Diagnosis of pneumonitis in immunocompromised patients by open lung biopsy.

The records of 59 immunocompromised patients with fever and pulmonary infiltrates who underwent open lung biopsy, were reviewed. A specific diagnosis was made by lung biopsy in 49 (83%) patients, and in 32 instances (54%) the diagnosis was a treatable infection. Only two (3.4%) false-negative biopsies occurred. Transplant recipients were more likely to have a specific, treatable pneumonia (74%) than patients with a reticuloendothelial malignancy (42%, P less than 0.05). This was due to a greater frequency of bacterial pneumonias, primarily due to Legionella, in transplant recipients (P less than 0.01). However, obtaining a specific diagnosis by lung biopsy did not appear to improve outcome. Seventeen of 32 (53%) patients with treatable infections survived, compared to 8 of 16 (50%) with specific, but untreatable, diagnosis and 6 of 11 (55%) with nondiagnostic biopsies. Advanced age and a low platelet count were predictive of death in both transplant recipients and patients with leukemia and lymphoma (P less than 0.05); a high serum creatinine was an additional predictor in renal transplant recipients.

Viral enhancement of nasal colonization with Haemophilus influenzae type b in the infant rat.

Infant rats infected with influenza A virus, Sendai (parainfluenza 1) virus or rat coronavirus were used to determine whether viral infection increases the intensity of nasal colonization with Haemophilus influenzae type b (HIB). Intranasal inoculation of HIB in rats previously infected with each of these viruses resulted in nasal HIB titers at least 100-fold higher than those for controls during the first 2 wk after HIB inoculation, and as much as 10,000-fold higher during the first week. Children with cough, sneezing, or rhinorrhea could be effective disseminators of HIB if they were as heavily and persistently colonized as these virus-infected animals.

The effects of cardiovascular drugs on the defibrillation threshold and the pathological effects on the heart using an automatic implantable defibrillator.

Internal defibrillating leads were implanted in 6 dogs through a left thoracotomy and in 6 pigs through a subxiphoid approach. The effects of digoxin (0.04 mg per kilogram of body weight), procainamide (15 mg per kilogram), and propranolol (0.2 mg per kilogram) on the defibrillation threshold was determined 30 to 60 minutes following intravenous administration. Resultant blood levels were equal to or greater than therapeutic levels. Individually these drugs resulted in no appreciable change in the defibrillation threshold from baseline. Pathological study of the myocardium obtained from 6 dogs that underwent more than two hundred shocks each did not demonstrate any abnormality. The 6 pigs were reliably defibrillated, this indicating that thoracotomy is not required for successful implantation. The automatic implantable defibrillator is not the definitive treatment for recurrent ventricular arrhythmias, but is a practical regimen of therapy for a select group of high-risk, out-of-hospital patients. These observations advance our knowledge of the use of this device and give more assurance for future implantation in this select group of patients.

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.

Lethal meningoencephalitis and septicemia caused by Haemophilus influenzae type f in an adult with multiple myeloma.

A patient with chemotherapy-treated multiple myeloma developed overwhelming sepsis and meningoencephalitis with Haemophilus influenzae type f. Typable H. influenzae other than type b has only rarely been reported as a cause of serious disease in adults. The patient's immunosuppressed status presumably predisposed her to this unusual infection.

Monoclonal rheumatoid factor (IgG lambda) its association with amyloid deposits containing lambda light chains.

A patient with monoclonal IgG lambda rheumatoid factor was observed over a period of four years. During this time, serum level of the monoclonal protein fluctuated around 150 mg/dL and homogeneous lambda light chains were present in the urine. The patient died of squamous-cell carcinoma of the lung and no evidence of multiple myeloma was present at the time of autopsy. However, the patient had systemic amyloidosis that affected primarily the blood vessels in most organs. Both the vascular and parenchymal amyloid deposits stained for lambda light chains by the immunoperoxidase technique. These data support the hypothesis that amyloidogenic monoclonal immunoglobulins may be autoantibodies.

Growth of the Pittsburgh pneumonia agent in animal cell cultures.

Pittsburgh pneumonia agent (Legionella micdadei) grew in monkey, chicken, and human cell cultures. Pittsburgh pneumonia agent grew predominantly in the cytoplasm, resulting in a nonfocal, mild cytopathic effect.

Opportunistic Trichosporon pneumonia. Association with invasive aspergillosis.

Two severely immunocompromised patients suffered extensive pulmonary infection with Trichosporon cutaneum (T beigelii) and Aspergillus species. In one patient, the T cutaneum demonstrated yeast forms in tissue sections. The other patient had T cutaneum fungemia prior to death, and examination of lung tissue demonstrated both yeast and hyphal forms. To our knowledge, these patients are the first described with polymycotic infection involving T cutaneum and Aspergillus species. Trichosporon cutaneum must be added to Candida, Torulopsis, and Cryptococcus species as a cause of visceral opportunistic yeast infection.

Mechanism of potentiation of experimental Haemophilus influenzae type B disease in infant rats by influenza A virus.

