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Biomedical subjects

R J Powell

Publications and source records attributed to R J Powell.

At least 127 records · Page 7Linked to original sources
PubMed1994

Urine neopterin: a new parameter for serial monitoring of disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the role of serial measurement of urine neopterin concentration in monitoring the progression of systemic lupus erythematosus (SLE) disease activity scored using the British Isles Lupus Assessment Group (BILAG) index. METHODS: We followed prospectively 68 unselected SLE patients for a total of 464 patient months during which 233 separate assessments were carried out. At each assessment, urine neopterin, determined by high performance liquid chromatography, together with erythrocyte sedimentation rate (ESR) and plasma C3, C4, and C3d were measured and the SLE disease activity scored by a single observer. Serial data sets were analysed using time series modelling techniques. RESULTS: Single time point analysis showed a significant increase in urine neopterin concentrations in 14 patients who suffered flares of their disease during the study period (p = 0.02). Thirty patients with active disease went into disease remission with significant decreases in their urine neopterin values (p = 0.02). In the time series analysis, a statistically significant association was found between serial concentrations of urine neopterin and BILAG score (r = 0.6, p < 0.05); no other study parameter (ESR and serum C3, C4, and C3d) mirrored SLE disease activity as effectively. CONCLUSIONS: This study provides initial evidence that changes in urine concentrations of neopterin are significantly correlated with fluctuations in disease activity over time, scored using the BILAG index, amongst individual patients with SLE. Consequently, serial urine neopterin measurements appear to be clinically useful for monitoring disease activity and may contribute substantially to therapeutic decision making in these patients.

Adult↗
PubMed1994

Clinical experience with thalidomide in the management of severe oral and genital ulceration in conditions such as Behçet's disease: use of neurophysiological studies to detect thalidomide neuropathy.

OBJECTIVE: To examine the efficacy, dose, and safety profile, including neurophysiological testing of thalidomide used in 59 patients (including 23 with Behçet's disease) to treat severe oral or genital ulceration (OGU). METHODS: We identified prospectively subjects (including women of childbearing potential) who had persistent OGU over periods lasting one to 40 years and whose active ulceration was not controlled by other therapies. They were treated with thalidomide. Retrospectively, we identified the number of subjects with complete resolution of the ulcers at one and two months of thalidomide therapy, and the dose required to maintain that improvement in those individuals who relapsed after stopping thalidomide. The decrease from the baseline sensory nerve action potential (baseline SNAP) amplitude value (derived from median, radial and sural nerve SNAPs) at which the development of paraesthesiae was likely to occur was also determined. RESULTS: Complete resolution of the ulcers occurred in 81% of patients within one month of thalidomide therapy at doses of 200 mg/day. No further thalidomide was required by 20% of patients responding and in the remainder improvement was maintained with smaller doses (7-200 mg/day). Using an approximate 50% decrease from baseline SNAP as an indication to discontinue thalidomide, the incidence of symptomatic neuropathy was 13.5%. No patients with a decrease of less than 42% developed neuropathy, and a further 13.5% were asymptomatic with a decrease in SNAP between 42 and 69%. Other side effects were seen in 44% of patients. There were no pregnancies and no requirement for urgent pregnancy testing. CONCLUSIONS: Thalidomide provided a useful therapeutic option in severe oral and genital ulceration which had not responded to other therapies. The physician must remain vigilant to the continuing danger of axonal neuropathy and teratogenesis at all times during thalidomide therapy.

Adolescent↗
PubMed1994

Muscle biopsy abnormalities in systemic lupus erythematosus: correlation with clinical and laboratory parameters.

