A case-control study assessing bone mineral density in severe haemophilia A in the UK.

It has been shown that bone mineral density (BMD) may be lower in patients with haemophilia (PWH). A comparison to control subjects is required to thoroughly assess current BMD in PWH in the UK. The objective of this study was to test the hypothesis that BMD is lower in PWH than in controls, and in patients with more severely affected joints or lower activity levels. In this case-control study, 37 patients with severe haemophilia A were recruited from two haemophilia centres in the UK. A group of 37 age, gender and ethnicity-matched control participants were recruited. All participants had a bone density scan, a musculoskeletal assessment, a blood test for vitamin D and completed a functional activity questionnaire. Of the case group, 5% had osteoporosis and 24% had BMD lower than expected for age. No control participants had osteoporosis, 3% had osteopenia and 14% had BMD lower than expected for age. Ninety one per cent of case participants and 92% of control participants had reduced 25(OH)D levels. Case participants had significantly lower BMD than control participants, and case participants with more severely affected joints, lower activity levels, HIV, history of hepatitis C or lower BMI had significantly lower BMD. Patients with severe haemophilia have a higher risk of low BMD than men without haemophilia. Patients with more severely affected joints and lower activity levels have lower BMD. It remains unclear whether patients with low BMD reached adequate peak bone mass. Low vitamin D may be present in the majority of PWH.

Effect of non-steroidal anti-inflammatory drugs on the human small intestine.

The suggestion that the intestinal mucosa may be abnormally permeable and thus a site of antigen absorption in rheumatoid arthritis was tested by a 51Cr EDTA intestinal permeability test. Twelve patients with rheumatoid arthritis untreated by non-steroidal anti-inflammatory drugs (NSAIDs) had normal test results, while 12 NSAID-treated patients had increased intestinal permeability. Ten volunteers ingested aspirin, ibuprofen and indomethacin 8 and 1 hours before the study. The increased intestinal permeability was proportional to drug potency to inhibit cyclo-oxygenase. Intestinal permeability also increased following an indomethacin suppository, which suggests that the effect is systemically mediated. 111Indium leucocyte scintigrams and faecal collection showed no evidence of intestinal inflammation in 9 patients untreated by NSAIDs. Twenty-nine of 53 NSAID-treated patients showed abnormal localisation of 111indium in the right iliac fossa at 20 hours, and 32 of 49 patients had increased faecal excretion of 111indium. A 99mTc-porphyrin scan suggested that the main site of NSAID-induced intestinal inflammation was the small bowel. NSAIDs are thus shown to disrupt intestinal integrity and long term treatment leads to inflammation of the small intestine.

Evaluation of the safety, tolerability, and efficacy of meloxicam tablets in patients with osteoarthritis.

This 12-week, open-label, multicenter study assessed the safety, tolerability, and efficacy of the tablet formulation of meloxicam 15 mg, a new, nonsteroidal antiinflammatory drug (NSAID), in patients with confirmed osteoarthritis (OA) of the hip or knee. Meloxicam differs from established NSAIDs in its preferential activity against cyclooxygenase type 2 compared with cyclooxygenase type 1. One hundred thirty-nine patients were given meloxicam tablets 15 mg once daily. Data were analyzed using an intent-to-treat analysis. Assessments of global tolerability at the end of the study showed meloxicam tablets to be well or very well tolerated by 83% of patients, with only 4% rating the tablets poorly. This finding was supported by the low incidence of adverse events. Only 11% of patients discontinued therapy due to gastrointestinal adverse events, and no serious gastrointestinal adverse events related to meloxicam 15-mg tablets occurred during treatment. Efficacy results showed significant improvement from baseline, with 41% of patients experiencing mild or no pain by the end of the study. In conclusion, the tablet formulation of meloxicam 15 mg is well tolerated and effective in patients with moderate-to-severe, clinical confirmed OA of the hip or knee.

Churg-Strauss syndrome and granulomatous cholangiopathy.

