Cellular origin and differentiation of renal carcinomas. A fluorescence microscopic study with kidney-specific antibodies, antiintermediate filament antibodies, and lectins

Frozen sections of human renal carcinomas were studied in indirect immunofluorescence using antibodies against intermediate filaments of cytokeratin, desmin and vimentin type, and against proximal tubular brush border and distal tubular Tamm-Horsfall glycoprotein antigens, as well as with fluorochrome-labeled lectins in an attempt to study the origin and stage of differentiation of renal carcinomas. Eighty per cent of the renal carcinomas expressed the brush border antigens, whereas the Tamm-Horsfall glycoprotein could not be found. Antibodies against epidermal cytokeratins reacted only with collecting ducts in normal kidney, whereas antibodies against cytokeratins of Madin-Darby canine kidney epithelial cell line also reacted with glomerular and tubular epithelium. In 93% of the carcinomas tumor cells showed reactivity with both types of antikeratin antibodies. Vimentin, the cytoskeletal protein of mesenchymal cells, was present in the carcinoma cells of 53% of the tumors, although it was not present in normal tubular epithelium. Moreover, vimentin was expressed together with cytokeratin in the carcinoma cells in 57% of the keratin-positive samples as judged by double immunostaining, whereas the muscle type of intermediate filament protein, desmin, was not seen in the malignant cells. Binding sites for Lotus tetragonolobus agglutinin and soybean agglutinin, normally present in the cells of proximal tubules, were lacking or only faintly detectable in the neoplastic cells. Dolichos biflorus agglutinin, normally present in collecting ducts, was not detected in the tumors. The results show that most renal carcinomas express cytokeratin antigens as a sign of their epithelial origin and also show characteristics of proximal tubular cells. On the other hand, the results indicate that lectin-binding sites typical for normal differentiated tubular cells are profoundly modified in renal carcinomas. Ulex europaeus agglutinin did not bind to the malignant cells but decorated the endothelial cells of the tumors.     

Gene expression signatures differentiate uterine endometrial stromal sarcoma from leiomyosarcoma

ObjectiveEndometrial stromal sarcoma (ESS) and leiomyosarcoma (LMS) are the two most common uterine sarcomas, but both are rare tumors. The aim of the present study was to compare the global gene expression patterns of ESS and LMS.MethodsGene expression profiles of 7 ESS and 13 LMS were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry.ResultsUnsupervised hierarchical clustering using all 54,675 genes in the array separated ESS from LMS samples. We identified 549 unique probes that were significantly differentially expressed in the two malignancies by greater than 2-fold with 1% FDR cutoff using one-way ANOVA with Benjamini–Hochberg correction, of which 336 and 213 were overexpressed in ESS and LMS, respectively. Genes overexpressed in ESS included SLC7A10, EFNB3, CCND2, ECEL1, ITM2A, NPW, PLAG1 and GCGR. Genes overexpressed in LMS included CDKN2A, FABP3, TAGLN, JPH2, GEM, NAV2 and RAB23. The top 100 genes overexpressed in LMS included those coding for myosin light chain and caldesmon, but not the genes coding for desmin or actin. CD10 was not overexpressed in ESS. Results for selected genes were validated by quantitative real-time PCR and immunohistochemistry.ConclusionsWe present the first study in which gene expression profiling was shown to distinguish between ESS and LMS. The molecular signatures unique to each of these malignancies may aid in expanding the diagnostic battery for their differentiation, and may provide a molecular basis for prognostic studies and therapeutic target discovery.     

Mental health as perceived by persons with mental disorders – an interpretative phenomenological analysis study

In this interpretative phenomenological analysis study, we explored how persons with mental disorders perceive mental health. Adapting a salutogenic theoretical framework, 12 former inpatients were interviewed. The analysis revealed experiences of mental health as a movement, like walking up and down a staircase. Perceived mental health is expressed both verbally in an everyday language and through body language. Mental health is an aspect of being that is always present and which is nourished by four domains of life: the emotional; physical; social and spiritual domains. Mental health is experienced in everyday life as a sense of energy, and as more or less wellbeing. Exploring persons' meanings of mental health from a subjective perspective can extend the knowledge base that can be used in mental health promotion strategies.     

