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Biomedical subjects

A E Goetz

Publications and source records attributed to A E Goetz.

At least 37 records · Page 2Linked to original sources

Quantitative imaging of tumour blood flow by contrast-enhanced magnetic resonance imaging.

Tumour blood flow plays a key role in tumour growth, formation of metastasis, and detection and treatment of malignant tumours. Recent investigations provided increasing evidence that quantitative analysis of tumour blood flow is an indispensable prerequisite for developing novel treatment strategies and individualizing cancer therapy. Currently, however, methods for noninvasive, quantitative and high spatial resolution imaging of tumour blood flow are rare. We apply here a novel approach combining a recently established ultrafast MRI technique, that is T(1)-relaxation time mapping, with a tracer kinetic model. For validation of this approach, we compared the results obtained in vivo with data provided by iodoantipyrine autoradiography as a reference technique for the measurement of tumour blood flow at a high resolution in an experimental tumour model. The MRI protocol allowed quantitative mapping of tumour blood flow at spatial resolution of 250 x 250 microm(2). Correlation of data from the MRI method with the iodantipyrine autoradiography revealed Spearman's correlation coefficients of Rs = 0.851 (r = 0.775, P < 0.0001) and Rs = 0.821 (r = 0.72, P = 0.014) for local and global tumour blood flow, respectively. The presented approach enables noninvasive, repeated and quantitative assessment of microvascular perfusion at high spatial resolution encompassing the entire tumour. Knowledge about the specific vascular microenvironment of tumours will form the basis for selective antivascular cancer treatment in the future.

Animals↗

Continuous cardiac output measurements do not agree with conventional bolus thermodilution cardiac output determination.

PURPOSE: To evaluate the performance of two different continuous cardiac output monitoring systems based on the thermodilution principle in critically ill patients. METHODS: Nineteen cardiac surgical patients were randomly assigned to continuous cardiac output monitoring using one of the two systems under study (group I, IntelliCath(TM) catheter, n=9; group II, Opti-Q(TM) catheter, n=10). Each patient was studied over a period of three hours. Conventional bolus thermodilution cardiac output measurements were carried out every 15 min leading to 13 measurements in each patient. The continuous cardiac output values were compared with the bolus thermodilution measurements. Bias (mean difference between continuous and bolus thermodilution) and precision (SD of differences) were calculated as a measure of agreement between the respective continuous method and conventional bolus thermodilution. RESULTS: The range of measured cardiac outputs was 3.8-15.4 L*min(-1) (IntelliCath(TM)) and 3.5-8.3 L*min(-1) (OptiQ(TM)). Bias and precision was 0.06 +/- 0.76 L*min(-1) (IntelliCath(TM)) and -0.04 +/- 0.74 L*min(-1) (OptiQ(TM)), respectively. There was no difference in bias between the two systems (P=0.38). +/- 2 SD of the differences (i.e., 95% of the differences) did not fall within the predetermined limits of agreement of +/- 0.5 L*min(-1). CONCLUSIONS: There was no difference between the two systems regarding the agreement with conventional bolus thermodilution as the standard. A discrepancy between bolus and continuous thermodilution cardiac output measurement techniques above the clinically acceptable limits suggest that they are not interchangeable.

Adult↗

Intensive care after minimally invasive and conventional coronary surgery: a prospective comparison.

