Phenotypic diversity in hypertrophic cardiomyopathy

In recent years, the main focus of human genetic studies on hypertrophic cardiomyopathy (HCM) switched from discovering novel genes and defining disease-causing mutations to studies of mutation distribution in disease populations. Eventually these studies will define genotype-phenotype relationships, which may provide clues to understanding the disease process and help to select the most appropriate treatment strategy. Animal models engineered to recapitulate human disease provide a unique tool to investigate the pathogenic mechanisms and evaluate potential therapies. In this review, we present the spectrum of clinical HCM in the context of the genetic heterogeneity of this common human disease. Recent progress made in understanding molecular pathways that result in cardiac hypertrophy and the factors that modify these processes are discussed.     

Clock drawing task, mini-mental state examination and cognitive-functional independence measure: relation to functional outcome of stroke patients

The use of reliable and valid brief cognitive screening instrument for selecting the appropriate candidates for stroke rehabilitation is crucial. Clinicians often face the question which test should be preferred, that will best correlate with functional outcome. The objective of this study was to compare the clock drawing task with other cognitive tests used for the evaluation of discharge functional outcome in elderly stroke patients. We conducted a retrospective chart study including 151 consecutive patients, admitted for inpatient comprehensive rehabilitation following acute stroke. The clock drawing task (CDT), mini-mental state examination (MMSE) and the cognitive-functional independence measure (cognFIM) were used to assess the cognitive status. Functional status outcome was evaluated by the functional independence measure (FIM), using absolute and relative parameters of efficacy and efficiency. Correlation coefficients (Pearson correlation) between the three cognitive tests resulted in r-values ranging from 0.51 to 0.59 (P<0.001). All three tests correlated significantly with motor outcomes. MMSE did not confer additive value to CDT. It is concluded that CDT is similar to mini-mental and both are somewhat better than cognFIM with respect to the evaluation of functional status outcome following stroke. The correlations between the tests as well as the simplicity of administration favor the use of either CDT or MMSE in the initial assessment of elderly stroke patients.     

Stimulatory GTP regulatory unit Ns and the catalytic unit of adenylate cyclase are tightly associated: mechanistic consequences.

Turkey erythrocyte membranes were solubilized in the mild detergent octylpenta(oxyethylene) [CH3(CH2)7-(OCH2CH2)5OH], which possesses a high critical micelle concentration (approximately equal to 6 mM) and forms small, dynamic micelles. Both the native enzyme Ns(GDP) X C and the p[NH]ppG-preactivated species N's X p[NH]ppG X C' were found to possess the same molecular mass of 215,000 +/- 17,000 daltons. Both enzyme species migrate as a tight complex between Ns and C on both gel permeation columns and on DEAE-Sephacel columns in detergent. The two functional units, Ns and C, remain associated even in dilute detergent solutions and throughout a 300- to 400-fold purification in octylpoly(oxyethylene). These results strongly support the view that Ns and C do not come apart during the process of enzyme activation by the beta-adrenergic receptor. Furthermore, these results strongly support our previous assertion that the beta-adrenergic receptor activation of adenylate cyclase is by a simple "collision coupling" between the receptor and NsC. These results are not compatible with shuttle mechanisms that postulate that Ns physically migrates from the receptor R to the catalytic unit C and back during the activation cycle, as suggested by Citri and Schramm [Citri, Y. & Schramm, M. (1980) Nature (London) 287, 297-300] and by De Lean et al. [De Lean, A., Stadel, J. M. & Lefkowitz, R. J. (1980) J. Biol. Chem. 255, 5108-5117].     

Biopsychosocial exposure to the COVID-19 pandemic and the relative risk of schizophrenia: Interrupted time-series analysis of a nationally representative sample

BackgroundStudies of COVID-19 pandemic biopsychosocial exposure and schizophrenia risk showed contradictory results, were undertaken early in the pandemic, and did not consider lockdowns or COVID-19 infection. Hence, we examined the association between COVID-19 biopsychosocial exposure and incident schizophrenia.MethodsAn interrupted time-series study design was implemented based on Israeli electronic health records from 2013 to 2021 with national coverage. The period coinciding with the COVID-19 pandemic biopsychosocial exposures from March 2020 to February 2021 was classified as exposed, otherwise unexposed. The effect of the COVID-19 pandemic on incident schizophrenia was quantified by fitting a Poisson regression and modeling the relative risk (RR) and corresponding 95% confidence intervals (CI). Three scenarios were projected from the third lockdown to 10 months to forecast incident schizophrenia rates and their associated 95% prediction intervals (PI).ResultsThe total population (N = 736,356) yielded 4,310 cases of incident schizophrenia over time. The primary analysis showed that the period exposed to the COVID-19 pandemic was associated with a reduced RR (RR = 0.81, 95% CI = 0.73, 0.91, p < 0.001). This conclusion was supported in 12 sensitivity analyses, including scrutinizing lockdowns and COVID-19 infection status. Two of three forecast scenarios projected an incident increase (6.74, 95% PI = 5.80, 7.84; 7.40, 95% PI = 6.36, 8.60).ConclusionsThe reduced risk of schizophrenia during the pandemic suggests no immediate triggering of new onsets either by the virus or the pandemic-induced psychosocial adversities. Once restrictions are lifted, the increased projected presentations have implications for clinicians and healthcare policy.     

