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Biomedical subjects

C Lehmann

Publications and source records attributed to C Lehmann.

At least 55 records · Page 3Linked to original sources
PubMed1998

Parenteral selenium supplementation in critically ill patients--effects on antioxidant metabolism.

Decreased plasma selenium (Se) levels are common in critically ill patients. Oxidative stress is regarded as one possible cause of the Se deficiency. We investigated in 20 critically ill patients with decreased plasma selenium concentrations the antioxidant metabolism during parenteral selenium supplementation (week 1: 2 x 500 micrograms; week 2:1 x 500 micrograms, week 3:3 x 100 micrograms sodium selenite). As marker of oxidative stress we measured the plasma malondialdehyde levels on days 0, 1, 3, 7, 14, and 21. The content of reduced and oxidized glutathione as well as the leucocyte activity marker elastase were estimated on the same days. Initial plasma Se levels were considerably decreased (0.44 +/- 0.1 mumol/l, mean +/- SEM). After one day of supplementation Se concentrations were in the reference range. Plasma malondialdehyde levels and the ratio of oxidized and reduced glutathione were initially elevated and decreased beginning on day 3 of supplementation. The mean elastase level was 113 +/- 10 micrograms/l on day 0. On day 3 elastase values decreased significantly (85 +/- 13 micrograms/l, p < 0.05; day 21, 19 +/- 7 micrograms/l, p < 0.001). Antioxidant metabolism showed significant changes beginning after 72 hours of therapy. This latency may be explained with the induction of the enzyme glutathione peroxidase. The lowered plasma Se concentrations measured in the critically ill patients and the significant effects on antioxidant metabolism during supplementation emphasized the importance of selenium administration in these patients.

Adult↗
PubMed1997

[Effect of selenium administration on various laboratory parameters of patients at risk for sepsis syndrome].

BACKGROUND: Low selenium plasma levels were often measured in ICU patients with polytrauma, major surgery or various severe diseases. Activation of selenium-dependent functions of the antioxidant metabolism and the immune system is suggested to be causally. METHODS: In a prospective randomized clinical trial including 24 critically ill patients we investigated the plasma levels of selenium, malondialdehyde, glutathione, elastase, fT3, fT4, TSH, IL-2R, IL-6 and IL-8 with and without parenteral selenium supplementation for 3 weeks (study design: week 1: twice 500 micrograms daily, week 2: once 500 micrograms, week 3: three times 100 micrograms sodium selenite). RESULTS: Following 24 hours of supplementation selenium plasma levels were normalized. Malondialdehyde level decreased in the therapy group significantly beginning at day 3. In the control group we observed increased malondialdehyde values, a disturbed glutathione metabolism and an elevated elastase activity. fT3-values were diminished at day 0 in all patients. In the therapy group we measured a gradual fT3 restoration. In the control group a reactive TSH increase was observed. Selenium supplementation did not lead to an excessive stimulation of IL-2R, IL-6 or IL-8. CONCLUSIONS: 1. Rapid normalization of selenium plasma levels can be achieved with the applied selenium dosage. 2. Parameters of radical metabolism are significantly reduced following selenium administration. 3. T3 synthesis correlates closely with the selenium levels. 4. Excessive stimulation of the immune system does not appear in the applied dosage.

Adult↗
PubMed1997

Hypoxia-ischemia causes abnormalities in glutamate transporters and death of astroglia and neurons in newborn striatum.

