Search PubMed⌕ Search

Biomedical subjects

J C Russell

Publications and source records attributed to J C Russell.

At least 73 records · Page 4Linked to original sources
PubMed1996

Nuclear cholesterol content and nucleoside triphosphatase activity are altered in the JCR:LA-cp corpulent rat.

A nuclear pore complex-associated nucleoside triphosphatase (NTPase) activity is believed to provide energy for nuclear export of poly(A)+ mRNA. This study was initiated to determine if nuclear membrane lipid composition is altered during chronic hyperlipidemia, and what effect this has on NTPase activity. The JCR:LA-cp corpulent rat model is characterized by severe hypertriglyceridemia and moderate hypercholesterolemia, and thus represents an ideal animal model in which to study nuclear cholesterol and NTPase activity. NTPase activity was markedly increased in purified hepatic nuclei from corpulent female JCR:LA-cp rats in comparison to lean control rats as a function of assay time, [GTP], [ATP], and [Mg2+]. Nuclear membrane cholesterol and phospholipid content were significantly elevated in the corpulent animals. Nuclei of corpulent animals were less resistant to salt-induced lysis than nuclei of lean animals, suggesting a change in relative membrane integrity. Together, these results indicate that altered lipid metabolism in a genetic corpulent animal model can lead to changes in nuclear membrane lipid composition, which in turn may alter nuclear membrane NTPase activity and integrity.

Acid Anhydride Hydrolases↗
PubMed1996

Bile duct injuries, 1989-1993. A statewide experience. Connecticut Laparoscopic Cholecystectomy Registry.

OBJECTIVE: To review the incidence of major bile duct injuries (MBDI) during the shift from open (OC) to laparoscopic cholecystectomy (LC). DESIGN: Cohort analysis; minimum 15-month patient follow-up. SETTING: Acute care Connecticut hospitals. PATIENTS: Medical records of 30211 patients with cholecystectomy (OC or LC) reviewed; 47 cases of MBDI confirmed. MAIN OUTCOME MEASURE: Rate of MBDI. RESULTS: The incidence of MBDI in Connecticut hospitals rose from 0.04% in 1989 to 0.24% in 1991, then decreased to 0.11% in 1993. The increase was due to increased numbers of cholecystectomies and the initial increased risk of injury with LC. The 1990-through-1993 trend of decreasing incidence of LC MBDI was statistically significant (P=.02). By 1993, the difference between LC and OC was no longer significant (P=.81). Acute cholecystitis (odds ratio, 3.3) and gallstone pancreatitis (odds ratio, 3.6) increased the risk of MBDI during LC (P<.001). The LC MBDI more commonly were ductal excision or transections and often were not diagnosed intraoperatively. Intraoperative cholangiography facilitated intraoperative recognition and repair. Most patients (89%) underwent definitive management of the MBDI at the hospital of origin; of those, 5% required further interventions. CONCLUSIONS: Surgeries for acute cholecystitis and gallstone pancreatitis are associated with an increased risk for MBDI. Ductal anatomy, the timing of recognition of injury, and the method of repair dictate patient outcomes. Most patients are successfully managed at the hospital of origin, with good long-term results. Late bile duct strictures appear rare.

Acute Disease↗
PubMed1996

Managing gallbladder disease in a cost-effective manner.

The advent of laparoscopic cholecystectomy has resulted in an increase in total health care costs for gallstone disease despite a reduced unit cost for the procedure. The total number of cholecystectomies performed annually has increased, reflecting an alteration in referral patterns and threshold for surgery in these patients. Cost-effective management of gallstones is possible by adopting strategies to limit length of stay, with discharge possible on the day of surgery for many patients. Selective cholangiography, laparoscopic common bile duct exploration, and judicious postoperative use of ERCP also have a role in cost-effective gallstone treatment. Institutions must analyze all costs and patterns of use to make informed decisions about reusable and disposable instrumentation.

Ambulatory Surgical Procedures↗
PubMed1996

Effects of benfluorex on serum triacylglycerols and insulin sensitivity in the corpulent rat.

