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Biomedical subjects

S Verma

Publications and source records attributed to S Verma.

At least 109 records · Page 6Linked to original sources

Polymeric versus elemental diet as primary treatment in active Crohn's disease: a randomized, double-blind trial.

OBJECTIVE: Enteral feeding is now an established primary therapy for active Crohn's disease. This first-double blind randomized trial was designed to compare the therapeutic efficacy of a polymeric diet (PD) with an elemental diet (ED). METHODS: Patients with active Crohn's disease (Crohn's disease activity index [CDAI] > 150, increased bowel uptake of Tc-HMPAO-labeled leukocytes, and abnormal C-reactive protein [CRP]), were randomized to receive either an ED or a PD. The two preparations were identical except for the nitrogen source, which was amino acid based in ED and intact protein in PD. Enteral feeding was considered successful if clinical remission was achieved as defined by a final CDAI of < or = 150, a reduction in the CDAI by at least 100 points from baseline level, and a normal CRP. RESULTS: Twenty-one patients were enrolled of whom 11 were randomized to PD and 10 to ED. The two groups were comparable at entry. Clinical remission was obtained in eight (80%) patients receiving ED and six (55%) patients receiving PD, p = 0.1. The treatment failed in three and two patients in the PD and ED groups, respectively. Another two patients were intolerant to the feed (PD). Reduction in the CDAI after treatment with ED (359 +/- 67 to 112 +/- 19) was similar to that seen with PD (303 +/- 27 to 97 +/- 11). Similar changes in the CRP were also observed (16 +/- 5 to 4 +/- 1.6) and (62 +/- 20 to 9 +/- 6), respectively. Overall, enteral feeding was successful in 14 patients (63%). CONCLUSIONS: Enteral nutrition is effective in treatment of active Crohn's disease. Differences in nitrogen sources of enteral feeds are not relevant to their therapeutic efficacy, as polymeric and elemental diets are equally effective.

Crohn Disease↗

Differential regulation of leptin transport by the choroid plexus and blood-brain barrier and high affinity transport systems for entry into hypothalamus and across the blood-cerebrospinal fluid barrier.

Leptin is a circulating hormone that controls food intake and energy homeostasis. Little is known about leptin entry into the central nervous system (CNS). The blood-cerebrospinal fluid (CSF) barrier at the choroid plexus and the blood-brain barrier (BBB) at the cerebral endothelium are two major controlling sites for entry of circulating proteins into the brain. In the present study, we characterized leptin transport across the blood-CSF barrier and the BBB by using a brain perfusion model in lean rats. Rapid, high-affinity transport systems mediated leptin uptake by the hypothalamus (KM = 0.2 ng/ml) and across the blood-CSF barrier (KM = 1.1 ng/ml). High affinity in vivo binding of leptin was also detected in the choroid plexus (KD = 2.6 ng/ml). In contrast, low affinity carriers for leptin (KM = 88 to 345 ng/ml) were found at the BBB in the CNS regions outside the hypothalamus (e.g. cerebral cortex, caudate nucleus, hippocampus). Our findings suggest a key role of high affinity leptin transporters in the hypothalamus and choroid plexus in regulating leptin entry into the CNS and CSF under physiological conditions. Low affinity transporters at the BBB outside the hypothalamus could potentially contribute to overall neuropharmacological effects of exogenous leptin.

Animals↗

Normal endothelial function despite insulin resistance in healthy women with the polycystic ovary syndrome.

Women with the polycystic ovarian syndrome (PCOS) carry a number of cardiovascular risk factors, including insulin resistance, lipid abnormalities, and an altered pattern of sex steroid exposure. Noninvasive measurements of endothelial function, which can demonstrate abnormalities well in advance of clinically apparent disease, have not been previously reported in this patient group. We undertook a cross-sectional evaluation of endothelium-dependent and -independent vascular function using brachial artery ultrasound. We studied healthy women with clinical and laboratory evidence of PCOS (n = 18) and age-matched controls (n = 19), not taking any antihypertensive, cholesterol-lowering, or hormonal therapies. Laboratory parameters of insulin resistance, glycemia, cholesterol status, and hormone levels were also measured. Despite marked differences in glucose/insulin ratio [6.1 +/- 1.1 mmol/pmol (PCOS) vs. 9.9 +/- 0.6 (controls)] and free androgen index [11.9 +/- 2.3 (PCOS) vs. 3.7 +/- 0.6 (controls); normal, <5], we did not find evidence of impaired endothelial function in our patients with PCOS. Both endothelium-dependent (8.7 +/- 3.1%) and endothelium-independent (23.2 +/- 3.4%) vascular responses were normal, and practically identical to the responses seen in the control group (endothelium-dependent, 9.0 +/- 0.7; endothelium-independent, 23.0 +/- 1.2%). The PCOS women were more obese, but baseline brachial arterial diameters were not different between groups. There was no correlation between degree of insulin resistance or hyperandrogenism and the brachial response. This group of healthy obese young women with insulin resistance and hyperandrogenism due to PCOS had normal endothelium-dependent and -independent vascular responses compared to age-matched controls. The factors resulting in preservation of these response are unclear and warrant further investigation.

