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Biomedical subjects

M Taylor

Publications and source records attributed to M Taylor.

At least 397 records · Page 22Linked to original sources

The synthesis of fluorine-18 lomefloxacin and its preliminary use in human studies.

Lomefloxacin is a new fluorine-containing antibiotic that has recently been approved for general use. Fluorine-18 lomefloxacin has been prepared by fluoride exchange between fluorine-18 fluoride and lomefloxacin in DMSO. Both time and temperature of the reaction have been optimized and conditions developed for the isolation and purification of the labeled product in a form suitable for oral administration. The exchange reaction provides sufficient labeled material for human studies with pharmacologically relevant quantities of the drug. We have performed preliminary human studies with this compound using positron emission tomography to estimate the tissue distribution of the compound and show the distribution of the compound into the liver and lungs.

Animals↗

Blood donor centres can effectively publicise cancer screening.

The ability of the blood transfusion service to promote cancer screening using the uptake of colorectal cancer screening offered to blood donors as a model was measured. Blood donors were sent an explanation of colorectal cancer screening with their appointment time to give blood. Free faecal occult blood tests (Haemoccult) were offered by a doctor to donors who attended the Leicester Blood Donor Centre. 556 registered blood donors (309 men, 247 women) aged 51 to 65 years were invited to donate blood over a three month period. Of the subjects who arrived to donate and accepted screening. 63% completed a faecal occult blood test with similar compliance in men and women (66% vs. 59%, chi 2 = 1.0, ns). Compliance was higher in older donors aged 61 to 65 years than those aged 51 to 60 years in both men (90% vs. 60%, chi 2 = 7.0, P < 0.01) and women (87% vs. 51%, chi 2 = 6.2, P < 0.02). The proportion of the total target population screened, which included those donors invited to give blood but who did not attend was 21%. This approach successfully targeted donors who attended to give blood, although only a small proportion of the total target population was screened. Blood donor centres could display cancer screening and health promotion literature and encourage doctors supervising sessions to provide further information and advice to donors.

Aged↗

Soft tissue growth of the oropharynx.

The purpose of this study was to describe the pattern of bony and soft tissue growth of the oropharynx in a sample of healthy, orthodontically untreated children. The sample consisted of 16 males and 16 females with lateral cephalograms at 6, 9, 12, 15, and 18 years of age, for a total of 160 lateral cephalometric radiographs. All subjects were enrolled in the Broadbent Bolton Study and their radiographs were used to produce the Bolton Standard Templates. Each radiograph was traced by hand and the tracings were paired and averaged to create a standard template for pharyngeal tissues at each age. In addition, all 160 tracings were digitized and means and standard deviations were calculated for 29 hard and 7 soft tissue measurements. Four linear (Ar-H,S-H,Go-H, Gn-H) and three angular (N-S-H, SN-ArH,GoGn-H) measurements demonstrated that the hyoid bone descends and moves slightly anteriorly up to age 18. The soft palate (PNS-P) increased 1 mm in length and 0.5 mm in thickness every 3 years after age 9. The distance between the anterior border of the atlas (ATA) and PNS did not change after age 12, while two soft tissue measurements (PNS-pharyngeal wall [PhW2] and posterior soft palate to pharyngeal wall [psp-PhW3]) increased. In general, two periods of accelerated change (6-9 years and 12-15 years) and two periods of quiescence (9-12 years and 15-18 years) were identified for the pharyngeal soft tissues. Further studies are needed to determine in soft tissues in the oropharynx continue to change after age 18.

Adolescent↗

The RpoN-box motif of the RNA polymerase sigma factor sigma N plays a role in promoter recognition.

The RNA polymerase sigma factor sigma N (sigma 54) is characterized by the presence, near the C-terminal end of the protein, of a highly conserved sequence of 10 amino acids (ARRTVAKYRE) that has been termed the RpoN box. In order to examine the function of this motif, which is predicted to adopt an alpha-helical structure, we have isolated a number of mutations that alter residues within the box and examined the properties of the sigma N derivatives encoded by them. Certain mutations that alter charged and potentially exposed residues within the motif result in transcriptionally inactive proteins with impaired promoter recognition but no impairment in core RNA polymerase binding. We therefore suggest that the RpoN box could play a direct or indirect role in recognition of the -24, -12 promoter consensus that is characteristic of sigma N-dependent genes.

