Original Article
A Controlled Trial of Interferon Gamma to Prevent Infection in Chronic Granulomatous Disease — The International Chronic Granulomatous Disease Cooperative Study Group*
N Engl J Med 1991; 324:509-516February 21, 1991
- Abstract
- Abstract
Background.
Chronic granulomatous disease is an uncommon inherited disorder of phagocytes in which defective production of the reactive intermediates of oxygen predisposes patients to recurrent and severe pyogenic infections. Evidence from in vitro and in vivo studies indicates that interferon gamma can partially correct the metabolic defect in phagocytes. We assessed the efficacy of interferon gamma in decreasing the frequency of serious infections in patients with this disease.
Methods.
We conducted a randomized, double-blind, placebo-controlled study in 128 patients with chronic granulomatous disease (median age, 15 years). Patients received interferon gamma (50 μg per square meter of body-surface area) or placebo subcutaneously, three times a week for up to a year. The primary end point of the study was the time to the first serious infection, defined as an event requiring hospitalization and parenteral antibiotics. Measures of phagocyte function were also monitored.
Results.
In terms of the time to the first serious infection, there was a clear benefit from interferon as compared with placebo (P = 0.0006). Of the 63 patients assigned to interferon, 14 had serious infections, as compared with 30 of the 65 patients assigned to placebo (P = 0.002). There was also a reduction in the total number of serious infections — 20 with interferon as compared with 56 with placebo (P<0.0001). Interferon was beneficial regardless of age, the use or nonuse of prophylactic antibiotics, and the mode of inheritance (X-linked or autosomal recessive). However, there were no significant changes in the measures of Superoxide production by phagocytes. Interferon therapy was well tolerated, and there was no evidence of serious toxicity.
Conclusions.
For patients with chronic granulomatous disease, interferon gamma therapy is an effective and well-tolerated treatment that reduces the frequency of serious infections. (N Engl J Med 1991; 324:509–16.)
Media in This Article
Figure 1
Cumulative Proportion of Patients in Each Treatment Group Who Were Free of Serious Events (Infections) during the Study.Figure 2
Proportion of Patients in Each Treatment Group Who Were Free of Serious Events, According to Age, Pattern of Disease Inheritance, and Use of Prophylactic Antibiotics.Article Activity
- Article
CHRONIC granulomatous disease is a heterogeneous group of uncommon inherited disorders characterized by recurrent pyogenic infections that usually begin early in life and may lead to death in childhood.1 2 3 Two thirds of the cases involve disease inherited according to an X-linked pattern, and one third follow an autosomal recessive pattern.4 , 5 Although phagocytes from patients with chronic granulomatous disease ingest microorganisms normally, killing is deficient because the capacity of the phagocytes to produce Superoxide and related microbicidal oxygen intermediates is impaired by NADPH oxidase deficiency.6 7 8 9 This oxidase is a multicomponent complex that includes a unique membrane-bound cytochrome b and several cytosolic components. The cytochrome b is a heterodimer consisting of a 91-kd glycosylated heavy chain and a 22-kd light chain, termed "gp91-phox" (phagocyte oxidase) and "p22-phox," respectively.10 , 11 The gene for the heavy chain is the site of mutations responsible for X-linked chronic granulomatous disease.12 , 13 A deficiency of a 47-kd cytosolic protein (p47-phox) required for oxidase activity5 , 14 accounts for most of the autosomal recessive forms14 15 16 17 18 of this disorder. Two rare subgroups of autosomal recessive chronic granulomatous disease are due to defects in the gene for the light chain of the cytochrome b 19 or a defect in the product of a gene encoding for a 67-kd cytosolic protein (p67-phox).5 , 15 , 16 , 20 , 21
The level of activity of NADPH oxidase, which is dormant in resting cells, is affected by exposure to priming substances, including cytokines22 23 24 25 and bacterial lipopolysaccharides.24 These agents do not directly activate the oxidase but serve to enhance its level of activity after stimulation. Experiments in both humans and mice have shown that interferon gamma is a principal macrophage-activating factor. Administering interferon gamma either in vivo or in vitro enhances both the production of reactive oxygen intermediates and the killing of bacterial and protozoal pathogens.26 The use of interferon gamma in clinical trials in patients with lepromatous leprosy and cancer enhanced the capacity of circulating monocytes to secrete hydrogen peroxide.25 , 27 Moreover, interferon gamma has recently been shown to be a potentially important adjunct to conventional therapy for systemic leishmaniasis.28
When interferon gamma was added in vitro to granulocytes and monocytes from patients with various genetic types of chronic granulomatous disease, the defect in Superoxide production was partially corrected in some patients' phagocytes.29 , 30 Partial correction of the functional defect was also observed after treatment of patients with subcutaneous interferon gamma.30 , 31 Since the treatment was well tolerated, a randomized, double-blind, placebo-controlled trial was designed to determine whether interferon gamma could decrease the frequency and severity of serious episodes of infection and improve chronic infectious and inflammatory conditions in patients with all genetic types of chronic granulomatous disease.
Methods
Patients
This trial involved 13 study centers in four countries. Patients who were enrolled had a confirmed diagnosis of chronic granulomatous disease before entry; the diagnosis was based on both abnormal results on neutrophil nitroblue tetrazolium slide testing (after stimulation with phorbol myristate acetate) and neutrophil superoxide production no more than 20 percent of normal. Other criteria for eligibility included preserved renal, hepatic, and hematologic function, a minimal life expectancy of three months, and the signing (by the patients or their parents or guardians) of a form giving informed consent. Patients who had previously received interferon gamma were eligible only if it had not been administered for at least three months, if the nitroblue tetrazolium or superoxide assay indicated a return to pretreatment status, and if no antibody to interferon gamma was detected in the serum. Patients were excluded if they had active infection requiring hospitalization and parenteral antibiotic therapy, severe cardiac disease, or confirmed seizure disorders, had not fully recovered from surgery, were pregnant or lactating, or were not practicing effective contraception while of childbearing age.
Patients were allowed to receive prophylactic antibiotic therapy — i.e., trimethoprim–sulfamethoxazole or dicloxacillin — according to a predetermined regimen that varied according to their age and history of drug allergy. Patients receiving corticosteroids were eligible only if they were both receiving 10 mg or less of prednisone daily and had been receiving the same dose for at least one month before entering the study. The use of other forms of immunotherapy, experimental drugs (including itraconazole, then experimental), and antiinflammatory compounds was not permitted during the study period.
Study Medication
Recombinant human interferon gamma (Genentech, South San Francisco; specific activity, approximately 3×107 U per milligram of protein) was supplied as a sterile solution ready for injection. Each vial contained either 0.2 mg of interferon gamma at a concentration of 0.2 mg per milliliter or placebo (interferon gamma diluent) and was labeled according to a centrally prepared randomization list.
Study Design
Patients were randomly assigned to treatment according to a dynamic, adaptive randomization scheme32 , 33 stratified on the basis of the pattern of inheritance of the disease (X-linked or autosomal recessive), the use or nonuse of prophylactic antibiotics, the study-center institution (United States — a center of the National Institutes of Health or other centers; Europe — Amsterdam center or other centers), and the use or nonuse of corticosteroids. All patients, investigators, and trial coordinators were blinded to treatment assignment. The patients received interferon gamma or placebo by subcutaneous injection three times weekly (e.g., on Monday, Wednesday, and Friday) for up to 12 months unless unacceptable toxicity was observed. If the body-surface area of a patient was at least 0.5 m2, the dose was administered on the basis of body-surface area, as 50 μg per square meter; if the body-surface area was less than 0.5 m2, the dose was administered on the basis of body weight, as 1.5 μg per kilogram. Patients were carefully monitored on a periodic basis for clinical or laboratory evidence of toxicity related to interferon gamma. Toxicity was graded according to criteria specified in the protocol.
Monitoring for Efficacy
Serious Infections
The primary end point of this investigation was the time to serious infection, defined as a clinical event requiring both hospitalization and the administration of parenteral antibiotics. The time to the first serious infection was calculated as the number of days elapsed between the date of random assignment to treatment and the date of diagnosis of the infection. Patients were also followed up for the number and relative rate of serious infections. The assigned treatment was continued during periods of serious or minor infection. Patients discontinuing treatment at any time during the study period continued to be monitored to document the occurrence of the first serious infection (primary end point) and subsequent recurrent serious infections.
Chronic Clinical Conditions Related to Chronic Granulomatous Disease
Quantitative estimates of the severity of all clinical conditions related to chronic granulomatous disease were obtained within seven days before the initiation of treatment and at three-month intervals during the study. Two scoring systems were used: a visual-analogue system for scoring clinical severity, in which an absolute rating of the severity of each condition was recorded as a tick mark on a linear scale ranging from "absent" to "most severe," and a system for scoring clinical change ("change from first identification"), in which a seven-point scale ranging from –3 (severe worsening of >50 percent) to +3 (complete resolution) was used to assess change in each condition relative to its first occurrence. All evaluations of each patient were performed by the same physician.
Phagocyte-Function Assays
Neutrophil Nitroblue Tetrazolium Test
The neutrophil nitroblue tetrazolium test34 , 35 was performed on fresh whole blood or isolated neutrophils. Equal volumes of cells were incubated in a solution of neutrophil nitroblue tetrazolium with 1 μg of phorbol myristate acetate per milliliter (stimulated incubation) and without it (unstimulated incubation). After incubation, the cells were fixed and counterstained with 1 percent safranin. The percentage of positive cells was determined microscopically. When the percentage of normal neutrophils is more than 95 percent, the neutrophil nitroblue tetrazolium is reduced.
Phagocyte Superoxide-Production Assay
The effect of interferon gamma on phagocyte respiratory-burst activity was determined by measuring the rate at which superoxide was generated by neutrophils in suspension (and, when available, monocytes) before and after stimulation with phorbol myristate acetate (660 ng per milliliter); this assay was performed before treatment and on days 4, 90, 180, 270, and 360. Superoxide was measured with a discontinuous, end-point assay (after 10 and 60 minutes) in which ferricytochrome c was used as the indicator of the presence or absence of superoxide dismutase.36 Determinations were averaged before analysis. The two treatment groups were compared at each study visit with respect to differences in the rate of superoxide production (expressed as the number of nanomoles produced per 10 minutes).
Phagocytic Killing of Staphylococci
The effect of interferon gamma on bacterial killing of Staphylococcus aureus strain 502A34 was measured for each assay time point (one hour and two hours) and cell type (neutrophils and, when available, monocytes) before treatment and on days 4, 90, 180, 270, and 360. The percentage of bacterial killing in patients and normal controls was based on colony counts and bacteria levels in cell-free growth-control preparations. The two treatment groups were compared at each study visit for bacterial killing at each time point and for each cell type.
