Search PubMedSearch

Biomedical subjects

L Farrell

Publications and source records attributed to L Farrell.

31 records · Page 2Linked to original sources

The influence of atrial fibrillation on prognosis in mild to moderate heart failure. The V-HeFT Studies. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Atrial fibrillation occurs commonly in heart failure; however, its importance in terms of prognosis is controversial. METHODS AND RESULTS: We assessed the relation of atrial fibrillation on first Holter monitor to morbidity and mortality in mild to moderate heart failure in 632 patients in the Veterans Affairs Vasodilator-Heart Failure Trial (V-HeFT) I and 795 patients in V-HeFT II: Ninety-nine patients in atrial fibrillation and 533 patients in sinus rhythm were followed for a mean of 2.5 years (range, 6 months to 5.7 years) in V-HeFT I; 107 patients in atrial fibrillation and 688 patients in sinus rhythm in V-HeFT II were followed for a mean of 2.5 years (range, 6 months to 5.0 years). V-HeFT I compared treatment with prazosin, hydralazine-isosorbide dinitrate, and placebo, whereas V-HeFT II compared hydralazine-isosorbide dinitrate with enalapril. Follow-up evaluations included serial Holter monitors, serial metabolic exercise testing, hospitalization data, and clinical examinations. In V-HeFT I, cumulative mortality at 2 years was 0.34 for patients with atrial fibrillation and 0.30 for patients in sinus rhythm (p = 0.25). Overall cumulative mortality was 0.54 for atrial fibrillation patients and 0.64 for sinus rhythm patients (p = 0.86). In V-HeFT II, cumulative mortality at 2 years was 0.20 for patients with atrial fibrillation and 0.21 for patients with sinus rhythm (p = 0.68), and overall cumulative mortality was 0.46 for atrial fibrillation patients and 0.52 for those in sinus rhythm (p < 0.46). Sudden death was not increased with atrial fibrillation in V-HeFT I patients (p = 0.64) or in V-HeFT II (p = 0.68). By multivariate analysis, the relative mortality risk for atrial fibrillation was 0.95 in V-HeFT I and 0.76 in V-HeFT II: Metabolic exercise testing, showed no significant difference in mean change in peak oxygen consumption between patients with atrial fibrillation and those with sinus rhythm in V-HeFT I and a slight decrease late in V-HeFT II: Hospitalization rate for heart failure was not increased in either study. The embolic event rate was not increased for atrial fibrillation patients: 3% versus 4.9% of patients in sinus rhythm (p = 0.41) in V-HeFT I and 4.0% versus 6.0% in V-HeFT II patients (p = 0.44). A secondary analysis compared mortality of patients in atrial fibrillation with that of patients in sinus rhythm on all Holters: Mortality was not increased overall (p = 0.72 in V-HeFT I and p = 0.35 in V-HeFT II). CONCLUSIONS: Atrial fibrillation does not increase major morbidity or mortality in mild to moderate heart failure.

Atrial Fibrillation

Evaluation by patients with heart failure of the effects of enalapril compared with hydralazine plus isosorbide dinitrate on quality of life. V-HeFT II. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Two new questionnaires concerning the quality of life of patients with heart failure were used in a randomized, controlled trial to determine if the patients' perceptions of the effects of enalapril on their daily activities and sense of well-being were different from those of a group treated with hydralazine and isosorbide dinitrate. METHODS AND RESULTS: The questionnaires were completed at baseline and at 3 months, 6 months, and subsequently every 6 months during follow-up, which averaged 2.5 years (range, 0.5-5.7 years). Data from the questionnaires were reliable as indicated by correlation coefficients between repeated baseline scores of 0.88 and 0.87. Both treatment groups showed a progressive deterioration in quality of life as measured by both questionnaires. The questionnaire scores of the two treatment groups were not significantly different at any follow-up visit. Furthermore, there were no differences between treatments among subgroups defined by baseline questionnaire scores, peak oxygen consumption, ejection fraction, previous vasodilator use, and plasma norepinephrine concentration. CONCLUSIONS: Although several factors may limit the generalization of these results, the lack of a difference with regard to patients' quality of life is an important consideration for the evaluation of the relative therapeutic efficacy of these vasodilators.

