Antiendothelial cell antibodies (AECA) in systemic lupus erythematosus (SLE).
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Animals↗
Biomedical subjects
G Hughes
Publications and source records attributed to G Hughes.
A structure-based model for the 16 kDa membrane sector of the vacuolar H(+)-ATPase.
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Amino Acid Sequence↗
Histiocytic necrotizing lymphadenitis, Kikuchi-Fujimoto's disease, associated with systemic lupus erythemotosus.
Histiocytic necrotizing lymphadenitis, Kikuchi-Fujimoto's Disease (KFD), is a condition rarely associated with systemic lupus erythematosus (SLE). The diagnosis of KFD can precede, postdate or coincide with the diagnosis of SLE. Lymphadenopathy is a common clinical presentation of KFD and SLE, and is histologically indistinguishable in both conditions. We describe two cases of KFD associated with SLE. The diagnosis of KFD in one case was made several years before the diagnosis of SLE, and the other was simultaneous. Both showed large lymphadenopathy, but neither fever nor neutropenia. Lymph-node biopsy showed necrosis, with proliferation of histiocytes and immunoblasts, paucity of neutrophils and absence of hemathoxilin bodies. Both patients responded favourably to steroid treatment. Patients with KFD should be assessed for SLE and have long-term follow-up checking for development of SLE. KFD should be ruled out in SLE flare-up accompanied by lymphadenopathy.
Adult↗
Budget management.
Budgetary responsibility gives you more control. Take time to master the fine detail, ask questions of your management and finance colleagues about anything you do not understand (you will not lose face), and develop the skills of lateral thinking and creative accountancy. Even if your budget is repeatedly overspent do not take it personally, ensure that management are aware of it and have a good night's sleep. Do not worry about it.
Accounting↗
Thromboprophylaxis with low molecular weight heparin (Fragmin) in high risk pregnancies.
Venous thromboembolic disease remains the commonest cause of maternal death. The management of thromboprophylaxis in high risk women during pregnancy is contentious. Low molecular weight heparins (LMW) have theoretical advantages compared with unfractionated heparin and warfarin but have been poorly studied in pregnancy. We report on the use of LMW heparin (Fragmin) as thromboprophylaxis in thirty four high risk pregnancies. All the women had a previous thrombosis or a thrombosis in their current pregnancy +/- a recognised thrombophilic state (eleven had the antiphospholipid syndrome). Fragmin was given subcutaneously to maintain trough anti-Xa activity of 0.15-0.2 U/ml and 2 h post injection levels of 0.4-0.6 U/ml. The levels were checked monthly during pregnancy. Most women required 5,000U Fragmin once daily during the first trimester unless they were greater than 100 kg at the start of pregnancy. The mean time for dosage increase was 20.5 week (S.D. 8.2). 26/34 pregnancies (76%) required 5,000 twice daily at the end of pregnancy. Epidural anaesthesia was managed by omitting Fragmin dose or inserting the needle 6 hours after the previous Fragmin injection. There were no thromboembolic events thrombocytopenias or excessive haemorrhage. One woman had osteoporotic vertebral collapse post partum, she had no other risk factors for osteoporosis. LWM heparin (Fragmin) appears to be efficacious in preventing recurrent thromboembolic disease in pregnant women at high risk, but it is notable that osteoporotic fractures occurred post partum in one woman. Further trials are required to determine optimal dosage and safety.
Adult↗
A phase I/II study of polymerized bovine hemoglobin in adult patients with sickle cell disease not in crisis at the time of study.
