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Biomedical subjects

P Stadler

Publications and source records attributed to P Stadler.

At least 19 recordsLinked to original sources

Effects of two different dosages of dobutamine on pulmonary artery wedge pressure, systemic arterial blood pressure and heart rate in anaesthetized horses.

The purpose of the present study was to investigate the effects of two different dobutamine concentrations on pulmonary artery wedge pressure (PAWP) and on mean systemic arterial blood pressure (MAP) in horses anaesthetized with isoflurane, after induction of general anaesthesia with xylazine, ketamine and diazepam. Eight healthy warm-blood horses were included in the study. Each horse was subjected to general anaesthesia twice with two different dosages of dobutamine, 3 and 5 microg/kg bw/min, being infused over 15 min, starting 50 min after induction of general anaesthesia (T(0)). The heart rate, the PAWP and the MAP were recorded after 10 min (T(1)) and then every 5 min until 15 min after cessation of intravenous dobutamine administration (T(3)-T(5)). The PAWP was measured by a right heart catheter, which was positioned in the pulmonary capillaries. Mean systemic arterial blood pressure was monitored at the facial artery for the duration of general anaesthesia. All parameters increased at both dosage rates of dobutamine and decreased significantly when dobutamine administration ceased. The increase in heart rate was significantly higher after administration of 3 microg/kg bw/min dobutamine compared with the dosage of 5 microg/kg bw/min dobutamine. The increase in MAP was also higher at this dosage, but not significantly different to the dosage of 5 microg/kg bw/min dobutamine. During both dosages the MAP was above a value considered to be compatible with good peripheral circulation. The greater increase in PAWP was observed during administration of 5 g/kg bw/min dobutamine, but PAWP was not significantly different with the dosage of 3 microg/kg bw/min dobutamine. In conclusion, the administration of dobutamine led to an increase in MAP and PAWP above a value considered to be compatible with a good peripheral circulation. The results of the present study indicate that dobutamine improves circulation, in addition to its well-known effect on the periphery.

Adrenergic beta-Agonists↗

[Pulmonary artery wedge pressure and heart rate measurement during pharmacological stress induction for left cardial function diagnosis in horses with and without heart disease].

In 18 horses, the pulmonary artery wedge pressure and the heart rate were measured during pharmacological stress load. 12 horses were healthy (4 trained, 8 untrained) and 6 horses had a heart disease (3 trained, 3 untrained). Pharmacological stress induction was carried out with the sympathomimetic drug dobutamine at a dosage rate of 7.5 microg/kg/min over 10 minutes of infusion. At the fourth minute, the parasympatholytic drug atropine was administered (5 microg/kg bw), and the heart rate and the pulmonary artery wedge pressure were continuously measured over 26 minutes. During sole dobutamine infusion, a significant decrease in heart rate and a significant increase in pulmonary artery wedge pressure were observed. After the application of atropine in the fourth minute, a significant increase in heart rate (from 35.7 +/- 6 up to 106 +/- 38/ min) and in pulmonary artery wedge pressure (from 15.7 +/- 3 up to 24 +/- 8.6 mmHg) were visible in the group of healthy horses. The horses with heart diseases had a significantly higher increase in both parameters (heart rate and pulmonary artery wedge pressure) with a significantly positive correlation (r = 0.7). The heart rate increased in the horses with heart diseases from 35.2 +/- 2,8 beats/min up to 132 +/- 45.7 beats/min and the pulmonary artery wedge pressure increased from 17.3 +/- 3,2 mmHg up to 32.7 +/- 13 mmHg. The cardiac status (healthy or heart disease) as well as the training level of the horses (untrained or trained) had a significant influence on the heart rate and the pulmonary artery wedge pressure. The untrained horses (healthy and heart disease) showed significantly higher values over a longer period of time than did the trained horses with the same cardiac status. Additionally the influence of pharmacological stress induction on echocardiographic parameters was investigated. The left atrial size (p = 0.015) and left ventricular diameter were significanly different in the systole (p = 0.008) and in the diastole (p = 0.001) between healthy horses and horses with heart diseases. All horses showed a positive correlation between the pulmonary artery wedge pressure and the left atrial size (r = 0.8), as well as between the left ventricular systolic (r = 0.6) and the diastolic diameter (r = 0.6). The correlation between the pulmonary artery wedge pressure and the left atrial size was nearly the same in the healthy horses (r = 0.74) and in the horses with heart diseases (r = 0.76). Regarding the training level, all untrained horses had a significantly higher correlation between the pulmonary artery wedge pressure and the left atrial size (r = 0.87) in comparison to the trained horses (r = 0.74). Particularly in the untrained horses with heart diseases, this correlation was remarcable (r = 0.99).

