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Biomedical subjects

R E McCabe

Publications and source records attributed to R E McCabe.

At least 37 records · Page 2Linked to original sources
PubMed1990

Current diagnosis and management of toxoplasmosis in cancer patients.

Toxoplasmosis should be considered as a potential pathogen in cancer patients who have clinical syndromes, especially lymphadenopathy, for which the cause is not clear. Patients with reticuloendothelial malignancies or solid cancers treated with systemic chemotherapy or with progressive disease appear to be at particular risk for life-threatening toxoplasmosis. There has also been an explosion in the number of cases of toxoplasmic encephalitis in patients infected with HIV. Diagnosis rests on demonstration of trophozoites in tissue or body fluids, demonstration of characteristic serologic test results, and, in cases of lymphadenopathy, characteristic histologic features.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Mycobacterium fortuitum infection in a patient with a penile prosthesis. Case report.

A 47-year-old male with a Mentor penile prosthesis presented with purulent drainage eight months after implantation. In addition to other organisms, routine cultures from the implant site yielded Mycobacterium fortuitum, an association never reported previously in the literature. Infection resolved with removal of the implant and antibiotic therapy.

Humans↗
PubMed1989

Trypanosoma cruzi: explant organ cultures from mice with chronic Chagas' disease.

Explants of 13 different organs obtained from C3H/HEN, Swiss-Webster, and C57Bl/6 mice chronically infected with Trypanosoma cruzi (Y strain) were cocultivated with mouse embryo fibroblasts to determine the organs that contain T. cruzi during the chronic infection. Explant cultures frequently yielded T. cruzi as late as 12 months after infection. Spleen and skeletal muscle were most frequently positive; heart cultures were rarely positive in any mouse strain. C3H/HEN mice had significantly more cultures positive than Swiss-Webster mice, as expected from relative susceptibility of C3H/HEN mice to acute infection. In contrast, C57Bl/6 mice, relatively resistant to acute infection, had significantly more cultures positive at 12 months of infection than Swiss-Webster mice. Also, C57Bl/6 mice had a significant increase in the number of positive cultures at 12 months of infection compared to 6 months of infection. These results show that organisms can be recovered routinely from some tissues during the chronic infection, that murine susceptibility to infection should differentiate between acute and chronic infection, and that C57Bl/6 mice may lose control of infection during the chronic infection.

Acute Disease↗
PubMed1989

Open lung biopsy in patients with Hodgkin's disease and pulmonary infiltrates.

Although open lung biopsy (OLB) is frequently employed for diagnosis of pulmonary lesions in patients with Hodgkin's disease, the actual efficacy of the procedure in establishing a diagnosis in these patients, and its effect on their treatment and clinical outcome, have not been evaluated. We reviewed the results of OLB in 41 patients with previously diagnosed Hodgkin's disease (17 with stage II disease, 10 with stage III, and 14 with stage IV) who had pulmonary opacification on chest roentgenogram. Nineteen (46%) diagnoses were specific and 22 nonspecific. The most common specific diagnosis was Hodgkin's disease (12 patients); the others were Pneumocystis carinii pneumonia (3), solitary fungal granuloma (2), cytomegalovirus pneumonia (1), and primary lung adenocarcinoma (1). Specific diagnoses were made in 11 (69%) of 16 patients with discrete nodules or masses but in only eight (32%) of the 25 patients with non-nodular radiographic opacification. Eleven (58%) of 19 patients who were asymptomatic or had had symptoms for longer than 4 wk had specific diagnoses, compared to one of six patients (17%) symptomatic for 1 wk or less. Survival of hospitalization correlated more with stage of Hodgkin's disease than with specific diagnosis. However, treatment was changed after biopsy in 22 (54%) of the patients. The results suggest that OLB can be helpful in the management of patients with Hodgkin's disease and pulmonary infiltrates, both in establishing a diagnosis and in assisting the patients' management. OLB appears to be more helpful in patients with Hodgkin's disease than in patients with acute nonlymphocytic leukemia or the acquired immunodeficiency syndrome and pulmonary infiltrates.

Adolescent↗
PubMed1989

Open lung biopsy in patients with non-Hodgkin's lymphoma and pulmonary infiltrates.

