Reproducibility of head-up tilt-table testing in pediatric patients with neurocardiogenic syncope.

The aim of this study is to assess the reproducibility of a head-up tilt-table test protocol so it may be used to more accurately evaluate the effectiveness of a treatment protocol. Children between the ages of 10 and 18 years presenting to the cardiology department at Children's Hospital of Wisconsin with a diagnosis of neurocardiogenic syncope were eligible for the study. The patients were tilted to 70 degrees for 30 minutes or until a positive test occurred. Patients with a positive test were retilted using the same protocol. Parameters measured included heart rate, blood pressure, and the presence or absence of syncope or presyncope. Twenty-two patients were enrolled in the study. Seventeen patients had a positive test on first tilt. Fifteen had a positive tilt test on the second tilt. There were no significant differences between the two tilts with regard to mean differences of baseline heart rate, systolic blood pressure, or mean arterial pressure. There were no significant differences between the two tilts with regard to mean differences in time until symptoms, heart rate, systolic blood pressure, or mean arterial blood pressure at time of symptoms. This study shows that the head-up tilt-table test protocol used is reproducible in adolescents with the diagnosis of neurocardiogenic syncope.

Pitfalls of adverse event reporting in paediatric cardiac intensive care.

AIMS: To evaluate the pitfalls of incident reporting in a complex medical environment. METHODS: Retrospective review of 211 incident reports in a paediatric cardiac intensive care unit (CICU). Two adverse event reporting databases were compared: database A (DA), the hospital's official reporting system, is non-anonymous and reports are predominantly made by nurses; database B (DB) is anonymous and reports are submitted by a CICU consultant who collects data from daily ward rounds. Both databases classify adverse events into incident type (drug errors, ventilation, cannulae/indwelling lines, chest drains, blood transfusion, equipment, operational) and severity (0 = no, 1 = minor, 2 = major, 3 = life threatening consequences). RESULTS: Between 1 April 1998 and 31 July 2001 there were 211 adverse events involving 178 patients (11.87%), among 1500 patients admitted to CICU. A total of 112 incidents were reported in DA, 143 in DB, and 44 in both. In isolation, both databases gave an unrepresentative picture of the true frequency and severity of adverse events. Under-reporting was especially notable for less severe events (grade 0, or near misses) CONCLUSION: Incident reporting in the medical field is highly variable, and is heavily influenced by profession of the reporters as well as anonymity. When adverse event reporting is based predominantly on the observations of a single professional group, the data are grossly inaccurate.

Synchronous bilateral VATS decortication for paediatric bilateral empyema.

Bilateral empyema is a rare condition in children. In the current era of minimally invasive surgical treatment, our experience with two cases suggests that video thoracoscopic drainage and decortication for children with bilateral empyema is safe, effective, and potentially less expensive.

Management of pulmonary venous obstruction after correction of TAPVC: risk factors for adverse outcome.

OBJECTIVE: Recurrent pulmonary venous obstruction (PVO) occurs in 0-18% of infants undergoing correction of total anomalous pulmonary venous connection (TAPVC). Limited published data suggest that PVO usually develops within 6 months of primary repair, and that outcomes of reoperations are poor. This study aimed to review our experience of reoperations for PVO post-TAPVC repair and to identify risk factors for adverse outcome. METHODS: Twenty patients underwent reoperation for PVO between 1982 and 2002. Clinical data were reviewed. TAPVC was mostly infracardiac (11 patients). TAPVC was obstructed in nine patients. PVO developed early (<6 months) in seven patients, and late in 13 (>6 months). Time of presentation was unrelated to type of PVO (anastomotic vs. ostial). Repair was accomplished using various techniques (anastomotic enlargement with native atrial tissue, enlargement with pericardium, free or in situ, or other prosthetic material). Follow-up ranged from 1 month to 15 years (average 44 months). RESULTS: Thirteen patients received one reoperation, while seven had multiple reoperations. In 13 patients, PVO was defined as new onset (no obstruction post-TAPVC repair), and in seven patients as residual (minimal obstructive changes post-TAPVC repair that progressed to PVO). Ten patients presented with anastomotic PVO, six with anastomotic and ostial PVO (involving the PVs), three with ostial PVO, and one with coronary sinus-left atrial junction stenosis. Mortality was 25% (5/20). Six of the ten patients with anastomotic PVO underwent one reoperation (2/6 died); the other four developed ostial PVO after reoperation, requiring multiple procedures (2/4 died). Mode of presentation (new onset vs. residual), site of obstruction (anastomotic vs. ostial), preoperative RV pressure (<0.8 vs. >0.8 systemic), number of reoperations (single vs. multiple), residual obstruction (presence or absence), and operative approach (Gore-tex or not) did not seem to affect outcomes. Risk factors for death were early presentation (<6 months) and persistence of pulmonary hypertension after reoperation; early presentation was also a risk factor for multiple reoperations. CONCLUSIONS: Our findings support the conclusion that early presentation and postoperative pulmonary hypertension have the greatest adverse impact on outcome. Of these, failure to achieve a low-pressure pulmonary vascular system seems to be the variable that most strongly prevents survival. In our series, neither ostial PVO nor multiple re-interventions significantly increased surgical risk. The negative impact of postoperative residual obstruction on outcome was not striking. However, an aggressive surgical approach to this disease is still warranted. Although the role of each technique in obtaining long-lasting relief of PVO remains to be established, the use of artificial material seems unwise.

