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Biomedical subjects

H Barakat

Publications and source records attributed to H Barakat.

At least 19 recordsLinked to original sources

Presurgical diagnosis of posterior deep infiltrating endometriosis based on a standardized questionnaire.

BACKGROUND: To derive a diagnostic model based on symptoms and history as assessed by a standardized questionnaire to predict posterior deep infiltrating endometriosis (DIE) among women with chronic pelvic pain symptoms. METHODS: 134 women scheduled for laparoscopy for chronic pelvic pain symptoms completed a standardized self-administered questionnaire, specifically designed for the study. We compared the symptoms of the women with posterior DIE diagnosed at laparoscopy with those of the women with other disorders, and used multiple logistic regression analysis to select the best combination of symptoms for predicting posterior DIE. Cross-validation was performed with the jackknife method. RESULTS: 51 women (38.1%) were diagnosed with posterior DIE and 83 with other disorders (61.9%). The following variables were independent predictors for posterior DIE: painful defecation during menses, severe dyspareunia (visual analogic scale > or =8), pain other than noncyclic, and previous surgery for endometriosis. The cross-validation procedure leads to a simplified diagnostic model that uses two independent predictors: painful defecation during menses and severe dyspareunia. The sensitivity of this model for diagnosing posterior DIE was 74.5%, its specificity was 68.7%, its positive likelihood ratio was 2.4, and its negative likelihood ratio was 0.4. It correctly classified 70.9% of our sample into a high-risk (with either severe dyspareunia or painful defecation during menses) and a low-risk (neither symptom) group. CONCLUSIONS: Standardized evaluation of painful symptoms is useful for screening women so that they may have adequate exploration and counselling before laparoscopic surgery for pelvic pain symptoms.

Adult↗

Accuracy of rectal endoscopic ultrasonography and magnetic resonance imaging in the diagnosis of rectal involvement for patients presenting with deeply infiltrating endometriosis.

OBJECTIVE: To compare the accuracy of rectal endoscopic ultrasonography (REU) and magnetic resonance imaging (MRI) for predicting rectal wall involvement in patients presenting histologically proven deeply infiltrating endometriosis (DIE). METHODS: This was a retrospective study of a continuous series of 81 patients presenting histologically proven DIE who underwent preoperative investigations using both REU and MRI. The sonographer and the radiologist, who were unaware of the clinical findings and patient history, but knew that DIE was suspected, were asked whether there was involvement of the digestive wall. RESULTS: Rectal DIE was confirmed histologically in 34 of the 81 (42%) patients. For the diagnosis of rectal involvement, sensitivity, specificity and positive and negative predictive value for REU were 97.1%, 89.4%, 86.8% and 97.7% and for MRI they were 76.5%, 97.9%, 96.3% and 85.2%. CONCLUSION: The sensitivity and negative predictive value of REU were higher than those of MRI suggesting that REU performs better than MRI in the diagnosis of rectal involvement for patients presenting with DIE. Prospective studies with a large number of patients are needed in order to validate these preliminary results.

Adult↗

[Deep pelvic endometriosis: management and proposal for a "surgical classification"].

Deep pelvic endometriosis presents essentially in the form of a painful syndrome dominated by deep dyspareunia and painful functional symptoms that recur according to the menstrual cycle, with the semiology directly correlated with the location of the lesions (bladder, rectum). It is essential to investigate these deep endometriosis lesions and draw up a precise map, which is the only way to be sure that exeresis will be complete. The treatment of first intention remains surgery, and medical treatment is only palliative in the majority of cases. Success of treatment depends on how radical surgical exeresis is. Based on analysis of the anatomical distribution of deep pelvic endometriosis lesions, a "surgical classification" is proposed with the aim of establishing standard modes for surgical treatment. Further studies are required to clarify the place and modes for pre- and postoperative medical treatment.

Adnexal Diseases↗

Fatty acid oxidation in African-American and Caucasian women during physical activity.

