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Biomedical subjects

M Köhler

Publications and source records attributed to M Köhler.

At least 127 records · Page 7Linked to original sources
PubMed1995

Conscious sedation for gastroscopy: patient tolerance and cardiorespiratory parameters.

BACKGROUND/AIMS: Most patients receive conscious sedation for gastroscopy. However, the benefit of the most often used combination of low-dose intravenous midazolam and topical lidocaine on patient tolerance remains poorly defined and has not been shown to outweigh cardiorespiratory risks. To respond to these issues, a randomized, double-blind, placebo-controlled prospective study was performed. METHODS: Two hundred outpatients undergoing diagnostic gastroscopy were assigned to receive either (1) midazolam (35 micrograms/kg) and lidocaine spray (100 mg), (2) midazolam and placebo lidocaine, (3) placebo midazolam and lidocaine, or (4) placebo midazolam and placebo lidocaine. RESULTS: Tolerance (visual analogue scale, 0-100 points; 0, excellent; 100, unbearable) improved as compared with placebo midazolam and placebo lidocaine by 23 points (95% confidence interval, 15-32) in group 1, 15 points (95% confidence interval, 7-24) in group 2, and 10 points (95% confidence interval, 2-18) in group 3. Increasing age (P < 0.001), low anxiety (P < 0.001), and male sex (P < 0.03), but not amnesia, were associated with better patient tolerance. Oxygen desaturation (< 1 minute) occurred in 8.2% and was not more frequent after midazolam treatment. Hypotension was rare (2.1%), and no adverse outcome occurred. CONCLUSIONS: Both low-dose midazolam (35 micrograms/kg) and lidocaine spray have an additive beneficial effect on patients tolerance and rarely induce significant alterations in cardiorespiratory monitoring parameters, thus supporting the widespread use of conscious sedation.

Adult↗
PubMed1995

Flow cytometric analyses of the subclasses of red cell IgG antibodies.

We report on flow cytometric IgG subclass determinations of red cell antibodies using polyclonal FITC-labeled antibodies. The limit of detection of this method was 1 ng anti-D per 1 x 10(7) red cells. The inter- and intra-assay coefficients of variance were 8.2 and 2.3%, respectively. In 8 newborns with a positive direct antiglobulin test (DAT) in the gel centrifugation test (GCT), due to ABO antibodies, IgG1 was detected in all and IgG2 additionally in 4 of these cases. In 5 severe cases of hemolytic disease of the newborn (HDN) due to anti-D, large amounts of IgG1 were found, and in 3 of these 5, IgG3 in combination with IgG1. In 8 mild or moderate HDN cases (4 anti-D, 2 anti-E, 1 anti-Fya, 1 anti-Jka), phototherapy sufficed, and IgG1 was the only antibody. In 7 adult patients with malignant lymphoma and a positive DAT (GCT), only small amounts of IgG1 red cell autoantibodies could be demonstrated by flow cytometry. In 5 further patients with malignant lymphoma, a positive DAT, and severe hemolytic anemia, large amounts of IgG1 autoantibodies were found and IgG3 was also present in 3 of these cases. Flow-cytometric determination of IgG subclasses may be a useful tool in immunohematology, since subclass determinations were possible in all of these cases. This method is suited for clinical routine and offers the possibility of sufficient standardization.

Adult↗
PubMed1995

Prestorage leukocyte depletion with in-line filtration of whole blood in comparison with blood component leukocyte depletion.

In-line filtration of blood components appears to be an effective method to reduce white-cell-induced adverse reactions. We have investigated whether whole blood filtration (WBF), prior to component preparation, is comparable with filtration of already prepared blood components (CF), i.e. the red cell concentrate (RCC) and fresh plasma. Conventionally prepared nonfiltered blood components served as a control. No significant differences for most parameters investigated were found between leukodepleted RCCs and plasma units prepared by CF or WBF. All filtered RCCs and plasma units (CF and WBF) had white blood cell contaminations < 1 x 10(5) per unit. Platelets were reduced in all filtered components: 95% in plasma and 99% in RCCs. Fresh-frozen plasma (FFP) prepared by CF and WBF had normal amounts of factors V, VIII, von Willebrand factor and thrombin-antithrombin-III complexes, whereas platelet factor 4 (PF-4) was slightly increased in FFP prepared by WBF. RCCs and plasma units prepared from filtered whole blood (n = 20) had a significantly greater volume (RCC: 288 +/- 19 ml; plasma: 274 +/- 20 ml) than conventionally prepared (n = 20) and filtered products (RCC: 257 +/- 19 ml, plasma: 259 +/- 19 ml). For early filtration of blood components, WBF prior to component preparation seems to offer an interesting technique for obtaining a leukocyte-depleted RCC and FFP.

