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Biomedical subjects

S Jacob

Publications and source records attributed to S Jacob.

At least 19 recordsLinked to original sources
PubMed1999

Association of diabetes mellitus and chronic hepatitis C virus infection.

While patients with liver disease are known to have a higher prevalence of glucose intolerance, preliminary studies suggest that hepatitis C virus (HCV) infection may be an additional risk factor for the development of diabetes mellitus. To further study the correlation of HCV infection and diabetes, we performed a retrospective analysis of 1,117 patients with chronic viral hepatitis and analyzed whether age, sex, race, hepatitis B virus (HBV) infection, HCV infection, and cirrhosis were independently associated with diabetes. In addition, a case-control study was conducted to determine the seroprevalence of HCV infection in a cohort of 594 diabetics and 377 clinic patients assessed for thyroid disease. In the former study after the exclusion of patients with conditions predisposing to hyperglycemia, diabetes was observed in 21% of HCV-infected patients compared with 12% of HBV-infected subjects (P =.0004). Multivariate analysis revealed that HCV infection (P =.02) and age (P =.01) were independent predictors of diabetes. In the diabetes cohort, 4.2% of patients were found to be infected with HCV compared with 1.6% of control patients (P =.02). HCV genotype 2a was observed in 29% of HCV-RNA-positive diabetic patients versus 3% of local HCV-infected controls (P <.005). In conclusion, the data suggest a relatively strong association between HCV infection and diabetes, because diabetics have an increased frequency of HCV infection, particularly with genotype 2a. Furthermore, it is possible that HCV infection may serve as an additional risk factor for the development of diabetes, beyond that attributable to chronic liver disease alone.

Adult↗
PubMed1999

A dietary survey in Indian hemodialysis patients.

Malnutrition is a common problem in maintenance hemodialysis (MHD) patients, and compromised intake is an important cause. There is no information available about the nutrient intakes of MHD patients in India. The nutrient intakes of 106 MHD patients were studied cross-sectionally and on follow-up. A 24-hour recall was used on 4 consecutive days. After 2 months on dialysis, the mean energy intake was 29 +/- 6.6 kcal/kg ideal body weight (IBW) and the mean protein intake was.93 +/-.39 g/kg IBW (high biological value [HBV] protein 49% +/- 8.5%). Dietary deficiency of both protein and calories was present in 64.9%. Intake was better on nondialysis days compared with dialysis days, and in women and older patients. On follow-up there was no significant increase in food intake up to 6 months. After that, the total calorie intake increased significantly with a disproportionate drop in high biological value protein consumed and appeared to be derived predominantly from carbohydrate food (mean kcal/kg, 37 +/- 6.9; mean protein g/kg, 0.96 +/- 0.19; ratio of HBV protein to total protein consumed,.42 +/-.09). In summary this study showed suboptimal energy and protein intake in an MHD population. Intakes were further compromised on dialysis days, and with increasing time spent on dialysis, the quality of nutrient intake became poorer.

Adult↗
PubMed1998

The mammalian numb phosphotyrosine-binding domain. Characterization of binding specificity and identification of a novel PDZ domain-containing numb binding protein, LNX.

Numb is a phosphotyrosine-binding (PTB) domain-containing protein implicated in the control of cell fate decisions during development. A modified two-hybrid screen in yeast was used to identify Numb PTB domain-interacting proteins important for Numb function. Here we report the identification of a novel protein, LNX, which interacts specifically with the Numb PTB domain. Two differentially expressed LNX messages encode overlapping proteins with predicted molecular masses of 80 kDa (LNX) and 70 kDa (LNX-b). LNX and LNX-b contain unique amino-terminal sequences and share four PDZ domains. The unique amino-terminal region of LNX includes a RING finger domain. The Numb PTB domain binding region of LNX was mapped to the sequence motif LDNPAY, found in both protein isoforms. Mutational analysis of LNX and peptide competition experiments showed that phosphorylation of the tyrosine residue within this motif was not required for binding to the Numb PTB domain. Finally, we also provide evidence that tyrosine phosphorylation of the LDNPAY sequence motif in LNX could generate a binding site for the phosphorylation-dependent binding of other PTB domain-containing proteins such as SHC. We speculate that LNX may be important for clustering PTB-containing proteins with functionally related transmembrane proteins in specific membrane compartments.

