רון בן-אברהם, דיאגו בלטרוטי, דוד ניב ואבי וינברום

מתן מישלב של אופיואידים בעלי זיקה שונה לקולטנים מסוג  ..........  הוכח כיעיל בהקלת כאב בחולדות. בעבודה זו, נבדקה בצורה כפולת-סמיות ההשפעה נוגדת הכאב הסב ניתוחי של מתן מורפין – אגוניסט טהור של הקולטן ........  ובופרנורפין – אגוניסט חלקי של הקולטן  ........  , בשלוש קבוצות של חולות (10 חולות בכל קבוצה) שעברו כריתת רחם בהרדמה כללית. המישלב התרופתי לשיכוך כאב במתן טרום ובתר ניתוחי כלל מתן תת-שידרתי של 0.3 מ"ג מורפין ותמיסת מי-מלח לתוך הווריד (קבוצה 1); מתן לתוך הווריד של 0.09 מ"ג בופרנורפין ומי מלח במתן תת-שידרתי (קבוצה 2); או מתן במישלב של מורפין ובופרנורפין במינונים שצוינו לעיל (קבוצה 3). קבוצה 3 קיבלה מינונים נישנים לתוך הווריד של בופרנורפין ומי-מלח במתן תת-שידרתי.

רמות הארגעה (sedation), החרדה והכאב, כפי שהוערכו על פי סולם מספרי או מדדי, היו שוות מיד לאחר הניתוח. אולם במדידה שנערכה 12 לאחר הניתוח, הודגמה דרגת ארגעה וכאב נמוכות באורח משמעותי בקבוצה 3 ובהשוואה לשאר הקבוצות. השפעת הבופרנורפין במינונים נישנים בקבוצה 3 היתה ממושכת יותר בהשוואה לקבוצה 2 (מתן לתוך הווריד ללא מישלב עם מורפין). שיעורי השפעות-הלוואי בקבוצות 2 ו-3 היו נמוכות ב-44% וב-42%, בהתאמה, בהשוואה לאלה שאובחנו בקבוצה 1. לא אובחנו סימני גמילה מערכתיים. לפיכך, מישלב של מורפין תת-שידרתי ומינון נמוך של בופרנורפין לתוך הווריד פועל כמשכך-כאב טוב יותר, ממושך יותר ועם שיעור נמוך יותר של השפעות-לוואי בהשוואה לנשים שעברו כריתת-רחם וקיבלו מורפין בלבד, במתן תת-שידרתי.

אהוד ברגר, רוני שילה, אברהם ויצמן, חנן מוניץ

המח' לבריאות הנפש א' ויחידת המחקר, המרכז לבריאות הנפש גהה

סכיזופרניה היא מחלה הטרוגנית עם מיגוון תסמינים רחב, ללא אטיולוגיה ברורה או אחידה. במהלך השנים, הועלו תיאוריות שונות בניסיון להסביר את ההסתמנות בסכיזופרניה באמצעות דגמים שונים, ומרביתם מבוססים על הפרעה בפעילות מרכזית של נירוטרנסמיטרים שונים, במיוחד דופאמין, סרוטונין וגלוטמאט.

בתחילה שלטה התיאוריה הדופאמינרגית שהניחה, כי קיימת פעילות-יתר דופאמינרגית במוח בחולים בסיזופרניה, במיוחד גירוי עודף של קולטנים מסוג D₂, בעיקר במסלולים מזולימביים ומזוקורטיקליים.

The Interaction Between Saliva and Cigarette Smoke and its Devastating Biological Effects as Related to Oral Cancer

Rafael M. Nagler, Ifat Klein, Abraham Z. Reznick

Department of Oral & Maxillofacial Surgery, Salivary Clinic and Oral Biochemistry Laboratory and Department of Anatomy and Cell Biology, Rambam Medical Center and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel

