Response of plasma histaminase activity to heparin in normal subjects and in patients with small cell carcinoma of the lung.

Plasma histaminase (PH) activity only partially reflected the consistently high activity of histaminase in tumor tissue of patients with small cell carcinoma of the lung (SCC). To determine whether heparin might release histaminase from tumor tissue into the circulation as it does from some normal tissues, we studied the response of PH activity to small doses of heparin in 41 patients with SCC and in 57 normal subjects. In patients with SCC, the initial mean PH activity (2.0 U/m) was not different from that in normal subjects (1.7 U/ml). After heparin administration, the mean PH activity was no different between the 2 groups (patients with SCC, 3.1 U/ml; normal subjects, 3.5 U/ml). In both groups, the higher the initial PH activity, the greater the magnitude of the PH activity response to heparin. This relationship was linear (normal subjects, r = 0.88; patients with SCC, r = 0.91). However, in patients with SCC, the increase in post-heparin PH activity, as related to the basal levels, was significantly less than that in normal subjects (P less than 0.001 by analysis of covariance). The data suggested that heparin did not affect the release of histaminase from tumor tissue into plasma to the same degree as it promoted the enzyme's entry from normal tissue sources. The differences between the groups may enable us to differentiate between selected patients with SCC and normal subjects with borderline high PH activity values.

Silent ischemia predicts infarction and death during 2 year follow-up of unstable angina.

Silent myocardial ischemia as detected on Holter electrocardiographic (ECG) monitoring is present in greater than 50% of patients with unstable angina despite intensive medical therapy. The presence and the extent of silent ischemia have been correlated with an increased risk of early (1 month) unfavorable outcome including myocardial infarction and need for coronary revascularization for persistent symptoms. Seventy patients with unstable angina who had undergone continuous ECG monitoring for silent ischemia were followed up for 2 years; 37 patients (Group I) had Holter ECG evidence of silent ischemia at bed rest in the coronary care unit during medical treatment with nitrates, beta-receptor blockers and calcium channel antagonists; the other 33 patients (Group II) had no ischemic ST segment changes (symptomatic or silent) on Holter monitoring. Over a 2 year follow-up period, myocardial infarction occurred in 10 patients in Group I (in 2 it was fatal) compared with one nonfatal infarction in Group II (p less than 0.01 by Kaplan-Meier analysis); revascularization with either coronary bypass surgery or angioplasty for symptomatic ischemia was performed in 11 Group I and 5 Group II patients (p less than 0.05). Multivariate Cox's hazard analysis demonstrated that the presence of silent ischemia was the best predictor of 2 year outcome. Therefore, persistent silent myocardial ischemia despite medical therapy in patients with unstable angina carries adverse prognostic implications that persist over a 2 year period.

Histologic predictors of acute cardiac rejection in human endomyocardial biopsies: a multivariate analysis.

To identify specific histologic abnormalities that could predict early cardiac rejection before the development of myocyte necrosis, 167 consecutive endomyocardial biopsy samples from 18 cardiac transplant recipients were retrospectively analyzed and 17 histologic variables were semiquantitatively graded from 0 to 3. Forty-five biopsy samples contained foci of myocyte necrosis and were labeled Rejectors. The two samples immediately preceding Rejector biopsies were labeled Predictors (n = 44). All remaining samples were labeled Others (n = 78). Endocardial and interstitial infiltrates, interstitial mononuclear cells, pyroninophilic mononuclear cells, polymorphonuclear leukocytes and other cells (eosinophils and plasma cells) were significantly increased in graded severity in Rejector biopsy samples as compared with Predictors or Others (p less than 0.001, ANOVA testing). These variables cannot distinguish Predictor biopsy specimens from Others. On the other hand, interstitial edema, perivascular karyorrhexis and perivascular infiltrate with intermyocyte extension are histologic abnormalities that can distinguish Predictor biopsy samples from Others (p less than 0.001, ANOVA testing). Multiple logistic regression analysis indicates that the relative risk of developing myocyte necrosis when a biopsy sample contains interstitial edema is 8.1. With perivascular infiltrate with intermyocyte extension in addition, the relative risk is 41.4. In summary, three histologic abnormalities have been identified that help predict the future development of myocyte necrosis within the next two endomyocardial biopsies. Biopsy specimens with these abnormalities probably represent early cardiac rejection before the development of myocyte necrosis.

Acute nifedipine withdrawal: consequences of preoperative and late cessation of therapy in patients with prior unstable angina.

