Association of birth weight with osteoporosis and osteoarthritis in adult twins.

OBJECTIVES: Twin studies present a unique opportunity to examine the association of birth weight with adult life phenotypes in a design that naturally accounts for maternal factors and a range of early environmental factors, which might potentially bias the association. In this study, we explored the association of birth weight with osteoporosis (OP) and osteoarthritis (OA), in a large national cohort of female twins. METHODS: Intra-pair differences between the reported birth weight of the twins (n=4008) were examined for an association with: (i) intra-pair differences in bone mineral density (BMD) and bone mineral content (BMC) at the lumbar spine, hip and forearm using linear regression; and (ii) osteoarthritis status in pairs discordant for radiographic disease at the hand, hip and knee using matched logistic regression. The confounding influences of height and weight were taken into account. RESULTS: The mean age of the twins was 47.5+/-12.3 yr. Intra-pair differences in birth weight were significantly associated with BMD at the spine (P=0.047), total hip (P=0.016) and femoral neck (P<0.001), but not at the forearm (P=0.245). These were entirely explained by the birth weight association with height and weight. The associations of intra-pair differences in birth weight and BMC were highly significant (P<0.001) at all sites, but were partly explained by adjustment for adult height and weight. We found no clear association between intra-pair birth weight differences and OA in twins discordant for any of the radiographic OA phenotypes at any site. CONCLUSIONS: Bone mass and especially BMC are highly associated with birth weight. These associations are accounted for mainly by environmental factors that are independent of maternal factors such as gestational age, maternal smoking and nutrition, and are largely mediated by skeletal size and particularly adult height. Birth weight does not appear to be a major influence on the later development of radiographic OA in women.

Bone mineral density of patients with chronic plaque psoriasis.

Reduced bone mineral density (BMD), the major risk factor for osteoporotic fracture, has been linked to palmoplantar pustular psoriasis, but no significant studies have examined BMD in chronic plaque psoriasis (CPP). In this study, in-patients with severe CPP had their BMD measured at the nondominant hip and lumbar spine using dual energy X-ray absorbtiometry. Ten male and 10 female Caucasian patients were recruited, with a mean age of 47 years (range 20--71 years). There were no significant differences in BMD between patients and controls. However, patients with psoriatic arthropathy in addition to CPP had a significantly lower mean lumbar spine Z-score (- 1.16) than those without arthropathy (+1.38, P = 0.015). Neither previous nor current treatment with systemic steroids, retinoids or methotrexate significantly affected BMD. We found no evidence that patients with CPP, despite risk factors, have a significantly low BMD, although the subgroup with joint involvement appear be at significantly higher risk of osteoporosis and may therefore require preventative treatment.

Glucocorticoid effects on myocardial performance in patients with systemic sclerosis.

OBJECTIVE: Myocardial inflammation andfibrosis are common autopsyfindings in systemic sclerosis (SSc) and, although symptomatic cardiac involvement occurs less often, current therapies remain empiric and do not prevent or modify its course. In this open, uncontrolled study we assessed the short-term effects of glucocorticoid administration on myocardial performance in patients with SSc in the absence of clinically overt cardiac disease. METHODS: Resting radionuclide ventriculography with 99mTc was performed before and 20 days after the administration of prednisolone, 20 mg daily, in 32 patients with SSc without clinically evident myocardial dysfunction at rest; 13 and 19 patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), respectively, were studied in parallel as controls. RESULTS: The mean left ventricular ejection fraction (LVEF) value at baseline was 59% in the SSc group; similar values were found for the SLE (61%) and RA (59%) groups. An impaired LVEF (i.e., <50%) was found in 6 patients with SSc and in 1 patient with SLE. Prednisolone administration resulted in a significant percent improvement in the baseline LVEF (mean 18%, p = 0.0001) in the SSc group; this improvement was greater in the patients with diffuse SSc than in those with limited skin disease (27% vs 10%, p = 0.02). The improvement was most prominent in the 6 patients with an initial impaired LVEF No significant improvement was observed in the SLE or RA control groups. The linear trend betveen the individual baseline LVEF values in patients with SSc and their percent changes after treatment (r2 = 0.55, p: 0.00001) showed that the lower the initial LVEF the greater the improvement caused by prednisolone. The degree of LVEF improvement was also associated with the individual erythrocvte sedimentation rate values and serum IgG concentrations at baseline. Prednisolone-induced changes in LVEF were not associated with any changes in blood pressure, heart rate, blood, plasma, or red cell volumes. CONCLUSION: Glucocorticoid administration may improve myocardial performance in some patients with SSc. Although further double-blind controlled studies of the long-term effects are warranted, such treatment may be useful in those patients with SSc and documented low LVEF if they are kept under careful observation for objective improvement.

