were studied in a two-trial recognition memory task developed in our laboratory. Results: It was shown that propionyl-BC264 enhanced information processing in young as well as in old rats when injected (10 μg/kg; IP) immediately after the acquisition phase and before the retrieval trial but not before the acquisition trial. This cognitive enhancing effect was blocked by prior administration of L 365,260, a selective CCKB receptor antagonist. Conclusions: In view of the fact that BC264 is devoid of anxiogenic effects, it could be of value in the treatment of cognitive impairments associated with both normal and pathological ageing.
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  • 86
    ISSN: 1432-2072
    Keywords: Key words Antinociception ; Butorphanol ; Relative efficacy ; Opioid ; Rat ; Stimulus intensity ; Tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: A common treatment strategy for the management of severe pain involves the co-administration of multiple opioid analgesics. Due to the increasing popularity of this practice, it is becoming increasingly important to understand the interactions between clinically employed opioids under a wide range of conditions. Objective: The purpose of the present investigation was to examine the effects of opioid combinations following acute and chronic administration of the low-efficacy mu-opioid butorphanol, and to determine if the effects of these combinations are modulated by the intensity of the nociceptive stimulus. Methods: In a warm-water, tail-withdrawal procedure, rats were restrained and the latencies to remove their tails from 50°C (low temperature) and 55°C (high temperature) water were measured following both acute and chronic administration of butorphanol. Opioids possessing both high (etorphine, levorphanol, morphine) and low [dezocine, (–)-pentazocine, nalbuphine] relative efficacy at the mu receptor were examined. Results: Under acute conditions, etorphine, levorphanol, morphine and dezocine increased tail-withdrawal latencies at both low and high temperatures, whereas (–)-pentazocine, nalbuphine and butorphanol increased latencies only at the low temperature. A dose of 30 mg/kg butorphanol increased the effects produced by these opioids at the low temperature, but antagonized the effects of etorphine, levorphanol, morphine and dezocine at the high temperature. During chronic treatment with 30 mg/kg per day butorphanol, tolerance was conferred to the antinociceptive effects of all the opioids examined, with greater degrees of tolerance conferred to those opioids possessing low efficacy at the mu receptor. During butorphanol treatment, etorphine, levorphanol and morphine increased tail-withdrawal latencies at both water temperatures, dezocine increased latencies at only the low temperature, and (–)-pentazocine, nalbuphine and butorphanol failed to increase latencies at either temperature. A dose of 30 mg/kg butorphanol antagonized the antinociceptive effects of etorphine, levorphanol, morphine and dezocine during chronic treatment, and these effects were observed at both water temperatures. Conclusions: These findings indicate that the interactions between butorphanol and other mu opioids vary quantitatively between low and high stimulus intensities, and between acute and chronic conditions. In most instances, however, these interactions can be predicted from the effects of the drugs when administered alone.
