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Biomedical subjects

C U Tuazon

Publications and source records attributed to C U Tuazon.

At least 19 recordsLinked to original sources
PubMed1992

Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group.

BACKGROUND: Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS). Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease. METHODS: In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis. Eligible patients, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period. RESULTS: Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34). Treatment was successful in 25 of the 63 amphotericin B recipients (40 percent; 95 percent confidence interval, 26 percent to 53 percent) and in 44 of the 131 fluconazole recipients (34 percent; 95 percent confidence interval, 25 percent to 42 percent) (P = 0.40). There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 [14 percent] vs. 24 of 131 [18 percent]; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25). The median length of time to the first negative cerebrospinal fluid culture was 42 days (95 percent confidence interval, 28 to 71) in the amphotericin B group and 64 days (95 percent confidence interval, 53 to 67) in the fluconazole group (P = 0.25). Multivariate analyses identified abnormal mental status (lethargy, somnolence, or obtundation) as the most important predictive factor of a high risk of death during therapy (P less than 0.0001). CONCLUSIONS: Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS. Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure. The optimal therapy for patients at high risk remains to be determined.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Migration of 75Se-methionine-labeled Schistosoma japonicum in normal and immunized mice.

The patterns of migration and attrition of Schistosoma japonicum larvae were studied in a mouse model. Control and immunized mice were challenged with 100 S. japonicum cercariae tagged with 75Se-labeled methionine. Skin, lungs, liver, and other organs were analyzed by compressed organ autoradiography for the presence of larvae that appeared as reduced silver foci. The pattern of migration of S. japonicum was similar in mice with primary infection and in mice immunized with irradiated cercariae. Skin was not a site of attrition after primary infection nor after immunization. Attrition occurred after migration to the lungs and continued until after migration to the liver in mice with primary infection, while in immunized mice attrition occurred before lung migration and continued at a faster rate than in normal mice. In both control and immunized mice, the lungs and liver were the major sites of attrition.

Animals↗
PubMed1992

Disseminated histoplasmosis with unusual cutaneous lesions in a patient from the Philippines.

The incidence and prevalence of histoplasmosis in Southeast Asia has not been extensively described. The first microbiologically documented case of disseminated histoplasmosis with cutaneous papulonodules in a 56-year-old woman from the Philippines is reported. She presented with fever and generalized papulonodular lesions in various stages, which evolved into vesicles with central necrosis that resembled molluscum contagiosum with an indurated erythematous halo. Biopsies revealed a granulomatous mass of lymphohistiocytic and epithelioid cells with intracellular budding yeast cells and dark nuclei. Cultures were positive for Histoplasma capsulatum. The patient was treated with amphotericin B (3 g) and 5-fluorocytosine (50 mg/kg/day), followed by ketoconazole (400 mg/day). Her clinical course was complicated by intractable hemolytic anemia that was initially treated with corticosteroids. A splenectomy was subsequently performed. Pneumonia and a brain abscess caused by Nocardia asteroides were secondary complications. Nine months after her admission, repeat testing was diagnostic for systemic lupus erythematosus. This patient serves to re-emphasize that cutaneous lesions in an immunocompromised patient must be evaluated by biopsy and culture analysis. Disseminated histoplasmosis in the immunocompromised host may present with unusual cutaneous lesions, and must be considered even in a nonendemic area.

Amphotericin B↗
PubMed1991

Disseminated intravascular coagulation associated with Staphylococcus aureus septicemia is mediated by peptidoglycan-induced platelet aggregation.

Disseminated intravascular coagulation (DIC) may complicate severe septicemia caused by Staphylococcus aureus. S. aureus can induce spontaneous platelet aggregation in vitro, the rapidity and degree of which correlates with the severity of DIC in patients with sepsis. Purified peptidoglycan from DIC isolates aggregated human platelets in the presence of staphylococcal protein A with significantly shorter aggregation times than did peptidoglycan from non-DIC isolates. Purified teichoic acid from DIC and non-DIC isolates failed to aggregate platelets in vitro, or in vivo in guinea pigs but inhibited the peptidoglycan-induced aggregation in a dose-response manner. These studies suggest that peptidoglycan may mediate S. aureus-induced spontaneous platelet aggregation in vitro and DIC in vivo. The variability among strains of S. aureus to induce DIC and platelet aggregation may depend on the unique composition of their peptidoglycan and perhaps also the extent of exposure or availability of cell wall teichoic acid.