Attitude to Health

Incidence of thromboembolic events in congestive heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: The incidence of thromboembolism and the benefit of anticoagulation in congestive heart failure are controversial. METHODS AND RESULTS: The data base provided by the Veterans Affairs Vasodilator-Heart Failure Trials (V-HeFT I and II) was examined retrospectively to address these issues. In V-HeFT I, 642 men with heart failure were followed an average of 2.28 years, providing 1,464 patient-years of follow-up. In V-HeFT II, 804 men were followed an average of 2.56 years, with 2,061 patient-years of follow-up. Mean left ventricular ejection fraction was 30% in V-HeFT I and 29% in V-HeFT II: Functional capacity was at the interface of classes II and III with a peak exercise oxygen consumption of 14.7 mL.kg-1 x min-1 in V-HeFT I and 13.7 mL.kg-1 x min-1 in V-HeFT II: Warfarin and antiplatelet agents were administered at the discretion of individual investigators. The incidence of all thromboembolic events during 1,068 patient-years without warfarin in V-HeFT I was 2.7/100 patient-years and during 1,188 patient-years in V-HeFT II was 2.1/100 patient-years and was not reduced in patients treated with warfarin. Patients experiencing events had a lower peak exercise oxygen consumption (p < 0.03 in V-HeFT I and p < 0.001 in V-HeFT II) and a lower mean ejection fraction (p = 0.10 in V-HeFT I and p = 0.07 in V-HeFT II). Atrial fibrillation was not associated with an increased risk of thromboembolic events. CONCLUSIONS: The incidence of thromboembolism and stroke in class II or III congestive heart failure is not high and may not be significantly reduced with warfarin treatment. Routine use of anticoagulants in patients with heart failure may not be justified.

Cerebrovascular Disorders

Effects of intravenous infusions of diaspirin cross-linked hemoglobin (DCLHb) on sheep.

The purpose of this study was to compare the cardiopulmonary, hematologic, and immunologic responses of unanesthetized sheep to single, "topload", intravenous infusions of either 10 mL/Kg or 40 mL/Kg of Diaspirin Cross-Linked Hemoglobin, 10 mL/Kg or 40 mL/Kg of a Human Serum Albumin (HSA) solution oncotically adjusted with human serum albumin to approximately match the oncotic pressure of the DCLHb, or 10 mL/Kg of Erythrocyte Hemolysate solution prepared in a manner similar to that commonly described in the literature and referred to as "stroma free hemoglobin". Solutions were infused at a rate of 1 mL/Kg/minute and animals were monitored for 72 hours after infusion. These studies demonstrated that in sheep infusion of either DCLHb or HSA solutions was well tolerated and did not produce a significant increase in plasma C3a levels, an increase in the plasma concentration of thromboxane B2, or unexpected fluid shifts. In contrast, infusion of the Erythrocyte Hemolysate produced a greater than 10-fold increase in plasma C3a concentrations, a greater than 6000-fold increase in plasma TxB2 concentration, significant fluid shifts, and changes in a variety of other parameters consistent with induction of a dramatic inflammatory response. These results indicate that appropriately prepared and purified DCLHb solutions do not elicit an inflammatory reaction in sheep.

Animals

Isolation, characterization, and in vitro expression of a cDNA that encodes the kidney isoenzyme of the mitochondrial glutaminase.

A cDNA that encodes the kidney isoenzyme of the mitochondrial glutaminase (pGA) was generated by recombination of two cDNAs that were isolated from a random-primed rat brain lambda gt11 library. pGA encodes 674 amino acids which includes an N-terminal sequence of 16 residues that should form an amphipathic helix, typical of a mitochondrial targeting sequence. Residues 73-90 correspond to the N-terminal sequence of the more abundant 65-kDa glutaminase peptide. In vitro transcription and translation of pGA yields a 72-kDa peptide that is immunoprecipitated with glutaminase-specific antibodies. Incubation of the glutaminase precursor with isolated mitochondria yields the 68- and 65-kDa peptides that are characteristic of the mature glutaminase. Thus, the two mature glutaminase peptides are synthesized from a single precursor. The complete 3' nontranslated region of the GA mRNA was characterized by sequencing a GA cDNA (pGA12) that was isolated from an oligo(dT)-primed rat kidney lambda gt10 library. This segment contains numerous AU-rich regions, four potential stem-loop structures, and a 48 base pair repeat of CA dinucleotides. Such domains may contribute to the increased stability of the GA mRNA that occurs in response to metabolic acidosis.

Amino Acid Sequence

Lithium and neuromuscular transmission.

