Propionibacterium acnes: pathogen in central nervous system shunt infection. Report of three cases including immune complex glomerulonephritis.

Propionibacterium acnes is a pleomorphic gram-positive anaerobic rod usually isolated as a contaminant from skin. We report three cases of P. acnes infection of central nervous system shunts for hydrocephalus. The organism was seen repeatedly on gram stain in a specimen of shunt fluid in all three cases; initially, it was regarded as a contaminant. In addition, two of the patients had precipitins to extracts of their organism. Serum from normal control subjects had no such precipitins. One of the patients had an immune-complex glomerulonephritis--an entity not previously associated with anaerobic organisms. All three patients recovered after removal of the shunt and treatment with antibiotics. P. acnes is a significant pathogen in patients with central nervous system shunts.     

Cellular immune deficiency with autoimmune hemolytic anemia in purine nucleoside phosphorylase deficiency.

Immunologic and metabolic abnormalities were studied in a five year old boy with 0.07 per cent of normal erythrocyte purine nucleoside phosphorylase activity. The clinical course is characterized by severe autoimmune hemolytic anemia, a transient neurologic disorder with tremor and ataxia, and minor infectious illnesses. There is severe lymphopenia with decreased absolute numbers of T and B lymphocytes. Mitogen-stimulated blastogenesis is reduced, but response to allogeneic lymphocytes is normal. A monoclonal IgG protein is present. There is hypouricemia, elevated plasma inosine level, hypouricosuria and an increase in the urinary concentration of inosine and guanosine. The pattern of heterozygote distribution in the patient's family is compatible with an autosomal recessive trait in which heterozygotes are identifiable. In addition, the unusual laboratory and clinical manifestations of this patient illustrate the heterogeneity of the clinical syndrome associated with purine nucleoside phosphorylase deficiency.     

Asymptomatic IgA nephropathy associated with pulmonary hemosiderosis.

A glomerular lesion identical to that of IgA nephropathy was demonstrated unexpectedly in a 17 year old boy who presented with clinical manifestations of pulmonary hemosiderosis and with no evidence of renal disease. This subclinical glomerular lesion would have remained undetected in this patient unless kidney tissue was obtained and examined by immunofluorescence or electron microscopy. It is unknown if the glomerular lesion in this case is causally related to pulmonary hemosiderosis.     

Carcinoid pericarditis

In this case, carcinoid pericarditis with effusion was one of the dominant clinical features. Carcinoid syndrome is considered briefly. The ways in which carcinoid heart disease can manifest itself are reviewed. Finally, it is proposed that carcinoid pericarditis be added to the spectrum of carcinoid heart disease.     

Clindamycin-associated hepatotoxicity

Hepatotoxicity associated with intravenous clindamycin phosphate therapy is reported in a drug abuser cured of staphylococcal endocarditis. Coincident with the administration of large doses of clindamycin, marked hepatic enzyme abnormalities were noted, and liver biopsy showed lobular disruption, pseudogranulomas, hepatocyte necrosis, eosinophilic bodies and mononuclear cell infiltration. Cessation of clindamycin therapy resulted in return of liver enzymes to normal, and a second liver biopsy performed 15 days later showed improvement. Reports of clindamycin-associated hepatic enzyme changes are reviewed; further observation for clindamycin-associated hepatotoxicity is warranted.     

The echocardiogram in left atrial myxoma

A case of left atrial myxoma is described in which the echocardiogram provided the clue to the diagnosis. The mechanisms involved in producing a positive result are discussed. The value of the echocardiogram appears to depend upon echoes from the tumor during diastole which can be detected immediately posterior to the anterior cusp of the mitral valve. In this case the tumor was successfully removed with restoration of the normal pattern of mitral valve movement.     