Statistical Analysis
The time to serious infection was the primary end point of this investigation. The trial was planned to have a minimal enrollment of 100 eligible patients. A patient receiving placebo and prophylactic antibiotics was expected to have at least one serious infection every two years. This ensured that a two-sided log-rank test with a level of significance of 0.05 would have a power of 0.85 to detect a fourfold reduction in the rate of serious infections (from one infection per two years to one per eight years) and a power of more than 0.75 to detect a threefold reduction.
The statistical methods employed included the Cochran—MantelHaenszel test, the Pearson chi-square test, analysis of variance, and the t-test.37 , 38 The distribution of times to serious infection was compared between the groups by means of the log-rank test and the Cox proportional-hazards regression model.39 The Cox proportional-hazards model was also used to determine the relative risk (hazard ratio) of serious infection in the treatment groups and the 95 percent confidence interval for the hazard ratio, and to perform all multivariate analyses. The Andersen—Gill generalization of the Cox regression model for the time to the first serious infection was used in the analysis of data on recurrent serious infection.40 , 41 Curves showing the cumulative proportion of patients free of serious infection in each group were generated according to the Kaplan–Meier method.42 Statistical analyses were computed with the procedures of SAS and BMDP (P1L and P2L).43 , 44 All P values reported for this trial are two-sided.
The decision to terminate the trial early or to continue it was made during a planned interim analysis performed by an independent monitoring committee that had sole access to blinded data on efficacy. The committee was guided by the two-stage group sequential boundary of O'Brien and Fleming.45 This analysis, based on an average duration of study treatment of 6.4 months and 68 cumulative patient-years, resulted in early termination of the study after interferon gamma therapy was demonstrated to have significant benefit with respect to the time to serious infection, as compared with placebo (20 patients in the placebo group vs. 7 in the interferon group, P = 0.0036).
Results
Characteristics of the Study Population
During a seven-month period a total of 135 patients were randomly assigned to receive either interferon gamma or placebo. Seven patients did not meet the eligibility criteria of the protocol, leaving 128 eligible patients for inclusion in the final analysis. Of the seven ineligible patients, two were using prohibited concomitant medication, two had serious active infections and no signed form giving informed consent, one had a history of seizure disorder and no signed form giving consent, and two declined to participate. As shown in Table 1Table 1
Characteristics of Patients with Chronic Granulomatous Disease, According to Treatment Group.*, the two treatment groups were comparable at admission in age, sex, pattern of inheritance of chronic granulomatous disease, and use of prophylactic antibiotics and corticosteroids.Results of the Final Analysis
The final analysis was conducted with data collected on each patient through the end of the study, from the time of randomization until the date of the final blinded visit, including an additional 2.5 months of follow-up per patient beyond the date of the interim analysis. The average duration of treatment was 8.9 months, representing 95 patient-years. The median age of the patients was 15 years, and 37 patients were less than 9 years of age. One hundred eleven of the 128 eligible patients received the study treatment throughout the entire study period. There were no deaths.
Serious Infections
Thirty (46 percent) of 65 patients in the placebo group and 14 (22 percent) of the 63 in the interferon gamma group had at least one serious infection (P = 0.0006). When the time to the first serious infection in each group was plotted as a Kaplan–Meier curve (Fig. 1Figure 1
Cumulative Proportion of Patients in Each Treatment Group Who Were Free of Serious Events (Infections) during the Study.), a mean (±SE) of 77±0.06 percent of patients in the interferon group were free of serious infection 12 months after randomization, as compared with only 30±0.11 percent in the placebo group (P = 0.0006, by two-sided log-rank test). When these values were compared with those after six months (89±0.04 percent vs. 72±0.06 percent, respectively), the beneficial effect of interferon was clearly maintained with its continued administration during the first year. When the Cox regression model was used, with treatment as a covariate, the relative risk of a serious infection with interferon was only one third the risk with placebo, resulting in a 67 percent reduction in the relative risk of serious infection during interferon treatment (95 percent confidence interval for the relative risk, 0.17 to 0.64; estimated log relative risk [±SE], –1.094±0.34).Recurrent Serious Infections
Of the 30 patients assigned to placebo who had at least one serious event (infection), 5 had two events, 4 others had three, 1 had four, 1 had five, and 1 had seven. Of the 14 patients assigned to interferon gamma who had at least one serious event, 4 had a second event and 1 had three. Comparison of the total numbers and rates of serious infections observed to the end of study showed a significant difference between the groups (56 infections in the placebo group vs. 20 in the interferon group; P<0.0001 by partial-likelihood ratio test derived by fitting an Andersen—Gill regression model). This additional information on recurrent events reduced the variability in the estimate of treatment effect (relative risk, 0.33), reducing the 95 percent confidence interval (0.20 to 0.56) and thereby strengthening the evidence of a beneficial effect of interferon gamma therapy.
Analysis of the nature of serious events revealed that interferon gamma appeared to be most effective in reducing adenitis, abscesses, cellulitis, and pulmonary infections (Table 2Table 2
Clinical Events Requiring Hospitalization and Intravenous Antibiotics.). It was particularly noteworthy that only one patient receiving interferon had an episode of aspergillus pneumonia, as compared with four patients receiving placebo. In addition, patients receiving placebo required three times as many days of hospitalization for the treatment of clinical events as did patients receiving interferon (1493 vs. 497 days, respectively); the average stay was 32 days in the interferon group and 48 days in the placebo group (P = 0.02). Moreover, 13 patients in the placebo group were hospitalized for more than 28 days, as compared with 6 in the interferon group.Subset Analyses
Kaplan–Meier curves were constructed for each category of the following five prognostic or potential confounding factors: pattern of inheritance (X-linked or autosomal recessive), use of prophylactic antibiotics (yes or no), institution (United States, National Institutes of Health; United States, other study center; Europe, Amsterdam; or Europe, other study center), sex, and age (younger, <10 years; or older, ≥ 10 years). The proportions of patients free of serious infection among those with X-linked disease and among those with autosomal recessive disease were similar, as were the proportions among male patients and female patients; however, patients less than 10 years of age and patients not taking prophylactic antibiotics had a slightly greater frequency of serious infections. The group of patients treated at European centers other than Amsterdam appeared to have a slightly greater proportion free of serious infection.
Analyses of the primary end point — the time to serious infection — were conducted to determine whether any of the prognostic factors or potential confounding variables had a significant interaction with treatment. Table 3Table 3
Patients Free of Serious Infection 12 Months after Randomization, after Adjustment for Stratification Factors. shows the estimated percentage of patients free of serious infection in each treatment group after 12 months, in relation to each of the five factors. Figure 2Figure 2Proportion of Patients in Each Treatment Group Who Were Free of Serious Events, According to Age, Pattern of Disease Inheritance, and Use of Prophylactic Antibiotics. shows the Kaplan–Meier curves for analyses according to the pattern of disease inheritance, use of prophylactic antibiotics, and age. In all cases interferon gamma had a benefit as compared with placebo. For example, 79 percent of the patients with X-linked disease and 71 percent of those with autosomal recessive disease in the interferon group were free of serious infection after 12 months, as compared with 33 percent of those with X-linked disease and 39 percent of those with autosomal recessive disease in the placebo group. It is notable that 78 percent of the patients receiving interferon gamma in conjunction with prophylactic antibiotics were free of serious infection after 12 months, as compared with 33 percent of the patients receiving placebo and antibiotics. The greatest effect of treatment with interferon gamma was observed among patients less than 10 years of age; 81 percent of those receiving interferon were free of serious infection after 12 months, as compared with 20 percent of those receiving placebo. The estimate of the percentage reduction in the relative risk of serious infection with interferon as compared with placebo was consistently around 67 percent.Among the patients with X-linked disease, serious adverse events occurred in 19 receiving placebo and 9 receiving interferon gamma; among those with autosomal recessive disease, such events occurred in 11 receiving placebo and 5 receiving interferon. The relative risk of serious infection was 3.4 times greater among patients with X-linked disease who received placebo than among those who received interferon, and 2.3 times greater among patients with autosomal recessive disease. Even though the European centers had a lower overall rate of serious adverse events —probably because they had a shorter follow-up period and older cohorts — there was evidence of benefit from treatment with interferon gamma in both European and American institutions. The relative risk of serious infection was 3.5 times greater with placebo than with interferon in U.S. patients and 2.1 times greater in European patients.
The most striking finding regarding prognostic factors was the beneficial effect of interferon gamma in younger patients. Among patients less than 10 years old there were 15 serious infections with placebo and 6 with interferon, whereas among older patients there were 15 serious infections with placebo and 8 with interferon. Analysis of the time to a first serious infection revealed that the relative risk of serious infection was 4.8 times greater with placebo than with interferon among the younger patients and 2.1 times greater among the older patients.
Chronic Conditions Related to Chronic Granulomatous Disease
The effect of interferon gamma on the relief and prevention of chronic conditions related to chronic granulomatous disease was assessed at each patient visit. These conditions included granulomatous obstruction of the gastrointestinal and genitourinary tracts, fistulas, abscesses, lymphadenitis, and dermatitis. This assessment failed to reveal any statistically significant benefit or deleterious effects of interferon on these conditions, as compared with placebo.
Phagocyte Function
No statistically significant differences were observed between the interferon and placebo groups in either superoxide production or bacterial killing at any of the study time points at any of the centers, as indicated by neutrophil assays performed in all patients and monocyte assays performed in less than 25 percent of the patients. Analysis of the pooled results from all centers gave results similar to those for individual centers. Cytochrome b levels were not routinely measured at all centers because of the technical difficulty and sensitivity of the assay. Where they were measured, however, no effect of interferon gamma on cytochrome b levels was observed (measured in <10 percent of all enrolled patients).
