Sigal Korem, PhD, Zaki Kraiem, PhD, Eitan Shiloni, MD, Oved Yehezkel, BSc, Orit Sadeh, MSc and Murray B. Resnick, MD, PhD
Background: Matrix metalloproteinases are proteolytic enzymes that degrade extracellular matrix components. Numerous studies have demonstrated that individual MMPs play a crucial role in tumor invasion and metastasis.
Objective: To examine the expression of MMPs and their inhibitor TIMP-2 in neoplastic and normal thyroid tissues.
Methods: We examined 33 cases of thyroid tumor (papillary, follicular and medullary carcinoma, follicular adenoma and multinodular goiter). MMP protein content and activity were measured by enzyme-linked immunosorbent assay and gel zymography. Immunohistochemistry was also performed.
Results: The thyroid tissues examined secreted MMP-2 and 9 as well as TIMP-2, but only MMP-2 was significantly higher in papillary carcinoma cases compared to the adjacent normal tissue or to the other tumor entities. Increased MMP-2 immunohistochemical staining was demonstrated in the neoplastic papillary epithelial component. No significant difference was seen between papillary carcinomas with lymph node metastases and those without.
Conclusions: Increased MMP-2 expression may be useful as a diagnostic marker to differentiate papillary carcinoma from other thyroid neoplasms, but it cannot serve as a useful prognostic marker.
Daniele Bendayan, MD, Gershon Fink, MD, Dan Aravot, MD, Mordechai Ygla, MD, Issahar Bendov, MD, Leonard Bliden, MD, Nir Amiran, MD and Mordechai Kramer, MD
Background: Primary idiopathic pulmonary hypertension is a rapidly progressive disease with a median survival of less than 3 years. Recently its prognosis was shown to dramatically improve with the use of epoprostenol, an arachidonic acid metabolite produced by the vascular endothelium, which increases the cardiac output and decreases the pulmonary vascular resistance and pulmonary arterial pressure. This drug enhances the quality of life, increases survival and delays or eliminates the need for transplantation.
Objective: To review the experience of Israel hospitals with the use of epoprostenol.
Methods: The study group comprised 13 patients, 5 men and 8 women, with an age range of 3–53 years. All patients suffered from arterial pulmonary hypertension. Epoprostenol was administered through a central line in an increased dose during the first 3 months, after which the dose was adjusted according to the clinical syndrome and the hemodynamic parameters.
Results: After 3 months the mean dose was 10 ng/kg/min and the pulmonary artery pressure decreased from 7 to 38%. After one year, the PAP decreased at a slower rate. Two cases required transplantation, three patients died, and seven continued taking the drug (one of whom discontinued). Four episodes of septicemia were observed. Today 10 patients are alive and well and 7 continue to take epoprostenol.
Conclusion: We found that epoprostenol improves survival, quality of life and hemodynamic parameters, with minimum side effects.
Anat Kesler, MD, Ronit Galili-Mosberg, MD and Natan Gadoth, MD
Tomas Kozak, MD and Ivan Rychlik, MD
Intractable forms of autoimmune diseases follow a rapid course, with a significantly shortened life expectancy sometimes comparable to that of malignant diseases. Immunoablative therapy, including high dose cytotoxic agents and hematopoietic autologous stem cell rescue, was recently introduced as an aggressive approach to treat autoimmune diseases that have a rapid course and are resistant to conventional therapy. The most frequent indication for this type of treatment is multiple sclerosis, seconded by systemic sclerosis. The results of immunoablative treatment with documented responses in both diseases are encouraging. The data are mature enough to begin comparative randomized studies of immunoablative versus conventional treatment to validate the benefit of the aggressive approach. A randomized trial involving SSc was recently launched (ASTIS) and a trial involving MS is under preparation. Considerably less experience with immunoablative treatment has been gained in systemic lupus erythematosus, rheumatoid arthritis, and other disorders with an autoimmune pathophysiology. Autologous hematopoietic stem cell transplantation in humans offers more long-lasting immunosuppression than reeducation of lymphocytes. In fact, allogeneic transplantation may replace the whole immune system. However, this attractive approach is still associated with considerable morbidity and mortality and is not yet justified for treatment of automimmune diseases. Non-myeloablative allogeneic transplantation and sub-myeloblative high dose cyclophosphamide without stem cell support are alternative approaches that could be explored in pilot studies.
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Jacob Lavee, MD and Yoav Paz, MD
Lotan Shilo, MD, Susy Kovatz, MD, Ruth Hadari, MD, Eli Weiss, PhD and Louis Shenkman, MD