Amino Acid Sequence↗
PubMed1998

Interactions of captopril and verapamil on glucose tolerance and insulin action in an animal model of insulin resistance.

We have shown previously that the combination of a long-acting, non-sulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor (trandolapril) and the Ca2+ channel blocker verapamil improve insulin-stimulated glucose transport in skeletal muscle of the obese Zucker rat, a model of insulin resistance, hyperinsulinemia, and dyslipidemia. In the present study, we investigated the interactions of chronic treatment (28 days) with verapamil (20 mg/kg) and a short-acting, sulfhydryl-containing ACE inhibitor (captopril, 50 mg/kg) in combination on insulinemia, lipidemia, glucose tolerance, and insulin action on skeletal muscle glucose transport (2-deoxyglucose uptake in epitrochlearis) in lean and obese Zucker rats. In lean animals, verapamil alone and in combination with captopril actually increased (P < .05) plasma insulin, whereas in obese animals, verapamil alone worsened the hyperinsulinemia already present, and this effect was abolished by cotreatment with captopril. Captopril alone or in combination with verapamil reduced plasma free fatty acid (FFA) levels in obese rats, but not in lean rats. Captopril alone reduced the glucose-insulin index in obese animals given an oral glucose load, and this was associated with a significant increase in insulin-mediated muscle glucose transport. The greatest improvement in these responses was elicited in obese animals receiving combined captopril and verapamil treatment, and was associated with increases in muscle GLUT-4 glucose transporter protein and hexokinase and citrate synthase activities. In conclusion, these findings indicate that the short-acting, sulfhydryl-containing ACE inhibitor captopril can elicit beneficial metabolic effects on the hyperinsulinemia, dyslipidemia, glucose intolerance, and insulin resistance of muscle glucose transport of the obese Zucker rat. Moreover, there is a positive interactive effect on these pathophysiological parameters between captopril and verapamil in this animal model of insulin resistance.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Maternal mortality in Utah.

OBJECTIVE: To determine trends in maternal deaths in Utah, identify opportunities for preventive intervention, and analyze the mechanism of reporting maternal deaths. METHODS: A retrospective review was performed of maternal death certificates and medical records in Utah from January 1, 1982, through December 31, 1994. RESULTS: Sixty-two maternal deaths were identified. The risk of maternal death increased with maternal age and parity. The classic triad of hemorrhage (n = 8), infection (n = 5), and preeclampsia-eclampsia (n = 3) remains an important contributor (16 of 62 or 25.8%). However, trauma (n = 10), pulmonary embolism (n = 10), and maternal cardiac disease (n = 9) now account for 46.8% (29 of 62) of maternal deaths. A greater number of direct obstetric causes of maternal death (n = 20) were deemed preventable than indirect obstetric causes (n = 1) or nonobstetric causes (n = 4). CONCLUSION: Trauma, pulmonary embolism, and maternal cardiac disease have emerged as the most common identifiable causes of maternal death. Improvements in prevention, earlier diagnosis, and aggressive treatment of these conditions are necessary to achieve the Public Health Service year 2000 objective of a 50% reduction in maternal mortality ratios (using the 1987 ratio as a baseline).

Adolescent↗
PubMed1998

Antihypertensive therapy and insulin sensitivity: do we have to redefine the role of beta-blocking agents?

