Biomedical subjects

S E Kimmel

Publications and source records attributed to S E Kimmel.

At least 19 recordsLinked to original sources

PubMed2006

A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) is characterised by in situ thrombosis and increased thromboxane (Tx) A2 synthesis; however, there are no studies of antiplatelet therapy in IPAH. The aim of the current study was to determine the biochemical effects of aspirin (ASA) and clopidogrel on platelet function and eicosanoid metabolism in patients with IPAH. A randomised, double-blind, placebo-controlled crossover study of ASA 81 mg once daily and clopidogrel 75 mg once daily was performed. Plasma P-selectin levels and aggregometry were measured after exposure to adenosine diphosphate, arachidonic acid and collagen. Serum levels of TxB2 and urinary metabolites of TxA2 and prostaglandin I2 (Tx-M and PGI-M, respectively) were assessed. A total of 19 IPAH patients were enrolled, of whom nine were being treated with continuous intravenous epoprostenol. ASA and clopidogrel significantly reduced platelet aggregation to arachidonic acid and adenosine diphosphate, respectively. ASA significantly decreased serum TxB2, urinary Tx-M levels and the Tx-M/PGI-M ratio, whereas clopidogrel had no effect on eicosanoid levels. Neither drug significantly lowered plasma P-selectin levels. Epoprostenol use did not affect the results. In conclusion, aspirin and clopidogrel inhibited platelet aggregation, and aspirin reduced thromboxane metabolite production without affecting prostaglandin I2 metabolite synthesis. Further clinical trials of aspirin in patients with idiopathic pulmonary arterial hypertension should be performed.

Adult↗

PubMed2001

Secondary hypoparathyroidism attributed to hypomagnesemia in a dog with protein-losing enteropathy.

Severe hypomagnesemia (0.8 mg/dl; reference range, 1.6 to 2.3 mg/dl), hypocalcemia, and protein-losing enteropathy were identified in a 5-year-old castrated male 3-kg (6.6 lb) Shih Tzu examined because of anorexia, lethargy, paresis, and abdominal distention. Histologic examination of intestinal biopsy specimens revealed lymphangiectasia and lymphocytic, plasmacytic, neutrophilic infiltrates. Initial treatment included administration of magnesium (0.80 mEq/kg [0.36 mEq/lb]) of body weight in a balanced electrolyte solution. This treatment resulted in normalization of the serum magnesium concentration (1.7 mg/dl); resolution of the lethargy, paresis, and tachycardia; and an increase in the serum parathyroid hormone and ionized calcium concentrations. Findings were consistent with secondary hypoparathyroidism attributable to hypomagnesemia. Magnesium concentration should be monitored in all dogs with gastrointestinal tract disease, especially those with protein-losing enteropathy, anorexia, and weakness.

Animals↗

PubMed2001

Selective serotonin reuptake inhibitors and myocardial infarction.

BACKGROUND: Depression is an independent risk factor for myocardial infarction (MI). Selective serotonin reuptake inhibitors (SSRIs) may reduce this risk through attenuation of serotonin-mediated platelet activation in addition to treatment of depression itself. METHODS AND RESULTS: case-control study of first MI in smokers 30 to 65 years of age was conducted among all 68 hospitals in an 8-county area during a 28-month period. Cases were patients hospitalized with a first MI. Approximately 4 community control subjects per case were randomly selected from the same geographic area using random digit dialing. Detailed information regarding use of antidepressant medication as well as other clinical and demographic data were obtained by telephone interview. A total of 653 cases of first MI and 2990 control subjects participated. After adjustment, using multivariable logistic regression, for age, sex, race, education, exercise, quantity smoked per day, body mass index, aspirin use, family history of MI, number of physician encounters, and history of coronary disease, diabetes, hypertension, or hypercholesterolemia, the odds ratio for MI among current SSRI users compared with nonusers was 0.35 (95% CI 0.18, 0.68; P<0.01). Non-SSRI antidepressant users had a nonsignificant reduction in MI risk with wide confidence intervals (adjusted odds ratio 0.48, CI 0.17, 1.32; P=0.15). However, analysis of this group was limited by the small number of exposed subjects. CONCLUSIONS: The use of SSRIs may confer a protective effect against MI. This could be attributable to the inhibitory effect SSRIs have on serotonin-mediated platelet activation or possibly amelioration of other factors associated with increased risk for MI in depression.

