Search PubMed⌕ Search

Biomedical subjects

R Segal

Publications and source records attributed to R Segal.

At least 73 records · Page 4Linked to original sources
PubMed1998

Losartan: a selective angiotensin II type 1 (AT1) receptor antagonist for the treatment of heart failure.

Losartan (COZAAR) is the prototype of a new class of potent and selective angiotensin II (AII) type 1 (AT(1)) receptor antagonists with the largest published preclinical and clinical data base. Since all of the AII antagonists are selective for the AT(1) receptor, these drugs should exhibit similar cardiovascular effects. However, since the pharmacokinetic/pharmacodynamic profiles of these agents and their degree of affinity for the AT(1) receptor differ, it is likely that differences in clinical profiles between these drugs exist and will require investigation. Losartan (parent compound), has moderate affinity for the AT(1) receptor (competitive inhibition). Losartan is well-absorbed orally as an active drug and is rapidly converted via oxidation in the human liver to a more potent metabolite (designated E3174) with an affinity 20- to 30-times greater for the AT(1) receptor (non-competitive inhibition). E3174 has a half-life of 6 - 9 h; elimination is via renal and hepatic routes. Antihypertensive and, in heart failure patients, haemodynamic activity is observed over a 24 h period with once daily dosing. Over 6 million patients have been treated for hypertension with continued excellent tolerability. Clinical experience in heart failure is growing, and recent data suggest an improved survival with losartan versus captopril, a drug from the angiotensin-converting-enzyme inhibitor class with proven benefit in this population. The current comprehensive losartan clinical end-point programme (4 large scale morbidity/mortality trials) should provide evidence regarding the efficacy of direct blockade of the AT(1) receptor with losartan compared to standard therapy: 1) The Losartan Heart Failure Survival Study - ELITE II, 2) The Losartan Post-Myocardial Infarction Survival Study - OPTIMAAL, 3) The Losartan Hypertension Survival Study - LIFE and 4) The Losartan Renal Protection Study - RENAAL.

Journal Article↗
PubMed1997

Increased growth promoting but not mast cell degranulation potential of a covalent dimer of c-Kit ligand.

The native form of soluble c-kit ligand (KL) is a noncovalent dimer. We have isolated a soluble, disulfide-linked dimer of murine KL (KL-CD) by expressing KL in Escherichia coli and refolding the denatured protein under conditions that promote the formation of both noncovalent dimers (KL-NC) and KL-CD. KL-CD exhibits a 10- to 15-fold increase in the ability to stimulate the growth of both the human megakaryocytic cell line MO7e and murine bone marrow-derived mast cells relative to KL-NC. Colony-forming assays of murine bone marrow progenitor cells also reflected this increased potency. However, KL-CD and KL-NC are equally able to prime mast cells for enhanced IgE-dependent degranulation in vitro and activate mast cells in vivo. Improving the growth-promoting activity of KL without changing its mast cell activation potential suggests that KL-CD or a related molecule could be administered in the clinic at doses that stimulate hematopoietic recovery while avoiding significant mast cell activation.

Animals↗
PubMed1997

Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE)

BACKGROUND: To determine whether specific angiotensin II receptor blockade with losartan offers safety and efficacy advantages in the treatment of heart failure over angiotensin-converting-enzyme (ACE) inhibition with captopril, the ELITE study compared losartan with captopril in older heart-failure patients. METHODS: We randomly assigned 722 ACE inhibitor naive patients (aged 65 years or more) with New York Heart Association (NYHA) class II-IV heart failure and ejection fractions of 40% or less to double-blind losartan (n = 352) titrated to 50 mg once daily or captopril (n = 370) titrated to 50 mg three times daily, for 48 weeks. The primary endpoint was the tolerability measure of a persisting increase in serum creatinine of 26.5 mumol/L or more (> or = 0.3 mg/dL) on therapy; the secondary endpoint was the composite of death and/or hospital admission for heart failure; and other efficacy measures were total mortality, admission for heart failure, NYHA class, and admission for myocardial infarction or unstable angina. FINDINGS: The frequency of persisting increases in serum creatinine was the same in both groups (10.5%). Fewer losartan patients discontinued therapy for adverse experiences (12.2% vs 20.8% for captopril, p = 0.002). No losartan-treated patients discontinued due to cough compared with 14 in the captopril group. Death and/or hospital admission for heart failure was recorded in 9.4% of the losartan and 13.2% of the captopril patients (risk reduction 32% [95% CI -4% to + 55%], p = 0.075). This risk reduction was primarily due to a decrease in all-cause mortality (4.8% vs 8.7%; risk reduction 46% [95% CI 5-69%], p = 0.035). Admissions with heart failure were the same in both groups (5.7%), as was improvement in NYHA functional class from baseline. Admission to hospital for any reason was less frequent with losartan than with captopril treatment (22.2% vs 29.7%). INTERPRETATION: In this study of elderly heart-failure patients, treatment with losartan was associated with an unexpected lower mortality than that found with captopril. Although there was no difference in renal dysfunction, losartan was generally better tolerated than captopril and fewer patients discontinued losartan therapy. A further trial, evaluating the effects of losartan and captopril on mortality and morbidity in a larger number of patients with heart failure, is in progress.

