Classification of perinatal deaths: development of the Australian and New Zealand classifications.

Classifications of perinatal deaths have been undertaken for surveillance of causes of death, but also for auditing individual deaths to identify suboptimal care at any level, so that preventive strategies may be implemented. This paper describes the history and development of the paired obstetric and neonatal Perinatal Society of Australia and New Zealand (PSANZ) classifications in the context of other classifications. The PSANZ Perinatal Death Classification is based on obstetric antecedent factors that initiated the sequence of events leading to the death, and was developed largely from the Aberdeen and Whitfield classifications. The PSANZ Neonatal Death Classification is based on fetal and neonatal factors associated with the death. The classifications, accessible on the PSANZ website (http://www.psanz.org), have definitions and guidelines for use, a high level of agreement between classifiers, and are now being used in nearly all Australian states and New Zealand.

Correlates of prepubertal bone mineral density in cystic fibrosis.

AIM: To examine early factors in bone mineral accretion in cystic fibrosis (CF). METHODS: In 22 prepubertal children with CF and mild lung disease, the relation between total body bone mineral density (BMD) and measures of body composition, biochemistry, lung function, and physical activity was studied. RESULTS: There was a non-significant mild reduction in mean total body BMD. No relation was found between BMD and anthropometric indices, fat free soft tissue, degree of lung disease, degree of fat malabsorption, dietary energy intake, or level of physical activity. Significant impairments in physical growth were apparent in this population and were found to correlate with degree of lung disease. CONCLUSION: A CF specific factor appears unlikely to be associated with the osteopenia commonly found in CF. Careful attention to general aspects of lifestyle and nutrition is recommended to maximise bone mineral accretion in this population.

Piracetam therapy does not enhance cognitive functioning in children with down syndrome.

BACKGROUND: Piracetam is widely used as a purported means of improving cognitive function in children with Down syndrome. Its efficacy, however, has not been rigorously assessed. OBJECTIVE: To determine whether 4 months of piracetam therapy (80-100 mg/kg per day) enhances cognitive function in children with Down syndrome. DESIGN: A randomized, double-blind, placebo-controlled crossover study. PARTICIPANTS AND METHODS: Twenty-five children with Down syndrome (aged 6.5-13 years) and their caregivers participated. After undergoing a baseline cognitive assessment, children were randomly assigned to 1 of 2 treatment groups: piracetam-placebo or placebo-piracetam. MAIN OUTCOME MEASURE: The difference in performance while taking piracetam vs while taking placebo on tests assessing a wide range of cognitive functions, including attention, learning, and memory. RESULTS: Eighteen children completed the study, 4 withdrew, and 3 were excluded at baseline. Piracetam therapy did not significantly improve cognitive performance over placebo use but was associated with central nervous system stimulatory effects in 7 children: aggressiveness (n = 4), agitation or irritability (n = 2), sexual arousal (n = 2), poor sleep (n = 1), and decreased appetite (n = 1). CONCLUSION: Piracetam therapy did not enhance cognition or behavior but was associated with adverse effects.

HEDJ, an Hsp40 co-chaperone localized to the endoplasmic reticulum of human cells.

Hsp40 co-chaperones, characterized by the presence of a highly conserved J domain, are involved in nearly all aspects of protein synthesis, folding, and secretion. Within the lumen of the endoplasmic reticulum, these chaperones are also involved in reverse translocation and degradation of misfolded proteins. We describe here the cloning and characterization of a novel Hsp40 chaperone, which we named HEDJ. Epitope-tagged HEDJ was demonstrated by confocal microscopy to be localized to the endoplasmic reticulum. Protease susceptibility, glycosidase treatment, and detergent solubility assays demonstrated that the molecule was luminally oriented and membrane-associated. In vitro experiments demonstrated that the J domain interacted with the endoplasmic reticulum-associated Hsp70, Bip, in an ATP-dependent manner and was capable of stimulating its ATPase activity. HEDJ mRNA expression was detected in all human tissues examined. Highly homologous sequences were found in mouse, Drosophila, and Caenorhabditis elegans data bases. These results suggest potential roles for HEDJ in protein import, folding, or translocation within the endoplasmic reticulum.

Comparison of total body chlorine, potassium, and water measurements in children with cystic fibrosis.