OBJECTIVES: To investigate the incidence and significance of Type II fibre atrophy, vessel wall thickening, lymphocytic vasculitis and myositis in needle quadriceps muscle biopsies from patients with systemic lupus erythematosus (SLE) and their correlations with clinical and laboratory parameters. METHODS: Needle quadriceps muscle biopsies from 55 patients with SLE and 26 controls were prospectively examined. Clinical and laboratory parameters recorded at the time of muscle biopsy included arthralgia, arthritis, myalgia, proximal weakness, vasculitic rashes, Schirmer test, ENA antibodies, ESR, serum creatine kinase (CK) and plasma C3 degradation products. RESULTS: Abnormal muscle biopsies were significantly more frequent in patients with SLE compared with controls (P < 0.005). None of the controls had lymphocytic vasculitis and/or myositis. The difference in incidence between patients with SLE and controls for lymphocytic vasculitis was significant at P < 0.005. Due to the small number of SLE patients with myositis, the difference in incidence for this abnormal finding reached only P = 0.09. In the SLE patient group, lymphocytic vasculitis was associated with significantly higher ESR values (P = 0.007) and higher incidence of arthritis (P = 0.01); and appears to characterise a subset of patients with positive Schirmer tests, anti-Ro and/or anti-La antibodies. Raised serum CK was found to correspond with underlying myositis in patients with SLE and these patients also had an increased incidence of symptoms of proximal weakness and/or anti-RNP antibodies. In contrast, both Type II fibre atrophy and vessel wall thickening failed to correlate with any of the clinical and laboratory parameters studied and appear to be non-specific findings. CONCLUSIONS: Abnormal muscle biopsies are common in patients with SLE and the presence of lymphocytic vasculitis and/or myositis signify pathology in these patients. Histopathological abnormalities in needle quadriceps muscle biopsies are further valuable parameters in the assessment of patients with SLE.

Adult↗
PubMed1994

Complement activation by cellulosic dialysis membranes.

AIMS: To assess the effect of cellulosic dialysis membranes on the production of complement degradation products to determine to the role of the classical pathway. METHOD: Complement activation was studied in 33 patients during a single haemodialysis session using cellulosic membranes. Pre- and post-dialysis plasma EDTA valves of C3, C4, C3dg, C4d and C reactive protein (CRP) were measured. Statistical analysis was done using the Wilcoxon signed rank test. RESULTS: Post-dialysis C4 (p = 0.0003), C3dg (p < 0.0001), and C4d (p = 0.003) concentrations were increased compared with pre-dialysis values. There was no significant change in C3 (p = 0.095) and CRP (p = 0.13) values. Post-dialysis C3dg and C4d concentrations correlated significantly (p = 0.007). IgG, an undialysed molecule, was quantified and post-dialysis valves were significantly higher than those before dialysis (p = 0.0002), indicating a degree of haemoconcentration. To remove this effect, the C3:IgG, C4:IgG, C3dg:IgG, C4d:IgG and CRP:IgG ratios were calculated. Compared with pre-dialysis values, post-dialysis C3dg:IgG and C4d:IgG ratios were increased and C3:IgG decreased significantly. No change was observed in C4:IgG and CRP:IgG ratios. CONCLUSION: This study confirms that significant complement activation takes place following dialysis with cellulosic membranes. This is denoted by an increase in C3dg. This was paralleled by a rise in C4d, implying a contributory role for the classical pathway. Concomitant post-dialysis increases in IgG and C4 indicate a degree of haemoconcentration; but removal of this effect shows that C3dg and C4d are increased following dialysis--suggesting classical, in addition to alternative, pathway activation.

Adult↗
PubMed1994

C3 nephritic factor and SLE: report of four cases and review of the literature.

We present four patients with C3 nephritic factor associated with partial lipodystrophy and/or mesangiocapillary glomerulonephritis type II. Each of these patients subsequently developed features of SLE, with an onset between 2 and 24 years after the development of the lipodystrophy or glomerulonephritis. All four patients had antinuclear antibodies and three of the four had anti-Ro antibodies. These patients bring to six the number of reported cases of this association. Possible explanations for the link between these two conditions are discussed.

Adult↗
PubMed1993

Mammalian polypeptide chain release factor and tryptophanyl-tRNA synthetase are distinct proteins.

