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.

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.

Trends in Epidemiology of Hepatitis in the Israel Defense Forces 

Michael Gdalevich, David Gillis, Daniel Mimouni, Itamar Grotto, Ofer Shpilberg

Institute of Military Medicine, Medical Corps, Israel Defense Forces

During the 50's and 60's there were large scale epidemics of hepatitis A every 3-4 years in the Israel Defense Forces. During these epidemics the annual incidence exceeded 10/1000 soldiers at risk. There has been a highly significant decrease in rates during the past 30 years. The average annual incidence of clinically identified viral hepatitis A decreased from an average of 6/1000 during the 60's to 2.5/1000 during the 70's. The decrease coincided with the introduction in the 1970's of wide-scale post-exposure prophylaxis with immune serum globulin (ISG). The incidence was further significantly reduced to 0.5-1.0/1000 with the introduction of pre-exposure prophylaxis with ISG, starting in 1978 (p<0.001).

Other factors probably played a role in accelerating the decline in morbidity, such as improvement in personal hygiene and sanitation facilities, and in waste disposal and other aspects of military environmental health.

These improvements were probably more pronounced in the civilian sector, leading to decreased exposure of children to the virus and consequently a higher proportion of seronegatives at induction. Increase in the proportion of recruits without natural immunity to the virus poses greater risk, both in terms of personal morbidity as well as military operational ability. This risk, combined with problems of ISG use and availability, has propelled hepatitis A prevention policy towards the use of the new inactivated vaccines.

Tracheoesophageal Puncture after Total Laryngectomy

Roy Landsberg, Frida Korenbrot, Dov Ophir

Depts. of Otolaryngology and of Head and Neck Surgery, Meir Hospital, Kfar Saba and Sackler Faculty of Medicine, Tel Aviv University; and the Israel Cancer Association Voice Rehabilitation Program

Total laryngectomy due to malignant laryngeal tumors is followed by loss of speaking ability. Voice restoration in laryngectomized patients is the main target in their rehabilitation. Until the late 70's, esophageal speech was considered the most effective rehabilitation method. In 1980 Singer and Blom introduced a prosthesis for tracheoesophageal speech which has been gaining popularity. Tracheoesophageal puncture (TEP) can be performed either at the time of total laryngectomy, or later.

30 of our patients underwent TEP between 1991 and 1999, 15 at the time of total laryngectomy and 15 as a delayed secondary procedure. Mean follow-up was 36 months (range 6 months to 8 years) during which all regained speaking ability.

Over the long range, speech rehabilitation with the prosthesis was successful in 24 (80%). In only 1 in the primary TEP group did treatment fail, as the prosthesis had to be removed due to local recurrence of the tumor. Long range failure in 5/15 patients after secondary TEP stemmed from difficulties some patients had in handling the prosthesis and from psychological difficulties in adapting to the new speech device. Complications were mostly minor and occurred mainly in the secondary TEP group.

TEP performed at the time of total laryngectomy, or later as a secondary procedure, is effective for speech rehabilitation after laryngectomy.

Identifying the Elderly at Risk for Falling 

D. Galinsky, V. Fried, A. Biderman, J. Cwikel, Y. Ben Moshe

Geriatric Dept., Soroka University Hospital and Depts. of Family Medicine and of Social Work, Faculty of Health Sciences, Ben-Gurion University of the Negev; and ESHEL, Beer Sheba

Falling is one of the main problems affecting the health of the elderly. A community project was carried out to detect elderly people at high risk for falls. One of its aims was also to develop tools allowing primary care professionals to detect the elderly at risk for falling. Such a screening test in the community-dwelling elderly (EFST) and a protocol for diagnosis and treatment of the elderly at risk for falls is presented.

