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Biomedical subjects

J A Ferguson

Publications and source records attributed to J A Ferguson.

At least 19 recordsLinked to original sources

Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure.

PURPOSE: Because the bioavailability of oral furosemide is erratic and often incomplete, we tested the hypothesis that patients with heart failure who were treated with torsemide, a predictably absorbed diuretic, would have more favorable clinical outcomes than would those treated with furosemide. PATIENTS AND METHODS: We conducted an open-label trial of 234 patients with chronic heart failure (mean [+/- SD] age, 64 +/- 11 years) from an urban public health care system. Patients received oral torsemide (n = 113) or furosemide (n = 121) for 1 year. The primary endpoint was readmission to the hospital for heart failure. Secondary endpoints included readmission for all cardiovascular causes and for all causes, numbers of hospital days, and health-related quality of life. RESULTS: Compared with furosemide-treated patients, torsemide-treated patients were less likely to need readmission for heart failure (39 [32%] vs. 19 [17%], P <0.01) or for all cardiovascular causes (71 [59%] vs. 50 [44%], P = 0.03). There was no difference in the rate of admissions for all causes (92 [76%] vs. 80 [71%], P = 0.36). Patients treated with torsemide had significantly fewer hospital days for heart failure (106 vs. 296 days, P = 0.02). Improvements in dyspnea and fatigue scores from baseline were greater among patients treated with torsemide, but the differences were statistically significant only for fatigue scores at months 2, 8, and 12. CONCLUSIONS: Compared with furosemide-treated patients, torsemide-treated patients were less likely to be readmitted for heart failure and for all cardiovascular causes, and were less fatigued. If our results are confirmed by blinded trials, torsemide may be the preferred loop diuretic for patients with chronic heart failure.

Aged↗

A fiber-optic lactate sensor based on bacterial cytoplasmic membranes.

A new type of fiber-optic biosensor based on bacterial cytoplasmic membranes (CPM) as the biological recognition element and an oxygen sensitive dye layer as the transducer is described for the detection of lactate. CPMs from bacteria with an induced lactate oxidase system are adsorbed onto a cellulose disk. The disk is fixed mechanically over an oxygen sensitive siloxane layer on the distal end of an optical fiber. This system detects lactate with no interference from glucose, fructose or glutamic acid.

Bacteria↗

High-density fiber-optic DNA random microsphere array.

A high-density fiber-optic DNA microarray sensor was developed to monitor multiple DNA sequences in parallel. Microarrays were prepared by randomly distributing DNA probe-functionalized 3.1-microm-diameter microspheres in an array of wells etched in a 500-microm-diameter optical imaging fiber. Registration of the microspheres was performed using an optical encoding scheme and a custom-built imaging system. Hybridization was visualized using fluorescent-labeled DNA targets with a detection limit of 10 fM. Hybridization times of seconds are required for nanomolar target concentrations, and analysis is performed in minutes.

Base Sequence↗

Incidence of stroke and season of the year: evidence of an association.

Evidence of seasonal variation in the incidence of stroke is inconsistent. This may be a likely consequence of one or more methodological shortcomings of the studies investigating this issue, including inappropriate analytic models, insufficient length of time, small sample size, and a regional (vs. national) focus. The authors' objective was to ascertain whether an association exists between season of the year and the incidence of stroke by using a methodological approach designed to overcome these limitations. The authors used a longitudinal study design involving 72,779 veterans hospitalized for stroke at any Veterans Affairs hospital nationally during the years 1986-1995. These data were analyzed by using time series methods. There was clear evidence of a seasonal occurrence for stroke in general. This seasonal effect was found for ischemic stroke, but not for hemorrhagic stroke. The peak occurrence was in mid-May. Neither the region (i.e., climate) nor the race of the patient substantially modified the seasonal trend. An explanation for this pattern remains to be determined.

Adult↗

Screening unlabeled DNA targets with randomly ordered fiber-optic gene arrays.

