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Biomedical subjects

D J Hart

Publications and source records attributed to D J Hart.

At least 73 records · Page 4Linked to original sources

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↗

The relationship of obesity, fat distribution and osteoarthritis in women in the general population: the Chingford Study.

One thousand and three women aged 45-64 from the Chingford general population survey were studied cross sectionally to find the effect of quantity and distribution of body fat on the prevalence of radiologically confirmed osteoarthritis (OA) in the knee, carpometacarpal (CMC), distal interphalangeal (DIP), and proximal interphalangeal (PIP) joints. Obesity was classified as the upper tertile of body mass index (BMI kg/m2); the boundaries of the middle tertile were 23.4 and 26.4 kg/m2. The age adjusted odds ratio (OR) [and 95% confidence interval (CI)] of radiographic OA at the knee comparing the high and low tertile of BMI was 6.17 (3.26-11.71) and for bilateral knee radiographic OA was 17.99 (6.25-51.73). Comparing the middle and low tertile of BMI, the odds ratio for radiographic OA knee was 2.86 (1.44-5.68). For other joints the association between BMI and radiographic OA was less strong; the OR at CMC was 1.71 (1.05-2.78), at DIP was 1.52 (0.90-2.57), and at PIP was 1.23 (0.52-2.91). For all joints except PIP these OR increased if the diagnostic criteria included knee pain for at least a month, clinically evident swelling at the DIP or PIP, and pain or tenderness at the CMC. Recalled weight at age 20 years, or recalled maximum weight improved prediction of radiographic OA from current BMI, but measurement of fat distribution from circumference of waist, hip and thigh did not. Our results confirm that excess body weight is a powerful predictor of OA of the knee in middle aged women, and a modest predictor of DIP and CMC OA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Urinary collagen crosslinks reflect the radiographic severity of knee osteoarthritis.

The collagen crosslinks deoxypyridinoline and pyridinoline are indices of mature collagen breakdown and reflect increased bone turnover. Urinary levels were found to be significantly raised in a group of 59 women with knee OA compared to 110 female controls from the general population. Levels of the crosslinks correlated significantly with X-ray grade of all subjects including women from the general population with mild, often asymptomatic, disease. These correlations were not diminished after adjustment for age and weight.

Aged↗

Keratan sulphate in rheumatoid arthritis, osteoarthritis, and inflammatory diseases.

Serum concentrations of antigenic keratan sulphate determined by an enzyme linked immunosorbent assay (ELISA) with a monoclonal antibody were studied in patients with rheumatoid arthritis (RA), osteoarthritis, ankylosing spondylitis, other inflammatory diseases, and a large control group of women without arthritis. Mean keratan sulphate concentrations were low in 117 women with RA compared with 227 female control subjects matched for age drawn from a community survey. There were significant correlations between serum keratan sulphate concentrations in patients with RA and serum C reactive protein and the erythrocyte sedimentation rate. Serum keratan sulphate concentrations were also low in 29 men and women with ankylosing spondylitis and 29 patients with arthritis and high concentrations of C reactive protein. In 98 women undergoing an operation for benign breast disease there were decreases in serum keratan sulphate concentrations after the operation which correlated with doses in serum C reactive protein. No differences were found in keratan sulphate concentrations in 137 women with osteoarthritis compared with controls. Within the group with osteoarthritis there were no differences for the various joint groups and there was no obvious correlation with radiographic severity or progression. These findings suggest serum keratan sulphate is unlikely to be useful as a diagnostic marker in osteoarthritis or RA but indicate a role for inflammation in the regulation of cartilage loss.

Acute-Phase Reaction↗

Clinical signs of early osteoarthritis: reproducibility and relation to x ray changes in 541 women in the general population.

The definition and classification of early clinically apparent osteoarthritis both in clinical situations and in epidemiological surveys remains a problem. Few data exist on the between-observer reproducibility of simple clinical methods of detecting hand and knee osteoarthritis in the population and their sensitivity and specificity as compared with radiography. Two observers first studied the reproducibility of a number of clinical signs in 41 middle aged women. Good rates of agreement were found for most of the clinical signs tested (kappa = 0.54-1.0). The more reproducible signs were then tested on a population of 541 women, aged 45-65, drawn from general practice, screening centres, and patients previously attending hospital for non-rheumatic problems. The major clinical signs used had a high specificity (87-99%) and lower sensitivity (20-49%) when compared with radiographs graded on the Kellgren and Lawrence scale (2+ = positive). When analysis was restricted to symptomatic radiographic osteoarthritis, levels of sensitivity were increased and specificity was lowered. These data show that certain physical signs of osteoarthritis are reproducible and may be used to identify clinical disease. They are not a substitute for radiographs, however, if radiographic change is regarded as the 'gold standard' of diagnosis. As the clinical signs tested seemed specific for osteoarthritis they may be of value in screening populations for clinical disease.

Female↗

Frequency of osteoarthritis in hysterectomized women.

