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Biomedical subjects

S Arora

Publications and source records attributed to S Arora.

At least 55 records · Page 3Linked to original sources

Alcohol levels are increased in social drinkers receiving ranitidine.

OBJECTIVE: Ranitidine increases blood alcohol concentrations by decreasing the first pass metabolism of ethanol. The effect of ranitidine on alcohol levels has been found to be variable when using large doses of alcohol or conditions in which its first pass metabolism is known to be minimal. Despite a consensus that the drug increases alcohol levels after small doses of ethanol, this effect has been considered inconsequential, because of the low alcohol levels. However, social drinking comprises repetitive consumption of small doses of alcohol and the ranitidine effect could thereby be potentiated. METHODS: To study this factor, alcohol levels were determined by breath analysis in nine men (social drinkers), after four drinks of 0.15 g/kg ethanol given postprandially every 45 min, before and after ranitidine (150 mg b.i.d. for 7 days). RESULTS: Their blood alcohol increased with repeated doses, reaching peak values of 24+/-3 mg/dl before ranitidine and 33+/-2 after ranitidine (p = 0.04). In seven of the nine subjects blood alcohol exceeded 25 mg/dl, a level at which impairment of judgment and of finely tuned skills occurs and which exceeds legal limits of driving in some European countries. Moreover, the high levels persisted for a longer time with than without the drug. These effects were associated with a 62% decrease in first pass metabolism. CONCLUSION: Under conditions mimicking social drinking, ranitidine increases blood alcohol to levels known to impair psychomotor skills needed for driving.

Adult↗

Major factors influencing breastfeeding rates: Mother's perception of father's attitude and milk supply.

OBJECTIVE: To determine factors influencing feeding decisions, breastfeeding and/or bottle initiation rates, as well as breastfeeding duration. SETTING: A family medicine practice of a 530-bed community-based hospital in northwestern Pennsylvania. PARTICIPANTS: All mothers whose infants received well-child care from birth to 1 year of age. OUTCOME MEASURE: A survey of 28 simple questions was developed and mailed to 245 mothers. The survey assessed: 1) demographics, 2) prenatal and postnatal care, 3) sources of breastfeeding information, 4) timing of decision, 5) preference, 6) type of feeding selected, 7) duration of breastfeeding, 8) factors influencing decisions to breastfeed and/or to bottle-feed, and 9) factors that would have encouraged bottle-feeding mothers to breastfeed. RESULTS: The breastfeeding initiation rate was 44.3%. By the time the infant was 6 months old, only 13% of these were still breastfeeding. The decision to breastfeed or to bottle-feed was most often made before pregnancy or during the first trimester. The most common reasons mothers chose breastfeeding included: 1) benefits the infant's health, 2) naturalness, and 3) emotional bonding with the infant. The most common reasons bottle-feeding was chosen included: 1) mother's perception of father's attitude, 2) uncertainty regarding the quantity of breast milk, and 3) return to work. By self-report, factors that would have encouraged bottle-feeding mothers to breastfeed included: 1) more information in prenatal class; 2) more information from TV, magazines, and books; and 3) family support. CONCLUSIONS: To overcome obstacles, issues surrounding perceived barriers, such as father's attitude, quantity of milk, and time constraints, need to be discussed with each parent. To achieve the goal of 75% of breastfeeding mothers, extensive education regarding the benefits must be provided for both parents and optimally the grandmother by physicians, nurses, and the media before pregnancy or within the first trimester.

Adult↗

A strategy for vascular services--testing the 600,000 population model.

BACKGROUND: Vascular services' delivery has been criticised, and re-organisation based on a 600,000 population model suggested. We assessed the feasibility of this model in three geographically disparate English regions. METHODS: Surgical arterial activity by Trust was analyzed using 1994/95 data from Hospital Episode Statistics. A postal survey of acute Trusts was used to assess vascular facilities and personnel. Distances between hospitals and enumeration districts were mapped using a Geographical Information System. MAIN OUTCOME MEASURES: Number (proportion) of Trusts performing over 100 arterial procedures a year. Number (proportion) of Trusts with a vascular on-call rota. Proportion of population likely to live more than 40 km away (equivalent to 1 h blue-light ambulance travel time) from a vascular unit under the proposed model. RESULTS: Twelve of the 32 Trusts (38%) performed over 100 arterial procedures annually; 23 Trusts completed the survey. Of these, five (22%) had a vascular on-call rota. Under the 600,000 model, in East Anglia a further 16.5% of the population would live > 40 km from a vascular unit. In Wessex, a further 0.4% of the population would live > 40 km from a vascular unit. Impact on access in North West Thames was negligible. CONCLUSIONS: A 600,000 population model could be feasible in urbanized regions, but not in geographically remote ones.