The neonatal striatum degenerates after hypoxia-ischemia (H-I). We tested the hypothesis that damage to astrocytes and loss of glutamate transporters accompany striatal neurodegeneration after H-I. Newborn piglets were subjected to 30 minutes of hypoxia (arterial O2 saturation, 30%) and then 7 minutes of airway occlusion (O2 saturation, 5%), producing cardiac arrest, followed by cardiopulmonary resuscitation. Piglets recovered for 24, 48, or 96 hours. At 24 hours, 66% of putaminal neurons were injured, without differing significantly thereafter, but neuronal densities were reduced progressively (21-44%). By DNA nick-end labeling, the number of dying putaminal cells per square millimeter was increased maximally at 24 to 48 hours. Glial fibrillary acidic protein-positive cell body densities were reduced 48 to 55% at 24 to 48 hours but then recovered by 96 hours. Early postischemia, subsets of astrocytes had fragmented DNA; later postischemia, subsets of astrocytes proliferated. By immunocytochemistry, glutamate transporter 1 (GLT1) was lost after ischemia in the astroglial compartment but gained in cells appearing as neurons, whereas neuronal excitatory amino acid carrier 1 (EAAC1) dissipated. By immunoblotting, GLT1 and EAAC1 levels were 85% and 45% of control, respectively, at 24 hours of recovery. Thus, astroglial and neuronal injury occurs rapidly in H-I newborn striatum, with early gliodegeneration and glutamate transporter abnormalities possibly contributing to neurodegeneration.

ATP-Binding Cassette Transporters↗
PubMed1997

Orthotopic liver transplantation with preservation of portocaval flow compared with venovenous bypass.

Conventional liver transplantation requires cross-clamping of the hepatic pedicle and inferior vena cava, leading to severe hemodynamic and metabolic disturbances, usually attenuated by the use of venovenous bypass. A more recent surgical technique, piggyback with temporary portocaval shunting, preserves both caval and portal blood flows. The aim of this study was to compare the two methods prospectively. Forty-four patients with chronic liver disease were studied. Local anatomic conditions guided the surgeon to choose the easiest way to remove the native liver. Anesthetic management was standardized. Hemodynamic and metabolic changes were assessed by use of routine tests at specific periods. Graft function was evaluated by measurement of aminotransferases and monoethylglycinexylidide (MEGX) test 12, 24, 48, and 72 hours postoperatively. Conventional liver transplantation with venovenous bypass was performed in 26 patients, and the piggyback with temporary portocaval shunting was performed in 15 patients. ANOVA showed that cardiac output and systemic oxygen delivery were better maintained before revascularization in the piggyback group. Metabolic changes were comparable, and hyperfibrinolytic activity was detected in both groups. Graft function was comparable and satisfactory within the 3 first postoperative days. Piggyback with temporary portocaval shunting provided better intraoperative hemodynamics and tissue oxygenation than liver transplantation with venovenous bypass.

Adult↗
PubMed1997

Effects of cell surface ganglioside sialidase inhibition on growth control and differentiation of human neuroblastoma cells.

Gangliosides on the external side of the plasma membrane are important modulators of cellular functions. In previous work we had found that in cultured human SK-N-MC neuroblastoma cells a cell surface sialidase activity specifically cleaved terminal sialic acids from gangliosides, leading to a shift from higher sialylated species to GM1 and a decrease of GM3. To further elucidate the function of the enzyme, we have now examined the consequences of ganglioside sialidase inhibition. When present in the culture medium, the ganglioside sialidase inhibitors 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (NeuAc2en), heparin, and heparan sulfate caused dramatic changes in cell behavior. Thus, the inhibitors uniformly led to a complete release from contact inhibition of growth, and to the loss of the differentiation markers neuron-specific enolase and neurofilaments, and a decrease of cyclic AMP. In presence of NeuAc2en, cells that normally were spread out evenly and were firmly attached, appeared smaller, rounded, and only loosely adherent to the culture vessel. Exogenous addition of vibrio cholerae sialidase mimicked the action of the plasma membrane ganglioside sialidase by retarding cell proliferation and increasing intracellular acetylcholinesterase. That the ganglioside sialidase inhibitors in the culture medium indeed affected solely the cell surface enzyme and not also a lysosomal sialidase, was demonstrated in an experiment where the desialylation of exogenously added radioactive gangliosides was determined in absence and presence of NeuAc2en and NH4Cl, an inhibitor of lysosomal function. Taken together, our results suggest that the ganglioside sialidase on the surface of SK-N-MC cells is responsible for growth control and differentiation in this neuronal cell line.

