Anti-inflammatory drugs reduce age-related decreases in brain volume in cognitively normal older adults.

Previous studies have indicated a decreased risk for developing Alzheimer's disease in anti-inflammatory (AI) drug users. Yet few studies have determined whether AI drug use provides a protective effect against normal age-related changes in the brains of older adults. Regional volume changes in gray and white matter were assessed cross-sectionally using optimized voxel-based morphometry in 36 females taking AI drugs as arthritis or pain medication and 36 age- and education-matched female controls. Although mean gray and white matter volume differences between AI drug users and the non-AI group were small, AI drug use interacted with age, such that the non-AI group showed significantly greater age-related volume changes in regions of both gray and white matter compared to the AI drug users. These regions included the superior and medial frontal gyri, middle and inferior temporal gyri, fusiform and parahippocampal gyri, and occipital gray matter as well as temporal, parietal, and midbrain white matter. The results are consistent with the notion that AI drugs provide protection against age-related changes in brain volume. It is possible that inflammation plays a role in volume decreases associated with normal aging, and that suppressing the inflammatory response moderates this decrease.

Excitatory amino acids, TNF-alpha, and chemokine levels in synovial fluids of patients with active arthropathies.

The aim of this study was to assess the synovial fluid (SF) neurotransmitter excitatory amino acid (EAA) levels, including glutamate (Glu) and aspartate (Asp), in the context of SF levels of other amino acids, TNF-alpha and chemokines from patients with active arthropathies. The SF was collected from patients with active rheumatoid arthritis (RA), gout, or osteoarthritis (OA). The SF samples were analysed for levels of neurotransmitters glutamate and aspartate, tumour necrosis factor-alpha (TNF-alpha), Regulated upon Activation Normally T-cell Expressed and Secreted (RANTES), macrophage inhibitory factor-1 alpha (MIP-1alpha) and interleukin 8 (IL-8). SF WBC counts were also determined. Correlations between SF EAA, TNF-alpha and chemokines were determined by the Pearson product-moment correlation. Primary cultures derived from SF from active RA and gout patients were incubated with added l-glutamate, to assess if exposure to Glu could increase TNF-alpha levels. There were significant elevations in SF EAA, SF TNF-alpha and SF RANTES in RA patients compared to gout or OA patients. Significant correlations between SF EAA and SF RANTES, MIP-1alpha and IL-8 levels were seen, and SF EAA and SF TNF-alpha or SF WBC levels approached significance. Addition of exogenous neurotransmitter glutamate significantly increased TNF-alpha levels in primary cell cultures derived from RA and gout patients. The SF neurotransmitter EAA levels significantly correlated to selected SF chemokine levels, in clinically active RA, gout and OA patients, independent of disease. Added Glu resulted in significantly increased TNF-alpha levels in primary synovial cell cultures. These data expand the relationship of SF neurotransmitter EAA levels to SF cytokines and chemokines in patients with clinically active arthritis, and suggest that neurotransmitters Glu and Asp contribute to peripheral inflammatory processes.

Arthroscopic lavage treatment in rheumatoid arthritis of the knee.

OBJECTIVE: To assess the efficacy of outpatient arthroscopic lavage in rheumatoid arthritis (RA) of the knee. METHODS: 9 patients with RA and active synovitis of at least one knee were selected. All patients were taking disease modifying antirheumatic drugs and nonsteroidal antiinflammatory drugs and had failed intraarticular corticosteroid injection of the knee. Using the 1.9 mm office arthroscope and strict sterile technique the affected knee was lavaged with at least 750 cc of normal saline. At the end of the procedure 40 mg triamcinolone acetonide was injected through the arthroscope. Assessment was done at baseline and 4, 8, and 12 weeks after the lavage using a visual analog scale for pain and 50 foot walk time. RESULTS: 8 of the 9 patients showed marked improvement in their pain and walk time. This effect was maintained at least 12 weeks after the procedure. CONCLUSION: Office arthroscopic lavage treatment is beneficial in a selected group of patients. This procedure is simple and well tolerated without major complications, and may be an option when more conservative therapies have failed.

Clinical efficacy and safety of Naprelan versus Naprosyn in the treatment of rheumatoid arthritis.

