The effect of gold salts on substance P levels in rheumatoid arthritis.

The effect of gold salt therapy on substance P immunoreactivity levels in plasma and synovial fluid was studied in 42 patients with rheumatoid arthritis. Decreased levels of synovial fluid substance P, although not statistically significant, were found in rheumatoid patients who were currently receiving gold therapy when compared to either those patients previously treated or to those who never received this therapy. In addition, we found that patients who received more than 1000 mg of gold salts had significantly lower levels of substance P in synovial fluid than those treated with lower doses. Our results, therefore, seem to support the hypothesis that gold salts appear to be slow-acting neurotoxic drugs that significantly decrease the intrasynovial concentrations of substance P, a well-known inflammatory neuropeptide, in arthritis patients.

Neuropeptides and interleukin-6 in human joint inflammation relationship between intraarticular substance P and interleukin-6 concentrations.

Plasma and synovial fluid concentrations of interleukin-6 (IL-6), using an enzyme-linked immunosorbent assay, as well as immunoreactive levels of calcitonin gene-related peptide (CGRP), substance P and vasoactive intestinal peptide (VIP) were measured in 18 patients with rheumatoid arthritis and 20 with osteoarthritis of the knee. The concentrations of IL-6 were elevated in both plasma and synovial fluids from patients with rheumatoid arthritis whereas higher levels of substance P-, CGRP- and VIP-like immunoreactivities were found in the synovial fluid, but not in plasma, from patients with rheumatoid arthritis when compared with those in osteoarthritis. Furthermore, IL-6 and substance P levels in synovial fluid were significantly correlated both in rheumatoid arthritis and osteoarthritis patients. Our data seem to support the idea of an important role shared by neuropeptides and IL-6 in the pathogenesis of human inflammatory joint disease.

Benign familial hyperphosphatasemia: a report of two families and review of the literature.

Benign familial hyperphosphatasemia is a rare biochemical abnormality of hereditary nature, characterized by the presence of persistently elevated levels of serum alkaline phosphatase in several members of the same family, in the absence of disease or any known cause of hyperphosphatasemia. To date, there have been 29 pedigrees reported in the literature. Another two families affected with hyperphosphatasemia, originating in an increase in the bone isoenzyme, are described. The epidemiology, inheritance, isoenzymatic patterns, postulated mechanisms and clinical significance of this entity are discussed.

Scleromyxedema associated with arthritis and myopathy: a case report.

Herein we report a patient with scleromyxedema associated with seronegative polyarthritis and proximal myopathy. The histopathologic and electron microscopic features are described and compared with previously reported patients with documented scleromyxedema and myopathy.

Joint symptoms in relapsing polychondritis.

OBJECTIVE: To study articular symptoms in relapsing polychondritis (RP) and their relationship to other clinical manifestations and prognosis. METHODS: Fourteen patients who met the diagnostic criteria proposed by Damiani and Levine for RP were studied. Clinical symptoms were recorded and laboratory and radiologic examinations were carried out. In one patient a synovial histology was obtained. RESULTS: Twelve patients had joint symptoms affecting the peripheral joints (9), the chondrocostal junctions (5), or both sites together (2). Peripheral arthritis was the most frequent finding, affecting 6 patients, while peripheral arthralgia was the only articular manifestation in 3 patients. The development of joint symptoms (arthralgia, arthritis and costochondritis) was unrelated to the appearance of chondritis at other sites and no correlation was found between articular involvement and age at onset, duration of the disease, number of flares, or severity of the disease, either in terms of the number of organs involved or fatal outcome (p > 0.05). However, when articular symptoms were analysed separately arthritis was associated with a longer duration (50 months vs 30), more affected organs (4.5 vs 3.3) and a poorer prognosis compared with patients with arthralgias alone or chondrocostal symptoms. CONCLUSION: Articular symptoms are common in RP but the presence of peripheral arthritis is associated with widespread disease and a poorer prognosis.

Pneumococcal septic arthritis as the first manifestation of multiple myeloma.

In this paper we report a 47 year old woman with septic arthritis due to Streptococcus pneumoniae. No known predisposing factor was found. After an extensive workup a multiple myeloma was discovered. In our case septic arthritis was the first manifestation of multiple myeloma.

Lymphoscintigraphic study in a case of rheumatoid arthritis-related lymphoedema.

Lymphoedema of the upper limbs is a rare extraarticular manifestation of rheumatoid arthritis (RA). Herein we report a patient with RA who presented two episodes of lymphoedema in the hands and forearms coinciding with flares of polyarthritis. Lymphoscintigraphy showed lymphatic-ectasia. The oedema improved with slow-acting drug treatment.

Osteoarticular infection associated with the human immunodeficiency virus.