OBJECTIVE: The purpose of this study was to compare the intensive care course of patients after minimally invasive coronary surgery to conventional coronary artery bypass grafting. DESIGN: Prospective observational study. SETTING: Intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: One hundred and five patients with two-vessel disease consecutively scheduled for elective coronary bypass surgery were enrolled. INTERVENTIONS: Two techniques of revascularization were performed: the Octopus procedure via median sternotomy without cardiopulmonary bypass (n = 52) and conventional coronary artery bypass grafting CABG (n = 53). MEASUREMENTS AND RESULTS: Three major categories describing the patients' postoperative course were defined: (1) clinical and laboratory findings, i.e., transfusion rate, catecholamine support, duration of ventilation, Simplified Acute Physiology Score II (SAPS II), serum levels of cardiac enzymes and lactic acid; (2) postoperative complications, i.e., incidence of myocardial infarction (MI), atrial fibrillation (AF), and neurological deficits; (3) this category was defined as "the extent of care" as represented by the Therapeutic Intervention Scoring System (TISS), and the length of stay in the ICU and in the hospital. In the Octopus group significantly lower figures were noted for duration of ventilation [6.1(5.5/9.5) vs 10.2(8.2/11.8) h], cardiac enzymes (CK-MB-Mass [5.1(2.0/8.3) vs 31.3(21.4/39.3) ng/ml], and lactic acid [2.0(1.5/3.3) vs 3.2(2.2/6.5) mmol/l]), incidence of AF (2/52 vs 9/53), and neurological deficits (0/52 vs 4/53), TISS score [72(44/83) vs 84(73/93)], LOS in the ICU [2(1/2) vs 2(2/2) days], and in the hospital [6(5/9) vs 9(8/12) days]. Catecholamine support, SAPS II scores, and incidence of MI of each group did not differ significantly. CONCLUSIONS: Off-pump coronary surgery via the Octopus technique was superior to conventional CABG regarding the course of patients in the early postoperative period. This implies benefits for the patients and the entire healthcare system.

APACHE↗

Effects of intravenous fat emulsions on lung function in patients with acute respiratory distress syndrome or sepsis.

OBJECTIVE: To investigate whether rapid or slowly infused intravenous fat emulsions affect the ratio of prostaglandin I2/thromboxane A2 in arterial blood, pulmonary hemodynamics, and gas exchange. DESIGN: Prospective, controlled, randomized, crossover study. SETTING: Operative intensive care unit of a university hospital. PATIENTS: Eighteen critically ill patients. Ten patients were stratified with severe sepsis, and eight patients had acute respiratory distress syndrome (ARDS). INTERVENTIONS: Patients were assigned randomly to receive intravenous fat emulsions (0.4 x resting energy expenditure) over 6 hrs (rapid fat infusion) or 24 hrs (slow fat infusion) along with a routine parenteral nutrition regimen, by using a crossover study design. MEASUREMENTS AND MAIN RESULTS: Systemic and pulmonary hemodynamics as well as gas exchange measurements were recorded via respective indwelling catheters. Arterial thromboxane B2 and 6-keto-prostaglandin-F1alpha plasma concentrations were obtained by radioimmunoassay, and 6-keto-prostaglandin-F1alpha/thromboxane B2 ratios (P/T ratios) were calculated. Data were collected immediately before and 6, 12, 18, and 24 hrs after onset of fat infusion. In the ARDS group, P/T ratio increased by rapid fat infusion. Concomitantly, pulmonary shunt fraction, alveolar-arterial oxygen tension difference [P(a-a)o2]/Pao2, and cardiac index increased as well, whereas pulmonary vascular resistance and Pao2/Fio2 declined. After slow fat infusion, a decreased P/T ratio was revealed. This was accompanied by decreased pulmonary shunt fraction, lowered P(a-a)o2/Pao2, and increased Pao2/Fio2. Correlations between plasma concentrations of 6-keto-prostaglandin-F1alpha or thromboxane B2 and measures of respiratory performance could be shown during rapid and slow fat infusion, respectively. In the sepsis group, the P/T ratio remained unchanged at either infusion rate, but pulmonary shunt fraction and P(a-a)o2/Pao2 decreased after rapid fat infusion, whereas Pao2/Fio2 increased. CONCLUSION: Pulmonary hemodynamics and gas exchange are related to changes of arterial prostanoid levels in ARDS patients, depending on the rate of fat infusion. In ARDS but not in sepsis patients clear of pulmonary organ failure, a changing balance of prostaglandin I2 and thromboxane A2 may modulate gas exchange, presumably via interference with hypoxic pulmonary vasoconstriction.

APACHE↗

Neoadjuvant photodynamic therapy before curative resection of proximal bile duct carcinoma.

