Host response to successive challenges with lentogenic and velogenic Newcastle disease virus in local chickens of Ghana.

Newcastle disease (ND) is a highly contagious viral disease that constantly threatens poultry production. The velogenic (highly virulent) form of ND inflicts the most damage and can lead to 100% mortality in unvaccinated village chicken flocks. This study sought to characterize responses of local chickens in Ghana after challenging them with lentogenic and velogenic Newcastle disease virus (NDV) strains. At 4 wk of age, chicks were challenged with lentogenic NDV. Traits measured were pre- and post-lentogenic infection growth rates (GR), viral load at 2 and 6 d post-lentogenic infection (DPI), viral clearance rate and antibody levels at 10 DPI. Subsequently, the chickens were naturally exposed to velogenic NDV (vNDV) after anti-NDV antibody titers had waned to levels ≤1:1,700. Body weights and blood samples were again collected for analysis. Finally, chickens were euthanized and lesion scores (LS) across tissues were recorded. Post-velogenic exposure GR; antibody levels at 21 and 34 days post-velogenic exposure (DPE); LS for trachea, proventriculus, intestines, and cecal tonsils; and average LS across tissues were measured. Variance components and heritabilities were estimated for all traits using univariate animal models. Mean pre- and post-lentogenic NDV infection GRs were 6.26 g/day and 7.93 g/day, respectively, but mean post-velogenic NDV exposure GR was -1.96 g/day. Mean lesion scores ranged from 0.52 (trachea) to 1.33 (intestine), with males having significantly higher (P < 0.05) lesion scores compared to females. Heritability estimates for the lentogenic NDV trial traits ranged from moderate (0.23) to high (0.55) whereas those for the vNDV natural exposure trial were very low (≤ 0.08). Therefore, in contrast to the vNDV exposure trial, differences in the traits measured in the lentogenic challenge were more affected by genetics and thus selection for these traits may be more feasible compared to those following vNDV exposure. Our results can form the basis for identifying local chickens with improved resilience in the face of NDV infection for selective breeding to improve productivity.

Physiological responses to heat stress in two genetically distinct chicken inbred lines.

High ambient temperature is one of the most important environmental factors negatively impacting poultry production and health. Genetics is an important contributor in mitigating the stress response to heat. Two genetically distinct highly inbred lines of similar body size (Leghorn and Fayoumi) were characterized for phenotypic differences in response to heat. At 14 days of age, birds were exposed to 38°C with 50% humidity for 4 hours, then 35°C until the conclusion of the experiment. Non-treated individuals were kept at 29.4°C for the first week and then 25°C throughout the experiment. Birds in the heat-stress group were inoculated at day (d) 21 with Newcastle disease virus (NDV) La Sota strain to investigate the effects of heat stress and NDV infection. Thirteen blood parameters were measured using the iSTAT blood analyzer at three stages: 4 h, 6 d, and 9 d post heat-stress treatment, representing acute heat (AH) exposure, chronic heat (CH1) exposure, and chronic heat exposure after virus infection (CH2), respectively. Most blood parameters were significantly changed with heat stress in Leghorns at AH and in Fayoumis at CH1 and CH2. The Leghorn line had significant acute responses with disrupted acid-base balance and metabolic disorders. The heat-resilient Fayoumis maintained a relatively well-balanced acid-base balance. The current study provides the comprehensive profile of biomarker signatures in blood associated with heat tolerance and suggests that PO2, TCO2, HCO3, and base excess can be served as potential biomarkers that can be used to genetically improve heat tolerance in poultry.

Assessment of a Self-Reported Drinks Diary for the Estimation of Drinks Intake by Care Home Residents: Fluid Intake Study in the Elderly (FISE).

