איתן ישראלי

המכון למחקר ביולוגי בישראל, נס ציונה

פרס נובל בפיסיולוגיה או ברפואה לשנת 2000 הוענק במשותף לשלושה חוקרים: ארביד קרלסון, פול גרינגארד, ואריק קנדל, על תגליותיהם בשטח "העברת אותו במערכת העצבים".

במוח האדם יש יותר ממאה מיליארד תאי עצב, המחוברים ביניהם ברשת ענפה ואינסופית של חיבורים. העברת אותות בין התאים נעשית בתיווך של חומרים כימיים, המגשרים על הסינפסות המפרידות בין התאים. לכל תא יכולות להיות אלפי נקודות מגע כאלה עם תאי עצב אחרים. שלושת חתני הפרס גילו תגליות חשובות הקשורות בהעברת האותות בין התאים בתהליך שנקרא העברת אותו איטית. תגליות אלה היו חיוניות להבנת התיפקוד הטיבעי של המוח, וכיצד הפרעות בהעברת אותו אלו עלולות לגרום למחלות במערכת העצבים ולמחלות נפש. בצד מימצאים אלה, פותחו תרופות לטיפול בהפרעות כנ"ל.
 

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.

Laparoscopic Adrenalectomy 

G. Zamir, D. Hazzan, D.J. Gross, S. Lyass, O. Jurim, E. Shiloni, P. Reissman

Depts. of Surgery, Endocrinology and Metabolism, Hadassah University Hospital, Ein-Kerem, Jerusalem

Constant advances and increasing experience in laparoscopic surgery renders it applicable for adrenal surgery. The wide exposure required for open adrenal surgery makes this minimally invasive procedure an attractive and advantageous alternative.

Between 1996-1999, we performed 35 laparoscopic adrenal-ectomies in 30 patients 20-72-years old. Indications included: Conn's syndrome - 14, pheochromocytoma - 11, Cushing's syndrome - 6, nonfunctioning adenoma - 3, and metastatic sarcoma - 1.

5 underwent bilateral laparoscopic adrenalectomy. In 3 (8.5%) the procedures were converted to open operations. Overall morbidity was 13% and there was no mortality. Mean operative time was 188 minutes, but only 130 in our last 10 cases. Mean hospital stay was 4 days and they returned to normal activity an average of 2 weeks later.

According to our study and previous reports, laparoscopic adrenalectomy is feasible and safe and it may soon become the procedure of choice for adrenal tumors.

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.

Liver Surgery - Five Years of Experience

Franklin Greif, Moshe Rubin, Eitan Mor, Israel Nudelman, Arnold Sihon, Arie Figer, Alex Belinki, Shlomo Lelcuk

Hepatobiliary Unit and Depts. of Surgery B, Transplantation, Oncology and Radiology, Rabin Medical Center (Beilinson Campus) and Sackler School of Medicine, Tel Aviv University

Major hepatic resections have been associated with significant morbidity and mortality. In the past decade or so this has changed and such procedures are now done in increasing numbers. In the past 5 years we operated on 129 patients with benign or malignant hepatic lesions (75 females, 54 males; age-range 14-84). the reason for surgery was malignancy in 94 (72.9%) and benign lesions in 35 (27.1%). The most common indication for surgery was liver metastases secondary to colorectal cancer in 45% of all patients or 61.7% of those operated for malignancy. Primary liver cancer was the cause for liver resection in 13.2% of all patients or 18.1% for those with malignancy. Of the 35 patients with benign lesions the leading causes for surgery included: giant cavernous hemangioma, simple liver cysts, echinococcus cysts and focal nodular hyperplasia (11%, 22.8%, 20% and 14.3%, respectively).

