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1.
BMC Med Educ ; 24(1): 279, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38494509

ABSTRACT

BACKGROUND: The desire to die can occur in palliative care patients with a prevalence of up to 22%. Not every desire to die is accompanied by a pressure to act, but usually by a burden that can arise from various factors. To address this burden appropriately, health care workers should be trained. Based on an evaluated course on handling the desire to die, an elective course for medical students was developed and evaluated. In order to identify the impact of the elective course's content, a comparison of attitudes towards assisted dying with two other participant groups was conducted. Therefore, three questions from the evaluation of the elective course were used. METHOD: Online evaluation of the elective and questions addressing attitude were assessed using a five-point Likert scale. The specific outcome-based assessment was determined using the Comparative Self-Assessment Gain. The main participant group (group 1) were students who took the elective. The additional survey on attitudes towards assisted dying included undergraduate medical students who had taken compulsory palliative care courses (group 2) and physicians who had taken an introductory course in intensive care or emergency medicine (group 3). RESULTS: Group 1 (n = 13, response rate rr = 86.7%) was very satisfied with the blended learning format (100%) and the course itself (100%). They were able to deepen their knowledge (81.0%) and train skills (71.2%) through the course. In the additional surveys, there were 37 students in group 2 (rr = 66.1%) and 258 physicians in group 3 (rr = 73.6%). Willingness to assist with or accompany the various options for assisted dying varied according to the type of assistance. Among the participants, it can be summarised that the highest willingness was shown by the students of group 2 followed by the physicians of group 3 and the students of group 1. CONCLUSIONS: A course on handling the desire to die of palliative patients can deepen knowledge and train communication skills and thus support self-confidence. Dealing with the background of the desire to die, knowledge about assisted dying, but also one's own attitudes and responsibilities can influence the attitude towards assisted dying.


Subject(s)
Emergency Medicine , Students, Medical , Humans , Critical Care , Health Personnel , Knowledge
2.
Photoacoustics ; 31: 100513, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37275325

ABSTRACT

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide. Its severity is assessed using scores that rely on visual observation of the affected body surface area, the morphology of the lesions and subjective symptoms, like pruritus or insomnia. Ideally, such scores should be complemented by objective and accurate measurements of disease severity to standardize disease scoring in routine care and clinical trials. Recently, it was shown that raster-scanning optoacoustic mesoscopy (RSOM) can provide detailed three-dimensional images of skin inflammation processes that capture the most relevant features of their pathology. Moreover, precise RSOM biomarkers of inflammation have been identified for psoriasis. However, the objectivity and validity of such biomarkers in repeated measurements have not yet been assessed for AD. Here, we report the results of a study on the repeatability of RSOM inflammation biomarkers in AD to estimate their precision. Optoacoustic imaging analysis revealed morphological inflammation biomarkers with precision well beyond standard clinical severity metrics. Our findings suggest that optoacoustic mesoscopy may be a good choice for quantitative evaluations of AD that are inaccessible by other methods. This could potentially enable the optimization of disease scoring and drug development.

3.
J Magn Reson ; 310: 106662, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31837553

ABSTRACT

In EPR, spin relaxation is typically governed by interactions with the lattice or other spins. However, it has recently been shown that given a sufficiently strong spin-resonator coupling and high resonator quality factor, the spontaneous emission of microwave photons from the spins into the resonator can become the main relaxation mechanism, as predicted by Purcell. With increasing attention on the use of microresonators for EPR to achieve high spin-number sensitivity it is important to understand how this novel regime influences measured EPR signals, for example the amplitude and temporal shape of the spin-echo. We study this regime theoretically and experimentally, using donor spins in silicon, under different conditions of spin-linewidth and coupling homogeneity. When the spin-resonator coupling is distributed inhomogeneously, we find that the effective spin-echo relaxation time measured in a saturation recovery sequence strongly depends on the parameters for the detection echo. When the spin linewidth is larger than the resonator bandwidth, the different Fourier components of the spin echo relax with different characteristic times - due to the role of the resonator in driving relaxation - which results in the temporal shape of the echo becoming dependent on the repetition time of the experiment.