Antigens, Differentiation↗
PubMed1996

Inhibition of duck hepatitis B virus replication by 2',3'-dideoxy-3'-fluoroguanosine in vitro and in vivo.

The antiviral activity of 2',3'-dideoxy-3'-fluoroguanosine (FdG) or its triphosphate was evaluated in the duck hepatitis B virus (DHBV) system in vitro and in vivo. In primary DHBV-infected hepatocytes FdG results in a dose-dependent inhibition of viral replication with a nearly complete inhibition at a concentration of 1 microM. Also in vivo, FdG treatment of DHBV-infected ducklings reduces DHBV DNA replication by more than 90%. These data demonstrate that FdG is a strong inhibitor of DHBV replication in vitro and in vivo.

Animals↗
PubMed1996

[Perioperative intra-arterial irrigation perfusion for adjuvant therapy of acute intestinal circulatory disorders].

The extent of mesenteric infarctions caused by intestinal circulation disorders essentially depends on reactive vasoconstriction and oxygen radical induced lesions of enteric mucosa. Animal experiments indicated protective effects of an intraarterial flushing perfusion of mesenteric arteries with vasodilators and anti-oxidants. We carried out a transaortic perfusion of the superior mesenteric artery with lactated Ringer's-solution and vasodilators (papaverin, tolazolin, PGE1) in acute occlusion of mesenteric arteries in 12 patients (case reports). Three patients were treated successfully without reconstruction by conservative method alone. Only one patient (8.33%) died because of uncontrolled enteric ischemia. Angiological therapy is necessary in modern treatment of acute mesenteric ischemia. Surgical goals are elimination of central vascular occlusions and resection of necrobiotic areas of intestinal organs.

Aged↗
PubMed1996

[Pharmacologic modification of intestinal reperfusion injury in the animal experiment].

We evaluated experimentally (80 Lewis-rats) possible pharmacological strategies in the treatment of intestinal reperfusion injury in hypo- and normothermia. We used a specific perfusion solution containing PGI2 or radical scavengers (superoxide dismutase, oxypurinol, tocopherol, ascorbate). Decreased malondialdehyde (MDA) plasma release after reperfusion proved the antioxidative efficiency of the administered radical scavengers (normothermia-control group: MDA increase after 15 min of reperfusion to 160 +/- 30% compared to level at the end of ischemia, oxypurinol: 110 +/- 23%, tocopherol: 112 +/- 12%, ascorbate: 104 +/- 20%; p < 0.05). The ATP/ADP-ratio of the therapy groups was stable in contrast to the control group. Alkaline phosphatase release was significantly diminished under radical scavenger administration (normothermia/15 min reperfusion-control group: 7.7 +/- 0.9 mumol/ls, oxypurinol: 4.4 +/- 0.4 mumol/ls, tocopherol: 3.5 +/- 0.1 mumol/ls, ascorbate: 5.9 +/- 0.3 mumol/ls; p < 0.05). Histologically we observed a mucosa protective effect particularly in the ascorbate group. Other pharmacological strategies are discussed.

Animals↗
PubMed1995

NMR studies of DNA duplexes singly cross-linked by different synthetic linkers.

Molecular modelling studies resulted in the design of a variety of non-nucleotidic covalent linkers to bridge the 3'-end of the (+)-strand and the 5'-end of the (-)-strand in DNA duplexes. Three of these linkers were synthesized and used to prepare singly cross-linked duplexes d(GTGGAATTC)-linker-d(GAATTCCAC). Linker I is an assembly of a propylene-, a phosphate- and a second propylene-group and is thought to mimic the backbone of two nucleotides. Linkers II and III consist of five and six ethyleneglycol units, respectively. The melting temperatures of the cross-linked duplexes are 65 degrees C for I and 73 degrees C for II and III, as compared with 36 degrees C for the corresponding non-linked nonadeoxynucleotide duplex. The three cross-linked duplexes were structurally characterized by nuclear magnetic resonance spectroscopy. The 1H and 31P resonance assignments in the DNA stem were obtained using standard methods. For the resonance assignment of the linker protons, two-dimensional 1H-31P heteronuclear COSY and two-quantum-experiments were used. Distance geometry calculations with NOE-derived distance constraints were performed and the resulting structures were energy-minimized. In duplex I, the nucleotides flanking the propylene-phosphate-propylene-linker do not form a Watson-Crick base pair, whereas in duplexes II and III the entire DNA stem is in a B-type double helix conformation.

