Caspr2-reactive antibody cloned from a mother of an ASD child mediates an ASD-like phenotype in mice.

Autism spectrum disorder (ASD) occurs in 1 in 68 births, preferentially affecting males. It encompasses a group of neurodevelopmental abnormalities characterized by impaired social interaction and communication, stereotypic behaviors and motor dysfunction. Although recent advances implicate maternal brain-reactive antibodies in a causative role in ASD, a definitive assessment of their pathogenic potential requires cloning of such antibodies. Here, we describe the isolation and characterization of monoclonal brain-reactive antibodies from blood of women with brain-reactive serology and a child with ASD. We further demonstrate that male but not female mice exposed in utero to the C6 monoclonal antibody, binding to contactin-associated protein-like 2 (Caspr2), display abnormal cortical development, decreased dendritic complexity of excitatory neurons and reduced numbers of inhibitory neurons in the hippocampus, as well as impairments in sociability, flexible learning and repetitive behavior. Anti-Caspr2 antibodies are frequent in women with brain-reactive serology and a child with ASD. Together these studies provide a methodology for obtaining monclonal brain-reactive antibodies from blood B cells, demonstrate that ASD can result from in utero exposure to maternal brain-reactive antibodies of single specificity and point toward the exciting possibility of prognostic and protective strategies.

Periodontal status in the Down's syndrome subjects living in central-eastern Italy: the effects of place of living.

AIM: The purpose of this study was to determine the influence of the place of living on periodontal status of 62 Down's syndrome (DS) subjects resident at home (DSH) or in specialized institutes (DSI) in central-eastern Italy. METHODS: The demographic characteristics of the subjects and the periodontal variables were evaluated according to their living conditions. Descriptive analyses were conducted by stratifying subjects into three age groups (0-13; 14-22; >23 years), using medians and 25th-75th percentiles to summarized data. Comparisons between DSH and DSI subjects were performed using Wilcoxon rank sum test. The effect of demographic and clinical variables on periodontal status was evaluated by means of quantile regression analysis. RESULTS: No significant differences resulted between DSH and DSI patients, when compared for gender, age and mental retardation. No significant differences were found in the periodontal variables for the subjects with 0-13 years, while DSI subjects between 14 and 22 years of age presented higher levels of plaque index, probing depth, clinical attachment loss and a lower number of surviving teeth compared to DSH subjects. When DSI and DSH groups ≥ 23 years of age were compared, no differences were observed in the periodontal conditions except for PI and the number of surviving teeth. Age, body mass index and severe mental retardation were found to be significant predictors of periodontal conditions. CONCLUSIONS: Institutionalization has a negative effect on surviving teeth number of Down's syndrome subjects. Furthermore, the home care seems to produce benefits on the periodontal conditions of DSH 14-22 years of age.

Asistencia ventricular mecánica como puente al trasplante en pacientes en shock cardiogénico: Experiencia preliminar en Chile con ABIOMED BVS 5000® / Ventricular assist device as a bridge to transplant in patients with cardiogenic shock: Report of four patients

Hospitalization and death due to heart failure and cardiogenic shock is frequent and currently is increasing among the adult population. Although cardiac transplantation is the most effective treatment in patients with end-stage heart failure, its availability is limited. While waiting for transplantation, some patients become refractory to treatment and deteriorate progressively. Secondary multi-organ damage could highly compromise the transplant success and also could contraindicate it. Mechanical ventricular assist devices allow reestablishing normal cardiac output and they have been used as a bridge to recovery and transplantation. We report four patients that underwent mechanical ventricular support using the ABIOMED BVS 5000® system as a bridge for transplantation. Two patients were connected to biventricular assistance; a third patient was connected to a left ventricular support and the fourth to a right ventricular support. Three were successfully transplanted and one died of refractory non-cardiogenic shock. There were no complications related to the support system, such as infection, hemorrhage or stroke. In our experience, the ABIOMED BVS 5000® was an effective strategy as a bridge to heart transplant in patients in cardiogenic shock.

Appendicitis masquerading as tumor: a case of two diagnoses.

Acute appendicitis remains one of the most difficult diagnoses to make in the Emergency Department. We present a puzzling and unusual case. A 47-year-old man had several hours of acute abdominal pain in the right upper quadrant, point tenderness in the right midquadrant on examination, and normal chemistries. Early appendicitis was suspected and a computed tomography (CT) scan of the abdomen was obtained. Appendicitis was not seen. What was evident was a retroperitoneal lipoma estimated to weigh 10 pounds. The general surgeon was consulted who believed that operation was necessary in light of the patient's continuing abdominal pain and the presence of the mass. Masses this large could cause pain from local compression of structures, or ischemia of the mass from outgrowing its blood supply. In surgery, a lipoma was observed that filled most of the retroperitoneum and displaced all the contents of the abdomen, including the cecum and its appendix. Also present was an acute appendicitis. On retrospective analysis of the CT scan, the appendicitis was evident but atypically located in the epigastrium. This case illustrates once again that the CT scan is a useful diagnostic adjunct for the diagnosis of new onset abdominal pain and specifically for appendicitis.

