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Biomedical subjects

T Keller

Publications and source records attributed to T Keller.

At least 37 records · Page 2Linked to original sources
PubMed2000

Tryptophan hydroxylase polymorphisms in suicide victims.

Both environmental and genetic factors appear to contribute to the risk for suicide. The serotonergic system has been implicated in depression, impulsivity and suicidality. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. Suicide has been associated with polymorphisms in intron 7 of the TPH gene. These alleles were studied in samples from 47 deceased Caucasian males as part of the Utah Youth Suicide Study. A 918 base pair fragment spanning the region of interest was amplified. The A218C polymorphism was visualized by restriction fragment length polymorphism (RFLP) and the A779C was sequenced. Neither A218C nor A779C appeared to be associated with suicide in this population. These results did not change when the sample was stratified by age (10-21 years, 22-31 years) or when violent suicides were selected. The complexity of the phenotype of suicide may reflect multiple biological and social etiologic factors, and poses a worthy challenge for genetic studies.

Adolescent↗
PubMed2000

Fluorescence polarization immunoassay for the detection of drugs of abuse in human whole blood.

Fluorescence polarization immunoassay (FPIA) is a technique which has been known for a number of years. Since the development of the fundamental principles of fluorescence polarization by Perrin in a series of papers beginning in 1926, immunological techniques using labelled reactants have gained an extraordinary importance in the field of medical research and in routine diagnosis. As one of the non-radioactive immunological techniques, FPIA has found broad application in clinical and forensic toxicology. The authors report a new method to quickly screen autopsy, police and hospital blood samples for opiates, benzodiazepines, benzoylecgonine, barbiturates and methadone after Extrelut extraction utilising the FPIA methodology.

Anti-Anxiety Agents↗
PubMed2000

Endogenous patterns of TGFbeta superfamily signaling during early Xenopus development.

Transforming growth factor beta (TGFbeta) superfamily signaling has been implicated in patterning of the early Xenopus embryo. Upon ligand stimulation, TGFbeta receptors phosphorylate Smad proteins at carboxy-terminal SS(V/M)S consensus motifs. Smads 1/5/8, activated by bone morphogenetic protein (BMP) signaling, induce ventral mesoderm whereas Smad2, activated by activin-like ligands, induces dorsal mesoderm. Although ectopic expression studies are consistent with roles for TGFbeta signals in early Xenopus embryogenesis, when and where BMP and activin-like signaling pathways are active endogenously has not been directly examined. In this study, we investigate the temporal and spatial activation of TGFbeta superfamily signaling in early Xenopus development by using antibodies specific for the type I receptor-phosphorylated forms of Smad1/5/8 and Smad2. We find that Smad1/5/8 and two distinct isoforms of Smad2, full-length Smad2 and Smad2(delta)exon3, are phosphorylated in early embryos. Both Smad1/5/8 and Smad2/Smad2(delta)exon3 are activated after, but not before, the mid-blastula transition (MBT). Endogenous activation of Smad2/Smad2(delta)exon3 requires zygotic transcription, while Smad1/5/8 activation at MBT appears to involve transcription-independent regulation. We also find that the competence of embryonic cells to respond to TGF(delta) superfamily ligands is temporally regulated and may be a determinant of early patterning. Levels of phospho-Smad1/5/8 and of phospho-Smad2/Smad2(delta)exon3 are asymmetrically distributed across both the animal-vegetal and dorsoventral axes. The timing of the development of these asymmetries differs for phospho-Smad1/5/8 and for phospho-Smad2/Smad2(delta)exon3, and the spatial distribution of phosphorylation of each Smad changes dramatically as gastrulation begins. We discuss the implications of our results for endogenous functions of BMP and activin-like signals as candidate morphogens regulating primary germ layer formation and dorsoventral patterning of the early Xenopus embryo.

Amanitins↗
PubMed1999

GC/MS determination of zolpidem in postmortem specimens in a voluntary intoxication.

