Phospholipase A2 group IIA expression in gastric adenocarcinoma is associated with prolonged survival and less frequent metastasis

We analyzed gene expression patterns in human gastric cancers by using cDNA microarrays representing approximately equal 30,300 genes. Expression of PLA2G2A, a gene previously implicated as a modifier of the Apc(Min/+) (multiple intestinal neoplasia 1) mutant phenotype in the mouse, was significantly correlated with patient survival. We confirmed this observation in an independent set of patient samples by using quantitative RT-PCR. Beyond its potential diagnostic and prognostic significance, this result suggests the intriguing possibility that the activity of PLA2G2A may suppress progression or metastasis of human gastric cancer.     

Behavioral Similarities and Differences among Alcohol-Preferring and -Nonpreferring Rats: Confirmation by Factor Analysis and Extension to Additional Groups

Thirteen behavioral variables from six tasks were measured in alcohol-preferring (AA, FH, and P) and -non-preferring (ANA, FRL, and NP) rat lines/strains and subjected to Factor Analysis. Four independent factors accounted for >90% of the variance. Defecation in the open field and ultrasonic vocalizations after an air puff were negatively correlated with alcohol intake and preference, whereas the increase in daily fluid intake in the presence of saccharin was positively correlated. Other factors could be labeled Activity, Emotionality, and Immobility Factors, and each was independent of the Alcohol Factor. When an additional alcohol-preferring rat line (HAD) and two additional non-preferring groups (LAD and ACI) were tested, they were found to differ on most behaviors that were associated with alcohol intake and preference in the Factor Analysis: vocalizations and saccharin-induced increase in fluid intake, but not defecation. A new Factor Analysis was then performed incorporating these three new groups and including five new behavioral measures. The following measures had high loadings on the Alcohol Factor: alcohol intake under choice conditions; alcohol preference; forced alcohol intake; alcohol acceptance (forced alcohol intake/basal water intake × 100); ultrasonic vocalization; saccharin intake; saccharin-induced increase in daily fluid intake; defecation in the open field test; and immobility in a modified forced swim test. These findings indicate that there are indeed certain behavioral characteristics that are common among alcohol-preferring rat lines/strains, but there are also substantial group differences on other behavioral measures. For those behavioral measures reflecting emotionality (defecation and ultrasonic vocalization) that loaded highly on the Alcohol Factor, the alcohol-preferring rats had lower scores.     

Persistence of Chlamydia pneumoniae in degenerative aortic valve stenosis indicated by heat shock protein 60 homologues

BACKGROUND AND AIMS OF THE STUDY: Based on the concept of chronic persistent infections with Chlamydia pneumoniae among variable stressors for aortic valve degeneration, the study aim was to assess the presence of chlamydial heat shock protein (cHSP) 60 and its human homologue (hHSP60) in diseased valvular tissue. METHODS: Surgical specimens of high-grade stenosed, native (n = 33) and bioprosthetic (n = 10) aortic valves were examined immunohistochemically for the localization of cHSP60, hHSP60 and macrophages (CD68), supplemented by polymerase chain reaction (PCR) and electron microscopy to prove microbial presence. RESULTS: Degenerated valves showed specific immunostaining of cHSP60 in 27 cases (65%), of hHSP60 in 26 (63%), and of CD68 in 36 (84%). Both HSP60 homologues were predominantly detected in valvular fibrosa, consistently co-localized with macrophages and, quantitatively, showed a strong correlation (r = 0.81, p < 0.001). Presence of C. pneumoniae was demonstrated by PCR in a subset of 11 of 18 valves (61%). Microbial persistence was confirmed by ultrastructural analysis. Degenerated prosthetic valves revealed markedly higher macrophage infiltration and cHSP60 signaling compared with degenerated native valves (each p < 0.05). CONCLUSION: Beyond detection of C. pneumoniae, the present data on co-localization and valvular predilection sites (fibrosa) of both HSP60 homologues indicate the presence of chronic persistent C. pneumoniae infection as well as regional stressor effects, and suggest their involvement in native and prosthetic valve degeneration.     

Percutaneous Trans‐Coronary Venous Mitral Annuloplasty in Patients With Functional Mitral Regurgitation: Analysis of Poznan Carillon Registry Data

Objectives

The purpose of our study is to verify, whether percutaneous mitral annuloplasty results in reverse remodeling in patients with functional mitral regurgitation (FMR) and impaired ejection fraction (EF) and to investigate which echo parameters may help in prediction of the efficacy of the procedure.

