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Biomedical subjects

M Koch

Publications and source records attributed to M Koch.

At least 127 records · Page 7Linked to original sources
PubMed2000

Pharmacoeconomic impact of rational use guidelines on the provision of analgesia, sedation, and neuromuscular blockade in critical care.

OBJECTIVE: To determine the cost-effectiveness and safety of a set of rational use guidelines for analgesia, sedation, and neuromuscular blockade in critically ill ventilated patients when compared with similar factors in standard prescribing. DESIGN: Prospective cost-benefit analysis. SETTING: Medical and surgical intensive care units (ICU) of a 350-bed tertiary care university hospital. PATIENTS: Patients admitted to our ICUs who required mechanical ventilation and continuous analgesics, sedatives, and/or neuromuscular junction blockers (NMJBs). There were 72 patients in the baseline and 84 patients in the follow-up groups. INTERVENTIONS: Prospective tracking of eligible baseline patients was followed by the development and introduction of guidelines and an academic detailing process to promote the use of guidelines. Several months after the introduction of guidelines, a second group of eligible follow-up patients was tracked. The use and effectiveness of analgesics, sedatives, and NMJBs, as well as cost and outcomes, were followed in both groups. Data were subsequently reviewed and analyzed. MEASUREMENTS AND MAIN RESULTS: We recorded data by means of Paradox and Excel databases and included demographics, costs, outcomes (including adverse drug reactions, functional status, ventilator time in hours, lengths of stay), and mortality rates. Data were subsequently analyzed via the Winks statistical data analysis program. Both groups were similar with regard to demographics. There was a statistically significant increase in severity of illness in the follow-up group without a statistically significant increase in mortality. Direct drug costs, ventilator time, and lengths of stay were reduced in the follow-up group. In addition, the use of NMJBs was reduced from 30% in the baseline group to 5% in the follow-up group. CONCLUSIONS: Rational use guidelines resulted in safe, cost-effective improvements in the provision of continuous analgesia, sedation, and neuromuscular blockade to critically ill patients requiring ventilator management when compared with similar factors in baseline prescribing strategies.

APACHE↗
PubMed2000

Myocardial bradykinin B2-receptor expression at different time points after induction of myocardial infarction.

OBJECTIVE: To characterize the regulation of the myocardial bradykinin B2 receptor after induction of myocardial infarction (MI), we studied its expression at different time points in the left ventricle (LV), right ventricle (RV) and interventricular septum (S) of the heart. DESIGN: Male Sprague-Dawley rats were submitted to permanent occlusion of the left descending coronary artery. Six hours, 24 h or 6 days after MI induction or a sham operation, a Millar-tip catheter was placed in the LV. Left ventricular pressure (LVP) and contractility [(dP/dt)max] were measured. The LV, RV and S of all animals were isolated, and total RNA was extracted. B2-receptor expression was analysed by an RNase-protection assay. In addition, Western blot analysis was used to determine protein levels of the B2 receptor in the infarcted area of the LV. RESULTS: We observed a decrease in LVP and contractility at all time points after MI in comparison with sham-operated animals. Basal B2-receptor expression was detected in the LV and RV, but not in the S of sham-operated rats. In the LV of infarcted hearts, we found a time-dependent up-regulation of the B2-receptor expression, which was increased twofold and fivefold, respectively, 6 h and 24 h after induction of MI compared with controls. This increase was maintained for at least 6 days. Similarly, we also found an up-regulation of the B2-receptor expression in the RV and S. Both reached a peak 24 h after induction of MI. The protein level of the receptor gradually increased up to day 6. CONCLUSION: We conclude that myocardial ischaemia triggers B2-receptor up-regulation in both the infarcted and non-infarcted areas of the heart.

Animals↗
PubMed2000

Rhabdomyolysis and acute renal failure after changing statin-fibrate combinations.

Statin-fibrate combinations are commonly used to treat hyperlipidemia. These drugs have been previously reported to cause rhabdomyolysis with acute renal failure. Whether different statin-fibrate combinations have different risks for rhabdomyolysis is not known. We report a patient who developed rhabdomyolysis with acute renal failure promptly after switching from the combination of pravastatin and fenofibrate to simvastatin and gemfibrozil.

Acute Kidney Injury↗
PubMed2000

Association of a polymorphism in the TNFR2 gene with low bone mineral density.