Animals↗

[Precision-controlled echocardiographic left ventricular function parameters by repeated measurement on three consecutive days in trained and untrained warmblood horses].

Echocardiographic measurements have to be reliable and reproducible with only a low day to day variability for detecting pathological changes of left ventricular myocardial function in horses. The day dependent fluctuation margin represents an important indicator for the reproducibility of a method. To find out the day to day variability of echocardiographic parameter in healthy warmblood horses, in the present study repeated echocardiographic measurements at three consecutive days were carried out (at the same time and by the same examiner) at 11 untrained and 7 trained warmblood horses. The horses were examined from the right hemithorax, in five different B- and M-Mode views in the long and short heart axis. The echocardiographic measurements in the three-day examination interval showed with coefficient of variation between 3.4 and 25.8% a good reproducibility. In order to calculate the precision of echocardiographic parameters (reproducibility from day to day) statistical analysis was carried out by means of a linear model with random effects. Herefor the variation between repeated measurements over three days and within the horses (day to day intraindividual variation) as well as the variation between the horses (interindividual variation) were taken into account. In dependency of the echocardiographic parameters 46.2-95.7% (median 85.7%) of the variation is caused by the difference between the horses (intraclass correlation) and 4.3-53.8% (median 14.3%) of the variation is caused by the repeated measurements on different days. With a coefficient of variance from 6.6% and an intraclass correlation of 0.957 the left ventricular diastolic diameter at the level of the papillary muscles showed the lowest variation between repeated measurements on different days. The heart rate with a coefficient of variance of 10.3% and an intraclass correlation of 0.462 showed the highest variation with 53.8% between the repeated measurements on different days. The precision of single echocardiographic measurements is confirmed. All parameters were also tested for differences between trained and untrained horses. Significant differences (p<0.05) could be found in the left ventricular diameter at the level of the apex cordis and under the mitral valves as well as in the systolic left ventricular area.

Animals↗

A new tool to monitor training and performance of sport horses using global positioning system (GPS) with integrated GSM capabilities.

Global Positioning Systems (GPS) are considered suitable to monitor the position and velocity of horses during cross-country competition or in training. Furthermore, simultaneous recording of life data such as heart rate could be useful to assess the horse's condition during exercise. To test the suitability and reliability of a commercially available GPS system with integrated heart rate recording system and with built in GSM for data transmission, the Fidelak Equipilot Type EP-2003-15/G-2.11 (EP-15/G) was evaluated first for reliability of pulse recording from a pulse generator within the physiological range of horses; furthermore distance, velocity and heart rate recordings were carried out on a standard 1000 m field track with five repetitions. Agreement (% deviation from actually measured distance and from stopwatch-distance based velocity calculations) and variability (Coefficient of Variation for distance, velocity, heart rate) were calculated. From the results it was safe to assume that the heart rate sensor recorded horse heart rates at a high degree of accuracy. Overall distances and velocities are in high agreement with actually measured values. However, overall variability expressed in terms of relative variability (C.V.) is smaller for distance recording (C.V. 0.68%) when compared to velocity (C.V. 1.01%). The system tested is suitable and reliable for simultaneously recording of distance, velocity and heart rates for horses during cross country exercise. GPS-based monitoring of movement along with simultaneous recording of physiological data and the possibility to call upon data will not only be of benefit for training horses or for surveillance during competition, it may also be suitable for distant patient monitoring and in behavioural studies as well as in veterinary medicine in general.

