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Biomedical subjects

G R Hughes

Publications and source records attributed to G R Hughes.

At least 19 recordsLinked to original sources
PubMed2006

Atherogenesis in rheumatology.

Atherosclerosis is a chronic inflammatory disorder characterized by immune cell activation, inflammation driven plaque formation and subsequent destabilization. In other disorders of an inflammatory nature, the chronic inflammatory state per se has been linked to acceleration of the atherosclerotic process which is underlined by an increased incidence of cardiovascular disease (CVD) in disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphopholipid (Hughes) syndrome (APS). In addition to systemic inflammation, additional mechanisms have been put forward that are more specific for the pathophysiology of the individual chronic inflammatory disorders.

Annexin A5↗
PubMed2004

Microsatellite markers provide evidence for sexual reproduction of Mycosphaerella graminicola in Saskatchewan.

This study examined the genetic structure of a Saskatchewan population of Mycosphaerella graminicola, cause of the foliar disease Septoria tritici blotch of wheat. Such knowledge is valuable for understanding the evolutionary potential of this pathogen and for developing control strategies based on host resistance. Nine pairs of single-locus microsatellite primers were used to analyze the genomic DNA of 90 isolates of M. graminicola that were collected using a hierarchical sampling procedure from different locations, leaves, and lesions within a wheat field near Saskatoon. Allelic series at eight different loci were detected. The number of alleles per locus ranged from one to five with an average of three alleles per locus. Genetic diversity values ranged from 0.04 to 0.67. Partitioning the total genetic variability into within- and among-location components revealed that 88% of the genetic variability occurred within locations, i.e., within areas of 1 m(2), but relatively little variability occurred among locations. Low variability among locations and a high degree of variability within locations would result if the primary source of inoculum was airborne ascospores, which would be dispersed uniformly within the field. This finding was confirmed by gametic disequilibrium analysis and suggests that the sexual reproduction of M. graminicola occurs in Saskatchewan.

Alleles↗
PubMed2003

Current transport of leatherback sea turtles (Dermochelys coriacea) in the ocean.

While the long-distance movements of pelagic vertebrates are becoming known thanks to satellite telemetry, the factors determining their courses have hardly been investigated. We have analysed the effects of oceanographic factors on the post-nesting movements of three satellite-tracked leatherback turtles (Dermochelys coriacea) moving in the southwest Indian Ocean. By superimposing the turtle tracks on contemporaneous images of sea-surface temperatures and sea height anomalies, we show that currentrelated features dominate the shape of the reconstructed routes. After an initial offshore movement, turtles moved along straight routes when in the core of the current, or executed loops within eddies. Large parts of the routes were strikingly similar to those of surface drifters tracked in the same region. These findings document that long-lasting oceanic movements of marine turtles may be shaped by oceanic currents.

Animal Migration↗
PubMed2001

Systemic lupus erythematosus.

This review covers major advances in clinical issues related to systemic lupus erythematosus (SLE) published between 1995 and 2000. The classification criteria for both SLE and antiphospholipid syndrome (APS) have been updated, and up to 19 different subsets of neuropsychiatric lupus have been defined. New epidemiological data show that the incidence of new cases and the survival of patients with SLE are both increasing. Several randomised controlled trials have defined the role of cyclophosphamide, methotrexate, antimalarials, and hormonal treatment in the management of SLE. New data are available for drugs such as ciclosporin and thalidomide. Finally, several new treatments for severe refractory cases, such as mycophenolate mofetil and stem-cell transplantation, are being increasingly used. New data also refer to management of thrombosis in APS and high-risk pregnancies in women with SLE or APS.

Antiphospholipid Syndrome↗
PubMed2001

Hughes (antiphospholipid) syndrome. Clinical features.

Hughes (antiphospholipid) syndrome is a noninflammatory autoimmune disease. The most critical pathologic process is thrombosis, which results in most of the clinical features suffered by these patients. Recurrent thrombosis together with an adverse pregnancy history and the presence of antiphospholipid antibodies defines the syndrome.

