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Biomedical subjects

R E McCabe

Publications and source records attributed to R E McCabe.

At least 55 records · Page 3Linked to original sources
PubMed1985

Open lung biopsy in patients with acute leukemia.

The results of open lung biopsy in 15 patients with acute leukemia, pulmonary infiltrates, neutropenia, and fever were reviewed. The patients averaged 26 hospital days of neutropenia and 20 hospital days of fever before open lung biopsy, and all patients received broad-spectrum antibacterial agents (mean 17 days) before open lung biopsy. Nine (67 percent) received amphotericin B prior to open lung biopsy (mean 22 days). Open lung biopsy yielded a specific clinically helpful diagnosis in six patients, but only two of these patients survived the hospitalization during which open lung biopsy was performed. Open lung biopsy detected fungus in four patients and leukemic infiltrates in two patients. Management was appropriately modified in these patients. In nine patients, a specific diagnosis of the pulmonary infiltrate was not obtained by open lung biopsy. Antimicrobial regimens were not changed substantially for these patients. In six patients, the results of open lung biopsy may have been misleading. Two patients had pulmonary fungal diseases at autopsy, undetected by open lung biopsy eight days and five weeks prior to death. Another patient had invasive aspergillosis and one had cytomegalovirus pneumonitis not detected by open lung biopsy. Two patients had false-positive preliminary histologic reports of pulmonary infection. On the basis of this experience, in this specific population of patients, open lung biopsy was often of little help in directing medical therapy or influencing clinical outcome.

Adolescent↗
PubMed1985

In vitro and in vivo activities of formycin B against Trypanosoma cruzi.

The inosine analog formycin B was examined for in vitro and in vivo activities against Trypanosoma cruzi. concentration of formycin B as low as 0.1 microgram/ml markedly inhibited intracellular multiplication of T. cruzi strains both in macrophages and in L929 cells. Mice infected with 10(5) blood form trypomastigotes of the highly virulent strain Y of T. cruzi were completely protected against death by treatment with 11.8 or 5.9 mg of formycin B per kg administered intraperitoneally each day for 19 days. Four different strains of T. cruzi were used, and each was susceptible to formycin B administered either intraperitoneally or orally. Parasitological cure, however, was not achieved with any of the treatments used, including prolonged treatment for up to 10 weeks. Formycin B has a remarkable capacity for inhibiting the in vitro intracellular replication of T. cruzi and protecting mice against death due to the acute infection with the organism. It does not appear, however, to be able to completely eliminate T. cruzi from infected mice.

Animals↗
PubMed1985

In vivo and in vitro effects of cyclosporin A on Trypanosoma cruzi.

The in vivo and in vitro effects of cyclosporin A on T. cruzi were examined. Mice receiving 150 or 75 mg/kg/day of cyclosporin A and infected with T. cruzi 48 hr later had significantly higher parasitemias and earlier mortality than controls. Mice receiving cyclosporin A after infection had parasitemias similar to controls. Infections with both the reticulotropic Y and the miotropic CL strains of T. cruzi were enhanced by cyclosporin A. The in vitro replication of epimastigotes, but not the intracellular replication of amastigotes, in mouse macrophages was inhibited by 5 micrograms cyclosporin A/ml. Enhancement of the infection by cyclosporin A was not due to an effect on macrophages since the drug did not prevent development of activated macrophages capable of killing intracellular T. cruzi.

Animals↗
PubMed1984

Toxoplasmic encephalitis in patients with acquired immune deficiency syndrome.

An epidemic of cases of toxoplasmic encephalitis is occurring in patients with acquired immune deficiency syndrome (AIDS). Serological or histopathologic studies were performed on 70 cases with AIDS and toxoplasmic encephalitis. In many cases conventional stains of brain-tissue specimens failed to disclose Toxoplasma organisms; all were positive when stained by the peroxidase-antiperoxidase technique. Except for a single patient, serological titers were not indicative of an acute acquired infection. The ratio of titers in the agglutination test to titers in the Sabin-Feldman dye test seemed to be more predictive of active toxoplasmic encephalitis in patients with AIDS than either test alone. Based on histological and serological data, an approach is presented for diagnosis and treatment of suspected toxoplasmic encephalitis in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Ketoconazole inhibition of intracellular multiplication of Trypanosoma cruzi and protection of mice against lethal infection with the organism.

