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Biomedical subjects

W C Winn

Publications and source records attributed to W C Winn.

At least 37 records · Page 2Linked to original sources

Onset and duration of urinary antigen excretion in Legionnaires disease.

The purposes of this study were to determine whether antigen is excreted by patients with Legionnaires disease early enough after the onset of symptoms to be useful for making therapeutic decisions and whether antigen excretion ends when successful treatment is concluded. Specific antigen was detected in the urine of 14 (88%) of 16 patients with Legionnaires disease during days 1 to 3 of symptoms, 33 (80%) of 41 patients during days 4 to 7, 25 (89%) of 28 patients during days 8 to 14, and 11 of 11 patients after day 14, by solid-phase immunoassays for serogroup 1 Legionella pneumophila antigen. Antigen excretion persisted for 42 days or longer after the onset of treatment in at least 15 patients. The longest documented duration of excretion was 326 days. We conclude that antigen can be detected approximately as often early after symptoms begin as later, allowing meaningful therapeutic decisions to be made, but that prolonged antigen excretion may negate the diagnostic value of urinary antigen detection for relapsing or recurrent L. pneumophila pneumonia.

Antigens, Bacterial↗

Stimulatory effect of Pseudomonas aeruginosa on mucin secretion by the respiratory epithelium.

Cell-free filtrates of broth cultures from 11 of 18 strains of Pseudomonas aeruginosa isolated from patients with cystic fibrosis (CF) (or from patients without CF) increased substantially the secretion of mucin by explants of trachea from guinea pigs and human tracheal tissue obtained at autopsy. The effect was not related to the mucoid nature of the isolates, was not destroyed by heating at 90 degrees C for 30 minutes, and was not dependent on serotype. As P aeruginosa commonly infects the respiratory tracts of persons with CF, elaboration of an extracellular product that stimulates mucin secretion could play a role in the pathogenesis of the disease in the airways.

Animals↗

The kinetics of early inflammatory events during experimental pneumonia due to Legionella pneumophila in guinea pigs.

An animal model of Legionella pneumophila pneumonia was developed to study aerosol infection, pathogenesis, and pulmonary host defense mechanisms. Guinea pigs were exposed in an inhalation facility that limited the aerosol of L pneumophila to the snout. Bronchoalveolar lavage was used to sample airspace cells, secretions, and bacteria during developing infection in 79 exposed animals and 13 uninfected controls. An influx of polymorphonuclear neutrophils followed exponential bacterial growth during the initial three days of infection and coincided with limitation of the increase in bacteria recovered. A macrophage influx occurred at three to five days. Bacteria were eliminated from the lung by 11 days after exposure. Albumin in lavage fluid peaked at two days. Most viable L pneumophila organisms were associated with alveolar macrophages, whereas most of the bacteria associated with polymorphonuclear neutrophils were nonviable. Recruited, and possibly immune, defenses appear to be required for successful resolution of legionella pneumonia.

Animals↗

Rapid diagnosis of Legionnaires' disease by latex agglutination.

We developed a latex agglutination test to detect antigen(s) of serogroup 1 Legionella pneumophila in urine and evaluated its ability to diagnose legionnaires' disease. Antigen was detected in 46, or 70%, of 66 patients with serogroup 1 legionnaires' disease but in none of 51 patients with various bacteremic infections nor 60 with urinary tract infections. One of 50 patients with other pulmonary infections was antigen-positive, an immunosuppressed patient with Pneumocystis carinii infection. Seven other patients infected with P. carinii were negative. When compared with radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) using serial dilutions of a single antigen-containing urine, latex agglutination was 16-fold less sensitive. However, 82% of RIA- or ELISA-positive specimens were positive by latex agglutination. Latex agglutination is simpler and more rapid than ELISA or RIA, and it should prove valuable in situations where ELISA or RIA are unavailable or unaffordable.

Antigens, Bacterial↗

Neuropathologic evaluation of 40 confirmed cases of Legionella pneumonia.

Autopsy examination of the brain was performed in 40 cases of Legionella pneumonia. Thirty-nine of 40 patients had underlying chronic or acute medical problems. Sixteen patients (40%) had neurologic signs or symptoms that were not explained by preexisting disease. CSF was normal in six of seven patients examined; CSF protein content was 66 mg/100 ml in one patient. Neuropathologic examination in all 40 patients demonstrated no lesions attributable to disseminated Legionella pneumophila. Mechanisms other than direct cerebral invasion by the causative organism must be sought to explain the neurologic manifestations of Legionella pneumonia.

Adolescent↗

Protein and antibody in lavage fluid of guinea pigs with Legionella pneumophila pneumonia.

