The influence of left ventricular filling pressure on atrial contribution to cardiac output. The influence of left ventricular filling pressure on the atrial contribution filling pressure and atrial contribution was seen in studies done at baseline (PCW (r=-.53, p less than .025), as well as in studies done after PCW was modified by volume expansion and/or nitrates (r=-.53, p less than .005). At baseline, atrial contribution averaged 9.3 +/- 1.3 c.c./M.2 in patients with PCW less than 20 mm. Hg, while it was only 2.4 +/- 1.2 c.c./M.2 in patients with PCW greater than or equal to 20 mm. Hg (p less than .005). Atrial contribution was significantly greater in patients who had no history of heart failure when they were volume loaded to a PCW above 20 mm. Hg than in patients with impaired ventricular function whose baseline PCW was above 20 mm. Hg. Thus, atrial contribution tends to be less effective in augmenting cardiac output when filling pressure is already elevated, particularly in patients with impaired left ventricular function.


Value and limitations of technetium-99m stannous pyrophosphate in the detection of acute myocardial infarction. Technetium-99m stannous pyrophosphate (99mTc-PYP) myocardial imaging was performed in 436 consecutive patients for the evaluation of chest pain and suspected acute myocardial infarction (AMI). Scintigrams were assessed independently by three observers with a 90% interobserver agreement. In 134 patients with documented AMI (97 TRANSMURAL, 37 NONTRANSMURAL), THE SENSITIVITY OF 99MTc-PYP imaging was significantly lower in patients with nontransmural AMI (41%) than in patients with transmural AMI (78%), 99mTc-PYP imaging correctly localized the site of transmural infarction in 53 patients (70%). A diffuse 99mTc-PYP uptake was found in nine (10%) of 91 patients with positive scintigrams: six of these had a transmural AMI and three nontransmural AMI. In 226 patients without AMI, the specificity of infarct imaging was 95%. A false-positive scintigram was found in 0%, 8%, 9%, and 2% of patients with unstable angina, progressive angina, stable angina, and noncardiac chest pain, respectively. A diffuse uptake was found in six (54%) of 11 patients with false-positive scintigrams. No patient with the clinical diagnosis of noncardiac chest pain showed discrete uptake. In 76 patients with uncertain diagnosis for AMI, 99Tc-PYP imaging was considered of value in 11 patients with ventricular conduction defects (two patients with WPW syndrome, nine patients with LBBB). These data suggest that: 1. 99mTc-PYP imaging is moderately sensitive in detecting and localizing transmural AMI and is insensitive in detecting nontransmural AMI; 2. A discrete 99mTc-PYP uptake is highly specific for AMI; 3. a diffuse uptake is neither sensitive to, nor specific for AMI. Myocardial imaging with 99m-Tc-PYP is of clinical value when the standard electrocardiographic and enzymatic techniques are inadequate for an accurate diagnosis of AMI.


Treatment of a case of lanatoside C intoxication with digoxin-specific F(ab')2 antibody fragments. In animal experiments arrhythmias induced by cardiac glycosides which prove fatal if untreated can be terminated by administration of glycoside-specific antibodies. Immunotherapy with digoxin-specific antibody fragments had hitherto only been employed on one occasion, namely in a person who had taken a massive overdose of digoxin with suicidal intent and who had failed to respond to symptomatic treatment. The present paper describes the use of F(ab')2 fragments of digoxin-specific antibodies in a female patient with lanatoside C intoxication to treat the associated life-threatening cardiac arrhythmia. The arrhythmia was rapidly terminated and normal sinus rhythm was restored. Treatment with the heterologous antibodies did not cause any side-effects.


The post-pulmonary infarction syndrome.

The post-pulmonary infarction syndrome. Following pulmonary infarction, three patients developed the classical signs and symptoms of the Dressler syndrome associated with persistent left pleural effusion. Each responded dramatically to corticosteroid therapy. While the pathogenesis of this "Post-Pulmonary Infarction syndrome," like the Dressler syndrome, is unclear, the response to corticosteroid therapy is both dramatic and diagnostic and may spare the patient prolonged discomfort and unnecessary diagnostic procedures.


Summary of measurements of employee exposure to airborne dust and fiber in sixteen facilities producing man-made mineral fibers. The results of an industry-wide study to determine the exposure of workers to man-made mineral fibers are summarized. The purpose of the study was to determine current employee exposures to airborne fibers and to utilize results to estimate past exposures. Measured exposures of workers to airborne total particulate matter and fibers are presented; samples were evaluated by phase contrast and electron microscopy. Results of the three year study, which encompassed 16 facilities and over 1500 eight hour samples, show that although there is a wide variation in concentrations of airborne fibers and particulate matter between and within the facilities surveyed, the concentrations of airborne particulate matter and fibers are generally less than 2.5 mg/m3 and 0.5 fibers/cm3, respectively. The norminal fiber size of the fibers manufactured and average airborne fiber concentration were highly correlated.


Fume hoods, open canopy type--their ability to capture pollutants in various environments. Using field observations, modelling techniques and theoretical analysis, parameters describing the performance and collection efficiency of large industrial canopy fume hoods are established for, a) steady state collection of fume and b) collection of plumes with fluctuating flowrates. Hopper and pool type hoods are investigated. A baffle plate arrangement for placement within hoods is proposed. It prevents recirculation and spillage of fume. Temporary storage of fume surges within the hood is shown to be possible. At a cost of $6 per m3/hr ($10 per ft3/min) of installed fume control system capacity the arrangement promises to save millions of dollars on large new installations and to significantly improve the collection efficiency of many existing systems. A practical application of the results is proposed for the design of electric arc furnace canopy hoods.


Application of control technology developed in the polyvinyl chloride industry to polymerization processes using acrylonitrile. Polymerization processes for PVC are sufficiently similar to acrylonitrile polymerization processes to allow a significant transfer of control technology. This transfer should be of value to manufacturers of polyacrylonitrile, ABS/SAN resins, nitrile elastomer and latex who will need to install extensive additional controls to comply with the new permanent standard for acrylonitrile scheduled to be issued by OSHA in late 1978. Control strategies and individual controls developed to limit worker exposure in the PVC industry are described and evaluated relative to applicability to acrylonitrile polymerization processes.


Benzene exposure in the rubber coating industry--a follow-up. This paper is a follow-up on thirty-eight workers exposed from 1 to 24 years to average benzene concentrations generally between 5 and 50 ppm, but as high as 90 (peak of 140) in the case of one worker. One individual was diagnosed as suffering from mild benzene poisoning and a small number of workers in the group had blood changes considered abnormal, but blood dyscrasia or leukemia has not developed in 13 years after benzene use was terminated in 1964. The population studied was small, but the data, nevertheless, would appear to support the former ACGIH TLV of 25 ppm. One case of mild benzene poisoning reported from benzene exposures of the order of 40 ppm suggests, however, that the margin of safety may be small. The current ACGIH TLV of 10 ppm seems reasonable in the light of our findings.


Assessment of hazardous air pollutants from disposal of munitions in a prototype fluidized bed incinerator. As part of the control technology development for the disposal of waste munitions, an assessment of potential emissions of hazardous air pollutants from a prototype fluidized bed incinerator was conducted. Assessment program elements included identification of potentially toxic emissions through material input analysis and computer simulation modeling of the combustion cycle; development of emission limitations criteria for substances having no present air pollution emission standards; evaluation and development of analytical procedures; and design of a sampling system to condition an emission stream characterized by high temperature and humidity resulting from burning water slurries of explosive materials. Emphasis is placed on the potential emission of nickel and its compounds, particulate and vapor emissions of cyanides, nitrogen oxides, and TNT and RDX energetic residuals.


Annoyance potentials of air pollution odors. The various parameters of odor sensation can be evaluated to yield their relative potential to cause annoyance. The effect of prolonged exposure to odors on the human sense of smell is not clear, but circumstantial evidence points to the possibility of deleterious changes.


Measurement of atmospheric vinyl chloride. Methods for atmospheric vinyl chloride measurement have been reviewed. The lowest detection limits and most specific measurement are achieved by scrubbing atmospheric samples with activated charcoal, desorbing the vinyl chloride, and assaying it by gas chromatography (GC). NIOSH currently recommends collecting samples using tubes packed with 150 mg of coconut shell charcoal, desorbing with carbon disulfide, and analyzing by GC equipped with flame-ionization detection (FID); the method is capable of detecting less than 1 ppm vinyl chloride and has an apparent recovery of abo the ppb level with no loss of accuracy or precision. Some field methods, such as infrared analysis and conductivity measurement, are capable of detecting 1 ppm or lower but are subject to interferences by other contaminants; th-y could be useful for evaluating sources of vinyl chloride leaks and for continuous monitoring. Permeation tubes are superior to gravimetric or volumetric methods for generating atmospheres of known vinyl chloride concentration.


Simplified description of adsorption breakthrough curves in air cleaning and sampling devices. Breakthrough curves of organic vapors through a charcoal bed are analyzed by a simplified Theory of Statistical Moments. It is shown that this theory adequately describes the dependence of the shape of the breakthrough curve on concentration of vapor, velocity of air, particle size of charcoal, and length of the bed.


A calibration system for producing known concentrations of mercury vapor in air. This paper describes the construction and evaluation of a system capable of producing well-defined test mixtures of mercury in air, or other diluent gas, at mercury concentrations between zero and 16 mg/M3. The various parameters that affect the generation system and their interactions are discussed and data is given for the calibration of several different mercury monitors.


The toxicity of hexachloroethane in laboratory animals. Studies were conducted to assess hazards to personnel exposed to hexachloroethane (HCE) in an industrial setting. Acute testing in laboratory animals indicated HCE was moderately toxic orally and could produce reversible eye irritation and mild skin irritation. Percutaneous absorption appeared to have no practical significance. The subchronic vapor inhalation toxicity was determined in rats, guinea pigs, Japanese quail and dogs in a 6-week test, monitoring pulmonary function changes, teratogenicity and operant behavioral changes in addition to clinical chemistry, hematology and histopathology. Concentrations of 260 ppm HCE vapor caused severe systemic effects in dogs, moderate effects in guinea pigs and rats and almost no responses in quail. No differences were found between exposed and control animals at 3 months after termination of these exposures. Minimal toxic effects were found following similar 6-week tests at levels of 48 ppm with no detectable changes at 15 ppm of HCE.


