Systemic sclerostin antibody treatment increases osseointegration and biomechanical competence of zoledronic-acid-coated dental implants in a rat osteoporosis model.

Osseointegration of dental implants can be promoted by implant-surface modifications using bisphosphonate coatings. In addition, it is of clinical interest to promote peri-implant bone formation and to restore bony structure in low bone-mass patients. The present study evaluated a combination of an anti-resorptive zoledronic acid (ZOL) implant-coating and a systemically applied sclerostin antibody, a known bone anabolic treatment principle, versus sole sclerostin antibody treatment or ZOL implant-coating in a rat osteoporosis model. Uncoated reference surface implants or ZOL-coated implants (n = 64/group) were inserted into the proximal tibia of aged osteoporotic rats three months following ovariectomy. 32 animals of each group received once weekly sclerostin antibody therapy. Osseointegration was assessed 2 or 4 weeks post-implantation by ex vivo µCT, histology and biomechanical testing. Overall implant survival rate was 97 %. Histomorphology revealed pronounced bone formation along the entire implant length of ZOL-coated implants. At 4 weeks following implant insertion, bone-implant contact, cancellous bone mineral density and bone volume/tissue volume were significantly increased for the combination of ZOL and sclerostin antibody as compared to sclerostin antibody or ZOL implant-coating alone. Removal torque was also significantly increased in the combination therapy group relative to animals receiving only sclerostin antibody therapy or ZOL-coated implants. In an osteoporotic rat model, the combination of anti-resorptive ZOL implant-coating and systemically applied sclerostin antibody led to significantly increased peri-implant bone formation. Therefore, the combination of ZOL and the osteoanabolic sclerostin antibody was more effective than either agent alone.

Pregnancy and perinatal conditions and atopic disease prevalence in childhood and adulthood.

BACKGROUND: Previous studies showed controversial results for the influence of pregnancy-related and perinatal factors on subsequent respiratory and atopic diseases in children. The aim of this study was to assess the association between perinatal variables and the prevalence of asthma, bronchial hyperreactivity (BHR), flexural eczema (FE), allergic rhinitis, and sensitization in childhood and early adulthood. METHODS: The studied population was first examined in Munich and Dresden in 1995/1996 at age 9-11 years. Participants were followed until age 19-24 years using questionnaires and clinical examinations. Associations between perinatal data and subsequent atopic diseases were examined using logistic regression analyses adjusting for potential confounders. RESULTS: Cesarean section was statistically significantly associated with BHR in early adulthood (odds ratio 4.8 [95% confidence interval 1.5-15.2]), while assisted birth was associated with presence of asthma symptoms in childhood (2.2 [1.2-3.9]), FE symptoms (2.2 [1.2-4.3]) and doctor's diagnosis of atopic dermatitis (1.9 [1.0-3.4]) in childhood, and sensitization in early adulthood (2.2 [1.1-4.3]). Lower birth length (1.9 [1.1-3.2]), lower birthweight (0.5 [0.3-0.9]), and higher birthweight (0.6 [0.4-1.0]) were predictive of sensitization in early adulthood compared to average birth length and birthweight, respectively. None of the other perinatal factors showed statistically significant associations with the outcomes. CONCLUSIONS: Our results indicate that children who are born by cesarean section and especially by assisted birth, might be at greater risk for developing asthma, FE, and sensitization and should hence be monitored. Prenatal maternal stress might partly explain these associations, which should be further investigated.

Unexpectedly high incidences of chronic non-bacterial as compared to bacterial osteomyelitis in children.

