Prader-Willi Syndrome: Medical, Emotional and Cognitive Facets

Varda Gross-Tsur, Yael E. Landau

Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem

Prader-Willi syndrome, first described in 1956, is characterized by marked hypotonia, hyperphagia, severe obesity, short stature, hypogonadism, orthopedic problems, breathing- related sleep disorders, mild to moderate mental retardation and behavioral abnormalities. The incidence of this syndrome, an expression of a genetic imprinting error in chromosome 15, is 1:10,000-1:25,000.

We describe the medical, emotional and cognitive parameters of 34 patients in our multidisciplinary clinic for Prader-Willi syndrome. Their ages range from 5 months to 40 years and 20 are males. Excessive weight gain started at the age of 6 years, increasing to 170-370% of that predicted by height and age and short stature started after the age of 12. All males have hypogonadism; 6 patients have scoliosis. Breathing-related sleep disorders have occurred in 15.

Children above the age of 8 years underwent neuropsychological assessment: half (9/18) have borderline intelligence while a quarter have low-normal intelligence and the remainder mild to moderate mental retardation. Behavioral and social problems are common, and become more prominent during adolescence. ADHD was diagnosed in 10/18.

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.

Concomitant Coronary Artery Bypass Surgery and Pulmonary Lobectomy 

Amit Korach, Uzzi Izhar, Ehud Rudis, Amir Elami

Dept. of Cardiothoracic Surgery, Hadassah University Hospital, Jerusalem

Coronary artery disease amenable to percutaneous interventions or coronary artery bypass grafting, and resectable lung cancer are major causes of morbidity and mortality. We present our experience in the treatment of 3 patients (men aged 64 and 66 and a woman of 77) who each had significant coronary artery disease and a resectable lung tumor. They underwent combined coronary artery bypass grafting and pulmonary lobectomy.

We conclude from our experience and review of the literature that concomitant surgery in such cases is safe and effective, decreases suffering, and decreases the cost of 2 separate invasive procedures.

Mitral Valve Repair in Ischemic Cardiomyopathy with Severeleft Ventricular Dysfunction

Dani Bitran, Ofer Merin, Jeffrey Fisher, Nadiv Shapira, Marc W. Klutstein, Shuli Silberman

Depts. of Cardiothoracic Surgery, Anesthesiology and Cardiology, Shaare Zedek Medical Center, Jerusalem

Patients with ischemic mitral insufficiency and poor left ventricular function are high operative risks. We present 101 patients who had mitral valve repair in our department: 21 had severely reduced left ventricular function, 19 were in NYHA functional Class IV, and 2 in Class III. All had concomitant coronary artery bypass.

There was no early operative mortality, but there were 2 late deaths (9.6%). At follow-up (3-36 months) all valves were functioning normally, 9 patients (43%) were in NYHA functional Class I, and 4 (19%) in Class II.

Our experience shows that repair of ischemic mitral insufficiency in the presence of severe left ventricular dysfunction can be performed with good results, and is preferable to mitral valve replacement. Late follow-up showed significant symptomatic improvement.

Tacrolimus does not Accentuate Hepatic Damage due to Hypoperfusion 

Ron Ben Abraham, Ivgeni Isartal, Richard Nakache, Vallery Rudick, Daniel Ogorek, Gideon Paret, Avi Weinbroum

Dept. of Anesthesiology and Critical Care Medicine, Organ Transplantation and Postoperative Care Units, Tel Aviv-Sourasky Medical Center; and Pediatric Intensive Care Units, Sheba Medical Center, Tel Hashomer; and Sackler Faculty of Medicine, Tel Aviv University

Deterioration of hepatic function following liver transplantation is a known complication, sometimes attributed to the use of cyclosporin A. Reaction to tacrolimus (Prograf), a relatively new and effective immunosuppressant drug, is thought to result in a much lower grade of organ dysfunction, especially in the transplanted liver.

Using the ex-vivo rat model of isolated perfused liver, we evaluated hepatocellular damage and oxygen extraction when tacrolimus was administered following liver hypoperfusion. Tacrolimus did not worsen hepatic dysfunction caused by the hypoperfusion. Therefore using tacrolimus in the perioperative period might be safer than cyclosporin A, which tends to worsen hepatic damage in the presence of hypoperfusion.

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.

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.

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.

Placenta Accreta with Placenta Previa after Previouscesarean Sections 

Eylon Lachman, Alexander Mali, Gabriel Gino, Michael Burstein, Michael Stark

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

The increased rate of cesarean sections in recent decades has brought with it an increase in the frequency of placenta accreta. There are direct correlations between previous cesarean deliveries and also maternal age, with the risk of placenta accreta. There is also a direct correlation between placenta accreta and placenta previa.

The risk of placenta accreta in women who have had placenta previa is 2% for those younger than 35 years and with no history of uterine surgery. The risk increases to 39% for those over 35 who have had 2 or more cesarean sections.

We present 3 cases of placenta accreta admitted in 15 months, all of whom had a history of cesarean sections. The frequency of placenta accreta in our hospital is 1:1,579 deliveries, in line with the 1:1,420 in the literature. We consider hysterectomy the treatment of choice for this serious complication. When performing a cesarean in cases of placenta previa with a history of cesarean sections, the possibility of placenta accreta should be considered.

Etoposide and Cisplatin for Non-Small Cell Lung Cancer 

David B. Geffen, Sofia Man, Yoram Cohen*

Dept. of Oncology, Soroka-University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Etoposide and cisplatin (EP) has been the standard therapy for non-small cell lung cancer (NSCLC) at many cancer centers for over a decade. We analyzed our experience with EP in NSCLC to provide a baseline for comparison with new drugs. From 1986 through 1994, 46 of our patients with NSCLC received EP as first-line chemotherapy. Radiation therapy was administered to 25 of them, including 20 who received it immediately before or concomitantly with chemotherapy. Toxicity was mild and included only 1 episode of neutropenic fever and 1 case of reversible renal failure.

Overall response was 22%. In 3, response was complete (pathologically documented in 2 of them) and in 7 partial. Median survival in locally advanced (stage III) and metastatic disease (stage IV and recurrent) were 12 months and 7 months, respectively. 2 patients are alive and free of disease more than 6 years after diagnosis.

Our results are consistent with other published studies of EP in NSCLC. EP provides modest benefit in locally advanced NSCLC, with minimal toxicity.

Jules E. Harris Chair in Oncology.

Alopecia Due to Seroxat 

Leonid Umansky, Abraham Dorevitch, Avner Sella

Psychiatry Chronic Dept., Eitanim Mental Health Center, Jerusalem

There are 2 stages of alopecia, anagen and telogen effluvium, both of which may be associated with medication- related alopecia. We describe massive hair loss in a 51-year-old woman during treatment with Seroxat (paroxetine), which remitted after it was discontinued. Pathological mechanisms of drug-associated alopecia are complex and have yet to be fully elucidated.