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Biomedical subjects

D McLeod

Publications and source records attributed to D McLeod.

At least 37 records · Page 2Linked to original sources
PubMed2003

Immediate treatment with bicalutamide 150mg as adjuvant therapy significantly reduces the risk of PSA progression in early prostate cancer.

OBJECTIVE: To evaluate the effect of bicalutamide ('Casodex') 150mg (in addition to standard care), on the risk of prostate-specific antigen (PSA) progression, in patients with early prostate cancer. METHODS: The bicalutamide 150mg Early Prostate Cancer (EPC) programme is the largest clinical trial programme in the treatment of prostate cancer to date. This paper reports the PSA progression data from the EPC programme at a median of 3years' follow-up, for the overall study population, and across the radical prostatectomy and radiotherapy primary therapy strategies. PSA progression was predefined as the earliest occurrence of PSA doubling from baseline, objective progression, or death from any cause. RESULT: Overall, bicalutamide 150 mg in addition to standard care significantly reduced the risk of PSA progression by 59% compared with standard care alone (HR 0.41; 95% CI 0.38, 0.45; p<<0.0001). Significant reductions were observed following radical prostatectomy (51%; HR 0.49; 95% CI 0.43, 0.56; p<<0.0001) and radiotherapy (58%; HR 0.42; 95% CI 0.33, 0.53; p<<0.0001). Further exploration of the data by disease stage, nodal status, Gleason score and pre-treatment PSA level revealed significant reductions in the risk of PSA progression across most prognostic risk factor subgroups. CONCLUSIONS: Bicalutamide 150mg significantly reduces the risk of PSA progression, irrespective of whether patients received radical prostatectomy or radiotherapy as standard care. The EPC programme is ongoing and further progression and survival data are awaited.

Adult↗
PubMed2003

Correlation of a scanning laser derived oedema index and visual function following grid laser treatment for diabetic macular oedema.

AIM: To correlate change of an oedema index derived by scanning laser tomography with change of visual function in patients undergoing grid laser photocoagulation for clinically significant diabetic macular oedema (DMO). METHODS: The sample comprised 24 diabetic patients with retinal thickening within 500 micro m of the fovea. Inclusion criteria included a logMAR visual acuity of 0.25, or better. Patients were assessed twice before a single session of grid laser treatment and within 1 week of, and at 1, 2, 4, and 12 weeks after, treatment. At each visit, patients underwent logMAR visual acuity, conventional and short wavelength automated perimetry (SWAP), and scanning laser tomography. Each visual function parameter was correlated with the mean oedema index. The mean oedema index represented the z-profile signal width divided by the maximum reflectance intensity (arbitrary units). A Pearson correlation coefficient (Bonferroni corrected) was undertaken on the data set of each patient. RESULTS: 13 patients exhibited significant correlation of the mean oedema index and at least one measure of visual function for the 10 degrees x 10 degrees scan field while 10 patients correlated for the 20 degrees x 20 degrees scan field. Seven patients demonstrated correlation for both scan fields. Laser photocoagulation typically resulted in an immediate loss of perimetric sensitivity whereas the oedema index changed over a period of weeks. Localised oedema did not impact upon visual acuity or letter contrast sensitivity when situated extrafoveally. CONCLUSIONS: Correlation of change of the oedema index and of visual function following grid laser photocoagulation was not found in all patients. An absence of correlation can be explained by the localised distribution of DMO in this sample of patients, as well as by differences in the time course of change of the oedema index and visual function. The study has objectively documented change in the magnitude and distribution of DMO following grid laser treatment and has established the relation of this change to the change in visual function.

Aged↗
PubMed2003

Analysis of bronchovascular downstream blood pressure changes in exercising sheep.

