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Biomedical subjects

J R Cook

Publications and source records attributed to J R Cook.

At least 37 records · Page 2Linked to original sources
PubMed1999

Economic impact of GPIIB/IIIA blockade after high-risk angioplasty: results from the RESTORE trial. Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis.

OBJECTIVE: This study was conducted to assess the impact of GPIIb/IIIa blockade with tirofiban on costs during the initial hospitalization and at 30 days among patients undergoing high-risk coronary angioplasty. BACKGROUND: GPIIb/IIIa blockers are a new class of compounds that have been shown in clinical studies to prevent complications after high-risk angioplasty. METHODS: The RESTORE trial was a multinational, blinded placebo-controlled study of 2,197 patients randomized to tirofiban or placebo following coronary angioplasty. This economic assessment was a prospective substudy of the RESTORE trial, and included 1,920 patients enrolled in the U.S. Costs were estimated for the U.S. cohort based on their utilization of healthcare resources and on costs measured directly in 820 U.S. patients at 30 sites. RESULTS: There was a 36% difference in the rate of the composite event of death, myocardial infarction (MI) and revascularization at two days between tirofiban and placebo (8% vs. 12%, p = 0.002). This difference was attributed to a reduction in nonfatal MI, repeat angioplasty, coronary surgery and stent placement. These clinical benefits followed a similar trend at 30 days, with a 16% reduction in the composite event (p = 0.10). In-hospital cost, including professional and study drug costs, was $12,145 +/- 5,882 with placebo versus $12,230 +/- 5,527 with tirofiban (p = 0.75). The 30-day cost was $12,402 +/- 6,147 with placebo versus $12,446 +/- 5,814 with tirofiban (p = 0.87). CONCLUSIONS: Tirofiban has been shown to decrease in-hospital and possibly 30-day events after high-risk angioplasty. The beneficial clinical effects of tirofiban in high-risk patients can be achieved at no increased cost.

Adult↗
PubMed1999

The effect of maternal exercise on fetal heart rate.

One hundred and ninety-three women with uncomplicated pregnancies and 44 with high-risk pregnancies participated in a 5-minute exercise stress test on a bicycle ergometer. All women were in the third trimester of pregnancy. Measurements of fetal heart rate were made at intervals of 2, 4, 6, 8, 10, 12, 16, 20, 25 and 30 minutes. Fetal heart rate was then compared in terms of maternal age, parity, consumption of cigarettes, exercise intensity, history of activity, cardiotocography score, maternal heart rate at rest, maternal heart rate after exercise, fetal sex and birth weight. In low-risk pregnancies an increase in fetal heart rate from 143 (124-171) beats per minute (bpm) to 148 (116-191) bpm was noted after exercise while, in the high-risk pregnancy group, a transient decrease from 148 (115-170) bpm to 141 (70-180) bpm was observed. There were also 10 cases of significant bradycardia in the high-risk pregnancy group. We conclude that the effect of maternal exercise on fetal heart rate is dependent on many variables. A fetal bradycardia following exercise is more likely to occur in high-risk pregnancies. The use of fetal heart rate variation with exercise could be a useful prognostic factor in pregnancy.

Journal Article↗
PubMed1999

Effects of adenosine on local stimulus-response latency and induction of atrial fibrillation by premature stimuli.

