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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 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.

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.

Eight immunosuppressed patients had pneumonia due to Pittsburgh Pneumonia Agent (PPA), a gram-negative, weakly acid-fast bacterium cultivatable only in embryonated eggs and guinea pigs and distinct from Legionella pneumophila. The diagnosis was established by isolation of the agent from lung or visualization of the organism in lung tissue. The clinical presentations, radiographic abnormalities and pathology were not specific. The most consistent feature associated with the disease was the recent institution of daily high-dose corticosteriod therapy in all patients. Five of the eight patients died despite broad-spectrum antibiotic and antituberculous therapy. Anti-microbial activity against PPA was demonstrated for sulfamethoxazole combined with trimethoprim, for rifampin and for erythromycin with an egg-protection assay. Serologic studies with an indirect fluorescent-antibody technic suggested that seroconversion or high titers may be a sensitive test for PPA disease. PPA appears to be a newly recognized cause of life-threatening bacterial pneumonia in immunosupressed patients.

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.

In 11 dogs the bacteriologic and morphologic reaction of arterial prostheses made of expanded polytetrafluoroethylene (Gore-Tex) to an induced Staphylococcus aureus septicemia at time of graft implantation was evaluated and compared to that observed with Dacron grafts in 10 dogs. Graft infection developed in all dogs, manifested by positive blood and graft cultures. Grafts, however, could be clearly classified as either histologically infected or uninfected with a marked difference in the pattern of positive blood cultures. Histologically uninfected grafts in general demonstrated the tissue ingrowth and neointima formation which characterize Gore-Tex despite positive graft culture. The appearance of overt histologic infection was correlated with failure of a neointima to develop. Gore-Tex did not loose its structural integrity despite frank injection. The use of the Gore-Tex in the face of overt infection cannot be supported.

Three "new" pneumonias have recently been recognized which are old diseases whose etiology has only been newly-recognized. Legionella pneumophila (Legionnaires' disease), Pittsburgh Pneumonia Agent (PPA), and Legionella-like Organisms (the Family Legionellaceae) are "rickettsia-like" bacteria which require special media for cultivation. They can each cause nosocomial pneumonia in immunosuppressed patients and all but PPA cause community-acquired pneumonia. The Legionellaceae reside in the environment within water and soil. Diagnosis can be established by morphologic, microbiological, and immunologic analysis of respiratory secretions or lung tissue. It may be confirmed retrospectively by serology. Legionella pneumophila and PPA are susceptible to erythromycin and rifampin; erythromycin is the current drug of choice for treatment of these diseases.

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.

A bacterial strain, tentatively identified as an Actinobacillus species, was found to asymptomatically colonize the pharynx of some rats and to bear cell wall antigens which cross-react with noncapsular antigens of Haemophilus influenzae type b (HIb). The cross-reacting antigens appeared to be a heterogeneous mixture with varying molecular size and charge. The antigenic moieties are probably carbohydrate in nature. Antisera raised with this strain had both immunochemical and biological (bactericidal, opsonizing, and protective against experimental infection) activity against HIb. These findings lend further evidence to the idea that noncapsular antigens are important in the induction of resistance to HIb disease. The findings also raise the possibility of using bacteria which cross-react with noncapsular antigens for immunization against HIb disease in humans through nasopharyngeal or enteric colonization.

Intimal calcific atherosclerosis may lead to diminished organ perfusion, whereas medial calcification (Mönckeberg type) is of no physiologic significance. Thirty-nine excised arteries were studied by correlating specimen radiographs with transverse histologic sections to determine whether intimal and medial calcification could be reliably distinguished by radiographic criteria. The calcification was correctly localized in 92% of the arteries studied. Intimal calcification was usually irregular and patchy, whereas medial calcification was regular and diffuse. In one case, extensive medial calcification obscured intimal disease. Plain radiographs may be a useful way to follow progression, regression and the effects of therapy on vaso-occlusive disease in certain high-risk patients.

A patient had systemic amyloidosis that extensively involved the lungs and breasts. Diffuse parenchymal pulmonary amyloidosis is rare but well described. Involvement of the breast in systemic amyloidosis is, however, most unusual. This patient's amyloidosis was associated with diffuse plasmacytosis and a kappa-chain gammopathy. The plasmacytosis was most prominent in the renal interstitium. Immunoperoxidase staining of the renal infiltrate and breast demonstrated IgG/kappa-staining plasma cells exclusively, suggesting that these cells were a monoclonal proliferation that contributed to the patient's M-protein and possibly to the patient's amyloid deposits.

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.