Guinea pigs were infected in an inhalation facility that limited an aerosol of L. pneumophila to the snout, as previously reported in detail (Davis et al., 1982). Individual animals were sacrificed for study either immediately after exposure, at 16 hours, at days one through seven, or at 11 days. Bronchoalveolar lavage was carried out to obtain fluid to study the following: total protein, albumin and immunoglobulin G (IgG) concentrations, and the titer of antibody to L. pneumophila. Antibody also was measured in serum obtained at the time of sacrifice. Concentrations of total protein, albumin, and IgG in lavage fluids peaked 2 days after exposure and correlated with the appearance of maximal numbers of polymorphonuclear cells in the lungs. Presumably, this increased protein resulted from exudation of serum across the alveolar-capillary membrane, which loses its integrity secondary to pneumonia. However, the ratio of IgG/albumin was elevated in animals studied 11 days after exposure even though the concentration of albumin was normal by this time. One possible explanation for this observation is that IgG was being produced in the lung. Antibody in lavage fluid was detected 7, and 11 days post-exposure, and might be important in the recovery of guinea pigs from this infection.

Albumins↗

Rapid diagnosis of Legionnaires' disease by urinary antigen detection. Comparison of ELISA and radioimmunoassay.

An enzyme-linked immunosorbent assay was developed to detect urinary antigen excreted by patients with Legionnaires' disease. Of 47 patients tested, antigen was detected in 39. Of these 39 specimens, 35 gave clearly positive results by visual analysis; four others required spectrophotometric verification of positive results. Antigen was not detected in any of 178 urine specimens from patients with other pulmonary, bacteremic or urinary tract infections after a quick and simple confirmatory test. The assay required more time to perform than a previously described radioimmunoassay but was of equivalent sensitivity and specificity and did not require expensive equipment or contract with radioactive reagents. We conclude that enzyme-linked immunosorbent assay is a rapid, sensitive and specific means for rapidly diagnosing legionnaires' disease that can be performed in clinical laboratories unwilling or unable to use radioisotopes.

Antigens, Bacterial↗

Legionnaires' pneumonia after aerosol exposure in guinea pigs and rats.

We developed an animal model of Legionnaires' pneumonia to permit study of aerosol infection, pathogenesis, and pulmonary host defense mechanisms in this disease. Guinea pigs and rats were exposed in a nose-only inhalation facility for 30 min to an aerosol of Burlington serogroup 1 Legionella pneumophila. Lungs contained 10(3) to 10(4) L. pneumophila immediately after exposure. Both guinea pigs and rats developed pneumonia, with 100% infectivity by microbiologic, histologic, and serologic criteria. Guinea pigs demonstrated illness, fever, and 56% mortality; rats showed little illness and 11% mortality. In both species, diffuse patchy pneumonitis coalesced and consolidated as the disease progressed. Aerosol challenge with 3H-L. pneumophila showed exponential growth of the bacteria in the lungs of both species. Guinea pigs and rats can be infected by aerosol exposure to L. pneumophila to produce a disease that closely simulates human Legionnaires' pneumonia. Rapid initial intrapulmonary growth suggests that resident lung defense mechanisms are quite ineffective against L. pneumophila, and that recruited or immunospecific defenses may be more critical in the outcome of infection. The difference in severity of illness between guinea pigs and rats may be exploited for different experimental designs.

Aerosols↗

Hemodialysis fistula infections caused by Legionella pneumophila.

Legionella pneumophila was found in the infected hemodialysis fistulas of two patients. The first patient developed an infection of the fistula during acute illness with Legionnaires' pneumonia. Legionella organisms were shown to be present in the graft by direct immunofluorescent staining. The second patient developed an infection of the hemodialysis fistula 3 weeks after completing a course of erythromycin therapy for Legionnaires' pneumonia. Legionella organisms were found by direct immunofluorescence in purulent material that was obtained from the graft, and serogroup 1 L. pneumophila was isolated from the pus. The frequency with which the organism causes infection of hemodialysis access sites is unknown. Increased awareness by physicians that L. pneumophila produces extrapulmonary disease may result in more frequent detection of these infections.

Adult↗

Sporadic Legionellaceae pneumonia in renal transplant recipients. A survey of 70 autopsies, 1964 to 1979.

The discovery in recent years of previously unrecognized pathogenic bacteria now classified in the family Legionellaceae raised the possibility that significant but undetected infections from these organisms might have occurred in the past. The known susceptibility of immunosuppressed patients to these organisms led us to examine, by direct immunofluorescence, lung tissue from 70 autopsies of renal transplant recipients. Only two cases were detected, one each due to Legionella bozemanii (WIGA) and L micdadei (Pittsburgh pneumonia gent). The lack of cases in this high-risk population contrasts with recent outbreaks at several other institutions and highlights the focal and frequently nosocomial distribution of these infections. A reservoir for these organisms probably did not exist at the Peter Bent Brigham Hospital, Boston, during the 15-years period of this study.

