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Biomedical subjects

P Kessler

Publications and source records attributed to P Kessler.

At least 109 records · Page 6Linked to original sources
PubMed1996

Etomidate and thiopental inhibit the release of endothelium-derived hyperpolarizing factor in the human renal artery.

BACKGROUND: Endothelium-derived hyperpolarizing factor is thought to be a cytochrome P450-derived arachidonic acid metabolite that hyperpolarizes vascular smooth muscle cells by opening Ca(2+)-activated K+ channels (K+Ca channels). In the rabbit carotid artery both volatile and intravenous anesthetics inhibit the acetylcholine-stimulated release of endothelium-derived hyperpolarizing factor. Because the release of this factor may help to maintain vascular tone in humans under conditions of a failing nitric oxide synthesis, e.g., in atherosclerosis, the effects of two intravenous anesthetics, thiopental and etomidate, on the endothelium-derived hyperpolarizing factor-mediated relaxant response to acetylcholine were investigated in human isolated renal artery segments. METHODS: The segments were suspended in Krebs-Henseleit solution (37 degrees C) containing the cyclooxygenase inhibitor diclofenac (1 microM) and preconstricted with norepinephrine (6 microM). Relaxations caused by acetylcholine (1 microM) were compared in the presence and absence of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine (0.1 mM) in control segments and in segments exposed to etomidate or thiopental (0.03-0.3 mM). In addition, the effects of the two anesthetics on the relaxant response to the nitric oxide donors glyceryl trinitrate (3 microM) and sodium nitroprusside (0.1 microM) were examined. RESULTS: The relaxant response to acetylcholine, which was resistant to both nitric oxide synthase and cyclooxygenase blockade, was markedly reduced by the K+Ca channel antagonist tetrabutyl ammonium (3 mM) and the cytochrome P450 inhibitor clotrimazole (30 microM). Both etomidate and thiopental, at a concentration of 0.3 mM, selectively attenuated the relaxant response to acetylcholine in N(G)-nitro-L-arginine-treated segments, but did not affect relaxations elicited by glyceryl trinitrate or sodium nitroprusside. CONCLUSIONS: Etomidate and thiopental inhibit the endothelium-derived hyperpolarizing factor-mediated relaxant response to acetylcholine in the human renal artery, an effect that appears to be attributable to the cytochrome P450-inhibiting properties of these anesthetics.

Anesthetics, Intravenous↗
PubMed1995

Polymerase chain reaction detection of the BCR-ABL fusion transcript after allogeneic marrow transplantation for chronic myeloid leukemia: results and implications in 346 patients.

We studied 346 patients after bone marrow transplantation (BMT) for chronic myeloid leukemia (CML) for the presence of the bcr-abl transcript detected by the polymerase chain reaction (PCR) to understand the frequency and implication of a positive test. A total of 634 samples of BM and/or peripheral blood were obtained for PCR analysis between 3 and 192 months after BMT. A positive PCR test at 3 months post-BMT was not statistically significantly associated with an increased risk of relapse compared with PCR-negative patients. However, a positive PCR assay at 6 months and beyond was highly associated with subsequent relapse. The Kaplan-Meier estimate of relapse for patients testing PCR-positive at 6 to 12 months was 42% versus 3% for PCR-negative patients (P < .0001). The Kaplan-Meier estimate of survival at 4 years for the PCR-positive patients was 74% compared with 83% for the PCR-negative group (P = .002). Multivariable analysis indicated that a PCR-positive result at 6 to 12 months post-BMT, the type of BMT donor (allogeneic matched donor v mismatched or unrelated), and the presence of acute GVHD were independent risk factors for subsequent relapse. The relative risk (RR) for relapse for patients PCR-positive at 6 to 12 months post-BMT was 26.1 (95% confidence interval, 8.9 to 76.1, P < .0001). The outcome of long-term patients (> 36 months post-BMT) who tested PCR-positive was much better, as 15 of 59 (25%) tested positive for bcr-abl, but only one patient relapsed. There was a 91% concordance between PCR tests of simultaneously obtained BM and peripheral blood. These analyses show that the PCR assay of the bcr-abl fusion transcript 6 to 12 months post-BMT is an independent predictor of subsequent relapse which provides an opportunity for early therapeutic intervention.

Adolescent↗
PubMed1995

Site-directed disulfide reduction using an affinity reagent: application on the nicotinic acetylcholine receptor.

The aim of this study was to present a new concept of site-directed reduction of disulfide bonds based upon the use of an affinity ligand harbouring a readily oxidizable dithiol. The cysteine bond involved in the acetylcholine binding site of the AChoR was specifically reduced by a carbamylcholine analogue. The ligand, in its oxidized form, was characterized by an affinity constant of 20 microM for the agonist binding site. In its dithiol form, it specifically reduced the disulfide between Cys-192 and Cys-193 on the alpha-subunits of the nicotinic acetylcholine receptor. This reduction needed 10 times lower concentration when carried out with site-directed reducing agent (ARA) than with DTT, and was highly specific for the alpha-subunits. The contribution of the carbamylcholine moiety of the site-directed reducing agent was clearly demonstrated in kinetic studies where reduction abilities of ARA, DTT and the methylated analogue of ARA (MeRA) were compared. At the same concentration (20 microM), DTT and MeRA had a 25 times lower initial rate of reduction than ARA. With 200 microM of DTT this initial reduction was still 4 times lower. Furthermore, the use of a maleimido undecagold cluster which specifically labeled the reduced nicotinic receptor opens the way to structural analysis of the agonist binding site by electron microscopy. These results demonstrate the potency of this kind of site-directed reducing agent for structural study of receptors or enzymes involving a disulfide bond in their active site.

