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Biomedical subjects

J Vogt

Publications and source records attributed to J Vogt.

At least 73 records · Page 4Linked to original sources
PubMed1998

Simultaneous determination of plasma enrichments of 1-13C- and 15N-labelled phenylalanine and tyrosine.

A methylchloroformate derivative was used for the simultaneous determination of plasma enrichments of 1-13C-phenylalanine, 1-13C-tyrosine, 15N-phenylalanine and 15N-tyrosine by gas chromatography/mass spectrometry. All four tracer enrichments could be measured in a single GC run. A specific ion fragment was obtained for each tracer. This approach allowed an easy determination of the "tracer to tracee ratios". Each ion fragment could be measured with an appropriate single-to-noise ratio and precision in samples obtained from 100 microliters plasma. The derivatization consists of a fast one-step reaction. Therefore it is well suited for studies involving a large number of samples, such as non-steady state bolus studies.

Carbon Isotopes↗
PubMed1998

Oxygen permeability of a new type of high Dk soft contact lens material.

Lotrafilcon A is a biphasic block-copolymer, comprising a highly permeable siloxane-based polymeric phase, coupled with a water phase (hydrogel phase). The high oxygen permeability of this material, and the fact that it is a hydrogel, places it outside the applicability of both the polarographic ISO standard and coulometric ISO draft standards for contact lens Dk determination. The oxygen permeability (Dk) and transmissibility (Dk/t) of lotrafilcon A lenses were determined by an adaptation of the standard coulometric method. Lenses with a thickness (t) range from 30 microns to over 300 microns were measured in a liquid-to-gas and a gas-to-gas configuration in an effort to combine features of the ISO (draft) standards to yield a valid measurement of the intrinsic material's oxygen transmission characteristics. The following results, for lotrafilcon A, are the mean values and SE for the oxygen permeability coefficient (Dk) determined at 34 degrees C: 140 +/- 2 barrer with water overlay (liquid-to-gas) at 2100 rpm stirring speed, 150 +/- 5 barrer with water overlay (liquid-to-gas) at "infinite" stirring speed, and 170 +/- 2 barrer without water overlay (gas-to-gas), where barrer = 10(-11) (mlO2.cm)/(sec.cm2.mm Hg). Clinical lenses produced from this material are expected to be in the 60 to 90 microns thickness range, with an average center thickness of 80 microns. Given that the Dkmaterial is greater than or equal to 140 barrers, for this material, a parallel sided lens of 80 microns central thickness would exhibit a lens transmissibility (Dk/t) of at least 170 x 10(-9) mlO2/(sec.cm2.mm Hg) at 34 degrees C. This transmissibility is well in excess of the 87 x 10(-9) mlO2/(sec.cm2.mm Hg) value postulated to be sufficient to prevent overnight lens-induced corneal swelling and places it in the hyper-permeable material category.

Contact Lenses, Hydrophilic↗
PubMed1998

Percutaneous closure of secundum atrial septal defect with a new self centering device ("angel wings").

OBJECTIVE: To investigate the safety, efficacy, and clinical application of a new self centering device ("angel wings") for closure of secundum atrial septal defects (ASD II) and persistent foramen ovale in all age groups. DESIGN: Multicentre, prospective, nonrandomised study. PATIENTS INCLUSION CRITERIA: defects with an occlusive diameter of < or = 20 mm and a surrounding rim of > 4 mm; body weight > 10 kg; and an indication for surgical closure of secundum atrial septal defect. Additionally, there were compassionate indications for closure in patients with persistent foramen ovale. INTERVENTIONS: Defects were closed by a transcatheter device consisting of two square frames made of superelastic nitinol wire. The frames are covered by elastic polyester fabric, which is sewn together at a central circle. All procedures, except for three interventions that were carried out under sedation, were performed under general anaesthesia using transoesophageal echocardiography and fluoroscopy to monitor intervention. RESULTS: Closure was attempted in 75 (71%) of 105 patients. An ASD II was present in 35 children and 15 adults. A persistent foramen ovale was present in 25 adults with suspected paradoxical embolism. Transcatheter closure was unsuccessful in three children and crossover to surgery was required. Residual shunts were found in 20 patients (27%) immediately after the procedure. A transient atrioventricular third degree block occurred in three patients (4%) and the right atrial disk was not fully deployed in three. A minor shunt (< 3 mm) was present in only three (4%) of 72 patients during follow up of 1-17 months. Blood clots on the right atrial disks in two patients (one required lysis) were seen during follow up transoesophageal echocardiography. Serious complications demanding surgical removal of the device occurred in three patients. One patient had haemopericardial tamponade because of an aortic lesion. Left atrial thrombus formation due to an unfolded right atrial disk was found in a second patient and dislodgement of the left atrial disk resulted in a large residual shunt in a third. CONCLUSIONS: Percutaneous closure of a central ASD with a diameter < or = 20 mm in paediatric and adult patients is feasible and effective with this new device. It is a promising alternative to surgical closure. Modifications of the design, however, seem to be mandatory as 4% of patients developed serious complications.

