Relationship between coronary lesion morphology and inducible wall motion abnormalities.
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Coronary Disease↗
Biomedical subjects
S Wagner
Publications and source records attributed to S Wagner.
Transfusion-related bacterial sepsis.
Transfusion-related bacterial sepsis, although infrequent, is a serious and sometimes fatal transfusion complication. Several new studies confirm previous observations of the prevalence of contamination in red cell and platelet components. In addition, several recent reports have described the risk of bacterial contamination of hematopoietic progenitor preparations. Other studies have investigated potential interventions including development of alternative skin cleansing methods, alteration of whole blood storage time, cold storage of platelet suspensions, leukoreduction of red cells, development of rapid screening tests for bacteria, and a method for bacterial inactivation of platelet components. A generic approach to inactivation, such as those targeting bacterial nucleic acid, is particularly attractive because this method would not depend on the strain or source of contamination.
Bacterial Infections↗
Light-induced c-Fos expression in the mouse suprachiasmatic nucleus: immunoelectron microscopy reveals co-localization in multiple cell types.
Although light is known to regulate the level of c-fos gene expression in the suprachiasmatic nucleus (SCN), the site of an endogenous circadian clock, little is known about the identities of the photically activated cells. We used light-microscopic immunocytochemistry and immunoelectron microscopy to detect c-Fos protein in the SCN of Sabra mice exposed to brief nocturnal light pulses at zeitgeber time 15-16. Stimulation with light pulses that saturated the phase-shifting response of the circadian locomotor rhythm revealed an upper limit to the number of photo-inducible c-Fos cells at about one-fifth of the estimated total SCN cell population. This functionally defined set was morphologically and phenotypically heterogeneous. About 24% could be labelled for vasoactive intestinal polypeptide, 13% for vasopressin-neurophysin, and 7% for glial fibrillary acidic protein. The remaining 56% of c-Fos-positive cells were largely of unknown phenotype, although many were presumptive interneurons, some of which were immunoreactive for nitric oxide synthase.
Animals↗
A novel class C beta-lactamase (FOX-2) in Escherichia coli conferring resistance to cephamycins.
An Escherichia coli strain resistant to a broad spectrum of beta-lactams, including cephamycins, was isolated from a patient suffering from urinary tract infection. A resistance plasmid (pMVP-7) was transferred from the clinical isolate to an Escherichia coli recipient. Both strains produce a cefoxitin-hydrolyzing beta-lactamase focusing at pI 6.7. The phenotype was similar to that of a Klebsiella pneumoniae strain producing cephamycinase FOX-1, so primers were selected from the FOX-1 sequence to amplify the bla gene of the transconjugant. The PCR product obtained was sequenced. The percentage of identity of the deduced amino acid sequence with sequences of other AmpC-type beta-lactamases was 96.9% with FOX-1, 74.9% with CMY-1, and 67.7% with MOX-1. This new plasmid-mediated enzyme is most closely related to FOX-1 (11 amino acid exchanges). We therefore propose the designation FOX-2.
Adult↗
A prototype liver-specific contrast medium for CT: preclinical evaluation of gadoxetic acid disodium, or Gd-EOB-DTPA.
PURPOSE: The suitability of the hepatobiliary contrast medium gadoxetic acid disodium, or Gd-EOB-DTPA, for liver enhancement at computed tomography (CT) was studied. MATERIALS AND METHODS: CT attenuation levels at 120 kV were measured in samples of increasing concentrations of gadolinium (gadoxetic acid disodium) or iodine (iopromide) in aqueous solutions in vitro. In dogs, CT attenuation in the liver was measured up to 90 minutes after a single intravenous injection of 0.3, 0.5, and 0.7 mmol Gd/kg gadoxetic acid disodium (three dogs per dose group). In addition, three VX2 tumor-bearing rabbits were examined (0.7 mmol Gd/kg). RESULTS: In vitro, the CT attenuation of gadolinium is 40% higher than that of iodine if calculated per milligram of gadolinium and iodine, respectively. In dogs, the median net increase in liver enhancement was 25, 33, and 43 HU with a dose of 0.3, 0.5, and 0.7 mmol Gd/kg, respectively. The gallbladder and bile ducts became clearly visible. In rabbits, liver enhancement of 25 HU provided improved visualization of the unenhanced tumor. CONCLUSION: Because of the higher CT attenuation of gadolinium compared with iodine and because of its liver-specific uptake, gadoxetic acid disodium is a contrast medium that may improve diagnosis of pathologic liver conditions at CT.