Aged↗
PubMed1997

Kinetics of cytokine production in experimental systemic lupus erythematosus: involvement of T helper cell 1/T helper cell 2-type cytokines in disease.

We followed cytokine production from induction through disease progression in a murine model of experimental systemic lupus erythematosus (SLE). SLE was induced by immunization with the human monoclonal anti-DNA Ab that bears the common Id designated 16/6 Id. BALB/c and C3H.SW mice that are susceptible to SLE induction and C57BL/6 mice that are resistant were immunized with the 16/6 Id. Cytokine production was tested periodically for 7 mo. Increased production of IL-2 and IFN-gamma, the Th1-type cytokines, was detected in BALB/c and C3H.SW mice 2 to 4 mo following immunization. IL-4 and IL-10, the Th2-type cytokines predominated later in disease course, and peaked 5 mo following disease induction. At this stage the Th1 type cytokines dropped to levels below those observed in controls. IL-4 production also dropped rapidly to very low levels, while IL-10 production decreased but remained above control levels. The ratio of IgG2a/IgG1 of DNA and 16/6 Id-specific Abs peaked at 2 mo following disease induction and decreased later, in concordance with the higher production of Th2-type cytokines. Thus, the development of experimental SLE in mice involves two stages: increased production of Th1-type, followed by increased induction of Th2-type cytokines. High levels of the proinflammatory cytokines, TNF-alpha and IL-1, were maintained throughout disease course. No significant changes were detected in the cytokine profile of C57BL/6 immunocytes following immunization with the 16/6 Id, supporting the possible role of the cytokine network in SLE.

Animals↗
PubMed1997

Toxicity profile of dual methotrexate combinations with gold, hydroxychloroquine, sulphasalazine and minocycline in rheumatoid arthritis patients.

The purpose of the present study was to evaluate the toxicity and tolerability of methotrexate (MTX)/gold (G; group 1) combination therapy as compared to other MTX combinations [MTX with hydroxychloroquine (HCQ; group 2), MTX with sulphasalazine (SASP; group 3) and MTX with minocycline (MNC; group 4)]. The hospital records of 127 consecutive rheumatoid arthritis (RA) patients who were treated with these combinations during a period of 24 months were retrospectively reviewed. The toxicity and tolerability of the MTX/G combination was compared to the other dual MTX combinations and also to MTX alone using data previously reported by us on 126 RA patients treated with single MTX therapy. The mean exposure time to treatment was 16 months in group 1 and 13 months in the other dual MTX combinations. During the period of follow-up, the combination was stopped in 22 out of 42 patients in group 1 (52%) in comparison with 54 patients out of 86 patients (63%) in the other dual regimen groups. The discontinuation rate was highest in group 4 (due to side effects and lack of compliance) and this was statistically significant in comparison with group 1. The proportion of adverse events was lowest in group 1 (14%) and highest in groups 3 and 4 (25%). Side effects were reversible and comparable with those of MTX alone (23%). No fatal or life-threatening side effects were recorded during any of these MTX combination therapies. We concluded that the combinations of MTX with G, HCQ, SASP and MNC in RA were relatively well tolerated. No increase in toxicity compared with MTX alone was observed. The lowest rate of side effects was noted in group 1, while group 4 presented the highest discontinuation rate.