Reports of acute ischemic events after withdrawal of calcium antagonist therapy in outpatients and during bypass surgery in patients with prior angina at rest prompted the examination of the effect of nifedipine withdrawal in 81 patients who had completed a prospective, double-blind randomized trial of nifedipine versus placebo for rest angina. Thirty-nine patients underwent bypass surgery for uncontrolled angina or left main coronary artery disease. No significant difference between patients withdrawn from nifedipine or placebo was seen in the incidence of perioperative myocardial infarction, hypotension requiring intraaortic balloon counterpulsation, vasopressor or vasodilator requirements or incidence of significant arrhythmias. An additional 42 patients had completed 2 years on a protocol consisting of nitrates and propranolol in addition to nifedipine or placebo. During a mean of 66 hours of continuous monitoring after withdrawal of nifedipine or placebo, heart rate and blood pressure were unchanged. A worsening of previously present angina at rest occurred in five patients who had continued to experience rest angina before drug withdrawal, four of whom were withdrawn from nifedipine. No patient with class I to III angina experienced new onset of rest angina during drug withdrawal. No patient experienced myocardial infarction. There was no significant difference between patients withdrawn from nifedipine or placebo in the duration or frequency of ischemic ST changes on continuous electrocardiographic monitoring, or in duration or positive results of serial exercise treadmill testing. Thus, no early adverse effects of acute nifedipine withdrawal were found in patients with prior rest angina at the time of bypass surgery or in stable patients receiving long-term medical therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic cardiac catheterization variables in survivors of acute myocardial infarction: a five year prospective study.

The prognostic variables from predischarge coronary angiography and left ventriculography in survivors of acute myocardial infarction during the years 1974 to 1978 were evaluated in 143 patients (less than or equal to 66 years of age) with documented myocardial infarction who were then followed up prospectively for 5 years. One half of the study population had triple vessel coronary disease (greater than or equal to 50% stenosis). However, only 7% of patients had severely depressed left ventricular function with an ejection fraction less than or equal to 29%. Evaluation of the contribution of many clinical and angiographic variables to a first cardiac event (death, nonfatal reinfarction or coronary artery bypass surgery) was considered with Kaplan-Meier actuarial curves and multivariate Cox's hazard function analysis. A risk segment was defined as an area of contracting myocardium supplied by a coronary artery with a greater than 50% stenosis. Multivariate analysis demonstrated that right plus left anterior descending coronary artery stenoses (p less than 0.01), ejection fraction (p less than 0.01) and the presence of risk segments (p less than 0.05) were significant predictors of outcome. Furthermore, on separate multivariate analyses, the angiographic variables added significantly to the clinical variables to predict cardiac events over 5 years of follow-up. Therefore, in survivors of acute myocardial infarction who undergo cardiac catheterization, additive prognostic information is obtained that can be used to stratify risk over 5 years.

Interstitial pneumonitis after allogeneic bone marrow transplantation. Nine-year experience at a single institution.

Of 386 patients with allogeneic bone marrow transplants (BMT) treated during a 9-year interval, 166 developed interstitial pneumonitis (IP). Idiopathic and cytomegalovirus (CMV) IP constituted 90% of the 113 cases in which tissue was examined. Risk factors for IP overall were acute graft-versus-host disease (AGVHD), remote transplant date, the diagnosis of leukemia, and GVHD prophylaxis with agents other than cyclosporine. Risk factors for CMV IP were pre-transplant CMV seropositivity, CMV excretion, age greater than 10 years, AGVHD, GVHD prophylaxis with agents other than cyclosporine, and a remote transplant date. Patients transplanted for aplastic anemia were at lower risk for idiopathic IP than those transplanted for leukemia. The incidence of IP in patients given busulfan plus cyclophosphamide was equivalent to that in patients receiving cyclophosphamide plus total body irradiation. The incidence of idiopathic IP remained constant over this 9-year period while CMV IP declined significantly.

Determinants of growth among poor children: effect of expenditure for food on nutrient sources.

The effect of increasing expenditure on the nature and the amounts of foods consumed by children from an urban population was estimated by studying the diets of 111 children from 20 typically poor families and those of 12 children from six economically better off families who had a much more satisfactory growth status. Total calories and protein, fat, and carbohydrate calories were expressed as a fraction of each individual's estimated energy requirement, thus adjusting for sex, age, and size. No important sex differences were found. Calorie intake was 87.2 +/- 17.3% and 111.4 +/- 18.1% of requirement for the two groups, respectively. Differences were found between the groups in protein calories which were totally due to milk and meat. Differences in fat calories were due to milk, meat, and separated fats. There was no significant difference between groups in total carbohydrate calories, although there were shifts in its components with increasing expenditure. Regression analysis of calorie adequacies as a function of per capita expenditure for food, both in the poorer group and in the combined population, were performed and yielded highly significant (p less than 0.001) results. These were due to significant gradual increases in the consumption of milk, meat, separated fats, fruits and vegetables on top of an almost constant consumption of the staple cereals, roots and tubers.

