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D Reinhardt

Publications and source records attributed to D Reinhardt.

At least 37 records · Page 2Linked to original sources
PubMed2004

Effects of inhaled formoterol compared with salbutamol in ventilated preterm infants.

BACKGROUND: Short-acting beta(2)-agonists have shown beneficial effects in preterm infants, but data on long acting beta(2)-agonists are still lacking. OBJECTIVES: To compare the effects of inhaled formoterol with salbutamol in preterm infants. METHODS: Randomized, double-blind, crossover design of salbutamol (100 microg every 6 h) or formoterol (12 microg every 12 h) delivered by metered dose inhaler on two consecutive days to very low birth weight infants on assisted mechanical ventilation (n=12; gestational age 25.7+/-2 weeks; birth weight 720+/-254 g; postnatal age 25+/-9 days; mean+/-SD). Treatment with the second drug was administered until day 7 in eight infants. Outcome variables were minute volume MV, respiratory mechanics, heart rate HR, blood pressure, serum potassium and blood glucose levels. RESULTS: Mean MV increased by maximal 26% (salbutamol) and by 22% (formoterol) differing from baseline values until 6 and 8 h through increased mean tidal volume (Vt) in both groups (max. 14%). Mean static compliance (Crs) increased by 26% (salbutamol) and by 32% (formoterol) until 60 min post-administration. There was no tachyphylaxis. CONCLUSION: Inhaled salbutamol and formoterol equally increase MV, Vt, Crs and HR in mechanically ventilated infants with a longer lasting systemic effect of formoterol.

Administration, Inhalation↗
PubMed2004

Increasing mixed chimerism defines a high-risk group of childhood acute myelogenous leukemia patients after allogeneic stem cell transplantation where pre-emptive immunotherapy may be effective.

Children with leukemias and increasing mixed chimerism (increasing MC) after allogeneic stem cell transplantation have the highest risk to relapse. Early immunological intervention was found to be effective in these cases. To substantiate this on a defined group of pediatric acute myelogenous leukemia (AML) patients, we performed serial analysis of post transplant chimerism and pre-emptive immunotherapy in patients with increasing MC. In total, 81 children were monitored, 62 patients revealed complete chimerism (CC), low-level MC or decreasing MC. Increasing MC was detected in 19 cases. Despite early immunological intervention relapse was still significantly more frequent in patients with increasing MC (9/19) than in patients with CC, low-level or decreasing MC (8/62, P<0.005). The probability of 3-year event-free survival (EFS) was 52% for all patients (n=81), 59% for patients with CC, low-level MC, 60% for patients with decreasing MC (n=62), and 28% for patients with increasing MC (n=19, P<0.005). Patients with increasing MC who received early immunological intervention showed a significantly enhanced probability for event-free survival (pEFS 36%, n=15) compared to patients with increasing MC without intervention (pEFS 0%, n=4, P<0.05). These results prove that pediatric AML patients with increasing MC are at highest risk for relapse and that early immunological intervention can prevent relapse in these patients.

Adolescent↗
PubMed2004

Infectious complications in pediatric acute myeloid leukemia: analysis of the prospective multi-institutional clinical trial AML-BFM 93.

Infections still remain a major cause of therapy-associated morbidity and mortality in children with acute myeloid leukemia (AML). To improve supportive care measurements, detailed information on frequency and characteristic features of infectious complications is needed. We retrospectively analyzed the medical charts of 304 children, treated in 30 hospitals according to the multi-institutional clinical trial AML-BFM 93. Overall, 855 infectious complications occurred in 304 patients (fever without identifiable source (n=523; 61.2%), clinically (n=57; 6.7%) and microbiologically documented infections (n=275; 32.1%)). Neutropenia was present in 74.1% of the infectious episodes. In all, 20 patients died of infection-associated complications (15/276 (5.4%) patients without and 5/28 (17.9%) with Down syndrome), most of them during early induction therapy (n=11). Blood stream infections occurred in 228 episodes (Gram-positive (n=202) and Gram-negative (n=42) pathogens). Invasive fungal infection was probable or proven in 15 patients. In 113 out of the 855 infectious episodes (13.3%), pneumonia was radiologically diagnosed. Better strategies of supportive care might help to improve overall survival in children undergoing chemotherapy for AML. Therefore, children with AML should be treated in specialized pediatric centers, and there should be a very low threshold to readmit patients, in particular patients with pulmonary symptoms.

Acute Disease↗
PubMed2004

Caesarean section and gastrointestinal symptoms, atopic dermatitis, and sensitisation during the first year of life.

