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Biomedical subjects

D G Scott

Publications and source records attributed to D G Scott.

At least 37 records · Page 2Linked to original sources
PubMed1998

Churg-Strauss syndrome in a district hospital.

Published series on Churg-Strauss syndrome (CSS) come from tertiary referral centres. We retrospectively studied 23 patients with CSS (18 male) seen over 14 years (1982-1995) in a District General Hospital serving a population of 500,000. Mean age of onset of vasculitis was 57, 10-19 years older than in previous series. The commonest clinical features were asthma (22) and eosinophilia > 1.5 x 10(9)/l (21). Systemic vasculitis involving two or more extrapulmonary organs occurred in 22 patients, with specific organ involvement of nervous system (18), joints (13), muscles (13), lungs (11), skin (11), kidneys (11), heart (10), and bowel (7). Various classification systems were applied including the Lanham criteria, which were met in 19 patients; the American College of Rheumatology criteria, met in 14; Churg and Strauss criteria, met in four; and the Chapel Hill Consensus definition, met only in two. ANCA was detected in 10/17 patients where measured. Treatment included corticosteroids (21), cyclophosphamide (8), azathioprine (9), immunoglobulin (2), and methotrexate (1). During follow-up six patients died, two due to myocardial vasculitis (mean age 52 years), three due to infection (mean age 80 years), and one cause unknown. Significant long-term disability was due to asthma in five and neuropathy in six.

Adult↗
PubMed1998

Cutaneous vasculitis in a defined population--clinical and epidemiological associations.

OBJECTIVE: To examine the value of the American College of Rheumatology (ACR) 1990 criteria for Henoch-Schönlein purpura (HSP) and hypersensitivity vasculitis (HSV) and the Chapel Hill Consensus Conference (CHCC) definition of cutaneous leukocytoclastic angiitis (CLA) in the classification of cutaneous vasculitis and to estimate the annual incidence of biopsy proven cutaneous vasculitis in a well defined population. METHODS: ACR criteria for HSP and HSV and the CHCC definition for CLA and HSP were applied to an unselected cohort of 84 patients with biopsy proven cutaneous vasculitis attending a single district hospital in the United Kingdom between January 1990 and December 1994. RESULTS: Thirty-seven patients fulfilled ACR criteria for HSV, of whom 27 also fulfilled the ACR criteria for HSP. Thirty-two patients met the CHCC definition for CLA and 7 the CHCC definition for HSP. The overall annual incidence of cutaneous vasculitis was 38.6/million (95% CI 30.6-48.1), and for CLA 15.4/million (95% CI 10.6-21.8). CONCLUSION: The ACR 1990 criteria for HSP and HSV overlap; the CHCC definitions for CLA and HSP provide clearer distinction. Cutaneous vasculitis is as common as systemic vasculitis.

Antibodies, Antinuclear↗
PubMed1998

Safety and tolerability of conversion from stable Sandimmun maintenance treatment to Sandimmun Neoral in patients with rheumatoid arthritis.

OBJECTIVE: To assess the safety and tolerability of converting patients with rheumatoid arthritis (RA) taking a stable dose of cyclosporin A (CyA) maintenance treatment (Sandimmun, SIM) to a new microemulsion capsule formulation, Sandimmun Neoral (Neoral), at an initial dose of 2.5 mg/kg/day. METHODS: In this single arm, open multicenter study, 28 patients were recruited to enter a 6 week pre-conversion period; of these, 22 patients completed 12 weeks' treatment with Neoral. RESULTS: During the 12 week post-conversion period, 11 patients experienced adverse events considered to be drug related; most were mild to moderate in severity and reflected the known safety profile for CyA. Only slight differences in efficacy variables were observed after conversion. The mean Neoral dose at Week 12 (2.84 mg/kg/day) was lower than the mean SIM pre-conversion dose (3.38 mg/kg/day). The study showed that, in patients with RA undergoing stable SIM maintenance treatment, conversion to an initial Neoral dose of 2.5 mg/kg/day did not give rise to any clinically relevant safety and tolerability concerns, and efficacy of the treatment was maintained compared with SIM. CONCLUSION: This conversion strategy constitutes a clinically acceptable alternative to a 1:1 dose conversion.