Collaborative study of reference vinyl chloride charcoal tubes. The reference vinyl chloride charcoal tubes generated by a permeation technique are evaluated by collaborative testing. The statistical analysis of Youden's method provides an estimate of replication error, sample generation error, and interlaboratory error.


A short-term test to predict acceptable levels of exposure to airborne sensory irritants. An animal model has been developed using decrease in respiratory rate in mice as an index of sensory irritation. Concentration-response relationships were developed for 11 sensory irritants. The RD50, defined as the concentration associated with a 50% decrease in respiratory rate, has been shown to have a predictable relationship to sensory irritation in man. By extending the accepted toxicological principle that the ratio lethal/toxic/effective/ineffective/acceptable in diet is 10/1/10(-1)/10(-2)/10(-3) dosage units to air concentrations, exposure guidelines can be proposed for TLVs, STELs, etc.


Interlaboratory comparison of blood lead determinations. Results are presented for an interlaboratory proficiency study of blood lead determinations. Samples were pooled from individuals occupationally exposed to lead. Performance of individual laboratories is compared over a two year period. With increased emphasis in recent years on proficiency studies of this type, agreement between laboratories has been somewhat improved, but blood remains a difficult matrix in which to measure lead concentration.


Health hazard from occupational exposure to metallic copper and silver dust. This review of the toxicity and occupational hazard from exposure to metallic copper and silver dust was undertaken to examine the bases for the current standards and to suggest an alternative approach to controlling potential occupational hazard in conditions where exposures are limited to the prime metals. There are no data to suggest that exposure to silver or copper metal dust has produced remarkable disease in man. Further, there is no reason to consider the dust from either of these metals to be anything but nuisance particulate as defined by the ACGIH. They should, therefore, be regulated as such at the recommended level of 10 mg/m3.


Current confidence in occupational health. Little if any real justification is found for current apprehensions about health hazards in the work place. However, communications from some who are responsible for defining and controlling hazards tends to destroy confidence, rather than to build it up, as their knowledge and authority should obligate them to do. I attribute the unfortunate effect of their statements to confusion of association with cause and effect, reliance upon inappropriate experimental animal models, confusion of models with reality, irresponsible talk of conceivable possibilites rather than of realistic probabilities, and haste to announce suspicions before they can be confirmed or denied.


Pollution of delivery ward air by nitrous oxide--methoxyflurane. Pollution of delivery ward atmosphere by analgesic gases and vapors has not been studied as extensively as pollution of operating theaters. This study shows that delivery room atmosphere is polluted by methoxyflurane (0.5--0.8 ppm) and nitrous oxide (300--540 ppm) and that a local gas exhaust system reduces the concentration by half.


Respiratory response of guinea pigs to oil mists. Respiratory function was measured in guinea pigs exposed for one hour to submicrometer oil mists. Five oils were used: medicinal grade mineral oil, laboratory grade paraffin oil, light lubricating oil, unused motor oil and used motor oil. The last three oils were also studied after having been reacted with sulfur dioxide. No alterations were produced by exposure to any of the oils at concentrations of 10 or 40 mg/m3. At concentrations above 200 mg/m3 both the reacted and unreacted light lubricating oil caused a decrease in compliance which remained throughout the post-exposure period. Although the average flow-resistance of the group was increased by the unreacted unused motor oil and by the reacted used motor oil, the variation in response was too great to make this response statistically significant. The fact that reaction of the oils with sulfur dioxide did not increase irritant action indicates that the reaction products with sulfur dioxide are not acutely irritant.


Effect of oil mists on the irritancy of sulfur dioxide. I. Mineral oils and light lubricating oil. The increase in pulmonary flow resistance in unanesthetized guinea pigs was used to assess the effect of sub-micrometer oil aerosols on the response to sulfur dioxide. At a concentration of about 10 mg/m3 neither a medicinal grade mineral oil nor a light lubricating oil altered the response when given simultaneously with 1 or 10 ppm sulfur dioxide. The naphthenic medicinal oil at 100 mg/m3 failed to protect against 50 ppm sulfur dioxide when administerd simultaneously. A 30-minute pre-exposure, however, conferred complete protection. A paraffinic laboratory grade mineral oil conferred protection when given simultaneously but was less effective when the pre-exposure protocol was used.


Evaluation of zinc protoporphyrin in an occupational environment. Zinc protoporphyrin (ZnP) has been identified by several investigators as the predominant fluorescent porphyrin accumulating in erythrocytes as a result of chronic lead absorption or iron deficiency anemia. This report describes an evaluation of a new portable hematofluorometer for the determination of ZnP in finer puncture or venous blood samples. Samples were obtained from a number of employees in various job categories at steel operations throughout the United States to study the utility of ZnP as a biologic monitoring method in the occupational environment. Urinary lead, urinary aminolevulinic acid and blood lead were also determined on the same employees to examine any relationships among these measurers and to estimate a biologic threshold limit value for ZnP. The results of this investigation show that there is little elevation of the ZnP level with increasing blood level until the blood lead concentration reaches the area of 50--60 micrograms/dl. A biologic threshold level of 300 micrograms/dL, which correlates with a blood level of 60 micrograms/dL, is suggested as a guideline value for identifying workers requiring further investigation.


A retrospective epidemiological study of morbidity at a large western copper smelter. Smelter workers were compared with employees at the mine, concentrator and refinery in an attempt to discover if the smelter environment has an effect on morbidity. The data for the study consisted of weekly indemnity insurance claim forms. It was found that the refinery, rather than the smelter, had the highest percent of employees submitting claims. Other major comparisons of morbidity among the four plants also showed the refinery to be highest, with the smelter closer to the mine and concentrator. This pattern was found to hold for respiratory disease classifications as well as overall morbidity levels.


Botanically what is raw cotton dust?

Botanically what is raw cotton dust? The objective of this study was to determine the specific botanical ingredients present in respirable raw cotton dust. Significant differences in content of gross leaflike (bractcontaining) trash were found between several grade divisions of raw cottons. For example, higher grades of raw cotton (strict low middling = SLM) contained less leaflike trash than lower grade cottons (low middling = LM). The potential for production of fine particulate from botanical trash materials plus lint and linters was determined in the laboratory by an abrasive milling test. Bract and wood fragments were the most friable of all plant materials found in raw cottons whereas seed meat, lint, linters and seed coat were the least friable. Respirable (10 less than 10 micrometers) raw cotton dusts associated with the processing of middling, SLM and LM raw cottons were predicted to contain the following % weight composition of specific vegetable ingredients: leaflike = 70--72%, stem = 13--18%, bark = 3--8%, exocarp-mesocarp = 3.6%, endocarp = 1--2% and seed = 0.5--2%. Bract is the most abundant component in respirable raw cotton dust.


The computerization of industrial hygiene records. A program for computerizing the results of industrial hygiene monitoring data has been developed and implemented. The methodology and approaches taken in data collection, retrieval, and utilization are presented.


How much should a certified industrial hygienist know about health physics? Based on the classical definition of an industrial hygienist, it is obvious that a certain level of competence in health physics aspects is required. The converse may also be true. Individuals in both professional organizations are urging more interfacing between the two groups. In light of this, the author presents a matrix which illustrates the progressive steps involved in ionizing radiation hazard judgment, based on the classical industrial hygiene definition. The author then presents his opinion (using examples from literature and his own experience) as to the delineation of areas in which a certified hygienist should be able to handle potential ionizing radiation hazards successfully. It is stressed that the hygienist must, in addition, be able to know when to consult a qualified health physicist in situations which require a more advanced level of expertise.


Adjusting occupational exposure limits for moonlighting, overtime, and environmental exposures. A mathematical model is used to predict relative body burdens of inhaled contaminants in workers who work two jobs or overtime, or who experience off-the-job exposure to air contaminants. Expected "peak" or maximum body burdens from multiple exposures are compared to those expected from the "normal" occupational exposure on which TLVs and Permissible Exposure Limits (PELs) arebased (five 8-hour days per week with zero off-the-job exposure). The model is designed to predict what adjustments to the TLVs and PELs are necessary to avoid accumulation of excess peak body burdens of contaminants from the additional exposures incurred. The general application of models to determine occupational exposure limits is reviewed, and several models are compared.


An atomizer of high stability.

An atomizer of high stability. An atomizer having excellent stability and requiring little maintenance was tested. The basic design incorporates modifications to a previously described atomizer of Liu and Lee. This modified atomizer yielded a constant particle size and concentration output that varied by less than +/- 2% of the mean value for 25 hours. Liquid is aspirated at the rate of 100 mL/hr., making the atomizer suitable for use with solvents of various volatilities. The orifices, critical to the performance of the atomizer, are easily cleaned or replaced.


A validation procedure for air sampling-analysis systems. Validation of solid sorbent air sampling-analytical systems used to evaluate employee exposures to substances in the work place air is a fundamental part of any industrial hygiene air sampling program. In April, 1977, the National Institute for Occupational Safety and Health (NIOSH) published "Documentation of the NIOSH Validation tests", as part of the Standards Completion Project. This paper presents an alternative validation procedure which is more easily understood, is more rigorous, and provides for greater accuracy and precision.


Analysis of ethylene oxide--worker exposure. A personal air sampling method for assessing individual worker exposure to ethylene oxide has been developed. The method is based on trapping ethylene oxide in dilute sulfuric acid where it is converted to ethylene glycol. The ethylene glycol is determined by gas chromatography using a glass column packed with 5% Igepal CO-990 on Teflon T-6. This column produces linear calibration curves and symmetrical peaks. The method has been shown to recover 94.2% ethylene oxide in the 1 to 8 ppm concentration range. The sampling technique is independent of flow and sample size. Advantages over the NIOSH method are discussed.


