תוצאת חיפוש

Intravenous Immunoglobulins Treatment of Patients with Graves' Ophthalmopathy

Adi Leibe, Yair Levy, Yehuda Shoenfeld

Department of Medicine B and Research Unit of Autoimmune Diseases, Chaim Sheba Medical Center, Affiliated to Sackler Faculty of Medicine, Tel-Aviv University

Graves' ophthalmopathy is an autoimmune disease manifested as exophthalmus, lid lag and diplopia. As in the accompanying autoimmune thyroid disease, there is an autoimmune homoral and cellular attack on the orbita, mainly the retro-orbital tissues.

Steroids are the comerstone of therapy. We reviewed the evidence for a similar therapeutic effect of I.V., immunoglobulins (IVIGs) and their better side affect profile as compared to steroids. We also described an impressive therapeutic success with IVIG given to a patient with resistant ophthalmopathy. The clinical picture of Graves' ophthalmopathy is attributed to a pathologic hyper - activation of orbital fibroblasts, deposition of collagen and glycosaminoglycans in the extra-cellular matrix and eventually fibrosis. These are mediated by leucoregulin, IL-1, IFN-gamma, and TGF-beta - all secreted by lymphocytes and mast cells in the retorbital space.

Another mode of cell activation is by binding of autoantibodies (presumably thyroid stimulating Ab's) to an antigenic determinant on the surface of fibroblasts.

I.V. immunoglobulins, known today to be active in a variety of autoimmune processes, exert their effect on autoantibodies, complement, phagocytic cells etc. IVIGs also inhibit orbital lymphocytes and fibroblasts through inhibition of IL-1 or/and TGF-beta.

יעקב ברקון ומאיר שליט

היח' לאלרגיה ואימונולוגיה קלינית, האגף לרפואה פנימית, ביה"ח הדסה, ירושלים

בשנים האחרונות, הצטבר מידע רב על מעורבות ליקוטריאנים בגנחת הסימפונות ובמחלות דלקתיות למיניהן. במטרה למנוע את פעולתם בתהליך האלרגי-דלקתי, פותחו תרופות נוגדות ליקוטריאנים (נלק"ט), ולאחר שהוכחה יעילותן, הן הוכנסו לשימוש נרחב בטיפול בחולי גנחת. לאחרונה התברר, שתרופות אלו פעילות גם בנזלת אלרגית וכעת נערכים מחקרים רב-מרכזיים במטרה לבדוק את יעילותן כנגד מחלה זו. כן דווח בשנתיים האחרונות על הצלחות טיפוליות של נלק"ט בחולים הלוקים בחרלת כרונית (ח"כ). המטרה בסקירה זו היא לעמוד על תפקיד הליקוטריאנים בחרלת כרונית ולסכם את הידוע לגבי יעילות תרופות נלק"ט בטיפול בלוקים במחלה זו.

מחמוד אבו-שקרה

היח' למחלות אוטואימוניות שיגרוניות, מרכז רפואי סורוקה ואוניברסיטת בן-גוריון, באר-שבע

בשנים האחרונות, בעבודות מרובות הודגם קשר בין ממאירות ותופעות אוטואימוניות ושיגרוניות. קשר זה הוא דו-כיווני. מחד גיסא, קיימת שכיחות יותר גבוהה של סך הממאירות בחולים עם דרמאטומיוזיטיס, פולימיוזיטיס וסקלרודרמה בהשוואה לכלל האוכלוסייה. כמו כן, בחולים עם דלקת מיפרקים שיגרונתית וחולי זאבת אדמנתית מערכתית, קיים סיכון מוגבר ללקות בממאירות המאטולוגית או לימפו-פרוליפרטיבית.

מאידך גיסא, מיגוון רחב של תופעות אימונולוגיות וביטויים שיגרוניים שונים יכולים להתרחש בחולים עם מחלקה ממארת. תופעות אלו יכולות להוות תוצאה של ייצור נוגדנים עצמיים, חדירה של ריקמה שאתית למיפרקים, תיסמונות פארא-ניאופלסטיות שונות, או ביטויים שיגרוניים מישניים לכימותרפיה.

בגיליון זה של "הרפואה" מדווחים חביב וחב' על חולה עם סרטן הריאה אשר הביטוי הראשוני למחלתו היה כאב בברכיים ותיסמונת אוסטואתרופתיה היפרטרופית.

