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Biomedical subjects

K H Moore

Publications and source records attributed to K H Moore.

At least 19 recordsLinked to original sources

GAP-43 immunoreactivity of subepithelial and detrusor muscle nerve fibres in patients with refractory idiopathic detrusor overactivity.

AIMS: To determine the relative density of nerve fibres immunoreactive to growth associated protein-43 (GAP-43, an indicator of neuronal sprouting) in the subepithelium and detrusor of patients with idiopathic detrusor overactivity (IDO). To investigate the effect, if any, of age and previous recurrent bacterial cystitis on neuronal sprouting in such patients. MATERIALS AND METHODS: A series of 18 women with urodynamically proven IDO (median age 62 years, range 39-85), who were refractory to treatment, underwent cystoscopy and cold cup biopsy. Controls (n=26, median age 65, range 32-79) were females without urgency/urge incontinence, undergoing cystoscopy for other indications. Recurrent proven bacterial cystitis (rUTI) was documented. Frozen sections were stained with specific antibodies to GAP-43 and protein gene product 9.5 (PGP, a general neuronal marker). The area represented by immunoreactive (ir) subepithelial or muscle nerve fibres was measured. RESULTS: The density of GAP-43ir and PGPir nerves did not differ significantly between IDO patients and controls, in either subepithelium or detrusor. The GAP-43ir nerve density (as percent of PGPir) increased significantly with advancing age amongst patients with IDO in the detrusor muscle but not in the subepithelium; density in controls was unaltered. In IDO patients with rUTI, a significant increase in GAP-43 (as percent of PGPir) was observed in the subepithelium. CONCLUSIONS: Although we found no evidence of increased neuronal proliferation in patients with IDO generally, the increase in GAP-43 with age and with previous cystitis history suggests that neuronal sprouting is important in some subsets of patients with IDO.

Adult↗

The repeatability of the 24-hour pad test.

A prospective observational study was conducted in a tertiary urogynaecology unit in women with the primary symptom of urinary incontinence to assess the repeatability of the 24-hour pad test. One hundred and eight women undertook seven 24-hour pad tests over 7 consecutive days together with 7 simultaneous fluid and activity charts. The results were analysed collectively and according to urodynamic subsets. Repeatability was assessed by repeated measures analysis of variance and univariate analysis of variance for each urodynamic diagnosis group (USI, mixed and no USI). Variation between pad test weights over the 7 days was low, supporting good repeatability. The number of days of pad testing required to approximate the 7-day average was 3 days. However, a single 24-hour pad test correlated highly with the 7-day average (r=0.881) and was considered sufficient to gauge leakage severity.

Aged↗

Criterion validity, test-retest reliability and sensitivity to change of the St George Urinary Incontinence Score.

OBJECTIVE: To assess the criterion validity, test-retest reliability and the sensitivity to change after treatment of the St George Urinary Incontinence Score (SGUIS). PATIENTS AND METHODS: Women presenting with urinary incontinence completed two SGUIS tests one week apart. A frequency-volume chart (FVC) was completed before the first attendance and the women had a 1-h pad test before treatment. Patients were treated conservatively under the care of a urogynaecologist or nurse continence advisor, or surgically with an open or laparoscopic colposuspension. After treatment, the SGUIS, FVC and 1-h pad test were repeated. RESULTS: The SGUIS correlated moderately well with the number of leaks per week (Spearman's r = 0.610, 95% confidence interval 0.516-0.689, P < 0.001) but less well with the 1-h pad test loss (r = 0.257, 0.124-0.380, P = 0.002). The test-retest reliability was acceptable, as the mean (SD) difference between the first and second SGUIS was 0.337 (2.675), with limits of agreement of -5.012 to -5.686. The change in the SGUIS after treatment correlated well with the improvement in the number of leaks per week (r = 0.742, 0.662-0.805, 156 samples, P < 0.001) but not as well with the change in 1-h pad test loss (r = 0.531, 0.405-0.636, 151, P < 0.001), although the trend was similar. CONCLUSION: The criterion validity of the SGUIS appeared adequate for both the number of leaks per week on the FVC and leakage on the 1-h pad test. The statistical reproducibility of the test was adequate and appeared more responsive to change after treatment than the other measures. The score is suitable for rapid self-administration by patients with a range of incontinence types, unlike most other currently available test instruments.

Adolescent↗

Definition of mild, moderate and severe incontinence on the 24-hour pad test.

