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Biomedical subjects

W Farrell

Publications and source records attributed to W Farrell.

At least 19 recordsLinked to original sources
PubMed2000

The development of a semi-preparatory scale supercritical-fluid chromatograph for high-throughput purification of 'combi-chem' libraries.

A unique separator was developed which allowed automatic separation and peak collection using semi-preparative supercritical fluid chromatography (SFC). A peak detector switched the effluent between waste and special collection cassettes. Up to 50 mg of various solutes were injected onto a 21-mm I.D. Cyano column. The entire flow path was contained and no aerosols were generated. Collection efficiency was as high as 95%. Peak purity was often greater than 99. 9%. Typical run times were less than 10 min. An analytical SFC was used to screen the performance of a wide range of mobile and stationary phases for the elution of more than 60 miscellaneous small drug compounds. The best 'universal' gradient employed 0.4% isobutyl or isopropylamine dissolved in methanol, then mixed from 5 to 55% into carbon dioxide at 10%/min. Flow rate was 50 ml/min. The analytical SFC was shown to be a good predictor of the semi-prep instrumental performance.

4-Aminobenzoic Acid↗
PubMed2000

Hereditary non-polyposis colorectal cancer: an updated review.

INTRODUCTION: Colorectal cancer is the commonest cause of death due to malignancy in non-smokers in the western countries. The two main hereditary types of colorectal cancer are familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC), constituting approximately 10% of all cases of colorectal cancer. The main aim of this review is to reappraise the current advances in the genetics and diagnosis of HNPCC. METHODS: A Medline search was carried out to identify papers published from 1970 to 1999 on HNPCC. Embase and Cochrane databases were also searched. Reference lists of retrieved articles were carefully searched for additional articles. RESULTS AND CONCLUSIONS: Recent technological advances in the genetics of HNPCC have refined the criteria for diagnosis and management of HNPCC, however current policies regarding the testing of pedigrees are not clearly established. We believe that with the rapid development in this area definitive clinical guidelines will need to be available in future for the management of HNPCC.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1997

Tumour suppressor genes in the pathogenesis of human pituitary tumours.

Abnormal cell proliferation is controlled by opposing actions of oncogene products (stimulatory) and tumour suppressor gene (TSG) products (inhibitory). The former are dominantly acting, i.e. only one copy needed for tumorigenesis, whilst for TSG both copies of the gene must be inactivated so these are recessive at a cellular level. For anterior pituitary tumours only one oncogene (Gsp) has been identified in a variable proportion (4-40%) of a single tumour subtype (somatotrophinomas). Contrariwise, allelic deletion studies, using a PCR-based microsatellite polymorphism analysis of DNA extracted from archival specimens, have shown significant loss of heterozygosity in 20-40% of all tumour subtypes at the locus of the putative MEN-1 gene (chr. 11q13); the retinoblastoma gene (chr. 13q 12-14), and 10q26. Moreover, these DNA microdeletions were concentrated in radiologically invasive tumours compared to noninvasive tumours (modified Hardy gdes 3 and 4 vs. 1 + 2). In addition, 50% of Cushing's adenomas showed presence of p53 immunopositivity, though no point mutations in exons 4-9 were found, by SSCP analysis, to account for this. These studies show that analysis of TSGs in pituitary adenomas may provide clues to their pathogenesis, and more importantly relate to clinical behaviour of the tumour, and hence aid decisions regarding management.

Cell Division↗
PubMed1990

Defective glucocorticoid regulation of proopiomelanocortin gene expression and peptide secretion in a small cell lung cancer cell line.

