Tessa Chelouche MD
Born in Czechoslovakia, psychiatrist Leo Eitinger (1912-1996) became internationally recognized for research on his fellow concentration camp inmates. He graduated as an MD in 1937, but being Jewish was prohibited from practicing as a doctor. When the Nazis moved into the area he was forced to flee to Norway, where in 1940 he was again deprived of his right to practice medicine. In 1942 he was arrested and deported to Auschwitz. There, as a physician inmate, he was able to help and in many cases save his fellow prisoners, not only with his medical skills but by falsifying prisoners' documents and hiding them from their Nazi captors. One of his patients was Elie Wiesel. Eitinger survived the camps but was forced to join a "death march." After the war he resumed medical practice in Norway, specializing in psychiatry. With his personal experience and knowledge of the suffering of camp survivors, he dedicated his life to studying the psychological effects of traumatic stress in different groups. Eitinger's academic contributions were crucial in the development of this area of research on the effects of excessive stress, laying the foundations for the definition of post-traumatic stress disorder and the post-concentration camp syndrome, thus facilitating recognition of the medical and psychological post-war conditions of the survivors and their resultant disability pensions.
George M. Weisz MD FRACS MA and William R. Albury BA PhD
Reinhard Heydrich, architect of the “Final solution of the Jewish problem,” had a meteoric career in the SS. He organized the Wannsee Conference and created the SS killing squads. Under his leadership as Reich Protector of Bohemia and Moravia, the suppression of the Czech community was brutal. An attempt on his life in Prague was unsuccessful but it left him severely injured and he died eight days later. Reviewing the available information on his hospital treatment and the autopsy report, it is suggested that Heydrich received substandard medical treatment, quite likely a result of political interference from rival members of the SS hierarchy.
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.
Eyal Kramer MD, Oscar Herman MD, Jacob Frand MD, Lior Leibou MD, Letizia Schreiber MD and Hananya Vaknine MD
Background: Basal cell carcinoma (BCC) is the most common malignancy in humans. Several factors have been associated with the biological behavior of these tumors, including histopathologic type, depth of tumor invasion, perineural invasion, and the expression of several biologic markers including Ki67, a proliferative marker. Previous studies assessing the relationship between the proliferative fraction, as expressed by Ki67, and the histologic variants of BCC as well as its association with the tendency to recur, failed to illustrate significant statistical correlation.
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.
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.
Amit Sastry MD, Justin Steele MD and Avram Cooperman MD