Showing papers by "Montreal Children's Hospital published in 1995"

A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase

Abstract: Hyperhomocysteinaemia has been identified as a risk factor for cerebrovascular, peripheral vascular and coronary heart disease. Elevated levels of plasma homocysteine can result from genetic or nutrient-related disturbances in the trans-sulphuration or re-methylation pathways for homocysteine metabolism. 5, 10-Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the predominant circulatory form of folate and carbon donor for the re-methylation of homocysteine to methionine. Reduced MTHFR activity with a thermolabile enzyme has been reported in patients with coronary and peripheral artery disease. We have identified a common mutation in MTHFR which alters a highly-conserved amino acid; the substitution occurs at a frequency of approximately 38% of unselected chromosomes. The mutation in the heterozygous or homozygous state correlates with reduced enzyme activity and increased thermolability in lymphocyte extracts; in vitro expression of a mutagenized cDNA containing the mutation confirms its effect on thermolability of MTHFR. Finally, individuals homozygous for the mutation have significantly elevated plasma homocysteine levels. This mutation in MTHFR may represent an important genetic risk factor in vascular disease.

Differential response to pain by very premature neonates.

Abstract: The ability of very low birth weight (VLBW) premature infants to respond differentially to real versus a sham heelstick conditions was examined in this crossover study. Using a multidimensional assessment of responses of premature infants (n = 48) between 26 and 31 weeks gestational age (GA) at the time of the study, it was found that they respond differentially to real versus sham heelstick both behaviourally and physiologically. The multivariate effect of condition (real/sham) was significant with maximum heart rate and upper facial action (lower facial action was not scored) contributing significantly to the main effect. GA had a main multivariate effect, with the younger infants responding less robustly. The variability outcome measures of heart rate standard deviation and range of transfontanelle intracranial pressure contributed significantly to the main effect of GA, but not to the effect of condition. Young VLBW premature infants are capable of a multidimensional differential response to pain. GA is an important factor to consider when assessing pain in premature infants.

"I hardly cried when I got my shot!" Influencing children's reports about a visit to their pediatrician.

Abstract: We examined, in 2 phases, the influence of postevent suggestions on children's reports of their visits to a pediatrician. Phase 1 examined the effect of giving one of 3 types of feedback to 5-year-old children immediately following their Diphtheria Pertussis Tetanus (DPT) inoculation. Children were given pain-affirming feedback (the shot hurt), pain-denying feedback (the shot did not hurt), or neutral feedback (the shot is over). 1 week later, they did not differ in their reports concerning how much the shot hurt or how much they cried. In Phase 2, the same children were visited approximately 1 year after their inoculation. During 3 separate visits, they were either given additional pain-denying or neutral feedback. They were also given misleading or nonmisleading information about the actions of the pediatrician and the assistant. Children given pain-denying feedback reported that they cried less and that the shot hurt less than did children given neutral feedback. Those who were given misleading information about the actions of the assistant and the pediatrician made more false allegations about their actions than did children who were not given this information. These results challenge the view that suggestibility effects are confined to peripheral, nonaction events; in this study children's reports about salient actions involving their own bodies in stressful conditions were influenced.

The Determination of Sensory Deficits in Children With Hemiplegic Cerebral Palsy

Abstract: Therapeutic intervention for children with cerebral palsy begins with accurate appraisal of abilities and disabilities. Currently, treatment focuses on the identified motor deficits, with any underlying sensory deficits often being overlooked. Sensory input is an essential component of motor function and motor control. Therefore, the objective of this study was to determine the presence and extent of sensory deficits in school-aged hemiplegic children using a formal clinical sensory battery, as well as somatosensory evoked potentials. A cross-sectional comparative study was performed comparing sensory function in hemiplegic children and healthy controls. Nine hemiplegic children and 41 healthy controls between 4 and 19 years of age were assessed. Hemiplegic children were included if they had a minimum level of receptive language function of 30 to 33 months and expressive language ability of 24 to 27 months, and no severe limitation of joint range of the hand. Significant bilateral sensory deficits (88.8%) were ascertained in hemiplegic children (P < .05), when compared to the performance of the healthy controls. Stereognosis and proprioception were the chief modalities affected bilaterally. The extent of sensory loss did not mirror the severity of motor deficit. Conversely, findings on somatosensory evoked potentials were closely related to motor function. Thus, a clinical sensory evaluation should be an integral part of the assessment of children with cerebral palsy. The likelihood of sensory impairment in one or more modalities on the hemiplegic or nonhemiplegic side is underappreciated and needs to be identified by rehabilitation specialists to maximize the functional potential of these children.

