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Biomedical subjects

C Schmitz

Publications and source records attributed to C Schmitz.

At least 109 records · Page 6Linked to original sources

Improvement of heart-, lung-, and liver-performance during mechanical circulatory support by the Novacor-system.

OBJECTIVE: Since its clinical introduction, the Novacor left ventricular assist system (LVAS) has proved to be a reliable and safe method for bridging to cardiac transplantation. To find out whether univentricular assistance is sufficient in patients with severe global heart failure, multi organ monitoring using the COLD system was performed. METHODS: In seven patients (mean age 38.8 years), the wearable Novacor system N100 was implanted. Preoperatively, during the first 72 h thereafter and before heart transplantation right and left ventricular cardiac output, right ventricular ejection fraction, pulmonary-, intrathoracic-and total blood volume, extravascular lung water and excretory liver function were monitored by means of double indicator dilution technique with the COLD system. Conventional hemodynamic parameters have also been documented. RESULTS: During left ventricular assistance, both pulmonary and systemic arterial cardiac outputs increased significantly (Student's t-test, P < 0.05). Right ventricular ejection fraction rose from 17 to 26%, preoperatively elevated pulmonary and intrathoracic blood volumes and extravascular lung water fell significantly to normal ranges. Total blood volume remained constant, excretory liver function improved markedly. CONCLUSIONS: Pulmonary cardiac output improves due to the reduced right ventricular afterload by unloading the impaired left ventricle with the Novacor pump. The drop in pulmonary blood volume, intrathoracic blood volume and extravascular lung water also indicates a decrease of pulmonary congestion. Since total blood volume remains unchanged, a volume shift to the systemic circulation is suggested, resulting in an improved splanchnic perfusion as demonstrated by a better excretory liver function. In the absence of primary pulmonary hypertension, treatment of global heart failure with a left ventricular assist device is possible. The COLD system is a useful tool for managing this patient group during the postoperative period.

Adult↗

Resection of hypernephromas with vena caval or right atrial tumor extension using extracorporeal circulation and deep hypothermic circulatory arrest: a multidisciplinary approach.

OBJECTIVE: Among retroperitoneal tumors, renal cell carcinoma most often invades the retrohepatic inferior vena cava or the right atrium. Even in these cases, radical nephrectomy may be performed with curative intention. The aim of this retrospective study was to elucidate the impact of cardiopulmonary bypass and hypothermic circulatory arrest on surgical complications, primary mortality, and long-term survival. PATIENTS AND METHODS: From Jan. 1981 till Aug. 1996, 44 patients were operated upon for renal cell carcinoma with advanced vena caval extension. The patients were divided into two groups. In 19 cases (Cardiopulmonary Bypass Group), extracorporeal circulation and deep hypothermic circulatory arrest was used. The Conventional Technique Group comprised 25 patients who had radical nephrectomy, paraaortic lymphadenectomy and extirpation of the intracaval tumor thrombus applying common principles in vascular surgery. The median age was 59 years with a range from 42 to 78 years in the Cardiopulmonary Bypass Group, and 60 years, ranging from 22 to 72 years, in the Conventional Technique Group. In addition, both groups did not differ in gender, UICC TNMG staging classification, and perioperative risk factors. A review of the patient charts was done and surveys were sent to survivors or nearest of kin. Wilcoxon test and log-rank test were used as appropriate. RESULTS: A lower intraoperative complication rate was found in patients who had surgery using cardiopulmonary bypass. This was especially true with embolization of the tumor thrombus into the pulmonary arteries: 0.0% in Cardiopulmonary Bypass Group and 16.0% in Conventional Technique Group (P < 0.05). Severe hemorrhage occurred in 10.5% (Cardiopulmonary Bypass Group) and 16.0% (Conventional Technique Group). This translated into a significantly lower perioperative mortality in the Cardiopulmonary Bypass Group when compared to the Conventional Technique Group (5.6 and 16.0%, respectively). In spite of these results, differences in long-term survival did not reach statistical significance. But, a trend to superior long-term survival was apparent. The mean survival was 1289 +/- 278 days in the Cardiopulmonary Bypass Group and 746 +/- 166 days in the Conventional Technique Group. CONCLUSIONS: Due to acceptable long-term results, the resection of hypernephromas showing extensive vena caval invasion seems to be justified. The use of cardiopulmonary bypass and hypothermic circulatory arrest is able to decrease primary morbidity and mortality. However, the influence on long-term survival remains to be proven.

