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Biomedical subjects

B R Davis

Publications and source records attributed to B R Davis.

At least 91 records · Page 5Linked to original sources

Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators.

BACKGROUND: Left ventricular dilatation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, longterm therapy with the angiotensin-converting--enzyme inhibitor captopril attenuated ventricular dilatation and remodeling. We investigated whether captopril could reduce morbidity and mortality in patients with left ventricular dysfunction after a myocardial infarction. METHODS: Within 3 to 16 days after myocardial infarction, 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were randomly assigned to receive doubleblind treatment with either placebo (1116 patients) or captopril (1115 patients) and were followed for an average of 42 months. RESULTS: Mortality from all causes was significantly reduced in the captopril group (228 deaths, or 20 percent) as compared with the placebo group (275 deaths, or 25 percent); the reduction in risk was 19 percent (95 percent confidence interval, 3 to 32 percent; P = 0.019). In addition, the incidence of both fatal and nonfatal major cardiovascular events was consistently reduced in the captopril group. The reduction in risk was 21 percent (95 percent confidence interval, 5 to 35 percent; P = 0.014) for death from cardiovascular causes, 37 percent (95 percent confidence interval, 20 to 50 percent; P less than 0.001) for the development of severe heart failure, 22 percent (95 percent confidence interval, 4 to 37 percent; P = 0.019) for congestive heart failure requiring hospitalization, and 25 percent (95 percent confidence interval, 5 to 40 percent; P = 0.015) for recurrent myocardial infarction. CONCLUSIONS: In patients with asymptomatic left ventricular dysfunction after myocardial infarction, long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events. These benefits were observed in patients who received thrombolytic therapy, aspirin, or beta-blockers, as well as those who did not, suggesting that treatment with captopril leads to additional improvement in outcome among selected survivors of myocardial infarction.

Adult↗

Isolation and molecular characterization of the human CD34 gene.

The human CD34 surface antigen is selectively expressed on hematopoietic stem/progenitor cells, suggesting that it plays an essential role in early hematopoiesis. Using a 1.5-kb partial human CD34 cDNA sequence, RNA-polymerase chain reaction (PCR), and rapid amplification of cDNA ends (RACE) methods, we cloned and sequenced the full-length (2.65 kb) cDNA. The cDNA encodes a type I transmembrane protein with no obvious homology to other known proteins. The entire CD34 gene of 28 kb was cloned, and the coding sequences mapped to eight exons. Mapping of the 5' termini of mRNAs by 5'-RACE and RNAase protection analyses has indicated that the human CD34 gene uses multiple transcription initiation sites. Analysis of the upstream regulatory sequences revealed the absence of TATA and CAAT box sequences, and the presence of myb, myc, and ets-like DNA binding motifs. We have identified significant homology between human and mouse CD34 genes in 5' and 3' untranslated regions, amino acid coding sequences, and 5' flanking sequences. This investigation of the CD34 gene should facilitate study of the function and regulation of this stem cell antigen.

Amino Acid Sequence↗

Effect of antihypertensive therapy on weight loss. The Trial of Antihypertensive Interventions and Management Research Group.

We report the effect of weight changes of the type of antihypertensive medication prescribed in a trial of the relative efficacy of drug and dietary measures in mild hypertension. The Trial of Antihypertensive Interventions and Management studied 878 mildly hypertensive individuals randomly assigned, in a 3 x 3 design, to no diet change, weight loss, or a low sodium-high potassium diet and to placebo, 25 mg chlorthalidone, or 50 mg atenolol. The type of drug prescribed affected weight change with all diets. The drug effect on weight change, present in all groups at 6 months, was most pronounced in those randomly assigned to the weight loss diet, where the placebo group lost 4.4 kg, the atenolol group lost 3.0 kg, and the chlorthalidone group lost 6.9 kg. The group differences were attenuated but persisted at 24 months. We suggest that the antihypertensive drug prescribed affects the success of a conjoint weight loss program and speculate that the difference between the drugs may be due to their intrinsic effects on the sympathetic nervous system and related metabolic changes.

