Psychogenic Polydipsia Leading to Water Intoxication

L. Umansky, A. Sella

Psychiatry Dept., Eitanim Mental Health Center (Affiliated with the Hebrew University-Hadassah Medical School, Jerusalem)

Psychogenic polydipsia and its frequent complication, water intoxication, are well-known to psychologists. There are biochemical and psychiatric theories of psychogenic polydipsia which often correlate with each other.

A 48-year-old man with chronic paranoid schizophrenia developed symptoms of psychogenic polydipsia. This provoked disturbances in electrolyte balance, resulting in a rapid decrease in serum sodium concentration and eventual death. There is a paucity of information and little awareness of this problem in the professional literature.

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.

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.

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.

Combination Chemotherapy in Metastatic Urothelial Cancer

A. Sella, D. Flex, D. Gafni, O. Rabinovitz, A. Sulkes, J. Baniel

Genitourinary Medical Oncology Unit, Depts. of Oncology and Urology, Rabin Medical Center, Beilinson Campus, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv

The treatment of metastatic urothelial cancer is based on the combination of cisplatin, methotrexate, vinblastine and adriamycin (M-VAC). From November 1994 to May 1997 we treated 25 patients (51 men, 3 women, aged 50-77) with M-VAC. The tumor originated from the urinary bladder in 14 (56%) and the upper urinary tract in 11 (44%). Disease sites included: primary - 5 (25%), lymph nodes - 17 (68%), lungs - 10 (40%), bones - 8 (32%), pelvic mass and liver each - 4 (16%), with an overall median of 2 (1-5) sites per patient.

9 patients (38%) had complete responses and 8 (32%) had partial responses, for an overall response rate of 68% (95% CI 48.5%-85%). The median duration of response was 15.3 (1.6-29.6+) months. Median survival of responders was 19.1 (4.8-35.7+) months compared to 6.2 (0.7-11.2) for the non-responders (p<0.05). 13 (52%) of patients are alive, of whom 8 (32%) are free of disease and 5 with a single metastatic site on presentation at follow-up.

In the 118 treatment cycles we observed grade III-IV toxicity: myelosuppression 53 (45%), thrombocytopenia 4 (3%), stomatitis 8 (6.7%), diarrhea 3 (2.5%). There were 22 infectious episodes and 1 patient died of sepsis.

We achieved a high response rate with the combination M-VAC. However, only a third had long-term disease-free states and treatment was associated with excessive toxicity. Thera-peutic approaches with new agents are required to improve the response rate and toxicity.

Diarrheal Disease among Care-Givers at Children's Day- Care Centers 

S. Koton, D. Cohen, M.S. Green

Israel Center for Disease Control, Ministry of Health and Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer; Medical Corps, Israel Defense Forces; Dept. of Epidemiology and Preventive Medicine; Sakler Faculty of Medicine, Tel Aviv University

Diarrheal disease tends to spread from infected children to their families. Due to the increased risk of exposure, children's caregivers in day-care centers may have a higher incidence of diarrhea, particularly when caring for very young children. We therefore examined the incidence of diarrhea and antibodies to Shigella among caregivers in day-care centers, according to age groups of children in their care (<18, 18-34, and >35 months) and in comparison with the general population. 2 studies with a retrospective cohort and seroepidemiological cross-sectional design were carried out. Questionnaires were completed by 401 caregivers in 36% of all WIZO day-care centers. As a measure of past exposure to Shigella, levels of S. sonnei and S. flexneri antibodies were examined in the blood of 110 caregivers (ELISA method).

There was a higher incidence of diarrhea among young children, increasing the potential exposure to diarrheal agents among their caregivers. Nevertheless, no statistically significant differences in diarrhea incidence were found among caregivers of the various age groups during the previous year (p=0.768) and during the previous month (p=0.319), nor in absenteeism due to diarrhea during the last month (p=0.761). Levels of Shigella antibodies were similar among caregivers in all 3 groups. Diarrheal incidence was higher among women in the population control group than among caregivers during the previous year (p=0.005) and month (p=0.067). No statistically significant differences in levels of S. sonnei and S. flexneri antibodies were found between caregivers and women in the control group.

There was no evidence that diarrhea is an occupational hazard for caregivers of young children. An explanation may be the development of protective immunity against common diarrheal agents due to recurrent exposure.
 

