Cyclooxygenase-2 expression in primary Merkel cell carcinoma

BACKGROUND: Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine skin tumor. The typical course of MCC is rapid progression of the primary tumor and metastatic dissemination to the regional lymph nodes. Thus far, no biological, prognostic marker has been established for this aggressive neoplasm. Cyclooxygenase-2 (Cox-2) is undetectable in most normal tissues, but it is induced in various cell types by inflammation and carcinogenesis. Although the expression and function of Cox-2 have been studied extensively in several carcinomas, little is known about Cox-2 expression in neuroendocrine carcinomas. The aim of the present report was to study Cox-2 expression in MCC and find out whether this expression correlates with outcome. METHODS: Immunohistochemical analysis for Cox-2 was performed on 22 primary MCC samples. RESULTS: Almost 70% of the samples showed positive staining. Protein expression of Cox-2 was sparse and low in intensity. We found a tendency for enhanced Cox-2 expression in tumors located in sun-exposed areas. Cox-2 expression had no significant statistical correlation with clinical parameters. CONCLUSIONS: MCC expresses Cox-2 in low levels, and the expression did not prove to be a prognostic factor. Furthermore, the low expression suggests that the primary treatment option for MCC is not therapeutic inhibition of Cox-2.     

Differential results between self-report and interview-based ratings of risk symptoms of psychosis

Aim: Assessing potential risk of developing psychosis has gained growing attention in recent literature. The selection of suitable assessment methods is the central question for this research endeavour. Whereas prodromal detection instruments are mostly interview‐based instruments, there are short screening instruments for self‐report use. Methods: Difference in psychosis risk scores was tested between self‐report results and interview results, with risk symptoms of psychosis included in PROD screening instrument. Subjects were recruited by an early intervention team in Finland. Results: There was a significant difference between psychosis risk scores based on self‐report versus interview in a sample of adolescents (n = 87; P < 0.001). Conclusions: Results suggest that when using screening instruments, risk scores and risk status may vary by the method the information is collected. Checking self‐report results by an additional interview is recommended for both clinical and scientific uses.     

Brain anomalies in 121 children with non-syndromic single suture craniosynostosis by MR imaging

IntroductionThe aim of this study was to evaluate prevalence of intracranial abnormalities in children with non-syndromic single suture craniosynostosis scheduled for cranial vault remodelling surgery using pre-operative magnetic resonance imaging.Patients and methodsA retrospective analysis of brain magnetic resonance imaging studies of 129 non-syndromic single suture craniosynostosis children undergoing craniofacial surgery between January, 2004–October, 2010 was conducted. Statistical analysis was performed for child, maternal and sibling related predisposing factors for abnormal brain magnetic resonance imaging findings.The mean age of these 121 patients at the time of imaging was 21.6 months. The majority, 78% were males and 74% of the patients were scaphocephalic.ResultsIn 18 (15%) patients abnormal brain findings were noted. The most common finding was Chiari 1 malformation in 11 (9%). Chiari 1 malformation comprised over half (61%) of the brain anomalies identified. None of these findings required any additional surgical procedures. None of the statistical analysis reached statistical significance.ConclusionsBrain anomalies in connection with non-syndromic single suture craniosynostosis patients seem to be a coincidental event. We did not establish any specific craniosynostosis form to be regularly associated with abnormal brain magnetic resonance imaging findings. The routine use of pre-operative magnetic resonance imaging in non-syndromic single suture craniosynostosis patients seems to be of limited value in the search for associated intracranial malformations necessitating additional interventions.     

Bcl-2 expression indicates better prognosis of Merkel cell carcinoma regardless of the presence of Merkel cell polyomavirus

Merkel cell carcinoma (MCC) is an aggressive dermal tumour of neuroendocrine origin. The recently found Merkel cell polyomavirus (MCV) integrates clonally in the tumour genome, which suggests an important role in the pathogenesis of the disease. Previous small-scale studies have detected anti-apoptotic protein bcl-2 in 80?% of MCC tumours, but its correlation to the prognosis of MCC remains controversial. Our aim was to clarify the correlation of immunohistochemical expression of bcl-2 to MCV presence and MCC prognosis. We analyzed 116 primary MCC specimens with corresponding clinical data by immunohistochemistry for bcl-2. The presence of MCV DNA had been analyzed by quantitative PCR for 108 tumours. The correlations were analyzed statistically. Of the primary MCC samples, 85?% were bcl-2 positive. No significant differences in MCV DNA occurred between the bcl-2-positive and bcl-2-negative tumours. Local and systemic metastasis was more common in patients with bcl-2 negative tumours (33?%) than in patients with bcl-2-positive tumours (12?%; p?=?0.04) at the time of diagnosis. The mean overall survival was higher in patients with bcl-2-positive tumours than of those with negative tumours (mean survival 1,814?days (5.0?years) vs. 769?days (2.1?years), p?=?0.01). Bcl-2 positivity indicates better clinical stage at the time of diagnosis and a longer survival in MCC.     

