Prenatal diagnosis by amniocentesis and chorionic villus biopsy of mtDNA mutation 8993T > G.

The mtDNA mutation 8993T > G is associated with neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP) and Leigh syndrome. There are few reported cases of prenatal testing for mtDNA disorders. Specifically for 8993T > G, there are six cases in which prenatal diagnosis has been reported. We describe prenatal diagnosis in a 36-year-old G3P1 woman with 33% heteroplasmy in white blood cells. She had a previous child who died from Leigh disease (92% heteroplasmy). She underwent prenatal testing by both CVS and amniocentesis of the 8993T > G heteroplasmy levels. This is the first reported case in which both procedures were used. Heteroplasmy was similar in both tissues (58.6% CVS and 55% amniocentesis), in support of the theory that this testing is reliable and may be considered in prenatal cases where this mutation is known in the mother. To date, her child is 20 months old and developing normally. Heteroplasmy determination in the child was refused. Although the infant is developmentally normal, consistent with the observation that levels of heteroplasmy below 60% are compatible with a mild phenotype, this conclusion must be tempered by the limited period of observation and the fact that patients with the NARP phenotype often present later than 20 months of age.

A perimortem protocol for suspected genetic disease.

A considerable portion of pediatric deaths represent disease with risk of recurrence in subsequent family members. Procedures to obtain samples of body fluids and tissues suitable for diagnosis of mendelian and chromosomal disorders are described. These procedures, the "perimortem protocol," are used in studying children who died of suspected but undiagnosed genetic disease.

Apparent gastrointestinal origin of cis-4-hydroxycyclohexanecarboxylic acid.

We identified by gas chromatography-mass spectrometry the unusual substance cis-4-hydroxycyclohexanecarboxylic acid (4-HCH) in the urine of a child. Urinary excretion of 4-HCH and intestinal bacteria were both suppressed by neomycin treatment. We propose that 4-HCH is a by-product of bacterial metabolism.

Medication use during neonatal and pediatric critical care transport.

The Pediatric Critical Care Unit (PCCU) at the Children's Hospital of Western Ontario provides a transport service and team (critical care physician, critical care nurse, respiratory therapist) which transports critically ill newborns, infants, and children. The purpose of this study was to identify the medications used during transport and to determine age-related differences. Results of a prospective study of all drugs administered by the transport team to 174 patients during their stabilization and transport from November 1, 1987 through October 31, 1988 are presented. One hundred and twenty-one (69.5%) patients received at least one medication. The most frequently administered medications were antibiotics (38.5% of patients), followed by morphine (27.0%), anticonvulsants (23.6%), neuromuscular blockers (14.4%), respiratory drugs (11.5%), inotropes (10.9%), and sedatives (7.5%). Miscellaneous medications were administered to 48.8% of patients. The use of different classes of drugs varied with age; anticonvulsants were most frequently administered to children, sedatives and respiratory medications to infants, and antibiotics and miscellaneous medications to newborns. The wide range of medications used may reflect the diversity of diseases causing critical illness which reinforces that transport teams must have access to and knowledge of a variety of medications. The formulary of medications taken by the critical care transport team is included.

Teratogenic effects of ethyl alcohol administered to pregnant mice.

Concern has recently been renewed about detrimental effects of maternal alcoholism on human prenatal development. In light of current interest in maternal alcoholism, data are presented on the effects of ethyl alcohol administration to pregnant mice. Alcohol treatment consisted of intraperitoneal injection of 0.030 ml. per gram of body weight of a 25 per cent (v/v) solution of 95 per cent ethyl alcohol in saline. Following alcohol treatment on both of gestation days 8 and 9 or days 10 and 11 the frequency of fetal death was substantially elevated compared to saline-treated controls. Alcohol treatment on one of gestation days 7, 8, 9, 10, 11, or 12 resulted in significantly increased fetal death following alcohol treatment on day 8. The incidence of congenital anomalies was significantly increased following alcohol treatment only on gestation days 8, 9, or 10. The most frequently observed abnormalities were coloboma of the iris and ectrodactyly affecting the forepaws.

Role of transcutaneous pacing in the setting of a failing permanent pacemaker.

A 15-year-old boy with acute symptomatic bradycardia caused by a failing permanent pacemaker was paced transcutaneously in the emergency department. Failure to recognize that electrical interference from noncaptured permanent pacemaker beats precluded the usual demand mode of application of the transcutaneous pacemaker led to asystole. We present this case to point out the potential for asystole and ventricular dysrhythmia in this situation and to increase awareness of the role of the potentially lifesaving device in children.

Experimental hyperphenylalaninemia in the pregnant guinea pig: possible phenylalanine teratogenesis and p-chlorophenylalanine embryotoxicity.

