Israel Medical Association Journal

Background: Diabetes mellitus is associated with microvascular and macrovascular diseases, potentially manifested as endothelial dysfunction. In adults with type 2 diabetes the haptoglobin genotype 1-1 has been shown to have a protective role in inhibiting the development of complications. Although complications from type 1 diabetes are infrequent during childhood, endothelial dysfunction, which is an early marker of vascular complications, may occur.

Objectives: To evaluate endothelial function in adolescents with type 1 diabetes before the development of complications and to test for potential relationships between endothelial dysfunction and haptoglobin genotype.

Methods: The study group comprised 15 adolescents with type 1 diabetes. All underwent a general physical examination, diabetes control evaluation (including HbA1c levels), endothelial function assessment and haptoglobin genotype determination.

Results: There was a significant negative correlation between HbA1c levels and endothelial function (r = -0.48, P < 0.05), and HbA1c was significantly higher in patients with endothelial dysfunction than in those with normal endothelial function (9.9 ± 2.2 vs. 7.7 ± 1.0 mg/dl, P < 0.05). In addition, there was a tendency toward a positive correlation between high density lipoprotein and endothelial function (r = 0.4, P < 0.1). There was no correlation between the haptoglobin genotype and endothelial function.

Conclusions: These results show that even in patients without complications, uncontrolled type 1 diabetes is associated with endothelial dysfunction, which may lead to microvascular complications in the future.
 

Background: Seasickness is thought to result from conflicting inputs from the vestibular, visual and somatosensory systems. The otolithic organs, which are responsible for the sensation of linear acceleration and tilt, are important in the pathogenesis of seasickness. Vestibular evoked myogenic potentials test is an objective evaluation of saccular function.

Objective: To examine whether saccular function is related to the pathogenesis of seasickness.

Methods: VEMP1 was performed in 10 subjects susceptible to seasickness and in 14 non-susceptible subjects.

Results: Bilateral VEMP responses were obtained in 7 (50%) of the non-susceptible subjects and 1 (10%) of the susceptible subjects. No differences were found between the groups in P13 and N23 wave latencies, amplitudes, N13-P23 inter-peak latencies, and peak-to-peak asymmetry ratios. More subjects in the susceptible group had asymmetry ratios > 35%.   

Conclusions: The attenuated saccular response might be explained in the context of the neural-mismatch theory and/or the subjective vertical theory, as reflecting an adaptation effort to sea conditions. A larger study is necessary to determine whether a statistically significant difference in VEMP responses exists between seasickness-susceptible and non-susceptible subjects.
 

Background: A paradoxical secular trend of an increase in preterm births and a decrease in low birth weights has been reported in many developed countries over the last 25 years.

Objective: To determine if this trend is true for Israeli neonates, and to add new information on secular trends in crown-heel length and head circumference.

Methods: A hospital-based historic cohort design was used. Anthropometric data for 32,062 infants born at Rabin Medical Center in 1986–1987, 1994–1996, and 2003–2004 were collected from the hospital’s computerized registry and compared over time for absolute values and proportional trends.

Results: For the whole sample (gestational age 24–44 weeks) there was a significant increase in mean birth weight (by 41 g), crown-heel length (by 1.3 cm), and head circumference (by 0.1 cm) from 1986 to 2004 (P < 0.001). A similar trend was found on separate analysis of the post-term babies. Term infants showed an increase in mean length and head circumference (P < 0.001), but not weight, and moderately preterm infants (33–36 weeks) showed an increase in mean weight (81 g, P < 0.001) and mean length (1.0 cm, P < 0.001), but not head circumference. The proportion of post-term (42–44 weeks), preterm (24–36 weeks), very preterm (29–32 weeks), extremely preterm (24–28 weeks), low birth weight (< 2500 g) and very low birth weight (< 1500 g) infants decreased steadily and significantly over time (P < 0.002).

Conclusions: Babies born in our facility, term and preterm, are getting bigger and taller. This increase is apparently associated with a drop (not a rise) in the proportion of preterm infants. These results might reflect improvements in antenatal care and maternal determinants.
 

