יורם מנחם ואלדד בן-שטרית

האגף לרפואה פנימית, בית החולים האוניברסיטאי והפקולטה לרפואה של האוניברסיטה העברית, הדסה עין-כרם, ירושלים

סקלרודרמה (טרשת העור) היא מחלה רב-מערכתית מגורם בלתי-ידוע, המתאפיינת בלייפת של העור, ובמעורבות כלי-הדם ואיברים ויסצראליים, כולל ריאות, כליות, לב ומערכת העיכול. באופן גס, מקובל למיין את הסקלרודרמה לשתי קבוצות עיקריות:

1)Diffuse cutaneous scleroderma – מחלה המתאפיינת בהתעבות סימטרית של העור המתהווה במהירות ומופיעה בגפיים, בפנים ובגו. ההתעבות היא בכל הגפיים ולא רק בחלק הרחיקני של הגף. חולים אלה נמצאים בסיכון גבוה ללקות במחלות כיליה ואיברים פנימיים אחרים.

2) Limited cutaneous scleroderma  - מחלה בה קיימת התעבות סימטרית של העור בעיקר בחלק הרחיקני של הגפיים ובפנים. לעיתים קרובות מאובחנים חולים אלה כלוקים בתסמונת CREST (קלצינוזיס, תופעת רנו, ליקוי בתנועתיות הוושט, סקלרודקטילי, וטלאנגיאקטזיה).

לחולים אלה בד"כ פרוגנוזה טובה, ורק מיעוטם ילקו ביתר-לחץ-דם ריאתי או צמקת המרה (biliary cirrhosis).

Sentinel Lymph Node Biopsy in Breast Cancer: A Validation Study and Preliminary Results

Aviram Nissan, Ram M. Spira, Roland Chisin, Oded Zamir, Diana Prus, Martin Klein, Mahmoud Badriyyah, Herbert R. Freund

Departments of Surgery. Biophysics and Nuclear Medicine, and Pathology. Hadassah University Hospital Mount Scopus and Hebrew University - Hadassah Medical School, Jerusalem

Introduction: Sentinel lymph node biopsy (SLNB) has been recently proven to be an accurate staging method for breast cancer, replacing axillary lymph node dissection (ALND) in selected cases. We present our initial experience and the process of introduction and implementation of SLNB in a University Hospital setting.

Material and methods: 46 SLNB were performed in 42 consecutive female patients with invasive breast cancer. Treatment included 0.4mCi-2mCi of Tc-99m rhenium colloid injected either 2 hours before surgery (0.4 mCi) or the night before surgery (2 mCi). Four milliliters of Patent Blue V were injected peritumoral 10 minutes prior to skin incision in all patients. Following SLNB all women underwent subsequent ALND. Sentinel nodes were processed both with multiple (10-15) H&E sections and immunohistochemistry with cytokeratin antibodies stain.

Results: Blue dye, isotope or the combination of both identified 43/46 (93%) of the sentinel lymph nodes. ALND was performed only unilaterally in 4 patients with bilateral breast cancer bringing the total evaluable SLNB to 39. In the 39 patients in whom the sentinel node was successfully identified and underwent ALND, the SLNB was true positive (TP) in 17/39 (44%) true negative (TN) in 20/39 (51%) and false negative in 2/39 [(5%), both T2 lesions] with overall accuracy of 95%. In the last 10 cases all sentinel nodes were successfully identified with 70% TP and 30% TN.

Conclusions: Experience with at least 30-40 consecutive cases for safe implementation of SLNB in clinical practice. Specific training and dedication is required for the entire team involved, including surgeons, nuclear medicine physicians and technicians and pathologists.  

ניר הוד (1), סיימון שטראוס (2), תפחה הורן (1),

המכון לרפואה גרעינית (1), והיחידה לעל-שמע (2), החטיבה לדימות, המרכז הרפואי "אסף הרופא", צריפין, הפקולטה לרפואה סאקלר, אוניברסיטת תל-אביב

קישריות בבלוטת התריס הניתנות למישוש קיימות ב-4% מהאוכלוסייה הבוגרת באזורים בהם צריכת יוד במזון מספקת; בחולים אלה נדרשת אבחנה מבדלת, על מנת לשלול בראש ובראשונה שאת ממאירה של בלוטת התריס. היארעות שאת ממאירה בבלוטת התריס מוערכת בכ-2 חולים מתוך אוכלוסיה של 100,000 אנשים מדי שנה. שאת ממאירה בבלוטת-התריס שכיחה יותר בנשים ובקרב בני-אדם שנחשפו לקרינה באזור הראש והצוואר; לעיתים רחוקות, מדובר בתיסמונת משפחתית (Men II).