Adult↗
PubMed1997

Effect of aging on cytokine production in normal and experimental systemic lupus erythematosus afflicted mice.

The objective of the this study was to determine the cytokine profile of aging mice and to establish whether changes in cytokine production account for the fact that aging mice develop a milder disease than the young in response to induced experimental systemic lupus erythematosus (SLE). Cytokine secretion was evaluated in groups of BALB/c and C3H.SW mice at different ages between 2 and 24 months. The production of IL-2, IL-4, IL-10, IFN gamma and TNF alpha was determined in supernatants of ConA-stimulated splenocytes and that of IL-1 in the supernatants of LPS-stimulated peritoneal macrophages. A gradual age-related decline was observed in the production of IL-2 and IFN gamma, whereas the levels of IL-4, IL-10, IL-1 and TNF alpha progressively increased with aging, in unimmunized BALB/c and C3H.SW mice. Experimental SLE was induced in 2 and 10 month old C3H.SW mice by immunization with the monoclonal anti-DNA antibody bearing the 16/6 Id. The characteristic cytokine profile following immunization of 2 month old mice was early increased production of TNF alpha and IL-1, followed by a peak of Th1 type cytokines (IL-2, IFN gamma). At a later stage of the disease, a peak of Th2 type cytokines (IL-4, IL-10) was observed that was concomitant with low levels of Th1 cytokines. In contrast, in the 10 month old mice that were immunized with 16/6 Id only a mild increase in all the above cytokines was observed. We suggest that the lower autoantibody production and moderate clinical manifestations in aging mice with experimental SLE are causally related to the decreased production of pro-inflammatory cytokines at the initial stages of the disease followed by a lower production of both Th1 and Th2 type cytokines.

Aging↗
PubMed1997

The Pharmacists' Implementation of Pharmaceutical Care (PIPC) model.

PURPOSE: Study purpose was to develop a theoretical framework that will explain pharmacists' behavior relative to the provision of pharmaceutical care. The model was developed from four attitude models by testing their predictive validity relative to pharmaceutical care implementation. Four hypotheses and one research question were investigated to identify determinants of behavioral intention and behavior. METHODS: 617 community pharmacists in the state of Florida, U.S.A., were surveyed twice using mail survey methodology to collect data. The first survey assessed community pharmacists' attitude, subjective norm, perceived behavioral control, past behavior recency, self-efficacies, instrumental beliefs and affect. The second survey assessed pharmacists' behavior relative to the implementation of pharmaceutical care. After establishing reliability and validity of measures, regression analysis was used to test hypotheses and research question investigated. RESULTS: The Pharmacists' Implementation of Pharmaceutical Care (PIPC) model developed postulates that (i) behavior is directly determined by past behavior recency, behavioral intention and perceived behavioral control; (ii) psychological appraisal processes-instrumental beliefs, self-efficacies, and affect toward means-influence behavior through past behavior recency; and (iii) behavioral intention is determined by attitude, social norm and perceived behavioral control. CONCLUSIONS: The PIPC model provides a formal scientifically validated theoretical framework which can be used to design successful intervention for pharmaceutical care implementation.

Community Pharmacy Services↗
PubMed1997

Applying the principles of pharmaceutical care to the patient with diabetes.

Current medical care for patients with diabetes neither meets the guidelines from the American Diabetes Association (ADA) nor approaches the levels of intensive care in the Diabetes Control and Complications Trial (DCCT). The drug-use process for patients with diabetes could be enhanced by improving the way in which drug therapy is monitored and managed. The concept of pharmaceutical care strategically redefines the drug-use process into a pharmaceutical care system in which the pharmacist takes responsibility for monitoring the effects of drugs and acts to resolve drug-related problems before they become a drug-related morbidity. A method for implementing a pharmaceutical care service using practice guidelines to help a pharmacist provide consistent care to all patients with diabetes is discussed.

Cost of Illness↗
PubMed1997

Cytokine manipulation by methotrexate treatment in murine experimental systemic lupus erythematosus.

