Biomedical subjects

C Stanley

Publications and source records attributed to C Stanley.

At least 19 recordsLinked to original sources

PubMed2006

The influence of previous exposure to environmental mycobacteria on the interferon-gamma response to bacille Calmette-Guérin vaccination in southern England and northern Malawi.

We report a large study of the effect of BCG vaccination on the in vitro 6-day whole blood interferon-gamma (IFN-gamma) response to antigens from eight species of mycobacteria among schoolchildren in south-eastern England, where bacille Calmette-Guérin (BCG) vaccination is highly protective against pulmonary tuberculosis, and among young adults in northern Malawi, where BCG vaccination is not protective. In the UK children, BCG induced an appreciable increase in IFN-gamma response to antigens from most species of mycobacteria. The degree of change was linked to the relatedness of the species to Mycobacterium bovis BCG, and provides further evidence of the cross-reactivity of mycobacterial species in priming of the immune system. IFN-gamma responses to purified protein derivatives (PPDs) from M. tuberculosis and environmental mycobacteria were more prevalent in the Malawian than the UK group prior to vaccination; BCG vaccination increased the prevalence of responses to these PPDs in the UK group to a level similar to that in Malawi. There was no evidence that the vaccine-induced change in IFN-gamma response was dependent upon the magnitude of the initial response of the individual to environmental mycobacteria in the United Kingdom or in Malawi. These observations should assist the development and interpretation of human clinical trials of new vaccines against M. tuberculosis in areas of both low and high exposure to environmental mycobacteria.

Adolescent↗

PubMed2005

Dominantly inherited hyperinsulinaemic hypoglycaemia.

Congenital hyperinsulinism (HI), the most important cause of hypoglycaemia in early infancy, is a heterogeneous disease with two types of histological lesions, focal and diffuse, with major consequences in terms of surgical approaches. In contrast to focal islet-cell hyperplasia, always sporadic to our knowledge, diffuse hyperinsulinism is a heterogeneous disorder involving several genes, various mechanisms of pathogenic mutations and different transmissions: (i) channelopathy involving the genes encoding the sulphonylurea receptor (SUR1) or the inward-rectifying potassium channel (Kir6.2) in recessively inherited HI or more rarely dominantly inherited HI; (ii) metabolic disorders implicating the short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) enzyme inrecessively inherited HI, the glucokinase gene (GK), the glutamate dehydrogenase gene (GLUD1) when hyperammonemia is associated, dominant exercise-induced HI with still-unknown mechanism, and more recently the human insulin receptor gene in dominantly inherited hyperinsulinism. Thus, dominant HI disorders always correspond to diffuse HI, where most hypoglycaemia occur in infancy, and are sensitive to medical treatment. Channel causes could be due to dominant negative mutation with one abnormality in channels composed of four Kir6.2 subunits and four SUR1 subunits, leading to a complete destruction of the channel structure or function, or due to haploinsufficiency with only one functional allele, leading to 50% of functional protein, which is not sufficient to obtain enough opened channels to maintain the membrane depolarized. Metabolic causes are due to a gain of function of enzyme activity (deregulated enzymes), except for physical exercise-induced hyperinsulinaemic hypoglycaemia, of still-unknown cause. Congenital hyperinsulinism (HI) is the most important cause of hypoglycaemia in early infancy (Aynsley-Green et al 2000; Cornblath et al 1990; Pagliara et al 1973; Thomas et al 1977). The inappropriate oversecretion of insulin is responsible for profound hypoglycaemia that requires aggressive treatment to prevent severe and irreversible brain damage (Volpe 1995). HI is a heterogeneous disease associated with several genes, various mechanisms of pathogenic mutations and different transmissions (Dunne et al 2004).

Exercise↗

PubMed2004

Glutamate and tachykinin receptors in central sensitization of withdrawal reflexes in the decerebrated rabbit.