We have developed a randomly ordered fiber-optic gene array for rapid, parallel detection of unlabeled DNA targets with surface immobilized molecular beacons (MB) that undergo a conformational change accompanied by a fluorescence change in the presence of a complementary DNA target. Microarrays are prepared by randomly distributing MB-functionalized 3-microm diameter microspheres in an array of wells etched in a 500-microm diameter optical imaging fiber. Using several MBs, each designed to recognize a different target, we demonstrate the selective detection of genomic cystic fibrosis related targets. Positional registration and fluorescence response monitoring of the microspheres was performed using an optical encoding scheme and an imaging fluorescence microscope system.

Base Sequence↗

Transcription initiation-defective forms of sigma(54) that differ in ability To function with a heteroduplex DNA template.

Transcription by sigma(54)-RNA polymerase holoenzyme requires an activator that catalyzes isomerization of the closed promoter complex to an open complex. We examined mutant forms of Salmonella enterica serovar Typhimurium sigma(54) that were defective in transcription initiation but retained core RNA polymerase- and promoter-binding activities. Four of the mutant proteins allowed activator-independent transcription from a heteroduplex DNA template. One of these mutant proteins, L124P V148A, had substitutions in a sequence that had not been shown previously to participate in the prevention of activator-independent transcription. The remaining mutants did not allow efficient activator-independent transcription from the heteroduplex DNA template and had substitutions within a conserved 20-amino-acid segment (Leu-179 to Leu-199), suggesting a role for this sequence in transcription initiation.

Amino Acid Substitution↗

Racial disparity in cardiac decision making: results from patient focus groups.

BACKGROUND: While numerous studies suggest that African Americans receive fewer invasive cardiac procedures than whites, the basis for these treatment differences is not understood. METHODS: We conducted focus group sessions with patients who had received treatment in the hospital or the emergency department within the preceding 3 months for ischemic heart disease at 2 urban, university-affiliated hospitals. RESULTS: Discussions with patients identified the following factors that influenced their decision making: clarity, simplicity, and consistency of treatment recommendations; advice from friends and family about whether to accept recommendations; availability to speak with others who accepted similar recommendations; and having honest and caring physicians. African American patients identified the following additional factors that influenced their decision making: perceptions of health care discrimination; perceptions of undesirable physician behavior; faith in God to control one's destiny; and patient-physician camaraderie. CONCLUSIONS: Participants identified common issues influencing health care decision making, regardless of race. However, additional factors were expressed only by African American participants. These factors conveyed racial differences in perceptions of the health care system that may, in part, contribute to differences in health care decision making and treatment.

Black or African American↗

Can raters consistently evaluate the content of focus groups?

Focus groups are increasingly being used to provide insights to researchers and policy makers. These data complement quantitative approaches to understanding the world. Unfortunately, quantitative and qualitative methodologies have often been viewed as antithetical, rather than complementary, strategies. While focus groups can clearly generate rich information that is unobtainable through other quantitative methods, it is important to determine the degree to which different raters can consistently extract information from transcripts. Thus, our goal was to quantify agreement in the interpretation of transcripts from patient and physician focus groups, using decision-making in ischemic heart disease as a model. We used data from focus groups with both patients and physicians that sought to identify factors affecting diagnostic and treatment decisions in ischemic heart disease. Three raters independently reviewed transcribed audiotapes from focus groups of patients with ischemic heart disease, as well as focus groups of physicians who care for these patients. We found that raters could not distinguish between major and minor factors reliably. More troubling, however, is that consistency regarding the apparently straightforward judgment as to the mere presence or absence of a factor was difficult to achieve. In particular, the three raters of each transcript failed to agree on between one third and one half of the factors. This reasonably high level of disagreement occurred despite the raters: (1) having generated the individual factors themselves based upon their reading a random sample of actual transcripts and (2) being trained in the use of rating forms (including standard definitions of themes). These data suggest that if a single rater evaluates focus group transcripts, as is commonly done, judgments may not be reproducible by other raters. Moreover, a single rater may not extract all important information contained in the transcripts.

