Marked Creatine-Phosphokinase Elevation in Myopathy after Treatment with Bezafibrate

G. Slobodin, D. Yeshurun

Medicine A Dept. and Hyperlipidemia Clinic, Bnai Zion Medical Center,Bruce Rappaport Faculty of Medicine and Technion-Institute of Technology, Haifa

Bezafibrate is a fibric acid derivative which has been widely used in the past 15 years. Recent studies have elucidated much of its mechanism of action, which mainly results in reduction of VLDL and triglyceride levels and in elevation of HDL. The drug is relatively safe and its side-effects well known, mild, and reversible.

The most severe side-effect is myositis, varying from mild flu-like symptoms to rhabdomyolysis, which is extremely rare. The underlying situations most frequently associated with bezafibrate-induced myositis are renal insufficiency and concomitant treatment with certain other drugs.

We describe 2 women who developed severe myositis with bezafibrate treatment. 1, aged 43, who had moderate diabetes but no renal insufficiency, was treated with metformin and warfarin, which can interact with bezafibrate and affect its metabolism. The other, aged 54, had renal insufficiency and was on home peritoneal dialysis. Her bezafibrate dose had been increased because of very high triglyceride levels.

The aim of the study is to call attention to this significant side-effect of benzafibrate and to ways of preventing it.

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.

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.

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.

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.

High-Dose Chemotherapy and Autologous Stem Cell Trans-Plantation for Refractory and Relapsing Hodgkin's Disease

A. Avigdor, I. Hardan, O. Shpilberg, P. Raanani, I. Grotto, I. Ben-Bassat

Hematology Institute and Hemato-oncology Unit, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

High dose chemotherapy and autologous stem cell transplantation are widely used in relapsed and primary refractory Hodgkin's disease. We transplanted 42 patients with Hodgkin's disease between 1990-1998. Median follow-up was 31 months (range 1-102). 29 (69%) were transplanted after relapse and 13 (31%) were refractory to first line therapy. Median age at transplantation was 29 years (range 19-58) and 23 (55%) were males.

All were treated with the BEAM protocol (carmustine, etoposide, cytarabine and melphelan). 18 who were in remission received radiotherapy following transplantation. The source of the stem cells was bone marrow in 17% and peripheral blood in 83%. At initial diagnosis: 57% had stage III-IV disease and B symptoms were present in 52%. 75% were treated with MOPP, ABVD or with related versions. Radiotherapy followed in 52%. Prior to transplantation, 45% of the relapsed group were in the advanced stage. 33% and 12% of all patients had lung and bone involvement, respectively.

The complete remission rate was 86% for the 2 groups. 2 (5%) died from transplant-related complications and MDS/AML developed in 2 (5%) after transplantation. The 3-year overall survival (OS) and disease-free survival (DFS) were 68% and 60%, respectively. The 3-year OS for the relapsed group was 64% compared with 76% for the refractory group, and the 3-year DFS for the relapsed group was 60% vs. 42% for the refractory group (neither difference significant). Radiotherapy following transplantation did not have a beneficial effect on DFS. No prognostic factors for outcome of transplantation were found, most probably due to the limited number of patients and the high variability of disease characteristics.

We conclude that high dose chemotherapy and autologous stem cell transplantation are effective and relatively safe for relapsed or primary refractory Hodgkin's disease. The DFS at 3 years was longer for those transplanted after relapse than those with primary refractory disease, but not significantly. Patients with primary refractory disease can be salvaged with high dose chemotherapy.

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.

Nutritional Status and Vitamin B⁶ Supplementation in the Institutionalized Elderly

Felicia Stern, Yitshal N. Berner, Zeev Polyak, Sophya Bernadiner, Margarita Komarnitsky, Ben Ami Sela, Ram Doolman, Yoseph Dror

Institute of Biochemistry, Food Science, and Nutrition, Hebrew University of Jerusalem; Subacute Dept. and Clinical Nutrition, Hartzfeld Geriatric Hospital, Kaplan Medical Center, Gedera; and Institute of Chemical Pathology, Sheba Medical Center, Tel Hashomer

Nutritional status and vitamin B⁶ status were assessed in 18 men and 32 women, average age 84, living in a home for the aged. Average proportion of energy derived from protein was higher than the recommended; fiber intake was very low. Also low were intakes of calcium, magnesium, zinc, copper, vitamins D and E, thiamin, folic acid and vitamin B⁶.

