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Biomedical subjects

F Christ

Publications and source records attributed to F Christ.

At least 19 recordsLinked to original sources
PubMed2005

[Microcirculatory monitoring of sepsis].

Microcirculatory dysfunctions play a central role in the pathophysiology of sepsis and shock. Modern methods enable microvascular monitoring in man and offer the possibility to test the effect of novel therapeutical strategies for sepsis. Furthermore, these techniques may be future tools for the monitoring of critically ill patients. In this review, we will describe four microvascular monitoring devices and give an overview of the microcirculatory changes observed during the course of sepsis. Laser Doppler fluxmetry is an easy to use noninvasive technique to measure tissue perfusion enabling monitoring of the effect of different catecholamines on the gastric perfusion during sepsis. Increased microvascular permeability and altered blood flow in septic patients can be quantified by venous congestion plethysmography. Alterations in sublingual microvascular blood flow are detected by intravital microscopy in septic patients and were identified as an outcome predictor. Furthermore, the role of gastrointestinal pCO2-tonometry for microcirculatory monitoring of the perfusion of splanchnic organs during sepsis is discussed. The true clinical value of these techniques has yet to be established and will depend on larger clinical trials showing an impact on diagnostics and patient management.

Humans↗
PubMed2004

[Pre-clinical management of shock patients].

The preclinical diagnosis of shock is still based on the patient's history, the physical examination, the injury pattern and a few hemodynamic parameters available in the emergency set-up. The clinical picture is characterised by hypotension and tachycardia, tachypnoe and dyspnoea as well as cerebral impairment. Results from recent clinical trials indicate, that a adapted and specific therapeutic approach for the various shock forms is necessary. In case of traumatic hypovolemic-hemorrhagic shock it is of particular relevance if penetrating trauma and/or uncontrolled bleeding exists. Under these conditions an immediate definite surgical treatment is required ("scoop and run") and a moderate hypotension should be tolerated. ("treat and run"). Fluid substitution and therapy with catecholamines should be used conservatively. In all other forms of shock the treatment approach can and should be more aggressive in order to improve microvascular perfusion as early as possible. Besides adequate fluid resuscitation in a combination of crystalloid and colloid solutions catecholamines and-under specific circumstances-also vasopressin should be used. Of utmost importance in the pre-clinical management of patients in shock is the optimal selection of the centre that the patient is referred to in order to establish the fastest and best possible definite treatment for the patient.

Catecholamines↗
PubMed2002

Influence of different cuff inflation protocols on capillary filtration capacity in human calves -- a congestion plethysmography study.

It has been suggested that venous congestion plethysmography (VCP) substantially underestimates microvascular permeability by activation of a veni-arteriolar constrictor mechanism, even when using small (< 25 mmHg) congestion pressure steps. We studied human lower limbs of 18 young healthy volunteers to test whether the congestion pressure step size of the VCP protocol has an influence on the values of the capillary filtration capacity (CFC) and isovolumetric venous pressure (P(vi)). Two different dual stage VCP pressure step protocols, with 3 and 10 mmHg steps, were used in randomised order and separated by a transient reduction in congestion pressure. Since lymph flow is known to increase after venous congestion, we also looked to see if changes in the estimated lymph flow (J(v)L) occur as a result of these VCP protocols. The measured CFC (median [25th; 75th percentile]) was 2.6 [2.5; 3.2] x 10(-3) ml (100 ml)(-1) min(-1) mmHg(-1) with the 3 mmHg pressure step protocol, which was not different from the value of 2.9 [2.7; 3.4] x 10(-3) ml (100 ml)(-1) min(-1) mmHg(-1) obtained with 10 mmHg pressure steps. However, when either of these step sizes was applied after a transient venous decongestion, significantly higher values of CFC, 4.0 [3.4; 4.1] x 10(-3) and 3.5 [3.1; 4.5] x 10(-3) ml (100 ml)(-1) min(-1) mmHg(-1), respectively, were obtained (P < 0.05). The assessment of P(vi) was also independent of the pressure protocol (10 mmHg: 8.0 [5.7; 13.2] mmHg and 3 mmHg: 15.7 [12.5; 18.5] mmHg), but when P(vi) was measured after the transient deflation, significantly higher values were found with both 10 and 3 mmHg steps (24.1 [20.9; 27.3] and 30.4 [28.9; 30.9] mmHg, respectively; P < 0.01). The transient pressure reduction was associated with a rise in estimated J(v)L from 0.04 [0.03; 0.05] to 0.12 [0.08; 0.18] and 0.04 [0.04; 0.05] to 0.09 [0.07; 0.10] ml (100 ml)(-1) min(-1), respectively (P < 0.01). The first stage data from these protocols shows that the value of CFC is not influenced by the size of the cumulative venous pressure steps, providing they are of 10 mmHg or less. The data also show that J(v)L can be estimated with small step VCP protocols. We hypothesise that the sudden reduction in cuff pressure after venous congestion is associated with a temporary upregulation of lymph flow. As the congestion pressure is raised again, there is a modulation of the enhanced lymph flow, such that the resulting CFC slope appears greater than that obtained in the first stage of the protocol.