Home testing for pediatric obstructive sleep apnea syndrome secondary to adenotonsillar hypertrophy.

Abstract: The objective of this study was to determine the accuracy and practicality of home testing for pediatric obstructive sleep apnea syndrome (OSAS) secondary to adenotonsillar hypertrophy. Twenty-one children aged 2-12 years and referred for possible OSAS were studied twice, once at home and once in the sleep laboratory. The home test consisted of two parts: (1) a cardiorespiratory recording of saturation (SaO2), pulse rate, pulse waveform, electrocardiogram, and respiratory inductive plethysmography; and (2) an 8-hour videotape recording of the sleeping child. In the laboratory, standard nocturnal polysomnography including electroencephalography was performed. Experiences with another 62 children who underwent home testing alone were also reviewed and are reported. At home, saturation, respiratory, and video data were obtained 96.4 ± 13.3% (mean ± SD) 99.4 ± 1.6%, and 90.0 ± 7.8% of the time, respectively. The sleep efficiency was greater at home than in the laboratory, 91.1 ± 3.9% vs. 86.1 ± 7.2%, with a mean difference of 5.0% (P < 0.01). The median environmentally induced movement/arousal index was lower in the home than in the laboratory, 0.0 (inter-quartile range, 0.0-0.3) vs. 2.4/hr (inter-quartile range 1.2–4.2), with a median difference of 2.4/hr (P < 0.001). Study duration, apne/dhypopnea index, desaturation index, respiratory and spontaneous movement/arousal indices, and oxygen saturation during sleep were similar for home and laboratory studies. Although neither sleep state nor PCO2, (transcutaneous or end-tidal) was measured in the home, this information would have modified patient management in, at most, one case. In the second group of 62 children, exclusively studied at home, all studies were successfully recorded despite a wide range of sleep efficiencies, apne/dhypopnea indices, and desaturation indices. We conclude that home testing, using a simplified cardiorespiratory montage plus video recording, is accurate and of practical use in the routine evaluation of OSAS in patients with adenotonsillar hypertrophy. Pediatr Pulmonol. 1995; 20:241–252. © 1995 Wiley-Liss, Inc.

Synovial hemangioma: imaging features in eight histologically proven cases, review of the literature, and differential diagnosis

Abstract: This study was undertaken to describe the imaging characteristics of synovial hemangioma, with the goal of improving the disappointing rate (22%) of clinical diagnosis of this condition. A review of the literature and the differential diagnosis of intra-articular lesions, including synovial osteochondromatosis and pigmented villonodular synovitis, are also presented. The subjects of the study were 8 patients (4 males, 4 females; age range: 5–47 years; mean age: 19 years) with histologically confirmed synovial hemangioma involving the knee (n=7) or wrist (n=1). We retrospectively examined the imaging studies performed in these patients, including plain radiography (n=8), magnetic resonance imaging (MRI; n=4), angiography (n=3), arthrography (n=2), and contrast-enhanced computed tomography (CT; n=2). Plain radiographs showed a soft tissue density suggesting either joint effusion or a mass in all patients. Phleboliths and bone erosions on plain films in four patients with extra-articular soft tissue involvement pointed to the correct diagnosis. Angiography, showing fine-caliber, smooth-walled vessels, contrast pooling in dilated vascular spaces, and early visualization of venous structures, was diagnostic in two patients. Neither arthrography nor CT yielded specific enough findings. MRI was consistently effective in allowing the correct diagnosis to be made preoperatively, showing an intra-articular or juxta-articular mass of intermediate signal intensity on T1-weighted images and of high signal intensity on T2or T2*-weighted images with low-signal channels or septa within it. A fluid-fluid level was found in two patients with a cavernous-type lesion. Despite the limited nature of this study, it shows clearly that MRI is the procedure of choice whenever an intra-articular vascular lesion such as synovial hemangioma is suspected. Nonetheless, phleboliths and evidence of extra-articular extension on plain radiographs point to angiography as an effective procedure of first resort because it can be combined with embolotherapy.

