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Biomedical subjects

J W Moore

Publications and source records attributed to J W Moore.

At least 55 records · Page 3Linked to original sources

A prospective study of endogenous serum hormone concentrations and breast cancer risk in post-menopausal women on the island of Guernsey.

The associations between serum concentrations of oestradiol, testosterone and sex hormone-binding globulin (SHBG) and risk of breast cancer in post-menopausal women were investigated in a prospective study on the island of Guernsey. Sixty-one women who developed breast cancer an average of 7.8 years after blood collection were matched for age, year of blood collection and number of years post-menopausal with 179 control subjects. Women using exogenous hormones at the time of blood collection were excluded from the study. Women who subsequently developed breast cancer had a 29% higher geometric mean oestradiol concentration than control women (P = 0.004). The odds ratio for breast cancer in the top third compared with the lowest third of the oestradiol concentration distribution was 5.03 (95% confidence interval 2.02-12.49, P for trend < 0.001). Adjusting for testosterone and SHBG concentrations did not substantially alter the odds ratio for oestradiol. Although testosterone and SHBG concentrations were associated with breast cancer risk, the concentrations of these hormones were correlated with those of oestradiol; the associations were not statistically significant after adjusting for oestradiol concentration. These data provide evidence that serum oestradiol concentrations in post-menopausal women may have a substantial effect on breast cancer risk.

Adult↗

Thiolmethyltransferase activity in the human colonic mucosa: implications for ulcerative colitis.

Ulcerative colitis is associated with a selective reduction of n-butyrate oxidation by the colonic epithelial cells although the reason for this has been unclear. Colonic epithelial cell n-butyrate oxidation can be inhibited in vitro by incubation with sulphide but the role of mucosal detoxification of sulphide in the metabolic welfare of the colonic mucosa has not been examined. This study aimed to assess the role mucosal detoxification of sulphide by thiolmethyltransferase (TMT)-mediated methylation may play in protecting the healthy colonic mucosa from the adverse effects of luminal sulphide. Colonic epithelial cell suspensions from healthy human proximal (n = 9) and distal colon (n = 10) were incubated in the presence of 14C-labelled n-butyrate (5 mmol/L) alone, butyrate plus sodium hydrogen sulphide (NaHS) (1.5 mmol/L), or butyrate plus NaHS plus S-adenosyl-methionine 1,4 butane disulphonate (SAMe) (5 mmol/L). Study end points were metabolic performance (14CO2 production) and mucosal TMT activity. Incubation with NaHS induced a significant inhibition of 14CO2 production compared with control incubations (P < 0.001) which was similar for proximal and distal colonic cell suspensions. S-adenosyl-methionine 1,4 butane disulphonate reversed this effect completely in proximal but not in distal cell incubations, suggesting a greater susceptibility of the distal colon to the sulphide effect. Although median whole mucosal TMT values did not differ between proximal and distal colonic mucosa, a non-normal distribution of distal TMT values was observed. However, neither the degree of sulphide inhibition of control 14CO2 production nor the degree to which SAMe reversed this inhibition correlated with whole mucosal TMT activity. The study concluded that regional variation exists in TMT activity in the human colon but whilst methylation appears to protect colonic epithelial cells against sulphide-induced inhibition of n-butyrate oxidation, this cannot be directly correlated with mucosal TMT activity.

Aged↗

Hydrogen sulphide produces diminished fatty acid oxidation in the rat colon in vivo: implications for ulcerative colitis.