Adult↗

PubMed2001

Incidence and prognostic value of low plasma ionized calcium concentration in cats with acute pancreatitis: 46 cases (1996-1998).

OBJECTIVE: To determine the incidence and prognostic significance of low plasma ionized calcium concentration in cats with clinical signs of acute pancreatitis (AP). DESIGN: Retrospective study. ANIMALS: 46 cats with AP and 92 control cats with nonpancreatic diseases. PROCEDURE: Medical records were reviewed, and results of clinicopathologic testing, including plasma ionized and total calcium concentrations, acid-base values, and electrolyte concentrations, were recorded. Cats with AP were grouped on the basis of outcome (survived vs died or were euthanatized), and plasma ionized calcium concentrations, acid-base values, and electrolyte concentrations were compared between groups. RESULTS: Serum total calcium concentration was low in 19 (41%) cats with AP, and plasma ionized calcium concentration was low in 28 (61%). Cats with AP had a significantly lower median plasma ionized calcium concentration (1.07 mmol/L) than did control cats (1.12 mmol/L). Nineteen (41%) cats with AP died or were euthanatized; these cats had a significantly lower median plasma ionized calcium concentration (1.00 mmol/L) than did cats that survived (1.12 mmol/L). Ten of the 13 cats with AP that had plasma ionized calcium concentrations < or = 1.00 mmol/L died or were euthanatized. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that low plasma ionized calcium concentration is common in cats with AP and is associated with a poorer outcome. A grave prognosis and aggressive medical treatment are warranted for cats with AP that have a plasma ionized calcium concentration < or = 1.00 mmol/L.

Acid-Base Equilibrium↗

PubMed2001

Adjustments for center in multicenter studies: an overview.

Increasingly, investigators rely on multicenter or multigroup studies to demonstrate effectiveness and generalizability. Authors too often overlook the analytic challenges in these study designs: the correlation of outcomes and exposures among patients within centers, confounding of associations by center, and effect modification of treatment or exposure across center. Correlation or clustering, resulting from the similarity of outcomes among patients within a center, requires an adjustment to confidence intervals and P values, especially in observational studies and in randomized multicenter studies in which treatment is allocated by center rather than by individual patient. Multicenter designs also warrant testing and adjustment for the potential bias of confounding by center, and for the presence of effect modification or interaction by center. This paper uses examples from the recent biomedical literature to highlight the issues and analytic options.

Bias↗

PubMed2001

Epidemiologic review of the calcium channel blocker drugs. An up-to-date perspective on the proposed hazards.

In the setting of soaring popularity, postmarketing studies of calcium channel blockers came to suggest an increase in a variety of major adverse end points. The evidence, however, was largely observational, and large-scale trials capable of addressing the concerns were wanting. Clinical trials now support the safety and efficacy of the long-acting dihydropyridines for patients with both uncomplicated and diabetic hypertension, although conventional therapies and, in the latter case, angiotensin-converting enzyme inhibitors have superior proof of benefit. By contrast, short-acting dihydropyridines should be avoided. In the acute coronary syndromes, beta-blockers remain the treatment of choice; the evidence for nondihydropyridines remains inconclusive. Stable angina calls for beta-blockers as first-line therapy and nondihydropyridines as second-line therapy, whereas in ventricular dysfunction, safety data for nondihydropyridines are lacking. Initial reports of cancer, bleeding, and suicide have been contradicted by subsequent data, making the associations uncertain or unlikely. Remaining questions await completion of ongoing trials to better define the indications for these agents.

Bias↗

PubMed2001

Current research on rapid cycling bipolar disorder and its treatment.