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.

Screening for Early Detection of Prostatic Cancer

A. Neheman, Y. Shotland, Y. Metz, A. Stein

Dept. of Urology, Carmel Hospital, Lady Davis Medical Center, Haifa

Prostatic cancer (PC) is second only to lung cancer as a cause of cancer mortality in men word-wide. In Israel it is the most common cause of cancer mortality in men, after lung cancer and colo-rectal cancer.

We screened, for the first time in Israel, for prostatic cancer using serum levels of PSA and a digital rectal examination (DRE). The purpose was not only to diagnose PC but also to increase public awareness of the condition.

300 men in the Haifa area who met statistical criteria for early diagnosis of PC participated. They filled a questionnaire regarding risk factors for PC (age, family history (FH) of prostatic and breast cancer, cigarette smoking, alcohol consumption, previous PSA sampling) and were examined. Those who had out-of-ragne, age-related PSA values, or a pathologic DRE underwent trans-rectal ultrasound (TRUS) examination and guided biopsy of the prostate. Those with a positive biopsy for PC underwent radical prostatectomy or radiation therapy.

41 (14.3%) had out-of-range, age-related PSA levels and 10 (3.5%) had a pathologic DRE. 39 (13.3%) underwent TRUS and biopsy and 6 (2.04%) had clinically significant PC, all early stages (Gleason 4-6).

Correlation between age and PSA has been proven statistically significant (p<0.05). Symptoms of urinary tract obstruction and nocturia were related to a high PSA (p=0.035 and 0.002, respectively). Those with PC had at least 1 symptom of urinary tract obstruction; 6 (15.3%) who underwent TRUS and biopsy and a FH of prostate cancer. However, no subject with a FH of PC had biopsy-proven cancer. Those with PC had PSA values from 4.9 to 31.8 ng/ml (9.6 median). Age-related PSA had a positive predictive value of 17.1%.

Results of our annual screening for early detection of PC using age-related PSA, and DRE are encouraging: cases detected were clinically significant and treatable. It would appear that screening for PC will result in decreasing the incidence of metastatic cancer and therefore mortality. 
 

Dermatitis from Contact with Agave Americana

Haim Golan, Marina Landau, Ilan Goldberg, Sara Brenner

Dermatology Dept., Tel Aviv-Sourasky Medical Center

Various plants induce dermatitis in man. There have been only a few published cases of contact dermatitis caused by Agave americana (AA).

We report intentional exposure to AA in a soldier seeking sick leave, and review our previously reported cases. Treatment with oral antihistamines and topical saline compresses resulted in subsidence of the systemic symptoms within 24h and regression of cutaneous manifestations in 7-10 days.

Physicians should be alert to the possibility of self-inflicted contact dermatitis induced by exposure to plants, especially to A. americana. Systemic signs may accompany the cutaneous lesions.

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.

Follicular Splenic Lymphoid Hyperplasia Associated with EBV Infection

Boleslaw Knobel, Enrique Melamud, Sharon Nofech-Moses, Liliana Zeidel

Dept. of Medicine B and Institute of Pathology, Edith Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel Aviv University

Massive splenomegaly is defined as a spleen weighing about 10 times normal weight. We describe a 36-year-old man who had huge splenomegaly and secondary pancytopenia simulating malignant lymphoma for about 3 months. Splenectomy was necessary because of the suspicion of hematologic malignancy, especially isolated lymphoma of the spleen, and pain and mechanical abdominal disturbances.

