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Biomedical subjects

S Arora

Publications and source records attributed to S Arora.

At least 73 records · Page 4Linked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

Central venous pressure from common iliac vein reflects right atrial pressure.

PURPOSE: To determine whether central venous pressure at the common iliac vein reflects right atrial pressure in adult patients. METHODS: In this prospective, non-blinded study 26 mechanically-ventilated adult patients were studied. Simultaneous pressure readings were obtained from the right atrium (TCVP) and the common iliac vein (ACVP). RESULTS: There was a correlation between TCVP and ACVP (r = 0.987; P < 0.0001). The mean difference between TCVP and ACVP was 0.93 mm Hg. And the limits of agreement were: -1.93 to 1.77 mm Hg. CONCLUSION: Venous pressure recorded from the common iliac vein reflects that in the right atrium. Adopting a femoral route for central venous pressure measurement may avoid some of the complications associated with the subclavian route.

Adolescent↗
PubMed1998

Estrogen improves endothelial function.

PURPOSE: To determine the effect of estrogen on endothelium-dependent relaxation in the cutaneous microcirculation of women. METHODS: Three groups of women participated in the study. Group 1 (n = 20) was premenopausal and had a mean age of 39 years (range 24-50 years). Group 2 (n = 9) was postmenopausal and had a mean age of 58 years (range 53-65 years). Group 3 (n = 11) was postmenopausal and taking estrogen replacement therapy; the mean age was 53 years (range 43-58 years). Eleven women in group 1 underwent testing twice, once during menstruation (mean serum estradiol level 73 +/- 30 pg/ml) and once during midcycle (mean serum estradiol level 268 +/- 193 pg/ml; p = 0.003). Single-point laser Doppler ultrasound and laser Doppler imaging with a scanner were used to measure vasodilatation in the forearm skin in response to iontophoresis of 1% acetylcholine (endothelium dependent) and 1% sodium nitroprusside (endothelium-independent smooth muscle relaxant). RESULTS: All three groups were matched for body mass index and fasting glucose, total, high-density lipoprotein, and low-density lipoprotein cholesterol and triglyceride levels. All women had normal blood pressure, and none smoked. Mean serum estradiol levels were 196 +/- 170 pg/ml (group 1), 35 +/- 12 pg/ml (group 2), and 107 +/- 78 pg/ml (group 3) (p = 0.004). Maximum microvascular vasodilatation (percentage increase over baseline) in response to acetylcholine was reduced in group 2 (93% +/- 43%) compared with group 1 (187% +/- 63%) and group 3 (142% +/- 56%) (p = 0.001). The response to sodium nitroprusside also was diminished in group 2 (73% +/- 27%) compared with group 1 (126% +/- 45%) and group 3 (100% +/- 32%) (p = 0.02). Within group 1 the acetylcholine response was higher during the midcycle phase (186% +/- 31%) compared with the menstrual phase (147% +/- 57%) (p < 0.05). The sodium nitroprusside response also was higher during the midcycle phase (144% +/- 31%) compared with the menstrual phase (94% +/- 41%) (p < 0.05) CONCLUSION: The results indicate that estrogens might enhance endothelium-dependent and endothelium-independent vasodilatation in the microcirculation of women.

Acetylcholine↗
PubMed1998

Lower extremity arterial reconstruction in the very elderly: successful outcome preserves not only the limb but also residential status and ambulatory function.

