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Objectives. Because psychostimulants can exacerbate preexisting motor/phonic tics in individuals with Tourette's syndrome (TS), a clinical trial was performed to examine the ability of clonidine and desipramine to modify attention-deficit hyperactivity disorder (ADHD) behaviors in children with TS + ADHD. Methods. A double-blind, placebo-controlled protocol was used in which each subject served as his or her own control and received, in a randomly assigned fashion, 6-week medication cycles with clonidine (0.05 mg four times daily), desipramine (25 mg four times daily), and placebo. Results. Thirty-seven children with TS + ADHD between the ages 7 to 13 years and of normal intellect were recruited, and 34 (31 males, 3 females) completed the entire protocol. Outcome measures for ADHD included Parent and Teacher Child Behavior Checklists (CBCL), continuous performance tests, and neuropsychologic tests of executive function. Several markers for ADHD were shown to improve significantly (P < .05) after treatment with desipramine (parent linear analogue rating, parent CBCL "hyperactivity" subscale, and teacher CBCL subscales "nervous/overactive," "anxious," and "unpopular"). Improvement with desipramine was always superior to that noted with clonidine. Clinical improvement did not correlate with drug blood levels. On measures of tic severity, neither drug made tics worse. Desipramine showed a statistically significant improvement on a global linear analogue scale, but not on the Hopkins Motor/Vocal Tic Severity Scale, the Tourette Syndrome Severity Scale, or the Yale Global Tic Severity Scale. Clonidine did not significantly alter tic severity on any measure. Conclusion. The results of this study suggest that desipramine may be a useful alternative for the treatment of symptoms of ADHD in children with TS.

Nerve conduction studies (NCS) are an integral part of the evaluation of amyotrophic lateral sclerosis (ALS) patients and are useful in distinguishing ALS from disorders that mimic it. The question often arises whether in the presence of severe atrophy and reduction of the compound muscle action potential amplitude, abnormal conduction velocity (CV), distal latency (DL), of F-wave latency (F) exceeds what can be expected from ALS alone. To determine the limits of abnormality in classic ALS, we prospectively evaluated NCS data from 61 patients who met a strict clinical definition of ALS. We ralated CV, DL, and F to distal evoked amplitude (AMP) in peroneal (n = 63 observations), median (n = 50), and ulnar (n = 52) nerves. In nerves with reduced AMP, CV rarely fell to less than 80% of the lower limit of normal, and DL and F rarely exceeded 1.25 times the upper limit of normal. Utilizing the entire data set and regression analyses, 95% confidence limits for expected values for CV, F, and DL as a function of AMP were calculated. These limits thus derived suggest criteria for NCS abnormalities in ALS and may by useful in differentiating ALS from other illnesses. © 1992 John Wiley & Sons, Inc.

A prospective, randomized, clinical trial was conducted to investigate whether a postpartum visit between a mother and her neonate's future primary care provider combined with telephone access would improve health care utilization, enhance identification of the provider as a source of advice, increase maternal knowledge of infant care, and decrease maternal anxiety and depression. Of 251 mother-neonate pairs, 122 were randomized to the control group and 129 to the intervention group. Outcome variables included health care utilization and results of maternal interviews. More mothers in the intervention group made a scheduled clinic visit in the first 30 days (P = .003), were more likely to seek some form of care at the clinic (P = .006), and tried to reach their physician by phone more often than the control group (P

We tested the hypothesis that antihistamine-decongestant combinations cause no clinically significant relief of the symptoms of upper respiratory tract infections in young children by randomly assigning 96 children to one of three treatment groups: antihistamine-decongestant, placebo, and no treatment. There were no differences among the three study groups in the proportion of children considered "better" overall by the parent 48 hours after the initial assessment (drug, 67%; placebo, 71%; no treatment, 57%; p = 0.53). There were no differences among groups in individual or composite symptom score changes. Two thirds of parents whose children were eligible for the drug trial believed that their child needed medicine for cold symptoms. In the proportion of parents believing that their child needed medicine, there was no difference between those who consented to participate and those who refused. Parents who wanted medicine at the initial visit reported more improvement at follow-up, regardless of whether the child received drug, placebo, or no treatment. We conclude that there is no clinically significant improvement in symptoms of upper respiratory tract infection, including no significant placebo effect, in young children for whom an antihistamine-decongestant is prescribed.