Affinity Labels↗
PubMed1994

Automatic reduction of NMR spectroscopic data for statistical and pattern recognition classification of samples.

A general method of automatically reducing NMR spectra to provide numerical descriptors of samples has been developed and investigated. These descriptors can be used as input to pattern recognition or multivariate algorithms for sample classification. The methods have been tested using 600 MHz one-dimensional 1H NMR spectra of biofluids which are complex mixtures. The approach is, in principle, applicable to multidimensional and heteronuclear NMR spectra and to other types of liquid samples such as oils and foodstuffs as well as to situations such as 1H or 31P NMR in vivo and solid state NMR in drug formulation analysis. The method relies upon apportioning the information in the spectra to individual contiguous segments and allowing specified regions of the spectra to be omitted. Three approaches, based on the number of peaks, the summed peak heights and the summed peak areas respectively in each segment, have been tested. The effect of segment width and overlap and the effects of manipulation of the NMR spectra have been evaluated in terms of the classification of the samples using principal components analysis. A simple method of generating NMR based spectral descriptors for object classification is thus proposed.

Algorithms↗
PubMed1994

Prolongation of the QT-interval during induction of anesthesia in patients with coronary artery disease.

During induction of anesthesia in 60 patients undergoing coronary artery bypass grafting (CABG), we measured the QT-interval (QTI) in the ECG, heart rate (HR) and mean arterial pressure (MAP). Based on the HR, we corrected the QT-interval (QTcI). Prior to induction, six patients (10%) already had abnormal prolongation of QTcI (> or = 440 ms). After injection of fentanyl and vecuronium, the QTcI increased significantly (P < 0.01); to a far lesser extent after injection of hypnotics (i.e. etomidate, midazolam or propofol). Orotracheal intubation caused significant shortening of QTcI (P < 0.01). HR decreased markedly after injection of fentanyl. MAP decreased, however, only after injection of hypnotics. In the immediate post intubation period, HR and MAP increased significantly. The various hypnotics produced no significant difference in HR and QTcI at any measurement point. MAP changed only after injection of hypnotics. The decrease of HR and MAP during induction of anesthesia is thought to result from a corresponding reduction of adrenosympathetic stimulation. We believe that QTcI is similarly influenced.

Anesthesia, Intravenous↗
PubMed1994

Detection of BCR-ABL fusion genes in adult acute lymphoblastic leukemia by the polymerase chain reaction.

The sensitivity and clinical utility of the polymerase chain reaction (PCR) assay for the detection of BCR-ABL gene rearrangement was compared to conventional cytogenetics for the Philadelphia chromosome (Ph1) in adult acute lymphoblastic leukemia (ALL) patients entered onto a single clinical trial. Ninety-three patients had evaluable PCR assays for both the p190bcr-abl and p210bcr-abl type of BCR-ABL gene rearrangements. Twenty-one of 93 patients (23%) were positive for the BCR-ABL rearrangement by the PCR assay. Fourteen of these patients had the p210brc-abl BCR-ABL rearrangement characteristically seen in CML patients, while seven had the p190bcr-abl rearrangement seen in ALL alone. Of 61 patients analyzed, both with conventional cytogenetics and PCR, eight (13%) were positive for the Ph1, while 14 (23%) were positive for the BCR-ABL rearrangement by the PCR assay. Discordance between the PCR assay and cytogenetics occurred in eight cases where the PCR assay was positive and the cytogenetics negative, and two cases where the PCR assay was negative and cytogenetics positive. PCR positivity did not correlate with treatment response, survival, or relapse-free survival, but there was a higher percentage of L2 FAB morphology in the PCR+ cases compared to the PCR-cases (67 vs. 28%, p = 0.003). In addition, the data suggested that patients with a p190bcr-abl rearrangement have a better response to induction therapy, but a worse relapse-free survival compared to patients with a p210bcr-abl breakpoint, but these differences were not statistically significant. These data suggest that PCR and conventional cytogenetics may provide complementary information, since there appear to be a subset of patients who are Ph1-negative yet BCR-ABL positive by PCR. Further studies will be required to determine the prognostic significance of the detailed information about BCR-ABL breakpoints that is available from the PCR assay.

Adolescent↗
PubMed1994

[Changes in hemocoagulation during thrombolytic therapy of acute myocardial infarct in relation to risks of thrombotic complications].

