Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery: Diagnoses and Surgical Results in 12 Pediatric Patients

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital condition. It responds well to early diagnosis and treatment, but otherwise the prognosis is poor. We present our case series of 12 patients (mean age, 2 ± 2.58 yr; age range, 2 mo–8 yr), emphasizing the diagnostic process and discussing our surgical results. The diagnosis of ALCAPA should be suspected in infants who have dilated cardiomyopathy with electrocardiographic changes that suggest ischemia, and in older children who have isolated mitral regurgitation. When clinical suspicion is high, the results of 2-dimensional echocardiography combined with color-flow Doppler studies in expert hands can establish the diagnosis, thus avoiding angiography in critically ill infants. The treatment of choice in our patients was transfer and reimplantation of the left coronary artery onto the ascending aorta. There were 2 deaths: both were infants in extremis who underwent emergency surgery. An older child with severe ventricular dysfunction was given mechanical ventricular assistance and then heart transplantation. As of this report, all 10 survivors remained well and asymptomatic.     

Blood to brain sodium transport and interstitial fluid potassium concentration during early focal ischemia in the rat.

During partial ischemia, sodium and potassium ions exchange across the blood-brain barrier, resulting in a net increase in cations and brain edema. Since this exchange is likely mediated by specific transporters such as Na,K-ATPase in the capillary endothelium and because brain capillary Na,K-ATPase activity is stimulated by increased extracellular potassium in vitro, this study was designed to determine if the rate of blood to brain sodium transport is increased in ischemic tissue having an elevated interstitial fluid potassium concentration ([K]ISF) in vivo. Sprague-Dawley rats were studied between 2-3 h after occlusion of the right middle cerebral artery. To identify where cortical tissue with an elevated [K]ISF could be sampled for transport studies, the regional pattern of cerebral blood flow and [K]ISF was obtained in a group of 17 rats using hydrogen clearance and potassium-selective microelectrode techniques. We observed severely elevated [K]ISF (greater than 10 mM) when CBF was less than 20 ml 100 g-1 min-1 and mildly elevated levels at CBF between 20-45 ml 100 g-1 min-1. In a second group of seven rats, permeability-surface area products (PS products) for 22Na and [3H]alpha-aminoisobutyric acid ([3H]AIB) were determined in ischemic cortex with elevated [K]ISF and in nonischemic cortex. The PS products for AIB were similar in both tissues (2.2 +/- 0.7 and 2.1 +/- 0.4 microliters/g/min) while the PS products for sodium was significantly increased in the ischemic tissue (1.5 +/- 0.2 and 2.4 +/- 1.1 microliters/g/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Aqueductal stenosis as isolated localization involving the central nervous system in children affected by von Recklinghausen disease

The Authors report three cases of non tumoral aqueductal stenosis associated with von Recklinghausen disease in children. Moreover, 16 similar cases collected from the literature are illustrated. The clinical features are evaluated in light of literature's data. Among all 19 cases, the median age was 19 years (range 6-46 years) and 9 patients were under the age of 13 years. In this latter group, the most represented clinical symptoms were headache and gait disturbances. As regards the neuroradiological procedures, CT scan represented the best tool in the evaluation of the ventricular size. Our own three cases underwent to ventriculo-atrial shunt procedures, followed by clinical recovery (follow-up: 3 months-5 years). In conclusion it is felt that, among all the pathological events usually described in patients affected by neurofibromatosis, aqueductal stenosis seems to belong to the natural history of this disease.     

Unexpected effects of coffee consumption on liver enzymes

The effects of regular daily coffee consumption on liver enzymes were studied in a large number of subjects from the general population. In coffee drinkers, liver enzymes (gamma-glutamyl transferase, alkaine-amino transferase, and alkaline phosphatase) and serum bilirubin were lower than in non-coffee-drinking subjects or in those consuming less than 3 cups daily. The hypothesis proposed is that liver enzymes are a target for caffeine contained in coffee.     

New evidence for a gating action of norepinephrine in central neuronal circuits of mammalian brain

Many previous studies have examined the effects of norepinephrine (NE) on neuronal responsiveness to synaptic inputs and putative transmitter substances and have described differential depressant actions of NE on stimulus evoked versus spontaneous discharge such that the "signal to noise" ratio of threshold responses was increased. In the present studies, similar experimental strategies employing a combination of microiontophoresis, single unit recording and afferent pathway stimulation in intact anesthetized and brain tissue slice preparations have revealed noradrenergic "gating" actions whereby weak or subthreshold synaptic stimuli can evoke threshold neuronal responses in the presence of iontophoretically applied NE or following electrical stimulation of the locus coeruleus. Overall, these results suggest that potentially threshold excitatory and inhibitory synaptic inputs may normally arrive at central neurons but appear weak or absent except during behavioral conditions favoring the synaptic release of NE. As such, these findings provide evidence that signal to noise ratio may not be the only potential modulatory action expressed by NE in noradrenergic target circuits of the mammalian brain.     

