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H L Greene

Publications and source records attributed to H L Greene.

At least 19 recordsLinked to original sources

A study of the cardiac effects of bromochlorodifluoromethane (halon 1211) exposure during exercise.

Bromochlorodifluoromethane (halon 1211, a fire extinguisher), like other fluorocarbons, has been linked with ventricular arrhythmias and myocardial depression. Ten healthy firefighters, aged 40-50, were exposed to 1,000 ppm halon while exercising, in a double-blind, placebo-controlled crossover experiment, and were monitored during and after exposure. Complex ectopy (ventricular couplets and idioventricular rhythm) occurred in two subjects with halon, but none with placebo. One subject had 49.5 ventricular premature beats (VPB)/hour during the period of halon exposure and subsequent 8 hours and only 8.7 VPB/hour during the same period of placebo. In addition, 8 of the 10 subjects had a smaller systolic blood pressure rise during exercise with halon than with placebo. None of the observed differences was statistically significant. These results are consistent with findings in other investigations, suggesting that occupational fluorocarbon exposures may be cardiotoxic in certain individuals, although the small sample sizes used in this and other studies have resulted in limited statistical power to demonstrate this effect.

Adult

Pattern generator system as a versatile visual stimulator.

We have designed and implemented a Motorola 68000 microprocessor-based pattern generator system (PGS) that uses a color video display terminal (VDT) to provide light stimuli to the intact vertebrate retina. This communication is intended for those who are considering acquisition of a commercial retinal stimulator or those who are custom designing their own pattern generator system. The discussion surveys the features to be included as well as design factors which must be considered in such a device. The memory organization of the PGS allows as stimuli multiple, complex patterns consisting of one or more disks, annuli, bars or gratings to flash or modulate in intensity according to a pre-defined function. In addition, patterns can move smoothly in any direction at selectable, uniform speeds without the re-drawing of video memory. The presence of a 12-bit A/D converter internal to the PGS allows a dynamic change in stimulus position, speed or pattern based upon physiological feedback. A physically realistic image size (0.9 cm2) and resolution (20 mu/pixel) in the retinal plane are achieved with simple intervening optics. The video field rate of 60 Hz is above the flicker fusion frequency for most vertebrate animals and does not induce artifacts in cellular responses. The PGS operating in a PC-based environment meets the requirements of a versatile optical stimulator for investigations in retinal electrophysiology.

Ambystoma

The Cardiac Arrhythmia Suppression Trial: first CAST ... then CAST-II.

The Cardiac Arrhythmia Suppression Trial (CAST) was a study designed to test the hypothesis that suppression of ventricular premature complexes after a myocardial infarction would improve survival. Preliminary results showed that suppression of ventricular premature complexes with encainide and flecainide worsened survival, and the CAST continued as the CAST-II with moricizine compared with its placebo. The protocol for the CAST-II was changed to attempt to enroll patients more likely to experience serious arrhythmias. The enrollment time was narrowed to 4 to 90 days after myocardial infarction; the qualifying ejection fraction was lowered to less than or equal to 0.40; a higher dose of moricizine could be used; early titration itself was double-blind with a placebo, and the definition of disqualifying ventricular tachycardia was changed to allow patients with more serious arrhythmias to be entered into the trial. The Cardiac Arrhythmia Suppression Trial-II was subsequently terminated prematurely because 1) patients treated with moricizine had an excessive cardiac mortality rate during the 1st 2 weeks of exposure to the drug, and 2) there appeared to be little chance of showing a long-term survival benefit from treatment with moricizine. This report outlines the rationale behind the Cardiac Arrhythmia Suppression Trial and the reasons for selection of the drugs used in the CAST and CAST-II.

Anti-Arrhythmia Agents

Plasma lipids and lipoproteins during 6 d of maintenance feeding with long-chain, medium-chain, and mixed-chain triglycerides.