Adolescent↗
PubMed1998

Reduced expression of plakoglobin indicates an unfavorable prognosis in subsets of patients with non-small-cell lung cancer.

PURPOSE: Plakoglobin is thought to play a key role in cadherin-mediated epithelial cell adhesion, because it is a common component of desmosomal and nondesmosomal adherens junctions. Because loss of homotypic cell adhesion is an important early step in invasion and metastasis of solid tumors, we evaluated the frequency and prognostic significance of a deficient expression of plakoglobin in human lung cancer. PATIENTS AND METHODS: At primary surgery, representative specimens of the primary tumor were obtained from 96 consecutive patients with completely resected non-small-cell lung carcinoma (NSCLC) without overt distant metastases. Cryostat sections of these specimens and metastatic lymph nodes were stained with monoclonal antibody (mAb) PG 5.1 against plakoglobin, using an immunoperoxidase technique. Patients were monitored for a median of 39 months (range, 12 to 56) after surgery. RESULTS: Absent or severely reduced expression of plakoglobin (ie, < 30% positive tumor cells) was observed in 39 patients (40.6%). There was no significant correlation to established risk factors, such as the histology, extension, and histologic grade of the primary tumor and metastatic lymph node involvement, or expression of alpha-catenin. Expression of plakoglobin in lymph node metastases ranged from 0% to greater than 60% positive tumor cells. Deficient plakoglobin expression on the primary tumor was significantly correlated to a shortened disease-free and overall survival in patients with adenocarcinomas, pT1-2 tumors, or negative lymph nodes (pN0). In patients with pT1-2 tumors, the independence of this prognostic influence from established risk factors was demonstrated by Cox regression analyses (disease-free survival, P = .002; overall survival, P = .038). CONCLUSION: Deficient expression of plakoglobin appears to be an important event in the progression of NSCLC.

Adult↗
PubMed1998

Determination of 13CO2/12CO2 ratio by IRMS and NDIRS.

Breath tests using 13C-labelled substrates require the measurement of 13CO2/12CO2 ratio in breath gas samples. Next to isotope ratio mass spectrometry (IRMS), which is very sensitive but also complex and expensive, alternatively isotope selective nondispersive infrared spectrometry (NDIRS) can be used to determine the 13CO2/12CO2 ratio in expired breath. In this study we compared NDIRS- with IRMS-results to investigate whether the less expensive and very simply to operate NDIRS works as reliable as IRMS. For this purpose we applicated 1- 13C-Phenylalanine to patients with advanced liver cirrhosis and healthy volunteers and took duplicated breath samples for IRMS and NDIRS at selected time points. Our data show a good correlation between these two methods for a small number of samples as required for simple breath tests. Longer series, where repeated measurements are required on the NDIRS instrument lead to a decreasing correlation. This indicates the superiority of IRMS concerning 13CO2-kinetics over longer time periods.

Breath Tests↗
PubMed1998

Clinical symptom presentation in suspected malingerers: an empirical investigation.

