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Biomedical subjects

J E Roulston

Publications and source records attributed to J E Roulston.

At least 19 recordsLinked to original sources
PubMed2002

Screening with tumor markers: critical issues.

Reviewing the literature it would appear that tumor markers have often flattered to deceive. Early promise does not often seem to be borne out in extended trials. Despite apparently high specificity, very few markers are capable of assisting in a screening process. This brief review attempts to put the roles of tumor markers in perspective and explain how their misapplication has led to misunderstanding of their potential value in a clinical context. It also considers the theoretical basis for their use and highlights how misunderstanding of these can lead to flawed studies and application.

Biomarkers, Tumor↗
PubMed1999

Serum amylase isoenzymes in patients undergoing operation for ruptured and non-ruptured abdominal aortic aneurysm.

OBJECTIVE: Previous work has suggested that hyperamylasemia in patients who undergo operation for ruptured abdominal aortic aneurysm (AAA) is associated with poor outcome. The aims of this study were to determine, for the first time, the source of serum amylase in such patients and to examine the prognostic significance of amylase isoenzyme expression. METHODS: This study was designed as a prospective clinical and laboratory study. The study consisted of 40 patients who underwent operation for ruptured AAA and 10 patients who underwent operation for non-ruptured AAA. The main outcome measures were serum total and pancreatic and salivary amylase activities determined with enzymatic colorimetric assay before operation and 6 hours after aortic clamp release. RESULTS: Five of 40 patients (12.5%) with rupture and one of 10 patients (10%) with non-rupture had elevated total amylase levels before operation, and seven of 31 patients (23%) with rupture and five of 10 patients (50%) with non-rupture had elevated total amylase levels after operation. The preoperative salivary amylase (P =.05) and postoperative pancreatic amylase (P <.02) levels were significantly lower in ruptured AAA as compared with non-ruptured AAA. The preoperative salivary amylase level was significantly lower in non-survivors of rupture, such that a level equal to or less than 45 U/L was associated with death in 11 of 13 patients (85%). CONCLUSION: These data do not support previous works that suggest that hyperamylasemia is associated with poor outcome in ruptured AAA. By contrast, a low preoperative salivary amylase level was associated with increased mortality in ruptured AAA and may be a marker of the severity of shock.

Aged↗
PubMed1993

The value of the human milk fat globule membrane antigen HMFG2 in epithelial ovarian cancer monitoring: comparison with CA125.

We assayed serum HMFG2 in serial samples from 215 primary epithelial ovarian cancer patients using an 'in-house' single determinant ELISA, 45% of patients with stage I, 54% with stage II, 61% with stage III and 75% with stage IV disease had elevated serum HMFG2. Post-operative levels were significantly related with residual tumour volume (P < 0.005), and fell in the majority of responders, although the association with response to first-line chemotherapy was not significant. HMFG2 had a sensitivity of 50% specificity of 83%, accuracy of 61%, PVP of 86% and PVN of 45% for disease at second-look laparotomy. Serial levels gave a lead time to clinical relapse in 47% of patients who responded to therapy, including one patient with negative CA125 levels. HMFG, paralleled CA125 in many respects, although it was elevated in fewer patients. In a stepwise discriminant analysis, HMFG2 added to the discrimination of CA125 (r = 0.183, P < 0.005), although additional accurate information was only given in patients with advanced poorly differentiated serous cystadenocarcinoma. Given that HMFG2 is expressed in few patients who are CA125 negative it is unlikely that it will have a significant clinical impact upon patient management.

Antibodies, Monoclonal↗
PubMed1993

The prognostic value of early CA125 serum assay in epithelial ovarian carcinoma.

