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Biomedical subjects

J Fletcher

Publications and source records attributed to J Fletcher.

At least 343 records · Page 19Linked to original sources

Ifosfamide and mitoxantrone (I-M) in relapsed and refractory high grade non-Hodgkin's lymphoma and Hodgkin's disease.

Fifty-five patients, initially diagnosed as having advanced high grade non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first-line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three-weekly intervals. Of 32 patients with NHL evaluable for response, 10 (31 per cent) achieved complete remission and five partial remission, giving an overall response rate of 47 per cent. Two patients subsequently went on to bone marrow transplant (BMT)--one allogeneic and the other autologous. Of 17 patients with HD evaluable for response, six (35 per cent) achieved complete remission and six partial remission, giving an overall response rate of 71 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. Given the need to offer alternative treatment of patients in these categories, this combination (I-M) is clearly of value in relapsed patients especially where therapeutic options are limited because of previous multi-drug treatment.

Adolescent↗

Twin-track studies of ifosfamide and mitoxantrone (I-M) in recurrent high grade non-Hodgkin's lymphoma and Hodgkin's disease. Yorkshire Regional Lymphoma and Central Lymphoma Groups.

Fifty-seven patients, initially diagnosed as having advanced high grade non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first-line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three-weekly intervals. Of 33 patients with NHL evaluable for response, 10 (30 per cent) achieved complete remission and six partial remission, giving an overall response rate of 48 per cent. Two patients subsequently went on to bone marrow transplant (BMT)--one allogeneic and the other autologous. Of 18 patients with HD evaluable for response, seven (39 per cent) achieved complete remission and six partial remission, giving an overall response rate of 72 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. The possibility of increasing the safety of the regimen by increasing the time of infusion to 72 h is discussed. Given the need to offer alternative treatment to patients in these categories, this combination (I-M) is of value in relapsed patients, especially where options are limited because of previous multi-drug treatment. Remissions may not be prolonged but allow the effective application of additional intensive treatment including bone marrow transplantation.

Adolescent↗

The tunnelling conductance of molecularly ordered metalloprotein arrays.

Metalloproteins can be self-assembled in molecularly ordered, electrochemically addressable arrays. We report here on a study of the transport characteristics of the blue copper protein, azurin, from Pseudomonas aeruginosa, by a combination of electrochemical and scanning probe techniques (scanning tunnelling microscopy and conducting atomic force microscopy). Redox-switchable chemisorbed molecular arrays can be formed from both wild-type and mutant proteins using the strong affinity of cysteine residue thiolates for pristine gold surfaces. The molecular transconductance of single protein molecules within these arrays has been studied under controllable conditions where it has been additionally possible to resolve the effects of protein mechanical perturbation. Although tunnelling appears to be non-resonant and adequately explained through the use of a square barrier model, under some conditions the contribution of the redox-active copper centre to conductance is resolvable.

Azurin↗

Effect of unilateral nephrectomy of the localization of aortic sudanophilic lesions in cholesterol-fed rabbits.

The method of polar coordinate mapping of lesions on the aortic wall around orifices was used to study the effect of unilateral nephrectomy on sudanophilic lesions in rabbits. Four groups of six rabbits each were studied. Group I had a right nephrectomy with a short renal artery stump. Group II had a sham right nephrectomy. Group III had a left nephrectomy with a short renal artery stump and Group IV a sham left nephrectomy. All groups were allowed to recover for one week and were then fed rabbit chow enriched with 2% cholesterol and 6% corn oil for a four-week period. Groups I and III showed a marked alteration in lesions around the stump with both proximal and distal peaks. Group I also showed the development of skewing of the left renal lesion to the left, presumably because of a change in aortic flow due to removal of the proximal right renal flow. The right renal artery had a lesion skewed to the right; this was not altered by left nephrectomy and was probably due to coeliac flow. The data provides strong evidence that sudanophilic lesions in rabbit aortas are altered by local flow disturbances.

Animals↗

Tissue localization and chromosomal assignment of a serum protein that tracks the cystic fibrosis gene.

The basic gene defect in the autosomal recessive disorder cystic fibrosis has not been identified, and no firm linkage of the disorder to any other marker has been reported. However, a serum protein abnormality present in unaffected heterozygotes as well as in affected homozygotes has been described, and immunological quantitation of this protein, termed cystic fibrosis antigen, allows the three genotypes to be distinguished. We show here that an immunologically indistinguishable protein is present at high concentrations in granulocytes from normal and cystic fibrosis individuals as well as in myeloid leukaemia cells. Somatic cell hybrids between the mouse myeloid stem-cell line WEHI-TG and myeloid leukaemia cells express cystic fibrosis antigen only when human chromosome I is present.

Blood Proteins↗

A three-part study to investigate the incidence and potential etiologies of tadalafil-associated back pain or myalgia.

The potential mechanisms underlying back pain and/or myalgia experienced by men taking tadalafil were investigated. An integrated analysis of 10 placebo-controlled tadalafil clinical trials (N=1846) showed that the incidence of back pain and/or myalgia was 9.4% in patients receiving tadalafil 10 mg (N=394), 8.3% in patients receiving tadalafil 20 mg (N=883) and 3.7% in placebo-treated patients (N=569). One (0.3%) patient receiving tadalafil 10 mg, six (0.7%) patients receiving tadalafil 20 mg, and no patients receiving placebo discontinued treatment due to back pain and/or myalgia. In a prospective study in healthy volunteers, no substantial changes were observed in laboratory markers indicative of inflammation or muscle damage, and tadalafil did not affect renal plasma flow nor produce lumbar or gluteal myositis by positron emission tomography scan or magnetic resonance imaging. Although the mechanism of back pain and/or myalgia remains unknown, these events appear to be self-limiting and a general effect of phosphodiesterase 5 inhibition.

Adolescent↗