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.

Breast Cancer after Mantle Field Irradiation for Hodgkin's Disease 

A. Katz, B. Brenner, A. Sulkes, H. Luria, G. Marshak, E. Fenig

Oncology Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University

Effective use of modern therapeutic modalities results in the cure of 75%-80% of Hodgkin's disease patients, regardless of stage. The major threat to continued survival is, therefore, not recurrent disease but development of second malignancies. Recent reports have firmly established the increased risk of breast cancer developing in women treated with mantle field irradiation.

We describe 3 women who developed breast carcinoma following mantle field irradiation for Hodgkin's disease. Their clinical course was consistent with that reported in larger series. They were relatively young when irradiated and there was a long interval between radiation therapy and the diagnosis of breast cancer.

Review of the literature shows that there may be a role for prophylactic mastectomy after irradiation for Hodkgin's disease.

Color Doppler Imaging of Central Retinal Artery in Retinopathy of Prematurity

Alon Harris, Hanna J. Garzozi, Mira Harris-Izhak, Nir Shoham, Daniel R. Holland

Depts. of Ophthalmology, Indiana University School of Medicine, Indianapolis and of HaEmek Medical Center, Afula; and Eye Health Northwest, Portland, Oregon

Color Doppler imaging (CDI) is a noninvasive technique, combining 2-dimensional brightness-modulated (B-mode) ultrasound evaluation of eye and orbital structures, with simultaneous color-coded Doppler imaging of orbital blood flow. It has been used to characterize various ophthalmic disorders in adults. Currently there is no data describing orbital blood flow parameters in either normal children or in those with ophthalmic disease, such as the retinopathy of prematurity (ROP).

We evaluated blood flow in the central retinal artery of preterm infants undergoing examination for ROP. We also investigated whether useful readings could be obtained on a consistent basis, and the reproducibility of differences in central retinal artery blood flow between subjects with and without ROP (including the influence of "plus" disease).

We obtained hemodynamic readings in 43 of 46 eyes of preterm infants. 13 eyes had no signs of ROP; 18 had ROP (at least stage 1) without "plus" disease, and 12 had ROP with "plus" disease. There were no statistically significant differences in systolic blood flow velocity within the 3 groups. However the average velocity was slower in the "plus" disease group, correlating with the clinical finding of dilated and tortuous blood vessels which characterize the posterior retina of ROP eyes with "plus" disease.

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.

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.

Non-Penetrating Deep Sclerectomy without Collagen Implantfor Glaucoma

Ben Zion Silverstone, Isaac Aizenman, Carmit Landau, Yaacov Rozenman

Ophthalmology Dept., Shaare Zedek Medical Center, Jerusalem

Deep sclerectomy (DS) can be used in glaucoma with increased intraocular pressure when medical treatment fails. It involves removing part of the ocular drainage apparatus. Resistance to intraocular fluid drainage is decreased, improving drainage and decreasing intraocular pressure. By avoiding anterior chamber penetration, DS diminishes frequency of the complications of filtering surgery.

24 eyes of 23 patients underwent DS for primary or secondary open angle glaucoma with elevated intraocular pressure not controlled medically. It included preparation of a 4.0 x 4.0 mm limbal-based external scleral flap, dissecting and removing most of an internal scleral flap (leaving it 1 mm smaller than the external flap), unroofing Schlemm's canal and removing fine endothelial tissue lining its inner walls. The external scleral flap was then repositioned and sutured. Collagen implants were not used. In some cases DS was combined with extracapsular cataract extraction and intra-ocular lens implantation.

Mean intraocular pressure decreased from 24.8‏3.9 mmHg initially to 12.8‏4.4 mmHg 6 months after operation (p<0.0001). There was no difference in postoperative intra-ocular pressure between DS as a single procedure or as part of a combined operation. Comations were mild and of short duration.

If long-term follow-up shows that lowered intraocular pressures are maintained, DS should be a surgical option in earlier stages of glaucoma.