Background: Until three decades ago coronary heart disease and stroke were considered rare in the Israeli Bedouin population. Today, this population shows increasing high prevalence compared to the Jewish population.

Objectives: To evaluate the prevalence of diagnosed cardiovascular risk factors among the Bedouin (hypertension, diabetes mellitus, dyslipidemia), and to assess compliance with follow-up tests and drug treatment.

Methods: The study included all listed patients aged 20 years and older in eight clinics in major Bedouin towns, and in two large teaching clinics in Beer Sheva (Jewish population). Risk factor data were extracted from the clinics' computerized databases. For those diagnosed with hypertension, diabetes or dyslipidemia, drug purchasing data were collected from the pharmacy database to determine compliance with treatment, and from the central laboratory mainframe (HbA1c and low density lipoprotein-cholesterol) to evaluate follow-up and control.

Results: A significantly higher prevalence of diabetes in all age groups was found in the Bedouin population compared to the Jewish population; age-adjusted results show a prevalence of 12% vs. 8% respectively (P < 0.001). The prevalence of dyslipidemia and age-adjusted hypertension was lower among Bedouins (5.8% vs. 18.2%, P < 0.01 and 17% vs. 21%, P < 0.001 respectively). Two-thirds of hypertensive Bedouin patients and 72.9% of diabetic Bedouin patients were not compliant with treatment. For dyslipidemia only 10.4% of the Bedouins were compliant compared with 28.2% in the Jewish population (P < 0.001).

Conclusions: Compliance with drug therapy and follow-up tests was found to be a major problem in the Bedouin population.
 

Background: Age-related macular degeneration is the most common cause of legal blindness in the developed world including Israel. Ethnic background is a risk factor for advanced AMD[1] in several populations, however the relative prevalence of this disease in different ethnic groups in the Middle East is unknown.

Objectives: To compare the prevalence of advanced AMD in Arabs and Jews in Israel.

Methods: We performed a retrospective analysis of two independent groups of patients: the first group comprised a sequential series of Jerusalem residents who underwent photodynamic therapy for neovascular AMD (PDT[2] group), and the second group consisted of all individuals in Jerusalem who received a blind certificate due to AMD (legal blindness group). Control groups were assessed to exclude inherited ethnic associated bias in the two study groups.

Results: The PDT group included 146 patients: 142 were Jews (97.3%) and 4 were Arabs (2.7%). The legal blindness group included 340 Jerusalem residents: 326 Jews (96%) and 14 Arabs (4%). The number of Arab AMD patients in the two groups was lower than expected based on the ethnic composition of the age-matched Jerusalem population (P = 0.0002 for the PDT group, and P < 0.0001 for the legal blindness group). By contrast, the number of non-AMD Arab patients who were treated in the same clinic and the number of Arabs who received a blind certificate for diabetic retinopathy was not different from expected based on their relative number in the Jerusalem population.

Conclusions: Advanced AMD is less common in the Arab than the Jewish population of Jerusalem. Genetic and environmental factors may account for this difference. A population-based study is required to assess the overall prevalence of AMD in Jews and Arabs.

Background: Serology of amebiasis is affected by low sensitivity and specificity.

Objectives: To evaluate the advantage of the indirect hemagglutination assay and enzyme-linked immunosorbent assay in the diagnosis of amebiasis, using Entamoeba histolytica soluble antigen (macerated amebic antigens) prepared from four different virulent isolates, continuously cultivated in the presence of the original enteric bacteria.

Methods: Using IHA[1] and ELISA[2] with MAA[3] antigen we examined 147 sera samples from patients with gastrointestinal symptoms, and 11 sera from amebiasis cases (confirmed by microscopy and copro-antigen ELISA ).

Results: Of 104 of the 147 (70.7%) symptomatic cases that were amebiasis positive by IHA, 81 (55.1%) were positive by MAA-ELISA. In addition, of 11 amebiasis cases confirmed by microscopy and copro-antigen ELISA , 7 (64%) were amebiasis positive by both tests. Four species of bacteria were isolated from the ameba cultures: Escherichia coli, Morganella morganii, Proteus mirabilis, and Streptococcus lactis. Elimination of the bacteria from the cultures by an antibiotics cocktail containing gentamicin, imipenem, piperacillin-tazobactam and vancomycin was the preferred method. Absorption of patients' sera to bacterial antigen prior to serological analysis had only a marginal effect.