BACKGROUND: Symptoms of cystic fibrosis (CF) may limit the utility of total body chlorine (TBCl) and total body potassium (TBK) measurements for assessing body fluid compartments of children. OBJECTIVE: This study assessed relations among independent measurements of TBCl, TBK, and total body water (TBW) in children with CF. DESIGN: We compared cross-sectional measurements of TBCl by in vivo neutron activation analysis, TBK by whole-body counting of (40)K, TBW by D(2)O dilution [TBW(D(2)O)], and TBW from TBCl and TBK [TBW(Cl + K)] in 19 prepubertal children (13 boys) aged 7.6-12.5 y who had mild symptoms of CF. Body-composition measurements were compared with data from previous studies of healthy children. RESULTS: Subjects with CF had deficits in TBCl, TBK, TBW, and body weight compared with control reference data (P < 0.05). The ratios (TBCl + TBK)/TBW and TBCl/TBK were not significantly different from control reference values, and plasma chlorine and potassium concentrations were within control reference ranges. The sum of TBCl and TBK correlated with TBW(D(2)O) (r(2) = 0.79, P < 0.001), and TBW(Cl + K) correlated with TBW(D(2)O) (r(2) = 0.78, P < 0.001). TBW(Cl + K) was similar to TBW(D(2)O) (mean +/- SEM: 19.0 +/- 0.5 compared with 19.4 +/- 0.5 L; NS). CONCLUSIONS: Prepubertal children with mild symptoms of CF can develop deficits in TBCl, TBK, and TBW that reflect chronic energy malnutrition. Mild symptoms of CF do not appear to affect normal relations among TBCl, TBK, and TBW. Measurements of TBCl and TBK may be used to assess body fluid compartments in these patients.

Short-chain acyl-CoA dehydrogenase deficiency: a cause of ophthalmoplegia and multicore myopathy.

OBJECTIVE: To determine an underlying genetic defect within the differential diagnosis of congenital multicore myopathy. BACKGROUND: A 13.5-year-old girl presented with congenital-onset facial and neck weakness, slowly progressive severe limb girdle and axial myopathy, respiratory weakness, cardiomyopathy, progressive joint contractures, lumbar lordosis, progressive external ophthalmoplegia with ptosis, and cataracts. Muscle biopsy at 3 years revealed type I fiber predominance and hypotrophy, multicores with a focal decrease in mitochondria and oxidative enzymes, and internal nuclei. METHODS AND RESULTS: Serum carnitine was decreased (total, 18.2 micromol/L; free, 11.7 micromol/L). Urine organic acids intermittently revealed very large amounts of ethylmalonic and methylsuccinic acids intermittently, with elevated butyrylglycine, 2-methylbutyrylglycine, and tiglylglycine. Fibroblast acylcarnitine profiles revealed marked butyrylcarnitine elevation. Electron-transferring flavoprotein-linked reduction enzymatic assay of fibroblasts with butyryl-coenzyme A (CoA) as substrate, after immunoinactivation of medium-chain acyl-CoA dehydrogenase activity, revealed a complete absence of short-chain acyl-CoA dehydrogenase (SCAD) activity. No SCAD protein was detectable with Western blot analysis. CONCLUSIONS: This patient expands the clinical phenotype of SCAD deficiency and emphasizes the need for its consideration in the differential diagnosis of progressive external ophthalmoplegia and congenital multicore myopathy.

Tumor cell apoptosis present at diagnosis may predict treatment outcome for patients with medulloblastoma.

PURPOSE: To determine if the degree of tumor cell apoptosis at diagnosis predicts outcome, tissue sections of medulloblastoma were examined and the amount of apoptosis and progression-free survival were correlated. PATIENTS AND METHODS: The study cohort consisted of 43 children in whom medulloblastoma was diagnosed between 1984 and 1995: 29 patients at high risk (HR) treated with radiation and chemotherapy, and 14 children at low risk (LR) treated with radiation alone. A terminal deoxynucleotidyl transferase (TdT) end-labeling assay was used to detect apoptosis in paraffin-embedded tissue sections prepared at diagnosis. RESULTS: Progression-free survival was examined in cohorts of children whose tumors were divided into quartiles based on the apoptotic index (AI) of their pretreatment tumor specimens. A comparison of these four groups of children revealed an association between AI and outcome (p = 0.03); patients with tumors in the highest AI quartile had substantially improved outcome compared to all other patients combined (p = 0.02). In this cohort of patients treated with different therapies, assignment at the time of diagnosis to LR and HR groups based on widely-accepted clinical criteria was not closely associated with outcome (p = 0.47). CONCLUSION: AI is a strong indicator of treatment outcome for children with medulloblastoma after treatment with cytotoxic therapy, independent of risk group. Because HR and LR patients included in this study received different modalities of cytotoxic therapy, it is possible that AI predicts outcome independent of the precise antineoplastic therapy a patient receives.

