Israel Medical Association Journal

Background: The majority of human brucellosis cases in Israel are caused by the ingestion of unpasteurized dairy foods produced from unlicensed family-owned flocks whose products are sold door-to-door at low prices. Exposure to infected farm animals is another major cause of infection.

Objectives: To determine, by examining recent incidence data and brucellosis control programs, whether a reduction in the incidence of human brucellosis in Israel can be sustained.

Methods: Case information is reported to the Health Ministry and national data are compiled and analyzed by the Division of Epidemiology. The current study focuses on data from 1998 through 2009 and discusses several of the major prevention and health education programs that have been implemented.

Results: An incidence decline of almost 70% during the period 1998–2002 was followed by a return to previously existing levels, although the incidence has remained consistently lower than in past decades. The disease is mostly limited to certain sectors of the rural Arab population. In 2009 the incidence rate per 100,000 population was 7.0 among Arabs compared with 0.2 among Jews. Between 1998 and 2009, 63% of cases were from the Beer Sheva and Acre health districts, which together comprise 15.5% of the Israeli population. Control programs - including efforts to combat brucellosis in animals and to discourage the sale of unpasteurized homemade dairy products - have met with partial success.

Conclusions: Without routine vaccination of all family-owned flocks, more effective restraints on the market for unpasteurized dairy foods and improved regional cooperation, human brucellosis will continue to be a contained, but persistent, health problem in Israel due to cultural behavior, socioeconomic factors, and the regional political environment.
 

Background: Amyloidosis of familial Mediterranean fever (FMF) may lead to end-stage renal failure, culminating in kidney transplantation. Since amyloidosis is prompted by high serum amyloid A (SAA) levels, increased SAA is expected to persist after transplantation. However, no data are available to confirm such an assumption.

 Objectives: To determine SAA levels in kidney-transplanted FMF-amyloidosis patients and evaluate risk factors for the expected high SAA levels in this patient group.

Methods: SAA, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values were obtained from 16 kidney-transplanted FMF-amyloidosis patients, 18 FMF patients without amyloidosis and 20 kidney-transplanted patients with non-inflammatory underlying disease. Demographic, clinical and genetic risk factors evaluation was based on data extracted from files, interviews and examination of the patients.

Results: SAA level in FMF patients who underwent kidney transplantation due to amyloidosis was elevated with a mean of 21.1 ± 11.8 mg/L (normal ≤ 10 mg/L). It was comparable to that of transplanted patients with non-inflammatory disorders, but tended to be higher than in FMF patients without amyloidosis (7.38 ± 6.36, P = 0.08). Possible risk factors for the elevated SAA levels in kidney transplant patients that were excluded were ethnic origin, MEFV mutations, gender, age and disease duration.

Conclusions: Kidney-transplanted patients with FMF-amyloidosis and with other non-FMF causes displayed mildly elevated SAA levels, possibly resulting from exposure to foreign tissue rather than from various FMF-related factors. 

Background: Intravitreal injections of the anti-vascular endothelial growth factor (VEGF) drugs bevacizumab (Avastin®) and ranibizumab (Lucentis®) became the mainstay of treatment for various retinal pathologies, but there is no consensus among ophthalmologists on the precise use of these drugs.

Objectives: To describe the current application of anti-VEGF[1] drugs among retinal specialists in Israel.

Methods: A questionnaire was sent via email to all 62 members of the Israeli Society of Retinal Specialists. The survey included 34 questions on various aspects of the use of anti-VEGF drugs: diagnosis, treatment, follow-up of different retinal pathologies, and the measures taken for ensuring sterile administration of the intravitreal injections.

Results: Fifty members (80%) completed the survey. Most of them (56%) offered both bevacizumab and ranibizumab to their patients for age-related macular degeneration, but 70% were influenced by the patient’s socioeconomic status. Three consecutive monthly injections were usually recommended (58%) for the first 3 months, and treatment was extended as long as subretinal or intraretinal fluids persisted (57%). Over two-thirds (68%) switched the drugs after the 3-monthly series if the first one yielded no improvement in fluid status. The routine practice for intravitreal injection (> 80%) involved the wearing of sterile gloves, using an eyelid speculum, and administering povidone-iodine pretreatment and topical antibiotics after treatment.

Conclusions: Intravitreal VEGF administration varies widely among Israeli retinal specialists. The current survey is intended to assist Israeli ophthalmologists in establishing their own treatment strategy for patients with retinal pathologies.  

Background: Survival in T cell lymphoblastic lymphoma has improved over the past 30 years, largely due to treatment protocols derived from regimens designed for children with acute lymphoblastic leukemia.