Patients with non-Hodgkin's lymphoma (NHL) are at increased risk for pulmonary infection with opportunistic pathogens associated with diminished cell mediated immunity. Open lung biopsy (OLB) frequently is recommended for diagnosis of pulmonary infiltrates in patients with NHL, but its usefulness for patient management and outcome has not been evaluated for patients with NHL. We reviewed the results of 20 consecutive OLB in 19 patients with previously diagnosed non-Hodgkin's lymphoma at Stanford University Medical Center during a nine-year period. Fifteen patients had known active lymphoma at time of OLB, and no patient had granulocytopenia. Ten of the 20 OLBs yielded specific diagnoses. A greater proportion of patients with stage I or II disease had specific diagnoses than patients with more advanced NHL. Five of 14 patients considered to have had a life threatening illness at the time of OLB had specific diagnoses from OLB vs five of six patients considered clinically stable. Chest roentgenograms that had discrete masses or nodules correlated with ability to establish a specific diagnosis by OLB. For patients in whom the results of OLB were nonspecific, management appeared unaffected by the OLB. The OLB in NHL appeared most useful for detecting recurrent NHL in clinically stable patients with discrete nodules or masses on chest roentgenogram. Pneumocystis pneumonia was the only infection identified by OLB.

Biopsy↗
PubMed1989

Current recommendations and future prospects in the treatment of toxoplasmosis.

Toxoplasma infection is highly prevalent throughout the world and causes disease in diverse populations. Effective treatment regimens are available for each clinical entity of toxoplasma, but problems of incomplete clinical efficacy, drug potency, drug safety, and length of treatment remain. No well-controlled clinical trials in humans have been performed to evaluate the efficacy and safety of treatment. Primary treatment of toxoplasmosis is with the synergistic combination of pyrimethamine and sulphonamide. This is considered the treatment of choice for severe disease, disease in immunocompromised patients, and congenital toxoplasmosis. Spiramycin, a macrolide antibiotic, is frequently used alone or alternately with pyrimethamine and sulphonamide for pregnant women with the acute acquired infection to prevent congenital toxoplasmosis. Clindamycin is used frequently to treat acute flares of toxoplasmic chorioretinitis and as second-line therapy for toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome (AIDS). Inadequacies in the treatment of toxoplasmosis in immunosuppressed patients, exemplified by experience with AIDS patients, should provide the impetus for well-designed trials to find and evaluate more potent and better-tolerated agents. Classes of new drugs that have been investigated and show some promise include: (a) macrolides (roxithromycin, azithromycin); (b) folic acid antagonists (piritrexim and trimetrexate), and (c) purine analogues (arprinocid). Immunomodulators have attracted interest, and interferon-gamma alone and in combination with roxithromycin is effective in murine models. Interleukin-2 is also effective in the murine model.

Animals↗
PubMed1988

Hospital survey of antimicrobial prophylaxis to prevent endocarditis in patients with prosthetic heart valves.

The American Heart Association (AHA) has published guidelines for use of prophylactic antibiotics to prevent bacterial endocarditis, but few data are available about physician compliance with these guidelines. A retrospective review was conducted of the use of prophylactic antibiotics in patients with prosthetic heart valves who were undergoing diagnostic or operative procedures or heart catheterization at three hospitals. Compliance with AHA recommendations was only 30 percent (14 of 46) for procedures considered high risk for patients with prosthetic heart valves. Six (23 percent) of 26 patients who underwent right or left heart catheterization received prophylactic antibiotics (not recommended by AHA). Antibiotics were given to 42 (74 percent) of 57 patients who underwent surgical procedures considered at low risk of bacteremia, but only 33 (58 percent) received antibiotics that cover organisms commonly present at the site of the procedure. The results indicate that clinicians frequently do not administer prophylactic antibiotics in patients with prosthetic heart valves who are undergoing invasive procedures or do not follow published AHA guidelines when antibiotics are administered.

Adult↗
PubMed1988

Diagnosis of pulmonary infections in immunocompromised patients.