Base Sequence↗
PubMed1995

Efficacy and proarrhythmia of oral sotalol in pediatric patients.

OBJECTIVES: This study sought to assess the efficacy of oral sotalol for various arrhythmias in pediatric patients and to evaluate the incidence of proarrhythmia and systemic side effects. BACKGROUND: Sotalol is a beta-adrenergic blocking agent with additional class III antiarrhythmic properties. Experience in pediatric patients is limited. Data concerning the incidence of proarrhythmia in children are lacking. METHODS: Seventy-one pediatric patients (mean age 7.3 years) with various supraventricular and ventricular tachyarrhythmias were treated with oral sotalol. All the patients were admitted to the hospital for initiation of sotalol therapy. Antiarrhythmic and proarrhythmic effects of sotalol were assessed by daily surface electrocardiograms (ECGs) during the in-hospital phase and by serial Holter monitoring. RESULTS: Sotalol was either completely (27 [66%] of 41 patients) or partially effective (11 [27%] of 41) in 38 (93%) of 41 patients with supraventricular reentrant tachycardias. In patients with atrial flutter predominantly after operation for congenital heart disease, sotalol was effective in 84% of patients (completely in 9 of 19 and partially in 7 of 19). Ventricular tachycardia was completely (3 of 11) or partially (4 of 11) controlled in 64% of children. Proarrhythmia occurred in seven patients (10%) and consisted of symptomatic bradycardia from sinoatrial block and high grade atrioventricular (AV) block, respectively, in two children; asymptomatic high grade AV block in one; torsade de pointes in one; and relevant increased ventricular ectopic activity in three. Proarrhythmia required drug discontinuation in four patients. Mean duration of treatment for all patients was 18 months (range 1 to 40). CONCLUSIONS: Sotalol was an effective antiarrhythmic drug for a wide range of pediatric tachyarrhythmias. The considerable number of patients with proarrhythmic effects indicates the need for initiation of treatment on an inpatient basis and close monitoring by serial Holter electrocardiography.

Administration, Oral↗
PubMed1995

Perioperative vascular flushing perfusion in acute mesenteric artery occlusion.

AIM: To evaluate in animals and patients a perioperative vascular flushing perfusion with antioxidants in order to improve postischaemic condition of the bowel and hence, to prolong the warm ischaemia tolerance time. MATERIALS: 40 rats and 10 patients with acute mesenteric artery occlusion. METHODS: Intestinal ischaemia was induced in 40 rats by clipping the superior mesenteric artery for 1 h. Thirty animals received a vascular flushing perfusion with oxygen radical scavengers (ascorbate, tocopherol or oxypurinol). Histology, ATP, ADP levels were examined in tissue biopsies and malondialdehyde, lactate dehydrogenase, alkaline phosphatase levels were measured in blood during ischaemia and 60 min after reperfusion. RESULTS: ATP restoration was particularly improved in the oxypurinol group (ATP/ADP-ratio = 2 vs. 1.2 in the control group). Malondialdehyde increase observed after reperfusion as a marker of radical induced lipid destruction was significantly attenuated (control group 160% of base level vs. 127% in the ascorbate group, 133% in the tocopherol group, 121% in the oxypurinol group). Histological alterations during ischaemia/reperfusion were markedly less extensive in the perfusion groups than in control. The patients treated perioperatively with arterial flushing perfusion had an overall mortality of 10%. CONCLUSION: Vascular flushing perfusion with oxygen radical scavengers prevents radical induced ischaemic damage and may prolong the warm ischaemic tolerance time of the intestine.

