Acute Lymphoblastic Leukemia in Adults Treated with German Multicenter Study Group Protocols

G. Goldstein, O. Shpilberg, P. Raanani, A. Chetrit, I. Ben-Bassat

Institutes of Hematology and of Clinical Epidemiology, Sheba Medical Center and Sackler Faculty of Medicine, Tel Aviv University

Acute lymphoblastic leukemia (ALL) is a malignant disease whose incidence is relatively low among adults, unlike in children. Adults with ALL have a lower rate of long-term disease-free survival. During the last 20 years, a German multicenter group has shown that their protocol have achieved good results in adult ALL.

We reviewed the medical records of 35 ALL patients, aged 19-63 years, whome we treated with these protocol (1988-1997). The remission rate was 94%. At a median follow-up of 46 months the 2-year overall survival was 54% and the disease-free survival was 94%. Although 2 patients died of bone marrow transplant complications, no death was directly associated with drug toxicity. The main grade 3 or 4 side effects (WHO classification) were neutropenia (91%), thrombocytopenia (71%) and anemia (71%).

With there protocols we achieved high overall and disease-free survival rates, especially in comparison with other reports. Despite the high rate of severe treatment toxicity, there were no fatalities directly related to treatment. These results emphasize the need to concentrate treatment of adult ALL patients in large medical centers with expertise in the use of the complicated treatment protocols required.

ח' טבנקין¹, ד' שטיינמץ², פ' חמאייסי¹, ע' תמיר²

¹המח' לרפואת המשפחה, מרכז רפואי העמק ומחוז הצפון, קופ"ח כללית, שלוחת הצפון של המכון להתמחות החטיבה לבריאות הקהילה, הפקולטה למדעי הבריאות בנגב. ²המח' לאפידמיולוגיה ולבריאות בקהילה, ביה"ח כרמל, הפקולטה לרפואה, הטכניון – חיפה.

Mitral Valve Repair in Ischemic Cardiomyopathy with Severeleft Ventricular Dysfunction

Dani Bitran, Ofer Merin, Jeffrey Fisher, Nadiv Shapira, Marc W. Klutstein, Shuli Silberman

Depts. of Cardiothoracic Surgery, Anesthesiology and Cardiology, Shaare Zedek Medical Center, Jerusalem

Patients with ischemic mitral insufficiency and poor left ventricular function are high operative risks. We present 101 patients who had mitral valve repair in our department: 21 had severely reduced left ventricular function, 19 were in NYHA functional Class IV, and 2 in Class III. All had concomitant coronary artery bypass.

There was no early operative mortality, but there were 2 late deaths (9.6%). At follow-up (3-36 months) all valves were functioning normally, 9 patients (43%) were in NYHA functional Class I, and 4 (19%) in Class II.

Our experience shows that repair of ischemic mitral insufficiency in the presence of severe left ventricular dysfunction can be performed with good results, and is preferable to mitral valve replacement. Late follow-up showed significant symptomatic improvement.

Man in a Hot Climate - Early Studies of the Institute of Military Physiology 

Ezra Sohar, Yair Shapiro, Yoram Epstein

Institute of Military Medicine, Medical Corps, Israel Defense Forces and Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer

In the 1950's many IDF soldiers were hospitalized for heat stroke - about 25% of whom died. Analyzing these cases revealed that commanders misinterpreted human ability to perform in the heat and ignored basic concepts of fluid and electrolyte balance and heat load.

In the early 1960's a series of studies was conducted with regard to soldiers' performance in the heat. The first study (1959), which later became a classic, was conducted during a 21-day march from Eilat to Metula, crossing all climatic zones of Israel. The study was followed by other investigations which approached the issues of voluntary dehydration, fluid consumption vs sweat loss, salt additives, and the effect of heat load on performance.

Based on these early studies, proper regulations were issued to field officers. Over the years, the lessons learned from these studies saved many lives. The number of cases of heat stroke and of other climate-related injuries was dramatically reduced, and performance was enhanced.