Cardiac load and function in hypertension. Ultrasonic and hemodynamic study. On the basis of echocardiographic measurements, 46 patients with established, uncomplicated primary hypertension (diastolic pressure = 100 mm Hg) were classified as: those with a normal-sized heart (Group I, 13 patients); those with left ventricular concentric hypertrophy (Group II, 19 patients); and those with left ventricular hypertrophy and enlargement (Group III, 14 patients). Eighteen age-matched healthy subjects were investigated as the controls. The function of both the left and right ventricle, evaluated by the stroke index-filling pressure relation and by the mean rate of ejection, was maintained in Group I, augmented in Group II and reduced in Group III, in comparison with the controls. Left ventricular mean rate of circumferential fiber shortening (Vcf) was normal in Group I, significantly augmented in Group II and definitely reduced in Group III. It could not be established whether the divergent variation from normal of the Vcf in Groups II and III reflected opposite changes in ventricular contractility or in afterload (wall stress during ejection), or both. However, the parallel functional pattern of the right and left ventricle in these two groups suggests a functional interdependence of the two sides which cannot be interpreted in terms of afterload but is best explained by changes in the contractile state of the whole heart.


Nifedipine therapy for refractory coronary arterial spasm. Nifedipine was evaluated in the management of eight patients with intractable coronary arterial spasm. All had Prinzmetal's variant angina, normal or mildly abnormal coronary arteriograms, and a positive ergonovine maleate provocative test. Anginal attacks occurred at least three times a week in all patients during isosorbide dinitrate therapy. All patients had a decrease in frequency of ischemic attacks with nifedipine. Seven patients underwent repeat Holter monitor evaluation, which confirmed the absence of ischemic changes while they were taking nifedipine. When nifedipine dosage was decreased.or therapy discontinued in six patients, all experienced a recurrence of anginal attacks. Two patients had minor side effects, which required a decrease in the dose of nifedipine. Nifedipine was well tolerated, and no major complications occurred with its use. Nifedipine appears to be effective in the management of patients with symptomatic coronary arterial spasm and normal or mildly abnormal coronary arteriograms. Our data justify further investigation of nifedipine for treatment of such patients.


Nifedipine in the treatment of Prinzmetal's (variant) angina. The clinical response to therapy with the calcium-blocking agent nifedipine was assessed in 12 patients with variant angina pectoris who were 44 to 67 years old. Five patients had vasospasm of the left anterior descending coronary artery, and seven had spasm of a dominant right coronary artery. Before nifedipine therapy, the frequency of anginal attacks per 24 hour period ranged from 1 to 12, with ventricular tachycardia accompanying ischemic episodes in 7 of 12 patients and high grade atrioventricular block occurring in 2 patients. After therapy with nifedipine, 11 of 12 patients had initial relief of symptoms, and 7 of the 11 had long-term relief. Withdrawal of nifedipine led to recurrence of angina on six occasions in four patients. Provocative testing in the cardiac catheterization laboratory by means of the cold pressor test in one patient and ergonovine maleate in another before and after nifedipine administration showed that this agent can block both alpha adrenergic- and regonovine-induced vasospasm. Nifedipine may have a significant role in the therapy of angina caused by coronary spasm.


Nifedipine: a myocardial protective agent. The effectiveness of the calcium antagonist nifedipine in preserving postischemic myocardial function and structural integrity was experimentally demonstrated in isolated rabbit hearts, in conscious dogs subjected to myocardial infarction, in open chest anesthetized dogs with normothermic regional ischemia induced for 1 to 2 hours and in dogs undergoing hypothermic global ischemia for 2 hours followed by 2 hours of reperfusion. Nifedipine had a beneficial effect on postischemic myocardial stiffness and mitochondrial calcium accumulation, which were correlated. Administration of nifedipine at the onset of myocardial infarction increased blood flow to ischemic zones of myocardial infarction and resulted in less loss of creatine kinase. It reduced by two- to three-fold the volume of the ischemia-reperfusion injury induced by left anterior descending coronary arterial occlusion and release and preserved indexes of hemodynamic function. Nifedipine was found effective in protecting myocardial performance and structure after 2 hours of global ischemia during hypothermic cardiopulmonary bypass. It is suggested that this agent may be useful as an adjunct to cold cardioplegia in man for enhanced myocardial protection during cardiac surgery.


Atrial reflexes and renal function.

Atrial reflexes and renal function. Distension of small balloons in the venous-atrial junctions results in an increase in heart rate, urinary flow and sodium excretion. Two types of atrial receptors are described: one type, histologically known, discharging into myelinated fibers, and a second type, discharging into nonmyelinated ("C") fibers. These responses are mediated by the myelinated fibers. Experiments have shown that simulation of receptors discharging into the large myelinated vagal fibers is responsible for a reflex increase in heart rate mediated only by sympathetic nerves and for an increase in urinary flow. The efferent pathway of the diuretic response is shown to be nervous and hormonal. Stimulation of atrial receptors causes (1) a reduction of activity in nerves to the kidney, causing an increase in both urinary volume and sodium excretion, and (2) the release of a blood-borne agent, possibly diuretic, that increases urinary volume but does not affect sodium excretion.


Cardiac pumping ability in rats with experimental renal and genetic hypertension. In two experimental models of established hypertension in the rat (two kidney, one clip renal and genetic hypertension), the maximum by which stroke volume and cardiac output could be increased during an acute preload stress was significantly reduced despite the concomitant development of left ventricular hypertrophy. Reversal of cardiac hypertrophy by prolonged treatment with methyldopa (range 3 to 6 weeks) during the established phase of spontaneous hypertension normalized arterial blood pressure and improved ventricular pumping ability. The improved performance was in part due to reduced impedance to ventricular ejection because it did not persist when peripheral resistance was increased by an acute administration of phenylephrine hydrochloride. Thus, hemodynamic as well as structural factors contribute to alterations in cardiac function during the chronic established phase of arterial hypertension.


Left bundle branch block: angiographic segmental wall motion abnormalities. Ventricular wall motion as studied with contrast ventriculography has been judged normal in the few previously reported cases of patients with left bundle branch block who have neither coronary artery disease nor diffuse cardiomyopathy. However, recent echocardiographic studies have demonstrated a high frequency of segmental asynergy of the septal wall in such patients. In this study left ventricular wall motion was analyzed in 15 patients with left bundle branch block and without significant coronary artery disease or diffuse cardiomyopathy. Biplane cineangiograms from these patients were compared with those from 100 consecutive patients with normal intraventricular conduction and without coronary artery disease or cardiomyopathy using two techniques: qualitative visual inspection and a computer-assisted quantitative method. By qualitative review, 6 of 15 patients with left bundle branch block had regional akinesia or dyskinesia as compared with none of 100 patients with normal intraventricular conduction (chi square = 42.3; P less than 0.001). By quantitative review, 10 of 12 patients with left bundle branch block had abnormal wall motion along at least one hemiaxis. It is concluded that angiographic regional wall motion abnormalities are common in patients with left bundle branch block, even in the absence of coronary artery disease or diffuse cardiomyopathy. The abnormalities may result from the abnormal sequence of ventricular activation rather than from myocardial fibrosis.


Performance of the failing and nonfailing right ventricle of patients with pulmonary hypertension. Hemodynamic performance of the right ventricle was measured in 34 patients: 17 with pulmonary hypertension, 9 with pulmonary hypertension and right ventricular failure and 8 control subjects. Among the patients with pulmonary hypertension who did not have right ventricular failure, right ventricular maximal isovolumic rate of development of ventricular pressure (dP/dt) was significantly elevated (P less than 0.001), whereas maximal 1/P dP/dt and maximal velocity of contractile element shortening (Vmax) were comparable with values observed in control subjects. The patients with pulmonary hypertension who had right ventricular failure also showed an augmented right ventricular maximal dP/dt (P less than 0.001) and normal 1/P dP/dt and Vmax. These observations indicate that in pulmonary hypertensive heart disease, even when the right ventricle failed in a clinical sense, the contractile effort was normal. Consequently, right ventricular failure may develop in patients with pulmonary hypertensive heart disease even though the cardiac muscle performs normally as a contractile tissue.


Detection of left ventricular functional reserve by supine exercise hemodynamics in patients with severe, chronic heart failure. Hemodynamic changes during exercise were evaluated in 20 patients with severe, chronic congestive heart failure. Two groups were identified by their stroke work response to maximal exercise. Group I (eight patients) showed an increase in stroke work index. This occurred because the stroke volume increased and the difference between mean systolic pressure and left ventricular filling pressure increased. Group II (12 patients) showed a decrease in stroke work index. This occurred because stroke volume decreased while the difference between mean systolic pressure and left ventricular filling pressure did not change. Despite hemodynamic differences, the groups could not be distinguished by the usual clinical criteria for heart failure including etiology, New York Heart Association functional class, heart size on chest X-ray film or duration of heart failure. Clinical criteria are relatively insensitive in predicting the exercise hemodynamics of any given patient with chronic severe heart failure. Determining the exercise hemodynamics may be helpful as a means of assessing left ventricular functional reserve in heart failure. Prognostic implications, drug therapy and prescription of activities may require adjustment based on this spectrum of hemodynamic response to exercise in patients with chronic heart failure.


Relation between the precordial projection of S-T segment changes after exercise and coronary angiographic findings. The recent introduction of electrocardiographic mapping permits measurement of the precordial area and severity of exercise-induced S-T segment changes. This study was designed to compare this technique with a modified 12 lead electrocardiogram in defining the degree and site of coronary artery disease. One hundred patients, who later had diagnostic coronary arteriography, underwent an exercise test using both 16 point precordial mapping and a modified 12 lead electrocardiogram. The sensitivity of electrocardiographic mapping (96 percent) for the diagnosis of coronary artery disease was significantly greater than that of the modified 12 lead electrocardiogram (80 percent). However, the specificity of the two lead systems was similar. Typical precordial projections of S-T segment change were found when the left main stem or proximal left anterior descending coronary artery were narrowed or when there was isolated disease of the left anterior descending or right coronary artery. Widespread precordial changes were found in patients with three vessel disease. Although there was no significant difference in the sensitivity (66 percent) and specificity (100 percent) of electrocardiographic mapping and of the 12 lead system in identifying three vessel disease, there was a significant difference in sensitivity (electrocardiographic mapping 74 percent, 12 lead system 42 percent) in identifying isolated single vessel disease. In addition, information regarding the presence of left main stem or proximal left anterior descending coronary arterial narrowing was obtained only with electrocardiographic mapping. The superiority of electrocardiographic mapping over the modified 12 lead electrocardiogram has been shown, and clinical application of this technique should be useful in the management of patients presenting with chest pain.


