Tissue damage variables: energy source and operator.
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Biomedical subjects
Publications and source records attributed to A A Luciano.
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OBJECTIVE: To determine the effects of estrone sulfate alone or with different doses of medroxyprogesterone acetate on serum lipid and lipoprotein levels. METHODS: A multicenter, double-masked, randomized trial for 1 year involved 682 postmenopausal women, aged 53.8 +/- 0.2 years (mean +/- standard deviation) with intact uteri. Subjects received fixed daily doses of 0.625 mg of estrone sulfate and one of the following regimens: placebo; 2.5 mg daily of medroxyprogesterone acetate; 5 mg daily of medroxyprogesterone acetate; or 10 mg of medroxyprogesterone acetate for the first 12 days of each 28-day cycle. Fasting lipid and lipoprotein levels were measured at baseline and weeks 12, 16, 24, 30, 36, and 52 of treatment. Absolute mean changes from baseline were determined by paired t test, and treatment effects were determined by analysis of variance. RESULTS: Total cholesterol levels decreased significantly (P <.05) from baseline in all study groups; however, reduction was significantly greater (P <.001) in the 2.5-, 5-, and 10-mg groups (-13.3%, -15.2%, and -14.1%) than in the placebo group (-4.9%). Low-density lipoprotein cholesterol levels decreased significantly and equally in all groups (-10.1% to -12.3%). High-density lipoprotein cholesterol levels increased by 3.2% with unopposed estrogen (P <.05) and did not change from baseline with combined therapy. Triglyceride and very low-density lipoprotein cholesterol levels increased by 13.4% and 2.7%, respectively, in the placebo group, did not change in the 2.5-mg group, decreased by 10.2% and 2.0% and by 11.4% and 2.2% in the 5- and 10-mg groups, respectively (P <.05). CONCLUSION: Estrone sulfate at the daily dose of 0.625 mg alone or with medroxyprogesterone acetate significantly improved lipoprotein levels. Combined therapy with medroxyprogesterone acetate and estrone sulfate was associated with statistically significantly greater reduction in total cholesterol and statistically significantly less increase in triglyceride levels than unopposed estrone sulfate therapy.
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STUDY OBJECTIVE: To evaluate and compare the safety and efficacy of a new method to enter the abdominal cavity at laparoscopy. DESIGN: (Canadian Task Force classification II-2). SETTING: Referral center for reproductive surgery in a teaching hospital affiliated with a university-based residency program. PATIENTS: Twenty representative women of variable body habitus (body mass index 16.5-39 kg/m2). INTERVENTION: Laparoscopy and laparotomy. MEASUREMENTS AND MAIN RESULTS: We measured the thickness of the abdominal wall at the base of the umbilicus and just below its inferior border. We also measured distances traversed by the Veress needle or cannula from skin to peritoneal cavity at both sites when the piercing instrument was directed at 45- or 90-degree angle from the horizontal plane of the abdominal wall. Finally, we measured distances created between parietal peritoneum and underlying viscera when the abdominal wall was lifted manually or with towel clips placed laterally, 2 cm from the umbilicus and at the edges of the intraumbilical incision. Distances created between parietal peritoneum and underlying viscera while lifting the abdominal wall by each of these three techniques were measured with a calibrated probe inserted through the intraumbilical port and observed with a 5-mm laparoscope from the suprapubic port. These distances were measured before and after carbon dioxide insufflation at 15 mm Hg, as well as before and while inserting the cannula through the abdominal wall. Mean +/- SD thickness of the abdominal wall at the base of the umbilicus and lower border of the umbilicus were 1.4 +/- 0.5 and 3.0 +/- 1.1 cm, respectively (p <0.01). Distances traversed by piercing instruments through the abdominal wall at the umbilicus and lower border of the umbilicus when the angle of insertion was 45 degrees were 1.98 +/- 0.76 and 4.24 +/- 1.53 cm, respectively (p <0.01). Distances were significantly greater when the angle of insertion was 45 degrees rather than 90 degrees. Distances between parietal peritoneum and underlying viscera when the abdominal wall was lifted manually with towel clips 2 cm from the umbilicus, or at the edges of the intraumbilical incision were 3.5 +/-1.14, 5.14 +/- 1.04, and 6.8 +/- 0.94 cm, respectively (p <0.01). When force was applied on the abdomen at cannula insertion, these distances were reduced by 2.1 +/- 0.91, 1.03 +/- 0.32, and zero centimeters, respectively (p <0.01). CONCLUSION: Our technique of inserting the cannula perpendicularly through the base of the umbilicus traverses the shortest distance to the abdominal cavity through the least vascular area of the abdominal wall. Lifting the abdominal wall with towel clips placed at the edges of the intraumbilical incision achieves the greatest distance between parietal peritoneum of the abdominal wall and underlying viscera, thus maximizing the margin of safety in protecting peritoneal organs and retroperitoneal vessels from injury.
