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J Crouse

Publications and source records attributed to J Crouse.

9 recordsLinked to original sources
PubMed1999

Rationale and design of the Arterial Disease Multiple Intervention Trial (ADMIT) pilot study.

The primary objectives of the pilot study were to: (1) evaluate the feasibility of recruiting patients with peripheral arterial disease (PAD); (2) measure the efficacy and safety of high-density lipoprotein (HDL)-raising treatment, low-density lipoprotein (LDL)-lowering therapy, antioxidant therapy, antithrombotic therapy, and their combinations; and (3) assess adherence to a complex multiple drug regimen. Secondary objectives included measurement of the effect of the interventions on prespecified biochemical markers, maintenance of therapy masking (in particular with niacin), and measurement of the intervention's impact on functional status and on quality of life. To date, no secondary prevention trial has been conducted specifically among patients with PAD. Intermittent claudication affects about 0.5% to 1.0% of persons aged >35 years. There is a striking increase in incidence of PAD with age, particularly among those aged >50 years in both sexes, although men are twice as likely as women to develop PAD. The Arterial Disease Multiple Intervention Trial was a double-blind randomized pilot trial of 468 participants with documented PAD. A 2 x 2 x 2 factorial design was used to evaluate the effect of 3 interventions. The pilot incorporated several major novel design features: first, the use of a simple noninvasive method (measurement of ankle brachial index) to identify a population with either symptomatic or asymptomatic PAD; and second, a lipid modifying strategy to increase HDL with nicotinic acid in the intervention group while lowering LDL levels equally with an hydroxymethylglutaryl-coenzyme A reductase inhibitor as needed in the intervention and control group. Two other arms, the antioxidant arm (consisting of beta-carotene and vitamins E and C) and the antithrombotic arm (using warfarin) were also added. Adherence to therapy was measured by pill count, and success in treatment was measured by the proportion of values in target range for HDL, LDL, and the international normalized ratio.

Adult↗
PubMed1998

Erythropoietin receptor and STAT5-specific pathways promote SKT6 cell hemoglobinization.

Erythrocyte production in mammals is known to depend on the exposure of committed progenitor cells to the glycoprotein hormone erythropoietin (Epo). In chimeric mice, gene disruption experiments have demonstrated a critical role for Epo signaling in development beyond the erythroid colony-forming unit (CFU-e) stage. However, whether this might include the possible Epo-specific induction of red blood cell differentiation events is largely unresolved. To address this issue, mechanisms of induced globin expression in Epo-responsive SKT6 cells have been investigated. Chimeric receptors containing an epidermal growth factor (EGF) receptor extracellular domain and varied Epo receptor cytoplasmic domains first were expressed stably at physiological levels in SKT6 cells, and their activities in mediating induced hemoglobinization were assayed. While activity was exerted by a full-length chimera (EE483), truncation to remove 7 of 8 carboxyl-terminal tyrosine sites (EE372) markedly enhanced differentiation signaling. Moreover, mutation of a STAT5 binding site in this construct (EE372-Y343F) inhibited induced globin expression and SKT6 cell hemoglobinization, as did the ectopic expression of dominant-negative forms of STAT5 in parental SKT6 cells. As in normal CFU-e, SKT6 cells also were shown to express functional receptors for stem cell factor (SCF). To further define possible specific requirements for differentiation signaling, effects of SCF on SKT6 cell hemoglobinization were tested. Interestingly, SCF not only failed to promote globin expression but inhibited this Epo-induced event in a dose-dependent, STAT5-independent fashion. Thus, effects of Epo on globin expression may depend specifically on STAT5-dependent events, and SCF normally may function to attenuate terminal differentiation while promoting CFU-e expansion.

Animals↗
PubMed1997

Hematopoietic cell phosphatase negatively regulates erythropoietin-induced hemoglobinization in erythroleukemic SKT6 cells.

In an increasing number of hematopoietic cytokine receptor systems (T-cell receptor, B-cell receptor, and macrophage colony-stimulating factor, stem cell factor, interleukin-3, and erythropoietin [EPO] receptors), inhibitory roles for the protein tyrosine phosphatase hematopoietic cell phosphatase (HCP; SHPTP1, PTP1C, and SHP1) have been defined in proliferative signaling. However, evidence exists to suggest that HCP also may exert important effects on blood cell differentiation. To investigate possible roles for HCP during late erythroid differentiation, effects of manipulating HCP expression or recruitment on EPO-induced hemoglobinization in erythroleukemic SKT6 cells have been investigated. No effects of EPO on levels of HCP, Syp, Stat5, the EPO receptor, or GATA-1 expression were observed during induced differentiation. However, the tyrosine phosphorylation of JAK2, the EPO receptor, and Stat5 was efficiently activated, and HCP was observed to associate constitutively with the EPO receptor in this differentiation-specific system. In studies of HCP function, inhibition of HCP expression by antisense oligonucleotides enhanced hemoglobinization, whereas the enforced ectopic expression of wild-type (wt) HCP markedly inhibited EPO-induced globin expression and Stat5 activation. Based on these findings, epidermal growth factor (EGF) receptor/EPO receptor chimeras containing either the wt EPO receptor cytoplasmic domain (EECA) or a derived HCP binding site mutant (EECA-Y429,431F) were expressed in SKT6 cells, and their abilities to mediate differentiation were assayed. Each chimera supported EGF-induced hemoglobinization, but efficiencies for EECA-Y429,431F were enhanced 400% to 500%. Thus, these studies show a novel role for HCP as a negative regulator of EPO-induced erythroid differentiation. In normal erythroid progenitor cells, HCP may act to prevent premature commitment to terminal differentiation. In erythroleukemic SKT6 cells, this action also may enforce mitogenesis.

