[Rational use of albumin].

The use of albumin has been a matter of debate since its introduction in the 1940's. Albumin is not only expensive but may also be harmful when administered inappropriately. Until recently our use of albumin was controlled by a number of authorized physicians who signed all albumin prescriptions. In August 1998, a multidisciplinary team reviewed the indications for albumin use and introduced simple guidelines for its supply and administration. As a result, the use of albumin has decreased by almost 70%. This indicates that rational use of albumin can be achieved by appropriate guidelines, without requiring administrative limitations. We believe that this conclusion holds true for other diagnostic and therapeutic procedures as well.

[Ovarian cancer in Israel, 1960-1989].

In Israel ovarian cancer ranks among the most common malignant diseases in women. It is also one of the main causes of death from cancer in females in this country. Our population is composed of immigrants from diverse social, cultural, and geographical backgrounds, and only a sector of the inhabitants, mainly the younger generation, is Israeli-born. This study evaluates the trends of epidemiological and clinical data on ovarian cancer during 3 decades, 1960-1989, and includes a total of 5,786 cases of ovarian cancer. Information was obtained from the Central Israel Cancer Registry of the Ministry of Health and from the Central Bureau of Statistics. The incidence was stable during the survey period and was about 15-17/100,000 in women over the age of 15. Most (90%) were diagnosed over the age of 40. In women of European/American origin the incidence of ovarian cancer is 3 times greater than in women of Asian/African origin. The rate in the Israeli-born is between those of the other 2 groups, but closer to that of the European/American group. Over 70% were diagnosed with advanced disease (stage III-IV). Prognosis improved during the period of the study: 5-year survival was 19% in the early 60's and 31% in the 80's. During the last decade of the survey improvement was mainly in 2-year survival (from 38.5% to 60%).

Report of a continuous quality improvement program in a tertiary-care medical center.

OBJECTIVE/DESIGN: Changes in the health system in Israel have led to an increasingly competitive environment, decentralization, and economic constraints. We evaluated the use of a continuous quality improvement (CQI) program. SETTING: Three medical departments and three administrative wings in a 700-bed, tertiary-care, teaching hospital in Jerusalem. INTERVENTION: The program was planned as a short-term pilot project for long-term extension throughout the institution. The objectives were improved institutional efficiency and provision for change. The program was implemented through departmental improvement teams under a hospital management team and a steering committee, guided by an outside consultant firm. RESULTS: The Orthopedics Department experienced a 3-day reduction in patient length of stay (P<.008). The Emergency Room experienced a significant reduction in time to discharge through reduced waiting times for consulting physicians (P<.007) and for blood tests (P<.001). The Office of Patient Admissions streamlined procedures for admission and discharge, accomplished physical restructuring, and installed a telephone hot line. In Medical Records, a significant improvement in records availability was realized. In Outpatient Clinics, reductions in waiting times were realized, but were not statistically significant. The Supply Division showed savings on monthly orders and increased efficiency, with 95% of orders completed promptly and accurately. CONCLUSIONS: Several factors were identified as essential to the success of the program, including staff cooperation and commitment. We conclude that the CQI program was a useful tool to help our tertiary-care medical center adjust to changes in the Israeli healthcare system. It also served as a valid vehicle for maintaining and furthering optimal quality of care.

Therapeutic approach to ovarian cysts in tamoxifen-treated women with breast cancer.

OBJECTIVES: To present our clinical experience with gonadotropin-releasing hormone agonist (GnRHa) treatment of tamoxifen-treated women who had developed ovarian cysts, and to discuss the diagnostic and therapeutic options in such cases. METHODS: The study included six tamoxifen-treated premenopausal women with breast cancer who developed ovarian cysts and were followed up by our outpatient clinic. Tamoxifen was administered orally (20 mg/day). All patients underwent a pelvic examination and vaginal ultrasound using a 5-MHz vaginal probe. Blood samples for serum gonadotropins, estradiol (E2) and CA 125 levels were collected at the time of the ovarian cyst detection and every month thereafter. After detection of an ovarian cyst, the women were treated by monthly injections of GnRHa. RESULTS: The patients' mean age was 44 years (range 37-51 years) and all had stage-II or -III breast cancer. The mean duration of tamoxifen administration at the time of ovarian cyst detection was 15 months (range 3-40 months). All six ovarian cysts were found to be simple cysts, measuring more than 30 x 30 mm. Serum E2 levels of the six patients at the time of ovarian cyst detection were between 939 and 1796 pg/ml and were suppressed to less than 25 pg/ml after GnRHa therapy. After between three and six monthly injections of GnRHa all six ovarian cysts disappeared. On follow-up 6 months later, all patients had a normal pelvic examination. CONCLUSION: The findings of this preliminary report suggest that GnRHa might be an appropriate treatment for tamoxifen-treated women who develop ovarian cysts. It was demonstrated that the GnRHa caused regression of the ovarian cysts and enabled continuation with the adjuvant tamoxifen treatment.

