II. Hypersociability in Williams Syndrome

Studies of abnormal populations provide a rare opportunity for examining relationships between cognition, genotype and brain neurobiology, permitting comparisons across these different levels of analysis. In our studies, we investigate individuals with a rare, genetically based disorder called Williams syndrome (WMS) to draw links among these levels. A critical component of such a cross-domain undertaking is the clear delineation of the phenotype of the disorder in question. Of special interest in this paper is a relatively unexplored unusual social phenotype in WMS that includes an overfriendly and engaging personality. Four studies measuring distinct aspects of hypersocial behavior in WMS are presented, each probing specific aspects in WMS infants, toddlers, school age children, and adults. The abnormal profile of excessively social behavior represents an important component of the phenotype that may distinguish WMS from other developmental disorders. Furthermore, the studies show that the profile is observed across a wide range of ages, and emerges consistently across multiple experimental paradigms. These studies of hypersocial behavior in WMS promise to provide the groundwork for crossdisciplinary analyses of gene-brain-behavior relationships.     

Phase II study of troxacitabine, a novel dioxolane nucleoside analog, in patients with refractory leukemia.

PURPOSE: To investigate the activity of a novel dioxolane L-nucleoside analog, troxacitabine (L-(-)-OddC, BCH-4556), in patients with refractory leukemia. PATIENTS AND METHODS: Study participants were patients with refractory or relapsed acute myeloid (AML) or lymphocytic (ALL) leukemia, myelodysplastic syndromes (MDS), or chronic myelogenous leukemia in blastic phase (CML-BP). Troxacitabine was provided as an intravenous infusion for more than 30 minutes daily for 5 days at a dose of 8.0 mg/m(2)/d (40 mg/m(2) per course). Courses were given every 3 to 4 weeks according to antileukemic efficacy. RESULTS: Forty-two patients (AML, 18 patients; MDS, one patient; ALL, six patients; CML-BP, 17 patients) were treated. Median age was 51 years (range, 23 to 80 years); 22 patients were male. Stomatitis was the most significant adverse event, with three patients (7%) and two patients (5%), respectively, experiencing grade 3 or 4 toxicity. Ten patients (24%) had grade 3 hand-foot syndrome, and two patients (5%) had grade 3 skin rash. One patient (2%) had grade 3 fatigue and anorexia. Marrow hypoplasia occurred between days 14 and 28 in 12 (75%) of 16 assessable patients with AML. Two complete remissions and one partial remission (18%) were observed in 16 assessable patients with AML. None of six patients with ALL responded. Six (37%) of 16 assessable patients with CML-BP experienced a return to chronic-phase disease. CONCLUSION: Troxacitabine has significant antileukemic activity in patients with AML and CML-BP.     

Material and human resources for neonatal resuscitation in public maternity hospitals in Brazilian state capitals

CONTEXT AND OBJECTIVE: In 2002, the early neonatal mortality rate in Brazil was 12.42 per thousand live births. Perinatal asphyxia was the greatest cause of neonatal death (about 23%). This study aimed to evaluate the availability of the resources required for neonatal resuscitation in delivery rooms of public hospitals in Brazilian state capitals. DESIGN AND SETTING: Multicenter cross-sectional study involving 36 hospitals in 20 Brazilian state capitals in June 2003. METHODS: Each Brazilian region was represented by 1-4% of its live births. A local coordinator collected data regarding physical infrastructure, supplies and professionals available for neonatal resuscitation in the delivery room. The information was analyzed using the Statistical Package for the Social Sciences, version 10. RESULTS: Among the 36 hospitals, 89% were referral centers for high-risk pregnancies. Each institution had a monthly mean of 365 live births (3% < 1,500 g and 15% < 2,500 g). The 36 hospitals had 125 resuscitation tables (3-4 per hospital), all with overhead radiant heat, oxygen and vacuum sources. Appropriate equipment for pulmonary ventilation was available for more than 90% of the 125 resuscitation tables. On average, one pediatrician, three nurses and five nursing assistants per shift worked in the delivery rooms of each institution. Out of the 874 pediatricians and 1,037 nursing personnel that worked in the delivery rooms of the 36 hospitals, 94% and 22%, respectively, were trained in neonatal resuscitation. CONCLUSIONS: The main public maternity hospitals in Brazilian state capitals have the resources to resuscitate neonates at birth.     

An investigation of the population impact of variation in HbA<Subscript>1c</Subscript>levels in older people in England and Wales: From a population based multi-centre longitudinal study

Background  

Diabetes is common in the older population and is increasing. Glycated hemoglobin (HbA_1c) is an indicator of average blood glucose concentration over the past three months. The HbA_1c test is currently one of clinical methods used to check diabetes control. Recent studies have suggested diabetes is a risk factor for dementia, cognitive dysfunction and physical disability. In addition, there have reported the relationship between HbA_1c and mortality on all cause, cardiovascular disease and cognitive function, but few studies have investigated the relationship concentrating on the older population.     

