Hepatic failure associated with imipramine therapy

Imipramine, a widely used antidepressant, has rarely been associated with hepatic abnormalities. In the majority of reported cases, hepatic effects have been transient and readily reversible on discontinuation of the drug. We cared for an 11-year-old boy with hepatic failure and massive cell necrosis which followed treatment with imipramine for enuresis. This therapy led to fulminant hepatic failure and subsequent liver transplantation.     

Effect of streptozocin-induced diabetes on insulin-receptor tyrosine kinase activity in obese Zucker rats

We examined insulin binding, insulin-stimulated autophosphorylation, and phosphorylation of poly(Glu.Na,Tyr)4:1 by liver and skeletal muscle insulin receptor from lean, obese, and obese streptozocin-induced diabetic Zucker rats. Induction of diabetes with streptozocin (30 mg/kg) lowered the lasting insulin level from 11.4 to 3.8 ng/ml, which was not significantly greater than the lean control level. Autophosphorylation and tyrosine kinase activity of liver insulin receptors were increased 70-100% in the obese control group (relative to lean rats), but diabetes reversed this hyperresponsiveness to insulin. In muscle, obesity was associated with a 40-50% decrease in autophosphorylation and tyrosine kinase activity, which was also reversed in the diabetic state. Autophosphorylation and tyrosine kinase activity were significantly correlated in liver and muscle and were also correlated with fasting insulin levels. These data suggest that insulin-receptor tyrosine kinase activity is regulated differently in liver and muscle and that the abnormalities in kinase activity associated with the obese Zucker rat are at least partly secondary to hyperinsulinemia.     

Dilation of the ventriculus terminalis: sonographic findings.

A newborn term male infant was found to have the stigmata of VACTERL syndrome, including cervical and thoracic hemivertebra, partial sacral agenesis, 13 pairs of ribs, high imperforate anus with rectovesical fistula, and tracheoesophageal fistula with proximal esophageal atresia. No open spinal dysraphism or skin dimpling was seen. Ultrasonography of the spinal cord was performed to screen for occult anomalies. The examination revealed a lipoma of the filum terminalis and a low-lying conus medullaris at the L3-L4 level with a large central cystic structure in the terminal cord, which was continuous with the central canal (Fig. 1). This was thought to most likely represent a dilated ventriculus terminalis, and the diagnosis was confirmed on a subsequent MR image (Fig. 2). Fluid in the cyst followed cerebrospinal fluid signal in all sequences. We observed no abnormal signal in the adjacent parenchyma or enhancement associated with the cystic mass. A cranial ultrasonogram did not reveal any intracranial anomalies. The patient demonstrated no neurologic deficits in the lower extremities. Bowel and urinary continence was not assessable in this infant.     

Tooth wear and occlusal sounds. Comparative study of restorative and orthodontic indices. Preliminary report

A comparative study of dental arch forms was conducted according to their manifestation of relative tooth wear and occlusal sounds. Thirty-six subjects were grouped according to their dental treatment experience into one of five arch form categories. Significant differences in the severity of tooth wear were found between the five groups. Tooth sounds were also found to be related to the dental arch form, and thus dental treatment category.     

Results of Medical Research Council Childhood Leukaemia Trial UKALL VIII (Report to the Medical Research Council on behalf of the Working Party on Leukaemia in Childhood)

During the 1970s, despite apparently similar treatment, the prognosis for children with lymphoblastic leukaemia (ALL) improved more in some countries, notably the United States and West Germany, than in others. To find out why, the first phase of the United Kingdom (UK) Medical Research Council (MRC) childhood ALL trial, UKALL VIII, was designed to see whether similar results to the United States Children's Cancer Study Group (CCSG) could be obtained in the U.K. using an identical protocol (CCG 162). Protocol 162 was one of a series of regimens devised by the American Children's Cancer Study Group in the 1970s and was used specifically for their average risk patients (all children with ALL with an initial white cell count up to 50 x 10(9)/l except those aged 3-6 years with white cell counts under 10 x 10(9)/l). One arm (1A) of their study was adopted by the MRC for all children in the U.K. aged 0-14 years with confirmed ALL. Eight hundred and twenty-nine consecutive patients were entered between 1980 and 1984. The first 199 patients formed a single arm study as per the original protocol 162 (arm 1A), but the subsequent 630 children were randomized to receive or not two doses of daunorubicin on the first 2 d of induction. This randomization was an attempt to answer the important question as to whether event-free survival was influenced by the use of four rather than three induction agents. A second randomization between 2 and 3 years continuing therapy was also introduced at this stage as it had been by the CCSG in their protocol. With a minimum follow up period of more than 5 years, disease-free survival for the whole group is 55%, a considerable improvement on all previous UKALL trials. Results for patients directly comparable with those in CCSG 162 ('average risk' patients) and their American counterparts were similar. Daunorubicin was associated with more early deaths but improved disease-free survival for those achieving remission. More children relapsed who stopped treatment after 2 years than those who continued for 3, but this was balanced by increased treatment mortality in the third year. The fact that for UKALL VIII the results were similar to those of the CCSG suggests that previous MRC protocols were not sufficiently sustained and intensive, particularly during the maintenance phase of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)     