In an immunocompromised patient with fever and pulmonary infiltrates, it frequently is difficult to decide which invasive procedure, if any, to use to obtain a definitive diagnosis. Because most lung infiltrates in immunosuppressed patients are caused by bacteria and sputum usually is readily available for examination, empiric therapy with potent, safe, broad spectrum, antibacterial drugs often is successful. Invasive procedures that prove a diagnosis may result in substantive changes in therapy in perhaps as few as 10 to 20 per cent of patients, and the procedure itself may harm the patient. In a unique study in which patients with acute pneumonitis without neutropenia were randomized to either empiric antibiotic treatment or treatment based on results of open lung biopsy, patients with open lung biopsy had a worse outcome, possibly related to morbidity of open lung biopsy. Furthermore, no diagnoses were provided by open lung biopsy that were not treated by the empiric regimen. A missed treatable disease may be tragic, however. A thoughtful clinician must evaluate each patient with careful consideration of the history in light of the underlying disease and its treatment, rapidity of clinical course, physical examination, and laboratory data, particularly the chest radiograph, sputum examination, and bleeding parameters. Fiberoptic bronchoscopy with washings and brushings is very safe; the addition of transbronchial biopsy adds diagnostic power at the price of some complications. Bronchoalveolar lavage is a very promising technique that probably will find widespread use. However, none of the foregoing techniques is completely sensitive. When no diagnosis is established and bronchoscopy studies are negative, open lung biopsy must be considered, especially when the chest radiograph or computed tomography scan suggests focal disease or lymphadenopathy. Needle aspiration can be used, particularly if local experience is favorable and lung disease is peripheral. When evaluating a procedure, local experience must be considered rather than reliance on published diagnostic yields and complication rates. New diagnostic and therapeutic developments may change decision analysis in the near future. At present, cultures for viruses and fungi and serologic techniques have little application at most medical centers, and decisions on data from invasive procedures pivot on interpretation of histology and smears. Development of assays for antigen (for example, Aspergillus) and rapid culture techniques (for example, cytomegalovirus and the shell vial method), coupled with new, effective antimicrobials, may demand maximum effort for a definitive diagnosis in every patient.

Bacterial Infections↗
PubMed1988

Primaquine is lethal for intracellular but not extracellular Trypanosoma cruzi.

Primaquine has been used to treat Chagas' disease in humans and has been reported to be active against extracellular Trypanosoma cruzi. Experiments were designed to evaluate the relative activity of primaquine against extra- and intracellular T. cruzi and to determine if primaquine might be combined advantageously with ketoconazole. Primaquine at 0.5 micrograms/ml significantly inhibited T. cruzi replication in infected mouse peritoneal macrophages and also effectively treated infected L929 cells. To examine the effect of primaquine on extracellular organisms, tissue culture T. cruzi were incubated with primaquine for different periods of time and then used to infect macrophages. Incubation with 10 micrograms/ml for 14 hr but not 8 hr significantly inhibited but did not eradicate replication. Incubation of spleen amastigotes or blood trypomastigotes for 2 hr with 10 micrograms/ml did not inhibit replication. Incubation of extracellular tissue culture T. cruzi with primaquine for 2 hr did not potentiate the activity of ketoconazole against intracellular organisms. The combination of primaquine and ketoconazole administered to acutely infected mice significantly decreased parasitemias in comparison to treatment with primaquine or ketoconazole alone. Thus primaquine acts primarily on intracellular rather than extracellular T. cruzi. Primaquine and ketoconazole appear to have additive activity in vivo.

Animals↗
PubMed1988

Perinephric abscess. Modern diagnosis and treatment in 47 cases.

The records of 47 patients with a perinephric abscess diagnosed from 1975 to 1986 at 8 San Francisco Bay Area hospitals were reviewed. The mean age was 51 years. Fifty-five percent were females and 45%, males. The left kidney was affected in 47% of cases, the right kidney in 40%, both in 4%, and a transplanted pelvic kidney in 9%. Fever (55%), chills or diaphoresis (47%), flank pain (40%), abdominal pain (40%), and nausea or vomiting (32%) were the most common presenting symptoms. About half the patients had symptoms for 1 week or less and 12% had no symptoms. Fever was documented before diagnosis in 88% of patients. Abdominal mass (13%) or tenderness (49%), and flank mass (9%) or tenderness (42%) were seen less frequently, and 11% of patients did not have fever, flank, or abdominal findings. The most frequent underlying conditions included previous urologic surgery (45%), previous urinary tract infection (38%), diabetes mellitus (36%), and urinary tract stones (36%). Cultures of perinephric abscesses yielded gram-negative aerobes in 52% of patients, primarily Escherichia coli. Staphylococcus aureus was isolated in 26% of patients and anaerobes in 17%. A single pathogen was isolated in 71% and multiple isolates in 29%. Of interest and great potential therapeutic importance was culture of anaerobes, primarily Bacteroides spp. in 17%, Enterococcus spp. in 7%, and Candida albicans in 7%. Positive blood and urine cultures identified perinephric abscess organisms exactly in 58% and 37% of cases, respectively. Routine laboratory tests such as the white blood cell count and urinalysis were insensitive and non-specific for perinephric abscess. Leukocytosis and anemia at admission were seen in slightly more than half of the patients. For radiologic diagnosis, computerized tomographic scanning was most helpful. Ultrasound and intravenous pyelography were falsely negative in about one-third of cases. Mortality (13%) was low in this series when compared with earlier studies, and probably reflects modern medical care. Six patients (13%) died during hospitalization, 2 of whom had diagnosis of PNA established only at autopsy. Drainage of the perinephric abscess was carried out by open surgical drainage in 64% of patients, percutaneous drainage in 19%, and both in 13%. The initial procedure, whether open surgical drainage or percutaneous catheter drainage, was usually successful. Late complications included nephrocutaneous fistulas in 3 patients and disseminated candidiasis in 1 patient.