The JCR:LA-cp rat is obese, insulin resistant, and hyperlipidemic, and the males develop atherosclerosis and ischemic myocardial disease. Benfluorex at 35-40 mg.kg-1 body weight was administered in the food from 10 to 14 weeks of age and resulted in an initial 50% decrease in food consumption. Body weights of male and female rats initially decreased by about 7% and thereafter remained relatively constant, whereas control animals gained about 28% in weight over the treatment period. Pair-fed rats showed body weights virtually identical with those of benfluorex-treated animals. Benfluorex treatment and pair feeding decreased serum triacylglycerol concentrations by about 50%; there was a preferential loss of triacylglycerols containing longer chain fatty acids in the males, whereas this selectivity was not seen in the females. Hyperinsulinemic euglycemic insulin clamp studies were performed using [1-3H]glucose, a tracer that allows for the measurement of total glucose turnover, including hepatic uptake and release. In male cp/cp rats, hyperinsulinemia does not stimulate total glucose turnover, reflecting the very severe insulin resistance, and neither benfluorex treatment nor pair feeding increased total glucose turnover. Hyperinsulinemia in male cp/cp rats decreases hepatic glucose output, and benfluorex treatment or pair feeding reduced this insulin-mediated diversion of glucose to hepatic lipid synthesis. Hyperinsulinemia increases total glucose turnover in female cp/cp rats, and this was not increased further by benfluorex treatment or pair feeding. These effects emphasize the sex-specific differences in metabolic response of the rats to hyperinsulinemia and benfluorex treatment. Benfluorex ameliorates the obesity-insulin resistance-hyperlipidemia syndrome in this experimental model mainly by decreasing hyperphagia, with an accompanying improvement in hepatic glucose metabolism and a related reduction in hypertriglyceridemia.

Animals↗
PubMed1995

Overexpression of the obese gene in the genetically obese JCR:LA-corpulent rat.

Expression of the obese (ob) gene in JCR:LA-cp rats was examined. A 360 bp fragment of the conserved region of the gene was obtained by RT-PCR using total RNA isolated from adipose tissues of Sprague-Dawley (SD), JCR:LA-cp obese and lean rats. The three gene fragments were sequenced and shown to be identical. They were over 90% identical to the mouse ob gene sequence. The amplified fragments encode for 120 amino acids and have a glutamine residue at position +49. The gene was shown to be expressed only in adipose tissues, both white and brown. A ten-fold increase in ob mRNA was detected in white adipose tissues of obese animals compared to the lean ones of the JCR-LA:cp strain of rat. Ob gene was expressed in adipocytes and preadipocytes from the obese rat whereas in the lean and SD rats, ob gene expression was found in adipocytes only. No ob mRNA was detected in preadipocytes from the lean or SD rats, indicating a differentiation or maturation-dependent expression in normal rats.

Adipocytes↗
PubMed1995

Sexual dimorphism in the metabolic response to the calcium channel antagonists, diltiazem and clentiazem, by hyperlipidemic JCR:LA-cp rats.

The JCR:LA-cp rat is obese, insulin resistant, and hypertriglyceridemic. The obese male rats spontaneously develop atherosclerosis and ischemic myocardial lesions that are prevented by treatment with the calcium channel antagonist, nifedipine. Male and female JCR:LA-cp rats were treated with the calcium channel antagonist, diltiazem, and a closely related compound, clentiazem (at 30 mg/kg). Clentiazem, but not diltiazem, caused a significant increase in body weight of both sexes in the presence of decreased food consumption. Serum triacylglycerols were decreased by half by both drugs in male rats only, reflecting decreased very-low-density lipoprotein (VLDL) secretion. Females did not respond with lower concentrations of triacylglycerol (although VLDL secretion rate was decreased) and showed increased concentrations of cholesterol in the high-density lipoprotein (HDL) fraction. Diltiazem-treated male rats showed decreased VLDL particle size, together with a shift to shorter-chain fatty acids in the triacylglycerols. This effect was not seen with clentiazem treatment. There was no effect on insulin and glucose metabolism in these insulin-resistant animals. Calcium channel antagonists have complex metabolic effects in the hypertriglyceridemic rats, with highly beneficial hypolipidemic effects in the males that are not seen in the females. The sexual dimorphism of these responses is sex linked, but appears not to be due to the steroid sex hormones. These results suggest caution in the chronic treatment of human females with these agents and the importance of detailed human studies in females and individuals with the insulin-resistant/hypertriglyceridemic/obese syndrome.