Historically, osteomyelitis was considered an infectious disorder. More recently, inflammatory mechanisms were recognized causing a significant proportion of pediatric osteomyelitis. This study was to compare characteristics of children with chronic non-bacterial (CNO) and bacterial osteomyelitis (BOM). A chart review of osteomyelitis patients from the departments of pediatrics, pediatric surgery, orthopedic surgery, and oral and maxillofacial surgery was conducted in a tertiary referral center, covering the years 2004-2014. Institutional incidences of CNO (n = 49) and BOM (n = 56) were comparable. Differentiation between CNO and BOM based on clinical or laboratory findings was mostly impossible. However, children with BOM more frequently presented with local inflammatory signs (47 vs. 68 %, p = 0.040), fever (12 vs. 38 %, p = 0.003), and abscesses (0 vs. 39 %, p < 0.001). Peripheral arthritis (14 vs. 0 %, p < 0.001), inflammatory bowel disease (10 vs. 2 %, p = ns), and hyperostosis (29 vs. 4 %, p = 0.001) were more common in CNO. Whole-body MRI was performed in 76 % of CNO patients, unveiling multifocal lesions in 80 % (CRMO). Though considered a rare disorder, institutional incidences of CNO were comparable to BOM, and the discrimination between CNO and BOM solely based on clinical aspects was mostly impossible. This is of special interest, since a correct and timely diagnosis is of utmost importance for long-term outcomes in both disorders. Whole-body MRIs should be considered in chronic osteomyelitis to (1) detect clinically inapparent lesions in CNO and (2) indirectly exclude (usually unifocal) chronic bacterial infections. Prospective studies are warranted to establish evidence-based diagnostic and therapeutic approaches to CNO.

Osseointegration of biochemically modified implants in an osteoporosis rodent model.

The present study examined the impact of implant surface modifications on osseointegration in an osteoporotic rodent model. Sandblasted, acid-etched titanium implants were either used directly (control) or were further modified by surface conditioning with NaOH or by coating with one of the following active agents: collagen/chondroitin sulphate, simvastatin, or zoledronic acid. Control and modified implants were inserted into the proximal tibia of aged ovariectomised (OVX) osteoporotic rats (n = 32/group). In addition, aged oestrogen competent animals received either control or NaOH conditioned implants. Animals were sacrificed 2 and 4 weeks post-implantation. The excised tibiae were utilised for biomechanical and morphometric readouts (n = 8/group/readout). Biomechanical testing revealed at both time points dramatically reduced osseointegration in the tibia of oestrogen deprived osteoporotic animals compared to intact controls irrespective of NaOH exposure. Consistently, histomorphometric and microCT analyses demonstrated diminished bone-implant contact (BIC), peri-implant bone area (BA), bone volume/tissue volume (BV/TV) and bone-mineral density (BMD) in OVX animals. Surface coating with collagen/chondroitin sulphate had no detectable impact on osseointegration. Interestingly, statin coating resulted in a transient increase in BIC 2 weeks post-implantation; which, however, did not correspond to improvement of biomechanical readouts. Local exposure to zoledronic acid increased BIC, BA, BV/TV and BMD at 4 weeks. Yet this translated only into a non-significant improvement of biomechanical properties. In conclusion, this study presents a rodent model mimicking severely osteoporotic bone. Contrary to the other bioactive agents, locally released zoledronic acid had a positive impact on osseointegration albeit to a lesser extent than reported in less challenging models.

The randomized shortened dental arch study: tooth loss over five years.

OBJECTIVES: The study was designed to provide clinical outcome data for two treatments of the shortened dental arch (SDA). MATERIAL AND METHODS: In a multicenter randomized controlled clinical trial, patients with complete molar loss in one jaw were provided with either a partial removable dental prosthesis (PRDP) retained with precision attachments or treated according to the SDA concept preserving or restoring a premolar occlusion. No implants were placed. The primary outcome was tooth loss. RESULTS: Of 152 treated patients, 132 patients reached the 5-year examination. Over 5 years, 38 patients experienced tooth loss. For the primary outcome tooth loss, the Kaplan-Meier survival rates at 5 years were 0.74 (95% CI 0.64, 0.84) in the PRDP group and 0.74 (95% CI 0.63, 0.85) in the SDA group. For tooth loss in the study jaw, the survival rates at 5 years were 0.88 (95% CI 0.80, 0.95) in the PRDP group and 0.84 (95% CI 0.74, 0.93) in the SDA group. The differences were not significant. No Cox regression models of appropriate fit explaining tooth loss on the patient level could be found. CONCLUSIONS: The overall treatment goals of a sustainable oral rehabilitation and the avoidance of further tooth loss over longer periods were not reliably achievable. The influence of the type of prosthetic treatment on tooth loss might have been overestimated. CLINICAL RELEVANCE: Regarding our results, the patient's view will gain even more importance in the clinical decision between removable and fixed restorations in SDAs.

