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Biomedical subjects

D Porter

Publications and source records attributed to D Porter.

At least 19 recordsLinked to original sources

Comparing the rheology of native spider and silkworm spinning dope.

Silk production has evolved to be energetically efficient and functionally optimized, yielding a material that can outperform most industrial fibres, particularly in toughness. Spider silk has hitherto defied all attempts at reproduction, despite advances in our understanding of the molecular mechanisms behind its superb mechanical properties. Spun fibres, natural and man-made, rely on the extrusion process to facilitate molecular orientation and bonding. Hence a full understanding of the flow characteristics of native spinning feedstock (dope) will be essential to translate natural spinning to artificial silk production. Here we show remarkable similarity between the rheologies for native spider-dragline and silkworm-cocoon silk, despite their independent evolution and substantial differences in protein structure. Surprisingly, both dopes behave like typical polymer melts. This observation opens the door to using polymer theory to clarify our general understanding of natural silks, despite the many specializations found in different animal species.

Animals↗

Predicting the mechanical properties of spider silk as a model nanostructured polymer.

Spider silk is attractive because it is strong and tough. Moreover, an enormous range of mechanical properties can be achieved with only small changes in chemical structure. Our research shows that the full range of thermo-mechanical properties of silk fibres can be predicted from mean field theory for polymers in terms of chemical composition and the degree of order in the polymer structure. Thus, we can demonstrate an inherent simplicity at a macromolecular level in the design principles of natural materials. This surprising observation allows in depth comparison of natural with man-made materials.

Animals↗

Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised controlled trial.

BACKGROUND: Evidence for disease modifying activity of low dose corticosteroid treatment in rheumatoid arthritis is contradictory. Studies showing radiological benefit suggest that continued treatment is required to sustain the effect. OBJECTIVE: To evaluate the effect of low dose oral prednisolone in early rheumatoid arthritis on disease activity over two years. DESIGN: Double blind placebo controlled trial. METHODS: Patients with rheumatoid arthritis, duration <3 years (n = 167), were started on a disease modifying antirheumatic drug (DMARD; sulphasalazine) and allocated by stratified randomisation to prednisolone 7 mg/day or placebo. Primary outcome measure was radiological damage, assessed by the modified Sharp method. Clinical benefit was a secondary outcome. A proactive approach to identifying and treating corticosteroid adverse events was adopted. Patients who discontinued sulphasalazine were offered an alternative DMARD. RESULTS: 90 of 257 patients eligible for the study refused to participate (more women than men). Of those enrolled, 84% were seropositive for rheumatoid factor, median age 56 years, median disease duration 12 months, female to male ratio 1.8:1. Prednisolone was given to 84 patients; of these 73% continued prednisolone and 70% sulphasalazine at 2 years. Of the 83 patients on placebo, 80% continued placebo and 64% sulphasalazine at 2 years. There were no significant differences in radiological score or clinical and laboratory measures at 0 and 2 years. CONCLUSIONS: Low dose prednisolone conferred no radiological or clinical benefit on patients maintained on a DMARD over two years. Low dose corticosteroids have no role in the routine management of rheumatoid arthritis treated with conventional disease modifying drugs.

Adult↗

Phenytoin toxicity due to fluoropyrimidines (5FU/capecitabine): three case reports.

Interactions between phenytoin and the fluoropyrimidine derivatives, 5 fluorouracil (5FU) and capecitabine, are not commonly documented or widely recognised. As more people with significant medical comorbidities are now being considered for chemotherapy, it is increasingly likely that people receiving phenytoin will be prescribed treatment with fluoropyrimidines. We present two cases of clinical phenytoin toxicity occurring after starting treatment with 5-fluorouracil/folinic acid (5FU/FA) and a third who developed clinical phenytoin toxicity after starting capecitabine (an orally administered prodrug of fluorouracil).

Adenocarcinoma↗

Acute renal failure complicating HELLP syndrome, SLE and anti-phospholipid syndrome: successful outcome using plasma exchange therapy.

