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Background: Cognitive deficits have been reported in patients after coronary artery bypass grafting, but the incidence of these deficits varies widely. We studied prospectively the incidence of cognitive change and whether the changes persisted over time., Methods: Cognitive testing was done preoperatively and 1 month and 1 year postoperatively in 127 patients undergoing coronary artery bypass grafting. Tests were grouped into eight cognitive domains. A change of 0.5 standard deviation or more at 1 month and 1 year from patient's preoperative Z score was the outcome measure., Results: We identified four main outcomes for each cognitive domain: no decline; decline and improvement; persistent decline; and late decline. Only 12% of patients showed no decline across all domains tested; 82% to 90% of patients had no decline in visual memory, psychomotor speed, motor speed, and executive function; 21% and 26% had decline and improvement in verbal memory and language; approximately 10% had persistent decline in the domains of verbal memory, visual memory, attention, and visuoconstruction; and 24% had late decline (between 1 month and 1 year) in visuoconstruction., Conclusions: This study establishes that the incidence of cognitive decline varies according to the cognitive domain studied and that some patients have persistent and late cognitive changes in specific domains after coronary artery bypass grafting.

Background: Stroke occurs after coronary artery bypass grafting with an incidence ranging between 0.8% and 5.2%. To identify factors associated with stroke, we prospectively examined a study cohort and tested findings in an independent validation sample., Methods: The study cohort comprised 456 patients undergoing coronary artery bypass grafting only, and the validation sample comprised 1,298 patients. Stroke was detected postoperatively by the study team and confirmed by neurologic consultation and computed tomographic scanning., Results: Five factors taken together were correlated with stroke: previous stroke, presence of carotid bruit, history of hypertension, increasing age, and history of diabetes mellitus. The only significant intraoperative factor was cardiopulmonary bypass time. Probabilities were calculated, and patients were placed into low, medium, and high stroke-risk groups. In the validation sample, this model was able to rank the majority of patients with stroke into the high-risk group., Conclusions: These five factors taken together can identify the risk of stroke in patients having coronary artery bypass grafting. Recognition of the high-risk group will aid studies on the mechanism and prevention of stroke by modification of surgical procedures or pharmacologic intervention.

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., 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.

The implantable cardioverter defibrillator (ICD) is an expensive, widely used device for severe ventricular arrhythmias. Marginal cost-effectiveness analysis is a technique to examine the incremental cost of treatment strategy in relation to its effectiveness. In this study, we used this technique to analyze the cost-effectiveness of the ICD compared with that of electrophysiology (EP)-guided drug therapy and examined ways in which it may be improved. We analyzed Michigan Medicare discharge abstracts (1989 to 1992) and local physician visit, test, and ICD charges. Effectiveness was from 218 previously described patients with ICDs in whom the time of first event (first appropriate shock or death) was determined and presumed to represent "control" (EP-guided drug therapy) mortality. We assumed a 4-year life cycle for the ICD generator and 3.4% operative mortality and used a 5% discount to prevent value. Data were analyzed in a 1-month cycle Markov decision model over a 6-year horizon, and results were updated to 1993 dollars. ICD effectiveness was an increase in discounted mean life expectancy of 1.72 years. Cost-effectiveness was $31,100/year of life saved (YLS). Results were minimally or modestly sensitive to variations in preoperative mortality; resource use; consideration only of patients with ICDs who were receiving any antiarrhythmic drug or specifically amiodarone; and to a decrease in the percentage of first shocks that would equal death without the ICD until the assumed percentage decreased to < 38%. At ejection fraction of < 0.25 and > or = 0.25, cost-effectiveness was $44,000/YLS and $27,200/YLS, respectively, and without preimplant EP study was $18,100/ YLS.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Although the cause of amyotrophic lateral sclerosis (ALS) remains unknown, recent studies have suggested an autoimmune mechanism of pathogenesis. Previous trials of immunosuppressive treatment have yielded inconclusive results. Our study was designed to determine whether more powerful and prolonged immunosuppression, produced by total lymphoid irradiation (TLI), would alter the course of ALS. In a double-blind, randomized, placebo-controlled study, 30 patients with classic ALS were treated with TLI, and 31 were given sham radiation. Quantitative measurements of muscle strength, functional motor activity, and humoral and cellular immune status were followed for 2 years, or until death or respirator dependence. Motor function in the TLI-treated and control groups showed no significant differences throughout the study. Overall survival was not significantly different in the TLI-treated and control groups. TLI effectively suppressed cellular and humoral immune function throughout the 2-year study period. Analysis of the relationship between immunosuppression and motor functions showed no consistent effect of treatment. We conclude that powerful and prolonged immunosuppression produced by TLI did not benefit patients with ALS. This fails to support the concept of an autoimmune mechanism of pathogenesis of ALS.