Atenolol↗

The Trial of Antihypertensive Interventions and Management (TAIM) study. Adequate weight loss, alone and combined with drug therapy in the treatment of mild hypertension.

This report examines the effect of weight loss, alone and in combination with drugs, on diastolic blood pressure change in the Trial of Antihypertensive Interventions and Management (TAIM), which is a randomized, multicenter, placebo-controlled clinical trial of drug and diet combinations in the treatment of mild hypertension among 787 patients. Diastolic blood pressure drop (11.6 mm Hg) at 6 months among those patients who were randomized to weight reduction and placebo drug treatment was greater among those who lost 4.5 kg or more, than the 7-mm Hg drop for those who lost less than 2.25 kg or for the placebo-treated control group, and it was statistically equivalent to the reduction achieved by 25 mg of chlorthalidone or 50 mg of atenolol (11.1- and 12.4-mm Hg drop, respectively). Weight loss potentiated effects of drugs, with reductions of 18.4 mm Hg, for those patients who were taking atenolol and had a 4.5-kg or more weight loss, and of 15.4 mm Hg, for those patients who were taking chlorthalidone and had at least a 2.25-kg weight loss. We concluded that effective weight loss (greater than or equal to 4.5 kg) lowers blood pressure similarly to low-dose drug therapy and potentiates drug effects, with the apparent 4.5-kg threshold being lowered to 2.25 kg for those patients who receive chlorthalidone.

Atenolol↗

Effect of antihypertensives on sexual function and quality of life: the TAIM Study.

OBJECTIVE: To evaluate treatment of mild hypertension using combinations of diet and low-dose pharmacologic therapies. DESIGN: Multicenter, randomized, placebo-controlled clinical trial. SETTING: Three university-based tertiary care centers. PATIENTS: Patients (697) 21 to 65 years of age with diastolic blood pressure between 90 and 100 mm Hg as well as weight between 110% and 160% of ideal weight. INTERVENTION: Patients were stratified by clinical center and race and were randomly assigned to one of three diets (usual, low-sodium and high-potassium, weight loss) and one of three agents (placebo, chlorthalidone, and atenolol). MEASUREMENTS: Changes in measures of sexual problems, distress, and well-being after 6 months of therapy were analyzed. MAIN RESULTS: Low-dose chlorthalidone and atenolol produced few side effects, except in men. Erection-related problems worsened in 28% (95% CI, 15% to 41%) of men receiving chlorthalidone and usual diet compared with 3% (CI, 0% to 9%) of those receiving placebo and usual diet (P = 0.009) and 11% (CI, 2% to 20%) of those receiving atenolol and usual diet (P greater than 0.05). The weight loss diet ameliorated this effect. The low-sodium diet with placebo was associated with greater fatigue (34%; CI, 23% to 45%) than was either usual diet (18%; CI, 10% to 27%; P = 0.04) or weight reduction (15%; CI, 7% to 23%; P = 0.009). The low-sodium diet with chlorthalidone increased problems with sleep (32%; CI, 22% to 42%) compared with chlorthalidone and usual diet (16%; CI, 8% to 24%; P = 0.04). The weight loss diet benefited quality of life most, reducing total physical complaints (P less than 0.001) and increasing satisfaction with health (P less than 0.001). Total physical complaints decreased in 57% to 76% of patients depending on drug and diet group, and were markedly decreased by weight loss. CONCLUSION: In general, low-dose antihypertensive drug therapy (with chlorthalidone or atenolol) improves rather than impairs the quality of life; however, chlorthalidone with usual diet increases sexual problems in men.

Adult↗

Dynamic measurement of the viscoelastic properties of skin.

