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Biomedical subjects

C Selby

Publications and source records attributed to C Selby.

At least 19 recordsLinked to original sources
PubMed2000

Measurement of urinary free cortisol using the Acs:180 serum cortisol chemiluminescent immunoassay.

Measurement of urinary free cortisol using the Bayer Automated Chemiluminescent System (ACS:180 PLUS) was evaluated and compared with an in-house extraction radioimmunoassay (RIA). Inter-assay coefficients of variation were acceptable, being respectively 5.3%, 4.8% and 3.8% at 141, 406 and 942 nmol/L (n=20) for the ACS direct assay and 19.4% and 12.1% at 27 and 116 nmol/L with dichloromethane extraction (n=10). Using tritiated cortisol, mean extraction efficiency for the ACS extraction protocol was 89% compared with 104% for the RIA method (n=6, P<0.001) and using urine spiked with ACS serum calibrator, extraction efficiency was only 76% (standard deviation 8.8%, n=49) on the ACS. Urine spiked with cortisol dissolved in ethanol also gave significantly lower recoveries on the ACS for both direct and extraction methods compared with the RIA. Regression analysis of results from a mixture of control serum samples and samples from patients (n=93) showed good correlations between the direct and extraction ACS methods and the RIA extraction assay. The median concentration in 23 normal subjects and 95% reference intervals (nmol/24 h) were: ACS direct, 237 (135-505); ACS extraction, 91 (33-239); and RIA extraction, 146 (80-334). 5Beta-dihydrocortisol was the only major interferent in all assays. The ACS extraction assay showed acceptable performance and correlated well with the extraction RIA, although there was evidence of matrix-dependent effects causing low recovery.

Case-Control Studies↗
PubMed1999

The objective measurement of remission and progression in metastatic breast cancer by use of serum tumour markers. European Group for Serum Tumour Markers in Breast Cancer.

An established biochemical index for monitoring therapy in patients with metastatic breast cancer was tested prospectively in a multicentre study. The index uses two serum tumour markers--carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) along with erythrocyte sedimentation rate (ESR). 67 patients treated by either endocrine or chemotherapy had CA15-3, CEA and ESR measured at diagnosis of metastases and sequentially during therapy. Two markers, CA15-3 and CEA, were measured on a further 16 patients giving a total of 83 patients who were assessable for CA15-3 and CEA. Of the patients with CA15-3, CEA and ESR measured at diagnosis of metastases 84% (56/67) had elevation of 1 or more markers. During therapy the number with elevated marker(s) rose to 96% (64/67). Changes in the markers were in line with and often pre-dated therapeutic outcome as assessed by the International Union Against Cancer (UICC) criteria both for remission and progression. Patients without elevation of markers on diagnosis subsequently showed a rise in the marker(s) at or before documented disease progression by UICC. The 3 women in whom markers were at no time significantly elevated remain in remission. The results using CA15-3 and CEA were similar but 12% less patients were assessable. CA15-3 and CEA (with and without ESR) provide an objective method to guide therapy in patients with metastatic breast cancer.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1999

Severe hypoglycaemia caused by raised insulin-like growth factor II in disseminated breast cancer.

A 60 year old woman with disseminated ductal carcinoma of the breast developed non-islet cell tumour induced hypoglycaemia (NICTH). The concentrations of the two insulin-like growth factors, IGF-I and IGF-II, were < 2 nmol/l and 94.1 nmol/l, respectively. The IGF-II to IGF-I ratio was > 47 (normal < 10). Insulin (< 3 mu/l) and C peptide (< 100 pmol/l) were both undetectable.

Adenocarcinoma, Papillary↗
PubMed1997

Spontaneous hypoglycaemia in a noninsulin-dependent diabetes mellitus patient with disseminated pancreatic carcinoma.

A 52-year-old-woman with non-insulin-dependent diabetes mellitus developed carcinoma of the pancreas and had a Whipple's resection performed. She required pancreatic exocrine supplements and insulin post-operatively. Five years later metastatic disease became apparent, and was accompanied by episodic spontaneous hypoglycaemia necessitating the cessation of insulin therapy. Hormonal analysis was performed, off insulin, at a time of hypoglycaemia (glucose 0.9 mmol l-1) and showed negligible insulin concentrations (< 2 mU l-1) but raised IGF-II together with low IGF-I concentrations (1.85 and 0.1 U ml-1, respectively). The association between diabetes and pancreatic carcinoma, and the pathogenesis of non-islet cell tumour induced hypoglycaemia (NICTH) are discussed.

