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Biomedical subjects

A Brzezinski

Publications and source records attributed to A Brzezinski.

At least 37 records · Page 2Linked to original sources

The risk for cancer or dysplasia in ulcerative colitis patients with primary sclerosing cholangitis.

OBJECTIVES: Recent studies have implicated primary sclerosing cholangitis (PSC) as a risk factor for colorectal cancer (CRC) in ulcerative colitis (UC). Our study was designed to define both the risk and the risk factors for CRC or dysplasia in a large UC cohort with PSC. METHODS: Patients with UC and PSC were compared with a random sample of UC controls without PSC. Patients were analyzed from the inception of disease until an outcome or censor. RESULTS: Thirty-three (25%) of 132 UC patients with PSC developed CRC or dysplasia compared with 11 (5.6%) of 196 controls (adjusted relative risk 3.15, 95% confidence interval 1.37-7.27). Possible risk factors were chronic disease activity and lack of folate supplementation. Of 17 CRCs in the PSC group, 76% occurred proximal to the splenic flexure and 35% presented at an advanced stage, compared with one of five (20%) CRCs in controls being proximal and none being advanced. Six (4.5%) PSC patients, and no controls, died of CRC (p < 0.01). CONCLUSIONS: UC patients with PSC are at increased risk of developing CRC or dysplasia. Chronically active disease may be a risk factor, whereas folate could have a protective effect. CRCs associated with PSC are more likely to be proximal, to be diagnosed at a more advanced stage, and to be fatal.

Adult↗

Supranormal renographic differential renal function in congenital hydronephrosis: fact, not artifact.

PURPOSE: Children with unilateral hydronephrosis, who had been prospectively examined with diethylenetriaminepentaacetic acid (DTPA) and dimercapto-succinic acid (DMSA) renography, were evaluated to determine whether supranormal renographic differential renal function exists. MATERIALS AND METHODS: A total of 54 children with congenital single system hydronephrosis underwent abdominal ultrasound, voiding cystourethrogram, and DTPA and DMSA renal scans. None had abnormalities of the bladder or contralateral kidney. Differential renal function greater than 55% was defined as supranormal. RESULTS: Of the 54 patients 15 (28%) with a median age of 4 months (range 0.5 to 66) were identified with supranormal renographic renal function on either DTPA or DMSA. Supranormal renographic renal function was detected by DMSA in 9 cases (mean 57+/-2%), DTPA in 8 (mean 58+/-2%) and both in 2 (mean 57+/-2%). Average function demonstrated in the 15 patients was 55+/-3% (range 51 to 62) with DMSA which was not different from that found with DTPA (mean 55+/-4%, range 46 to 61%). The kidneys with supranormal renographic renal function were significantly larger than hydronephrotic controls according to longitudinal parenchymal area on DMSA. Mean followup was 20 months for 13 patients, with 8 of 13 (62%) undergoing pyeloplasty. Followup DTPA renal scans available in 9 children revealed persistent supranormal function in 6, despite pyeloplasty in 3. CONCLUSIONS: Supranormal renographic differential renal function does exist in congenital hydronephrosis and when found the kidneys are consistently enlarged. The position of supranormal renographic renal function in the management algorithm of hydronephrosis remains to be elucidated as it does not appear to be a benign prognostic factor.

Child, Preschool↗

Periurethral injection for the treatment of urinary incontinence.

