Israel Medical Association Journal

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.

Background: Myeloperoxidase levels were shown to reflect endothelial dysfunction, inflammation, atherosclerosis and oxidative stress.

Objectives: To examine the role of circulating myeloperoxidase, a leukocyte-derived enzyme, as a predictor of mortality in patients with congestive heart failure.

Methods: Baseline serum MPO[1] levels were measured in 285 consecutive CHF[2] patients and 35 healthy volunteers. N-terminal pro-brain natriuretic peptide and high sensitivity C-reactive protein concentrations were also measured. The primary outcome endpoint was overall mortality.

Results: MPO levels were significantly elevated in patients with CHF compared to healthy volunteers (P = 0.01). During a mean follow-up of 40.9 ± 11.3 months there were 106 deaths. On a univariate Cox regression analysis MPO levels were of marginal value (P = 0.07) whereas NT-proBNP[3] was of considerable value (P < 0.0001) in predicting all-cause mortality. By dividing our cohort according to NT-proBNP levels into high, intermediate and low risk groups a clear difference in mortality was shown. By further dividing the patient cohort according to MPO levels above or below the median (122.5 ng/ml), mortality prediction improved in the patients with intermediate NT-proBNP values.

[1] MPO = myeloperoxidase

[2] CHF = congestive heart failure

[3] NT-proBNP = N-terminal pro-brain natriuretic peptide

Background: Infections with blood-borne viruses are a major health problem among illicit drug users. There is little information about infection rates and risk factors for hepatitis virus B, C or the human immunodeficiency virus in drug users in Israel.

Objectives: To determine the prevalence of HCV[1], HBV[2] and HIV[3] infections in a large cohort of drug users in Israel; to compare rates of HCV, HBV and HIV between injecting versus non-injecting drug users and between different origin countries; and to identify risk factors for HCV among illicit drug users.

Methods: We conducted a cross-sectional interviewer-administered questionnaire and serological screening for HCV, HBV and HIV in 1443 consecutive drug users diagnosed at the Israeli National Center for Diagnosis of Drug Addicts between January 2003 and December 2005.

Results: Fourteen (0.9%), 51 (3.5%) and 515 (35.7%) subjects tested positive for HIV, HBV and HCV, respectively. All three infections (HIV, HBV and HCV) were significantly more common among injecting drug users and immigrants from the former Soviet Union and other East European countries compared to native Israelis. Multivariate analysis showed that HCV infection was associated with age (> 40 years) (OR=2.06, 95% CI 1.40–3.03), immigration from East European countries and the former Soviet Union (OR=4.54, 95% CI 3.28–6.28), and injecting drug use (OR=16.44, 95% CI 10.79–25.05).

Conclusions: HIV, HBV and HCV prevalence among drug users in Israel is significantly lower than in North America and West Europe. Risk factors for HCV infection in this population include injecting drug use, older age, and immigration from the former Soviet Union.

Background: Clinicians’ impression of adolescents' alcohol or drug involvement may underestimate substance-related pathology.

Objectives: To describe the characteristics of adolescents presenting to the pediatric emergency department due to substance abuse and to determine whether physicians can reliably identify these patients.

Methods: We conducted a prospective cohort study of all patients aged 12–18 years presenting to a pediatric emergency department between 1 January 2005 and 31 December 2006 for whom a urine drug screen or ethanol blood levels was ordered. According to departmental protocol urine drug screen and ethanol levels are taken for specific indications. Based on the history and clinical findings the pediatrician in the ED[1] assessed on a 5-point likelihood scale the possibility that the patients’ symptoms were related to substance abuse.

Results: Of the 139 patients in the study group 40 (30%) tested positive for ethanol or drugs of abuse. The median age was 16. Compared with patients who tested negative, there were more patients with decreased level of consciousness among patients who tested positive for ethanol or drugs (5% vs. 33% respectively, P < 0.001). The median physician estimate for the likelihood of substance abuse was 5 in patients who tested positive and 2 in patients who tested negative (P < 0.001). The likelihood of a positive drug/ethanol test was not affected by age or gender.
Conclusions: Since the likelihood of substance abuse is higher in patients presenting with a low level of consciousness, physicians may accurately assess the likelihood of substance abuse in these patients

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: Erectile dysfunction is associated with treatable cardiovascular risk factors; therefore, screening for erectile dysfunction and its cardiovascular risk factors is of clinical importance.

Objectives: To detect erectile dysfunction cases and assess their severity among military personnel.

Methods: The Sexual Health Inventory for Men questionnaire was handed out to military personnel aged 25–55 years during routine examinations.