The goal of this study was to determine whether differences in physical activity-related fat oxidation exist between lean and obese African-American (LAA and OAA) and lean and obese Caucasian (LC and OC) premenopausal women. Lean AA (28.4 +/- 2.8 yr, n = 7), LC (24.7 +/- 1.8 yr, n = 9), OAA (30.9 +/- 2.2 yr, n = 11), and OC (34.1 +/- 2.5 yr, n = 9) women underwent preliminary assessment of peak aerobic capacity (VO2 peak). On a subsequent testing day, participants exercised after an 8-h fast on a cycle ergometer at 15 W (approximately 40% VO2 peak) for 10 min and then for 10 min at approximately 65% VO2 peak). Fatty acid oxidation was determined using the average respiratory exchange ratio and O2 consumption during minutes 5-9 of the exercise session. Percent body fat and fat-free mass were lower (P < 0.05) in LAA (25.8 +/- 2.8% and 48.3 kg) and LC (26.4 +/- 2.0% and 45.8 +/- 1.7 kg) than in OAA (41.2 +/- 1.3% and 58.8 +/- 3.3 kg) and OC (39.3 +/- 2.7% and 58.6 kg) women. Fat oxidation among the groups was analyzed statistically using analysis of covariance with fat-free mass and VO2 peak) as covariates. During exercise at 15 W, fat oxidation was as low in LAA (0.134 +/- 0.024 g/min) as in OAA (0.144 +/- 0.026 g/min) and OC (0.156 +/- 0.020 g/min) women: all these rates of fat oxidation were lower than in LC women (0.200 +/- 0.021 g/min, P < 0.05, LC vs. all other groups). Fatty acid oxidation during higher-intensity exercise (65% VO2 peak)) was higher in LC than in OC women but was not statistically different between African-American and Caucasian groups. Fatty acid oxidation was therefore lower during low-intensity physical activity in OAA, LAA, and OC than in LC women.

Adult↗

Role of female sex steroids in regulating cholesteryl ester transfer protein in transgenic mice.

The role of sex steroids in the regulation of cholesteryl ester transfer protein (CETP) was examined in the following groups of female transgenic mice carrying the human CETP gene: (1) normal, (2) ovariectomized, (3) ovariectomized and treated with estrogen; (4) ovariectomized and treated with progesterone; (5) ovariectomized and treated with both hormones, and (6) ovariectomized and treated with tamoxifen. CETP activity was measured in the plasma, and in the particulate and the soluble fractions of liver, muscle, and adipose tissue. Human CETP specific activity was determined by taking the difference of cholesterol ester transfer in the presence and absence of an antibody (TP2) against human CETP Ovariectomy reduced hormone levels, but did not completely abolish them from the circulation. Plasma CETP activity was significantly reduced in the tamoxifen group. There were significant reductions in CETP in liver homogenate and the soluble fraction, as well as in the particulate fraction of adipose with ovariectomy. Hormone replacement did not restore CETP activity in either the plasma or the tissues. Tamoxifin treatment resulted in a decrease in CETP activity in both fractions of liver, but had no effect on adipose. In the soluble fraction of adipose tissue and both fractions of muscle, only trace CETP activity was detected. We conclude that (1) minimal amounts of sex steroid hormones may be sufficient to affect CETP expression; (2) the effects of sex steroid hormones vary among tissues; and (3) in addition to the sex steroids, factor(s) from the ovary are needed for the full expression of CETP in this animal model.

Animals↗

Effects of oral combined hormone replacement therapy on plasma lipids and lipoproteins.