Adverse and Intercurrent Events
No serious or life-threatening toxic effects could be directly attributed to the administration of interferon gamma. The most common clinical reactions observed were fever, chills, headache, and erythema at the injection site (Table 4Table 4
Adverse Reactions during Study.). The majority of reactions were mild, and concomitant administration of acetaminophen appeared to ameliorate most reactions. When interferon gamma was administered at bedtime, there were fewer reactions. Comparison of the incidence of adverse events according to age revealed a greater incidence of reactions in older patients. Constitutional symptoms occurred twice as frequently in patients 10 years old or older as in those less than 10 years old. In children 5 years old or younger, the incidence of adverse reactions was lower than in all the other patients. No adverse effects were observed on growth as determined by weight and height; no obvious effects on development were observed. Four patients were withdrawn from therapy because of toxicity related to interferon: one patient for skin rash, two for constitutional symptoms, and one for worsening granulomatous colitis. No effect of interferon on hematologic or biochemical indexes was observed. Elevation of hepatic enzyme levels was noted in 23 percent of patients receiving placebo and 16 percent of those receiving interferon (all elevations were less than three times base-line values). In addition, interferon gamma had no effects on the levels of rheumatoid factor or antinuclear antibodies, the sedimentation rate, thyroid function, or sex hormone levels. In 54 patients treated with interferon for whom paired blood specimens were available, antibodies against interferon gamma were not detected.Discussion
In this double-blind, placebo-controlled study, subcutaneous injections of recombinant interferon gamma administered three times weekly reduced the frequency of serious infections in patients with chronic granulomatous disease. Interferon was beneficial regardless of the pattern of inheritance of disease, age, or use or nonuse of prophylactic antibiotics. Patients receiving interferon had a reduction in the frequency and total length of hospitalizations. Children less than 10 years of age benefited most from treatment and had fewer side effects. Treatment was not accompanied by toxic effects other than fever, mild headache, and myalgia, which were treated with acetaminophen. No antibodies to interferon gamma were detected.
Since chronic granulomatous disease is often diagnosed during the first few years of life, it is noteworthy that the treatment was well tolerated in patients of this age and was not associated with disturbances in growth and development as determined after 12 months of follow-up. It is especially encouraging that the ability of interferon gamma to reduce infection was most dramatic in children less than 10 years old.
Interferon gamma therapy was effective in all genetic types of chronic granulomatous disease. The precise molecular mechanisms by which it improves host defense in this disorder remain unknown. In the present study, there appeared to be no correlation between the clinical benefit of interferon and the improvement in phagocyte function, in contrast to the results of previous studies.29 30 31 In those studies, neutrophils and monocytes from patients with X-linked disease showed augmented Superoxide production and cytochrome b gene expression after interferon gamma treatment in vitro or in vivo. Several patients with autosomal recessive chronic granulomatous disease who lacked either the p47 or the p67 cytosol oxidase component also had a slight improvement in superoxide production. The most likely explanation for this apparent discrepancy is that although the majority of patients with chronic granulomatous disease do not have improvement in respiratory-burst function, there are rare patients who have mutations that permit a phagocyte response to interferon gamma (e.g., generegulatory mutations). The clinical response of such patients may be due in part to the effect on the respiratory burst. In the majority of patients, however, interferon gamma may confer benefit by augmenting oxygen-independent antimicrobial pathways of phagocytes, which were not determined in this study. Another explanation is that the interferon improved the function of other components of the immune system (e.g., T or B cells). Yet another is that any interferon gamma—induced changes in superoxide production were below the level of detection of the assay for extracellular superoxide or that hydrogen peroxide (rather than superoxide) was preferentially generated by the slight enhancement of oxidase. Further study will be required to determine the effects of interferon gamma on oxygen-dependent and oxygen-independent microbicidal pathways. Molecular characterization of specific defects in a large number of patients within each genetic subgroup, and correlation of the defect with functional response to treatment, should also help define the mechanisms by which interferon gamma augments the host response.
Interferon gamma treatment was accompanied by minimal side effects. Chills, myalgias, and erythema were observed nearly exclusively in the interferon group. Fever, however, occurred in a third of the patients receiving placebo, as compared with half of those receiving interferon. Constitutional side effects were reduced by bedtime administration of interferon gamma with acetaminophen. Although this study establishes an effective dose, dose interval, and route of administration, further studies are planned to evaluate the effectiveness of giving subcutaneous injections weekly as compared with three times weekly.
This study shows that interferon gamma is an effective and safe therapy for patients with chronic granulomatous disease, since the drug substantially reduced the frequency of serious infections. The results strongly support the recommendation that interferon gamma be given to these patients as prophylaxis against infections, either alone or (preferably) in conjunction with prophylactic antibiotics. The potentially effective use of interferon gamma for other infectious diseases, such as leprosy27 and leishmaniasis, 28 together with the realization that mechanisms other than the augmentation of superoxide production probably contribute to the mechanism of action of this agent, suggests that this cytokine may have general applications as an adjunct to conventional antimicrobial agents in the treatment of many types of infectious diseases.
Address reprint requests to Dr. R. Alan B. Ezekowitz at the Department of Pediatrics, Children's Hospital, Enders Bldg. — 7th Fl., 300 Longwood Ave., Boston, MA 02115.
Supported in part by the National Institutes of Health and Genentech, Inc.
*The principal investigators of the study were J.I. Gatlin, H.L. Malech, R.S. Weening, J.T. Curnutte, P.G. Quie, H.S. Jaffe, and R.A.B. Ezekowitz. Fora list of the authors, see the Appendix.
We are indebted to B. Babior, M.D., Ph.D. (Scripps Clinic and Research Foundation, La Jolla, Calif.), R.B. Johnston, M.D. (Children's Hospital of Philadelphia), and S. Klebanoff, M.D. (University of Washington, Seattle), for their participation on the Independent Data Safety and Monitoring Committee; to D.W. Alling, M.D., and S.M. Banks, Ph.D. (National Institutes of Health, Bethesda, Md.), and S.A. Sherwin, M.D. (Genentech, S. San Francisco), for advice on study design and statistical analyses; and to E. De Carlo (National Institutes of Health), J. van Pelt and R. van Zweten (Academic Medical Center and Central Laboratory of the Netherlands Red Cross, Amsterdam), the staff of the Scripps Clinic General Clinical Research Center and S. Burke (La Jolla), I. Tanner and C. Erny (Kinderspital, Zurich), C. Brown and M. Burton (C.S. Mott Children's Hospital, University of Michigan, Ann Arbor), L.C. Hiebert and M. Dombrowski (Baylor College of Medicine, Texas Children's Hospital, Houston), L. Beyer (Children's Hospital of Los Angeles), A. Hansen (Hvidovre Hospital, Copenhagen), B.R. Michael (University of Washington), S. Martin and M. Reiter (Mount Sinai Medical Center, New York), G.J. Leitz, M.D. (Boehringer Ingelheim, Ingelheim, Germany), and P. Tufte, S. Hirabayashi, and J. Diehl (Genentech).
Appendix
The following members of the International Chronic Granulomatous Disease Cooperative Study Group are the authors of this report: J.I. Gallin, M.D., H.L. Malech, M.D., and D.A. Melnick, M.D., National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.; R.S. Weening, M.D., Ph.D., D. Roos, Ph.D., and H. Wendt, M.D., Emma Children's Hospital, Academic Medical Center, and Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam; R.C. Woodman, M.D., and J.T. Curnutte, M.D., Ph.D., Scripps Clinic and Research Foundation, La Jolla, Calif.; R.A. Seger, M.D., T. Muhlebach, Ph.D., and J.P. Bourquin, M.D., Kinderspital, Zurich; R.A. Axtell, M.D., L.A. Boxer, M.D., and C.L. Pierson, Ph.D., C.S. Mott Children's Hospital, University of Michigan, Ann Arbor; D.C. Anderson, M.D., W.T. Shearer, M.D., Ph.D., and H.M. Rosenblatt, M.D., Baylor College of Medicine, Texas Children's Hospital, Houston; J.C. Torkildson, M.D., R.L. Baehner, M.D., and T.D. Coates, M.D., Children's Hospital of Los Angeles; K. Belani, M.D., and P.G. Quie, M.D., University of Minnesota Medical School, Minneapolis; N.H. Valerius, M.D., C. Koch, M.D., and F.K. Pedersen, M.D., Hvidovre Hospital, Copenhagen; H.R. Hill, M.D., and A. Shigeoka, M.D., University of Utah, School of Medicine, Salt Lake City; S.H. Fischer, M.D., H. Rosen, M.D., H.D. Ochs, M.D., and T.R. Fleming, Ph.D., University of Washington, Seattle; C. Cunningham Rundles, M.D., Ph.D., A. Hyatt, M.D., and H. Evrard, M.D., Mount Sinai Medical Center, New York; C. Nathan, M.D., and C. Farber, M.D., Cornell University and New York Hospital, New York; R.A.B. Ezekowitz, M.B.Ch.B., D.Phil., Harvard Medical School and Children's Hospital, Boston; and A.E. Izu, M.S., S.M. Kramer, Dr.P.H., and H.S. Jaffe, M.D., Department of Clinical Research, Genentech, Inc., South San Francisco.
- References
References
1
Forrest
Web of Science | Medline2
Tauber
Web of Science | Medline3
Curnutte
Web of Science | Medline4
Mills EL, Quie PG. Inheritance of chronic granulomatous disease. In: Gallin JI, Fauci AS, eds. Chronic granulomatous disease. Vol. 3 of Advances in host defense mechanisms. New York: Raven Press, 1983:25–53.
5
Clark
Full Text | Web of Science | Medline6
Baehner
CrossRef | Web of Science | Medline7
Curnutte
Full Text | Web of Science | Medline8
Babior
Web of Science | Medline9
Curnutte
Full Text | Web of Science | Medline10
Parkos
CrossRef | Web of Science | Medline11
Segal
CrossRef | Web of Science | Medline12
Royer-Pokora
CrossRef | Web of Science | Medline13
Dinauer
CrossRef | Web of Science | Medline14
Curnutte
CrossRef | Web of Science | Medline15
Volpp
CrossRef | Web of Science | Medline16
Nunoi
CrossRef | Web of Science | Medline17
Lomax
CrossRef | Web of Science | Medline18
Volpp
CrossRef | Web of Science | Medline19
Dinauer
CrossRef | Web of Science | Medline20
Curnutte
CrossRef | Web of Science | Medline21
Leto
CrossRef | Web of Science | Medline22
Nathan
Medline23
Berton
CrossRef | Web of Science | Medline24
Guthrie
CrossRef | Web of Science | Medline25
Nathan
CrossRef | Web of Science | Medline26
Murray
Web of Science | Medline27
Nathan
Full Text | Web of Science | Medline28
Badaro
Full Text | Web of Science | Medline29
Ezekowitz
CrossRef | Web of Science | Medline30
Sechler
CrossRef | Web of Science | Medline31
Ezekowitz
Full Text | Web of Science | Medline32
Efron
CrossRef | Web of Science33
Hannigan JF, Brown BW. Adaptive randomization biased coin-design: experience in a cooperative group clinical trial. Technical report no. 74. Palo Alto, Calif.: Division of Biostatistics, Stanford University, 1982.
34
Babior BM, Cohen HJ. Measurement of neutrophil function: phagocytosis, degranulation, the respiratory burst, and bacterial killing. In: Cline MJ, ed. Leukocyte function. New York: Churchill Livingstone, 1981:1–38.
