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.

Intraventricular Hemorrhage in Full-Term Neonates

S. Menascu, A. Levitas, A. Golan

Pediatrics B Dept., and Newborn and Preterm Dept., Soroka Medical Center and Ben-Gurion University of the Negev, Beer Sheba

Intraventricular hemorrhage in full-term neonates is rare; it may develop without any clinical signs. Its cause is not fully understood although some risk factors have been identified. A higher index of suspicion would ensure earlier diagnosis and treatment, which might reduce the rate of severe complications. We describe 2 cases in full-term neonates.

אליהו לויטס

היחידה לפוריות והפריה חוץ-גופית, החטיבה למיילדות וגינקולוגיה, ביה"ח האוניברסיטאי סורוקה, הפקולטה למדעי הבריאות, אוניברסיטת בן-גוריון בנגב, באר-שבע

יותר ויותר מתבהר הצורך לאבחן ולטפל בחוסר הביוץ. אי-הפוריות היא רק תוצאה אחת, קביעת האבחנה וטיפול בתאם יכולים למנוע תופעות שליליות נוספות לבריאות האשה. תוצאות של חוסר ביוץ כוללות ירידה בצפיפות העצם, ירידה בחימוד (ליבידו), תופעות בלתי רצויות בעור ובשיער, שיגשוג בלתי מבוקר של רירית הרחם (endometrium), מצב קרדיוואסקולרי מעורער ושינויים פסיכולוגיים ופסיכיאטריים. התוצאות הסוציאליות והפסיכוסוציאליות של חוסר הביוץ לא תמיד בתודעתנו, למרות חשיבותן הרבה. על כן, כדי לייעץ נכון למטופלת, דרושה אבחנה מדויקת, ככל האפשר.

המושג הבסיסי להבנת הפתוגנזה של הפרעות ביוץ קשור בהבנת העובדה, שהפרשה פעימתית מתאימה של GnRH (Gonadotropin Releasing Hormone) מההיפותאלאמוס במוח קובעת את מועד הביוץ והווסת. פעימות של GnRH מהירות או איטיות מדי יגרמו לחוסר ביוץ או להרס הגופיף הצהוב השחלתי טרם זמנו...
 

Pulmonary Adenocarcinoma in Myasthenia Gravis - Auto-Immunity and Late Development of Malignancy

Yitzhak Rosen, Yair Levy, Yehuda Shoenfeld

Dept. of Internal Medicine B, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

We report a 75-year-old man with myasthenia gravis for many years, who was hospitalized because of cough, fever, and dyspnea. Chest x-ray revealed a bilateral pleural effusion. Adenocarcinomatous cells were found in the pleural fluid. Computerized tomography of the chest showed widespread pulmonary dissemination of the tumor.

The relationship between myasthenia gravis, an autoimmune disease involving the motor end-plate, and malignancy (thymoma) has been widely recognized. Current literature documents few reports of lung malignancies with concurrent development of myasthenia gravis. A tentative explanation, based on current research, is provided for the possible role of myasthenia gravis and the late development of lung cancer. Moreover, a model for the autoimmune phenomenon and the development of late malignancies will be provided with explicit explanations. It is important to search for occult, developing malignancies in newly diagnosed autoimmune diseases.

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.

רונית חיימוב-קוכמן¹, ראובן ברומיקר², אריאל מילויצקי¹

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

Acute Ischemia of the Lesser Gastric Curvature 

D. Czeiger, A. Ariche, G. Shaked, N. Sion-Vardi, I. Levi

Trauma Service, Dept. of Surgery, and Pathology Institute, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheba

The rich blood supply of the stomach protects it from ischemia and necrosis. Acute gastric ischemia, an emergency with high mortality, is rare. Atherosclerosis is the leading cause of acute ischemia, and the lesser curvature of the stomach is more vulnerable due to its relatively lesser blood supply. Reduction in gastric blood supply usually presents as chronic disease characterized by gastritis, gastric ulcer, or gastroparesis.

Gastroscopy can identify lesions of the gastric mucosa, and angiography demonstrates occluded vessels. Treatment of acute gastric ischemia is surgical, with total gastrectomy preferred over partial resection.

Incidence of Insulin Dependent Diabetes in Youth in Israel 

Israel IDDM Registry Study Group

Recent reports from different countries have shown an increasing incidence of insulin-dependent diabetes mellitus (IDDM, type I diabetes). In Israel, several surveys of the incidence of IDDM have been conducted. During 1996, a national juvenile diabetes register was founded by specialists in endocrinology, and the Israel Center for Disease Control (ICDC).

This is the first report of the national incidence of IDDM in the 0-17 year age group in Israel. New cases of juvenile diabetes were reported using an anonymous form. The ICDC was responsible for data collection, control and statistical analyses.