PURPOSE: The purpose of this study was to evaluate our results with lower extremity arterial reconstruction (LEAR) in patients 80 years of age or older and to assess its impact on ambulatory function and residential status. METHODS: We performed a retrospective review of all patients 80 years of age or older undergoing LEAR at a single institution from January 1990 through December 1995. Preoperative information regarding residential status and ambulatory function was obtained from the hospital record and vascular registry. Telephone interviews with patients or next of kin were undertaken to provide information regarding postoperative residential status and ambulatory function. Residential status and level of ambulatory function were graded by a simple scoring system in which 1 indicates living independently, walking without assistance; 2 indicate living at home with family, walking with an ambulatory assistance device; 3 indicates an extended stay in a rehabilitation facility, using a wheelchair; and 4 indicates permanent nursing home, bedridden. Preoperative and postoperative scores for both residential status and ambulatory function were compared. Kaplan-Meier survival curves were generated for graft patency, limb salvage, and patient survival. RESULTS: Two hundred ninety-nine lower extremity bypass operations were performed in 262 patients 80 years of age or older (45% men, mean age 83.6 years, range 80 to 96 years). Sixty-seven percent of the patients had diabetes mellitus. Limb salvage was the indication for operation in 96%. The preoperative mean residential status and ambulatory function scores were 1.79+/-0.65 and 1.55+/-0.66, respectively. The perioperative mortality rate at 30 days was 2.3%. The median length of hospital stay decreased from 16 days in 1990 to 8 days in 1995 (range 4 to 145 days). Eighty-seven percent of grafts were performed with the autologous vein. The 5-year primary, assisted primary, and secondary graft patency rates for all grafts were 72%, 80%, and 87%, respectively. The limb salvage rate at 5 years was 92%. The patient survival rate at 5 years was 44%. The postoperative residential status and ambulatory function scores were 1.95+/-0.80 and 1.70+/-0.66, respectively. Overall scores remained the same or improved in 88% and 78% of patients, respectively. CONCLUSION: LEAR in octogenarians is safe, with graft patency and limb salvage rates comparable to those reported for younger patients. LEAR preserves the ability to ambulate and reside at home for most patients.

Activities of Daily Living↗
PubMed1998

Reactive hyperemic response of the brachial artery: comparison of proximal and distal occlusion.

RATIONALE AND OBJECTIVES: The authors compared the postocclusion hyperemic responses of the brachial artery after occluding blood flow proximal to and distal to the studied area. MATERIALS AND METHODS: Response of the brachial artery to hypoxia was evaluated with duplex Doppler ultrasound in 13 healthy subjects. A pneumatic tourniquet was first positioned 2-5 cm superior to the left elbow, proximal to the area of artery studied. Two hours later the response was remeasured with the tourniquet positioned 2-5 cm inferior to the elbow, distal to the artery studied. Arterial diameter, mean and peak flow velocities, and heart rate were assessed. RESULTS: No significant differences were observed between measurements of baseline and postischemic arterial diameter, percentage diameter change, baseline mean arterial blood flow velocity, baseline peak arterial blood flow velocity, or postischemic heart rate obtained with proximal occlusion of the artery and those obtained with distal occlusion. In contrast, mean and peak postischemic arterial blood flow velocity and preocclusion heart rate were higher in measurements made during proximal artery occlusion. Significant correlation was found between measurements of percentage change in artery diameter obtained with proximal artery occlusion and those obtained with distal occlusion (r = 0.611, P < .05). CONCLUSION: There are no major differences in postischemic changes in brachial artery diameter related to reactive hyperemia between blood flow occlusion applied proximal and distal to the studied area. However, there are significant differences in the mean and peak systolic velocities. Either occlusion site can be used for clinical studies if arterial diameter change is monitored, but if velocity measurements are being compared, a single occlusion site should be chosen.

Adult↗
PubMed1998

Management of presumed intraocular tuberculosis: possible role of the polymerase chain reaction.

PURPOSE: A highly selective technique of polymerase chain reaction (PCR) was performed for detection of Mycobacterium tuberculosis from aqueous samples of 45 patients to evaluate its role in initiating antituberculosis treatment in patients with presumed intraocular tuberculosis. METHODS: Forty-five patients were divided into three groups. Group I included 17 patients of presumed intraocular tuberculosis, group II 13 disease controls and group III had 15 normal controls. Patients with positive PCR were offered antituberculosis chemotherapy and followed up for a minimum of 18 months. RESULTS: Ten patients in group I, 3 in group II and none in group III were positive for Mycobacterium tuberculosis by PCR. Ten patients with positive PCR for Mycobacterium tuberculosis (8 in group I and 2 in group II) were treated with antituberculosis chemotherapy and all showed resolution of inflammation without any recurrence over 18 months of follow-up. Two PCR positive patients treated with steroids alone, however, did not show complete resolution and had recurrent attacks. CONCLUSION: These results suggest that antituberculosis treatment in PCR positive patients leads to resolution of inflammation and elimination of recurrences, most likely by eliminating Mycobacterium tuberculosis from the intraocular tissues.