4.
Seizure ; 67: 30-37, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30870707

ABSTRACT

PURPOSE: To investigate the very long-term (i.e., ≥15 years) seizure, cognitive and psycho-social outcomes in resected patients (RP) with TLE compared to control patients not having undergone epilepsy surgery. METHODS: We applied a multiple case-study design including three non-resected patients (NRP) who were compared to a group of six RP. The latter were matched to the NRP according to clinical-demographic data. Outcome measures were various seizure, cognitive, and psycho-social variables. RESULTS: Patients were 56-72 years old. Seizure and AED outcome was more favourable among RP. RP reported better self-perceived overall health but higher subjective memory complaints. Upon formal neuropsychological testing, RP presented with lower verbal memory scores. Very long-term memory decline was evident in left-sided RP with good baseline memory scores, while RP with lower baseline performance, right-sided RP and NRP remained stable. Seizure-freedom had remarkable effects on the relationship between objective and subjective outcome: seizure-free patients, in general, subjectively reported the best psychosocial and cognitive outcome - irrespective of neuropsychological test results. CONCLUSION: Our study suggests positive effects of TLE surgery in the very long-term course of ≥15 years postoperatively. Long-term seizure-freedom appears to have the strongest impact on patients' subjectively perceived psycho-social and cognitive outcome and may even outweigh actual memory disturbances and/or decline. Overall, our data do not support the assumption of a generally accelerated cognitive decline in patients with TLE.


Subject(s)
Epilepsy, Temporal Lobe/drug therapy , Epilepsy, Temporal Lobe/surgery , Aged , Cognition , Depression , Epilepsy, Temporal Lobe/psychology , Female , Follow-Up Studies , Humans , Male , Memory , Memory Disorders/etiology , Middle Aged , Postoperative Complications , Quality of Life , Seizures/drug therapy , Seizures/psychology , Seizures/surgery , Time Factors , Treatment Outcome
5.
Oecologia ; 188(1): 263-275, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29948317

ABSTRACT

Detailed information on the nutrition of free-ranging mammals contributes to the understanding of life history requirements, yet is often quite limited temporally for most species. Reliable dietary inferences can be made by analyzing the stable carbon (C) and nitrogen (N) isotopic values (δ13C and δ15N) of some consumer tissues; exactly which tissue is utilized dictates the inferential scope. Steller sea lion (SSL) vibrissae are grown continuously without shedding and thus provide a continuous multi-year record of dietary consumption. We applied a novel kernel density approach to compare the δ13C and δ15N values along the length of SSL vibrissae with δ13C and δ15N distributions of potential prey species. This resulted in time-series of proportion estimates of dietary consumption for individual SSL. Substantial overlap in δ13C and δ15N distributions for prey species prevented a discrete species-scale assessment of SSL diets; however, a post hoc correlational analysis of diet proportion estimates revealed grouping by trophic level. Our findings suggest that adult female SSL diets in the western and central Aleutian Islands shift significantly according to season: diets contain a higher proportion of lower trophic level species (Pacific Ocean perch, northern rockfish, Atka mackerel and walleye pollock) in the summer, whereas in the winter SSL consume a much more diverse diet which includes a greater proportion of higher trophic level species (arrowtooth flounder, Kamchatka flounder, darkfin sculpin, Pacific cod, Pacific octopus, rock sole, snailfish, and yellow Irish lord).


Subject(s)
Perciformes , Sea Lions , Alaska , Animals , Diet , Female , Vibrissae
6.
Schmerz ; 30(2): 174-80, 2016 Apr.
Article in German | MEDLINE | ID: mdl-26391690

ABSTRACT

BACKGROUND: In 2009 palliative medicine was integrated into the undergraduate curriculum as cross-disciplinary subject 13 and is now part of mandatory education in German medical faculties (MF). Surveys across German MFs have shown an inhomogeneous development of this cross-disciplinary subject. The aim of this study was to assess the current state and the needs in terms of assessments in the cross-disciplinary subject 13 at German MFs. MATERIAL AND METHODS: Palliative care coordinators at German MFs were surveyed by using a standardized telephone interview. Closed-ended questions were analyzed by descriptive analysis and open-ended questions by content analysis. RESULTS: A total of 34 out of 36 MFs participated. Multiple choice tests were the major form of assessment (94.1%) and 9 MFs planned to implement another form of assessment, mainly an objective structured clinical examination (OSCE) station (55.5%). The majority of the MFs (91.2%) had no blueprint to develop assessments but conducted a review (78.8%) afterwards. A successful implementation of the assessment was mostly achieved when the concept of the assessment was felt to be suitable. The lack of human resources was found to be the most relevant obstacle for the implementation of a practical assessment format. CONCLUSION: The major form of assessment in palliative care is still a written examination, especially multiple choice tests. This format is considered to be of limited value for assessing communicative competencies and attitudes in palliative medical care. Further steps should include the development of a competence-based assessment that is also feasible for smaller MFs with limited resources.