Intranasal infection of infant rats by virulent influenza A virus increases the frequency and magnitude of bacteremia induced by subsequent atraumatic intranasal inoculation of Haemophilus influenzae type b (HIb). The mechanism of the "potentiating" effect was studied by histology, by measurement of the frequency and kinetics of bacteremia in rats preinoculated with virus, or a chemical irritant (0.1 N HCl), by comparison of the latter with physically "traumatic" bacterial inoculation, and correlation of these data with nasal HIb titers. Both virus and acid induced significant nasal inflammation which progressed following bacterial inoculation. A period of intranasal proliferation of HIb preceded bacteremia in rats preinoculated with either virus or acid. In contrast, bacteremia occurred almost immediately following physically traumatic bacterial inoculation suggesting that direct intravascular invasion had occurred under those circumstances. Repeated atraumatic inoculation of HIb or HIb followed by growth medium both produced a significantly increased frequently of bacteremia compared to a single inoculation, suggesting that the prolonged presence of large numbers of intranasal HIb was a factor in producing bacteremia and that virus or acid-induced mucosal inflammation may lead to elaboration of growth factors for HIb in nasal tissues.

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.

Legionella micdadei (Pittsburgh pneumonia agent): direct fluoresent-antibody examination of infected human lung tissue and characterization of clinical isolates.

Legionella micdadei (Pittsburgh pneumonia agent) was identified by direct fluorescent-antibody (DFA) examination of lung tissue in six of seven persons diagnosed previously as having L. micdadei pneumonia only by histopathology and in four persons who also had positive cultures of the organism. No cross-reactions occurred with monospecific DFA conjugates prepared against Legionella pneumophila serogroups 1 to 6, Legionella bozemanii, Legionella dumoffii, and Legionella gormanii. One person had L. pneumophila serogroup 6 identified by DFA examination of lung tissue and subsequent culture of stored pulmonary secretions. Characterization of the four strains of L. micdadei revealed specific DFA reactions, bacteriological behavior, and cellular fatty acid composition that allow identification of the organism. DFA testing appears to be a sensitive method for identifying L. micdadei prescent in human lung tissue or cultured on artificial media.

Gastrointestinal and disseminated candidiasis. An experimental model in the immunosuppressed rat.

An experimental model of invasive gastrointestinal (GI) candidiasis was studied in immunosuppressed rats. Normal rats were susceptible to disseminated candidiasis by intravascular inoculation (lethal dose for 50% survival [LD50], 1.6 x 10(6) blastospores). Cyclophosphamide-induced leukopenia decreased the LD50 to 1.2 x 10(4) blastospores. Feeding Candida albicans to rats resulted in low-grade GI colonization of normal rats. The intensity of colonization was increased by treatment with cyclophosphamide and broad-spectrum antibiotics. Only in animals fed Candida and treated with both antibiotics and cyclophosphamide did invasive GI lesions develop. However, hematogenous dissemination occurred in only about 10% of such rats. The addition of cortisone acetate to the treatment regimen increased the frequency of hematogenous dissemination to about 25%. Thus, disseminated candidiasis after invasive GI disease can be produced in the rat after exposure to the same predisposing factors as immunosuppressed human patients in whom the disease develops.

The ultrastructural morphologic features of Pittsburgh pneumonia agent.

The fine structure of "Pittsburgh Pneumonia Agent" (PPA) was studied in infected human lung, guinea pig omentum, yolk sac membrane, Vero cell culture, and after cultivation of the organism on buffered charcoal yeast extract agar. The organism is a prokaryotic cell with the general features of a gram-negative bacillus. PPA is ultrastructurally distinctive because of an unusually thick, electron-dense band present within the periplasmic space adjacent to the outer membrane of the cell wall. This band, presumably a mucopeptide (peptidoglycan) layer, was seen in about 95% of organisms in human lung but less frequently under certain conditions of laboratory infection or cultivation. Future studies are required to determine whether this ultrastructural dimorphism of PPA is related to variation in other properties of this bacterium, eg, gram-variability, acid-fastness, colony morphology, and virulence.

Experimental osteomyelitis due to Staphylococcus aureus or Pseudomonas aeruginosa: a radiographic-pathological correlative analysis.

A previously-described experimental model of bacterial osteomyelitis was used to investigate systematically the sequential radiographic and histopathological changes in the tibias of rabbits infected with either Staphylococcus aureus or Pseudomonas aeruginosa. The radiographic changes induced by both organisms were progressive, increasing in severity from the first to the fourth week after infection. The severity and extent of radiographic changes, especially that of bond destruction, were significantly greater for tibias infected with S. aureus. Histopathologically, staphylococcal disease was a severe, rapidly progressive purulent infection which led to extensive destruction of marrow and cortical bone, formation of sequestra, and frequent extraosseous extension. Disease due to P. aeruginosa was more indolent and less destructive, leading to earlier healing and no extraosseous extension. The sequential radiographic and pathological changes observed with this experimental model closely resemble those described in man and suggest that this model may be useful for future investigations of pathogenesis and therapy.

Pittsburgh pneumonia agent: direct isolation from human lung tissue.

Pittsburgh pneumonia agent (PPA) was recently cultivated from infected egg yold on charcoal yeast extract agar. PPA has now been isolated both from infected egg yolk and human lung tissue on charcoal yeast extract agar and on a new medium, buffered charcoal yeast extract agar. PPA resembles Legionella pneumophila and other Legionella-like organisms in requirements for growth and composition of fatty acids. It differs in genetic relatedness, antigenic composition, and colonial morphology and has distinctive characteristics that allow it to be identified. The name Legionella pittsburgensis species nova is proposed for this organism.