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Biomedical subjects

M A Weber

Publications and source records attributed to M A Weber.

At least 37 records · Page 2Linked to original sources
PubMed2001

Contrasting clinical properties and exercise responses in obese and lean hypertensive patients.

OBJECTIVES: We sought to test whether the differences in activity of the renin-angiotensin and sympathetic nervous systems at rest or during exercise can explain the differing cardiovascular properties and outcomes of lean and obese hypertensive patients. BACKGROUND: Although lean hypertensive patients have fewer metabolic abnormalities than obese hypertensive patients, paradoxically they appear to have a poorer cardiovascular prognosis. METHODS: To evaluate the heightened risks in lean hypertensive patients, this study compared metabolic, neuroendocrine and cardiovascular characteristics at rest and during a standardized treadmill protocol in obese (body mass index [BMI] = 32.5 +/- 0.3 kg/m2, n = 55) and lean (BMI = 24.3 +/- 0.2 kg/m2, n = 66) hypertensive patients. Normotensive obese (n = 21) and lean (n = 55) volunteers served as control subjects. RESULTS: Compared with the lean normotensive subjects, the lean and obese hypertensive patients had greater left ventricular mass index (LVMI) values, but on multivariate analysis, LVMI correlated with plasma renin activity (p < 0.001) and plasma norepinephrine (PNE) (p < 0.01) in the lean but not the obese hypertensive patients. Arterial compliance (stroke volume/pulse pressure ratio) was reduced in the lean hypertensive patients, in whom it correlated (p = 0.033) with PNE. The PNE rose less (22%) in the obese than in the lean (55%) hypertensive patients in response to standing (p < 0.05). Likewise, during treadmill exercise, there were lesser increases in renin (65% vs. 145%, p < 0.01) and epinephrine (200% vs. 500%, p < 0.05) in the obese hypertensive patients. These changes were also less in obese patients than in lean control subjects, indicating attenuated neurohormonal responses to stress in obesity. CONCLUSIONS: Compared with obese hypertensive patients, cardiovascular properties in lean hypertensive patients are more dependent on catecholamines and the renin system. The different neuroendocrine responses to dynamic stimuli in lean and obese patients also might help to explain the disparity in their cardiovascular outcomes.

Adult↗
PubMed2001

A new chronotherapeutic oral drug absorption system for verapamil optimizes blood pressure control in the morning.

A novel verapamil chronotherapeutic oral drug absorption system (CODAS-Verapamil) designed for bedtime dosing and with controlled onset and extended-release properties was evaluated in 257 patients with mild-to-moderate essential hypertension in an 8-week, double-blind, placebo-controlled trial. After bedtime dosing (9 PM to 11 PM, this delivery system delays drug release for 4 to 5 h, and provides the highest concentrations of verapamil between 6 AM and noon. The study results showed that CODAS-verapamil produced its greatest antihypertensive effect during this morning period (6 AM to 12 noon) and also provided effective trough diastolic blood pressure reductions at 200, 300, and 400 mg. Significant trough systolic blood pressure reductions were achieved only with the 300- and 400-mg doses. The nighttime dosing regimen was not associated with excessive blood pressure (BP) reductions during the sleeping hours, when the antihypertensive effect was generally slightly less than that of the 24-h mean reduction. The CODAS-verapamil provides enhanced BP reduction during the morning period when compared with other time intervals of the 24-h dosing period.

Absorption↗
PubMed2001

Efficacy of candesartan cilexetil as add-on therapy in hypertensive patients uncontrolled on background therapy: a clinical experience trial. ACTION Study Investigators.

