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Biomedical subjects

F Zepp

Publications and source records attributed to F Zepp.

At least 19 recordsLinked to original sources
PubMed1997

Evidence for induction of polysaccharide specific B-cell-memory in the 1st year of life: plain Haemophilus influenzae type b-PRP (Hib) boosters children primed with a tetanus-conjugate Hib-DTPa-HBV combined vaccine.

UNLABELLED: The lack of an adequate immune response to the major polysaccharide of the Haemophilus influenzae type b (Hib) capsule (polyribosyl ribitol phosphate) (PRP) in very young infants (< 18 months) can be overcome by conjugating PRP to a T-cell dependent carrier protein. We studied whether administration of a tetanus-PRP conjugate vaccine reconstituted with a diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine as a three dose primary course at 3, 4 and 5 months of age induced PRP-specific immunological memory, by examining the anti-PRP response to a dose of unconjugated PRP given with the DTPa-HBV booster approximately 1 year later. The unconjugated PRP elicited protective anti-PRP antibody levels (> or = 0.15 microgram/ml) in all but 3 of the 369 vaccinees, including 13 infants who failed to demonstrate a measurable immune response after the primary course. In a sub-cohort of 54 subjects all had anti-PRP levels > or = 0.5 microgram/ml within 7-14 days of the booster showing a rapid anamnestic type response. Both primary and booster responses were predominantly IgGl indicating a T-cell dependent response. The DTPa-HBV components elicited protective anti-diphtheria, anti-tetanus and anti-HBs antibody levels in > or = 98.5% of vaccinees, and immune responses to each of the acellular pertussis vaccine components in 92.3%-97.3% of subjects. CONCLUSION: The tetanus-PRP conjugate vaccine not only elicited a good primary humoral response, but also induced immunological memory so that the infants were able to mount a large and rapid immune response to subsequent exposure to plain PRP, indicating that protection against circulating wild-type Hib had been generated. Successful induction of immunological memory occurred even when there was no measurable humoral anti-PRP response to the primary course. Tetanus-PRP conjugate vaccine can be used in combination with DTPa-HBV vaccine, when administered separately or as a single injection in the same syringe, in primary immunisation schedules at 3, 4 and 5 months of age.

Age Factors↗
PubMed1997

Predictability of early atopy by cord blood-IgE and parental history.

BACKGROUND: Atopic family history and cord blood IgE have been used as predictors of atopic disease in newborns for about 20 years, but at least for cord blood IgE the sensitivity has been shown to be very low. The objective of this paper was to evaluate whether parental history and cord blood-IgE were more accurate predictors for the appropriate atopic phenotypes in the infants rather than for any atopy. METHODS: A total of 1314 newborn infants was recruited in six German obstetric departments in 1990 and followed-up for 2 years. Four hundred and ninety-nine (38%) were at high risk for atopy with at least two first degree atopic family members and/or elevated cord-blood IgE concentrations. RESULTS: The cumulative incidence of atopic dermatitis over the first 2 years of life (AD24) amounted to 20.1%, and there was a significant association with AD history of the mother (OR 2.5, 95%CI 1.46-4.26) and of the father (OR 3.53, 95%CI 1.90-6.54). The cumulative incidence of recurrent wheezing in the first 2 years of life (RW24) amounted to 16.1%, and was positively associated with asthma history (OR 2.11, 95%CI 1.33-3.60) and sensitization history (OR 1.64, 95%CI 1.34-2.36) of the mother, but with neither for the father. RW24 was less prevalent in girls than in boys (OR 0.64, 95%CI 0.47-0.89). Thirty-one per cent of infants were sensitized (CAP test value > 0.35 kU/L) against at least one of nine food or inhalative allergens (S24) and this was significantly associated with cord blood-IgE value (OR 2.43, 95%CI 1.69-3.49), and sensitization history of the mother (OR 1.64, 95%CI 1.18-2.41). Using multiple logistic regression analysis, the prediction of AD24 by AD of parents, of RW24 by asthma of parents, and of sensitization by cord blood IgE was of low accuracy. CONCLUSION: The predictive capacity of parental history and cord blood IgE is not high enough to recommend them as screening instruments for primary prevention. The majority of atopic manifestations and of sensitization occur in infants with no demonstrable risk at birth.

Adult↗
PubMed1997

Cell-mediated immunity after pertussis vaccination and after natural infection.

