Influenza virus vaccination of patients with chronic lung disease.

STUDY OBJECTIVES: To evaluate the safety of, and mucosal and systemic immune responses induced by two influenza virus vaccine regimens in subjects with COPD. DESIGN: Single-center, blinded, randomized, prospective clinical trial evaluating two vaccine regimens. SETTING: Outpatient clinics of St. Louis Department of Veterans Affairs Medical Center. PARTICIPANTS: Volunteers (age range, 42 to 88 years) had preexisting COPD with severe obstruction to airflow on average, were male, and were not receiving immunosuppressive medication. INTERVENTIONS: Twenty-nine volunteers were randomly assigned to receive either bivalent live attenuated influenza A virus vaccine (CAV) or saline solution placebo intranasally. All subjects also received an i.m. injection of trivalent inactivated influenza virus vaccine (TVV) simultaneously. MEASUREMENTS AND RESULTS: Clinical status and pulmonary function measured by spirometry did not change significantly after vaccination. Using hemagglutinins (H1 and H3 HA) which more closely resembled those in CAV, mean levels of anti-HA immunoglobulin A (IgA) antibodies in nasal washings increased significantly after vaccination with CAV and TVV compared to prevaccination, but they did not increase significantly after TVV and intranasal placebo. Mean levels of influenza A virus-stimulated interleukin-2 and -4 produced by peripheral blood mononuclear cells in vitro increased significantly after administration of the combination vaccine regimen and to a lesser extent after TVV and intranasal placebo compared to respective prevaccination levels. The timing of the cytokine response appeared different following CAV and TVV compared to TVV and intranasal placebo. CONCLUSIONS: Intranasally administered CAV was safe when given with i.m. administered TVV and there may be an immunologic advantage to administration of the combination vaccine regimen compared to TVV with intranasal placebo.

Tuberculous and foreign-body granulomatous reactions involving a total knee prosthesis.

This case report describes loosening of a right knee prosthesis and represents the first report of the simultaneous occurrence of 2 granulomatous processes involving a prosthetic joint. Microscopic examination of the tissue revealed areas of foreign-body granulomas and areas of necrotizing granulomas and caseation. Acid-fast bacilli cultures were positive for Mycobacterium tuberculosis. The pathophysiology of implant loosening following an inflammatory reaction to components of prosthetic materials is discussed. Also discussed is the occurrence of infectious complications and rarity of tuberculous infections associated with prosthetic implants.

Rapid drug-susceptibility testing of Mycobacterium tuberculosis.

Three methods for rapidly determining the susceptibility of Mycobacterium Tuberculosis isolates to isoniazid, rifampin, ethambutol, streptomycin, and para-aminosalicylic acid were evaluated in a large-scale, blind study. Two of the methods measured evolution of CO2 from radio-labeled substrate (14CO2), and one method measured incorporation of 3H-uracil into ribonucleic acid. Rapid indirect drug-susceptibility test results for nearly 300 isolates were compared with those obtained using a standard modified proportion technique. The 3H-uracil uptake method proved to be unacceptable. Over-all, the results obtained using the 14CO2 methods and the standard method were similar. In general, there was greater agreement between the 14CO2 and proportion techniques with drug-susceptible strains than with drug-resistant strains. Among drug-resistant strains, both 14CO2 methods were more reliable for determining resistance to rifampin than to other drugs. This study demonstrates that large-scale, blind evaluations of new laboratory procedures are valuable. Our results indicate that methods relying o the enzymatic release of 14CO2 should be further refined and evaluated.

Clindamycin-induced enterocolitis in hamsters.

A lethal enterocolitis was induced in hamsters by oral or parenteral administration of clindamycin in amounts comparable to those used in treatment of humans. The intestinal lesions were characterized histologically as an acute inflammatory reaction with pseudomembrane formation and resembled the lesions seen in humans with antibiotic-induced colitis. Results of quantitative stool cultures showed the numbers of Peptostreptococcus and Corynebacterium decreased in animals with colitis after challenge with 100 mg of clindamycin/kg, while numbers of Escherichia coli, Streptococcus faecalis, and clindamycin-resistant Clostridium sordellii and Clostridium difficile increased. Bacteria were not seen within the intestinal lesions. Viruses were not isolated from hamsters with colitis. Although the pathogenesis of this syndrome is not completely established, the evidence is consistent with the hypothesis that the disease is caused by clostridial toxins and that the production of these toxins by organisms within the intestines is enhanced by the effects of clindamycin upon the bowel flora.

Gastrointestinal side effects of clindamycin and ampicillin therapy.

Hospitalized patients who received clindamycin or ampicillin were evaluated for gastrointestinal side effects for a period of up to six weeks after therapy was discontinued. Of 104 patients receiving clindamycin therapy, 31 (29.8%) developed diarrhea, and two (1.9%) developed pseudomembranous colitis (PMC). Of 138 patients receiving ampicillin, 24 (17.3%) developed diarrhea, and one (0.7%) developed PMC. Diarrhea persisting for three days or more was noted in 13 (12.5%) of the patients receiving clindamycin and in seven (5.1%) of those receiving ampicillin. The tendency to develop diarrhea was positively correlated with serious illness, abdominal or pelvic sepsis, and total dosage of clindamycin. Examination of stools from a patient with PMC that was associated with clindamycin therapy showed a decrease in the number of anaerobic bacteria from the numbers found in stool cultures of normal controls. Those patients who did not develop diarrhea also had fewer anaerobic bacteria and coliform organisms. Lymphocytes from the patient with PMC were hyporeactive to phytohemagglutinin and hyperreactive to clindamycin.