A large-scale, 8-week, open-label, clinical experience trial evaluated the efficacy of the angiotensin II receptor (AT1 subtype) blocker candesartan cilexetil (16 to 32 mg once daily) either alone or as add-on therapy in 6465 hypertensive patients. The study population was 52% female and 16% African American with a mean age of 58 years. It included 5,446 patients who had essential hypertension (HBP) and 1,014 patients who had isolated systolic hypertension (ISH). These patients had either untreated or uncontrolled hypertension (systolic blood pressure [SBP] 140 to 179 mm Hg or diastolic blood pressure [DBP] 90 to 109 mm Hg inclusive at baseline) despite a variety of antihypertensive medications including diuretics, calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, and alpha- or beta-blockers, either singly or in combination. The mean baseline blood pressure for the HBP group was 156/97 mm Hg. Candesartan cilexetil as monotherapy (in 51% of HBP patients) reduced mean SBP/DBP by 18.7/ 13.1 mm Hg. As add-on therapy (in 49% of HBP patients) to various background therapies, candesartan cilexetil consistently reduced mean SBP/DBP further, irrespective of the background therapy: diuretics (17.8/11.3 mm Hg), calcium antagonists (16.6/11.2 mm Hg), beta-blockers (16.5/ 10.4 mm Hg), ACE inhibitors (15.3/10.0 mm Hg), alpha-blockers (16.4/10.4 mm Hg). The mean baseline blood pressure for the ISH group was 158/81 mm Hg. Candesartan cilexetil, as monotherapy (in 34% of ISH patients), reduced SBP/DBP by 17.0/4.4 mm Hg. As add-on therapy (in 66% of ISH patients) to various background therapies, candesartan cilexetil consistently reduced mean SBP/DBP further, irrespective of the background therapy: diuretics (17.4/5.1 mm Hg), calcium antagonists (15.6/3.6 mm Hg), beta-blockers (14.0/4.8 mm Hg), ACE inhibitors (13.4/4.3 mm Hg), and alpha-blockers (11.6/4.5 mm Hg). The further blood pressure lowering effects of candesartan cilexetil as add-on therapy were seen regardless of age, sex, and race. Overall, 6.8% of the 6465 patients withdrew because of adverse events, most commonly headache (6.3%) and dizziness (5.0%). Orthostatic hypotension was infrequent; 0.2% with candesartan cilexetil alone, and 0.8% with candesartan cilexetil as add-on therapy. Thus, candesartan cilexetil either alone or as add-on therapy was highly effective for the control of systolic or diastolic hypertension regardless of demographic background when used in typical clinical practice settings.

Adult↗
PubMed2001

Rationalizing the treatment of hypertension.

Management of hypertension in this country is confounded by continual changes in recommended target blood pressure (BP) goals and a nonhomogeneous patient population who have a variety of demographic and clinical characteristics that influence treatment. This paper focuses on three major elements in managing hypertension: BP and the importance of reducing it to acceptably low levels; concomitant risk factors or cardiovascular and renal target involvement; and drug therapy that may confer prognostic advantages beyond those predicted by BP effects.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Common femoral artery ligation and local debridement: a safe treatment for infected femoral artery pseudoaneurysms.

PURPOSE: The management of infected femoral artery pseudoaneurysms (IFAPs) is difficult and controversial. Use of synthetic or autologous conduit during arterial revascularization in these cases is complicated by the presence of sepsis and unavailability of autologous venous conduit. We present the results of common femoral artery (CFA) ligation and local drainage with debridement for the treatment of IFAP. METHODS: A retrospective chart review of six consecutive patients from 1995 to 1999 who presented with IFAP from intravenous drug abuse was performed. Inpatient records, anesthesia records, and outpatient clinic charts were reviewed. All patients were men with right-sided lesions. All six patients abused heroin, and five (83%) abused heroin and cocaine. All six patients had a duplex ultrasound scan, and five (83%) patients had a digital subtraction angiogram to confirm the clinical diagnosis. Proximal vascular control was achieved retroperitoneally through an oblique suprainguinal incision. After vascular isolation and test clamping of the distal external iliac artery (EIA), the pedal pulses were examined with continuous wave Doppler scan. If a Doppler signal was present, this was followed with CFA ligation and local drainage and debridement of the IFAP. RESULTS: Pain at injection site and fever with chills were present in five (83%) and three (50%) patients, respectively. A pulsatile groin mass and thigh or leg edema were present in five (83%) patients. Three patients (50%) had a palpable pedal pulse, and all six had a Doppler signal over a pedal artery at presentation. The mean white cell count was 15.6 thousand per cubic millimeter (range, 9.2-19.3). All patients had a Doppler signal over a pedal artery after distal EIA/CFA test occlusion and ligation. None of the patients required an amputation, and all six patients regained their preoperative ambulatory status. The mean follow-up period was 25 months. Two patients had mild claudication (5-6 blocks) at 18 months and 2 years after surgery. All six patients received drug rehabilitation, but they admitted to drug abuse after surgery and rehabilitation. CONCLUSION: CFA ligation and local debridement are safe treatment modalities for IFAP, if there is an intraoperative Doppler signal over a pedal artery during test occlusion of the distal EIA/CFA. CFA ligation avoids the use and therefore the risk of synthetic conduit infection, because there is a high incidence of postoperative drug injection despite aggressive drug rehabilitation.

