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T Pressler

Publications and source records attributed to T Pressler.

34 records · Page 2Linked to original sources
PubMed1990

IgG subclass antibodies to Pseudomonas aeruginosa in sera from patients with chronic Ps. aeruginosa infection investigated by ELISA.

ELISAs using subclass-specific monoclonal antibodies were developed for the quantification of human IgG1, IgG2, IgG3 and IgG4 antibodies to Ps. aeruginosa. We investigated the pattern of IgG subclass antibodies against Ps. aeruginosa in serum from patients with cystic fibrosis (CF), other patients with chronic Ps. aeruginosa infection, and healthy controls. Healthy controls and patients with CF but without Ps. aeruginosa infection showed no or very low titres of antibodies against Ps. aeruginosa. In the early stage of chronic Ps. aeruginosa infection, antibody titres in all four subclasses were significantly higher than either normals or CF patients without infection. Other patients with Ps. aeruginosa infection showed the same increased level of IgG subclass antibodies as CF patients in an early stage of infection. Sixteen patients (eight in good and eight in poor clinical condition) have been followed for an average of 13 years with multiple serum samples covering the pre-infection, early and late stages of chronic infection. Patients in a poor clinical condition showed significantly higher levels of IgG3 antibodies in the first year of infection and 2 years later also had significantly higher IgG2 antibody levels. We conclude that elevated levels of IgG2 and IgG3 antibodies to Ps. aeruginosa are a sign of poor prognosis in CF.

Adolescent↗
PubMed1990

Immunology of Pseudomonas aeruginosa infection in cystic fibrosis.

Adherence of P. aeruginosa to the lining of the respiratory tract is probably mediated by interaction of pili or alginate with lactosyl and sialosyl residues on the respiratory cells. The toxins produced by P. aeruginosa (for example, elastase and alkaline protease) may play a key role during the initial persistent colonization as they interfere with important defense mechanisms. Neutralizing antibodies are eventually produced, and a poor prognosis is correlated to a pronounced antibody response. The bacteria are protected against the host's defense mechanisms by production of alginate which encapsulates microcolonies of P. aeruginosa in the lungs. During the chronic infection, toxins of P. aeruginosa probably play little if any direct pathogenic role, however, immune complexes seem to be a major trigger of chronic inflammation in the lungs. Proteolytic enzymes and oxygen radicals released from the abundance of neutrophils in the lungs are probably responsible for most of the tissue damage. The individual course of the chronic infection may be explained by regulatory mechanisms, such as cleavage of immune complexes by neutrophil elastase, and by the balance between the different IgG subclass-specific antibody responses.

Bacterial Adhesion↗
PubMed1989

Antilipopolysaccharide antibodies and differential diagnosis of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis.

Chronic lung infection in cystic fibrosis is characteristically associated with polyagglutinable, serum-sensitive, mucoid strains of Pseudomonas aeruginosa. Enzyme-linked immunosorbent assay (ELISA) methods for standard-free quantitation of immunoglobulin G (IgG) and IgM antibodies to P. aeruginosa lipopolysaccharides (LPSs) have been developed. We now report the development of assays for quantitation of monomer and dimer total IgA and IgA anti-LPS antibodies. Use of these methods in diagnosis of early chronic P. aeruginosa lung infection was assessed. IgG and IgA anti-LPS levels increased significantly at the onset of chronic infection and continued to increase to very high levels in the later stages of infection. IgM anti-LPS levels also rose at the onset of chronic infection but did not increase further. The function of true- and false-positive rates was illustrated by using various concentrations of IgG, IgA, and IgM anti-LPS for discrimination of patients. Values that gave optimum separations were used for statistical evaluation of the diagnostic sensitivities and specificities of anti-LPS antibody concentrations. The results obtained in these assays were compared with a diagnosis, based on the number of precipitins in crossed immunoelectrophoresis, of serum samples from cystic fibrosis patients. In 64 paired serum samples taken before and immediately after the onset of chronic infection, as defined by crossed immunoelectrophoresis precipitins, the predictive values of a positive ELISA were 86% for IgG and 89% for IgA. The predictive values for a negative ELISA were 98% for IgG and 97% for IgA. Results of the IgM anti-LPS ELISA had a lower predictive value. Immunoblotting and absorption studies showed that IgG anti-LPS antibodies were directed specifically against LPS of P. aeuruginosa. ELISAs were developed to determine the specific IgG sublclasses involved. The increase in IgG anti-LPS involved all four subclasses. Highest anti-LPS titers were seen with IgG1 and IgG4, but the largest relative increases were seen with IgG2 and IgG3.

