Simultaneous infection with Legionella pneumophila and Pittsburgh pneumonia agent. Clinical features and epidemiologic implications.

Nosocomial pneumonia caused simultaneously by two organisms, Legionella pneumophila and the Pittsburgh pneumonia agent, was documented in seven patients in one institution. In all seven cases, both organisms were demonstrated by isolation from culture or visualization by direct immunofluorescence. Four patients died as a result of pneumonia, including two who received erythromycin therapy. The hospital water distribution system appeared to be the reservoir for both L. pneumophila and Pittsburgh pneumonia agent. These seven cases constituted 26.9 percent and 17.9 percent of the cases of Pittsburgh pneumonia agent and Legionnaires' disease, respectively, at one institution. Given this relatively high incidence of dual infection, it is likely that the mode of transmission for both organisms is identical. Dual infection may account for some cases of antibody response to more than one Legionella species. Historical parallels of the discovery of L. pneumophila and Pittsburgh pneumonia agent are reviewed.

Legionnaires' disease: new clinical perspective from a prospective pneumonia study.

In an attempt to ascertain the incidence of Legionnaires' disease at our hospital, a prospective case-control pneumonia study was conducted for 11 months. Specialized diagnostic tests for Legionella pneumophila, including serologic study, direct immunofluorescent examination, and selective culture, were made routinely available in our hospital. To our surprise, L. pneumophila was the most common cause of pneumonia (22.5 percent) attributable to a single pathogen, followed by Streptococcus pneumoniae (10.6 percent). In 68.8 percent of the cases, Legionnaires' pneumonia was hospital-acquired. In contrast to other investigators, we found that abdominal pain, diarrhea, neurologic signs, abnormal liver function results, hypophosphatemia, and hematuria did not occur significantly more frequently in pneumonia caused by L. pneumophila than in that caused by other microorganisms. However, hyponatremia within five days of onset of pneumonia occurred significantly more frequently in Legionnaires' disease (p less than 0.0001). Since the clinical presentation is nonspecific, specialized laboratory tests are necessary to make the diagnosis. As a result of our experience, we suggest an approach using serologic tests as a screen to determine whether more specialized tests for Legionnaires' disease should be introduced into a hospital without previously recognized cases of Legionnaires' disease.

IgM and IgG antibody response in two immunosuppressed patients with Legionnaires' disease. Evidence of reactivation of latent infection.

Two patients in whom pneumonia due to Legionella pneumophila developed while they were receiving immunosuppressive therapy had serologic evidence of prior infection with the same serogroup of L. pneumophila two and eight months prior to their clinical pneumonia. This suggests that the pneumonia in these patients may have been due to the reactivation of a latent infection, possibly due to their immunosuppressed state. A new enzyme-linked immunosorbent assay (ELISA) was developed to detect IgG and IgM antibodies to L. pneumophila, and the kinetics of these antibody responses were useful diagnostically.

The graft-versus-host reactivity in AG-B/MLR disparate strains of rats.

Inbred strains of rats can currently be classified into eight Ag-B groups. Within an Ag-B group, individual strains generally share identity both the Ag-B histocompatibility antigens and mixed lymphocyte responses. In this report we present data from three strains which are Ag-B and mixed lymphocyte reaction (MLR) disparate: KGH (Ag-B7, MLR-1), MNR (Ag-B4, MLR-5), and B3 (Ag-B3, MLR-4). Popliteal lymph node assays involving these three strains and standard inbred strains demonstrate that the graft-versus-host reaction and MLR reactions in the rat are closely related. Positive graft-versus-host reactions were observed only in strain combinations incompatible for the MLR and were unaffected by differences in their Ag-B histocompatibility antigens. The close association of the MLR and graft-versus-host reaction provides additional evidence that the Ag-B/MLR disparity in these strains is the result of natural genetic recombinations within the major histocompatibility complex.

Eosinophilic cystitis. A study of 16 cases.

The authors describe 16 examples of eosinophilic cystitis. Cases were predominately in older men, and usually were associated with other conditions of the bladder or prostate. In contrast, most of the 21 cases reported in the English language were in women and children who had a low incidence of associated bladder conditions, but often had allergic disorders and eosinophilia. It appears that either bladder injury or allergy predisposes to eosinophilic cystitis. The bladder-injury type probably occurs fairly commonly and can be misdiagnosed both clinically and pathologically. In most of the present series, the clinical diagnosis was carcinoma of the bladder, and some biopsy specimens superficially resembled specimens from cases of nonspecific chronic inflammation. There was muscle necrosis in most examples, and significant replacement fibrosis of muscle in all the latter sometimes masquerading as mucosal fibrosis. Giemsa stain for eosinophils and trichrome stain for muscle fibrosis are helpful diagnostic aids. Also, eosinophilic cystitis appears related to allergic cystitis and interstitial cystitis.