Antibodies, Antiphospholipid↗
PubMed2001

Estrogen and progesterone receptors in murine models of systemic lupus erythematosus.

Estrogens are believed to play a role in the etiology of both human and murine systemic lupus erythematosus (lupus; SLE), presumably through the agency of their cellular receptor proteins. There is now considerable interest in the molecular mechanism of action of estrogens in immune tissues, particularly with regard to autoimmune disorders, which are generally more prevalent in women. In this laboratory, an attempt is being made to characterize estrogen receptors in murine models of SLE and to try and relate this to estrogen receptor function in vivo. The initial aim was to compare binding properties of estrogen receptors in brain, reproductive and immune tissues of BALB/c and MRL/MP-lpr/lpr mice. The latter strain spontaneously develops an autoimmune disease resembling human systemic lupus erythematosus (lupus; SLE). It is hypothesized that estradiol, through its receptors, mediates the progression of murine SLE, and that in autoimmune disease, the estrogen receptor is functionally and/or structurally changed. Initial studies suggest that there are differences in estrogen receptors between BALB/c mice, which do not get autoimmune disease, and two strains that do, MRL/MP-lpr/lpr and NZB/W mice. In MRL mice, these differences may be reflected in impaired priming of the progesterone receptor.

Animals↗
PubMed2001

Treatment of systemic lupus erythematosus.

The treatment of systemic lupus erythematosus (SLE) is mainly based on a number of "traditional" drugs such as corticosteroids, antimalarials, azathioprine and cyclophosphamide. However, this scenario is rapidly changing due to the introduction of new compounds. Some of these new agents have been successfully used in other diseases, while others are being specifically designed to interfere with the immune abnormalities seen in SLE. As our knowledge on the mechanisms of immune response increases, new drugs that can interfere with T and B cell interaction and activation, production of anti-dsDNA autoantibodies, immune-complexes deposition and cytokine activation have been developed and some of these are now under investigation in SLE. Although initial data regarding their safety and efficacy are encouraging, caution must be taken before these drugs are considered as the treatment of choice for specific SLE manifestations. Specifically, controlled clinical trials with sufficient number of patients are necessary. If the promising results already available are confirmed, the use of these drugs might represent the keystone in the future management of SLE and other autoimmune diseases.

Adjuvants, Immunologic↗
PubMed2001

Familial clustering of polymorphic light eruption in relatives of patients with lupus erythematosus: evidence of a shared pathogenesis.

BACKGROUND: Abnormal photosensitivity is a common feature of many forms of lupus erythematosus (LE). OBJECTIVES: To examine the role of polymorphic light eruption (PLE) as a possible predisposing factor for cutaneous forms of LE. METHODS: Eighty-five patients with well-characterized subacute cutaneous LE (SCLE) and discoid LE (DLE) were recruited from outpatient clinics, and the prevalence of PLE determined by detailed interview and clinical examination. RESULTS: Symptoms consistent with PLE were reported in 61% and 55% of SCLE and DLE patients, respectively; this was significantly higher than the overall population prevalence of 13.6% (P < 0.001), giving a relative risk (RR) for PLE in SCLE patients of 3.37 (95% confidence interval, CI 2.46--4.28) and DLE patients of 3.11 (95% CI 2.31--3.91). PLE developed before the onset of LE in 61% of cases (median interval 12 years, range 1--40), concomitantly in 24%, and subsequently in a further 15% (median interval 3.5 years, range 1--25). To delineate the relationship between PLE and LE further, the prevalence of PLE was determined in 103 otherwise unaffected first-degree relatives of SCLE and DLE probands; we had previously demonstrated clustering of PLE in families, reflecting a strong genetic component. We found a significantly higher PLE prevalence in relatives of the LE probands than in the general population (P < 0.001), giving an RR for PLE of 2.29 (95% CI 1.55--3.03) and 2.61 (95% CI 1.32--3.89) for female and male relatives, respectively. CONCLUSIONS: The high prevalence of PLE in LE patients, together with clustering of PLE among first-degree relatives of SCLE and DLE probands, suggests that there may be a shared pathogenetic basis for PLE and cutaneous LE. We propose that predisposition to PLE may contribute to the LE phenotype in otherwise susceptible individuals.

