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Ohne Zusammenfassung     

The kinetics of immune reconstitution after human marrow transplantation

Human marrow transplantation for the treatment of malignant and nonmalignant disorders is becoming an established modality of therapy. As in any aggressive therapeutic modality, the benefits must be balanced with the risks of the therapy. The aggressive chemoradiotherapy used to prepare patients for marrow transplantation creates a transient immunodeficiency disorder postgrafting until the transferred donor marrow reestablishes a competent immune system. Immune reconstitution posttransplant follows a general pattern developing from immature to mature immune functions. Immune reactivity during the first month postgrafting is extremely low. Cytotoxic and phagocytic functions recover by day 100, while more specialized and cooperative functions of T and B cells remain impaired up to one year or more postgrafting. After the first year postgrafting, the various components of the immune systems of most healthy marrow recipients begin to work synchronously, whereas the immune systems of recipients with chronic graft-v-host disease (GVHD) remain crippled. Recent evidence shows that transfer of specific immunity from marrow donors to marrow recipients plays a role in reestablishing immunocompetence. Transferred antigen-specific immunity may explain why more recipients do not die from overwhelming infections.     

Inadvertent ligation of the left pulmonary artery

In five patients, aged 4 days to 20 months, the left pulmonary artery was inadvertently ligated at the time of attempted closure of the patent ductus arteriosus. The complication was recognized in these patients between 1 day and 5 years later from findings of chest radiography, two-dimensional echocardiography with spectral analysis of Doppler shifted echoes, and angiography. In three patients, the presence of asymmetric pulmonary blood flow on chest radiographs obtained after surgery initially suggested the diagnosis. In the other two patients with bronchopulmonary dysplasia, the diagnosis was made by means of two-dimensional echocardiography and Doppler spectra in one and angiography in the other. On angiograms, the left pulmonary artery distal to the ligation was visualized by delayed opacification from aortic collaterals in three patients and by means of pulmonary venous wedge injection in one. Radiographic and echocardiographic examination with Doppler spectra may permit prompt diagnosis and early correction of this complication.     

Meniscus tears of the knee: prospective evaluation with CT

A total of 209 patients underwent prospective axial computed tomography (CT) examinations of the knee to evaluate the ability of this technique to identify and characterize knee menisci in patients believed to have meniscus tears. Of the 359 knees examined, 105 subsequently underwent arthrography, arthroscopy, or arthrography and arthroscopic surgery. In this group, the sensitivity of CT was 88.5%, specificity was 95.5%, and accuracy was 91.5%. Although axial CT is a sensitive and effective method for the detection and characterization of tears involving the medial and lateral menisci, purely horizontal or nondisplaced peripheral tears may be difficult to demonstrate.     

Keine irreführende wettbewerbswidrige Werbung eines Medizinischen Versorgungszentrums mit der Bezeichnung “Rheumazentrum”

1. Der Begriff “Zentrum” ist im Zusammenhang mit der St?tte ?rztlicher Berufsausübung einem Bedeutungswandel unterlegen. 2. Im Bereich der ambulanten ?rztlichen Berufsausübung gilt der überkommene Zentrumsbegriff zumindest nicht mehr, wenn die ?rztliche Berufsausübung im Rahmen eines Medizinischen Versorgungszentrums erfolgt. (Leits?tze der Bearbeiterin)     

Autoantibodies against bactericidal/permeability-increasing protein in patients with cystic fibrosis

Cystic fibrosis (CF), a genetic disorder, is characterized by chronic pulmonary infection/inflammation which leads to respiratory failure. The presence of anti-neutrophil cytoplasmic autoantibodies (ANCA) has previously been observed in the sera of patients with CF. In view of the known relationship of ANCA with primary vasculitis and of their putative pathogenetic role in these disorders, we studied the presence, specificity and isotype of ANCA and their clinical associations in 66 adult CF patients. None of the 66 CF samples had autoantibodies to the major ANCA antigens, proteinase 3 or myeloperoxidase. However, 60/66 (91%) CF samples contained IgG and 55/66 (83%) IgA, autoantibodies to bactericidal/permeability increasing protein (BPI), a recently characterized ANCA specificity. All the IgA anti-BPI-positive samples were also IgG anti-BPI-positive. The autoantibody specificity was confirmed by inhibition assay and immunoblotting of CF sera against a neutrophil granule preparation. Furthermore, in this cross-sectional study, anti-BPI levels were inversely correlated with the observed reductions in FEV1 and FVC (IgA anti-BPI and FEV1: r = 0.508, <it>p</it> &lt; 0.0001), and both IgG and IgA anti-BPI levels were higher in CF patients with secondary vasculitis (<it>n</it> = 6) than in those without (<it>p</it> &lt; 0.05). ANCA with specificity for BPI were present in the majority of CF sera in this study and autoimmune processes may be associated with the development of pulmonary injury in CF.      