בבמה זו, אסקור את המנגנונים והתופעות האוטואימוניות השונות בקרב חולים עם מחלה ממארת ואתייחס לתיסמונת אוסאוארתרופתיה היפרטרופית.

שי שרוט¹, יואב צפמן¹, יהודה שינפלד²

¹המח' למחלות עצבים, המרכז הרפואית תל-אביב, ²מח' לרפואה פנימית ב' והמרכז למחלות אוטואימוניות, בי"ח שיבא, תל-השומר

תיסמונת האנטיפוספוליפידיים, antiphospholipid syndrome (APS) היא מחלה רב-מערכתית שבה מעורבים נוגדנים ואנטיגנים שונים. הפרעה האוטואימונית מתבטאת קלינית באירועים פקקתיים-תסחיפיים נשנים (עורקיים וורידיים), בהפלות עצמוניות נשנות, בתרומבוציטופניה ובכייל גבוה של נוגדנים כנגד פוספוליפידים ((antiphospholipid-antibodies - aPL וכן של נוגד קרישה זאבתי (lupus anticoagulant - LA). התיסמונת יכולה להתרחש משנית למחלות אוטואימוניות אחרות (כמו זאבת אדמנתית מערכתית systemic-lupus-erythematosus (SLE), לממאירויות או לזיהומים וכן כתגובה לתרופות. כשלא נמצאת סיבה ראשונית מעין אלו להתהוות התיסמונת, היא מוגדרת כראשונית (primary APS).

הנוגדנים הנמנים עם משפחת ה- aPL מאותרים בבדיקה שבה נמדדת תגובתיות (reactivity) חיסונית כלפי קרדיוליפין (aCL) ופוספוליפידים למיניהם הטעונים שלילית, בנוכחות או ללא נוכחות  ביתא 2 – גליקופרוטאין או קופקטורים חלבוניים אחרים, או ע"י תגובתיות חיסונית כלפי ביתא 2 – גליקופרוטאין (הידוע כקופקטור חיוני לקישור ה- aPL) או קופקטורים חלבוניים אחרים לבד, או על ידי יכולתם לעכב את מנגנון הקרישה בתבחיני קרישה התלויים בפוספוליפידים (LA=).

לא כל בני-האדם עם aPL יהיו תסמיניים. בסקר פרוספקטיבי של בנק הדם התגלה, שב- 6.5% מהאוכלוסייה הכללית אובחנו בתבחין ELISA נוגדנים מסוג IgP-aPL. לעתים קרובות, יורד כיל-ה- aPLלטווח התקין עם הזמן, ללא אירועים פקקתיים.

בחולים הלוקים ב- APS, דווח על ביטויים קליניים שונים, הכוללים סיבוכים המאטולוגיים, סיבוכים בעור, מחלת מסתמי הלב והיפגעות הכליות. בנוסף, דווח על ביטויים נירולוגיים שונים המערבים בעיקר את מערכת העצבים המרכזית. בסקירה זו, נדונים ההיבטים הנירולוגיים של תיסמונת הנוגדנים האנטיפוספוליפידיים.
 

Pulmonary Adenocarcinoma in Myasthenia Gravis - Auto-Immunity and Late Development of Malignancy

Yitzhak Rosen, Yair Levy, Yehuda Shoenfeld

Dept. of Internal Medicine B, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

We report a 75-year-old man with myasthenia gravis for many years, who was hospitalized because of cough, fever, and dyspnea. Chest x-ray revealed a bilateral pleural effusion. Adenocarcinomatous cells were found in the pleural fluid. Computerized tomography of the chest showed widespread pulmonary dissemination of the tumor.

The relationship between myasthenia gravis, an autoimmune disease involving the motor end-plate, and malignancy (thymoma) has been widely recognized. Current literature documents few reports of lung malignancies with concurrent development of myasthenia gravis. A tentative explanation, based on current research, is provided for the possible role of myasthenia gravis and the late development of lung cancer. Moreover, a model for the autoimmune phenomenon and the development of late malignancies will be provided with explicit explanations. It is important to search for occult, developing malignancies in newly diagnosed autoimmune diseases.