Results: A total of 19,131 men, with a mean age of 34.0 ± 7.1 years, participated in routine physical examinations during the years 2001–2005. More than half of them (n=9956, 52%) completed the SHIM[1] questionnaire. No significant differences were found between those who completed the SHIM questionnaire and those who did not, in terms of mean age, mean body mass index, and prevalence of cardiovascular risk factors. One out of every four men (25.2%) suffered from erectile dysfunction, which was mild in 18.9%, mild to moderate in 4.4%, moderate in 1.1% , and severe in 0.7%. Even though treatable cardiovascular risk factors were quite prevalent in the study group (45.2% of them suffered from dyslipidemia, 25.6% smoked, 4.2% suffered from essential hypertension, and 1.6% from diabetes mellitus), erectile dysfunction was significantly associated with age and diabetes mellitus alone (P < 0.0001).

Conclusions: There is a high prevalence of erectile dysfunction and associated treatable cardiovascular risk factors in Israeli men aged 25–55, especially those with diabetes. 

Background: With regard to ethnic predilections for Gaucher disease, the most common storage disorder, Ashkenazi Jews are at risk for the non-neuronopathic form (type I), Norbottnian Swedes are at risk for the sub-acute neuronopathic form (type III), and perhaps Arabs are at risk for the very rare cardiac variant of the sub-acute neuronopathic form (type IIIc) for which there is a relatively tight genotype-phenotype correlation. Type II, the acute infantile form, being the rarest form, has not been associated with any ethnic predilection.

Objectives: To examine whether Arab ethnicity influences the Gaucher phenotype.

Methods: We reviewed the records of all Arab patients in a referral clinic of 586 patients in Israel.

Results: There were 46 patients (7.8%) of Arab ethnicity: 23 (50%) had type I disease, 16 (34.8%) had type IIIc disease, 4 (8.7%) had type IIIb disease, and 3 (6.5%) had type II disease. Type IIIc disease was characterized by genotype-phenotype correlation with homozygosity for the D409H (1342C) mutation. All five Bedouin patients (10.9%) had the R48W (C259T) mutation on at least one allele.

Conclusions: For all genotypes, disease severity among Arab patients was relatively similar to that reported among other Caucasian patients. Apparently Arab ethnicity does not impact phenotypic expression in Gaucher disease in a unique manner. The predilection for type IIIc may be a result of consanguinity.
 

Background: A substantial number of premature deliveries occur in hospitals lacking neonatal intensive care facilities. We previously demonstrated a comparable outcome of very low birth weight infants delivered in a level II nursery to that of inborn infants delivered in our tertiary care center, but a similar comparison of extremely low birth weight infants has not been done.

Objectives: To compare the neonatal outcome (mortality, severe intraventricular hemorrhage/periventricular leukomalacia, bronchopulmonary dysplasia and intact survival) of inborn and outborn ELBW[1] infants, accounting for sociodemographic, obstetric and perinatal variables.

Methods: We compared 97 ELBW infants (birth weight ≤ 1000 g.) delivered between the years 2000 and 2004 in a hospital providing neonatal intensive care to 53 ELBW babies delivered in a referring hospital. A univariate model was first applied to examine the associations of the individual independent variables with the outcome variable, followed by a logistic stepwise regression analysis for each of the outcome variables. The odds ratios for each predictor were reported as well as their P values and 95% confidence intervals.

Results: In the stepwise logistic regression analysis, accounting for a possible confounding effect of the independent variables, ‘hospital of birth’ remained a statistically significant predictor in the final step only for mortality, with odds ratio (inborns relative to outborns) of 3.32 (95%CI[2] 1.19–9.28, P = 0.022). No statistically significant associations with the other outcome variables were found (severe IVH[3]/PVL[4] odds ratio = 1.99, 95%CI = 0.77–5.14, P = 0.155; BPD[5] odds ratio = 0.60, 95%CI = 0.19–1.91, P = 0.384; intact survival OR[6] = 0.56, 95%CI = 0.23–1.35, P = 0.195).

Since the beginning of medical history, ethics has interested medical practitioners. The subject has become particularly important in recent years due to the huge advancements in medicine and medical technology and has elicited much public interest. While international ethical principles and guidelines have been established, classical Jewish tradition has always placed great emphasis on bioethics. Prof. Avraham Steinberg’s monumental Encyclopedia of Jewish Medical Ethics presents the subject comprehensively and in depth. We propose a bioethics syllabus, to be integrated into the medical curriculum in three stages: i) preclinical – covering basic ethical concepts and principles, relevant history, and ethical codes; ii) clinical  – covering bioethical topics relating to the human life cycle; iii) prior to students' final examinations and further specialization – covering bioethical topics relating to their personal interests. Steinberg’s Encyclopedia is an ideal basis for the development of a professional course, including Jewish traditional aspects. Such a course would provide future physicians with a varied cultural and intercultural background, help shape their image, and improve the quality of medical care.

