Outsourcing. Inside out, upside down.
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Contract Services↗
Biomedical subjects
R Thomas
Publications and source records attributed to R Thomas.
Elevated interleukin-10 levels in patients with rheumatoid arthritis.
OBJECTIVE: Interleukin-10 (IL-10) has been shown to exert both antiinflammatory and immunostimulatory effects in vivo and in vitro. We therefore sought to examine the role of this cytokine in rheumatoid arthritis (RA) by assessing serum and synovial fluid IL-10 levels. METHODS: Serum and synovial fluid samples were collected from patients with RA and patients with various inflammatory, infectious, and noninflammatory arthritides (controls). IL-10 was assayed using an IL-10-specific enzyme-linked immunosorbent assay, and messenger RNA (mRNA) levels were assessed by semi-quantitative polymerase chain reaction (PCR) techniques. RESULTS: Both RA serum and synovial fluid contained significantly elevated IL-10 levels compared with levels in normal subjects or in control patients (P < 0.01). Some patients with spondylarthropathy also manifested increased serum levels of IL-10. Serum levels of IL-10 did not correlate with standard measures of clinical activity, but were shown to correlate significantly with serum rheumatoid factor (RF) titers and in vitro levels of spontaneous IgM-RF production (P < 0.05). PCR analyses demonstrated the constitutive expression of IL-10 mRNA by the non-T cell population, and semiquantitative PCR analysis documented elevated levels of IL-10 mRNA in circulating mononuclear cells of those RA patients who were not treated with slow-acting antirheumatic drugs. Analysis of IL-10 mRNA revealed the cytokine to be of human, and not viral, origin. CONCLUSION: These data suggest that there is increased production of IL-10 by non-T cells in patients with RA. This may contribute to the diminished T cell function and increased antibody and RF production in these patients.
Adult↗
CD80 expression in rheumatoid arthritis: comment on the article by Ranheim and Kipps.
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Arthritis, Rheumatoid↗
Leukocyte CD18 receptors may be a better target than ICAM-1 ligands for reducing histologic evidence of cellular and vascular rejection in the rabbit.
Building evidence suggests that blocking the ICAM-1/CD18 interaction may affect the course of graft rejection. Treatment with monoclonal antibody (mAb) to CD18 was compared to antibody to ICAM-1 in a rabbit heterotopic heart transplant model to determine whether blocking the leukocyte receptor for ICAM-1, CD18, was more effective than antibody targeting of the ligand for ICAM-1. Following transplantation, 28 recipient rabbits were randomized to receive either placebo, mAb to CD18, or mAb to ICAM-1 for 7 days until sacrifice. The cellular rejection grade and percentage of arteries with vascular rejection were significantly lower in animals treated with anti-CD18 than with anti-ICAM-1. As assessed by histology, antibody treatment was more effective in reducing both cellular and vascular rejection when directed at the leukocyte receptor CD18 than the ICAM-1 ligand. These findings suggest that other ICAM ligands may play an active role in the immune response and that CD18 may be important for migration of lymphocytes through myocardium.
Animals↗
Speech and language disorders in patients with high grade glioma and its influence on prognosis.
One hundred and sixteen patients with high grade glioma were entered into a prospective phase two study and treated with accelerated radiotherapy from 1988 to 1993. In this cohort of patients we analysed speech deficit as a subdivision of global functional status in terms of incidence, category and prognosis for survival. Forty three patients (37%) had a speech deficit at presentation. Eighty percent of these had a component of expressive dysphasia, associated with considerable degree of awareness and distress. The overall median survival was 9.5 months. On univariate analysis, median survival in patients with speech difficulties (6 months) was worse than patients with normal speech (10.5 months) (log rang p = 0.005). Multivariate analysis established independent significance from age, Karnofsky Performance Status (KPS), gender, histological grade, extent of surgery and seizures. This paper highlights the importance of assessing individual categories of functional disability which in patients with high grade glioma include mobility, cognitive function and communication. Each of these factors may seriously affect an individual's activities of daily living, hence quality of life and separate analysis has a number of clinical implications. Firstly, with over a third of patients suffering speech difficulties, adequate speech therapy facilities should be freely available to score the degree of deficit, devise coping strategies and institute communication therapy. Secondly, an understanding of prognostic factors aids the critical analysis of phase two studies and the design and stratification of future prospective trials which should include an analysis of speech deficit. Thirdly, separating individual patients into good and bad prognostic groups can assist strategic management decisions.