IL10 promoter polymorphisms are associated with systemic onset juvenile idiopathic arthritis (SoJIA).

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a rare, but severe cause of childhood disability. Systemic onset JIA (SoJIA) accounts for approximately 5.8% of all JIA cases and is associated with cytokine dysregulation, including interleukin (IL-)1, IL-6 and tumour necrosis factor (TNF-)α. IL-10 is an immuno-regulatory cytokine, which in part regulates inflammation by controlling inflammatory cytokine expression. Dysregulation in IL-10 expression and certain single nucleotide polymorphisms (SNPs) in the IL-10 promoter were shown to be associated with autoimmune and infectious diseases. METHODS: Genomic DNA-samples from SoJIA patients from two German Paediatric Rheumatology centres, and healthy controls were analysed for three well defined IL-10 promoter SNPs (-1082G>A, -819C>T, and -592C>A). These SNPs are in tight linkage disequilibrium, and result in three predominant (or 'classical') haplotypes: ATA, ACC, and GCC. ATA and ACC are associated with low and medium, GCC is associated with high IL-10 expression. RESULTS: Here, we show a strong association of IL-10 promoter polymorphisms with SoJIA. We demonstrate a significantly increased frequency of low IL-10 expressing -1082A/A alleles, the medium IL-10 expressing ACC haplotype (p=0.01), and an enrichment of the rare GTC haplotype (p<0.001) in patients with SoJIA. Heterozygous -1082G/A alleles (p<0.001), and the GCC haplotype (p<0.001) on one allele protect from developing SoJIA. CONCLUSIONS: This suggests a central role of the immuno-regulatory cytokine IL-10 in the pathogenesis of SoJIA.

[Statistical analysis of correlated measurement data in ophthalmology : Tutorial for the application of the linear mixed model in SPSS and R using corneal biomechanical parameters]. / Statistische Auswertung korrelierter Messdaten in der Augenheilkunde : Tutorial zur Verwendung des linear gemischten Modells in SPSS und R anhand biomechanischer Parameter der Hornhaut.

BACKGROUND: In ophthalmology data from both eyes of a person are frequently included in statistical analyses. As correlated data are used this procedure contradicts the independency principle for classical statistical tests, such as Student's t­test and analysis of variance (ANOVA). In this tutorial a new possibility is presented in which data from both eyes can be used for statistical analysis. OBJECTIVE: The statistical approach of linear mixed models (LMM) was used to take correlated data of both eyes of patients into account. METHODS: The LMM is available in several statistical software packages, e.g. SPSS and R, and allows the inclusion of measurement data from both eyes of a person in the statistical analysis. The application was tested on data from a biomechanical characterization of the cornea from healthy participants assessed with the dynamic Scheimpflug analyzer (Corvis ST; Oculus, Wetzlar, Germany). RESULTS: A total of 158 eyes from 79 healthy participants were included. A strong correlation between the right and left eyes of the participants could be observed with respect to the analyzed parameters. Comparison of the biomechanical parameters between the different age groups showed that P-values were increased when using the LMM compared to the ANOVA. Older participants (56-79 years) showed a significantly shorter time to the second applanation (P = 0.002), a significantly increased eyeball movement during the deformation (P = 0.001) and a significantly higher stiffness at the first applanation (P = 0.006) compared to younger participants (18-35 years). CONCLUSION: The analysis of measurement data from both eyes using classical statistical tests, without the consideration of the correlation, leads to an overestimation of the statistical power. This can be avoided by implementation of the LMM.

