TERT-Regulation and Roles in Cancer Formation.

Telomerase reverse transcriptase (TERT) is a catalytic subunit of telomerase. Telomerase complex plays a key role in cancer formation by telomere dependent or independent mechanisms. Telomere maintenance mechanisms include complex TERT changes such as gene amplifications, TERT structural variants, TERT promoter germline and somatic mutations, TERT epigenetic changes, and alternative lengthening of telomere. All of them are cancer specific at tissue histotype and at single cell level. TERT expression is regulated in tumors via multiple genetic and epigenetic alterations which affect telomerase activity. Telomerase activity via TERT expression has an impact on telomere length and can be a useful marker in diagnosis and prognosis of various cancers and a new therapy approach. In this review we want to highlight the main roles of TERT in different mechanisms of cancer development and regulation.

Sub-endocardial and sub-epicardial measurement of myocardial blood flow using 13NH3 PET in man.

BACKGROUND: This study examined whether measuring myocardial blood flow (MBF) in the sub-endocardial (SEN) and sub-epicardial (SEP) layers of the left ventricular myocardium using 13NH3 positron emission tomography (PET) and an automated procedure gives reasonable results in patients with known or suspected coronary artery disease (CAD). METHODS: Resting and stress 13NH3 dynamic PET were performed in 70 patients. Using ≥ 70% diameter stenosis in invasive coronary angiography (ICA) to identify significant CAD, we examined the diagnostic value of SEN- and SEP-MBF, and coronary flow reserve (CFR) vs. the corresponding conventional data averaged on the whole wall thickness. RESULTS: ICA demonstrated 36 patients with significant CAD. Their global stress average [1.61 (1.26, 1.87) mL·min-1·g-1], SEN [1.39 (1.2, 1.59) mL·min-1·g-1] and SEP [1.22 (0.96, 1.44) mL·min-1·g-1] MBF were significantly lower than in the 34 no-CAD patients: 2.05 (1.76, 2.52), 1.72 (1.53, 1.89) and 1.46 (1.23, 1.89) mL·min-1·g-1, respectively, all P < .005. In the 60 CAD vs. the 150 non-CAD territories, stress average MBF was 1.52 (1.10, 1.83) vs. 2.06 (1.69, 2.48) mL·min-1·g-1, SEN-MBF 1.33 (1.02, 1.58) vs. 1.66 (1.35, 1.93) mL·min-1·g-1, and SEP-MBF 1.07 (0.80, 1.29) vs. 1.40 (1.12, 1.69) mL·min-1·g-1, respectively, all P < .05. Using receiver operating characteristics analysis for the presence of significant CAD, the areas under the curve (AUC) were all significant (P < .0001 vs. AUC = 0.5) and similar: stress average MBF = 0.79, SEN-MBF = 0.75, and SEP-MBF = 0.73. AUC was 0.77 for the average CFR, 0.75 for SEN, and 0.70 for SEP CFR. The stress transmural perfusion gradient (TPG) AUC (0.51) was not significant. However, stress TPG was significantly lower in segments subtended by totally occluded arteries vs. those subtended by sub-total stenoses: 1.10 (0.86, 1.33) vs. 1.24 (0.98, 1.56), respectively, P < .005. CONCLUSION: Automatic assessment of SEN- and SEP-MBF (and CFR) using 13NH3 PET gives reasonable results that are in good agreement with the conventional average whole wall thickness data. Further studies are needed to examine the utility of layer measurements such as in patients with hibernating myocardium or microvascular disease.

Novel 3D heart left ventricle muscle segmentation method for PET-gated protocol and its verification.

