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Biomedical subjects

C Pope

Publications and source records attributed to C Pope.

At least 37 records · Page 2Linked to original sources

Changes in gastrointestinal morphology associated with obstructive jaundice.

Bacterial translocation has been consistently demonstrated in experimental models of obstructive jaundice. An important factor which promotes this phenomenon is physical injury of the intestinal mucosa. Some previous studies have presented suggestive evidence of this, following bile duct ligation. The aims of this study were to analyse objectively intestinal mucosal morphometric characteristics, to examine for evidence of bacterial translocation, and to assess enterocytes for ultrastructural abnormalities. Adult female Wistar rats were assigned to one of three groups: control (n=8), bile duct ligation (BDL; n=11), or sham operation (n=10). One week later, portal blood, mesenteric lymph nodes, liver, and spleen were harvested and cultured aerobically and anaerobically for evidence of bacterial translocation. Segments of jejunum, ileum, caecum, and large bowel were examined histologically, using light microscopy and morphometrically, using an image analysis system. Electron microscopy was performed on regions of the gastrointestinal tract where significant morphometric alterations had been identified. Significant bacterial translocation was identified following BDL (63. 6% BDL vs. 0% sham vs. 0% control, p<0.01, Fisher's exact test). There was a significant reduction in total mucosal thickness (standard error) [650 microm (23) BDL vs. 731 microm (27) sham vs. 744 microm (95) control] and villous height [451 microm (20) BDL vs. 515 microm (18) sham vs. 559 microm (79) control] in jaundiced animals, compared with sham-operated and control animals (p<0.02, Mann-Whitney U-test). Electron microscopy revealed oedematous change associated with mild inflammation, disruption of desmosomes, and the formation of lateral spaces between enterocytes. In addition, enterocytes showed vacuolation of their cytoplasm and mitochondrial swelling. Increased numbers of bacteria appeared to be attached to the mucosa. These data provide evidence of physical disruption of intestinal mucosa in jaundiced animals, most marked in the distal ileum. Significant bacterial translocation occurs following bile duct ligation and this supports the hypothesis of gut barrier dysfunction with obstructive jaundice.

Animals↗

Carboxylesterase and A-esterase activities during maturation and aging: relationship to the toxicity of chlorpyrifos and parathion in rats.

Chlorpyrifos (CPF) and parathion (PS), two common organophosphorus (OP) pesticides, exhibit higher acute toxicity in younger animals compared to adults. Maturational differences in detoxification via carboxylesterases (CEs) and A-esterases (AEs) have been suggested as contributors to the higher sensitivity of younger animals to OP toxicants. AEs (e.g., chlorpyrifos oxonase and paraoxonase) catalytically inactivate while CEs stoichiometrically eliminate OP anticholinesterases. While earlier studies have reported a relationship between the toxicity of some OP pesticides and the maturational profile of AEs and CEs, little information exists on the relative OP-toxicant sensitivity and detoxification capacities of aged animals. In the present study, we investigated the relationship between toxicity of CPF and PS and the activity of CEs and AEs in liver, plasma, and lung of neonatal (7 day), juvenile (21-day), adult (3-month), and aged (24-month) Sprague Dawley rats. CE sensitivity in vitro to chlopyrifos oxon and paraoxon was also evaluated across age groups. Neonatal and juvenile rats were more sensitive than adults to the acute lethality of both CPF and PS. Aged rats exhibited similar sensitivity to CPF but were markedly more sensitive than adults to PS. Levels of CEs and AEs in neonatal and juvenile rats were significantly lower than in adult tissues. Aged rats showed similar levels of AEs in all tissues and CEs in liver and lung, but plasma CE levels were significantly lower (50%) when compared to the adult rats. There were no significant age-related differences in in vitro sensitivity of CEs to either chlorpyrifos oxon or paraoxon in any tissues. In general, acute sensitivity (MTD) was highly correlated with age-related differences in both esterase activities across all 3 tissues with CPF, but only plasma carboxylesterase activity was highly correlated with sensitivity to parathion. The results suggest that both carboxylesterase and A-esterase activities can be correlated with acute sensitivity to CPF and PS, but that age-related differences in CE activity are probably more important in differential toxicity. Furthermore, plasma carboxylesterase activity may play a more pivotal role in the differential sensitivity to PS.

