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Biomedical subjects

G Marx

Publications and source records attributed to G Marx.

At least 37 records · Page 2Linked to original sources

Recombinant erythropoietin in clinical practice.

The introduction of recombinant human erythropoietin (RHuEPO) has revolutionised the treatment of patients with anaemia of chronic renal disease. Clinical studies have demonstrated that RHuEPO is also useful in various non-uraemic conditions including haematological and oncological disorders, prematurity, HIV infection, and perioperative therapies. Besides highlighting both the historical and functional aspects of RHuEPO, this review discusses the applications of RHuEPO in clinical practice and the potential problems of RHuEPO treatment.

Anemia↗

Exacerbation of antiphospholipid antibody syndrome after treatment of localized cancer: a report of two cases.

Patients with malignancy often present with a variety of coagulation abnormalities which may ultimately lead to recurrent arterial and venous thromboses. Recently the presence of antiphospholipid antibodies in cancer patients has been proposed as one of the potential mechanisms promoting hypercoagulability. Here we report two consecutive patients with localized tumors, one suffering from breast cancer and another presenting with colorectal cancer, who experienced dramatic exacerbation of the antiphospholipid antibody syndrome (APAS) within 4 weeks after surgery. In the first patient who had also received one course of adjuvant chemotherapy, major ischemic stroke and recurrent venous thromboembolism were paralleled by the development of ulcerative livedoid vasculitis and pancytopenia, constituting the diagnosis of systemic lupus erythematosus with secondary APAS. In the second patient, progressive thrombotic occlusion of the superior and inferior vena cava was associated with bilateral pulmonary embolism, acute renal failure, and disabling soft tissue edema. Although not fulfilling the classic criteria of "catastrophic" APAS, the clinical features were life threatening and appeared to be refractory to oral anticoagulation with phenprocoumon. In addition, a diagnosis of Trousseau's syndrome was unlikely due to missing evidence of gross metastatic disease. Besides a suggested treatment strategy comprising high doses of low-molecular-weight heparin, potential pathogenic mechanisms are discussed in consideration of a recently proposed "thrombotic storm," which may cause multiple thromboses after an initial provocation in patients with known hypercoagulability.

Adult↗

Phase I study of docetaxel plus ifosfamide in patients with advanced cancer.

The aim of this study was to determine the maximum tolerated dose of a fixed dose of docetaxel when combined with continuous infusion ifosfamide, with and without G-CSF support, in the treatment of advanced cancer, and to evaluate anti-tumour activity of this combination. Thirty-one patients with advanced malignancies were treated with docetaxel 75 mg/m(2) intravenously on days 1, and ifosfamide at increasing dose levels from 1500 mg/m(2)/day to 2750 mg/m(2)/day as a continuous infusion from day 1-3, every 3 weeks. A total of 107 cycles of treatment were administered. Without G-CSF support dose-limiting toxicity of grade 4 neutropenia greater than 5 days duration occurred at dose level 1. With the addition of G-CSF the maximum tolerated dose was docetaxel 75 mg/m(2) on day 1 and ifosfamide 2750 mg/m(2)/day on days 1-3. Dose limiting toxicity (DLT) included ifosfamide-induced encephalopathy, febrile neutropenia and grade three mucositis. Three complete responses and 3 partial responses were seen. This combination of docetaxel and infusional ifosfamide is feasible and effective. The recommended dose for future phase II studies is docetaxel 75 mg/m(2) on day 1 and ifosfamide 2500 mg/m(2)/day continuous infusion on days 1-3.

Adenocarcinoma↗

Investigation of interfacial interaction between uncoated and coated carbon fibres and the magnesium alloy AZ91.

Unidirectionally reinforced metal-matrix composites with a fibre volume content between 63 and 68% were processed by squeeze casting using T800 H carbon fibres and the magnesium alloy AZ91. The surface of the fibres was prepared by thermal desizing of the fibres or by deposition of a pyrolytic carbon (pyC) coating. Different interfacial conditions could be identified by transmission electron microscopy (TEM) and the single-fibre push-in test. TEM confirmed the formation of needle-like phases at the fibre surface or, for coated fibres, within the pyrolytic carbon coating. During loading by the Vickers type indenter an intense response was observed for composites of coated fibres and the magnesium alloy. This could by caused by stick-slip effects within the pyrolytic carbon coating.

Journal Article↗

[Complicated antiphospholid antibody syndrome].

