Eyal Bercovich MD, Lital Keinan-Boker MD PhD and Shaul M. Shasha MD
Background: Previous studies suggest that exposure to starvation and stress between conception and early infancy may have deleterious effects on health later in life; this phenomenon is termed fetal origin of adult disease.
Objectives: To determine whether exposure to the Holocaust from preconception to early infancy is a cause of chronic morbidity in adulthood.
Methods: This pilot study involved 70 European Jews born in countries under Nazi rule (exposed group) during the period 1940–1945 who were interviewed to determine the presence of chronic diseases. A control group of 230 Israeli-born individuals of the same descent, age, and gender distribution were extracted from the Israel National Health Interview Survey-2 (unexposed group). The prevalence of selected risk factors and chronic diseases was compared between the groups.
Results: The prevalence of cardiovascular risk factors and morbidity was significantly higher in the exposed group: body mass index (BMI) (29.06 ± 3.2 vs. 26.97 ± 4.42, P = 0.015), hypertension (62.9% vs. 43%, P = 0.003), dyslipidemia (72.9% vs. 46.1%, P < 0.001), diabetes (32.9% vs. 17.4%, P = 0.006), angina pectoris (18.6% vs. 4.8%, P = 0.001) and congestive heart failure (8.6% vs. 1.7%, P = 0.013). The prevalence of cancer (30.0% vs. 8.7% P < 0.001), peptic ulcer disease (21.4% vs. 7%, P = 0.001), headaches/migraines (24.3% vs. 12.6%, P < 0.001) and anxiety/depression (50.0% vs. 8.3%, P < 0.001) was also higher in the exposed group.
Conclusions: These results suggest that exposure to Holocaust conditions in early life may be associated with a higher prevalence of obesity, dyslipidemia, diabetes, hypertension, cardiovascular morbidity, malignancy and peptic diseases in adulthood. These findings set the stage for further research, which might define those exposed as a high risk group for chronic morbidity.
Tania Sezin MSc, Emily Avitan-Hersh MD, Margarita Indelman MSc, Roni Moscona MD, Edmond Sabo MD, Rina Katz MSc, Shimon Pollack MD and Reuven Bergman MD
Background: Human amnion membrane (HAM) was suggested to be a superior antigenic substrate for immunoblotting in detecting autoantibodies of autoimmune bullous skin diseases.
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.
Arie Apel MD, Meirav Kedmi MD, Etai Levi MD, Miriam Berkowicz MD, Yaron Davidovitz MD, Abraham Kneller MD, Elena Ribakovsky MD, Avichai Shimoni MD, Arnon Nagler MD MSc and Abraham Avigdor MD
Background: Acute lymphocytic leukemia (ALL) is a rare disease with a poor outcome in adults. Over the years different protocols have been developed with the aim of improving the outcome. The German study group protocols (GMALL), which are the most frequently used in our institutions, changed significantly between the periods 1989–93 and 1999–2003.
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.
Sarah Kraus PhD, Inna Naumov PhD, Shiran Shapira PhD, Dina Kazanov MSc, Ilan Aroch MSc, Arnon Afek MD PhD, Oded Eisenberg PhD , Jacob George MD, Nadir Arber MD MSc MHA and Ariel Finkelstein MD
Background: Atherosclerosis is a complex vascular inflammatory disease. In the last decade it was suggested that non-steroidal anti-inflammatory drugs (NSAID) and in particular inhibition of cyclooxygenase (COX)-2 are associated with an increase in cardiovascular morbidity and mortality. Aspirin is known to reduce the incidence and mortality from ischemic heart disease and is a mainstay in the prevention of vascular complications of atherosclerosis.
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.
George Habib MD MPH, Munir Nashashibi MD and Sara Gips MD
Background: Computed tomography pulmonary angiography (CTPA) is considered the method of choice for diagnosing pulmonary embolism (PE). In most patients with impaired renal function, ventilation-perfusion (V/Q) scanning is the preferred modality.
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.
Sharon Baum MD, Yaron Zafrir MD and Aviv Barzilai MD MSc
Shira Bezalel MD, Keren Mahlab Guri MD, Daniel Elbirt MD, Ilan Asher MD and Zev Moshe Sthoeger MD
Type I interferons (IFN) are primarily regarded as an inhibitor of viral replication. However, type I IFN, mainly IFNα, has a major role in activation of both the innate and adaptive immune systems. Systemic lupus erythematosus (SLE) is a chronic, multi-systemic, inflammatory autoimmune disease with undefined etiology. SLE is characterized by dysregulation of both the innate and the adaptive immune systems. An increased expression of type I IFN-regulated genes, termed IFN signature, has been reported in patients with SLE. We review here the role of IFNα in the pathogenesis and course of SLE and the possible role of IFNα inhibition as a novel treatment for lupus patients.
Oded Shamriz MD, Inbal Cohen-Glickman PharmD, Shimon Reif MD and Eyal Shteyer MD
With growing awareness of the importance of pain control in all procedures, the use of lidocaine-prilocaine cream (EMLA) for all ages is increasing. Lidocaine-prilocaine cream has been implicated as a cause of methemoglobinemia. Diagnostic clues may be oxygen-resistant cyanosis and an oxygen ‘‘saturation gap’’ between arterial blood saturation and pulse oximetry. Treatment with intravenous methylene blue is often effective. Since EMLA is often mistakenly considered risk-free it is routinely applied by medical staff in the emergency room. Subsequent to the case of EMLA-induced methemoglobinemia in an 8 year old girl we wish to alert the medical community to this phenomenon, and in this work review the relevant literature.