This study assessed the involvement of NMDA and group I metabotropic glutamate receptors, and tachykinin NK1 and NK3 receptors, in central sensitization of withdrawal reflexes in the decerebrated rabbit. Reflexes evoked in the ankle flexor tibialis anterior and the knee flexor semitendinosus by electrical stimulation at the base of the toes were enhanced for 29-63 min after application of 20% mustard oil to the tips of the toes. Selective antagonists of mGlu1, mGlu5, NMDA and NR2B-subunit-containing NMDA glutamate receptors, as well as NK1, and NK3 receptors, and a non-selective blocker of all tachykinin receptors, were assessed for their effects on the magnitude and duration of the increase in reflexes induced by mustard oil. Dizocilpine, an antagonist of all NMDA receptors (1 mg intrathecal) abolished facilitation of tibialis anterior reflexes and significantly reduced the magnitude and duration of increase of the semitendinosus response. The NR2B-subtype selective antagonist CP-101,606 decreased the magnitude of facilitation of both reflexes but had no effect on duration of enhancement. Selective antagonists for the mGlu1 (CPCCOEt, 1-3 mg intrathecal), mGlu5 (MPEP, 0.2-1 mg intrathecal), NK1 (L-733,060, 0.3 mg intrathecal) or NK3 (SR 142,801, 1 mg kg(-1) i.v.) receptors had no effect on the amplitude or duration of sensitization. However, the non-selective tachykinin receptor blocker ZD-6021 (0.3 mg intrathecal) reduced the amplitude but not the duration of sensitization in the flexor reflexes. Combination of ZD-6021 with CP-101,606 (doses as above) decreased both aspects of the sensitization response. Dizocilpine reduced reflexes evoked from the heel per se, and dizocilpine, CP-101,606 and ZD-6021 reduced arterial blood pressure. Otherwise the drugs used had no effects on baseline variables. The present data confirm the importance of NMDA receptors as a critical part of the process of central sensitization, provide no evidence for a role of metabotropic glutamate receptors, and show that simultaneous blockade of all tachykinin receptors is required to reveal their role in hyperalgesia. The data further indicate that a combined pharmacological approach offers a potential way forward for the development of new antihyperalgesic agents.

Animals↗

PubMed2003

Interferon-gamma and skin test responses of schoolchildren in southeast England to purified protein derivatives from Mycobacterium tuberculosis and other species of mycobacteria.

The immune responses of schoolchildren in southeast England to Mycobacterium tuberculosis and other species of mycobacteria were studied prior to vaccination with bacille Calmette-Guérin (BCG). Data are presented for tuberculin (Heaf) skin test and interferon-gamma (IFN-gamma) responses to M. tuberculosis purified protein derivative (PPD), and IFN-gamma responses to PPDs from eight other environmental mycobacteria, measured in 424 schoolchildren (13-15 years of age). Responses to M. tuberculosis PPD were detected in 27% of schoolchildren by in vitro IFN-gamma response and in 20% by the Heaf test. IFN-gamma responses were more prevalent to PPDs from species of mycobacteria other than M. tuberculosis, predominantly those of the MAIS complex and M. marinum (45-60% responders). Heaf test and IFN-gamma responses were associated (P<0.001) for M. tuberculosis, MAIS and M. marinum. These findings have implications for appropriate implementation of vaccination against tuberculosis.

Adolescent↗

PubMed2001

Neonatal electroencephalogram does not predict cognitive and academic achievement scores at early school age in survivors of neonatal extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation is an effective rescue treatment for severe cardiorespiratory failure in term or near-term neonates, although a wide range of neurologic sequelae have been noted in a substantial minority of survivors. The objective of the present study was to determine the value of the neonatal electroencephalogram (EEG) for predicting Wechler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), Wide Range Achievement Test, and Wide Range Assessment of Memory and Language scores at early school age in 66 testable survivors of extracorporeal membrane oxygenation who were not severely brain damaged. Technically satisfactory EEG recordings were obtained at least twice following admission to our nursery and prior to discharge. The EEGs were classified and graded according to standard criteria. The developmental test results of those who had only normal or mildly abnormal neonatal EEGs (group 1, n = 9) were compared with those who had at least one moderately or markedly abnormal recording (group 2, n = 57). School-age test and subtest scores were not statistically significantly worse in group 2 versus group 1 infants. No child in group 1 and five children in group 2 had WPPSI-R Full-Scale IQ scores of less than 70. Of the nine children in group 2 who had at least one markedly abnormal neonatal EEG recording (graded as burst suppression or as electrographic seizure), only two had abnormally low WPPSI-R Full-Scale IQ scores. We conclude that EEG recordings obtained during the neonatal course of neonates treated with extracorporeal membrane oxygenation do not predict cognitive and academic achievement test results in survivors at early school age who were testable and not severely brain damaged.

