Motor and non-motor sequence learning in children and adolescents with cerebellar damage.

Cerebellar involvement in motor and non-motor sequence learning was examined with serial reaction time tasks (SRT). Our sample consisted of 8 children and adolescents who had undergone surgical removal of a benign posterior fossa tumor (PFT) during childhood. None of them had undergone chemotherapy or cranial radiation therapy (CRT). Ages ranged from 1-11 years at surgery and 9-17 years at testing. The children were tested not earlier than 2.5 years after surgery (M = 5.9 years), enabling brain plasticity and recovery of functions. Their performance was compared with a matched control sample. The PFT group was not impaired in the implicit learning of sequences, as reflected in their performance in blocks with a repeated sequence, both before and after a random block. However, in the perceptual task, their performance deteriorated more than that of the control group when a random block was introduced, suggesting that it was more difficult for the patients to respond flexibly or change their response set when encountering changing task demands. These results are in line with another study by our group on task switching with the same patients.     

Exogastric neurilemmoma presenting as acute abdomen: Role of computed tomography in diagnosis

A case of subserosal gastric neurilemmoma is hereby presented. This reported case is unique in its clinical presentation including the appearance of acute abdomen and fever subsequent to unremarkable and uneventful upper gastrointestinal endoscopy. The tendency of neurilemmoma to cause mucosal ulceration with fistula formation probably led to this clinical presentation. The role of computed tomography in establishing diagnosis of exogastric tumor is emphasized.     

Childhood Cancer and the Risk of ESKD

BackgroundIncreasing cancer incidence among children alongside improved treatments has resulted in a growing number of pediatric cancer survivors. Despite childhood cancer survivors’ exposure to various factors that compromise kidney function, few studies have investigated the association between childhood cancer and future kidney disease.MethodsTo assess the risk of ESKD among childhood cancer survivors, we conducted a nationwide, population-based, retrospective cohort study that encompassed all Israeli adolescents evaluated for mandatory military service from 1967 to 1997. After obtaining detailed histories, we divided the cohort into three groups: participants without a history of tumors, those with a history of a benign tumor (nonmalignant tumor with functional impairment), and those with a history of malignancy (excluding kidney cancer). This database was linked to the Israeli ESKD registry to identify incident ESKD cases. We used Cox proportional hazards models to estimate the hazard ratio (HR) of ESKD.ResultsOf the 1,468,600 participants in the cohort, 1,444,345 had no history of tumors, 23,282 had a history of a benign tumor, and 973 had a history of malignancy. During a mean follow-up of 30.3 years, 2416 (0.2%) participants without a history of tumors developed ESKD. Although a history of benign tumors was not associated with an increased ESKD risk, participants with a history of malignancy exhibited a substantially elevated risk for ESKD compared with participants lacking a history of tumors, after controlling for age, sex, enrollment period, and paternal origin (adjusted HR, 3.2; 95% confidence interval, 1.3 to 7.7).ConclusionsChildhood cancer is associated with an increased risk for ESKD, suggesting the need for tighter and longer nephrological follow-up.     

Modeling long-term effects attributed to nitrogen dioxide (NO2) and sulfur dioxide (SO2) exposure on asthma morbidity in a nationwide cohort in Israel

Studies have provided extensive documentation that acutely elevated environmental exposures contribute to chronic health problems. However, only attention has been paid to the effects of modificate of exposure assessment methods in environmental health investigations, leading to uncertainty and gaps in our understanding of exposure– and dose–response relationships. The goal of the present study was to evaluate whether average or peak concentration exerts a greater influence on asthma outcome, and which of the exposure models may better explain various physiological responses generated by nitrogen dioxide (NO₂) or sulfur dioxide (SO₂) air pollutants. The effects of annual NO₂ and SO₂ exposures on asthma prevalence were determined in 137,040 17-year-old males in Israel, who underwent standard health examinations before induction to military service during 1999–2008. Three alternative models of cumulative exposure were used: arithmetic mean level (AM), average peak concentration (APC), and total number of air pollution exposure episodes (NEP). Air pollution data for NO₂ and SO₂ levels were linked to the residence of each subject and asthma prevalence was predicted using bivariate logistic regression. There was significant increased risk for asthma occurrence attributed to NO₂ exposure in all models with the highest correlations demonstrated using the APC model. Data suggested that exposure–response is better correlated with NO₂ peak concentration than with average exposure concentration in subjects with asthma. For SO₂, there was a weaker but still significant exposure response association in all models. These differences may be related to differences in physiological responses including effects on different regions of the airways following exposure to these pollutants. NO₂, which is poorly soluble in water, penetrates deep into the bronchial tree, producing asthmatic manifestations such as inflammation and increased mucus production as a result of high gaseous concentrations in the lung parenchyma. In contrast, SO₂, which is highly water soluble, exerts its effects rapidly in the upper airways, leading to similar limited correlations at all levels of exposure with fewer asthmatic manifestations observed. These data indicate that differing exposure assessment methods may be needed to capture specific disease consequences associated with these air pollutants.     

Orthostatic hypotension in internal medicine wards

Objectives: Most studies of orthostatic hypotension (OH) have focused on community-dwelling and institutionalized patient populations. Less is known about OH in hospitalized patients. Moreover, a comprehensive review of OH in internal medicine wards has not been published in the English literature. Our purpose is to provide current information regarding OH in internal medicine inpatients.

