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Biomedical subjects

P A Pizzo

Publications and source records attributed to P A Pizzo.

At least 19 recordsLinked to original sources
PubMed1992

Changes in T-helper cell function in human immunodeficiency virus-infected children during didanosine therapy as a measure of antiretroviral activity.

Didanosine has shown activity against the human immunodeficiency virus (HIV) in both children and adults. We prospectively assessed T-helper cell (Th) function as determined by in vitro interleukin-2 (IL-2) production in response to a panel of T-cell stimuli in 22 HIV-infected children before and during didanosine therapy and we correlated the incidence of opportunistic and recurrent bacterial infections with changes in p24 antigen and CD4 counts. Didanosine (270, 360, or 540 mg/m2/d) was administered orally for periods ranging from 8 to 40 weeks (mean, 24 weeks). Five of six asymptomatic patients (Centers for Disease Control P-1) compared with 6 of 16 symptomatic (P-2) patients exhibited improved Th function (greater than threefold increase in IL-2 production to at least 2 of the 4 stimuli) during therapy. Of 12 patients without infections during therapy, 9 (75%) showed improvement in Th function, compared with only 2 of 10 patients with infections (P = .03). Notably, the incidence of infections was not correlated with improvements in CD4 count or decreases in p24 antigen. Improvement in Th function during didanosine therapy is correlated with decreased incidence of infections. Assessment of Th function may provide an additional measurement of immunologic response to antiretroviral therapy.

Adolescent↗
PubMed1992

A factor from CD8 cells of human immunodeficiency virus-infected patients suppresses HLA self-restricted T helper cell responses.

Defective in vitro T helper cell (Th) function can occur in asymptomatic human immunodeficiency virus (HIV)-seropositive (HIV+) individuals. A characteristic, early finding is the loss of an in vitro response to recall antigens, such as influenza A virus (FLU), despite an intact Th response to alloantigen (ALLO). To determine whether suppressor cells and/or inhibitory factors could contribute to this HIV-associated Th immunodeficiency, coculture studies were performed using peripheral blood leukocytes (PBLs) from monozygotic twins, one of whom was HIV-infected (HIV+) and one of whom was uninfected (HIV-seronegative, HIV-). In vitro Th function was measured as interleukin 2 production or proliferation to FLU and ALLO. Two pairs of twins were repetitively studied. A single HIV+ individual with multiple samples of cryopreserved PBLs over 6 years (including a HIV- specimen) was also studied. PBLs from the HIV+, but not from the HIV-, individuals demonstrated defective in vitro Th function in response to FLU but not to ALLO. PBLs from HIV+ individuals could induce a similar defect in the Th function of syngeneic or autologous HIV- PBLs. This suppression was generated by CD4-depleted, but not by CD8-depleted, PBLs. A suppressive factor from CD8+ cells of HIV+ donors was generated by 24-hr unstimulated cultures of HIV+ PBLs. This factor inhibited FLU but not ALLO responses of autologous, syngeneic, or allogeneic HIV- PBLs. This suppressive effect could not be explained by HIV infection or replication during the culture period. These results demonstrate that selective abrogation of Th function to recall antigens in HIV+ individuals is associated with an inhibitory factor produced by CD8+ T cells.

CD8 Antigens↗
PubMed1992

NIH conference. Respiratory disease in the immunosuppressed patient.

Pulmonary complications, both infectious and noninfectious, are an important cause of morbidity in patients with various types of immunosuppression. The appropriate response to these clinical problems requires an understanding of pulmonary host defense and of the various types of systemic immunosuppression. Infectious and noninfectious pulmonary complications may vary according to the type of immunosuppression as well as to the degree and duration of immunosuppression. Appropriate clinical management also requires an understanding of the clinical problems commonly seen in specific groups of immunosuppressed patients and an understanding of the sensitivity, specificity, and potential complications associated with the available diagnostic approaches to those patients. Because respiratory disease in these patient groups may progress rapidly to respiratory failure, an expeditious evaluation based on the knowledge of likely causes of respiratory disease and prompt specific or empiric therapy are indicated. Specific sets of algorithms for the evaluation of both focal and diffuse pulmonary disease may facilitate such an evaluation. In addition, an aggressive approach to the prevention of pulmonary disease including immunization, prophylaxis, and immunomodulation (for example, colony stimulating factors) may be warranted in specific subgroups at risk.

