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Biomedical subjects

M Knuf

Publications and source records attributed to M Knuf.

32 records · Page 2Linked to original sources

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↗

Clinical experience of a tricomponent acellular pertussis vaccine combined with diphtheria and tetanus toxoids for primary vaccination in 22,505 infants.

OBJECTIVES: To assess the safety and tolerability of 12 lots of SmithKline Beecham Biologicals' diphtheria-tetanus-tricomponent acellular pertussis vaccine (DTaP) in a large cohort of 22,000 vaccinees, with detailed analyses of reactivity, immunogenicity, and immune response to pertussis toxin in subsets. METHODS: In a prospective, double-blind, multicenter trial in Germany, 22,505 healthy infants received three vaccinations of DTaP at age 3, 4, and 5 months. Serious adverse events were followed for 1 month after each vaccination, and neurologic events for 1 year or longer. Serum IgG antibodies were assayed before vaccination and 1 month after vaccination. RESULTS: After 67,000 doses, 153 serious adverse events (0.23%) were reported, 8 considered possibly related, and 5 related to vaccination, including 1 hypotonic-hyporesponsive episode. Incidence rates of sudden infant death syndrome (7; 0.01%) or acute neurologic events (20; 0.030%) were no higher than expected and not considered to be related to vaccination. Redness and swelling of 20 mm or greater occurred after 44 (0.6%) and 40 (0.6%) of the 7270 doses, respectively, and high fever (> 39.5 degrees C) in 6 (0.08%) subjects within 48 hours of vaccination. In the immunogenicity analysis of 580 infants, 98% responded to pertussis toxin, 96% to filamentous hemagglutinin, and 98% to pertactin. In an additional 5712 infants, the response rate to pertussis toxin was 99%. CONCLUSIONS: In a large cohort of 22,505 infants vaccinated, SmithKline Beecham Biologicals' tricomponent DTaP vaccine was shown to be safe, well-tolerated, and immunogenic for all component antigens.

Diphtheria-Tetanus-Pertussis Vaccine↗

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↗

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↗

[Pre- and postpartum ultrasound examinations for diagnosis of urogenital abnormalities].

BACKGROUND: The aim of the study was to evaluate prenatal and postpartal sonographic investigations to diagnose congenital uropathies. PATIENTS/METHODS: The Mainz birth defect monitoring system, the "Mainzer Model", was launched in 1990. Over a period of five years (1/90 to 1/95) 19,028 newborns underwent postpartal sonographic examination. Anamnestic data including prepartal sonographic examination were collected. According to a defined ultrasound criteria list, ultrasound findings were considered normal in 94.8% of the neonates, 4.4% were defined as requiring a follow-up examination and 0.8% were pathological. In the current study we analyzed patients with pathological findings with their pre- and postpartal sonographic investigations as well as their clinical data (urinary tract infections, operative procedures). RESULTS: In the study group prenatal ultrasonography showed evidence of severe anomalies only in 51 fetuses (32.9%). Surgical correction was required in 39 cases. 20 (51%) have been diagnosed prenatally. 28 patients presented with urinary tract infections. Out of this group only 11 patients have been detected by prenatal ultrasound. CONCLUSION: In conclusion, postnatal ultrasound is more effective to diagnose anomalies of the urinary tract. To prevent complications i.e. urinary tract infections a neonatal screening program would be valuable.

Female↗

[Transcatheter occlusion of the persisting arterial duct].

BACKGROUND: Transcatheter occlusion of the persisting arterial duct (PDA) is feasible using different techniques like coil-embolization (CE), Rashkind PDA occluder (Rash), Amplatzer Duct Occluder (ADO). Comparative studies with this devices in relation to the size of the PDA and the device are missing. Aim of this study was to evaluate the different systems at the own patient population. PATIENTS AND METHODS: From 1993 to 12/2001 transcatheter occlusion was attempted in 92 patients aged 4,13 years (range 0,07 to 14,39 years) using CE, Rash or ADO. All patients received echocardiographic examinations 24 hours before and after intervention, after 3, 6, and 12 months and than yearly. RESULTS: 91/92 PDAs could be successfully closed by 97 interventions. There were 63 CE, 25 Rash and 9 ADO performed. Primary closure rate was 75 % for Rash, 80 % for ADO and 80,8 % for CE (n. s.) and after 6 months 88 % for Rash, 92,3 % for CE and 100 % for ADO (p < 0,001), although the size of the PDA increased significantly from CE (2,14 + 1,1 min) to Rash (3,2 +/- 1,3 min) to ADO (4,9 +/- 1,9 min) (p < 0.05). In 6/7 pts with residual shunts complete occlusion could be achieved by second intervention. CONCLUSION: In dependency of the size of the PDA and the right choice of the occluder almost all PDAs are closable with transcatheter techniques.