The synovitis of "non-inflammatory" orthopaedic arthropathies: a quantitative histological and immunohistochemical analysis.

OBJECTIVE: To quantify inflammatory changes in synovial membranes from orthopaedic "non-inflammatory" arthropathies (Orth. A). METHODS: Synovial membranes from patients with femur fracture, avascular necrosis of the femur, plica syndrome, and meniscus and/or ligament injury (n = 23); rheumatoid arthritis (n = 28); osteoarthritis (OA; n = 25); and from normal controls (n = 10) were assessed by light microscopy, a histological synovitis score, immunostaining for CD3, CD20, CD38, CD68, Ki-67 and von Willebrand factor, and with an immunohistochemical inflammation score. RESULTS: Orth. A histology varied between normal and markedly inflamed. Predominant abnormalities were mild lining hyperplasia, scattered inflammatory cells and small perivascular infiltrates. The synovitis score classified Orth. A as "mild synovitis". Inflammatory cells occurred frequently: CD68+ cells in 100% of Orth. A specimens; CD3+, 91%; CD38+, 70%; and CD20+, 39%. Orth. A had 36% greater lining thickness (p = 0.04), 40% higher vascular density (p = 0.009) and 51.3-fold higher CD38+ cell density (p = 0.02) than normal controls; and 60% fewer subintimal Ki-67+ cells (p = 0.003), 42% fewer CD68+ lining cells (p<0.01) and 40% fewer subintimal CD68+ cells (p<0.01) than OA. The immunohistochemical inflammation score was 2.2-fold higher in Orth. A than in controls (p = 0.048) and similar to OA, with three Orth. A specimens showing marked inflammation. CONCLUSIONS: Synovial membranes from "non-inflammatory" arthropathies featured neovascularisation and inflammation intermediate between normal and OA synovium. These results expand previous findings that mechanical joint injury may lead to a mild-to-moderate synovitis.

Reduction of postoperative lymphedema after oral tumor surgery with sodium selenite.

The objective of this double-blind, randomized study was to establish whether sodium selenite administered orally or intravenously reduces postoperative lymphedema after oral tumor surgery and to study the effect of sodium selenite on glutathione peroxidase (GPX) activity and oxygen radical production. Twenty patients were enrolled in the study. Each of the participants received 1,000 microg sodium selenite intravenously or orally daily for 3 wk during the pre-, intra-, and postoperative period. The extent of lymphedema was measured for 2 wk and the plasma and whole-blood selenium concentration, GPX, reactive oxygen species (ROS), NO, and malonic dialdehyde were measured for 1 yr postoperatively. There was an inverse correlation between the severity of the lymphedema and the whole-blood/plasma selenium concentration and GPX activity. In addition, a positive correlation between the ROS concentration and the extent of lymphedema was observed. A significant reduction of lymphedema occurred in the sodium selenite-treated group. It is concluded that sodium selenite represents a suitable adjuvant treatment of secondary lymphedema in surgically treated patients with tumors in the oral and maxillofacial areas. Treatment with sodium selenite is especially advantageous as it can be instituted immediately after surgery prior to wound healing when manual lymphatic decongestion therapy cannot be applied.

MRI and dental implantology: two which do not exclude each other.

Currently, histological techniques are used to analyse implant-tissue-interactions. However, these methods are destructive and time-consuming. Furthermore, they require a large number of animals as longitudinal observations in one individual are not possible. The evaluation by non-destructive imaging techniques provides the opportunity to study the osseous integration with a reduced number of animals and a decreased biological variability. The present study examined the suitability of magnetic resonance imaging (MRI) to assess peri-implant bone formation exemplarily for a dental implant in a minipig model. Due to its compatibility to MR imaging polyetheretherketone (PEEK) coated with a thin layer of titanium was applied as implant material. Osseointegration was analysed within different peri-implant regions quantifying bone volume density and soft tissue content, which were assessed by MRI and histology, likewise. It could be proven that the examined regions showed differences in bone formation; the region adjacent to the implant apex turned out to be the most dynamic. Both methods led to comparable results with no significant differences regarding to the assessed parameters. Moreover, it was demonstrated that titanium coated PEEK showed a sufficient osseointegration and MRI provides a promising application in monitoring bone formation.