Animals↗

Pulmonary artery wedge pressure measurement in healthy warmblood horses and in warmblood horses with mitral valve insufficiencies of various degrees during standardised treadmill exercise.

In 12 healthy warmblood horses and 10 horses with mitral valve insufficiencies (MVI) of various degrees heart rate and pulmonary artery wedge pressure (PWP) was measured at rest and during standardised exercise on a high speed treadmill. There was a significant increase in PWP with each change in speed of the treadmill (p < 0.01). The PWP of horses with mild mitral valve regurgitation under working conditions was not significantly different compared to the healthy horses. The horses with moderate mitral valve regurgitation showed a significant higher pulmonary artery wedge pressure at rest and during exercise compared to the healthy horses (p < 0.01) at rest and during treadmill velocity. The tendencies were seen that mild mitral valve regurgitation results only in mild hemodynamic changes during exercise, while moderate MVI have an important influence on haemodynamics.

Animals↗

Comparison of systolic cardiac function before and after treatment of atrial fibrillation in horses with and without additional cardiac valve insufficiencies.

Clinical, electrocardiographic and echocardiographic examinations were conducted before therapy and 4 days after conversion to normal sinus rhythm in 15 horses with a history of atrial fibrillation of 2-6 months duration. Seven horses showed no other signs of cardiac disease. Four horses suffered additionally from mitral valve insufficiency, while six horses had aortic valve insufficiency, including two of the four horses with mitral valve insufficiency, but none had signs of congestive heart failure. Doppler echocardiographic estimates of various variables were made for assessment of systolic heart function. These included heart rate, stroke volume, cardiac output and cardiac output per kg of body weight (heart index). After conversion to normal sinus rhythm, the horses without heart valve insufficiency showed a statistically significantly decreased heart rate (-24%) and cardiac output (-3%), but an increase in stroke volume (+8.4%) and heart index (+9%). The horses with heart valve insufficiency experienced a statistically significant decrease in heart rate (-21%) after conversion to normal sinus rhythm, but showed an increase in all other variables. Cardiac output increased statistically significantly by 20%, stroke volume by 54% and heart index by 58%.

Animals↗

[Influence of detomidine on echocardiographic function parameters and cardiac hemodynamics in horses with and without heart murmur].

30 warmblood horses were examined before and after sedation with 20 micrograms/kg BW detomidine, to determine changes of cardiac function parameters, using B-mode, M-mode and Doppler echocardiography. 15 horses showed a heart murmur, but no clinical signs of cardiac heart failure, 15 horses had neither a heart murmur nor other signs of cardiac disease. After sedation with detomidine we could recognise a significant increase of end-diastolic left atrium diameter, an increase of end-systolic left ventricular diameter and aortic root diameter. The end-systolic thickness of papillary muscle and interventricular septum showed a decrease. Fractional shortening and amplitude of left ventricular wall motion was decreased after sedation. The mitral valve echogram revealed a presystolic valve closure and an inflection in the Ac slope (B-notch) in xy horses before sedation. Both increased after sedation with detomidine. Doppler echocardiography showed a decrease of blood flow velocity and velocity time integral (VTI) in the left and right ventricular outflow tract after sedation. Regurgitant flow signals were intensified following sedation in xy horses, especially at the mitral valve.

Animals↗

Effects of the ACE inhibitor quinapril on echocardiographic variables in horses with mitral valve insufficiency.

Twenty horses with mitral valve insufficiency, but without signs of congestive heart failure, and five horses without signs of heart disease were examined before and after medication with an angiotensin-converting enzyme (ACE) inhibitor. The examination included echocardiography assessment as well as heart catheterization. The echocardiographic examination included B-mode, M-mode, conventional and colour Doppler techniques. For 8 weeks, all horses were treated with Accupro 20 (active substance: Quinapril) at an oral dose rate of 120 mg/horse/day. A follow-up of the horses with mitral valve insufficiency after 8 weeks revealed a statistically significant increase in the stroke volume and the cardiac output as well as a decrease in regurgitation velocity time integral (VTI). The regurgitation blood velocity remained the same. The severity of mitral valve insufficiencies revealed a moderate improvement in five horses, from moderate to mild, after therapy. Significant changes of cardiac dimension (B-mode) and shortening fraction (M-mode) before and after treatment could not be observed. The owners' judgement of the horses' performance was that of a minor improvement. In the horses without clinical findings the results of examination before and after treatment remained the same.