Small renal adenocarcinoma with metastases.

A case of a 9 mm. renal adenocarcinoma with widespread metastases, including multiple osteoblastic metastases, is presented. An extensive clinical investigation to identify a primary lesion in this patient was negative, including prostatic biopsy, serum electrophoresis, bone marrow biopsy, excretory urography, renal arteriography and abdominal computerized axial tomography scan. Examination at autopsy documented a small adenocarcinoma of the right kidney with local capsular invasion and metastases to the lungs, para-aortic lymph nodes and vertebrae. The differential pathologic and clincal features separating renal adenoma from adenocarcinoma are discussed.

Genetic control of the immune response to poly(Glu52Lys33Tyr15) in neonatally thymectomized high and low responder rats.

The immune response to poly (Glu52Lys33Tyr15) is under polygenic control and linked to the major histocompatibility complex of the rat. Aggregation of this antigen with methylated bovine serum albumin (MeBSA) eliminates the expression of genetic control by increasing the response of low responders and decreasing that of high responders. Humoral and cellular aspects of the immune response to both unaggregated and aggregated poly (Glu52Lys33Tyr15) were investigated in neonatally thymectomized high-responder ACI and low-responder F344 rats. T cells are necessary for responses to unaggregated poly (Glu52Lys33Tyr15) since thymectomy significantly decreased numbers of antibody-forming cells and serum antibody levels, and delayed hypersensitivity responses and antigen-induced in vitro proliferation. However, thymectomy had no significant effect on these parameters of immune responsiveness in either ACI or F344 rats immunized with poly (Glu52Lys33Tyr15)/MeBSA. Aggregation also increased IgG production and delayed hypersensitivity and antibody affinity in low responders.

Two new inhibitory activities in blood of mice with delayed hypersensitivity, after challenge with specific antigen.

In addition to the activities associated with migration inhibitory factor and type II interferon, two other inhibitory activities have been found in the sera of mice infected intravenously with BCG and 3 weeks later challenged intravenously with old tuberculin. Growth of three bacteria, Streptococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, and one yeast, Candida albicans, was inhibited in vitro by a factor or factors in the serum. Also, hematopoiesis of mouse bone marrow cells in a soft agar medium was suppressed by the serum.

The avidity of IgM antibody in high and low responder rats.

This study examined IgM antibody produced by highly responding ACI and poorly responding F344 rats follwing immunization with poly(Glu52Lys33Tyr15) or poly(Glu52Lys33Tyr15) aggregated with methylated bovine serum albunim (MeBSA). The ACI rats produced both IgM and IgG plaque-forming cells (PFC) following immunization with either form of antigen. The F344 rats did not respond to unaggregated poly(Glu52Lys33Tyr15), but they produced significant amounts of IgG PFC and extremely small amounts of IgM PFC after immunization with poly(Glu52Lys33Tyr15)/MeBSA. Both high and low responder rats had similar kinetic profiles of IgM antibody production, and this antibody had nearly identical avidity in both strains with no evidence for any maturation in avidity. thus, one of the genetic defects in the antibody response to poly(Glu52Lys33Tyr15) is an inability of the F344 strain to produce large amounts of IgM in response to this antigen.

Microenzyme-linked immunosorbent assay for detection of immunoglobulin G and immunoglobulin M antibodies to Legionella pneumophila.

The microenzyme-linked immunosorbent assay (ELISA) for the detection of immunoglobulin M and G (IgM, IgG) antibodies to Legionella pneumophila serogroup 1 antigens was evaluated. IgM antibodies were measured by both double-sandwich and single-sandwich techniques. These assays were compared with the previously standardized indirect immunofluorescence test in four groups of subjects: (i) pneumonia patients with culture-proven Legionnaires disease with serogroup 1 isolates, (ii) pneumonia patients with serogroup 1 organisms detected by direct immunofluorescence testing of respiratory secretions but without culture confirmation, (iii) pneumonia patients with negative culture and direct immunofluorescence tests, and (iv) healthy hospital employees. In addition, the sensitivity and specificity of the IgG ELISA were evaluated with larger groups of controls and Legionnaires disease patients. The ELISA was more sensitive than the indirect immunofluorescence test. However, it detected antibody rises in pneumonia patients without culture or direct immunofluorescence evidence of L. pneumophila serogroup 1 infection, thereby suggesting that the specificity of the ELISA was slightly lower than that of the indirect immunofluorescence test. The double-sandwich ELISA was a sensitive method for detecting IgM antibodies and, as previously reported, appeared to be free from interference by rheumatoid factor. IgM anti-Legionella antibodies detected by the ELISA appeared earlier and were less persistent than IgG antibodies. In addition, the IgM ELISA was useful in detecting antibodies in necropsy serum samples obtained from patients dying acutely of Legionnaires disease. The data presented show that the ELISA is a reliable method for the detection of specific anti-Legionella antibodies.