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Biomedical subjects

M J Painter

Publications and source records attributed to M J Painter.

At least 19 recordsLinked to original sources

Specialty care by child neurologists: a workforce analysis.

OBJECTIVE: To provide a current profile of the practice of child neurology, report the attitudes of child neurologists toward practice, and analyze the supply of child neurologists. METHODS: In March 2002, a questionnaire was sent to all active members of the Child Neurology Society (n = 1,051) and to nonmember physicians under age 70 who listed child neurology as a primary or secondary specialty on the American Medical Association Masterfile (n = 433). The response rate was 65%. Eligibility criteria were then applied to arrive at the sample of main specialty in child neurology working at least 20 hours per week in patient care. The final population was 604. Differences in practice characteristics were tested by practice type, and the number of full-time patient care child neurologists was projected by extrapolating to nonrespondents. RESULTS: There are 904 full-time patient care child neurologists in the United States and 1.27 per 100,000 children. Career satisfaction is 90%, yet no growth in the supply is projected over the next 20 years. Wait times for an appointment average 53 and 44 days for a new and return visit, with longer wait times in university settings. Average annual income is 151,000 dollars. CONCLUSION: The practice characteristics of child neurologists suggest that the specialty will be challenged to meet patient demands.

Adult↗

Phenobarbital compared with phenytoin for the treatment of neonatal seizures.

BACKGROUND: Seizures occur in 1 to 2 percent of neonates admitted to an intensive care unit. The treatment is usually with either phenobarbital or phenytoin, but the efficacy of the two drugs has not been compared directly. METHODS: From 1990 to 1995, we studied 59 neonates with seizures that were confirmed by electroencephalography. The neonates were randomly assigned to receive either phenobarbital or phenytoin intravenously, at doses sufficient to achieve free plasma concentrations of 25 microg per milliliter for phenobarbital and 3 microg per milliliter for phenytoin. Neonates whose seizures were not controlled by the assigned drug were then treated with both drugs. Seizure control was assessed by electroencephalographic criteria. RESULTS: Seizures were controlled in 13 of the 30 neonates assigned to receive phenobarbital (43 percent) and 13 of the 29 neonates assigned to receive phenytoin (45 percent; P=1.00). When combined treatment is considered, seizure control was achieved in 17 (57 percent) of the neonates assigned to receive phenobarbital first and 18 (62 percent) of those assigned to receive phenytoin first (P=0.67). The severity of the seizures was a stronger predictor of the success of treatment than was the assigned agent. Neonates with mild seizures or with seizures that were decreasing in severity before treatment were more likely to have their seizures end, regardless of the treatment assignment. CONCLUSIONS: Phenobarbital and phenytoin are equally but incompletely effective as anticonvulsants in neonates. With either drug given alone, the seizures were controlled in fewer than half of the neonates.

Anticonvulsants↗

Bovine spongiform encephalopathy and new variant Creutzfeldt-Jakob disease: an overview.

About 10 years after bovine spongiform encephalopathy (BSE) appeared in British cattle, a new variant of Creutzfeldt-Jakob disease (nv-CJD) was described in the United Kingdom. This new disease is distinguishable from classical CJD in its aetiology, epidemiology, clinical profile, and neuropathology. The emergence of nv-CJD raised fears of a causal relationship between BSE and nv-CJD and of a human epidemic of indeterminate size. This paper reviews our knowledge of this group of diseases, and examines recent scientific evidence, which indicates that BSE is indeed the source of nv-CJD, and discusses the public health implications.

Animals↗

Infusion of intrathecal baclofen for generalized dystonia in cerebral palsy.