Factors related to the amount of health care used by 5- to 11-year-old children in a health maintenance organization (HMO) were investigated using a comprehensive multivariate model that assessed the contribution of child health need, mental health, and social functioning; maternal mental health, social support and health care utilization; and family functioning and life events. Mothers reported on the 450 participating children. Health care visits for a two-year retrospective period were obtained from the computerized encounter system. Child health need and maternal patterns of health care use were powerful predictors of the overall amount of health care used, and these factors discriminated high users from low users of care. Family conflict was associated with a higher volume of care, while children's depressive symptoms and non-white race were related to lower use. Maternal social support, mental health, and life events were not predictive of use in either full multivariate model. Enabling factors were held relatively constant by participation of all families in a prepaid HMO. The multiple regression model explained 33% of the variance in use, slightly more than in previous studies of children's health care use. When included in a comprehensive analysis, child and family psychosocial characteristics help to explain children's health care use beyond what is possible using simple health and illness variables. The implications of these findings in the development of further research and to the practice of routine pediatric care are discussed.

Between 1984 and 1991 24 patients with severe aplastic anemia (SAA) were transplanted with HLA identical sibling donor BM. The overall long-term survival was 79 +/- 8%. The average age was 21 years (range 4-53 years) and the median pre-transplant disease duration was 35 days (range 12-2998 days). Over one-half (15 of 24) of the patients had received > 10 units of blood product transfusions prior to BMT. The pre-transplant conditioning regimen consisted of 200 mg/kg cyclophosphamide (CY). Cyclosporine (CYA) was administered from 2 days prior to BMT and continued for 6-12 months. Two of the 24 patients failed to achieve primary engraftment (FTE). One of these patients had autologous recovery of BM function and is alive and well. Five of the 22 patients who engrafted failed to sustain engraftment (FTSE). Of these, three are alive and well following a second BMT or marrow boost. Only 1 of the 22 patients who engrafted had clinically significant (i.e. Stage II-IV) acute GVHD. No patient developed chronic GVHD. Our results indicate that BMT following a regimen consisting of CY with the continuous use of CYA in the post-transplant period is well tolerated and associated with excellent long-term survival. The high incidence of secondary graft instability (i.e. FTSE), however, suggests that future studies should focus on post-transplantation immunomodulation.

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.

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), or 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 related 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 be useful in differentiating ALS from other illnesses.

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.