Breast Conservation: Safe for Early Breast Cancer

Gil Bar-Sella, Georgetta Fried, Zipora Brotman, Anna Ravkin, Riva Borovik, Abraham Kuten

Dept. of Oncology, Rambam Medical Center; Dept. of Oncology, Lin Medical Center; and Rappaport Faculty of Medicine, Technion, Haifa

Between 1981-1993 581 women with primary breast cancer were treated by breast conservation. Their mean age was 56‏12 years and 63% were postmenopausal and 37% pre- or perimenopausal. The median follow-up time was 56 months. 45% had pathological Stage I disease, 49% Stage II, 2.5% Stage III and 3.5% clinical Stage I-II disease. 54% of lesions were excised with good margins, 10% with close margins (<0.5 cm), 9% with microscopic residual, 3% with macroscopic residual, and in 24% margins were not reported. Adjuvant therapy, consisting of combination chemotherapy and/or hormones, was given to 69%.

Radiotherapy, usually 50 Gy tangential photon irradiation to the whole breast, was given to 564 (97%); an electron or photon "boost" to the tumor with a median dose of 17.5 Gy was given to 378 (65%). Most of those with positive nodes received 50 Gy to the lymphatic drainage system.

1 year after radiotherapy cosmetic results were rated as "good" or "excellent" in 80%, "moderate" in 17% and "poor" in 3%. The 5-year actuarial survival was 97% in Stage I and 88% in Stage II. 37 patients (6.5%) developed breast recurrence; 11 of these (2%) had simultaneous distant metastases. 5 (<1%) developed axillary or supraclavicular lymph node metastases, and 81 (14%) developed distant metastases. Most local recurrences were in those younger than 40, and in those with primary tumors >1.75 cm.

The satisfactory level of local control achieved is attributed to the high doses of radiation (up to 75 Gy) administered to those with high risk lesions.

Propafenone Dose for Emergency Room Conversion of Paroxysmal Atrial Fibrillation

D. Antonelli, A. Darawsha, S. Rimbrot, N.A. Freedberg, T. Rosenfeld

Dept. of Cardiology and Emergency Room, Central Emek Hospital, Afula

Paroxysmal atrial fibrillation (AF), a frequent cause of repeated hospitalization, is effectively treated with propafenone. The time to conversion to sinus rhythm is a consideration when managing AF in the emergency room. We investigated the conversion rates of paroxysmal AF by 3 different oral propafenone (P) regimens, in terms of time to conversion.

188 patients with onset of AF within 48 hours were treated with propafenone (P): 48 received 600 mg as a first oral dose followed after 8 hrs by 150 mg (Group A); 82 received 300 mg as a first dose, followed by the same dose 3 and again 8 hrs later (B); 58 received 150 mg every 3 hrs, up to a total dose of 600 mg (C). P was stopped when sinus rhythm was achieved.

Rates of conversion to sinus rhythm after 3 hrs in the 3 groups were: 46%, 41% and 26% respectively; after 8 hrs: 77%, 78% and 70%; and after 12 hrs: 81%, 84% and 76%. Treatment was discontinued in 8. There was excessive QRS widening (>25% of the basal value) in 1 in group A, 1 in group B and 2 in group C; wide-QRS tachycardia occurred in 4 in group B. In Group A there was a higher rate of early successful conversion, with a lower incidence of side-effects than with the other regimens.

Use of Abciximab (Reopro) in the Catheterization Laboratory and in Unstable Coronary Syndromes

Shmuel Banai, Andre Keren, Nataly Daniel, Jesaia Benhorin

Heiden Dept. of Cardiology, Bikur Cholim Hospital, Jerusalem

Blockage of platelet glycoprotein IIb/IIIa receptor by Reopro c7E3 Fab-abciximab) has been shown to reduce markedly ischemic complications during and following elective and high-risk coronary intervention CI). Between July ’96 and February ’98, 120 consecutive patients (85 men and 34 women, aged 34-90 - mean 62) received Reopro (20 mg bolus, followed by 10 mg/min for 12-48 hours). 100 were treated with Reopro in the catheterization laboratory, in 76 as prophylactic treatment preceding high-risk CI and in 24 as bailout treatment for acute complications during CI. 20 additional patients were treated in the CCU for acute coronary syndromes, 17 of whom underwent CI 6-48 hours later.

Coronary angiography demonstrated multivessel disease in 66 (56%), and the target lesions were LAD - 77, RCA - 41, LCX - 22, SVG - 6, and 2 unprotected LMCA (total: 148 lesions dilated in 117 patients). Of the 117 CI, 44 were PTCA alone, and 73 included stenting.