76 patients underwent anatomical resection and 63 had either a nonanatomical resection or a different operation. Among the former the most common procedure was right hepatectomy (36) and among the later a nonanatomical resection equal to 1-3 Couinod segments (44). Operating time ranged from 55 min. to 8:41 hours with a mean of 3:31‏1:37. Mean hospital stay was 8.7‏5.8 days and 86.8% received between 0-2 units of blood. Overall mortality was 6.2% and 31.2% of the fatalities had cirrhosis. Overall mortality in noncirrhotic patients was 2.6%. The complication rate was 16.3% and only 7 patients (4.4%) were hospitalized in the intensive care unit. This indicates that major liver resections can be done safely, with morbidity and mortality similar to that of other major abdominal operations. 

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.

Urgent, Unscheduled Self-Referrals by Ambulatory Patients

S. Vinker, S. Nakar, Z. Alon, H. Abu-Amar, G. Sadovsky, E. Hyam

General Sick Fund, Central District and Dept. of Family Medicine, Sackler Faculty of Medicine, Tel Aviv University

Direct self-referral to a consultant is common in the Israeli health system. Yet patients' reasons for their urgent, unscheduled self-referrals for ambulatory consultations (UUSR) have not been explored. We studied such consultations in an urban multi-disciplinary consultation center serving a population of approximately 100,000. Over a 3-month period such consultations in ophthalmology, ear-nose-and-throat and dermatology clinics were treated by a duty family physician (FP). The FP was instructed to focus on the urgent complaint and either to give definitive treatment and schedule a consultation when needed, or refer the patient for immediate specialist consultation. Patients treated by the FP were asked to fill an anonymous questionnaire, which 347/645 (55.4%) did.

Among the reasons for UUSR were that the patient thought that his/her complaints should be treated by a consultant (29%), the patient was sent by the FP without a consultation note (13.9%), the FP was not available (10.4%), or the patient wished to see the consultant for a second opinion (8.2%). In only 7.8% had the patient noted that his complaint needed urgent consultation. Duration of complaints, but not prior efforts to schedule a consultation, were associated with different reasons for asking for an UUSR. For various reasons patients preferred an UUSR rather than seeing their own FP. Patients' opinions regarding self-referrals are important in planning primary care facilities and FP training.

Abnormal Liver Function Tests in the Primary Care Setting

Shlomo Vinker, Sasson Nakar, Emanuel Nir, Eitan Hyam, Michael A. Weingarten

Dept. of Family Medicine, Rabin Medical Center, Sackler Faculty of Medicine; Tel Aviv University; and General Sick Fund, Central District

Results of laboratory tests ordered during a primary care encounter may reveal findings of abnormal liver function tests, including elevated liver enzymes, hyperbilirubinemia, hypoalbuminemia or abnormal coagulation tests. The object of this study was to describe the spectrum of these liver function test (LFT) abnormalities in primary care.

Results of all laboratory tests ordered during 10 months in an urban primary care clinic were retrospectively reviewed and the medical charts of patients with abnormal LFTs were studied. In 217/1088 (20%) of the tests at least 1 LFT abnormality was found in 156 patients. New diagnoses were made in 104 patients. The main diagnostic groups were: non-alcoholic fatty liver changes, Gilbert's disease, acute infectious hepatitis, alcoholic liver disease and cirrhosis and hepatotoxic drug injury. In 60 patients the physician classified the abnormality as negligible and not associated with significant disease. However, an abnormal test that had been ordered for evaluation of a specific complaint, was indeed likely to represent significant disease (X²=29.5, p<0.001). We conclude that finding abnormalities in liver function tests is common in the primary care clinic but does not often indicate significant liver disease.

Oncogenetic Counseling and Genetic Testing of Those at High Risk for Breast and Ovarian Cancer

Livia Theodor, Ronit Shiri-Sverdlov, Galit Hirsch Yechezkel, Revital Bruchim Bar-Sade, Eva Gak, Irit Friedman, Anna Kruglikova, Gilad Ben-Baruch, Shulamit Risel, Moshe Z. Papa, Boleslav Goldman, Eitan Friedman

Oncogenetics Unit, Dept. of Clinical Epidemiology, Institute of Genetics, and Gynecology, Oncology, and Surgical Depts., Chaim Sheba Medical Center, Tel Hashomer

There is inherited predisposition to breast and ovarian cancer in 5-10% of all women with these diseases. Germline mutations in BRCA1 and BRCA2 presumably account for most of the genetically susceptible individuals. We summarize 2 years of experience in counseling and testing for inherited predisposition to these cancers.