Adolescent↗
PubMed1998

A proteinase K inhibitor using alpha,beta-unsaturated (dehydro) residues: a presumptive model.

Enzymes of the subtilisin family, of which proteinase K is a member, have been studied extensively on account of their numerous biological applications. Specific inhibitors of the proteinases are of immense importance in regulating their activity so as to protect the cells against uncontrolled proteolysis. Using the specific design principles of peptides containing dehydro-Alanine (deltaAla), generated by our theoretical calculations, we present here the design of an inhibitor of proteinase K. Energy minimization and molecular modeling of the interaction of the designed tetrapeptide with the recognition site of proteinase K indicate that it is an effective inhibitor.

Binding Sites↗
PubMed1998

Colonic mucosal concentrations of folate correlate well with blood measurements of folate status in persons with colorectal polyps.

BACKGROUND: Estimates of habitual dietary folate intake are known to be imprecisely correlated with systemic measures of folate status. Furthermore, measurements of blood folate concentrations may not accurately reflect the concentration of folate in tissues of interest. This issue is important for assessing folate status in the colorectal mucosa because low dietary intake or blood concentrations of folate are associated with an increased risk of colorectal neoplasia. OBJECTIVE: We examined whether conventional measures of folate in blood and a more sensitive, inverse indicator of systemic folate status, serum homocysteine, accurately reflected folate concentrations in human colonic mucosa obtained by endoscopic biopsy. DESIGN: In 30 persons with colorectal polyps, blood samples were taken and biopsies of normal rectosigmoid mucosa performed at the time of colonoscopic polypectomy. Serum, red blood cell, and colonic mucosal folate and serum homocysteine concentrations were measured. RESULTS: Serum and red blood cell folate and serum homocysteine concentrations accurately reflected colonic mucosal folate concentrations; among these, serum homocysteine correlated best with mucosal concentrations. Folate concentrations in the normal rectosigmoid mucosa were significantly lower in persons with adenomatous polyps than in those with hyperplastic polyps (P=0.04). Conventional measures of systemic folate status were not significantly lower in those with adenomas, although serum homocysteine was mildly elevated (P=0.04). CONCLUSIONS: Our data underscore the ability of systemic measures of folate status, particularly serum homocysteine, to reflect folate concentrations in the colonic mucosa. Nevertheless, future studies that examine the ability of folate to modulate colorectal carcinogenesis may benefit from direct measurement of folate in the colon.

Adenoma↗
PubMed1998

Differences in foot and forearm skin microcirculation in diabetic patients with and without neuropathy.