Adult↗
PubMed2001

One-year study of felodipine or placebo for stage 1 isolated systolic hypertension.

Asubstantial number of older hypertensive patients have stage 1 isolated systolic hypertension (systolic blood pressure between 140 and 159 mm Hg and diastolic blood pressure <90 mm Hg), but there are currently no data showing that drug treatment is effective, safe, and/or beneficial. To compare the effects of active treatment compared with placebo on blood pressure, left ventricular hypertrophy, and quality of life among older stage 1 isolated systolic hypertensive patients, a randomized, double-blind, parallel-group, multicenter clinical trial comparing felodipine (2.5, 5, or 10 mg once daily) and matching placebo was performed in 171 patients (49% male, average age 66+/-7 years, with 49% white and 30% Hispanic) with a baseline blood pressure of 149+/-7/83+/-6 mm Hg. During 52 weeks of treatment, patients randomized to active treatment achieved significantly lower blood pressures (137.0+/-11.7/80.2+/-7.6 mm Hg for extended-release felodipine versus 147.5+/-16.0/83.5+/-9.7 mm Hg for placebo, P<0.01 for each), a reduced incidence of left ventricular hypertrophy (7% for extended release felodipine versus 24% for placebo, P<0.04), and improved quality of life (change in Psychological General Well-Being index, 3.0+/-6.8 for extended-release felodipine versus -0.8+/-10.3 for placebo, P<0.01) versus baseline. There were no clinically significant differences between treatments in tolerability or adverse effects. Stage 1 isolated systolic hypertension can be effectively and safely treated pharmacologically. Treatment reduced progression to the higher stages of hypertension, reduced the incidence of left ventricular hypertrophy, and improved an overall measure of the quality of life. Larger and longer studies will be needed to document any long-term reduction in cardiovascular event rates associated with treating stage 1 systolic hypertension.

Aged↗
PubMed2001

Hypophosphatemia associated with hypovitaminosis-D in Speke's gazelles (Gazella spekei).

Two juvenile male Speke's gazelles (Gazella spekei) at the St. Louis Zoo showed poor body condition, slowed growth, hunched stance, rough hair coat, and profound hypophosphatemia. The first gazelle was treated with parenteral phosphorous supplements but continued to deteriorate clinically and was euthanatized. The second gazelle had serum 25-hydroxyvitamin D levels of 0 nmol/L and was treated with i.m. injections of vitamin D. It died shortly after starting therapy. The only significant necropsy finding was multiple rib fractures in various stages of healing. Hypovitaminosis D has been confirmed in multiple Speke's gazelles in this collection, indicating possible deficiencies in the diet or in the amount of ultraviolet light available to the gazelles.

Animals↗
PubMed2000

Implications of a health lifestyle and medication analysis for improving hypertension control.

BACKGROUND: National Health and Nutritional Examination surveys have documented poor rates of hypertension treatment and control, leading to preventable morbidity and mortality. OBJECTIVES: To examine covariation in the medication and health lifestyle beliefs and behaviors of persons with hypertension to identify and profile distinct subgroups of patients. METHODS: A sample of 727 patients with hypertension, weighted to match the 1992 National Health Interview Survey age and sex distribution of patients with hypertension, was interviewed by telephone about their beliefs and behaviors regarding hypertension and its management. Cluster analysis of key variables was used to identify 4 patient types. RESULTS: Subgroups differed significantly. Group A members use an effective mix of medication and health lifestyle regimens to control blood pressure. Group B members are most likely to depend on medication and have high adherence rates. Yet they also have high rates of smoking (29%) and alcohol use (average, 104 times per year) and are less likely to exercise regularly. Group C members are most likely to forget to take medication, are likely to be obese, and find it most difficult to comply with lifestyle changes (except for very low rates of smoking and alcohol use). Group D members are least likely to take medication, most likely to change or stop medication without consulting their physician (20%), most likely to smoke (40%), and least likely to control diet (29%). Group A and B members have better health outcomes than group C and D members. CONCLUSIONS: Optimal management strategies are likely to differ for the 4 patient types. Further research should be conducted to validate these findings on a separate sample and to devise and test tailored management algorithms for hypertension compliance and control.