HISTORY AND CLINICAL FINDINGS: A 51-year-old female patient suffered from recurrent ischemic strokes and venous thromboembolism although treated with ASS and phenprocoumon, which mainly occurred after diagnosis and treatment of an invasive-ductal mamma carcinoma. The severely ill patient presented with right-sided hemiparesis and dysarthria, a swollen leg, a painful necrotic-ulcerative lesion at the left-lateral ankle and a systolic heart murmur. INVESTIGATIONS: Laboratory data revealed a haemoglobin of 8,4 g/dl, a leucocyte count of 3,1 x 10 (9)/l and a platelet count of 87 x 10 (9)/l. C-reactive protein, ESR and plasma fibrinogen were markedly increased. Levels of antinuclear, IgG-anticardiolipin and anti-doublestranded-DNA antibodies were excessively elevated. A test for lupus anticoagulant was strongly positive. Sonographic examinations showed deep vein thrombosis and significant mitral valve regurgitation. Suspected pulmonary embolism was demonstrated by CT scan. We diagnosed systemic lupus erythematosus with secondary antiphospholipid antibody syndrome (APAS). TREATMENT AND COURSE: Phenprocoumon was stopped and full-dose anticoagulation with low-molecular-weight heparin initiated. Additional immunosuppressive therapy consisted of cyclophosphamide, azathioprin and prednisone resulting in prevention of further thromboembolism and significant improvement of clinical symptoms. The observed severe interference of LA with the prothrombin time after cessation of phenprocoumon (INR 3,6; FII activity 81 %) suggested that the effect of oral anticoagulation had been overestimated in the past. CONCLUSION: APAS may present as an acute and life-threatening disorder. In this case interdisciplinary co-operation and a highly individualised treatment strategy are mandatory.

Antineoplastic Combined Chemotherapy Protocols↗

Hydroxyethyl starch and modified fluid gelatin maintain plasma volume in a porcine model of septic shock with capillary leakage.

OBJECTIVE: To compare the effects of different volume replacement therapies on maintenance of plasma volume in septic shock and capillary leakage syndrome. DESIGN AND SETTING: Prospective randomized, controlled animal laboratory study in a university animal laboratory. MEASUREMENTS AND RESULTS: Twenty-five fasted, anaesthetized, mechanically ventilated and multi-catheterized pigs (20.8+/-1.8 kg) received 1 g/kg body weight faeces into abdominal cavity to induce sepsis and were observed over 8 h. Five animals each received volume replacement therapy with modified fluid gelatin 4% or 8% (MFG4%, MFG8%), 6% HES 200/0.5, or Ringer's solution and were compared to controls receiving 6% HES 200/0.5. Infusion rate was titrated to maintain a central venous pressure of 12 mmHg. Plasma volume was determined using (51)Cr-labelled erythrocytes and standard formulae. Albumin escape rate was calculated using technetium (99m)Tc-labelled albumin. Colloid osmotic pressure, systemic haemodynamics and oxygenation were obtained before and 4 and 8 h after induction of sepsis. Plasma volume was reduced in the Ringer's solution group (-46%) but was maintained in HES (+/-0%), MFG4% (+4%), MFG8% (+23%) groups. Albumin escape rate increased in HES (+52%), MFG4% (+47%), MFG8% (+54%) and the Ringer's solution group (+41%) compared to controls. CONCLUSION: In this porcine septic shock model with concomitant capillary leakage syndrome, confirmed by an increased albumin escape rate, the artificial colloids HES, MFG4%, and MFG8% maintained plasma volume and colloid osmotic pressure. These results suggest the intravascular persistency of artificial colloids in the presence of albumin leakage. An editorial regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-002-1283-9)

Albumins↗

Effects of C1 inhibitor and r-SP-C surfactant on oxygenation and histology in rats with lavage-induced acute lung injury.

OBJECTIVE: To assess the effects of C1 inhibitor (INH) administration and r-SP-C surfactant application on oxygenation and lung histology in an acute respiratory distress syndrome model. DESIGN AND SETTING: Randomized, controlled experimental study in an animal research laboratory. MATERIAL: 36 adult male Sprague-Dawley rats. INTERVENTIONS: Animals were subjected to repetitive lung lavage. Four experimental groups and two control groups were studied: groups 1 and 2 served as controls. Animals of groups 3-6 received 200 U/kg body weight C1-INH (group 3), 25 mg/kg r-SP-C surfactant (group 4) or both (group 5) at 60 min postlavage (pl). Animals of group 6 were treated with 200 U/kg C1-INH1 at 10 min pl. Animals of group 1 were killed 60 min (min) pl, animals of groups 2-6 were killed at 210 min pl. Thereafter the lungs were excised for histological examination. MEASUREMENTS AND RESULTS: Hyaline membrane formation, intra-alveolar neutrophil (PMN) accumulation and intra-alveolar/perivascular haemorrhage were graded semiquantitatively (0-4). Blood gases were determined 120, 150, 180 and 210 min pl. At 210 min pl pO(2) in group 4 (456+/-74 mmHg) and group 5 (387+/-155 mmHg) was significantly higher than in controls (72+/-29 mmHg) or after C1-INH monotherapy (group 3: 120+/-103, group 6: 63+/-12 mmHg). PMN infiltration after C1-INH monotherapy was significantly less severe than in controls. The combination of r-SP-C surfactant and C1-INH led to significantly lower PMN infiltration than surfactant monotherapy. CONCLUSION: In this lavage-induced acute respiratory distress syndrome model the administration of C1-INH might be followed by a higher clinical efficacy of exogenously supplied recombinant SP-C surfactant.

