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Melvin Berger

Publications and source records attributed to Melvin Berger.

16 recordsLinked to original sources
PubMed2006

Health-related quality of life and treatment satisfaction in North American patients with primary immunedeficiency diseases receiving subcutaneous IgG self-infusions at home.

The lifelong IgG replacement therapy for patients with primary immunedeficiencies (PIDD) may be provided by intravenous (IVIG) or by subcutaneous IgG (SCIG) infusions. We investigated the impact of weekly SCIG self-infusions at home on the health-related quality of life, treatment satisfaction, and preferences in patients treated with IVIG at the hospital/doctor's office (Group A) or at home (Group B) before the study started. Forty-four adult North American PIDD patients were included in the study, 28 patients in Group A and 16 in Group B. Patients in Group A reported significantly less limitations with their work/daily activities, a significantly improved vitality, and better general health. Treatment satisfaction was significantly improved in Group A. The preference for the subcutaneous route and for home therapy was respectively 81% and 90% in Group A. In Group B, 69% preferred the subcutaneous route and 92% home therapy.

Adult↗
PubMed2005

Why HAE?

Explore the source record for details and available documents.

Angioedema↗
PubMed2005

Role of IL-10 deficiency in excessive nuclear factor-kappaB activation and lung inflammation in cystic fibrosis transmembrane conductance regulator knockout mice.

BACKGROUND: Patients with cystic fibrosis (CF) and CF transmembrane conductance regulator knockout (CF-KO) mice are deficient in pulmonary IL-10 and have excessive inflammatory response to Pseudomonas aeruginosa infection. OBJECTIVE: We hypothesized that local IL-10 deficiency in the lung was responsible for prolonged and excessive inflammatory responses and observations of inflammation in the absence of infection. METHODS: To determine whether IL-10 deficiency could account for persistent inflammation in CF mice independent of interactions of bacteria with epithelial cells, we challenged IL-10-knockout (IL-10-KO), CF-KO, and wild-type (WT) mice intratracheally with LPS and determined the effects of IL-10 replacement in CF-KO mice. RESULTS: In response to LPS, IL-10-KO and CF-KO mice had more neutrophils and proinflammatory cytokines in bronchoalveolar lavage than WT mice. Both types of knockout mice had more profound and prolonged consumption of I-kappaB and increased activation of nuclear factor kappaB (NF-kappaB). Activated NF-kappaB persisted for 6 to 8 hours in CF-KO and IL-10-KO mice but was not detected beyond 2 hours in WT mice. IL-10 treatment of CF-KO mice attenuated the reduction in I-kappaBalpha and activation of NF-kappaB and reduced the excessive inflammation. CONCLUSION: Similarities in the responses of CF-KO and IL-10-KO mice and correction of excessive responses in CF mice by exogenous IL-10 suggest that deficiency of IL-10 may be responsible for prolonged and excessive inflammatory responses in CF. Because LPS was used as the stimulus, these excessive responses are independent of any possible differences in the interactions of bacteria with CF epithelial cells.

Animals↗
PubMed2004

Subcutaneous immunoglobulin replacement in primary immunodeficiencies.

The use of small portable pumps for subcutaneous infusion of IgG in patients with primary immunodeficiencies was introduced more than 20 years ago. In the US, i.v.i.g. became more popular, but in other countries, many patients use the subcutaneous route. Pharmacokinetics of IgG differ when smaller doses are given more frequently, as is commonly done with subcutaneous regimens, as compared to the large boluses given every 21-28 days in most i.v. regimens. Differences include lower peaks and higher troughs, which may be preferable for some patients. Advantages of the subcutaneous route include increased patient autonomy, decreased systemic adverse effects, and the lack of a requirement for vascular access. Disadvantages include limitation in the volume that can be administered at any one time, necessitating frequent dosing; and the requirement for reliability if a patient is to self or home infuse. Obstacles may be encountered because no preparation of IgG is currently licensed for subcutaneous use in the US. Subcutaneous IgG replacement may be preferable to i.v. infusions or i.m. injections for carefully selected patients.

Adult↗
PubMed2004

Safety, efficacy, and pharmacokinetics of Flebogamma 5% [immune globulin intravenous (human)] for replacement therapy in primary immunodeficiency diseases.

The purpose of the study was to evaluate the safety, efficacy, and pharmacokinetics of Flebogamma 5%, an immune globulin intravenous product, for replacement therapy in primary immunodeficient patients. The US Food and Drug Administration has proposed that the use of new products must result in < or =1 serious bacterial infection/subject/year, have acceptable safety and tolerability, and have pharmacokinetic properties similar to endogenous IgG and other commercially available immune globulin products. Flebogamma 5% was administered at seven clinical sites to 51 subjects aged 14-74 years with well-defined primary immunodeficiency diseases at a dose of 300-600 mg/kg every 21-28 days for 12 months. The calculated serious infection rate for the intent-to-treat population was 0.061/subject/year. The incidence of adverse events considered potentially related to Flebogamma 5%, and occurring during or within 72 h after completing the infusion was approximately 8%. The half-life of total IgG was 37 days. Flebogamma 5% is efficacious, safe, and well-tolerated, and does not put subjects at increased risk of adverse events other than those that could be reasonably expected in primary immunodeficient subjects who are receiving any immune globulin product.