Adult↗
PubMed2002

Cryopreservation of reduced cytochrome C for determination of N-formyl-methionyl-leucyl-phenylalanine-stimulated superoxide anion production in human whole blood.

Various methods are available for measuring the production of reactive oxygen species by phagocytes, but they are limited in their use by the need for their immediate application, cell isolation and of cell-activation by unphysiological stimuli. In addition, after measurement of reactive oxygen metabolites using oxidizing agents, the reduced compounds formed have to be determined during or immediately after their formation. In the present study, an improved cytochrome C assay was investigated which allowed measurements of superoxide anions in whole blood samples following activation of phagocytes by physiological stimuli such as the bacterial tripeptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). The fMLP-stimulated production of superoxide anion (O(2)(-)) showed a sigmoidal-shaped fMLP dose-response curve, and constant O(2)(-) production rates (nmol.1(-1)x10(6) granulocytes) could be determined reliably up to a blood granulocyte concentration of 1 x 10(4) x microl(-1). To allow the determination of reduced cytochrome C later after its formation, the effect of long-term storage at -20 degrees C on the stability of reduced cytochrome C was tested up to 16 weeks. The results obtained show that the determination of reduced cytochrome C in whole blood represents a simple and reliable method. Most importantly, O(2)(-)-reduced cytochrome C can be frozen and stored without any alterations, at least up to 2 weeks. Thus the method seems to be superior to other methods of detection, especially when the experimental conditions do not allow immediate spectrophotometry (e.g. mountain medicine, space medicine). Under such conditions the present assay would allow reliable measurement of reduced cytochrome C, even after weeks of cryopreservation.

Cell Separation↗
PubMed2002

[Orthogonal polarization spectral imaging--a new clinical method for monitoring of microcirculation].

The orthogonal polarization spectral (OPS) imaging technology is a new non-invasive method to directly visualize multiple conditions of the microcirculation which has several clinical applications in humans. Quantitative measurement of the diameter of vessels, the velocity of red blood cells and functional capillary density (FCD) can be made. Activation of leukocytes can be monitored and also quantified. A transdermal approach can be used in premature babies and neonates to view the microcirculation and has also been used experimentally to determine haemoglobin levels. The application to various surfaces and solid organs allows a variety of pathophysiologies and phases to be examined.

Blood Flow Velocity↗
PubMed2002

Microvascular changes during anesthesia: sevoflurane compared with propofol.

