Decreased Plasminogen Activator Inhibitor-1 Levels in Coronary Artery Aneurysmatic Patients

BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of arterial aneurysms through increased proteolysis of extracellular matrix proteins. Increased proteolysis due to elevated matrix degrading enzyme activity in the arterial wall may act as a susceptibility factor for the development of coronary aneurysms. Plasmin strongly stimulates pro-MMP enzyme conversion to the active form. Plasmin hyperactivity due to decreased plasminogen activator inhibitor-1 (PAI-1) may cause MMP over activity and coronary aneurysms. The aim of this study was to investigate the association between PAI-1 and presence of coronary aneurysms. METHODS: Twenty-three patients with aneurysmal coronary artery disease and stable angina were enrolled into study (Group 1). Twenty-two patients without coronary aneurysm were selected as a control group (Group 2). PAI-1 was measured in peripheral venous blood. RESULTS: The plasma PAI-1 level was lower in the coronary artery aneurysmatic patients compared to the control group (8.41 +/- 4.28 vs. 13.32 +/- 10.05 ng/ml, p = 0.037). Serum C-reactive protein (CRP) values were not significantly different between groups (3.83 +/- 1.08 vs. 4.01 +/- 1.35 mg/l, p >0.05). CONCLUSION: Increased matrix degrading enzyme activity can cause arterial wall destruction through increased proteolysis of extracellular matrix proteins. Unregulated plasmin hyperactivity due to decreased inhibition by PAI-1 may play an important role in coronary aneurysm formation.     

Risk factors and algorithms to identify hepatitis C, hepatitis B, and HIV among Georgian tuberculosis patients.

OBJECTIVES: To determine prevalence, risk factors, and simple identification algorithms for HIV, hepatitis B, and hepatitis C co-infection; factors that may predispose for anti-tuberculosis therapy-induced hepatotoxicity. METHODS: We recruited 300 individuals at in-patient tuberculosis hospitals in three cities in Georgia, administered a behavioral questionnaire, and tested for antibody to HIV, hepatitis C (HCV), hepatitis B core antigen (anti-HBc), and the hepatitis B surface antigen (HBsAg). RESULTS: Of the individuals tested, 0.7% were HIV positive, 4.3% were HBsAg positive, 8.7% were anti-HBc positive, and 12.0% were HCV positive. In multivariable analysis, a history of blood transfusion, injection drug use, and prison were significant independent risk factors for HCV, while a history of blood transfusion, injection drug use, younger age at sexual debut, and a high number of sex partners were significant risk factors for HBV. Three-questionnaire item algorithms predicted HCV serostatus 74.1% of the time and HBV serostatus 85.2% of the time. CONCLUSIONS: Treatment of tuberculosis patients in resource-limited countries with concurrent epidemics of HCV, HBV, and HIV may be associated with significant hepatotoxicity. Serologic screening of tuberculosis patients for HBV, HCV, and HIV or using behavioral algorithms to identify patients in need of intensive monitoring during anti-tuberculosis therapy may reduce this risk.     

Investigation of flow-mediated dilation response in normal coronary angiographic patients

Normal findings from coronary angiography do not always show normal endothelial functions. An impaired flow-mediated dilation (FMD) can be a useful marker of the presence of endothelial dysfunction. Hypertension, left ventricular hypertrophy, hypercholesterolemia, and vasospastic angina pectoris can negatively affect FMD response. FMD responses of normal subjects and patients with coronary artery pathology were compared in a prospective cross-sectional study. Patients were divided into 3 groups. Group I patients had a positive exercise stress test and angiographically normal coronary arteries. Group II patients had angiographically significant coronary artery stenosis and stable angina pectoris. Group III had normal results from an exercise stress test and no chest pain. It was concluded that flow-mediated dilation response cannot predict coronary angiographic results. Patients with normal findings from coronary angiography may have impaired endothelial functions.     

