Parental preferences for neonatal resuscitation research consent: a pilot study.

OBJECTIVE: Obtaining informed consent for resuscitation research, especially in the newborn, is problematic. This study aimed to evaluate parental preferences for hypothetical consent procedures in neonatal resuscitation research. DESIGN: Mail-out survey questionnaire. SETTING/ PARTICIPANTS: Randomly selected parents who had received obstetrical or neonatal care at a tertiary perinatal centre. MAIN OUTCOME MEASURES: Parental levels of comfort (Likert-type scale 1-6) regarding different methods of obtaining consent in hypothetical resuscitation research scenarios. RESULTS: The response rate was 34%. The respondents were a group of highly educated women with a higher family income than would be expected in the general population. In terms of results, parents valued the impact the research would have on their baby and the importance of a positive interaction with the physicians conducting the research study. Parents felt most comfortable with prospective consent in the setting of prenatal classes or prenatal visits with a physician, but they were somewhat uncomfortable with prospective consent upon admission to hospital after labour had begun. Parents were uncomfortable with waived consent, deferred consent, and opting out, no matter when during the pregnancy consent was requested. CONCLUSION: This pilot study reports parental preferences for prenatal information and consent for such research trials of neonatal resuscitation. A low response rate and potentially skewed demographics of the respondents prevent generalisability of this result. Interview studies should be performed to better determine parental preferences for informed consent in a more representative population.

Protein kinase C overactivity impairs prefrontal cortical regulation of working memory.

The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.

Mechanics of solid tissue invasion by the mammalian pathogen Pythium insidiosum.

The relative significance of mechanical penetration versus the action of substrate-degrading enzymes during solid tissue invasion has not been established for any fungal disease. Pythium insidiosum is an oomycete fungus (or stramenopile) that causes a rare, but potentially lethal infection in humans and other mammalian hosts. Experiments with miniature strain gauges showed that single hyphal apices of this pathogen exert forces of up to 6.9 microN, corresponding to maximum pressures of 0.3 microN microm(-2) or MPa. Samples of cutaneous and subcutaneous tissue from fresh human cadavers displayed a mean strength (resistance to needle puncture) of 24 microN microm(-2), and a mean pressure of 30 microN microm(-2) was necessary to penetrate skin strips from slaughtered horses. These experiments demonstrate that P. insidiosum does not exert sufficient pressure to penetrate undamaged skin by mechanics alone, but must effect a decisive reduction in tissue strength by proteinase secretion.

Intracellular freezing, viability, and composition of fat body cells from freeze-intolerant larvae of Sarcophaga crassipalpis.

Although it is often assumed that survival of freezing requires that ice formation must be restricted to extracellular compartments, fat body cells from freeze-tolerant larvae of the gall fly, Eurosta solidaginis (Diptera, Tephritidae) survive intracellular freezing. Furthermore, these cells are highly susceptible to inoculative freezing by external ice, undergo extensive lipid coalescence upon thawing, and survive freezing better when glycerol is added to the suspension medium. To determine whether these traits are required for intracellular freeze tolerance or whether they are incidental and possessed by fat body cells in general, we investigated the capacity of fat body cells from nondiapause-destined and diapause-destined (i.e., cold-hardy) larvae of the freeze-intolerant flesh fly Sarcophaga crassipalpis (Diptera, Sarcophagidae) to survive intracellular freezing. Fat body cells from both types of larvae were highly susceptible to inoculative freezing; all cells froze between -3.7 to -6.2 degrees C. The highest rates for survival of intracellular freezing occurred at -5 degrees C. The addition of glycerol to the media markedly increased survival rates. Upon thawing, the fat body cells showed little or no lipid coalescence. Fat body cells from E. solidaginis had a water content of only 35% compared to cells from S. crassipalpis larvae that had 52-55%; cells with less water may be less likely to be damaged by mechanical forces during intracellular freezing.

Inappropriately high plasma insulin levels in suspected perinatal asphyxia.

The aim of this study was to determine differences in levels of the major hormones responsible for glucose homeostasis (insulin and glucagon) in babies with acute neonatal encephalopathy secondary to perinatal asphyxia and to correlate these with outcome. In a prospective observational study, plasma insulin, C-peptide, glucagon and serum glucose levels were determined using standard techniques at specified times in term babies with a diagnosis on admission of perinatal asphyxia or acute neonatal encephalopathy. The setting comprised two university-affiliated, regional, tertiary level neonatal intensive care units. Thirty-one babies with a diagnosis of perinatal asphyxia or acute neonatal encephalopathy were entered into the study over 15 months and neurodevelopmental outcomes at 18 months of age for 28 babies were available for analysis. Babies with a poor neurodevelopmental outcome had significantly higher insulin and C-peptide levels than those who had a good outcome. Glucose delivery, serum glucose and glucagon levels did not differ significantly between the babies with a poor outcome and those with a good outcome. In conclusion, babies with significant foetal or neonatal asphyxia frequently have inappropriately high plasma insulin levels. This, either alone or in combination with other hormonal disturbances, may lead to the hypoglycaemia often associated with severe asphyxia and may predict a poor outcome.