Cardiac Catheterization↗

[Lymphadenitis colli due to non-tuberculous mycobacteria (NTM): a case-series and review of the literature].

OBJECTIVE: Lymphadenitis colli due to NTM should always be considered in children with cervical Lymphadenitis. For Germany there is a lack of data concerning the incidence, the epidemiology, the diversity and frequency of the different bacteria, the diagnosis, the clinical manifestation and the medical treatment. METHODS: By means of a questionnaire, which was retrospective for 1985 to 1994 and was sent to 277 children's hospitals in Germany, we collected data on Lymphadenitis colli in Germany. In our study we also incorporated cases from the "National Laboratory for Mycobacteria" in Borstel as well as six cases from our hospital in Mainz. Therefore our data includes both clinical (28) and laboratory (30) cases. Additionally we screened the literature on "Lymphadenitis colli in children due to NTM". RESULTS: A total of 51 cases of Lymphadenitis due to NTM could be identified. The illness occurs typically in young children up to six years of age. The most frequent cause were species of the Mycobacterium avium-intracellulare-scrofulaceum complex. Except for the local diagnosis of a cervical Lymphadenitis other clinical symptoms are missing, just as specific laboratory parameters with a subacute or chronic course. The tuberculin skin test can be false positive. The diagnosis is confirmed by biopsy and histology as well as through microbiological tests. CONCLUSIONS: The best treatment is complete surgical excision, whereas the importance of additional or exclusive treatment with Clarithromycin, Rifabutin and other antibiotics could not be clarified completely. But in patients with AIDS Rifabutin and other drugs could perhaps be useful, even for prophylaxis. Also if complete excision is impossible, treatment with certain drugs (Clarithromycin or Azithromycin in combination with Rifampicin) will be recommended. It still remains in question if NTM infections in children are really increasing.

Acquired Immunodeficiency Syndrome↗

[Griscelli syndrome: a case report].

BACKGROUND: Griscelli syndrome is a rare disorder with poor prognosis. It is characterized by silver-grey hair or strands of silver-grey hair in childhood, and variable cellular immunodeficiency. The course of the untreated disease is fatal. Recurrent episodes of fever and lymphohistocytic infiltration of organs lead to hepatosplenomegaly, lymphadenopathy, pancytopenia, and progressive neurological impairment. Prognosis on morbidity and lethality depends on an early diagnosis. PATIENT: The girl we report on suffers from Griscelli syndrome. She developed normally and only her grey strands of hair, grey eyebrows, and eyelids were conspicuous. With the age of 4 years, she presented with a first episode of illness. RESULTS: Cytostatic treatment seemed to ameliorate the course of the disease although further accelerated phases could not be prevented. The only therapeutic option is a bone marrow transplantation, which we conferred upon our patient. CONCLUSION: The finding of grey hairs in childhood should alert clinicians to consider Griscelli syndrome since an early diagnosis is life and health saving.

Administration, Oral↗

[Linezolid in two premature babies with necrotizing enterocolitis and infection with vancomycin-resistant enterococcus].

The use of the antibiotic Linezolid in two premature babies with necrotizing enterocolitis and infection with vancomycin-resistant enterococcus is described. Therapy with Linezolid in cause of necrotizing enterocolitis is an exception. Actually there are no proven recommendations for the use in this age group. Despite the successfully results more investigations for the use of linezolid in newborns and prematures are necessary.

Acetamides↗

[Anaphylaxis after vaccination due to hypersensitivity to gelatin].

Most allergic reactions after vaccination occur in patients sensitive to egg protein. Therefore this subject is well investigated, and the majority of common vaccines today contain only traces of egg protein. In contrast, there is little knowledge of hypersensitivities to other substances frequently contained in vaccines, e. g. antibiotics, phenol, gelatin and different preservatives. Here we report the case of a boy who had an anaphylactic reaction after being vaccinated against measles, mumps, rubella (MMR), and tick-born encephalitis (TBE) simultaneously. Different tests finally revealed a hypersensitivity to gelatin. This should be kept in mind especially during emergency care, since gelatin containing products like Haemaccel, Gelifundol or Gelofusin are widely used as colloid for resuscitation. If type 1 reactions after vaccination occur, gelatin should be taken into account as the causative agent. A medical alert card is recommended for such patients.