A double-blind, randomized study compared the efficacy and safety of a controlled-release naproxen sodium formulation (Naprelan, Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania) 1,000 mg once daily; a conventional naproxen formulation (Naprosyn, Syntex Laboratories, Inc., Palo Alto, California) 500 mg BID; and placebo given for 12 weeks to 348 patients with rheumatoid arthritis (RA). This was followed by an open-label study to evaluate the safety of naprelan 1,000 mg once daily for an additional 9 months. In the double-blind phase of this study, the safety and efficacy of Naprelan 1,000 mg once daily were compared with those of Naprosyn 500 mg twice daily and placebo in 348 patients with RA. At the end of 12 weeks of treatment, Naprelan and Naprosyn were numerically superior to placebo in 3 of the 4 primary efficacy variables--physician's global assessment, patient's global assessment, and number of painful joints. Differences between Naprelan and placebo reached statistical significance for the patient's global assessment at Week 12 (Visit 7). Significantly more Naprosyn- than placebo-treated patients had at least 1 severe digestive system adverse event (AE); 1 drug-related AE; or 1 drug-related, digestive-system AE. There was no statistically significant difference in the number of AEs experienced by Naprelan-treated patients compared with those who received placebo. A total of 240 patients enrolled in the Naprelan open-label phase. As would be expected, patients initially treated with placebo showed significant improvement after starting Naprelan. Those initially receiving Naprelan or Naprosyn also maintained their improvement. The AE profile with Naprelan was similar to that reported in the double-blind phase. It was concluded that Naprelan 1,000 mg once daily was as effective as Naprosyn 500 mg BID in the treatment of RA and was particularly effective in relieving pain later in the day. The controlled-release formulation may also offer safety benefits.

Human recombinant IL-2 augments immunoglobulin and induces rheumatoid factor production by rheumatoid arthritis lymphocytes engrafted into severe combined immunodeficient mice.

Recombinant (r) human IL-2 was administered in vivo to improve homing and engraftment of rheumatoid arthritis (RA) patients' peripheral blood mononuclear cells (PBMC) into severe combined immunodeficient (SCID) mice. Human rIL-2 treatment resulted in augmented human Ig production and induced IgM rheumatoid factor (RF) of human origin in SCID-RA chimeras. The increment of human serum IgG in SCID-RA chimeras after IL-2 treatment ranged between 15 and 43% and for IgM between 50 and 98% during 2-8 weeks postengraftment. Human IgM-RF was detectable after 1 to 2 weeks after engraftment and persisted over a period of 10-13 weeks. No RF was produced in SCID mice engrafted with PBMC from healthy individuals with or without exogenous rIL-2 administration. Thus, human rIL-2 expanded autoreactive clones involved in the production of RF in the SCID-RA chimeras. The present study provides a novel approach to establish an in vivo SCID-RA model to study the cellular and molecular mechanisms involved in the production of RF and development of a RA-like lesion.

Ocular manifestations of immunologic and rheumatologic inflammatory disorders.

Exciting new discoveries into the pathophysiological mechanisms of immunologic and inflammatory ocular disease continue. The genetic locus for susceptibility to Behçet's disease and Sjögrens syndrome has been further characterized. Important guidelines for serial slit-lamp examinations for the early detection of iridocyclitis in juvenile rheumatoid arthritis is suggested. In ocular allergy, further investigation of the interaction between mast cell and eosinophil sheds more light on the pathophysiological mechanism of vernal keratoconjunctivitis and vernal corneal ulcers. Unusual manifestations of Behçet's disease, sarcoidosis, scleritis, and Wegener's granulomatosis are reported. A possible pathophysiological mechanism for lacrimal gland destruction in Sjögrens syndrome is presented.

Preliminary study of the tryptase levels in the synovial fluid of patients with inflammatory arthritis.

This study examined levels of tryptase, a specific mast cell product, in synovial fluid. Samples of synovial fluid from eight patients with rheumatoid arthritis and ten with other arthritides were measured in solid-phase immunoradiometric assays. Elevated concentrations of tryptase were present in samples from three patients with rheumatoid arthritis, one with psoriasis, and one with Reiter's syndrome. The data support the theory that mast cell activation is involved in the pathogenesis in some inflammatory joint diseases, but activation does not appear to be disease specific.

Gout masquerading as rheumatoid vasculitis.

A 30-year-old Mexican woman had rash, deep ulcerations of her lower extremities, and debilitating polyarthritis. Her disorder simulated rheumatoid vasculitis, but serum rheumatoid factor was absent. The diagnosis of gout was confirmed by uric acid crystals in joint fluid and skin biopsy specimens and by x-ray crystallography. The age and sex were unusual for a patient with gout, and she had none of the commonly associated metabolic defects. This unique presentation for urate arthropathy needs further study.

Does rheumatoid factor always mean arthritis?

Rheumatoid arthritis is a clinical syndrome, and the diagnosis requires the presence of pain, swelling, and tenderness in the joints. In the absence of these features, identification of rheumatoid factor in the serum is of little use. Because rheumatoid factor is an immune complex, it is a marker of immune activation and, therefore, may be present in the circulation of persons with a variety of inflammatory conditions that stimulate the immune system. Also, 5% of the healthy population have significant titers of rheumatoid factor in their serum.

Salsalate-induced pancytopenia in a patient with systemic lupus erythematosus.

