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R Saral

Publications and source records attributed to R Saral.

At least 127 records · Page 7Linked to original sources
PubMed1982

Differences in virulence of clinical isolates of Candida tropicalis and Candida albicans in mice.

Prior reports from this institution indicated that Candida tropicalis was more pathogenic than C. albicans in oncology patients. Pairs of clinical isolates of C. tropicalis and C. albicans recovered from similar patients at other institutions were examined to determine their relative virulence. After intravenous inoculation in normal mice, three pairs of isolates had no significant differences in the 50% lethal dose, and one C. tropicalis isolate was less virulent than its companion C. albicans isolate. In contrast, in mice treated with antibiotics and cytarabine, an antineoplastic drug which damages the gastrointestinal mucosa and produces granulocytopenia, oral inoculation of yeast cells produced striking differences in the 50% infective dose: each C. tropicalis isolate was more virulent than the companion C. albicans isolate from the same institution. The increased virulence of the C. tropicalis isolates compared with the C. albicans isolates when given orally to compromised mice parallels clinical observations in compromised patients.

Agranulocytosis↗
PubMed1982

Bone marrow transplantation with major ABO blood group incompatibility using erythrocyte depletion of marrow prior to infusion.

Twenty-five patients with major ABO blood group incompatibility between donor and recipient underwent allogeneic bone marrow transplantation using erythrocyte depletion of the bone marrow infusate prior to administration. Over 95% of the original erythrocyte content of the marrows was removed, while retaining 75% of the mononuclear cell content and 57% of the granulocyte-monocyte colony-forming units. Recipients, well hydrated and premedicated with corticosteroids, diphenhydramine, and mannitol, tolerated infusions well. The frequency of engraftment, rate of recovery of peripheral blood leukocytes, granulocytes, and platelets, and the incidence of graft-versus-host disease was similar to that observed following ABO blood group compatible bone marrow transplantation. Erythroid development following ABO blood group incompatible transplantation was significantly impaired until hemagglutinins fell to 1:4 or lower, at which time recovery of erythrocytes was detected in the peripheral blood. The erythrocyte hypoplasia associated with incompatible hemagglutinins was temporary. Erythrocyte purging is a safe and effective technique to perform bone marrow transplantation across major ABO blood group incompatibilities.

ABO Blood-Group System↗
PubMed1981

Acyclovir prophylaxis of herpes-simplex-virus infections.

We conducted a double-blind, placebo-controlled study of acyclovir prophylaxis against infection with herpes simplex virus (HSV) in 20 seropositive recipients of bone-marrow transplants. Acyclovir or placebo was administered for 18 days, starting three days before transplantation. Culture-positive HSV lesions developed during the study in seven of the 10 patients who received placebo. In contrast, no such lesions appeared in the 10 patients who received acyclovir (P congruent to 0.003). None of the patients had evidence of drug toxicity. Five of the patients treated with acyclovir had mild culture-positive HSV infections after cessation of the drug, and two additional patients shed virus without having lesions. Acyclovir appears to be a potent inhibitor of HSV replication. Although acyclovir does no appear to eradicate latent infection, it can provide effective prophylaxis against reactivated infections.

Acyclovir↗
PubMed1981

Efficacy of acyclovir against mouse cytomegalovirus in vivo.

Acyclovir reduced mortality and organ virus titers in mice inoculated intraperitoneally with 10 50% lethal doses of mouse cytomegalovirus. This susceptibility to acyclovir of a herpesvirus which lacks thymidine kinase is surprising. Alternative phosphorylating enzymes may account for this susceptibility.

Acyclovir↗
PubMed1981

Activity of trifluorothymidine against cytomegalovirus.

Trifluorothymidine (TFT) was tested for antiviral activity against mouse cytomegalovirus (MCMV) and human cytomegalovirus (HCMV) in one-step replication assays. The TFT concentration required to reduce virus yield by 50% (ID50) was 0.22 microM for MCMV and 0.012 microM for HCMV. The antiviral activity of TFT against MCMV was reversed by addition of equimolar thymidine, and no antiviral activity was demonstrable in a host cell line lacking thymidine kinase. Thus, TFT's anti-MCMV activity is dependent on a host cell TK since this herpesvirus lacks thymidine kinase. A continuous subcutaneous infusion of TFT achieving a serum concentration of 1 microM failed to protect mice from lethal MCMV infection, perhaps because serum levels of thymidine were comparable to the drug level. Comparison of the ID50 against HCMV and the ID50 against human bone marrow progenitor cells resulted in an in vitro therapeutic ratio of 108, suggesting that TFT might offer some promise as a clinically useful anti-HCMV agent.

Animals↗
PubMed1981

Thymidine kinase not required for antiviral activity of acyclovir against mouse cytomegalovirus.