OBJECTIVE: We reported beneficial effects of methotrexate (MTX) treatment on clinical variables in the murine model of experimental systemic lupus erythematosus (SLE). We now follow the kinetics of several cytokines that are involved in experimental SLE, to find out whether MTX treatment has an effect on cytokine production. METHODS: SLE was induced in naive BALB/c female mice by injection of the human monoclonal anti-DNA antibody bearing the common idiotype, 16/6 Id. Six weeks after booster injection, when high levels of autoantibodies were observed, MTX treatment was started (2 mg/kg once a week) for 7 months. Cytokine production by macrophages or splenocytes from these mice was determined monthly by either ELISA or bioassays. RESULTS: A significant increase in the production of tumor necrosis factor-alpha was determined as early as 2 weeks after injection. Interleukin 1 (IL-1) production increased gradually, starting one month after disease induction. These proinflammatory cytokines reached very high levels that were maintained through disease course. MTX treatment reduced production of these cytokines to normal levels throughout the experimental period. Increased levels of IL-2 and interferon-gamma (IFN-gamma), the Th1 type cytokines, were detected 2-4 months after disease induction. The secretion of the latter then dropped to levels lower than those observed in control mice. Treatment with MTX reversed levels of the cytokines to levels observed in healthy mice, IL-4 and IL-10, the Th2 type cytokines, predominated later in disease course, 5 months after immunization. Two to 3 months later production of IL-4 dropped to levels lower than those of control mice. IL-10 secretion remained higher than in controls throughout the experiment. The production of both IL-4 and IL-10 in MTX treated mice was also similar to that of control mice. CONCLUSION: The restoration of the cytokine profile to normal levels observed in the MTX treated mice from the initial steps of disease induction suggests its beneficial effects in SLE might be mediated through modulation of cytokine production.

Animals↗
PubMed1997

The development and evaluation of the hypertension temporal orientation (HTO) scale.

Temporal orientation is a multidimensional concept that describes the perception of time among individuals. Time perception is structured by life experiences and can vary depending upon the particular context involved. Whether a person is past-, present- or future-oriented has been shown to influence his/her approach and reaction to health situations. Because the management of hypertension is based on achieving some future health state, hypertension provides a context in which an individual's time perspective may be particularly influential. One purpose of this study was to develop and evaluate a scale to measure temporal orientation that was specific to hypertension, namely the hypertension temporal orientation (HTO) scale. Data were collected via telephone interviews with 300 people who had been diagnosed by a physician as having hypertension. Principal components factor analysis revealed three dimensions of hypertension temporal orientation: (1) a nonexperiential domain; (2) an experiential disease domain; and (3) an experiential treatment domain with coefficient alpha estimates of 0.76, 0.66, and 0.63, respectively. The HTO scale was significantly discriminant of African Americans and whites on the experiential treatment domain whereby African Americans were more present-oriented regarding the daily management (or treatment) of hypertension as compared to whites. Additional evidence for the validity of the HTO scale was found with temporal orientation group comparisons on health perceptions. The findings provide early support for the reliability and validity of the HTO scale for measuring temporal orientation among people with hypertension.

Adult↗
PubMed1996

Behavioral pharmaceutical care scale for measuring pharmacists' activities.

The development and validation of a behavioral pharmaceutical care scale (BPCS) is described. The BPCS items were constructed by conducting an extensive review of the literature on pharmaceutical care and a focus group meeting. To validate the instrument, data were collected from 617 community pharmacists in Florida. Reliability coefficients for the BPCS domains were > 0.70, and the content validity index value for the whole instrument was 0.79. Evidence supporting trait validity of the BPCS was provided by using confirmatory factor analysis to confirm the instrument's dimensionality. Nomologic validity was established by confirming the hypothesis that pharmacists who in a prior survey reported they intend to provide pharmaceutical care would have a significantly higher BPCS score than those who reported they do not intend to provide pharmaceutical care. The behavioral pharmaceutical care scale, developed as a tool for measuring pharmacists' efforts to provide pharmaceutical care, was found to be reliable, sensitive, and valid.

