Search

Background: Pelvic organ prolapse is common and is strongly associated with childbirth and increasing age. Women with prolapse are often advised to do pelvic floor muscle exercises, but evidence supporting the benefits of such exercises is scarce. We aimed to establish the effectiveness of one-to-one individualised pelvic floor muscle training for reducing prolapse symptoms., Methods: We did a parallel-group, multicentre, randomised controlled trial at 23 centres in the UK, one in New Zealand, and one in Australia, between June 22, 2007, and April 9, 2010. Female outpatients with newly-diagnosed, symptomatic stage I, II, or III prolapse were randomly assigned (1:1), by remote computer allocation with minimsation, to receive an individualised programme of pelvic floor muscle training or a prolapse lifestyle advice leaflet and no muscle training (control group). Outcome assessors, and investigators who were gynaecologists at trial sites, were masked to group allocation; the statistician was masked until after data analysis. Our primary endpoint was participants' self-report of prolapse symptoms at 12 months. Analysis was by intention-to-treat analysis. This trial is registered, number ISRCTN35911035., Findings: 447 eligible patients were randomised to the intervention group (n=225) or the control group (n=222). 377 (84%) participants completed follow-up for questionnaires at 6 months and 295 (66%) for questionnaires at 12 months. Women in the intervention group reported fewer prolapse symptoms (ie, a significantly greater reduction in the pelvic organ prolapse symptom score [POP-SS]) at 12 months than those in the control group (mean reduction in POP-SS from baseline 3.77 [SD 5.62] vs 2.09 [5.39]; adjusted difference 1.52, 95% CI 0.46-2.59; p=0.0053). Findings were robust to missing data. Eight adverse events (six vaginal symptoms, one case of back pain, and one case of abdominal pain) and one unexpected serious adverse event, all in women from the intervention group, were regarded as unrelated to the intervention or to participation in the study., Interpretation: One-to-one pelvic floor muscle training for prolapse is effective for improvement of prolapse symptoms. Long-term benefits should be investigated, as should the effects in specific subgroups., Funding: Chief Scientist Office of the Scottish Government Health and Social Care Directorates, New Zealand Lottery Board, and National Health and Medical Research Council (Australia)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: This is a review of a series of patients who presented with thymoma over the most recent 20-year period. Changes and trends in disease patterns were documented., Methods: Data were collated retrospectively but all pathology slides were reviewed. Survival functions were estimated using the Kaplan-Meier method., Results: Seventy-one patients had a partial or total thymectomy during this period for a thymoma. Average age was 55 years. Twenty-three patients (32%) had myaesthenia gravis. Eighteen patients (25%) were asymptomatic. Thirty-three patients (47%) had stage 1 disease. Complete resection was achieved in 60 patients (85%). Five-year survival was 88%. Fifty percent of patients with myesthenia gravis showed improvement in symptoms., Conclusions: Five- and 10-year survival rates in this study are better than in other series. We attribute this to an increasing number of patients with stage 1 and stage 2 disease, particularly those with myasthenia gravis who now have screening computer tomography, and also to the surgical intent of aiming to achieve complete resection even if excision of adjacent tissue is required.

Objective: The purpose of this study was to identify the placental expression of adrenomedullin and adrenomedullin receptor messenger ribonucleic acid and compare them between placentas from pregnancies associated with oligohydramnios as a result of uteroplacental insufficiency and placentas from normal pregnancies., Study Design: Total ribonucleic acid was extracted from the amnion, chorion, cotyledon, umbilical vein, and umbilical artery in 5 normal placentas and 3 placentas from pregnancies complicated by oligohydramnios. A cell line known to express messenger ribonucleic acid of adrenomedullin and its receptor was used to optimize the polymerase chain reaction and served as a positive control preparation in all experiments. Semiquantitative reverse transcriptase-polymerase chain reaction results for adrenomedullin and adrenomedullin receptor were compared between tissues as densitometric ratios of adrenomedullin or adrenomedullin receptor messenger ribonucleic acid to beta(2)-microglobulin messenger ribonucleic acid. Results were analyzed with a Kruskal-Wallis 1-way analysis of variance. Immunohistochemical staining with an antibody to human adrenomedullin was used to localize adrenomedullin in all tissue types., Results: Messenger ribonucleic acid sequences for adrenomedullin and adrenomedullin receptor genes were identified in all tested placental tissue components. Within the normal placentas the expressions of adrenomedullin and adrenomedullin receptor messenger ribonucleic acid sequences did not differ statistically between the tissue components. Within placentas from patients with oligohydramnios the expressions of adrenomedullin and adrenomedullin receptor messenger ribonucleic acid did not differ statistically between the tissue components. When normal placentas were compared with placentas from pregnancies complicated by oligohydramnios, however, a 5-fold increase in adrenomedullin messenger ribonucleic acid and a 3-fold increase in adrenomedullin receptor messenger ribonucleic acid were seen in placentas from patients with oligohydramnios. Adrenomedullin immunoreactivity was present in all tissues studied., Conclusion: The expression of messenger ribonucleic acid for both adrenomedullin and its receptor in these tissue components implies that placental tissues function in both synthesis and action of adrenomedullin. The increased adrenomedullin messenger ribonucleic acid expression in the umbilical artery and the elevated adrenomedullin receptor messenger ribonucleic acid expression in the cotyledons of placentas from patients with oligohydramnios may represent a local fetoplacental physiologic adaptive response to vascular compromise.

