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Invasive fungal disease (IFD) causes increasing morbidity and mortality in haematological cancer patients. Reliable cost data for treating IFD in German hospitals is not available. Objective of the study was to determine the institutional cost of treating the IFD. Data were obtained by retrospective chart review in German hospitals. Patients had either newly diagnosed or relapsed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Direct medical cost was calculated from hospital provider's perspective. A total of 108 patients were enrolled at 5 tertiary care hospitals, 36 IFD patients and 72 controls. The vast majority of IFD patients (74%) were diagnosed with invasive aspergillosis. On average, the hospital stay for IFD patients was 12 days longer than in control patients. All patients in the IFD group and 89% of patients in the control group received antifungal drugs. Mean direct costs per patient were €51 517 in the IFD group and €30 454 in the control group. Incremental costs of €21 063 were dominated by cost for antifungal drugs (36%), hospital stay (32%) and blood products (23%). From the perspective of hospitals in Germany the economic burden of IFD in patients with AML or MDS is substantial. Therefore, prevention of IFD is necessary with respect to both clinical and economic reasons. [ABSTRACT FROM AUTHOR]

Background. Bacterial, viral, and fungal pathogens frequently cause severe, life-threatening infections in immunocompromised patients after allogeneic hematopoietic stem cell transplantation (SCT). Objective. To compare the frequency of infections in patients with matched-related (Group A) or with human leukocyte antigen (HLA)-matched-unrelated donors (Group B). Patients and methods. Patients treated at our transplantation unit between April 2004 and April 2005 were enrolled into this analysis. Documentation comprised demographic data, conditioning treatment, stem cell source, clinical course, as well as microbiological and clinical data and mortality. Results. We analyzed 59 patients, 22 in Group A and 37 in Group B. Both groups were well balanced regarding demographic data. Diagnoses were acute myeloid leukemia (30 of 59 patients, 50.8%), multiple myeloma (15.2%), acute lymphoblastic leukemia (11.9%), and chronic myeloid leukemia (10.2%). Patients in Group A developed infections in 95.5% of the cases compared with 97.3% in patients in Group B. Most frequently detected pathogens were Staphylococcus species, human herpesvirus-6, and Epstein–Barr virus. Three proven fungal infections were detected in Group A compared with 9 proven fungal infections in Group B. Lung infiltrations were observed in equivalent incidence in both groups. Two years after transplantation, 55.9% of patients were alive (Group A: 68.2%; Group B: 48.6%, not significant). Conclusion. Allogeneic SCT from HLA-matched-unrelated donors does not have a higher infection risk than patients transplanted from matched-related donors. [ABSTRACT FROM AUTHOR]

Cow’s milk protein allergy (CMPA) is best treated by complete elimination of cow’s milk from the diet. For infants with CMPA who cannot be breast-fed, formulas based on extensively hydrolyzed proteins or on amino acids are the preferred substitutes for cow’s milk-based formulas. In this study, we compared the tolerance and growth of infants with CMPA who were fed a new extensively hydrolyzed formula containing lactose (eHF) with those who were fed an amino acid formula (AAF). This was a prospective, multi-center, randomized, reference-controlled study. Seventy-seven infants <12 months old with suspected CMPA were enrolled. In 66 of these, CMPA was confirmed by oral challenge in a double-blind, placebo-controlled food challenge (DBPCFC) or by a medical history of severe allergic reaction to cow’s milk and a positive skin prick test. These infants were then tested for their reaction to eHF and AAF in a DBPCFC. All infants tolerated both formulas and were randomized to receive either eHF (n = 34) or AAF (n = 32) for 180 days. Growth (weight, length, and head circumference) and tolerance [skin, gastro-intestinal, and respiratory tract symptoms of allergy] were evaluated after 30, 60, 90, and 180 days. There were no significant differences between the two groups in any of the growth measurements. Length and head circumference were similar to Euro-growth standards, but weight was slightly lower. Gastro-intestinal and respiratory tract symptoms of allergy were also similar in the two groups. However, whereas SCORAD scores for atopic dermatitis remained constant throughout the study in infants-fed eHF, there was a slight decrease in those fed AAF. Infants-fed eHF had significantly fewer incidents of vomiting than infants-fed AAF and a significantly higher frequency of soft stools. The new eHF is safe and well tolerated in infants diagnosed with CMPA. [ABSTRACT FROM AUTHOR]