Blood Cell Count↗
PubMed1995

[Static to sequential plan analysis].

The method of Plan Analysis helps for a better understanding of the interactional engagement of the client within the client-therapist relationship. In spite of this interactional conceptualization of the method, plan analysis produces only a statical diagnosis of interpersonal intentions and plans. In order to realize a dynamical analysis of the client-therapist relationship, the method has to be modified. The steps of this modification will be explained. The result is an idiographic, discovery oriented strategy, called "Sequential Plan Analysis" (SPA), which can be used to do single case analysis of psychotherapy processes. SPA produces sequential patterns of interactional plans (nominal data) as well as quantitative time series.

Adult↗
PubMed1994

The organization of the gene for the functionally dominant alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit GluR-B.

The murine gene encoding the GluR-B subunit of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors was characterized with respect to exon-intron organization, transcriptional start site, alternatively spliced transcripts, and adenosine to guanosine substitutions between gene and complementary DNA sequence. The GluR-B gene spans > 90 kilobase pairs and harbors 17 exons. Transcription appears to initiate approximately 430 nucleotides upstream of the translational start codon, with no intron in the 5'-untranslated region of the gene. Four alternatively spliced mRNAs are generated from the primary GluR-B transcript, two containing the modules Flip and Flop, and another two with alternate C-terminal coding sequence. The major GluR-B mRNAs in murine brain, 4 and 6 kilobase differ in the length of their 3'-untranslated region.

Alternative Splicing↗
PubMed1994

Protein kinase C modulates the insulin secretory process by maintaining a proper function of the beta-cell voltage-activated Ca2+ channels.

In the present study an attempt was made to further elucidate the molecular mechanisms whereby protein kinase C (PKC) modulates the beta-cell stimulus-secretion coupling. Regulation of Ca2+ channel activity, [Ca2+]i, and insulin release were investigated in both normal pancreatic mouse beta-cells and in similar beta-cells deprived of PKC activity. [Ca2+]i was measured with the intracellular fluorescent Ca2+ indicator fura-2 and the Ca2+ channel activity was estimated by the whole cell configuration of the patch-clamp technique. To reveal the various isoenzymes of PKC present in the mouse beta-cell, proteins were separated by one-dimensional gel electrophoresis and Western blotting was performed. The production of inositol phosphates was measured by ion-exchange chromatography and insulin release was measured radioimmunologically. Acute stimulation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate resulted in suppression of both the carbamylcholine-induced increase in [Ca2+]i and production of inositol 1,4,5-trisphosphate. Under these conditions the increase in [Ca2+]i in response to glucose was similar to that found in control cells. When beta-cells were deprived of PKC, by exposure to 200 nM 12-O-tetradecanoylphorbol-13-acetate for 24-48 h, there was an enhanced response to carbamylcholine. This response constituted increases in both the [Ca2+]i signal and production of inositol 1,4,5-trisphosphate. Interestingly, cells with down-regulated PKC activity responded more slowly to glucose stimulation, when comparing the initial increase in [Ca2+]i, than control cells. On the other hand, the maximal increase in [Ca2+]i was similar whether or not PKC was present. Moreover, PKC down-regulated cells exhibited a significant reduction of maximal whole cell Ca2+ currents, a finding that may explain the altered kinetics with regard to the [Ca2+]i increase in response to the sugar. Both the alpha and beta 1 forms of the PKC isoenzymes were present in the mouse beta-cell and were also subjected to PKC down-regulation. Hence, either of these isoenzymes or both may be involved in the modulation of phospholipase C and Ca2+ channel activity. Since insulin release under physiological conditions is critically dependent on Ca(2+)-influx through the voltage-gated L-type Ca2+ channels, the kinetics of hormone release was expected to demonstrate a similar delay as that of the [Ca2+]i increase. Although not as pronounced, such a delay was indeed also observed in the onset of insulin release. There was, however, no effect on the total amounts of hormone released.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Oscillations in cytoplasmic free calcium concentration in human pancreatic islets from subjects with normal and impaired glucose tolerance.