35
Ezekowitz
CrossRef | Web of Science | Medline36
Curnutte
CrossRef | Web of Science | Medline37
Fleiss JL. The design and analysis of clinical experiments. New York: John Wiley, 1986.
38
Winer BJ. Statistical principles in experimental design. 2nd ed. New York: McGraw-Hill, 1971.
39
Cox 40
Andersen
CrossRef | Web of Science41
Fleming TR, Harrington DP. Counting processes and survival analysis. New York: John Wiley (in press).
42
Kaplan
CrossRef | Web of Science43
Dixon WJ, ed. BMDP biomedical computer programs (P-series). Berkeley: University of California Press, 1981.
44
SAS Institute Inc. SAS user's guide: statistics, version 5 edition. Cary, N.C.: SAS Institute, 1985.
45
O'Brien
CrossRef | Web of Science | Medline
- Citing Articles (198)
Citing Articles
1
Fariba Naderi beni, Fatemeh Fattahi, Abbas Mirshafiey, Mohammad Ansari, Monireh Mohsenzadegan, Masoud Movahedi, Zahra Pourpak, Mostafa Moin. (2012) Increased production of nitric oxide by neutrophils from patients with chronic granulomatous disease on interferon-gamma treatment. International Immunopharmacology
CrossRef2
Charalampos Antachopoulos, Aspasia Katragkou, Emmanuel Roilides. (2012) Immunotherapy against invasive mold infections. Immunotherapy 4:1, 107-120
CrossRef3
S. Blumental, R. Mouy, N. Mahlaoui, M.-E. Bougnoux, M. Debre, J. Beaute, O. Lortholary, S. Blanche, A. Fischer. (2011) Invasive Mold Infections in Chronic Granulomatous Disease: A 25-Year Retrospective Survey. Clinical Infectious Diseases 53:12, e159-e169
CrossRef4
Scott J. Bergman, McKenzie C. Ferguson, Cathy Santanello. (2011) Interferons as Therapeutic Agents for Infectious Diseases. Infectious Disease Clinics of North America 25:4, 819-834
CrossRef5
B. Piraino, U. Vollmer-Conna, A.R. Lloyd. (2011) Genetic associations of fatigue and other symptom domains of the acute sickness response to infection. Brain, Behavior, and Immunity
CrossRef6
John Dotis, Emmanuel Roilides. (2011) Osteomyelitis due to Aspergillus species in chronic granulomatous disease: an update of the literature. Mycoses 54:6, e686-e696
CrossRef7
Caridad A. Martinez, Sweta Shah, William T. Shearer, Howard M. Rosenblatt, Mary E. Paul, Javier Chinen, Kathryn S. Leung, Alana Kennedy-Nasser, Malcolm K. Brenner, Helen E. Heslop, Hao Liu, Meng-Fen Wu, Imelda C. Hanson, Robert A. Krance. (2011) Excellent survival after sibling or unrelated donor stem cell transplantation for chronic granulomatous disease. Journal of Allergy and Clinical Immunology
CrossRef8
Harry R. Hill. (2011) Hyperinflammatory Pulmonary Disease in Chronic Granulomatous Disease. The Pediatric Infectious Disease Journal 30:9, 808-810
CrossRef9
Hsien-Mei Chang, Hsin-Hui Yu, Yao-Hsu Yang, Wen-I Lee, Jyh-Hong Lee, Li-Chieh Wang, Yu-Tsan Lin, Bor-Luen Chiang. (2011) Successful Treatment of Aspergillus flavus Spondylodiscitis With Epidural Abscess in a Patient With Chronic Granulomatous Disease. The Pediatric Infectious Disease Journal1
CrossRef10
Julie V. Schaffer, Amy S. Paller. 2011. Immunodeficiency Syndromes. , 177.1-177.34.
CrossRef11
Elizabeth M. Kang, Betty E. Marciano, SukSee DeRavin, Kol A. Zarember, Steven M. Holland, Harry L. Malech. (2011) Chronic granulomatous disease: Overview and hematopoietic stem cell transplantation. Journal of Allergy and Clinical Immunology 127:6, 1319-1326
CrossRef12
K.F. Heim, T.A. Fleisher, D.F. Stroncek, S.M. Holland, J.I. Gallin, H.L. Malech, S.F. Leitman. (2011) The relationship between alloimmunization and posttransfusion granulocyte survival: experience in a chronic granulomatous disease cohort. Transfusion 51:6, 1154-1162
CrossRef13
V. Wahn, F. Zepp, M. Borte, W. Friedrich. (2011) Primäre Immundefekte. Monatsschrift Kinderheilkunde 159:5, 443-450
CrossRef14
M. Teresa de la Morena, Richard A. Gatti. (2011) A History of Bone Marrow Transplantation. Hematology/Oncology Clinics of North America 25:1, 1-15
CrossRef15
Cary Qualia, Athos Bousvaros. 2011. Gastrointestinal Manifestations of Primary Immunodeficiency. , 435-446.
CrossRef16
Brahm H. Segal, Paul Veys, Harry Malech, Morton J. Cowan. (2011) Chronic Granulomatous Disease: Lessons from a Rare Disorder. Biology of Blood and Marrow Transplantation 17:1, S123-S131
CrossRef17
M. Teresa de la Morena. 2011. Congenital Immunodeficiencies. , 1292-1301.
CrossRef18
Kuhns, Douglas B., Alvord, W. Gregory, Heller, Theo, Feld, Jordan J., Pike, Kristen M., Marciano, Beatriz E., Uzel, Gulbu, DeRavin, Suk See, Priel, Debra A. Long, Soule, Benjamin P., Zarember, Kol A., Malech, Harry L., Holland, Steven M., Gallin, John I., . (2010) Residual NADPH Oxidase and Survival in Chronic Granulomatous Disease. New England Journal of Medicine 363:27, 2600-2610
Full Text19
Pérsio Roxo, Ullissis Pádua de Menezes, Antônio Condino-Neto, Virgínia Paes Leme Ferriani, Osvaldo M. Takayanagui. (2010) Unusual Presentation of Brain Aspergillosis in Chronic Granulomatous Disease. Pediatric Neurology 43:6, 442-444
CrossRef20
Kyle Strimbu, Jorge A Tavel. (2010) What are biomarkers?. Current Opinion in HIV and AIDS 5:6, 463-466
CrossRef21
S. S. De Ravin, K. A. Zarember, D. Long-Priel, K. C. Chan, S. D. Fox, J. I. Gallin, D. B. Kuhns, H. L. Malech. (2010) Tryptophan/kynurenine metabolism in human leukocytes is independent of superoxide and is fully maintained in chronic granulomatous disease. Blood 116:10, 1755-1760
CrossRef22
C. Antachopoulos. (2010) Invasive fungal infections in congenital immunodeficiencies. Clinical Microbiology and Infection 16:9, 1335-1342
CrossRef23
Yu-Hao Chang, Hsin-Hui Yu, Yu-Lung Lau, Koon-Wing Chan, Bor-Luen Chiang. (2010) A new autosomal recessive, heterozygous pair of mutations of CYBA in a patient with chronic granulomatous disease. Annals of Allergy, Asthma & Immunology 105:2, 183-185
CrossRef24
Jaffar A. Al-Tawfiq, Hail M. Al-Abdely. (2010) Vertebral osteomyelitis due to Aspergillus fumigatus in a patient with chronic granulomatous disease successfully treated with antifungal agents and interferon-gamma. Medical Mycology 48:3, 537-541
CrossRef25
S. M. Breathnach. 2010. Drug Reactions. , 1-177.
CrossRef26
Sergio D Rosenzweig, Harry L Malech. 2010. Neutrophil Functional Disorders. .
CrossRef27
Sumita Roy-Ghanta, Jordan S. Orange. (2010) Use of Cytokine Therapy in Primary Immunodeficiency. Clinical Reviews in Allergy & Immunology 38:1, 39-53
CrossRef28
Turkan Patiroglu, Ekrem Unal, Ali Yikilmaz, M. Yavuz Koker, Mustafa K. Ozturk. (2010) Atypical presentation of chronic granulomatous disease in an adolescent boy with frontal lobe located Aspergillus abscess mimicking intracranial tumor. Child's Nervous System 26:2, 149-154
CrossRef29
M. Teresa de la Morena, Richard A. Gatti. (2010) A History of Bone Marrow Transplantation. Immunology and Allergy Clinics of North America 30:1, 1-15
CrossRef30
Steven M. Holland. (2010) Chronic Granulomatous Disease. Clinical Reviews in Allergy & Immunology 38:1, 3-10