Previous genetic linkage data suggested that a gene on chromosome 1p36.2-36.3 might be linked to low bone mineral density (BMD). Here, we examine the gene for tumor necrosis factor receptor 2 (TNFR2), a candidate gene within that interval, for association with low BMD in a group of 159 unrelated individuals. We assess two polymorphic sites within the gene, a microsatellite repeat within intron 4, and a three-nucleotide variation in the 3' untranslated region (UTR) of the gene. The latter has five alleles of which the rarest allele is associated with low spinal BMD Z score (p = 0.008). Lowest mean spinal BMD Z scores were observed for individuals having genotypes that were heterozygous for the rarest allele. No homozygotes for the rarest allele were observed. Preliminary analysis suggests that there is a difference in the genotype frequency distribution between the group with low BMD and a control group.

3' Untranslated Regions↗
PubMed2000

[Diagnosis and significance of minimal residual disease in patients with colorectal carcinoma].

Progression of malignant tumours to metastatic disease after surgery in curative intent is due to usually few and with conventional diagnostic techniques undetectable residual malignant cells. These cells must have been spread either before or during surgery. The more sensitive and specific detection of these malignant cells in various clinically relevant compartments of the patients organism became possible through new immunocytochemical and molecular tools. Various clinical studies underline the strong prognostic impact of the detection of disseminated cancer cells. However, many technical aspects did not yet allow sufficient standardization of these procedures and led to significantly varying results among different scientific groups. It is one of our primary aims to test, whether the detection of disseminated cancer cells might guide the indication for adjuvant therapies and might predict the efficacy of therapies in patients with solid cancers.

Blood↗
PubMed1999

Lesions of the rat piriform cortex prevent long-lasting sensorimotor gating deficits induced by stimulation of the ventral hippocampus.

Prepulse inhibition (PPI) is a cross-species operational measure of sensorimotor gating. Reduced PPI is found in schizophrenics and can be induced experimentally in rats. Stimulation of the rat ventral hippocampus (VH) with N-methyl-D-aspartate (NMDA) results in long-lasting PPI deficits (carry-over effect). Since we have previously shown that this carry-over effect was accompanied by increased expression of c-Fos in the piriform cortex (PIR), we here tested the effects of lesions of the PIR on PPI after stimulation of the VH. PIR lesioned rats still showed disruption of PPI after injection of NMDA into the VH. However, the carry-over effect observed in controls was prevented by PIR lesions. These data suggest that the PIR is important for long-lasting alterations in brain functioning leading to impaired sensorimotor gating.

Analysis of Variance↗
PubMed1999

Myocardial expression of rat bradykinin receptors and two tissue kallikrein genes in experimental diabetes.

To characterize the role of the kallikrein-kinin system in diabetic cardiopathy, we studied the effect of streptozotocin (STZ) on the regulation of the myocardial bradykinin (BK) receptors, the B1 and B2 type, and two tissue kallikrein genes, rat kallikrein 1 (rKLK1) and rKLK7, in severely hyperglycemic rats. Experiments were performed in STZ-induced diabetic male Wistar rats (n = 7) and compared to controls (n = 7). After extraction of myocardial total RNA, specific oligonucleotides were used to generate reverse transcription PCR (RT-PCR) products from myocardial rKLK1 and rKLK7 mRNA. Southern blot analyses of these RT-PCR products were hybridized with appropriate gene-specific oligonucleotide probes. Myocardial B1 and B2 receptor expression were analyzed by RNase protection assays using specific probes from the coding region of the receptor genes. Twelve weeks after diabetes induction, the rats were normotensive and hyperglycemic and polyuric. We observed an impairment of the main myocardial kinin-forming enzymes, indicated by a reduction of the expression of both, rKLK1 and rKLK7. At this time the myocardial expression of the B1 receptor was not detectable in either group. Thus, the B1 receptor does not play a regulatory role in either the healthy or in STZ-diabetic heart. In contrast, the B2-receptor expression was detectable but did not differ significantly in either group. The reduced synthesis of myocardial tissue KLK implies a reduced capacity to generate BK in diabetic rats. This reduction is not compensated by elevated BK receptor levels. We suggest that alterations of the KKS may contribute to myocardial dysfunction in diabetes mellitus.