Age Factors↗

What determines the choice of procedure in stress incontinence surgery? The use of multilevel modeling.

The purpose of this study was to identify the determinants of choice of surgical procedure (anterior colporrhaphy, colposuspension, or needle suspension) to treat stress incontinence in women. We used multilevel modeling of data on 271 patients in 18 hospitals in England in 1993-94. Patient-related factors included sociodemographic details, anatomical diagnosis, symptom severity, symptom impact, previous treatment, parity, comorbidity, and general health status. Surgeon-related factors were specialty, grade, and annual volume of procedures undertaken. Hospital teaching status was considered. Some patient-related factors were associated with choice of procedure: women with a concomitant genital prolapse, with a history of high parity, and with no previous nonsurgical treatment were more likely to undergo an anterior colporrhaphy than a colposuspension or needle suspension (although this finding could be confounded by surgical specialty). In addition, women were more likely to be treated by colposuspension if their surgeon specialized in incontinence surgery (measured by annual volume of cases). Finally, being treated by needle suspension depended on there being a consultant surgeon familiar with the procedure at the hospital attended. While choice of surgical procedure depends partly on the patient's anatomical diagnosis, it is also dependent on the specialty of the surgeon whom she consults and the hospital that she attends. This variability, in turn, could have implications for the patient (as the relative effectiveness of the different procedures is unknown) and for the purchasers of care (as the relative cost-effectiveness of procedures is also unknown).

Adult↗

Impact of surgery for stress incontinence on the social lives of women.

OBJECTIVE: To assess the feasibility of collecting disease-specific and generic data on the impact of surgery on the social lives of women with stress incontinence; to describe the social impact of surgery in a representative group; and to determine the effect of timing on the assessment of outcome. DESIGN: Longitudinal study; questionnaires before and three, six, and twelve months after surgery. SETTING: Eighteen hospitals in North Thames region. PARTICIPANTS: Four hundred and forty-two women undergoing surgery for stress incontinence between January 1993 and June 1994. MAIN OUTCOME MEASURES: Post-operative recovery time, stress incontinence symptom impact index, activities of daily living, and cost of protection. RESULTS: Post-operative recovery was uneventful for most women, but three months after surgery 24% of those in paid employment beforehand were still on sick or unpaid leave. Most women (75%) reported that stress incontinence had less adverse impact on their lives three months after surgery, though 18% reported no change, and 7% felt life was worse. The likelihood of improvement was similar regardless of whether pre-operative urodynamic studies had been conducted. The extent of improvement was dependent on pre-operative severity. Similar findings were obtained six and twelve months after surgery. After an initial slight but nonsignificant deterioration in their ability to carry out activities of daily living, women gained a slight benefit from surgery (proportion with no or only slight limitation rose from 72% to 82%; P=0.0001). The mean cost of protection (pads and towels) fell from 8.59 pound sterling a month before surgery to 2.99 pound sterling a month one year after surgery, by which time 68% of women were not using protection. In contrast, 11% were still spending over 10 pound sterling a month. CONCLUSIONS: It is possible to collect standard data on the impact of surgery on social functioning and, thus, provide women with better information on likely outcomes. The benefits of pre-operative urodynamic investigations need to be assessed. The stability of the outcome measures over the first post-operative year suggest that outcomes need to be assessed only once and at any time from three to twelve months after the operation.

Activities of Daily Living↗

Acute respiratory distress syndrome. Inhaled nitric oxide.

There is enough evidence to support the short-term beneficial effects and safety of administering inhaled NO to ARDS patients. This effect may be potentiated when inhaled NO is administered in conjunction with other therapies. The full spectrum of effects of inhaled NO remains to be elucidated. Long-term benefit in terms of mortality and duration of mechanical ventilation has not been demonstrated; more randomized trials probing these effects are needed.

Administration, Inhalation↗

Impact of surgery for stress incontinence on morbidity: cohort study.

