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Biomedical subjects

S Verma

Publications and source records attributed to S Verma.

At least 73 records · Page 4Linked to original sources
PubMed2001

Does better disease-related education improve quality of life? A survey of IBD patients.

The importance of health-related quality of life (HRQOL) assessment in patients with chronic disorders such as inflammatory bowel disease (IBD) is now acknowledged by researchers. Of the many factors that may influence HRQOL, patient knowledge of the condition and disease-related information provision have hitherto not been studied. In all, 250 patients with inactive IBD (UC = 128, CD = 122) were randomly chosen from our IBD clinic. Two sets of questionnaires [initially a standard questionnaire to assess level of disease-related information by a patient information score (PIS), followed by a HRQOL questionnaire] were sent to each patient. In the PIS, a score of 7 or more indicated satisfactory disease-related knowledge and in the HRQOL, a score less than 51 suggested a normal QOL, and a score above 60 significantly impaired QOL. A total of 168 patients (66%) returned both the questionnaires (UC = 91, CD = 77). The mean QOL in patients with UC and CD was 62.2+/-8.3 and 63.9+/-9.5 respectively, (P = NS). 99 patients (59%) had significantly impaired QOL (mean score 65+/-7.6) with only 12 patients (8%), 6 in each group, having a normal QOL. Mean PIS score for the patients was 7.04+/-0.1; 53% of the UC patients and 75% of the CD patients (P = 0.006) were considered well informed (ie, PIS scores of 7 or more). The mean PIS for UC patients was 6.5+/-0.4 vs 7.5+/-0.2 for the CD group (P = 0.001). There was, however, no correlation seen between the QOL and PIS scores, both for UC and CD patients (R = 0.3). In conclusion, most patients with IBD have impaired QOL, despite of having inactive disease. The level of disease-related knowledge appears to be better in patients with CD, although that does not seem to affect QOL.

Adult↗
PubMed2001

Measuring women's preferences for breast cancer treatments and BRCA1/BRCA2 testing.

In establishing decision models in the treatment and prevention of breast cancer, it is important to evaluate patients' preferences for such interventions. The objectives of the present study were: (i) to characterize women's preferences for breast cancer treatments and BRCA1/BRCA2 testing, using the rating scale and standard gamble techniques; and (ii) to identify factors associated with these quality of life indices. Data were collected from women with breast cancer (n = 60), high-risk relatives of women with breast cancer (n = 58), and women in the general population (n = 51). Regardless of group membership, participants favoured treatment and prevention options that involved minimal physical invasiveness. Women with breast cancer rated lumpectomy and radiation treatment more highly than high-risk relatives and women in the general population. Preferences did not differ according to participants' intentions to undergo BRCA testing. Age was the only demographic variable associated with health state preferences. These findings hold implications for the application of patient preferences to clinical decision making.

Attitude↗
PubMed2001

Men's work and family lives in India: the daily organization of time and emotion.

This article examines daily patterns of work and family life for a sample of middle-class men in northern India. One hundred fathers of 8th graders provided information on their hour-to-hour time use and subjective states, by means of the experience sampling method. They reported little time spent on family work but substantial amounts of time with their children and thinking about their families. At their jobs, they reported high levels of attention but more negative emotion. By contrast, the home sphere elicited lower attention, more favorable affect, and more feeling of choice. Unlike for American samples, little relationship was found between experience at work and home, including little influence of men's work emotions on the family in the evening. These findings reflect how strong traditional family roles in India shape men's daily lives.

Adult↗
PubMed2001

Transplantation of cryopreserved cardiomyocytes.

BACKGROUND: The present study examined the survival and rate of contraction of (1) cardiomyocytes cultured from cryopreserved fetal rat myocardium and (2) cryopreserved cultured cardiomyocytes. In addition, the effects of transplantation of cryopreserved fetal cardiomyocytes were evaluated. METHODS: Segments of fetal rat myocardial tissue (0.2, 2.0, and 6.0 mm(3) mince size) and cultured cardiomyocytes were cryopreserved in liquid nitrogen for 1, 2, and 4 weeks. After cryopreservation, the tissue samples and cultured cardiomyocytes were thawed at 37 degrees C and cultured, and cell proliferation and rate of contraction were determined. Cultured cryopreserved (n = 5) and noncryopreserved (control, n = 5) fetal cardiomyocytes were transplanted into the subcutaneous tissue and into a transmural left ventricular free wall scar of Sprague-Dawley rats (n = 3). The survival and rate of contraction of these transplanted cells were also examined. RESULTS: Cryopreservation of cultured fetal cardiomyocytes resulted in viable and functional cardiomyocytes although the cell number and percentage of beating cells were diminished. Survival of cardiomyocytes isolated from cryopreserved fetal myocardium was a function of tissue size before cryopreservation; the lowest survival was recorded in tissues with the largest mince size (6.0 mm(3)). The subcutaneous transplants contracted spontaneously and regularly with an idioventricular rhythm. In addition, the transplanted cardiomyocytes were elongated and formed a myocardium-like pattern with blood vessels present within the contractile tissue. In the transmural left ventricular scar, both control and experimental fetal cardiomyocyte transplants formed myocardium-like tissue. CONCLUSIONS: The present study uncovers the following key observations: (1) cryopreservation of fetal cardiomyocytes and cardiomyocytes isolated from cryopreserved myocardial tissue results in viable and functional cells, (2) cryopreserved fetal cardiomyocytes can be successfully transplanted into subcutaneous and myocardial scar tissue, and (3) improvements in cryopreservation techniques are required to augment the rates of cardiomyocyte survival observed in the study.