Hormone replacement therapy has been shown to decrease the risk of coronary heart disease (CHD) in menopausal women. In this cross-sectional study, we addressed the following question: What effects would combined oral hormone replacement therapy have on plasma lipid and lipoprotein profiles independent of the other known CHD risk factors? We analyzed the plasma lipoproteins of two groups of menopausal women who were randomly selected from a large database of individuals. One group (n = 10) was not taking any hormone replacement therapy (NO HRT), while the second group (n = 8) was taking a daily dose of 0.625 mg conjugated estrogen and 2.5 mg medroxyprogesterone orally (PremPro, Wyeth-Ayerst, Philadelphia, PA) for at least 6 months (HRT). The two groups were not different in age, body weight, percent body fat, body mass index (BMI), waist to hip ratio, blood pressure, or insulin and glucose levels. High-density lipoprotein (HDL)-cholesterol was significantly higher (P < .05) in the HRT group. The total cholesterol (TC) to HDL-cholesterol ratio was significantly lower for HRT versus NO HRT (P < .05). Apolipoprotein (apo) A-1, the apo A-1/B ratio, and lecithin:cholesterol acyltransferase (LCAT) activity were significantly higher in HRT (P < .05). Lipoprotein subclass profiles measured by nuclear magnetic resonance (NMR) spectroscopy showed an increase in larger HDL subpopulations (H3 and H4) in HRT (P < .05), which are considered antiatherogenic. No differences were seen in the cholesterol concentration or size of low-density lipoprotein (LDL) subpopulations in HRT compared with NO HRT. These results indicate that the combined estrogen and progesterone treatment leads to beneficial effects on plasma lipoproteins. The beneficial effects include (1) increases in HDL-cholesterol and predominance of HDL2, (2) no adverse effects on LDL subpopulation distribution, and (3) increases in apo A-1 levels and LCAT activity, which indicate an improvement in reverse cholesterol transport.

Administration, Oral↗

Lipid and lipoprotein responses to oral combined hormone replacement therapy in normolipemic obese women with controlled type 2 diabetes mellitus.

This study investigated the effects of oral combined hormone replacement therapy (OCHRT) on lipid concentrations and subpopulation distribution of lipoproteins in nine postmenopausal women with type 2 diabetes mellitus and moderate glycemic control. After 16 weeks of continuous daily therapy of conjugated estrogens 0.625 mg and medroxyprogesterone 2.5 mg, the mean concentration of high-density lipoprotein (HDL) cholesterol showed a statistically significant increase of 16.7%, predominantly in the HDL2 subfraction. No statistically significant changes in mean concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, very low-density lipoprotein (VLDL) triglycerides, apolipoprotein A1, or apolipoprotein B were evident. Likewise, no changes were found in the average diameter of VLDL, LDL, or HDL particles; triglyceride concentrations of VLDL subfractions; cholesterol concentrations of LDL subfractions; or chemical composition of plasma LDL. These findings lend further support to the use of OCHRT in postmenopausal women with diabetes to decrease their risk for coronary artery disease.

Administration, Oral↗

Mouse monoclonal antipeptide antibodies specific for cholesteryl ester transfer protein (CETP).

A synthetic peptide whose amino acid sequence corresponds to residues 131-142 of human cholesteryl ester transfer protein (CETP) was used as an immunogen to generate a panel of monoclonal antibodies (MAbs) specific for the intact CETP molecule. Spleen cells from BALB/c mice immunized with the peptide conjugated with keyhole limpet hemocyanin (KLH) were fused with SP2/0 myeloma cells. Two MAbs that bound fixed peptide in an enzyme-linked immunoabsorbent assay (ELISA) were partially characterized regarding their specificity and biological activity. ATM192 of the IgG1 subclass and J16-14 of the IgG3 subclass were used in a Western blot assay as well as in the ELISA. We have also shown through the use of immunoprecipitation that ATM192 can remove CETP enzyme activity from human serum without destroying the enzyme's activity. We have also shown that the antibodies can bind CETP from rabbits. The specificity studies and the lack of inhibition of enzymatic activity suggest that the MAbs bind a structural area of the CETP molecule not a part of the active binding site of the enzyme. We conclude that these antibodies can be valuable as tools for studying CETP levels in human serum as well as in tissue homogenates from rabbits and humans.

Animals↗

Effect of oral magnesium supplementation on selected cardiovascular risk factors in non-insulin-dependent diabetics.