Rapid cycling is a pattern of presentation of bipolar disorder that specifies the course of the illness and is associated with a greater morbidity. The validity of rapid cycling as a distinct course modifier for bipolar disorder has been demonstrated and the term has been incorporated into the DSM-IV. The phenomenon of rapid cycling tends to appear late in the course of the disorder, occurs more frequently among females, and is more frequently seen in patients with bipolar type II disorder. Stimulants such as cocaine may also play some role in rapid-cycling. It is generally accepted that a recent history of rapid cycling predicts non-response to monotherapy with lithium and probably carbamazepine as well; however it is also possible that concurrent use of antidepressants may play a role in destabilizing the illness course under these agents. Thus, clinical considerations suggest that discontinuing antidepressants may facilitate the recovery process. Among clinically available monotherapies, valproate and lamotrigine appear to be the most useful clinically. However, other treatments such as lithium, carbamazepine, the atypical antipsychotic agents, thyroid hormone, and bupropion are frequently needed augmentation strategies. Electroconvulsive therapy may also prove efficacious in selected cases. The present paper provides a critical review of the evidence for the foregoing clinical issues in rapid cycling.

Acute Disease↗

PubMed2001

The effects of contemporary use of coronary stents on in-hospital mortality. Registry Committee of the Society for Cardiac Angiography and Interventions.

OBJECTIVES: This study was designed to determine the effect of coronary stents on in-hospital mortality. BACKGROUND: Despite extensive use of stents for percutaneous coronary interventions (PCIs), their effect on serious in-hospital events, especially mortality, is not well defined. METHODS: A cohort study was performed using 16,811 consecutive native-vessel PCI procedures performed on patients in the Society for Cardiac Angiography & Interventions Registry from July 1, 1996, through December 31, 1998. Patients undergoing balloon-only angioplasty were compared with those receiving a planned or unplanned stent. Procedures with other devices were excluded. Multivariable analyses adjusted for detailed clinical characteristics and for individual laboratory. RESULTS: Stents were associated with a significant reduction in in-hospital mortality (0.3%) compared with balloon procedures (0.6%; multivariable odds ratio [OR] 0.55; 95% confidence interval [CI] 0.34, 0.89; p = 0.014). The risk of emergency coronary bypass also was reduced by stenting (0.3% vs. 0.7%; multivariable OR 0.47; 95% CI: 0.29, 0.76; p = 0.002). Adjustment for the use of glycoprotein IIb/IIIa inhibitors did not change the results, and the effects of stenting relative to balloon procedures were similar in those procedures with and without glycoprotein IIb/IIIa blockade (p = 0.94). CONCLUSIONS: This study suggests that coronary stenting, compared with balloon procedures, reduces in-hospital mortality, independent of the clinical setting.

Adult↗

PubMed2001

Risk of acute first myocardial infarction and use of nicotine patches in a general population.

OBJECTIVES: To determine if nicotine patches, both as prescribed and used over-the-counter, increase the risk of first myocardial infarction (MI). BACKGROUND: Although nicotine patches improve smoking cessation rates, case reports have raised the hypothesis that they may increase the risk of MI. METHODS: A population-based case-control study among 68 hospitals in an eight-county region surrounding Philadelphia was performed to determine if nicotine patches increase the risk of first MI. Cases were smokers (current or within the prior year) admitted to all hospitals in the region with a first MI. Controls were smokers (current or within the prior year) without prior MI selected from the same region using random-digit dialing. Data were collected by telephone interviews and chart reviews. The study had 80% power to detect an odds ratio (OR) of 2.5. RESULTS: A total of 653 cases and 2,990 controls were interviewed. There was no association between nicotine patches and MI (OR 0.46; 95% CI: 0.09, 1.47), and the confidence interval (CI) excluded an effect from nicotine patches equal to that from cigarette smoking itself (OR < 2.5). Among those who abstained from smoking, the OR for use of nicotine patches was 0.25 (95% CI: 0.01, 1.67); among those who smoked concomitantly, the OR for patch use was 0.83 (95% CI: 0.09, 3.81). Adjustment for confounding did not alter the study's findings (OR adjusted for confounders that could mask a harmful effect of patches: 0.70; 95% CI: 0.20, 2.46). CONCLUSIONS: Nicotine patches, as used in actual practice, do not appear to be associated with an increased risk of MI.