Animals↗
PubMed2001

Does adjuvant nutritional support diminish steroid dependency in Crohn disease?

BACKGROUND: Nutritional therapy plays an important role in the management of Crohn disease, particularly during the acute phase. Nutritional supplementation may also prevent relapses during the quiescent phase of Crohn disease, though this aspect has not been widely explored. METHODS: Thirty-three patients with Crohn disease in remission were studied. All had steroid-dependent disease. Patients were randomized to receive either elemental diet (n = 19, EO28 Extra) or polymeric diet (Forticips, n = 14). The supplement was given orally in addition to normal food in an amount to provide 35%-50% of pre-trial total calorie intake. Prednisolone was withdrawn gradually. Patients were followed up for 12 months. Failure was defined as increase in CDAI by 100 points from baseline to >200, inability to withdraw chronic steroid therapy completely, need for surgery or steroid therapy. RESULTS: The nutritional supplement was successful in 14 (43%) patients who remained in remission for 12 months with complete withdrawal of steroids. The response to elemental diet (42%) was similar to that of polymeric diet (43%). Nutrition supplement failed in 13 (39%). Six (18%) patients were intolerant to enteral feeding because of smell and taste problems. Per-protocol analysis of data indicated that the success rate of nutrition supplement in steroid-dependent patients was 52% (14 out of 27 patients). No disease or patient-related factors helped predict the response to nutrition supplement. CONCLUSION: Nutritional supplementation with either an elemental or polymeric diet may provide a safe and effective alternative to chronic steroid therapy in patients with steroid-dependent Crohn disease.

Adult↗
PubMed2001

Pharmacologic insights into the future of trastuzumab.

A combination of factors has been responsible for improvements in cancer survival and cure rates. In addition to new therapies with novel/genetic targets, these include improvements in drug delivery, new schedules/sequencing of drug administration and the identification of combination therapies with greater activity/dose density than existing regimens. The recognition that such criteria can affect treatment outcome has led to their incorporation into clinical trials of new drugs. Furthermore, pharmacokinetic and pharmacodynamic parameters have become increasingly important for the rational selection of dose, administration route and schedule. The humanized monoclonal antibody trastuzumab (Herceptin) has been rationally developed to target the human epidermal growth factor receptor-2 (HER2), which is overexpressed in 20%-30% of breast cancers and is associated with poor prognosis. Trastuzumab when administered i.v. on a weekly schedule either alone or in combination with taxanes, improves survival of women with HER2-positive metastatic breast cancer. Based upon pharmacokinetic considerations, current studies are examining whether trastuzumab can be administered i.v. every three weeks or by the s.c. route. These regimens would have advantages for patients and medical staff in terms of acceptability, ease of administration and, potentially, cost effectiveness. Furthermore, various combinations of trastuzumab and chemotherapeutic agents are being explored with the aim of identifying the optimal combination regimen for clinical use. The rationale for these various studies and the studies themselves are described.

Antibodies, Monoclonal↗
PubMed2001

Chronic bosentan treatment improves renal artery vascular function in diabetes.