OBJECTIVES: We evaluated the accuracy of a newly developed self-completed Drinks Diary in care home residents and compared it with direct observation and fluid intake charts. DESIGN: Observational study. SETTING: Residential care homes in Norfolk, UK. PARTICIPANTS: 22 elderly people (18 women, mean age 86.6 years SD 8.6, 12 with MMSE scores <27). MEASUREMENTS: Participants recorded their own drinks intake over 24 hours using the Drinks Diary while care staff used the homes' usual fluid intake chart to record drinks intake. These records were compared with drinks intake assessed by researcher direct observation (reference method), during waking hours (6am to 10pm), while drinks taken from 10pm to 6am were self-reported and checked with staff. RESULTS: Drinks intake assessed by the Drinks Diary was highly correlated with researcher direct observation (Pearson correlation coefficient r=0.93, p<0.001, mean difference -163ml/day) while few staff-completed fluid charts were returned and correlation was low (r=0.122, p=0.818, mean difference 702ml/day). The Drinks Diary classified 19 of 22 participants correctly as drinking enough or not using both the European Food Safety Authority and US recommendations. CONCLUSION: The Drinks Diary estimate of drinks intake was comparable with direct observation and more accurate (and reliably completed) than staff records. The Drinks Diary can provide a reliable estimate of drinks intake in elderly care home residents physically and cognitively able to complete it. It may be useful for researchers, care staff and practitioners needing to monitor drinks intake of elderly people, to help them avoid dehydration.

Association of morbid obesity with disability in early inflammatory polyarthritis: results from the Norfolk Arthritis Register.

OBJECTIVE: Obesity has been associated with disease outcomes in inflammatory arthritis. This study aimed to investigate cross-sectionally the relationship between body mass index (BMI) and functional disability in a large inception cohort of patients with early inflammatory polyarthritis (IP). METHODS: Patients age ≥16 years with ≥2 swollen joints for ≥4 weeks were recruited into the Norfolk Arthritis Register. At the initial assessment, clinical and demographic data were obtained, joints were examined, and height and weight were measured. Blood samples were taken to measure inflammatory markers and autoantibodies, and patients completed the Health Assessment Questionnaire (HAQ) to assess functional disability. Univariate and multivariate ordinal regression were used to examine the cross-sectional association between BMI and the HAQ. Multiple imputation using chained equations allowed inclusion of patients with missing variables. RESULTS: A total of 1,246 patients were studied (median age 57 years). Of those patients, 782 patients (63%) were female and 303 (25%) were obese (BMI ≥30 kg/m(2) ). Morbid obesity (BMI ≥35 kg/m(2) ) was significantly associated with worse functional disability in the univariate and multivariate analysis with missing data imputed, adjusting for age, sex, symptom duration, smoking status, disease activity, autoantibodies, comorbidities, and treatment (multivariate odds ratio 1.87, 95% confidence interval 1.14-3.07). CONCLUSION: Morbid obesity in patients with early IP is associated with worse HAQ scores. This should be taken into account in patient management and when interpreting the HAQ in clinical practice.

Multiple adverse pregnancy outcomes before symptom onset are associated with a worse disease outcome in women with recent-onset inflammatory polyarthritis.

OBJECTIVE: Previous evidence suggests that women with a history of adverse pregnancy outcomes (APOs) may be at greater risk of developing rheumatoid arthritis. Additionally, one study reported that female patients with rheumatoid arthritis with a history of preonset APOs showed a worse 2-year radiographic outcome than did patients with no APOs. The authors' aim was to investigate the relationship between preonset APOs (spontaneous abortion or stillbirth) and disease outcome in women with inflammatory polyarthritis (IP). METHODS: The Norfolk Arthritis Register (NOAR) is a primary-care-based cohort of patients with recent-onset IP; 1586 gravid women who joined NOAR during 1990-2004 were included in this analysis. The authors examined the relationship between patient-reported preonset APOs and disease outcome, measured using the Health Assessment Questionnaire (HAQ) and disease activity score in 28 joints (DAS28(CRP)) (for a subgroup of patients), using linear random effects analysis, adjusted for age and other factors. RESULTS: In a predominantly parous cohort (99%), 397 (25%) women reported ≥1 APO before symptom onset. The rates of APOs in NOAR were comparable to the general population. On average, women with a history of ≥2 APOs had significantly higher HAQ and DAS28 scores over time than women with no APOs (mean difference in HAQ 0.13 (95% CI 0.002 to 0.26); DAS28, 0.56 (95% CI 0.01 to 1.11)). This relationship was more pronounced in women with ≥3 APOs (mean difference in HAQ 0.23 (95% CI 0.02 to 0.43); DAS28, 0.98 (95% CI 0.23 to 1.74)). CONCLUSION: Women with two or more APOs before IP onset had a worse disease outcome than women with no APOs.