Animals↗
PubMed1995

Metabolic abnormalities linked to obesity: effects of dexfenfluramine in the corpulent rat.

The JCR:LA-corpulent rat is a useful experimental model for the obese-diabetic-dyslipidemic syndrome that mimics the human condition and exhibits spontaneous development of atherosclerosis and myocardial lesions. A 30-day treatment of 6-month-old rats with dexfenfluramine 1, 2.5, and 5 mg per kilogram decreased body weight through loss of adipose tissue mass. The effect is caused primarily by the ability of dexfenfluramine to reduce food intake. The maximum depression of food intake and greatest weight loss is seen during the first 10 days of treatment in this experimental model; thereafter, body weight stabilizes. However, during this period, there is a marked decrease in serum concentrations of triglycerides, cholesterol, and insulin. Corpulent male rats were also treated from 6 to 37 weeks of age with dexfenfluramine 2.5 mg/kg. This also produces a sustained decrease in body weight and a decrease in circulating insulin concentrations. Preliminary evidence demonstrates a substantial decrease in the incidence of necrotic myocardial lesions produced by ischemic events. This study establishes that dexfenfluramine treatment can decrease the severity of associated risk factors for cardiovascular disease, namely obesity, diabetes, and dyslipidemias. Furthermore, we report the first evidence that long-term treatment with dexfenfluramine can largely prevent the occurrence of myocardial lesions and end-stage cardiovascular disease in this animal model prone to atherosclerosis.

Animals↗
PubMed1995

Increased glucose phosphorylating activity correlates with insulin secretory capacity of male JCR:LA-corpulent rat islets.

In this study the glucose responsiveness of isolated, overnight-cultured islets of obese LA/N-corpulent (cp/cp) rats was compared with glucose phosphorylating activity to determine whether changes in the function of glucokinase could be identified. Islets from both male and female cp/cp rats showed a left-shifted concentration response to glucose, with EC50 values of 1.5 and 4.6 mM, respectively, compared with 9.2 mM for lean control islets. Islets from cp/cp rats were partially resistant to inhibition by mannoheptulose, a glucokinase inhibitor. Minimum inhibitory concentrations were 10 mM in cp/cp vs. 3 mM in lean rat islets. Glucose phosphorylating potential was markedly increased in islets of male cp/cp, but not female cp/cp, compared with lean rats. The maximal velocity (Vmax) of hexokinase was increased 5-fold, while the Km of glucokinase was significantly decreased, in male cp/cp compared with the lean control islets(3.6 vs. 35.2 mM). The Km for glucokinase was also decreased in female cp/cp rat islets (17.2 mM). The data from male cp/cp rat islets are consistent with the idea that increased glucose phosphorylation capacity can contribute to insulin hypersecretion and an extreme leftward shift in the concentration-response curve. However, other factors must also be considered because female cp/cp rats have moderately increased insulin secretory capacity without marked changes in total glucose phosphorylating capacity.

Animals↗
PubMed1995

Diurnal variation of intensive running in food-deprived rats.