The genetic contribution to hip joint morphometry and relationship to hip cartilage thickness.

A twin study approach was used to explore the genetic determinants of hip joint morphometry and their relationship to hip cartilage thickness. Our analysis used data on anthropometric characteristics and radiographic features of a group of 222 monozygotic (MZ) and 240 dizygotic (DZ) twins. We confirmed that genetic factors account for most of the variation in minimal joint space (MJS) and acetabular anatomy. This genetic variation was largely due to factors unique to MJS itself and not explained by anthropometric variables or measurements of acetabular morphology. Only a small proportion was shared with genetic factors underlying acetabular shape, mainly the centre edge angle.

The genetic contribution to radiographic hip osteoarthritis in women: results of a classic twin study.

OBJECTIVE: To assess the genetic contribution to radiographic hip osteoarthritis (OA) by measuring the distribution of disease features in monozygotic (MZ) and dizygotic (DZ) twins. METHODS: A population-based, cross-sectional study was conducted of 135 MZ and 277 DZ healthy female twin pairs, 50 years of age and older, who were recruited into the St. Thomas' UK Adult Twin Registry. Pelvic radiographs were read by a single observer who was blinded to the pairing and zygosity of the twins. The films were assessed for overall OA grade using a modification of the Kellgren and Lawrence scheme, and assessed for individual radiographic features. RESULTS: There was evidence of significant familial clustering for grade I and grade II OA changes, with an excess concordance in MZ twins compared with DZ twins, suggesting a genetic effect. The MZ versus DZ excess was also apparent for those classified as having more severe disease, although the number of pairs with these disease features was small. Familial clustering attributable to genetic factors was evident for joint space narrowing of <2.5 mm. Familial, but not genetic, clustering was seen for subchondral sclerosis. The number of pairs concordant for definite osteophytes in the sample was too low to assess this feature alone. These results translate into a significant heritability of 58% for OA overall and 64% for joint space narrowing. The heritability estimates decreased a little when the potential confounding influences of age, body mass index, and hip bone density were taken into account. CONCLUSION: Genetic factors have a significant contribution to OA at the hip in women and account for approximately 60% of the variation in population liability to the disease.

A cotwin control study of the relationship between hip osteoarthritis and bone mineral density.

OBJECTIVE: Previous case-control studies have shown various degrees of inverse relationship between osteoarthritis (OA) and osteoporosis (OP). The aim of this study was to examine the relationship between radiographic hip OA and bone mineral density (BMD) at the affected and contralateral hips, as well as at more distal sites. We also explored the possibility that this association might be confounded by genetic factors. METHODS: Using the discordant twin model to reduce selection bias and adjust for genetic factors, plain pelvic radiographs of white female twins aged >40 years, from the St. Thomas' UK Adult Twin Register, were assessed for radiographic features of hip OA. Overall OA was classified using a 6-point global grading system (Croft). Osteophytes (OPH) and joint space narrowing (JSN) were also examined separately. BMD was measured by dual x-ray absorptiometry at the left hip, lumbar spine, and total body. The association of OA with BMD was assessed using conditional logistic regression. Adjustments were made for body mass index, lifetime physical activity, menopausal status, use of estrogen, and smoking. RESULTS: The analysis included a total of 1,148 women comprising 160 monozygotic and 414 dizygotic twin pairs. The median age of the twins was 53 years (range 40-70). The crude and adjusted odds ratios and 95% confidence intervals for having radiographic features of hip OA were 1.63 (1.06, 2.50) and 1.80 (1.05, 3.12), respectively, per unit difference in standardized BMD of the ipsilateral femoral neck. The presence of OPH, but not JSN, was associated with higher BMD. Twins with hip OPH had 3.5% higher femoral neck BMD than their unaffected cotwins. No clear association was found between hip OA and BMD at the contralateral site, lumbar spine, or total body. CONCLUSION: This twin study confirms the existence of an inverse relationship between OA and OP at the hip. However, the relationship was localized to the OA-affected hip. The generalized and greater increase in BMD in osteoarthritic subjects seen in previous studies of unrelated populations is therefore likely to be due, in part, to genetic factors shared by hip OA and high bone mass. It also suggests that local changes in bone density may be a component of the disease process in hip OA.

QT interval in twins.

QT interval has been determined in 103 monozygotic (MZ) and 198 dizygotic (DZ) female twins. Mean values of corrected QT (QTc) were almost identical for both groups at 413 ms (MZ) and 412 ms (DZ). There was a significant age and environmental effect on QT interval. Heritability explained about 25% of the variation in QT. Further research will show whether any of the genes known to cause Long QT syndrome have any effect on QT interval at the sub-clinical level. Journal of Human Hypertension (2000) 14, 389-390

Ultrastructural pathology of the heart in patients with beta-thalassaemia major.

