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Biomedical subjects

J H Ellenberg

Publications and source records attributed to J H Ellenberg.

At least 37 records · Page 2Linked to original sources

Preclinical detection in studies of the etiology, natural history, and treatment of Parkinson's disease.

The development of reliable preclinical detection procedures for idiopathic Parkinson's disease may be the fundamental advance required for the establishment of the cause, the natural history, and ultimately, the prevention of this neurodegenerative disorder. The usefulness of these preclinical markers in efforts to better understand the etiology and development of this disorder will relate to whether they are direct measures of dopamine production or indirect measures such as metabolic changes or comorbidity, whether they can be used in the first or later decades of life, whether they are invasive, and whether they are expensive and sophisticated or simple and cheap. An overview of the criteria for evaluation of the utility of specific markers, as well as an assessment of the importance of early markers in future research, is presented.

Biomarkers↗

Preclinical markers in studies of Parkinson's disease.

The development of reliable preclinical detection procedures for idiopathic Parkinson's disease may be the fundamental advance required for the establishment of the cause, the natural history, and ultimately, the prevention of this neurodegenerative disorder. The usefulness of these preclinical markers in efforts to better understand the etiology and development of this disorder will relate to whether they are direct measures of dopamine production or indirect measures such as metabolic changes or comorbidity, whether they can be used in the first or later decades of life, whether they are invasive, and whether they are expensive and sophisticated or simple and cheap. An overview of the criteria for evaluation of the utility of specific markers, as well as an assessment of the importance of early markers in future research, is presented.

Biomarkers↗

Phenobarbital for febrile seizures--effects on intelligence and on seizure recurrence.

Phenobarbital is widely used in the treatment of children with febrile seizures, although there is concern about possible behavioral and cognitive side effects. In 217 children between 8 and 36 months of age who had had at least one febrile seizure and were at heightened risk of further seizures, we compared the intelligence quotients (IQs) of a group randomly assigned to daily doses of phenobarbital (4 to 5 mg per kilogram of body weight per day) with the IQs of a group randomly assigned to placebo. After two years, the mean IQ was 7.03 [corrected] points lower in the group assigned to phenobarbital than in the placebo group (95 percent confidence interval, -11.52 to -2.5, P = 0.0068 [corrected]). Six months later, after the medication had been tapered and discontinued, the mean IQ was 5.2 points lower in the group assigned to phenobarbital (95 percent confidence interval, -10.5 to 0.04, P = 0.052). The proportion of children remaining free of subsequent seizures did not differ significantly between the treatment groups. We conclude that phenobarbital depresses cognitive performance in children treated for febrile seizures and that this disadvantage, which may outlast the administration of the drug by several months, is not offset by the benefit of seizure prevention.

Child, Preschool↗

Prenatal and perinatal antecedents of febrile seizures.

We examined prenatal and perinatal characteristics as possible risk factors for febrile seizures in a large pediatric population. Family history was among the few identified factors that made an important contribution to vulnerability to febrile seizures; however, no more than 6% of febrile seizures could be attributed to a characteristic of family history. Maternal illness, smoking history, and a few rare neonatal characteristics were associated with increases in risk. No complication of labor or delivery was an important risk factor for febrile seizures.

Anticonvulsants↗

Clinical trials.

Broad guidelines for the design, implementation, analysis, and reporting of results of clinical trials are given. The use of randomization, concurrent controls, and blinding is justified. Basic principles of the design of clinical trials are outlined and include the areas of specification of the hypothesis, definition of the outcome and the logistics of protocol design, and safeguards to ensure its proper implementation.

Clinical Trials as Topic↗

Biostatistical collaboration in medical research.

There has been an explosive growth in the development of statistical methodology over the past several decades. Research in both medicine and public health, in which the involvement of biostatisticians has increased dramatically during this period, has been both a beneficiary of this new methodology as well as a source of new problems. The contributions of statistical methodology in design, implementation, and analysis as they relate to the role that biostatistics and biostatisticians now play in the field of medical research are addressed. We comment on: (1) the acceptance by the medical community that biostatistical concepts are an integral part of sound medical research; (2) the sometimes unrealistic expectations placed on biostatistics and biostatisticians given limited resources and/or limited control; (3) some controversies among biostatisticians; and (4) the need for emphasizing the design and implementation phases of medical investigations.

Biometry↗

Infarcts of undetermined cause: the NINCDS Stroke Data Bank.