A wave propagation technique was used to measure the dynamic viscoelastic properties of excised skin when subjected to a low incremental strain. The propagation velocity, attenuation, and storage and loss moduli were determined from measured characteristics of a pulse propagating along a strip of skin. Experiments were conducted with the skin subjected to static stresses of 1500 Pa and 20,000 Pa. At low static stresses the skin response was viscoelastic with a loss tangent of approximately 0.6. In the frequency range of 0-1000 Hz, the wave velocity was relatively constant while the attenuation increased roughly linearly with frequency. However, results depended on the static stress. At the higher stress level the velocity was greater and the attenuation less than at the lower stress. At low stresses both the storage and loss moduli were relatively constant over the frequency range tested. The strong viscoelastic behavior of the tissue at higher frequencies is not predicted from models of the tissue determined from quasi-static test methods. In selecting a model to describe the behavior of skin, the test methods used for establishing the model must be consistent with its intended application.

Animals↗

Operational aspects of terminating randomization in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) is a randomized clinical trial sponsored by the National Eye Institute (NEI) designed to test whether cryotherapy applied to eyes of premature infants with a specified extent of stage 3+ ROP significantly decreases the incidence of an unfavorable outcome. An unfavorable outcome is defined as either retinal detachment or a retinal fold and was determined at 3 months posttreatment by the use of a masked photographic system. Enrollment into the trial was terminated on recommendation of the Data and Safety Monitoring Committee 9 months before the scheduled closing date for enrollment because of demonstrated treatment benefit. The purpose of this article is to discuss the operations involved in the orderly termination of enrollment and dissemination of results from this trial. These activities included preparation of trial participants and staff, release of trial information, continuing patient care, data collection and coding, and publication of trial results.

Blindness↗

Statistical considerations in terminating randomization in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) was a randomized trial designed to test whether cryotherapy applied to the retina significantly decreased the incidence of retinal detachment, retinal fold, or retrolental "mass." Randomization into the trial was terminated on recommendation of the Data and Safety Monitoring Committee 9 months before the scheduled end of the intake period. At the time of the decision, a favorable outcome at 3 months posttreatment occurred more frequently in eyes treated with cryotherapy (78%) as compared to untreated eyes (57%) (chi 2 = 20.5). The basic statistical method used in monitoring the results was conditional power (or stochastic curtailment). Several other issues were considered in deciding to terminate the trial, including the examination of results across subgroups and clinical centers, the completeness of follow-up, clinical assessment of outcome, and long-term consequences of the treatment.

Bias↗

Visual acuity in infants after vitrectomy for severe retinopathy of prematurity.

During the course of the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP), 98 infants (129 eyes) from the randomized segment of the trial developed total retinal detachment from retinopathy of prematurity (ROP) before the 1-year examination. The authors report as a case series the results of acuity card assessment of monocular grating acuity at 1 year in 53 infants (71 eyes) postvitrectomy and in 45 infants (58 eyes) who had retinal detachments but who did not undergo retinal reattachment surgery. The decision to undertake and the surgical technique used for a retinal reattachment procedure was not part of the randomized CRYO-ROP trial. Two eyes of one infant had pattern vision at the lowest measurable threshold after vitrectomy. None of the remaining eyes that had undergone vitrectomy and none of the eyes that did not undergo vitrectomy showed evidence of pattern vision. The relatively poor visual outcomes in this case series suggest that efforts are well-spent in attempting to prevent retinal detachment in ROP.

Cryosurgery↗

Enhancement of human immunodeficiency virus type 1 infection by cationic liposomes: the role of CD4, serum and liposome-cell interactions.