Myocardial reoxygenation injury may be attenuated by oxygen free radical scavengers, arguing for a role of oxygen radicals in this process. To determine whether free radical scavengers affect reoxygenation injury in isolated cardiac myocytes, resting rat ventricular myocytes were exposed to hypoxic (PO2 less than 0.02 mm Hg) glucose-free buffer alone (n = 50) or with the addition of the oxygen radical scavengers 1,3-dimethyl-2-thiourea (DMTU, 25 mM, n = 46), human recombinant superoxide dismutase (SOD, 1,000 units/ml, n = 40), or the combination of these agents (n = 41). All cells responded by undergoing contracture to a rigor form. Hypoxia was then continued for a second period (T2), the duration of which correlates inversely with survival. After reoxygenation, cells either retained their rectangular shape (survival) or hypercontracted to a rounded form (death). For the group of cells with a T2 period greater than 30 minutes, no cell exposed to buffer alone (n = 20) or to SOD (n = 16) survived, in contrast to 15 of 24 (63%) cells exposed to DMTU. The addition of SOD to DMTU offered no advantage to DMTU alone. The protective effect of DMTU was not observed when it was added at reoxygenation, suggesting that this agent has an important effect during the hypoxic period when intracellular Ca2+ is known to rise, most likely because of the reversal of Na(+)-Ca2+ exchange. Therefore, the effects of DMTU on Ca2+ regulation (indexed by indo-1 fluorescence) during hypoxia were studied. DMTU significantly blunted the [Ca2+] rise during the hypoxic period.(ABSTRACT TRUNCATED AT 250 WORDS)

The protective effect of nicardipine (1 and 4 microM) against reoxygenation injury was studied in an unstimulated rat single myocyte oxygen paradox model in comparison with control (no drug) or nifedipine (1 microM). Either concentration of nicardipine was strongly protective, approximately doubling the duration of ATP depletion (rigor) that cells could withstand without undergoing hypercontracture when reoxygenated. Nifedipine (1 microM), which matched the negative inotropic effect of nicardipine (4 microM) (as measured by extent of shortening when stimulated), had no protective effect against reoxygenation injury. Neither drug affected the time to rigor, which is a measure of the rate at which the resting cell consumes its endogenous glycogen stores during anaerobic metabolism. Intracellular calcium, measured with the fluorescent probe indo-1, which partitions into both cytosol and mitochondria, rose progressively throughout the rigor period. This rise in calcium was almost totally suppressed by nicardipine (1 microM) but was unaffected by nifedipine. We conclude that nicardipine possesses a direct protective effect on the myocardium not shared by all dihydropyridines. This effect is associated with the prevention of intracellular, and probably mitochondrial, calcium loading but is probably not due to blockade of the L-type calcium channel or reduction of metabolic rate.

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 intra-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.

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 less than .001). There were no differences between the groups' emergency room utilization, the percent who received immunizations by 90 days of age, maternal knowledge of infant care, maternal anxiety, or postpartum depression. The intervention succeeded in improving some measures of health care utilization and results suggest that the relationship between the mother and clinician was strengthened.

Background: Two hundred eighteen patients were evaluated in a two-phase approach (time to first appropriate discharge, survival after discharge) to identify factors that may be related to maximal benefit derived from use of an automatic implantable cardioverter-defibrillator (AICD)., Methods and Results: One hundred ninety-seven patients survived implantation of AICD, with or without concomitant cardiac surgery. One hundred five patients had an AICD discharge associated with syncope, presyncope, documented sustained ventricular tachycardia or fibrillation, or sleep at 9.1 +/- 11.1 months after implantation. Patients survived 23.8 +/- 18.0 months after AICD discharge. Left ventricular dysfunction (p = 0.008 for ejection fraction less than 25%) was associated with earlier AICD discharge and shortened survival after AICD discharge (p = 0.008 for ejection fraction less than 25%; p = 0.01 for New York Heart Association functional class III and IV). beta-Blocker administration (p = 0.006) and coronary bypass surgery (p = 0.06) were associated with later AICD discharge. Coronary bypass surgery (p = 0.035) but not beta-blockers was associated with more prolonged survival after AICD discharge., Conclusions: These data suggest that a relatively easy algorithm can be applied to predict which patient will benefit most from AICD implantation.