Anaphylaxis↗

[Impact of universal varicella vaccination in Germany: an epidemiological and economic analysis].

Varicella is a highly contagious viral disease which mainly affects young children and usually is perceived as infection with a mild disease course. However, there is increasing evidence indicating that the morbidity and mortality as well as the economic impact associated with varicella are significant. While universal childhood vaccination against varicella is currently not recommended in Germany, the availability of safe and efficacious vaccines offers the opportunity for preventive intervention. Detailed and reliable data on the consequences of varicella and the possible impact of a universal vaccination program are missing to date for Germany. In order to generate this information, we conducted a comprehensive evaluation. The objective was to quantify the medical consequences and the economic impact of varicella on third-party payers and the society by means of a model analysis, and particularly to assess the effects of various universal vaccination strategies. The study confirms that varicella represents a significant health and economic burden in Germany. Following mathematical modelling, universal varicella vaccination for children at the age of 12-18 months could prevent more than 82 % of cases and complications on average per year. Economically, universal vaccination would lead to net cost savings not only for the society but also for the third-party payers. From these findings it can be concluded that universal varicella vaccination is a strategy which should be encouraged, from a medical, epidemiological, but also economic viewpoint.

Chickenpox↗

[Preparation of a compatibility chart for intravenous drug therapy in neonatal and pediatric intensive care units].

BACKGROUND: Modern neonatal and pediatric intensive care includes a sophisticated pharmacotherapy with numerous drugs, mainly administered intravenously. Often, despite the use of multi-lumen central venous lines, more peripheral venous accesses are required. To reduce the necessity of numerous venous lines on one hand and on the other hand to avoid complications from incompatibilities of the administered drugs, we compiled a compatibility chart, encompassing more substances than covered in previously available charts. METHODS: Information on compatibility of commonly prescribed drugs was collected by analysis of manufacturers' information, medical and pharmaceutical handbooks, and a literature research. RESULTS: Available data on compatibility of 78 drugs were displayed in a two-dimensional chart. Beside the pH of each drug, compatibility of drug combinations was encoded for simultaneous infusion. Special emphasis was on security of the therapy. CONCLUSION: The compatibility chart gives quick reference for Data on compatibility of intravenously administered drugs in neonatal and pediatric intensive care.

Catheterization, Central Venous↗

[Granulocyte function in premature infants before the 34th week of pregnancy and in mature newborn infants].

BACKGROUND: Preterm and term neonates have an increased risk to develop severe bacterial infections. Impairment of neutrophil function may be responsible for this increased risk. Other diseases related to prematurity like retinopathia of prematurity (ROP) or broncho-pulmonary dysplasia (BPD) on the other hand may be due to poorly controlled O2-radical production. PATIENTS AND METHODS: Blood samples of 112 premature (34 weeks of gestation and older) and term neonates were analysed. Blood samples of 23 healthy adults (18 to 50 years old) served as controls. O2-radical production and phagocytosis of neutrophils were determined by flow cytometry, using a commercial test system. RESULTS: Under the experimental conditions applied, the capacity to produce O2-radicals following vigorous stimulation (E. coli) is comparable between neutrophils of preterm/term neonates and healthy adults. However, unstimulated or weakly stimulated (fMLP) neutrophils of preterm and term neonates show a statistically higher O2-radical production as neutrophils of the control group. The production of oxygen radicals increases during the first 10 days of the life. The capability of neutrophils to phagocytose E. coli is significantly lower in newborns (preterm and term) compared to the adult controls. CONCLUSIONS: The values reported here for phagocytosis and O2-radical production utilizing a commercially available test system may serve as "preliminary normal values" for neonates. No differences were found between the groups of neonates with and without infection. Impaired neutrophil-phagocytosis possibly contributes to the increased risk of preterm and term neonates to acquire bacterial infections. The increased spontaneous O2-radical production, on the other hand, may play a role for the development of so called "free radical diseases" such as ROP or BPD. However, our results cannot add further proof to this hypothesis.

Adult↗