Quantitative methylation-specific polymerase chain reaction gene patterns in urine sediment distinguish prostate cancer patients from control subjects.

PURPOSE: Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of prostate cancers and is a promising marker for cancer detection. We sought to develop a test for prostate cancer based on a quantitative methylation-specific polymerase chain reaction (QMSP) of multiple genes in urine sediment DNA. PATIENTS AND METHODS: We tested urine sediment DNA for aberrant methylation of nine gene promoters (p16INK4a, p14(ARF), MGMT, GSTP1, RARbeta2, CDH1 [E-cadherin], TIMP3, Rassf1A, and APC) from 52 patients with prostate cancer and 21 matched primary tumors by quantitative fluorogenic real-time polymerase chain reaction. We also analyzed urine sediments from 91 age-matched individuals without any history of genitourinary malignancy as controls. RESULTS: Promoter hypermethylation of at least one of the genes studied was detected in urine samples from all 52 prostate cancer patients. Urine samples from the 91 controls without evidence of genitourinary cancer revealed no methylation of the p16, ARF, MGMT, and GSTP1 gene promoters, whereas methylation of RARbeta2, TIMP3, CDH1, Rassf1A, and APC was detected at low levels. CONCLUSION: Overall, methylation found in urine samples matched the methylation status in the primary tumor. A combination of only four genes (p16, ARF, MGMT, and GSTP1) would theoretically allow us to detect 87% of prostate cancers with 100% specificity. Our data support further development of the noninvasive QMSP assay in urine DNA for early detection and surveillance of prostate cancer.     

Recurrent Left Ventricular Apical Ballooning Syndrome in a Patient with Pheochromocytoma

Transient left ventricular apical ballooning syndrome is characterized by reversible left ventricular wall motion abnormalities, chest pain or dyspnea, ST-segment elevation, and mild elevation of cardiac enzyme levels in the absence of obstructive coronary artery disease. The pathophysiology of the syndrome is still unknown. The probable mechanism is supposed to be a catecholamine discharge. We report the case of a 66-year-old woman with recently diagnosed pheochromocytoma who presented with chest pain and ST-segment elevation. Coronary angiography revealed normal coronaries and apical dyskinesia at ventriculography. A similar episode of chest pain occurred 4 years ago with same angiographic findings and reversible inferobasal akinesia. In-hospital course was uneventful and the patient was discharged from the hospital 4 days later with treatment of aspirin 1 × 100 mg, metoprolol 1 × 50 mg, lisinopril 1 × 10 mg, and atorvastatin 1 × 20 mg. At 2 years follow-up after the event, the patient remained asymptomatic.     

Aromatase cytochrome P450 enzyme expression in prolactinomas and its relationship to tumor behavior

The aim of the study was to evaluate the presence of aromatase cytochrome P450 enzyme (P450AROM) expression in normal pituitary tissues and tumor tissues of patients with prolactinoma and to examine the impact of the P450AROM expression on clinical outcome. Twenty-six consecutive human pituitary tissue samples were obtained from autopsies performed at the Institute of Forensic Medicine. Sixty-four patients who had an adenomectomy between 2000 and 2009 after prolactinoma diagnosis with histologically confirmed pituitary tumor tissues were retrospectively included in this study. The slices from the pituitary tissues were subjected to immunohistochemical staining for evaluation of P450AROM and estrogen receptor beta (ER beta) subunit. Immunohistochemistry results were compared according to age, gender, remission rate, resistance and invasion status of the patients. Higher than normal P450AROM expression was found in the pituitary tissues of the patients with prolactinoma (p < 0.001). P450AROM intensity had no relation to resistance or remission in patients with prolactinoma (p = 0.44, p = 0.45, respectively). The subgroup analysis showed that compared to males without invasive adenoma, males with invasive adenoma had higher P450AROM expression (p = 0.048). ER beta was found to have an impact on resistance (p = 0.049). This study shows that P450AROM expression is present in the pituitary tissues of patients with prolactinoma and that this presence could be important in development and tumor behavior of prolactinomas.     