Diabetes Mellitus, Type 2↗
PubMed1997

Pituitary dysfunction in recently post-menopausal women. Nottingham EPIC Study Group.

OBJECTIVE: Some recently post-menopausal women have lower than expected FSH concentrations, raising the possibility of subclinical hypothalamo-pituitary impairment. We have therefore performed pituitary stimulation tests in a group of recently post-menopausal women recruited to a bone loss prevention study. DESIGN: Prospective study of health volunteers. SETTING: Outpatient, teaching hospital in Nottingham UK. SUBJECTS: Forty-seven women selected from a cohort of 428 healthy volunteers to an osteoporosis prevention study all within 10 years of the menopause. MAIN OUTCOME MEASURES: Response of the pituitary to formal stimulation tests and its relationship to bone mineral density. RESULTS: A significantly attenuated response to pituitary stimulation was found in a group of otherwise healthy women with an FSH considered to be inappropriately low for the level of circulating oestradiol. The impaired responses were significant not only for FSH as expected but also to LH and prolactin at 1 hour after injection of GnRH and TRH (area under the curve, FSH P = 0.01, LH P = 0.001, prolactin P < 0.0001). TSH secretion was not significantly impaired. Baseline cortisol, growth hormone and thyroxine (T4) were normal in both control and test subjects. The test group was both heavier and taller, with a higher lean body mass, a higher body mass index and a greater total body fat than the controls. Bone mineral density showed no significant differences between the groups. Test subjects also had a higher free oestradiol index (P < 0.001) which correlated strongly (r = 0.534, P = 0.00026) with baseline FSH levels and possibly reflects a greater tissue exposure to biologically active hormone. Oestrone concentrations were, however, no different between the groups. CONCLUSIONS: Serum FSH concentrations are not invariably elevated in recently post-menopausal women and use of FSH as a determinant for postmenopausal status in clinical trials should be used with caution. Notwithstanding their higher free oestradiol index, women found to have an abnormally low basal FSH had evidence of poor prolactin, FSH and LH but not TSH responses to pituitary stimulation. This may represent either a degree of subclinical pituitary failure of a variant of normal. The low levels of gonadotrophin activity did not affect bone mineral density.

Bone Density↗
PubMed1997

Inhaled salmeterol or oral theophylline in nocturnal asthma?

Nocturnal cough and wheeze are common in asthma and often treated with beta2 agonists or theophyllines. As nocturnal asthma and these therapies may affect sleep and cognition, we compared 50 microg salmeterol inhaled every 12 h with individually dose-titrated sustained-release oral theophylline on sleep quality and cognitive performance in 15 patients with stable nocturnal asthma (overnight peak expiratory flow rate [PEFR] fall > or = 15%, > or = 1 asthmatic awakening/week) using a double-blind, double-dummy, crossover design with 14-d therapy limbs. Cognitive testing and polysomnography were performed on Nights 13 and 14. Trough plasma theophylline concentration after Night 14 on theophylline was median 11.1 (interquartile range 8.3, 15.2) microg/ml. Overnight PEFR falls were similar [salmeterol 2.3 (0, 10.6), theophylline 3.5 (-0.3, 9.6)%, p = 0.4] but on salmeterol there were more nights without awakenings [median difference 1 (0, 2), p < 0.01], fewer nocturnal arousals [difference -3 (-7, 2) h(-1), p < 0.05] and improved quality of life (p = 0.05). Sleep architecture did not otherwise differ. Visual vigilance improved on salmetrol (p < 0.05), but otherwise daytime cognition was unaffected. There was no patient preference for either therapy. Hence in patients with nocturnal asthma, we demonstrate no major clinical advantage, but a small benefit in sleep quality, quality of life, and daytime cognitive function with salmeterol.

Administration, Inhalation↗
PubMed1996

Salivary creatinine assays as a potential screen for renal disease.

