Reversal of diabetes in BB rats by transplantation of encapsulated pancreatic islets

Prolonged survival of pancreatic islet allografts implanted in diabetic BB rats was achieved by encapsulation of individual islets in a protective biocompatible alginate-polylysine-alginate membrane without immunosuppression. Intraperitoneal transplantation of the encapsulated islets reversed the diabetic state of the recipients within 3 days and maintained normoglycemia for 190 days. Normal body weight and urine volume were maintained during this period, and no cataracts were detected in the transplant recipients. In contrast, control rats receiving transplants of unencapsulated islets experienced normoglycemia for less than 2 wk. These results demonstrated that microencapsulation can protect allografted islets from both graft rejection and autoimmune destruction without immunosuppression in an animal model that mimics human insulin-dependent diabetes.     

Detection of undiagnosed coagulopathies using routine rapid heparin neutralization.

OBJECTIVE: To determine the most frequent clinical causes of a prolonged activated partial thromboplastin time (APTT) result, and to determine whether a new heparin-removal device (the Hepchek, Pall Biomedical, Glen Cove, NY 11542) is capable of efficiently detecting the causes of these values. DESIGN: A combination of chart review and laboratory testing comparing the criterion standard--the heparin chromogenic substrate assay--with the Hepchek. Laboratory investigations were blinded and controlled. SETTING: Inpatient, acute-care hospital. PATIENTS: A total of 1,000 hospital patients with a variety of hemostatic disorders. MAIN OUTCOME MEASURE: The extent to which the Hepchek accurately identified the etiology of a prolonged APTT result. RESULTS: The APTT was prolonged in 25.2% of samples. The presence of heparin in the sample was confirmed by chromogenic assay or by using the Hepchek heparin-removal filter. The presence of heparin was confirmed in 12.8% of all samples and in more than 50% of all abnormal samples. The cause of the abnormal APTT was often unappreciated by the clinician. Bayesian analysis of the Hepchek's ability to diagnose heparin correctly as the cause of the abnormal APTT showed a sensitivity of 100% and specificity of 99.9%. CONCLUSION: Use of the Hepchek in the routine clinical laboratory is an efficient and rapid method of detecting heparin as a cause of isolated prolonged APTT results, and should reduce demands for unwarranted coagulation analyses and inappropriate treatment with blood products.     

Guillain-Barré syndrome in South-West Stockholm, 1973–1991, 3. Clinicoepidemiological subgroups

Using hierarchical cluster analysis, applied to 47 cases of Guillain-Barre Syndrome (GBS) incident in South-West Stockholm (SWS) during the period from January 1973 to June 1992, we identified three major clinicoepidemiological subgroups. The first subgroup, 25.5% of the cases (26.7 ± 6.7 years), recorded a peak incidence at ages 20–29 years and presented significant differences from other subgroups, a high proportion of cases with onset at low age preceded by respiratory infection (83.3%) and with normal motor conduction velocity (50.0%). Also found, were less affected biological parameters, a rapidly progressive course and independence in gait at one month after onset. A second subgroup, 27.7% of cases, was severely affected, clinically and functionally. It consisted predominantly of young individuals (22.7 ± 11.1 years), with a high incidence (69.2% of cases) in autumn. A third subgroup, comprising 40.47; of cases, was older (61.1 ± 11.0 years) and, in general, also severely affected. The incidence of this form appeared to be invariant with time.     

CT- or sonography-guided biopsy of the liver in the presence of ascites: frequency of complications

The presence of ascites has been considered a contraindication to percutaneous biopsy of the liver. To determine the validity of this assumption, we performed percutaneous biopsies of the liver under CT or sonographic guidance in 28 patients who had ascites and in 28 patients who did not have ascites and compared the complication rates in the two groups. Twenty-two patients (79%) in the group with ascites and 19 patients (68%) in the group without ascites had biopsies to determine the cause or extent of chronic liver disease. The remainder were oncologic patients who had biopsies to determine the cause of a focal hepatic mass. The complication rate in the patients who had ascites (32%) was less than that in the patients who did not have ascites (43%) (the difference did not reach statistical significance, p less than .30). In the ascites group, complications included transient hypotension (five patients), a mild-to-moderate fall in hematocrit (three patients), and a small leak of ascites from the biopsy site (one patient). In the control group, minor complications included transient hypotension (three patients), a mild-to-moderate fall in hematocrit (seven patients), and a small subcapsular hematoma (one patient). One major complication occurred in the control group: a patient required a blood transfusion because of the fall in his hematocrit. We conclude that the complication rate in liver biopsies guided by CT or sonography in the presence of ascites is not higher than similar biopsies done in the absence of ascites. Ascites should not be considered a contraindication for performing such biopsies.     

Disposition of [3H]flobufen and its active metabolite in rats

The present authors investigated the excretion, distribution and pharmacokinetics of the novel potential antirheumatic agent flobufen and its active metabolite after p.o. and i.v. doses of 2, 10 and 50 mg/kg administered to rats. The drug is resorbed well from the digestive tract and mostly it is metabolized to the principal metabolite M, which is only slowly excreted from the organism mainly by renal clearance. Within the whole dose range the kinetics of the drug is linear. Binding of flobufen and M to proteins is high (95-99%). The highest concentrations of radioactive metabolites (mostly M) were found in the plasma, liver, lungs, kidneys, connective tissue and inflammatory foci. The penetration of metabolites through the placenta and excretion in human milk are relatively important.     

The experimental pharmacotherapy of the liver lesion induced by indomethacin

In experiments on albino rats it was established that three administrations of indomethacin in a dose of 0.01 g/kg body weight induced a severe damage of the liver characterized by disturbances of hepatocytic membranes, bile-producing and protein-producing functions of the liver, an enhancement of lipid peroxidation, a decrease of reduced glutathione pool. Antioxidants (tocopherol acetate, essentiale, legalon, flacumin) limit manifestations of indomethacin, hepatotoxicity, as a result of which tha functional-biochemical disorders in the liver show up to a lesser degree. During the combined use of antioxidants in indomethacin-induced lesions of the liver their hepatoprotective activity increases.