Cells-Preliminary Report Immunohistochemical Identification of Testicular Germ

Batia Bar-Shira Maymon, Gedalia Paz, Leah Yogev, Ron Hauser, Letizia Schreiber, Amnon Botchan, Haim Yavetz

Institute for Fertility Study, Lis Maternity Hospital; Pathology Institute, Tel Aviv-Sourasky Medical Center; and Sackler Faculty of Medicine, Tel Aviv University

The use of testicular spermatozoa for intracytoplasmic sperm injection introduced a new treatment modality for management of male infertility.

Since testicular biopsies of non-obstructive azoospermic men are not homogenous in their histological patterns, identification with certainty of focal spermatogenesis might be difficult, particularly in those with small foci of spermatogenesis. We used an immunohistochemical marker of the male germ line, an antibody generated against RBM (RNA-binding-motif), to recognize with high precision the presence of germ cells in the biopsy. Biopsies of 30 men with azoospermia, most with non-obstructive azoospermia and a few with obstruction of the vas deferens, were evaluated.

Immunohistochemical staining for RBM protein contributed to the detection and accuracy of the identification of germ cells. Furthermore, this immunohistochemical technique aided the histopathologist to focus on even small foci of spermatogenesis. Absence of the protein expression confirmed the diagnosis of Sertoli-cell-only syndrome. The results indicate that expression of RBM can be a diagnostic marker for identifying the germ cells of small concentrations of spermatogenesis. This method can enhance the accuracy of histopathological evaluation of testicular biopsies that had formerly relied mainly on hematoxylin-and-eosin staining.

אורה שובמן, בוריס גילבורד, פנינה לנגביץ', יהודה שינפלד

המח' לרפואה פנימית ב' והיחידה לחקר מחלות אוטואימוניות, המרכז הרפואי שיבא תל השומר והפקולטה לרפואה סאקלר, אוניברסיטת תל אביב

מילות מפתח:

נוגדני RA33, RA33, מחלות אוטואימוניות, אורה שובמן, בוריס גילבורד, פנינה לנגביץ', יהודה שינפלד, שובמן, גילבורד, לנגביץ', שינפלד

Sublingual Immunotherapy for Allergic Diseases

David Nelken

Medical Building, Sprinzak St., Tel Aviv

4 patients suffering from severe pollinosis and/or allergic rhinitis, with or without asthma, were treated as follows: 30 minutes before breakfast the vaccine was dropped sublingually and retained for 2-3 minutes before being swallowed. It was a commercial preparation of allergen, diluted 50% w/v in glycerin.

This stock solution was then diluted in physiological saline containing 0.05% human albumin and kept refrigerated in a dark glass bottle for up to 4 weeks. Of the first dilution which contained 10 Au/ml, 1 drop was given on day 1 and 1 drop more each day until days 5 to 17, when 5 drops were given daily. Then 1000 and then 2500 Au/ml were given sequentially in the same manner, and finally 5000 was given for up to 2 years. A maintenance dose of 3 drops of 5000 Au/ml twice weekly was then prescribed.

41 patients showed striking clinical improvement after about 6 months of treatment. A definite reduction in the use of other medications was achieved in all. Sublingual immunotherapy is practically free of unwanted side effects and easy to self-administer at home.

To establish the specificity of sublingual immunotherapy, patients who had severe allergic symptoms to one pollen allergen causing symptoms in the spring and to a second in the autumn, were first immunized sublingually against a single allergen. A year later, after symptoms due to this allergen had subsided, and if symptoms caused by the second allergen had not improved, immunization against the second allergen was started.

Sublingual immunotherapy acts by increasing mucosal antibodies at the site of entry of the allergen into the respiratory tract. It is a safe and practical procedure with results comparable to subcutaneous allergy injections.

Effect of Specific Inspiratory Muscle Training on Dyspnea and Exercise Tolerance in Congestive Heart Failure

Paltiel Weiner, Joseph Waizman, Rasmi Magadle, Noa Berar-Yanay, Benny Pelled

Depts. of Medicine A and Cardiology, Hillel Yaffe Medical Center, Hadera

It has been shown that the inspiratory muscles of patients with congestive heart failure (CHF) are weaker than normal. This weakness may contribute to dyspnea and limit exercise capacity. But respiratory muscles can be trained for increase in both strength and endurance. This study was designed to evaluate the effect of specific inspiratory muscle training (SIMT) on muscular performance, lung function, dyspnea and exercise capacity in moderate heart failure.

