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Biomedical subjects

C T Brown

Publications and source records attributed to C T Brown.

At least 19 recordsLinked to original sources
PubMed2003

The fear of prostate cancer in men with lower urinary tract symptoms: should symptomatic men be screened?

OBJECTIVE: To explore the concerns and worries in men with uncomplicated lower urinary tract symptoms (LUTS, but no evidence of prostate cancer) relating to their symptoms. PATIENTS AND METHODS: There is no current prostate cancer screening programme in the UK. Evidence suggests that men with LUTS have the same risk of prostate cancer as aged-matched asymptomatic men. However, most men with LUTS are 'screened' with a digital rectal examination (DRE) and prostate specific antigen (PSA) testing as part of routine assessment. Whether this screening offers any benefit to patients and whether national screening for prostate cancer and subsequent early treatment offer any long-term survival or quality of life benefit is uncertain. Thus 30 men with uncomplicated LUTS were qualitatively interviewed to explore their concerns and worries about their symptoms. Interviews were transcribed verbatim and subjected to content analysis using validated techniques. RESULTS: Of the 30 men, 22 (73%) expressed a fear of prostate cancer at the time of their initial presentation. This fear was independent of race, social class and symptom severity; older men were less worried. Of the 22, 15 (68%) stated that after reassurance their symptoms were less bothersome and easier to cope with. CONCLUSIONS: These findings suggest there is a considerable gain in health by explicitly addressing the concerns of prostate cancer in men with uncomplicated LUTS. Informing these men of their true risk of prostate cancer (before or after a DRE and PSA estimate) may alleviate much of the bother associated with their symptoms. Despite no evidence of any greater risk of prostate cancer than in asymptomatic men, symptomatic men should continue to be screened after appropriate counselling.

Decision Making↗
PubMed2003

Lifestyle and behavioural interventions for men on watchful waiting with uncomplicated lower urinary tract symptoms: a national multidisciplinary survey.

OBJECTIVE: To determine the use of lifestyle and behavioural interventions in the UK for symptom control in men with uncomplicated lower urinary tract symptoms (LUTS) on watchful waiting (WW). METHOD: Semi-structured interviews with urologists, nurse practitioners and continence advisors were used to obtain a list of lifestyle and behavioural interventions used in men with LUTS. From the 18 interventions identified, a survey was constructed asking how often these interventions were used in routine practice. The survey was sent to 100 consultant urologists (British Association of Urological Surgeons), 100 nurse practitioners (British Association of Urological Nurses), and 100 continence advisors (International Continence Society) with an interest in male urology, all randomly selected. RESULTS: Of 248 (83%) responses, 236 were suitable for analysis; 193 (82%) of the respondents reported using lifestyle or behavioural interventions in men on WW with uncomplicated LUTS. The most frequently used interventions were education about the prostate and bladder, avoiding caffeine, urethral milking and reassuring men that they do not have prostate cancer. The use of lifestyle and behavioural interventions showed an 'all-or-none' pattern. Respondents used either few or many of the 18 interventions identified. There was considerable variation in the extent to which these interventions were used among the survey groups (P < 0.01); urologists used these interventions the least and continence advisors the most. CONCLUSIONS: Lifestyle and behavioural interventions are advised by many medical professionals to men on WW with uncomplicated LUTS. However, the use varies considerably, with some medical professionals advising many of these interventions and some a few or none at all. Further research is required to define and test the effectiveness of these interventions in reducing LUTS.

Aged↗
PubMed2002

Assessment, diagnosis and management of lower urinary tract symptoms in men.

Lower urinary tract symptoms are very common and the approach to assessment and management has changed dramatically over the past few years. Previously referred to as prostatism, benign prostatic hyperplasia and bladder outflow obstruction, it is now recognised that in most men symptoms are due to a combination of benign prostatic enlargement and age-related bladder dysfunction. Most men require only simple tests for a diagnosis, with the more complex investigations reserved for when the diagnosis is not clear. Symptom bothersomeness and effect on quality of life are the critical factors when deciding how to treat a man. A cascade of treatments exists, including conservative management, medical therapy and surgery. A man moves up the cascade when the present management strategy fails to control symptoms. Traditional surgical techniques such as transurethral resection of the prostate are still appropriate for some men, although with improved medical treatments available the number of men undergoing surgery is declining.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2001

Hydrogen-bond-mediated photoinduced electron-transfer: novel dimethylaniline-anthracene ensembles formed via Watson-Crick base-pairing.

