PubMed Health⌕ Search

Biomedical subjects

G Marx

Publications and source records attributed to G Marx.

At least 73 records · Page 4Linked to original sources

[Pulse oximetry and capnography in intensive care transportation: combined use reduces transportation risks].

OBJECTIVE: Due to the growing number of diagnostic and therapeutical procedures intensive-care patients must be transported intra- and interhospitally more often. These transports are among the most critical events during intensive-care therapy, with a high incidence of potentially life-threatening mishaps [23]. The aim of this study was to evaluate the possible benefit of the combined application of pulse oximetry and capnometry for patient safety during transport. METHODS: In a prospective clinical study 48 mechanically ventilated patients were allocated at random in 2 main study groups, 24 patients were investigated during interhospital transportation with an ambulance car, the other 24 patients during intrahospital transports. They were classified according to APACHE II and TISS. Blood pressure, heart rate and arterial blood gases were measured at eleven selected times. Twelve randomly chosen patients out of each main study group were monitored additionally with pulse oximetry and capnometry. The results were compared using the Mann-Whitney-U test. P < or = 0.05 was considered significant. RESULTS: Thirty-four patients had a TISS more than 40. The mean APACHE II-Score was 14 +/- 5. The overall incidence of potentially life-threatening mishaps was 9. Six out of these 9 occurred in the 24 patients with additional monitoring and were immediately detected by pulse oximetry or capnometry. CONCLUSIONS: The combination of pulse oximetry and capnometry offers the possibility to detect potentially life-threatening problems in ventilated patients during transport. This allows for early therapeutical consequences and may help to reduce the risk of transports.

APACHE↗

Covalent attachment of ethidium to DNA results in enhanced topoisomerase II-mediated DNA cleavage.

The classic DNA intercalator, ethidium, was used to probe the effects of (i) intercalation and (ii) covalent modification of the DNA on the catalytic activity of topoisomerase II. Ethidium bromide, which binds reversibly to DNA via intercalation, does not stimulate topoisomerase II-mediated DNA cleavage at concentrations up to 100 microM, indicating that the intercalative binding of this molecule to DNA is not sufficient to alter the activity of the enzyme. In contrast, covalent attachment of the photoreactive ethidium analog to DNA resulted in marked enhancement of topoisomerase II-mediated single- and double-stranded DNA cleavage. This increase in DNA cleavage was observed at very low drug binding densities (<1 drug per 10-80 base pairs) which correspond to nanomolar concentrations, as compared with other topoisomerase II poisons such as etoposide or m-AMSA which require micromolar concentrations to elicit comparable DNA cleavage levels. Over the past decade, topoisomerase II has been an important target for a variety of clinically relevant anticancer agents due to the abilities of these agents to convert this enzyme to a cellular toxin resulting in an increase in the levels of enzyme-mediated DNA breaks. Modification of DNA by covalently attaching a DNA-targeting intercalating agent (i.e., ethidium bromide) resulted in a marked shift of the cleavage/religation equilibrium of the enzyme toward the cleaved state "poison" topoisomerase II as observed by the enhancement in single- and double-stranded cleavage; thus, key insight was gained into the mechanism(s) through which DNA binding agents may influence the catalytic properties of topoisomerase II. These data demonstrate that conversion of a reversible ethidium-DNA complex to an irreversible adduct results in the transformation of an ineffective intercalating drug into a potent topoisomerase II-targeted agent. Finally, they provide support for the recently proposed "positional poisoning model" for the actions of DNA lesions and anticancer drugs on the type II enzyme.

Animals↗

Three-dimensional echocardiographic evaluation of aortic disorders with rotational multiplanar imaging: experimental and clinical studies.