Adult↗

Platelet morphology in patients with mechanical circulatory support.

OBJECTIVE: Mechanical circulatory support is a therapy for patients with end stage cardiac insufficiency. The thromboembolic events are feared complications during support, due to the surface thrombogenicity of the implanted device. Activated blood platelets play a major role in this context. Consequently the platelet morphology of patients was investigated. METHODS: Platelets of eight patients were observed by means of scanning electron microscopy during the period of support with the Novacor left ventricular assist system N100. Blood was collected preoperatively and daily during the first week as well as weekly during the first 3 months. Samples were fixed with cacodylic-acid buffered glutaraldehyde. Platelet alterations were classified as non-activated, activated and aggregated, based on the so-called 'shape change' morphology. In addition, blood coagulation parameters were evaluated (e.g. activated partial thromboplastin time, prothrombin time, antithrombin III). RESULTS: Preoperatively, 15.0 +/- 4.6% (overall mean values) of activated platelets were found. Within the first postoperative week, the mean level of activated platelets increased to 32.8 +/- 8.0% (P < 0.05). Comparing short- (< 30 days; n = 4) vs. long-period (> 30 days; n = 4) support, a significant difference of activated platelets was evaluated (24.3 +/- 3.3% vs. 34.8 +/- 3.4%, P = 0.004). A correlation was found between the values of activated clotting time and activated platelets. Specific platelet deformations and damages appeared during support, which could not be found preoperatively. CONCLUSIONS: The platelet morphology showed alterations in all patients probably most strongly induced by the surface activation of the implanted device. These observations should be taken into consideration in management of postoperative anticoagulation therapy.

Adult↗

Surgical treatment of the Bland-White-Garland syndrome in early infancy: subclavian to coronary artery anastomosis via left anterolateral thoracotomy extended by a transverse sternotomy.

The case of a 6-week-old girl with left coronary artery originating from the pulmonary artery (Bland-White-Garland syndrome) is reported. Therapy consisted of a subclavian-coronary artery anastomosis via left anterolateral thoracotomy extended by transverse sternotomy. This approach allowed both the easy dissection of the left subclavian artery and the use of extracorporeal circulation while doing the anastomosis. Operation and postoperative course were uneventful. Angiography after one year revealed a patent anastomosis and a totally recovered left-ventricular function.

Coronary Artery Bypass↗

The influence of microgravity on repair of radiation-induced DNA damage in bacteria and human fibroblasts.

The influence of the space flight environment, above all microgravity, on the repair of radiation-induced DNA damage was examined during the Spacelab mission IML-2 as (1) rejoining of DNA strand breaks induced by X irradiation in cells of Escherichia coli B/r (120 Gy) and (2) in human fibroblasts (5 and 10 Gy); (3) induction of the SOS response after gamma irradiation (300 Gy) of cells of Escherichia coli PQ37; and (4) survival of spores of Bacillus subtilis HA 101 after UV irradiation (up to 340 J m(-2)). Cells were irradiated prior to the space mission and were kept frozen (E. coli and fibroblasts) until incubation for defined periods (up to 4.5 h) in orbit; thereafter they were frozen again for laboratory analysis. Germination and growth of spores of B. subtilis on membrane filters was initiated by humidification in orbit. Controls were performed in-flight (1g reference centrifuge) and on the ground (1g and 1.4g). We found no significant differences between the microgravity samples and the corresponding controls in the kinetics of DNA strand break rejoining and of the induction of the SOS response as well as in the survival curves (as proven by Student's t test, P < or = 0.1). These observations provide evidence that in the microgravity environment cells are able to repair radiation-induced DNA damage almost normally. The results suggest that a disturbance of cellular repair processes in the microgravity environment might not be the explanation for the reported synergism of radiation and microgravity.

