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Biomedical subjects

A M Sharma

Publications and source records attributed to A M Sharma.

At least 19 recordsLinked to original sources
PubMed2007

Obesity and the heart: redefinition of the relationship.

Although obesity is an important cardiovascular risk factor, growing evidence shows that obesity is not always related to an unfavourable cardio-metabolic profile or poor cardiac outcomes. Recent studies show that excess fat even in the absence of comorbidities (uncomplicated obesity) can lead to adaptive cardiac morphological and functional changes. Uncomplicated obesity represents a well-defined clinical entity that should be carefully considered and followed up. The existence of metabolically healthy subjects presenting a lower prevalence of cardiac modifications and risk factors strongly suggests that a redefinition of obesity based on regional fat distribution indices like waist-to-hip ratio instead of body mass index is warranted.

Adaptation, Physiological↗
PubMed2006

Chondrocyte deformation induces mitochondrial distortion and heterogeneous intracellular strain fields.

Chondrocyte mechanotransduction is poorly understood but may involve cell deformation and associated distortion of intracellular structures and organelles. This study quantifies the intracellular displacement and strain fields associated with chondrocyte deformation and in particular the distortion of the mitochondria network, which may have a role in mechanotransduction. Isolated articular chondrocytes were compressed in agarose constructs and simultaneously visualised using confocal microscopy. An optimised digital image correlation technique was developed to calculate the local intracellular displacement and strain fields using confocal images of fluorescently labelled mitochondria. The mitochondria formed a dynamic fibrous network or reticulum, which co-localised with microtubules and vimentin intermediate filaments. Cell deformation induced distortion of the mitochondria, which collapsed in the axis of compression with a resulting loss of volume. Compression generated heterogeneous intracellular strain fields indicating mechanical heterogeneity within the cytoplasm. The study provides evidence supporting the potential involvement of mitochondrial deformation in chondrocyte mechanotransduction, possibly involving strain-mediated release of reactive oxygen species. Furthermore the heterogeneous strain fields, which appear to be influenced by intracellular structure and organisation, may generate significant heterogeneity in mechanotransduction behaviour for cells subjected to identical levels of deformation.

Animals↗
PubMed2006

Adipose tissue and circulating endothelial cell specific molecule-1 in human obesity.

Adipocytes produce the endothelial-cell specific molecule-1 (ESM-1), which inhibits leukocyte adhesion and migration through the endothelium. This study investigates ESM-1 expression and regulation in human adipose tissue. Subcutaneous abdominal adipose tissue was obtained from seventy postmenopausal women. Fourteen women subsequently underwent non-pharmacological weight reduction. In vitro experiments were performed on adipocytes isolated from human mammary adipose tissue. We determined gene expression by TaqMan RT-PCR and measured ESM-1 levels in serum and cell culture medium by ELISA. Mature adipocytes produced ESM-1. ESM-1 gene expression was higher in adipocytes than in preadipocytes. Cortisol inhibited ESM-1 gene expression in preadipocytes. Insulin and cortisol inhibited adipocyte ESM-1 production in adipocytes. This inhibitory effect of insulin was attenuated by insulin resistance, as ESM-1 gene expression in subcutaneous adipose tissue was increased in obese, hyperinsulinemic women. In contrast, ESM-1 serum levels were reduced in obese women and inversely correlated to C-reactive protein levels. Five percent weight loss did not markedly change gene expression. Circulating ESM-1 levels increased significantly, albeit modestly. ESM-1 is actively produced by adipocytes. However, since ESM-1 adipocyte gene expression and circulating plasma levels are not correlated, other sources of ESM-1 may be more important. Circulating ESM-1 levels are reduced in the overweight and obese, consistent with the notion that ESM-1 may play some role in obesity-associated vascular disease.

Adipocytes↗
PubMed2006

The effect of oral glucose loads on tissue metabolism during angiotensin II receptor and beta-receptor blockade in obese hypertensive subjects.