Delivery of Health Care↗

Clinical features of hepatitis C-infected patients with persistently normal alanine transaminase levels in the Southwestern United States.

Approximately one third of patients with chronic hepatitis C virus (HCV) infection have normal alanine transaminase (ALT) levels. We studied the clinical, biochemical, virological, and histological features in patients with persistently normal ALT. A case-control study was conducted on 275 patients with chronic HCV infection, including 75 patients with persistently normal ALT and 200 patients with abnormal ALT. Persistently normal ALT was defined as 4 consecutive ALT values in each patient within a period of 12 months. The average age of the patients was 44 years (range 18 to 69 years). More non-Hispanic whites had persistently normal ALT. The mean serum ferritin level was significantly lower in patients with persistently normal ALT as compared with abnormal ALT (128 +/- 92 ng/mL and 224 +/- 128 ng/mL), respectively (P =.017). The mean HCV-RNA level was significantly lower in patients with persistently normal ALT as compared with abnormal ALT (12 x 10(5) +/- 2.8 x 10(6) copies/mL and 33 x 10(5) +/- 8.0 x 10(6)), respectively (P =.02). Histologically, patients with persistently normal ALT had less severe portal inflammation (P <.05), lobular inflammation (P =.003), piecemeal necrosis (P =.002), fibrosis (P <.05), lower prevalence of cirrhosis (P =.007), as well as a slower fibrosis progression rate (P <.001). Chronic hepatitis C patients with persistently normal ALT have low-activity grade and stage on liver biopsy. In these patients the hepatitis C RNA level was lower compared with abnormal ALT patients, which may explain the slower fibrosis progression rate.

Adult↗

Insulin-like growth factor-1 receptors mediate infragenicular vascular smooth muscle cell proliferation in response to glucose and insulin not by insulin receptors.

PURPOSE: Vascular smooth muscle cell (VSMC) proliferation is an early event in the pathogenesis of atherosclerosis. Insulin and glucose are known to stimulate the growth of VSMC. Cell membrane receptors play an important role in the proliferation of VSMC in response to growth factors. Insulin and insulin-like growth factor-1 (IGF-1) have demonstrated a cross reactivity for receptor binding and function. By using monoclonal antibodies directed against insulin (IRA) and IGF-1 (IGF-1RA) receptors, we attempt to further delineate the mechanism for the proliferation of VSMC in response to insulin and glucose. METHODS: Human infragenicular VSMC isolated from diabetic patients undergoing below-knee amputations were used. Cells from passages 3 to 6 were grown in serum-free media with a glucose concentrations of 0.1% or 0.2%, both with and without insulin (100 ng/mL). The baseline cell density was 4,635 +/- 329 cells/mL. IRA or IGF-1RA was added to the media, with the control group receiving neither antibody. Cells were grown in 5% CO2 at 37 degrees C for 6 days. Analysis of variance was used for statistical analysis, with P <0.05 considered significant. In addition, DNA synthesis was measured using thymidine incorporation assays in the same groups of cells receiving IRA, IGF-1RA, and no antibody. RESULTS: IGF-1RA prevented the proliferation of VSMC in response to insulin and glucose, while IRA had no effect on cell growth. There was no significant growth when IGF-1RA was added to the media, while the control group and the group receiving IRA demonstrated significant growth compared with the baseline concentration of 4,635 +/- 329 cells/mL at all concentrations of insulin and glucose. [3H]thymidine incorporation assays confirmed the cell count results. CONCLUSIONS: These results suggest that the mitogenic effects of insulin and glucose on infragenicular VSMC are due to stimulation of the IGF-1 receptor. VSMC antiproliferative strategies employing receptor blockade should be directed against the IGF-1 receptor, not the insulin receptor.