Secondary involvement of the central nervous system by systemic malignant lymphoma is uncommon, although increasingly recognized. Histologically perivascular, leptomeningeal, and subependymal infiltration by tumor cells is characteristic. Less frequently, single or multiple macroscopic masses resembling other metastatic deposits are found. A patient is presented in whom periventricular and leptomeningeal involvement by systemic histiocytic lymphoma produced prominent symmetric surface oriented enhancement on computed tomography following intravenous infusion of contrast medium. Differential diagnosis is discussed.

To determine the significance of Aspergillus species isolated from sputum or other respiratory secretions with respect to the diagnosis of invasive pulmonary aspergillosis, the clinical records and radiographs of all patients whose respiratory secretion cultures yielded an Aspergillus species between 1972 and 1978 were reviewed. All known predispositions to invasive aspergillosis, e.g., presence of cancer or granulocytopenia, and therapy with corticosteroids, antibiotics, and cytotoxic drugs, were significantly associated with proven or probable invasive pulmonary aspergillosis. Most notable were patients with acute leukemia and granulocytopenia. Prolonged duration of hospitalization between initial isolation (greater than 2 weeks) and multiple isolates (greater than three isolates) were also significantly associated with a high frequency of proven or probable disease. Isolation of A. niger was only rarely associated with proven or probable disease (one of eight patients). The isolation of A. fumigatus and A. flavus from respiratory secretions does not usually represent laboratory contamination and must be interpreted in the light of known predispositions to aspergillosis. In some situations, e.g., granulocytopenic patients with acute leukemia, even a single isolation carries a high likelihood of invasive aspergillosis.

Two hundred and ninety-four isolates of Escherichia coli, including 105 from blood cultures, 94 from stools of hospital inpatients, and 96 from rectal cultures of healthy young adults, were biotyped by using the API-20E system and tested for the presence of K1 antigen. The overall frequency of K1 strains was 14.2% and was similar among the three sources. Forty-eight biotypes were observed, but two-thirds of all isolates, including two-thirds of the K1 strains, belonged to only five biotypes. Among the five commonest biotypes, the distribution of K1 strains was nonrandom, since 23 of the 27 K1 strains belonged to only two biotypes. Analysis of the O and H antigens of K1 strains indicated that this correlation of biotype with K1 antigen was due to a restricted number of serovars ("clones") that were repeatedly isolated from the population studied. These serovas included O18:K1:H7, O1:121:H6 and O16:K1:H6. Although a statistically significant correlation between biotype and K1 antigen was observed, the correlation was not sufficiently great to alow biotyping to be of significant predictive value as a marker for the K1 antigen.

Experimental endogenous endophthalmitis was produced in infant rats by either intranasal or intraperitoneal inoculation with Haemophilus influenzae type b and 5 days of age. The ocular disease occurred in about 50% of bacteremic animals who survived to age 12 days and probably represents metastatic bacterial infection secondary to hematogenous seeding. The lesion was a highly destructive suppurative endophthalmitis that ultimately progressed to panophthalmitis and was followed by organization of the exudate and phthisis bulbi.

The fifth reported patient with primary laryngeal oat cell carcinoma is described. Electron microscopy of tumor cells revealed typical neurosecretory-type granules similar to those described for pulmonary oat cell carcinoma. Analysis of clinical data from all five reported patients revealed that this neoplasm is a virulent one which spreads early and rapidly and kills quickly. Combination chemotherapy and/or radiotherapy, which has significantly prolonged life in patients with oat cell carcinoma of lung, may be indicated as an adjunct to surgery for this rare malignant tumor of the larynx.

A patient with a 17-year course of metastatic lobular carcinoma of the breast is described who developed large numbers of circulating carcinoma cells which were easily detectable in several routine peripheral blood smears shortly before death. This rare complication of carcinoma has been called "carcinocythemia." Carcinocythemia is probably due to widespread infiltration of many bone marrow sites and may also be related to splenectomy, which may impair reticuloendothelial clearance of circulating tumor cells. The differential diagnosis of carcinocythemia from superimposed acute myelogenous leukemia, which can complicate radiotherapy and chemotherapy for the primary tumor, is discussed. Cytomorphology, histochemistry, and electron microscopy of abnormal circulating cells should aid in the distinction of these two processes.

