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.

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.

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.

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.

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.

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.

Treatment of Sputum Retention by Minitracheostomy 

A. Ben-Nun, E. Altman, L.A. Best

General Thoracic Surgery Dept., Rambam Medical Center, Haifa

Maintenance of bronchopulmonary hygiene is mandatory for preventing complications of respiratory therapy in the hospitalized patient. Removal of secretions from the tracheobronchial tree is crucial. Conventional therapy, designed to assist in dislodging airway secretions, includes chest physical therapy, incentive spirometry, transnasal endotracheal suctioning and bronchoscopy.

Minitracheostomy was first described by Matthews and Hopkinson for recurrent endotracheal suctioning in 1984. Since then there have been few papers about it, but they report good results with low morbidity. Despite this, its use is not popular in routine clinical work.

We report our experience with minitracheostomy in the prevention of sputum retention. We conclude that its use is easy, safe and very effective in preventing postoperative and post-traumatic respiratory complications.

Breaking Bad News - A Structured Course for Primary Care Physicians 

Lea Ungar, Mordechai Alperin, Gilad Amiel, Zvi Behrier, Shmuel Reiss

Family Medicine Dept., Kupat Holim Klalit Health Services, Western Galilee District; Medical Education Unit, Bruce Rappaport Faculty of Medicine, Technion Institute of Technology; and Urology, Dept., Bnei-Zion Medical Center, Haifa

Physicians are frequently required to break bad news to their patients. Previous research has shown that inconvenience, incompetence, and difficulty in dealing with patients' feelings are the main complaints expressed by physicians after such an encounter. Current educational programs dealing with breaking bad news are usually short, given in lecture format, and are inadequate in addressing essential issues such as knowledge, personal beliefs and attitudes, and previous personal experiences of physicians in such situations.

In the past 8 years our Dept. of Family Medicine has implemented a course in breaking bad news that addresses these issues. A senior family practitioner and a medical social worker conduct 14 sessions of discussions and role-playing for small groups of residents and primary care physicians. The program is based on: theory dealing with methods of managing stress and crisis intervention, clarifying personal attitudes, discussions of previous personal encounters of the participants, various modalities of communication, methods of addressing patients' feelings and emotions, and coping with the emotions of the one breaking the bad news.

On a 1-5 Likert scale questionnaire the course received an overall score of 4.47 (SD 0.51). Participants noted that they gained relevant communication skills for future patient encounters. A reliable examination of practitioners' competence in breaking bad news is mandatory in order to assess the efficiency of such courses.

Systemic Mastocytosis

K. Sade, I. Dotan, Y. Levo

Depts. of Pulmonary and Allergy Diseases and of Medicine T, Tel Aviv-Sourasky Medical Center

Mastocytosis has a highly variable clinical expression, and systemic mastocytosis is occasionally associated with a myeloproliferative or a myelodysplastic disorder. These patients often present without skin involvement and have a very poor prognosis. We report a 72-year-old man with this condition who had spells of flushing and dyspnea, myelo-fibrosis, and high serum and urine histamine levels.

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.

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.

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.

Gastrointestinal Hemorrhage of Obscure Origin

Yoel Siegel, David Ergaz, Oscar Liphshitz, Felix Gottesfeld, Zev Sthoeger

Depts. of Medicine B and Surgery, and Gastroenterology Unit, Kaplan Medical Center, Rehovot (Associated with Hebrew University-Hadassah Medical School, Jerusalem)

Gastrointestinal bleeding of obscure origin consists of recurrent bouts of acute or chronic bleeding for which no definite source is discovered in routine endoscopic and barium contrast studies of the upper and lower gastrointestinal tracts. Usually its cause is angiodysplasia of the intestine, but many cases are due to tumors, mostly of the small bowel, which may be malignant.

In patients under the age of 50, the proportion with malignancy is relatively high (up to 14%) as compared to older patients. We describe a 45-year-old woman who suffered from gastrointestinal bleeding for 3 years. The cause of bleeding was not found despite extensive work-up.

In her last admission for acute gastrointestinal hemorrhage she was given a total of 30 units of blood. A tumor of the small intestine found by angiography was excised and found to be a stromal tumor of uncertain malignant potential. 1 year after operation she is asymptomatic without bleeding and her hemoglobin is stable without treatment.

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.

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.