The management of chylothorax/chylopericardium following pediatric cardiac surgery: a 10-year experience.

Abstract: We reviewed the management of 25 cases of chylothorax/chylopericardium (CT/CP) in 24 patients (9 females, 15 male; 3 days to 11-years-old) following 1605 cardiothoracic procedures (incidence of 1.5%) between January 1984 and December 1993 at our institution. The surgical procedures preceding the occurrence of lymph leak included ligation of patent ductus arteriosus (6 patients), coarctation/double aortic arch repairs (3), complex intracardiac repairs (11), and systemic to pulmonary shunts (5). There were 3 CPs and 22 CTs. All of the patients were initially treated nonsurgically with diet modification using either total parenteral nutrition (TPN) or enteral low fat solid food or enteral elemental diet supplemented with intravenous lipid emulsion. Twenty-one cases (84%) responded to conservative therapy. Of those, 15 had TPN as the initial treatment; the average duration of lymph leak was 13.7 (range 7 to 30) days and the average maximal lymph leak was 39.4 (range 15 to 130) mL/kg per day. The other six cases had low-fat enteral diet as the initial treatment, four resolved completely. Two with high-central venous pressure had to be switched to TPN prior to complete resolution. The average duration of lymph leak in this subgroup was 30 (range 12 to 56) days with the average maximal lymph leak was 30.1 (range 8.5 to 59) mL/kg per day. Excluding these two cases, the average lymph leak of the rest of the group was very compatible to the TPN group of 15 days. Lymphocytopenia and hyponatremia were frequently seen during CT/CP (47.6% and 43%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Isolation of a cDNA encoding human holocarboxylase synthetase by functional complementation of a biotin auxotroph of Escherichia coli

Abstract: Holocarboxylase synthetase (HCS) catalyzes the biotinylation of the four biotin-dependent carboxylases in human cells. Patients with HCS deficiency lack activity of all four carboxylases, indicating that a single HCS is targeted to the mitochondria and cytoplasm. We isolated 21 human HCS cDNA clones, in four size classes of 2.0-4.0 kb, by complementation of an Escherichia coli birA mutant defective in biotin ligase. Expression of the cDNA clones promoted biotinylation of the bacterial biotinyl carboxyl carrier protein as well as a carboxyl-terminal fragment of the alpha subunit of human propionyl-CoA carboxylase expressed from a plasmid. The open reading frame encodes a predicted protein of 726 aa and M(r) 80,759. Northern blot analysis revealed the presence of a 5.8-kb major species and 4.0-, 4.5-, and 8.5-kb minor species of poly(A)+ RNA in human tissues. Human HCS shows specific regions of homology with the BirA protein of E. coli and the presumptive biotin ligase of Paracoccus denitrificans. Several forms of HCS mRNA are generated by alternative splicing, and as a result, two mRNA molecules bear different putative translation initiation sites. A sequence upstream of the first translation initiation site encodes a peptide structurally similar to mitochondrial presequences, but it lacks an in-frame ATG codon to direct its translation. We anticipate that alternative splicing most likely mediates the mitochondrial versus cytoplasmic expression, although the elements required for directing the enzyme to the mitochondria remain to be confirmed.

Neonatal hydronephrosis—the controversy and the management

Abstract: Neonatal hydronephrosis is being detected with increasing frequency. The majority of these cases have a tendency to resolve during infancy. Hydronephrosis is an anatomical entity that is not synonymous with obstruction. Review of the pathoembryology, the pathophysiology, the diagnostic techniques currently used and the natural history of hydronephrosis is given. The management and the controversies involved are discussed.

Do High Doses of Stimulants Impair Flexible Thinking in Attention-Deficit Hyperactivity Disorder?

