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Biomedical subjects

B R Davis

Publications and source records attributed to B R Davis.

At least 73 records · Page 4Linked to original sources

Lack of effectiveness of a low-sodium/high-potassium diet in reducing antihypertensive medication requirements in overweight persons with mild hypertension. TAIM Research Group. Trial of Antihypertensive Interventions and Management.

The Trial of Antihypertensive Interventions and Management (TAIM) was a multicenter randomized drug (double-blind, placebo-controlled)-diet trial. One objective of TAIM was to assess the long-term ability of a low-sodium/high-potassium (Na+ decreases/K+ increases) diet to maintain blood pressure control in persons at 110% to 160% ideal weight with diastolic blood pressure from 90 to 100 mm Hg who were on no drugs or on low-dose monotherapy. Participants, 56% men and 33% black, were randomized to usual diet (n = 296) or to Na+ decreases/K+ increases diet (n = 291) and within each diet group to placebo, 25 mg/day chlorthalidone, or 50 mg/day atenolol. Treatment failure was defined as lack of blood pressure control requiring additional drugs according to specified criteria. At baseline, the mean value for age was 48 years; blood pressure, 143/93 mm Hg; weight, 88 kg; and 24-h urinary sodium and potassium excretion rates, 133 and 57 mmol/day, respectively. At 3 years, the net difference in 24-h urinary sodium/potassium excretion rates between the Na+ decreases/K+ increases and the usual diet groups was -30 and +11 mmol/L/day. The relative risk of treatment failure for Na+ decreases/K+ increases compared to usual diet by proportional hazards regression was 0.95 (P = .71). This study provides no support for the sole use of a low-sodium/high-potassium diet as a practical therapeutic strategy in maintaining blood pressure control in the moderately obese.

Adult↗

Uniformity of captopril benefit in the SAVE Study: subgroup analysis. Survival and Ventricular Enlargement Study.

The Survival and Ventricular Enlargement (SAVE) Study demonstrated that long-term administration of the angiotensin-converting enzyme inhibitor captopril to recent survivors of myocardial infarction with left ventricular dysfunction resulted in a reduction in cardiovascular mortality and morbidity. Analysis of multiple subgroups demonstrated that baseline demographics (older age) and clinical characteristics (such as prior MI, history of diabetes or hypertension), that have previously been associated with a higher risk of cardiovascular events, were associated with greater end point event rates in SAVE regardless of therapy assignment at the time of randomization. The effectiveness of captopril therapy in reducing cardiovascular mortality and morbidity was examined in multiple subgroups. Although not all subgroups provided adequate statistical power, the benefits of captopril therapy were relatively uniform in the SAVE study. This indicates that the benefits were not confined to one particular subgroup and conversely that targeting of captopril therapy should be to the broadest group, as defined by SAVE entry criteria, to result in a reduction in cardiovascular mortality and morbidity.

Captopril↗

Effects of captopril on ischemic events after myocardial infarction. Results of the Survival and Ventricular Enlargement trial. SAVE Investigators.

BACKGROUND: In the Survival and Ventricular Enlargement (SAVE) trial, recurrent myocardial infarction (MI) was the most important predictor of a poor outcome and conferred a sevenfold increase in risk of death. The purpose of this study was to determine the predictors of recurrent MI in study participants and to examine the influence of the angiotensin-converting enzyme inhibitor captopril on this and other myocardial ischemic events. METHODS AND RESULTS: The 2231 patients had survived the acute phase of MI (3 to 16 days) and had a radionuclide ventricular ejection fraction < or = 40%. Patients were randomly assigned to receive double-blind treatment with either placebo or captopril and were followed for an average of 42 months. The influence of captopril on recurrent MI, cardiac revascularization procedures, and hospitalization with unstable angina was examined. The likelihood of recurrent MI was greater in patients with an MI or functional disability before the index infarction and higher systolic pressure (all P < .001) but was not influenced by baseline left ventricular ejection fraction. Therapy with captopril reduced the risk of development of recurrent MI by 25% (95% confidence intervals, 5% to 40%; P = .015) and the risk of death after recurrent MI by 32% (95% confidence intervals, 4% to 51%; P = .029). Captopril-assigned patients were also less likely to require cardiac revascularization procedures (P = .010), but hospitalization for unstable angina was unaltered. When all three of these major coronary ischemic events were considered together, captopril therapy reduced the risk (14% risk reduction; 95% confidence intervals, 0% to 26%; P = .047). CONCLUSIONS: In post-MI patients with asymptomatic left ventricular dysfunction, long-term administration of captopril reduced recurrence of MI and the need for cardiac revascularization but had no influence on the rate of hospitalization with a discharge diagnosis of unstable angina. The finding that the recurrence of MI was independent of left ventricular ejection fraction suggests that captopril could be useful in preventing recurrent MI in patients with more preserved left ventricular function. The need for cardiac revascularization was reduced in patients receiving long-term captopril therapy, suggesting either an anti-ischemic effect or the ability of the angiotensin-converting enzyme inhibitor to modify the atherosclerotic process in survivors of MI.

