A change in inflammatory footprint precedes plaque instability: a systematic evaluation of cellular aspects of the adaptive immune response in human atherosclerosis.

BACKGROUND: Experimental studies characterize adaptive immune response as a critical factor in the progression and complications of atherosclerosis. Yet, it is unclear whether these observations translate to the human situation. This study systematically evaluates cellular components of the adaptive immune response in a biobank of human aortas covering the full spectrum of atherosclerotic disease. METHODS AND RESULTS: A systematic analysis was performed on 114 well-characterized perirenal aortic specimens with immunostaining for T-cell subsets (CD3/4/8/45RA/45RO/FoxP3) and the Th1/non-Th1/Th17 ratio (CD4(+)T-bet(+)/CD4(+)T-bet(-)/CD4(+)/interleukin-17(+) double staining). CD20 and CD138 were used to identify B cells and plasma cells, while B-cell maturation was evaluated by AID/CD21 staining and expression of lymphoid homeostatic CXCL13. Scattered CD4 and CD8 cells with a T memory subtype were found in normal aorta and early, nonprogressive lesions. The total number of T cells increases in progressive atherosclerotic lesions (≈1:5 CD4/CD8 T-cell ratio). A further increase in medial and adventitial T cells is found upon progression to vulnerable lesions.This critical stage is further hallmarked by de novo formation of adventitial lymphoidlike structures containing B cells and plasma cells, a process accompanied by transient expression of CXCL13. A dramatic reduction of T-cell subsets, disappearance of lymphoid structures, and loss of CXCL13 expression characterize postruptured lesions. FoxP3 and Th17 T cells were minimally present throughout the atherosclerotic process. CONCLUSIONS: Transient CXCL13 expression, restricted presence of B cells in human atherosclerosis, along with formation of nonfunctional extranodal lymphoid structures in the phase preceding plaque rupture, indicates a "critical" change in the inflammatory footprint before and during plaque destabilization.

[Acute appendicitis mimicking cholecystitis. Case reports and review with focus on medicolegal aspects]. / Akute Appendizitis unter dem klinischen Bild einer Cholezystitis. Falldarstellungen und Review aus Sicht der MDK-Behandlungsfehlerbegutachtung.

Since 1955 simultaneous presentation of acute appendicitis und acute cholecystitis have been described. These cases are understood as concomitance on the one hand and as imitation or induction of acute cholecystitis due to acute appendicitis. In laparoscopic surgery for inflammatory diseases, in particular acute cholecystitis, exploration of the entire abdomen should be more than cursory. In remarkable postoperative courses after cholecystectomy in acute cholecystitis, acute appendicitis should be taken into account if it could not be excluded intraoperatively.

Visualizing TGF-ß and BMP signaling in human atherosclerosis: a histological evaluation based on Smad activation.

BACKGROUND: The TGF-ß superfamily members transforming growth factor-ß (TGF-ß/Activin) and bone morphogenetic proteins (BMP) have been implicated in the pathogenesis of atherosclerosis. However, their role in human disease remains controversial. In this study we used Smad phosphorylation as a read out for TGF-ß and BMP signaling during the initiation, progression and (de)stabilization of human atherosclerotic disease. MATERIAL AND METHODS: A systematic analysis was performed in 114 peri-renal aortic patches (stained with Movat Pentachrome, H&E, pSmad2, pSmad1,5,8 and PAI-1) covering the entire atherosclerotic spectrum (van Dijk, 2010). Immunostaining against T-cells (CD3) and monocytes and macrophages (CD68) was used to explore a putative association between TGF-ß and BMP signaling and vascular inflammation. RESULTS: Smad phosphorylation was present within the normal arterial wall in approximately 10% of the endothelial cells and intimal smooth muscle cells. A significant increase in pSmad2 and pSmad1,5,8 positivity was found in non-progressive lesions (>50% positivity). No further increase or decrease was found in the progressive atherosclerotic lesions, vulnerable and stabilized lesions. No association was found between TGF-ß and BMP signaling and CD3 and CD68 expression, nor cap thickness. CONCLUSION: Activation of the TGF-ß and BMP pathways is an early event in atherosclerotic lesion formation. No significant relationships were found between Smad phosphorylation and vessel wall inflammation or plaque vulnerability.

The effects of a custom-made lead collar on dose rates of patients treated with 131I.