Methods: A comprehensive search of medical databases was performed for potentially relevant articles, using the following keywords: postural or orthostatic hypotension, with the combination of hospitalization or internal medicine. Inclusion criteria were: population of patients hospitalized for acute disorders in internal medicine or geriatric wards with a sample size of ≥50 and publication as an original full-length article in the English language. Data from 14 selected studies are reviewed, including: pathophysiology, evaluation, prevalence, manifestations, risk factors, prognosis, and management.

Results: OH is a common and often symptomatic disorder in elderly internal medicine patients. The prevalence of OH in this population ranges from 22–75%. There are substantial discrepancies between the studies reviewed regarding definitions and means of evaluating OH. OH in internal medicine wards is largely non-neurogenic and multifactorial. The main predisposing factors for OH are prolonged bed rest, hypertension, and heart failure. OH in internal medicine wards is managed mainly with non-pharmacologic interventions, and is frequently reversible.

Conclusions: In internal medicine inpatients, OH warrants attention because this disorder is common, potentially dangerous, and treatable. In the hospital setting, OH should be routinely assessed on ambulation, following the current guidelines for OH definition and meaning.     

Mutations in TAX1BP3 Cause Dilated Cardiomyopathy with Septo‐Optic Dysplasia

We describe a Bedouin family with a novel autosomal recessive syndrome characterized by dilated cardiomyopathy and septo‐optic dysplasia. Genetic analysis revealed a homozygous missense mutation in TAX1BP3, which encodes a small PDZ domain containing protein implicated in regulation of the Wnt/β‐catenin signaling pathway, as the causative mutation. The mutation affects a conserved residue located at the core of TAX1BP3 binding pocket and is predicted to impair the nature of a crucial hydrophobic patch, thereby interrupting the structure and stability of the protein, and its ability to interact with other proteins. TAX1BP3 is highly expressed in heart and brain and consistent with the clinical findings observed in our patients; a knockdown of TAX1BP3 causes elongation defects, enlarged pericard, and enlarged head structures in zebrafish embryos. Thus, we describe a new genetic disorder that expands the monogenic cardiomyopathy disease spectrum and suggests that TAX1BP3 is essential for heart and brain development.     

Shortened erythrocyte sedimentation rate evaluation is applicable to hospitalised patients

BackgroundWestergren method, commonly used for erythrocyte sedimentation rate (ESR) determination, is simple and inexpensive. However, the 60 min required for the test are disadvantageous, especially for those departments/facilities where prompt evaluation is necessary. We investigated the possibility that earlier ESR recordings might correlate with standard 60-minute ESR and/or be predictive of the latter.MethodsDemographic and clinical data were collected from 220 randomly chosen adult patients hospitalised for various diseases in a medical department. ESR, determined by slightly modified Westergren method, was recorded at 15, 30 and 60 min. Correlation coefficients (r) between the standard and early ESR measurements were calculated for the entire group and for the separate subgroups divided according to patient age, sex and presence of anaemia or of inflammation.ResultsMean ± SD age of the patients was 61.3 ± 19.6, 55% were males; 45% had some inflammatory condition. Mean ± SD ESR values (mm) at 15, 30 and 60 min were 9.0 ± 12.1, 21.4 ± 21.8 and 35.9 ± 27.5, respectively. A statistically significant correlation was found between ESR measurements at 15 and 60 min (r = 0.833, p < 0.001). However, the strongest correlation was observed between 30 and 60 min measurements (r = 0.926, p < 0.001), irrespective of age, sex and presence of anaemia or of inflammation. Based on the ESR determination at 30 min (X), the predicted ESR value at 60 min (Y) could be calculated by a simple equation: Y = 10.7 + 1.2X.ConclusionSixty-minute ESR values can be predicted by the 30-minute estimation. Shortening the test by half an hour might bear practical importance.     

Mitochondrial pro-apoptotic ARTS protein is lost in the majority of acute lymphoblastic leukemia patients

Acquired resistance towards apoptosis is the hallmark of most if not all types of cancer. We have previously identified and characterized ARTS, a broadly expressed protein localized to mitochondria. ARTS was initially shown to mediate TGF-beta induced apoptosis. Recently, we have found that high levels of ARTS induce apoptosis without additional pro-apoptotic stimuli. Further, ARTS promotes apoptosis in response to a wide variety of pro-apoptotic stimuli. Here, we report that the expression of ARTS is lost in all lymphoblasts of more than 70% of childhood acute lymphoblastic leukemia (ALL) patients. The loss of ARTS is specific, as the related non-apoptotic protein H5, bearing 83% identity to ARTS, is unaffected. During remission, ARTS expression is detected again in almost all patients. Two leukemic cell lines, ALL-1 and HL-60 lacking ARTS, were resistant to apoptotic induction by ara-C. Transfection of ARTS into these cells restored their ability to undergo apoptosis in response to this chemotherapeutic agent. We found that methylation process contributes to the loss of ARTS expression. We conclude that the loss of ARTS may provide a selective advantage for cells to escape apoptosis thereby contributing to their transformation to malignant lymphoblasts. We therefore propose that ARTS can function as a tumor suppressor protein in childhood ALL.