Previous studies of herpesvirus infections have indicated that a virus-specified thymidine kinase is required for the initial phosphorylation of acyclovir [acycloguanosine or 9-(2-hydroxyethoxymethyl)guanine] in the formation of acycloguanosine triphosphate. The latter compound accumulates in infected cells and competitively inhibits the viral DNA polymerase. We found that mouse cytomegalovirus, which does not express a thymidine kinase, was sensitive to the antiviral effects of acyclovir at a 50% inhibitory dose of approximately 0.23 microM. Acyclovir was equally effective against mouse cytomegalovirus in normal 3T3 cells and in 3T3 cells deficient in cellular thymidine kinase. Furthermore, the activity of acyclovir could not be reversed by excess thymidine, which easily reversed the antiviral activity of acyclovir against herpes simplex virus. Using a high-pressure liquid chromatography technique that easily detected acycloguanosine triphosphate in cells infected with herpes simplex virus, we could not detect acycloguanosine triphosphate in mouse cytomegalovirus-infected cells. These experiments demonstrated that the activity of acyclovir against mouse cytomegalovirus is not dependent on a thymidine phosphorylation pathway. Additional experiments are underway to determine whether acycloguanosine triphosphate is produced by another pathway in concentrations sufficient to inhibit mouse cytomegalovirus DNA polymerase.

Acyclovir↗
PubMed1981

Toxoplasmosis: a treatable neurologic disease in the immunologically compromised patient.

A 10-year-old girl with aplastic anemia developed seizures and a mild hemiparesis following a bone marrow transplant. Based on serologic evidence and a computed tomography scan, which showed a left parietal lucency with ring enhancement, a diagnosis of toxoplasmosis was considered. A brain biopsy of the lucent area demonstrated the inflammation and necrosis but no organisms were seen. During a six-week course of pyrimethamine, sulfadiazine, and folinic acid therapy there was clinical and neuroradiologic resolution. The short course of therapy as well as the inadvertent substitution of folic acid for folinic acid and trimethoprim-sulfamethoxazole for sulfadiazine resulted in the reappearance of neurologic deficits. Reinstitution of appropriate therapy produced gradual improvement over a nine-month period. Serial computer tomography scans correlated with the clinical course. In the immunologically compromised host CNS toxoplasmosis should be considered in the differential diagnosis of an evolving CNS syndrome. Early detection and prolonged therapy with appropriate drugs can result in a favorable outcome. Computed tomography scanning may be helpful in diagnosis and follow-up.

Anemia, Aplastic↗
PubMed1980

Carbenicillin-trimethoprim/sulfamethoxazole versus carbenicillin-gentamicin as empiric therapy of infection in granulocytopenic patients. A prospective, randomized, double-blind study.

The results of therapy with carbenicillin plus trimethoprim-sulfamethoxazole (C-T/S) were compared to those obtained with carbenicillin plus gentamicin (C-G) in a prospective double-blind study of empiric antibiotic therapy in granulocytopenic patients. Patients were stratified into two groups: favorable-prognosis, group 1 (carcinoma, lymphoma, multiple myeloma), or unfavorable-prognosis, group 2 (acute leukemia, bone marrow transplantation), based on anticipated duration of granulocytopenia. Over-all, empiric antibiotic trials were more often successful (P = 0.004) in group 1 (55 of 62 patients or 89 per cent) than in group 2 (42 of 64 patients, 66 per cent)mwithin group 1, there was a favorable outcome in 30 of 32 (94 per cent) C-T/S trials and in 25 of 30 (83 per cent) C-G trials (P = 0.25); within group 2, there was a favorable outcome in 23 of 30 (77 per cent) C-T/S trials and in 19 of 34 (56 per cent) C-G trials (P = 0.14), Combined results in both groups indicated a higher proportion of favorable outcome in C-T/S trials (53 of 62, 85 per cent) than in C-G trials (44 of 64, 69 per cent). Further analysis (Manetl-Naenszel test) showed the over-all difference in outcome to be significant (P = 0.049), but the general applicability of this result may be limited by the rather low incidence of gram-negative bacterial infections in this study. There was no difference between the treatment regimens in antibiotic toxicity, and serious superinfection occurred only in group 2 patients (21 per cent of trials), equally divided between treatment arms. Initial protocol dosing achieved target plasma levels of trimethoprim (3 to 8 micrograms/ml) or gentamicin (4 to 10 micrograms/ml) in 57 of 68 (84 per cent) C-T/S trials compared to 21 of 60 (35 per cent) C-G trials.

Adult↗
PubMed1980

The value of fungal surveillance cultures as predictors of systemic fungal infections.

Fungal surveillance cultures consisting of urine, stool, and respiratory specimens were analyzed from 37 recipients of bone-marrow transplants and 52 patients undergoing chemotherapy for acute leukemia and other hematologic malignancies. All patients had prolonged aplasia. Sixty-seven percent of the patients were colonized by Candida albicans, and 28% were colonized by Candida tropicalis. No patient was colonized with any species of Aspergillus. There were 21 proven systemic fungal infections: three due to C. albicans, 16 due to C. tropicalis, and two due to Aspergillus. Positive surveillance data for C. tropicalis correlate with disease. Multiple positive-culture data yielded high predictive values (67%-83%), and single positive-culture data yielded slightly lower values as a function of body site. Positive surveillance data for C. albicans did not correlate with disease; negative culture data correlate with the absence of systemic disease due to C. tropicalis and C. albicans. Thus, surveillance data for specific fungal species can aid in diagnosis and appropriate therapy.