Traumatic disruption of the ascending aorta in a child after heart transplant.

We report a traumatic disruption of the ascending aorta in an 8-year-old boy who had undergone orthotopic cardiac transplant at 6.5 years of age for congenital heart block and dilated cardiomyopathy. At presentation his aortic injury was not immediately recognized, but persistence in identifying and confirming a suspicious aortic rupture was lifesaving.

Nitric oxide regulates endothelium-dependent vasodilator responses in rabbit hindquarters vascular bed in vivo.

The objective of this study was to determine whether nitric oxide (NO) could function as a negative feedback modulator of endothelium-dependent vasodilation in vivo. To this end, the influence of exogenous NO on vasodilator responses in the rabbit hindquarters vascular bed was determined. Previous in vitro studies have demonstrated that NO inhibits both neuronal NO synthase from rat cerebellum as well as NO synthase derived from bovine aortic endothelial cells. The present study was conducted in the rabbit hindquarters vascular bed under conditions of constant blood flow so that changes in pressure directly reflected changes in vascular resistance. Under these in vivo conditions, the NO donor agent S-nitroso-N-acetylpenicillamine (SNAP) reversibly attenuated responses to the endothelium-dependent vasodilators, acetylcholine and bradykinin. In contrast, SNAP did not influence the endothelium-independent vasodilator response to SNAP itself or to 8-bromoguanosine 3',5'-cyclic monophosphate. These observations indicate clearly that NO interferes with endothelium-dependent vasodilator action and support the view that endogenous NO may actually play a physiological role in regulating vascular tone.

Effects of prenatal ethanol exposure on the hippocampal neurochemistry of albino rats at 90 days of postnatal age.

OBJECTIVE: Our purpose was to test the hypothesis that prenatal ethanol exposure alters the hippocampal muscarinic cholinergic neurochemistry of albino rats. STUDY DESIGN: Ethanol was administered in a liquid diet to pregnant albino Sprague-Dawley rats. Liquid diet control animals received the same diet in which ethanol was replaced by an isocaloric amount of maltose-dextrin. Chow-fed control animals were fed laboratory chow as desired. Progeny were killed at 90 days of age, and their hippocampi were analyzed for muscarinic cholinergic receptors by use of tritiated quinuclidinyl benzilate. RESULTS: Prenatal ethanol exposure produced a statistically significant decrease in the number of muscarinic receptors in males. Similar trends were noted in females, but the results were not statistically significant. CONCLUSION: Prenatal ethanol treatment caused long-lasting alterations in the muscarinic cholinergic receptors of the hippocampus in male rats.

Calcium channel involvement in GABAB receptor-mediated inhibition of GABA release in area CA1 of the rat hippocampus.

