Biomedical subjects

A Catanzaro

Publications and source records attributed to A Catanzaro.

At least 55 records · Page 3Linked to original sources

PubMed1995

Pentamidine aerosol versus trimethoprim-sulfamethoxazole for Pneumocystis carinii in acquired immune deficiency syndrome.

Pneumocystis carinii pneumonia remains one of the most common opportunistic infections in patients with acquired immune deficiency syndrome (AIDS). Treatment with either intravenous pentamidine or trimethoprim-sulfamethoxazole (TMP-SMX) is frequently complicated by serious adverse reactions. This study was a prospective, blinded comparison of 600 mg/d of pentamidine as an aerosol versus 15 mg/kg/d of trimethoprim plus 75 mg/kg/d of sulfamethoxazole for patients with mild or moderately severe P. carinii pneumonia (alveolar arterial oxygen difference of less than 55 mm Hg). Of 367 participants who were randomized to receive study therapies, 287 had proven and 16 had presumed Pneumocystis pneumonia. There were 29 deaths within 35 d of study initiation: 12 in the aerosolized pentamidine group and 17 in the TMP-SMX groups (log rank p = 0.28). The difference in mortality was 3.4% (95% CI = -3.5, 10.8%). Ninety-four patients treated with aerosolized pentamidine had to have their study therapy changed because of lack of efficacy, compared with 22 patients treated with TMP-SMX (p = 0.002). In addition PaO2 improved faster in patients treated with TMP-SMX. However, aerosolized pentamidine was discontinued less often than TMP-SMX because of toxicity (9.4 versus 40% p < 0.001). Rash (0.6 versus 14.9%), nausea and vomiting (1.7 versus 12.2%), and abnormalities of liver function tests (1.7 versus 12.2%) were the most common adverse effects necessitating treatment discontinuation. During 6-mo. follow-up there was no difference in mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗

PubMed1994

NIAID Mycoses Study Group Multicenter Trial of Oral Itraconazole Therapy for Invasive Aspergillosis.

BACKGROUND: Invasive aspergillosis is the most common invasive mould infection and a major cause of mortality in immunocompromised patients. Response to amphotericin B, the only antifungal agent licensed in the United States for the treatment of aspergillosis, is suboptimal. METHODS: A multicenter open study with strict entry criteria for invasive aspergillosis evaluated oral itraconazole (600 mg/d for 4 days followed by 400 mg/d) in patients with various underlying conditions. Response was based on clinical and radiologic criteria plus microbiology, histopathology, and autopsy data. Responses were categorized as complete, partial, or stable. Failure was categorized as an itraconazole failure or overall failure. RESULTS: Our study population consisted of 76 evaluable patients. Therapy duration varied from 0.3 to 97 weeks (median 46). At the end of treatment, 30 (39%) patients had a complete or partial response, and 3 (4%) had a stable response, and in 20 patients (26%), the protocol therapy was discontinued early (at 0.6 to 54.3 weeks) because of a worsening clinical course or death due to aspergillosis (itraconazole failure). Twenty-three (30%) patients withdrew for other reasons including possible toxicity (7%) and death due to another cause but without resolution of aspergillosis (20%). Itraconazole failure rates varied widely according to site of disease and underlying disease group: 14% for pulmonary and tracheobronchial disease, 50% for sinus disease, 63% for central nervous system disease, and 44% for other sites; 7% in solid organ transplant, 29% in allogeneic bone marrow transplant patients, and 14% in those with prolonged granulocytopenia (median 19 days), 44% in AIDS patients, and 32% in other host groups. The relapse rates among those who completed therapy and those who discontinued early for possible toxicity were 12% and 40%, respectively; all were still immunosuppressed. CONCLUSION: Oral itraconazole is a useful alternative therapy for invasive aspergillosis with response rates apparently comparable to amphotericin B. Relapse in immunocompromised patients may be a problem. Controlled trials are necessary to fully assess the role of itraconazole in the treatment of invasive aspergillosis.

AIDS-Related Opportunistic Infections↗

PubMed1994

Treatment of coccidioidomycosis with SCH 39304.