We have reported previously the enhancement of the infectivity of human immunodeficiency virus type 1 (HIV-1) by liposomes composed of the cationic lipid N-[2,3-(dioleyloxy) propyl]-N,N,N-trimethylammonium chloride (DOTMA). To determine the mechanism by which this process occurs, we have investigated the role of CD4, serum concentration and liposome-cell interactions in the DOTMA-mediated stimulation of HIV-1 infection of A3.01 cells. Serum alone significantly inhibited the binding and infectivity of HIV-1, but DOTMA-mediated enhancement of infectivity was more pronounced in the presence of serum than in its absence. HIV-1 binding to cells was increased in the presence of DOTMA liposomes, DEAE-dextran and polybrene, all of which also enhanced infectivity to a similar extent at comparable concentrations. Fluorescence dequenching measurements indicated that DOTMA liposomes fused with HIV-1, but not with cell membranes, in the presence of serum. The enhancing effect of DOTMA liposomes on HIV-1 infectivity was CD4-dependent, and appeared to involve virus-liposome fusion and liposome binding to the cell surface. DOTMA liposomes did not mediate infection of the CD4-K562 and Raji cell lines.

Antibodies, Monoclonal↗

Patterns of glycosaminoglycan/proteoglycan immunostaining in human skin during aging.

Proteoglycans and their component glycosaminoglycans are involved in such cell-cell and cell-matrix interactions as cell adhesion and migration, processes that are essential for embryonic and fetal development. As definitive organs such as skin emerge, structurally different proteoglycans partition into highly defined compartments. In skin, these compartments correspond to morphologically and functionally distinct layers. However, during the normal aging process, the relative amounts of structurally distinct proteoglycans apparently varies independently in each of these layers. This was demonstrated, in an indirect immunocytochemical study, through the use of monoclonal antibodies that detect structurally distinct domains in glycosaminoglycan chains of proteoglycans. Using samples of normal human skin obtained from individuals ranging in age from 20 weeks of gestation to 98 years of age, we determined that a common distribution pattern existed in skin. The epidermis contained chondroitin 4- and keratan sulfates, the basal lamina was the only layer that contained chondroitin 6-sulfate, the papillary and reticular dermis contained principally dermatan sulfate. In addition, antibodies that recognize native domains in chondroitin sulfates identified proteoglycan subsets that partitioned into distinct layers. An important new finding was that the relative amounts of specific types of glycosaminoglycans varied in an age- and layer-dependent manner. In the epidermis there was a notable increase in keratan sulfate beginning at age 50. Chondroitin 6-sulfate, found principally in the basal lamina, decreased after age 60. In the papillary dermis, the amount of dermatan sulfate increased after age 50, whereas the amount of novel chondroitin sulfate epitope, detected by antibody 4C3, decreased with age. Thus, age-related changes in proteoglycan distribution exist and correlate with morphologic and functional changes that occur in the intrinsic process of aging in human skin.

Adolescent↗

Prevalence of postural hypotension at baseline in the Systolic Hypertension in the Elderly Program (SHEP) cohort.

OBJECTIVE: The objective of this study was to examine the prevalence and correlates of postural hypotension (defined as a drop in systolic blood pressure of greater than or equal to 20 mm Hg) in a cohort of elderly persons with isolated systolic hypertension (ISH). DESIGN: Baseline cross-sectional analysis of the 4,736 persons randomized in the Systolic Hypertension in the Elderly Program (SHEP). SETTING: A randomized multi-center double-blind outpatient clinical trial of the impact of treating ISH. PARTICIPANTS: Men and women age greater than or equal to 60 years with the systolic blood pressure (SBP) greater than or equal to 160 mm Hg and diastolic blood pressure (DBP) less than 90 mm Hg. MEASURES: Medical histories were obtained using interviewer-administered, standardized clinical history forms. At entry into the study, seated and standing BP was measured by certified BP technicians using a random zero sphygmomanometer. Postural hypotension (PH) was assessed at 1 and 3 minutes after the participant arose from a seated position. MAIN RESULTS: PH was found in 10.4% of participants at 1 minute and in 12.0% of participants at 3 minutes. 5.3% of participants demonstrated PH at both time intervals while 17.3% demonstrated PH at either or both of the time intervals. Factors significantly (P less than 0.05) associated with the presence of PH were higher mean SBP and a lower mean body mass index. CONCLUSIONS: Somewhat different persons were defined as having PH based upon the 1 minute and 3 minute standing measures of BP, and prevalence estimates of PH can vary depending on whether one or more intervals of measurement are used. Cross-sectional data analysis indicated that PH, in healthy community-dwelling older persons with ISH, may not be associated with a history of disorders or problems usually thought to be related to PH. However, prospective data are needed to determine the prognostic significance of PH, and whether one or multiple measurements carry more significance.