Relationship Between Preterm Birth and Exertion During Pregnancy

S. Gazit-Nissim, E. Sheiner, M. Mazor, I. Shoham-Vardi

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

The relationship between physical activity at home and at work during pregnancy and preterm birth was studied. Using a case-control design, 99 women who delivered preterm were compared with 189 women who had term deliveries. The risk of preterm birth was tested in relation to characteristics of work in and outside the home. All women were interviewed post-partum before discharge.

There were no statistically significant differences between the groups in relation to sociodemographic and obstetrical factors, but level of education was significantly lower in the study group versus the control group (p=0.001).

Women who delivered preterm had devoted less time 3 months prior to delivery to household chores (mean of 3.7 hours vs. 4.8 hours in the control group, p=0.002). They also had spent less time walking around the home than the controls (1.2 vs. 1.5 hours, p=0.02). There were no differences between the groups in relation to physical activity outside the home, not during working hours, nor in duration of work. Significantly fewer women who delivered preterm were active in sports (odds ratio 0.22; 95% confidence interval 0.50-0.65; p=0.002).

A low level of education was significantly related to the risk of preterm birth, which may have resulted from lesser compliance with their physician's recommendations. It appears that in women not used to significant physical activity but who had access to adequate prenatal care, physical effort during pregnancy was not related to a higher risk of preterm birth.

High Dose Endobronchial Brachy - Therapy for Malignant Airway Obstruction

Alex Yarmolovsky, Alan Katz, Eyal Fenig, G. Fink, Daniel Bendayan, Aaron Sulkes, Mordechai R. Kramer

Institutes of Pulmonology and Oncology, Rabin Medical Center, Beilinson Campus, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University

Brachytherapy is especially suitable for palliative treatment of endobronchial tumors adjacent to internal organs that might be damaged by intensive external beam radiation, but are easily accessed with a flexible bronchoscope. This treatment is mostly palliative.

30 patients underwent such palliative high-dose endobronchial brachytherapy to alleviate malignant airway obstruction. With the aid of a flexible fiberoptic bronchoscope an endobronchial catheter was inserted adjacent to the tumor and treatment delivered using a 192Ir remote afterloader for 5-10 min, in 2 or 3 sessions.

There was symptomatic improvement in 26 (86%) and objective improvement in 27 (90%). 1 patient died of hemoptysis.

Botulin Toxin for Spasticity in Spinal Cord Damage

Ofer Keren, Flabia Shinberg, Amiram Catz, Neer Giladi

Loewenstein Rehabilitation Hospital, Ra'anana; Movement Disorder Unit, Tel Aviv Medical Center; and Sackler Faculty of Medicine, Tel Aviv University

Therapeutic injection of botulin toxin is well-recognized for reducing tonus in local dystonia. However, its efficacy in reducing spasticity in spinal cord injuries is still unproven. 4 men and 1 woman (mean age 39 years, range 20-56) with spinal cord injury and debilitating spasticity, and no response to standard treatment for spasticity received injections of botulin, 200-300 U, into 4-8 points in their legs to block muscle-nerve synapses.

In all 5 tonus was reduced in the area of the block, while in some it was also reduced in more distal muscles. In 1 there was reduced tonus in both the injected and contralateral leg. The therapeutic effect on tonus persisted for 3 months. In spite of objective improvement in tonus in all 5, only 3 felt subjective improvement, but in none was there improvement on standard functional scaling.

We found injection of botulin toxin effective in reducing tonus in the spinal cord-injured, and to some extent in improving subjective feeling of well-being in some of them. Obective measurement might show functional improvement after larger doses of toxin injected into more muscles. This might be necessary because the muscle mass of the legs is large and the intensity of involuntary contraction is especially high in these patients.

Identifying the Elderly at Risk for Falling 

D. Galinsky, V. Fried, A. Biderman, J. Cwikel, Y. Ben Moshe

Geriatric Dept., Soroka University Hospital and Depts. of Family Medicine and of Social Work, Faculty of Health Sciences, Ben-Gurion University of the Negev; and ESHEL, Beer Sheba

Falling is one of the main problems affecting the health of the elderly. A community project was carried out to detect elderly people at high risk for falls. One of its aims was also to develop tools allowing primary care professionals to detect the elderly at risk for falling. Such a screening test in the community-dwelling elderly (EFST) and a protocol for diagnosis and treatment of the elderly at risk for falls is presented.