In 38 patients with acute myocardial infarction treated with 1.5 million u. of streptokinase hemocoagulation parameters were assessed before and after treatment and after another 12, 24 and 48 hours. The authors revealed three risk indicators of thrombotic complications: 1. a shortened aPTT before treatment and at the same time a less than double prolongation of aPTT, as compared with control plasma after treatment (P < 0.01, sensitivity 0.67, specificity 0.81). 2. A non-detectable fibrinogen level (less than 1.1 milligrams) 24 hours after termination of treatment (P < 0.05, sensitivity 0.59, specificity 0.71). 3. The third risk factor 3 is a combination of the previous two: shortened aPTT before treatment and at the same time its inadequate prolongation after treatment and/or an undetectable fibrinogen level 24 hours after treatment (P < 0.001, sensitivity 1.00, specificity 0.57). In all the authors' patients with thrombotic complications (reinfarction, recurrent myocardial ischaemia, extended infarction, intracardiac thrombosis, embolization into the CNS) this 3rd combined risk factor was positive.

Female↗
PubMed1993

[ST segment changes in the ECG. Anesthesia induction with propofol, etomidate or midazolam in patients with coronary heart disease].

Induction of anaesthesia with propofol and fentanyl can lead to marked reductions in mean arterial pressure (MAP) and heart rate (HR). Thus, the application of propofol in patients with severely reduced coronary artery perfusion is controversial. METHODS. The study group consisted of 60 patients undergoing coronary artery bypass grafting (CABG). Anaesthesia was induced over 30 s with propofol (P 1.5 mg/kg), etomidate (E 0.3 mg/kg), or midazolam (M 0.15 mg/kg) following a bolus dose of fentanyl (5 micrograms/kg). Vecuronium was used as a muscle relaxant. During induction we continuously measured MAP and HR and recorded the occurrence of myocardial ischaemia using an automatic ST-segment analyser (Marquette 7010). ST-segment deviations of more than 1 mm in leads II and V5 were interpreted as significant signs of myocardial ischaemia. RESULTS. All groups showed reductions in MAP and HR on induction that were marked in the P group. Intubation caused elevation of MAP and HR to pre-induction levels (HR: all groups) or slightly above (MAP: E, M). Four patients in the P group and 3 in each other group showed significant ST-segment deviation prior to induction. In the P group these deviations disappeared in 2 patients after injection while they remained unchanged in the M group. In the E group injection had no effect on the ischaemic ECG changes but produced another case of significant ST-segment deviation. Laryngoscopy and intubation produced no further significant ST-segment deviation in either group. DISCUSSION. Induction is a critical phase of anaesthesia, especially in patients with limited coronary reserve. Induction agents should alleviate the stress response while causing minimal haemodynamic changes. Despite marked reductions in MAP in the P group, the number of patients with ischaemic ECG changes was cut by half. Their number was unchanged or even raised in the other groups. After application of P, with an alleged reduction of coronary perfusion, a compensational reduction in myocardial oxygen consumption may occur.

Aged↗
PubMed1992

[Fiberoptic intubation as a safe method for the treatment of odontogenic abscesses].

Infections caused by dental disease may result in severe swelling of the throat and whole neck. In an operation for opening an abscess, the initial phase of general anaesthesia is often critical due to obstructions of the airway and trismus. Therefore the wide use of a fibre-optic intubation is advocated in order to avoid an emergency tracheostomy or other complications.

Airway Obstruction↗
PubMed1992

[Thrombolysis of arterial retinal occlusion using urokinase].

The authors present an account on possible aimed thrombolytic treatment of occlusion of the retinal artery by urokinase. Aimed thrombolysis can be performed at ophthalmological departments with an available radiodiagnostic department, which performs angiographies of carotid arteries. The authors discuss the necessary dose of 200,000 to 300,000 i.u. of urokinase. One-hour infusion with an initial booster dose is best. Early administration of the preparation is considered most important by the authors. The authors present the case-history of a 34-year-old patient with complete occlusion of the central retinal artery with haemodynamically severe aortal stenosis with a congenital background. Urokinase was administered six hours after occlusion of the artery. Gradually reperfusion of the retina occurred and improvement of the visual acuity from 0.01 to 0.17 with a residual relative wedge-shaped loss of the visual field and paleness of the disc of the optic nerve.

Adult↗
PubMed1991

[A mortality study in the Internal Medicine Emergency Service of October 12 Hospital during 1989].

152,902 patients were attended at the Emergency Department of "12 de Octubre" Hospital during 1989; 48,701 of them were seen in the Internal Medicine area. 196 dead, 164 case histories were selected in order to fulfil the protocol. Several variants were analysed, such as age, sex, diagnosis, time spent at the hospital, quality of life, date, etc. 53.6% were male; the median age was 73 years and the overall median age of all patients seen was 55.9 years. Median Karnovsky was 52.50% of the patients died during their first 5 hours at the Emergency Department. The most frequent diagnoses for the area were neurological, followed by cardiovascular, oncological, digestive, etc. The most frequent diseases observed were cerebrovascular accident, cardiac insufficiency and acute infarction, oncological cases and death on arrival. Mortality was higher in winter. On the whole, mortality was higher in oncology patients followed way behind by neurology digestive and cardiovascular patients.

Age Factors↗