Richard L. Myerowitz

Opportunistic Lung Infection Due to Pittsburgh Pneumonia Agent

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.

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 < 0.05). This was due to a greater frequency of bacterial pneumonias, primarily due to Legionella, in transplant recipients (P < 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 < 0.05); a high serum creatinine was an additional predictor in renal transplant recipients.

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.

Pathoradiologic correlation of pulmonary candidiasis in immunosuppressed patients

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.

Carcinocythemia (carcinoma cell leukemia) due to metastatic carcinoma of the breast: report of a case.

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. Cancer 40:3107‐3111, 1977.

Nephrotoxic and cytoproliferative effects of streptozotocin: report of a patient with multiple hormone-secreting islet cell carcinoma.

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 patients 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.

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.

Viral Enhancement of Nasal Colonization with Haemophilus influenzae Type b in the Infant Rat

Summary: 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.

DIFFERENCE IN BEHAVIOR OF INFLUENZA A AND B VIRUSES IN INFANT RATS: VIRAL MULTIPLICATION IN NASAL TURBINATES AND POTENTIATION OF BACTEREMIC INFECTION WITH H. INFLU-ENZAE TYPE B

Previous work by Michaels, Myerowitz and Klaw (J.Infect. Dis. in press) showed that the intranasal dose of H. influenzae type b (HIB) required to produce bacteremia and meningitis in about 50% of infant rats was reduced 100-fold when animals were first given influenza A virus (Port Chalmers strain). Similar results have recently been obtained with A/England and A/Victoria viruses.As a part of a study of virus attenuation, 2 day old rats were given 105-107 egg infective doses (EID) of either A/Victoria (A/V) or B/Hong Kong (B/HK) viruses intranasally. At 5 days of age all rats were given 105-106 colony forming units (cfu) of HIB intranasally. HIB bacteremia was found at 7 days of age in 52/97 rats given A/V virus, but in only 3/49 rats given B/HK virus. Bacteremia was detected in none of 38 control rats.In a single experiment, 2 day old rats were given almost identical doses of virus (105.6 EID of A/V or 105.7 EID of B/HK), but the virus titer in nasal turbinates 48 hours later was over 100 times higher for A/V than for B/HK virus. At 5 days of age rats were given 106 cfu of HIB. Subsequent bacteremia was detected in 4/9 rats given A/V and in none of 11 rats given B/HK.The lower turbinate virus titers and lack of potentiation of HIB infection in rats with influenza B as compared to influenza A virus is consistent with epidemiologic observations suggesting that influenza B is often a mild disease in humans.