Adult↗

Chronic pain. Sources of late-life pain and risk factors for disability.

The prevalence of pain peaks in middle age and decreases thereafter, according to most epidemiologic studies of complaints of pain. However, this apparent decrease in pain in older adults may be a statistical artifact. Eighty to 85% of persons experience a significant health problem that predisposes them to pain at some time after age 65. With aging, patients experience less frequent head, abdominal, and chest pain and more frequent joint pain. Women are more likely to report musculoskeletal pain and multiple pain sites than men, but there are no gender differences for reports of chest and abdominal pain. Many patients with chronic pain have clinically significant depressive symptoms and low self-reported quality-of-life scores.

Age Distribution↗

Growing problem of methicillin resistant staphylococci--Indian scenario.

In the present study MRSA prevalence increased from 12% in 1992 to 80.83% in 1999. Indian literature shows that MRSA incidence was as low as 6.9% in 1988 and reached to 24% and 32.6% in Vellore and Lucknow in 1994 and was of the same order in Mumbai, Delhi and Bangalore in 1996 and in Rohtak and Mangalore in 1999. However, in some of the centres it was as high as 87%. All the MRSA isolates in India including in the present study were sensitive to vancomycin and resistance to netilmycin appears to be low among MRSA isolates in India. All the MRSA isolates were also found to be sensitive to teicoplanin in the present study. Like in other Indian studies, resistance to cotrimoxazole, erythromycin, gentamicin, other penicillins and cephalosporins appeared to be a common feature for MRSA isolates in the present study.

Animals↗

Somatization.

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Adult↗

Sympathectomy prevents fructose-induced hyperinsulinemia and hypertension.

The fructose-induced hypertensive rat is a widely used model to study the inter-relationship between hyperinsulinemia, insulin resistance and high blood pressure. Evidence suggests that hyperinsulinemia and insulin resistance may be pathogenic in the development of high blood pressure in this model. To determine the contribution of the sympathetic nervous system towards fructose-induced hypertension, the present study examined the effects of chemical sympathectomy (adrenal medullectomy, followed by weekly 6-hydroxydopamine injections) on plasma insulin levels and systolic blood pressure in control and fructose-induced hypertensive rats. Sympathectomy abrogated the development of both hyperinsulinemia and hypertension in fructose hypertensive rats without affecting these parameters in control rats. These data uncover, for the first time, the primacy of the sympathetic nervous system as a mediator of both elevated plasma insulin levels and high blood pressure in rats fed a high fructose diet.

Animals↗

Hematopoietic growth factors signal through the formation of reactive oxygen species.

Hematopoietic growth factors (HGFs) stimulate growth, differentiation, and prevent apoptosis of progenitor cells. Each growth factor has a specific cell surface receptor, which activates both unique and shared signal transduction pathways. We found that several HGFs, including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), steel factor (SF), and thrombopoietin (TPO) induce a rapid increase in reactive oxygen species (ROS) in quiescent cells. In an effort to understand the potential biochemical and biological consequences of increased ROS in these cells, we exposed growth factor-deprived cells to hydrogen peroxide (H2O2) at concentrations that increased intracellular ROS. H2O2 induced a dose-dependent increase in tyrosine phosphorylation, including increased tyrosine phosphorylation of the GM-CSF receptor beta chain (betac), STAT5, and other signaling proteins. H2O2 also induced expression of the early response gene c-FOS, and G1- to S-phase transition, but not S- to G2/M-phase transition of MO7e cells. The cell permeable antioxidant pyrrolidine dithiocarbamate (PDTC) decreased the intracellular levels of ROS and inhibited tyrosine phosphorylation induced by GM-CSF in MO7e cells, suggesting that ROS generation plays an important role in GM-CSF signaling. Consistent with this notion, PDTC and two other antioxidants, N-acetyl cysteine and 2-mercaptoethanol, reduced growth and viability of MO7e cells. These results suggest that generation of ROS in response to HGFs may contribute to downstream signaling events, especially those involving tyrosine phosphorylation.

