[Dyspnea in left-sided heart disease]. / Dyspnoe bei Linksherzerkrankungen.

Shortness of breath (dyspnea) is a common symptom in left-sided heart disease but clinically, patient symptoms show a high variability. Echocardiography is the mainstay for evaluating whether left-sided heart disease is the cause of dyspnea. If left-sided heart failure is diagnosed, this symptom complex must then be subjected to further etiological evaluation. Hypertensive, ischemic and valvular heart diseases are common, as well as atrial fibrillation. If the patient does not have angina pectoris, testing for ischemic heart disease should be done non-invasively by coronary computed tomography or testing for regional myocardial ischemia. Coronary revascularization is indicated only when a prognostically relevant ischemia of more than 10 % of the left ventricle is diagnosed. Diuretics are important for the relief of dyspnea but do not improve the prognosis of patients. In patients with reduced left ventricular function, combination therapy with angiotensin-converting enzyme (ACE) inhibitors, beta blockers and aldosterone antagonists improve the symptoms and prognosis. For treatment of heart failure with preserved ejection fraction evidence-based measures are still lacking. In this case the recommended therapy consists of optimal treatment of comorbidities, regulation of heart rate and blood pressure and participation in structured exercise programs. Angiotensin receptor blockers and aldosterone antagonists can be given in patients with more severe symptoms even though the available data are very sparse.

[Vertigo and syncope: a clinically oriented introduction to the problem]. / Schwindel und Synkope: Eine klinisch orientierte Hinführung zum Problem.

Vertigo and syncope are frequently occurring clinical presentations in the physician's practice as well as in the emergency room. Therefore, many physicians and institutions have formulated diagnostic protocols that they follow when a patient with vertigo or syncope presents. This kind of blanket routine may lead to over-diagnosis in many cases, as well as to under-diagnosis in some. The purpose of the following article is to show that a well-focused history based on clear cut concepts of disease and a sound pathophysiological understanding will guide the physician precisely through the diagnostic process in both clinical presentations and will help to avoid manifold diagnostic procedures. Finally, a description of the most frequent pitfalls of the diagnostic work-up is given, along with measures to avoid these.

[Cardiogenic syncope]. / Die kardiogene Synkope.

BACKGROUND: Cardiogenic syncope is a serious clinical event and the cause has to be clarified as rapidly and definitively as possible. DIAGNOSTICS: With knowledge of the pathophysiological background the reason for syncope can mostly be clarified by taking a thorough medical history. In most cases a physical examination, electrocardiogram (ECG) and echocardiography can provide sufficient evidence for most of the causes. Rhythmogenic syncope, however, often tends to be extremely difficult to diagnose which is why many different instruments have been developed for the detection of changes in heart rhythm. Several drugs can induce syncope by different modes of action and is the reason why particular attention should always be paid to this aspect.

[Diseases of the peripheral vestibular system: contribution of ENT medical diagnostics and therapy]. / Erkrankungen des peripher-vestibulären Systems: HNO-ärztliche Diagnostik und Therapie.

The most common types of vertigo caused by diseases of the peripheral vestibular system are benign paroxysmal positional vertigo (BPPV), Meniere's disease and vestibular neuritis. A thorough examination of the medical history and clinical examination are usually sufficient for the differential diagnostics. Treatment includes differentiated repositioning maneuvers, medicinal treatment and physiotherapy.

[Reflex syncope and syncope secondary to orthostatic hypotension]. / Reflexsynkopen und Synkopen bei orthostatischer Hypotonie.

BACKGROUND: Reflex syncope predominantly occurs in younger patients and is the most common type of syncope. Typical contributors to reflex syncope are orthostatic stress, followed by a delayed and inadequate circulatory response consisting of bradycardia (cardioinhibitory type) and hypotension (vasodepressor type). Comparably, syncope may occur after direct activation of the vagus nerve, after emotional distress or pain, and in specific situations, such as coughing and post-micturition. The latter situations are mediated by indirect vagus nerve activation by usually unknown mediators. Syncope mediated by orthostatic hypotension occurs in elderly patients and is mediated by insufficient sympathoadrenergic vasoconstriction, occurring shortly after the onset of the orthostatic situation. DIAGNOSTICS: A thorough examination of the patient history is the mainstay of diagnostics. Specific testing is only required in uncertain and recurrent cases. In addition to standard diagnostics, tilt table testing can be helpful. A negative tilt test is, however, not definitive. Implanted loop recorders are helpful to diagnose the cardioinhibitory component of reflex syncope and are more sensitive than tilt testing. THERAPY: Treatment of both types of syncope consists of avoiding known situations leading to syncope, early reaction to prodromal syndromes, and physical counterpressure manoeuvers. Drug treatment (e.g. alpha-adrenergic agonists and fludrocortisone) are effective only in patients with orthostatic syncope. In selected patients with reflex syncope of a predominantly cardioinhibitory type, pacemaker implantation may be considered in selected patients.