Phenotypic differentiation during migration of dopaminergic progenitor cells to the olfactory bulb.

A possible source for transplantable neurons in Parkinson's disease are adult olfactory bulb (OB) dopamine (DA) progenitors that originate in the anterior subventricular zone and reach the OB through the rostral migratory stream. We used adult transgenic mice expressing a lacZ reporter directed by an 8.9 kb tyrosine hydroxylase (TH) promoter to investigate the course of DAergic differentiation. Parallel transgene and intrinsic TH mRNA expression occurred during migration of DA interneurons through the mitral and superficial granule cell layers before these cells reached their final periglomerular position. Differential transgene and calcium-calmodulin-dependent protein kinase IV expression distinguished two nonoverlapping populations of interneurons. Transgenic mice carrying a TH8.9kb/lacZ construct with a mutant AP-1 site demonstrated that this element confers OB DA-specific TH gene regulation. These results indicate that DA phenotypic determination is specific to a subset of mobile OB progenitors.

Effects of the menstrual cycle on measures of personality in women with premenstrual syndrome: a preliminary study.

BACKGROUND: Previous studies suggest that women with premenstrual syndrome (PMS) differ from those without PMS in measures of personality. The purpose of this study was to measure the effect of menstrual cycle phase on personality variables in women with and without PMS. METHOD: The Personality Diagnostic Questionnaire-Revised (PDQ-R) was administered in both the follicular and luteal phases to women with PMS (according to National Institute of Mental Health PMS Workshop Diagnostic Guidelines) (N = 40). An asymptomatic control group (N = 20) as well as a symptomatic group of women with DSM-IV-diagnosed recurrent, non-menstrual-cycle-related brief depression (N = 20) also completed the questionnaire in both phases. RESULTS: Only women with PMS demonstrated a significant increase in total PDQ-R score (reflecting overall personality disorder) from the follicular to the luteal phase (p < .01). Women with PMS had significantly higher total PDQ-R scores than the asymptomatic controls during both the follicular (p < .05) and luteal (p < .01) phases, whereas there was no significant difference between women with PMS and symptomatic controls during either phase. Subscale scores fit similar patterns, as did the number of women in each group meeting a cutoff score indicative of the presence of personality dysfunction. CONCLUSION: In this preliminary study, women with PMS were unique in demonstrating a menstrual cycle phase effect on PDQ-R score, while their scores in both phases were closer to symptomatic controls than asymptomatic controls. These findings suggest that personality disorder in women with PMS may have both state- and trait-related components.

Ophthalmic drops causing coma in an infant.

A 1-month-old infant with Peters anomaly had recurrent episodes of unresponsiveness, hypotension, hypotonia, hypothermia, and bradycardia. An extensive medical evaluation determined these episodes to be caused by brimonidine, an anti-glaucoma agent. There is the potential for serious toxic effects from the systemic absorption of topically applied ophthalmic agents in children.

Tension pneumothorax as a complication of video-assisted thorascopic surgery for anterior correction of idiopathic scoliosis in an adolescent female.

STUDY DESIGN: This case report illustrates the occurrence of intraoperative tension pneumothorax, a previously unreported complication occurring during anterior instrumentation for correction of scoliosis by video-assisted surgery. OBJECTIVES: To demonstrate a consequence of overadvancement of a Steinmann pin (guide wire). SUMMARY OF BACKGROUND DATA: Although intraoperative tension pneumothorax is admitted to be a theoretical complication of video-assisted surgery for anterior correction of idiopathic scoliosis, there has yet to be a case reported in the literature. This report presents the first case of this complication. METHODS: A 13-year-old girl who had right thoracic scoliosis with a curve measuring 54 degrees underwent video-assisted surgery discectomy and anterior spinal fusion with instrumentation of T5 through T11. Single-lung ventilation had been achieved with a double-lumen tube and the right lung was deflated. After approximately 4.5 hours of complication-free surgery, intraoperative fluoroscopy showed an approximately 2-cm overadvancement of a guide wire into the opposite hemithorax. Approximately 5 minutes after the overadvancement was corrected, the patient experienced a gradual increase in heart rate and a corresponding gradual decrease in oxygen saturation and both systolic and diastolic blood pressures. Approximately 35 minutes later, it was determined that the patient had sustained a tension pneumothorax of the left hemithorax. RESULTS: The patient underwent urgent partial reinflation of the right lung and a tube thoracostomy of the left thoracic cavity. Vital signs quickly returned to stable levels, and the left lung easily reinflated with the chest tube suction. The patient remained stable after the procedure was resumed (by right lung deflation). The remainder of the surgery and the postoperative course were uneventful. CONCLUSIONS: Although video-assisted surgery continues to gain popularity in the management of spinal deformities, the surgical team must be certain to pay meticulous attention to detail throughout the procedure. The early detection and treatment of complications can be life-preserving.