1. Experiments were performed in rat hippocampal slices to examine the nature of GABAergic inhibition of inhibitory synaptic transmission. In these experiments the effects of the gamma-aminobutyric acid-B (GABAB) receptor agonist, baclofen, and of subtype-selective calcium channel blockers were tested with the use of intracellular recordings of evoked inhibitory postsynaptic potentials (IPSPs) and whole cell recordings of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs). 2. Baclofen inhibited evoked and spontaneous (action-potential-dependent) monosynaptic GABAA-mediated IPSPs and IPSCs but had no effect on the frequency of tetrodotoxin-resistant (action-potential-independent) miniature IPSCs recorded in CA1 pyramidal neurons. 3. Depolarizing GABAergic synaptic terminals by raising the extracellular potassium concentration caused an increase in action-potential-independent miniature IPSC frequency that could be inhibited by either baclofen or cadmium, a blocker of voltage-dependent calcium channels. In addition, under these depolarizing conditions, cadmium occluded the baclofen inhibition of miniature IPSCs. These data suggest that baclofen reduces only depolarization-induced, not quantal, GABA release and that it does so by decreasing presynaptic voltage-dependent calcium influx. 4. Experiments with subtype-selective calcium channel blockers demonstrate that the presynaptic action of baclofen was mediated through both omega-conotoxin-GVIA-sensitive and omega-agatoxin-IVA-sensitive, but not dihydropyridine-sensitive calcium channels.

Role of nitric oxide in the relationship of pancreatic blood flow and exocrine secretion in cats.

BACKGROUND/AIMS: Recent studies have suggested that, in the gastrointestinal tract, nitric oxide is an important mediator of alterations in blood flow and, in some organs, a second messenger involved in secretion. This study examined the role of NO in changes in pancreatic blood flow associated with basal and stimulated pancreatic exocrine secretion. METHODS: In anesthetized cats, we determined the effects of the NO synthase inhibitor NG-monomethyl-L-arginine (10 mg/kg) and the NO donor sodium nitroprusside (10 micrograms.kg-1.min-1) on pancreatic secretion and blood flow (hydrogen gas clearance). RESULTS: NG-monomethyl-L-arginine had no effect on the increase in blood flow associated with secretin stimulation (271 +/- 52 vs. 290 +/- 50 mL.min-1.100 g-1) but reduced that associated with cholecystokinin stimulation (189 +/- 17 vs. 53 +/- 15 mL.min-1.100 g-1; P < 0.001). In contrast, NG-monomethyl-L-arginine significantly reduced both secretin- and cholecystokinin-stimulated secretion. Sodium nitroprusside had no effect on basal blood flow but significantly increased secretion. CONCLUSIONS: NO has a selective role in mediating changes in pancreatic perfusion and secretion. It seems to be important in stimulus-secretion coupling with both secretin and cholecystokinin but is only responsible for the accompanying increase in pancreatic blood flow with cholecystokinin.

Functional evidence for different endothelin receptors in the lung.

The present study was undertaken to compare and contrast the characteristics of the pulmonary and systemic vascular responses to endothelin (ET) isoforms in the intact spontaneously breathing cat under conditions of constant pulmonary blood flow and left atrial pressure. When pulmonary vasomotor tone (PVT) was actively increased by intralobar infusion of U-46619, intralobar arterial bolus injections of 1 microgram ET-1, 1 microgram ET-2, or 3 micrograms ET-3 markedly decreased lobar arterial pressure, systemic arterial pressure, and systemic vascular resistance. After seven repeated injections of ET-1 or ET-2 to separate groups of cats, pulmonary and systemic responses were largely reversed from vasodilation to vasoconstriction. In contrast, the pulmonary vasodilator response to ET-3 remained intact after multiple ET-3 injections, whereas its systemic vasodilator response was lost. Repeated intralobar arterial bolus injections of ET-1, ET-2, or ET-3 also caused the loss of pulmonary vasodilation to subsequent doses of ET-1, ET-2, or sarafotoxin 6b but not to ET-3. The present data suggest that the pulmonary and systemic vasodilator responses to ET-1 and ET-2 undergo tachyphylaxis and cross-tachyphylaxis. In contrast, the pulmonary vasodilator response to ET-3, unlike its systemic vasodilator response, is resistant to tachyphylaxis and cross-tachyphylaxis. The present data provide a functional correlate for the existence of at least two ET receptor subtypes, ETA-like and ETC-like receptors, in the adult pulmonary vascular bed.

