How common are complications following polypropylene mesh, biological xenograft and native tissue surgery for pelvic organ prolapse? A secondary analysis from the PROSPECT trial.

OBJECTIVE: To report complication rates following prolapse surgery using polypropylene mesh inlay, polypropylene mesh kit, biological collagen xenografts and native tissue repairs. DESIGN: Secondary analysis of the PROSPECT randomised controlled trial and cohort study. SETTING: Thirty-five UK hospitals. POPULATION: A total of 2632 women undergoing anterior and/or posterior vaginal prolapse repair. METHODS: Event rates were calculated for all complications. Analysis was by treatment received. MAIN OUTCOME MEASURES: IUGA/ICS classification of complications and validated patient reported outcome measures. RESULTS: At baseline, 8.4% of women had 'generic' pain/discomfort; at 2 years following surgery, there was an improvement in all four groups; however, 3.0% of women developed de novo extreme generic pain. At 24 months de novo vaginal tightness occurred in 1.6% of native tissue, 1.2% of biological xenograft, 0.3% of mesh inlay and 3.6% of mesh kit. Severe dyspareunia occurred in 4.8% of native tissue, 4.2% of biological xenograft, 3.4% of mesh inlay repairs and 13.0% of mesh kits. De novo severe dyspareunia occurred in 3.5% of native tissue, 3.5% of biological xenograft, 1.4% of mesh inlays and 4.8% of mesh kits. Complications requiring re-admission to hospital, unrelated to mesh, affected 1 in 24 women; the most common reasons for re-admission were vaginal adhesions, urinary retention, infection and constipation. CONCLUSIONS: This is the first study to address the complications of vaginal mesh used for prolapse surgery alongside data from both native tissue and biological xenograft. It demonstrates the complexity of assessing pain and that all types of prolapse surgery have low surgical morbidity and a low rate of severe complications. TWEETABLE ABSTRACT: A prospective study of 2362 women undergoing vaginal mesh, xenograft or native tissue repair found low surgical morbidity and low rates of severe complications.

Mesh inlay, mesh kit or native tissue repair for women having repeat anterior or posterior prolapse surgery: randomised controlled trial (PROSPECT).

OBJECTIVE: To compare standard (native tissue) repair with synthetic mesh inlays or mesh kits. DESIGN: Randomised controlled trial. SETTING: Thirty-three UK hospitals. POPULATION: Women having surgery for recurrent prolapse. METHODS: Women recruited using remote randomisation. MAIN OUTCOME MEASURES: Prolapse symptoms, condition-specific quality-of-life and serious adverse effects. RESULTS: A Mean Pelvic Organ Prolapse Symptom Score at 1 year was similar for each comparison (standard 6.6 versus mesh inlay 6.1, mean difference [MD] -0.41, 95% CI -2.92 to 2.11: standard 6.6 versus mesh kit 5.9, MD -1.21 , 95% CI -4.13 to 1.72) but the confidence intervals did not exclude a minimally important clinical difference. There was no evidence of difference in any other outcome measure at 1 or 2 years. Serious adverse events, excluding mesh exposure, were similar at 1 year (standard 7/55 [13%] versus mesh inlay 5/52 [10%], risk ratio [RR] 1.05 [0.66-1.68]: standard 3/25 [12%] versus mesh kit 3/46 [7%], RR 0.49 [0.11-2.16]). Cumulative mesh exposure rates over 2 years were 7/52 (13%) in the mesh inlay arm, of whom four women required surgical revision; and 4/46 in the mesh kit arm (9%), of whom two required surgical revision. CONCLUSIONS: We did not find evidence of a difference in terms of prolapse symptoms from the use of mesh inlays or mesh kits in women undergoing repeat prolapse surgery. Although the sample size was too small to be conclusive, the results provide a substantive contribution to future meta-analysis. TWEETABLE ABSTRACT: There is not enough evidence to support use of synthetic mesh inlay or mesh kits for repeat prolapse surgery.

Why don't women participate? A qualitative study on non-participation in a surgical randomised controlled trial.