Prediction of Physiological Response from Mathematical Models 

Yoram Epstein, Yuval Heled, Daniel Moran, Yair Shapiro

Institute of Military Medicine, Medical Corps, Israel Defense Forces and Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer

The ability to predict the physiological responses of workers exposed to extreme environmental conditions, has been a challenge to environmental physiologists for more than 3 decades. Therefore, mathematical models have been developed to predict metabolic rate under various levels of work intensity and dynamic changes in body temperature and heart rate.

Based on the effect of exercise on the cardiovascular system, a model was developed to predict mean arterial blood pressure as a function of heart rate. Physiological strain could also be estimated on the basis of thermoregulatory and cardiovascular strains.

This paper summarizes knowledge accumulated during 25 years of studies in the field of mathematical modeling of physiological parameters. Besides analyzing the logic underlying each model, it explains the scientific approach in developing a model from its early concept to the model's application in the field.

Infectious Mononucleosis in Adults - A Diagnostic Challenge

G. Goltzman, S. Nagornov, M. Horwitz, M.J. Rapoport

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

The adult form of mononucleosis caused by Ebstein-Barr virus (EBV) is different from the disease in children and adolescents. In most adults there is no pharyngitis or lymphadenopathy, fever is much more prolonged, abnormal liver function is frequent and lymphocytosis and the presence of atypical lymphocytes are not common. Such an atypical disease presentation often results in delayed diagnosis and unnecessary treatments. We describe 2 adults with such atypical presentations and complications of EBV infection.

Placenta Accreta with Placenta Previa after Previouscesarean Sections 

Eylon Lachman, Alexander Mali, Gabriel Gino, Michael Burstein, Michael Stark

Depts. of Obstetrics and Gynecology and of Pathology, Misgav Ladach Hospital, Jerusalem

The increased rate of cesarean sections in recent decades has brought with it an increase in the frequency of placenta accreta. There are direct correlations between previous cesarean deliveries and also maternal age, with the risk of placenta accreta. There is also a direct correlation between placenta accreta and placenta previa.

The risk of placenta accreta in women who have had placenta previa is 2% for those younger than 35 years and with no history of uterine surgery. The risk increases to 39% for those over 35 who have had 2 or more cesarean sections.

We present 3 cases of placenta accreta admitted in 15 months, all of whom had a history of cesarean sections. The frequency of placenta accreta in our hospital is 1:1,579 deliveries, in line with the 1:1,420 in the literature. We consider hysterectomy the treatment of choice for this serious complication. When performing a cesarean in cases of placenta previa with a history of cesarean sections, the possibility of placenta accreta should be considered.

Carbamazepine Hypersensitivity 

Shimon Ivry, Doobi Shteinmintz, Hava Tabenkin

Dept. of Family Medicine, HaEmek Hospital, Afula and National Residency Institute, Ben-Gurion University of the Negev, Beer Sheba

Carbamazepine (C) can cause a characteristic hypersensitivity reaction (CHS}. This multisystem reaction typically presents as fever, mucocutaneous eruption and lymphadenopathy. The syndrome usually develops between 1 week and 3 months after starting therapy, with involvement of the liver, lung, kidney and inappropriate secretion of ADH. The incidence is less than 0.001% in those treated with C and it is diagnosed clinically. With onset of CHS, the drug must be stopped and if there is no improvement, cortico-steroids should be started. When the diagnosis is in doubt, the patch test, lymphocyte transformation test, macrophage migration inhibitor factor, and other tests can be helpful.

The pathogenesis is not known. Similar syndromes have been described with phenytoin and phenobarbital. There is clinical and in-vitro evidence of cross reactions between C and phenytoin. It is not known whether the CHS syndrome should be considered a premalignant state, with increased risk for the development of malignant lymphoma.

Transient Ischemic ECG Changes in Acute Cholecystitis without History of Ischemic Heart Disease

Lior Lowenstein, Amer Hussein

Dept. of Emergency Medicine, Bnai Zion Medical Center, Bruce Rapport Faculty of Medicine, Haifa

That abdominal distention, nausea, and chest pain may be accompanied by ischemic ECG changes is well known and has been described in the literature. However, very few cases have been reported with acute cholecystitis and ECG changes not due to cardiac ischemia.

