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Biomedical subjects

G Marx

Publications and source records attributed to G Marx.

At least 91 records · Page 5Linked to original sources

Transthoracic real-time three-dimensional echocardiography using a fan-like scanning approach for data acquisition: methods, strengths, problems, and initial clinical experience.

Three-dimensional echocardiography is an emerging clinical method to assess cardiovascular disorders. The feasibility of using a linear mode scanning (parallel slicing) for transthoracic data acquisition has been demonstrated. In this study, we evaluated the feasibility of real-time transthoracic three-dimensional imaging of the heart using a fan-like scanning mode of echocardiographic data acquisition. We used a computer-driven motor to sequentially angulate transthoracic transducers over a fan-like arc up to 90 degrees. With careful ECG and respiratory gating, we acquired basic two-dimensional data set via parasternal and subcostal windows and performed dynamic three-dimensional reconstructions. The problems encountered included the need to repeat data acquisition sequences because of transducer movement or inappropriate gain and gray scale settings. From 15 scanning sequences in four patients, we were able to use ten sets of data. These yielded good quality three-dimensional studies projecting normal valves, a stenotic mitral valve, and an atrial septal defect, in a number of novel views. The valves could be visualized from above and from below as well as in other orientations, and the detailed anatomy appraised. Spatial relationships of the atrial septal defect with inferior and superior vena cava, coronary sinus, or tricuspid annulus could be uniquely displayed through views from the right side of the heart. This technique provided adequate new imaging planes not available from two-dimensional echocardiography. This experience demonstrates for the first time that transthoracic three-dimensional echocardiography using a fan-like scanning mode of data acquisition is feasible, and that it provides adequate visualization of intracardiac structures in unique projections.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Transthoracic real-time three-dimensional echocardiography using the rotational scanning approach for data acquisition.

Transthoracic real-time three-dimensional echocardiography using the rational scanning approach for data acquisition became a feasible modality for cardiac imaging during the last 4 years. Several attempts for reconstruction of the heart have been made using different methods. In this study we evaluate the data acquisition using the rotational approach from the transthoracic window. Thirty-five children with congenital heart disease were enrolled in the study. All of them underwent complete two-dimensional and Doppler echocardiogram followed by three-dimensional reconstruction using rotational image acquisition. The rotational approach enabled us to acquire good data from subcostal, apical, and suprasternal notch positions by rotating the transducer from 0 degrees-180 degrees. Novel views of the atrioventricular valve, semilunar valve, atrial, and ventricular septi were established by spatial plane imaging from the three-dimensional echocardiography. This reconstruction enables spatial imaging of cardiac structures and deficiencies. Three-dimensional echocardiography will enhance the understanding of complex congenital heart disease.

Child↗

Enhanced comprehension of dynamic cardiovascular anatomy by three-dimensional echocardiography with the use of mixed shading techniques.

Advances in ultrasound instrumentation and computer technology provide us an opportunity to develop methods to perform three-dimensional echocardiography in patients. Optimal methods of displaying three-dimensional images are critical for the perception of depth and distances. We examined the utility of various shading techniques in volume-rendered three-dimensional images in 22 patients with a variety of cardiac defects. Distance coding, gray level gradient shading, texture shading, and mixtures of these shading techniques were used. Our observations suggest that the mixture of shading techniques portray the dynamic three-dimensional anatomy better than a single type of shading. Appropriate mix of shadings could provide dynamic three-dimensional echocardiograms of clinical utility.

Echocardiography↗

Cooperative effects in vitro on fibroblast and keratinocyte functions related to wound healing by transforming growth factor-beta and a low molecular weight fraction from hemolyzed blood.

Blood or its constituents, respectively, contain a.o. substances such as TGF-beta (transforming growth factor-beta), PDGF (platelet-derived growth factor) and other factors, which beneficially influence wound healing. Patients with perivascular disturbances and consequently with inadequate supply of the affected tissue cells often suffer from poor healing of dermal wounds. Here, various cellular functions in situations of poor supply and related to wound healing, such as proliferation, colony formation, and migration of fibroblasts, and of monolayer formation by keratinocytes were emulated in vitro by supplementing cultures with reduced amounts of serum. Computer-aided image analysis allowed to quantify the cellular reactions under normal and serum-deprived medium conditions and under the influence of a low molecular weight fraction manufactured by dialysis of hemolyzed calf blood (HD, Solcoseryl) and of TGF-beta. Both preparations are in use for the treatment of poorly healing wounds. While HD preferentially normalized the reduced viability of fibroblasts, the keratinocyte activity was enhanced by TGF-beta. Restoration of fibroblast and keratinocyte functions proved most effective when combining HD with TGF-beta.