Administration, Cutaneous↗

PubMed2001

Perioperative beta-blocker withdrawal and mortality in vascular surgical patients.

OBJECTIVE: Our purpose was to determine the effect of postoperative beta-blocker withdrawal on mortality and cardiovascular events after vascular surgery. METHODS: Detailed data were collected on perioperative cardiovascular medication use and discontinuation and cardiovascular risk factors among consecutive major vascular surgical procedures at two university hospitals. RESULTS: A total of 140 patients received beta-blockers preoperatively. Mortality in the 8 patients who had beta-blockers discontinued postoperatively (50%) was significantly greater than in 132 patients who had beta-blockers continued (1.5%, odds ratio 65.0, P<.001). The effect of beta-blocker discontinuation was unaffected by adjustment by stratification for risk factors (all P< or =.01), for contraindications to restarting beta-blockers (P = .006), and by multivariable analyses adjusting for potential confounders (adjusted odds ratio 17.0, P =.01). beta-Blocker discontinuation also was associated with increased cardiovascular mortality (0% vs 29%, P =.005) and postoperative myocardial infarction (odds ratio 17.7, P =.003). CONCLUSION: Discontinuing beta-blockers immediately after vascular surgery may increase the risk of postoperative cardiovascular morbidity and mortality.

Adrenergic beta-Antagonists↗

PubMed2001

Evolving methodologies in bipolar disorder maintenance research.

Background During the development of a new treatment for bipolar disorder, maintenance studies are used to evaluate the ability of the putative mood stabiliser to prevent relapse and recurrence of further episodes. Comparisons with the early bipolar disorder maintenance studies indicate that the methodologies of recent trials have evolved substantially. Aims To review the methods used in the first- and second-generation maintenance studies, highlighting the differences of the various designs. Method Literature review. Results Methods that have evolved the most include patient enrolment, randomisation schemes and the use of outcome measures and statistical analyses. In addition, regulatory and commercial issues have also influenced study design. Conclusion There is little consensus on the methodology of bipolar disorder maintenance studies. As the integration of newer therapies into routine clinical practice is dependent on the evidence from controlled studies, it is essential that future maintenance trials in bipolar disorder achieve adequate methodological rigour without sacrificing overall feasibility.

Journal Article↗

PubMed2001

Evolving methodologies in bipolar disorder maintenance research.

BACKGROUND: During the development of a new treatment for bipolar disorder, maintenance studies are used to evaluate the ability of the putative mood stabilizer to prevent relapse and recurrence of further episodes. Comparisons with the early bipolar disorder maintenance studies indicate that the methodologies of recent trials have evolved substantially. AIMS: To review the methods used in the first- and second-generation maintenance studies, highlighting the differences of the various designs. METHOD: Literature review. RESULTS: Methods that have evolved the most include patient enrollment, randomisation schemes and the use of outcome measures and statistical analyses. In addition, regulatory and commercial issues have also influenced study design. CONCLUSION: There is little consensus on the methodology of bipolar disorder maintenance studies. As the integration of newer therapies into routine clinical practice is dependent on the evidence from controlled studies, it is essential that future maintenance trials in bipolar disorder achieve adequate methodological rigour without sacrificing overall feasibility.

Antimanic Agents↗

PubMed2001

Bipolar rapid cycling: focus on depression as its hallmark.

