Development of Molecular Tests for Rapid Detection of Enteropathogens 

Miri Yavzori, Nir Uriel, Nurith Porat, Ron Dagan, Ruhama Ambar, Ofer Shpilberg, Dani Cohen

Army Health Branch Research Unit, Medical Corps, Israel Defense Forces; Pediatric Infectious Disease Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba; and Sackler Faculty of Medicine, Tel Aviv University

Amplification of specific DNA sequences by polymerase chain reaction (PCR), enables rapid, sensitive and direct, specific identification of pathogens at very low concentrations in clinical samples. Studies in recent years have reported identification of several enteropathogens directly from stool samples by PCR. The amplification process includes the use of primers complementary to the DNA sequences specific to the pathogen, thus relying on the pathogen's genotype, rather than its phenotype on which identification by the methods of classical microbiology were based.

We have developed PCR protocols for the differential identification of enteropathogens resembling the normal flora (enterotoxigenic E. coli (ETEC), E. coli O-157), Shigella spp, and the detection of enteropathogens that can not be grown on classic growth media (Norwalk virus). The amplification process is inhibited by several substrates present in fecal material (phenol, hemoglobin), limiting DNA extraction by phenol. The protocols we have developed for direct detection of Shigella spp and ETEC in stools circumvent inhibition of PCR by the use of a 4-hour pre-enrichment step in brain-heart infusion broth.

Rapid and accurate identification of enteropathogens is important for prompt and focused intervention to stop the chain of transmission in outbreaks of gastroenteritis in military and civilian populations.

Trends in Epidemiology of Hepatitis in the Israel Defense Forces 

Michael Gdalevich, David Gillis, Daniel Mimouni, Itamar Grotto, Ofer Shpilberg

Institute of Military Medicine, Medical Corps, Israel Defense Forces

During the 50's and 60's there were large scale epidemics of hepatitis A every 3-4 years in the Israel Defense Forces. During these epidemics the annual incidence exceeded 10/1000 soldiers at risk. There has been a highly significant decrease in rates during the past 30 years. The average annual incidence of clinically identified viral hepatitis A decreased from an average of 6/1000 during the 60's to 2.5/1000 during the 70's. The decrease coincided with the introduction in the 1970's of wide-scale post-exposure prophylaxis with immune serum globulin (ISG). The incidence was further significantly reduced to 0.5-1.0/1000 with the introduction of pre-exposure prophylaxis with ISG, starting in 1978 (p<0.001).

Other factors probably played a role in accelerating the decline in morbidity, such as improvement in personal hygiene and sanitation facilities, and in waste disposal and other aspects of military environmental health.

These improvements were probably more pronounced in the civilian sector, leading to decreased exposure of children to the virus and consequently a higher proportion of seronegatives at induction. Increase in the proportion of recruits without natural immunity to the virus poses greater risk, both in terms of personal morbidity as well as military operational ability. This risk, combined with problems of ISG use and availability, has propelled hepatitis A prevention policy towards the use of the new inactivated vaccines.

Decompression Sickness in Divers Treated at the Israel Naval Medical Institute 

A. Gil, A. Shupak, H. Lavon, Y. Adir

Israel Naval Medical Institute, Israel Defense Forces, Haifa

Clinical characteristics of 125 divers treated for decompression sickness (DCS) in the hyperbaric multiplace chambers of this Institute during 1992-1997 were analyzed retrospectively. In 62 (51%) the diagnosis was DCS Type I (joint pain or skin involvement) and in 60 (49%) DCS Type II (neurological, inner ear or pulmonary disease). Risk factors for the evolution of DCS were depth and duration of the dives involving accidents, violation of recommendations of the decompression tables, and repeated dives.

Results were available for 112 of the 125 patients. 54 of them (48%) recovered completely, and another 54 recovered partially; 4 did not respond to treatment. Inner ear DCS was less responsive to hyperbaric oxygen treatment (p=0.0001). There was significant improvement of neurological function in those with severe neurological injury (p=0.0001). Rapid diagnosis and transportation of divers with DCS to a hyperbaric chamber is of crucial importance.