OBJECTIVE: We have compared the hyperemic response to heat and the endothelium-dependent and endothelium-independent vasodilatation between the dorsum of the foot and the forearm in diabetic neuropathic and non-neuropathic patients and healthy control subjects. RESEARCH DESIGN AND METHODS: We studied the cutaneous microcirculation in the forearm and foot in 15 diabetic patients with neuropathy, in 14 diabetic patients without neuropathy, and in 15 control subjects matched for age, sex, BMI, and in the case of diabetic patients, for the duration of diabetes. Patients with peripheral vascular disease and/or renal impairment were excluded. The cutaneous microcirculation of the dorsum of the foot and the flexor aspect of the forearm was tested in all subjects. Single-point laser Doppler was employed to measure the maximal hyperemic response to heating of the skin to 44 degrees C and laser Doppler imaging scanner was used to evaluate the response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent response) and 1% sodium nitroprusside (NaNP) (endothelium-independent response). RESULTS: The transcutaneous oxygen tension was lower in the neuropathic group at both foot and forearm level, while the maximal hyperemic response to heat was similar at the foot and forearm level in all three groups. The endothelium-dependent vasodilation (percent increase over baseline) was lower in the foot compared to the forearm in the neuropathic group (23 +/- 4 vs. 55 +/- 10 [mean +/- SEM]; P < 0.01)], the non-neuropathic group (33 +/- 6 vs. 88 +/- 14; P < 0.01), and the control subjects (43 +/- 6 vs. 93 +/- 13; P < 0.001). Similar results were observed during the iontophoresis of NaNP (P < 0.05). No differences were found among the three groups when the ratio of the forearm:foot response was calculated for both the endothelium-dependent (neuropathic group, 2.25 +/- 0.24; non-neuropathic group, 2.55 +/- 0.35; and control subjects, 2.11 +/- 0.26; P = NS) and endothelium-independent vasodilation (neuropathic group, 1.54 +/- 0.27; non-neuropathic group, 2.08 +/- 0.33; and control subjects, 2.77 +/- 1.03; P = NS). The vasodilatory response, which is related to the C nociceptive fiber action, was reduced at the foot level during iontophoresis of Ach in the neuropathic group. In contrast, no difference was found during the iontophoresis of NaNP at the foot and forearm level and of Ach at the forearm level among all three groups. CONCLUSIONS: In healthy subjects, the endothelial-dependent and endothelial-independent vasodilatation is lower at the foot level when compared to the forearm, and a generalized impairment of the microcirculation in diabetic patients with neuropathy preserves this forearm-foot gradient. These changes may be a contributing factor for the early involvement of the foot with neuropathy when compared to the forearm.

Adult↗
PubMed1998

Effect of growth hormone on fibrinolytic system in rat.

Growth hormone deficiency (GHD) is associated as a risk factor in increased mortality from cardiovascular diseases. Abnormal lipid profile and increased levels of plasminogen activator inhibitor (PAI) and fibrinogen have been noted in GHD patients. Present study was carried out to investigate the effect of growth hormone (GH) on plasminogen activator (PA) activity in heart, levels of PA, PAI, glucose and fibrinogen in plasma and serum lipid profile. Rats were injected 125 mU GH kg-1 body weight subcutaneously daily for one week. PA activity was significantly higher in the heart of GH treated rats as compared to controls. GH treatment decreased plasma glucose and fibrinogen levels significantly. No significant differences were seen in PA, PAI in plasma, triglycerides and total cholesterol in serum of the two groups of rats. A significant increase in high density lipoprotein cholesterol (HDL) occurred in GH treated group resulting into a decrease in LDL/HDL ratio. The results indicate that GH may be beneficial in cardiovascular diseases as it decreases the levels of plasma fibrinogen and increases the level of HDL in blood and also increases the level of PA in heart.

Animals↗
PubMed1997

RNA base-amino acid interaction strengths derived from structures and sequences.

We investigate RNA base-amino acid interactions by counting their contacts in structures and their implicit contacts in various functional sequences where the structures can be assumed to be preserved. These frequencies are cast into equations to extract relative interaction energetics. Previously we used this approach in considering the major groove interactions of DNA, and here we apply it to the more diverse interactions observed in RNA. Structures considered are the three different tRNA synthetase complexes, the U1A spliceosomal protein with an RNA hairpin and the BIV TAR-Tat complex. We use binding data for the base frequencies for the seryl, aspartyl and glutaminyl tRNA-synthetase and U1 RNA-protein complexes. We compare with the previously reported DNA major groove peptide contacts the results for atoms of RNA bases, usually in the major groove. There are strong similarities between the rank orders of interacting bases in the DNA and the RNA cases. The apparent strongest RNA interaction observed is between arginine and guanine which was also one of the strongest DNA interactions. The similar data for base atomic interactions, whether base paired or not, support the importance of strong atomic interactions over local structure considerations, such as groove width and alpha-helicity.

Amino Acid Sequence↗
PubMed1997

Lower extremity macrovascular disease in diabetes.

Lower extremity macrovascular disease is more common and progresses more rapidly in the presence of diabetes and has a characteristic peritibial distribution with sparing of the foot arteries. The biology of the diabetic foot is compromised, thereby making it more susceptible to injury. Hence, compromises in perfusion have a greater significance, warranting an aggressive approach to revascularization.

Arterial Occlusive Diseases↗