An ingestion of an unknown quantity of Ivadal (zolpidem) tablets in a case of drug abuse is described. The authors report a new and fast method of analysing and determining the zolpidem concentration in postmortem specimens. Quantitation of zolpidem was performed by ethyl acetate extraction from alkalinized body fluids before GC/MS analysis. The analyses were performed without any complex sample clean-up steps and with little sample material. Postmortem concentrations of zolpidem in body fluids are given. The proposed method is a rapid procedure of analysis in cases of deliberate poisoning with the sedative-hypnotic drug, zolpidem.

Alcoholism↗
PubMed1999

Determination of ethyl glucuronide, a minor metabolite of ethanol, in human serum by liquid chromatography-electrospray ionization mass spectrometry.

A rapid and sensitive determination procedure using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) has been developed for the determination of ethyl glucuronide (EtG) in human serum. Samples were precipitated with methanol, centrifuged and the supernatant was evaporated to dryness followed by reconstitution with distilled water. As mobile phase 30 mM ammonium acetate-acetonitrile (30:70, v/v) was utilized. The base peak observed at m/z 221 was the [M-H]- ion of EtG, which was detectable in satisfactory sense. The detection limit was 0.03 microg/ml in the selected ion monitoring mode. A calibration graph constructed for EtG in serum gave good linearity over the range from 0.1 to 25 microg/ml. This paper also presents the application of this LC-ESI-MS procedure to the analysis of authentic serum samples.

Alcohol Drinking↗
PubMed1999

Analysis of psilocybin and psilocin in Psilocybe subcubensis Guzmán by ion mobility spectrometry and gas chromatography-mass spectrometry.

A new method has been developed for the rapid analysis of psilocybin and/or psilocin in fungus material using ion mobility spectrometry. Quantitative analysis was performed by gas chromatography-mass spectrometry after a simple one-step extraction involving homogenization of the dried fruit bodies of fungi in chloroform and derivatization with MSTFA. The proposed methods resulted in rapid procedures useful in analyzing psychotropic fungi for psilocybin and psilocin.

Agaricales↗
PubMed1999

Effects of L-carnitine and its acetyl and propionyl esters on ATP and PCr levels of isolated rat hearts perfused without fatty acids and investigated by means of 31P-NMR spectroscopy.

31P-NMR in vivo spectroscopy is a non-invasive and non-hazardous technique which investigates chemical composition and metabolism of living objects, for example by determining phosphocreatine (PCr) and ATP concentrations. In the present study we investigated the influence of L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine on the energetic state of the Langendorff rat heart subjected to an ischemic period of 20 min followed by a reperfusion period of 60 min. To avoid an overlapping of the effects of fatty acids and glucose, the hearts were perfused with a Tyrode solution containing no fatty acids. Ischemia causes a rapid decrease in the PCr signal, followed by a decrease in the ATP signal after a prolonged period of ischemia. At the same time, a drastic increase in the Pi signal was observed. A partial recovery of the ATP and PCr signals was observed in the reperfusion period. With L-carnitine a markedly improved recovery of the high energy phosphates (e.g. increased PCr/P ratios) was found. With acetyl-L-carnitine this effect was enhanced in the first postischemic phase. It was followed, however, by a more rapid decrease in the PCr/Pi ratio in the late reperfusion period. The effect of propionyl-L-carnitine was not significantly improved in the first minutes of the reperfusion period, but during the whole reperfusion phase a stabilization of the PCr/Pi ratio was observed. Intracellular pH can be calculated from determination of the Pi-chemical shift. This shows that L-carnitine and its derivatives have a protective effect against intracellular pH decrease during ischemia. L-carnitine improves the energetic state of the heart, which leads to increased ischemia tolerance. Hearts under L-carnitine were able to tolerate up to four ischemia-reperfusion periods in succession, whereas the controls were not able to do so. These NMR results confirm the hypothesis that L-carnitine and its esters have a protective effect in the reperfusion period of the ischemic rat heart. This could be of importance for the treatment of ischemic cardiac diseases.

Acetylcarnitine↗
PubMed1999

The real incidence of percutaneous injuries in the operating room--a prospective study.