Animals↗
PubMed1991

An HLA-C-restricted CD8+ cytotoxic T-lymphocyte clone recognizes a highly conserved epitope on human immunodeficiency virus type 1 gag.

A unique epitope on the gag protein of human immunodeficiency virus type 1 (HIV-1), located at amino acid 145 to 150, has been mapped by using a CD8+ cytotoxic T-lymphocyte (CTL) clone. This epitope is highly conserved among 18 HIV-1 strains. The HIV-1 gag-specific human leukocyte antigen (HLA) class I-restricted CD8+ CTL clone was generated from fresh peripheral blood mononuclear cells of an HIV-seropositive donor by stimulation with gamma-irradiated allogeneic peripheral blood mononuclear cells in the presence of an anti-CD3 monoclonal antibody and recombinant interleukin-2. This gag-specific CTL clone killed autologous target cells infected with a recombinant vaccinia virus containing the gag gene of HIV-1 and target cells pulsed with an authentic p24gag construct expressed in Escherichia coli. Fine specificity was determined by using a panel of overlapping 30-amino-acid-long synthetic peptides and subsequently using smaller peptides to precisely map the CTL domain on p24. The epitope is on a highly conserved region, and it overlaps with a major B-cell epitope of gag. This CD8+ T-cell epitope is restricted by HLA-Cw3, which has not been previously identified as a restricting element for human CTL responses.

Amino Acid Sequence↗
PubMed1990

Trimetrexate-leucovorin dosage evaluation study for treatment of Pneumocystis carinii pneumonia.

To determine the maximal tolerable dosage of trimetrexate for treatment of pneumocystis pneumonia, 25 patients were treated each day with 45 mg/m2 of trimetrexate and 80 mg/m2 of leucovorin; 10 received 60 mg/m2 and 80 mg/m2; 12 received 60 mg/m2 and 160 mg/m2; and 6 received 90 mg/m2 and 160 mg/m2, respectively. Leucovorin was increased twofold and trimetrexate reduced by 50% or suspended briefly for various levels of neutropenia and thrombocytopenia until blood counts increased. Dosage-modifying hematologic toxicity occurred in 12 (46%), 8 (80%), 9 (75%), and 4 (67%) patients with the respective groups. Cytopenias were in each case reversible and other toxicities were well tolerated. All survivors but one were able to receive a full 21 doses of trimetrexate. Twenty-four (92%), 10 (100%), 7 (58%), and 4 (80%) of patients in the respective groups survived. Thus, the 45 mg/m2/day dosage of trimetrexate with 80 mg/m2/day of leucovorin resulted in the least dosage-modifying toxicity and excellent efficacy. This combination should be selected for studies to compare trimetrexate with other therapies for pneumocystis pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Toxoplasmosis in AIDS patients.

In patients with AIDS, toxoplasmosis is the most common cause of CNS mass lesions. Diagnosis is made on the basis of clinical presentation and CAT scan findings and confirmed by demonstration of tachyzoites and/or cysts in tissues obtained by needle aspiration or brain biopsy. Response to therapy with pyrimethamine and sulphadiazine is usually prompt but therapy has to be continued for the lifetime of AIDS patients with CNS toxoplasmosis. To date, no alternative regimens of single or combination drugs appear to be effective in patients who fail, or are unable to tolerate pyrimethamine and sulphadiazine therapy. Relapse rate is high. Clearly, there is a need to organize prospective controlled studies to assess the role of agents such as clindamycin, trimetrexate and other drugs in the treatment of CNS toxoplasmosis in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry.