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    Psychopharmacology 143 (1999), S. 293-301 
    ISSN: 1432-2072
    Keywords: Key words Methamphetamine ; Drug discrimination ; Norepinephrine ; Desipramine ; Nisoxetine ; Isoproterenol ; Propranolol ; Methoxamine ; Prazosin ; Clonidine ; Yohimbine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale:Neurochemical and clinical studies indicate involvement of noradrenergic (NE) neurotransmitter system in the actions of methamphetamine. Objective:The present study investigated NE involvement in the discriminative-stimulus effects of methamphetamine. Methods:In Sprague-Dawley rats trained to discriminate 1.0 mg/kg methamphetamine, IP, from saline under a fixed-ratio schedule of food presentation, effects of various NE agonists, antagonists and uptake inhibitors were tested. Results: Desipramine (3.0–18.0 mg/kg) and nisoxetine (5.6–30.0 mg/kg), two selective NE-uptake inhibitors, did not significantly generalize to methamphetamine when administered alone, but 5.6 mg/kg desipramine and 10.0 mg/kg nisoxetine significantly shifted the methamphetamine dose-response curve to the left. The beta NE agonist, isoproterenol (0.56–3.0 mg/kg), and antagonist, propranolol (1.0–18.0 mg/kg), neither generalized to methamphetamine when given alone nor altered the discriminative-stimulus effects of methamphetamine when administered in combination. The alpha-1 NE agonist methoxamine (1.0–5.6 mg/kg) failed to generalize to the methamphetamine training stimulus. When given in combination with methamphetamine, the alpha-1 NE antagonist, prazosin (1.0 mg/kg), shifted the methamphetamine dose-response curve somewhat to the right and partially blocked the discriminative-stimulus effects of the 1.0 mg/kg training dose of methamphetamine, but these changes were not significant or dose-related, with further increases in prazosin dose (1.8–10.0 mg/kg) either producing similar or smaller changes. The alpha-2 NE agonist, clonidine, partially generalized to methamphetamine at doses of 0.1–0.18 mg/kg and increased drug-appropriate responding at lower doses of methamphetamine, but it partially blocked the discriminative-stimulus effects of higher 0.56–1.0 mg/kg doses of methamphetamine over the same dose range. The alpha-2 NE antagonist, yohimbine, also partially generalized to methamphetamine and blocked the discriminative-stimulus effects of the 1.0 mg/kg training dose of methamphetamine at doses of 5.6–10.0 mg/kg. A lower 3.0 mg/kg dose of yohimbine increased methamphetamine-appropriate responding when given together with low 0.1–0.3 mg/kg doses of methamphetamine. Conclusions:The present data suggest that the NE system plays a modulatory role in the discriminative-stimulus effects of methamphetamine. These effects appear to be mediated through NE uptake sites and alpha-2 receptors, with limited involvement of alpha-1 receptors and beta receptors.
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    Psychopharmacology 143 (1999), S. 315-317 
    ISSN: 1432-2072
    Keywords: Key words SR141716 ; Hyperphagia ; Rat ; Pre-feed ; Eating ; Appetite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Central cannabinoid systems have been implicated in appetite regulation by the respective hyperphagic actions of exogenous cannabinoids, such as Δ9-THC, and hypophagic effects of selective cannabinoid receptor antagonists. Objective: This study examined whether an endogenous cannabinoid, anandamide, could induce overeating, via a specific action at central (CB1) cannabinoid receptors. Methods: Pre-satiated male rats (n=18), received subcutaneous injections of anandamide (0.5, 1.0, 5.0, 10.0 mg/kg) before 3-h, nocturnal food intake tests. In a second series of intake tests (n=8), anandamide injection (1.0 mg/kg) was preceded by injection of the specific CB1 receptor antagonist, SR141716 (0.1, 0.5, 1.0 mg/kg SC). Results: All doses of anandamide induced significant overeating, with 1.0 mg/kg being most potent. Additionally, hyperphagia induced by 1.0 mg/kg anandamide was dose-dependently attenuated by SR141716 pretreatment. Conclusion: This first demonstration of anandamide-induced, CB1-mediated, overeating provides important evidence for the involvement of a central cannabinoid system in the normal control of eating.
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  • 89
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    Psychopharmacology 143 (1999), S. 318-321 
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Cotinine ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: The route of nicotine administration between animal models and humans is very different and further investigation by determining levels of nicotine entering into the circulatory system is warranted. Objective: The present study addresses the validity of the rat self-administration procedure by comparing plasma levels of nicotine in the rat with levels reported in smokers following cigarette consumption. Methods: Plasma levels of nicotine and its metabolite cotinine were measured in 17 rats following intravenous self-administration of a range of nicotine doses (0.015, 0.03 and 0.06 mg/kg per infusion). Results: The two larger unit doses supported reliable self-administration behaviour with no overall difference in the patterns of nicotine intake. However, the total nicotine intake over the 2-h session was related to unit dose and this correlated highly with nicotine and cotinine levels measured in blood collected from the tail vein. On average, cotinine levels (50–200 ng/ml) were approximately 2-fold higher than nicotine levels (40–120 ng/ml) in plasma. Following an extinction test for one session in which saline was substituted for nicotine, no change in behaviour was observed in the two groups, while plasma levels of nicotine and cotinine dropped to nominal levels. Conclusions: The concentrations of nicotine attained following nicotine self-administration appear to be similar to levels reported in smokers after cigarette consumption, providing further validation of this procedure as an animal model of nicotine dependence.
