Israel Medical Association Journal

Objectives: To determine the properties of HAM as an antigenic substrate for the detection of autoantibodies in pemphigus vulgaris and bullous pemphigoid.

Methods: Immunomapping and tandem liquid chromatography mass spectrometry were used to delineate the antigenic structure of HAM in 25 pemphigus patients, 41 pemphigoid patients, and 36 controls. Immunoblotting and indirect immunofluorescence were used to study the diagnostic utility of HAM, and the results were compared to those of indirect immunofluorescence on monkey esophagus, immunoblotting using normal human skin, and enzyme-linked immunosorbent assay (ELISA).

Results: Immunomapping demonstrated the presence of all the antigens known to be targeted in autoimmune bullous skin diseases, in both normal human skin and HAM, except for the absence of BP230, and low threshold levels of Dsg1, Dsg3 and Dsc3 in HAM. HAM indirect immunofluorescence demonstrated anti-basement membrane zone antibodies in 48.7% of the pemphigoid patients, and anti-intercellular space antibodies in 72.0% of the pemphigus patients. HAM immunoblotting did not demonstrate anti-BP230 antibodies, but detected anti-BP180 antibodies in 53.6% of the pemphigoid patients. It did not demonstrate anti-Dsg1 and/or anti-Dsg3 antibodies in any of the pemphigus patients. These results were inferior to those of ELISA and monkey esophagus indirect immunofluorescence.

Conclusions: Compared to other studied methods, HAM does not offer advantages in detecting autoantibodies in bullous pemphigoid and pemphigus vulgaris. 

Objectives: To investigate whether the change in protocols over the years resulted in an outcome difference at two hospitals in Israel.

Methods: We thoroughly reviewed the records of 153 patients from Sheba Medical Center and Soroka Medical Center, of whom 106 comprised the study group. The patients were divided into two groups according to the treatment protocol used: 40 patients with the 1989/93 protocol and 66 with the 1999/2003 protocol. Outcome was analyzed for the two groups.

Results: We found a significant difference in disease-free survival (DFS) between the two groups for B cell-ALL (B-ALL) patients who achieved complete remission after induction. There was no difference in overall survival. We did not find any difference in outcome for T cell-ALL patients or for CD20-positive patients.

Conclusions: In our retrospective analysis, GMALL 99/2003 led to a better DFS for B-ALL patients who were in complete remission after induction. This is possibly related to the differences in medications between the protocols, but may also be due to better supportive care. Despite the proven advantage of the newer protocols regarding overall survival, in our experience there was no other significant difference between the two regimens. 

Objectives: To examine the proliferative index, as expressed by Ki67, in various subtypes of basal cell carcinoma, and to assess its relationship to various histological and clinical variables.

Methods: In this retrospective study 51 lesions of BCC were examined. In each case, the following data were gathered: demographic (age and gender), anatomic location, size of the lesion, and clinical follow-up.  Each case was stained immunohistochemically with anti-Ki67 antigen (MIB-1), and the proliferative index was determined. Histologic analysis was performed for the following data: presence of an ulcer, intensity of inflammatory infiltrate, histologic subtype, mitotic count, and the presence of perineural invasion.

Results: Basal cell carcinoma exhibited a wide variation of proliferative indices, ranging from 1% to 61%. A significant statistical correlation was observed between the proliferative index and the mitotic activity, tumor ulceration and brisk tumor-infiltrating lymphocytes.

Conclusions: The wide variation in the degree of proliferation (from almost no activity to highly proliferative tumors) suggests that basal cell carcinoma exhibits a wide spectrum of biological characteristics. Ulcerated lesions were characterized by high proliferative index. No true correlation was demonstrated between the proliferative index and the aggressive histologic subtypes, implying that other factors were more biologically significant. The degree of proliferation also showed significant statistical correlation with the degree of tumor infiltration by lymphocytes. The significance of this proliferation-associated increased immunogenicity needs to be further studied.

Objectives: To examine the effect of meloxicam, a selective COX-2 inhibitor, or low dose aspirin on the development of experimental atherosclerosis in apoE knockout (KO) compared to wild-type (WT) mice. We aimed to test the hypothesis that meloxicam, a potential vasculitis inducer, would exacerbate atherosclerotic lesions while aspirin, which is known to reduce the incidence of thrombosis occlusive events, would increase protection in this model.

Methods: We randomly divided 36 male apoE KO and 36 WT mice, 8 weeks old. Mice were treated for 10 weeks with 0.1 mg/ml aspirin, or 0.05 mg/ml meloxicam, dissolved in their drinking water. Control groups received regular drinking water. At sacrifice, the hearts were removed for histochemical staining and plaque size and composition were examined.

Results: Aspirin-treated animals displayed a decreased atherosclerotic lesion area compared to the untreated control mice, while meloxicam had a null effect on the extent of atherosclerosis in Apo E KO mice.

Conclusions: These results suggest that low dose aspirin reduces early atherosclerosis, while inhibition of COX-2 by meloxicam is not associated with an increase in atherosclerotic plaque size in this mouse model.

Objectives: To evaluate the predictive value of V/Q scanning in patients with impaired renal function.

Methods: We assessed all patients with impaired renal function who underwent V/Q scanning. The patients studied included those who also had CTPA (group 1) and those who did not (group 2). We recorded the results of V/Q scanning, chest X-rays, CTPA, D-dimer levels, ultrasound of deep veins, and clinical probability for PE (Wells' score) in group 1. CTPA results were considered true results. Anticoagulant treatment was documented in all the patients.