An analysis is presented of 20 patients with the human immunodeficiency virus (HIV) infection who were treated for skeletal infection in our hospital. Seventeen cases of septic arthritis and three of osteomyelitis were found. All patients were intravenous drug abusers, 75% were male and all were younger than 40 years old. Eighty-eight percent of the septic arthritis cases were monarticular, the hip joint being the area most commonly affected (29%), and Staphylococcus aureus and Candida albicans were the most frequently isolated agents (60% and 20%, respectively). Gram negative bacteria were not found. No correlation between the number of CD4 lymphocytes, affected joints, isolated microorganism or functional capacity was found. Four of 17 patients with septic arthritis and 2 of 3 with osteomyelitis fulfilled the CDC criteria for the diagnosis of acquired immunodeficiency syndrome (AIDS). All cases except one responded to conventional therapy. We conclude that skeletal infection in HIV-infected patients is more closely associated with the risk-group than with HIV itself.

Leg bone pain syndrome due to cyclosporine in a renal transplant patient.

A leg bone pain syndrome of unclear etiology has been recently described in renal transplant patients receiving cyclosporine A. Herein we report a 54-year-old woman treated with cyclosporine A (CsA), corticosteroids and azathioprine who developed two months after renal transplantation severe symmetric pain with periarticular soft tissue swelling in the knees and metatarsophalangeal joints. Scintigraphy showed periarticular radionuclide activity. Clinical onset was associated with both the high dosage and with the plasma levels of CsA. Symptoms improved when the dosage of CsA was reduced and the plasma levels declined to less than 150 ng/ml.

[Efficacy and safety of nabumetone in the treatment of knee osteoarthritis: a comparative clinical trial versus aceclofenac. Study Group of Nabumetone for Osteoarthritis of the Knee]. / Eficacia y seguridad de la nabumetona en el tratamiento de la gonartrosis: ensayo clínico comparativo con aceclofenaco. Grupo de Estudio de Nabumetona en Artrosis de Rodilla.

BACKGROUND: Non-steroidal antiinflammatory drugs are extensively prescribed for the symptomatic treatment of osteoarthritis (OA). This study compared the efficacy and safety of nabumetone with aceclofenac in patients with active knee osteoarthritis. PATIENTS AND METHODS: Phase IV, multicentre, prospective, open-label, parallel-group, randomized, three-month treatment, clinical trial, of nabumetone (1-2 g once a day) vs aceclofenac (100 mg two times each day). The main efficacy variable was intensity of pain, evaluated on a Visual Analogic Scale (VAS). In addition: Gonarthrosis Severity Index (GSI)-baseline score > 5 and < 17-, patient and physician Global Assessment of OA Activity, patient and physician Global Assessment of OA progression were assessed. Adverse events incidence and severity were assessed. Three study visits were made on a monthly basis. The main statistical analysis was by intention to treat (ITT). RESULTS: In 12 centres 274 patients were recruited (137/group), aged 62.5 +/- 8.4 years, of whom 189 completed the trial (97 nabumetone and 92 aceclofenac). 90% were female, and 83% of the patients had both knees affected. In both groups the intensity of pain at month 3 improved significantly (p < 0.001) with respect to baseline: VAS of the nabumetone group: 6.1 +/- 1.9 to 4.3 +/- 2.8 cm; VAS of the aceclofenac group: 6.1 +/- 1.9 to 4.4 +/- 2.7 cm. There were no significant differences in any of the intergroup comparisons made. 15 nabumetone-treated and 23 aceclofenac-treated patients withdrew from the study due to moderate to severe adverse events. Gastrointestinal adverse events were the reason for withdrawal in 7 nabumetone and 14 aceclofenac-treated patients. CONCLUSIONS: The efficacy and safety of nabumetone are similar to those of aceclofenac in the treatment of knee osteoarthritis.

[Polymorphism of the gene of vitamin D receptor and bone mineral density in postmenopausal women]. / Polimorfismo del gen del receptor de la vitamina D y densidad mineral ósea en mujeres posmenopáusicas.

BACKGROUND: Conflicting results have been reported on the association between restriction fragment length polymorphism at the vitamin D receptor (VDR) gene locus and bone mineral density (BMD). Population differences in environmental factors, such as calcium intake and calcidiol levels which have strong influence in BMD, may alter this association. PATIENTS AND METHODS: We analyzed the Bsml RFLP at the eight introm of the VDR gene in a population sample (n = 204) of postmenopausal Spanish women aged 50-65 years being seen clinically and studied calcium intake (dietetic questionnaire) and biochemical parameters (PTH and calcidiol). In parallel bone densitometry were measured in lumbar spine and proximal femur. RESULTS: We identified low BMD of the proximal femur in the BB group. This effect was not observed at other body locations. The calcium intake was lees than 500 mg/day in 60% of the studied population as calcidiol levels were lower than 10 ng/l in 36% of it. The total group population with normal calcium intake (> 1,000 mg/day) showed higher BMD (proximal femur and spine) than the group with low calcium intake, this variation not being observed in group BB alleles. Interestingly, we observed significant differences in BMD proximal femur between genotype groups BB versus Bb + bb when calcidiol levels were < 10 ng/l. Moreover, within the BB subgroup, those subjects with normal calcidiol levels have higher proximal femur BMD compared with those with low calcidiol levels. CONCLUSIONS: Our results indicate an effect of the VDR genotype on BMD proximal femur which is clearly influenced by calcium intake and calcidiol serum levels.

