Israel Medical Association Journal

Treatment of vasculitides has progressed markedly over the past few decades. Recent therapeutic strategies in severe and refractory anti-neutrophil cytoplasmic antibodies-associated vasculitides include immunomodulating methods (e.g., plasma exchanges), products (such as intravenous immunoglobulins) and, more recently, new agents called biotherapies. Some of them (e.g., anti-tumor necrosis factor-alpha and anti-CD20 monoclonal antibodies) have achieved promising results and are now often used to treat severe cases.

Background: In the course of occurrence of cerebral infarction, cerebral hemorrhage and subarachnoidal hemorrhage episodes, periodicities resembling those found in the solar and geomagnetic activity were found by Kováč and Mikulecký (2005).

Objectives: To investigate putative relationships between two indices of solar activity and one index of geomagnetic activity on one side and the occurrence of cerebral infarction on the other.

Methods: In addition to the 192 monthly cases out of 6100 new cases of cerebral infarction that occurred between January 1989 and December 2004, monthly averages for Wolf numbers, solar flares index and Ap index were included in the analysis. The cross-correlation between each cosmo-geophysical variable on the one hand and the number of new cases of the disease on the other was computed. The quadratic regression with the chosen time delay was also studied using, separately, the Wolf numbers, solar flares and Ap index as the explanatory variable and the number of cases of cerebral infarction as the responding variable.

Results: Significantly negative correlation coefficients between the monthly means of the Wolf numbers, of solar flares and of Ap index on the one hand and monthly numbers of new cases of the disease on the other were found for the delays between -6 and +17 months. The cross-regression results for the delay of +5 months (infarction delayed after each cosmo-geophysical variable by 5 months) displayed a linear decrease except for the Wolf numbers where the parabolic decrease of cases was significant.

Conclusions: An increased intensity of the studied cosmo-geophysical parameters appears to be significantly connected with decreased occurrence of cerebral infarctions, and vice versa. This effect seems to last up to 17 months. The results are supported by a few similar findings in the literature. Putative cosmo-biomedical connections warrant further study to verify them in larger samples and longer time scales. If confirmed, their mechanisms should be elucidated.
 

Background: Fanconi anemia complementation group C and Bloom syndrome, rare autosomal recessive disorders marked by chromosome instability, are especially prevalent in the Ashkenazi* Jewish community. A single predominant mutation for each has been reported in Ashkenazi Jews: c.711+4A→T (IVS4 +4 A→T) in FACC[1] and BLM^Ash in Bloom syndrome. Individuals affected by both syndromes are characterized by susceptibility for developing malignancies, and we questioned whether heterozygote carriers have a similarly increased risk.

Objectives: To estimate the cancer rate among FACC and BLM^Ash carriers and their families over three previous generations in unselected Ashkenazi Jewish individuals.

Methods: We studied 42 FACC carriers, 28 BLM^Ash carriers and 43 controls. The control subjects were Ashkenazi Jews participating in our prenatal genetic screening program who tested negative for FACC and BLM^Ash. All subjects filled out a questionnaire regarding their own and a three-generation family history of cancer. The prevalence rates of cancer among relatives of FACC, BLM^Ash and controls were computed and compared using the chi-square test.

Results: In 463 relatives of FACC carriers, 45 malignancies were reported (9.7%) including 10 breast (2.2%) and 13 colon cancers (2.8%). Among 326 relatives of BLM^Ash carriers there were 30 malignancies (9.2%) including 7 breast (2.1%) and 4 colon cancers (1.2%). Controls consisted of 503 family members with 63 reported malignancies (12.5%) including 11 breast (2.2%) and 11 colon cancers (2.2%).

Conclusions: We found no significantly increased prevalence of malignancies among carriers in at least three generations compared to the controls.

Background: Non-operative management of blunt splenic trauma is the preferred option in hemodynamically stable patients.

Objectives: To identify predictors for the successful non-operative management of patients with blunt splenic trauma.

