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: Cardiac computed tomography scans influde several extra-cardiac structures such as mediastinum, lung parenchyma and upper abdominal organs. A variety of abnormalities in those structures might be clinically important and in some cases might explain the patient's complaints.

Objectives: To analyze consecutive cardiac computed tomography examinations for the prevalence and clinical significance of extra-cardiac findings.

Methods: Cardiac CT scans of 134 sequential patients (104 males, 30 females) aged 20–77 years (mean 54 years) with suspected coronary artery disease were prospectively and independently reviewed by a consensus of two radiologists for the presence of lung, mediastinal, pleural, upper abdominal and skeletal abnormalities. CT scans with extra-cardiac abnormalities were divided into two groups: group A – defined as "clinically significant" or "potentially significant findings" – consisted of patients requiring further evaluation or follow-up, and group B – "clinically non-significant findings."

Results: Extra-cardiac abnormalities were found in 103 of the 134 patients (76.8%). Group A abnormalities were found in 52/134 patients (39%), while group B abnormalities were seen in 85/134 (63%). The most common abnormalities in group A were non-calcified lung nodules (> 4 mm) noted in 17/134 patients (13%), followed by enlarged mediastinal lymph nodes (> 10 mm) in 14/134 (10%), diaphragmatic hernia (2 cm) in 12/134 (9%), moderate or severe degenerative spine disease in 12/134 (9%), and emphysema and aortic aneurysm in 6 patients each (4.5%). A malignant lung tumor was noted in one patient.

Conclusions: There is a high prevalence of non-cardiac abnormalities in patients undergoing CCT[1]. Clinically significant or potentially significant findings can be expected in 40% of patients who undergo CCT, and these will require further evaluation and follow-up. The reporting radiologist should be experienced in chest imaging and aware of the large variety of non-cardiac findings in CCT that might explain the patient's complaints. 

Background: Patients with non-inflamed appendix have been reported to have had more hospitalizations and emotional disorders before and after the operation than patients with acute appendicitis.

Objectives: To compare abdominal pain characteristics, as well as demographic and psychosocial data in children with histologically confirmed appendicitis compared to non-inflamed appendices.

Methods: Charts of children with suspected appendicitis who had undergone appendectomy were retrospectively reviewed for relevant clinical and laboratory data. The patients or their parents were then contacted by phone and were asked to respond to a detailed questionnaire on abdominal symptoms as well as demographic and psychosocial data.

Results: The study group comprised 156 children: 117 with histologically confirmed appendicitis and 39 with normal appendices. Eighty-two patients (53.2%) were located and interviewed: 62 (54%) with appendicitis and 20 (51%) with normal appendices. Of the 82 children, 16 reported recurrent episodes of abdominal pain before or after surgery: 11 (17.7%) in the appendicitis group and 5 (25%) in the normal appendix group. Only six patients fulfilled the formal criteria for the diagnosis of recurrent abdominal pain: 5 (8%) from the appendicitis group and 1 (5%) from the non-inflamed appendix group (not significant). In addition, no significant statistical differences were found between the groups regarding school performance, behavior and social interaction with peers.

Conclusions: We could not demonstrate an increased incidence of recurrent abdominal pain, nor could we identify significant psychosocial morbidity in those children undergoing a non-inflamed appendectomy.

Background: In recent years, mother to child transmission of human immunodeficiency virus in the west has decreased markedly due to the advent of antiretroviral drugs given during pregnancy, cessation of lactation and careful monitoring of viral load in the perinatal period.

Objective: To assess mother to child transmission of HIV[1] among Ethiopian immigrants and non-Ethiopians in the Jerusalem area.

Methods: We conducted a prospective analysis of all deliveries of HIV-positive women in the Jerusalem district over a 10 year period.