A previous retrospective study reported a 2-fold increase in hysterectomy rates in women outpatient clinical attenders with osteoarthritis (OA) compared to controls. Our study was undertaken to confirm the findings of a previous case-control study which suggested hysterectomy to be a risk factor for OA. A retrospective cohort study design was used that would reduce the problems of selection bias. One hundred and sixty-two women who had undergone a hysterectomy between 1978 and 1979 (current mean age 53.8) and 164 controls (mean age 54.1) were examined for peripheral joint OA between 1988 and 1989. The screening method was identical for both groups and included a questionnaire, systematic examination of certain joints and radiographs of hands and knees. Women with a previous hysterectomy were found to have significantly higher rates of clinical signs of knee OA and 1st carpometacarpal (CMC) OA than control women without hysterectomy. The results were confirmed when OA was classified by the presence of symptoms alone, and when only radiologically confirmed clinical cases were included. The application of radiological criteria showed significantly smaller medial joint spaces (by digital image analysis) in hysterectomized women, although no differences were found using the Kellgren and Lawrence grading system. The increased risk for knee and CMC persisted after adjustment for possible confounders including age, obesity, parity and smoking status. By contrast frequency of distal interphalangeal and proximal interphalangeal involvement was lower, though not significantly so, than in controls.

Arthrography↗

The use of radiographs in assessing the severity of knee osteoarthritis.

Conventional radiographic grading of the knee has been used for 30 years and is based around the presence of osteophytes. About 50% of subjects from the general population meeting traditional radiographic criteria are asymptomatic or have no signs of clinical disease. Recent development in the use of different radiographic grading systems involve more attention to joint space and categorization of discrete radiographic findings. These techniques include new grading scales that use a combination of separate radiographic features; microfocal radiography and digitized image analysis of joint space. It is hoped these might reflect more closely the pathological processes and correlate more closely with clinical severity.

Female↗

Detection of a human intracisternal A-type retroviral particle antigenically related to HIV.

Sjögren's syndrome is an autoimmune disease that is characterized by dryness of the mouth and eyes. The loss of salivary and lacrimal gland function is accompanied by lymphocytic infiltration. Because similar symptoms and glandular pathology are observed in certain persons infected with human immunodeficiency virus (HIV), a search was initiated for a possible retroviral etiology in this syndrome. A human intracisternal A-type retroviral particle that is antigenically related to HIV was detected in lymphoblastoid cells exposed to homogenates of salivary tissue from patients with Sjögren's syndrome. Comparison of this retroviral particle to HIV indicates that they are distinguishable by several ultrastructural, physical, and enzymatic criteria.

Centrifugation, Density Gradient↗

Detection of serum antibodies to retroviral proteins in patients with primary Sjögren's syndrome (autoimmune exocrinopathy).

Primary Sjögren's syndrome (SS) is considered a benign autoimmune disease; it is characterized by lymphoid infiltration of salivary and lacrimal glands, often accompanied by the presence of serum autoantibodies, particularly anti-Ro (SS-A) and anti-La (SS-B). There are important immunologic similarities between primary SS and acquired immunodeficiency syndrome. To investigate for a possible immune response to retroviral proteins in primary SS, we performed immunoblotting against human immunodeficiency virus-1 (HIV-1) proteins using sera from 47 patients with primary SS. Moderate-to-strong reactivity, suggesting the presence of serum antibodies, was found in 14 patients (30%). Of 120 normal subjects, only 1 showed moderate positivity. All 14 positive SS sera reacted against p24 (gag) but failed to react against gp41 or gp120 (env). This response did not reflect hypergammaglobulinemia since immunoglobulin concentrations among the 29 SS patients studied were the same in sera that contained and sera that did not contain anti-gag reactivity. Two sera also reacted against p17 gag. Four reacted against HIV-2 core proteins, but none reacted with core proteins of human T lymphotropic virus-I. Only 1 of the 14 sera reacted against Ro (SS-A), and 1 other reacted against La (SS-B). These results identify a subset of SS patients characterized by 1) the presence of serum antibodies to HIV-1 group-specific, but not type-specific, proteins, and 2) the relative absence of anti-Ro (SS-A) and anti-La (SS-B) autoantibodies. In this latter respect, these SS patients constitute a subpopulation that resembles patients with HIV-induced SS-like disease.

Adult↗

Changes in the hydrophobic-hydrophilic cell surface character of Halomonas elongata in response to NaCl.

Phase-partitioning studies of the euryhaline bacterium Halomonas elongata demonstrated that the hydrophobic-hydrophilic nature of the cell surface changed as the bacterium grew in different NaCl concentrations. Mid-log-phase cells grown in a high (3.4 M) NaCl concentration were more hydrophilic than were cells grown in a low (0.05 M) NaCl concentration. Mid-log-phase cells from defined medium containing 3.4 M NaCl normally produced a hydrophobicity reading of only 14 (hexadecane hydrophobicity = 100), while corresponding cells from defined medium containing 0.05M NaCl gave a hydrophobicity reading of 90. Compared with cells grown in low salt concentrations, cells grown in high salt concentrations were more hydrophilic at all stages of growth. Rapid suspension of log-phase cells grown in 1.37 M NaCl into a 0.05 or 3.4 M NaCl solution produced no detectable rapid changes in surface hydrophobicity. These data suggest that as H. elongata adapts to different NaCl concentrations, it alters the affinity of its outermost cell surface to water.

Cell Membrane↗

Ester-imine condensations: preparation of racemic intermediates for the synthesis of the carbapenem antibiotics PS-5 and PS-6.

The lithium enolates of ethyl butyrate and ethyl isovalerate react with N-p-methoxyphenylcinnamaldimine in tetrahydrofuran (THF)-hexamethylphosphoric triamide (HMPA) to afford predominantly trans beta-lactams 9 (67%) and 20 (78%), respectively. beta-Lactam 9 was converted to PS-5 intermediate 18 in 21% overall yield (8 steps). Beta-lactam 20 was converted to PS-6 analog 28 in 22% overall yield using an eight step sequence.

Anti-Bacterial Agents↗