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Biomedical subjects

T Koch

Publications and source records attributed to T Koch.

At least 73 records · Page 4Linked to original sources

[Definition of shock types].

Definitions of shock types. Hypovolaemic shock is a state of insufficient perfusion of vital organs with consecutive imbalance of oxygen supply and demand due to an intravascular volume deficiency with critically impaired cardiac preload. Subtypes are haemorrhagic shock, hypovolaemic shock in the narrow sense, traumatic-haemorrhagic shock and traumatic-hypovolaemic shock. Cardiac shock is caused by a primary critical cardiac pump failure with consecutive inadequate oxygen supply of the organism. Anaphylactic shock is an acute failure of blood volume distribution (distributive shock) and caused by IgE-dependent, type-I-allergic, classical hypersensibility, or a physically, chemically, or osmotically induced IgE-independent anaphylactoid hypersensibility. The septic shock is a sepsis-induced distribution failure of the circulating blood volume in the sense of a distributive shock. The neurogenic shock is a distributive shock induced by generalized and extensive vasodilatation with consecutive hypovolaemia due to an imbalance of sympathetic and parasympathetic regulation of vascular smooth muscles.

Anaphylaxis↗

Adaptations to biotic and abiotic stress: Macaranga-ant plants optimize investment in biotic defence.

Obligate ant plants (myrmecophytes) in the genus Macaranga produce energy- and nutrient-rich food bodies (FBs) to nourish mutualistic ants which live inside the plants. These defend their host against biotic stress caused by herbivores and pathogens. Facultative, 'myrmecophilic' interactions are based on the provision of FBs and/or extrafloral nectar (EFN) to defending insects that are attracted from the vicinity. FB production by the myrmecophyte, M. triloba, was limited by soil nutrient content under field conditions and was regulated according to the presence or absence of an ant colony. However, increased FB production promoted growth of the ant colonies living in the plants. Ant colony size is an important defensive trait and is negatively correlated to a plant's leaf damage. Similar regulatory patterns occurred in the EFN production of the myrmecophilic M. tanarius. Nectar accumulation resulting from the absence of consumers strongly decreased nectar flow, which increased again when consumers had access to the plant. EFN flow could be induced via the octadecanoid pathway. Leaf damage increased levels of endogenous jasmonic acid (JA), and both leaf damage and exogenous JA application increased EFN flow. Higher numbers of nectary visiting insects and lower numbers of herbivores were present on JA-treated plants. In the long run, this decreased leaf damage significantly. Ant food production is controlled by different regulatory mechanisms which ensure that costs are only incurred when counterbalanced by defensive effects of mutualistic insects.

Adaptation, Physiological↗

Perfluorohexane attenuates proinflammatory and procoagulatory response of activated monocytes and alveolar macrophages.

BACKGROUND: A number of studies have demonstrated the effectiveness of liquid ventilation with perfluorocarbons in improving pulmonary function in acute respiratory distress syndrome. Although it is known that perfluorocarbon-associated gas exchange facilitates lung mechanics and oxygenation, the complete mechanism by which perfluorocarbons exert their beneficial effects in acute lung injury still remains unclear. Possibly, an influence of perfluorocarbons on proinflammatory and procoagulant features of monocytic cells present in the alveolar space, such as alveolar macrophages (AMs), may be involved. Therefore, we examined in an in vitro model the effects of perfluorocarbon on both activated mononuclear blood cells (MBCs) and AMs by monitoring the expression of interleukin (IL)-1 beta, tumor necrosis factor (TNF)alpha, and tissue factor (TF). METHODS: Mononuclear blood cells, obtained from peripheral blood of healthy volunteers, or AMs from diagnostic bronchoalveolar lavage were stimulated by incubation with lipopolysaccharide in the presence of different amounts of perfluorohexane, which was devoid of cytotoxicity. RESULTS: Using both video-enhanced contrast and electron microscopy, the authors observed that perfluorohexane droplets were phagocytosed by activated monocytes as well as by in vitro--cultured AMs within 1--3 h. After lipopolysaccharide stimulation of monocytes or AMs, we observed a down-regulation of TF mRNA and a significant inhibition (P < 0.05) of cellular TF antigen by perfluorohexane. In addition, the concentration of both IL-1 beta and TNF alpha in the supernatant of lipopolysaccharide-stimulated MBC was significantly decreased (P < 0.01) by perfluorohexane compared with controls without perfluorohexane. By preincubation of lipopolysaccharide-containing medium with perfluorohexane, the authors could exclude that the inhibitory effect of perfluorohexane was caused by binding or sequestering limited amounts of lipopolysaccharide. CONCLUSION: Taken together, our results demonstrate an interference of perfluorohexane with the expression of the procoagulant protein TF on monocytes and AMs as well as with the release of proinflammatory cytokines by MBCs. These effects may contribute to the protective role of liquid ventilation with perfluorocarbons in injuries associated with local activation of inflammatory processes.