In a prospective study of 1,805 hospitalized patients in the Stroke Data Bank of the National Institute of Neurological and Communicative Disorders and Stroke, the 1,273 with infarction were classified into diagnostic subtypes. Diagnosis was based on the clinical history, examination, and laboratory tests including computed tomography, noninvasive vascular imaging, and where safe and relevant, angiography. Five hundred and eight cases (fully 40%) were labeled as infarcts of undetermined cause (IUC), of which 138 (27%) were evaluated with both computed tomography and angiography. The clinical syndrome and computed tomographic and angiographic findings in 91 (65.9%) of these 138 IUC cases were clearly not attributable to large-artery thrombosis and could permit reclassification of the infarct as due to some form of embolism. Failure to define a source of embolus kept them in the category of IUC. Thirty-one cases (22.5%) could be reclassified as due to stenosis or thrombosis of a large artery, and 16 (11.6%) as lacunar infarction. To determine if those selected for angiography among the IUC patients differed from those with other final diagnoses, a stepwise multiple logistic model was used. The most important characteristics were young age, presence of a superficial infarct, prior transient ischemic attack, low weakness score, and presentation with a nonlacunar syndrome. The results of the model suggest that angiography use was determined by clinical characteristics uniformly across centers and not by final diagnosis. Continued use of the category IUC may help clarify risk factors and stroke subtypes, allow new mechanisms of ischemic stroke to be uncovered, and prevent classification categories of stroke used in clinical trials from becoming too broad.

Cerebral Angiography↗

The extrapolation of attributable risk to new populations.

I develop a method for extrapolation of attributable risk estimated from one population, to other populations with a different rate of risk factor exposure and/or rate of outcome. The method uses the relationship between attributable risk and the product moment correlation.

Adult↗

Cluster of perinatal events identifying infants at high risk for death or disability.

To determine the prognostic import of neonatal seizures according to the presence or absence of certain other postnatal characteristics, we studied a population of 39,000 infants with birth weight greater than 2500 gm. Children with clinically recognized neonatal seizures and 5-minute Apgar scores less than or equal to 5 and who had at least one of five signs compatible with neonatal encephalopathy had a risk for first-year death of 33%. Survivors of this cluster of events (low Apgar score-abnormal signs-seizures) had a risk for motor disability of 55%. In contrast, survivors of neonatal seizures who did not have poor Apgar scores or other abnormal signs had a risk for motor disability of only 0.13%. Thus, among infants with neonatal seizures the risk for cerebral palsy was 420 times greater if there had been a low 5-minute Apgar score and other neonatal signs. Low Apgar score-abnormal signs-seizures constituted a cluster of events that served to identify, within the first days of life, a tiny subgroup of term newborn infants in whom risk for chronic motor disability was 55%, and for death or disability was 70%.

Apgar Score↗

Toxoplasmosis: maternal and pediatric findings in 23,000 pregnancies.

An analysis of the antibody titers to toxoplasmosis for 22,845 pregnant women in the Collaborative Perinatal Project was conducted in relation to clinical and laboratory findings in the mothers and children through 7 years of age. More than 900 observations were considered for each mother and child. The major findings were in the children and included a predicted doubling in the frequency of deafness among children born to women with antibody to toxoplasmosis, a predicted 60% increase in microcephaly, and a 30% increase in low IQ (less than 70) in association with the presence of high maternal antibody titer (256 to 512) to toxoplasma. A serologically defined high-risk group of mothers was identified on the basis of high indirect hemagglutination antibody levels or seroconversions and increased IgM toxoplasma antibody levels (indirect fluorescent antibody greater than or equal to 32, enzyme-linked immunosorbent assay greater than or equal to 0.7). Of the 15 pregnancies in this group, two children had congenital toxoplasmosis and three were stillborn.

Antibodies↗

Migraine and other diseases in women of reproductive age. The influence of smoking on observed associations.

From among the pregnant women in the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, we identified 508 who had migraine, and 3192 who had no history of migraine, of taking headache medication during the previous 12 months, and of headaches during the pregnancy. Migraineurs smoked more heavily and had a longer smoking history than their headache-free peers. Among migraineurs, smokers were not more likely to consume analgesics than nonsmokers. Regardless of smoking classification, more migraineurs consumed tranquilizers, amphetamines, and sleeping pills than headache-free women. Among smokers only, migraine was associated with heart disease, thrombosis/phlebitis, asthma, peptic ulcer, and pneumonia. In nonsmokers, migraine was associated with drug sensitivity and other allergies.

Adolescent↗

The asymptomatic newborn and risk of cerebral palsy.

We investigated whether infants weighing over 2500 g who had experienced one or more of 14 late pregnancy or birth complications, but who were free of certain signs in the nursery period were at increased risk of cerebral palsy (CP). The signs evaluated were decreased activity after the first day of life, need for incubator care for three or more days, feeding problems, poor suck, respiratory difficulty, or neonatal seizures. More than 90% of the infants weighing over 2500 g had none of these signs. In asymptomatic infants with one or more birth complications, the rate of CP by 7 years of age was 2.3/1000; among asymptomatic infants whose births were uncomplicated, the rate of CP was 2.4/1000. The risk for CP rose with number of abnormal neonatal signs, and children with sustained neonatal abnormalities were at higher risk than those whose abnormalities were transient. Most children with CP did not derive from groups at increased risk. The full-term infant whose birth was complicated but who was free of certain abnormal signs in the newborn period was not at increased risk of CP.