Adolescent↗
PubMed2003

Development and validation of school-based asthma and allergy screening instruments for parents and students.

BACKGROUND: The increasing morbidity attributable to asthma among school-aged children suggests the potential utility of school-based asthma screening programs. OBJECTIVE: We report our efforts to develop and validate culturally sensitive and clinically useful screening questionnaires (parent and child versions) for asthma and allergies among urban US school children. METHODS: Instrument development was accomplished through literature review, expert medical and child developmental input, focus group feedback, and a rigorous trial of the instruments in a public school setting. Questionnaires were distributed to 2,800 children and their families in an urban public school system (grades kindergarten through 6). Validity was evaluated by blinded comparison of results against a standardized clinical evaluation in 107 children, with final designations determined by an expert panel. RESULTS: Questionnaires pertaining to 2,083 children were returned (participation rate of 74%). A moderate level of agreement was observed between parent and student questionnaire responses (r values = 0.36 to 0.50; P values < 0.001). The highest frequency of asthma-like symptoms was reported for African-American boys and the lowest for Caucasian girls. The items from the parent questionnaire that best predicted asthma were "breathing problems" (occurring rarely or more; odds ratio 12.8; 95% confidence interval, 4.5 to 36.1) and "problems coughing" (sometimes or more; odds ratio 9.7; 95% confidence interval, 3.6 to 26.5). Considering the presence of cough (sometimes or more) and/or breathing problem (rarely or more) yielded a sensitivity of 80%; a specificity of 75%, a positive predictive value of 50%, and a negative predictive value of 92%. Similar levels of prediction were observed for the items "trouble breathing" and "noisy breathing" as directly reported by the students. Allergic rhinitis was best predicted by report of a runny/stuffy no se (sometimes or more; sensitivity of 83%, specificity of 61%). Allergic conjunctivitis was best predicted by "itchy eyes." CONCLUSIONS: Administration of a school-based questionnaire is feasible, with a high response rate and excellent internal consistency. A high sensitivity and acceptable specificity was achieved by using one to two questions for asthma, allergic rhinitis, and allergic conjunctivitis. Among the children in grades 2 or above, comparable levels of prediction could be achieved with the student or parent version.

Adolescent↗
PubMed2003

Comparison of the efficacy of IGIV-C, 10% (caprylate/chromatography) and IGIV-SD, 10% as replacement therapy in primary immune deficiency. A randomized double-blind trial.

A novel method of large-scale chromatography has been developed to improve recovery and purity of immunoglobulin G (IgG) from pooled plasma. The current study compares safety, toxicity and efficacy of two intravenous immunoglobulin products: a novel formulation, IGIV caprylate/chromatography (IGIV-C; Gamunex, 10%) and a licensed solvent/detergent-treated product, Gamimune N, 10% (IGIV-SD). The study, a randomized, double-blind, parallel group, therapeutic equivalence trial, was conducted at 25 treatment centers in Canada and the United States. Patients (n=172) having confirmed chronic primary immunodeficiency (PID), aged 1-75 years, and receiving IGIV therapy were enrolled. For 9 months, patients were treated with IGIV-C or IGIV-SD in accordance with the patient's individualized treatment regimen utilized before study entry. The primary endpoint was the proportion of patients with >or=1 validated acute sinopulmonary infection during the treatment period. Secondary endpoints included the proportion of patients with all infections, time to first infection, annual infection rates, lung function parameters, infusion-related safety and viral safety. The annual validated infection rate in the IGIV-C group was 0.18 compared to 0.43 in the IGIV-SD group (p=0.023). Nine patients receiving IGIV-C experienced validated infections, compared to 17 patients in IGIV-SD group (p=0.06). Acute sinusitis (validated plus clinically defined) was less frequent in the IGIV-C group (p=0.012). Presence of bronchiectasis did not affect efficacy. Adverse reactions were similar in frequency and severity in both groups. No evidence of viral transmission was observed. IGIV-C appears to be superior to IGIV-SD in preventing validated sinopulmonary infections, especially acute sinusitis, in patients with PID.

Adolescent↗
PubMed2002

Prolonged inflammatory response to acute Pseudomonas challenge in interleukin-10 knockout mice.