The synthesis of a new, noncovalent anthracene-dimethylaniline dyad (ensemble I) held together via guanosine-cytidine Watson-Crick base-pairing interactions is reported. Upon excitation at 420 nm, photoinduced electron-transfer from the dimethylaniline donor to the singlet excited state of the anthracene acceptor occurs, as inferred from a combination of time-resolved fluorescence quenching and transient absorption measurements. In toluene at room temperature, the rate constants for photoinduced intraensemble electron-transfer and subsequent back-electron-transfer (charge recombination) are k(CS) = (3.5 +/- 0.03) x 10(10) s(-1) and k(CR) = (1.42 +/- 0.03) x 10(9) s(-1), respectively.

Aniline Compounds↗
PubMed1999

Characterization of proteoglycans synthesized by cultured corneal fibroblasts in response to transforming growth factor beta and fetal calf serum.

A culture system was developed to analyze the relationship between proteoglycans and growth factors during corneal injury. Specifically, the effects of transforming growth factor beta-1 (TGF-beta1) and fetal calf serum on proteoglycan synthesis in corneal fibroblasts were examined. Glycosaminoglycan synthesis and sulfation were determined using selective polysaccharidases. Proteoglycan core proteins were analyzed using gel electrophoresis and Western blotting. Cells cultured in 10% dialyzed fetal calf serum exhibited decreased synthesis of more highly sulfated chondroitin sulfate and heparan sulfate compared with cells cultured in 1% dialyzed fetal calf serum. The amount and sulfation of the glycosaminoglycans was not significantly influenced by TGF-beta1. The major proteoglycan species secreted into the media were decorin and perlecan. Decorin was glycanated with chondroitin sulfate. Perlecan was linked to either chondroitin sulfate, heparan sulfate, or both chondroitin sulfate and heparan sulfate. Decorin synthesis was reduced by either TGF-beta1 or serum. At early time points, both TGF-beta1 and serum induced substantial increases in perlecan bearing chondroitin sulfate and/or heparan sulfate chains. In contrast, after extended periods in culture, the amount of perlecan bearing heparan sulfate chains was unaffected by TGF-beta1 and decreased by serum. The levels of perlecan bearing chondroitin sulfate chains were elevated with TGF-beta1 treatment and were decreased with serum. Because both decorin and perlecan bind growth factors and are proposed to modulate their activity, changes in the expression of either of these proteoglycans could substantially affect the cellular response to injury.

Animals↗
PubMed1999

Visualizing evolutionary activity of genotypes.

We introduce a method for visualizing evolutionary activity of genotypes. Following a proposal of Bedau and Packard [11], we define a genotype's evolutionary activity in terms of the history of its concentration in the evolving population. To visualize this evolutionary activity we graph the distribution of evolutionary activity in the population of genotypes as a function of time. Adaptively significant genotypes trace a salient line or "wave" in these graphs. The quality of these waves indicates a variety of neutral variation, and random genetic drift. We apply this method in an evolutionary model of self-replicating assembly language programs competing for room in a two-dimensional space. Comparison with fitness graphs and with a nonadaptive analogue of this model shows how this method highlights adaptively significant events.

Biological Evolution↗
PubMed1995

Synthesis of stromal glycosaminoglycans in response to injury.