Analysis of Variance↗

Accelerated carotid artery disease after high-dose head and neck radiotherapy: is there a role for routine carotid duplex surveillance?

PURPOSE: High-dose external radiotherapy used in the treatment of head and neck carcinoma has been implicated as a risk factor for accelerated atherosclerotic disease of the carotid arteries. However, how radiotherapy affects atherosclerotic disease is controversial, and little data exist to demonstrate a strong relationship between radiotherapy and progressive carotid disease. METHODS: We performed a retrospective chart review of 69 patients (all men) who underwent duplex ultrasound scanning examinations for carotid disease between 1993 and 1998. Twenty-three patients had received high-dose radiotherapy for the treatment of head and neck carcinoma within the past 12 years (group 1; mean age, 67.8 years), and 46 patients were randomly selected as age-matched control subjects (group 2; mean age, 68.3 years). The mean radiation dose was 6060 +/- 182 rads, and the average interval between radiotherapy and ultrasound scanning was 6. 5 +/- 1.8 years. There was no significant difference between the two groups in the presence of these comorbidities: diabetes mellitus, coronary artery disease, hypertension, tobacco use, hypercholesterolemia, peripheral vascular disease, or stroke. Similarly, there was no difference in the indications for the duplex scanning studies. RESULTS: Five of the 23 patients in group 1 (21. 7%) were found to have advanced carotid disease (70% to 99% stenosis); four patients were symptomatic, three patients went on to endarterectomy, and one patient was awaiting surgery. Two of the 46 patients in the control group (4%) had advanced carotid disease. One patient was symptomatic, and both patients underwent endarterectomy. A significant difference in the prevalence of advanced disease between the two groups was noted (P =.037). Sixteen patients who survived irradiation underwent a second duplex scanning study and had evidence of progressive disease with significant increases in peak systolic velocities. CONCLUSION: High-dose radiotherapy to the head and neck region may be a significant risk factor for accelerated carotid atherosclerotic disease. Routine carotid duplex surveillance may be warranted in this high-risk patient population.

Aged↗

Folic acid inhibits homocysteine-induced proliferation of human arterial smooth muscle cells.

PURPOSE: An elevated plasma homocysteine level has been identified as an independent risk factor for atherosclerosis. Whether this represents a marker for vascular disease or a direct effect on the vasculature remains unclear. Because vascular smooth muscle cells (VSMCs) play an integral role in the atherosclerotic process, we studied the effect of homocysteine on human infragenicular VSMC proliferation and the role of folic acid in reversing the homocysteine effect. METHODS: Human infragenicular VSMCs harvested from amputation specimens were studied. Various cell groups were exposed to physiologic (6.25 micromol/L and 12.5 micromol/L) and pathologic (25 micromol/L to 500 micromol/L) concentrations of homocysteine. Similar groups were simultaneously exposed to 20 nmol/L of folic acid. Cell counts and DNA synthesis, as reflected by [methyl-(3)H]-thymidine incorporation, were performed at 6 days and 24 hours, respectively. Additional groups were exposed to various combinations of folic acid (20 nmol/L), vitamin B(6) (145 nmol/L), and vitamin B(12) (0.45 nmol/L) in the presence of homocysteine (25, 50, and 250 micromol/L). RESULTS: Homocysteine resulted in a dose-dependent increase in DNA synthesis and cell proliferation. Cell counts increased significantly at homocysteine concentrations ranging from 25 micromol/L to 500 micromol/L (P <.05), with a maximal increase of 98% at 500 micromol/L of homocysteine. The addition of 20 nmol/L folic acid resulted in significant inhibition of cell proliferation at all homocysteine concentrations studied (P <.001). Maximal inhibition of 70% occurred in the cells exposed to 50 micromol/L of homocysteine. The increases in [methyl-(3)H]-thymidine incorporation ranged from 36% at 6 micromol/L homocysteine to a maximum of 247% at 500 micromol/L homocysteine. All increases were statistically significant (P <.05). The addition of 20 nmol/L folic acid resulted in significant inhibition of DNA synthesis (P <.002). Vitamins B(6) and B(12) did not demonstrate significant antiproliferative properties. CONCLUSION: A possible role of homocysteine in the formation of atherosclerotic lesions is through a direct proliferative effect on VSMCs in a dose-dependent fashion. Folic acid intake at levels available in dietary supplements may prove protective in hyperhomocysteinemia-induced atherosclerosis. Vitamins B(6) and B(12) alone do not appear to exhibit a substantial inhibitory effect in the setting of elevated homocysteine levels.