A new oral triazole antifungal, SCH 39304, was administered to 54 patients with progressive infections due to Coccidioides immitis from six collaborating centers. Patients were grouped according to site of infection including chronic pulmonary (25), bone/joint (17) and skin/soft tissue (12). The median age was 40 years; 83% were male, 52% white, 13% HIV-infected and 35% had failed previous therapy. The majority of patients were treated with either 100 mg or 200 mg day-1. One patient on renal dialysis received 300 mg day-1. Baseline abnormalities were reassessed for evidence of efficacy every 4 months and expressed in a standardized scoring system. Cumulative overall response rates at 4, 8 and 12 months were 7%, 36% and 66% respectively. Twelve month response rates by disease were 77% (pulmonary), 62% (skin/soft tissue) and 31% (bone/joint). Fifteen patients failed therapy although seven of these were still on treatment when the study was discontinued. Two failed due to toxicity. Possible symptoms or signs of toxicity occurred in 24 (44%) patients and were generally mild. SCH 39304 is an effective and well tolerated therapy for progressive forms of coccidioidomycosis.

Administration, Oral↗

PubMed1994

Antibodies to 68, 52, and 48 kd proteins of Mycobacterium avium in serum samples from patients with Mycobacterium avium infection.

Mycobacterium avium complex (MAC) is responsible for the highest incidence of disseminated bacterial infection in patients with AIDS. Disease caused by this organism was originally thought to be rare in nonimmunocompromised individuals, but it is now being encountered more frequently. Relatively little is known about the components that play a role in the immunopathology of infection caused by MAC. To identify the immunoreactive antigens of this organism that are important targets of the humoral immune response in MAC infection, serum samples from MAC-infected and non-MAC-infected patients were analyzed by Western Blot analysis with sonic extracts of M. avium (MA) as the antigen. The MAC-infected population included patients who were HIV-negative as well as patients with AIDS, and the non-MAC-infected population included non-AIDS, HIV-positive patients and normal, purified protein derivative-negative individuals. The immunodominant antigens recognized by the MAC-infected patients were the 68, 52, and 48 kd proteins of MA. These antigens were also recognized by a few of the non-MAC-infected patients. However, significant differences were observed between the number of MAC-infected and non-MAC-infected patients reacting with these antigens. Sixty-nine percent of the MAC-infected patient serum samples were found to react with the 68 kd antigen, whereas only 24% of the serum samples from patients without MAC infection recognized this antigen (p < 0.001). Of the MAC-infected serum samples, 53.1% were found to react with the 52 kd antigen, whereas only 22% of the non-MAC-infected patient serum samples reacted with this antigen (p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

PubMed1994

Identification of a 68 kd surface antigen of Mycobacterium avium that binds to human macrophages.

Infection caused by Mycobacterium avium is the major cause of bacteremia in patients with AIDS. A critical event in the initiation of a variety of bacterial infections is the adherence of bacteria to host cell surfaces, which is often brought about by the interaction of specific molecules on the bacterial surface with host cell surface receptors. In the present study, a sonicate of M. avium was used to isolate monocyte-binding proteins by affinity chromatography with CNBr-Sepharose-4B coupled to extracts of monocytes. A 68 kd protein present on the surface of M. avium was identified as one of nine monocyte-binding proteins. This protein was isolated and further characterized. The N-terminal amino acid sequence (22 residues) of the protein was determined and was found to exhibit strong homology with the 65 kd heat shock proteins of M. tuberculosis, M. leprae, and M. bovis. However, a previously characterized monoclonal antibody directed against a 66 kd antigen of M. avium was found to cross-react with the 68 kd protein from M. avium but not with the 65 kd proteins from M. leprae and M. bovis, suggesting that the 68 kd antigen may differ from the 65 kd proteins of M. leprae and M. bovis with respect to certain epitopes. In an in vitro inhibition assay, the 68 kd protein was found to compete with the attachment of intact fluorescein isothiocyanate-labeled M. avium to monocyte-derived macrophages, inhibiting this attachment in a dose-dependent manner up to 42%. The 65 kd proteins of M. leprae and M. bovis, on the other hand, did not appear to inhibit this attachment substantially (13.9% and 14.6%, respectively). These results suggest that the 68 kd protein of M. avium may be involved in binding to receptors on macrophages and help in the attachment of the organism to its host cell.