Brain Damage, Chronic↗

PubMed2001

Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients.

Hyperinsulinism and hyperammonemia syndrome has been reported as a cause of moderately severe hyperinsulinism with diffuse involvement of the pancreas. The disorder is caused by gain of function mutations in the GLUD1 gene, resulting in a decreased inhibitory effect of guanosine triphosphate on the glutamate dehydrogenase (GDH) enzyme. Twelve unrelated patients (six males, six females) with hyperinsulinism and hyperammonemia syndrome have been investigated. The phenotypes were clinically heterogeneous, with neonatal and infancy-onset hypoglycemia and variable responsiveness to medical (diazoxide) and dietary (leucine-restricted diet) treatment. Hyperammonemia (90-200 micromol/L, normal <50 micromol/L) was constant and not influenced by oral protein, by protein- and leucine-restricted diet, or by sodium benzoate or N-carbamylglutamate administration. The patients had mean basal GDH activity (18.3 +/- 0.9 nmol/min/mg protein) not different from controls (17.9 +/- 1.8 nmol/min/mg protein) in cultured lymphoblasts. The sensitivity of GDH activity to inhibition by guanosine triphosphate was reduced in all patient lymphoblast cultures (IC(50), or concentrations required for 50% inhibition of GDH activity, ranging from 140 to 580 nM, compared with control IC(50) value of 83 +/- 1.0 nmol/L). The allosteric effect of ADP was within the normal range. The activating effect of leucine on GDH activity varied among the patients, with a significant decrease of sensitivity that was correlated with the negative clinical response to a leucine-restricted diet in plasma glucose levels in four patients. Molecular studies were performed in 11 patients. Heterozygous mutations were localized in the antenna region (four patients in exon 11, two patients in exon 12) as well as in the guanosine triphosphate binding site (two patients in exon 6, two patients in exon 7) of the GLUD1 gene. No mutation has been found in one patient after sequencing the exons 5-13 of the gene.

Adolescent↗

PubMed2001

Influence of joint position on electromyographic and torque generation during maximal voluntary isometric contractions of the hamstrings and gluteus maximus muscles.

STUDY DESIGN: Repeated measures analysis of joint angle effects on hip and knee muscle electromyographic (EMG) activity. OBJECTIVES: To simultaneously determine angle-dependent changes in maximal voluntary isometric contraction (MVIC) torque and EMG activity during hip extension and knee flexion. BACKGROUND: Procedures for normalizing EMG data and for determining torque-angle relationships for various joint motions both entail asking subjects to exert an MVIC. The implicit assumption in these paradigms is that magnitude of the EMG response is at a constant, maximum level so that observed angle-dependent variations in torque are due to mechanical factors, such as muscle length and muscle moment arm. METHODS AND MEASURES: Fifty subjects (25 men and 25 women) participated in this study (age, 23.5 +/- 4.6 y; range, 18-38 y). Subjects performed maximal isometric knee flexion at 4 knee angles and maximal isometric hip extension at 4 hip angles. The dependent variables were normalized root-mean-square EMG and torque. The process for normalizing EMG and torque data consisted of determining the largest mean value for each subject across testing positions for the muscle of interest. That value was designated as corresponding to 100% MVIC, and all other data for that muscle were expressed as a percentage of the MVIC value. Repeated measures was used to determine angle-dependent changes in normalized MVIC-torque and MVIC-EMG values for each muscle group. RESULTS: Mean torque-angle relationships were generally consistent with previous reports, though considerable intersubject variability was observed. There were significant angle-dependent differences in maximal EMG for both the hamstring and gluteus maximus muscles. Mean percentages of hamstring MVIC-EMG at knee angles of 30 degrees (81 +/- 19) and 60 degrees (82 +/- 22) were greater than at 0 degrees (68 +/- 20) or 90 degrees (74 +/- 20). The mean percentage of gluteus maximus MVIC-EMG at a hip angle of 0 degrees (94 +/- 10) was greater than at 30 degrees (84 +/- 13), 60 degrees (80 +/- 14), or 90 degrees (64 +/- 20), and gluteus maximus maximal voluntary isometric EMG at 90 degrees was less than at all other angles. These differences could not be explained solely by muscle length-dependent effects on EMG amplitude, suggesting that despite instructions for maximal effort, motor unit activation was not maintained at a constant, maximal level throughout the range of motion. The form of the EMG/angle relationships differed markedly from the torque-angle relationships. CONCLUSIONS: These findings have implications for the use of MVIC-EMG for reference values in EMG normalization procedures and for the interpretation of mechanisms underlying the torque-angle relationships observed in vivo.