Aged↗

The effects of layer properties on shear disturbance propagation in skin.

The effects of the stratum corneum and dermis on shear wave propagation along the skin surface was investigated using a mathematical model. The skin was modeled as two distinct viscoelastic layers, one representing the stratum corneum and the other representing the dermis. The layers were supported by a semi-infinite visco-elastic half-space representing the subcutaneous fat. Physical and mechanical properties of the materials in the model were determined from the literature and from our own experimental measurements. Although the stratum corneum is very thin (12-15 microns), results showed that it could have a strong effect on the wave propagation due to its high stiffness relative to the dermis. Results of the analysis are discussed with respect to an experimental procedure used to determine age-related changes in mechanical properties of skin.

Aging↗

Absent or rare human immunodeficiency virus infection of bone marrow stem/progenitor cells in vivo.

An important question in human immunodeficiency virus (HIV) pathogenesis is whether HIV-infected bone marrow CD34+ stem/progenitor cells serve as a significant reservoir of virus in HIV-infected individuals. Our data indicate that infection of bone marrow stem/progenitor cells with HIV occurs rarely, if ever, in vivo. In the present study, CD34+ cells were immunomagnetically purified from the bone marrow of HIV-seropositive individuals, and purified cells or colony-forming cells of the granulocyte/macrophage lineage were analyzed for HIV proviral DNA by the polymerase chain reaction. No HIV DNA was detected in colony-forming cells of the granulocyte/macrophage lineage from HIV-positive patients. Furthermore, no virus was found in CD34(+)-enriched cells from six of seven samples from asymptomatic HIV-infected individuals and four of four samples from patients with AIDS-related complex or AIDS. Thus, infected stem cells are not a major source of persistent HIV and do not account for hematopoietic suppression. These findings have positive implications for the concept of marrow reconstitution with autologous stem cells, genetically engineered for HIV resistance, following marrow-ablative antiviral therapy.

DNA, Viral↗

Effect of drug and diet treatment of mild hypertension on diastolic blood pressure. The TAIM Research Group.

The Trial of Antihypertensive Interventions and Management is a multicenter randomized trial designed to examine the diastolic blood pressure response of various combinations of pharmacological and dietary interventions in the treatment of mild hypertension (diastolic blood pressure 90-100 mm Hg). Eight hundred and seventy-eight participants at 110-160% of ideal weight were randomly allocated to nine drug/diet treatment groups receiving either a placebo, chlorthalidone (25 mg), or atenolol (50 mg), combined with a usual, a weight loss, or a low sodium/high potassium diet. The primary outcome was diastolic blood pressure change from baseline to 6 months. Seven hundred and eighty-seven participants had follow-up data. The mean baseline diastolic blood pressure was 93.8 mm Hg; 55.9% of the participants were male, and the weight loss diet group lost an average of 4.7 kg. Multiple comparisons were accounted for in the analysis. A significantly greater lowering of diastolic blood pressure (12.4 mm Hg) was achieved in the atenolol group compared with either the low sodium/high potassium diet group (7.9 mm Hg, p = 0.001) or weight loss group (8.8 mm Hg, p = 0.006). Adding weight loss to chlorthalidone significantly enhanced blood pressure lowering (15.1 mm Hg) when compared with the diuretic alone (10.8 mm Hg, p = 0.002), but adding a low sodium/high potassium diet (12.2 mm Hg, p = 0.029) did not. In the short-term treatment of mild hypertension where diastolic blood pressure is the sole consideration, drugs outperform diet, and weight loss is beneficial, especially with diuretics.

Adrenergic beta-Antagonists↗