Actihaemyl↗

Structural analysis of integrin recognition and the inhibition of integrin-mediated cell functions by novel nonpeptidic surrogates of the Arg-Gly-Asp sequence.

The pivotal role of the Arg-Gly-Asp (RGD) peptide motif in integrin-mediated cell adhesive interactions with extracellular matrix and plasma proteins stimulated the present design of nonpeptidic mimetics of this sequence. To probe the structural requirements for RGD recognition by integrins, we designed various structural mimetics of the tripeptide sequence, which consist of differentially spaced guanidinium and carboxylic groups. We now report that structures which contain guanidinium and carboxylic groups separated by an 11-carbon atom backbone mimic the distal configuration of functional RGD sequence. These compounds acquire a considerable affinity for the RGD-dependent platelet alpha IIb beta 3 integrin. As a result, these mimetics specifically inhibited platelet aggregation with an IC50 at the submillimolar range and interfered with RGD-dependent adhesion of CD4+ T-lymphocytes and metastatic tumor cells to immobilized fibronectin and vitronectin. A structural mimetic of the Arg-Gly-Glu (RGE) sequence, and structures with incorrect spacing between the functional groups, failed to inhibit these adhesive interactions. Furthermore, substitution of the guanidinium group by a primary amine abrogated the RGD-mediated biological effects. In vivo, an RGD surrogate effectively inhibited the elicitation of a delayed-type hypersensitivity reaction mediated by CD4+ T-cells, while the RGE mimetic did not. This interference suggests for a central role for RGD recognition in the regulation of immune responses. These proteolytically stable RGD mimetics may thus serve as useful therapeutic agents in versatile pathologic processes which depend on RGD recognition.

Amino Acid Sequence↗

Platelet multielemental composition, lability, and subcellular localization.

Diagnostic X-ray spectrometry (DXS), based on X-ray fluorescence, was used to quantitate directly the multiple elemental composition of washed, intact human platelets (n = 16), with the following results: K = 3.08 +/- 1.00 mg/g, Ca = 1.18 +/- 0.29 mg/g, Zn = 35 +/- 9 micrograms/g. These values show that washed platelets contain significant pools of K, Ca, and Zn, the latter some 30-60-fold higher than plasma levels. Dialysis of whole platelets against cation exchange resin (Chelex-100) did not extract Ca(II) and Zn(II) sequestered within whole cells. To identify the subcellular locale of the elements, platelet lysate was subjected to 30-70% sucrose gradient ultracentrifugation and subcellular enriched fractions were obtained. Fractions were analyzed by DXS (for elements), electron microscopy (for dense granules), and subcellular markers fibrinogen and von Willebrand factor. In contrast to Ca and K, which accumulate in the dense granules and the cytoplasm, respectively, Zn appears to be distributed in the alpha-granules (40%) and the cytoplasm (60%). The subcellular distribution of Zn(II) is discussed within the context of the sensitivity of platelet response to the availability of Zn(II) and the platelet release reactions following stimulation.

Absorption↗

Packaging zinc, fibrinogen, and factor XIII in platelet alpha-granules.

