Immunosuppressive activity of concanavalin A.

Two strains of mice (C-57 B] and DBA) were given skin allografts from Swiss ICR/HA mice and were treated with varying doses of concanavalin A; the dosage ranged from only two injections of 25 micrograms during the experiment to daily doses of 1000 micrograms intraperitoneally. Immullosuppression was present at all dosages, the most prolonged and consistent effect being observed at 300 micrograms per day. Grafts survived for 14 to 21 days at this dosage compared to 4 to 9 days for controls.

The cytotoxicity of leukocytes and lymphocytes from patients with rheumatoid arthritis for synovial cells.

Unseparated peripheral blood leukocytes obtained from patients with rheumatoid arthritis (RA) were cytotoxic for synovial cells. The cytotoxic reactions produced by RA leukocytes were more frequent and of greater magnitude than cytotoxicity induced by leukocytes from normal persons and patients with other diseases, primarily connective tissue diseases. Furthermore, the cytotoxic activity of RA leukocytes was greater for RA synovial cells than for nonrheumatoid synovial cells, in contrast to the cytotoxicity of other leukocytes, which did not discriminate between synovial cells according to their origin. Tests with purified lymphocytes showed that the cytotoxicity of unseparated leukocytes directed against RA synovial cells was due to lymphocyte cytotoxicity. These data are consistent with the possibility that sensitized lymphocytes from patients with RA recognize a distinctive antigen present on rheumatoid synovial cells.

Polyarthritis, polyarteritis and hepatitis B.

An association between viral hepatitis and two rheumatic disease syndromes has been observed. Twenty-nine patients manifested a transient polyarthritis, sometimes associated with a rash (Group I). Ten patients were seen with a multisystem disease (Group II). Histologic evidence of arteritis or glomerulonephritis was present in seven of ten patients with multisystem disease. Liver tissue from 18 patients showed morphologic evidence of hepatitis with viral features in 9 of 10 patients in Group I and in 6 of 8 patients in Group II. Hepatitis B surface antigen (HBsAg) and/or antibody to HBsAg were detected in sera of all 39 patients. Abnormal liver functions were present in 36. Twelve Group I patients and 2 Group II patients became jaundiced. Rheumatoid factor was present in sera of seven patients in each group. The third component of complement (C3) was depressed in 13 patients in Group I and 7 patients in Group II. The fourth component of complement (C4) was decreased in 8 of 21 Group I and 3 of 7 Group II patients. Synovial fluid C3 was decreased in 2 of 11 Group I and 1 of 4 Group II patient's fluids. Articular inflammation in patients with transient polyarthritis responded in three to seven days to aspirin, acetominophen and/or bedrest alone and rashes disappeared spontaneously. Patients with multisystem disease generally had a prolonged illness and responded somewhat unpredictably to prednisone or a combination of prednisone and cyclophosphamide.

Early experiences with auranofin in juvenile rheumatoid arthritis.

Pharmacologic management of juvenile rheumatoid arthritis is only one of several modalities necessary for effective control. The stepping stones to proper management include a planned long-range program, physical therapy with swimming, good health habits, and consultation with other health professionals who are part of the management team. Pharmacologic therapy includes nonsteroidal anti-inflammatory drugs initially, occasionally corticosteroids, and slow-acting antirheumatic drugs, including injectable gold when therapeutic response is inadequate. Early experiences with oral gold are reported here. Auranofin (triethylphosphine gold) was administered to 21 patients with juvenile rheumatoid arthritis during a segment I, open ended, open-label, noncontrolled trial designed to establish safety and preliminary efficacy. Initial dosage was 0.1 mg/kg per day; incremental increases to 0.2 mg/kg per day were allowed (with usual increase to 0.15 mg/kg per day). Aspirin (80 mg/kg per day) or tolmetin (20 to 40 mg/kg per day), or naproxen (400 to 600 mg/m2 per day) were allowed as rapidly acting antiinflammatory agents. Stable measurable plasma concentrations of gold were attained in all patients during the study. More than half the patients sustained clinically significant improvement (greater than 25 percent) with regard to the number and severity of joints with swelling, pain on motion, and tenderness. In nine of the 19 patients, the total number of joints with active arthritis decreased by at least 25 percent. All articular disease indices measured indicated improvement of group mean changes between the initial and final visit. Eleven of 16 patients with an elevated erythrocyte sedimentation rate showed decreases of at least 25 percent. The group given higher dosages had a greater proportion of responders in regard to decreases in erythrocyte sedimentation rate (nine of 11 patients). Four of six patients whose serums contained rheumatoid factor showed decreases in the titers. Discontinuation of auranofin was necessary in two patients: one because of headache and one because of hematuria and anemia associated with a severe flare-up of polyarticular disease. The results from this trial reveal sufficient patient improvement to plan a double-blind trial of auranofin in children with juvenile rheumatoid arthritis.

