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Biomedical subjects

J Paupe

Publications and source records attributed to J Paupe.

At least 19 recordsLinked to original sources
PubMed1995

IL-7 drives donor T cell proliferation and can costimulate cytokine secretion after MHC-matched allogeneic bone marrow transplantation.

Transplantation of MHC-matched, allogeneic B10.D2 bone marrow plus T cells into BALB/c recipients ultimately results in chronic graft-vs-host disease (GVHD) and mortality 8 to 12 wk post-transplant. We have identified IL-7-specific mRNA in the spleens of BALB/c bone marrow transplantation (BMT) recipients during the first week post-transplant. The response by T cells from B10.D2-->BALB/c BMT recipients to stimulation with IL-7 in vitro during the early period after transplant was then examined. The findings indicated that within the first week post-transplant, spleen cells removed from recipients injected with allogeneic, but not syngeneic, T cells proliferated vigorously to rIL-7. Both IL-2-dependent and -independent components were identified. Depletion of responding cells before culture with anti-Thy-1.2 Ab virtually eliminated this response. We conclude that transplant of allogeneic T cells is required for the observed IL-7 response, and moreover, such cells proliferate after exposure to this cytokine in vitro. To determine whether IL-7 could have a functional effect on donor T cells, the production of IFN-gamma by T cells from allogeneic BMT recipients stimulated with anti-T cell receptor (i.e., anti-V beta) Ab was examined. IL-7 was demonstrated to enhance IFN-gamma production by donor T cells postallogeneic BMT. These results suggest that a cytokine presumably produced in the host for the physiologic function of hematologic reconstitution is playing an additional role during the early events after allogeneic BMT mediated via the expansion and augmented cytokine production by donor T cells.

Animals↗
PubMed1994

Endogenous superantigens in allogeneic bone marrow transplant recipients rapidly and selectively expand donor T cells which can produce IFN-gamma.

Despite the existence of many non-MHC disparities between MHC matched but non-MHC mismatched donors and recipients, graft-versus-host disease (GVHD) is not clinically apparent following a significant number of allogeneic bone marrow transplants (BMT) in experimental animals. The present studies examined V beta TcR expression and IFN-gamma production by donor T cells in a BMT model involving an MHC matched, allogeneic donor-recipient combination which included a unidirectional superantigen disparity (Mls). B10.D2-->BALB/c, but not BALB/c-->B10.D2 recipients develop GVHD and mortality ensues 8-12 weeks post-transplant. During the first 2 weeks post-transplant of B10.D2-->BALB/c, approximately 50% of all Thy1.2+ spleen and lymph node cells were found to express T cell receptors utilizing V beta 3. A similar rapid and selective expansion of V beta 3+ TcR bearing donor T cells was detected in two other H-2 matched superantigen disparate donor-recipient BMT combinations. An increased percentage of V beta 3+ T cells was noted among both the CD4+ and CD8+ populations. Thus, in these donor/recipient combinations, all TcR families were not equally expanded early following transplant. At 4-10 days post-transplant, IFN-gamma specific mRNA was readily detected in the spleens of B10.D2-->BALB/cBMT recipients containing large numbers of V beta 3+ T cells. Moreover, V beta 3+ donor T cells from these recipients contained IFN-gamma mRNA. Specific stimulation in vitro with immobilized anti-TcR moAbs demonstrated that V beta 3+ T cells secreted a large amount of the total IFN-gamma levels detected. The ability of endogenous superantigens to activate large numbers of T cells which can produce cytokines after BMT indicates that when present, such antigenic differences may contribute to events occurring during initial graft-versus-host reactions. Such antigens could therefore participate in the events influencing whether GVHD develops following BMT between certain donors and recipients.

Animals↗
PubMed1992

[The asthmatic child].

Asthma is the most frequent chronic pediatric disease. Management is based on assessment of severity and should normalize lifestyle as well as pulmonary function. Mild asthma is treated with intermittent beta-2-agonists. Moderate asthma should receive non-steroids prophylactic anti-inflammatory drugs. Immunotherapy should be considered. Severe asthma requires inhaled steroids. At each stage inhaled medications should be preferred. Therefore inhalation delivery system must be adapted for children of different ages and degree of dyspnea. The importance of environment control is well recognized. Establishing a partnership with the child and its family and with the medical staff and with the child's school is always necessary.

Asthma↗
PubMed1992

Dissociation of symptom scores and bronchial hyperreactivity: study in asthmatic children on long-term treatment with inhaled beclomethasone dipropionate.