Adult↗

PubMed2000

Sources of error when tracking irrigation fluids during hysteroscopic procedures.

STUDY OBJECTIVE: To evaluate the ability of circulating nurses to estimate input and outgo of irrigating fluids used during hysteroscopic procedures in a hospital operating room. DESIGN: Simulation of intraoperative measurements (Canadian Task Force classification II-1). SETTING: Operating room. Intervention. Circulating nurses estimated fluid volumes under circumstances simulating actual conditions of hysteroscopic ablative or resection procedures. MEASUREMENTS AND MAIN RESULTS: Three-liter glycine irrigation bags were overfilled by an average of 2.8% (62-125 ml). Estimates of fluid remaining in partially emptied bags were in error by an average ranging from 4% to 50%/bag (largest error 10-55%, 157-401 ml). Estimates of fluid in kick buckets were in error by an average of 10% to 39% (largest error 22-66%, 232-903 ml). Visual estimates of fluid on the operating room floor were in error by an average of 56% to 67% (largest error 65-81%, 182-840 ml). Estimates of fluid in suction canisters were consistent among nurses. The accuracy of measurements for partially filled suction canisters primarily depended on the accuracy of canister calibration. Volume contained in cascaded suction canisters from an actual surgical procedure was grossly different from rated capacity. CONCLUSION: Accurate tracking of irrigation fluid during hysteroscopic procedures is difficult. Even with a mechanical measuring system, fluid lost on the floor can introduce sizable errors. Estimation errors can easily and quickly accumulate to clinically significant volumes. Use of an automated mechanical fluid-tracking system with devices to capture fluid lost from the surgical field is recommended.

Body Fluids↗

PubMed2000

A new method of evaluating attachment representations in young school-age children: the Manchester Child Attachment Story Task.

We describe a new instrument, using a doll-play vignette completion method, which applies concepts and methodologies from infant and adult attachment research to enable identification and detailed classification of internal representations of attachment relationships in young school-age children. Validation of the Manchester Child Attachment Story Task (MCAST) in a normal population (N = 53) shows good interrater reliability and content validity. Patterns of attachment representation identified show stability over time. Comparisons are made with existing methodologies, and potential applications of the instrument and directions for future research are discussed.

Child↗

PubMed2000

The Manchester Child Attachment Story Task: relationship with parental AAI, SAT and child behaviour.

The Manchester Attachment Story Task (MCAST) is a new method for eliciting the internal working model (IWM) of attachment representations in children between 5 and 7 years. The instrument is described in the companion paper, 'A New Method of Evaluating Attachment Representations'. This paper reports initial findings on a non-clinical sample comparing the MCAST with concurrent maternal attachment representation, measures of child temperament and behaviour, and concurrent ratings on the Separation Anxiety Test (SAT). Ratings of disorganized attachment on the MCAST show association with Unresolved status on concurrent maternal Adult Attachment Interview (AAI) and with independent teacher ratings of classroom behaviour. Child temperament shows an effect on the style of engagement with the interview but not the attachment ratings. Possible alternative explanations for the phenomena seen are discussed, along with potential applications of the instrument and directions for future research.

Anxiety, Separation↗

PubMed1999

Five-year follow-up of neonates with reconstructed right common carotid arteries after extracorporeal membrane oxygenation.