BACKGROUND: The painful episodes of sickle cell disease (SCD) involve vaso-occlusion and impaired oxygen delivery. HBOC-201, a hemoglobin-based oxygen carrier, has been shown to support oxygen delivery in animal studies and to be safe and well tolerated in normal human volunteers. Therefore, we speculated that it might have a therapeutic role in SCD. METHODS: Eighteen adults with SCD who were asymptomatic at the time of study were enrolled in a Phase I/II single-blind, placebo-controlled, dose-escalation study of HBOC-201. The primary purpose was to assess the safety of the material in this patient population. In addition, as a surrogate marker of efficacy, each subject underwent a variety of exercise tests before and after HBOC-201 was given. RESULTS: All HBOC-201 infusions were well tolerated by the study subjects and no evidence of toxicity was noted. In addition, there was a significant difference in heart rate response to the identical aerobic exercise workload when the study subjects who received HBOC-201 were compared to the subjects who received placebo (p = 0.0061). CONCLUSIONS: HBOC-201 was safely administered to patients with SCD who were not in crisis at the time of study. Furthermore, following infusion of the study material, subjects with SCD performed the identical aerobic exercise-induced workload with an increase in heart rate that was significantly less than the increase observed in the subjects who received an infusion of the saline placebo. These safety and surrogate efficacy data support the notion that HBOC-201 could have efficacy as a treatment for the vasoocclusive episodes of SCD.
Adult↗
AIDS and severe HIV disease: combined predictions for the United Kingdom to 1999.
The number of HIV infections prevalent in the United Kingdom (UK) at the end of 1994 have been estimated. Estimates of the future annual incidence and prevalence of AIDS and severe HIV disease have been calculated for the UK by combining recently published projections for Scotland with projections produced for England and Wales adjusted to account for Northern Ireland. The number of HIV infections prevalent in the UK at the end of 1994 was estimated to be about 23,000, 36% of them undiagnosed. It was estimated that 52% of prevalent infections were in homo/bisexual men, and 32% were in people exposed through heterosexual intercourse. Between 2100 and 2190 new cases of AIDS are expected to be reported in the UK each year from 1995 to 1999. It is predicted that a 30% rise in the number of cases exposed through heterosexual intercourse and a 17% rise in cases who inject drugs will be balanced by a 7% fall in cases among homo/bisexual men. Prevalent AIDS cases in the UK are expected to rise by 15%, from 3740 at the end of 1995 to 4290 at the end of 1999. The number of people expected to be living with severe HIV disease, including AIDS, will also rise by about 15%, from 7545 at the end of 1995 to 8650 at the end of 1999.
Acquired Immunodeficiency Syndrome↗
An investigation of the mechanism of inhibition of the Ca(2+)-ATPase by phospholamban.
The Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum has been reconstituted with peptides corresponding to the hydrophobic domain of phospholamban (PLB) with or without the three Cys residues replaced by Ala, and with PLB with the three Cys residues replaced by Ala [PLBcys-(1-52)]. Reconstitution with the hydrophobic domain of PLB[PLB(25-52)] was found to decrease the apparent affinity of the ATPase for Ca2+ with no effect on the maximal rate of ATP hydrolysis observed at saturating concentrations of Ca2+. Reconstitution with PLBCys-(1-52) decreased both the apparent affinity for Ca2+ and the maximal activity; the effect on maximal activity followed from a decrease in the rate of the Ca2+ transport step (E1PCa2-->E2P) as observed with the hydrophilic domain PLB(1-25). The concentration dependences of the effects of the hydrophobic domain and of the whole PLB molecule were very similar, suggesting that the hydrophilic domain made little contribution to the affinity of the ATPase for PLB. The effect of PLB on the ATPase was dependent on the molar ratio of phospholipid to ATPase, suggesting partition of the PLB between its binding site on the ATPase and the bulk lipid phase in the membrane. Neither PLB nor its hydrophobic domain affected the rates of phosphorylation or dephosphorylation of the ATPase. Despite their effects on the apparent affinity of the ATPase for Ca2+, neither PLB nor its hydrophobic domain had any effect on the true affinity of the ATPase for Ca2+, as measured from changes in the tryptophan fluorescence of the ATPase. The effects of PLB on the activity of the ATPase are the sum of the effects of its hydrophilic and hydrophobic domains.
Animals↗
Seroepidemiological survey of Taenia saginata cysticercosis in Kenya.