During 1997, 162 new cases of diabetes mellitus were reported in the age group 0-17, 154 of them diagnosed as IDDM. The annual incidence in the total population of Israel in 1997 was 7.7/100,000. Age-specific incidence was 7.3/100,000 in boys and 8.1 in girls. A family history of IDDM was found in 14.3% of the cases. Incidence was higher for Jews (9.2/100,000) than Arabs (3.6/100,000). Among Jews, children whose fathers were born in Yemen had the highest incidence and those born to fathers born in Israel the lowest incidence.

IDDM incidence rates for 1997 are higher than reported in previous surveys. It will be possible to draw conclusions regarding possible trends in incidence from data to be gathered in the next few years.

Prioritizing Suspected Diagnosis of Both Brain and Abdominalinjuries: Is it a Problem?

Leon Levi, Moshe Michaelson

Dept. of Neurosurgery and Trauma Unit, Rambam Medical Center, Haifa

Current guidelines for management of suspected head and abdominal injuries are based on retrospective studies like that of Wisner & al, Following a recent review in this journal by Y. Kluger & al, which was based on non-Israeli data, we decided to define the current status at our trauma center.

We compare our data of 18 months of hospital admissions for acute trauma in which head CTs were done with those of 5 articles advocating specific protocols for decisions in pre-laparotomy diagnosis.

In the 861 cumulated cases, compared with the 800 of Wisner & al, craniotomy was required in 15% vs 7% (p<0.05); laparotomy was much less frequent, 2.7% vs 12.9% (p<0.05). The chance of finding a case requiring both craniotomy and laparotomy was 1 in 300.

As the clinical condition of multiple trauma involving the head and abdomen is becoming less frequent and includes diverse situations, a comprehensive algorithm might be inaccurate. Good clinical judgment of the clinician and teamwork are therefor preferable.

Early Detection of Glaucoma by a Mobile Unit

S. Kurtz, M. Goldenfeld, S. Melamed

Sam Rothberg Glaucoma Center, Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer

Glaucoma, the third leading cause of blindness in the western world, is characterized by painless, gradual loss of visual fields which may lead to severe visual impairment or even blindness. In 4 years of operation of a mobile glaucoma unit for screening and early diagnosis of glaucoma, 10,037 subjects aged 18-95 years were screened (4504 women, 45%); 55% were under 50 years (Graph 1).

Ocular hypertension was diagnosed in 8.0%; primary open angle glaucoma (POAG) in 0.8%, with 2/3 already under treatment, the rest newly diagnosed. Pseudo-exfoliative glaucoma was diagnosed in 0.2%; only 2 cases had closed angle glaucoma; 91% of those screened were normal (Fig. 4; age stratification, Graph 3).

POAG increased with age, from 0.2% in those under 40 years to 10% in those over 80; POAG was more common in men, but OHT was similar in both sexes (6.0% vs. 5.3%). There was no correlation between incidence of POAG and place of work except in the Sorek Nuclear Center (1.9% vs. 0.8%, p=0.11). Other conditions significantly more frequent in POAG than normals were diabetes mellitus (x 2.5), systemic hypertension (x 4), myopia (x 2) and history of intraocular surgery (x 6).

Introduction of Routine Hepatitis Immunization in Israel 

Emilia Anis, Alex Leventhal, Malvina Roitman, Paul E. Slater 

Notification of hepatitis A, which is endemic in Israel, has been compulsory since the establishment of the State. From 1992-98 an average of 2,600 cases were reported annually. Many infections are asymptomatic and mild, especially in children. In general, severity increases with age; in Western countries the case fatality rate is 1.5/1,000 among children less than 5 years old and 27/1,000 among those over 50. Until 1987 incidence in Israel was higher in Jews than in non-Jews, but since 1988 incidence has been about 50% higher in non-Jews.

Among Jews highest age specific rates shifted from children 1-4 years old to children 5-9 years old in 1970, and in non-Jews in 1989. Improved sanitary conditions and personal hygiene have reduced very early childhood exposure and hence increased the proportion of susceptible older children and adults, in whom symptomatic disease is more prevalent.

Israel is the first country in the world to include hepatitis A vaccine in its routine immunization schedule. The vaccine is given in 2 doses: at 18 months and 24-30 months of age, and there will be epidemiologic and serologic follow-up. A significant decrease in hepatitis A morbidity is expected in small children within 5 years. The percentage of reported cases in older children and in adults is expected to increase, although the absolute incidence among these groups will decrease.
 

Dept. of Epidemiology and Public Health Services, Israel Ministry of Health, Jerusalem

Transarterial Oil Chemoembolization for Hepatocellular Carcinoma 

Izhar Levy, Anthony Verstandig, Talia Sasson, Dana Wolf, Ilia Krichon, Eugin Libson, Pinchas Levensart, Orit Papo, Oded Yurim, Ahmed Id, Daniel Shouval

Division of Medicine, Liver Unit and Invasive Radiology, Radiology, Pathology and Surgery Depts., Hadassah University Hospital, Ein Kerem, Jerusalem

Hepatocellular carcinoma (HCC) is a common malignancy with a grave prognosis. Most patients have both the malignant tumor as well as hepatic cirrhosis. Liver transplantation or hepatectomy are considered the only curative procedures, but can be applied in fewer than 10% of patients. In recent decades the most common treatments of HCC are transarterial chemoembolization with oil (TOCE) and percutaneous ethanol injection (PEI). We summarize our retrospective study of 100 patients (mean age 64) 3‏ treated by TE.