Background

FMR exacerbates left ventricular (LV) dilatation and contributes to both LV remodeling and heart failure.

Methods

We analyzed baseline and 1 month follow‐up data in 22 consecutive patients with FMR, who underwent successful percutaneous trans‐coronary venous mitral annuloplasty with the Carillon device.

Results

Significant reduction of FMR echo parameters, including vena contracta (VC), effective regurgitant orifice area (EROA), and regurgitant volume (RV) were observed and maintained throughout 1 month follow up and did not correlate with baseline annular, LV or with the left atrial diameters. Baseline mitral tenting area correlated negatively with the relative improvement (% difference) of EROA (r = ?0.5898) and RV (r = ?0.4363), but not with VC (r = 0.1341). In addition, increased EF as well as a significant reduction in left ventricular diameters were noted. The increase in EF negatively correlated with the change in EROA (r = ?0.50058), PISA (r = ?0.5327), and RV (r = ?0.5457). Baseline mitral tenting area significantly correlated with the 1 month change in EF (r = 0.5946) and stroke volume (r = 0.6913).

Conclusions

The improvement of FMR after treatment with the Carillon device is associated with LV reverse remodeling and an increase in systolic performance, that correlates with the reduction in mitral regurgitation, being not dependent on baseline heart diameters. Mitral tenting area seems to be an important parameter in prediction of benefit from percutaneous mitral annuloplasty.

     

The hemodynamic and neurohormonal effects of low doses of tezosentan (an endothelin A/B receptor antagonist) in patients with acute heart failure

BACKGROUND: In previous studies (the RITZ project), tezosentan, an intravenous (i.v.)-balanced dual endothelin (ET-A/B) antagonist, in doses of 50 and 100 mg/h, improved the hemodynamics but not the clinical outcome of patients with acute heart failure (AHF). OBJECTIVE: To evaluate the effect of lower doses of tezosentan in patients with AHF. SUBJECTS AND METHODS: Included were 130 patients hospitalized due to AHF with dyspnea at rest, despite initial treatment, and were in need of hemodynamic monitoring with cardiac index (CI)<2.5 l/min/m(2) and wedge pressure > or = 20 mm Hg. Patients were randomized in a double-blind fashion to receive placebo or tezosentan: 0.2, 1, 5, or 25 mg/h for 24 h. RESULTS: The primary endpoint of the study, CI increase at 6 h of treatment, was significant in the 5 and 25 mg/h groups. Tezosentan induced a dose-dependent increase in CI and a decrease in wedge pressure, peaking after 3 h in the 5 and 25 mg/h groups. In the 1 mg/h group, this effect was smaller during the first 6 h and increased gradually, becoming significant at 24 h and beyond treatment discontinuation. There was no hemodynamic effect in the 0.2 mg/h arm. Type-B natriuretic peptide (BNP) decreased in the 1, 5, and 25 mg/h groups but not on placebo. Endothelin levels were significantly increased by the 5 and 25 mg/h groups but not in the lower (< or = 1 mg/h) tezosentan doses. Urine output decreased on the 25 mg/h dose. There was a trend towards improvement in patients' subjective dyspnea score and worsening heart failure events, mainly in the 1 mg/h group. CONCLUSIONS: In patients admitted with AHF, tezosentan doses of 1-25 mg/h are efficacious in improving the hemodynamics and reducing BNP. Tezosentan doses beyond 1 mg/h increased plasma endothelin levels and reduced urine output, probably limiting their clinical efficacy, as compared to tezosentan 1 mg/h.     

Ductal plate malformation and congenital hepatic fibrosis Clinical and histological findings in four patients.

Congenital hepatic fibrosis belongs to the fibrocystic diseases of the liver and represents ductal plate malformation of interlobular bile ducts, along with a destructive cholangiopathy associated with fibrosis. Four patients with congenital hepatic fibrosis are described. Their median age at presentation was 25 years; none of them had a family history of liver or renal disease. Variceal bleeding was the initial manifestation in three patients. All of them required frequent endoscopic variceal ligation sessions and distal splenorenal shunting was also performed in two, almost obviating the need for further variceal ligation. Variceal bleeding did not recur during follow-up. One of these three patients rarely exhibited acute cholangitis; administration of ursodeoxycholic acid resulted in complete remission. In contrast, the fourth patient showed frequent severe episodes of acute cholangitis but normal cholangiographic findings. He underwent liver transplantation but died 2 months later. Laboratory findings disclosed pancytopenia in all patients whereas hepatic synthetic capacity was well preserved. Renal function was unaffected despite the presence of polycystic kidneys in two patients. In summary, congenital hepatic fibrosis can also be diagnosed in older ages, might have strikingly different manifestations and is associated with prominent portal hypertension necessitating aggressive management in order to prevent variceal bleeding.     