AIMS: To investigate the effect of caesarean section on gastrointestinal symptoms, atopic dermatitis, and sensitisation to nutritional allergens in infants. METHODS: A total of 865 healthy full term neonates with parental history of allergy participating in the prospective German Infant Nutritional Intervention Program (GINI) were exclusively breast fed during the first four months of life and had a one year follow up. Data were obtained by follow up visits at age 1, 4, 8, and 12 months, weekly diaries for the first six months, and measurement of total and specific IgE at birth and 12 months. RESULTS: Infants born by caesarean section (147/865, 17%) had a greater risk of diarrhoea (OR(adj) 1.46, 95% CI 1.022 to 2.10) and sensitisation to food allergens, both in adjusted (OR(adj) 2.06, 95% CI 1.123 to 3.80) and stratified analyses (by cord blood IgE). Caesarean delivery was not associated with colicky pain and atopic dermatitis. CONCLUSION: Caesarean delivery might be a risk factor for diarrhoea and sensitisation in infants with family history of allergy. Further research in this area seems warranted as choosing caesarean section becomes increasingly popular.

Adult↗
PubMed2004

Gemtuzumab ozogamicin (Mylotarg) in children with refractory or relapsed acute myeloid leukemia.

BACKGROUND: Gemtuzumab ozogamicin (GO) is an immunoconjugate consisting of the CD33 antibody and calicheamicin, a potent cytotoxic agent. Developed for targeted treatment of CD33-positive AML, studies in adults showed its efficacy in relapsed and refractory AML. PATIENTS AND METHOD: We report 12 children with multiple relapsed or refractory AML receiving GO as compassionate use. 11 children had initially been treated according to the AML-BFM 93 or 98 protocol, 1 girl received relapse treatment (liposomal daunorubicin/FLAG) due to secondary AML. After relapse, 10 children received an intensive relapse therapy (AML-BFM 97 or international AML-Relapse Study 2001/01). 2 of them had been transplanted in first or second CR before GO therapy. RESULTS: 5 of 12 children responded to treatment with blast reduction to below 5%, but no child achieved CR after GO. Time until reoccurrence of blasts in almost all children with GO response was 3-8 months. In 5 children stem cell transplantation (SCT) was performed after GO therapy. 4 of them suffered from further progression of AML, 1 boy is in second remission with a follow-up of 8 months. 2 children had severe side effects. An anaphylactic reaction with severe hypotension was managed by catecholamine support and intensive care. In 1 girl, who relapsed after SCT in first remission, a veno-occlusive disease of the liver occurred, but could be treated successfully with defibrotide. CONCLUSION: GO therapy can induce blast reduction in children who have no further conventional treatment options. Frequency and severity of adverse events are limited, and therapy seems to be feasible for children with a sufficient general condition. Controlled studies are necessary to learn more about efficacy and side effects, especially implications for further therapy.

Acute Disease↗
PubMed2003

Monitoring of minimal residual disease (MRD) by real-time quantitative reverse transcription PCR (RQ-RT-PCR) in childhood acute myeloid leukemia with AML1/ETO rearrangement.

The fusion transcript AML1/ETO corresponding to translocation t(8;21)(q22;q22) can be found in approximately 7-12% of childhood de novo AML. Despite the favorable prognosis, some of these patients relapse. Most of MRD studies so far were performed on adults treated not uniformly. Therefore, we analyzed the follow-up of 15 AML1/ETO-positive children using real-time quantitative reverse transcription PCR (RQ-RT-PCR), all enrolled in the multicenter therapy trial AML-BFM 98. AML1/ETO copy numbers were normalized to the control gene ABL and the results were expressed in copy numbers AML1/ETO per 10 000 copies ABL. At diagnosis, a median of 10 789 copies AML1/ETO was found. A linear decrease to about 10 copies (2-4 log) could be seen in most of the children by the start of consolidation. In the majority of cases they remained positive at this low level during the ongoing therapy. Four children relapsed and two of them had a decrease of less than 2 log before starting consolidation. Three of the relapsed children showed, prior to relapse, an increase of the AML1/ETO fusion transcript at 6, 9, and 11 weeks, respectively. These results suggest that monitoring of minimal residual disease using RQ-RT-PCR could be helpful in detecting patients with a higher risk of relapse.

Adolescent↗
PubMed2003

Chemokine receptor 5 expression in gastric mucosa of Helicobacter pylori-infected and noninfected children.