The relative roles of neural and pressure gradient factors, causing a fall or maintenance of bronchial blood flow in exercising sheep, are unknown. These were examined in sheep prepared under thiopentone/isoflurane general anaesthesia with a pulsed Doppler probe mounted on the bronchial artery, and aortic pressure (Pa) catheter in superficial cervical artery. After recovery, Swan-Ganz catheters were inserted under local anaesthesia into the pulmonary artery. Bronchial flow and conductance (Qbr, Cbr), and pressure gradients (Pg; i.e. aortic minus right atrial, Pg_RAP; pulmonary artery, Pg_Ppa; and, left atrial (wedge) Pg_LAP) were derived from continuous records, after switching between downstream sites during and after moderately severe treadmill exercise (3.8 km.h(-1), for 1.7 min, 6 min recovery). The protocol was repeated after combined alpha1,alpha2-adrenoceptor/cholinoceptor blockade using phentolamine methanesulfonate and methscopolamine bromide. Bronchial flow fell in both receptor intact (INT) and (BL) blocked state. Pa rose in INT, but downstream pressures rose only 3.7 (RAP), 2.8 (Ppa) and 2.0 (LAP) mmHg (P for each < 0.05) in both INT and BL. Pg_RAP and Pg_Ppa did not rise, but Pg_LAP rose 4.0 mmHg (P < 0.05). In BL, Pa fell, as did Pg_RAP (7.0 mmHg, P < 0.05), Pg_Ppa (8.9 mmHg, P < 0.001), but Pg_LAP did not change. Thus, downstream pressures change by small amounts, and pressure gradients to RAP and Ppa sites do not change during moderately severe exercise in normal sheep. The fall in Qbr in INT is due to neural factors, but in BL is due to a fall in Pg. The relative rise in Pg_LAP in both INT and BL favours redistribution within total Qbr to the pulmonary capillary/vein/left atrium site.

Animals↗
PubMed2002

Pseudorapidity and centrality dependence of the collective flow of charged particles in Au+Au collisions at sqrt[s(NN)]=130 GeV.

This paper describes the measurement of collective flow for charged particles in Au+Au collisions at sqrt[s(NN)]=130 GeV using the PHOBOS detector at the Relativistic Heavy Ion Collider (RHIC). The measured azimuthal hit anisotropy is presented over a wide range of pseudorapidity (-5.0<eta<5.3) for the first time at this energy. The result, averaged over momenta and particle species, is observed to reach 7% for peripheral collisions at midrapidity, falling off with centrality and increasing |eta|. These results call into question the common assumption of longitudinal boost invariance over a large region of rapidity in RHIC collisions.

Journal Article↗
PubMed2002

Complete embedding and close step-sectioning of radical prostatectomy specimens both increase detection of extra-prostatic extension, and correlate with increased disease-free survival by stage of prostate cancer patients.

The objectives of this work were to evaluate the efficacy of controlled close step-sectioned and whole-mounted radical prostatectomy specimen processing in prediction of clinical outcome as compared to the traditional processing techniques. Two-hundred and forty nine radical prostatectomy (RP) specimens were whole-mounted and close step-sectioned at caliper-measured 2.2-2.3 mm intervals. A group of 682 radical prostatectomy specimens were partially sampled as control. The RPs were performed during 1993-1999 with a mean follow-up of 29.3 months, pretreatment PSA of 0.1-40, and biopsy Gleason sums of 5-8. Disease-free survival based on biochemical or clinical recurrence and secondary intervention were computed using a Kaplan-Meier analysis. There were no significant differences in age at diagnosis, age at surgery, PSA at diagnosis, or biopsy Gleason between the two groups (P<0.05). Compared with the non-close step-sectioned group, the close step-sectioned group showed higher detection rates of extra-prostatic extension (215 (34.1%) vs, 128 (55.4%), P<0.01), and seminal vesicle invasion (50 (7.6%) vs 35 (14.7%), P<0.01). The close step-sectioned group correlated with greater 3-y disease-free survival in organ-confined (P<0.01) and specimen-confined (P<0.01) cases, over the non-uniform group. The close step-sectioned group showed significantly higher disease-free survival for cases with seminal vesicle invasion (P=0.046). No significant difference in disease-free survival was found for the positive margin group (P=0.39) between the close step-sectioned and non-uniform groups. The close step-sectioned technique correlates with increased disease-free survival rates for organ and specimen confined cases, possibly due to higher detection rates of extra-prostatic extension and seminal vesicle invasion. Close step-sectioning provides better assurance of organ-confined disease, resulting in enhanced prediction of outcome by pathological (TNM) stage.