Churg-Strauss syndrome is a vasculitis that is known to have gastroenterological manifestations. There have been no reports associating it with liver disease. We present a case of this syndrome in a man who was found to develop a co-existent cholangiopathy. It is likely that this represents an associated granulomatous reaction consequent to a hepatic manifestation of the vasculitis.

Association of DRB1 shared epitope genotypes with early mortality in rheumatoid arthritis: results of eighteen years of followup from the early rheumatoid arthritis study.

OBJECTIVE: To determine whether the HLA-DRB1 shared epitope (SE) is associated with early mortality and specific causes of death in rheumatoid arthritis (RA). METHODS: HLA-DRB1 genotyping was carried out on blood samples from 767 patients recruited for the Early RA Study (ERAS), a multicenter, inception cohort study with followup over 18 years. Dates and causes of death (n = 186) were obtained from the Office of National Statistics. The association of HLA-DRB1 alleles with risk of mortality was assessed using Cox proportional hazards regression analyses. Multivariate stepwise models were used to assess the predictive value of HLA-DRB1 genotypes compared with other potential baseline risk factors. RESULTS: The SE was not significantly associated with overall mortality. However, the presence of 2 SE alleles was associated with risk of mortality from ischemic heart disease (hazard ratio [HR] 2.02 [95% confidence interval 1.04-3.94], P = 0.04), and malignancy (HR 2.18 [95% confidence interval 1.17-4.08], P = 0.01). Analysis of specific SE genotypes (corrected for age and sex) revealed that the HLA-DRB1*0101/*0401 and 0404/*0404 genotypes were the strongest predictors of mortality from ischemic heart disease (HR 5.11 and HR 7.55, respectively), and DRB1*0101/*0401 showed a possible interaction with smoking. Male sex, erythrocyte sedimentation rate, and Carstairs Deprivation Index were also predictive, but the Health Assessment Questionnaire score, rheumatoid factor, nodules, and swollen joint counts were not. Mortality due to malignancy was particularly associated with DRB1*0101 genotypes. CONCLUSION: The risk of mortality due to ischemic heart disease or cancer in RA is increased in patients carrying HLA-DRB1 genotypes with particular homozygous and compound heterozygous SE combinations.

Bilateral Avascular Necrosis of the Lunate in a Patient with Severe Raynaud's Phenomenon and Scleroderma.

We report a case of bilateral avascular necrosis of the lunate, Kienböck's disease, occurring in a patient with limited scleroderma and severe Raynaud's phenomenon who had never received corticosteroids. The patient also had bilateral congenital shortening of the ulnar, which can predispose to Kienböck's disease. The avascular necrosis of the lunate occurred during exacerbations of the Raynaud's phenomenon, which suggests that it was precipitated by the vascular changes associated with Raynaud's phenomenon in scleroderma. Avascular necrosis of the carpus should be considered in the differential diagnosis of patients with chronic wrist pain and scleroderma.

Near fatal eosinophilic gastroenteritis responding to oral sodium chromoglycate.

Eosinophilic gastroenteritis (EG) is an uncommon disorder, characterised by cramping abdominal pain, diarrhoea and vomiting and histologically by eosinophilic infiltration of bowel wall. We present a patient who developed EG during the course of a systemic, necrotising vasculitis, who became critically ill after failure of treatment with corticosteroids and cytotoxic drugs and responded only to oral sodium chromoglycate.

The CREST syndrome--successful reduction of pulmonary hypertension by captopril.

A patient with severe pulmonary hypertension due to pulmonary arteriolar obliteration complicating a long standing CREST variant of systemic sclerosis showed improvement in cardiac output and exercise tolerance during treatment with captopril, which was discontinued because of persistent systemic hypotension. It is suggested that captopril would have a useful and possible prophylactic effect early in pulmonary hypertension in systemic sclerosis.

Listeria monocytogenes septic arthritis following intra-articular yttrium-90 therapy.

Listeria monocytogenes is a rare cause of septic arthritis, which usually occurs in a host compromised by systemic illness. Intra-articular irradiation with yttrium-90 is generally free of complication. We report a case of intra-articular sepsis of the knee joint by Listeria monocytogenes acquired under unusual circumstances.