Plasma insulin levels in healthy subjects oscillate and non-insulin-dependent diabetic patients display an irregular pattern of such oscillations. Since an increase in cytoplasmic free Ca2+ concentration ([Ca2+]i) in the pancreatic beta cell is the major stimulus for insulin release, this study was undertaken to investigate the dynamics of electrical activity, [Ca2+]i-changes and insulin release, in stimulated islets from subjects of varying glucose tolerance. In four patients it was possible to investigate more than one of these three parameters. Stimulation of pancreatic islets with glucose and tolbutamide sometimes resulted in the appearance of oscillations in [Ca2+]i, lasting 2-3 min. Such oscillations were observed even in some islets from patients with impaired glucose tolerance. In one islet from a diabetic patient there was no response to glucose, whereas that islet displayed [Ca2+]i-oscillations in response to tolbutamide, suggesting that sulphonylurea treatment can mimic the complex pattern of glucose-induced [Ca2+]i-oscillations. We also, for the first time, made patch-clamp recordings of membrane currents in beta-cells in situ in the islet. Stimulation with glucose and tolbutamide resulted in depolarization and appearance of action potentials. The islet preparations responded to stimulation with a number of different secretagogues with release of insulin. The present study shows that human islets can respond to stimulation with glucose and sulphonylurea with oscillations in [Ca2+]i, which is the signal probably underlying the oscillations in plasma insulin levels observed in healthy subjects. Interestingly, even subjects with impaired glucose tolerance had islets that responded with oscillations in [Ca2+]i upon glucose stimulation, although it is not known to what extent the response of these islets was representative of most islets in these patients.

Aged↗
PubMed1994

The imidazoline derivative calmidazolium inhibits voltage-gated Ca(2+)-channels and insulin release but has no effect on the phospholipase C system in insulin producing RINm5F-cells.

The present study shows that the calmodulin antagonist calmidazolium inhibited influx of Ca2+ through voltage-gated Ca(2+)-channels in clonal insulin producing RINm5F-cells. The mechanism of inhibition may involve both Ca(2+)-calmodulin-dependent protein kinases and direct binding of calmidazolium to the Ca(2+)-channel. Calmidazolium did not affect uptake of Ca2+ into intracellular Ca(2+)-pools, inositol 1,4,5-trisphosphate (InsP3) formation or action on intracellular Ca(2+)-pools. The calmodulin inhibitor also did not affect glucose utilization or oxidation in RINm5F-cells, speaking against an unspecific toxic effect of the compound. KCl-and ATP-stimulated insulin release from RINm5F-cells was attenuated by calmidazolium, whereas basal hormone secretion was unaffected.

Animals↗
PubMed1994

Acute myeloid leukemia (AML-M1) with multiple trisomies and t(8;21)(q22;q22).

Cytogenetic analysis of an acute myeloid leukemia (AML-M1) showed the karyotype 53,XY, +6, +8,t(8;21)(q22;q22), +9, +10, +13, +19, +21. Only one AML with a massively hyperdiploid karyotype (> 50 chromosomes) and t(8;21) has been published before. A comparison of the two cases reveals similarities both with regard to the morphologic subtype (M1) and to which chromosomes were trisomic (+6, +8, +13, +19, and +21 were found in both cases). We surmise that the t(8;21) was the primary chromosomal abnormality and that the set of multiple trisomies occurred secondarily; this pattern of clonal evolution may have favored a more immature leukemic phenotype in these two cases than is regularly seen in t(8;21)-associated leukemias.

Child↗
PubMed1994

Molecular biology of glutamate receptors.