Hemodynamic response to exercise after propranolol in patients with mitral stenosis. Hemodynamic response to exercise before and 10 minutes after propranolol (5 mg intravenously) was studied in 10 young patients with pure mitral stenosis who had normal sinus rhythm and no cardiac failure. After propranolol the mean heart rate and cardiac index at rest were lower than during the control state (respectively, 95 +/- 4 versus 82 +/- 3 beats/min, P less than 0.005; 3.4 +/- 0.2 versus 2.8 +/- 0.1 liters/min per m2, P less than 0.025). As a result, the mean pulmonary wedge pressure and mean mitral valve gradient at rest were lower (respectively, 22 +/- 2 versus 18 +/- 2 mm Hg, P less than 0.005; 24 +/- 2 versus 17 +/- 2 mm Hg, P less than 0.001). During exercise after propranolol the values of pulmonary wedge pressure and mitral valve gradient were lower than control values during exercise (respectively, 39 +/- 3 versus 30 +/- 2 mm Hg, P less than 0.005; 44 +/- 3 versus 32 +/- 3 mm Hg, P less than 0.005), again because of the lower heart rate and cardiac index (130 +/- 6 versus 104 +/- 6 beats/min, P less than 0.001; 4.6 +/- 3 versus 3.7 +/- 2 liters/min per m2, P less than 0.01). Left ventricular end-diastolic pressure and stroke index showed no significant changes. Thus, propranolol may benefit patients with pure mitral stenosis with sinus rhythm and no cardiac failure whose symptoms occur during those reversible conditions characterized by an increase in heart rate or cardiac output, or both.


Histopathologic correlates of left posterior fascicular block. Thirteen hearts from subjects (10 male, 3 female; mean age 65 years) with left posterior fascicular block were studied. Left posterior fascicular block was associated with right bundle branch block in nine cases and alternated with left anterior fascicular block in three. In nine of the patients, the conduction disorders were observed during an episode of acute myocardial infarction. Of these nine patients, four showed interruptive lesions at the level of the posterior radiation of the left bundle or of the posterior portion of the main left bundle branch. Two were found to have severe alterations scattered throughout the left bundle branch system: One of them had alternating left anterior and left posterior fascicular block; and the other manifested complete heart block in the course of her illness. No interruptive changes of the posterior fibers were found in three cases in which the heart was obtained early after death. All 9 patients had severe coronary artery disease (six had triple vessel disease and three of the six had a left main coronary arterial stenosis or obstruction; two patients had double vessel disease). Among the four patients with chronic left posterior block, three were found to have heavy calcifications of the left side of the cardiac skeleton; the remaining one had diphtheritic myocarditis. All had major alterations of the left-sided conduction system that were consistently maximal at the level of the posterior fibers or posterior portion of the main left bundle branch. In two of these patients scattered lesions were found throughout the left bundle branch fibers; one had alternating left anterior and left posterior fascicular block and the other had complete heart block. In general, the alterations underlying left posterior fascicular block were less widely spread than in left anterior fascicular block; however, they were more severe and more proximally located.


Incidence, determinants and significance of fixed retrograde conduction in the region of the atrioventricular node. Evidence for retrograde atrioventricular nodal bypass tracts. Of 104 consecutive patients studied in our laboratory with His bundle electrograms, atrial and ventricular pacing and the atrial and ventricular extrastimulus techniques, 18 patients in whom the existence and utilization of ventriculoatrial (V-A) bypass tracts were excluded demonstrated evidence for fixed and rapid retrograde conduction in the region of the atrioventricular node (A-V) as suggested by the following: (1) short (36 +/- 2 msec [mean +/- standard error of mean]) and constant retrograde H2-A2 intervals during retrograde refractory period studies; (2) significantly (P less than 0.025) better V-A than A-V conduction; (3) significantly (P less than 0.025) shorter retrograde functional refractory period of the V-A conducting system than of the A-V conduction system; and (4) the retrograde effective refractory period of the A=V nodal region was not attainable in any of the 18 patients. Fourteen of the 18 patients (77 percent) had a history of palpitations and 10 (51 percent) had documented paroxysmal supraventricular tachycardia; in 13 (72 percent) single echoes or sustained reentrant supraventricular tachycardia, or both, could be induced during atrial pacing or atrial premature stimulation studies, or both. During tachycardia all these 13 patients had a short (37 +/- 2.4 msec) and constant conduction time in the retrograde limb (H-Ae interval) of the reentrant circuit that was identical to the H2-A2 interval. In conclusion, fixed and rapid retrograde conduction in the region of the A-V node (1) is seen in approximately 17 percent of patients, (2) is associated with a large incidence of reentrant paroxysmal supraventricular tachycardia, and (3) suggests the presence of A-V nodal bypass tracts (intranodal or extranodal functioning in retrograde manner).


Reciprocal tachycardias using accessory pathways with long conduction times. Three patients with reentrant tachycardia are described who had an accessory pathway with a very long conduction time that was incorporated in the tachycardia circuit. The accessory pathway was able to conduct in one direction only, in retrograde manner in two patients and in anteriograde manner in the remaining patient. Evidence is presented that reveals that in the first two patients the accessory pathway was septally located, had completely bypassed the normal atrioventricular (A-V) conduction system, had properties of decremental conduction, and had an atrial exit close to the coronary sinus and a ventricular exit relatively far from the atrioventricular A-V ring. In the third patient, who manifested wide QRS complex during tachycardia, the ventricular end of the accessory pathway seemed to be located close to the right ventricular apex. The atrial end of the pathway could not be localized exactly.


The risk of pericardiocentesis.

The risk of pericardiocentesis. The risk and potential risk factors of pericardiocentesis were assessed by a review of a series of 52 pericardiocenteses comprising all those performed in the cardiac catheterization laboratory of one institution from 1971 to 1978. On the basis of the operative results, the patients were separated into two groups for comparison; Group I comprised all patients with a successful uncomplicated (35) pericardiocentesis and Group II all those with a nonproductive (16), nontherapeutic (1) or complicated (8) pericardiocentesis. Complications consisted of one death, one cardiac arrest, one aspiration of a subdiaphragmatic abscess and five ventricular punctures without adverse sequelae. Among the patients who had a nonproductive pericardiocentesis, the condition of 11 had probably been misdiagnosed but at least 4 had a false negative pericardiocentesis. Comparison of the two groups showed no significant difference in the incidence of cardiac tamponade or in the clinical presentation based on historical, physical, electrocardiographic, roentgenographic or echocardiographic findings of pericardial disease. Pericardiocentesis was usually successful when performed for suspected malignant pericardial effusion but often unsuccessful when performed for suspected hemopericardium. Anatomically, all patients in Group II had either minimal or loculated posterior pericardial effusion. It is concluded that pericardiocentesis can be performed at a low risk that can be further minimized by consideration of the disease process and the anatomic location of the pericardial fluid.


Oxygen deprivation and early myocardial contractile failure: a reassessment of the possible role of adenosine triphosphate. The precise mechanism responsible for early contractile failure after the onset of myocardial anoxia or ischemia has attracted speculation and controversy. The simple and attractive hypothesis that adenosine triphosphate (ATP) deficiency is responsible for this failure has often been dismissed on the basis of claims that there is only a small reduction in cell ATP content at a time when contractile activity is severely reduced. The premise of this article is that the changes in cell ATP content and distribution that theoretically should occur after oxygen depletion may not have been adequately considered and that previous measurements of cell ATP content may not have been carried out at the correct time. Using an isolated rat heart preparation and high speed freeze-clamping techniques it has been possible to demonstrate that a substantial decrease in myocardial ATP and creatine phosphate content occurs after the onset of anoxia but before the onset of contractile failure. Thus, during the first 5 seconds of anoxia contractile activity remains constant whereas ATP decreases by 25 percent and creatine phosphate by 50 percent. Thereafter, contractile failure occurs and the rate of utilization of high energy phosphates declines with the cell content at a plateau or possibly increasing. These results are assessed in the light of the dynamic changes in energy metabolism occurring in early anoxia and suggest that ATP depletion in a specific cell compartment may be the primary trigger for early contractile failure.


Two dimensional echocardiographic characteristics of double outlet right ventricle. The reliability was evaluated of two dimensional echocardiography in distinguishing double outlet right ventricle from other anomalies of the great arteries. Accordingly, a combined retrospective and prospective study was conducted in 13 children with double outlet right ventricle, 12 with tetralogy of Fallot, 13 with complete d-transposition of the great arteries, 5 with congenitally corrected I-transposition and 2 with truncus arteriosus. Echographic findings using a standard long axis view in all subjects with double outlet right ventricle included (1) inability to identify a great artery arising from the left ventricle, and (2) lack of continuity between the anterior mitral leaflet and any semilunar valve. In the short axis view constant findings were (1) simultaneous imaging of both great arteries in an anterior location with the ventricular septum identified posteriorly on sweeping into the left ventricle, and (2) lack of a clockwise wraparound of the aorta by the right ventricular outflow tract. Imaging revealed that the great arteries were side by side in seven patients d-malposed in three and l-malposed in two. A modified left precordial tomographic view demonstrated both great arteries arising from the right ventricle in four of nine patients not treated surgically. In four patients with surgically repaired double outlet right ventricle, the left ventricular outflow tract had a tunnel-like configuration in the long axis view. These findings were diagnostic of double outlet right ventricle in all patients and accurately differentiated the malformation from other anomalies of the great arteries.


Pulsed Doppler echocardiographic detection of total anomalous pulmonary venous return: resolution of left atrial line. During precatheterization M mode echocardiographic examination, 33 infants were identified as having findings including right ventricular enlargement and presence of a line within the left atrial portion of the M mode tracing suggesting the possibility of cor triatiatum or total anomalous pulmonary venous return. Pulsed Doppler echocardiography was used to sample blood characteristics on either side of the left atrial line to determine which line was artifactual and which was indicative of an important structure. Five patients whose blood flow characteristics were different on either side of the left atrial line were subsequently proved to have total anomalous pulmonary venous return at cardiac catheterization. In the remaining infants blood flow characteristics were identical on either side of the line, and catheterization excluded total anomalous pulmonary venous return and cor triatriatum. In all patients who had total anomalous pulmonary venous return, drainage involved a persistent left superior vena cava, and this vascular structure was identified by pulsed Doppler examination from the suprasternal notch. Pulsed Doppler echocardiography appears to be a useful technique for resolution of left atrial lines found on M mode echocardiography.


