איתן ישראלי

המכון למחקר ביולוגי בישראל, נס ציונה

פרס נובל בפיסיולוגיה או ברפואה לשנת 2000 הוענק במשותף לשלושה חוקרים: ארביד קרלסון, פול גרינגארד, ואריק קנדל, על תגליותיהם בשטח "העברת אותו במערכת העצבים".

במוח האדם יש יותר ממאה מיליארד תאי עצב, המחוברים ביניהם ברשת ענפה ואינסופית של חיבורים. העברת אותות בין התאים נעשית בתיווך של חומרים כימיים, המגשרים על הסינפסות המפרידות בין התאים. לכל תא יכולות להיות אלפי נקודות מגע כאלה עם תאי עצב אחרים. שלושת חתני הפרס גילו תגליות חשובות הקשורות בהעברת האותות בין התאים בתהליך שנקרא העברת אותו איטית. תגליות אלה היו חיוניות להבנת התיפקוד הטיבעי של המוח, וכיצד הפרעות בהעברת אותו אלו עלולות לגרום למחלות במערכת העצבים ולמחלות נפש. בצד מימצאים אלה, פותחו תרופות לטיפול בהפרעות כנ"ל.
 

Retinal Injury Induced by Laser Pointers

D. Israeli, Y. Hod, O. Geyer

Eye Dept., Carmel Medical Center, Haifa

Laser pointers originally designed for use during presentations are ubiquitous and are even sold as toys (such as pens or on key chains) in drug stores. Though reported as safe, the laser pointers still carry the risk of potential damage to the eye. We report a 16-year-old boy with bilateral retinal injury caused by 20-30 seconds of exposure to a laser pointing-device. Immediately thereafter, vision was blurred bilaterally and he noted a central red scotoma in each eye. Symptoms resolved spontaneously within 2 days but the retinal scars remained all during the 10 months of follow-up.

It is clear from our report and 3 other publications that retinal damage can develop from misusing laser pointers. Laser hazards and safety should be stressed for the general public. We recommend that laser-pointers should not be available as toys to children and teenagers.

Screening for Early Detection of Prostatic Cancer

A. Neheman, Y. Shotland, Y. Metz, A. Stein

Dept. of Urology, Carmel Hospital, Lady Davis Medical Center, Haifa

Prostatic cancer (PC) is second only to lung cancer as a cause of cancer mortality in men word-wide. In Israel it is the most common cause of cancer mortality in men, after lung cancer and colo-rectal cancer.

We screened, for the first time in Israel, for prostatic cancer using serum levels of PSA and a digital rectal examination (DRE). The purpose was not only to diagnose PC but also to increase public awareness of the condition.

300 men in the Haifa area who met statistical criteria for early diagnosis of PC participated. They filled a questionnaire regarding risk factors for PC (age, family history (FH) of prostatic and breast cancer, cigarette smoking, alcohol consumption, previous PSA sampling) and were examined. Those who had out-of-ragne, age-related PSA values, or a pathologic DRE underwent trans-rectal ultrasound (TRUS) examination and guided biopsy of the prostate. Those with a positive biopsy for PC underwent radical prostatectomy or radiation therapy.

41 (14.3%) had out-of-range, age-related PSA levels and 10 (3.5%) had a pathologic DRE. 39 (13.3%) underwent TRUS and biopsy and 6 (2.04%) had clinically significant PC, all early stages (Gleason 4-6).

Correlation between age and PSA has been proven statistically significant (p<0.05). Symptoms of urinary tract obstruction and nocturia were related to a high PSA (p=0.035 and 0.002, respectively). Those with PC had at least 1 symptom of urinary tract obstruction; 6 (15.3%) who underwent TRUS and biopsy and a FH of prostate cancer. However, no subject with a FH of PC had biopsy-proven cancer. Those with PC had PSA values from 4.9 to 31.8 ng/ml (9.6 median). Age-related PSA had a positive predictive value of 17.1%.

Results of our annual screening for early detection of PC using age-related PSA, and DRE are encouraging: cases detected were clinically significant and treatable. It would appear that screening for PC will result in decreasing the incidence of metastatic cancer and therefore mortality. 
 

A Molecular Method of Diagnosis of Congenital Adrenal Hyperplasia

Shoshana Israel, Chaim Brautbar

Tissue Typing Unit, Hadassah Medical Center, Jerusalem

Congenital adrenal hyperplasia (CAH) is caused mainly by deficiency of the 21-hydroxylase enzyme. The disease may appear in the classical salt-losing, simple virilizing forms or as a mild, nonclassical form. 21-hydroxylase is encoded by the CYP21B gene on the short arm of chromosome 6, in the midst of the human leukocyte antigen (HLA) complex, between HLA Class I and Class II regions.

We describe a method for identifying mutations in the CYP21B gene. It is based on amplification of the gene using the polymerase chain reaction and identification of mutations with sequence-specific oligo-probes. The mutations identified were: V281 and P30L responsible for nonclassical CAH, and I2 splice, Q318X, I172N, cluster E6, and a deletion including 8bP in the third exon (8bP del) responsible for the classical form of CAH.