Abstract: Objective To test the hypothesis that high doses of methylphenidate (MPH) impair cognitive flexibility in attention-deficit hyperactivity disorder (ADHD). Method: A double-blind crossover design was used in an acute dosage trial to assess effects of three dosages (0.3, 0.6, and 0.9 mg/kg) of MPH on the performance of 17 ADHD children on five tasks designed to assess divergent thinking, perseveration, and ability to shift mental set. The tasks also assessed convergent thinking, problem solving, and speed and accuracy of processing. Results There was minimal evidence of deleterious effects on flexible thinking or other cognitive processes, either in the ADHD group as a whole or in any subgroup. The most common pattern indicated linear improvement across dosages. Conclusions Under the acute dosage conditions used in this study, MPH doses up to 0.9 mg/kg had an increasingly positive effect on measures of mental flexibility and other cognitive processes. Rather than eliciting perseveration, MPH appeared to improve persistence. The generalized nature of the cognitive and motivational changes observed suggests that MPH acts on central, self-regulatory processes. Because effects of two or more daily doses can accumulate when MPH is prescribed in the clinical situation, clinical doses of more than 0.6 mg/kg were not recommended. J. Am. Acad. Child Adolesc. Psychiatry, 1995, 34, 7:877–885.

Right-hemisphere dysfunction in Asperger's syndrome.

Abstract: Asperger's syndrome has many clinical features in common with acquired right-hemisphere dysfunction and has been postulated to result from a developmental abnormality of the right hemisphere. However, right-hemisphere abnormality has not previously been documented on neuroanatomic or functional imaging in patients with Asperger's syndrome. We report three patients with Asperger's syndrome found to have abnormal right-hemisphere function on single photon emission computed tomographic (SPECT) imaging. The subjects were two males and one female, ranging from 12 to 16 years of age. All were diagnosed on the basis of the presence of the complete constellation of clinical features previously outlined. All patients were investigated with computed tomographic (CT) scanning, magnetic resonance imaging (MRI), and SPECT scanning. In one subject, CT and MRI revealed enlargement of the right lateral ventricle, reflecting a mild degree of right hemispheric atrophy. CT and MRI studies on the other two subjects were normal. SPECT scanning demonstrated right hemispheric abnormalities in each subject: right temporal hypoperfusion with a central area of increased perfusion along with frontal polar hyperperfusion in one; diffusely decreased right hemispheric uptake in the second; and decreased frontal and occipital uptake in the third. Cerebellar abnormalities were also present: a smaller right hemisphere with increased uptake in the first; decreased uptake in the vermis and right hemisphere in the second; and decreased vermal uptake in the third. These findings support the hypothesis that the neurobiologic basis of Asperger's syndrome is a developmental abnormality of the right cerebral hemisphere.

Social policy as a cause of childhood accidents: the children of lone mothers.

Abstract: Almost one in five British mothers is a lone mother. Their children have injury rates that are twice those of children in two parent families. In this article the link between lone parenthood and childhood injury is examined. The increased injury rates for the children of lone mothers can be explained by the poverty, poor housing conditions, and social isolation of lone mothers in Britain. The problem of reconciling the demands of paid work with the demands of the unpaid work of childrearing is particularly difficult for lone mothers, who find themselves in a benefit dependent poverty trap. Many such mothers would seek paid work if affordable day care were available. Day care would also provide a safe environment for their children, who are otherwise exposed to the environmental hazards of poor housing. Provision of day care is a social policy that would have important effects on the health and welfare of lone mothers and their children. These effects deserve to be properly evaluated. Since the early 1970s the number of one parent families in Britain has increased by between 30000 and 40000 a year. Currently there are over one million lone parent families in Britain, about 21% of all families with children. Nine out of 10 of these families are headed by a mother.1 The children of lone mothers have the highest death rates of all social groups. In a reanalysis of British census data, the children of “unoccupied” parents, of whom an estimated 89% are unemployed single mothers, had a death rate 42% higher than children in social class V, the poorest socioeconomic group.2 Injuries were responsible for 60% of the deaths among the children of lone mothers.2 The strong association between single parenthood and risk of childhood injury is well established from epidemiological studies. …