Objective: The study's objective was to determine whether there is a difference in the plasma concentration of adrenomedullin, a hypotensive peptide, between arterial and venous umbilical cord blood of uncomplicated gestations with vaginal delivery., Study Design: Arterial and venous umbilical cord blood was obtained immediately after vaginal delivery of 44 term infants with uncomplicated antepartum and intrapartum courses. Radioimmunoassay was performed to assess adrenomedullin concentrations in the plasma. The paired t test was used to compare arterial and venous concentrations. Significance was set at P < .05., Results: Mean +/- SE adrenomedullin concentrations were 178.7 +/- 4.7 pg/mL and 190.6 +/- 6.3 pg/mL for arterial and venous cord plasma, respectively. The difference between the 2 concentrations was not significant (11.8 pg/mL, P = .09)., Conclusion: Arterial and venous umbilical plasma concentrations of adrenomedullin do not differ significantly in uncomplicated gestations terminating with uncomplicated vaginal deliveries. This suggests that in the normal state there is neither net production nor net clearance of adrenomedullin in the placenta.

Objectives: Our purpose was to determine the effects of acidosis and acidosis-hypoxia on fetoplacental perfusion pressure and its response to angiotensin II., Study Design: Perfused cotyledons from 14 placentas were studied with either an acidotic fetal circuit perfusate (n = 7) or an acidotic-hypoxic fetal circuit perfusate (n = 7). Each cotyledon's fetal vasculature was initially perfused under standard conditions and bolus injected with 1 x 10(-10) moles of angiotensin II. Fetoplacental perfusate was then replaced with either an acidotic medium (pH 6.90 to 7.00 and Po2 516 to 613 mm Hg) or an acidotic-hypoxic medium (pH 6.90 to 7.00 and Po2 20 to 25 mm Hg) followed by an angiotensin II injection. The vasculature was subsequently recovered with standard perfusate and again injected with angiotensin II. Perfusion pressures within each group were compared by one-way analysis of variance, and results were expressed as mean pressure +/- SEM., Results: Resting fetoplacental perfusion pressure did not change when the fetal circuit perfusate was made acidotic (28 +/- 1 mm Hg vs 25 +/- 2 mm Hg) or acidotic-hypoxic (26 +/- 2 mm Hg vs 25 +/- 2 mm Hg). The maximal fetoplacental perfusion pressure achieved in response to angiotensin II did not differ with an acidotic perfusate (41 +/- 2 mm Hg vs 38 +/- 1 mm Hg) or with an acidotic-hypoxic perfusate (39 +/- 2 mm Hg vs 36 +/- 2 mm Hg)., Conclusions: In the perfused placental cotyledon fetoplacental perfusion pressure and pressor response to angiotensin II are not affected by fetal circuit acidosis or acidosis-hypoxia. This suggests that neither fetal acidosis nor fetal acidosis combined with hypoxia has a direct effect on fetoplacental vascular tone.