Trends in hospital treatment of ventricular arrhythmias among Medicare beneficiaries, 1985 to 1995

Background Treatment options for patients with ventricular arrhythmias have undergone major changes in the last 2 decades. Trends in use of invasive procedures, clinical outcomes, and expenditures have not been well documented. Methods We used administrative databases of Medicare beneficiaries from 1985 to 1995 to identify patients hospitalized with ventricular arrhythmias. We created a longitudinal patient profile by linking the index admission with all earlier and subsequent admissions and with death records. Results Approximately 85,000 patients aged ≥65 years went to hospitals in the United States with ventricular arrhythmias each year, and about 20,000 lived to admission. From 1987 to 1995, the use of electrophysiology studies and implantable cardioverter defibrillators in patients who were hospitalized grew substantially, from 3% to 22% and from 1% to 13%, respectively. Hospital expenditures rose 8% per year, primarily because of the increased use of invasive procedures. Survival improved, particularly in the medium term, with 1-year survival rates increasing between 1987 and 1994 from 52.9% to 58.3%, or half a percentage point each year. Conclusion Survival of patients who sustain a ventricular arrhythmia is poor, but improving. For patients who are admitted, more intensive treatment has been accompanied by increased hospital expenditures. (Am Heart J 2002;144:413-21.)     

Effects of melatonin on proliferation of cancer cell lines

Papazisis KT, Kouretas D, Geromichalos GD, Sivridis E, Tsekreli OK, Dimitriadis KA, Kortsaris A.H. Effects of melatonin on proliferation of cancer cell lines. J. Pineal Res. 1998; 25:211–218. © Munksgaard, Copenhagen The pineal hormone melatonin has been reported to have in vitro antiproliferative effects on estrogen receptor-positive human breast cancer cell lines at concentrations near to plasma physiological concentrations (1 times 10^-11 to 1 times 10^-9 M). Its growth inhibitory actions have been thought to be linked to the estrogen-receptor system. We tested the cytotoxic effects of melatonin on MCF-7 and T47D human breast cancer cell lines by using the SRB (sulforhodamine-B), XTT-tetrazolium, and bromodeoxyuridine (BrdU) assays in 96-well microtiter plates. After a 3 or 4 day exposure, melatonin did not have any significant effect on breast cancer cell proliferation and survival in doses up to 1 times 10^-4 M. Doses higher than 1 mM exhibited a potent cytotoxic effect, which was not mediated by the estrogen-receptor or by protein tyrosine kinases and was not specific for breast cancer cell lines. Intracellular glutathione levels did not seem to play any role in the sensitivity of breast cancer cells to melatonin, since the addition of L-buthionine-[S,R]-sulfoximine, ethacrynic acid, or exogenous glutathione did not modify our results. We conclude that under our experimental conditions melatonin has no inhibitory effects on human breast cancer cells at low (physiological or supraphysiological) concentrations. The different experimental procedures that were utilized in the present study can partially explain the divergence between our results and the literature.     

Histopathologic signs for the inflammatory role of Chlamydia pneumoniae in the high-grade atherosclerotic coronary artery wall

The aim of the study was to prove the long-lasting and continuously harmful effect of chronic Chlamydia pneumoniae (CPn) infection on vessel walls in patients with diffuse coronary artery disease (CAD). In surgically obtained endarterectomized atherosclerotic plaques grade VI-VIII (Stary classification) from 10 patients with diffuse coronary artery disease and chronic (7) or past (3) CPn infection, signs of inflammatory response of the vessel wall on infectious agents were studied. In all 10 endarterectomized plaque step serial sections, immunologic signs of vessel wall response were present (positive T- and B-lymphocytes, macrophages, and capillarogenesis). In 8 of 10 patients' atherosclerotic plaque, unique features of active vasculitis in the neoarteriolar wall as well as arteriologenesis, were found. Seven of these 8 patients had serologically proven chronic CPn infection, and 1 had past infection. Features of vasculitis as well as arteriologenesis were absent in 2 patients who recovered from CPn infection at the time of surgery. In the endarterectomized segments of 3 randomly chosen patients in this study, the polymerase chain reaction method revealed positive DNA of CPn. Two of these patients had chronic infection, but the third had only a past CPn infection. This study provides evidence that CPn infection has continuous and a long-lasting inflammatory response in the high-grade atherosclerotic coronary artery vessel wall.