BACKGROUND: Hilar bile duct carcinoma has an 80% probability of local recurrence after curative resection, which might be reduced if neoadjuvant photodynamic therapy is feasible. CASE AND TREATMENT: After intravenous injection of sodium porfimer we treated an adenocarcinoma of the proximal common bile duct (T2 N0 M0, Bismuth type II) in a 72-year-old man with red laser light (applied from the lumen at a dose 250 Joules/cm2), and the adjacent right and left hepatic and common bile duct at a dose of 125 Joules/cm2. After 23 days the tumor was completely resected (adenocarcinoma pT2 pNO; G2). RESULTS: In the lumenal, 4-mm-thick layer the bile duct specimen exhibited complete tumor necrosis with pigmentation of photodegraded porfimer and no viable tumor cells, while in the outer layer of the wall (at 5-8-mm depth) viable cancer cell nests without degraded porfimer were seen. The bile duct tissue showed little damage. Eighteen months after surgery, neither tumor recurrence nor stricture formation was found at the pretreated bilioenteric anastomoses. CONCLUSIONS: a) Photodynamic therapy with sodium porfimer seems to be confined to the superficial 4-mm layer of bile duct cancer. b) Neoadjuvant photodynamic therapy is feasible for hilar bile duct carcinoma.

Adenocarcinoma↗

Beat-to-beat measurement of cardiac output by intravascular pulse contour analysis: a prospective criterion standard study in patients after cardiac surgery.

OBJECTIVE: To evaluate the accuracy of a new pulse contour method of measuring cardiac output in critically ill patients. DESIGN: A prospective criterion standard study. SETTING: Cardiac surgery intensive care unit in a university hospital. PARTICIPANTS: Nineteen cardiac surgery patients requiring intensive care treatment with pulmonary artery catheters after surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The pulse contour cardiac output monitor uses transpulmonary bolus thermodilution measurements to calibrate the system. In each patient, the pulse contour cardiac output values were compared with conventional thermodilution. The method described by Bland and Altman and linear regression analysis were used for comparison. The mean difference (bias) +/- standard deviation of differences (precision) was 0.31 +/- 1.25 L/min for pulmonary bolus thermodilution cardiac output versus pulse contour cardiac output and 0.21 +/- 0.73 L/min for pulmonary bolus thermodilution cardiac output versus transpulmonary bolus thermodilution cardiac output. Linear regression (correlation) analyses were pulse contour cardiac output = 0.97 thermodilution + 0.53 (r = 0.88), and transpulmonary cardiac output = 0.87 thermodilution + 1.09 (r = 0.96). There was a small increase 60 minutes after recalibration but not a statistically significant difference between pulse contour cardiac output and pulmonary bolus thermodilution cardiac output (p = 0.52). CONCLUSIONS: Bias and precision are acceptable, and the system provides results that agree with conventional thermodilution. This study demonstrates the clinical applicability of the pulse contour cardiac output monitoring system.

Adult↗

Intermittent atrial level right-to-left shunt with temporary hypoxemia in a patient during support with a left ventricular assist device.

We report a 56-year-old male patient developing hypoxemia after surgical replacement of infected valves of a left ventricular assist device (LVAD, Novacor) which had supported him during the previous 15 months. Contrast transesophageal echocardiography (TEE) revealed an atrial septal defect with intermittent right-to-left shunt across a patent foramen ovale. We postulate that the shunt detected in this patient occurred as a consequence of reduced pulmonary vascular compliance due to positive end-expiratory pressure (PEEP) and an increase of mean intrathoracic pressure. Furthermore, we hypothesize that synchronized LVAD operation exacerbates any potential right-to-left shunt due to the profound left ventricular unloading which occurs during LVAD support. In this first report of a right-to-left shunt from a previously unrecognized patent foramen ovale in a Novacor patient, the subsequent transient hypoxemia could be managed by avoiding PEEP of more than 3 mmHg, and mean airway pressure of more than 11 mmHg and by careful volume replacement in order to prevent the pump from completely emptying the left ventricle (LV) and the left atrium (LA). Thus, prior to every LVAD implantation a transesophageal contrast echocardiography with Valsalva maneuver should be performed to identify intracardiac right-to-left shunt.

Heart Septal Defects, Atrial↗

Health-related quality of life and post-traumatic stress disorder in patients after cardiac surgery and intensive care treatment.