We examined the prognostic value of early serum CA125 assay in 58 patients with advanced epithelial ovarian cancer together with residual disease, age, tumour grade, performance status, and the presence of ascites or adhesions at primary surgery. CA125 was a highly significant predictor of both progression free and overall survival after the first cycle and throughout primary chemotherapy. After the first cycle, CA125 was by far the most significant predictor of progression free survival (P < 0.0005). At this time, CA125 was a highly significant predictor of survival (P < 0.005), but did not add to performance status (P < 0.001) in multivariate analysis. We were able to identify three statistically-distinct prognostic groups. Patients in the upper quartile, with CA125 levels greater than 450 U ml-1, had a very poor median survival of 7 months. Patients in the lower quartile, with CA125 levels less than 55 U ml-1 had a good median survival of 23 months. Those in the two interquartile groups, who had CA125 levels ranging from 58-221 U ml-1 and 228-434 U ml-1, had relatively intermediate median survival times of 16 months and 15 months respectively. Although CA125 levels provided significant prognostic information, in the majority of patients CA125 merely confirmed overall clinical impression.

Adult↗
PubMed1993

Serological markers for metastatic breast cancer.

Three serum markers, TPS, CA 15.3 and CEA, were used to monitor the response to treatment of 20 patients with metastatic breast cancer. At the time of the first evidence of metastases or at the time of progression of known metastatic disease, 84% of TPS values were above the reference limit, as compared to 74% for CA 15.3 and 84% for CEA. If the treatment instituted was effective, 60% of TPS values showed an early (within 2 or 3 weeks after commencement or change of therapy) reduction in level against only 27% of CA 15.3 and 27% of CEA levels. This suggests that TPS provides a more sensitive and earlier predictor of therapeutic response. In patients with clinical evidence of further progression of disease while on therapy, 86% of TPS values showed persistent elevation or increase, as compared to 71% of CA 15.3 levels and only 36% of CEA levels. It was also noted in these patients that TPS values rose earlier than either CA 15.3 or CEA. This indicates that TPS is a more reliable predictor of response to treatment than the other two markers. In addition, we found that, at the time of presentation, in women who had visceral metastases (liver, lung, or brain alone or in combination), 87% of TPS values were raised, as compared to 80% of CA 15.3 and 73% of CEA values. In women who had bone and soft tissue metastases at presentation, 75% of TPS values were elevated, against 50% of CA 15.3 and 75% of CEA values.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

Measurement of placental alkaline phosphatase activity in benign and malignant pleural effusions.

The usefulness of placental alkaline phosphatase (PLAP) as a diagnostic marker of malignancy was assessed in pleural fluid from 60 patients with effusions. Pleural fluid PLAP activities were measured by an enzyme linked immunoassay (ELISA) using the two monoclonal antibodies H17E2 and H317. Similar values were found in groups of patients with primary bronchial tumours (n = 12), secondary malignancies (n = 23), and "benign" conditions (n = 25). The highest values were found in a small subgroup of patients with metastatic ovarian carcinoma. However, the production of this enzyme by normal lung makes the measurement of PLAP in pleural fluid unhelpful as a diagnostic aid to distinguish "benign" from malignant effusions.

Alkaline Phosphatase↗
PubMed1989

Vasopressin secretion in diabetic subjects with and without autonomic neuropathy: responses to osmotic and postural stimulation.

1. The release of arginine vasopressin (AVP) after an osmotic stimulus and head-up tilt was assessed in diabetic subjects with and without autonomic neuropathy. 2. Six diabetic subjects with (DAN +ve) and five without (DAN -ve) evidence of autonomic neuropathy and five normal subjects were infused with 5% (w/v) NaCl at a rate of 0.05 ml min-1 kg-1 body weight for 120 min. Blood pressure, heart rate and plasma AVP were measured over this period. 3. Seven DAN +ve, six DAN -ve and six normal subjects were tilted head-up to 45 degrees for 120 min. Blood pressure, heart rate and plasma AVP were measured during the study. 4. Infusion of 5% (w/v) NaCl produced appropriate rises in plasma osmolality and plasma AVP levels which did not differ between the three groups, confirming the normal osmotic release of AVP in the diabetic subjects. 5. During head-up tilt, there were no differences in AVP responses between the three groups, despite a major hypotensive stimulus in the DAN +ve group. 6. We conclude that osmotic release of AVP is normal in diabetes, but that cardiovascular release of AVP is impaired in diabetic subjects with cardiovascular reflex evidence of autonomic neuropathy, reflecting an afferent defect.