AT1 receptor blockers and ACE inhibitors decrease the risk for new onset diabetes mellitus. The phenomenon could be related to a direct angiotensin II effect on tissue metabolism. To address the issue, we recruited eighteen obese hypertensive patients. Patients were randomized to double-blind treatment with either valsartan (n = 8) or atenolol (n = 10) for thirteen weeks. They underwent an oral glucose tolerance test before and during active treatment, while metabolism was monitored through subcutaneous and intramuscular microdialysis and indirect calorimetry. After glucose ingestion, venous glucose and insulin concentrations increased rapidly while systemic free fatty acid concentrations were suppressed. Dialysate glucose and lactate concentrations increased briskly in adipose tissue and in skeletal muscle. Dialysate glycerol decreased profoundly in both tissues. Respiratory quotient increased markedly after glucose ingestion. These responses were identical at baseline and during active treatment either drug. We conclude that AT1 receptor blockade in obese hypertensive patients has no effect on interstitial glucose supply, lipolysis, and substrate oxidation. One possible explanation is that angiotensin II levels in obese hypertensives are not sufficient to elicit the metabolic changes that have been observed after direct angiotensin II application. The exact mechanism by which inhibition of the renin-angiotensin-aldosterone system decreases the diabetes risk remains unresolved and requires further study.

Adipose Tissue↗
PubMed2006

Reduced left ventricular mass after treatment of obese patients with sibutramine: An echocardiographic multicentre study.

AIM: In obesity, left ventricular hypertrophy is frequently observed, especially in the presence of hypertension. Following body weight reduction, the left ventricular mass (LVM) is reduced. It is not known to which extent this occurs after treatment with sibutramine. METHODS: In this multicentre trial, 195 male and female patients (18-65 years of age, body mass index 30-40 kg/m2) were treated for 12 weeks with either 15 mg/day sibutramine or placebo. They were advised to follow mildly hypocaloric reducing diets. Exclusion criteria were blood pressure values >180/110 mmHg and tachycardia (heart rate > or =100 beats/min). Echocardiography in M-mode was performed to determine LVM as well as systolic function. RESULTS: Body weight was reduced by 6.9 +/- 0.3 kg under sibutramine and by 2.1 +/- 0.6 kg under placebo; body fat was reduced by 5.2 +/- 0.4 kg and 1.6 +/- 0.7 kg respectively. In the sibutramine group, LVM was reduced by 10.9 +/- 24.2 g; LVM indexed for body surface area was reduced by 2.3 +/- 11.8 g/m2 and LVM indexed for body height was reduced by 2.5 +/- 6.0 g/m(2.7). In the placebo group, LVM and LVM indices were not significantly changed. Changes in LVM correlated with reductions in body weight and initial LVM but not with changes in blood pressure or heart rate. CONCLUSIONS: After 3 months of treatment with sibutramine, obese patients lost about three times as much of body weight and LVM than patients treated with placebo. Therefore, sibutramine may be recommended not only to reduce body weight but also to obtain a regression of the LVM in obese patients with and without hypertension.

Adult↗
PubMed2005

Obesity, hypertension and insulin resistance.

Being overweight or obese has become highly prevalent in Western countries and are rapidly reaching epidemic proportions in the developing world. Obesity-related disorders, such as hypertension and diabetes, are also increasing at an alarming rate. The relationship between obesity, hypertension and insulin resistance is well recognised, but the molecular mechanisms involved remain relatively poorly understood. Adipose tissue plays a key role in the pathogenesis of the metabolic syndrome. It serves as an important source of pro-inflammatory molecules, including leptin, tumour necrosis factor alpha, angiotensin II and interleukin-6, as well as anti-inflammatory molecules, such as adiponectin. Knowledge of how these adipose tissue-derived factors influence metabolic and cardiovascular disease has recently expanded. Leptin is now considered to play a key role in the elevation of sympathetic activity commonly found in obese, hypertensive patients, and decreased secretion of adiponectin appears to be an important predictor of diabetes. The ectopic storage of excess fat in skeletal muscle, liver or pancreas, due to the decreased capacity of adipose tissue to scavenge excess calories, may also play a role in the development of insulin resistance and type 2 diabetes. Overall, continuing research into the relationship between adipose-tissue biology and metabolic abnormalities may lead to a better understanding of the molecular mechanisms underlying the relationship between obesity and cardiovascular disease, and ultimately provide alternative treatments for the control of potentially life-threatening conditions.

Female↗
PubMed2005

Influence of Sibutramine on blood pressure: evidence from placebo-controlled trials.