On operation, the spleen was 25 cm long and weighed 250 g. There was florid, reactive follicular lymphoid hyperplasia. Immunohistochemical staining with CD-20(L26), CD-45Ro(UCHL), bcl-2 oncoprotein (Dakopatts), EBV (anti-EBV mol weight 60 KD, Dakopatts) was consistent with reaction to EBV infection and not with follicular lymphoma. Lack of PCR amplification using DNA extracted from paraffin-embedded splenic tissue indicated absence of a monoclonal B cell population carrying rearranged immunoglobulin genes. The lymphocytic population was proven polyclonal by the negative results of PCR for the bcl-2 gene rearrangement. EBV seroconversion from high titer antibodies of anti-EBV-VCA-IgM to negative, and from negative EBNA to positive was consistent with an apparent primary EBV infection.

We have not found on computerized search a previous report of reactive follicular splenic hyperplasia to EBV infection causing huge splenomegaly, with or without EBV-induced infectious mononucleosis.

Severe Heat Stroke in an Intensive Care Unit

Amir Halkin, Dina Lev, Oded Szold, Philip Bidermann, Sarah Bulocnic, Pinchas Halpern, Patrick Sorkine

Depts. of Medicine and Surgery, and Intensive Care Unit, Tel Aviv Medical Center

During the August 1998 heat wave in Tel Aviv we admitted many patients for acute heat-related illness; 6 had severe heat stroke and were admitted in critical condition. We describe their clinical courses during the first 5 days of hospitalization, including response to treatment and implications for future management of this disorder.

The mean APACHE II score of the 6 was 30±3.5 and mean Glasgow Coma Scale rating 3.5±0.5; they were in hypovolemic shock and respiratory failure, necessitating mechanical ventilation. Despite early effective therapy (core temperature in all was reduced to less than 398C in less than 1 hour), there was 1 death (mortality 15%) and 4 required further intensive care for life-threatening multiple organ failure.

During severe heat waves a significant number of referrals for acute heat-related illness must be anticipated, possibly overwhelming admission capacity of regional intensive-care units. Severe heat stroke complicated by multi-organ failure is not necessarily related to prior physical activity. Although important in determining prognosis, early treatment does not prevent severe complications. Mechanisms regulating body heat may remain disturbed for days following early treatment and apparent stabilization, mandating continued hospitalization.

Home Palliative Care of Terminal Cancer Patients, with Family Feedback

Hana Arad, Hana Geva, Valery Rosin, Ruth Kibrik, Isaac Kersz

Home Care Unit of Kupat Holim Haklalit, HaEmek Medical Center, Afula and Quality Improvement Unit, Rambam Medical Center, Haifa

Palliative care of terminal cancer patients is one of the tasks of our Home Care Unit. Increasing hospitalization costs have brought forward the decision to treat them at home, assuming that they would prefer to return and die in their natural surroundings, among family.

Most of our patients are aged, recent immigrants from the Soviet Union, of low socioeconomic status; most live with their close families. Our care model combines social, cultural, economic, medical and nursing aspects. More patients choose to die at home, and that is where costs are minimal. Care management and characteristics of 44 terminal cancer patients, who died between January and October 1996, are described. Living with a family was not required for treatment at home. Length of care by the unit ranged from 1-48 weeks, with an average of 8.5 and a median of 6. 55% of patients were hospitalized, most (58%) for 5-9 days for noncancerous diseases, and then discharged home. 54% died at home, a third were hospitalized for 2-17 days before death. Compared to the average length of stay in palliative care oncology wards, 1044 days and more than NIS 500,000 were saved.

A telephone survey examined families' satisfaction with various components of care. 92% were satisfied with the home treatment. 79%-82% felt that the nurse and doctor of the team met their needs and expectations. Half the families were satisfied with the treatment of pain. Families in which treatment was 24 weeks or more were generally less satisfied than those with shorter treatment at home. We learned that an early entry into treatment is necessary; hospital referral criteria should consider to a greater extent the coping ability of families; nursing aid hours should be increased and professional emotional support added; additional pain control methods should be used. All these would strengthen families, improve quality of care, and contribute to additional savings by decreasing hospital stay.

Acute Malaria in an Israeli Tourist to Kenya

Doron Zamir, Chen Zamir, Shimon Storch, Moni Litmanovich, Paltiel Weiner

Dept. of Internal Medicine A, Hadera Sub-District Health Office and Nephrology Dept. and Intensive Care and Infectious Disease Units, Hillel Yaffe Medical Center, Hadera

Malaria is 1 of the main causes of death in third world countries. It has become extinct in Israel and imported cases are rare, since most visitors to endemic countries take anti-malarial prophylaxis. We report an Israeli tourist to Kenya infected with falciparum malaria complicated by severe metabolic acidosis, renal failure and adult respiratory distress syndrome. After intensive care treatment this preventable condition improved.