Apgar Score↗

Predisposing and causative factors in childhood epilepsy.

We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one nonfebrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.

Brain Ischemia↗

Antecedents of cerebral palsy. Multivariate analysis of risk.

We examined prenatal and perinatal factors predicting cerebral palsy, using multivariate analysis to investigate which factors were most important and the proportion of cases for which they accounted. Maternal mental retardation, birth weight below 2001 g, and fetal malformation were among the leading predictors. Breech presentation was also a predictor, but breech delivery was not. A third of the children with cerebral palsy who had breech presentations had a major noncerebral malformation. Among 189 children with cerebral palsy, 40 (21 percent) had at least one of three clinical markers suggestive of asphyxia; only 17 of these 40 children (9 percent of all cases) lacked major congenital malformation or other intrinsic defects that might have contributed to an unfavorable outcome. When all the principal risk factors present by the time labor began were considered, the 5 percent of the population at highest estimated risk was seen to have contributed 34 percent of the cases. When all the risk factors present during the period beginning before pregnancy and extending through the nursery stay were included, the 5 percent at highest risk was seen to have contributed 37 percent of the cases. Thus, the inclusion of information about the events of birth and the neonatal period accounted for a proportion of cerebral palsy only slightly higher than that accounted for when consideration was limited to characteristics identified before labor began.

Analysis of Variance↗

Do seizures in children cause intellectual deterioration?

We studied whether the occurrence of seizures in childhood affected intellectual performance. We compared the full-scale IQs at seven years of age of children who had experienced one or more nonfebrile seizures with the IQs of their seizure-free siblings who were tested at the same age in a large longitudinal study. Among 98 children with seizures, the mean score on IQ tests at seven years was not significantly different from the mean score of their siblings. Mental retardation was more common among the children with seizures, but the excess was accounted for by children who had neurologic abnormalities before the first seizure. We also examined the IQ before and after the onset of seizures in 62 children whose first seizure occurred in the interval between psychometric examinations given at four and seven years of age. The IQ at seven years in the children with seizures did not differ significantly from that in controls matched for IQ (as determined at the four-year assessment), sex, race, and socioeconomic status. Thus, in both the sibling-control comparison and the comparisons made between controls and subjects before and after the onset of seizures, the occurrence of nonfebrile seizures was not associated with a significant change in full-scale IQ.

Anticonvulsants↗

Survey on the management of febrile seizures.

A survey regarding the management of the child with febrile seizures was mailed to 10 000 child neurologists, neurologists, pediatricians, and family and general practitioners. The response rate varied by specialty; overall, slightly more than half the physicians responded. One third or less of physicians prescribed anticonvulsive therapy only at the time of febrile illness, although this practice was much less common among recent graduates. If children had lengthy or focal seizures, the majority of physicians in all specialties either prescribed long-term treatment or referred for consultation. Long-term daily anticonvulsant therapy was prescribed most frequently by child neurologists and least often by general practitioners, who most often referred for consultation. Rate of hospitalization also differed according to specialty. The results of the survey indicate that the management of a child with febrile seizures may differ depending on the specialty of the attending physician.

Anticonvulsants↗

Antecedents of seizure disorders in early childhood.

One or more nonfebrile seizures occurred between the ages of 1 month and 7 years in eight per 1000 white and in nine per 1000 black children enrolled in a large prospective study. We examined hundreds of prenatal and perinatal factors as predictors of childhood seizure disorders. Congenital malformations of the fetus (cerebral and noncerebral), family history of certain neurologic disorders, and neonatal seizures were the major predictors identified. Forty percent of children with postneonatal seizures and 68% of children with minor motor seizures had one or more of these risk factors compared with 21% of the seizure-free population. More than half of the children with minor motor seizures and a third of the infants with neonatal seizures had congenital malformations. Based on the prenatal and perinatal factors examined, prediction of postneonatal seizures carried a high rate of false-positive identification, indicating that our knowledge of the etiology of childhood seizure disorders is still very limited.

Child↗

Predictors of low and very low birth weight and the relation of these to cerebral palsy.

In a large prospective study, we investigated predictors of moderately low (1,501 to 2,500 g) and very low (less than 1,501 g) birth weight. Maternal age, height, and socioeconomic status, related to moderately low birth weight on univariate analysis, were not on multivariate analysis significant predictors for either low-birth-weight outcome. The leading predictors of very low birth weight were low weight (less than 2,000 g) of last live birth, fetal malformation, nonwhite race, early vaginal bleeding, cigarette smoking, and chorionitis. Some of these were also predictors of moderately low birth weight. About 20% of births under 1,501 g could be attributed to chorionitis, a characteristic of less than 3% of the births. Of the major predictors of low birth weight, only prolonged rupture of membranes, chorionitis, and congenital malformations contributed to the risk of cerebral palsy beyond their contribution to the risk of low birth weight.

Cerebral Palsy↗