Flow cytometric DNA-quantification of three-color immunophenotyped cells for subpopulation specific determination of aneuploidy and proliferation.

A method is described for three-color immunophenotyping and simultaneous DNA-quantification using a flow cytometer equipped with a 488-nm argon laser and a mercury lamp (UV). The approach includes reproducible immunophenotyping comparing antigen expression before and after cell manipulation for DNA-measurement. The coefficients of variation after DNA-staining (CV=3.13 for T-cells in peripheral blood and CV=3.38 for T-cells in bone marrow) were adequate for exact DNA-analysis. For aneuploidy detection, a true internal standard was established measuring, for example, the DNA-content of T-cells in B-cell disease simultaneously with the DNA-content of the malignant cells. Using this method, aneuploidies could be unequivocally detected in 17 out of 24 patients with multiple myeloma. Furthermore, intratumor heterogeneities in DNA-content and antigen expression could be recognized, allowing an exact separation of tumor cells and normal hematopoiesis. The study also demonstrated the importance of exact immunophenotypic characterization of lymphocyte subpopulations and the determination of their specific proliferation, for example after proliferation induction in cell cultures. Future studies should address the applicability of this rather simple multiparameter approach for simultaneous immunophenotyping and DNA-measurement especially in the detection of minimal amounts of aneuploid cells after chemotherapy.

DNA cytophotometry and prognosis in typical and atypical bronchopulmonary carcinoids. A clinicomorphologic study of 100 neuroendocrine lung tumors.

Surgical material obtained from 100 patients with typical carcinoids (TC) and atypical carcinoids (AC) of the lung (including 100 primary, four residual tumors, and four lymph node or distant metastases) was investigated by conventional histology and scanning DNA cytophotometry. Of the 60 TC (96%), 58 exhibited euploid DNA histograms compared with only 20 (50%) of the 40 AC. The morphologic findings were related to the patients' survival (median observation period, 9 years). Statistical analyses disclosed the histologic type of disease (TC versus AC) and the DNA content of tumors (euploid versus aneuploid) to affect prognosis significantly (p < 0.001). Deaths resulting from tumor were exclusively observed among patients with atypical (eight of 40) or DNA aneuploid carcinoids (eight of 22). Six patients were alive with persistent tumor manifestations 3 to 20 years after initial diagnosis, four with DNA diploid primary carcinoids. The presence of lymph node metastases alone was not associated with poor prognosis as long as the primary tumor or the related metastases showed a diploid DNA content. DNA cytophotometry thus might be regarded as an adjunctive prognostic criterion in individual carcinoid cases.

Flow cytometric DNA quantification in immunophenotyped cells as a sensitive method for determination of aneuploid multiple myeloma cells in peripheral blood stem cell harvests and bone marrow after therapy.

The simultaneous measurement of DNA content and myeloma-related antigens (B-B4 or CD38) by flow cytometry is proposed as a method for the detection of aneuploid plasma cells in peripheral blood stem cell (PBSC) harvests and in bone marrow after therapy. In 30 patients with initially detected aneuploid myeloma cells we evaluated the bone marrow after therapy and in eight of these patients 23 PBSC harvests were analyzed. In 13 of 23 PBSC harvests aneuploid myeloma cells were detectable (range: 0.02-0.63%). In the bone marrow of the 30 patients aneuploid plasma cells were detectable in all samples after chemotherapy (range: 0.12-35.70%) and after autologous PBSC transplantation in two of three patients (0.21% and 0.03%). Furthermore the relationship between diploid and aneuploid plasma cells can be evaluated. In the PBSC harvests the percentage of aneuploid plasma cells is significantly lower than that of diploid plasma cells (P=0.006). In contrast, in bone marrow the aneuploid plasma cells are predominant in most patients even after therapy (24 of 30 patients; P=0.0055). In the case of initially detected aneuploid myeloma cells, a contamination with malignant cells can be estimated with a simple flow cytometric method in PBSC harvests and in bone marrow after therapy.