Manipulation of the food supply can induce either intense hyperactive wheel running or a fatal activity anorexia in rats that is strongly analogous to that seen in humans. The abnormal behaviour is accompanied by alterations in the diurnal pattern of activity. As part of a detailed study of hyperactivity and anorexia, spontaneous wheel running by male rats was studied under three conditions: ad libitum feeding; restriction to 15 g of food per day; and restriction to a single 90-min meal per day. Ad libitum fed rats increased their running at the rate of 440 +/- 60 m/day per day, stabilizing after day 10 at 6045 +/- 3010 m/day. The running occurred in short bursts throughout the dark period and at the beginning of the light period. Rats restricted to 15 g/day increased their running at the significantly greater (p < 0.001) rate of 1230 +/- 120 m/day per day, reaching 12 200 +/- 4 090 m/day by day 10 and thereafter stabilizing at 13 600 +/- 4 160 m/day. The running was initially triphasic and confined to the dark period but eventually progressed to a biphasic pattern. The rats restricted to a single 90-min access period to food each day showed an even greater rate of increase in running, attaining 1930 +/- 288 m/day per day (p < 0.02 vs. 15 g/day group). These animals decreased eating and decompensated by day 4. The diurnal pattern of activity was disturbed from day 1 of the protocol, and by day 4 the rats ran essentially continuously throughout the daily cycle. The sensitivity to hyperactivity is a function of the severity of food restriction in this animal model of hyperactivity. It is paralleled by a marked disturbance of the diurnal pattern of activity, suggesting that the hyperactivity is related to a basic central nervous system dysfunction.

Animals↗
PubMed1995

Inhibition of atherosclerosis and myocardial lesions in the JCR:LA-cp rat by beta, beta'-tetramethylhexadecanedioic acid (MEDICA 16).

Atherosclerosis-prone, insulin-resistant JCR:LA-cp male rats were treated from 6 weeks to 39 weeks of age with beta,beta'-tetramethylhexadecanedioic acid (MEDICA 16). Body weights were reduced (13%, P < .001) at 36 weeks without any accompanying decrease in food consumption. The treatment did not cause any significant change in plasma glucose or fasting insulin concentrations. There was a significant decrease in the extreme hyperplasia of the islets of Langerhans (38%, P < .05). The marked VLDL hypertriglyceridemia was decreased by 70% (P < .001), with an accompanying significant reduction in cholesterol concentrations. The severity of raised atherosclerotic lesions on the aortic arch was very markedly reduced (P < .01) in treated rats. This was accompanied by a reduction (P < .01) in the incidence of ischemic myocardial lesions. We conclude that long-term (33 weeks) MEDICA 16 treatment of an animal model for the obesity/insulin-resistant/hyperlipidemic syndrome not only markedly improved lipid metabolism, but also inhibited the development of advanced cardiovascular disease.

Animals↗
PubMed1994

Effects of obesity on bile formation and biliary lipid secretion in the genetically obese JCR:LA-corpulent rat.

Obesity, a known risk factor in cholesterol gallstone disease, is a favorable factor in the formation of bile supersaturated with cholesterol. Previous studies have been indirect and limited to human beings. To better define the hepatic secretory defect, we directly measured bile secretion and bile salt kinetics in a genetically obese rat. Common bile duct cannulations and 24-hr bile collections were performed on 11 obese (homozygous for the cp gene) and 11 lean (heterozygous cp) female rats of the JCR:LA-cp strain. In absolute terms, obese rats had normal bile salt secretion rates, 28% larger bile salt pools and 45% greater bile salt synthesis than lean controls. Obese rats had twice the total liver DNA content of lean controls, indicating twice the liver cell number. In terms relative to liver cell number, bile salt synthesis per milligram DNA was no different in the obese rats and controls. Biliary secretion under basal conditions, when expressed per total DNA content, was significantly decreased in the obese rats. Bile salt and phospholipid secretion per milligram DNA were decreased 54% and 49%, respectively, whereas a lesser 31% reduction in cholesterol secretion resulted in an increased cholesterol saturation index. The bile salt secretion rate and bile flow per milligram DNA were both decreased by half in obese rats, a cholestatic state likely reflecting the accumulation of intracellular microvesicular fat and mitochondrial damage. The secretory defect in this model of obesity is therefore less bile salt and phospholipid in relation to the cholesterol secreted per liver cell.

Animals↗
PubMed1994

Abnormal insulin and glucose metabolism in the JCR:LA-corpulent rat.