OBJECTIVE: Sibutramine, a serotonin and norepinephrine transporter inhibitor, is widely used as an adjunctive obesity treatment. There have been concerns that norepinephrine reuptake inhibition with sibutramine could exacerbate arterial hypertension. DESIGN: Combined analysis of two placebo-controlled trials. SUBJECTS: The combined data set consisted of 1336 patients. Of these patients, 966 were randomized to sibutramine and 370 were randomized to placebo. MEASUREMENTS: Body weight, blood pressure, heart rate (HR). RESULTS: Sibutramine reduced body weight regardless of basal blood pressure. In the complete set of patients, systolic blood pressure did not change with either intervention over the 48-week period (-0.1+/-15.5 mmHg with sibutramine, -0.2+/-15.2 mmHg with placebo, P=0.9). The change in diastolic blood pressure over the 48 week period was 0.3+/-9.5 mmHg with sibutramine and -0.8+/-9.2 mmHg with placebo (P=0.049). The blood pressure response was not exacerbated in patients with grade 1 or 2 hypertension or in patients with isolated systolic hypertension. Sibutramine treatment caused a slight increase in supine HR that was sustained throughout the studies. CONCLUSIONS: Sibutramine treatment is unlikely to elicit a critical increase in blood pressure even in hypertensive patients. However, blood pressure and HR should be monitored closely. In patients who experience a clinically significant and sustained increase in blood pressure, the drug should probably be discontinued.

Adolescent↗
PubMed2005

The Third International Symposium on Obesity and Hypertension ISOH'03: 'Genetics and Molecular Mechanisms' (October 23-25, 2003, Berlin Germany).

The Third International Symposium on Obesity and Hypertension (ISOH'03) was held on 23-25, October 2003 at the Max Delbruck Center for Molecular Medicine in Berlin-Buch, Germany. The meeting, which consisted largely of invited lectures, presented a state-of-the-art overview of the genetic and molecular mechanisms that link obesity and hypertension. The over 40 oral presentations were supplemented by around 90 poster presentations from 34 countries. The meeting was attended by around 250 participants from 54 countries. This paper briefly reviews the contents of the invited lectures presented at this meeting covering topics ranging from genetics, molecular mechanisms, pathophysiology, cardiovascular risk, to the management of patients with obesity-related hypertension. Stimulated by the continuing success of these Symposia, the organizers are currently planning to hold a Fourth International Symposium on Obesity and Hypertension (ISOH'05) in Berlin: a tentative date for this meeting has been set for 27-29, October 2005.

Berlin↗
PubMed2005

Telmisartan in patients with mild/moderate hypertension and chronic kidney disease.

AIMS: This study assessed the clinical efficacy and safety of telmisartan, an angiotensin II receptor blocker with a long terminal elimination half-life and almost exclusively excreted in bile, in patients with varying severity of chronic kidney disease (CKD). PATIENTS AND METHODS: Adults with diastolic blood pressure (DBP) 90 - 109 mmHg and stable CKD were enrolled: mild/moderate (creatinine clearance (CrCl) 30 - 74 ml/ min/1.73 m2), severe (CrCl < 30 ml/min/1.73 m2) or requiring maintenance hemodialysis. A two- to four-week single-blind, placebo run-in period preceded once-daily telmisartan 40 mg administration for four weeks. Telmisartan 80 mg was given after four- or eight-week treatment ifDBP > or = 85 mmHg. After 12-week treatment, trough DBP/systolic blood pressure (SBP), DBP and SBP control rates, renal function and tolerability were recorded. RESULTS: Mean changes in DBP/SBP were 10.5/-10.7 mmHg for mild/moderate CKD (n = 27), -11.2/-14.9 mmHg for severe CKD (n = 27) and -15.0/-21.1 mmHg for hemodialysis patients (n = 28). DBP control rates (< 90 mmHg)/SBP responses (< 140 mmHg or > 10 mmHg reduction) occurred in 59.3%/66.7%, 63.0%/70.4% and 71.4%/92.9% of mild/moderate CKD, severe CKD and hemodialysis patients, respectively. Incidences of drug-related adverse events were low, and all were known adverse events of telmisartan and common to other angiotensin II receptor blockers. At the end of treatment, a decrease in 24-h urine creatinine occurred in 5/53 (9.4%) patients. Two patients discontinued treatment prematurely due to the worsening of CKD and one due to aggravated proteinuria. CONCLUSION: Once-daily telmisartan provided effective and well-tolerated treatment of mild/moderate hypertension in CKD patients, with no worsening of renal function.