The incidence of DNA aneuploidy in multiple myeloma does not correlate with stage of disease.

The bone marrow of 47 patients with multiple myeloma (MM), 2 patients with plasma cell leukemia, and 11 patients with monoclonal gammopathy of undetermined significance (MGUS) was analyzed by flow cytometry for the detection of DNA aneuploidy. The question to be addressed was whether a correlation exists between the incidence of DNA aneuploidy and the stage of disease. With one-parameter analysis of DNA staining, a DNA aneuploidy was detectable in 17 of 60 patients. The detection rate for DNA aneuploidies could be increased to 37 of 60 patients with the second method, the simultaneous measurement of DNA content in additional immunophenotyped cells (CD38 or B-B4). In MGUS and the early stages of MM, the discrepancy between both methods was higher than in stage III MM. There were no statistical differences in the incidence of DNA aneuploidy between MGUS or the early stages of MM and stage III MM (21/32 patients vs 16/26 patients). The CD56 expression in plasma cells was significantly higher in cases of DNA aneuploidy (mean +/- SD, 64.7% +/- 33.65% vs 39.3% +/- 36.69%; P = .028). Comparing the ratio of diploid to DNA aneuploid with that of CD56+ to CD56- plasma cells, a correlation was found in MGUS (r = 0.7320) in the early stages of MM, I and II (r = 0.8023), but not in stage III MM. Based on these data, the dual-staining method for DNA content in immunophenotyped cells is preferred for the detection of DNA aneuploidy, especially in the early stages of MM and in MGUS. The clinical importance of a classification of DNA aneuploidy and CD56 antigen expression together is proposed for testing.

Efficacy of tissue engineered bone grafts containing mesenchymal stromal cells for cleft alveolar osteoplasty in a rat model.

UNLABELLED: The development of sufficient tissue engineered bone grafts for alveolar cleft osteoplasty could reduce the necessity of autogenous bone grafts and its donor site morbidity. The aim of the study was to evaluate tissue engineered bone grafts in an artificially created bone defect. Bone grafts were created in vitro colonizing a synthetic hydroxyapatite-tricalciumphosphate scaffold (BONITmatrix(®)) with either undifferentiated mesenchymal stromal cells (group 1) or osteogenic differentiated mesenchymal stromal cells (group 2). Cells were multiplied from bone marrow of donor rats. Unmodified scaffolds (group 3) and the tissue engineered bone grafts were inserted into artificial maxillary defects of 54 Lewis rats. In 18 animals the defects remained unfilled (control). After one, three and six weeks the rats were sacrificed. The defect was evaluated radiologically and histologically with regard to the remaining defect volume and diameter. Statistical analysis followed. The bone grafts led to a specific bone formation at the defect margin. No complete reunion of any defect was observed within the healing time. After six weeks, the remaining defect volume was 6.86 ± 3.21 mm(3) (control), 4.08 ± 1.36 mm(3) (group 1), 5.00 ± 0.84 mm(3) (group 2) 5.50 ± 1.05 mm(3) (group 3). The remaining defect diameter measured 2.63 ± 0.52 mm (control), 2.39 ± 0.23 mm (group 1), 2.53 ± 0.22 mm (group 2) and 2.70 ± 0.66 mm (group 3). In all experimental groups the defect volume and diameter decreased over time, which was significant for group 1 (p = 0.014), group 2 (p = 0.025) and group 3 (p = 0.048). The defect volume and width was significantly reduced for bone grafts containing undifferentiated cells compared to control (p = 0.035) or scaffolds only (p = 0.05). CONCLUSION: Tissue engineered bone grafts induce a pronounced bone formation in artificial bone defects compared to unfilled controls or scaffolds only.