The JCR:LA-corpulent rat, if homozygous for the cp gene, exhibits a syndrome characterized by obesity, hypertriglyceridemia, and hyperinsulinemia with impaired glucose tolerance. The insulin and glucose metabolism of lean and obese rats of this strain have been studied with the euglycemic insulin clamp technique in 3- and 9-month-old rats. Lean rats require a twofold greater glucose infusion rate than obese rats at high plasma insulin concentrations. Glucose turnover was measured using isotope dilution techniques and 1-3H-glucose. Glucose turnover in lean rats of both sexes increases by a factor of 2 to 3 at very high insulin levels. In contrast, obese male rats are unable to respond even to extreme insulin levels with an increase in basal glucose turnover, indicating a profound insulin resistance. The calculated hepatic glucose production is inhibited by high insulin levels in the obese male rats, while lean animals show no inhibition. Thus, the obese male rats have normal basal glucose turnover, but have a profound insulin insensitivity in peripheral tissues. These abnormalities are present at a much reduced level in the obese female rats. These results are consistent with the hypothesis that the hyperinsulinemia, which correlates strongly with cardiovascular disease in this strain of rat, is secondary to a marked peripheral insulin resistance.

Aging↗
PubMed1994

Comparison of mortality rates for open and closed cholecystectomy in the elderly: Connecticut statewide survey.

The objective was to determine the safety of laparoscopic cholecystectomy for patients 65 years of age and older with symptomatic uncomplicated chronic gallbladder disease by comparing the mortality rate with open cholecystectomy. Connecticut Hospital Information Management Exchange and the Connecticut Society of American Board of Surgeons established a Connecticut Laparoscopic Registry made up of 33 acute care hospitals. A cohort longitudinal retrospective statewide registry collected data mortality rates on all 2865 elderly patients undergoing open (OC) or closed (LC) cholecystectomy for uncomplicated chronic cholecystitis. A database was established and continuously monitored from October 1, 1988, to December 31, 1992. Seven hundred sixty-one patients over 65 years of age underwent open cholecystectomy for uncomplicated chronic cholecystectomy during fiscal year 1989, with a mortality rate of 1.4%. The mortality rate of a similar cohort of patients who underwent laparoscopic cholecystectomy during fiscal years 1991 and 1992 was 0.3% and 0.6%, respectively. The mortality rate was further broken down into age subsets 65-69, 70-79, and 80+. The prelaparoscopic era (FY 1989) age subsets were compared with those of the laparoscopic era (FY 1991 and 1992). A statistically significant reduction (p = 0.01) in mortality rate was noted in the 70-79 age group following laparoscopic surgery. Laparoscopic cholecystectomy in the elderly for the treatment of symptomatic, uncomplicated chronic cholecystitis is as safe if not safer than open cholecystectomy as measured by mortality rate.

Aged↗
PubMed1994

Defective endothelium-dependent relaxation in the JCR:LA-corpulent rat.

Endothelium-dependent relaxation of the aorta was assessed in JCR:LA-corpulent rats, which are hyperphagous, hyperlipidemic, hyperinsulinemic, and obese and spontaneously develop atherosclerotic disease and myocardial lesions. The findings in corpulent rats (6 months of age) were compared with those in age-and sex-matched lean rats. Aortic rings were prepared and mounted in Krebs-Henseleit buffer in a conventional organ bath. The tissue was contracted with norepinephrine (10(-6) mol/L), and relaxation was induced using acetylcholine, the calcium ionophore A23187, or bradykinin. The maximum relaxation to acetylcholine was impaired in corpulent male rats compared with lean rats, whereas relaxation in response to the calcium ionophore was similar in the corpulent and lean animals. Aortic rings from corpulent and lean female rats showed no differences in response to acetylcholine or to the calcium ionophore. Removal of endothelium resulted in the loss of relaxant response to acetylcholine and the calcium ionophore. The relaxant responses to sodium nitrite were not significantly different in the corpulent and lean male rats when deendothelialized tissues were examined, but the sensitivity to sodium nitrite was significantly lower in rings from corpulent male rats with intact endothelium. There were no differences in the response to bradykinin between corpulent and lean rats. These findings suggest that there is a specific impairment of endothelium-dependent relaxation in the corpulent male rat that is limited to that mediated by muscarinic receptors. The possibility that endothelium-derived contractile agents are secreted in the vessels of corpulent male rats cannot be excluded.