Subject(s)
Clinical Competence/legislation & jurisprudence , Curriculum , Faculty, Medical/legislation & jurisprudence , Interdisciplinary Communication , Intersectoral Collaboration , Palliative Medicine/education , Palliative Medicine/legislation & jurisprudence , Germany , Health Plan Implementation/legislation & jurisprudence , Health Services Needs and Demand/legislation & jurisprudence , Interviews as Topic , Surveys and Questionnaires
7.
Biomed Res Int ; 2015: 762178, 2015.
Article in English | MEDLINE | ID: mdl-25649906

ABSTRACT

Nowadays prostate cancer is the most common solid tumor in men from industrialized countries and the second leading cause of death. At the ages when PCa is usually diagnosed, mortality related to cardiovascular morbidity is high; therefore, men at risk for PCa frequently receive chronic lipid-lowering and antiplatelet treatment. The aim of this study was to analyze how chronic treatment with statins, aspirin, and their combination influenced the risk of PCa detection. The tumorigenic properties of these treatments were evaluated by proliferation, colony formation, invasion, and migration assays using different PCa cell lines, in order to assess how these treatments act at molecular level. The results showed that a combination of statins and aspirin enhances the effect of individual treatments and seems to reduce the risk of PCa detection (OR: 0.616 (95% CI: 0.467-0.812), P<0.001). However, if treatments are maintained, aspirin (OR: 1.835 (95% CI: 1.068-3.155), P=0.028) or the combination of both drugs (OR: 3.059 (95% CI: 1.894-4.939), P<0.001) represents an increased risk of HGPCa. As observed at clinical level, these beneficial effects in vitro are enhanced when both treatments are administered simultaneously, suggesting that chronic, concomitant treatment with statins and aspirin has a protective effect on PCa incidence.


Subject(s)
Aspirin/pharmacology , Cell Movement/drug effects , Cell Proliferation/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Prostatic Neoplasms/epidemiology , Aged , Biopsy , Case-Control Studies , Cell Line, Tumor , Humans , Male , Prostate/pathology , Retrospective Studies
8.
Actas urol. esp ; 38(4): 232-237, mayo 2014. tab
Article in Spanish | IBECS | ID: ibc-122046

ABSTRACT

Objetivo: Analizar la influencia del sedentarismo (SE) y sobrepeso (SP) en el riesgo de detección de cáncer de próstata (CP) y su agresividad. Material y método: Se realizó biopsia prostática (BP) a 2.408 varones consecutivos, no tratados con 5 ARI, a causa de elevación sérica del PSA por encima de 4,0 ng/ml (91%) o tacto rectal sospechoso (9%). En la BP, transrectal y ecodirigida, se obtuvieron 10 cilindros, y entre 2 y 8 adicionales en función de la edad y del volumen prostático. La actividad física se evaluó mediante una encuesta (SE vs no SE) y se calculó el índice de masa corporal (normal vs SP: > 25 kg/cm2). La agresividad tumoral se evaluó según la suma de Gleason (alto grado [AG]: Gleason > 7) y el riesgo de D'Amico (alto riesgo [AR]: T > 3a o PSA > 20 o suma de Gleason > 7). Resultados: Se halló una asociación significativa entre SE (52,5%) y SP (72,9%), p > 0,001. La tasa global de detección de CP fue 35,2%. En varones con SE fue 36,7% y en no SE 33,6%, p = 0,048. La tasa global de tumores de AG fue 28,3%, 29,2% en varones con SE y 27,1% en no SE, p = 0,261. La tasa global de tumores de AR fue 35%, 39,7% en varones con SE y 29,4% en no SE, p < 0,001. Se detectó CP en un 38,1% de hombres con IMC normal y 34,3% en hombres con SP, p = 0,065. La tasa de tumores de AG fue 18,1 y 31,4% respectivamente, p < 0,001, y la tasa de tumores de AR fue 22,6 y 39,2% respectivamente, p < 0,001. La regresión logística binaria mostró que el SE fue un predictor independiente de CP, RR 0,791 (95% IC: 0,625-0,989), p = 0,030. SE y SP fueron predictores independientes de AG: RR 0,517 (95% IC: 0,356-0,752), p = 0,001, y RR 1,635 (95% IC 1,070-2,497), p = 0,023. SE y SP también fueron predictores independientes de AR: RR 0,519 (95% IC: 0,349-0,771), p = 0,001, y RR 1,998 (95% IC: 1,281-3,115), p = 0,002. Conclusiones: En varones que cumplen criterios de biopsia prostática se encontró una asociación entre sedentarismo y sobrepeso. El sedentarismo se asoció a mayor riesgo de detección de CP, mientras sedentarismo y sobrepeso incrementaron el riesgo de detección de tumores más agresivos