Adult↗
PubMed1996

Regulation and organization of the groE and dnaK operons in Eubacteria.

groEL and dnaK are the most highly conserved protein-coding genes known. Most groEL operons and several dnaK and dnaJ operons contain a highly conserved inverted repeat (IR) sequence in their regulatory region. So far, this IR has been found only as part of the groE, dnaK and dnaJ operons and genes. In most cases, the IR is part of the operon transcript, and is involved in the regulation of expression at both the DNA and mRNA levels. A detailed analysis of groE and dnaK operons indicates that the organization of the groE operons is highly conserved. They contain only the groES and groEL genes and always in the same order. In contrast, the organization of the dnaK operons has changed during evolution: genes have been added and deleted from it, and the gene order within the operon is variable.

Amino Acid Sequence↗
PubMed1996

The effects of health and treatment perceptions on the use of prescribed medication and home remedies among African American and white American hypertensives.

This study examines the relationships between health beliefs and the use of both prescribed medication and home remedies among a group of African American and White American hypertensives. Data were collected via telephone interviews with 300 individuals who had been medically diagnosed as having hypertension and had been prescribed at least one antihypertensive medication. Using the health belief model (HBM) as the theoretical framework, 4 primary hypotheses involving the perceptions of severity, susceptibility, benefits and costs of each treatment and compliance with prescribed mediation (Rx) and use of home remedies (HR) were tested. Multivariate logistic regression analyses indicated that age, costs of Rx and benefits of HR predicted compliance with Rx. The primary predictors of use of HR were ethnicity, poverty status, education, severity, benefits and costs of HR. The differences in predictor variables for each treatment behavior are discussed and speculations about the nature and importance of these differences are offered. Study findings support the suggestion that patient beliefs about their disease and their evaluations of treatment options should be considered when developing therapeutic plans and when monitoring patient outcomes.

Black or African American↗
PubMed1996

Treatment of Candida nail infection with terbinafine.

BACKGROUND: Terbinafine is a highly potent drug against dermatophytes. Data regarding its effectiveness against Candida species are few and variable. OBJECTIVE: Our purpose was to evaluate the efficacy and safety of oral terbinafine in patients with Candida nail infection. METHODS: In an open-label uncontrolled study, 20 patients completed 16 weeks of treatment with terbinafine, 250 mg/day, and an additional 8 weeks with placebo. Efficacy was assessed clinically and mycologically at weeks 0 (baseline), 4, 8, 16, 24, 36, and 48. Routine laboratory studies were performed at baseline and weeks 4, 8, and 16. RESULTS: At the end of the trial 60% of target nails were cured clinically and mycologically; in 10% there was mycologic cure with residual clinical signs, in 25% a moderate improvement (> 50%), and failure in only 5% (one patient). Most nails were infected by Candida parapsilosis. Two of 28 patients showed mild reversible elevation of liver enzymes 1 month after initiation of terbinafine treatment. CONCLUSION: The administration of terbinafine for 16 weeks is effective in the treatment of Candida nail infection. Liver enzyme values should be determined during the first month of treatment.

Administration, Oral↗
PubMed1996

Treatment of chronic unstable angina pectoris: use of a totally implantable programmable device for continuous intrathecal infusion of opiates: case report.

We report the case of a 70-year-old man with a 17-year history of angina pectoris, who had previously suffered two documented myocardial infarctions and undergone multiple diagnostic cardiac catheterizations, two coronary artery bypass operations, and several percutaneous transluminal coronary angioplasty procedures. The patient had experienced unstable angina for the past 3 years refractory to maximal medical therapy and was unsuitable for further attempts at revascularization. After a successful trial of epidural infusion of morphine, a totally implantable programmable continuous-infusion device with an intrathecal catheter was implanted in the patient on August 18, 1993, resulting in maintained pain resolution. His gardening, carpentry, and other activities of daily living were limited only by shortness of breath. Six months later, the pump treatment did not mask the development of a myocardial infarction. To the best of our knowledge, this is the first report of the use of continuous intrathecal infusion of morphine or the use of a totally implantable programmable infusion device for angina pectoris. We propose that in carefully selected patients with chronic unstable angina, continuous intrathecal infusion of morphine may relieve effort-induced pain without resulting in myocardial infarction.

Aged↗