Israel Medical Association Journal

Background: Magnetic resonance imaging of the breast has emerged as a valuable imaging tool in addition to conventional imaging modalities. It has high sensitivity for malignant lesions, and can detect mammographically, sonographically and clinically occult cancers. “MR only” lesions are best biopsied under MR guidance; however, this may be a challenging task.

Objectives:  To evaluate our initial clinical experience with MR-guided core needle breast biopsy and MR-guided needle localization.

Methods: We retrospectively evaluated 81 women with 97 lesions, who were scheduled for guided core needle biopsy or MR-guided needle localization followed by surgery. Lesions were categorized as malignant, high risk, or benign according to the BI- RADS MR classification system. MR findings were compared with final histopathology or with follow-up imaging findings.

Results: Fifteen (16%) lesions were malignant (9 invasive ductal carcinoma, 2 invasive lobular carcinoma, 4 ductal carcinoma in situ); 7 (7%) lesions were high risk (4 atypical ductal hyperplasia, 3 radial scars); 75 (77%) lesions were benign, mainly fibrocystic changes. Other benign findings were sclerosing adenosis, pseudoangiomatous stromal hyperplasia, fat necrosis, intraductal papilloma, fibroadenoma, capillary hemangioma, and florid ductal hyperplasia. No major complications were encountered.
Conclusions: MR-guided interventional procedures of the breast are accurate, safe and feasible methods for sampling breast lesions detected only by MR and have become a significant tool in the management of certain patients.

Background: Acute kidney injury remains a common significant clinical problem. Yet there are scant data in Israel on the incidence of hospital-acquired AKI[1] and on diagnosis validity.

Objectives: To describe the epidemiology of AKI among hospitalized patients in the Western Galilee Hospital, Nahariya, compare discharge summaries to laboratory diagnosis, and investigate the impact of AKI on mortality and length of stay.

Methods: Computerized medical and laboratory data of 34,802 hospitalized subjects were collected. AKI was diagnosed according to three different definitions. We calculated the sensitivity and specificity of AKI based on ICD-9 diagnosis compared to patient's laboratory data as the gold standard.

Results: The overall AKI annual incidence rate was 1–5.1%, depending on the AKI definition used. The incidence of AKI based on ICD-9 diagnosis was significantly lower compared to the laboratory-based diagnosis. Average in-hospital length of stay was 2.4 times longer among patients with AKI compared to subjects without this condition. Furthermore, the in-hospital death rate among AKI patients was 14 times higher than among non-AKI hospitalized subjects, with a positive association between AKI severity and risk of death.

Conclusions: Using AKI laboratory diagnosis as the gold standard revealed ICD-9 diagnosis to be 9.1% sensitive and 99.4% specific. Hospital-acquired AKI is a major contributor to prolonged length of stay and high mortality rates; therefore, interventions to reduce in-hospital disease incidence are required.

Background: Despite progress in medical and surgical care the mortality rate of congenital diaphragmatic hernia remains high. Assessment of short-term outcome is important for comparison between different medical centers.

Objectives: To evaluate the short-term outcome of infants born with symptomatic CDH[1] and to correlate demographic and clinical parameters with short-term outcome.

Methods: We performed a retrospective cohort study in which demographic, obstetric and perinatal characteristics were extracted from infants' files. For comparison of categorical variables chi-square test and Fisher's exact test were used and for continuous variables with categorical variables the Mann-Whitney test was used. Sensitivity and specificity were estimated by receiver operator curve.

Results: The study group comprised 54 infants with CDH, of whom 20 (37%) survived the neonatal period. Demographic characteristics were not associated with survival. Regarding antenatal characteristics, absence of polyhydramnion and postnatal diagnosis were correlated with better survival. Apgar scores (above 5 at 1 minute and 7 at 5 minutes), first arterial pH after delivery (above 7.135) and presence of pulmonary hypertension were significantly correlated with survival. Also, infants surviving up to 6 days were 10.71 times more likely to survive the neonatal period.

Conclusions: The survival rate of symptomatic newborns with CDH at our center was 37% for the period 1988–2006. Prenatal diagnosis, Apgar score at 5 minutes and first pH after delivery were found to be the most significant predictors of survival. Prospective work is needed to evaluate the long-term outcome of infants with CDH.

Background: Sickle cell anemia is a hemolytic anemia caused by a single mutation in position 6 of the β globin molecule. About 80 patients with SCA[1] in northern Israel are currently receiving treatment.

Objectives: To assess a screening program in northern Israel aimed at detecting couples at risk for having offspring with SCA.

Methods: Since 1987, screening for β thalassemia in pregnant women in northern Israel has been conducted, and from 1999 all the samples were also tested for hemoglobin S, Hgb C, Hgb D, Hgb O Arab and others.

Results: During the 20 year period 1987–2006 a total of 69,340 women were screened; 114 couples who carried Hgb S were detected and 187 prenatal diagnoses were performed in couples at risk for having an offspring with Hgb S. The mean gestational age was 13 ± 4 weeks. Fifty-four of those diagnoses revealed affected fetuses and in 4 cases the couple declined to perform therapeutic abortion.

Conclusions: The economic burden to the health services for treating SCA patients is about U.S.$ 7000 per year, and the institution of prevention programs has proven cost-effective in populations with a high frequency of carriers. Since our program is aimed to also detect β thalassemia, a disease that is more frequent in this area (> 2.5%), the added cost for the prevention of SCA is less significant in spite a low incidence of the S gene in our population, namely < 1%.

Background: Uncorrected refractive error is the leading cause of visual impairment in children. In 2002 a screening project was launched in Israel to provide data on the effectiveness of the illiterate E-chart in identifying Jewish and Arab schoolchildren in need of a comprehensive eye examination.