The aim of this study was the investigation of the specific cell-mediated (CMI) responses induced by DTaP and to compare these data to immunity after natural infection. The ability of peripheral blood T-lymphocytes to respond to the pertussis related antigens pertussis-toxin (PT), filamentous haemagglutinin (FHA), and Pertactin (PRN) was investigated in 40 children before vaccination and at different times after vaccination with DTaP (Infanrix) by measurement of antigen-specific proliferation, lymphocyte phenotype, cytokine production and expression of activation markers (CD25, HLADR). Similar investigations were performed in children 4-6 weeks after recovery from natural pertussis. DTaP created a specific T-cell-response to PT, FHA and PRN that increased continually, depending on the progress of the vaccination schedule. In contrast to waning antibody titres, CMI was stable even between the post-basic vaccination and the pre-booster period. The magnitude of CMI after DTaP equalled those after natural infection. Measurement of cytokine-pattern showed induction of IFN-tau-producing T-helper-1-cells with lower stimulation of IL 10-producing T-helper-2-cells for DTaP and natural infection. Our data indicate that DTaP-vaccination induces a potent immune response to PT, FHA, and PRN at least equivalent to CMI after natural infection. The finding of a preferential T-helper-1-induction after DTaP and natural infection suggests a role of IFN gamma-activated macrophages in the protective response against B. pertussis-induced disease.

Adhesins, Bacterial↗
PubMed1997

Safety and efficacy of acellular pertussis vaccines: the Mainz study and other recent studies.

Following concerns about the safety and reactogenicity profile of diphtheria, tetanus and whole cell pertussis vaccines (DTwP), new and less reactogenic alternatives were developed over the last two decades. The new diphtheria, tetanus and acellular pertussis vaccines (DTaP) no longer consist of the whole bacterial cell but of either extracts or of a few highly purified components. While it soon became clear that DTaP vaccines are significantly less reactogenic than DTwP vaccines, their efficacy was disputed and remained unproven. First studies and epidemiological data from Japan suggested vaccine efficacy rates (VE) of about 80%; however, the first blinded clinical trial from Sweden documented a much lower VE. Worldwide, seven large DTaP efficacy trials have recently been completed. Our own efforts included a large safety trial with 22505 vaccinees and, nested in this setting, a prospective household contact study. Typical WHO-defined pertussis developed in 7 of 112 DTaP vaccinated children following household exposure as compared to 96 cases in 173 children not vaccinated against pertussis. Thus, vaccine efficacy was calculated to be 88.7% (95% CI 76.6 to 94.6). The median duration of spasmodic cough in the few children vaccinated with DTaP who did start coughing was 17 days as compared to 35 days in unvaccinated children. No waning of protection was observed. None of the confounding variables analyzed influenced study results in favour of DTaP. Following administration of more than 67000 DTaP doses, 153 serious adverse events were reported. Eight events were considered possibly related and five were considered related to the study vaccine. According to additional study results from the other trials it can be concluded that DTaP vaccines, like DTwP vaccines, are safe and effective. The choice between DTwP and DTaP should be based on acceptance of the reactogenicity profile, coverage rates achieved, costs and other factors in each individual country.

Clinical Trials as Topic↗
PubMed1996

Host defense within the urinary tract. I. Bacterial adhesion initiates an uroepithelial defense mechanism.

Uroepithelial defense has ben suggested to contribute to the local host resistance against ascending urinary tract infection. The cellular mechanism, however, is not known. In this study, bacterial growth was measured under the direct and indirect influence of uroepithelial cells. To study if a specific ligand-receptor interaction is required for uroepithelial cell (UEC) activation, isogenic Escherichia coli mutants expressing either mannose-sensitive, mannose-resistant (p), or mannose resistant (s) pili were tested for their capacity to induce the UEC defense mechanism. The antibacterial effect of UEC was abolished either by performing coculture in chambers with a fluid-permeable membrane which separates UEC from bacteria or by inhibiting membrane contact using the antiadherence factor pentosane polysulfate. No difference between the various types of pili could be shown. All E. coli strains adhered comparably to the UEC and were subsequently suppressed in their growth. Even a "naked" mutant without expression of common pili showed a similar behavior. In conclusion, bacterial growth suppression depends on direct contact between the UEC and bacteria, but is independent of common pili expressed on E. coli.

Adolescent↗
PubMed1996

Host defense within the urinary tract. II. Signal transducing events activate the uroepithelial defense.