Amino Acid Sequence↗

PubMed1993

Fluconazole therapy for coccidioidal meningitis. The NIAID-Mycoses Study Group.

OBJECTIVE: To determine the efficacy and safety of fluconazole treatment of coccidioidal meningitis. DESIGN: Uncontrolled clinical trial. SETTING: Four university-based treatment centers in California, Arizona, and Texas. Most therapy was conducted without hospitalization. PATIENTS: Fifty consecutive patients with active coccidioidal meningitis, of which 47 (94%) were evaluable. Twenty-five patients had received no previous treatment for their meningitis, and nine had coinfection with human immunodeficiency virus (HIV). INTERVENTION: Fluconazole was administered in an oral dose of 400 mg once per day for up to 4 years (median, 37 months) in responding patients. Concurrent therapy with another antifungal agent was prohibited. MEASUREMENTS: Predefined assessment of infection-related abnormalities was done at the time of enrollment and was repeated at least every 4 months during treatment. Elimination of 40% or more of baseline abnormalities was considered a response. RESULTS: Thirty-seven of 47 (79%; 95% CI, 61% to 90%) evaluable patients responded to treatment. Response rates were similar for patients with and without previous therapy, for patients with and without concomitant HIV infection, and for patients with and without pre-existing hydrocephalus. Most improvement occurred within 4 to 8 months after starting treatment. Patient symptoms resolved more quickly than did cerebrospinal fluid abnormalities. In 15 of 20 responding patients followed for 20 months or more, residual low-level cerebrospinal fluid abnormalities remained throughout therapy. No patient discontinued therapy because of drug-related side effects, although confusion developed in two patients that resolved when the dose of fluconazole was reduced. CONCLUSION: Fluconazole therapy is often effective in suppressing coccidioidal meningitis.

AIDS-Related Opportunistic Infections↗

PubMed1993

Mycobacterium avium-M. intracellulare binds to the integrin receptor alpha v beta 3 on human monocytes and monocyte-derived macrophages.

Mycobacterium avium-M. intracellulare is an intracellular pathogen responsible for the highest incidence of disseminated bacterial infection in patients with AIDS. Treatment of the infection is difficult and has been of limited efficacy. Attachment of the organism to macrophages is a critical early step in the establishment of the disease. In the present study, we isolated and identified a receptor that mediates attachment of M. avium-M. intracellulare to human peripheral blood monocytes and monocyte-derived macrophages. On Western blotting, (immunoblotting), the receptor was found to cross-react with antibodies against a human vitronectin receptor (alpha v beta 3). The receptor could be purified from monocyte extracts by using monoclonal antibodies (MAbs) against the alpha v subunit of vitronectin receptor coupled to CNBr-Sepharose 4B, as well as with the adhesive tripeptide sequence arginine-glycine-aspartic acid (RGD) coupled to CNBr-Sepharose 4B. Surface-bound MAbs directed against alpha v beta 3 were found to inhibit the attachment of M. avium-M. intracellulare to monocyte-derived macrophages in an in vitro inhibition assay, while MAbs directed against CD14, CD18, alpha 2 beta 1 and platelet glycoprotein gpIIb/IIIa receptors did not inhibit this attachment. These observations suggest that alpha v beta 3 on the surface of human monocytes and monocyte-derived macrophages may function as a receptor for M. avium-M. intracellulare. Identification of a receptor for M. avium-M. intracellulare on macrophages may offer new approaches to the prevention and control of M. avium-M. intracellulare infection at the cellular level.

Amino Acid Sequence↗

PubMed1993

A rapid tuberculosis screening program for new mothers who have had no prenatal care.

