Effect of low dietary calcium on bone metabolism in the SENCAR mouse

The SENCAR (sensitive to carcinogenesis) mouse is a unique tool for investigating the interaction between a specific defect in intracellular signaling, dietary calcium, and metabolic bone disease. The SENCAR mouse was developed by selective breeding for enhanced sensitivity to two-stage carcinogenesis. Its major genetic defect, which renders it exquisitely sensitive to stimulation with diacylglycerol or phorbol esters, is in the regulatory domain of protein kinase C, one of the primary intracellular mediators of hormonal effects. At sexual maturity, SENCAR mice are large and have big bones, but our previous pharmacokinetic studies showed that they accumulate lesscalcium under normal conditions and lose more calcium under adverse conditions than do other, standard strains of mice. To histologically define the effect of low dietary calcium on bone metabolism, we performed histomorphometric analysis of tetracycline-labeled sections of femoral bone from male SENCAR mice maintained on calcium-sufficient and calcium-deficient diets during the critical period from 10 to 14 weeks of age. The bone volume, absolute osteoid volume, and mineral apposition rate were lower at 14 than at 10 weeks of age in SENCAR mice fed 0.02 or 0.6% calcium diets. Calcium deficiency increased the architectural disarray and the probability of observing focal discontinuities in the growth plate. Thus, characteristic features of impaired bone metabolism (low bone volume and apposition rate) develop early in SENCAR mice and are exacerbated by low dietary calcium. Detailed examinations of the histology and biochemistry of SENCAR mouse bone will provide insights into the mechanisms by which specific defects in the signal transduction of protein kinase C contribute to impaired bone metabolism.     

Evidence for a direct stimulatory effect of cibenzoline on insulin secretion in rats.

The effect of cibenzoline succinate, a new antiarrhythmic agent, was studied on insulin secretion in rats. Experiments were performed both in vivo and in vitro using two preparations: the isolated perfused pancreas and isolated islets. In anaesthetized rats, cibenzoline was able to increase plasma insulin levels and to reduce glycaemia. These effects were observed at 1 mg/kg i.v. in fed rats and at 3 mg/kg i.v. in fasted rats. In the isolated pancreas perfused in the presence of a slightly stimulating glucose concentration (8.3 mM), cibenzoline (2 and 6 microM) elicited a progressive and sustained insulin response in a concentration-dependent manner. In the presence of a non-stimulating glucose concentration (4.2 mM), cibenzoline was ineffective at 2 microM and slightly increased basal insulin release at 6 microM. In isolated islets incubated with 8.3 mM glucose, cibenzoline (6 and 20 microM) caused a concentration-dependent stimulation of insulin release. It is concluded that cibenzoline stimulates insulin secretion by a direct action on pancreatic B cells in rats.     

Preliminary results of intermittent retrograde cerebral perfusion during proximal aortic arch surgery.

OBJECTIVE: Continuous retrograde cerebral perfusion during aortic arch surgery is associated with cerebral edema. In this report, we describe the clinical use of a new type of intermittent retrograde cerebral perfusion. SUBJECTS AND METHODS: Fourteen patients with a Stanford type A dissection were included in this study. With the usual method of retrograde cerebral perfusion, about 2,500 mL venous blood is drained from bicaval cannulae into a hard-shell reservoir, and oxygenated blood is perfused through the superior vena caval cannula. The flow rate is 300 mL/min. After about 15 min, retrograde perfusion is discontinued, and drainage from the bicaval cannulae is restarted. When a bloodless field is necessary, perfusion also is discontinued. RESULTS: Two to seven cycles of intermittent retrograde cerebral perfusion were administered (average, 3.1+/-0.4, mean+/-SD). The total retrograde perfusion time was 36.0+/-1.9 min which was equivalent to 74.8% of the circulatory arrest time. No patient developed edema of the upper body. The time to wake-up was 3 to 14 h (average, 6.5+/-1.0 h). No patient suffered any neurologic complications even though the time of circulatory arrest was greater than 60 min in four cases. Head magnetic resonance imaging or computed tomography was performed in 12 cases, and no evidence of hypoxic brain injury was detected. CONCLUSIONS: Our clinical experience using a moderate amount of intermittent retrograde cerebral perfusion is superior to continuous retrograde cerebral perfusion for protecting the brain during aortic arch surgery.     

