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Biomedical subjects

J Forbes

Publications and source records attributed to J Forbes.

At least 55 records · Page 3Linked to original sources

Visual performance and objectively measured grades of cataract. A correlation of methods designed for use in longitudinal trials.

Objective quantification of cataract and subjective assessment of visual performance are essential features of anticataract or cataractogenic drug trials. The constrains of a longitudinal trial require a compromise in contrast sensitivity measurement between sensitivity and speed. Such a system has been developed for use in longitudinal anticataract trials. An objective cataract assessment system has also been developed for these trials. Visual performance parameters and objectively measured grades of cataract using these systems were correlated in a group of patients with early lens opacities. Overall the correlation was poor in all three morphological types of cataract. Possible reasons for this and implications for future anticataract trials are discussed.

Aged↗

The surgery of early breast cancer.

This review highlights important issues for surgeons treating early breast cancer. The optimal use of ovarian ablation, the value and timing of radiotherapy for breast preservation, and axillary dissection are considered. New information on the importance of local surgery, even for older women, and the biology of small (up to 10 mm), screen-detected cancers has been recently reported. The value of support services for women having breast cancer surgery is stressed.

Breast Neoplasms↗

An evaluation of community antenatal care.

A study to ascertain how the community based antenatal services in the East End of Glasgow related to the guidelines set by a Working Party on Ante-Natal and Intrapartum Care (Royal College of Obstetricians and Gynaecologists, 1982) is reported. All community based clinics were visited and described. The socio-economic status of the sample population was defined and users' views and preferences sought. The women sampled were often socially and economically disadvantaged. Unemployment was high. They received their community antenatal care from midwives, general practitioners and consultants in both health centres and general practitioner surgeries. Women were generally satisfied with the care they received. Answers to more specific questions indicated, however, that more information and individualised care would be appreciated.

Adult↗

High-resolution proton and carbon-13 NMR of membranes: why sonicate?

We have obtained high-field (11.7-T) proton and carbon-13 Fourier transform (FT) nuclear magnetic resonance (NMR) spectra of egg lecithin and egg lecithin-cholesterol (1:1) multibilayers, using "magic-angle" sample spinning (MASS) techniques, and sonicated egg lecithin and egg lecithin-cholesterol (1:1) vesicles, using conventional FT NMR methods. Resolution of the proton and carbon-13 MASS NMR spectra of the pure egg lecithin samples is essentially identical with that of sonicated samples, but spectra of the unsonicated lipid, using MASS, can be obtained very much faster than with the more dilute, sonicated systems. With the 1:1 lecithin-cholesterol systems, proton MASS NMR spectra are virtually identical with conventional FT spectra of sonicated samples, while with 13C NMR, we demonstrate that most 13C nuclei in the cholesterol moiety can be monitored, even though these same nuclei are essentially invisible, i.e., are severely broadened, in the corresponding sonicated systems. In addition, 13C MASS NMR, spectra can again be recorded much faster than with sonicated samples, due to concentration effects. Taken together, these results strongly suggest there will seldom be need in the future to resort to ultrasonic disruption of lipid bilayer membranes in order to obtain high-resolution proton or carbon-13 NMR spectra.

Carbon Isotopes↗

Monitoring distributional assumptions and early stopping for a prospective clinical trial using Monte Carlo simulation.

We have applied the technique of Monte Carlo simulation to the determination of sample size for a partially completed clinical trial of chemotherapy for breast cancer. Simulations based on results observed after the entry of 243 patients in 2 years indicated a power greater than that predicted by the calculations made before the protocol was activated, and allowed a recommendation for an eventual trial closure earlier than would have been permitted by traditional methods. Both estimative and predictive approaches to the simulation of expected survival times for censored patients are presented. The use of simulation is recommended as an aid in reassessing the exact nature of the underlying survival distributions (as these affect the sample size calculations) and in optimizing stopping rules relating to patient accrual to a clinical trial in progress.

Breast Neoplasms↗

Drug resistance in clinical practice: patterns of treatment failure in patients receiving systemic therapy for advanced breast cancer.