597 women (from 320 families) have been evaluated since August 1995. 242 were evaluated for inherited predisposition to breast and ovarian cancer. One-third had clear-cut evidence of familial background. 74 families were of Ashkenazi origin; the age range of breast cancer was 30-35, of ovarian cancer 40-45. In 80% of families other cancers were also noted in first degree family members, including lung, colon, and prostate cancer and leukemia.

Genetic testing revealed that 45% of affected and 25% of unaffected women were carriers of a mutation in BRCA1 or BRCA2: 67/90 185delAG (BRCA1), 12/90 6174delT (BRCA2), and 4/90 of 5382insC (BRCA1). In addition, a novel mutation in exon 11 of BRCA1 was detected, carried by 7/90 women. The experience gained in oncogenetic counseling and genetic testing for inherited cancer predisposition will eventually enable determining an optimal, rational therapeutic regimen in carriers of mutations.

Hepatocellular Damage after Using Ecstasy

E. Shiloach, E. Zecler, M. Horowiz, E. Scapa

Depts. of Medicine C and Gastroenterology, Assaf Harofeh Medical Center, Zerifin (Affiliated with Sackler Faculty of Medicine, Tel Aviv University)

Ecstasy is a stimulant used mainly by youngsters to get 'high.' There are few reports of acute injury of the liver due to ecstasy. We describe a 37-year-old woman who presented with the clinical picture of recurrent hepatitis following ingestion of the drug. After several months she developed liver cirrhosis shown by biopsy and CT scanning. This case emphasizes the potential danger of ecstasy. Every patient with hepatitis of unknown origin must be questioned about ingestion of the drug.

Stromal Uterine Sarcoma arising from Intestinal Endometriosis after Abdominal Hysterectomy and Salpingoophorectomy

Munir Bishara, Eitan Scapa

Institute of Gastroenterology, Hepatology and Nutrition, Assaf Harofeh Medical Center, Zerifin (Affiliated with the Sackler Faculty of Medicine, Tel Aviv University)

The incidence of ectopic endometriosis is 4% to 18%. The intestinal type is quite common with the rectosigmoid the most likely part of the bowel to be involved due to its pelvic location. A 43-year-old woman, whose symptoms, X-ray and endoscopic findings suggested malignancy of the rectosigmoid, is presented. Primary malignancy of the bowel was excluded by endoscopic biopsies. Histological examination at operation showed stromal sarcoma of the uterus with foci of endometriosis. There is no report in the English literature of transformation of intestinal endometriosis into malignancy, such as stromal sarcoma of the uterus, which imitates a primary malignancy with obstruction of the rectosigmoid.

Budd-Chiari Syndrome

S. Goland, S.D.H. Malnick, L. Shvidel, E. Mor, Z.M. Sthoeger, E. Evron

Medical Depts. C and B, and Hematology Institute, Kaplan Hospital, Rehovot; and Surgical Dept. B, Rabin Medical Center, Beilinson Campus, Petah Tikva

Budd Chiari syndrome is a rare disorder resulting from occlusion of hepatic venous drainage by hepatic vein thrombosis or by a membranous web in the inferior vena cava. In western countries the commonest causes are myeloproliferative disorders and hypercoagulable states. Presentation may be acute with rapid accumulation of ascites and hepatic failure, or subacute with symptoms developing over a few months. A chronic progressive form has also been described. On presentation there is usually abdominal pain, ascites, and hepatosplenomegaly; hepatic encephalopathy is found in about a third. Noninvasive, ultrasound-Doppler is recommended in diagnosis, and has a high correlation with hepatic venography. Liver biopsy is required for therapeutic decisions. Those with advanced hepatic failure or severe fibrosis on liver biopsy are referred for hepatic transplantation. When biopsy shows only hepatic congestion and inflammatory infiltrates, portosystemic shunting is recommended. We present a 61-year-old woman with ascites and hepatosplenomegaly that had developed over the courses of a few months. Budd-Chiari syndrome with chronic myelofibrosis and congenital protein C deficiency were diagnosed. Portosystemic shunt was performed but death from sepsis followed shortly.