A human small cell lung cancer cell line (COR L103) that actively expresses the proopiomelanocortin (POMC) gene has been used as a model of extrapituitary ACTH-secreting tumors to investigate the phenomenon of resistence of ACTH production to glucocorticoids. After both short term (24 h) and long term (10 days) exposure to hydrocortisone at concentrations of 500 and 1000 nM, the accumulation of intracellular POMC mRNA, ACTH, and ACTH precursor peptides in the culture medium was not suppressed. These finding contrast with those in the pituitary corticotroph cell line AtT20, in which POMC mRNA, ACTH, and ACTH precursors were suppressed under the same conditions. Two other genes that are regulated by glucocorticoids in other cell types, the tyrosine amino transferase gene and the glucocorticoid receptor gene, were expressed in COR L103 cells. However, neither gene appeared to be regulated by hydrocortisone in this small cell lung cancer cell line. Further studies demonstrated that glucocorticoid receptor binding could be detected in the nucleus and cytoplasm, with a Kd of 5 X 10(-9) M. It is concluded that nonsuppression of POMC by glucocorticoids is probably part of a more global defect of glucocorticoid signaling in these cells, but that this defect lies distal to steroid binding in the nucleus.

Adrenocorticotropic Hormone↗
PubMed1984

Administration and service delivery in the SSI program: the first 10 years.

This article provides an overview of the administrative structures and processes through which the Social Security Administration delivers its services to Supplemental Security Income (SSI) claimants and recipients. It documents the improvements and adjustments that have been made in the administration of SSI from 1974, when the program began, through 1983, the 10th year of its operation. The first decade of SSI was marked by significant changes that have led to improvements in fiscal responsibility and administrative efficiency for the program. Among the subjects covered are the legislative history of the program, the claims process, posteligibility procedures, underpayments and overpayments, the administrative complexities that have had to be surmounted, and administrative efforts aimed at quality assurance.

Aged↗
PubMed1976

Tobramycin, amikacin, sissomicin, and gentamicin resistant Gram-negative rods.

Sensitivities to gentamicin, sissomicin, tobramycin, and amikacin were compared in 196 gentamicin-resistant Gram-negative rods and in 212 similar organisms sensitive to gentamicin, mainly isolated from clinical specimens. Amikacin was the aminoglycoside most active against gentamicin-resistant organisms, Pseudomonas aeruginosa, klebsiella spp, Escherichia coli, Proteus spp, Providencia spp, and Citrobacter spp being particularly susceptible. Most of the gentamicin-resistant organisms were isolated from the urine of patients undergoing surgery. Gentamicin was the most active antibiotic against gentamicin-sensitive E coli, Proteus mirabilis, and Serratia spp. Pseudomonas aeruginosa and other Pseudomonas spp were most susceptible to tobramycin.

Amikacin↗
PubMed1976

The distribution of serotypes of Escherichia coli in cow-pats and other animal material compared with serotypes of E. coli isolated from human sources.

The serotypes of 13,139 strains of Escherichia coli isolated from humans were compared with the serotypes of 1076 strains isolated from animals. 689 of these strains were isolated from fresh cow-pats on 22 sites in England and Wales. 708 different O/H combinations were found. Of these, 520 were found in human strains only, 130 from animal strains only and 58 O/H serotypes from humans and animals. Approximately half of the animal strains could not be typed with the full set of sera used.

ABO Blood-Group System↗
PubMed1976

Comparison of urinary excretion of tobramycin and gentamicin in adults.

The urinary excretion of tobramycin and gentamicin was measured after intramuscular injections of 1 mg of each drug/kg in six normal volunteers. The antibiotics were assayed by the adenylyltransferase enzymatic method, which enables urine concentrations to be estimated accurately without dependence on urinary pH. The levels of the antibiotics in urine varied with the urine volume. The concentration of gentamicin was greater than 113 mug/ml and that of tobramycin was greater than 94 mug/ml 1 hr after administration. Urinary excretion of both antibiotics was rapid; 63.5% of the gentamicin and 74% of the tobramycin was excreted with 24 hr, with a large proportion being excreted by 4 hr after injection. There was a striking uniformity of individual values, and the method offers considerable advantages over existing microbiologic assays.

Adult↗