During the past 25 years, the incidence of ectopic pregnancy has progressively increased while the morbidity and mortality have substantially decreased, and the treatment has progressed from salpingectomy by laparotomy to conservative surgery by laparoscopy and more recently to medical therapy. This therapeutic transition from surgical emergency to medical management has been attributed to early diagnosis through the use of sensitive assays for hCG and the high definition of vaginal ultrasound. By using these sensitive diagnostic tools, we are now able to select those patients who are most likely to respond to medical management versus those who are at high risk of rupture and require surgery. Besides being less invasive and associated with significantly lower risks, medical therapy with methotrexate results in significant cost savings, which have been calculated to be approximately $3,000 per treated patient. Our goal is to identify those patients with ectopic pregnancy who are most likely to respond to methotrexate therapy and least likely to develop significant side effects. Recent studies have helped us define the predictors of success with methotrexate treatment in women with ectopic pregnancy. The reported success rates of treating ectopic pregnancy with methotrexate vary from 71% to 100%. The highest success rates have been reported from institutions that have detailed diagnostic and therapeutic protocols, readily available assays for serum hCG levels, high-resolution vaginal probe ultrasound, and support staff that can closely monitor clinical response. The importance of developing specific protocols to create a clinical environment that supports the effective use of medical therapy for ectopic pregnancy is confirmed by the associated cost savings, decreased morbidity, and patient preference. Modern diagnostic advances and minimally invasive treatments coupled with improved success rates for assisted reproductive technologies should reduce the morbidity and mortality associated with ectopic pregnancy and offer the affected couple a much more optimistic outlook for subsequent reproductive potential.
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Interstitial pregnancy is a rare and potentially dangerous event. Standard treatment involves laparotomy with cornual resection or hysterectomy, with few reported cases of laparoscopic management. A 14-week, 6-cm interstitial pregnancy was treated laparoscopically, without cornual resection or hysterectomy. Gestational products were removed from the fetal side of the implantation site through a salpingotomy incision through myometrium. In selected patients, this procedure can be accomplished safely and efficaciously while preserving reproductive function and avoiding laparotomy.
We have previously shown that more prominent immune responses are induced to antigens expressed from multicopy plasmids in live attenuated vaccine vector strains of Vibrio cholerae than to antigens expressed from single-copy genes on the V. cholerae chromosome. Here, we report the construction of a DeltaglnA derivative of V. cholerae vaccine strain Peru2. This mutant strain, Peru2DeltaglnA, is unable to grow on medium that does not contain glutamine; this growth deficiency is complemented by pKEK71-NotI, a plasmid containing a complete copy of the Salmonella typhimurium glnA gene, or by pTIC5, a derivative of pKEK71-NotI containing a 1. 8-kbp fragment that directs expression of CtxB with a 12-amino-acid epitope of the serine-rich Entamoeba histolytica protein fused to the amino terminus. Strain Peru2DeltaglnA(pTIC5) produced 10-fold more SREHP-12-CtxB in supernatants than did ETR3, a Peru2-derivative strain containing the same fragment inserted on the chromosome. To assess immune responses to antigens expressed by this balanced lethal system in vivo, we inoculated germfree mice on days 0, 14, 28, and 42 with Peru2DeltaglnA, Peru2DeltaglnA(pKEK71-NotI), Peru2(pTIC5), Peru2DeltaglnA(pTIC5), or ETR3. All V. cholerae strains were recoverable from stool for 8 to 12 days after primary inoculation, including Peru2DeltaglnA; strains containing plasmids continued to harbor pKEK71-NotI or pTIC5 for 8 to 10 days after primary inoculation. Animals were sacrificed on day 56, and serum, stool and biliary samples were analyzed for immune responses. Vibriocidal antibody responses, reflective of in vivo colonization, were equivalent in all groups of animals. However, specific anti-CtxB immune responses in serum (P </= 0.05) and bile (P </= 0. 001) were significantly higher in animals that received Peru2DeltaglnA(pTIC5) than in those that received ETR3, confirming the advantage of higher-level antigen expression in vivo. The development of this balanced lethal system thus permits construction and maintenance of vaccine and vector strains of V. cholerae that express high levels of immunogenic antigens from plasmid vectors without the need for antibiotic selection pressure.