Cell Division↗

A case-control study of the factors associated with spontaneous resolution of hepatitis C viremia.

OBJECTIVE: Infection with the hepatitis C virus (HCV) becomes chronic in 85% of the infected individuals. We studied risk factors that may predict clearance of HCV. METHODS: A case-control study compared the association between risk factors and viral clearance. Viral clearance was defined as presence of a positive HCV antibody test plus negative HCV test by polymerase chain reaction (PCR). Forty-four cases and 214 controls with persistent viremia were identified in a database of patients evaluated at the Gastroenterology Clinic of the University of New Mexico. RESULTS: Of all 258 HCV-antibody-positive patients, 17% had a negative test by PCR. The multivariate logistic regression revealed that a history of parenteral exposure and a long time interval since the most recent exposure were both associated with an increased likelihood of persistent viremia, whereas subjects who had been monogamous for longer time periods were more likely to have cleared HCV from their serum. A low serum level of ferritin also conferred protection against persistent viremia. Case and control subjects did not differ with respect to their demographic characteristics, occurrence of comorbid disease, previous medical history, occurrence of sexually transmitted diseases, blood group, and risky health or sexual practices. CONCLUSIONS: These data suggest that route of exposure and time when exposure occurred are important in the development of persistent HCV infection.

Adult↗

A case-control study of risk factors for sporadic hepatitis C virus infection in the southwestern United States.

OBJECTIVE: We performed a case-control study to evaluate risk factors and possible modes of transmission for hepatitis C virus (HCV) infection in patients with no history of blood transfusion or injection drug use. METHODS: Study subjects were selected from among patients seen in gastroenterology outpatient clinics at a university medical center in the southwestern United States. The study group consisted of 58 patients (12%) with chronic HCV infection who reported no history of transfusion or injection drug use, among a total of 477 patients evaluated for a positive HCV antibody test. These 58 patients were matched by age, ethnicity, and gender with 58 control patients diagnosed with gastroesophageal reflux attending the same clinics. Patients and controls were subjected to structured interviews and review of medical records. RESULTS: A variety of variables were significantly associated with increased risk of sporadic HCV infection, including a history of tattoos, needlestick exposure, a history of sexually transmitted disease, intercourse with an injection drug user, five or more lifetime sexual partners, intercourse during menses (for women), lower income, and heavy alcohol intake (>60 g/day). Multivariate analysis identified a history of sexually transmitted disease, heavy alcohol intake, and the presence of a tattoo as independent risk factors for sporadic HCV. In addition, six cases and one control had a history of needlestick exposure. Of the cases, 88% had at least one of these four risk factors, as compared with 26% of controls (odds ratio = 16.5; 95% confidence interval = 4.0-68.8). CONCLUSIONS: A history of sexually transmitted disease, heavy alcohol intake, the presence of tattoos, and a history of needlestick exposure were identified as risk factors for sporadic hepatitis C in this case-control study. If we include all patients with a history of blood transfusion or injection drug use, only 2% of the total 477 HCV patients had no identified risk factors.

Acupuncture Therapy↗

Visceral leishmaniasis masquerading as tuberculosis in a patient with AIDS.

We report a case of visceral leishmaniasis presenting as significant lymphadenopathy in a patient with acquired immune deficiency syndrome. The lymphadenopathy was initially suspected to be tubercular in nature on pathological examination. This report highlights the increasing incidence of acquired immune deficiency syndrome and Leishmania co-infection in India, and the importance of demonstrating tubercle bacilli on culture before suggesting a diagnosis of tuberculosis.

AIDS-Related Opportunistic Infections↗

The effect of hormonal replacement therapy on the vascular reactivity and endothelial function of healthy individuals and individuals with type 2 diabetes.