[Percutaneous coronary intervention versus bypass surgery in patients with diabetes and multivessel coronary disease. Coronary revascularization after FREEDOM]. / Perkutane koronare Intervention versus Bypass-Operation bei Patienten mit Diabetes und koronarer Mehrgefäßerkrankung. Koronarrevaskularisation nach FREEDOM.

Is coronary revascularization required in a patient with chronic stable coronary artery disease or can optimized medical therapy (OMT) alone be a sufficient alternative? This question has been controversially discussed for non-diabetics as well as for diabetics since the COURAGE and BARI 2D trials. According to our present knowledge, a patient will benefit from coronary revascularization only when either a non-invasive test method, such as single photon emission computed tomography (SPECT) or positron emission tomography (PET) myocardial scintigraphy, stress echocardiography or stress nuclear magnetic resonance imaging, can detect relevant, objective evidence of ischemia >10% of the left ventricular myocardium or when a pathological fractional flow reserve (FFR) <0.80 can be measured in an invasive procedure for an angiographically detectable coronary stenosis. If similar relevant ischemia can be non-invasively or invasively objectified in a patient with chronic stable multivessel coronary artery disease, the often controversially discussed question arises particularly in diabetics whether a percutaneous coronary intervention (PCI) with implantation of drug-eluting stents or coronary artery bypass surgery should be favored. The FREEDOM study (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease), published in November 2012, was the first prospective randomized study to examine this issue in diabetic patients with multivessel coronary artery disease. Despite a higher rate of stroke in the surgical cohort, after an average follow-up time of 3.8 years a significant prognostic advantage in favor of bypass surgery was detected for a combined primary endpoint of all-cause mortality, nonfatal myocardial infarction and nonfatal stroke. Thus, in the new ESC guidelines on diabetes, pre-diabetes and cardiovascular diseases developed with the EASD of the European Society of Cardiology and published in 2013, coronary bypass surgery has a class I, level of evidence A recommendation for patients with diabetes mellitus, chronic stable multivessel coronary disease and a synergy between PCI with taxus and cardiac surgery (SYNTAX) score >22. The decision for or against a PCI/stent implantation or coronary bypass surgery in a diabetic patient with chronic stable multivessel coronary artery disease should therefore be made with the patient only after a detailed informed consent discussion and comprehensive explanation of both treatment options. In controversial cases, particularly with an equivocal SYNTAX score around 22, relevant comorbidities or anticipated method-specific complications, a one-stage ad hoc intervention during the diagnostic coronary angiography should be rejected in favor of a two-stage procedure with prior discussion of both treatment options in the heart team comprising noninvasive cardiologists, interventional cardiologists and cardiac surgeons.

Combined immunosuppressive therapy including a TNF-alpha blocker induces remission in a difficult to treat patient with Takayasu arteriitis and coronary involvement.

A 40 year old woman presented with symptoms of a systemic inflammatory disease and obstruction of the left subclavian artery. Takayasu arteriitis (TA) was clinically diagnosed and confirmed by MR angiography and FDG-PET scan showing inflammation of the aortic arch and the left subclavian artery. Immunosuppression with glucocorticoids and methotrexate resulted in immediate clinical improvement and normalization of systemic markers of inflammation. Despite that the patient developed chest pain on exertion suggesting coronary involvement, which was confirmed by dobutamine stress echocardiography. After adding the TNF-alpha blocker infliximab coronary symptoms gradually improved and a clinically stable situation could be achieved for more than 6 months. Coronary angiography and aortography showed an occluded main stem of the left coronary artery, an occluded left subclavian artery, and stenoses of the brachiocephalic trunk and the left common carotid artery. Revascularization of the coronary artery and the aortic arch and its branches was performed. The patient returned to work two months after the operation. Immunosuppressive therapy with infliximab and methotrexate is continued, glucocorticoids were stopped after one year of treatment. This case shows that vascular progress in TA patients may occur even when systemic inflammation is controlled, therefore patients have to be carefully observed for new vascular manifestations. TNF-alpha blockers may be an additional treatment option in otherwise difficult to treat TA patients allowing to perform revascularization after a stable disease state has been achieved.