Antibodies, Bacterial↗
PubMed1988

Increased IgG2 and IgG3 concentration is associated with advanced Pseudomonas aeruginosa infection and poor pulmonary function in cystic fibrosis.

The concentrations of IgG subclass immunoglobulins were determined by radial immunodiffusion in serum from 126 patients with cystic fibrosis (CF). The results were compared to values from age-matched healthy children and adults and correlated to patients age, duration of chronic Pseudomonas aeruginosa infection and lung function parameters. Fifty-two percent of the patients had an elevated concentration of at least one of the IgG subclasses; IgG1 28%, IgG2 16%, IgG3 18% and IgG4 48%. There was significant correlation between elevated serum levels of IgG2, and to a lesser extent IgG3, with decreased lung function (for FEV1; p = 0.0001, and p = 0.001 respectively) and high levels of antipseudomonas precipitins (p = 0.008, and p = 0.002). A similar correlation was not found for IgG1 and IgG4. IgG subclasses vary in their ability to promote phagocytosis and to activate complement and it is possible that individual differences in the IgG subclass pattern could explain the variable course of this disease.

Adolescent↗
PubMed1987

Acute promyelocytic leukemia with t(15;17) and t(2;17;15).

Cytogenetic examination in a case of acute promyelocytic leukemia (FAB-M3) demonstrated a stem line with t(15;17) and a side line with t(2;17;15). This observation indicates either clonal evolution from the standard translocation or a de novo complicated translocation. Previous cases with three-way translocations in acute promyelocytic leukemia have been reviewed. Three-way translocations seem to occur with similar frequency in M2 and M3 types of acute myeloid leukemia and in chronic myelocytic leukemia.

Child↗
PubMed1987

Combined imipenem/cilastatin and tobramycin therapy of multiresistant Pseudomonas aeruginosa in cystic fibrosis.

Ten patients with cystic fibrosis (CF) and chronic broncho-pulmonary Pseudomonas aeruginosa infection were given imipenem/cilastatin (100 mg/kg/day) in combination with tobramycin (15 mg/kg/day). Forced vital capacity and forced expiratory volume in the first second improved significantly in nine out of ten patients, and most of the patients improved clinically. P. aeruginosa was not eradicated in any patient and resistance against imipenem developed in all patients during treatment. A concomitant increase in MIC of piperacillin and ceftazidime occurred during treatment. In-vitro bactericidal synergy of imipenem and tobramycin was noted in 57% of pretreatment isolates. Seven patients complained of adverse reactions, mainly gastrointestinal, and treatment of three patients was discontinued after 5, 8, and 12 days of therapy, because of rash or nausea and vomiting. The side effects were considered to be due to imipenem/cilastatin. Because of the rapid development of imipenem resistance despite combination therapy, the high proportion of side effects, and the risk of induction of beta-lactam resistance, imipenem/cilastatin cannot be recommended for routine treatment of CF-patients with P. aeruginosa infection.

Adolescent↗
PubMed1986

Pharmacokinetics of erythrocyte methotrexate in children with acute lymphoblastic leukemia during maintenance treatment.

The concentration of methotrexate (MTX) in erythrocytes (E-MTX) was measured in 47 children with acute lymphoblastic leukemia during maintenance treatment with MTX 1.7-21.6 mg/m2/week and 6-mercaptopurine 25-75 mg/m2/day. At the time of measurement the plasma MTX concentration was less than 2 nmol/l. The steady state E-MTX varied between 51 and 202 nmol/l erythrocytes. Alterations in the E-MTX took place over 8-12 weeks after a change in dosage. A significant correlation was found between the E-MTX and the weekly dose of MTX administered. Noncompliance was revealed in two patients. A very low E-MTX was found in one patients, probably caused by inhibition of erythropoiesis. No correlation was found between E-MTX and the total amount of MTX administered or the length of treatment. A terminal half-life of 2-5 weeks after discontinuation of the drug showed that the erythrocytes functioned as a slow-changing compartment for MTX. Unexpectedly low E-MTX could mean noncompliance, impaired erythropoiesis, altered metabolism, or poor drug absorption.

Absorption↗
PubMed1986

Sultamicillin--a new antibiotic in the treatment of persistent lower respiratory tract infections caused by Haemophilus influenzae.