BACKGROUND: We have developed a non-invasive computer-assisted venous congestion plethysmograph to measure the microvascular parameters in the lower limbs. This enables the assessment of microvascular changes following the induction of standardized anesthesia with either sevoflurane or propofol. METHODS: In a prospective randomized trial we measured the capillary filtration coefficient (CFC), isovolumetric venous pressure (Pvi), an index of the balance of Starling forces, and limb blood flow 24 h preoperatively, immediately after induction of anesthesia and on the 1st and 2nd postoperative day. Anesthesia was maintained with either 1.0% sevoflurane and 5 microg/kg/h remifentanil or propofol (3 mg/kg/h), and 5 microg/kg/h remifentanil in 20 female patients undergoing breast surgery. RESULTS: Preoperatively we found no significant differences between the mean CFC values of the sevoflurane group (3.7+/-0.3 ml/min 100 ml tissue/mmHg x 10-3=CFCU) and the propofol group (3.5+/-0.3 CFCU). In the sevoflurane group CFC decreased significantly to 2.9+/-0.2 CFCU, whereas it was unchanged in the propofol group. Both groups revealed a significant reduction in Pvi during steady-state anesthesia. Limb blood flow remained unchanged. There was an overall significant positive correlation between the perioperative fluid substitution and the difference between the preoperative and intraoperative CFC values (r = 0.64, P<0.01). CONCLUSION: The decreased CFC in response to sevoflurane may result in less extravasation of fluids into the interstitial space, thereby reducing intraoperative fluid requirements. These data suggest that sevoflurane may be the preferred anesthetic agent in subjects susceptible to large intraoperative fluid shifts.

Adult↗
PubMed2002

Effects of confinement (110 and 240 days) on neuroendocrine stress response and changes of immune cells in men.

The aim of the study was to evaluate the effects of long-term confinement on stress-permissive neuroendocrine and immune responses in humans. Two groups of four male subjects were confined 240 days (group 240) or 110 days (group 110) in two space modules of 100 or 200 m3, respectively. During confinement, none of the volunteers developed psychic stress as could be examined and verified by a current stress test. However, in group 240 but not in group 110, the diurnal rhythm of cortisol secretion was slightly depressed and the urine excretion of norepinephrine significantly increased. The innate part of the immune system became activated as seen by a rise in the number of circulating granulocytes and the enhanced expression of beta2-integrins. In contrast, the ratio of T-helper to T-suppressor cells decreased. All these effects, observed during confinement, were even more pronounced in both groups when values of endocrinological and immunological parameters were compared between before and 1 wk after the end of the confinement period. Hence, return to normal life exerts pronounced effects to a much higher degree, irrespective of how long or under which conditions individuals were confined. Because the delayed-type hypersensitivity skin reaction against recall antigens remained unaffected, it is to be presumed that confinement appears to induce distinct sympathoadrenergic activation and immunological changes but no clinically relevant immunosuppression.

Adult↗
PubMed2001

[Prevalence and clinical significance of computerized tomography verified idiopathic calcinosis of the basal ganglia].

With increasing CT examinations of the cerebrum, the discovery of basal ganglia calcification becomes more frequent. In order to correlate these calcifications to the symptoms believed to be accompanied with Fahr's disease 2318 cranial CT scans were examined. There was an overall incidence of basal ganglia calcification of 12.5%. The most frequent location was the globus pallidus (96.4%). In the examined population there was no correlation found between the calcifications and symptoms having been described with striopallidentate calcifications.

Aged↗
PubMed2001

Simulated microgravity, psychic stress, and immune cells in men: observations during 120-day 6 degrees HDT.

Because 6 degrees head-down tilt (HDT) is an established method to mimic low gravity on earth, the aim of the present study was to determine the effects of 120-day HDT on psychic stress and peripheral blood immune cells in six healthy male volunteers. Psychological state was assessed by a current stress test, and cortisol was measured in saliva. During HDT, all volunteers developed psychic stress, and the diurnal rhythm of cortisol secretion was significantly altered. In addition, urine excretion of dopamine and norepinephrine increased. The innate part of the immune response was activated, as evidenced by the increase in the expression of beta(2)-integrins on polymorphonuclear leukocytes and a rise in the number of circulating natural killer (NK) cell lymphocytes. The ratio of T-helper to T-cytotoxic and T-suppressor cells decreased, whereas no changes in T and B lymphocytes were observed. Plasma levels of interleukin-6 increased significantly and returned to basal levels after the end of the HDT period. Thus 6 degrees HDT appears to be a valid model to induce psychic stress and neuroendocrine-related changes in the immune system, changes that might also be encountered by astronauts and cosmonauts during long-duration spaceflights.

