Search

The aim of this study was to determine if micro-(mi-)RNAs are involved in the previously reported inverse correlation between the antileukoproteinase SLPI, HPV, and smoking habit of head and neck squamous cells carcinoma (HNSCC) patients.

Hintergrund: Für Deutschland liegen keine aktuellen Daten über Antibiotikaverordnungsraten bei Halsschmerzpatienten in Hausarztpraxen vor. Bei zunehmenden Antibiotikaresistenzen auch im ambulanten Bereich sind Kenntnisse über das Vorgehen von Hausärzten bei Halsschmerzpatienten Voraussetzung für Interventionen mit dem Ziel eines möglichst restriktiven Einsatzes von Antibiotika. Hauptindikation für eine Antibiotikagabe bei Halsschmerzen ist die Streptokokken-A-Pharyngitis. Methoden: In einer Querschnittstudie wurde die Behandlung von 475 Halsschmerzpatienten in 58 Praxen in Schleswig-Holstein von Juni bis Oktober 2010 erfasst. Primäre Zielgröße war die Antibiotikaverordnungsrate, sekundär wurden die Häufigkeiten von Labortests, Verdachtsdiagnosen und Art der Antibiotikagabe sowie Empfehlungen anderer Maßnahmen untersucht. Der Einfluss patienten-, praxis- oder arztspezifischer Faktoren und der Diagnosen auf die Rate von Antibiotikaverordnungen wurde in uni- und multivariaten statistischen Verfahren bewertet. Ergebnisse: 41% der Patienten erhielten bei der Erstvorstellung ein Antibiotikum (95%-KI: 37–46%). Die Antibiotikagaben waren signifikant abhängig von den Beschwerden der Patienten und den meist unspezifischen Verdachtsdiagnosen. Rachenabstriche wurden selten durchgeführt. Nur 40% der Verordnungen fielen auf Penicillin. Eine Empfehlung zu sonstigen Maßnahmen wurde bei 66% der Konsultationen dokumentiert, darunter Ibuprofen oder Paracetamol bei 17% aller Konsultationen. Schlussfolgerungen: Die Antibiotikaverordnungsrate ist mindestens doppelt so hoch wie die anzunehmende Zahl an Streptokokken-A-Pharyngitiden. Die Verdachtsdiagnosen deuten auf große diagnostische Unsicherheit hin.

In melanoma, the mitogen-activated protein (MAP) kinase pathway plays a crucial oncogenic role. Recent studies identified additional genetic alterations, eg, TERT-promoter mutations. Up to 8% of melanoma patients present with multiple primary melanomas (MPMs). The pathogenesis is not fully understood, and data on the genetic diversity of MPMs are limited. To identify putative diagnostic and therapeutic consequences, we assessed the mutational status of the BRAFand NRASgenes and TERTpromoter in patients with MPMs. The study cohort consisted of 96 patients with 237 malignant melanomas. The BRAF, NRAS, and TERT-promoter genotypes were assessed in all MPMs and were correlated with patients' clinicopathological characteristics. BRAFmutations were found in 84 melanomas (35.4%), NRASmutations, in 33 (14.0%); and TERT-promoter mutations, in 112 (47.3%). Mutation patterns were concordant between first and subsequent primary tumors in 23.9% of patients and were discordant in 61.4% of patients. The genetic alterations were partially different in 14.7% of patients. By Cox regression analysis, only the NRASmutation had a significant negative prognostic impact on time to progression to stage III (P = 0.016) and on distant metastasis–free survival (P = 0.032). In the majority of primary melanomas in patients with MPMs, BRAF, NRAS,and TERT-promoter genotypes were discordant. Thus, molecular testing for targeted therapy should be performed on metastatic tissue and not on primary tumors.

The elastic function of the aorta in patients with transposition of the great arteries after arterial switch operation (ASO) is suspected to be important for long-term prognosis.

