Prevention of corticosteroid-induced suppression of human polymorphonuclear leukocyte-induced damage of Aspergillus fumigatus hyphae by granulocyte colony-stimulating factor and gamma interferon.

Neutrophils (PMNs) are a critical line of defense against Aspergillus fumigatus infection. Increased frequency of invasive aspergillosis has been observed in patients receiving corticosteroids, suggesting a deleterious effect of these compounds on PMN antifungal function. To investigate this hypothesis and to determine the potential preventive utility of granulocyte colony-stimulating factor (G-CSF) and gamma interferon (IFN-gamma), the effects of hydrocortisone (HCS) and dexamethasone (DXS) on PMN-induced damage of Aspergillus fumigatus hyphae were studied with or without pretreatment of PMNs with G-CSF and IFN-gamma.

Perspectives on the use of cytokines in the management of infectious complications of cancer.

Treatment of neoplastic diseases is followed by a variety of infectious complications. Neutropenia and functional defects of phagocytes are common consequences of cancer and its treatment and contribute to an increased susceptibility to infections. Cytokines with hematopoietic growth stimulatory and/or immunoenhancing properties, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interleukin-3, interferon-gamma, macrophage colony-stimulating factor, interleukin-1, and interleukin-6 have been shown to either have clinical utility in patients with cancer and neutropenia or offer the promise to do so.

Ontogenesis of chick iris intrinsic muscles: evidence for a smooth-to-striated muscle transition.

The iris sphincter muscle consists of striated muscle fibers in the adult chicken. The ontogenetic development of this muscle has been studied by immunocytochemistry, from Embryonic Day 7 to the time of hatching. The time course of expression of specific markers of either smooth or striated muscle, i.

Management of the cancer patient with fever and prolonged neutropenia.

Cancer patients who suffer prolonged durations of fever and neutropenia are at high risk for developing serious infections. This article reviews the initial management of these fevers, subsequent modifications of the initial empirical regimens (both empirical changes in the antibiotic regimen and those changes directed at specific sites of infection that may become apparent during the course of prolonged neutropenia), and the potential impact of hematopoietic cytokines on future management of prolonged fever and neutropenia.

The prevalence of computed tomographic abnormalities of the cerebrum in 100 consecutive children symptomatic with the human immune deficiency virus.

Qualitative analysis of 100 consecutive computed tomographic (CT) studies of the brain in children with symptomatic but untreated acquired immunodeficiency syndrome was performed. After excluding children with associated medical illnesses that might confound the diagnosis of encephalopathy or alter brain structure, an abnormality of at least one of the measures of ventricular size, cortical atrophy, white matter attenuation (leukoaraiosis), or cerebral calcification was found in 86% of the patients studied. Ventricular enlargement was the most common abnormality, followed by cortical atrophy, leukoaraiosis, and cerebral calcification.

Lysis-centrifugation blood cultures in the detection of tissue-proven invasive candidiasis. Disseminated versus single-organ infection.

Several studies have demonstrated significantly higher frequency and more rapid detection of candidemia with blood culture methods performed by lysis-centrifugation (LC) in comparison with other techniques. Little is known, however, about the ability of LC blood culture methods to detect tissue-proven invasive candidiasis. We therefore investigated the sensitivity of LC blood cultures in the detection of tissue-proven invasive candidiasis.

Biologicals and hematopoietic cytokines in prevention or treatment of infections in immunocompromised hosts.

The number of immunocompromised hosts has dramatically increased in recent years. The primary reason for this increase has been the intensification of antineoplastic therapy for the treatment of various malignancies and the explosive spread of human immunodeficiency virus infection. Although the treatment and prevention of many infections have been improved with the rational use of antimicrobial agents, ultimate success can be blunted by protracted impairment of essential host defenses or by the virulence of certain organisms.

High-level resistance to zidovudine but not to zalcitabine or didanosine in human immunodeficiency virus from children receiving antiretroviral therapy.

