Accidental bowel leakage in the mature women's health study: prevalence and predictors.

BACKGROUND: The 2007 National Institutes of Health incontinence consensus panel emphasised the need for classification and identification of persons at risk for faecal incontinence (FI). OBJECTIVES: To explore the prevalence of FI; to characterise severity and 'bother'; and to identify factors associated with FI in a large sample of community-dwelling women. DESIGN, SETTING, AND PARTICIPANTS: A cohort of US women ≥ 45 years old was surveyed via an internet-based questionnaire between September 2009 and April 2010. MAIN OUTCOME MEASURE: Accidental leakage of liquid or solid stool at least once in the last 12 months. KEY RESULTS: Eighty-five per cent of those surveyed (5817/6873) participated and were predominantly white, well educated and insured. The prevalence of FI at least once in the past year was 18.8% (1096/5817; 95% CI: 17.8-19.9%) and 97% of these women were bothered by this frequency of leakage. Among 938 respondents with FI, 71.1% (667) preferred the term 'accidental bowel leakage' (ABL) over faecal or bowel incontinence. Bowel disorders, urinary incontinence, stroke, age 55-64, diabetes mellitus and prior vaginal delivery were associated with an increased odds of FI, whereas being married, Black or American Indian/Alaska Native race/ethnicity, and income ≥ $40,000 per year were associated with a decreased odds of FI. CONCLUSIONS: Nearly one-fifth of mature US women suffer from bothersome leakage of stool at least yearly and the overwhelming majority prefer the term 'Accidental Bowel Leakage.' Those with bowel disorders and urinary incontinence are most likely to experience ABL. Incorporating questions regarding ABL or bowel and bladder disorders into routine screening may aid in identifying silent sufferers of ABL.

Quality of life impact in women with accidental bowel leakage.

BACKGROUND: Accidental bowel leakage (ABL) is associated with negative impact on quality of life (QoL) and many women do not seek care. OBJECTIVES: To assess current perspectives and QoL among women with ABL; to identify factors associated with severe impact on condition-specific QoL; and to describe care-seeking for ABL. DESIGN, SETTING AND PARTICIPANTS: Sub-analysis of 1096 women with ABL identified through an internet-based, self-administered survey of 5817 US women ≥ 45 years old. MAIN OUTCOME MEASURE: Severe impact on QoL was defined as response of 'affects very much' or 'greatly' to any of seven domains within Pelvic Floor Impact Questionnaire. RESULTS: QoL data were available for 85.6% (938/1096) of women with ABL. Domains relating to frustration, emotional health and participation in social activities demonstrated the greatest negative impact, with 39.2% (95% CI 36.1-42.4%) having overall severe impact. More frequent ABL, faecal urgency, nocturnal bowel movements, FI without warning, stress FI, weekly urinary incontinence and underlying bowel disorder were associated with severe impact on QoL. Of the 28.6% (268/938) of women who spoke to a physician about their ABL, the majority did so with a general practitioner or family physician (56.0%, 150/268). Only 19.0% (51/268) consulted an internist or gastroenterologist [27.2% (73/268)]. CONCLUSIONS: Nearly 40% of adult women with ABL have severe negative impact on QoL, but less than one-third seek care. More than half of those who seek care do so with their primary care provider. Improved awareness of the prevalence and impact of FI by these providers may decrease barriers and improve QoL.

Upregulation of ß-cell genes and improved function in rodent islets following chronic glucokinase activation.

Glucokinase (GK) plays a critical role in controlling blood glucose; GK activators have been shown to stimulate insulin secretion acutely both in vitro and in vivo. Sustained stimulation of insulin secretion could potentially lead to ß-cell exhaustion; this study examines the effect of chronic GK activation on ß-cells. Gene expression and insulin secretion were measured in rodent islets treated in vitro with GKA71 for 72 h. Key ß-cell gene expression was measured in rat, mouse and global GK heterozygous knockout mouse islets (gk(del/wt)). Insulin secretion, after chronic exposure to GKA71, was measured in perifused rat islets. GKA71 acutely increased insulin secretion in rat islets in a glucose-dependent manner. Chronic culture of mouse islets with GKA71 in 5 mmol/l glucose significantly increased the expression of insulin, IAPP, GLUT2, PDX1 and PC1 and decreased the expression of C/EBPß compared with 5 mmol/l glucose alone. Similar increases were shown for insulin, GLUT2, IAPP and PC1 in chronically treated rat islets. Insulin mRNA was also increased in GKA71-treated gk(del/wt) islets. No changes in GK mRNA were observed. Glucose-stimulated insulin secretion was improved in perifused rat islets following chronic treatment with GKA71. This was associated with a greater insulin content and GK protein level. Chronic treatment of rodent islets with GKA71 showed an upregulation of key ß-cell genes including insulin and an increase in insulin content and GK protein compared with glucose alone.

Human immunodeficiency virus in plasma and cervicovaginal secretions in Filipino women.