To evaluate the effect of long-term bronchodilator therapy in CF patients with demonstrated bronchial hyperresponsiveness, we first performed methacholine challenges to determine responsiveness, then entered 27 patients (16 methacholine responders and 11 nonresponders) into a two-month double-blind crossover trial of albuterol, 90 micrograms by inhalation four times a day vs placebo. Among the responders, daily PEFR measures improved significantly more during treatment with albuterol (12 +/- 32 L/min) than with placebo (-0.4 +/- 19 L/min; p less than 0.05). In addition, a clinically important level of improvement in PEFR (15 percent increase) was reached significantly more frequently in the responders. Methacholine nonresponders had no change in PEFR on either albuterol or placebo. Daily symptom scores as well as spirometry measurements at biweekly visits did not show significant changes. We conclude that long-term therapy with inhaled albuterol improves lung function in CF patients, but only in those with bronchial hyperresponsiveness as demonstrated by methacholine challenge.

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.

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 was 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.

To explore some determinants of physicians' decisions to change practice habits, we posed three questions: To what extent are some particular innovations diffused among office-based primary care physicians? What characterizes the physicians who have adopted these innovations? And, what caused them to change their behavior and adopt the innovations? Three "markers," recent innovation in medical practice, were chosen using an expert consensus technique. A telephone survey of 200 office-based pediatricians was conducted, and the physicians were asked whether or not they used the following three innovations in medical practice: continuous rather than intermittent phenobarbital for the prevention of febrile seizures, glycosylated hemoglobin measurement in the management of diabetes, and slow release theophylline in the management of asthma. The questionnaire was completed by 156 pediatricians. Of the 110 pediatricians who cared for diabetics, 73% used glycosylated hemoglobin measurement; of the 145 who saw patients with febrile seizures, 77% prescribed the continuous use of phenobarbital (if they used it at all); and, of the 152 pediatricians who cared for asthmatics, 86% reported using slow-release theophylline. The characteristics significantly associated with using the innovations were board certification, group rather than solo practice, teaching, medically related publications, academic appointment, younger age, and caring for a greater number of patients per week. For two of the innovations, discussion with a colleague was the most important source of information leading to a change of practice. The subjects cited local specialists as the colleagues who most often sparked the adoption of an innovation.

To determine whether intravenous immunoglobulin (IVGG) would be an efficacious adjunct in the treatment of childhood minimal change nephrotic syndrome (MCNS), we enrolled ten patients with frequently relapsing or steroid-dependent MCNS in a double-blind crossover clinical trial. At the time of relapse of the nephrotic syndrome, patients were assigned to treatment with a single outpatient infusion of IVGG (800 mg/kg) or intravenous albumin as a control. The relapse was treated concurrently with standard doses of oral prednisone. At the time of the next relapse, patients who had first received IVGG were treated with albumin, and vice versa. There were no significant differences in the length of remission between the IVGG and albumin treatments. The study had a power of 0.72 to detect a true difference of 45 days between the two therapies. We conclude that in the dose of drug used in this trial, administered at the time of relapse in conjunction with prednisone therapy to children with frequently relapsing or steroid-dependent MCNS, IVGG does not lead to a clinically important extension of the period of remission.

Anticonvulsant therapy was discontinued in 68 children with epilepsy who had had no seizures for four years, in an attempt to find the risk of relapse and the factors predictive of recurrence. In this population the probability of remaining free of seizures for four years after discontinuation of medication was 69 per cent. Children were more likely to have recurrent seizures if they were mentally retarded, if their seizures had begun before two years of age, if they had had many generalized seizures before control, or if they had had a definitely abnormal electroencephalogram before medication was discontinued. Multivariate analysis showed that the best predictors of outcome were the electroencephalogram taken at cessation of medication and the number of seizures before control. We conclude that in the normal child who has not had many seizures and whose electroencephalogram is normal or mildly abnormal, the risks of discontinuing medication after four seizure-free years are acceptable.