Objectives. Some inner-city infants grow to be successful, self-sufficient adults. This study is designed to identify characteristics from early childhood that foster or impede favorable outcomes and are useful for formulation of public policy. Methods. Population: 2694 children (G-2s), born 1960 through 1965, to 2307 inner-city women (G-1s) enrolled in the Johns Hopkins Collaborative Perinatal Study. Data: 1) prospective observations (birth through 8 years) of neurologic and cognitive development, health, behavior, and family and neighborhood socioeconomic characteristics and 2) completed interviews with 1758 G-2s (age 27 to 33) and 1552 G-1s, bridging the period from age 9 to present status. An intergenerational, life course model of development identified significant characteristics and events associated with G-2 outcome (education, physical and mental health, healthy lifestyle, and financial independence of public support, emphasizing educational attainment of a high school diploma or a graduate equivalency degree). Multiple logistic regression equations identified independent, predictive variables during infancy, preschool and early school years, and adolescence. The probability of a good outcome was estimated in the presence of combinations of the six variables most strongly associated with that outcome. Results. Among G-2s, 79% had a successful outcome for education, 60% health, 70% lifestyle, and 76% for financial independence. Black G-2s had more favorable outcomes than white G-2s in education and lifestyle, whites for financial outcome; health did not differ by race. The six variables most predictive of adult education were: G-1 education at G-2 birth and G-2 attainment of honor roll, average or better reading skills at 8 years, avoidance of regular smoking, and pregnancy before age 18, and not repeating a grade in school. Conclusions. Substantial proportions of inner-city children become successful adults. Attention to improving public education, particularly language and reading skills, and the prevention of smoking and adolescent pregnancy are clearly indicated.

Children with inborn errors of urea synthesis who survive neonatal hyperammonemic coma commonly exhibit cognitive deficits and neurologic abnormalities. Yet, there is evidence that ammonia is not the only neurotoxin. Hyperammonemia appears to induce a number of neurochemical alterations. In rodent models of hyperammonemia, uptake of L-tryptophan into brain is increased. It has been reported that in an experimental rat model of hepatic encephalopathy, in the ammonium acetate-injected rat, and in patients with hepatic failure and inborn errors of ammonia metabolism, quinolinate, a tryptophan metabolite, is increased. Elevations in quinolinate are of particular concern, as quinolinate could excessively activate the N-methyl-D-aspartate subclass of excitatory amino acid receptors, thereby causing selective neuronal necrosis. We sought to identify an animal model that would replicate the increases in quinolinate that have been associated with hyperammonemia in humans. Levels of quinolinate were measured in hyperammonemic urease-infused rats and ammonium acetate-injected rats. In the urease-infused rat, brain tryptophan was doubled, and serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly increased. Yet, despite the increase in tryptophan and evidence for increased metabolism of tryptophan to serotonin, there were no observed increases of quinolinate in brain, cerebrospinal fluid, or plasma. In the ammonium acetate-injected rat, significant increases of 5-hydroxyindoleacetic acid in cerebral cortex were also observed, but quinolinate did not change in cerebrospinal fluid or cerebral cortex. In summary, we were unable to demonstrate an increase of quinolinate in brain or cerebrospinal fluid in these rat models of hyperammonemia.

Nerve conduction studies are widely employed in evaluating patients with peripheral nerve disease and are often used serially to measure disease progression or to assess a therapeutic intervention. We determined the inter- and intra-examiner reliability of electrophysiological data by performing serial nerve conduction studies on 7 normal subjects. A high degree of inter-examiner reliability was present, but significant inter-examiner differences were found. Our results suggest that if nerve conduction studies are to be used longitudinally, they should optimally be performed by a single examiner to minimize the degree of variability associated with different examiners.