Angina, Unstable↗

Colonic complications of pancreatitis.

A retrospective review of 296 patients referred for surgical management of pancreatitis from 1964 to 1992 revealed that 18 (6.1%) had colonic complications. Of seven patients with chronic pancreatitis, six developed pancreatocolonic fistulas. One had stenosis of the transverse colon, which resolved after pancreatic cystjejunostomy, three were managed with local fistula excision and simple colon closure, three had segmental colectomy, and in one the fistula closed spontaneously with expectant management. Three patients had concomitant lateral pancreaticojejunostomy, and two had a cystjejunostomy. There were two postoperative complications, but no mortality. Eleven patients had acute necrotizing pancreatitis. Seven developed segmental colonic infarction that required partial colectomy. Four had colonic fistulas, two managed with partial colectomy and colostomy, and two managed nonoperatively. Eleven patients developed major postoperative complications; four died, two from sepsis and multiorgan failure and two from recurrent hemorrhage from a necrotic pancreatic bed. Our findings indicate that the presentation, management, and outcome of colonic complications differ in chronic and acute pancreatitis. In chronic pancreatitis, pancreatocolonic fistula predominated and could be managed either with local excision or segmental resection of the colon with excellent results. Simultaneous surgical correction of associated pancreatic pathology was possible in five patients. In acute necrotizing pancreatitis, colonic infarction secondary to the necrotizing inflammatory process was frequent and required colon resection. There was substantial morbidity and mortality in spite of treatment with colectomy.

Acute Disease↗

Stafne bone defect.

Explore the source record for details and available documents.

Diagnosis, Differential↗

The purification and characterization of an extremely thermostable alpha-amylase from the hyperthermophilic archaebacterium Pyrococcus furiosus.

The alpha-amylase from Pyrococcus furiosus, a hyperthermophilic archaebacterium, has been purified to homogeneity. The enzyme is a homodimer with a subunit molecular mass of 66 kDa. The isoelectric point is 4.3. The enzyme displays optimal activity, with substantial thermal stability, at 100 degrees C, with the onset of activity at approximately 40 degrees C. Unlike mesophilic alpha-amylases there is no dependence on Ca2+ for activity or thermostability. The enzyme displays a broad range of substrate specificity, with the capacity to hydrolyze carbohydrates as simple as maltotriose. No subtrate binding occurs below the temperature threshold of activity, and a decrease in Km accompanies an increase in temperature. Except for a decrease in Asp and an increase in Glu, the amino acid composition does not confirm previously defined trends in thermal adaption. Fourth derivative UV spectroscopy and intrinsic fluorescence measurements detected no temperature-dependent structural reorganization. Hydrogen exchange results indicate that the molecule is rigid, with only a slight increase in conformational flexibility at elevated temperature. Scanning microcalorimetry detected no considerable change in the heat capacity function, at the pH of optimal activity, within the temperature range in which activity is induced. The heat absorption peak due to denaturation, under these conditions, occurred within the temperature range of 90-120 degrees C. When the pH was increased, a change in the shape of the heat absorption peak was observed, which when analyzed thermodynamically shows that the process of heat denaturation is complex, and includes at least three stages, indicating that the protein structure consists of three domains. At temperatures below 90 degrees C no excess heat absorption or change in the CD spectra were observed which could be associated with the cooperative conformational transition of the protein. According to the thermodynamic characteristics of the heat denaturation, the cold denaturation of this protein can be expected only at -3 degrees C. Therefore, the observed inactivation of this enzyme is not caused by the cooperative change of its tertiary structure. It can be associated only with the gradual changes of protein domain interaction.