Methods: The study group comprised consecutive patients admitted with the diagnosis of blunt splenic trauma to the Department of Surgery, Hadassah-Hebrew University Medical Center in Jerusalem over a 3 year period. Prospectively recorded were hemodynamic status, computed tomography grade of splenic tear, presence and extent of extra-abdominal injury, number of red blood cell units transfused, and outcome. Hemodynamic instability and the severity of associated injuries were used to determine the need for splenectomy. Hemodynamically stable patients without an indication for laparotomy were admitted to the Intensive Care Unit and monitored.

Results: There were 64 adults (45 males, mean age 30.2 years) who met the inclusion criteria. On univariate analysis the 13 patients (20.3%) who underwent immediate splenectomy were more likely to have lower admission systolic blood pressure (P = 0.001), Glasgow Coma Scale < 8 (P = 0.02), and injury to at least three extra-abdominal regions (P = 0.06). Nine of the 52 patients (17.3%) who were successfully treated non-operatively suffered from grade ≥4 splenic tear. Multivariate analysis identified admission systolic BP[1] (odds ratio 1.04) and associated injury to less than three extra-abdominal regions (OD[2] 8.03) as predictors for the success of non-operative management, while the need for blood transfusion was a strong predictor (OR 66.67) for splenectomy.

Conclusions: Admission systolic blood pressure and limited extra-abdominal injury can be used to identify patients with blunt splenic trauma who do not require splenectomy and can be safely monitored outside an ICU[3] environment. 

Background: Colonoscopy is the gold standard procedure for screening for colorectal cancer and surveillance after polypectomy or colorectal cancer surgery, for diagnosis in symptomatic patients and patients with fecal occult blood, and for screening in the high risk population. The adherence of referring physicians to the accepted recommendations can prevent long waiting lists for colonoscopy and save lives, costs and resources.

Objectives: To evaluate the knowledge of primary care physicians and gastroenterologists in Israel about current guidelines for colonoscopy screening and surveillance.

Methods: A 10-item questionnaire on proper follow-up colonoscopy for surveillance after polypectomy and screening for colorectal cancer in various clinical and epidemiological situations was administered to 100 expert gastroenterologists and 100 primary care physicians at a professional meeting. Answers were evaluated for each group of physicians and compared using the chi-square test.

Results: The compliance rate was 45% for the gastroenterologists and 80% for the primary care physicians. The rate of correct answers to the specific items ranged from 18.7% to 93.75% for the gastroenterologists and from 6.2% to 58.5% for the primary care physicians (P < 0.001 for almost every item).

Conclusions: The knowledge of physicians regarding the screening and surveillance of colorectal cancer needs to be improved.

Background: Common peroneal neuropathies, usually located at the fibular head, are one of the causes of drop foot, a condition often evaluated in the electromyography laboratory.

Objectives: To study the motor conduction properties of the common peroneal nerve and its branches of distribution in patients with paralyzed drop foot, several weeks after their first stroke, assuming that its inversion position can cause neuropathy around the fibular neck.

Methods: We performed peroneal nerve conduction study on 76 legs of 38 patients, 12–73 days after their first stroke. All the patients had flaccid drop foot on the involved side. The stimulating electrode was placed at the postero-lateral aspect of the fibular neck. Motor nerve conduction latency and compound muscle action potential amplitude were measured along the proximal part of the deep and the superficial peroneal nerve, comparing the paralyzed to the sound leg. Paired sample t-test and paired t-test were used to compare the nerve conduction properties between the sound and the paralytic leg. The linear liaison between the two legs was determined by Pearson coefficient and the test based on it.

Results: The differences between motor conduction latencies and between CMAP[1] amplitudes, comparing the paralyzed to the sound side, recorded in both the deep peroneal nerve and the superficial peroneal nerve, were statistically significant (P < 0.05).
Conclusions: It seems that the permanent equino-varus position of the paralyzed foot might affect common peroneal nerve conduction properties at the level of the fibular neck by demyelination, axonopathy, or both. Possible reasons for these pathological changes are nerve traction or nerve compression, but temperature changes in the paralytic leg should also be considered. Ankle-foot orthoses can be prescribed for prevention or correction of deformities of the foot and ankle and reduction of the weight-bearing forces

Background: Pulmonary tuberculosis continues to be a major cause of mortality, particularly in developing countries. Despite modern anti-TB[1] treatment, the elderly and immigrants from TB-endemic countries are at risk. Multidrug resistance has yet to be resolved..