Adult↗

Genetic polymorphism of methylenetetrahydrofolate reductase and myocardial infarction. A case-control study.

BACKGROUND: Elevated total plasma homocyst(e)ine (tHcy; the composite of homocysteine-derived moieties in their oxidized and reduced forms) levels are a risk factor for coronary heart disease, stroke, and venous thrombosis. tHcy plasma levels are influenced by folate, vitamins B6 and B12, as well as by hereditary factors. A point mutation (C677T) in the gene encoding methylenetetrahydrofolate reductase, an enzyme involved in homocysteine remethylation, has been reported to render the enzyme thermolabile and less active and has been associated with elevated tHcy in homozygous carriers (+/+ genotype) as well as with increased risk of premature cardiovascular disease. METHODS AND RESULTS: We investigated whether this mutation influences risk for myocardial infarction (MI) and plasma levels of tHcy and whether this effect may be modified by dietary folate intake in 190 MI cases and 188 control subjects from the Boston Area Health Study. Genotype frequencies were 37.8% for -/-, 47.8% for +/-, and 14.4% for +/+ in the control group and 50.0% for -/-, 34.7% for +/-, and 15.3% for +/+ in the case group. The relative risk for MI associated with the +/+ genotype (compared with +/- and -/-) was 1.1 (95% CI, 0.6 to 1.9; P = .8). Stratification by folate intake values above and below the median did not significantly alter these results. Plasma tHcy levels were 9.9 +/- 2.7 mumol/L in -/- individuals, 10.6 +/- 3.8 mumol/L in +/- individuals, and 9.1 +/- 2.3 mumol/L in +/+ individuals (Ptrend = NS; determined in 68 cases and 59 control subjects). CONCLUSIONS: Our data show that homozygosity for the C677T mutation in this largely white, middle-class US population is not associated with increased risk for MI, irrespective of folate intake. This suggests that this mutation does not represent a useful marker for increased cardiovascular risk in this and in similar populations.

Aged↗

DNA repair in microgravity: studies on bacteria and mammalian cells in the experiments REPAIR and KINETICS.

The impact of microgravity on cellular repair processes was tested in the space experiments REPAIR and KINETICS, which were performed during the IML-2 mission in the Biorack of ESA: (a) survival of spores of Bacillus subtilis HA101 after UV-irradiation (up to 340 J m-2) in the experiment REPAIR; (b) in the experiment KINETICS the kinetics of DNA repair in three different test systems: rejoining of X-ray-induced DNA strand breaks (B1) in cells of Escherichia coli B/r (120 Gy) and (B2) in human fibroblasts (5 and 10 Gy) as well as (B3) induction of the SOS response after gamma-irradiation (300 Gy) of cells of Escherichia coli PQ37. Cells were irradiated prior to the space mission and were kept in a non-metabolic state (metabolically inactive spores of B. subtilis on membrane filters, frozen cells of E. coli and human fibroblasts) until incubation in orbit. Germination and growth of B. subtilis were initiated by humidification, E. coli and fibroblasts were thawed up and incubated at 37 degrees C for defined repair periods (up to 4.5 h), thereafter they were frozen again for laboratory analysis. Relevant controls were performed in-flight (1 x g reference centrifuge) and on ground (1 x g and 1.4 x g) The results show no significant differences between the microgravity samples and the corresponding controls neither in the survival curves nor in the kinetics of DNA strand break rejoining and induction of the SOS response (proven by Student's t-test, 2 P = 0.05). These observations provide evidence that in the microgravity environment cells are able to repair radiation-induced DNA damage close to normality. The results suggest that a disturbance of cellular repair processes in the microgravity environment might not be the explanation for the reported synergism of radiation and microgravity.

Bacillus subtilis↗

In vitro testing of heart valve wear outside of the manufacturers laboratory--requirements and controversies.