Amino Acid Sequence↗

Reduction in long-term antihypertensive medication requirements. Effects of weight reduction by dietary intervention in overweight persons with mild hypertension.

BACKGROUND: Increasing concern over long-term drug treatment of mild hypertension has stimulated several studies of weight reduction. Phase I of the Trial of Antihypertensive Interventions and Management demonstrated a short-term effect of weight loss on blood pressure control in overweight persons with mild hypertension, who were either taking placebo or taking low-dose monotherapy. Phase II investigates the long-term benefit of weight loss on the ability to maintain blood pressure control. METHODS: From 10148 community-based screenees, 587 persons (5.8%), aged 21 to 65 years, entered a multicenter, randomized drug (double-blind, placebo-controlled) and diet trial. Participants had a diastolic blood pressure between 90 and 100 mm Hg and were at 110% to 160% of their ideal weight. They were randomized to a usual diet (n = 296) or to a weight loss diet (n = 291) and within each diet group to placebo, chlorthalidone, 25 mg/d, or atenolol, 50 mg/d. Treatment failure was defined as using additional antihypertensive medications if diastolic blood pressure rose above 90 mm Hg according to protocol-specified criteria. RESULTS: At baseline, mean diastolic blood pressure was 93 mm Hg; systolic blood pressure, 143 mm Hg; weight, 88 kg; percent ideal weight, 137%; age, 48 years; 56% were men; and 33% were black. Mean follow-up was 4.5 years. There was a net loss of 2 to 3 kg with weight loss diet compared with usual diet over most of the follow-up period. The 5-year incidence of treatment failure was 56.7 per 100 participants with usual diet and 49.8 per 100 with weight loss. Long-term weight loss decreased failure of blood pressure control for those receiving placebo or low-dose diuretic or beta-blocker by 23%. The results were similar in direction in each drug group. CONCLUSIONS: The Trial of Antihypertensive Interventions and Management demonstrated that weight reduction is an effective long-term therapy for maintaining blood pressure in the normal range when used as monotherapy or in combination with either thiazide diuretics or beta-blockers. Consequently, weight loss should be recommended for the management of obese individuals with mild hypertension.

Adult↗

Trial of antihypertensive intervention and management: greater efficacy with weight reduction than with a sodium-potassium intervention.

The Trial of Antihypertensive Intervention and Management evaluated nine diet-drug combinations in 878 mildly hypertensive, moderately obese participants using a 3 x 3 factorial design. Drugs evaluated were placebo, diuretic (chlorthalidone), and beta-blocker (atenolol); diets were usual (no intervention), weight reduction, and low sodium/high potassium (Na/K). This article reports 6-month dietary changes and the effect of dietary change on blood pressure. Six-month mean weight change was -4.7 kg in the weight reduction group, -0.3 kg in the Na/K group, and -0.5 kg in the usual-diet group. At 6 months, daily electrolyte excretion had changed in the Na/K intervention group. Daily sodium excretion decreased from 138.0 to 112.0 mmol in the Na/K group and increased from 134.1 to 138.4 mmol in the weight reduction group and from 129.1 to 137.0 mmol in the usual-diet group. Daily potassium output increased from 58.7 to 71.4 mmol in the Na/K group, from 57.0 to 60.5 mmol in the weight reduction group, and from 55.3 to 59.1 mmol in the usual diet group. Analysis of 3-day food records indicated that sodium intake decreased from 141.1 to 85.8 mmol and potassium intake increased from 76.4 to 90.5 mmol. Our results indicate that the goal for weight reduction was more easily achieved than the goal for electrolyte modification.

