Anomalous origin of the main stem of the left coronary artery from the pulmonary trunk presenting with left ventricular hypertrophy

Patients with anomalous origin of the left coronary artery from the pulmonary trunk may present with paroxysmal angina on exertion, congestive heart failure, dyspnoea, syncope or sudden death. The association of such anomalous origin of the left coronary artery from the pulmonary trunk with a hypertrophic left ventricle is extremely rare. In our cohort of patients with anomalous origin of the left coronary artery from the pulmonary trunk, two presented with a hypertrophic left ventricle. We discuss these cases, accompanied by a review of the English literature describing different morphological anomalies of the coronary arteries associated with left ventricular hypertrophy. Whether the hypertrophy is a result of the evolvement of the collateral coronary system, or due to an additional pathological gene for hypertrophic obstructive cardiomyopathy, remains an enigma. The hypertrophy may have served as a compensatory mechanism accounting for the atypical clinical presentation. We further discuss the possible factors associating the occurrence of anomalous origin of the left coronary artery from the pulmonary trunk and myohypertrophy, supported by the documentation of the regression of hypertrophy following surgical correction of the anomalous arterial origin as seen in our patients.     

Dissociation of cognitive from affective components of theory of mind in schizophrenia

Patients suffering from schizophrenia show impaired emotional and social behavior, such as misinterpretation of social situations and lack of theory of mind. However, there is conflicting evidence regarding their ability to perform on theory of mind tasks. Based on previous findings with patients suffering from prefrontal damage, the present study suggests that the behavioral deficit of schizophrenic patients may be due to impaired 'affective theory of mind' abilities, rather than to a general impairment in theory of mind. To test this hypothesis we assessed the ability of 22 schizophrenic patients and 55 age-matched healthy controls, to judge first and second order affective vs. cognitive mental state attribution, based on eye gaze. The relationships between negative and positive symptoms of schizophrenia, and affective and cognitive theory of mind were also assessed. Results indicated that while healthy controls made fewer errors on affective as compared to cognitive theory of mind conditions, schizophrenic patients showed a less prominent trend. Although the pattern of reaction time did not differ significantly between groups, the patients made significantly more errors in the affective conditions, as compared to controls. Furthermore, correlation analysis indicated that impaired affective theory of mind in these patients correlated with their level of negative symptoms. These results indicate that individuals with high level of negative symptoms of schizophrenia may demonstrate selective impairment in their ability to attribute affective mental states. These findings offer new insight into the affective facets of social behavior that may underlie the profound behavioral disturbances observed in schizophrenia.     

Endocrine effects of valproate in adolescent girls with epilepsy

Summary:  Purpose: To investigate the effect of epilepsy and/or valproate (VPA) monotherapy on physical growth, weight gain, pubertal development, and hormonal status in adolescent girls with epilepsy.
Methods: The study group included 88 consecutive female patients with epilepsy aged 6–20 years (28 premenarche, 60 postmenarche) attending an endocrinology institute of a major tertiary center. Forty-five patients were under treatment with VPA, and 43 were before treatment initiation. The groups were compared for the relevant biochemical, anthropometric, ultrasonographic, and endocrine parameters.
Results: No statistically significant differences were found in any of the parameters studied between the groups, as a whole or by menarche status. The treated postmenarcheal subgroup had a higher mean testosterone level than the untreated postmenarcheal controls (1.83 ± 0.65 vs. 0.88 ± 0.24, p = 0.006). Body mass index–standard deviation score (BMI-SDS) was 0.75 in the treated group and 0.63 in the untreated group; rates of obesity were 16.3% and 15.5%, respectively. No between-group differences were found in menses irregularities, hirsutism, or acne. No correlation was found between duration or dosage of treatment and BMI-SDS, height–SDS, or androgen level. The treated group had higher levels of thyroid-stimulating hormone and lower levels of free thyroxine than did the untreated group, although still within normal range.
Conclusions: Long-term treatment with VPA in girls with epilepsy is associated with increased testosterone levels after menarche, without clinical hyperandrogenism, polycystic ovary syndrome, or an increase in BMI-SDS. VPA is a good treatment option in this age group but should be accompanied by careful endocrine observation.     

Clinical features of community-acquired <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> urinary tract infections in children

This retrospective chart review sought to determine clinical, radiological, and gender-associated characteristics of community-acquired Pseudomonas aeruginosa (PA) urinary tract infections (UTIs) among children admitted to two medical centers. The records of 73 children with community-acquired PA UTIs were compared with records of 109 children with community-acquired UTIs caused by other pathogens. The mean age of both groups was similar. The PA UTI group included more boys. Features significantly more common in the PA UTI group were the number of patients who had undergone urinary tract surgery, patients with skeletal and/or neurological malformation, patients with >1 previous episode of UTI, patients on prophylactic antibiotic treatment on admission, and patients with pathological renal ultrasound and voiding cystourethrography (VCUG) findings. Multivariate logistic regression analysis revealed the following to be associated with PA UTI: >1 episode of UTI in the past [odds ratio (OR) = 35.5; 95% confidence interval (CI) 11.6–108.7], previous urinary tract surgery (OR = 34.1; 95% CI 7.00–166.2), and pathological VCUG results (OR = 2.62; 95% CI 0.96–7.15). In conclusion, PA UTI is associated with >1 previous UTI, urinary tract abnormalities, and past urinary tract surgery. We recommend that when UTI is suspected in children with these risk factors, a thorough radiologic investigation, including a VCUG, should be considered. Drs. Goldman and Rosenfeld-Yehoshua contributed equally to this work.     