Increased systemic vascular resistance in neonates with pulmonary hypertension. The time necessary for aortic diastolic pressure to decrease to 50 percent of an initially selected value after dissipation of the dicrotic notch (T 1/2) was determined in newborn infants with and without pulmonary hypertension. The mean T 1/2 was 671 +/- 167 msec in seven infants with clinical evidence of pulmonary hypertension and documented right to left ductus arteriosus shunting; 849 +/- 243 msec in nine infants with clinical evidence of pulmonary hypertension but no documented right to left ductus arteriosus shunting; and 457 +/- 66 msec in eight infants with hyaline membrane disease and no clinical evidence of pulmonary hypertension or a patent ductus arteriosus. The mean T 1/2 values in the former two groups were significantly different from that in the group with no pulmonary hypertension (P less than 0.01). An evaluation of factors affecting T 1/2 leads to the conclusion that the patients with pulmonary hypertension had increased systemic vascular resistance as well. This finding has important diagnostic, etiologic and therapeutic implications.


Volume studies in men with mild to moderate hypertension. The importance of salt and water in the pathophysiology of the hypertensive state is well recognized. The current study is the first to report simultaneous measurements of red blood cell mass, plasma volume, extracellular fluid and total body water levels. Studies were performed in 82 white men, 14 with normal blood pressure and 16 with low renin and 52 with normal renin hypertension. The results indicate that subjects with normal renin hypertension compared with age-matched controls are characterized by an absolute increase (1.5 liter/m2) in intracellular fluid (total body water minus extracellular fluid). Furthermore, the ratio of extracellular fluid to total body water is decreased (0.43 to 0.38). No volume differences were found between subjects with low renin hypertension and age-matched subjects with normal renin hypertension. We conclude that subjects with normal renin hypertension compared with age-matched peers are characterized by an expanded intracellular fluid and that subjects with low renin hypertension do not exhibit a unique volume disorder.


Development of pharmacodynamic tolerance to prozosin in congestive heart failure. In order to determine and compare the pharmacodynamic responses to single and multiple dose prazosin therapy in cardiac failure, 14 patients with severe low-output heart failure underwent central and regional hemodynamic measurements after random placement in one of two prazosin dosing schedules. A single 5 mg oral dose of prazosin (Group A, no. = 7) significantly increased the cardiac index and stroke volume index while significantly decreasing systemic, pulmonary and pulmonary capillary wedge pressures and vascular resistances. Hepatic plasma flow and limb blood flow increased after the single dose. Striking attenuation of these hemodynamic effects occurred when the same dose was administered after 24 hours of pretreatment with oral prazosin, 2 mg every 8 hours (Group B, no. = 7). The plasma prazosin levels of the two groups, drawn 2 hours after administration, were 24.5 and 30.5 ng/ml, respectively. Repeated administration of prazosin in patients with congestive heart failure results in rapid attenuation of its beneficial central and regional hemodynamic effects. The usefulness of this vasodilator as a preload- and afterload-reducing agent in the clinical setting of chronic congestive heart failure may be limited by the development of pharmacodynamic tolerance.


Influence of short-term oral hydralazine therapy on exercise hemodynamics in patients with severe chronic heart failure. Changes in left ventricular performance were evaluated in 14 patients with functional New York Heart Association class III or IV chronic heart failure before and after the addition of oral hydralazine to conventional therapy. With conventional therapy, cardiac output increased from 3.4 +/- 0.8 (mean +/- 1 standard deviation) at rest to 4.7 +/- 1.4 liters/min during exercise. This increase in cardiac output on exercise during conventional therapy was mainly due to an increase in heart rate. After the addition of hydralazine, cardiac output at rest increased to 5.0 +/- 1.4 liters/min. The increase in cardiac output was essentially due to an increase in stroke volume. This enhanced stroke volume after hydralazine therapy was maintained during exercise. Hydralazine therapy did not change either the left ventricular filling pressure at rest or the magnitude of increase in left ventricular filling pressure during exercise. Nevertheless, increased cardiac output and stroke volume with similar changes in left ventricular filling pressure during exercise indicated improved left ventricular performance after hydralazine therapy. After short-term hydralazine therapy, symptom-limited peak exercise work load, duration of exercise and maximal oxygen consumption during exercise did not increase. Clinical follow-up at 2 months after long-term therapy revealed subjective improvement in exercise tolerance in 13 of the 14 patients.


Pharmacokinetics of digoxin in patients with acute myocardial infarction. The effects of acute myocardial infarction on the pharmacokinetics of digoxin were studied. Digoxin, 0.75 mg, was given orally to 12 patients with left-sided cardiac failure due to acute myocardial infarction and to 9 healthy control subjects. Serum concentration of digoxin in the first 4 hours and the area under the serum concentration-time curve in the first 12 hours after administration of the drug were lower in patients with infarction than in control subjects (P less than 0.01). The 24 hour area under the concentration curve, the amount excreted in urine and the renal clearance did not differ between the groups. The 24 hour area under the concentration curve correlated with the predigoxin pulmonary capillary wedge pressure and with heart rate (P less than 0.01). The decrease of renal clearance of digoxin was related to the serum activity of MB isoenzyme of creatine kinase (P less than 0.001). Morphine reduced and delayed the peak serum concentrations of digoxin (P less than 0.001). Thus, the absorption of oral digoxin was slower and the peak concentrations remained lower in patients with acute myocardial infarction than in healthy control subjects. However, the total amount of digoxin absorbed was unchanged.


Hemodynamic effects of intravenous metoprolol. The hemodynamic effects of the cardioselective beta adrenergic blocking agent metoprolol, at a dose of 0.1 mg/kg body weight administered intravenously, were studied in 10 patients undergoing routine cardiac catheterization. The beta adrenergic blocking effect of the drug was confirmed by a highly significant reduction (53 percent, P less than 0.001) in the mean heart rate response to a challenge with isoproterenol, and by a mean heart rate rssponse to a challenge with isoproterenol, and by a highly significant reduction (73 percent, P less than 0.001) in the isoproterenol-induced increase in the first derivative of left ventricular pressure (dP/dt). An intrinsic negative inotropic effect was shown by a 43 percent reduction (P less than 0.05) in the response of mean left ventricular dP/dt when the heart rate was fixed by atrial pacing alone. With the combination of atrial pacing and isoproterenol, metoprolol produced a 48 percent reduction (P less than 0.01) in the response of mean left ventricular dP/dt, resulting from both the intrinsic depressor effect and the beta adrenergic blocking effect on the rate-independent beta agonist activity of isoproterenol. There was no significant change in right atrial, femoral arterial or left ventricular end-diastolic pressure; analysis of left ventricular angiograms performed during atrial pacing before and after metoprolol revealed no significant effect on angiographic ejection fraction, pressure-volume loops or diastolic compliance. In two patients improvement in segmental wall motion was noted, and no deterioration was seen in any patient. Metoprolol is an effective cardioselective beta adrenergic blocking agent that, under these conditions, reduces catecholamine-induced increases in heart rate and left ventricular dP/dt without significant alteration in ejection fraction, preload or afterload.


Selective coronary arteriography in congenitally corrected transposition of the great arteries. Three cases of congenitally corrected transposition of the great arteries in adults who underwent selective coronary arteriography are presented. The morphologic features of the epicardial coronary anatomy are distinctive and are identifiable angiographically as morphologically right and left coronary arteries that are specifically concordant with the morphologically right and left ventricles. This relation is constant in the presented cases, in previously published coronary arteriograms of congenitally corrected transposition of the great arteries and in a review of the anatomic studies of congenitally corrected transposition of the great arteries that identify the coronary arterial pattern. Thus the angiographic characteristics of the epicardial coronary arterial pattern permit identification of the morphologic features of the underlying ventricle regardless of other spatial relations.


Two dimensional echocardiography in differentiating right atrial and tricuspid valve mass lesions. Atrial myxoma has been diagnosed on the basis of a characteristic M mode echocardiographic pattern of a mass of echoes appearing, with a lag phase, beneath the anterior leaflet of the mitral or tricuspid valve in diastole. However, this pattern is not specific for an atrial tumor. Two patients are described with tricuspid leaflet endocarditic vegetations whose M mode echocardiograms were strikingly similar to the M mode tracing from a patient with a large right atrial myxoma. In a fourth patient, artifact, resulting from the failure of lateral resolution of the atrial wall, was also capable of producing a mass of echoes appearing, with a lag phase, beneath the anterior tricuspid valve leaflet in diastole. In each patient, two dimensional echocardiography confirmed the presence or absence of a right-sided mass lesion and defined more precisely the location of the echocardiographic density relative to the right atrium and tricuspid valve. Because two dimensional echocardiography is capable of detecting anatomic relations in two distance dimensions and of visualizing movement of intracardiac structures relative to one another in real time, it can play an important role in the identification and differential diagnosis of intracardiac mass lesions.


Dependence of the effects of dietary cholesterol and experimental conditions on serum lipids in man. I. Effects of dietary cholesterol in a linoleic acid-rich diet. In this experiment the effect of dietary cholesterol in a linoleic acid-rich diet on serum cholesterol was tested. In a cross-over design 41 young healthy students received a linoleic acid-rich diet for 4 weeks at two levels of dietary cholesterol. The diet contained 14 to 15 energy% linoleic acid. The high cholesterol diet was obtained by adding two egg yolks a day to the rations. Supplementation of the linoleic acid-rich diet with the egg yolk cholesterol caused a significant rise of serum cholesterol of about 11 mg/100 ml (0.29 mmole/liter). The dietary cholesterol did not influence serum triglyceride levels. The influence on serum cholesterol was much less than expected, based on several predictive formulas. It is concluded that the presence of a high content of linoleic acid in the diet reduces the effect of dietary cholesterol on serum cholesterol if the cholesterol is provided as egg yolk.