Despite the frequent exposure of operating room personnel to blood and other body fluids and the obvious risk of occupational transmission of HIV infection, the real incidence of injuries after needle sticks or cuts in the operating room has not been well investigated. Every injury occurring in the operating room during one thousand consecutive elective and emergency procedures was studied and the risk for acquiring an HIV infection was calculated. There were 50 injuries during 761 elective procedures (6.6%) and 23 injuries during 239 emergency operations (9.6%). There was one single injury during 91 minimally invasive endoscopical procedures (1.1%). The surgeon was the person most frequently injured (3.5%). The injury rate of the scrub nurse varied between 1.4% and 2.8% according to the surgeon's experience. The operating room personnel is at risk for an occupational transmission of blood born pathogens. If the seroprevalence of HIV in surgical patients is estimated at 0.4% the calculated probability for a surgeon to acquire HIV infection over a 30-year career amounts to 0.3%.

Accidents, Occupational↗
PubMed1999

A pilot trial of GM-CSF and MDX-H210 in patients with erbB-2-positive advanced malignancies.

MDX-H210 is a chemically, cross-linked, half-humanized bispecific antibody composed of F(ab') fragment from monoclonal antibody (mAb) H22 that binds to the high-affinity receptor Fc gamma RI and F(ab') of mAb 520C9 that recognizes the erbB-2 (HER2/neu) oncoprotein. In a previous trial, the murine bispecific, MDX-210 at a dose of 7 mg/m2, was well tolerated and activated monocytes and macrophages in vivo in doses as low as 0.35 mg/m2. In our multidose trial, granulocyte-macrophage colony-stimulating factor, which increases and activates potential effector cells, was given on days 1-4 at 250 micrograms/m2 s.c. and MDX-H210 was given on day 4 weekly for 4 consecutive weeks. Thirteen patients were treated at dose levels of 1, 3.5, 7, 10, 15, and 20 mg/m2 without dose-limiting toxicity. Fever, chills, and rigors occurred during and up to 2 h postinfusion and correlated with the time to peak levels of tumor necrosis factor-alpha (median 88.2 pg/ml; range 15.6-887 pg/ml) and interleukin-6 (median 371 pg/ml; range 175-2,149 pg/ml). By the fourth consecutive week of treatment the side effects and cytokine levels decreased significantly. Human antibispecific antibody (HABA) levels were increased by 200- to 500-fold above pretreatment levels in 5 of 11 evaluable patients after 3 weeks of treatment. The monocyte and granulocyte population increased on days 4 and 11 (median 44%; range 18-68% and 42%; 19-71%), respectively, for monocytes and (60%; 43-75% and 74%; 54-82%) on days 4 and 11 for granulocytes. There was a significant decrease in the monocyte populations immediately after MDX-H210 administration (median decrease 73%; range 42-94%) and (52%; 12-72%) on days 4 and 11, respectively. Ten patients completed 4 weeks of treatment. One patient had a 48% reduction in an index lesions and six patients had stable disease at the time of evaluation. Three patients progressed before the fourth week. The therapy was generally well tolerated with toxicity, primarily, limited to the days of treatment.

Adenocarcinoma↗
PubMed1999

Follow-up in prostate cancer patients: which parameters are necessary?

AIM: In a retrospective study we examined whether follow-up of prostate cancer (PC) patients can be managed by using prostate-specific antigen (PSA) as a unique tool as postulated recently. PATIENTS AND METHODS: According to strict criteria established in the eighties, at our institution PC patients were monitored by PSA, prostatic acid phosphatase (PAP), alkaline phosphatase (AP), digital-rectal examination, renal and bladder ultrasound every 3 months, abdominopelvic computerized tomography (CT) and bone scan every 6 months. Between 1988 and 1994, 80 patients with PC cancer were eligible (mean follow-up 29.5, range 12-81 months). Patients were categorized into 4 groups: localized tumor (n = 44); lymph node metastases (n = 9); distant metastases (n = 18), and lymph node and distant metastases (n = 9). The parameters mentioned were compared for the assessment of progression, regression and stabilization of the disease. RESULTS: Our examinations showed that PSA is superior to all the other parameters used. In all groups, there were no patients with progressive disease detected by PAP, AP, CT and bone scan, but not by PSA. PSA anticipated the other parameters in detecting progression by several months. Renal ultrasound, however, detected new hydronephrosis in 6 patients with stable or decreasing PSA. Hydronephrosis was caused by surgery or radiotherapy, not by progressive PC. CONCLUSION: PSA can be used as a unique tool in the follow-up of PC patients in all stages. However, patients who underwent therapy potentially afflicting the urinary tract should have additional renal and bladder ultrasound.