Animals↗
PubMed1996

Cost-effectiveness of pravastatin in secondary prevention of coronary artery disease.

This study analyzed the cost-effectiveness of pravastatin in secondary prevention of coronary artery disease (CAD). The projected risk model in 445 male patients with established CAD and moderately elevated serum low-density lipoprotein cholesterol used results data from 2 placebo-controlled plaque regression trials: Pravastatin Limitation of Atherosclerosis in the Coronary Arteries and Pravastatin, Lipids, and Atherosclerosis in the Carotids. Framingham Heart Study data were used to project the risk of mortality 10 years after myocardial infarction (MI) for incremental male patients in the placebo group who had MI. A Markov process was used to estimate life-years saved, and decision analysis was used to estimate cost. Depending on the patient-risk profile, the midrange estimated cost per life-year saved with pravastatin in secondary prevention of CAD varied from $7,124 to $12,665, which is favorable compared with other widely accepted medical interventions.

Anticholesteremic Agents↗
PubMed1994

Comparison of the effects of exercise in water and on land on the rehabilitation of patients with intra-articular anterior cruciate ligament reconstructions.

BACKGROUND AND PURPOSE: Exercises in water have been shown to be effective for improving strength and passive range of motion (PROM). Traditional rehabilitation following intra-articular anterior cruciate ligament (ACL) reconstruction has taken place on land. This study was designed to compare the effects of exercises in water on strength and girth of the thigh musculature, knee PROM, joint laxity, effusion, and functional outcome with the effects of similar exercises on land in subjects following intra-articular reconstruction of the ACL. SUBJECTS: Twenty subjects were randomly assigned to either a group that exercised on land or a group that exercised in water. METHODS: Thigh girth, joint effusion, and knee PROM measurements were recorded at 2-week intervals for the first 8 weeks postoperatively. Isokinetic and isometric peak torque measurements for the thigh musculature, knee joint laxity assessments, and Lysholm scores were obtained at the end of 8 weeks. RESULTS: Higher outcome scores were recorded in the water group than in the land group, as measured by Lysholm scales. No differences were noted between groups for knee PROM, thigh girth, or quadriceps femoris muscle performance. In the water group, less joint effusion was noted after the 8 weeks. In the land group, greater peak torque for isokinetic knee flexion was recorded. CONCLUSION AND DISCUSSION: Although exercise in water may not be as effective as exercise on land for regaining maximum muscle performance, rehabilitation in water may minimize the amount of joint effusion and lead to greater self-reports of functional improvement in subjects with intra-articular ACL reconstructions.

Activities of Daily Living↗
PubMed1987

Measurement of the temporal and spatial parameters of gait using a microcomputer based system.

This paper describes a system for measuring the temporal and spatial parameters of gait. The basis of the system is a resistive grid walkway which is controlled by a microcomputer which also collects, processes and stores the data from the walkway. The data obtained from the system, including the temporal and spatial parameters of gait such as step and stride lengths, the durations of swing and support phases of the gait cycle and walking speed, are presented in both numerical and graphical forms. Accuracy to within 1 cm has been verified by analysing videotapes of foot placement during a walk. Special emphasis has been placed on making the system software user-friendly. The presentation of date uses several types of display, from a simple graphical summary of the walk statistics to a more complete report showing all the data from each stride. In the year during which the walkway system has been operational, it has been found easy to use by both subjects and operators, and it produces very useful data.

Biomedical Engineering↗
PubMed1983

HLA and disease: haplotype sharing in multiplex families.

Recently it has been argued that the distribution of shared haplotypes in multiplex sibships for HLA-associated diseases may be an indicator of the disorder's underlying mode of transmission. Specifically, it has been suggested that the presence of multiple disease susceptibility genes and/or loci may be inferred when an inverse relationship between the amount of haplotype sharing and the number of affected sibs is observed in families where neither parent is affected. This claim is evaluated using extensive computer simulations. It is shown that a variety of haplotype sharing patterns are possible, even for the simplest models, and that for a large segment of the parameter space the actual distribution of shared haplotypes is opposite to that predicted. Accordingly, the inference that more than one locus is involved in the etiology of an HLA-associated non-Mendelian disease, if based only on the distribution of shared haplotypes in multiplex sibships, is unjustified.

Genetic Diseases, Inborn↗
PubMed1983

HLA sharing in multiplex sibships.

For an arbitrary number of affected sibs with unaffected parents, the proportion that share both marker haplotypes identical by descent is derived for the generalized single locus model. This proportion is shown to depend on the underlying parameters of the disease transmission model, on the total sibship size and on the number of sibs who are affected. The variety of identity by descent patterns suggests that any attempt to infer the presence of other independent disease susceptibility loci solely on the basis of an observed inverse relationship between the degree of haplotype sharing and the number of affected sibs, is liable to result in spurious conclusions.

Chromosome Mapping↗