Evaluation of selection criteria for validating paired umbilical cord blood gas samples: an observational study.

OBJECTIVE: To compare six validation criteria for umbilical cord blood gas (UCBG) values in vigorous and nonvigorous neonates. DESIGN: Retrospective cohort study. SETTING: Single tertiary obstetric centre, King Edward Memorial Hospital (KEMH), Perth, Western Australia. SAMPLE: A total of 37,763 consecutive deliveries at >23 weeks of gestation. METHODS: Six validation criteria were compared to evaluate the proportion of deliveries with 'valid' UCBG data; and the proportion of vigorous and nonvigorous neonates with metabolic acidaemia. MAIN OUTCOMES: Proportion of deliveries with 'valid' UCBG values; proportions of vigorous and nonvigorous neonates with normal, borderline and abnormal UCBG values. RESULTS: The criteria based on KEMH 5th centile arteriovenous pH and Pco(2) differences resulted in a higher proportion of neonates with 'valid' UCBG values than the previously described Westgate and Kro criteria. The increase in 'valid' UCBG values occurred across the entire study population including vigorous and nonvigorous neonates. Among neonates with short-term neonatal complications there was an increase in nonvigorous neonates with umbilical artery metabolic acidaemia. There was no corresponding increase in vigorous neonates diagnosed with abnormal UCBG values. CONCLUSIONS: Use of the KEMH criteria results in an increase in the proportion of nonvigorous term neonates with UCBG data considered 'valid' to aid clinicians in the management of the neonate shortly after delivery. This change occurs without increasing the rate of false-positive diagnoses of acidaemia in vigorous neonates. The KEMH 'validation' criteria were developed from an entire presenting population and provide a simple algorithm that can be universally applied to identify neonates with nonphysiological UCBG values.

Outcomes of neonatal chylous effusions: A 20-year west-Australian tertiary center experience.

Neonatal chylous effusions are rare entity with limited evidence-based management. We conducted a retrospective review of neonates admitted to King Edward Memorial and Princess Margaret/Perth Children's Hospital over 20 years with laboratory-confirmed chylous effusions. A total of 51 infants with chylous effusion were identified. Median gestational age and birth weight were 35.5 weeks and 2620 grams respectively. Congenital [27/ 51] and acquired [24/51] cases were included. Antenatal interventions were performed in 17/22 with antenatal hydrops and 50/51 needed postnatal drains. Effusions were monitored with serial (≥2) chest ultrasounds in 29/51 infants and multiple (≥5) x-rays in 45/51 infants. Median duration of mechanical ventilation, oxygen requirement, and hospital stay was 294.5 hours, 400 hours, and 49 days respectively. 39/51 received medium chain triglyceride (MCT) diet while 8/51 received octreotide. Six infants died during hospital stay. 12/19 had normal developmental assessment at one-year. The acquired group had higher number of xrays done, need for MCT diet and inotropes, and hospital stay vs congenital group. Duration of drains, radiological investigations and immunoglobulin administration were higher in neonates who received octreotide. Syndromic association, duration of ventilation and oxygenation were risk factors for mortality. In our setting, neonatal chylous effusions are associated with significant morbidity and mortality.

Outreach obstetrics training in Western Australia improves neonatal outcome and decreases caesarean sections.

The objective of this study was to determine the effect of a multi-professional outreach obstetric training programme on perinatal and neonatal outcomes. This was a retrospective comparison of 5-min low Apgar scores, stillbirth, perinatal death and moderate/severe hypoxic ischaemic encephalopathy rates in 127,753 infants born in Western Australia before and after the introduction of training in rural and remote areas. Following the introduction of the training programme, there was a highly significant (p = 0.003) decrease in the rate of infants born with low 5-min Apgar scores (from 20.4 to 15.4/1,000 live births). While the changes in the other three outcomes were not significant, all three demonstrated a trend for improvement in the intervention area. This is the second study of an educational intervention in obstetrics to demonstrate improvement in neonatal outcome and the first to be associated with a decrease in caesarean sections.

An integrated strategy for the diagnosis of neuronal ceroid lipofuscinosis types 1 (CLN1) and 2 (CLN2) in eleven Latin American patients.