Experimental data from human adults or animal models indicate that the Helicobacter pylori-specific immune response is dominated by inflammatory T cells of the Th1 type. To investigate whether a Th1 immune response is established in early H. pylori infection, gastric biopsy samples from 70 children were subjected to immunohistochemical analysis. To this end, T cells, B cells, monocytes, neutrophils, and chemokine receptor 5 (CCR5)-expressing (CCR5(+)) cells, which are associated with Th1 immune responses, were quantified. Children were classified according to H. pylori status and clinical, laboratory, and macroscopic (during endoscopy) findings, without knowledge of histological findings. Group 1 included 31 H. pylori-infected children, group 2 contained 24 children with other conditions possibly affecting the stomach, and group 3 contained 15 children without verifiable pathological findings in the stomach. Lymphoid follicles were present in 90% of biopsy samples from group 1 and 48% of those from group 2 but absent in group 3 biopsy samples. Intraepithelial T cells and CCR5(+) cells were regularly detected in all groups without significant differences. B cells, monocytes, and neutrophils were not found. In contrast, the numbers of lamina propria T cells (P < 0.003) and CCR5(+) cells (P < 0.001) were increased significantly in H. pylori-infected children. B cells (in 13 of 66 children) were detected in children with active (n = 11) or previously cleared (n = 2) H. pylori infections but were absent in healthy children. The numbers of monocytes (in 10 of 67 children) did not differ among the groups. Calculations indicated that the majority of gastric T cells express CCR5; this finding is in contrast to the low percentage of CCR5(+) T cells in the peripheral circulation. Thus, an increase in the numbers of CCR5(+) cells in H. pylori-infected stomach mucosa suggests that this molecule may play an important role in gastric immune responses.

Adolescent↗
PubMed2003

Hereditary haemorrhagic telangiectasia: a questionnaire based study to delineate the different phenotypes caused by endoglin and ALK1 mutations.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterised by mucocutaneous telangiectasis, epistaxis, gastrointestinal haemorrhage, and arteriovenous malformations in the lung and brain. Causative mutations for HHT have been identified in two genes, endoglin and ALK1, which encode proteins involved in serine-threonine kinase signalling in the endothelial cell. METHODS: A number of people affected with HHT had completed a postal questionnaire as part of an international study to delineate the HHT phenotype. We identified questionnaires completed by subjects in whom we had identified a mutation in endoglin or ALK1. Further questionnaires were sent to families with known mutations. Data were only included from questionnaires returned by people known to carry disease causing mutations. RESULTS: Questionnaires were completed by 83 subjects with known mutations. Of these, 49 had endoglin mutations (HHT1) and 34 had ALK1 mutations (HHT2). Subjects with HHT1 reported an earlier onset of epistaxis (p=0.01) and telangiectasis (p=0.0001) than those with HHT2. Pulmonary arteriovenous malformations were only reported in the endoglin mutation group in our study (p<0.001). CONCLUSIONS: Our questionnaire based study provides evidence that the HHT phenotype caused by mutations in endoglin (HHT1) is distinct from, and more severe than, HHT caused by mutations in ALK1 (HHT2). This has significant implications for diagnosis, screening, and treatment in the two different forms of HHT, as well as for understanding the pathogenesis of the disease.

Activin Receptors, Type I↗
PubMed2002

Eradication of initial Pseudomonas aeruginosa colonization in patients with cystic fibrosis.

The optimal treatment for the eradication of initial P. aeruginosa infection in CF is still unclear. Recently long-term inhaled tobramycin has been proposed. Here we report the results with brief inhaled and/or systemic anti-pseudomonal treatments. Initial P. aeruginosa colonization was successfully eradicated as demonstrated by negative repetitive throat cultures or sputa and serum antipseudomonal antibodies in 15 of 17 patients for at least two years. Randomized, controlled trials are urgently needed to define the optimal protocol for the eradication of P. aeruginosa. Pseudomonas aeruginosa, infection, treatment, antibodies; inhaled tobramycin

Administration, Inhalation↗
PubMed2002

Isolated myelosarcoma in children--update and review.

Primary myelosarcomas, also called leukemia cutis, granulocytic sarcomas or chloromas, are rare extramedullary manifestations of acute myeloid leukemia (AML) which precede bone marrow involvement. Skin infiltration was the most frequent localization associated with a myelomonocytic differentiation. Although first remission was achieved by most children, risk of relapse seemed to be increased. This might be caused by the specific biology of myelosarcomas, but also may be the result of delayed or reduced treatment. During the AML-BFM-studies 87/93/98 (11/1987-7/2000) 37 children with isolated myelosarcomas were diagnosed. Eighteen of the 37 patients survived with a 5-year overall survival estimation of 0.54+/-0.09 compared to 0.59+/-0.02; p(log rank) = 0.94. However, reduced or delayed treatment in 17 children led to an increased relapse rate of 71% compared to 35% in children treated soon after diagnosis. The 5-year overall survival in these patients was 0.41+/-0.11. According to our experience and review of the literature, an early diagnostic workup is needed in children with unusual skin lesions or tumors, considering myelosarcoma as primary manifestation of AML. Intensive AML-specific chemotherapy is generally recommended soon after diagnosis.

Acute Disease↗
PubMed2002

Maternal compliance with nutritional recommendations in an allergy preventive programme.