Background: Skin basal and squamous cell carcinomas together account for over half of all newly diagnosed cancer cases. Frozen  section control of surgical margins is often required in the head and neck region. A paraffin permanent section does not always confirm the results of a frozen section.

Objectives: To test the diagnostic accuracy of frozen section histopathological analysis in determining the free margins of excised tumors.

Methods: This was a retrospective study of 169 cutaneous basal and squamous cell carcinomas excised with surgical margins diagnosed by frozen section and confirmed by permanent paraffin sections. The data included patients' age, gender, clinical and histopathological diagnosis, as well as characteristics of the lesions.

Results: There were 149 (88%) basal cell carcinomas and 20 (12%) squamous cell carcinomas. False negative margins were found in 19 cases (11.2%) and false positive margins in 11 cases (6.6%). We did not find any correlation between false positive or false negative margins and patients' age, gender, tumor size, tumor location, or the presence of sun-damaged skin. A significantly lower rate of false negative results was found in the residual tumor group.

Conclusions: Our findings show support the use of frozen section margin control in selected patients suffering from non-melanoma skin cancer of the head and neck.
 

Background: Reports of burn injuries in children are usually made by highly specialized burn units. Our facility admits children with burns < 20% total body surface area, while those with major burns are transferred to burn units at tertiary care facilities.

Objectives: To review our experience with thermal burns.

Methods: We conducted a retrospective review of all thermal burns admitted to our hospital during a 5 year period.

Results: Among 266 patients (69.2% boys) aged 3.5 ± 3.6 years, children < 3 years old were the most frequently injured (64.7%). Scalds (71.4%) were the most common type of burn. Partial thickness burns were sustained by 96.6% of children and TBSA[1] burned was 4.2 ± 3.6%. The mean hospital stay was 3.8 ± 4.5 days, and was significantly prolonged in girls (4.6 ± 4.8 vs. 3.5 ± 4.3 days, P = 0.01). Percent TBSA burned was correlated with patient age (r = 0.12, P = 0.04) and length of hospital stay (r = 0.6, P < 0.0001). Six patients (2.3%) (mean age 3.4 ± 2.3 years) were hospitalized in the Pediatric Intensive Care Unit due to toxin-mediated illness.

Conclusions: Children under the age of 3 years are at increased risk for burn injury, but older children sustain more extensive injuries. Prevention and awareness are needed for child safety.

Background: Diseases causing increased pulmonary pressure will subsequently cause a dilation of the pulmonary arteries and right heart chambers.

Objectives: To assess the capability of computed tomography angiography and high resolution CT to diagnose and estimate the severity of pulmonary arterial hypertension as compared with standard means of right heart catheterization, echocardiography and pulmonary function tests.

Methods: The study included 38 patients with PHT[1] who underwent CT angiography and HRCT[2] as part of their routine evaluation. Diagnose included: primary PHT (n=20), Eisenmenger syndrome (n=6), scleroderma (n=3), thromboembolic disease (n=3), and others (n=6). Mean pulmonary artery pressure was 58 mmHg (range 39–92 mmHg) by catheterization and peak systolic pressure 79 mmHg (range 40–135) by echocardiography. Findings for the diameters of the main pulmonary artery and its main branches, the ascending aorta, the right atria and ventricle as well as the position of the interventricular septum were compared with 22 chest CT scans as compared to patients with no known clinical history of pulmonary hypertension, performed for other reasons (trauma, oncology follow-up) during the study period. Correlations were also calculated with recent right heart catheterization, echocardiography and pulmonary function tests of the study group.

Results: Mean main pulmonary artery diameter in the study group was 3.55 ± 0.66 cm, pulmonary artery/ascending aorta ratio 1.2 ± 0.29, right pulmonary artery 2.63 ± 0.49 cm, left pulmonary artery 2.57 ± 0.5 cm. All diameters were significantly different from the control group (P < 0.0001). Main and right pulmonary artery diameters correlated to the pressure measurement by echocardiography (P = 0.001). Bronchial collaterals were found in 11 patients (30%). The position of the interventricular septum correlated well with the echocardiography study.

Conclusions: The size of the main pulmonary artery on CT angiography has a good predictive value regarding the severity of PHT.