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Biomedical subjects

R Davies

Publications and source records attributed to R Davies.

At least 91 records · Page 5Linked to original sources
PubMed1999

Immunocytochemical localization of oestrogen receptors in perichondrium of antlers in red deer (Cervus elaphus).

Remodelling of cancellous bone of antlers to compact bone can be stimulated by administration of oestrogens and previous work has demonstrated the presence of specific oestrogen binding in this tissue. In this study the presence of oestrogen receptors (ER) in antler tissue from red deer males was examined by immunocytochemistry using a monoclonal mouse anti-human ER serum. Strong positive staining was detected in the tip regions of immature antlers and was confined primarily to the cells forming a fibrous layer of the perichondrium. This finding indicates that the effects of oestrogens on remodelling of cancellous bone of the antler may be mediated indirectly by the surrounding connective tissue layers.

Animals↗
PubMed1999

Tamoxifen induces G:C-->T:A mutations in the cII gene in the liver of lambda/lacI transgenic rats but not at 5'-CpG-3' dinucleotide sequences as found in the lacI transgene.

Tamoxifen, a rat liver carcinogen, can induce mutations in the lacI gene in the livers of lambda/lacI transgenic rats. However, the presence of persistent tamoxifen adducts on the liver DNA raises the possibility that some contribution to the mutagenesis from ex vivo mutations during the in vitro lacI assay cannot be ruled out. To address this issue, mutagenesis at the cII gene of the transgenic shuttle vector was determined using a selection based assay which is unaffected by the presence of tamoxifen-DNA adducts. Female lambda/lacI transgenic rats were dosed orally with tamoxifen (20 mg/kg body wt) daily for 6 weeks, causing a 3.2-fold increase in the mutant frequency (MF) in the cII gene compared with that obtained with solvent treated animals. This was similar to the MF found previously at the lacI gene and confirms that tamoxifen is mutagenic in vivo. The major class of mutation induced by tamoxifen in the cII gene was G:C-->T:A transversions as was found previously in the lacI gene. However, in the one unreplicated study of mutations in the p53 gene of liver tumours induced by tamoxifen, no G:C-->T:A transversions were found; possible differences between mutagenesis in normal and tumour tissues are explored. The major proportion of the G:C-->T:A transversions occurred at 5'-CpG-3' dinucleotide (CpG) sites in the lacI gene, but not at such sites in the cII gene. The methylation of CpG sites greatly enhances the targeting of deoxyguanosine by carcinogens, thus this finding might be explained by differences in the methylation patterns at their respective CpG sites; however, nothing is known about the methylation status of either the lacI nor the cII gene in this transgenic rat. This study raises the important issue of which target genes (mammalian or transgenic) should be used as endpoints in mammalian mutagenesis assays.

Aflatoxin B1↗
PubMed1999

Extraction of teeth over 5 years in regularly attending adults.

OBJECTIVES: This prospective study was conducted to describe the incidence of tooth extraction in a group of regularly attending adults and to assess factors that are predictive of tooth loss. METHODS: Baseline and annual incremental clinical data were obtained from 23 general dental practitioners on a group of their regularly attending, dentate adult patients over a 5-year period. The patients completed a postal questionnaire with questions relating to dental health behaviours, attitudes and knowledge, and social factors. RESULTS: Complete clinical data were obtained from 2799 patients. Four hundred and seventy (17%) patients underwent extractions, 72% of which were posterior teeth. The majority of extractions were for reasons other than caries (79%). Bivariate analyses revealed many significant differences between patients who underwent extractions and those who did not, with respect to the clinical, social, behavioural and attitudinal variables. The logistic regression model for tooth loss included three clinical variables, number of teeth, crowns and sites with recession. Other variables in the final model included the dentist's and patient's prediction of treatment need, having sensitive teeth, having a sweet tooth, living alone and smoking. The sensitivity for the model was 0.57 with specificity 0.72. CONCLUSIONS: This study is unique in its examination of patients and has highlighted that both clinical and other factors are important in predicting who will undergo extractions. Future investigations should assess the consequence of having extractions in terms of health benefit or detriment.

Adult↗
PubMed1999

Asthma management with HFA-BDP (Qvar).

This report reviews the role of hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP; Qvar, 3M, Laughborough) in the management of asthma, based on pharmacokinetic, efficacy and safety clinical trial data presented at a satellite symposium to the European Respiratory Society in 1998. Qvar provides equivalent efficacy and safety to chlorofluorocarbon-BDP at about half the dose.

Anti-Asthmatic Agents↗
PubMed1999

Aortic dissection, patent ductus arteriosus, iris hypoplasia and brachytelephalangy in a male adolescent.

We describe a 14-year-old male with dissection of the descending aorta, bilateral iris hypoplasia, striae distensae and brachytelephalangy, the latter being most marked in the thumbs. Inguinal herniae and a patent ductus arteriosus were surgically repaired in infancy. The pattern of abnormalities may constitute a previously undescribed syndrome. The proband died suddenly at the age of 17 years.