Premature atrial stimuli delivered during the relative refractory or "vulnerable" period exhibit increased local stimulus-response latency and may occasionally induce atrial arrhythmias. The use of adenosine to treat supraventricular tachycardias may also provoke atrial arrhythmias. In this study we investigated the effects of adenosine on the latency of premature complexes in relation to repolarization and induction of atrial arrhythmias in 14 patients without structural heart disease. A monophasic action potential catheter was used for recording in the right atrium and introducing premature stimuli (S2) at twice diastolic threshold after eight paced (S1) complexes. At short coupling intervals, S2 latency increased relative to S1 latency. S2 was delivered repeatedly at a fixed coupling interval (producing maximal local response latency) and adenosine (6 mg) was given intravenously. Adenosine decreased S2 latency significantly (23+/-5 to 11+/-3 ms, P<0.01), to values similar to S, latency. However, despite the decrease in S2 latency, the combination of adenosine and S2 more often resulted in transient atrial arrhythmias (11 of 14 patients vs 2 of 14 patients without adenosine, P<0.05). Adenosine had no effect on S, latency (9+/-2 vs. 9+/-2 ms) but decreased monophasic action potential duration from 202+/-37 to 158+/-38 ms (P<0.01). Adenosine was also given to 10 patients with S2 introduced at a coupling interval 40-50 ms less than the baseline effective refractory period. This resulted in a decrease in atrial refractoriness and capture of S2 in all cases. Latency for S2 was significantly greater than Si latency (21+/-12 vs. 9+/-2 ms, P<0.01) and transient atrial arrhythmias were induced in 9 of 10 patients. We conclude that for a given S2 coupling interval, adenosine decreases local stimulus-response latency but increases atrial vulnerability to transient atrial arrhythmias. Decreased latency may be related to a shift in the zone of relative refractoriness associated with an adenosine-mediated decrease in monophasic action potential duration. Induction of atrial arrhythmias in the presence of adenosine occurs independently of increased latency and is therefore not dependent on S2 falling within the relative refractory period at the site of stimulation.

Action Potentials↗
PubMed1999

The cost-effectiveness of losartan versus captopril in patients with symptomatic heart failure.

The Losartan Heart Failure ELITE Study recently found that in patients with symptomatic heart failure and a left ventricular ejection fraction of </=0.40, losartan compared to captopril improved survival with better tolerability. The objective of this study was to perform an economic evaluation of losartan versus captopril based on the results of the Losartan Heart Failure ELITE Study. The Losartan Heart Failure ELITE Study was a multinational, double-blind, randomized 48-week study comparing the safety and efficacy of losartan to captopril in angiotensin-converting enzyme-inhibitor-naive patients >/=65 years with symptomatic heart failure. Data on health care resource utilization were collected as part of the trial. We conducted a cost-effectiveness analysis to estimate the lifetime benefits of treatment and the associated costs. We observed no differences between treatments in the number of hospitalizations, hospital days, and emergency room visits per patient over the trial period. We estimated the total cost of losartan to be USD 54 (95% CI: USD -1,717, USD 1,755) less per patient than captopril over this time frame. We also estimated that over the projected remaining lifetime of the study population, losartan compared to captopril would increase survival by 0.20 years (undiscounted) at an average cost of USD 769 (discounted) more per patient. This cost increase translated into a cost-effectiveness ratio of USD 4,047 per year of life gained for losartan relative to captopril. In patients with symptomatic heart failure, losartan compared to captopril increased survival with better tolerability at a cost well within the range accepted as cost-effective.

Aged↗
PubMed1999

Cognitive performance in space and analogous environments.

Although human presence in space continues to expand, the literature contains relatively little coverage of human cognitive performance in the space operating environment. This article catalogs and compares the known investigations of human cognitive performance in space and in analogous environments. The methods, sample descriptions and treatments, and the results and limitations of the experiments or observations of 29 studies are compared with respect to 6 cognitive measures: (a) response time, (b) memory, (c) reasoning, (d) pattern recognition, (e) fine motor skills, and (f) dual-task performance. In general, the utility of the data is limited by small sample sizes, short observations periods, and homogeneity of the participant pool. Additionally, the variety of experimental methods used to date often makes generalization of results difficult. Although the combined results of these studies do not suggest a trend toward sustained cognitive performance impairment in the space operating environment, several cognitive performance measures do appear to be affected by an as yet undefined adaptation process.

Adaptation, Psychological↗
PubMed1999

Effect of simvastatin treatment on cardiovascular resource utilization in impaired fasting glucose and diabetes. Findings from the Scandinavian Simvastatin Survival Study.