A sero-epidemiological study of Taenia saginata cysticercosis was carried out to determine the prevalence and distribution of the infection in three provinces of Kenya. Serum samples and meat inspection records were collected from cattle at slaughter at export and district abattoirs. Cattle origin and the presence of T. saginata cysticerci were noted as was the prevalence of other helminths such as Echinococcus granulosus and Fasciola gigantica. Serum samples were screened for circulating parasite antigen using a monoclonal antibody-based enzyme-linked immunosorbent assay (Ag-ELISA) and for ante-parasite antibody by indirect ELISA (Ab-ELISA). Eighty per cent of the sera were collected from cattle from the Rift Valley Province of Kenya. The prevalence of T. saginata cysticercosis and the other helminth infections varied between districts and was particularly high in Narok. Animal husbandry practices in arid areas such as Narok may be particularly conducive to transmission. The potential value of the Ag-ELISA for use in sero-epidemiological studies was verified by this study. It detected at least twice as many cases as T. saginata cysticercosis as meat inspection and, of the three methods investigated, was considered the most valuable.
Abattoirs↗
Interaction of dibutyltin-3-hydroxyflavone bromide with the 16 kDa proteolipid indicates the disposition of proton translocation sites of the vacuolar ATPase.
The organotin complex dibutyltin-3-hydroxyflavone bromide [Bu2Sn(of)Br] has been shown to bind to the 16 kDa proteolipid of Nephrops norvegicus, either in the form of the native protein or after heterologous expression in Saccharomyces and assembly into a hybrid vacuolar H(+)-ATPase. Titration of Bu2Sn(of)Br against the 16 kDa proteolipid results in a marked fluorescence enhancement, consistent with binding to a single affinity site on the protein. Vacuolar ATPase-dependent ATP hydrolysis was also inhibited by Bu2Sn(of)Br, with the inhibition constant correlating well with dissociation constants determined for binding of Bu2Sn(of)Br complex to the proteolipid. The fluorescence enhancement produced by interaction of probe with proteolipid can be back-titrated by dicyclohexylcarbodiimide (DCCD), which covalently modifies Glu140 on helix-4 of the polypeptide. Expression of a mutant proteolipid in which Glu140 was changed to a glycine resulted in assembly of a vacuolar ATPase which was inactive in proton pumping and which had reduced ATPase activity. Co-expression studies with this mutant and wild-type proteolipids suggest that proton pumping can only occur in a vacuolar ATPase containing exclusively wild-type proteolipid. The fluorescent enhancement of affinity of Bu2Sn(of)Br for the mutant proteolipid was not significantly altered, with the organotin complex having no effect on residual ATPase activity. Interaction of the probe with mutant proteolipid was unaffected by DCCD. These data suggest an overlap in the binding sites of organotin and DCCD, and have implications for the organization and structure of proton-translocating pathways in the facuolar H(+)-ATPase.
Adenosine Triphosphate↗
Are retroviruses involved in the aetiology of human breast cancer?
To further investigate the possibility for retroviral involvement in the etiology of human breast cancer we processed peripheral blood monocytes and malignant breast tissue biopsies from 10 patients with breast cancer (infiltrating ductal carcinoma or infiltrating lobular carcinoma; ages 40-80 years) and 20 normal healthy women (with no evidence or family history of breast cancer. 10 age-matched controls and 10 women age 22-27 years) for the assay of the retroviral enzyme, reverse transcriptase, using an ELISA and for election microscopy examination for the detection of retroviral-like particles. Reverse transcriptase activity was detected in 5 out of 10 samples of monocyte culture medium and in 1 out of 10 of malignant tissue biopsies from the patients with breast cancer. In contrast, reverse transcriptase was not detected in the culture medium of the monocytes from any of the control subjects. Electron microscopy did not reveal the presence of any retroviral-like particles in any sample of monocyte culture medium or in any of the malignant or normal breast tissue biopsies. Despite evidence for the presence of reverse transcriptase in a subsample of the monocyte culture medium and breast tissue biopsies from the cohort of breast cancer patients who participated in this study, the role of retroviruses in human breast cancer remains unclear.
Adult↗
Diagnosis of Taenia saginata cysticercosis in Kenyan cattle by antibody and antigen ELISA.