Renal disease is very common in patients with systemic lupus erythematosis (SLE) and it may emerge during pregnancy or the post-partum period. Patients with anti-phospholipid syndrome (APS)are also at risk of renal disease. We present a case of acute renal failure in the post-partum period in a patient with SLE and APS. This case illustrates the potential difficulties in reaching a diagnosis in such a patient. It also illustrates the complexities of management and the potential interactions between SLE, Haemolysis, elevated liver enzymes and low platelets syndrome, thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome and APS. We also review the role of plasma exchange therapy in managing our patient.

Acute Kidney Injury↗

Measures of intermittency in driven supersonic flows.

Scaling exponents for structure functions of the velocity, density, and entropy are computed for driven supersonic flows for rms Mach numbers of order unity, with numerical simulations using the piecewise parabolic method algorithm on grids of up to 512(3) points. The driving is made up of either one or three orthogonal shear waves. In all cases studied, the compressible component of the velocity in the statistically steady regime is weaker than its solenoidal counterpart by roughly a factor of 6. Exponents for the longitudinal component of the velocity are comparable to what is found in the incompressible case and appear insensitive to the presence of numerous shocks. Scaling exponents of the transverse components of the velocity are comparable to those for the longitudinal component. Density and entropy structure functions display strong departures from linear scaling. Finally, the scaling of structure functions of the energy transfer is also given and compared with the Kolmogorov refined similarity hypothesis.

Journal Article↗

Identification of amplified clonal T cell populations in the blood of patients with chronic graft-versus-host disease: positive correlation with response to photopheresis.

Chronic graft-versus-host disease (cGVHD) is a multiorgan disorder with skin manifestations resembling scleroderma. Since photopheresis, a treatment that induces an anticlonotypic immune response, has proven to be effective in both cutaneous T cell lymphomas with circulating clonal T cells and in cGVHD, we have searched for circulating clonal T cell populations in patients with cGVHD, and determined whether T cell clonality in the blood is associated with therapeutic response. We screened blood samples from 27 patients after HLA-matched allogeneic bone marrow transplantation (allo-BMT), 10 without cGVHD and 17 with extensive cGVHD, for clonal T cell receptor gamma (TCR gamma) gene rearrangements using fluorescent-based polymerase chain reaction (PCR) and automated high-resolution capillary electrophoresis. Amplified populations of clonal T cells with unique TCR gamma gene rearrangements were found in six of 10 (60%) allo-BMT patients without cGVHD and 13 of 17 (76.5%) allo-BMT patients with cGVHD (P = 0.41), as compared to none of 10 (0%) healthy controls. Twelve patients with cGVHD were treated by photopheresis, and the presence of amplified populations of clonal T cells was found to be associated with a cutaneous response to photopheresis, as eight of eight (100%) clone-positive vs none of four (0%) clone-negative patients experienced a clinically significant cutaneous response to treatment (P = 0.001). Our findings suggest that patients with cGVHD that have detectable expanded clonal T cell populations in their peripheral blood, may be more likely to respond to treatment by photopheresis.

Adult↗

Dose resolution in radiotherapy polymer gel dosimetry: effect of echo spacing in MRI pulse sequence.

In polymer gel dosimetry using magnetic resonance imaging, the uncertainty in absorbed dose is dependent on the experimental determination of T2. The concept of dose resolution (Dpdelta) of polymer gel dosimeters is developed and applied to the uncertainty in dose related to the uncertainty in T2 from a range of T4 encountered in polymer gel dosimetry. Dpdelta is defined as the minimal separation between two absorbed doses such that they may be distinguished with a given level of confidence, p. The minimum detectable dose (MDD) is Dpdelta as the dose approaches zero. Dpdelta and the minimum detectable dose both give a quantifiable indication of the likely practical limitations and usefulness of the dosimeter. Dpdelta of a polyacrylamide polymer gel dosimeter is presented for customized 32-echo and standard multiple-spin-echo sequences on a clinical MRI scanner. In evaluating uncertainties in T2, a parameter of particular significance in the pulse sequence is the echo spacing (ES). For optimal results, ES should be selected to minimize Dpdelta over a range of doses of interest in polymer gel dosimetry.

Biophysical Phenomena↗

Comparative study of intramuscular gold and methotrexate in a rheumatoid arthritis population from a socially deprived area.