BACKGROUND: Several lines of evidence suggest a possible role for reduced forms of sulphur (including sulphide) in ulcerative colitis. The aims of this study were to assess the metabolic profile of colonic epithelial cells after treatment in vivo with hydrogen sulphide and correlate this with mucosal histological appearances. METHODS: Adult Sprague-Dawley rats had antegrade Roux-en-Y colostomies fashioned to allow access to the 'in-flow' bowel. Animals were treated with 2 mL sodium hydrosulphide (10, 20, 30 mmol/L) or saline control twice daily via the stoma for four (acute experiments) and 90 (chronic experiments) days. Isolated colonic epithelial cell suspensions prepared from such animals were incubated in the presence of [1-14C]-labelled n-butyrate (5 mmol/L) or [6-14C]glucose (5 mmol/L). Metabolic performance was measured radiometrically (14CO2 production) and enzymatically (ketone body production and lactogenesis). The histological appearances of treated mucosa were scored for acute inflammatory changes. RESULTS: There was a highly significant reduction in 14CO2 production from both n-butyrate and glucose in all groups compared to the control in both acute and chronic experiments. There was no difference between groups with respect to histological appearance and no evidence of acute inflammation in any specimen. CONCLUSIONS: Sodium hydrosulphide impairs rat colonic epithelial metabolic performance in vivo, but does not produce mucosal inflammation.

Animals↗

Effect of sulphide on short chain acyl-CoA metabolism in rat colonocytes.

BACKGROUND: It has been proposed that the diminished n-butyrate oxidation observed in ulcerative colitis may be the result of sulphide induced inhibition of short chain acyl-coenzyme A (acyl-CoA) dehydrogenase activity. AIM: To examine the acyl-CoA ester profiles in isolated rat colonic epithelial cells treated in vitro with sodium hydrogen sulphide (NaHS). METHODS: Isolated rat colonic epithelial cell suspensions were incubated for 10 minutes in the presence of [1-14C] n-butyrate (5 mM), with and without NaHS (1.5 mM). Incubations were carried out both in the presence and the absence of exogenous CoA and ATP. Metabolic performance was assessed by 14CO2 production and by acyl-CoA ester production measured by HPLC with ultraviolet detection. RESULTS: Results are given as mean (SEM). For colonocytes incubated in the presence of exogenous CoA and ATP, treatment with NaHS significantly diminished 14CO2 production (control 0.97 (0.06) mumol/g dry weight cells/min, treated 0.26 (0.09) mumol/g dry weight cells/min, p = 0.0019), was associated with an increase in butyryl-CoA concentrations in the final reaction mixture at 10 minutes (control 2.55 (0.28) mumol/g dry weight cells, treated 3.32 (0.32) mumol/g dry weight cells, p = 0.002), and a reduction in crotonyl-CoA concentrations (control 0.274 (0.02) mumol/g dry weight cells, treated 0.120 (0.04) mumol/g dry weight cells, p = 0.008). The mean concentration of acetyl-CoA in the reaction mixture at 10 minutes was not significantly different between control and sulphide treated incubations. There were no significant differences in acyl-CoA ester profiles observed when cells were incubated in the absence of exogenous CoA and ATP. CONCLUSIONS: These results support the view that sulphides inhibit n-butyrate oxidation in colonic epithelial cells by inhibiting short chain acyl dehydrogenation of activated fatty acids.

Acyl Coenzyme A↗

Pergolide mesylate. Adverse events occurring in the treatment of cocaine dependence.

In this preliminary report from a placebo-controlled, double-blind, dose-response study on the use of pergolide mesylate for cocaine dependence in outpatients 8 out of 235 subjects noted adverse events requiring breaking of the blind. Events occurred at or within 7 days of receiving the first dose of medication and included side effects (four cardiovascular, one psychiatric); drug-drug interactions (one): and clinical exclusions (two pregnancies). Two anecdotes of illicit abuse are reported. Although efficacy is unestablished, pergolide appears to be safe in the early treatment of cocaine dependence except where there are relative contraindications.

Adult↗

Laparoscopic resection of the colon and rectum for cancer.

