Hemophagocytic Syndrome

I. Morag, M. Goldman, T. Bistrizer, C. Kaplinsky

Pediatric Division, Assaf Harofeh Medical Center, Zerifin and Pediatric Hematology-Oncology Dept., Chaim Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

Hemophagocytic syndrome is a rare, fulminant disease characterized by generalized histiocytic proliferation associated with phagocytosis of erythrocytes, platelets, and to a lesser extent, of white blood cells. We report a 2-year-old boy admitted with high fever and irritability, with a rash, marked hepatomegaly and generalized lymphadenopathy. Liver function tests were abnormal and there was thrombocytopenia and hyperlipidemia. Bone marrow aspiration revealed hemophagocytosis. Despite intensive treatment with steroids, intravenous immunoglobulin and cytotoxic drugs, he died within 10 weeks.

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.

Apomorphine for "Off-Periods" in Parkinson's Disease

J. Zoldan, D. Merims, A. Kuritzky, I. Ziv, E. Melamed

Dept. of Neurology, Rabin Medical Center, Beilinson Campus, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University

After 3-5 years of continuous use of 1-dopa preparations for Parkinson's disease, 25%-50% of patients develop side-effects such as the "on-off" phenomenon and involuntary movements that markedly impair function. One cause of these manifestations is evidently a disturbance in the absorption of 1-dopa.

We attempted to avoid this problem by using subcutaneous injections. Apomorphine is a rapid-acting dopamine agonist which causes a return from "off" to "on" within minutes.

We present the results of a trial of subcutaneous injections of apomorphine in 22 Parkinsonian patients (12 males, 10 females) with severe motor fluctuations. During 5 days prior to the apomorphine all received Motilium (domperidone, 60 mg/d) to prevent nausea and vomiting. All were hospitalized initially to determine optimal dosage and to teach them the technique of self-injection.

2 to 4 mg of apomorphine were injected 1 to 3 times daily for 2 to 12 months. In 17 patients (80%) "off" periods were reduced without significant side-effects. Apomorphine seems to be effective, tolerable treatment for shortening 1-dopa induced "off" periods.

Injuries Due to Falls in Urban Buses: 100 Consecutive Cases 

Ron Bachar, David Aladgem, Jacky Sarov, Patrick Sorkine, Oded Szold, Pinchas Halpern

Dept. of Emergency Medicine and Critical Care Unit, Tel Aviv-Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University

We reviewed the charts of 100 consecutive emergency department (ED) cases of injuries in public buses (not due to actual traffic accidents) seen during 7 months in 1995. There were 29 males and 71 females with a mean age of 55.6-21.4 years, median 60, and range 13-91. 92 were discharged home directly from the ED. 3 were admitted to general surgical wards, and 1 each to the orthopedic, medical and neurosurgical wards, while 2 soldiers were sent for observation to a military clinic.

There were 28 spinal column, 27 head and 25 chest injuries; 1 patient died. There were no significant differences in admissions during the months of the year. 58% of injuries occurred during normal working hours, with a peak incidence at about 1000 hrs. The most common cause was falling while standing, due to sudden acceleration/deceleration or sharp turns.

There are 1900 buses in Tel Aviv which carry 1.1 million passengers daily and most of which are capable of significant acceleration. A high proportion of passengers travel standing, and elderly passengers are more liable to fall when the bus accelerates, decelerates or turns. We calculate a potential national yearly bus injury toll from falls of more than 1000, which often result in significant morbidity and even mortality. A national survey is now being planned.

Prevalence of Medical Complaints in the Community-Dwelling Elderly

J. Gindin, M. Geitzn, M. Dushenat, H. Siboni, D. Goldstein, Z. Shapira, N. Konstantin, A. Wurm, A. Goldsmid, E. Hay-Am

Geriatric Institute of Education and Research, Kaplan Medical Center, Rehovot; Pharmacology Dept., Kupat Holim Klalit, Tel Aviv and Central District; and Kupat Holim Klalit, Rishon LeZion

We assessed the prevalence of self-reported medical complaints among the community-dwelling elderly receiving regular medication, and determined associations between health and sociodemographic variables, and the prevalence of complaints.