Animals↗

Raman spectroscopic surface characterization of cellulose derivatives.

First results of experiments on the surface characterization of cellulose derivatives are presented. Different water contents of the surface of microcrystalline cellulose have been investigated by means of Raman spectroscopy, SERS, and environmental scanning electron microscopy (ESEM).

Journal Article↗

A plasma membrane-bound enzyme of tobacco roots catalyses the formation of nitric oxide from nitrite.

Purified plasma membranes (PMs) of tobacco (Nicotiana tabacum L. cv. Samsun) roots exhibited a nitrite-reducing enzyme activity that resulted in nitric oxide (NO) formation. This enzyme activity was not detected in soluble protein fractions or in PM vesicles of leaves. At the pH optimum of pH 6.0, nitrite was reduced to NO with reduced cytochrome c as electron donor at a rate comparable to the nitrate-reducing activity of root-specific succinate-dependent PM-bound nitrate reductase (PM-NR). The hitherto unknown PM-bound nitrite: NO-reductase (NI-NOR) was insensitive to cyanide and anti-NR IgG and thereby proven to be different from PM-NR. Furthermore, PM-NR and NI-NOR were separated by gel-filtration chromatography and apparent molecular masses of 310 kDa for NI-NOR and 200 kDa for PM-NR were estimated. The PM-associated NI-NOR may reduce the apoplastic nitrite produced by PM-NR in vivo and may play a role in nitrate signalling via NO formation.

Catalysis↗

Effects of different preparations of propofol, diazepam, and etomidate on human neutrophils in vitro.

BACKGROUND: Intravenous anaesthetics and sedatives can influence polymorphonuclear cell (PMN) functions. Some of the drugs for sedation and anaesthesia have been alternatively dissolved in lipid solutions containing medium (MCT) and/or long chain (LCT) triglycerides. The in vitro effects of two different diazepam (benzyl-alcohol, LCT/MCT), etomidate (propylene-glycol, LCT/MCT), and propofol (LCT, LCT/MCT) preparations on respiratory burst (RB) and phagocytosis of human PMNs were studied. METHODS: Diazepam (2, 20 microg ml(-1)), etomidate (0.5, 5 microg ml(-1)), and propofol (6, 60 microg ml(-1)) were investigated in clinical and 10-fold concentrations with flow cytometric assays. The RB was measured with the fluorescent dye rhodamine after induction with Escherichia coli or formyl-methionyl-leucylphenylalanine (FMLP) following priming with tumour necrosis factor alpha (TNF-alpha). Phagocytosis of PMNs was carried out in whole blood after incubation with fluorescein-labelled E. coli. RESULTS: LCT-propofol at 60 microg ml(-1) reduced the percentage of PMNs with RB activity after induction with E. coli (52.8+/-20.4) and TNF-alpha/FMLP (10.8+/-5.1)) as well as the percentage of phagocytosing PMNs (48.9+/-19.5) in contrast to LCT/MCT-propofol, which augmented all parameters (85.4+/-10.1, 50.3+/-12.7, 66.5+/-12.5). Also the higher concentrations of LCT/MCT-diluted etomidate and diazepam increased the percentage of RB positive PMNs compared to the alternative compositions. The percentage of phagocytosing PMNs was less reduced with 20 microg ml(-1) LCT/MCT-diazepam (85.2+/-6.9) than with the same concentration of benzyl-alcohol diluted diazepam (68.8+/-12.2) compared to the control. CONCLUSION: The in vitro effects of diazepam, etomidate, and propofol are dependent on the solvent applied. The tested LCT/MCT preparations reduce the inhibitory effects on the bacterial killing capacity of PMNs found after incubation with propyleneglycol, benzyl-alcohol, or LCT preparations, respectively.