Essential hypertension is, at least in many subjects, associated with a decrease in insulin sensitivity, whereas glycemic control is (still) normal. Metaanalyses of hypertension intervention studies revealed different efficacy of treatment on cerebral (cerebrovascular accidents [CVA]) and cardiac (coronary heart disease [CHD]) morbidity and mortality. Although CVA were reduced to an extent similar to that anticipated, the decrease in CHD was less than expected. These differences are likely to be caused by the different impact of concomitant cardiovascular risk factors, such as dyslipidemia, impaired glucose tolerance, and non-insulin-dependent diabetes mellitus on CHD and CVA. Frequently these cardiovascular risk factors are ineffectively controlled in hypertensive patients, and moreover, some of the widely used antihypertensive agents have unfavorable side effects and further deteriorate these particular metabolic risk factors. Therefore, the metabolic side effects of antihypertensive treatment have received more attention. During the past few years, studies demonstrated that most antihypertensive agents modify insulin sensitivity in parallel with alterations in the atherogenic lipid profile. Alpha1-blockers and angiotensin converting enzyme inhibitors were shown to either have no impact on or even improve insulin resistance and the profile of atherogenic lipids, whereas most of the calcium channel blockers were found to be metabolically inert. The diuretics and beta-adrenoreceptor antagonists further decrease insulin sensitivity and worsen dyslipidemia. The mechanisms by which beta-adrenoreceptor antagonist treatment exert its disadvantageous effects are not fully understood, but several possibilities exist: significant body weight gain, reduction in enzyme activities (muscle lipoprotein lipase and lecithin cholesterol acyltransferase), alterations in insulin clearance and insulin secretion, and, probably most important, reduced peripheral blood flow due to increase in total peripheral vascular resistance. Recent metabolic studies found beneficial effects of the newer vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. In many hypertensive patients, elevated sympathetic nerve activity and insulin resistance are a deleterious combination. Although conventional beta-blocker treatment was able to take care of the former, the latter got worse; the newer vasodilating beta-blocker generation seems to be capable of successfully treating both of them.

Adrenergic beta-Antagonists↗
PubMed1998

Validation of 24-hour dietary recall: a study in hemodialysis patients.

The 24-hour dietary recall method is frequently used for dietary assessment. However, it is subject to errors by both respondent and observer bias and is largely influenced by the motivation and recall ability of the respondent. The weighment method is regarded as the gold standard for estimating nutrient intake. This study was undertaken to assess the validity of dietary recall in a group of seven maintenance hemodialysis patients, who also had corresponding weighed food records. Actual food consumed and residue were weighed separately. A dietary recall was taken on the next day. Subjects were not allowed to take any food or beverage other than that served during the study period. A good agreement was obtained between dietary recall and the weighed food record (the difference was within 10% of the results of weighment), although there was a consistent underestimate by dietary recall. The results also suggested a training effect since improved recall was noted during the later weeks of the study, although this difference was not statistically significant. Therefore, dietary recall as a method of dietary assessment may be of special value in chronic hemodialysis patients in India, who are usually a motivated and informed group.

Adult↗
PubMed1998

Outcome from consecutive in-vitro fertilization/intracytoplasmic sperm injection attempts in the final group treated with urinary gonadotrophins and the first group treated with recombinant follicle stimulating hormone.

In the absence of specific dose equivalency data, the aim of this study was to compare the clinical results during the cross-over from menopausal urinary products (human menopausal gonadotrophin; HMG) to recombinant follicle stimulating hormone (FSH) follitrophin beta (FSHr) in order to determine whether the manufacturer's recommendation for equivalence of ampoule to ampoule (50 IU FSHr:75 IU HMG) would prove clinically correct. A total of 353 consecutive in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment cycles was studied between 1st September 1996 and mid-February 1997. This included cycles in the last 191 women receiving HMG and the first 162 taking FSHr. All were down-regulated using a gonadotrophin releasing hormone (GnRH) agonist long protocol method from day 1 of the cycle. Greater efficacy was seen in the HMG group in terms of days of stimulation required, need to increase dosage, cycle discontinuation, number of follicles punctured, the numbers of oocytes retrieved and their quality. The hormonal response to stimulation assessed by oestradiol concentrations on days 5, 8 and day of human chorionic gonadotrophin (HCG) was significantly lower in the FSHr group. The ratio of oestradiol per follicle and per oocyte was significantly lower in the FSHr group. There was a highly significant increase in cost with FSHr therapy. Clinical pregnancy rates were 14% per cycle with FSHr and 20% per cycle with HMG.