The aim of the study was to evaluate the effects of inhaled steroids (IS) on the improvement of clinical asthma symptoms and on the decrease in bronchial hyperreactivity (BHR). Twenty-four children with severe asthma were given 1,000 micrograms beclomethasone dipropionate (BDP) daily and compared with ten asthmatic control children. The study included the evaluation of daily clinical score, of exercise induced asthma, of bronchial obstruction (forced expiratory volume in 1 sec, FEV1), and of BHR at months 0, 1, 2-3, and 4-5 (M0, M1, M2-3, and M4-5). BHR was assessed by standardized inhaled carbachol provocation measuring plethysmographic specific airway resistance (SRaw). The carbachol dose causing a 40% decrease in specific conductance (SGaw) was determined (PD40 SGaw). Clinical scores decreased at M1 (P less than 0.01) and throughout the study. FEV1 increased at M1 (P less than 0.05), M2-3 (P less than 0.01), and M4-5 (P less than 0.05) compared to M0. PD40 SGaw only increased significantly at M1 and M2-3. No individual correlation was found between clinical scores and PD40 SGaw at any testing, or between the decrease of clinical scores and the decrease of BHR. We conclude that bronchoconstrictive challenge tests do not adequately assess the clinical efficacy of IS. In clinical practice non-specific BHR should be preferentially measured for diagnosing atypical forms of asthma.

Administration, Inhalation↗
PubMed1992

Modifications in tissue histamine levels in mice treated with chronic epicutaneous application of phorbol-12-myristate-13-acetate.

Chronic epicutaneous application of phorbol-12-myristate-13-acetate (PMA) on the right flank of C 57 BL/6 mice induces an inflammatory reaction and a selective increase in skin histamine level at the site of treatment. Tissue histamine levels were not increased at other sites such as contralateral skin, stomach rumen and skeletal muscle, and were decreased in stomach fundus and dorsal skin. These results are in agreement with the hypothesis that mast cells play a significant role in cutaneous inflammation induced by PMA.

Administration, Cutaneous↗
PubMed1992

Clinical trials on pediatric lower-respiratory-tract infection: results and comments with cefetamet pivoxil.

A total of 30 pediatric patients suffering from lower-respiratory-tract infections were admitted to a three-arm, open, randomized study comparing two different doses of cefetamet pivoxil (either 10 or 20 mg/kg b.i.d.; groups A and B, respectively) with the standard cefaclor treatment (10 mg/kg t.i.d.; group C) for 7-12 days. The 30 cases were randomly assigned to the three treatment arms which were comparable with regard to demographics as well as to diagnosis on admission and concomitant medication. The children ranged from 1.08 to 12 years in age, and comprised 18 males and 12 females, with a weight range of 11-42 kg. As is to be expected in these patients, bacteriology was mostly not assessable. The overall clinical outcome was cure in 9, 8 and 9 cases, respectively, and improvement in 1, 2 and 0 cases, respectively. In the cefaclor group 1 patient failed to respond. Signs and symptoms of disease improved significantly in the three treatment groups; there were no intergroup differences. Vital signs (morning and evening temperature and pulse rate) improved in parallel. Radiological results had improved by the end of treatment in 9/10 patients in group A, in 10/10 patients in group B, and in 9/10 evaluable patients in group C. Mild to moderate nausea or vomiting were each reported in 1 patient in group A. Platelet increase was reported as a mild adverse event in 2 patients in each of the cefetamet pivoxil groups and in 4 patients given cefaclor.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗
PubMed1991

Immunotherapy with an oral bacterial extract (OM-85 BV) for upper respiratory infections.

The efficacy of Broncho-Vaxom/Imocur (OM-85 BV), an orally administered lyophilized bacterial extract, for recurrent respiratory and ear, nose and throat (ENT) infections was evaluated in 116 children aged 6 months to 19 years by comparing its activity in 61 children with that of a placebo in 55 children. The study was randomized, double-blind, and comprised a 90-day treatment period followed by a 90-day follow-up period without test drugs. Over the 180 days, 39.5% of patients taking OM-85 BV remained free from infection compared with 16.5% on placebo (p less than 0.01). 44% on OM-85 BV did not need antibiotics compared with 23.5% on placebo (p less than 0.05). These differences were even greater in the subgroup of children aged 6 years and less (34 vs. 3.5% for the absence of infections, p less than 0.01 and 37 vs. 10% for the need of antibiotics, p less than 0.05). Tolerance to OM-85 BV was excellent, and laboratory investigations showed no abnormalities attributable to this product. This work confirms that the immunomodulator OM-85 BV is an effective immunotherapy for recurrent respiratory and ENT infections in children.

