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Biomedical subjects

C H Wilson

Publications and source records attributed to C H Wilson.

At least 19 recordsLinked to original sources

Non-heart-beating kidney transplantation: 6-year outcomes.

Non-heart-beating donor kidneys (NHBD) are being used to increase the donor pool due to the scarcity of cadaveric heart beating donors (HBD). We evaluated the long-term outcomes of renal transplantation using NHBD kidneys, comparing the first 100 NHBD kidneys transplanted at our facility to the next consecutive cadaveric HBD kidneys for graft survival, recipient survival, and quality of graft function. Recipient survival (P = .22) and graft survival (P = .19) at 6 years did not differ between recipients of NHBD (83%, 80%) and HBD (89%, 87%) kidneys. Quality of graft function using the mean glomular filtration rates were significantly lower in the NHBD group up to 3 months following discharge (41 +/- 2 vs 47 +/- 2, P = .007) but were then comparable up to 6 years following transplantation (43 +/- 5 vs 46 +/- 4, P = .55).

Adolescent↗

Preservation solutions for solid organ transplantation.

Solid organ transplantation was one of the greatest medical advances of the 20th century. Current preservation technology falls short of maintaining organs ex vivo in perpetuity. This review examines the biochemical basis of organ degradation in response to ischaemia, preservation solution composition and potential future organ preservation technology.

Calcium↗

Routine intraoperative ureteric stenting for kidney transplant recipients.

BACKGROUND: Major urological complications (MUCs) after kidney transplantation contribute to patient morbidity and compromise graft function. The majority arise from the vesico-ureteric anastomosis and present early after transplantation. Ureteric stents have been successfully used to treat such complications. A number of centres have adopted a policy of universal prophylactic stenting, at the time of graft implantation, to reduce the incidence of urine leaks and ureteric stenosis. Stents are associated with specific complications and some centres advocate a policy of only stenting selected anastomoses. OBJECTIVES: To examine the benefits and harms of routine ureteric stenting to prevent urological complications in kidney transplant recipients. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library), MEDLINE, EMBASE, reference lists of articles, books and abstracts and contacted companies, authors and experts to identify relevant randomised controlled trials (RCTs). SELECTION CRITERIA: All RCTs and quasi-RCTs were included in our meta-analysis. DATA COLLECTION AND ANALYSIS: Four reviewers assessed the trials for quality against four criteria (allocation concealment, blinding, intention-to-treat and completeness of follow-up). The primary outcome was the incidence of MUCs. Further outcomes of interest were graft and patient survival and the incidence of adverse events (urinary tract infection (UTI), haematuria, irritative symptoms, pain and stent migration). Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Seven RCTs (1154 patients) of low or moderate quality were identified. The incidence of MUCs was significantly reduced (RR 0.24, 95% CI 0.07 to 0.77, P = 0.02, NNT 13) by universal prophylactic stenting. This was dependent on whether the same surgeon performed, or was in attendance, during the operations. Two patients lost their grafts to infective urinary tract complications in the stented group. UTIs, in general, were more common in stented patients (RR 1.49, 95% CI 1.04 to 2.15) unless the patients were prescribed cotrimoxazole 480 mg/d: in which case the incidence was equivalent (RR 0.97, 95% CI 0.71 to 1.33). Stents appeared generally well tolerated, although trials using longer stents (>/= 20 cm) for longer periods (> 6 weeks) had more problems with encrustation and migration. AUTHORS' CONCLUSIONS: Routine prophylactic stenting reduces the incidence of MUCs. Trials comparing selective stenting and universal prophylactic stenting, whilst difficult to design and analyse, would address the unresolved quality of life and economic issues.

Hematuria↗

Randomized clinical trial of daclizumab induction and delayed introduction of tacrolimus for recipients of non-heart-beating kidney transplants.

BACKGROUND: Kidneys from non-heart-beating donors (NHBDs) have high rates of delayed graft function (DGF). Use of calcineurin inhibitors is associated with a reduction in renal blood flow, which may delay graft recovery from ischaemic acute tubular necrosis. METHODS: To assess whether daclizumab (DZB) could safely replace tacrolimus in the immediate postoperative period, patients were randomized to receive DZB induction and daily mycophenolate mofetil with steroids (DZB group) or standard tacrolimus-based triple therapy (control group). Tacrolimus was given to patients in the DZB group when the serum creatinine level dropped below 350 micromol/l. RESULTS: Fifty-one patients were recruited at two centres over a 2-year interval between 2000 and 2003. The overall rate of immediate function was 28 per cent (13 of 46 grafts), with the highest rate in recipients of machine-perfused kidneys treated with DZB (eight of 15 patients). CONCLUSION: Induction with DZB and delayed introduction of tacrolimus reduced the incidence of DGF in recipients of machine-perfused NHBD kidneys.