Acid Phosphatase↗
PubMed1998

Fatal chloroquine intoxication.

A suicidal ingestion of an unknown quantity of Resochin (chloroquine) tablets is described. Although chloroquine is known since 1934, intoxications due to chloroquine overdose are rather rare in European countries. The authors report on a new and fast method of analysing and determining the chloroquine concentration in body fluids and postmortem specimens. The analytes were extracted from alkalinized samples into ethyl acetate before GC/MS analysis. The analyses of chloroquine were performed without any complex sample clean-up steps and, in addition, with little sample material. The proposed method resulted in a rapid procedure most useful in cases of deliberate poisoning with the anti-inflammatory and antimalarial drug chloroquine.

Adult↗
PubMed1998

Detection of designer drugs in human hair by ion mobility spectrometry (IMS).

Since its inception in the early 1970s under the name plasma chromatography, ion mobility spectrometry (IMS) has undergone great changes. It is now utilized more and more in forensic science laboratories where it is used to detect explosives and environmental pollutants [1-4] as well as its use in detecting drugs of abuse [5-8]. Although IMS is known for nearly 30 years now [9], relatively few cases of the application of ion mobility spectrometry to the analysis of human hair have been reported [10-12]. The authors report a new and quick method to rapidly screen and determine MDMA ('ecstasy', 'Adam') and MDEA ('Eve') in human hair. The proposed method using trihexylamine as internal standard resulted in a rapid procedure useful in screening human hair specimens for designer drugs.

3,4-Methylenedioxyamphetamine↗
PubMed1998

Tumour markers in the diagnosis of bronchial carcinoma: new options using fuzzy logic-based tumour marker profiles.

The diagnosis of lung cancer and early knowledge of its histological type are very important; however, this is still a difficult subject for the physician. The aim of this study was to improve the diagnostic efficiency of tumour markers in the diagnosis of bronchial carcinoma by mathematical evaluation of a tumour marker profile employing fuzzy logic modeling. A panel of five tumour markers, including CYFRA 21-1, CEA, NSE, and five additional parameters was determined in 281 patients with confirmed primary diagnosis of bronchial carcinoma of different histology and stage. A further 131 persons, who had acute and chronic benign lung diseases, served as a control group. A classificator was developed using a fuzzy-logic rule-based system. The diagnostic value of the combined tumour markers was significantly better than that of the individual markers and of a combination of CYFRA 21-1, CEA, and NSE. The discrimination of malignant vs benign diseases was realized with a sensitivity of 87.5% and specificity of 85.5%. The rate of correct classification of small-cell vs non-small-cell lung carcinoma was 90.6% and 91.1%, respectively; for squamous cell carcinoma vs adenocarcinoma it was 76.8% and 78.8%, respectively. Our detailed analysis has shown that the fuzzy logic system improves diagnostic accuracy up to a rate of 20%, especially in early stages and in patients with all marker levels in the grey area. Our concept proved to be more powerful than measurement of single markers or the combination of CEA, CYFRA 21-1, and NSE. Its use may help in distinguishing between malignant and benign disease and make it possible to define different subgroups of patients earlier in the course of their disease.

Adolescent↗
PubMed1998

Structural analysis of the amplified IFN-beta and DHFR genes in a Chinese hamster ovary cell line using multicolour FISH analysis.

Multicolour FISH was used to get insight into the structural arrangement of a homogeneously staining region which bears the co-transfected and subsequently co-amplified IFN-beta and DHFR genes in a CHO cell line. On metaphase chromosomes an arrangement of multiple bands with regular spacing is revealed. On extended chromatin fibres a cluster of directly repeated and interspersed IFN-beta and DHFR genes is visible. Up to three clusters were found arranged in tandem. The different chromosomal mechanisms leading to gene amplification are discussed.