We studied the effects of a custom-made lead collar on dose rates and hospitalization days of patients treated with high doses (>400 MBq) of radioiodine (131I). Between October 2005 and March 2006, the dose rates of 28 consecutive patients were studied. Dose rates of patients with and without the collar (5.5 mm lead) were measured daily until the rate dropped below the discharge dose rate of 20 microSv-1 h at 1 m. Age, sex, 131I dose, uptake, thyroid disorder, and days of isolated hospitalization were recorded. The difference in mean dose rate with or without the collar was analyzed by t test or Mann-Whitney test, as appropriate. Twenty-eight patients (7 male, 21 female; mean age, 57 y; range, 29-82 y) were analyzed. Nine patients suffered from Graves' disease, 9 from toxic nodular goiter, and 10 from non-toxic nodular goiter. Patients were treated with a mean dose of 1,647 MBq 131I (range, 511-3,276 MBq). The mean anterior dose rates were 28 +/- 12 microSv-1 h at 1 m and 11 +/- 6 microSv-1 h at 1 m without and with the lead collar, respectively (p < 0.001). The mean reduction in dose rate for patients wearing the collar was 61 +/- 13%. The mean hospital stay was 2.6 +/- 1.3 days without the collar vs. 1.2 +/- 0.6 days with the collar (p < 0.001). A custom-made lead collar significantly reduced dose rates and could reduce compulsory hospitalization, especially in toxic- and non-toxic nodular goiter.

Local and distant recurrences in rectal cancer patients are predicted by the nonspecific immune response; specific immune response has only a systemic effect--a histopathological and immunohistochemical study.

BACKGROUND: Invasion and metastasis is a complex process governed by the interaction of genetically altered tumor cells and the immunological and inflammatory host response. Specific T-cells directed against tumor cells and the nonspecific inflammatory reaction due to tissue damage, cooperate against invasive tumor cells in order to prevent recurrences. Data concerning involvement of individual cell types are readily available but little is known about the coordinate interactions between both forms of immune response. PATIENTS AND METHODS: The presence of inflammatory infiltrate and eosinophils was determined in 1530 patients with rectal adenocarcinoma from a multicenter trial. We selected 160 patients to analyze this inflammatory infiltrate in more detail using immunohistochemistry. The association with the development of local and distant relapses was determined using univariate and multivariate log rank testing. RESULTS: Patients with an extensive inflammatory infiltrate around the tumor had lower recurrence rates (3.4% versus 6.9%, p = 0.03), showing the importance of host response against tumor cells. In particular, peritumoral mast cells prevent local and distant recurrence (44% versus 15%, p = 0.007 and 86% versus 21%, p < 0.0001, respectively), with improved survival as a consequence. The presence of intratumoral T-cells had independent prognostic value for the occurrence of distant metastases (32% versus 76%, p < 0.0001). CONCLUSIONS: We showed that next to properties of tumor cells, the amount and type of inflammation is also relevant in the control of rectal cancer. Knowledge of the factors involved may lead to new approaches in the management of rectal cancer.

Detection of parvovirus B19 infection in first and second trimester fetal loss.

Fetal and placental tissues and maternal sera from a series of 273 cases of first and second trimester fetal loss were collected to detect the frequency of parvovirus B19 infection. In addition, fetal tissues were studied for the presence of congenital anomalies. Serology of maternal sera, histology of fetal tissues and placenta, polymerase chain reaction (PCR), in situ hybridization (ISH), and immunohistochemistry (IHC) were used for the detection of parvovirus B19 infection. Sera were tested for B19-specific immunoglobulin M (IgM) and/or IgG using an enzyme-linked immunosorbent assay technique. Based on serology, 149 cases not related to B19 infection were excluded from further analysis. Two of the remaining 124 cases (0.7% of all 273 cases) had parvovirus B19-specific IgM and IgG at the time of abortion, indicating a recent maternal parvovirus B19 infection. In our histological examination, 10 cases contained nuclear vacuolization in fetal erythroid progenitor cells, either in fetal tissues (n = 2) or in placental tissue (n = 8). However, this vacuolization was considered a fixation artifact and not identical to parvovirus B19-specific nuclear inclusions described in previous reports. Only 1 of these 10 cases had parvovirus B19 DNA detectable in placental tissue by PCR analysis. Neither in this case nor in any of the other cases tested was parvovirus B19 DNA or protein detectable by ISH or IHC, respectively. In none of 41 cases in which fetal tissues were available were congenital anomalies found. In conclusion, the frequency of maternal parvovirus B19 infection in this series of fetal losses is low (0.8%). This low frequency does not allow any conclusions with regard to the occurrence of congenital anomalies resulting from parvovirus B19 infection and the usage of nuclear histology for the detection of fetal parvovirus B19 infection is considered a nonspecific parameter that requires confirmation by PCR.

[Behavior of postoperative adhesions after intraperitoneal administration of fibrinolytic drugs in a rat model]. / Verhalten postoperativer Adhäsionen nach intraperitonealer Applikation von Fibrinolytika in einem Rattenmodell.

In a rat model, the effect of the intraperitoneal application of fibrinolytic agents on the development of adhesions was examined. Streptokinase and TPA reduced sero-serosal adhesions significantly, whereas urokinase did not reduce them. Intravascular coagulation was not affected.