Salivary creatinine concentrations are 10-15% of serum creatinine concentrations in healthy populations but have not previously been measured in patients with renal disease. The Cobas Mira automated Jaffé method was adapted to measure salivary creatinine concentration. The method was linear to 1200 mumol/L, had a mean recovery of 78% and a detection limit of 6 mumol/L. Intra-assay variability was 13.5, 5.5 and 1.4% at 10.6, 17.8 and 128.4 mumol/L, respectively. Inter-assay variability was 35.0 and 4.8% at 6.2 and 130.4 mumol/L, respectively. The median salivary creatinine concentrations was 8.5 mumol/L (range 6-18 mumol/L) in healthy subjects (n = 23), and 84 mumol/L (range 18-591 mumol/L) in patients with renal disease (n = 25). Salivary and serum creatinine concentrations were not related in healthy subjects, however, a significant relationship was found in the patients (r = 0.784, P < 0.001). Using salivary creatinine concentration of 16.8 mumol/L as a cut off value, all patients would have been detected with one false positive result (sensitivity 100%, specificity 95.7%, efficiency 97.7%). Thus, salivary creatinine estimations may be used to identify subjects with serum creatinine concentrations above 120 mumol/L.

Adult↗
PubMed1995

Set up and run an objective structured clinical exam.

Objective structured clinical exams are increasingly used as a way of assessing a range of clinical skills at both undergraduate and postgraduate level. To those planning to introduce such assessments, this article provides basic guidance on their development and structure and the personnel required. For those already using the assessments, our article may provide new ideas or be the impetus for an exchange of ideas. For those who are facing such formal assessment as candidates, we hope this article shows the efforts that are made to achieve the necessary structure and objectivity in this type of examination.

Clinical Competence↗
PubMed1995

Death in notified cases of tuberculosis in Edinburgh: 1983-1992.

Between 1983-1992, 730 cases of tuberculosis were notified in the Edinburgh area (population 6 x 10(5)). A review of available records identified 79 deaths (10.9% of all notifications). Thirty-seven patients (5.1%) died in the year following notification, 14 of these (five females, nine males; median age 71 years) due to tuberculosis. Five of these 14 deaths occurred within 7 days of starting chemotherapy and three deaths were due to miliary disease. Of 41 deaths (58%) before notification, 29 (19 females, 10 males; median age 77 years) were due to tuberculosis (autopsy rate 27/29) and 13 of these 29 deaths, all autopsied, were due to cryptic miliary disease. These findings reinforce continuing concerns about failure to diagnose tuberculosis, particularly cryptic miliary disease, in life.

Adult↗
PubMed1994

Effect of N-acetyl cysteine on the concentrations of thiols in plasma, bronchoalveolar lavage fluid, and lung tissue.

BACKGROUND: Oxidant/antioxidant imbalance may occur in the lungs of patients with chronic obstructive pulmonary disease (COPD). Glutathione is an important extracellular and intracellular thiol oxidant in the lungs. These studies were carried out to determine the effect of N-acetyl cysteine on thiol concentrations in plasma, bronchoalveolar lavage fluid, and lung tissue. METHODS: Studies were carried out on normal subjects, patients with COPD, and those undergoing lung resection. In the first study N-acetyl cysteine was given to three groups; healthy subjects (600 mg once daily by mouth) and two groups of patients with COPD. In the first group of patients with COPD the dose was 600 mg once daily and in the second 600 mg thrice daily, all for five days. The latter dosage regimen was also given to six patients before bronchoscopy and to 11 patients before lung resection. Lung glutathione (GSH) levels in bronchoalveolar lavage fluid or lung tissue were compared with the same numbers of patients who did not receive N-acetyl cysteine. RESULTS: N-acetyl cysteine was detected in plasma after a single 600 mg dose in normal subjects and patients with COPD up to 1.5 hours after the drug was given. Plasma cysteine concentrations increased in normal subjects on both days 1 and 5, and in patients with COPD on day 5. Glutathione concentrations in plasma increased on day 1 in normal subjects but not in patients with COPD given 600 mg N-acetyl cysteine daily. With the higher dose of 600 mg thrice daily, however, there was a sustained elevation of GSH concentrations in plasma in patients with COPD. In patients undergoing routine diagnostic bronchoscopy and bronchoalveolar lavage those who were given N-acetyl cysteine (600 mg) thrice daily for five days had higher concentrations of cysteine in the plasma, but no significant differences in cysteine concentrations in bronchoalveolar lavage or epithelial lining fluid compared with a control group; nor were there any differences in reduced glutathione concentrations in plasma, bronchoalveolar lavage or epithelial lining fluids between the control and treated groups. Moreover, in patients undergoing lung resection those treated with N-acetyl cysteine (600 mg thrice daily for five days) had similar concentrations of cysteine and glutathione in both plasma and lung tissue when compared with a control untreated group. CONCLUSIONS: These data suggest that, even when given in high oral doses, N-acetyl cysteine does not produce a sustained increase in glutathione levels sufficient to increase the antioxidant capacity of the lungs.