CrossRef31
S. M. Breathnach. 2010. , 1.
CrossRef32
Mizuka Miki, Atsushi Ono, Ayumi Awaya, Shinichiro Miyagawa, Rie Onodera, Emi Kurita, Asako Hiraoka, Fumio Hidaka, Tomoyuki Mizukami, Hiroyuki Nunoi, Masao Kobayashi. (2009) Successful bone marrow transplantation in chronic granulomatous disease. Pediatrics International 51:6, 838-841
CrossRef33
Jay Yeh, Casey Culbertson, Ann M. Petru. (2009) Purulent Pericardial Effusion in a 14-Year-Old Girl. The Pediatric Infectious Disease Journal 28:12, 1140, 1147-1148
CrossRef34
Orest Hurko. (2009) The Uses of Biomarkers in Drug Development. Annals of the New York Academy of Sciences 1180:1, 1-10
CrossRef35
Tetsuya Horino, Tetsuya Matsumoto, Hiroki Ishikawa, Soichiro Kimura, Masashi Uramatsu, Masaaki Tanabe, Kazuhiro Tateda, Shuichi Miyazaki, Yukihiko Aramaki, Yoichiro Iwakura, Masaki Yoshida, Shoichi Onodera, Keizo Yamaguchi. (2009) Interleukin-1 deficiency in combination with macrophage depletion increases susceptibility to Pseudomonas aeruginosa bacteremia. Microbiology and Immunology 53:9, 502-511
CrossRef36
Talmadge E King, Carlo Albera, Williamson Z Bradford, Ulrich Costabel, Phil Hormel, Lisa Lancaster, Paul W Noble, Steven A Sahn, Javier Szwarcberg, Michiel Thomeer, Dominique Valeyre, Roland M du Bois. (2009) Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial. The Lancet 374:9685, 222-228
CrossRef37
K. Hara, T. Kajiume, T. Kondo, Y. Sera, H. Kawaguchi, M. Kobayashi. (2009) Respiratory complications after haematopoietic stem cell transplantation in a patient with chronic granulomatous disease. Transfusion Medicine 19:2, 105-108
CrossRef38
Elena Soncini, Mary A. Slatter, Laura B. K. R. Jones, Stephen Hughes, Stephen Hodges, Terence J. Flood, Dawn Barge, Gavin P. Spickett, Graham H. Jackson, Matthew P. Collin, Mario Abinun, Andrew J. Cant, Andrew R. Gennery. (2009) Unrelated donor and HLA-identical sibling haematopoietic stem cell transplantation cure chronic granulomatous disease with good long-term outcome and growth. British Journal of Haematology 145:1, 73-83
CrossRef39
M.J. Stasia, P. Cathebras, M.-F. Lutz, I. Durieu. (2009) La granulomatose septique chronique. La Revue de Médecine Interne 30:3, 221-232
CrossRef40
PAUL KING, VICKI BENNETT-WOOD, PAUL HUTCHINSON, ROY ROBINS-BROWNE, PETER HOLMES, NICHOLAS FREEZER, STEPHEN HOLDSWORTH. (2009) Bactericidal activity of neutrophils with reduced oxidative burst from adults with bronchiectasis. APMIS 117:2, 133-139
CrossRef41
Brahm H. Segal, Luigina R. Romani. (2009) Invasive aspergillosis in chronic granulomatous disease. Medical Mycology 47:s1, S282-S290
CrossRef42
Sergio D Rosenzweig. (2009) Chronic granulomatous disease: complications and management. Expert Review of Clinical Immunology 5:1, 45-53
CrossRef43
Andrea V Page, W Conrad Liles. (2008) Granulocyte colony-stimulating factor, granulocyte–macrophage colony-stimulating factor, and other immunomodulatory therapies for the treatment of infectious diseases in solid organ transplant recipients. Current Opinion in Organ Transplantation 13:6, 575-580
CrossRef44
Baruch Wolach, Ronit Gavrieli, Martin de Boer, Giora Gottesman, Josef Ben-Ari, Menachem Rottem, Yechiel Schlesinger, Galia Grisaru-Soen, Amos Etzioni, Dirk Roos. (2008) Chronic granulomatous disease in Israel: Clinical, functional and molecular studies of 38 patients. Clinical Immunology 129:1, 103-114
CrossRef45
Barbara A. Castro. (2008) The immunocompromised pediatric patient and surgery. Best Practice & Research Clinical Anaesthesiology 22:3, 611-626
CrossRef46
Adolfo C Fernandez-Obregon, Dhrumil Shah, Amanda I Howell, Imane Tiyal Bentahar, Lester Carrodeguas, Arifa Siddiqui, Julia A Ejiogu. (2008) Challenges in anti-infective therapy for skin conditions: part 1. Expert Review of Dermatology 3:3, 367-394
CrossRef47
Jordan J. Feld, Nadeem Hussain, Elizabeth C. Wright, David E. Kleiner, Jay H. Hoofnagle, Sushil Ahlawat, Victoria Anderson, Dianne Hilligoss, John I. Gallin, T. Jake Liang, Harry L. Malech, Steven M. Holland, Theo Heller. (2008) Hepatic Involvement and Portal Hypertension Predict Mortality in Chronic Granulomatous Disease. Gastroenterology 134:7, 1917-1926
CrossRef48
M. L. Galluzzo, C. Hernandez, M. T. G. Davila, L. Perez, M. Oleastro, M. Zelazko, S. D. Rosenzweig. (2008) Clinical and Histopathological Features and a Unique Spectrum of Organisms Significantly Associated with Chronic Granulomatous Disease Osteomyelitis during Childhood. Clinical Infectious Diseases 46:5, 745-749
CrossRef49
Baldassarre Martire, Roberto Rondelli, Annarosa Soresina, Claudio Pignata, Teresa Broccoletti, Andrea Finocchi, Paolo Rossi, Marco Gattorno, Marco Rabusin, Chiara Azzari, Rosa M. Dellepiane, Maria C. Pietrogrande, Antonino Trizzino, Paolo Di Bartolomeo, Silvana Martino, Luigi Carpino, Fausto Cossu, Franco Locatelli, Rita Maccario, Paolo Pierani, Maria C. Putti, Achille Stabile, Luigi D. Notarangelo, Alberto G. Ugazio, Alessandro Plebani, Domenico De Mattia. (2008) Clinical features, long-term follow-up and outcome of a large cohort of patients with Chronic Granulomatous Disease: An Italian multicenter study. Clinical Immunology 126:2, 155-164
CrossRef50
Thomas J. Walsh, Elias J. Anaissie, David W. Denning, Raoul Herbrecht, Dimitrios P. Kontoyiannis, Kieren A. Marr, Vicki A. Morrison, Brahm H Segal, William J. Steinbach, David A. Stevens, Jo‐Anne van Burik, John R. Wingard, Thomas F. Patterson. (2008) Treatment of Aspergillosis: Clinical Practice Guidelines of the Infectious Diseases Society of America. Clinical Infectious Diseases 46:3, 327-360
CrossRef51
Reinhard A. Seger. (2008) Modern management of chronic granulomatous disease. British Journal of Haematology 140:3, 255-266
CrossRef52
P. A. Mackowiak, H. Heidarnejad, P. Tabarsi, F. Mohammadi, N. Heidarzadeh, M. M. Sajadi, D. Mansouri. (2008) Acute Necrotizing Pneumonia in a Previously Healthy Young Adult. Clinical Infectious Diseases 46:2, 317-319
CrossRef53
Roel Dekkers, Paul E. Verweij, Corry M. R. Weemaes, René S. V. M. Severijnen, Johan H. J. M. Van Krieken, Adilia Warris. (2008) Gastrointestinal zygomycosis due to Rhizopus microsporus var. rhizopodiformis as a manifestation of chronic granulomatous disease. Medical Mycology 46:5, 491-494
CrossRef54
John W. Steinke, Gabor Illei, Gülbû Uzel, JoAnn M. Mican. 2008. Cytokine therapy. , 1393-1404.
CrossRef55
Gülbû Uzel, Steven M. Holland. 2008. Phagocyte deficiencies. , 327-344.
CrossRef56
Andrew S. Kemp. 2008. Congenital Immunodeficiency Syndromes. , 725-734.
CrossRef57
Charalampos Antachopoulos, Thomas J. Walsh, Emmanuel Roilides. (2007) Fungal infections in primary immunodeficiencies. European Journal of Pediatrics 166:11, 1099-1117
CrossRef58
Jacqueline M Achkar, Arturo Casadevall, Aharona Glatman-Freedman. (2007) Immunological options for the treatment of tuberculosis: evaluation of novel therapeutic approaches. Expert Review of Anti-infective Therapy 5:3, 461-474
CrossRef59
Frank Gu, Ronald Neufeld, Brian Amsden. (2007) Sustained release of bioactive therapeutic proteins from a biodegradable elastomeric device. Journal of Controlled Release 117:1, 80-89
CrossRef60
Dirk Roos, Martin de Boer, M. Yavuz Köker, Jan Dekker, Vinita Singh-Gupta, Anders Åhlin, Jan Palmblad, Özden Sanal, Magdalena Kurenko-Deptuch, Stephen Jolles, Baruch Wolach. (2006) Chronic granulomatous disease caused by mutations other than the common GT deletion in NCF1 , the gene encoding the p47 phox component of the phagocyte NADPH oxidase. Human Mutation 27:12, 1218-1229
CrossRef61
Jairam Sastry, Alyson Kakakios, Heidi Tugwell, Peter J. Shaw. (2006) Allogeneic bone marrow transplantation with reduced intensity conditioning for chronic granulomatous disease complicated by invasive Aspergillus infection. Pediatric Blood & Cancer 47:3, 327-329
CrossRef62
Abdul Alsultan, Marc S. Williams, Sam Lubner, Frederick D. Goldman. (2006) Chronic granulomatous disease presenting with disseminated intracranial aspergillosis. Pediatric Blood & Cancer 47:1, 107-110
CrossRef63
J. Mark Donovan, Michael R. Elliott, Daniel F. Heitjan. (2006) Predicting Event Times in Clinical Trials When Treatment Arm Is Masked. Journal of Biopharmaceutical Statistics 16:3, 343-356
CrossRef64
Neeraj Chauhan, Jean-Paul Latge, Richard Calderone. (2006) Signalling and oxidant adaptation in Candida albicans and Aspergillus fumigatus. Nature Reviews Microbiology 4:6, 435-444
CrossRef65
Frank Gu, Ronald Neufeld, Brian Amsden. (2006) Osmotic-Driven Release Kinetics of Bioactive Therapeutic Proteins from a Biodegradable Elastomer are Linear, Constant, Similar, and Adjustable. Pharmaceutical Research 23:4, 782-789
CrossRef66
B. H. Segal, J. Kwon-Chung, T. J. Walsh, B. S. Klein, M. Battiwalla, N. G. Almyroudis, S. M. Holland, L. Romani. (2006) Immunotherapy for Fungal Infections. Clinical Infectious Diseases 42:4, 507-515
CrossRef67
S. Alazemi, M. A. Campos. (2006) Interferon-induced sarcoidosis. International Journal of Clinical Practice 60:2, 201-211
CrossRef68
P. E. Santos, E. Piontelli, Y. R. Shea, M. L. Galluzzo, S. M. Holland, M. E. Zelazko, S. D. Rosenzweig. (2006) Penicillium piceum infection: diagnosis and successful treatment in chronic granulomatous disease. Medical Mycology 44:8, 749-753
CrossRef69
Jessica S. Kosut, Naynesh R. Kamani, Barbara A. Jantausch. (2006) One-Month-Old Infant With Multilobar Round Pneumonias. The Pediatric Infectious Disease Journal 25:1, 95