This study assessed fasting plasma lipids and lipoproteins and postprandial plasma lipids in healthy male subjects fed liquid-formula diets containing 40% of total energy as long-chain (LCT, primarily C18:1 and C18:2), medium-chain (MCT, C8:0-C10:0), or mixed-chain (structured lipid, STL, mostly C8:0, C10:0, and C22:0) triglycerides for 6 d. None of the diets altered plasma cholesterol concentrations. HDL cholesterol was decreased 14% by the STL diet (P < 0.044) and 15% by the MCT diet (P < 0.004) but was unchanged by the LCT diet. Plasma triglycerides were elevated 42% by the MCT diet (P < 0.006), but were unaltered by either the STL or LCT diets. Neither the STL nor the MCT diets produced changes in fasting lipoprotein lipid composition; however, during the LCT diet, VLDLs became enriched in triglyceride and LDLs became enriched in cholesterol. Postprandial triglyceridemia was significantly greater after subjects consumed the LCT diet than it was after they consumed either the STL or MCT diets, which were similar. Short-term feeding of MCT and STL diets produces significant changes in lipid metabolism. An understanding of the long-term effects of these diets awaits further study.

Adult

Vitamin update.

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Anorexia

Clinical significance and management of arrhythmias in the heart failure patient.

Congestive heart failure (CHF) is a common manifestation of hypertension, coronary artery disease, and dilated cardiomyopathy. The Framingham study showed that the incidence of CHF increases twofold with each decade of age. The presence of CHF increases the age-adjusted death rate 5.5-fold for women and 8-fold for men, and it increases the sudden death rate 5.5-fold in both men and women. Ventricular arrhythmias are a common accompaniment of CHF. Ambient ventricular premature complexes occur in most of these patients, and nearly one half of all CHF patients will have nonsustained ventricular tachycardia on a 24-h ambulatory electrocardiographic (Holter) recording. In addition, low left ventricular ejection fraction (LVEF) predicts inducible sustained ventricular tachycardia on electrophysiologic study. One-year mortality increases with worsening New York Heart Association (NYHA) Functional Class and decreasing LVEF. As the overall yearly mortality increases, the proportion of patients who die of arrhythmias decreases. The precise mechanism of death is frequently difficult to assess. Nonarrhythmic causes of death include CHF, shock, electromechanical dissociation, and myocardial rupture. Arrhythmic causes are most commonly due to ventricular tachycardia/ventricular fibrillation. Bradycardic events (asystole or heart block) are usually associated with progressively worsening CHF. Noncardiac causes that may confuse classification include pulmonary embolus and cerebrovascular accident. Because many patients have ischemic heart disease as the etiology of the CHF, a recurrent ischemic event can likewise make classification difficult. Overall, approximately one half of all deaths in CHF are arrhythmic and one half are nonarrhythmic.

Adult

Retinol (vitamin A) and riboflavin (vitamin B2) administration and metabolism in very low birth weight infants.

The combination of marginal hepatic retinol stores at delivery and the reduction of daily retinol dose due to complications with the delivery system places the VLBW infant receiving parenteral nutrition at high risk for retinol deficiency during the first month of life. This has serious health implications because retinol is essential during this period for normal growth and repair of the pulmonary tissue in VLBW infants. Enterally fed VLBW infants, on the other hand, receive relatively higher doses of retinol from vitamin-supplemented premature infant formula and fortified breast milk. Equally serious is the problem of monitoring vitamin A status in infants receiving supplemental doses of vitamin A. It seems clear that while plasma vitamin A levels are the most easily available method of monitoring vitamin A status, further studies are necessary to determine if these levels correlate with hepatic content. This is of particular concern since liver disease is common in VLBW infants and vitamin A hepatotoxicity has been described in a cohort of 41 patients receiving therapeutic doses of the vitamin. While further research of daily enteral and parenteral retinol requirements of VLBW infants should continue, formulation of a specific VLBW parenteral vitamin supplement should also be developed.

Delivery, Obstetric

Late outcome of survivors of out-of-hospital cardiac arrest with left ventricular ejection fractions greater than or equal to 50% and without significant coronary arterial narrowing.