Our goal is to examine the synthesis and deposition of corneal glycosaminoglycans (GAGs) in response to a wound created by the insertion of porous discs into stromal interlamellar pockets. The disc and the surrounding stromal tissue were assayed and compared to contralateral control stroma and to sham operated corneas at 14, 42, and 84 days. The tissue and/or discs were removed and labeled with 35S-sulfate for 18 h; GAGs were extracted with 4 M guanidine-HCl. Extracts were chromatographed on Q-Sepharose columns, bound proteoglycans were eluted with a linear salt gradient, and radioactive fractions were analyzed. Total GAG content was determined colorimetrically, using dimethylmethylene blue. Specific GAGs were determined using enzymatic digestion with selective polysaccharide lyases and protein cores were examined using SDS-PAGE. The nonbound fractions from the chromatography were assayed for TGF-beta using Western blot analysis and for hyaluronic acid using an 125I-radiometric assay. Specific GAGs were localized 42 days after the disc had been implanted in the stroma. The placement of the discs into the stroma resulted in a decrease in the total amount of GAG. However, the ratio of dermatan-chondroitin sulfate and heparan sulfate to keratan sulfate increased in the surrounding tissue and disc. Hyaluronic acid was elevated at day 14 in the surrounding tissue, and not until day 84 in the disc. Western blot analysis of surrounding tissue extracts revealed forms of TGF-beta that migrated with an apparent molecular mass of 63 and 43 kDa. The results indicate that the insertion of discs into interlamellar pockets causes changes in the sulfation and proportion of the glycosaminoglycans in the surrounding tissue and the disc. These changes are coincident with the appearance of TGF-beta. After 84 days, the population of glycosaminoglycans in the disc begins to resemble the surrounding stroma. This model will allow us to examine further the synthesis and deposition of proteins following an extensive wound in which cells must migrate to the wound site and then undergo extensive remodeling.

Animals↗
PubMed1994

Age-related changes of scleral hydration and sulfated glycosaminoglycans.

Human scleras were analyzed to determine if tissue hydration changed in an age-related fashion, and whether this change could be related to decreased levels of glycosaminoglycans. The anterior half of normal human scleras were examined with donor ages ranging from newborn to 99 years (n = 40). Tissue hydration was found to decrease by 1.06% per decade (P = 0.0012). Glycosaminoglycans were extracted from scleras with guanidine hydrochloride, purified by anion exchange chromatography and quantitated using dimethylene blue and selective enzymatic digestion. The glycosaminoglycans of the sclera were primarily dermatan sulfate and chondroitin sulfate with small quantities of hyaluronic acid. While no loss of chondroitin sulfate with age was detected, a significant age-related loss of dermatan sulfate was found (P = 0.0006, n = 14). An examination of the relationship between glycosaminoglycan concentration and scleral hydration showed that increased levels of sulfated glycosaminoglycans were associated with increased levels of scleral hydration (P < 0.02, n = 14). No improvement in the correlation could be achieved by considering either dermatan sulfate or chondroitin sulfate individually. Our results suggest that, as in other connective tissues, aging is associated with a loss of glycosaminoglycans, and their loss is coincident with decreased tissue hydration.

Adolescent↗
PubMed1994

Evaluation of anti-CD5 ricin A chain immunoconjugate for prevention of acute graft-vs.-host disease after HLA-identical marrow transplantation.

Anti-CD5 ricin A chain immunoconjugate (XZ-CD5) is an immunotoxin that inhibits proliferative and cytotoxic responses to alloantigen in vitro and has activity in the treatment of acute graft-vs.-host disease (GVHD). To determine if XZ-CD5 could be used to prevent acute GVHD, 11 adult recipients of HLA-identical allogeneic marrow received XZ-CD5 0.1 mg kg-1 day-1 intravenously with high-dose methyl-prednisolone for 10, 14 or 17 doses early post-transplant. Six additional patients received 17 doses of XZ-CD5 and cyclosporine (CSA). All patients engrafted. Severe capillary leak syndrome was the most common serious toxicity and occurred more frequently in patients receiving CSA (5/5 vs. 3/11, P = 0.03). All evaluable patients developed acute GVHD; 88% had grade II-IV GVHD. Flow cytometric analysis demonstrated a substantial number of circulating CD5+ and CD3+ lymphocytes during and early after administration of XZ-CD5. These results suggest that the immunotoxin did not eliminate alloreactive T cells in this setting.

Acute Disease↗