OBJECTIVE: Serial Doppler ultrasonography and long-term neurodevelopmental follow-up outcomes were evaluated prospectively in neonates whose right common carotid artery (RCCA) was reconstructed after extracorporeal membrane oxygenation (ECMO). METHODS: Children with RCCA reconstruction (n = 34) were monitored for 3.5 to 4.5 years by Doppler ultrasonography for arterial patency, and 28 had IQ testing by 5 years. A comparison group consisted of 35 infants who had RCCA ligation after ECMO. Neonatal electroencephalograms and computed tomography/magnetic resonance imaging scans were also compared. RESULTS: Reconstructions were successful (<50% RCCA stenosis by Doppler ultrasonography) in 26 (76%) of 34 children, 3 (9%) had >/=50% stenosis, and 5 (15%) had occlusion. No significant differences were seen between reconstructed and ligated groups in neonatal complications or ECMO courses. Occurrence of marked neonatal electroencephalographic abnormalities did not differ between groups. Abnormalities on computed tomography/magnetic resonance imaging scans (4 of 31 vs 11 of 29, P =.025) and cerebral palsy (0 of 34 vs 5 of 35, P =.054) were more common in infants with RCCA ligation. No differences were seen in developmental or IQ scores between the 2 groups, and 4 in each group had cognitive handicaps (at least 1 IQ score <70). CONCLUSIONS: Most RCCA reconstructions remained patent, with 24% showing significant stenosis or occlusion. Compared with a historical control group, patients with RCCA reconstruction had fewer brain scan abnormalities and tended to be less likely to have cerebral palsy. RCCA reconstruction after venoarterial ECMO may improve outcome.

Birth Weight↗

PubMed1998

Effects of silica exposure on substance P immunoreactivity and preprotachykinin mRNA expression in trigeminal sensory neurons in Fischer 344 rats.

Trigeminal sensory neurons innervate the nasal cavity and may release substance P (SP) upon exposure to inhaled irritants. The purpose of this study was to determine if silica dust, an occupational irritant causing inflammation, activates sensory neurons supplying the nasal cavity. Male Fischer 344 rats were placed in inhalation chambers and exposed daily to 2 mg/m3 of fresh silica (average diameter 1 microm) for 6 mo. Following exposure, the trigeminal ganglia (TG) were removed and prepared for SP immunocytochemistry and for preprotachykinin (PPT) autoradiographic in situ hybridization. The SP-like immunofluorescence in TG neurons was subjectively categorized as high, moderate, or low (background) intensity. In situ hybridization autoradiographs were quantified on the basis of grain density using digital imaging analysis. The SP immunoreactivity and PPT mRNA expression in the TG neurons were significantly increased after silica inhalation. The proportion of highly positive SP-immunoreactive neurons shifted from 1.30 +/- 0.58% in controls to 11.30 +/- 1.15% after silica treatment. The neurons exhibiting high grain density for PPT mRNA increased from 1.50 +/- 0.87% in controls to 11.67 +/- 0.58% in the silica group. Thus, inhalation of silica causes upper airway irritation resulting in increased levels of immunoreactive neuronal SP and PPT mRNA. These findings suggest that silica activates sensory pathways that may be involved in nasal inflammation.

Air Pollutants↗

PubMed1997

Sensitivity and specificity of the neonatal brain-stem auditory evoked potential for hearing and language deficits in survivors of extracorporeal membrane oxygenation.

