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Biomedical subjects

K Koch

Publications and source records attributed to K Koch.

At least 55 records · Page 3Linked to original sources
PubMed1996

Continued benefit of coronary stenting versus balloon angioplasty: one-year clinical follow-up of Benestent trial. Benestent Study Group.

OBJECTIVES: This study sought to determine the 1-year clinical follow-up of patients included in the Benestent trial. BACKGROUND: The Benestent trial is a randomized study comparing elective Palmaz-Schatz stent implantation with balloon angioplasty in patients with stable angina and a de novo coronary artery lesion. Seven-month follow-up data have shown a decreased rate of restenosis and fewer clinical events in the stent group. It is not established whether this favorable clinical outcome is maintained for longer periods or whether coronary stenting defers restenosis and its subsequent clinical manifestations. METHODS: To clarify this uncertainty, we updated clinical information on all but 1 of 516 patients enrolled in the Benestent trial (257 in balloon group, 259 in stent group) at least 12 months after the intervention. Major clinical events (primary clinical end point) were tabulated according to the intention to treat principle and included death, the occurrence of a cerebrovascular accident, myocardial infarction, the need for bypass surgery or a further percutaneous intervention in the previously treated lesion. RESULTS: After 1 year, no significant differences in mortality (1.2% vs. 0.8%), stroke (0.0% vs. 0.8%), myocardial infarction (5.0% vs. 4.2%) or coronary bypass graft surgery (6.9% vs. 5.1%) were found between the stent and balloon angioplasty groups, respectively. However, the requirement for a repeat angioplasty procedure was significantly lower in the stent group (10%) than the balloon angioplasty group (21%, relative risk [RR] 0.49, 95% confidence interval [CI] 0.31 to 0.75, p = 0.001), and overall primary end points were less frequently reached by stent group patients (23.2%) than those in the balloon group (31.5%, RR 0.74, 95% CI 0.55 to 0.98, p = 0.04). No differences were found between groups with respect to functional class angina and prescribed medication at the time of follow-up. CONCLUSIONS: These clinical follow-up data show that the benefit of elective native coronary artery stenting in patients with stable angina is maintained to at least 1 year after the procedure and results in a significantly reduced requirement for repeat intervention.

Angina Pectoris↗
PubMed1996

Phosphorylation of serine-15 of maize leaf sucrose synthase. Occurrence in vivo and possible regulatory significance.

Experiments were conducted to determine whether sucrose synthase (SuSy) was phosphorylated in the elongation zone of maize (Zea mays L.) leaves. The approximately 90-kD subunit of SuSy was 32P-labeled on seryl residue(s) when excised shoots were fed [32P]orthophosphate. Both isoforms of SuSy (the SS1 and SS2 proteins) were phosphorylated in vivo, and tryptic peptide-mapping analysis suggested a single, similar phosphorylation site in both proteins. A combination of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and automated Edman sequencing analysis unequivocally identified the phosphorylation site in the maize SS2 protein as serine-15. This site was phosphorylated in vitro by endogenous protein kinase(s) in a strictly Ca(2+)-dependent manner. A synthetic peptide, based on the phosphorylation site sequence, was used to identify and partially purify an endogenous Ca(2+)-dependent protein kinase(s) from the maize leaf elongation zone and expanding spinach leaves. Phosphorylation of SuSy in vitro selectively activates the cleavage reaction by increasing the apparent affinity of the enzyme for sucrose and UDP, suggesting that phosphorylation may be of regulatory significance. Conservation of the phosphorylation site, and the sequences surrounding it, among plant species suggests that phosphorylation of SuSy may be widespread, if not universal, in plants.

Amino Acid Sequence↗
PubMed1996

Characterization of the pharmacological profile of the potent LTB4 antagonist CP-105,696 on murine LTB4 receptors in vitro.