The neuronal ceroid lipofuscinoses (NCLs) are a family of progressive neurodegenerative diseases that are characterized by the cellular accumulation of ceroid lipofuscin-like bodies. NCL type 1 (CLN1) and type 2 (CLN2) are caused by deficiencies of the lysosomal enzymes palmitoyl-protein thioesterase 1 (PPT-1) and tripeptidyl peptidase 1 (TPP-1), respectively. In this study, 118 Latin American patients were examined for NCL using an integrated multidisciplinary program. This revealed two patients affected by CLN1 and nine by CLN2. Both CLN1 patients had a juvenile-onset phenotype with mutation studies of one patient demonstrating the known mutation p.Arg151X and a novel mutation in intron 3, c.363-3T>G. Six of the CLN2 patients presented with the 'classical' late-infantile phenotype. The remaining three patients, who were siblings, presented with a 'protracted' phenotype and had a higher level of residual TPP-1 activity than the 'classical' CLN2 patients. Genotype analysis of the TPP1 gene in the 'classical' CLN2 patients showed the presence of the known mutation p.Arg208X and the novel mutations p.Leu104X, p.Asp276Val, and p.Ala453Val. The siblings with the 'protracted' phenotype were heterozygous for two known TPP1 mutations, p.Gln66X and c.887-10A>G. This multidisciplinary program is also being used to diagnose other NCL types.

Congenital CLN8 disease of neuronal ceroid lipofuscinosis: a novel phenotype. / Enfermedad CLN8 congenita de lipofuscinosis neuronal ceroidea: un nuevo fenotipo.

INTRODUCTION: CLN8 disease is one of the thirteen recognized genetic types of neuronal ceroid lipofuscinosis, a group of neurodegenerative lysosomal storage disorders, most frequent in childhood. A putative 286 amino acids transmembrane CLN8 protein with unknown function is affected. Pathological variants in the CLN8 gene were associated with two different phenotypes: variant late-infantile in individuals from many countries worldwide, and epilepsy progressive with mental retardation, appearing in Finnish and Turkish subjects. CASE REPORT: The girl showed psychomotor delay and dementia since birth, tonic-clonic seizures, myoclonus, ataxia with cerebellar atrophy, and early death at 12 years old. Electron microscopy of the skin showed mixed GROD, curvilinear, fingerprint cytosomes and mitochondrial hypertrophy. Two pathological DNA variants in the CLN8 gene (exon 2 c.1A>G; p.?/ exon 3 c.792C>G; p.Asn264Lys) were found confirming a compound heterozygous genotype. CONCLUSION: This case is the Latin American index for a new congenital phenotype of the CLN8 disease. The congenital phenotype has to be added to the clinical spectrum of the CLN8 disease. The suspicion of CLN8 disease should be genetically sustained in challenging cases of a neurodegenerative syndrome with psychomotor delay since birth, speech difficulty and seizures. The course includes ataxia, cerebellar atrophy, and early death.

TITLE: Enfermedad CLN8 congenita de lipofuscinosis neuronal ceroidea: un nuevo fenotipo.Introduccion. La enfermedad CLN8 es uno de los 13 tipos geneticos reconocidos de lipofuscinosis neuronal ceroidea, un grupo de trastornos neurodegenerativos de acumulacion lisosomica, los mas frecuentes en la infancia. La causan mutaciones en la proteina transmembrana CLN8 de 286 aminoacidos, cuya funcion se desconoce. Las variantes patologicas en el gen CLN8 se asociaron con dos fenotipos diferentes: la variante infantil tardia en individuos de diversos paises alrededor del mundo, y la epilepsia progresiva con retraso mental, que aparece en pacientes finlandeses y turcos. Caso clinico. Niña que mostro retraso psicomotor y demencia desde el nacimiento, convulsiones tonicoclonicas, mioclonia, ataxia con atrofia cerebelosa y muerte temprana a los 12 años. La microscopia electronica de la piel mostro una mezcla de citosomas con patrones de depositos osmiofilicos granulares, curvilineos y de «huella digital¼, y mitocondrias hipertrofiadas. Se encontraron dos variantes patologicas de ADN en el gen CLN8 (exon 2 c.1A>G; p.?/ exon 3 c.792C>G; p.Asn264Lys), lo que confirmo un genotipo heterocigoto compuesto. Conclusion. Este es el caso indice en America Latina para el nuevo fenotipo congenito de la enfermedad CLN8. La sospecha de esta patologia deberia sustentarse geneticamente en casos de sindrome neurodegenerativo con retraso psicomotor desde el nacimiento, dificultad del habla y convulsiones. El curso clinico incluye ataxia, atrofia cerebelosa y muerte temprana.

An update of the results of intensive therapy in children with acute lymphoblastic leukemia.