Objective: To analyze the influence of sedentary (SE) and overweight (OW) in the risk of prostate cancer detection (CP) and aggressiveness. Material and method: We performed prostate biopsy (PB) to 2,408 consecutive male, 5 ARIs untreated, because of elevated serum PSA above 4.0 ng/mL (91%) or suspicious digital rectal examination (9%). In all ultrasound guided PB, 10 cores were obtained plus 2 to 8 additionals, according to age and prostate volume. Physical activity was assessed using a survey (SE vs non-SE) and calculated body mass index (normal vs OW > 25 kg/cm2). The tumor aggressiveness was evaluated according to the Gleason score (high grade «HG»: Gleason> 7) and D’Amico risk (high risk «HR»: T > 3a or PSA > 20 or Gleason score > 7). Results: We found a significant association between SE (52.5%) and OW (72.9%), P < 0.001. The overall PC detection rate was 35.2%. In men with SE it was 36.7% and non-SE 33.6%, P = 0.048. The overall rate of AG tumors was 28.3%, 29.2% in men with SE and 27.1 in non-SE, P = 0.261. The overall rate of AR tumors was 35%, 39.7% in men with SE and 29.4% non-SE, P < 0.001. CP was detected in 38.1% of men with normal BMI and 34.3% in men with OW, P = 0.065. HG tumor rates were 18.1% and 31.4% respectively, P < 0.001 and AR tumor rates were 22.6% and 39.2% respectively, P < 0.001. Binary logistic regression showed that SE was an independent predictor of CP, OR .791 (95% CI: .625-0.989), P = 0.030. SE and OW were independent predictors of HG: OR .517 (95% CI: .356-0.752), P = 0.001, and OR 1.635 (95% CI: 1070-2497), p = 0.023. SE and OW were also independent predictors of HR: OR 0.519 (95% CI 0.349-.771), P = 0.001, and OR 1.998 (95% CI 1.281-3.115), P = 0.002. Conclusions: In men who met criteria for prostate biopsy an association between sedentary and overweight exist. A sedentary lifestyle is associated with increased risk of PC detection while sedentary and overweight were associated with more aggressive tumors


Subject(s)
Humans , Male , Prostatic Neoplasms/diagnosis , Early Detection of Cancer/methods , Neoplasm Staging/methods , Sedentary Behavior , Obesity/complications , Overweight/complications , Risk Factors , Biopsy/methods
9.
Actas Urol Esp ; 38(4): 232-7, 2014 May.
Article in English, Spanish | MEDLINE | ID: mdl-24156935