The values for 'mild', 'moderate' and 'severe' urinary incontinence have not been determined for the 24-hour pad test. To define these values, a prospective observational study was performed on 110 women with the primary symptom of urinary incontinence. Consenting women performed two 1-hour pad tests one week apart, and seven 24-hour pad tests for seven consecutive days. The 1-hour pad test definitions for mild, moderate and severe were translated to centiles, and used to categorise the 24-hour test values. This revealed that the range for 'mild incontinence' was between 1.3 and 20 g, 'moderate incontinence' ranged from 21 to 74 g, and 'severe incontinence' was defined as 75 g or more in 24 hours. Severity of leakage was analysed in relation to urodynamic diagnosis, age, parity and pelvic floor muscle strength. Increasing severity was associated with increasing age and parity. Women with detrusor overactivity were most likely to have severe leakage. In conclusion, this study defines the three grades of severity for the 24-hour pad test, which may help to guide patients' choice between conservative and surgical treatment and is useful for stratified randomisation of controlled trial participants.

Adult↗

The Contiform incontinence device - efficacy and patient acceptability.

A consecutive series of 59 women with urodynamic stress incontinence but no prolapse were offered treatment with Contiform (available in small/medium/large sizes). The 24-h pad test was the primary outcome measure. Of the 59 enrolled women, 41 (69%) completed the trial protocol. Median use was 21 days (IQR 10-24.5). Two severity groups were categorized based on pretreatment pad testing (mild <30 g/day n=24 patients, 59%) and moderate/severe >30 g/day, n= 17(41%). Overall, loss was reduced by a median of 72% (5-92), p<0.0001, with the greatest reduction seen in the moderate/severe group of 85% (75-100) p<0.0001. No significant benefit on pad testing was noted in the mild group. Both groups showed significant benefit on the Incontinence Impact Questionnaire. The insertion technique was quickly learnt and the device well tolerated. A medium-sized Contiform was used by 33 (80%) women. No serious adverse events occurred.

Adult↗

Is objective cure of mild undifferentiated incontinence more readily achieved than that of moderate incontinence? Costs and 2-year outcome.

Because the prognostic value of 1-h pad testing has received scant attention, we tested the hypothesis that mild incontinence of any etiology is more readily cured than moderate incontinence. A consecutive series of 150 patients with mild (2-9.9 g) to moderate (10-49.9 g) incontinence (as judged by weight gain on 1-h pad testing) [1] attending a urogynecology unit were recruited, of whom 145 completed all baseline objective measures: 110 completed 12 weeks of conservative therapy, with follow-up data at 2 years available for 51 subjects. At 12 weeks 81% of 'mild' patients became 'dry' on the 1-h pad test versus 36.8% in the moderate group (chi2<0.0001). Interestingly the post-treatment changes seen in all other outcomes demonstrated equally positive responses for the mild and moderate groups. At 2-year follow-up 29/71 (40.8%) of patients with mild incontinence and 22/74 (29.7%) of patients with moderate incontinence were satisfied and had no requirement for further therapy, the remainder having sought other treatments (chi2=1.963 P=0.161). Of the responders, (11/29) (37.9%) of mildly incontinent patients and (8/22 (36.4%)) of moderately affected subjects remained continent (on 20-point incontinence score < or =2 m, chi2=0.013, P=0.9087). Improvements in quality of life persisted to an equal degree in both groups.

Aged↗

The 24-hour pad test in continent women and men: normal values and cyclical alterations.

OBJECTIVE: To obtain control values for the 24-hour pad test in a wide age range of continent women using accurate weighing scales and to compare the results obtained from pantyliners and pads in women and men. DESIGN: Prospective anonymous study. SETTING: A Sydney Tertiary Urogynaecology Unit. POPULATION: One hundred and forty continent women and 14 continent men. METHODS: A 24-hour pad test was performed in 120 continent women of widely varying ages, in whom hormonal status and exercise habits were documented. These continent women wore a standardised pantyliner for 24 hours and a high precision beam balance (accuracy 0.1 g) was used to measure the loss on the pad. To assess any variation in pad weights with differing pads, 20 female volunteers undertook the 24-hour test firstly with pantyliners then larger pads. To understand evaporative qualities of the two types of pads, one male wore each type of pad, instilled with 5 mL normal saline for eight hours overnight. Furthermore, to understand the contribution of vaginal secretions, a group of male volunteers performed a 24-hour test with pantyliners followed by pads. MAIN OUTCOMES MEASURES: Pad weight, with regard to hormonal status, exercise, pad type and gender. The median age of subjects was 48 (interquartile range [IQR] 32-60), with a median pad weight gain of 0.3 g (IQR 0.2-0.6; 95th centile 1.3 g). Subgroup analysis showed no significant trends for pad loss in relation to menopause status, use of hormone replacement therapy or hormonal contraception and exercise status during the 24-hour period. Control values for pantyliners were not significantly different from those for continence pads. In addition, normal values in 14 males showed similar results, regardless of pad type. CONCLUSIONS: The response rate of 39% might limit the applicability of the results. However, our finding that women lose only 0.3 g of vaginal secretions in 24 hours is much lower than previously reported. This might arise from the use of a highly accurate beam balance and the recruitment of a large sample of women with widely varying ages. This result might lower the threshold for objective diagnosis of urinary incontinence and alters the pad test definition of 'cure'.

