Vascular endothelial growth factor in pleural effusions of different origin.

This study aimed to determine the diagnostic relevance of vascular endothelial growth factor (VEGF) in the pleural fluid and serum of patients with pleural effusions of different aetiology. VEGF was quantified in the pleural effusion fluid and serum of 96 patients with malignancies (58 lung cancers (CA) and 38 tumours with secondaries to the lung (TM)), 45 with congestive heart failure (CHF), 28 with tuberculosis (TB), 45 with acute infections (INF), and in the serum of 20 healthy controls. VEGF pleural effusion concentrations were significantly different in the main diagnostic groups. VEGF was higher in effusions of patients with malignancies (CA as well as TM) in comparison with INF, TB or CHF. In serum, however, high VEGF concentrations indicated CA, TM or INF, but not TB or CHF. Despite significant differences of VEGF levels in different patient groups, receiver-operating characteristic analysis revealed insufficient diagnostic value of VEGF for differential diagnosis of pleural effusions. In conclusion, vascular endothelial growth factor serum concentration is highly suggestive of the presence of lung disease in general, except for tuberculosis. In effusion fluid, the presence of vascular endothelial growth factor clearly indicates inflammatory or malignant origin. However, for diagnostic use, additional parameters besides vascular endothelial growth factor are mandatory.     

Budd-Chiari syndrome as the primary manifestation of a fibrolamellar hepatocellular carcinoma.

An 18-year-old female patient was admitted with ascites, right upper abdominal tenderness and peripheral edema. Angiography showed complete occlusion of the vena cava inferior up to the level of the right atrium. By open heart surgery, masses of thrombotic material were pulled out of the v. cava inferior/vv. iliacae which histologically contained tumor cell populations consistent with a hepatocellular carcinoma. Celiacography showed a highly vascularized tumor in the right hepatic lobe. Histologically, it proved to be fibrolamellar subtype hepatocellular carcinoma.     

Impact of carbon coating on the restenosis rate after stenting of atherosclerotic renal artery stenosis.

PURPOSE: To investigate the impact of carbofilm coating and low-profile rapid exchange stent devices on the restenosis rate after stent-angioplasty of atherosclerotic renal artery stenosis (RAS). METHODS: During a 2-year period (7/2002-7/2004), 143 consecutive patients with 179 primary ostial atherosclerotic RAS>or=70% diameter stenosis were treated with stents selected at the discretion of the operator. Eighteen patients (32 lesions) treated with 9 different types of stents were excluded from the analysis, leaving 125 patients (69 men; mean age 67 years, range 42 to 90) with 147 lesions who received either a Radix carbofilm-coated stent in 78 (53%) lesions (68 [54%] patients) or a Palmaz Genesis bare stainless steel stent in 69 (47%) lesions (57 [46%] patients). The target vessel diameter ranged from 5 to 7 mm. RESULTS: Baseline characteristics were similar in both groups except the mean stent diameter, which was larger in the bare stent cohort (6.4+/-0.7 versus 5.9+/-0.5 mm, p<0.001). Primary success was 100% in both groups; the initial mean diameter stenosis was reduced from 79%+/-14% and 80%+/-14% in the coated versus bare stent groups to 3+/-5% and 2+/-6%, respectively. After a mean follow-up of 22+/-5 months, the restenosis rate was 6.4% for the coated stent and 5.8% for the bare stent (p=0.87). For the entire cohort, restenosis rates varied significantly (p<0.05) according to stent diameter: 19% (5/26) for 5 mm, 4% (3/81) for 6 mm, and 2.5% (1/40) for 7 mm. In a binary logistic regression analysis including carbofilm coating, stent diameter, gender, diabetes, smoking status, and body mass index, stent diameter was the only independent predictor of restenosis (odds ratio 0.12, 95% CI 0.03 to 0.48 [p=0.003] for a 1-mm increase in vessel diameter). CONCLUSIONS: Using modern low-profile stent devices, carbofilm coating does not significantly reduce the restenosis rate compared to a bare metal stent. With contemporary stent devices, the restenosis rate has been decreasing compared to earlier reports in the literature.     

Acute meningitis

Recent major epidemiologic trends in bacterial meningitis include a dramatic decline in the incidence of Haemophilus influenzae meningitis since the introduction of the protein-conjugated H. influenzae vaccines, and a worldwide increase in infections with antibiotic-resistant strains of bacterial pathogens. Cases of meningitis caused by resistant strains require an alternative therapeutic strategy. Animal studies have identified inflammatory mediators, eg, chemokines, excitatory amino acids, and endothelins, which are involved in the pathophysiology of bacterial meningitis. There is increasing evidence that reactive oxygen species (ROS), reactive nitrogen species, peroxynitrite, and matrix metalloproteinases contribute to brain damage during bacterial meningitis. The cytotoxic effects of ROS and peroxynitrite include the initiation of lipid peroxidation and the induction of DNA single-strand breakage. Damaged DNA activates poly(ADP-ribose) polymerase (PARP). Recent experimental data suggest that lipid peroxidation and PARP activation play a role in the development of meningitis-associated intracranial complications and brain injury. Agents that interfere with the production of ROS and peroxynitrite, and interfere with lipid peroxidation and PARP activation, may represent novel, therapeutic strategies by which meningitisassociated brain damage can be limited, therefore improving the outcome of this serious disease.     