Plasma thyroid hormones in premature infants: effect of gestational age and antenatal thyrotropin-releasing hormone treatment. TRH Collaborative Trial Participants.

Thyroid hormones are important for both perinatal adaptation and long-term psychomotor development; however, there is limited information on the effects of extreme prematurity and antenatal TSH-releasing hormone (TRH) treatment on pituitary-thyroid function. In this study we assayed plasma triiodothyronine (T3) and TSH in infants who were part of a collaborative trial of antenatal maternal TRH therapy. Within the control population (n = 166), infants of 24-28-wk and 28-32-wk gestational age had comparable levels of T3 (0.94 and 1.06 nmol/L, respectively) and TSH (5.7 and 7.2 mU/L) at birth, but the increases at 2 h and subsequent T3 levels were less in the 24-28 wk versus 28-32-wk gestation infants. In the TRH-treated group (n = 131), T3 was lower in the first day for infants delivered 7-72 h after antenatal TRH compared with control infants. TSH at birth was approximately 3.5-fold greater for infants delivered at 0-6 h after the last TRH dose compared with the control group and was suppressed in infants delivering at 7-36 h. T3 and TSH levels were not different between control and TRH-treated groups at 3-28 d of age. In TRH stimulation tests on d 28, control and TRH-treated groups had similar peak levels of TSH and incidence of exaggerated response (TSH > or = 35 mU/L). We conclude that extremely premature infants have a reduced postnatal surge in TSH and T3 and maintain lower T3 concentrations, probably reflecting tertiary hypothyroidism. The stimulatory and suppressive effects of antenatal TRH treatment observed at birth are transient and do not affect pituitary-thyroid responsiveness at 28 d of age.

Antenatal thyrotropin-releasing hormone to prevent lung disease in preterm infants. North American Thyrotropin-Releasing Hormone Study Group.

BACKGROUND: Pulmonary disease is common in preterm infants, despite antenatal glucocorticoid therapy. The addition of antenatal thyrotropin-releasing hormone therapy has been reported to decrease pulmonary morbidity in these infants. METHODS: We enrolled 996 women at 13 North American centers who were in preterm labor at <30 weeks' gestation in a double-blind, placebo-controlled, randomized trial of antenatal thyrotropin-releasing hormone, given intravenously in four doses of 400 microg each at eight-hour intervals. The primary outcome was chronic lung disease or death of the infant on or before the 28th day after delivery, and secondary outcomes were respiratory distress syndrome and chronic lung disease or death at 36 weeks' postmenstrual age. Complete data were available for 981 women and their 1134 live-born infants. The 769 infants born at < or = 32 weeks' gestation were defined as the group at risk. RESULTS: There were no significant differences between the at-risk treatment and placebo groups in mean (+/-SD) birth weight (1109+/-354 vs. 1097+/-355 g), gestational age (27.9+/-2.1 vs. 27.9+/-2.1 weeks), sex, or race. The frequencies of respiratory distress syndrome (66 percent vs. 65 percent), death at 28 days (11 percent vs. 11 percent), chronic lung disease or death at 28 days (45 percent vs. 42 percent) and at 36 weeks (32 percent vs. 34 percent), and other neonatal complications as well as the severity of lung disease were not significantly different in the at-risk treatment and placebo groups. Similarly, there were no differences in outcome between the treatment and placebo groups for the infants born at >32 weeks' gestation. CONCLUSIONS: In preterm infants at risk for lung disease, antenatal administration of thyrotropin-releasing hormone and glucocorticoid is no more beneficial than glucocorticoid alone.

Grief, parenting, and schizophrenia.