Aspergillus↗
PubMed1980

Incidence of polyene-resistant yeasts recovered from clinical specimens.

The development of resistance to amphotericin B and nystatin in yeast isolates was determined. Organisms recovered from patients on the oncology service, undergoing extensive chemotherapy for acute leukemia and bone marrow transplantation, were compared with yeasts recovered from patients on other services in the same hospital over a 7-month period. An agar dilution method was used to assay the susceptibility for each antibiotic; resistance was defined as a minimal inhibitory concentration of greater than or equal to 2 micrograms/ml for amphotericin B and greater than or equal to 16 micrograms/ml for nystatin. None of 625 isolates from 238 patients on non-oncology services demonstrated polyene resistance. Resistance only occurred in a subpopulation of oncology patients, in which 55 isolates (7.4%) from six patients (8.6%) exhibited polyene resistance. Resistance yeasts included Candida albicans (three strains), Candida tropicalis (one strain), and Torulopsis glabrata (two strains). All of the patients from whom resistant yeasts were recovered had experienced extensive chemotherapy with cytotoxic agents, granulocytopenia, and long-term treatment with both antibacterial and polyene antibiotics. Resistance to 2 micrograms of amphotericin B per ml and to 16 micrograms of nystatin per ml was associated with loss or marked depression of ergosterol in the cell membrane as measured by ultraviolet spectra. A significant incidence of polyene resistance in an oncology subpopulation was documented, suggesting a need for susceptibility testing in patients who are at high risk for development of drug-resistant fungal pathogens.

Amphotericin B↗
PubMed1980

Pathogenicity of Candida tropicalis and Candida albicans after gastrointestinal inoculation in mice.

The ability of clinical isolates of Candida albicans and candida tropicalis to invade through normal and damaged gastrointestinal mucosa was determined. Adult mice were treated with either gentamicin or gentamicin and cytarabine. Suspensions of yeast cells (10(7)) were administered through a catheter intraesophageally. Invasion was determined by culturing liver, kidney, and lung tissue from mice sacrificed after 48 h. C. albicans and C. tropicalis were incapable of invading through normal gastrointestinal mucosa in mice treated only with gentamicin. Two isolates of C. tropicalis penetrated the damaged gastrointestinal mucosa in 69% (49 of 71) of mice treated with gentamicin and cytarabine. In contrast, three isolates of C. albicans penetrated he damaged gastrointestinal mucosa in only 23% (14 of 62) of mice. These results suggest that C. tropicalis is more capable of invading through damaged gastrointestinal mucosa than C. albicans. The observations in this mouse model parallel those seen in patients on cytotoxic drugs. Therefore, this model offers a tool for investigation of the pathogenicity of these organisms in a model analogous to the compromised host.

Animals↗
PubMed1979

Deafness and Waldenström's macroglobulinemia.

Neurologic abnormalities are known to occur in a significant number of patients with Waldenström's macroglobulinemia. We have described such a patient whose initial presenting symptom was sudden hearing loss. She had no progression of the hearing deficit with long-term anticoagulant therapy.

Female↗
PubMed1979

Pulmonary interstitial changes following bone marrow transplantation.

Observations of 20 consecutive bone marrow transplantation recipients disclosed two distinctive categories of pulmonary interstitial changes. Interstitial infiltrates occurring less than 14 days after transplantation were observed in 13 of 20 patients and are believed to represent pulmonary edema. A late pulmonary interstitial process, which appears more than 30 days following transplantation (median 57 days), was encountered in 10 of 14 patients with successful grafts; the late changes represent interstitial pneumonia, a common cause of morbidity and mortality following bone marrow transplantation. It is probably attributable to a combination of factors including the preparatory chemotherapy and radiotherapy, and delayed immunologic reconstitution following transplantation.

Adult↗
PubMed1979

Candida tropicalis: a major pathogen in immunocompromised patients.

Of 89 consecutive patients undergoing treatment for hematologic malignancies or undergoing allogeneic bone marrow transplantation, 60 were colonized with Candida albicans and 25 with C. tropicalis. However, of the 18 disseminated infections caused by Candida species, 15 infections in 14 patients were caused by C. tropicalis and only three infections in three patients by C. albicans. The setting in which the infection occurred, skin lesions, polyarthralgias, or polymyalgias, and the unexplained deterioration of renal function were features suggestive of the diagnosis. Defervescence occurred in 10 of the 14 treated patients with C. tropicalis infections in 1 to 6 d (mean, 2.5 d) after initiation of therapy, even though all continued to be granulocytopenic. Resolution occurred in eight of the 15 C. tropicalis infections. In one case outcome was indeterminate, four patients died due to the infection, and two died from other causes but with the infection unresolved.

Adolescent↗