Objectives: To present the aims, design and initial results of the visual screening project and the prevalence of vision abnormality in the study population.

Methods: A cross-sectional population-based study was conducted during 2002–2003 among first- and eighth-graders in 70 schools in northern Israel. The nurse's test included use of the illiterate E-chart to measure visual acuity. The medical examination included vision history, clinical eye examination, VA[1] and retinoscopy. The ophthalmologist's evaluation as to whether a child needed a referral for diagnostic procedures, treatment and/or follow-up was recorded and compared with explicit referral criteria formulated after data collection.

Results: Of 1975 schoolchildren, 31% had abnormal VA, defined as VA worse than 6/6 in at least one eye, and a quarter had VA equal or worse than 6/12 in both eyes. The prevalence of vision abnormality among the children was 22.4% when based on the evaluation of the field ophthalmologist and 26.1% when based on two sets of explicit severity scores and referral criteria.

Conclusions: Vision abnormality is a significant health problem among northern Israeli schoolchildren. This project is unique in scope and importance, providing evidence to assist policy making with regard to vision screening for schoolchildren (including data on test reliability and validity) and optimal VA cutoff level, and confirming the need for clinical guidelines regarding referral criteria.

Background: High levels of plasma homocysteine constitute a risk for cardiovascular disease. Physical activity, known to reduce CVD[1] risk, has been related to levels of Hcy[2]. Recently, higher Hcy was shown to be associated with lower cardiovascular fitness in women but not in men.

Objectives: To further explore the relationship between cardiorespiratory fitness and plasma total homocysteine levels in a large cohort of adult males and females.

Methods: This cross-sectional study included 2576 fitness and Hcy examinations in adults (62% males) aged 30–59 years, randomly drawn from a population undergoing a periodic health examination in the Sheba Medical Center's Executive Screening Survey. Blood tests were collected for tHcy[3] and a sub-maximal exercise test was performed to estimate cardiorespiratory fitness. Information on CVD/CVD risk factors (coronary heart disease, cerebrovascular accident, diabetes, hypertension or dyslipidemia) was self-reported.

Results: Mean tHcy plasma levels were 14.4 ± 7.7 and 10.2 ± 3.0 µmol/ml, and mean maximal oxygen uptake 36.5 ± 11.7 and 29 2 ± 9.5 ml/kg/min for males and females, respectively. A multiple regression analysis, adjusting for age, body mass index and CVD/CVD risk factors, showed no association between cardiorespiratory fitness and level of tHcy in males (P = 0.09) or in females (P = 0.62).

Conclusions: In this sample no relationship was found between level of cardiorespiratory fitness and plasma tHcy in men or women. The inconsistency of findings and the small number of studies warrant further research of the association between cardiorespiratory fitness and tHcy, an association that may have clinical implications for the modifications of cardiovascular risk factors.

Background: Foodborne Salmonella enterica outbreaks constitute both a threat to public health and an economic burden worldwide.

Objectives: To characterize the pathogen(s) involved and possible source of infection of an outbreak of acute gastroenteritis in a banqueting hall in Jerusalem.

Methods: We conducted interviews of guests and employees of the banqueting hall, and analyzed food items, samples from work surfaces and stool cultures.

Results: Of 770 persons participating in three events on 3 consecutive days at a single banqueting hall, 124 were interviewed and 75 reported symptoms. Salmonella enterica, serovar Enteritidis, phage type C-8, was isolated from: 10 stool cultures (eight guests, one symptomatic employee and one asymptomatic employee) and a sample of a mayonnaise-based egg salad. Pulsed-field gel electrophoresis[c1]  of the isolates revealed an identical pattern in the outbreak isolates, different from SE C-8 controls. A culture-positive, asymptomatic employee was linked to all three events. After a closure order, allowing for cleaning of the banqueting hall, revision of food preparation procedures and staff instruction on hygiene, the banqueting hall was reopened with no subsequent outbreaks.

Conclusions: It is often difficult to pinpoint the source of infection in S. enterica outbreaks. Using molecular subtyping methods, a link was confirmed between patients, a food handler, (presumably a carrier) and a food item – all showing an identical specific Salmonella enterica serovar Enteritidis. Testing asymptomatic as well as symptomatic food handlers in outbreak investigations is imperative. Pre- and post-hiring screening might be considered as preventive measures; hygiene and sanitation education are essential.

Hereditary angioedema is a rare genetic disorder, manifested by recurrent edema leading to disfigurement, organ dysfunction and life-threatening respiratory impairment that may become fatal. The hallmark of HAE is a C1 esterase inhibitor deficiency, but recent evidence points at bradykinin as the main mediator that causes hyperpermeability of small vasculature, leading to accumulation of edema fluid. Current therapeutic options for HAE[1] are limited, and consist of drugs, replacement therapy, and supportive treatment. In view of many disadvantages of the current therapeutic modalities new approaches to the treatment of HAE are now being offered. This review summarizes our experience with a new line of medications developed for the treatment of acute exacerbations and prophylaxis of HAE – icatibant: bradykinin receptor antagonist, ecallantide: kallikrein inhibitor, and two C1 INH[2] preparations: Berinert-P, human plasma-derived concentrate, and Rhucin: novel recombinant C1-INH produced in transgenic rabbits. Preliminary results of these studies are encouraging and may bring new hope to the patients with this distressing condition. The exact number of HAE patients in Israel is unknown and because patients are treated individually and comprehensive laboratory assessment is partial, many cases might be missed or not treated according to accepted guidelines. We offer a new specialty center for HAE patients, addressing the medical and psychosocial needs of patients and their families.

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: 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: 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.