Root length in transplanted premolars

The objectives of the present prospective longitudinal study were to establish the survival and success rates for premolars with partly developed roots transplanted according to a set protocol, and to analyze the effect of varying pre‐surgery root development on final root length. Standardized periapical radiographs of 132 consecutively transplanted premolars were obtained at predetermined intervals over a 4‐year follow‐up period. Survival and success rates were calculated on the basis of presence of teeth and recording of defined radiological variables, respectively. Final root length was compared to normative metric data for root morphology. From the total sample, 54 patients with 68 transplanted premolars suitable for analysis of root growth relative to initial root length were identified, and divided into subsamples according to root length pre‐transplantation. Survival rates were 100% after 1, 2, and 3 years, and 98.6% 4 years post‐transplantation. The success rates were 92.9%, 92.8%, 89%, and 90.5% in subsamples collected 1, 2, 3, and 4 years after transplantation, respectively. The transplants obtained on average 78% of normative root length, and by dichotomizing the transplanted teeth in subsamples with ‘short’ and ‘long’ roots pre‐surgery, similar final root lengths were observed even if ‘short’ roots had the greatest increase. Very early transplantation (roots <7 mm), however, tended to result in short final root length. It is concluded that the success and survival rates were comparable to results obtained in similar studies. Initial root length was a significant predictor of root length increase. Transplanting teeth with short roots is to risk short final root length.     

Extraoral vertical subcondylar osteotomy with rigid fixation for correction of mandibular prognathism. Comparison with bilateral sagittal split osteotomy and surgical technique

PurposeThe aim was to compare outcome after extraoral vertical subcondylar osteotomy (EVSO) with rigid fixation and bilateral sagittal split osteotomy (BSSO) for correction of mandibular prognathism. The objectives were to examine treatment factors, postoperative results, and long-term stability. The surgical technique for EVSO is presented in detail.Subjects and methodsLateral cephalograms and information from patient files of 65 consecutively operated patients with EVSO and 65 matching patients operated with BSSO were analyzed preoperatively, postoperatively, after 6 months and 3 years.ResultsNo clinically significant differences were observed in long-term stability. The retromandibular scar inferior to the earlobe after EVSO was on average 25 mm long and 1 mm wide, and was of no concern for most of the patients. Normal or near normal sensation to the lower lip/chin was reported by half of the BSSO patients at the 3-year follow-up.ConclusionBecause no major differences in outcome were observed, EVSO with rigid fixation may be considered as a viable alternative if it is important to avoid alterations in sensation, whereas BSSO may be preferred if retromandibular scar is of concern.     

The NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction (NORDISTEMI)

Objectives. Thrombolysis is the treatment of choice for patients with ST-elevation myocardial infarction (STEMI) living in rural areas with long transfer delays to percutaneous coronary intervention (PCI). This trial compares two different strategies following thrombolysis: to transfer all patients for immediate coronary angiography and intervention, or to manage the patients more conservatively. Design. The NORwegian study on DIstrict treatment of STEMI (NORDISTEMI) is an open, prospective, randomized controlled trial in patients with STEMI of less than 6 hours of duration and more than 90 minutes expected time delay to PCI. A total of 266 patients will receive full-dose thrombolysis, preferably prehospitally, and then be randomized to either strategy. Our primary endpoint is the one year combined incidence of death, reinfarction, stroke or new myocardial ischaemia. The study is registered with ClinicalTrials.gov, number NCT00161005. Results. By April 2006, 109 patients have been randomized. Thrombolysis has been given prehospitally to 52% of patients. The median transport distance from first medical contact to catheterization laboratory was 155 km (range 90–396 km). Results of the study are expected in 2008.

Trial registration: ClinicalTrials.gov identifier: NCT00161005.     

Repeated image analyses improves accuracy in assessing arterial flow-mediated dilatation

Objectives. A high degree of variability has been reported regarding the ultrasound-based assessment of flow-mediated dilatation. We wanted to investigate the variability and find out how it might be reduced most efficiently. Design. Brachial artery flow-mediated dilatation was measured by high-resolution ultrasound in 22 healthy adults on two consecutive days. Two observers analysed all images twice. The total variance was split into variance components and estimated hierarchically using the method of restricted maximum likelihood. Results. The relative proportional contributions from intraobserver (residual), interobserver, interpatient and interday variance components, with percentage dilatation as outcome variable, were 0.41, 0.18, 0.25, and 0.15, respectively. Conclusions. The major source of variability when assessing flow-mediated dilatation was found to be intraobserver variability. The simplest way to reduce total variability is for the observer to average results from repeated image analyses. We suggest that three repetitions are sufficient. This will reduce the total variance by 30%.