Animals↗
PubMed1993

Laparoscopic cholecystectomy. A statewide experience. The Connecticut Laparoscopic Cholecystectomy Registry.

The explosion in laparoscopic cholecystectomy has posed many questions about its safety compared with the "gold standard" of open cholecystectomy. A statewide database was established in Connecticut to study these issues. Thirty-three (97%) of 34 hospitals in Connecticut participated in the study, which began at the inception of the laparoscopic procedure. Four thousand six hundred forty laparoscopic cholecystectomies were performed between May 1, 1990, and September 30, 1991. The overall conversion rate to open cholecystectomy was 6.9%. Conversions were more frequent with acute cholecystitis, in the elderly, and early in a surgeon's experience. The overall technical complication rate was 4.7%; common bile duct injuries occurred in 15 patients (0.3%). Complications decreased with increasing experience, to 0.98% after a surgeon's 75th procedure. Six patients (0.13%) died following laparoscopic cholecystectomy. The overall mortality rate associated with cholecystectomy fell during the study period. The frequency of cholecystectomy in Connecticut increased 29% with the advent of the laparoscopic procedure. The introduction of laparoscopic cholecystectomy has resulted in an increased frequency of surgery without an increase in surgical mortality. The incidence of common bile duct injuries was low. The decreasing incidence of technical complications demonstrates the learning curve for the procedure.

Adult↗
PubMed1993

Effect of castration on hyperlipidemic, insulin resistant JCR:LA-corpulent rats.

The JCR:LA-cp rat exhibits an obese, insulin resistant, hyperlipidemic syndrome. Obese male rats, only, develop atherosclerosis and ischemic myocardial lesions. The obese males have a greater hyperinsulinemia, but the obese females have a much greater hypertriglyceridemia due to hypersecretion of very low density lipoprotein (VLDL). Obese rats of both sexes were surgically castrated at 6 weeks of age to study the influence of testosterone and estrogen secretion on the sexual dimorphism of metabolism and disease in this strain. Castration had no effect on body weight or food consumption up to 16 weeks of age. Castrated male rats had significantly improved glucose tolerance, but a doubled serum triglyceride concentration. Castrated female rats showed approximately halved triglyceride levels. The distribution of the triglyceride molecular species was altered in the castrated male rats to resemble that of the females in which there was no change with castration. The effects suggest that testosterone may inhibit hepatic triglyceride secretion and promotes insulin insensitivity. Estrogen appears to exacerbate hepatic hypersecretion of VLDL. Castration had no effect on myocardial lesion frequency in 9-month-old rats of either sex. This implies that estrogen does not exert a direct protective effect against cardiovascular disease in this animal model.

Animals↗
PubMed1993

Maxillofacial prosthetics: vital signs.

A maxillofacial prosthetics survey was designed to record the response rate of prosthodontists regarding the frequency of maxillofacial procedures and insurance coverage in 1991. The survey explored variability with respect to membership in professional organizations, region, education, primary activity, and age of the prosthodontist. A total of 342 survey instruments were received from a total of 690 mailed. A total of 18,410 maxillofacial procedures were performed by the survey population. Members of the American Academy of Maxillofacial Prosthetics performed procedures at a significantly higher rate than did the members of the American College of Prosthodontists. A greater procedure rate was observed for prosthodontists in the South Midwest and Southwestern regions; the hospital setting; with 2 plus 1 year additional postgraduate maxillofacial training; and the 45- to 54-year age group. Insurance covered most maxillofacial procedures, but was not uniformly distributed within predictor variables nor between procedures.

Adult↗