Reproducibility of electroretinograms recorded with DTL electrodes

Abstract: The purpose of this study was to examine whether the use of the DTL fiber electrode yields stable and reproducible electroretinographic recordings. To do so, luminance response function, derived from dark-adapted electroretinograms, was obtained from both eyes of 10 normal subjects at two recording sessions spaced by 7–14 days. The data thus generated was used to calculate Naka-RushtonVmax andk parameters and values obtained at the two recording sessions were compared. Our results showed that there was no significant difference in the values ofVmax andk calculated from the data generated at the two recording sessions. The above clearly demonstrate that the use of the DTL fiber electrode does not jeopardize, in any way, the stability and reproducibility of ERG responses.

Effects of morphine, pentobarbital and amphetamine on formalin-induced behaviours in infant rats: sedation versus specific suppression of pain.

Abstract: The behavioural response of infant rats to intraplantar injection of formalin consists of specific directed behaviours (limb flexion, shaking and licking the injected paw) and non-specific behaviours that are also induced by non-nociceptive stimulation (squirming, hind limb kicks and whole body jerks), with specific indicators becoming more frequent as pups mature. The present study examined the effects of systemic morphine, pentobarbital and D-amphetamine on formalin-induced behaviours and behavioural state in rat pups from 1 to 20 days of age. Morphine (1 mg/kg) almost completely suppressed both specific and non-specific indicators of pain, and produced mild sedation relative to handled control pups. Pentobarbital (10 mg/kg) produced a similar degree of sedation and suppression of non-specific measures as morphine, but only had weak effects on specific measures in pups less than 1 week old, and no effects thereafter. Suppression of both specific and non-specific pain measures after amphetamine (2 mg/kg) emerged during the 2nd week of life and was not associated with sedation. Thus, morphine produced behavioural analgesia in infant rats in a model of injury-induced inflammatory pain from the 1st postnatal day, when their neurological maturity is similar to a 25-week human fetus, and 1 week before antinociception is observed in thermal and pressure tests. The effects of morphine were qualitatively different from a sedative dose of pentobarbital. The data support the contention that opioids have specific analgesic effects in premature human neonates and underline the need for pain measures that discriminate between sedation and analgesia.

Alveolar cleft bone grafts: results and imprecisions of the dental radiograph.

Abstract: Alveolar cleft bone grafts customarily have been evaluated by one-dimensional dental radiographic measurements. Based on the dental radiograph, remarkable successes with just a single bone graft have been reported in the literature. At the Montreal Children's Hospital, the experience with 101 alveolar bone grafts in 62 cleft lip and palate patients was retrospectively reviewed to determine (1) the precision of dental radiographs at evaluating the clinical outcome, (2) the effect of dental maturation on alveolar bone grafts, and (3) the effect of augmentation bone grafts. The dental radiograph significantly overestimated the number of clefts that could be managed orthodontically (p < 0.01, McNemar's test) and thus poorly prognosticated the ability to achieve bony obliteration of the alveolar cleft and orthodontic closure of the dental gap. Bone grafts performed during the preeruptive canine dentition yielded significantly better results (p < 0.05, chi-squared test). With each subsequent augmentation bone-graft procedure performed, there existed a trend toward improved dental arch stability and radiographic and clinical outcomes.

Regulated synthesis and localization of DNA methyltransferase during spermatogenesis.

Abstract: Differences in the methylation patterns of male and female gamete DNA are likely to be involved in genomic imprinting. However, little is known of the mechanisms that regulate de novo methylation and demethylation during gametogenesis. We report here that the well-characterized M(r) 190,000 form of DNA methyltransferase (the only known form) is present in isolated mitotic, meiotic, and postmeiotic male germ cells, with the exception of meiotic pachytene spermatocytes, where the protein is undetectable by immunoblot analysis and a novel 6.2-kb DNA methyltransferase transcript is present. Whereas replication and methylation are coupled in somatic cells, the presence of DNA methyltransferase in postreplicative male germ cells is consistent with previously observed de novo methylation events in these cells. Immunofluorescence experiments revealed that DNA methyltransferase is localized to the nuclei of male germ cells, with a subset of spermatogonia and postreplicative leptotene/zygotene spermatocytes displaying prominent nuclear foci that are strongly enriched in DNA methyltransferase. The data suggest that down-regulation of DNA methyltransferase expression during the pachytene stage of meiosis utilizes an mechanism that is associated with the production of a larger mRNA, and that de novo methylation in leptotene/zygotene spermatocytes may take place in spatially restricted nuclear domains that are enriched in DNA methyltransferase.