Zinc(II) accumulated by platelets has profound effects on platelet activity. This study is focused on the distribution of Zn(II) between human platelet subcellular compartments. After incubation with 86Rb+ and platelet lysis, the organelles were separated by sucrose density gradient centrifugation. Fibrinogen served as a marker for alpha-granules. 86Rb+ and factor XIII served as markers for the cytoplasmic fractions. Zn(II) was found to be distributed between the cytoplasm and the alpha-granules, with variations between different individual units. The total platelet Zn concentration and its relative subcellular distribution were dependent on its extracellular level. Incubation of platelets with 100 microM Zn(II) resulted in a twofold increase of its level in the cytoplasm and by one order of magnitude in the alpha-granules. In addition to the anticipated factor XIII activity in the cytoplasmic pool fraction, we found thrombin-inducible factor XIII activity within the alpha-granules. Immunoblotting confirmed the presence of both the a and b subunits of plasma factor XIII (a2b2 form) in the alpha-granules. As fibrinogen is not synthesized in the platelet, we propose that by virtue of their mutual binding, fibrinogen, Zn(II) and plasma factor XIII-a2b2 are simultaneously taken up into the alpha-granules by endocytosis, presumably through the vehicle of the GPIIb/IIIa fibrinogen receptor. A rationale for co-packaging these components within the alpha-granules is that Zn(II) inhibits factor XIII activity and thereby prevents the premature cross-linking of the concentrated fibrinogen prior to platelet activation and secretion. By contrast, cytoplasmic Zn(II) may increase platelet responsiveness to agonists due to its interaction with cytoplasmic modulators of platelet activity.

Blood Platelets↗

Intracardiac echocardiography in humans using a small-sized (6F), low frequency (12.5 MHz) ultrasound catheter. Methods, imaging planes and clinical experience.

OBJECTIVES: This study was designed to determine the clinical utility and feasibility of using 12.5-MHz ultrasound catheters for intracardiac echocardiography. BACKGROUND: Intracardiac echocardiography is a potentially useful technique of cardiac imaging and monitoring in certain settings. The feasibility of intracardiac echocardiography using 20-MHz ultrasound catheters in patients has been demonstrated. High resolution images of normal cardiac structures as well as cardiac abnormalities have been obtained. However, imaging has been limited by the shallow depth of field inherent in high frequency ultrasound imaging. METHODS: Intracardiac echocardiography with 12.5-MHz catheters was performed in eight mongrel dogs and 92 patients. Catheters were introduced percutaneously in 80 patients studied in the catheterization laboratory and directly into the heart in 12 patients in the operating room. Right heart imaging was performed in 68 patients and arterial and left heart imaging in 35 patients. RESULTS: When these catheters were introduced into the venous system, the right atrium, tricuspid valve, right ventricle, pulmonary valve and pulmonary artery were visualized. Pericardial effusion, intracardiac masses and atrial septal defects were correctly identified. The left ventricle, left atrium, mitral valve, aortic valve, aorta and coronary arteries could be imaged from the arterial circulation. Diseases identified included valvular aortic stenosis, subvalvular aortic stenosis and Kawasaki disease. Average imaging time was 10 min. No complications occurred as a result of intracardiac echocardiography. CONCLUSIONS: Intracardiac echocardiography with 12.5-MHz ultrasound catheters is safe and feasible; it also provides anatomic and physiologic information. This feasibility study provides a foundation for wider clinical use of intracardic echocardiography.

Adolescent↗

Kinetic and mechanical parameters of pure and cryoprecipitate fibrin.

The kinetics of formation (clot time; CT) as well as a mechanical parameter (breaking strength; BS) of fibrin were measured at various concentrations of fibrinogen. In a pure system and for a fixed level of thrombin, the CT-fibrinogen dependency was biphasic, reaching a minimum in the range 1-8 microM fibrinogen. A new parameter, [Fib]min, the minimal fibrinogen concentration required for phase change, was derived from this. The [Fib]min values of pure fibrinogen activated with thrombin, ranged between 0.15 and 0.25 microM fibrinogen. Single donor cryoprecipitate (cryo) had similar kinetics and [Fib]min value. A technique for measuring the innate breaking strength of fibrin, independently of its adhesive properties, is described. For pure fibrin activated with thrombin, the BS was a linear function of fibrinogen concentration, with numeric values for the slope of 0.84 g/microM and slopeCa (with 2.5 mM Ca) of 2.26 g/microM, which transformed into a general description of the BS of fibrin and the fibrinogen level according to the equation: BS = mu [Fib]. The constants mu = 18.9 dyne/microM-cm2 and microCa = 55.7 dyne/microM-cm2 reflect the innate strength of fibrin clot per cross-section area. Cryo fibrin exhibited a BS equivalent to its fibrinogen level in a pure system. Although scanning electron microscopy of pure and cryo fibrin formed at equivalent fibrinogen levels revealed significant ultrastructural disparity between the pure and cryo fibrin, the kinetics of formation and the mechanical parameters of both were comparable.