Adult↗
Dynamical behaviour of biological regulatory networks--I. Biological role of feedback loops and practical use of the concept of the loop-characteristic state.
In the field of biological regulation, models dictated by experimental work are usually complex networks comprising intertwined feedback loops. In this paper the biological roles of individual positive loops (multistationarity, differentiation) and negative loops (homeostasis, with or without oscillations, buffering of gene dosage effect) are discussed. The relationship between feedback loops and steady states is then clarified, and the problem: "How can one conveniently disentangle complex networks?" is then considered. Initiated long ago, logical descriptions have been generalized from various viewpoints; these developments are briefly discussed. The recent concept of the loop-characteristic state, defined as the logical state located at the level of the thresholds involved in the loop, together with its application, are then presented. Biological applications are also discussed.
Arginine↗
Dynamical behaviour of biological regulatory networks--II. Immunity control in bacteriophage lambda.
A number of bacterial and viral genes take part in the decision between lysis and lysogenization in temperate bacteriophages. In the lambda case, at least five viral genes (cI, cro, cII, N and cIII) and several bacterial genes are involved. Several attempts have been made to model this complex regulatory network. Our approach is based on a logical method described in the first paper of the series which formalizes the interactions between the elements of a regulatory network in terms of discrete variables, functions and parameters. In this paper two models are described and discussed, the first (two-variable model) focused on cI and cro interactions, the second (four-variable model) considering, in addition, genes cII and N. The treatment presented emphasizes the roles of positive and negative feedback loops and their interactions in the development of the phage. The role of the loops between cI and cro, and of cI on itself (which both have to be positive loops) was discovered earlier; this group's contribution to this aspect mainly deals with the possibility of treating these loops as parts of a more extended network. In contrast, the role of the negative loop of cro on itself had apparently remained unexplained. We realized that this loop buffers the expression of genes cro itself. cII, O and P against the inflation due to the rapid replication of the phage. More generally, negative auto-control of a gene appears an efficient way to render its expression insensitive (or less sensitive) to gene dosage, whereas a simple negative control would not provide this result.
Bacteria↗
Some developments in the biosynthesis of antibiotics.
In Prague in 1964, the participants in the International Congress on Antibiotics collectively presented an authoritative account of the existing understanding of the mechanism of biosynthesis of many of the major groups of antibiotics and other microbial metabolites. This information was derived to a large extent from applications of the then comparatively novel radioisotopic technique for studying the mode incorporation of labelled precursors. The intervening 30 years has witnessed remarkable progress in techniques for manipulating microbial genes and enzymes, while at the chemical level, advances in spectroscopic and chromatographic procedures have facilitated the use of stable isotopes as direct probes for the small scale exploration of metabolic pathways. As a consequence, our understanding of many mechanistic details has been considerably enhanced. Some of the developments to date will be reviewed, with particular reference to the elaboration of biosynthetic pathways leading to many of the antibiotics and other natural products described at the earlier Prague symposium.
Anti-Bacterial Agents↗
Femoral neuropathy following percutaneous nephrolithotomy of a pelvic kidney.
Management of nephrolithiasis within a pelvic kidney presents a novel challenge to the urologist. We report on a patient who underwent ureteral stent placement prior to extracorporeal shock-wave lithotripsy (ESWL). Following ESWL, the ureteral stent calcified at the vesical and renal ends, requiring "sandwich therapy" of percutaneous nephrolithotripsy, ESWL, and percutaneous nephroscopy. Percutaneous access to the pelvic kidney through a posterior approach was complicated by femoral neuropathy manifested by an ability to walk. With 6 months of aggressive physical therapy, the patient is now able to ambulate with difficulty using a walker.