Amino Acid Sequence↗

Molecular biology and evolution of resistance of toxicants.

To the prevailing biochemical/physiological classification of mechanisms of organismal resistance to toxicants, an additional molecular dimension is proposed. Predictions are developed regarding the relative prevalence of different classes of mutations and are found to compare favorably with reports from the literature. In particular, point mutations in target loci were the dominant form of resistance for both lab and field selection. Amplifications of target loci were less common than structural mutations, and more common for lab-selected than for field-selected strains. Amplification was the most common mechanism of up-regulation of metabolizing enzymes. In comparison, only one mutation involving cis-regulation and several involving trans-acting regulation were found. Mutations involving gene disruption and down-regulation were uncommon, but were found in appropriate cases, i.e., when toxicants stimulated rather than inhibited target function and when metabolizing enzymes converted toxicants into more toxic metabolites. Additional phenomena of likely but uncertain importance are genetic "succession," recombinational limitation, and negative cross-resistance. More work on these phenomena and on quantification of fitness costs of resistance is recommended.

Animal Population Groups↗

Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1.

Over 100 distinct disease-associated mutations have been identified in the breast-ovarian cancer susceptibility gene BRCA1. Loss of the wild-type allele in > 90% of tumors from patients with inherited BRCA1 mutations indicates tumor suppressive function. The low incidence of somatic mutations suggests that BRCA1 inactivation in sporadic tumors occurs by alternative mechanisms, such as interstitial chromosomal deletion or reduced transcription. To identify possible features of the BRCA1 genomic region that may contribute to chromosomal instability as well as potential transcriptional regulatory elements, a 117,143-bp DNA sequence encompassing BRCA1 was obtained by random sequencing of four cosmids identified from a human chromosome 17 specific library. The 24 exons of BRCA1 span an 81-kb region that has an unusually high density of Alu repetitive DNA (41.5%), but relatively low density (4.8%) of other repetitive sequences. BRCA1 intron lengths range in size from 403 bp to 9.2 kb and contain the intragenic microsatellite markers D17S1323, D17S1322, and D17S855, which localize to introns 12, 19, and 20, respectively. In addition to BRCA1, the contig contains two complete genes: Rho7, a member of the rho family of GTP binding proteins, and VAT1, an abundant membrane protein of cholinergic synaptic vesicles. Partial sequences of the 1A1-3B B-box protein pseudogene and IFP 35, an interferon induced leucine zipper protein, reside within the contig. An L21 ribosomal protein pseudogene is embedded in BRCA1 intron 13. The order of genes on the chromosome is: centromere-1FP 35-VAT1-Rho7-BRCA1-1A1-3B-telomere.

Breast Neoplasms↗

Peripheral blood leukocyte populations in the elderly with and without periodontal disease.

Periodontal disease in the elderly has not been characterized. Initial reports suggest that the disease is common and severe. Deficiencies in the immune response have also been reported to occur in the elderly. Consequently it was hypothesized that aging-related changes in the immune response may contribute to the severity and occurrence of periodontal disease in the elderly. To test that hypothesis, the % and number of leukocytes and leukocyte subsets in the peripheral blood of elderly (65-75 years) subjects were tested and used as indicators of the immune potential of those individuals. Age and gender effects on several of the parameters tested were identified. With the exception of increased number of leukocytes in the elderly group with severe periodontal disease, no other alteration in the leukocyte parameters tested were identified. These results suggest that periodontal disease in the elderly was not associated with obvious changes in the leukocyte and leukocyte subsets in the peripheral blood due to aging.

Adult↗

Missed cervical spine injury following barflying.

The case is reported of a young woman who suffered a wedge fracture of C7 due to axial loading with a flexed spine, in an injury caused by barfly jumping. The fracture was unstable and required surgical stabilisation. In this case the seriousness of the injury was not realised at first because neck radiographs were not taken at her initial assessment in accident and emergency.

Accidental Falls↗

Fifteen-year results of breast-conserving surgery and definitive breast irradiation for the treatment of ductal carcinoma in situ of the breast.