We conducted a case-control study to examine the correlates of emergency room use in the first year of life, particularly the role of parental health beliefs, among the families of inner-city children enrolled in a hospital-based primary care program. Data were collected by structured interviews and by medical record review. Emergency room users were more likely to have single mothers and to have acute, recurrent medical conditions than were non-users. Health beliefs differed between groups by maternal report of worry about the kinds of illnesses that her child acquires. Emergency room use was predicted by: maternal marital status, maternal worry and concern that illness interferes with her child's activity, acute recurrent illnesses, hospitalization. This model may be applicable to other populations in designing intervention strategies to modify emergency room utilization.

In this chapter we call upon our experiences as principal statistician (E.D.M.) and principal investigator (G.M.M.) in a controlled study of plasmapheresis in the treatment of the acute Guillain-Barre Syndrome (GBS) [1–3]. We will present a description of the disease and a brief history of attempts at therapy of this disorder. The conceptual development and design used in our study are emphasized. Comprehensive results are given and compared with similar studies carried out by Swedish [4] and French [5] investigators. In addition, the statistical methodology that was used and the rationale for its choice are presented. In our discussion, we identify several points learned from our experiences. In particular, we stress the importance of standardization of clinical data, definition of the endpoints involved, the strategy for choosing the sample size, and the choice of statistical methods, as dictated by the analytic definition of the problem.

To the Editor: The article by Chaudhry et al [1] addresses the reliability of nerve conduction studies (NCS) in patients with diabetic neuropathy. Perhaps the authors would consider providing additional information regarding the coefficient of variation, the standard deviation/mean, of their findings. Unlike ANOVA, the coefficient of variation can be readily understood by nonstatisticians and easily performed. It describes reliability in absolute numbers suitable …

Between 1966 and 1976, heights and weights were determined yearly on all available children from 163 families who had had at least one child successfully treated for malnutrition between 1961 and 1971 and from eight families who had adopted such a child. Between 1959 and 1976, a total of 72 fathers departed from these families: 12 died, 47 deserted, six were jailed, and seven left to look for work elsewhere. Heights and weights as Z scores and the weight age/height age ratios were analyzed, when available, during four periods around the date of the event: 6 to 18 months before (period 1B), 0 to 6 months before (period 2B), 0 to 6 months after (period 3A), and 6 to 18 months after (period 4A). Mean Z scores for all children measured in the period were already low (-0.26 ± 0.93 and -0.25 ± 0.95) during period 1B, were higher during period 2B, (-0.15 and 0.04), lower during period 3A (-0.39 and -0.46), and similar to original levels during period 4A (-0.37 and -0.27). Mean weight age/height age was low (0.93 ± 0.17) only during period 3A for children 2 to 18 years of age. In paired comparisons for children measured during any two periods there were significant increases in Z height and Z weight from periods lB to 2B and from periods lB to 4A in children < 2 years of age and a significant decrease in the weight age/height age ratio from periods lB to 3A in those 2 to 18 years of age. Loss of father had little or no further impact on the already poor growth of these children.

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.

Summary Selected questions from the Wechsler Intelligence Scale for Children (WISC) were readministered to 200 inner-city seven-year-olds after completion of the standard protocol. The readministration was specifically structured to ascertain the reasoning by which children arrived at their answers. A system was developed for the classification of errors. Four categories of error, in addition to basic lack of knowledge, were demonstrated. The categorization of errors, by type, permitted examination of the reasoning underlying responses. It was apparent that some reasonable alternative answers existed which received no credit or only partial credit when the standard WISC protocol was applied. These results may suggest modifications to compensate for some of the limitations imposed by standardized test procedures.