Animals↗
PubMed1999

Upregulation of the cardiac bradykinin B2 receptors after myocardial infarction.

An increase in myocardial bradykinin (BK) might be a mechanism to protect the heart during acute myocardial infarction (MI). To characterize the regulation of the myocardial B2 receptor during MI, we studied the expression of this BK receptor in the right ventricle (RV), left ventricle (LV) and myocardial septum (S) 24 h after left coronary ligation. Experiments were performed in male Wistar Kyoto rats (n = 10) and compared with sham operated animals (n = 6). After total RNA extraction, the myocardial B2-receptor expression was analyzed by a RNase protection assay (n = 6), using a specific probe from the coding region of the receptor gene. After 24 h, rats with MI were normotensive and showed an impaired left ventricular function. The B2-receptor expression of the LV of these rats was significantly elevated (2.3-fold) compared to sham operated rats. Furthermore, we found a dramatic upregulation of the B2 receptor in the RV (7.8-fold) and a dramatic expression of B2 receptor mRNA in S of infarcted hearts, whereas in the S of sham operated rats no B2 receptor expression could be detected. Our data show clearly that the described increase in BK during myocardial ischemia is accompanied by an elevated B2-receptor expression in the infarcted and non-infarcted parts of cardiac ventricles.

Animals↗
PubMed1999

Characterization and expression of the laminin gamma3 chain: a novel, non-basement membrane-associated, laminin chain.

Laminins are heterotrimeric molecules composed of an alpha, a beta, and a gamma chain; they have broad functional roles in development and in stabilizing epithelial structures. Here, we identified a novel laminin, composed of known alpha and beta chains but containing a novel gamma chain, gamma3. We have cloned gene encoding this chain, LAMC3, which maps to chromosome 9 at q31-34. Protein and cDNA analyses demonstrate that gamma3 contains all the expected domains of a gamma chain, including two consensus glycosylation sites and a putative nidogen-binding site. This suggests that gamma3-containing laminins are likely to exist in a stable matrix. Studies of the tissue distribution of gamma3 chain show that it is broadly expressed in: skin, heart, lung, and the reproductive tracts. In skin, gamma3 protein is seen within the basement membrane of the dermal-epidermal junction at points of nerve penetration. The gamma3 chain is also a prominent element of the apical surface of ciliated epithelial cells of: lung, oviduct, epididymis, ductus deferens, and seminiferous tubules. The distribution of gamma3-containing laminins on the apical surfaces of a variety of epithelial tissues is novel and suggests that they are not found within ultrastructurally defined basement membranes. It seems likely that these apical laminins are important in the morphogenesis and structural stability of the ciliated processes of these cells.

Amino Acid Sequence↗
PubMed1999

Cholinergic modulation of the acoustic startle response in the caudal pontine reticular nucleus of the rat.

The startle response is a useful behavioural model to assess drug effects on sensorimotor information processing in the mammalian central nervous system. Prepulse inhibition of the acoustic startle response in rats is an operational measure for sensorimotor gating mechanisms which may be necessary for attention and response selection. The caudal pontine reticular nucleus is a key element of the pathway that mediates the acoustic startle response and receives an inhibitory cholinergic projection that might be important for prepulse inhibition. The present study tested whether prepulse inhibition of acoustic startle is modulated by microinfusions of the muscarinic/nicotinic acetylcholine receptor agonist carbachol and of the muscarinic acetylcholine receptor antagonist scopolamine. Carbachol (0-40 nmol/0.5 microl) dose dependently attenuated startle and enhanced prepulse inhibition. Scopolamine (0-40 nmol/0.5 microl) dose-dependently enhanced startle and reduced prepulse inhibition at a dose of 10 nmol. Scopolamine (40 nmol) also increased the spontaneous motor activity of the rats. These findings lend support to the hypothesis that muscarinic acetylcholine receptors in the caudal pontine reticular nucleus inhibit the acoustic startle response and are involved in the mediation of prepulse inhibition of startle.

Acoustic Stimulation↗
PubMed1999

Rapid and reversible regulation of collagen XII expression by changes in tensile stress.