Prolactin is a polypeptide hormone essential for lactation. Its production in the lactotroph cells of the anterior pituitary is regulated primarily by the inhibitory action of hypothalamic dopamine. Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis, occurring mostly in women and presenting most commonly with amenorrhea and galactorrhea. Causes of hyperprolactinemia include physiologic, pharmacologic and pathologic factors; pituitary adenoma is a common pathologic cause. Women may present with decreased libido, infertility, oligomenorrhea/amenorrhea and galactorrhea. Men may present with decreased libido, infertility, gynecomastia or impotence. In the absence of an identifiable and treatable underlying cause, hyperprolactinemia is generally treated with dopamine agonist medications.
OBJECTIVE: To determine whether low-level 45,X/46,XX mosaicism may be present in some women with premature ovarian failure (POF). DESIGN: Slide preparations were made from lymphocyte cultures stimulated with phytohemagglutinin, and fluorescence in situ hybridization (FISH) was then performed using a biotin-labeled X-chromosome probe. SETTING: Cytogenetics laboratory. PATIENT(S): Fifteen women with idiopathic POF, 20 age-matched controls, and an additional 10 older control women with normal reproductive histories. INTERVENTION(S): Blood samples were collected. MAIN OUTCOME MEASURE(S): The number of X chromosomes present in each cell. RESULT(S): In patients with POF, the percentage of cells with a single X chromosome (mean, 5.50) was significantly greater than in the controls of similar age (mean, 2.42). For control subjects, there appeared to be a linear correlation between the number of cells with a single X chromosome and age. CONCLUSION(S): Some cases of POF may be attributable to low-level 45,X/46,XX mosaicism, which can be detected using FISH. In the lymphocytes from normal women, the rate of accumulation of cells with a single X chromosome was approximately 700 per 10(6) cells per year.
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The purposes of this investigation were to evaluate the characteristics of three consecutive menstrual cycles and to determine the frequency ofluteal phase deficiency (LPD) and anovulation in a sample of sedentary and moderately exercising, regularly menstruating women. For three consecutive menstrual cycles, subjects collected daily urine samples for analysis of FSH, estrone conjugates (E1C), pregnanediol-3-glucuronide (PdG), and creatinine (Cr). Sedentary (n=11) and exercising (n=24) groups were similar in age (27.0+/-1.3 yr), weight (60.3+/-3.1 kg), gynecological age (13.8+/-1.2 yr), and menstrual cycle length (28.3+/-0.8 days). Menstrual cycles were classified by endocrine data as ovulatory, LPD, or anovulatory. No sedentary women (0%) had inconsistent menstrual cycle classifications from cycle to cycle, but 46% of the exercising women were inconsistent. The sample prevalence of LPD in the exercising women was 48%, and the 3-month sample incidence was 79%. In the sedentary women, 90% of all menstrual cycles were ovulatory (SedOvul; n=28), whereas in the exercising women only 45% were ovulatory (ExOvul; n=30); 43% were LPD (ExLPD; n=28), and 12% were anovulatory (ExAnov; n=8). In ExLPD cycles, the follicular phase was significantly longer (17.9+/-0.7 days), and the luteal phase was significantly shorter (8.2+/-0.5 days) compared to ExOvul (14.8+/-0.9 and 12.9+/-0.3 days) and SedOvul (15.9+/-0.6 and 12.9+/-0.4 days) cycles. Luteal phase PdG excretion was lower (P < 0.001) in ExLPD (2.9+/-0.3 microg/mg Cr) and ExAnov (0.8+/-0.1 microg/mg Cr) cycles compared to SedOvul cycles (5.0+/-0.4 microg/mg Cr). ExOvul cycles also had less (P < 0.01) PdG excretion during the luteal phase (3.7+/-0.3 microg/mg Cr) than the SedOvul cycles. E1C excretion during follicular phase days 2-5 was lower (P=0.05) in ExOvul, ExLPD, and ExAnov cycles compared to SedOvul cycles and remained lower (P < 0.02) in the ExLPD and ExAnov cycles during days 6-12. The elevation in FSH during the luteal-follicular transition was lower (P < 0.007) in ExLPD (0.7+/-0.1 ng/mg Cr) cycles compared to SedOvul and ExOvul cycles (1.0+/-0.1 and 1.1+/-0.1 ng/mg Cr, respectively). Energy balance and energy availability were lower (P < 0.05) in ExAnov cycles than in other menstrual cycle categories. The blunted elevation in FSH during the luteal-follicular transition in exercising women with LPD may explain their lower follicular estradiol levels. These alterations in FSH may act in concert with disrupted LH pulsatility as a primary and proximate factor in the high frequency of luteal phase and ovulatory disturbances in regularly menstruating, exercising women.