Israel Naval Medical Institute: 20 Years of Applied Research, and Future Goals 

Ran Arieli, Avi Shupak

Israel Naval Medical Institute, Medical Corps, Israel Defense Forces

The Israel Naval Medical Institute (INMI) is unique as a research center located in a naval base and having close inter-relations with naval underwater units. It is ideal for applied research, and for mutual exchange of needs and of ideas and instructions.

Factors making this institute so suitable for applied research include: direct personal communication with combat divers, professional naval divers, submariners, civilian recreational divers and professional civilian divers, as well as naval vessel crews prone to seasickness; hyperbaric oxygen therapy is administered in cooperation with a large neighboring hospital.

Close spatial and personal relations with an academic institution (the Technion, with its Faculties of Medicine, Biology and Biophysics) provide a basis for cooperative research which expands research capabilities, and allows access to extensive expertise, instrumentation and equipment. Close ties with physicians who served at the INMI in the past also bring them into this research community.

During their specialization, physicians may spend up to 6 months working with us on a research project. Undergraduate, graduate and post-graduate students may complete their research at our institute with the agreement of their parent academic institutions.

Much of the research can be released to the international community. However, some is classified, serves only internal needs or is not of public interest. The number of published papers has stabilized since 1991 at about 16 a year.

Studies of gas exchange and oxygen toxicity originate mainly in the Hyperbaric Research Unit, research on motion sickness in the Motion Sickness and Human Performance Laboratory, and work on hyperbaric and diving medicine in the Clinical Section of the INMI.
 

Medical Support During The Sinai War Of Attrition (1968-1970): A 30-Year Perspective 

Z. Gimmon, J. Adler

Dept. of General Surgery, Hadassah-Hebrew University Medical Center, Ein Kerem, Jerusalem and Medical Section, Israteam, Lod

The War of Attrition between Israel and Egypt along the Suez Canal line lasted 23 months (9/1968-8/1970), during which the Israel Defense Forces (IDF) were mostly in fixed fortifications. A few of the important principles of field medical support, which became cornerstones of IDF procedure, were established during that war. These included use of armored vehicles for evacuation under artillery fire, as well as emergency treatment, physiological stabilization, and maintenance of the wounded until evacuation.

The latter objectives were achieved by stationing medical officers and paramedics within the fortifications, where they remained with the troops. A field surgical hospital was established in Refidim which had a trained surgical staff and a well-equipped emergency department. It included an operating theater and post-op recovery facilities for proper surgical care until evacuation to hospitals in the rear.

Tables showing the number of casualties throughout 1 year of the War of Attrition are presented. Better personal shielding by helmets and body shields decreased the number and severity of head and thoraco-abdominal injuries. The relative large number of those who died-of-wounds was due to the proximity of medical facilities, so that treatment could be administered within the fortifications. Otherwise, many more would have been included among the killed-in-action.

New Psychopharmacological Approaches in Mental Health as Applied by the Israel Defense Forces

Moshe Zvi Abramowitz, M. Shmushkevich, Avraham Weizman, Mordechai Mark

Mental Health Department, Medical Corps, Israel Defense Forces; Sackler Faculty of Medicine, Tel Aviv University; Jerusalem Mental Health Center; and Geha Psychiatric Hospital

In the past decade there have been far-reaching developments in psychopharmacology. Previously, only a few classes of medication were at the disposal of psychiatrists, as many had serious side effects that limited their use. Now our psychopharmacological armamentarium has grown considerably, allowing for greater choice of treatment in the military.

We review these developments, and discuss the special considerations to be taken into account when treating soldiers with psychiatric medication. We discuss suitable medication for ongoing outpatient treatment, as well as the standard list of medication currently used by units deployed in the field.

Advances in psychopharmacologic treatment should enable more soldiers to serve safely in the military with fewer restrictions on their duties.

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.