1. Binding of [3H]-leukotriene B4 ([3H]-LTB4) to murine spleen membranes (MSM) was determined. 2. Scatchard analyses of [3H]-LTB4 binding indicated the presence of high (KD1 = 1.7 nM) and low (KD2 = 7.5 nM) affinity receptors on MSM with Bmax values of 151 fmol mg-1 protein (Bmax1) and 354 fmol mg-1 protein (Bmax2), respectively. 3. CP-105,696, a potent LTB4 antagonist, inhibited [3H]-LTB4 (0.67 nM) binding to the high affinity receptor on MSM, IC50 = 30.2 nM, Ki = 17.7 nM with a Hill coefficient of 0.93. 4. Scatchard analyses of [3H]-LTB4 binding to MSM in the presence of CP-105,696 indicated that the high-affinity receptor was inhibited in a non-competitive manner and the low-affinity receptor in a competitive manner. 5. Isolated peripheral blood murine neutrophils (MN) responded chemotactically to LTB4, EC50 = 2.5 nM. CP-105,696 blocked this response, IC50 = 2.3 nM. When examined over a full concentration-response range of LTB4, CP-105,696 inhibited chemotaxis in a non-competitive manner. 6. Murine neutrophils in anticoagulated whole blood upregulated the integrin, complement receptor type 3 (CD11b/CD18, Mac-1) in response to LTB4, EC50 = 20 nM and this was inhibited by CP-105,696 in a competitive manner. 7. These results provide evidence that MSM have specific binding sites for LTB4, and as exemplified by CP-105,696, that these receptors may be useful for determining the potency and nature of antagonism of novel LTB4 receptor antagonists.

Animals↗
PubMed1995

Leukotriene B4 plays a critical role in the progression of collagen-induced arthritis.

Leukotriene B4 (LTB4) is a product of the 5-lipoxygenase pathway of arachidonic acid metabolism. LTB4 is a potent chemotactic factor for neutrophils and has been postulated to play an important role in a variety of pathological conditions including rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease. The role of LTB4 in such diseases has not yet been defined but in this paper we provide direct evidence that LTB4 plays a critical role in a murine model of RA. CP-105,696, (+)-1-(3S,4R)-[3-(4-phenylbenzyl)- 4-hydroxychroman-7-yl]cyclopentane carboxylic acid, is an LTB4 receptor antagonist that inhibits LTB4 binding to human neutrophil membranes with an IC50 of 3.7 nM and inhibits LTB4-induced chemotaxis of these cells with an IC50 of 5.2 nM. CP-105,696 inhibits LTB4-induced neutrophil influx in mouse skin when administered orally with an ED50 of 4.2 mg/kg. CP-105,696 had a dramatic effect on both the clinical symptoms and histological changes of murine collagen-induced arthritis when administered at doses of 0.3-10 mg/kg. Inhibition was not associated with suppression of the humoral immune response to collagen and was equally effective if drug treatment was commenced just prior to the onset of arthritis or throughout the experiment. These results suggest that LTB4 receptor antagonists may be effective therapeutic agents for the treatment of RA.

Animals↗
PubMed1995

The negative inotropic and chronotropic effects of intravenous R 56865 during percutaneous transluminal coronary angioplasty.

The present study was designed to evaluate the potential anti-ischaemic activity of R 56865 in patients with coronary artery disease, scheduled to undergo percutaneous transluminal coronary angioplasty (PTCA). At baseline a complete haemodynamic profile, including cardiac output and coronary sinus blood flow (CSBF) was obtained. In addition, left ventricular pressure and contractility parameters were measured. These parameters were also measured before and after additional balloon inflations, preceded by placebo and R 56865 i.v. R 56865 was infused intravenously at three different dosages, namely: 20 mg (n = 8), 30 mg (n = 2), 40 mg (n = 2). No significant differences were observed between placebo and R 56865 (20 mg) concerning time to onset and duration of ST-segment changes and symptomatic angina pectoris, respectively. The other parameters did not show differences compared with the baseline values when R 56865 (20 and 30 mg) was infused. However, the two patients receiving a dose of 40 mg R 56865 developed a dramatic decrease in systolic and diastolic blood pressure, left ventricular (LV) systolic pressure, peak positive dP/dt and the CSBF (ranging from 30-50%), while the LV end-diastolic pressure increased by 100%. The two patients who received this dose became pale and cyanotic and did not respond to verbal commands. In summary, no anti-ischaemic effects of R 56865 were observed under these conditions, whereas at the highest dose (40 mg) R 56865 induced hypotension and a reduction in cardiac contractile force.

Angioplasty, Balloon, Coronary↗
PubMed1995

[Physiologic parameters and locomotor activity in Fleckvieh and Schwarzbund cattle during an alpine summer].