Angiotensin-Converting Enzyme Inhibitors↗

[Pulmonary wedge pressure and heart frequency measurements during standardized treadmill exercise for extension of left atrial function diagnosis in warmblood horses].

In 12 healthy warmblood horses (six trained and six untrained) the pulmonary wedge pressure and heart frequency was measured at rest and during a standardised exercise test on a treadmill. The mean pulmonary wedge pressure at rest was 14.53 +/- 2.36 mmHg. There was no significant difference in pulmonary wedge pressure either at rest or during exercise between trained and untrained horses. During walking (1.8 m/s) the mean pulmonary wedge pressure was 19.62 +/- 4.03 mmHg, during trotting (4 und 5 m/s) it was between 22.38 +/- 3.92 mmHg and 25.28 +/- 3.7 mmHg. During canter (6 m/s) and gallop (8 m/s) the mean pulmonary wedge pressure increased to a level of 25.54 +/- 4.3 mmHg and 31.86 +/- 4.29 mmHg. There was a significant increase in pulmonary wedge pressure with each incremental step of the standardised treadmill test. Concerning mean heart frequency a highly significant increase could be observed at the beginning and at the end (treadmill speed of 7 and 8 m/s) of the standardised exercise test. At higher intensity of the exercise test (7 m/s and 8 m/s) untrained horses showed a significantly increased heart rate compared to trained horses. Neither at rest nor during the different exercise levels a significant correlation factor greater 0.5 between heart frequency and pulmonary wedge pressure could be observed. The increase of heart frequency and pulmonary wedge pressure during exercise showed no correlation. Between left atrial size and pulmonary wedge pressure a statistical weak correlation could be observed up to a treadmill velocity of 6 and 7 m/s.

Animals↗

Tumor hypoxia, p53, and prognosis in cervical cancers.