Unilateral leptospiral pneumonia and cold agglutinin disease.

Pneumonia that is unresponsive to appropriate antibiotic therapy suggests an infection due to more unusual or resistant organisms. In this report, a child with unilateral pneumonia, pleural effusion, and anti-I cold hemagglutinin antibodies is presented. The usual causes of this clinical picture were suspected and treated, but the child did not improve. Features of her history suggested a more unusual etiology, and a diagnosis of leptospirosis was made. A brief discussion of leptospiral disease in children is provided.

The expanding spectrum of Bartonella infections: II. Cat-scratch disease.

Recent advancements and developments in molecular biotechnology have allowed more precise reclassification of many microorganisms. With the use of these new taxonomy tools, several organisms previously thought to belong to other genera have been recently described as bartonellae. Of the 11 organisms now described as Bartonella spp., only four have been shown to be pathogenic for humans. Table 1 lists the four Bartonella human pathogens along with the their known epidemiology and the scope and range of disease associated with each. All are now considered to be bacteria and can be grown on blood-enriched agar although primary isolation in some may best be achieved in cell tissue culture. B. bacilliformis infection is limited to certain geographic regions in South America where the only human reservoir and the sandfly vector(s) that spreads the disease reside together. Specific antibiotic treatment is dramatically effective in treating the highly fatal, acute intraerythrocytic hemolytic form of the disease, but their effectiveness in treating the vascular proliferative forms (verruga peruana) or the chronic asymptomatic, bacteremic, carrier state of the disease has not been effective. This disease should remain confined to its present endemic geographic areas in South American unless asymptomatic bacteremic persons from these areas migrate to areas where sandflies and humans exist that are capable of establishing this infection in new endemic areas. B. quintana and B. henselae cause a wide range of clinical diseases in humans, the type and extent of which varies significantly with the immune status of the host. In immunocompetent hosts the pathologic response is granulomatous, suppurative, extracellular and intracellular, generally self-limited and usually unresponsive to antibiotic treatment, even to those drugs to which the organism is shown to be sensitive in vitro. In contrast, in immunocompromised hosts the pathologic response is vasculoproliferative, organisms may be seen intracellularly but they are often seen in abundance in extracellular clumps and infection is usually progressive and fatal unless treated. In these patients clinical response to treatment with drugs that are effective in vitro against these organisms has usually been dramatic. Of these agents those that penetrate cells and are found in high concentrations intracellularly, such as erythromycin, clarithromycin, azithromycin, rifampin, doxycycline and gentamicin, appear to be most effective. These agents not only appear to provide the most dramatic treatment response in patients with BA, BP and PRFB and other manifestations of B. henselae (and B. quintana as well) in immunocompromised persons, they appear to be the most promising agents for treatment of persons with both typical and atypical CSD. Further studies will be necessary to more clearly elucidated the mechanisms responsible for the diverse clinical presentations of infection with these organisms in human hosts relative to their immune status. In addition clarification of the epidemiology of B. elizabethae infections in humans may be helpful in understanding the nature of infection with Bartonella organisms.

Prognosis of children with poststreptococcal reactive arthritis.

Patients with Group A beta-hemolytic streptococcal infection and articular disease who do not fulfill the modified Jones criteria for a diagnosis of acute rheumatic fever (ARF) have been classified as poststreptococcal reactive arthritis/arthralgia. We reviewed the initial clinical characteristics and outcome of 12 poststreptococcal reactive arthritis/arthralgia patients. During the initial episode all had arthritis or arthralgia and a documented streptococcal infection. None had carditis and none received prophylactic antibiotic therapy during an average follow-up of 17 months (range, 6 to 42 months). One patient developed classic ARF with valvulitis 18 months after the initial episode. Two children had later episodes of arthritis and two had at least one additional episode of arthralgia. Poststreptococcal reactive arthritis/arthralgias seems to be part of the disease spectrum of ARF and therefore the use of prophylactic antibiotic therapy to prevent subsequent development of ARF and carditis in these patients should, perhaps, be reconsidered.

Prospective randomized double blind placebo-controlled evaluation of azithromycin for treatment of cat-scratch disease.

OBJECTIVE: To determine the efficacy of azithromycin in the treatment of patients with typical cat-scratch disease. DESIGN: Prospective, randomized, double blind, placebo-controlled clinical trial. SETTING: Large military medical center and its referring clinics. PATIENTS: Active duty military members and their dependents with laboratory-confirmed, clinically typical cat-scratch disease. INTERVENTION: Study participants assigned by randomization to treatment with oral azithromycin or placebo for 5 days. OUTCOME MEASURES: Lymph node volume was calculated using three dimensional ultrasonography at entry and at weekly intervals. The ultrasonographer was blinded to the treatment groups. Endpoint evaluations were predetermined as time in days to 80% resolution of the initial total lymph node volume. RESULTS: Demographic and clinical data showed that the azithromycin and placebo treatment groups were comparable at entry although the placebo group tended to be older. Eighty percent decrease of initial lymph node volume was documented in 7 of 14 azithromycin-treated patients compared with 1 of 15 placebo-treated controls during the first 30 days of observation (P = 0.026). After 30 days there was no significant difference in rate or degree of resolution between the two groups. CONCLUSIONS: Treatment of patients with typical cat-scratch disease with oral azithromycin for five days affords significant clinical benefit as measured by total decrease in lymph node volume within the first month of treatment.