Adult↗
PubMed2001

Energy dependence of particle multiplicities in central Au+Au collisions.

We present the first measurement of the pseudorapidity density of primary charged particles in Au+Au collisions at root square[s(NN)] = 200 GeV. For the 6% most central collisions, we obtain dN(ch)/d(eta)/(/eta/<1) = 650+/-35(syst). Compared to collisions at root square[s(NN)] = 130 GeV, the highest energy studied previously, an increase by a factor of 1.14+/-0.05 at 90% confidence level, is found. The energy dependence of the pseudorapidity density is discussed in comparison with data from proton-induced collisions and theoretical predictions.

Journal Article↗
PubMed2001

Antilambda production in Au+Au collisions at 11.7A GeV/c.

We present results for antilambda and antiproton production in Au+Au collisions at 11.7 A GeV/c including spectra and extracted invariant yields for both species in central and peripheral collisions in the rapidity range 1.0<y<1.4. The antilambda yield increases from dN(Lambda;)/dy = 1.2(+0.7+0.2)(-0.6-0.2)x10(-3) in peripheral collisions to 19(+4+3)(-5-2)x10(-3) in central collisions. The direct antiproton yield is deduced from the measured total antiproton spectra to extract the ratio of antilambda-to-direct-antiproton production. The Lambda/p ratio near midrapidity increases from 0.26(+0.19+0.5)(-0.15-0.4) in peripheral collisions to 3.6(+4.7+2.7)(-1.8-1.1) in central collisions, a value larger than current theoretical estimates.

Journal Article↗
PubMed2001

Missense mutations in COL8A2, the gene encoding the alpha2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy.

Corneal clarity is maintained by its endothelium, which functions abnormally in the endothelial dystrophies, leading to corneal opacification. This group of conditions includes Fuchs' endothelial dystrophy of the cornea (FECD), one of the commonest indications for corneal transplantation performed in developed countries, posterior polymorphous dystrophy (PPCD) and the congenital hereditary endothelial dystrophies (CHED). A genome-wide search of a three-generation family with early-onset FECD demonstrated significant linkage with D1S2830 (Z(max) = 3.72, theta = 0.0). Refinement of the critical region defined a 6-7 cM interval of chromosome 1p34.3-p32 within which lies the COL8A2 gene. This encodes the 703 amino acid alpha2 chain of type VIII collagen, a short-chain collagen which is a component of endothelial basement membranes and which represented a strong candidate gene. Analysis of its coding sequence defined a missense mutation (gln455lys) within the triple helical domain of the protein in this family. Mutation analysis in patients with FECD and PPCD demonstrated further missense substitutions in familial and sporadic cases of FECD as well as in a single family with PPCD. This is the first description of the molecular basis of any of the corneal endothelial dystrophies or of mutations in type VIII collagen in association with human disease. This suggests that the underlying pathogenesis of FECD and PPCD may be related to disturbance of the role of type VIII collagen in influencing the terminal differentiation of the neural crest derived corneal endothelial cell.

Amino Acid Sequence↗
PubMed2001

Charged-particle pseudorapidity density distributions from Au+Au collisions at sqrt[s(NN)]=130 GeV.

The charged-particle pseudorapidity density dN(ch)/d eta has been measured for Au+Au collisions at sqrt[s(NN)] = 130 GeV at RHIC, using the PHOBOS apparatus. The total number of charged particles produced for the 3% most-central Au+Au collisions for /eta/<or=5.4 is found to be 4200+/-470. The evolution of dN(ch)/d eta with centrality is discussed, and compared to model calculations and to data from proton-induced collisions. The data show an enhancement in charged-particle production at midrapidity, while in the fragmentation regions, the results are consistent with expectations from pp and pA scattering.