Supplementation with vitamin B⁶ (10mg/d) for 28 days in those with the lowest B⁶ status assessed by B⁶ intake, activation coefficient of aspartate transaminase and plasma pyridoxamine concentrations led to improved B⁶ status (marked decrease in activation coefficient) and increased synthesis and decreased degradation of many short-lived neutrophil proteins. Though our elderly enjoy a variety of foods, some have marginal deficiencies that can be improved. Therefore, in the institutionalized elderly, micronutrient supplementation should be administered at a level low enough to be safe (below recommended upper level of intake) but high enough to be effective.

Anticoagulant Treatment in Pericardial Effusion - A Therapeutic Dilemma 

Marina Katsman, Elie Shiloah, Micha Rappoport

Dept. of Medicine C, Assaf Harofeh Medical Center, Zerifin

Anticoagulant treatment for acute myocardial infarction (AMI) and pericardial effusion is controversial, since the treatment might cause hemopericardium and tamponade. On the other hand, anticoagulants are strongly indicated in many situations in AMI, including: left ventricular thrombus, unstable angina, severe heart failure, deep vein thrombophlebitis, pulmonary embolism, atrial fibrillation, as part of thrombolytic treatment, and during cardiac catheterization.

We describe a 70-year-old man who presented with both pericardial effusion and a left ventricular thrombus 3 weeks after an extensive, anterior wall AMI. Anticoagulants and corticosteroids were administered simultaneously under hem-odynamic and echocardiographic monitoring, without complications.

It is our impression that anticoagulant treatment is safe in patients with pericardial effusion.

Hospitalization for Renal Colic: Epidemiological Features and Clinical Manifestations

Yahav Oron, Amir Shahar, Eran Dolev

Sheba Medical Center, Tel Hashomer; Israel Defense Forces Medical Center; Meir General Hospital, Sapir Medical Center, Kfar Saba; and Dept. of Medicine H, Sourasky-Tel Aviv Medical Center

The medical records of all patients referred to the emergency department (ED) of Sheba Medical Center for renal colic during 1996 were analyzed. Patients discharged from the ED and those hospitalized were compared.

There was no significant difference between the 2 groups with regard to average age or sex distribution. Statistically significant differences were found with regard to frequency of chills and fever, history of renal colic, referral for renal colic during that year or hospitalization for renal colic or nephrolithiasis, previous positive imaging, stone removal by surgery or extracorporeal shock wave lithotripsy, fever exceeding 37.5^o and administration of fluids, pethidine or pramin in the ED, prolonged stay in the ED and previous appendectomy.

A conditional regression model tested the predictive value of each of those factors. Inclusion of independent variables into the model led to an overall correct classification rate of 84.43%, with 44.83% sensitivity and 93.16% specificity. There were correlations between referrals for renal colic, overall renal colic rate and average monthly temperature, so there was no pure correlation between average monthly temperature and referrals to the ED for renal colic.

The major indications for hospitalization were actually the clinical ones, indicating either an active metabolic disease or suspected obstruction of the urinary tract. Treatment in the ED and duration of the visit indicated disease severity.

Multiresistant Escherichia Coli from Elderly Patients

Ilana Slucky-Shraga, Moshe Wolk, Sofia Volis, Israel Vulikh, David Sompolinsky

Dept. of Medicine and Microbiology Laboratory, Mayanei Hayeshua Hospital, Bnei Brak; Central Laboratories, Ministry of Health, Jerusalem; and Faculty of Life Sciences, Bar Ilan University, Ramat Gan

We examined all ceftriaxone-resistant Escherichia coli isolates obtained from clinical samples during 16 months (1‚Dec. '97 - 31 Mar. '99). A total of 97 resistant isolates from 36 patients were obtained, mostly from urine specimens. Of these patients, 35/36 were over 75 years old, most lived in nursing homes, were dependent on nursing in their daily lives, and were incontinent and/or had indwelling catheters.

All 97 isolates had similar susceptibility profiles: resistant to ciprofloxacin, gentamicin, ampicillin, amoxycillin/clavulanate, tricarcillin/clavulanate, aztreonam, and cefuroxime; decreased susceptibility to ceftazidime and cefepime; and susceptible to imipenem and meropenem. Double-disc tests indicated that all strains produced extended spectrum beta-lactamase(s). All the isolates belonged to 1 of 3 E. coli serotypes: 79 were 0153:H31, 13 were 0142:H10, and 5 were 0102:H6.