Adult↗
Actinomycosis of the vallecula: report of a case and review of the literature.
A rare case of actinomycosis presenting primarily as a mass in the vallecula is described. The patient was a healthy, 65-year-old Saudi, lady who was not immunocompromised and had no other primary pathology in the oral cavity. The clinical presentation and management of the case are discussed and the relevant literature reviewed.
Actinomyces↗
Post intubation laryngeal sequelae in an intensive care unit.
The incidence, severity and pattern of post-intubation laryngotracheal sequelae in a 12 bed multidisciplinary intensive care unit (ICU) were assessed in this prospective study. One-hundred and fifty consecutive patients requiring intubation for more than 24 hours for various indications were studied. Evaluation of the larynx and trachea was done using a fibreoptic bronchoscope introduced through the endotracheal tube prior to elective extubation. Rigid bronchoscopy and direct laryngoscopy were performed in very small children and adults requiring tracheostomy. One-hundred and thirty-one (87.6 per cent) patients had visible laryngeal pathology in the immediate post-extubation period. Thirteen (8.6 per cent) had long term sequelae. A high incidence of long term sequelae was noted in patients with seizures (25 per cent) followed by patients with head injury (19 per cent). Steroid therapy failed to offer any significant protection but resulted in doubling of pulmonary sepsis. A grading system was adopted to classify acute laryngotracheal injury and a significant correlation was found between the presence of slough in the immediate post-extubation period and subsequent development of long term sequelae. There was also a significant correlation between a deeper insertion of the endotracheal tube and development subsequently of long term sequelae. The significance of these findings is discussed.
Adolescent↗
Decrease in circulating tryptophan availability to the brain after acute ethanol consumption by normal volunteers: implications for alcohol-induced aggressive behaviour and depression.
Acute ethanol consumption by fasting male volunteers decreases circulating trytophan (Trp) concentration and availability to the brain as determined by the ratio of (Trp) to the sum of its five competitors ([Trp]/[CAA]ratio). These effects of alcohol are specific to Trp, because levels of the 5 competitors are not increased. The decrease in circulating (Trp) is not associated with altered binding to albumin and may therefore be due to enhancement of hepatic Trp pyrrolase activity. It is suggested that, under these conditions brain serotonin synthesis is likely to be impaired and that, as a consequence, a possible strong depletion of brain serotonin in susceptible individuals may induce aggressive behaviour after alcohol consumption. The possible implications of these findings in the relationship between alcohol and depression are also briefly discussed.
Adult↗
Structural allografts for reconstruction of lower extremity open fractures with 10 centimeters or more of acute segmental defects.
Long-term results on the use of structural allografts (> or = 10 cm) to reconstruct large skeletal defects sustained during high-energy, open lower extremity fractures have not been reported. Eight patients are retrospectively reviewed at postallograft time periods ranging from 18 to 93 months. Two patients required reoperation for noninfectious causes, and each healed uneventfully. Four individuals developed infectious complications, but only one required complete allograft removal (amputation). The others remain infection free at follow-up. Using any of three different rating systems, excellent functional outcome results from this method of reconstruction in an otherwise exceptionally challenging extremity for limb salvage.
Adolescent↗
Information management and technology in England's large acute NHS hospitals. National strategy versus local reality.
Discusses the NHS Executive's information management and technology (IM&T) strategy and its relationship to the 1991 reforms. Examines the recommendation for large acute hospitals to adopt integrated hospital information support systems (HISS). Reports that a recent census of these hospitals, undertaken by the authors, suggests that the implementation of the strategy's recommendations has been slow at the local level. Attempts to diagnose the factors that are impeding implementation, using the evidence provided by the census. Identifies four main problem areas: the lack of success of past IM&T initiatives undermines confidence in the current strategy; the strategy is poorly aligned with other policy initiatives; the legacy of discrete, proprietary information systems within hospitals makes the creation of an integrative information environment difficult to accomplish without massive investment in new systems; and there are implicit contradictions between the following: the absence of a comprehensive post-implementation evaluation of the economic, technological and cultural feasibility of HISS at any of the three HISS pilot sites; the strategy's advocacy of HISS as the way forward for large acute hospitals; the requirement for a comprehensive business case to support any substantial investment in IM&T. Concludes that a massive rethink of policy is required, with a much greater emphasis on research, development and independent evaluation.