Journal Article↗
PubMed2001

Ratios of charged antiparticles-to-particles near mid-rapidity in Au + Au collisions at sqrt[s(NN)]=130 GeV.

We have measured the ratios of antiparticles to particles for charged pions, kaons, and protons near mid-rapidity in central Au+Au collisions at sqrt[s(NN)] = 130 GeV. We observe / = 1.00+/-0.01(stat)+/-0.02(syst), / = 0.91+/-0.07(stat)+/-0.06(syst), and / = 0.60+/-0.04(stat)+/-0.06(syst). The / and / ratios give a consistent estimate of the baryo-chemical potential mu(B) of 45 MeV, a factor of 5-6 smaller than in central Pb+Pb collisions at sqrt[s(NN)] = 17.2 GeV.

Journal Article↗
PubMed2001

A prospective study of immunisation for a cohort of children.

AIMS: To determine rates of immunisation by 24 months of age, the number of times children were recalled and the cost of immunisation for a cohort of children in general practices in Wellington. METHODS: A prospective study of 979 children registered with 27 general practices. Children in the cohort were followed from 9-24 months old. Data collected included immunisation status, the number of times children were recalled and demographic data. RESULTS: At the end of the study period (when children reached 24 months of age) 803 (82%) remained with the practices and 176 (18%) had left. At 24 months 724 (74%) of the total cohort and 685 (85.3%) of registered children who stayed with the practice were fully immunised for the early childhood vaccinations. 54% of the cohort were fully immunised after a standard recall process. The average cost per child immunised was $13.33. CONCLUSION: It is possible to achieve high rates of full immunisation in children registered with a general practice using an effective system of facilitation and support.

Child, Preschool↗
PubMed2001

Axial structure of the heterotypic collagen fibrils of vitreous humour and cartilage.

We have compared the axial structures of negatively stained heterotypic, type II collagen-containing fibrils with computer-generated staining patterns. Theoretical negative-staining patterns were created based upon the "bulkiness" of the individual amino acid side-chains in the primary sequence and the D-staggered arrangement of the triple-helices. The theoretical staining pattern of type II collagen was compared and cross-correlated with the experimental staining pattern of both reconstituted type II collagen fibrils, and fibrils isolated from adult and foetal cartilage and vitreous humour. The isolated fibrils differ markedly in both diameter and composition. Correlations were significantly improved when a degree of theoretical hydroxylysine glycosylation was applied, showing for the first time that this type of glycosylation influences the negative-staining pattern of collagen fibrils. Increased correlations were obtained when contributions from types V/XI and IX collagen were included in the simulation model. The N-propeptide of collagen type V/XI and the NC2 domain of type IX collagen both contribute to prominent stain-excluding peaks in the gap region. With decreasing fibril diameter, an increase of these two peaks was observed. Simulations of the fibril-derived staining patterns with theoretical patterns composed of proportions of types II, V/XI and IX collagen confirmed that the thinnest fibrils (i.e. vitreous humour collagen fibrils) have the highest minor collagen content. Comparison of the staining patterns showed that the organisation of collagen molecules within vitreous humour and cartilage fibrils is identical. The simulation model for vitreous humour, however, did not account for all stain-excluding mass observed in the staining pattern; this additional mass may be accounted for by collagen-associated macromolecules.

Adult↗
PubMed2001

Baryon rapidity loss in relativistic Au + Au collisions.

An excitation function of proton rapidity distributions for different centralities is reported from AGS Experiment E917 for Au+Au collisions at 6, 8, and 10.8 GeV/nucleon. The rapidity distributions from peripheral collisions have a valley at midrapidity which smoothly change to distributions that display a broad peak at midrapidity for central collisions. The mean rapidity loss increases with increasing beam energy, whereas the fraction of protons consistent with isotropic emission from a stationary source at midrapidity decreases with increasing beam energy. The data suggest that the stopping is substantially less than complete at these energies.

Journal Article↗