Familial Juvenile Nephronophthisis in Two Siblings — Histological Findings at an Early Stage —

We present two female siblings with familial juvenile nephronophthisis (FJN) which was diagnosed at the early stage of renal failure. Diagnosis was made during the investigation of anemia in case 1 and by a subsequent family survey in case 2. Most patients with FJN are not identified until the terminal stage of renal failure and such cases have rarely been reported in Japan. Case 2 had a reduction in the maximum urinary concentration ability but no azotemia, and among the FJN patients reported in Japan so far she has the least advanced renal disease. Histological examination of the renal biopsy in case 1 showed typical findings of FJN, such as thickening and lamination of the tubular basement membrane (TBM), interstitial fibrosis, and round cell infiltration of the interstitium. In case 2, renal biopsy revealed an irregular marked thickening of the TBM with trivial interstitial changes and a normal glomerular appearance. The histology of these two cases suggests that the TBM may be the primary site affected in FJN.     

Fulminant childhood hemophagocytic syndrome mimicking histiocytic medullary reticulosis. An atypical form of Epstein-Barr virus infection.

Ten cases of pediatric fulminant hemophagocytic syndrome, encountered between 1986 and 1989, are described. They occurred in the summer, and the patients presented with fever, jaundice, hepatosplenomegaly, pancytopenia, coagulopathy, and abnormal liver function. Bone marrow studies revealed infiltration by atypical T-lymphoid cells, rare B immunoblasts, and mature histiocytes with hemophagocytosis. Initially, histiocytic medullary reticulosis was suspected in six cases. The clinical course was characterized by rapid deterioration, with a mean period of 16 days from onset of fever to death. The main causes of death were coagulopathy with multiple organ failure and opportunistic infection. In seven of eight cases studied by serologic assay and Southern blot hybridization, acute or active Epstein-Barr virus (EBV) infection was documented. It is suggested that an atypical or fulminant form of primary EBV infection distinct from classic infectious mononucleosis was prevalent in previously healthy children in Taiwan. Younger age involvement and seasonal clustering were characteristic of the disorder described.     

Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.     

Single- and multiple-dose pharmacokinetics of ceftazidime in infected patients with varying degrees of renal function

To determine the single- and multiple-dose ceftazidime kinetics, we administered ceftazidime, 2 gm intravenous bolus every 12 hours, to 14 infected Chinese patients with various degrees of renal function. Blood samples were drawn in serial after the first and 7th dose and serum ceftazidime concentrations were measured by high pressure liquid chromatography. Ceftazidime concentration-time data were fitted to a two-compartment model with a nonlinear regression program. Ceftazidime kinetics was unaltered by repeated dosing. Both total body clearance and elimination rate constant of ceftazidime decrease significantly in proportion to the creatinine clearance estimated by Bjornsson's method. Renal insufficiency did not modify the steady-state volume of distribution (Vdss) of ceftazidime which, however, appeared to be larger than those reported previously. This larger Vdss may be explained by acute infection process, confinement to bed, and increased extracellular fluid volume as a result of hypoalbuminemia. Our study indicates the estimated creatinine clearance as a useful guide to ceftazidime dosage adjustment and also emphasizes the clinical relevance of conducting kinetic studies of antibiotics in infected patients.     

Relative and absolute bioavailability of cibenzoline capsules and tablets in healthy subjects

Eighteen healthy adult volunteers completed an open-label, four-way crossover study designed to determine the bioequivalency of 160-mg cibenzoline [2-(2,2-diphenylcyclopropyl)-4,5-dihydro-1H-imidazole] capsules and tablets, their relative bioavailability compared with an oral solution of the drug, as well as the absolute bioavailability of these dosage forms compared with an intravenous infusion of the drug. Blood samples obtained at specified times after drug administration were assayed for cibenzoline by HPLC, and pharmacokinetic parameters were estimated from the resulting plasma concentration-time profiles. Comparisons were made between the tablet and capsule to assess bioequivalency, between the solid dosage forms and a solution to assess relative bioavailability, and between the oral forms and an intravenous infusion to assess absolute bioavailability. The pharmacokinetic parameters for each oral dosage form were similar and ratios of mean parameters indicated that the solid dosage forms were bioequivalent and completely bioavailable relative to an oral solution. The ratios of the area under the plasma concentration-time profiles (AUC) for the capsule, tablet, and oral solution to that of the intravenous infusion were 0.85, 0.83, and 0.86, respectively, indicating that orally administered cibenzoline has an absolute bioavailability of approximately 85%.     

Role of Alcohol-induced Hypothermia in Mediating the Teratogenic Effects of Alcohol in C57BL/6 J Mice

The purpose of this study was to determine the role of alcohol-induced maternal hypothermia in the teratogenic actions of alcohol. C57BL/6J mice were administered an acute dose of alcohol (5.8 g/kg orally) or isocaloric sucrose on day 10 of gestation. One half of each group was placed for 6 hr in an incubator set at 32 degrees C and the other half was housed in the incubator at room temperature (22 degrees C). As expected, acute prenatal alcohol exposure at this time of gestation was associated with decreased birth weight and an increase in limb and kidney malformations. The significant alcohol x environmental temperature interaction on these dependent variables indicated that the teratogenic insult was not attenuated, but was in fact even greater for the 32 degrees C/alcohol group. An absence of a main effect of environmental temperature indicated that the 32 degrees C environment, per se, was not teratogenic. Thus, maternal hypothermia is probably not an etiological factor in animal models of fetal alcohol syndrome. Moreover, antagonism of alcohol-induced maternal hypothermia exacerbates the teratogenic actions of alcohol observed at room temperature.     

Psychiatric rehabilitation in a French-speaking setting: current practices, future challenges]

This paper aims to assess current interventions in psychiatric rehabilitation in the French-speaking world and to discuss future developments. We review examples of policies and practices in Quebec and Europe and discuss the role and involvement of professionals; namely, the psychiatrists and the nursing staff. We also present different rehabilitation strategies and techniques used in the French-speaking world, such as case management, social-skills training, cognitive therapies for psychotic symptoms, family interventions, and return-to-work interventions. In conclusion, we invite psychiatrists to play a more active role in rehabilitation. We recommend the creation of small, specialized units closely linked to the needs of clients, and we propose to integrate social and medical interventions, rather than opposing them.     

Metastatic septic endophthalmitis in pyogenic liver abscess

In a consecutive series of 180 patients with pyogenic liver abscess, three patients (two men and one woman, between 46 and 75 years of age) had metastatic Klebsiella endophthalmitis. The incidence of metastatic endophthalmitis was 1.7% in patients with pyogenic liver abscess, 5.2% in patients with Klebsiella liver abscess, and 7.8% in patients with Klebsiella liver abscess having Klebsiella bacteremia. Despite aggressive therapeutic measures, the men permanently lost their vision and the woman eventually required an evisceration of her right eye. Delayed recognition and/or treatment as well as the nature of bacteria probably contributed to the tragic outcome. The findings suggest that a high index of suspicion is critical and a combined effort of the internist and ophthalmologist is mandatory.