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  • 90
    ISSN: 1432-2072
    Keywords: Key words MDMA (3 ; 4-methylenedioxymethamphetamine) ; Serotonin ; Psychopathology ; Human ; Rat ; Prepulse inhibition ; Habituation ; Schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: Prepulse inhibition of acoustic startle refers to the reduction in the startle response when the startling stimulus is preceded by a weak prepulse stimulus. This phenomenon provides an operational measure of sensorimotor gating that has been found to be reduced in patients with schizophrenia and rats treated with serotonin agonists or serotonin releasers. Objective: In this study, we compared the effects of a serotonin releaser, MDMA, on prepulse inhibition in laboratory rats and healthy human volunteers. In particular, we investigated whether MDMA disrupts PPI in humans as observed in animal studies. Methods: Rats were tested after placebo and MDMA in a counterbalanced order at an interval of 1 week, with separate groups of rats being used for each dose of MDMA (1.7, 5.4 and 17.0 mg/kg). On each test day, rats were first tested after no injections and retested 2 h later, 10 min after a subcutaneous injection of placebo or MDMA. For the human study, a placebo-controlled within-subject design and double-blind procedures were used. Subjects were examined twice at a 2 to 4 week interval after either placebo or drug administration (order being counterbalanced). On each test day, subjects underwent baseline testing including psychological and PPI measures. Ninety minutes later, subjects received placebo or MDMA (1.7 mg/kg PO) and were retested after 75 min during the peak of behavioral effects of MDMA. Results: As expected, MDMA decreased prepulse inhibition in a dose-related fashion in rats. In contrast, a typical recreational dose of MDMA (1.7 mg/kg, orally) increased prepulse inhibition in subjects experiencing robust psychological effects. Conclusions: This surprising disparity between the effects of the drug in rats and humans may reflect a species-specific difference in the mechanism of action of MDMA or in the behavioral expression of a similar pharmacological effect, or both.
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  • 91
    ISSN: 1432-2072
    Keywords: Key words Amphetamine ; Fluoxetine ; Intracranial self-stimulation thresholds ; Withdrawal ; Depression ; Selective serotonin reuptake inhibitors ; Psychostimulant ; Reward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Withdrawal from chronic amphetamine administration is characterized by deficits in reward that resemble some symptoms of depression. Nevertheless, the effects of long-term administration and withdrawal from other drugs, such as fluoxetine, that have the potential to elevate mood in depressed individuals have not been characterized. Objectives: The purpose of this study was to characterize the effects of withdrawal from chronic amphetamine or fluoxetine administration on central reward function. Furthermore, the effects of acute or chronic pretreatment with fluoxetine on responsiveness to an acute amphetamine challenge were examined to identify potential interactions between the two drugs. Methods: A rate-independent discrete-trial threshold procedure was used to characterize self-stimulation behavior in rats prepared with bipolar electrodes in the medial forebrain bundle. Results: Elevations in intracranial self-stimulation (ICSS) thresholds, reflecting a decrease in the reward value of the stimulation, were associated with withdrawal from various chronic amphetamine treatment regimens (1–5 mg/kg, three injections per day for 1, 2, 4 or 6 days). The magnitude and duration of threshold elevations were proportional to the duration and dose of amphetamine treatment prior to withdrawal. In contrast, no alterations in ICSS thresholds were associated with withdrawal from chronic fluoxetine treatment (5 mg/kg/day for 15 days). While neither acute nor chronic administration of fluoxetine alone altered ICSS thresholds, chronic pretreatment with fluoxetine blocked the threshold-lowering effect of acute amphetamine administration (4 mg/kg), but acute pretreatment did not. Amphetamine-induced decreases in response latency, a measure of motor performance, were not affected by either chronic or acute fluoxetine pretreatment. Conclusions: The results of these experiments suggest that chronic fluoxetine treatment may induce adaptive changes in serotonergic transmission that, in themselves, do not alter the function of central reward processes, but may alter the ability of amphetamine to potentiate ICSS reward. In addition, the lack of change in ICSS thresholds during withdrawal from the chronic fluoxetine treatment regimen used suggests that withdrawal from all mood-altering drugs may not necessarily produce changes in central reward functions.
