Reduction of embryonic intracellular pH: a potential mechanism of acetazolamide-induced limb malformations

The effects of acetazolamide on the developing rodent limb bud were postulated to result from a reduction of intracellular pH (pHi). Embryonic intracellular pH was calculated from transplacental distribution of the weak acid, 5,5'-dimethyloxazolidine-2,4-dione, in teratogenically sensitive (C57BL/6) and resistant (SWV) inbred mice. pHi was reduced by acetazolamide treatment in C57 embryos and limb buds but not in SWV samples. Acetazolamide teratogenesis can be exacerbated by coadministration of amiloride, presumably through inhibition of Na+/H+ exchange attributable to the latter agent. pHi reduction after such treatment was more profound than after acetazolamide alone, providing further support for the central hypothesis. pH was also reduced in other embryonic (embryo plasma) and extraembryonic compartments (exocoelomic fluid, amniotic fluid). pH changes in these compartments could also lead or contribute to abnormal development.     

Conjugation pathways in liver disease.

1. The activities of microsomal glucuronyltransferase and thiomethyltransferase, and those of cytosolic sulphotransferase, acetyltransferase, glutathione transferase and thiomethyltransferase were measured in abnormal (cirrhosis and chronic hepatitis) and normal livers. 2. Glucuronyltransferase and sulphotransferase were investigated with 2-naphthol and ethinyloestradiol as substrates. p-Aminobenzoic acid, benzo(a)pyrene-4,5-epoxide and 2-mercaptoethanol were the substrates of acetyltransferase, glutathione transferase and thiomethyltransferase, respectively. 3. Enzyme activities are expressed as nmol min-1 incubation mg-1 protein and the averages (+/- s.d.) are given. With 2-naphthol as substrate, the glucuronyltransferase activity was 6.55 +/- 4.10 (abnormal liver, n = 33) and 7.81 +/- 4.02 (normal liver, n = 26) (NS); whereas sulphotransferase activity was 0.28 +/- 0.18 (abnormal liver, n = 35) and 0.68 +/- 0.43 (normal liver, n = 26) (P less than 0.01). Glucuronyltransferase activity towards ethinyloestradiol was 102.5 +/- 56.9 (abnormal liver, n = 30) and 107 +/- 59.9 (normal liver, n = 26) (NS), whereas sulphotransferase activity was 57.2 +/- 36.0 (abnormal liver, n = 35) and 122 +/- 67.6 (normal liver, n = 28) (P less than 0.01). Acetyltransferase activity was 0.84 +/- 0.83 (abnormal liver, n = 35) and 3.84 +/- 1.65 (normal liver, n = 26) (P less than 0.01). Glutathione transferase activity was 0.83 +/- 0.68 (abnormal liver, n = 35) and 2.90 +/- 1.59 (normal liver, n = 25) (P less than 0.01) and thiomethyltransferase activity was 1.00 +/- 0.69 (abnormal liver, n = 34) and 3.99 +/- 1.49 (normal liver, n = 25) (P less than 0.01). 4. Liver disease lowers the activities towards the substrates studied of sulphotransferase, acetyltransferase, glutathionetransferase and thiomethyltransferase but not that of glucuronyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of rat liver preservation with Eurocollins and a modified University of Wisconsin solution: transplantation and isolation of hepatocytes for culture

The efficiency of Eurocollins or modified University of Wisconsin (UW) solution (MUW) in preserving rat livers was compared. After cold storage with one of the solutions, the livers were transplanted or perfused by collagenase for isolation of hepatocytes. Five of the 6 rats receiving a graft preserved with MUW versus none of the 6 rat receiving a graft preserved with Eurocollins solution survived 24 h or more. A significantly greater number of hepatocytes were isolated from livers preserved with MUW than from livers preserved with Eurocollins solution. This suggests a better reperfusion of MUW-preserved livers by collagenase resulting from less endothelial injury. LDH release by cultured hepatocytes, ketone body production and stimulation by glucagon were not significantly different between the two groups. These results confirm the superiority of MUW solution over Eurocollins in preserving liver grafts. They suggest that the advantage of MUW solution results from better protection of vascular endothelium rather than of hepatocytes.     

