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Biomedical subjects

A Brzezinski

Publications and source records attributed to A Brzezinski.

At least 19 recordsLinked to original sources

Hypotheses: melatonin/steroid combination contraceptives will prevent breast cancer.

The use of the conventional combination oral contraceptives (containing ethinyl-estradiol and a progestin) is associated with reduced risk of ovarian and endometrial cancer. However, prolonged use of these pills before first term pregnancy apparently increases the risk of pre menopausal breast cancer. We propose that the pineal gland hormone melatonin, combined with a progestin, as a new and novel oral contraceptive combination might prevent breast cancer in long term users. This hypothesis is based on the assumption that women have a propensity to develop breast cancer which correlates with number of ovulatory cycles over their lifetime. In evolution, the phylogenetic point at which women became sensitive to breast cancer evolved at a transfer point of the mechanism of ovulation from seasonal ovulation, which is still common in many mammalian species, to the current human pattern of continuous ovulatory cycles. We suggest that melatonin/ovarian-steroid contraceptive will restore the lost mechanism of endogenous anovulation, and thus, by preventing continuous epithelial breast cell proliferation, will reduce the risk of breast cancer in long-term users.

Breast Neoplasms

Effects of low-dose estrogen oral contraceptives on weight, body composition, and fat distribution in young women.

OBJECTIVE: To determine prospectively whether the use of low-dose estrogen oral contraceptives (OC) is associated with changes in weight, body composition, or fat distribution. DESIGN: Anthropometric measurements were performed in 49 healthy young (16 to 21 years old) women before commencement of OC use (30 micrograms ethinyl estradiol [EF2] plus 75 micrograms gestodene) and after three and six treatment cycles. Thirty one age- and weight-matched women who were not using OC served as controls. SETTING: Outpatient gynecological clinic of Hadassah Medical Center, a tertiary level hospital, and the "Shilo" voluntary service for the prevention of unwanted pregnancy. MAIN OUTCOME MEASURES: Anthropometric measurements included body mass index (BMI), waist-to-hip girth ratio, and body composition (the percentage of body fat and water), estimated by mean of infrared interactance. RESULTS: In the group of OC users, baseline BMI, percent fat, percent water, and waist-to-hip girth ratio were 21.1 +/- 0.32 (kg/m2), 23.8% +/- 0.63%, 57.4% +/- 0.39%, and 0.73 +/- 0.01, respectively, and did not change significantly after six cycles (20.6 +/- 0.41 [kg/m2], 23.9% +/- 0.57%, 58.1% +/- 0.49%, and 0.72 +/- 0.03, respectively). These measurements were not significantly different when compared with the nonusers. Fifteen OC users (30.6%) gained weight (> 0.5 kg). Weight gain was due to a significant accumulation of fat (from 22.5% +/- 1.1% to 25.6% +/- 0.74%), whereas the percentage of body water remained stable. The waist-to-hip girth ratio also was not changed significantly. Similarly, 11 nonusers (35.4%) gained weight because of similar nonabdominal fat accumulation. Ten OC users (20.4%) lost weight (57 kg +/- 1.51 to 55.4 +/- 1.47 [mean +/- SEM]) and 6 nonusers (19.3%) also lost weight (59 kg +/- 1.42 to 57.3 +/- 1.92). In both groups the loss of weight was not associated with significant change in body composition. CONCLUSIONS: The use of low-dose OC (EE2 plus gestodene) was not associated with overall impact on weight, body composition, or fat distribution. However, when weight gain did occur during OC use, it was due to increase in body fat and not in volume of body water, and it was not associated with changes in fat distribution.

Adipose Tissue

Effects of hormone replacement therapy on weight, body composition, fat distribution, and food intake in early postmenopausal women: a prospective study.