Hepatic veno-occlusive disease (HVOD) and interstitial pneumonitis (IP) are both widely regarded as toxicities of intensive cytoreductive therapy, but their association has not been previously examined. Risk factors for IP were evaluated in 154 patients given intensive cytoreductive therapy followed by allogeneic bone marrow transplantation during a 2 1/2 year period. IP occurred in 68 patients; HVOD occurred in 39. The actuarial incidence of IP in patients with VOD was 71% and 45% in those without VOD (p = 0.0002). In multivariate analysis, the diagnosis of hematologic malignancy (p less than 0.001), the occurrence of HVOD (p less than 0.01), and pretransplant CMV seropositivity (p less than 0.02) were significantly associated with IP. The individual relative risks for IP of presence to absence of these factors was 4.5 for the diagnosis of hematologic malignancy, 2.1 for HVOD, and 1.9 for CMV seropositivity. Pulmonary veno-occlusive disease (PVOD), a previously rare observation, was noted at autopsy in 1/5 (20%) patients with HVOD alone, 6/20 (30%) patients with IP alone, and 10/14 (71%) of patients with both HVOD and IP. The association of HVOD and IP is supportive of the concept that toxic effects of cytotoxic therapy have a major role in pathogenesis of HVOD and IP.

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.

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.

This study was undertaken to determine if there was any correlation between the estrogen receptor status and the response of patients with operable carcinoma of the breast to adjuvant chemotherapy. Seventy-seven patients with metastases to the axillary lymph nodes who were receiving adjuvant chemotherapy following a modified radical mastectomy were studied. During the period of study, 12 of 34 estrogen receptor-positive tumors recurred, with a mean disease-free interval of 17.8 months, and 19 of 43 estrogen receptor-negative tumors recurred, with a disease-free interval of 15.2 months. Statistical analysis of recurrence at two years showed no difference between these two groups. Only one patient of 18 in the premenopausal group of women with estrogen receptor-positive tumors, however, had a recurrence compared with 11 of 24 patients with estrogen receptor-negative tumors. This difference was highly statistically significant, p greater than 0.0005. We have concluded that the estrogen receptor status is not a reliable indicator of response to adjuvant chemotherapy for all patients. Our data do indicate a positive correlation between response to adjuvant chemotherapy and estrogen receptor status in the premenopausal group of patients and suggest that adjuvant chemotherapy in the premenopausal group of patients may be exerting some of its effect by ovarian suppression rather than by solely cytotoxic effect on cancer cells of the breast.

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 value of the addition of beta-blockers to coronary vasodilator therapy in the treatment of patients with unstable angina at rest is controversial. We conducted a double-blind, randomized, placebo-controlled 4 week trial of propranolol in 81 patients with unstable angina, 39 of whom were assigned to placebo and 42 of whom received propranolol in a dose of at least 160 mg daily. All patients were also treated with coronary vasodilators, including 80 mg nifedipine daily and long-acting nitrates. The incidences of cardiac death, myocardial infarction, and requirement for bypass surgery or coronary angioplasty did not differ between the two groups (propranolol = 16; placebo = 18). The propranolol group had a lower cumulative probability of experiencing recurrent resting angina than the placebo group (p = .013), and over the first 4 days of the trial the mean number of clinical episodes of angina (propranolol 0.9 +/- 0.2, placebo 1.8 +/- 0.3, p = .036), duration of angina (propranolol 15.1 +/- 4.3 min, placebo 38.1 +/- 8.4, p = .014), and nitroglycerin requirement (propranolol 1.1 +/- 0.3 tablets, placebo 3.5 +/- 0.8, p = .003) were also fewer. Continuous electrocardiographic recording for ischemic ST segment changes revealed fewer daily ischemic episodes in the propranolol group (2.0 +/- 0.5) than in the placebo group (3.8 +/- 0.7, p = .03), and a shorter duration of ischemia (propranolol 43 +/- 10 min, placebo 104 +/- 28 min, p = .039). Thus propranolol, in patients with unstable angina, in the presence of nitrates and nifedipine is not detrimental and reduces the frequency and duration of symptomatic and silent ischemic episodes.