Regarding declining resources epidemiological data on needs for oral rehabilitation are required. Within the framework of an oral health survey a non-stratified two-stage random sample was taken to represent the over 14-year-old population of Saxony/Germany. The participation rate was 55%. Normative need was determined by dental assessment and guidelines developed in a consensus process, subjective prosthetic treatment need by self-complete questionnaire. About 97% of the realized sample could be planned within the guidelines. About 81% had normative prosthetic treatment need. Compared with the rate of normative need the rate of subjective need (13%) was considerably lower (χ2P < 001). Different predictive parameters of subjective need were identified by logistic regression. Besides other factors subjective need was associated with giving dentist’s recommendation as significant reason for prosthetic restorations [odds ratio (OR)=543], not believing that the own teeth were all right (OR=017), and the existence of prosthetic restorations (OR=387 for fixed restorations; OR=405 for removable dentures). The guidelines proved their suitability to assess normative prosthetic treatment need in oral health surveys. Further research is necessary to find adequate options for including patients’ preferences in an adequate need definition. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that allergy to natural rubber latex (NRL) is associated with cross‐reactivity to certain foods. The aim of this study was to investigate the prevalence of NRL sensitization and allergy in children with atopic dermatitis (n=74). We also examined cross‐reactions between latex and foods, and compared the frequency of suspected latex cross‐reacting fruits in children with and without NRL‐specific immunoglobulin E (IgE). Twelve of the 74 atopic children studied (16.2%; 95% confidence interval (CI), 8.7–26.6%) had circulating IgE antibodies to latex. These NRL‐sensitized children were older and they showed significantly higher total IgE values (p<0.003) when compared with the group of children without NRL sensitization. Of the specific food IgE evaluations, 18.4% (93 out of 505) were positive, and 69.9% were observed in the group of children with latex‐specific IgE, most frequently to potato, tomato, sweet pepper, and avocado. An isolated latex‐specific IgE response without food‐specific IgE was never observed. Exclusively in the latex‐positive group, conformity with the report of allergic symptoms after ingestion of food and increased food‐specific IgE was found. Twenty children without proven latex sensitization showed increased food‐specific IgE, most frequently to potato, banana, and chestnut. Avocado‐specific IgE was never determined in this patient group. No significant differences were detected concerning the sensitization to potato, banana, and kiwi between NRL‐sensitized children and the group of 20 children without latex‐specific IgE. The competitive CAP inhibition using sera from children with specific IgE to both latex and food showed different cross‐reactivities between latex and the specific food. A close relationship existed between latex and avocado (median inhibition: 100%), whereas sensitization to latex... [ABSTRACT FROM AUTHOR]

Recent studies demonstrate reduced interferon-gamma (IFN-γ) secretion in neonates who became atopic later in life. The underlying pathomechanism is still unknown. We therefore examined the effects of bacterial products on neonatal IFN-γ production acting through different T-cell- or antigen- presenting-cell (APC)-stimulating mechanisms: cord-blood mononuclear cells (CBMC) were incubated with lipopolysaccharide (LPS), staphylococcal enterotoxin E (SEE), or a combination of both and restimulated with PMA and ionomycin. LPS and SEE as single stimuli induced IFN-γ production to the same extent in CBMC of neonates with high and low risk of atopy. In contrast, a combination of LPS and SEE had a multiplying effect on IFN-γ secretion only in CBMC of neonates with low risk of atopy. Phenotype analysis revealed that only memory T cells showed impaired IFN-γ synthesis (median 3.6% IFN-γ-producing cells vs 14.2% in controls; P < 0.01), whereas IFN-γ production by naive T cells did not differ in either group. Taken together, these results point to the existence of a disturbed function of costimulatory mechanisms in neonates at high risk of atopy, provoking reduced memory T-cell IFN-γ production. [ABSTRACT FROM AUTHOR]