Asymmetric fluorogenic organophosphates for the development of active organophosphate hydrolases with reversed stereoselectivity

In order to enhance the enzymatic detoxification rate of organophosphorus (OP) nerve agents we have searched for more active variants of recombinant mammalian paraoxonase (PON1). We have previously identified three key positions in PON1 that affect OP hydrolysis: Leu69, Val346 and His115, that significantly enhance the hydrolysis of cyclosarin (GF), soman, chlorpyrifos-oxon (ChPo), O-isopropyl-O-(p-nitrophenyl)methylphosphonate (IMP-pNP) and diisopropyl fluorophosphate (DFP). GC/FPD analysis compared to residual AChE inhibition assay displayed stereoselective hydrolysis of GF, soman and IMP-pNP, indicating that wild type PON1 and its variant V346A are more active toward the less toxic P(+) optical isomer. In order to obtain new PON1 variants with reversed stereoselectivity, displaying augmented activity toward the more toxic isomer P(-) of nerve agents, we synthesized new asymmetric fluorogenic OPs (Flu-OPs). Six Flu-OPs were prepared containing either ethyl (E), cyclohexyl (C) or pinacolyl (P) alkyl radicals attached to methyl-phosphonyl (MP) moiety analogous to the structure of VX, GF and soman, respectively. The fluorescent moieties are either 3-cyano-4-methyl-7-hydroxy coumarin (MeCyC) or 1,3-dichloro-7-hydroxy-9,9-dimethyl-9H-acridin-2-one (DDAO). The kinetics of AChE and BChE inhibition by these new Flu-OPs display k(i) values 8.5x10(4) to 8.5x10(7) and 5x10(4) to 2x10(6)M(-1)min(-1), respectively. EMP-MeCyC and EMP-DDAO are the most active inhibitors of AChE whereas CMP-MeCyC and CMP-DDAO are better inhibitors of BChE than AChE, indicating accommodation of bulky cyclohexyl group inside the active site of BChE. PMP-MeCyC and PMP-DDAO are the least active inhibitors of both AChE and BChE. CMP-MeCyC and CMP-DDAO were significantly detoxified only by the five-site mutations PON1 variant L69V/S138L/S193P/N287D/V346A. Degradation kinetics of Flu-OPs measured by increase in absorbance of the released fluorogenic group was fit by a two exponential function, indicating faster hydrolysis of the less toxic optical isomer. Interestingly, wt PON1 caused only 50% degradation of racemic EMP-MeCyC, CMP-MeCyC and CMP-DDAO indicating complete hydrolysis of P(+) isomer. This remarkable stereoselectivity was used for the enzymatic separation of the P(-) isomer of CMP-MeCyC. The bimolecular rate constant k(i) for human AChE inhibition by the isolated P(-) isomer of CMP-MeCyC is five-fold larger than that of its P(+) isomer. The marked preference of wt PON1 toward P(+) stereo-isomer of CMP-MeCyC and CMP-DDAO renders their P(-) stereo-isomers suitable for the selection of new OP hydrolase variants with reversed stereoselectivity.     

THE EXPERIENCE OF BLACK CONSUMERS IN THE MENTAL HEALTH SYSTEM—IDENTIFYING BARRIERS TO AND FACILITATORS OF MENTAL HEALTH TREATMENT USING THE CONSUMERS' PERSPECTIVE

Research has shown that relative to Whites, Blacks are less likely to seek outpatient mental health treatment and more likely to seek emergency services. Furthermore, Blacks often terminate treatment prematurely. The goal of the present study was to identify barriers to and facilitators of mental heath treatment among Blacks who have a documented need for mental health services. Thirty-four Black mental health consumers were interviewed for this purpose. Comments were categorized into four main categories: (a) barriers to treatment, (b) treatment facilitators, (c) recommendations for improvement of services, and (d) advice to potential consumers. The most common barriers were the importance of family privacy, lack of knowledge regarding available treatments, denial of mental health problems, and concerns about stigma, medications, and treatment. Participants also reported system barriers, such as not receiving appropriate information about services or receiving inadequate, dehumanizing services. Acknowledging the need for mental health services, having a supportive environment, and positive past treatment experiences were identified as treatment facilitators. Community outreach, adequate follow-up, and coordination of services also were important messages delivered by consumers. The results of this study indicate the importance of educating the general public, not just mental health consumers, about the nature of mental illness and available services.     

Transfer of perceptual learning of depth discrimination between local and global stereograms

Several previous studies reported differences when stereothresholds are assessed with local-contour stereograms vs. complex random-dot stereograms (RDSs). Dissimilar thresholds may be due to differences in the properties of the stereograms (e.g. spatial frequency content, contrast, inter-element separation, area) or to different underlying processing mechanisms. This study examined the transfer of perceptual learning of depth discrimination between local and global RDSs with similar properties, and vice versa. If global and local stereograms are processed by separate neural mechanisms, then the magnitude and rate of training for the two types of stimuli are likely to differ, and the transfer of training from one stimulus type to the other should be minimal. Based on previous results, we chose RDSs with element densities of 0.17% and 28.3% to serve as the local and global stereograms, respectively. Fourteen inexperienced subjects with normal binocular vision were randomly assigned to either a local- or global- RDS training group. Stereothresholds for both stimulus types were measured before and after 7700 training trials distributed over 10 sessions. Stereothresholds for the trained condition improve for approximately 3000 trials, by an average of 0.36 ± 0.08 for local and 0.29 ± 0.10 for global RDSs, and level off thereafter. Neither the rate nor the magnitude of improvement differ statistically between the local- and global-training groups. Further, no significant difference exists in the amount of improvement on the trained vs. the untrained targets for either training group. These results are consistent with the operation of a single mechanism to process both local and global stereograms.