Management von Patienten mit Aortenklappenstenosen

The slow progression of valvular aortic stenosis enables the left ventricular myocardium to adapt itself to the increasing afterload. When myocardial adaption is exhausted, surgical intervention is urgent, the prognosis, however, is already limited. To quantify the hemodynamic severity of aortic stenosis, transaortic pressure gradients (dp) measured by Doppler echocardiography or hemodynamically are inappropriate, because dp is significantly dependent on the transaortic flow volume. In severe aortic stenosis, despite constant narrowing of the aortic valve aerea, the reduced stroke volume results in decreasing transaortic pressure gradients. With aortic valve resistance or transaortic pressure loss (PL) — the quotient of pressure gradient and stroke volume — the hemodynamic severity of aortic stenosis can be described accurately. If PL is known, a decompensated aortic stenosis (PL > 1 mm Hg/ml) may be differentiated from myocardial failure of another etiology and a concomitant left ventricular outflow tract obstruction. With respect to medical therapy, the prevention of bacterial endocarditis and thromboembolic complications is important. Knowing the potential danger of syncopies and ventricular arrhythmias during exercise with increasing severity of aortic stenosis, patients have to be informed about their limited functional capacity. The occurrence of typical symptoms during the natural history of chronic aortic stenosis (e. g. dizziness, syncopes, angina pectoris, arrhythmias) manifestation of ST-T-alterations or silent myocardial ischemias and demonstration of an inadequat myocardial adaption to the chronic pressure overload in asymptomatic patients are accepted indications for a surgical intervention. If the indication for surgery remains uncertain, stress tests (e. g. radionuclidventriculography) may be performed to demonstrate an exhausted myocardial adaption. If the PL and the severity of aortic valve/anulus calcification is known, the progression of a chronic aortic stenosis can be estimated. This might be important, if a cardiosurgical intervention has to be performed for other indications and aortic stenosis is co-existent but does not require an intervention at that time. For prognostic reasons myocardial decompensation due to aortic stenosis is an indication for an urgent surgical intervention. Attempts for medical recompensation or bridging strategies (e. g. ballon valvotomie) worsens the prognosis significantly.     

Increased amount of a mitochondria-associated 21 x 103 dalton protein in human gastrointestinal tumors

Summary Differences in the structure and number of mitochondria in tumor cells were found. Using isoelectrofocussing two-dimensional polyacrylamide gel electrophoresis which allows detection of alterations in the protein pattern of tumor mitochondria, we studied both quantitative and qualitative changes in the mitochondrial protein pattern of human gastrointestinal tumors and corresponding normal matrix tissues. One low molecular protein spot was found to be quantitatively changed in the tumors. The approximate molecular weight was 21 x 103 daltons and the pl value 5.7.Dedicated to Dr. Hellmuth Sitte on the occasion of his 60th birthday     

Reliability of Pudendal Nerve Terminal Motor Latency

Abstract Background: The aim of this study was to investigate the inter- and intraindividual variability of the pudendal nerve terminal motor latency (PNTML) in healthy volunteers to evaluate the reproducibility of this method. Probands and Methods: Eleven young healthy probands underwent measurements of PNTML on 2 different days within an interval of 2 months three times a day (morning, noon, evening) under absolute standardized conditions. The examinations were performed by one investigator. Results: Values of 2.1 ± 0.3 ms were measured for the right pudendal nerve and of 2.0 ± 0.3 ms for the left side. Low inter- and intraindividual variability was found with median changes between 7.4% and 16.7% and between 0% and 12.5%, respectively. Morning values were reproducible on the right as well as on the left side, whereas noon and evening values differed significantly. Conclusion: To get reproducible results we conclude that the measurement of PNTML should be performed in the morning     

Effects of various recombinant human hemopoietic growth factors (rhEpo,rhG-CSF,rhGM-CSF,rhIl-3) on the growth of peripheral blood progenitor cells (BFU-E,CFU-GM)