Enzyme-Linked Immunosorbent Assay↗

N-acetylcysteine reduces respiratory burst but augments neutrophil phagocytosis in intensive care unit patients.

OBJECTIVE: The antioxidant N-acetylcysteine (NAC) has been shown to attenuate septic tissue injury. To evaluate whether NAC affects host defense mechanisms in critically ill patients, thus predisposing to increased risk of infection, the current study focuses on neutrophil phagocytotic and burst activity after treatment with NAC. DESIGN: Prospective, randomized, clinical trial. SETTING: Twelve-bed operative intensive care unit in a university hospital. PATIENTS: Thirty patients diagnosed with sepsis/systemic inflammatory response syndrome, or multiple trauma. INTERVENTIONS: Patients were randomly assigned to receive either NAC (n = 15) for 4 days in increasing dosages (day 1: 6 g; day 2: 12 g; days 3 and 4: 18 g) or a mucolytic basis dosage of NAC (3 x 300 mg/day [control]; n = 15), respectively. MEASUREMENTS AND MAIN RESULTS: Blood samples were taken before NAC high-dose infusion (day 1), after increasing doses of NAC (days 3 and 5) and 4 days after the last high-dose treatment (day 8). Neutrophil oxidative burst activity after stimulation with Escherichia coli and polymorphonuclear phagocytosis were determined in a flow cytometric assay. Baseline values of polymorphonuclear functions were comparable in both groups. NAC high-dose treatment resulted in a significantly improved phagocytosis activity compared with control patients. In contrast to this, polymorphonuclear burst activity was significantly reduced in the NAC high-dose treated group on day 3. CONCLUSION: These findings suggest that infusion of NAC in high doses affects granulocyte functions in critically ill patients. Antimicrobial host defense requires the effective sequence of cell adhesion, phagocytosis, and bactericidal respiratory burst. The enhanced phagocytotic activity might be a compensatory mechanism in states of impaired respiratory burst to maintain tissue sterility. For certain mechanisms of disease, the effects observed might be favorable (e.g., ischemia/reperfusion, endothelial cell activation), for others (infection) this might be detrimental.

APACHE↗

Ion channel-forming alamethicin is a potent elicitor of volatile biosynthesis and tendril coiling. Cross talk between jasmonate and salicylate signaling in lima bean.

Alamethicin (ALA), a voltage-gated, ion channel-forming peptide mixture from Trichoderma viride, is a potent elicitor of the biosynthesis of volatile compounds in lima bean (Phaseolus lunatus). Unlike elicitation with jasmonic acid or herbivore damage, the blend of substances emitted comprises only the two homoterpenes, 4,11-dimethylnona-1,3,7-triene and 4,8,12-trimethyltrideca-1,3,7,11-tetraene, and methyl salicylate. Inhibition of octadecanoid signaling by aristolochic acid and phenidone as well as mass spectrometric analysis of endogenous jasmonate demonstrate that ALA induces the biosynthesis of volatile compounds principally via the octadecanoid-signaling pathway (20-fold increase of jasmonic acid). ALA also up-regulates salicylate biosynthesis, and the time course of the production of endogenous salicylate correlates well with the appearance of the methyl ester in the gas phase. The massive up-regulation of the SA-pathway (90-fold) interferes with steps in the biosynthetic pathway downstream of 12-oxophytodienoic acid and thereby reduces the pattern of emitted volatiles to compounds previously shown to be induced by early octadecanoids. ALA also induces tendril coiling in various species like Pisum, Lathyrus, and Bryonia, but the response appears to be independent from octadecanoid biosynthesis, because inhibitors of lipoxygenase and phospholipase A(2) do not prevent the coiling reaction.