OBJECTIVE: Endothelin-1 (ET-1) has been suggested to play an important role in the pathogenesis of diabetes-induced vascular complications. The primary purpose of the present study was to examine the potential beneficial effects of chronic ET receptor blockade (with bosentan) on vascular function in renal arteries from streptozotocin (STZ)-induced diabetic rats. DESIGN: Wistar rats were divided into four groups: control (C), control bosentan-treated (CB), diabetic (D) and diabetic bosentan-treated (DB). Following 10 weeks of bosentan treatment, vascular responses to norepinephrine (NE), ET-1, acetylcholine (ACh) were determined in vascular segments of renal arteries, both with and without the endothelium denuded, according to the following protocol: (1) a cumulative dose-response curve (DRC) to NE in the absence and presence of the nitric oxide synthase (NOS) inhibitor L-NAME (2) cumulative DRC to ET-1 and (3) cumulative DRC to ACh in precontracted arteries. In addition, plasma ET-1 was assayed and ET-1-like immunoreactivity was determined in vascular tissues by immunohistochemistry. RESULTS: The maximum contractile responses to NE and ET-1 were markedly exaggerated in endothelium-intact renal arteries from untreated D rats while ACh responses were preserved. Arteries denuded of endothelium did not exhibit exaggerated responses to NE or ET-1. L-NAME treatment did not affect responses to NE in arteries with or without endothelium. Strikingly, responses to NE and ET-1 (in arteries with endothelium) were completely normalized following long-term bosentan treatment. In addition, plasma ET-1 levels did not differ between C and D groups. However, renal arteries isolated from the D group exhibited increased ET-1-like immunoreactivity (local ET-1 content). CONCLUSION: These data uncover, for the first time, beneficial effects of mixed ETA/ETB receptor blockade on renal artery vascular function in diabetes. Alterations in the production and/or action of ET-1 may have important implications in the development of vascular dysfunction in experimental diabetes.

Acetylcholine↗
PubMed2001

Open-access versus hospital-initiated flexible sigmoidoscopy: a comparative audit of efficacy.

BACKGROUND AND AIMS: There is a continuing demand for the provision of open-access endoscopy services. While open-access gastroscopy is now a well-established practice in most hospitals, open-access flexible sigmoidoscopy (OAS) is not yet available to the same extent. We present our early experience with OAS, a new service provided by our unit. PATIENTS, METHODS AND RESULTS: Over a 12-month period, 255 flexible sigmoidoscopies were carried out (139 OAS and 116 hospital-initiated sigmoidoscopies, HIS). Referral criteria for sigmoidoscopy were similar in both groups, with rectal bleeding and change in bowel habit being the most frequent. RESULTS: The two groups were comparable with regards to age and gender, but patients referred for OAS had symptoms for shorter duration than those referred for HIS (30 +/- 5.6 months v. 101 +/- 28 months, P < 0.00001). The diagnostic yield for OAS was 44% and for HIS 29% (P= 0.01). Significant pathology (colorectal cancer, polyps and newly diagnosed inflammatory bowel disease, colonic strictures) was detected in 31 patients (22%) in the OAS group and 12 patients (10%) in the HIS group (P = 0.02). Six cancers were diagnosed (5 OAS, 1 HIS), all staged Duke A. The waiting times for OAS and HIS were 3.1 +/- 0.3 weeks and 11.4 +/- 1.2 weeks, respectively (P = 0.0001). The diagnostic yield of fibre-optic endoscopy was independent of duration of symptoms, although patients referred for OAS with rectal bleeding and/or diarrhoea had a higher diagnostic yield (55/125, 44%). CONCLUSION: OAS is feasible and effective, with a high diagnostic yield. Such service can usually be provided with minimal added resources.

Adult↗
PubMed2001

Contact leukoderma of the scalp or an unusual variant of vitiligo?

Contact leukoderma due to hair dyes is strongly suspected in patients presenting with depigmented patches sharply localized to the scalp. We describe three patients with a striking pattern of depigmentation, which stopped abruptly at the hair margins. However, no definite correlation with the use of hair dyes could be made in any of them. Our cases represent an unusual pattern of vitiligo of the scalp, which seems to have been previously attributed mainly to hair colorants. Careful examination of the lesions on the scalp may reveal more cases with this pattern.

Adolescent↗
PubMed2001

Arrhythmias in neurofibromatosis. A case report and review of the literature.

Patients with neurofibromatosis have a higher incidence of anatomic cardiac abnormalities. However, there is little data regarding incidence of arrhythmias in this population. It is known that these patients have a higher mortality than the normal population, and it is possible that some deaths may be due to preventable causes such as cardiac arrhythmias. We report a patient with neurofibromatosis who was treated for a refractory seizure disorder for 8 years. However, video/EEG monitoring demonstrated that the patient had recurrent syncopal seizures secondary to sinus node dysfunction. Complete resolution of symptoms occurred after a permanent pacemaker implantation. We believe this is the first reported case of sinus node dysfunction associated with neurofibromatosis.

Adult↗
PubMed2001

Endothelin antagonism uncovers insulin-mediated vasorelaxation in vitro and in vivo.