The investigation on an alpine pasture was performed on 15 heifers of the breeds Fleckvieh and Friesians from different farms. Some physiological parameters and locomotor activities in dependence of breed, farm of origin and weather conditions were studied. Animals of one farm were pastured in spring, the animals of the other farm were brought directly from the barn to the mountain area. Physiological parameters were influenced by farm, but not by breed. The activities of GOT and CK increased in unprepared heifers only (due to the release from skeletal muscles) as did levels of free fatty acids and beta-hydroxybutyrate obviously due to adaptation-difficulties linked with energy-deficiency. Pre-pastured animals showed higher blood-urea concentrations, due to their ability to locate always fresh grass with high protein content. The breed influence on the daily number of steps and on the distance covered was statistically not significant. Animals already pastured in spring showed more movement than unprepared ones. Among weather conditions thunderstorm showed a striking increase in activity which resulted from the search for shelter. On rainy days without wind the animals showed least movement. Cloudy, dry weather as well as sunshine was associated with average activity. These reactions to meteorological conditions were manifested more clearly in prepared heifers. The other animals obviously had to learn first how to minimize untoward effects by suitable behaviour.

Animals↗
PubMed1994

Comparison of apical leakage between Ketac Endo sealer and Grossman sealer.

Forty-eight extracted human teeth were prepared for study to compare Ketac Endo cement with Grossman's cement in preventing leakage of a dye. Four groups were formed: (1) Grossman's sealer with a single gutta percha cone; (2) Grossman's sealer with lateral condensation of gutta percha; (3) Ketac Endo sealer with a single cone of gutta percha; and (4) Ketac Endo sealer with lateral condensation of gutta percha. The teeth were immersed in the dye for 10 days, after which they were rinsed in running tap water and cleared for observation. In the groups of teeth evaluated by three individual evaluators, the results consistently showed less leakage with glass ionomer sealers (groups 3 and 4) than with the Grossman's sealers (groups 1 and 2). The best results were noted when Ketac Endo sealers were used with lateral condensation.

Dental Leakage↗
PubMed1994

Functional reorganization in the rat dorsal horn during an experimental myositis.

In anaesthetized rats, the influence of an acute inflammation (2-8 h duration) of the gastrocnemius-soleus (GS) muscle on the excitability of dorsal horn neurones was studied using a mapping procedure. One of the main effects of the myositis was that the neurone population responding to GS A-fibre input increased in size. The increase was most marked in the lateral segments L6-L3 which received little input from the GS muscle in control animals. Excitability testing showed a myositis-induced lowering in threshold, combined with an increase in latency, jitter and input convergence. This suggests that new oligo- or polysynaptic connections become functional under the influence of a myositis. Neuronal effects induced by C fibres in the GS nerves were not significantly altered by a myositis, but C fibre-induced activations from the peroneal and sural nerves increased in the lateral dorsal horn. The results show that an acute myositis leads to marked changes in the functional connectivity of the dorsal horn within a few hours. The main increase in excitability took place in the lateral dorsal horn, where many neurones acquired a new input from the GS muscle. This mechanism may be involved in the spread or referral of muscle pain.

Animals↗
PubMed1994

Gene therapy for the treatment of malignant brain tumors with in vivo tumor transduction with the herpes simplex thymidine kinase gene/ganciclovir system.

Murine retroviral vectors can infect a wide variety of proliferating mammalian cell types (e.g. lymphocytes). Non-proliferating tissues (e.g. neurons) are not transduced by murine retroviral vectors. These findings suggest that this type of vector may be useful for the selective introduction of genes into growing tumors in the brain, since the tumor is essentially the only tissue that will integrate and express the vector genes.

Adult↗
PubMed1993

[Pancreas penetration by ofloxacin--a pilot study].

The use of antibiotics in patients with necrotizing pancreatitis is indicated since bacterial complications are the most common cause of death in this condition. Olfloxacin was studied in six patients regarding its permeation into pancreatic juice and bile and into pancreatic tissue in cases of chronic pancreatitis and pancreatic carcinoma. The peak concentrations in pancreatic juice (3.7 mg/l) and bile (12.9 mg/l) were found 20 minutes after i.v. administration of 3 mg/kg ofloxacin, these are 79 and 275% of the corresponding serum level, respectively. Pancreatic tissue concentrations varied between 54 and 333% of serum values in relation to the removal time of specimens and to the stage of inflammation. After three days and five days of ofloxacin treatment with doses of 2 x 200 mg daily even in pancreatic necroses concentrations were detected between 0.8 and 3.7 mg/kg wet weight. This suggests that in all pancreatic compartments analyzed, sufficient antibacterial ofloxacin levels above the MIC of relevant germs were found. Therefore, from a pharmacokinetic point of view, ofloxacin could be a potentially effective drug in prophylaxis and therapy of bacterial infections of the pancreas.

Adenocarcinoma, Mucinous↗