[Results of surgical management of unstable pertrochanteric femoral fractures with the dynamic hip screw and T-plate]. / Ergebnisse der operativen Versorgung instabiler pertrochantärer Femurfrakturen mittels DHS und T-Platte.

The dynamic hip screw (DHS) is a widely used method of osteosynthesis. Nevertheless, supplying instable pertrochanteric fractures is problematic because the gliding screw may cause a considerable dislocation of fragments in lateral direction. Is there any alternative method disposable, bearing stability of DHS- osteosynthesis can be improved by adding a lateral T-plate. We reached full bearing stability in four cases.

[Cemented bipolar prosthesis in multimorbidity patients with coxarthrosis. Short- and intermediate-term results]. / Zementierte bipolare Prothesen bei multimorbiden Koxarthrose-Patienten. Kurz- und mittelfristige Ergebnisse.

The treatment of coxarthrosis with the cemented Duopleet prosthesis represents an efficient alternative to total hip prosthesis in elderly and polymorbid patients. The early results show a tolerable rate of complications. The patients can be mobilized early. The mortality seems to be low. Medium-term results are satisfactory. The rate of protrusions is lower than in patients with common femoral head prosthesis. Paraarticular ossifications are seen frequently. In numerous patients we found pain with projection to the operated hip.

[Significance of CEA and CA 19-9 for after care of curatively resected colorectal cancers]. / Die Bedeutung von CEA und CA 19-9 für die Nachsorge kurativ resezierter kolorektaler Karzinome.

The monitoring of CEA is valuable in the follow-up after curative resection of colorectal cancer and contributes to the early detection of local recurrence and distant metastases. The simultaneous detection of the CA 19-9 does not lead to a substantial advantage. The recurrences and especially the metastases detected by the monitoring of the tumour markers frequently are unresectable. In patients with elevated tumour markers without other evidences of recurrence or metastases the indication for a second-look operation should be considered cautious because elevated tumour markers are found in patients with benign diseases also.

[Obstructive jaundice in proximal pancreatitis after sclerosing of a bleeding duodenal ulcer]. / Verschlussikterus bei Kopfpankreatitis nach Sklerosierung eines blutenden Duodenalulkus.

Two weeks after successful endoscopic sclerotherapy of a bleeding duodenal ulcer a fifty-year old male patient developed a benign enlargement of the head of the pancreas and obstructive jaundice. He underwent exploratory laparotomy with choledocho-jejunostomy because there was no evidence of malignant disease. The enlargement of the head of the pancreas and obstructive jaundice are considered to be symptoms of a pancreatitis as a complication of the endoscopic sclerotherapy.

[Significance of ofloxacin for the treatment of infection-exacerbated chronic obstructive lung disease]. / Die Bedeutung von Ofloxacin für die Behandlung der infektexacerbierten COLD.

The success achieved with treatment employing 2 X 200 mg oral ofloxacin administered over a period of 10 in 28 patients with COLD exacerbated by infection and requiring inpatient treatment, was comparable with that observed in 29 patients receiving treatment with established antibiotics. In elderly patients, high plasma levels of ofloxacin and frequent states of confusion were observed.

Polysaccharide localization, coccolith formation, and Golgi dynamics in the coccolithophorid Hymenomonas carterae.

The periodic acid-thiocarbohydrazide-silver proteinate staining technique according to Thiéry (1967) was employed for visualization of the ultrastructural localization of polysaccharides in the coccolithophorid alga Hymenomonas carterae . Preferential staining was observed in the Golgi apparatus, including constituents and precursors of "scales" and " coccoliths " (scales with a rim of elaborate CaCO3 crystals), which are extruded and become part of the cell wall. Cells fixed in the presence of the polyanion-precipitating agent cetylpyridiniumchloride showed a voluminous coat over the crystalline matter of the coccolith giving the extracellular coccoliths the appearance of being glued together. Soluble acid polysaccharides are thought to occur in the coat. Evidence is presented that the coat and the crystalline matter are produced simultaneously. The excellent stainability of the Golgi apparatus allowed study of its morphology in considerable detail, and permitted a tentative reconstruction of the formation of coccoliths and scales and of the Golgi dynamics in general. The question of whether Golgi cisternae are mobile or static entities is dealt with.

Endocytosis in absorptive cells of cultured human small-intestinal tissue: effect of cytochalasin B and D.

The effect of cytochalasin B (CB) and cytochalasin D (CD) on the endocytotic uptake of horseradish peroxidase (HRP) by intestinal absorptive cells was investigated by morphometric methods. The results showed that CD inhibited endocytosis considerably, and without any detrimental side-effects. CB had hardly any effect on the endocytosis of HRP, but caused a significant decrease in the number of apical vesicles and tubules involved in the transport of cell-coat glycoproteins from the Golgi apparatus to the brush border. Electron-microscopic autoradiographic analysis of the effect of CD showed that although endocytosis is inhibited significantly by the drug, the amount of radiolabelled cell-coat material entering the lysosome-like bodies was unaltered compared with control cultures. These observations support our hypothesis that the cell-coat glycoproteins of the absorptive cells enter the lysosome-like bodies by a crinophagic rather than by an exocytotic-endocytotic mechanism.