Maternal hyperphenylalaninemia (HPH) due to deficient phenylalanine (Phe) hydroxylation is a recognized human teratogen associated with an increased incidence of intrauterine growth retardation, microcephaly, congenital heart disease, and mental retardation. There are no previous reports of experimental HPH during organogenesis. Sustained HPH was produced in pregnant guinea pigs by adding 3.5% Phe and 1.0% parachlorophenylalanine (pCPA), an inhibitor of Phe hydroxylase, to standard guinea pig chow. Animals consumed the supplemented test diets from gestation day 1 until killed on gestation day 17. Examination of day 17 embryos revealed that embryonic mortality was associated only with maternal pCPA administration and was independent of the degree of maternal HPH. Embryonic malformation was associated with maternal HPH as well as maternal pCPA administration. Both maternal HPH and pCPA administration were associated with embryonic growth retardation. There was no association between maternal food intake or plasma tyrosine levels and embryonic abnormality or mortality. Both Phe and tyrosine were found to be concentrated in gestation day 17 yolk sac fluid when compared to maternal plasma Phe and tyrosine. The association of embryonic malformation and maternal HPH is consistent with human data. The embryotoxicity of pCPA requires further study and highlights the necessity of appropriate controls in models of experimental HPH.

Acute respiratory failure mediated by reactive drug metabolites.

Reactive drug metabolites have been implicated in the pathogenesis of adverse reactions to the aromatic anticonvulsants. A patient presented with a hypersensitivity reaction to the aromatic anticonvulsants which evolved into Stevens-Johnson syndrome and was complicated by the presence of adult respiratory distress syndrome. When the patient's cells were tested for sensitivity in vitro to reactive metabolites of the aromatic anticonvulsants, they were markedly more sensitive to metabolites of the aromatic anticonvulsants than were the cells of controls (p < 0.05). The adult respiratory distress syndrome has not previously been described as a complication of hypersensitivity reactions to the aromatic anticonvulsants. In vitro testing also demonstrated cross-sensitivity to the anticonvulsants, allowing selection of a therapeutic regimen which would not be associated with a risk of exacerbating the hypersensitivity reaction.

Guidelines for stabilizing the condition of the critically ill child before transfer to a tertiary care facility.

The initial resuscitation and stabilization provided to a critically ill or injured child is often an important determinant of outcome. Before transfer to a tertiary care facility the initial care may be provided by physicians unaccustomed to managing critically ill children. The authors outline the unique aspects of resuscitation and stabilization of the critically ill child and give guidelines for the initial management of diseases affecting the central nervous system and respiratory tract (the most frequent indications for transfer to a tertiary care facility) and other, less frequent but important problems. In many situations it is worth while to enlist the expertise of the tertiary care centre, either by telephone consultation or by dispatch of a specially trained transport team.

Nephrocalcinosis and its relationship to treatment of hereditary rickets.

Renal ultrasonography was performed on 23 patients with X-linked hypophosphatemic rickets (XLH) and 11 patients with autosomal recessive vitamin D-dependent rickets (ARVDD). A pattern of increased echogenicity of the renal pyramids (ERP) was identified in 11/23 patients with XLH and 3/11 patients with ARVDD; this ultrasonographic finding has previously been associated with medullary nephrocalcinosis. Patients with XLH and ERP had significantly higher mean serum calcium and phosphate concentrations, more frequent episodes of hypercalcemia, and higher doses of oral vitamin D and phosphate during the first 3 years of therapy. Episodes of hypercalcemia were more frequent when patients received higher doses of vitamin D2 (greater than 4000 IU/kg/day) or 1,25-dihydroxycholecalciferol (greater than 40 ng/kg/day). Episodes of hypercalciuria were significantly increased at doses of greater than 20 ng/kg/day 1,25-dihydroxycholecalciferol. In patients with ARVDD, ERP was also correlated with vitamin D dose and frequency of hypercalcemia episodes. ERP was not associated with an elevation of serum creatinine or loss of urinary concentrating ability in either patient group.

The child requiring transport: lessons and implications for the pediatric emergency physician.

A retrospective review of the charts of all patients transported by our emergency transport team was done to determine the following characteristics: age, presenting problem, and outcome of patients and utilization of transport team personnel. Eighty-five percent of patients were under six years of age; central nervous system pathology accounted for 53% of patients transported, followed by respiratory problems (30%), cardiac problems (4.2%), and major trauma (2.7%). Sixty patients survived with normal neurologic examination at discharge. A statistically significant difference in retrospectively assigned PSI score (17.0 +/- 6.02 in nonsurvivors versus 5.8 +/- 6.02 in survivors) was observed. Utilization of the transport team was deemed appropriate. Comparison of our data with other available sources, as well as suggestions for emergency physicians and continuing medical education programs, is outlined.

