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Biomedical subjects

D McLeod

Publications and source records attributed to D McLeod.

At least 55 records · Page 3Linked to original sources
PubMed2001

A phase 3, multicenter, open-label, randomized study of abarelix versus leuprolide acetate in men with prostate cancer.

OBJECTIVES: To evaluate the levels of testosterone and other hormones in men with prostate cancer treated with abarelix versus leuprolide acetate. METHODS: Patients (n = 269) were randomized to receive open-label abarelix 100 mg or leuprolide acetate 7.5 mg by intramuscular injection. The results of the first 84 days of the study are reported. The primary efficacy endpoints included avoidance of testosterone surge, castration on day 8, and achievement and maintenance of castration from days 29 through 85. The secondary endpoints included castration on days 2, 4, and 15; a reduction in prostate-specific antigen level; and measurements of other hormones. Patients were monitored for clinical adverse events and laboratory abnormalities. RESULTS: No men in the abarelix group and 82% of men in the leuprolide acetate group experienced a testosterone surge (P <0.001). Abarelix caused rapid medical castration: 24% of men 1 day after treatment and 78% after 7 days compared with 0% of men treated with leuprolide acetate on either day. A comparable percentage of men achieved and maintained castration between days 29 and 85 in each group. Prostate-specific antigen had a statistically significant decrease for the first month in patients treated with abarelix. Dihydrotestosterone, luteinizing hormone, prostate-specific antigen, and follicle-stimulating hormone showed similar rapid reductions without an initial increase. The overall occurrence of adverse events was similar across the treatment groups, and most were sequelae of comorbid disorders. CONCLUSIONS: Treatment with abarelix produced a higher percentage of patients who avoided a testosterone surge and had a more rapid time to testosterone suppression with a higher rate of medical castration 1 day after treatment and greater reductions in testosterone, luteinizing hormone, follicle-stimulating hormone, and dihydrotestosterone during the first 2 weeks of treatment compared with leuprolide acetate. The achievement and maintenance of castration was comparable between the two groups.

Aged↗
PubMed2001

Collagen fibril organisation in mammalian vitreous by freeze etch/rotary shadowing electron microscopy.

Mammalian vitreous gel contains two major network-forming polymeric systems: long, thin fibrils comprising predominantly type II collagen and a meshwork of hyaluronan. The gel structure is maintained primarily by the collagen component, but little is known about the mechanisms of spacing of the collagen fibrils and of interactions between fibrils to form a stable network. In this study we have applied the technique of freeze etching/rotary shadowing electron microscopy in order to reveal the fibrillar network in central, cortical and basal vitreous and to understand the structural relationship between the collagen fibrils. The fibrils were arranged side by side in narrow bundles that frequently branched to link one bundle to another. Only a minor part of the fibrillar network consisted of segments that had a diameter of a single fibril (16.4nm mean diameter). In addition, three morphologically distinct filamentous structures were observed that appeared to form links within the collagen fibrillar network: short, single interlinking filaments of 7.0nm mean diameter, network-forming filaments of 6.7nm mean diameter, and longer filaments of 8.2nm mean diameter. All three types of filamentous structure were removed by digestion of the vitreous gels with Streptomyces hyaluronan lyase prior to freeze etching, indicating that these structures contain or are stabilised by hyaluronan. These filamentous structures may contribute to the structural stability of the vitreous gel.

Animals↗
PubMed2001

The bicalutamide Early Prostate Cancer Program. Demography.