In a retrospective survey of 1,195 survivors of out-of-hospital ventricular fibrillation, 43 patients were identified in whom left ventricular ejection fraction was greater than or equal to 0.50 and in whom no coronary artery stenosis of greater than or equal to 50% luminal diameter were present. Thirteen (30%) of these patients had hypokinesia on left ventriculography, and 20 patients (47%) had a persistently abnormal electrocardiogram. Seven patients (16%) had recurrent out-of-hospital cardiac arrest during an average follow-up of 86 +/- 54 months. The presence of either wall motion or electrocardiographic abnormalities defined patients with a several-fold higher risk of recurrent cardiac arrest than those without such abnormalities. The risk for recurrent cardiac arrest within 5 years was 30% in those with abnormal electrocardiograms versus 5% in the others (p less than 0.03). Age was an independent predictor of recurrent cardiac arrest in this group (p less than 0.01); surprisingly, recurrent cardiac arrest was occurring more often among younger patients. Although cardiac arrest is unusual in patients without major structural heart disease, its recurrence in such survivors is common. Patients at relatively high risk for recurrent ventricular fibrillation can be identified by their youth and by abnormalities detected on the surface 12-lead electrocardiogram or by contrast left ventriculography.

Adult

Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial.

BACKGROUND AND METHODS: In the Cardiac Arrhythmia Suppression Trial, designed to test the hypothesis that suppression of ventricular ectopy after a myocardial infarction reduces the incidence of sudden death, patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The use of encainide and flecainide was discontinued because of excess mortality. We examined the mortality and morbidity after randomization to encainide or flecainide or their respective placebo. RESULTS: Of 1498 patients, 857 were assigned to receive encainide or its placebo (432 to active drug and 425 to placebo) and 641 were assigned to receive flecainide or its placebo (323 to active drug and 318 to placebo). After a mean follow-up of 10 months, 89 patients had died: 59 of arrhythmia (43 receiving drug vs. 16 receiving placebo; P = 0.0004), 22 of nonarrhythmic cardiac causes (17 receiving drug vs. 5 receiving placebo; P = 0.01), and 8 of noncardiac causes (3 receiving drug vs. 5 receiving placebo). Almost all cardiac deaths not due to arrhythmia were attributed to acute myocardial infarction with shock (11 patients receiving drug and 3 receiving placebo) or to chronic congestive heart failure (4 receiving drug and 2 receiving placebo). There were no differences between the patients receiving active drug and those receiving placebo in the incidence of nonlethal disqualifying ventricular tachycardia, proarrhythmia, syncope, need for a permanent pacemaker, congestive heart failure, recurrent myocardial infarction, angina, or need for coronary-artery bypass grafting or angioplasty. CONCLUSIONS: There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infarction in patients treated with encainide or flecainide. Nonlethal events, however, were equally distributed between the active-drug and placebo groups. The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown.

Actuarial Analysis

The healthy responder phenomenon in non-randomized clinical trials. CAST Investigators.

An example from the Cardiac Arrhythmia Suppression Trial (CAST) illustrates what we term the 'healthy responder' phenomenon. The hypothesis is that patients who respond to a given treatment are healthier than patients who do not respond. In observational studies this results in an apparent but not real benefit for the treatment. The unique design of CAST, namely, titration before randomization, allows illustration of this phenomenon since we can view the study as both a non-randomized as well as a randomized trial of therapy. We conclude that, in demonstration of a drug effect, randomized trials are essential.

Arrhythmias, Cardiac

Analysis of aldehydic lipid peroxidation products by TLC/densitometry.