After a patient with a history of systemic lupus erythematosus in remission was given salsalate, all of her hematologic elements, especially leukocytes, profoundly decreased within hours, although the patient was receiving steroids. She had been challenged with salsalate at an earlier date, with a similar but less impressive drop in blood counts. Granulocytotoxic antibodies persisted during this episode in contrast to declining lymphocytotoxic and anti-native DNA antibodies that accompanied a remission of systemic lupus. This is the first case of this kind occurring with salsalate therapy and may have represented preformed antibodies induced by salsalate.

A community-based epidemiologic study of health sequelae of exposure to hydrofluoric acid.

An accident at an oil refinery in Texas City, Texas, released around 40,000 lb of hydrogen fluoride, exposing the community to the highly toxic and corrosive substance. A population-based epidemiologic study was conducted to evaluate the impact of the accident on the health of the community. Exposure assessment was done using a multipronged approach through a door-to-door survey of 10,811 individuals. A symptom survey resulting in 1994 completed interviews was conducted with a stratified random sample selected from the exposure study database. The sampling was balanced with respect to age, gender, and predisposition across the three ordinal exposure categories. The results show a strong dose relationship (P < 10(-4)) between the exposure and symptoms reported following the accident and 2 years later, most notably breathing and eye symptoms. However, substantial improvement in health was reported over the 2-year period regardless of the level of exposure. Problems of recall bias and behavioral sensitization are considered and it is recognized that the study may have overestimated the effect. It is also recognized that the study may not have completely unraveled the relative importance of exposure and host response in health outcome, since the two were probably conflated in the exposure measure. Nevertheless, the independence of predisposition and reported level of exposure, the magnitude of effect and its consistency, the unmistakable dose response, the large sample size, and the mutual corroboration of various findings make it difficult to dismiss the interpretation that the hydrofluoric acid exposure indeed caused health problems in the community that continued for at least 2 years after the accident.

Polymyalgia rheumatica and temporal arteritis. Related conditions with differing therapies.

Polymyalgia rheumatica and temporal arteritis are entities seen chiefly in older adults. Polymyalgia rheumatica is characterized by muscle and joint aches and an elevated erythrocyte sedimentation rate, and it responds rapidly to low-dose corticosteroid therapy. Temporal arteritis is a vasculitic process, the diagnosis of which must be established by invasive procedures. Higher doses of steroids are necessary to treat it, and the potential for steroid-induced side effects is high.

A double-blind, placebo-controlled study of acetylsalicylic acid (ASA) in trained runners.

Acetylsalicylic acid (ASA) is a short-acting oral inhibitor of the cyclooxygenase enzyme. Ingestion of ASA is associated with a decrease in prostaglandins, including those of the E2 series, as well as prostacyclin, and thromboxane. Consumption of therapeutic doses is associated with decreased pain and inflammation and is therefore used in a variety of inflammatory conditions. Platelet aggregation is also inhibited. Because of these observations, and the fact that platelet aggregation has been noted to be altered during exercise, the effects of ASA on exercise tolerance was of interest. We studied 17 healthy male volunteers who regularly ran as a source of exercise. During the study they ingested either 650 mg of ASA or placebo 30 min before running 2 miles (3.2 km). Outcome of the double-blind crossover study was measured by the time required to run a 2-mile distance. No differences between ASA or placebo were noted in the subjects. These data suggest that 650 mg of ASA as a premedication has little effect on exercise performance in normal endurance runners. However, whether ASA may affect pain after exercise or whether other dosage intervals would be more beneficial needs further study.

Deep venous thrombosis in intravenous cocaine abuse mimicking septic arthritis of the shoulder.

We describe two patients with deep venous thrombosis of the upper extremity who initially were thought to have septic arthritis of the shoulder. These patients had a history of recent intravenous cocaine abuse. The diagnosis of deep venous thrombosis should be considered when a patient with a swollen shoulder has an appropriate history.

Giant-cell arteritis in the southern United States. An 11-year retrospective study from the Texas Gulf Coast.

Giant-cell arteritis (GCA) and polymyalgia rheumatica are systemic disorders that reportedly affect primarily white women older than age 50 years. We conducted an 11-year chart review to determine the relative occurrence and pattern of demographic involvement of GCA in the Gulf Coast region of the United States. Of 101,239 computer-coded entries for individual patients aged 40 years or older, 60 charts listed GCA as a differential diagnosis. Twenty-seven patients had temporal GCA; 21 temporal artery biopsy specimens were identified. Two patients had associated systemic GCA (one with aortitis). A striking finding was that 13 of the 27 patients were black women (about 50% of the entire study population). The group with GCA and polymyalgia rheumatica (17 patients) had a significantly higher mean erythrocyte sedimentation rate than the group with "pure" GCA. Jaw claudication and blindness were rare. We concluded that temporal GCA seems relatively uncommon in the Gulf Coast region and in the southern United States as a whole. Furthermore, GCA seems rare in Hispanics (only one patient identified). Nonetheless, this is the first report to document a proportionally high occurrence of GCA in black patients in this part of the country.