Dependence of the effects of dietary cholesterol and experimental conditions on serum lipids in man. III. The effect on serum cholesterol of removal of eggs from the diet of free-living habitually egg-eating people. Forty-four healthy free living volunteers were used to study the effect of the removal of eggs from a habitual egg-rich diet. The subjects, recruited by advertising, normally consumed at least 1 egg per day. During the 3-week experimental period they were not allowed to eat any eggs or products containing large amounts of eggs, except cakes and tarts. Elimination of eggs from a habitual egg-rich diet did result in a small but significant decrease in serum cholesterol levels in all subjects. No correlation could be demonstrated between changes in serum cholesterol levels and the age of the subjects and between changes in serum cholesterol levels and the numbers of eggs eaten per week before the experimental period. A significant negative correlation was found between changes in serum cholesterol levels and the Quételet index for obesity and between changes in serum cholesterol levels and the serum cholesterol levels before the experimental period. The results indicate that a very variable response is present in a human population toward dietary cholesterol. More research seems to be necessary to describe and select the population of hyperresponders, the subjects who are more sensitive to changes in dietary cholesterol, and the hyporesponders. The results moreover indicate that effects of dietary changes in a free-living population are much smaller than can be accomplished in populations under controlled conditions.


Fatty acid composition of human adipose tissue from two anatomical sites in a biracial community. This report describes the age-race specific distribution of fatty acids in samples of adipose tissue taken from both the perirenal and buttock areas of 406 men autopsied in a community pathology study. This analysis of fatty acid composition of adipose tissue is part of a comprehensive investigation of atherosclerosis and coronary heart disease in a community setting. The findings from analysis of fatty acids are expressed as mass percentage of all fatty acids in adipose tissue triglyceride. For each age-site subgroup, white men tended to have higher mean percentages of myristic acid and palmitoleic acid than did black men. The converse was found for stearic acid. In the younger age groups only, the whites showed a higher mean percentage of linoleic acid than the blacks in adipose tissue from both sites. Age was associated with a decrease in mean percentage of stearic acid and an increase in mean percentage of oleic acid and palmitoleic acid in both races. The older age group had a lower mean percentage of linoleic acid than the younger age groups. The mean percentages of myristic, palmitic, and stearic acids were higher in perirenal tissue, while the mean percentages of palmitoleic and oleic acids were higher in buttock adipose tissue in both races.


Isocaloric exchange of dietary starch and sucrose in humans. II. Effect on fasting blood insulin, glucose, and glucagon and on insulin and glucose response to a sucrose load. Ten men and nine women ages 35 to 55 consumed two diets for 6 weeks each in a cross-over design. The diets were composed of identical natural foods and 30% of the calories as either sucrose or wheat starch. Carbohydrate, fat, and protein supplied 43, 42, and 15% of the calories, respectively. Of the calories 10% was eaten at breakfast (7:00 to 8:30 AM) and 90% at dinner (4:30 to 6:30 PM). Inital body weights were essentially maintained. Fasting serum insulin and glucose levels were significantly higher with the sucrose than with the starch diet. The insulin response and the insulin:glucose ratios after a sucrose load (2 g/kg body weight) were greater after the subjects consumed the sucrose diet. Sucrose feeding produced increases in fasting serum insulin, the insulin:glucose ratio and the insulin response to a sucrose load that were of greater magnitude in a subgroup of nine subjects classified as potentially carbohydrate-sensitive than in normal subjects. Glucose response to a sucrose load and fasting serum glucagon did not differ significantly with diet. Fasting insulin and glucose showed significant increases as a function of time on diet. These results indicate that sucrose feeding produces undersirable changes in several of the parameters associated with glucose tolerance.


Changes in content and composition of brain phospholipids in malnourished children. The content and composition of phospholipids were studied in the brain of children who died from severe malnutrition within the first 2 years of life, and compared with those obtained from well-nourished children who died of accidents, or of illnesses not known to affect the central nervous system. Each brain was separated into the constituent major parts--the forebrain, brain stem, and the cerebellum. With the exception of a few marasmic children under 1 year of age whose forebrain and cerebellum had higher phospholipid concentration than normal, the concentration of the lipids on dry weight basis in all brain regions of the malnourished children was the same, regardless of age, as that in the children who were normal nutritionally. However, the phospholipid:DNA ratio in the forebrain and the cerebellum of most of the malnourished children under 1 year of age was higher than normal. The brain stem of only a few malnourished children aged around 1 year also had higher phospholipid:DNA ratio than normal. Among the different phospholipids, sphingomyelin was found to be selectively decreased in each brain part of the malnourished children aged 1 year or more.


Penicillin pharmacokinetics in kwashiorkor. Intravenous penicillin kinetics have been studied in eight children with kwashiorkor on admission to hospital and when rehabilitated. A 75% increase in penicillin clearance was observed with recovery, associated with a fall in half-life; this was probably due to an improvement of both renal plasma flow and tubular function. The present observations and those of other authors working in this area are discussed and an approach to drug dosage of renally excreted drugs in kwashiorkor has been proposed.


Thiamin requirement of the adult human.

Thiamin requirement of the adult human. Young adult male subjects maintained on a metabolic ward were fed diets providing controlled intakes of thiamin and either 2800 or 3600 kcal. The higher level of calories was attained by an increased intake of carbohydrates. Constant weights were maintained by the subjects by adjusting daily activity and exercise schedules. Thiamin requirements were evaluated in terms of erythrocyte transketolase activity and urinary excretion of the vitamin. The results of the study revealed that a relationship exists between thiamin requirement and caloric intake and expenditure. Thus, when the calories being utilized were derived primarily from carbohydrate sources, the minimum adult male requirement for thiamin appeared to be 0.30 mg of thiamin per 1000 kcal. Urinary excretion of thiamin and erythrocyte transketolase activity appear to be reasonably reliable reflections of thiamin intakes and thiamin nutritional status. The use of these measurements in nutrition surveys appears justified. The microbiological assay (Lactobacillus viridescens) for measuring thiamin levels in urine samples appears to be a somewhat more sensitive but valid procedure as an alternate for the thiochrome method. Judged from the results of this study, the recommended intake for the adult human of 0.40 mg of thiamin per 1000 kcal by FAO/WHO and the recommended allowance of 0.5 mg per 1000 kcal by the Food and Nutrition Board of the NAS-NRC appear reasonable and amply allow for biological variations and other factors that may influence the requirement for this vitamin.


Vitamin B6 nutriture during pregnancy and lactation. I. Vitamin B6 intake, levels of the vitamin in biological fluids, and condition of the infant at birth. Vitamin B6 nutriture was assessed during pregnancy and lactation to determine possible relationships among vitamin B6 intake, levels of the vitamin in biological fluids and the condition of the infant at birth. Vitamin B6 levels were measured in maternal serum and in urine at 5 and 7 months gestation and at delivery, in cord serum and in milk at 3 and 14 days postpartum. Intake of vitamin B6, less than the Recommended Dietary Allowances (1974) for pregnancy and lactation, 2.5 mg/day, resulted in lower levels of the vitamin in maternal serum at delivery and in cord serum than higher intakes. Mothers whose infants had unsatisfactory Apgar scores at 1 min, (less than 7) had significantly low intakes of vitamin B6 and lower levels of the vitamin in both serum and milk than mothers whose infants had satisfactory scores, (greater than or equal to 7). At 5 months gestation, levels of vitamin B6 in maternal serum were significantly correlated with levels of the vitamin in cord serum and in milk at 14 days postpartum. This stage of gestation precedes the period of rapid growth of the central nervous system of the fetus, and is, therefore, a critical time for the assessment of maternal vitamin B6 nutriture.


Vitamin B6 nutriture during pregnancy and lactation. II. The effect of long-term use of oral contraceptives. Vitamin B6 nutriture was assessed during pregnancy and lactation to determine whether previous use of oral contraceptive agents (OCA) resulted in reduced reserves of the vitamin. Vitamin B6 levels were measured in maternal serum and urine at 5 and 7 months gestation and at delivery, in cord serum and in milk at 3 and 14 days postpartum. Long-term use of OCA (greater than 30 months) resulted in low levels of vitamin B6 in maternal serum at 5 months gestation and at delivery and in milk compared with values for short-term (1 to 30 months) and nonusers of OCA. Levels of vitamin B6 were also lower in the cord serum of long-term users of OCA as compared to nonusers.


Leukocyte hexose monophosphate shunt activity during phagocytosis in vitamin B12 and folic acid deficiencies. Little information exists about leukocytic function in megaloblastic anemia. A report of abnormal hexose monophosphate shunt and phagocytic activity only in vitamin B12 deficiency and not in folate deficiency prompted us to examine latex-stimulated hexose monophosphate shunt activity in the two conditions. Only two of our five patients with pernicious anemia demonstrated defective activation, while one of the two folate-deficient patients also had this defect. These findings clearly indicate that hexose monophosphate shunt activity is neither consistently impaired in vitamin B12 deficiency nor consistently unaffected in folate deficiency.


Relationship between age and vitamin E level in epileptic and normal children. Plasma vitamin E was assayed in 100 children on anticonvulsants either singly or in combination. Their plasma vitamin E levels were lower than in 100 apparently normal children. The age range of the children was between 2 and 12 years. The plasma vitamin E levels of the control children were lower than published values for adults. In the normal course of development, vitamin E levels increase with age but this developmental pattern does not occur in groups of epileptic children, and this may be related to the metabolic effects of drug therapy in epilepsy.


Nutritional manipulations and tumor growth. I. The effects of starvation. The effects of starvation on tumor and host growth were studied in growing male Fischer rats bearing methylcholanthrene-induced sarcomas. Tumor growth was evaluated by changes in weight, volume, and incorporation of tritiated methyl thymidine into tumor DNA, (dpm/microgram DNA). Host growth was followed by changes in total body weight, carcass weight, and dpm/microgram liver DNA. All periods of starvation (24 to 96 hr) caused significant decreases in host body and carcass weight and dpm/microgram liver DNA. Changes in tumor weight and tumor volume in fed and starved animals were equal. Tumor dpm/microgram DNA in starved animals increased (P less than 0.005) relative to fed controls at 48, 72, and 96 hr starvation intervals. Starvation allows continued tumor growth while host wasting occurs, and is accompanied by increased tumor dpm/microgram DNA in this system.