Urban-rural differences in the growth of Peruvian children.

The growth characteristics of children from four villages in northern Peru were compared with those of poor urban children in the capital city, in whom short stature but generally satisfactory weight for height relationships after infancy had been demonstrated. Height for age and weight for age fell more rapidly during infancy in the rural than in the urban children of both sexes. Rural girls caught up with the urban girls in height during childhood but did not match them in weight until late adolescence. Their weight to height ratios were consistently lower after 1 year of age, most strikingly between 2 and 5 years of age, and did not approach or match those of the urban girls until adolescence. Rural boys did not catch up with the urban boys in height or weight (differences in height were not statistically significant between 6 and 10 years, however) and their ratios remained consistently lower until late adolescence, most strikingly in early childhood and during puberty. Such urban-rural and sex differences, if typical and current, might well call for very different remedial measures at different ages in each of the populations.

Growth standards for poor urban children in nutrition studies.

In order to estimate the importance of a variety of environmental and dietary factors as determinants of growth in a group of 123 poor Peruvian urban children between 2 and 19 years old, we found it necessary to express anthropometric measurements in units that were not age- or sex-dependent. Height quotient and weight quotient for each child were calculated from height and weight ages derived from the 50th percentile of the Boston reference data for the appropriate sex. Only 5% of the children had heights above the Boston 50th percentile (height quotient greater than 100) and 18% had weights above the 50th percentile (weight quotient greater than 100), but 88% had weights that were appropriate or excessive for height (weight/height quotient greater than or equal to 1.00). Some CATch-up" gains in relative height and weight were apparent in preschool children but more impressive gains in both linear and ponderal growth, relative to the Boston data, were evident between 8 and 13.5 years in girls and 10 and 17 years in boys. When the same quotients were calculated for a much larger sample from the same socioceonomic level it seemed likely that this last peak was due to earlier puberty and sexual maturation, and that quotients derived from the Boston data would have different meanings at different ages, making them inappropriate for further statistical analysis. New quotients for the study population, derived from the larger Peruvian group, did not have sex- or age-dependent trends. Racial and regional differences in patterns of growth must be taken into account in the interpretation of anthropometric and nutritional data.

Blood glucose rise after lactose tolerance testing in infants.

Lactose tolerance tests are used clinically to screen children and infants. It is assumed that absorption of a lactose challenge in infants would occur in a predictable pattern prior to weaning. Twenty-one infants from 3 to 12 months of age were studied. The maximum blood glucose rise over fasting levels ranged from 11.0 to 62.0 mg/100 ml; the mean was 32.6 mg/100 ml. Six infants had a maximum rise of less than 20 mg/100 ml. Eleven infants (52%) had a maximum rise of greater than 30 mg/100 ml. Signs of intolerance were not noted in any subject. Weight and length were normally disturbed. Results indicate the variance in glucose rise existing within a population of infants growing normally and consuming milk. Gastric emptying, digestion, and absorption may influence the blood glucose rise after a lactose test. Established glucose levels used as an index to lactose absorption in older children and adults may not accurately reflect lactase activity in infants.

Determinants of growth among poor children: nutrient intake-achieved growth relationships.

Seven-day individual weighed dietary intakes and anthropometric measurements were determined in 123 children, 2 to 19 yr of age, from 26 poor families in Lima: each included one child who had been malnourished, six were adopting families. Heights and weights were converted to "ages" based on Boston reference data and local data, then to "quotients" as percentages of actual ages. Mineral and vitamin intakes were expressed as amounts per day and per 1000 kcal, calories and protein as percentages of FAO/WHO recommendations for age and height age and of modified recommendations based on size of Peruvian children. Regression analyses identified common sources of nutrients and greater dependence of intakes on body size than on age. Analysis of covariance for sex identified different nutrient-growth correlations. Polynomial regression analysis identified percentage protein from animal sources and percentage fat calories as having significant quadratic as well as linear correlations with achieved growth. In males, multiple regression analysis identified percentage protein from animal sources and beta-carotene intakes as strongly associated with achieved height and weight, and percentage fat calories as strongly associated with weight quotient/height quotient ratios. In females the correlations were not as strong, possibly because a significant percentage had reached the menarche some time before the survey and were probably no longer growing. Nevertheless, calorie intake, as a percentage of the recommendation for height age, was prominent in the regressions for height quotient and percentage fat calories in that for weight quotient. The very strong association of animal protein intake with male height, despite seemingly generous total protein intakes, is difficult to reconcile with current recommendations. The possible role of vitamin A (as beta-carotene) has potentially important implications for food policies.