OBJECTIVE: To evaluate the impact of oral magnesium supplementation on risk factors for end-organ disease in patients with non-insulin-dependent diabetes mellitus (NIDDM). DESIGN: A 16-week randomized, double-blind, placebo-controlled crossover trial. SETTING: Outpatient center of an academic family medicine residency program. PATIENTS: Twenty-eight patients (age range, 28 to 84 years; 57.1% black; 85.7% women) with NIDDM controlled by diet and/or an oral hypoglycemic, with a serum cholesterol levels over 5.20 mmol/L (200 mg/dL). INTERVENTION: Following a 2-week placebo run-in period, each patient was randomized to receive either sustained-release magnesium chloride (Slo-Mag), 384 mg/d, or an identical-appearing placebo for 6 weeks. After a 2-week interim washout period, each patient was then treated with the alternative regimen for an additional 6-week period. MAIN OUTCOME MEASURES: The systolic and diastolic blood pressure and levels of serum glucose, low-density and high-density lipoprotein and total cholesterol, triglycerides, and serum and total erythrocyte magnesium were measured at the beginning, midpoint, and end of each 6-week treatment phase. RESULTS: Systolic blood pressure fell an average of 7.4 mm Hg (P < .05) with treatment. There was no significant change in diastolic blood pressure or levels of serum glucose, low-density and high-density lipoprotein and total cholesterol, triglycerides, or serum and erythrocyte magnesium. CONCLUSIONS: Oral magnesium supplementation in the doses and duration studied is modestly effective in reducing systolic blood pressure in patients with NIDDM but has little impact on other important biochemical parameters related to diabetes-associated end-organ disease.

Administration, Oral↗

A nuclear factor required for specific translation of cyclin B may control the timing of first meiotic cleavage in starfish oocytes.

In most animals, the rate of cyclin B synthesis increases after nuclear envelope breakdown during the first meiotic cell cycle. We have found that cyclin B-cdc2 kinase activity drops earlier in emetine-treated than in control starfish oocytes, although the protein synthesis inhibitor does not activate the cyclin degradation pathway prematurely. Moreover, protein synthesis is required to prevent meiotic cleavage to occur prematurely, sometimes before chromosomes have segregated on the metaphase plate. In normal conditions, increased synthesis of cyclin B after germinal vesicle breakdown (GVBD) balances cyclin degradation and increases the time required for cyclin B-cdc2 kinase to drop below the level that inhibits cleavage. Taken together, these results point to cyclin B as a possible candidate that could explain the need for increased protein synthesis during meiosis I. Although direct experimental evidence was not provided in the present work, cyclin B synthesis after GVBD may be important for correct segregation of homologous chromosomes at the end of first meiotic metaphase, as shown by a variety of cytological disorders that accompany premature cleavage. Although the overall stimulation of protein synthesis because of cdc2 kinase activation is still observed in oocytes from which the germinal vesicle has been removed before hormonal stimulation, the main increase of cyclin B synthesis normally observed after germinal vesicle breakdown is suppressed. The nuclear factor required for specific translation of cyclin B after GVBD is not cyclin B mRNA, as shown by using a highly sensitive reverse transcription followed by polymerase chain reaction procedure that failed to detect any cyclin B mRNA in isolated germinal vesicles.

Anaphase↗

Okadaic acid mimics a nuclear component required for cyclin B-cdc2 kinase microinjection to drive starfish oocytes into M phase.