UNLABELLED: Generalized dystonia occurs in 15 to 25% of persons with cerebral palsy (CP) and responds poorly to medical and surgical treatments. OBJECT: After the authors observed a woman whose dystonic CP was dramatically improved by continuous infusion of intrathecal baclofen, they designed this pilot study to evaluate the effect of this treatment on a group of patients with dystonic CP. METHODS: The authors assessed the short-term response to intrathecal baclofen infusion in 12 patients with dystonic CP. An intrathecal catheter was inserted percutaneously and connected to an external microinfusion pump. The infusion began at a rate of 100 microg/day and was increased by 50 microg every 12 hours until the dystonia abated, adverse effects occurred, or the dose reached 900 microg/day with no improvement. Two observers, one blinded and one not blinded to the patient's treatment status, viewed videotapes made before and after the infusions and graded the dystonia in eight body regions, using a 5-point scale. Overall and regional scores were compared by using Wilcoxon signed-rank tests. CONCLUSIONS: Dystonia diminished in 10 of 12 patients whose average daily dose of intrathecal baclofen was 575 microg. Overall dystonia scores and scores for the extremities, trunk, and cervical regions were significantly better after infusion (p = 0.003). The two observers' scores were not significantly different. Programmable infusion pumps were subsequently implanted in eight patients for long-term therapy and improvement was sustained in six (p < 0.05). Intrathecal baclofen infusion is a promising treatment option for generalized dystonia associated with CP. The effects of intrathecal baclofen infusion on dystonia can be evaluated by using short-term continuous infusions.

Adolescent↗

Inherited unbalanced subtelomeric translocation in a child with 8p- and Angelman syndromes.

A 10 1/2-month-old boy was found to have an unbalanced karyotype, 45,XY,der(8)t(8;15) (p23.3;q13). One of 83 analyzed cells also contained an unidentified small marker. Fluorescence in situ hybridization (FISH) using cosmid probes for SNRPN, D15S10, and GABRB3 for the Prader-Willi syndrome (PWS)/Angelman syndrome (AS) critical region were not present on the derived chromosome. The child had some physical findings compatible with monosomy 8p. The mother also was a balanced carrier for the translocation. She also had 2/80 cells with an additional small marker chromosome, similar in size to the extra chromosome in the one cell of the propositus. FISH using an 8 paint did not show the reciprocal exchange on the der(15) but was demonstrated by using an 8p telomeric probe. At 18 months of age the child has some manifestations of AS. Earlier diagnosis may have been masked by the 8p- phenotype, or related to difficulty in diagnosing AS in infants.

Angelman Syndrome↗

Natural history, prognosis, and lipid abnormalities of idiopathic ischemic childhood stroke.

A study was performed to assess the natural history, prognostic factors, and lipid and apolipoprotein abnormalities of idiopathic ischemic childhood stroke. A case series of 42 children, retrospectively identified with idiopathic ischemic strokes, were reassessed an average of 7.4 years (range, 1 to 19 years) after presentation. Patients were interviewed and examined, and fasting serum was obtained for lipid and apolipoprotein analysis. Poor outcome was defined as moderate to severe hemiparesis, special educational needs, epilepsy, recurrent stroke, or stroke-related death. Eighteen (43%) of the patients had a poor outcome. Among them were moderate to severe hemiparesis in 14 (78%), recurrent strokes in seven (39%), and one death. Poor outcome was evident early in their clinical course. Independent of outcome, lipid abnormalities including an elevated triglyceride and low-density lipoprotein cholesterol, and a depressed high-density lipoprotein cholesterol were seen in one third of all patients. A depressed ratio of apolipoprotein A-1 to apolipoprotein B (using adult normative values) was seen in half of the entire cohort. Clinical features of children with unexplained ischemic strokes at presentation and their subsequent course are described. Significant risk factors for a poor outcome include (1) persistence of hemiparesis 1 month after the stroke, (2) cortical as opposed to subcortical location, and (3) bilateral occlusive disease with telangiectasia on cerebral angiography. Previously described risk factors for an unfavorable prognosis, including occurrence during infancy and presentation with seizures, were not substantiated. Lipid abnormalities occur at an increased frequency in children after unexplained ischemic strokes. Prospective assessment of lipoprotein profiles are needed to further assess clinical significance. Assessing apolipoproteins may provide further insight than lipid values alone.

Adolescent↗

Animal models of perinatal asphyxia: contributions, contradictions, clinical relevance.