The phenomenon of frequent cycling in bipolar disorder was first recognized by Emil Kraepelin in 1913. More recently, rapid cycling has been reported to be a predictor of nonresponse to treatment. At the time of presentation, most patients with DSM-IV-defined rapid cycling appear to be in the depressed phase of their illness. Frequent and more severe episodes of depression appear to be the hallmark of rapid cycling. Reported in this article are recent preliminary data suggesting that the combination of lithium and divalproex sodium administered continuously over 6 months appears to result in marked acute and continuation antimanic efficacy in 85% of patients and marked antidepressant efficacy in 60%. However, only one half of patients experienced bimodal stabilization. Comorbid alcohol, cannabis, and/or cocaine abuse and/or dependence did not appear to directly affect the spectrum of efficacy of lithium and divalproex or response rates in compliant patients. Comorbidity appeared to alter prognosis by increasing the prevalence of poor compliance. The majority of patients receiving lithium and divalproex who required additional treatment were depressed, suggesting that the frequent recurrence of depression is the primary unmet need in patients with rapid cycling. The use of antidepressants in this population has been discouraged because of concerns about the possibility of cycle acceleration. There exists a need for a pharmacotherapy that not only possesses marked acute antidepressant properties, but that does so without inducing switching or cycle acceleration. A double-blind, placebo-controlled trial of lamotrigine monotherapy in bipolar I depression has demonstrated efficacy without causing switching at a rate exceeding placebo; however, this initial study excluded patients with rapid cycling. To explore the efficacy of lamotrigine in rapid cycling, a recent multicenter study has examined lamotrigine as a maintenance therapy for this population. The results indicate that lamotrigine may be a useful treatment for patients with rapid-cycling bipolar II disorder and that this drug has begun to address this unmet need.

Anticonvulsants↗

PubMed2000

Effects of coronary stents on cardiovascular outcomes in broad-based clinical practice.

BACKGROUND: Although stents have been shown to reduce the need for repeated percutaneous coronary intervention (PCI) in randomized trials, the effects of stents in broad-based, diverse clinical practice have not been well studied, nor has their effect on subsequent myocardial infarction or cardiac death. METHODS: A retrospective cohort study was performed that included all 43 hospitals performing PCI in Pennsylvania in the last quarter of 1995, with the use of the Pennsylvania Health Care Cost Containment Council database. All 5258 patients who underwent PCI, excluding those with previous PCI within the preceding 6 months, were included. The primary outcomes were in-hospital events (death or coronary bypass), 6-month revascularization rates, and 6-month rates of cardiac death or myocardial infarction. RESULTS: A total of 1240 patients (24%) had a stent procedure. Compared with nonstent procedures, stents reduced the risk of in-hospital events (multivariable odds ratio adjusted for patient and hospital level differences, 0.63; 95% confidence interval, 0.41-0.97), primarily because of a 52% reduction in the need for coronary bypass. Stents also reduced the need for follow-up revascularization procedures (multivariable hazard ratio, 0.72; 95% confidence interval, 0.59-0. 87), primarily because of a 31% reduction in repeated PCI. However, stents had no effect on 6-month rate of myocardial infarction or cardiac death (multivariable hazard ratio, 0.97; 95% confidence interval, 0.71-1.33). CONCLUSIONS: Using stents decreases the need for repeated PCI in broad-based clinical practice, confirming results from randomized trials. However, this study did not detect any effect on subsequent myocardial infarction or cardiac death.

Adult↗

PubMed2000

Hypomagnesemia and hypocalcemia associated with protein-losing enteropathy in Yorkshire terriers: five cases (1992-1998).

OBJECTIVE: To determine clinical and laboratory findings associated with protein-losing enteropathy, hypomagnesemia, and hypocalcemia in Yorkshire Terriers. DESIGN: Retrospective study. ANIMALS: 5 purebred or crossbred Yorkshire Terriers with protein-losing enteropathy, hypomagnesemia, and hypocalcemia. PROCEDURE: Medical records were reviewed for dogs with protein-losing enteropathy, hypomagnesemia, and hypocalcemia. RESULTS: Of 8 dogs with these signs, 5 had Yorkshire Terrier breeding. Common findings were diarrhea, abdominal effusion, leukocytosis, neutrophilia, hypocalcemia (ionized calcium), hypomagnesemia, hypoproteinemia, hypoalbuminemia, hypocholesterolemia, and increased serum activity of aspartate aminotransferase. CONCLUSIONS AND CLINICAL RELEVANCE: Yorkshire Terriers are at increased risk for development of protein-losing enteropathy with hypomagnesemia and decreased ionized calcium concentration. Hypomagnesemia and hypocalcemia may have a related pathogenesis involving intestinal loss, malabsorption, and abnormalities of vitamin D and parathyroid hormone metabolism. Serum electrolyte replacement may be required to avoid neurologic and metabolic problems.