Objective: Our purpose was to investigate perfusion pressure changes ex vivo induced by angiotensin II on fetoplacental vasculature pretreated with low-dose acetylsalicylic acid., Study Design: Two cotyledons from each of 12 placentas were perfused. The intervillous space of one cotyledon was infused with acetylsalicylic acid (5 x 10(-5) mol/L) similar to the serum concentration of women receiving daily low-dose aspirin therapy (60 to 81 mg). The control cotyledon was infused with an equivalent amount of normal saline solution. Two doses of angiotensin II, 1 x 10(-11.5) and 1 x 10(-10) moles, were injected as boluses into the chorionic arteries of each cotyledon. A 3 x 10(-7) mole dose of angiotensin II was also injected into the intervillous space. Statistical analysis was performed with analysis of variance, and results are expressed as mean pressure change in millimeters of mercury +/- SEM., Results: Perfusion pressure response did not vary between cotyledons pretreated with acetylsalicylic acid and control cotyledons when 3 x 10(-7) moles of angiotensin II was injected into the intervillous space (8.0 +/- 1.9 mm Hg vs 9.8 +/- 1.6 mm Hg, p = 0.59). There were no differences between cotyledons in pressure response to 1 x 10(-11.5) moles of angiotensin II injected into the fetal circuit (5.9 +/- 0.8 mm Hg vs 6.7 +/- 0.9 mm Hg, p = 0.51). However, in the cotyledons pretreated with acetylsalicylic acid there was a decrease in the pressor response to 1 x 10(-10) moles of angiotensin II (14.1 +/- 1.4 mm Hg vs 21.5 +/- 3.3 mm Hg, p = 0.05)., Conclusions: Low-dose aspirin infused into the intervillous space decreases vasoconstriction elicited by angiotensin II in the fetoplacental compartment. This suggests that maternal low-dose aspirin therapy has effects in the fetoplacental circulation in addition to its effects in the maternal circulation.

Oxalyl thiolesters, a group of putative intracellular regulators, have been shown to be in vitro inhibitors of some cytosolic enzymes which are stimulated by insulin. In this study, the effects of insulin and oxalyl thiolesters on pyruvate dehydrogenase, beta-oxidation, and acyl-CoA hydrolase activities in mitochondria from rat epididymal adipocytes are compared. Using glutathione, CoASH, cysteine, and cysteamine as thiol sources, oxalyl thioesters were synthesized, purified, and quantitated. Mitochondria were isolated from rat epididymal adipocytes, some of which were incubated with or without insulin. Mitochondrial activities were determined by radioisotopic assay subsequent to control, insulin, or oxalyl thiolester incubation. Under the conditions used in this study, pyruvate dehydrogenase activity was increased 28% subsequent to 10-min incubation of adipocytes with 400 microU/ml insulin; in contrast, preincubation of adipocyte mitochondria with S-oxalylglutathione resulted in a dose-dependent 11-19% inhibition of pyruvate dehydrogenase. S-oxalylglutathione also attenuated the spermine-induced activation of pyruvate dehydrogenase. Insulin treatment resulted in a small but significant increase in beta-oxidation of palmitic acid while 100 microM S-oxalylglutathione mediated a 40% decrease in palmitate oxidation. Palmitoyl-CoA hydrolase activity was decreased 14% by insulin treatment; however, S-oxalylglutathione caused a 14-50% increase in hydrolase activity. The other oxalyl thiolesters were not as effective or as consistent as S-oxalylglutathione in modulation of the mitochondrial activities; free thiols and oxalic acid did not modulate the activities. In summary, pyruvate dehydrogenase, palmitate beta-oxidation, and palmitoyl-CoA hydrolase activities in adipocyte mitochondria were modulated in approximately equal but opposite directions by insulin and S-oxalylglutathione. These findings support the suggestion that oxalyl thiolesters may function as an intracellular signal recruited to return insulin to normal levels.

To screen fibroblasts for defects in lactate/pyruvate oxidation, cells were grown to confluence in 25-cm2 flasks, rinsed, and incubated in glucose-free media containing 25 microM L-lactate and 0.1 microCi [D,L-1-14C]lactate. Lactate oxidation was measured as the amount of lactate oxidized in nmol of 14CO2 generated/mg protein/min. Fibroblasts from patients with mitochondrial or peroxisomal disorders had decreased lactate oxidation compared to the control (CON): CON, 1.9 +/- 0.13 nmol/mg/min; neonatal adrenoleukodystrophy (NALD), 0.45 +/- 0.01 (P < 0.001); rhizomelic chondrodysplasia punctata (RCDP), 0.13 +/- 0.002 (P < 0.001); mitochondrial defect of unknown etiology (MIT), 0.77 +/- 0.003 (P < 0.001); pyruvate dehydrogenase (PDH) deficiency, 0.98 +/- 0.02 (P < 0.001). This method is useful for screening fibroblasts for defects in lactate oxidation in patients with mitochondrial or peroxisomal disorders. Confirmation of the site of the defect may then be investigated with specific assays, e.g., PDH, in cellular homogenates: CON, 0.93 +/- 0.02 nmol/mg/min; NALD, 0.55 +/- 0.02; RCDP, 0.44 +/- 0.02; MIT, 0.53 +/- 0.03; PDH deficiency, 0.19 +/- 0.02.