Anesthetics, Intravenous↗

[Definition of shock types].

Definitions of shock types. Hypovolaemic shock is a state of insufficient perfusion of vital organs with consecutive imbalance of oxygen supply and demand due to an intravascular volume deficiency with critically impaired cardiac preload. Subtypes are haemorrhagic shock, hypovolaemic shock in the narrow sense, traumatic-haemorrhagic shock and traumatic-hypovolaemic shock. Cardiac shock is caused by a primary critical cardiac pump failure with consecutive inadequate oxygen supply of the organism. Anaphylactic shock is an acute failure of blood volume distribution (distributive shock) and caused by IgE-dependent, type-I-allergic, classical hypersensibility, or a physically, chemically, or osmotically induced IgE-independent anaphylactoid hypersensibility. The septic shock is a sepsis-induced distribution failure of the circulating blood volume in the sense of a distributive shock. The neurogenic shock is a distributive shock induced by generalized and extensive vasodilatation with consecutive hypovolaemia due to an imbalance of sympathetic and parasympathetic regulation of vascular smooth muscles.

Anaphylaxis↗

Gastrointestinal manifestations of primary immunodeficiencies.

Congenital immunodeficiencies are relatively rare disorders that result in a marked predisposition to infection and to a variety of gastrointestinal problems. Increasingly recognized in both children and adults, accumulating worldwide experience with these disorders reveals that the long-term prognosis is poor in many cases, despite available treatments. This review highlights the past year's advances concerning the molecular basis of several of these disorders, new diagnostic considerations, and novel therapeutic approaches concerning their gastrointestinal complications. The availability of molecular diagnostic tools increases the options for earlier definitive treatments such as bone marrow transplantation and somatic gene therapy.

Journal Article↗

[Noise in animal housing--a review with special reference to pig housing].

The interpretation of research on noise assessment in animal housing is difficult as goals and methodology of assessment differ substantially between studies. Besides the differences in housing conditions and technology used for measuring noise, a lack of knowledge exists for intra- and interspecies communication, hearing ability and assessment of detrimental consequences following noise exposure. Due to the development of intensive production systems, pigs in all stages of housing are exposed to monotonous chronic noise as well as to a variety of intense noise events. The intention of this review is to document and compare the results of previous studies on noise assessment, in particular housing situations and to demonstrate the impact and significance of the noise problem for farm animal welfare, housing, design and management.

Animal Husbandry↗

Acute animal studies of the STARFlex system: a new self-centering cardioSEAL septal occluder.

The STARFlex system is a modified CardioSEAL device with a flexible self-centering mechanism comprised of nitinol springs strung between opposing arms, a connecting ball (sleeve joint that allows the device to pivot prerelease), and a front-loading delivery system. It was designed to allow a smaller device/defect sizing ratio and delivery profile, provide centering capability, and improve closure rates. To test this system, 13 devices (23, 28, and 33 mm) were deployed in six sheep within created atrial septal defects (12- to 22-mm diameter; n = 10), in the left atrium (n = 2), and in inferior vena cava (n = 1). All implantations in atrial septal defects were successful, with device/defect ratio ranging from 1.3 to 1.9 (median, 1.3), with no residual leak by angiography or echocardiography in seven (3/10 had </= small immediate leaks). The STARFlex system was effective in closing created atrial septal defects using a 10 Fr delivery sheath and low device/defect sizing ratios, comparing favorably with the standard CardioSEAL. Cathet. Cardiovasc. Intervent. 49:225-233, 2000.

Animals↗

Evaluation of noninvasive determinants for capillary leakage syndrome in septic shock patients.

OBJECTIVE: Capillary leakage syndrome (CLS) is a frequent complication in sepsis, characterized by loss of intravasal fluids leading to generalized edema and hemodynamic instability despite massive fluid therapy. In spite of its importance no standardized diagnostic criteria are available for CLS. DESIGN: Prospective clinical study. SETTING: 1,800-bed university hospital PATIENTS: Six septic shock patients with CLS were compared to six control patients. MEASUREMENTS AND RESULTS: CLS was clinically determined by generalized edema, positive fluid balance, and weight gain. Plasma volume was measured by indocyanine green, red blood cell volume by chromium-51 labeled erythrocytes, and colloid osmotic pressure before and 90 min after the administration of 300 ml 20% albumin. Extracellular water (ECW) was measured using the inulin distribution volume and bioelectrical impedance analysis. Red blood cells averaged 20.2 +/- 1.0 ml/ kg body weight in CLS patients and 23.3 +/- 4.1 in controls. ECW was higher in CLS patients than in controls (40.0 +/- 6.9 vs. 21.7 +/- 3.71; p< 0.05). ECW of inulin was correlated with that measured by bioelectrical impedance analysis (r = 0.74, p< 0.01). The increase in colloid osmotic pressure over the 90 min was less in CLS patients than in controls (1.1 +/- 0.3 vs. 2.8 +/- 1.3 mmHg;p< 0.05). CONCLUSION: These results suggest that measurements of an increased ECW using bioelectrical impedance analysis combined with a different response of colloid osmotic pressure to administration of albumin can discriminate noninvasively between patients with and those without CLS.