Confidence Intervals↗
PubMed2001

A candidate gene analysis of three related photosensitivity disorders: cutaneous lupus erythematosus, polymorphic light eruption and actinic prurigo.

BACKGROUND: Polymorphic light eruption (PLE) is a common inherited photosensitivity disorder, which may predispose to several related but distinct conditions, including subacute cutaneous lupus erythematosus (SCLE), discoid lupus erythematosus (DLE) and actinic prurigo (AP). OBJECTIVES: To examine specific candidate genes for shared susceptibility alleles between these related phenotypes. METHODS: Eighty-five caucasian patients with annular SCLE or DLE were recruited, in addition to 102 first-degree relatives. The prevalence of PLE in both the patient and relative groups was determined by detailed interview and clinical examination. Eighty-five patients with pure PLE and 59 patients with AP were also recruited. Candidate genes were analysed by typing of single nucleotide polymorphisms of IL10 (-1082 G/A and -819 C/T), FCGR2A (131 R/H), SELE (128 S/R), ICAM1 (241 G/R and 469 E/K), IL1A (+ 4845 G/T), IL1B (-511 C/T and + 3954 C/T), IL1RN (+ 2018 T/C) and TNF (-308 G/A) using polymerase chain reaction (PCR) with sequence-specific primers and 5'-nuclease PCR. RESULTS: A significant association was found between SCLE and the rare TNF -308 A allele when compared with patients with DLE (P = 0.043), PLE (P = 0.001), AP (P < 0.001) and healthy controls (P < 0.001). However, there was strong linkage disequilibrium between TNF -308 A and the HLA A*01, B*08, DRB1*0301 haplotype. A negative association was also found between SCLE and the IL1B + 3954 T allele (P = 0.039), but the significance was lost on correction for multiple testing. CONCLUSIONS: We have demonstrated the association of SCLE with the rare TNF -308 A allele, which may be pathogenic or, alternatively, a marker allele for the extended HLA A*01, B*08, DRB1*0301 haplotype that is associated with a number of autoimmune conditions. Although many of the other loci that we chose failed to demonstrate an association, a candidate gene approach remains the most logical one, and the most likely to yield positive results in the future.

Alleles↗
PubMed2001

HLA class II gene polymorphisms in antiphospholipid syndrome: haplotype analysis in 83 Caucasoid patients.

OBJECTIVES: We investigated the association between HLA class II haplotypes and antiphospholipid syndrome (APS). METHODS: HLA DRB1, DQB1 and DQA1 genotypes were determined by the polymerase chain reaction using sequence-specific primers in 83 Caucasoid British patients with APS. The genotype frequencies were compared between subgroups of patients and 177 healthy controls. RESULTS: DQB1*0604/5/6/7/9-DQA1*0102-DRB1*1302 and DQB1*0303-DQA1*0201-DRB1*0701 haplotypes showed significantly positive correlations with APS [P=0.0087 and P=0.0012, respectively]. The association of the former was enhanced in primary APS patients with anti-beta 2-glycoprotein I antibodies (anti-beta 2GPI) [odds ratio 6.2, 95% confidence interval (2.2-17.6), P=0.0014, corrected P=0.042]. CONCLUSIONS: These alleles and haplotypes might affect anti-ss2GPI production and APS development in different and heterogeneous fashion.

Adolescent↗
PubMed2001

Chromium-51 ethylenediamine tetraacetic acid glomerular filtration rate: a better predictor than glomerular filtration rate calculated by the Cockcroft-Gault formula for renal involvement in systemic lupus erythematosus patients.