Haemophilus influenzae is a frequent cause of recurrent or chronic lower respiratory tract infections in patients suffering from cystic fibrosis (CF) and other chronic obstructive pulmonary disease (COPD). Ampicillin and its derivatives are routinely used in treatment, but resistant strains producing beta-lactamase frequently necessitate the use of other antibiotics. Sultamicillin is a compound agent for oral use in which ampicillin and the beta-lactamase inhibitor sulbactam are linked as a double ester. This combination is active in vitro against many beta-lactamase producing bacteria including ampicillin-resistant H. influenzae. Eight CF children and ten children with other COPD suffering from chronic or recurrent H. influenzae infection of the lower respiratory tract were treated with sultamicillin orally, 25 mg/kg, 12-hourly, for two weeks. Nine infections were caused by ampicillin-resistant strains. At the end of the treatment 65% of the patients were free of H. influenzae. The only adverse reaction was diarrhoea which occurred in 14 patients, and necessitated withdrawal of one patient from the study.

Adolescent↗
PubMed1986

Does centralized treatment of cystic fibrosis increase the risk of Pseudomonas aeruginosa infection?

Two hundred and forty Danish patients with cystic fibrosis (97% of the total CF population in Denmark) participated in a point-prevalence study of Pseudomonas aeruginosa infection. One hundred and ninety-two patients were treated at the Danish CF centre and 48 patients were treated in other places. The age distribution was significantly different as no patients older than 19 years were found in the non-centre group. Pathogenic bacteria were isolated from the sputum of 96% of the patients. P. aeruginosa was more prevalent in patients from the centre, whereas Staphylococcus aureus was more prevalent in the non-centre group. No difference in serogroup and phage pattern of P. aeruginosa was found. There was a tendency that non-centre treated patients acquired chronic broncho-pulmonary P. aeruginosa infection later, but at the age of 16 years 90% of all patients will be chronically infected. Chronic P. aeruginosa infection was significantly more common in the age group 10-14 years at the centre than outside the centre. It is not possible to prevent chronic P. aeruginosa infection in CF patients treated in small groups and because of the better prognosis of centralized treatment the latter must be recommended.

Adolescent↗
PubMed1986

Immediate and prolonged clinical efficacy of ceftazidime versus ceftazidime plus tobramycin in chronic Pseudomonas aeruginosa infection in cystic fibrosis.

20 patients with cystic fibrosis and chronic bronchopulmonary infection due to Pseudomonas aeruginosa entered a randomized cross-over study comparing ceftazidime (150 mg/kg body weight/24 h) plus tobramycin (10 mg/kg body weight/24 h) to ceftazidime alone (150 mg/kg body weight/24 h), both given intravenously for 2 weeks. 17 patients completed the study; both treatment regimens improved lung function and decreased the WBC count. No difference in clinical efficacy was found between the treatments. Pulmonary function returned to pre-treatment levels 3 months later with no difference between the treatments. No changes were seen in minimal inhibitory concentrations during treatment. None of the patients developed hypersensitivity or experienced serious adverse reactions to the drugs.

Adult↗
PubMed1986

Folic acid supplements in vitamin tablets: a determinant of hematological drug tolerance in maintenance therapy of childhood acute lymphoblastic leukemia.

Methotrexate (MTX) is an antifolate that inhibits cell division by reducing intracellular amounts of reduced tetrahydrofolates. Of 53 children with acute lymphoblastic leukemia (ALL) in maintenance treatment with MTX and 6-mercaptopurine (6-MP), 25 had received daily folic acid supplements in vitamin tablets containing 75-200 micrograms folic acid for at least the preceding 3-month period. Experimental data have shown that increased folate concentrations intracellularly inhibit MTX metabolism and toxicity. Therefore we found it relevant to investigate the extent to which folic acid supplements affect hematological tolerance to MTX and 6-MP in children during maintenance therapy for ALL. The erythrocyte folate (ery-folate) concentration was significantly higher in children who received extra folic acid than in those who did not (p less than 0.001). The ery-folate in MTX-treated children was only marginally reduced compared with the controls. The erythrocyte methotrexate (ery-MTX) concentration correlated with the weekly dose of MTX but not with any of the investigated hematological parameters. Children who received vitamin tablets containing folic acid had higher thrombocyte counts (p = 0.0056), higher leukocyte counts (p = 0.06), higher neutrophil counts (p = 0.05), and lower erythrocyte mean cell volumes (p = 0.05) than children who received no folic acid. We conclude that folic acid supplements of 75-200 micrograms/day affect the proliferative capacity of the bone marrow. Since none of the children was folate deficient as judged by the ery-folate, we recommend that vitamins given to children in maintenance treatment with MTX and 6-MP for ALL should not contain folic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Imipenem/cilastatin treatment of multiresistant Pseudomonas aeruginosa lung infection in cystic fibrosis.