The actions of lithium on end-plate depolarization and on indirect and direct twitch response of isolated guinea pig muscle were investigated. At clinical concentrations lithium did not cause depolarization, nor did it affect the depolarizing action of carbachol. Lithium also had no effect on the twitch response to nerve stimulation throughout its therapeutic serum concentration range and it did not alter the ED50 of pancuronium. When animals were chronically pretreated with lithium there appeared to be a slight reduction in dosage requirement for d-tubocurarine. At concentrations well above therapeutic serum levels, end-plate depolarization as well as indirect and direct twitch responses were depressed. It is concluded that, at therapeutic levels, there is minimal interaction of lithium with competitive neuromuscular blocking agents.

Animals

Temperature and potency of d-tubocurarine and pancuronium in vitro.

The concentrations of d-tubocurarine and pancuronium producing 50% block of the indirectly elicited twitch were determined in isolated mouse nerve-diaphragm preparations at 37 and 25 C. The contralateral side was used as a control in a 2 x 2 factorial analysis of variance. Cooling shifted the dose-response curves for both drugs to the left, but only slightly (from 1.69 +/- 0.022 microM to 1.49 +/- 0.021 microM with d-tubocurarine and from 0.65 +/- 0.012 microM to 0.46 +/- 0.009 microM with pancuronium). The dose-response relationship was, however, so steep (Hill coefficient approximately 5 to 6) that a slight horizontal shift of the dose-response curve corresponds to a considerable decrease in the twitch response at a concentration midway between the curves. Thus, studies using only the concentration that produces partial block of twitch responses misleadingly suggest a large effect of temperature. Similarly, if in another system the curve were to shift to the right even only slightly, a temperature effect in the reverse direction might be reported. It is concluded that temperature appears to have little influence on cellular potency of neuromuscular blocking agents.

Animals

Infectious disease patterns in the Waorani, an isolated Amerindian population.

The Waorani Indians of eastern Ecuador provide a unique opportunity for studying exposure of an isolated human population to various infectious disease agents. Using serologic tests to determine antibody prevalence, skin test data, and stool examination for parasites, we have been able to construct a profile of infectious diseases which are endemic, and others which have been introduced into the Waorani population. These findings are compared with similar data reported from elsewhere in the Amazon. Serologic studies demonstrating the presence of antibody to measles and poliovirus type 3 after vaccination indicate that the Waorani respond normally to viral challenge with these agents. The question of genetic inability among aboriginal Amerindians to respond to viral agents is discussed. Finally, general recommendations are made regarding the future health care of the Waorani.

Adolescent

Phleomycin-stimulated degradation of deoxyribonucleic acid in Escherichia coli.

Phleomycin stimulates the degradation of DNA by energy-dependent endonuclease and exonuclease reactions in Escherichia coli rec(+) cells and in recB(-) and recC(-) cells that lack an adenosine triphosphate-dependent nuclease functioning in the repair of ultraviolet (UV) lesions. Exonuclease activity is blocked in T4 phage-infected cells. The endonuclease reaction produces 10(7)-dalton segments resembling those produced in colicin E2-treated cells. These differ from the random-sized segments produced in UV-irradiated cells, or the 10(6)-dalton segments made in T4 phage-infected cells. A mutant selected for phleomycin tolerance is cross-tolerant to colicin E2, and some mutants selected for colicin E2 tolerance are cross-tolerant to phleomycin. On the basis of these cross-tolerances and the similarities between the effects of phleomycin and E2-stimulated nucleases, the suggestion is made that both agents may stimulate the same nuclease reactions in E. coli cells.

Antibiotics, Antineoplastic

Nutrition information sources.

Medical personnel and medical librarians may tend to think of nutrition in medical terms and to forget its interdisciplinary aspects. For this reason, it is desirable for medical librarians to become familiar with a variety of sources of information on the composition of foods, nutrient values, food additives, and food protection. Many of these are government publications from such agencies as the U.S. Department of Agriculture, the National Research Council, and the Food and Agriculture Organization. Less familiar sources include nutrition materials from state agricultural experiment stations and extension services and important data published in a wide range of scientific or agricultural journals, which may be located through Nutrition Abstracts and Reviews, Food Science and Technology Abstracts, and the Bibliography of Agriculture. Sources of current information on nutrition research in progress include the Department of Agriculture's Current Research Information System (CRIS) and selective listings from the Smith-sonian Information Exchange.

Abstracting and Indexing

Lust.

Explore the source record for details and available documents.

Attitude