Determinants of growth among poor children: relation of nutrient intakes to expenditure for food.

The growth status and the nutrient intakes of 123 children from 26 urban poor families in Peru were related to per capita expenditure for food. Children from six better off families were taller and heavier (p less than 0.001), with no difference in weight for height. They had significantly higher calorie and total protein intakes (as percentage of recommended) and higher intakes of animal protein, fat, calcium, carotene, riboflavin, and vitamin C. When macronutrient intakes were expressed as percentages of recommended calorie intakes, correcting for age and relative size, all of the increase in total protein intake was due to animal protein, vegetable protein remaining constant. Almost all of the increase in adequacy of total calories was due to increasing fat intakes, relatively much less to carbohydrate, and this only among the poor families. In this population, as more money becomes available to purchase food, there is an increase in animal protein and fat intakes, over an almost constant vegetable protein and carbohydrate intake. There is a simultaneous increase in consumption of fruits and vegetables, accounting for increases in the carotene and vitamin C intakes.

Inter- and intraexaminer reliability of nerve conduction measurements in patients with diabetic neuropathy.

We determined the inter- and intraexaminer reliability of nerve conduction measurements in six patients with diabetic peripheral neuropathy. Each patient was examined by six electromyographers on two separate occasions at least 1 week apart. We obtained attributes of nerve conduction at each examination and analyzed the data by analysis of variance. Intraexaminer reliability was high for 11 of 12 measurements, and interexaminer reliability was high for eight of twelve. Three of the four measurements that varied between examiners were either sensory or motor amplitudes, attributes frequently used to measure disease progression or to assess the result of therapeutic intervention. Our results suggest that longitudinal nerve conduction measurements used to assess worsening or improvement over time should optimally be performed by a single examiner to minimize the degree of variability associated with different examiners.

Patterns of cerebral atrophy in HIV-1-infected individuals: results of a quantitative MRI analysis.

Cerebral atrophy is a common radiologic manifestation of HIV dementia. To evaluate the relationship between cognitive impairment and cerebral atrophy, adjusting for age and immune status, we used standardized planimetry to measure the ventricle-brain ratio (VBR) and the bifrontal (BFR) and bicaudate (BCR) ratios, three measures of cerebral atrophy. We analyzed cranial MRIs of 23 HIV-1-seronegative controls (SN) and 116 HIV-1-infected individuals. Of the HIV-1-seropositive individuals, 37 had HIV dementia (DM group), 40 had neurologic or neuropsychological abnormalities insufficient for HIV dementia (NP+ group), and 39 were neurologically normal (NML group). We performed comparisons using analysis of covariance with correction for multiple comparisons. Both the VBR, a general measure of overall cerebral atrophy, and the BCR, a measure of atrophy in the region of the caudate nucleus, are significantly associated with dementia. The association is stronger for BCR enlargement than for VBR enlargement, suggesting that selective caudate region atrophy is associated with HIV dementia. These results indicate that overall cerebral atrophy and prominent caudate region atrophy are important radiographic features of HIV dementia.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed brief, comprehensive, and reliable batteries of clinical and neuropsychological tests for assessment of patients with the clinical diagnosis of Alzheimer's disease (AD). We administered these batteries in a standardized manner to more than 350 subjects with a diagnosis of AD and 275 control subjects who were enrolled in a nationwide registry by a consortium of 16 university medical centers. The tests selected for this study measured the primary cognitive manifestations of AD across a range of severity of the disorder, and discriminated between normal subjects and those with mild and moderate dementia. The batteries also detected deterioration of language, memory, praxis, and general intellectual status in subjects returning for reassessment 1 year later. Interrater and test-retest reliabilities were substantial. Long-term observations of this cohort are in progress in an effort to validate the clinical and neuropsychological assessments and to confirm the diagnosis by postmortem examinations. Although information on validation is limited thus far, the CERAD batteries appear to fill a need for a standardized, easily administered, and reliable instrument for evaluating persons with AD in multicenter research studies as well as in clinical practice.

The predictive value of a strongly positive stress test in patients with minimal symptoms.