Adult↗

Randomised controlled trial of nurse continence advisor therapy compared with standard urogynaecology regimen for conservative incontinence treatment: efficacy, costs and two year follow up.

OBJECTIVE: To compare the efficacy and labour costs of nurse continence advisors and urogynaecologists in conservative management of urinary incontinence. DESIGN: Single centre randomised controlled trial of patients with mild or moderate leakage. SETTING: Tertiary urogynaecology unit. SAMPLE: One hundred and forty-five consecutive patients with stress and/or urge incontinence. METHODS: Standardised conservative therapy regimens, provided by nurse continence advisors and urogynaecologists. MAIN OUTCOME MEASURE: One-hour pad test, frequency volume charts, a 20-point incontinence score and two quality of life tests, staff treatment times and costs. RESULTS: Of 110 women who completed 12-week treatments, 64% of the women in the nurse continence advisor group (n = 58) and 52% of women treated by urogynaecologists (n = 52) were asymptomatic (dry pad test; OR 1.63, 95% CI 0.71-3.75). There was no significant difference between clinician groups for change in pad test result (P = 0.71), voids/day (0.43), incontinence score (P = 0.57) or quality of life scores (urogenital distress inventory, P = 0.27; Incontinence Impact Questionnaire, P = 0.41). Despite the expected longer consultation times for the advisor group (median 160 min, interquartile range [IQR] 130-210) versus the urogynaecologist group (median 90 min, IQR 60-120), the per capita labour cost for advisor treatment (median AU$59.20, IQR 48.10-77.70) was lower than for treatment given by urogynaecologists (median cost AU$ 189.70, IQR 120.60-250.70, Mann-Whitney U test, P < 0.0001). At 2.5 years, 23/58 patients (40%) treated by advisor and 27/52 patients (52%) treated by urogynaecologist group, who had been cured and discharged, were available for contact. Of these, 29% of women in the nurse continence advisor group and 41% of those treated by urogynaecologists remained continent (on 20-point score). Quality of life improvement persisted equally in both groups. These data should be interpreted cautiously due to a 24% dropout rate. CONCLUSIONS: The reduction in urine leakage and improvement in quality of life observed in patients treated by nurse continence advisors and urogynaecologists were similar at 12 weeks and 2 years, but lower costs arose from treatment provided by nurse advisors. We suggest that conservative treatment by the nurse continence advisor could be used more widely in mild to moderate incontinence.

Aged↗

Insulin increases the intracellular concentration of total oxalyl thiolesters in BC3H-1 myocytes: potential anti-insulin mediators.

Oxalyl thiolesters (RS-CO-COOH) may represent negative intracellular messengers for insulin action. Using a reverse-phase, ion-pair high pressure liquid chromatographic technique, total intracellular oxalyl thiolesters were measured in insulin-sensitive BC3H-1 myocytes after the addition of insulin. The total oxalyl thiolester concentration increased to a maximum of 2.9 times the basal concentration by 30 min after the addition of 100 microU/ml insulin and decreased to 1.8 times by 180 min. Insulin's stimulation of pyruvate dehydrogenase as measured by lactate oxidation ([1-14C]-lactate --> 14CO2) in intact BC3H-1 myocytes reached a maximum at 15-30 min and returned to basal activity during the 60-90 min measurement interval. These results suggest that oxalyl thiolesters are increased in concentration following insulin-induced signal transduction to reverse insulin-stimulated metabolic events.

Animals↗

Loss of purinergic P2X(3) and P2X(5) receptor innervation in human detrusor from adults with urge incontinence.