[Benign paroxysmal torticollis. Recurrent involuntary twisting of the head in infants and young children]. / Benign paroksystisk torticollis. Recidiverende tvangsholdning af hovedet hos spoed- og småbørn.

Benign paroxysmal torticollis occurs in infancy and early childhood. The etiology is unknown, although a vasomotor labyrinthine pathophysiology is possible. We report four cases with onset at ages of two to six months of recurrent episodes of torticollis and discomfort persisting between three hours and seven days. In three cases the torticollis was alternating. Photography or videorecording made by the parents during the attacks were helpful for the diagnosis in three cases. MRI may in some cases be necessary to rule out a space occupying lesion in the posterior fossa.

Recurrent seizures in metachromatic leukodystrophy.

The unusual presentation of juvenile onset metachromatic leukodystrophy (MLD) and frequent complex partial seizures in a patient led us to perform a retrospective study of 18 patients with MLD to identify the prevalence and type of recurrent seizures during the first 2 years of the disease. Five of 17 patients (29%) had developed recurrent seizures within 12 months of the onset of symptoms, and one patient was lost to follow-up. By 24 months after onset of symptoms, 5 patients were lost to follow-up, and 6 of the remaining 13 patients (46%) had developed recurrent seizures. In all, 7 patients, 4 with late infantile-onset and 3 with juvenile-onset disease, developed recurrent seizures. Four patients, including 3 with juvenile-onset disease had complex partial seizures. We conclude that recurrent seizures are common in MLD and may occur at any stage of the disease, particularly in patients with juvenile onset. Generalized seizures are more frequent in patients with late infantile-onset, whereas partial seizures are more common in those with juvenile-onset disease.

Molecular analysis redefines three human chromosome 14 deletions.

We have used a panel of 13 DNA markers in the distal region of chromosome 14q to characterize deletions in three patients determined cytogenetically to have a ring or terminally deleted chromosome 14. We have characterized one patient with a ring chromosome 14 [r (14) (p13q32.33)] and two with terminal deletions [del (14) (pter-->q32.3:)]. The two patients with cytogenetically identical terminal deletions of chromosome 14 were found to differ markedly when characterized with molecular markers. In one patient, none of the markers tested were deleted, indicating that the apparent terminal deletion is actually due to either an undetected interstitial deletion or a cryptic translocation event. In the other patient, the deletion was consistent with the cytogenetic observations. The deleted chromosome was shown to be of paternal origin. The long-arm breakpoint of the ring chromosome was mapped to within a 350-kb region of the immunoglobulin heavy chain gene cluster (IGH). This breakpoint was used to localize markers D14S20 and D14S23, previously thought to lie distal to IGH, to a more proximal location. The ring chromosome represents the smallest region of distal monosomy 14q yet reported.

Pediatric medication errors: predicting and preventing tenfold disasters.

Tenfold errors in pediatric doses are not uncommon. Because the needed volume of stock solution is generally small, even a tenfold higher volume may still appear deceivingly normal. Such errors are much less likely to occur in adults, because it would result in unacceptably large volumes of stock solution. Other sources of tenfold errors are communication difficulties with parents and illegible writing of orders by physicians. Testing health professionals may identify subgroups of individuals who are prone to commit such errors. Independent double checking of calculations and a mechanism to resolve disagreement is being practiced in most academic institutions. Transition to patient's unit dose is likely to decrease calculation errors, because pharmacists commit fewer errors. Hazardous drugs that are not required on a stat basis should be removed from the wards.

Neuronal intranuclear hyaline inclusion disease with progressive cerebellar ataxia.

Neuronal intranuclear hyaline inclusion disease is a progressive, fatal neurologic condition characterized by eosinophilic inclusions in neurons of the central, autonomic, and peripheral nervous systems. The clinical and pathologic findings of a 4-year-old boy who presented with a rapidly progressive cerebellar ataxia and seizure disorder that had begun 2 years earlier are described. Although intraneuronal inclusions were identified in neurons of cortex, basal ganglia, brainstem, cerebellum, and spinal cord, clinical signs were restricted to cerebellar ataxia, internuclear ophthalmoplegia, and cognitive delay. Predominant cerebellar atrophy, early age of onset, and short clinical course distinguishes it from previously reported patients.