Bilateral lower extremity compartment syndromes secondary to intraosseous fluid resuscitation.

Intraosseous infusions are reserved for use in life-threatening hypovolemic or cardiogenic shock when intravenous (i.v.) access cannot be readily established. Although minor fluid extravasation is a common problem with this technique, a fully established compartment syndrome has never been reported. We describe a child with severe compartment syndromes of both lower extremities complicating the use of intraosseous fluid resuscitation.

A portable nitric oxide scavenging system designed for use on neonatal transport.

OBJECTIVE: To evaluate a portable scavenging system for nitric oxide and its oxides, designed for use on neonatal transport. DESIGN: A prospective evaluation of the nitric oxide scavenging system, using a neonatal transport incubator ventilator and a test lung. SETTING: Laboratory of a tertiary care children's hospital. INTERVENTIONS: The scavenging system was tested, using a neonatal transport incubator with attached ventilator, ventilator circuit, and a neonatal test lung. Nitric oxide was administered on the inspiratory limb, and nitric oxide and its oxides were measured in the expiratory gas after passing through the scavenger. MEASUREMENTS AND MAIN RESULTS: A modified scrubber assembly was filled with 50% activated charcoal and 50% aluminas potassium permanganate pellets (3). Three wire meshes were placed before, in between, and after the two chemicals to facilitate gas flow. Using the maximum FIO2, with a nitric oxide concentration of 120 parts per million (ppm), the test lung continuous flow ventilation (FIO2 of 0.86, peak inspiratory pressure of 30 cm H2O, positive end-expiratory pressure of 6 cm H2O) and respiratory rate of 60 breaths/min) was performed for 4 hrs with each of four freshly prepared scavenging systems. A fifth scavenging system was tested for a 12-hr period. The mean composition of the exhaled gases for 4 hrs were: nitric oxide 0.01 +/- 0.03 (SD) ppm, nitric dioxide 0.06 +/- 0.06 ppm, and other oxides 0.05 +/- 0.09 ppm. After 12 hrs of 120 ppm of inhaled nitric oxide, the fifth scavenger system had undetectable nitric oxide, nitric dioxide, and other oxides in the exhaled gas. Normal room air contained between 0.0 and 0.03 ppm of nitric oxide, 0.0 and 0.02 ppm of nitric dioxide, and 0.0 and 0.02 ppm of other oxides. CONCLUSION: Nitric oxide, nitric dioxide, and other dioxides can be safely scavenged by this portable scavenging system, allowing safe administration of nitric oxide free from environmental contamination with nitric oxide and its oxides.

3-Methylglutaconic aciduria: a marker for as yet unspecified disorders and the relevance of prenatal diagnosis in a 'new' type ('type 4').

The Mendelian disorder known as 3-methylgutaconic aciduria (McKusick 250950) gives evidence of allelic and locus heterogeneity. Type 1 has a mild clinical phenotype and confirmed 3-methylgutaconyl-CoA hydratase deficiency; inheritance is autosomal recessive. Other forms have major clinical manifestations and subdivide into X-linked (type 2), a form in Iraqi Jews with optic atrophy (so-called type 3); and untyped (putative autosomal recessive) forms without identified enzyme defects. In the latter, 3-methylglutaconic aciduria may simply be a marker for another metabolic disorder. We describe a male proband with 3-methylglutaconic aciduria designated here as 'type 4' (autosomal recessive, with severe psychomotor phenotype and cerebellar dysgenesis). He is the offspring of Italian consanguineous parents. Born with congenital malformations, he has been followed for 18 years, showing profound developmental delay and cerebellar dysgenesis. Measures of hydratase activity in cultured fibroblasts from the proband and 11 additional patients (two with type 1 disease, 9 with either type 2 or an unspecified form) revealed deficient enzyme activity in type 1 cases and normal activity in the proband and the other 11 cases. Two of the untyped cases probably have 3-methylglutaconic aciduria of the type described here. Prenatal diagnosis in the form described here may be feasible by analysis of amniotic fluid metabolites in pregnancies at risk if the mother does not entirely remove elevated concentrations. A female sibling of the proband had normal metabolite values in amniotic fluid. Postnatal follow-up confirmed absence of the disease. We give the normal values for amniotic fluid and results on these additional fetuses at risk (none affected).

Jugular venous bulb catheterization in infants and children.