Formaldehyde (FA), a common indoor air pollutant, has been associated with increased prevalence rates of asthmatic symptoms among exposed individuals in epidemiologic surveys. We studied the influence of FA exposure on inhalative allergic sensitization in the guinea pig. Three groups of guinea pigs (n = 12 each) were exposed to clean air or two different FA concentrations (0.13 and 0.25 ppm) over 5 consecutive days. Exposure was followed by inhalation of 0.5% ovalbumin (OA) as sensitizing allergen. Three weeks later, specific bronchial provocation with OA was performed with body plethysmographic measurement of compressed air (CA). Furthermore, specific anti-OA-IgGl (reaginic) antibodies were determined in serum. In a further six animals, the respiratory tract was examined histologically for signs of inflammation directly after the end of FA or clean air exposure. In the group exposed to 0.25 ppm FA, 10/12 animals were found to be sensitized to OA (positive reaction on specific provocation) vs. 3/12 animals in the control group (P < 0.01). Furthermore, CA measurements of specific bronchial provocation and serum anti-OA-antibodies were significantly higher in the 0.25 ppm FA group than in controls (CA 0.35 vs. 0.09 ml median, P<0.01; anti-OA-IgGl 13 vs. <10 EU median, P<0.05), indicating enhanced sensitization. In the group exposed to 0.13 ppm FA, no significant difference was found compared to the control group. There was no sign of inflammation of the lower airways in FA-exposed guinea pigs other than mucosal edema, which was discovered by morphometry. We conclude that short-term exposure to a low concentration of FA (0.25 ppm) can significantly enhance sensitization to inhaled allergens in the guinea pig. [ABSTRACT FROM AUTHOR]

To assess the relation among eosinophil-related variables in the peripheral blood, bronchial hyperreactivity, and the presence of atopic dermatitis in children aged 5-14 years, we studied 11 patients with atopic dermatitis alone, six with asthma and atopic dermatitis, 12 with asthma alone, and 12 healthy controls. Eosinophil counts, levels of eosinophil cationic protein, and the capacity of eosinophils to generate leukotriene (LT) C4, as well as bronchial hyperreactivity and a severity score for atopic dermatitis, were determined. Eosinophil variables were significantly higher in both patient groups with atopic dermatitis than in normal controls. In particular, ionophore A 23187 LTC4 generation was higher in patients with atopic dermatitis alone (median 82, range 25-273 ng/106 cells) and patients with combined asthma and atopic dermatitis (median 68, range 32-583 ng/106 cells) than in normal controls (median 9, range 1-67 ng/106 cells). However, there was no difference between the group of atopic dermatitis patients with asthma and without asthma. We conclude that eosinophil variables in the peripheral blood are mainly influenced by the presence of atopic dermatitis, and not the presence and the severity of asthma in patients with both asthma and atopic dermatitis. [ABSTRACT FROM AUTHOR]

Salivary SIgA antibodies against RS virus were studied in 105 children during the first year of life. The infants were divided into groups according to their risk of atopy. At birth 13 neonates showed measurable amounts of SIgA to RS virus. In another 26 children specific antibodies were detected but in concentrations too low for quantitative analysis. During the first year of life this increased to 29 antibody-positive Samples with measurable amounts of antibody and 39 with concentrations too low for quantitative determination. At this time 8 children of the high risk group had developed symptoms of allergy. None of these children had measurable amounts of SIgA anti-RSV in their saliva. In comparison, 10 of the remaining 26 high risk infants without symptoms of allergy did have such antibodies. Atopic infants had significantly more respiratory infections during the first year of life than nonatopic infants. The avidity of SIgA anti-RSV in neonatal samples was significantly higher than avidity determined in breast milk SIgA but comparable to the avidity of serum IgG. During the first year of life a continuing decrease of salivary SIgA avidity was observed. [ABSTRACT FROM AUTHOR]

