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Biomedical subjects

P Day

Publications and source records attributed to P Day.

At least 37 records · Page 2Linked to original sources
PubMed1997

Biochemical, histomorphometric and densitometric changes in patients with multiple myeloma: effects of glucocorticoid therapy and disease activity.

It is unknown whether bone changes which can occur in multiple myeloma (MM) are due to cytokine-induced osteoclastic bone resorption from a clone of abnormal plasma cells or high-dose glucocorticoid therapy. We studied 25 MM patients treated for 1-12 years with combination chemotherapy, subdivided into two groups. Group 1 consisted of 12 patients with stage I and II myeloma and group 2 consisted of 13 patients with stage III MM. Their serum biochemistry, tetracycline-labelled bone histomorphometry and bone densitometry were compared to age- and sex-matched controls. Patients with MM demonstrated increased indices of bone resorption (P < 0.001 versus controls) and, to a lesser extent, increased indices of bone formation (P < 0.01 versus controls). No patient had evidence of a mineralization defect. Lumbar spine, femoral neck and total body bone mineral density measurements (BMD) were significantly lower in group 2 compared with group 1 (P < 0.05). Following 12 months of therapy, lumbar spine BMD decreased by 6.6% (95% CI, 2.7% to -9.3%) and femoral neck BMD decreased by 9.5% (95% CI, -3.2% to -15.9%). In a stepwise regression analysis, cumulative prednisolone dosage (B Coef. = -0.39; P = 0.03) and plasma cell infiltrate (B Coef. = -0.08; P = 0.05) were the most important predictors of lumbar spine bone loss, whereas serum paraprotein (B Coef.= -0.35; P = 0.02) and plasma cell infiltrate (B Coef. = -0.20; P = 0.04) were the most important predictors of femoral neck bone loss. We conclude that MM is characterized by high bone turnover with osteoblast-osteoclast uncoupling. Both disease activity and high-dose glucocorticoid therapy may be responsible for the ongoing bone loss seen with MM.

Absorptiometry, Photon↗
PubMed1996

Fine adjustments in thyroxine replacement and its effect on bone metabolism.

We studied 10 postmenopausal women with Hashimoto's hypothyroidism treated with varying doses of L-thyroxine replacement. Each patient received incremental doses of L-thyroxine sufficient to achieve subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism as determined by normal total serum thyroxine levels (80-160 micrograms/L) and serum TSH concentrations greater than 3.5, 0.3-3.5, and less than 0.3 mU/L, respectively. Metabolic parameters of bone turnover (including serum bone Gla-protein, serum alkaline phosphatase, serum procollagen 1, and serum carboxytelopeptide) were assessed once steady state was achieved, and measurements were compared to 10 healthy controls matched for age and years since the menopause. Our findings suggest that overzealous thyroxine replacement producing subclinical hyperthyroidism may result in an increase in bone turnover as reflected by elevated serum carboxytelopeptide concentrations.

Adult↗
PubMed1996

A new method for measuring menstrual blood loss and its use in screening women before endometrial ablation.

OBJECTIVE: 1. To develop and validate a method for measuring menstrual blood loss in a routine setting, and 2. To assess the value of measuring menstrual blood loss before endometrial ablation. DESIGN: A prospective, observational study. SETTING: Four Yorkshire hospitals: The General Infirmary at Leeds, St. James's University Hospital, Leeds, St. Luke's Hospital, Bradford and The Friarage Hospital, Northallerton. PARTICIPANTS: Three hundred and seventy-two women who had been offered endometrial ablation for menorrhagia. MEASUREMENT: Sanitary material was washed with a nonionic detergent in a known volume of water. The haemoglobin in a sample of solution was measured by mixing with sodium carbonate for spectrophotometric analysis. INTERVENTIONS: The menstrual blood loss result was revealed to each women. Electrosurgical endometrial ablation was performed for those who decided to have surgery. MAIN OUTCOME MEASURES: Proportion of women with normal menstrual blood loss (< or = 80 mL) who avoided surgery. Comparison of endometrial ablation outcome in women with and without genuine menorrhagia. RESULTS: Thirty-six women (10%) with normal menstrual blood loss who declined surgery continued to avoid surgery after a mean of 27 months. Two hundred and ninety-two women were followed up for one year after endometrial ablation. Those with genuine menorrhagia (n = 122) were less likely to be dissatisfied (9% vs 18%) (OR 2.5, 95% CI 1.1-4.7) or to require hysterectomy (4% vs 7%) (OR 1.8, 95% CI 0.6-5.2) than women with normal menstrual blood loss (n = 170). CONCLUSIONS: The objective diagnosis of menorrhagia can be undertaken in a routine setting and may provide some women, who have a normal menstrual blood loss, sufficient reassurance to refrain from surgery. Women with genuine menorrhagia have a better outcome after endometrial ablation than those with normal menstrual blood loss.

