Biomedical subjects

J E Soberman

Publications and source records attributed to J E Soberman.

6 recordsLinked to original sources

PubMed2004

Obesity, leptin resistance, and the effects of insulin reduction.

Leptin resistance is a hallmark of obesity, but its etiology is unknown, and its clinical measurement is elusive. Leptin-sensitive subjects have normal resting energy expenditure (REE) at a low leptin concentration, while leptin-resistant subjects have a normal REE at a higher leptin concentration; thus, the ratio of REE:Leptin may provide a surrogate index of leptin sensitivity. We examined changes in REE and leptin in a cohort of 17 obese subjects during experimental weight loss therapy with the insulin-suppressive agent octreotide-LAR, 40 mg i.m. q28d for 6 months. Six subjects lost significant weight (>10%) and BMI (>-3 kg/m(2)) with a 34% decline in leptin and a 46% decrease in insulin area under the curve (IAUC) to oral glucose tolerance testing. These subjects maintained their pretreatment REE, and thus exhibited a rise in REE:Leptin, while the other 11 showed minimal changes in each of these parameters. For the entire cohort, the change in IAUC correlated negatively with the change in REE:Leptin. These results suggest that the REE:Leptin ratio, while derivative, may serve as a useful clinical indicator of changes in leptin sensitivity within obese subjects. They also support the possibilities that hyperinsulinemia may be a proximate cause of leptin resistance, and that reduction of insulinemia may promote weight loss by improving leptin sensitivity.

Adult↗

PubMed2000

Spironolactone in congestive heart failure.

When a large multicenter research trial is abruptly terminated, it is usually a consequence of significant adverse events. In contrast, when the Randomized Aldactone Evaluation Study (RALES) mortality trial was discontinued 18 months early, it was because of the prominent salutary effect of spironolactone, added to standard multidrug therapy consisting of an angiotensin converting enzyme (ACE) inhibitor and loop diuretic (with or without digoxin), in reducing the incidence of death and hospitalization in patients with severe congestive heart failure (CHF). Therapies directed toward suppression of neurohormonal activation have contributed to significant reductions in morbidity and mortality. ACE inhibitors, in particular, have had the largest impact on adverse outcome measures in CHF. Yet despite combined therapy with an ACE inhibitor and loop diuretic, patients on these agents still have an unacceptably high incidence of progressive ventricular failure and death. In the years that followed its discovery in 1954, aldosterone was considered a target for therapy in CHF because of its role in sodium retention. It is now clear that chronic elevations in plasma aldosterone are responsible for many other adverse effects (Fig. 1), including enhanced potassium and magnesium excretion, myocardial fibrosis, inhibition of catecholamine reuptake, endothelial cell and baroreceptor dysfunction, and ventricular arrhythmias. Blockade of aldosterone action is a desirable pharmacologic approach to treating both the underlying pathophysiology of CHF and its clinical consequences. Spironolactone promotes magnesium and potassium retention, increases uptake of myocardial norepinephrine, attenuates formation of myocardial fibrosis, and decreases mortality associated with both progressive ventricular dysfunction and malignant ventricular arrhythmias. Despite the encouraging results seen in the recent RALES mortality trial, a diagnosis of CHF still carries 30% to 40% mortality at 2 years. We need to continue the trend of evaluating newer therapies directed at the pathophysiologic mechanisms of this syndrome, with a goal toward delaying and eventually reversing long-term consequences.

Aldosterone↗

PubMed2000

Effect of disease states on theophylline serum concentrations: are we still vigilant?

The use of theophylline has decreased over the past decade because of concerns over the risks of serious adverse effects as well as availability of more effective, safer drugs. Because of this decline in use, some clinicians may not be alert to the marked effect of some disease states on theophylline serum concentrations. The purpose of this review is to heighten awareness of the effect of decompensated heart failure, cor pulmonale, hepatic dysfunction, thyroid disease, and febrile illness on theophylline serum concentrations. Because many patients receive some benefit from this drug, safe use by clinicians requires closer monitoring of serum concentrations in patients with factors that alter theophylline clearance, including several disease states.

Cystic Fibrosis↗

PubMed1999

Beta-blockers after myocardial infarction: do benefits ever outweigh risks in asthma?

beta-Blockers are well documented to prolong life in patients after myocardial infarction (MI), yet patients who also have asthma are frequently and understandably denied this therapy. We reviewed the literature (via MEDLINE) for the past 35 years for beta-blocker-induced asthma, and reexamined potential beta-blocker use in the context of NIH guidelines for asthma classification and management. Because beta-blockers can cause fatal or life-threatening asthma, their use should be avoided in moderate to severe persistent asthmatics. Benefits of low-dose beta(1)-blockers (e.g. atenolol 50 mg daily) may outweigh risks in some patients with mild intermittent or well-controlled mild persistent asthma. Further study is needed to verify that low doses of beta(1)-blockers are effective in prolonging life after MI, and that use specifically in mild intermittent or mild persistent asthma per NIH classification is safe.

Adrenergic beta-1 Receptor Antagonists↗

PubMed1989

Clinical performance and therapeutic potential of celiprolol in angina pectoris.

Celiprolol, a long-acting, beta 1-selective adrenergic blocking drug, with peripheral beta 2-stimulatory and peripheral alpha 2-inhibitory action, has a unique pharmacologic profile. Its antianginal properties have been evaluated in comparison with those of propranolol and atenolol. Efficacy was assessed by improvement in time to exercise-limiting angina and to onset of ST-segment depression, as well as by symptomatic improvement. Celiprolol has been demonstrated to have antianginal and anti-ischemic effects comparable with both propranolol and atenolol, with a decreased incidence of bradycardia noted in the celiprolol-treated cohorts. No significant adverse effects or laboratory abnormalities were noted in these cohorts. Current indications for beta-blocker therapy are numerous. Cardioprotective effects and reduction in ischemic potential have been identified in a variety of clinical settings. Decreased morbidity and mortality in the postinfarct period have been well documented. Effects on supraventricular and ventricular arrhythmias, in the presence or absence of ischemia, are well known. Favorable hemodynamic effects in the peri- and postoperative period of coronary artery bypass surgery are described. More recently, beta-blocker therapy that is effective against angina has also been demonstrated effective in the reduction of silent ischemia. The different hemodynamic properties of the newer beta-blockers may provide additional therapeutic effects in many clinical situations.

Adrenergic beta-Antagonists↗

PubMed1988

Celiprolol in angina pectoris.

Celiprolol, a long-acting beta1-selective adrenergic-blocking drug with peripheral beta2-stimulatory and peripheral a2-inhibitory activities, has a unique vasodilator beta-blocker pharmacologic profile. The efficacy and safety of celiprolol in angina pectoris have been demonstrated in multiple studies that highlight its different hemodynamic properties compared with traditional beta-blockers. Celiprolol was found to be an effective antianginal agent compared with placebo. In addition, in angina and ischemia its efficacy was comparable to that of propranolol and atenolol.

Adrenergic beta-Antagonists↗