The effects of ketoconazole against infection with Trypanosoma cruzi both in vivo and in vitro were examined. In vivo, ketoconazole significantly protected mice infected with lethal inocula of the Y strain of T. cruzi even when treatment was initiated seven days after infection; protection was also demonstrated for three other strains. Although mice had demonstrable parasitemia after completion of therapy, tissue sections of treated mice revealed a complete absence of organisms. Concentrations of ketoconazole as low as 0.001 microgram/ml inhibited in vitro replication of intracellular organisms, whereas concentrations of ketoconazole that prevented replication of intracellular amastigotes had no effect on extracellular organisms. This finding and the observation that inhibition of replication of amastigotes occurred in macrophages exposed to ketoconazole before infection suggests that the inhibitory effect depends on interaction of the drug with host cells. Thus ketoconazole should be tested as a therapeutic agent for Chagas' disease in humans.

Animals↗
PubMed1984

Mechanisms of invasion and replication of the intracellular stage in Trypanosoma cruzi.

Amastigotes obtained from spleens of mice infected with different strains of Trypanosoma cruzi were examined for their ability to invade macrophages and L929 cells and to initiate infection in mice. Both types of cells were readily invaded by organisms of the strains Y, MR, and Tulahuen. Organisms of the CL strain were taken up by both types of cells at a rate that was significantly lower than that for organisms of the other strains. However, all strains multiplied intracellularly. Activated macrophages inhibited the replication of intracellular organisms. Treatment of normal macrophages with cytochalasin B, trypsin, chymotrypsin, or pronase significantly inhibited phagocytosis, but the inhibitory effect was reversible. Mice injected with spleen amastigotes developed parasitemia and died of the infection. These results demonstrate that spleen amastigotes are able to infect, survive, and replicate within professional and nonprofessional phagocytes and to initiate infection in vivo. Interiorization of spleen amastigotes is by phagocytosis and is dependent upon a protease-sensitive receptor(s) on the cell surfaces of host macrophages.

Animals↗
PubMed1984

C-reactive protein in patients with bacteremia.

Quantitative measurement of C-reactive protein (CRP) in serum has been proposed as a sensitive and, for some populations, a specific indicator of infection. To determine whether early measurement of CRP in serum could differentiate patients with bacteremia from a control group of patients whose blood cultures yielded contaminants, we measured CRP concentrations quantitatively by rate nephelometry in serum samples that had been obtained from patients on the same day as blood samples that yielded bacteria or fungi. Of the 36 episodes of bacteremia, 3 (8.5%) occurred in patients with normal concentrations of CRP in serum and 2 (5.5%) in patients with minimally elevated levels. Of the 21 episodes associated with contaminated blood cultures, only 2 (9.5%) occurred in patients with normal CRP levels. Of the patients with marked elevations of CRP (greater than 10 mg/dl), 18 (86%) had infection, although not all of these patients had bacteremia. We conclude that a normal concentration of CRP in serum does not eliminate the possibility of bacteremia. Moderate elevations (1 to 10 mg/dl) of CRP levels are common in both patients with contaminated blood cultures and in those with bacteremia. If the CRP concentration in serum is greater than 10 mg/dl and if other causes of marked elevations of CRP levels are eliminated, CRP concentration in serum may be a relatively specific indicator of infection. However, elevations of CRP concentrations are neither completely sensitive nor specific for detecting infection in patients with bacteremia.

Adolescent↗
PubMed1984

Prosthetic valve endocarditis caused by Legionella pneumophila.

Prosthetic valve endocarditis due to Legionella pneumophila occurred in a woman who had aortic and mitral valve replacements with porcine xenografts. During surgery for persistent fever and aortic regurgitation due to presumed endocarditis, she had vegetations involving both the aortic and mitral valve prostheses with a circumferential abscess of the aortic annulus. Cultures, Dieterle stain, and direct fluorescent antibody stain of valve tissue, and subsequent measurements of serum antibody levels confirmed L. pneumophila as the infecting organism. This infection occurred in the absence of pneumonia. Legionella pneumophila must be considered a potential cause of culture-negative prosthetic valve endocarditis and should be sought in appropriate clinical circumstances.

Aortic Valve↗
PubMed1984

The use of hemoglobin solutions in kidney perfusions.