Selected tests of lymphoid function were used to screen a population of volunteer hemapheresis donors. Testing included: 1) absolute lymphocyte numbers, and percentage of T-cell, B-cell, and mononuclear phagocytes, 2) serum immunoglobulins, and, 3) in vitro proliferative responses to lectin mitogens (phytohemagglutinin, concanavalin A, and pokeweed mitogen), soluble antigens (staphylococcal filtrate, candida, and streptococcal varidase), and cell-bound alloantigens (mixed lymphocyte culture). A control population of first-time plateletpheresis donors was examined similarly. Regular donors manifested a small but statistically significant decrease in absolute lymphocyte counts (p less than 0.02), and IgM (p less than 0.02) compared to controls. Leukapheresis donors also manifested significant decreases in percentage of T cells (p less than 0.02). These findings are qualitatively similar to changes reported following intensive lymphocytapheresis and indicate the need for conservative policies regarding donation frequency in hemapheresis programs.

To determine whether acetaminophen affects the duration or severity of childhood varicella.Randomized, double-blind, placebo-controlled trial.Office- and hospital-based pediatric practices.Seventy-two children between 1 and 12 years of age entered the study. One child was withdrawn because of high fever, and three children did not complete the study; 31 received placebo and 37 received acetaminophen.Acetaminophen, 10 mg/kg/dose, was given at 8 AM, 12 PM, 4 PM, and 8 PM for 4 days. Placebo was given to the control group. Itching, appetite, activity, and overall condition were measured for 6 days. The time to last vesicle formation, time to total scabbing, and time to total healing were measured until complete resolution of the exanthem.The following results were better in the placebo group (p less than .05): time to total scabbing 5.6 days (SD 2.5) versus 6.7 days (SD 2.3) in the acetaminophen group, and itching on day 4 in the placebo group (symptom score 2.9 (SD 0.20) vs 2.2 (SD 0.26]. Activity was better in the acetaminophen group on day 2 (3.13 (SD 0.23) vs 2.82 (SD 0.24].These results provide evidence that acetaminophen does not alleviate symptoms in children with varicella and may prolong illness.

Recent studies suggest that infant behavior and psychological test performance are impaired by iron deficiency and may be improved by iron. Comparable studies have not been performed in older populations. Young women early in pregnancy whose nutritional intake may be impaired by poverty constitute a high-risk population. Women aged 14-24 years coming for prenatal care at or before 16 weeks gestation whose hematocrits were greater than or equal to 31% were randomized in a double-blind trial to receive vitamins supplemented with iron (experimental group) or vitamins alone (controls). Hematologic status and tests of short-term memory and attention span were assessed at entry and conclusion of the one-month treatment period. The experimental group showed significant improvement on the most sensitive measure of short-term memory and three subtests. On comparison of the change between initial and final scores, the experimental group showed significant or borderline greater improvement than controls on three tests. These results indicated a beneficial effect of iron therapy on psychometric test-score performance.

A review of 277 newborns with neonatal seizures enrolled in the Collaborative Perinatal Project revealed a mortality of 34.8%. Of the 181 survivors, most followed up to age 7 years, 70% were normal. Thus, despite the fact that seizures are a major indicator of perinatal asphyxia and a predictor of subsequent neurologic deficit, most infants with neonatal seizures who survived did well. Thirteen percent had cerebral palsy, 19% had an IQ

Unstable angina that occurs in the early postinfarction period is associated with an increased incidence of unfavorable cardiac events despite aggressive medical therapy. We examined the results of coronary angioplasty in 47 consecutive patients with postinfarction unstable angina who were referred for the procedure 12.9 +/- 7 days following myocardial infarction, 14 of which were Q wave and 33 of which were non-Q-wave. Coronary angioplasty was performed on a total of 55 arteries with a mean predilatation stenosis of 95 +/- 8%. These included 46 infarct-related arteries and nine noninfarct arteries. Double-vessel angioplasty was performed in eight patients. Successful coronary angioplasty (greater than 30% reduction of predilatation stenosis) was achieved in 43 patients (91%), with a mean residual stenosis of 33 +/- 28%. There was one in-hospital death, one patient required emergency bypass surgery, and two patients had early reocclusion resulting in myocardial infarctions. The 39 patients who had successful angioplasty procedures and who were discharged from the hospital without an unfavorable outcome were followed for 16.3 +/- 7 months, and repeat coronary angioplasty was required in five patients from 45 to 105 days after the initial procedure. Two patients had subsequent elective bypass surgery, one had a recurrent myocardial infarction, and one patient had a noncardiac death. For selected patients with suitable coronary anatomy, coronary angioplasty appears to offer an efficacious therapeutic option for early postinfarction unstable angina.