The endothelial actions of insulin remain an area of intense research because they relate to both insulin sensitivity and vascular tone. Physiological doses of insulin evoke endothelium-dependent vasorelaxation in humans; however, this remains a pharmacological phenomenon in rat aortas. Because insulin may stimulate the divergent production of both nitric oxide and endothelin-1, we hypothesized that the lack of insulin-induced vasorelaxation at low/subthreshold concentrations may be due to the concurrent production of endothelin-1, which in turn serves to inhibit nitric oxide-dependent, insulin-mediated dilation. To investigate this, we studied the effects of subthreshold concentrations of insulin (100 mU/L) on norepinephrine-induced contraction in rat aortas following short-term and long-term endothelin blockade. In addition, the effects of tetrahydrobiopterin inhibition (with diaminohydroxyprimidine) on norepinephrine-induced contraction in the presence of insulin and endothelin receptor blockade were investigated. Subthreshold concentrations of insulin failed to evoke vasorelaxation in rat aortas. Strikingly, short-term endothelin A/B receptor blockade with bosentan (10(-2) mmol/L) uncovered insulin-mediated dilation; the percent maximum contraction and sensitivity of aortas to norepinephrine were attenuated (% maximum relaxation: bosentan+insulin 74+/-4%* versus bosentan 92+/-3%, insulin 107+/-5% P:<0.002; pD(2) values: bosentan+insulin 6.87+/-0.14* versus bosentan 7.40+/-0.15, insulin 7.63+/-0.11, *P:<0.002). This effect was mediated through endothelin A receptors because bosentan and BQ-123 (10(-2) mmol/L) attenuated norepinephrine-induced contraction to a similar degree. In addition, insulin evoked vasorelaxation in aortas isolated from rats after long-term bosentan treatment (100 mg. kg(-1). d(-1), 3 weeks). The component of insulin-mediated vasorelaxation uncovered by endothelin receptor blockade was tetrahydrobiopterin-dependent because it was reversed by diaminohydroxyprimidine. These data demonstrate, for the first time, the functional interaction between insulin, endothelin-1, and tetrahydrobiopterin in modulating vascular tone in rat aortas in vitro and in vivo.

Acetylcholine↗
PubMed2001

Augmentation of endothelial function by endothelin antagonism in human saphenous vein conduits.

OBJECT: Cerebral revascularization with saphenous vein (SV) conduits is used in the management of hard-to-treat lesions that require deliberate arterial occlusion and in selected patients with occlusive vascular disease. Endothelial dysfunction is thought to contribute to acute perioperative vasospasm and chronic graft atherosclerosis. In the present study the authors examined the contribution of the potent vasoconstrictor endothelin-1 (ET-1) to endothelial dysfunction in human SVs. METHODS: The effects of an ET(A/B) receptor antagonist (bosentan), an ET(A) receptor antagonist (BQ-123), and an ET(B) receptor antagonist (BQ-788) on in vitro endothelium-dependent and -independent responses were studied in human SVs. Vascular segments were obtained in 34 patients who had undergone revascularization procedures, and isometric dose-response curves (DRCs) were constructed using the isolated tissue bath procedure as follows: 1) cumulative DRCs to norepinephrine; and 2) DRCs to acetylcholine (ACh) and sodium nitroprusside in the absence and presence of bosentan, BQ-123, or BQ-788. Maximal vasodilatory responses and sensitivity were compared between groups. In the presence of bosentan (Experiment 1) and BQ-123 or BQ-788 (Experiment 2), ACh responses were significantly augmented (percent maximum relaxation values: 7+/-2 [control] compared with 17+/-3 [bosentan], p < 0.002 [Experiment 1]; and 12+/-2 [control] compared with 29+/-2 [BQ-123] and 25+/-2 [BQ-788], p < 0.003 and p < 0.002, respectively [Experiment 2]). The sensitivity of SVs to ACh was unaffected by treatment. These beneficial effects were specific for the endothelium. CONCLUSIONS: Blockade of ET receptors significantly improves endothelial function in SVs. Furthermore, these effects appear to be independently and maximally mediated by antagonism of either ET(A) or ET(B) receptors. Interventions aimed at improving endothelial function may serve to counter perioperative vasospasm and impede atherosclerosis in SVs used for revascularization procedures.

Aged↗
PubMed2001

Improvement of endothelial function in insulin-resistant carotid arteries treated with pravastatin.