INTRODUCTION AND HYPOTHESIS: The objective of the study was to identify reasons why women declined participation in a pilot randomised controlled trial (RCT) comparing tension-free vaginal tape (TVT) under general anaesthetic (GA) with single incision sling (SIS) under local anaesthetic (LA). These data would inform the design of a larger trial to improve patient recruitment. METHODS: This was a qualitative interview study on women eligible to have a TVT for stress urinary incontinence in a tertiary referral hospital in the UK. Women were counselled in a standardised manner. They were informed that the short-term success rates were similar for both operations. Women who declined to take part in the RCT were interviewed using a topic guide. Themes and sub-themes on non-participation were identified by two independent observers using a constant comparison method. RESULTS: Twenty-three non-participants of the RCT were interviewed. Common themes for non-participation were a preference for TVT and request for GA. Sub-themes showed that the TVT was preferred due to its perceived better efficacy as well as a minimal benefit from a SIS and also an unwillingness to take unknown risks. GA was favoured due to fear of local awareness, past negative experiences and embarrassment. Additional tests and follow-up visits were not cited as a reason for non-participation. CONCLUSIONS: The study found that non-participants are not research averse in general but they had strong preferences about specific aspects of treatment. Risk propensity and personality may also influence this behaviour. The study also demonstrates how a qualitative pilot study may improve trial design.

Periurethral abscess following polyacrylamide hydrogel (Bulkamid) for stress urinary incontinence.

Bulkamid is a periurethral bulking agent used to treat stress urinary incontinence (SUI). Manufacturers describe it as nontoxic, nonbiodegradable and biocompatible. Periurethral abscesses are one of the known complications of bulking agents. We present the first reported case of periurethral abscess following Bulkamid injection. The woman had previously had a transobturator tape (TOT) and total vaginal mesh repair. At 6 weeks after injection of the bulking agent, she reported 100 % cure of her SUI. Transperineal ultrasound was used to diagnose and monitor an abscess that developed anterior and lateral to the urethra and separate from the TOT. Magnetic resonance imaging was helpful in delineating the extent of the abscess into the retropubic space but was not able to identify the urethra or the TOT. Surgical drainage of the abscess was performed vaginally, resulting in successful resolution of pain but recurrence of incontinence.

Occurrence and metabolic activity of organisms under the ross ice shelf, antarctica, at station j9.

Seawater samples below the Ross Ice Shelf were collected through an access hole at J9, approximately 400 kilometers from the Ross Sea, Antarctica. The 237-meter water column had sparse populations of bacteria (8.7 x 10(6) to 1.2 x 10(7) per liter), microplankters (10(2) to 10(3) per cubic meter), and zooplankters (10 to 20 per cubic meter) at the depths studied. Microbial biomass estimates from cellular adenosine 5'-triphosphate measurements were very low (10 to 150 nanograms of carbon per liter), comparable with values for the abyssal ocean. Microbial populations assimilated tritiated D-glucose, thymidine, uridine, and adenosine triphosphate at extremely low rates, comparable with deep-sea heterotrophic populations. Sediment samples had 10(7) to 10(8) bacteria per gram (dry weight), which were metabolically active as shown by respiration of uniformly labeled D-[(14)C]glucose. From this study it cannot be determined whether these organisms in the water column and sediments constitute a functioning food web.

A prospective study of laparoscopic sacrocolpopexy for the management of pelvic organ prolapse.

