L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant patients

BACKGROUND: Cyclosporin has been shown to facilitate renal vasoconstriction and to have an antinatriuretic effect. The existence of an interference of cyclosporin with the vasodilating properties of endothelium mediated by nitric oxide production could mediate these effects. On the other hand, the infusion of the nitric oxide precursor L-arginine has been shown to induce renal vasodilatation and to facilitate natriuresis in normal volunteers. We have investigated the renal effects of the administration of an infusion of L-arginine in renal transplant patients chronically treated with cyclosporin. To facilitate the analysis of the data the effects of the administration of a similar dose of cyclosporin on renal function during the infusion of a vehicle were also investigated during the administration of a vehicle of L-arginine. DESIGN: Ten male renal transplant patients, chronically treated with cyclosporin and with a stable renal function were studied during 2 consecutive days after the administration of the usual morning dose of cyclosporin. The first day they received an intravenous infusion of vehicle and the second the infusion of graded doses of L-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h. RESULTS: The first day, after cyclosporin administration a significant fall (P < 0.01) was observed in natriuresis and kaliuresis in the absence of changes in renal plasma flow and glomerular filtration rate. After the administration of L-arginine significant (P < 0.01) increases of renal plasma flow, glomerular filtration rate, and natriuresis were seen. The increase in blood levels of cyclosporin after its administration did not differ between days 1 and 2. CONCLUSION: These results indicate that L-arginine facilitates renal vasodilatation and natriuresis in renal transplant patients. Furthermore, the observed increase in sodium excretion could indicate that L-arginine counteracts the antinatriuretic effect of cyclosporin.      

An unusual clinical presentation of bilateral schizencephaly

Summary We present a case with a characteristic magnetic resonance image (MRI) of bilateral open-lipped schizencephaly and atypical clinical presentation. The patient is still alive and in good health in her forties, she has never presented seizures, and although the motor dysfunction is well correlated with cerebral lobe involvement, neurobehavioral dysfunction is not proportional to the MR image of the cerebral malformation.

---

Un cas inhabituel de schizencéphalie bilatérale

Résumé Nous présentons un cas de schizencéphalie bilatérale ouverte caractérisé par une présentation clinique atypique et une imagerie par résonance magnétique nucléaire caractéristique. La patiente est encore vivante, en bonne santé, à plus de 40 ans, elle n'a jamais présenté de crise comitiale et, bien que les troubles moteurs soient bien corrélés aux altérations cérébrales, les troubles neuro-comportementaux ne sont pas proportionnels aux images IRM de cette malformation cérébrale.

     

Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases

Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative diseases resulting from the inability to catabolize GM2 ganglioside by beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit (Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B (beta beta homodimer) is also defective in Sandhoff disease. We previously developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs) mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff) mice succumb to a profound neurodegenerative disease by 4-6 months of age. Here we find that neuron death in Hexb-/- mice is associated with apoptosis occurring throughout the CNS, while Hexa-/- mice were minimally involved at the same age. Studies of autopsy samples of brain and spinal cord from human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances, in keeping with the severe expression of both diseases. We suggest that neuron death is caused by unscheduled apoptosis, implicating accumulated GM2 ganglioside or a derivative in triggering of the apoptotic cascade.      

Anatomic bases for liver transplantation

Summary This study gathers the anatomic implications for a good liver transplantation. During hepatic removal a left hepatic a.exists in 20% of cases; a right hepatic artery originating from the superior mesenteric a. (SMA) can be the only arterial supply in 9% of cases; the whole lesser omentum has to be removed and the SMA from 6 cm to its origin. The SMA must be freed from the celiac ganglia and its ostium removed with the celiac trunk in an aortic patch cut on the anterior side in order to avoid the renal ostia. During total hepatectomy, dissection of the portal triad is often difficult because of portal hypertension dilating accessory portal veins (parabiliary arcade) and pedicular lymphatics. Nerve plexuses are thick in front of the hepatic artery or behind the portal triad. Transection of triangular ligaments leads to the retrohepatic inferior vena cava (IVC) that must be freed from its posterior tributaries (right suprarenal vein and inferior phrenic veins flowing either into the IVC or into the hepatic veins). One big problem during hepatic replacement is the biliary anastomosis which must be well irrigated. In the recipient, dissection up to the hilum preserves hepatic and pancreatico-duodenal pedicles. The biliary tract of the graft must be cut low, behind the pancreas, and several centimeters of the gastroduodenal artery must be preserved to save hepatic and gastroduodenal pedicles.