Drug Costs↗
PubMed1998

Effect of chronic bradykinin administration on insulin action in an animal model of insulin resistance.

The nonapeptide bradykinin (BK) has been implicated as the mediator of the beneficial effect of angiotensin-converting enzyme inhibitors on insulin-stimulated glucose transport in insulin-resistant skeletal muscle. In the present study, the effects of chronic in vivo BK treatment of obese Zucker (fa/fa) rats, a model of glucose intolerance and severe insulin resistance, on whole body glucose tolerance and skeletal muscle glucose transport activity stimulated by insulin or contractions were investigated. BK was administered subcutaneously (twice daily at 40 microg/kg body wt) for 14 consecutive days. Compared with a saline-treated obese group, the BK-treated obese animals had significantly (P < 0.05) lower fasting plasma levels of insulin (20%) and free fatty acids (26%), whereas plasma glucose was not different. During a 1 g/kg body wt oral glucose tolerance test, the glucose and insulin responses [incremental areas under the curve (AUC)] were 21 and 29% lower, respectively, in the BK-treated obese group. The glucose-insulin index, the product of the glucose and insulin AUCs and an indirect index of in vivo insulin action, was 52% lower in the BK-treated obese group compared with the obese control group. Moreover, 2-deoxyglucose uptake in the isolated epitrochlearis muscle stimulated by a maximally effective dose of insulin (2 mU/ml) was 52% greater in the BK-treated obese group. Contraction-stimulated (10 tetani) 2-deoxyglucose uptake was also enhanced by 35% as a result of the BK treatment. In conclusion, these findings indicate that in the severely insulin-resistant obese Zucker rat, chronic in vivo treatment with BK can significantly improve whole body glucose tolerance, possibly as a result of the enhanced insulin-stimulated skeletal muscle glucose transport activity observed in these animals.

Animals↗
PubMed1998

Ratio of male and female characters in a dream series.

The present study investigated the change in gender ratio of dream characters in relation to the dreamer's environment in waking-life and found a preponderance of male characters in the subject's dream while living in a 'male' environment which was not present while living in a 'female' environment. The results support the continuity hypothesis of dreaming and stress the importance of situational factors rather than personality factors in the explanation of the gender ratio of dream characters.

Dreams↗
PubMed1997

Comparative disposition of the antineoplastic agent 9-nitrocampotothecin and the inactive isomer 12-nitro camptothecin in CASE-bearing nude mice: effect of route of administration on tissue distribution.

PURPOSE: 9-Nitrocamptothecin (9-NC) and 12-nitrocamptothecin (12-NC) are synthetic structural analogues of camptothecin (CPT) which have been prepared to explore the structure/activity relationship of this group of compounds against a wide variety of experimental tumors. As part of our investigation of the pharmacology and the mechanism of tumor inhibition of these compounds, we examined the effect of route of administration on the distribution of tritium-labeled 9-NC and 12-NC, an active and a poor chemotherapeutic agent, respectively. METHODS: Quantitative whole-body autoradiography was used and our results were compared with previous results obtained with the parent compound CPT. RESULTS: These studies revealed that, independent of the route of administration, both CPT derivatives were rapidly distributed to gall bladder, gastrointestinal tract and kidney. The excretion from these organs was indicated by the high levels of radioactivity in urine (urinary bladder) and feces (large intestines). The studies also indicated that the distributions of 9-NC and 12-NC were qualitatively similar, but quantitatively higher uptake of radioactivity was observed in animals treated with 12-NC than in those treated with 9-NC at 30 min following treatment. With the exception of the late sampling time (12 h after administration), the accumulation of radioactivity in the lungs (bronchioles) of animals that received an intravenous (i.v.) dose of 9-NC or 12-NC was higher than those treated with an intramuscular (i.m.) dose. However, the retention of drug-derived radioactivity in the tumors of mice treated with an i.m. dose of 9-NC was higher than that in the tumors of i.v.-treated animals and was also higher than that in tumors of animals treated with 12-NC. CONCLUSIONS: These results suggest that higher accumulation of 9-NC in tumor tissues than of 12-NC may contribute to the more potent chemotherapeutic activity of the former agent. Our results also suggest that i.m. injection is a more effective route of administration than i.v. administration.