Adult↗

Prospective randomised trial of the use of Daclizumab in renal transplantation using kidneys from non heart beating donors.

OBJECTIVES: Transplantation using non-heart beating donors (NHBD) is one way of reducing the global kidney shortage. Unfortunately the large warm ischaemic insult sustained by the graft leads to a high rate of delayed graft function (DGF). We have investigated the use of a regimen utilising an II-2r blocker (DZB) in place of Tacrolimus for the initial post-operative immunosupression with the aim of reducing the incidence of DGF. METHODS: Prospective randomised controlled trial based in two NHBD UK centres (Leicester and Newcastle). 51 patients were enrolled over two years and randomised into two treatment arms: 1. DZB/MMF/Steroids (Tacrolimus started when creatinine dropped below 350 micromol/l) 2. Tacro/MMF/Steroids. RESULTS: There was one death, during the study period, in a patient who had had a non-functioning graft removed. The overall incidence of immediate function (IF) was higher than expected (28%), no significant difference was found in the incidence of immediate graft function between the two groups (35% group 1 and 22% group 2). Sub-group analysis however has shown a significant advantage for the delayed introduction of Tacrolimus for machine perfused grafts (IF: 53% vs 13%, chi2 p=0.015). There was no difference in the rate of rejection. CONCLUSIONS: The delayed introduction of Tacrolimus reduces the incidence of DGF in machine-perfused NHBD kidney transplantation.

Antibodies, Monoclonal↗

Weight increase during machine perfusion may be an indicator of organ and in particular, vascular damage.

OBJECTIVES: Hypothermic machine perfusion preservation has been shown to improve the outcome of renal grafts from non-heartbeating donors. We have noticed that organs gain a variable amount of weight during perfusion. METHODS: All grafts, whether used or discarded, were assessed with respect to their weight gain. Primary outcome measures were the results of viability testing. Secondary outcomes were early transplant variables including incidence and duration of delayed graft function and histological examination of protocol graft biopsies. RESULTS: Weight increase data was available on 97 grafts. There were no significant differences in weight gain between kidneys used and discarded (17% vs 20%). 14 patients received grafts which gained over 30% of their initial retrieval weight. There were no significant differences in secondary outcome measures between this group of recipients and patients who had received less "waterlogged" kidneys. Histological changes including endothelial inflammation and oedema were observed. CONCLUSIONS: Kidney grafts which have gained over 30% of weight on hypothermic machine perfusion preservation can be transplanted successfully. Complex interactions between the period of warm ischaemia, in situ flushing, perfusion pressures and perfusate probably lead to the phenomenon of excessive graft weight gain.

Blood Vessels↗

Establishing the right of the terminally ill to adequate palliative care: the litigation alternative.

The Bazelon Center For Mental Health Law in Washington, D.C., has undertaken a palliative care project to examine how litigation might be used to secure the rights of terminally ill patients to receive adequate palliative care, including the medications necessary to relieve the pain that often accompanies a final illness. One area of inquiry is the Medicare Hospice Benefit and the requirement that, to qualify for the benefit, a patient must have a prognosis of 6 months or less to live. A second major area of inquiry is regulatory restrictions on the prescription of opioids for pain relief of terminally ill patients and whether those restrictions improperly impede the physicians in their ability to engage in effective and appropriate pain management.

Journal Article↗

Familial clustering of end-stage renal disease in blacks with lupus nephritis.

The factors that determine a patient's susceptibility to specific target organ involvement in systemic lupus erythematosus (SLE) remain unknown. Lupus nephritis can be a particularly devastating complication, with an increased mortality and the risk of progressive renal damage resulting in end-stage renal disease (ESRD). This analysis was performed to determine whether renal disease aggregated in select families or was a sporadic complication in patients with SLE. We compared the family history of ESRD in 50 patients with SLE complicated by lupus nephritis with 37 controls who had SLE but lacked nephritis after a mean follow-up duration of more than 11 years. The frequency of relatives with ESRD in the lupus nephritis cases was compared with that in controls using Fisher's exact test (significance at P < or = 0.05). Fifty percent (25) of the 50 lupus nephritis patients were black and 50% (25) white, in contrast to 35% (13) and 65% (24) of the 37 lupus non-nephropathy controls, respectively. A first-, second-, or third-degree relative with ESRD was present in 16% (eight) of the 50 lupus nephritis cases and in 0% of the 37 SLE non-nephropathy controls (P = 0.019, Fisher's exact test, two-tail). Twenty-eight percent (seven) of the 25 black patients with lupus nephritis had relatives with ESRD compared with 0% of the 13 black lupus non-nephritis controls (P = 0.07). Only one of the eight relatives with ESRD had SLE or a collagen vascular disease. Lupus nephritis patients and the non-nephritis controls had similar ages (mean +/- SD: 38.5 +/- 10.0 years v 46.6 +/- 11.8 years; P = 0.28), family sizes (6.27 +/- 2.61 first-degree relatives v 6.35 +/- 3.25 first-degree relatives; P = 0.16), and duration of SLE (9.26 +/- 5.94 years v 11.35 +/- 6.43 years; P = 0.60). Familial clustering of ESRD was observed in black patients with SLE who had nephritis. This was unlikely to be related to differences in patient age, family size, or duration of SLE. This data, coupled with the known familial aggregation of ESRD in blacks with hypertensive and diabetic ESRD, supports the contention that genetic factors contribute to the familial clustering. The presence of relatives with etiologies of ESRD other than SLE suggests that there is an inherited susceptibility to progressive renal failure, independent of the etiology of ESRD.