Female↗

Case management programs in primary care.

To review the impact of case management programs on health care resource use; their impact on patient satisfaction, quality of life, and functional status (patient-centered outcomes); and their cost-effectiveness, we reviewed the English language literature utilizing the following MEDLINE and HealthSTAR headings: case management, patient care planning, patient-centered care, disease management, care management, and managed care programs. Bibliographies of relevant articles were also reviewed. Only randomized controlled trials were included. Data were extracted manually from relevant publications and are presented descriptively because formal, quantitative methods were not applicable. Nine studies met our inclusion criteria. Of the seven studies examining case management's impact on health resource use, only two found a positive effect. Both successful programs targeted patients with specified disease conditions and care was supervised by a medical subspecialist. None of the programs targeting general disease conditions or supervised by generalists reported a positive effect. All six studies examining patient-centered outcomes reported a positive impact. These effects were unrelated to the patient's conditions or the study personnel. Both studies examining clinical parameters found a positive impact. Only three studies examined costs; all reported nonsignificant cost savings. While case management programs offer theoretical benefits, few examples of successful programs were found. Positive effect was related to disease condition and specialty training of study personnel. Patient-centered outcomes were often improved upon but at unknown cost. Further multisite clinical trials are needed to define case management's role in our future health care system.

Case Management↗

Racial differences in cardiac catheterization use and appropriateness.

The authors sought to investigate the role of medical appropriateness as a potential explanatory factor in previously observed interracial cardiac procedure rate differences. A retrospective cohort study using RAND appropriateness criteria was conducted at a Veterans Affairs medical center among a sample of patients who were evaluated for cardiovascular disease during 1993 (n=200). All participants were men and 50% were black (mean age=61.8 years). Blacks were less likely than whites to undergo cardiac catheterizations (CC) (odds ratio [OR]=0.23, P < 0.01). When RAND criteria were applied, blacks were found to have fewer indications that made them appropriate candidates for CC and more indications making them inappropriate candidates for CC (chi-square test, P < 0.05). No CC procedure underuse was found among blacks, whereas 10% of CC overuse was found among whites. Interracial CC procedure use differences were not due to procedure underuse among blacks but were in part due to overuse among whites.

Black or African American↗

Role of duration of diuretic effect in preventing sodium retention.

OBJECTIVE: To determine whether the duration of diuretic effect at the active nephron site enhances ability to excrete an exogenous salt load. METHODS: We conducted a study that involved eight patients with New York Heart Association class II to III congestive heart failure. In a randomized, crossover manner, each patient received 3.25 mg intravenous bumetanide at 0 hours and again at 6 hours or a loading dose of 0.5 mg bumetanide at 0 hours followed by a continuous infusion of 0.5 mg/hr for 6 hours. Response was followed for 12 hours; a total of 6.5 mg of bumetanide was administered in each arm of the study. Eight hours after dosing began, we administered approximately 80 mEq sodium intravenously and examined its excretion over 4 hours. RESULTS: The percentage of the load excreted was 86% +/- 15% versus 29% +/- 30% for the infusion and bolus regimens, respectively (p = 0.0005). More bumetanide was excreted during the infusion (667 +/- 133 micrograms versus 240 +/- 121 micrograms; p = 0.0002). During the infusion, however, more sodium was excreted relative to amounts of bumetanide, indicating that the efficiency of response was greater during the infusion, 0.10 +/- 0.02 mEq sodium per microgram bumetanide versus 0.07 +/- 0.05 mEq for the bolus (p = 0.0145). CONCLUSIONS: These data support the notions that a long-acting loop diuretic maintains its efficacy and that a longer duration of action facilitates excretion of a sodium load, such as that which might occur during dietary indiscretion.

Adult↗

Examination of racial differences in management of cardiovascular disease.