Acetylcysteine↗

Both CD4(+) T cells and CD8(+) T cells are required for iodine accelerated thyroiditis in NOD mice.

The nonobese diabetic (NOD) mouse, a spontaneous animal model for insulin-dependent diabetes mellitus, displays a tendency in common with human diabetic populations to develop autoimmune thyroiditis although incidence and severity of thyroid lesions vary widely among different colonies around the world. A congenic strain of NOD mice bearing I-Ak on a NOD background (NOD-H2(h4)) has recently been derived and displays a much greater tendency to develop thyroiditis and autoantibodies to mouse thyroglobulin (MTg) although it is free of diabetes. Both thyroid infiltrates and autoantibody formation are accelerated and enhanced in NOD-H2(h4) mice by increased iodine intake. The effect of increased iodine intake on NOD mice themselves has not been directly investigated although a recent study of these animals given high or low doses of iodine showed no follicular destruction unless the mice were first rendered goitrous by iodine deprivation. We found that dietary iodine increased both the incidence and the severity of thyroid lesions in our NOD mice although autoantibodies to MTg were absent. NOD background genes appear to be essential for the development of these lesions, which were maximal after 4 weeks of iodine administration and showed no significant regression when the iodine was stopped. Furthermore, our studies show for the first time that both CD4(+) and CD8(+) T cells are necessary for the development of this accelerated but essentially spontaneous murine thyroid disease.

Animals↗

Kin I kinesins are microtubule-destabilizing enzymes.

Using in vitro assays with purified proteins, we show that XKCM1 and XKIF2, two distinct members of the internal catalytic domain (Kin I) kinesin subfamily, catalytically destabilize microtubules using a novel mechanism. Both XKCM1 and XKIF2 influence microtubule stability by targeting directly to microtubule ends where they induce a destabilizing conformational change. ATP hydrolysis recycles XKCM1/XKIF2 for multiple rounds of action by dissociating a XKCM1/ XKIF2-tubulin dimer complex released upon microtubule depolymerization. These results establish Kin I kinesins as microtubule-destabilizing enzymes, distinguish them mechanistically from kinesin superfamily members that use ATP hydrolysis to translocate along microtubules, and have important implications for the regulation of microtubule dynamics and for the intracellular functions and evolution of the kinesin superfamily.

Animals↗

Association of adult achalasia and alacrima.

Achalasia is the best described motor disorder of the esophagus. Associations with familial glucocorticoid deficiency and alacrima (triple A syndrome) have been described in the pediatric population, but no attention has been paid to the possibility of this association in adults. Tear production was assessed in 20 patients with achalasia and 20 age- and sex-matched controls. Deficient tears were found in four achalasics compared with none among the controls (P < 0.05). This suggests that some variant of the triple A Syndrome (achalasia, alacrima, and adrenocortical insufficiency) may exist in adult patients with achalasia as well.

Adult↗

Psychological and social determinants of women's decisions to undergo genetic counseling and testing for breast cancer.

This study examined the demand for breast cancer genetic testing and counseling among Canadian women diagnosed with breast cancer under the age of 50, together with some of the factors predicting both their intentions to be tested and the degree to which they act on their intentions. Participants were 110 women under the age of 50 and comprised of two groups: 1) women diagnosed with breast cancer (BC, n = 60): and 2) an index group of unaffected women from the general population (GP, n = 50). All participants completed a survey that addressed family history of breast and other cancers, demographic variables, knowledge and attitudes about breast cancer, and genetic testing. Members of the BC group were offered genetic counseling and testing for BRCA1 and BRCA2 free of charge. Overall, 60% of participants indicated they would like the test, and 40% either did not want it or were uncertain. Seventy-two percent of women in the BC group wanted to be tested. Of these, only 49% had actually contacted the genetic counselor about testing at follow-up 3-15 months later. Intention to be tested was associated with presence of breast cancer, greater perceived benefits of testing, fewer perceived 'costs' of testing, and higher levels of concern about the risk of relatives developing breast cancer. Actual arranging to meet with the genetic counselor among women in the BC group was associated with fewer perceived costs of having the test. Results suggest a moderate level of interest in gene testing, though intention to be tested may not translate into actual uptake. Women who do choose to have the test may believe the potential 'costs' of using this new genetic technology to be relatively few. This has implications for genetic counselors in terms of providing balanced and complete information to women considering genetic testing for breast cancer susceptibility.

Adolescent↗