ABSTRACT

OBJECTIVE: To analyze the influence of sedentary (SE) and overweight (OW) in the risk of prostate cancer detection (CP) and aggressiveness. MATERIAL AND METHOD: We performed prostate biopsy (PB) to 2,408 consecutive male, 5 ARIs untreated, because of elevated serum PSA above 4.0 ng/mL (91%) or suspicious digital rectal examination (9%). In all ultrasound guided PB, 10 cores were obtained plus 2 to 8 additionals, according to age and prostate volume. Physical activity was assessed using a survey (SE vs non-SE) and calculated body mass index (normal vs OW > 25 kg/cm(2)). The tumor aggressiveness was evaluated according to the Gleason score (high grade «HG¼: Gleason > 7) and D'Amico risk (high risk «HR¼: T > 3a or PSA > 20 or Gleason score > 7). RESULTS: We found a significant association between SE (52.5%) and OW (72.9%), P < .001. The overall PC detection rate was 35.2%. In men with SE it was 36.7% and non-SE 33.6%, P = .048. The overall rate of AG tumors was 28.3%, 29.2% in men with SE and 27.1 in non-SE, P = .261. The overall rate of AR tumors was 35%, 39.7% in men with SE and 29.4% non-SE, P < .001. CP was detected in 38.1% of men with normal BMI and 34.3% in men with OW, P = .065. HG tumor rates were 18.1% and 31.4% respectively, P < .001 and AR tumor rates were 22.6% and 39.2% respectively, P < .001. Binary logistic regression showed that SE was an independent predictor of CP, OR .791 (95% CI: .625-.989), P = .030. SE and OW were independent predictors of HG: OR .517 (95% CI: .356-.752), P = .001, and OR 1.635 (95% CI: 1070-2497), p = 0.023. SE and OW were also independent predictors of HR: OR .519 (95% CI .349-.771), P = .001, and OR 1.998 (95% CI 1.281-3.115), P = .002. CONCLUSIONS: In men who met criteria for prostate biopsy an association between sedentary and overweight exist. A sedentary lifestyle is associated with increased risk of PC detection while sedentary and overweight were associated with more aggressive tumors.


Subject(s)
Overweight/complications , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/pathology , Sedentary Behavior , Aged , Aged, 80 and over , Biopsy , Humans , Male , Middle Aged , Prostatic Neoplasms/etiology , Risk Factors
10.
Clin. transl. oncol. (Print) ; 14(10): 715-720, oct. 2012. ilus
Article in English | IBECS | ID: ibc-127006

ABSTRACT

Endometrial cancer (EC) is the most common gynecologic malignancy of the female genital tract and the fourth most common neoplasia in women. In EC, myometrial invasion is considered one of the most important prognostic factors. For this process to occur, epithelial tumor cells need to undergo an epithelial to mesenchymal transition (EMT), either transiently or stably, and to differing degrees. This process has been extensively described in other types of cancer but has been poorly studied in EC. In this review, several features of EMT and the main molecular pathways responsible for triggering this process are investigated in relation to EC. The most common hallmarks of EMT have been found in EC, either at the level of E-cadherin loss or at the induction of its repressors, as well as other molecular alterations consistent with the mesenchymal phenotype-like L1CAM and BMI-1 up-regulation. Pathways including progesterone receptor, TGFβ, ETV5 and microRNAs are deeply related to the EMT process in EC (AU)


Subject(s)
Humans , Female , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/genetics
11.
Int J Androl ; 35(6): 845-859, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22712438

ABSTRACT

The defence of the male reproductive tract against microorganisms is critical for fertilization. The prostate gland has been reported to express several molecules of the innate immune system. However, little information is available about how androgens may modulate host defences within the prostate. We therefore aimed to examine in the rat the expression of the TLR4 system, which is strongly involved in pathogen recognition, and the secretion of the antibacterial substances rBD-1 and SP-D after androgen withdrawal. Immunoblotting and immunocytochemical analysis revealed a time-dependent increase in these molecules after orchiectomy, with epithelial and stromal cells being an important source of prostatic host defence proteins. In view of this, we evaluated the potential improvement in antibacterial ability of the prostatic fluid from orchiectomized animals ex vivo. Only samples from rats at 5 days post-orchiectomy showed a slight inhibition of Escherichia coli growth. Finally, E. coli was inoculated into the ventral prostate of orchiectomized or control rats, with bacterial growth being counted at 5 days after infection. Animals with androgen depletion presented a lower bacterial count, and showed few histological signs of prostatic inflammation compared with controls. In vitro studies confirmed that isolated lipopolysaccharide (LPS)-treated prostatic cells in the absence of testosterone increased SP-D. Moreover, media from these cells showed a higher antimicrobial activity than supernatants from testosterone- and LPS-treated cells. Our findings indicate that testosterone maintains a reduced expression of key elements for innate immunity and diminishes the antibacterial ability of the rat prostate. These data may represent an important mechanism underlying the immunosuppressive activity of testosterone in the gland. However, this immunosuppressive function of androgens is understandable as a means of avoiding uncontrolled immune responses against the haploid male gamete in the reproductive tract.