Animals↗
Gd-EOB-DTPA and Yb-EOB-DTPA: two prototypic contrast media for CT detection of liver lesions in dogs.
PURPOSE: To characterize computed tomographic (CT) attenuation of iodine, gadolinium, and ytterbium in vitro and to study CT liver enhancement after administration of two prototypic hepatocyte-directed contrast media in dogs. MATERIALS AND METHODS: Samples with increasing concentrations of iodine, gadolinium, and ytterbium were measured for CT attenuation in a water phantom at tube voltages of 80, 120, and 137 kV. Three groups of five adult beagle dogs each received a 0.5 mmol/kg dose of either gadoxetic acid disodium (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid [EOB-DTPA]) or Yb-EOB-DTPA as intravenous infusions or Yb-EOB-DTPA as an intravenous bolus injection. RESULTS: At 120 kV, in vitro CT attenuation of gadolinium and ytterbium exceeded that of iodine by 41% and 45%, respectively, when measured at equal mass concentrations (in milligrams per milliliter of saline). In dogs, CT liver enhancement values above the precontrast liver attenuation were 32.6 HU +/- 2.3, 31.4 HU +/- 1.1, and 33.4 HU +/- 5.2 after 0.5 mmol/kg Gd-EOB-DTPA or Yb-EOB-DTPA infusion or Yb-EOB-DTPA bolus, respectively. The values were not significantly different (P > .05) CONCLUSION: Both Gd-EOB-DTPA and Yb-EOB-DTPA provide excellent CT liver enhancement in dogs. CT liver enhancement is not significantly altered by either the absorbing element (gadolinium vs ytterbium) or the mode of application (infusion vs bolus).
Animals↗
Rapid disruption of an astrocyte interaction with the extracellular matrix mediated by integrin alpha 6 beta 4 during focal cerebral ischemia/reperfusion.
BACKGROUND AND PURPOSE: Integrins participate in cerebral microvascular integrity and signaling during focal ischemia/ reperfusion. The integrin subunits alpha 1, alpha 6, and beta 1 are distributed identically on normal cerebral microvessels. Studies in epithelium indicate that integrin alpha 6 beta 4, which interacts with laminin-5 in the basal lamina/extracellular matrix, is unique. This study describes the exact location of alpha 6, beta 4, and alpha 6 beta 4 and that their responses in focal cerebral ischemia are relevant to astrocyte-matrix interactions. METHODS: The effect of middle cerebral artery occlusion and subsequent reperfusion on the microvascular expression of alpha 6 beta 4 and laminin-5 in regions of cellular injury (dUTP incorporation) was examined in 15 nonhuman primates. Well-characterized antibodies against human alpha 6, beta 4, alpha 6 beta 4, laminin-5 and laminin-1, endothelial CD31, and vascular markers were measured with computerized video imaging and laser confocal microscopy. RESULTS: Integrin alpha 6 beta 4 was localized on astrocytes where it connects with the extracellular matrix at the astrocyte-vessel interface. It represented 59.3 +/- 16.4% of alpha 6 antigen in cerebral microvessels < 100 microns in diameter. By 2 hours of ischemia, the significant reduction in alpha 6 expression (2P < .001) was accompanied by decreases in beta 4/laminin-5 (0.76 +/- 0.03 to 0.20 +/- 0.09; 2P = .001) and alpha 6 beta 4/laminin-5 (0.73 +/- 0.18 to 0.25 +/- 0.11; 2P = .001) in the region of dUTP incorporation. Parallel changes in laminin-5 and laminin-1 were less pronounced and coincided by 24 hours. CONCLUSIONS: This is the first description of a potential role of integrin alpha 6 beta 4 in the brain, where it mediates astrocyte-matrix interactions. The dramatic disappearance of alpha 6 beta 4 relative to its ligands reflects early loss of integrity between the astrocyte and the vessel wall in selected microvessels in response to ischemia.
Animals↗
Local venous thrombosis after cardiac catheterization.