Patients with beta-thalassaemia major frequently suffer from hypersiderosis which leads to hemochromatosis of major organs such as the heart and liver. Little information exists about the ultrastructural pathology of the human heart in beta-thalassaemia patients. Five Cypriot patients with elevated blood ferritin and intractable heart failure were investigated. Cardiac biopsies from these patients were studied by light and electron microscopy, as well as by X-ray microanalysis. Ultrastructural examination revealed the presence of disrupted myocytes showing loss of myofibers, dense nuclei, and a variable number of pleomorphic electron dense granules. These cytoplasmic granules or siderosomes consisted of iron-containing particles as confirmed by X-ray microanalysis. It is likely that the ultrastructural changes observed in myocytes of patients with beta-thalassaemia are largely due to iron deposition.

Plasma renin activity as a marker of renovascular injury in patients with rheumatoid arthritis.

OBJECTIVES: To assess whether plasma renin activity (PRA) in patients with rheumatoid arthritis (RA) and evidence of renal involvement (microhematuria) can serve as potential marker of renovascular injury. METHODS: PRA was measured at rest and following exercise. All nonsteroidal antiinflammatory drugs or other medications that might affect renin release were stopped at least ten days prior to PRA measurements. PRA was correlated with the number of dysmorphic erythrocytes present in the urine sediment as indicators of glomerular capillary injury (microhematuria). RESULTS: All patients with RA had a higher mean PRA than controls. Moreover, all patients with RA in whom microhematuria was present had a higher PRA than those without microhematuria. Simple and multiple regression analysis revealed a significant correlation between: a) PRA and rheumatoid factor levels; b) rheumatoid factor levels and the number of erythrocytes in the urine sediment; and c) PRA levels and the number of erythrocytes in the urine sediment. CONCLUSIONS: The observations indicate that increased PRA may occur in normotensive patients with RA and no clinical or biochemical evidence of renal involvement. This may reflect activation of the renin-angiotensin system. The positive correlation between enhanced PRA, rheumatoid factor levels and microhematuria in RA patients may indicate inflammatory injury of the glomerular microvasculature involving the juxtaglomerular apparatus.

Cardiac involvement in collagen diseases.

The purpose of this study is to evaluate the early morphological and functional abnormalities of the heart in patients with collagen disease. The study population was free of risk factors for coronary artery disease and without any clinically evident cardiac manifestations. In 62 patients with collagen disease (25 with progressive systemic sclerosis, 19 with systemic lupus erythematosus, 15 with rheumatoid arthritis, three with dermatomyositis) and in 40 healthy subjects an echocardiographic study was performed. Echocardiographic examination from the apical four-chamber view was performed at rest and during the end of a 3 min isometric exercise with handgrip. Global and regional ejection fraction of the left ventricle were calculated. In the group with progressive systemic sclerosis the left ventricular mass index was significantly higher than in the control group (110.78 +/- 48.61 vs 82.18 +/- 28.46 g.m-2) and the ejection fraction (53.61 +/- 7.95%) was the lowest of all groups (control: 61.47 +/- 8.52%, systemic lupus erythematosus: 59.04 +/- 8.58%, rheumatoid arthritis: 62.38 +/- 6.88%). Regional ejection fraction analysis revealed a major dysfunction of the proximal segment of the interventricular septum, in all groups. During isometric exercise, the global and regional ejection fraction did not change significantly, although differences between groups disappeared. In rheumatoid arthritis, mitral and aortic valve leaflet separation appeared to be reduced. In the group with systemic lupus erythematosus, mild abnormalities were noticed, although the mean age and duration of the disease were the smallest compared with the other groups. In conclusion, patients with progressive systemic sclerosis mainly present left ventricular hypertrophy with a reduced ejection fraction while rheumatoid arthritis patients show a predominant valve dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

CPPD crystal deposition disease as a cause of unrecognised pyrexia.

We describe three cases of CPPD crystal deposition disease in elderly patients whose main symptom was fever. Misdiagnosis of such cases is possible because of the similarity of the clinical picture to that of septic fever. The probable mechanisms causing the fever are discussed. There was spectacular improvement in these patients after a high dose of oral colchicine and loperamide and no relapse was observed during the long term administration of colchicine in a conservative dose together with supplementary magnesium.

Coronary restenosis: prospects for solution and new perspectives from a porcine model.