Abnormalities, Multiple↗
PubMed1999

The Canadian Study of Cardiac Transplantation. Atherosclerosis. Investigators of the CASCADE Study.

OBJECTIVES: To describe risk factors associated with the development of transplantation coronary artery disease (TCAD). DESIGN: A retrospective study of the Canadian experience. PATIENTS: Seven hundred and nineteen patients with follow-up of at least 12 months following transplantation and a minimum of one coronary angiogram were analyzed. RESULTS: Two hundred and fourteen patients (30%) developed angiographic evidence of TCAD during an average follow-up of 50+/-25 months. Actuarial freedom rate from TCAD averaged 60%, and survival averaged 85% five years following transplantation. Abnormal coronary angiograms increased from 11% to 40% between the first and the fifth year following transplantation. The Cox multivariate final model showed that recipients of donor hearts of 50 years and older (RR 4.35, 95% CI 2.32 to 8.15), patients with two or more episodes of acute rejection (RR 1.56, 95% CI 1.11 to 2.21) and patients with a diagnosis of ischemic cardiomyopathy before transplantation (RR 1.38, 95% CI 1.03 to 1.84) were at higher risk of TCAD. The same risk factors also had a significant effect on survival, although patients who were administered a hepatic hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor during follow-up had a higher survival rate (95% versus 85%, P=0.01) five years following heart transplantation. CONCLUSIONS: Recipients of hearts from older donors, patients with an ischemic heart disease before transplantation and those with several episodes of acute rejection are at increased risk for TCAD. Patients who are administered an HMG-CoA reductase inhibitor during follow-up have a higher survival rate five years following transplantation.

Adult↗
PubMed1999

A six-week clinical efficacy study of a tooth whitening tartar control dentifrice for the removal of extrinsic tooth stain.

The objective of this double-blind clinical study was to investigate the tooth whitening efficacy of a new commercially available calculus-inhibiting dentifrice (Colgate Tartar Control Plus Whitening Fluoride dentifrice) containing tetra-sodium pyrophosphate, sodium tripolyphosphate, and PVM/MA copolymer in a 0.243% sodium fluoride/silica base (test dentifrice), compared to a commercially available, non-tooth whitening dentifrice containing 0.243% sodium fluoride in a silica base (control dentifrice). Following a baseline examination for, extrinsic tooth stain, qualifying adult male and female subjects from the Manchester, United Kingdom area were randomized into two treatment groups which were balanced for gender, age and level of extrinsic tooth stain. Subjects were instructed to brush their teeth twice daily (morning and evening) for one minute with their assigned dentifrice using a soft-bristled toothbrush. Examinations for extrinsic tooth stain were repeated after six weeks' use of the study dentifrices. Seventy-nine(79) subjects complied with the protocol and completed the entire study. At the six-week examination, subjects assigned to the test dentifrice treatment group exhibited statistically significant reductions of over 40% with respect to both extrinsic tooth stain area and extrinsic tooth stain intensity relative to those subjects assigned to the control dentifrice treatment group.

Adult↗
PubMed1998

Electropotential measurements as a new diagnostic modality for breast cancer.

BACKGROUND: Proliferative changes in breast epithelium are an intrinsic aspect in the development of breast cancer, and result in regions of epithelial electrical depolarisation within the breast parenchyma, which can extend to the skin surface. Diagnostic information might be obtained from a non-imaging and non-invasive test based on skin-surface electropotentials. METHODS: In 661 women, scheduled for open biopsy at eight European centres, we studied whether measurements of breast electrical activity with surface sensors could distinguish benign from malignant breast disease. A depolarisation index was developed. RESULTS: We found a highly significant trend of progressive electrical changes according to the proliferative characteristics of the biopsied tissue. Discriminatory information was obtained in both premenopausal and postmenopausal women, and the index was not related to age. The best test performances were for women with palpable lesions. The median index was 0.398 for non-proliferative benign lesions, 0.531 for proliferative benign lesions, and 0.644 for cancer (ductal carcinoma-in-situ and invasive). A specificity of 55% was obtained at 90% sensitivity for women with palpable lesions when a discriminant based on age and the depolarisation index was used. INTERPRETATION: This new modality may have diagnostic value, especially in reducing the number of unnecessary diagnostic tests among women with inconclusive findings on physical examination. Understanding and control of the biological variability of these electrical phenomena will be important in the improvement of this test. Studies in populations with a lower cancer prevalence are needed to assess further the diagnostic value of this approach.

Adolescent↗
PubMed1998

Safety of irbesartan in the treatment of mild to moderate systemic hypertension.