It has been shown previously that the interaction between uroepithelial cells (UEC) from healthy donors and adherent. Escherichia coli suppresses bacterial growth in vitro. The following study was performed to investigate the nature of membrane signal transduction mechanisms involved in this process. UEC/E. coli cocultures were established in the presence of substances known to modulate transmembranous signals. Inhibition of calcium flux, either by calcium channel-blocking substances or by a calmodulin antagonist, depressed the antibacterial UEC function of "healthy" UEC. In contrast, receptor/ligand-induced stimulation of G-proteins, activation of the adenylate cyclase, and the increase of intracellular cyclic AMP levels by cytoplasmatic phosphodiesterase did not increase the antibacterial capacity of healthy UEC. However, the antibacterial function of defense-deficient UEC from patients with recurrent idiopathic urinary tract infection could be reconstituted by this treatment to almost normal levels. In conclusion, the antibacterial UEC defense function is activated by transmembranous signals from bacteria attached to the host cell surface. Activation involves the adenylate cyclase pathway. Activation of the phosphoinositol pathway may contribute to intracellular calcium fluxes.

Bacterial Adhesion↗
PubMed1996

Acellular pertussis vaccines: the rationale for an efficacy trial in Germany.

After concern about the safety of diphtheria-tetanus toxoid-whole cell pertussis vaccines (DTPw), the recommendation to vaccinate children with DTPw was withdrawn in 1974 in the former West Germany. This led pertussis cases to increase to an estimated 100,000 annually. Despite renewal of the vaccination recommendation in 1991, vaccine use remained low. The German health care structure assures regular contact between most children and pediatricians. This enabled the conduct of a large efficacy trial with a diphtheria-tetanus toxoid-acellular pertussis (DTPa) vaccine. Because a placebo-controlled trial was not ethically possible, a prospective household contact study with a blinded clinical follow-up was done. Possible study participants were screened by their pediatrician, who also initiated diagnostic procedures. Clinical follow-up was done by another locally based but independent and blinded physician. Vaccine efficacy was calculated to be 89% (95% confidence interval, 76.6%-94.6%). None of the identified confounding factors biased results in favor of the DTPa vaccine.

Clinical Trials as Topic↗
PubMed1996

Pertussis-specific cell-mediated immunity in infants after vaccination with a tricomponent acellular pertussis vaccine.

The aim of this study was to investigate pertussis-specific cell-mediated immunity in infants vaccinated with a tricomponent acellular vaccine. Infants were investigated during a primary vaccination schedule from the third month of life to the sixth month as well as before and after a booster at 15 to 24 months. This is the first report of specific cell-mediated immune responses to pertussis-related antigens in infants below the age of 12 months. Our data show that the vaccine induces T-cell responses specific for the vaccine components, detoxified pertussis toxin, filamentous hemagglutinin, and pertactin, that increase progressively over the course of the vaccination schedule. In contrast to declining antibody titers, cell-mediated immune responses are stable over the postprimary to prebooster period. Vaccination results in a progressive increase in the number of T cells that express activation marker CD45RO preferentially on CD4-positive T cells after stimulation with pertussis antigens. Measurements of cytokine secretion profiles demonstrated a preferential induction of interleukin 2- and gamma interferon-producing T-helper 1 cells and only low production of interleukin 10. The observed persistence of the specific cell-mediated immunity may have a bearing on the protective mechanisms induced by pertussis vaccination. Cell-mediated immunity requires further study, particularly to improve our understanding of the persistence of protection afforded by vaccination up to the administration of booster doses.

Antibodies, Bacterial↗
PubMed1994

Distribution of lymphocyte surface antigens in healthy neonates.

Using flow cytometric analysis we investigated the distribution of major lymphocyte surface antigens in newborn infants. A total of 221 newborns entered the study, of whom 53 fulfilled our criteria of healthy mature neonates. Percentages of immunofluorescent-positive cells were as follows (median and range from 25th to 75th percentiles given): for CD1 3.8%; 2.3%-5.8%. CD2 60.9%; 52.4%-66.8%. CD3 57.5%; 50.5%-63.3%. TcRass 57.7%; 48.1%-60.0%. CD4 36.3%; 28.0%-42.6%. CD8 23.0%; 20.0%-27.4%. CD11a 56.3%; 46.3%-68.5%. CD19 12.1%; 8.6%-14.8%. CD20 10.9%; 8.4%-12.9%. CD25 2.6%; 2.1%-4.5%. CDw52 61.0%; 51.2%-76.1%. CD71 5.2%; 3.1%-9.3%. While the ranges for the percentage of immunofluorescent-positive cells were rather small, there was a wide variation in the absolute numbers of marker immunofluorescent-positive cells.

Antigens, CD↗
PubMed1993

Glycosylation of alpha 1-acid glycoprotein in systemic onset juvenile rheumatoid arthritis and acute bacterial infection: value in differential diagnosis.