Mortality in Fractures of the Hip 

Y. Titiun, Z. Eshkol, Z. Horesh, M. Soudry

Dept. of Orthopedic Surgery, Beilinson Campus, Rabin Medical Center, Petah Tikva

Prevalence of hip fractures is increasing world-wide, as the mean age of populations increases. Despite advances in anesthesia, nursing care, and surgical techniques, hip fractures remain a significant cause of morbidity and mortality in the elderly.

We operated on 65 cases of hip fractures from 1995 to the end of 1997: average age was 82.9, 72% were women, average waiting time for operation was 1.6 days, perioperative mortality was 3.5% and postoperative mortality 26.2%.

Relationship between Occupation and Clinical Characteristics during Pregnancy and Recommendation to Stop Working

S. Gazit-Nissim, E. Sheiner, M. Mazor, I. Shoham-Vardi

Depts. of Epidemiology and Health Services Evaluation, and of Obstetrics and Gynecology, Soroka University Medical Center and Ben-Gurion University of the Negev, Beer Sheba

We examined the relationship between occupation and clinical characteristics during pregnancy and medical recommendations to stop working. Using a case-control design, we compared 58 working women who had preterm births, with 126 who had delivered at term. All women were interviewed postpartum while still in hospital.

There were no differences between the groups with regard to physical activity outside the home, weekly work hours, nor duration of work. Only a small proportion had been exposed to unusually difficult working conditions, to hazardous agents or to a very uncomfortable working environment. Women who had had preterm births were advised more often to leave their jobs or modify their working patterns. Multivariate analysis revealed that the physician's decision to recommend cessation of work was influenced primarily by complications during the current pregnancy.

It appears that our patients at risk for preterm birth are probably correctly identified, and receive appropriate guidelines as to working patterns. It is possible that a poor obstetric history or previous abortions may paradoxically have a protective effect, as they influence the physician to recommend cessation of work.

Laparoscopic Ultrasound in Predicting Resectability of Choriocarcinoma

M. Shimonov, P. Schachter, G. Gvirtz, Y. Avni, A. Rosen, A. Czerniak

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

Cholangiocarcinoma accounts for about 1% of all malignant tumors. They are difficult to diagnose because of their small size and their location. Although surgical resection is the best therapeutic approach, most patients undergo unnecessary exploratory laparotomy due to incorrect preoperative diagnosis.

We present our experience with laparoscopic ultrasound (LU) in the evaluation of cholangiocarcinoma and determination of tumor spread and vascular involvement. Of 25 patients referred for surgery, 6 were excluded following LU and were referred instead for palliative treatment. Diagnosis of the tumor was successful in 92%, and vascular involvement was diagnosed in 46%. LU should be an integral diagnostic test in the evaluation of choriocarcinoma.

What Primary Care Physicians Think of Israel's Health Policy Reform

Revital Gross, Hava Tabenkin, Shuli Brammli-Greenberg

JDC Brookdale Institute, Jerusalem, HaEmek Hospital, Afula; and Ben-Gurion University of the Negev, Beer Sheba

Opinions of the National Health Insurance (NHI) Law held by primary care physicians were surveyed. A questionnaire was submitted (April-July 1997) to 930 primary care physicians employed by sick funds, including general practitioners, family physicians, pediatricians and internists. Response rate was 86%.

They supported the main components of the NHI law. It was considered desirable "to a great" or "very great extent" to allocate funds to sick funds based on age and number of members (76%), to require them to accept all applicants (72%), to designate a uniform basket of services (65%), to allow members to transfer freely between funds (63%), and to allow sick funds to sell supplemental insurance (59%). However, only 41% were satisfied with the implementation of the law.

Multivariate analysis showed that employment by Maccabi, Meuhedet, or Leumit sick funds had an independent effect on low satisfaction with the law as implemented, and on negative opinions about the uniform basket of services, the accepting of all applicants, and allocation of funding based on age and number of members. Those employed by the Maccabi and Meuhedet funds were in favor of allowing sick funds to sell supplemental insurance.

The findings of the study have implications for policy-makers interested in increasing support for national health reform by physicians. It is important to examine possibilities of developing direct channels of communication between national policy-makers and physicians, as well as institutionalizing mechanisms that involve physicians directly in formulation of national policy.