Effect of tirofiban on C-reactive protein in non-ST-elevation myocardial infarction

Objectives

C-reactive protein (CRP) is a prototypic marker of inflammation. The effect of tirofiban on CRP levels in patients with non-ST-elevation myocardial infarction (NSTEMI) was investigated.

Methods

The present study was prospective and randomized. Patients with NSTEMI received aspirin, clopidogrel, statin, and unfractionated heparin. Patients with NSTEMI were enrolled into either the tirofiban + heparin group (group 1: n = 25) or the heparin group (group 2: n = 32). Levels of CRP were determined at baseline and after 48 and 72 hours. Heparin and tirofiban were discontinued after 48 hours.

Results

Levels CRP of were similar in two groups at baseline; they increased significantly at 48 hours and 72 hours in the control group but not in the tirofiban group. The differences on and after treatment were statistically significant. In group 1, CRP elevation was attenuated after tirofiban infusion compared with group 2.

Conclusions

Products of platelet activation may aid neutrophil accumulation and enhance inflammation. Activated leukocytes and platelets potentate each others' effects. Tirofiban strongly inhibits the platelet aggregation. The decreased platelet aggregation can suppress the inflammatory protein, chemokine, and adhesion molecule expression. After the tirofiban infusion, CRP elevation was atteunated in patients with NSTEMI.     

Polymorphisms of the methylenetetrahydrofolate reductase, vascular endothelial growth factor, endothelial nitric oxide synthase, monocyte chemoattractant protein-1 and apolipoprotein E genes are not associated with carotid intima-media thickness

BACKGROUND:

Single nucleotide polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), monocyte chemoattractant protein-1 (MCP-1) and apolipoprotein E (ApoE) genes appear to be a genetic risk factor for atherosclerosis. Common carotid intima-media thickness (cIMT) provides information on the severity of atherosclerosis.

OBJECTIVE:

To investigate the relationship between cIMT and gene polymorphisms associated with atherosclerosis in Turkish patients with coronary artery disease (CAD).

METHODS:

Sixty-two patients with angiographically diagnosed stable CAD were divided into two groups according to their cIMT values (group 1: n=35, cIMT of 1 mm or greater; group 2: n=27, cIMT of less than 1 mm). MTHFR 677 C/T, VEGF–460 C/T, eNOS 894 G/T, MCP-1–2518 A/G and ApoE (E2, E3 and E4) gene polymorphisms (where A is adenine, C is cytosine, G is guanine and T is thymine) were analyzed by polymerase chain reaction and restriction fragment length polymorphism. Evaluations of cardiovascular risk factors and coronary atherosclerotic lesions were performed in all patients. Serum homocysteine and high-sensitivity C-reactive protein were measured and compared between the two groups.

RESULTS:

Serum high-sensitivity C-reactive protein (P=0.04) and homocysteine (P=0.006) levels were higher in group 1 than in group 2. The ratio of multivessel CAD and previous myocardial infarction was significantly higher in group 1 than in group 2 (P=0.014). In the study population, no significant difference in cIMT was observed according to the polymorphisms studied. Only hyperhomocysteinemia (OR 1.17 [95% CI 1.01 to 1.35], P=0.033) and previous myocardial infarction (OR 3.76 [95% CI 1.10 to 12.81], P=0.034) maintained a significant correlation with cIMT on multiple logistic regression analysis.

CONCLUSION:

cIMT is increased in patients with hyperhomocysteinemia, inflammation and extended CAD. MTHFR 677 C/T, VEGF–460 C/T, eNOS 894 G/T, MCP-1–2518 A/G and ApoE single nucleotide polymorphisms were not associated with increased cIMT.     

