ינינה גלבויז (1), שרה שפירו (2), ניצה להט (2), אריאל מילר (1,3)

(1) היחידה לנירואימונולוגיה, המח' לנירולוגיה, (2) היחידה לחקר אימונולוגיה, המרכז הרפואי כרמל, הטכניון – הפקולטה לרפואה, (3) מכון רפפורט למחקר במדעי הרפואה, חיפה

אנזימי המטריקס-מטלופרוטאינאזות (matrix metal-loproteinases - MMP's) (אממ"פ)* הם משפחת אנזימים פרוטאוליטיים אשר, יחד עם מעכביהם הריקמתיים – TIMs, מעורבים בעיצוב המירקם החוץ-תאי (ECM) (מח"ת – מירקם חוץ-תאי) במיגוון מצבים פיזיולוגיים, כגון התפתחות עוברית וריפוי פצע. לאחרונה, מצטברות עדויות למעורבות אממ"פ גם במיגוון רחב של מחלות, כגון התפשטות גרורות, טרשת העורקים, מצבי דלקת ומחלות אוטואימוניות.

בתהליכים דלקתיים של מערכת העצבים המרכזית, האממ"פ הם הגורם העיקרי בהרס מחסום הדם-מוח, בהתהוות בצקת מוחית, בהסננת תאי דלקת, בתהליכי הרס מיאלין ובהתהוות צלקת הגליה במוח. פעילות מוגברת של MMPs אובחנה בבעלי-חיים חולים בדגם ניסיוני של מחלות דה-מיאליניות וטרשת נפוצה. רמות גבוהות של אממ"פ, בעיקר MMP-2 ו-MMP-9, התגלו שינויים בפרופיל האממ"פ דווחו גם בהקשר של דלקות עוצבה חיידקיות ונגיפיות. כמו כן, למרות סתירות מסוימות במימצאים, נראה כי אממ"פ מעורבים גם בתהליכי הצטברות חלבון הביתא-amyloid במחלת אלצהיימר. מעורבות אממ"פ במחלות מערכת העצבים המרכזית מעוררת עניין מיוחד בזכות יכולתם לשמש בסימנים לפעילות המחלה ובזכות הפוטנציאל הטיפולי הטמון בשימוש במעכבי אממ"פ.

עמירם כ"ץ, יאיר שפירא

המח' לשיקום ד', ביה"ח "לוינשטיין", רעננה, ביה"ח "אסותא", תל-אביב

לאדם, כמו ליונקים אחרים, מנגנון ויסות-טמפרטורה שנועד לשמר את טמפרטורת הגוף בטווח המאפשר פעילות פיזיולוגית תקינה. בגיל הזיקנה, משתבש מנגנון זה ואיננו יעיל כמו בגיל צעיר. לשיבוש זה סיבות אפשריות אחדות, וקיימים חילוקי דעות בין החוקרים על המשמעות של חלק מהן.

Rational Use of Albumin 

Emanuel Sikuler, Aviel Shapira, Shlomo Mor-Yosef, Pnina Shlaeffer, Dafna Slovik, Madlen Brutin, Gabriel Gurman

Divisions of Medicine and Surgery, Hospital Administration, Quality Control Unit, Pharmacological Service, Nursing Service, and Division of Anesthesiology; Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

The use of albumin has been a matter of debate since its introduction in the 1940's. Albumin is not only expensive but may also be harmful when administered inappropriately. Until recently our use of albumin was controlled by a number of authorized physicians who signed all albumin prescriptions.

In August 1998, a multidisciplinary team reviewed the indications for albumin use and introduced simple guidelines for its supply and administration. As a result, the use of albumin has decreased by almost 70%. This indicates that rational use of albumin can be achieved by appropriate guidelines, without requiring administrative limitations. We believe that this conclusion holds true for other diagnostic and therapeutic procedures as well.

Penile Prosthesis for Erectile Dysfunction: Long-Term Follow-Up 

Ofer N. Gofrit, Ofer Z. Shenfeld, Ran Katz, Amos Shapiro, Ezekiel H. Landau, Dov Pode

Urology Dept., Hadassah University Hospital, Jerusalem

Our armamentarium for the treatment of erectile dysfunction has recently been expanded by addition of Viagra and the MUSE. However, their long-term results are still unknown. The insertion of a penile prosthesis is invasive, expensive, and irreversible, but under optimal condition provides an acceptable, definitive solution for erectile dysfunction. We evaluated our long-term results with penile prosthesis insertion (PPI).