Conclusions: These results indicate a correlation of 61% between the ELISA developed in this study and the IHA tests in the diagnosis of amebiasis.

Background: In recent years there has been an increase in endovascular repair of thoracic aortic aneurysms. In cases of insufficient neck length, occlusion of left subclavian artery achieves proper sealing and is usually well tolerated. Selected cases require revascularization of the left subclavian artery, including patients after coronary bypass surgery (left internal mammary to left anterior descending) and those with arm claudication or subclavian steal syndrome.

Objectives: To evaluate the tolerability of left subclavian artery occlusion by stent graft without revascularization.

Methods: Thirty patients with thoracic aortic aneurysms underwent endovascular repair between July 2000 and November 2004. Eleven of them had occlusion of the left subclavian artery that required revascularization in two. Follow-up (average 3 years) included a) blood pressure measurements of both arms at rest, after effort and pulse palpation, and b) vertebral blood flow by duplex scan.

Results: Of nine patients with no revascularization, 8 (89%) tolerated left subclavian artery occlusion with no claudication or steal syndrome; one (11%) suffered mild claudication only after effort and required no intervention. No left radial pulses were palpated in the nine patients. Blood pressure measurements in the left arm showed an average decrease of 40%, which remained constant after induced effort in all patients and was clinically insignificant. Duplex scan demonstrated reverse flow in the left vertebral artery in 8 of 9 patients (89%) and occlusion in 1 (originating in the arch and covered by the stent graft) with no clinical symptoms.

Conclusions: Left subclavian artery occlusion by stent graft is a tolerable procedure in the long term. In most cases, the constant decrease in blood pressure remained unchanged during follow-up and had no significant adverse affects. Most patients do not require revascularization prior to the endovascular procedure.
 

Background: Depression is a leading cause of morbidity, disability and health care utilization. It is commonly encountered in primary care settings yet is often missed or suboptimally managed.

Objective: To summarize studies conducted in Israel on the prevalence of depression in primary care settings, its correlates, and predictors of treatment and outcome, and to discuss their implications for clinical practice and public health policy.

Methods: An electronic search was conducted using the MEDLINE and PsychINFO databases. The inclusion criteria were original studies that assessed aspects of depression in a population aged 18 or older, were conducted in primary care settings in Israel, and with sufficient detailed description of depression-related measures, study sample and outcome measures. Twelve articles reporting results from 7 studies met these criteria.

Results: The prevalence of current depression in primary care varied considerably across studies: 1.6–5.9% for major depression, 1.1–5.4% for minor depression, 14.3–24% for depressive symptoms. Depression was consistently related to female gender and few years of education, and was associated with disability, decreased quality of life, and increased health-related expenditure. Many cases of depression were undiagnosed and most patients had persistent depression or achieved only partial remission.

Conclusions: Depression represents a serious challenge for the primary health care system in Israel. Greater efforts should be focused on screening and treating depression in primary care. However, the studies reviewed here used different methodologies and assessed different aspects of depression, and, therefore, should be generalized cautiously. Systematic research on the prevalence, correlates and management of depression in primary care, with emphasis on collaborative care models, is strongly needed to inform research, clinicians and health care policy makers.

Background: Interleukin-8 is a prototypical inflammatory chemokine that induces leukocyte migration to inflammatory sites. Leukocyte recruitment in response to gradients of this chemokine is attenuated at advanced stages of inflammation to prevent damage to surrounding healthy tissues. Our published studies suggest that over-phosphorylation of focal adhesion kinase in migration-desensitizing conditions is involved in cessation of cell motility. This over-phosphorylation of FAK[1] was induced by IL-8[2] only when the receptor transmitting the chemokine signals was CXCR2, and not CXCR1, indicating that the two IL-8 receptors diverge in their signaling properties.