Summary The effects of rhEpo 1, rhG-CSF, rhGM-CSF and rhIl-3 on the growth of both CFU-GM and BFU-E from normal human adult peripheral blood have been studied in plasma clot cultures. Using optimal concentrations of all growth factors, alone and in combination with all other factors, rhIl-3 showed the highest activity in regard to growth of both CFU-GM and BFU-E, whereas rhGM-CSF treatment resulted only in half-maximal colony growth compared to rhIl-3. No synergism or additive effect was seen with the combination of rhIl-3 and rhGM-CSF. Treatment with rh-G-CSF had no additional effect with optimal concentrations of rhIl-3 and/or rhGM-CSF. When suboptimal concentrations of rhGM-CSF and rhIl-3 were applied, however, they showed a marked synergism on both BFU-E and CFU-GM. RhGCSF, added to a suboptimal concentration of rhGM-CSF, resulted in a marked growth increase of CFU-GM but had no effect on BFU-E.Abbreviations BFU-E Burst forming unit-erythroid - CFU-GEM Colony forming unit-granulocytic/erythroid/monocytic/megacaryocytic - CFU-GM Colony forming unit-granulocytic/monocytic - rhEpo Recombinant human erythropoietin - rhG-CSF Recombinant human granulocyte-colony stimulating factor - rhGM-CSF Recombinant human granulocyte/monocyte-colony stimulating factor - RhIl-3 Recombinant human Il-3     

Specific targeting of hepatitis C virus core protein by an intracellular single-chain antibody of human origin

The hepatitis C virus (HCV) core protein is essential for viral genome encapsidation and plays an important role in steatosis, immune evasion, and hepatocellular carcinoma. It may thus represent a promising therapeutic target to interfere with the HCV life-cycle and related pathogenesis. In this study, we used phage display to generate single-chain variable domain antibody fragments (scFv) to the core protein from bone marrow plasma cells of patients with chronic hepatitis C. An antibody with high-affinity binding (scFv42C) was thus identified, and the binding site was mapped to the PLXG motif (residues 84-87) of the core protein conserved among different genotypes. Whereas scFv42C displayed diffuse cytoplasmic fluorescence when expressed alone in the Huh7 human hepatoma cell line, cotransfection with the core gene shifted its subcellular distribution into that of core protein. The intracellular association of scFv42C with its target core protein was independently demonstrated by the fluorescence resonance energy transfer technique. Interestingly, expression of the single-chain antibody reduced core protein levels intracellularly, particularly in the context of full HCV replication. Moreover, cell proliferation as induced by the core protein could be reversed by scFv4C coexpression. Therefore, scFv42C may represent a novel anti-HCV agent, which acts by sequestering core protein and attenuating core protein-mediated pathogenesis.     

Effects of anti-ischaemic drug therapy in silent myocardial ischaemia type I: the Swiss Interventional Study on Silent Ischaemia type I (SWISSI I): a randomized, controlled pilot study.

AIMS: To determine the effect of anti-ischaemic drug therapy on long-term outcomes of asymptomatic patients without coronary artery disease (CAD) history but silent exercise ST-depression. METHODS AND RESULTS: In a randomized multicentre trial, 263 of 522 asymptomatic subjects without CAD but at least one CAD risk factor in whom silent ischaemia by exercise ECG was confirmed by stress imaging were asked to participate. The 54 (21%) consenting patients were randomized to anti-anginal drug therapy in addition to risk factor control (MED, n = 26) or risk factor control-only (RFC, n = 28). They were followed yearly for 11.2 +/- 2.2 years. During 483 patient-years, cardiac death, non-fatal myocardial infarction, or acute coronary syndrome requiring hospitalization or revascularization occurred in 3 (12%) of MED vs. 17 (61%) of RFC patients (P < 0.001). In addition, MED patients had consistently lower rates of exercise-induced ischaemia during follow-up, and left ventricular ejection fraction remained unchanged (-0.7%, P = 0.597) in contrast to RFC patients in whom it decreased over time (-6.0%, P = 0.006). CONCLUSION: Anti-ischaemic drug therapy and aspirin seem to reduce cardiac events in subjects with asymptomatic ischaemia type I. In such patients, exercise-induced ST-segment depression should be verified by stress imaging; if silent ischaemia is documented, anti-ischaemic drug therapy and aspirin should be considered.     