Adult↗
PubMed1997

Blood transfusion, smoking, and obesity as risk factors for the development of rheumatoid arthritis: results from a primary care-based incident case-control study in Norfolk, England.

OBJECTIVE: To examine a range of demographic, social, and clinical risk factors for the development of rheumatoid arthritis (RA). METHODS: Population-based case-control study in Norfolk, England, involving adult patients, ages 18-70, with an inflammatory polyarthritis of <12 months' duration who were recruited from the Norfolk Arthritis Register. Controls, matched for sex and date of birth, were selected from the primary care register of the Norwich Health Authority. Both cases and controls completed identical self-administered questionnaires. Matched analysis of the 165 case-control sets was conducted for the whole group and for the subset in which the cases satisfied the 1987 American College of Rheumatology criteria for RA. RESULTS: The controls were of higher socioeconomic status than the cases. This was probably due to response bias. Having a body mass index > or =30 was associated with an adjusted odds ratio (OR) of 3.74 for developing RA (95% confidence interval [95% CI] 1.14-12.27). RA was also associated with a history of blood transfusion (OR 4.83, 95% CI 1.29-18.07). Even after correcting for social class, a history of having ever smoked was associated with a higher risk of developing RA (OR 1.66, 95% CI 0.95-3.06). There was no difference between cases and controls in previous exposure to childhood infections, certain surgical procedures, or reproductive history variables. CONCLUSION: RA has a number of potential environmental triggers, including smoking, obesity, and blood transfusion.

Adult↗
PubMed1997

Classification and epidemiology of the vasculitides.

The systemic vasculitides are rare inflammatory conditions of blood vessel walls. A number of different classification schemes have been published since the first in 1952. The important developments have been the recognition of dominant blood vessel size, the distinction between primary and secondary vasculitis and the incorporation of pathogenic markers such as anti-neutrophil cytoplasmic antibodies. In 1990 the American College of Rheumatology (ACR) published criteria for the diagnosis of polyarteritis nodosa, Churg-Strauss syndrome, Wegener's granulomatosis, hypersensitivity vasculitis, Schönlein-Henoch purpura, giant cell arteritis and Takayasu arteritis. Sensitivity and specificity rates varied considerably: 71.0-95.3% for sensitivity and 78.7-99.7% for specificity. The criteria were not tested against the general population or against patients with other connective tissue diseases or rheumatic conditions. Four years later the Chapel Hill Consensus Conference (CHCC) produced definitions for the major types of vasculitis, however, these have proved controversial. Comparison in unselected patients with systemic vasculitis (in particular polyarteritis nodosa and microscopic polyangiitis) has shown that the ACR criteria and CHCC definitions identify different patients. The systemic vasculitides are somewhat more common than previously believed. The overall annual incidence approaches 40/million adults. The most common form of primary systemic vasculitis is giant cell arteritis; Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome have similar incidences. Classical polyarteritis nodosa and Takayasu arteritis are very rare in the UK.

Humans↗
PubMed1997

Neoral--new cyclosporin for old?

Cyclosporin A is now well established as an effective second-line drug to treat rheumatoid arthritis. In April 1995, the microemulsion-based formulation of cyclosporin (Neoral) was introduced based on its increased bioavailability at 'no extra cost'. There may have been concerns that with increased bioavailability of Neoral, some patients might experience increased toxicity, particularly if transferring from Sandimmun to Neoral at the same dose. We describe our experience of 51 patients treated with Neoral--39 with rheumatoid arthritis, six with psoriatic arthritis and the remainder with a variety of diseases, including Behçet's, systemic lupus erythematosus and juvenile chronic arthritis. All patients continued their other medication including non-steroidal anti-inflammatory drugs and analgesics. Five continued low dose prednisolone (average 7.5 mg per day) all patients were monitored for safety and efficacy throughout their treatment according to standard protocol. Five patients were enrolled in a study of efficacy and safety where the dose of cyclosporin was reduced to 2.5 mg/kg/day at the time of conversion, i.e. to Neoral 2.5 mg/kg/day; 19 patients were converted dose for dose, cyclosporin A dose range 2.5-4 mg/kg/day converted to Neoral dose range 2.5-4 mg/kg/day and 27 patients started Neoral de novo. We conclude that cyclosporin is a useful disease modifying anti-rheumatic agent, and our experience suggests that the new formulation, Neoral, has a similar safety and efficacy profile to the original preparation (Sandimmun). Neoral was relatively easy to manage and we noted a slight reduction in dose when compared to Sandimmun. With dose adjustments over 18 months the mean dose for patients with RA fell from 3.2 to 2.7 mg/kg/day and of the 27 patients starting Neoral de novo only seven required an increased dose above 2.5 mg/kg/day in order to establish efficacy.