Digoxin intoxication: An old enemy in modern era

Objectives Although development of new treatment modalities limited digoxin usage, digoxin intoxication is still an important issue which could be easily overlooked. In this report we analyzed a case series definitively diagnosed as digoxin intoxication in the modern era. Methods We analyzed 71 patients hospitalized with digoxin intoxication confirmed by history, complaints, clinical and electrocardiograph (ECG) findings, and serum digoxin levels > 2.0 ng/mL, during a five year period. The demographic and clinical data, indications for digoxin use, digoxin dosage, concurrent medications, laboratory data, hospital monitoring, and ECG findings were obtained from all patients. Results Thirty-eight of 71 patients (53.5%) had symptoms of heart failure during admission or later. Sixty-four percent of patients were older than 75 years. The percentage of females was 67%. Atrial fibrillation, hypertension and gastrointestinal complaints were more frequent in the females (64% in females, 30% in males, P = 0.007; 81% in female, 52% in males, P = 0.01; 50% in female, 17.3% in males, P = 0.008, respectively). The mortality rate during the hospital course was 7%. Conclusion This report demonstrated the reduced mortality rates in patients with digoxin intoxication over the study period. Gastrointestinal complaints are the most common symptoms in this population.     

HIV-1 genetic diversity and genotypic drug susceptibility in the Republic of Georgia

The genetic diversity and genotypic drug susceptibility of HIV-1 strains circulating in the Republic of Georgia, formerly part of the Soviet Union, were investigated for first time. Forty-eight HIV-positive drug-naive Georgian individuals contributed PBMC DNA between 1998 and 2003. On the basis of phylogenetic analyses of partial pol sequences, the predominant HIV-1 genetic forms were subtype A (70%), followed by subtype B (26%); both genetic forms were carried by injecting drug users and heterosexuals. There was also one subtype C (2%) and one CRF18_cpx (2%). The Georgian subtype A strains clustered with subtype A from Russia, designated A(FSU). Twelve of the subtype A strains (25%) contained the secondary protease inhibitor mutation V77I and 9 also had two other silent mutations. This "V77I haplotype" marks one particular genetic lineage of the epidemic in the former Soviet Union. Two strains (4%) carried antiretroviral (ARV) drug resistance mutations. Nearly full-length genome sequences of five Georgian strains were also completed. Two, 98GEMZ011 (subtype A) and 98GEMZ003 (subtype B), closely resembled the parental strains that recombined to create CRF03_AB. The use of these parental strains in the analysis revealed an additional segment of subtype A in CRF03_AB. Thus, the HIV-1 epidemic in Georgia was composed of a mixture of subtype A(FSU) and subtype B.     

Is ultrasound of the retroperitoneum a valuable staging method in selecting testicular cancer patients for primary retroperitoneal lymph node dissection?

OBJECTIVE: In nonseminomatous testicular cancer patients with normal serum tumor markers and no distant metastasis, postorchiectomy surgery is a valid treatment option if the disease extension into the retroperitoneum is not advanced. We assessed the ability of ultrasound (US) to exclude the presence of bulky retroperitoneal disease. MATERIALS AND METHODS: One hundred and forty testicular cancer patients underwent US and computed tomography (CT) of the retroperitoneum. US results were analyzed using three cutoffs: 5 cm (conventional staging), 3 cm (based on the minimal sonographical dimension of actual bulky disease) and 0 cm ('clean retroperitoneum' or any detectable nodes), and were compared with CT data using the 5-cm cutoff ('gold standard'). RESULTS: The sensitivity, specificity, overall accuracy, positive and negative predictive values of US in detecting of bulky retroperitoneum for the 5-cm cutoff were 83, 96, 93, 88 and 94%, for the 3-cm cutoff 100, 91, 94, 80 and 100%, and for the 0-cm cutoff 100, 66, 74, 49 and 100%, respectively. CONCLUSIONS: In stage I and IIA/B marker-negative nonseminomas if the treatment strategy is surgery, US may facilitate the selection process; the report of a clean retroperitoneum safely excludes the presence of bulky disease and may be an indication for lymphadenectomy, although in case of positive findings a CT should be performed.