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  • 92
    ISSN: 1432-2072
    Keywords: Key words Locomotion ; Activity ; Dose-response ; Time-course ; Anticholinergic drug ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: In order to facilitate direct comparisons of anticholinergic drug effects on activity, nine drugs were tested in one laboratory using a standardized procedure. Objective: The present study compared the effects of aprophen hydrochloride, atropine sulfate, azaprophen hydrochloride, benactyzine hydrochloride, biperiden hydrochloride, diazepam, procyclidine hydrochloride, scopolamine hydrobromide, and trihexyphenidyl hydrochloride on activity levels in rats. Methods: Both fine motor activity (reflecting smaller movements) and ambulatory activity (reflecting larger movements) were recorded for 23 h following drug administration in food-restricted rats. All drugs were administered during the light period of the photocycle. Results: Atropine, azaprophen, biperiden, scopolamine, and trihexyphenidyl increased both ambulations and fine motor activity significantly during the first hour post-injection, but the increased activity levels returned to vehicle control levels within 2–6 h post-injection. Benactyzine and procyclidine only increased fine motor activity significantly above vehicle control levels and activity levels returned to vehicle control levels within 2–3 h. Finally, aprophen and diazepam generally did not increase measures of activity significantly above vehicle controls at the dose ranges examined. Conclusions: Based on potencies relative to scopolamine, the potency of the drugs could be ranked as follows: scopolamine 〉 trihexyphenidyl 〉 biperiden 〉 azaprophen 〉 procyclidine 〉 benactyzine 〉 atropine 〉 aprophen. The comparison of drug effects on activity may be useful in selecting anticholinergic drug therapies with a minimal range of side effects. In addition, these data may reduce the number of anticholinergic drugs that need to be tested in comparison studies involving more complex behavioral tests.
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  • 93
    ISSN: 1432-2072
    Keywords: Key words Dezocine ; Morphine ; 7-OH-DPAT ; Quinpirole ; SKF38393 ; SCH23390 ; Rat ; Warm-water tail-withdrawal ; Antinociception
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: The purpose of the present investigation was to evaluate the effects of the D3 agonist (±)-7-hydroxy-dipropylaminotetralin (7-OH-DPAT), various dopamine (DA) agonists and DA antagonists on the antinociceptive effects of μ opioids. Methods: Antinociception was assessed using a warm-water tail-withdrawal procedure in rats. Results: The μ opioids morphine (0.3–10 mg/kg) and dezocine (0.03–3.0 mg/kg) produced dose-dependent increases in antinociception with maximal effects obtained at the higher doses tested. Pretreatment with the putative D3 agonist 7-OH-DPAT (1.0–10 mg/kg) produced a dose-dependent attenuation of the antinociceptive effects of morphine and dezocine. At the highest dose of 7-OH-DPAT tested, the morphine dose-effect curve was shifted rightward by approximately 1.5 log units and the dezocine curve by greater than 2.3 log units. The (+)-isomer of 7-OH-DPAT (1.0 and 3.0 mg/kg) also shifted the morphine dose-effect curve to the right in a dose-dependent manner. The DA D3/D2 agonist (−)-quinpirole (0.1–10 mg/kg) attenuated the effects of morphine, but these effects were small in magnitude, not dose-dependent and observed only under a limited set of conditions. The DA D2/D3 antagonist spiperone failed to alter the morphine dose-effect curve, but reversed the effects of 7-OH-DPAT on morphine antinociception. Pretreatment with the DA D1 agonist (±)-SKF38393 (1.0 and 10 mg/kg) and the D1 antagonist (+)-SCH23390 (0.1 and 1.0 mg/kg) failed to alter the morphine dose-effect curve. Conclusion: The finding that 7-OH-DPAT markedly attenuated the effects of morphine and that these effects were reversed with spiperone suggests that activity at the D3, and possibly the D2, receptor can modulate μ agonist-induced antinociception.