Subject(s)
Androgen Antagonists/therapeutic use , Bacterial Infections/immunology , Prostate/immunology , Animals , Immunohistochemistry , Male , Prostate/microbiology , Rats , Rats, Wistar
12.
Oncogene ; 31(45): 4778-88, 2012 Nov 08.
Article in English | MEDLINE | ID: mdl-22266854

ABSTRACT

Endometrial carcinoma (EC) is the most frequent among infiltrating tumors of the female genital tract, with myometrial invasion representing an increase in the rate of recurrences and a decrease in survival. We have previously described ETV5 transcription factor associated with myometrial infiltration in human ECs. In this work, we further investigated ETV5 orchestrating downstream effects to confer the tumor the invasive capabilities needed to disseminate in the early stages of EC dissemination. Molecular profiling evidenced ETV5 having a direct role on epithelial-to-mesenchymal transition (EMT). In particular, ETV5 modulated Zeb1 expression and E-Cadherin repression leading to a complete reorganization of cell-cell and cell-substrate contacts. ETV5-promoted EMT resulted in the acquisition of migratory and invasive capabilities in endometrial cell lines. Furthermore, we identified the lipoma-preferred partner protein as a regulatory partner of ETV5, acting as a sensor for extracellular signals promoting tumor invasion. All together, we propose ETV5-transcriptional regulation of the EMT process through a crosstalk with the tumor surrounding microenvironment, as a principal event initiating EC invasion.


Subject(s)
DNA-Binding Proteins/metabolism , Endometrial Neoplasms/metabolism , Epithelial-Mesenchymal Transition , LIM Domain Proteins/metabolism , Signal Transduction , Transcription Factors/metabolism , Cadherins/metabolism , Cell Adhesion/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Nucleus/metabolism , DNA-Binding Proteins/genetics , Endometrial Neoplasms/genetics , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic , Homeodomain Proteins/genetics , Humans , Promoter Regions, Genetic , Protein Transport , Transcription Factors/genetics , Transcription, Genetic , Zinc Finger E-box-Binding Homeobox 1
13.
Prostate ; 70(13): 1402-12, 2010 Sep 15.
Article in English | MEDLINE | ID: mdl-20687213

ABSTRACT

BACKGROUND: Benign prostatic hyperplasia (BPH) represents the most frequent proliferative abnormality of the human prostate. In spite of the well-characterized architectural development of BPH, little is known about the cellular and molecular events that contribute to it. METHODS: We have developed an animal model to evaluate the follow-up of hormone-induced BPH and the analysis of the gene expression associated with BPH. Immunohistochemistry on human patient samples validated the BPH-related molecular alterations. RESULTS: Canine specific Affymetrix microarray analysis performed on sequential biopsies obtained from a beagle dog dynamic model characterized a number of genes altered during the onset of BPH. In addition to the genes involved in calcification, matrix remodeling, detoxification, cell movement, and mucosa protection (MGP, MMP2, TIMP2, ITIH3, GST, MT2A, SULT1A1, FKBP1B, MUC1, STRBP, TFF3), the up-regulation of TGFB3 and CLU indicated a complete adjustment of the transdifferentiation, senescence and apoptosis programs. The up-regulation of Clusterin was validated by RT-qPCR and immunohistochemistry, both in the dog dynamic model and in human samples, further confirming the suitability of the animal model for the study of the molecular alterations associated with BPH. CONCLUSIONS: Transcriptome analysis performed on a dynamic animal model that accurately mimicked the human clinic, allowed us to characterize a gene expression pattern associated with the onset of BPH.


Subject(s)
Apoptosis/genetics , Prostate/metabolism , Prostatic Hyperplasia/genetics , Animals , Cell Differentiation/genetics , Clusterin/genetics , Clusterin/metabolism , Dogs , Gene Expression , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Immunohistochemistry , Male , Oligonucleotide Array Sequence Analysis , Prostate/pathology , Prostatic Hyperplasia/metabolism , Prostatic Hyperplasia/pathology , Reverse Transcriptase Polymerase Chain Reaction
14.
J Steroid Biochem Mol Biol ; 108(3-5): 221-9, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18061438