Saliva is the first body fluid to confront inhaled cigarette smoke (CS) which is injurious to the oral cavity and is associated with several oral diseases and cancer. We have recently demonstrated in an In vitro model that an exposure of saliva to nine `puffs' of CS induced a distinct increase in protein carbonyls. This elevation of protein carbonyls caused by CS may be the result of aldehydes presented in the CS reacting with sulphydryl (-SH) groups of the proteins. Moreover, following the exposure to CS, the activities of several salivary enzymes amylase, lactate dehydrogenase (LDH) and acid phosphatase (ACP) were found to be significantly reduced by 83%, 57% and 77%, respectively. However, CS had no effect on the activities of aspartate aminotransferase and alkaline phosphatase. In the current study we found that CS also reduced salivary peroxidase activity by no less than 80% which may be of a great importance to the clinical set up as peroxidase is considered a pivotal enzyme of the the salivary protecting system. Furthermore, in contrast to LDH findings in saliva, the LDH activity in plasma was not reduced following its exposure to CS.

Conclusion: Hence, we concluded that the loss of salivary enzyme activities may be due to various agents in the CS that affect the enzyme via different mechanisms.

Surgery of the Carotid Body Tumors

Galit Sivak, Menashe Haddad, Ram Avrahami, Avigdor Zelikovski

Department of Vascular Surgery, Rabin Medical Center - Beilinson Campus, Petah-Tikva and the Sackler School of Medicine, Tel-Aviv University, Israel.

Carotid body tumor is a rare tumor of obscure origin, usually benign, and commonly present as a non-painful cervical mass. Resection is the treatment of choice. When the tumor is very adherent to the carotid artery, it may be necessary to also resect the artery and to reconstruct the arterial continuity using a saphenous or synthetic interposition graft. The most common complication of surgery is damage to the cranial nerves in the vicinity of the artery. We present 8 patients with carotid body tumor who underwent surgery in our department in 1996-1999. Two had a large tumor penetrating the intima which mandated resection of the involved carotid artery and a saphenous interposition graft reconstruction. Our experience with resection of carotid body tumors is detailed, with emphasis on precautions taken to prevent damage to the adjacent cranial nerves.

Treatment of Traumatic False Aneurysm of the Thoracic Aorta with Stent Graft

R. Avrahami, M. Noyman-Levine, M. Haddad, A. Koren, J. Dahan, G. Sivak, A. Zelikovski,

Department of Vascular Surgery, Rabin Medical Center, Beilinson Campus, Petah Tikva

and Sackler School of Medicine, Tel-Aviv University, Israel

The treatment of traumatic false aneurysm of the thoracic aorta by endovascular stent graft may have advantages over conventional surgery. This is a case study of two women suffering from false aneurysm of the thoracic aorta caused in one by a knife injury and in the other by a car accident. After the patients became hemodynamically stable, a commercially available endothelial stent graft (Talent, Gor) was deployed. Recovery was rapid in the first patient. The second patient required emergency laparotomy for venous bleeding one day after stent placement; she died two weeks later, mainly from organ failure.

Conclusions: Endovascular techniques can be used in selected cases to treat thoracic false aneurysms thereby avoiding the complexity and morbidity of conventional surgery.

Aggressive Surgical Treatment for Cholangiocarcinoma

M. Shimonov, P. Schecter, Y. Avni¹, E. Rabin², A. Rosen, A. Czerniak,

¹Department of Surgery A, Gastroenterology and ²Invasive-Radiology, Wolfson Medical

Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel

Surgery remains the only curative approach to cholangiocarcinoma. Despite operative difficulties concerning tumor location, vascular involvement or hepatic invasion curative resection (i.e. achievement of tumor free margins) carries good survival rates and is associated with low morbidity and mortality. Our experience with 31 patients with cholangiocarcinoma operated during the years 1993-1999 is presented.

Twenty-five patients were found to have hilar cholangiocarcinoma, 3 carcinoma of mid-choledochus and 3 distal cholangiocarcinoma. All patients were evaluated by a diagnostic protocol including laparoscopy and laparoscopic ultrasound. Surgery consisted of local resection of the tumor with Roux en Y hepaticojejunostomy reconstruction. Three patients had concomitant hepatic resection for hilar cholangiocarcinoma while 3 patients had pancreaticoduodenectomy for distal cholangiocarcinoma. Adenocarcinoma was diagnosed in all patients. Curative resection was achieved in 19 patients and palliative resection (microscopically involved resected margins) in 12. One patient died at 60 days postop (3.5% mortality). Postoperative complications included cholangitis occuring in 10 patients who were referred with biliary drains, intraabdominal abscess (2 patients) and biliary leakage (1 patient) all treated conservatively.