We also analyzed 2 families affected with the classical form of CAH which demonstrate possible complications in genotyping. Typing for HLA haplotypes can be helpful in certain cases, as demonstrated in 1 of the families presented. In this case it was necessary to distinguish between 2 possible genotypes: 1 with the mutations in tandem on 1 chromosome and the other with the mutated genes on both chromosomes. HLA haplotyping enabled the assignment of the mutations to the relevant chromosomes and thus allowed correct genetic counseling.

The other family demonstrated the importance of CYP21B genotyping in individuals with the nonclassical form of CAH. This form may consist of 1 mild and 1 severe mutation, representing a serious potential for transmitting the classical form of CAH.

Assisted Reproductive Technologies Reported in Israel National Registry, 1995 and 1996

V. Insler, O. Gonnen, D. Levran, Y. Lotan, B. Fish, G. Potashnik, A. Kogosovsky, R. Ron-El

Committee of the Israel National Registry Assisted Reproductive Technologies*

National registration of the results of assisted reproductive technology (ART) is maintained by many countries. The Israel Committee for Registry of ART asked 19 in-vitro fertilization (IVF) units in 1995 and 20 in 1996 to report on their activities and results.

Data were collected by questionnaires and analyzed by computer. The most common ovarian stimulation was the combination of GnRH agonist and gonadotropins. There were 10,89 treatment cycles in 1995, of which 45% were with intracytoplasmic sperm injection (ICSI). In 1996, of 12,72 cycles, 54% were with the ICSI procedure. Embryos were transferred into the uterine cavity in 90% of the conventional IVF cycles and in 95% of the ICSI cycles. The overall pregnancy rate was 22% per embryo transfer in the conventional IVF and ICSI cycles. The delivery rate was 13.7% and 15.4% per embryo transfer in the conventional IVF and ICSI cycles, respectively. The rates for abortion and tubal pregnancy were 24% and 1.3%, respectively.

These results are better than in previous years and are comparable with results in some western European countries. Efforts are being made to convert the registry into a real-time computerized system.

Committee of the Israel National Registry of ART.

Folic Acid for Preventing Neural Tube Defects

Ziv Gil, Adi Aran, Orna Friedman, Liana Beni-Adani, Shlomo Constantini

Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba; Division of Pediatric Neurosurgery, Dana Children's Hospital, Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv

Spina bifida and anencephaly are the most common, serious malformations in neural tube defects (NTD). Randomized trials in the last 2 decades have demonstrated that folic acid, 0.4 mg/d, reduces the incidence of NTD by more than 50%. We investigated the use of folic acid and multivitamins containing folic acid in childbearing women.

Of 221 women interviewed, 67 (30%) regularly took pills containing 0.4 mg folic acid. Women with higher educational levels were more likely to take multivitamins with folic acid than were the less educated (p=0.05). Of the women who took folic acid, only 5 (7.5%) used separate folic acid tablets, before and during their pregnancy. The rest used multivitamins containing folic acid. The 5 women who took folic acid separately were college-educated and nonreligious, and they took multivitamins in addition (p>0.05).

Of the women interviewed, 58 (26.2%) were Bedouin of the Negev. 24 (41.4%) of them took pills containing folic acid on a regular basis. This percentage is higher than that in the Jewish women in the study who took folic acid for prevention of NTD (17%; p=0.038).

Most of the women took folic acid after the first trimester. Only a minority took daily periconceptional folic acid. Multivitamins containing 0.4 mg of folic acid were more popular than folic acid tablets alone. This study emphasizes the need for continuing efforts to increase consumption of folic acid and awareness of its benefits among women of childbearing age.

Regulation of Natural Medicines in Israel and Abroad

T. Lavy, B. Haran, J. Shemer, S. Shani

Israel Ministry of Health, Pharmaceutical Policy and Economics Unit; Israel Center for Technology Assessment in Health Care; Gertner Institute for Epidemiology and Health Policy Research; Sackler Faculty of Medicine, Tel Aviv University

Hand-in-hand with the public's growing interest in health care, there has been an increasing demand for natural health products considered both safe and medically effective. But many such products have not been shown to meet efficacy and safety criteria and therefore can not be registered as pharmaceuticals. On the other hand, it is quite clear that some products do have pharmacological activity and are being used for therapeutic or preventive effects.

In Israel, the marketing rules for food or dietary supplements prevent their manufacturers from claiming medicinal/healing properties that the product might have, and allow only limited health statements. But great demand for these products has created massive publication attributing medicinal indications for products whose quality, efficacy and safety have neither been examined nor proven according to accepted medical criteria.

We review the regulation and supervision of natural health products in Israel and other developed countries and find a broad range of opinions about natural health products. They range from acceptance as conventional drugs reimbursable by the health insurance, as in Switzerland and Germany, to their status as dietary supplements requiring no significant authorization or supervision, as in the USA.

Analysis of the current situation in Israel and the western world would indicate that some natural health products do possess pharmacological activity and therefore manufacturers should be allowed to make limited claims for specified therapeutic properties. A stricter set of registration regulations are needed for proof of safety, efficacy and quality of these products, but more lenient than those for registering a pharmaceutical product.

