Fatal disseminated adenovirus infection in a renal transplant recipient.

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.

Listeroisis in immunosuppressed patients. A cluster of eight cases.

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.

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.

The behavior of infected arterial prostheses of expanded polytetrafluoroethylene (Gore-Tex).

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.

Correlation of radiographic and histologic findings in arterial calcification.

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.

Diagnostic yield of transbronchoscopic biopsies.

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.

Diagnostic value of candida precipitins determined by counterimmunoelectrophoresis in patients with acute leukemia: a prospective study.

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.

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.

Small cell anaplastic (oat cell) carcinoma of the larynx: report of a case and review of the literature.

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.

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.

Ultrastructural observations in disseminated candidiasis.

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.

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.

Diffuse parenchymal amyloidosis of lungs and breast. Its association with diffuse plasmacytosis and kappa-chain gammopathy.

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.

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.

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.