Adjuvants, Immunologic↗
PubMed1991

[Mucoviscidosis and allergic bronchopulmonary aspergillosis].

Allergic bronchopulmonary aspergillosis (ABPA) is a severe disease inducing bronchopulmonary anatomic lesions which complicate those already present in patients with cystic fibrosis. The frequency of this association is estimated between 0.6 and 10% according to American studies. Diagnosis of ABPA is difficult, as findings such as sibilant rales, pulmonary infiltrates, bronchiectasies, anti-aspergillus precipitins may be present as single features in patients with cystic fibrosis. Thus it is important to ascertain the diagnosis as oral corticosteroid treatment is the only one able to prevent evolution towards bronchiectasies and pulmonary fibrosis.

Adolescent↗
PubMed1990

Scavengers of free radical oxygen affect the generation of low molecular weight DNA in stimulated lymphocytes from patients with systemic lupus erythematosus.

Factors that potentially affect the generation of excess low molecular weight DNA (LMW-DNA) in cultured phytohemagglutinin (PHA)-stimulated lymphocytes of patients with systemic lupus erythematosus (SLE) were studied because this species of DNA is consistently found and this DNA may play a role in the pathogenesis of the disease. Superoxide dismutase (SOD; 0.05 mg/mL), a scavenger of free radical oxygen, decrease LMW-DNA formation in lymphocytes by 22%. Co-cultivation with cysteamine, a second scavenger of free radical oxygen and a sulfhydryl radioprotective agent, resulted in a 32% decrease in the generation of excess LMW-DNA at a concentration of 0.5 x 10(-3) mol/L and largely prevented its formation at 1.0 x 10(-3) mol/L. Other free radical scavengers (catalase, mannitol, vitamins C and E), cyclooxygenase inhibitors (ibuprofen and aspirin), a xanthine oxidase inhibitor (allopurinol), and an iron chelator (desferoxamine) did not affect excess LMW-DNA formation. Glutathione (1 x 10(-3) mol/L) had no effect and cysteine was toxic. Because scavengers of free radicals might be useful in the therapy of lupus, a trial of cysteamine (30 to 60 mg/kg/d) was administered to six acutely ill patients with SLE. A therapeutic benefit was not demonstrated, and some patients had exacerbation of disease. Lymphocyte cell growth from control and lupus subjects was stimulated when cysteamine, 1 x 10(-5) to 1 x 10(-4) mol/L was added to the media, but inhibited at concentrations of 2 x 10(-4) mol/L or greater. These studies suggest that the autooxidation and toxicity of high-dose cysteamine preclude its therapeutic use as a free radical scavenger.

Adult↗
PubMed1990

[Accelerated desensitization with Dermatophagoides pteronyssinus in severe asthmatic children. Evaluation after one year of immunotherapy].

An homogeneous group of 17 children with severe chronic asthma were given a rush immunotherapy with standardized Dermatophagoides pteronyssinus extracts. Maintenance dose was injected monthly for one year. Symptom and medication scores as well as functional (lung function tests, specific nasal challenges), immunologic and allergic parameters (skin tests, total serum IgE, specific IgE and IgG4) were recorded before and at the end of the study. Rush immunotherapy was well tolerated in spite of some moderate systemic adverse reactions. Symptom and medication scores improved in 10 children. Nasal and skin sensitivity decreased in respectively 3 and 7 children. However there was no correlation between the improvement of quality of life and laboratory results. This study shows that specific immunotherapy is possible in children with severe asthma. Its efficacy should be assessed by symptom and medication scores.

Acari↗
PubMed1990

[Diagnostic approach of pleural effusion in children. Report of 59 cases].

The retrospective analysis of 59 pediatric cases of pleural effusion showed that infectious agents account for 80% of cases. Thoracentesis proved to be the first-line diagnostic tool. Pleural biopsy was diagnostic in four tuberculous and two malignant pleural effusions. The literature data shows that pleural fluid total protein, lactate deshydrogenase, glucose, pH, white blood cell count and differential should be obtained in all patients. Because of the high incidence of infection, microbiologic studies are also indicated in children. These studies are of great value in distinguishing transudates from exsudates and in deciding on pleural drainage.