Periurethral injection of substrates that compress, support, or narrow the bladder neck for the treatment of stress incontinence is not new. Several injectable compounds have been used in a small number of patients during the 1940s and through the 1960s; however, the results were not very successful and often led to significant complications. More recently, two major materials have been developed that seem to be useful in treating stress incontinence by periurethral injection: Polytef paste and GAX collagen. Other injectables include autologous fat tissue and silicone microimplants. The most suitable patients for periurethral injection are elderly women, patients who constitute high operative risk, and those with stress incontinence due to intrinsic sphincter failure. Patients with stress incontinence due to a combination of urethral hypermobility and intrinsic sphincter deficiency with failure of suspension procedure may also benefit from the procedure. The reported long-term (more than 24 months) success rates according to the various substances are as follows: Teflon (Polytef) (E.I.du Pont de Nemours and Co, Wilmington, DE): 30 to 38 percent cured or improved; repeated injections usually do not improve the outcome; mostly minor complications with case reports of more serious side effects such as periurethral granuloma formation and bladder outlet obstruction. GAX collagen: 69 to 77 percent subjectively cured or improved after 24 months; 54 to 57 percent objectively cured or improved, the reported morbidity in these procedures is minimal; repeated injections can improve the outcome. The experience with autologous fat and silicone microimplants is insufficient, with an overall success rate of 70 percent (1-40 months follow-up; mean 12 months) and 58 to 70 percent (17-36 months), respectively. Most of the procedures are performed as outpatient cases, and some under local anesthesia. These procedures are minimally invasive, usually safe and well tolerated, require shorter hospitalization, and are cost effective. In conclusion, in carefully selected patients, periurethral injection seems to be a reasonable option in the modern treatment of female stress incontinence.

Adipose Tissue↗

"Melatonin replacement therapy" for postmenopausal women: is it justified?

OBJECTIVE: Aging, sleep, and breast cancer are important concerns of postmenopausal women. There now is evidence that melatonin, the hormone secreted by the pineal gland, may have a role in the regulation of various human biological processes including sleep, tumor growth, and perhaps aging. The current knowledge concerning these questions is briefly and critically reviewed. CONCLUSIONS: Melatonin might be implicated in menopause-associated processes such as insomnia, breast cancer, and general aging. Its beneficial effect on sleep has been demonstrated in controlled clinical trials, however, "melatonin replacement therapy" for all postmenopausal women is currently unjustified.

Aging↗

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.

Adult↗

Ritualistic female genital mutilation: current status and future outlook.

Ritualistic sexual mutilation of females dates back to the fifth century B.C. This traditional practice is a social as well as a health issue that affects the physical and mental well being of the women who undergo it. Although practiced mostly in African countries north of the equator and the Middle-East, concern has recently been expressed that female genital mutilation is also being practiced in the U.S., Europe, and other western countries by immigrants from these countries. This review describes the various types of female genital mutilation and presents the historical and cultural background of the tradition, outlines the medical, psychological and sexual problems, and discusses the current status and future outlook for this tradition, emphasizing social, medical, and legislative aspects.

Africa↗

Induction of ovulation and risk of breast cancer: an overview and perspectives.

The modern techniques for assisted reproduction have exposed many women to potent follicular stimulation regimens. Follicular stimulation is associated with an exposure to potent fertility drugs and abnormal estrogen, progesterone and human chorionic gonadotropin (hCG) concentrations. These treatments and hormones might affect the proliferation of epithelial breast cells and thus the risk of breast cancer. The possible effects of ovarian stimulation on the incidence and course of human breast cancer, and the need for long-term cohort studies is discussed.

Adult↗

Long-term results of percutaneous endopyelotomy in the treatment of children with failed open pyeloplasty.

PURPOSE: We reviewed our experience with the safety and long-term efficacy of percutaneous endopyelotomy in children with secondary ureteropelvic junction obstruction who previously underwent open pyeloplasty. MATERIALS AND METHODS: Nine patients a median of 7 years old underwent endopyelotomy between June 1985 and July 1995. Anderson-Hynes pyeloplasty had previously been performed in all children. Antegrade endopyelotomy was done with a cold knife in conjunction with balloon dilation in some cases. Postoperative stenting lasted 6 weeks. RESULTS: The median interval between pyeloplasty and endopyelotomy was 7.5 months. Mean operative time was 240 minutes. Percutaneous endopyelotomy was successful in 8 of the 9 patients. One patient who required repeat endopyelotomy after 4 years is presently well at 5 years of followup. Average followup was 5.6 years (range 2 to 10). There was a low morbidity rate, including 1 case of urinary tract infection, 1 of pneumonia and 1 that required blood transfusion. CONCLUSIONS: Percutaneous antegrade endopyelotomy is a safe, effective and durable alternative for children who previously underwent unsuccessful pyeloplasty.

Adolescent↗

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.

Alkaline Phosphatase↗

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.

Adult↗

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.

Adult↗

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↗