Uses and risks of drainage following elective colon resection. A prospective, randomized and controlled clinical study

The results of a controlled randomized and prospective clinical study including 113 patients from March 1987 until August 1988 showed that prophylactic drainage in elective resection for cancer of the colon was not necessary. 60 patients received a drain, 53 patients were not drained. The drain turned out to be ineffective even concerning its expected function of draining intraabdominal fluid: its diagnostic and therapeutic value failed in clinical practice. The rate of surgical complications--i.e. anastomotic leakage, impaired wound healing and relaparotomy--was significantly higher in the drained group. In elective colon resection the use of a drain as a routine procedure cannot be recommended.     

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.     

Bilateral congenital pseudarthrosis of the clavicle

Summary A case of bilateral congenital pseudarthrosis of the clavicle in a baby boy is described. The patient is fully asymptomatic, and no functional impairment is present. This is probably only the seventh case described of this rare congenital anomaly.     

Serum bone-gla protein after fracture

Serum bone Gamma-carboxyglutamic acid (bone-gla) protein (BGP), a marker of bone formation, was measured in serial blood samples drawn from 14 patients who had fractured at least one of their tibial or femoral diaphyses and from two other patients who had sustained major trauma without fracture but who had been immobilized. A total of 85 samples were taken and analyzed during the first three months after the fractures occurred. Serum BGP significantly increased and positively correlated with the time that had elapsed after the fracture, with an average twofold increase after two months. The fracture site and the duration of immobilization had no influence on the serum BGP levels. Serum BGP levels from the two non-fractured cases increased in the first two weeks with no subsequent consistent trend. These data suggest that serum BGP increases one to two months after a major fracture, possibly as a manifestation of bone repair. Further studies are required to determine the potential clinical value of serum BGP in the management of such patients.     

Hypertension in Jordanian children: a retrospective analysis of 70 cases

Seventy patients, aged 1–20 years, were seen at Jordan University Hospital with high blood pressure (BP) over a 3-year period. BP values ranged from 140 to 230 mmHg for systolic pressure and from 90 to 130 mmHg for diastolic pressure. Essential hypertension was seen in only 6 patients (8.6%); secondary hypertension (n=64 or 91.4%) was due to renal parenchymal diseases (RPD) in 46 patients (65.7%), reno-vascular lesions in 8 (11.4%), renal transplantation in 5 (7.2%), teenage pregnancy in 4 (5.7%), and phaeochromocytoma in 1 patient (1.4%). The aetiologies of RPD were as follows: end-stage renal disease requiring dialysis in 14 patients, acute glomerulonephritis in 14, idiopathic nephrotic syndrome in 10, chronic renal insufficiency in 5, and polycystic kidney in 3 patients. Surgical cure of hypertension was achieved in 5 of the children with reno-vascular lesions and in the patient with phaeochromocytoma.     

No excess of DR*3/4 in Ashkenazi Jewish or Hispanic IDDM patients

The gene frequencies, haplotype relative risks, and zygotic assortments of HLA-DR in three ethnically defined samples of insulin-dependent diabetes mellitus (IDDM) patients were determined in a prospective family study. Although DR3 and DR4 were positively associated with IDDM in the probands of 123 northern European, 94 Ashkenazi Jewish, and 49 New York Hispanic families, significant excess of DR*3/4 heterozygotes was observed only among the probands from families of northern European ancestry. There was also a significant decrease in the frequency of Bw62,DR4 haplotypes derived by northern European patients from their mothers compared with their fathers. This difference, together with data reported in the literature, suggests that the expressivity of the susceptible genotype(s) in IDDM patients may be modified by protective maternal effects associated with Bw62,DR4 and probably other DR4 haplotypes. Samples of IDDM patients from populations with high frequencies of these modifiers should have different DR-gene frequencies contributed by fathers and mothers, capable of accounting for the observed Hardy-Weinberg disequilibrium. We postulate that, because the mechanism of action of these modifiers is distinct from that of the susceptibility gene, the difference must be considered in devising strategies for elucidation of the mode of inheritance of the disease and for understanding the molecular nature of the susceptibility.