Malignant Lymphoma of the Bladder

Y. Mor, Z. Dotan, J.H. Pinthus, I.S. Engelberg, J. Golomb, J. Ramon

Depts. of Urology and Pathology, Chaim Sheba Medical Center, Tel Hashomer

Urinary tract lymphoma is usually reported when the secondarily stem is affected by widespread non-Hodgkin lymphoma. We describe an 83-year-old woman who presented with secondary lymphoma of the bladder 3 years after diagnosis when it initially infiltrated her breast. Treatment included local transurethral excision followed by chemotherapy, during which she died of disseminated disease.

Intestinal Transplantation: World Experience and Future Perspective

Eytan Mor, Moshe Rubin, Yaron Niv

Depts. of Transplantation, Surgery B and Gastroenterology Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva

Intestinal transplantation, which until recently has been considered an experimental procedure, is now undergoing considerable change and becoming a standard treatment for patient with intestinal failure. The major improvement in results is due to the introduction of new immunosuppressive agents that have led to significant reduction in acute rejection. Nevertheless, reduction in severe infectious complications, which are the main cause of mortality after transplant, as well as improved techniques for early diagnosis of rejection are needed before intestinal transplantation can be widely used.

We describe our experience in post-transplant follow-up of a woman, aged 32-years, who had undergone intestinal transplantation for short bowel syndrome after extensive bowel resection.

Iatrogenic Gallstone Ileus: A New Complication of Bouveret's Syndrome

Miguel Iuchtman, Amos Sternberg, Ricardo Alfici, Ehud Sternberg, Tzvi Fireman

Depts. of Surgery and Gastroenterology, Hillel Yaffe Medical Center, Hadera, and Rappaport Medical School, Haifa

Bouveret's syndrome involves gastric outlet obstruction caused by a gallstone in the duodenum. This type of gallstone ileus can be diagnosed and treated endoscopically. Endoscopic stone removal is especially indicated in poor risk patients. A dislodged impacted stone can migrate distally and cause small bowel mechanical obstruction. We report a 51-year-old woman who underwent endoscopic duodenal stone manipulation which resulted in small bowel obstruction.

Methotrexate Treatment in Refractory Juvenile Rheumatoid Arthritis

R. Brik

Pediatrics B Dept., Rambam Medical Center, Haifa

The mean time from initiation of methotrexate (MTX) treatment of juvenile rheumatoid arthritis (JRA) to partial remission of clinical symptoms and total clinical remission was assessed. 9 girls and 8 boys, from 3 to 18 years of age (mean 11.4±5.4) with active JRA by American College of Rheumatology (ACR) criteria (5 systemic, 8 polyarticular and 4 pauciarticular disease onset), who failed to respond to adequate courses of non-steroidal anti-inflammatory drugs (NSAID), steroids or disease-modidrugs were studied.

Clinic visits were scheduled at monthly intervals for physical and laboratory assessment disease activity and drug safety. Partial response to MTX was defined a 25% reduction of the active joint count and/or articular severity score. Total clinical remission was defined as in adult rheumatoid arthritis. The duration of disease activity until enrollment ranged from 6 months to 14 years (4.5±3.7 yr); duration of therapy was 3 months to 3 years (14.6±9.3mo) and dosage ranged from 5 to 15 mg/m²/week. Prednisone in doses below 10 mg/day and NSAID were permitted.

14 of 17 patients (82%) had a 25% reduction in joint activity after 6 weeks to 4 months (9.2±3.2 weeks); 10 (59%) went into full clinical remission after 5 to 26 months (14.3±9 months); 3 relapsed after an initial response to treatment, and 4 (23%) did not respond to MTX. The non-responders were males who required higher doses of prednisone (p<0.0001).

MTX appears to be effective therapy for children with JRA. An initial response can be expected in most patients after 9 weeks of treatment, and full clinical remission occurs after a mean of 14 months.