CrossRef70
2006. Interferon gamma. , 1838-1840.
CrossRef71
Alan P. Knutsen. (2005) Conventional Treatment of Primary Immunodeficiency Disorders. Pediatric Asthma, Allergy & Immunology 18:3, 140-155
CrossRef72
Ernest C. Borden. (2005) Review: Milstein Award Lecture: Interferons and Cancer: Where from Here?. Journal of Interferon & Cytokine Research 25:9, 511-527
CrossRef73
Hongkui Jin, Wei Li, Renhui Yang, Annie Ogasawara, Hsienwie Lu, Nicholas F. Paoni. (2005) Inhibitory effects of interferon-γ on myocardial hypertrophy. Cytokine 31:6, 405-414
CrossRef74
Srinivasan Ramanuja, Karen M. Wolf, Mohammed A. Sadat, Stephen J. Mahoney, Mary C. Dinauer, Robert P. Nelson. (2005) Newly diagnosed chronic granulomatous disease in a 53-year-old woman with Crohn disease. Annals of Allergy, Asthma & Immunology 95:2, 204-209
CrossRef75
B. H. Segal, L. A. Barnhart, V. L. Anderson, T. J. Walsh, H. L. Malech, S. M. Holland. (2005) Posaconazole as Salvage Therapy in Patients with Chronic Granulomatous Disease and Invasive Filamentous Fungal Infection. Clinical Infectious Diseases 40:11, 1684-1688
CrossRef76
Charalampos Antachopoulos, Emmanuel Roilides. (2005) Cytokines and fungal infections. British Journal of Haematology 129:5, 583-596
CrossRef77
Tayfun G??ng??r, J??rg Halter, Anne Klink, Sonja Junge, Katrin D. M. Stumpe, Reinhard Seger, Urs Schanz. (2005) Successful Low Toxicity Hematopoietic Stem Cell Transplantation for High-Risk Adult Chronic Granulomatous Disease Patients. Transplantation 79:11, 1596-1606
CrossRef78
Shigeyuki Matsui. (2005) Sample size calculations for comparative clinical trials with over-dispersed Poisson process data. Statistics in Medicine 24:9, 1339-1356
CrossRef79
Francisco A. Bonilla, I. Leonard Bernstein, David A. Khan, Zuhair K. Ballas, Javier Chinen, Michael M. Frank, Lisa J. Kobrynski, Arnold I. Levinson, Bruce Mazer, Robert P. Nelson, Jordan S. Orange, John M. Routes, William T. Shearer, Ricardo U. Sorensen. (2005) Practice parameter for the diagnosis and management of primary immunodeficiency. Annals of Allergy, Asthma & Immunology 94:5, S1-S63
CrossRef80
Fernanda Silveira, David L Paterson. (2005) Pulmonary fungal infections. Current Opinion in Pulmonary Medicine 11:3, 242-246
CrossRef81
E RICHARD STIEHM, RICHARD B. JOHNSTON. (2005) A History of Pediatric Immunology. Pediatric Research 57:3, 458-467
CrossRef82
Lukela, Michael, DeGuzman, David, Weinberger, Steven, Saint, Sanjay, . (2005) Unfashionably Late. New England Journal of Medicine 352:1, 64-69
Full Text83
N. G. Almyroudis, S. M. Holland, B. H. Segal. (2005) Invasive aspergillosis in primary immunodeficiencies. Medical Mycology 43:s1, 247-259
CrossRef84
Takuhiro Yamaguchi. (2005) Recurrent Events Data Analysis: A Review. Japanese Journal of Biometrics 26:2, 81-117
CrossRef85
A. Grassegger, R. Hopfl. (2004) Significance of the cytokine interferon gamma in clinical dermatology. Clinical and Experimental Dermatology 29:6, 584-588
CrossRef86
Ferric C. Fang. (2004) Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nature Reviews Microbiology 2:10, 820-832
CrossRef87
Dennis J. Cotter, Kevin Stefanik, Yi Zhang, Mae Thamer, Daniel Scharfstein, James Kaufman. (2004) Hematocrit was not validated as a surrogate end point for survival among epoetin-treated hemodialysis patients. Journal of Clinical Epidemiology 57:10, 1086-1095
CrossRef88
B. E. Marciano, R. Wesley, E. S. De Carlo, V. L. Anderson, L. A. Barnhart, D. Darnell, H. L. Malech, J. I. Gallin, S. M. Holland. (2004) Long-Term Interferon- Therapy for Patients with Chronic Granulomatous Disease. Clinical Infectious Diseases 39:5, 692-699
CrossRef89
Jeannie S Huang, Deborah Noack, Julie Rae, Beverly A Ellis, Robert Newbury, Alice L Pong, Joel E Lavine, John T Curnutte, John Bastian. (2004) Chronic granulomatous disease caused by a deficiency in p47phox mimicking Crohn’s disease. Clinical Gastroenterology and Hepatology 2:8, 690-695
CrossRef90
Y. Zhang. (2004) Does dose matter?. Nephrology Dialysis Transplantation 19:6, 1658-1658
CrossRef91
M. Kharfi, R. Benmously, A. Khaled, B. Daoued, M.-R. Kamoun. (2004) Granulomatose septique chronique à révélation cutanée tardive. Annales de Dermatologie et de Vénéréologie 131:4, 375-378
CrossRef92
Timothy T. Kuberski, Ronald J. Servi, Phillip J. Rubin. (2004) Successful Treatment of a Critically Ill Patient with Disseminated Coccidioidomycosis, Using Adjunctive Interferon‐γ. Clinical Infectious Diseases 38:6, 910-912
CrossRef93
Xiaogang Su, Juanjuan Fan. (2004) Multivariate Survival Trees: A Maximum Likelihood Approach Based on Frailty Models. Biometrics 60:1, 93-99
CrossRef94
Christian Schinkel. (2003) The Role of IFN-γ in Surgical Patients. Journal of Interferon & Cytokine Research 23:7, 341-349
CrossRef95
Gallin, John I., Alling, David W., Malech, Harry L., Wesley, Robert, Koziol, Deloris, Marciano, Beatriz, Eisenstein, Eli M., Turner, Maria L., DeCarlo, Ellen S., Starling, Judith M., Holland, Steven M., . (2003) Itraconazole to Prevent Fungal Infections in Chronic Granulomatous Disease. New England Journal of Medicine 348:24, 2416-2422
Full Text96
Emmanuel Roilides, Caron A Lyman, Paraskevi Panagopoulou, Stephen Chanock. (2003) Immunomodulation of invasive fungal infections. Infectious Disease Clinics of North America 17:1, 193-219
CrossRef97
Meredith Heltzer, Abbas F. Jawad, Julie Rae, John T. Curnutte, Kathleen E. Sullivan. (2002) Diminished T Cell Numbers in Patients with Chronic Granulomatous Disease. Clinical Immunology 105:3, 273-278
CrossRef98
Eva-Maria Wolber, Berit Haase, Wolfgang Jelkmann. (2002) Short Communication: Thrombopoietin Production in Human Hepatic Cell Cultures (HepG2) Is Resistant to IFN- α , IFN- β , and IFN- γ Treatment. Journal of Interferon & Cytokine Research 22:12, 1185-1189
CrossRef99
G. Lyratzopoulos, M. Ellis, R. Nerringer, D.W. Denning. (2002) Invasive Infection due to Penicillium Species other than P. marneffei. Journal of Infection 45:3, 184-195
CrossRef100
Emmanuel Roilides, Cristina Gil Lamaignere, Evangelia Farmaki. (2002) Cytokines in immunodeficient patients with invasive fungal infections: an emerging therapy. International Journal of Infectious Diseases 6:3, 154-163
CrossRef101
Marion-Gabriele Ott, Heike Merget-Millitzer, Oliver Gerhard Ottmann, Hans Martin, Nicole Bruggenolte, Heike Bialek, Reinhard Seger, Johann Peter Hossle, Dieter Hoelzer, Manuel Grez. (2002) Mobilization and Transduction of CD34+ Peripheral Blood Stem Cells in Patients with X-Linked Chronic Granulomatous Disease. Journal of Hematotherapy <html_ent glyph="@amp;" ascii="&"/> Stem Cell Research 11:4, 683-694
CrossRef102
George Nakos, Vasiliki D. Malamou-Mitsi, Alexandra Lachana, Aikaterini Karassavoglou, Eirini Kitsiouli, Niki Agnandi, Marilena E. Lekka. (2002) Immunoparalysis in patients with severe trauma and the effect of inhaled interferon-γ*. Critical Care Medicine 30:7, 1488-1494
CrossRef103
Susan S. Ellenberg. (2001) Surrogate endpoints: the debate goes on. Pharmacoepidemiology and Drug Safety 10:6, 493-496
CrossRef104
Peter D. Reuman. (2001) Immunomodulators. The Pediatric Infectious Disease Journal 20:10, 995-996
CrossRef105
R. J. Rentenaar, J. De Metz, M. Bunders, P. M. E. Wertheim-Van Dillen, D. J. Gouma, J. A. Romijn, H. P. Sauerwein, I. J. M. TEN BERGE, R. A. W. Van Lier. (2001) Interferon-gamma administration after abdominal surgery rescues antigen-specific helper T cell immune reactivity. Clinical and Experimental Immunology 125:3, 401-408
CrossRef106
KUENDER D. YANG, HARRY R. HILL. (2001) Granulocyte function disorders: aspects of development, genetics and management. The Pediatric Infectious Disease Journal 20:9, 889-900
CrossRef107
Sharon H. Jackson, Georgina F. Miller, Brahm H. Segal, Michael Mardiney, Joseph B. Domachowske, John I. Gallin, Steven M. Holland. (2001) IFN- γ Is Effective in Reducing Infections in the Mouse Model of Chronic Granulomatous Disease (CGD). Journal of Interferon & Cytokine Research 21:8, 567-573
CrossRef108
Emilia Bagiella, Daniel F. Heitjan. (2001) Predicting analysis times in randomized clinical trials. Statistics in Medicine 20:14, 2055-2063
CrossRef109
Pascal Cathébras, Catherine Sauron, Françoise Morel, Marie-José Stasia. (2001) An unusual case of sarcoidosis. The Lancet 358:9278, 294
CrossRef110
Lynn A. Riddell, Anthony J. Pinching, Susan Hill, Tony T. Ng, Emilio Arbe, Gary P. Lapham, Stephen Ash, Richard Hillman, Stephen Tchamouroff, David W. Denning, Jacqueline M. Parkin. (2001) A Phase III Study of Recombinant Human Interferon Gamma to Prevent Opportunistic Infections in Advanced HIV Disease. AIDS Research and Human Retroviruses 17:9, 789-797
CrossRef111
Sanjay Sangwan, Subrata Sarkar. (2001) Chronic Granulomatous Disease. Pediatric Asthma, Allergy & Immunology 15:2, 113-116
CrossRef112
Jacqueline Parkin, Bryony Cohen. (2001) An overview of the immune system. The Lancet 357:9270, 1777-1789
CrossRef113