Chondroitin sulfate and sulfated hyaluronan-containing collagen coatings of titanium implants influence peri-implant bone formation in a minipig model.

An improved osseous integration of dental implants in patients with lower bone quality is of particular interest. The aim of this study was to evaluate the effect of artificial extracellular matrix implant coatings on early bone formation. The coatings contained collagen (coll) in conjunction with either chondroitin sulfate (CS) or sulfated hyaluronan (sHya). Thirty-six screw-type, grit-blasted, and acid-etched titanium implants were inserted in the mandible of 6 minipigs. Three surface states were tested: (1) uncoated control (2) coll/CS (3) coll/sHya. After healing periods of 4 and 8 weeks, bone implant contact (BIC), bone volume density (BVD) as well as osteoid related parameters were measured. After 4 weeks, control implants showed a BIC of 44% which was comparable to coll/CS coated implants (48%) and significantly higher compared to coll/sHya coatings (37%, p = 0.012). This difference leveled out after 8 weeks. No significant differences could be detected for BVD values after 4 weeks and all surfaces showed reduced BVD values after 8 weeks. However, at that time, BVD around both, coll/CS (30%, p = 0.029), and coll/sHya (32%, p = 0.015), coatings was significantly higher compared to controls (22%). The osteoid implant contact (OIC) showed no significant differences after 4 weeks. After 8 weeks OIC for controls was comparable to coll/CS, the latter being significantly higher compared to coll/sHya (0.9% vs. 0.4%, p = 0.012). There were no significant differences in osteoid volume density. In summary, implant surface coatings by the chosen organic components of the extracellular matrix showed a certain potential to influence osseointegration in vivo.

Relations between IL-3-induced proliferation and in vitro cytokine secretion of bone marrow cells from AML patients.

The influence of IL-3 on the bone marrow cells of 53 patients with acute myeloid leukaemia (AML) was investigated after 72 h suspension in cultures by analysing the proliferation of blasts and the secretion of cytokines. The titres of IL-1beta IL-6, TNF-alpha and IL-3 were measured in the supernatants of these cultures with ELISA tests. Comparing the percentage of cells in S-phases of control cultures and cultures with IL-3, the leukaemias were divided into two growth pattern groups: IL-3-insensitive (n=19) and IL-3-sensitive (n=34) leukaemias. The IL-3-insensitive AML cells show a greater ability for autonomous growth, first by the increase of S-phase in the control culture compared with the S-phase in vivo (P=0.0486) and second, by the higher constitutive secretion (control culture) of IL-1beta P =0.0004), IL-6 ( P =0.0395) and TNF-alpha P=0.0005). The IL-3-induced secondary cytokine secretion is also different in the two growth pattern groups. Whereas in the IL-3-insensitive AML cells a moderate increase of IL-1beta (1.48-fold increase) was present, in the IL-3-sensitive AML cells a 4.72-fold increase of IL-1beta 2.71-fold increase of IL-6 and 11.81-fold increase of the TNF-alpha titre could be detected. Overall, the data show an inverse correlation between the ability of AML cells to respond to IL-3 with increase of an S-phase and the constitutive secretion of IL-1beta, II-6 and TNF-alpha. A further effect of IL-3 is the induction of secondary cytokine secretion in the bone marrow of IL-3-sensitive growing AML cells.

Prevalence and determinants of house dust mite allergen in East German homes.