Indications for prophylactic Reopro for high risk CI were: acute MI (48 hours), early post-MI angina, unstable AP, and/or complex anatomy with visible thrombus. In this high-risk population the overall success rate (open artery, no MI, discharged alive, no need for urgent re-vascularization) was 97% when Reopro was given prophylactically prior to CI. The success rate was lower (87.5%) when Reopro was given in bailout situations.

In 20 patients with acute coronary syndromes treated in the CCU while receiving maximal combined conventional therapy (including full-dose heparin), all symptoms and dynamic ischemic ECG changes disappeared within minutes following Reopro. 17 underwent successful CI during hospitalization and 3 were treated medically.

Reopro given prior to high risk CI was associated with a very low rate of complications. In a few cases with acute coronary syndromes, Reopro given in the CCU cases immediate relief of myocardial ischemia and reduced the need for urgent coronary intervention.

Comparison between Every-Day and Every-3-Days Fluoxetine in Young, Moderately Depressed Out-Patients

A. Shiber, H. Reuveni, A. Elhayany, I.Z. Ben-Zion

Psychiatric Dept., Psychiatric Division, Soroka Medical Center and Ben-Gurion University of the Negev, Beer Sheba; and Medical Division for Drug Utilization, Kupat Holim Klalit (Sick Fund)

Fluoxetine is now a well-known and often-used specific serotonin reuptake inhibitor (SSRI) and antidepressant. It has a very long active half- life, from 2-16 days. Our hypothesis was that sufficient therapeutic effectiveness would be achieved by prescribing the drug less frequently than once a day.

To establish whether there is a difference between fluoxetine given daily or every 3 days, we assigned 25 outpatients with mild to moderate, acute major depressions (DSM-IV) to receive fluoxetine (20 mg), either each day or every 3 days. The study was open-labelled, using for assessment the HAM-D, GHQ-28 side-effect checklist and clinical judgment questionnaires. Follow-up lasted 6 months.

Results indicated no differences in the clinical outcomes, except for slightly fewer side-effects in the study group. Although the open label design limits drawing definitive conclusions, our preliminary results provide more information, and support our hypothesis that low-dosage fluoxetine is beneficial. However, more comprehensive, double-blind studies are necessary to confirm our preliminary results.

Serotonin Re-Uptake Inhibitors as Primary Therapy for Carotid Sinus Hypersensitivity

Amos Katz, Angel Kantor, Alexander Battler

Cardiology Dept., Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Carotid sinus syndrome is a well-recognized cause of unexplained syncope in older patients, and may lead to significant morbidity due to trauma from falls. Dual chamber pacing has been shown to be effective in relieving symptoms due to bradycardia, but not due to vasodepressor response. We report an 84-year-old man with recurrent syncope due to carotid sinus hypersensitivity. He was treated only with a serotonin re-uptake inhibitor and was symptom-free after 3 weeks of therapy. He has remained symptom-free for the past year.

Nonpenetrating Deep Sclerectomy

Orna Geyer

Ophthalmology Dept., Tel Aviv-Sourasky Medical Center

This is the first report from Israel of nonpenetrating deep sclerectomy (DS), a new operation for the surgical management of glaucoma. It facilitates ocular fluid drainage without entering the eye. It involves performance of a conjunctival flap and creation of a 565 mm superficial scleral flap. A deeper scleral flap is dissected off the scleral bed together with the roof of the canal and corneal stroma, leaving behind the wall of the canal and membrane. Aqueous will flood the dissected area. A collagen device is then sutured to the scleral bed, the superficial scleral flap sutured into position and the conjunctiva closed. With this procedure, the surgeon can avoid the common complications of conventional glaucoma surgery.

We report a 6-month follow-up of 15 patients after DS. Mean preoperative intraocular pressure was 26.7+2.5 mm Hg, which decreased to 15.5+4.7. After 6 months there was no change in visual acuity after surgery. DS is associated with good middle-term intraocular pressure control and a low rate of postoperative complications. It is therefore a good alternative to standard glaucoma surgery.