A multivariate analysis of perinatal events occurring in infants with neonatal seizures who were enrolled in the National Collaborative Perinatal Project allowed prediction of outcome. This prediction of death or of mental retardation, cerebral palsy, or epilepsy was empirically confirmed 64% to 83% of the time. In an infant with neonatal seizures, a five-minute Apgar score of less than 7, the need for resuscitation after 5 minutes of age, the onset time of the seizures, and a seizure lasting more than 30 minutes are the best early predictors of which infants will die or will have significant neurologic sequelae. It is hypothesized that neonatal seizures may be a better indicator of the severity or duration of intrauterine asphyxia than the Apgar score. In the neonate with seizures, the use of the formula may allow identification of infants at high risk for adverse outcomes.

This study demonstrates the feasibility of a randomized controlled investigation of terminating the phenylalanine-restricted diet in four-year-old children with phenylketonuria. The parents of 14 of 16 children gave informed consent, knowing their children would be randomly assigned to either a diet-continuation or a diet-termination group. Compared with the continuation group, the mean serum phenylalanine of the termination group was 15.1 mg per dl higher (P less than 0.005) one year, and 9.2 mg per dl higher (P less than 0.025) two years after diet termination. Mean weight gain between four and six years of age was 3.4 kg greater in the terminated than in the continued group (P less than 0.01). There were no significant differences in mean head circumferences, height or performances on psychologic tests. At age six, mean I.Q. in the terminated group was 99.8, in those continuing the diet 103.6. Children in both groups showed some subtest scatter in memory and concentration. Thus, no harmful effects of diet termination were noted, but a longer period of observation in a larger number of subjects is needed.

Rats implanted with subcutaneous or intraperitoneal osmotic minipumps infusing 0.8-1.25 IU urease/kg/h develop sustained hyperammonemia (range 137-497 microM, controls 88 +/- 51 microM +/- SD) for 5-7 days. Glutamine levels are also significantly elevated in plasma (677 +/- 166 versus 428 +/- 122 microM) and cerebral cortex (13.2 +/- 9.8 versus 4.7 +/- 2.8 nmol/mg tissue). Neurobehavioral abnormalities include decreased food intake and increased stereotypic activity. Increased serotonin turnover was suggested by elevated levels of tryptophan and 5-hydroxyindoleacetic acid in cerebral cortex, brain stem, and cerebellum of urease-infused compared to sham-operated animals. There were no changes in norepinephrine or gamma aminobutyric acid, and there was no correlation between the degree of hyperammonemia or glutaminemia and brain levels of tryptophan or biogenic amines. Animals receiving a tryptophan-deficient diet had significantly lower levels of tryptophan and 5-hydroxyindoleacetic acid in brain regions compared to animals receiving a normal tryptophan intake, under both control and hyperammonemic conditions. Despite the prevention of increased serotonin flux in hyperammonemic animals receiving a tryptophan-deficient diet, food intake and weight declined and there was increased stereotypic behavior.