It is argued that a child with schizophrenia represents an ongoing source of loss and grief for parents. The study aimed to (a) validate the presence of grief in mothers and fathers of children with schizophrenia, and (b)explore whether the hours of parental contact with the child influences the strength of grief reactions. The mean age (62 years) of the 16 mother-father dyads constituted an investigation of older parents, for 43% of whom the duration of diagnosed schizophrenia was over 10 years. Grief was conceptualised as a cognitive, behavioural, and emotional reaction to loss, and was operationalized by measuring current intrusive thoughts and avoidance behaviours, as well as emotional distress over reminders of time of diagnosis. As hypothesised, mothers and fathers were grieving in relation to their child's psychiatric illness. No differences between mothers and fathers in intrusive thinking, avoidance behaviours, and distress related to recall of diagnosis were detected. With the exception of intrusive thoughts, number of contact hours with the child was not an intervening variable of mothers' and fathers' grieving.

Temperature and viscosity dependence of the electron-transfer reaction between plastocyanin and cytochrome c labeled with a ruthenium(II) bipyridine complex.

The temperature and viscosity dependence of the photo-induced electron-transfer reaction between plastocyanin and cytochrome c labeled at Lys13 with Ru(4,4'-dicarboxybipyridine)(bipyridine)(2+)2 have been investigated. In these studies, a short pulse of 450 nm light was used to excite the ruthenium complex which was oxidatively quenched by the iron center of cytochrome c. The resulting Fe(II) cytochrome c was then rapidly reoxidized by plastocyanin. The reactions were investigated over a temperature range of 3.5 to 37 degrees C under low ionic strength conditions such that protein/protein complex formation was favored. The enthalpy of activation was 7 kcal mol-1 and the entropy of activation was -20 cal mol-1 K-1. Increasing the viscosity by the addition of sucrose up to 70% resulted in a 4-fold decrease in the rate constant for electron transfer. The overall results suggest a rate-limiting step that involves either dissociation of the dominant protein/protein complex or surface diffusion of the associated proteins.

In vivo chronoamperometric measurements of the clearance of exogenously applied serotonin in the rat dentate gyrus.

The present study evaluated high-speed chronoamperometry as a method for measuring the clearance of serotonin (5-HT) from extracellular space in vivo. Male Sprague-Dawley rats were anaesthetized and a Nafion-coated, carbon fiber electrode, attached to a multibarrel pipette, was lowered into the subgranular layer of the dentate gyrus, a region which receives dense serotonergic innervation, or the corpus callosum, a fiber tract relatively devoid of the 5-HT transporter (SERT). Serotonin, pressure ejected into these regions, produced replicable electrochemical signals. The amplitude and time course of the signals were significantly prolonged in the corpus callosum compared to the dentate gyrus. Similarly, signals produced by locally applied 5-HT in the dentate gyrus of rats following destruction of hippocampal serotonergic innervation with 5,7-dihydroxytryptamine (5,7-DHT), were significantly enhanced compared to those observed in control animals. The time course of the 5-HT signal was significantly prolonged by local application of the selective 5-HT reuptake inhibitor, fluvoxamine, into the dentate gyrus. By contrast, fluvoxamine did not modify the clearance of 5-HT when locally applied into the dentate gyrus of 5,7-DHT lesioned rats or into the corpus callosum of intact rats. Taken together, these data demonstrate that in intact rats, the SERT contributes to the clearance of exogenously applied 5-HT from the extracellular space. Under the experimental conditions used in this study, high-speed chronoamperometry proved to be a reliable method for directly measuring extracellular 5-HT and appears to be a valuable tool for the study of 5-HT clearance by the SERT in vivo.

A curriculum for teaching clinical ethics in neonatal-perinatal medicine.

Ethical thought plays a role in clinical decision-making, especially in fields such as neonatal-perinatal medicine. There is limited information, however, on the best way to teach ethics to postgraduate medical trainees in this subspeciality. This article describes the development, implementation, and evolution of a structured curriculum in ethics for a program in neonatal-perinatal medicine. The curriculum is facilitated by a specialist in ethics and based on hypothetical case scenarios, which are discussed using a framework that highlights the ethical values promoted or neglected in each decision option. Formal evaluation of the program has been impossible, but informal reviews indicate that there is a high degree of satisfaction.

Characterisation of the beta adrenergic response cascade in fetal guinea pig lung.

BACKGROUND: Suitable models for the study of lung development are needed. The suitability of the guinea pig for studying the role of the beta adrenergic response cascade in fetal lung development has been evaluated. METHODS: Radioligand binding assays with iodine-125 labelled iodopindolol were performed to identify and characterise the beta adrenergic receptors. To demonstrate that these receptors were functional, isoprenaline and forskolin stimulated generation of cyclic AMP (cAMP) in the lung tissue was quantitated by radioimmunoassay. RESULTS: The concentration of beta receptors increased with gestational age from 23 fmol/mg at 35 days to 140 fmol/mg at 64 days. Competition binding studies were consistent with a predominance of beta 2 receptors. The ability of isoprenaline to stimulate cAMP generation was greater during the saccular phase than during the canalicular phase of lung development. Incorporation of tritium labelled choline into phosphatidylcholine increased significantly between the canalicular and saccular phases. CONCLUSIONS: The beta adrenergic response cascade in fetal guinea pig lung exhibits similar characteristics to those previously described in fetal human lung and is therefore a good model in which to study the effects of beta agonists on fetal lung development.