OBJECTIVE: The Scandinavian Simvastatin Survival Study showed that simvastatin treatment reduced cardiovascular events in hypercholesterolemic subjects with coronary heart disease. The clinical benefits of therapy were similar in all three subgroups: normal fasting glucose (NFG, n = 3,237), impaired fasting glucose (IFG, n = 678), and diabetes (n = 483). This analysis compared the costs of simvastatin treatment with the costs of cardiovascular disease-related hospitalizations in the three subgroups. RESEARCH DESIGN AND METHODS: The cost of simvastatin treatment was defined as the average retail price and the cost of drug safety monitoring and adverse experiences. The costs of cardiovascular disease-related hospitalizations were determined by actual rates of hospitalization and 1995 MEDSTAT diagnosis-related group costs. RESULTS: Within trial, simvastatin treatment cost approximately $6,000 per patient. Simvastatin treatment reduced cardiovascular disease-related hospitalizations by 23% in NFG (P = 0.001), 30% in IFG (P = 0.015), and 40% in diabetic subjects (P = 0.007) within trial (median follow-up of 5.4 years). Average length of stay was reduced by 2.4 days in diabetic subjects (P = 0.021). Total cardiovascular disease-related hospital days were reduced by 28% (P < 0.001) in NFG, 38% (P = 0.005) in IFG, and 55% (P < 0.001) in diabetic subjects. For NFG subjects, simvastatin reduced the average cost of cardiovascular disease-related hospitalizations by $3,585, which offset 60% of the cost of simvastatin therapy. For IFG subjects, average cardiovascular disease-related hospitalization costs were reduced by $4,478, which offset 74% of the drug cost. For diabetic subjects, there was a net cost savings of $1,801 per subject within trial. CONCLUSIONS: Simvastatin significantly reduced cardiovascular disease-related hospitalizations and total hospital days for all three groups and significantly reduced length of stay for the diabetic group in addition to providing significant clinical benefits. The benefits were greatest in the diabetic group, with estimated cost savings within trial from simvastatin treatment.

Cardiovascular Diseases↗
PubMed1999

Differential inhibition of collagenase and interleukin-1alpha gene expression in cultured corneal fibroblasts by TGF-beta, dexamethasone, and retinoic acid.

PURPOSE: Expression of the genes for collagenase and interleukin-1alpha (IL-1alpha) are induced as stromal cells become activated to the repair fibroblast phenotype after injury to the cornea. This investigation examines the mechanisms whereby expression of these genes is inhibited by transforming growth factor-beta (TGF-beta), dexamethasone (DEX), or retinoic acid (RET A). METHODS: A model of freshly isolated cultures of corneal stromal cells and early passage cultures of corneal fibroblasts was used in these studies. This model reproduces the events of stromal cell activation in the corneal wound. RESULTS: In early passage cultures of corneal fibroblasts, expression of collagenase is under obligatory control by autocrine IL-1alpha. IL-1alpha controls its own expression through an autocrine feedback loop that is dependent on transcription factor NF-kappaB. TGF-beta, DEX, and RET A were each effective inhibitors of collagenase gene expression in these cells. Furthermore, these agents have the capacity to inhibit expression of IL-1alpha and this was correlated with their ability to affect DNA-binding activity of NF-kappaB. However, TGF-beta, DEX, and RET A were also effective inhibitors of the low level of collagenase expressed by freshly isolated corneal stromal cells that cannot express IL-1alpha. CONCLUSIONS: In cells with an active IL-1alpha autocrine loop there are at least two distinct signaling pathways by which collagenase gene expression can be modulated. The results of this study demonstrate that TGF-beta, DEX, and RET A differentially inhibit collagenase and IL-1alpha gene expression. This information will be useful in the design of therapeutic modalities for fibrotic disease in the cornea and other parts of the eye.

Animals↗
PubMed1999

Challenges in economic outcomes research.

In light of current pressures to limit health care expenditures, economic evaluations will continue to be conducted to help assess the value of new therapies or treatment programs. Although guidelines for the conduct of economic evaluations have been proposed, it is unlikely that a standard/common methodology will (or should) be used. Consequently, it is important that the reader/reviewer of such analyses be aware of the potential challenges or difficulties when evaluating these assessments. While not providing a comprehensive list of these challenges, it is hoped that this article will serve to bring awareness to some of these challenges in the design, analysis and interpretation of these evaluations.

Cost-Benefit Analysis↗
PubMed1999

Failure to activate transcription factor NF-kappaB in corneal stromal cells (keratocytes).

