Biomedical subjects
A Brzezinski
Publications and source records attributed to A Brzezinski.
The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis.
BACKGROUND & AIMS: Two case-control studies have shown that folate may protect against neoplasia in ulcerative colitis. This historical cohort study was performed to better define this association. METHODS: The records of 98 patients with ulcerative colitis who had disease proximal to the splenic flexure for at least 8 years were reviewed. Documented folate use of at least 6 months was deemed a positive exposure. RESULTS: Of the patients, 29.6% developed neoplasia and 40.2% took folate supplements. The adjusted relative risk (RR) of neoplasia for patients taking folate was 0.72 (95% confidence interval [CI], 0.28-1.83). The dose of folate varied with the risk of neoplasia (RR, 0.54 for 1.0 mg folate; RR, 0.76 for 0.4 mg folate in a multivitamin compared with patients taking no folate). Folate use also varied with the degree of dysplasia (RR for cancer, 0.45; RR for high-grade dysplasia, 0.52; RR for low-grade dysplasia, 0.75 compared with patients with no dysplasia) (P = 0.08). CONCLUSIONS: Although not statistically significant, the RR for folate supplementation on the risk of neoplasia is < 1 and shows a dose-response effect, consistent with previous studies. Daily folate supplementation may protect against the development of neoplasia in ulcerative colitis.
Serotonin and premenstrual dysphoric disorder.
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Differential induction of cell-mediated mineralization in rat marrow stroma by sera from women of low and high risk for vertebral fracture.
The purpose of this study was to analyze the ability of sera to reflect the state of bone metabolism by testing the osteogenic response of mesenchymal cells in culture. Sera of 20 peri- and postmenopausal women were tested before the initiation of hormone replacement therapy. The responding cells were osteoprogenitors (OPC) of rat marrow stroma which normally respond to dexamethasone (DEX) and beta-glycerophosphate (beta GP) by proliferation, differentiation, and mineralization in culture. Instead of DEX, diluted sera (1:50) were applied to rat stromal cell cultures for analysis of their ability to affect cell proliferation, specific alkaline phosphatase (ALP) activity, and cell-mediated mineralization. The results were compared individually with the respective values of vertebral bone mineral density (BMD), expressed as the number of standard deviations above or below the mean BMD of reference populations (positive or negative Z-score). Serum donors were divided in two; the group with positive Z-scores was considered to have a low risk, and that with negative Z-scores was considered to have a higher risk for vertebral fractures. No significant difference was found between the two groups in the ability of their sera to induce cell proliferation or specific ALP activity. However, sera representing negative Z-scores induced sixteenfold less mineralization than those of positive Z-scores. The scatter of individual mineralization values was highly discriminatory between the two groups (alpha < 0.00). These results indicate that the serum-induced, cell-mediated mineralization in culture might be suitable for initial evaluation of fracture risk and thus deserve further investigation.
Misplaced confidences?
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Treatment of left-sided ulcerative colitis with butyrate enemas: a controlled trial.
BACKGROUND: The colonic mucosa is highly dependent upon the presence of luminal nutrients. This dependence is most marked in the distal colon. The major luminal nutrients are short chain fatty acids that are produced as a by-product of colonic fermentation of carbohydrates. Butyrate appears to be the short chain fatty acid most avidly metabolized by the colonic mucosa. It has been suggested that ulcerative colitis is, at least in part, related to an energy deficiency state of the colonic mucosa which may be secondary to impaired short chain fatty acid production, uptake or utilization. The objective of this study was to determine if butyrate given as enema therapy is effective in the treatment of active distal ulcerative colitis. METHODS: Thirty-eight patients with distal ulcerative colitis were randomly assigned to receive nightly butyrate (n = 19) or saline/placebo (n = 19) enemas. Butyrate enemas consisted of 60 mL of 80 mM sodium butyrate titrated to a pH of 7.0. Patients were assessed clinically and endoscopically at baseline and at 3 and 6 weeks follow-up. Pre- and post-treatment mucosal biopsies were assessed histologically. Response to therapy was determined by changes in a 12-point clinical disease activity index score based on patient symptoms, endoscopic mucosal appearance and physicians' global assessment. RESULTS: Clinical improvement was noted in seven of 19 (37%) butyrate-treated patients and nine of 19 (47%) placebo-treated patients (P = 0.51). Clinical remission was achieved in three patients in each group (16%). No toxicity was observed in either treatment arm. CONCLUSIONS: The results suggests that once nightly 60 mL butyrate enemas (80 mmol/L) are not efficacious in the treatment of distal ulcerative colitis.