OBJECTIVE: To investigate whether the ethylenediamine tetraacetic acid (EDTA) glomerular filtration rate (GFR) is a better indicator of the degree of renal involvement than serum creatinine concentration or creatinine clearance calculated by the Cockroft-Gault formula. METHODS: We studied prospectively all systemic lupus erythematosus (SLE) patients with normal or borderline serum creatinine concentration (<110 micromol/l) and urinary sediment abnormalities and/or proteinuria in the last 2 yr. EDTA-GFR, serum creatinine concentration, calculated creatinine clearance (Cockroft-Gault formula) and 24-h urine protein were determined at the same time. Renal biopsies were performed in patients with low values of EDTA-GFR or significant proteinuria. RESULTS: Twenty-three patients were identified, of whom 22 were females. The average age of the patients was 31.6+/-8.2 yr. Biopsies were assigned to WHO classes as follows: class II, 1 patient; class III, 6 patients; class IV, 10 patients; class V, 6 patients. The average serum creatinine concentration, EDTA-GFR and calculated creatinine clearance were 79.8+/-mol/l, 74.5 ml/min and 97 ml/min respectively. EDTA-GFR showed abnormal values (<80 ml/min) in 15 of the 23 patients (65.2%) while calculated creatinine clearance was abnormal (<80 ml/min) in three of the 23 patients (13%) (P<0.001). Using the Pearson correlation test, we did not find any correlation between EDTA-GFR or creatinine clearance values and the sum of activity and chronicity indices. CONCLUSION: GFR performed by EDTA-GFR correctly predicted renal involvement in SLE patients, whereas GFR calculated by the Cockcroft-Gault formula may have underestimated renal function. Significant numbers of patients with WHO class III, IV or V lupus nephritis may be missed if biochemical creatinine clearance or serum creatinine concentration alone is used to assess renal disease.

Adolescent↗
PubMed2001

Characteristics of patients with antiphospholipid syndrome with major bleeding after oral anticoagulant treatment.

OBJECTIVE: To study the demographic and clinical characteristics of patients with antiphospholipid syndrome (APS) with serious haemorrhagic complications of anticoagulant treatment in an attempt to establish risk factors for bleeding. METHODS: Patients with APS who were attending our lupus unit and who presented with severe bleeding while receiving oral anticoagulation were studied retrospectively. Severe bleeding was defined by the need for admission to hospital. Demographic data, clinical features, concomitant diseases and drugs, warfarin doses, duration of anticoagulation, and International Normalised Ratios (INR) at the time of bleeding were collected. RESULTS: Fifteen patients were included in the study (12 with systemic lupus erythematosus (SLE) plus APS and 3 with primary APS). The median age was 41.7 (range 27-66) and the median duration of the disease was 12.9 years (range 3-22). Duration of anticoagulation was between 10 days and 17 years. The INR at the time of bleeding was under 3 in 4 patients, between 3 and 4 in 5 patients and above 4 in 6 patients. There were 4 episodes of subdural haematoma, 4 episodes of renal haematoma (two after renal biopsy), 2 episodes of ovarian haemorrhage, 2 episodes of rectal haemorrhage, 1 episode of menorrhagia, 1 episode of haemarthrosis, and 1 episode of spinal haematoma. Concomitant drugs were aspirin in 9 patients, antibiotics in 2 patients, and azathioprine in 3 patients. In 6 patients hypertension was present as a concomitant disease. There were no deaths due to bleeding. Anticoagulant treatment was restarted in all patients and 3 of them had a new episode of bleeding. CONCLUSION: No relation was established between age, duration of oral anticoagulant treatment, and bleeding. Concomitant drugs, mainly aspirin, and high blood pressure were present at the time of bleeding in a large number of patients.

Adult↗
PubMed2001

Antiaggregant and anticoagulant therapy in systemic lupus erythematosus and Hughes' syndrome.

Antiaggregant and anticoagulant drugs are essential in the management of the manifestations due to antiphospholipid syndrome (APS) in patients with primary Hughes' syndrome or systemic lupus erythematosus. Coumadin derivatives (warfarin and acenocumarol), heparin and aspirin are used for secondary thromboprophylaxis and treatment of recurrent miscarriage. The available evidence for each indication is reviewed in this paper. There is still debate regarding the optimal intensity of oral anticoagulation, the best drug combination for pregnancy failure in APS and the management of asymptomatic patients with antiphospholipid antibodies.

Anticoagulants↗