Estrogens protect healthy women from cardiovascular disease. However, epidemiological data suggest that women with diabetes are denied the cardioprotection associated with estrogens. Whether or not hormonal replacement therapy (HRT) confers cardiovascular benefits in postmenopausal women with diabetes is not known. The aim of this study was to examine the effects of HRT on the microvascular reactivity and endothelial function of individuals with and without diabetes. We studied the following groups of individuals: premenopausal healthy women [n = 28, age 41 +/- 8 yr (mean +/- SD)], premenopausal women with type 2 diabetes (n = 16, age 43 +/- 6 yr); postmenopausal healthy women (n = 12, age 57 +/- 4 yr), postmenopausal women with diabetes (n = 17, age 62 +/- 5 yr); postmenopausal healthy women on HRT (n = 13, age 51 +/- 5 yr), postmenopausal women with diabetes on HRT (n = 11, age 57 +/- 7 yr). We used laser Doppler flowmetry to measure forearm cutaneous vasodilatation in response to iontophoresis of 1% acetylcholine (endothelium dependent) and 1% sodium nitroprusside (endothelium independent). The endothelium-dependent vasodilation was significantly higher in premenopausal healthy women (180 +/- 67%; increase over baseline) compared to premenopausal diabetic women (87 +/- 41%; P < 0.001). endothelium-dependent vasodilation was also higher in postmenopausal healthy women on HRT (143 +/- 52) compared with postmenopausal diabetic women on HRT (86 +/- 61), postmenopausal healthy women without HRT (104 +/- 43), and postmenopausal diabetic women without HRT (74 +/- 28; P < 0.001). A similar pattern of responses was observed in the endothelium-independent vasodilation (premenopausal healthy women, 126 +/- 56; premenopausal diabetic women, 88 +/- 26; postmenopausal healthy women on HRT, 121 +/- 37; postmenopausal diabetic women on HRT, 88 +/- 41; postmenopausal healthy women without HRT, 84 +/- 36; and postmenopausal diabetic women without HRT, 73 +/- 36; P < 0.001). Soluble intercellular adhesion molecule (sICAM) was also measured among all the women with diabetes. Premenopausal women with diabetes (248.9 +/- 56 ng/ml) and postmenopausal women with diabetes on HRT (257.7 +/- 49 ng/ml) had lower sICAM levels compared with the postmenopausal diabetic women without HRT (346.4 +/- 149 ng/ml; P < 0.05). We conclude that menopausal status and type 2 diabetes are associated with impaired microvascular reactivity. HRT substantially improves microvascular reactivity in postmenopausal healthy women. In contrast, the effect of HRT on the microvascular reactivity of postmenopausal diabetic women is less apparent. However, the use of HRT among women with diabetes is associated with lower sICAM levels, suggesting an attenuation in endothelial activation.

Acetylcholine↗

Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes.