Clinical utility of intrathoracic impedance monitoring to alert patients with an implanted device of deteriorating chronic heart failure.

AIMS: To evaluate the utility of intrathoracic impedance monitoring for detecting heart failure (HF) deterioration in patients with an implanted cardiac resynchronization/defibrillation device. METHODS AND RESULTS: Patients enrolled in the European InSync Sentry Observational Study were audibly alerted by a device algorithm if a decrease in intrathoracic impedance suggested fluid accumulation. Clinical HF status and device data were assessed at enrolment, during regular follow-up, and if patients presented with an alert or HF deterioration. Data from 373 subjects were analysed. Fifty-three alert events and a total of 53 clinical events (HF deterioration defined by worsening of HF signs and symptoms) were reported during a median of 4.2 months. Adjusted for multiple events per patient, the alert detected clinical HF deterioration with 60% sensitivity (95% CI 46-73) and with a positive predictive value of 60% (95% CI 46-73). Higher NYHA class at baseline was predictive for adequate alert events during follow-up (P < 0.05). In 11 of 20 HF deteriorations without preceding alert, an upstroke of the fluid index occurred without reaching the programmed alert threshold. CONCLUSION: A device-based algorithm that alerts patients in case of decreasing intrathoracic impedance facilitates the detection of HF deterioration. Future randomized, controlled trials are needed to test whether the tailored use of intrathoracic impedance monitoring can improve the ambulatory management of patients with chronic HF and an implanted device.     

Antivirale Therapie bei viraler Herzerkrankung

Several investigations showed that in addition to genetic factors also virological and chronic inflammatory aspects are relevant pathogenic mechanisms for the development of dilated cardiomyopathy (DCM). Based on the etiopathogenic importance of viral persistence and chronic myocardial inflammation for disease progression, novel rational therapeutic strategies have been developed. The diagnosis of chronic myocardial inflammation and viral persistence has been a controversial issue for a long time due to diagnostic pitfalls. Detection of persistence of viral genomes with adequate sensitivity and specificity succeeded only by the establishment of sensitive molecular biological techniques such as in situ hybridization and nested polymerase chain reaction (nPCR). By the use of these molecular biological methods, further viruses have been detected in DCM patients in addition to the classic cardiotropic viruses (entero- and adenoviruses), particularly parvovirus B19, human herpes virus type 6 (HHV-6), and Epstein-Barr virus. Considering these different cardiotropic viruses, viral persistence can be proven in > 50% of the DCM patients, consistent with the diagnosis of viral heart disease.This differentiated diagnosis enables, in addition to symptomatic therapy of heart failure, novel rational therapeutic regimens (e. g., beta-interferon) in the setting of randomized trials such as the BICC Study (Betaferon In Patients with Chronic Viral Cardiomyopathy).     

Patients using statin treatment within 24 h after admission for ST-elevation acute coronary syndromes had lower mortality than non-users: a report from the first Euro Heart Survey on acute coronary syndromes.

AIMS: Statins provide effective secondary prevention in cardiovascular disease. However, it remains uncertain how soon statins should be started after an acute coronary syndrome (ACS). Recently published trials suggest starting before discharge. We hypothesize that statins should be initiated without delay. METHODS AND RESULTS: Data from a large cohort of 10,484 consecutive patients with an ACS were analysed. Of this cohort, 1426 first-time statin receivers and survivors of the first 24 h were compared with 6771 first-day survivors not receiving statin therapy. A propensity score for the likelihood of receiving statin therapy within 24 h was developed and used with other established risk factors in a multivariable analysis. There was a significantly reduced all-cause 7-day mortality in patients receiving early statin therapy [0.4 vs. 2.6%, unadjusted hazard ratio (HR) 0.16, 95% confidence interval (CI) 0.08-0.37, adjusted HR 0.34, 95% CI 0.15-0.79]. Statistical significance was observed in patients presenting with STE-ACS (adjusted HR 0.17, 95% CI 0.04-0.70) and not in NSTE-ACS patients. However, no statistical evidence of heterogeneity in treatment effect was observed between these groups. CONCLUSION: These data suggest that very early statin therapy is associated with reduced mortality in patients presenting with STE-ACS; however, these findings have to be confirmed by prospective, randomized controlled trials before firm treatment recommendations can be given.     