This study examined 30 HIV-infected women in Manila to assess the relationship between cervicovaginal and plasma HIV-1 viral load. An interview and gynaecologic examination was conducted and cervicovaginal lavage (CVL) and venous blood specimens were collected. HIV-1 RNA was detected in plasma samples of 24 patients (80%) and in CVL samples of 18 women (60%); 16 patients (53%) had detectable levels in both. CVL HIV-1 RNA was detectable in 75% of women (6/8) with plasma viral loads between 10,000 and 100,000 copies/mL and in 77% of women (10/13) with plasma viral loads higher than 100,000 copies/mL (P =0.0086). Among women with CD4 cell counts of less than 200, 200-500, and greater than 500/mm(3), CVL HIV-1 RNA was detected in 73%, 69%, and 17% of women, respectively (P =0.1428). HIV-1 RNA shedding in the genital tract was significantly associated with plasma viral load.

Increase in brain stem cytokine mRNA levels as an early response to chemical-induced myelin edema.

This study examined the early response of pro-inflammatory and regulatory cytokines in the mouse brain following triethyltin (TET)-induced myelin injury characterized by edematous vacuolation. Following an acute intraperitoneal injection of triethyltin (TET) sulfate (3 mg/kg) to 17-day old CD1 mice, significant increases in brain stem TNF-alpha and IL-1alpha mRNA levels occurred at 6 and 24 h, respectively with elevations in TGF-beta1 and MIP-1alpha at 1 h. In the cortex, responses were limited to elevations at 6 h in TNF-alpha, TGF-beta1 and MIP-1alpha. These data suggest that a chemokine/cytokine response can occur with minimal alterations to the integrity of the myelin sheath and may contribute to the initial signaling mechanisms associated with demyelinating disorders.

Protection against tetanus toxin in mice nasally immunized with recombinant Lactococcus lactis expressing tetanus toxin fragment C.

Mice inoculated intranasally (i.n.) with a recombinant strain of live Lactococcus lactis expressing tetanus toxin fragment C (TTFC), produced both serum and secretory antibodies to TTFC. Killed bacteria which had accumulated TTFC intracellularly in vitro also elicited protective serum antibody responses. There was no requirement for either colonization or invasion of the mucosa. In addition secretory antibody responses in the lung and nasal tissues were elicited after i.n. inoculation in the presence of an adjuvant.

Induction of tumor necrosis factor alpha in cultured glial cells by trimethyltin.

Within the central nervous system, cytokines are thought to play an active role in pathophysiological changes seen in various neurodegenerative diseases and trauma. Previous studies in our laboratory demonstrated that systemic administration of the neurotoxicant trimethyltin (TMT) produced a rapid and sustained elevation of CNS TNF alpha mRNA levels. In order to examine the effects of TMT on glial cultures in the absence of a neuronal component, primary glial cultures were exposed to TMT. Cultured glial cells undergo distinct morphological changes within 6 h of exposure to 10 microM TMT. This is characterized by an initial retraction of astrocytic processes revealing long, thin GFAP-dense processes and enlarged cell bodies, progressing to distinct retraction of plasmalemmna processes by 24 h. Prior to morphological changes, mRNA levels for the astrocyte-specific protein, glial fibrillary acidic protein (GFAP), increased within 3 h, as determined by Northern blot hybridization. Approximately a four-fold increase in TNF alpha mRNA levels was observed after 6 h as determined by competitive RT-PCR. This stimulation resulted in a 10-fold increase in the biologically active form of TNF alpha protein. These results suggest that a direct stimulation of glial cells may produce an early and critical response of the nervous system in chemical-induced neurotoxicity.

Factors affecting the immunogenicity of tetanus toxin fragment C expressed in Lactococcus lactis.

The relative immunogenicity of tetanus toxin fragment C (TTFC) has been determined in three different strains of inbred mice when expressed in Lactococcus lactis as a membrane-anchored protein (strain UCP1054), as an intracellular protein (strain UCP1050), or as a secreted protein which is partly retained within the cell wall (strain UCP1052). Protection against toxin challenge (20 x LD50) could be obtained without the induction of anti-lactococcal antibodies. When compared in terms of the dose of expressed tetanus toxin fragment C required to elicit protection against lethal challenge the membrane-anchored form was significantly (10-20 fold) more immunogenic than the alternative forms of the protein.

Lateral hemostatic sutures in cold knife conization of the cervix. What do they accomplish?

OBJECTIVE: The purpose of cold knife conization is to ligate the descending cervical branch of the uterine artery and thus to decrease bleeding. The aim of this study was to investigate the actual frequency of ligation. STUDY DESIGN: Two lateral sutures were placed in the cervix at the 3 and 9 o'clock positions in 97 patients (194 sutures) as part of vaginal hysterectomy. The position of each suture was determined during evaluation of the surgical specimen. RESULTS: Because the specimens from 10 patients contained only single sutures, only 184 sutures were actually evaluated. Upon microscopic examination, 50 of the 184 (27%) appeared to contain no artery. Of the remaining 134 sutures, 95 (71%) enclosed an artery, and 9 (7%) lay within a 10 x field of a branch. Only 30 sutures (22%) missed the artery entirely. Thus, in the 73% of cases where an artery of significant size could be identified, the artery lay within a lateral stitch 71% of the time. CONCLUSION: If the descending cervical branch of the uterine artery supplies most of the blood to the cervix, advance placement of lateral sutures would be expected to reduce blood loss during conization.