A very high (approximately 90%) structural similarity exists between the bovine, human and murine tryptophanyl-tRNA synthetases (WRS), and quite unexpectedly the rabbit polypeptide chain release factor (eRF). This similarity may point to a very close resemblance or identity between these proteins involved in distinct steps of protein synthesis, or inadvertently to an incorrect assignment of the clone reported to encode eRF, since the structure of clones encoding WRS were confirmed by peptide sequencing. Using high resolution column chromatography and sucrose gradient centrifugation combined with assays for WRS and eRF activities, we show that functionally distinct WRS and eRF proteins can be completely separated from each other. Moreover, a putative anti-eRF monoclonal antibody appears incapable of immunoprecipitating the eRF activity or binding to protein(s) possessing eRF activity. This antibody binds to protein fractions which coincide in various separation procedures with rabbit WRS activity, and to pure bovine WRS. The protein expressed in Escherichia coli from the original cDNA clone initially reported to encode eRF, has WRS activity but not eRF activity. Resequencing of the fragment of the original rabbit cDNA demonstrates the presence of the previously overlooked HXGH motif typical of class I aminoacyl-tRNA synthetases. Consequently, mammalian WRS and eRF are different proteins, and the cDNA clone formerly assigned as encoding eRF encodes rabbit WRS.

Adenosine Triphosphate↗
PubMed1993

The prevalence and incidence of systemic lupus erythematosus in Nottingham, UK, 1989-1990.

The incidence and prevalence of systemic lupus erythematosus (SLE) in a well defined area in the Midlands was determined, by case ascertainment using multiple sources, during the period 1.5.89 to 30.4.90. This first such study of SLE in the UK showed incidence rates of 1.5/100,000/year for males and 6.5/100,000/year for females. The highest incidence was seen in age groups 40-49 and 50-59 years, with rates for females of 10.5 and 18.4/100,000/year respectively. Prevalence rates were 3.7/100,000/year for males and 45.4/100,000/year for females: SLE was found to be more prevalent amongst Afro-Caribbean groups. The socioeconomic status of the SLE patients was similar to the local study population, using social class by occupation and disadvantage by geographical area as indicators. Marked overlap between different sources of retrieval suggests that ascertainment of cases was high.

Adolescent↗
PubMed1993

Inclusion body myositis: an underdiagnosed condition?

Inclusion body myositis is an increasingly recognised form of inflammatory myopathy with characteristic clinical and histopathological features which has seldom been reported in the United Kingdom. This paper presents the clinicopathological features of a series of patients diagnosed in Nottingham from 1986 to 1990. During this period, 1319 muscle biopsy samples were processed by this laboratory and rimmed vacuoles were seen in 17 patients. Eleven patients had definite or probable inclusion body myositis according to published criteria. The mean age of the group was 69.4 years with a male to female ratio of 8:3. Typical clinical features were a slowly progressive painless, proximal lower limb weakness, with muscle wasting and early loss of reflexes. The median duration of illness from first symptom to presentation was five years (range 2-18 years). Falls were a prominent symptom in six patients and distal weakness occurred in nine patients. Creatine kinase was increased in 10 patients but only one had a level > 1000 IU/l; the erythrocyte sedimentation rate was normal in five patients. Treatment with steroids or cytotoxic drugs, or both, did not prevent disease progression. It is confirmed that inclusion body myositis is a distinct cause of inflammatory myopathy which is probably underdiagnosed in the United Kingdom. Clinically, it should be suspected in older patients presenting with muscle weakness of insidious onset. Pathologically, a careful search should be made for rimmed vacuoles and inflammation; ultrastructurally, the presence of inclusions will confirm the diagnosis.

Aged↗
PubMed1993

Prevalence of rheumatoid arthritis and rheumatoid factor in women: evidence for a secular decline.

