Israel Medical Association Journal

Background: Kikuchi-Fujimoto disease is a benign and self-limited disease, first reported in Japan in 1972. The characteristic features of this disorder include lymphadenopathy and fever.

Objectives: To summarize our experience with Kikuchi disease with regard to clinical manifestations and outcome.

Methods: The patients included in the study were those diagnosed with Kikuchi disease during the years 2005–2008 in two departments of internal medicine at Sheba Medical Center.

Results: We identified five patients with Kikuchi disease; four of them were women and the mean age was 22.6 years. All the patients had cervical lymphadenopathy; three had other sites of lymphadenopathy. Four of the patients had fever higher than 39ºC. Two of them had splenomegaly and three reported weight loss. Three of the five patients experienced a relapse of the disease and were treated with steroids or non-steroidal anti-inflammatory agents. The diagnosis was confirmed in all the patients by an excisional biopsy of lymph node.

Conclusions: Kikuchi disease must be considered in every young patient with fever and lymphadenopathy. The disease usually has a benign course.

Background: While the burden of rotavirus infection with regard to hospitalizations has been extensively investigated, there are sparse data regarding the impact and the cost of this infection on the ambulatory part of the health system in Israel.

Objectives: To investigate the burden of rotavirus infection on the ambulatory system in Israel.

Methods: Infants younger than 3 years old examined for acute gastrointestinal symptoms in four pediatric clinics had their stool tested for rotavirus. The parents were contacted 7–10 days later and questioned about the symptoms of illness, medications given, use of diapers, consumption of formula, and any loss of parents' workdays.

Results: Rotavirus was detected in 71 of the 145 stool samples tested (49%). A total of 51 parents responded to the telephonic survey. Patients' mean age was 15.4 months. Three patients were hospitalized due to the illness. The mean duration of fever was 1.7 days. Infants with rotavirus gastroenteritis had on average 2.25 days of vomiting and 7.5 days of diarrhea. The average number of workdays lost was 2.65 days per RVGE[1] case. The cost of the average case of RVGE in Israel is 257 euros; 69.64% of this cost (179 euros) is due to parental work loss.

Conclusions: Our results indicate that the economic impact of the ambulatory cases in Israel is quite significant.

Background: Double balloon enteroscopy is a new technique that enables deep intubation of the endoscope into the small bowel lumen. Through a channel in the endoscope, invasive procedures such as biopsy, polypectomy and hemostasis can be performed, avoiding the need for surgery.

Objectives: To prospectively analyze our results of the first 124 DBEs[1] performed since February 2007.

Methods: The study group comprised all patients who underwent DBE at the Sheba Medical Center between February 2007 and February 2009. Recorded were the patients' demographic data, comorbidities, indications for the examination, results of previous non-invasive small bowel imaging (computed tomography enterography, capsule endoscopy, etc), investigation time, and results of the procedure including findings, endoscopic interventions, complications and pathological report.

Results: A total of 124 procedures were performed in 109 patients. Of the 124 examinations, 57 (46%) were normal and 67 (54%) showed pathology. The main pathologies detected on DBE were polyps (14%), vascular lesions (17.6%) and inflammation (12%). Endoscopic biopsies and therapeutic interventions were required in 58 examinations (46%). A new diagnosis was established in 15% of patients, diagnosis was confirmed in 29% and excluded or corrected in 12%. One complication was observed: a post-polypectomy syndrome that was treated conservatively.

Conclusions: DBE is a safe procedure and has a high diagnostic and therapeutic yield. Most of the examinations were performed under conscious sedation, and only a minority of patients required deeper sedation. 

Background: The forced oscillation technique is a non-invasive and effort-independent technique and is well suited for lung function measurement in young children. FOT[1] employs small-amplitude pressure oscillations superimposed on normal breathing. Therefore, it has the advantage over conventional lung function techniques in that it does not require patient cooperation for conducting respiratory maneuvers.

Objectives: To test the feasibility of the FOT test in preschool children and to compare the results to the commonly used spirometry before and after the administration of bronchodilator therapy.