Trimethyltin increases interleukin (IL)-1 alpha, IL-6 and tumor necrosis factor alpha mRNA levels in rat hippocampus.

Within the central nervous system (CNS), cytokines are though to have active roles in pathophysiological changes seen in various neurological diseases and trauma. The present study was undertaken to examine the early response of pro-inflammatory cytokines following exposure to a specific neurotoxicant (trimethyltin; TMT). mRNA levels for interleukin (IL)-1 alpha, IL-1 beta, IL-6 and tumor necrosis factor (TNF) alpha were measured in the hippocampus of adult male Long-Evans hooded rats following an acute injection of trimethyltin hydroxide (8 mg TMT/kg body weight). At various times following exposure (6 h to 8 days), hippocampal tissues were excised and relative changes in cytokine mRNA levels were assessed by reverse transcription and polymerase chain reaction. IL-1 alpha, IL-6 and TNF alpha mRNA levels in the hippocampus increased within 6 h and remained elevated for 8 days. Quantitative analysis of mRNA transcripts revealed a two-fold increase in both IL-6 and TNF alpha within 6 h and a continued elevation of TNF alpha to 9-fold by 12 h. Within 96 h, glial fibrillary acidic protein (GFAP) mRNA levels were elevated in the hippocampus. Histological examination showed sparse individual neuronal necrosis at this time in both the pyramidal and granule cell regions with no increase in astrocyte GFAP immunoreactivity. However, an early, 24 h, response of microglial cells was indicated by increased lectin binding. This morphological profile progressed over time to a profound neuronal loss in the CA3-4 granule cell layer and marked astrocyte hypertrophy. The onset of pro-inflammatory cytokine mRNA expression appears to be temporally associated with histological evidence of elevated microglia in the hippocampus. It is proposed that microglia and pro-inflammatory cytokines play a modulatory role in the early stages of TMT-induced neurotoxicity.

The immune response to Lactococcus lactis: implications for its use as a vaccine delivery vehicle.

The development of natural antibodies to Lactococcus lactis in three inbred strains of mice and the effect of inoculating L. lactis into these mice has been investigated. All animals developed detectable levels of natural (systemic and secretory) anti-lactococcal antibodies. Systemic anti-lactococcal antibodies were principally IgG in young mice. An increase in anti-lactococcal IgM occurred in all older animals. Inoculation of L. lactis strains MG1820 or MG1363 by the oral and parenteral routes induced systemic anti-lactococcal antibody responses in a dose-dependent fashion. The relative immunogenicity of individual bacterial proteins varied according to mouse strain and route of inoculation.

Thymocyte injury after in vitro chemical exposure: potential mechanisms for thymic atrophy.

In addition to hepatic injury, thymic atrophy is a common observation in rodent subchronic toxicity studies. We have examined representative chemicals which produce thymic atrophy in rodents for their ability to cause direct thymocyte injury because the mechanism(s) responsible for these effects have not been determined. Although a number of the compounds examined failed to have any observable direct effect on thymocytes, others either inhibited lymphocyte proliferation or initiated cell death. In the latter group, thymocyte death was always preceded by increases in intracellular Ca++ and involved, to varying degrees, necrotic and apoptotic events. Apoptosis, as evidenced by cellular DNA cleavage into multiples of 180-200-base pair oligonucleotides and partial cell protection by cycloheximide treatment, was most evident after treatment with acetaldehyde or dibutyltin dichloride. A number of compounds that produce thymic atrophy also inhibited T lymphocyte proliferation without evidence of cell death. Considering that many of the compounds tested failed to produce any evidence of direct thymocyte injury (i.e., necrosis, apoptosis or inhibition of cell proliferation), indirect mechanisms may also be involved in thymic atrophy and may target prothymocytes in the bone marrow, after normal homing patterns or injure the thymic epithelium. Thus, it appears that a variety of mechanisms may be responsible for chemical-induced thymic atrophy and/or injury.

Rapid selective brain-cooling using head immersion and naso-oral perfusion in dogs.

Utilizing a technique of selective surface head cooling and naso-oral perfusion, rapid profound cooling of the brain to 14-19 degrees C with maintenance of body temperature has been achieved in 24 dogs. Post perfusion, neurological examination of the animals were within normal limits, and neuropathological review of brain specimens demonstrated absence of tissue abnormality.

Juvenile colonic polyposis with villous adenoma and retroperitoneal fibrosis: Report of a case.

A 25-year-old Nigerian black woman was found to have polyps involving the rectum, rectosigmoid, and sigmoid colon on air-contrast barium-enema examination. Resection of a segment of sigmoid colon revealed numerous polyps that were predominantly of the juvenile type, in keeping with the diagnosis of juvenile polyposis of the colon. This case is unusual because of the coexistence of retroperitoneal fibrosis with juvenile polyposis of the colon. In addition, one of the colonic polyps was a villous adenoma. The implications these findings are discussed in relation to polyposis syndromes reported previously.