The ligand-gated receptors for L-glutamate play a central role in acute neuronal degeneration. Recently cDNAs have been isolated for subunits of several glutamate receptor subtypes. By sequence homology all these subunits clearly belong to one large gene family. Several subfamilies exist and match roughly previously pharmacologically and electrophysiologically defined subtypes of glutamate receptors. Currently four genes (GluR A, B, C and D) are known that code for the AMPA subtypes of glutamate receptors. Recombinant expression of wild type and mutated sequences identified a critical residue in the putative TM2 channel-lining segment that controls Ca2+ ion permeability. The arginine (R) found in GluR B subunits at that position renders AMPA channels impermeable for Ca2+ ions, whereas glutamine (Q) containing GluR A, C and D subunits give rise to Ca2+ permeable channels. RNA editing converts the genomically encoded glutamine codon into the arginine codon found in GluR B cDNAs for the Q/R site. NMDA subtypes of glutamate receptors are formed after coexpression of the NR1 cDNA with a cDNA of the NR2 family. Depending on the member of the NR2 family used, NMDA receptors with different kinetical and pharmacological properties are generated. Common to all channels of these NMDA receptors is a high permeability for Ca2+ ions and a voltage dependent block by Mg2+ ions. All currently known NMDA receptor subunits have an asparagine at the Q/R homologous position. We found that this residue is critical for Mg2+ block and Ca2+ permeability of NMDA receptor channels.

Amino Acid Sequence↗
PubMed1994

Small N-terminal deletion by splicing in cerebellar alpha 6 subunit abolishes GABAA receptor function.

Sequence variation was found in cDNA coding for the extracellular domain of the rat gamma-aminobutyric acid type A (GABAA) receptor alpha 6 subunit. About 20% of polymerase chain reaction (PCR)-amplified alpha 6 cDNA prepared from rat cerebellar mRNA lacked nucleotides 226-255 as estimated by counting single-stranded phage plaques hybridized specifically to the short (alpha 6S) and long (wild-type) forms of the alpha 6 mRNA. Genomic PCR revealed an intron located upstream of the 30-nucleotide sequence. Both splice forms were detected in the cerebellum by in situ hybridization. Recombinant receptors, resulting from coexpression of the alpha 6S subunit with the GABAA receptor beta 2 and gamma 2 subunits in human embryonic kidney 293 cells, were inactive at binding [3H]muscimol and [3H]Ro 15-4513. In agreement, injection of complementary RNAs encoding the same subunits into Xenopus oocytes produced only weak GABA-induced currents, indistinguishable from those produced by beta 2 gamma 2 receptors. Therefore, the 10 amino acids encoded by the 30-nucleotide fragment may be essential for the correct assembly or folding of the alpha 6 subunit-containing receptors.

Amino Acid Sequence↗
PubMed1994

Comparison of the efficacy and tolerability of moclobemide and maprotiline in depressed patients treated by general practitioners.

We report the results of a multicenter, double-blind study conducted in a general practice setting, in which the efficacy and tolerability of moclobemide, a new antidepressant drug of the reversible inhibitor of monoamine oxidase type A class, were compared with those of maprotiline, a noradrenaline reuptake inhibitor often prescribed in the general practice setting. Participating general practitioners were required to make differential diagnoses of depressive disorders according to DSM-III criteria and then quantitatively assess the efficacy of treatment using the Hamilton Depression Rating Scale (HDRS) and the Zung self-rating depression scale (Zung SDS). One hundred thirty outpatients (mean age 48 years) with major depression according to DSM-III were randomized to receive either moclobemide 300 mg or maprotiline 75 mg daily for 4 weeks. From day 8, dosages were increased if necessary up to a maximum of 400 mg of moclobemide or 100 mg of maprotiline. The results showed that moclobemide was as effective as maprotiline (HDRS, Zung SDS); moclobemide appeared to have the same antidepressant and anxiolytic activity, but a stronger drive-enhancing effect. Moclobemide was the better-tolerated drug, producing fewer side effects than maprotiline did: in particular, fewer instances of somnolence and dry mouth. The good tolerability of the compound was confirmed by the qualitative assessments of the study physicians.