Comparison between Every-Day and Every-3-Days Fluoxetine in Young, Moderately Depressed Out-Patients

A. Shiber, H. Reuveni, A. Elhayany, I.Z. Ben-Zion

Psychiatric Dept., Psychiatric Division, Soroka Medical Center and Ben-Gurion University of the Negev, Beer Sheba; and Medical Division for Drug Utilization, Kupat Holim Klalit (Sick Fund)

Fluoxetine is now a well-known and often-used specific serotonin reuptake inhibitor (SSRI) and antidepressant. It has a very long active half- life, from 2-16 days. Our hypothesis was that sufficient therapeutic effectiveness would be achieved by prescribing the drug less frequently than once a day.

To establish whether there is a difference between fluoxetine given daily or every 3 days, we assigned 25 outpatients with mild to moderate, acute major depressions (DSM-IV) to receive fluoxetine (20 mg), either each day or every 3 days. The study was open-labelled, using for assessment the HAM-D, GHQ-28 side-effect checklist and clinical judgment questionnaires. Follow-up lasted 6 months.

Results indicated no differences in the clinical outcomes, except for slightly fewer side-effects in the study group. Although the open label design limits drawing definitive conclusions, our preliminary results provide more information, and support our hypothesis that low-dosage fluoxetine is beneficial. However, more comprehensive, double-blind studies are necessary to confirm our preliminary results.

Experience with Under-Water Birth

Eylon Lachman, Zvi Finelt

Dept. of Obstetrics and Gynecology, Yoseftal Hospital, Eilat

Underwater birth is now deemed an acceptable type of delivery. Safety is a recurring consideration, the main concern being that of drowning. But in reports of 19,000 underwater births no untoward events were noted. Also, need for pain relief and of intervention during labor were both reduced. The short term indicators of neonatal outcome were good. A recent review explains 5 different physiological factors which inhibit initiation of fetal breathing under warm water. Many studies have shown no increase in risk of infection of either mother or baby. We report our experience with 26 women, 23 of whom actually delivered in the pool with excellent results. We believe that birth under water is safe and beneficial if done properly for low-risk patients.

Incomplete Penile Amputation: Diagnostic and Therapeutic Challenge

D. Leibovici, B. Yaffe, A. Zisman

Urology Dept., Assaf Harofeh Medical Center and Microsurgery Dept., Chaim Sheba Medical Center, Tel Hashomer

Traumatic penile amputation is a severe injury associated with a potential for multidisciplinary dysfunction. Since such injuries are rare, diagnostic and therapeutic experience is minimal. While complete penile amputation is a straight-forward diagnosis, incomplete amputations are not as evident and diagnosis may be delayed. The therapeutic endpoint includes restoration of an acceptable appearance of the phallus and a urethral meatus that allows normal voiding. Other objectives include re-establishment of sexual potency and fertility. As in other amputations, the treatment of choice is meticulous microsurgical replantation, including re-anastomosis of dorsal and cavernosal arteries, the deep dorsal vein, the urethra and nerves, as well as suturing the tunica albuginea. While appropriate cosmetic results and normal voiding can be achieved in most cases, potency is less frequently achieved due to neurological deficit leading to impaired erection and loss of sensation. Penile amputation is thus a complex therapeutic challenge, as meticulous anatomic reconstruction of blood vessels and nerves is essential for restoration of function. Since incomplete penile amputation may be overlooked when other more obvious injuries draw attention, this injury should be suspected in all cases of penetrating injury of the male genitalia. We present a 17-year-old man who sustained an incomplete penile amputation in a traffic accident.

Radiotherapy of Localized Prostatic Carcinoma

Eliahu Gez, Yael Netzer-Horowitz, Einat Waiman, Raphael Rubinov, Yoram Cohen, Abraham Kuten

Northern Israel Oncology Center and Oncology Dept., Rambam Medical Center and Lin Medical Center, Haifa; and Soroka Medical Center, Beer Sheba

112 patients with localized prostate cancer, clinical stage A2-C, were treated by definitive radiotherapy between 1982-1988. Radiation volume encompassed the prostate, seminal vesicles and pelvic lymph nodes. The 10-year actuarial survival figures were: overall 51%; stage A2 87%; stage B 50%; stage C 36%; well differential tumors 67%; moderately differentiated 50%; poorly differentiated 32%; patients with local tumor control 55%; and patients with minimal local control 36%. It is concluded that external beam irradiation is effective in localized prostatic cancer. Stage and grade are prognosticators of survival.