A genetic marker at the OLIG3/TNFAIP3 locus associates with methotrexate continuation in early inflammatory polyarthritis: results from the Norfolk Arthritis Register.

Whole-genome association studies in rheumatoid arthritis have identified single-nucleotide polymorphisms (SNPs) predisposing to disease with moderate risk. We aimed to investigate the role of these markers in predicting methotrexate (MTX) response, measured by continuation on MTX monotherapy in patients with recent onset inflammatory polyarthritis (IP). In all, 19 SNPs were genotyped in 736 patients treated with MTX following registration, or not more than 3 months before registration, to the Norfolk Arthritis Register. The association of SNPs with MTX continuation by year 1 and by year 2 was investigated using Cox proportional hazard regression models. A SNP within the OLIG3/TNFAIP3 locus (rs6920220) was associated with being less likely to maintain MTX monotherapy at year 1, hazards ratio (HR) 1.73 (1.18, 2.52) and year 2, HR 1.49 (1.11, 2.00); correlating with an increased in adverse events. Weak evidence for an effect at the PTPN22 locus was also observed. These findings require replication in other large datasets.

The relationship between oral contraceptive use and functional outcome in women with recent-onset inflammatory polyarthritis: results from the Norfolk Arthritis Register.

OBJECTIVE: Use of oral contraceptives (OCs) may prevent the development of rheumatoid arthritis, but the influence of OC use on disease outcome is unresolved. The purpose of this study was to examine functional outcome and OC use in women with inflammatory polyarthritis (IP). METHODS: The Norfolk Arthritis Register (NOAR) is an inception cohort of patients with recent-onset IP. We studied patient-reported history of OC use in 663 women who were born after 1945 and who had not used OCs during followup. OC use during followup was additionally investigated in 265 women who were <50 years old and had not undergone menopause or hysterectomy during followup. All patients were recruited to the NOAR between 1990 and 2004. Functional ability was assessed using the Health Assessment Questionnaire (HAQ), with adjustment for age at symptom onset. RESULTS: The median followup was 4.9 years. In the investigation analyzing OC use before symptom onset, patients who had used OCs before symptom onset had lower HAQ scores throughout followup than patients who had not taken OCs before symptom onset (difference in score at 5-year followup -0.35; 95% confidence interval [95% CI] -0.51, -0.19). Patients who were taking OCs at baseline had lower HAQ scores over time than women who were not taking OCs at baseline but had previously done so (mean difference -0.21; 95% CI -0.40, -0.02). In the investigation analyzing OC use during followup, OC use during followup was associated with lower HAQ scores over time than no OC use during followup (mean difference -0.06; 95% CI -0.16, 0.03); however, this was only significant for women with moderate or severe functional disability at the previous assessment (mean difference -0.23; 95% CI -0.40, -0.07). Further adjustment for potential confounders and exclusion of hormone replacement therapy users had little impact. CONCLUSION: OC use is generally associated with a beneficial functional outcome in IP, and use before and at symptom onset appeared to have the most consistent benefit.

Parity, time since last live birth and long-term functional outcome: a study of women participating in the Norfolk Arthritis Register.

OBJECTIVE: To investigate the relationship between pre-symptom onset live births and functional outcome in women with inflammatory polyarthritis (IP). METHODS: 1872 women with no subsequent pregnancies were registered with the Norfolk Arthritis Register between 1990 and 2004 and followed-up for a median of 5 years. Functional disability over time was assessed by Health Assessment Questionnaire (HAQ). The number and calendar year of past live births were recorded. Differences in HAQ score over time by parity and time since last live birth (latency), adjusted for age and symptom duration, were examined using linear random effects models. The results were then adjusted for a number of potential confounders. RESULTS: 1553 women (83%) had ≥1 live births before symptom onset. The median latency was 26 years (IQR 16-35). Parous women had significantly lower HAQ scores over time than nulliparous women (-0.19, 95% CI -0.32 to -0.06). Increasing latency was associated with increasing HAQ score; the mean HAQ score of women with a latency of approximately 32 years was the same as for nulliparous women. This was independent of autoantibody status, socioeconomic status, smoking history and comorbidity. CONCLUSION: Parous women who develop IP have better functional outcome over time than nulliparous women who develop IP. The beneficial effect of parity diminishes with time.

