Israel Medical Association Journal

Background: Manganism is a central nervous system disorder caused by toxic exposure to manganese. Manganism has been related to occupational exposures, liver diseases, prolonged parenteral nutrition, and abuse of illicit drugs. Initially manifested by a reversible neuropsychiatric syndrome (locura manganica), the main symptoms and signs of manganism are emotional lability, compulsive behavior and visual hallucinations. Locura manganica is followed by an irreversible extrapyramidal syndrome, the onset of which occurs years after chronic exposure.

Objectives: To characterize the regional distribution of Mn[1] in the rat brain after subchronic exposure to Mn. This animal model holds special clinical relevance, reflecting the earlier clinical stages of manganism before chronic exposure to Mn exerts its irreversible effects.

Methods: Sprague-Dawley rats were intravenously injected with MnCl₂ weekly, for a total of 14 weeks – approximately 1/10 of the lifetime of the rat. T1-weighted magnetic resonance imaging was used to detect the distribution of Mn deposition in brain tissues, as evidenced by areas of T1-weighted hyperintense signals.

Results: A consistent region-specific pattern of T1-weighted hyperintensities was observed in the brains of Mn-treated rats. Cortical hyperintensities were prominent in the hippocampus and dentate gyrus. Hyperintensities were also observed in the olfactory bulbs, pituitary gland, optic nerves and chiasma, pons, midbrain tegmentum, habenula, lentiform and caudate nuclei, thalamus, chorioid plexus and cerebellar hemispheres.

Conclusions: Prominent Mn depositions, evidenced by T1-weighted hyperintensities in the hippocampus after subacute exposure to Mn, are compatible with the clinical picture of manganism during its early stages; and may explain its pathophysiology.  

Background: Long QT syndrome is an inherited cardiac disease, associated with malignant arrhythmias and sudden cardiac death.

Objectives: To map and identify the gene responsible for LQTS[1] in an Israeli family.

Methods: A large family was screened for LQTS after one of them was successfully resuscitated from ventricular fibrillation. The DNA was examined for suspicious loci by whole genome screening and the coding region of the LQT2 gene was sequenced.

Results: Nine family members, 6 males and 3 females, age (median and interquartile range) 26 years (13, 46), who were characterized by a unique T wave pattern were diagnosed as carrying the mutant gene. The LQTS-causing gene was mapped to chromosome 7 with the A614V mutation. All of the affected members in the family were correctly identified by electrocardiogram. Corrected QT duration was inversely associated with age in the affected family members and decreased with age.
Conclusions: Careful inspection of the ECG can correctly identify LQTS in some families. Genetic analysis is needed to confirm the diagnosis and enable the correct therapy in this disease

Background: The prevalence of chronic pain in the general population ranges from 10% to over 40%, depending on the definition and the population studied. No large study has been conducted in Israel.

Objectives: To evaluate the prevalence of patients with chronic pain, and characterize them in a large community random sample.

Methods: We conducted a survey of Clalit Health Services members, interviewing them by phone. A random sample of 4063 Clalit members, 25 years or older and Hebrew speakers, were screened for chronic pain, defined as: any pain or discomfort that in the last 6 months has persisted continuously or intermittently for more than 3 months.

Results: Eight percent (n=325) refused to participate. Of the 3738 included in the study, 1722 (46%) reported chronic pain in at least one site. Most of the patients were over 50 years old (62%) (mean age 56 ± 16, range 27–97 years). Women suffered significantly more than men, as did those who were older, less educated and born in Israel and Eastern Europe. Prevalent painful sites were the back (32%), limbs (17%) and head (13%). More than a third reported severe pain and impaired life activities. Only 4.8% of the patients suffering from chronic pain were referred to pain specialists and 11% used complementary medicine. A logistic regression model showed that women and patients with lower education level were the only significant variables predicting higher life impact index and higher pain severity.

Conclusions: We found a high prevalence of chronic pain in the study population. Chronic pain causes severe disturbance to quality of life. A low rate of referral to pain specialists and complementary medicine was observed.

Background: Sarcoidosis is a multisystemic disorder of unknown cause that primarily affects the lungs. The diagnosis is made by the clinical manifestations, radiological findings and histological examination.

Objectives: To review and illustrate the typical and atypical radiological findings of sarcoidosis in the chest.

Methods: We analyzed the radiographic thoracic findings of all patients who had biopsy-proven sarcoidosis over the last 10 years.

Results: There were 100 consecutive patients (36 men and 64 women, age 20–84 years) with an established diagnosis of sarcoidosis. Thoracic lymphadenopathy was detected in 89 patients (89%). Lung parenchyma involvement was found in 60 patients. These changes were variable and included: ground glass attenuation (n=39), multiple small nodules (n= 44) and irregular thickening of the interlobular septa (n=16). Larger nodules (1–3 cm) were identified in 12 patients and frank consolidations were seen in 12 patients. Pleural thickening with subpleural nodules was identified in 17 patients.

Conclusions: Sarcoidosis has a wide variety of radiological manifestations in the chest. Familiarity with the various radiographic findings is important for diagnosis and management.
 