Effect of the Yom Kippur Fast on Parturition

A. Wiser, E. Maymon, M. Mazor, I. Shoham-Vardi, T. Silberstein, A. Wiznitzer, M. Katz

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

Food-withdrawal has been proposed as a possible mechanism for initiating the onset of labor in animals and humans. The hypothesis was based upon the reported increase in deliveries of infants during the Yom Kippur fast. We studied the effect of the fast on full term deliveries of Jewish women, with non-fasting Bedouin women as controls (1988-1995, 1,313 Jewish and 1,091 Bedouin deliveries). To determine the effect of Yom Kippur itself, delivery rates on Sukkot and Yom Kippur were compared in both groups. The mean delivery rate in the Jewish population was significantly higher during Yom Kippur and the day after, than during the 7 days before Yom Kippur (15.1±5.1 and 14.6±4.7 vs 10.7±3.5, p<0.04 and p<0.01, respectively). There was an increase in delivery rate during the 6 hours before the end of the fast. In the Bedouin women there were no changes in delivery rate during any of these periods. There were no significant differences in the rates of deliveries during the Sukkot festival between Jewish and Bedouin women. We conclude that fasting is associated with a significant increase in the rate of deliveries at term.

Hyponatremia due to Prolonged Excessive Ingestion of Water

I. Shavit, J. Diment, S. Ravid, N. Shehadeh

Dept. of Pediatrics A, Rambam Medical Center and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

We report a 1.5-year-old boy admitted for restlessness and constipation. He was found to have hyponatremia caused by voluntary drinking of excessive amounts of water. Although unusual in children, intoxication by oral water is a recognized clinical syndrome in infants, 3-6 months old, fed with dilute formula. Water intoxication in older children is rare. The diagnosis was established by the water deprivation test.

Red Cell Na+/H+ Exchange and Role of Protein Kinase C in its Stimu-Lation in Diabetes Mellitus, Essential Hypertension and Nephropathy

Wladimir Koren, Robert Koldanov, Edna Peleg, Eva Izsak, Meir Berezin, Talma Rosenthal

Dept. of Medicine C, Hypertension Unit and Endocrinology Institute, Chaim Sheba Medical Center, Tel Hashomer

Na+/H+ exchange (NHE) was measured as maximal initial velocity of pH-dependent H+ efflux from red cells into an alkaline medium containing Na+ in patients with insulin-dependent or noninsulin-dependent diabetes, with and without hypertension and in normoglycemic, essential hypertensives and normal controls (50 subjects in each subgroup). Maximal velocities of NHE were found in microalbuminuric patients in all subgroups, and NHE correlated with the rate of microalbuminuria (r=0.61, p=0.02). Daily insulin requirements were greater in those with elevated NHE (84±8 vs 42±4 U/day). There was no correlation between NHE and levels of plasma glucose, HbA1 and plasma aldosterone and lipid profile and PRA. NHE was correlated with plasma prolactin (r=0.51, p=0.02) and PTH r=0.24, p=0.05). In uremic patients, NHE was inversively correlated with creatinine clearance (r=-0.48, p=0.03). Since calphostin C, a selective inhibitor of protein kinase C, lowered increased NHE in vitro, the protein kinase C-dependent pathway of the exchanger regulation was concluded to be responsible for NHE activation in diabetes mellitus and essential hypertension.

Water Intoxication following Desmopressin Overdose

D. Segal-Kuperschmit, O. Dali-Gotfrid, A. Luder

Pediatric Dept., Rebecca Sieff Hospital, Safed

Water intoxication is a serious condition which may be caused by desmopressin overdose, with reversible or irreversible neurological complications. In the past, desmopressin was used in endocrinological centers for the treatment of anti-diuretic hormone deficiency (central diabetes insipidus). Indications for hormone treatment have since widened, especially as an effective solution for nocturnal enuresis. It is now often prescribed in community clinics, and its use has been encouraged by extensive promotion. We describe a 15-year-old boy with primary nocturnal enuresis who started treatment with desmopressin 1 year prior to admission. He was allowed to use the drug without supervision, and drank excessively. The result was water intoxication which required admission for intensive care because of loss of consciousness and convulsions for 36 hours.

Recurrent Late Hemarthrosis after Total Knee Replacement

David Hendel, Gad J. Velan

Dept. of Orthopedics, Rabin Medical Center, Golda Campus, Petah Tikva

A patient who had a successful total knee replacement for severe degenerative osteoarthritis of the right knee had an excellent functional result. 2 years after the operation there was spontaneous intra-articular bleeding that was treated successfully conservatively. Recurrent hemarthrosis 2 months later was treated similarly and also resolved without residual functional impairment after a follow-up of over 1 year. Recurrent late hemarthrosis in the knee is a fairly rare complication following total knee arthroplasty, but is amenable to conservative measures. Frequently, persistent recurrent hemarthrosis requires debridement of the bleeding synovium of the knee.