Objectives: To determine the mortality rate and predictors of mortality among patients hospitalized with TB in Israel.

Methods: We evaluated the medical records of 461 patients with active pulmonary TB who were hospitalized in the department of respiratory care during the 5 year period 2000–2004. Data included demographic, clinical, laboratory and radiological findings, drug resistance as well as adverse reactions to anti-TB treatment.

Results:| Three main ethno-geographic groups were observed: 253 patients from the former USSR, 130 from Ethiopia, and 54 of Israeli origin (as well as 24 residents of other countries). Of the 461 patients 65 patients (13%) died in hospital. The factors that were best predictors of mortality were older age, ischemic heart disease, cachexia, prior corticosteroid treatment, hypoalbuminemia and pleural effusion (P < 0.005 for all). The ethno-geographic factor and the presence of multidrug-resistant bacteria had no significant effect on mortality in our study group.

Conclusions: The mortality rate in our study was relatively low, and there was no significant difference between the three ethno-geographic groups.

Background: The prevalence of obesity among children and adolescents in the western world has increased dramatically.

Objective: To assess the efficiency of routine childhood obesity screening by primary physicians in the pediatric population in Israel and the utilization of health services by overweight children.

Methods: The electronic medical records of children aged 60–83 months registered in 39 pediatric primary care centers between January 2001 and October 2004 (n=21,799) were reviewed. Those in whom height and weight were documented during a clinic visit (index visit) were classified as overweight, at risk of overweight, and normal weight by body mass index percentiles. The number of visits to the pediatrician, laboratory tests and health care costs 12 months after the index visit were calculated.

Results: Anthropomorphic measurements were performed in 1556 of the 15,364 children (10.1%) who visited the clinic during the study period. Of these, 398 (25.6%) were overweight, 185 (11.9%) were at risk of overweight, and 973 (62.5%) were normal weight. Children in the first two groups visited the clinic slightly more often than the third group, but the differences was not statistically significant (P = 0.12), and had significantly more laboratory tests than the rest of the children visiting the clinics (P = 0.053). Health care costs were 6.6% higher for the overweight than the normal-weight children.

Conclusions: Electronic medical records are a useful tool for population-based health care assessments. Current screening for obesity in children during routine care in Israel is insufficient and additional education of community pediatricians in diagnosis and intervention is urgently needed.

Background: Peritoneal carcinomatosis is an advanced form of cancer with poor prognosis that in the past was treated mainly palliatively. Today, the definitive approach to peritoneal surface malignancy involves peritonectomy, visceral resection and perioperative intra-abdominal hyperthermic chemotherapy. The anticipated results range from at least palliative to as far as intent to cure. Proper patient selection is mandatory.

Objectives: To determine whether cytoreductive surgery and intraperitoneal hyperthermic chemotherapy can extend survival, and with minor complications only, in patients with peritoneal carcinomatosis.

Methods: Twenty-two IPHP[1] procedures were performed in 17 patients with peritoneal carcinomatosis in our institution between 1998 and 2007: 6 had pseudomyxoma peritonei, 5 had colorectal carcinoma, 3 had ovarian cancer and 3 had mesotheliomas. All patients underwent cytoreductive surgery, leaving only residual metastasis < 1 cm in size. Intraperitoneal chemotherapy was administered through four large catheters (2F) using a closed system of two pumps, a heat exchanger and two filters. After the patient’s abdominal temperature reached 41°C, 30–60 mg mitomycin C was circulated intraperitoneally for 1 hour.

Results: The patients had a variety of anastomoses. None demonstrated anastomotic leak and none experienced major complications. Six patients had minor complications (pleural effusion, leukopenia, fever, prolonged paralytic ileus, sepsis), two of which may be attributed to chemotherapy toxicity (leukopenia). There was no perioperative mortality. Some patients have survived more than 5 years.

Conclusions: IPHP is a safe treatment modality for patients with peritoneal carcinomatosis. It has an acceptable complications rate and ensures a marked improvement in survival and in the quality of life in selected patients.