Adult↗

Ketoprofen versus indomethacin in patients with rheumatoid arthritis: a multicenter double blind comparative study.

Oral ketoprofen (200-300 mg/day) and indomethacin (100-150 mg/day) were compared in a 12-week double blind study involving 140 patients with rheumatoid arthritis. The treatments were generally equally effective in most assessments, producing highly significant (p less than 0.01) improvements from baseline values within one week. Only isolated statistically significant differences (p less than 0.05) were detected between the 2 treatments: ketoprofen had a more pronounced effect than indomethacin in functional class (Weeks 1 and 12), swollen joint score (Week 1), and patients' global assessments (Week 12); indomethacin was significantly superior in improving grip strength at Week 4. The clinical significance of these statistically established differences may be questioned. The incidence of side effects, primarily gastrointestinal and neurologic, was also comparable in the 2 treatments.

Adult↗

Comparison of five assays for immune complexes in the rheumatic diseases. An assessment of their validity for rheumatoid arthritis.

Clinical assessment (disease activity, severity, and extraarticular manifestations) of 101 rheumatoid arthritis patients was correlated with several laboratory tests, including 5 immune complex assays: the bovine conglutinin, 125I-Clq binding, monoclonal rheumatoid factor inhibition, Raji cell, and staphylococci binding assays. Elevated disease activity indices were most closely associated with the presence of immune complexes detected by the 125I-Clq and staphylococci binding assays. There were significant but weak correlations between the level of disease activity and the level of immune complexes as measured by the bovine conglutinin, 125I-Clq binding, Raji cell, and staphylococci binding assays. Articular disease severity, as measured by anatomic stage, was discriminated by the bovine conglutinin, monoclonal rheumatoid factor inhibition, and staphylococci binding assays. Extraarticular manifestations were best discriminated by the Raji cell and staphylococci binding assays. We concluded that the sensitivity, specificity, predictive value, and overlap of the associations were not sufficient to warrant their wide use for the diagnosis and management of rheumatoid arthritis in individual patients. Conversely, the 125I-Clq and staphylococci binding assays were as good as the erythrocyte sedimentation rate and the IgG rheumatoid factor test (the 2 best of many examined) in assessing disease activity. Further prospective studies with these assays will determine their usefulness in following rheumatoid arthritis for a prolonged period.

Antigen-Antibody Complex↗

A single platelet aggregometric assay for pro-and antiaggregatory prostanoids.

A method is described for characterizing disaggregatory and proaggregatory prostanoids in a single assay. This "post-addition assay" consists of adding the test agent to PRP containing PGI2 (4-6 nM) 90 sec after an ADP challenge. The relative potencies of known inhibitors of ADP-induced aggregation were identical to the relative disaggregatory potencies determined by post-addition. The proaggregatory relative potencies for 16, 16-Me2-PGE2,PGE2,PGH2 and 11 alpha,9 alpha-epoxymethano-15 alpha-hydroxy-prostadienoic acid were 5.8 :2 : 1.8 : 1, respectively, revealing the significant thrombosis promoting activity of PGE2 and its analogs.

Adenosine Diphosphate↗

The subxiphoid approach to pericardial disease.

During the 36-month period from July, 1978, through July, 1981, 25 patients underwent a subxiphoid pericardial window procedure for diagnosis and therapy. Twelve patients were operated on for uremic pericarditis, 6 for malignancy, and 7 for etiological diagnosis of the pericarditis. All 12 patients with renal failure had enlarging effusions, despite aggressive dialysis. Eleven of the 12 are alive, free from recurrence, 3 to 36 months postoperatively. Six patients were operated on for suspected pericardial malignancy with hemodynamic compromise. Histological diagnosis was made from the pericardial tissue in all patients; only 1 patient lived more than 43 days following the procedure. In the group of 7 patients operated on for diagnosis, 4 were thought preoperatively to have tuberculous pericarditis. All 4 were treated with anti-tuberculosis chemotherapy and are asymptomatic, without evidence of calcification, 12 to 31 months postoperatively. This diverse group of patients demonstrates that the subxiphoid pericardial window is an effective approach for relief of uremic effusions and may adequately treat effusive tuberculous pericarditis when combined with multidrug chemotherapy. Patients with suspected malignant pericardial disease and hemodynamic compromise need to be carefully studied before an operative procedure is considered as a means of diagnosis and therapy.