Elevation of salivary SIgA-anti-casein has been shown to occur in newborn infants at risk of allergy. The present study was designed to follow 158 infants over 3 years to relate the onset of clinical disease to SIgA levels at birth. Newborn infants were divided into 3 groups according to their risk of allergy: Group I, (n = 62; no allergy risk); Group 11, (n = 30; low allergy risk); Group 111 (n = 66; high risk group). The groups were matched for smoking, social background, sex, and dietary habits of the patients. SIgA-anti-casein was determined by a direct ELISA. During the first year 59 infants developed atopic diseases (n = 37 of Groups I and 11; II = 22 of Group 111). After 3 years 37/61 infants of the high risk group had developed allergic symptoms. The frequency of atopic disease correlated with increased salivary antibody titers at birth (p < 0.05). 54% of infants with antibody titers > 250 EU/ml developed atopic symptoms at 1 year, 76% high risk infants with this titer developed atopic symptoms at 3 years of age. This study provides evidence that elevation of SIgA-anti-casein at birth not only reflects atopic risk as defined by cord blood IgE or family history, but correlates with the actual development of allergic disease during the first 3 years of life. [ABSTRACT FROM AUTHOR]

Passive smoking has been shown to cause increased incidence of lower respiratory tract infection and wheezing in young children and an inceased risk of childhood asthma. To evaluate possible influence of tobacco smoke on allergic bronchial sensitization we exposed guinea pigs to tobacco smoke in 3 concentrations of clean air (control group) for 8 h on 5 consecutive days (median plasma cotinine 5.0-25.4-87.2 ng/l). The animals were sensitized by repeated inhalation with ovalbumin. Histologic examination at the end of exposure revealed reactive epithelial hyperplasia and regenerative changes as well as inflammatory reaction mainly in the lung periphery, and histamine provocation showed increased bronchial reactivity at the end of tobacco smoke exposure. Sensitization was measured by specific bronchial provocation testing using body plethysmographic measurement of compressed air (CA) and specific anti-ovalbumin-antibodies of the IgGM1-subclass in the serum, measured by direct ELISA in ELISA units (EU). The group with the highest tobacco smoke exposure differed significantly in bronchial reactivity on specific bronchial provocation tests (p <0.005) compared with the control groups and showed elevated unspecific IgG1-antibody levels indicating enhanced sensitization. We conclude that intensive exposure to tobacco smoke over a short period of 5 d can enhance inhalational allergic sensitization in the guinea pig and might explain the increased incidence of respiratory allergies in child passive smokers. [ABSTRACT FROM AUTHOR]

Background Viral respiratory tract infections have been previously considered to be associated with induction of allergic sensitization. Objective and Methods In order to investigate this relationship in an animal model, guinea-pigs were inoculated intranasally with Parainfluenza-3-(PI-3) virus (n = 16) or virus-free culture medium (controls, n = 12), sensitized at day 4 with inhaled ovalbumin (OA) and challenged 3 weeks later with inhaled OA using specific bronchial provocation testing with body plethysmographic measurement of compressed air (CA). Furthermore, specific anti-OA-IgG1-antibodies in serum before challenge were determined by enzyme linked immunosorbent assay ( ELISA). For investigation of airway epithelium permeability horseradish peroxidase (HRP) was inhaled at day 4 after inoculation by six animals, and HRP serum concentrations were determined by a direct ELISA 30 min after inhalation. Results PI-3 infected animals were found to be significantly more sensitized to OA compared with controls, with higher CA values (P< 0.001) on specific bronchial provocation and with increased specific anti-OA-IgG1 titers. Serum-HRP concentrations were about 20 times higher in the infected animals compared with controls. PI-3 infected and sham-infected animals had comparable bronchial reactions on specific provocation with OA when sensitized systemically. Conclusions We conclude that viral respiratory tract infection with PI-3 virus enhances inhalative allergic sensitization in the guinea-pig. Increased mucosal permeability to antigens may be an important pathophysiological mechanism. [ABSTRACT FROM AUTHOR]