Confidentiality↗
Modifying the Barthel Performance Index Score for use in patients with brain tumours.
Performance status scores are useful tools in the management of patients with malignant disease. No specific performance index score exist, however, for patients with glioma. The Barthel Index, has been used in our department because it has been widely used in patients following stroke and found useful. This study aims to establish whether a modification of the Barthel Index would be more appropriate for patients with glioma and, if so, what modifications should be made. The opinions of multidisciplinary health workers and carers experienced in helping patients with glioma were established by questionnaire. Difficulty with speech and the presence of seizures were statistically ranked the most significant disability in terms of overall performance status. As these are not included in the Barthel Index a modification is justified. However, to include new categories in a performance index but avoid increasing its complexity, existing categories have to be omitted. Therefore, the second aim of this study was to establish which categories within the Barthel contribute least to a change in the total score. Three-hundred-and-thirty-three prospectively recorded Barthel scores were evaluated in 81 patients over 2 years and the individual categories evaluated by multifactor analysis. The sensitivity of the categories 'bowel function' and 'independence in grooming' to a change in the total score was less than 1%. In conclusion, substituting 'speech difficulties' and the presence of seizure in place of 'bowel function' and 'independence in grooming' from the Barthel Index will improve the specificity for patients with glioma without reducing the sensitivity or acceptability for the patients and research nurses who most often complete them.(ABSTRACT TRUNCATED AT 250 WORDS)
Activities of Daily Living↗
Molteno implant surgery for advanced glaucoma.
PURPOSE: The use of adjunctive antimitotics with conventional filtering surgery appears to have decreased the need for Molteno implants in glaucomas with a poor prognosis. We review the current status, results and complications of Molteno implants. METHODS: Review of the literature and practical experience from two university departments of ophthalmology. RESULTS: Improvements in the design and surgical techniques for Molteno implants have decreased the incidence of over filtration, but this and other complications continue to pose problems. Increased success rates may be possible if antimitotics are used with Molteno implants. CONCLUSION: Molteno implants continue to be an option when conventional filtration with or without antimitotics has failed; they continue to be regarded as a last resort for filtration. The use of antimitotics to increase the success rate of Molteno implants is not proven, but merits further investigation.
Conjunctiva↗
Reducing donor exposure in preterm infants requiring multiple blood transfusions.
Preterm infants frequently require multiple blood transfusions. Traditionally, 'fresh' (less than seven days old) blood has been used but this often results in transfusions from multiple donors. To reduce donor exposure the policy for top-up transfusions was changed. A unit of blood under five days old with additional satellite packs was ordered for each infant and used up to its expiry date, allowing up to eight transfusions from a single donation to be given. The mean (SD) number of transfusions per infant in 43 infants transfused according to previous policy and in 29 transfused according to the new policy was similar at 5.6 (4.0) and 5.3 (3.1), respectively. However, donor exposure fell following the change in policy from 4.9 (3.5) to only 2.0 (0.9). Only one infant was exposed to more than three donors compared with 24 infants in the control group. Plasma potassium concentrations were not significantly different following transfusion of blood stored for up to 33 days. This simple change in policy has reduced donor exposure in infants requiring multiple top-up transfusions.
Blood Donors↗
Left ventricular thrombi in a patient with the antiphospholipid syndrome.
A 41 year old woman with the antiphospholipid antibody syndrome presented with a cerebral embolus. This was caused by a mobile left ventricular thrombus that later resolved. There was an additional old left ventricular thrombus. Left ventricular thrombi such as these have not been previously described in this syndrome, and may have been under diagnosed.
Adult↗