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Biomedical subjects

R Barrington

Publications and source records attributed to R Barrington.

12 recordsLinked to original sources

Are we overusing blood transfusing after elective joint replacement?--a simple method to reduce the use of a scarce resource.

OBJECTIVES: To determine the proportion of patients who received a blood transfusion after joint replacement, and to devise a simple method to ensure patients were transfused based on strict clinical and haematological need. DESIGN: Prospective audit over 2 years. PATIENTS AND METHODS: The study group was 151 patients who underwent total hip and knee arthroplasty in a typical district general hospital (Kettering) over a 2-year period. They were divided into three consecutive groups. Current practice was audited (producing the first group of 62 patients) and transfusion rates were compared to regional figures. Local guidelines were drawn up. A form was introduced on which the indications for any transfusion had to be documented prior to transfusion of the blood. This was designed to encourage transfusion only on strong clinical grounds or an haemoglobin (Hb) level < 8 g/dl. Transfusion practice was then re-audited (producing the second group of 44 patients) to assess whether practice had improved. A year later, all relevant staff were reminded by letter of the guidelines. The process was then re-audited (producing the third group of 45 patients) again to determine whether practice remained improved or not. RESULTS: In the first audit (current practice) of 62 patients, the overall transfusion rate was 71%, with a higher rate in the hip replacement group (84%) ordered mainly by anaesthetic staff. Ward staff were reluctant not to transfuse patients whose Hb level fell below 10 g/dl. In the second audit, the transfusion rate fell by nearly 50% to 37%, with almost identical figures for knee and hip replacement. In the third audit of 45 patients, a year later, the transfusion rate was 40% overall. CONCLUSIONS: Patients were being transfused routinely, generally without good clinical evidence of benefit to the patient. The audit process was successful in instituting change for the better in blood transfusion practice for elective joint replacement. The improved practice can be largely maintained provided staff are regularly reminded of appropriate guidelines and encouraged to transfuse for clinical need only. For absolute adherence to guidelines, we would recommend a compulsory form system be introduced for transfusion in the per-operative period, to ensure blood transfusion is only given when absolutely necessary.

Arthroplasty, Replacement, Hip↗

The role of complement in inflammation and adaptive immunity.

Major advances in our understanding of the immunobiology of complement were made within the past 5 years primarily due to the development of gene-targeting technology. New strains of mice bearing specific deficiencies in serum complement proteins or their receptors were developed using this approach. Characterization of these mice has provided new and exciting insights into the biology of the complement system. In this review, we discuss recent results on two important aspects of the complement system, i) host protection and inflammation, and ii) regulation of B lymphocytes of adaptive immunity. While these two roles appear distinct, they are linked. We discuss how natural antibody and classical pathway complement work together in host protection against bacterial infection on the one hand but, on the other, they co-operate to induce inflammation as observed in reperfusion injury. Significantly, the lymphocytes that produce natural antibody, the B-1 lymphocytes, are regulated in part by the complement system.

Animals↗

Bisphosphonates in the prevention and treatment of glucocorticoid-induced osteoporosis.

OBJECTIVE: To summarize the literature concerning the use of bisphosphonates in the prevention and treatment of corticosteroid-induced osteoporosis and make recommendations concerning the proper use of these agents. SEARCH STRATEGIES: We conducted a literature search to identify studies in the English language concerning the use of bisphosphonates in the prevention or treatment of corticosteroid-induced osteoporosis using the MEDLINE, CURRENT CONTENTS, and HEALTHSTAR electronic databases, bibliographies of selected citations, and recent meeting abstracts. SELECTION CRITERIA: We included randomized controlled trials evaluating the use of oral bisphosphonates in adults by central dual X-ray absorptiometry. DATA COLLECTION AND ANALYSIS: We assessed the methodologic quality of the trials using the Jadad criteria. Data were collected concerning bone mineral density (BMD) changes in multiple areas, fracture rates, safety, and tolerability. MAIN RESULTS: Bisphosphonates generally increased BMD at the lumbar spine. Data were less clear concerning changes in the femoral area. Little information exists about the ability of bisphosphonates to reduce fracture risk in patients with corticosteroid-induced osteoporosis. Postmenopausal women seemed to receive the most benefit. CONCLUSIONS: Bisphosphonates significantly increased BMD in patients at risk for corticosteroid-induced bone loss. However, there is a sparsity of data concerning the ability of these agents to affect the clinically important outcome of fracture rate reduction, especially among premenopausal women in whom fractures are rare within the first year or 2 of exposure to corticosteroids. Long-term studies powered to detect fracture risk reduction are needed as well as comparative trials with bisphosphonates and other agents.

Adult↗

A Phase I and pharmacokinetic study of temozolomide and cisplatin in patients with advanced solid malignancies.