Adult↗

Colchicine-induced bone marrow suppression: treatment with granulocyte colony-stimulating factor.

Bone marrow aplasia is a frequent complication of colchicine poisoning. This typically occurs on day 3 to 5 postexposure, and the blood cell counts remain depressed for a week or more. Unfortunately, because patients suffering from colchicine toxicity develop multiple organ complications and sepsis, the morbidity and mortality associated with bone marrow depression is high. In this article, we present three cases of colchicine toxicity in which granulocyte colony-stimulating factor (G-CSF) was used to treat bone marrow depression. In all three cases, there was a dramatic increase in the white cell count and, to a lesser extent, the platelet count. In view of the critical nature of the bone marrow depression and multi-organ toxicity induced by colchicine, we believe that consideration of the use of G-CSF to shorten the duration of neutropenia is warranted.

Adolescent↗

Low-dose dopexamine in patients undergoing hemihepatectomy: an evaluation of effects on reduction of hepatic dysfunction and ischaemic liver injury.

BACKGROUND: Hepatic dysfunction is a common problem in patients after hemihepatectomy. Treatment with low-dose dopamine has been shown to be beneficial in hemihepatectomy patients. We hypothesized that dopexamine, a synthetic vasoactive catecholamine, due to its specific pharmocodynamic profile may be more effective in reducing hidden ischaemic episodes in the hepato-splanchnic region during and after temporary total cross-clamping of hepatic inflow in these patients. METHODS: The effects of low-dose dopexamine on hepatic venous haemoglobin oxygen saturation (ShvO2), hepatic venous lactate level, monoethylglycinxylid (MEGX) formation, hepatic synthetic function and indicators for hepatic cell damage were studied during hemihepatectomy and for 16 h postoperatively in hemihepatectomy patients and compared to those of low-dose dopamine. In a prospective, double-blind clinical study 20 patients received randomly either dopexamine (DPX) 0.5 microg kg(-1) min(-1) (n=10) or dopamine (DO) 2.5 microg kg(-1) min(-1) (n= 10). Infusions were started after induction of anaesthesia and continued 16 h postoperatively. Hepatic vein, radial and pulmonary artery were catheterized. Measurements were carried out after induction of anaesthesia, after total cross-clamping of hepatic inflow, and at 2 h and 16 h postoperatively. RESULTS: There were no differences in systemic haemodynamics, oxygenation, ShvO2, serum aminotransferases or MEGX levels between the groups. At 16 h postoperatively prothrombin and antithrombin III levels were significantly lower while hepatic venous lactate was significantly higher in the DPX group compared to the DO group. CONCLUSION: In patients undergoing hemihepatectomy, we could not reveal superior hepatoprotective effects of low-dose dopexamine compared to low-dose dopamine.

Adult↗

Protective effects of plasma replacement fluids on erythrocytes exposed to mechanical stress.

Haemoglobin release from 40 suspensions of packed red blood cells in modified fluid gelatin, 4% albumin solution, 6% hydroxyethyl starch and normal saline was investigated in vitro during circulation with a roller pump from a heart-lung machine for 120 min at a flow rate of 2.5 l.min-1 at room temperature. The lowest haemoglobin release was obtained with erythrocytes in modified fluid gelatin, whereas free haemoglobin concentrations became progressively higher with albumin, hydroxyethyl starch and normal saline [median free haemoglobin (interquartile range) after 120 min circulation: gelatin 493 (360-601) mg.l-1, albumin 692 (590-1111) mg.l-1, hydroxyethyl starch 1121 (692-1518) mg.l-1, normal saline 1178 (881-1757) mg.l-1, p < 0.001]. Modified fluid gelatin appears to have potent erythrocyte protective properties similar to those of albumin. This effect could decrease mechanical haemolysis during extracorporeal circulation or cell saver autotransfusion if modified fluid gelatin is used as part of a priming solution or as an additive in wash solutions.

Erythrocytes↗