Exhaled breath condensate acidification in acute lung injury

Lung injury in ventilated lungs may occur due to local or systemic disease and is usually caused by or accompanied by inflammatory processes. Recently, acidification of exhaled breath condensate pH (EBC-pH) has been suggested as marker of inflammation in airway disease. We investigated pH, ammonia, Lactate, pCO2, HCO3-, IL-6 and IL-8 in EBC of 35 ventilated patients (AECC-classification: ARDS: 15, ALI: 12, no lung injury: 8). EBC-pH was decreased in ventilated patients compared to volunteers (5.85 +/- 0.32 vs. 7.46 +/- 0.48; P < 0.0001). NH4+, lactate, HCO3-, pCO2, IL-6 and IL-8 were analyzed in EBC and correlated with EBC-pH. We observed correlations of EBC-pH with markers of local (EBC IL-6: r = -0.71, P < 0.0001, EBC IL-8: r = -0.68, P < 0.0001) but not of systemic inflammation (serum IL-6, serum IL-8) and with indices of severity of lung injury (Murray's Lung Injury Severity Score; r = -0.73, P < 0.0001, paO2/FiO2; r = 0.54, P < 0.001). Among factors potentially contributing to pH of EBC, EBC-lactate and EBC-NH4+ were found to correlate with EBC-pH. Inflammation-induced disturbances of regulatory mechanisms, such as glutaminase systems may result in EBC acidification. EBC-pH is suggested to represent a marker of acute lung injury caused by or accompanied by pulmonary inflammation.     

Additive effects of the chemokine receptor 2, vitamin D receptor, interleukin-6 polymorphisms and cardiovascular risk factors on the prevalence of myocardial infarction in patients below 65 years

BACKGROUND: Cardiovascular risk factors (CRF) have been associated with myocardial infarction (MI), while the role of genetic risk factors (GRF) remains undetermined. METHODS: Cineventriculograms of 3436 were analyzed for presence of regional function impairment as sign of MI. Genotyping for genetic polymorphism (vitamin D receptor VDR BsmI, interleukin-6 IL6-174 G/C, chemokine receptor 2 CCR2 64 V/I) was performed. CRF were assessed (hypertension, hypercholesterolemia, smoking, and diabetes mellitus). RESULTS: In patients <65 years (n=1946) genotypes (VDR BB, IL6 GC/CC, CCR2 VI/II, defined as GRF) were significantly associated with the presence of MI (BB: OR 1.38, 95%CI 1.07-1.79, p=0.016 GC/CC: 1.28, 95%CI 1.03-1.60, p=0.028 VI/II: 1.49, 95%CI 1.17-1.88, p=0.001). Combining four CRF (14% vs. 21% vs. 27% vs. 31% vs. 38%, p<0.0001) and three GRF (21% vs. 25% vs. 32% vs. 44%, p<0.0001) revealed additive effects on the prevalence of MI. The more combined CRF and GRF were present (from 0 to 7) the higher was the prevalence of MI (11% vs. 12% vs. 21% vs. 27% vs. 30% vs. 34% vs. 59%, p< 0.0001). Age was not associated with MI. In patients > or =65 years (n=1490) the combination of CRF was only weakly associated with MI, while GRF were not. In these patients age was a predictor of MI. CONCLUSION: Certain GRF might have additive but small effects on the disposition for MI before the age of 65. In older patients the tested GRF had no effect, possibly indicating a mechanism of aging rather than a purely genetic determined entity. Given the small effect of the tested genetic polymorphisms the value of testing GRF remains uncertain.     

sICAM-1 correlates with myocardial ICAM-1 expression in dilated cardiomyopathy

BACKGROUND: Dilated cardiomyopathy (DCM) is etiopathogenically linked to intramyocardial inflammation, which is reflected by ICAM-1 abundance. We investigated whether soluble ICAM-1 (sICAM-1) levels in the sera of DCM patients are associated with intramyocardial ICAM-1 expression. METHODS: Immunohistochemically detected ICAM-1 expression was quantified semiquantitatively in endomyocardial biopsies from DCM patients (n=45; n=17 females; age: 48+/-15 years) and from n=12 donor hearts (controls) by a human observer (baseline vs. enhanced expression) and quantitatively by a digital image analysis (DIA) system. The DIA-measured qualities were area fraction (AF), surface-volume ratio (SVR) and integral optical density (ID). The sICAM-1 levels of the DCM patients and n=12 healthy volunteers (controls) were measured by ELISA (means of duplicate measurements). Intramyocardial ICAM-1 expression and sICAM-1 levels were compared in these DCM patients. RESULTS: Of the DCM patients, n=24 (53%) demonstrated statistically higher sICAM-1 levels compared to controls (>198 ng/ml). By semiquantitative and quantitative DIA evaluation, endothelial ICAM-1 abundance was present in n=25 (56%) of the DCM biopsies. sICAM-1 correlated significantly (P<0.001) both with the semiquantitatively assessed and the DIA-measured ICAM-1-AF, the ICAM-1-SVR and the ICAM-1-ID. The positive predictive value of sICAM-1 measurements for intramyocardial ICAM-1 abundance was 96%, and the negative predictive value was 71%, with a receiver operating characteristic area under the curve of 0.93. Furthermore, sICAM-1 levels correlated with intramyocardial T-lymphocytic (CD2+/CD3+) infiltrates (P<0.03). CONCLUSIONS: Measurement of non-invasively obtained sICAM-1 reliably reflects intramyocardial ICAM-1 expression and may therefore serve as a non-invasive marker of inflammatory activity in DCM.