Bleeding Time↗

Model for the regulation of platelet volume and responsiveness by the trans-membrane Na+/K(+)-pump.

The correspondence between K+ uptake in platelets to their responsiveness was studied using 86Rb+ as an analogue of K+. An average 86Rb+ uptake rate of 0.73 (+/- 0.140) x 10(-15) mole Rb+/min-plt (n = 20) was observed. By the use of K(+)-influx inhibitors, we were able to distinguish three distinct 86Rb+ uptake pathways: an ouabain-sensitive (61% +/- 2% inhibitable) pump and two equivalent channels, only one of which is sensitive to furosemide. Other platelet parameters were also examined in conjunction with K(+)-uptake. Platelets incubated with ouabain exhibited an overall rise in their cell volume (MPV) with incubation time (delta MPV = 7.4 x 10(-17) L/min-1 plt-1). Concomitantly, over 24 hours, a steady decrease in platelet number was recorded by blood cell coulter, which correlated inversely with the counts of particles, which by their size resemble white blood cells (r = 0.89). On a cellular level, incubation with ouabain induced greater expression of surface fibrinogen-receptor (GPIIb), increased binding of FITC-labelled fibrinogen, and increased responsiveness to ADP. Our observations suggest the following sequence of events: Ouabain turns off the Na+/K(+)-ATPase pump, which leads to water accumulation in platelets and concomitant increased MPV. Greater expression of fibrinogen receptors on the distended platelet surface corresponds to spontaneous microaggregate formation as well as greater responsiveness to agonists. Our model links volume regulation, the expression of fibrinogen receptors, and the sensitivity of platelets to agonists to the activity of the Na+/K(+)-ATPase pump.

Blood Platelets↗

[Iatrogenic diagnostic delay in rectal cancer].

From a case material of 151 rectal carcinoma patients it has been established that the duration of anamnesis from the first consultation of the doctor to the onset of treatment was in 40 percent of the cases longer than 3 months, and in 17 percent of the cases, longer than 6 months. Only 36 percent of the patients with clinically manifest disease underwent diagnosis within a month following the first consultation of the doctor; in 37 and 15 percent of the cases, diagnosis was made only after 3 and 6 months, respectively. The causes of iatrogenic delay of diagnosis are analyzed and demonstrated by typical examples.

Diagnosis, Differential↗

Nutritional zinc increases platelet reactivity.

After ingestion of 220 mg zinc sulfate, platelet aggregation was evaluated at various time intervals (i.e., T = 0, 1, and 3 hr) and the autologous plasma analyzed by atomic absorption analysis. The zinc levels increased maximally some 0.4 +/- 0.2 microgram/ml within 3 hr after ingestion, which for the entire blood pool corresponds to only 5% of the ingested zinc. Aggregation responses of platelet rich plasma (PRP), instigated with suboptimal levels of thrombin (less than 0.2 U/ml), ADP (less than 2 microM), epinephrine (less than 2 microM), collagen (less than 2 micrograms/ml), or PAF (less than 50 ng/ml), show significant improvement to at least one aggregant. Mean +/- SEM values for delta % aggregation increase are as follows: thrombin, 51 +/- 10%; epinephrine, 21 +/- 6%; ADP, 31 +/- 6%; collagen 23 +/- 6%; and platelet aggregating factor (PAF), 56 +/- 6%. For controls, the platelets from one individual with Glanzmann thrombasthenia as well as four undosed volunteers exhibited no significant changes in platelet responsiveness. Increased platelet responsiveness to agonists after zinc sulfate ingestion was observed in PRP from blood collected in either citrate or heparin. We demonstrate that within a relatively short time period, single bolus of nutritional zinc intake can significantly increase platelet reactivity. These findings show that nutritional zinc availability is relevant to hemostasis and may pertain to the viability of platelet concentrates in blood banks.

Adenosine Diphosphate↗

The effects of aprotinin on hemostatic function during cardiac surgery.