Cerebral vasculitis in an adolescent with juvenile rheumatoid arthritis.

A 16-year-old girl with longstanding polyarticular juvenile rheumatoid arthritis was referred from Chuuk State, Federated States of Micronesia, for evaluation and management of weakness and joint pains. She had a right hemiparesis with central facial weakness, polyarticular arthritis, and a dense cataract of the left eye with phthisis bulbi. Extensive evaluation using magnetic resonance angiography revealed vasculitis of the anterior and middle cerebral arteries. She was treated with "pulse" doses of methylprednisolone intravenously and she improved remarkably. Repeat angiography demonstrated dramatic improvement of the vasculitis. There is a paucity of literature regarding cerebral vasculitis in juvenile rheumatoid arthritis. That literature is reviewed, and our patient is discussed with regard to the few published reports.

Treatment of Candida arthritis with flucytosine and amphotericin B.

A premature infant with disseminated Candida tropicalis infection with arthritis and osteomyelitis is presented. Although the organism was susceptible to amphotericin B, synovial fluid cultures were still positive for yeast after 2 weeks of intravenous amphotericin B therapy. The addition of oral flucytosine (25 mg/kg four times daily) resulted in sterilization of the synovial fluid within 4 days. Simultaneous serum and synovial levels of flucytosine were 47.5 micrograms/ml and 39.6 micrograms/ml, respectively. This is the first documentation in the medical literature of intraarticular levels of flucytosine, and provides further rationale for the use of flucytosine in addition to amphotericin B in patients with Candida arthritis.

Sjögren's syndrome in children.

Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of the lacrimal and salivary glands; it eventually leads to keratoconjunctivitis sicca and xerostomia. The disease usually affects middle-aged women and is second to rheumatoid arthritis as the most commonly diagnosed connective tissue disorder. Surprisingly, only 31 cases have been reported in the pediatric population. The diagnosis should be considered, however, in children with a foreign body sensation in the eyes, chronic dryness of the eyes or mouth, or recurrent salivary gland enlargement. This has prompted us to describe our experience in treating five children with SS at Texas Children's Hospital, Houston. One 5-year-old child with no other evidence of connective tissue disease was diagnosed as having primary SS. The remaining four children either had juvenile rheumatoid arthritis or systemic lupus erythematosus in addition to SS, and the diagnosis of secondary SS was made. Other autoimmune disorders associated with SS include polyarteritis nodosa, scleroderma, and polymyositis. Interestingly, one child with secondary SS and chronic lymphocytic thyroiditis developed papillary carcinoma of the thyroid. Both forms of SS are probably more prevalent than the literature would suggest. Recognition of this fact is important if the immediate complications of corneal damage and severe dental decay are to be prevented. Symptomatic treatment with steroids, eyedrops, artificial saliva, and prophylactic fluoride treatments is available. With an adequate follow-up program the late morbidity associated with SS, such as malignant disease, can be minimized.

Wine as a digestive aid: comparative antimicrobial effects of bismuth salicylate and red and white wine.

OBJECTIVE: To test whether red and white wines are as potent as bismuth salicylate against the bacteria responsible for traveller's diarrhoea to try to explain wine's legendary reputation as a digestive aid. DESIGN: Red and white wine, bismuth salicylate, two solutions containing ethanol (diluted absolute ethanol and tequila), and sterilised water were tested against suspensions of salmonella, shigella, and Escherichia coli to determine relative antibacterial activity. Suspensions of 10(7) colony forming units of shigella, salmonella, and E coli were added to the test solutions and plated on standard nutrient agar at 0, 10, 20, 30, 60, and 120 minutes and 24 hours. Dilutions of wine and bismuth salicylate were then tested with E coli as the test bacterium, and the experiment repeated. MAIN OUTCOME MEASURES: Exposure times necessary for eradication of organisms for the different solutions; decreases in colony counts at the different exposure times for dilutions of wine and bismuth salicylates. RESULTS: Undiluted wine and bismuth salicylate were both effective in reducing the number of viable organisms (by 10(5)-10(6) colony forming units) after 20-30 minutes. Dilutions of wine were much more effective in decreasing colony counts than were similar dilutions of bismuth salicylate. CONCLUSION: The antibacterial property of wine is largely responsible for wine's reputation as a digestive aid.