OBJECTIVE: We determined the sensitivity and specificity of neonatal brain-stem auditory evoked potentials (BAEP) as markers for subsequent hearing impairment and for developmental problems found later in infancy and childhood. METHODS: BAEP studies were performed before discharge in infants treated with extracorporeal membrane oxygenation (ECMO), and two specific abnormalities were analyzed: elevated threshold and delayed central auditory conduction. Behavioral audiometry was repeated during periodic follow-up until reliable responses were obtained for all frequencies, and standardized developmental testing was also conducted. The sensitivity and specificity of an elevated threshold on the neonatal BAEP for detecting subsequent hearing loss, and the relationship of any neonatal BAEP abnormality to language or developmental disorders in infancy, were calculated. RESULTS: Test results for 46 ECMO-treated infants (57.5%) were normal, and those for 34 infants (42.5%) were abnormal, with either elevated wave V threshold, prolonged wave I-V interval, or both on neonatal BAEP recordings. Most significantly, 7 (58%) of the 12 children with subsequent sensorineural hearing loss had left the hospital after showing normal results on threshold tests. There was no significant difference in the frequency of hearing loss between subjects with abnormal (5/21, or 24%) and those with normal BAEP thresholds (7/59, or 12%; Fisher Exact Test, p = 0.28). Therefore the sensitivity of neonatal BAEP testing for predicting subsequent hearing loss was only 42%. Neonatal BAEP specificity for excluding subsequent hearing loss was 76%. In contrast, on language development testing, 19 children demonstrated receptive language delay. Of these children, 12 (63%) had abnormal neonatal BAEP recordings and 7 (37%) had a normal BAEP threshold, normal central auditory conduction test results, or both (p = 0.04). CONCLUSIONS: Neonatal BAEP threshold recordings were of limited value for predicting subsequent hearing loss common in ECMO-treated survivors. However, an abnormal neonatal BAEP significantly increased the probability of finding a receptive language delay during early childhood, even in those with subsequently normal audiometry findings. Because neonatal ECMO is associated with a high risk of hearing and receptive language disorders, parents should be counseled that audiologic and developmental follow-up evaluations in surviving children are essential regardless of the results of neonatal BAEP testing.

Acoustic Impedance Tests↗

PubMed1997

A multimodal, second generation, posttraumatic stress disorder rehabilitation program.

Second Generation posttraumatic stress disorder (PTSD) treatment programs were recently proposed as one component of a model of treatment of chronic PTSD. While First Generation PTSD programs emphasized trauma work, Second Generation programs emphasize skills for the present/future ability to adapt within society. The present paper describes a functioning Second Generation PTSD treatment program for Vietnam combat veterans. The guiding principles underlying this multimodal and vocational rehabilitation program are outlined.

Adaptation, Psychological↗

PubMed1997

Simultaneous 31P MRS of the soleus and gastrocnemius in Sherpas during graded calf muscle exercise.

The observation that the amount of lactate formed during hypobaric hypoxia decreases with the severity of hypoxia has become known as the "lactate paradox." We used noninvasive 31P magnetic resonance spectroscopy (MRS) to further probe this problem and explore the nature of muscle metabolism during rest-exercise-recovery transitions in Sherpas indigenous to the high Himalayas of Nepal. MRS data were obtained using a whole body 1-m bore, 1.5-T Phillips Gyroscan spectrometer. Muscle-specific localization of MRS data acquisition was achieved by means of a modified image-selected in vivo spectroscopy sequence (ISIS). The spectra acquired from the medial and lateral gastrocnemius muscle, rich in fast-twitch fibers, were well constrained by selective excitation and by the boundary of the leg. The spectra from a third region contained signals predominantly from the soleus, a muscle formed mainly of slow-twitch fibers. We quantified relative concentration changes in phosphocreatine (PCr), Pi, and ATP during a series of calf muscle work bouts; free ADP concentrations were calculated on the assumption that the creatine phosphokinase reaction was always essentially at equilibrium. Hydrogen ion concentrations were calculated from the chemical shift of Pi, which represents the equilibrium between mono- and diprotonated phosphate. Plantar flexion was quantified using a calf muscle ergometer designed for operation within a 1-m whole body magnet. We found that the concentration of ATP was rigorously regulated and thus did not change despite large changes in ATP turnover rates required through exercise. The relative concentrations of PCr and Pi were linear functions of the percent maximum work rate of the lateral and medial gastrocnemius, but on transition to exercise the fractional concentration changes in these metabolites were much less than the fractional change in muscle ATP turnover rates. The relationship between muscle ATP turnover rate and free ADP concentration was complex; again, a kinetic order of 1 was not observed. In contrast to the gastrocnemius, the soleus muscle sustained much smaller changes in the concentrations of these crucial metabolites during rest-work-recovery transitions. Unlike the situation in most other muscles rich in fast-twitch fibers characterized by lactate-associated acidosis during muscle work, the intracellular pH in gastrocnemius of Sherpas was stable through these protocols, which is consistent with the low lactate production (i.e., with the lactate paradox) observed in indigenous highlanders.

