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Biomedical subjects

A Jones

Publications and source records attributed to A Jones.

At least 487 records · Page 27Linked to original sources

Endocrine, pharmacokinetic and clinical studies of the aromatase inhibitor 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione ('pyridoglutethimide') in postmenopausal breast cancer patients.

The aromatase inhibitor, 'pyridoglutethimide' (PyG), has been shown previously to suppress serum oestrogen levels in postmenopausal breast cancer patients and to achieve clinical responses at a dose of 500 mg twice daily (b.d.). This report gives the results of a detailed pharmacokinetic and endocrine study of PyG in ten patients. Four doses were tested at intervals of 2 weeks in the following order: 200 mg b.d., 400 mg b.d., 800 mg b.d., 1200 mg b.d. Concentration-time profiles of serum levels of PyG were curvilinear in all patients probably reflecting a saturation of metabolic enzymes. During repeat-dosing metabolism was enhanced approximately 2-fold. Plasma levels of oestradiol were significantly suppressed by the lowest dose of PyG. Although higher doses appeared to achieve greater suppression this was not statistically significant in this small group of patients. There were no significant effects at any dose on the serum levels of cortisol, aldosterone, luteinising hormone, follicle stimulating hormone, prolactin, sex hormone binding globulin or thyroid stimulating hormone. There was a dose-related increase in 17 alpha-hydroxyprogesterone levels and a dose-related decrease in levels of dehydroepiandrosterone sulphate (DHAS). The androgens DHA, testosterone and androstenedione also were significantly suppressed with at least one of the doses of PyG. Synacthen tests did not support these changes being a result of inhibition of 17,20 lyase. It is possible that they are due to enhanced clearance of DHAS. Two patients experienced no toxicity throughout the study, whilst a total of four patients were withdrawn because of side-effects: one at 400 mg b.d., two at 800 mg b.d., and one at 1200 mg b.d. The most frequent side-effects were nausea and lethargy. One patient showed an objective response to treatment.

Aged↗

Antibiotic therapy, clinical features and outcome of 36 adults presenting to hospital with proven influenza: do we follow guidelines?

The impact of the 1989/1990 influenza epidemic on the Nottingham hospitals was assessed in a retrospective survey. Thirty-six cases of proven influenza were identified, 14 of whom died. Non-survivors were more likely to be confused, uraemic and to lack focal chest signs and symptoms. Antibiotic therapy both prior to admission and following hospitalization was not optimal and, in many cases, failed to follow previously published guidelines. Such guidelines need emphasis during influenza epidemics.

Adult↗

The dangers resulting from inaccurate computer-based operative records.

The accuracy of a computer-based recording system of operative procedures was audited at a major district general hospital. The system is supposed to provide accurate records of theatre activity, to allow for improved nursing resource allocation and provide surgeons with a basic record of their operations. Mistakes were present in the details of 27% of the cases entered. Such inaccuracies highlight a major danger to surgeons with regard to their accountability for operations attributed to them. Mistakes can only cause further problems with regard to audit and future resource allocation.

Documentation↗

A proposed minimal rheumatological screening history and examination. The joint answers back.

We have developed a rapid, reliable locomotor screening procedure to identify regional locomotor problems. An initial screen was tested in general medical inpatients and modified in the light of this experience. The revised screen was subsequently retested in a similar group of patients and new referrals to a rheumatology outpatient clinic. The revised screen proved sensitive, quick, and acceptable to both patients and doctors. Such a screen could readily be adopted by undergraduates: its routine use should improve detection and awareness of rheumatological problems and form the foundation for development of rheumatological clinical skills.

Adult↗

Addition of verapamil and tamoxifen to the initial chemotherapy of small cell lung cancer. A phase I/II study.

Based on experimental observations that verapamil and tamoxifen reverse multiple drug resistance, the authors investigated the feasibility of combining both agents with the initial chemotherapy of extensive small cell lung cancer. Overall, in a consecutive series of 58 patients the most important toxicity was myelosuppression, and there was a 24% rate of severe infections. Therapeutic results included 24% complete and 34% partial response rates, median time to disease progression of 32 weeks, and median survival of 46 weeks. In three consecutive cohorts of patients the dose of either tamoxifen or verapamil were escalated by 25% and 33%, respectively. The cohort of patients receiving verapamil 360 mg/day and tamoxifen 100 mg/day (level 2) had slightly more toxicity but also more responses than the other groups. Therefore, the authors recommend that these doses be used in controlled trials to confirm the promising results of their study.

Antineoplastic Combined Chemotherapy Protocols↗

Stimulus-specific effects of pentoxifylline on neutrophil CR3 expression, degranulation, and superoxide production.

The effects of pentoxifylline (Trental) on human neutrophil CR3 up-modulation, degranulation, and superoxide production were studied. We used the chemotactic peptide fMLP and the phorbol ester PMA as soluble stimuli, and beta-glucan particles as a CR3-specific solid phase stimulus of neutrophil superoxide production. Since neutrophils have adenosine A2 receptors, we compared effects of pentoxifylline to effects of adenosine, and we also looked at the effect of cytochalasin B, which breaks up actin filaments. Pentoxifylline inhibited both CR3 up-modulation and degranulation of myeloperoxidase and lysozyme. Pentoxifylline is a more potent inhibitor of fMLP- compared to PMA-induced degranulation, and is especially potent against superoxide production. While pentoxifylline is less potent than adenosine in its inhibition of fMLP-induced superoxide production, it is more potent in its inhibition of PMA- and beta-glucan particle-stimulated superoxide production. Cytochalasin B, which enhances degranulation and fMLP-stimulated superoxide production, was found to inhibit beta-glucan particle-stimulated superoxide production. These findings are consistent with the hypothesis that pentoxifylline can affect both the cytoskeletal architecture of unstimulated neutrophils and the activation and responses of neutrophils which involve actin polymerization and receptor-cytoskeletal interactions.

Adenosine↗