[19-year-old asthma patient with pronounced eosinophilia and acute coronary syndrome]. / 19-jähriger Asthmatiker mit ausgeprägter Eosinophilie und akutem Koronarsyndrom.

Diagnosis of Churg-Strauss syndrome should be considered in young asthmatics with fatigue and eosinophilia. On the base of the etiopathology of a 19-year old man, who was initially admitted because of dyspnoea, fever and acute chest pain, we show that eosinophilia gives an important hint for further diagnostic and is the key trend parameter. Histologically an eosinophilic myocarditis could be shown in the myocardial biopsy. High dose prednisolone induced a clear improvement in symptoms, with decrease of the inflammatory signs and the eosinophilia and a clear improvement of the left ventricular function.

Receptor-independent sensitization of the adenylyl cylase after chronic treatment with cyclosporine A.

Chronic treatment with cyclosporine A (CyA) is often complicated by severe hypertension. If activation of the beta-adrenergic-receptor-linked adenylyl cyclase (AC) system contributes to hypertension is unresolved. Rats were treated with CyA (20 mg kg(-1) day(-1)) for 7 days. beta-adrenergic, muscarinic, and alpha-adrenergic receptors, G-proteins, and the activity of AC were determined in cardiac and pulmonary plasma membranes. The density of cardiac beta-adrenergic receptors, muscarinic receptors, alpha-adrenergic receptors, G(alphas) and, G(alphai) remained unchanged after treatment with CyA. However, CyA increased the responsiveness of AC to different stimulators. The responsiveness of AC was even more pronounced after solubilization and partial purification, suggesting a direct modulation of the enzyme. These data suggest that CyA modulates the activity of the sympathoadrenergic system by a direct, receptor-independent sensitization of AC, suggesting that this pathway contributes to hypertension in patients treated with CyA.

[Thrombembolism in a young woman with previously unrecognized hereditary hemophilia: obtaining a family history is still strongly recommended before starting oral contraceptives]. / Familienanamnese vor Neuverordnung einer oralen Kontrazeption: altmodisch, aber immer noch wertvoll.

ADMISSION FINDINGS: A 18-year-old girl was admitted because of dyspnea and chest pain at rest. Her previous medical history was unremarkable except that oral contraceptives had been newly prescribed a month before admission. There was a family history of thrombosis or bleeding in several first-degree relatives. INVESTIGATIONS: Echocardiography and computed tomography revealed bilateral pulmonary embolism caused by a large right atrial thrombus. Laboratory analysis showed prolonged thrombin time and subnormal levels of fibrinogen. Genetic analysis revealed a previously unreported fibrinogen mutation (hypodysfibrinogenemia Dresden I) in the patient and in her relatives. DIAGNOSIS: These findings indicated that the pulmonary embolism had been caused by a right atrial thrombus in a patient with hypodysfibrinogenemia. Recently initiated intake of oral contraceptives had led to manifestation of the disease. TREATMENT: Anticoagulation with heparin followed by coumarin achieved complete resolution of symptoms. CONCLUSION: The atypical course of thromboembolism in this young woman was caused by an underlying hereditary thrombophilia and manifested itself by the prothrombotic effect of newly taken oral contraceptives. If a detailed family history had been obtained before prescribing these drugs thrombotic or bleeding events in the patient's family would have been revealed and could have prevented thromboembolism. This case illustrates the importance of current guidelines according to which a family history should be obtained before starting oral contraceptives.

Transcatheter closure of atrial septal defects improves right ventricular volume, mass, function, pulmonary pressure, and functional class: a magnetic resonance imaging study.

OBJECTIVE: To characterise prospectively by magnetic resonance imaging (MRI) changes in right ventricular (RV) volume, function, and mass after transcatheter closure of atrial septal defects (ASDs) and to evaluate the course of pulmonary pressure and functional class criteria. METHODS: In 20 patients with secundum-type ASD and dilated RV diameter, MRI was performed to quantify RV end diastolic (RVEDV) and end systolic volumes (RVESV), RV mass, tricuspid annular diameter, and RV ejection fraction before and 6 and 12 months after transcatheter closure of the ASD. RV systolic pressure was measured during follow up by transthoracic echocardiography. RESULTS: Functional class improved in the majority of patients after ASD closure. RVESV (from 81 (18) ml/m2 to 53 (15) ml/m2, p < 0.001), RVEDV (from 127 (17) ml/m2 to 99 (18) ml/m2, p < 0.001), and RV mass (from 79 (10) g to 63 (8) g, p < 0.01) decreased significantly during follow up, although tricuspid annular diameter did not. RV ejection fraction improved (by 9% compared with baseline, p < 0.05) and RV systolic pressure decreased significantly (from 33 (8) mm Hg to 24 (6) mm Hg, p < 0.001) after closure. CONCLUSION: MRI studies showed significant improvement of RV volumes, mass, and function after transcatheter closure of ASDs. Restoration of the RV leads to decreased pulmonary pressure resulting in a better functional class in the majority of patients.

