[Is standard-echocardiography sufficient for identification of responders?]. / Reicht die Standard-Echokardiographie zur Identifizierung von Respondern aus?

During recent years cardiac re-synchronization has become an important tool in the treatment of patients with signs and symptoms of heart failure and de-synchronized contraction of the heart. This article describes the pathophysiological basis of de-synchronized contraction due to left bundle branch block and the use of conventional echocardiography to unmask whether the electrical abnormality is accompanied by an asynchronous contraction in the individual patient. The altered contraction in the de-synchronized heart is analysed on different levels: atrioventricular dyssynchrony describes the disturbed mechanical coupling of the ventricles and atria, interventricular dyssynchrony describes the disturbed mechanical coupling of the left and right ventricle, and intraventricular dyssynchrony describes the uncoordinated contraction of the left ventricle. Since tissue Doppler imaging is implemented only in the top level echo machines of the respective manufacturers, this article uses parameters derived from standard echo techniques to analyse the different aspects of dyssynchrony.

Comparison of dobutamine stress magnetic resonance, adenosine stress magnetic resonance, and adenosine stress magnetic resonance perfusion.

BACKGROUND: Dobutamine stress MR (DSMR) is highly accurate for the detection of inducible wall motion abnormalities (IWMAs). Adenosine has a more favorable safety profile and is well established for the assessment of myocardial perfusion. We evaluated the diagnostic value of IWMAs during dobutamine and adenosine stress MR and adenosine MR perfusion compared with invasive coronary angiography. METHODS AND RESULTS: Seventy-nine consecutive patients (suspected or known coronary disease, no history of prior myocardial infarction) scheduled for cardiac catheterization underwent cardiac MR (1.5 T). After 4 minutes of adenosine infusion (140 microg x kg(-1) x min(-1) for 6 minutes), wall motion was assessed (steady-state free precession), and subsequently perfusion scans (3-slice turbo field echo-echo planar imaging; 0.05 mmol/kg Gd-BOPTA) were performed. After a 15-minute break, rest perfusion was imaged, followed by standard DSMR/atropine stress MR. Wall motion was classified as pathological if > or =1 segment showed IWMAs. The transmural extent of inducible perfusion deficits (<25%, 25% to 50%, 51% to 75%, and >75%) was used to grade segmental perfusion. Quantitative coronary angiography was performed with significant stenosis defined as >50% diameter stenosis. Fifty-three patients (67%) had coronary artery stenoses >50%; sensitivity and specificity for detection by dobutamine and adenosine stress and adenosine perfusion were 89% and 80%, 40% and 96%, and 91% and 62%, respectively. Adenosine IWMAs were seen only in segments with >75% transmural perfusion deficit. CONCLUSIONS: DSMR is superior to adenosine stress for the induction of IWMAs in patients with significant coronary artery disease. Visual assessment of adenosine stress perfusion is sensitive with a low specificity, whereas adenosine stress MR wall motion is highly specific because it identifies only patients with high-grade perfusion deficits. Thus, DSMR is the method of choice for current state-of-the-art treatment regimens to detect ischemia in patients with suspected or known coronary artery disease but no history of prior myocardial infarction.

A small interventional device to occlude persistently patent ductus arteriosus in neonates: evaluation in piglets.

OBJECTIVES: We attempted to evaluate the efficacy and tissue reaction of a new miniature interventional ductal occlusion device in neonatal pigs. BACKGROUND: A variety of devices are used to close persistent ductus arteriosus (PDA) by interventional measures. Because of the size of these devices, they have not been applied to term or preterm neonates. Newborn piglets are comparable in size and fragility to human term and preterm neonates. METHODS: Memory-shaped double-cone stainless steel coils were mounted on a titanium-nickel core wire. A snap-in mechanism attaches the coil to the delivery wire, allowing intravascular coil retrieval and repositioning. The system was placed through a 3F Teflon catheter. Two piglet models of PDA were used: 1) ductal patency maintained by stents (n = 6), and 2) ductal patency produced by angioplasty (n = 7) to avoid stent-coil interaction. RESULTS: Placement of the coils within the PDA was possible in all piglets. Before final detachment, the coils were retrieved or repositioned, or both, up to eight times. In all but two piglets the ductus was closed within 1 h of the procedure. The coils were never dislocated and caused no infections or relevant aortic and pulmonary artery obstruction (95% confidence interval for missing complications [0 of 13] extends to 23%). Histologic and electron microscopic studies revealed endothelial coverage of the implants and histiocytic reaction but no local or systemic inflammation or erosion of the implant. CONCLUSIONS: The device was effective in experimental models of PDA. The information obtained warrants initial trials of the device in neonates.