Abscess↗
PubMed1987

Oral norfloxacin versus parenteral treatment of nosocomial urinary tract infection.

In a multiclinic, randomized trial, oral norfloxacin, a fluoroquinolone antibacterial, was compared with several standard parenteral regimens for the treatment of nonbacteremic, hospital-acquired urinary tract infections. Parenteral antibiotic agents included aminoglycosides alone; aminoglycosides in combination with either broad-spectrum penicillins or first-generation cephalosporins; or cefotaxime alone. Ninety-two percent of bacterial isolates were multiresistant gram-negative rods including Pseudomonas aeruginosa (31 percent), Escherichia coli (17 percent), Klebsiella/Enterobacter species (14 percent), and Serratia species (11 percent). In the first evaluable 94 patients, norfloxacin was comparable to the parenteral agents in eliminating infecting bacteria from the urine. Similarly, combined bacterial eradication and clinical cure or improvement occurred in 96 percent (76 percent with cures, 20 percent with improvement) of those treated with norfloxacin and 88 percent (67 percent with cures, 21 percent with improvement) of those treated with parenteral agents. A negative outcome (i.e., failure, superinfection, or reinfection) occurred in two (4 percent) norfloxacin-treated patients versus six (12 percent) parenterally treated patients. Adverse effects were few, infrequently drug related, and rarely serious (one with norfloxacin versus two with parenteral agents). Additionally, drug, preparation, and administration costs were substantially less with oral norfloxacin compared with the parenteral agents. The data suggest, therefore, that oral norfloxacin can be substituted for commonly used parenteral antibiotic regimens, without any compromise in efficacy, in the treatment of nonbacteremic patients with multiresistant, nosocomial urinary tract infections.

Adult↗
PubMed1987

Ketoconazole promotes parasitological cure of mice infected with Trypanosoma cruzi.

Administration of 120 mg/kg/day of ketoconazole for 9 weeks resulted in parasitological cure of at least 78.5% of mice infected with 10(5) blood trypanosomes of Trypanosoma cruzi, strain Y. These results and the fact that ketoconazole is widely used in humans for prolonged therapy of fungal infections without significant side effects strongly suggest that further evaluation of ketoconazole for treatment of Chagas disease is highly desirable.

Animals↗
PubMed1987

Unique differences in infectivity and seroreactivity of Toxoplasma harvested from mice infected for different lengths of time.

For use in experiments, Toxoplasma of the RH strain are usually harvested from mouse peritoneal cavities 48 hr (2-day Toxoplasma) or more after intraperitoneal inoculation. In this report we show that Toxoplasma harvested at 24 hr (1-day Toxoplasma) after inoculation are much more infective for and replicate to a greater degree within mouse resident peritoneal macrophages in vitro and are much more resistant to the cidal activity of activated mouse peritoneal macrophages and resident rat peritoneal macrophages than are 2-day Toxoplasma. Ingestion of 1-day Toxoplasma by macrophages did not trigger the respiratory burst as measured by reduction of nitroblue tetrazolium (NBT), but coating 1-day Toxoplasma with specific antibody did result in reduced NBT. However, coating 1-day Toxoplasma with specific antibody did not markedly decrease infectivity for macrophages in vitro, unlike decreased infectivity observed when 2-day Toxoplasma are coated with specific antibody. Use of 1-day Toxoplasma in the dye test resulted in a 5-fold decrease in titer of specific antibody in human sera. Use of Toxoplasma harvested 24 hr after infection may serve as a new tool to probe virulence factors of Toxoplasma and of host cells' antimicrobial mechanisms.