PURPOSE: To determine the 15-year outcome for women with ductal carcinoma in situ (DCIS, intraductal carcinoma) of the breast treated with breast-conserving surgery followed by definitive breast irradiation. PATIENTS AND METHODS: An analysis was performed of 270 intraductal breast carcinomas in 268 women from 10 institutions in Europe and the United States. In all patients, breast-conserving surgery included complete gross excision of the primary tumor followed by definitive breast irradiation. When performed, pathologic axillary lymph node staging was node-negative (n=86). The median follow-up time was 10.3 years (range, 0.9 to 26.8). RESULTS: The 15-year actuarial overall survival rate was 87%, and the 15-year actuarial cause-specific survival rate was 96%. The 15-year actuarial rate of freedom from distant metastases was 96%. There were 45 local recurrences in the treated breast, and the 15-year actuarial rate of local failure was 19%. The median time to local failure was 5.2 years (range, 1.4 to 16.8). A number of clinical and pathologic parameters were evaluated for correlation with local failure, and none were predictive for local failure (all P > or = .15). CONCLUSION: The results from the present study demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases following the treatment of DCIS of the breast using breast-conserving surgery and definitive breast irradiation. These results support the use of breast-conserving surgery and definitive breast irradiation for the treatment of DCIS of the breast.

Adult↗

Dysphagia lusoria: extrathoracic surgical management.

OBJECTIVE: To report a case of dysphagia lusoria managed by an extrathoracic approach. DESIGN: Case report and literature review. SETTING: A university hospital. PATIENT: A 39-year-old man, who presented with weight loss and dysphagia. Aortography and computed tomography revealed an aberrant subclavian artery compressing the esophagus against the aortic arch. INTERVENTION: The right subclavian artery was divided at its origin and reimplanted onto the right carotid artery. The operation was performed through a right supraclavicular incision without opening the chest. RESULTS: There was no operative morbidity. Six months postoperatively the patient was asymptomatic and had gained weight. There was no radiologic evidence of esophageal compression. CONCLUSIONS: Based on the results of our case of dysphagia lusoria and the reports of others that have started to appear in the literature, consideration should be given to repairing a symptomatic, nonaneurysmal aberrant right subclavian artery through an extrathoracic approach.

Adult↗

Inhibition of cysteine proteinases by Carica papaya cystatin produced in Escherichia coli.

A papaya cystatin (Cst)-encoding cDNA clone was isolated from a papaya leaf cDNA library and the active protein produced in Escherichia coli. The amino-acid sequence reveals a protein of 11,262 Da with over 40% identity to other published plant Cst. Unique features of the papaya Cst include a single Cys residue, variation in the papain-binding region, and the first reported inhibition of papaya proteinase IV by a Cst.

Base Sequence↗

Bleeding complications with the chimeric antibody to platelet glycoprotein IIb/IIIa integrin in patients undergoing percutaneous coronary intervention. EPIC Investigators.

BACKGROUND: The potential for novel antiplatelet and antithrombin agents to contribute to periprocedural bleeding complications of percutaneous coronary revascularization is poorly defined. In the Evaluation of c7E3 Fab in Preventing Ischemic Complications of High-Risk Angioplasty (EPIC) trial, the periprocedural use of aspirin, heparin, and a chimeric antibody to the platelet glycoprotein IIb/IIIa integrin c7E3 Fab in 2099 patients significantly reduced postprocedural ischemic complications and 6-month clinical restenosis but was associated with increased procedural bleeding complications. We review these complications and describe clinical and procedural variables associated with increased bleeding complications in the EPIC trial. METHODS AND RESULTS: Patients with high-risk clinical or lesion morphological characteristics were randomized to receive placebo bolus plus placebo infusion, c7E3 Fab bolus plus placebo infusion, or c7E3 Fab bolus plus c7E3 Fab infusion. Patients received periprocedural aspirin and intravenous heparin continued for a minimum of 12 hours after the procedure. Outcomes reflecting bleeding complications were measured: transfusions, decreased hemoglobin, and an index including both parameters. Major bleeding complications unrelated to bypass surgery occurred in 3.3%, 8.6%, and 10.6%, and blood product transfusions were used in 7.5%, 14.0%, and 16.8% of patients treated with placebo, bolus c7E3 Fab, and bolus plus infusion c7E3 Fab, respectively (both P < .001). Most major bleeding complications occurred at the femoral access site, regardless of treatment. Intracranial hemorrhage (0.3%) and death (0.09%) attributable to major bleeding complications were rare. Multivariable regression analyses identified several variables significantly and independently related to major bleeding complications or greater blood loss, including greater age, female sex, lower weight, c7E3 Fab therapy, and duration and complexity of the index procedure. Major bleeding complications and blood loss in patients receiving bolus plus infusion were not significantly greater than in those receiving bolus alone (P = .38 and P = .14, respectively). CONCLUSIONS: Bleeding complications unrelated to bypass surgery were two to three times more frequent in patients receiving c7E3 Fab than in those receiving placebo, but most were transient and well tolerated. Risk-factor analysis and modification of concomitant antithrombotic and antiplatelet treatment strategies may aid in reducing bleeding complications and enhancing clinical benefit in patients receiving c7E3 Fab during percutaneous coronary revascularization.