Man in a Hot Climate - Early Studies of the Institute of Military Physiology 

Ezra Sohar, Yair Shapiro, Yoram Epstein

Institute of Military Medicine, Medical Corps, Israel Defense Forces and Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer

In the 1950's many IDF soldiers were hospitalized for heat stroke - about 25% of whom died. Analyzing these cases revealed that commanders misinterpreted human ability to perform in the heat and ignored basic concepts of fluid and electrolyte balance and heat load.

In the early 1960's a series of studies was conducted with regard to soldiers' performance in the heat. The first study (1959), which later became a classic, was conducted during a 21-day march from Eilat to Metula, crossing all climatic zones of Israel. The study was followed by other investigations which approached the issues of voluntary dehydration, fluid consumption vs sweat loss, salt additives, and the effect of heat load on performance.

Based on these early studies, proper regulations were issued to field officers. Over the years, the lessons learned from these studies saved many lives. The number of cases of heat stroke and of other climate-related injuries was dramatically reduced, and performance was enhanced.

Prediction of Physiological Response from Mathematical Models 

Yoram Epstein, Yuval Heled, Daniel Moran, Yair Shapiro

Institute of Military Medicine, Medical Corps, Israel Defense Forces and Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer

The ability to predict the physiological responses of workers exposed to extreme environmental conditions, has been a challenge to environmental physiologists for more than 3 decades. Therefore, mathematical models have been developed to predict metabolic rate under various levels of work intensity and dynamic changes in body temperature and heart rate.

Based on the effect of exercise on the cardiovascular system, a model was developed to predict mean arterial blood pressure as a function of heart rate. Physiological strain could also be estimated on the basis of thermoregulatory and cardiovascular strains.

This paper summarizes knowledge accumulated during 25 years of studies in the field of mathematical modeling of physiological parameters. Besides analyzing the logic underlying each model, it explains the scientific approach in developing a model from its early concept to the model's application in the field.

Acetaminophen Toxicity in Children - A Therapeutic "Misadventure"

Sarit Shahroor, Yigal Shvil, Mely Ohali, Esther Granot

Dept. of Pediatrics, Hadassah University Hospital and Hebrew University Hadassah Medical School, Jerusalem; and Dept. of Pediatrics, Barzilai Medical Center, Ashkelon

Acetaminophen toxicity after repeated administration of amounts that only moderately exceed recommended doses, is being increasingly reported in alcoholic or fasting adults. Pediatric experience with this pattern of acetaminophen toxicity is sparse.

We present 2 children who developed severe hepatic damage, with renal insufficiency as well in 1, after 15-20 mg/kg of acetaminophen, given at 4-hour intervals for 3-4 days during an intercurrent febrile illness. When given in doses as low as 20 mg/kg at frequent intervals for a number of days, the drug puts children who are vomiting or have sharply reduced caloric intakes at increased risk for severe toxicity.

Increased caution and awareness of the toxic effects of acetaminophen are needed, and it should be dispensed with appropriate package-label warnings.

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.

Laparoscopic Approach in Treating Hepatic Cysts 

P. Schachter, V. Sorin, M. Shimonov, A. Rosen, A. Czerniak

Dept. of Surgery A, Wolfson Medical Center, Holon

Solitary and multiple hepatic cysts are now more commonly found because of advances in imaging techniques. Most hepatic cysts are asymptomatic, but when they do cause symptoms they require surgical intervention. The advent of laparoscopy and of laparoscopic ultrasonography allow comprehensive evaluation and treatment of the cysts.

12 patients with hepatic cysts were treated laparoscopically. 8 with single cysts underwent successful subtotal cyst resection without signs of recurrence (up to 20 years of follow-up). 4 with polycystic liver disease underwent sub-total resection of superficial cysts. Deep cysts were unroofed and drained under laparoscopic ultrasound guidance. In this group, 1 experienced recurrence of symptoms and required partial hepatectomy of the involved segment. In another, a connection between a deep cyst and bile ducts was demonstrated and cystojejunostomy was performed.

The laparoscopic approach in the management of patients with liver cysts is effective and safe, and we recommend it as the procedure of choice for single hepatic cysts. In polycystic liver disease the procedure is much less successful.