Results: Between 1996 and 2006, 35 HIV⁺ women gave birth to 45 infants. Thirty-one (88%) of these women were of Ethiopian origin and gave birth to 39 infants. Of the 35 HIV⁺ women, 30 were aware of being HIV positive. They gave birth to 40 infants. Another 5 women (14%) were not aware of being HIV⁺ during delivery. They gave birth to five infants. Of the group of known HIV⁺ women, 26 (87%) were Ethiopian immigrants who delivered 34 infants and 4 were non-Ethiopians who delivered 6 infants. In the group of five women not aware of being HIV⁺, all were Ethiopians. Breast-feeding data were available for 32 of the 35 women. Only 2 women (6.2%) breast-fed their babies. Neither was aware of being HIV⁺. In the Ethiopian immigrant group (both known and unknown HIV status), 11 deliveries (28%) were vaginal, 18 (46%) were elective cesarean section and 10 (26%) were delivered by emergency cesarean section. Of the 26 known HIV⁺ Ethiopian women, 3 (12%) refused to take antiretroviral treatment despite repeated counseling. In the non-Ethiopian group, all deliveries were elective cesarean sections. Mother to child transmission of HIV occurred in 4 of the total 45 deliveries (8.8%). Of the 4 transmission cases, 2 occurred among 40 deliveries of known HIV⁺ women (5%), and 2 occurred among the 5 deliveries of women not aware of being HIV⁺ (40%, P = 0.05). In the group of Ethiopian women only, HIV transmission occurred in 4 of 39 deliveries (10%), of which 2 occurred among 34 deliveries (5.8%) of women know to be HIV⁺ and 2 among 5 deliveries (40%) of women not aware of being HIV⁺ (P = 0.08).

Conclusions: Pregnant Ethiopian immigrants whose HIV status was known during pregnancy were at relatively high risk of HIV transmission despite the availability of antiretroviral drugs and counseling. This is likely due to inadequate adherence to ART[2] preventive regimens and is not dissimilar to the poor adherence observed among other immigrant groups in western countries. The substantial proportion of women, all Ethiopians, unaware of being HIV⁺ at delivery, together with the significantly higher HIV transmission in that group compared to women who knew their HIV status, call for a revision of the current Ministry of Health opt-in policy for prenatal HIV screening.

Background: The co-morbidity rate of illicit substance abuse and major mental problems in Israel is far from clear.

Objectives: To investigate the extent of drug abuse in a sample of psychiatric patients hospitalized in a psychiatric hospital and in the psychiatric department of a general hospital in Israel, to compare demographic and other background factors in dual-diagnosis patients with those of abuse-free mental inpatients, and to examine the time correlation between drug abuse and the appearance of major mental problems.

Methods: Our data were derived from self-report and urine tests. The study population comprised 470 consecutively admitted patients – 250 patients in the mental health center and 220 patients in the psychiatric department of the general hospital.

Results: The lifetime prevalence of drug abuse was 24%; cannabis abuse was found in 19.7%, opiates in 5.7%, cocaine in 2.7%, amphetamines in 3.4% and methamphetamine in 1.1%. Active abuse of drugs (during the last month) was registered in 17.3%, cannabis in 11.5%, opiates in 4.9%, amphetamine in 3.8%, cocaine in 1.3% and methamphetamine in 1.1%. We also found that 28.2% of active abusers used two or more substances. In 41.6% the drug abuse appeared prior to symptoms of the mental disorder; in 37.1% the duration of the mental disorders and the drug abuse was relatively similar, and in 21.3% of cases the duration of mental problems was longer than the duration of drug abuse. Dual-diagnosis patients were younger than non-abusers, more often male, unmarried, and of western origin.

Conclusions: Substance abuse (especially cannabis) among hospitalized psychiatric patients in Israel is a growing problem.

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: Dedicated, organ-specific screening clinics have been shown to significantly reduce cancer morbidity and mortality.

Objectives: To establish a dedicated clinic for Clalit Health Service patients at high risk for hereditary gastrointestinal cancer and to provide them with clinical and genetic counseling, diagnostic screening and follow–up.

Results: During the 3 years of the clinic's activity, 634 high risk families, including 3804 at-risk relatives, were evaluated. The most common conditions were hereditary colorectal syndromes, Lynch syndrome (n=259), undefined young-onset or familial colorectal cancer (n=214), familial adenomatous polyposis (n=55), and others (n=106). They entered follow-up protocols and 52 underwent surgical procedures.

Conclusions: Consistent public and professional education is needed to increase awareness of hereditary colorectal cancer and the possibility of family screening, early diagnosis and therapy. The public health services – i.e., the four health management organizations – should provide genetic testing for these patients who, at present, are required to pay for almost all of these available but costly tests. Dedicated colorectal surgical units are needed to provide the specialized therapeutic procedures needed by patients with familial colorectal cancer. Our future plans include adding psychosocial support for these at-risk patients and their families as well as preventive lifestyle and dietary intervention. 