The autopsy findings and antemortem radiographic abnormalities were correlated in 20 patients with invasive pulmonary aspergillosis to define typical radiographic patterns, their progression and anatomic basis. Sixteen (80%) patients had radiographic abnormalities due to aspergillosis. Fifty-nine percent of the specific radiographic abnormalities seen in these patients were caused by anatomic lesions of asperigillosis and 67% of such anatomic lesions were radiographically definable. The most common initial radiographic pattern was a patchy density (single or multifocal) or a well defined nodule. The densities remained stable in half the patients but progressed, over several weeks to either diffuse consolidation or cavitation in the others. Most anatomic lesions were categorized as either nodular ("target") lesions (1-3 cm in diameter) or hemorrhagic infarctions (5-10 cm in diameter), both due to vascular invasion causing thrombosis and ischemic necrosis. Unlike pulmonary candidiasis, which is usually radiographically undetectable, invasive pulmonary asperigillosis frequently caused radiographically visible lesions.

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.

Neonatal gastrointestinal colonization of newborn rats with Escherichia coli 075:K100:H5, cross-reactive with the capsular polysaccharide of Haemophilus influenzae type b, was harmless but failed to stimulated detectable ( greater than 200 ng/ml) serum anticapsular antibodies. Neonatally colonized rats, when challenged at age 13 weeks by intraperitoneal inoculation of H. influenzae b, showed no difference in the frequency, magnitude, or duration of bacteremia or in the postinfection anticapsular antibody response when compared with saline-fed controls. However, neonatally colonized rats challenged at age 4 weeks had a significantly decreased incidence of sustained bacteremia and/or endophthalmitis when compared with controls. This decreased frequency of disease correlated with a significant increase in postinfection serum anticapsular antibodies. Neonatal gastrointestinal colonization with cross-reacting E. coli appears to "prime" the young host to respond to infection with H. influenzae b with an anticapsular antibody response that protects against sustained H. influenzae b bacteremia and its complications.

When Haemophilus influenzae type b was given intranasally to infant rats, a very large dose was required to produce histologic evidence of meningitis in even half of the animals tested; meningitis developed in 16 of 31 rats that received 10(7) viable bacteria at the age of five days. However, when the animals first received influenza virus, the dose of bacteria required to produce meningitis was reduced 100-fold; meningitis occurred in 10 of 21 rats given virus at two days and 10(5) viable bacteria at five days. These results suggest that prior viral infection of the upper respiratory tract may be a factor in the pathogenesis of haemophilus meningitis.

Bactermia due to listeria monocytogenes developed in eight patients who were receiving immunosuppresive medications during a 15 month period at one hospital. Seven survived. Meningitis was documented in only the four who received kidney transplants. Their neurologic signs were minimal, indicating a need to treat any immunosuppressed patient with Listeria bacteremia for meningitis. During this period the incidence of Listeria bactermia in immunosuppressed patients greatly exceeded that previously observed in this hospital or reported elsewhere, but the incidence of infection with other opportunistic agents was not increased. As with previously decreased listeria outbreaks in nonimmunosuppressed patients, no source or mechanism of spread could be identified. Thus, disease due to L. monocytogenes may occur focally among immunosuppressed populations, a pattern which also appears to be emerging for other opportunistic agents. A patient's exposure to different opportunistic agents may be as important as the kind of immunosuppressive therapy he recieves in determining which opportunistic infection he will acquire or even whether any infection will occur.

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.

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.

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.

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.

Infected tissues from four patients with disseminated candidiasis were examined by electron microscopy in order to study the host-parasite relationship at the cellular level. Blastospores and pseudohyphae were capable of invading parenchymal cells in the spleen, liver, myocardium, kidney, and esophageal and rectal mucosa. The Candida cells were typically well preserved despite the autolytic changes in parenchymal cells. Extracellular fungi were often coated with fibrin or associated with capillary thrombi, which suggests that Candida cells synthesize a procoagulant substance. The outer flocular coat of the yeast cell appeared to be partially of host origin since it diminished in thickness when organisms were cultured in media devoid of serum protein. Organisms cultured in vitro were ultrastructurally similar to those that invaded tissue.

The nephrotoxic and cytoproliferative side effects observed in a patient with Streptozotocin-treated, multiple hormone-secreting, pancreatic islet cell carcinoma are described. Streptozotocin induced prolonged partial remission of the patient's multiendocrine syndrome but resulted in progressive azotemia, which was controlled by temporary hemodialysis. A renal biopsy, the first to be reported in detail in such a condition, demonstrated a tubulo-interstitial nephritis and a glomerular alteration consisting of cellular nodules. At autopsy there were numerous bilateral renal cortical spindle cell "tumors" and cellular aggregates in glomeruli. These findings suggest that the tumorigenic effects of Streptozotocin demonstrated in animals may also occur in man.