ABSTRACT

Endometrial carcinoma (EC) is the most common gynecological malignancy in the western world. A widely accepted dualistic model, which has been established on a morphological basis, differentiates EC into two broad categories: Type I oestrogen-dependent adenocarcinoma with an endometrioid morphology and Type II non-oestrogen-dependent EC with a serous papillary or clear cell morphology. Molecular genetic evidence indicates that endometrial carcinoma, as described in other malignancies, likely develops as the result of a stepwise accumulation of alterations in cellular regulatory pathways, such as oncogene activation and tumor suppressor gene inactivation, which lead to dysfunctional cell growth. These molecular alterations appear to be specific in Type I and Type II cancers. In type I endometrioid endometrial cancer, PTEN gene silencing in conjunction with defects in DNA mismatch repair genes, as evidenced by the microsatellite instability phenotype, or mutations in the K-ras and/or beta-catenin genes, are recognized major alterations, which define the progression of the normal endometrium to hyperplasia, to endometrial intraepithelial neoplasia, and then on to carcinoma. In contrast, Type II cancers show mutations of TP53 and Her-2/neu and seem to arise from a background of atrophic endometrium. Nevertheless, despite the great effort made to establish a molecularly-based histological classification, the following issues must still be clarified: what triggers the tumor cells to invade the myometrium and what causes vascular or lymphatic dissemination, finally culminating in metastasis? RUNX1, a transcription factor, was recently identified as one of the most highly over-expressed genes in a microarray study of invasive endometrial carcinoma. Another candidate gene, which may be associated with an initial switch to myometrial infiltration, is the transcription factor ETV5/ERM. These studies, as well as those conducted for other genes possibly involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, could help in understanding the differences in the biology and the clinical outcome among histological types.


Subject(s)
Carcinoma, Endometrioid/genetics , Endometrial Neoplasms/pathology , Adenocarcinoma/pathology , Adenocarcinoma, Clear Cell/pathology , Core Binding Factor Alpha 2 Subunit/genetics , Cystadenocarcinoma, Papillary/pathology , DNA Mismatch Repair , Female , Genes, erbB-2/genetics , Genes, p53/genetics , Genes, ras/genetics , Humans , Microsatellite Instability , Neoplasms, Hormone-Dependent/pathology , Oncogenes/genetics , PTEN Phosphohydrolase/genetics , Receptors, Estrogen/genetics , Receptors, Progesterone/genetics
15.
Clin Transl Oncol ; 9(5): 272-7, 2007 May.
Article in English | MEDLINE | ID: mdl-17525037

ABSTRACT

Endometrial carcinoma is the most common gynaecological malignancy in the western world and the most frequent among infiltrating tumours of the female genital tract. Despite the characterisation of molecular events associated with the development of endometrial carcinoma, those associated with the early steps of infiltration and invasion in endometrial cancer are less known. Deep myometrial invasion correlates with more undifferentiated tumours, lymph-vascular invasion, node affectation and decreased global survival. In this review we present an overview of the molecular pathology of myometrial infiltration that defines the initial steps of invasion in endometrial cancer. Down-regulation of E-cadherin as a main player of epithelial to mesenchymal transition, as well as modifications on other molecules involved in cell-cell contacts, render cells with a migratory phenotype. In addition, altered signalling pathways and transcription factors associate with myometrial invasion, histologic grade and metastasis.


Subject(s)
Endometrial Neoplasms/etiology , Endometrial Neoplasms/pathology , Cell Adhesion Molecules/physiology , Endometrial Neoplasms/genetics , Female , Gene Expression , Humans , Neoplasm Invasiveness
16.
Clin. transl. oncol. (Print) ; 9(5): 272-277, mayo 2007. ilus
Article in English | IBECS | ID: ibc-123307

ABSTRACT

Endometrial carcinoma is the most common gynaecological malignancy in the western world and the most frequent among infiltrating tumours of the female genital tract. Despite the characterisation of molecular events associated with the development of endometrial carcinoma, those associated with the early steps of infiltration and invasion in endometrial cancer are less known. Deep myometrial invasion correlates with more undifferentiated tumours, lymph-vascular invasion, node affectation and decreased global survival. In this review we present an overview of the molecular pathology of myometrial infiltration that defines the initial steps of invasion in endometrial cancer. Down-regulation of E-cadherin as a main player of epithelial to mesenchymal transition, as well as modifications on other molecules involved in cell-cell contacts, render cells with a migratory phenotype. In addition, altered signalling pathways and transcription factors associate with myometrial invasion, histologic grade and metastasis (AU)