Human immunodeficiency virus type 1 (HIV-1) isolates from children receiving long-term therapy with an alternating regimen of zidovudine and zalcitabine, or with didanosine monotherapy, were evaluated for resistance to zidovudine, zalcitabine, and didanosine, and for mutations known to be associated with zidovudine or didanosine resistance. HIV-1 from four of six patients receiving zidovudine with zalcitabine developed high-level resistance to zidovudine. A mutation in the HIV-1 reverse transcriptase that is highly associated with zidovudine resistance was identified in all four zidovudine-resistant posttherapy isolates.

Oxidized ATP. An irreversible inhibitor of the macrophage purinergic P2Z receptor.

The effects of oxidized ATP (oATP) on responses triggered by extracellular adenosine 5'-triphosphate (ATPe) were investigated in the mouse macrophage-like cell line J774. ATPe induced in this cell line two kinds of responses mediated by two different P2 purinergic receptors: 1) an early permeabilization of the plasma membrane to extracellular hydrophilic markers of M(r) up to 900 mediated by P2Z receptors; and 2) a fast mobilization of Ca2+ from intracellular stores mediated by P2Y receptors. Low oATP concentrations (100 microM) completely blocked the first response without affecting the second.

Impairment of neutrophil antifungal activity against hyphae of Aspergillus fumigatus in children infected with human immunodeficiency virus.

Human immunodeficiency virus (HIV)-infected patients may acquire invasive aspergillosis without previously recognized risk factors, such as neutropenia or corticosteroid therapy. Because neutrophils (PMNL) are an important component of host defense in aspergillosis, the antifungal activity of PMNL against hyphae of Aspergillus fumigatus in 31 HIV-infected children was assessed. Hyphal damage was unaffected in 15 HIV-infected children with age-adjusted CD4 cell counts > or = 25% of the normal median value; it was decreased in 16 with CD4 cell counts < 25% (both vs.

Pancreatitis in human immunodeficiency virus-infected children receiving dideoxyinosine.

To define predictive or contributory risk factors for pancreatitis in human immunodeficiency virus-infected children receiving dideoxyinosine (ddI), the authors evaluated 95 children, 3 months to 18 years of age, who had received ddI at 60 to 540 mg/m2 per day for a mean of 56 weeks. Pancreatitis developed in 7 patients (7%) but resolved in all upon withdrawal of ddI. Neither age, sex, nor CD4 count at study entry was predictive of pancreatitis, but pancreatitis appeared more likely to develop in hemophiliacs than in other patients (4 of 23 vs 3 of 72).

Enhancement of oxidative response and damage caused by human neutrophils to Aspergillus fumigatus hyphae by granulocyte colony-stimulating factor and gamma interferon.

Invasive aspergillosis is a serious fungal infection caused by the proliferation and invasion of Aspergillus hyphae in tissue. Neutrophils (PMNs) are the most important line of defense against Aspergillus hyphae. To investigate the role of granulocyte colony-stimulating factor (G-CSF) and gamma interferon (IFN-gamma) against Aspergillus fumigatus, we studied the effects of the two cytokines on the oxidative burst and the capacity of normal human PMNs to damage hyphae of the organism.

Suppression of polymorphonuclear leukocyte bactericidal activity by suramin.

Suramin is a polyanionic compound with potent antineoplastic properties. Because polymorphonuclear leukocytes (PMNs) are a crucial component of host defenses against bacteria and fungi, the effects of suramin on PMN function were studied in vitro. PMNs from healthy donors were incubated with concentrations of suramin of 1 to 1,000 micrograms/ml (within and exceeding the therapeutic range) for 30 min, and PMN functional parameters were subsequently assessed.

Human immunodeficiency virus (HIV) type 1 strain MN neutralizing antibody in HIV-infected children: correlation with clinical status and prognostic value.