The age-related acquisition of serum anticapsular and bactericidal antibodies to Haemophilus influenzae type b observed in rats was similar to that of humans. The antigenic source for this "natural" immunity was not identified since neither pharyngeal infection with H. influenzae b nor enteric colonization by cross-reacting bacteria was detected. Infant rats surviving H. influenzae b bacteremia failed to respond immunologically to the capsular polysaccharide. However, surviving rats demonstrated no impairment of immune responsiveness to this antigen after subsequent immunization with live bacteria in adulthood. In passive protection experiments, antibodies directed against the type b capsular polysaccharide represented the major protective specificity. However, a small protective effect of antibodies to noncapsular antigens also appeared to have been demonstrated.

A gram-negative, weakly acid-fast bacillus has been isolated in embryonated eggs and in guineapigs from lung tissue of two renal-transplant recipients with acute purulent pneumonia. Culture of infected lung tissue and subculture of the egg isolate on artificial media, including media for legionnaires' disease bacterium (Legionella pneumophila), failed to produce growth. Ultrastructural analysis showed that the organism is a prokaryote with a cell-wall structure typical of a gram-negative bacillus but different from that of L. pneumophila. In both patients serum antibody to both isolates developed in high titre. In its microbiological, tinctorial, and ultrastructural characteristics this bacterium differs sufficiently from L. pneumophila and other pulmonary pathogens to indicate that it may be a new agent of bacterial pneumonia.

The diagnosis of pulmonary candidiasis can only be made with certainty when tissue invasion by the organism is demonstrated histologically. In order to ascertain whether characteristic radiographic patterns are seen in patients with pulmonary candidiasis, antemortem radiographic abnormalities were correlated with autopsy findings in 25 immunosuppressed patients who had histoinvasive pulmonary candidiasis. Pathological analysis enabled division of patients by route of infection into hematogenous and endobronchial groups, characterized by disseminated nodules and patchy bronchopneumonia, respectively. However, no specific radiographic patterns emerged in either patient group due to the small size of lesions and the high frequency of other pulmonary infections, edema, and hemorrhage. Since the radiographic patterns described for other opportunistic fungi do not appear to apply to this organism, a decision to institute antifungal therapy should not await evolution of radiographic changes.

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.

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.

Thirty-nine patients receiving chemotherapy for acute leukemia had weekly determinations of Candida precipitins by use of counterimmunoelectrophoresis. The only two patients who had proven disseminated candidiasis both had diagnostic (greater than or equal to 1/8) titers. However, most patients with "possible" disseminated candidiasis did not have diagnostic titers. The test's specificity was high (90%), and only one of five patients infected with other fungi had diagnostic titers. However, because there were so few "true positives" in this small series, the relatively small number of "false positives" resulted in a low predictive value for this test. Based on a review of the literature and the authors' experience, the value of this test for patients who have acute leukemia does not appear to be well established.

Transbronchoscopic biopsies of lung (transbronchial) or bronchus (endobronchial) have a high diagnostic of yield when performed by a single expert bronchoscopist or a small group of expert bronchoscopists. This procedure's diagnostic yield was evaluated in a general hospital where biopsies are performed by a diverse group of individuals. One hundred fifty-one consecutive biopsies were reviewed, including 53 transbronchial biopsies and 98 endobronchial biopsies. Only 44% of endobronchial biopsies and 21% of transbronchial biopsies were diagnostic. The diagnostic yield was significantly greater in patients with suspected neoplasms (48%) than in patients with suspected infections (13%). Of 97 patients who ultimately had definitive diagnoses established, 43 (44%) had negative biopsy results, including 36% of those with cancers and 80% of those with infections. Failure to obtain alveolar parenchyma by transbronchial biopsy (probably related to the absence of fluoroscopic control) and failure to obtain multiple tissue fragments during each procedure contributed to the low diagnostic yield. The especially disappointing results of transbronchial biopsy for diagnosis of infection suggest that, in this hospital setting, open lung biopsy may be the procedure of choice when infection is suspected.

A 61 year old woman died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. The adenovirus was serologically distinct from the 33 known human adenovirus serotypes and appears to represent a new human adenovirus. Pathologic and virological findings indicate that the pneumonia was only one manifestation of a disseminated infection, the source of which may have been a latent adenovirus infection preexisting in the donor kidney. The establishment of the etiologic diagnosis in this case, which was complicated by the presence of oculocutaneous and esophageal herpes simplex virus infection as well as focal pulmonary aspergillosis, required coordinated histopathologic and virological investigation. Our findings demonstrate that severe viral infections in transplant recipients are not caused exclusively by members of the herpesvirus group.

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.