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No disponible


Subject(s)
Humans , Female , Endometrial Neoplasms/etiology , Endometrial Neoplasms/pathology , Gene Expression Profiling , Cell Adhesion Molecules/physiology , Endometrial Neoplasms/genetics , Gene Expression , Endometrium/pathology
18.
Biomed Tech (Berl) ; 50(11): 371-4, 2005 Nov.
Article in German | MEDLINE | ID: mdl-16370151

ABSTRACT

The German Artificial Sphincter System GASS consists of a support ring which includes a fluid reservoir on the outer side and an occlusive cuff on the inner side. The cuffs are designed as polyurethane hollow bodies with a pre-determined inflation volume and are connected to an integrated piezo micropump/valve unit. To evaluate the threshold of continence, the GASS was placed around the anorectal junction via a perineal approach in one mini pig. The novel cuff design reduces the occlusion pressure and allows low compression volumes. Low operating pressures indicate a minor risk of ischemia injury of the bowel. The operation time is estimated at about 6 days with no recharging of the battery. The novel remote controlled GASS is a highly integrated prosthesis for placement around the anal canal or lower rectum and is effective in restoring continence for liquids and solids in vitro and in vivo.


Subject(s)
Anal Canal/physiopathology , Artificial Organs , Fecal Incontinence/rehabilitation , Prostheses and Implants , Swine, Miniature , Telemetry/instrumentation , Therapy, Computer-Assisted/instrumentation , Anal Canal/surgery , Animals , Equipment Failure Analysis , Fecal Incontinence/surgery , Germany , Prosthesis Design , Swine , Systems Integration , Treatment Outcome
19.
Biomed Tech (Berl) ; 49(10): 274-8, 2004 Oct.
Article in German | MEDLINE | ID: mdl-15566076

ABSTRACT

No highly integrated sphincter prosthesis for therapy of major fecal incontinence exists. Therefore, we developed a novel neosphincter, made of polyurethane. The GASS consists of a support ring (SR) which includes a fluid reservoir, fixed on the outer diameter of the SR, and a multi-chamber occluding cuff (C(int)) on the inside diameter. The total inflation volume of C(int) is about 23 cc. The integrated micropump based on piezotechnology measures 30x13x1 mm3 (flowrate 1.4 cc/min, max. backpressure 40,000 Pa) . GASS was evaluated around the external sphincter of isolated porcine anal canals. The threshold of continence was defined as the inflating volume which water ceased to leak through the area occluded by C(int) under an induced rectal pressure of 150 cm H2O. Minimal filling volumes maintained continence for liquids against high luminal pressures. A low intraanal resting pressure (delta p(anal)) induced by activated GASS indicates a little risk of ischemic injury of the anal canal in vivo (median delta p(anal) 24.1 mm hg:15 cc vs 46.9 mm hg:21 cc). In summary, a highly integrated and efficient high-tech neosphincter for the therapy of major fecal incontinence could be realized.


Subject(s)
Anal Canal/physiopathology , Anal Canal/surgery , Artificial Organs , Fecal Incontinence/physiopathology , Fecal Incontinence/surgery , Animals , Equipment Failure Analysis , Fecal Incontinence/rehabilitation , In Vitro Techniques , Prosthesis Design , Swine
20.
Comput Biol Med ; 34(4): 307-22, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15121002

ABSTRACT

This paper describes a revision of the Hill-type muscle model so that it will describe the chemo-mechanical energy conversion process (energetic) and the internal-element stiffness variation (viscoelastic) during a skeletal muscle isometric force twitch contraction. The derivation of this energetic-viscoelastic model is described by a first-order linear ordinary differential equation with constant energetic and viscoelastic coefficients. The model has been implemented as part of a biomimetic model, which describes the excitation-contraction coupling necessary to drive the energetic-viscoelastic model. Finally, the energetic-viscoelastic model is validated by comparing its isometric force-time profile with that of various muscles reported in the literature.


Subject(s)
Isometric Contraction/physiology , Models, Biological , Muscle, Skeletal/physiology , Calcium/metabolism , Cell Membrane Permeability/physiology , Computer Simulation , Humans
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