On January 1984 a protocol for newly diagnosed children with acute lymphoblastic leukemia started in a multiinstitutional setting in Argentina, Costa Rica and Cuba. The protocol was based on the BFM 76/79 study. It consisted in 8 drug 8 weeks induction-consolidation regimen with a delayed intensification regimen followed by maintenance with 6-mercaptopurine-methotrexate and pulses with vincristine-prednisone for 36 months. CNS prophylaxis with IT therapy, age based schedule was given. Only patients with greater than 50000 WBC counts received cranial irradiation. A total of 720 patients were registered up to June 1987, 703 of them were eligible. Six hundred an twenty six (89%) of the patients achieved complete remission, 7 partial remission, 8 failed to respond and 62 (9%) had drug or disease related death before completing induction therapy. At 72 months 50% remained in complete remission, 45% and 58% of all the patients remained disease-free and alive respectively. Sites of relapse were bone marrow 21%, CNS 10%, testis 2%, combined 4% and 8% died in complete remission. No difference in response was observed among the three prognostic groups, however the disease-free survival at 72 months was 52% for good prognosis compared to 42% for intermediate and poor prognosis (P = 0.0009). This results showed a marked improvement over previous studies of our group and, that, intensive and large clinical trials can be performed in Latinamerica.

Arterial hypotension and prerenal failure in an extremely preterm infant associated with oral sildenafil.

We report significant hypotension and prerenal failure in an extremely preterm infant following two doses of oral sildenafil that warranted discontinuation of the drug and treatment with inotropes. Blood pressure and urine output normalized after 24 h of withdrawal of the oral drug. Sildenafil should be used cautiously in extremely preterm infants early in the neonatal course, where there is limited data on its efficacy and safety.

Effect of interval from fetal corticosteriod treatment to delivery on postnatal lung function of preterm lambs.

The effect of altering the interval from treatment to delivery on postnatal lung function of the preterm lamb is unknown. We treated groups of 8-10 singleton fetal sheep with 0.5 mg/kg betamethasone by fetal injection and evaluated postnatal lung function 40 min after preterm delivery at 123 days gestation 2 days after treatment or at 128 days gestation 2, 4, and 7 days after treatment relative to groups of 4-8 saline-injected control animals. At 123 days, betamethasone significantly improved arterial PCO2, dynamic thoracic compliance, and ventilatory efficiency index and doubled lung gas volume relative to a control group. Fetal treatment with betamethasone 2, 4, or 7 days before delivery at 128 days also improved these same indicators of lung function relative to controls, and the magnitude of the improvements was the same for all indicators and independent of treatment-to-delivery interval. Betamethasone suppressed the normal postnatal increase in plasma cortisol after 2 and 4 days of exposure but not after 7 days of exposure. Betamethasone also increased fetal and postnatal triiodothyronine concentrations after 2 days of exposure but not at 4 or 7 days of exposure. Although the hormone effects were transient, postnatal lung functional responses to betamethasone persisted over the 2- to 7-day interval from treatment to delivery.

Intraperitoneal phosphate administration in hungry bone syndrome.

Hypophosphatemia complicating parathyroidectomy for secondary hyperparathyroidism in renal failure is usually corrected by the oral or intravenous routes. We present a case in which those methods of treatment were not possible, and the phosphate was administered intraperitoneally. Phosphate was added as one molar sodium diphosphate solution to the dialysis fluid. In our case the procedure was well tolerated, phosphate blood levels were rapidly corrected, no alterations in calcium, magnesium or other parameters were detected and the patient was discharged in good condition. In selected cases of hungry bone syndrome after parathyroidectomy, intraperitoneal phosphate can be used safely.

Non oliguric acute renal failure after treatment with sulfinpyrazone.

Two cases with acute reversible renal failure while receiving sulfinpyrazone after acute myocardial infarction are presented. Sulfinpyrazone 200 mg q.i.d. was started a few days after the myocardial infarction. In both patients BUN and creatinine rose significantly, and returned to previous values when the drug was discontinued. No other known causes of renal failure were present in either of the patients.

Therapeutic approaches to the challenge of neuronal ceroid lipofuscinoses.