BACKGROUND: In 1990/91, allergic sensitization to house dust mites (HDM) and other allergens was more prevalent in children from West Germany than from East Germany. OBJECTIVE: To test the hypothesis that low indoor exposure to HDM allergen in East Germany has contributed to this difference. METHODS: HDM allergen concentrations were determined in 634 East German dwellings shortly after the German reunification. RESULTS: HDM group I allergen (Der p 1 + Der f 1) levels in mattresses (median 2.16, geometric mean 2.07, maximum 278.9 microg/g dust) and carpets (median 0.41, geometric mean 0.48, maximum 96.3 microg/g dust) were within the range of levels determined in West Germany in other studies. One particular East German type of dwelling (light concrete buildings) was associated with lower mite allergen exposure, but only a minority of the population lived there. Coal heating, installed in the majority of dwellings before 1989, was associated with higher allergen exposure. Higher relative humidity (RH) was a main risk factor for higher Der p 1 exposure (odds ratio [OR] for exposure to > 0.05 microg/g dust on carpets: 1.4 [95% confidence interval (CI) 1.2-1.8] for + 10% RH) but not for higher Der f 1 exposure. Higher temperature was associated with a lower risk for elevated Der p 1 levels (> 0.05 microg/g dust on carpets): OR 0.6 (95% CI 0.5-0.8) for + 2 degrees C. CONCLUSION: Mite allergen exposure is not lower in East Germany than in West Germany. The data does not support the hypothesis, that low HDM allergen exposure in East Germany is a cause for the lower prevalence of HDM sensitization in East German children.

[Quality of diabetes management in the free Saxony state--scientific evaluation of the Saxony model for managing diabetes. EVA group]. / Untersuchungen zur Qualität der Diabetikerbetreuung im Freistaat Sachsen--die wissenschaftliche Begleitung des Sächsischen Modells zur Diabetikerversorgung. EVA-Gruppe.

After the societal change in the "New Federal States" of Germany Saxon diabetologists developed an integrated concept for care of diabetic patients: the Saxon Care Model (SCM). It aims at quality assurance in diabetes care and is based on services by cooperating general practitioners and specialists. This model was evaluated. First results were obtained describing the quality of care for 510 patients at baseline. This sample was collected at two specialized diabetologists (level 2), two specialized out-patient units at universities (level 2) and two general practitioners (level 1). The design of the study is a descriptive evaluation. Process and outcome quality at specialized and primary care units working according to the SCM is relatively high. HbA1c measurements were taken in order to quantify outcome quality. The results for primary as well as specialized care units ranged from acceptable to very good. They unfortunately cannot be generalized. The patients expressed that their quality of life was limited only scarcely. The presented preliminary results indicate a high effectiveness of the SCM with regard to relevant process-related outcome-variables. The large variance between single practices of both levels demonstrates that deficits in early diagnosis of diabetes-related complications still exist. On the other hand this points towards resources of quality improvement. The influence of quality assuring measures, e.g. quality circles, will be assessed in a three-year follow up.

Shift of aberrant antigen expression at relapse or at treatment failure in acute leukemia.

The flow cytometric detection of aberrant antigen expression is one method proposed for the quantification of minimal residual disease (MRD) in acute leukemias. The present study was designed to investigate the stability of the aberrant antigen expression at relapse or at treatment failure of initial chemotherapy. For this purpose, multiparameter immunophenotyping with a panel of 15 monoclonal antibodies was used at diagnosis as well as at relapse (43 patients with overall 65 aberrations) and at treatment failure (35 patients with overall 66 aberrations). There was a significant decrease in the percentage of the initially described aberrant antigen expression on leukemia blasts at relapse (P = 0.001; n = 65) as well as at treatment failure (P = 0.0001; n = 66) considering all aberrations in the whole leukemia population. Concerning only patients with acute myelogenous leukemia (AML), significant decreases in the aberrant expression could be detected at relapse (P = 0.031; n = 42) and at treatment failure (P = 0.0001; n = 52). The changes in patients with acute lymphoblastic leukemia (ALL) were significant only at relapse (P = 0.006; n = 23). Initially, the most informative aberration was not detectable in four patients at relapse and in seven patients at treatment failure. A decrease of under 50% of the initial value was observed in another 8 patients at relapse and in 10 patients at treatment failure. In further studies assessing the detection of aberrant antigen expression for MRD, quantification of the relapses should be explicitly analyzed regarding the persistence of the initially described aberrant antigen expression.