Adult↗
PubMed2001

Changes in microvascular fluid filtration capacity during 120 days of 6 degrees head-down tilt.

We used venous congestion strain gauge plethysmography (VCP) to measure the changes in fluid filtration capacity (K(f)), isovolumetric venous pressure (Pv(i)), and blood flow in six volunteers before, on the 118th day (D118) of head-down tilt (HDT), and 2 days after remobilization (Post). We hypothesized that 120 days of HDT cause significant micro- and macrovascular changes. We observed a significant increase in K(f) from 3.6 +/- 0.4 x 10(-3) to 5.7 +/- 0.9 x 10(-3) ml. min(-1). 100 ml(-1). mmHg(-1) (+51.4%; P < 0.003), which returned to pretilt values (4.0 + 0.4 x 10(-3) ml. min(-1). 100 ml(-1). mmHg(-1)) after remobilization. Similarly, Pv(i) increased from 13.4 +/- 2.1 mmHg to 28.9 +/- 2.8 mmHg (+105.8%; P < 0.001) at D118 and was not significantly different at Post (12.4 +/- 2.6 mmHg). Blood flow decreased significantly from 2.3 +/- 0.3 to 1.3 +/- 0.2 ml. min(-1). 100 ml tissue(-1) at D118 and was found elevated to 3.4 +/- 0.7 ml. min(-1). 100 ml tissue(-1) at Post. We believe that the increased K(f) is caused by a higher microvascular water permeability. Because this may result in edema formation, it could contribute to the alterations in fluid homeostasis after exposure to microgravity.

Adult↗
PubMed2000

A model for the PI-SceIxDNA complex based on multiple base and phosphate backbone-specific photocross-links.

We have synthesized different oligodeoxynucleotides carrying, in single positions of the >36 bp recognition site of PI-SceI, photoreactive base analogues (5-iododeoxypyrimidines) or phosphate modifications (p-azidophenacylphosphorothioates) and used them in photocross-linking experiments with PI-SceI to probe the protein-DNA interface of the specific complex between the homing endonuclease PI-SceI and its DNA substrate. One base-specific and several backbone-specific cross-links were analyzed in detail: the cross-linking positions were identified by Edman degradation of isolated cross-linked peptidexoligodeoxynucleotide adducts and confirmed by site-directed mutagenesis. Based on these results and the crystal structure of PI-SceI, a model for the structure of the PI-SceIxDNA complex is proposed.

Base Pairing↗
PubMed2000

Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1.

The capacity of the adult brain and spinal cord to repair lesions by axonal regeneration or compensatory fibre growth is extremely limited. A monoclonal antibody (IN-1) raised against NI-220/250, a myelin protein that is a potent inhibitor of neurite growth, promoted axonal regeneration and compensatory plasticity following lesions of the central nervous system (CNS) in adult rats. Here we report the cloning of nogo A, the rat complementary DNA encoding NI-220/250. The nogo gene encodes at least three major protein products (Nogo-A, -B and -C). Recombinant Nogo-A is recognized by monoclonal antibody IN-1, and it inhibits neurite outgrowth from dorsal root ganglia and spreading of 3T3 fibroblasts in an IN-1-sensitive manner. Antibodies against Nogo-A stain CNS myelin and oligodendrocytes and allow dorsal root ganglion neurites to grow on CNS myelin and into optic nerve explants. These data show that Nogo-A is a potent inhibitor of neurite growth and an IN-1 antigen produced by oligodendrocytes, and may allow the generation of new reagents to enhance CNS regeneration and plasticity.

3T3 Cells↗
PubMed2000

[Emergency medicine online course--integrating into curriculum of computer-based training].