Agarose based affinity immunoelectrophoresis with free concanavalin A (Con-A) as ligand was used to examine the microheterogeneity of alpha 1-acid glycoprotein in sera of patients with systemic onset juvenile rheumatoid arthritis (JRA) and acute bacterial infections. In JRA, a decreased proportion of Con-A reactive alpha 1-acid glycoprotein variants was found when compared to healthy control. In contrast, acute bacterial infection showed an increased reactivity. Investigation of glycosylation may be useful in the differential diagnosis of systemic onset JRA and acute bacterial infection.

Acute Disease↗
PubMed1992

Flow cytometric immunophenotyping: principles and pitfalls.

Within the last decade flow cytometry (FCM) has become an integral part of basic immunological research. Elaboration of this technology has been intensively stimulated by a rapidly growing sophistication in monoclonal antibody technology and vice versa. At present numerous applications are established that allow an increasingly detailed insight into the immune system, however, automation still must be considered the "cinderella of the arts". Thus, transition of this powerful approach from a basic to a routine clinical procedure is much more difficult than expected. Sufficient usage of flow cytometers still requires some knowledge of physics and its technical applications. Moreover, several problems arise from the complexity of the biological systems investigated. Here we give a brief introduction to immunofluorescence and FCM followed by a discussion of six exemplary pitfalls that we hope will emphasise the general importance of methodological considerations.

Antibodies, Monoclonal↗
PubMed1992

Battered child syndrome: cerebral ultrasound and CT findings after vigorous shaking.

Child abuse by whiplash-shaking can lead to severe cerebral damage, neurological defects and mental retardation. Cerebral damage has been found with and without external evidence of head injury. We report the sonographic findings in two children after traumatization due to repetitive vigorous whiplash shaking. Cerebral sonography revealed cerebral edema at admission or within 48 hours thereafter. Follow-up studies demonstrated development of marked brain atrophy in both cases. The sonographic findings were confirmed by cranial computerized tomography. Doppler sonography was used to monitor cerebral perfusion by measuring intracranial blood flow. The clinical history of the patients demonstrates that cerebral sonography in combination with Doppler sonography not only serves as a diagnostic tool but also allows adjustment of therapy to the actual clinical status of the patient.

Battered Child Syndrome↗
PubMed1992

Determination of cardiac output by an angle and diameter independent dual beam Doppler technique in critically ill infants.

OBJECTIVE: To compare cardiac output measurements in critically ill infants by the dual beam Doppler and thermodilution techniques. DESIGN: Prospective direct comparison of the two techniques. For statistical evaluation one randomly assigned paired measurement of every patient was used. SETTING: Paediatric intensive care unit in a university hospital. PATIENTS: 18 infants after open heart surgery aged 4-25 months (weight 4-10 kg). INTERVENTIONS: Cardiac output measurements by dual beam Doppler and thermodilution techniques were performed within 10 minutes of each other and without knowledge of the results of the other methods. Multiple measurements were performed on some patients with a pharmacological or electrophysiological intervention or with a minimum of six hours between each pair of measurements. MEASUREMENTS AND MAIN RESULTS: Three patients were excluded because of an inadequate Doppler signal or a significant residual shunt. Cardiac output measurements ranged from 0.4 to 2.2 l/min for the thermodilution technique and from 0.5 to 2.1 l/min for the dual beam Doppler technique. Agreement between both methods was acceptable. The mean difference between the two methods was 0.026 l/min with two standard deviations ranging from -0.20 to 0.26 l/min. CONCLUSION: The dual beam Doppler technique was shown to have promise for the non-invasive determination of cardiac output in critically ill infants.

Cardiac Output↗
PubMed1992

[Monoclonal hybrid antibodies. New perspectives for basic research and tumor therapy].

Monoclonal hybrid antibodies are bi-specific constructs of two monoclonal antibodies with defined specificity. Hybrid antibodies can be used to force interactions between cell populations that under normal circumstances would not react with one another. Applications include the field of basic research as well as employment in therapy of malignancies and infectious diseases. The first part of this review describes the characteristic properties of hybrid antibodies and gives a short introduction into basic techniques for the production of these molecules. In the second part we present our observations on T-lymphocyte development studied with hybrid antibodies in fetal thymic organ cultures. Finally, we show that hybrid antibodies encompassing a binding site to the T-cell receptor and a binding site to a surface marker on tumor cells can be used to recruit cytotoxic T-cells to eliminate efficiently the malignant cells. Our data demonstrate that monoclonal hybrid antibodies are useful in the future development of new therapeutical principles, through facilitation of the immune response.