Results: Of the 45 patients in group 1, 12 (22%) had positive CTPA for PE. The positive predictive value (PPV) for patients with high probability results on V/Q scanning for PE was 30%. Restricting results to D-dimer levels ≥ 1000 ng/ml added little to this value. Restricting results to Wells’ score ≥ 7 resulted in 72% PPV. The negative predictive values for low or moderate probability were ~79 % and ~67% respectively. Of the 95 patients in group 2, all those with high probability for PE were treated with anticoagulants.

Conclusions: Patients with impaired renal function and high probability for PE on V/Q scanning had very low PPV for PE. Due to the lack of CTPA studies, patients with high probability for PE on V/Q scanning were treated with anticoagulants.

Objectives: To assess the role of electrocardiography-gated CT-angiography (ECG-CTA) in the routine evaluation of CHD in neonates and infants particularly for the assessment of extracardiac findings.

Methods: The study cohort comprised 40 consecutive patients who underwent trans-thoracic echocardiography (TTE) and ECG-CTA. TTE and ECG-gated CTA findings regarding extracardiac vascular structures, coronary arteries and airways were compared with surgical or cardiac catheterization findings. Scans were evaluated for image quality using a subjective visual scale (from 1 to 4). Effective radiation dose was calculated for each scan.

Results: Median age was 28 ± 88 days and mean weight 3.7 ± 1.5 kg. Diagnostic quality was good or excellent (visual image score 3–4) in 39 of 40 scans (97.5%). ECG-CTA provided important additional information regarding extracardiac vascular structures and airway anatomy, complementing TTE in 75.6% of scans. Overall sensitivity of ECG-gated CTA for detecting extracardiac findings as compared with operative and cardiac catheterization findings was 97.6%. The calculated mean effective radiation dose was 1.4 ± 0.07 mSv (range 1.014–2.3 mSv).

Conclusions: ECG-CTA is an accurate modality for demonstrating extracardiac structures in complex CHD. It provides important complementary information to TTE regarding extracardiac vascular structures and coronary artery anatomy. This modality may obviate the need for invasive cardiac catheterization, thus exposing the patient to a much lower radiation dose. 

Objectives: To characterize common obstetric anesthesia practices after cesarean deliveries in Israel in order to standardize postoperative pain relief protocols.

Methods: A questionnaire was completed during an interview with every obstetric anesthesia unit in all 25 delivery wards in Israel. Data were gathered on intraoperative anesthesia and analgesia protocols as well as postoperative pain relief protocols. A sub-analysis compared units whose director completed a formal obstetric anesthesia training program with those whose directors did not.

Results: Neuraxial morphine was used routinely in 12% of hospitals. No unit providing intrathecal morphine complied with American Society of Anesthesiologists guidelines for respiratory monitoring after use of neuraxial opioids. Additionally, non-steroidal anti-inflammatory drugs (NSAIDs) were used routinely in only half the wards, while patient-controlled analgesia was used infrequently. Postoperative verbal analog scores were not recorded routinely in 71% of units on postoperative day 1. The unit director's training significantly influenced the unit protocols.

Conclusions: Intrathecal morphine, the gold standard of care in cesarean deliveries, is rarely used, mainly due to shortage of staff and lack of formal obstetric anesthesia training. In addition, NSAIDs are also underused. There is a need for more formal training for obstetric anesthesiologists in Israel.

Objectives: To investigate the prevalence of hypertension and its relation to body mass index (BMI) in obese children aged 9–17 years in Israel.

Methods: Weight, height, BMI, and systolic and diastolic blood pressure (BP) (twice) were measured in children attending general and pediatric endocrine clinics. Obesity was defined as BMI ≥ 95th percentile and overweight as BMI ≥ 85th percentile. Pre-hypertension and hypertension were defined as systolic and/or diastolic BP ≥ 90th percentile for age, gender and height and BP ≥ 95th percentile respectively. In children with pre-hypertension or hypertension, repeated measurements were performed.

Results: We evaluated 264 children of whom 152 had BMI ≥ 85th percentile (study group). Their mean age was 12.5 years. The prevalence of elevated BP (both pre-hypertension and hypertension) in the study group was 44.1% and 31% at the first and second measurements respectively, compared to 11.6% and 1.9% in the normal-weight group. Hypertension was documented in 17.2% of the study group at the second measurement.

Conclusions: Elevated BP was diagnosed in 31% of overweight and obese children and adolescents. Increased awareness and early diagnosis and treatment are essential.

Objectives: To report the first results from the Serbian National Cohort study, which was started in January 2000.

Methods: Our study included 374 patients: 260 primary APS patients and 114 SLE patients with secondary APS. Antiphospholipid antibody (aPL) analysis included detection of anticardiolipin antibodies (aCL) (immunoglobulin G and M), ß₂-glycoprotein 1, and lupus anticoagulant. Echocardiography was performed in all patients, and data on myocardial infarction, unstable angina, chronic cardiomyopathy and acute heart failure were collected.

Results: There were 30.7% secondary APS patients and 9.2% primary APS patients with pseudo-infective endocarditis (P = 0.0001). Cardiac manifestations were observed in 28.7% of patients who had more than one type of antibody (category I), in 24.1% with category IIa, in 23.1% with category IIb, and in 27.8% with category IIc (P = 0.78). Age was confirmed as a significant factor for cardiac manifestations in APS patients (52.3 and 43.3 years, respectively, P = 0.001). aCL IgG and IgM positivity was related to valvular changes in all APS patients and high levels of those antibodies increased the risk of these manifestations.

Conclusions: Patients with secondary APS had a higher prevalence of valvular lesions, and some aPL types and high levels of aPL were risk factors for specific cardiac manifestations in APS patients.