OBJECTIVE: Assessment of the 2-year outcome of laparoscopic sacrocolpopexy. DESIGN: A prospective observational study of women undergoing laparoscopic sacrocolpopexy for prolapse. SETTING: A tertiary referral unit in the North West of England. POPULATION: A total of 22 women taking part in a prospective longitudinal study of prolapse who had a laparoscopic sacrocolpopexy between September 2002 and January 2005. METHODS: Women attended a research clinic where they completed validated quality-of-life questionnaires and were examined. Women were assessed preoperatively and postoperatively at 6 months, 1 year and 2 years. MAIN OUTCOME MEASURES: Pelvic organ support assessed by Pelvic Organ Prolapse Quantification score. Assessment of the degree and impact of vaginal, urinary and bowel symptoms using validated quality-of-life questionnaires. RESULTS: At a mean follow up of 26.5 months, all 22 women had stage 0 vault support with 21 cured of prolapse symptoms. Stress urinary incontinence resolved in half of women without concomitant continence surgery. Bowel symptoms were uncommon, but of those reporting postoperative bowel symptoms, approximately one-third had no symptoms prior to surgery. No new onset dyspareunia was reported in those women sexually active at 2 years. CONCLUSIONS: Laparoscopic sacrocolpopexy is a safe and effective treatment for vault prolapse, providing excellent vault support in the medium term. The outcome for anterior and posterior support is less predictable, and anatomical outcome correlated poorly with functional outcome.

The ER-rosette inhibition assay as a test for immune complexes.

Soluble transferrin-anti-transferrin (TAT) complexes were shown by EA-rosette inhibition assay to block human lymphocyte receptors for the Fc of reacted IgG (Fc gamma) in vitro. These complexes, which provide a convenient and controlled source of Fc gamma receptor blocking material, were found to inhibit EA-rosette formation over a wide range of antigen: antibody ratios. Complexes were detected at both 37 degrees C and 4 degrees C although the range and sensitivity of the assay was markedly increased at 4 degrees C. The inhibitory capacity of TAT complexes was lost on pre-incubation with normal human serum suggesting that only non-complement fixing complexes are detected by EA-rosette inhibition. "False positive" inhibition by antilymphocyte antibodies occurs at 37 degrees C but not at 4 degrees C. Partial automation of the assay was achieved by calibrating a Coulter counter for rosette counting, thus obviating the requirement for tedious and subjective microscopic determinations.

Parenteral exposure to detomidine and butorphanol.

We report a case of intramuscular injection of detomidine and butorphanol in a 36 year-old-man who recovered without sequelae. Detomidine is an alpha 2 adrenergic agonist, similar to clonidine. Detomidine (Domosedan) and butorphanol (Stadol) are commonly used as preanesthetics and to produce chemical restraint, sedation and analgesia in animals, especially horses, but there are no published reports of human toxicity.

A novel mitochondrial point mutation in a maternal pedigree with sensorineural deafness.

We have detected a novel mitochondrial mutation in a maternal pedigree, at least 13 of whose members have sensorineural hearing loss of varying severity, but who exhibit no other pathological features. The mutation, at np 7445, converts the 3' terminal T residue of tRNA-ser(UCN) to a C, and also brings about a silent alteration to the COI stop codon. The mutation destroys an XbaI site, within which a second mutation, at np 7444, has previously been reported in association with Leber's hereditary optic neuropathy. Predominantly mutant mtDNA was found in all 13 family members surveyed, whether or not they are overtly affected by deafness, and some individuals appeared homoplasmic, within the limits of detection. The novel mutation was not found in over 600 normal controls, nor in any of 27 other maternally unrelated individuals with deafness Other mutations found in mitochondrial disorders were also absent from this pedigree.

Immune-complex inhibition of lymphocyte Fc gamma-receptors in primary biliary cirrhosis: a possible immunomodulatory mechanism.

20 patients with primary biliary cirrhosis (PBC) had circulating IgG-containing immune complexes. These complexes bind to lymphocyte Fc gamma-receptors in vitro; there was also evidence for in-vivo binding. Such in-vivo binding to T and K lymphocytes may exert an immunomodulatory effect on these cells, and may also explain some of the serological and cellular abnormalities in PBC.

Lymphocyte emperipolesis revisited. II. Further characterization of the lymphocyte subpopulation involved.

We have previously shown that lymphocyte emperipolesis, the phenomenon whereby lymphocytes wander freely within the cytoplasm of larger host cells, is almost totally dependent on host cell pre-sensitization with IgG type antibody. In addition, the particular lymphocyte subpopulation involved was partially characterized as an Fc receptor bearing, non-T cell. In this study we have attempted to further define the emperipoletic lymphocyte subpopulation using cell fractionation procedures and correlation analysis. Significant correlation was found between emperipolesis and both Fc receptor bearing, surface immunoglobulin negative (Fc + SIg-) cells and antibody dependent lymphocyte mediated cytotoxicity; observations which suggest that the so-called K cells are the emperipoletic effector cells. The significance of these findings in relation to antibody dependent cytolysis is discussed.