The ability of a strongly positive stress test to predict left main coronary artery disease in people with suspected coronary artery disease but with minimal or no angina was investigated in 40 such patients. Nine had a history of myocardial infarction but no angina. Thirty-one had mild angina or a history of mild angina. The stress electrocardiograms were analyzed according to criteria known to be associated with left main coronary artery disease in moderately or severely symptomatic patients; (1) early S-T segment changes (stage I or II of exercise), (2) 2 mm or more S-T segment depression, (3) downsloping S-T segments, (4) associated exercise-induced hypotension, (5) prolonged S-T segment changes after the test (greater than or equal to 8 minutes) and (6) anterior and inferior S-T segment depression. The prevalence of left main coronary artery disease was 35 percent and that of any severe coronary artery disease 75 percent. The criterion of anterior and inferior electrocardiographic changes with exercise was most predictive of left main coronary artery disease (P less than 0.01 by chi 2). Exercise electrocardiography is useful in the prediction of left main or other severe coronary artery disease even when performed in patients who have minimal angina or in those who are asymptomatic after myocardial infarction.

Role of therapeutic plasmapheresis in the acute Guillain-Barré syndrome.

Plasmapheresis modifies the course of the acute Guillain-Barré syndrome (GBS) in terms of time-related parameters such as time on a respirator or time to achieve a specific area of improvement at specific times after onset of the illness such as at 1 month and at 6 months. Certain factors are associated with poorer outcomes in acute GBS. These include amplitude of compound muscle axon potentials on stimulating distally, time of onset of disease of 7 days or less, need for ventilatory support, and older age. Plasmapheresis, the only variable that the physician can influence, has a beneficial effect over and above all these factors.

Interstitial pneumonitis following autologous bone marrow transplantation.

Interstitial pneumonitis (IP) occurred in 20 of 143 (14%) patients who received cytoreductive therapy followed by autologous bone marrow transplantation (BMT) as treatment for malignancy. IP occurred at a median onset time of 41 days (5 to 624 days). All but three of the episodes were fatal. Of the thirteen cases in which tissue was examined, half were idiopathic; the remainder were due to various infectious agents. The actuarial incidences of idiopathic (7%) and CMV IP (2%) in these marrow autograft recipients were lower than the incidences of idiopathic (19%) and CMV IP (17%) in comparably treated recipients of allogeneic BMT (P less than or equal to 0.001 for both comparisons).

Health services use by children enrolled in a hospital-based primary care clinic: a longitudinal perspective.

The use of a hospital-based primary care clinic for health maintenance and illness care and use of the emergency room were monitored for 3 years for 293 children who had been enrolled in the clinic as infants. Infrequent users of one facet of care were infrequent users of other facets of care, and they remained so for all 3 years. The same trends were noted for frequent users. Children who used the clinic for health maintenance infrequently were more likely to have registered in the clinic after 2 months of age and to demonstrate consistently infrequent use throughout the 3 years. Children who used the clinic for illness care infrequently were more likely to have at least two siblings and to demonstrate consistently infrequent use. Children who used the emergency room infrequently were likely to have been consistently infrequent users for emergencies and illness throughout the 3 years. Conversely, those who used the clinic frequently for health maintenance were more likely to have registered before 1 month of age, to have multiple chronic conditions, and to demonstrate consistently frequent use for maintenance throughout the 3 years. Frequent users for illness care were more likely to have none or one sibling, multiple chronic conditions, and to demonstrate consistently frequent use for illnesses. Finally, children who used the emergency room frequently were likely to have multiple chronic conditions and to demonstrate sustained frequent use throughout the 3 years. These results suggest that patterns of use are established as early as the first year of life.

Childhood physical fitness tests: predictor of adult physical activity levels?

Regular physical activity has both short- and long-term health benefits in adults. No study has investigated childhood determinants of adult physical activity patterns, however. In a nonconcurrent prospective study, the physical activity levels of 453 young men, 23 to 25 years of age, were compared with their physical fitness test scores as children (10 to 11 years of age and 15 to 18 years of age). The physically active adults had significantly better childhood physical fitness test scores than did the inactive adults. In 224 children, 2 years of fitness test results were available. The risk of physical inactivity in young adulthood was linearly related to the number of low scores on the 548.6-m (600-yd) run and sit-ups tests as children (P less than .001). In stepwise multivariate discriminant analysis, the childhood 548.6-m run score was the best discriminator between currently physically active and inactive adults. Reported parental encouragement of exercise, level of education, participation in organized sports after high school, and reported spousal encouragement of exercise also contributed significantly to the discriminant function. These results demonstrate that physical fitness testing in boys facilitates the identification of those at increased risk of becoming physically inactive young adults.