Methods: Forty-six children (median age 4.9 years, range 1.8–18.3) attending the Pulmonary Clinic at Schneider Children's Medical Center tried to perform FOT and routine spirometry. Results were retrospectively analyzed. 

Results: Of the 46 children 40 succeeded in performing FOT and only 29 succeeded in performing simple spirometry. All but one of the 32 children aged 4 years and above (97%) could perform both tests. Nine of 14 children (64%) aged 4 and less could perform the FOT but only 3 (21%) could perform spirometry. Baseline values of respiratory resistance measured at 6 Hz (R6) negatively correlated with body length (r² = 0.68, P < 0.005). Twenty-four children performed both tests before and after bronchodilator therapy. A significant concordance was found between the measured responses to bronchodilators by FOT and spirometry (P < 0.01). Only one child had a negative response by FOT but a positive response by spirometry.

Conclusions: The FOT is a simple, non-invasive technique that does not require subject cooperation and thus can be utilized for measuring lung function in children as young as 2 years of age. Furthermore, the FOT was shown to reliably measure response to bronchodilator therapy.

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: The global spread of tuberculosis necessitates the development of an effective vaccine and new treatment modalities. That requires a better understanding of the differences in regulation of the immune responses to Mycobacterium tuberculosis between individuals who are susceptible or resistant to the infection. Previous immune studies in young Ethiopian immigrants to Israel did not demonstrate anergy to purified protein derivative or a Th2-like cytokine profile.

Objectives: To evaluate the profile of Th1 and Th2 cytokine production in immigrant TB patients, in comparison with asymptomatic control subjects.

Methods: The present study included (part 1): 39 patients with acute TB[1] (group 1), 34 patients with chronic relapsing TB (group 2), 39 Mantoux-positive asymptomatic TB contacts (group 3), and 21 Mantoux-negative asymptomatic controls (group 4). Patients were mainly immigrants from Eastern Europe and Ethiopia. Levels of interferon gamma, interleukin 2 receptor, IL-6[2] and IL-10 were measured in serum and in non-stimulated and PPD[3]-stimulated peripheral blood mononuclear cell culture supernatants, using commercial ELISA kits. In addition (part 2), levels of IFNg[4] and IL-12p40 were evaluated in 31 immigrant Ethiopian patients and 58 contact family members.

Results: Patients with acute disease tended to secrete more cytokines than contacts, and contacts more than chronic patients and controls, without a specific bias. None of the patients showed in vitro anergy. Discriminant probability analysis showed that from the total of 12 available parameters, a cluster of 6 (IFNg-SER[5], IFNg-PPD, IL-2R[6]-SER, IL-10-SER, IL-10-NS[7] and IL-6-PPD) predicted an 84% probability to become a TB contact upon exposure, 71% a chronic TB patient and 61% an acute TB patient. Family-specific patterns of IFNg were demonstrated in the second part of the study.

Conclusions: Firstly, no deficiency in cytokine production was demonstrated in TB patients. Secondly, acute TB patients secreted more cytokines than contacts, and contacts more than unexposed controls. Thus, neither anergy nor a cytokine dysregulation explains susceptibility to acute TB disease in our cohort, although chronic TB patients produced less cytokines than did acute patients and less than asymptomatic contacts. Thirdly, a certain cytokine configuration may predict a trend of susceptibility to acquire, or not acquire, clinical TB. It is presently unclear whether this finding may explain the disease spread in large populations. Finally, the familial association of IFNg secretion levels probably points towards a genetic regulation of the immune response to Mycobacterium tuberculosis. 

Background: Oral lichen planus is a cell-mediated immune condition of unknown etiology. A possible association of OLP[1] with hepatitis C virus infection has been documented in specific populations. However, no such possible association has been studied in Israel.

Objectives: To assess the prevalence of HCV[2] antibodies among patients with OLP in Israel.

Methods: The prevalence of HCV seropositivity was studied in OLP patients (n=62) and compared with that of a control group (n=65) and with the prevalence among healthy volunteer blood donors (n=225,452) as representatives of the general population.