Are general practitioner hospitals cost-saving? Evidence from a rural area of Norway

OBJECTIVE: We aimed to determine whether general practitioner GP hospitals, compared with alternative modes of health care, are cost- saving. METHODS: Based on a study of admissions (n = 415) to fifteen GP hospitals in the Finnmark county of Norway during 8 weeks in 1992, a full 1-year patient throughput in GP hospitals was estimated. The alternative modes of care (general hospital, nursing home or home care) were based on assessments by the GPs handling the individual patients. The funds transferred to finance GP hospitals were taken as the cost of GP hospitals, while the cost of alternative care was based on municipality and hospital accounts, and standard charges for patient transport. RESULTS: The estimated total annual operating cost of GP hospitals was 32.2 million NOK (10 NOK = 1 Pound) while the cost of alternative care was in total 35.9 million NOK. Sensitivity analyses, under a range of assumptions, indicate that GP care in hospitals incurs the lowest costs to society. CONCLUSION: GP hospitals are likely to provide health care at lower costs than alternative modes of care.      

Immunoregulatory markers in rats carrying Dunning R3327 H, G, or MAT-LyLu prostatic adenocarcinoma variants

The Dunning R3327 tumor represents a system for studying prostate cancer in Copenhagen X Fischer rats. Animals bearing variant sublines (H, G, and MAT-LyLu) differing in growth rate, differentiation, hormone responsiveness, and metastatic ability were assayed for three immunological markers. Spleens were passed through a tissue sieve, and mononuclear cells were obtained by Ficoll-Hypaque centrifugation. These were assayed for leukocytic subsets using monoclonal antibodies. An adherent population was isolated and evaluated using thin-layer chromatography for conversion of radiolabeled arachidonic acid to E series prostaglandins. Finally, sera from these animals were assayed for levels of circulating immune complexes using polyethylene glycol precipitation. Data from 52 rats bearing the various tumors were obtained, correlated with subline aggressiveness, and compared to 15 controls. Each tumor group demonstrated significantly lower helper/suppressor T-cell ratios than controls, probably due to general tumor presence. In addition, the most aggressive R3327 MAT-LyLu variant had significantly increased prostaglandin E synthesis by adherent spleen cells compared to the H or G sublines and significantly increased levels of circulating immune complexes relative to the H subline. G subline values for both prostaglandin E and circulating immune complexes levels were intermediate, suggesting that these markers correlate better with tumor aggressiveness than helper/suppressor T-cell ratios.     

Determinations of glucose turnover and oxidation in normal volunteers and septic patients using stable and radio-isotopes: the response to glucose infusion and total parenteral feeding

Rates of glucose turnover and oxidation were isotopically determined in normal volunteers (n = 16) and in severely septic patients (n = 10). Glucose turnover was determined using primed constant infusions of either 6-3H- or 6,6-d-glucose and glucose oxidation with either U-14C-glucose or U-13C-glucose after appropriate priming of the bicarbonate pool. Basal rates of glucose turnover, oxidation, and plasma clearance were significantly higher in the septic patients than in the volunteers. During glucose infusion (4 mg/kg.min) endogenous glucose production was virtually abolished in the volunteers (94 +/- 4% suppression). There was significantly less suppression in the septic patients (39 +/- 7%); (P less than 0.01). In addition, the percentage of available glucose oxidized (i.e. the percentage of glucose uptake oxidized) was significantly less in the septic patients. When the patients were studied during total parenteral nutrition (at a similar rate of glucose infusion) there was no further suppression of endogenous glucose production compared with that seen during 2 h of glucose infusion. However, the percentage of available glucose oxidized increased significantly. From these studies it is concluded that septic patients continue to have ongoing consumption of host tissue despite receiving either glucose infusion or total parenteral nutrition, and septic patients are less able to oxidize glucose than normal volunteers when infused for only 2 h. However, adaptation occurs with the longer infusion time used in total parenteral nutrition (TPN).