BACKGROUND AND AIM OF THE STUDY: Currently, various national and international Standards regulate in vitro and in vivo testing as well as the clinical evaluation of heart valve prostheses. This study concentrates on a single aspect of these protocols: accelerated wear and fatigue testing. METHODS: The differences in the above Standards were appraised and an experimental study was designed to assess the validity of Standard testing conditions with respect to in vivo relevance. An instrumented BSCC tilting disc valve was tested in two different types of fatigue testers and in a separate study in a sheep model. RESULTS: By comparing the obtained results it could be clearly demonstrated that under the current Standard conditions (ISO, CEN, FDA) actual in vivo impact loading cannot be reproduced. Also, the two compared test devices, though operating under the same Standard conditions, generated totally different loading conditions on the test valve. CONCLUSIONS: Based on these findings it is suggested that the actual loading conditions of each valve type should be measured either in vivo in animal models or within a circulatory mock loop which provides physiologic loading conditions, and the test conditions for accelerated wear and fatigue testing should be modified accordingly. Cavitation effects which can be assumed to be associated with high frequency wear testing is another important issue which has to be addressed in future amendments to the Test Standards.

Animals↗

[Effect of a new bradycardic substance on the isolated rabbit heart].

Beside wall tension and contractility, heart rate is a major determinant of myocardial oxygen consumption. Therefore, a decrease in heart rate could prevent ischemia or reduce its consequences. We examined the effect of a new bradycardic agent of the benzazepinone-type (DK-AH 269) on eight isolated, saline-perfused rabbit hearts, bradycardia resulted from a specific blockade of i(f)-channels in sinus node cells. After control measurements (C), the substance was added in three increasing concentrations (D1: 10(-8) M, D2: 10(-7) M, D3: 10(-6) M). We observed a dose-dependent reduction in heart rate (C: 206 +/- 25, D1: 195 +/- 30, D2: 77 +/- 41, D3: 154 +/- 48/min). In the highest dosage, the duration of diastole was increased by 100%. To characterize systolic function, we measured stroke volume (SV), peak left ventricular pressure (LVPmax) and its first derivative (dP/dtmax). Aortic flow was slightly decreased whereas SV increased to 108% of control after initial reduction at the two lower dosages. LVPmax remained unchanged, and dP/dtmax was dose-dependently reduced to 91, 81, and 70% of control (C: 1885 +/- 376, D1: 1721 +/- 525, D2: 1526 +/- 504, D3: 1327 +/- 337 mm Hg/s); dP/dtmin as a measure of early relaxation was also reduced. The coronary flow per beat did not change compared with control in the presence of the two lower doses of DK-AH 269, but was significantly increased with the highest dose (C: 0.29 +/- 0.06, D1: 0.28 +/- 0.07, D2: 0.29 +/- 0.09, D3: 0.34 +/- 0.11 ml). The myocardial oxygen demand was dose-dependently decreased (C: 10.4 +/- 2.5, D1: 9.6 +/- 2.5, D2: 8.8 +/- 2.6, D3: 7.9 +/- 2.4 ml/min/100 g). The relation between subendocardial and subepicardial flow, assessed with colored microspheres, exhibited no changes in the presence of the highest dose of DK-AH 269 (C: 1.28 +/- 0.09, D3: 1.27 +/- 0.08). DK-AH 269 reduced heart rate in isolated rabbit hearts and increased the duration of diastole. Whereas systolic function was primarily left unchanged, coronary flow per beat and oxygen consumption were decreased. According to our results, this new bradycardic agent could be useful in treating coronary heart disease.

Animals↗

Experience with the Novacor left ventricular assist system as a bridge to cardiac transplantation, including the new wearable system.