The relationship between post-onset pregnancy and functional outcome in women with recent onset inflammatory polyarthritis: results from the Norfolk Arthritis Register.

OBJECTIVE: To examine the influence of post-symptom-onset pregnancy on disease outcome in women with inflammatory polyarthritis (IP). METHODS: A total of 631 women, aged <48 years at symptom onset, were registered with the Norfolk Arthritis Register (NOAR) between 1990 and 2004. Functional disability was assessed using the Stanford Health Assessment Questionnaire (HAQ). Blood was tested for rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA). The date and outcome of all pregnancies were reported during a median follow-up of 7 years. Linear random effects models were used to examine HAQ score over time, by pregnancy status. RESULTS: were then stratified for RF and ACPA status. Results In all, 72 women had a post-onset pregnancy (Po-P) including 45 women who were pregnant at a follow-up assessment. Pregnancy was generally associated with lower HAQ scores over time than non-pregnancy. The 10 ACPA-positive women who had a Po-P had significantly worse subsequent HAQ scores. CONCLUSION: Overall, Po-P is associated with lower HAQ scores, compared to no Po-P. This may reflect a beneficial effect of pregnancy on disease outcome, or that predominantly women with milder disease become pregnant. In women with the worst predicted outcome (APCA positive), Po-P is associated with a worse outcome than no pregnancy.

Can clinical factors at presentation be used to predict outcome of treatment with methotrexate in patients with early inflammatory polyarthritis?

PURPOSE: Methotrexate (MTX) is the first choice conventional disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis. It is not universally effective, however; although to date it is not possible to predict with any accuracy which patients will respond to treatment. The aim of this analysis was to examine whether clinical and genetic variables could be used to predict response to MTX. METHODS: Patients recruited to the Norfolk Arthritis Register (NOAR), a primary care based inception cohort of patients with inflammatory polyarthritis, were eligible for this analysis if they were commenced on MTX as their first DMARD within 3 months of their baseline visit and had at least 2 years of follow-up data. Outcome on MTX was defined as: (1) stopped for adverse events; (2) stopped for inefficacy or second DMARD added; (3) stopped for other reasons; or (4) remained on MTX monotherapy. Multiple logistic regression was used to establish which variables (including demographics, disease activity and Health Assessment Questionnaire score) predicted stopping monotherapy for inefficacy or adverse event (with those remaining on treatment taken as the referent category). The area under the Receiver Operating Characteristic curves (AUC ROC), were used to determine how accurate the model was at predicting outcome. RESULTS: 309 patients were included in this analysis. At 1 year (2 years), 34 (46) patients had stopped for adverse events and 25 (49) had either stopped monotherapy for inefficacy or had a second DMARD added. 231 (188) patients remained on MTX monotherapy. The strongest predictor of inefficacy at both time points was shared epitope positivity: odds ratios (OR) 5.8 (95% confidence intervals (CI) 1.3 to 25.6) at 1 year, OR 3.0 (95% CI 1.3 to 7.3) at 2 years. High Health Assessment Questionnaire score (OR 1.84 95% CI 1.12 to 3.01) and female gender (OR 2.2, 95% CI 0.92 to 5.28) were associated with adverse events on MTX at 1 year. However, even the most optimal combinations of the factors analysed were only weakly predictive of treatment outcome: AUC ROC for adverse events 0.68 (95% CI 0.58 to 0.78) and for inefficacy AUC ROC 0.71 (95% CI 0.6 to 0.81). CONCLUSIONS: Within this cohort, routine clinical and laboratory factors were poor at predicting outcome of treatment with MTX. Given the major therapeutic advantage to be derived from accurate prediction of treatment outcome, further studies will need to investigate novel biological and other markers.

Five-year outcome of a primary-care-based inception cohort of patients with inflammatory polyarthritis plus psoriasis.