We developed a Rapid Tuberculosis Screening Program for use in women who have not had prenatal care. All patients who presented for delivery without a documented tuberculin skin test (TBN-ST) were given a symptom questionnaire. Those who had a positive response to any of the questions received a chest roentgenogram to rule out active disease. All patients with a negative questionnaire had a TBN-ST soon after admission. The test was read at the time of discharge, whether or not 48 h had elapsed, and individuals who had 5 mm or more of induration at before 48 h and 10 mm or more induration at 48 to 72 h were considered reactors. Of 1,412 patients who received a TBN-ST, 259 were reactors. One case of active disease was diagnosed. Approximately 75 percent of "true" tuberculin reactors will be detected by this method. We suggest that by using the TBN-ST concurrently with a questionnaire, most patients infected with Mycobacterium tuberculosis can be identified.

Delivery, Obstetric↗

PubMed1992

Activity of defensins from human neutrophilic granulocytes against Mycobacterium avium-Mycobacterium intracellulare.

We have examined the activity of defensins from human neutrophilic granulocytes against Mycobacterium avium-Mycobacterium intracellulare. M. avium-M. intracellulare at 2.5 x 10(6)/ml or 2.5 x 10(8)/ml was cultured in the presence of defensins at 37 degrees C from 4 to 48 h. After incubation, CFU were enumerated. Human neutrophil peptide 1 (HNP-1) at 5 micrograms/ml had the ability to kill M. avium-M. intracellulare. Treatment with HNP-1 resulted in significant (96.3 to 97.7%) killing of M. avium-M. intracellulare, even after taking clumping into consideration. This activity was not affected by the presence of calcium (0.5 and 1.0 mM), magnesium (0.5 and 1.0 mM), or sodium chloride (25, 50, and 100 mM). The optimal pH for bactericidal activity was higher than 5. We tested numerous M. avium-M. intracellulare strains, and HNP-1 was successful in killing every strain, although the degree of killing varied among them (34.2 to 87.2%). Additionally, this activity was independent of colonial morphology. We also examined the activity of HNP-2 and HNP-3 against M. avium-M. intracellulare and found that they were as effective in killing M. avium-M. intracellulare as HNP-1 was. These observations suggest that defensins may play an important role in the host defense against M. avium-M. intracellulare.

Blood Bactericidal Activity↗

PubMed1992

Identification of a beta 1 integrin on Mycobacterium avium-Mycobacterium intracellulare.

Mycobacterium avium-Mycobacterium intracellulare (MAI) is an opportunistic intracellular pathogen responsible for the highest incidence of disseminated bacterial infection in patients with AIDS. Treatment of the infection is extremely difficult and has shown limited efficacy. A critical event in the initiation of a variety of bacterial infections involves the adherence of bacteria to host cell surfaces. In the present study, we have shown that MAI organisms bind avidly to extracellular matrix proteins such as laminin, collagen I, and fibronectin in an in vitro attachment assay. Immunoblot analysis of a sonicate of MAI with polyclonal antibodies against different integrin receptors indicated that the sonicate cross-reacts with polyclonal antibodies against a human laminin-binding integrin, alpha 3 beta 1, and a human fibronectin-binding integrin, alpha 5 beta 1, although it is reactive with only the beta 1 subunit in the case of both antisera. Antibodies against the alpha 3 beta 1 and alpha 5 beta 1 integrins specifically inhibited the binding of MAI to laminin, collagen I, and fibronectin by 70 to 97%, depending on the ligand, suggesting that the attachment of MAI to these extracellular matrix proteins may be mediated by a beta 1 integrin. Furthermore, the attachment of MAI to laminin, collagen I, and fibronectin was found to be cation dependent. MAI may use this and other beta 1-containing integrins to adhere and penetrate through basement membrane structures that underlie host cell linings. An understanding of the mechanism of attachment and a definition of the adhesive molecules on the surface of MAI may open up new approaches to the prevention of serious infection caused by this organism.

Bacterial Adhesion↗

PubMed1991

The response to human rIL-1, rIL-2, and rTNF in the middle ear of guinea pigs.