Since metabolic activation is known to mediate mutagenic and carcinogenic actions of certain chemicals, it is possible that embryopathic effects might also result from formation of reactive metabolites in fetal tissue. We evaluated this possibility by examining the activation of BaP 3 by fetal mouse liver homogenates ( + NADPH) to a mutagen(s) active in the “Salmonella-microsome” assay. Three inbred mouse strains known to have high (B6), intermediate (C3H) and low (D2) inducibility of AHH and one random bred strain (CD1) were tested on gestational day 17, four days after an enzymeinducing dose of polychlorinated biphenyls. BaP induced TA1538 revertants in the presence of fetal liver homogenates from all strains with the order of activity being CD1 > B6 > C3H > D2. Although the number of revertants per mg fetal liver protein was only 5–10% of that found with maternal liver, it was linearly related to induced AHH activity measured by the fluorescence procedure. In contrast, the mutagenizing activity of placenta and whole fetus (minus liver) was lower than fetal liver and did not correlate with induced AHH activity. Activating potency did not correlate with either EH activity or the ratio of AHH/EH in maternal liver, fetal liver or placenta. These results support the postulated mechanism for embryopathic effects of chemicals that undergo metabolic activation to reactive metabolites and provide an explanation for genetically determined variation in response.

In the study of human populations, much emphasis is placed on the concentration of lead in whole peripheral blood. There is a considerable body of evidence which indicates that this measurement reflects recent and current assimilation of lead. While broad ranges in blood lead concentration have been associated with differing risks of toxicity for groups, it is not a precise index of adverse effect per se, even at elevated levels. Within the red blood cell itself there is not a close association between the concentration of lead and such adverse metabolic effects as the increased loss of potassium caused by lead. Above the apparent “threshold zone” of approximately 30–50 μg Pb/100 ml whole blood, equivalent metabolic effects on heme synthesis may be seen over an interval of at least 20 μg Pb/100 ml whole blood. This variation will be examined with particular reference to the interrelationship between the concentrations of lead and protoporphyrin in peripheral blood. The data indicate that limitations in both precision and accuracy of measurement account for a relatively small fraction of the observed variations. Together with other experimental and clinical information, they suggest that concurrent dietary deficiency of iron may be one of the important modifying factors in the responses of subjects with increased lead absorption. It is suggested that suspected adverse effects upon the various organ systems associated with increased lead absorption be measured directly and that the CaEDTA mobilization test for lead should be more fully explored as a measure of the “metabolically active” fraction of the total body lead burden.

In many infants with phenylketonuria (PKU) the concentration of blood phenylalanine rises only minimally during the first three days of life and infants of both sexes may be missed by screening. During this period the rate of rise of blood phenylalanine is slower in females than in males and, on the fourth day of life, significantly more males than females are discovered by screening. The ratio of males to females who are screened on the fourth day is not higher than on the previous days. The large proportion of all infants who were screened on the fourth day of life probably accounts for the previously described excess of males; females are being missed. In 12 states providing data 44.4% of all infants were screened on one of the first three days of life and 25% on the fourth day.

The performance on a neurological test battery of 33 language-impaired children who had no gross neurological findings and 37 normal children controlled for age, performance IQ, and socioeconomic status was compared. The language-impaired group was distinguished by less efficient performance in a number of areas, particularly in tasks involving involving rate of movement, perception of dichhaptic stimuli, and left-right identification. Discriminant function analysis identified six variables that correctly classified 87% of the population into their respective normal and language-impaired groups.

The digestibility and protein quality of the white potato were studied in 11 infants, ages 8-35 months, recovering from malnutrition. Seven 9-day dietary periods comprised the study. Digestibility was assessed by metabolic balance during the last 6 days of dietary periods in which potato provided 25%, 50% or 75% of dietary energy. Casein-based control dietary periods preceded and/or followed each potato dietary period. Fecal wet and dry weights, fecal energy, computed fecal carbohydrate and fecal fat during consumption of the 25% potato diet did not differ from control. Analysis of variance showed that consumption of increasing amounts of potatoes produced a significant linear increase in all parameters of digestibility except fecal fat. Fecal wet weight and energy content during the 75% potato period were more than double control values. Regression analysis of data from potato dietary periods showed fecal wet weight to be an excellent predictor of fecal dry weight (r = 0.904), energy content (r = 0.785) and computed fecal carbohydrate (r = 0.770). Protein quality of potato was assessed with N balance studies during the dietary periods in which potato provided all dietary protein (approximately 5% protein kcal). Apparent N retention was 78% of that from an isonitrogenous casein control diet. Decreased apparent N absorption was primarily responsible for the difference; the "biologic value" (percent of absorbed N that was retained) was similar for both diets.