Monitoring of quality of life in congestive heart failure populations.

The health care system has traditionally focused on treating disease at the point of failure, such as life-saving surgery or intensive medical therapy. As demographics shift more to an aging population, management of health-related quality of life and life-restricting disease becomes more necessary. Prominent among such diseases is congestive heart failure, which must be addressed as a major chronic health condition with its consequent effect on quality of life. This paper examines the methods of monitoring the quality of life in congestive heart failure. Particular attention is paid to congestive heart failure-related questionnaires to derive lifestyle information directly from patients. Comparison is made with general quality of life instruments. Most commonly, these questionnaires are applied to small populations in limited situations. New technology, such as the Internet, has greatly expanded the breadth and depth of health monitors by tracking status directly in patients' homes. This promises new levels of population management for heart disease. (c)2001 by CHF, Inc.

Rapid, labile, and protein synthesis-independent short-term memory in conditioned taste aversion.

Short-term memory is a rapid, labile, and protein-synthesis-independent phase of memory. The existence of short-term memory in conditioned taste aversion (CTA) learning has not been demonstrated formally. To determine the earliest time at which a CTA is expressed, we measured intraoral intake of sucrose at 15 min, 1 hr, 6 hr, or 48 h after contingent pairing of an intraoral infusion of 5% sucrose (6.6 ml over 6 min) and toxic lithium chloride injection (76 mg/kg). Rats were implanted with intraoral catheters to allow presentation of taste solutions at arbitrary times. Intraoral intake was measured under conditions of long-delay, single-trial learning typical of CTA. Rats decreased intraoral intake of sucrose at 15 min after contingent pairing of sucrose and LiCl, but not after noncontingent LiCl or sucrose. Thus CTA learning can be expressed rapidly. To determine if short-term CTA memory is labile and decays in the absence of long-term memory, we measured intraoral intake of sucrose after pairing sucrose with low doses of LiCl. Rats received an intraoral infusion of 5% sucrose (6 ml/6 min); 30 min later LiCl was injected at three different doses (19, 38, or 76 mg/kg). A second intraoral infusion of sucrose was administered 15 min, 1 hr, 3 hr, 4.5 hr, 6 hr, or 48 hr later. The formation of long-term CTA memory was dependent on the dose of LiCl paired with sucrose during acquisition. Low doses of LiCl induced a CTA that decayed within 6 hr after pairing. Central administration of the protein synthesis inhibitor cycloheximide prior to LiCl injection blocked long-term CTA expression at 6 and 48 hr, but not short-term CTA expression at 1 hr. Thus, short-term memory for CTA learning exists that is acquired rapidly and independent of protein synthesis, but labile in the absence of long-term memory formation.

Gastrointestinal safety and tolerance of ibuprofen at maximum over-the-counter dose.

BACKGROUND: Delineation of non-steroidal anti-inflammatory drug (NSAID) gastrointestinal toxicity has largely depended on retrospective epidemiologic studies which demonstrate that lower doses of NSAIDs pose a lower risk of gastrointestinal toxicity. Ibuprofen, a propionic acid NSAID, has, in most such studies, exhibited a favourable profile in terms of gastrointestinal bleeding. Since 1984, ibuprofen has been available as a non-prescription analgesic/antipyretic with a limit of 1200 mg/day for 10 days of continuous use. Trials and spontaneously reported adverse experiences suggest that gastrointestinal symptoms and bleeding are rare. METHODS: This study prospectively evaluated the gastrointestinal tolerability, as compared to placebo, of the maximum non-prescription dose and duration of ibuprofen use in healthy subjects representative of a non-prescription analgesic user population. RESULTS: Gastrointestinal adverse experiences were similar in the placebo and ibuprofen groups (67 out of 413, 16% with placebo vs. 161 out of 833, 19% with ibuprofen). There was no difference between the two groups in the proportion discontinuing due to a gastrointestinal event. Gastrointestinal adverse experiences reported by >/= 1% of subjects were: dyspepsia, abdominal pain, nausea, diarrhoea, flatulence, and constipation. Seventeen (1.4%) subjects had positive occult blood tests: their frequency was comparable between treatments. CONCLUSIONS: When used as directed to treat episodic pain, non-prescription ibuprofen at the maximum dose of 1200 mg/day for 10 days, is well-tolerated.

Intracerebroventricular angiotensin II increases intraoral intake of water in rats.

Ad lib and intraoral intake tests can separate the effects of drugs on the appetitive and consummatory phases of ingestive behavior. Central angiotensin II increases ad lib intake from water bottles, but its effect on intraoral intake has not been examined. Rats with both lateral intracerebroventricular (i.c.v.) cannulas and intraoral catheters were given angiotensin II (100 ng/5 microliters i.c.v.) followed by a 10-min intraoral infusion of water. Angiotensin II increased intraoral intake and increased ad lib water intake from bottles after the intraoral test. Thus angiotensin II increases water intake during both appetitive and consummatory phases of drinking.