Opioid inhibition of GABA release from presynaptic terminals of rat hippocampal interneurons.

Opiates and the opioid peptide enkephalin can cause indirect excitation of principal cortical neurons by reducing inhibitory synaptic transmission mediated by GABAergic interneurons. The mechanism by which opioids mediate these effects on interneurons is unknown, but enkephalin hyperpolarizes the somatic membrane potential of a variety of neurons in the brain, including hippocampal interneurons. We now report a new, more direct mechanism for the opioid-mediated reduction in synaptic inhibition. The enkephalin analog D-Ala2-Met5-enkephalinamide (DALA) decreases the frequency of miniature, action potential-independent, spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) without causing a change in their amplitude. Thus, we conclude that DALA inhibits the action potential-independent release of GABA through a direct action on interneuronal synaptic terminals. In contrast, DALA reduces the amplitude of action potential-evoked, GABA-mediated IPSCs, as well as decreases their frequency. This suggests that the opioid-mediated inhibition of non-action potential-dependent GABA release reveals a mechanism that contributes to reducing action potential-evoked GABA release, thereby decreasing synaptic inhibition.

MRI abnormalities in tardive dyskinesia.

Most investigators studying tardive dyskinesia (TD) hypothesize that the condition is due to a neurochemical abnormality of the striatum. Recently, numerous CT studies have been done to verify brain abnormalities in patients with TD; the findings have, however, been conflicting. The present study was designed to detect possible neuropathological abnormalities in the basal ganglia in a young sample of schizophrenic patients with TD as compared with schizophrenic patients without TD and normal controls. Magnetic resonance imaging (MRI) was used to measure the volumes of the caudate, putamen, globus pallidus, lateral ventricle, and intracranium. The volumes of the caudate nuclei of the patients with TD were significantly smaller than the volumes of the caudate nuclei of the patients without TD and normal controls. This abnormality in the caudate may be related to some previous conditions, which may prove a substrate that is necessary for TD to establish itself in association with neuroleptic use. Further studies are necessary to confirm our findings and to determine the pathophysiologic nature of these structural alterations and the role played by neuroleptics, whether primary or secondary.

Synaptic localization of adrenergic disinhibition in the rat hippocampus.

Norepinephrine is an endogenous neurotransmitter that reduces synaptic inhibition onto pyramidal neurons in the hippocampus by an action at an alpha-adrenergic receptor. The physiological mechanism of this disinhibition was previously not known, except that it occurred at a site presynaptic to the inhibited pyramidal cell. In this paper we present evidence that adrenergic disinhibition is restricted to the early phase of the evoked inhibitory postsynaptic potential in area CA1 of the hippocampus. The locus of disinhibition does not appear to reside in the interneuronal terminal, axon, or cell body. Instead, adrenergic agonists appear to reduce evoked synaptic inhibition by depressing excitatory synapses that activate the interneuron.

Pulmonary vasodilation to endothelin isopeptides in vivo is mediated by potassium channel activation.

The present study was undertaken to investigate the effects of endothelin (ET) isopeptides on the pulmonary vascular bed of the intact spontaneously breathing cat under conditions of constant pulmonary blood flow and left atrial pressure. When pulmonary vasomotor tone was actively increased by intralobar infusion of U-46619, intralobar bolus injections of ET-1 (1 microgram), ET-2 (1 microgram), and ET-3 (3 micrograms) produced marked reductions in pulmonary and systemic vascular resistances. The pulmonary vasodilator response to each ET isopeptide was not altered by atropine (1 mg/kg iv), indomethacin (2.5 mg/kg iv), and ICI 118551 (1 mg/kg iv) but was significantly diminished by glybenclamide (5 mg/kg iv). This dose of glybenclamide significantly diminished the decrease in lobar arterial and systemic arterial pressures in response to intralobar injection of pinacidil (30 and 100 micrograms) and cromakalim (10 and 30 micrograms), whereas pulmonary vasodilator responses to acetylcholine (0.03 and 0.1 microgram), prostaglandin I2 (0.1 and 0.3 microgram), and isoproterenol (0.03 and 0.1 microgram) were not altered. The systemic vasodilator response to each ET isopeptide was not changed by glybenclamide or by the other blocking agents studied. The present data comprise the first publication demonstrating that ET-1, ET-2, and ET-3 dilate the pulmonary vascular bed in vivo. The present data further suggest that the pulmonary vasodilator response to ET isopeptides depends, in part, on activation of potassium channels and is mediated differently from the systemic vasodilator response to these substances. Contrary to earlier work, the present data indicate the pulmonary vascular response to ET isopeptides does depend on the preexisting level of pulmonary vasomotor tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for distinct endothelin receptors in the pulmonary vascular bed in vivo.