PURPOSE: Freshly isolated cultures of corneal stromal cells (keratocytes) are incompetent to synthesize the tissue remodeling proteinase, collagenase, in response to agents such as cytochalasin B (CB) or phorbol myristate acetate (PMA), which are strong stimulators of collagenase expression in subcultured fibroblasts of all types, including those from corneal stroma. Incompetence is due to failure to activate an autocrine interleukin (IL)1alpha feedback loop required to mediate cell response. The goal of the present study was to investigate the mechanism for this failure. METHODS: A cell culture model of freshly isolated corneal stromal cells and subcultured stromal fibroblasts from rabbits was used for these studies. RESULTS: Competence to synthesize collagenase in response to CB was acquired as a differentiation property by corneal stromal cells placed in culture, and did not require subculture. Competence acquisition correlated with transition to a fibroblastic spindle shape, assembly of actin stress fibers, and the acquired capacity to collapse in response to CB. It was demonstrated that competence could be more precisely defined as the capacity to express IL-1alpha in response to IL-1, making possible activation of the feedback loop. Investigation into the signaling pathway for IL-1alpha expression in response to IL-1 revealed a requirement for reactive oxygen species and activity of the transcription factor nuclear factor (NF)kappaB. Importantly, freshly isolated stromal cells were found to be relatively incompetent to activate NF-kappaB in comparison to subcultured stromal fibroblasts. CONCLUSIONS: Failure to activate NF-kappaB explains incompetence for expression of IL-1alpha in corneal stromal cells. Because NF-kappaB regulates many cell functions with potential to disturb corneal structure, including expression of inflammatory, stress, and degradative proteinase genes; protection against apoptosis; and cell replication; this seems likely to be an important mechanism protecting corneal stasis and preserving function.

Animals↗
PubMed1998

Presence of angiographic coronary collaterals predicts myocardial recovery after coronary bypass surgery in patients with severe left ventricular dysfunction.

BACKGROUND: Patients with coronary artery disease and left ventricular dysfunction (LVD) may have areas of hibernating myocardium that improve functionally after revascularization. Coronary collateral circulation may sustain ischemic, dysfunctional myocardium and favor myocardial recovery after revascularization. We evaluated the effect of angiographic coronary collaterals on myocardial functional recovery after coronary bypass graft (CABG) surgery in a group of patients with severe LVD. METHODS AND RESULTS: Forty-one patients with multivessel coronary artery disease and advanced LVD (left ventricular ejection fraction [LVEF] 25 +/- 5%) undergoing CABG were identified from a prospective database. Preoperative coronary angiograms were evaluated for collaterals, which were graded according to Rentrop's classification (0 to 3), and a collateral index was calculated (collateral sum divided by 3). Preoperative and postoperative radionuclide ventriculograms provided global LVEF and regional ejection fractions. Of 123 regions evaluated, 120 were dysfunctional at baseline. Virtually all (122 of 123) regions were subtended by an artery with > or = 70% stenosis that was bypassed. Thirty-eight (81%) of 47 dysfunctional regions with grade 2 or 3 collaterals improved regional ejection fraction after surgery versus 38 (52%) of 73 dysfunctional regions with grade 0 or 1 collaterals (P = 0.0018). Global LVEF was 34 +/- 10% after surgery (P < 0.001 versus before surgery). Among patients with a global LVEF increase > or = 10%, collateral index was 1.81 versus 0.83 in those with an LVEF increase < 10% (P = 0.005). CONCLUSIONS: In this population of patients with coronary artery disease with severe LVD, the presence of angiographic grade 2 or 3 collaterals predicted recovery of regional and global myocardial function after CABG.

Aged↗
PubMed1998

Influence of the preoperative signal-averaged electrocardiogram on left ventricular function after coronary artery bypass graft surgery in patients with left ventricular dysfunction. The CABG Patch Trial.