Animal models have contributed immensely to our understanding of hypoxic ischemic encephalopathy in the newborn. A number of animal models have been used, including both primate and subprimate species. Although the Rhesus monkey model has a dramatically similar pathological distribution of brain injury when compared with the human, other pathologic processes secondary to asphyxia may be more appropriately assessed in other species. The maxim that because primates are closer on the phylogenetic tree to humans than are subprimates all observations in the primate are applicable to the human is simply not true. Understanding of the neurochemical consequences of asphyxia in the past decade have arisen from experiments primarily in the neonatal rat. We have come to understand that not only is the hypoxic event of major significance, but that, once reperfused, reoxygenation causes further injury. Free-radical generation following reperfusion may be massive and may further contribute to cell membrane injury. These observations have lead to rational theoretic approaches to the treatment of hypoxic ischemic brain injury. On the other hand, previously used treatments such as osmotic agents and glucocorticoids would appear to be not only inefficacious but hazardous in the treatment of hypoxic ischemic brain injury. The role of nitric oxide (NO) in the pathogenesis of brain injury is yet uncertain, but there is little doubt that it plays a significant role. Although survival of the immature animal subjected to hypoxic environment is longer than in the mature animal, the central nervous system of the immature animal is more sensitive to glutamate and N-Methyl-D-aspartate (NMDA) receptor-mediated injury.

Acidosis, Respiratory↗

Hepatitis B outbreak in a drug trials unit: investigation and recommendations.

In autumn 1990 three young men developed acute hepatitis B. They belonged to a group of 24 young male volunteers who had taken part in a trial in a residential unit for drug trials in July and August 1990. A further case of acute hepatitis B and a carrier of hepatitis B e antigen (HBeAg) were detected by serological testing of the volunteers. Volunteers, in two groups of twelve, had occupied the unit at different times during the trial. The four cases occurred in the group that contained the HBeAg positive carrier. The carrier had also taken part in two trials on the unit in 1989. He was HBeAg positive then, but transmission of hepatitis B virus (HBV) did not occur. Although blood samples were taken in each of the three trials, intravenous cannulas were used only in the 1990 trial. It is likely that HBV was transmitted by blood to blood contact between volunteers when blood was sampled through cannulas during the trial. This outbreak might have been prevented. If an infection control policy had been applied to avoid hazardous practices, and volunteers had been screened for HBV before entry and the carrier excluded (as recommended by the Association of Independent Clinical Research Contractors), the outbreak would not have occurred. Volunteers for drug trials in residential units should be screened for HBV, human immune deficiency virus (HIV) and hepatitis C virus (HCV), and those found to be infected should not be accepted.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

Neonatal phenobarbital and phenytoin binding profiles.

Phenobarbital and phenytoin binding profiles were determined in 27 neonates. Binding of both drugs decreased compared with that in older subjects. In vitro binding of both agents correlated significantly with total protein and albumin concentrations. In vivo binding at 0.5 hours correlated significantly with birthweight and gestational age. Phenobarbital, but not phenytoin, binding decreased when three other therapeutic agents were concomitantly administered. Bilirubin concentrations, free fatty-acid concentrations, and pH values encountered in this population did not significantly influence binding. An in vitro binding profile accurately predicted in vivo free fractions (percent drug unbound) and plasma concentrations of both drugs.

Birth Weight↗

Electrographic seizures in preterm and full-term neonates: clinical correlates, associated brain lesions, and risk for neurologic sequelae.

Electrographically confirmed seizures in preterm and term neonates were compared with respect to clinical correlates, incidence, associated brain lesions, and risk for neurologic sequelae. Over a 4-year period, 92 neonates from a neonatal intensive care unit population of 4020 admissions at a large obstetric hospital with 40,845 livebirths had electrographically confirmed seizures. Sixty-two neonates were preterm and 30 were full-term for gestational age. Chi-square calculations were used to compare the two groups. While the incidence of seizures for all neonates admitted to a neonatal intensive care unit was 2.3%, outborn neonates were more likely to have seizures than inborn neonates. Preterm neonates of < or = 30 weeks gestational age had a seizure frequency of 3.9%, which was significantly higher than that of older preterm neonates and full-term neonates. Clinical criteria contemporaneous with electrographic seizures were noted in only 28 (45%) of 62 preterm, and 16 (53%) of 30 full-term neonates. Subtle seizures coincident with electrographically confirmed seizures were the most predominant clinical type for both term and preterm neonates (71% and 68%, respectively). The distribution of clonic, myoclonic, and tonic seizures was also similar for both groups. Autonomic signs coincident with electrographically confirmed seizures (ie, blood pressure, heart rate, oxygenation, respiration changes) were more frequently observed in preterm than full-term neonates with subtle seizures; 7 (37%) of 19 compared with 1 (6%) of 16. Electrical seizures without clinical correlates were noted more frequently than electroclinical seizures for both populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticonvulsants↗

Neonatal seizures: diagnosis and treatment.