大鼠眼外肌成肌细胞的增殖及分化特征

目的:完善眼外肌成肌细胞体外培养、鉴定的方法及观察其生物学特性。方法:实验于2005-02/08在青岛大学医学院附院中心实验室(省级实验室)完成。取出生后3～7d的大鼠,通过大鼠眼外肌细胞的取材、分离、消化、培养等技术,观察细胞的形态、生长曲线、细胞融合率,观察大鼠眼外肌卫星细胞的增殖与分化能力,利用成肌细胞标记物α-横纹肌肌动蛋白、中间丝结蛋白免疫细胞化学染色对所获得的细胞进行鉴定。结果:①成肌细胞的生长情况:在生长培养基作用下,细胞增殖旺盛;在分化培养基条件下,细胞分化良好,可融合成肌管。②成肌细胞融合率:在24h和48h融合率提高明显,72h达高峰,之后不再变化。③细胞免疫化学检测结果:α-横纹肌肌动蛋白和中间丝结蛋白免疫细胞化学染色阳性。结论:体外培养的大鼠眼外肌卫星细胞具有良好的增殖与分化能力,其生物学特征同骨骼肌卫星细胞。     

Ovarian structure and hormonal status of the UChA and UChB adult rats in response to ethanol

Objectives

In females, chronic alcoholism has a current and dangerous incidence to fertility. This work had the goal of elucidating the alterations on the ovary of UChA and UChB adult rats (ethanol 10% (v/v) voluntary drinkers).

Study design

After the treatment period, 42 female rats divided into three experimental groups (UChA, UChB and Wistar) suffered decapitation and their ovaries were removed and processed to further analysis on light and electron microscopy. The ovary was entirely sliced and stained by hematoxylin–eosin, toluidine blue, periodic acid Schiff (PAS) and Masson's tricromic. Thereby, the enzymatic reaction to acid and alkaline phosphatase, estral cyclicity, reproductive hormonal status and frequency in oestrous-related ovarian structures were assigned.

Results

The UChB rats showed an increase in body mass gain index and the ovaries relative weight was significantly lower comparing to the other groups. UCh rats presented the longest estral cycle durations and also persistent oestrous phasis, with uninterrupted cycles. Advanced follicular atresia was common in UCh animals, and degenerating intracellular fragments could be observed through acid phosphatase and electron microscopy techniques.

Conclusions

There were some estral cyclicity irregularities caused by chronic ethanol intake in the UCh groups which were consequently reflected as morphologic injury in the ovary structure.     

Tobacco smoke affects expression of peroxisome proliferator-activated receptor-γ in monocyte/macrophages of patients with coronary heart disease

Background and purpose:

Tobacco smoke represents a relevant risk factor for coronary heart disease (CHD). Although peroxisome proliferator-activated receptor (PPAR)γ activation reduces inflammation and atherosclerosis, expression of PPARγ in cells and its modulation by smoking are poorly investigated. We previously reported that monocyte/macrophages from healthy smokers exhibited an enhanced constitutive expression of PPARγ. Here, we evaluated PPARγ expression and basal cytokine release in monocytes and monocyte-derived macrophages (MDMs) from 85 CHD patients, classified by their smoking habit (smokers, non-smokers and ex-smokers), and assessed the role of PPARγ ligands in this context.

Experimental approach:

PPARγ protein was detected by Western blot and semi-quantified by PPARγ/β-actin ratio; cytokine release was measured by elisa and nuclear factor-kappaB (NF-κB) translocation by electrophoretic mobility shift assays.

Key results:

As compared to the other groups, MDMs from smoker CHD patients exhibited a reduced PPARγ/β-actin ratio and an increased spontaneous release of tumour necrosis factor-α (TNF-α) and interleukin-6, but with no major variations in monocytes. In cells from selected CHD patients, rosiglitazone inhibited TNF-α release and NF-κB translocation induced by phorbol-12-myristate 13-acetate. The selective PPARγ antagonist GW9662 reversed these effects, with some variations related to smoking habit.

Conclusions and implications:

In CHD patients, exposure to tobacco smoke profoundly affected PPARγ expression, and this was related to levels of secretion of pro-inflammatory cytokines. MDMs from CHD smokers showed the lowest PPARγ expression and released more inflammatory cytokines. Moreover, rosiglitazone''s ability to inhibit cytokine release and its reversal by GW9662 clearly indicated PPARγ involvement in these changes in CHD patients.     

Mobilization of early hematopoietic progenitor cells with BB-10010: a genetically engineered variant of human macrophage inflammatory protein- 1 alpha

BB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha with improved solution properties. We show here that it mobilizes stem cells into the peripheral blood. We investigated the mobilizing effects of BB-10010 on the numbers of circulating 8-day spleen colony-forming units (CFU-S8), CFU-S12, and progenitors with marrow repopulating ability (MRA). A single subcutaneous dose of BB-10010 caused a twofold increase in circulating numbers of CFU-S8, CFU-S12, and MRA 30 minutes after dosing. We also investigated the effects of granulocyte colony-stimulating factor (G- CSF) and the combination of G-CSF with BB-10010 on progenitor mobilization. Two days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA progenitors by 25.7-, 19.8-, and 27.7-fold. A single administration of BB-10010 after 2 days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA even further to 38-, 33-, and 100- fold. Splenectomy resulted in increased circulating progenitor numbers but did not change the pattern of mobilization. Two days of treatment with G-CSF then increased circulating CFU-S8, CFU-S12, and MRA by 64-, 69-, and 32-fold. A single BB-10010 administration after G-CSF treatment further increased them to 85-, 117-, and 140-fold, respectively, compared with control. We conclude that BB-10010 causes a rapid increase in the number of circulating hematopoietic progenitors and further enhances the numbers induced by pretreatment with G-CSF. BB- 10010 preferentially mobilized the more primitive progenitors with marrow repopulating activity, releasing four times the number achieved with G-CSF alone. Translated into a clinical setting, this improvement in progenitor cell mobilization may enhance the efficiency of harvest and the quality of grafts for peripheral blood stem cell transplantation.