Algorithms↗
PubMed1992

Retinal toxicity in human immunodeficiency virus-infected children treated with 2',3'-dideoxyinosine.

To assess the safety and antiretroviral activity of 2',3'-dideoxyinosine, we enrolled 43 children with symptomatic (Centers for Disease Control class P-2) human immunodeficiency virus infection in a Phase I-II study and monitored them prospectively for the development of ocular complications secondary to HIV infection or drug toxicity. Follow-up ranged from 12 to 103 weeks with a median follow-up of 71 weeks. Three of 43 children (7.0%) developed peripheral atrophy of the retinal pigment epithelium during treatment with 2',3'-dideoxyinosine. The two children with the most severe retinal atrophy were enrolled in the study at the highest dosage studied (540 mg/m2/day). In contrast to findings in children, no retinal atrophy in HIV-infected adults treated with 2',3'-dideoxyinosine has been evident to date.

Atrophy↗
PubMed1992

CD4 status and P24 antigenemia. Are they useful predictors of survival in HIV-infected children receiving antiretroviral therapy?

OBJECTIVE: To determine the relationship between CD4 status and the P24 antigen level and survival in children infected with the human immunodeficiency virus. DESIGN: Cohort, case-control. SETTING: Clinical Center at the National Institutes of Health, Bethesda, Md. PARTICIPANTS: One hundred forty-seven children infected with the human immunodeficiency virus enrolled in antiretroviral therapy protocols at the National Cancer Institute were reviewed and the relationships between CD4 counts, P24 antigenemia, and death were analyzed. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: The presence of a very low CD count, less than 21% of the lower limit of normal values for age (equivalent to 0.05 x 10(9)/L in an adult), was associated with a significantly increased risk of death within 2 years. Although the risk of death was highest for children with CD4 counts below this level and who had detectable P24 antigen levels, P24 antigenemia by itself contributed little to the prognostic value of the CD4 count alone. However, it was also notable that a group of children with low CD4 counts also experienced prolonged survival. CONCLUSIONS: The association between low CD4 counts and death suggests that the age-adjusted CD4 count should be used as a marker to guide therapeutic intervention. At the same time, the presence of a very low CD4 count alone should not be considered a reason for therapeutic nihilism.

Age Factors↗
PubMed1992

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.

Brain↗
PubMed1992

Treatment of aggressive cytomegalovirus retinitis with ganciclovir in combination with foscarnet in a child infected with human immunodeficiency virus.

Ganciclovir and foscarnet are both effective for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome, but the benefits of either agent given alone are limited. A child infected with human immunodeficiency virus who had cytomegalovirus retinitis that progressed despite treatment with either agent alone received the combination of ganciclovir and foscarnet. This treatment resulted in a sustained clinical response.

Antiviral Agents↗
PubMed1992

Defining the population of human immunodeficiency virus-infected children at risk for Mycobacterium avium-intracellulare infection.

We reviewed the 22 cases of Mycobacterium avium-intracellulare (MAI) infection that occurred among 196 human immunodeficiency virus-infected children seen at the National Cancer Institute Pediatric Branch from December 1986 through April 1991, and an additional 65 charts from children with cultures negative for MAI. All patients with proven MAI were receiving antiretroviral therapy with zidovudine, dideoxyinosine, or a combination of zidovudine and dideoxycytidine. All patients had disseminated MAI infection, except one adolescent who had only evidence of localized lymphadenitis. All cases of MAI but one were diagnosed before death. The overall incidence of MAI was 11% in our patients but increased to 24% in patients whose absolute CD4 cell counts were < 100 cells/mm3. Symptoms most commonly associated with MAI infection included recurrent fever (86% of patients), weight loss or failure to thrive (64%), neutropenia (55%), night sweats (32%), and abdominal pain (27%). Children infected with MAI had a mean CD4 percentage of 2% (range, 0% to 7%) and a mean absolute CD4 count of 12 cells/mm3 (range, 0 to 48 cells/mm3), significantly lower than in the remainder of the clinic population or the group of children with cultures negative for MAI. Of 20 patients with MAI infection who were tested, 10 had measurable p24 antigen with a mean value 939 pg/ml (range, 77 to 3270 pg/ml) compared with 19 of 59 patients without MAI infection in whom the mean positive value was 413 pg/ml. There was no difference in survival time between those children with documented MAI infection (median survival time, 45.5 weeks) and those with similarly low CD4 counts and cultures negative for MAI (median survival time, 50.4 weeks). Future improvements in therapeutic options may make screening of pediatric human immunodeficiency virus-infected patients with low CD4 counts a reasonable plan.