Plasma inhibitor of glomerular fibrinolysis in the hemolytic-uremic syndrome

To detect an inhibitor of glomerular fibrinolysis, dilutions of human plasma were incubated on microscope slides with two frozen sections of normal human kidney. The slides were studied by the fibrin slide technique. The lysis inhibitory titer was defined as the highest dilution completely inhibiting glomerular fibrinolysis. Of 27 children without renal disease, none had a lysis inhibitory titer greater than 1:2. Defining an elevated lysis inhibitory titer as 1:8 or greater, we found an elevated lysis inhibitory titer in plasma from all 17 children with hemolytic-uremic syndrome. No correlation was found between the lysis inhibitory titer and the hematocrit, white blood cell or platelet counts, serum creatinine level, or levels of the antiplasmins alpha 1-antitrypsin, alpha 2-macroglobulin, C1-esterase inhibitor, or alpha 2-antiplasmin. The inhibitor was found to have a molecular weight of less than 12,000. A close correlation was discovered between the duration of lysis inhibitory titer elevation and the clinical course; removal of the inhibitor from the plasma by peritoneal dialysis was associated with improvement in renal function. Results suggest that the inhibitor may play an important role in the pathogenesis and persistence of glomerular fibrin deposition.     

Rapid diagnosis of Legionnaires' disease by urinary antigen detection: Comparison of ELISA and radioimmunoassay

An enzyme-linked immunosorbent assay was developed to detect urinary antigen excreted by patients with Legionnaires' disease. Of 47 patients tested, antigen was detected in 39. Of these 39 specimens, 35 gave clearly positive results by visual analysis; four others required spectrophotometric verification of positive results. Antigen was not detected in any of 178 urine specimens from patients with other pulmonary, bacteremic or urinary tract infections after a quick and simple confirmatory test. The assay required more time to perform than a previously described radioimmunoassay but was of equivalent sensitivity and specificity and did not require expensive equipment or contact with radioactive reagents. We conclude that enzyme-linked immunosorbent assay is a rapid, sensitive and specific means for rapidly diagnosing Legionnaires' disease that can be performed in clinical laboratories unwilling or unable to use radioisotopes.     

Therapeutic embolization of the pulmonary artery in pulmonary arteriovenous fistula

A 35 year old white man was admitted in January 1976 for further treatment of pulmonary A-V fistula. In 1975, he had dyspnea, cyanosis and clubbing; pulmonary angiogram showed a fistula in the lower lobe of the left lung and one in the upper lobe of the right lung; the arterial oxygen tension (PaO₂) was 54 mm Hg and the calculated intrapulmonary shunt was 25 per cent of the cardiac output; a lobectomy of the left lung was performed. On this admission, dyspnea, cyanosis and clubbing were still present: the PaO₂ was 67 mm Hg and the intrapulmonary shunt 14 per cent. Since it was possible to show angiographically that, by balloon inflation during Swan-Ganz catheterization of the upper lobe of the right lung, the single pulmonary A-V fistula was completely obliterated with correction of the intrapulmonary shunt, mechanical occlusion was attempted as an alternative to further surgery. Through a No. 7 French catheter inserted via a femoral vein into the pulmonary artery of the upper lobe of the right lung and with the help of repeated selective angiography, six mechanical occluding devices (each consisting of a 5 cm segment of steel guidewire with 3 cm wool tails) were placed into the vessels feeding the fistula. Twenty minutes after placement of the last two coils, the fistula was almost totally occluded on angiogram; the PaO₂ was 79 mm Hg and the intrapulmonary shunt was 7 per cent; over the following three weeks, without further manipulation, these returned to normal (91 mm Hg and 4 per cent, respectively). No complications have been noted. The patient has been symptom free during 12 months of close follow-up; results of oxygen studies have remained normal; on chest film the six coils have not changed position. The procedure described here, to our knowledge performed for the first time for correction of pulmonary A-V fistula, should be considered in preference to surgical resection in selected patients with this condition.     

Pulmonary alveolar proteinosis: successful treatment with aerosolized trypsin.

