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.

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.

Use of Civilian Emergency Departments by Israel Defense Force Soldiers 

A.D. Cohen, A. Porath, R. Bessorai, A. Shulman, Y. Snir

Medical Corps, Israel Defense Forces; Depts. of Medicine F and Orthopedics and Emergency Dept., Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Many physicians, civilian as well as in military, feel that some referrals of soldiers to civilian emergency departments are inappropriate and that soldiers should receive medical attention within their military units. We therefore evaluated referrals of soldiers to our emergency department.

707 referral letters from military physicians and the corresponding emergency room discharge letters were evaluated. Most soldiers were referred for mild trauma (45.0%) or miscellaneous diseases (52.9%); 22 (3.1%) were hospitalized.

It appears that some military physicians use the civilian hospital emergency department as a surrogate for an out-patient specialty clinic and for x-ray and laboratory services. This is in contrast to the designated functions of the emergency department which are to provide emergency and trauma services and to evaluate the need for hospitalization of referred patients.

Acipimox as a Secondary Hypolipidemia in Combined Hypertriglyceridemia and Hyperlipidemia

D. Yeshurun, H. Hamood, N. Morad, J. Naschitz

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

32 patients with hypertriglyceridemia, excessive hypertri- glyceridemia, and combined hyperlipidemia, were treated with the nicotinic acid derivative acipimox (Olbetam). First line treatment with bezafibrate, or statins in some with combined hyperlipidemia, had failed. In 10 acipimox was discontinued due to side effects or absence of clinical response. The other 22 completed 6 months of treatment with no side effects.

Acipimox caused a significant 54% decrease in triglyceride levels, a 23% decrease in total cholesterol, and a 12% increase in HDL-cholesterol. LDL-cholesterol was difficult to calculate because of the high triglyceride levels, so no results are presented.

Although acipimox was much better tolerated than nicotinic acid, it also had side effects, but fewer. Acipimox can therefor be used as a second-line drug, mainly in those with combined hyperlipidemia and hypertriglyceridemia.

Use of Unlicensed and Off-Label Drugs in Hospitalized Children

M. Lifshitz, V. Gavrilov, R. Gorodischer

Toxicology Unit, Pediatrics Dept. A, Soroka Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Many drugs used in children are based on pharmacological data obtained in adults. Therefore, many drugs are either unlicensed for use in children or are prescribed outside the terms of the product license (off-label). This pilot study assessed use of unlicensed or off-label drugs in hospitalized children.

Drug orders of patients admitted to a general pediatric ward were reviewed retrospectively in a random sample. Assessment was based on the data of the Physicians' Desk Reference and the Israel Drug Compendium. 80 different drugs and 278 drug orders were written for 92 patients (0.5 months - 11 years old, mean 26.9 months) in 97 admissions. Of these 52.9% were either off-label or unlicensed. Patients received 1 or more unlicensed or off-label drugs in 64.9% of admissions. They were more often off-label than unlicensed. The main reasons for use of off-label drugs were unusual doses and inappropriate age. The main reason for unlicensed drugs was modification of a particular formulation of a licensed drug.

This pilot study indicates that use of drugs in an off-label or unlicensed manner in children is probably quite frequent in Israel. Our data emphasize the need for licensing a large number of drugs for use in children, based on the same scientific principles as in adults. Further collaborative studies in different pediatric centers in Israel, involving different types of pediatric settings (ambulatory and in-hospital), is required to evaluate comprehensively the magnitude of this preliminary finding.

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.

Listeria Monocytogenes Infections - Ten Years' Experience

Tova Rainis, Israel Potasman

Infectious Disease Unit, Bnai Zion Medical Center, and Faculty of Medicine, Technion, Haifa

7 cases of listeriosis were diagnosed here between 1988-1997 (6 in last 3 years), or 2.94/100,000 admissions. 2 elderly patients suffered from meningitis and 2 pregnant women presented with premature contractions, 1 of whom delivered a premature, infected baby. 2 other patients had fever and gastroenteritis.

Listeria monocytogenes was isolated from blood in 4, CSF in 2 and the placenta in 1. It was isolated from those with bacterial meningitis. All patients recovered. Both increased awareness for prevention and better diagnosis are essential to reduce morbidity from this unusual pathogen.

Fulminant Meningococcemia Presenting as a Gastroenteritis - Like Syndrome

A. Hussein, Y. Naschitz, D. Yeshurun

Depts. of Emergency Medicine and of Medicine A, Bnai Zion Medical Center and Bruce Rapport Faculty of Medicine, Haifa

Neisseria meningitidis infection (meningococcemia) is very common throughout the world. It usually presents as meningitis or sometimes pharyngitis. A gastroenteritis-like syndrome, with diarrhea, vomiting and abdominal pain, may occur in children but is very rare in adults. Search of the medical literature revealed only 3 such cases, all in young adults.

We report an 80-year-old woman who presented with fever, diarrhea and abdominal pain. Meningococcus infection was later suspected, and proved by culture. Although treatment was intensive and included ceftriaxone (Rocephin) and garamycin, she did not respond and died 40 hours after admission. We draw attention to the possibility that what is usually a common symptom can be the first presentation of a serious, often fatal condition.