Acute Disease↗
PubMed1994

Electrocardiogram acquisition during MR examinations for patient monitoring and sequence triggering.

We have developed a method for measuring the electrocardiogram (ECG) continuously during MR examinations. In contrast to ECG acquisition by wires, our new method is to amplify and convert the ECG into an optical signal directly above the patient's heart. The optical signal is transmitted out of the magnet bore by optical fiber. The small and fixed dimensions of the ECG amplifier avoid interactions with the MR system because of shorter electrical structures and smaller enclosed areas. Tests of the proposed device in a 1.5 Tesla MR system show that continuous and reliable ECG monitoring and sequence triggering are possible.

Adult↗
PubMed1994

[Results of oral sotalol therapy in children with supraventricular and ventricular arrhythmias].

Experience with oral sotalol, a beta-blocker with class III-antiarrhythmic properties, is limited in the pediatric population. Sotalol was administered to 32 patients with a mean age of 8.7 years (range 1 day-19.9 years). Mean dosage was 4.6 (1.5-9.4) mg/kg or 122.1 (52-306) mg/m2, respectively. In 27/32 patients, at least 1 antiarrhythmic agent had failed to control the dysrhythmia before sotalol was started. Cardiac diagnoses included normal heart (n = 16), status after correction of congenital heart disease (n = 13), and cardiomyopathy (n = 3). Success (based on symptoms and 24-h electrocardiogram) was achieved in 16/18 patients with reentry supraventricular tachycardia, in 7/8 patients with atrial flutter, and in 4/6 patients with ventricular tachycardia. During a mean follow-up of 15.6 (2-78) months, proarrhythmia occurred in five (16%) patients (symptomatic bradycardia n = 2, QT-prolongation and ventricular extrasystoles n = 1, ventricular extrasystoles n = 1, 2 degrees av-block n = 1), requiring dosage reduction (n = 3), cessation of treatment (n = 1) and pacemaker implantation in one patient, respectively. Symptomatic hypotension was noted in two patients, in whom therapy had to be stopped. Sotalol was a very effective agent for the treatment of various pediatric cardiac dysrhythmias. However, incidence of proarrhythmic effects warrants close electrocardiographic monitoring.

Administration, Oral↗
PubMed1993

Transesophageal echocardiography for prosthetic valve evaluation: is it always necessary?

Transesophageal echocardiography provides excellent images of mitral and aortic prostheses, due to its higher resolution and less interference from other cardiac structures. Since the introduction of transesophageal echocardiography, it has proved to be valuable for the evaluation of prosthetic heart valves. "Classic" indications include the evaluation of prosthetic valve endocarditis, the search for paravalvular abscesses, and the assessment of regurgitation in mechanical, especially mitral, prostheses. New technical developments such as biplane or multiplane transducers enhance the diagnostic capabilities of the technique. Transesophageal echocardiography can also have advantages in recognizing obstructive lesions such as thrombi or pannus, and help understand the complex morphology of prostheses in grafts. Transesophageal echocardiography should be considered a backup technique whenever transthoracic echocardiography, which always remains the primary approach, is inconclusive or negative in the presence of clinically suspected prosthetic valve malfunction.

Aortic Valve↗
PubMed1991

Sensibility and cutaneous reinnervation after breast reconstruction with musculocutaneous flaps.

Sensibility and sensory reinnervation were investigated in 19 patients who underwent, after mastectomy, a breast reconstruction using myocutaneous flaps. A comparative study in reinnervation of the flaps has been performed either after surgery with a latissimus dorsi flap with prosthesis or after surgery with a simple or double pedicle transverse rectus abdominal flap. Ten patients with latissimus dorsi flaps and 9 patients with transverse rectus abdominal flaps were tested. The tests included stimulation with touch, pressure, pin prick, and temperature. The patients were also interviewed regarding their impressions, a subjective sensibility. These results show that the recovery of sensibility by patients who underwent surgery with the transverse rectus abdominal flap technique is superior, objectively and subjectively.

Adult↗