The study included 170 patients, 60-90 years of age, living at home. Participants were recruited from the 3 main primary care clinics in Rishon LeZion. All were receiving chronic medication and were followed-up utilizing a long-term medication card. Data were gathered in interviews held in patients' homes using a structured questionnaire which included sociodemographics, diseases and medication, mental state assessment by Katzman's score, and a list of 15 medical complaints common among the aged. Relations to age, gender, education, living arrangements, number of diseases and number of medications per patient were determined.

Mean age of participants was 73.2±6.0 years and they suffered an average of 4.07±2.16 diseases and took 5.10±2.83 types of drugs. The most prevalent complaints were: weakness and fatigue (65.0%), agitation and restlessness (56.4%), dry mouth (45.6%), constipation (43.6%) and dizziness (43.2%). The number of diseases, gender, education and age had the strongest associations with the prevalence of specific complaints, as well as their total number. The association between number of medications and mean number of complaints was of borderline significance.

Severe Heat Stroke in an Intensive Care Unit

Amir Halkin, Dina Lev, Oded Szold, Philip Bidermann, Sarah Bulocnic, Pinchas Halpern, Patrick Sorkine

Depts. of Medicine and Surgery, and Intensive Care Unit, Tel Aviv Medical Center

During the August 1998 heat wave in Tel Aviv we admitted many patients for acute heat-related illness; 6 had severe heat stroke and were admitted in critical condition. We describe their clinical courses during the first 5 days of hospitalization, including response to treatment and implications for future management of this disorder.

The mean APACHE II score of the 6 was 30±3.5 and mean Glasgow Coma Scale rating 3.5±0.5; they were in hypovolemic shock and respiratory failure, necessitating mechanical ventilation. Despite early effective therapy (core temperature in all was reduced to less than 398C in less than 1 hour), there was 1 death (mortality 15%) and 4 required further intensive care for life-threatening multiple organ failure.

During severe heat waves a significant number of referrals for acute heat-related illness must be anticipated, possibly overwhelming admission capacity of regional intensive-care units. Severe heat stroke complicated by multi-organ failure is not necessarily related to prior physical activity. Although important in determining prognosis, early treatment does not prevent severe complications. Mechanisms regulating body heat may remain disturbed for days following early treatment and apparent stabilization, mandating continued hospitalization.

Laparoscopic Donor Nephrectomy: Initial Experience

Amir Szold, Joseph M. Klausner, Richard Nakache

Advanced Endoscopic Surgery Unit, Transplantation Unit and Depts. of Surgery B-C, Tel Aviv-Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University

We present our initial experience in laparoscopic nephrectomy. 6 patients were operated for a kidney donation and 2 for treatment of a benign disease. All procedures were completed successfully, with no conversion to laparotomy or intra-operative complications. Mean operating time was 210 minutes, and in the donor kidneys the mean warm-ischemic time was 165 seconds. There were 3 postoperative complications, and mean hospitalization was 3.5 days. The transplanted kidneys are all functioning.

From our initial experience, laparoscopic nephrectomy appears to be both feasible and safe. Its implementation requires a combined team with experience in donor surgery and advanced laparoscopic skills. The procedure may increase the availability of living donor kidneys, due to the smaller impact on the donor compared to conventional donor nephrectomy.

Laparoscopy for Common Bile Duct Stones

Ibrahim Matter, Moshe Wald, Shmuel Eldar

Depts. of Surgery and Urology, B'nai-Zion Medical Center, Haifa

We performed 75 laparoscopic cholecystectomies during July and September 1996. In 3 men and 4 women, aged 32-87 years, there was obstructive jaundice caused by choledocholithiasis. During laparoscopy in the jaundiced patients, calculi were identified by cholangioscopy and intra-operative cholangiography. They were washed into the duodenum (confirmed cholangiographically) after intravenous glucagon injections and dilation of the papilla of Vater.