Characterization of endothelin receptors in newborn piglet lung.

Abstract: Endothelins (ET-1, ET-2, and ET-3) cause dilation and constriction as a result of binding to different ET receptors. ET A receptor is responsible for the vasoconstrictor response, while ET B receptors lead to vasodilation (ET B1 ) or vasoconstriction (ET B2 ). Although the effects of ETs have been described in the neonatal pulmonary vasculature, ET receptors have not been characterized extensively. Therefore, in newborn piglets we aimed to characterize ET receptors by studying 1) in isolated perfused lungs the effects of ET-1, ET-3, and the ET B receptor agonists sarafotoxin S6c (S6c) and BQ-3020 on perfusion pressure with or without an ETA antagonist, BQ-123, or an ET B1 antagonist, RES-701-1, and 2) the concentrationdependence of ET-1 and ET-3 on their binding to microsomes from arteries and veins of piglet lungs. ET-1, ET-3, S6c, and BQ-3020 cause an early-onset dilation followed by a late-onset constriction. The dilator response to ET-3 is blunted by RES-701-1 (P < 0.005), while the inhibition of the dilator response of ET-1 almost reaches significance (P = 0.06). BQ-123 inhibits incompletely (P < 0.05) the constrictor response to ET-1, while it does not alter the response to ET-3. This suggests that constriction may follow binding to ET A as well as ET B2 receptors. Binding studies reveal that ET receptors are abundant in pulmonary vessels. ET A receptors are predominant, but ET B1 and likely ET B2 receptors are also present. Also, receptor affinities are higher in veins than in arteries. Thus vasodilation follows binding to ET B1 receptors, and vasoconstriction, to ETA and likely ETaz receptors. Tissue differences in receptor affinity suggest that ET-1 may be morepotent in veins than arteries and that ET receptor expression may be tissue specific. Finally, the high number of binding sites suggests that ET plays a role in the control of vascular tone in the newborn piglet lung

Juvenile spondyloarthropathies: clinical manifestations and medical imaging.

Abstract: The spondyloarthropathies comprise four distinct entities — ankylosing spondylitis, psoriatic arthritis, the arthritis associated with inflammatory bowel disease, and Reiter's syndrome and other related forms of reactive arthritis. Although these are distinct diseases, they have a number of clinical, radiologie, and genetic characteristics in common which permit them to be classified under the unifying term “spondyloarthropathy”. They are diseases of young adults, and when they present in patients under 16 years of age we refer to them as the “juvenile” spondyloarthropathies. They must be distinguished from juvenile rheumatoid arthritis, which is a totally separate entity; however the distinction may not always be obvious. Involvement of peripheral and sacroiliac joints commonly occurs in the juvenile spondyloarthropathies. The peripheral arthritis may be erosive and associated with bone apposition at the joint margins. Axial involvement is usually a late finding. Dactylitis and tenosynovitis are frequently present early on. Enthesitis, a highly specific feature, occurs much more often in the juvenile spondyloarthropathies than in the adult forms and it may be the only presenting feature. The plain radiograph is the primary and most important imaging modality for the assessment of these diseases. However, an expanding role of magnetic resonance imaging is evident.

Trimethylaminuria, fish odour syndrome: a new method of detection and response to treatment with metronidazole.

Abstract: Trimethylaminuria is an autosomal recessive disorder involving deficient N-oxidation of the dietary-derived amine trimethylamine (TMA). TMA, a volatile tertiary amine, accumulates and is excreted in urine of patients with deficient TMA oxidase activity. Treatment strategies for this condition are limited. We report a new stable-isotope dilution method for rapid sequential analysis of TMA concentrations and the clinical and biochemical response to treatment with metronidazole.