Cystic fibrosis (CF) lung disease is characterized by a neutrophilic infiltrate that is excessive relative to the burden of infection. Decreased interleukin-10 in CF airways may impair proper termination of inflammation, leading to persistence of neutrophils after acute infections have been cleared. This could explain reports of lung inflammation in the absence of bacteria in infants with CF. We evaluated the kinetics of inflammation after transient Pseudomonas aeruginosa challenge in IL-10 knockout (KO) and wild-type (WT) mice. Both types of mice cleared the infection by Day 6 (p > or = 0.29). However, IL-10 KO mice had more neutrophils in bronchoalveolar lavage fluid than did WT mice on Days 4 (p < 0.0001), 6 (p < 0.0001), and 8 (p = 0.042). IL-10 KO mice had high concentrations of proinflammatory cytokines in BAL on Days 2 and 4, with some cytokines detectable on Days 6 and 8, whereas cytokines in BAL from WT mice were greatest on Day 2 and undetectable by Day 4. Moreover, IL-10 KO mice failed to regenerate IkappaBalpha once degraded and subsequently had prolonged activation of NF-kappaB. These data suggest that IL-10 deficiency contributes to prolonged inflammatory responses early in CF, when infection may be transient.

Acute Disease↗
PubMed2002

Functional IL-10 deficiency in the lung of cystic fibrosis (cftr(-/-)) and IL-10 knockout mice causes increased expression and function of B7 costimulatory molecules on alveolar macrophages.

Alveolar macrophages are poor APCs that only minimally express B7 costimulatory molecules. Because our previous data suggest that bronchial epithelial cells constitutively secrete IL-10, and IL-10 inhibits B7 expression in vitro, we hypothesized that this IL-10 is responsible for suppressing B7 expression on macrophages that enter the airways. Furthermore, because we have shown that cystic fibrosis (CF) lungs are deficient in IL-10, we hypothesized that bronchoalveolar macrophages (BALMs) from cystic fibrosis transmembrane conductance regulator (CFTR)(-/-) as well as IL-10(-/-) mice might express increased B7. Immunofluorescence for B7 was positive on BALMs from CF patients and CFTR(-/-) and IL-10(-/-) mice, but was negative on controls. FACS showed that 63.9% of BALMs from IL-10(-/-) mice were B7-1 positive, as were 67.4% of BALMs from CFTR(-/-) mice, whereas <7% of BALMs from wild-type controls were positive. Using BALMs to costimulate splenic T cells with anti-CD3 as a mitogen showed 9202 +/- 2107 cpm [(3)H]thymidine incorporation for BALMs from IL-10(-/-) mice and 4082 +/- 1036 cpm for BALMs from CFTR(-/-) mice, but <200 cpm with BALMs from either type of +/+ mouse. Treatment of CFTR(-/-) mice with recombinant mouse IL-10 reduced the B7 expression and costimulatory activity of the BALMs. These data suggest that the IL-10 secreted in the healthy lung may be responsible for the absence of B7 and poor costimulatory activity of BALMs and that reductions of pulmonary IL-10 in CF may enhance B7 expression and local immune responses.

Animals↗
PubMed2002

A history of immune globulin therapy, from the Harvard crash program to monoclonal antibodies.

Processes for the large-scale fractionation of human plasma using cold ethanol were initially developed by Edwin Cohn and his colleagues at Harvard to provide albumin as a treatment for shock in World War II. Procedures for further purification of gamma globulins and other proteins precipitating at lower concentrations of ethanol were then developed by Oncley et al. Gamma globulin rapidly replaced convalescent and animal sera for the prevention and treatment of infectious diseases such as measles, hepatitis, and polio, then came into widespread use as replacement therapy in the primary immune deficiencies, which emerged in the antibiotic era of the early 1950s. Although it took 40 years to develop preparations of gamma globulin that could be safely given intravenously, the eventual accomplishment of that goal has led to better treatment of antibody deficiency syndromes and also the wide use of high-dose intravenous immunoglobulin in autoimmune and inflammatory diseases. Those uses continue to expand even as monoclonal antibodies are being introduced for specific infectious diseases in high-risk populations.

Antibodies, Monoclonal↗
PubMed2002

Intravenous immunoglobulin: appropriate indications and uses in hematopoietic stem cell transplantation.