OBJECTIVES: Health-related quality of life and patient satisfaction have become important end points in cardiac surgery. Post-traumatic stress disorder has been described in patients with life-threatening heart disease. In this study, we investigated the occurrence of post-traumatic stress disorder in a sample of patients after cardiac surgery and compared health-related quality of life and patient satisfaction between patients with and without evidence of post-traumatic stress disorder. METHODS: We studied 80 patients serially admitted to the intensive care unit after cardiac surgery (bypass grafting, n = 51; aortic valve replacement, n = 29). Health-related quality of life was assessed with the use of the SF-36 Health Status Questionnaire. Post-traumatic stress disorder was measured with a previously validated instrument (the Post-Traumatic Stress Syndrome 10-Questions Inventory), and 20 different aspects of life satisfaction were quantified on a scale ranging from 0 to 10. For measurements of health-related quality of life and post-traumatic stress disorder, age- and gender-comparable healthy individuals, as well as patients with cardiovascular diseases, served as control groups. RESULTS: Patients who had cardiac surgery described high life satisfaction summary scores (156 of a maximum of 200 points) and only small impairments in physical and mental SF-36 summary scores when compared with healthy control groups (median reduction 7.15, P <.05). Patients with evidence of post-traumatic stress disorder (n = 15) reported the lowest SF-36 mental health summary scores when compared with patients without stress disorder (38.3 vs 48.4, P =.004) and rated their life satisfaction lower (121.5 vs 162.0, P =.002). CONCLUSIONS: Patients who have had cardiac surgery demonstrate a high life satisfaction with an acceptable degree of physical and mental health-related quality of life. Impairments in psychosocial function and life satisfaction were found in a subgroup of patients with evidence of post-traumatic stress disorder.

Aged↗

Role of L-selectin in leukocyte sequestration in lung capillaries in a rabbit model of endotoxemia.

After a variety of pathophysiologic stimuli, neutrophils accumulate in lung capillaries and contribute to the pathogenesis of acute lung injury. Lung neutrophil sequestration has previously been attributed to mechanical retention of stiffened neutrophils, but L-selectin-mediated leukocyte/endothelial interaction may be an essential step. We investigated the effect of the anti-L-selectin antibody HuDreg 200 on leukocyte sequestration and microhemodynamics in alveolar capillaries in a model of acute endotoxemia. We used in vivo fluorescence microscopy to analyze kinetics of fluorescently labeled red and white blood cells in alveolar capillary networks of the rabbit lung. Investigations were performed over 2 h after an intravenous infusion of 0.2 ml/kg body weight (bw) NaCl, 2 mg/kg bw HuDreg 200, 20 microg/kg bw lipopolysaccharide (LPS) of Escherichia coli 0111:B4, or the combination of HuDreg 200 and LPS, respectively. Infusion of LPS induced leukocyte sequestration in alveolar capillaries, which was accompanied by a reduction of alveolar capillary perfusion and functional capillary density. These effects could be completely blocked by pretreatment of animals with HuDreg 200. We conclude that L-selectin-mediated leukocyte/endothelial interaction is a necessary prerequisite for leukocyte sequestration in alveolar capillaries in this model. Impaired alveolar capillary perfusion appeared to result directly from capillary leukocyte sequestration.

Acute Disease↗

Measurement of respiratory impedance by impulse oscillometry--effects of endotracheal tubes.

Impulse Oscillometry is a new, noninvasive method to measure respiratory impedance, i.e. airway resistance and reactance at different oscillation frequencies. These parameters are potentially useful for the monitoring of respiratory mechanics in the critically ill patent with respiratory dysfunction. The endotracheal tube, used to mechanically ventilate these patients, however, represents an additional nonlinear impedance that introduces artifacts into the measurements. The objective of this work was therefore to investigate the effects of clinically available endotracheal tubes on resistance and reactance of an in vitro analogue of the respiratory system. Additionally, the effects of decreasing the compressible gas volume in this experimental model, as a simulation of decreased lung capacity and compliance, was investigated. Impulse oscillometric measurements of the test analogue gave highly reproducible results with and without an endotracheal tube. The tubes had significant influence on the measurement of the test object at all frequencies investigated. Changes of low frequent reactance were negligible - at least if repetitive measurements of the same system are performed - for realistic measurement of airway resistance, a correction of the tube impedance or measurement of the pressure distal of the tube is required. Resistance increased and low frequent reactance decreased significantly with decreasing gas volume. These changes were of magnitudes higher than the variations due to the introduction of the endotracheal tubes. Our results suggest that changes of respiratory reactance measured with impulse oscillometry may be used as a monitoring parameter in intubated patients.