Molecular biology of angiotensin receptors and their role in human cardiovascular disease.

The actions of angiotensin II in the cardiovascular system are transmitted by two known and possibly some unknown angiotensin receptor types. AT1 and AT2 both correspond to G-protein-coupled receptors with seven hydrophobic transmembrane domains, several N-glycosylation sites and a potential G-protein binding site. Cloning of coding regions and promoter sequences contributed to the understanding of receptor protein function and regulation. Angiotensin receptors with atypical binding properties for the known AT1- and AT2-specific ligands are expressed on human cardiac fibroblasts and in the human ulcrus. In several animal models, receptors with high affinity for angiotensin (1-7) have been described. AT1 stimulation is mediated by the generation of phospholipid-derived second messengers, activation of protein kinase C, the MAPkinase pathway and of immediate early genes. Recently, phosphorylation and dephosphorylation of tyrosine kinases have been associated with AT1- and AT2-mediated signal transduction. ATR are regulated by phosphorylation, internalization, modification of transcription rate and mRNA stability. Regulation is highly cell and organ specific and includes upregulation of ATR in some pathophysiological situations where the renin angiotensin system is activated. Whereas the function of AT1 in the cardiovascular system is relatively well established, there is little information regarding the role of AT2. Recent hypotheses suggest an antagonism between AT1 and AT2 at the signal transduction and the functional level. Transgenic animal models, particularly with targeted disruption of the AT1 and AT2 genes, suggest the contribution of both genes to blood pressure regulation. Genetic polymorphisms have been described in the AT1 and AT2 gene or neighbored regions and are used to analyze the association between gene defects and cardiovascular diseases. AT1 antagonists are now being introduced into the treatment of hypertension and potentially heart failure, and more interesting pharmacological developments are expected from the ongoing basic studies.

Angiotensin II directly increases transforming growth factor beta1 and osteopontin and indirectly affects collagen mRNA expression in the human heart.

OBJECTIVES: Angiotensin II (Ang II) induces fibroblast proliferation and collagen synthesis in the myocardium, but its precise mechanisms of action in human hearts are still unknown. Therefore, we investigated whether Ang II directly affects the collagen mRNA content in the human myocardium and in isolated human cardiac fibroblasts or whether the growth factors TGFbeta-1 and osteopontin are involved in this process. METHODS AND RESULTS I: In a first set of experiments, the direct effect of Ang II on collagen I, TGFbeta-1 and osteopontin mRNA content in fresh samples of human atrial myocardium was determined by the use of a short stimulation period. After 4 h, Ang II-stimulated atrial samples gave a significantly higher expression of both TGFbeta-1 (183+/-21% of control, p<0.05) and osteopontin mRNA (275+/-58%, p<0.02) than the controls. In contrast, the expression of collagen I mRNA was unchanged (95+/-8%). Stimulation with TGFbeta-1 led to an increase in collagen I and III mRNA (127+/-10%, p<0.05; 140+/-15%, p<0.02). METHODS AND RESULTS II: In a second protocol, to assess the effects of longer stimulation periods, we determined the effects of Ang II and its potential mediator TGFbeta-1 on collagen I, III and fibronectin mRNA expression and on proliferation of cultured human cardiac fibroblasts. Ang II caused a dose-dependent stimulation of proliferation but did not affect collagen I, II or fibronectin mRNA content after 24 h. In contrast, TGFbeta-1 stimulation significantly increased collagen I and III mRNA expression (124+/-5% and 128+/-5%, p<0.002). CONCLUSIONS: In the human heart, Ang II does not directly increase collagen or fibronectin mRNA, but it does increase TGFbeta-1 and osteopontin mRNA expression. Since TGFbeta-1 induces collagen I and III mRNA in atrial samples and in isolated cardiac fibroblasts, it may represent a necessary mediator of the Ang II effects in the human heart.