Patients with ischemic left ventricular (LV) dysfunction often have an improved survival and life quality after coronary artery bypass grafting (CABG), in part due to an improvement in LV function. A lack of LV ejection fraction (EF) improvement postoperatively portends a worse prognosis. Recently, an abnormal preoperative signal-averaged electrocardiogram (SAECG) in patients with a severely depressed LV ejection fraction undergoing elective CABG was shown to be associated with a higher early and late postoperative mortality. The present study evaluated patients with severe LV dysfunction to identify any relation between an abnormal preoperative SAECG and postoperative changes in LV function after successful CABG. Forty-five patients with LV dysfunction (LVEF <0.36) scheduled for elective CABG underwent preoperative SAECG and both pre- and postoperative LVEF determinations using radionuclide scans. Thirty-one patients in the group had an abnormal preoperative SAECG and 14 patients had a normal preoperative SAECG. Baseline patient characteristics were similar in both groups and the mean preoperative LVEF was 0.26. Overall, LVEF improved 31% postoperatively with a significantly greater benefit noted in the group with a normal baseline SAECG (14.9+/-5.7-point vs 4.8+/-8.5-point increase, p <0.001). All patients whose LVEF did not improve or worsened postoperatively had an abnormal preoperative SAECG. No SAECG measure was altered significantly by the operation. A preoperative SAECG provides information on the postoperative functional recovery of ischemic myocardium.

Aged↗
PubMed1998

Maternal-fetal tolerance is maintained despite transgene-driven trophoblast expression of MHC class I, and defects in Fas and its ligand.

During mammalian pregnancy, one or more semiallogeneic fetuses gestate in direct contact with the maternal circulation and uterine tissue. However, a damaging maternal immune response is not normally provoked. We studied two possible mechanisms for this maternal-fetal tolerance, alone and in combination. First, we directly tested the hypothesis that the striking absence of MHC class I molecules on most placenta trophoblasts protects the fetus from maternal immune attack, by creating transgenic mice which express Ld in giant cell trophoblasts. Second, because Fas ligand (FasL) may contribute to immune privilege, we tested whether functional FasL expression by the fetus, or Fas expression by the mother, contributes to successful reproduction in a fully allogeneic breeding. Our data indicate that neither abnormal expression of MHC class I in giant cells, nor disruption of the Fas-FasL system, nor a combination of these two defects, has an adverse effect on pregnancy outcome. These results suggest that during healthy allogeneic pregnancy, down-regulation of MHC class I and expression of FasL on placenta are not critical events, and other factors must prevent a harmful maternal immune response.

Adoptive Transfer↗
PubMed1998

Interactions between group homes and neighbors: neighbor preferences.

Group homes often are in conflict with their neighbors. Consequently, group home administrators tend to minimize contact between group homes and neighbors to reduce conflict. This study examined whether information about group homes and contact between homes and neighbors are related to neighbor problems as well as the preferences of potential neighbors about ways in which to become informed and involved with a group home if one were built in their neighborhood. Neighbors who interacted with residents and staff identified problems with group homes but showed fewer concerns about and had positive attitudes toward group homes generally. Potential neighbors wanted information about group homes entering their neighborhood, and preferred types of contact were associated with positive attitudes toward group homes. Group home administrators should consider neighbors as potential allies to help residents integrate into the community rather than as sources of conflict that must be avoided.

Attitude↗
PubMed1998

Proteolytic mechanisms in corneal ulceration and repair.

Corneal stromal ulceration is a devastating disorder that can cause blindness. Stromal ulceration was once thought to be a physical dissolution process, which even now is described as "melting." However, a major paradigm change occurred about 25 years ago with the demonstration of extracellular matrix-degrading activity associated with tissues isolated from ulcerating corneas. Recent studies have identified the enzymes involved as specific members of the matrix metalloproteinase (MMP) family. These studies have further provided evidence that MMPs participate at all stages of the ulcerative process, from formation of the initiating epithelial defect to ulcer resolution and repair. Roles for MMPs in these processes are discussed in this review. Studies on corneal ulceration provide basic information about failure to heal, which is useful for understanding mechanisms common to other organ systems besides the cornea.

Animals↗
PubMed1998

Peptide ligand structure influences the exchange of beta2-microglobulin by cell surface Kb.