OBJECTIVES: To establish whether patients with inflammatory arthritis plus psoriasis have a different outcome from those who do not have psoriasis. METHODS: Seventy-nine patients with inflammatory arthritis plus psoriasis were recruited by the Norfolk Arthritis Register (NOAR) in 1990-94 and followed for 5 yrs. Their outcome was compared with the remainder (n = 755) of the NOAR cohort. We then restricted the analysis to subjects who were rheumatoid factor (RF)-negative, and compared those with and without psoriasis. Outcomes studied included remission, deformed joint count, the presence and extent of erosive damage and physical function. RESULTS: Patients with psoriasis were younger, more likely to be male, less likely to be RF-positive and more likely to have been treated with disease-modifying drugs than patients without psoriasis. After adjustment for age, gender and treatment, the only differences between the psoriasis and non-psoriasis groups were in RF positivity (adjusted odds ratio 0.44; 95% CI 0.25, 0.78) and in the Larsen score in patients with erosions. CONCLUSIONS: Patients with inflammatory arthritis plus psoriasis have a similar outcome to other RF-negative patients with arthritis.

The performance of anti-cyclic citrullinated peptide antibodies in predicting the severity of radiologic damage in inflammatory polyarthritis: results from the Norfolk Arthritis Register.

OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are a stronger predictor of the severity of rheumatoid arthritis than is rheumatoid factor (RF). Their role in predicting outcome in unselected patients with new-onset inflammatory polyarthritis (IP) has not been examined. The aims of this study were to examine the role of baseline RF and anti-CCP antibodies in determining the likelihood of patients having erosions at presentation or in predicting future radiologic damage, and to determine whether anti-CCP antibodies or RF is sufficiently robust to be clinically useful in guiding treatment decisions in early IP. METHODS: Patients were recruited from the Norfolk Arthritis Register. Logistic regression models were fitted to test the ability of anti-CCP antibodies and RF to predict erosions. Further models were investigated to examine the role of anti-CCP antibodies in patients stratified by RF status. RESULTS: The presence of anti-CCP antibodies at baseline was strongly associated with both prevalent erosions (odds ratio [OR] 2.53 [95% confidence interval (95% CI) 1.48-4.30]) and developing erosions at 5 years (OR 10.2 [95% CI 6.2-16.9]). These ORs were higher than those for RF (OR 1.63 [95% CI 0.94-2.82] and OR 3.4 [95% CI 2.2-5.2], respectively). The likelihood ratio (LR) for the prediction of prevalent erosions and erosions at 5 years was highest in the RF-subgroup (LR 2.2 and 5.8, respectively). However, 27% of anti-CCP-patients had developed erosions by 5 years. CONCLUSION: Despite their strong association with the presence, development, and extent of erosions, anti-CCP antibodies alone are not a sufficiently accurate measure upon which to base clinical treatment decisions. Knowledge of anti-CCP antibody status is most informative in RF-negative patients.

Comparing the long-term clinical outcome of treatment with methotrexate or sulfasalazine prescribed as the first disease-modifying antirheumatic drug in patients with inflammatory polyarthritis.

OBJECTIVE: To compare the clinical and functional outcome at 2 and 5 years in patients with inflammatory polyarthritis treated with either methotrexate (MTX) or sulfasalazine (SSZ) as the first disease-modifying antirheumatic drug (DMARD). METHODS: Patients recruited to a primary-care-based inception cohort of patients with inflammatory polyarthritis were eligible for this analysis if they were started on either SSZ (n = 331) or MTX (n = 108) as their first DMARD within 3 months. Outcomes assessed included the Disease Activity Score (DAS)28, Health Assessment Questionnaire, radiological erosions (Larsen Score) and cumulative mortality with the proportions still on the original treatment. To overcome potential bias in allocation to these two treatments, a propensity score was calculated based on baseline disease status variables. RESULTS: are expressed as the mean difference between MTX and SSZ, both unadjusted and adjusted for propensity score. RESULTS: The baseline differences between the two groups disappeared after adjusting for propensity score. At 2 and 5 years there were few differences in the clinical outcomes, either unadjusted or after adjustment for propensity. By contrast, at 5 years the proportion that was erosive was lower in the MTX group: odds ratio 0.3 (95% confidence interval 0.1 to 0.8), with a 31% lower Larsen Score after adjustment. At both time points, those treated with MTX were at least twice as likely to remain on that drug as those treated with SSZ. CONCLUSION: Long-term clinical outcome is similar in patients prescribed MTX and SSZ, although it would seem that MTX has greater potential to suppress erosions, which supports it being the first DMARD of choice.

Incidence of lymphoma in a large primary care derived cohort of cases of inflammatory polyarthritis.