Angiotensin II and alpha(v)beta(3) integrin expression in rat neonatal cardiac fibroblasts.

We recently demonstrated that alpha(v)beta(3) integrins are involved in the mechanisms of angiotensin II (Ang II)-induced DNA synthesis and collagen gel contractions in rat cardiac fibroblasts (CFBs), cellular mechanisms that are relevant for cardiac remodeling. The aim of the present study was to elucidate the effect of Ang II and other growth factors on the regulation of the alpha(v)beta(3) integrins in fibroblasts from neonatal rat hearts. The alpha(v)beta(3) integrin receptor expression was significantly increased (P<0.05) at the mRNA level after treatment with Ang II, transforming growth factor-beta(1) (TGF-beta(1)), and platelet-derived growth factor (PDGF) for 8 and 16 hours. The surface expression of the alpha(v) and beta(3) integrin subunits was elevated after 32 and 48 hours (P<0.05) as determined with flow cytometry. To investigate fibroblast motility, we performed chemotaxis experiments with transwell chambers. Ang II was chemotactic for CFBs, as tested with checkerboard experiments. The chemotactic effect was concentration dependent and was completely blocked by Ang II type 1 receptor blockers but not by Ang II type 2 receptor blocker PD 123319. Ang II- and PDGF-BB-mediated chemotaxis could be significantly inhibited by RGD peptides and the blocking antibodies against alpha(v)beta(3) integrin (both P<0.01). Adhesion of CFBs to vitronectin was partially inhibited by an antibody to alpha(v)beta(3) integrin but was mainly mediated by an alpha(v)beta(5) integrin. Relevant in vivo expression of alpha(v)beta(3) integrin by CFBs was confirmed with in situ hybridization with probes for alpha(v) and beta(3) mRNA in rat hearts. The present study demonstrates that the expression of alpha(v)beta(3) integrin is augmented by Ang II, PDGF, and TGF-beta(1) in neonatal CFBs. Furthermore, this integrin is involved in the chemotaxis, motility, and adhesion of CFBs. The present findings support the current concept that integrins participate in the control of fibroblast behavior during cardiac remodeling mechanisms.

Intraluminal thrombus and bowel obstruction in acute leukemia due to bleeding Meckel's diverticulum.

Gastrointestinal bleeding from Meckel's diverticulum resulted in small bowel obstruction by thrombus in two patients with acute myelogenous leukemia during bone marrow aplasia and recovery from induction chemotherapy. Although gastrointestinal symptoms and complications are common in acute leukemia, these two cases are unique and describe a new syndrome that requires prompt recognition and surgical intervention. The complication of localized bowel obstruction by intraluminal thrombus is heretofore unreported.

Enhanced occlusion of vessels combining retrievable, detachable coils as differential electrodes with percutaneous, intravascular radiofrequency electrocoagulation. An experimental study.

RATIONALE AND OBJECTIVES: The authors evaluate the feasibility to accelerate occlusion of high-velocity flow vessels by a combination of transcutaneous coil placement and application of radiofrequency current. METHODS: Piglets (n = 8) were anesthetized and acutely instrumented via cutdowns in both carotid and one brachial arteries. Two identical cylindrically shaped coils (length, 3 mm; outer diameter, 2.4 mm; inner diameter, 1.4 mm) were mounted on titanium-nickel core wire and placed via 3-French Nylon catheters in both iliac arteries. The coils were kept connected to the delivery wire, which is isolated from the surrounding tissue by the catheter. The first-placed system served as control, the contralateral coil was connected to a radiofrequency generator closing electrical circuit via an external indifferent electrode. Angiograms via the brachial artery demonstrated the adequate placement of the coils and the status of the iliac arteries without and with current application. In 6 of the 8 cases, 25 watts of radiofrequency current were applied repeatedly over 10 seconds to the coil on one side at 4-minute intervals until occlusion was demonstrated. In 2 of 8 cases. 25 watts were applied continuously over 30 seconds. The coils were detached from the wire the catheters removed. Additional angiograms were performed after 5, 15, 45, and 60 minutes to show the patency of the control setting. RESULTS: Complete occlusion was achieved in all cases after a maximum of three consecutive applications of current for 10 seconds. The control remained patent for a minimum of 45 minutes. On gross and histologic examination the arteries on both sides remained intact. Disruption and charring occurred only after continuous application of current over 30 seconds. CONCLUSIONS: It is feasible to use detachable coils in conjunction with high-frequency electrocoagulation to promote coil fixation and accelerate occlusion of vessels with high blood flow.