Background: In view of the rising prevalence of obesity, the identification of young adult populations at risk is important for the formulation of intervention and prevention programs.

Objectives: To assess demographic and behavioral factors associated with an increase in body mass index in young healthy adults and to identify the incidence of overweight/obesity in this population.

Methods: Data on anthropometric measures, demographic characteristics, and health behaviors were collected retrospectively for a representative sample of young Israeli adults (11,391 men, 11,280 women) on their release from military service (age 20–22 years) between 1989 and 2003. The incidence of overweight (BMI[1] < 25-< 30 kg/m²), incidence of obesity (BMI ≥ 30 kg/m²), and increase in BMI during military service were calculated.

Results: The average increase in BMI during military service was 1.11 kg/m² in males and 1.08 kg/m² in females. A greater increase was positively associated with low paternal education and smoking cessation, and negatively associated with high physical activity. Twelve percent of subjects with a normal BMI on recruitment became overweight, and 21.7% of overweight subjects became obese. On multivariate logistic regression analysis, a higher incidence of overweight was associated with low education level (in both the subject and his or her father) in both genders, and non-use of oral contraceptives and low level of physical activity in females.

Conclusions: BMI appears to increase significantly during early adulthood. Intervention programs should be targeted specifically at subjects with low education or who started smoking before age 18, and physical activity (especially among females) should be encouraged.

Background: A polymeric diet rich in transforming growth factor-beta 2 used as a single nutrient has been shown to induce remission in 79% of children with Crohn's disease.

Objectives: To summarize the experience of several pediatric gastroenterology units in Israel using a TGFβ2[1]-enriched polymeric diet (Modulen IBD) supplementation in children and adolescents with Crohn's disease.

Methods: In a retrospective study we reviewed the charts of 28 children with Crohn's disease (10 girls, 18 boys) who received, in addition to conventional treatment, Modulen IBD™ as a supplement to their regular nutrition. These children were compared with 18 children supplemented with standard polymeric formula (Ensure Plus®) and 18 children without formula supplementation. We recorded clinical manifestations, growth, and the Pediatric Crohn's Disease Activity Index before and after initiation of the polymeric diet.

Results: The Modulen-treated children showed a significant decrease in PCDAI[2] from 34.3 to 15.7 (P < 0.0001). A significant decrease in PCDAI was recorded also in the Ensure Plus group, from 35 to 22 (P = 0.02) but not in the non-supplemented group. Significant improvements in body mass index (P = 0.01) and erythrocyte sedimentation rate (P = 0.03) were recorded at follow-up (median 3.4 months) only in the Modulen IBD group.

Conclusions: In this cohort of children with Crohn's disease, supplementation of the diet with Modulen IBD as well as supplementation with Ensure Plus was associated with a decrease in PCDAI. The children supplemented with Modulen IBD also showed improvement in BMI[3], suggesting an additional advantage of nutritional therapy in children with this disease.

background: many electrophysiologists recommend implantable cardioverter defibrillators for patients with Brugada syndrome who are cardiac arrest survivors or presumed at high risk of sudden death (patients with syncope or a familial history of sudden death or those with inducible ventricular fibrillation at electrophysiologic study).

objectives: To assess the efficacy and complications of ICD therapy in patients with Brugada syndrome.

Methods: The indications, efficacy and complications of ICD therapy in all patient with Brugada syndrome who underwent ICD implantation in 12 Israeli centers between 1994 and 2007 were analyzed.

Results: there were 59 patients (53 males, 89.8%) with a mean age of 44.1 years. At diagnosis 42 patients (71.2%) were symptomatic while 17 (28.8%) were asymptomatic. The indications for ICD implantation were: a history of cardiac arrest (n=11, 18.6%), syncope (n=31, 52.5%), inducible VF in symptomatic patients (n=14, 23.7%), and a family history of sudden death (n=3, 0.5%). The overall inducibility rates of VF were 89.2% and 93.3% among the symptomatic and a symptomatic patients, respectively (P=NS). During a follow-up of 4-160 (45+-35) months, all patients (except one who died from cancer) are alive. Five patients (8.4%), all with a history of cardiac arrest, had appropriate ICD discharge. Conversely, none of the patients without prior cardiac arrest had appropriate device therapy during 39+-30 month follow-up. Complications were encountered in 19 patients (32%). Inappropriate shocks occurred in 16 (27.1%) due to lead failure/dislodgment (n=5), T wave oversensing (n=2), device failure (n=1), sinus tachycardia (n=4), and supraventricular tachycardia (n=4). One patient suffered a pneumothorax and another a brachial plexus injury during the implant procedure. One patient suffered a late (2 months) perforation of the right ventricle by the implanted lead. Eleven patients (18.6%) required a reintervention either for infection (n=1) or lead problems (n=10). Eight patients (13.5%) required psychiatric assistance due to complications related to the ICD (mostly inappropriate shocks in 7 patients).

Conclusions: In this Israeli population with Brugada syndrome treated with ICD, appropriate device therapy was limited to cardiac arrest survivors while none of the other patients including those with syncope and/or inducible VF suffered an arrhythmic event. The overall complication rate was high.