BACKGROUND: Laparoscopically-assisted resection for large bowel cancer is technically feasible. Sixty-six patients who had resection of the colon or rectum for cancer have been audited prospectively. METHODS: Clinical and pathological data were collected prospectively as part of the ongoing Concord Hospital colorectal cancer project. Patients were followed up for a median of 29 months. RESULTS: In 57 of 66 patients in whom laparoscopic resection was attempted the operation was completed laparoscopically. Three patients died from perioperative myocardial infarction. The median postoperative stay was 14 days. There was a high incidence of postoperative respiratory and cardiac complications. One patient developed a port-site metastasis. CONCLUSION: There was no obvious benefit from laparoscopically-assisted resection of large bowel cancer in these patients.

Aged↗

Prostheses, orthoses, and shoes for partial foot amputees.

A variety of devices are available for aftercare of the partially amputated foot. The prescription of these devices depends on the extent of the amputation, subsequent muscle balance, and the willingness of the patient to comply with the use of the device. Above all, long-term follow-up care is necessary to evaluate the need and effectiveness of any orthotic prescription as well as to provide local care for excessive preulcerative keratosis associated with new focal pressure points.

Amputation, Surgical↗

Comparison of results of stent implantation in small (<20 kg) children versus larger children with pulmonary artery stenoses.

We compared the results of stent implantation for pulmonary artery stenoses in patients weighing <20 kg (group 1, 17 patients, 21 stents) versus those weighing > or = 20 kg (group 2, 11 patients, 13 stents). There was no significant difference in the mean percent increase in diameter or mean percent gradient reduction acutely and at short-term follow-up between group 1 and 2 patients.

Adolescent↗

Toward quality assurance for metaphase FISH: a multicenter experience.

Although fluorescent in situ hybridization (FISH) is rapidly becoming a part of clinical cytogenetics, no organization sponsors multicenter determinations of the efficacy of probes. We report on 23 laboratories that volunteered to provide slides and to use a probe for small nuclear ribonucleoprotein polypeptide N (SNRPN) and a control locus. Experiences with FISH for these laboratories during 1994 ranged from 0 to 645 utilizations (median = 84) involving blood, amniotic fluid, and bone marrow. In an initial study of hybridization efficiency, the median percentage of metaphases from normal individuals showing two SNRPN and two control signals for slides prepared at each site was 97.0 (range = 74-100); for slides prepared by a central laboratory, it was 97.8 (range = 81.6-100). In a subsequent blind study, each laboratory attempted to score 5 metaphases from each of 23 specimens [8 with del(15)(q11.2-->q12) and 15 with normal #15 chromosomes]. Of 529 challenges, the correct SNRPN pattern was found in 5 of 5 metaphases in 457 (86%) and in 4 of 5 in 33 (6%). Ambiguous, incomplete, or no results were reported for 32 (6%) challenges. Seven (1%) diagnostic errors were made, including 6 false positives and 1 false negative: 1 laboratory made 3 errors, 1 made 2, and 2 made 1 each. Most errors and inconsistencies seemed due to inexperience with FISH. The working time to process and analyze slides singly averaged 49.5 min; slides processed in batches of 4 and analyzed singly required 36.9 min. We conclude that proficiency testing for FISH by using an extensive array of challenges is possible and that multiple centers can collaborate to test probes and to evaluate costs.

Autoantigens↗

Toward quality assurance for metaphase FISH: a multi-center experience.