OBJECTIVES: To describe the impact of surgery for stress incontinence on the severity of symptoms, other mental and physical symptoms, and overall health. To describe the incidence of postoperative complications. DESIGN: Prospective cohort study; questionnaires completed by patients before and 3, 6, and 12 months after surgery. Questionnaires completed by surgeons both before and after surgery. SETTING: 18 hospitals in the North Thames region. SUBJECTS: 442 women treated surgically for stress incontinence between January 1993 and June 1994. 367 women returned the 3 month questionnaire; 364 returned the 6 month questionnaire; and 359 returned the 12 month questionnaire. 49 surgeons provided perioperative information on 285 of the 442 women and postoperative information on 278. MAIN OUTCOME MEASURES: Stress incontinence symptom severity index, other urinary symptoms, bowel function, mental health, complications, global measures. RESULTS: Most women (288; 87%) reported an improvement in the severity of their stress incontinence, though only 92 (28%) were cured (continent). These improvements persisted for at least 12 months. The likelihood of improvement was similar regardless of whether urodynamic pressure studies had been conducted before surgery. Following surgery, women were less likely to suffer from urinary frequency, nocturia, postvoid fullness, dysuria, and urgency. While mental health improved for 194 (71%), a quarter of women reported deterioration. Only 37 (10%) were satisfied with postoperative pain control. A third experienced one or more complications while in hospital, most commonly difficulty urinating. This problem affected 1 in 11 women after discharge. A year after surgery two thirds of women reported feeling better (251; 72%), that the outcome met or exceeded their expectations (230; 66%), and that they would recommend the operation to a friend in a similar situation (239; 68%), and that they would recommend the operation to a friend in a similar situation (239; 68%). Surgeons tended to be more optimistic about the effects of surgery; they were satisfied with the outcome in 176 (85%) cases and would again treat 245 (94%) of the women as they had done previously. CONCLUSIONS: Although surgery reduces the severity of stress incontinence it is not as effective as current textbooks suggest. Women considering surgery should be provided with more accurate information on the likelihood of an improvement in symptoms and the occurrence of complications, including postoperative pain. Urgency and urge incontinence should not be considered contraindications to surgery. The need for urodynamic assessment before surgery should be reappraised.

Cohort Studies↗

Improved efficiency for primer extension by using a long, highly-labeled primer generated from immobilized single-stranded DNA templates.

Primer extension is one of the most common methods used to measure the amount and size of RNAs. We demonstrate that the sensitivity and the specificity of this method are improved considerably by using a highly-labeled single-stranded DNA generated from a biotinylated single-stranded DNA template, as a long specific primer in the reverse transcription reaction. This new approach allows the detection of transcripts with a low expression level from microgram quantities of total RNA.

Animals↗

Development of a symptom severity index and a symptom impact index for stress incontinence in women.

Stress incontinence is a common problem among women, yet there is no adequately validated instrument for measuring women's views of its severity (disease-specific health status). The only instrument for measuring the impact or bothersomeness of symptoms (disease-specific quality of life) has poor internal consistency. This paper describes the development and psychometric assessment of two new indexes, a Symptom Severity Index and a Symptom Impact Index. Following several qualitative enquiries, a questionnaire was developed and administered to 442 women undergoing stress incontinence surgery. The face and content validity of the items comprising the indexes was good. The Severity Index (0-20) showed good variability (median 14, interquartile range 6) and adequate internal consistency (alpha 0.76). The Impact Index (0-12) also had good variability (median 5, interquartile range 3.5) and internal consistency (alpha 0.80). Convergent and discriminant validity were demonstrated for both indexes. Test-retest reliability was high. While responsiveness is still to be tested, the two indexes are psychometrically strong and can be used to measure the severity and impact of stress incontinence in women.

Adult↗

Intestinal barrier dysfunction in clinical and experimental obstructive jaundice and its reversal by internal biliary drainage.