Alamethicin↗

Disability and difference: balancing social and physical constructions.

The world of disability theory is currently divided between those who insist it reflects a physical fact affecting life quality and those who believe disability is defined by social prejudice. Despite a dialogue spanning bioethical, medical and social scientific literatures the differences between opposing views remains persistent. The result is similar to a figure-ground paradox in which one can see only part of a picture at any moment. This paper attempts to find areas of commonality between the opposing camps, and thus to rearrange the figures of the paradox at a fundamental level. The purpose is first to identify areas in which common ground can be achieved, and secondarily, to clarify the areas in which disagreement continues. While a general and unified theory of physical difference/disability is beyond the scope of this paper the result may advance that general goal.

Bioethics↗

Volume replacement in critically ill patients with acute renal failure.

Maintenance and restoration of intravascular volume are essential tasks of critical care management to achieve sufficient organ function and to avoid multiple organ failure in critically ill patients. Inadequate intravascular volume followed by impaired renal perfusion is the predominate cause of acute renal failure. Crystalloid solutions are the first choice to correct fluid and electrolyte deficits in these patients. However, in case of major hypovolemia, particularly in situations of increased capillary permeability, colloid solutions are indicated to achieve sufficient tissue perfusion. Whereas albumin should be avoided for correction of intravascular hypovolemia, synthetic colloids can restore intravascular volume and stabilize hemodynamic conditions. In addition to a faster, more effective and prolonged restoration of intravascular volume, colloid solutions are able to improve microcirculation. Of the synthetic colloids, hydroxyethyl starch (HES) solutions with a low in vivo molecular weight, such as HES 200/0.5, offer the best risk/benefit ratio. These solutions are safe with respect to effects on coagulation, platelets, reticuloendothelial system, and renal function, if used below their upper dosage limits. For patients with acute renal dysfunction, daily monitoring of renal function is necessary if colloids are required to stabilize hemodynamic conditions. In these patients, measurement of the colloidal osmotic pressure and adequate amounts of crystalloid solutions will reduce the risk of hyperoncotic renal failure. Of all colloids, gelatin and HES solutions with low in vivo molecular weight are preferred in these cases. In the very specific situation of kidney transplantation, colloid solutions should be administered in a restricted manner to organ donors and kidney recipients.

Acute Kidney Injury↗

Monitoring of organ dysfunction in sepsis/systemic inflammatory response syndrome: novel strategies.

Sepsis and systemic inflammatory response syndrome-induced severe disruption of microcirculation and consecutive tissue hypoxia is considered a key factor in the development of organ dysfunction and multiple organ failure. The conventionally measured global variables such as lactate or macrohemodynamic parameters using a pulmonary artery catheter do not adequately mirror microcirculatory disturbances. Evaluation of the severity of microcirculatory distress and the effectiveness of resuscitation strategies requires new clinical technologies aimed at the microcirculation. It is anticipated that novel techniques such as optical spectroscopy and intelligent biosensors will play a major role in the development of new monitoring systems. In general, the current monitoring of organ dysfunction is characterized by a trend from invasive to noninvasive and "safe" techniques, which provide bedside or even on-line monitoring and allow a more precise and earlier detection of organ dysfunction. Techniques for the assessment of regional perfusion and microcirculatory bioenergetics to direct therapeutic procedures are expected to refine and optimize clinical treatment of critically ill patients in the future. This article addresses the question of which variables should be monitored, what is feasible, and what is valid for therapeutic consequences. Recent developments in monitoring of macro- and microcirculation and organ-specific dysfunction, e.g., lung, kidney, are described with respect to their advantages and limitations, and future directions are outlined.