OBJECTIVE: To determine the risk of lymphoma in a primary care derived cohort of new onset cases of inflammatory polyarthritis and assess the contribution of disease severity and standard immunosuppressive treatment. DESIGN: Prospective cohort study. METHODS: 2105 subjects with new onset inflammatory polyarthritis were recruited to the Norfolk Arthritis Register (NOAR) and followed annually for (median) 8.4 years. Occurrence of lymphoma was determined by annual morbidity review and linkage to the central hospital database serving the NOAR area. Cases of lymphoma were verified by record review. Standardised incidence ratios (SIRs) for lymphoma were calculated compared with the local, age, sex, and calendar year expected rates. Stratified analyses were undertaken for various markers of disease severity and treatment history. RESULTS: There were 11 cases of lymphoma during 15,548 person years of follow up, the majority of which were of large B cell type. Compared with the local population the SIR was 2.4 (95% confidence interval, 1.2 to 4.2). The risks in cases classified as rheumatoid arthritis, ever rheumatoid factor positive, or ever treated with DMARDs were all higher, the highest risk group being those treated with methotrexate: SIR = 4.9 (1.8 to 10.6). CONCLUSIONS: There was a doubling in risk of lymphoma in new onset cases of inflammatory polyarthritis. Patients with the most severe disease were twice as likely as other patients to develop lymphoma. These results need to be taken into account when considering reported increased risks of lymphoma compared to background population risk in users of new biological agents.

The NOAR Damaged Joint Count (NOAR-DJC): a clinical measure for assessing articular damage in patients with early inflammatory polyarthritis including rheumatoid arthritis.

OBJECTIVES: To evaluate the reliability and validity of the Norfolk Arthritis Register Damaged Joint Count (NOAR-DJC) in patients with early inflammatory polyarthritis (IP). METHODS: The NOAR-DJC examines deformity in 51 joints. Deformity is defined as inability to adopt the anatomical position, reduction in range of movement by at least one-third, and/or surgical alteration of the joint. Reliability was investigated by assessing intra- and inter-observer agreement in 40 and 32 patients, respectively. Validity was assessed by correlating the NOAR-DJC with the eroded joint count (criterion validity), the Health Assessment Questionnaire (HAQ) (convergent construct validity) and tender and swollen joint counts (divergent construct validity) and by discriminating between those who did and did not satisfy criteria for rheumatoid arthritis (discriminant validity). RESULTS: The intraclass correlation coefficient for the intra- and inter-rater studies were 0.88 [95% confidence interval (CI) 0.79, 0.94, P<0.00001] and 0.74 (95% CI 0.53, 0.86, P<0.00001), respectively. Correlations with eroded joint counts and HAQ scores after 5 yr follow-up were r(s) = 0.42 (95% CI 0.35, 0.49, P<0.01) and r(s) = 0.45 (95% CI 0.4, 0.5, P<0.01), respectively. Correlations with tender and swollen joint counts were weak (r(s) = 0.28 and r(s) = 0.33). CONCLUSION: The NOAR-DJC is a quick, reliable and valid tool for assessing articular damage in patients with early IP.

Vitamin C and the risk of developing inflammatory polyarthritis: prospective nested case-control study.

OBJECTIVE: To investigate whether, there is an association between consumption of fruit and vegetables and dietary antioxidants and the risk of developing inflammatory polyarthritis (IP). METHODS: In a prospective, population based, nested case-control study of residents of Norfolk, UK, men and women aged 45-74 years were recruited, between 1993 and 1997 through general practice age-sex registers to the Norfolk arm of the European Prospective Investigation of Cancer (EPIC-Norfolk). Dietary intake was assessed at baseline using 7 day diet diaries. Seventy three participants who went on to develop IP between 1993 and 2001 and were registered by the Norfolk Arthritis Register (NOAR) were identified. Incident cases of IP, assessed by general practitioners, fulfilled the criteria of two or more swollen joints, persisting for a minimum of 4 weeks. Each case of IP was matched for age and sex with two controls free of IP. RESULTS: Lower intakes of fruit and vegetables, and vitamin C were associated with an increased risk of developing IP. Those in the lowest category of vitamin C intake, compared with the highest, increased their risk of developing IP more than threefold, adjusted odds ratio (OR) with 95% confidence intervals (CI) 3.3 (95% CI 1.4 to 7.9). Weak inverse associations between vitamin E and beta-carotene intake and IP risk were found. CONCLUSION: Patients with IP (cases) consumed less fruit and vitamin C than matched controls, which appeared to increase their risk of developing IP. The mechanism for this effect is uncertain. Thus similar studies are necessary to confirm these results.

