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Biomedical subjects

T D Spector

Publications and source records attributed to T D Spector.

At least 181 records · Page 10Linked to original sources
PubMed1993

Protective effect of androgens against inflammation induced cartilage degradation in male rodents.

OBJECTIVES: Rheumatoid arthritis (RA) is a disease which predominantly affects women. Interestingly, low serum androgen levels and clinical improvement with androgen replacement have been reported in male patients. The aetiopathogenic role of sex hormones in arthritis and their potential long term effects on joint destruction and disability remains unclear, however. This study was designed to investigate the potential influence of sex hormones on inflammation induced cartilage degradation in male rodents. METHODS: An in vivo model of cotton wrapped cartilage implants was used to assess the effects of androgen, oestradiol, and progesterone on inflammation induced cartilage degradation, and in vitro techniques were used to investigate the direct actions on cartilage metabolism and cytokine production in male animals. RESULTS: Orchidectomy resulted in accelerated cartilage damage which was reversed by replacement of physiological levels of androgens. Granulomatous tissue from castrated male rodents produced higher amounts of interleukin 1. Sex hormones reduced spontaneous proteoglycan loss in vitro but did not interfere with the effects of interleukin 1 on cultured cartilage. CONCLUSIONS: Androgens appear to protect cartilage from inflammation induced breakdown in male animals. These results support a pathogenic role for hypoandrogenism in rheumatoid arthritis and suggest that long term androgen replacement may help prevent joint damage and disability.

Androgens↗
PubMed1993

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↗
PubMed1992

Do current regimes of hormone replacement therapy protect against subsequent fractures?

It is now accepted that unopposed oestrogen therapy reduces osteoporotic fractures by about 50%. Although current regimes with added progestogens are thought to act similarly to unopposed oestrogens, no study has yet demonstrated an effect on fractures with the former. Using a retrospective cohort design we studied fracture rates in women attending a menopause clinic for hormone replacement therapy (HRT) and compared them with women derived from the general population. Data were analysed from 1075 women exposed to HRT and 1741 non-exposed postmenopausal women. In all 226 fractures were reported between 1977 and 1986, the commonest site being the distal radius, occurring in 28 of the HRT women and in 37 of the non-exposed women. The incidence density rate for fracture of the distal radius is 3.5/1000 woman-years (wy) in non-exposed women. This was similar to the rate in the HRT women prior to HRT use, the rate falling by 30% after exposure from 3.2 to 2.2/1000 wy. The protective effect on osteoporotic fractures increased progressively with duration of use. After 5 years of use the relative risk fell to 0.5 (95% confidence interval, 0.2-1.2) for all osteoporotic fractures and for the distal radius to 0.18 (95% confidence interval, 0.05-1.3). No similar changes were seen for non-osteoporotic fractures. There were 6 (0.6/1000 wy) reported fractures of the hip in the non-exposed group compared with none in the HRT group (when 1.7 were expected based on non-exposed rates) (p = 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The role of pregnancy in the course and aetiology of rheumatoid arthritis.

The aetiology of rheumatoid arthritis (RA) is unknown, although being female is generally recognized as the most important independent risk factor, the disease being 2 to 3 times more frequent in females than in males. The dramatic effect of pregnancy in rheumatoid arthritis has been documented for over 50 years. This review examines the evidence and possible mechanisms by which pregnancy modifies the disease process and may alter predisposition to the development of RA in later life.

Arthritis, Rheumatoid↗
PubMed1992

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↗
PubMed1992

Sibship size does not increase the risk of developing rheumatoid arthritis.

Although the cause of rheumatoid arthritis (RA) is unknown, one hypothesis is that an infectious episode may trigger the disease and this may occur in childhood. Observational studies performed at least 25 years ago have suggested that the incidence of RA is increased in individuals from large families. We therefore tested this hypothesis using data from a case-control study of 218 females with RA aged 35-70 (mean 58.9 years) and 210 similar aged osteoarthritis (OA) females. Information was obtained by postal questionnaire on sibship size, position in family and sex ratio of siblings. No significant differences were found between the cases and controls for any of these variables. This study did not support the hypothesis that early childhood infection as a consequence of overcrowding is an important factor in the development of RA.

Aged↗
PubMed1992

Radiological progression of osteoarthritis: an 11 year follow up study of the knee.

A follow up study was carried out in 1990 on 169 well documented patients initially presenting with osteoarthritis of the hands or knees between 1975 and 1977. Radiographic change in the knee was used as the outcome measure. Sixty three subjects had paired knee radiographs a mean of 11 years apart and were 69 (range 52-87) years old at follow up. Thirty subjects were known to have died, 28 were untraceable, and 48 were traced but did not have paired films available. The films were read independently and blind to time sequence by two observers using five different radiological scoring methods. Most of the knees did not increase in Kellgren and Lawrence grade, with only 33% deteriorating over the time period. The results were similar when a subject was categorised by their worst knee. When a more sensitive global score on paired films was used 50% of knees showed a slight deterioration and 10% improved. Visual analogue pain scores remained unchanged. Those with knee pain at baseline had a greater chance of progressing, as did those with existing osteoarthritis in the contralateral knee. These results suggest that most patients with osteoarthritis attending rheumatology clinics do not deteriorate radiographically or symptomatically over an 11 year period. More work is needed in the selection and early detection of subjects with a poor prognosis and in focusing early intervention on this high risk group.