Intravenous immune globulin (IVIG) therapy has been prescribed in many different disease states. Hyperimmune products are also available. Recently, routine use for many indications has come under scrutiny secondary to high cost, limited supply, and unclear benefit. IVIG is U.S. Food and Drug Administration-approved for application in hematopoietic stem cell transplantation (HSCT), a very common indication for its use. In an attempt to clarify the most appropriate indications and doses in HSCT recipients, we conducted a MEDLINE search in which we reviewed all relevant articles from 1966 to the present. Search terms included bone marrow transplantation, intravenous immune globulin, hyperimmune globulin, GVHD, and cytomegalovirus (CMV). Also, the references of all pertinent studies and review articles were scanned for studies missed via MEDLINE. CMV prophylaxis/treatment and GVHD prophylaxis are the 2 indications with the most significant clinical support, but there are very few prospective, randomized, controlled trials reported. Furthermore, sample size usually was small, included heterogeneous patient populations, and employed different primary end points. Several reports support IVIG therapy in combination with ganciclovir for prevention and treatment of CMV infection, whereas others have shown ganciclovir monotherapy to be effective, blurring the benefit of IVIG administration. CMV IgG data are also imprecise and difficult to interpret. The role of IVIG therapy in prevention and treatment of GVHD also is vague. Only 1 randomized investigation showed a benefit in the prevention of acute GVHD, and no studies showed efficacy in chronic GVHD prophylaxis and therapy. Reports examining the utility of IVIG or CMV IgG in HSCT are hampered by marked variation in trial design and dosing and diverse patient characteristics. Although IVIG may be useful as a component of preemptive therapy and treatment of CMV disease, its contribution to the prevention of reactivation of CMV infection is dubious. Extended IVIG therapy during GVHD prevention may impair recovery of humoral immunity, and its role in prophylaxis and therapy of GVHD has not been clearly defined. Hospital monitoring programs may be a valuable way to detect areas of high use and allow for streamlining of prescribing.

Clinical Protocols↗
PubMed2002

The role of inflammation in the pathophysiology of CF lung disease.

Cystic fibrosis (CF) lung disease is characterized by a self-perpetuating cycle of airway obstruction, chronic bacterial infection, and vigorous inflammation that results in structural damage to the airway. CF patients have a predilection for infection with a limited spectrum of distinctive bacteria that initiate a vigorous inflammatory response which is more harmful than protective. The airway epithelial cell, which normally expresses the cystic fibrosis transmembrane conductance regulator (CFTR), directs the inflammatory response. Defects in CFTR are associated with increased production of pro-inflammatory mediators including IL-8, a potent neutrophil chemoattractant that stimulates the influx of massive numbers of neutrophils into the airways. These neutrophils are the primary effector cells responsible for the pathological manifestations of CF lung disease. Documented deficiencies in immunoregulatory molecules such as IL-10 likely contribute to the generation of the excessive and persistent inflammatory response. Since inflammation is a key contributor to the pathogenesis of CF lung disease, anti-inflammatory therapy must assume a larger role in CF until a cure is discovered. To date, attention has focused primarily on the therapeutic potential of systemic and inhaled corticosteroids and the non-steroidal anti-inflammatory drug (NSAID) ibuprofen. Development of new anti-inflammatory therapies that impact intracellular signaling pathways and cell-cell communication molecules likely will have the greatest impact on limiting the excessive production of the inflammatory mediators in the CF lung, thereby slowing the decline in lung function and improving survival.

Cystic Fibrosis↗
PubMedDate not supplied

Intravenous gamma-globulin therapy in bronchial asthma.

Two possible uses exist for intravenous gamma-globulin (IVIG) therapy in asthma. First, it has been suggested that high-dose IVIG can serve as an anti-inflammatory, immunomodulatory agent in steroid-dependent asthma patients. Second, IVIG can be used as a replacement treatment in those asthma patients with frank hypogammaglobulinemia or more subtle antibody deficiencies. The mechanisms by which IVIG functions are widely different in these two potential uses. Clear characterization of the patients' immune status is pivotal in choosing whether to use IVIG. The assessment should not be limited to simple determination of serum immunoglobulin A (IgA), IgG, IgM, and IgG subclass levels. When clinically warranted, the specific antibody response to active immunization with antigens such as those in Pneumovax may be invaluable in identifying patients with subtle antibody-deficiency disorders. Asthma in those patients may be improved markedly if infection is prevented by antibody-replacement therapy with IVIG.

Asthma↗
PubMedDate not supplied

Inflammatory mediators in cystic fibrosis lung disease.

Cystic fibrosis (CF) is a complex multisystem disorder caused by mutations in a membrane glycoprotein called the CF transmembrane regulator (CFTR), which has as its major function serving as a Cl- channel. The relationship between defects in CFTR and development of lung disease remains incompletely understood. Chronic lung disease, characterized by persistent infection with a peculiar type of Pseudomonas aeruginosa, bronchiectasis, and airway obstruction is the major cause of morbidity and mortality in CF patients. The inflammatory response to the chronic infection resembles that induced by lipopolysaccharide (LPS) and is mediated primarily by cytokines such as tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-6, and IL-8, whose synthesis is activated by the transcription factor nuclear factor kappa B (NF-kappa B). Large numbers of neutrophils dominate the inflammatory response and excessive concentrations of their products create a vicious cycle that becomes injurious rather than protective and eventually claims the life of the patient.

Cystic Fibrosis↗