Traditional cardiovascular risk factors measured prior to the onset of inflammatory polyarthritis.

BACKGROUND: Cardiovascular mortality is increased in patients with seropositive inflammatory polyarthritis (IP). We tested the hypothesis that the increased risk of cardiovascular disease (CVD) can be explained by elevated traditional CVD risk factor levels in persons prior to development of IP. METHODS: In a population-based, prospective nested case-control study, 25 600 people aged 45-75 yr participated in a health survey, including standard CVD risk factor assessment, between the years 1993 and 1997. There were 91 incident IP cases (one-third were seropositive at presentation) identified during follow-up to the end of July 2001. Baseline CVD risk factors in the IP cases were compared with those in two age/gender-matched controls. RESULTS: Current smokers had an odds ratio of 2.0 (95% CI 1.0-4.0) for IP. Other risk factors, including total and LDL cholesterol, systolic and diastolic blood pressure and obesity, did not differ significantly between cases and controls. Importantly, in combination, using a standard coronary disease risk score, these factors only had a modest association with future IP, and no association when analysis was restricted to the smaller number of cases who were seropositive. CONCLUSION: Of the traditional cardiovascular risk factors, only smoking increases CVD risk prior to the onset of IP. Therefore the increased CVD observed in these patients is likely to be a consequence of factors operating after the onset of the arthritis.

The pharmacokinetics of anti-thymocyte globulin (ATG) following intravenous infusion in man.

The pharmacokinetics of the distribution and elimination of polyclonal rabbit antithymocyte globulin (ATG) following intravenous infusion was studied in patients who had received renal allografts. ATG concentration was measured using a new enzyme-linked immunoabsorbent assay (ELISA) for the Fc portion of rabbit IgG. Eleven patients received 14 courses of ATG supplied either by Fresenius (F-ATG) or Merieux (M-ATG) as a daily infusion of 2-6 mg/kg body weight for a therapeutic course lasting 5-10 days. The washout phase of ATG elimination was analysed over 0-300 days; results were well-fitted by a single exponential decay (r2 > 0.95) giving a mean elimination half-life (t0.5e) of 29.8 days (range 14.3-45.0, n = 9). Data for the first 4 days of treatment were analysed with linear regression to obtain a mean value for the apparent volume of distribution of ATG (Vd) of 0.12 l/kg body weight (range 0.07 to 0.17, n = 5). These results demonstrate that rabbit ATG has a long half-life in human plasma and an apparent volume of distribution of about twice plasma volume. The relationship between the concentration of ATG measured by this Fc receptor assay and its biological activity requires further study.

Clinical and biochemical observations on three cases of hypoxanthine-guanine phosphoribosyltransferase deficiency.

Clinical and enzymatic studies on two brothers with severe deficiencies of erythrocyte hypoxanthineguanine phosphoribosyltransferase (HGPRTase) are described, and are compared with similar studies of a classical case of the Lesch-Nyhan syndrome from another family. The two brothers have no neurological abnormalities, only traces of erythrocyte HGPRTase, erythrocyte adenine phosphoribosyltransferase activities approaching the high levels found in the Lesch-Nyhan patient, and similarly raised plasma and urinary concentrations of uric acid. Despite these strong biochemical similarities between the three patients, there were wide differences in the clinical case histories. In both families the enzyme deficiency appeared to be inherited as an X-linked character through asymptomatic carrier females. The relationship of HGPRTase deficiencies to the Lesch-Nyhan syndrome is discussed. Some observations relating to techniques are reported. Cellulose acetate has been found to give much better separations of labelled reaction products in low-level phosphoribosyltransferase assays than filter paper, when used as a supporting medium for electrophoresis. The analysis of hair follicles gives indications of individuals heterozygous for the enzyme deficiency, but the proportion of enzyme-deficient follicles was very small, and the test needs support from studies of other cell types. Using haemolysates, there were signs of a slow indirect conversion of hypoxanthine to inosinic acid, via inosine. Inosine appears to be labelled by a ribosyl-transfer reaction.