OBJECTIVE: To compare the risk-benefit ratio of intramuscular gold (gold sodium thiomalate (GST)) and methotrexate (MTX) in a population with rheumatoid arthritis (RA) from a deprived area. METHODS: Patients with active RA were randomly assigned to open treatment with GST or MTX. Clinical and laboratory assessment was performed at 0, 12, 24, and 48 weeks. Results were analysed on an intention to treat basis. RESULTS: 141 patients were recruited-72 were randomly allocated to GST and 69 to MTX. There were no statistically significant differences found in either the clinical or demographic variables at baseline. At 48 weeks 31 (43%) patients continued to receive GST and 43 (62%) MTX. The median MTX dose achieved was 10 mg. Gold caused significantly more withdrawals for toxicity (43% GST v 19% MTX, p=0.0026, log rank test). Both groups experienced a significant improvement in erythrocyte sedimentation rate, C reactive protein, Ritchie Articular Index, and pain score by 24 weeks (p<0.001, Friedman test). Although a trend towards an improved Health Assessment Questionnaire (HAQ) score and global wellbeing was seen in both groups, this did not reach statistical significance. No differences in efficacy were found when the two groups were compared (Mann-Whitney). CONCLUSION: GST and low dose MTX showed equivalent efficacy, but toxicity was more common in patients treated with GST. GST, although more toxic, remains a useful alternative for patients in whom MTX is contraindicated.

Aged↗

Resistance training improves single muscle fiber contractile function in older women.

The purpose of this study was to 1) examine single cell contractile mechanics of skeletal muscle before and after 12 wk of progressive resistance training (PRT) in older women (n = 7; 74 +/- 2 yr) and 2) to compare these results to our previously completed single cell PRT work with older men (n = 7; 74 +/- 2 yr) (Trappe S, Williamson D, Godard M, Porter D, Rowden G, and Costill D. J Applied Physiol 89:143--152, 2000). Knee extensor PRT was performed 3 days/wk at 80% of one-repetition maximum. Muscle biopsies were obtained from the vastus lateralis before and after the PRT. Chemically skinned single muscle fibers (n = 313) were studied at 15 degrees C for peak tension (P(o)), unloaded shortening velocity (V(o)), and power. Due to the low number of hybrid fibers identified post-PRT, direct comparisons were limited to MHC I and IIa fibers. Muscle fiber diameter increased 24% (90 +/- 2 to 112 +/- 6 microm; P < 0.05) in MHC I fibers with no change in MHC IIa fibers. P(o) increased (P < 0.05) 33% in MHC I (0.76 +/- 0.04 to 1.01 +/- 0.09 mN) and 14% in MHC IIa (0.73 +/- 0.04 to 0.83 +/- 0.05 mN) fibers. Muscle fiber V(o) was unaltered in both fiber types with PRT. MHC I and IIa fiber power increased (P < 0.05) 50% [11 +/- 2 to 17 +/- 2 microN. fiber length (FL). s(-1)] and 25% (40 +/- 8 to 51 +/- 6 microN. FL. s(-1)), respectively. However, when peak power was normalized to cell size, no pre- to postimprovements were observed. These data indicate that PRT in elderly women increases muscle cell size, strength, and peak power in both slow and fast muscle fibers, which was similar to the older men. However, in contrast to the older men, no change in fiber V(o) or normalized power was observed in the older women. These data suggest that older men and women respond differently at the muscle cell level to the same resistance-training stimulus.

Aged↗

Profile of cognitive functioning in women with the fragile X mutation.

Two studies tested the specificity of the neurocognitive profile of women with fragile X syndrome (FXS). First, women with an FXS full mutation were compared with women with a premutation and women without FXS who grew up in FXS families. Women with FXS had a significantly lower IQ than the other groups, and analyses of subtest profiles showed they had a relative weakness on Arithmetic and strength on Picture Completion. Women with FXS performed worse than the other groups on executive function, spatial ability, and visual memory. Next, women with FXS were compared with women without FXS matched on age and IQ. A similar IQ profile was found, but women with FXS were worse than controls only on executive function. The authors also examined which neurocognitive indices were related to the underlying biology of the disorder. Overall, the results indicated that executive rather than visuospatial deficits were primary in the neurocognitive profile of FXS.