Emergency medicine is characterized by rapid decision making to help patients in life-threatening situations. Teaching these skills requires a high level of interaction between medical students and the lecturer. We designed, implemented, and evaluated a generic computer-based training (CBT) system to provide a more active way of learning emergency medicine. The content of the training program is adapted to the knowledge of third year medical students and is focused on basic skills and real-world problems. The teacher presents the case with authentic video sequences and slides. The cases are classified into four groups: heart (e.g., myocardial infarction), respiration (e.g., asthma bronchiale), trauma (e.g., car accident), and loss of consciousness (e.g., coma). Within a realistic time frame, the students have to answer free text and multiple choice questions on a work-station. All answers given by the students are processed anonymously by the CBT system via a central server and displayed on a large video screen, thus enabling a detailed discussion without intimidation of individual students. This interactive technique allows for immediate feedback from the lecturer based on the specific knowledge of his group and his own experience. The IT concept, which is scalable to many subjects, is based on state of the art internet technology and therefore suitable for teleteaching. A major design objective for the program was a self-explaining and robust user interface. The system has been in routine use since 1998. We designed an evaluation form consisting of 21 items focused on subjective rating of learning success, acceptance of CBT, and technical feasibility. We analyzed forms from 138 students and found high scores for acceptance and learning success (median 5 on a 6-point scale). user problems with the program were denied (median 1 on a 6-point scale). Computer-based training with Internet technology can provide a successful method for interactive teaching of emergency medicine and is well accepted by students.

Computer Graphics↗
PubMed2000

Description and validation of a novel liquid metal-free device for venous congestion plethysmography.

We present a newly developed electromechanical sensor with automated calibration for strain-gauge plethysmography (filtrass) and compare it to a conventional mercury-in-Silastic strain-gauge plethysmograph (MSG). Fluid filtration capacity (K(f)) and isovolumetric venous pressure (Piv) of the limb were assessed noninvasively with both devices in 29 healthy volunteers. We found significantly higher K(f) and Piv values with MSG [4.6 +/- 2.0 x 10(-3) ml. min(-1). mmHg(-1). 100 ml tissue(-1) (K(f) units; K(f)U) and 21.2 +/- 8.1 mmHg for Pvi], than with filtrass, giving values of 3.1 +/- 0.8 K(f)U and 15.1 +/- 7.1 mmHg. Because K(f) and Piv are profoundly influenced by the calibration, we investigated the quality of the calibration signal and its impact on the obtained values. We could show that the reproducibility of repeated calibrations was higher with filtrass (58% lower mean +/- SD). The data were grouped according to the quality of calibration, and we found no significant difference in K(f) and Piv between filtrass (3.0 +/- 0.7 K(f)U and 15.9 +/- 6.9 mmHg, respectively) and MSG with good calibration signal (3.3 +/- 0. 8 K(f)U and 18.6 +/- 7.1 mmHg, respectively; no significant difference). However, we obtained significantly higher MSG values (5. 6 +/- 2.0 K(f)U and 23.1 +/- 8.4 mmHg, respectively; P < 0.001) in the group with a bad calibration signal. We suggest that the filtrass sensor, which performs an automatic, standardized calibration procedure and shows a linear signal response to stretch, gives highly reproducible and reliable results and thus is more suitable for routine application.

Adult↗
PubMed1999

The monomeric homing endonuclease PI-SceI has two catalytic centres for cleavage of the two strands of its DNA substrate.

The monomeric homing endonuclease PI-SceI cleaves the two strands of its DNA substrate in a concerted manner, which raises the question of whether this enzyme harbours one or two catalytic centres. If PI-SceI has only one catalytic centre, one would expect that cross-linking enzyme and substrate should prevent reorientation of the enzyme required to perform the second cut after having made the first cut: PI-SceI, however, when cross-linked to its substrate, is able to cleave both DNA strands. If PI-SceI has two catalytic centres, one would expect that it should be possible to inactivate one catalytic centre by mutation and obtain a variant with preference for a substrate nicked in one strand; such variants have been found. The structural homology between the catalytic domain of PI-SceI having a pseudo 2-fold symmetry, and I-CreI, a homodimeric homing endonuclease, suggests that in PI-SceI active site I, which attacks the top strand, comprises Asp218, Asp229 and Lys403, while Asp326, Thr341 and Lys301 make up active site II, which cleaves the bottom strand. Cleavage experiments with modified oligodeoxynucleotides and metal ion mapping experiments demonstrate that PI-SceI interacts differently with the two strands at the cleavage position, supporting a model of two catalytic centres.

Amino Acid Sequence↗