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Biomedical subjects

R Fletcher

Publications and source records attributed to R Fletcher.

At least 55 records · Page 3Linked to original sources

Mild systolic dysfunction in heart failure (left ventricular ejection fraction >35%): baseline characteristics, prognosis and response to therapy in the Vasodilator in Heart Failure Trials (V-HeFT)

OBJECTIVES: This analysis sought to evaluate the clinical characteristics and outcome in heart failure with mild systolic dysfunction. BACKGROUND: Although heart failure with mild systolic dysfunction occurs commonly, this is an understudied area because clinical trials have usually excluded patients with ejection fraction >35%. METHODS: The 422 patients with left ventricular ejection fraction </=35% were compared with 172 with a left ventricular ejection fraction >35% in the Vasodilator in Heart Failure Trial (V-HeFT I), whereas in V-HeFT-II 554 patients with a left ventricular ejection fraction </=35% were compared with 218 patients with a left ventricular ejection fraction >35% for mortality and clinical care. For a left ventricular ejection fraction >35%, treatment with hydralazine/isosorbide dinitrate was compared with prazosin and placebo therapy in V-HeFT I, and hydralazine/isosorbide dinitrate was compared with enalapril in V-HeFT II for mortality, clinical course and change in physiologic variables: ejection fraction, plasma norepinephrine levels, ventricular tachycardia and echocardiographic variables. RESULTS: In both studies, patients with a left ventricular ejection fraction >35% differed principally in hypertensive history, higher functional capacity and radiographic and echocardiographic cardiac dimension from patients with a left ventricular ejection fraction </=35%, and plasma norepinephrine levels differed in V-HeFT II (p < 0.01). Patients with a left ventricular ejection fraction >35% had a lower cumulative mortality than those with a left ventricular ejection fraction </=35% (p < 0.0001) and less frequent hospital admissions for heart failure (p < 0.014, V-HeFT I; p < 0.005, V-HeFT II). Although cumulative mortality and morbidity did not differ between treatment groups in V-HeFT I, enalapril decreased overall mortality versus hydralazine/isosorbide dinitrate (p < 0.035) in V-HeFT II. For physiologic variables in V-HeFT II, enalapril decreased ventricular tachycardia at follow-up (p < 0.05). CONCLUSIONS: In V-HeFT, heart failure with mild systolic dysfunction was associated with different characteristics and a more favorable prognosis than heart failure with more severe systolic dysfunction. Enalapril decreased overall mortality and sudden death compared with hydralazine/isosorbide dinitrate. Prospective trials are needed to address therapy for heart failure with mild systolic dysfunction.

Aged↗

Nutrient intakes and impact of fortified breakfast cereals in schoolchildren.

OBJECTIVE: To report micronutrient intakes in Northern Ireland schoolchildren, and to establish the contribution of fortified breakfast cereal to overall nutrient intakes and achievement of current dietary recommendations. DESIGN: Analysis of dietary intakes and physical characteristics of participants in a randomly selected 2% population sample of 1015 schoolchildren aged 12 and 15 years in Northern Ireland during the 1990/1 school year. MAIN OUTCOME MEASURES: Dietary intakes, physical characteristics, and their association with consumption of fortified breakfast cereal. RESULTS: Mean micronutrient intakes were generally adequate with the exception of low intakes of folate (boys and girls) and iron (girls). Fortified breakfast cereals, consumed by a high proportion (94% boys; 83% girls) of the sample, were associated with higher daily intakes of most micronutrients and fibre and with a macronutrient profile consistent with current nutritional recommendations. Appreciable proportions of subjects who did not consume fortified breakfast cereals had daily intakes that fell below the lower reference nutrient intake for riboflavin, niacin, folate, vitamin B-12, and iron (girls). CONCLUSIONS: The results demonstrate the potential of fortification in contributing to micronutrient intakes of schoolchildren, particularly where requirements are high, or for those on marginal diets of low nutritional quality.

Adolescent↗

Neurocristopathy resembling neurofibromatosis type 1 in an NGF-SV40 transgenic line.

BACKGROUND: Animal models of carcinogenesis have been produced in transgenic mice by directing the expression of oncogenes such as SV40 T antigen and myc to different tissues by creating fusions with promoter/enhancer elements of various mammalian or viral genes. RESULTS: A transgenic mouse line was created in which SV40 T antigen is under the control of the mouse nerve growth factor (NGF) promoter. While the oncogene is expressed in a wide range of NGF producing tissues, it specifically causes the development of either neurofibromas or neurofibrosarcomas similar to those found in the human disease neurofibromatosis type 1 (NF1). These tumours are completely penetrant and appear after a mean latency of about 8 months. In contrast to the previously reported neurofibromatosis mouse model HTLV-1 tax, the tumours in these transgenic mice arise in Schwann cells rather than perineural fibroblasts and have a very restricted tissue distribution. In a cell line cloned from a neurofibroma from these mice, NGF was detected in the culture medium at levels similar to those produced by cultured primary Schwann cells. CONCLUSION: As all animal model for a heritable neurocristopathy resembling NF1, this mouse should allow study of the pathology and treatment of this disease.

Animals↗

Intra-oral comparison and evaluation of the ability of fluoride dentifrices to promote the remineralization of caries-like lesions in dentin and enamel.