Long-term alterations in growth hormone and insulin secretion after temporary dietary protein restriction in early life in the rat

Abstract: Protein malnutrition early in life stunts subsequent physical growth in both humans and rats, but the mechanism(s) is unknown. To test the hypothesis that temporary early life dietary protein restriction produces long-term alterations in the growth hormone (GH) neuroendocrine axis, we examined the effects of 3 wk of exposure to dietary protein restriction in male rats postweaning (3-6 wk of age) on spontaneous and GH-releasing factor (GRF)-stimulated GH secretion at 12 wk of age. In comparison to rats weaned onto a normal diet (23% protein), rats weaned onto a low (4%) protein diet failed to catch up growth when transferred to the normal diet between 6 and 12 wk of age. Spontaneous 6-h GH secretory profiles of adult rats fed the low protein diet early in life showed a 41% reduction in mean GH peak amplitude and a significant suppression in overall mean 6-h plasma GH concentrations (37.5 +/- 4.5 versus 56.9 +/- 5.9 micrograms/L; p < 0.02). The magnitude of the GH response to 1 microgram of rat GRF(1-29)NH2 i.v. challenge was augmented during the GH trough period in these rats (165.7 +/- 30.4 versus 43.9 +/- 17.6 micrograms/L; p < 0.01). Although basal plasma IGF-I levels and glucose tolerance of protein-deprived rats were normal at 12 wk of age, the insulin response to ip glucose was severely blunted [insulin integrated area under the curve: 303.0 +/- 32.7 versus 778.3 +/- 105.0 pmol/L/75 min; p < 0.01]. These results demonstrate that temporary protein malnutrition early in life 1) blunts spontaneous pulsatile GH secretion, 2) augments GH responsiveness to GRF challenge, and 3) reduces the insulin secretory response to glucose in adulthood. Our findings suggest that dietary protein in early life is an important determinant for CNS control of GH secretion as well as for the development of pancreatic beta-cell sensitivity to glucose. Such alterations in the GH neuroendocrine axis, together with the subnormal insulin secretion, likely contribute to the lack of catch-up growth in this model.

Effect of P(i) restriction on renal Na(+)-P(i) cotransporter mRNA and immunoreactive protein in X-linked Hyp mice

Abstract: Although renal Na + -P i cotransporter gene expression is decreased in X-linked Hyp mice, the mutants do respond to P i restriction with an adaptive increase in Na + -P i cotransport maximal velocity in renal brush-border membrane vesicles. In the present study, we examined the mechanism for the adaptive increase in Na + -P i cotransport in P i -deprived Hyp mice and normal littermates, using a cDNA probe encoding a rat, renal-specific Na + -P i cotransporter (NaPi-2) and a rabbit polyclonal antibody raised against a synthetic NaPi-2-derived peptide. The low-P i diet elicited an increase in Na + -P i cotransport in normal (141 ± 13 to 714 ± 158) and Hyp mice (59 ± 6 to 300 ± 62 pmol-mg protein −1 .6 s −1 ; means ± SE, n = 3, P < 0.01) that was accompanied by an increase in brush-border membrane NaPi-2 protein, relative to ecto-5'-nucleotidase, in normal (1.0 ± 0.1 to 7.6 ± 1.5) and Hyp mice (0.3 ± 0.1 to 7.7 ± 1.4) (means ± SE, n = 4; P < 0.01). THE LOW-P i diet also elicited an increase in the abundance of NaPi-2 mRNA, relative to the 18S RNA, in normal (157 ± 9% of control diet, P < 0.05) and Hyp mice (194 ± 10% ofcontrol diet, P < 0.01). Immunohistochemistry revealed that NaPi-2 protein was localized to the brush-border membrane of the proximal tubule and that both intensity of the signal and number of immunostained proximal tubules were increased in renal sections from normal and Hyp mice fed the low-P i diet. In summary, 1) the adaptive increase in Na + -P i cotransport is the result of an increase in NaPi-2 mRNA and protein in both P i -deprived normal and Hyp mice; 2) abundance of NaPi-2 protein is similar in both mouse strains following P i deprivation, despite persistence of the P i transport defect in Hyp mice under these conditions; and 3) the increase in NaPi-2 protein far exceeds the increase in NaPi-2 mRNA, suggesting that translational and/or posttranslational mechanisms play a significant role in the adaptive response to P i restriction

Late pulmonary function following repair of tracheoesophageal fistula or esophageal atresia.