Cross-brain oxygen extraction may be altered by coma, hyperventilation, hypothermia, or barbiturates, and has been demonstrated in adults and more recently in children to be related to functional neurologic recovery after a variety of brain injuries. However, measurement of cross-brain oxygen extraction in children is currently not a part of routine clinical care, partly because there have been no published attempts relating the technique of jugular venous bulb (JVB) catheterization and its complication in children. We catheterized the JVB to measure cerebral venous oxygen content and calculate cross-brain oxygen extraction in 26 deeply comatose neonates and children ranging in age from a few hours to 14 yr. Bedside catheterization using the Seldinger technique was successful in 25 children, with standard venous cutdown necessary in the remaining child. All JVB catheterizations were performed with parental consent and during continuous monitoring of the intracranial (ICP) or fontanelle, as well as arterial, pressure. ICP was not significantly altered by the cannulation procedure in any of the children studied, although the cannulation occurred early in the child's course when ICP was well controlled. Inadvertent carotid artery puncture with bleeding controlled by local pressure occurred in four children, and catheter malposition was confirmed on lateral skull xray in two others. Jugular venous bulb catheters remained in place for 2 to 7 days (average 3) and malfunction or obstruction of the catheter did not occur. Organisms were grown from three of 26 catheter tips submitted for culture, with peripheral blood cultures also positive for the same organisms in two of these.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of referring physicians on interventions by a pediatric and neonatal critical care transport team.

The objective of this study was to determine the influence of: a) pediatrician versus nonpediatrician referrals on a transport team's therapeutic interventions and b) referring physician's year of graduation on interventions performed by the transport team. From November 1987 through December 1989 we prospectively compared the therapeutic interventions performed by the critical care transport team on newborns and pediatric patients with the referring physician's specialty and year of graduation. The transport team (critical care physician [PL3 or greater], registered respiratory therapist, critical care nurse), recorded all therapeutic interventions, including both procedural and pharmacologic, for 213 newborn and 149 consecutive pediatric transports. Referring physicians were categorized as pediatricians and nonpediatricians. Data were analyzed by analysis of variance, chi2, or linear regression. All patients were admitted to either the pediatric or the neonatal intensive care unit, and over 80% of both age groups received assisted ventilation. Newborns referred by nonpediatricians required significantly more procedural interventions (2.64 vs 1.91, P = 0.016) than those referred by pediatricians. The opposite relationship was observed among pediatric patients in that children referred by pediatricians received more frequent intervention (P = 0.008) than those referred by nonpediatricians. There was a significant inverse relationship between the referring physicians year of medical school graduation and the number of therapeutic interventions (total interventions = 6.17 - 0.040 x graduation year, P = 0.01) and procedural interventions (procedural interventions = 3.54 - 0.024 x graduation year, P = 0.01). We found that the referring physicians' medical training affected the number of interventions their patients received. Similarly, patients were likely to receive more interventions if the referral physicians training was not recent. These data have educational implications and support the concepts of continuing medical education, recertification, and maintenance of skills among physicians providing care to critically ill newborns and pediatric patients.

Pediatric and neonatal critical care transport: a comparison of therapeutic interventions.

OBJECTIVE: To compare the therapeutic interventions provided to newborn and pediatric patients by a dedicated combined neonatal pediatric critical care transport team. METHOD: From November 1987 through December 1989 we prospectively compared the number of therapeutic interventions performed by the critical care transport team on newborns and pediatric patients. The transport team (critical care physician [PL3 or greater], pediatric respiratory therapist, critical care nurse), recorded all therapeutic interventions, including both procedural and pharmacologic, for 213 newborn and 149 pediatric consecutive transports. Data were analyzed by analysis of variance or chi 2 statistic. RESULTS: All patients were admitted to either the pediatric or the neonatal intensive care unit, and over 80% of both age groups received assisted ventilation. Newborns commonly suffered from respiratory diseases (159/213), while pediatric patients suffered from respiratory (52/149), central nervous system (28/149), and traumatic conditions (37/149). Airway maintenance procedural interventions (intubation, ventilation) were the commonest in both groups, although more frequent in neonates. Neonates received antibiotics and morphine (P < 0.05) while pediatric patients received anticonvulsants and respiratory drugs (P < 0.05) more frequently. Newborns received significantly more interventions than pediatric patients (average 3.56 vs 2.93, P < 0.05). Newborns also received significantly more procedural interventions (2.06 vs 1.36, P = < 0.05) including intubation (34.7% vs 15.4%, P < 0.05) and the initiation of mechanical ventilation (38% vs 22%, P < 0.05). CONCLUSION: Overall, newborns received more interventions, including intubation, and ventilation from the transport team than did pediatric patients. Our data suggest that combined pediatric neonatal transport teams should be prepared to intervene in a wide range of conditions from preterm respiratory distress to the multiply traumatized adolescent.