In 271 procedures between 1989-1998, in 16 patients hepatectomy was combined with TOCE and in 8 PEI was combined with TOCE, while the rest were treated by TOCE alone. Tumor mass was reduced in 36% of those treated by TOCE (tumor volume reduced 24-75%). Alpha-feto protein (AFP) was reduced 25-90% in 20/32 of those with elevated AFP levels. Median survival for the 100 in the entire group was 19 months (10.9 months in those with conservative treatment). Median survival in the 57 in Okuda stage 1 and the 43 in stages 2 or 3 was 30.1 months and 10.9 months, respectively (p<0.0001). Of the 57 in stage 1, 16 underwent hepatectomy in addition to TOCE and 41 were treated only by TOCE (median survival 15 and 26 months, respectively, p not significant).

Comparing Okuda 1 patients treated by TOCE only with the natural history of the disease and historical controls (Okuda 1 patients treated conservatively in 1984) median survival was 26 and 10 months respectively (p<0.001). The side effects of TOCE were relatively mild. There was 1 fatality (3 days after treatment), and quality of life was maintained. Despite progress in the treatment of HCC by TOCE, PEI, and liver transplantation, long-term survival has remained unsatisfactory.

Diabetic Ketoacidosis during the Ramadan Fast 

I. Friedrich, Y. Levy

Dept. of Medicine A, HaEmek Medical Center, Afula, and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

We report a 15-year-old Muslim boy with insulin-dependent diabetes mellitus (IDDM) who presented with diabetic ketoacidosis (DKA) during the Muslim Ramadan month of day-time fasting. DKA apparently occurred due to omitting pre-lunch insulin combined with dehydration and overeating during the permitted sunset-to-sunrise meals.

It is well-known that fasting accelerates development of lipolysis and ketosis and increases glucagon levels. Thus, these pathophysiological aberrations related to fasting in ketosis-prone patients, in conjunction with fasting, endanger metabolic control in IDDM.

Malaria in Travelers Returning from Endemic Areas

Andre Matalon, Amos Yinnon

Kupat Cholim Klalit, Dan-Petah Tikva District, and Dept. of Family Medicine, Tel Aviv University; and Infectious Disease Unit, Shaare Zedek Hospital and Hebrew University-Hadassah Medical School, Jerusalem

2 cases of malaria in family practice are described in a 26- and a 50-year-old woman. Both probably could have been prevented had common chemoprophylactic drugs been taken. The risk of malaria is greater than the risk of possible side-effects of the drugs commonly used by travelers for prevention. Family physicians must be aware of the possibility of malaria in young people with fever, especially those who have travelled to equatorial areas and special attention should be given to encourage chemoprophylaxis.

Patient Satisfaction and Hospital Services Evaluation by Regular and Private Patients

Sara Carmel, Jonathan Halevy

Dept. of the Sociology of Health, Faculty of Health Sciences, Ben-Gurion University of

the Negev, Beer Sheba; Sha'are Zedek Medical Center and Hebrew University-Hadassah Medical School, Jerusalem

"Sharap" is a private medical service integrated within our public clinic and hospital services. Clients may choose their physician by paying a fee in addition to what their health insurance agency (Kupat Holim) pays for. All other hospital services are supplied to all patients alike. The main purpose of this study was to evaluate the extent to which this declared policy is maintained in practice.

During 5 months in 1997, 198 Sharap patients and 198 regular patients were interviewed in the the general surgery, cardiac surgery, ENT, cardiology, newborn and gynecology wards of this hospital. Both groups were similar in regard to cause of hospitalization, gender, age group (10-year age ranges), and length of hospitalization (at least 24 hours).

Similar levels of satisfaction with hospitalization in general and with the nursing service and with supportive services were found in both groups. However, Sharap patients were more satisfied with their physicians than regular patients (87% vs 74%, respectively). Similar results were also found using indirect measures of satisfaction. About 86% in both groups reported having achieved the goal of improvement in health. A high proportion of respondents from both groups (82% and 88%, respectively) could not distinguish between Sharap and regular patients in the ward. However, a greater proportion of regular patients (35% vs 21%) wanted more extensive explanations from their physicians regarding their treatment.

Sharap patients belonged to higher socio-economic classes than regular patients. Our evaluation indicates that although the Sharap service enables the affluent to choose their preferred physician, resulting in a different doctor-patient relationship, the service does not create a significant feeling of discrimination among hospitalized patients, and does not interfere with the high level of health services available to the public at large.