Bilateral sensorineural hearing loss in members of a maternal lineage with mitochondrial point mutation.

Pure-tone audiometry was carried out on members of a recently described maternal lineage with sensorineural deafness, harbouring a novel mitochondrial mutation in the gene for tRNA-ser(UCN). This revealed a characteristic pattern of symmetrical bilateral sensorineural hearing losses in each affected individual, predominantly affecting the high-frequencies, but with considerable variability between individuals. No clear correlation was observed between age and severity, but most subjects reported progressive worsening of their condition. Some members of the lineage were found to be heteroplasmic for the tRNA-ser(UCN) mutation. However, the severity of hearing loss was poorly correlated with the representation of the mutant mtDNA, indicating that other, as yet unidentified factors must be involved in the aetiology of this disorder.

Molecular phenotype of a human lymphoblastoid cell-line homoplasmic for the np 7445 deafness-associated mitochondrial mutation.

We have studied mitochondrial gene expression and metabolic function in a human lymphoblastoid cell-line homoplasmic for the np 7445, deafness-associated mitochondrial DNA mutation. The mutation maps to the 3' termini of the oppositely oriented genes encoding cytochrome oxidase subunit I (COI) and tRNA-ser(UCN). In comparison with control lymphoblastoid cells, we detected a marked depletion (> 60%) of tRNA-ser(UCN). There was, however, no significant impairment of respiratory function, no alteration to the structure or abundance of COI mRNA or its precursors, and no detectable abnormality of mitochondrial protein synthesis. We also found considerable tissue-variation in the abundance of tRNA-ser(UCN). We propose that the tissue-specific phenotype associated with this mutation results from an inherent deficiency in the processing of the mutant pre-tRNA, that becomes limiting for protein synthesis only in a restricted set of cells of the auditory system in which the tRNA is, for other reasons, already at a critically low level.

Modulation of human peripheral blood lymphocyte Fc gamma receptors by immune complexes: recovery of Fc gamma receptors in the presence of normal human serum.

When normal human peripheral blood lymphocytes (PBL) were incubated at 37 degrees with soluble transferrin anti-transferrin (TAT) complexes a significant reduction in the proportion of PBL bearing receptors for the reacted Fc portion of IgG(Fc gamma R) was found. Following incubation of such complex-treated PBL in normal human serum the proportion of Fc gamma R + PBL, as assessed by rosette formation with chicken erythrocytes (E) presensitized with rabbit antibody (A) was found to be significantly increased. Such serum-mediated recovery of Fc gamma R was not affected by pretreating PBL with cycloheximide. Recovery was found to be species restricted, Ca++ dependent and confined to a serum fraction containing molecules of relatively low molecular weight (less than 90,000 Mr). Following absorption with EA the restorative capacity of human serum was lost. These findings suggest that following modulation of human PBL-Fc gamma R by immune complexes, receptors may be restored to the cell surface from a serum pool of 'fluid-phase' Fc gamma R. The origin and biological significance of serum Fc gamma R is not known but it is conceivable that they play an important role in immunoregulation.

In vivo modulation of human lymphocyte Fc gamma-receptors in response to oral antigen (cows' milk) challenge.

Following consumption of 1.2 litres of cows' milk by normal human adults there was a rapid fall in the proportion of peripheral blood lymphocytes bearing receptors for the reacted Fc of IgG (Fc gamma-receptors). This phenomenon was transient and apparently confined to the lymphocyte Fc gamma-receptor+ve subpopulation. Similar observations were made in rats but only in those animals pre-exposed to cows' milk suggesting that an immunological mechanism is involved. In man it was found that Fc gamma-receptors could only be re-expressed following incubation of post-milk lymphocytes in normal human serum. It is proposed that rapid in vivo modulation of lymphocyte Fc gamma-receptors occurs following oral antigen (cows' milk) challenge probably mediated by soluble food antigen-antibody complexes. The subsequent recovery of these receptors in vivo and in vitro may be due to the binding of 'fluid-phase' Fc gamma-receptors found in normal human serum.