Humans↗

The domination of chronic illness research by biomedical interests.

The interest of biomedicine is the physical body viewed in isolation from the contextual understandings which shape the chronic illness experience. This neglect of the illness experience was evident in an inquiry conducted by the first author with 81 women who live with chronic illness. Herein we discuss a secondary analysis of the correspondence data in which we found many common elements across different medical diagnoses.

Chronic Disease↗

Homo- and heterodimerization of somatostatin receptor subtypes. Inactivation of sst(3) receptor function by heterodimerization with sst(2A).

Several recent studies suggest that G protein-coupled receptors can assemble as heterodimers or hetero-oligomers with enhanced functional activity. However, inactivation of a fully functional receptor by heterodimerization has not been documented. Here we show that the somatostatin receptor (sst) subtypes sst(2A) and sst(3) exist as homodimers at the plasma membrane when expressed in human embryonic kidney 293 cells. Moreover, in coimmunoprecipitation studies using differentially epitope-tagged receptors, we provide direct evidence for heterodimerization of sst(2A) and sst(3). The sst(2A)-sst(3) heterodimer exhibited high affinity binding to somatostatin-14 and the sst(2)-selective ligand L-779,976 but not to the sst(3)-selective ligand L-796,778. Like the sst(2A) homodimer, the sst(2A)-sst(3) heterodimer stimulated guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) binding, inhibition of adenylyl cyclase, and activation of extracellular signal-regulated kinases after exposure to the sst(2)-selective ligand L-779,976. However, unlike the sst(3) homodimer, the sst(2A)-sst(3) heterodimer did not promote GTPgammaS binding, adenylyl cyclase inhibition, or extracellular signal-regulated kinase activation in the presence of the sst(3)-selective ligand L-796,778. Interestingly, during prolonged somatostatin-14 exposure, the sst(2A)-sst(3) heterodimer desensitized at a slower rate than the sst(2A) and sst(3) homodimers. Both sst(2A) and sst(3) homodimers underwent agonist-induced endocytosis in the presence of somatostatin-14. In contrast, the sst(2A)-sst(3) heterodimer separated at the plasma membrane, and only sst(2A) but not sst(3) underwent agonist-induced endocytosis after exposure to somatostatin-14. Together, heterodimerization of sst(2A) and sst(3) results in a new receptor with a pharmacological and functional profile resembling that of the sst(2A) receptor, however with a greater resistance to agonist-induced desensitization. Thus, inactivation of sst(3) receptor function by heterodimerization with sst(2A) or possibly other G protein-coupled receptors may explain some of the difficulties in detecting sst(3)-specific binding and signaling in mammalian tissues.

Adenylyl Cyclases↗

Limited participation of 5-HT(1A) and 5-HT(2A/2C) receptors in the clozapine-induced Fos-protein expression in rat forebrain regions.

Through the development of tolerance following long-term clozapine treatment, we investigated whether 5-HT(1A) and 5-HT(2A/2C) receptors participate in the clozapine-induced Fos-protein expression in the rat forebrain. Tolerance exists when the acutely increased Fos responses to a challenge dose of the 5-HT(1A) and 5-HT(2A/2C) agonists 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane-hydrochloride (DOI) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), respectively, given simultaneously to rats, are attenuated after 3-week clozapine (20 mg kg(-1) day(-1) i.p.) pretreatment. As compared to the acute effects of clozapine, the Fos responses to concomitant administration of the 5-HT receptor agonists DOI (2.5 mg kg(-1) i.p. ) and 8-OH-DPAT (2.5 mg kg(-1) i.p.) were more pronounced in the prefrontal cortex, the nucleus accumbens core and the dorsomedial and ventromedial striatum, areas in which clozapine (20 mg kg(-1) i. p.) exhibited marginal effects. In the hypothalamic paraventricular nucleus, both clozapine and DOI/8-OH-DPAT induced a remarkably high number of Fos-positive nuclei. Long-term clozapine pretreatment attenuated the acutely induced Fos expression of the 5-HT receptor agonists in the nucleus accumbens core, the dorsomedial and ventromedial parts of the striatum and the lateral septum, indicating (partial) common sites of action of the agents in these brain regions. No tolerance was found in the nucleus accumbens shell and the hypothalamic paraventricular nucleus and the central amygdala, suggesting that the clozapine-induced Fos responses, though distinct in these regions, are independent of 5-HT receptors. The prefrontal cortex and the dorsolateral striatum indicated only a tendency towards tolerance. In addition, the involvement of the tested 5-HT receptor agonists in the clozapine-enhanced release of plasma corticosterone became apparent. The present results indicate that the clozapine-induced patterns of Fos expression in the rat forebrain can only be in part attributed to an interaction with 5-HT(1A/2A/2C) receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