F. T. Saulsbury. (2001) Successful Treatment of Aspergillus Brain Abscess with Itraconazole and Interferon- in a Patient with Chronic Granulomatous Disease. Clinical Infectious Diseases 32:10, e137-e139
CrossRef114
Nathalie D. Burg, Michael H. Pillinger. (2001) The Neutrophil: Function and Regulation in Innate and Humoral Immunity. Clinical Immunology 99:1, 7-17
CrossRef115
Ezekowitz, R. Alan B., . (2001) What is the Best Way to Treat Inherited Disorders?. New England Journal of Medicine 344:12, 926-927
Full Text116
Horwitz, Mitchell E., Barrett, A. John, Brown, Margaret R., Carter, Charles S., Childs, Richard, Gallin, John I., Gress, Ronald E., Holland, Steven M., Linton, Gilda F., Miller, Judi A., Leitman, Susan F., Read, Elizabeth J., Schermerhorn, James, Malech, Harry L., . (2001) Treatment of Chronic Granulomatous Disease with Nonmyeloablative Conditioning and a T-Cell–Depleted Hematopoietic Allograft. New England Journal of Medicine 344:12, 881-888
Full Text117
B. Spellberg, J. E. Edwards. (2001) Type 1/Type 2 Immunity in Infectious Diseases. Clinical Infectious Diseases 32:1, 76-102
CrossRef118
Mackay, Ian R., Rosen, Fred S., , Lekstrom-Himes, Julie A., Gallin, John I., . (2000) Immunodeficiency Diseases Caused by Defects in Phagocytes. New England Journal of Medicine 343:23, 1703-1714
Full Text119
R. S. Weening, M. De Boer, T. W. Kuijpers, V. M. E. Neefjes, W. W. M. Hack, D. Roos. (2000) Point mutations in the promoter region of the CYBB gene leading to mild chronic granulomatous disease. Clinical and Experimental Immunology 122:3, 410-417
CrossRef120
Steven M Holland. (2000) Treatment of infections in the patient with Mendelian susceptibility to mycobacterial infection. Microbes and Infection 2:13, 1579-1590
CrossRef121
D. Goldblatt, A. J. Thrasher. (2000) Chronic granulomatous disease. Immunodeficiency review. Clinical and Experimental Immunology 122:1, 1-9
CrossRef122
Julia A. Piwoz, Gary J. Stadtmauer, Edward J. Bottone, Irene Weitzman, Edward Shlasko, Charlotte Cunningham-Rundles. (2000) TRICHOSPORON INKIN LUNG ABSCESSES PRESENTING AS A PENETRATING CHEST WALL MASS. The Pediatric Infectious Disease Journal 19:10, 1025-1027
CrossRef123
E. Graham Davies. (2000) Infection in patients with primary immunodeficiency disorders. Current Opinion in Infectious Diseases 13:4, 349-353
CrossRef124
Yiannis Ioannou, David A. Isenberg. (2000) Current evidence for the induction of autoimmune rheumatic manifestations by cytokine therapy. Arthritis & Rheumatism 43:7, 1431-1442
CrossRef125
C. M. Cale, A. M. Jones, D. Goldblatt. (2000) Follow up of patients with chronic granulomatous disease diagnosed since 1990. Clinical and Experimental Immunology 120:2, 351-355
CrossRef126
Brahm H Segal, Thomas L Leto, John I Gallin, Harry L Malech, Steven M Holland. (2000) Genetic, Biochemical, and Clinical Features of Chronic Granulomatous Disease. Medicine 79:3, 170-200
CrossRef127
S. Martino, M. Ciocchini, A. Marmont, E. Madon, P.-A. Tovo. (2000) Treatment of Hepatic Abscesses in Chronic Granulomatous Disease with Granulocyte-Macrophage Colony-Stimulating Factor. Clinical Infectious Diseases 30:1, 222-223
CrossRef128
J. R. Graybill, J. Tollemar, J. M. Torres-Rodríguez, T. J. Walsh, E. Roilides, E. Farmaki. (2000) Antifungal compounds: controversies, queries and conclusions. Medical Mycology 38:s1, 323-333
CrossRef129
Borna Mehrad, Theodore J. Standiford. (1999) Role of cytokines in pulmonary antimicrobial host defense. Immunologic Research 20:1, 15-27
CrossRef130
Dario Conte, Mirella Fraquelli, Franco Capsoni, Mauro Giacca, Lorena Zentilin, Maria Teresa Bardella. (1999) Effectiveness of IFN-gamma for Liver Abscesses in Chronic Granulomatous Disease. Journal of Interferon & Cytokine Research 19:7, 705-710
CrossRef131
Sean P. Elliott, Susan B. Mallory. (1999) SWEET SYNDROME: AN UNUSUAL PRESENTATION OF CHRONIC GRANULOMATOUS DISEASE IN A CHILD. The Pediatric Infectious Disease Journal 18:6, 568-570
CrossRef132
Hassib Narchi, Sultan Gammoh. (1999) MULTIPLE NODULAR PNEUMONITIS IN A THREE-WEEK-OLD FEMALE INFANT. The Pediatric Infectious Disease Journal 18:5, 471
CrossRef133
Ashish Jain, T. Prescott Atkinson, Peter E. Lipsky, Jay E. Slater, David L. Nelson, Warren Strober. (1999) Defects of T-cell effector function and post-thymic maturation in X-linked hyper-IgM syndrome. Journal of Clinical Investigation 103:8, 1151-1158
CrossRef134
David L. Paterson, Nina Singh. (1999) Invasive Aspergillosis in Transplant Recipients. Medicine 78:2, 123-138
CrossRef135
Brahm H. Segal, Ellen S. DeCarlo, K. J. Kwon-Chung, Harry L. Malech, John I. Gallin, Steven M. Holland. (1998) Aspergillus nidulans Infection in Chronic Granulomatous Disease. Medicine 77:5, 345-354
CrossRef136
JOS W.M. MEER, MARIA T.E. VOGELS, MIHAI G. NETEA, BART JAN KULLBERG. (1998) Proinflammatory Cytokines and Treatment of Disease. Annals of the New York Academy of Sciences 856:1 MOLECULAR MEC, 243-251
CrossRef137
DAVID J. DRIES, JEANINE M. WALENGA, DEBRA HOPPENSTEADT, JAWED FAREED. (1998) Molecular Markers of Hemostatic Activation and Inflammation Following Major Injury: Effect of Therapy with IFN-γ. Journal of Interferon & Cytokine Research 18:5, 327-335
CrossRef138
Gleave, Martin E.Elhilali, MostafaFradet, YvesDavis, IanVenner, PeterSaad, FredKlotz, Laurence H.Moore, Malcolm J.Paton, VirginiaBajamonde, AlexBell, DavidErnst, ScottRamsey, ErnestChin, JoeMorales, AlvaroMartins, HeidiSanders, Coreethe Canadian Urologic Oncology Group. (1998) Interferon Gamma-1b Compared with Placebo in Metastatic Renal-Cell Carcinoma. New England Journal of Medicine 338:18, 1265-1271
Full Text139
Dana Kosmala, Donald Janner. (1998) PERSISTENT FEVER, PSEUDOMONAS PNEUMONIA AND GRAM-NEGATIVE SEPTICEMIA IN A THREE-YEAR-OLD MALE CHILD. The Pediatric Infectious Disease Journal 17:3, 263-264
CrossRef140
Steven M. Holland, MD, John I. Gallin, MD. (1998) EVALUATION OF THE PATIENT WITH RECURRENT BACTERIAL INFECTIONS 1 1. Annual Review of Medicine 49:1, 185-199
CrossRef141
Kohichiro Tsuji, Kenji Muraoka, Tatsutoshi Nakahata. (1998) Interferon-γ and Human Megakaryopoiesis. Leukemia & Lymphoma 31:1-2, 107-113
CrossRef142
J. Lohmeyer. (1997) Role of hemopoietic growth factors and cytokines in host defense against fungal infections. Mycoses 40, 37-39
CrossRef143
Scott H. Sicherer, Edwin J. Asturias, Jerry A. Winkelstein, James D. Dick, Rodney E. Willoughby. (1997) FRANCISELLA PHILOMIRAGIA SEPSIS IN CHRONIC GRANULOMATOUS DISEASE. The Pediatric Infectious Disease Journal 16:4, 420-422
CrossRef144
Brian J. Broker, David Rosen, James Amsberry, Richard Schmidt, Linda Sailor, Edmund A. Pribitkin, William M. Keane. (1996) Keloid Excision and Recurrence Prophylaxis Via Intradermal Interferon-Gamma Injections: A Pilot Study. The Laryngoscope 106:12, 1497-1501
CrossRef145
H. W. Murray. (1996) Current and future clinical applications of interferon-gamma in host antimicrobial defense. Intensive Care Medicine 22:S4, S456-S461
CrossRef146
David J. Dries. (1996) Interferon gamma in trauma-related infections. Intensive Care Medicine 22:S4, S462-S467
CrossRef147
Jeanine L. Bussiere, Laurel M. Hardy, Alan M. Hoberman, John A. Foss, Mildred S. Christian. (1996) Reproductive effects of chronic administration of murine interferon-gamma. Reproductive Toxicology 10:5, 379-391
CrossRef148
Srdjan Pasic, Mario Abinun, Boris Pistignjat, Bozidar Vlajic, Jelena Rakic, Ljudmila Sarjanovic, Nikola Ostojic. (1996) ASPERGILLUS OSTEOMYELITIS IN CHRONIC GRANULOMATOUS DISEASE: TREATMENT WITH RECOMBINANT GAMMA-INTERFERON AND ITRACONAZOLE. The Pediatric Infectious Disease Journal 15:9, 833-834
CrossRef149
Andrea Abati, Agustin Cajigas, Steven M. Holland, Diane Solomon. (1996) Chronic granulomatous disease of childhood: Respiratory cytology. Diagnostic Cytopathology 15:2, 98-102
CrossRef150
Raymond Vanholder, Norbert Lameire, Marie Anne Waterloos, Nadine van Landschoot, Rita de Smet, Pascale Vogeleere, Marie Christine Lambert, Denise Vijt, Severin Ringoir. (1996) Disturbed host defense in peritoneal cavity during CAPD: Characterization of responsible factors in dwell fluid. Kidney International 50:2, 643-652
CrossRef151
ALLAN S. LAU, DEBORAH LEHMAN, FRANCESCA R. GEERTSMA, MICHAEL C. YEUNG. (1996) Biology and therapeutic uses of myeloid hematopoietic growth factors and interferons. The Pediatric Infectious Disease Journal 15:7, 563-575
CrossRef152
John R. Wingard, Gerald J. Elfenbein. (1996) HOST IMMUNOLOGIC AUGMENTATION FOR THE CONTROL OF INFECTION. Infectious Disease Clinics of North America 10:2, 345-364
CrossRef153
Stephen J. Chanock, Jed B. Gorlin. (1996) GRANULOCYTE TRANSFUSIONS. Infectious Disease Clinics of North America 10:2, 327-343
CrossRef154
ANTONIO CONDINO-NETO, MARCELO N. MUSCARÁ, RAQUEL BELLINATI-PIRES, MAGDA M.S. CARNEIRO-SAMPAIO, ANA C. BRANDÃO, ANETE S. GRUMACH, GILBERTO DE NUCCI. (1996) Effect of Therapy with Recombinant Human Interferon-γ on the Release of Nitric Oxide by Neutrophils and Mononuclear Cells from Patients with Chronic Granulomatous Disease. Journal of Interferon & Cytokine Research 16:5, 357-364