Nine multicenter, randomized, placebo-controlled studies were conducted to evaluate the safety and tolerability of the angiotensin II subtype 1 receptor blocker (AT1 blocker) irbesartan for the treatment of mild to moderate hypertension. After a 4- to 5-week placebo lead-in phase, patients were randomized to 4 to 12 weeks of double-blind therapy with either placebo (n = 641) or irbesartan (n = 1,965) at doses of 1 to 900 mg orally. All doses of irbesartan were well tolerated with no evidence of dose-related adverse effects. Across the full recommended clinical dose range, although not statistically significantly different, irbesartan use was associated with a lower incidence of adverse events, serious adverse events, and discontinuations due to adverse events compared with placebo. No clinically significant or unexpected changes in laboratory analyses were observed. Withdrawal of irbesartan therapy did not result in rebound hypertension or clinically important adverse events. Thus, irbesartan use in hypertensive patients was associated with a placebo-like safety and tolerability profile.

Adult↗
PubMed1998

Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.

Countless millions of people have died from tuberculosis, a chronic infectious disease caused by the tubercle bacillus. The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analysed in order to improve our understanding of the biology of this slow-growing pathogen and to help the conception of new prophylactic and therapeutic interventions. The genome comprises 4,411,529 base pairs, contains around 4,000 genes, and has a very high guanine + cytosine content that is reflected in the biased amino-acid content of the proteins. M. tuberculosis differs radically from other bacteria in that a very large portion of its coding capacity is devoted to the production of enzymes involved in lipogenesis and lipolysis, and to two new families of glycine-rich proteins with a repetitive structure that may represent a source of antigenic variation.

Chromosome Mapping↗
PubMed1998

Differential effects of mucosal pH on human (Caco-2) intestinal epithelial cell motility, proliferation, and differentiation.

Mucosal pH abnormalities are associated with anastomotic dehiscence, ischemia, and malignancy. We postulated that intraluminal pH influences intestinal epithelial motility, proliferation, and differentiation and studied extracellular pHo (7.0-8.5) effects on human (Caco-2) intestinal epithelial motility, proliferation, and differentiation. Mucosal healing was modeled by sheet migration and differentiation by alkaline phosphatase and dipeptidyl dipeptidase specific activity. In parallel differentiation and motility studies, we inhibited proliferation with mitomycin to dissociate indirect mitogenic effects. Intracellular pHi was quantitated using BCECF/AM at varying extracellular pHo and in migrating cells. Motility was maximal at pHo 7.6 and proliferation at 7.2. Each decreased with acidity and alkalinity. By contrast, brush border enzyme activity was lowest at pHo 7.0 and highest at pHo 8.5. pHi was highest at pHo 8.5. Migrating cell pHi was higher than static cell pHi. Thus, extracellular pHo deviations perturb Caco-2 pHi homeostasis and motility. Alkalinity promotes differentiation while acidity induces proliferation and limits differentiation.

Caco-2 Cells↗
PubMed1998

Evaluating screening policies for the early detection of retinopathy in patients with non-insulin dependent diabetes.

Retinopathy is a common complication of insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes, but serious visual loss may be prevented or delayed with sufficiently early diagnosis and treatment. Screening for early signs of retinopathy is clearly beneficial for some people, but there is no established consensus about who should be screened, by whom, by what technique and with what frequency, especially for NIDDM. The model described in this paper simulates the development of eye disease in a population of NIDDM patients and the effects of different screening schemes in terms of years of sight saved and the numbers of people prevented from suffering severe visual loss. The initial results indicate that blanket screening of all NIDDM patients may not be effective.

Adult↗
PubMed1998

Facial muscle spasms: an Australian study.

PURPOSE: A group of patients suffering from blepharospasm, hemifacial spasm and Meige's syndrome were surveyed to determine the delay from the onset of their condition until a correct diagnosis was reached, the attitudes of practitioners towards them and their condition, the effect of their condition on their lifestyle and the effects of different types of treatment on their conditions. METHODS: Questionnaires were offered to all patients with blepharospasm, hemifacial spasm and Meige's syndrome presenting to three ophthalmologists licensed to treat patients with botulinum toxin injections over a 12 month period. RESULTS: Patients consulted an average of 4.4 practitioners before a correct diagnosis was made and many waited a number of years before obtaining satisfactory treatment. Approximately two-thirds of all practitioners consulted were unaware of their condition. Ten per cent of patients reported a family history of similar conditions. Most patients received relief from their symptoms with treatment using injections of botulinum toxin. More than 55% of patients considered themselves to have psychological problems (usually relating to stress and trauma) that they associated with the onset of their condition. CONCLUSIONS: Facial muscle dystonias are rare and patient experiences suggest that they are poorly appreciated in the medical community. From the time they first see a practitioner with symptoms of facial dystonia, patients typically wait 2 years and see four practitioners before a correct diagnosis is made. Stress may be a factor in the symptomatic onset of this condition. Many patients describe pain as part of the presenting symptomatology. Botulinum toxin seems to be effective in the management of facial spasm.

Adult↗