Adult↗

A method for obtaining repeatable measurements of the tensile properties of skin at low strain.

Initial attempts at measuring the low strain tensile properties of skin led to results which were not repeatable. It appeared that strains induced in the sample due to the handling needed to mount it in a simple clamp led to the low precision of the test. A new method which minimized the manipulation needed to mount a sample in a testing machine was then developed. Using this method the skin was aligned with a set of grips in a saline bath. When aligned, the saline was removed and the sample clamped in the grips without the need for additional handling. This approach produced a marked improvement in the repeatability of the tensile properties of skin at low strains.

Animals↗

Statistical considerations in monitoring the Systolic Hypertension in the Elderly Program (SHEP).

The Systolic Hypertension in the Elderly Program (SHEP), a randomized, double-masked, placebo-controlled trial of 4736 persons, was designed to assess the efficacy of antihypertensive drug treatment to reduce the risk of fatal and nonfatal strokes among people age 60 and over with isolated systolic hypertension. The statistical method used in interim monitoring of results was conditional power (or stochastic curtailment). The findings did not become conclusive until near the completion of the trial, and therefore SHEP was continued to its scheduled closing date. The trial demonstrated a 36% reduction in the incidence of stroke in the active treatment group (P = .0003). In addition to evaluating overall efficacy of treatment, the monitoring process considered such other issues as nonstroke outcomes, lag time between first report of stroke and final confirmation of stroke diagnosis, consistency of results across subgroups, and completeness of follow-up. The purpose of this article is to review these factors with primary emphasis on the statistical aspects.

Aged↗

Differences in precision of dietary estimates among different population subgroups.

Populations vary in consistency of diets. The precision of estimates (E) of nutrient intake depends both on the ratio (R) of intraindividual to interindividual variances, as well as on the number of days of dietary intake recorded (k). We present baseline data from 872 participants in the Trial of Antihypertensive Interventions and Management (TAIM), a randomized clinical trial of diet and drug treatment for mild hypertension. There is wide variation in R among different demographic groups and for different nutrients. This has implications for the ability to estimate the correlations between the nutrient and a physiologic variable such as blood pressure, as well as for power calculations to compare group means on nutrient intake. For example, to achieve the same degree of precision (E = 0.80) in estimating the correlation between sodium intake and blood pressure for whites in New York, 7 days of food records would be required, compared to 2 days for whites in Alabama. Tables are presented indicating within- and between-person variances for different groups and different nutrients. Methods of calculating E, determining k, and calculating samples size are provided. Investigators designing nutritional epidemiologic studies should take into account ratios of intraindividual to interindividual variances of different population subgroups and different nutrients in order to determine the number of daily food records that must be obtained and the sample size for group comparisons.

Adult↗

Effect of different human immunodeficiency virus type-1 (HIV-1) isolates on long-term bone marrow haemopoiesis.

Haemopoietic cytopenias are a frequent occurrence in human immunodeficiency virus type-1 (HIV-1) induced disease. In order to examine the possible direct inhibition of marrow haemopoiesis by HIV-1, we have investigated the effect of HIV-1 infection on myelopoiesis in long-term bone marrow cultures. In vitro exposure of normal marrow cultures to three different lymphocytotropic HIV-1 isolates resulted in productive infection, as demonstrated by a progressive increase of gag p24 antigen. In these experiments, ICR-3 isolate, but not LAV' or NL4-3 isolates, accelerated the loss of non-adherent cells. A differential ability of these HIV-1 isolates to suppress myelopoiesis was confirmed in long-term cultures in which virus was added continuously. In these cultures, ICR-3, and to a lesser extent also NL4-3, but not LAV', induced a progressive decrease in the number of total non-adherent cells as well as non-adherent colony forming units-granulocyte/macrophage (CFU-GM). Furthermore, exposure of normal purified CD34+ cells to ICR-3 induced defects in their ability to form haemopoietic colonies; this inhibitory effect was significantly relieved by pretreatment of ICR-3 with an anti-gp120 antibody. Similar exposure of CD34+ cells to LAV' and NL4-3 induced no such defects. These data indicate that some HIV-1 isolates can impair bone marrow haemopoiesis in a dose-dependent fashion, acting, at least in part, at the level of haemopoietic stem/progenitor cells.