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  • 94
    ISSN: 1432-2072
    Keywords: Key words Hippocampus ; Lesion ; Glutamate receptor and release ; Dopamine receptor ; Locomotor activity ; Schizophrenia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 6-week and 8-week-old rats (pre- and postpubertally) with neonatal excitotoxic lesions of the ventral hippocampus with ibotenic acid (IBO), we have studied apomorphine-induced motor activity and glutamate and dopamine D1 and D2 binding sites in the hippocampus, striatum, nc. accumbens and frontal cortex as well as K+-stimulated (3H)-D-aspartate release from hippocampal and frontal cortical slices. Specific glutamate binding was enhanced in the frontal cortex of 8-week-old IBO-treated animals, whereas that in other brain regions remained unchanged. Both D1 and D2 binding sites were downregulated in the striatum without changes in other brain structures. In 6-week-old rats, neither the glutamate nor the dopamine binding sites were altered. The amino acid release from hippocampal and frontal cortical slices of adult IBO treated rats was significantly decreased in comparison to controls, whereas in 6-week-old rats, no significant alterations were detectable. The additionally monitored motor activity was enhanced only in adult IBO-lesioned rats after apomorphine pretreatment. The present data are in agreement with the hypothesis of hyperactive dopamine and hypoactive glutamate systems in schizophrenia and are discussed in the light of schizophrenia-like behavioral changes in rats after postnatal hippocampal IBO lesion.
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  • 95
    ISSN: 1432-2072
    Keywords: Key words Cocaethylene ; Cocaine ; Alcohol ; Interaction ; Schedule-controlled responding ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Cocaethylene is a unique metabolite of cocaine, produced only in the presence of alcohol. This metabolite is pharmacologically, physiologically and behaviorally active. Further, it has been reported to interact pharmacokinetically with both cocaine and alcohol, an interaction that may mediate, in part, the interaction of cocaine and alcohol. Although cocaethylene has been shown to interact with both cocaine and alcohol, behavioral assessments of these interactions are limited. Objectives: To examine directly the behavioral interactions between cocaethylene and cocaine and between cocaethylene and alcohol, the present study assessed the effects produced by these combinations on schedule-controlled responding. Methods: Rats were first administered cumulative doses of cocaethylene, cocaine and alcohol to assess their effects alone on responding. Following this, doses of cocaethylene were combined with cumulative doses of cocaine or alcohol. Additionally, doses of cocaine or alcohol were given in combination with cumulative doses of cocaethylene. Results: When administered alone, cocaethylene, cocaine and alcohol produced dose-related decreases in responding. Further, cocaethylene shifted the dose–response functions for both cocaine and alcohol to the left and down, while cocaine and alcohol shifted the dose–response function for cocaethylene to the left and down. An isobolographic analysis revealed that these interactions were additive in nature. Conclusions: The present study suggests behavioral interactions between cocaethylene and cocaine and between cocaethylene and alcohol. The contribution of cocaethylene to the enhanced effects produced by the co-administration of cocaine and alcohol was discussed.
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  • 96
    ISSN: 1432-2072
    Keywords: Key words Ibogaine ; Cocaine ; Dose-response ; Locomotor activity ; Sensitization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Results of single-dose studies suggest that the effects of pretreatment with the putative anti-addictive compound, ibogaine, on drug-induced locomotor behavior depends on the previous drug history of the animal. Objectives: To compare the effects of ibogaine pretreatment on the dose-locomotor response function for cocaine in rats treated chronically with either saline or cocaine. Methods: Rats were chronically treated with either cocaine (15 mg/kg, IP, once daily for 5 days, followed by 2 week withdrawal) or saline. Ibogaine (40 mg/kg, IP) or vehicle was administered and 19 h later, a cocaine dose-locomotor response test was conducted (0, 5, 10, 20 and 40 mg/kg, IP). Results: Chronic cocaine administration augmented the locomotor response to cocaine in chronic cocaine-treated rats, compared to acutely treated controls. Ibogaine pretreatment enhanced the locomotor effects of cocaine in both chronic and acute cocaine groups. Furthermore, due to the shape of the dose-response curve, in chronic cocaine but not in acute cocaine rats, ibogaine pretreatment enhanced the locomotor response to 5 and 10 mg/kg cocaine while decreasing the locomotor response to 40 mg/kg cocaine. Conclusions: These data demonstrate definitively that ibogaine can enhance sensitivity to the locomotor stimulant effects of cocaine, an effect which depends, in part, on the previous cocaine history of the animal.