A novel nemaline myopathy in the Amish caused by a mutation in troponin T1.

The nemaline myopathies are characterized by weakness and eosinophilic, rodlike (nemaline) inclusions in muscle fibers. Amish nemaline myopathy is a form of nemaline myopathy common among the Old Order Amish. In the first months of life, affected infants have tremors with hypotonia and mild contractures of the shoulders and hips. Progressive worsening of the proximal contractures, weakness, and a pectus carinatum deformity develop before the children die of respiratory insufficiency, usually in the second year. The disorder has an incidence of approximately 1 in 500 among the Amish, and it is inherited in an autosomal recessive pattern. Using a genealogy database, automated pedigree software, and linkage analysis of DNA samples from four sibships, we identified an approximately 2-cM interval on chromosome 19q13.4 that was homozygous in all affected individuals. The gene for the sarcomeric thin-filament protein, slow skeletal muscle troponin T (TNNT1), maps to this interval and was sequenced. We identified a stop codon in exon 11, predicted to truncate the protein at amino acid 179, which segregates with the disease. We conclude that Amish nemaline myopathy is a distinct, heritable, myopathic disorder caused by a mutation in TNNT1.

Amino Acid Sequence↗

Prolonged c-Jun expression in the basolateral amygdala following bulbectomy: possible implications for antidepressant activity and time of onset.

Olfactory bulbectomy is a well established animal model of depression. Neurochemical and behavioral alterations observed following olfactory bulbectomy, are due, in part, to the neurodegeneration of specific brain structures. Amygdaloid dysfunction in particular, is known to play a substantial role in the syndrome of the olfactory bulbectomized rat. The present study examined both short- and long-term alterations in immediate early gene expression, tyrosine hydroxylase and serotonin immunoreactivity, and classical silver staining, following olfactory bulbectomy in the basolateral amygdala. The results indicated no consistent change in Fos expression observed over the experimental period. Following bulbectomy, long term (up to 64 days post-lesion) Jun expression, not coincident with silver staining, was observed in the basolateral nucleus. The basolateral nucleus was also intensely immunoreactive for serotonin at this timepoint post-bulbectomy. Thus, following bulbectomy long term alterations in Jun expression occurs in the serotonin rich basolateral amygdala. As a site of action for antidepressant compounds, alterations at the immediate early gene level in this region may have implications both for the model, and antidepressant drug action therein.

Amygdala↗

[From isoflurane to perfluorohexane? Perfluorocarbons--therapeutic strategies in acute lung failure].