Antigens, CD↗

Conclusions and implications of the systolic hypertension in the elderly program.

Isolated systolic hypertension has a higher prevalence with age and an associated excess cardiovascular risk. The Systolic Hypertension in the Elderly Program (SHEP) was a randomized, prospective, double blind clinical trial to assess the efficacy and safety of a antihypertensive regimen based on low dose diuretic therapy in reducing the five year combined incidence of fatal and nonfatal stroke. SHEP demonstrated a significant 36% reduction in stroke incidence. Also, 27% reduction in coronary heart disease incidence and a 32% reduction in major cardiovascular disease incidence were achieved. The benefits accrued to all subgroups identified based on baseline age, race, sex, blood pressure, serum cholesterol levels, and ECG abnormalities. A low-dose diuretic regimen should be the initial treatment of choice for most hypertensive patients, based on demonstrated reduction in risk for major cardiovascular events, its safety, acceptance by patients, and low cost.

Age Factors↗

Comparison of two devices for wound measurement.

Sixty leg ulcers were measured with two techniques, a common paper tape measure and a new technique, a plastic grid device. The plastic grid proved to be a reliable, valid, and feasible method to quickly assess wounds in a busy outpatient setting. The grid was superior to the tape measure in assessing large and/or irregular ulcers.

Clinical Nursing Research↗

tat protein stimulates production of transforming growth factor-beta 1 by marrow macrophages: a potential mechanism for human immunodeficiency virus-1-induced hematopoietic suppression.

In this study, we examined the potential role of the human immunodeficiency virus (HIV) tat protein in causing the hematopoietic abnormalities frequently observed in HIV-infected individuals. Recombinant tat (r-tat) protein, at concentrations up to 10 micrograms/mL, did not display any stimulatory or inhibitory effect on the survival/proliferative capacity of CD34+ hematopoietic progenitor cells, purified from normal bone marrow (BM). However, exposure of r-tat protein (at concentrations between 10 ng/mL and 10 micrograms/mL) to enriched normal BM macrophages induced the production of a factor(s) in conditioned media that inhibited the in vitro growth of CD34+ cells in liquid cultures and of immature hematopoietic progenitors (day 14 colony-forming unit-granulocyte-macrophage, burst-forming unit-erythroid, and colony-forming unit-megakaryocyte) in semisolid assays. Pre-exposure of r-tat protein with a monoclonal neutralizing anti-tat antibody completely abrogated the inhibitory activity present in BM macrophage culture supernatants. The main factor responsible for this suppressive activity was transforming growth factor-beta 1 (TGF-beta 1), as shown by the ability of a polyclonal anti-TGF-beta 1 neutralizing antibody to almost completely reverse the suppressive effect of BM macrophage supernatants on CD34+ cells. TGF-beta 1 bioassays showed that exposure of r-tat protein to BM macrophages significantly increased the levels of both active and latent forms of TGF-beta 1. These results indicate that the production of TGF-beta 1, one of the most potent negative regulator of hematopoiesis, is increased by HIV tat protein and that such increase could contribute to the derangement of the hematopoietic system in HIV-infected individuals.

Antibodies↗

Analysis of a clinical trial involving a combined mortality and adherence dependent interval censored endpoint.

Clinical trials often involve a variety of clinical and laboratory measures that are used as endpoints and sometimes two of these measures are combined in one endpoint. When the individual components of such a combined endpoint are 'time to event' measurements, the analysis is straightforward if each of the components is measured frequently and regularly over time. However, the analysis of the combined endpoint is more difficult when one component of the endpoint is right censored and the other is interval censored. This paper describes a statistic, based on a rank ordering of events for such a combined measure. The power of the test statistic is explored.

Clinical Trials as Topic↗