Antibodies, Monoclonal↗
PubMed1992

Effects of tolazoline and prostacyclin on pulmonary hypertension in infants after cardiac surgery.

OBJECTIVE: To evaluate the hemodynamic effects of tolazoline and prostacyclin in infants with pulmonary vasospasm after cardiac surgery. DESIGN: Prospective cohort study. SETTING: Pediatric ICU. PATIENTS: The cohort consisted of 42 infants and children with congenital heart disease and pulmonary hypertension who underwent corrective surgery and were monitored postoperatively using pulmonary artery catheters. Fourteen infants (2 to 12 months old) in this group required postoperative treatment with tolazoline or prostacyclin. INTERVENTIONS: Tolazoline was administered as a bolus of 0.5 mg/kg for treatment of persistent pulmonary hypertension or acute pulmonary hypertensive crisis. If its effectiveness was proved after 30 mins by hemodynamic measurements, a continuous iv infusion of 0.5 mg/kg/hr was established. Higher doses of tolazoline were avoided. If tolazoline treatment did not fulfill the criteria for pulmonary vasodilation, prostacyclin was given by continuous iv infusion at a starting rate of 5 ng/kg/min, followed by 10 ng/kg/min. In three patients, the infusion rate was increased to 15 ng/kg/min. RESULTS: Bolus administration of tolazoline resulted in a distinct pulmonary vasodilation in seven infants: mean pulmonary artery pressure and pulmonary vascular resistance decreased by an average of 35% and 45%, respectively. In these patients, tolazoline was infused over the following 12 to 72 hrs. One infant who received tolazoline for 72 hrs developed a clinically important gastrointestinal hemorrhage. In seven nonresponders to tolazoline, prostacyclin (PGI2) at an infusion rate of 5 ng/kg/min led to pulmonary vasodilation in five patients, at an iv infusion rate of 10 ng/kg/min in all seven infants studied. The latter dose of PGI2 reduced the mean pulmonary artery pressure by an average of 37%, and pulmonary vascular resistance by 43%. Transient withdrawal of prostacyclin in five infants demonstrated its short half-life and clinical effectiveness. Apart from a facial flush, no side-effects were encountered using PGI2 as an infusion over durations ranging from 12 to 504 hrs. CONCLUSIONS: These data suggest that, if tolazoline in a relatively low dose proves to be inefficient, prostacyclin can still be used as a safe and effective drug for treatment of pulmonary vasospasm. Prostacyclin offers more than a pharmacologic alternative to increased tolazoline dosages.

Drug Evaluation↗
PubMed1991

Schimke immuno-osseous dysplasia: a newly recognized multisystem disease.

On the basis of five cases personally observed and one previously reported, we describe a disorder characterized by skeletal dysplasia, rapidly progressive nephropathy, episodes of lymphopenia, and pigmentary skin changes. Defects of T-cell function were compatible with an autoimmune process. The disorder is probably of genetic origin and inherited as an autosomal recessive trait.

Antigens, CD↗
PubMed1991

Reduced CD4 and CD8 expression in human thymuses treated with soluble CD4.

Recent data suggest that accessory molecules like CD4 and CD8 act as co-receptors in intrathymic T-cell development. Soluble CD4 (sCD4) molecules offer a novel experimental approach to investigate the relevance of CD4 interaction with its putative intrathymic receptor for T-cell maturation. We attempted to inhibit binding of surface CD4 on thymocytes to its intrathymic receptor competitively by introduction of human sCD4 into human thymus tissue cultures. Our results demonstrate that sCD4, while not affecting peripheral T-cell responses as shown in control experiments, significantly affects intrathymic development of T lymphocytes. Immature CD4CD8 double positive (DP) thymocytes responded with reduced expression of both CD4 and CD8 molecules. This phenomenon could be followed up to the stage of single positive (SP) thymocytes: density of CD4 molecules on CD4 SP thymocytes and, even more interestingly, CD8 expression on CD8 SP cells, were reduced, indicating that the effect observed in immature DP thymocytes persists during their further development. Beyond that, analysis of T-cell receptor (TCR) expression in the low density CD4CD8 DP population revealed a slight decrease of alpha beta-TCR surface expression, suggesting a possible role of CD4 engagement in the generation of TCR in man. Since sCD4 is considered a therapeutical agent in HIV infections, these findings are not only of basic but also of clinical interest.

Antigens, Differentiation, T-Lymphocyte↗