To empirically investigate the usefulness and validity of clinical presentation and recent history variables in the detection of malingered psychiatric disorder, 30 criminal defendants involved in forensic evaluations, who had a documented history of psychiatric hospitalization preceding their arrest on the instant offense (low risk of malingering group) and 30 defendants who complained of psychiatric difficulties but had no history of psychiatric hospitalization or treatment (suspected malingering group) were studied. Each subject's mental status was rated, blind to psychiatric history, diagnosis, and psycholegal opinions, on a Likert-like scale for the uncommon nature of their symptom presentation. In addition, the final outcome of the court cases, whether they were found competent to stand trial, not guilty by reason of insanity, or evidenced diminished capacity was determined by obtaining the court disposition in each case. Based on the unusual nature of their presentation, the defendants suspected of malingering were discriminated from the low risk of malingering defendants with a 90 percent rate of correct classification. Suspected malingerers were found to evidence current psychiatric presentations inconsistent with their recent Global Assessment of Functioning, unusual symptom presentation, and hallucinatory experiences rated as atypical for psychiatric disorder. A high proportion of suspected malingerers were found competent to proceed. The results are discussed in terms of the usefulness of clinical identification of malingering.

Adult↗
PubMed1998

[Hemodynamic changes and nitric oxide production in an experimental model of sepsis].

Nitric [correction of Nitrous] oxide is most likely a queer "end mediator" giving rise to vasoplegia in septic shock patients. The study is aimed at comparative assessment of kinetic changes in the synthesis of nitric [correction of nitrous] oxide in experimentally induced sepsis model with the corresponding hemodynamic parameters. The laboratory animals--pigs--are divided up in two groups, and exposed to general narcosis induction, orotracheal intubation and mechanical ventilation under controlled regimen. The hemodynamic parameters studied include: MAP, CO and SVR. Additional endotoxin (1 mg/50 ml) in the form of infusion is given to the animals in the sepsis group. Nitrate production mirrors NO synthesis, insofar as there are no other relevant mechanisms of nitrate synthesis. The kinetic parameters of nitrate production are estimated using stable nitrate isotopes--N15. The theory of compartment models and appropriate computerized simulation are used to calculate the respective constants. In the endotoxin treated group (n = 5) a significantly higher level of synthesis of induced NO production is documented--26 +/- 9 mumol/h, as compared to production in the control group--6 +/- 7 mumol/h, as well as a significant increase in cardiac output and systemic vascular resistance reduction. The good correlation between enhanced NO production and hemodynamic response (increase in cardiac output and decrease in systemic vascular resistance) corroborates the validity of the method.

Animals↗
PubMed1997

Gluconeogenesis in patients with impaired liver function.

This presentation gives an overview about the factors involved in the regulation of gluconeogenesis. Then, based on these regulatory principles, the changes seen in impaired liver function are discussed. Gluconeogenesis from lactate and pyruvate is mediated through pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK) activity. The PC mediated pathway depends on substrate supply and on the downregulation of the oxidative pathway for pyruvate. Both enzymes need ATP or GTP and, thus, depend on the cellular energy charge. Tissue anoxia can reduce the energy charge and limit the flow through the PEPCK pathway. Thus, one expects a coupling between reduced splanchnic blood flow, limited oxygen supply to the liver, resulting tissue anoxia, and reduced gluconeogenesis. Conditions are shown, where this coupling exists. Since gluconeogenesis is concentrated in the periportal region of the liver, the local oxygen tension is sufficient under many circumstances to maintain a high glucose production level. Also, the enzyme activity of PEPCK can compensate for long term anoxia. Thus, gluconeogenesis is sufficient in most cases, as seen in critically ill patients. However, this could be associated with a reduction in the perivenous oxygen tension, possibly below critical levels. Beta-adrenergic stimulation increases gluconeogenesis. Examples are shown where this stimulation can overlay the dependency on the oxygen tension and substrate supply. Catecholamines are generally used to stabilize the hemodynamic system. This treatment could limit splanchnic bloodflow and, as a consequence, the oxygen supply to the liver with a simultaneous stimulation of gluconeogenesis and can cause severe anoxia in the perivenous region. These negative side effects of catecholamine treatment should be avoided and the ideal treatment should aim at improving splanchnic flow without stimulation of gluconeogenesis.

Gluconeogenesis↗
PubMed1997

Availability of stable isotope tracers for human use.