Intestinal mucosal barrier function in obstructive jaundice was assessed in an animal model and in patients. The effect of internal biliary drainage in patients was also examined. Bile duct ligation for 1 week in the rat resulted in significant bacterial translocation (in seven of 12 animals following ligation versus none of the shamoperated controls, P < 0.01). Intestinal permeability, measured by the urinary recovery of orally administered polyethylene glycol, was also significantly increased (+66.2 per cent for ligation versus -11.6 per cent for sham, P < 0.01). A prospective study was performed on 33 patients with obstructive jaundice undergoing internal biliary drainage, and results were compared with those in six non-jaundiced patients undergoing laparotomy or endoscopic retrograde cholangiopancreatography and in 11 health volunteers. The lactulose: mannitol ratio was used as an intestinal permeability index. Mean(s.e.m.) intestinal permeability assessed before operation was significantly increased in jaundiced patients compared with control patients (0.050(0.010) versus 0.016(0.003), P < 0.005). The mean(s.e.m.) lactulose: mannitol ratio in the healthy volunteers was 0.020(0.003), which was similar to that in control patients. In the jaundiced group of patients the intestinal permeability index fell to within normal levels after 28 days of internal biliary drainage (0.050 before operation versus 0.021 at 28 days, P < 0.02). These data indicate that intestinal barrier function is impaired in obstructive jaundice and that this impairment is reversed by return of bile to the gastrointestinal tract.

Animals↗

Sociodemographic and symptomatic characteristics of women undergoing stress incontinence surgery in the UK.

OBJECTIVES: To: (i) describe the sociodemographic characteristics of women undergoing surgery for stress incontinence in the UK and the ways in which they differ from women of a similar age in the general population: (ii) the severity and impact of their symptoms and their expectations of surgery and: (iii) their general state of health. PATIENTS AND METHODS: A prospective cohort study was carried out on 442 women undergoing surgery for stress incontinence in 18 hospitals in the North Thames region between January 1993 and June 1994. Sociodemographic factors, stress incontinence severity, symptom impact scores, and general health status were measured. RESULTS: Women undergoing surgery for stress incontinence were similar to their peers in the general population apart from being more likely to have smoked (61.4 against 51.1%), to have subsequently given up (39.5 and 25.3%) and to be of higher parity (> or = 4; 19.7 and 12.0%). Most women (81.6%) reported moderate to very severe stress incontinence. The impact of symptoms was correlated positively with severity (P < 0.001) after accounting for its positive correlation with mental health status (P < 0.005), socioeconomic status (P < 0.05) and its negative correlation with age (P < 0.02). Many women also suffered from other urinary symptoms including urgency (76%) and frequency (42.3%). Apart from their urinary problems, women were in good health (77% reported no or only mild coexistent conditions). However, a very high proportion (34.2%) had previously undergone a hysterectomy. CONCLUSIONS: These results suggest that women undergoing stress incontinence surgery are remarkably similar to their peers, apart from their primary condition. The effect that stress incontinence has on women's lives depends not only on the severity of the problem but also on other factors. The high rate of previous hysterectomy warrants further study.

Adult↗

Bacterial translocation and gut microflora in obstructive jaundice.

Bacterial translocation from the gut is implicated in the pathophysiology of complications associated with obstructive jaundice. Absence of intraluminal bile salts and their antiendotoxic effects may result in overgrowth of bacteria, promoting bacterial translocation. The large bowel is the largest source of gram negative bacteria but the small bowel is more permeable. This study investigated the effect of obstructive jaundice on bacterial translocation and on the indigenous luminal microflora at 3 sites in the gastrointestinal tract. Significant bacterial translocation was demonstrated following 7 d of bile duct ligation compared with control or sham operated groups. A qualitative disturbance of the caecal indigenous microflora was demonstrated in jaundiced rats. There was no 'site-to-site' variation in the indigenous microflora at the 3 intestinal sites studied. We conclude that experimental obstructive jaundice for 1 wk promotes bacterial translocation without significant quantitative disturbance of the intestinal microflora in the small intestinal or caecum.

Animals↗

Qualitative research: Observational methods in health care settings.

Clinicians used to observing individual patients, and epidemiologists trained to observe the course of disease, may be forgiven for misunderstanding the term observational method as used in qualitative research. In contrast to the clinician or epidemiologist, the qualitative researcher systematically watches people and events to find out about behaviours and interactions in natural settings. Observation, in this sense, epitomises the idea of the researcher as the research instrument. It involves "going into the field"--describing and analysing what has been seen. In health care settings this method has been insightful and illuminating, but it is not without pitfalls for the unprepared researcher.

Data Collection↗