Pulmonary embolism is a rare but life-threatening complication of cardiac catheterization. Underlying deep venous thrombosis (DVT) is often not detectable clinically. To determine the true incidence of DVT the authors prospectively studied 450 consecutive patients (29% women, 71% men, mean age: fifty-eight years) undergoing a diagnostic cardiac catheterization. Patients were examined clinically and by duplex sonography with a high-resolution (5 or 7.5 MHz) transducer before and twenty-four hours after catheterization before mobilization. Duplex sonography excluded complete proximal DVT in all patients. Only partial occluding thrombi (pDVT) were detected in 11 (2.4%) patients. The thrombi were always localized at the puncture site. In 2 patients a difference was found in the circumferences of the legs, but no other clinical signs of DVT were seen. With use of continuous wave (cw) Doppler sonography, only 3 of these 11 patients (27%) showed a spontaneous (s) sound. Phlebography was performed in 4/11 patients (36%). In 2 patients the diagnosis was confirmed; in 1 patient extravenous compression was assumed, and the other demonstrated a normal-appearing phlebography at the time of investigation. Logistic regression analysis yielded a 3.5 times higher risk for developing a pDVT if a venous puncture was performed in addition to arterial puncture. Furthermore a 9.8 times higher risk was found if more than one venous puncture was necessary. During the follow-up no patient developed clinical signs of pulmonary embolism. The results of this study demonstrate that DVT is a rare complication of cardiac catheterization (0/450 patients), but pDVT occurred in 2.4%. Risk factors for pDVT are the venous puncture itself and multiple puncture attempts. Clinical relevance of pDVT remains to be determined.
Cardiac Catheterization↗
A novel sodium channel mutation causing a hyperkalemic paralytic and paramyotonic syndrome with variable clinical expressivity.
A point mutation A4078G predicting the amino acid exchange Met1360Val in segment IV/S1 of the human muscle sodium channel alpha-subunit was identified in a family presenting features of hyperkalemic periodic paralysis and paramyotonia congenita with sex-related modification of expression. In this family, only one male member is clinically affected, presenting episodes of flaccid weakness as well as paradoxical myotonia and cold-induced weakness. Three female family members who have the same mutation show only myotonic bursts on EMG. We studied the functional defect caused by this mutation by investigating recombinant wild type (WT) and mutant sodium channels expressed in a mammalian cell line (HEK293) using the patch-clamp technique. With mutant channels, the decay of the sodium currents was two times slower than with WT, the steady-state inactivation curve was shifted by -13 mV, and recovery from inactivation was 1.5 times faster. High extracellular potassium (9 mM) did not affect channel gating. Single-channel measurements revealed prolonged mean open times and an increased number of channel reopenings. The results are remarkable with respect to the lack of complete penetrance usually seen with sodium channelopathies and the site of mutation that was formerly not thought to be involved in channel inactivation.
Amino Acid Sequence↗
Trends and future developments in the pharmacological treatment of acute ischaemic stroke.
Stroke stands as the third leading cause of death. It makes great demands on patients, who must not only survive the complications of the acute stages, but must cope then with the great physical and economic costs of long-term disabilities. Therefore, there is urgent need to establish generally useful regimens for the acute treatment of ischaemic stroke. Three treatment approaches are based upon pathophysiologic concepts derived from experimental work with focal cerebral ischaemia. These include pharmacologic strategies for arterial recanalisation, inhibition of inflammatory processes and neural protection. Focal cerebral ischaemia secondary to occlusion of a brain-supplying artery initiates neuronal and microvascular events, and the simultaneous processes of inflammation which further injure tissue. The use of plasminogen activators to mediate thrombus and lysis in the acute setting has been shown to be clinically beneficial. Further work with arterial reperfusion strategies is under way. Early clinical studies with polymorphonuclear leukocyte-dependent endothelial adhesion receptor antagonists are being completed, but a strategy has yet to emerge. A large effort examining the potential efficacy of agents which may stabilise or protect neurons from ischaemic injury has shown promise in experimental models, and has been translated into clinical trials. Experimental work, and limited clinical experience, have indicated that: (a) the time window for intervention is important in limiting ischaemic and inflammatory injury, and for reducing the risk of haemorrhagic transformation; (b) putative neuroprotective strategies may potentially elongate the time interval for treatment; and (c) limitations from the adverse effects of plasminogen activators and of agents which beneficially affect neuronal dysfunction during ischaemia must yet be overcome. This review surveys pharmacological approaches currently undergoing evaluation which provide the goal of establishing effective strategies for the treatment of patients with acute cerebral ischaemia.
Acute Disease↗
Liposome-encapsulated superparamagnetic iron oxide particles as markers in an MRI-guided search for tumor-specific drug carriers.