Type A behavior and psychological characteristics of hypertensive patients undergoing antihypertensive treatment

The aim of this study was to evaluate the presence of "type A" behaviour and possible psychological distress in 373 hypertensive patients. One-hundred and ninety-five males, 56.2 +/- 6.2 years old and one-hundred and seventy-eight females, 57.1 +/- 6.2 years old, coming from the IPPPSH and still under double-blind treatment with or without a beta-blocker (oxprenolol 160 mg SR), were studied by means of the Jenkins Activity Survey form C and several tests from the Cognitive Behavioural Assessment Battery (CBA-2.0). Seventy-four point eight percent of the patients showed a "type A" pattern, and 25.5% were in the extreme predictive interval for coronary heart disease according to WCGS. "Type A" pattern was not influenced by variables such as age, sex, education, job or previous pharmacological treatment. The patients studied did not show any particular psychological distress at the psychometric evaluation. However, special social and cultural characteristics and different therapies influenced some symptoms, such as anxiety, depression and somatic lamentation. According to this study: "type A" behaviour seems to be a steady feature of the hypertensive patient; furthermore, it seems to be due to a "biological imprinting" which can be considered a cause of hypertension; psychological distress depends on a particular set of environmental stimuli. In the first case an accurate prevention is needed while, in the second case adequate pharmacological and/or psychological therapies are needed.     

Electrophysiological correlates of presynaptic alpha 2-receptor-mediated inhibition of norepinephrine release at locus coeruleus synapses in dentate gyrus

Despite an abundance of evidence that presynaptic alpha 2-adrenergic receptors mediate inhibitory control of the release of norepinephrine (NE) from the terminals of locus coeruleus (LC) neurons, few studies have demonstrated the physiological significance of this "autoreceptor"-mediated inhibition on NE-mediated synaptic activity within the mammalian brain. This question was addressed by examining the effects of systemic administration of alpha 2-adrenergic agonists and antagonists on the ability of LC stimulation to augment the population spike recorded in the dentate gyrus in response to activation of the perforant path (PP). Extracellular field potentials were recorded in the cell body and dendritic layer of dentate gyrus following single shocks of the entorhinal cortex in halothane-anesthetized rats. Stimulation of the ipsilateral LC 35 msec prior to PP activation produced a short-term enhancement of the population spike amplitude recorded in the cell layer but did not significantly alter dendritic potentials. The effects of LC stimulation were blocked by administration of the beta-adrenergic antagonist propranolol but not the alpha 2-antagonist idazoxan and were abolished by pretreatment of animals with the catecholamine neurotoxin 6-hydroxydopamine. Administration of clonidine reversibly abolished the enhancement produced by LC conditioning. The effect of clonidine was dose dependent and was blocked by administration of idazoxan, which restored the LC potentiative effect. Conditioning stimulation of LC noradrenergic axons in the dorsal bundle also potentiated the PP-evoked population spike, and this effect was equally sensitive to the depressant action of clonidine. In comparison, clonidine, in the range of dosages tested, did not significantly affect the potentials evoked in the dendritic or cell layer by presentations of unconditioned PP test stimuli. We interpret these data to provide evidence for a functional impairment of LC-mediated physiological action on postsynaptic target cells as a result of presynaptic alpha 2-autoreceptor-mediated feedback inhibition of NE release.     

Detection of expansion regions in Portuguese bipolar families

We have studied 24 families with multiple affected members with bipolar disorder to test the hypothesis that in those families clinically showing genetic anticipation [Macedo et al., 1999] we would find large repeat expansions. The families meeting inclusion criteria had a minimum of two affected members over two generations and showed marked anticipation both in terms of age of onset and disease severity. We used the repeat expansion detection (RED) method to test patients (n = 24) and controls from these families and unrelated controls (n = 53). We also genotyped patients and family members from two families with large expansions at the known expansion loci on chromosomes 13, 17, and 18. The RED method revealed a higher number of large expansions in patients compared with controls (t-test; P < 0.0055: Mann-Whitney U; P = 0.02). The patients with the largest expansions were typed at the specific loci on chromosomes 13, 17, and 18 and the chromosome 18 expansion locus segregated with disease in one family, and a second family showed segregation with the expansion located at the SCA8 locus on chromosome 13. Genetic anticipation had been analyzed in this cohort of families, with correction for potential ascertainment bias, possible proband effects, cohort effects, regression to the mean, gender effects, and maternal vs. paternal transmission. None of these potential confounds appeared to account for the observed anticipation. We also identified that the presence of large expansions in affected family members derives primarily from two families from the genetically isolated Azores population. One family shows segregation with the chromosome 18 locus, whereas the other family segregates with expansions at the SCA8 locus. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:854-857, 2000.