Objectives: To assess the outcome of the NHL-BFM-95 protocol in children and adolescents hospitalized during the period 1999–2006.

Methods: We conducted a retrospective multi-institutional, non-randomized study of children and adolescents up to age 21 with T cell lymphoma admitted to pediatric departments in six hospitals in Israel, with regard to prevalence, clinical characteristics, pathological characteristics, prognostic factors, overall survival (OS) and event-free survival (EFS). All patients had a minimal follow-up of one year after diagnosis. The study was based on the NHL[1]-BFM[2]-95 protocol.

Results: At a median follow-up of 4 years (range 1–9 years), OS and EFS for all patients was 86.5% and 83.8%, respectively. OS was 86.7% and 83.3% for patients with stage III and stage IV, respectively, and EFS was 83.3% and 83.3%, respectively. EFS was 62.5% for Arab patients and 89.7% for Jewish patients (P = 0.014). Patients who did not express CD45 antigen showed superior survival (P = 0.028). Five (13.5%) patients relapsed, four of whom died of their disease. Death as a consequence of therapy toxicity was documented in one patient while on the re-induction protocol (protocol IIA).

Conclusions: Our study shows that OS and EFS for all patients was 86.5% and 83.8%, respectively.

Background: One of the major concerns in performing nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) is the risk of tumor recurrence.

Objectives: To assess the rate, predictors and mechanisms of oncological failure in patients after NSS[1] for renal cancer.

Methods: Between 1993 and 2008 NSS was performed in 229 patients via flank incision. Only patients without metastases at diagnosis and minimal 12 months follow-up were included in the outcome analysis.

Results: During a mean follow-up of 45 ± 34 months (range 6–168 months) tumor recurrence was observed in 13 patients (5.6%). Mean follow-up time for detection of oncological failure was 51 months (range 6–132 months).  All patients with oncological failure were males, with a mean age of 61 years (median 58, range 51–74 years). The average size of the enucleated lesion was 5 cm (range 4–7 cm). Intraoperative frozen sections as well as postoperative final pathological examination of the surgical margins were negative in all recurrent cases. Mechanisms of recurrence were distant metastases (n=4), surgical scar implantation (n=2), perirenal fat recurrence (n=2), local renal recurrence at the surgical site (n=1), and new renal lesions (n=4). Predictors of oncological failure included warm ischemia time (P = 0.058), tumor size (P = 0.001), tumor location (central versus peripheral) (P = 0.015), and multifocality (P = 0.001).

Conclusions: Distant dissemination, seeding during surgery, residual disease and new growth are the mechanisms responsible for cancer relapse. Large central lesions, long warm ischemia time and multifocality were significant predictors of oncological failure.

Background: Ulcerative colitis (UC) is a common and difficult-to-treat disease. In non-smokers the relative risk of developing UC[1] is 2.9 compared with smokers, who tend to have a later onset and a milder disease. Nicotine is the component of cigarette smoke responsible for the favorable effects in UC. Nicotine is metabolized by the enzyme CYP2A6. Subjects who are homozygotes for CYP2A6*4 gene polymorphism are poor nicotine metabolizers, while homozygotes for CYP2A6*1A polymorphism are extensive metabolizers.

Objectives: To compare the frequency of CYP2A6 and CHRNA3 polymorphisms among smokers and non-smokers with UC, and their effect on disease severity.

Methods: Data on the age at onset of disease, disease activity, and treatment were obtained from questionnaires completed by the 69 subjects in our study group. CYP2A6

*1A,*4A and CHRNA3 polymorphisms were determined by polymerase chain reaction and restriction enzyme analysis.

Results: Nine percent of the patients were current smokers, 30% were former smokers and 61% non-smokers. Among smokers and former smokers 63% were homozygotes for CYP2A6*1A and 4% were homozygotes for CYP2A6*4A, whereas among non-smokers 66% were homozygotes for CYP2A6*4A (P < 0.0001). There was no significant effect of CYP2A6 or CHRNA3 genotype on UC activity.

Conclusions: We found a very high proportion of poor nicotine metabolizers among non-smoking patients with UC and a very low proportion among current and former smokers, making it difficult to determine the effect of poor metabolizer genotype on disease activity in smokers with UC. However, it may be possible to identify UC patients who are poor metabolizers of nicotine and who may benefit from nicotine or nicotine-like pharmacological treatment.

Background: The rate of brain abnormalities in asymptomatic term neonates varies substantially in previous studies. Some of these rates may justify general screening of healthy newborns by head ultrasound.