The present study was undertaken to investigate the effects of endothelin (ET) isopeptides on the pulmonary vascular bed of the intact, spontaneously breathing cat under conditions of constant pulmonary blood flow and left atrial pressure. When pulmonary vasomotor tone was actively increased by intralobar infusion of U46619, intralobar bolus injections of ET-1 (1 micrograms), ET-2 (1 micrograms), and ET-3 (3 micrograms) produced marked reductions in pulmonary and systemic vascular resistances. The pulmonary vasodilator response to each ET isopeptide was not altered by atropine (1 mg/kg i.v.), indomethacin (2.5 mg/kg i.v.), or ICI 118551 (1 mg/kg i.v.), but was significantly inhibited by an intra-arterial (i.a.) infusion of glybenclamide at 5 mg/kg. This dose of glybenclamide significantly inhibited the decrease in lobar arterial and systemic arterial pressures in response to intralobar injection of pinacidil (30 and 100 micrograms), whereas the pulmonary vasodilator responses to acetylcholine (0.03 and 0.1 micrograms) and prostaglandin I2 (0.1 and 0.3 micrograms) were not altered. The systemic vasodilator response to each ET isopeptide was not changed by glybenclamide or by the other blocking agents studied. The present data demonstrate for the first time that ET-1, ET-2, and ET-3 dilate the pulmonary vascular bed in vivo. The present data suggest that the pulmonary vasodilator response to ET isopeptides depends, in part, on activation of potassium channels and is mediated differently from the systemic vasodilator response to these substances. Contrary to earlier work, the present data indicate the pulmonary vascular response to ET isopeptides depends on the pre-existing level of pulmonary vasomotor tone. Furthermore, the present data suggest that in the lung ET-1, ET-2, and ET-3 may serve as endogenous agonists for potassium channels, a newly described vasodilator mechanism in the pulmonary vascular bed of intact adult animals.

Developmental abnormalities of the corpus callosum in schizophrenia.

Magnetic resonance imaging was used to evaluate neuroanatomical and neuropathologic abnormalities in a consecutive series of 140 patients with schizophrenia for comparison with normal controls. Partial agenesis of the corpus callosum, a rare neurodevelopmental abnormality, was found in two patients, one of whom also had a callosal lipoma. Evidence is presented suggesting that this finding represents an increased prevalence of partial agenesis in schizophrenia. The corpus callosum develops embryologically in intimate relationship to the hippocampal formation, fornix, septum pellucidum, and cingulate gyrus. In individuals with callosal agenesis, abnormalities also occur in the development of these limbic structures. Recent neuropathologic studies have suggested the occurrence of abnormal neurogenesis in the hippocampal formation and in the cingulate gyrus in schizophrenic patients. An increased prevalence of callosal agenesis and its related limbic abnormalities would further support investigation into neurodevelopmental abnormalities of these anatomical regions in schizophrenia.

An allergist's view of atopic dermatitis.

Based on the disagreements about the role of atopy in the condition known as atopic dermatitis, it is not surprising that there have been divergent views concerning the appropriate treatment of the disease. A large population of physicians, including most dermatologists and some allergists, believe that the fundamental approach to a successful outcome of the dermatitis is to control the itching and to improve the chronic dryness of the skin. Following a completely different approach are physicians, including many allergists, who are convinced that atopic dermatitis usually involves an imbalance of, or an abnormality in, the immunologic system. For this group, one of the main features of treatment is to remove or avoid offending allergens. Because of the demonstrated pathogenic role of food allergy in the majority of patients with eczema, any child with chronic moderate or severe disease that requires daily medications should be considered for allergic evaluation of this disorder. Further studies still need to be performed concerning the role of environmental and food allergens and the early- and late-phase reactions in atopic dermatitis.