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The primary purpose of this study was to determine whether decreased ovarian progesterone production, associated with short and inadequate luteal phases in exercising women, was associated with decreased bone mineral density (BMD) and altered bone metabolism. Thirty-three eumenorrheic menstruating women participated in this study for 3 months. Subjects were required to collect daily urine samples for three consecutive menstrual cycles and have blood and urine collected weekly. Daily urine samples were analyzed for free LH, estrone conjugates (E1C), and pregnanediol 3-glucuronide (PdG), adjusted for creatinine, whereas weekly blood and urine samples were analyzed for bone markers, estradiol, progesterone, FSH, and LH. Based on the analyses of these samples, subjects were divided into three groups: sedentary ovulatory (SedOvul; n = 9), exercising ovulatory (ExOvul; n = 14), and exercising luteal phase defects (ExLPD; n = 10). The three groups were matched for age (27.6 +/- 1.0 yr), weight (60.6 +/- 1.9 cm), and reproductive maturity (14.5 +/- 1.0 yr), PdG production during the luteal phase was lower (P = 0.004) in the ExLPD women compared to that in the SedOvul group (2.4 +/- 0.4 vs. 5.1 +/- 0.6 ng/mL creatinine, respectively). The ExOvul group also had less (P < 0.01) PdG production during the luteal phase (3.5 +/- 0.3 ng/mL creatinine) compared to the SedOvul group. The total production of PdG, as assessed by area under the curve analysis, was also lower (P < 0.001) in the ExOvul and ExLPD groups compared to that in the SedOvul group. E1C production, however, was not different (P > 0.05) among the groups, except for E1C during the early follicular phase, which was lower (P = 0.043) in the ExLPD group than that in the SedOvul group. BMD and biochemical markers of bone metabolism were unaffected by and not associated with the compromised progesterone environment, but BMD values at the proximal femur (r = 0.354; P = 0.061) and total body (r = 0.359; P = 0.056) were associated with decreased early follicular E1C production. We conclude the following. 1) Luteal phase disturbances occur independent of training volume, and volume of training does not have to be severe to result in menstrual disturbances. 2) As a result of exercise, disturbance in progesterone production is not associated with decreased bone mass. 3) Long follicular phases are associated with reduced estrogen production during the early follicular phase, which are both associated with decreased bone mass. 4) Provided the estradiol status is adequately maintained, BMD is unaffected by decreased progesterone production associated with short and inadequte luteal phases in exercising women.
OBJECTIVES: To evaluate the efficacy of a commonly used progestogen, medroxyprogesterone acetate (MPA), in the prevention of postoperative adhesion formation. DESIGN: A double-blind, controlled study evaluated the efficacy of MPA to reduce postoperative adhesion formation and compared it with other adjuvants and controls in a rat model. SETTING: Animal Care Facility of an academic research setting. SUBJECTS: Seventy-five Sprague-Dawley female rats randomly divided into five groups. INTERVENTIONS: Three weeks before surgery, the animals from each group were administered an IM injection of one of the following regimens: [1] 15 mg MPA; [2] both 15 mg MPA and 0.75 mg leuprolide acetate (LA); [3] 0.75 LA; or [4] and [5] comparable volumes of sterile saline. A standardized surgical trauma was inflicted in all animals. Before abdominal closure, 2 mL of Ringer's Lactate was instilled in the abdominal cavity of all groups except group 5 (controls). Three weeks after surgery, the rats were killed and the adhesions were scored on a scale of 0 to 3 according to their size, thickness, and vascularity. MAIN OUTCOME MEASURE: Postoperative adhesions. RESULTS: The preoperative administration of MPA resulted in the least number and the least severe adhesions. The combination of LA and MPA did not reduce postoperative adhesion formation. Both Ringer's Lactate and LA reduced postoperative adhesions but not to the same extent as MPA. CONCLUSION: The preoperative administration of MPA in our laboratory animal model results in the most significant reduction of postoperative adhesion formation. This action of MPA may be mediated by the induction of both a progestational and a hypoestrogenemic milieu. However, the ultimate role of MPA in a clinical situation requires further investigation.