AIDS-Related Opportunistic Infections↗
PubMed1992

Combination treatment with azidothymidine and granulocyte colony-stimulating factor in children with human immunodeficiency virus infection.

Bone marrow suppression is the major dose-limiting toxic effect of zidovudine (azidothymidine; AZT) in children with human immunodeficiency virus infection. We evaluated the effect of subcutaneously administered granulocyte colony-stimulating factor (G-CSF) in pediatric patients whose absolute neutrophil count was less than 0.8 x 10(9)/L during AZT therapy despite dosage reductions to 120 mg/m2 every 6 hours. Nineteen patients between 6 months and 20 years of age were treated with AZT and G-CSF and monitored for 2 to 12 months. All had previously shown improvement while receiving AZT but had required dosage reduction or discontinuation. By using a sliding dosing schedule of G-CSF, we attempted to maintain the absolute neutrophil count between 1.5 and 5.0 x 10(9)/L. Administration of G-CSF resulted in a significant increase in the median leukocyte count (2.0 x 10(9)/L to 4.14 x 10(9)/L; p = 0.004), and the median absolute neutrophil count (1.02 x 10(9)/L to 2.96 x 10(9)/L; p = 0.0006). G-CSF was well tolerated, but mild thrombocytopenia developed in nine children. Administration of G-CSF and AZT was discontinued in two patients because of continuing neutropenia. With doses of G-CSF ranging from 1 to 20 micrograms/kg per day, 17 of 19 patients were able to tolerate AZT at a dose of 120 to 180 mg/m2 every 6 hours. We conclude that G-CSF therapy enables patients who have had AZT-related neutropenia to receive therapeutic doses of AZT.

Adolescent↗
PubMed1992

Safety and pharmacokinetics of fluconazole in children with neoplastic diseases.

To evaluate the safety, tolerance, and pharmacokinetics of fluconazole in children with neoplastic diseases, we studied fluconazole in 26 children, aged 5 to 15 years, with normal renal function who were receiving treatment for cancer. The patients received fluconazole, 2, 4, or 8 mg/kg per day for 7 days intravenously for a 2-hour period. Patients had no nausea or vomiting related to fluconazole; three patients had an asymptomatic rise in hepatic aminotransferase values after four to six doses (one patient at 2 mg/kg per day and two patients at 8 mg/kg per day), which returned to normal within 2 weeks after discontinuation of the drug. Fluconazole showed linear first-order kinetics over the dosage range tested and during multiple dosing. After the first dose, mean clearance was 22.8 +/- 2.3 ml/min, volume of distribution 0.87 +/- 0.06 L/kg, and terminal elimination half-life 16.8 +/- 1.1 hours. Similarly, after the last dose, clearance was 19.4 +/- 1.3 ml/min, volume of distribution 0.84 +/- 0.04 L/kg, and terminal elimination half-life 18.1 +/- 1.2 hours. Patients receiving their first fluconazole dose of 8 mg/kg achieved peak serum levels of 9.5 +/- 0.4 microgram/ml and trough levels of 2.7 +/- 0.5 microgram/ml 24 hours later, and an area under the serum concentration-time curve from time zero to infinity of 186 +/- 16 micrograms.hr per milliliter. Renal clearance of fluconazole was 65% +/- 5% of total clearance and demonstrated the predominantly renal excretion of this drug. We suggest that the shorter serum half-life and the higher frequency of aminotransferase elevations in comparison with those of adults warrant careful investigation of fluconazole in controlled clinical trials.