BACKGROUND: The optimal treatment for early prostate cancer has yet to be established. A well-tolerated hormonal therapy such as bicalutamide could be a useful treatment option in this setting, either as adjuvant or immediate therapy. A major collaborative clinical trials program was set up to investigate bicalutamide as a treatment option for local prostate cancer (localized or locally advanced disease). METHODS: The bicalutamide Early Prostate Cancer program comprises three randomized, double-blind, placebo-controlled trials of similar design that are being conducted in distinct geographical areas (North America; Australia, Europe, Israel, South Africa and Mexico; and Scandinavia). Men with T1b-4N0-1M0 (TNM 1997) prostate cancer have been randomized on a 1:1 basis to receive bicalutamide 150 mg daily or placebo. Recruitment to the program closed in July 1998, and follow-up is ongoing. Study endpoints include time to clinical progression, overall survival and tolerability. RESULTS: 8113 men aged 38 to 93 years (mean 66.9) were randomized over a 3-year period. 67.4% of the enrolled patients had localized disease (T1-2) and 66.4% had a Gleason score </=6 at study entry, while the majority of patients had node-negative (N0) disease; only 3.1% in two of the studies and none in the third study had confirmed N+ disease. Overall, 71.8% of the patients received therapy of primary curative intent within 16 weeks of randomization; the remainder received watchful waiting as their primary approach. Across the program, the two randomized groups are well balanced. CONCLUSION: This is the largest randomized clinical trial program to date in local prostate cancer and is expected to provide critical information on the role of bicalutamide as an addition to standard care for patients with local prostate cancer who have received a therapy of curative intent or are candidates for watchful waiting.

Journal Article↗
PubMed2001

Randomised controlled trial of an integrated versus an optometric low vision rehabilitation service for patients with age-related macular degeneration: study design and methodology.

A number of studies have measured the outcomes of low vision care but these have usually been longitudinal case series, thus constituting very low quality of evidence for effectiveness. To date, there have been no randomised controlled trials (RCTs) which have evaluated the effectiveness and cost effectiveness of different models of care in low vision. The size of the low vision population and the paucity of systematic evaluation have created a pressing need for evidence about cost-effectiveness in order to inform service developments for low vision rehabilitation. This paper describes the study design and methodology of a three-arm RCT currently under way in Manchester. The baseline population recruited is also described. A traditional hospital-based optometric service is being compared with an integrated service (comprising the addition of community-based rehabilitation officer input) and with more generic community input (which is non-integrated and is not vision specific). A wide range of outcome measures are being assessed at recruitment and 12 months post-intervention, including low vision specific and generic quality of life measures, patterns of low vision aid use, and task performance. The rationale for the trial is discussed and the main study outcomes are described.

Aged↗
PubMed2000

Promotion of smoking cessation by New Zealand general practitioners: a description of current practice.

AIMS: To describe the advice and support New Zealand general practitioners (GPs) reported providing to patients about smoking cessation, to explore barriers encountered in providing this advice, and to compare reported practice with recommended best practice. METHODS: 450 GPs were surveyed from four different localities using a structured postal questionnaire. RESULTS: Questionnaires were returned by 283 GPs, giving a response rate of 63%. Approximately one-third of GPs asked every adult patient about their smoking status. Fewer recorded this information in the patient's notes. GPs, based on their own experience, considered nicotine replacement therapy (NRT) and their own advice to quit to be the two most useful smoking cessation strategies. They perceived patient resistance and time pressures as the main barriers limiting their ability to give advice to patients about smoking cessation. CONCLUSIONS: GPs provide smoking cessation advice to many patients, but this needs to be viewed in the context of the New Zealand fee-for-service primary care system and competing demands placed on the limited time available within a consultation. There is potential to increase the practice nurse's involvement in providing smoking cessation advice.

Adolescent↗
PubMed2000

Charged-particle multiplicity near midrapidity in central Au+Au collisions at sqrt[SNN]=56 and 130 GeV.

We present the first measurement of pseudorapidity densities of primary charged particles near midrapidity in Au+Au collisions at sqrt[s(NN)] = 56 and 130 GeV. For the most central collisions, we find the charged-particle pseudorapidity density to be dN/deta|(|eta|<1) = 408+/-12(stat)+/-30(syst) at 56 GeV and 555+/-12(stat)+/-35(syst) at 130 GeV, values that are higher than any previously observed in nuclear collisions. Compared to proton-antiproton collisions, our data show an increase in the pseudorapidity density per participant by more than 40% at the higher energy.