Overall survival rate was 82% at one year, 73% at two years and 45% at 5 years. When comparing curative resection with palliative resection, survival rates were 92% versus 71% for 1 year, 72% versus 50% for 2 year and 57% versus 14% for 5 years.

Selection of patients using Laparoscopic Ultrasound combined with aggressive surgical approach enable curative or palliative resection 15 the only treatment modality which is significantly improved survival.

Antidepressive Effect of Pyridoxine (Vitamin B₆) in Neuroleptic-Treated Schizophrenic Patients with Co-Morbid Minor Depression - Preliminary Open-Label Trial

Roni Shiloh¹, Abraham Weizman¹, Nechama Weizer¹, Pnina Dorfman-Etrog¹, Hanan Munitz¹ 

¹Geha Psychiatric Hospital, Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Petah Tikva; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Background: Minor depression is reported in 20-60% of schizophrenic patients during various stages of their disorders; impairing patients' compliance, response to treatment and worsening their overall prognosis. Various anti-depressive treatments have been proposed for such cases but response rates are usually poor. Pyridoxine (Vitamin B⁶) in essential for the proper metabolism of various neurotransmitters that are considered relevant to the pathophysiology of depression and/or schizophrenia and it has been reported beneficial in ameliorating depressive symptoms as part of major depression, premenstrual syndrome or 'Chinese restaurant syndrome'. We hypothesized that addition of pyridoxine to on-going neuroleptic treatment could improve minor depression in schizophrenic patients.

Method: Nine schizophrenic patients with co-morbid minor depression participated in this study. All participants had a stable unchanged clinical state (changes in Brief Psychiatric Rating Scale (BPRS). Scale for the Assessment of Positive Symptoms (SAPS), and Scale for the Assessment of Negative symptoms (SANS) scores <5%) and all were maintained on unchanged doses of anti-psychotic drugs for at least 4 consecutive weeks prior to initiation of the study.

Participants received, open-label, pyridoxine 150 mg/day in addition to their anti-psychotic treatment for 4 consecutive weeks. Mental status was evaluated before, during, and at the end of 4 weeks of pyridoxine administration using the BPRS, SAPS, SANS and HAM-D.

Results: Two of the nine patients (22%), characterized by higher initial HAM-D and SANS scores, and by older age and longer duration of illness, experienced marked improvements in depressive symptoms (23% and 28% decrease in HAM-D scores) following 4 weeks of pyridoxine administration. In one of these two, the improvement in depressive symptoms was accompanied by a parallel decrease in SANS Scores.

Conclusion: A subgroup of schizophrenic patients with co-morbid minor depression may benefit from pyridoxine addition to their on-going anti-psychotic treatment.

יורם אברהמוב

המח' לרפואת נשים ויולדות, המרכז הרפואי הדסה עין-כרם, ירושלים

טיפולי השראת ביוץ באמצעות גונאדוטרופינים מלאכותיים הביאו למהפכה של ממש בטיפולי הפוריות בשנים האחרונות, בכך שהעלו בהרבה את הסיכוי להרות, בעיקר בנשים עם הפרעות בביוץ, אך גם בנשים הלוקות באי-פוריות מגורמים אחרים, כגון עקרות בלתי מוסברת או עקרות הגבר. בנוסף מהווים הגונאדוטרופינים המלאכותיים מרכיב הכרחי בטיפולי ההפריה החוץ-גופית. אחד הסיבוכים היאטרוגנים הקשים של טיפולי השראת ביוץ בכלל ובגונאדוטרופינים בפרט הוא תיסמונת גריית-היתר של השחלות (ovarian hyperstimulation syndrome). תיסמונת זאת, על אף היותה נדירה, גורמת למירב התחלואה והתמותה הקשורות בטיפולי פוריות. התיסמונת מתבטאת בהגדלת השחלות, בחדירות-יתר של נימיות הדם עם דליפת נוזל למדור השלישי ובריכוז-יתר של הדם (hemoconcentration).