We present a previously healthy 20-year-old woman admitted with acute cholecystitis. Prior to surgery routine ECG showed ST-depression and T-wave inversion. The day following cholecystectomy the ECG returned to normal. 1 month later, ergometry and echocardiography were both negative.

Based on the literature and our personal experience, although ECG changes may occur in acute cholecystitis, the possibility of cardiac ischemia must be excluded. However, when no cardiac basis is found, ultrasound of the biliary system might reveal the cause of these ECG changes. Thus, in acute cholecystitis with ischemic ECG changes but no other laboratory or clinical evidence of cardiac ischemia, ECG changes alone are not a contraindication to cholecystectomy. Furthermore, delay in treatment could be harmful.

Management of Compound High Energy Injuries of the Limbs 

A. Lerner, I. Weisz, G. Nierenberg, D. Horer, H. Stein

Dept. of Orthopedic Surgery A, Rambam Medical Center, and Technion Medical Faculty, Haifa

We treated 49 patients with high energy injuries of the limbs between 1.1.94-31.12.97. They had sustained 61 fractures, 50 of which were open; 14 had bilateral injuries, and 3 had lost a limb. All fractures were stabilized on arrival with an A-O tubular external fixator. Soft tissue loss was covered by a combination of split skin graft and tissue flaps following repeated surgical debridement.

After 10 days, or when all soft tissue defects were covered, the cantilever external fixation frame was exchanged for a hybrid ring which provided three-dimensional stability and allowed early full weight bearing and joint mobilization. The hybrid ring frame did not interfere with the care of soft tissue injuries. Furthermore, it kept the risk of developing deep infections to a bare minimum. At follow-up after a median of 20 months, 1 patient had developed osteomyelitis but all had returned to independent function.

Botulin Toxin for Spasticity in Spinal Cord Damage

Ofer Keren, Flabia Shinberg, Amiram Catz, Neer Giladi

Loewenstein Rehabilitation Hospital, Ra'anana; Movement Disorder Unit, Tel Aviv Medical Center; and Sackler Faculty of Medicine, Tel Aviv University

Therapeutic injection of botulin toxin is well-recognized for reducing tonus in local dystonia. However, its efficacy in reducing spasticity in spinal cord injuries is still unproven. 4 men and 1 woman (mean age 39 years, range 20-56) with spinal cord injury and debilitating spasticity, and no response to standard treatment for spasticity received injections of botulin, 200-300 U, into 4-8 points in their legs to block muscle-nerve synapses.

In all 5 tonus was reduced in the area of the block, while in some it was also reduced in more distal muscles. In 1 there was reduced tonus in both the injected and contralateral leg. The therapeutic effect on tonus persisted for 3 months. In spite of objective improvement in tonus in all 5, only 3 felt subjective improvement, but in none was there improvement on standard functional scaling.

We found injection of botulin toxin effective in reducing tonus in the spinal cord-injured, and to some extent in improving subjective feeling of well-being in some of them. Obective measurement might show functional improvement after larger doses of toxin injected into more muscles. This might be necessary because the muscle mass of the legs is large and the intensity of involuntary contraction is especially high in these patients.

Does Incidence of Hepatitis AIncrease During Shmitah (The Sabbatical Year)?

Zvi Ackerman, Ita Goldstein, Elizabeth Ackerman

Depts. of Medicine, Hadassah University Hospital, Mount Scopus; Bikur Holim Hospital; Hebrew University-Hadassah Medical School; and Pediatrics Dept., Kupat Holim, Jerusalem

In Israel the biblical injunction of the sabbatical year (shmitah) prevails, whereby all Jewish-owned land should lie fallow during every seventh year. Consequently, it is customary for members of the orthodox Jewish community to eat only produce grown by non-Jews (Arabs). Many Arab farmers use sewage water for irrigation and since such water could be infected with hepatitis A virus (HAV), there is concern about the possibility of HAV epidemics during the sabbatical year.