Transesophageal echocardiography has become a highly valuable method to assess aortic disorders. With this method, however, aortic disease has been visualized only in two-dimensional views. Advances in computer technology have introduced three-dimensional (3D) echocardiography as a developing modality in cardiac imaging. Previous efforts to obtain 3D reconstructions of the aorta, by various techniques, had limited clinical applicability. In this study we attempted to explore the feasibility and potential of 3D reconstructions of the aorta employing a widely used multiplane transesophageal imaging technique in an experimental setting and in patients. In the in vitro study, we created 35 lesions in 28 pig aortic trees (15 aortic dissections, five saccular aneurysms, five coarctations, five atheromas, and five clots within dissections). Suspending these specimens in a water bath, sequential two-dimensional images were acquired over a 180-degree rotation with a commercially available multiplane transesophageal probe and ultrasound system with a 3D software package. Data processing (digital reformation, interpolation, and segmentation) and 3D display were accomplished on an off-line computer system. 3D reconstructions were achieved and displayed in wire-frame, surface-rendered, and volume-rendered images. These 3D reconstructions corresponded well with the actual anatomic specimens in delineating the various pathologic findings. In patient studies, we collected a total of 36 studies in both adults and children with a mean age of 44.5 years (range 1 month to 82 years). In addition to normal aortas (n = 13), the spectrum of abnormalities studied included six atheromatous lesions, four aortic dissections, 10 coarctations, one aneurysm with a thrombus, and one dilated aortic root. We were able to accomplish volume-rendered 3D images depicting the aortic lesions in their true form that could be viewed in many different perspectives in all patients. We conclude that 3D echocardiography is able to display the aorta and aortic disease in a realistic manner. Although this modality still has limitations, further improvements in computer and ultrasound technology would strengthen 3D echocardiography as a clinically viable diagnostic tool, in the evaluation of aortic disorders.

Adolescent↗

Virucidal treatment of blood protein products with UVC radiation.

The virus safety of blood derivatives continues to be of concern, especially with respect to nonenveloped and/or heat-stable viruses. Previously, we demonstrated that treatment of whole plasma, AHF concentrate or fibrinogen with short wavelength ultraviolet light (UVC) results in the inactivation of > or = 10(6) infectious doses (ID) of encephalomyocarditis virus (EMCV), hepatitis A virus (HAV) and porcine parvovirus (PPV), each of which is nonenveloped. Protein recovery was enhanced greatly by inclusion of the flavonoid, rutin, added prior to UVC exposure to quench reactive oxygen species. We now report on the treatment of albumin and intravenous immune globulin (IVIG) isolated by a previously described, integrated chromatographic method. Albumin was treated with either 0.1 or 0.2 J/cm2 UVC in the presence of 0.8 or 1.6 mM rutin; IVIG was treated with either 0.05 or 0.1 J/cm2 UVC in the presence of 0.5 or 1.0 mM rutin. Our results show that > or = 10(6.9) ID of EMCV and PPV were inactivated under each of the conditions studied except the treatment of albumin with 0.1 J/cm2 UVC in the presence of 1.6 mM rutin where 10(4.3) ID of EMCV and > or = 10(6.9) ID of PPV were killed. It appears that the sensitivity of PPV to UVC exceeds that of EMCV and that virus kill with UVC is higher in IVIG than in albumin. In the absence of rutin, UVC increased the extent of aggregation of both albumin and IVIG by two- to three-fold. With rutin present, the increase in albumin aggregation was reduced, and it was virtually eliminated by subsequent processing on Sephacryl S-200, a step in the existing procedure designed to remove aggregates. The increase in aggregation of IVIG appeared to be eliminated on inclusion of either 0.5 mM or 1 mM rutin. We conclude that both albumin and IVIG can be treated with UVC to inactivate > or = 10(6) ID of nonenveloped viruses. The inclusion of rutin during treatment helps protect against protein aggregation.

Blood Proteins↗

Evaluation of pooled fibrin sealant for ear surgery.