Three different types of liposomes containing superparamagnetic iron oxide particles (SPIOs) as the contrast agent were tested for intratumoral enrichment by magnetic resonance imaging (MRI). The liposome-encapsulated SPIOs were investigated in comparison with AMI-227, dextran-coated SPIOs in two different dosages using the CC531 adenocarcinoma in the liver of WAG/RIJ rats as a model. Reduction of the relative signal intensity (SI) in the tumor in T2-weighted MR images was assumed as a measure of the liposome enrichment in the tumor or adjacent tissue. The samples were tested at dosages with isomolar iron content and at dosages producing the same MR relaxivity R2. For reverse phase evaporation vesicles and small unilamellar vesicles behavior differed remarkably according to the applied dosage. A steady, strong reduction in SI, starting immediately after injection and extending up to 48 h, was observed for small unilamellar vesicles sterically stabilized with polyethylene glycol.
Adenocarcinoma↗
The spleen as a storage pool in lipid metabolism.
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Acute Disease↗
[Pulmonary melioidosis in a German Southeast Asia tourist].
HISTORY AND CLINICAL FINDINGS: A patient who returned from a 3-year stay in Thailand and India one year ago, was admitted with fever of 38.5 degrees C and productive cough for the last four weeks. He remembered wounding his foot three years ago in India with contamination by soil. Subsequently, recurrent pustulae appeared on his feet. One such pustule was found on admittance. The clinical examination showed low body weight, without further abnormalities. INVESTIGATIONS: The blood examinations revealed high inflammation parameters and ruled out any immunodeficiency. Smouldering infiltrates in the upper lobes were found on the chest radiography. Sputum was free of acid fast bacilli and no mycobacterial DNA was detected by polymerase chain reaction. Bronchoscopy showed a normal endobronchal situation, Burkholderia pseudomallei were found to grow from specimens of bronchial mucus. TREATMENT AND COURSE: Under the empirical treatment with ampicillin/sulbactam, we could not find any response. After switching to Ceftazidime and trimethoprim/sulfamethoxazol (TMP/SMZ) we observed quick clinical improvement and normalisation of the inflammation parameters and notable radiological response over three weeks. We continued a five months TMP/SMZ therapy after discharge in order to prevent relapses. CONCLUSION: For travellers and immigrants from Southeast Asia presenting smouldering infiltrations of the upper lobes, one should include Melioidosis in the differential diagnosis.
Adult↗
Postinfarction stress testing and one year outcome of stable patients after myocardial infarction treated with thrombolytics.
OBJECTIVE: The purpose of our study was to evaluate the predictive power of early postinfarction stress testing in survivors of uncomplicated MI treated with thrombolytics. METHODS: The study population consisted of 102 consecutive, thrombolyzed survivors (56 +/- 11 years) of acute, transmural myocardial infarction with uncomplicated postinfarction course. All patients were clinically stable in the postinfarction period and underwent cycle ergometry, 99mTc perfusion scintigraphy and dobutamine stress-echocardiography within three weeks after the acute event. Coronary angiography was used to determine the extent of CAD, LV ejection fraction (LVEF), TIMI grade and residual stenosis of the infarct-related coronary artery. A follow up questionnaire was performed one year after hospital discharge to determine the relation to the occurrence of cardiac events (unstable angina, reinfarction, PTCA, bypass surgery and death). RESULTS: 30 patients developed 34 cardiac events. Four patients died. Two thirds of the 'cardiac events' in the year of follow-up were revascularization procedures mostly selected by evidence of ischemia on 99mTc perfusion scintigraphy and/or stress-echocardiography. These two methods were significantly associated with the development of new cardiac events (stress-echocardiography: p < 0.01; 99mTc perfusion scintigraphy: p < 0.006). Parameters of bicycle ergometry and variables of coronary angiography were not related to an increased risk of future cardiac events. The number of 'hard cardiac events'--death or nonfatal AMI--was too small (8%) in these patients who are able to exercise to make statistical comparisons. CONCLUSIONS: The study underlines the necessity of early noninvasive risk assessment to identify patients at a greater risk among survivors of uncomplicated AMI treated with thrombolytics who are clinically stable in the early postinfarction period. PTCA and coronary bypass surgery is performed in one third of these patients selected mostly by evidence of ischemia on 99mTc perfusion scintigraphy and/or stress-echocardiography. Results of bicycle ergometry are of limited value in these patients within the first year after acute myocardial infarction.
Coronary Angiography↗
Electronic Transport Processes in Heavily Doped Uncompensated and Compensated Silicon as Probed by the Thermoelectric Power.