We have explored the use of thin-layer chromatography (TLC)/densitometry in both the reflectance and fluorescence mode for quantitation of specific products of lipid peroxidation. Aldehydic peroxidation products were generated by exposure of arachidonic acid to iron and ascorbic acid for 24 hr. Several methods for the quantitative analysis of peroxidation products by TLC/densitometry were compared using two different aldehyde-specific derivatizing reagents, namely dinitrophenylhydrazine (DNPH) and cyclohexanedione (CHD). DNPH hydrazones of the arachidonic acid-peroxidation products, upon TLC separation on silica gel, revealed prominent alkanal and hydroxyalkenal bands. Reverse phase high performance liquid chromatography confirmed that the primary alkanal component was hexanal, while the primary hydroxyalkenal was 4-hydroxynoneal. Semiquantitative methods for the direct analysis of these products by TLC/densitometry were worked out based on the use of external hydrazone standards. TLC/densitometry (fluorescence mode) was used to measure CHD adducts of aldehydes by forming the derivatives in the presence of decanal (used as an internal standard) and separating the derivatives by reverse phase TLC. Hexanal-CHD was detectable upon application of 0.5 nanomoles while 4-hydroxynoneal showed a lower response and was detectable with 10 nanomoles. Using appropriate response factors, hexanal and 4-hydroxynonenal were measured in the aldehyde sample from arachidonic acid and results were similar to those obtained by the DNPH method. Similar approaches were used to analyze the peroxidation products of docosahexaenoic acid (24-hr exposure) and of rat liver microsomes exposed to iron for 30 min. The DHA peroxidation products contained extremely low levels of alkanals, while polar aldehydes and hydroxyalkenals were prominent. Formation of alkanals, osa-zones, hydroxyalkenals and phospholipid aldehydes from iron-expoded microsomes was also demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehydes

Biphasic changes in phospholipid hydroperoxide levels during renal ischemia/reperfusion.

The involvement of lipid peroxidation in renal ischemia/reperfusion was explored by measuring changes in the cortical content of specific primary lipid hydroperoxides (using chemluminescent detection with HPLC) following ischemia and reperfusion and by correlating the changes in hydroperoxide content with measurements of renal blood flow. Phosphatidylcholine and phosphatidylethanolamine hydroperoxide concentrations were significantly lowered during 30 or 60 min of ischemia (to levels less than 50% of control at 60 min). Following 30 min of renal ischemia, reperfusion resulted in a rebound of phospholipid hydroperoxide tissue content to levels higher than controls. Increased phospholipid hydroperoxide formation was not, however, observed in response to reperfusion following long-term (60 min) ischemia. In separate animals it was demonstrated that following 30 min ischemia and reperfusion, renal blood flow recovers to about 65% of control in 1 h. In contrast, following 60 min ischemia and reperfusion, the renal blood flow remains more highly impaired (less than 25% recovery for periods up to 24 h). These results imply that phospholipid hydroperoxides are produced and accumulate in the kidneys under normal aerobic conditions and that lipid peroxidative activity increases during renal ischemia/reperfusion to an extent dependent on the degree of local blood perfusion.

Animals

Hyperlipidemia and fatty acid composition in patients treated for type IA glycogen storage disease.

Because glycogen storage disease type IA (GSD-IA) is characterized by recurrent episodes of hypoglycemia that promote a marked elevation in blood triglyceride levels, we evaluated plasma lipid levels in 12 patients with GSD-IA on a regular basis. Six of the 12 patients had plasma fatty acid composition measured; because of possible essential fatty acid deficiency, urinary prostaglandin excretion was also measured. All patients had triglyceride levels between 1440 and 6120 mg/dl (16.25 to 69.09 mmol/L) before treatment. After treatment to promote blood glucose levels of 75 to 85 mg/dl (4.2 to 4.7 mmol/L), triglyceride levels in each of 11 patients were between 189 +/- 31 (2.13 +/- 0.35 mmol/L) and 510 +/- 60 mg/dl (5.76 +/- 0.68 mmol/L). The lipoprotein fatty acid composition in six patients showed a substantial elevation in C16:0, C16:1 omega 7, and C18:1 omega 9, but no increase in C20:3 omega 9 (the fatty acid that characteristically increases in essential fatty acid deficiency). In addition, each of the six patients had normal 24-hour urinary excretion of prostaglandin. One patient, whose triglyceride levels remained elevated despite dietary treatment, was given either clofibrate, lovastatin, niacin, or fish oil. With the exception of lovastatin, these agents produced a decrease in triglyceride values for 1 to 2 months; however, by 3 months triglycerides reached pretreatment levels. Combined treatment with clofibrate and niacin resulted in a sustained decrease in plasma triglyceride levels for 4 months. The findings indicate that dietary management of GSD-IA is usually associated with improvements in triglyceride levels; however, patients maintain triglyceride values between 300 and 500 mg/dl (3.38 to 5.65 mmol/L). No patient had biochemical evidence of essential fatty acid deficiency.