Corneal chrysiasis and clinical improvement with chrysotherapy in rheumatoid arthritis.

The deposition of gold in the cornea-ocular chrysiasis-is a normal event during chrysotherapy. It may reflect tissue deposition of gold and be of value in predicting clinical improvement or toxic reactions. We studied 21 patients with rheumatoid arthritis on chrysotherapy but could find no relationship between the appearance of ocular chrysiasis, clinical improvement, and toxicity.

Systemic lupus erythematosus and abdominal pain.

Abdominal pain is a common symptom in systemic lupus erythematosus. We report two patients with recurrent severe attacks of abdominal pain, often necessitating hospital admission, which were not diagnosed until laparotomy. In one an active arteritis of the mesenteric arteries was seen, with infarction of the jejunum and ileum, and in the second infarction of the ileum with haemorrhage and conglutination of red cells, but no true arteritis.

Gold nephropathy due to auranofin obscured by tolmetin pseudoproteinuria.

A 63-year-old woman with seropositive rheumatoid arthritis was successfully treated with auranofin for 12 months. Heavy proteinuria then developed and the drug was stopped. However, the proteinuria apparently became worse. This was later recognised to be a spurious effect due to the introduction of tolmetin. Renal biopsy showed a type I membranous glomerulonephropathy.

Community support for young physically handicapped people.

This study examined the cost of home and hospital care for individuals who are severely physically handicapped and who may have many years to live. In addition to quantifying the overall level of these services and their costs, factors which might influence the level of service were identified and their use related to the diagnosis, duration and severity of disability, and number of unpaid carers. Costs of health and social service community support increased with severity of disability, and were mostly incurred by individuals with a Barthel score of less than 50 (more severe handicap). Costs, except for those individuals with cerebral palsy, were independent of the number of careers, and for those of school and university age the costs of special educational facilities were significant.

Stimulation of bone marrow erythropoiesis by T lymphocytes of anaemic patients with rheumatoid arthritis.

An inappropriate response of the bone marrow is implicated in the aetiology of the anaemia of chronic disease complicating rheumatoid arthritis. T lymphocyte subsets have been shown to inhibit early erythroid development in vitro in association with some cases of bone marrow failure, and an expanded peripheral blood pool of these cells is reported in rheumatoid arthritis. We have studied the role of peripheral blood T lymphocytes in erythroid bone marrow culture from seven normal volunteers and nine anaemic patients with rheumatoid arthritis and found comparable stimulation of growth in both groups.

Reversible cortical blindness as a complication of rheumatoid arthritis of the cervical spine.

A case is presented in which a patient with rheumatoid damage to the cervical spine causing cervical cord and vertebral artery compression sustained transient cortical blindness with a partial left hemiparesis. Magnetic resonance imaging revealed anterior subluxation of middle cervical vertebrae, separation of the odontoid peg with resultant atlantoaxial subluxation, and proliferative pannus formation. The patient was almost symptom-free after transoral decompression and posterior cervical fusion.

Capital costs of supporting young disabled people at home.

The quality of life of disabled people depends partly on resources accessible to them. In this study, the capital costs of disability are defined and quantified for disabled people aged 16-64 years, inrelation to: their families, the state, the level of disability, medical diagnosis, and income, for 173 people in the Harrow area on Social Services registers of very severe and appreciable handicap. The mean cost of capital equipment and adaptations was 5,700 pounds (inter-quartile range 200 pounds to 6,600 pounds) to individuals and their families, and 4,500 pounds (inter-quartile range 100 pounds to 6,900 pounds) to statutory bodies (1993 prices, based on a 1988 survey). Two-thirds of this was spent on structural alterations, and one-third on aids and equipment, and costs to the individual were not apparently related to income from employment or state allowances. Capital costs of disability acquired in later life were partly ameliorated for some by accrued pensions, and for those disabled earlier in life, costs were often borne by carers and family. High capital outlay, often borne by the family, was reported for those with congenital disorders. The study indicates the need for financial support, and the need to increase suitable available accommodation for disabled people; regular review may help to identify individual requirements and changing needs.