A quantitative analysis of palliative care decisions in acute nonlymphocytic leukemia.

With the increasing incidence of cancer in elderly patients, decisions to adopt palliative care become particularly relevant to this patient population. In order to define characteristics of decisions to adopt palliative care, including those factors influencing whether a particular patient received palliation, the frequency of this therapeutic posture, and the duration of this treatment period, we performed a retrospective analytical survey of all patients with acute nonlymphocytic leukemia (ANLL) treated at Duke University Medical Center over the past ten years. Logistic regression analysis identified several potentially significant variables influencing the decision to adopt palliative care. Using a stepwise logistic model, the only independent variable associated with adoption of palliative therapy was initial treatment off a research protocol (P = 0.0001). Initial treatment off a research protocol was itself associated with older age (P = 0.0002), nonspontaneous onset of leukemia (P = 0.005), female sex (P = 0.003), and the absence of dependent children (P = 0.01) when examined by multivariate logistic regression. The palliative treatment interval was defined as the time between the discontinuation of aggressive treatment and the patient's death. Fifty-one percent, 119 of 235 patients, received palliative care; of these, 47% were palliated from the time of diagnosis and 53% were palliated only after receiving remission induction therapy. The median duration for the palliative care period was 46 days (50 days for the initially palliated group, 24 days for the group receiving aggressive therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence that Borrelia burgdorferi immunodominant proteins p100, p94 and p83 are identical.

Recently there have been reports on high-molecular mass components of Borrelia burgdorferi, namely the p100, p94 and p83, which claimed these proteins to be specific marker antigens for the serodiagnosis of late Lyme borreliosis. The nucleotide sequences of the p100 and p83 have been published. The alignment of the deduced N-terminal amino acid sequences with the N-terminal sequence of the p94 now provides evidence that all three proteins are identical.

A comparison of the inhibitory effects of taurine and GABA on identified Purkinje cells and other neurons in the cerebellar cortex of the rat.

The microiontophoretic application of taurine and GABA was studied in the cerebellar cortex of the rat. Both taurine and GABA produced a dose-dependent depression of spike frequency of cerebellar neurons. GABA (2-42 nA, mean 27 nA) induced an inhibition of spike discharge on all 138 cells tested, including 29 Purkinje cells. Taurine (60-200 nA, mean 108 nA) induced an inhibition of spike discharge on 93 of the 106 cerebellar neurons tested, including inhibition on 22 of 25 Purkinje cells. Iontophoretic application of bicuculline and picrotoxin antagonized the inhibitory effects of both GABA and taurine on Purkinje cells as well as on cerebellar neurons in general. Strychnine did not antagonize the inhibition of either GABA or taurine. Simultaneous application of taurine and GABA produced a synergistic inhibitory effect on the firing rate of Purkinje cells. Taurine, in contrast to GABA, appeared to be more depressant when applied in the Purkinje cell dendritic zone than when applied near the soma. The data are discussed in terms of taurine functioning as a neurotransmitter in the cerebellum of the rat and having receptor sites distinct from those for GABA.

Progressive outer retinal necrosis syndrome in a lymphoma patient with good visual outcome.