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Journal Article↗
Intraindividual comparison of three stress tests during the early postinfarction period in stable patients with thrombolysis.
The intention of the study was to intraindividually compare the ischemic yield of three stress tests early after acute myocardial infarction. At a large community hospital 107 stable patients who survived acute transmural myocardial infarction after thrombolytic therapy followed by an individual optimized medical treatment, were prospectively investigated by three noninvasive stress tests. All patients received bicycle ergometry, 99mTc perfusion scintigraphy and stress-echocardiography within three weeks after the acute event. Each patient underwent diagnostic cardiac catheterization for determination of angiographic data. 99mTc perfusion scintigraphy had the highest rate of positive test results (61%), as compared to bicycle ergometry (32%), stress echocardiography (34%) and stress induced angina in any of the stress tests performed (40%). In 79% of the patients studied, at least one of four ischemic parameters was positive. The combination of bicycle ergometry, stress induced angina and 99mTc perfusion scintigraphy detected myocardial ischemia in 78% of the patients studied. Concordance of at least three positive parameters was seen in only 27%. Intraindividual comparison between positive and negative test results was inconclusive. Only stress-echocardiography versus stress-induced angina showed a moderate agreement (kappa = 0.44). Stress-induced angina was the only ischemic parameter which corresponded to the grade of the residual stenosis of the infarct related coronary artery (p < 0.01) and reduced left ventricular function (p < 0.005). These findings show, that concordance of three common stress tests in detecting myocardial ischemia anywhere in patients after acute transmural myocardial infarction and thrombolytic therapy is poor. Stress-echocardiography and stress inducible angina show a moderate agreement. Follow-up studies of these patients are currently performed to clarify prognostic significance and therapeutic consequences of positive test results in these patients.
Angina Pectoris↗
Evaluation of efficient chemoembolization mixtures by magnetic resonance imaging therapy monitoring: an experimental study on the VX2 tumor in the rabbit liver.
To find effective chemoembolization mixtures, we tested combinations of carboplatin with the embolizates Spherex and Gelfoam in comparison to a therapy with NaCl-solution, a treatment with the cytostatic drug only, and a therapy with each of the embolizates alone. The experiments were carried out using as a model the VX2 tumor in the liver of male chinchilla rabbits (five for each group). Carboplatin was revealed by the 3-(4,5-dimethylthiazole-2)-yl-2,5-diphenyltetrazolium bromide test to be a potent cytostatic drug for VX2 rabbit tumor cells. We used magnetic resonance imaging to examine the tumor volume and signal intensity enhancement up to 15 min after Gd-DTPA administration within the tumor and liver before and after the different therapies. These parameters allowed us to evaluate tumor growth and vitality as well as liver injury for the different therapy types. The results found by magnetic resonance imaging corresponded very well to those obtained by histological analysis of the tumors. The chemoembolization therapies were significantly more efficient than the other therapies, as indicated by the reduction of signal intensity enhancement after contrast agent administration within the tumor and by the histologically determined necrotic fraction after therapy. In addition, we found a significant decrease of the tumor volume and no significant live injury for a therapy with Carboplat and Gelfoam.
Animals↗
Differential mRNA decay within the transfer operon of plasmid R1: identification and analysis of an intracistronic mRNA stabilizer.
Processing of the transfer operon mRNA of the conjugative resistance plasmid R1-19 results in the accumulation of stable traA mRNAs. The stable traA transcripts found in vivo have identical 3' ends within downstream traL sequences, but vary at their 5' ends. The 3' ends determined coincide with the 3' base of a predicted large clover-leaf-like RNA secondary structure. Here we demonstrate that this putative RNA structure, although part of a coding sequences, stabilizes the upstream traA mRNA very efficiently. We also show that the 3' ends of the stable mRNAs are formed posttranscriptionally and not by transcription termination. Half-life determinations reveal the same half-lives of 13 +/- 2 min for the traA mRNAs transcribed from hybrid lac-traAL-cat test plasmids, the R1-19 plasmid, and the F plasmid. Protein expression experiments demonstrate that the processed stable traA mRNA is translationally active. Partial deletions of sequences corresponding to the predicted secondary structure within the traL coding region drastically reduce the chemical and functional half-life of the traA mRNA. The results presented here unambiguously demonstrate that the proposed secondary structure acts as an efficient intracistronic mRNA stabilizer.
Bacterial Outer Membrane Proteins↗