Edwin L. Zalneraitis

Immunocytochemical studies of substance P and leucine-enkephalin in Huntington's disease

The distribution of substance P and leucine-enkephalin in selected regions of brain obtained postmortem from patients with Huntingtons disease and from neurologically normal persons has been studied with immunocytochemical techniques. In the normal brain, substance P immunoreactivity was identified in medium-sized neurons in the neostriatum, in neurons of the external segment of the globus pallidus, and in fine fibers in teh neostriatum, inner segment of the globus pallidus, and in the pars reticulata of the substantia nigra. Huntingtons disease brains all exhibited a marked decrease in substance P fiber density in the substantia nigra and globus pallidus. A few medium-sized neurons with substance P immunoreactivity remained in the neostriatal remnant. Leucine-enkephalin immunoreactive processes were present throughout the neostriatum of normal brain, and were densely packed in the external segment of the globus pallidus and in the substantia nigra. A uniform population of medium-sized neurons containing immunoreactive leucine-enkephalin was present in the caudate and putamen. By contrast, in the Huntingtons disease brains there was a marked diminution of fiber staining in the globus pallidus and substantia nigra. A few medium-size neurons and sparse fibers with leucine-enkephalin immunoreactivity persisted in the atrophic neostriatum. These observations are consistent with previous reports of regional peptide concentrations in both normal and Huntingtons disease brain. Cells containing substance P and leucine-enkephalin immunoreactivity persist in the basal ganglia in brains from patients with Huntingtons disease, and we have no evidence that cellular content of one or the other peptide is associated with disproportionate cell death or survival.

Pediatric Residency Duty Hours Before and After Limitations

OBJECTIVES. The goals were to examine pediatric resident and program director experiences implementing the Accreditation Council for Graduate Medical Education work hour limits and to compare duty hours, moonlighting, and fatigue before and after the limits became effective. METHODS. National random samples of 500 pediatric residents who graduated in 2002 and in 2004 were surveyed to compare resident duty hours and fatigue before and after the Accreditation Council for Graduate Medical Education limits were implemented. In addition, all US pediatric residency program directors were surveyed at the end of the 2003/2004 academic year, to provide a complementary retrospective examination of limit implementation. RESULTS. Totals of 65%, 61%, and 83% of 2002 residents, 2004 residents, and program directors, respectively, responded. The proportion of residents who reported working >80 hours per week declined from 49% for NICU/PICU rotations before the limits to 18% after limit implementation. Resident well-being was the factor identified most often by both residents and program directors as being improved since the limitations. Multivariate modeling also showed reductions in the proportions of residents who reported falling asleep while driving from work or making errors in patient care because of fatigue. Overall, 89% of pediatric residents and program directors reported that the current system is effective in ensuring appropriate working hours. CONCLUSIONS. Since the Accreditation Council for Graduate Medical Education duty hour limits went into effect, pediatric residents report working fewer hours and making fewer patient care errors because of fatigue. Although room for additional improvement remains, the experiences of residents and program directors suggest that implementation of the Accreditation Council for Graduate Medical Education limits in pediatric residency programs is improving resident well-being.

The State of Pediatrics Residency Training: A Period of Transformation of Graduate Medical Education

Graduate medical education is in a period of transformation. This article reviews the state of pediatrics residency training by summarizing the changing demographics within training programs, examining the new educational paradigm with an emphasis on competency-based education and continuous professional development, and describing forces influencing the workplace and the focus on work-life balance. Strategies are suggested for leaders in graduate medical education to meet the challenges experienced during this period of transformation.

Primary lateral sclerosis in a child

Primary lateral sclerosis (PLS), previously undescribed in children, is characterized by a spastic motor deterioration and pathologic demonstration of corticospinal tract degeneration. We report an infant who, before 12 months of age, developed a progressive motor disease characterized by generalized spasticity. He died at 47 months, and neuropathologic examination revealed only corticospinal tract degeneration. We conclude that this child had typical clinical and pathologic findings for PLS.

Disseminated neonatal hemangiomatosis: Successful hepatic resection with subsequent development of hydrocephalus

This is a report of an infant with cutaneous hemangiomas who underwent successful resection of an extensive hemangioma of the liver as well as multiple intestinal hemangiomas. Later, he developed hydrocephalus due to a cerebellar cystic hemangioblastoma. This case documents the usefulness of cranial computed tomography (CCT) in determining the extent of involvement in disseminated neonatal hemangiomatosis.