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.

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.

We assessed the efficacy of adding nifedipine to the conventional treatment of unstable angina in 138 patients in a prospective, double-blind, randomized, placebo-controlled trial. There was no difference between the two groups in the dose of conventional antianginal medication or in age, prior myocardial infarction, ejection fraction, or other risk factors. Failure of medical treatment (defined as sudden death, myocardial infarction, or bypass surgery within four months) occurred in 43 of 70 patients given placebo and in 30 of 68 given nifedipine. Kaplan-Meier survival-curve analysis of the number and time dependence of treatment failures demonstrated a benefit of nifedipine over placebo (P = 0.03). The benefit was particularly marked in patients with ST-segment elevation during angina (P = 0.02). Side effects (transient hypotension or diarrhea) required withdrawal of the drug from four patients given nifedipine and from one given placebo. We conclude that the addition of nifedipine to conventional therapy is safe and effective in unstable angina.

Serum IgG, IgM, and IgA were measured in 316 infants younger than 12 months of age. Information including the child's race, sex, age, and past history of infections or atopy was collected. Birth records were also reviewed to ascertain the child's birthweight and gesta tional age. Serum IgG levels were higher in black infants than in white infants after the age of 4 months. Serum IgM levels were higher in black females than in black males for infants older than 1 month. For infants younger than 4 months of age, those weighing less than 2500 g at birth had lower IgG levels than those weighing more than 2500 g. Infants younger than 1 month whose gestational age had been less than 36 weeks had lower IgG levels than those greater than 36 weeks. Infants aged 1 to 4 months whose gestational age had been less than 36 weeks had lower IgG levels than did those 40 or more weeks. Infants with a positive history for atopy had lower IgG levels than similarly aged infants with a negative history.

A simple screening technique for measuring protoporphyrin (PROTO) in acidified acetone extracts of capillary blood is described. A statistically significant linear relationship was found between blood lead concentration and log e PROTO concentration. The relationship is sensitive to mild degrees of anemia. The hematocrit may be used to compensate for concurrent anemia when screening for increased lead absorption. When this PROTO assay-microhematocrit procedure was was used prospectively as a screening technique for increased lead absorption, 95 per cent of children with ⪖50 μg Pb were identified, while 90 per cent of those with

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 came 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.

The relationships between initial and follow-up blood phenylalanine concentration and between initial concentration and age were examined in infants with elevated screening tests. Data were provided by health departments and phenylketonuria (PKU) clinics. Among infants who attained levels of 20 mg/100 ml or more the following was observed: (1) one-fourth had only minimal elevations (to less than 10 mg/100 ml) on the initial screening test; (2) of those with minimal elevations 66% were screened on or before the third day of life; (3) most of those whose initial elevations were more than minimally elevated and most of those with minimal elevations who were screened early had follow-up phenylalanines of 30 mg/100 ml or more. In contrast, those with minimal initial elevations who were screened late were more likely to have follow-up phenylalanines between 20 and 30 mg/100 ml. They may represent a different form of PKU. The findings suggest that as long as most infants in the United States continue to be screened on or before 4 days of age, some infants with PKU will be missed.

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. Patients with continued symptoms of rest angina, however, may experience adverse ischemic events with nifedipine withdrawal.

A c c ~J R A T ~ diagnoses and proved regimens are of limited use unless patients understand and comply with instructions. This consideration is especially important in low-income areas, where medical services are not only scarce but often inappropriate? This study was designed to establish whether nurses working with indigent families in an outpatient setting could improve knowledge of and compliance with a difficult regimen for a nonacute condition.