[Hormonal changes in fertile women with quiescent systemic lupus erythematosus]. / Alteraciones hormonales en mujeres fértiles con lupus eritematoso sistémico quiescente.

The hypophyseal-adrenal-ovarian axis was studied in 29 women of childbearing age with systemic lupus erythematosus, as well as in a control group of 14 healthy women. Hormonal levels were measured on days 7th and 21st of menstrual cycle. Women with systemic lupus erythematosus had not significatively lower testosterone levels, but progesterone and 17-alfa-hydroxiprogesterone levels were markedly lower when compared to controls. These facts suggest a decrease in progesterone levels, which could act as a predisposing factor for lupic disease.

Aceclofenac in comparison to ketoprofen in the treatment of rheumatoid arthritis.

The efficacy and tolerability of aceclofenac, a new non-steroidal anti-inflammatory drug (NSAID) was compared to that of ketoprofen in a multicentre, double-blind, prospective, randomized study of 3-months duration in patients with rheumatoid arthritis. One hundred and sixty-nine patients, aged between 22 and 70 years, were included in the study. Patients were randomly assigned to two treatment groups; either aceclofenac 100 mg b.i.d. (87 patients) or ketoprofen 50 mg t.i.d. (82 patients). A placebo tablet was administered to aceclofenac-treated patients to maintain the double-blind conditions of the study. Patients were examined at 15 days and at 1, 2 and 3 months. Efficacy was assessed by the following clinical parameters: Ritchie index, pain on a visual analogue scale, grip strength, morning stiffness, spontaneous morning pain, pain on movement and nocturnal pain, together with functional capacity. Efficacy was demonstrated for both drugs, with progressive improvement in the main clinical evaluation parameters until the end of the treatment period. This was particularly pronounced at 15 days in the aceclofenac group, with a rapid improvement in the Ritchie index (baseline vs 15 days: P < 0.001). Laboratory analyses performed were all within the normal range for both drugs. Eleven patients in the ketoprofen group abandoned the study because of inefficacy, whilst only 4 patients discontinued the treatment for this reason in the aceclofenac group. Eleven patients in the ketoprofen group and 2 patients in the aceclofenac group withdrew from the study because of adverse events. In summary, this study demonstrated that aceclofenac, a new NSAID, is effective in the symptomatic treatment of RA with a minor number of patient withdrawals because of inefficacy and a better safety profile than ketoprofen.

Histologic changes in rheumatoid synovitis induced by naproxen and methotrexate.

OBJECTIVE: To study the changes in rheumatoid synovitis induced by the nonsteroidal antiinflammatory drug (NSAID), naproxen, and methotrexate (MTX). METHODS: Twelve patients were treated with naproxen, and 11 with MTX and a clinical activity index was measured before and after treatment. A synovial biopsy was taken, on entry into the study and after 73 +/- 43 days in the NSAID group and 145 +/- 35 in the MTX group. Synovial cells bearing CD3, CD4, CD8, CD19, LeuM5 (CD11c), HLA-DR, HLA-DP and CD25 antigens were measured by stereology. RESULTS: Patients treated with MTX showed a reduction in the number of CD3+ (p = 0.01), CD4+ (p = 0.007) and HLA-DR+ (p = 0.01) cells with an improvement in the activity index (p = 0.001). The patients treated with naproxen did not show changes in the activity index or in the synovial infiltrate. CONCLUSION: Our findings support the theory that clinical improvement in rheumatoid synovitis is associated with a significant decrease in the number of T cells infiltrating the synovial membrane.

Familial articular chondrocalcinosis in Spain.

One hundred and one first degree relatives of 35 patients with chondrocalcinosis were examined for the presence of familial disease. Eleven subjects from nine families showed radiological chondrocalcinosis, a prevalence of familial disease of 26%. Two different patterns of disease were noted--the older generation was more commonly affected, and the younger generation and second degree relatives were exempt. Clinical and radiological differences were found between the early and late onset groups, but not between late onset and sporadic forms of chondrocalcinosis. These findings support the suggestion that the true prevalence of familial disease. is underestimated. A dominant, autosomal transmission with variable penetrance is consistent with our findings, which suggests that homozygous patients with familial chondrocalcinosis may present a more severe form of the disease.