Cerebral blood flow and EEG changes in preterm infants with patent ductus arteriosus

It is unknown whether the decreased cerebral blood flow seen in infants with a large patent ductus arteriosus is associated with cerebral dysfunction. Decreased cerebral blood flow in adult human and animal models has been associated with altered electroencephalography (EEG), spectral-analyzed EEG, and EEG response to photic stimulation. Cerebral blood flow velocity, EEG, spectral analysis of EEG, and photic alteration of EEG spectra were evaluated in 8 infants before and after closure of a significant patent ductus arteriosus and in 10 control infants without a patent ductus arteriosus. All infants with patent ductus arteriosus had moderate or large shunts associated with a 25% mean reduction in cerebral blood flow velocity. There were no differences, however, in EEG, spectral analysis of EEG, or photic alteration of the spectral analysis for these infants before and after patent ductus arteriosus closure as compared to controls. It is concluded that the degree of decreased cerebral blood flow in infants with a significant patent ductus arteriosus is not sufficient to cause measurable alteration in electrocortical activity.

Benign transient downward gaze in preterm infants

Five preterm infants who had episodes of conjugate downward gaze 2-3 months after birth were evaluated. Three were extremely preterm, born at 22-25 weeks gestation, and 2 were twins, born at 28 weeks gestation. In all patients, multiple, brief episodes of downward gaze occurred daily, with each lasting for several seconds. In 3 infants, downward gaze occurred more often with stimulation, while in another it occurred more frequently prior to feeding. There was never an associated change in vital signs, level of consciousness, muscle tone, or focal neurologic deficit. All infants had bronchopulmonary dysplasia. Neuroimaging studies were normal in 3 patients and demonstrated nonspecific abnormalities in 2. At follow-up (6 1/2-34 months corrected age), intermittent downward gaze had completely resolved in 3 infants and was decreased in frequency and severity in the youngest 2. Four infants had normal development and neurologic examinations, while 1 child demonstrated mildly increased asymmetric muscle tone with normal development. Intermittent tonic downward gaze can be seen in extremely preterm infants who subsequently have normal development, and may represent a maturational delay in upward gaze reflex systems.

Cerebral hemorrhage in neonates with coarctation of the aorta.

Coarctation of the aorta is an uncommon cause of cerebral hemorrhage in the full- or near-term infant. The clinical, radiologic, and neurologic findings of four infants with aortic coarctation and cerebral hemorrhage are presented. In all four infants, cerebral hemorrhage was associated with only moderate elevation of systolic blood pressure (90-110 mmHg).

Marantic endocarditis in children and young adults: clinical and pathological findings.

The clinical and pathologic findings of 7 children and young adults with marantic endocarditis are renewed. Cerebral embolic infarction attributable to the marantic regetations occurred in 3 patients. The most common neurologic findings were altered mental status, seizures, and hemlplegia. Fire of the 7 patients had had cardiac catneterization. Sepsis, pneumonia, hypoxia, disorders of coagulation, and renal failure were frequently present in these seriously ill patients. In each instance, the diagnosis of marantic endocarditis was unsuspected and established only at autopsy.

Prediction of survival in severely asphyxiated infants

There is currently no set of evaluations that allows for the accurate prediction of survival or death following severe perinatal asphyxia and the development of hypoxic-ischemic encephalopathy. We hypothesized that low cerebral blood flow velocity, as determined by Doppler ultrasonography, may predict neurologic nonviability in a group of severely asphyxiated infants who exhibited signs of severe encephalopathy. Using the staging system of Sarnat and Sarnat, 11 infants who had had severe perinatal asphyxia were studied at the time that their neurologic examinations met the criteria for stage 3 encephalopathy. Apgar scores, cord or initial blood gases and pH, blood pressure, heart rate, and electroencephalographic findings were similar between those infants who survived (N = 8) and those who died due to cerebral injury (N = 3). Cerebral blood flow velocity, however, was significantly lower in those infants who died (3,288 +/- 884 vs 1,051 +/- 789 planimeter units/min; P less than .005). All infants who died had retrograde diastolic blood flow in the common carotid artery. In the study group the combination of low cerebral blood flow velocity and retrograde diastolic blood flow in the common carotid artery allowed prediction of survival and death with sensitivity and specificity of 100% (P less than .006). Following perinatal asphyxia and the development of severe encephalopathy, the finding of low cerebral blood flow velocity appears to be predictive of neurologic nonviability.