10 patients with CHF (NYHA functional class II-III) received 1/2 hour of SIMT daily, 6 times/week, for 3 months. They started breathing at a resistance 15% of their Pimax for 1 week and the resistance was then increased incrementally to 60%. Spirometry, inspiratory muscle strength and endurance, and the 12-minute walk test were performed before and after the training period. All showed an increase in inspiratory muscle strength and endurance. This was associated with a small but significant increase in FVC, a significant increase in the distance walked (458±29 to 562±32 m, p<0.01), and improvement in the dyspnea index score.

SIMT resulted in increased inspiratory muscle strength and endurance. This increase was associated with decreased dyspnea and an increase in submaximal exercise capacity. SIMT may prove to be useful complementary therapy in CHF.

Clinical and Immunological Characteristics of HIV-Positive AIDS in Children in Northern Israel

E. Kedem, A. Etzioni, E. Shahar, S. Pollack

Institute of Immunology, Allergy and AIDS and Dept. of Pediatrics A, Rambam Medical Center and B. Rappaport Faculty of Medicine, The Technion, Haifa

We are treating 11 children in our AIDS clinic. All were infected by vertical transmission from carrier mothers. However, among 31 HIV-carrier AIDS patients who were under follow-up during pregnancy, supposedly taking zidovudine prophylaxis, only 1 (3.3%) gave birth to a baby infected with HIV. Our children with HIV and AIDS are 3 months to 12 years of age (average 4.5 years); mean age at diagnosis was 18 months. All are either symptomatic or have laboratory evidence of progressive immunodeficiency, 1 is asymptomatic (N2), 1 has mild symptoms (A2) and the rest present significant symptoms or AIDS-defining disease. All have moderate to severe immunodeficiency, as evidenced by CD4+ cells counts. 60% have rapidly progressive disease, based on their symptomatology and immune state, whereas clinical reports in the literature point to only 10-15%. However, the average CD4+ cell count was 22% (749/mm³) at diagnosis and 22% (759/mm³) at last follow-up. These stable findings during an average follow-up of 28 months probably reflect the effect of medical and supportive treatment.

All received antiretroviral medication consisting of a combination of 2 or 3 drugs. 8 of 11 also received prophylactic treatment against opportunistic infections and 8 of 11 are clinically well. Routine follow-up and a good relationship with the patient's family increase cooperation and promote optimal medical treatment, and consequently improve the clinical condition and quality of life.

Legionellosis in Israel

Ida Boldur, Silviu Hoffmann, Regina Kazak, Batzion Benjamin

Institute of Microbiology, Assaf HaRofeh Medical Center, Zrifin and Dept. of Life Sciences, Bar-Ilan University, Ramat Gan

Infection with Legionella remains an important cause of disease and death. We analyzed our laboratory data from 1993 through 1997, augmented by our 20 years of experience. The incidence of Legionella as a cause of pneumonia varied in our study from 5%-9%, with a slight increase during the winter. Isolation of these microorganisms from different water sources was higher during the summer and ranged from 7%-70%.

Special laboratory tests are necessary to diagnose the disease and monitor these bacteria in water samples. The serologic method - indirect immunofluorescent assay -- for 41 serogroups of Legionella was the main diagnostic method used. Legionella sg. 1 was the most frequent cause of the disease, with an incidence of 52% in 1993, decreasing to 15% in 1997. An increase in the incidence of seropositivity to "other Legionellae" is characteristic for our country.

No correlation was found between the incidence of isolation of a specific strain and exposure. However, it is well known that the disease is overtreated but underdiagnosed, which requires reversal. Larger studies of Legionella colonization in water supplies and in air are needed in order to establish the risk of infection. Water sources are presently under-studied, as are respiratory devices in hospitals, or they are not studied at all in Israel, such as in mist machines in supermarkets, in dental clinics, and in ships and airplanes.