Administration, Oral↗
PubMed2004

[Arterial hypertension in obese patients. Rationale for a prospective medical care study in the family doctor's practice].

Patients with high blood pressure are often overweight or even obese. Conversely, some 43% of overweight and obese patients suffer from hypertension. Diabetes (16.7%), coronary heart disease (15.0%) and nephropathy (7.8%) are common additional findings. The cardiac risk in these patients is thus appreciably elevated. Currently, a prospective medical care study "Best practice with irbesartan in overweight and obese patients" (BIG) - is being conducted throughout Germany. In this study obese hypertensive patients of general practitioners are receiving the AT1 blocker irbesartan, as monotherapy or in fixed combination with the diuretic hydrochlorothiazide over a period of 3 months. Obese patients and nonobese patients are compared with regard to the following variables: drug utilization, blood pressure decrease, responder rates, normalization rates, decrease in the number of patients with (micro)albuminurea, changes in patient risk profile (e.g. after SCORE), and tolerability. The study is expected to provide new information on the efficacy, tolerability and safety of irbesartan in regard to pressure reduction and its protective effect on the kidneys and heart in overweight patients.

Albuminuria↗
PubMed2004

Patterns of antihypertensive drug utilization in primary care.

BACKGROUND: In the treatment of hypertension, physicians' attitudes and practice patterns are receiving increased attention as contributors to poor blood pressure (BP) control. Thus, current use of antihypertensive drugs in primary care was analyzed and the association with selected physician and patient characteristics was assessed. METHODS: The Hypertension and Diabetes Risk Screening and Awareness (HYDRA) study is a cross-sectional point prevalence study of 45,125 primary care attendees recruited from a representative nationwide sample of 1912 primary care practices in Germany. Prescription frequencies of the various antihypertensive drugs in the individual patients were recorded by the physicians using standardized questionnaires. We assessed the association of patient variables [age, gender; co-morbidities such as diabetes, nephropathy or coronary heart disease (CHD)] and physician variables (general practitioner vs internist, guideline adherence, etc.) with drug treatment intensity and prescription patterns. RESULTS: Of all 43,549 patients for whom a physician diagnosis on hypertension or diabetes was available, 17,485 (40.1%) had hypertension. Of these hypertensive patients, 1647 (9.4%) received no treatment at all, 1191 (6.8%) received non-pharmacological measures only, and 14,647 (83.8%) were given one or more antihypertensive drugs. Drug treatment rates were lower in young patients (16-40 years: 57.4%). BP control was poor: 70.6% of all patients were not normalized, i.e., had BP >/=140/90 mmHg. Antihypertensive treatment was generally intensified with increasing age, or if complications or comorbidities were present. The use of the different drug classes was rather uniform across the various patient subgroups (e.g., by age and gender). Individualized treatment with regard to co-morbidities as recommended in guidelines was not the rule. Adherence to guidelines as self-reported by physicians as well as other physician characteristics (region, training etc.) did not result in more differentiated prescription pattern. CONCLUSIONS: Despite the broad armamentarium of drug treatment options, physicians in primary care did not treat hypertension aggressively enough. Treatment was only intensified at a late stage, after complications had occurred. Treatment should be more differentiated in terms of coexisting morbidities such as diabetes, nephropathy, or CHD.

Adolescent↗
PubMed2004

Recognition and management of overweight and obesity in primary care in Germany.