Adolescent

Intravenous vitamins for very-low-birth-weight infants.

Term infants and children appear to adapt to large variations in vitamin intakes. This is supported by the finding of similar blood levels of vitamins despite several-fold differences in intake on a body weight basis. By contrast, the finding of marked elevation of some vitamins and low levels of others seen in very-low-birth-weight (VLBW) infants (less than 1500 g) suggest that this group has less adaptive capacity to high- or low-dose intakes. This indicates that their vitamin intakes need to be more closely aligned with actual needs. This paper reviews previously published data on vitamins A, E, B2, and B6 from VLBW infants receiving total parenteral nutrition (TPN). Vitamin A. VLBW infants are relatively deficient in retinol (R) at birth. During TPN large losses of R onto the delivery sets result in a further decline in stores of R as reflected in a progressive decline in plasma R during TPN. Because of the reported lower incidence of bronchopulmonary dysplasia associated with intramuscular vitamin A treatment, alternative methods of vitamin A delivery during TPN have been suggested. First, the vitamins were mixed with Intralipid (IL) and, second, retinyl palmitate (RP) rather than R was used. There was little in vitro loss of R when mixed with IL, and in vivo treatment resulted in higher blood levels after 1 month of retinol administration in IL than seen previously (21.4 +/- 4.2 vs 14.1 +/- 3.7 micrograms/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-Response Relationship, Drug

Nutrient balance in humans: effects of diet composition.

The purpose of this study was to examine the effect of alterations in diet composition on energy expenditure and nutrient balance in humans. Eight adults (three men, five women) ate a high-carbohydrate (60% of calories from carbohydrate) and a high-fat (60% of calories from fat) diet for 7 d each according to a randomized, crossover design. Six subjects were studied for an additional week on a mixed diet (45% of calories from fat). For each subject, total caloric intake was identical on all diets and was intended to provide the subject's maintenance energy requirements. All subjects spent days 3 and 7 of each week in a whole-room indirect calorimeter. Diet composition did not affect total daily energy expenditure but did affect daily nutrient oxidation by rapidly shifting substrate oxidation to more closely reflect the composition of the diet. These results show that diet composition can affect substrate oxidation without producing measurable effects on total energy expenditure.

Adult

Feasibility of universal screening mammography. Lessons from a community intervention.

It is estimated that 44,500 American women will die of breast cancer in 1991. The breast cancer screening guidelines of the American Cancer Society and the National Cancer Institute calling for annual mammography for all women older than 50 years have been endorsed by numerous professional groups. Third-party reimbursement for screening mammography is becoming more prevalent, and payment for screening mammography is now a Medicare benefit. Our studies, conducted as part of a National Cancer Institute grant to increase the routine use of screening mammography and clinical breast examination in women 50 to 75 years of age, have uncovered a number of significant barriers to the implementation of screening guidelines among women, primary care physicians, and providers of mammography services. These barriers, as well as methods to assure the quality of mammography, need to be addressed before universal screening is feasible.

Aged

Identification of hydroxyalkenals formed from omega-3 fatty acids.

The highly toxic lipid peroxidation product, 4-hydroxynonenal, is formed from the decomposition of hydroperoxides of omega-6 fatty acids. In this study the analogous hydroxyalkenals formed from the decomposition of hydroperoxides of omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) were isolated and identified using TLC densitometry, HPLC and GC/Mass Spectrometry. The major hydroxyalkenal formed from both fatty acids was a diene analog of 4-hydroxynonenal, 4-hydroxynona(2,6)dienal, while 4-hydroxyhexanal was a minor product. Measurement of specific omega-3 lipid peroxidation products may be important in studies using dietary fish oil.

Aldehydes