Aged↗

Didemnin B in favourable histology non-Hodgkin's lymphoma. A phase II study of the National Cancer Institute of Canada Clinical Trials Group.

Ten patients with previously untreated stage III/IV low grade histology non-Hodgkin's lymphoma received a 1-hour intravenous infusion of Didemnin B 2.3 mg/m2 weekly for 4 weeks repeated every 6 weeks. 40% of patients experienced significant hypersensitivity reactions, one of which was life-threatening, despite premedication with diphenhydramine and cimetidine. Other toxicities included nausea, vomiting, fatigue, diarrhea and skin rashes. No objective responses were seen. Given the serious toxicity and lack of activity in a non-pretreated group of patients, the study was closed early. Further investigation of Didemnin B at this dose and schedule is not recommended.

Antineoplastic Agents↗

Cancellous bone stresses surrounding the femoral component of a hip prosthesis: an elastic-plastic finite element analysis.

The cancellous bone stresses surrounding the femoral component of total hip replacement were investigated using the finite element method. Four versions of a certain femoral hip prosthesis (the Freeman, Corin Medical), cemented, HA coated, press-fit, and press-fit with ridges were analysed. Each model was subjected to two separate load cases with the cancellous bone modelled as an elastic perfectly plastic material. The effect of bone quality was investigated by varying the cancellous bone stiffness. The resulting cancellous bone stress distributions were compared to that of the intact femur. The results were also compared to clinical subsidence data (published elsewhere) for the Freeman femoral prosthesis to determine if the initial cancellous bone stress distribution could be used to predict the migration of the various versions of this prosthesis. The results showed that the press-fit designs of prosthesis generated substantially higher cancellous bone stresses than the cemented and HA coated designs, and that these stresses were up to 6.5 times higher than found in the intact femur. For all forms of fixation the cancellous bone stress distribution was found to be insensitive to changes in the trabecular bone stiffness: thus poor quality cancellous bone is more likely to promote 'plastic' deformation, and therefore subsidence of the prosthesis. Comparison with the clinical migration data showed a good correlation and revealed that it may be possible to use the calculated initial cancellous bone stresses to predict the migration of the implant, and hence the probability of early and mid-term aseptic loosening.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomechanical Phenomena↗

Decline in working memory associated with HIV infection. HNRC Group.

HIV infection has been associated with decline in a number of cognitive functions that are components of 'working memory'. Thus, tests of working memory that require the interaction of these components may be particularly sensitive to cognitive dysfunction that arises from HIV infection. To assess this possibility, working memory was examined in 147 HIV-seropositive (HIV+) and 38 HIV-seronegative (HIV-) males using the Reading Span Test and the Digit Span subtest from the Wechsler Memory Scale-Revised (WMS-R). Speed of information processing, a component of some working memory tasks, was assessed with a version of the Sternberg Memory Scanning task. Results indicated that symptomatic HIV+ subjects were impaired relative to HIV- control subjects on the Reading Span and Digit Span tests. Asymptomatic and mildly symptomatic HIV+ groups exhibited a trend toward impairment on these tests, and on the whole, a greater proportion of HIV+ subjects than HIV- subjects were impaired. The groups did not differ significantly in information processing speed. These results indicate that deficits in working memory are apparent in at least a subset of HIV-infected individuals. These deficits are most apparent in symptomatic HIV+ individuals, but the decline may begin during the asymptomatic phase of infection.

Adult↗