Adolescent↗
PubMed1997

Presence of psoriasis does not influence the presentation or short-term outcome of patients with early inflammatory polyarthritis.

OBJECTIVE: To determine whether the presence of psoriasis influences the presentation and early outcome of disease in a primary case based inception cohort of patients with early inflammatory polyarthritis. METHODS: In total, 966 patients with early inflammatory polyarthritis referred to the Norfolk Arthritis Register were studied. The clinical and demographic variables of patients with and without psoriasis were compared. RESULTS: Fifty-one patients (5.3%) had psoriasis on examination. Compared to other patients with inflammatory polyarthritis, those with psoriasis were significantly more likely to be male (49 vs 34%) and less likely to be seropositive for rheumatoid factor (RF) (13 vs 31%). The pattern of joint involvement was similar, as was the outcome at one year. Fewer patients with psoriasis developed radiological erosions (22 vs 39%). Multivariate analysis suggested that this was due to RF acting as a confounder. CONCLUSION: Among patients with early inflammatory polyarthritis there are few strong differences between patients with and without psoriasis, some of which may be accounted for by the absence of RF.

Adolescent↗
PubMed1997

Differences in the urinary metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in black and white smokers.

Incidence and mortality rates for lung cancer in the United States are significantly greater in blacks than in whites. This disparity cannot be explained by differences in smoking behavior. We hypothesize that the observed racial differences in risk may be due to differences in the metabolic activation or detoxification of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). To test this, different biomarkers of NNK exposure and metabolism, including the urinary metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and the presumed detoxification product [4-(methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-O-D-glucosiduronic acid (NNAL-Gluc), were examined along with questionnaire data on lifestyle habits and diet in a metabolic epidemiological study of 34 black and 27 white healthy smokers. Results demonstrated that urinary NNAL-Gluc:NNAL ratios, a likely indicator of NNAL glucuronidation and detoxification, were significantly greater in whites than in blacks (P < 0.02). In addition, two phenotypes were apparent by probit analysis representing poor (ratio < 6) and extensive (ratio > or = 6) glucuronidation groups. The proportion of blacks falling into the former, potentially high-risk group was significantly greater than that of whites (P < 0.05). The absolute levels of urinary NNAL, NNAL-Gluc, and cotinine were also greater in blacks than in whites when adjusted for the number of cigarettes smoked. None of the observed racial differences could be explained by dissimilarities in exposure or other sociodemographic or dietary factors. Also, it is unlikely that the dissimilarities are due to racial differences in preference for mentholated cigarettes, because chronic administration of menthol to NNK-treated rats did not result in either increases in urinary total NNAL or decreases in NNAL-Gluc:NNAL ratios. Altogether, these results suggest that racial differences in NNAL glucuronidation, a putative detoxification pathway for NNK, may explain in part the observed differences in cancer risk.

Adult↗
PubMed1996

Effect of classification on the incidence of polyarteritis nodosa and microscopic polyangiitis.