Antidepressive Agents↗
PubMed1994

Nail fold capillaroscopy and echocardiography in mild-to-moderate hypertension treated with cilazapril plus hydrochlorothiazide: first results.

Essential hypertension is characterized by parallel and potentially reversible vascular and cardiac adaptations. In our study, capillaroscopy, echocardiography, and 24-h ambulatory blood pressure profiles were performed in 17 patients (aged 33-63 years; mean, 52 years) with mild-to-moderate hypertension. We measured morphological and hemodynamic parameters of capillary microcirculation as well as morphological echocardiographic parameters at baseline and after 6 weeks' treatment with 5 mg of cilazapril plus 12.5 mg of hydrochlorothiazide. Digital capillary blood flow measurements were assessed by nail fold video capillaroscopy. After 6 weeks of treatment with cilazapril plus hydrochlorothiazide, mean diastolic 24-h ambulatory blood pressure decreased from 98 +/- 6 to 85 +/- 7 mm Hg. Capillary blood cell velocity was 0.6 +/- 0.4 mm/s at baseline and increased to 0.6 +/- 0.4 mm/s. There were no significant changes in morphological capillaroscopic and echocardiographic parameters. In conclusion, we observed a trend toward higher capillary blood cell velocity as early as after 6 weeks of treatment with cilazapril plus hydrochlorothiazide in mild-to-moderate hypertension.

Administration, Oral↗
PubMed1994

Efficacy and tolerability of 5 mg of cilazapril plus 12.5 mg of hydrochlorothiazide in mild-to-moderate hypertension: results of 24-hour ambulatory blood pressure monitoring.

The efficacy and tolerability of a fixed combination of 5 mg of cilazapril and 12.5 mg of hydrochlorothiazide against hypertension was evaluated in 36 patients (26 men and 10 women) between 33-68 years old. Twenty-two had newly diagnosed hypertension and 14 had previously treated hypertension. Twenty-four-hour noninvasive ambulatory blood pressure monitoring (ABPM) was performed after a 2-week washout period. Measurements were taken at 20-min intervals during the day (from 8 a.m. to 10 p.m.) and at 30-min intervals during the night (from 10 p.m. to 8 a.m.). Patients with a mean diastolic daytime pressure of > or = 90 < 115 mg Hg were then given 5 mg of cilazapril plus 12.5 mg of hydrochlorothiazide once daily between 6 a.m. and 8 a.m. for 6 weeks. After this period, a second 24-h ABPM was performed. Office blood pressure measurements were taken at weeks -2, 0, 2, and 6. Routine laboratory blood samples were taken at weeks 0 and 6. Single blood pressure readings did not change significantly during the washout period (between weeks -2 and 0). The ABPM 24-h mean systolic pressure changed between weeks 0-6 from 143 +/- 13 to 126 +/- 11 mm Hg (p < 0.0001), and the mean diastolic pressure from 100 +/- 9 to 90 +/- 9 mm Hg (p < 0.0001). Twenty-eight patients (80) responded to treatment (response criteria: mean diastolic daytime pressure at week 6 < 90 mm Hg and/or a difference between weeks 0-6 > or = 5 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Virus inactivated plasma].

Two different virus inactivated plasma preparations are available in Germany. Methylene blue ephotoxidized (MB) plasma is plasma from a single donation, which is photoxidized using 1 microM methylene blue and visible light (1 hour 60,000 Lux). Photochemical inactivation reduces HIV by at least 5 log10, but also fibrinogen is altered. To date, the clinical significance of this finding is still unclear, since prospective clinical studies are lacking. Solvent detergent (SD) plasma is manufactured from a pool of about 2000 plasma donations, and triton-X-100 and tri-n-butyl-phosphate (TNBP) are added for virus inactivation. HIV and hepatitis viruses are thus reduced by 5 to 6 log10. SD treatment reduces protein S and alpha-2-antiplasmin by about 40%. Clinical studies have already demonstrated, that SD plasma is comparable with untreated, native fresh frozen plasma in terms of efficacy.

Blood Transfusion↗