Stable isotope tracers do not have approval for diagnostic use in humans. We assume that stable isotope tracers behave like natural compounds, because there is no evidence for the opposite despite a wide use in human studies. From this point of view, they are drugs comparable to unlabelled natural substances. Under this assumption a pharmacy is allowed to prepare isotope solutions by following the guideline for the preparation of infusion solutions using chemicals. The pharmacy has to perform tests for identification, content and purity following the U.S. pharmacopoeia or the corresponding national standard for the unlabelled drug. If these tests are passed then it can prepare the tracer solution. An approach is outlined which is designed to ensure sterility of the preparation as far as possible and an adequate pharmaceutical quality. From the regulation for the preparation we define requirements for an alternative preparation for immediate infusion by the physician.

Humans↗
PubMed1997

[Value of intravascular ultrasound in angiographically underestimated coronary findings: exemplified by 2 case reports].

Coronary angiography is considered to be the most important component in the diagnosis of coronary artery disease. Only the lumen may be visualized using contrast radiography of the coronary arteries, however. With intravascular ultrasound, on the other hand, pathological changes in the vascular wall can be recorded. Despite typical symptoms, an angiographical image of the coronary arteries is sometimes unable to show unambiguous stenotic lesions of the coronary arteries. In such cases, intravascular ultrasound provides a new complementary diagnostic tool for detecting even early forms of arteriosclerosis or angiographically underestimated coronary findings. Two cases are used to illustrate this. In those, angiographic visualization of the coronary arteries was unable to produce an unambiguous finding despite typical clinical symptoms, yet intravascular ultrasound could detect considerable arteriosclerotic wall changes.

Coronary Artery Disease↗
PubMed1997

[3-13C] gamma-linolenic acid: a new probe for 13C nuclear magnetic resonance studies of arachidonic acid synthesis in the suckling rat.

Our objective was to develop a suitable probe to study metabolism of polyunsaturated fatty acids by 13C nuclear magnetic resonance (NMR) in the suckling rat pup. [3-13C] gamma-Linolenic acid was chemically synthesized, and a 20 mg (Experiment 1) or 5 mg (Experiment 2) dose was injected into the stomachs of 6-10-day-old suckling rat pups that were then killed over a 192 h (8 d) time course. 13C NMR showed that 13C in gamma-linolenate peaked in liver total lipids by 12-h post-dosing and that [5-13C]-arachidonic acid peaked in both brain and liver total lipids 48-96 h post-dosing. 13C enrichment in brain gamma-linolenic acid was not detected by NMR, but gas chromatography-combustion-isotope ratio mass spectrometry showed that its mass enrichment in brain phospholipids at 48-96 h post-dosing was 1-2% of that in brain arachidonic acid. 13C was present in liver and brain cholesterol and in perchloric acid-extractable water-soluble metabolites in the brain, liver and carcass. We conclude that low but measurable amounts of exogenous gamma-linolenic acid do access the suckling rat brain in vivo. The slow time course of [5-13C] arachidonic acid appearance in the brain suggests most of it was probably transported there after synthesis elsewhere, probably in the liver. Some carbon from gamma-linolenic acid is also incorporated into lipid products other than n-6 long-chain polyunsaturated fatty acids.

Animals↗
PubMed1997

Effects of the AT1-selective angiotensin II antagonist, telmisartan, on hemodynamics and ventricular function after cardiopulmonary resuscitation in pigs.

The purpose of this study was to investigate the effects of the angiotensin II (ANG II) antagonist, telmisartan, on hemodynamics, myocardial function and myocardial blood flow during the postresuscitation phase in a porcine model of CPR and to compare these to saline. After 4 min of ventricular fibrillation and 5 min of closed-chest CPR, defibrillation was performed in 16 domestic pigs to restore spontaneous circulation (ROSC). Ten minutes after ROSC, animals were allocated to receive either the ANG II antagonist, telmisartan, at a dose of 1 mg/kg (n = 8) or saline (n = 8). Hemodynamics, myocardial function and myocardial blood flow were measured prearrest and at 5, 30, 90 and 240 min after ROSC. Using a Swan-Ganz catheter with a fast responding-thermistor and a micromanometer tipped catheter, right ventricular end-diastolic and end-systolic volume, right ventricular ejection fraction, left ventricular contractility were 67 +/- 6 ml (mean +/- S.E.M.), 42 +/- 4 ml, 38 +/- 2%, 2036 +/- 77 mmHg/s in the telmisartan group and 82 +/- 2 ml (P < 0.05), 59 +/- 3 ml (P < 0.01), 28 +/- 2% (P < 0.01), 1596 +/- 82 mmHg/s (P < 0.01) in the control group, at 240 min after ROSC. No significant differences in mean aortic and pulmonary artery pressure, cardiac index or myocardial blood flow between the two groups were found. We conclude that the ANG II antagonist telmisartan administered during the postresuscitation phase in pigs increases myocardial contractility without changing cardiac index, systemic vascular resistance, pulmonary vascular resistance, or myocardial perfusion.