Objectives: To assess the incidence of intracranial abnormalities among asymptomatic term newborns with HUS[1] and to detect high-risk populations that might need such screening.

Methods: This was a prospective study in 493 term newborns who underwent HUS and a neurological evaluation during the first 3 days of life. The neurological examination results were unknown to the sonographist and the examiner was blinded to the HUS findings. The abnormal HUS findings were classified as significant or non-significant according to the current literature.

Results: Abnormal HUS was found in 11.2% of the neonates. Significant findings were noted in 3.8% of the infants. There was no association between non-structural HUS findings (hemorrhage or echogenicity) and mode of delivery. There was no relationship between any HUS abnormality and birth weight, head circumference and maternal age, ethnicity, education or morbidity. The rate of abnormal neurological, hearing or vision evaluation in infants with a significant abnormal HUS (5.2%) was comparable to the rate in infants with normal or non-significant findings on HUS (3.1%).

Conclusions: There is no indication for routine HUS screening in apparently healthy term neonates due to the relatively low incidence of significant brain abnormalities in these infants in our population.

Background: Concomitant human immunodeficiency virus and human papillomavirus infection increases both HPV[1] persistence and the risk of invasive cervical cancer. An estimation of HPV prevalence among HIV[2]-positive women in Israel would contribute to improving care for this population and preventing morbidity and mortality related to cervical cancer.

Objectives: To determine the prevalence of HPV infection and cervical cytology abnormalities, and to assess the possible influence of HIV infection on HPV carriage in HIV-positive women attending the Infectious Disease Clinic at Soroka University Medical Center.

Methods: The study population included 84 HIV-seropositive women. They were examined by a gynecologist and screened for HPV genotyping, and Pap smears were obtained for cervical cytology. Demographic, behavioral, and HIV infection variables were also recorded and analyzed.

Results: Forty-nine (58.3%) of the study participants were HPV-positive; 34 of them had oncogenic genotypes. Young age (< 16 years) at first sexual intercourse was the only variable significantly associated with HPV infection (P < 0.05). Abnormal cervical cytology was present in 17 women (20.3%); 21 women were referred to colposcopy, which was abnormal in 9 (10.7%).

Conclusions: The prevalence of HPV carriage among HIV-positive woman in our study was slightly higher than published elsewhere. The prevalence of pathological cervical cytology was much higher than in the general population. An extremely high prevalence of pathological colposcopies requiring further treatment was found. Screening for HPV and premalignant changes in the uterine cervix is highly recommended in the HIV-seropositive population. We suggest that colposcopy be considered part of the routine workup in HIV-seropositive woman.

Background: The European Quality of Life 5-Dimensions questionnaire is one of the most commonly used measures of health-related quality of life.

Objectives: To present the feasibility, reliability, and validity of the Hebrew version of the EQ-5D[1].

Methods: We conducted face-to-face interviews with a representative sample (n=1666) of the Israeli Jewish population. The data collected included demographic and medical information, and self-valuation of health using the EQ-5D descriptive system, Visual Analogue Scale and Time Trade-Off. Construct validity was assessed by assuming that older individuals, those with a greater burden of diseases, and those reporting experience with their own severe illness would have lower EQ-5D indexes, VAS[2] and TTO[3] values. Test-retest reliability was assessed in a small sample (n=50) that was reevaluated after a 3 week interval.

Results: Test-retest reliability of the EQ-5D and VAS was very high (r ≥ 0.85). Reliability of the TTO was moderate (r = 0.48). There were significant differences in the EQ-5D index, profiles, VAS and TTO between healthy and sick respondents and younger and older respondents, indicating good validity of the instrument.

Conclusions: The Hebrew translation of the EQ-5D is a practical, reliable and valid instrument for assessing the health-related quality of life of the general Israeli Jewish population.

Background: The incidence of cutaneous leishmaniasis in northern Israel began to rise in 2000, peaking at 41.0 per 100,000 in the Kinneret subdistrict during the first half of 2003.

Objectives: To examine the morbidity rates of CL[1] in northern Israel during the period 1999–2003, which would indicate whether new endemic areas were emerging in this district, and to identify suspicious hosts.

Methods: The demographic and epidemiologic data for the reported cases (n=93) were analyzed using the GIS and SPSS software, including mapping habitats of suspicious hosts and localizing sites of infected sand flies.