Animals↗

PubMed2000

Sex and myocardial infarction: an epidemiologic perspective.

The relation between sexual activity and acute myocardial infarction (MI) risk is one of great interest to people at risk for MI and their physicians. However, understanding this relation requires an appreciation of the complex interplay among relative, attributable, and absolute risk. Because there is an underlying risk of MI in the population, the risk of MI after sexual activity must be compared with this underlying baseline risk. The estimated relative risk of MI after sexual activity is approximately 2.5 during the 2-hour period after sex, indicating a 2.5-fold increase in risk over baseline. However, because the baseline risk during any 2-hour period is very low, the absolute increase in risk (the risk from sexual activity minus the baseline risk), is extremely small (e.g., 0.01% over a year for low-risk individuals engaging in weekly sexual activity and 0.1% for higher-risk individuals). In addition, the attributable risk (the percentage of MIs due to sexual activity) is <1%. Thus, any individual's risk of MI during sexual activity is low. Nonetheless, factors that may decrease the risk of MI after sexual activity are important to explore, and include regular exercise and perhaps medication use, such as aspirin and beta blockers. Although there may be a long-term cardiovascular and mortality benefit to regular sexual activity, current data supporting this theory are limited. This article describes the relation between sexual activity and acute MI with respect to the complex interplay among relative, attributable, and absolute risk. Limitations of studies examining the potential long-term benefits of regular sexual activity are also discussed.

Adult↗

PubMed2000

Management of sexual dysfunction in patients with cardiovascular disease: recommendations of the Princeton Consensus Panel.

Sexual dysfunction is highly prevalent in both sexes and adversely affects patients' quality of life and well being. Given the frequent association between sexual dysfunction and cardiovascular disease, in addition to the potential cardiac risk of sexual activity itself, a consensus panel was convened to develop recommendations for clinical management of sexual dysfunction in patients with cardiovascular disease. Based upon a review of the research and presentations by invited experts, a classification system was developed for stratification of patients into high, low, and intermediate categories of cardiac risk. The large majority of patients are in the low-risk category, which includes patients with (1) controlled hypertension; (2) mild, stable angina; (3) successful coronary revascularization; (4) a history of uncomplicated myocardial infarction (MI); (5) mild valvular disease; and (6) no symptoms and <3 cardiovascular risk factors. These patients can be safely encouraged to initiate or resume sexual activity or to receive treatment for sexual dysfunction. An important exception is the use of sildenafil in patients taking nitrates in any form. Patients in the intermediate-risk category include those with (1) moderate angina; (2) a recent MI (<6 weeks); (3) left ventricular dysfunction and/or class II congestive heart failure; (4) nonsustained low-risk arrhythmias; and (5) >/=3 risk factors for coronary artery disease. These patients should receive further cardiologic evaluation before restratification into the low- or high-risk category. Finally, patients in the high-risk category include those with (1) unstable or refractory angina; (2) uncontrolled hypertension; (3) congestive heart failure (class III or IV); (4) very recent MI (<2 weeks); (5) high-risk arrhythmias; (6) obstructive cardiomyopathies; and (7) moderate-to-severe valvular disease. These patients should be stabilized by specific treatment for their cardiac condition before resuming sexual activity or being treated for sexual dysfunction. A simple algorithm is provided for guiding physicians in the management of sexual dysfunction in patients with varying degrees of cardiac risk.

Adult↗

PubMed2000

Management of sexual dysfunction in patients with cardiovascular disease: recommendations of The Princeton Consensus Panel.

Humans↗