In Vitro Interferon-Gamma Release in Diagnosis of Cutaneous Adverse Drug Reactions

S. Halevy, A. D. Cohen, N. Grossman

Dermatology Dept, Skin Bank and Investigative Dermatology Laboratory, Soroka University Medical Center and Faculty of Health Sciences; Ben-Gurion University of the Negev, Beer Sheba

Diagnosis of cutaneous adverse drug reactions is an accepted terminology. Is a challenge. Drug-specific T-cell clones (CD4+ or CD8+), with a Th1- or a Th2-type cytokine-release pattern, may be generated from the peripheral blood in CADRs. In vitro drug-induced cytokine-release suggests a drug-specific immune response, and may implicate the drug as a possible inducer of the skin reaction.

We evaluated the diagnostic role of in vitro drug-induced interferon-gamma (IFN-γ) release from peripheral blood lymphocytes in patients with CADRs. We studied 22 patients with CADRs following intake of 45 drugs (1-4 drugs per patient). Drugs were classified into 3 categories of suspicion. 17 patients who took 39 drugs of the same type (1-4 drugs per patient) without developing adverse reactions, served as controls. In vitro drug-induced release of IFN-γ from peripheral blood lymphocytes, following in vitro challenge with the unmodified drugs, was evaluated.

The mean IFN-γ increase following 45 drug tests (60.8±85.2%) was higher (p<0.05) than in controls after 39 drug tests (30.1±27.7%). Significance was greater (p<0.005) when the mean IFN-γ increase for the 24 highly suspected drugs (75.1±93.4%) and that for the controls were compared.

This study suggests that the in vitro drug-induced IFN-γ release test may serve as a diagnostic tool in CADRs.

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.

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.

Laparoscopic Cholecystectomy - 1,000 Procedures in a Surgical Department

Uri Freund, Ami Mayo, Ivan Schwartz, David Neufeld, Haim Paran

Dept. of Surgery A, Meir Hospital, Kfar Saba; and Sackler School of Medicine, Tel Aviv University

The first 1,000 laparoscopic cholecystectomies performed in our department were reviewed. There was no operative mortality; conversion to open cholecystectomy was necessary in 2%. In the last 600 cases the rate of conversion had decreased to 0.5%. There was common bile duct injury in 0.3%, with the injuries identified during primary surgery. This clinical experience is consistent with previous studies, which proved that laparoscopic cholecystectomy is safe and should replace open operation as the procedure of choice. 

Diabetes and Premature Delivery: Etiology and Risk Factors 

Avi Beigelman, Arnon Wiznitzer, Ilana Shoham-Vardi, Hilel Vardi, Gershon Holtcberg, Moshe Mazor

Depts. of Obstetrics and Gynecology and of Epidemiology and Health Services Evaluation, Soroka Medical Center and Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheba

Preterm birth is the leading cause of perinatal morbidity and mortality, while preterm labor and delivery in diabetes mellitus (DM) carries an increased risk of perinatal complications. We investigated the hypothesis that DM (gestational and pregestational) is an independent risk factor for preterm birth and evaluated the hypothesis that the risk factors for preterm birth in diabetics are different from those in non-diabetics.

The study population consisted of all singleton deliveries at this hospital between 1990-1997. Excluded were those of mothers who had not had prenatal care, or who had only partial care or multiple gestations. There were 3 subgroups: 834 women with pregestational DM, 3,841 with gestational DM, and 66,253 non-diabetics.

The combined spontaneous and induced preterm delivery rate was determined in each subgroup. Potential risk factors for spontaneous preterm deliveries were assessed by a univariate model. A logistic regression model was used to assess the unique contribution of DM (gestational and pregestational) to preterm delivery in the presence of the other risk factors, and to compare risk factors for preterm delivery between subgroups.

The prevalence of spontaneous preterm delivery was: 7.1% in non-diabetics, 10.0% in those with gestational DM and 25.5% in those with pregestational DM. When adjusted by a multivariate model for other risk factors for preterm delivery, DM still remained an independent risk factor for spontaneous preterm delivery (gestational DM: odds ratio 1.28, 95% CI: 1.1-1.48; pregestational diabetes: odds ratio 3.4, 95% CI: 2.65-4.36).