Serum bilirubin and liver enzyme levels returned to normal within a few days. There was no operative or postoperative morbidity, nor any biliary-related systemic complications. Average postoperative hospitalization was 3 days.

Irradiation Injury of the Salivary Glands

R. M. Nagler

Dept. of Oral and Maxillofacial Surgery and Oral Biochemistry Laboratory, Rambam Medical Center and Technion Faculty of Medicine, Haifa

Ionizing irradiation of the salivary glands often leads to severe histological and functional alterations. Such exposure usually occurs during radiotherapy in patients with head and neck malignancy. The consequent xerostomia, often life-long, may result from even relatively low dosage irradiation, and causes a great deal of suffering. We suggest a radiobiological mechanism for this phenomenon which has been studied extensively since first described in 1911. The suggested injurious role of redox active transition metal ions and highly destructive free radicals is discussed in relation to the ultimate radiosensitive cellular target, DNA.

Reactive Increase in Blood Pressure on Immobilization, but not Hypertension, Prevents Pressure Ulcers

Vladimir Shats, Silvio Kozacov

Geriatric Dept., Rebecca Sieff Hospital, Safed

Of 135 geriatric patients immobilized for at least 2 days, 37 (27.4%) had pressure ulcers (PU). Those without PU were the control comparison group. Gender, length of immobilization, number of blood pressure determinations and proportion with hypertension were similar in those with and without PU. Those with PU were slightly older than those in the comparison group: 75.5±8.8 and 74.7±9.6 years, respectively (p>0.05).

Of 66 patients with acute ischemic stroke, reactive increase of systolic or diastolic blood pressure to 140/90 mm Hg or above following immobilization, was seen in 60.6% and 22.7% of patients, respectively, and there were PU in 12.1%. Of 17 with recurrent ischemic stroke, corresponding figures were: 41.2%, 23.5% (p>0.05), and 47.1% (p<0.01). In 7 patients with previous ischemic stroke corresponding figures were: 14.3% and 0% (p<0.01) and 100% (p<0.001). In 36 operated for fracture of the femur, corresponding figures were: 50%, 11.1% (p>0.05), and 27.8% (p>0.05). For 9 patients with severe infections, sepsis or pneumonia, the corresponding figures were: 22.2% and 0.0% (p>0.05), and 44.4% (p<0.04).

The proportion of patients with reactive increase in systolic blood pressure on immobilization was lower in the PU group than in the controls, 27% vs 59.2%, (p<0.001). The corresponding figures for reactive increase in diastolic blood pressure were similar, 8.1% and 20.4%, respectively (p>0.05).

The mean systolic blood pressure on immobilization was higher in the control than in the PU group, 145.4±21.7 and 130.8±14.9 mm Hg, respectively (p<0.001). The corresponding figures for the mean diastolic blood pressure were similar, 81.2±10.5 and 75.7±8.9 mm Hg, respectively (p<0.01). An increase in systolic blood pressure on immobilization reduced the risk of developing PU (p<0.05).

There was no significant statistical relation between diagnosis of hypertension and proportion of patients with PU (p>0.05). Of 67 patients with hypertension, in 23.9% and 74.6% of them there was no increase in systolic or diastolic blood pressure, respectively. Statistical difference between lack of diastolic or systolic response was very significant (p<0.001).

Reactive increase of blood pressure, but not hypertension, predicts reduced risk of PU on immobilization in the hospitalized elderly. Diminished reactive increase of blood pressure in response to stress of any kind may be a criterion of frailty and reduced physiological reserves. Efforts to reduce elevated blood pressure when a patient is immobilized appear irrational.

Circadian Fluctuations in Efficacy of Streptokinase Thrombolysis

E. Goldhammer, L.Kharash, E.G. Abinader

Cardiology Dept., Bnei-Zion Medical Center and Technion Faculty of Medicine, Haifa

This study was designed to assess possible diurnal fluctuations in the efficacy of thrombolysis with streptokinase. 156 consecutive patients treated with streptokinase during the period 1.1.95-1.7.96 were studied retrospectively. Success or failure of thrombolysis was determined according to the accepted clinical and angiographic criteria starting at midnight, 12 times at 2-hour intervals, then 8 times at 3-hour intervals, and then 6 times at 4-hour intervals. A definite peak for successful thrombolysis was found in the late afternoon and early evening hours. Between 16:00-20:00 PM, in 30.23% successful thrombolysis were observed, compared to 6.98% between 20:00-24:00 PM (p<0.05) and in 10.53% between 00.00-04:00 AM (p<0.05).