OBJECTIVE: Polyarteritis nodosa (PAN) has been used as a generic term for systemic vasculitis. The distinction between classic PAN and microscopic polyangiitis (MPA) has not always been made. The aims of this study were to compare the American College of Rheumatology (ACR) criteria for PAN with the Chapel Hill Consensus Conference (CHCC) definitions of classic PAN and MPA, and to estimate the annual incidence of PAN and MPA. METHODS: The 1990 ACR criteria and CHCC definitions for systemic vasculitis were applied to an unselected cohort of 130 patients with systemic vasculitis attending a single district hospital in the UK between February 1, 1988 and January 31, 1994. RESULTS: Eight patients who met the ACR criteria for PAN and who also met the CHCC definition of MPA but not classic PAN were identified. A further 5 patients met the CHCC definition of MPA but not the ACR criteria for any other type of systemic vasculitis. No patient who met the CHCC definition of classic PAN was identified. The annual incidence of MPA was calculated to be 3.6/million (95% confidence interval 1.7-6.9), and the annual incidence of PAN (ACR criteria) was 2.4/million (95% confidence interval 0.9-5.3). CONCLUSION: Classic PAN as defined by the CHCC is rare, because small vessel involvement is excluded from this definition.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

Wegener's granulomatosis--increased incidence or increased recognition?

We aimed to calculate the annual incidence of Wegener's granulomatosis (WG) in Norfolk (UK) and to compare the clinical spectrum of disease to that seen in tertiary centres in both the UK and USA. We also aimed to examine the seasonal onset of symptoms. This was a prospective study of all patients presenting with WG to a district hospital with a well-defined stable population (515,000) during the period 1988-1993. The annual incidence for WG in the adult population is 8.5/million (95% CI 5.2-12.9). These are the first incidence figures for a well-defined population and are higher than previously published. The clinical spectrum of disease in Norfolk was similar to that seen in tertiary centres and there is supportive evidence for a seasonal variation in the onset of symptoms (highest in winter).

Adult↗
PubMed1996

Inflammatory polyarthritis in the community is not a benign disease: predicting functional disability one year after presentation.

OBJECTIVE: To predict which patients with early inflammatory polyarthritis presenting to primary care will be functionally disabled one year after presentation, in order to inform treatment and referral decisions. METHODS: The study population consisted of 381 patients notified to the Norfolk Arthritis Register, a primary care based inception cohort of patients with inflammatory polyarthritis. Patients were regarded as functionally disabled if they had a Health Assessment Questionnaire (HAQ) score of one or more. Clinical, laboratory, and demographic variables easily measured at baseline were analyzed for their ability to predict future disability. Recursive partitioning was used to create a simple decision tree to predict those patients who would be disabled at one year. A logistic regression model was generated on a sample of 277 patients and tested on an independent sample of 104 patients. This was compared with other models, one of which consisted of the 1987 ARA criteria. RESULTS: 112 (29%) patients had a HAQ score of at least 1 at one year. The strongest predictors of future disability were a high baseline HAQ, large joint involvement, female sex, and longer disease duration. The decision tree predicted disability accurately in 67% of patients. CONCLUSION: It is possible to predict functional outcome at one year among patients with early inflammatory polyarthritis presenting to primary care using simple clinical variables measured at baseline. Satisfying the 1987 ARA criteria could not be used to predict future disability.

Adult↗
PubMed1995

Epidemiology of systemic vasculitis: changing incidence or definition?

The epidemiology of the systemic vasculitides is poorly documented. Many studies have been conducted from tertiary referral centers, with resulting problems of referral bias and uncertainty of denominator population, or have involved small populations. We have estimated the incidence of the major forms of systemic vasculitis in a stable, ethnically homogeneous population of 414,000 adults from 1988 to 1994. The overall annual incidence of systemic vasculitis (excluding giant cell arteritis) is 39/million (95% confidence intervals; ranging from 31 to 47). The annual incidence of Wegener's granulomatosis is 8.5/million (range, 5.2 to 12.9), Churg-Strauss syndrome 2.4/million (0.9 to 5.3), microscopic polyangiitis 2.4/million (0.9 to 5.3), adult Henoch-Schonlein purpura 1.2/million (0.3 to 3.5), and systemic rheumatoid vasculitis 12.5/million (8.5 to 17.7). These data suggest that the overall incidence of systemic vasculitis is greater than previously thought (10/million) with Wegener's granulomatosis and systemic rheumatoid vasculitis being the most common. Whether this represents a genuine increase in incidence or increased physician awareness is uncertain.

Churg-Strauss Syndrome↗