Temozolomide (TMZ) is an oral imidazotetrazinone that is spontaneously converted to 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC) at physiological pH. MTIC methylates DNA at the O6 position of guanine, although this lesion may be repaired by the enzyme O6-alkylguanine-DNA alkyltransferase (AGAT). In this study, TMZ was combined with cisplatin (CDDP), because both agents have single-agent activity against melanoma and other tumor types. Additionally, CDDP has been shown to inactivate AGAT, and subtherapeutic concentrations of CDDP have been shown to increase the sensitivity of leukemic blasts to TMZ. This Phase I study sought to determine the toxicities, recommended dose, and pharmacological profile of the TMZ/CDDP combination. Patients were treated with oral TMZ daily for 5 consecutive days together with CDDP on day 1 (4 h after TMZ) every 4 weeks at the following TMZ (mg/m2/day)/CDDP (mg/m2) dose levels: 100/75, 150/75, 200/75, and 200/100. Plasma samples were obtained on days 1 and 2 to evaluate the pharmacokinetic parameters of TMZ alone and in combination with CDDP. Fifteen patients received a total of 44 courses of TMZ/CDDP. The principal toxicities of the regimen consisted of neutropenia, thrombocytopenia, nausea, and vomiting, which were intolerable in two of six new patients treated at the 200/100 mg/m2 dose level. Of five patients receiving 17 courses at the next lower dose level (200/75 mg/m2), none experienced dose-limiting toxicity. Antitumor activity was observed in patients with non-small cell lung cancer, squamous cell carcinoma of the tongue, and leiomyosarcoma of the uterus. Pharmacokinetic studies of TMZ revealed the following pertinent parameters (mean +/- SD): time to maximum plasma concentration (Tmax) = 1.1+/-0.6 h (day 1) and 1.7+/-0.9 h (day 2); elimination half-life (t1/2) = 1.74+/-0.22 h (day 1) and 2.35+/-0.70 h (day 2); and clearance (Cl(s)/F) = 115+/-27 ml/min/m2 (day 1) and 141+/-109 ml/min/m2 (day 2). TMZ drug exposure, described by the area under the plasma concentration-time curve (AUCinfinity) and the maximum plasma concentration (Cmax), was similar on days 1 and 2. On the basis of these results, the recommended doses for Phase II clinical trials are TMZ 200 mg/m2/day for 5 days with 75 mg/m2 CDDP on day 1, every 4 weeks. The addition of CDDP did not affect the tolerable dose of single-agent TMZ (200 mg/m2/day x 5 days), nor did it substantially alter the pharmacokinetic behavior of TMZ.

Adult↗

A phase I clinical and pharmacokinetic study of the angiogenesis inhibitor, tecogalan sodium.

BACKGROUND: Tecogalan sodium is an angiogenesis inhibitor isolated from a sulfated polysaccharide produced by the bacterium Arthrobacter. The antiangiogenic effect of tecogalan sodium is thought to be mediated by the inhibition of binding of basic fibroblast growth factor to cellular receptors. PATIENTS AND METHODS: A phase I study was conducted in thirty-three patients with refractory malignancies, including AIDS-associated Kaposi's sarcoma. Patients received a single i.v. infusion every three weeks with the infusion duration ranging from one to twenty-four hours. Seven different dosage levels were studied (125, 185, 240, 300, 390, 445, and 500 mg/m2). RESULTS: The primary dose-limiting toxicity was prolongation of the activated partial thromboplastin time with peak times being between 1.0-4.0 times the upper limit of normal. This toxicity was ameliorated at a given dose level by prolonging the infusion time. Other common toxicities included fever (40%) and rigors (31%) which were well controlled with acetominophen and meperidine. The serum half-life of tecogalan sodium was between 1-1.5 hours and < 25% of unchanged drug was excreted in the urine. CONCLUSIONS: The recommended phase II dose of tecogalan sodium on this schedule is 390 mg/m2 over 24 hours. Other schedules including continuous administration should be investigated to maximize the efficacy of this novel angiogenesis inhibitor.

Antineoplastic Agents↗

HLA antigens in Tlingit Indians with rheumatoid arthritis.

HLA-DR4 has been described in association with rheumatoid arthritis (RA) in multiple populations. We have studied HLA antigens in Alaskan Tlingit Indians. HLA-DR4 was decreased in the RA group (n = 32) compared with controls (n = 62) (6% vs 21% p = 0.07). The predominant DR4 allele observed was DRB1*0403 (Dw13.1). The most striking observation in these studies was a marked predominance of the DRB1*1402 allele encoding Dw16 (DRw14). This allele was present in 91% of RA cases, but was also highly prevalent in controls (80%, OR = 2.4 p = 0.20). DRB1*1402 only was observed in 47% of cases and 31% of controls. The DRB3*0101 (DRw52), and the DQA*0501 and DQB*0301 alleles encoding a subset of DQw3 were associated with DRB1*1402 in cases and in controls. HLA-Bw62 was increased in RA cases (28%) compared with controls (8%) (OR = 4.5, p = 0.01, corrected p = ns).