The effect of three types of fluoride dentifrices and one non-fluoride dentifrice were evaluated and compared intra-orally for their ability to promote the remineralization of caries-like lesions in thin sections of human dentin and enamel. The three fluoride dentifrices were silica based. One dentifrice contained 0.76% sodium monofluorophosphate (MFP), another contained 0.247% sodium fluoride (NaF), and the third contained 0.247% NaF plus 1.3% pyrophosphate and 1.5% polyvinylmethyl ether/maleic acid (PVM/MA) copolymer (denoted NaF/PPi). The fourth dentifrice (placebo) was also silica based, but contained no fluoride, and served as a negative control. Two week treatment resulted in the following percent mineral changes for the enamel specimens: +21 +/- 16 for MFP, +10 +/- 30 for NaF, +16 +/- 15 for NaF/PPi, and -30 +/- 30 for the placebo. The respective percent mineral change values for the dentin specimens were +28 +/- 20 for MFP, +22 +/- 19 for NaF, +28 +/- 18 for NaF/PPi, and -34 +O/- 61 for the placebo. A statistical analysis revealed that the three fluoride dentifrices were significantly better (p<0.05) than the placebo at promoting remineralization for both types of specimens. No significant differences were found among the three fluoride dentifrices. The following can be concluded from this study: 1) silica based dentifrices containing MFP and NaF are effective at remineralizing caries-like lesions in both enamel and dentin; 2) there was no statistical difference between NaF and MFP in their ability to promote remineralization; and 3) pyrophosphate does not interfere with the remineralizing effects of NaF.

Analysis of Variance↗

How do physicians talk with their patients about risks?

To describe the communication about risk between community-based physicians and their patients, the authors audiotaped 160 physician-patient encounters in the private practices of 19 physicians. Coding was done using a structured scheme to identify the presence of talk about risk of future illness, and to describe its characteristics. Patient understanding and satisfaction were assessed through an interview. Risk discussion occurred in 26% (95% CI 19%-33%) of the visits, quantitatively in two cases and specifically with respect to outcome in 48% (95% CI 40%-56%) of the visits. The patients initiated only 16% of this discussion but were, in general, satisfied with their care and the information they had received, but they had poor recall of the specifics of the discussion.

Communication↗

Raised end-expiratory alveolar pressures during cardiac surgery.

Increased end-expiratory pressure (EEP) is usually associated with expiratory obstruction. By pressing the "expiratory pause hold" button on the Servo ventilator 900C, EEP was measured at four stages during coronary bypass surgery: before sternotomy (I), after sternotomy with the sternal edges fully retracted (II), after completed extracorporeal circulation, sternal edges still retracted (III) and after sternal closure (IV). Five patients had EEP values > 3 cm H2O at stage I. EEP decreased after opening the sternum and was still low after extracorporeal circulation (stages II and III). However, sternal closure was associated with large increases in EEP (maximum value 22 cm H2O). Typically, patients in whom EEP exceeded 5 cm H2O at stage IV also had raised values at stage I. These patients had obstructive preoperative spirometry patterns and tended to be of shorter stature in relation to weight than patients in whom EEP did not exceed 5 cm H2O. The changes in EEP are believed to be caused by changes in lung volume as a result of opening and closing the sternum and by increased lung water after extracorporeal circulation.

Aged↗

Psychophysical visual function, retinopathy, and glycemic control in insulin-dependent diabetics with normal visual acuity.

We studied relations between psychophysical visual function and grade of retinopathy, glycemic control and clinical background data in 51 insulin-dependent diabetic patients, aged 17-47 years. Three separate qualities of visual function were examined, macular recovery time (nyctometry; 2 min adaptation), contrast sensitivity (Vistech 6000 chart; between 1.5 and 18 cycles per degree (cpd)) and colour vision (Fletcher DS8; protan/deutan and tritan). Only contrast sensitivity of 6 cpd was associated with the grade of retinopathy; reduced function was found in patients with retinopathy compared to those without. No correlations between macular recovery, contrast sensitivity and colour vision were found. None of the visual functions was significantly related to glycemic control, age, duration of diabetes, blood pressure, intraocular pressure, or urinary albumin excretion. Our data suggests that the neurosensory function of contrast sensitivity correlates more sensitively to the grade of diabetic retinopathy than macular recovery and colour vision. Cross-sectional assessments of different psychophysical visual functions seem to be of restricted clinical value as indicators of preceding glycemic control in diabetic patients with no or mild nonproliferative retinopathy.

Adolescent↗

Ejection fraction, peak exercise oxygen consumption, cardiothoracic ratio, ventricular arrhythmias, and plasma norepinephrine as determinants of prognosis in heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Recognition of the complex pathophysiology of heart failure and its high mortality has emphasized the need for prognostic markers that can be used in clinical assessment as well as in the design of mortality trials. Data from the Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials (V-HeFT I, 642 patients; V-HeFT II, 804 patients) were therefore examined to determine the influence of prerandomization measurements on subsequent mortality. METHODS AND RESULTS: Patients entered into these trials were men with cardiac dysfunction and reduced peak exercise capacity. Measurements included in this analysis were left ventricular ejection fraction (EF) measured by radionuclide angiography, peak bicycle exercise oxygen consumption (VO2), cardiothoracic ratio (CTR) measured on a chest x-ray, ventricular arrhythmias assessed in a core laboratory by short-term Holter monitoring, plasma norepinephrine and plasma renin activity measured in a core laboratory only in V-HeFT II, and a variety of diagnostic and demographic data. The variables related only weakly to each other. EF, VO2, and CTR were powerful independent predictors of all-cause mortality in both studies. Ventricular arrhythmia was a significant independent predictor in V-HeFT II but not in V-HeFT I. Plasma norepinephrine but not plasma renin activity measured in V-HeFT II also had independent prognostic value. Other variables did not exert an independent effect on mortality. CONCLUSIONS: Optimal assessment of the mortality risk in an individual or a group of individuals with heart failure uses measurement of EF, peak VO2, CTR, plasma norepinephrine, and the presence of ventricular arrhythmias.

Arrhythmias, Cardiac↗