The main difference in risk factors for preterm birth between the 3 subgroups was the amount of amniotic fluid. Polyhydramnios was an independent risk factor for preterm delivery in non-diabetics and in pregestational DM, but not in gestational DM. On the other hand, oligohydramnios was associated with a higher risk for preterm delivery only in gestational DM compared to non-diabetics.

DM (gestational and pregestational) is an independent risk factor for spontaneous preterm delivery. Polyhydramnios is an independent risk factor for preterm delivery in pregestational but not in gestational DM. Oligohydramnios is a greater risk factor for preterm delivery in gestational DM compared to non-diabetics.

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.

Causes of Blindness in Israel 

Y. Hod, Y. Corcia, Y. Yassur, O. Geyer

Depts. of Ophthalmology, Carmel Medical Center, Haifa and Rabin Medical Center, Petah Tikva; Israel Ministry of Labor and Social Affairs, Jerusalem; and Rehabilitation Services Administration, Services for the Blind

Of the world population, 38 million are blind and another 110 million are visually impaired. Even in the developed countries there are 3.5 million who are blind.

This study of blindness in Israel is based on the National Blind Registry. At the end of 1998, 15,937 were registered as blind, 0.3% of the total population; 776 (5%) of them were 18 years old or younger; 6,426 (40%) 18-65 years old; and 8,735 (55%) 65 years or older.

The leading causes of blindness in Israel are glaucoma (2,074, 13%), macular degeneration (1,954, 12%) and diabetes mellitus (1,680, 11%). Since glaucoma and diabetes, and to a lesser extent glaucoma, respond to treatment, blindness could have been avoided in most cases. National screening programs for early diagnosis and treatment of these diseases would reduce prevalence of the newly blind.

Pediatric Research in an Office-Setting Network

Zahi Grossman, Ernesto Kahan, Samuel Gross, Shai Ashkenazi, Itamar Shalit

Kupat Holim Maccabi, Tel Aviv; Israel Ambulatory Pediatric Association; Dept. of Family Medicine, Tel Aviv University; and Schneider Children's Medical Center, Petah Tikva

Pediatric care in the community is gradually replacing traditional care in hospitals. Despite that, research activity in the community setting is minimal due to objective difficulties. These are mainly constraints of time, office work and lack of research-supporting logistics. In the past decade, throughout the world, primary physicians interested in research have grouped together and formed research networks. The aim of such networks is to support and promote research in the community.

An Israel Pediatric Research in Office-Setting network (IPROS) was established 2 years ago by the Israel Ambulatory Pediatric Association (IAPA). Today, there are over 140 pediatricians listed in IPROS, representing the heterogeneous composition of pediatricians in Israel. The network's policy is defined by a joint steering committee. The committee is composed of IAPA representatives, senior network members and Schneider Hospital senior investigators. The research subjects are diverse, and represent common practical issues.

Effective intra-net communication is vital to the existence of the network, and is accomplished by 3 modalities: 1) semiannual updates by mail, 2) e-mail, using an electronic mailing list to facilitate connection between members, 3) semi-annual meetings. Research budgets are derived from public sources like the Ministry of Health and IAPA, and private sources such as pharmaceutical companies. The administration of the network is supported by Schneider Children's Medical Center, and financed by IAPA.

Liver Surgery - Five Years of Experience

Franklin Greif, Moshe Rubin, Eitan Mor, Israel Nudelman, Arnold Sihon, Arie Figer, Alex Belinki, Shlomo Lelcuk

Hepatobiliary Unit and Depts. of Surgery B, Transplantation, Oncology and Radiology, Rabin Medical Center (Beilinson Campus) and Sackler School of Medicine, Tel Aviv University

Major hepatic resections have been associated with significant morbidity and mortality. In the past decade or so this has changed and such procedures are now done in increasing numbers. In the past 5 years we operated on 129 patients with benign or malignant hepatic lesions (75 females, 54 males; age-range 14-84). the reason for surgery was malignancy in 94 (72.9%) and benign lesions in 35 (27.1%). The most common indication for surgery was liver metastases secondary to colorectal cancer in 45% of all patients or 61.7% of those operated for malignancy. Primary liver cancer was the cause for liver resection in 13.2% of all patients or 18.1% for those with malignancy. Of the 35 patients with benign lesions the leading causes for surgery included: giant cavernous hemangioma, simple liver cysts, echinococcus cysts and focal nodular hyperplasia (11%, 22.8%, 20% and 14.3%, respectively).