Oral Anticoagulation Therapy in the Primary Care Setting

Shlomo Vinker, Sasson Nakar, Sergei Finkel, Emanuel Nir, Eitan Hyam

Family Medicine Dept., Sackler Faculty of Medicine, Tel Aviv University; and Shaaraim Clinic, General Sick Fund, Rehovot; Central Cinical Laboratories, and District Medical Director, Central District of the General Sick Fund

The use of oral anticoagulant therapy (OAT) to prevent thromboembolism has been widespread in recent years. The concept of high- and low-intensity regimens has facilitated treatment for many, and has lowered the hazards of overly intense anticoagulation. However, a significant proportion of patients suited to the low intensity regimen are not being treated. It is not clear whether its wider use is limited by continued debate, lack of resources, lack of expertise, or other causes. We retrospectively reviewed the medical records of 32 patients treated with OAT administered in the primary care setting. The average age was 66±11 years (range 34-84). 9 were treated with high-intensity OAT: 8 due to artificial heart valves, and 1 due to a hypercoagulable syndrome with recurrent thromboembolism. 23 were treated with low-intensity OAT, 17 of whom had atrial fibrillation. 11 were also being treated continuously with other medication which interacted with OAT or interfered with other coagulation pathways. Such medication included: aspirin, dipyridamole, amiodarone, bezafibrate and allopurinol. Of 414 coagulation tests, 57% and 65% were in the therapeutic range in the high- and low-intensity OAT groups, respectively. There was no major bleeding event, but in 2 of 8 who bled, gastrointestinal bleeding led to hospitalization. Treatment was discontinued in 1 patient because of difficulties in achieving target INR, and in the 2 hospitalized for bleeding. The percentages of test results in, above and below the therapeutic range were similar to those in other large series, for both intensity regimens. We found that a significant proportion of patients were under chronic treatment with other medication which interacted with OAT. To estimate the rate of complications in primary care OAT, larger series are needed. We conclude that OAT can be given and monitored by the family physician, and that awareness of long and short term drug interactions with OAT is mandatory.

Liver Allografts from Donors older than 60: Benefits and Risks

Eytan Mor, Dan Shmueli, Ziv Ben-Ari, Nathan Bar-Nathan, Ezra Sharabani, Alexander Yussim, Boris Dorfman, Ran Tur-Kaspa, Zaki Shapira

Transplantation Dept. and Institute of Liver Diseases, Rabin Medical Center, Beilinson Campus; and Sackler School of Medicine, Tel Aviv University

With limited organ resources and an increasing number of candidates for liver transplantation, the world-wide trend is towards using liver allografts from donors older than 60 years. This strategy, however, may be hazardous because of the known correlation between advanced donor age and graft dysfunction. Since January 1996, each of 5 patients received a liver allograft from a donor older than 60 years. Preservation time in these cases was shortened as much as possible and liver allografts were used only if there were no other potential risk factors for primary nonfunction. Mean cold ischemic time was significantly shorter in this donor group (7.8 hrs) than for livers from 28 younger donors (10.2 hour; p<0.01). 3 of the 5 grafts from older donors had normal function immediately. The other 2 initially had biochemical features of preservation injury, but graft function returned to normal within the first week after transplantation. All 5 patients currently have normal graft function, with follow-up ranging from 3-8 months. There was no difference between the 5 recipients of grafts from older donors and 28 adult recipients of grafts from younger donors in extent of preservation injury and in immediate graft function. We conclude that in countries with limited organ resources, such as Israel, liver allografts from older donors can be used within defined limits and minimal preservation time.