PURPOSE: To report an HIV-negative lymphoma patient who developed progressive outer retinal necrosis syndrome and who had a good visual outcome after treatment with two-drug antiviral therapy and intravenous immunoglobulin. METHODS: Case report. RESULTS: A 43-year-old man with small lymphocytic lymphoma was diagnosed with progressive outer retinal necrosis in his left eye. Treatment was initiated with intravenous foscarnet and ganciclovir as well as intravenous gammaglobulin at a dose of 0.5 gm/kg per day for 5 days. On the second hospital day he was started on decadron 4 mg orally four times daily. No further posterior retinitis progression was observed despite severe immunosuppression. Visual acuity remained stable at 20/30 with 10 months' follow-up. CONCLUSIONS: The benefit of using gammaglobulin in progressive outer retinal necrosis is unknown. Given the rapid improvement seen in this patient's retinitis, it may be reasonable to consider the use of gammaglobulin in other cases of infectious retinitis in immunocompromised patients.

Intramedullary spinal cord tumors resected with CO2 laser microsurgical technique: recent experience in fifteen patients.

We have operated upon 15 intramedullary spinal cord tumors with the aid of a CO2 laser attached to the microscope. The operative technique is described. Most of the tumors were localized within the cervical spinal cord. Nine tumors were benign gliomas: 4 ependymomas, 1 subependymoma, 3 astrocytomas, and 1 ganglioglioma. Six were removed totally, and 3 were removed subtotally. The remaining 6 tumors consisted of 3 hemangioblastomas, 1 intramedullary neurofibroma, 1 lipoma, and 1 primary intramedullary melanoma. Neurological function postoperatively compared to the preoperative function of the upper extremities was unchanged in 13 patients (86.5%), improved in 1, and worse in 1 patient. In the lower extremities, the preoperative neurological status was unchanged in 11 patients (73.3%), improved in 1 patient, and worse in 3 patients (20%). Magnetic resonance imaging was superior to myelography and computed tomography in localizing these lesions. Enhancement with paramagnetic substances (e.g., gadolinium-DTPA) helps to localize solid tumor within cysts. Histological evaluation of small tissue biopsies or frozen section histology is unreliable. The entire lesion should be exposed in all cases, and an attempt should be made to remove the tumor totally or, if this is not possible, to resect as much of the center of the tumor as is possible until the cord is decompressed. The decision to administer further treatment is based on the histological features of the tumor.

Intracranial melanoma metastases: surgical treatment and follow-up of 18 patients.

Eighteen patients with operated cerebral metastases from malignant melanoma were followed-up. There was no operative death and in general the patients' quality of life was improved. The results suggest that operation of a cerebral metastasis prolongs the survival of the patient if no other cerebral lesions develop. Every operatively accessible recurrence or new metastasis should be operated on, if the general condition of the patient allows it.

Painful palmar and plantar erythema associated with hepatic artery infusion of 5-fluoro-2'deoxyuridine.

Painful palmar and plantar erythema is an uncommon systemic complication of chemotherapy and has been reported in association with methotrexate, cystosine arabinoside, doxorubicin, and 5-fluorouracil. The authors report a case in which the syndrome was precipitated by hepatic artery infusion of 5-FUdR. The previous recommendation that treatment of patients developing painful palmar-plantar erythema from other drugs may be successfully resumed using intrahepatic arterial infusion of FUdR must be reconsidered in light of the present report.

[Technical principles for removal of femoral bone cements in hip prosthesis implant revision]. / Technische Prinzipien zur Entfernung femoralen Knochenzements in der Revisionshüftendoprothetik.

As the removal of femoral bone cement is one of the most challenging tasks in cemented total Hip Revision, a lot of different technical devices have been developed to aid the surgeon. All of their pros and cons are partly consequences of the specific system-design but mainly arise from the basic physical principles used. The known methods and devices as well as their data-handling have therefore been analysed, reduced to their principles according to the criteria of systematic engineering design and systematized in order to provide a better comparability and starting point for the development of new devices.

[A new coating method for cemented femur shaft implants--biocompatibility, stability during sterlization and adhesive strength]. / Eine neue Beschichtungsmethode für zementierte Femurschaftimplantate--Biokompatibilität, Sterilisierbarkeit und Verbundfestigkeit.