BACKGROUND: The p53 protein is involved in the regulation of initiation of apoptosis. In vitro, p53-deficient cells do not respond to hypoxia with apoptosis as do p53-normal cells, and this may lead to a relative growth advantage of cells without a functioning p53 under hypoxia. On the basis of this hypothesis, a selection of cells with a functionally inactive p53 may occur in hypoxic tumors. The development of uterine cervical carcinomas is closely associated with infections of human papilloma viruses, which may cause a degradation of the tumor suppressor gene p53, resulting in a restriction of apoptosis. Thus, cervical cancers have often a functionally inactive p53. The purpose of our clinical study was therefore to investigate the association between p53, hypoxia, and prognosis in cervical cancers in which the oxygenation status can be determined by clinical methods. MATERIAL AND METHODS: Seventy patients with locally advanced squamous cell cervical cancer Stages IIB (n = 14), IIIB (n = 49), and IVA (n = 7) were investigated in the period from 1996 through 1999. All were treated with definitive radiotherapy with curative intent by a combination of external radiotherapy plus high-dose-rate afterloading. Before therapy, tumor oxygenation was measured with a needle probe polarographically using the Eppendorf histograph. Hypoxic tumors were defined as those with pO(2) measurements below 5 mm Hg (HF5). Pretreatment biopsies were taken and analyzed immunohistologically for p53 protein expression with the DO-7 antibody. The DNA index was measured by flow cytometry. The statistical data analysis was done with SPSS 9.0 for Windows. RESULTS: The 3-year overall survival was 55% for the whole group of patients. Clinical prognostic factors in a multivariate analysis were pretreatment hemoglobin level (3-year survival 62% for patients with a pretreatment hemoglobin > or =11 g/dl vs. 27% for hemoglobin <11 g/dl, p = 0.006) and FIGO stage (Stage IIB: 65%; Stage IIIB: 60%; Stage IVA: 29%, p = 0.01). Sixty of the 70 tumors showed positive immunohistologic staining for p53 protein (transformed p53 = tp53), and 10/70 were negative (wild-type p53 = wtp53); p53 expression had no significant impact on survival (50% for tp53 vs. 79% for wtp53, p = 0.11). FIGO stage and anemia had no impact on p53 expression. Forty-nine of 70 tumors were hypoxic (HF5+), and 21 showed no hypoxia (HF5-). Hypoxic carcinomas were more frequently positive for p53 as compared to nonhypoxic tumors (27% vs. 13%, p = 0.011) and showed a trend toward a lower survival (48% vs. 70%, p = 0.07). In a further multivariate analysis, the impact of a combination of p53 expression and hypoxia on survival was examined. After adjusting for FIGO stage and pretreatment anemia, patients with wtp53 tumors had the best prognosis (3-year survival 79%) followed by tp53-HF5(-) patients (57%), and the most unfavorable prognosis was observed for tp53-HF5(+) patients (47%). The DNA index was higher in tp53 carcinomas compared to wtp53 tumors, 1.97 +/- 0.4 vs. 1.67 +/- 0.1, p = 0.05. The highest DNA index was found in hypoxic tumors with transformed p53 (2.2 +/- 3.1). CONCLUSIONS: Advanced stage and pretreatment hemoglobin level are independent prognostic factors in cervical carcinomas. The immunohistologic detection of (a functionally inactive) p53 and the presence of hypoxia had no prognostic impact, if analyzed as single parameters. However, the combination of both parameters was able to discriminate different prognostic subgroups. Moreover, hypoxic cancers were more often immunohistologically positive for tp53 protein and had a higher DNA index with the highest DNA index in tumors with both hypoxia and tp53 protein expression. These findings in summary support the theory that the tumor's microenvironment may influence the biologic behavior via hypoxia.

Adult↗

Predictive value of the tumor oxygenation by means of pO2 histography in patients with advanced head and neck cancer.

PURPOSE: The purpose of this analysis was to evaluate the potential of the tumor oxygenation by means of Eppendorf pO2 histography as a predictive test to select patients for treatment alternatives. PATIENTS AND METHODS: Pretreatment tumor pO2 histographies of locoregional lymph node metastases were assessed in 194 patients with squamous cell carcinoma of the head and neck. Included in the analysis were 134 patients who received a primary radio- or radiochemotherapy with a radiation dose of > or = 60 Gy, and who had no distant metastasis at beginning of the therapy. RESULTS: The Cox regression analysis revealed the fraction of pO2 values < or = 2.5 mm Hg (p = 0.004), age (p = 0.04) and radiotherapy/radiochemotherapy (p = 0.03) as significant independent prognostic factors for the survival. The positive and negative predictive values were calculated using different cut-off values of the fraction of pO2 values < or = 2.5 mm Hg and the survival status at 1 or 2 years after beginning of the therapy as endpoint. The highest positive and negative predictive values of all cut-off values were 0.50 and 0.41 at 1 year, and 0.81 and 0.26 at 2 years. CONCLUSIONS: Our data confirm the influence of the tumor oxygenation on the prognosis of patients with squamous cell carcinoma of the head and neck after radiotherapy. However, the calculated positive and negative predictive values suggest that the pO2 histography alone is not sufficient to be used as a predictive test to successfully select patients for treatment alternatives.

Adult↗

Tumor hypoxia and systemic levels of vascular endothelial growth factor (VEGF) in head and neck cancers.