Strategies for overcoming the causes of drug resistance should take account of the patterns of treatment failure seen in clinical practice. We have analysed the patterns of disease progression in 267 patients with advanced breast cancer receiving systemic therapy. First disease progression on therapy most commonly occurred in tissues involved by tumour at the commencement of treatment. However in 40% of patients, first documentation of disease progression included a tissue not previously known to contain metastatic disease. In only 3% of patients was this new tissue the central nervous system. This pattern of disease progression was not influenced by treatment type (i.e. endocrine or cytotoxic), tumour response to treatment, oestrogen receptor status, prior adjuvant cytotoxic treatment, or disease free interval. These results question the wisdom of always ceasing existing therapy and substituting new treatment when progressive disease is first documented.

Antineoplastic Agents↗

The pharmacokinetics of sulphasalazine in young and elderly patients with rheumatoid arthritis.

The clinical pharmacokinetics of enteric-coated sulphasalazine (Salazopyrin-EN) were studied after acute and chronic dosing in 20 patients with 'active' rheumatoid arthritis. 12 elderly (mean age 74.4 +/- 1 yr; range 71-83) and 8 young (mean age 40.5 +/- 1.4 yr; range 35-46) patients were given a single 2 g oral dose of sulphasalazine after an overnight fast. Serum and urine samples were collected at regular intervals over a 96 hour period for estimation of concentrations of sulphasalazine, sulphapyridine and its metabolites. This procedure was repeated after 17 days of continuous treatment with salazopyrin-EN 2 g daily in order to compare the drug's kinetics at 'steady-state'. Whilst the interindividual variation in kinetic parameters was large, age and acetylator status had a significant influence on a number of factors. The elimination half-life of sulphasalazine was prolonged in the elderly whilst renal clearance was increased in slow acetylators at 'steady-state'. The tmax and apparent volume of distribution of sulphapyridine were increased in the elderly after a single drug dosage but these differences disappeared with regular dosing. The Cmax, elimination half-life, 'steady-state' serum concentration, apparent volume of distribution and total clearance of sulphapyridine were all affected by acetylator status. We conclude that old age has only a minor effect on the body's handling of sulphasalazine and sulphapyridine but that acetylator phenotype plays a significant role in determining the 'steady-state' serum concentrations of sulphapyridine. This is likely to have practical implications with regard to some of the drug's adverse effects.

Acetylation↗

The external transcribed spacer and preceding region of Xenopus borealis rDNA: comparison with the corresponding region of Xenopus laevis rDNA.

We report sequence data from a cloned rDNA unit from Xenopus borealis, extending leftwards from the 18S gene to overlap a region previously sequenced by R. Bach, B. Allet and M. Crippa (Nucleic Acids Research 9, 5311-5330). Comparison with data from other species of Xenopus leads to the inference that the transcription initiation site in X.borealis is in the newly sequenced region and not, as was previously thought, in the region sequenced earlier. The X.borealis external transcribed spacer thus defined is some 612 nucleotides long, about 100 nucleotides shorter than in X.laevis. The X.borealis and X.laevis external transcribed spacers show a pattern of extensive but interrupted sequence divergence, with a large conserved tract starting about 100 nucleotides downstream from the transcription initiation site and shorter conserved tracts elsewhere. The regions in between the conserved tracts differ in length between the respective external transcribed spacers indicating that insertions and deletions have contributed to their divergence, as previously inferred for the internal transcribed spacers. Much of the overall length difference is in the region flanking the 18S gene, where there are also length microheterogeneities in X.laevis rDNA. As in X.laevis, the transcribed spacer sequences flanking the 18S gene in X.borealis contain no major tracts of mutual complementarity. The accumulated data on transcribed spacers in Xenopus render it unlikely that processing of ribosomal precursor RNA involves interaction between the regions flanking 18S RNA.

Animals↗

Treatment and survival on advanced breast cancer.

The final results of a clinical trial comparing endocrine with cytotoxic drug treatment for advanced breast cancer were analysed. Although cytotoxic treatment gave a significantly higher response rate with a remission duration comparable to that obtained with endocrine treatment, the sequence in which the two treatments were given did not appear to influence survival--except possibly in women with rapidly progressing disease, when cytotoxic treatment is preferred.

Antineoplastic Agents↗