Ovarian cysts in premenopausal and postmenopausal tamoxifen-treated women with breast cancer.

OBJECTIVE: Our purpose was to investigate the frequency of ovarian cysts in tamoxifen-treated breast cancer patients. STUDY DESIGN: The study population included 95 consecutive tamoxifen-treated premenopausal and postmenopausal women with breast cancer who were followed up by the outpatient clinic at the Hadassah University Hospital between September 1990 and June 1992. Tamoxifen was administered orally (20 mg/day). All patients underwent a pelvic examination and vaginal ultrasonography with a 5 MHz vaginal probe. RESULTS: During the study 11 of 95 tamoxifen-treated breast cancer patients (11%) had ovarian cysts. Five cysts were detected in postmenopausal women (6.3% of the postmenopausal women) and six in premenopausal women (37.5% of the premenopausal women). In postmenopausal and premenopausal women the mean tamoxifen treatment interval was 19.4 +/- 7.8 months (range 4 to 48 months) and 28 +/- 6.1 months (range 12 to 54 months), respectively (p = 0.41). In 8 of the 11 patients the ovarian cystic enlargement disappeared after cessation of tamoxifen treatment. Two patients underwent laparotomy because of persistent cysts and the third because of a rapidly growing myoma. The three cysts were found to be benign. CONCLUSION: Ovarian cysts are a common side effect of tamoxifen treatment. The ovarian cysts can develop in tamoxifen-treated premenopausal as well as postmenopausal women with breast cancer. Most of the tamoxifen-associated cysts disappear after tamoxifen treatment is abandoned.

Cost analysis of in vitro fertilization.

In vitro fertilization (IVF) has become a routine tool in the arsenal of infertility treatments. Assisted reproductive techniques are expensive, as reflected by the current "take home baby" rate of about 15% per cycle, implying the need for repeated attempts until success is achieved. Israel, today is facing a major change in its health care system, including the necessity to define a national package of health care benefits. The issue of infertility and whether its treatment should be part of the "health basket" is in dispute. Therefore an exact cost analysis of IVF is important. Since the cost of an IVF cycle varies dramatically between countries, we sought an exact breakdown of the different components of the costs involved in an IVF cycle and in achieving an IVF child in Israel. The key question is not how much we spend on IVF cycles but what is the cost of a successful outcome, i.e., a healthy child. This study intends to answer this question, and to give the policy makers, at various levels of the health care system, a crucial tool for their decision-making process. The cost analysis includes direct and indirect costs. The direct costs are divided into fixed costs (labor, equipment, maintenance, depreciation, and overhead) and variable costs (laboratory tests, chemicals, disposable supplies, medications, and loss of working days by the couples). The indirect costs are the costs of premature IVF babies, hospitalization of the IVF pregnant women in a high risk unit, and the cost of complications of the procedure. According to our economic analysis, an IVF cycle in Israel costs $2,560, of which fixed costs are about 50%. The cost of a "take home baby" is $19,267, including direct and indirect costs.

Sperm donation in Israel.

Science and technology in the field of human reproduction present new legal, ethical and religious questions which do not always have immediate answers. The first step in the rapidly developed field of reproductive technology was the use of sperm donation (artificial insemination by donor, AID) and the establishment of sperm banks. The state of Israel faced these problems when the regulations for sperm donation were discussed. The fact that the main holy places for the three monotheistic religions are in Israel directly influences the make-up of the population constituents. Therefore, besides a majority of secular people, a high percentage of the population of Israel is very religious: Jews, Moslems and Christians. Thus any resolution relating to AID should take this demographic combination into account. The practice of AID is opposed by the different monotheistic religions. To avoid the conflict between secular and religious people, and between the different religions' perspectives, the legal problem of AID in Israel was solved not by laws but by regulations which were published by the Ministry of Health. The main idea behind this attitude is that the state and its authorities should not and do not deal with ethical or religious questions. Thus, the decision was left to the couples and to the donors. The regulations address technical requirements, health problems and confidential issues concerning the couple, the donor and the child. In this paper we present the different views relating to these problems as perceived by the different religions, and describe the solution that was accepted by the Israeli Ministry of Health.

Embryonic cultures but not embryos transplanted to the mouse's brain grow rapidly without immunosuppression.