HYPOTHESIS: This study investigated the bonding strength and tissue toxicity of a commercially prepared dual-virally-inactivated pooled-blood fibrin tissue adhesive (ViGuard-FS; Melville Biologics, Inc., NY, U.S.A.) and compared it with an autologous fibrin tissue adhesive made by the precipitation of fibrinogen using ethanol and freezing (AFTA-E). METHODS: The bonding strength of FS was optimized by varying the concentrations of fibrinogen and human or bovine thrombin using three different surface media: inorganic (silastic), animal skin, and human dura mater. Furthermore, tissue reactions and duration of fibrin clots were studied by injecting FS into the auricles of rats. RESULTS: This study showed that optimized FS with human thrombin was superior in bonding strength to AFTA-E on all three surface media, and that FS does not produce any toxic tissue responses when injected into rat auricles. Minimal traces of the adhesive clot could be observed in a few auricles at 35 days after application. CONCLUSIONS: Because it is made from pooled-donor blood that has been treated with virus elimination procedures, FS is superior to autologous fibrin tissue adhesive in which fibrinogen is precipitated by the ethanol/freezing method. FS has not shown any undesirable tissue reactions when injected into live rat auricles. We believe that these results provide a rationale for further clinical development of ViGuard-FS as a tissue adhesive for otologic surgery.

Animals↗

[Immunosuppressive treatment of a spontaneous inhibitor hemophilia A using cyclophosphamide, vincristine and prednisone following prior Factor VIII stimulation].

A 59-year-old patient who presented with hematuria and recurrent soft tissue bleeding was found to have a factor VIII inhibitor level of 52 Bethesda units (BU)/ml and acquired hemophilia was diagnosed. After treatment with immunoglobulins (0.4 g IgG/kg per day for one week) the factor VIII inhibitor titer decreased to 12 BU/ml. Because of another episode of retroperitoneal hemorrhage, the patient was put on an immunosuppressive combination therapy which was first described by Lian et al. (1988). Our patient was infused with a factor VIII concentrate followed by cyclophosphamide, vincristine and prednisone. This regimen was repeated every 3-4 weeks. After 6 courses a further decline in the factor VIII inhibitor concentration, but no complete eradication of the autoantibody, was achieved. The factor VIII inhibitor level has remained at 2.5 BU/ml for more than 7 weeks without further bleeding episodes. The pathophysiology and treatment of acquired hemophilia are discussed.

Autoantibodies↗

Effect of fibrinogen and thrombin concentrations on mastectomy seroma prevention.

Seroma formation remains a significant clinical problem which increases morbidity and hospital costs in patients undergoing mastectomy operations. This study evaluated the effect of varying the concentrations of fibrinogen and thrombin in fibrin sealant on successfully preventing seroma formation in a rat model. After axillary dissection, control animals (Groups I and II) had 1 ml of either normal saline or thrombin (100 U/ml) applied to the axilla while treated animals (Groups III-VIII) had increasing concentrations of 0.5 ml of fibrinogen (25, 50, or 100 mg/ml) and 0.5 ml of thrombin (10 or 100 U/ml) applied. Seroma volumes (means +/- standard deviation) were measured on Postoperative Day 5. They were largest in Group I (3.1 +/- 1.9 ml, n = 13) and Group II (3.9 +/- 2.7 ml, n = 15) and then decreased from a high in Group III (2.5 +/- 2.4 ml, n = 15) using fibrinogen, 25 mg/ml, and thrombin, 10 mg/ml, to a low in Group VIII (0.8 +/- 1.0 ml, n = 15) using fibrinogen, 100 mg/ml, and thrombin, 100 U/ml. Analysis of variance revealed a statistically significant difference in the mean seroma fluid volumes between the groups (P = 0.0021), while Scheffe's comparison showed a specific significant difference (P = 0.028) between the thrombin control (Group II) and the highest concentration fibrin sealant (Group VIII). The difference in seroma volumes for all control animals (Groups I and II), 3.5 +/- 2.4 ml, and all treated animals (Groups III-VIII), 1.7 +/- 2.1 ml, was highly significant by unpaired t test. (P < 0.0001). Thus, fibrin sealant was useful in reducing seroma formation in this rat model with the highest concentration of fibrinogen and thrombin appearing most effective. These data may be useful in guiding future clinical trials in humans.

Animals↗

Volume-rendered, three-dimensional echocardiographic determination of the size, shape, and position of atrial septal defects: validation in an in vitro model.