A 37 year old man with pulmonary alveolar proteinosis and severe pulmonary physiologic impairment was treated empirically for 12 months with continuous oxygen, intermittent positive pressure breathing and aerosolized saline solution, heparin and acetylcysteine. Because of progression of disease, he was treated with aerosolized trypsin in a dose of 100,000 U twice daily for six months. This treatment was associated with dramatic symptomatic, chest roentgenographic and pulmonary physiologic improvement that has lasted for two and a half years without remission. The absence of adverse effects of trypsin aerosol allowed its administration in the patient's home. It is suggested that the preferred initial therapy for symptomatic alveolar proteinosis is aerosolized trypsin.     

Left atrial transport function in myocardial infarction. Importance of its booster pump function.

After myocardial infarction (MI), left ventricular (LV) end-diastolic pressure (EDP) is higher than mean pulmonary artery wedge pressure because of powerful atrial contraction. To evaluate the significane of atrial contraction to left ventricular function we studied 10 control (C) patients without cardiac disease and 17 patients from three to six weeks after acute myocardial infarction. Cardiac catheterization with simultaneous left ventricular diastolic pressure (DP) and left ventricular cineangiograms were obtained. Left ventricular volumes and pressure were (mean +/- SD): (SEE ARTICLE). Although left ventricular stroke volume was lower in the patients with myocardial infarction than in the control subjects (46 versus 56 ml/m2), atrial contraction contributed more to left ventricular filling during diastole (which is the same as left ventricular stroke volume) in the patients with myocardial infarction than in the controls (16 versus 10 ml/m2). The average atrial contribution to left ventricular end-diastolic volume was 11.9 per cent (C), 15.4 per cent (MI); to left ventricular end-diastolic pressure 20 per cent (C), 38.7 per cent (MI); and to left ventricular stroke volume 21.7 per cent (C), 35.1 per cent (MI). Atrial contribution to left ventricular stroke volume was 56 per cent in patients with a cardiac index less than or equal to 2.0 liters/min/m2 and 31 per cent in those with a cardiac index greater than 2 liters/min/m2 (p less than 0.01). Atrial contraction contributed 35 per cent to left ventricular stroke volume in patients with normal end-diastolic volume and in those with increased end-diastolic volume and 10 per cent to end-diastolic volume in patients with increased end-diastolic volume (p less than 0.001). In patients with myocardial infarction, atrial contraction made a large contribution to left ventricular filling and stroke volume irrespective of the type of left ventricular functional derangement that was present. The "booster pump" function of the atrium cannot be ignored in assessing left ventricular performance.     

Diagnosis and localization of pheochromocytoma. Detection by measurement of urinary norepinephrine excretion during sleep, plasma norepinephrine concentration and computerized axial tomography (CT-scan).

The feasibility of differentiating patients with pheochromocytoma from other hypertensive patients by measuring urinary excretion rates of norepinephrine during sleep, a period of physiologic suppression of norepinephrine release, was investigated. The mean excretion rates of norepinephrine in 248 normal subjects and in 109 patients with essential hypertension were 1.03 +/- 0.03 and 1.12 +/- 0.06 (SEM) micrograms/hour, respectively, whereas the lowest excretion rate among the six patients with pheochromocytoma was about seven times higher. Plasma norepinephrine concentration in patients with pheochromocytoma was also consistently above the range observed in both normotensive and hypertensive subjects. CT scan correctly identified the same tumors visualized by selective arteriography. It is suggested that the usefulness of these approaches will provide simpler means of screening and detecting pheochromocytoma.     

Increase in plasma norepinephrine during prazosin therapy for chronic congestive heart failure