Selective Embolization of Hepatic Arteries in the Management of Severe Liver Trauma

Avraham Yitzhak¹, Gadi Shaked², Liliana Lupu³, Soli Mizrahi, Yoram Kluger⁴

¹Department of Surgery A, ²Trauma Service, ³Interventional Radiology, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, and Trauma Service⁴, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel

Two cases of severe hepatic injury in which selective hepatic artery embolization was used to control hemorrhage are presented. The first case is that of a 35 year old patient who sustained a severe liver injury after a car accident. A CAT scan of the abdomen revealed an AAST grade 5 liver injury, pooling of contrast material within the liver parenchyma, and blood within the peritoneal cavity. The patient was given fluid resuscitation and taken to angiography where bleeding from branches of the right hepatic artery was demonstrated. While angiography was being undertaken the hemodynamic status of the patient deteriorated, blood transfusion was started, and a selective embolization of the right hepatic artery was performed. The bleeding stopped promptly and hemodynamic stability was regained.

The second case is that of a 40 year old pedestrian run over by a car. Abdominal ultrasound revealed free fluid in the peritoneal cavity and the patient was rushed to the O.R. Crushed right lobe of the liver, and inferior vena cava and bowel tears were found. After perihepatic packing and resection of the right and sigmoid colons retrohepatic vena cava tear was repaired and perihepatic packing restored. The abdominal cavity was closed and the patient was taken to the ICU for the correction of hypothermia, metabolic acidosis, and coagulopathy that had developed during the surgery. After 8 hours in the ICU the patient was transferred for angiography and a selective embolization of branches of the right hepatic artery was performed.

The clinical course of the patients after angiographic embolization of the hepatic arteries is described and the literature that discusses the use of angiography and embolization of hepatic arteries after traumatic hepatic bleeding is reviewed.

אורי שולמן, רם סילפן, אברהם אמיר, דניאל האובן

המח' לכירורגיה פלסטית והיח' לכוויות, קמפוס בילינסון, מרכז רפואי רבין, פתח-תקווה

מלאנומה ממארת של העור (ממ"ע) היא שאת ששיעור היארעותה עולה בקצב מהיר בעולם כולו והיא מהווה אתגר טיפולי נרחב. כיום, הניתוח הוא הטיפול העיקרי בממ"ע, ואם השאת מאובחנת ומטופלת בשלב מוקדם, לפני חדירה עמוקה לשיכב הדרמיס, היפגעות קישיות לימפה והתהוות גרורות מרוחקות, הרי שסיכויי ההישרדות גבוהים.

ממ"ע באזור ראש-צוואר המתהווה בשכיחות של כ-20% מתוך כלל החולים במלאנומה ממארת, שונה במספר מובנים מאשר באזורים אחרים בגוף: כריתה נרחבת של השאת מוגבלת בגודלה עקב המיקום האנטומי באזור ראש-צוואר, הניקוז הלימפטי עשיר ביותר, ההשלכות האסתטיות עלולות להיות מרחיקות לכת וההשפעות התיפקודיות יכולות להיות בלתי הפיכות.

ממ"ע באזור ראש-צוואר מתרחשת בשכיחות שווה בנשים ובגברים. השאת ממוקדת בעיקר בפנים, ובשכיחות יורדת באזור הצוואר, הקרקפת והאוזניים.

קיימים מספר גורמי סיכון להתהוות מלאנומה ממארת בכל אזורי הגוף, ביניהם אנשים עם שומות מלאנוציטיות מרובות, שומה מלידה גדולה בקוטר מעל 20 ס"מ (giant congenital nevi), שומה דיספלסטית (dysplastic nevi) בעלי עור, עיניים ושיער בהירים עם נטייה להיכוות לאחר חשיפה קצרה לקרני השמש, בעלי עור עם נמשים, אנשים שנחשפו רבות לקרני השמש במהלך חייהם, אנשים בעשור החמישי לחייהם ואילך, אנמנזה משפחתית של מלאנומה ממארת המגבירה את הסיכון ללקות במחלה בשיעור של פי 2-8, אנמנזה של סרטני עור בעבר ואנשים עם דיכוי המערכת החיסונית. הסיכון במהלך החיים להתהוות מלאנומה ממארת בפעם השנה הוא 1%-8%.