Type 2 Diabetes among Adolescents in Israel 

Orit Pinhas-Hamiel, Ilana Koren, Pnina Vardi

Maccabi Juvenile Diabetes Center, Ramat Hasharon and Lin Diabetes Center, Haifa

Type 2 diabetes has been considered rare in children and adolescents. Recently, increase in the incidence of type 2 diabetes has been reported among adolescents in various parts of the world. We report the occurrence of type 2 diabetes among adolescents in Israel.

A boy of 14 and girls of 16.5 and 17 were pubertal and extremely obese, with a body mass index (BMI) between 39-47 kg/m². Acanthosis nigricans, elevated diastolic blood pressure, and hirsutism with menstrual disorders, were associated with insulin resistance, and should raise suspicion of type 2 diabetes. Significant obesity and strong family histories of type 2 diabetes appeared to be important risk factors. Since type 2 leads to long-term morbidity and mortality, its early identification and appropriate treatment are crucial.

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.

Spontaneous Bilateral Ectopic Pregnancy 

David Rabinerson, B. Kaplan, Zion Ben Rafael, Arie Dekel

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

Bilateral, spontaneous ectopic pregnancy is rare (1 in 125-1580 ectopic pregnancies). We describe a 30-year-old, unmarried woman with no predisposing factors for ectopic pregnancy who presented in hypovolemic shock, in the 7th week of gestation, complaining of abdominal pain. On immediate laparoscopy there were found blood and clots in the abdominal cavity, a left ampullar pregnancy (5 cm in diameter), and there was active bleeding from the fimbria of the right tube. Bilateral salpingectomy was performed and she received 3 units of packed red cells. She was discharged in good condition 3 days later. The pathologic diagnosis was pregnancy in each tube. This case emphasizes the need for thorough sonographic and laparoscopic observation in order not to miss the presence of bilateral ectopic pregnancy.

Model Internet Course for Physicians 

Arthur Leibovitz, Silvia Balan, Beni Habot

Geriatric Medical Center, Shmuel Harofeh Hospital, Be'er Ya'akov,  (Affiliated with Sackler Faculty of Medicine, Tel Aviv University)

The Internet is efficient in coping with the ever-increasing volume of medical knowledge. This and other functions have lead to its integration into daily medical practice. It is therefore imperative to disseminate its use among physicians, as some, unfamiliar with the personal computer (PC), may be reluctant to learn to use it. We therefore developed a course for training physicians in the basics of Internet use, consisting of 6 sessions of 2 hours each. It includes training in PC operation as well as in the main Internet functions. The topics are medicine-oriented, including Medline search, general info search, exploring medical sites and reading medical journals on-line.

41 physicians (8 groups of 4-6 each) with various specialties attended, of whom 38 completed a feedback questionnaire 4 weeks later. 79% reported using the Internet either at home or at their working place. The function used mostly was Medline Search (68%). Although 83% had not been familiar with the PC before, 96% stated that the course was clear and understandable and 99% expressed satisfaction with the quality of the teaching. Based on these results we recommend this course as a model for teaching physicians the use of the Internet.
 

Cervical Ectopic Pregnancy

Eyal Sheiner, Ilana Yanai, David Yohai, Miriam Katz

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

Cervical pregnancy is a rare but serious complication. The most frequent presenting symptom is vaginal bleeding, and is thus common in inevitable abortion. Examination reveals a dilated cervix containing products of conception derived from the emptied uterine cavity. The pathologic criteria are cervical glands opposite the placental site, attachment to and actual invasion of the cervix by the placenta, a portion of the placenta below the posterior reflection, and no fetal parts in the corpus uteri. Treatment ranges from hysterectomy to treatment with chemical agents, mostly methotrexate. We present a case of ectopic, cervical pregnancy with exaggerated placental site in the cervix.