Abnormalities in vascular reactivity in the micro- and macrocirculation are well established in type 2 diabetes. However, little is known about changes in vascular reactivity in those at risk for developing type 2 diabetes. To address this situation, the vascular reactivity in both the micro- and macrocirculation was studied in four age and sex comparable groups: 30 healthy normoglycemic subjects with no history of type 2 diabetes in a first-degree relative (controls), 39 healthy normoglycemic subjects with a history of type 2 diabetes in one or both parents (relatives), 32 subjects with impaired glucose tolerance (IGT), and 42 patients with type 2 diabetes without vascular complications (diabetes). Laser Doppler perfusion imaging was used to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent) and 1% sodium nitroprusside (SNP) (endothelium-independent), whereas high-resolution ultrasound images were used to measure brachial artery diameter changes during reactive hyperemia. Plasma concentrations of endothelin-1 (ET-1), von Willebrand factor (vWF), soluble intercellular adhesion molecule (sICAM), and soluble vascular cell adhesion molecule (sVCAM) were also measured as indicators of endothelial cell activation. The vasodilatory responses to Ach, expressed as percent increase of blood flow over baseline, were reduced in relatives (98 +/- 48, mean +/- SD), IGT (94 +/- 52), and diabetes (74 +/- 45) compared with controls (126 +/- 67) (P < 0.001 controls versus relatives, IGT, and diabetes). The responses to SNP were similarly reduced: controls (123 +/- 46), relatives (85 +/- 46), IGT (83 +/- 48), and diabetes (65 +/- 31) (P < 0.001 controls versus relatives, IGT, and diabetes) as were the responses in the brachial artery diameter during reactive hyperemia: controls (13.7 +/- 6.1), relatives (10.5 +/- 6.7), IGT (9.8 +/- 4.5), and diabetes (8.4 +/- 5.0) (P < 0.01 controls versus relatives, IGT, and diabetes). Women had greater responses than men in both the micro- and macrovascular circulatory tests, but a similar progressive reduction was observed in both sexes with increasing degrees of glucose intolerance. A significant inverse correlation was found between microvascular reactivity and systolic blood pressure, fasting plasma glucose, HDL cholesterol, fasting plasma insulin, and homeostasis model assessment (HOMA) values, an index of insulin resistance. BMI and diastolic blood pressure had a significant inverse correlation only with endothelium-dependent vasodilation. In the macrocirculation, systolic blood pressure, HbA1c, HDL cholesterol, and HOMA had significant correlation with brachial artery diameter changes. Compared with control subjects, ET-1 was significantly higher in all groups, vWF was higher only in the diabetic group, sICAM levels were higher in the IGT and diabetic groups, while sVCAM concentrations were higher in the relatives and those with diabetes (P < 0.05). On stepwise multivariate analysis, age, sex, fasting plasma glucose, and BMI were the most important contributing factors to the variation of vascular reactivity. Addition of all clinical and biochemical measures explained only 32-37% of the variation in vascular reactivity. These results suggest that abnormalities in vascular reactivity and biochemical markers of endothelial cell activation are present early in individuals at risk of developing type 2 diabetes, even at a stage when normal glucose tolerance exists, and that factors in addition to insulin resistance may be operative.

Acetylcholine↗

CYP2E1 expression in human lymphocytes from various ethnic populations.

BACKGROUND: Monitoring CYP2E1 levels in alcoholic individuals holds inherent appeal because such determinations might indicate individuals at increased risk for alcoholic liver disease. We previously demonstrated that lymphocyte CYP2E1 expression reflects in vivo activity of the hepatic enzyme. METHODS: To further validate this approach, the current investigation compared lymphocyte CYP2E1 content and chlorzoxazone pharmacokinetics in 51 alcoholic and nonalcoholic White, Navajo, and Mexican American subjects. After an oral dose of chlorzoxazone, blood samples were collected and lymphocytes isolated. RESULTS: Alcoholics exhibited a 2-fold elevation in lymphocyte CYP2E1 messenger ribonucleic acid (mRNA) and protein compared to nonalcoholics. Chlorzoxazone clearance rates were 1.9-fold higher and area under the concentration curve (AUC) values 1.8-fold lower in alcoholic individuals compared to nonalcoholics. Furthermore, chlorzoxazone clearance rates correlated (r = 0.55, p < 0.01, n = 38) with lymphocyte CYP2E1 mRNA content, and transcript levels further correlated (r = 0.52, p < 0.001, n = 38) with CYP2E1 protein content. To compare phenotype with genotype, restriction fragment length polymorphism analyses on deoxyribonucleic acid samples were performed to identify polymorphisms in the CYP2E1 gene. No subjects were homozygous for rare alleles c2 or C. Nonetheless, 27% of the Navajos and 15% of the Mexican Americans were heterozygous for the c2 allele. Two White subjects appeared heterozygous (c1/c2) when RsaI was used to characterize CYP2E1 genotype but homozygous (c1/c1) at the PstI locus. Fifteen percent of Mexican American subjects, 20% of Navajo subjects, and 6% of White subjects were heterozygous for the C allele. Neither CD nor cl/c2 genotypes were associated with alcoholism. CONCLUSIONS: Human lymphocyte CYP2E1 mRNA levels may be useful predictors of alcohol-mediated alterations in hepatic CYP2E1 activity. Moreover, ethnicity does not appear to play a major role in the levels of expression of lymphocyte CYP2E1.

Adult↗