Adenosine Diphosphate↗

PubMed1997

Clinical antecedents of neurologic and audiologic abnormalities in survivors of neonatal extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation is an effective rescue treatment for severe cardiorespiratory failure in term or near term neonates, although cerebral palsy, mental retardation, and sensorineural hearing loss are observed in 10 to 20% of survivors. The objective of the present study was to identify potential risk factors that may explain the neurologic and audiologic sequelae noted in 19% of 181 survivors of neonatal extracorporeal membrane oxygenation from our hospital. Our results suggest the following findings in survivors of severe cardiorespiratory failure treated with neonatal extracorporeal membrane oxygenation: (1) hypotension or the need for cardiopulmonary resuscitation before extracorporeal membrane oxygenation significantly increases the risk of spastic cerebral palsy, (2) profound hypocarbia before extracorporeal membrane oxygenation is associated with a significantly increased risk of hearing loss, (3) mental retardation in the absence of spastic cerebral palsy is unexplained except when due to abnormal fetal brain development, and (4) hypoxemia in the absence of hypotension does not increase the risk of neurologic or audiologic sequelae.

Brain↗

PubMed1996

31P magnetic resonance spectroscopy of the Sherpa heart: a phosphocreatine/adenosine triphosphate signature of metabolic defense against hypobaric hypoxia.

Of all humans thus far studied, Sherpas are considered by many high-altitude biomedical scientists as most exquisitely adapted for life under continuous hypobaric hypoxia. However, little is known about how the heart is protected in hypoxia. Hypoxia defense mechanisms in the Sherpa heart were explored by in vivo, noninvasive 31P magnetic resonance spectroscopy. Six Sherpas were examined under two experimental conditions [normoxic (21% FiO2) and hypoxic (11% FiO2) and in two adaptational states--the acclimated state (on arrival at low-altitude study sites) and the deacclimating state (4 weeks of ongoing exposure to low altitude). Four lowland subjects were used for comparison. We found that the concentration ratios of phosphocreatine (PCr)/adenosine triphosphate (ATP) were maintained at steady-state normoxic values (0.96, SEM = 0.22) that were about half those found in normoxic lowlanders (1.76, SEM = 0.03) monitored the same way at the same time. These differences in heart energetic status between Sherpas and lowlanders compared under normoxic conditions remained highly significant (P < 0.02) even after 4 weeks of deacclimation at low altitudes. In Sherpas under acute hypoxia, the heart rate increased by 20 beats per min from resting values of about 70 beats per min, and the percent saturation of hemoglobin decreased to about 75%. However, these perturbations did not alter the PCr/ATP concentration ratios, which remained at about 50% of the values expected in healthy lowlanders. Because the creatine phosphokinase reaction functions close to equilibrium, these steady-state PCr/ATP ratios presumably coincided with about 3-fold higher free adenosine diphosphate (ADP) concentrations. Higher ADP concentrations (i.e., lower [PCr]/[ATP] ratios) were interpreted to correlate with the Km values for ADP-requiring kinases of glycolysis and to reflect elevated carbohydrate contributions to heart energy needs. This metabolic organization is postulated as advantageous in hypobaria because the ATP yield per O2 molecule is 25-60% higher with glucose than with free fatty acids (the usual fuels utilized in the human heart in postfasting conditions).

Acclimatization↗

PubMed1996

The role of infant factors in postnatal depression and mother-infant interactions.

A large group of infants of primiparous women who were at high risk fo r postnatal depression (N=188) and a smaller group of those at low risk (N=43) were assessed in the neonatal period using the Neonatal Behavioural Assessment Scale. Poor motor scores and high irritability were strongly predictive of the onset of maternal depression by eight weeks postpartum. These effects obtained after taking account of both maternal mood in the neonatal period and maternal perceptions of infant temperament. Poor motor scores and high levels of infant irritability in the neonatal period also predicted less optimal infant behaviour in face-to-face interactions with the mother at two months postpartum. Neonatal behaviour did not predict the persistence of depression, nor did it predict the quality of maternal behaviour in interaction with the infant.

Adult↗