This study was designed to trace bone marrow-derived stromal cells (MSC) after implantation in an ectopic rat model of bone tissue engineering. MSC were isolated from adult donor rats, expanded, seeded on a hydroxyapatite/β-tricalcium phosphate bone graft substitute (Straumann®BoneCeramic), and cultivated until confluent. Before subcutaneous implantation of seeded constructs and controls (unseeded bone graft substitute) in isogenic rats (n= 32), cells were labeled with the fluorescent dye carboxyfluoresceine-diacetate-succinimidyl-ester. Specimens were harvested at sacrifice on day 1, 3, 7, or 14 after implantation (n= 8 per group) and processed for histology (hematoxylin and eosin, CD68, 4′,6-diamidino-2-phenylindol). Carboxyfluoresceine-diacetate-succinimidyl-ester-labeled transplanted cells were quantified in decalcified sections (50 fields of view per specimen) at 488 nm. Over time, transplanted cells decreased in number from 31.3 ± 2.3 (day 1) to 9.2 ± 1.1 (day 3) and 0.3 ± 0.1 (day 7) (p< 0.001). Fourteen days postimplantation MSC could no longer be identified. Additionally, starting on day 3 postimplantation, cellular disintegration was noted. Multinucleated giant cells were present in constructs and controls on day 7 and increased to day 14 postimplantation. These results indicate that ectopically transplanted MSC survive for a rather short time after implantation. Possible reasons for early cell death are discussed.

In the current study the authors attempted to evaluate genetic alterations in a large set of primary ovarian carcinomas and to compare the genetic findings with clinical parameters such as grade of tumor differentiation. This strategy was applied to identify chromosomal regions containing genes associated with tumor progression. Genetic imbalances were assessed in 106 primary ovarian carcinomas using comparative genomic hybridization (CGH). CGH was applied because it is a powerful tool with which to screen the entire genome of a tumor for genetic changes by highlighting regions of altered DNA sequence copy numbers (deletions and amplifications). Multivariate statistical standard procedures were used to determine an association between tumor grading and genetic alterations. One hundred three carcinomas showed aberrant CGH profiles. The most frequent alterations were amplifications of 8q, 1q, 20q, 3q, and 19p, which occurred in 69–53% of tumors, and underrepresentations of 13q, 4q, and 18q, which occurred in 54–50% of tumors. Undifferentiated ovarian carcinomas (World Health Organization Grade 3) were found to be correlated significantly with underrepresentation of 11p and 13q as well as with overrepresentation of 8q and 7p (P = 0.001, 0.001, 0.01, and 0.027, respectively). However, 12p underrepresentation and 18p overrepresentation were significantly more frequent in well and moderately differentiated tumors (P = 0.01 and 0.004, respectively). To facilitate the interpretation and clinical application of the results of the current study, the significant aberrations were translated into a score system. This score system can be used easily for the prediction of an undifferentiated phenotype with a specificity and sensitivity of 79% and 86%, respectively. The current study data show that primary ovarian carcinomas are based on consistent genetic alterations that most likely are important for the development of this tumor entity. The correlation between certain aberrations and undifferentiated carcinomas may help to discriminate between primary and secondary genetic events and may indicate the location of those genes involved in cellular functions associated with tumor progression and the development of anaplastic and aggressive phenotypes. Cancer 2001;91:534–40. © 2001 American Cancer Society.