Adult↗
PubMed2000

A novel insulin mimetic without a proliferative effect on vascular smooth muscle cells.

BACKGROUND: Insulin induces vascular smooth muscle cell (VSMC) proliferation, which is an important step in the atherosclerotic process. Recently, a nonpeptidyl fungal metabolite originally referred to as L-783,281, but also known as demethylasterriquinone B-1 (DMAQB-1), was found to have hypoglycemic activity in diabetic mice through interaction with the intracellular beta subunit of the insulin receptor. This study was designed to determine whether DMAQB-1 has an insulin-like proliferative effect on human infragenicular VSMCs. METHODS: Human infragenicular VSMCs were isolated from diabetic patients undergoing amputations. DMAQB-1 cell culture dose response was measured in both serum-free media and media with 1% fetal bovine serum (FBS). A working concentration of DMAQB-1 that ranged from 0.5 to 500 nmol/L was studied in the presence of varying concentrations of glucose and insulin. The ability of DMAQB-1 to stimulate glucose transport at less than or equal to 100 nmol/L was determined by [(14)C]-2-deoxyglucose uptake. DNA synthesis was used as the marker for proliferative stimulus and detected by [(3)H]-thymidine uptake measured at 24 hours. Analysis of variance was used to compare the results among the groups; a P value less than.05 was considered significant. Polynomial regression was used to calculate the median lethal dose. RESULTS: In normal glucose media (100 mg/dL), various concentrations of DMAQB-1 demonstrated a small but statistically significant decrease in DNA synthesis at 0.5 nmol/L in serum-free media and at 5 nmol/L in media supplemented with 1% FBS. The corresponding median lethal dose was 107 nmol/L in serum-free media and 650 nmol/L in media supplemented with 1% FBS. A DMAQB-1 concentration of 5 nmol/L induced glucose transport that was equivalent to an insulin concentration of 100 microU/mL. In serum-free, high glucose media (200 mg/dL), DMAQB-1 concentrations up to 500 nmol/L did not cause a statistically significant change in DNA synthesis. When serum-free, high glucose media was combined with mild (100 microU/mL) or moderate (250 microU/mL) concentrations of insulin, DMAQB-1 caused no statistically significant increase in DNA synthesis. CONCLUSION: Nontoxic doses of DMAQB-1 can induce glucose transport equivalent to insulin in the physiologic range. However, DMAQB-1 does not have an insulin-like proliferative effect on human VSMCs in normal-glucose, high-glucose, or high-insulin environments.

Analysis of Variance↗
PubMed2000

Glucocorticoid receptor distribution in rat testis during postnatal development and effects of dexamethasone on immature peritubular cells in vitro.

In this study, the occurrence of the glucocorticoid receptor in the rat testis during early stages of postnatal development and its potential functional significance were investigated. Quantitative analyses of immunohistochemically labelled paraffin sections revealed that the receptor was present during all stages of postnatal development in the nuclei of interstitial cells such as Leydig cells, macrophages and fibroblasts, and endothelial cells of blood vessels. The labelling index increased initially, with maximum levels reached within the second week of postnatal development, and decreased thereafter. Within the seminiferous tubules, the glucocorticoid receptor could be detected in the nuclei of germ cells as well as Sertoli cells, reaching the highest levels in 3-week-old rats, mainly due to immature germ cell staining. In contrast, approximately 50% of the peritubular cell nuclei were stained throughout postnatal development. In vitro experiments on immature and immortalized peritubular cells demonstrated a dose-dependent and significant decrease in proliferation and fibronectin secretion after administration of dexamethasone. The data of this study suggest that glucocorticoids have a consistently repressive effect on peritubular cells throughout postnatal development. In summary, labelling of germ cells, especially in immature rats, might indicate an inhibition of spermatogenesis by corticosteroids.

Animals↗