Solutions of hemoglobin have often been considered for both hypothermic and normothermic perfusion of isolated kidneys. This paper considers basic issues, preparative techniques, and the viscosity of hemoglobin solutions, as well as the demands made by the kidney on a perfusate. The natural system of oxygen transport in higher animals is complex, and its perturbation to produce convenient hemoglobin-based renal perfusates produces numerous problems. The desirable effect of 2,3-diphosphoglycerate is not easily maintained in a perfusate, but its inclusion can be avoided by appropriate choice of species donating hemoglobin. Hemoglobin tetramer in free solution may dissociate and be lost by glomerular filtration. Ferric hemoglobin, the dominant form at redox equilibrium, is useless for oxygen transport; the ferrous form is maintained in the erythrocyte by reducing metabolites and, under normothermic conditions, the ferrous to ferric conversion is slow but significant. Methods for lysis of erythrocytes and removal of their stroma are discussed; reduction of ferric hemoglobin by chemical agents and electrolysis are considered in detail; and means for adjusting concentration and solute background are presented. The need for carbonic anhydrase in hemoglobin solutions used as perfusates is shown and methods for its provision are discussed. A review of viscometric data for hemoglobin solutions is provided to which original data are added. Hemoglobin solutions show a temperature-independent intrinsic viscosity, according to Einstein's theory for a molecule of 23 A radius. The O2 and CO2 transport requirements of renal perfusates are analyzed comprehensively. The normothermic kidney has an unusual respiration pattern, requiring an amount of oxygen that is not fixed but, rather, proportional to the total blood flow rate. In canines the average arterio-venous O2 content difference found by many investigators is 2.14 vol%; the corresponding CO2 value is 2.47 vol%; and the respiratory quotient is greater than unity. Wide limits of PO2, but not P CO2 in perfusate, appear allowable. A final section evaluates hemoglobin solutions as both normothermic and hypothermic renal perfusates from the viewpoints of blood gas chemistry, urinary loss, oncotic pressure, fatty acid carrying capacity, viscosity, and the need for functions usually attributed to platelets. It is concluded, overall, that perfusates containing free hemoglobin have only a limited role to play in renal perfusion.

Animals↗
PubMed1983

Ketoconazole protects against infection with Trypanosoma cruzi in a murine model.

The oral administration of ketoconazole to mice protected them against death caused by infection with Trypanosoma cruzi. The addition of ketoconazole to cultures of macrophages infected with the organism markedly inhibited the intracellular multiplication of amastigotes. These observations suggest that ketoconazole may be a potent agent against T. cruzi and should be evaluated more extensively as a chemotherapeutic agent for Chagas' disease.

Animals↗
PubMed1980

International transoceanic kidney sharing.

The shortage of cadaver kidneys for transplantation persists in most regions of the United States. Because so many patients have preformed antibodies against prospective donors, identification of appropriate donor-recipient pairs is proving difficult in spite of computerized interregional sharing. To avoid wasting valuable human organs, we have shared 11 kidneys between Italy, the Soviet Union, West Germany and the USA, 10 of which resulted in successful transplants. Such sharing guarantees better utilization of kidneys bilaterally and aids in transplanting cytotoxic patients by increasing the total number of kidneys available.

Cadaver↗
PubMed1980

The protective effect of methyl prednisolone on the machine-preserved kidney.

Fifty cadaveric transplants were reviewed to determine whether graft failure was related to the method of preservation. Twenty-eight transplants were preserved by a combination of cold storage and perfusion with cryoprecipitated plasma. Twenty-two transplants were preserved by continuous perfusion with Plasmanate. The perfusate of 14 plasma-perfused kidneys contained 1.0 g of methyl prednisolone, whereas the Plasmanate contained only 100 mg hydrocortisone. Fourteen plasma-perfused kidneys functioned immediately (Group I), and 14 showed delayed function. Seventeen of 22 Plasmanate kidneys (Group III) functioned immediately. Of the Group I kidneys, 13 of 14 functioned for three to eight months, and eight (57%) are still functioning after two years vs. only three of 14 (21%) in Group II. Eleven of the 14 long-term surviving grafts were pretreated with methyl prednisolone. Only nine of the Plasmanate kidneys (39%) lasted more than three months; five (22%) survived more than 12 months. None of the Plasmanate-perfused kidneys that failed to function immediately lasted three months. It is concluded that immediate restoration of renal function after transplantation is a favorable sign for long-term graft survival. The addition of methyl prednisolone to the perfusate may enhance the survival of kidney allografts.

Graft Survival↗