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.

Diphtheria in a Highly Immunized Population 

Rivka Sheffer, Esther Marva, Rachel Mimon, Paul Slater, Avital Cohen, Tamat Shohat

Tel Aviv District Health Office, Central Laboratory and Epidemiology Dept., Public Health Services, Jerusalem

Although diphtheria vaccination is routine world-wide, outbreaks of the disease continue to occur in supposedly vaccinated populations. The incidence of diphtheria in Israel is very low, with only 3 cases reported in the past 24 years (all in unvaccinated children). In 2 of the 3 an asymptomatic carrier was identified among the patients' close contacts, presumable the source of the infection.

We describe a recent case of diphtheria. It is important for physicians to be aware of the possibility of diphtheria occurrimg despite the high rate of vaccination in our population.

Testicular Cancer: Self-Awareness and Testicular Self-Examination in Soldiers and Military Physicians

Thomas Tichler, Rony Weitzen, Aharon Feinstone, Raoul Orvieto, Marian Moskovitz, Adam Singer

Depts. of Oncology and Medicine B, Sheba Medical Center, Tel Hashomer; Medical Corps, Israel Defence Forces; Gynecology Dept., Hasharon Medical Center, Petah Tikvah; and Medical Dept. B, Fleaman Hospital, Haifa

Testicular cancer is the most common malignancy in young men. To evaluate knowledge and awareness of that cancer, and of the practice of testicular self-examination (TSE), we developed a questionnaire which was distributed to 717 male soldiers and 200 of their military physicians.

21% of the soldiers had received some explanation of the importance of TSE, but only 16% were actually instructed how to perform TSE, and only 2% practiced it regularly. 24% had never examined their testicles before, 185 only rarely, and 6% often. With increased age, TSE frequency increased, but previous education, type of military unit, and ethnic origin had no affect. 99% of military physicians had been taught how to examine breasts, but only 70% had been taught routine testicular examination. 22% performed it, but 27% never did. 84% had never taught their soldiers the importance of TSE, although 51% taught female soldiers breast self-examination.

There was a significant lack of awareness of the importance of regular practice of TSE among both soldiers and their army physicians.

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.

Physicians' Opinions about the Patient Rights Law - A Qualitative Study 

D. Steinmetz, H. Tabenkin

Dept. of Family Medicine, HaEmek Medical Center, Afula

A qualitative analysis of the question "what is your general opinion of the Patient Rights Law?" showed that most physicians think it a good law that contributes to improved relations with patients.

Physicians surveyed raised several issues relating to implementation of the law: conditions, time required to implement it and problems with language and comprehension. Fears were expressed about possible abuse of the law by patients and their lawyers, which could put medicine on the defensive.

Nevertheless, most physicians think the law positive, that it has not negatively affected their work, and contributes to improved relationships with patients. They recommend that working conditions be improved in order to fully implement the law.

The Sixth Vital Sign: End-Tidal Co² in Pediatric Trauma Patients during Transport

Amir Vardi, Inbal Levin, Gideon Paret, Zohar Barzilay

Pediatric Transport Team of the Pediatric Critical Care Unit, Sheba Medical Center, Tel Hashomer; and Sackler School of Medicine, Tel Aviv University

Transport of pediatric trauma victims, within as well as between medical centers, has become a frequent event and an integral activity of pediatric critical care units. Monitoring patients during transport is of utmost importance, as an unstable environment poses an increased threat to the patient's stability. The level of monitoring and care should approximate that of the critical care unit. Monitoring end-tidal CO² (EtCO²) has become routine for many pediatric intensive care unit patients but technical problems have limited its use during transport.

Our transport team uses a transportable EtCO² monitor of the side-stream type (NPB 75), requiring very small samples; midstream sampling overcomes humidity interference. The monitor is small and lightweight, operates on a rechargeable battery and is especially designed for the demanding environment of transport.

From October 1997 through January 1999, 187 pediatric patients, 62 of whom were trauma victims, were transported for a total of 45 hours, including 2 hours of in-flight transport. Age range was 3 months to 16 years. Of the 53 monitored for EtCO², in 9 (17%) monitoring resulted in a significant, immediate change of treatment during transport.

We find EtCO² an important adjunct in monitoring pediatric trauma patients during transport. In addition to conventional monitoring of heart rate, blood pressure, respiratory rate, body temperature and blood oxygen saturation, we suggest EtCO² as the sixth vital sign that should be monitored.

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.

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.

Noncontrast Spiral CT for Diagnosis of Acute Flank Pain

Alexander Tzivian, Igor Sherman, Yacov Yacobi,  Surin Elias, Ami Sidi, Jack Asherov

Depts. of Urology, Emergency Medicine, and of Radiology, Wolfson Medical Center, Holon

Acute flank pain is commonly encountered in the emergency department, and often requires imaging to establish its cause. For decades intravenous urography and sonography have been the primary media for evaluating flank pain.

Recently, noncontrast spiral CT (NCSCT) has been shown to be accurate and highly successful in diagnosing cause in such cases. We evaluated its use in the diagnosis of acute flank pain. During a 7-month period, 147 such cases had NCSCT imaging immediately after initial evaluation in the emergency department. Using a spiral CT scan without oral or IV contrast media, 109 of 147 cases were found to have ureteral stones, and 34 others to have other urological conditions unrelated to the cause of pain; 38 CT scans were negative for ureterolithiasis and in 14 non-urological disease was diagnosed.

NCSCT is a valuable diagnostic technique for patients in the emergency department with flank pain. It rapidly and accurately detects ureteral stones causing renal colic and also detects extra-urinary causes of acute flank pain.

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.

Specialty Clinics - Gain or Loss?

Natalya Bilenko, Luna Avnon, Fanya Shimonovich, Dov Heimer

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

We evaluated the significance of first visits to our pulmonary clinic with regard to diagnosis and treatment by reviewing records of 287 new referrals by medical care providers (Sept. 1998 - Feb. 1999). At the first visit the diagnosis was changed in 30%, and treatment in 40%. These are minimal figures because evaluation had not been completed nor the diagnosis determined in all cases, while further investigation and follow-up continued.

In light of these findings, we believe that recent pressure on primary care physicians to avoid referrals to specialty clinics would result in short-term savings, but in the long term, would increase expenses and diminish quality of care. It is important to consider ways to maximize the interaction between the primary care physician and the specialist to maintain quality of care and decreases costs.

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.