To investigate the mechanism of pharmacodynamic tolerance reported to occur during prazosin therapy of chronic congestive heart failure, we measured plasma norepinephrine, plasma epinephrine, plasma renin activity (PRA) and plasma aldosterone, as well as hemodynamics in eight patients with chronic congestive heart failure, functional class III and IV (NYHA), before and during 10 weeks of prazosin therapy.Initially, prazosin therapy produced significant hemodynamic improvement, but no significant changes were noted in norepinephrine, epinephrine, plasma renin activity or aldosterone. During ambulatory therapy, fluid retention developed in four patients, and three of them had symptoms or clinical evidence of congestive heart failure for which they required an increase in diuretic or prazosin therapy. Plasma norepinephrine levels for the whole group were signficantly higher after four weeks of therapy (p < 0.01). Repeat inpatient studies after 10 weeks showed a persistent hemodynamic response to prazosin in seven patients. One patient demonstrated complete hemodynamic tolerance whereas three others showed partial tolerance. In these four patients the cardiac output increased only to 3.78 ± 1.17 liters/min compared to 5.04 ± 2.11 liters/min during initial prazosin therapy. Plasma norepinephrine increased further and levels were significantly higher for the whole group than before prazosin therapy (p < 0.05). No significant changes in epinephrine, plasma renin activity or aldosterone were demonstrated.This increase in plasma norepinephrine suggests that the sympathetic nervous system could be involved in the pharmacodynamic tolerance to prazosin therapy in congestive heart failure. Further studies are necessary to extend these results.     

A syndrome of congenital cardiomyopathy with mitral regurgitation, complete heart block and atrial arrhythmia

A distinctive syndrome of cardiomyopathy with mitral regurgitation, complete heart block and atrial arrhythmia was noted in four male patients aged 19 to 49 years. Each presented with cardiac enlargement and varying degrees of left ventricular failure. One patient was known to have had complete heart block from infancy and another patient from 13 years of age. Each had chronic atrial fibrillation or flutter, with a regular ventricular rhythm at 35 to 45/min. Hemodynamic studies showed dilatation and poor contractility of the left ventricle, considerable mitral regurgitation, reduced resting cardiac output and elevated left ventricular end-diastolic pressures. The clinical course in follow-up periods of up to 5 years has been one of relatively mild, slowly progressive congestive heart failure. Mitral valve replacement and permanent pacemaker installation in one patient had no effect on the clinical course. The mitral valve showed redundant leaflet tissue with mucoid degenerative changes. This syndrome appears to represent a form of congenital cardiomyopathy which involves degeneration or fibrotic changes in both the myocardium and the conduction system. Familial occurrence has not been recognized.     

Serologic diagnosis of access device-related staphylococcal bacteremia.

Staphylococcal bacteremia occurs frequently in patients undergoing long-term hemodialysis (dialysis patients). Although such bacteremia is frequently uncomplicated, it may be associated with endocarditis, metastatic infection or suppuration at the access site requiring excision of the access device for control of the infection (complicated bacteremia). To distinguish patients with uncomplicated bacteremia from those with complications, we measured staphylococcal teichoic acid antibodies by agar-gel diffusion and immunoglobulin G (IgG) antibodies by radioimmunoassay in 18 patients with staphylococcal bacteremia undergoing long-term hemodialysis. Although teichoic acid antibodies were not detected in five patients with uncomplicated bacteremia, they were observed in only three of 13 patients with complicated bacteremia. IgG staphylococcal antibodies were present in 10 of 13 patients with complicated bacteremia compared to none of five patients with uncomplicated bacteremia compared to none of five patients with uncomplicated bacteremia (p less than 0.05). Thus, radioimmunoassay was spuerior to agar-gel diffusion in identifying dialysis patients with complicated bacteremia. In patients with increased concentrations of IgG staphylococcal antibodies by radioimmunoassay, the diagnosis of endocarditis, metastatic infection and suppuration at the access site should be considered. Prolonged antibiotic therapy and/or operative removal of the access device may be necessary.     

Legionella pneumophila pericarditis proved by culture of pericardial fluid

Serogroup 1 Legionella pneumophila was isolated from the pericardial fluid of a nonimmunosuppressed patient with pulmonary infiltrates, cardiac tamponade, and histologic evidence of pericarditis. This is the first reported case in which the association of L. pneumophila infection and pericarditis has been proved by growth of the organism from pericardial fluid. Physicians caring for patients with pericarditis of unknown cause should consider L. pneumophila in their differential diagnosis because special diagnostic efforts and relatively specific therapy are required for its optimal management.