OBJECTIVE: To determine the current prevalence of rheumatoid arthritis (RA) and rheumatoid factor positivity in the United Kingdom middle aged female population and to compare this with previous estimates to assess whether the disease is becoming less prevalent. METHODS: A cross sectional prevalence study was undertaken. All women aged 45-64 from the age and sex register of a large 11,000 general practitioner group practice in Chingford, East London were contacted and responders examined clinically and radiographically for the presence of RA by a single observer. Blood was also taken for rheumatoid factor testing (sheep cell agglutination test (SCAT), latex, and IgG). The prevalence in non-attenders was assessed from general practitioner and local hospital records. A diagnosis of definite or classical RA according to 1958 American Rheumatism Association criteria was used, and seropositivity was defined by a SCAT rheumatoid factor of 1/32 or more. RESULTS: From the 1003 women examined (response rate of 78.8%), 12 women had definite RA (1.2%, 95% confidence interval 0.6 to 1.8). Of these, 7/12 had definite erosive changes on radiography and 3/12 had a positive SCAT (> 1/32). Three cases of RA were also found in the 284 non-responders (prevalence 1.1%) by case-finding techniques. The rate of SCAT positivity in the whole study group was 0.5%. The rates of RA and SCAT positivity currently found in this group were less than those obtained in previous surveys. In the only previous large scale United Kingdom survey, performed in the north of England between 1958 and 1960, 406 women aged 45-64 were examined and 10 cases of definite RA were found, a prevalence of 2.5%. In the patients with RA 68% had erosions and 63% positive SCAT. The population SCAT positive rate in this and other surveys sampled between 1954 and 1961 was in the range of 4-5%, since when there has been a progressive decline according to a number of other studies. CONCLUSIONS: The prevalence of RA and rheumatoid factor in middle aged women is lower than previously believed and supports a variety of other data which indicate that RA is declining in incidence and severity.

Agglutination Tests↗
PubMed1993

Urine neopterin as a parameter of disease activity in patients with systemic lupus erythematosus: comparisons with serum sIL-2R and antibodies to dsDNA, erythrocyte sedimentation rate, and plasma C3, C4, and C3 degradation products.

OBJECTIVES--To investigate urine neopterin as a parameter of disease activity in an unselected group of patients with systemic lupus erythematosus (SLE) and to study the relation between urine neopterin and certain patterns of organ disease and differing drug regimens in the treatment of SLE. METHODS--Neopterin was determined by high performance liquid chromatography in 115 early morning urine samples from 68 patients with SLE. Serum soluble interleukin 2 receptor (sIL-2R) and antibodies to double stranded DNA (dsDNA) were determined by enzyme linked immunosorbent assay (ELISA), and the erythrocyte sedimentation rate (ESR), plasma C3, C4, and C3 degradation products (C3dg) were measured in corresponding blood samples. Disease activity was scored using the British Isles Lupus Assessment Group (BILAG) index. RESULTS--Urine neopterin was significantly increased in patients with active and inactive SLE compared with the control group and was significantly higher in patients with active than in those with inactive SLE. Urine neopterin did not distinguish between subsets of patients with SLE with particular patterns of organ disease, as defined by the BILAG index, nor was its level primarily influenced by differing drug regimens. Levels of serum sIL-2R, antibodies to dsDNA, the ESR, and plasma C3, C4, and C3dg were also significantly different between the patients with active and inactive SLE. Unlike urine neopterin there was considerable overlap in the values of these parameters between the two activity groups. Highly significant correlations found between urine neopterin and serum sIL-2R, ESR, and plasma C3, C4, and C3dg suggest the close association of neopterin with clinical activity in SLE. Multivariate logistic regression analysis showed that urine neopterin > 300 mumol/mol creatinine was a highly significant predictor of disease activity with an odds ratio of 3.51. CONCLUSIONS--Determination of urine neopterin, a non-invasive, relatively simple and inexpensive measurement, appears to be the best parameter for assessing and monitoring disease activity and treatment in patients with SLE.