AIMS: To assess maternal compliance with nutritional recommendations in an allergy preventive programme, and identify factors influencing compliance behaviour. METHODS: Randomised double-blind intervention study on the effect of infant formulas with reduced allergenicity in healthy, term newborns at risk of atopy. Maternal compliance with dietary recommendations concerning milk and solid food feeding was categorised. RESULTS: A total of 2252 newborns were randomised to one of four study formulas. The drop out rate during the first year of life was 13.5% (n = 304). The rates of high, medium, and low compliance to milk feeding during weeks 1-16 were 83.4%, 4.0%, and 7.5%; the corresponding rates to solid food feeding during weeks 1-24 were 60.0%, 12.1%, and 22.9%. In 5.1% of subjects no nutritional information was available. Low compliance was more frequent among non-German parents, parents with a low level of education, young mothers, smoking mothers, and those who weaned their infant before the age of 2 months. CONCLUSIONS: Evaluation of allergy preventive programmes should take into account non-compliance for assessing the preventive effectiveness on study outcome.

Adult↗
PubMed2002

Cardiac remodelling in end stage heart failure: upregulation of matrix metalloproteinase (MMP) irrespective of the underlying disease, and evidence for a direct inhibitory effect of ACE inhibitors on MMP.

OBJECTIVE: To investigate matrix metalloproteinases (MMP-2 and MMP-9) in heart failure caused by ischaemic and idiopathic dilated cardiomyopathy, and the impact of angiotensin converting enzyme (ACE) inhibition on MMP. DESIGN AND MAIN OUTCOME MEASURES: MMP were extracted from myocardium of patients with heart failure (coronary artery disease, n = 13; idiopathic dilated cardiomyopathy (IDCM), n = 16) and from controls (n = 6). The active form of MMP-2 and MMP-9 was measured by enzyme linked immunosorbent assay; activity of MMPs by zymography; mRNA expression of MMPs by reverse transcriptase polymerase chain reaction. RESULTS: Active MMP-9 was significantly increased in coronary artery disease (mean (SD) 1.6 (0.35) ng/ml) and IDCM (2.11 (0.54) ng/ml) in comparison with controls (0.53 (0.15) ng/ml). Increased MMP-2 was only found in IDCM (3.68 (0.41) ng/ml). There were corresponding increases in MMP activity but no upregulation of mRNA expression was found. The ACE inhibitors captopril and ramiprilate inhibited MMP-2 and MMP-9 activity in vitro (inhibitory capacity (IC50), in mmol/l: MMP-2: captopril 2.0 (0.16), ramiprilate 2.1 (0.3); MMP-9: captopril 1.65 (0.18), ramiprilate 2.0 (0.3)). Lisinopril inhibited MMP-9 significantly but did not inhibit MMP-2 in vitro (IC50 MMP-2: 7.4 (0.88); MMP-9: 7.86 (2.23)). Inhibition of MMP activity by ACE inhibitors was blunted by zinc excess. CONCLUSIONS: Upregulation of MMP-9 activity is common in the failing myocardium, independent of the underlying disease. Missing upregulation of transcription suggests that activation of latent forms of MMP is the source of increased MMP activity, rather than increased de novo synthesis. Some ACE inhibitors may influence MMP activity by a direct effect.

Adult↗
PubMed2002

Traffic-related air pollution and respiratory health during the first 2 yrs of life.

As part of an international collaborative study on the impact of Traffic-Related Air Pollution on Childhood Asthma (TRAPCA), the health effects associated with long-term exposure to particles with a 50% cut-off aerodynamic diameter of 2.5 microm (PM2.5), PM2.5 absorbance, and nitrogen dioxide (NO2) were analysed. The German part of the TRAPCA study used data from subpopulations of two ongoing birth cohort studies (German Infant Nutrition Intervention Programme (GINI) and Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children (LISA)) based in the city of Munich. Geographic information systems (GIS)-based exposure modelling was used to estimate traffic-related air pollutants at the birth addresses of 1,756 infants. Logistic regression was used to analyse possible health effects and potential confounding factors were adjusted for. The ranges in estimated exposures to PM2.5, PM2.5 absorbance, and NO2 were 11.9-21.9 microg m(-3), 1.38-4.39 x 10(-5) m(-1), and 19.5-66.9 microg x m3, respectively. Significant associations between these pollutants and cough without infection (odds ratio (OR) (95% confidence interval (CI)): 1.34 (1.11-1.61), 1.32 (1.10-1.59), and 1.40 (1.12-1.75), respectively) and dry cough at night (OR (95% CI): 1.31 (1.07-1.60), 1.27 (1.04-1.55), and 1.36 (1.07-1.74), respectively) in the first year of life were found. In the second year of life, these effects were attenuated. There was some indication of an association between traffic-related air pollution and symptoms of cough. Due to the very young age of the infants, it was too early to draw definitive conclusions from this for the development of asthma.

Air Pollution↗