Embryos and embryocultures can be successfully transplanted into various bodily organs. However immunosuppression or homogenicity are required for the success of such experimental manipulation. Since the brain is considered immunologically privileged, we transplanted 2-4 cell embryos of C57BL x BALB/c, embryonic stem cells (ES) or embryoid bodies (EB) cultures into the hippocampus of the heterogeneous mouse stock HS/IBg. Both ES and EB cultures developed into an extensive growth, eventually larger than the brain itself, causing the death of the host in less than 29 days. The growth was identified as teratoma, mostly made of immature cells and tissues of diverse origin. Thus, the overall histological picture was that of a malignant teratoma. On the other hand, no embryos were found at any time after the transplantation; apparently, they could not survive in the host brain. The growth rate and the relative lack of rejection suggest that the brain offers a unique medium for ES and EB cultures but, not to embryos.

[Program for operating teams for quality improvement of hospital services].

In mid-1992, improvement of quality of service was set as a major goal in the framework of a 5-year plan at this hospital. This subject was selected in preparation for a new era in health care emerging in the world in general, and in Israel in particular. 6 problematic departments with high potential for improvement were chosen for the first stage of implementing a total quality management program (TQM). The goal was to gain experience through the implementation of TQM in a few medical and nonmedical departments in preparation for implementing TQM in the entire hospital. This process is ongoing and the first conclusions and perspectives are now being studied by all involved.

Sex ratio in triplets.

Since the introduction of different ovulation induction regimens the incidence of triplet pregnancies increased from a spontaneous rate of about 1:10,000 to the frequency of nearly 1:1000. Sex ratio of trigemini and male/female proportion of the three newborns within the same triplet set is the amazing issue that we attempted to elucidate in the present study. Data on 36 women with triplet pregnancies delivered in our hospital and information regarding 2717 triplet pregnancies reported by 16 relevant papers were included in this study. 36 women delivered 63 (58%) male and 45 (42%) female babies. Triplet sets of same gender comprised 33% of all trigemini. Sex ratios (male/female) for the spontaneous, menotropin and clomiphene group were 2.00, 1.57 and 0.94 respectively. Homogenous male/female set ratio was 5.0, 2.0 and 0.5 in menotropin, spontaneous and clomiphene groups respectively. As the percentage of ovulation induction triplet pregnancies increased constantly from 0% to 100%, a decline in the fraction of homogenous gender triplet sets was observed--from 73% to 23%. It may be concluded that sex ratio in triplet newborns is divergent according to different publications with most of the authors reporting a male/female ratio of less than 1.00. Ovulation induction results in a lower proportion of homogenous sex triplets sets. Superovulation by menotropins cause a higher percentage of male triplet newborns when compared to ovulation induction by clomiphene.

Hyaluronic acid for preventing experimental postoperative intraperitoneal adhesions.

Adhesions, which form in > 60% of patients following major abdominopelvic surgery, are a common cause of morbidity and infertility in women. Hyaluronic acid is a naturally occurring polysaccharide that has been shown to be beneficial in ophthalmic surgery and as intraarticular injections. This study was designed to examine the use of hyaluronic acid as an agent for adhesion prevention after experimental abrasion of rat uterine horns and to explore its possible mechanism of action. Twenty-nine female Sabra rats were randomly assigned to either a saline (n = 13) or hyaluronic acid (n = 16) group. Adhesions were created by local abrasion of the uterine surfaces. Five milliliters of 1% hyaluronic acid or saline was instilled intraperitoneally. Three weeks later the animals were killed and subjected to a second laparotomy. Intraabdominal adhesions were graded on the basis of gross appearance using a scoring system from 0 to 5. The adhesion score in the animals treated with hyaluronic acid was significantly (P < .001) lower than that in the control animals. Hyaluronic acid did not affect the attachment or proliferation of fibroblasts but had an inhibitory effect on platelet aggregation in a dose-dependent manner. Intraperitoneal instillation of 1% hyaluronic acid significantly minimized adhesions formed experimentally. The mechanism of action may involve inhibition of platelet aggregation.

Ovarian stimulation and breast cancer: is there a link?

The results of both epidemiologic and experimental studies suggest that endogenous (and apparently exogenous) sex hormones and other reproductive variables have an important role in the development of human breast neoplasia. Nevertheless, no controlled study has ever addressed the possible effects of ovarian stimulation on the incidence and course of human breast cancer. Over the past decade the number of women undergoing follicular stimulation, especially during assisted reproductive technology procedures, has grown rapidly. Here we present 16 cases of young women who were treated by induction of ovulation, and subsequently were diagnosed with breast cancer. These women were drawn out of 950 cases of infertile women who underwent induction of ovulation at our fertility clinic over a 10-year period. The possible association between ovarian stimulation and promotion of breast cancer is discussed and the need for a controlled study is emphasized.

Hyperreactio luteinalis associated with non-immune hydrops fetalis--the role of pituitary hormones.

The level of pituitary hormones was measured in the serum and cysts' aspirate in a case of hyperreactio luteinalis (HL) complicating non-immune hydrops fetalis. The level of follicular stimulating hormone (FSH), prolactin and growth hormone (GH) was within normal range for pregnancy in both the serum and cysts' aspirate. The importance of increased luteinizing hormone (LH) level which was demonstrated in the cysts' fluid should further be determined.

