Interaction of thiamine deficiency and voluntary alcohol consumption disrupts rat corpus callosum ultrastructure.

The relative roles of alcohol and thiamine deficiency in causing brain damage remain controversial in alcoholics without the Wernicke-Korsakoff syndrome. Experimental control over alcohol consumption and diet are impossible in humans but can be accomplished in animal models. This experiment was designed to differentiate the separate and combined effects on the macro- and ultrastructure of the corpus callosum of thiamine deficiency and voluntary alcohol consumption. Adult male alcohol-preferring (P) rats (9 chronically alcohol-exposed and 9 water controls) received a thiamine-deficient diet for 2 weeks. There were four groups: five rats previously exposed to alcohol were treated with pyrithiamine (a thiamine phosphorylation inhibitor); five rats never exposed to alcohol were treated with pyrithiamine; four alcohol-exposed rats were treated with thiamine; and four rats never exposed to alcohol were treated with thiamine. On day 14, thiamine was restored in all 18 rats; 2 weeks later the 10 pyrithiamine-treated rats received intraperitoneal thiamine. The rats were perfused 61 days post-pyrithiamine treatment at age 598 days. Brains were dissected and weight and volumes were calculated. Sagittal sections were stained to measure white matter structures. The corpus callosum was examined using transmission electron microscopy to determine density of myelinated fibers, fiber diameter, and myelin thickness. The corpus callosum in the alcohol/pyrithiamine group was significantly thinner, had greater fiber density, higher percentage of small fibers, and myelin thinning than in the alcohol/thiamine and water/thiamine groups. Several measures showed a graded effect, where the alcohol/pyrithiamine group had greater pathology than the water/pyrithiamine group, which had greater pathology than the two thiamine-replete groups. Across all 16 rats, thinner myelin sheaths correlated with higher percentage of small fibers. Myelin thickness and axon diameter together accounted for 71% of the variance associated with percentage of small fibers. Significant abnormalities in the alcohol/pyrithiamine group and lack of abnormality in the alcohol-exposed/thiamine-replete group indicate that thiamine deficiency caused white matter damage. The graded abnormalities across the dually to singly treated animals support a compounding effect of alcohol exposure and thiamine depletion, and indicate the potential for interaction between alcohol and thiamine deficiency in human alcohol-related brain damage.     

Complications occurring during conservative management of splenic trauma in children.

AIM: Conservative management of splenic rupture in haemodynamically stable children is now generally accepted. However, during follow-up, many complications can occur. The aim of this study was to describe the complications we observed and to propose a standardised follow-up adapted to them. METHODS: Between March 1992 and December 2002 we managed 65 children (aged between 3 and 15 years old) with accidental splenic rupture. Follow-up and treatment consisted of a 10-day bed rest with sonogram and Doppler controls on the 5th and 10th day and subsequently every month until complete healing. Complications included secondary haemorrhage in 3 cases, cystic evolution in 5 cases, and pseudo-aneurysm in 2 cases. All were treated by renewed bed rest. Three of the cysts resolved spontaneously, the other two underwent cystic resection and epiploplasty by laparotomy (n = 1) or laparoscopy (n = 1) and both pseudo-aneurysms were selectively embolised. There were no splenectomies. CONCLUSIONS: Complications essentially occurred in older children and were not related to gender, type of fracture, or extent of bleeding. Cystic evolution of the sub-capsular haematomas can appear up to 1 month after trauma. Peripheral pseudo-aneurysms which could be responsible for secondary haemorrhages were selectively embolised. We favour the use of the Doppler sonogram for follow-up until total recovery of these patients, even in low-grade traumas. Considering the number of complications encountered we do not believe the American evidence-based guidelines are suitable for our population.     

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.      

Phase II trials of rhizoxin in advanced ovarian, colorectal and renal cancer.

Rhizoxin is a tubulin-binding anti-neoplastic agent which is active in a range of murine tumour models. The recommended schedule, of intravenous (i.v.) bolus administration at a dose of 2 mg m-2 every 3 weeks, has been assessed in three phase II trials of ovarian, renal and colorectal cancer. In general terms the drug was fairly well tolerated, but the response rate was disappointing: 0/18, colorectal cancer; 0/18, renal cancer; 1 partial response (PR)/17, ovarian cancer.     

Occupational health aspects of the arsenic extractive industry in Britain (1868-1925).

A historical survey into the occupational hazards of mining and refining arsenic is presented together with the measures adopted for their control. The industry is placed in the social perspective of its time and it is suggested that this experience could be of value to those who may encounter similar problems where arsenic is extracted elsewhere in the world.     

The parapelvic renal cyst. A rare aetiology of blood hypertension in children.

Parapelvic renal cysts are uncommon in children. We report a case occurring in a 2-year-old girl, diagnosed during follow-up for blood hypertension. The cyst measured 8 cm in length. There was associated hydronephrosis, due to obstruction of the renal pelvis. Surgical resection was performed. Normotension returned within 3 months, and the obstruction disappeared. A renovascular mechanism can be evoked to explain hypertension.     

Predictive testing for Huntington's disease: I. Predictors of uptake in South Wales

In Wales, predictive testing for Huntington's disease (HD) has not been offered proactively to families and uptake of testing is low in comparison to other centres. Little is known of those not requesting testing, particularly those not in direct contact with the genetics service. This study examined differences between a cohort of 22 test applicants and a random group of 32 'non-requesters', drawn from the South Wales HD register. Respondents were interviewed by means of a semi-structured schedule in their own homes. The study groups differed significantly on a number of variables including: knowledge of the availability of testing; perceived attitudes of family members and significant others to testing; length of knowledge and perceived stressfulness of being at risk; and perceived ability to cope with an unfavourable result. Overall, knowledge of testing procedures was poor and at-risk individuals' understanding of genetic terminology was at odds with scientific distinctions. Discussion focuses on the organisational and psychological factors associated with lack of knowledge of the availability of testing and the interpretation of reported coping capacities.