We therefore we examined the data of the Israeli Center for Disease Control (ICDC). We found no obvious increase in incidence of viral hepatitis during, nor in the year immediately after, all sabbatical years since 1951. However, the data was not comprehensive as it included only partial information on morbidity from HAV in our Jewish inhabitants. Also, there was no data specific for the orthodox Jewish community, which is especially at risk for HAV from sewage-irrigated vegetables. Irrespective of shmitah, there should be constant effort to prevent HAV infection in Israel.

Physiological Aspects of Women in Combat

D. Libster, Y. Heled, Y. Shapiro, Y. Epstein

IDF Institute of Military Physiology and Heller Institute for Medical Research, Sheba Medical Center, Tel Hashomer

Since military service is physically demanding, soldiers must maintain high levels of physical fitness for optimal performance of their duties. Women are at a physiological disadvantage when competing against men: they have a smaller muscle mass, more body fat, lower red blood cell counts, lower hemoglobin levels and smaller cardiac outputs. Women are slower and weaker than men and more prone to exercise-induced skeletal injuries. Fewer women than men meet the standards of physically demanding jobs. Therefore integrating women into physically demanding military-oriented jobs requires redesigning or modifying the tasks (different pace, mechanical aids, teamwork). While physical training can increase the physical capacity of women, training cannot completely eliminate gender differences. Thus the data presented do not imply that women cannot be integrated into combat units, but highlight gender-related differences which might have an effect on the ability of women to compete equally with men at the same task.

Follicular Splenic Lymphoid Hyperplasia Associated with EBV Infection

Boleslaw Knobel, Enrique Melamud, Sharon Nofech-Moses, Liliana Zeidel

Dept. of Medicine B and Institute of Pathology, Edith Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel Aviv University

Massive splenomegaly is defined as a spleen weighing about 10 times normal weight. We describe a 36-year-old man who had huge splenomegaly and secondary pancytopenia simulating malignant lymphoma for about 3 months. Splenectomy was necessary because of the suspicion of hematologic malignancy, especially isolated lymphoma of the spleen, and pain and mechanical abdominal disturbances.

On operation, the spleen was 25 cm long and weighed 250 g. There was florid, reactive follicular lymphoid hyperplasia. Immunohistochemical staining with CD-20(L26), CD-45Ro(UCHL), bcl-2 oncoprotein (Dakopatts), EBV (anti-EBV mol weight 60 KD, Dakopatts) was consistent with reaction to EBV infection and not with follicular lymphoma. Lack of PCR amplification using DNA extracted from paraffin-embedded splenic tissue indicated absence of a monoclonal B cell population carrying rearranged immunoglobulin genes. The lymphocytic population was proven polyclonal by the negative results of PCR for the bcl-2 gene rearrangement. EBV seroconversion from high titer antibodies of anti-EBV-VCA-IgM to negative, and from negative EBNA to positive was consistent with an apparent primary EBV infection.

We have not found on computerized search a previous report of reactive follicular splenic hyperplasia to EBV infection causing huge splenomegaly, with or without EBV-induced infectious mononucleosis.

Can Police Car Flashing-Light Induce Encephalographic Discharges and Seizures?

G. Vainstein, V. Yofe, N. Gadoth

Dept. of Neurology, Meir General Hospital, Sapir Medical Center, Kfar Saba

The new police car flashing-light device (930 Heliobe Lightbar) has recently been implicated as potentially epileptogenic. We exposed 30 epileptic patients, 30 nonepileptic patients who suffered from headache and 15 normal volunteers to this light source. All had routine EEGs with standard intermittent photic stimulation, followed by 3-minute stimulation with the Lightbar. In none were either seizures or EEG changes induced. In 1 epileptic spike-and-wave activity induced by standard photic stimulation was enhanced with the Lightbar.

We could not confirm that the Lightbar is epileptogenic.