Angiotensin Receptor Antagonists↗
PubMed1997

In vivo quantification of endotoxin-induced nitric oxide production in pigs from Na15NO3-infusion.

1. In this investigation the NO production rate is quantified in the pig during normotensive endotoxin-induced shock with increased cardiac output and during subsequent treatment with the NO synthase inhibitor N omega-monomethy-L-arginine (L-NMMA). NO production rate was derived from the plasma isotope-enrichment of 15N-labelled nitrate (15NO3-). 2. Three groups of animals (control, n = 5; endotoxin, n = 6; endotoxin + L-NMMA, n = 6) were anaesthetized and instrumented for the measurement of systemic and pulmonary haemodynamics. Each animal received a primed-continuous infusion of stable, non-radioactively labelled Na15 NO3 (bolus 30 mg, infusion rate 2.1 mg h-1). Arterial blood samples were taken 5, 10, 15, 30, 60 and 90 min later and every 90 minutes until the end of the experiment. 3. Continuous i.v. infusion of endotoxin was incrementally adjusted until mean pulmonary artery pressure (PAP) reached 50 mmHg and subsequently titrated to keep mean PAP approximately 35 mmHg. Hydroxyethylstarch was administered as required to maintain mean arterial pressure (MAP) > 60 mmHg. Six hours after the start of the endotoxin continuous i.v. L-NMMA (1 mg kg-1 h-1) was administered to the endotoxin + L-NMMA group. Haemodynamic data were measured before as well as 9 h after the start of the endotoxin. 4. After conversion of NO3- to nitro-trimethoxybenzene and gas chromatography-mass spectrometry analysis the total NO3- pool, basal NO3- production rate and the increase per unit time in NO3- production rate were calculated from the time-course of the 15NO3- plasma isotope-enrichment. A two compartment model was assumed for the NO3- kinetics, one being an active pool in which newly generated NO3- appears and from which it is eliminated, the other being an inactive volume of distribution in which only passive exchange takes place with the active compartment. 5. Although MAP did not change during endotoxin infusion alone, cardiac output (CO) increased by 42 +/- 40% (P < 0.05 versus baseline) by the end of the experiment due to a significant (P < 0.05 versus baseline) fall in systemic vascular resistance (SVR) to 65 +/- 25% of the baseline value. L-NMMA given with endotoxin did not change MAP, and both CO and SVR were maintained close to the pre-shock levels. 6. Baseline plasma NO3- concentrations were 43 +/- 13 and 40 +/- 10 mumol l-1 in the control and endotoxin animals, respectively, and did not differ at the end of the experiment (39 +/- 8 and 44 +/- 15 mumol l-1, respectively). The mean NO3- pool and basal NO3- production rate were 1155 +/- 294 mumol and 140 +/- 32 mumol h-1, respectively, without any intergroup difference. Endotoxin significantly increased NO3- production rate (23 +/- 10 mumol h-2, P < 0.05 versus control (6 +/- 7 mumol h-2) and endotoxin + L-NMMA groups). L-NMMA given with endotoxin (-1 +/- 2 mumol h-2, P < 0.05 versus control and endotoxin groups) had no effect. 7. Analysis of the time course of the 15NO3- plasma isotope enrichment during primed-continuous infusion of Na15NO3 allowed us to quantify the endotoxin-induced increase in NO3- production rate independently of total NO3- plasma concentrations. Low-dose L-NMMA blunted the increase in NO3- production rate while maintaining basal NO3- formation.

Animals↗
PubMed1997

Morphologic characterization and assessment of mitral regurgitation after repair of atrioventricular defects in children.