The Neuronal Ceroid Lipofuscinoses (NCLs) are lysosomal storage diseases (LSDs) affecting the central nervous system (CNS), with generally recessive inheritance. They are characterized by pathological lipofuscin-like material accumulating in cells. The clinical phenotypes at all onset ages show progressive loss of vision, decreasing cognitive and motor skills, epileptic seizures and premature death, with dementia without visual loss prominent in the rarer adult forms. Eight causal genes, CLN10/CTSD, CLN1/PPT1, CLN2/TPP1, CLN3, CLN5, CLN6, CLN7/MFSD8, CLN8, with more than 265 mutations and 38 polymorphisms (http://www.ucl.ac.uk/ncl) have been described. Other NCL genes are hypothesized, including CLN4 and CLN9; CLCN6, CLCN7 and possibly SGSH are under study. Some therapeutic strategies applied to other LSDs with significant systemic involvement would not be effective in NCLs due to the necessity of passing the blood brain barrier to prevent the neurodegeneration, repair or restore the CNS functionality. There are therapies for the NCLs currently at preclinical stages and under phase 1 trials to establish safety in affected children. These approaches involve enzyme replacement, gene therapy, neural stem cell replacement, immune therapy and other pharmacological approaches. In the next decade, progress in the understanding of the natural history and the biochemical and molecular cascade of events relevant to the pathogenesis of these diseases in humans and animal models will be required to achieve significant therapeutic advances.

Externally applied abdominal vibration as a method for improving efficiency of peritoneal dialysis.

We studied the effect of externally applied vibration onto the abdominal wall on the efficiency of peritoneal dialysis (PD). Ten patients were studied. Three consecutive PD exchanges (control sessions, CS) were compared with vibration sessions (VS). Samples of blood and dialysate were analyzed for urea nitrogen (UN), creatinine (Cr) and potassium (K). Mean clearance was calculated. We found that vibration increased significantly the mean UN, Cr and K clearances.

C-reactive protein as a diagnostic tool of sepsis in very immature babies.

Three hundred and nine septic screens were performed on 123 consecutively admitted infants of < 30 weeks gestation. As part of the septic screen, serial quantitative measurements of C-reactive protein (CRP) were performed daily until discontinuation of antibiotic therapy. Complete blood counts were performed daily for the first 2 days of each septic episode. The babies had a mean birth weight of 1035.8 g s.d. 273.2 and a mean gestational age of 27 weeks s.d. 1.8. A CRP level of 10 mg/L or above was considered abnormal. Subsequently the receiver operator characteristic curve for CRP was constructed to demonstrate the ideal cut off value. Of the 309 septic screens, there were 51 instances of proven sepsis and 39 instances of deep culture negative sepsis. In the remaining 219, a diagnosis of proven or deep culture negative sepsis could not be made. On the first day of the septic episode CRP showed a sensitivity of 62.7%, specificity of 87.2% and negative predictive value of 92.2% for proven sepsis. There was a significant increase in the sensitivity (90.2%) and negative predictive value (97.7%) of CRP with a specificity of 80.6 when both day 1 and 2 estimations were combined. We conclude that when the CRP is elevated on day 1 and/or day 2, the diagnosis of sepsis is extremely likely and when the CRP is within normal limits on days 1 and 2 of the septic episode, neonatal sepsis can be confidently excluded and antibiotic therapy ceased.

Morphine increases synchronous ventilation in preterm infants.

OBJECTIVE: To examine the short-term cardiorespiratory effects of intravenous morphine infusion in ventilated preterm infants. METHODOLOGY: A randomized double-blind placebo-controlled trial in a neonatal intensive care unit. Twenty-six preterm infants (29-36 weeks gestation) with hyaline membrane disease requiring ventilatory assistance on the first day after birth were included in the study. A loading dose of morphine 100 micrograms/kg over 30 min followed by a continuous intravenous infusion at 10 micrograms/kg per hour was given. Primary measures were heart rate, blood pressure, respiratory rate and interaction of spontaneous respiration with mechanical ventilation. Secondary measures were durations of oxygen therapy, ventilator therapy and hospitalization as well as incidence of bronchopulmonary dysplasia, periventricular haemorrhage and pneumothorax. RESULTS: Morphine-treated infants spent a significantly greater percentage of total ventilated time breathing in synchrony with their ventilators (median [IQ] = 72[58-87] vs 31[17-51]%; P = 0.0008). Heart rate and respiratory rate, but not blood pressure, were reduced in morphine-treated infants. Duration of oxygen therapy was reduced (median [IQ] = 4.5[3-7] vs 8[4.75-12.5] days; P = 0.046). CONCLUSIONS: Intravenous morphine infusion increases synchronicity of spontaneous and ventilator-delivered breaths in preterm infants. Morphine reduces heart rate and respiratory rate without reducing blood pressure, and may help to reduce duration of oxygen therapy in preterm infants with hyaline membrane disease.