Evaluation of Ki-67 as a histological index of burn damage in a swine model

Histological diagnosis of burn depth lacks consensus. The purpose of this study was to determine whether Ki-67, a cell proliferation marker, provides an index of integument viability after burn injury. Induction of thermal burn injuries (3, 12, 20, 30, 75, 90, and 120 seconds) were made with a brass rod heated to 100°C on the dorsal trunk of the swine. Controls were created with a brass rod heated to 37.5°C. Four 6-mm biopsies were obtained from each site for histological analysis of Ki-67. Biopsies were taken at the following times postinjury: 1, 12, 24, 36, 48, 72, and 96 hours. The results illustrate a characteristic Ki-67 nuclear staining in the basal layer of the epidermis and in the hair follicle. With increasing thermal injury, the nuclei of the cells changed morphology: condensing, fragmenting, and elongating. The uniqueness of the labeling index was to include only morphologically intact nuclei as having capacity to proliferation. Quantitative analysis showed a reduction in the mean number of Ki-67-positive cells, suggesting a reduced regenerative capacity. This study supports using this index as a means of performing histology for burn depth analysis. In future studies, determining viability of partial-thickness burns will require multiple histological markers such as Ki-67 in addition to hematoxylin and eosin staining.     

Insulin Receptor β-Subunit Haploinsufficiency Impairs Hippocampal Late-Phase LTP and Recognition Memory

The insulin receptor (IR) is a protein tyrosine kinase playing a pivotal role in the regulation of peripheral glucose metabolism and energy homoeostasis. IRs are also abundantly distributed in the cerebral cortex and hippocampus, where they regulate synaptic activity required for learning and memory. As the major anabolic hormone in mammals, insulin stimulates protein synthesis partially through the activation of the PI3K/Akt/mTOR pathway, playing fundamental roles in neuronal development, synaptic plasticity and memory. Here, by means of a multidisciplinary approach, we report that long-term synaptic plasticity and recognition memory are impaired in IR ??-subunit heterozygous mice. Since IR expression is diminished in type-2 diabetes as well as in Alzheimer??s disease (AD) patients, these data may provide a mechanistic link between insulin resistance, impaired synaptic transmission and cognitive decline in humans with metabolic disorders.     

Merkel cell carcinoma - a population-based epidemiological study in Finland with a clinical series of 181 cases

BackgroundMerkel cell carcinoma (MCC) is a rare malignancy of the skin, and its incidence is reported to be rising. The purpose of this study was to calculate its incidence and survival ratios, and to describe the clinical characteristics of Merkel cell carcinoma patients in Finland.MethodsWe calculated the incidence of MCC based on data from the Finnish Cancer Registry. In addition, patient files from hospitals and primary health care centres were reviewed for detailed data on the treatment and disease recurrence of 181 patients diagnosed with MCC in Finland during 1983–2004, and relative survival ratios were calculated for them.ResultsThe incidence (per 100,000) of MCC in Finland in 1989–2008 was 0.11 for men and 0.12 for women, adjusted for age to the world standard population. The mean age at diagnosis was 76 years (range 27–100), and 69% of the patients were women. The most common site of the primary tumour was the head and neck (53%). No extra benefit was gained from a wide surgical margin (⩾2 cm) compared to a margin of 0.1–0.19 cm, but an intralesional excision was more often associated with local recurrence. None of the patients with Stage I–II disease who had received postoperative radiotherapy to the tumour bed had a local recurrence. The 5-year relative survival ratio amongst men was 36% (95% confidence interval 20–54%), and amongst women 69% (56 to −82%).ConclusionsMCC is a rare disease in Finland, with incidence rates similar to those in the other Nordic countries. Our results support the view that complete excision with clear margins and post operative radiotherapy decrease local recurrences.     

The effect of dimethyl sulfoxide (DMSO) on dentin bonding and nanoleakage of etch-and-rinse adhesives

Objective

The objective was to examine the effect of a solvent dimethyl sulfoxide (DMSO) on resin–dentin bond durability, as well as potential functional mechanisms behind the effect.

Methods

Microtensile bond strength (μTBS) was evaluated in extracted human teeth in two separate experiments. Dentin specimens were acid-etched and assigned to pre-treatment with 0.5 mM (0.004%) DMSO as additional primer for 30 s and to controls with water pre-treatment. Two-step etch-and-rinse adhesive (Scotchbond 1XT, 3M ESPE) was applied and resin composite build-ups were created. Specimens were immediately tested for μTBS or stored in artificial saliva for 6 and 12 months prior to testing. Additional immediate and 6-month specimens were examined for interfacial nanoleakage analysis under SEM. Matrix metalloproteinase (MMP) inhibition by DMSO was examined with gelatin zymography. Demineralized dentin disks were incubated in 100% DMSO to observe the optical clearing effect.

Results

The use of 0.5 mM DMSO had no effect on immediate bond strength or nanoleakage. In controls, μTBS decreased significantly after storage, but increased significantly in DMSO-treated group. The control group had significantly lower μTBS than DMSO-group after 6 and 12 months. DMSO also eliminated the increase in nanoleakage seen in controls. 5% and higher DMSO concentrations significantly inhibited the gelatinases. DMSO induced optical clearing effect demonstrating collagen dissociation.

Significance

DMSO as a solvent may be useful in improving the preservation of long-term dentin–adhesive bond strength. The effect may relate to dentinal enzyme inhibition or improved wetting of collagen by adhesives. The collagen dissociation required much higher DMSO concentrations than the 0.5 mM DMSO used for bonding.