OBJECTIVE: To evaluate the effects of hormone replacement therapy (HRT) on body weight and composition, fat distribution, and food intake in women entering the climacteric. DESIGN: Prospective clinical study. SETTING: Outpatient menopause clinic at a tertiary medical center. PARTICIPANTS: Sixty-three early postmenopausal women (44 to 54 years old) were prospectively studied for 1 year. They consisted of two groups: group A, 34 subjects who initiated continuous estrogen and progestin treatment (daily oral conjugated estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg), and group B, 29 women who refused hormonal therapy and served as controls. The age, menopausal status, initial anthropometric measurements (weight, body mass index [BMI], fat mass, and waist-to-hip girth ratio), and daily food intake (total caloric intake and food composition) were similar in both groups. INTERVENTIONS: Anthropometric measurements were performed before commencement of HRT use and after 12 months. MAIN OUTCOME MEASURES: Anthropometric measurements included BMI, waist-to-hip girth ratio, and body composition (the percentage of body fat and water) estimated by means of infrared interactance. Daily food intake was also recorded. RESULTS: The body weight and fat mass increased significantly in both the treatment (73.22 +/- 2.01 [mean +/- SE] to 75.57 +/- 1.12 kg) and the control group (71.45 +/- 3.11 to 73.51 +/- 1.23 kg). However, a significant shift from gynoid to android fat distribution was observed only in the control group (waist-to-hip ratio shifted from 0.80 +/- 0.01 to 0.85 +/- 0.01), whereas no significant change was observed in the treatment group (0.81 +/- 0.01 to 0.82 +/- 0.01). Caloric and macronutrient intake did not change in either group. CONCLUSIONS: These results indicate that continuous daily estrogen and progestin replacement therapy neither prevents nor increases early postmenopausal weight gain and fat accumulation. However, it does minimize the shift from gynoid to android fat distribution.

Adult

Worsening risk for the development of dysplasia or cancer in patients with chronic ulcerative colitis.

OBJECTIVES: Patients with ulcerative colitis (UC) are at increased risk for developing dysplasia or cancer (neoplasia) and are usually offered colonoscopic surveillance to reduce their risk of cancer-related mortality. The causes of neoplasia may be related to features of UC (the extent, severity, activity, and age at onset of the disease) and to environmental factors (medications, vitamin and mineral supplementation, diet, or industrial pollutants). To determine whether and how the risk (and hence the risk factor profile) for the development of neoplasia changes over time, we conducted an historical cohort study. METHODS: From 445 adult patients with UC proximal to the splenic flexure seen in the Department of Gastroenterology between 1986 and 1992, a random sample of 209 patients was selected. Patients with UC for less than 8 yr or colectomy or neoplasia detected within 2 yr of referral were excluded, leaving 98 patients in the cohort, half of whom had disease onset during or before 1972. RESULTS: After controlling for age at disease onset and duration of disease at first colonoscopy, we found that patients with an earlier year of disease onset were 85% less likely to develop neoplasia than patients with a later year of disease onset (hazard rate ratio 0.15, 95% confidence interval 0.03-0.66). CONCLUSION: These data suggest that the risk for developing neoplasia in UC patients increases with increasing calendar year, implying a worsening risk factor profile.

Adult

Current status of endoscopic surgical management of tubal pregnancy.

A worldwide increase in the incidence of ectopic pregnancy has been reported in the last two decades. Recently developed diagnostic tools markedly improved the early diagnosis capability. These include: 1, rapid and sensitive beta hCG and progesterone assays; 2, improved ultrasonographic visualization of the pelvic organs; 3, the wide application of diagnostic laparoscopy. Today, most cases are diagnosed before a rupture occurs. Accordingly, treatment has shifted from an immediate, life-saving intervention to conservative methods of management, directed at preserving fertility and reducing morbidity. Endoscopic surgical techniques have also rapidly improved in the last decade, thus, this treatment option apparently became the treatment of choice in most centers. Laparoscopic conservative treatment of tubal pregnancy is as effective and safe as treatment with laparotomy and has the advantage of decrease in hospital stay, cost, and delay in return to normal activity. This review will focus on the endoscopic surgical procedures and their place in view of the other surgical and non-surgical options.

Chorionic Gonadotropin

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.

Adult

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.

Adult

Alcohol sclerosis for polycystic liver disease and obstructive jaundice: use of a nasobiliary catheter.