From 1987-1998, 57 patients underwent PPI in our department. Mean age was 55 years and the common causes of erectile dysfunction were atherosclerotic disease (23), radical pelvic surgery (15), and diabetes mellitus (14). Semirigid prostheses were inserted in 12 and inflatable prostheses in 45, including 42 single-component and 3 multi-component prostheses.

Recently we interviewed these patients by telephone, using a standard questionnaire. Those not satisfied with the surgical results (83% of the living patients) were examined in our clinic. Mean follow-up was 53 months. In 37 (84%) the prosthesis was mechanically functional (rates after 1, 5 and 10 years were 87.8%, 80%, and 75%, respectively). In only 2 (2.5%) had serious complications led to prosthesis removal.

All mechanical failures had occurred in those with inflatable prostheses after a mean of 48.5 months (range 4-113). At the time of the survey 68% were sexually active and 64% were satisfied with the surgical result. We conclude that PPI is safe treatment for erectile dysfunction. Although the rate of mechanically functioning prostheses decreases with time, modern multi-component prostheses may lead to better mechanical results.

Experience with 100 Liver Transplant Recipients 

Ezra Shaharabani, Ziv Ben-Ari, Nathan Bar-Nathan, Alex Yusim, Rivka Shapira, Ran Tur-Kaspa, Zaki Shapira, Eytan Mor

Transplantation Dept., Liver Institute, Rabin Medical Center; and Pediatric Gastroenterology Institute, Schneider Children's Medical Center, Petah Tikva

Liver transplantation is the treatment of choice for end- stage liver disease. During the past 8 years we performed 102 liver transplants in 84 adults and 16 children. In the adults, 9 were combined transplants: 1 a liver-pancreas transplant for type I diabetes, and 8 liver-kidney transplants. In the children, transplants included 5 whole-livers, 5 left-lateral liver segments from living-related donors, 4 reduced-grafts of right or left lobes, and 2 split left-lateral segments.

At a mean follow-up of 31 months (range 1-96) 70 were alive, 3 had died during surgery and 15 during the first postoperative months. Mortality was due to primary graft non-function (7), sepsis (10), intracranial hemorrhage (1), tumors (4), recurrent hepatitis B (2), biliary strictures (2) and chronic rejection (1). The 1- and 4-year survival rates were 79.5% and 69.6%, respectively.

After transplantation, 10 developed biliary stricture (5 corrected by balloon dilatation) and 8 anastomotic stricture (7 corrected by surgery), and there were 2 multiple intra-hepatic strictures. There was hepatic artery thrombosis in 5, including 4 children. In 3, grafts were salvaged by thrombectomy and 2 others underwent re-transplantation. In those who survived transplantation by more than 1-month, recurrent hepatitis B was seen in 6 of 17 (35%) and recurrent hepatitis C in 12 of 19 (63%).

Thus, results of our first 100 liver transplants are similar to those reported by larger centers, showing that in an appropriate setting good results can be achieved by small transplant programs.

Mitral Valve Repair in Ischemic Cardiomyopathy with Severeleft Ventricular Dysfunction

Dani Bitran, Ofer Merin, Jeffrey Fisher, Nadiv Shapira, Marc W. Klutstein, Shuli Silberman

Depts. of Cardiothoracic Surgery, Anesthesiology and Cardiology, Shaare Zedek Medical Center, Jerusalem

Patients with ischemic mitral insufficiency and poor left ventricular function are high operative risks. We present 101 patients who had mitral valve repair in our department: 21 had severely reduced left ventricular function, 19 were in NYHA functional Class IV, and 2 in Class III. All had concomitant coronary artery bypass.

There was no early operative mortality, but there were 2 late deaths (9.6%). At follow-up (3-36 months) all valves were functioning normally, 9 patients (43%) were in NYHA functional Class I, and 4 (19%) in Class II.

Our experience shows that repair of ischemic mitral insufficiency in the presence of severe left ventricular dysfunction can be performed with good results, and is preferable to mitral valve replacement. Late follow-up showed significant symptomatic improvement.

Man in a Hot Climate - Early Studies of the Institute of Military Physiology 

Ezra Sohar, Yair Shapiro, Yoram Epstein

Institute of Military Medicine, Medical Corps, Israel Defense Forces and Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer

In the 1950's many IDF soldiers were hospitalized for heat stroke - about 25% of whom died. Analyzing these cases revealed that commanders misinterpreted human ability to perform in the heat and ignored basic concepts of fluid and electrolyte balance and heat load.