Incidence of spontaneous hearing threshold shifts during modern concert performances.

OBJECTIVES: Concerts have long periods of intense sound with short break intervals. Hearing concerns are well known to performers; concertgoers largely ignore them. Preperformance and postperformance audiograms were compared to assess hearing threshold shifts with and without earplugs. METHODS: A prospective, randomized study in which 29 volunteers attended 3 concerts, encompassing 3 music genres. Audiograms, seating location, sound intensity, and earplug-use data were collected. Data were analyzed to determine frequency test-retest variability. RESULTS: Sound levels averaged 99.8 dBA, and the maximum was 125.6 dBA. Sixty-four percent (9/14) of participants without earplugs showed significant threshold shifts compared with 27% (4/15) of those using earplugs. No significant differences existed between music genres or seating location. CONCLUSIONS: This study showed a high incidence of threshold shifts in unprotected concertgoers. Sound levels exceeded all Occupational Safety and Health Act rules despite standardized sound systems. A significant reduction in threshold shifts was seen with the use of earplugs. EBM rating: A-1b.     

HepG2 cell binding activities of different hepatitis b virus isolates: inhibitory effect of anti-HBs and anti-preS1(21–47)

The antigenic relationships among different hepatitis B virus (HBV) isolates were investigated by using monoclonal antibodies (MAbs) specific for HBs, preS2 (pHSA binding site), and preS1 (hepatocyte receptor-binding site) epitopes in a double immunoradiometric assay. In order to define possible functional differences resulting from structural and antigenic differences in the HBV env protein, the HBV isolates were compared in an in vitro cell-binding assay based on the attachment of 125I-labeled HBV to human hepatoma HepG2 cells. We provided evidence for a variability of the expression of preS1 and preS2 specificities in the peplomer (glyco)protein of HBV depending on d/ysubtype of HBsAg, which could affect the viral infectivity. We showed that the integrity of the HBV envelope structure associated with a large expression of preS1(21–47) epitopes is an essential factor for effective binding to HepG2 cells. Interestingly, the HBs-specific MAbs directed to disulfide-bond-dependent epitopes were found to be the best inhibitors of the preS1-HepG2 cell interaction (>50% at the final concentration of 0.5 μg/ml). The MAb F35.25 directed to the preS1(21–47) sequence corresponding to the hepatocyte receptor recognition site was, however, also found to inhibit binding. Thus, our results demonstrate the abilities of both anti-HBs and anti-preS(21–41) to block the attachment of complete HBV particles to HepG2 cells, suggesting that these antibodies should be virus neutralizing and would be expected to confer protection against reinfection.     

Laparoscopic Cholecystectomy for Acute Cholecystitis: Prospective Trial

p < 0.00001) and for hydrops (28.5%) and empyema of the gallbladder (28.5%) ( p = 0.004). The difference in conversion between the group with acute necrotizing (gangrenous) cholecystitis and the two groups with hydrops and empyema of the gallbladder was not statistically significant ( p = 0.07). The complication rates of acute cholecystitis, hydrops, empyema of the gallbladder, and gangrenous cholecystitis were 9.0%, 9.5%, 14.0%, and 20.0%, respectively ( p = NS). Patients with an operative delay of 96 hours or less from the onset of acute cholecystitis had a conversion rate of 23%, whereas a delay of more than 96 hours was associated with a conversion rate of 47% ( p = 0.022). The complication rate was 8.5% in the laparoscopic group and 27% in the converted group ( p = 0.013). Patients over 65 years of age, with a history of biliary disease, a nonpalpable gallbladder, WBC count over 13,000/cc, and acute gangrenous cholecystitis were independently associated with a high LC conversion rate; male patients, finding large bile stones, serum bilirubin over 0.8 mg/dl, and WBC count over 13,000/cc were independently associated with a high complication rate following laparoscopic surgery with or without conversion. Generally, LC can be performed safely for acute cholecystitis, with acceptably low conversion and complication rates. Different forms of cholecystitis carry various conversion and complication rates in selected cases. LC for acute cholecystitis should be performed within 96 hours of the onset of disease. Predictors of conversion and complications may be helpful when planning the laparoscopic approach to acute cholecystitis.