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.

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.

רונית חיימוב-קוכמן¹, ראובן ברומיקר², אריאל מילויצקי¹

¹מחלקת נשים ויולדות ²והמחלקה לטיפול נמרץ בילוד, בי"ח הדסה הר הצופים, הפקולטה לרפואה, האוניברסיטה העברית, ירושלים

Israel Hospital Pharmaceutical Services: A National Survey 

S. Livny, A. Hammerman, S. Shani, J. Shemer

Hiliel Yaffe Medical Center, Hadera; Israel Center for Technology Assessment in Health Care; Gertner Institute, Tel HaShomer; Dept. of Internal Medicine, Sheba Medical Center, Tel HaShomer; and Sackler School of Medicine, Tel Aviv University

Results of a 1996 survey of hospital pharmaceutical services in Israel are presented. A questionnaire was mailed to 46 pharmacy directors in Israel hospitals of which a total of 33 were returned (72%).

The main services provided at hospital pharmacies are production of pharmaceuticals and inventory management. The pharmacy directors estimated that more then half of their pharmacists' time was spent on technical work that did not need their academic, professional knowledge. In Israel general hospitals there are on the average 1.23 full time pharmacist positions per 100 hospital beds and 1.09 positions for other pharmacy employees.

A similar survey carried out in the United States showed an average of 7.4 pharmacists per 100 hospital beds. Pharmacists there have broad clinical roles which, in general Israeli pharmacists do not have.

Computer systems are used in our pharmacies mainly for inventory management. About half of the directors did not think that the location, structure and furnishings of their pharmacy were appropriate for its role.

Under current conditions, Israel hospital pharmacies are not organized to provide pharmaceutical services beyond inventory management and pharmaceutical production. Appropriate budgets and personnel are required to develop clinical pharmacy services at Israel hospitals. This would lead to improved quality of drug treatment and cost-containment and would allow pharmacists to exploit their knowledge, skills and training that under the current system, are only partially utilized.

Military Psychiatry in Israel: a 50-Year Perspective 

Avi Bleich

Tel Aviv-Souraski Medical Center and Sackler Faculty of Medicine, Tel Aviv University

The history of military psychiatry in Israel may be divided into 2 main periods. The first extended from the War of Independence in 1948, through the Sinai, Six Day and Yom Kippur Wars. Its outstanding feature was avoidance of the issue of combat stress reaction (CSR). The Yom Kippur War made the recognition of CSR inescapable, assisted in breaking up denial, and served as a stimulus for development of the next phase of the system.

This second phase was characterized by impressive progress in all areas of military psychiatry. The rich experience accumulated during the wars, together with the assimilation of a research culture which began blooming, especially in the wake of the Lebanon War, aided the development and crystallization of concepts related to combat and non-combat military psychiatry alike. The build-up of the mental health organization overlapped field deployment of the Medical Corps.

The Gift of Breastfeeding 

Dorit Nitzan Kaluski, Alex Leventhal

Dept. of Nutrition, Public Health Services, Israel Ministry of Health, Jerusalem

Breast milk is the optimal food for infant growth and development, the prevention of infectious diseases and mother- child bonding. From the economic perspective, breastfeeding is cost-effective both for the family and society as a whole. The Israeli Ministry of Health encourages breastfeeding as the exclusive source of nutrition for infants in the first 4-6 months of life, with gradual addition of complementary foods thereafter. The promotion of breastfeeding in Israel requires comprehensive national activity with involvement of all the stakeholders. This includes implementation of the International Code of Marketing of Breast Milk Substitutes and joining the international "Baby Friendly Hospitals" project. Knowledge of breastfeeding should be spread, health professionals should be encouraged to become agents of change, support by breast counselors should be encouraged, post-delivery vacations from work should be prolonged and empowerment of women implemented.

Family Physicians' Attitudes to Clinical Guidelines for Treatment of Diabetes 

Sasson Nakar, Shlomo Vinker, Tal Baro-Aloni, Eliezer Kitai

Dept. of Family Medicine, Rabin Medical Center and Sackler Faculty of Medicine, Tel Aviv University

Clinical guidelines are systematically developed statements designed to help practitioners and patients make decisions about appropriate health care for specific clinical states. Attitudes of family physicians to clinical guidelines for treating diabetes and guidelines in general were evaluated from anonymous questionnaires answered by physicians participating in continuous medical education throughout the country (May-June 1998). The questionnaire dealt with attitudes to the recently published specific guidelines for treating the diabetic patient and overall perception of the efficacy of clinical guidelines.

293 family physicians, aged 40.2‏7.0 responded (83%). 93.5% appreciated the guidelines and thought them applicable. Most (83.7%) reported the guidelines to be of help in their daily work; 31.4% said they were oversimplified; a quarter said they aimed main at containing costs. Most respondents preferred written guidelines of up to 5 pages.

In view of our results, attention can now be turned to developing ways to implement the guidelines. To improve adherence, they need to be short and the rate of publication of new clinical guidelines should be slowed.