Relationship between hemoglobin concentration and transferrin saturation in iron-sufficient infants. Ten groups of healthy infants and children from 2 months to 15 years of age were studied, each consisting of 98 to 238 subjects. In young infants whose serum ferritin values indicated ample storage iron, the concentration of hemoglobin was found to bear a significant relationship to the degree of iron saturation of transferrin. This phenomenon was evident throughout the range of transferrin saturation until 1 year of age but became undetectable or less significant from 2 to 15 years of age. We postulate that the production of hemoglobin could be influenced through a broader range of transferrin saturation in rapidly growing infants than in the older child or adult.


Longitudinal changes in the mineral content of human milk. Thirty-eight lactating women, from 1 to 31 months postpartum, provided monthly milk samples for determination of calcium, magnesium, manganese, copper, iron, and zinc. Subjects remained in the study an average of 4 consecutive months, with a maximum participation of 9 months. Subject variation accounted for the majority of variance in the raw data. After statistically controlling subject effect, copper, iron, and zinc levels were shown to be significantly related to duration of lactation. Prediction equations for these three minerals were developed, making it possible to calculate, on an individual basis, the copper, iron, and zinc levels of milk to be produced in future months. Data were also collected to determine possible correlations between breast milk mineral levels and the maternal dietary intake, serum levels, or hair concentration of these same minerals. No significant correlation was found between the milk mineral content and any of the three parameters under study.


Effect of fiber from fruits and vegetables on metabolic responses of human subjects. III. Zinc, copper, and phosphorus balances. Intakes and excretions of zinc, copper, and phosphorus were determined for 12 men when they consumed a diet low in fiber and when they consumed a diet containing fiber from fruits and vegetables (high-fiber diet). All subjects consumed both diets for 26 days each. The low-fiber diet was supplemented with copper so that it was equivalent to the high-fiber diet in this respect. Mean daily intakes on the low- and high-fiber diets, respectively, were: zinc, 13.2 and 12.6 mg; copper, 1.8 and 1.6 mg; phosphorus, 1.639 and 1.690 g. Mean daily balances on the low- and high-fiber diets, respectively, were: zinc, +3.5 and -0.9 mg; copper, +0.2 and -0.4 mg; phosphorus, +0.361 and +0.292 g. Zinc and copper balances differed significantly on the two diets (P less than 0.001 and P less than 0.005, respectively, but phosphorus balances did not. The fiber supplied by the fruits and vegetables contained more lignin and cellulose and less hemicellulose than would an equivalent amount of fiber from bran. The bran would supply more magnesium, zinc, and copper than this particular diet containing fruits and vegetables.


High-carbohydrate, high-fiber diets for insulin-treated men with diabetes mellitus. The effects of high-carbohydrate, high plant fiber (HCF) diets on glucose and lipid metabolism of 20 lean men receiving insulin therapy for diabetes mellitus were evaluated on a metabolic ward. All men received control diets for an average of 7 days followed by HCF diets for an average of 16 days. Diets were designed to be weight-maintaining and there were no significant alterations in body weight. The daily dose of insulin was lower for each patient on the HCF diet than on the control diet. The average insulin dose was reduced from 26 +/- 3 units/day (mean +/- SEM) on the control diets to 11 +/- 3 (P less than 0.001) on the HCF diets. On the HCF diets, insulin therapy could be discontinued in nine patients receiving 15 to 20 units/day and in two patients receiving 32 units/day. Fasting and 3-hr postprandial plasma glucose values were lower in most patients on the HCF diets than on the control diets despite lower insulin doses. Serum cholesterol values dropped from 206 +/- 10 mg/dl on the control diets to 147 +/- 5 (P less than 0.001) on the HCF diet; average fasting serum triglyceride values were not significantly altered on the HCF diets. These studies suggest that HCF diets may be the dietary therapy of choice for certain patients with the maturity-onset type of diabetes.


Comparison of anthropometric measures of nutritional status in preschool children in five developing countries. Weight, height, and arm circumference were measured in 7304 children 1 to 5 years old in Columbia, Costa Rica, the Dominican Republic, India, and Pakistan. Previously developed indices using these measures were applied to assess nutritional status, and the agreement between measures was compared. Weight for age and height for age deficits increased with age while weight for height deficits diminished. Many children diagnosed as mildly malnourished by weight for age were found to have normal weights for their actual heights. Deviations from weight for age norms were frequently due to height limitations. Highest positive correlation was found between weight and height, and between weight for age and height for age. Good agreement in malnutrition diagnoses was found between a weight for height limit of 90% of standard and a weight for age limit of 75% of standard. A cut-off point of 80% of standard weight for height was too low to detect most malnourished children. An age-constant arm circumference limit of 13.5 cm identified nearly all children with severe or acute malnutrition by weight for age or weight for height.


Folacin and iron status and hematological findings in predominately black elderly persons from urban low-income households. The folacin and iron status and hemotological parameters of 193 persons 60 years of age and older from urban low-income households were evaluated. Of the serum folacin values 30% were between 3 and 6 ng/ml and 8% were below 3 ng/ml. Of these subjects 60% could be classified as "high risk" (less than 140 ng/ml) and 11% as "medium risk" (140 to 160 ng/ml) based on red blood cell folacin concentrations. Serum iron was normal (greater than 50 micrograms/dl) for all subjects as was transferrin saturation (greater than 15%). Hematological indices showed a 14% incidence of anemia (hemaglobin less than 12 g/dl), and 32% incidence of leukopenia (leukocytes less than 4.8 X 10(3)). These findings demonstrate widespread folacin deficiency and no evidence of iron deficiency in these elderly people.


A method for the detection and assay of iron stable isotope tracers in blood serum. Methodology for use of stable isotopes of iron (54Fe, 57Fe, and 58Fe) as biological tracers was developed. Tracers were quantitated by measurement of ion abundances with a quadrupole mass spectrometer. The volatility of the iron was enhanced by chelation with 2,4-pentanedione prior to analysis. Samples were introduced into the mass spectrometer via a direct inlet probe. Ion abundance ratios were calculated from integrated ion current measurements obtained for selected ions in the two-ligand fragment of the chelate. Stable isotope tracer concentrations were calculated from these ratios. A prodecure was developed for the formation and purification of serum iron chelates. The method was used to analyze iron standards and blood serum samples containing known amounts of added 58Fe. The disappearance from pony serum of injected 58Fe was used as an in vivo test of the method. It was estimated that a minimum of 1.5 mg of either 54Fe, 57Fe, or 58Fe would be required to label 1 g of natural iron at detectable levels. The methods has promise as an alternative to radioisotope tracer techniques for some applications involving human subjects.


Nutritive value of brown and black beans for infants and small children. A precooked, instantized mixture of brown and black beans, with and without 0.3% DL-methione added, served as the only source of protein in the diets of 10 recovered malnourished infants and children 10 to 42 months of age. At 6.4 to 5.7% dietary protein calories stool wet weights were twice as high, apparent N absorption significantly lower (65.6 +/- 5.9 versus 87.5 +/- 2.3% of intake), and apparent N retention much lower (9.8 +/- 6.1 versus 34.5 +/- 10.2% of intake) than during preceding and following isocaloric and isonitrogenous casein-based diets. The addition of methionine resulted in minimal improvement in N retention and a highly suggestive increase in fasting plasma free methionine. Prolonged feeding of the methionine-enriched beans at 8.0 to 10.9% protein calories supported satisfactory growth and serum albumin levels in two of three children, not so in the smallest one, in whom repeated balance studies demonstrated no decrease over time in stool wet weight and on marginal improvement in N absorption and retention. The poor digestibility of the protein in these beans is the first-limiting factor in its utilization by infants and small children.


Nuclear DNA and histologic studies of genital lesions in diethylstilbestrol-exposed progeny. II. Intraepithelial glandular abnormalities. This study has analyzed the nuclear DNA content of intraepithelial glandular lesions in diethylstilbestrol (DES)-exposed offspring. The endocervical cells and endometrial-tubal cells present in the vaginal adenosis and pericervical collars had a euploid distribution. However, greater proliferative activity was found among the endometrial-tubal cells. In the cells of vaginal adenosis of a postpartum woman without a confirmed history of maternal exposure to DES, a polyploid pattern was found, indicating that endometrial-tubal cells underwent hyperplastic changes under the influence of hormonal stimulation. In an atypical adenosis derived from endometrial-tubal cells, an aneuploid pattern was found. Based on these findings, it is suggested that endometrial-tubal cells have a greater proliferative potential than endocervical cells.


Myxoid liposarcoma. An ultrastructural study of two cases. Two cases in which myxoid liposarcomas were examined by use of light and electron microscopy are presented. The relationship of this tumor to the development of normal adipose tissue is discussed. Most of the ultrastructural features were identical to those of developing white adipose tissue. Features not typical of developing white adipose tissue, such as congeries of 60-Angstrom filaments and large masses of glycogen, are also illustrated and discussed.


Epithelial foot-process effacement in patients with proteinuria. In an effort to determine the pattern of foot-process effacement or "fusion" in proteinuria, quantitative measurements were performed on human tissue from patients with urinary protein excretion exceeding 0.5 g/d. Serial electronmicrographs were analyzed and the results related to both quantitative urinary protein and underlying disease. Although foot-process effacement was widespread, it was never universal. Some portions of glomeruli were morphologically normal in every case. The proportion of effaced foot processes did not vary directly with the level of urinary protein. With the possible exception of focal glomerulosclerosis, the primary disease did not appear to influence the amount of effacement.


Flow cytofluorimetry in routine diagnostic cytology. A pilot study. A simple procedure for disrupting cell clumps may aid in the automation of gynecologic cytology by flow cytofluorimetry. Such a procedure, using enzymatic digestion and fluorescent staining, was applied to aliquots of 264 gynecologic exfoliative specimens. Results were compared with cytopathologic diagnoses. A fluorimetric criterion of hypertetraploidy was used to detect abnormality. One quarter of the specimens fulfilled this criterion, including 15 of 17 specimens rated cytologically as premalignant. Two thirds of the falsely abnormal results were attributable to aggregated microorganisms, glandular clumps, and pusbound clumps.


