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.
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.
Amit Sastry MD, Justin Steele MD and Avram Cooperman MD
Marina Pekar, Gilad Twig MD, Alex Levin MD and Howard Amital MD MHA
Ori Galante MD, Ella Abramovich MD, Anat Nevo-Shor MD and Yaniv Almog MD
Maitseo Kuno Nwako-Mohamadi MBChB BAO MSc, Vidushi Madan MD, Matthew N. Tanko MBBS FMCPath (Nig) and Sandro Vento MD