Airway Resistance↗

Dosage of inhaled nitric oxide: a simple method for experimental studies.

Few studies on treatment with inhaled nitric oxide (NOi) have been carried out in small laboratory animals yet, since commercially available dosing devices are not appropriate in this setting for technical or financial reasons. The aim of our study was to establish and validate a simple, cost-effective system for the application of NOi in small animals. The system mixes NOi with constant-flow inspiratory gas. A gas blender allows for a mixture of nitrogen, oxygen, and NO dissolved in nitrogen. A formula using the desired inspiratory oxygen fraction and the desired concentration of NOi as independent variables derives a somewhat higher inspiratory oxygen fraction, which is preset using an oximeter. Then the flow of NO in nitrogen is started, lowering the inspiratory oxygen fraction to the initially desired value, thereby adding NOi in the desired concentration. The method was validated by 153 adjustments, covering a variety of oxygen fractions and concentrations of NOi. NOi was measured by chemiluminescence as reference method. A close correlation (R = 0.994) was found, and the regression line was close to the line of identity with y = -0.0994 + 1.048x. No systematic errors could be identified. We conclude that the method described may serve as a simple, cost-effective way to administer NOi to small animals.

Administration, Inhalation↗

Validation of MR thermometry technology: a small animal model for hyperthermic treatment of tumours.

BACKGROUND: Local hyperthermia has been shown to be an effective adjuvant therapy for cancer. However, progress in this treatment modality requires the non-invasive assessment of temperature distribution in the entire tumour to enable administration of an efficient thermal dose to all tumour areas. Magnetic resonance (MR) imaging offers a promising tool to quantify, non-invasively and three-dimensionally, temperature distribution within tumours. An animal model taking into account the complex interrelationship between pathophysiological changes within a tumour during hyperthermia and temperature-sensitive MR parameters is warranted for the development and validation of new MR thermometry technology. METHODS: An experimental set-up was implemented to allow simultaneous measurements of temperature, tumour blood flow and temperature-sensitive MR parameters under standardised conditions in vivo. Local hyperthermia was induced at 44 degrees C for 20 min under inhalation anaesthesia on seven Syrian Golden hamsters bearing an amelanotic melanoma. Fibreoptic probes were used for reference temperature measurements. Laser Doppler flowmetry served for on-line tumour blood flow determination, and MR thermometry was performed using longitudinal T1 relaxation time measurements. RESULTS: The experimental design enables multifunctional MR thermometry. T1 relaxation times of tumours were 1.44 s (1.36, 1.46) and 1.53 s (1. 48, 1.75) at 37 degrees C and during hyperthermia at 44 degrees C, respectively (median, 25% and 75% quartiles, respectively; P<0.05). At the end of 20 min of hyperthermic treatment at 44 degrees C, relative tumour blood flow was reduced to 40.5% (20.7, 43.3) compared to values before treatment (median, 25% and 75% quartiles, respectively; P<0.05). Imaging of T1 relaxation times revealed a heterogeneous distribution in temperature during hyperthermic treatment. CONCLUSION: This novel in vivo model allows standardised investigations for the development and validation of MR thermography methods.

Animals↗

Active and higher intracellular uptake of 5-aminolevulinic acid in tumors may be inhibited by glycine.