Maternal serum creatine kinase does not predict tubal pregnancy

Purpose: Our purpose was to validate prospectively the predictive value of maternal serum creatine kinase in the evaluation of ectopic pregnancy. Methods: Fifty-one consecutive pregnant first-trimester patients who presented for suspected abnormal pregnancy were enrolled. Maternal serum samples were obtained and assayed for creatine kinase. Patients were subsequently evaluated for abnormal pregnancy by serial quantitative hCG levels, transvaginal ultrasonography, and surgery when appropriate. A receiver operating characteristic (ROC) curve was generated comparing intrauterine to extrauterine (ectopic) pregnancy. Results: Of 51 patients, 18 had an ectopic pregnancy, 16 had a spontaneous abortion, and 17 had an ongoing intrauterine pregnancy. The ROC curve revealed that maternal serum creatine kinase had no ability to predict ectopic pregnancy. Conclusions: Maternal serum creatine kinase is not a reliable predictor of tubal pregnancy.Presented at the Forty-Second Annual Meeting of the Society for Gynecological Investigation, March 15–18, 1995, Chicago, Illinois.     

Morphology of the posterior junctional area in atrioventricular septal defects.

The location and size of the coronary sinus in hearts with atrioventricular septal defect were investigated in relation to the known disposition of the atrioventricular conduction axis. We examined the morphology in 40 hearts and supplemented this series with two other hearts that had been serially sectioned previously. The coronary sinus received drainage from a persistent left superior caval vein in 5 hearts. Six cases of 40 had malalignment of the septal structures relative to the crux of the heart. In these, the conduction axis was anticipated to course in the position where the inlet ventricular septum met the atrioventricular junction. The coronary sinus terminated in the left atrium in 4 hearts: 2 in the morphological series and 2 that were sectioned for histological studies. The sectioned hearts showed the atrioventricular conduction axis in the usual position for the defect, unrelated to the coronary sinus. The principle that the node and penetrating bundle are located at the intersection of the ventricular septum with the atrioventricular junction holds good despite the variability of the coronary sinus.     

Ventricular haemangioendothelioma diagnosed in life.

A case of right ventricular outflow obstruction is described in which the electrocardiogram and chest x-ray film suggested a cardiac tumour. Cardiac catheterisation confirmed outflow obstruction and angiography showed a tumour. At operation a haemangioendothelioma was found.     

Evaluation of diazepam and pyridoxine as antidotes to isoniazid intoxication in rats and dogs

Because information regarding efficacious treatment of acute isoniazid (INH) toxicity is incomplete and controversial, diazepam and pyridoxine were investigated as iv antidotes in rats and dogs following administration of po lethal doses of INH. There is a marked species variation in the lethality of INH; the lowest consistently lethal dose is 1500 mg/kg for rats and 75 mg/kg for dogs. Of the two species, the dog more closely approximates man's sensitivity to the lethal effect of INH overdose (80–150 mg/kg). Species variation was also observed in the effects of the antidotes. Diazepam exerted dose-related protection against convulsions in rats; paradoxically, survival was increased by the lowest dose (1 mg/kg) but not by higher doses. In dogs, however, diazepam failed to prevent convulsions but provided dose-related protection against death. Pyridoxine, in rats, did not protect against INH toxicity, but in dogs it showed dose-related effectiveness against convulsions, and all doses (75–300 mg/kg) prevented lethality. Significantly, the highest dose of pyridoxine tested in rats (750 mg/kg) was substantially below the optimal pyridoxine-to-INH antidotal ratio recommended for man (a dose that at least equals the amount of INH ingested), but that dose of pyridoxine would be larger than its LD50 for rats. Combined administration of diazepam with pyridoxine protected against convulsions and death in rats and dogs. Used concurrently, the two antidotes are clearly synergistic for controlling the manifestations of experimental INH overdose. These results have important implications for the management of acute INH intoxication in man.     

A Study of the Characteristics of Certain Rh Antibodies Preferentially Detectable by Enzyme Technique

Abstract. Antibodies of various specificities which share the property of reacting by enzyme technique but either weakly or not at all by antiglobulin have been studied. They are found to occur among both IgG and IgM immunoglobulins. They are able to effect a positive antiglobulin reaction after being 'built up' by the formation of a globulin-antiglobulin lattice on the red cells. In general the IgG antibodies require more 'build-up' than the IgM. Various reasons for the failure of these antibodies to be detected by the antiglobulin technique as it is normally performed, are discussed.