OBJECTIVE: The aim of this study was to propose and verify a universal method of left ventricular myocardium segmentation, able to operate on heart gated PET data with different sizes, shapes and uptake distributions. The proposed method can be classified as active model method and is based on the BEAS (B-spline Explicit Active Surface) algorithm published by Barbosa et al. The method was implemented within the Pmod PCARD software package. Method verification by comparison with reference software and phantom data is also presented in the paper. METHODS: The proposed method extends the BEAS model by defining mechanical features of the model: tensile strength and bending resistance. Formulas describing model internal energy increase during its stretching and bending are proposed. The segmentation model was applied to the data of 60 patients, who had undergone cardiac gated PET scanning. QGS by Cedars-Sinai and ECTb by Emory University Medical Centre served as reference software for comparing ventricular volumes. The method was also verified using data of left ventricular phantoms of known volume. RESULTS: The results of the proposed method are well correlated with the results of QGS (slope: 0.841, intercept: 0.944 ml, R2: 0.867) and ECTb (slope: 0.830, intercept: 2.109 ml, R2: 0.845). The volumes calculated by the proposed method were very close to the true cavity volumes of two different phantoms. CONCLUSIONS: The analysis of gated PET data by the proposed method results in volume measurements comparable to established methods. Phantom experiments demonstrate that the volume values correspond to the physical ones.

[The skin incisions (blow holes) for treatment of massive subcutaneous emphysema]. / Blow holes ­ metoda leczenia masywnej odmy podskórnej .

BACKGROUND: Subcutaneous emphysema (SE) is rarely life-threatening, although it may create significant discomfort to patients. It may impede eye opening, movement of the limbs and sometimes causes stridor and respiratory distress. We describe two cases of SE, in which small incisions in the skin helped to relieve symptoms. CASE REPORTS: Case 1. A 64-year-old male was admitted to ITU, having been intubated after blunt chest trauma during a traffic accident. Initial presentation included respiratory failure, massive SE of the face, neck and chest, and fractured ribs with bilateral pneumothorax and bilateral lung contusion. Ventilation with BiPAP with 15 cm H2O PEEP was commenced and a right chest drain was inserted. This resulted in rapid improvement of gas exchange, but SE became progressively larger. On the second day, several 2 cm skin incisions were made bilaterally in the subclavicular regions; immediately a loud hiss of escaping air was heard and the patient's condition improved rapidly. He was extubated after seven days and made a full recovery. Case 2. A 42-yr-old male was admitted to ITU three days after a street fight because of rapidly progressing SE, extending to the head, neck, chest, abdomen and legs. He was suffering from pneumomediastinum, pneumopericardium, and broken ribs, hyoid bone and Th10 spinous process. An emergency tracheostomy was performed and blow holes were made in both subclavicular regions. This resulted in rapid improvement and he was discharged home after two weeks in hospital. DISCUSSION AND CONCLUSION: Several methods of treatment for severe SE have been described, including pleural drainage, subcutaneous insertion of pig-tail drains, iv cannulas or large bore drains. The method described, albeit not always successful, is simple and can be applied in every setting.

[Cardiac arrest in chronic metabolic alkalosis due to sodium bicarbonate abuse]. / Zatrzymanie krazenia w przebiegu zasadowicy metabolicznej i zaburzen elektrolitowych u osoby spozywajacej sode oczyszczona.

BACKGROUND: Moderate metabolic alkalosis has not been considered as a life-threatening situation by many authors, but when it persists and pH increases above 7.65, the situation may become critical. CASE REPORT: We present a case of a 61-yr-old alcoholic male patient, who had been consuming approximately 200 g of sodium bicarbonate daily for twenty years, due to persisitent heartburn and abdominal pains. The patient was admitted to the ITU after home cardiac arrest and resuscitation. On admission he was unconscious and in respiratory distress, with a GCS of 5. Blood gases revealed that his pH was 7.64, HCO3 44 mmol L(-1), K+ 2.4 mmol L(-1)l, Cl- 44 mmol L(-1), and lactate concentration over 15 mmol L(-1). He was treated with controlled hypercapnia, up to a PaCO2 of 63 mm Hg, sedation, and administration of a large amount of chloride (864 mmol during the first day). The patient regained consciousness after 48 h, was extubated and transferred to the internal medicine department where he died 3 days later. DISCUSSION: Chronic alkali abuse can lead to various metabolic disturbances, neurologic disturbances and cardiovascular compromise. In the described case, the exact cause of cardiac arrest remained unknown, but may have been caused by alkalosis combined with hypoxia, hypokalemia and poor general condition. The extreme metabolic alkalosis (pH 7.8) could also have been enhanced by the administration of i.v. sodium bicarbonate during resuscitation. The treatment of choice in such cases should consist of vigorous chloride containing fluid resuscitation, ammonium chloride and hemodialysis.