BACKGROUND: Hypoxia is the most important stimulus for the up-regulation of vascular endothelial growth factor (VEGF), one of the key cytokines for angiogenesis. We have investigated the possible relationship between tumor hypoxia and systemic levels of VEGF. PATIENTS AND METHODS: 56 patients with head and neck cancers underwent measurement of tumor volume (pretreatment CT scans), tumor oxygenation (pO2 histography) and serum levels of VEGF. The hemoglobin level ranged from 9.1 to 16 g/dl. The absolute amount of hypoxic tumor (hypoxic tumor volume) was determined as the product of the absolute tumor volume and the relative frequency of hypoxic (< 5 mm Hg) measurements in the pO2 histography. RESULTS: The serum VEGF levels in the 56 head and neck cancer patients ranged from 102 to 1699 pg/ml (median 405 pg/ml, mean 527 +/- 396 pg/ml). Elevated serum-VEGF levels (> 700 pg/ml) were found in 14/56 patients (25%). Serum-levels of VEGF were significantly and independently correlated with hypoxic tumor volume (R2 = 0.63, p < 0.001), but also with total tumor volume, hemoglobin levels, platelet counts and tumor hypoxia. There was no correlation with T and N category, histological grading, and age. CONCLUSIONS: The strong and independent impact of the hypoxic tumor volume on systemic VEGF levels suggests that the absolute amount of hypoxia within a tumor represents the most important stimulus for up-regulation of angiogenesis. Anemia acts as a co-factor via worsening of tumor tissue oxygenation.

Adult↗

Life-threatening complications of hepatitis B virus-related polyarteritis nodosa developing despite interferon-alpha2b therapy: successful treatment with a combination of interferon, lamivudine, plasma exchanges and steroids.

Polyarteritis nodosa (PAN) is a rare vasculitis associated with hepatitis B virus (HBV) infection in a significant proportion of cases. When used to treat HBV-related PAN, immunosuppressive agents may enhance viral replication and relaspes are frequent. In recent years the use of antiviral drugs has been proposed. We report the case of a patient with HBV-related PAN who, despite 6 weeks of interferon-alpha2b (IFN-alpha2b) monotherapy, developed life-threatening complications with bowel perforation. He was thereafter successfully treated with a combination of IFN-alpha2b, lamivudine, plasma exchanges and short-term steroids. In contrast to IFN-alpha2b, lamivudine is effective in rapidly suppressing viral replication. This may be valuable in the treatment of HBV-related PAN by contributing to a faster diminution of circulating immune complex levels. This case report highlights the importance of aggressive combined therapy in patients with HBV-related PAN.

Adult↗

[Association between elevated serum VEGF and polarographically measured tumor hypoxia in head and neck carcinomas].

PURPOSE: Clinical investigation of a potential relationship between VEGF concentration in serum (sVEGF) and polarographically measured tumor oxygenation in patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: In 56 patients with SCCHN we estimated the classical tumor parameters, the sVEGF concentration (immunoassay) and the tumor oxygenation (Eppendorf pO2 histograph). The platelet count and the tumor volume were evaluated simultaneously. RESULTS: In a unifactorial analysis the total volume (132 cm3 vs. 38 cm3), the hypoxic subvolume (HSV = total volume multiplied with the relative frequency of values < or = 5 mm Hg/63 cm3 vs. 10 cm3) and the platelet count (380 10(9)/l vs. 271 10(9)/l) were significantly higher in the patient group with a sVEGF level > 707 pg/ml compared to the group with a sVEGF below this threshold. The multifactorial analysis confirmed significant effects for the hypoxic subvolume and the platelet count. Regarding hypoxic subvolume and sVEGF as continuous parameters a significantly positive correlation was found. This correlation remained somewhat weaker but significant after inclusion of the platelet count as covariate. CONCLUSION: On base of our data a clinical association between elevated sVEGF and polarographically measured tumor hypoxia could be confirmed. This was possible considering not only the relative grade of hypoxia but also the absolute amount of hypoxic regions. The VEGF released from platelets during blood clotting influences the sVEGF level essentially, however, the hypoxia effect was not completely deleted. Due to the platelet effect an estimation of sVEGF is not able to substitute polarographical measurement of tumor pO2. Therefore in an ongoing study we investigate whether VEGF values estimated in plasma are better correlated with the polarographically measured tumor pO2 than serum VEGF levels.

Adult↗