Results: The prevalence of HCV, as detected by the presence of anti-HCV antibodies screened by enzyme-linked immunosorbent assay, and confirmed by recombinant immunoblot assay, was 4.8%, 1.5% and 0.1%, respectively. HCV seropositivity in the OLP patients was significantly higher than in the healthy blood donors (P < 0.001).

Conclusions: A possible association between OLP and HCV is suggested. Therefore, screening OLP patients for antibodies to HCV is recommended.

Background: The use of the bilateral internal mammary arteries has been reserved mainly for younger and low risk patients.

Aim: To assess the safety and efficacy of BIMA[1] grafting in older patients (≥ 70 years).

Methods: We reviewed the records of all consecutive patients ≥ 70 years old who underwent coronary artery bypass surgery with a BIMA graft in our institute over a 2 year period. Demographic data, operative data, perioperative morbidity and mortality were recorded. Findings were compared with a matched-size group of patients who underwent CABG[2] with a left internal mammary artery graft to left anterior descending artery.

Results: The study sample included 136 patients, of whom 68 underwent BIMA grafting and 68 LIMA[3] grafting. Baseline demographic and clinical characteristics were similar in the two groups. There was no significant difference in operative mortality between the BIMA and LIMA groups (1.5% vs. 0%, P = 0.3) or in mortality during follow-up at a mean of 16 months (4.4% vs. 2.9%, P = 0.4, respectively). There was no difference between the groups in the incidence of perioperative complications, re-admission and re-intervention rates during follow-up. Significant between-group differences were noted for mean cardiopulmonary bypass time (93.2 ± 34.7 BIMA vs. 108.8 ± 40.7 LIMA min, P = 0.02) and for red blood cell transfusion (1.9 ± 1.9 vs. 4.3 ± 2.8 packed cells/patient, P < 0.001).

Conclusions: The performance of mainly arterial revascularization with BIMA grafting in patients 70 years or older is as safe as LIMA grafting, with the added advantage of being a better conduit than saphenous vein graft, requiring fewer blood transfusions, and shorter cardiopulmonary bypass time.

Background: The etiology of chest pain with normal epicardial coronary arteries (cardiac syndrome X) seems to be related to endothelial cell dysfunction. Multiple factors are implicated in the pathophysiology, including evelated levels of homocysteine in the blood. Mutations in the MTHFR gene are associated with evelated levels of homocysteine.

Objectives: To test whether abnormal homocysteine metabolism is associated with syndrome X.

Methods: Forty-two women with chest pain, positive stress test and normal coronary arteries (syndrome X) and 100 asymptomatic women (controls) were studied for the C677T mutation. Vitamin B12, folic acid, and plasma levels of homocysteine were also measured. Endothelial cell function was studied in 10 patients with syndrome X and homozygosity for C677T mutation, and in 10 matched healthy controls. Folic acid (5 mg daily) was prescribed to syndrome X patients after initial measurements of ECF[1]. Following 13 weeks of treatment, ECF and blood tests were repeated and compared to baseline measurements.

Results: Homozygosity for C677T mutation was doubled in syndrome X vs. control (33%, 14/42 vs. 16%, 16/100, P < 0.02), and homocysteine levels were increased (9.16 ± 2.4 vs. 8.06 ± 2.6 μmol/L, P = 0.02). In the 10 homozygous patients, homocysteine levels decreased significantly after treatment with 5 mg/day folic acid (10 ± 3.3 vs. 5.4 ± 1.1 µmol/L, P = 0.004). Abnormal baseline ECF improved after treatment with folic acid: flow-mediated dilatation was greater (11.3 ± 7.9% vs. 0.7 ± 4.5%, P < 0.002), as was nitroglycerin-mediated dilatation (15.2 ± 9.0% vs. 5.6 ± 6.4%, P < 0.003). Frequency of chest pain episodes was significantly reduced after 13 weeks of folic acid treatment.

Conclusion: Our findings establish the association between the C677T mutation, endothelial cell dysfunction and cardiac syndrome X, and provide a novel and simple therapy for a subset of patients with syndrome X and homozygosity for the C677T mutation.