EBV-Related Post-Transplantation Lymphoproliferative Disorder

D. Doron, O. Papo, O. Portnoy, E. Granot

Depts. of Pediatrics, Pathology, and Radiology, Hadassah University Hospital, Jerusalem

We describe a 4.5-year-old girl in whom post transplantation lymphoproliferative disorder was diagnosed 1 year after liver transplantation. She ran a complicated course with multiple organ involvement: respiratory failure which required mechanical ventilation, renal failure, bone marrow depression and severe protein-losing enteropathy.

Multisystem Disease Caused by BCG Imitating Miliary Tuberculosis

I. Tsikonov, D. Yeshurun, J.E. Naschitz

Dept. of Medicine A, Bnai Zion Medical Center and B. Rappaport Faculty of Medicine, The Technion, Haifa

As the prevalence of tuberculosis is on the rise in western countries, we present a 79-year-old man who developed a pulmonary tuberculosis-like syndrome following immunotherapy with BCG for carcinoma of the urinary bladder. The symptoms subsided following 3-drug antitubercular treatment, and the addition of steroids following negative cultures for Mycobacterium tuberculosis. The course of this disease, named BCG-osis, is much more favorable than miliary tuberculosis, even with milder treatment. It is important to keep in mind this phenomenon now that there is increasing treatment of cancers with BCG.

The Challenge of Space-Occupying Lesions in the Iliopsoas Space

Irena Tsikonova, Jochanan E. Naschitz, Simona Croitoru, Elisha Barmeir, Daniel Yeshurun

Depts. of Medicine and Diagnostic Imaging, Bnai Zion Medical Center, and Bruce Rappaport Faculty of Medicine, The Technion, Haifa

Mass lesions in the iliopsoas compartment (MLIPC) are uncommon in patients in departments of medicine and their incidence and etiologies are unclear. In a prospective study we diagnosed various MLIPCs in 7 patients during a 10-year period, representing 0.03% of admissions. Symptoms included abdominal or flank pain (4 cases), pain along the thigh (5), diminished psoas muscle strength (2), fever (2), and hypotension (1). MLIPC was suspected on clinical grounds in 5 cases. In all cases the diagnosis was established by computed tomography (CT). Tissue was sampled by needle biopsy in 4 and on surgery in 1. MLIPCs were caused by hemorrhage (2), infection (2), neoplasia (2) and inflammatory mass (1). Often MLIPCs are life-threatening so their timely diagnosis by early CT scan is important.

Second Degree A-V Block in Graves© Disease

Yoram Singer, Pesach Shvartzman

Dept. of Family Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Cardiac tachyarrhythmias are common in thyrotoxicosis. We report an uncommon case of a 53-year-old woman with Grave's disease who developed second degree A-V block while euthyroid on propylthiouracil. The most likely mechanism is an autoimmune response causing infiltration of the cardiac conduction pathways.

Management of Malignant Bowel Obstruction in Home Care

Menahem Sasson, Pesach Shvartzman

Dept. of Family Medicine, Kupat Holim Klalit and Ben-Gurion University of the Negev, Beer Sheba

Malignant bowel obstruction occurs in about 10% of those with advanced abdominal cancer and in about 25% of those with advanced pelvic cancer. Such patients usually develop nausea, vomiting, constipation, abdominal dilatation and colicky pain. Traditional therapy consists of intravenous fluids and decompression by duodenal tube, gastrostomy or operation but postoperative mortality is high. Treatment requires hospitalization and therefor such patients have not been considered candidates for home care.

Palliative medical techniques can cope with this syndrome and allow home care. Hypodermoclysis, non-prokinetic anti-emetics like haloperidol and scopolamine, octeotride, corticosteroids, and narcotics for severe abdominal pain can alleviate symptoms. Medications can be combined and infused subcutaneously in a syringe driver and patients can remain with their families in their natural environment. Such techniques can give these patients who have short life expectancies reasonable quality of life.

Primary Care Physicians in Israel Compared with European Countries

P. Shvartzman, R. Gross, H. Tabenkin, D. Yuval, M. Grinshtein, B. Wienka

Dept. of Family Medicine, Ben-Gurion University of the Negev, Beer Sheba;

Brookdale Institute, Jerusalem; and Nivel Institute, Maastricht, the Netherlands

This study compares Israeli primary care physicians with those of European countries. In Israel a larger proportion of those in primary care are women. The Israeli physicians see many patients a day, but almost never make home visits. They also report for work the fewest hours a day, but spend 21 hours a month in continuous medical education. (more than Europeans?) The Israeli primary care physician scores high in screening for breast cancer and blood cholesterol level, but very low in the fields of minor surgery and alcohol and smoking prevention, contraception, nutrition counseling and normal pregnancy follow-up. Residency training and education may be inadequate, and more emphasis has to be put on the health system and recognizing environmental influences.

Intra-Osseous Ganglion of Scaphoid and Lunate Bones

M. Kligman, M. Roffman

Dept. of Surgery, Carmel Medical Center, Haifa

We present a patient with intra-osseous ganglion of the left scaphoid and lunate bone. These were excised and a bone graft inserted. 1 year after operation the patient was free of pain, without limitation of wrist motion. Intra-osseous ganglion of the carpal bone is not common and lunate and scaphoid intra-osseous ganglion has rarely been reported. Awareness of this condition may lead to earlier diagnosis and treatment, with satisfactory outcome.