Two distinct mechanisms mediate a differential regulation of protein kinase C isozymes in acute and prolonged myocardial ischemia.

An activation of protein kinase C (PKC) in acute myocardial ischemia has been shown previously using its translocation to the plasma membrane as an indirect parameter. However, whether PKC remains activated or whether other mechanisms such as altered gene expression may mediate an isozyme-specific regulation in prolonged ischemia have not been investigated. In isolated perfused rat hearts, PKC activity and the expression of PKC cardiac isozymes were determined on the protein level using enzyme activities and Western blot analyses and on the mRNA level using reverse transcriptase-polymerase chain reaction after various periods of global ischemia (1 to 60 minutes). As early as 1 minute after the onset of ischemia, PKC activity is translocated from the cytosol to the particulate fraction without change in total cardiac enzyme activity. This translocation involves all major cardiac isozymes of PKC (ie, PKCalpha, PKCdelta, PKCepsilon, and PKCzeta). This rapid, nonselective activation of PKCs is only transient. In contrast, prolonged ischemia (>/=15 minutes) leads to an increased cardiac PKC activity (119+/-7 versus 190+/-8 pmol/min per mg protein) residing in the cytosol. This is associated with an augmented, subtype-selective isozyme expression of PKCdelta and PKCvarepsilon (163% and 199%, respectively). The specific mRNAs for PKCdelta (948+/-83 versus 1501+/-138 ag/ng total RNA, 30 minutes of ischemia) and PKCepsilon (1597+/-166 versus 2611+/-252 ag/ng total RNA) are selectively increased. PKCalpha and PKCzeta remain unaltered. In conclusion, two distinct activation and regulation processes of PKC are characterized in acute myocardial ischemia. The early, but transient, translocation involves all constitutively expressed cardiac isozymes of PKC, whereas in prolonged ischemia an increased total PKC activity is associated with an isozyme-selective induction of PKCepsilon and PKCdelta. Whether these fundamentally different activation processes interact remains to be elucidated.

Blockade of A1 adenosine receptors prevents the ischaemia-induced sensitisation of adenylyl cyclase: evidence for a protein kinase C-mediated pathway.

OBJECTIVE: Acute myocardial ischaemia leads to a transient sensitisation of adenylyl cyclase which may contribute to the occurrence of malignant arrhythmias and the propagation of myocardial necrosis. It is prevented by blockade of protein kinase C (PKC) which is activated in early ischaemia as shown by its translocation from the cytosol to the plasma membranes. Translocation of PKC may also occur in ischaemic preconditioning, a process thought to be induced by activation of adenosine A1 receptors. In this study it was investigated whether A1 adenosine receptors may be involved in the sensitisation of adenylyl cyclase and the activation of PKC induced by ischaemia. METHODS: Isolated rat hearts were perfused with the specific A1 adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 microM) or adenosine (1 microM) prior to ischaemia induced by stop of perfusion for 5 and 10 min. Adenylyl cyclase activity was determined in plasma membranes stimulated by forskolin or stimulated via beta-receptors by isoproterenol. Total PKC activity was measured in purified plasma membranes and in the cytosolic fraction using histone III-S as a substrate. RESULTS: Myocardial ischaemia induced a beta-receptor-independent sensitisation of adenylyl cyclase (forskolin-stimulated activity 515+/-55 vs. 384+/-30 pmol/min/mg protein) which was completely blocked by pre-perfusion with DPCPX (385+/-23 vs. 386+/-24 pmol/min/mg protein). DPCPX alone did not alter the responsiveness of adenylyl cyclase to stimulation. The stimulated adenylyl cyclase activity was increased by 20 % after pre-perfusion with adenosine, mimicking the ischaemia-induced sensitisation. The effect of adenosine was not augmented by additional ischaemia. PKC activity was translocated from the cytosol to the plasma membranes by acute ischaemia, indicating an activation of the enzyme. This effect was completely abolished by DPCPX. CONCLUSION: These data demonstrate that in the rat heart the sensitisation of adenylyl cyclase in acute myocardial ischaemia is dependent on activation of A1 adenosine receptors. It is suggested that the sensitisation of adenylyl cyclase by adenosine or ischaemia might be mediated by an activation of PKC.