OBJECTIVES: We sought to identify the clinical characteristics associated with, and to investigate the impact of cohort selection criteria on, interracial use of invasive cardiac procedures and to determine survival. BACKGROUND: Although interracial differences in the use of invasive cardiac procedures have been previously reported, the underlying reasons are not known. METHODS: A retrospective cohort study was conducted at a Veterans Affairs Medical Center. Study patients were evaluated for cardiovascular disease between January 1 and December 31, 1993. RESULTS: The study included 1,406 male patients (85% white, 58% married), with a mean age of 63.4 years. African Americans were less likely than whites to undergo procedures (cardiac catheterization: odds ratio [OR] 0.37, 95% confidence interval [CI] 0.24 to 0.58; coronary angioplasty: OR 0.60, 95% CI 0.25 to 1.49; coronary bypass surgery: OR 0.22, 95% CI 0.08 to 0.63; any procedure: OR 0.32, 95% CI 0.21 to 0.50). On bivariate analysis, patients who underwent cardiac procedures were more likely to be younger, married and reside nonlocally and less likely to have severe comorbid disease; however, African Americans were less likely to be married and to reside nonlocally and more likely to have severe comorbid disease. Cohorts adjusting for referral status and specified cardiac diagnoses reduced or reversed interracial treatment differences. Thirty-day and 1-year survival rates (96% and 87.6%, respectively) were equivalent. CONCLUSIONS: Racial disparity in invasive cardiac procedure use may be partially explained by clinical differences and cohort selection bias. Despite treatment differences, survival rates were equivalent in African Americans and whites.

Black or African American↗

Risk factors for delirium tremens development.

OBJECTIVE: To identify clinical characteristics associated with inpatient development of delirium tremens so that future treatment efforts can focus on patients most likely to benefit from aggressive therapy. DESIGN: Retrospective cohort study among patients discharged with diagnoses related to alcohol abuse. SETTING: University-affiliated inner-city hospital. PATIENTS/PARTICIPANTS: Two hundred consecutive patients discharged between June 1991 and August 1992 who underwent evaluation and treatment for alcohol withdrawal or detoxification. MEASUREMENTS AND MAIN RESULTS: Mean age was 41.9 years, 85% were male, 57% were white and 84% were unmarried. Forty-eight (24%) of the patients developed delirium tremens during hospitalization. Bivariate analysis indicated that those who developed delirium tremens were more likely to be African-American, unemployed, and homeless, and were more likely to have gone more days since their last drink, and to have concurrent acute medical illness, high admission blood urea nitrogen level and respiratory rate, and low admission albumin level and systolic blood pressure. In multiple logistic regression analyses, patients who developed delirium tremens were more likely to have gone more days since their last drink (odds ratio [OR] 1.3; 95% confidence interval [CI] 1.09, 1.61) and to have concurrent acute medical illness (OR 5.1; 95% CI 2.07, 12.55). These risk factors were combined for assessment of their ability to predict the occurrence of delirium tremens. If no factors were present, 9% developed delirium tremens; if one factor was present, 25% developed delirium tremens; and if two factors were present, 54% developed delirium tremens. CONCLUSIONS: Inpatient development of delirium tremens was common among patients treated for alcohol detoxification or withdrawal and correlated with several readily available clinical variables.

Adult↗

Effect of bovine herpesvirus-1 on expression of interleukin-2 receptors and effect of interleukin-12 on lymphocyte proliferation.

Expression of the interleukin-2 receptor alpha chain (IL-2R alpha) by peripheral blood mononuclear cells (PBMC) from Holstein calves, both experimentally-infected with bovine herpesvirus-l (BHV-l) and controls, was measured by flow cytometry. Expression of IL-2R alpha was 35 percent and 23 percent higher in infected calves than controls, on days 2 and 3 postinfection (PI), respectively. Concurrent with this increase in IL-2R alpha expression, a significant decrease (P < 0.001) was observed in the PHA-induced proliferative responses of PBMC from infected compared with control calves. In vitro treatment with recombinant human (rhu) IL-12 enhanced PHA-induced proliferative responses of PBMC from both infected and control calves. This rhuIL-12 enhancement of mitogen-induced proliferative responses was significant (P < 0.001) in infected calves on day 2 PI and was sufficient to abrogate the decrease observed due to BHV-1 infection. Since the expression of the beta and gamma chains of IL-2R was not measured it is difficult to speculate as to the status of high affinity receptor expression during BHV-1 infection. However results of the present study suggest that the decrease in proliferative responses observed during infection may not be due to a decrease in IL-2R alpha expression but may possibly be due to a selective down-regulation of signal transduction through IL-2R and/or by modulation of the expression of other cytokines involved in lymphocyte activation and proliferation.