Sera from calves, either experimentally or naturally infected with Taenia saginata, were screened for an antibody response to T. saginata, and for parasite antigen, by enzyme-linked immunosorbent assays (ELISAs). An antibody response was detected by 3 weeks post infection (p.i.), rose to a peak at 10-12 weeks p.i., and was still in evidence 1 year p.i. Parasite antigen was first detected 4-7 weeks p.i. and persisted until the end of the experiment, over 1 year p.i. In the experimentally infected animals, cattle with 14 or more live cysticerci had detectable levels of parasite antigen in their sera at slaughter, while animals with live cyst burdens ranging from 0 to 4 were negative. Furthermore, levels of circulating antigen were positively correlated with live cysticercus burden in the experimental animals. In naturally infected cattle, 83% (5/6) of those with 30 or more live cysts, and 22% (5/23) of those with 1-29 live cysts, could be detected by the ELISA for parasite antigen, although no significant correlation between antigen level and live cyst burden could be detected. Antibody levels were not found to be associated with cyst burdens in either experimentally or naturally infected cattle. In slaughterhouse cattle, the antigen assay was almost three times as sensitive as meat inspection. However, there was no agreement between cattle found positive at meat inspection and those found positive by the antigen detection ELISA. One possible reason is that the ELISA only detects live cysts, while lesions left by dead cysts are more noticeable at meat inspection. The mouse monoclonal antibody-based antigen detection ELISA is of value for the diagnosis of naturally occurring, viable, T. saginata cysticercosis in live cattle and has an immediate application for field based epidemiological studies designed to determine prevalence.
Abattoirs↗
From proteins to proteomes: large scale protein identification by two-dimensional electrophoresis and amino acid analysis.
Separation and identification of proteins by two-dimensional (2-D) electrophoresis can be used for protein-based gene expression analysis. In this report single protein spots, from polyvinylidene difluoride blots of micropreparative E. coli 2-D gels, were rapidly and economically identified by matching their amino acid composition, estimated pI and molecular weight against all E. coli entries in the SWISS-PROT database. Thirty proteins from an E. coli 2-D map were analyzed and identities assigned. Three of the proteins were unknown. By protein sequencing analysis, 20 of the 27 proteins were correctly identified. Importantly, correct identifications showed unambiguous "correct" score patterns. While incorrect protein identifications also showed distinctive score patterns, indicating that protein must be identified by other means. These techniques allow large-scale screening of the protein complement of simple organisms, or tissues in normal and disease states. The computer program described here is accessible via the World Wide Web at URL address (http:@expasy.hcuge.ch/).
Amino Acids↗
Computerised tomography and acute traumatic head injury: time for change?
The aim was to reconsider the "Guidelines for initial management of head injury in adults"--particularly with respect to the indications for computerised tomographic (CT) scanning--suggested by "a group of neurosurgeons" over a decade ago and still followed in some accident and emergency (A&E) departments. These recommendations are placed in the context of more recent research and the increased number of A&E departments with on-site rapid access to a CT scanner but without a resident neurosurgical facility. A case can be made for an updated policy with more liberal indications for CT scanning of acutely head injured adults in peripheral A&E departments. However, calculating the cost-efficiency of more frequent use of what is now a common but relatively expensive resource would remain a challenge.
Acute Disease↗
Casualty: the BBC series--the role of the medical adviser.
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Humans↗
Negotiating skills.
The Collins English Dictionary defines negotiation as "a discussion set up or intended to produce a "settlement or agreement." It is a skill everyone uses on a regular basis in daily life; often without realising. A plan to meet friends fo an evening meal for example involves agreeing a time and venue--this is negotiation. As it is the the process of coming to terms with the "other side" and trying to get the best deal possible it is necessary to accept the fact that a conflict of interest does exist. There is an atmosphere of uncertainty until the deal is completed and one side may gain and one may lose relative to their opening position. For this skill to be successfully applied when working with clinical management colleagues, a formal set of guidelines is necessary. In this article I highlight some of the problems which can arise and offer a systematic approach to this difficult but rewarding management activity.
Humans↗
Committees--a personal view.
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Emergency Service, Hospital↗
Methaemoglobinaemia presenting with status epilepticus.
A case is reported of methaemoglobinaemia presenting with recurrent fits in the absence of cyanosis. A low oxygen saturation measured on pulse oximetry that fails to improve with oxygen treatment, the presence of "chocolate brown" blood that does not change on exposure to air, and a high PaO2 arterial blood gas with oxygen therapy should support such a diagnosis. A diagnostic blood methaemoglobin level should be obtained.
Adult↗