Topical 5-aminolevulinic acid is used for the fluorescence-based diagnosis and photodynamic treatment of superficial precancerous and cancerous lesions of the skin. Thus, we investigated the kinetics of 5-aminolevulinic acid-induced fluorescence and the mechanisms responsible for the selective formation of porphyrins in tumors in vivo. Using amelanotic melanomas (A-Mel-3) grown in dorsal skinfold chambers of Syrian golden hamsters fluorescence kinetics were measured up to 24 h after topical application of 5-aminolevulinic acid (1%, 3%, or 10%) for 1 h, 4 h, or 8 h by intravital microscopy (n = 54). Maximal fluorescence intensity in tumors after 1 h application (3% 5-aminolevulinic acid) occurred 150 min and after 4 h application (3% 5-aminolevulinic acid) directly thereafter. Increasing either concentration of 5-aminolevulinic acid or application time did not yield a higher fluorescence intensity. The selectivity of the fluorescence in tumors decreased with increasing application time. Fluorescence spectra indicated the formation of protoporphyrin IX (3% 5-aminolevulinic acid, 4 h; n = 3). The simultaneous application of 5-aminolevulinic acid (3%, 4 h) and glycine (20 microM or 200 microM; n = 10) reduced fluorescence in tumor and surrounding host tissue significantly. In contrast, neither decreasing iron concentration by desferrioxamine (1% and 3%; n = 10) nor inducing tetrapyrrole accumulation using 1, 10-phenanthroline (7.5 mM; n = 5) increased fluorescence in tumors. The saturation and faster increase of fluorescence in the tumor together with a reduction of fluorescence by the application of glycine suggests an active and higher intracellular uptake of 5-aminolevulinic acid in tumor as compared with the surrounding tissue. Shorter application (1 h) yields a better contrast between tumor and surrounding tissue for fluorescence diagnosis. The additional topical application of modifiers of the heme biosynthesis, desferrioxamine or 1,10-phenanthroline, however, is unlikely to enhance the efficacy of topical 5-aminolevulinic acid-photodynamic therapy at least in our model.

Aminolevulinic Acid↗

Recombinant human growth hormone for reconditioning of respiratory muscle after lung volume reduction surgery.

OBJECTIVE: To investigate the effects of recombinant human growth hormone (rHGH) as a "rescue treatment" in an end-stage chronic obstructive pulmonary disease patient after prolonged weaning failure. DESIGN: Descriptive case report. SETTING: Fifteen-bed intensive care unit in a university hospital. PATIENT: A 62-year-old man with end-stage chronic obstructive pulmonary disease and pulmonary emphysema after lung reduction surgery and prolonged weaning failure after long-term mechanical ventilation. INTERVENTIONS: After 42 days of unsuccessful weaning from the respirator, rHGH (27 IU/day, 0.3 IU/kg body weight/day) was administered for 20 days through a subcutaneous injection in addition to standard intensive care. MEASUREMENTS AND MAIN RESULTS: In addition to daily routine laboratory studies, the visceral proteins prealbumin, retinol-binding protein, and transferrin, and nitrogen balance were measured twice a week, as were the thyroid hormones triiodothyronine, thyroxine, and thyroid-stimulating hormone, plasma insulin levels, and the insulin-like growth factor (IGF)-1 binding proteins IGF-BP1 and IGF-BP3. IGF-1 was measured from day 1 to day 4 of rHGH administration. Nutritional support was guided by indirect calorimetry. Additionally, weaning variables such as peak expiratory flow rate and expiratory tidal volume were measured noninvasively. T-piece weaning trials were carried out daily until respiratory muscle fatigue occurred. IGF-1 increased in response to rHGH stimulation, from 103 to 230 microg/mL, within 4 days. The carrier protein IGF-BP3 increased from 126 to 283 mg/L at the end of the study period, and the inhibiting IGF-BP1 decreased initially from 19 to 14 mg/L and then increased until the end of the study to 31 mg/L. Nitrogen balance increased initially from 4.6 to 13.6 g/24 hrs and thereafter decreased until the end of rHGH treatment to 8.3 g/24 hrs. Resting energy expenditure increased from 1800 to 2300 kcal/24 hrs. Peak expiratory flow rate increased from 0.69 to 0.88 L/sec. The expiratory tidal volume showed a slight increase during the study period during the daily decrease of pressure support on the ventilator setting. Respiratory muscular strength increased beginning 10 days after rHGH therapy was started. From this point, T-piece weaning trials could be prolonged almost daily. The patient was extubated successfully on postoperative day 75. CONCLUSIONS: This case report shows that after a prolonged catabolic state and long-term mechanical ventilation, administration of rHGH not only enhances the response of protein metabolism but improves respiratory muscular strength. Therefore, it may reduce the duration of mechanical ventilation in selected patients.

Energy Metabolism↗