The introduction of Perfluorochemicals into medicine and especially into the treatment of severe lung injury is a fascinating scientific task. Many recall the famous experiments from Clark et al. in 1966 when he demonstrated "liquidventilation with perfluorocarbons" in the mammal species for the first time. After this hallmark, perfluorocarbons were subsequently introduced in research of acute lung injury by the techniques of Total- and Partial-Liquid-Ventilation (TLV; PLV). Perfluorocarbons (saturated organofluorids) have unique chemical and physical properties which made them attractive substances for intraalveolar application. The strong C-F bindings in the perfluorocarbon molecules are responsible for their chemical stability, biochemical inertness, high capacity to dissolve respiratory gases, low surface tension and high vapor pressures. Furthermore, the high density of the PFC lead to radio-opacity and their distribution to dependent lung areas. The efficacy of PFC liquid, applied by TLV/PLV has been demonstrated in numerous animal studies using different models of acute lung injury. Currently, several mechanisms of action of perfluorocarbon fluids in acute lung injury are discussed: recruitment of atelectatic alveoli, prevention of endexpiratory collapse of alveoli ("liquid PEEP"), redistribution of perfusion, oxygen transport, surfactant like effects and decrease of inflammation. Since total liquid ventilation has been used only in experimental models of lung injury, partial liquid ventilation has been introduced successfully into clinical trials (phase I-II). However, the results of the first randomised, controlled study of PLV in 90 adult patients suffering from severe respiratory failure (ALI/ARDS) showed no differences between PLV and conventional treatment. Furthermore, the instillation of relatively large amounts of liquid into the lungs poses several technical challenges and may be associated with complications such as liquithoraces, pneumothoraces and hypoxia. Since mammal lungs are evolutionary specialised to gas exchange using atmospheric oxygen, the application of liquids, even if they transport respiratory gases very well is not physiologic. To overcome these unwanted side effects, we developed a technique of perfluorocarbon vaporisation in analogy to the application of inhalation anaesthetic agents. After resolving some technical issues, this application technique was used successfully in an animal model of acute lung injury. Vaporisation of perfluorohexane in a concentration of 18 Vol.% of inspired gas improved significantly oxygenation and lung compliance. Though these results are promising, mechanisms of action, dose-efficacy relation, surfactant-perfluorocarbon interaction or anti-inflammatory effects of vaporised perfluorohexane are still unclear. These questions need to be clarified before this technique can be applied clinically. However, the inhalation of vapor, a technique already familiar to anaesthesiologists should avoid risks of large amounts of fluids in the bronchoalveolar space. Furthermore, this technique can be administered by established anaesthetic equipment with the advantage of exact dosing, continuous monitoring, and demand application in a way near to clinical routine.

Anesthetics, Inhalation↗

[Combined anesthesia with epidural catheter. A retrospective analysis of the perioperative course in patients ungoing radical prostatectomy] .

Patients requiring radical prostatectomy (rPE), including retroperitoneal lymphadenectomy are often aged and have coexisting cardiopulmonary diseases, increasing the risk of perioperative complications. The aim of the present study was to evaluate our perioperative anaesthesiologic regimen over the last five years, in terms of safety and patients comfort. Records of 433 patients who underwent rPE between 1994 and 1999 in our hospital were retrospectively reviewed. Patients were divided in those who received: 1. general anaesthesia (GA) alone, 2. a combination of lumbar epidural anaesthesia (LEA) + GA or, 3. thoracic epidural anaesthesia (TEA) + GA. General anaesthesia was performed as balanced anaesthesia, and epidural administered local anaesthetics were bupivacaine 0.25% or ropivacaine 0.2%, 8-12 ml/h. In terms of intra- and postoperative numbers of tachycardiac and hypertensive episodes, a reduced stress response was observed under epidural anaesthesia (EA). Moreover, the weaning duration was shorter under EA and onset of gastrointestinal motility was found earlier ([h] GA: 50.6 +/- 11.1/LEA: 39.3 +/- 13.6/TEA: 33.8 +/- 13.0). Furthermore, a trend to rarer phases of postoperative vomiting and a significant decrease of in hospital stay of about one day ([d] GA: 12.4 +/- 5.8/LEA: 11.1 +/- 3.1/TEA: 11.5 +/- 3.8) was observed. The duration of personnel binding in the OR did not differ significantly between GA and TEA ([min] GA: 222.9 +/- 43.5/LEA: 238.2 +/- 41.8/TEA: 227.0 +/- 46.2), but ICU stay was shortened under TEA. Besides this, TEA reduced the number of pathologic postoperative thorax-x-rays. Senso-motor blockades, decreases of SaO2 and cardiac complications were experienced more frequent under LEA as compared with TEA. Combination of GA and EA, especially TEA, appears to improve perioperative care of patients undergoing rPE, in terms of patients safety and comfort.

Anesthesia, Epidural↗