Monocytes and macrophages, which may play a central role in the pathogenesis of infection with human immunodeficiency virus type 1 (HIV-1), express the CD4 molecule and Fc receptors (FcR) for immunoglobulin G (IgG). To explore the possibility that FcR mediate HIV-1 infection of monocytes, studies were conducted with the human monocytic cell line U937. These cells were exposed to HIV-1 complexed with various concentrations of serum from HIV-1 antibody-positive individuals and monitored for HIV-1 replication. Serum samples from antibody-negative normal individuals did not affect virus yields. High concentrations of antibody-positive sera showed virus-neutralizing activity; however, cells infected with HIV-1 in the presence of antibody-positive sera at subneutralizing concentrations significantly enhanced virus replication. This infection enhancement was blocked by heat-aggregated gamma-globulin. Moreover, the IgG fraction from an HIV-1 antibody-positive serum enhanced HIV-1 infection at the same serum dilution equivalents. In contrast, IgG-F(ab')2 did not enhance HIV-1 infection but showed neutralizing activity with HIV-1. These results are compatible with the concept of FcR-mediated infection enhancement and suggest that this immunological response to HIV-1, instead of protecting the host, potentially facilitates the infection.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Treatment of Pneumocystis carinii pneumonia with trimetrexate in acquired immunodeficiency syndrome (AIDS).

In vitro studies have shown that trimetrexate, a lipid-soluble analogue of methotrexate, is 1500 times more potent than trimethoprim as an inhibitor of dihydrofolate reductase from Pneumocystis carinii. Furthermore, trimetrexate is readily taken up by P carinii, while performed folates such as leucovorin are not. These observations suggest that the combination of trimetrexate plus leucovorin, which can specifically protect mammalian host tissues from the toxic effects of the antifolate, may be useful in the treatment of pneumocystis pneumonia. This concept was tested in a clinical study of 49 patients with acquired immunodeficiency syndrome (AIDS) and P carinii pneumonia who were treated for 21 days with trimetrexate and leucovorin. Patients were divided into three groups: 16 patients who were unable to tolerate or had failed both pentamidine isethionate and trimethoprim-sulfamethoxazole therapy were treated with trimetrexate plus leucovorin (Group I); 16 patients who were unable to tolerate sulfonamide therapy were treated with trimetrexate with leucovorin as initial therapy (Group II); and 17 patients in whom trimetrexate with leucovorin plus sulfadiazine was used as initial therapy (Group III). Response and survival rates were 69% and 69% in Group I; 63% and 88%, respectively, in Group II; and 71% and 76%, respectively, in Group III. Toxicity was minimal. The results indicate that trimetrexate with leucovorin is safe and effective for initial therapy in AIDS patients with P carinii pneumonia and in those intolerant or unresponsive to standard therapies.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Trimetrexate for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome.

Preclinical studies have demonstrated that trimetrexate is a potent inhibitor of dihydrofolate reductase from Pneumocystis carinii. On the basis of this evidence, this lipid-soluble antifolate was used as an antipneumocystis agent in 49 patients with the acquired immunodeficiency syndrome (AIDS) and pneumocystis pneumonia. Simultaneous treatment with the reduced folate leucovorin was used as a specific antidote to protect host tissues from the toxic effects of the antifolate without affecting the antipneumocystis action of trimetrexate. Patients were assigned to three groups and treated for 21 days: in Group I, trimetrexate with leucovorin was used as salvage therapy in patients in whom standard treatments (both pentamidine isethionate and trimethoprim-sulfamethoxazole) could not be tolerated or had failed (16 patients); in Group II, trimetrexate with leucovorin was used as initial therapy in patients with a history of sulfonamide inefficacy or intolerance (16 patients); and in Group III, trimetrexate with leucovorin plus sulfadiazine was used as initial therapy (17 patients). The response and survival rates were, respectively, 69 percent and 69 percent in Group I; 63 percent and 88 percent in Group II; and 71 percent and 77 percent in Group III. Trimetrexate therapy had minimal toxicity; transient neutropenia or thrombocytopenia occurred in 12 patients and mild elevation of serum aminotransferases in 4. We conclude that the combination of trimetrexate and leucovorin is safe and effective for the initial treatment of pneumocystis pneumonia in patients with AIDS and for the treatment of patients with intolerance or lack of response to standard therapies.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Teicoplanin and rifampicin singly and in combination in the treatment of experimental Staphylococcus epidermidis endocarditis in the rabbit model.