Sulfur mustard-induced skin burns in weanling swine evaluated clinically and histopathologically.

Histopathological indicators and clinical observations were used to evaluate wound severity, depth and degree of healing on days 2 and 8 for full-skin-thickness sulfur-mustard (HD)-induced burns in weanling swine. Six female weanling swine were exposed for 2 h to 400 microl of HD at each of six dose sites on the hairless abdominal skin. Biopsy samples (8 mm) were taken from the periphery and from the center of the wound on day 2, and the wound was excised on day 8. Histopathological indicators evaluated were epidermal necrosis, follicular necrosis, dermal necrosis, vascular necrosis, depth of injury, ulceration (loss of epidermis), granulation tissue response, neovascularization, re-epithelialization (hyperplasia) and completeness of healing. Wounds were more severe from anterior to posterior. Histopathological assessment of epidermal ulceration and necrosis of epidermis, dermis, basal epithelium, adnexal structures and subcutaneous tissue were useful indicators of wound development on day 2. Granulation tissue response (observed as early as day 8) and re-epithelialization were good indicators of wound healing. Clinical evaluations were performed on day 2 prior to and after debriding, and on study day 8. Clinical observations on study day 2 were for wound size and for exudation, erythema, edema, necrosis and eschar. Clinical observations on study day 8 were for the previous parameters and for re-epithelialization, granulation and infection. Wound size and severity increased from anterior to posterior position. Size, exudation and edema were useful indicators of wound development. These histological and clinical observation parameters will be used in future experiments to compare various treatments for HD-induced burns.

Cutaneous histopathologic features in weanling pigs after exposure to three different doses of liquid sulfur mustard.

Sulfur mustard (2,2' dichlorodiethyl sulfide, HD) is a chemical warfare agent that is easily produced, and may be used against civilian populations as well as against military troops. However, good therapeutic and prophylactic measures await a better understanding of the pathophysiology of lesions produced by this agent. Because the skin remains is one of the principal routes for HD exposure and damage, the study of HD-induced skin lesions is of major interest. Blister formation is a characteristic of HD-induced skin lesions in humans. Attempts have been made to find an animal model that produces cutaneous microblisters after exposure to the naturally occurring liquid as well as vaporized HD. Weanling pigs were exposed to three different doses of liquid HD. Histopathologic findings showed microblister formation as well as variable apoptosis and/or necrosis of epidermal keratinocytes and vascular endothelium. Pig skin is morphologically similar to human skin. In the pig, the epidermal lipids, the density of hair follicles, the presence of sweat glands, the proliferation kinetics, and the antigenicity are all closer to human skin than are rodent models. All these features may be important in lesions induced by HD, and may mean that the pig is a superior model for studying the pathophysiology of HD-induced cutaneous lesions.

Serum-mediated inhibition of human lymphocyte fc gamma-receptors in extrinsic and intrinsic bronchial asthma.

Sera from 48 patients with extrinsic asthma and 37 with intrinsic asthma were screened for immune complexes using the EA-rosette inhibition assay. Significant levels of EA-rosette inhibition were found in both groups when compared with normal sera. The serum inhibitory factor(s) is, however, more likely to be an anti-lymphocyte antibody of the IgM class than an immune complex as originally expected.

Reduction in peripheral blood K cells and activated T cells in primary biliary cirrhosis.

Lymphocyte subpopulations were measured in the peripheral blood of 13 patients with primary biliary cirrhosis (PBC), 13 with chronic active hepatitis (CAH), and 16 age- and sex-matched normal subjects. A significant, relative and absolute, reduction in activated T cells and K cells, compared with that in normal subjects, was found in PBC but not in CAH. The reduction in K cells observed in PBC was found to be accompanied by a parallel decrease in lymphocyte-mediated antibody-dependent cytotoxicity.