Background: Germline mutations in BRCA1 and BRCA2 genes account for only 20–40% of familial breast cancer cases. The CHEK2 gene encodes a checkpoint kinase, involved in response to DNA damage, and hence is a candidate gene for breast cancer susceptibility. Indeed, the CHEK2*1100delC truncating mutation was reported in a subset of mostly North European breast cancer families. The rate of the CHEK2*1100delC variant in the Ashkenazi* Jewish population was reported to be 0.3%.

Objectives: To evaluate whether CHEK2 germline mutations contribute to a breast cancer predisposition in Ashkenazi-Jewish high risk families.

Methods: High risk Ashkenazi Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1/BRCA2, were genotyped for germline mutations in the CHEK2 gene by exon-specific polymerase chain reaction followed by denaturing gradient gel electrophoresis and sequencing of abnormally migrating fragments.

Results: Overall, 172 high risk women were genotyped: 75 (43.6%) with breast cancer (average age at diagnosis 49.6 ± 9.6 years, mean ± SD) and 97 asymptomatic individuals (age at counseling 48.3 ± 8.2 years). No truncating mutations were noted and four previously described missense mutations were detected (R3W 1.2%, I157T 1.2%, R180C 0.6% and S428F 5%), one silent polymorphism (E84E 20.5%) and one novel missense mutation (Y424H 1.2%). Segregation analysis of the I157T and S428F mutations (shown to affect protein function) with the cancer phenotype showed concordance for the CHK2*I157T mutation, as did two of three families with the CHK2*S428F mutation.

Conclusions: CHEK2 missense mutations may contribute to breast cancer susceptibility in Ashkenazi Jews.

Background: Chronic obstructive pulmonary disease is an increasing cause of chronic morbidity and mortality around the world. The major cause of the disease is smoking. Despite the gravity of the problem there is no knowledge of its rate in the Israeli smoking population.

Objectives: To assess the prevalence of COPD[1]and early lung cancer among smokers.

Methods: People aged 45 up to 75 with a history of at least 20 pack-years cigarette smoking, including quitters, were screened for COPD. They were interviewed and a spirometry was performed.

Results: Of the 1150 people recruited 92% underwent and performed acceptable spirometry; 22% of these subjects had airflow limitation and were diagnosed with COPD according to the GOLD classification. Only 4% had been diagnosed as COPD prior to this screening. The majority of those tested were unaware of or unconcerned about developing the disease. There was no correlation between pack-years smoking and development of COPD, but there was a relative correlation of pack-years smoking and severity of COPD, particularly in the older group only (r = 0.42).

Conclusions: About one-fifth of the smokers aged 45 and up developed COPD. There is a significant gap between the disease distribution and its awareness in the population at risk. The need for a national screening program and early diagnosis of COPD in people at risk is needed.

Background: In an era of increasing antimicrobial resistance, knowledge of local antimicrobial susceptibility patterns of common uropathogens is essential for prudent empiric therapy of community-acquired urinary tract infections.

Objectives: To define antimicrobial susceptibility of Gram-negative uropathogens in northern Israel over a 10 year period and to compare it with antibiotic-use patterns in the same community.

Methods: We tested the susceptibility of all Gram-negative urinary isolates from outpatients at HaEmek Medical Center over the years 1995, 1999, 2002 and 2005 to common antimicrobial agents. MIC₉₀ of Escherichia coli to some of these agents was determined and antibiotic consumption data over the years 2000–2005 (DDD/1000/day) were obtained.

Results: We observed a rise in susceptibility rates of E. coli to amoxicillin-clavulanate, trimethoprim-sulfamethoxazole and nitrofurantoin and of other Gram-negative isolates to amoxicillin-clavulanate, ceftriaxone and cephalothin. Susceptibility rates of all Gram-negative uropathogens to ciprofloxacin decreased significantly. MIC₉₀ of E. coli for all drugs tested remained stable. There was a significant decrease in the use nitrofurantoin and TMP-SMX[1] and a significant increase in the use of ampicillin, cephalothin and ceftriaxone.

Conclusions: Antibiotic resistance patterns mostly remained unchanged or improved slightly. There was, however, a constant decrease in susceptibility of all Gram-negative uropathogens to ciprofloxacin. Antibiotic use patterns could not explain the changes seen in antibiotic susceptibility patterns.