Animals↗
PubMed1998

The effect of sealing and of additives on the fermentation characteristics and mould and yeast counts in stretch film wrapped big-bale lucerne silage.

The effect of number of film layers was investigated in silages produced in wrapped big bales. The herbage used was difficult to ensile lucerne wilted to DM levels of 320-490 g/kg. Fermentation changed to a more homofermentative process as the number of film layers increased. An increasing number of film layers (4, 6, 8 or 10) also resulted in a notable decrease in moulds and yeasts. Four layers could not guarantee successful preservation in lucerne, and higher numbers of undesirable micro-organisms were detected. Hard stalks damaged the first two film layers during wrapping in the bales. Effect of number of film layers was more important than effect of additives for inhibition of mould and yeast counts.

Fermentation↗
PubMed1998

A plant homolog of the neutrophil NADPH oxidase gp91phox subunit gene encodes a plasma membrane protein with Ca2+ binding motifs.

Rapid generation of O2- and H2O2, which is reminiscent of the oxidative burst in neutrophils, is a central component of the resistance response of plants to pathogen challenge. Here, we report that the Arabidopsis rbohA (for respiratory burst oxidase homolog A) gene encodes a putative 108-kD protein, with a C-terminal region that shows pronounced similarity to the 69-kD apoprotein of the gp91phox subunit of the neutrophil respiratory burst NADPH oxidase. The RbohA protein has a large hydrophilic N-terminal domain that is not present in gp91phox. This domain contains two Ca2+ binding EF hand motifs and has extended similarity to the human RanGTPase-activating protein 1. rbohA, which is a member of a divergent gene family, generates transcripts of 3.6 and 4.0 kb that differ only in their polyadenylation sites. rbohA transcripts are most abundant in roots, with weaker expression in aerial organs and seedlings. Antibodies raised against a peptide near the RbohA C terminus detected a 105-kD protein that, unlike gp91phox, does not appear to be highly glycosylated. Cell fractionation, two-phase partitioning, and detergent extraction indicate that RbohA is an intrinsic plasma membrane protein. We propose that plants have a plasma membrane enzyme similar to the neutrophil NADPH oxidase but with novel potential regulatory mechanisms for Ca2+ and G protein stimulation of O2- and H2O2 production at the cell surface.

Amino Acid Sequence↗
PubMed1998

The economics of TRACE. A cost-effectiveness analysis of trandolapril in postinfarction patients with left ventricular dysfunction.

OBJECTIVE: The objective of the study was to compute a cost-effectiveness ratio relating the economic cost of trandolapril to the number of effectiveness units (i.e. life-years) gained. DESIGN AND SETTING: The trandolapril cardiac evaluation (TRACE) study was a prospective placebo-controlled clinical trial designed to determine the long term effect of the oral angiotensin-converting enzyme (ACE) inhibitor trandolapril in postinfarction patients with left ventricular dysfunction. We used the individual data of the TRACE trial to compute a cost-effectiveness ratio relating the economic cost of trandolapril to the number of life-years saved. The analysis was differential and was conducted from a payer perspective in a French setting. Costs were computed from individual data related to the use of resources during the TRACE trial. For drug treatments, we chose French public prices, and for hospitalisations, we used the mean cost as determined by the diagnosis related group (DRG) from the 1996 Programme de Médicalisation des Systémes d'Information (PMSI) database from the French Ministry of Health. Life expectancy was estimated through an accelerated failure-time model with an exponential distribution specification; we made the conservative hypothesis that the effect of trandolapril on mortality after the end of the trial was nil. We assessed the standard deviation and the 95% confidence interval (CI) of the ratio through its bootstrap distribution. RESULTS: The incremental cost-effectiveness ratio of treating patients with trandolapril rather than with placebo was estimated as 4910 French francs (FF) per life-year saved. Discounting both costs and health effects led to ratio of FF6950 per life-year saved. The bootstrap estimate of the ratio reached FF5950 and the 95% CI was FF5650 to FF6250 per life-year saved. CONCLUSIONS: These results could be considered as highly cost effective, even though our estimation was very close to the design and the conditions of the TRACE trial. Nevertheless, we showed that this trial constitutes a favourable case for economic evaluation.

Aged↗