The effect of chloroquine on the intralysosomal degradation of cell-coat glycoproteins in the absorptive cells of cultured human small-intestinal tissue as shown by silver proteinate staining.

The effect of chloroquine on the intralysosomal degradation of cell-coat glycoproteins in cultured intestinal absorptive cell was investigated by silver proteinate staining. The results of this staining method, which is specific for carbohydrate containing macromolecules such as glycoproteins and mucopolysaccharides, showed that in the presence of the drug considerable amounts of silver proteinate-positive material accumulated in one type of lysosome-like body: the dense bodies. The staining pattern of other cell organelles was not affected by chloroquine. The presence of the drug in the culture medium also resulted in the occurrence of numerous small vesicular structures in the matrix of the dense bodies. These showed a similar size and structure to those present in the other type of lysosome-like body: the multivesicular bodies. This observation, together with earlier autoradiographical data, suggests that cell-coat material is transferred from multivesicular to dense bodies by fusion between these organelles. This study thus provides further evidence for a regulatory mechanism of cell-coat glycoprotein transport by the lysosome-like bodies in human intestinal absorptive cells.

The effect of colchicine on the intracellular transport of 3H-fucose-labelled glycoproteins in the absorptive cells of cultured human small-intestinal tissue. An autoradiographical and biochemical study.

The effect of colchicine on the intracellular transport of 3H-fucose-labelled glycoproteins in the absorptive cells of cultured biopsy specimens of the human intestine was investigated by light- and electron-microscopical autoradiography and by biochemical methods. The results showed a decrease in the radioactivity of the cell coat on the microvilli and an increase in the Golgi apparatus and in the apical vesicles and tubules. This divergence is attributed to a colchicine-induced impairment of the normal transport of cell-coat glycoproteins from the Golgi apparatus, via the apical vesicles and tubules, to the apex of the cell. The radioactivity of the lysosome-like bodies in the absorptive cells cultured with colchicine also increased. This finding supports a crinophagic function of these organelles in the degradation of excess cell-coat material.

Endocytosis in absorptive cells of cultured human small-intestinal tissue: horseradish peroxidase, lactoperoxidase, and ferritin as markers.

The occurrence of endocytotic mechanisms in human small-intestinal absorptive cells was investigated by culturing biopsy specimens in the presence of horseradish peroxidase (HRP), lactoperoxidase (LPO), and ferritin. The results indicate that both HRP and LPO entered the cells by apical endocytosis, after which they were transported via apical vesicles and tubules to the lysosome-like bodies. Ferritin, which showed a distinct affinity for the cell-coat glycoproteins, was not interiorized by the absorptive cells. These findings suggest that although human absorptive cells have an endocytotic mechanism, possibly fluid-phase endocytosis, cell-coat glycoproteins are not taken up by the cells, as indicated by the absence of ferritin in the apical vesicles and tubules, as well as the lysosome-like bodies. These findings provide indirect support for our hypothesis that the lysosome-like bodies have a function in the regulation of cell-coat glycoprotein transport via a crinophagic mechanism (fusion of apical vesicles and tubules with lysosome-like bodies) rather than via an exocytotic-endocytotic mechanism.

The effect of chloroquine on lysosomal function and cell-coat glycoprotein transport in the absorptive cells of cultured human small-intestinal tissue.

The effect of chloroquine, an inhibitor of intralysosomal catabolism, on the synthesis, transport, and degradation of cell-coat glycoproteins in absorptive cells of cultured human small-intestine tissue was investigated by morphometrical, autoradiographical, and biochemical methods. Neither synthesis nor transport of cell-coat material was affected by the drug, but culturing of the absorptive cells in the presence of chloroquine led to a dose- and time-dependent enlargement of the dense bodies; other cell structures showed no alterations. 3H-fucose-labelled material accumulated in the dense bodies of the absorptive cells of these cultures. Since no increase of beta-glucuronidase and acid phosphatase activity (both lysosomal enzymes of glycoprotein nature) was found, this accumulation of radiolabeled material can be explained as a chloroquine-mediated inhibition of the degradation of cell-coat glycoproteins. These macromolecules probably enter the lysosome-like bodies by a crino-phagic mechanism, i.e., fusion of these organelles with the apical vesicles and tubules involved in intracellular transport. These findings suggest that the lysosome-like bodies have a function in the regulating of cell-coat glycoprotein transport in human intestinal absorptive cell, i.e., the degradation of excess cell-coat material.