Comparison of sulfasalazine and placebo in the treatment of reactive arthritis (Reiter's syndrome). A Department of Veterans Affairs Cooperative Study.

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective in the treatment of reactive arthritis (ReA) that has been unresponsive to nonsteroidal antiinflammatory drug (NSAID) therapy. METHODS: One hundred thirty-four patients with ReA who had failed to respond to NSAIDs were recruited from 19 clinics, randomized (double-blind) to receive either SSZ or placebo, and followed up for 36 weeks. The definition of treatment response was based on joint pain/tenderness and swelling scores and physician and patient global assessments. RESULTS: Longitudinal analysis revealed improvement in the patients taking SSZ compared with those taking placebo, which appeared at 4 weeks and continued through the trial (P = 0.02). At the end of treatment, response rates were 62.3% for SSZ treatment compared with 47.7% for placebo treatment. The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. CONCLUSION: SSZ at a dosage of 2,000 mg/day is well tolerated and effective in patients with chronically active ReA.

Should adult tetanus immunization be given as a single vaccination at age 65? A cost-effectiveness analysis.

OBJECTIVE: To compare three vaccination strategies for the prevention of adult tetanus. Each strategy includes childhood primary immunization and wound prophylaxis, and one of the following: 1) the currently recommended booster every ten years; 2) a single booster at 65 years of age; or 3) no intervention after age 6 except for wound prophylaxis. METHODS: Cost-effectiveness analysis was used to compare the three different strategies. A Markov model, cycled annually from age 5 through age 85, was applied to each strategy to predict the incidence and costs of tetanus for the U.S. adult population. RESULTS: The three strategies have very similar effects on life expectancy but different costs. Expressed incremental to no intervention after childhood primary immunization, the decennial booster strategy is least cost-effective, with a discounted incremental cost-effectiveness ratio of $143,138 per year of life saved compared with $4,527 for the single-booster strategy. Sensitivity analysis demonstrates that the decennial strategy is more effective but more costly over a wide range of model assumptions. CONCLUSIONS: The current policy of recommending tetanus booster vaccinations every ten years is effective but much more costly than a more easily implemented policy that also provides considerable protection against tetanus. The authors recommend forsaking decennial boosters in favor of a policy of including a single booster at age 65 along with other recommended health maintenance maneuvers reserved for that age.

Clinical prediction of Pneumocystis pneumonia.

Pneumocystis carinii pneumonia is often difficult to diagnose in an ambulatory care setting. Previous reports have identified elements of the clinical history, physical examination, and clinical testing that are useful predictors of P carinii pneumonia. We analyzed published data on these predictors and measured them against methodologic standards for clinical prediction rules. Variables with high negative or positive predictive value for P carinii pneumonia, low error rates, or compelling biologic credibility were then selected to develop an untested clinical prediction rule for P carinii pneumonia. We suggest that dyspnea, oral lesions, chest roentgenographic examination, and pulse oximetry may be used to select patients requiring sputum testing and/or bronchoscopy for the diagnosis of P carinii pneumonia. The role of pulse oximetry in the diagnosis of P carinii pneumonia merits further study.

Adult chronic lead intoxication. A clinical review.

A stained-glass artisan with depression and a retired junkyard worker with congestive cardiomyopathy had increased mobilizable body burdens of lead by calcium ethylenediaminetetaacetic acid testing. Although both patients improved with several months of intramuscular chelation therapy, the efficacy of such therapy in chronic lead poisoning is controversial. Recognition of unusual manifestations of chronic lead poisoning may at least interrupt further exposure, even if specific therapy is not undertaken.

Reducing bone lead content by chelation treatment in chronic lead poisoning: an in vivo X-ray fluorescence and bone biopsy study.

A stained-glass artist with longstanding exposure to lead presented with neuropsychiatric symptoms. He was evaluated before and after chelation treatment by the CaNa2 EDTA lead mobilization test, iliac crest bone lead measurement, and in vivo tibial X-ray fluorescence (XRF). The three methods showed a progressive fall in body lead stores during chelation therapy in association with improvement in symptoms and a fall in blood lead and zinc protoporphyrin levels. In vivo tibial XRF is a safe, rapid, and noninvasive technique for detecting excessive body lead burdens. XRF measurement of bone lead content is a practical method for monitoring the efficacy of therapy as well as for establishing the diagnosis.

Ulcerative colitis and steroid-responsive, diffuse interstitial lung disease. A trial of N = 1.

We describe a patient with ulcerative colitis and extracolonic manifestations in whom diffuse interstitial pulmonary disease developed that was responsive to glucocorticoid therapy one year after total proctocolectomy. The patient presented in December 1983 with a subacute course marked by cough and progressive exertional dyspnea, abnormal chest examination results, and a chest roentgenogram that revealed diffuse interstitial and alveolar infiltrates. A transbronchial biopsy specimen revealed a polymorphic interstitial infiltrate, mild interstitial fibrosis without apparent intraluminal fibrosis, and no vasculitis, granulomas, or significant eosinophilic infiltration. Within one week of the initiation of daily high-dose steroid therapy, the patient's symptoms dramatically improved; chest roentgenogram and forced vital capacity (60%) improved at a slower rate. All three measures deteriorated when alternate-day prednisone therapy was started but once again improved until the patient was totally asymptomatic, chest roentgenograms were normal, and forced vital capacity was 80% of the predicted value 2 1/2 years later.

Abnormal bactericidal, metabolic, and lysosomal functions of Chediak-Higashi Syndrome leukocytes.

Phagocytic, antimicrobial, and metabolic functions were studied in leukocytes obtained from three patients with the Chediak-Higashi syndrome (CHS) and compared to normals, individuals, heterozygous for Chediak-Higashi syndrome, and two subjects with chronic granulomatous disease of childhood (CGD). Chediak-Higashi syndrome leukocytes showed normal ingestion of a variety of bacteria, Candida albicans, and polystyrene latex particles. Intracellular destruction was significantly impaired for Staphylococcus aureus, Group D streptococci, and a rough strain of Type II pneumococci over a 2 hr incubation. Killing of Serattia marcescens was consistently delayed at 1 hr whereas that of Escherichia coli and C. albicans appeared normal, unless the incubations were shortened to 20 min. Examination of the rates of killing indicated that the greatest defect occurred in the first 20 min of contact between Chediak-Higashi syndrome cells and bacteria. Separation of Chediak-Higashi syndrome granulocytes from monocytes revealed that the former were most defective in bactericidal activity. After phagocytosis, Chediak-Higashi syndrome granulocytes displayed a normal burst in oxygen consumption and oxidation of glucose-1-(14)C and glucose-6-(14)C and formate-(14)C. Oxidation of glucose-1-(14)C by non-phagocytizing Chediak-Higashi syndrome granulocytes and monocytes averaged 2-3 times normal, whereas glucose-6-(14)C and formate-(14)C oxidation were not significantly increased by resting cells. Iodination of intracellular protein by Chediak-Higashi syndrome leukocytes was significantly increased above normal in both the resting and phagocytizing state. Electron microscopic histochemistry revealed that almost all peroxidase activity was localized to the giant granules in Chediak-Higashi granulocytes, and after bacterial ingestion there was a failure of delivery of peroxidase to many phagosomes. Upon longer incubation more phagosomes acquired peroxidase activity, presumably through a fusion process, although many giant granules remained intact. The contrasting patterns and kinetics of the killing defects and the differing metabolic properties of Chediak-Higashi syndrome and chronic granulomatous disease leukocytes emphasize the pleiomorphic nature of inherited disorders of leukocyte function.