Abstract: Although tracheoesophageal fistula and esophageal atresia (TEF-EA) are surgically correctable, late respiratory complications have been reported. We administered a respiratory and gastrointestinal symptom questionnaire and performed standard pulmonary function tests (PF T's) and methacholine challenge testing on an unselected group of 25 subjects with TEF-EA who underwent surgery at our institution between 1963 and 1985. Results were compared to predicted normals, as well as 10 sibling controls. While the mean values of lung function test results for the TEF-EA group were within the normal range, they were significantly different from their siblings. Thirteen of the 25 TEF-EA group (52%), but none (0%) of the controls, had abnormal pulmonary function. This was classified as restrictive in 9 (36%), obstructive in 3 (12%), and mixed in 1. In addition, airway hyperreactivity [defined as a positive methacholine challenge (PC20 < or = 8 mg/mL)], was found in 6 of 18 TEF-EA subjects and 4 of the 9 controls who were evaluated. Comparison of TEF-EA subjects with normal and abnormal PFTs showed no difference in the incidence of tracheomalacia, esophageal strictures or dilatation, recurrent pneumonias, or gastroesophageal reflux. The respiratory symptom score in the subjects and controls was similar, and did not correlate with abnormal pulmonary function. The cause of the pulmonary function abnormalities remains unexplained.

Lesionectomy of MRI Detected Lesions in Children with Epilepsy

Abstract: The results of complete excision of cerebral lesions detected by MRI in 18 children presenting with epilepsy were analyzed. There were 14 boys and 4 girls with a mean age of 9.2 years. The average age of onset of seizures was 6.8 years. The mean time from onset of seizures to surgery was 2.3 years. Often, CT scans suggested that the lesions were indolent. MRI was better in differentiating neoplastic from developmental lesions. Angiography was non-contributory in this series. Interictal EEGs showed epileptiform activity correlating with imaging studies in 54% of children. The lesion was completely surgically excised in all patients. This was confirmed by intra-operative ultrasound and postoperative imaging. Electrocorticography was performed prior to and after the resection, but residual spiking did not lead to further resection. The average postoperative follow-up was 5.7 years. Five patients had low grade astrocytomas, 4 had gangliogliomas, 1 a mixed astrocytoma-oligodendroglioma, 3 had cortical dysplasia, 2 infantile desmoplastic gangliogliomas, 2 hamartomata, and 1 cavernous angioma. Sixteen patients have been seizure-free since surgery. Only 2 have partial seizures. Thus, all patients benefited from the resection, with respect to seizure control. In those with temporal lobe lesions, improvement in IQ was seen postoperatively. Early consideration of surgery in patients with epilepsy and lesions demonstrated by MRI is suggested.

Negative-pressure hydrocephalus

Abstract: ✓ Two cases of children with closed myelodysplasia, Arnold-Chiari malformation, and shunted hydrocephalus who underwent spinal arachnoid cystopleural shunting are presented. Postoperatively, both patients developed craniovertebral symptomatology accompanied by radiologically documented ventricular dilation in spite of negative intracranial pressure and functional ventriculoperitoneal (VP) shunts. Both patients recovered after the cystopleural shunts were revised to increase the resistance to flow within the system. The authors believe that some communication between the arachnoid cyst and the subarachnoid space existed in both cases and that the negative pleural pressure was transmitted preferentially to the spinal and cerebral convexity subarachnoid spaces with relative sparing of the ventricular system. A transmantle pressure gradient was thereby established, leading to ventricular dilation. The authors further suggest that a craniospinal gradient was possibly established as well, leading to cranioverte...