Child↗
PubMed1992

Modulation of host defenses by cytokines: evolving adjuncts in prevention and treatment of serious infections in immunocompromised hosts.

Traditional management of infectious complications, especially in immunocompromised hosts, has depended on the prompt initiation of therapy with broad-spectrum antibiotics. During the past several years, however, a number of cytokines (interleukins, hematopoietic growth factors, interferons) have been developed and produced by recombinant DNA technology, and preclinical and clinical studies of cytokines in immunocompromised hosts have begun. The data being generated suggest that certain cytokines can accelerate neutrophil and monocyte/macrophage production, enhance their function, and potentially decrease infectious complications. The role of these agents in both the prevention and treatment of infectious diseases represents an important research challenge and offers new approaches to the prevention and treatment of infection in immunocompromised hosts.

Cytokines↗
PubMed1992

Evaluation of new anti-infective drugs for the treatment of febrile episodes in neutropenic patients. Infectious Diseases Society of America and the Food and Drug Administration.

The use of empirical antimicrobial therapy has significantly reduced the morbidity and mortality associated with untreated infections in febrile neutropenic patients. This guideline describes clinical trials of the safety and efficacy of new antimicrobial drugs in this population of patients. Fever and neutropenia should be precisely defined in each protocol. Patients should be randomized to treatment with a new or active-control drug regimen, stratified on the basis of type of cancer and age, and treated until resolution--as defined in the protocol--is attained. Outcome should be assessed both for cases with a defined microbial etiology and for those without. Final microbiological outcome is important for cases with identified pathogens, but clinical outcome is paramount.

Anti-Infective Agents↗
PubMed1992

Vascular catheter-associated fungemia in patients with cancer: analysis of 155 episodes.

We reviewed all 155 episodes of central venous catheter-associated fungemia among inpatients at the National Cancer Institute during a 10-year period. Candida species accounted for 98% of episodes. Fungemia was documented by culture of blood drawn through catheters in 50% of cases and by culture of both catheter-drawn and peripheral blood in 39%; mortality and the rate of dissemination were similar for these two groups. Four management strategies were used: catheter removal, antifungal therapy (with amphotericin B), both, or neither; indications for the use of both modes of treatment included fever, neutropenia, long-term indwelling catheterization, positive cultures of both catheter-drawn and peripheral blood, isolation of Candida tropicalis, and fungal isolation from two or more blood cultures. Disseminated fungal infection was documented in 82% of cases with these features but also in 35% of the less severe cases treated only with catheter removal. In addition, nine (82%) of 11 cases managed only with antifungal therapy had a negative outcome (either death from disseminated infection or the recurrence of fevers and/or fungemia), a finding suggesting that intravascular catheters should be removed in fungemia. Virtually all cases of catheter-associated fungemia in patients with cancer are clinically significant and require prompt therapy with amphotericin B.

Adolescent↗
PubMed1992

Disseminated infection with Mycobacterium gordonae: report of a case and critical review of the literature.

Mycobacterium gordonae is only rarely a cause of infection despite its ubiquity in the environment. We describe an 11-year-old girl with disseminated infection due to M. gordonae whose course was complicated by renal failure requiring hemodialysis but who recovered after 15 months of chemotherapy. In a literature search we identified 23 additional cases of infection attributed to M. gordonae, with involvement of the lungs (eight), soft tissue (seven), the peritoneal cavity (three), the cornea (one), and with disseminated disease (five patients, including ours). Two patients were infected with human immunodeficiency virus. We assessed the patterns of infection characteristic of each site and the antibiotic sensitivities of the isolates. Adequate documentation of M. gordonae infection (e.g., amount of growth per culture, detection of specific biochemical characteristics, and confirmation of the organism's identity by a reference center) was lacking in many reports. M. gordonae should not automatically be dismissed as a contaminant when isolated from clinical material. Additional studies are required to establish the extent of this organism's pathogenic role.

Acute Kidney Injury↗