Myocardial ischemia during everyday life in patients with arterial hypertension: prevalence, risk factors, triggering mechanism and circadian variability

INTRODUCTION: The objective of the present study was to investigate the prevalence, the risk factors, the hemodynamic triggering mechanisms, the circadian variability of ST segment depression (ST depression) and the effect of day and night fall in blood pressure on the prevalence of ST depression in hypertensive patients. MATERIALS AND METHODS: In a multicentric study in Germany, 1,244 CardioTens registrations (combined 24-h ambulatory blood pressure measurement/electrocardiography with ST segment triggering; Meditech, Budapest, Hungary) from patients with arterial hypertension were consecutively monitored and evaluated centrally at the University of Bonn. Inclusion criterion was treated or untreated arterial hypertension. The ST segment was measured in accordance with the "1 : 1 : 1 rule" (horizontal or descending ST depression by 1 mm, 1 min duration, 1 min interval from the previous episode). RESULTS: ST segment depression was observed in 250 (20.1%) patients; 90.3% of the transient ST-segment depression was silent (without angina pectoris). Ambulatory 24-h blood pressure measurement, but not office-based blood pressure measurement, was predictive for the occurrence of ST-segment depression. Risk factors for ST-segment depression were the Sokolow index > or =3.5 mV, smoking status, severity of coronary heart disease, use of diuretics, reduced left ventricular function, pulse pressure > or =60 mmHg and increase of double product (1,000 mmHg/min). A significant rise of the systolic/diastolic blood pressure (+8+ or -18/+7+ or -10 mmHg), of the heart rate (+12+ or -13/min) and of the double product (+2,471+ or -2,517 mmHg/min) was found during the transient ST depression as compared with the corresponding 24-h ambulatory blood pressure measurement mean values (P<0.0001 for all parameters specified). In most intermittent ST depressions, a rise of the double product was seen (n=789 episodes), and in the remaining 239 ST depressions, a fall of the double product was observed. ST depressions with fall of the double product showed a circadian distribution with a peak in the late evening. ST depression accompanied by a rise in double product showed two peaks (one in the early morning and one in the late evening). The prevalence of ST depression was significantly higher (28.6%) in extreme dippers than in dippers (18.2%), risers (21.8%) and non-dippers (19.6%). CONCLUSIONS: ST depressions have a high prevalence of 20.1% in hypertensive patients. Clinical predictors for the occurrence of ST-segment depression were classical risk factors and cardiac target organ damage. Office-based blood pressure measurement was not a useful measuring tool for forecasting the likelihood of ST-segment depression. ST depressions were triggered inter alia by variations of blood pressure and the heart rate. The circadian variability of the ST depressions is crucially affected by the pressure double product characteristics on which the ST depression is based.     

Changing Approaches to Cholecystectomy in Elderly Patients: A 10-Year Retrospective Study in Taiwan

Background  

The prevalence of symptomatic gallbladder diseases increases with age. The present study evaluated cholecystectomy risk factors and hospital resource utilization in an elderly (aged 60 years and older) population of patients who had undergone open cholecystectomy (OC) or laparoscopic cholecystectomy (LC).     

Overexpression of protein kinase Calpha mRNA may be an independent prognostic marker for gastric carcinoma

BACKGROUND AND OBJECTIVES: The variability of the prognosis of gastric carcinoma drives extensive researches for novel prognostic markers. The aims of this study were to correlate the expression of protein kinase Calpha (PKCalpha) mRNA with clinicopathological parameters and to evaluate the significant value of PKCalpha in gastric carcinoma prognosis. METHODS: PKCalpha mRNA levels were analyzed in tumor/non-tumor pairs of gastric tissues from surgical specimens of 41 patients with gastric carcinoma employing quantitative real-time polymerase chain reaction. Expression of PKCalpha in gastric carcinoma was also examined using immunohistochemistry. RESULTS: PKCalpha mRNA expression was significantly upregulated in gastric carcinoma (P = 0.007). Overexpression of PKCalpha mRNA was correlated with distant metastasis (P = 0.040). Patients with high PKCalpha mRNA expression had a significantly poorer overall survival compared with patients with low PKCalpha mRNA expression (P = 0.0113). The uni-variate Cox regression analysis showed that high PKCalpha mRNA expression (P = 0.0363) and depth of invasion (P = 0.0443) were two significant prognostic markers for gastric carcinoma. In backward stepwise multi-variate analysis, PKCalpha mRNA overexpression was also proved to be an independent prognostic marker for gastric carcinoma (P = 0.0275). CONCLUSIONS: Our results suggest that overexpression of PKCalpha mRNA has correlation with distant metastasis and may be an independent prognostic marker for gastric carcinoma.     