Did anxiety during the Gulf War cause premature delivery?

The Persian Gulf War presented Israel with a threat of chemical attacks on the home front. There is no doubt, according to many publications, that the missile attacks caused extensive long-term stress on the Israeli population. In this research, the connection between environmental stress and preterm delivery was studied. One thousand twenty-two deliveries during the war were compared to 1,027 deliveries in the previous year. The two groups showed no differences in the average gestational age, the rate of premature labor, and the cesarean section rate. The percentage of instrumental deliveries using forceps or vacuum was significantly higher (p < 0.05) in the war group.

The effect of tamoxifen on the endometrium.

Tamoxifen is one of the most important treatments for breast cancer, especially in postmenopausal patients. It acts primarily as an anti-estrogenic agent, due to its cytoplasmic estrogen receptor binding capacity. However, it also exerts a mild estrogenic effect. Since the prolonged use of estrogen has been reported to increase the rate of benign and malignant changes in the endometrium, we evaluated whether there is a correlation between tamoxifen therapy and endometrial benign and malignant conditions. The study group comprised 95 patients with breast cancer who were treated with tamoxifen. No control group was examined. Patients underwent vaginal ultrasonography and endometrial biopsy in order to evaluate any changes in the endometrium occurring during tamoxifen therapy. Pathological changes were observed in 14 patients, 13 of whom were treated with tamoxifen for more than 12 months. Of these women, 3 were diagnosed with endometrial cancer, 3 had mild dysplasia, 3 had endometrial hyperplasia, and 4 had a benign endometrial polyp. Our findings indicate a significant correlation between long-term tamoxifen administration and endometrial proliferation. We therefore recommend that women treated with tamoxifen for more than 12 months have an annual vaginal ultrasonography and endometrial biopsy.

The Israel perinatal census.

A nation-wide perinatal census which included 22,815 deliveries was carried out. The cesarean section rate was 9.6% and the perinatal mortality rate was 13.5/1000. Using a logistic regression analysis the risk factors for cesarean section and for perinatal mortality were ranked. Breech presentation and one uterine scar were found to be the most important risk factors for cesarean section and breech presentation, maternal disease and multiple pregnancy for perinatal mortality. Low birth weight rate was 6.9% with nonsignificant differences between the various ethnic groups. The national cesarean section rate in breech presentation was 57.8%. It was performed mainly at the extremes of birth weight. From those with one previous cesarean section 55.1% delivered vaginally and 44.9% abdominally. The chance for vaginal delivery is higher (67.2%) providing the woman had delivered vaginally in the past. Comparison between primiparae and multiparae showed that preeclampsia, hypertension and diabetes mellitus were all significantly more frequent among older parturients and among primiparae.

PIP: During a period of 3 months, a nationwide perinatal census was carried out covering a total of 30 obstetric wards in 27 Israeli hospitals, and the records of all births from a questionnaire were prospectively examined. There were 22,815 births in the country. 90.4% of the deliveries were completed vaginally and 9.6% by Cesarean section (80% as an emergency procedure). The perinatal mortality rate was 13.5/1000. 1080 women who had one previous Cesarean birth were compared to 14,703 women with a previous vaginal birth. From those with one previous Cesarean section, 55.1% delivered vaginally and 44.9 abdominally. According to a logistic regression analysis, breech presentation and one uterine scar were the most important risk factors for Cesarean section as opposed to breech presentation, maternal disease, and multiple pregnancy for perinatal mortality. The national Cesarean section rate in breech presentation was 57.8%. The chance for vaginal delivery was 67.2%, provided the woman had delivered vaginally. The indication for a repeated cesarean section were a previous Cesarean section (28.7%) and malpresentation (12.8%). Uterine rupture ensued in 1.2% (13 cases) of post Cesarean women giving vaginal birth and in only .02% (4 cases) among those who had no previous Cesarean section (P0.001). Comparison between primiparas (42000 deliveries or 18.4% of the total) and multiparas showed that preeclampsia, hypertension, and diabetes mellitus were significantly more frequent among older patients. Preeclampsia and hypertension were more common among primiparas than multiparas (P0.001). In grand multiparity (7th or more parity) diabetes, hypertension, malpresentations, multiple births, large-for gestation age deliveries, and perinatal deaths were significantly more common. The mean birth weight was 3,222 +or- 551 g and the low birth weight (less than 2500 g) was 6.9% with nonsignificant differences between the various ethnic groups. Perinatal mortality was higher for infants born in breech presentation than in cephalic presentation, 23/1000 compared to 3.2/1000, respectively. The level of obstetrics in Israel was measured by the perinatal mortality and the Cesarean section rate was comparable to that of Great Britain, Norway, the Netherlands, and France.