Dyslipidaemia in polycystic ovarian syndrome: different groups, different aetiologies?
The objective was to study the pathophysiology of the dyslipidaemia in polycystic ovarian syndrome (PCOS) patients, and to determine how it is related to hyperinsulinaemia, hyperandrogenism and dehydroepiandrosterone sulphate (DHEA-S) concentrations. The lipoprotein lipid profile, anthropometric measurements, endocrine profile and the presence of insulin resistance were evaluated in 31 PCOS patients and 20 age-matched healthy women, who served as controls. PCOS patients had higher fasting insulin concentrations, higher body mass indexes (BMI) and were hyperlipidaemic, with higher total cholesterol, low density lipoprotein (LDL) and triglyceride (TG) concentrations. There were no relationships between plasma lipids and anthropometric variables in the patient group as a whole. Insulin-resistant (IR) and non-IR (NIR) PCOS patients were then evaluated separately. Obesity with marked hyperandrogenism were the predominant features in patients with IR. NIR patients were not obese and had significantly less hyperandrogenism. The adrenal androgen DHEA-S was at the upper limit of its normal range in both groups. However, both PCOS subgroups exhibited similar significant abnormalities in terms of their lipid parameters. Insulin and DHEA-S concentrations were positively correlated with total cholesterol, LDL and TG, and negatively correlated with high density lipoprotein, in IR patients. In NIR subjects, insulin was not correlated with any of the lipids and DHEA-S was negatively related to cholesterol and LDL. Anthropometric variables were related to lipids in only the NIR patients. Thus PCOS subjects as a group exhibit dyslipidaemia, characterized by increased total cholesterol, LDL and TG concentrations. When divided into IR and NIR subjects, there were no differences in the degree of lipid abnormalities, despite significant variations in the BMI and androgen status. Thus, in PCOS subjects, dyslipidaemia may occur irrespective of insulin resistance. Insulin and DHEA-S concentrations were positively correlated with an atherogenic lipid profile in the IR group only. As distinct from syndrome X when IR was present, dyslipidaemia was not related to body weight or the waist:hip ratio. In the NIR group there was no relationship between lipids and insulin; DHEA-S, on the other hand, was negatively related to cholesterol and LDL concentrations. Thus, dyslipidaemia in PCOS patients may occur irrespective of insulin resistance, and may have different metabolic aetiologies depending on DHEA-S metabolism. It remains to be seen whether the two types of PCOS are associated with different risks for ischaemic heart disease.
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.
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.
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.
Insulin resistant and non-resistant polycystic ovary syndrome represent two clinical and endocrinological subgroups.
We studied the clinical and endocrine features of 35 patients with polycystic ovary syndrome (PCOS) who are either insulin resistant or non-insulin resistant. The occurrence of insulin resistance was determined by measuring insulin and glucose concentrations following a standard 75 g oral glucose load. All patients were evaluated by anthropometric measurements: body mass index (BMI), percentage of body fat (BCF) and waist-to-hip ratio (W/H), degree of hirsutism (Ferriman-Gallwey method) and endocrine profile. Fourteen patients had insulin resistance of unknown origin whereas four were due to a type A insulin receptor mutation, and 17 were non-insulin resistant. The insulin resistant patients were significantly more obese (higher BMI P < 0.0001, BCF P < 0.002 and W/H ratio P < 0.005) and were more hirsute (P < 0.002) than the non-insulin resistant patients. Testosterone concentrations were significantly higher in the insulin resistant group than in the non-insulin resistant group (2.65 versus 1.37 nmol/l; P < 0.027), whereas sex hormone-binding globulin was lower in insulin resistant patients (30.61 versus 19.48 nmol/l; P < 0.02). Non-insulin resistant patients showed a high luteinizing hormone to follicle stimulating hormone ratio, while a normal ratio was found in the insulin resistant subpopulation (2.94 versus 1.34; P < 0.0001). We concluded that PCOS comprises two subpopulations, one with insulin resistance of different aetiologies and the other which has no insulin resistance. These two groups differ in their anthropometric and endocrine features. The diagnosis of insulin resistance in PCOS can be easily determined by the insulin response to an oral glucose tolerance test.
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.
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.
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.
A 'menopause score' for postmenopausal hormone replacement therapy.
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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.
Cancer mortality rates in ulcerative colitis surveillance programs.
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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.