Protective immunity to human immunodeficiency virus (HIV) was examined in 228 serial sera from 58 HIV-infected children before and during antiretroviral therapy. Binding antibodies to putative protective V3 epitopes of HIV-1IIIB and HIV-1MN were investigated by a peptide ELISA, and neutralizing antibodies by inhibition of HIV-1MN cell-free viral infection. No difference in binding of total IgG or IgG subclasses was observed between patients with mild (group A) or advanced disease (group B).

Successful surgical management of neutropenic enterocolitis in two patients with severe aplastic anemia. Case reports and review of the literature.

We describe two patients with severe aplastic anemia in whom neutropenic enterocolitis developed while they were undergoing treatment at the National Institutes of Health. Both patients had progressive symptoms while receiving optimal medical management and both underwent and survived surgical intervention despite continued prolonged neutropenia in the perioperative period. This experience contrasts with six cases reported in the literature and suggests that surgery can be employed even in patients with profound neutropenia.

Fever and granulocytopenia in children with cancer: a study of 299 episodes with two treatment protocols in Brazil.

In Brazil, 226 children with cancer presenting 299 episodes of fever and neutropenia (< or = 500/mm3) were treated with two consecutive empirical regimens. Regimen I-Cefoxitin Amikacin-Carbenicillin; and Regimen II Ceftriaxone-Amikacin. 67.

Approach to the patient with prolonged granulocytopenia.

In most centers treating cancer patients, significant progress has been made in permitting patients to survive even prolonged courses of neutropenia. This has resulted from a better understanding of the epidemiology of infection and the points during the clinical course when they pose a risk for the patient with prolonged neutropenia. Considerable benefit has been derived from the availability of more potent broad-spectrum antimicrobial agents and from organized strategies for when they should be initiated, how and when they should be modified, and for how long they should be continued.

Characterization of the cytotoxic effect of extracellular ATP in J774 mouse macrophages.

Extracellular ATP (ATPo) is known to be cytotoxic to many cell types through a mechanism which is largely unknown. Very recently this nucleotide has been shown to cause cell death by apoptosis, probably by interacting with specific cell-surface receptors. In the present study we have investigated the mechanism of ATPo-dependent cytotoxicity in the macrophage-like mouse cell line J774.

A prospective randomized trial comparing the infectious and noninfectious complications of an externalized catheter versus a subcutaneously implanted device in cancer patients.

Purpose: To compare the frequency of infectious episodes or other problems occurring with an externalized catheter (Hickman) versus a subcutaneously implanted device (Port-a-Cath, Pharmacia, Piscataway, NJ) in cancer patients, we performed a prospective, randomized study in 100 cancer patients (age range, 5 to 74 years).

Patients And Methods: Patients who were chemotherapy candidates and required an indwelling catheter were monitored prospectively and evaluated during the 180 days after the insertion of the catheter and again at time of study closure. The frequency of catheter use, reason for access, and any problems that might have been related to catheter use were noted.

Cerebral artery aneurysms in children infected with human immunodeficiency virus.

More than 250 children treated at our institution on antiretroviral treatment protocols have been monitored with brain imaging studies. We documented the occurrence and progression of aneurysms of major cerebral arteries in two children with advanced human immunodeficiency virus infection. In both cases these lesions remained clinically silent initially, despite progression to marked dilation.

Role of P2z purinergic receptors in ATP-mediated killing of tumor necrosis factor (TNF)-sensitive and TNF-resistant L929 fibroblasts.

Two closely related cell lines were characterized in their responses to extracellular ATP (ATPo): the fibroblast cell line L929 and a TNF-resistant variant L929/R. Both lines showed ATPo-activated increases in intracellular Ca2+, inward current, and sustained depolarization of the plasma membrane, cell responses compatible with activation of purinergic receptors of the P2y, P2x, or P2z subtype; however, only the L929/R variant was susceptible to ATPo-dependent early permeabilization of the plasma membrane to hydrophilic solutes of M(r) below 900, a response uniquely caused by the activation of P2z receptors. Both cell types were susceptible to the cytotoxic effect of ATPo, but killing of the L929/R variant required much shorter incubations in the presence of this nucleotide.