Activation of purinergic P2X receptors associated with the parasympathetic nerves that supply the human bladder smooth muscle (detrusor) is implicated in control of detrusor contractility. The relative abundance of all seven subtypes colocalized with synaptic vesicles on parasympathetic nerves was examined in specimens from normal adult bladder, infants, and in adults with overactive detrusor contractility and a diagnosis of idiopathic detrusor instability (IDI) to determine whether receptor distribution varied with age or in patients with incontinence. Alteration in control of detrusor innervation was examined with P2X subtype-specific antibodies and an antibody against synaptic vesicles, using immunofluorescence and confocal microscopy. Detrusor samples were taken from: controls, at cystectomy for cancer or cystoscopic biopsy for hematuria (n = 22; age 33-88), child bladder, at surgical correction of vesico-ureteric reflux (n = 21; age 4 months to 2 years), and adults with detrusor instability at cystoscopy-cystodistension (n = 18; age 30-81). Adult specimens contained muscle with large varicosities (1.2 microm) along parasympathetic nerves with colocalized patches of all P2X(1-7) subtypes. Infant bladder revealed little evidence of P2X at age <9 months but approached adult levels at 2 years. Detrusor from IDI patients revealed selective absence of P2X(3) and P2X(5) beneath all the varicosities. This specific lack of P2X(3) and P2X(5) may impair control of detrusor contractility and contribute to the pathophysiology of urge incontinence.

Adult↗

Use of the Dowell Bryant Incontinence Cost Index as a post-treatment outcome measure after non-surgical therapy.

The aim of this study was to use the previously validated Dowell Bryant Incontinence Cost Index (DBICI) as a post-treatment outcome measure after non-surgical therapy and to determine whether the magnitude of reduced leakage would correlate with the magnitude of reduced personal cost. A simple urethral occlusive device (Femassist) was employed in 57 women with stress, urge, or mixed incontinence for 1 month. The DBICI was administered at baseline and after device use, along with a visual analogue scale (VAS) for severity of incontinence impact, a 3-day frequency volume chart (FVC) that documented leaks per 24 hours and pad usage, a 1-hour ICS pad test at standard volume, and two disease-specific quality of life measures (Urogenital Distress Inventory [UDI] and Incontinence Impact Questionnaire [IIQ]). The severity of leakage was significantly reduced on all parameters, and the median personal costs of incontinence fell from AU$6.52 per week (IQR 1.50-10.59) to a median of AU$ 1.57 per week (IQR 0-4.89). A significant correlation (Kendall's rank, tau) was observed between reduction in personal costs and reduction in VAS (tau = 0.24, P= 0.01), leaks/day (tau = 0.20, P = 0.03), pad test loss (tau = 0.29, P = 0.002), and quality of life scores (UDI, tau = 0.23, P = 0.01; IIQ, tau = 0.26, P = 0.005). The personal costs subset of the DBICI appears to be a useful outcome measure for urinary incontinence research and could be widely employed to assess the impact of continence treatments on the patient's economic burden.

Aged↗

Thymoma: trends over time.

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.

Adult↗

Surgical resection for pulmonary metastases from colorectal cancer.

BACKGROUND: Isolated pulmonary metastases from colorectal cancer are rare. The present study reports on the 15-year experience of the Royal Prince Alfred Unit and discusses means of improving survival outcomes. METHODS: This was a retrospective review, over a 15-year period, of 41 patients who had resectable pulmonary metastases of colorectal origin. RESULTS: Most were asymptomatic at the time of diagnosis. Seventy-two per cent had solitary metastases. The most common procedure performed was a lobectomy. Median follow up was 21 months. Five-year survival was 24%. There were no significant prognostic indicators except for the ability to achieve clear surgical margins. CONCLUSION: Morbidity and mortality have not altered significantly over time. But an improved selection process such as the use of preoperative positron emission tomography will potentially improve survival outcomes.

Adenocarcinoma↗

Adenocarcinoma of the rat esophagus in the presence of a proton pump inhibitor: a pilot study.

This study examines the effects of a proton pump inhibitor on a rat model of duodenogastric reflux. Duodenoesophageal reflux was induced in 60 rats by performing a duodenesophagostomy. The study group received daily intraperitoneal injections of a proton pump inhibitor for 6 months and the control group received an equivalent injection of saline. Rats were examined at death for macroscopic tumor, dysplasia, adenocystic changes, papillomatosis, and adenocarcinoma. Five out of 19 rats in the study group and three out of 20 rats in the control group developed dysplastic/adenocarcinomatous changes. Ten of the rats in the study group died before the end of the study, as opposed to one in the control group (this is not statistically significant). There was no difference in the number of cancers that developed in the two groups. However, there was an insignificant trend to earlier appearance of detectable disease in the study group.

Adenocarcinoma↗

Inadequate repeatability of the one-hour pad test: the need for a new incontinence outcome measure.