Adult↗

Rapid diagnosis of Legionnaires' disease.

An enzyme linked immunosorbent assay was developed to detect urinary antigen excreted by patients with Legionnaires' disease. Of 47 patients tested, antigen was detected in 39. Antigen was not detected in any of 178 urine specimens from patients with other pulmonary, bacteremic, or urinary tract infections after performance of a quick and simple confirmatory test. The assay required more time to perform than a previously described radioimmunoassay but was of equivalent sensitivity and specificity and did not require expensive equipment of contact with radioactive reagents. We conclude that enzyme linked immunosorbent assay is a rapid, sensitive, and specific means for rapidly diagnosing Legionnaires' disease which can be performed in clinical laboratories unwilling or unable to use radioisotopes.

Antigens, Bacterial↗

Pneumonic and nonpneumonic forms of legionellosis. The result of a common-source exposure to Legionella pneumophila.

Two male maintenance workers contracted legionellosis while cleaning the interior of a cooling tower contaminated with Legionella pneumophila. In one man severe, life-threatening Legionnaires' disease developed, whereas the other experienced a comparatively mild, self-limiting illness that was consistent with previous descriptions of cases of Pontiac fever. This report represents the first documentation of the development of both of these syndromes following exposure to a common source of the organism. The implications of this observation for the pathogenetic mechanisms that underly the different clinical manifestations of legionellosis are discussed.

Anti-Bacterial Agents↗

Isolation of Clostridium difficile from patients with inactive Crohn's disease.

Based upon studies of patients with inflammatory bowel disease, Clostridium difficile and an associated cytotoxin have been proposed as contributory factors in relapse of disease. These studies have not included a comprehensive search for other bacterial pathogens. Fifty patients with Crohn's disease were investigated to determine if selected enteric pathogens colonize the bowel and if they play a role in the activity of the disease. Clostridium difficile was recovered from 8% of patients, all with inactive disease, and recovery of the organism did not presage relapse. Except for Salmonella species in one asymptomatic patient, no other bacterial pathogens were isolated. It was concluded that Clostridium difficile may be part of the bowel flora of patients with Crohn's disease without relationship to activity of disease.

Adolescent↗

Legionnaires' pneumonia after intratracheal inoculation of guinea pigs and rats.

We have developed a model of legionnaires' pneumonia in guinea pigs and rats. A reproducible population of Legionella pneumophila was obtained in late exponential growth phase and inoculated into the trachea of young animals. Either immunologic or microbiologic evidence of infection was demonstrated in 27 or 28 guinea pigs and 19 of 20 rats that had been inoculated with 10(5) to 10(7) colony-forming units. An acute pneumonia that resembled human legionnaires' disease was produced in both species, and Legionella antigen was closely related to inflammation in the distal air spaces. A fatal illness was produced in guinea pigs, and pneumonia was more extensive than in rats. Extrapulmonary inflammatory lesions, particularly splenic necrosis, were more frequent in guinea pigs than in rats. Each rodent species has potential advantages for testing specific questions and both should be useful for future investigations.

Animals↗

The pathology of the Legionella pneumonias. A review of 74 cases and the literature.

Following the discovery of Legionella pneumophila as the cause of an epidemic of pneumonia at an American Legion convention in Philadelphia, a group of related bacteria were recognized as additional human pathogens. This newly established bacterial genus, Legionella, includes the agents of Legionnaires' disease, Pittsburgh pneumonia, and several related infections. There are many similarities in the pathology of human infection caused by all the Legionella species. All produce a severe confluent lobular or lobar pneumonia, and abscess formation is not uncommon. A leukocytoclastic inflammatory infiltrate of neutrophils and macrophages, "septic" vasculitis of small blood vessels, coagulation necrosis, and focal septal disruption are characteristic but not diagnostic features. The inflammatory response is clearly that of a bacterial pneumonia with a necrotizing component, and does not resemble most mycoplasmal, chlamydial, or viral pneumonias. The bacteria can be demonstrated well by special stains. Acid fastness of Legionella micdadei, the cause of Pittsburgh pneumonia, is a helpful presumptive clue to diagnosis. The bacteria can be presumptively speciated in tissue by direct immunofluorescence. In addition, reliable recovery of the organisms on agar media now allows a specific diagnosis to be made. As a group, these infections are properly referred to as the Legionella pneumonias.

Humans↗

Prototheca wickerhamii--an alga infecting the hand.

This report describes a hand infection caused by an alga. Prototheca wickerhamii. This rare organism presents most often as chronic dermatitis or bursitis of the upper extremity. Routine stains and cultures are easily confused with fungi. Only early, radical excision of the involved structures will effect a cure.

Adolescent↗