CrossRef155
J Liese, A Jansson, Th Petropoulou, S Kloos, B.H Belohradsky, V Jendrossek, M Gahr. (1996) Chronic granulomatous disease in adults. The Lancet 347:8996, 220-223
CrossRef156
A Åhlin, M Boer, D Roos, J Leusen, CIE Smith, U Sundin, H Rabbani, J Palmblad, G Elinder. (1995) Prevalence, genetics and clinical presentation of chronic granulomatous disease in Sweden. Acta Paediatrica 84:12, 1386-1394
CrossRef157
Mark P. Yeager, Thomas A. Colacchio, Cecelia T. Yu, Laurie Hildebrandt, Alexandra L. Howell, Julie Weiss, Paul M. Guyre. (1995) Morphine Inhibits Spontaneous and Cytokine-enhanced Natural Killer Cell Cytotoxicity in Volunteers. Anesthesiology 83:3, 500-508
CrossRef158
V. Bogomolski-Yahalom, Y. Matzner. (1995) Disorders of neutrophil function. Blood Reviews 9:3, 183-190
CrossRef159
SHOUICHI OHGA, JUN OKAMURA, HIDEKI NAKAYAMA, YOSHIHISA NAGATOSHI, KOHJI UEDA. (1995) Interferon-γ therapy for infection control in chronic granulomatous disease. Pediatrics International 37:3, 315-320
CrossRef160
P. P. Hujoel, T. A. DeRouen. (1995) A survey of endpoint characteristics in periodontal clinical trials published 1988-1992, and implications for future studies. Journal of Clinical Periodontology 22:5, 397-407
CrossRef161
R. S. Weening, G. J. Leitz, R. A. Seger. (1995) Recombinant human interferon-gamma in patients with chronic granulomatous disease —European follow up study. European Journal of Pediatrics 154:4, 295-298
CrossRef162
Jordan W. Eckert, Stuart L. Abramson, Jeffrey Starke, Mary L. Brandt. (1995) The surgical implications of chronic granulomatous disease. The American Journal of Surgery 169:3, 320-323
CrossRef163
A. Cohen-Abbo, Kathryn M. Edwards. (1995) Multifocal osteomyelitis caused byPaecilomyces varioti in a patient with chronic granulomatous disease. Infection 23:1, 55-57
CrossRef164
Bart -Jan Kullberg, Jan W. Wout. (1994) Cytokines in the treatment of fungal infections. Biotherapy 7:3-4, 195-210
CrossRef165
Benjamin A. Kruskal, R. Alan B. Ezekowitz. (1994) Cytokines in the treatment of primary immunodeficiency. Biotherapy 7:3-4, 249-259
CrossRef166
John L. Ho, Roberto Badaro, Dimitrios Hatzigeorgiou, Steven G. Reed, Warren D. Johnson. (1994) Cytokines in the treatment of leishmaniasis: From studies of immunopathology to patient therapy. Biotherapy 7:3-4, 223-235
CrossRef167
S. Umeki. (1994) Mechanisms for the activation/electron transfer of neutrophil NADPH-oxidase complex and molecular pathology of chronic granulomatous disease. Annals of Hematology 68:6, 267-277
CrossRef168
Holland, Steven M.Eisenstein, Eli M.Kuhns, Douglas B.Turner, Maria L.Fleisher, Thomas A.Strober, WarrenGallin, John I.. (1994) Treatment of Refractory Disseminated Nontuberculous Mycobacterial Infection With Interferon Gamma: A Preliminary Report. New England Journal of Medicine 330:19, 1348-1355
Full Text169
David W. Denning. (1994) Treatment of invasive aspergillosis. Journal of Infection 28, 25-33
CrossRef170
Dirk Roos. (1994) The Genetic Basis of Chronic Granulomatous Disease. Immunological Reviews 138:1, 121-157
CrossRef171
J. Lunzen, J. Schmitz, J. Brazoska, Sabine Flessenkämper, M. Dietrich, P. Kern. (1993) Short term treatment of visceral leishmaniasis of the old world with low dose interferon gamma and pentavalent antimony. Infection 21:6, 362-366
CrossRef172
A. Fischer, A. W. Segal, R. Seger, R. S. Weening. (1993) The management of chronic granulomatous disease. European Journal of Pediatrics 152:11, 896-899
CrossRef173
A. S. KEMP. (1993) Interferon therapy in paediatric practice: New applications. Journal of Paediatrics and Child Health 29:5, 328-330
CrossRef174
Cabot, Richard C.Scully, Robert E., Mark, Eugene J., McNeely, William F., McNeely, Betty U., Klein, Jerome O.Mattia, Anthony R.. (1993) Case 35-1993. New England Journal of Medicine 329:10, 714-721
Full Text175
M. BOGUNIEWICZ, L. C. SCHNEIDER, H. MLLGROM, D. NEWELL, N. KELLY, P. TAM, A. E. IZU, H. S. JAFFE, L. R. BUCALO, D. Y. M. LEUNG. (1993) Treatment of steroid-dependent asthma with recombinant interferon-gamma. Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy 23:9, 785-790
CrossRef176
Wood, Alastair J.J., , Pizzo, Philip A.. (1993) Management of Fever in Patients with Cancer and Treatment-Induced Neutropenia. New England Journal of Medicine 328:18, 1323-1332
Full Text177
Helen W. Pogrebniak, John I. Gallin, Harry L. Malech, Alan R. Baker, Christopher A. Moskaluk, William D. Travis, Harvey I. Pass. (1993) Surgical management of pulmonary infections in chronic granulomatous disease of childhood. The Annals of Thoracic Surgery 55:4, 844-849
CrossRef178
Thomas R. Fleming. (1993) Data monitoring committees and capturing relevant information of high quality. Statistics in Medicine 12:5-6, 565-570
CrossRef179
GUNDEL HARMS, KAI ZWINGENBERGER, BEATE SANDKAMP, SIMONE OMENA, CELIA PEDROSA, JOACHIM RICHTER, FRANK ROSENKAIMER, HERMANN FELDMEIER, ULRICH BIENZLE. (1993) Immunochemotherapy of Visceral Leishmaniasis: A Pilot Trial of Sequential Treatment with Recombinant Interferon-γ and Pentavalent Antimony. Journal of Interferon Research 13:1, 39-41
CrossRef180
M. Aoun, J. Klastersky. (1993) Respiratory infections in the immunocompromised patient. International Journal of Antimicrobial Agents 3, S99-S108
CrossRef181
S. Oez, J. Birkmann, J. R. Kalden. (1993) Clonal growth of functionally normal and deficient neutrophils from the bone marrow of a patient with variant chronic granulomatous disease. Annals of Hematology 66:1, 21-25
CrossRef182
CHRISTINE W. CZARNIECKI, GERALD SONNENFELD. (1993) Interferon-gamma and resistance to bacterial infections. APMIS 101:1-6, 1-17
CrossRef183
David M. Allen, Hiok Hee Chng. (1993) Disseminated Mycobacterium flavescens in a probable case of chronic granulomatous disease. Journal of Infection 26:1, 83-86
CrossRef184
Yorikazu Ishikawa, Motohiko Okano, Hideki Arioka, Ryoji Kobayashi, Hiroyuki Naito, Yukio Sakiyama. (1993) Painless and Safe Subcutaneous Catheter for Injection of Various Cytokines in Patients with Hematological Disorders. Pediatric Hematology-Oncology 10:2, 205-206
CrossRef185
James D. Green, Timothy G. Terrell. (1992) Utilization of homologous proteins to evaluate the safety of recombinant human proteins — case study: recombinant human interferon-gamma (rhIFN-γ). Toxicology Letters 64-65, 321-327
CrossRef186
J. R. Hobbs, M. Monteil, D. R. McCluskey, E. Jurges, M. Tumi. (1992) Chronic granulomatous disease 100% corrected by displacement bone marrow transplantation from a volunteer unrelated donor. European Journal of Pediatrics 151:11, 806-810
CrossRef187
HENRY W. MURRAY. (1992) The Interferons, Macrophage Activation, and Host Defense Against Nonviral Pathogens. Journal of Interferon Research 12:5, 319-322
CrossRef188
B. C. M. J. Takx-Köhlen. (1992) Immunomodulators. Pharmaceutisch Weekblad Scientific Edition 14:4, 245-252
CrossRef189
Steven A. Teich, Tony W. Cheung, Alan H. Friedman. (1992) Systemic antiviral drugs used in ophthalmology. Survey of Ophthalmology 37:1, 19-53
CrossRef190
Borden, Ernest C., . (1992) Interferons — Expanding Therapeutic Roles. New England Journal of Medicine 326:22, 1491-1493
Full Text191
JAN M. AGOSTI, ROBERT W. COOMBS, ANN C. COLLIER, MARY A. PARADISE, JACQUELINE K. BENEDETTI, HOWARD S. JAFFE, LAWRENCE COREY. (1992) A Randomized, Double-Blind, Phase I/II Trial of Tumor Necrosis Factor and Interferon-Gamma for Treatment of AIDS-Related Complex (Protocol 025 from the AIDS Clinical Trials Group). AIDS Research and Human Retroviruses 8:5, 581-587
CrossRef192
Hiram C. Polk, William G. Cheadle, David H. Livingston, Jorge L. Rodriguez, Karen M. Starko, Allen E. Izu, Howard S. Jaffe, Gerald Sonnenfeld. (1992) A randomized prospective clinical trial to determine the efficacy of interferon-γ in severely injured patients. The American Journal of Surgery 163:2, 191-196
CrossRef193
R. A. Seger, F. Berthet, J. P. Hossie. (1992) Chronic granulomatous disease. Pediatric Allergy and Immunology 3:1, 1-10
CrossRef194
Mary Ellen Conley. (1992) Genetic immunodeficiencies: both the lumpers and the splitters can claim victory. Current Opinion in Immunology 4:4, 490-493
CrossRef195
Schapiro, Brian L., Newburger, Peter E., Klempner, Mark S., Dinauer, Mary C., . (1991) Chronic Granulomatous Disease Presenting in a 69-Year-Old Man. New England Journal of Medicine 325:25, 1786-1790
Full Text196
(1991) Interferon Gamma for Chronic Granulomatous Disease. New England Journal of Medicine 325:21, 1516-1517
Full Text197
Francoise MOREL, Jacques DOUSSIERE, Pierre V. VIGNAIS. (1991) The superoxide-generating oxidase of phagocytic cells. Physiological, molecular and pathological aspects. European Journal of Biochemistry 201:3, 523-546
CrossRef198
(1991) Granulomas and cytokines. The Lancet 337:8749, 1067-1069
CrossRef
- Letters