Adult↗
PubMed1995

Changes in cancer incidence and mortality in New South Wales.

OBJECTIVE: To assess changes in cancer incidence and mortality in New South Wales (NSW) between 1973-1977 and 1988-1992. DESIGN: Descriptive analysis of statutory cancer notifications to the NSW Central Cancer Registry. OUTCOME MEASURES: Age-standardised incidence and mortality rates calculated with the "world" standard population. RESULTS: Overall cancer incidence rose markedly, from 251 to 318 per 100,000 in men and from 202 to 241 per 100,000 in women. The rise was greatest in the 60-and-over age group. Cancer mortality fell marginally in men (from 166 to 162 per 100,000) and did not change in women (100 per 100,000 in both periods). It fell in the under-60 age group, and remained stable or rose in older people. Prostate and breast cancers and melanoma of the skin accounted for about half the increase in incidence. Both incidence and mortality increased significantly (P < 0.01) for melanoma and non-Hodgkin's lymphomas in men and lung cancer in women, and fell substantially for stomach cancer in both sexes, lung cancer in men and cervical cancer in women. Despite increasing incidence, mortality, also fell for testicular cancer in men and rectal cancer in women and for leukaemias in children. CONCLUSIONS: The major factor causing the increased incidence of overall cancer was earlier detection. Altered exposure to risk factors could be identified for only a minority of the changes.

Adolescent↗
PubMed1995

Rationing in the NHS: the dance of the seven veils-in reverse.

The 1991 reforms of the National Health Service set up the expectation that rationing would in future be explicit instead of, as in the past, implicit. This has not happened. Research carried out at the University of Bath shows that very few health authorities are rationing by exclusion on the Oregon model. Instead, both central Government and health authorities are continuing to diffuse responsibility among the medical profession. This paper analyses the reasons why. Rationing by delay and dilution are more significant-as well as less visible-than rationing by exclusion. And it is the medical profession which controls the flow of patients through waiting lists and the way in which resources are used during treatment. Similarly, it is in the self-interest of both central Government and health authorities that their resource decisions should continue to be disguised behind the veils of clinical discretion. Despite pressures for greater transparency, Britain's opaque form of rationing may therefore survive.

Forecasting↗
PubMed1995

Cytokine mRNA expression in the mucosa of treated coeliac patients after wheat peptide challenge.

This study investigated the presence of mRNA coding for interferon gamma (IFN gamma), tumour necrosis factor alpha (TNF alpha), and interleukins 2 (IL2) and 6 (IL6), in the mucosa of four coeliac patients in remission who had been challenged with either gliadin or synthetic gliadin oligopeptides. Jejunal biopsy specimens from these patients, taken before and at two, four, and six hours after challenge, were hybridised with specific 35S-labelled DNA oligonucleotide probes. The lamina propria of all the patients contained significantly increased numbers of cytokine mRNA expressing cells four hours after challenge with gliadin or an oligopeptide corresponding to amino acids 31-49 of A-gliadin (peptide A). No significant changes were seen with the peptides corresponding to aminoacids 202-220 (peptide B) or 3-21 (peptide C) of A-gliadin, with the exception of one patient who showed a significant increase in the number of TNF alpha mRNA expressing cells four hours after challenge with peptide B. In vivo studies in coeliac disease have shown that significant histological changes occur in the mucosa of treated coeliac patients four hours after challenge with either gliadin or peptide A. These findings suggest that the histological changes seen previously in the mucosa of coeliac patients after wheat peptide challenge may be caused by increased expression of cytokines within the mucosa.

Adult↗
PubMed1995

In vitro toxicity of gluten peptides in coeliac disease assessed by organ culture.