Two boys, aged three and seven years with immune thrombocytopenic purpura continued to show platelet counts below 20,000/mm³ inspite of treatment with high dose gammaglobulin and steroids. Alpha-2b-interferon injections were followed by normalisation of platelet counts in both patients. No side effects were seen. Alpha-interferon may be a safe and effective treatment for childhood-ITP. [ABSTRACT FROM AUTHOR]

Regarding declining resources epidemiological data on needs for oral rehabilitation are required. Within the framework of an oral health survey a non-stratified two-stage random sample was taken to represent the over 14-year-old population of Saxony/Germany. The participation rate was 55%. Normative need was determined by dental assessment and guidelines developed in a consensus process, subjective prosthetic treatment need by self-complete questionnaire. About 97% of the realized sample could be planned within the guidelines. About 81% had normative prosthetic treatment need. Compared with the rate of normative need the rate of subjective need (13%) was considerably lower (χ2P < 001). Different predictive parameters of subjective need were identified by logistic regression. Besides other factors subjective need was associated with giving dentist’s recommendation as significant reason for prosthetic restorations [odds ratio (OR)=543], not believing that the own teeth were all right (OR=017), and the existence of prosthetic restorations (OR=387 for fixed restorations; OR=405 for removable dentures). The guidelines proved their suitability to assess normative prosthetic treatment need in oral health surveys. Further research is necessary to find adequate options for including patients’ preferences in an adequate need definition. [ABSTRACT FROM AUTHOR]

Background & Aims: Hydrophobic bile salts such as glycochenodeoxycholate (GCDC) accumulate in cholestatic liver disease and induce hepatocellular apoptosis, promoting profibrotic signalling. The tissue microenvironment is an integral player in cellular pathophysiology, but it is not routinely incorporated into laboratory studies. Tissue oxygen partial pressure (pO₂) may be an underestimated component of the microenvironment: in the liver, a pO₂ of 30-45 mmHg (approximately 6% O₂) is physiological, because of predominant portal blood supply. It was the aim of this project to investigate the impact of physiological hypoxia (i.e. 6% O₂) on hepatocellular function, namely, bile salt-induced apoptosis., Methods: Human hepatoma cells (HepG2-Ntcp) and primary rat hepatocytes were cultured at standard laboratory (hyperoxic) conditions (21% O₂) and at physiological hypoxia (6% O₂) in parallel for 1-8 days to study hepatocellular apoptosis and activation of signalling pathways. Standard laboratory analyses were applied for bile salt uptake, caspase-3/-7 activity, western blotting and gene-array analysis., Results: Culturing at physiological hypoxia protected both human and rat hepatocytes against GCDC-induced apoptosis: caspase-3/-7 activation was diminished by 3.1 ± 0.5-fold in human HepG2-Ntcp and completely abolished in primary rat hepatocytes. Bile salt uptake was unaffected. Induction of hypoxia-inducible factor-1α indicated adaption to physiological hypoxia. The MEK/ERK cascade was activated and anti-apoptotic mediators were induced: N-Myc down-regulated gene, gelsolin and carbonic anhydrase IX were upregulated 12.4-, 6.5- and 5.2-fold respectively., Conclusions: We conclude from these data that (i) physiological hypoxia protects hepatocytes from bile salt-induced apoptosis, (ii) tissue pO₂ is a crucial, underestimated component of the microenvironment and should (iii) be considered when studying hepatocellular physiology in vitro., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Primary liver tumours are very rare in the neonatal period. Differential diagnoses include haemangioendothelioma, malignant hepatoblastoma and mesenchymal hamartoma. Due to non-specific clinical symptoms and indecisive imaging findings, correct diagnosis may be difficult to establish. We report a female preterm newborn who was delivered at 33 weeks of gestation and in whom ultrasonography (US) revealed a large cystic intraabdominal tumour of unknown origin. For further evaluation, contrast-enhanced multidetector computed tomography (CT) was performed on the 4th day of life using a low-dose protocol (80 kVp, 50 mAs, collimation 0.75 mm, total effective dose 3.6 mSv). Based on CT findings, diagnosis of an intrahepatic mesenchymal hamartoma was made and confirmed by tumour resection and histopathological examination. In conclusion, multidetector CT (MDCT) using a low-dose protocol can be exceptionally used to establish diagnosis of a mesenchymal hamartoma in a preterm newborn.