Human lymphocytes incubated with a mouse hepatic microsomal drug metabolizing system were used to study the cytotoxicity of four anticonvulsants. In vitro toxicity assessed by trypan blue dye exclusion was significantly greater for compounds with relatively high clinical toxicity (mephenytoin and phenacemide) than those with only rare cytotoxic complications (phenytoin and phenobarbital). No toxicity occurred in the absence of microsomes and toxicity was enhanced by inhibitors of epoxide hydrolase suggesting that the cytotoxicity of the drugs may result from arene oxide metabolites. In vivo, the covalent binding of such metabolites to cell macromolecules could lead to cell death and, by acting as haptens, to secondary hypersensitivity reactions. The method may be useful in assessing the potential of a drug for toxicity, the mechanism of cell damage and individual differences in cell defenses within the human population.

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.

The performance and verbal IQ scores for the WPPSI and WISC-R were compared for two groups of children aged 5 to 8 1/2 years, one normal and one specifically language delayed (SLD). There 34 to 38 children in each group. In accordance with selection procedures, performance IQ scores were not significantly different across the two groups. Both verbal and full scale IQ were significantly lower for the SLD than for the normal group. Profiles of verbal subtest scores differed for normal and SLD children but profiles for performance subtest scores did not. Variability of performance subtest scores was not greater for the SLD than for the normal children. The results do not support the hypothesis that language delay in children is related to a nonverbal cognitive deficit.

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.

Disadvantaged pregnant black teenagers have a higher proportion of low-birth-weight infants and their offspring have a lower mean birth weight. One hundred and fifty-seven pregnant adolescents enrolled in a Baltimore public school for pregnant teenagers were studied to determine the impact of a nutritional supplement on pregnancy outcome. Seventy-eight students voluntarily agreed to receive a nutritional supplement; 79 comparably matched students did not receive the supplement. The supplement Sustacal provided a mean intake of 8691 cal with 530 g of protein and additional vitamins and minerals over an average period of 15.1 weeks. This supplement was associated with a significant increase of 157 g in the mean infant birth weight (P less than 0.05). A significant increase in infant birth weight of 269 g was noted in the offspring of supplemented girls below 16 years of age compared with the nonsupplemented girls below this age (P less than 0.05). Significant differences in infant birth weight were also noted in the offspring of nonsmoking supplemented adolescents (P less than 0.05). The proportion of low-birth-weight infants was decreased in the supplemented subjects, but the difference was not significant.

Survival, subsequent myocardial infarction and current anginal status were determined for 90 nearly consecutive patients who underwent coronary arteriography at the Johns Hopkins Hospital between 1960 and 1967. All patients had at least one coronary arterial narrowing equal to or greater than 70 percent; 78 of 90 patients would be candidates for coronary bypass surgery by present criteria. Twenty-nine of the 78 surgically "suitable" patients died of cardiac causes; 7 of 49 survivors sustained an acute myocardial infarction (mean follow-up period 9.9 years). Patients with a 70 percent or greater narrowing proximal to the first septal branch of the left anterior descending coronary artery had a significantly greater mortality compared with patients with equivalent narrowing distal to the first septal branch or with patients without 70 percent or greater narrowing of the left anterior descending artery. The patients with a 70 percent or greater narrowing of the left anterior descending artery who died were those with a significant narrowing in at least one other major coronary artery. Multivariate stepwise discriminate function analysis of all clinical, electrocardiographic (except stress electrocardiographic) and arteriographic variables identified three independent predictors of mortality: (1) the simultaneous occurrence of a narrowing in left anterior descending and right coronary arteries, (2) prior myocardial infarction; and (3) 70 percent or greater narrowing proximal to the first anterior descending septal branch. When stress electrocardiographic findings were included, a "positive" stress electrocardiographic test was also an independent predictor of mortality.