The effect of enzyme replacement therapy on clinical outcomes in female patients with Fabry disease – A systematic literature review by a European panel of experts

BackgroundHeterozygous females with Fabry disease have a wide range of clinical phenotypes depending on the nature of their mutation and their X-chromosome inactivation pattern; it is therefore important to examine outcomes of enzyme replacement therapy (ERT) in the female patient population specifically. This paper presents the findings of a systematic literature review of treatment outcomes with ERT in adult female patients.MethodsA comprehensive systematic literature review was conducted through January 2017 to retrieve published papers with original data on ERT in the treatment of Fabry disease. The review included all original articles that presented ERT outcomes data on patients with Fabry disease, irrespective of the study type.ResultsClinical evidence for the efficacy of ERT in female patients was available from 67 publications including six clinical trial publications, and indicates significant reductions in plasma and urine globotriaosylceramide (GL-3) accumulation (in female patients with elevated pre-treatment levels) and improvements in cardiac parameters and quality of life (QoL). To date, data are insufficient to conclude on the effects of ERT on the nervous system, gastrointestinal manifestations, and pain in female patients with Fabry disease.ConclusionsThis review of available literature data demonstrates that ERT in adult female patients with Fabry disease has a beneficial effect on GL-3 levels and cardiac outcomes. The current evidence also suggests that ERT may improve QoL in this patient population, though further studies are needed to examine these results.     

Non-traumatic lower limb older amputees: a database survey from a geriatric centre

Purpose: The purpose of this survey was to examine the characteristic of a geriatric population admitted for amputation of a lower limb and to explore some of the factors that may affect the course of their hospital stay. Method: The study took place in the geriatric division of a tertiary general hospital and included a close geriatric-orthopaedic liaison. Two-hundred and forty-one patients were included in the final analysis. Results: Many above knee amputations were performed, which correlated with advanced age. Rates of in hospital mortality and systemic complications were 16% and 19%, respectively. Thirty-three percent of the patients were discharged back home, and only 6% were supplied with an artificial limb. The general condition of most patients remained poor. Conclusion: We conclude that despite a team approach to the care of the geriatric amputee a poor functional result was obtained. By encouraging earlier referrals from the community it is postulated that a reduction in the costly provision of antibiotics would be beneficial and that perhaps lower levels of amputation could be performed thereby enhancing the possibilities for ambulation.     

Effects of induced menopause on Burch colposuspension for urinary stress incontinence.

The clinical and urodynamic short term results after colposuspension for urinary stress incontinence has been studied in a group of young patients in whom menopause was induced surgically and compared with a similarly treated group who did not undergo surgical castration. Clinically, no differences were found in the incidence of diurnal frequency, nocturia, urgency, urge incontinence or stress incontinence between the groups. No urodynamic changes in the cystometric, uroflowmetry and urethral pressure profile measurements were found post-operatively between the two groups. It is concluded that surgically induced menopause in the absence of aging has no effect on the results of colposuspension for urinary stress incontinence in the short term.     

The prognosis of low-birth-weight infants undergoing major surgery

The outcome of 158 infants of low birth weight (LBW) undergoing major surgical procedures was studies. Eighty-four patients were operated on for congenital malformations, mainly atresia of the esophagus, duodenum, and small bowel. Laparotomy for necrotizing enterocolitis (NEC) or idiopathic perforation of the intestine and ligation of a patent ductus arteriosus (PDA) were the most common acquired disorders requiring surgery. In the very LBW (less than 1500 g) group, 73% of the patients underwent operations for acquired lesions. The overall mortality was 23% and for the the very LBW infants 32%. The survival rate was better for the congenital disorders (87%) than the acquired lesions (66%) as a whole, but was about the same in the very LBW subgroups. The survival rate correlated with both birth weight and gestational age in the congenital anomalies, but not in the acquired disorders subgroup; here the prognosis was mainly determined by the severity of the underlying disease. Offprint requests to: O. Zamir     

Adrenocortical reserve of neonates born of long-term,steroid-treated mothers

Since corticosteroids have been shown to be transferred across the human placenta, prolonged administration of these drugs during gestation could be expected to suppress the response of the neonatal adrenal gland. Plasma cortisol levels, before and 30 min after the injection of ACTH (36 g/kg), were determined in six neonates who were exposed in utero to prolonged maternal administration of prednisone. The basal plasma cortisol levels of these neonates (6.15±2.57 g%; mean±SEM) were similar to values obtained in eight healthy neonates (5.19±1.36g%). The increment of cortisol levels after ACTH stimulation (16.4±2.07 g%) of the study patients was larger (P<0.01) than the change (10.3±0.82 g%) observed in six older controls. These results indicate a normal neonatal adrenal reserve after prolonged exposure to corticosteroids during fetal life.