In the early 1960's a series of studies was conducted with regard to soldiers' performance in the heat. The first study (1959), which later became a classic, was conducted during a 21-day march from Eilat to Metula, crossing all climatic zones of Israel. The study was followed by other investigations which approached the issues of voluntary dehydration, fluid consumption vs sweat loss, salt additives, and the effect of heat load on performance.

Based on these early studies, proper regulations were issued to field officers. Over the years, the lessons learned from these studies saved many lives. The number of cases of heat stroke and of other climate-related injuries was dramatically reduced, and performance was enhanced.

Prediction of Physiological Response from Mathematical Models 

Yoram Epstein, Yuval Heled, Daniel Moran, Yair Shapiro

Institute of Military Medicine, Medical Corps, Israel Defense Forces and Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer

The ability to predict the physiological responses of workers exposed to extreme environmental conditions, has been a challenge to environmental physiologists for more than 3 decades. Therefore, mathematical models have been developed to predict metabolic rate under various levels of work intensity and dynamic changes in body temperature and heart rate.

Based on the effect of exercise on the cardiovascular system, a model was developed to predict mean arterial blood pressure as a function of heart rate. Physiological strain could also be estimated on the basis of thermoregulatory and cardiovascular strains.

This paper summarizes knowledge accumulated during 25 years of studies in the field of mathematical modeling of physiological parameters. Besides analyzing the logic underlying each model, it explains the scientific approach in developing a model from its early concept to the model's application in the field.

Cortical Blindness Following Coronary Angiography 

Addie Ron, Simcha Meisel, Myra Shapiro-Feinberg,Herman O. Klein

Depts. of Medicine, Cardiology and Diagnostic Imaging,Meir Medical Center, Kfar Saba

Cortical blindness has been occasionally reported as a complication after cerebral angiography, but is rare after coronary angiography. The contrast agent is believed to be responsible for the sudden development of blindness. Although the exact mechanism is unknown, it appears that the contrast agent disrupts the blood brain barrier, mostly in the occipital areas.

We report a 77-year-old man who suddenly developed transient, bilateral cortical blindness 4 hours after coronary angiography. Using contrast enhancement, the CT scan showed typical, symmetrical involvement of both occipital lobes. There were no other neurological deficits. Vision and CT findings returned to normal within 48 hours.

Atypical Mycobacterial Cervical Lymphadenitis in Children

B. Klin, I. Boldur, J. Sandbank, Z. Schpirer, I. Vinograd

Depts. of Pediatric Surgery, Microbiology and Pathology, Assaf Harofeh Medical Center, Zerifin, and Sackler Faculty of Medicine, Tel Aviv University

Scrofula (mycobacterial cervical lymphadenitis) has been well-known for thousands of years. Atypical mycobacteria were first categorized by Timpe and Runyon in 1954. Treatment has varied over the centuries, from exclusion therapy in ancient Greece, through digitalis, iodide, chemotherapy, and surgical excision. The varied differential diagnosis and consequent diagnostic and therapeutic challenges make reassessment of this almost forgotten disease necessary.

21 patients with typical mycobacterial cervical lymphaden„itis seen in over the past 5 years were reviewed. Age distribution ranged from 1-14 years, with peak incidence at 4 years; 9 were boys and 12 girls. Most presented with nontender, palpable neck masses and minimal constitutional complaints. Adenopathy was unilateral in all cases but 2. Mycobacterium avium-intracellulare and M. fortuitum were the main causative organisms. All underwent excision of the affected nodes. Long-term follow-up has been uneventful, except for 1 case of local recurrence requiring re-excision.

This study emphasizes the marked variability in the clinical presentation of scrofula in children, stressing the importance of the differential diagnosis between tuberculous and atypical mycobacterial cervical lymphadenitis. The treatment of choice for the latter is complete excision of the affected nodes. Other treatment is followed by recurrence and unnecessary complications and should be avoided.