We studied the expression of the fibril-associated collagen XII by fibroblasts cultured on attached (stretched) or floating (relaxed) collagen I gels. Accumulation of collagen XII in the medium as determined by semiquantitative immunoblotting was 8-16 times higher under stretched compared to relaxed conditions. Northern blot experiments showed that tensile stress controls collagen XII expression at the mRNA level. Tenascin-C mRNA levels were also influenced, whereas relative amounts of fibronectin and matrix metalloproteinase-2 mRNA were barely affected. The response to a change in tensile stress is rapid, since de novo biosynthesis of collagen XII was fully down-regulated 12 h after relaxation of a stretched culture. To demonstrate that the effect is also reversible, we mounted collagen gels with attached cells to movable polyethylene plugs. The cultures were relaxed or stretched at intervals of 24 and 48 h, and media samples were analyzed every 24 h. By ELISA, the amount of collagen XII secreted into the medium was found to increase or decrease in accordance with the tensile stress applied. This is evidence that the mechanical stimulus per se, rather than an indirect secondary effect, was responsible for the observed changes in collagen XII production.

Animals↗
PubMed1999

Lesions of the nucleus basalis magnocellularis do not impair prepulse inhibition and latent inhibition of fear-potentiated startle in the rat.

The present study tested if lesions of the nucleus basalis magnocellularis (NBM) affect prepulse inhibition (PPI) of the acoustic startle response and latent inhibition (LI) of fear-potentiated startle. The NBM is known to play an important role in learning and memory. Recently, the interest of research focused on its role in attentional and response selection processes. We here tested the effect of excitotoxic NBM-lesions on PPI, a phenomenon of sensorimotor gating that occurs at early stages of information processing. We also assessed the lesion effects on LI, a phenomenon of reduced conditioning after stimulus preexposure that can be used to measure selective attention. Bilateral infusions into the NBM of 80 nmol of quinolinic acid markedly reduced the number of choline acetyltransferase immunopositive neurons in the NBM and lead to a pronounced reduction of acetylcholine esterase in the cortex and the amygdala. However, no effects on PPI, fear-conditioning, or LI of fear-potentiated startle were found. Therefore, we conclude that there is no NBM-driven attentional or response selection process involved in PPI. Furthermore, the simple association learning in the classical conditioning paradigm used for fear-potentiated startle or LI is unaffected by NBM-lesions.

Acoustic Stimulation↗
PubMed1999

[meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] sulfatoplatinum(II)--pharmacokinetic studies.

The maximally attainable level of the non-plasma protein bound fraction of a single 10.0 mumol/kg i.p. dose of [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] sulfatoplatinum(II), a drug active on the murine, hormone-sensitive MXT-M-3.2 breast cancer, lies markedly below the concentration causing a significant cytotoxic effect on a cell line derived from this tumor. This result confirms our opinion that the strong in vivo activity of this drug on hormone-sensitive breast cancers is mediated by its estrogenic potency by analogy with high dosed steroidal and non-steroidal estrogens. A specific cytotoxic effect utilizing the estrogen receptor as carrier, as formerly postulated, is unlikely.

Animals↗
PubMed1999

On the Reversible Conjugation of

After administering [17-D(2)]GA(20) to Phaseolus coccineus L. cv. Preisgewinner seedlings, [17-D(2)]GA(20)-O-glucoside was identified by liquid chromatography (LC)/ESI-tandem mass spectrometry (MS). Likewise, by LC/ESI-tandem MS the metabolic formation of [17-D(2)]GA(20) glucosyl ester was established. The application of both [17-D(2)]-labeled GA(20) 13-O-glucoside and GA(20) glucosyl ester to Phaseolus coccineus L. seedlings resulted in free [17-D(2)]GA(20) by gas chromatography/MS. The results demonstrate that conjugation of GA(20) and the reconversion of the glucosyl conjugates are concomitant processes in plants.

Journal Article↗
PubMed1999

[The subacromial shoulder dislocation].

We report on a case of subacromial shoulder dislocation, which resulted from a combination of a cranial glenoid fracture and an acromial fracture. The patient sustained this rare injury while playing handball. The whole implication of the injury was revealed only after extensive workup with CT scan of the shoulder. After reduction of the shoulder dislocation, the glenoid fracture was stabilized by osteosynthesis. The postoperative results showed anatomical reconstruction of the glenoid joint surface. After completion of therapy, the patient has achieved good functional results with a full range of motion (abduction 180 degrees ) and has been able to work full-time again.

Acromioclavicular Joint↗