Initial experience with the low-molecular-weight heparin, enoxaparin, in combination with the platelet glycoprotein IIb/IIIa blocker, tirofiban, in patients with non-ST segment elevation acute coronary syndromes.

Enoxaparin, a low-molecular-weight heparin, and tirofiban, an intravenous platelet glycoprotein IIb/IIIa receptor antagonist, have each been shown to be effective in reducing cardiac ischemic events compared to unfractionated heparin alone in separate trials of patients with unstable angina and non-Q wave myocardial infarction. The combination of these agents may offer further therapeutic benefit. In a pilot study (ACUTE I), fifty-five patients with non-Q wave myocardial infarction were randomized to receive double-blind treatment with tirofiban (0.

AKT induces transcriptional activity of PU.1 through phosphorylation-mediated modifications within its transactivation domain.

Signal transduction by the antigen receptor complexes is critical for developmental progression of B-lymphocytes, which are defined by assembly and sequential expression of immunoglobulin genes, which in turn are regulated by the enhancer elements. Although proximal antigen-receptor signal transduction pathways are well defined, the precise nuclear factors targeted by these signals remained unknown. Previous studies have demonstrated that tissue-restricted transcription factors including PU.

Postmenopausal osteoporosis: fracture consequences and treatment efficacy vary by skeletal site.

At least half of all postmenopausal women will experience fractures during their lifetime, and the consequences are often serious, but most women at risk are not receiving adequate treatment. The objective of this paper is to summarize the literature concerning the consequences of osteoporotic fractures, and the effectiveness of pharmacologic agents for preventing fractures and their consequences, emphasizing a systematic, evidence-based summary of treatment results from randomized, controlled trials that were published previously. Osteoporosis is associated with increased risk of fractures at most skeletal sites.

Investigation of alternating and continuous experimental task designs during single finger opposition fMRI: a comparative study.

The purpose of this study was to empirically investigate and compare the effects of alternating and continuous experimental task designs on blood oxygenation level dependent (BOLD) signal contrast. Six healthy volunteers underwent single-finger opposition functional magnetic resonance imaging (fMRI) using T2*-weighted echo planar imaging technique on a 1.5 T MR scanner.

Blood group associations with parasites, bacteria, and viruses.

Although recent investigations into the human blood groups have proceeded mainly at the molecular level, the RBC remains an exquisite model to study the expression of various genes and their related proteins. Although DNA may be informative, it may not always give meaningful information regarding protein expression on cell surfaces, which is where binding occurs. Because of their easy accessibility, RBCs will continue to be used as a major tool in the investigation of the causative agents for disease, whether they be viral, bacterial, or parasitic in nature.

Impact of enoxaparin low molecular weight heparin in patients with Q-wave myocardial infarction.

A subgroup meta-analysis from the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) and the Thrombolysis in Myocardial Infarction (TIMI) 11B studies has shown that enoxaparin is superior to unfractionated heparin in reducing the composite end points of death, myocardial infarction, and emergency revascularization in patients with Q-wave myocardial infarction. The beneficial treatment effect was significant at 43 days.

Age-related changes in interferon-alpha/beta receptor expression, binding, and induction of apoptosis in natural killer cells from C57BL/6 mice.

Natural killer (NK) cells are a critical first line of defense against viral infections and tumors. We showed previously that basal NK cytotoxicity was comparable in adult (6 month) and aged (24 month) C57BL/6 (B6) mice. However, NK activity was significantly higher in adult compared with aged B6 mice after either in vitro or in vivo stimulation with IFN-alpha/beta.

[Membrane biophysical interaction of amlodipine and antioxidant properties].

Objective: To assess the potential benefits of the antioxidant activity of certain pharmacological agents that may be beneficial in the treatment of cardiovascular disease, including coronary heart disease and heart failure, by reducing irreversible cell injury due to oxyradical damage.

Methods: The antioxidant activities of representative calcium antagonists were examined and correlated with the molecular membrane interactions of the compounds, as measured by radioligand binding assays and high resolution differential scanning calorimetry.