Animals↗
PubMed1997

Stimulation by alpha-lipoic acid of glucose transport activity in skeletal muscle of lean and obese Zucker rats.

Alpha-lipoic acid (ALA), a potent biological antioxidant, improves insulin action of skeletal muscle glucose transport and metabolism in both human and animal models of insulin resistance. In order to obtain further insight into the potential intracellular mechanisms for the action of ALA on insulin-stimulated glucose transport in skeletal muscle, we investigated the effects of direct incubation with ALA (2 mM) on 2-deoxyglucose (2-DG) uptake by epitrochlearis muscle from either insulin-sensitive lean (Fa/-) or insulin-resistant obese (fa/fa) Zucker rats. ALA stimulated 2-DG uptake in muscle of lean animals by 76%, whereas ALA stimulated 2-DG uptake by only 48% in muscle from obese animals. The stimulation of 2-DG uptake due to ALA was enhanced 30-55% in the presence of insulin. In contrast, ALA action on 2-DG uptake was not additive with the effects of electrically-stimulated muscle contractions in either insulin-sensitive or insulin-resistant muscle. Wortmannin (1 microM), an inhibitor of phosphotidylinositol-3-kinase, completely inhibited insulin action on 2-DG uptake, but inhibited ALA action by only 25%. Collectively, these results indicate that although a portion of ALA action on glucose transport in mammalian skeletal muscle is mediated via the insulin signal transduction pathway, the majority of the direct effect of ALA on skeletal muscle glucose transport is insulin-independent.

Animals↗
PubMed1997

Comparison of quantitative HCV RNA assays in chronic hepatitis C.

We compared the relative sensitivities of first-and-second generation branched nucleotide assays (Quantiplex HCV RNA 1.0 and 2.0, respectively, Chiron, Emeryville, Calif) for the detection of hepatitis C virus (HCV) RNA to that of a commercially available quantitative reverse transcriptase polymerase chain reaction (RT-PCR) method (Monitor, Roche Molecular Systems, Nutley, NJ) in 53 patients with chronic hepatitis C. The sensitivities of the second-generation branched DNA (bDNA) and RT-PCR assays were similar (91% and 92%, respectively), and both were significantly more sensitive (P < .001) than the first-generation method. Moreover, both assays detected HCV RNA in all 11 patients with type 2a, 2b, or 3a genotypes vs 45% with the HCV RNA 1.0 bDNA assay. We examined 174 serum samples by the bDNA 2.0 and RT-PCR assays. Major quantification differences were noted on a given specimen with the RT-PCR method reporting values an average 41-fold lower (range, 0-703-fold) than those obtained with the bDNA assay. We conclude that both methods can be used to detect HCV RNA in patients who are infected with the genotypes that are most commonly encountered in the United States. The HCV RNA 2.0 bDNA assay may offer advantages when attempting to quantify high-level viremia.

Chronic Disease↗
PubMed1997

Mechanism of femoral nerve palsy complicating percutaneous ilioinguinal field block.

Femoral nerve palsy has been reported after percutaneous ilioinguinal field infiltration with general anaesthesia for inguinal herniorrhaphy. The mechanism whereby this could occur was studied in cadaver dissections. It was found that the plane between the transversus abdominis muscle and the transversalis fascia was continuous laterally with the tissue plane deep to the iliacus fascia, which is the plane containing the femoral nerve. Injection of methylene blue 1 ml into this plane resulted in pooling of dye around the femoral nerve. Femoral nerve palsy may result from infiltration of a sufficient volume of local anaesthetic into the plane between the transversus abdominis muscle and the transversalis fascia with tracking of the injectate deep to the iliacus fascia to affect the femoral nerve. This finding has important implications for the performance of a percutaneous ilioinguinal field block particularly in day surgery provision.