Adult↗
PubMed1989

Serum placental-like alkaline phosphatase (PLAP): a novel combined enzyme linked immunoassay for monitoring ovarian cancer.

A new combined enzyme linked immunoassay (ELISA) was developed to measure both serum placental-like alkaline phosphatase (PLAP) activity (PLAPA) and concentration (PLAPC) in the same microtitre plate using an Imperial Cancer Research Fund monoclonal antibody, designated H17E2. PLAP A and PLAP C were determined together with an existing marker, CA125 in 397 serial samples from 87 patients with epithelial ovarian cancer. Retrospective assessment showed the sensitivity to increase from 73% with CA125 alone, to 88% using CA125 and PLAP A, and to 93% with all three markers in 261 samples from the patients with known active disease at the time of sampling. When the results for all 397 samples were included in the analysis, however, the specificity, sensitivity, accuracy and predictive powers of this monoclonal antibody were not sufficiently high to assist in the prospective follow up of patients with ovarian cancer. This was due to a significant number of false positive and false negative results. Our data indicate that PLAP A or PLAP C estimation with H17E2 may, therefore, only be of value in the management of those patients with known active disease who are already known to be "marker positive" for this antigen.

Adenocarcinoma↗
PubMed1987

Studies with an automated kinetic assay for plasma angiotensin-converting enzyme activity and its potentiation by zinc ion.

Measurement of plasma angiotensin-converting enzyme (ACE) is of value in sarcoidosis and, when specific inhibitors are prescribed therapeutically, in hypertension and heart failure. In this study a rapid kinetic assay for estimation of plasma ACE is described and assessed. In particular the effects of zinc ion have been studied. In contrast to previous reports, a marked potentiation of ACE activity by micromolar concentrations of zinc was noted. The relationship between plasma zinc concentration and ACE activity in vivo was also investigated and related to albumin concentration. The findings may have implications for interpretation of plasma ACE activity in patients with low plasma zinc levels.

Animals↗
PubMed1987

Effect of the partial beta-agonist prenalterol on plasma renin activity in patients with left ventricular failure.

Beta agonist therapy for heart failure has been disappointing, perhaps because of renin induced aldosteronism. To investigate this possibility we measured plasma renin activity (PRA) in 23 patients (17 male, 6 female, age 41-70) with New York Heart Association stage III heart failure due to ischaemic heart disease in a placebo controlled trial over one month. All patients received constant doses of digoxin and diuretics throughout the trial. Compliance was confirmed in all patients by digoxin and prenalterol assay. In a preliminary (dose titration) study of 9 patients there was a progressive, but non-significant rise of mean PRA from 14.8 to 17.6 and 27.7 ng/ml per h with doses of 20, 50 and 100 mg of prenalterol, respectively. After one month of treatment with prenalterol (n = 11), PRA was 12.8 +/- 2.4 (SEM) ng/ml per h which was not significantly different from the initial level of 14.4 +/- 2.3 ng/ml per h (n.s.). The placebo group (n = 12) results were 13.8 +/- 4.2 ng/ml per h at entry and 14.4 +/- 5.2 ng/ml per h at one month (n.s.). These results indicate that PRA is elevated by acute treatment with the partial beta agonist prenalterol but stimulation of renin secretion does not appear to occur with chronic therapy.

Adult↗
PubMed1987

Why is plasma angiotensin-converting enzyme activity elevated in hyperthyroidism?

The elevation in plasma angiotensin-converting enzyme (ACE) levels observed in patients with hyperthyroidism is unexplained. In this study three hypotheses were investigated. Results from a study using rats treated with thyroid hormones indicated that the increased ACE was not due to increased cleavages of enzyme from lung endothelia. Data from patients with specific tissue damage argue against a nonspecific release of ACE from damaged cells. Data from cultured cell experiments, however, strongly support a direct effect of thyroid hormones upon ACE synthesis and secretion.

Animals↗