Severe postoperative mitral regurgitation renders information on the underlying mechanism before reoperation very important, as a potential for mitral valve reconstruction may facilitate the decision whether to reoperate, especially in the very young. This study compares the efficacy of transthoracic echo-cardiography (TTE) and left-ventricular angiography with that of transesophageal echocardiography (TEE) for detection of the mechanism underlying mitral regurgitation and its quantitative assessment in children after repair of common atrioventricular septal defect. Five children aged 1.5 to 16 years were evaluated by TTE, TEE, and angiography for postoperative mitral regurgitation 1 to 21 months after initial repair. TEE showed septal detachment of the mitral leaflet in four patients and reopening of the mitral cleft in one patient as the cause of mitral regurgitation whereas TTE failed in four and angiography in all patients. TEE allows definite identification of morphologic characteristics of mitral regurgitation and reliable assessment of its severity. Thus redo surgery may be safety performed on the bases of TEE findings alone without confirmation by cardiac catheterization.

Adolescent↗
PubMed1997

Effects of a dobutamine-induced increase in splanchnic blood flow on hepatic metabolic activity in patients with septic shock.

BACKGROUND: Septic shock leads to increased splanchnic blood flow (Qspl) and oxygen consumption (VO2spl). The increased Qspl, however may not match the splanchnic oxygen demand, resulting in hepatic dysfunction. This concept of ongoing tissue hypoxia that can be relieved by increasing splanchnic oxygen delivery (DO2spl), however, was challenged because most of the elevated VO2spl was attributed to increased hepatic glucose production (HGP) resulting from increased substrate delivery. Therefore the authors tested the hypothesis that a dobutamine-induced increase in Qspl and DO2spl leads to increased VO2spl associated with accelerated HGP in patients with septic shock. METHODS: Twelve patients with hyperdynamic septic shock in whom blood pressure had been stabilized (mean arterial pressure > or = 70 mmHg) with volume resuscitation and norepinephrine received dobutamine to obtain a 20% increase in cardiac index (CI). Qspl, DO2spl, and VO2spl were assessed using the steady-state indocyanine green clearance technique with correction for hepatic dye extraction, and HGP was determined from the plasma appearance rate of stable, non-radio-active-labeled glucose using a primed-constant infusion approach. RESULTS: Although the increase in CI resulted in a similar increase in Qspl (from 0.91 +/- 0.21 to 1.21 +/- 0.34l.min-1.m2; P < 0.001) producing a parallel increase of DO2spl (from 141 +/- 33 to 182 +/- 44 ml.min-1.m2; P < 0.001), there was no effect on VO2spl (73 +/- 16 and 82 +/- 21 ml.min-1.m2, respectively). Hepatic glucose production decreased from 5.1 +/- 1.6 to 3.6 +/- 0.9 mg.kg-1.min-1 (P < 0.001). CONCLUSIONS: In the patients with septic shock in whom blood pressure had been stabilized with volume resuscitation and norepinephrine, no delivery-dependency of VO2spl could be detected. Oxygen consumption was not related to the accelerated HGP either, and thus the concept that HGP dominates VO2spl must be questioned in well-resuscitated patients with septic shock.

Adrenergic beta-Agonists↗
PubMed1996

Flush heparin during cardiac catheterisation prevents long-term coagulation activation in children without APC-resistance-preliminary results.

This study was designed to prospectively evaluate haemostatic activation in 75 children undergoing cardiac catheterisation with intermittent flush heparin (10 IU/ml saline) and to relate these data to clinical findings and inherited risk factors for thrombophilia. In addition to flush heparin in infants < 6 months of age in whom additional arterial catheterisation was performed (n = 5) or patients with thrombophilia, heparin (300-400 IU/kg/d) was administered for a further 24 h. APTT was prolonged and anti Xa activity was significantly increased at the end of catheterisation and returned to normal 24 hours later. Whereas thrombin generation (F1 + 2) showed a significant coagulation activation at the end of catheterisation, no concomitant fibrinolytic activation (D-Dimer) was observed. Four children showed resistance to APC: one of them in whom stroke had occurred before and one additional child heterozygous for APCR received further prophylactic heparin. Two neonates with APCR and flush heparin only suffered from thrombosis after catheterisation. No further thrombotic events occurred. This study indicates that low-dose flush heparin during catheterisation may prevent long-term haemostatic activation in children without thrombophilia. Whether further heparin after cardiac catheterisation in children with APCR prevents vascular insults requires a more intensive study.

Adolescent↗