Journal Article↗
PubMed2000

Identification in vitreous and molecular cloning of opticin, a novel member of the family of leucine-rich repeat proteins of the extracellular matrix.

A prominent 45-kDa component was identified by protein staining following SDS-polyacrylamide gel electrophoresis of a 4 M guanidine hydrochloride extract from bovine vitreous collagen fibrils. Peptide sequences obtained from this component were used as a basis for the cloning (from human retinal cDNA) and sequencing of a novel member of the leucine-rich repeat extracellular matrix protein family that we have named opticin. Opticin mRNA was found by reverse transcription polymerase chain reaction in ligament and skin as well as in retina. An open reading frame containing 332 amino acids was identified, the first 19 amino acids representing a signal peptide. The deduced amino acid sequence of the mature protein encodes a 35-kDa protein with a calculated isoelectric point of 5.4. The central domain of this protein consists of six B-type leucine-rich repeats. This domain is flanked by cysteine clusters including a C-terminal two-cysteine cluster containing an additional leucine-rich repeat. The N-terminal region contains a cluster of potential O-glycosylation sites, and analysis of bovine vitreous opticin demonstrated the presence of sialylated O-linked oligosaccharides substituting the core protein. Opticin shows highest protein sequence identity to epiphycan (42%) and osteoglycin (35%) and belongs to Class III of the leucine-rich repeat extracellular matrix protein family.

Amino Acid Sequence↗
PubMed2000

Assessment of the diurnal variation in central corneal thickness and intraocular pressure for patients with suspected glaucoma.

OBJECTIVE: To assess whether a single daily measurement using ultrasonic pachymetry gives a representative assessment of mean central corneal thickness (CCT) in patients with suspected glaucoma and whether diurnal changes in CCT are related to diurnal variations in intraocular pressure (IOP). DESIGN: Cross-sectional study. METHOD: Central CCT and IOP were measured by a single observer in 56 eyes of 28 patients with suspected glaucoma using an ultrasonic pachymeter and a Goldmann tonometer. Four measurements were made over a 24-hour period: at 8:00 AM, 12:00 PM, 4:00 PM, and 8:00 PM. MAIN OUTCOME MEASURES: Intraocular pressure and pachymetry. RESULTS: Mean IOP was 19.80 mmHg at 8:00 AM (95% confidence interval [CI], 18.95-20.66 mmHg), 20.38 mmHg at 12:00 PM (95% CI, 19.49-21.26 mmHg), 19.91 mmHg at 4:00 PM (95% CI, 19.99-21.83 mmHg), and 19.23 mmHg at 8:00 PM (95% CI, 18.35-20.11 mmHg). Mean CCT was 569.4 microm (95% CI, 560.2-578.7 microm), 567.6 microm (95% CI, 558.4-576.7 microm), 569.1 microm (95% CI, 559.5-578.6 microm), and 567.2 microm (95% CI, 557.9-576.4 microm) at the four respective time points. There was no significant correlation between IOP and CCT in any patient (Pearson rank correlation coefficient); nor was there any significant correlation between the mean diurnal variations of IOP and CCT. CONCLUSIONS: In this group of patients with suspected glaucoma, there was no significant variation in CCT. Therefore, a single measurement of CCT is sufficient when assessing patients with suspected glaucoma. There was no correlation between change of IOP and change of CCT.

Aged↗
PubMed2000

Localization of pN-type IIA procollagen on adult bovine vitreous collagen fibrils.

Type II procollagen is synthesized in long (type IIA) and short (type IIB) forms because of alternative splicing of mRNA; the long form containing an additional cysteine-rich domain in the amino-propeptide. An antiserum (IIA) that recognizes this domain was used for immunolocalization studies on adult bovine vitreous at light and electron microscopic levels and for Western blot analyses. The immunolocalization studies revealed labelling by the IIA antiserum of the vitreous collagen fibrils. This labelling was removed by prior extraction of the fibrils with 6 M guanidine hydrochloride (GuHCl) and the extract was shown to contain pN-type IIA procollagen. Adult vitreous collagen fibrils are coated with pN-type IIA procollagen, a finding with potential implications for vitreous collagen fibril structure and function.