Optimal Frequency of Patient Monitoring and Intensity of Oral Anticoagulation Therapy in Valvular Heart Disease

Age-adjusted mortality due to cardiovascular disease (CVD) has declined by more than 50% over the past three decades; however, CVD continues to be the leading cause of death in the United States. In 1994, 1.25 million people experienced an acute myocardial infarction (AMI). Nearly 500,000 Americans died from CVD, and more than half of these deaths occurred suddenly, within 1 hour of symptom onset, outside the hospital setting. The National Heart Attack Alert Program (NHAAP) endorses the view of the American Heart Association that the community should be recognized as the ultimate coronary care unit. Rapid identification and early treatment are supported by research that demonstrates time is a fundamental factor in reducing morbidity and mortality from AMI and cardiac arrest. A dramatic relationship has been shown between the onset of AMI symptoms, reperfusion treatment, and outcome for patients treated within the first hour after the onset of symptoms. The golden hour has become a widely recognized term in the trauma field, and communities and states are encouraged to develop and implement regional and statewide plans to ensure that trauma patients receive appropriate care within 1 hour of injury. The primary premise of this report — that planning by communities for rapid recognition and triage of patients with symptoms and signs of acute coronary syndromes will result in better outcomes for patients with AMI, including sudden cardiac arrest — is largely based on experience with trauma patients, a population that is benefitting from similar community planning efforts. This NHAAP report reviews community planning considerations and the essential components of an effective community plan (i.e., action plans and protocols, equipment and resources, education and training, and continuous quality improvement evaluation and research) and provides recommendations for each component. The report also presents strategies to guide communities in developing community cardiac emergency action plans.     

Long-term outcomes of mandibular kinematics following class II malocclusion therapy with removable functional appliance therapy

Objective: To evaluate mandibular kinematics in class I adults following class II therapy with removable functional appliances (RFAs) during the growth period in comparison with orthodontically untreated class I and II individuals.

Methods: Condylar (CRoM) and incisal range of motion (InRoM), velocity during opening and closing, and the mandibular rotation angle were recorded using an ultrasound-based jaw-tracking system in 36 test patients (mean age = 28.03 ± 6.58 years).

Results: Significant group effects were found for CRoM towards the posterior in the right joint (p = 0.002) and InRoM towards the anterior (p = 0.043). The post hoc Tukey test indicates a significantly longer CRoM (posterior) for the right condyle in class II (p = 0.003) and RFA individuals (p = 0.023).

Discussion: The kinematic data imply greater dentoalveolar effects due to RFA therapy than adaptive remodeling of the temporomandibular joint. The class I relationship in the RFA group following treatment indicates stable long-term outcomes.     

Endoscopic Doppler ultrasound after injection therapy for peptic ulcer hemorrhage

BACKGROUND/AIMS: A positive Doppler signal in endoscopic Doppler ultrasound at index endoscopy predicts a high risk for rebleeding from peptic ulcer. The aim of this study was to evaluate if a negative Doppler status immediately after injection therapy may exclude a rebleeding from peptic ulcer in a high-risk cohort. METHODOLOGY: Twenty consecutive patients (pts) (age: 68 (33-91) yrs; 11 female) with peptic ulcer bleeding were enrolled. All patients with an actively bleeding ulcer and those with a non-actively bleeding, but Doppler-positive ulcer were treated by injection of adrenaline (1:10,000 dilution). Treatment was performed during index endoscopy until the Doppler status was negative. Patients were followed-up clinically and endoscopically (including Doppler ultrasound) for bleeding recurrence. RESULTS: Patients were treated by injection of 12 (6 to 20) mL of adrenaline solution until Doppler scan was negative. During follow-up four pts (20%) had a clinically overt rebleeding episode. At control endoscopy three ulcers were actively bleeding and another two were Doppler positive without rebleeding (total: five of eighteen (27.7%) Doppler-positive ulcers). Two of the twenty pts required surgical therapy due to rebleeding (10%). CONCLUSIONS: A negative endoscopic Doppler status immediately after injection therapy is not helpful to identify patients with no risk for rebleeding from peptic ulcer.