Aggressive Surgical Approach in Pancreatic Cancer - Is it Justified?

V. Catz-Snir, P. Schachter, M. Shimonov, Y. Avni, G. Gvirtz, A. Czerniak

Depts. of Surgery, Gastroenterology, and Diagnostic Radiology, Wolfson Medical Center, Tel Aviv and Sackler Faculty of Medicine, Tel Aviv University

Resection presents the only possible cure for pancreatic cancer. An aggressive surgical approach may extend the limits of resection and offer cure for more patients. 37 women and 28 men, mean age 67 years (range 33-84) with focal lesions underwent pancreatic resection (1993-1999). Cancer of the pancreatic head was found in 45, in the ampulla in 4 and in the body or tail in 16. There was a tumor larger than 5 cm in 9, vascular involvement in 8, and a combination of both in 6.

All were evaluated prior to exploration by standard imaging techniques and 44 by laparoscopic ultrasound. 42 underwent pancreatico-duodenectomy, 16 distal subtotal pancreatectomy and 3 local excision of an ampullary tumor. Benign lesions were found in 8 (focal pancreatitis in 4 and a serous cystic lesion in 4).

Curative resection (microscopically negative margins, negative lymph nodes) was achieved in 44. 2 died 1-2 months after operation of septic complications (2% operative mortality). The most frequent complication (in 8) was pancreatic fistula. Additional complications included anastomotic-line bleeding (3), intra-abdominal abscess (2), and 1 developed portal vein thrombosis (treated surgically).

1- and 2-year survival in those after curative pancreatic resection was 81% and 55% respectively. 2-year survival in those after palliative resection (positive resection margins or positive lymph nodes) was 50% and 11%, respectively.

After proper selection of those in whom it is possible to perform curative resection, regardless of size or vascular involvement, an aggressive surgical approach is justified.
 

Long-Term Sequelae of Malignant Tumors in Childhood

N. M. Peretz, H. Goldberg, A. Kuten, I. Meller, E. Krivoi, A. Lorber, L. Bentur, A. Lightman, V. Gorenberg, M. Ben Arush-Weyl

Pediatric Hematology-Oncology Dept., Oncology Center, Pediatric Cardiology Unit, Pulmonology and Gynecology Depts., and Pediatric Endocrinology Unit; Rambam Medical Center and Technion-Israel Institute of Technology, Haifa; and Orthopedic-Oncology Unit, Tel Aviv-Sourasky Medical Center and Tel Aviv University

110 children with malignant diseases (leukemia excepted) who survived 5-20 years (median 9) post-therapy were followed (1996-1998). Median age during follow-up was 15 years (range 5-23). The most common malignancies were brain tumors, lymphoma, retinoblastoma and Wilm's tumor.

The 174 late side-effects included endocrine disorders (19%), cognitive impairment (14%), orthopedic dysfunction (12%), alopecia (12%), dental damage (11%), psychological (8%) and neurological (8%) disturbances, and azoospermia or amenorrhea (5%). There was no cardiac or renal damage and no second malignancy.

29% of side-effects were severe. There was significant reduction in quality of life in 54 (49%), in 27 of whom it was severe enough to require psychological intervention. Treatment of brain tumor caused 98 late side-effects in 28 patients (sequelae-to-patient ratio [SPR] 3.3). Most cognitive, endocrine and neurological disorders, and most cases of alopecia, dental and psychological difficulties were in these patients. There were frequent late complications in those treated for retinoblastoma (SPR 1.8), and bone or soft tissue sarcomas (SPR 0.8). Those treated for Wilm's tumor had few side-effects (SPR 0.4).

Late side effects were most frequent after radiation, reaching as high as SPR 2.4. It averaged only 0.5 in those treated with chemotherapy alone or in combination with surgery.