Adult↗

Laser therapy of rheumatoid arthritis.

Thirty people with classical or definite rheumatoid arthritis received laser exposure to a Q-switch neodymium laser that operated at 1.06 micrometer with an output of 15 joules/cm2 for 30 nsec. One hand was lased at the proximal interphalangeal (PIP) and metacarpal phalangeal (MCP) joints, whereas the other hand was sham lased. The patient, physician, and occupational therapy evaluators did not know which hand was being lased. Twenty-one patients noted improvement of both their MCP and PIP joints of both hands during laser therapy. Twenty-seven noted improvement of their PIP joints and 26 noted improvement of the MCP joints during therapy. Heat, erythema, pain, swelling, and tenderness all improved with time in both hands, but the lased hand had more significant improvement in erythema and pain. There was also significant improvement in grasp and tip pressure on the lased side. The level of circulating immune complexes as measured by platelet aggregation decreased during lasing. The improvement may be related to laser exposure. The exact role that laser radiation has upon rheumatoid arthritis and its mechanism of action remain to be elucidated.

Adult↗

Synthesis and chiroptical characterization of prostacyclin diastereomers.

In the mercuri- and halo-cyclizations of PGF2 alpha methyl ester and its 11,15-bis(alpha- ethoxyethyl)-ether (or other protected forms) the exo-PGI1 derivative predominates independent of reagent and degree of protection of the PGF2 alpha sample used. Diastereomerically pure samples of exo- and endo-PGI1 and prostacycline (PGI2) were prepared. PGI0 epimers were prepared: catalytic hydrogenation of PGI2 Me ester provides exclusively the endo isomer. PGI2 methyl ester was found to be stable to extensive chromatography on silica, and to storage for at least a year in anhydrous ethanol at -20 degrees C. At pH 7.4 in 2:1 H2O:EtOH, the ester has a half-life in excess of 5 hr at 25 degrees C. A reproducible small scale (0.4-3 mg) synthesis of prostacyclin uses a modification of Whittaker's iodocyclization followed by DBN treatment. This procedure, developed with 15-3H-PGF2 alpha, proved widely applicable to PGF2 alpha analogs and diastereomers. The following prostacyclins (in the Me ester and Na salt forms) bearing the 5-en-6-yl ether unit were prepared in this way: ent-PGI2, rac-PGI2, 15-epi-PGI2, ent-15-epi-PGI2, 11-epi-PGI2, 8,9,12-epi-PGI2, E-PGI2, 13,14-dihydro-PGI2, and 13,14-dihydro-15-epi-PGI2. NMR comparisons for the methyl esters reveal that of the resonances (H-5,9,UU, 15) that appear at delta 4.0 +/- 0.6 ppm, the most deshielded is H-9 so long as the 5.6-olefin is Z. The 8R,9S-6,9-oxido-Z-5,6-ene unit is most readily characterized by its strong positive dichroic absorption at 210-230 nm. CD spectroscopy not only serves to confirm the presence of this unit in analogs, but also can be used for quantitative analysis of PGI2 solutions and for monitoring the rate of hydrolytic cleavage of these enol ethers.

Cyclization↗

On the multiplicity of platelet prostaglandin receptors. I. Evaluation of competitive antagonism by aggregometry.

Methods for the evaluation of competitive interactions at receptors associated with platelet activation and inhibition using aggregometry of human PRP have been developed. The evidence supports the suggestion that PGE1 and PGI2 share a common receptor for inhibition of platelet reactivity, but only a portion (if any) of the aggregation stimulation associated with PGE2 is the result of PGE2 binding (without efficacy) to this receptor. PGE2 (at .3-20 microM) is an effective antagonist of PGE1, PGI2, and PGD2 producing a shift of about one order of magnitude in the IC50-values obtained from complete aggregation inhibition dose response curves. The antagonism of PGD2 inhibition is particularly notable, 80 nM PGE2 levels are detectable. This and other actions of PGE2 indicate another platelet receptor for PGE2. PGE1 acts at both the PGE2 and PGI2 receptor. Other substances showing PGI2-like actions only at high doses (1-30 microM), display additive responses with PGI2 indicative of decreased affinity for the I2/E1 receptor and the absence of PGE2-like aggregation stimulation activity. PGI2 methyl ester has intrinsic inhibitory action not associated with in situ ester hydrolysis. The methyl ester is dissaggregatory showing particular specificity for inhibition of release and second wave aggregation.

Adenosine Diphosphate↗