Anesthetics, Local↗
PubMed1997

A dual technique for identification of the epidural space.

A method of identifying the epidural space is described in which the traditional loss of resistance to air technique is combined with amplification of the sound made by the epidural needle as it traverses the interspinous ligament and the ligamentum flavum and then enters the epidural space. The method retains all the advantages of the loss of resistance to air technique whilst, in addition, the auditory amplification gives a slightly earlier warning of entry into the epidural space. The apparatus necessary is readily available and the technique is easy to use. In addition to being useful in difficult epidurals, the technique would also be an excellent teaching aid.

Air↗
PubMed1997

Studies on gastric mucosal microcirculation. 1. The nature of regional variations induced by ethanol injury.

BACKGROUND/AIMS: The focal nature of gastric ulcers raises the possibility of underlying regional disturbances in gastric mucosal microcirculation. This study employed fluorescent in vivo microscopy with the aim of directly investigating the response of several areas of the gastric mucosa to 60% ethanol. METHODS: Changes in macromolecular leakage of fluorescein labelled albumin, vessel diameter, and acridine red labelled leucocyte adhesion and rolling were assessed over a period of two hours. A total of 0.5 ml 60% ethanol was topically applied for five minutes to the exteriorised gastric mucosa of anaesthetised rats. RATS: Three distinct patterns of response were found. Areas of lesion formation were small and occurred within five minutes. These areas showed persistent blood flow stasis throughout the course of the experiment, increased leakage (p < 0.02), and no leucocyte adhesion. Peripheral to the lesion, sustained leakage (p < 0.02) was found with adherence of leucocytes (p < 0.01) after lesion formation. Sites more remote to any lesion showed transient leakage and significant numbers of 'rolling' leucocytes (p < 0.01) were observed again after the lesion had formed. CONCLUSIONS: Despite widespread exposure of the entire gastric mucosa to 60% ethanol the resultant mucosal injury was limited. Widespread vascular damage was found reflected by macromolecular leakage, the pattern of which showed regional variation.

Administration, Topical↗
PubMed1997

Studies on the gastric mucosal microcirculation. 2. Helicobacter pylori water soluble extracts induce platelet aggregation in the gastric mucosal microcirculation in vivo.

BACKGROUND: The exact mechanisms by which Helicobacter pylori infection results in gastric mucosal injury are unclear. AIMS: To assess in vivo whether H pylori extracts could initiate an inflammatory response in the rat gastric mucosal microcirculation. METHODS: Extracts of H pylori, Escherichia coli, or distilled water were administered topically to the gastric mucosa of anaesthetised animals. Fluorescence in vivo microscopy assessed macromolecular leakage of labelled albumin from mucosal vessels, leucocyte adherence/rolling, and platelet activity for 90 minutes. RESULTS: H pylori induced increases (p < 0.001) in adherent platelet thrombi and circulating platelet emboli after five and 15 minutes respectively. Adherent platelet thrombi (mean of four per field of view) remained significantly increased throughout the experiment, but circulating emboli (maximum of five at 30 minutes) decreased with time. Leucocyte adherence did not occur although early transient rolling was observed. An 11% increase (p < 0.02) in albumin leakage occurred after five minutes only. The induction of platelet aggregation was only observed following H pylori administration. CONCLUSION: This in vivo study demonstrated the ability of H pylori extracts to promote platelet aggregation within gastric mucosal microvessels. Recruitment of leucocytes was not observed. The results suggest that the early events associated with H pylori infection are platelet aggregation with perhaps subsequent leucocyte recruitment by activated platelets.

Animals↗