Although fluorescent in situ hybridization (FISH) is rapidly becoming a part of clinical cytogenetics, no organization sponsors multi-center determinations of the efficacy of probes. We report on 23 laboratories that volunteered to provide slides and to use a probe for SNRPN and a control locus. Experiences with FISH for these laboratories during 1994 ranged from 0 to 645 utilizations (median = 84) involving blood, amniotic fluid and bone marrow. In an initial study of hybridization efficiency, the median percentage of metaphases from normal individuals showing two SNRPN and 2 control signals for slides prepared at each site was 97.0 (range = 74-100); for slides prepared by a central laboratory, it was 97.8 (range = 81.6-100). In a subsequent blind study, each laboratory attempted to score 5 metaphases from each of 23 specimens [8 with del(15) (q11.2-->q12) and 15 with normal 15 chromosomes]. Of 529 challenges, the correct SNRPN pattern was found in 5 of 5 metaphases in 457 (86%) and in 4 of 5 in 33 (6%). Ambiguous, incomplete or no results were reported for 32 (6%) challenges. Seven (1%) diagnostic errors were made including 6 false positives and 1 false negative: 1 laboratory made 3 errors, 1 made 2, and 2 made 1 each. Most errors and inconsistencies seemed due to inexperience with FISH. The working time to process and analyze slides singly averaged 49.5 minutes; slides processed in batches of 4 and analyzed singly required 36.9 minutes. We conclude that proficiency testing for FISH using an extensive array of challenges is possible and that multiple centers can collaborate to test probes and to evaluate costs.

Humans↗

Morbidity and mortality following laparoscopic-assisted right hemicolectomy for cancer.

PURPOSE: This study was undertaken to compare morbidity, mortality, and pathology after laparoscopically assisted right hemicolectomy (LARHC) or open right hemicolectomy (ORHC) for cancer of the right colon. METHODS: Patients undergoing either LARHC or ORHC for invasive carcinoma of the right colon during a 30-month period were studied. Data were collected from two sources. All morbidity, mortality, and pathology data were collected prospectively in a form suitable for computer storage and analysis as part of the ongoing Concord Hospital Colorectal Cancer Registry. Data concerning in hospital course were obtained by casenote review. RESULTS: Twenty-eight patients underwent LARHC, and 33 had an ORHC during the study period. The two groups were well matched with respect to age, sex, weight, associated comorbidities, and tumor stage. Mean operating room use time was significantly higher for LARHC (LARHC = 261 minutes; ORHC = 203 minutes; P < 0.001). Mean hospital stay from date of resection was the same in both groups (LARHC = 12 days; ORHC = 12.2 days). There was no significant difference between procedures with respect to postoperative complications, return of gastrointestinal function, or narcotic analgesic requirements. There was a significant shorter distal margin of resection in the LARHC group (ORHC = 13.4 cm; LARHC = 10 cm; P = 0.03). Total cost was significantly greater for LARHC ($9,064 vs. $7,881 (Australian); P < 0.001). Median follow-up was 23.4 months for the LARHC group and 23.9 months for the ORHC group. To date, there have been no local or port site recurrences. CONCLUSION: Although there is no difference in morbidity and mortality following LARHC or ORHC, there is no apparent benefit for LARHC.

Aged↗

Aortopulmonary collateral vessels and prolonged pleural effusions after modified Fontan procedures.

Pleural effusions after the modified Fontan procedure are unpredictable, increase morbidity, and prolong hospital stay. To assess the relation between preoperative characteristics and postoperative pleural drainage, we performed a retrospective study of 71 patients who underwent Fontan procedures. Analyses revealed no significant relation between duration of effusion and age at Fontan, preoperative oxygen saturation, pulmonary artery pressure, ventricular end-diastolic pressure, type of Fontan, or prior cavopulmonary anastomosis. Patients with significant aortopulmonary collateral vessels evidenced by angiographic opacification of the pulmonary arteries or veins had more prolonged pleural drainage. The duration of the pleural drainage was significantly less in patients who had aortopulmonary collateral occlusion.

Adolescent↗

A case-control study of cryptorchidism and maternal hormone concentrations in early pregnancy.