Cord serum immunoglobulin G and M levels and their relationship to race, sex, birth weight, and clinical status are examined. The levels of both immunoglobulins are not related to sex. Negro infants have higher IgG and lower IgM levels than Caucasians. IgG levels and birth weight are associated, smaller infants having lower levels. The previously reported relationship between high levels of IgM and congenital infection is confirmed. In addition, a significant relationship between very low levels and adverse fetal outcome is demonstrated by neurologic abnormalities, severe congenital malformations, and perinatal deaths.

Of 1,394 prenatal patients, 356 registered early and were euthyroid continuously with uncomplicated pregnancies and deliveries of single neonates weighing at least 2,500 grams; 131 others were hypothyroxinemic during uncomplicated pregnancies. For euthyroid mothers, 227 progeny, age 4, and 57, age 7 years, had standard psychological examinations of the Collaborative Study of the National Institute of Neurological Diseases and Stroke. At 4 years, 55 children born to girls age 15 to 17 and 33 children born to women over 35 had significantly lower mean Intelligence Quotients than 18 children born to mothers age 23 and 24. At 7 years, 19 children born to girls age 15 to 17 and 9 children born to women over 35 had significantly lower scores than 10 progeny of women age 25 to 34. Compared to progeny of euthyroid women, lower scores of 4-year-old children of hypothyroxinemic, untreated mothers have been described. At 7 years, 4 of 11 (36 per cent) progeny of hypothyroxinemic, untreated women scored in the dull normal range or below, compared to only 9 of 57 (16 per cent) of children of euthyroid mothers.

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.

We conducted a randomized, double-blind, crossover study comparing the antiemetic efficacy of dexamethasone and prochlorperazine in 42 patients with cancer who were receiving outpatient chemotherapy, mainly without cisplatin. Patients experienced significantly less nausea and vomiting with dexamethasone than with prochlorperazine (P less than 0.02 and less than 0.03, respectively). Twenty-five patients experienced no nausea with dexamethasone, as compared with 14 patients taking prochlorperazine (P less than 0.001). Similarly, 29 patients receiving dexamethasone did not vomit, as compared with 18 receiving prochlorperazine (P less than 0.001). Somnolence was the most frequent side effect, occurring in 60 per cent of patients receiving prochlorperazine and in 12 per cent of those receiving dexamethasone (P less than 0.001). Patients also experienced less suppression of appetite while receiving dexamethasone (P less than 0.02). We conclude that dexamethasone is an effective and safe antiemetic in patients receiving cancer chemotherapy without cisplatin.

A double-blind controlled trail of anti-Pseudomonas chemotherapy was carried out in 24 exacerbations of pulmonary disease in patients with cystic fibrosis. Fifteen exacerbations were treated with oxacillin plus sisomicin and carbenicillin (treatment group); nine were treated with oxacillin alone (control group). The planned length of treatment was 14 days. The difference between the failure rate in the treatment group (3/15) and the control group (7/9) was statistically significant (P less than 0.015). The difference in improvement of forced expiratory volume in 1 second was also significant (P less than 0.025). At the end of the study, Pseudomonas aeruginosa was still present in the sputum of all nine patients in the control group, but was not isolated from six of the 15 patients in the treatment group. The data suggest a beneficial role for anti-Pseudomonas chemotherapy in the treatment of acute pulmonary exacerbations in patients with cystic fibrosis.

• The group B β-hemolytic streptococcus is responsible for an escalating frequency of neonatal meningitis. Of the 18 consecutive cases we report in this study, the mortality was 17%. Among the 15 survivors, there were two children with extensive neurological and psychological impairment. There were no major differences between the survivors and controls in tests of hearing and language function, social skills, and psychological testing. There was a greater number of minor neurological signs among the study group. The mortality and morbidity of group B β-hemolytic streptococcal meningitis is apparently substantially less than that of all other types of neonatal bacterial meningitis. (Am J Dis Child131:845-849, 1977)