Tracheoesophageal Puncture after Total Laryngectomy

Roy Landsberg, Frida Korenbrot, Dov Ophir

Depts. of Otolaryngology and of Head and Neck Surgery, Meir Hospital, Kfar Saba and Sackler Faculty of Medicine, Tel Aviv University; and the Israel Cancer Association Voice Rehabilitation Program

Total laryngectomy due to malignant laryngeal tumors is followed by loss of speaking ability. Voice restoration in laryngectomized patients is the main target in their rehabilitation. Until the late 70's, esophageal speech was considered the most effective rehabilitation method. In 1980 Singer and Blom introduced a prosthesis for tracheoesophageal speech which has been gaining popularity. Tracheoesophageal puncture (TEP) can be performed either at the time of total laryngectomy, or later.

30 of our patients underwent TEP between 1991 and 1999, 15 at the time of total laryngectomy and 15 as a delayed secondary procedure. Mean follow-up was 36 months (range 6 months to 8 years) during which all regained speaking ability.

Over the long range, speech rehabilitation with the prosthesis was successful in 24 (80%). In only 1 in the primary TEP group did treatment fail, as the prosthesis had to be removed due to local recurrence of the tumor. Long range failure in 5/15 patients after secondary TEP stemmed from difficulties some patients had in handling the prosthesis and from psychological difficulties in adapting to the new speech device. Complications were mostly minor and occurred mainly in the secondary TEP group.

TEP performed at the time of total laryngectomy, or later as a secondary procedure, is effective for speech rehabilitation after laryngectomy.

Preflight Assessment by Hypoxic Inhalation Test in Cardio-Pulmonary Patients 

J. Lebzelter, G. Fink, E. Kleinman, I. Rosenberg, M.R. Kramer

Pulmonology Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva

Flying may expose passengers to hypoxic conditions, which may induce hypoxemia, particularly in those with chronic heart and/or lung disease. Onset of dyspnea, wheezing, chest pain, cyanosis and right heart failure can lead to urgent need for oxygen during flight. The hypoxia inhalation test (HIT) provides a safe and simple means of identifying those who may develop hypoxemia during flight.

We report our experience with 48 self-reporting patients who underwent HIT prior to pre-planned air travel. They inhaled for 15-minute periods a reduced oxygen concentration (F₁O₂ 15%) under normobaric conditions, during which O₂ saturation was monitored by pulse oximeter; electrocardiogram, blood pressure and symptoms were also monitored. O₂ saturation of 85% (PaO₂ 50 mm Hg) was considered a positive test. In the 8 cases (17%) with a positive test, 5 had chronic obstructive pulmonary disease and 3 had cardiovascular and/or combined heart-lung disease.

We calculated predicted O₂ partial pressure in altitude (PaO₂ ALT) and compared it to actual results in the 8 patients with a positive HIT. In 5, use of the predicted formula would have under-diagnosed the hypoxemia that developed during the HIT. Thus, the results of the HIT changed treatment strategy in these patients. We recommend that patients with positive tests use O₂ (2LPM or 4LPM) during flight.

HIT is practical and of potential benefit in the objective assessment of patients with various degrees of heart, lung or combined heart-lung disease. Clinicians should be aware of the relative risk of hypoxia during flight in such patients, and of the value of HIT in identifying them, leading to increase in its use.

Ethnicity and Emergency Department Visits in the Negev

Shahar Livnat, Eyal Almog, Gad Rabinowitch, Yoram Snir

Dept. of Emergency Medicine, Soroka University Medical Center and Dept. of Industrial Engineering and Management, Ben-Gurion University of the Negev, Beer Sheba

The population of the Negev consists mainly of Jews and Bedouin, who have very different life styles. Patients of both ethnic groups use our emergency department exclusively, providing a unique opportunity to study comparative patient habits.

In gathering and processing the information we used Data Mining technology, which allows search for unique patterns in large data bases. We examined demographic data on some 64,000 emergency department visits during 1997-8, mostly medical and surgical cases, but not trauma cases. Many more were by Bedouin than Jews, and between the ages of 25 and 44, more by women than men. There were changes in trends in comparison with an arrival survey conducted some 11 years before.