The three components of the Novacor left ventricular assist system, compact controller, battery, and back-up battery, have been miniaturized in the development of the wearable system. Therefore patients can be fully mobilized receiving mechanical circulatory support while awaiting heart transplantation. Between February 1992 and April 1994 a total of eight patients with decompensated heart failure (6 dilated cardiomyopathy, 1 acute myocarditis, 1 ischemic cardiomyopathy) were treated with the Novacor left ventricular assist systems. In the most recent four cases the wearable system (N100P) was used. Patients' ages ranged from 17 to 49 years. In five patients severe failure of the right side of the heart was present at the time of implantation. Hemodynamic stabilization was achieved in all patients during the 2 to 122 days (mean 30.8 +/- 42.5 days) of support. The following parameters were measured on average before and 24 hours after implantation of the left ventricular assist system: mean arterial pressure 70 +/- 11 versus 87 +/- 13 mm Hg (p < 0.05), cardiac index 1.71 +/- 0.42 versus 3.23 +/- 0.74 L/min/m2 (p < 0.05), pulmonary capillary wedge pressure 27.1 +/- 4.4 versus 9.9 +/- 5.2 mm Hg (p < 0.01), mean pulmonary pressure 41 +/- 9 versus 27 +/- 6 mm Hg (p < 0.05), and right ventricular ejection fraction 16.7% +/- 10.3% versus 22.0% +/- 11.6% (not significant). Patients who received the wearable system were capable of managing their own power supply during the bridging period and were able to walk to the hospital park and shopping area. One patient had a serious pulmonary infection, which was treated successfully, and two patients had a cerebrovascular accident, which resolved in one and resulted in a minor residual deficit in the other. All eight patients received a heart transplant. One patient died early after transplantation and seven patients are alive and well. In summary, the wearable Novacor left ventricular assist system provides major advantages regarding quality of life of patients during mechanical circulatory support. However, there is a remaining risk of thromboembolism despite anticoagulation therapy.

Adolescent↗

Heavy ion induced DNA double strand breaks in cells of E. coli.

Vegetative cells of E. coli differing in their radiosensitivity have been used in heavy ion irradiation experiment. Besides inactivation measurements also the induction of DNA double strand breaks (DSB) have been measured using the method of pulse-field gel electrophoresis. This method allows to separate linear DNA with length up to 8 Mio base pairs. After irradiation with heavy ions we find a higher amount of low molecular weight fragments when compared to sparsely ionizing radiation. This agrees with the idea that heavy ions as a structured radiation have a high probability to induce more than one strand break in a DNA molecule if the particle hits the DNA. The amount of intact DNA remaining in the agarose plugs decreases exponentially for increasing radiation doses or particle fluences. From these curves cross sections for the induction of DSB after heavy ion irradiation have been determined. These results will be discussed in comparison to the results for cell survival.

Argon↗

Effects of heavy ions on inactivation and DNA double strand breaks in Deinococcus radiodurans R1.

Inactivation and double strand break (dsb) induction after heavy ion irradiation were studied in stationary phase cells of the highly radiation resistant bacterium Deinococcus radiodurans R1. There is evidence that the radiation sensitivity of this bacterium is nearly independent on energy in the range of up to 15 MeV/u for lighter ions (Ar). The responses to dsb induction for charged particles show direct relationship between increasing radiation dose and residual intact DNA.

Argon↗

New morphologic aspects of explanted Hancock Extracorporeal pericardial bioprostheses.

Between 1981 and 1987 a total of 479 Hancock Extracorporeal bovine pericardial bioprostheses were implanted in 458 patients. During the time period from 1990 to 1993, 21 valves, 15 in the aortic and six in the mitral position, had to be removed 72 to 109 months after implantation. The mean age of these patients at the time of implantation was 49.7 +/- 10.5 years. All 21 removed as well as one unimplanted bioprosthesis were morphologically investigated. Visual examination, radiography, histology and ultrastructural observations were performed using scanning and transmission electron microscopy. In addition, clinical data were correlated to morphological findings. All valves failed due to cusp tears originating at the stent posts. Calcification was minimal in five valves, moderate in 10, and severe in five valves. Only one valve showed no mineralization at all. The late morphologic changes were associated with thickening of valve leaflets, tissue delamination, calcification, degeneration of collageneous network, and extensive insudation of plasma proteins and lipids. The present findings suggest that denatured collagen molecules may be capable of inducing immune response.

Adult↗