OBJECTIVE: To assess the reproducibility of two one-hour pad tests performed within one week using serial ultrasound scanning to obtain identical bladder volumes, and to measure the effect of patient anxiety upon test reproducibility. DESIGN: Prospective observational study. SETTING: Tertiary urogynaecological unit. SAMPLE: Fifty-six incontinent women undergoing 112 pad tests. METHOD: Two one-hour pad tests were performed with natural diuresis one week apart prior to treatment. At the second test, serial ultrasound scans were performed until bladder volume reached that of the first test, followed by identical provocation. MAIN OUTCOME MEASURES: One-hour pad loss, bladder volumes (Vol1, Vol2), anxiety VAS questionnaire. RESULTS: Despite serial scanning, bladder volumes differed significantly. Median volume before second pad test was 541 mL, compared with 433 mls before first test (P < 0.001). The second pad test was also significantly larger than first (median 16g vs 4g, P = 0.017), and 13/56 (23%) women were dry on the first test but incontinent on the second. In 26 women (46%) both bladder volumes were similar, but the second pad loss was still significantly greater (median 14g vs 4g, P = 0.037). The mean difference between tests was 10g and the limits of agreement were wide (ranging from -44 to +66 g difference for the test result). Women were more anxious about leaking during the first test (Median VAS during the first test was 2.8cm, compared with 0.6cm during the second test, P = 0.008). 42.5% found the second test to be more typical. CONCLUSION: In women with similar bladder volumes, the test-retest reliability of the one-hour pad test was judged to be clinically inadequate, as the first and second pad test could differ by -44 to +66g. Lower anxiety levels at the second test may account for this finding. The one-hour pad test is a useful baseline measure of incontinence, but the poor repeatability suggests that is not an optimal measure of post-treatment change.

Anxiety↗

Metabolic disposition and pharmacokinetics of [14C]-amprenavir, a human immunodeficiency virus type 1 (HIV-1) protease inhibitor, administered as a single oral dose to healthy male subjects.

The objective of this study was to determine the metabolic profile, routes of elimination, and total recovery of amprenavir and its metabolites after a single oral dose of [14C]-amprenavir. Six healthy male subjects each received a single oral 630 mg dose of amprenavir containing 95.76 microCi of [14C]-amprenavir in this Phase I mass balance study. The metabolic disposition of amprenavir was determined through analyses of radiocarbon in whole blood, plasma, urine, and stool samples, collected for a period of 10 to 17 days postdosing. Cerebral spinal fluid (CSF) sampling was conducted on day 1. The ratio of unchanged amprenavir AUC0-->infinity to plasma radiocarbon was 27%, suggesting that most of the radiocarbon was metabolites. The median total recovery of the administered dose of radiocarbon was 89% (range: 66%-93%), with 75% (range: 56%-80%) recovered in the feces and 14% (range: 10%-17%) in the urine. Most of the recovered radiocarbon in the feces and urine was excreted within 240 and 48 hours postdose, respectively. Of the 75% of the radiocarbon dose recovered in the feces, 62% was identified as a metabolite resulting from dioxidation of the tetrahydrofuran ring (GW549445X) and 32% as a metabolite resulting from subsequent oxidation of the p-aniline sulfonate group (GW549444X). Unchanged amprenavir was below the limit of quantitation in feces and urine. Therefore, approximately 94% of the dose excreted in the feces was accounted for by these two metabolites. Concentrations of radiocarbon in the CSF were below the limit of quantitation in 5 of 6 subjects sampled. In summary, oral amprenavir is extensively metabolized in humans, with concentrations of unchanged drug below the limits of quantitation in urine and feces. The majority (75%) of administered radiocarbon was excreted in feces.

Administration, Oral↗

The bioavailability of the novel nonnucleoside reverse transcriptase inhibitor GW420867X is unaffected by food in healthy male volunteers.

The effect of food on the bioavailability of GW420867X, a novel nonnucleoside reverse transcriptase inhibitor, was investigated in 15 young, healthy, male volunteers. A single oral dose of GW420867X 100 mg was administered in the fasted state, after a high-fat meal, and after a meal of normal fat composition. Tolerability and pharmacokinetic sampling were assessed at baseline and up to 600 hours. The median concentration-time plots for each treatment group were essentially superimposable. Neither the rate nor the extent of absorption of GW420867X was significantly affected by food. The median time to peak plasma concentration was 3 to 4 hours, irrespective of treatment. Pairwise comparisons using the fasted treatment as the comparator showed no impact of food on GW420867X pharmacokinetics. GW420867X was well tolerated. There were no serious or treatment-limiting adverse events; all episodes reported were rated as mild to moderate. The bioavailability of GW420867X was unaffected by food. GW420867X may be administered independently of food and fat intake.

Adult↗