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.     

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.     

Surgical management of 100 consecutive esophageal strictures

We report our experience with 100 consecutive patients with reflux-induced esophageal structure managed surgically. Preoperative dilatation, total fundoplication gastroplasty, and postoperative dilatation were used in 98 patients. Only two required resection of the esophageal structure. We have identified preoperative factors that adversely affect the results. These include scleroderma; previous operation, either esophageal or gastric, and the severity of the esophageal stricture. Results of nonresectional operations are excellent in uncomplicated cases or with the addition of only one complicating factor. The more complicating factors, the worse the results. Those patients with three preoperative complicating factors do poorly and may benefit from esophageal resection. We conclude that results obtained from this conservative nonresectional management program justify continuance of the use of total fundoplication gastroplasty with preoperative and postoperative dilatation in the management of such patients.     

Comparative toxicity of ethylene dichloride in F344/N, Sprague-Dawley and Osborne-Mendel rats

Studies were conducted to compare the toxicity of ethylene dichloride (EDC) in F344/N rats, Sprague-Dawley rats, and Osborne-Mendel rats. Ten rats/sex/group were exposed to EDC in drinking-water at 0, 500, 1000, 2000, 4000 and 8000 ppm for 13 wk. The highest concentration was limited by the maximum solubility of EDC in water (about 9000 ppm). In addition, F344/N rats (10/sex/group) were administered EDC in corn oil by gavage to compare toxicity resulting from bolus administration with that of continuous exposure in drinking-water. Gavage doses of EDC were within the range of total daily doses (in mg/kg body weight/day) resulting from exposure in drinking-water. EDC administered by gavage resulted in greater toxicity to F344/N rats than did administration of similar doses in drinking-water. All males receiving 240 and 480 mg/kg body weight and 9/10 females receiving 300 mg/kg body weight by gavage died before the end of the study. Necrosis of the cerebellum was observed in the brains of 3 males receiving 240 mg/kg body weight and 3 females receiving 300 mg/kg body weight. Hyperplasia and inflammation of the forestomach mucosa were observed in 8 male and 3 female rats that died or were killed in moribund condition. EDC caused minimal toxicity to F344/N, Sprague-Dawley and Osborne-Mendel rats at the drinking-water concentrations used in these studies; only female F344/N rats had EDC-related renal lesions. Based on mortality and EDC-related lesions, the no-effect levels for EDC administered by gavage to F344/N rats were 120 mg/kg body weight for males and 150 mg/kg body weight for females.     

Cytochrome P450 3A4 Activity in Premenopausal and Postmenopausal Women,Based on 6-β-Hydroxycortisol:Cortisol Ratios

Study Objective . To characterize cytochrome P450 (CYP) 3A4 activity in premenopausal and postmenopausal women by evaluating the urinary 6-β-hydroxycortisokcortisol ratio. Design . Prospective study. Subjects . Thirteen premenopausal and 13 postmenopausal women who were healthy and not receiving drugs known to affect CYP3A4 activity. Interventions . Beginning on day 2 of menses, premenopausal women collected first morning urine samples every other day for a complete menstrual cycle. Postmenopausal women collected first morning urine every other day for 28 days. Measurements and Main Results . Mean weekly 6-β-hydroxycortisol:cortisol ratios did not differ during the phase (week) of the menstrual cycle. Daily ratios did not differ in postmenopausal women. No difference between premenopausal and postmenopausal women was found on comparing overall median ratios. Conclusion . Cytochrome P450 3A4 activity as measured by 6-β-hydroxy cortisol:cortisol ratio did not differ by week of menstrual cycle, suggesting no menstrual cycle-related changes. Menopause does not appear to be associated with differences in CYP3A4 activity, compared with premenopause.     

Diagnosis of ligament rupture of the ankle joint: Physical examination, arthrography, stress radiography and sonography compared in 160 patients after inversion trauma

We prospectively enrolled 160 consecutive patients with inversion trauma of the ankle in a diagnostic protocol that included physical examination within 2 days and at 5 days after trauma, arthrography, stress radiography, and ultrasonography. 135 patients had pathological lateral ligament laxity on the later physical examination or lateral ligament rupture diagnosed on arthrography and they were operated on. 122 of these patients had ligament ruptures.

At clinical follow-up after a minimum of half a year, all of the patients who were not operated on had stable joints without signs of previous ligament ruptures.

Delayed physical examination at 5 days after the injury led to the highest overall sensitivity (96%) and specificity (84%) for the detection of a ligament rupture. Additional diagnostic procedures, at a considerable cost, yielded little additional information.     

A clinical trial on the prevention of catheter-related sepsis using a new hub model.

BACKGROUND: Catheter hub contamination is being increasingly recognized as a source of catheter-related sepsis. The authors have investigated the efficacy of a new hub design in preventing endoluminal catheter contamination and catheter-related sepsis arising at the hub. METHODS: Adult surgical and intensive care patients requiring a subclavian catheter for at least 1 week were randomly assigned to receive catheters with standard connectors (control group, n=73) or equipped with a new hub model (new hub group, n=78). Skin, catheter tip, and hub cultures were performed at the time the catheter was withdrawn because therapy was terminated or because of suspicion of sepsis, in which case peripheral blood cultures were taken. RESULTS: Of the 151 patients included, 15 (10%) developed catheter-related sepsis. Catheters were more often withdrawn because suspicion of infection in the control group (42 vs. 19%, p<0.005). Catheter sepsis rate was higher in the control group (16 vs. 4%, p<0.01) because of the low rate of catheter sepsis arising at the hub observed in the new hub group (1 vs. 11%, p<0.01). The prevalence of culture-positive catheter hubs without associated bacteremia (colonization) was higher in the control group (18 vs. 5%, P<0.03). CONCLUSIONS: A new catheter hub has proved to be useful in preventing endoluminal bacterial colonization and catheter-related sepsis in subclavian lines inserted for a mean of 2 weeks.