Coronary restenosis, a major unresolved problem for percutaneous coronary revascularization procedures, has thus far been resistant to all therapeutic strategies. In part, ineffective treatment or prevention of coronary restenosis may be due to reliance on a conceptualization of the restenosis process that incompletely reflects the pathophysiologic factors associated with neointimal formation after arterial injury. In a porcine coronary restenosis model, three stages of neointimal growth after arterial injury have been identified: an early thrombotic stage, with platelets, fibrin, and erythrocytes; a cellular recruitment stage, with endothelialization and an infiltration by lymphocytes and monocytes; and a proliferative stage, in which smooth muscle cells migrate into and proliferate within the fibrin-rich degenerating thrombus. Evaluation of basic mechanisms responsible for neointimal formation has been possible with this model. In particular, a direct relationship exists between the depth of arterial injury and subsequent neointimal thickness. This relationship can be used for investigating the efficacy of new therapies. Treatment strategies for restenosis should be directed toward interference with the cellular or humoral events that lead to neointimal formation, with the specific goal of decreasing the neointimal volume. These strategies may include delivery of drugs to the site of arterial injury to limit the amount of early mural thrombus or decreasing subsequent cellular recruitment and proliferation as well as synthesis of extracellular matrix.

Small airways dysfunction in systemic sclerosis. A controlled study.

A debate exists regarding the importance of small airways disease in systemic sclerosis, while smoking seems to have a major effect on the exact prevalence. In order to evaluate small airways dysfunction (SAD) in a pure systemic sclerosis population, we performed pulmonary function studies in 31 nonsmoking patients and 31 age- and sex-matched nonsmoking control subjects. Patients' FVC, TLC, and Dco mean values were significantly lower compared with the corresponding values of the controls (p less than 0.05), while there was no difference in MEF25, RV, and RV/TLC. Seven (22.6 percent) of 31 patients and four controls (a nonsignificant difference) had evidence of SAD, namely a maximum expiratory flow at 25 percent of vital capacity (MEF25) less than 60 percent of predicted. Positive correlation (p less than 0.001) was found between MEF25 and FEV1/FVC in the patients. Moreover, no differences were found in abnormal lung function patients with and those without SAD in demographic, clinical, roentgenologic, and serologic features and results of pulmonary function tests. These findings suggest that SAD in our patients is not a characteristic and early manifestation of systemic sclerosis and that, when present, it is not correlated with the severity of the pulmonary involvement in scleroderma.

Cytological evaluation of the effect of Tamoxifen in premenopausal and post-menopausal women with primary breast cancer by analysis of the karyopyknotic indices of vaginal smears.

The influence of Tamoxifen on the vaginal epithelium of 33 premenopausal and 99 post-menopausal women with primary advanced breast cancer was investigated. The karyopyknotic index (KPI) values were assessed before starting therapy and at monthly intervals during therapy with Tamoxifen. A decrease in the KPI in menstruating women and a slight but definite increase in KPI values in post-menopausal women were observed.

Organic brain syndrome with psychosis as an initial manifestation of systemic lupus erythematosus in an elderly woman.

This paper describes a rare case of organic brain syndrome with psychosis and clinically transverse myelopathy, as initial manifestations of systemic lupus erythematosus in an elderly woman. The identification and evaluation of antibodies to ribosome P in the serum and cerebrospinal fluid may be of help in such cases for differential diagnosis. The patient was treated successfully with 30 mg prednisone daily.

Clinical and laboratory parameters in adult diabetics with and without calcific shoulder periarthritis.

The clinical and laboratory parameters of calcific shoulder periarthritis (CSP) were examined in 900 patients with type II diabetes mellitus as well as in 350 age- and sex-matched control subjects. A threefold increased prevalence of CSP in diabetics compared with the control group was associated with the presence of longstanding and poorly controlled diabetes, hypercholesterolemia, and hypertriglyceridemia suggesting pronounced diabetic angiopathy, as well as with minor trauma and hypomagnesemia. Aging and serum calcium concentrations were not related to the presence of CSP. Thirty-two percent of diabetics with CSP were symptomatic; 15% of them presented with severe pain and restriction of shoulder movement. These findings confirm a close pathogenetic interrelation between CSP and diabetes mellitus.

Gout and neurological abnormalities associated with cardiomyopathy in a young man.

A 21 year old man with a family history of gout and neurological deficits, developed severe idiopathic congestive cardiomyopathy after a long history of typical gouty attacks and neurological abnormalities. Clinical and laboratory evaluations showed borderline mental retardation, ataxia, sensorineural deafness, marked hyperuricaemia, and excessive uric acid excretion in the presence of impaired renal function. None of the known causes of cardiomyopathy was found. Even though red cell hypoxanthine guanine phosphoribosyltransferase enzyme activity was normal, this case probably represents an inborn error of purine metabolism. The association of cardiomyopathy with gout is very unusual. Previously it has been only once described in a single case.