Self-localization in US of appendicitis: an addition to graded compression.

Graded-compression ultrasound (US) of the right lower quadrant (RLQ) has been a valuable addition to the diagnostic evaluation of acute appendicitis. In an effort to expedite the sonographic evaluation and improve diagnostic accuracy, a method of self-localization was added to the standard graded-compression examination. A total of 236 patients with signs of appendicitis were studied. Eighty-five percent (121 of 142) of the patients with proved appendicitis were able to decisively self-localize their pain. Of the patients without appendicitis who still had significant disease in the RLQ, 88% (29 of 33) were able to self-localize their pain, with an accuracy rate of 86% for significant disease. Among patients without significant disease, only 15% (nine of 61) self-localized their pain. This "sonographic self-localization sign" reduced the time of the examination and was a valuable addition to standard graded-compression US of the appendix.

Community health nursing in rural and frontier counties.

This article discusses the nature and problems of community health nursing practice in large, sparsely populated rural areas. Data were obtained from more than 30 rural community health nurses practicing in a variety of settings. Salient characteristics and a beginning descriptive theory of rural community health nursing practice are presented.

Hill-Sachs lesion: comparison of detection with MR imaging, radiography, and arthroscopy.

Magnetic resonance (MR) imaging has proved to be a valuable method for documenting Hill-Sachs lesions. The authors retrospectively analyzed the diagnostic interpretations at plain film radiography, arthroscopy, and MR imaging in 76 patients. The analysis revealed that neither radiography nor arthroscopy displayed the lesion with sufficient accuracy to represent a true standard of reference for the evaluation of MR imaging in the diagnosis of the Hill-Sachs lesion. The data from the diagnostic interpretations were analyzed in three ways, each of which revealed that findings at MR imaging were more helpful than findings at radiography and/or arthroscopy in the diagnosis of the Hill-Sachs lesion. When the agreement of findings in two or three methods was used to assign a final diagnosis, MR imaging resulted in sensitivity of 97%, specificity of 91%, and accuracy of 94% in the detection of Hill-Sachs lesions.

Insulin inhibits beta-adrenergic responses in fetal rabbit lung in explant culture.

Infants of diabetic mothers are at increased risk of a number of problems at birth. Among these problems are increased risks of respiratory distress syndrome and transient tachypnea of the newborn. Because surfactant synthesis, surfactant secretion, and lung fluid resorption are all mediated in part by beta-adrenergic responses, we asked if excess insulin interferes with the beta-adrenergic response cascade in fetal lung. Lungs from fetal rabbits (26 day) were grown in explant culture in hormone-supplemented culture medium. The explants were harvested after 48 h exposure to hormones and processed for determination of beta-adrenergic receptor concentration, guanine nucleotide regulatory proteins (Gs, Gi), beta-agonist stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation, cAMP-dependent phosphodiesterase activity, and choline incorporation into phosphatidylcholine. Although insulin did not change the concentration of beta-adrenergic receptors, it decreased the ability of isoproterenol to stimulate cAMP generation. Increase in stimulation over basal was similar in explants treated with dexamethasone and dexamethasone plus insulin, but absolute levels of isoproterenol-stimulated cAMP were less in the explants treated with dexamethasone plus insulin. We speculate that insulin inhibition of cAMP generation may be important in the pathogenesis of the respiratory problems of infants of diabetic mothers.

Glomerular alterations in idiopathic haematuria--ultrastructural and morphometric analysis.

Re-evaluation of kidney biopsies has been done along with morphometric analysis of glomerular basement membrane thickness (G.B.M.) in 41 cases of idiopathic haematuria, in whom the initial routine light, immunofluorescent and electron microscopic examination had not shown any significant alterations. Extreme attenuation of G.B.M. (mean thickness of 2581 +/- 488 A) had been found in thirty one patients in contrast to mean GBM thickness of 4295 +/- 470 A found in control group. Absence of any history of familial haematuria in these patients distinguished them from hereditary nephropathies and hence categorized under the term thin basement membrane nephropathy. Follow up of these patients for upto 8 years had shown persistence of symptoms without further deterioration of renal function as well as morphology.