Tumour grade is one of the prognostic factors in pancreatic ductal adenocarcinoma, but its value is controversial. In this study, the predictive value and the reproducibility of the WHO grading system were reconsidered and the possibility of supplementing it with the immunohistochemically assessed proliferative activity was investigated. Seventy resected ductal adenocarcinomas of the head of the pancreas were evaluated. A total of 60 HPF fields on two to four sections per tumour were screened for glandular differentiation, mucin production, mitosis, and nuclear atypia by two observers with different degrees of experience. Each criterion was scored and the grade was calculated from the mean value of all single scores. Corresponding slides were immunohistochemically stained with the proliferation marker Ki-S5. The percentage of positive nuclei was assessed and a proliferation index (PI) assigned (&lt;10%=1; 10–50%=2; >50%=3). Multivariate analysis (Cox regression) identified grade and R stage as the most significant factors for predicting survival. The PI determined on the basis of Ki-S5 staining did not prove to be an independent prognostic factor. In 30 of 70 carcinomas, it correlated with the tumour grade. Within a given tumour grade, the cases with the least favourable prognosis could be distinguished on the basis of their PI. The inter-observer variability was considerable, with the main differences occurring in the group of G1 tumours. According to the refined WHO criteria, the histopathological grade of pancreatic ductal carcinoma is an important independent prognostic factor, but reproducibility depends on the expertise of the observer. Criteria that relate to cellular and structural differentiation seem to be more predictive than those related to proliferation. Copyright © 2000 John Wiley & Sons, Ltd.

Tumour grade is one of the prognostic factors in pancreatic ductal adenocarcinoma, but its value is controversial. In this study, the predictive value and the reproducibility of the WHO grading system were reconsidered and the possibility of supplementing it with the immunohistochemically assessed proliferative activity was investigated. Seventy resected ductal adenocarcinomas of the head of the pancreas were evaluated. A total of 60 HPF fields on two to four sections per tumour were screened for glandular differentiation, mucin production, mitosis, and nuclear atypia by two observers with different degrees of experience. Each criterion was scored and the grade was calculated from the mean value of all single scores. Corresponding slides were immunohistochemically stained with the proliferation marker Ki‐S5. The percentage of positive nuclei was assessed and a proliferation index (PI) assigned (<10%=1; 10–50%=2; >50%=3). Multivariate analysis (Cox regression) identified grade and R stage as the most significant factors for predicting survival. The PI determined on the basis of Ki‐S5 staining did not prove to be an independent prognostic factor. In 30 of 70 carcinomas, it correlated with the tumour grade. Within a given tumour grade, the cases with the least favourable prognosis could be distinguished on the basis of their PI. The inter‐observer variability was considerable, with the main differences occurring in the group of G1 tumours. According to the refined WHO criteria, the histopathological grade of pancreatic ductal carcinoma is an important independent prognostic factor, but reproducibility depends on the expertise of the observer. Criteria that relate to cellular and structural differentiation seem to be more predictive than those related to proliferation. Copyright © 2000 John Wiley & Sons, Ltd.

AbstractBackground:Ciprofloxacin (CFLX) is a fluoroquinolone antibiotic with a broad antimicrobial spectrum. This study was performed to examine the retinal toxicity of free and liposome-incorporated CFLX in rabbit eyes after intravitreal injection. Materials and Methods:Free CFLX in doses of 100, 250, 500, 1,000 and 2,000 µg was injected into the midvitreous of rabbit eyes (n = 28). To prolong the intravitreal antibacterial level, CFLX was incorporated into multilamellar liposomes: 0.1 ml of this suspension (≙ 273.6 µg CFLX) was injected into the midvitreous of a second group of rabbit eyes (n = 6). The other eye served as a control and received normal saline solution or empty liposomes, respectively. Before injection and at the end of follow-up an electroretinogram (ERG) was obtained. After a follow-up of 1, 14 and 28 days the animals were perfused with glutaraldehyde and the eyes were examined by light and transmission electron microscopy. Results:Significant reduction of the ERG was observed after 2,000 µg free CFLX in 4 out of 6 eyes after 14 days. Fourteen days after injection of 2,000 µg CFLX the central retina showed pigmentary changes in 4 out of 6 eyes. In the second group the ERG as well as the histologic studies did not reveal any pathologic changes after injection of liposome-incorporated CFLX compared to the control eyes. Conclusion:In therapeutic doses of 100–500 µg, free CFLX does not have retinal toxicity in rabbit eyes. No retinal toxicity was observed after intravitreal injection of liposome-incorporated CFLX.