Animals↗
PubMed2000

Vitrectomy for vitreous opacification in Fuchs' heterochromic uveitis.

PURPOSE: To assess the role of pars plana vitrectomy (PPV) for symptomatic vitreous opacification in a series of patients with Fuchs' heterochromic uveitis (FHU). METHODS: A retrospective review was undertaken of 13 patients with FHU who underwent vitrectomy for vitreous opacification between April 1989 and December 1998. RESULTS: An improvement in visual symptoms was recorded in all patients, 9 of 13 (69%) demonstrating at least a 2 line increase in Snellen visual acuity. All but one patient attained 6/9 or better visual acuity post-operatively. Surgery was uneventful and did not appear to exacerbate any existing intraocular inflammation. CONCLUSION: From this series we conclude that PPV has an important role in the management of patients with FHU who present with symptomatic vitreous opacification.

Adult↗
PubMed2000

IL-10 and antibodies to TGF-beta2 and PDGF inhibit RPE-mediated retinal contraction.

PURPOSE: Retinal pigment epithelial (RPE) cells are believed to play a pivotal role in the formation and contraction of epiretinal membranes in proliferative vitreoretinopathy (PVR). In the present study, an organ culture method was used that mimics the contractile stage of PVR, to investigate the contribution of a variety of growth factors in human RPE cell-mediated contraction of the retina. METHODS: Cultured human RPE cells were seeded onto bovine retinal explants. After attachment, cultures received one of the following exogenous growth factors: platelet-derived growth factor (PDGF)-AB, PDGF-BB, basic fibroblast growth factor (bFGF), transforming growth factor (TGF)-beta1, TGF-beta2, or interleukin (IL)-10; or a neutralizing antibody to PDGF and/or TGF-beta2. Control explants were either untreated or received a null antibody. Contraction was assessed by image analysis and expressed as percentage reduction in retinal area. RESULTS: RPE cells produced a more than 50% contraction of the retina after 7 days in untreated samples. PDGF and TGF-beta2 stimulated RPE-mediated contraction by a further 20% at 100 ng/ml. IL-10 decreased contraction by 63%, whereas the other growth factors gave rise to similar contraction to untreated controls. Neutralizing antibodies against PDGF and TGF-beta2 reduced RPE-mediated contraction by up to 70% in comparison with untreated controls. The neutralizing antibodies also inhibited the effects of exogenous PDGF and TGF-beta2 on RPE-mediated contraction of the retina (P < 0.01). CONCLUSIONS: These findings confirm a role for both PDGF and TGF-beta2 in RPE cell-mediated contraction of the retina. Such contraction can be inhibited by neutralizing antibodies against PDGF and TGF-beta2, which, together with IL-10, are putative candidates for therapeutic intervention in PVR.

Animals↗
PubMed1999

Influence of age on the parasympatholytic property of tricyclic antidepressants.

Clinical evidence indicates that parasympatholytic effects of tricyclic antidepressants increase with age. The aim of the present study was to determine the possible physiological reason for this phenomenon. Subjects included 23 patients (14 female) with major depression, melancholic type, and 23 age- and sex-matched healthy control subjects. Cardiac vagal tone was measured at rest using both spectral analysis and a time domain beat-to-beat method. Results of the spectral and time domain methods for the estimation of vagal tone used in this study were highly correlated in control subjects as well as in medicated depressed subjects. Both patients and control subjects showed an age-related decline in cardiac vagal tone. Tricyclic antidepressants decreased vagal tone significantly by 25-49% depending on age (20-60 years), although the age difference was not significant. The greater effect of tricyclic antidepressants on parasympathetic activity typically seen in older age groups may reflect the fact that predrug levels of vagal tone are already low in older patients. Measurement of vagal tone prior to drug administration may therefore be of prognostic value for anticholinergic side effects.

Adult↗