The cardiac adrenergic system in ischaemia: differential role of acidosis and energy depletion.

OBJECTIVE: Acute myocardial ischaemia has been shown to modulate the beta-adrenergic system and to activate protein kinase C. The aim of this study was to investigate if two important components of ischaemia, i.e. energy depletion or acidosis, may contribute to these changes. METHODS: Isolated rat hearts were perfused either with anoxia (in the absence of oxygen) or with cyanide in the absence of glucose as models of energy depletion with a loss of high energy phosphates. Alternatively, isolated hearts were perfused with acidic modified Krebs-Henseleit solution to induce acidosis. RESULTS: Energy depletion induced by cyanide perfusion leads to an increase of beta-adrenergic receptors (81 +/- 7 vs. 50 +/- 3 fmol/mg protein, p < or = 0.05) comparable to the changes observed in ischaemia, yet without any change of total adenylyl cyclase activity or protein kinase C activity. Similar, yet less pronounced changes were induced by anoxic perfusion. Acidic perfusion, in contrast, promotes a translocation of protein kinase C to the plasma membranes, suggesting its rapid activation. Additionally, an increased total forskolin-stimulated activity of adenylyl cyclase (515 +/- 16 vs. 428 +/- 17 pmol/min/mg, p < or = 0.05) was observed. Both were comparable to the sensitization observed in early ischaemia. In acidosis, the density of beta-adrenergic receptors remained unaltered. CONCLUSIONS: These data suggest that the regulation of cardiac beta-adrenergic receptors is susceptible to energy depletion, but not to acidosis, whereas the intracellular enzymes both adenylyl cyclase and protein kinase C may be regulated by intracellular acidosis. This is the first differentiation of distinct components of ischaemia modulating the beta-adrenergic signal transduction pathway. Both components may be operative in concert in acute myocardial ischaemia and may contribute to the regulation of these components of signal transduction observed in acute ischaemia.

Biliary lipids, lithogenic index and biliary drug concentrations during etofibrate and bezafibrate treatment.

Hypolipidemic drugs like etofibrate and bezafibrate may induce lithogenic bile and increase the risk of gallstone formation. In this study, biliary lipids, lithogenic index and biliary drug concentrations were investigated in 6 hyperlipidemic patients after cholecystectomy. Patients were treated once daily for 5 days with either 500 mg/day etofibrate or 400 mg/day bezafibrate. Hepatic bile was collected for 6 days via T-drainage in 4 hourly aliquots. In the patients treated with etofibrate, the range of the lithogenic index remained stable with 0.89-1.69 before and 0.78-1.51 after 5 day drug therapy. In the bezafibrate group, the range of the lithogenic index rose from 0.81-1.40 to 1.26-1.66 mainly as a result of an increase of biliary cholesterol concentrations. Biliary drug concentrations were substantially higher under bezafibrate treatment than under etofibrate treatment. In conclusion, the fibrate drugs, etofibrate and bezafibrate, are different with regard to lithogenicity of bile and extent of biliary excretion. The safety profile of etofibrate may be preferably compared to other fibrate drugs.

Theoretical and experimental comparison of an adjustable Y-junction switch.

An optical switch using an adjustable Y-junction structure has been designed, fabricated, measured, and analyzed. Both the experimental performance and theoretical prediction of the switch are presented. The switching section of the device consists of three arrow-shaped, field-induced waveguides that overlap in the propagation direction such that input light from the middle guide can be transferred to either of the output guides. A cross talk of less than -18 dB is measured at a wavelength of 1.06 microm in a device with a transition length of 400 microm and a branching angle of 4 degrees . Numerical simulations using the finite difference beam propagation method show that a cross talk of less than -22 dB may be achievable for these device dimensions.

Operation of an optoelectronic AlGaAs/GaAs waveguide neuron.

A novel monolithic AlGaAs/GaAs waveguide neuron is proposed and implemented with a Wannier-Stark superlattice in the core. Dynamic weighting, summing, and thresholding of signals is done by chip-level integration of modulators and a saturable absorber on a rib waveguide power combiner. At 780 nm (below the band gap) the range for synaptic weights is between 1 and -25 dB/mm for reverse bias below 7 V, and the modulation depth is 25 dB for the thresholding element. For a two-to-one neuron, the output-input range ratio is 25 dB.

Near millimeter wave characterization of dual mode materials.

Materials known to have useful properties in the IR were examined in the millimeter wave region. Their complex indices of refraction have been determined in the 90-550-GHz range. The method of determination was nondispersive Fourier transform spectroscopy. The instrument employed was a polarizing interferometer.