G2-arrested oocytes contain cdc2 kinase as an inactive cyclin B-cdc2 complex. When a small amount of highly purified and active cdc2 kinase, prepared from starfish oocytes at first meiotic metaphase, is microinjected into Xenopus oocytes, it induces activation of the inactive endogenous complex and, as a consequence, drives the recipient oocytes into M phase. In contrast, the microinjected kinase undergoes rapid inactivation in starfish oocytes, which remain arrested at G2. Endogenous cdc2 kinase becomes activated in both nucleated and enucleated starfish oocytes injected with cytoplasm taken from maturing oocytes at the time of nuclear envelope breakdown, but only cytoplasm taken from nucleated oocytes becomes able thereafter to release second recipient oocytes from G2 arrest, and thus contains M phase-promoting factor (MPF) activity. Both nucleated and enucleated starfish oocytes produce MPF activity when type 2A phosphatase is blocked by okadaic acid. If type 2A phosphatase is only partially inhibited, neither nucleated nor enucleated oocytes produce MPF activity, although both do so if purified cdc2 kinase is subsequently injected as a primer to activate the endogenous kinase. The nucleus of starfish oocytes contains an inhibitor of type 2A phosphatase, but neither active nor inactive cdc2 kinase. Microinjection of the content of a nucleus into the cytoplasm of G2-arrested starfish oocytes activates endogenous cdc2 kinase, produces MPF activity, and drives the recipient oocytes into M phase. Together, these results show that the MPF amplification loop is controlled, both positively and negatively, by cdc2 kinase and type 2A phosphatase, respectively. Activation of the MPF amplification loop in starfish requires a nuclear component to inhibit type 2A phosphatase in cytoplasm.

Animals↗

Low density lipoprotein interaction with artery derived proteoglycan: the influence of LDL particle size and the relationship to atherosclerosis susceptibility.

An in vitro binding system was used to determine whether increases in LDL particle size and altered LDL chemical composition accompanying increased plasma cholesterol concentrations result in greater association of LDL with artery proteoglycan (PG) and whether the binding is related to atherosclerosis. LDL isolated from hypercholesterolemic atherosclerosis-susceptible White Carneau and resistant Show Racer pigeons was complexed to purified White Carneau pigeon aorta-derived high molecular weight PG under conditions whereby PG monomers were saturated. Using LDL of molecular weight greater than 5.0 x 10(6) daltons from both pigeon breeds, an inverse correlation between LDL size and the number of LDL particles bound per micrograms PG was demonstrated (r = 0.87, P less than 0.01). This relationship was attributed to the increased size of the LDL particle rather than any modification in chemical composition known to occur when LDL size increases, suggesting the major effect was attributed to steric hindrance. White Carneau pigeons with high molecular weight LDL had more severe atherosclerosis and the PG-LDL complexes contained excess cholesterol but no relationship was seen between atherosclerosis and number of LDL complexed. In animals with LDL between 3.6 x 10(6) and 4.8 x 10(6) daltons, considerable variability in PG binding was apparent, but this also was not related to LDL chemical composition. In this group of pigeons, which were all White Carneau, the positive relationship of PG-LDL binding and aorta cholesterol concentration was significant (r = 0.67, P less than 0.05). These results suggest that factors other than chemical composition (perhaps surface charge or apoprotein conformation changes) influence PG-LDL binding and that the assessment of PG-LDL binding is useful in predicting atherosclerosis in animals that do not respond to hypercholesterolemia by increasing LDL size.

Animals↗

Response of lipogenesis and fatty acid synthetase to physical training and exhaustive exercise in rats.

The effect of physical training and exhaustive exercise on fatty acid synthesis in rat liver and adipose tissue has been investigated. Exercise training (treadmill running) significantly (p less than 0.05) decreased body wt, eipdidymal fat pad wt, adipocyte size, and hepatic fatty acid synthetase activity. Training did not significantly affect adipose tissue cell number, lipogenesis from glucose-U-14C, or fatty acid synthetase. Exercise to exhaustion immediately prior to sacrifice significantly (p less than 0.05) decreased lipogenesis from glucose-U-14C and fatty acid synthetase in adipose tissue from trained but not untrained rats. Liver fatty acid synthetase was not significantly influenced by exhaustive exercise. The results of this study indicate that rats may adapt to physical training by decreasing adipose tissue lipogenesis during exhaustive exercise. This adaptation in energy metabolism may facilitate physically trained animals in conserving blood glucose during exhaustive exercise, thereby prolonging endurance.

Adipose Tissue↗