The mechanism of action by which large doses of aprotinin decrease blood loss during cardiac surgery is not completely understood. In a prospective, controlled study, 30 patients undergoing cardiac surgery were given high-dose aprotinin in accordance with a commonly used regimen. Twenty untreated but otherwise comparable patients served as the control group. The effects of aprotinin therapy during cardiopulmonary bypass on coagulation parameters, the kallikrein-kinin system, fibrinolysis, platelet stimulation, and the release of elastase from neutrophils were studied. The fibrinolysis parameters were the only measurements that showed clear and significant differences between the two groups. Aprotinin almost completely inhibited the formation of fibrin and fibrinogen degradation products. It is assumed that inhibition of systemic fibrinolysis and suppression of local fibrinolysis contribute to the hemostatic action of aprotinin. The study did not demonstrate a significant protective effect of aprotinin on platelets. In addition, the dose of aprotinin administered did not affect the kallikrein-kinin system of elastase. Therefore, these data suggest that the previously demonstrated hemostatic effects of aprotinin derive primarily from its antifibrinolytic action.

Aged↗

Reducing white cells in platelet units.

White cells (WBCs) constitute a significant contaminant of platelet concentrates (PCs). Various technologies, including apheresis and filtration, are currently being developed to minimize the carryover of WBCs into platelets. The aim is to reduce contamination of less than 10(8) WBCs per platelet unit. As part of quality control monitoring of the blood bank operations, the centrifugation protocols employed in the preparation of platelet-rich plasma (PRP) have been evaluated for their impact on the WBC content of the PCs. The WBC content, which is expressed throughout the PRP volume as well as in the PC, reflects the degree of braking. For example, after centrifugation (2500 rpm, 4 min) of whole blood into packed red cells (RBCs) and PRP, braking-induced mixing increases the WBC content of the expressed PRP. Variations in the braking rates of the centrifuges used also correlate with the WBC carryover into packed platelets. An alternative centrifugation protocol to minimize WBC carryover is suggested. Whole blood is centrifuged at 2500 rpm for 1.5 minutes (rather than 4 min) and allowed to stop with no braking. This procedure adds some 3 minutes to the total centrifugation time, but the relative integral of this centrifugation program is approximately 50 percent smaller than that of the normally employed centrifugation protocol (with braking). It was observed that the WBC content throughout the expressed PRP, or in the entire PC, is reduced by about 75 percent. These results show that an effective method of significantly decreasing the WBC content of platelet units is simply to prepare PRP with reduced centrifugation time and with the braking programs disengaged.

Blood Platelets↗

In vivo measurement of force in the ureter. I. Basics of a new measurement principle.

A new device for the simultaneous in vivo measurement of pressure and developed force in the ureter is introduced. The 5-French catheter was cystoscopically inserted into the ureters of 12 dogs under anesthesia. The forms of the peristaltic waves for pressure and force show considerable differences. A basal force analogous to the basal pressure is only rarely measurable. During the systole, the developed force describes the pure muscle contraction process. The results are dependent on the location of the probe. Our new method is able to give information about the extent to which a ureter possesses the capacity to effectively close its lumen. This function, which is so decisive in urinary transport, can be determined not only qualitatively but also quantitatively.

Animals↗

Immunological monitoring of Fenton fragmentation of fibrinogen.

Fibrinogen is transformed into insoluble "neofibe" by reaction with up to 100 microM Cu(II) and 1.5 mM ascorbate. The soluble peptides which are released during the reaction can be monitored by amino acid analysis and by measuring released keto-carbonyl (with DNPH). Immunologic characterization of the soluble peptides, with antibodies directed against fibrino-peptide A (FPA) clearly show the release of this epitope, optimally at 50 microM Cu(II). Anti-FPB gives no evidence of that epitope. However, N-terminal amino acid analyses reveals the presence of 3 peptides terminating in ALA (alpha chain FPA), GLU (beta chain FPB) and SER/ASP (unknown). The release of fibrinopeptides is interpreted within the context of a general mechanism for OH'-induced peptide chain cleavage via intermediate Schiff-base hydrolysis.

Enzyme-Linked Immunosorbent Assay↗