76 patients underwent anatomical resection and 63 had either a nonanatomical resection or a different operation. Among the former the most common procedure was right hepatectomy (36) and among the later a nonanatomical resection equal to 1-3 Couinod segments (44). Operating time ranged from 55 min. to 8:41 hours with a mean of 3:31‏1:37. Mean hospital stay was 8.7‏5.8 days and 86.8% received between 0-2 units of blood. Overall mortality was 6.2% and 31.2% of the fatalities had cirrhosis. Overall mortality in noncirrhotic patients was 2.6%. The complication rate was 16.3% and only 7 patients (4.4%) were hospitalized in the intensive care unit. This indicates that major liver resections can be done safely, with morbidity and mortality similar to that of other major abdominal operations. 

Quality Assurance in the Mental Health Department of the Israel Defense Forces

Mordechai Mark, Moshe Z. Abramowitz, Orna Intrator, Ehud Bodner, Rami Shklar, Haim Y. Knobler

Mental Health Department, Medical Corps, Israel Defence Forces

A review of quality assurance in the mental health department of the Israel Defence Forces allowed the examination of certain unique elements of quality control which pertain to the military. These include the psychiatric medical board, the computerized documentation of appointments and sessions with soldiers, the psychiatric hospitalization database, control systems implemented in the draft boards, peer-review boards and supervision, and a special officer in charge of handling outside consultations and queries. There were other components of quality assurance and control as well. These instruments are vital in a dynamic system constantly striving to improve clinical performance.

Future plans include the continued use and expansion of quality control boards, the inclusion of quality assurance in the curriculum of mental health officers, and the use of clinical guidelines in working with soldiers. All of this is in keeping with the principle of continuous quality improvement, with the aim of viewing the soldier in need of help as a client.

The Israel Teratogen Information Service: A 10-Year Report 

A. Ornoy, S. Shechtman, J. Arnon

Hebrew University - Hadassah Medical School and Israel Ministry of Health, Jerusalem

The Israel Teratogen Information Service (TIS) was established 10 years ago with the help of the Ministry of Health and the Hebrew University-Hadassah Medical School. During these 10 years we have had 20,631 calls. We describe the results of our experience in counseling.

There was a gradual increase in the number of calls, which in 1997 reached 4,447. Most calls (84.5%) were during pregnancy, while 12% were prior to pregnancy. In 75.7% the calls were due to drug exposure during pregnancy; 10.9% were due to exposure to X-rays; there was maternal infection in 6.6% and in 5% immunization during pregnancy. The callers were: physicians in 46.6%, nurses 18.9%, pregnant women 39.5%, and 4.8% others.

In 76.6% there was no additional risk to the embryo or fetus and in 17.4% there was a small additional risk of less than 1%; a significant additional risk to the fetus was expected in only 6%. In 3625 pregnant women with known outcome there were 8.9% spontaneous and 9.2% induced abortions. Of the 2968 live-born children, 2.3% were malformed, a rate similar to that among controls.

The information provided by the TIS alleviated the fears most pregnant women have, and reduced unnecessary terminations of pregnancy planned because of unjustified fear of the teratogenic effects of agents to which women were exposed. It reduced the number of children born with congenital anomalies, since pregnancies were interrupted whenever there was a high risk for congenital anomalies.

Nonpenetrating Deep Sclerectomy

Orna Geyer

Ophthalmology Dept., Tel Aviv-Sourasky Medical Center

This is the first report from Israel of nonpenetrating deep sclerectomy (DS), a new operation for the surgical management of glaucoma. It facilitates ocular fluid drainage without entering the eye. It involves performance of a conjunctival flap and creation of a 565 mm superficial scleral flap. A deeper scleral flap is dissected off the scleral bed together with the roof of the canal and corneal stroma, leaving behind the wall of the canal and membrane. Aqueous will flood the dissected area. A collagen device is then sutured to the scleral bed, the superficial scleral flap sutured into position and the conjunctiva closed. With this procedure, the surgeon can avoid the common complications of conventional glaucoma surgery.