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  • 97
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Nornicotine ; Behavioral sensitization ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Nicotine, a tobacco alkaloid, is known to be important in the acquisition and maintenance of tobacco smoking. Nornicotine, an active nicotine metabolite, stimulates nicotinic receptors and may produce psychomotor effects similar to nicotine. Objective: The present study determined the effects of acute and repeated administration of nornicotine on locomotor activity and compared its effects with those of nicotine. Methods: R(+)-Nornicotine (0.3–10 mg/kg), S(–)-nornicotine (0.3–10 mg/kg), S(–)-nicotine (0.1–1 mg/kg) or saline was administered s.c. to rats acutely or repeatedly (eight injections at 48-h intervals). Activity was recorded for 50 min immediately after each injection. Results: S(–)-Nicotine produced transient hypoactivity, followed by dose-related hyperactivity. Repeated S(–)-nicotine administration resulted in tolerance to the hypoactivity and sensitization to the hyperactivity. Subsequent testing following a saline injection revealed evidence of conditioned hyperactivity. Acute administration of 0.3 mg/kg or 1 mg/kg R(+)- or S(–)-nornicotine produced no effect. Transient hypoactivity was observed at 3 mg/kg and 10 mg/kg R(+)-nornicotine and at 10 mg/kg S(–)-nornicotine. However, rebound hyperactivity was not observed following acute administration of either nornicotine enantiomer, suggesting that nornicotine-induced psychomotor effects differ qualitatively from those of S(–)-nicotine. Repeated R(+)-nornicotine resulted in tolerance to the transient hypoactivity, however hyperactivity was not observed. Repeated S(–)-nornicotine resulted in tolerance to the hypoactivity and the appearance of hyperactivity. Repeated administration of either nornicotine enantiomer resulted in a dose-dependent alteration in response to a 1 mg/kg S(–)-nicotine challenge, suggesting some commonalities in the mechanism of action. Conclusion: Nornicotine likely contributes to the neuropharmacological effects of nicotine and tobacco use.
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  • 98
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 146 (1999), S. 19-23 
    ISSN: 1432-2072
    Keywords: Key words Serotonin ; Sensitization ; Rat ; Dopamine opiate ; Movement disorder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Repeated high doses of morphine in the rat cause stereotypic gnawing behavior that can be re-expressed by a low dose of morphine weeks and even months after the initial treatment. The determination of the role of serotonin in this sensitized morphine-induced behavior has both empirical and theoretical relevance. Objectives: To determine whether the serotonin-reuptake blocker fluoxetine will block the development and/or the expression of this opiate-induced stereotypy. Methods: Rats were given four 10-mg/kg injections of morphine alone or with 5.0 mg/kg fluoxetine over a 36-h period. At weekly intervals for 6 weeks after the last of the sensitizing morphine doses, all rats were challenged with 4.0 mg/kg morphine. At week 2 and week 4, however, the morphine was co-administered with fluoxetine. Results: Fluoxetine completely blocked the expression of the morphine-induced stereotypy; however, when the morphine/fluoxetine-treated rats were challenged with morphine alone, they expressed similar degrees of stereotypy as the rats that initially only received morphine. Conclusions: The results indicate that increasing synaptic serotonin will block the expression but not the development of sensitization to the oral stereotypic effects of repeated high doses of morphine. Also, despite the complete blocking of the morphine effect by fluoxetine during the sensitization phase, the presence of significant biting by these rats during the challenge with morphine alone argues that conditioning factors are not a necessary component for the morphine sensitization to develop.