The main cause of aseptic loosening of cemented stems in total hip arthroplasty is the hydrolytic degradation of the metal-cement interface. In order to prevent this debonding a new multilayer method of coating the implant surface involving the use of a silica-/silane technique to create a durable adhesive bond between metal stem and bone cement has been developed. The biocompatibility of all the elements of the multilayer system was confirmed using a human osteoblast cell culture test. For sterilization purposes, gamma irradiation with a 25 kGy effective dose proved to be the method of choice. The proven biocompatibility and successful sterilization of the coated implants are the main prerequisites for in-vivo usage. On the technical side, the bonding effectiveness of the multilayer coating system was demonstrated by the tensile test, which revealed a significant improvement in the adhesive strength of the cement-metal bond under prolonged moist conditions similar to those met with in the human body.

Use of angiotensin II antagonists in human heart failure: function of the subtype 1 receptor.

THERAPEUTIC INHIBITION OF ANGIOTENSIN II: In human heart failure, specific inhibition of the cardiac effects of angiotensin II in addition to inhibition of the circulating renin-angiotensin system is an important therapeutic goal. Angiotensin II receptor subtype 1 (AT1) antagonists have been developed to specifically and selectively block the AT1 receptor and provide a more complete blockade of angiotensin II production with a marked improvement in side effects. RESULTS OF CLINICAL STUDIES: Clinical studies have shown beneficial effects from AT1 receptor antagonists. In a single dose study in patients with heart failure, the AT1 antagonist losartan decreased mean arterial pressure and pulmonary arterial pressure and increased the cardiac index, with maximal effects at 25 mg/day. The administration of losartan for 12 weeks also produced favorable hemodynamic and clinical results. The neurohormonal effects of AT1 receptor antagonists lead to decreases in plasma norepinephrine, aldosterone and atrial natriuretic peptide and an increase in plasma angiotensin II levels. EFFECT OF RECEPTOR SUBTYPE: The direct myocardial effects of angiotensin II and AT1 receptor antagonists in human hearts are determined by angiotensin receptor subtypes, their localization and regulation. We found that the receptor subtype AT2 represents the dominant receptor in normal and failing human myocardium. Angiotensin II receptors were found on isolated human cardiac fibroblasts where angiotensin II stimulated cellular proliferation via an as yet undetermined subtype. In end-stage human heart failure, angiotensin II receptors are characteristically downregulated at the protein and messenger RNA level. In a chronic rat model, the AT1 receptor antagonist losartan led to a downregulation of angiotensin II receptors in the liver, kidney, adrenal cortex and medulla. Downregulation of these receptors may represent an important mechanism by which AT1 receptor antagonists and angiotensin converting enzyme (ACE) inhibitors act to inhibit the renin-angiotensin system. CONCLUSIONS: AT1 receptor antagonists may inhibit the formation of plasma and tissue angiotensin II in heart failure to some extent. They may act synergistically with ACE inhibitors to inhibit renin-angiotensin systems completely. However, more basic data are needed to understand the effects, particularly in human myocardium.

[Role of imaging in cardiac resynchronization therapy]. / Rolle der Bildgebung bei der kardialen Resynchronisationstherapie.

Several multicenter randomized clinical trials have established cardiac resynchronization as a safe and effective way to treat heart failure patients. This is reflected in the Focus Update of the European guidelines that describes a class IA indication in patients with NYHA class II-IV heart failure with LVEF≤35% and QRS≥120 ms (NYHA III/IV) or ≥150 ms (NYHA II). If applied in clinical practice, this patient selection results in ineffective treatment in about one third of patients implanted. Since the pathophysiological basis of the disease, a disorganized electromechanical function in patients with left bundle branch block (LBBB), is amenable to analysis with imaging methods, imaging has always played an important role in patient selection. None of the parameters used proved to be reliable for the prediction of cardiac resynchronization therapy success in the multicenter PROSPECT trial. Following the publication of PROSPECT in 2008, several new studies using echocardiography and cardiac magnetic resonance imaging were published. New publications are evaluated and analyzed in the context of earlier ones.