Multiple regression analysis showed that the independent factor with the greatest impact on successful reperfusion was the actual time until thrombolysis (p=0.037); then came the interval from pain onset to streptokinase administration (p=0.020), while age and gender had much lesser impacts (p=0.328 and 0.215, respectively), and individual risk factors even less.

These findings may have several clinical implications: dose adjustment for the time of day may be required, with larger doses needed during morning hours, or preference for primary coronary angioplasty to avoid increase in bleeding complications due to higher doses of thrombolytic agents.

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. 

Operative Laparoscopy in Pregnancy

Eylon Lachman, Abraham Schienfeld, R. Boldes, Samuel Levin, Michael Burstein, Michael Stark

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

The development of laparoscopic surgery in gynecology and general surgery has greatly advanced over the past decade, and recently has been successfully performed in pregnancy. In the English literature we found that of the 518 cases reported (mean age 32 years) the most common was for cholecystectomy (45%), followed by operations on the adnexae (34%), appendectomy (15%) and others (6%). To these we add 3 cases of cholecystectomy and 1 of an adnexal tumor. Of all the reported cases, 33% were performed in the 1st trimester, 56% in the 2nd and 11% in the 3rd.

This review demonstrates a definite trend to laparoscopy in pregnancy. It appears to be safe when performed by experienced surgeons, but further studies addressing safety of laparoscopic surgery during pregnancy are needed to reach definitive conclusions.

Legionellosis in Israel

Ida Boldur, Silviu Hoffmann, Regina Kazak, Batzion Benjamin

Institute of Microbiology, Assaf HaRofeh Medical Center, Zrifin and Dept. of Life Sciences, Bar-Ilan University, Ramat Gan

Infection with Legionella remains an important cause of disease and death. We analyzed our laboratory data from 1993 through 1997, augmented by our 20 years of experience. The incidence of Legionella as a cause of pneumonia varied in our study from 5%-9%, with a slight increase during the winter. Isolation of these microorganisms from different water sources was higher during the summer and ranged from 7%-70%.

Special laboratory tests are necessary to diagnose the disease and monitor these bacteria in water samples. The serologic method - indirect immunofluorescent assay -- for 41 serogroups of Legionella was the main diagnostic method used. Legionella sg. 1 was the most frequent cause of the disease, with an incidence of 52% in 1993, decreasing to 15% in 1997. An increase in the incidence of seropositivity to "other Legionellae" is characteristic for our country.

No correlation was found between the incidence of isolation of a specific strain and exposure. However, it is well known that the disease is overtreated but underdiagnosed, which requires reversal. Larger studies of Legionella colonization in water supplies and in air are needed in order to establish the risk of infection. Water sources are presently under-studied, as are respiratory devices in hospitals, or they are not studied at all in Israel, such as in mist machines in supermarkets, in dental clinics, and in ships and airplanes.

Alcoholic Delirium: Warning Signs and Diagnosis

Eliezer Witztum, Izhak Z. Ben-Zion, Vladimir Lerner

Community Mental Health Center; and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Lately an increasing number of physicians are asked to diagnose and treat physical and mental disorders caused by alcohol abuse, a phenomena which had been quite rare in Israel until recently.

Early diagnosis and efficient treatment are essential for the management of alcohol-dependent patients. Primary care physicians and hospital personnel should be more alert to the growing numbers of alcohol abusers and to their appropriate diagnosis and treatment. This article describes and summarizes the symptoms of alcohol withdrawal in general, and alcoholic delirium in particular. Problems in diagnosis and treatment are illustrated by typical cases, pointing out early clinical warning signs and suggesting some treatment guidelines.