Reduction of late side-effects in these patients requires using less toxic modalities, as long as cure rate is not compromised. When considering secondary strategies, screening for early detection of late complications would enable immediate solutions, such as hormonal replacement or providing compensating skills for post-treatment disability.
 

Antioxidant Profile of Human Saliva and its Biological Significance

R. M. Nagler, A. Z. Reznick

Dept. of Oral and Maxillofacial Surgery, Salivary Clinic and Oral Biochemistry Laboratory; Rambam Medical Center and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

Saliva is the first biological medium to come in contact with materials entering the body through the oral cavity. These materials are contained in food and drink (or inhaled as volatile ingredients). Accordingly, saliva contains various defense mechanisms which have been thoroughly investigated. They include immunological and enzymatic systems aimed at pathological microorganisms. Saliva also can protect the mucosa against mechanical insults and when required, promote its healing via agents such as the epidermal growth factor.

Another defense mechanism in saliva which has been gaining increased attention and seems to be of paramount importance is its antioxidant system. We discuss both the molecular and enzymatic components of the salivary antioxidant system in respect to mixed, parotid, submandibular and sublingual saliva and under various physiological conditions of secretion.

Preservation of the Larynx in Advanced Cancer

Edward Rosenblatt, Nava Siegelmann-Danieli, Jemal Zidan, Nisim Haim, Abraham Kuten

Oncology Dept., Rambam Medical Center and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

The effectiveness of sequential chemo-radiotherapy in preserving the larynx in advanced laryngeal carcinoma was assessed. 4 Unselected patients (19 men and 2 women, mean age 60 years) with advanced squamous cell carcinoma of the larynx (T3-4/N0-3) received induction chemotherapy consisting of 2-3 cycles of cisplatin (100 mg/m²) and 5-flourouracil (1000 mg/m²/day) as a continuous infusion on days 1-5 followed by definitive radiotherapy: 50 Gy to the whole neck, 70 Gy to the larynx and clinically involved nodes, using a combination of 6 MV photons and 9-12 MeV electrons.

19 of The 21 patients responded to combined therapy but there was no response to induction therapy in 2 (10%) and 2 did not complete therapy due to severe toxicity. At a mean follow-up of 40 months, 7 had undergone total laryngectomy (33%), for an overall 5-year laryngeal preservation rate of 66%. Reasons for total laryngectomy in 2 patients were no response and in 5 tumor recurrence.

Mean survival was 39 months (range 11-46 months); at last follow-up 17 of 21 were alive and disease-free, 11 of whom had a functional larynx (65% of survivors). 2 died due to disease progression and 1 due to a cardiovascular event. Sequential chemo-radiation allows laryngeal preservation in about 2/3 of surviving patients without compromising survival.

Ent of Femoral Artery Pseudo-Aneurysms 

G. Szendro, A. Klimov, A. Lennox, B. Jonathan, L. Avrahami, B. Yechieli, M. Griffin, S. Yurfest, Y. Charach, L. Golcman, A.N. Nicolaides

Vascular Surgery Dept., Soroka Medical Center, Beer Sheba; Irvine Laboratory for Cardiovascular Investigation and Research, St. Mary's  Hospital, Imperial College Medical  School, London; Vascular Laboratory, Soroka Medical Center, Beer Sheba; and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

The femoral artery remains the most used peripheral site for radiological catheter access. With a greater number of both diagnostic and therapeutic procedures being performed by interventional radiologists and cardiologists, and with larger catheters being used for stenting and endovascular grafting, the incidence of iatrogenic pseudo-aneurysms reported has reached as high as 0.5-2%. Ideally, they should thrombose spontaneously. However, when this does not occur, management options include: observation, ultrasound-guided obliterative compression, direct thrombin injection, embolization, stent graft insertion, and very rarely- surgery.

During a 7-year period (1992-1999) we treated 131 cases of femoral artery false aneurysms. Until 1998 ultrasound-guided compression-obliteration, with a 95% success rate, was our method of choice. Since 1998, direct thrombin injection, with 100% success in 24 cases, has become our preferred method. It is pain-free, fully successful even in anticoagulated patients, and is currently our treatment of choice.