Physiological Aspects of Women in Combat

D. Libster, Y. Heled, Y. Shapiro, Y. Epstein

IDF Institute of Military Physiology and Heller Institute for Medical Research, Sheba Medical Center, Tel Hashomer

Since military service is physically demanding, soldiers must maintain high levels of physical fitness for optimal performance of their duties. Women are at a physiological disadvantage when competing against men: they have a smaller muscle mass, more body fat, lower red blood cell counts, lower hemoglobin levels and smaller cardiac outputs. Women are slower and weaker than men and more prone to exercise-induced skeletal injuries. Fewer women than men meet the standards of physically demanding jobs. Therefore integrating women into physically demanding military-oriented jobs requires redesigning or modifying the tasks (different pace, mechanical aids, teamwork). While physical training can increase the physical capacity of women, training cannot completely eliminate gender differences. Thus the data presented do not imply that women cannot be integrated into combat units, but highlight gender-related differences which might have an effect on the ability of women to compete equally with men at the same task.

ד. זלצר, י. שפירא, ש. ברלינר

מח' לרפואה פנימית ד' והיחידה לטיפול בנוגדי קרישה, מרכז רפואי סוראסקי תל-אביב והפקולטה לרפואה סאקלר, אוניברסיטת תל- אביב

Prevalence of Medical Complaints in the Community-Dwelling Elderly

J. Gindin, M. Geitzn, M. Dushenat, H. Siboni, D. Goldstein, Z. Shapira, N. Konstantin, A. Wurm, A. Goldsmid, E. Hay-Am

Geriatric Institute of Education and Research, Kaplan Medical Center, Rehovot; Pharmacology Dept., Kupat Holim Klalit, Tel Aviv and Central District; and Kupat Holim Klalit, Rishon LeZion

We assessed the prevalence of self-reported medical complaints among the community-dwelling elderly receiving regular medication, and determined associations between health and sociodemographic variables, and the prevalence of complaints.

The study included 170 patients, 60-90 years of age, living at home. Participants were recruited from the 3 main primary care clinics in Rishon LeZion. All were receiving chronic medication and were followed-up utilizing a long-term medication card. Data were gathered in interviews held in patients' homes using a structured questionnaire which included sociodemographics, diseases and medication, mental state assessment by Katzman's score, and a list of 15 medical complaints common among the aged. Relations to age, gender, education, living arrangements, number of diseases and number of medications per patient were determined.

Mean age of participants was 73.2±6.0 years and they suffered an average of 4.07±2.16 diseases and took 5.10±2.83 types of drugs. The most prevalent complaints were: weakness and fatigue (65.0%), agitation and restlessness (56.4%), dry mouth (45.6%), constipation (43.6%) and dizziness (43.2%). The number of diseases, gender, education and age had the strongest associations with the prevalence of specific complaints, as well as their total number. The association between number of medications and mean number of complaints was of borderline significance.

Video-Assisted Thoracoscopic Surgery for Diagnosis of Pulmonary Lesions

O. Zamir, Y. Haskel, R. Spira, D. Eimerl, H.R. Freund

Depts. of Surgery and Anesthesiology, Hadassah University Hospital, Mount Scopus, Jerusalem

23 patients (age 11-66 years) underwent video-assisted thoracoscopic biopsy for diffuse disease or peripheral nodular lesions of the lung. 12 had been previously treated for extra- pulmonary malignancy and lung biopsy was done for suspicious metastases. In all cases except 1, lesions were identified and biopsied by thoracoscopy. The postoperative course was easier and shorter as compared to thoracotomy and the mean hospital stay was only 2.5 days. Thoracoscopic lung biopsy is a safe, effective and accurate diagnostic modality for diffuse lung disease and peripheral lesions. It is associated with minimal postoperative pain and discomfort, short hospital stay, early return to normal activity, and gives good cosmetic results.

Atypical Infantile Hypertrophic Pyloric Stenosis

O. Eyal, A. Asia, U. Yorgenson, H. Nagar, Z. Schpirer

Pediatric and Pediatric Surgery Depts., Dana Hospital, Tel Aviv- Sourasky Medical Center, Tel Aviv

Infantile hypertrophic pyloric stenosis (IHPS) is the most common reason for nonbilious vomiting in infants. Its cause is unknown. Hypertrophy of pyloric muscle can progress after birth and reach complete gastric outlet obstruction. Usually symptoms start after the age of 3 weeks. In the past diagnosis was based on history of projectile, nonbilious vomiting and palpation of a pyloric mass. Greater awareness of IHPS and increased use of imaging modalities, mainly abdominal ultrasonography, have resulted in a change in the clinical condition at presentation. The length of illness before admission has decreased and weight loss, dehydration and metabolic abnormalities have become less common. We describe an atypical clinical manifestation of IHPS: bilious vomiting. This atypical presentation may be due to earlier diagnosis.