Animals↗

A fiber-optic DNA biosensor microarray for the analysis of gene expression.

A fiber-optic biosensor array is described for the simultaneous analysis of multiple DNA sequences. A bundle of optical fibers was assembled with each fiber carrying a different oligonucleotide probe immobilized on its distal end. Hybridization of fluorescently labeled complementary oligonucleotides to the array was monitored by observing the increase in fluorescence that accompanied binding. The approach enables fast (< 10 min) and sensitive (10 nM) detection to multiple DNA sequences simultaneously, with the potential for quantitative hybridization analysis.

Biosensing Techniques↗

Demographic and epidemiological aspects of plastic surgery: profile of a supradistrict specialty.

The workload of plastic surgery is often poorly understood by the public and those responsible for financing health care. The authors have used linked statistical data to analyse demographic and epidemiological profiles of workload in plastic surgery in Oxfordshire. The analyses were constructed for residents of the district and for patients treated from other districts. The former provides a profile of workload generated for plastic surgery from a geographically-defined population. The latter complements this by adding information about 'imported' workload. Admission rates for plastic surgery were higher for children and elderly people than for other age groups; higher for males than females; and they increased during the 11 years of the study. Most of the increase represented an increase in people treated by the service, rather than an increase in readmissions, although there was a modest increase in the latter too. Lengths of stay per admission and total time spent in hospital per person declined considerably. The bulk of the workload in plastic surgery is concerned with the treatment of trauma (including burns), cancer and congenital malformations. The main clinical conditions treated by the specialty are documented distinguishing, for each condition, the extent to which the patients came from outside the authority in which the provider unit is cited.

Adolescent↗

Effect of stress on interleukin-2 receptor expression by bovine mononuclear leukocytes.

Holstein calves given three consecutive i.m. injections of dexamethasone (DEX) (0.04 mg kg-1) showed lymphopenia and neutrophilia with increased numbers of mature neutrophils on post-injection Days 1 and 2, but these values returned to normal levels by post-injection Day 3. Interleukin-2 receptor (IL-2R) expression by peripheral blood mononuclear cells (PBMC) was evaluated by flow cytometry using a monoclonal antibody specific for bovine IL-2R alpha. Treatment with DEX significantly decreased expression of IL-2R alpha in Concanavalin A (Con A)-activated PBMC on Day 1 (P < 0.02) and on Day 2 (P < 0.1). On Day 3, expression of IL-2R alpha by PBMC was similar in control and DEX-treated calves. This decrease in IL-2R alpha expression correlated with decreased proliferative responses of PBMC to the T-cell mitogens, phytohemagglutinin (PHA) and Con A. Following in vitro treatment with recombinant human (rhu) interleukin-12 (IL-12) Con A-induced proliferative responses of PBMC tended to be higher in both groups. However, the rhu IL-12 induced increase of Con A activated proliferative responses were significantly greater in DEX-treated calves than in control calves. IL-2R alpha expression by PBMC was found to be less in calves transported 800 km in a truck as compared to that in PBMC from controls. These data suggest that stress-induced immunosuppression in calves may involve decreased IL-2R alpha expression and decreased IL-12 production. Serum chemistry results indicated a trend toward higher creatine kinase (CK) levels in DEX-treated calves. This may be due to the lysis of corticosteroid sensitive lymphocytes.

Animals↗