Aged↗
PubMed1992

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↗
PubMed1992

Use of a risk factor and dietary calcium questionnaire in predicting bone density and subsequent bone loss at the menopause.

One hundred and thirty six healthy white females within 30 months of their last menstrual period (mean age 52 years) were examined to determine the usefulness of a risk factor questionnaire in predicting bone density and subsequent loss. Bone density was assessed at baseline and at 12 monthly intervals. None of the proposed risk factor variables with the exception of nulliparity correlated with the baseline spinal or femoral bone density. As a predictor of bone loss only drinking alcohol (more than four units/day) was significant. A risk factor score derived from the questionnaire before its administration did not correlate with baseline bone density or subsequent bone loss. In most normal women questioned soon after a natural menopause, an estimate of bone density and subsequent bone loss and hence osteoporotic risk cannot be reliably made using a simple risk factor questionnaire.

Alcohol Drinking↗
PubMed1991

Endogenous sex steroid levels in women with generalised osteoarthritis.

Epidemiologic and clinical observations have suggested a relationship between generalised osteoarthritis (GOA) and hormonal and menopausal factors in women. We explored the hypothesis that postmenopausal women with GOA have altered sex hormone status compared with control women. We studied 112 women (mean age 64) with GOA. Controls were 151 women (mean age 54) from the general population without clinical evidence of hand or knee OA. All women were postmenopausal. Serum was assayed by RIA for testosterone, oestradiol, sex hormone binding globulin (SHBG), and dyhydroepiandrosterone sulphate (DHEAS). Because of the differences in mean ages, the results were compared according to equal age groups divided on the basis of tertiles. SHBG was lower in the GOA group, reaching significance in the middle group 53-61 years (58.0 vs 67.9 nmol/l p less than 0.05). Testosterone was slightly higher in GOA women aged under 53. No consistent differences were seen in the older age group or for the other sex steroids. These preliminary data suggest that middle-aged women with GOA have lower circulating SHBG levels. This implies that higher circulating free oestrogens and androgens are present suggesting a role in the aetiopathogenesis of GOA.

Adult↗
PubMed1991

The epidemiology of rheumatic diseases.

This review concentrates on certain areas of current interest in the major rheumatic diseases. In rheumatoid arthritis, there is some epidemiologic evidence that the disease is diminishing in incidence and severity. The possible protective effect on rheumatoid arthritis of the oral contraceptive pill has also attracted attention. There is some evidence that it may act by modifying the disease process. Parity may also be a protective factor in rheumatoid arthritis. Recent twin studies have suggested that the monozygotic concordance rate may be lower than previously believed, suggesting that genetic factors may only account for 20% of the disease. In osteoarthritis, new clinical criteria for the hand, knee, and hip have appeared that require further testing. The finding of a specific mutation of one amino acid of a procollagen II gene in family members with premature osteoarthritis has aroused considerable interest. There has been recent debate on the risk of developing ankylosing spondylitis in the population with HLA B27, although most believe this to be less than 7%. Scleroderma is a rare disease that may be increasing in incidence. One study has suggested the clustering of cases around airports. In the majority of countries, osteoporotic fractures appear to have increased at all ages over the last 30 years, although methods of screening using questionnaires or single bone density measurements are unlikely to be useful as widespread public health measures. The question of estrogen use is increasingly being dominated by the large cardiovascular benefit.

Humans↗
PubMed1991

The relationship between sex steroids and bone mineral content in women soon after the menopause.

Prevention of postmenopausal osteoporosis is now possible with current therapy, if initiated soon after the menopause and continued for at least 10 years. Simple ways of detecting those at risk of subsequent osteoporosis are urgently needed. This study investigated the hypothesis that certain serum sex hormones could predict bone mineral content (BMC) as measured by dual photon densitometry, soon after the menopause. The subjects included 136 healthy white females within 30 months of their last menstrual period with a mean age of 52 years. Of the sex hormones, the adrenal androgen dehydroepiandrosterone sulphate (DHEAS) correlated best with spinal BMC, a relationship which was significant using multiple regression (P = 0.02), although the correlation was weak (r = +0.19). A direct physiological role for DHEAS has yet to be found, despite being present in large quantities in serum, although it may act as a marker for other processes. No association was seen between testosterone, sex hormone binding globulin, oestradiol, oestrone and oestrone sulphate and spinal BMC. No significant correlations with any hormones were seen with femoral BMC. The data suggest that serum sex hormones are not useful markers of current bone mineral status soon after the menopause, although further work is needed to explore the relationship with DHEAS.

Absorptiometry, Photon↗