Kaleidoscopic Autoimmunity

Yehuda Shoenfeld

Unit for Study of Autoimmune Diseases and Medical Dept. B, Sheba Medical Center, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University

We describe an 18-year-old girl with idiopathic thrombocytopenic purpura (ITP) who developed chronic active hepatitis following splenectomy that cured the ITP. This is a phenomenon in which an organ belonging to the immune system is resected, which results in cure of one autoimmune disease but in the emergence of another, apparently unrelated, second autoimmune disease. We refer to this phenomenon as kaleidoscopic autoimmunity, explaining that some autoimmune diseases are not induced by autoantigen-driven mechanisms, but rather result from immune dysregulation.

Islet Autoantibody Assays in Type I Diabetes can Replace ICA Test

Daniel Lazar, Naomi Weintrob, Natalia Abramov, Sara Assa, Konstantin Bloch, Regina Ofan, Hadassa Ben-Zaken, Pnina Vardi

Institute for Pediatric Endocrinology and Diabetes, Schneider Children's Medical Center, Petah Tikva and Felsenstein Medical Research Center, Tel Aviv University

Islet cell antibodies (ICA) continue to serve as the basis of the principal serological test for definition of active autoimmunity of beta-cells. Its disadvantages are the need for human pancreatic tissue and difficulty in obtaining quantitative results. In the past decade biochemically-defined beta-cell antigens were described, leading to the development of sensitive and specific autoantibody assays, to predict insulin-dependent diabetes mellitus (IDDM). We examined the value of combined biochemically-based serological assays, such as autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and ICA512 (ICA512A) to replace the traditional ICA assay.

Blood samples of 114 newly diagnosed IDDM patients, aged 12‏5 yrs (range 2 months - 29 years) were tested for ICA (indirect immunofluorescence), IAA, GADA and ICA512A (radiobinding assay). The latter 2 assays were performed using recombinant human [35S]-labeled antigen produced by in vitro transcription/translation. We found that fewer sera scored positive for ICA and/or IAA (80.7%, 92/114) than for 1 or more of IAA, GAD, or ICA512 (88.6%, 101/114). We conclude that combined testing for IAA, GAD and ICA512 can replace the traditional ICA/IAA test to predict IDDM and is helpful in the differential diagnosis of insulin-dependent and noninsulin-dependent diabetes.

Fatal Asthma in Children: Preventable?

Haim Bibi, Jamal Mahamid, David Shoseyov, Michael Armoni, Zvika Liss, Menachem Schlesinger

Pediatrics Dept., Barzilai Medical Center, Ashkelon (Affiliated with the Faculty of Health Sciences, Ben-Gurion University of the Negev); Pediatric Intensive Care Unit, Bikur Holim Hospital, Jerusalem, and Kupat Holim Klalit, Darom District

Sudden death from asthma is rare but occurs in the young age group. We recently faced this rare situation, when 3 asthmatic children were dead on arrival at the local emergency room. All 3 had been treated with beta-2 agonist inhalation on a regular basis, without anti-inflammatory treatment. 2 of the children died while inhaling the beta-2 agonist. It is important that there be clear guidelines and full education about the management of asthma, during and between exacerbations, to prevent such deaths.

Mixed Uterine Mesodermal Tumors: Clinical and Pathological Characteristics

Samuel Ariad, Alexander Rabinovitz, Ilana Yanai-Inbar, Benjamin Piura

Depts. of Oncology and of Pathology, and Gynecology-Oncology Unit, Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

During 1971-1996, 17 patients with mixed mesodermal uterine tumors were treated. Average age at diagnosis was 67.3 years, 12/17 were of European and 5/17 of Afro-Asian extraction. The overall 5-year survival was 21%. 10/17 patients had mixed mesodermal tumors with a heterologous mesenchy-mal element, and 7/17 had a homologous mesenchymal element (carcinosarcoma). 6/17 had another primary malignancy, including breast cancer (3/17), bilateral metachronous breast tumor (2/17), and malignant lymphoma of the neck region (2/17). All 3 with breast cancer had previously been treated with tamoxifen. 1 had simultaneous mesodermal tumor and ovarian thecoma. Simultaneous autoimmune manifestations occurred in 2/17, including thrombocytopenic purpura in 1, and myasthenia gravis in another. Mesodermal tumor of the uterus is a relatively rare malignancy with aggressive behavior and poor prognosis. It also had unusual associations with other primary tumors, hormonal treatment, and autoimmune manifestations.