Resection specimens from 145 patients with primary B-cell gastric lymphoma at stage IE(n = 88) and at stage IIE(n = 57) were investigated. Histologically, low-grade malignant B-cell lymphomas arising from the mucosa-associated lymphoid tissue, including immunocytoma (n = 71), could be distinguished from high-grade malignant B-cell lymphomas with (n = 25) and without (n = 49) evidence of a lowgrade component. The very rare low-grade B-cell lymphomas of centroblastic-centrocytic, centrocytic, and plasmacytic type were not considered. All patients had undergone primary gastric resection, and 65 received additional chemotherapy (n = 33), radiotherapy (n = 22), or both (n = 10). Actuarial overall survival rates calculated by the Kaplan-Meier life-table method were 76% after 5 years and 58% after 10 years. According to the Mantel test and a multivariate analysis using the Cox regression method, patients at stage IEhad a significantly better survival probability than those at stage IIE(P< 0.0001); 5-year survival rates were 87% and 61%, respectively. The survival probability for low-grade malignant lymphomas was significantly better than for tumors with secondary high-grade transformation (P< 0.05) or for primary high-grade lymphomas (P< 0.0001), whereas the two high-grade groups were not significantly different. Five-year survival rates were 91% for low-grade, 73% for secondary high-grade, and 56% for primary high-grade malignant lymphomas. Retrospectively, no significantly different survival rates were found between patients who had undergone gastric resection alone and patients who had received additional treatment. However, survival analyses showed that classification and grading according to the histopathological concept of mucasa-associated lymphoid tissuederived gastric lymphomas into low-grade B-cell lymphomas of mucosa-associated lymphoid tissue type and high-grade B-cell lymphomas with or without evidence of a low-grade component has great prognostic relevance.

At the University Hospital in Kiel data on the medical care and administration of individual patients is collected in a hospital information system. The description leads to lists of all cases treated, arranged according to basic data descriptions, and to tabulations of aggregated data. The aim of these statistics is to provide an overview of the collected data. At present the statistics can do little more than offer some general impressions about the frequency of serious diseases requiring hospitalization and health-care needs of a particular region; this is because they are selected and therefore biased and misleading.An accurate epidemiological view of a region to evaluate the quality, efficiency and cost of its health-care system can only be obtained if all the hospitals in that area are producing summarized information. So correlation of population statistics, broken down by patients' residential area and the hospital means for evaluating the health-care demands and consumption of a particular population, and for regional planning when figures for catchment area and attraction rate are produced.Au Centre Hospitalier Universitaire de Kiel, les informations médicales et administratives sont enregistrées sur un système de gestion hospitalier. Ceci permet d'editer des listes de touslescas traités, suivant descriteres definis à l'avance. Ces statistiques permettent d'avoir une vue d'ensemble des informations collectées. Le système actuel fait mieux que de donner la fréquence des maladies graves ou que d'indiquer les besoins de santě d'une région. En effet, jusqu' à présent, les données étaient selectionées de façon biaisée.Au niveau d'une région, une étude épidémiologique ne peut ětre menée à bien que si tous les hôpitaux y participent. De cette façon peuvent ětre définies des statistiques de population, les demandes de soins, la consommation médicale, les planifications régionales, les zones d'attractions hospitaliercs et les moyens necessaires pour obtenir ces indications.

In granulomatosis with polyangiitis (GPA), a complex autoimmune small-vessel vasculitis frequently associated with chronic necrotizing inflammation of the nasal mucosa, elevated nasal Staphylococcus (S.) aureus carrier rates are a risk factor for relapse. As cytokines are primarily involved in the regulation of defense against potentially pathogenic microorganisms, the aim of this study was to compare healthy individuals and GPA patients with respect to their baseline cytokine expression of nasal epithelial cells (NEC), which form the first barrier against such triggers. The ability of S. aureus to influence the nasal microenvironment's cytokine secretion was assessed by exemplary stimulation experiments.