Adolescent↗

Minocycline induced lupus: case series in the West of Scotland.

OBJECTIVE: To describe the clinical symptoms and serology of drug-induced lupus in patients treated with the semisynthetic tetracycline derivative, minocycline. METHODS: For a 5-year period, all consultant rheumatologists and dermatologists in the West of Scotland were asked to report any suspected cases of a lupus-like syndrome to one center. Twenty cases were identified on the basis of arthritis, positive antinuclear factor and at least one other extraarticular feature following treatment for acne with minocycline. Case histories were reviewed to determine any demographic, clinical, or serological correlations. RESULTS: Minocycline had been prescribed for a mean of 25 months for the 20 patients identified with drug-induced lupus; 15 were female, 5 were male with a mean age of 24 years. All patients had arthritis and most had at least one other extraarticular feature including lethargy, myalgia, fevers, Raynaud's phenomenon, abdominal pain, and butterfly rash. None had renal involvement. All symptoms resolved at a mean of 15.7 weeks after discontinuation of minocycline treatment. CONCLUSIONS: Minocycline is widely used in the treatment of acne and increasingly in the treatment of rheumatic diseases. Although the absolute risk of developing drug-induced lupus is relatively low, it has been estimated that current use of minocycline is associated with an 8.5 fold increased risk of developing a lupus-like syndrome. Prescribing physicians must be vigilant for any of the characteristic symptoms to avoid unnecessary morbidity, investigations, and therapy.

Acne Vulgaris↗

Donor leukocyte infusions in acute lymphocytic leukemia.

Donor leukocyte infusion (DLI) has well-documented activity in CML but the role of DLI in other diseases is less well defined. To evaluate the strategy in acute lymphocytic leukemia (ALL) we evaluated 44 ALL patients from 27 centers who were treated with DLI. Patients with persistent or recurrent disease received DLI from the original marrow donor (30 matched related, four mismatched family, and 10 matched unrelated). Chemotherapy was given before DLI to 28 patients. Of 15 patients who received no pre-DLI chemotherapy, two achieved complete remissions, lasting 1112 and 764+ days. In four patients who received DLI as consolidation of remission induced by chemotherapy or immunosuppression-withdrawal, duration of remission post DLI was 65, 99, 195 and 672+ days. Of 25 patients who received DLI in the nadir after chemotherapy, 13 survived > or =30 days post DLI but did not achieve remission, seven died within less than 30 days post DLI, and five entered remissions that lasted 42, 68, 83, 90, 193 days. Seven patients who did not respond to the initial DLI received a second DLI; none of these patients attained durable remission. Eighteen of 37 evaluable patients developed acute GVHD and five of 20 evaluable patients developed chronic GVHD. Overall actuarial survival is 13% at 3 years. In conclusion, DLI has limited benefit in ALL. New approaches are needed in this group of patients.

Actuarial Analysis↗

Donor leukocyte infusions for multiple myeloma.

Donor leukocyte infusion (DLI) has well-documented activity in CML, but the role of DLI in other diseases is less well defined. To evaluate the strategy in multiple myeloma (MM) we evaluated 25 MM patients from 15 centers who were treated with DLI. Patients with persistent or recurrent disease after allogeneic BMT received DLI from the original marrow donor (23 matched related, one mismatched family, and one matched unrelated). Chemotherapy was given before DLI in three patients. Two of 22 patients responded completely to DLI alone and three patients responded to the combination of DLI and chemotherapy. Nine patients who had not had sufficient disease control after DLI were given additional DLIs; five of these patients had either complete (two) or partial (three) responses. Thirteen of 25 evaluable patients developed acute GVHD and 11 of 21 evaluable patients developed chronic GVHD; all responders developed GVHD. No patients developed post-DLI pancytopenia. Four patients had responses which lasted >1 year after DLI, three patients had responses which lasted <1 year, and three patients had ongoing responses but with follow-up <1 year. In conclusion, DLI has anti-myeloma activity but the strategy is limited by no response or short duration of response in a significant percentage of patients and by significant GVHD in the majority of the responders.

Adult↗