We report the use of a nasobiliary catheter in the management of a 55-yr-old female with autosomal dominant polycystic kidney disease who developed obstructive jaundice from a hepatic cyst. The patient presented with a 2-wk history of fatigue, jaundice, nausea, vomiting, and abdominal pain. Physical examination was remarkable for tender hepatomegaly. Computerized tomography revealed multiple hepatic cysts and dilated intrahepatic biliary radicles. Endoscopic stent placement failed to relieve the obstruction. Computerized tomography guided percutaneous aspiration of the obstructing hepatic cyst was successful with the aid of a nasobiliary cholangiogram allowing visualization of the biliary tree and identification of the obstructing hepatic cyst. However, the cyst rapidly accumulated fluid, and the obstruction recurred within 1 wk of simple aspiration. Relief of symptoms was maintained only after alcohol sclerosis of the obstructing hepatic cyst. Review of the literature shows that alcohol sclerotherapy is a safe and effective nonsurgical means of treating symptomatic hepatic cysts.

Catheterization

Effects of melatonin on progesterone production by human granulosa lutein cells in culture.

OBJECTIVE: To test the hypothesis that melatonin modulates steroid synthesis in the human ovary. DESIGN: Granulosa lutein cells obtained from in vitro fertilization cycles were cultured in medium containing melatonin and human chorionic gonadotropin (hCG). RESULTS: Progesterone (P) secretion by granulosa lutein cells increased progressively in both basal and hCG-stimulated conditions, up to 96 hours in culture, plateaued at 144 and decreased thereafter. Melatonin (10(-7), 10(-9), 10(-11) M) had no effect on basal P or 17 beta-estradiol production. The addition of melatonin to the hCG-treated granulosa lutein cells significantly (P less than 0.05) potentiated the stimulatory effect of hCG on P production. The effect was most prominent after 144 and 196 hours of incubation. CONCLUSION: This observation suggests a role for melatonin in the intraovarian control of P production in the human ovary.

Cells, Cultured

Seasonality in human reproduction: an update.

A seasonal distribution in human natural conception and birth rates has been consistently demonstrated by epidemiological studies in several geographical areas. Possible hypotheses abound to explain this seasonality. Though a seasonal effect on reproduction is well-documented and has been extensively investigated in mammals, information concerning the influence of seasonal variation and its mechanism on human and primate reproduction is scarce. Recent evidence suggests that deterioration in sperm quality during the host summer in sub-equatorial areas, may result in lower conception rates leading to a reduction in the birth rate in spring. In northern countries, however, in regions where a strong seasonal contrast in luminosity exists, activity of the anterior pituitary-ovarian axis and the conception rate are decreased during the dark winter months. In these areas, inversely, a peak in conception rate during summer leading to a maximum in birth rate in spring has been observed. It is believed that seasonality in the ovulation rate may cause this variability. However, changes in the quality of the ovum or in endometrial receptivity which may lead to a greater waste of ovulated eggs and peri-implantation conceptuses at specific times of the year, have also been suggested. These phenomena might have important implications for in-vitro fertilization and gamete intra-Fallopian transfer as well as infertility in general. The seasonal effects, which may influence primate and human fertility and reproduction and its possible mediators, are critically reviewed.

Animals

Use of a urethral splent in one-stage hypospadias repair.

Over a 9-month period, 28 patients with distal penile or more proximal hypospadias underwent one-stage surgical repair. Bladder drainage was achieved in the traditional fashion with either an indwelling Foley catheter or suprapubic catheter or by using a modified urethral silicone stent ("splent"). Twenty-two patients had repair with a perimeatal skin flap, and the remaining six patients had major urethral reconstruction with a vascularized preputial island flap. Use of the urethral splent was associated with shorter postoperative hospitalization and minimal short-term complications. The authors' experience has shown that use of a urethral splent for urinary drainage is efficient and effective in postoperative management after hypospadias repair.

Catheters, Indwelling

Ovarian response to exogenous gonadotropins during pregnancy.

Multiple ovarian follicles were successfully induced in a patient undergoing superovulation for a gamete intrafallopian transfer (GIFT) procedure despite the presence of an undiagnosed ectopic pregnancy. Midluteal gonadotropin releasing hormone agonist (GnRH-a) treatment should be coupled with mechanical contraception in the previous cycle in patients with patent tubes.

Adult