Background: This analysis was based on an oral health survey with dental examination and interview by questionnaire., Method: The data set comprised a representative random sample of the over 14-year-old residents of the German Federal State of Saxony (n=714), in which a multivariate logistic regression analysis was conducted. The dependent variable was the debris index (DI) score of the oral hygiene index scoring system. The subjects were split into 2 groups by dividing DI scores into tertiles: those with acceptable oral hygiene (1st tertile, DI 0.00< or =1.20) and unacceptable oral hygiene (2nd and 3rd tertile, DI>1.20). The most important explanatory variable was the community periodontal index of treatment need (CPITN)., Results: The higher the CPITN score, the lower the probability of acceptable oral hygiene. In relation to the reference category score 0, higher CPITN scores were associated with acceptable oral hygiene, with an odds ratio 0.05 (95% confidence interval (CI)=0.01-0.23) for CPITN score 1, and an odds ratio 0.02 (95% CI: 0.01-0.08) for score 4. Further significant variables were: self-evaluation of tooth condition, gender, and the number of missing teeth.

To assess the relation among eosinophil-related variables in the peripheral blood, bronchial hyperreactivity, and the presence of atopic dermatitis in children aged 5-14 years, we studied 11 patients with atopic dermatitis alone, six with asthma and atopic dermatitis, 12 with asthma alone, and 12 healthy controls. Eosinophil counts, levels of eosinophil cationic protein, and the capacity of eosinophils to generate leukotriene (LT) C4, as well as bronchial hyperreactivity and a severity score for atopic dermatitis, were determined. Eosinophil variables were significantly higher in both patient groups with atopic dermatitis than in normal controls. In particular, ionophore A 23187 LTC4 generation was higher in patients with atopic dermatitis alone (median 82, range 25-273 ng/10(6) cells) and patients with combined asthma and atopic dermatitis (median 68, range 32-583 ng/10(6) cells) than in normal controls (median 9, range 1-67 ng/10(6) cells). However, there was no difference between the group of atopic dermatitis patients with asthma and without asthma. We conclude that eosinophil variables in the peripheral blood are mainly influenced by the presence of atopic dermatitis, and not the presence and the severity of asthma in patients with both asthma and atopic dermatitis.

Granulocytes from 23 asthmatic children aged 4-15 years and 32 age-matched healthy children were studied. Cells were purified by Dextran sedimentation and Percoll gradient centrifugation from heparinized blood. After in vitro stimulation by ionophore A23187 the amount of newly synthesized PAF and LTC4 was assessed by radio receptor assay or radioimmunoassay respectively. Eight patients had symptoms of asthma within the last 3 weeks before examination. Granulocytes from the symptomatic patients showed a significantly higher PAF generation (median 125 ng/10(6) cells, range 7-189 ng/10(6) cells) when compared to asymptomatic patients (p less than 0.001, median 14 ng/10(6) cells, range 6-33 ng/10(6) cells) or controls (p less than 0.001, median 11 ng/10(6) cells, range 3-26 ng/10(6) cells). In contrast, LTC4 generation was increased in both patient groups. The results suggest a regulatory role of PAF in the exacerbation of asthma.