Adolescent↗
PubMed1990

[Practical diagnostic approach to anomalies of the aortic arch. Apropos of 31 pediatric cases].

This analysis of 31 cases of anomalies of the aortic arch has confirmed the predominance of subclavian retro-oesophageal arteries and double aortic arches (74% of cases). The age at which the first clinical signs presented was less than one year in 75% of cases. Respiratory signs predominated with recurrent bronchitis (16 cases) and bronchial congestion (9 cases). These signs were not specific for the type of aetiology and were characterised by their chronicity and recurrent nature. Inspiratory and expiratory stridor was found on 8 occasions and was very suggestive of the diagnosis. There was a frequent association of asthma and anomalies of the aortic arch in this series (13 cases) with 6 cases of atopic asthma in early childhood and 7 cases of asthma in infancy. The oesophago-gastroduodenal transit was the key diagnosis which enabled the vascular anomaly to be confirmed. There was, however, a failure on 5 occasions with 2 false negatives and 3 cases where the wrong type was suspected. Fibreoptic bronchoscopy enabled the topography to be established more precisely including the degree of compression (in 14 cases) and showed evidence of associated tracheomalacia in 7 cases. Nuclear magnetic resonance was very helpful, giving a better definition of the anatomical type and of the relationship of the vascular arch with the oesophago-tracheal axis. Broncho-fibroscopy and nuclear magnetic resonance make strong contributions towards the indications for operation.

Adolescent↗
PubMed1990

[Value of Imocur in the prevention of recurrent infections in children under six years of age. Results of a multicenter, placebo-controlled trial].

Sixty-four children under six years of age with recurrent ear, nose and throat and/or lower respiratory tract infections (three episodes or more during the previous winter) were included in a double-blind, placebo-controlled study of the oral bacterial immunomodulator Imocur. Imocur provided better individual protection than the placebo throughout the three-month treatment period and the subsequent three-month follow-up period. Among the patients given Imocur, 34% remained free of infection and 37% required no antimicrobial drugs throughout the six-month study period, as compared with 3% and 10%, respectively, among the controls. The number of infectious episodes per patients during the six-month study period was 4.86 among controls versus 1.66 among patients given Imocur. Use of antimicrobial agents was reduced by half among patients treated with Imocur as compared with controls. Tolerance was outstanding, with no adverse effects among treated patients. These results show that Imocur is an effective immunomodulator for the treatment of recurrent ear, nose and throat and/or lower respiratory tract infections in children.

Adjuvants, Immunologic↗
PubMed1990

[Consensus conference. The management of asthma in children].

At this international consensus conference, a number of conclusions concerning the diagnosis and management of childhood asthma were reached. The following practical definition was given to asthma: intermittent wheezing and/or cough in a clinical situation where asthma is likely and less common diseases have been outruled. A thorough clinical history is essential to the diagnosis of asthma. Additional tests are used only to confirm the clinical impression and to provide objective evidence supporting therapeutic recommendations. Multidisciplinary management includes an evaluation of psychosocial factors and patient information. Drugs should be selected according to the severity of the condition: beta-2-agonists for intermittent mild wheezing; cromolyn sodium for moderate to severe asthma; xanthines, ipratropium bromide, and oral corticosteroids in more persistent and severe forms. The child and parents should be told that a normal, physically active life is quite possible if the disease is correctly controlled. The reward for correct management of asthma is resumption, in nearly every case, of a normal life including active participation in sports.

Adolescent↗
PubMed1989

Hymenoptera venom immunotherapy. I. Induction of T cell-mediated immunity by honeybee venom immunotherapy: relationships with specific antibody responses.

The specific cell-mediated and humoral immune responses of 14 children allergic to honeybee venom were studied. An 8-day rush venom immunotherapy induced an increase in T proliferative (p less than 0.04) and T suppressive (p less than 0.003) cell-specific activities. Antibody variations, an increase in specific IgG4 (p not equal to 0.05), and a decrease in specific IgE (p less than 0.01) were observed 1 year later. Initial high T suppressive cell activity prevents T proliferative cell increase during rush venom immunotherapy. High initial levels of specific IgG1 and specific IgG4 have opposing effects on the increase in T suppressive cell activity, the former being positively correlated with intensive increase (r = 0.840; p less than 0.005), the latter negatively with T suppressive cell increase (r = -0.709; p less than 0.001). These data indicate that there are interrelationships between the cell-mediated immunity and the antibody responses in honeybee allergy.

Adolescent↗