Rupture of Pectoralis Major Muscle: Operative Treatment of an Uncommon Sport Injury

Moshe Weisbort, Gad J. Velan, David Hendel

Orthopedics Dept., Rabin Medical Center (Golda Campus), Petah Tikva

Rupture of the pectoralis major muscle in an athlete is rare, but is said to be common in weight lifters. The muscle usually ruptures at the musculotendinous junction during forceful contraction of the muscle in adduction, forward flexion and internal rotation of the arm. We describe an athlete who suffered such a major tear during a rugby game. It was treated surgically and after adequate rehabilitation, athletic activities were resumed.

Evaluation of a Local Infant Formula Enriched with Polyunsaturated Fatty Acids

Zvi Weizman, Elena Brutman, Drora Leader, Chaim Zegerman

Pediatric Gastroenterology Dept. and Nutrition Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center, Beer Sheba;

and Ma'abarot Products Industry, Kibbutz Ma'abarot

Polyunsaturated fatty acids (PUFA) are vital for the normal development of the brain and the eye retina in infancy. Breast milk contains significant amounts of PUFA, and compensates for their low production in infancy. Only recently a few companies with worldwide product distribution have started to enrich infant formula with PUFA. We evaluated the safety and clinical efficacy of a locally made PUFA-enriched infant formula, produced for the first time in Israel.

50 normal, full term infants participated in a prospective, randomized double-blind study. Half received a regular whey-predominant infant formula (Materna Plus), and the other half a PUFA-enriched formula (Materna Premium), both produced in Israel, for 30 days. Evaluation included physical examination, growth parameters, stool analysis, daily parental questionnaires regarding infant behavior and defecation, and developmental assessment.

There were no significant differences on comparing growth parameters, infant behavior, attacks of restlessness, gas severity, or stool characteristics in the 2 groups. There were no side effects or abnormal stool findings in either group, and no differences in developmental assessment at 3 months of age.

We conclude that the locally-produced PUFA-enriched infant formula is safe and clinically efficient. We assume that the lack of any effect on developmental indices is due to the relatively short exposure to the PUFA-enriched diet. Nevertheless, based on the recent literature, there is no doubt that PUFA supplementation isvital in improving infant brain and eye development.

Chemical Synovectomy in Arthritis by Intra-Articular Injection of Osmic Acid

D. Markovits, M. Rozenbaum, I. Rosner, E. Rottenstriech

Dept. of Medicine A, Carmel Hospital; Rheumatology Unit, Bnai Zion Hospital; and Zevulun Medical Clinic, Haifa

18 patients suffering from persistent synovitis despite medical therapy were treated with an intra-articular injection of osmic acid. After 1 year of follow-up, 68% had good results and there were no complications nor detectable radiographic evidence of disease progression. Because osmic acid is almost as effective as surgical synovectomy and is cheap and easy to administer, it can be recommended as the first choice for treatment of corticosteroid-resistant arthritis in the early stages of the disease.

Pelvic Lytic Lesion and Osteoporosis-Related Fractures

Yaron Weisel, Ehud Rath, Nissim Ohana, Dan Atar

Orthopedic Dept., Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Insufficiency fractures of the pelvis may be overlooked as a cause of hip or groin pain. These fractures occur in the elderly, usually those with pronounced osteopenia of the pelvis. Predisposing factors include corticosteroids, local irradiation and postmenopausal osteoporosis. These fractures are difficult to detect clinically and plain radiographs and other studies may be misleading, delaying diagnosis and treatment. A 65-year-old woman had left groin and hip pain for 2 months with no history of trauma. Plain radiographs showed lytic lesions in the left pubic rami. Bone scan revealed increased uptake in that region, suggesting metastatic bone disease. Computed tomography and magnetic resonance imaging demonstrated fractures in the left superior and inferior pubic rami, with callus formation with no involvement of soft tissues. Quantitative computed tomography indicated low calcium concentration, below fracture threshold. The diagnosis of insufficiency fractures of the pelvis was confirmed by the favorable clinical and radiographic outcome. It is therefore important to be familiar with the appearance and location of these fractures.