Ten patients with cystic fibrosis and chronic broncho-pulmonary Pseudomonas aeruginosa infection received 45 mg imipenem/cilastatin per kg body weight/day, intravenously for two weeks. The treatment was safe with only minor side effects and clinical parameters improved considerably during therapy. In all patients resistance of Ps. aeruginosa to imipenem developed in the second week of treatment; in seven patients the therapy selected for a resistant strain and in three resistance developed in the original strain. The resistance persisted after cessation of treatment and thus the clinical usefulness of imipenem/cilastatin as monotherapy in CF-patients with Ps. aeruginosa seems to be limited.

Adolescent↗
PubMed1984

Antibiotic treatment of Haemophilus influenzae and Haemophilus parainfluenzae infections in patients with cystic fibrosis.

During the period 1977-81, 188 Cystic fibrosis patients have been treated with 1 254 anti-haemophilus treatments in the Danish Cystic Fibrosis Center. On an average, each patient received 1.7 courses of chemotherapy per year. Haemophilus infections were more prevalent in the youngest age group of patients. The average number of H. influenzae precipitins increased with age, and this pattern was consistent throughout the whole study. The standard treatment was orally administered pivampicillin or amoxicillin given for 14 days. 1 case of allergy or ampicillin-resistant strains, erythromycin was given, in most cases alone, in some cases in combination with rifampicin. The overall results showed, that H. influenzae was eradicated from sputum by a single course of chemotherapy in 73% of the courses and H. parainfluenzae in 100% of the courses. Six per cent of the patients suffered from chronic H. influenzae infection in spite of repeated treatments. No decrease of treatment efficiency was found even after many repeated chemotherapy courses. The prevalence of patients harbouring ampicillin-resistant H. influenzae increased in the beginning of the period (6%-20%), but a slight fall was subsequently observed.

Adolescent↗
PubMedDate not supplied

Specific IgG2 antibodies to Pseudomonas aeruginosa lipid A and lipopolysaccharide are early markers of chronic infection in patients with cystic fibrosis.

The IgG subclass antibody response to the two parts of Pseudomonas aeruginosa lipopolysaccharide; endotoxic lipid A and the O-polysaccharide, were investigated in a retrospective longitudinal study involving 16 patients with cystic fibrosis and chronic P. aeruginosa lung infection. The purpose of the study was to see if any of the IgG subclasses of either specificity could be used as prognostic markers in the development and subsequent course of the lung disease. IgG2 anti-lipid A, IgG3 anti-lipid A, and IgG2 anti-polysaccharide showed a significant positive correlation with deteriorating pulmonary function already before chronic P. aeruginosa lung infection was diagnosed as well as in subsequent years. The findings suggest antigenic exposure of the patient before chronic infection is detected by routine sputum examinations, and further support our previous findings of a critical role of the IgG subclass response in modulating the course of inflammatory lung damage in these patients.

Adolescent↗
PubMedDate not supplied

Pharmacokinetic evaluation of imipenem combined with cilastatin in cystic fibrosis.

The pharmacokinetics of imipenem (MK-787) and cilastatin (MK-791) were studied in 30 patients with cystic fibrosis (CF) receiving the drug for therapeutic purposes at doses of 11 mg/kg given as a 30-min infusion. The serum concentrations and urine elimination were studied after the first dose and during steady state. The concentrations were assayed by high-pressure liquid chromatography. The total areas under the imipenem serum concentration curves (AUCs) to infinity were 30.4 +/- 6.8 mg.h/l after the first dose compared with 29.1 +/- 7.1 mg.h/l during steady state (NS). The cilastatin AUCs on the 2 days were 40.3 +/- 9.3 and 38.3 +/- 0.4 mg.h/l (NS), respectively. The urinary recovery of imipenem was 47.8 +/- 17.8% after the first dose and 57.8 +/- 24.2% during steady state (NS). The amounts of cilastatin eliminated in the urine during 6 h were 6/7.3 +/- 22.9% after the first dose and 60.5 +/- 17.0% of the dose during steady state (NS). The mean half-life of imipenem in these CF patients was 1.2 +/- 0.4 h on the first day of the examination and within the same range during steady state. The distribution volume (Vd beta) was in the range of 28 liters, the total body clearance was 16.3 liters/h (285 ml/min) on the first day. The t1/2 of cilastatin was 0.59 +/- 0.14 h after the first dose and 0.61 +/- 0.14 h during steady state. Thus patients with CF eliminated cilastatin more quickly than imipenem.

Adolescent↗