Neonatal seizures are a frequent problem encountered in neonatal nurseries, but their significance is controversial. Some investigators regard newborn seizures as simply epiphenomena and reflective of brain injury, whereas others note associated metabolic and physiologic aberrations suggesting that seizures per se are injurious to the central nervous system. The proper approach to the treatment of neonatal seizures depends on the etiology because treatment differs if seizures are of metabolic, toxic, or structural origin. Most studies reporting the efficacy of anticonvulsant agents neither define the seizure characteristics being treated nor use electroencephalographic documentation of seizure activity. The choice of anticonvulsants has been based on tradition rather than on the proven superiority of one agent over another. Although several anticonvulsants are available, phenobarbital remains the drug most frequently chosen as the initial agent in treatment. The important pharmacologic considerations of anticonvulsants include route of administration, ability to achieve therapeutically efficacious and predictable plasma levels rapidly, drug distribution, the availability and affinity of receptor sites, protein-binding characteristics, effects on brain growth, and cardiovascular toxicities. At the present time, critical questions remain regarding the effects of both seizures and anticonvulsants on the developing central nervous system.

Electroencephalography↗

Destructive brain lesions of presumed fetal onset: antepartum causes of cerebral palsy.

Antepartum events have been associated with fetal brain injury and may contribute to later neurological sequelae. However, children with these injuries may be asymptomatic or exhibit few clinical signs during the neonatal period. Six neonates are presented with destructive brain lesions of fetal onset based on radiological and neurophysiological studies at birth. No intrapartum difficulties were noted in any of the cases. Two maternal histories were significant for either placental bleeding or toxemia during the second or third trimesters of pregnancy. Fetal porencephaly from presumed intraventricular hemorrhage was documented by serial abdominal sonography for these two children. No causes could be assigned for the remaining four patients with destructive brain lesions. All six children had normal results on neurological examinations at birth, although four neonates later presented with isolated seizures at 8 to 30 hours of life which resolved after administration of anti-epileptic medication. In all cases initial neonatal electroencephalographic records showed abnormalities consisting of major background asymmetries or seizures. Initial documentation of cerebral lesions was made by fetal sonography (two patients) and computed tomography scan (four patients) during the initial 30 hours of life, timing the lesions to the antepartum period. Cerebral palsy has been documented in all children; one child had resolution of her deficits by 6 months of age. Better surveillance of events during the antepartum period may help identify specific pathophysiological conditions that contribute to cerebral palsy. Neurophysiological and imaging studies should be used during the immediate new-born period for neonates believed to have cerebral lesions based on maternal sonography or isolated seizures.

Brain Diseases↗

Secondary cases of meningococcal infection among close family and household contacts in England and Wales, 1984-7.

To determine the incidence of secondary meningococcal infection in close family and household contacts of index patients and to review the efficacy of chemoprophylaxis the records of 3256 cases occurring from 1984 through 1987 were examined. Seventeen secondary cases (0.5%) of infection were identified among these groups. The median interval between index and secondary cases was seven weeks. Fourteen secondary cases occurred more than one week after the disease was diagnosed in the index case. Three secondary cases had not received chemoprophylaxis and in another case the infecting strain had acquired resistance to rifampicin. Prophylaxis for the close contacts of 10 out of 11 of the remaining index patients failed to fulfil all the criteria of an optimal regimen. Even after optimal chemoprophylaxis the medical practitioner and the family should be aware of the increased and prolonged risk of secondary meningococcal infection among close contacts of patients with the disease.

Adult↗

Controversies concerning neonatal seizures.

Five issues are discussed with respect to the diagnosis, etiology, treatment, prognosis, and pathogenesis of neonatal seizures. The presentation of a newborn with seizures represents a true emergency and frequently indicates significant neurologic dysfunction or damage to the immature nervous system. Despite the urgency to establish a diagnosis, several unique aspects of neonatal seizures impede prompt recognition. In addition, several etiologic possibilities may be associated with seizures. The efficacy of antiepileptic drugs and the prediction of outcome of patients with neonatal seizures are controversial. Experimental research in developing animals suggests both a selective vulnerability and resistance of the brains of immature animals subjected to neonatal seizures.

Asphyxia Neonatorum↗