Acetylcysteine↗
PubMed1994

Neutrophil sequestration in lungs removed at surgery. The effect of microscopic emphysema.

Neutrophils within the lungs are considered to play an important role in the pathogenesis of pulmonary emphysema. We have studied the intravascular distribution of reinjected autologous 111In-labeled neutrophils in lung specimens resected 10 min after reinjection from 10 patients undergoing surgery for peripheral bronchogenic tumors. An excess of neutrophils relative to that expected for the 99mTc-labeled erythrocyte blood volume was confirmed in all specimens (range, 3- to 136-fold). In seven specimens which were completely examined, this excess displayed a skewed distribution, with a median neutrophil sequestration of 20-fold excess, and correlated with local blood volume (r = -0.51; p < 0.001). There was also a significant correlation between alveolar wall surface area per unit volume of lung (AWUV) and neutrophil excess, when randomly selected tissue blocks from each specimen were analyzed (r = 0.34, n = 51, p = 0.012). This same trend was demonstrated when whole specimen median values were considered (r = 0.64, n = 7, p = 0.07). Thus in areas of the lungs with lower AWUV values (increasing microscopic emphysema), fewer neutrophils were present. These studies add further support to the view that emphysema per se is not associated with an increased sequestration of pulmonary intravascular neutrophils.

Aged↗
PubMed1993

Epithelial mucin core antigen (EMCA) in assessing therapeutic response in advanced breast cancer--a comparison with CA15.3.

We report a comparative study of CA 15.3 and EMCA (epithelial mucin core antigen) in 77 consecutive women with newly diagnosed UICC assessable metastatic breast cancer, 59 patients received hormones and 18 chemotherapy. Assessments of response were made prior to commencing therapy and repeated 2 monthly. Sites of metastatic disease included bone (34), pulmonary (8), bone and pulmonary (14) and visceral (21). Using a cut-off of 33 U ml-1 changes in EMCA at 2, 4 and 6 months showed a highly significant correlation (P < 0.001) with UICC assessed response at 6 months; selectivity 70%, sensitivity 80%, specificity 91%, positive predictive value 84%; negative predictive value 89% at 2 months. Corresponding values for CA 15.3: selectivity 89%, sensitivity 85%, specificity 91%, PPV 92% and NPV 91%. Four of eight patients unassessable by CA 15.3 were assessable by EMCA; four patients expressed neither marker. EMCA appears to reflect tumour bulk and may be useful in monitoring therapy in patients with advanced breast cancer. With an easier and more robust assay format than CA 15.3, EMCA is potentially a more useful marker.

Adult↗
PubMed1993

Decreased leukocyte deformability after acute cigarette smoking in humans.

Acute cigarette smoking increases the sequestration of neutrophils in the lungs of humans. This may be due to the delayed transit of cells in the pulmonary microcirculation, which may result from a reduction in cell deformability as suggested by in vitro studies of smoke-exposed neutrophils. In order to support this hypothesis we wished to determine if a reduction in leukocyte deformability could be measured in whole blood exposed to smoke in vitro or in vivo. Whole blood filterability, which largely reflects leukocyte deformability, was measured as the pressure developed by filtration of diluted whole blood through a micropore membrane. Whole blood filtration pressures did not change when blood was exposed to smoke in vitro or in venous blood after acute smoking in vivo. However, arterial blood sampled from chronic smokers during acute smoking showed a consistent reduction in leukocyte deformability associated with a small increase in plasma elastase. To assess whether these changes were induced by oxidants in cigarette smoke, we measured the levels of the antioxidant glutathione (GSH), erythrocyte (RBC) membrane fragility, and products of lipid peroxidation in plasma and RBC in blood exposed to smoke in vivo and in vitro. No change in RBC lipid peroxidation or membrane fragility could be detected after in vitro smoke exposure, possibly because of the high antioxidant capacity of the RBC. However, reduced blood GSH levels and increased levels of lipid peroxidation products were detected in plasma, reflecting oxidant stress. In contrast, we were unable to detect evidence of an increased oxidant burden in blood after acute smoking in vivo, in either arterial or venous blood samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