Animals↗
PubMed1986

The effects of cyclosporine on Toxoplasma gondii in vivo and in vitro.

We examined the effect of cyclosporine on Toxoplasma infection in vivo and in vitro. Administration to mice of 150 mg/kg/day cyclosporine variably affected mortality in four separate experiments. IgG (Sabin-Feldman dye test) and IgM enzyme-linked immunosorbent assay antibody titers were significantly depressed in mice treated with cyclosporine. These results suggested the possibility that cyclosporine possesses anti-Toxoplasma activity. Thus, macrophages were incubated with cyclosporine before and after infection with Toxoplasma. Treatment with 0.5, 1, and 5 micrograms cyclosporine/ml during or after challenge of macrophage monolayers with Toxoplasma inhibited replication of Toxoplasma (and resulted in killing of Toxoplasma). The effect of cyclosporine on development of activated macrophages was studied. Cyclosporine administered to mice at a dose of 150 mg/kg/day neither accelerated nor delayed activation of macrophages (assessed by inhibition of Toxoplasma replication in vitro) by i.v. injection of either Corynebacterium parvum or Toxoplasma. Cyclosporine affects mortality variably in murine toxoplasmosis, depresses synthesis of IgG and IgM Toxoplasma antibody in vivo, does not prevent activation of macrophages in vivo, and possesses anti-Toxoplasma activity in vitro and perhaps in vivo. Cyclosporine may be the preferred immunosuppressive agent for recipients of an organ transplant who are at high risk for toxoplasmosis (e.g., seronegative recipients who have received organ from seropositive donors).

Animals↗
PubMed1986

Mechanisms of killing of Toxoplasma gondii by rat peritoneal macrophages.

Rats are resistant to Toxoplasma infection, and macrophages are thought to mediate this resistance. We performed a series of experiments to investigate the mechanism of the anti-Toxoplasma activity of resident rat peritoneal macrophages. Resident rat peritoneal macrophages killed more than 90% of ingested Toxoplasma gondii in vitro. This capacity was reduced progressively with the prolongation of culturing of macrophages in vitro before challenge with T. gondii. Exhaustion of the respiratory burst of macrophages with phorbol myristate acetate impaired their ability to kill and limit the replication of T. gondii. Histidine and diazabicyclooctane, presumed scavengers of singlet oxygen, were the only members of a battery of scavengers of metabolites of the respiratory burst that impaired the anti-Toxoplasma activity of macrophages. Ingestion of heat-killed Candida albicans by macrophages reduced large amounts of intracellular Nitro Blue Tetrazolium dye, whereas little dye was reduced by the ingestion of T. gondii. Challenge of macrophages with T. gondii released no detectable superoxide anion, as measured by the reduction of ferricytochrome c, whereas stimulation of macrophages with phorbol myristate acetate or ingestion of heat-killed Candida by macrophages released abundant superoxide anion. These data are consistent with the contributions of oxygen-dependent and oxygen-independent mechanisms to the anti-Toxoplasma activity of rat peritoneal macrophages. In addition, neonatal rats are known to be susceptible to Toxoplasma infection in vivo. However, resident neonatal rat peritoneal macrophages ingested and killed T. gondii to the same extent as did adult macrophages. Thus, the susceptibility of neonatal rats to Toxoplasma infection probably resides in other aspects of macrophage function or the immune response.

Animals↗
PubMed1986

In vitro and in vivo effects of itraconazole against Trypanosoma cruzi.

The synthetic imidazole, itraconazole, was examined for in vitro and in vivo activity against Trypanosoma cruzi. Mice treated with concentrations as low as 15 mg itraconazole/kg/day were completely protected against death due to infection with any of three different and highly virulent strains of T. cruzi. Treatment of infected mice with 120 mg itraconazole/kg/day for seven to nine weeks apparently resulted in the parasitologic cure as determined by negative hemocultures and subinoculations, negative serology for T. cruzi, and absence of parasites in histologic sections following completion of therapy. Peak serum levels of itraconazole after treatment of mice with the dose of the drug that provided protection against death were less than 1 microgram/ml. Experiments in vitro revealed that concentrations of itraconazole as little as 0.001 microgram/ml inhibited replication of intracellular amastigotes in macrophages. These results indicate that itraconazole has a remarkable activity against T. cruzi. Further investigation of intraconazole as a therapeutic agent for Chagas' disease may be warranted.

Animals↗