Human recombinant interleukin 1 (rIL-1), interleukin 2 (rIL-2), or tumor necrosis factor (rTNF) were injected transtympanically into the middle ear of normal guinea pigs. Effusion volume and cellular content were determined after sacrifice and rapid dissection of the ear. By 24 hours, rIL-2 (100 U) had produced a cellular effusion (77% to 92% polymorphonuclear neutrophil leukocytes), which cleared by 72 hours. rTNF (10 U) yielded a cellular effusion (12% to 67% lymphocytes) at 24 hours, which cleared by 48 hours. rIL-1 (100 U) did not produce significant effusion when compared to control. rIL-2 and rTNF cause an inflammatory effusion in the middle ear. To the extent they are generated in the middle ear during otitis media, these cytokines have the potential to contribute to the pathogenesis of otitis media with effusion.

Animals↗

PubMed1991

Diagnostic approach to Pneumocystis carinii pneumonia in the setting of prophylactic aerosolized pentamidine.

Recurrent Pneumocystis carinii pneumonia is common in patients with the acquired immunodeficiency syndrome who receive prophylaxis with aerosolized pentamidine. In this setting, the number of organisms is reduced and the clinical presentation may be altered. These observations have led to doubts regarding the use of induced sputum to diagnose PCP in patients receiving prophylactic AP. To determine if the examination of induced sputum is useful for patients receiving prophylactic AP, we examined our results over a 12-month period. We also examined several clinical criteria to ascertain if they could predict the likelihood of a positive induced sputum. As assessed by P(A-a)O2, need for admission and mortality, patients receiving AP presented with less severe disease than those not receiving AP. Twelve of 19 (63 percent) patients who developed PCP while receiving prophylactic AP were diagnosed by induced sputum. Induced sputum was positive for 35 of 55 (64 percent) patients who developed PCP and had not been receiving AP. However, there were no clinical characteristics which predicted a positive induced sputum. We conclude that induced sputum is an effective method for diagnosing PCP in patients receiving prophylactic AP.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Binding of Mycobacterium avium-Mycobacterium intracellulare to human leukocytes.

We examined nonopsonic binding of Mycobacterium avium-Mycobacterium intracellulare (MAI) by human leukocytes. Macrophages (M phi) avidly bound fluorescently labeled MAI in the absence of serum proteins. Binding appeared to be mediated by a lineage-specific, proteinaceous receptor on M phi, since (i) binding of labeled bacteria could be competitively inhibited by unlabeled MAI, (ii) treatment of M phi with trypsin ablated the ability of M phi to bind MAI, and (iii) the capacity to bind MAI was observed on monocytes, M phi, and stimulated polymorphonuclear cells but not on lymphocytes or unstimulated polymorphonuclear cells. The receptor for MAI appeared mobile in the plane of the membrane, since spreading of M phi on a carpet of immobilized, unlabeled MAI down modulated binding of labeled MAI added in suspension. The receptor required neither calcium nor magnesium for activity and appeared different from other known receptors for intracellular pathogens.

Binding Sites↗

PubMed1990

Fluconazole in the treatment of persistent coccidioidomycosis.

Fluconazole is one of the new antifungal triazoles undergoing clinical trials. We used fluconazole at a dose of 50 or 100 mg/day in an open trial for the treatment of patients with persistent coccidioidomycosis. Fourteen patients were enrolled and treated for a mean of 13 +/- 7 months. Two failed to respond. Of the 12 who responded, one reactivated while being treated, and one died of myocardial infarction after successful treatment of his fungal infection; six had relapses from nine days to 15 months after treatment was stopped. Only four patients are asymptomatic at a mean of 14 +/- 3 months after cessation of treatment. Fluconazole is well tolerated at this dose. In view of its low toxicity, the partial clinical efficacy observed, and the high recurrence rate of chronic coccidioidal infection, it would be justified to try higher doses.

Adult↗

PubMed1990

Pulmonary surfactant suppresses the immune lung injury response to inhaled antigen in guinea pigs.