Objectives: To analyze the regulation of FAK in CXCR2-expressing hematopoietic cells under conditions of migratory desensitization, focusing on the roles played by adhesion-related components in this process.

Methods: Under conditions of migratory desensitization, we determined IL-8-induced cell spreading and FAK localization following disruption of actin filaments, and evaluated the role of integrins in FAK phosphorylation.

Results: The disturbance of intact activity of actin filaments resulted in inhibition of cell spreading and modification of FAK intracellular localization upon IL-8 stimulation. Also, adhesion-dependent pre-stimulation of integrins was required for IL-8-induced FAK phosphorylation.
Conclusions: Intact actin filaments and integrins are required for optimal IL-8-induced FAK phosphorylation in conditions of migratory desensitization. These observations suggest that lack of adequate activity/regulation of adhesion-related components may give rise to FAK activities that are not appropriately controlled, possibly leading to pathological conditions that are associated with perturbed leukocyte migration phenotypes

Background: The use of computed tomography in Israel has been growing rapidly during recent decades. The major drawback of this important technology is the exposure to ionizing radiation, especially among children, who have increased organ radiosensitivity and a long lifetime to potentially develop radiation-related cancer.

Objective: To estimate the number of excess lifetime cancer deaths related to annual CT scans performed in children in Israel.

Methods: We used CT scan utilization data from 1999 to 2003 obtained from the second largest health management organization in the country to project age and gender-specific CT scan use nationwide. Based on published organ doses for common CT examinations and radiation-related cancer mortality risk estimates from studies in survivors of the atomic bomb, we estimated the excess lifetime risks for cancer mortality attributed to use of CT in children and adolescents (up to 18 years old) in Israel.

Results: We estimated that 17,686 pediatric scans were conducted annually in Israel during 1999–2003. We project that 9.5 lifetime deaths would be associated with 1 year of pediatric CT scanning. This number represents an excess of 0.29% over the total number of patients who are eventually estimated to die from cancer in their lifetime.

Conclusions: Pediatric CT scans in Israel may result in a small but not negligible increased lifetime risk for cancer mortality. Because of the uncertainty regarding radiation effects at low doses, our estimates of CT-related cancer mortality should be considered with caution. Nevertheless, physicians, CT technologists, and health authorities should work together to minimize the radiation dose for children to as low as reasonably achievable and encourage responsible use of this essential diagnostic tool.
 

Background: The Fibrotest-Actitest™ is a six-parameter scoring system that allows quantification of liver fibrosis and inflammation. This test has been validated by several studies in hepatitis B and C viruses and alcoholic liver disease, with a high correlation between the liver biopsy and the results of the FT-AT[1] (AUROC between 0.78 and 0.95).The FT-AT was introduced in Israel (Rambam Laboratory) in March 2005.

Objectives: To assess the results of HCV[2] patients who underwent the test during the period March 2005 to February 2006.

Methods: Serum was taken and brought to the central laboratory performing the tests within 4 hours. Six parameters were evaluated using commercial kits approved by the designer of the test (Biopredictive): total bilirubin, gamma-glutamyltransferase, alpha-2 macroglobulin, haptoglobin, alanine aminotransferase, and apolipoprotein-A1. The results were sent to the website of Biopredictive (France), which provided the FT-AT score online using a patented formula.

Results: Of the 325 patients tested, only 4 were not interpretable because of hemolysis. Patients' age ranged from 7 to 72 years (median 42); 54% were female. Liver biopsy was performed in 81 patients and was compared with the results of the Fibrotest. Findings were as follows: 27% of the patients were F0, 19% F1, 20% F2, 17% F3 and 17% F4; 18% were A0, 32% A1, 28% A2 and 22% A3. The AUROC curve comparing the Fibrotest with liver biopsy with a cutoff point at F2 and A2 for significant fibrosis and inflammation was 0.85 and 0.79 respectively.

Conclusion: Fibrotest is a simple and effective method to assess liver fibrosis and inflammation and can be considered an alternative to liver biopsy in most patients with HCV.