We have studied the interactions which occur between the peptide ligand and beta2-microglobulin (beta2m) components of the class I MHC complex by analysing the process of beta2m exchange. We have previously shown that the rate of beta2m exchange on a cell-surface class I MHC complex varies with the peptide ligand to which it is bound. It remains unclear, however, whether the ability of peptide ligand to alter beta2m/heavy-chain association is related to peptide affinity, peptide structure, or both. In this article, we examine the effects of variations in peptide ligand structure on the rate of beta2m exchange by cell surface Kb complexes. Using a panel of alanine substituted variants of the MCMV peptide (YPHFMPTNL), we show that single amino acid changes in peptide sequence can have dramatic effects on the rates of beta2m exchange. The observed changes in beta2m exchange rates are directly due to modification of the peptide ligand structure as they do not reflect changes in peptide affinity. These findings suggest that peptide ligand structure can induce conformational changes in the Kb heavy chain which alter the rates of cell surface beta2m exchange, and provide further evidence for peptide-dependent fluidity of the class I heavy chain.

Alanine↗
PubMed1998

The cost and cardioprotective effects of enalapril in hypertensive patients with left ventricular dysfunction.

This study examined the effect of enalapril on survival, resource use, and cost of care in patients with left ventricular dysfunction and hypertension using a retrospective analysis of patients who participated in the Studies of Left Ventricular Dysfunction (SOLVD). Among the 6797 SOLVD participants, 1917 patients had either elevated systolic (> or = 140 mm Hg) or diastolic (> or = 90 mm Hg) blood pressure. Therapy with enalapril was associated with a significant relative risk reduction for mortality (RR = 0.819, 95% CI: 0.68 to 0.98; P = .03). This resulted in a gain of 0.11 years (95% CI: 0.00 to 0.20 years) of survival during the average 2.8 year follow-up for this subgroup and was projected to result in a gain of 2.14 years (95% CI: 0.05 to 4.21 years) during the patient's lifetime. Enalapril significantly reduced the risk of first hospitalization for heart failure by 37%. For all types of hospitalizations, there was an average reduction of 32 hospitalizations per 100 patients treated with enalapril during the trial period (95% CI: 11.8 to 52.2 hospitalizations avoided per 100 patients), resulting in an estimated net savings of $1656 per patient during the trial period (95% CI: increased cost of $191 to savings of $3502). Although the projected lifetime net savings of $1456 was not significant (95% CI: increased cost of $9243 to saving of $12,527), evaluation of the cost per life year saved indicated that enalapril represented a cost-effective strategy. The estimated clinical benefit of enalapril among the hypertensive subgroup in SOLVD supports the recommendation that angiotensin converting enzyme (ACE) inhibitors should be considered as first line pharmacologic therapy for hypertensive patients with left ventricular dysfunction. From both the clinical and economic viewpoints, ACE inhibitors provide important clinical benefits and are cost-effective.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Role of serum amyloid A as an intermediate in the IL-1 and PMA-stimulated signaling pathways regulating expression of rabbit fibroblast collagenase.

The matrix metalloproteinase collagenase is expressed by resident tissue cells only when needed for biological remodeling. Exogenous addition of inflammatory and growth-promoting cytokines stimulates collagenase expression in early passage fibroblast cultures. In addition, the signal for collagenase expression in response to phorbol-12 myristate-13 acetate (PMA) or to agents which alter cell shape in early passage fibroblast cultures is routed extracellularly to an autocrine cytokine intermediate, IL-1 alpha. Importantly, fibroblasts, when freshly isolated from the tissue, are not competent for IL-1 alpha gene expression and, therefore, cannot produce collagenase in response to shape change agents. However, they do make a small amount of collagenase in response to PMA via an IL-1-independent pathway that has not been further characterized. In this paper, we investigate the role of a second autocrine, serum amyloid A3 (SAA3), in IL-1-dependent and -independent collagenase gene expression. We demonstrate that SAA3 is required for effective stimulation of collagenase expression by either exogenous or endogenous IL-1. Furthermore, while freshly isolated fibroblasts cannot express IL-1 alpha they can express SAA3, and this autocrine mediator acts independently of IL-1 alpha to control the low level of collagenase expression that can be stimulated by PMA. These results provide further evidence for a newly emerging paradigm of collagenase regulation which emphasizes the requirement for extracellular routing of signals. They also suggest that SAA3 might be utilized independently of IL-1 alpha to control tissue remodeling in vivo.

Animals↗