Teicoplanin and rifampicin were evaluated as single and combined agents in the treatment of endocarditis due to Staphylococcus epidermidis in the rabbit model. Rabbits were treated for ten days and the number of bacteria in vegetations determined. At the end of ten days the geometric mean number of bacteria in the vegetations were 5.53 X 10(8), 6.68 X 10(6). 1.10 X 10(4), 2.57 X 10(1) cfu/g of vegetation for control, teicoplanin, rifampicin, and teicoplanin plus rifampicin groups respectively. The MIC and MBC values of the S. epidermidis isolates were 0.78 mg/l for teicoplanin and less than or equal to 0.10 mg/l for rifampicin. In the rifampicin treated group three post-treatment isolates of S. epidermidis tested exhibited marked resistance to rifampicin with MIC and MBC values greater than or equal to 200 mg/l. Teicoplanin and rifampicin were both effective as single agents in the clearance of S. epidermidis from the bloodstream. Rifampicin was more effective than teicoplanin in the clearance of S. epidermidis from vegetations but teicoplanin in combination with rifampicin was more effective than either drug alone.

Animals↗
PubMed1987

Acid-fast smear and culture of respiratory secretions, bone marrow, and stools as predictors of disseminated Mycobacterium avium complex infection.

Disseminated infection caused by Mycobacterium avium complex (MAC) is common in patients with acquired immune deficiency syndrome and is difficult to treat because of the high degree of resistance to antimycobacterial agents. Early diagnosis and treatment may prolong survival of patients with acquired immune deficiency syndrome and MAC infection. Twenty patients with disseminated MAC infection were evaluated for recovery of the organism from bone marrow, bronchial washings or sputum, and stools before the organism was isolated in blood culture. For 40 to 67% of patients, MAC was recovered from these specimens before it was isolated in blood culture.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Management of infectious and immunological complications of acquired immunodeficiency syndrome (AIDS). Current and future prospects.

AIDS is caused by a newly recognised virus (human immunodeficiency virus; HIV) which induces a profound defect in cellular immune function associated with increased susceptibility to opportunistic infections and certain malignancies. The clinical presentation of HIV ranges from asymptomatic infection to severe immunodeficiency manifesting as severe life-threatening infectious diseases or malignancies. While major research efforts are being directed toward development of vaccine and discovery of effective antiretroviral drugs, clinicians are faced with AIDS patients with multiple and complicated medical problems including opportunistic infections and certain malignancies. Currently, efforts are directed toward early diagnosis, treatment, and prevention of recurrence of these opportunistic infections. The current approaches are reviewed in this article. Major recent developments in AIDS research include the isolation of the HIV on culture and the availability of the antibody test. Aside from vaccine and antiretroviral drugs, other measures that may be of benefit in the treatment of AIDS patients are immunological enhancement and reconstitution. Several studies are underway to evaluate antiviral agents in the treatment of HIV infection. Those undergoing clinical trial include suramin, ribavirin, antimoniotungstate, phosphonoformate and azidothymidine. Immune enhancers that have been used include alpha- and gamma-interferon and interleukin-2. HLA-matched lymphocyte transfusions and bone marrow transplantations have been used alone and in combination to replace the AIDS patient's defective immune system.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Toxoplasma encephalitis in patients with acquired immune deficiency syndrome: diagnosis and response to therapy.

Although Toxoplasma gondii is the most commonly recognized cause of central nervous system mass lesions in patients with acquired immune deficiency syndrome, published investigations have provided little information about criteria for diagnosis of toxoplasmosis or the response to therapy. In this series the method of diagnosis and response to therapy were assessed in 14 patients who had evidence for toxoplasmosis based on routine histopathology, immunoperoxidase staining, or mouse inoculation. These patients presented with clinical and radiologic findings that did not clearly distinguish them from patients with other infectious or neoplastic processes. Excisional biopsies usually showed tachyzoites on routine histology, but needle biopsies were usually negative unless mouse inoculation or immunoperoxidase staining was employed. Response to pyrimethamine and sulfadiazine therapy was often prompt, but therapy had to be continued for long periods of time to maintain a clinical response, and no alternative regimen of one or more drugs appeared to be effective in patients unable to tolerate both pyrimethamine and sulfadiazine.

Acquired Immunodeficiency Syndrome↗