BACKGROUND: We have used organ culture to investigate the in vitro toxicity of three oligopeptides corresponding to amino acids 31-49 (peptide A), 202-220 (peptide B), and 3-21 (peptide C) of A-gliadin, Frazer's fraction III (FFIII), and ovalbumin. METHODS: Eight to 14 jejunal biopsy specimens were obtained from each of 8 treated and 7 untreated coeliac patients and 5 normal controls and cultured for 18 h in organ culture with test peptide (1 mg/ml) or medium alone. Mean enterocyte cell heights (ECH) were compared with paired values for specimens grown in medium alone. RESULTS: A significant reduction in the mean of the ECH values for each of the patient groups was observed with peptide A and FFIII in both treated (p = 0.01 and 0.02, respectively) and untreated (p = 0.03 and 0.01) coeliac patients when compared with tissue incubated with medium alone. No significant changes in the mean ECH value were noted in any of the patient groups in tissue incubated with peptide B, peptide C, or ovalbumin as compared with those with medium alone. CONCLUSIONS: These results suggest that peptide A is toxic in vitro to the jejunal mucosa of both treated and untreated coeliac patients, correlating with recent findings that this peptide exacerbates coeliac disease in vivo.

Adult↗
PubMed1995

Temporal integration differences between crossed and uncrossed stereoscopic mechanisms.

In this study, we investigated temporal integration of disparity information for crossed and uncrossed stereopsis. Across three experiments, exposure duration thresholds were measured for stereoscopic stimuli created from dynamic random-dot stereograms. In Experiment 1, an investigation of disparity detection showed that detection thresholds were equal for the crossed and uncrossed directions. In Experiment 2, an examination of duration limits for depth perception showed that critical durations were lower, and depth more veridical, for crossed depth than for uncrossed depth. In Experiment 3, an investigation of depth discrimination revealed that discrimination thresholds were lower for crossed depth than for uncrossed depth. These results suggest that crossed and uncrossed mechanisms differ in terms of their temporal integration properties at processing levels involving the computation and discrimination of depth.

Depth Perception↗
PubMed1994

Wheat peptide challenge in coeliac disease.

The exact nature of the cereal moiety that exacerbates coeliac disease is unknown. In-vitro studies have implicated both the N-terminal and far C-terminal domains of one of the wheat prolamins, A-gliadin. Peptides within these regions may act as epitopes that trigger immune events leading to enteropathy. We synthesized three peptides corresponding to amino-acids 3-21, 31-49, and 202-220 of A-gliadin. Four patients with coeliac disease were challenged by intraduodenal infusion of 1 g of gliadin or 200 mg of the synthetic peptides. Jejunal biopsies were taken before and at hourly intervals for 6 h after the infusion. Morphometric variables were measured and intraepithelial lymphocytes counted. Significant histological changes occurred in the small intestinal mucosa after challenge with a synthetic peptide corresponding to amino acids 31-49 of A-gliadin. The N-terminal peptide, residues 3-21 of A-gliadin, did not cause histological changes in any of the patients. In one of the four patients, minor histological changes following challenge with the peptide corresponding to residues 202-220 of A-gliadin were seen. Our results suggest that the oligopeptide corresponding to aminoacids 31-49 of A-gliadin is toxic in vivo, but there is no evidence of toxicity of the far N-terminal peptide, residues 3-21. The C-terminal peptide 202-220 may contain an epitope to which patients with coeliac disease display variable sensitivity. Since the oligopeptide corresponding to amino-acids 31-49 of A-gliadin is recognised by HLA DQ2-restricted T cells, the observed effects may be due to immune activation within the intestinal mucosa.

Adult↗
PubMed1994

Measurement of gluten using a monoclonal antibody to a sequenced peptide of alpha-gliadin from the coeliac-activating domain I.

A monoclonal antibody, raised against a sequenced 54 amino-acid peptide from the coeliac-activating N-terminal region of alpha-gliadin, was used in an assay for the measurement of gluten in foods. A double-sandwich ELISA using a polyclonal capture antibody produced standard curves for unfractionated gliadin and its alpha, beta, gamma and omega subfractions, and for rye, barley and oat prolamins. The sensitivity of the assay for unfractionated gliadin and rye prolamins was 15 ng/ml, for barley and oat prolamins 125 and 250 ng/ml, respectively. Prolamins from coeliac non-toxic rice, maize, millet and sorghum did not cross-react in the assay.

Antibodies, Monoclonal↗