Results: The results of these experiments show a direct relationship between the antioxidant activities of the calcium antagonists and their affinity for the membrane lipid bilayer, as well as their ability to modulate membrane thermodynamic properties (amlodipine > verapamil >> diltiazem).

The depression in primary care tool kit.

Objective: A tool kit was developed to help primary care physicians overcome some of the barriers to recognition and management of depression.

Method: Tools were collected from a variety of sources, categorized by function, and evaluated on the basis of previously established criteria, with the best tools selected for inclusion in the tool kit. New tools were developed when an adequate tool for a desired function was not available.

Apoptosis and cardiomyopathy.

Apoptosis is a form of cell death that has been described as distinct from necrotic cell death. It is believed to be genetically programmed and occurs as a physiologic process in various organ systems of body. Although it has been tacitly believed that apoptosis does not occur in the terminally differentiated adult heart muscle cells, studies in endomyocardial biopsies from patients with dilated and ischemic cardiomyopathy and in explanted hearts from patients with end-stage heart failure undergoing cardiac transplantation have demonstrated histochemical evidence of apoptosis.

A community-based assessment of heat-related morbidity in North Philadelphia.

A 6-month community-based study designed to (1) determine the perceptions and barriers affecting the overall quality of life of isolated older adults greater than 65 years of age, (2) assess their risk factors, health attitudes, and beliefs concerning their susceptibility to heat-related conditions, and (3) evaluate the effectiveness of an age-specific innovative intervention program consisting of a specially marked clock-like thermometer and other creative educational materials was conducted among 34 participants during the spring and summer of 1997 in north Philadelphia. The study objectives were measured at preintervention (baseline) and at 8 weeks postintervention follow-up using a 24-item pretest/posttest self-administered questionnaire. We report the short-term benefit of our intervention, theorize that innovative strategies targeting at-risk older adults should be culturally sensitive and age-specifically appropriate, and recommend that more vigorous research methods should be implemented to lend credence to our findings.

Antioxidant activity of the monoamine oxidase B inhibitor lazabemide.

Free radical-induced damage to lipid and protein constituents of neuronal membranes contributes to the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD). The development of an effective inhibitor of oxidative stress represents an important goal for the treatment of AD. In this study, the intrinsic antioxidant activity of lazabemide, a potent and reversible inhibitor of monoamine oxidase B (MAO-B), was tested in a membrane-based model of oxidative stress.

Predictors of treatment outcome in sexually abused children.

Problem: This study evaluated the impact of child and family characteristics on treatment outcome of sexually abused children.

Method: Forty-nine recently sexually abused 7- to 14-year-old children were randomly assigned to either abuse-focused cognitive behavioral therapy or nondirective supportive therapy, and assessed pre- and post-treatment using several standardized instruments. These included five measures of psychological symptomatology and four measures of child and family characteristics hypothesized to mediate treatment response.

Predictors of recurrent ischemic events and death in unstable coronary artery disease after treatment with combination antithrombotic therapy.

Background: Patients with non-Q-wave acute coronary syndromes (ACS) have substantial rates of recurrent ischemic events, but prognostic studies have been small or preceded the routine use of aggressive combination antithrombotic therapy. We sought to identify predictors of these events after antithrombotic treatment of non-Q-wave ACS.

Methods: We assessed 30-day rates of a composite triple end point (death, infarction, or refractory angina) and double end point (death or infarction) among 3171 patients with non-ST-segment elevation ACS randomly assigned to enoxaparin or heparin, plus aspirin, for 2 to 8 days.

Coronary vascular responses to short-term cocaine administration in conscious baboons compared with dogs.

Objectives: Cardiovascular complications of cocaine use represent an important clinical problem, yet the mechanisms by which cocaine predisposes to myocardial ischemia are poorly understood.

Background: The effects of cocaine on the coronary circulation have been studied extensively in experimental animal models, but have failed to recapitulate the clinical findings reported in humans who use cocaine.

Methods: We studied 12 conscious, chronically instrumented dogs and 5 conscious, chronically instrumented baboons to determine whether there were important species differences in the response to cocaine.

Barriers and solutions to implementing a new curriculum: lessons from the women's health education program at MCP Hahnemann School of Medicine.