Pulmonary surfactant (PS) has been shown to regulate the function of macrophages, T cells, B cells, and NK cells in vitro. We designed this study to explore the immunoregulatory role of PS in vivo. Guinea pigs were immunized to complete Freund's adjuvant (CFA) and 2 weeks later were subjected to an aerosol challenge with purified protein derivative (PPD) to induce immune lung injury (group I). Group II and group III were subjected to lung lavage by tracheostomy just before aerosol challenge. Group II was lavaged with 0.9% NaCl, which depleted PS by 32%. Group III was lavaged with 0.9% NaCl containing bovine surfactant, which did not alter total PS content. Control animals for each condition were not presensitized to CFA. All guinea pigs were killed 24 hours after the aerosol challenge; for each group n = 10 +/- 2. Bronchoalveolar lavage (BAL) protein and mononuclear leukocyte counts, as well as lung histopathologic grading, were performed. Group I animals showed evidence of mild immune lung injury by these parameters. Animals partially depleted of PS (group II) showed more severe lung injury with greater abnormalities in BAL leukocytes and histopathology compared with group I. Guinea pigs lavaged with fluid containing bovine surfactant (group III) were nearly identical to group I with respect to these two parameters. BAL protein levels were not related to PS depletion. This study suggests that surfactant may have an in vivo role in modulating the inflammatory response that accompanies immune lung injury in this model.

Aerosols↗

PubMed1988

Fluconazole penetration into cerebrospinal fluid in humans.

One hour after intravenous doses of 50 mg/d fluconazole for 6 days or 100 mg/d for seven days to healthy subjects, the cerebrospinal fluid concentrations of fluconazole were 1.26 mg/L and 2.74 mg/L, respectively. These values were approximately 52% and 62% those of serum. Four patients with an initial clinical diagnosis of meningitis also had significant concentrations of fluconazole in the cerebrospinal fluid.

Fluconazole↗

PubMed1988

Immunomodulation by pulmonary surfactant.

Canine pulmonary surfactant is recognized to modulate both T and B cell response in vitro. Because both responses involve cell proliferation, it has been suggested that surfactant interferes with the proliferation of lymphocytes. We herein report studies using human surfactant collected from amniotic fluid (HAFS). HAFS inhibited the proliferative response of human lymphocytes to antigen (PPD) and to allogeneic lymphocytes. Inhibition was linear within the dose range examined. Inhibition of the response to phytohemagglutinin was only evident when suboptimal doses of phytohemagglutinin were used. The effect of HAFS on the lysis of K562 human myeloid target cells by natural killer (NK) cells was also studied. Lysis in this system does not require proliferation. HAFS inhibited NK cell-induced lysis by 70% (250 micrograms HAFS per milliliter) to 95% (500 micrograms HAFS per milliliter). Inhibition was evident whether the cells were incubated with HAFS for 4 hours or for 18 hours. The NK suppressor activity was contained in the lipid fraction of HAFS, whereas the protein fraction revealed little activity. The washout experiments demonstrated that the action of HAFS was on NK cells and not on target cells. The immunomodulatory properties of surfactant affect NK cell activity and the proliferative response. Surfactant may protect the lungs from inappropriate immune reactions. Abnormalities of the lipid fraction of surfactant should be considered in studies of the mechanism of pulmonary diseases characterized by local pulmonary immune responses.

Amniotic Fluid↗

PubMed1987

Sequence of bronchoalveolar lavage and histopathologic findings in rat lungs early in inhalation asbestos exposure.

To assess the early cellular inflammatory response of the lungs, 7 rats per group were exposed nose-only to 13 mg/m3 of chrysotile asbestos, 7 h/day for 2, 4, or 6 wk. Lung histopathology and bronchoalveolar lavage (BAL) were analyzed. In exposed animals, dose-related bronchiolitis and fibrosis were found that were not seen in control rats (p less than 0.001). In exposed rats, total BAL cells were increased six-to sevenfold over matched controls, and more cells were retrieved with longer exposure (p less than 0.001). In the BAL, counts of macrophages, lymphocytes, and polymorphonuclear cells (PMNs) were each elevated in the exposed rats (each p less than 0.001). PMNs seen histologically and in the BAL may be related to the time period examined. PMNs and lymphocytes observed throughout this 6-wk study support the idea that these cells may have an important role in the early events of asbestos lung injury.

Administration, Inhalation↗