---

Bases anatomiques de la transplantation hépatique

Résumé Ce travail rassemble les notions anatomiques nécessaires au bon déroulement d'une transplantation hépatique. Le prélèvement du greffon doit enlever tout le petit omentum contenant une éventuelle a. hépatique gauche née de l'a. gastrique gauche (20%) et emporter l'a. mésentérique supérieure jusqu'à 6 cm de son origine pour ne pas oublier une a. hépatique droite née de cette dernière: son ostium est pris avec le tronc clique dans un patch aortique découpé sur la face antérieure. Lors de l'hépatectomie totale, la dissection du pédicule hépatique est rendue délicate par l'hypertension portale qui dilate les veines portes diets accessoires (arcade parabiliaire) et les lymphatiques pédiculaires. Les plexus nerveux sont riches devant l'artère hépatique et derrière le pédicule. La section des ligaments triangulaires droit et gauche amène à la veine cave inférieure (VCI) rétro-hépatique qu'il faut libérer de ses afférences postérieures (en particulier la veine surrénale principale droite toujours haut située et les veines phréniques inférieures qui s'abouchent soit dans la VCI soit dans les veines hépatiques du carrefour). Lors du remplacement, l'anastomose biliaire doit être vascularisée. Chez le receveur la dissection jusqu'au hile permet de conserver les pédicules. La voie biliaire du greffon doit être coupée bas derrière le pancréas et les premiers centimètres de l'artère gastro-duodénale conservés pour préserver les pédicules hépatique et pancréaticoduodénal.

     

The scope for preventive medicine in general practice in the East End

Primary care is seen as an obvious setting for preventive programmes, but a number of studies present a negative view of inner city primary care, with criticism directed particularly at older single-handed GPs. This may not be justified. A survey of 56 of the 84 GPs in the inner London borough of Tower Hamlets, found a higher than average proportion of single-handed GPs over 60 and a high level of dissatisfaction with premises. Half said they carried out some kind of preventive programme, usually hypertension screening, and three quarters were interested in doing so. Only one practice had a patient support group, but 70 per cent thought they were a good idea. Given support and help, more GPs would consider preventive programmes and set up patient support groups.     

Cadmium and zinc accumulation and elimination by freshwater crayfish

A theoretical compartment model for the uptake of Cd and Zn by the freshwater crayfish,Procambarus acutus acutus (Girard), was constructed, and included a factorially designed experiment to study the relative importance of food and water as uptake vectors for¹⁰⁹Cd and⁶⁵Zn. Food and water were important pathways for Cd accumulation and the two uptake vectors were first order, independent, and additive. The rate of Cd elimination was not significantly different from zero during either the uptake or depuration phases. Rate constants for uptake from 5 and 10 g Cd · L^–1, calculated on a concentration basis, were 0.84 ± 0.031 and 0.83 ± 0.029 day^–1, respectively. Although there was no measurable Cd elimination, crayfish reached a steady state concentration of about 12.5g Cd · g^–1, dry weight. A small amount of Zn was accumulated via food, relative to that accumulated from water; the former had a much longer retention time than the latter, which was lost rapidly. When Zn in food was the only source, steady state was reached rapidly; Zn accumulation from food and water was not additive. Zn accumulated from water, reached no steady state. Zn uptake was proportional to water concentrations within the fed treatment groups and those not fed Zn-contaminated food. Zn elimination was first order to Zn concentration in the crayfish. Rate constants for Zn accumulation from 50 and 100 g Zn · L^–1 when fed Zn-contaminated food were 1.34 ± 0.064 and 1.46 ± 0.073 day^–1 (estimate ± 95% CI based on concentration), respectively, while rate constants for Zn elimination were 0.034 ±0.0021 and 0.05 ± 0.0032, respectively.     

Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen

Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age. However, TAM therapy has been shown to result in an increased incidence of endometrial carcinoma in women. The present study was designed to investigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g. to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on their female offspring. Progressive proliferative hyperplasia of the oviduct was frequently seen in TAM-exposed offspring, reaching 100% incidence by 52 weeks in both treatment groups. These females also developed progressive proliferative uterine lesions, including moderate/severe cystic endometrial hyperplasia (34-50%) and polypoid adenomas (27-30%) between 53 and 78 weeks. Deciduomas (15%) occurred at young ages (12 and 24 weeks) while leiomyomas (14%), a malignant leiomyosarcoma, and ovarian granulosa cell tumors (14%), were found between 72 and 78 weeks. Our findings thus suggest a strong association between transplacental TAM and reproductive tract abnormalities in female CD-1 mice.