We report a 6-month follow-up of 15 patients after DS. Mean preoperative intraocular pressure was 26.7+2.5 mm Hg, which decreased to 15.5+4.7. After 6 months there was no change in visual acuity after surgery. DS is associated with good middle-term intraocular pressure control and a low rate of postoperative complications. It is therefore a good alternative to standard glaucoma surgery.

Botulinum Toxin Injection Effective for Post-Peripheral Facial Nerve Palsy Synkinesis

Samih Badarny, Nir Giladi, Silvia Honigman

Dept. of Neurology, Carmel Medical Center, Haifa; and Movement Disorders Unit, Dept. of Neurology, Tel Aviv Medical Center

Facial synkinesis is an involuntary activation of muscles innervated by the zygomatic or mandibular branche of the facial nerve in conjunction with voluntary activation of the other branch. It appears frequently after recovery from peripheral facial nerve paralysis. We report 10 patients with facial synkinesis following Bell's palsy with a mean duration of synkinesis of 7±4 years before treatment with periorbital injections of Botulinum toxin type A. 9 had marked subjective and objective improvement starting a few days after injection andlasting 4-9 months. The results suggest a useful treatment option for post-Bell's palsy facsynkinesis with Botulinum toxin type A.

Should Physical Restraints be used in an Acute Geriatric Ward?

Svetlana Barazovski, Arnold Rosin

Geriatric Dept., Shaare Zedek Medical Center, Jerusalem

A prospective study was carried out in an acute geriatric ward to determine the incidence of the use of physical restraints, the reasons for using them and the consequences. Over a period of 8 months an independent observer documented all cases in which a restraint was used and followed them until it was removed. A questionnaire was submitted to the nurses as to why they applied the restraints. 16% of patients had some form of restraint applied, in 2/3 of them for up to half of their stay in the ward. In over 90% of those restrained, functional (Barthel) and cognitive (mini-mental) scores were between 0-5. In unrestrained patients, the functional score was 0-5 in 79% and the cognitive score 0-5 in 72%. The main reason for applying restraints, usually sheets or body binders, was to prevent the patient from falling out of, or slipping from chairs, rather than to stop them from rising out of them. Other important reasons, which overlapped, were to prevent the patient from interfering with nasogastric tubes, catheters, and IV cannulas, each in 1/3 of the group. Restraints were discarded when deterioration did not allow the patient to sit out of bed, to decrease agitation, to allow enteral or parenteral treatment, and in 12%, when there was supervision by the family. Of 33 families interviewed, none opposed application of restraints, and most left the decision to the responsible ward staff. We conclude that restraints cannot be avoided in some acutely ill, old patients with severe physical and mental dysfunction. However, ways should be sought to minimize their use, as recommended in the literature, by demanding from the staff a specific reason, signed agreement of a physician, close follow-up, and favorable environmental conditions such as suitable chairs, occupational activity, and staff cooperation in removing the restraints.

Effect of the Yom Kippur Fast on Parturition

A. Wiser, E. Maymon, M. Mazor, I. Shoham-Vardi, T. Silberstein, A. Wiznitzer, M. Katz

Depts. of Obstetrics and Gynecology and of Epidemiology, Soroka Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Food-withdrawal has been proposed as a possible mechanism for initiating the onset of labor in animals and humans. The hypothesis was based upon the reported increase in deliveries of infants during the Yom Kippur fast. We studied the effect of the fast on full term deliveries of Jewish women, with non-fasting Bedouin women as controls (1988-1995, 1,313 Jewish and 1,091 Bedouin deliveries). To determine the effect of Yom Kippur itself, delivery rates on Sukkot and Yom Kippur were compared in both groups. The mean delivery rate in the Jewish population was significantly higher during Yom Kippur and the day after, than during the 7 days before Yom Kippur (15.1±5.1 and 14.6±4.7 vs 10.7±3.5, p<0.04 and p<0.01, respectively). There was an increase in delivery rate during the 6 hours before the end of the fast. In the Bedouin women there were no changes in delivery rate during any of these periods. There were no significant differences in the rates of deliveries during the Sukkot festival between Jewish and Bedouin women. We conclude that fasting is associated with a significant increase in the rate of deliveries at term.