Serum samples taken between 6 and 20 weeks of gestation were obtained from 28 mothers who gave birth to cryptorchid sons (cases) and from 108 control mothers. In comparison with controls the cases had 10% higher geometric mean oestradiol (95% CI -13% to +39%: P=0.42) and 10% lower geometric mean testosterone (95% CI -27% to +10%: P=0.30). Among the samples collected between 6 and 14 weeks of gestation geometric mean concentrations of oestradiol and testosterone were 5% lower (95% CI -32% to +31%: P=0.74) and 25% lower (95% CI -45% to +1%: P=0.06) respectively in cases than in controls. Among the samples collected between 15 and 20 weeks of gestation geometric mean concentrations of oestradiol and testosterone were 29% higher (95% CI -8% to +79%: P=0.14) and 21% higher (95% CI -8% to +60%: P=0.18) respectively in cases than in controls. The results do not support the hypothesis that cryptorchidism may be caused by high concentrations of oestradiol in the maternal blood during the first phase of testicular descent, but suggest that the possible association of cryptorchidism with low maternal testosterone during early gestation should be further investigated.

Adult↗

A prospective study of urinary oestrogen excretion and breast cancer risk.

To test the hypothesis that high levels of endogenous oestrogens increase the risk for developing breast cancer, concentrations of oestrone, oestradiol and oestriol were measured in 24 h urine samples from 1000 women participants in a prospective study of breast cancer on the island of Guernsey. Sixty-nine subjects were diagnosed with breast cancer subsequent to urine collection. Among women who were premenopausal at the time of urine collection, cases excreted less oestrogen than controls; the odds ratios (95% CI) for breast cancer in the middle and upper thirds of the distribution of oestrogen excretion, in comparison with the lower third (reference group, assigned odds ratio = 1.0), were 0.5(0.2-1.2) and 0.4(0.2-1.1) respectively for oestrone, 0.8(0.4-1.8 and 0.4(0.2-1.1) for oestradiol, 0.7(0.3-1.6) and 0.7(0.3-1.6) for oestriol and 0.9(0.4-2.0) and 0.5(0.2-1.3) for total oestrogens. Among women who were post-menopausal at the time of urine collection, the trend was in the opposite direction, with an increase in risk associated with increased oestrogen excretion; the odds ratios were 0.9(0.3-2.2) and 1.1(0.5-2.8) for oestrone, 0.8(0.3-2.3) and 1.9(0.8-4.6) for oestradiol, 1.5(0.6-3.9) and 1.8(0.7-4.6) for oestriol and 0.9(0.4-2.6) and 1.9(0.7-4.7) for total oestrogens. The trends of increasing risk with increasing oestrogen excretion among post-menopausal women were statistically significant for oestradiol (P = 0.022) and for total oestrogens (P = 0.016). We conclude that high levels of endogenous oestrogens in post-menopausal women are associated with increased breast cancer risk, but that the relationship of oestrogens in premenopausal women with risk is unclear.

Adult↗

Tetralogy of Fallot repair results in activation of the renin-angiotensin-aldosterone system.

Fluid retention is a common problem following transannular patch repair of tetralogy of Fallot. The present study was undertaken to evaluate whether humoral substances may contribute to this process. Patients undergoing tetralogy of Fallot repair using a transannular patch technique were compared to patients undergoing simple ventricular septal defect repair. Hormone levels were determined by radioimmunoassay. Fluid retention was defined as pleural effusions persisting beyond 5 days. The data demonstrate that patients undergoing tetralogy of Fallot repair had elevated levels of anti-diuretic hormone, renin, angiotensin II, and aldosterone as compared to a group with ventricular septal defect. The elevation in hormone levels in the tetralogy of Fallot group was principally accounted for by those who developed effusions postoperatively. These results suggest that activation of the renin angiotensin-aldosterone system may be one of the contributing factors to fluid retention following tetralogy of Fallot repair.

Aldosterone↗

A modification of single stapled colorectal anastomosis using the transanal insertion device (TAIS).

A modification of single stapled colorectal anastomosis utilizing a reusable stapler head (transanal insertion device [TAIS]) is described. This modification minimizes the time that the proximal bowel is open by allowing early placement of the circular stapler head, and minimizes the risk of rectal injury that may be associated with the passage of a circular stapling device without the head in situ.

Anastomosis, Surgical↗