Comparative laparoscopic evaluation of the PROLENE Polypropylene Hernia System vs. the PerFix Plug repair in a porcine groin hernia repair model

BACKGROUND: Both the PROLENE Polypropylene Hernia System (Ethicon, Johnson & Johnson, Cincinnati, OH) and plug-and-patch devices including the Bard PerFix Plug repair (C.R. Bard. Inc., Murray Hill, NJ) are currently used in open groin herniorrhaphy. These systems rely on incorporating two mesh prostheses of different designs. In this animal study, early results for the two types of device were compared laparoscopically. MATERIALS AND METHODS: Twenty-four uncastrated male pigs (average weight, 25 kg) were randomized into two groups of 12 each for repair of unilateral groin hernia defects with the PROLENE Hernia System (Prolene) or the PerFix Plug (PerFix). Laparoscopic examination was performed immediately after the surgery to check the configuration and coverage area of the preperitoneally positioned mesh devices, with stress-loading tests to compare their primary efficiency. RESULTS: By contrast to the PerFix prostheses, in which the preperitoneal cone-shaped mesh only obliterated the primary fascial defect, in two-thirds of the Prolene repairs the flat and widely deployed underlay patch not only overlapped the defect but also covered the entire myopectineal orifice. Under heavy stress loading (25 newtons), the Prolene group also had a significantly lower incidence of fascial defect exposure in comparison to the PerFix counterparts (P = 0.003). In the stress-loading tests, four Prolene and eight PerFix plugs failed (P >0.005), mainly due to tissue disruption. CONCLUSION: Properly implanted Prolene devices have a wider coverage area and lower risk of fascial defect exposure and thus should be the treatment of choice for large groin hernia defects where the inguinal floor is attenuated. Where the PerFix devices are used under these conditions, they must be adequately secured to a healthy fascial edge, with onlay coverage patches to eliminate any weak points that might cause early recurrence.     

Combretastatin A4-induced differential cytotoxicity and reduced metastatic ability by inhibition of AKT function in human gastric cancer cells

Combretastatin A4 (CA4) is a drug that targets tumor vasculature to inhibit angiogenesis. Whether CA4 has a direct effect on gastric cancer is not known. We herein investigated the effect of CA4 on growth and metastasis of gastric cancer cells at clinically achievable concentration and explored the associated antitumor mechanisms. Nine human gastric cancer cell lines, including two metastatic gastric cancer cell lines (AGS-GFPM1/2), constitutively expressing green fluorescence protein (GFP) were used. These metastatic AGS-GFPM1/2 cells expressed a higher level of phosphorylated serine 473 on AKT (p-AKT). Our results showed that CA4 (0.02-20 microM) has significant in vitro effects on reducing cell attachment, migration, invasiveness, as well as cell cycle G2/M disturbance on p-AKT-positive gastric cancer cells. In addition, a phosphoinositide 3-kinase inhibitor, LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride], a specific AKT inhibitor, and 0.2 to 20 microM CA4 displayed a similar response profile on p-AKT-positive cells, suggesting that CA4-induced effect was mediated by inhibition of the PI3 kinase/AKT pathway. The results from in vivo GFP monitoring system indicated that CA4 phosphate (CA4-P; 200 mg/kg) significantly inhibited the s.c. and intra-abdominal growth of xenotransplanted AGS-GFPM2 cells in nude mice. Furthermore, CA4-P treatment showed a remarkable ability to inhibit gastric tumor metastasis as well as attenuate p-AKT expression. In conclusion, our study is the first to find that CA4 inhibited AKT activity in human gastric cancer cells. The decreased AKT activity correlated well with the CA4 antitumor growth response and decrease of metastasis. Further investigation on drugs targeting the PI3 kinase-AKT pathway may provide a new approach for the treatment of human gastric cancer.     

Deregulated expression of sprouty2 and microRNA-21 in human colon cancer: Correlation with the clinical stage of the disease

Sprouty protein is a novel feedback regulator involved in downstream inactivation of several growth factor receptor pathways. Sprouty2 (Spry2) protein was shown to be downregulated in human cancers. High levels of microRNA-21 (miRNA-21) expression have been associated with poor survival and poor response to adjuvant chemotherapy in cancer patients. But the effect of Spry2 in human colon cancer remained unknown. Paired tumor and normal mucosa samples from patients were examined for their expression of Spry2 mRNA and miRNA-21 by real-time quantitative RT-PCR analysis. Our results show that Spry2 was downregulated in human colon cancer, and its expression levels were lower in advanced-stage tumors than in early-stage tumors. There was a negative correlation between the expression levels of Spry2 and miRNA-21. Furthermore, overexpression of Spry2 suppressed the growth and migration of colon cancer cells with a concomitant increase in PTEN expression and reduction of Akt and MAPK phosphorylation. Spry2 inhibited the growth and tumorigenesis of colon cancer cells in vivo. Conclusively, we show for the first time that Spry2 expression is downregulated and miRNA-21 is upregulated in the clinical samples of colon cancer, which correlates with clinical stage of disease. Thus, Spry2 functions as a tumor suppressor in colon cancer.