Background: Ocular hypotony is a common unexplained feature of myotonic dystrophy type 1. Spuriously low applanation tonometric readings can be caused by thin corneas, flat corneal curvature and corneal edema.

Objectives: To determine whether structure abnormalities of the cornea cause spuriously low readings in applanation tonometry.

Methods: We utilized a TMS-2N corneal topographer, a NonconRobo SP-6000 Specular microscope and a Corneo-Gage Plus 1A Pachymeter to examine seven patients with DM1[1] and eight healthy controls. Intraocular pressure, central corneal thickness, and endothelial cell density were measured, and simulated keratometry readings were made. Cornea guttata and irregularity of corneal topography patterns were also sought.

Results: The mean intraocular pressure was 9.86 ± 1.29 mmHg for all patients (intraocular operated and non‑operated eyes) and 12.88 ± 1.89 mmHg for the controls (P = 0.000021, two-tailed t-test). Central corneal thickness was 530.57 ± 35.30 micron for all patients and 535.00 ± 39.62 micron for the controls (P = 0.75, two-tailed t-test). Endothelial cell density was 3164 ± 761 cells/mm² for all patients and 3148 ± 395 cells/mm² for the controls (P = 0.94, two-tailed t-test). Simulated keratometry readings were similar in both groups when the operated eyes were excluded. Cornea guttata and irregularity of corneal topography patterns were also noted in the study group.

Conclusions: Corneal thickness, corneal curvature and corneal hydration were within normal limits and thus were not the cause for the low applanation tonometry reading in DM1. The presence of cornea guttata and irregularity of corneal topography patterns in DM1 warrants further investigation. 

Background: Computed tomographic colonography, also known as virtual colonoscopy, is a rapid, non-invasive imaging technique for the detection of colorectal masses and polyps that is becoming increasingly popular.

Objectives: To evaluate the availability, technique, standards of performance and indications for CT colonography in Israel.

Methods: A questionnaire on CT colonography was sent to all radiology departments and private institutions that perform CTC[1] in Israel. We evaluated multiple technical parameters regarding the performance and interpretation of CTC as well as radiologists' training and experience.

Results: Fourteen institutions – 7 hospitals and 7 private clinics – participated in the study. Most of the small radiology departments and nearly all of the more peripheral radiology departments do not perform CTC studies. Since 2000 and until March 2007, a total of 15,165 CTC studies were performed but only 14% (2123 examinations) were performed at public hospitals and 86% (13,042 exams) at private clinics. CTC was performed after an incomplete colonoscopy or for various contraindications to endoscopic colonoscopy in up to a third of cases. In the various institutions patients were self-referred in 20–60% of cases, more commonly in private clinics. All CTC examinations were performed on 16–64 slice CT scanners and only a small minority was performed on 4-slice scanners in 2001. All but one center used low radiation protocols. Nearly all facilities used a 2 day bowel-cleansing protocol. All except one facility did not use stool tagging or computer-aided diagnosis. All facilities inflated the colon with room air manually. All institutions used state-of-the-art workstations, 3D and endoluminal navigation, and coronal multi-planar reconstructions routinely. There are 18 radiologists in the country who perform and interpret CTC studies; half of them trained abroad. Ten of the radiologists (56%) have read more than 500 CTC studies.

Conclusions: In Israel, CTC examinations are performed by well-trained and highly experienced radiologists using the latest CT scanners and workstations and adhering to acceptable CTC guidelines.  

The frequency of pregnancy-associated breast cancer, a rare but serious occurrence, may increase in light of the secular trends for lower parity in general and for an older age at first full-term delivery in particular. Data on PABC[1] in individuals who are at high risk for breast cancer are limited. A computerized search of PUBMED showed that the reported incidence of PABC is 1:3000 pregnancies; it is often diagnosed at an advanced stage and its prognosis is inferior compared to non-PABC. Carriers of mutations in the genes BRCA1/2 may present a specific high risk group for PABC especially at younger ages. Women treated with fertility treatment drugs may be at a higher risk for PABC as well.