BACKGROUND: In contrast to the well-documented high prevalence of overweight and obesity in the general population, the prevalence, recognition rates and management by primary care physicians--as the core gatekeeper in the health care system--remains poorly studied. PURPOSE OF THE STUDY: To examine (1) the point prevalence of overweight (BMI 25.0-29.9 kg/m(2)) and obesity (BMI> or =30 kg/m(2)) in primary care patients, (2) prevalence patterns in patients with high-risk constellations (diabetes, hypertension, cardiovascular disease, etc.), (3) doctors' recognition and interventions, as well as patients' use and perceived effectiveness of weight-loss interventions and (4) factors associated with non-treatment. METHODS: Cross-sectional point prevalence study of 45 125 unselected consecutive primary care attendees recruited from a representative nationwide sample of 1912 primary care practices. MEASURES: (1) standardized clinical appraisal of each patient by the physician (diagnostic status and recognition, severity, comorbidity, current and past interventions). (2) Patient self-report questionnaire: height and weight, illness history, past and current treatments and their perceived effectiveness, health attitudes and behaviors. RESULTS: (1) In all, 37.9% of all primary care attendees were overweight, 19.4% obese. (2) Rates for overweight and obesity were highest in patients with diabetes (43.6 and 36.7%) and hypertension (46.1 and 31.3%), followed by patients with cardiovascular disorders. Rates of overweight/obesity increased steadily by the number of comorbid conditions. (3) Doctors' recognition of overweight (20-30%) and obesity (50-65%) was low, patients' actual use of weight control interventions even lower (past 12 months: 8-11%, lifetime: 32-39%). Patient success rates were quite limited. (4) Co- and multimorbidity in particular as well as other patient and illness variables were identified as predictors for recognition, but prediction of patients' actual use of weight loss interventions was limited. CONCLUSIONS: Primary care management of overweight and obesity is largely deficient, predominantly due to four interrelated factors: doctors' poor recognition of patients' weight status, doctors' inefficient efforts at intervention, patients' poor acceptance of such interventions and dissatisfaction with existing life-style modification strategies.

Age Distribution↗
PubMed2004

Moxonidine in the treatment of overweight and obese patients with the metabolic syndrome: a postmarketing surveillance study.

Moxonidine is a centrally active imidazoline receptor agonist that effectively lowers blood pressure and has been shown to have beneficial effects on lipid and carbohydrate metabolism. We assessed the efficacy of moxonidine in a postmarketing surveillance study (CAMUS) conducted in 772 practices in Germany, documenting 4005 patients with hypertension, who were overweight and/or suffered from metabolic syndrome. Patients were treated with moxonidine (Cynt) for the first time following the baseline visit for 8 weeks. Mean blood pressure decreased from 168/97 to 141/83 mmHg for all patients and from 168/96 to 141/83 mmHg for patients with metabolic syndrome. Blood pressure reduction was particularly pronounced in patients with severe hypertension at baseline. The response rate (DBP< or =90 mmHg or reduction > or =10 mmHg) of antihypertensive treatment with moxonidine was 94.0% for all patients and 93.8% for patients with metabolic syndrome. The recommended targets for antihypertensive treatment of the German Diabetes Society/German Hypertension Society were reached by 30.5% of nondiabetics (goal: <140/90 mmHg) and by 3.6% of diabetics (goal: <130/80 mmHg) observed. After 8 weeks of treatment, patients achieved a mean weight loss of 1.4 kg, which was particularly pronounced in obese patients. The rate of patients receiving antihypertensive combination therapy was 81.1% for those with metabolic syndrome, and 63.3% for all other patients. Patients with metabolic syndrome were preferentially treated with ACE inhibitors and diuretics. We conclude that moxonidine effectively reduces blood pressure in patients with metabolic syndrome while simultaneously reducing body weight in obese patients.

Adult↗
PubMed2003

[Aim, design and methods of the "Hypertension and diabetes screening and awareness" -- (HYDRA) study].

Aim of the study is a comprehensive clinical-epidemiological description of the prevalence of arterial hypertension and diabetes among primary care patients along with an assessment of doctor's recognition rates and prescription behaviour. The paper describes methods and design of the study and provides background information on the sampling process, instruments used as well as characteristics of doctors and patients. The study is based on a nationally representative sample of 1,912 primary care doctors and 45,000 patients that attended the doctors' office on the target days. The patients were also characterized by laboratory tests. The first stage of study consisted of a comprehensive description of the doctors' characteristics in terms of psychosocial, qualification- and provider aspects as well as attitudes towards hypertension and diabetes and their management. In the second stage all patients completed a questionnaire to describe their health behaviour and attitudes as well as the treatment history and therapy. In the third stage all patients were characterized by their doctors in terms of their diagnostic status and their past and current interventions.

Adolescent↗