The integration of new knowledge into the medical school curriculum is a difficult process. This article proposes effective strategies for overcoming obstacles to curricular integration of women's health and sex and gender topics. Some techniques developed to overcome barriers to the integration of new material into an existing curriculum include faculty development, faculty rewards, development of competencies and assessment tools, interdisciplinary team teaching, standardized patients, and reference resources.

Functional localization of a "Time Keeper" function separate from attentional resources and task strategy.

The functional neuroanatomy of time estimation has not been well-documented. This research investigated the fMRI measured brain response to an explicit, prospective time interval production (TIP) task. The study tested for the presence of brain activity reflecting a primary time keeper function, distinct from the brain systems involved either in conscious strategies to monitor time or attentional resource and other cognitive processes to accomplish the task.

Genetic differences in the age-associated decrease in inducibility of natural killer cells by interferon-alpha/beta.

Natural killer (NK) cells, which are important in viral infections and anti-tumor activity, show reduced cytotoxicity in aged mice. The mechanism(s) for this age-related decline in NK activity has not been clearly established. We assessed changes in NK cytotoxicity in splenocytes and peripheral blood mononuclear cells after interferon (IFN)-alpha/beta stimulation in adult (6 months) and aged (22-26 months) C57Bl/6, Balb/c, and (Balb/c x C57Bl/6)F1 mice.

Hypothalamo-pituitary-adrenal cortical responses to low-dose physostigmine and arginine vasopressin administration: sex differences between major depressives and matched control subjects.

Of heuristic value in understanding the neurochemistry of major depression is whether the hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity that occurs in this illness can be related to putative neurotransmitter dysfunction(s). Cholinergic neurotransmission stimulates hypothalamic corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) secretion, both of which stimulate pituitary corticotropin (ACTH) secretion, but whether the HPA axis in humans is activated only by doses of cholinergic agonists that produce noxious side effects remains controversial. To test the hypothesis of increased cholinergic sensitivity in major depression, physostigmine (PHYSO), a reversible cholinesterase inhibitor, was administered to patients and control subjects at a dose that elevated plasma ACTH, cortisol, and AVP concentrations but produced few or no side effects.

Truncus arteriosus and other lethal internal anomalies in Goltz syndrome.

An infant girl of 36 weeks gestational age was found to have cardiovascular and other lethal internal anomalies in addition to characteristic external abnormalities of focal dermal hypoplasia (Goltz syndrome). The internal anomalies included truncus arteriosus type II with truncal origin of hypoplastic pulmonary arteries, cardiac ventricular septal defect, severe hypoplasia of lungs and pulmonary veins, massive diaphragmatic hernia, and absence of the right kidney. Such a combination of severe anomalies has not been reported previously in Goltz syndrome.

Association of Pur alpha and E2F-1 suppresses transcriptional activity of E2F-1.

Protein-protein interaction can play an important role in the control of several biological events including gene transcription, replication and cell proliferation. E2F-1 is a DNA-binding transcription factor which, upon interaction with its target DNA sequence, induces expression of several S phase specific genes allowing progression of the cell cycle. Evidently, the activity of this protein is modulated by its cellular partner, pRb, which in the hypophosphorylated form, binds to E2F-1 and inactivates its transcriptional ability.

Calcium channel blockers, apoptosis and cancer: is there a biologic relationship?

Calcium channel blockers (CCBs) represent a chemically and pharmacologically diverse group of agents that are widely used for the treatment of hypertension and angina. A small number of retrospective, observational analyses have raised concern about a potential causal link between CCB use and an increased risk for cancer development. Despite the absence of cancer findings in extensive preclinical studies, it has been proposed that CCBs may work differently in humans by interfering with apoptosis, leading to an increased potential for abnormal cell proliferation and tumor growth.

The effect of benchmarking clinical practice with the clinical laboratory. An institutional case study.

The improvement of quality in clinical care can greatly benefit form continuous benchmarking with information based on laboratory data. To be most effective, the information is best provided in the form of real-time disease management decision support. Such an approach requires advances in the implementation of hospital information systems.