Xanthelasmas of the upper gastrointestinal tract

Background Gastric xanthelasma is a benign and uncommon lesion with a variably reported frequency, while esophageal and duodenal xanthelasmas are quite rare.Methods Seventeen patients who had the diagnosis of xanthelasma in the upper gastrointestinal tract were analyzed retrospectively with respect to their demographic, clinical, endoscopic, and histopathologic features. All lesions suspected as xanthelasma were totally removed by either hot biopsy forceps or a snare with the technique of endoscopic mucosal resection.Results The incidence of upper gastrointestinal xanthelasmas in 7320 patients who had upper gastro-intestinal endoscopy was 0.23%. There were 9 (53%) men and 8 (47%) women, with a median age of 50 years (range, 24–80 years). The most common location of xanthelasmas was the stomach (76%), followed by the esophagus (12%) and duodenum (12%). All lesions were observed as yellow-white colored plaques at endoscopy. Multiple xanthelasmas were detected in 4 patients (24%); in the duodenum in 2, esophagus in 1, and stomach in 1. One patient had xanthelasma within a gastric hyperplastic polyp. The size of the lesion was less than 5mm in diameter in 14 (82%) patients and between 5 and 10mm in diameter in 3 (18%). Thirteen (76%) patients had moderate to severe atrophic gastritis, while the remainder had normal gastric mucosa.Conclusions Xanthelasmas of the upper gastrointestinal tract were mostly located in the stomach in the present series, which includes the second and third reported cases of duodenal xanthelasma, the second case of xanthelasma developed within a hyperplastic gastric polyp, and the fourth and the fifth cases of esophageal xanthelasma.     

Preliminary study showing the relationship between platelet fibronectin, sialic acid, and ADP-induced aggregation levels in coronary heart disease.

Several studies indicate that thrombosis plays an important role in the pathogenesis of coronary heart disease (CHD). Fibronectin is a multifunctional protein in plasma, other body fluids, and cell surface and plays an important role in platelet functions, including mediation of cell-cell and cell-surface interactions. Sialic acid is a regular constituent of glycoproteins and gangliozides in the outer cell membrane of mammalian cells. Therefore, the sialic acid content of platelets, which are characterized by their ability to aggregate with each other, can be important in leading to thrombus formation. In this study, platelet fibronectin, sialic acid-, and adenosine diphosphate (ADP)-induced platelet aggregation levels were determined in patients with CHD. Platelet sialic acid concentrations were determined by Warren's method. Platelet aggregation tests with ADP in platelet-rich plasma (PRP) were analyzed by use of an aggregometer. Platelet homogenate fibronectin levels were determined by ELISA. Total protein levels were determined by Lowry method. Our results indicate that, in patients with no vessel disease (patients with no obstructed vessel but suffering from chest pain, like angina pectoris) platelet fibronectin levels were significantly lower than the total of the other patients (patients with 1, 2, or 3 obstructed coronary vessels) (p<0.05). Sialic acid levels in patients with no vessel disease were significantly lower than the total of the patient group (p<0.05). There was significant (+) correlation between platelet aggregation, platelet fibronectin, platelet sialic acid, and severity of disease (p<0.05). Our preliminary findings suggest that, especially platelet fibronectin levels potentially represent a pathogenic factor for CHD.     

Wide QRS Complex and Lateral ST-T Segment Abnormality Are Associated With Worse Clinical Outcomes in COVID-19 Patients

BackgroundThe information on electrocardiographic features of patients with coronavirus disease 2019 (COVID-19) is limited. Our aim was to determine if baseline electrocardiographic features of hospitalized COVID-19 patients are associated with markers of myocardial injury and clinical outcomes.MethodsIn this retrospective, single center cohort study, we included 223 hospitalized patients with laboratory-confirmed COVID-19. Clinical, electrocardiographic and laboratory data were collected and analyzed. Primary composite endpoint of mortality, need for invasive mechanical ventilation, or admission to the intensive care unit was assessed.ResultsForty patients (17.9%) reached the primary composite endpoint. Patients with the primary composite endpoint were more likely to have wide QRS complex (>120 ms) and lateral ST-T segment abnormality. The multivariable Cox regression showed increasing odds of the primary composite endpoint associated with acute respiratory distress syndrome (odds ratio 7.76, 95% CI 2.67–22.59; p < 0.001), acute cardiac injury (odds ratio 3.14, 95% CI 1.26–7.99; p = 0.016), high flow oxygen therapy (odds ratio 2.43, 95% CI 1.05–5.62; p = 0.037) and QRS duration longer than >120 ms (odds ratio 3.62, 95% CI 1.39–9.380; p = 0.008) Patients with a wide QRS complex (>120 ms) had significantly higher median level of troponin T and pro-BNP than those without it. Patients with abnormality of lateral ST-T segment had significantly higher median level of troponin T and pro-BNP than patients without.ConclusionsThe presence of QRS duration longer than 120 ms and lateral ST-T segment abnormality were associated with worse clinical outcomes and higher levels of myocardial injury biomarkers.