Evaluation of a pectin agar medium for isolation of Yersinia enterocolitica within 48 hours. A modified pectin agar medium was evaluated for the rapid isolation and presumptive identification of Yersinia enterocolitica. Of 118 isolates of Enterobacteriaceae tested, only the 13Y. enterocolitica and the three Klebsiella oxytoca strains produced colonies that depressed and sank into the agar. Yersinia enterocolitica was also easily identified in mixed cultures, even from inocula containing three times as many other Enterobacteriaceae organisms as Y. enterocolitica. The recovery of Y. enterocolitica was evaluated on Mueller-Hinton, pectin, Hektoen enteric, xylose lysine desoxycholate, Salmonella-Shigella, and MacConkey agars. Compared with Mueller-Hinton agar, the pectin agar showed a 100% recovery of Y. enterocolitica, with all strains having depressed colonies, while the other media showed lesser recoveries of only 5 to 25%, with no other discriminating colonial characteristic.


Quality control of the latex-fixation test. Standardization of the latex-fixation test for the detection of rheumatoid factor may be achieved by the preparation of a standard reference serum. A number of guidelines for the quality control of precision and sensitivity of the test are suggested. In the use of dilution procedures, a 0.1 log10 or a 0.05 log10 difference between tubes is employed. The end point is defined and titer expressed in terms of a final dilution represented by the amount of antigen-antibody added. For statistical purposes all serologic data are geometrically expressed. Commercial kits may be standardized in terms of minimum detectable units and normalized for titer and unit values to enable laboratories to compare results.


Performance of latex-fixation kits used for serologic diagnosis of rheumatoid factor in rheumatoid arthritis sera. Ten latex-fixation kits (both slide and tube) were evaluated by use of a reference serum containing 250 IU of rheumatoid factor (Communicable Disease Center). All tests were performed with serial dilution of serum; adjacent tubes differed by a factor of 0.10 log10. Geometric titers, means, standard deviations, and variance analysis were used to evaluate commercial kits. Three levels of variance were applied: (1) 0.18 or less for intralaboratory variation when the same serum is tested with the same kit; (2) 0.18-0.35 when various lots or batches of the same serum were used; (3) 1.0 or less when various commercial kits were tested with the same serum. The sensitivity of each commercial kit was determined by assigning to it a value (the minimum detectable unit) arrived at by dividing the number of units in the standard by the titer obtained. The technic presented could be applicable to other serologic tests, and thus provide a general method for their standardization and quality control.


An improved microchromatographic procedure for separating HbA2 from HbS for the purpose of quantitation. A microchromatographic method for separating hemoglobin A2 from hemoglobin S and their subsequent quantitation on DEAE-cellulose has been improved. The new procedure is more versatile, since the same system can be used when hemoglobin S is present or absent in the sample without changing to a longer column or another buffer system. Also, the technic is less sensitive to small changes in pH of buffers or resin than are other procedures.


Pitfalls in the interpretation of leukocyte counts of newborn infants. Some pitfalls in the interpretation of neonatal leukocyte counts are identified. The well-known variability in neonatal leukocyte counts was investigated by simultaneously sampling arterial, venous and capillary blood, and during periods of rest and mild and violent exercise. Venous blood leukocyte counts were 82% +/- 3.5 (mean +/- SE, P = less than .001) of counts in simultaneously drawn capillary blood from heel punctures; arterial blood counts were 77% +/- 5.3 (P less than .001) of capillary blood values. Following violent crying, capillary blood leukocyte counts increased to 146% +/- 6.1 (P less than .001) of baseline values, and a shift to the left occurred. Milder exercise induced an increase to 113% +/- 5.2 (P less than .05), without a leftward shift. Thus, counts from different vascular sources cannot be considered equivalent. Also, counts from vigorously crying babies may show leukocytosis and a leftward shift, and erroneously suggest bacterial infection. It is recommended that serial counts be obtained from a consistent vascular source in resting babies.


Opportunistic fungal infection among cancer patients. A ten-year autopsy study. A high incidence of opportunistic fungal infections among cancer patients has been a pressing problem confronting clinicians. The fungal infections in 3,278 consecutive autopsies at Thomas Jefferson University Hospital during a ten-year period (1966-1975) were studied. There were 1,204 (36.7%) cancer patients; 85 (7.1%) of these patients had concomitant fungal infections. The incidence was 9.3% during the last five-year period; 5.1% during the first five-year period. Candidiasis was the most frequent fungal infection (52.2%) among these patients, followed by aspergillosis (31.1%), mucormycosis, cryptococcosis, histoplasmosis and nocardiosis. The leukemias and lymphomas were the most frequent malignancies associated with fungal infections. However, in this study, unlike others, the incidences of fungal infection in patients with some solid tumors were also high, especially those in patients with cancers of the colon and pancreas.


An evaluation of two methods of laboratory quality control. Two methods for quality control of automated blood counters have been compared: (1) monitoring results from patients' samples, and (2) analysis of results of a stable whole-blood control. The latter method proved better able to distinguish calibration changes from patient variation.


Propylene glycol as a cause of an elevated serum osmolality. Two severely burned patients experienced the onset of marked hyperosmolality during topical treatment with a cream containing silver sulfadiazine as an antimicrobial agent. Serum samples from both patients were studied for the presence of substances absorbed from the vehicle of the cream. Prophylene glycol, in concentrations which were high enough to account for the difference between calculated and measured osmolality, was demonstrated in the sera of these patients by gas chromatography.


Actinomycotic pulmonary abscess in an immunosuppressed patient. The clinical history of a patient with rheumatoid arthritis and bacteriologic findings from a pulmonary abscess occurring during prednisone therapy are presented. Direct transthoracic aspiration of the lesion yielded a pure culture of Actinomyces odontolyticus. This is believed to be the first case of a deep visceral infection with this organism, an inhabitant of the normal mouth and gums. Immunosuppression of the host probably played a role in establishment of the infection.


Micronema deletrix meningoencephalitis in an adult man. This is apparently the second report of a case of human meningoencephalitis caused by the nematode Micronema deletrix. The patient had severe granulomatous meningoencephalitis with numerous foci of hemorrhage and encephalomalacia. Numerous adult female and larval M. deletrix were in the brain. The organisms probably inhabit decaying organic material, but occasionally parasitize the kidney, nose, or central nervous system of the horse. In its parasitic form the nematode replicates parthenogenetically.


The biology of the HL-A system and the association with malignant lymphomas. Present knowledge of the HL-A system as it relates to lymphoproliferative disease is reviewed briefly. Preliminary results from a current study demonstrate an elevated frequency of Aw33 and depressed frequency of B17 associated with non-Hodgkin's lymphoma-leukemia. In somewhat weaker association, Aw24 and Aw33 are elevated in follicular-center-cell lymphomas, while Bw44 is depressed. It is concluded that more specific subclassification of the lymphomas according to immunologic concepts may aid in correlating the disease with HL-A type as it has for Hodgkin's disease.


Kinetic studies of cells in childhood leukemias. A review of cell kinetic studies in acute childhood leukemia with a comparison of leukemic transformation of non-Hodgkin's lymphoma is presented in this paper. Leukemic cell populations have a longer cell cycle than their normal cell counterparts. The cell populations are comprised of proliferating and resting fractions and are capable of self-maintaining growth. Growth regulation is determined primarily by the size of the proliferating cell population or growth fraction. The growth fraction can vary as to site of disease, the clinical phase, following chemotherapeutic perturbation, and most importantly is related to the specific tumor cell type. Within a specific type of leukemia there is considerable variability of proliferative activity at time of diagnosis, but this variability bears no relationship to the subsequent clinical course. Those leukemias, such as the E rosette-positive form of lymphocytic leukemia characterized by rapid tumor growth and large tumor bulk, are also associated with tumor cell populations having larger growth fractions than standard lymphocytic leukemia. There is evidence for growth regulation of leukemic cell populations on systemic, regional, and, perhaps most importantly of all, intrinsic cell levels. It is this area of growth regulation for these tumor cell populations which currently needs the greatest research attention.


A dynamic interpretation of multiparameter studies in the lymphomas. A general approach to the analysis of cellular life cycle traverse patterns is described. This approach is exemplified in human lymphomas, using Coulter volume and DNA content measurements obtained by flow cytometry. Among the B-cell tumors the large-cell lymphomas generally show larger fractions of DNA-synthesizing cells and a higher degree of proliferative activity than the small B-cell lymphomas. Paired cell-by-cell measurements of Coulter volume and DNA content can be used to distinguish large aneuploid tumor cells from smaller diploid cells in mixed cell populations. The paired measurements can also be used to explore the kinetic properties of subpopulations within individual tumor samples. It can be shown that within individual lymphoma samples there are subpopulations of large cells that have greater proliferative activity than the small cells.


The Primary Mental Health Project (PMHP): evaluation of current program effectiveness. This study evaluated the effectiveness of the Primary Mental Project (PMHP), a program for early detection and prevention of school adjustment problems. Pre- and postprogram assessments were done with 215 primary-grade children seen in PMHP, usig teacher ratings of problem behaviors and competencies, and child-aide ratings of problems. School mental health professionals judged educational and behavioral changes in project children during the year. Significant across-the board improvements were found on all criterion measures. Modest intercorrelations among criterion change estimates suggested that the observed changes were due to program, rather than halo, effects. PMHP children also improved significantly more than matched, retrospective controls.


Unexpected consequences of deinstitutionalization of the mentally disabled elderly. An unexpected consequence of the rapid deinstitutionalization of state mental hospital patients has been a sharp rise in posttransfer mortality among the elderly. Considerable evidence suggests that outcome is mediated by two factors. Elderly patients with certain characteristics - especially physical frailty and severe cognitive impairement - comprise a high-risk subgroup for whom relocation is likely to be fatal. Among other elderly persons, environmental, personality and personality-environment congruence are associated with posttransfer prognosis. The studies reviewed indicate that the therapeutic value of deinstitutionalization for mentally disabled elderly persons is problematic.