Accurate evaluation of atrial septal defect (ASD) size and shape is very important for the selection of patients for transcatheter occlusion. The ability of volume-rendered, three-dimensional echocardiography (3DE) in displaying ASDs in a dynamic mode has been demonstrated; however, its accuracy in sizing ASDs is unknown. To assess this, we performed 3DE of 10 explanted pig hearts in which ASDs of various locations, sizes, and shapes had been experimentally created. From en face 3DE views of the atrial septum containing the defects, major and minor diameters of the defect were measured by a blinded observer, and these data were compared to direct anatomic measurements. The correlations between 3DE and anatomy for the major and minor ASD diameters were y = 0.83x + 3.4 (r = 0.97, p < 0.0001) and y = 0.92x + 1.3 (r = 0.92, p < 0.0001) respectively. The correlation between the measures for major and minor axis ratio was y = 1.06 x - 0.052, r = 0.91, p < 0.0002. Good agreement between both methods of measurements was demonstrated for all measurements. In addition, 3DE portrayed the location and shape of the defects accurately. Thus 3DE provides excellent visualization of ASD and is able to accurately define the size of the defects. These qualitative and quantitative capabilities enhance the clinical potential of this technique in the appraisal of ASDs for decisions regarding application of closure devices.

Animals↗

Protecting fibrinogen with rutin during UVC irradiation for viral inactivation.

Fibrinogen solutions were irradiated with UVC (254 nm) to inactivate contaminating viruses. In order to protect fibrinogen during UVC irradiation, 0.5 mM rutin was added prior to UVC exposure and subsequently removed during processing. Viral kill by 0.1 J/cm2 UVC resulted in the following inactivation values (log 10): non-lipid-enveloped viruses: Parvo > or = 5.5; encephalomyocarditis virus > or = 6.5; hepatitis A virus > or = 6.5: lipid-enveloped viruses: human immunodeficiency virus > or = 5.7; vesicular stomatitis virus > or = 5.7. Fibrinogen irradiated with 0.5 mM rutin did not significantly differ from unirradiated material in terms of clot time and breaking strength. In the absence of rutin, UVC irradiation of fibrinogen at similar fluence led to loss of solubility, increased clot time and the cleavage of fibrino-peptides that reacted with dinitrophenyl hydrazine as a test for ketonic carbonyl groups. High-performance liquid chromatography and mass spectrometry data showed that rutin exposed to UVC formed numerous breakdown, oxidation and combinational products. Experiments with 3H-rutin showed that after UVC irradiation, subsequent processing by a C18 resin and alcohol precipitation removed > 99% rutin, representing < 10 ppm rutin in the final fibrinogen preparations. Residual 3H-rutin was not covalently bonded to the fibrinogen. Immunochemical studies with rabbit antisera to UVC irradiated (with rutin) fibrinogen showed the absence of neoimmungens. By all measures, rutin prevents fibrinogen degradation during virucidal UVC irradiation.

Animals↗

Dynamic three-dimensional echocardiographic assessment of intracardiac blood flow jets.

Transthoracic dynamic 3-dimensional reconstruction of the heart with tissue depiction has been proved to be feasible when using various methods of data acquisition. The same method can theoretically be applied to color Doppler flows to generate dynamic 3-dimensional images of intracardiac blood flow jets. To explore the feasibility of this approach, we studied 41 patients with various valvular disorders or intracardiac shunts. We acquired sequential 2-dimensional images along with color Doppler information using rotational scanning from a transthoracic or a subcostal window. Images were digitized and processed for 3-dimensional reconstruction using dedicated software. After adequate segmentation, the flow jets were displayed in 3 dimensions in a gray scale format. With use of this approach, 3-dimensional reconstruction of color Doppler flows was possible in all but 1 patient. Still frames allowed immediate appreciation of the shape of the jets, their location in the cardiac chambers, and their size related to that cavity. Dynamic display was even more striking by showing the flow in real time. Dynamic 3-dimensional images enabled visualization of flow jets in projections not available in conventional color flow Doppler, looking directly at the views of shunt and regurgitant flows, and also permitted 3-dimensional delineation of flow convergence zones. We conclude that dynamic visualization of various intracardiac flows in 3 dimensions using transthoracic echocardiography is possible. It provides a better understanding of the shape and size of the jets, and can potentially aid in flow quantification by displaying the actual shape of flow convergence regions.

Adolescent↗