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  • 99
    ISSN: 1432-2072
    Keywords: Key words Delayed non-matching to position task ; Scopolamine ; ENA 713 ; Exelon ; Working memory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: The disruption of working memory in the delayed non-matching to position (DNMTP) task by the muscarinic antagonist, scopolamine, is considered to be a model of the spatial working memory deficit in Alzheimer’s disease (AD) patients. Objective: To investigate whether ENA 713 (Exelon) (0.1, 0.5 mg/kg, IP), an acetylcholinesterase inhibitor, would reverse the effects of scopolamine in the DNMTP task. Methods: Male Lister Hooded rats were trained to criterion in an operant DNMTP task (0- to 16-s delay intervals) before receiving vehicle, scopolamine (0.05 mg/kg, SC) alone, ENA 713 (0.1, 0.5 mg/kg, IP) alone, or combinations of scopolamine and ENA 713, in two variations of the task – with and without barriers inserted between the food magazine and the two levers. Barriers were inserted to prevent the use of positional strategies to perform the task, since this behaviour may confound the conclusions of the effect of drugs on working memory. Results: It was found that: (i) scopolamine significantly reduced choice accuracy delay-dependently in both test situations while modifying non-mnemonic measures of task performance delay-independently, indicating an impairment of working memory; (ii) ENA 713 (0.5 mg/kg) significantly attenuated the scopolamine-induced impairment of working memory and significantly reduced the scopolamine-induced changes in some non-mnemonic measures of task performance; (iii) the presence of barriers did not alter the effects of scopolamine and ENA 713 on working memory. Conclusion: ENA 713 reversed the working memory deficit induced by scopolamine. These results are consistent with the attenuation of learning and memory disruptions due to cholinergic dysfunction by ENA 713 in other preclinical assays, and predict a drug-induced improvement in working memory in AD patients.
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  • 100
    ISSN: 1432-2072
    Keywords: Key words Dextromethorphan ; Dextrorphan ; Phencyclidine ; Self-administration ; Drug discrimination ; Monkey ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Dextromethorphan (DXM) and its metabolite, dextrorphan (DXO) have neuroprotective and anticonvulsant properties through their activity as N-methyl-d-aspartate (NMDA) receptor channel blockers. Based on this receptor activity, coupled with reports of DXM abuse, both were evaluated for abuse potential and phencyclidine (PCP)-like behavioral effects in two animal models. Objectives and methods: The discriminative stimulus properties of DXO and DXM were tested in rats (3–56 mg/kg DXM, i.p. and 2.2–40.9 mg/kg DXO, i.p.) and rhesus monkeys (0.3–10 mg/kg DXM, i.m. and 0.25–8.0 mg/kg DXO, i.m.) trained to discriminate PCP from saline using a standard two-lever drug-discrimination paradigm under a fixed-ratio (FR) schedule of food reinforcement. In a second set of experiments, i.v. self-administration of DXO (10–100 µg/kg/infusion) and DXM (10–1000 µg/kg/infusion) were tested under a FR schedule of reinforcement in monkeys trained to lever press for infusions of PCP during daily 1-h sessions. Results: In rats, both DXM and DXO produced a dose-dependent substitution for PCP. When tested in monkeys, DXM yielded partial (1 monkey) and full (2 monkeys) substitution for PCP, while DXO substituted fully for PCP in all four subjects tested. In the self-administration study, in five of the six subjects, at least one dose of DXM served as a positive reinforcer, maintaining infusion rates above those for saline. For DXO, at least one dose maintained infusion numbers well above mean saline infusion numbers in all subjects. Conclusions: Taken together, these data show that DXM has some PCP-like effects in rats and monkeys, but that they are more reliably produced by its metabolite, DXO. Thus, high doses of DXM may have some PCP-like abuse potential in humans but this potential may be associated with, or enhanced by, metabolism of DXM to DXO.
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