OBJECT: Insulin resistance and hypertension are independent risk factors for stroke. Endothelial dysfunction in response to risk factors and carotid artery (CA) disease are important in the pathogenesis of stroke. Pravastatin may have cholesterol-independent pleiotropic effects. In the present study the authors examined the effects of short-course pravastatin treatment on endothelial function in CAs obtained in control and insulin-resistant rats with fructose-induced hypertension. METHODS: Thirty rats were divided into two experimental groups, in which 14 were fed a regular diet and 16 were fed a fructose-enriched diet for 3 weeks. The rats were then divided into four groups: control, pravastatin-treated control, fructose-fed, and pravastatin-treated fructose-fed. Pravastatin was administered (20 mg/kg/day) for 2 weeks. Excretion of the urinary nitric oxide (NO) metabolite nitrite (NO2-) was also assayed. The CAs from all rats were subsequently removed and assessed for endothelium-dependent and -independent vascular reactivity in vitro. The rats in the fructose-fed group were insulin resistant, hyperinsulinemic, and hypertensive relative to the rats in the control and pravastatin-treated control groups and exhibited diminished endothelium-dependent vasomotion and urinary NO2- excretion (p < 0.05), with preserved endothelium-independent vasomotion. Strikingly, pravastatin treatment restored endothelium-dependent vasomotion and urinary NO2- excretion in rats in the fructose-fed pravastatin-treated relative to the fructose-fed group (p < 0.05). CONCLUSIONS: The authors report, for the first time, that pravastatin restores endothelial function in CAs from insulin-resistant rats with fructose-induced hypertension. These beneficial effects were ascribed to direct, cholesterol-independent vascular effects of pravastatin and are likely the result of augmentation of NO production. These data provide impetus for further investigation of nonlipid-lowering indications for pravastatin therapy in the prevention and treatment of CA disease.

Animals↗
PubMed2001

What drugs are our frail elderly patients taking? Do drugs they take or fail to take put them at increased risk of interactions and inappropriate medication use?

OBJECTIVE: To determine whether there were discrepancies between what medications frail elderly outpatients took and what physicians thought they took and whether discrepancies put patients at risk of taking inappropriate drugs and of increasing the potential for drug interactions. DESIGN: Case series. SETTING: Day Hospital Program at St Mary's of the Lake Hospital in Kingston, Ont. PARTICIPANTS: One hundred twenty community-living elderly patients attending the Day Hospital Program in 1998. Three patients and two family physicians declined to participate. MAIN OUTCOME MEASURES: Lists of medications being taken by patients compared with lists of medications in physicians' charts. Category according to explicit criteria that each drug fell into and risk of drug interactions as determined by the Clinidata Drug Interaction Program. RESULTS: Of the 120 patients, 115 had at least one discrepancy between their lists of medications and their physicians' lists. Of the 1390 medications on the lists, 521 (37%) were being taken by patients without their doctors' knowledge, 82 (6%) were not being taken by patients when doctors thought they were, and 133 (10%) were on both patients' and their doctors' lists but with dosages or frequency of administration that were different. More potential drug interactions were identified on patients' lists than on physicians' lists. No increase in risk of inappropriate drug use was identified. CONCLUSION: Family physicians are often unaware of all the medications their patients are actually taking. Medications used by patients without physicians' knowledge increase the likelihood of drug interactions. Family physicians should look at and inquire about all medications, including over-the-counter drugs, their patients are actually taking.

Aged↗
PubMed2000

Phosphorylation of the pro-apoptotic protein BIK: mapping of phosphorylation sites and effect on apoptosis.

BIK is a pro-apoptotic BCL-2 family member and is the founding member of a subfamily of pro-apoptotic proteins known as "BH3-alone" proteins. Ectopic expression of BIK induces apoptosis in variety of mammalian cells. BIK complexes with various anti-apoptotic BCL-2 family proteins such as adenovirus E1B-19K and BCL-2 via the BH3 domain. However, the heterodimerization activity of BIK alone is insufficient for its apoptotic activity. Previous studies have shown that phosphorylation regulates the functional activity of both anti-apoptotic and pro-apoptotic members of the BCL-2 family. Here, we have examined phosphorylation of BIK and its effect on the apoptotic activity of BIK. We show that BIK exists as a phosphoprotein and is phosphorylated at residues 33 (threonine) and 35 (serine). Mutation of the phosphorylation sites, in which the Thr and Ser residues were changed to alanine residues, reduced the apoptotic activity of BIK without significantly affecting its ability to heterodimerize with BCL-2. Our results suggest that phosphorylation of BIK is required for eliciting efficient apoptotic activity. Partial purification of the protein kinase from HeLa cell cytoplasmic extracts suggest that BIK may be phosphorylated by a casein kinase II-related enzyme.

Apoptosis↗