Adult↗
PubMed1993

Distribution of cell adhesion molecules in skeletal muscle from patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the pathophysiology of perivascular mononuclear cell infiltrates observed in skeletal muscle from patients with systemic lupus erythematosus (SLE). METHODS: Immunocytochemical techniques were used to examine frozen 5 microns sections from the quadriceps needle muscle biopsy specimens of 14 patients with SLE (including seven with infiltrates) for the expression of the cytokine inducible adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. RESULTS: Vessels in 6/7 SLE biopsy specimens with perivascular infiltrates expressed VCAM-1 at a density of > 2 vessels/mm2 in contrast with 0/7 SLE biopsy specimens without infiltrates and 1/6 control specimens. In contrast, E-selectin expression was increased ( > 0.3 positive vessels/mm2) in SLE biopsy specimens compared with control tissue regardless of the presence of perivascular infiltration. VCAM-1 and ICAM-1 were also noted on extravascular cells in the infiltrates, being particularly prominent on the intermuscle fibre dendritic processes of CD68+ HLA-DR+ cells. CONCLUSION: Expression of these cytokine inducible adhesion molecules may be important in the migration of mononuclear cells into skeletal muscle and may be involved in intercellular interactions within the tissue.

Adult↗
PubMed1993

Focal myositis: an unusual cause of bilateral upper eyelid swellings.

Focal myositis is considered a rare self-limiting inflammatory swelling of skeletal muscle. Focal involvement of individual muscle or muscle groups with severe myopathic and inflammatory changes characterizes the histology. We report the development of progressive focal myositis in both upper eyelids of a 34 year old man that responded to immunosuppressive therapy.

Adult↗
PubMed1993

Decreased red blood cell deformability and impaired oxygen utilization during human sepsis.

Sepsis is characterized by decreased microcirculatory flow and increased peripheral shunting. Previous studies have shown red blood cell deformability (RCD) is decreased during sepsis. The purpose of this study was to evaluate the effect of changes in RCD on hemodynamics and oxygen utilization during sepsis. RCD, arteriovenous oxygen difference (DA-VO2), mixed venous oxygen saturation (MVO2), intrapulmonary shunt (QS/QT), cardiac index, and systemic vascular resistance were measured in 10 trauma patients, all of whom had or developed clinical sepsis. Data are expressed as mean +/- SD. Patients with normal RCD (> 0.75) were compared with those with low RCD (< 0.75). Patients with low RCD had a significantly higher incidence of sepsis (100% vs. 20%, P < 0.05, Student's t test or Fisher's Exact Test), lower DA-VO2 (2.4 +/- 0.9 vs. 4.8 +/- 1.5 P < 0.05, Student's t test or Fisher's Exact Test), and higher MVO2 (79 +/- 8 vs. 65 +/- 11 P < 0.05, Student's t test) or Fisher's Exact Test) than those patients with normal RCD. There was a direct correlation between RCD and DA-VO2 (r = 0.852, P < 0.001). MVO2 correlated inversely with changes in RCD (r = 0.813, P < 0.001). No significant correlation existed between RCD and cardiac index or systemic vascular resistance. Patients with low RCD demonstrated impaired oxygen utilization; changes in RCD correlated closely with changes in DA-VO2 and MVO2. These data suggest that decreased RCD may have an etiologic role in the impaired oxygen utilization that occurs during sepsis.

Bacterial Infections↗
PubMed1992

Autoantibodies in pet dogs owned by patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) occurs in human beings and in dogs. There is evidence to suggest that the disease is caused by a transmissible factor that may cross the species barrier. We investigated this possibility by looking for autoantibodies and serum protein abnormalities in serum samples from 15 pet dogs owned by patients with SLE and comparing results with those obtained with serum from 10 healthy dogs kept in a controlled environment and 9 dogs with autoimmune diseases. We used standard immunological assays modified for use with canine samples. Compared with the normal dogs, increased amounts of antibody to double-stranded DNA were found in serum from the SLE patients' dogs (median optical density [405 nm] = 0.117 vs 0.299; p = 0.0001), this latter amount being similar to that found in serum from the autoimmune group (0.201; p = 0.6). Abnormal serum protein electrophoresis patterns were found in samples from the autoimmune and SLE patients' dogs but not the normal dogs. These findings support the idea that exposure to common environmental factors or transmissible agents may have a role in causing SLE.

Animals↗