Adult↗

Variability of alpha-tocopherol values associated with procurement, storage, and freezing of equine serum and plasma samples.

Recent evidence concerning the pathogenesis of equine degenerative myeloencephalopathy indicated that low blood alpha-tocopherol values are a factor in the disease process. Variables that could be introduced by a veterinarian procuring, transporting, or storing samples were evaluated for effects on alpha-tocopherol concentration in equine blood. These variables included temperature; light; exposure to the rubber stopper of the evacuated blood collection tube; hemolysis; duration of freezing time, with and without nitrogen blanketing; and repeated freeze/thaw cycles. It was found that hemolysis caused the greatest change in high-performance liquid chromatography-measured serum alpha-tocopherol values, with mean decrease of 33% (P < 0.001). Lesser, but significant (P < 0.01) changes in serum alpha-tocopherol values were an approximate 10% decrease when refrigerated blood was left in contact with the red rubber stopper of the blood collection tube for 72 hours and an approximate 5% increase when blood was stored at 20 to 25 C (room temperature) for 72 hours. Repeated freeze/thaw cycles resulted in a significant (P < 0.05) 3% decrease in alpha-tocopherol values in heparinized plasma by the third thawing cycle. Freezer storage for a 3-month period without nitrogen blanketing resulted in slight (2%) decrease in mean serum alpha-tocopherol values, whereas values in serum stored for an identical period under nitrogen blanketing did not change. A significant (P < 0.001) mean decrease (10.3%) in alpha-tocopherol values was associated with freezer (-16 C) storage of nitrogen blanketed serum for 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Dw14(DRB1*0404) is a Dw4-dependent risk factor for rheumatoid arthritis. Rethinking the "shared epitope" hypothesis.

HLA-DR4 has been shown to be associated with risk for developing rheumatoid arthritis (RA) in multiple populations and racial groups. The allelic variants of DR4 share the DR4 serologic specificity but differ by 1 to 3 amino acids in the third hypervariable region (positions 67 to 74) and at positions 57 and 86 of the DR beta 1 chain. We have examined DR4 variants in 61 DR4+ RA cases and 55 DR4+ healthy controls. Dw14 was not associated with RA risk in DR4 heterozygous (DR4,X) cases. Only 15% of DR4,X cases had the Dw14 allele compared with 28% of DR4,X controls. In homozygous (DR4,4) individuals who also expressed Dw4, however, Dw14 was associated with increased RA risk. Moreover, the relative risk for Dw4,Dw14 (16.1, p = 0.001) actually exceeded that of Dw4,Dw4 (2.2, p = ns). Thus Dw14 is not an independent risk factor for RA but is a synergistic risk factor for individuals who also have the Dw4 allele.

Alleles↗

Variations of serum vitamin E, cholesterol, and total serum lipid concentrations in horses during a 72-hour period.

Fluctuations of serum vitamin E (alpha-tocopherol), cholesterol, and total lipids were monitored in 12 horses at 3-hour intervals for 72 hours. Mean coefficients of variation were 12, 5, and 15%, respectively. Statistical analyses were used to conclude that instrumentation error was accountable for only a small portion of the vitamin E variation. Results indicated that a single serum sample assay is an unsatisfactory indicator of vitamin E status in horses. These data have clinical application in the evaluation of horses suspected to be affected with equine degenerative myeloencephalopathy. The large variance of serum total lipids and the lack of correlation of it with serum vitamin E over time preclude the use of vitamin E/serum total lipids ratio in assessing vitamin E status.

Animals↗

Internal fixation versus hemiarthroplasty for the displaced subcapital fracture of the femur. A prospective randomised study.

A prospective randomised trial of surgical treatment for the displaced subcapital femoral fracture in patients of 70 years or more is presented. Two hundred and eighteen patients were randomly allocated into one of three treatment groups: manipulative reduction and internal fixation using Garden screws; Thompson hemiarthroplasty through a posterior (Moore) approach; and Thompson hemiarthroplasty through an anterolateral (McKee) approach. There is no significant difference in the mortality of the internal fixation and posterior arthroplasty groups. Both groups showed a significantly higher mortality than patients operated on through the anterior approach. The technical results of operation were worse in the internally fixed group, with only 40 per cent being satisfactory. Mobilisation was best achieved after the posterior approach. It is concluded that Thompson hemiarthroplasty, using an anterolateral approach, is the safest operation in this group of patients.

Aged↗

Single-blind study of diflunisal versus mefenamic acid in the treatment of pain after Colles' fracture.

A single-blind study was carried out in 52 patients with severe pain after Colles' fracture to assess the analgesic efficacy and tolerability of 500 mg diflunisal twice daily compared with that of 500 mg mefenamic acid given 3-times daily over a period of 5 days. The results showed that both treatments were effective in relieving pain, night pain and limitation of movement by pain, and there was no significant difference between the response in the two groups. Both drugs were tolerated and only 3 patients (2 on diflunisal) reported mild drug-related side-effects.

Adult↗