Results: The maximal incidence rate in the district was found in the city Tiberias in 2003: 62.5/100,000 compared to 0–1.5/100,000 in other towns. The cases in Tiberias were centered on the peripheral line of two neighborhoods, close to the habitats of the rock hyraxes. Sand flies infected with Leishmania tropica were captured around the residence of those affected. Results of polymerase chain reaction were positive for Leishmania tropica in 14 of 15 tested patients.

Conclusions: A new endemic CL area has emerged in Tiberias. The most suspicious reservoir of the disease is the rock hyrax.

Background: Infiltrating ductal carcinoma and infiltrating lobular carcinoma account for more than 90% of all invasive breast cancer histological types. The rate of ILC[1] is reported to be increasing steadily in the United States and Europe.

Objectives: To describe the trend in the incidence of ILC in a large cohort of patients who underwent surgery in a single institution over an 18 year period.

Methods: Our comprehensive database of 2175 consecutive patients with invasive breast cancer diagnosed during the period 1992–2009 served for the analysis. Several potential factors associated with lobular carcinoma as compared with ductal carcinoma were evaluated.

Results: During this period, a 2.4-fold increase in the incidence of pure ILC was noted, from 4.6% in the years 1992–1994 to 10.9% in 2004–2006, followed by a modest decrease to 8.7% in 2007–2009. A significant association of lobular malignancies with external hormonal use was noted, including hormone replacement therapy exposure in patients diagnosed at age 50–64, and ovarian overstimulation during in vitro fertilization in those diagnosed at age 50 or less.  

Conclusions: Better diagnostic tools – such as the liberal use of ultrasound and magnetic resonance imaging – and more accurate pathological definition for ILC type appear to influence the changes in the incidence of ILC in the subgroups of invasive breast cancer.

Background: Professional volunteers play a crucial role in reinforcing emergency medical services in Israel. In order to encourage volunteers to return for additional shifts, the organization should provide conditions that will assure the return, particularly at a time of self-risk such as war. In 2009 Israeli emergency medical services (Magen David Adom) were required to increase preparedness in the southern part of the country due to missile attacks on civilian populations, while continuing their routine activities, i.e., responding promptly to emergency events. In order to perform these multiple functions, MDA[1] stations in the towns under attack were strengthened with volunteers from other regions of the country. These volunteers, trained as paramedics, served in 24–48 hour shifts.

Objectives: To identify the factors influencing the willingness of volunteers to return.

Methods: A questionnaire was used to assess the satisfaction of volunteers participating in the reinforcement with regard to their physical environment, job assignment and the actual activity they were involved in. Data were analyzed using SPSS statistical software.

Results: During the 10 days of the study, 121 volunteers reinforced southern MDA stations and 99 (81%) of them responded to the questionnaire. We found that volunteers' willingness to return to do more shifts was affected by their welcome and reception at the station, their job assignment, and their training and preparation for performing the necessary tasks. The sleeping conditions and the number of events they participated in were also contributing factors.

Conclusions: Factors that contribute to the willingness of volunteers to re-volunteer should be taken into account by organizations that rely on them.

Background: Enteral nutrition in the critically ill patient is often complicated by gastrointestinal intolerance, manifested by a large gastric residual volume. The frequency of GRV[1] assessment and the intolerant level above which feeding is stopped is controversial.

Objectives: To evaluate a novel approach to EN[2] by allowing high GRV and once-daily assessment that was correlated with the paracetamol absorption test.

Methods: We conducted a pilot prospective study in an 18 bed general intensive care unit. The study group comprised 52 consecutive critically ill mechanically ventilated patients. Enteral nutrition was started at full delivery rate. Once-daily assessment of GRV with three consecutively repeated threshold volumes of 500 ml was performed before stopping EN. The paracetamol absorption test was performed and correlated to GRV. Patients were divided into two groups: low GRV (< 500 ml), and high GRV (at least one measurement of GRV > 500 ml). Clinical outcome included maximal calories delivered, incidence of pneumonia, ICU[3] length of stay, and ICU and hospital mortality.

Results: There were 4 patients (9.5%) with ventilator-associated pneumonia in the low GRV group and 3 (30%) in the high GRV group (P = 0.12). GRV was inversely correlated to paracetamol absorption; however, neither GRV nor paracetamol absorption was associated with the development of pneumonia. Both groups had similar ICU length of stay (11.0 ± 8.2 vs. 13.8 ± 14.4 days, P = 0.41), and similar ICU (21% vs. 40%, P = 0.24) and hospital mortality (35% vs. 40%, P = 1.0).

Conclusions: In critically ill mechanically ventilated patients, allowing larger gastric residual volumes, measured once daily, enables enteral feeding with fewer interruptions which results in high calorie intake without significant complications or side effects.