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J Metzger

Publications and source records attributed to J Metzger.

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

Ethyl glucuronide: a marker of recent alcohol consumption with clinical and forensic implications.

A marker with a specific time spectrum of detection and both high sensitivity and specificity is required to diminish the clinically as well as forensically important gap on the time axis between short- and long-term markers of alcohol consumption like ethanol and CDT, GGT or MCV, respectively. Ethyl glucuronide (EtG) is a non-volatile, water-soluble, stable upon storage, direct metabolite of ethanol with a molecular weight of 222 g/mol that can be detected in body fluids for an extended time period after the complete elimination of alcohol from the body. We investigated 107 urine and 78 serum samples of a total of 107 inpatients in 4 groups: (1) 33 inpatients in acute alcohol withdrawal and long term treatment; (2/3) 29 and 15 addicted forensic psychiatric inpatients (#64 StGB, penal code); (4) 30 recently detoxified inpatients of a station for long term treatment by LC/MS-MS with the internal standard d5-EtG and additionally in the fourth group of patients also by gas chromatography/mass spectrometry (GC/MS). In 2 out of 33 inpatients of the first group, EtG could be determined 3 days after hospitalization; in an other subject, a relapse could be detected. In 2 out of 29 and in 1 out of 15 forensic inpatients of group 2 and 3, respectively--where neither clinical impression nor routine laboratory findings gave an indication for relapse--concentrations of EtG ranged between 0.1 and 18 mg/l in urine. For the serum samples of the 30 inpatients of group 4, we could demonstrate a total agreement for the results of the GC/MS and the LC/MS-MS method as to whether a sample was found to be positive or negative for EtG. We suggest that these results strengthen our earlier findings that ethyl glucuronide is a marker of alcohol consumption in general that can be detected for an extended time period after the complete elimination of alcohol from the body and a marker for relapse control with a specific time frame of detection intermediate between short- and long-term markers.

Adult↗
PubMed2000

[The Advanced Breast Biopsy Instrumentation (ABBI) for evaluation of mammographically suspicious, non-palpable findings of the breast: a reliable diagnosis with minor therapeutic potential].

BACKGROUND: Stereotactic biopsy techniques supersede conventional hook-wire localization followed by open excision to clarify the dignity of nonpalpable mammographic lesions. The advanced breast biopsy instrumentation (ABBI) allows stereotactically guided excision of a specimen up to 20 mm in diameter on an outpatient basis under local anaesthesia. METHODS: Demographic information, mammographic and pathological findings, complications, subsequent interventions and sensitivity as well as efficiency of a series of 144 planned ABBI procedures were documented (largest published single institution series). RESULTS: The ABBI procedure was successfully performed in 93.8% (135/144); accurate diagnosis was made in 99.3% (134/135), sensitivity for malignant lesions was 96.9% (31/32) and morbidity was 1.5%. Consistent with other published series margins of the biopsy cylinder containing a malignant lesion were involved in 83.9% (26/31). CONCLUSIONS: Excisional biopsy using the ABBI system is a reliable diagnostic tool with a low incidence of morbidity. The therapeutic use is of limited potential.

Adult↗
PubMed2000

[Direct ethanol metabolite ethyl glucuronide. Its value as alcohol intake and recurrence marker, methods of detection and prospects].

In clinical as well as in forensic practice biological state markers of high sensitivity and specificity capable of monitoring alcohol consumption of those in treatment for alcohol dependence or poly-drug abusers are required. The known markers cannot be considered satisfactory in respect of these parameters. Furthermore, they do not cover the entire time axis for alcohol consumption. These traditional markers are often influenced besides by alcohol, by age, gender and various of substances and non-alcohol-associated diseases. Ethyl glucuronide (EtG) is a non volatile, water soluble, stable upon storage, direct metabolite of ethanol with a molecular weight of 222 g/mol that was determined by our group in more than 1200 samples of body fluids, tissues and hair from over 200 patients, almost 200 drivers and postmortem with different GC/MS and ESI-LC/MS-MS methods using deuterium-labelled EtG as internal standard. With its specific time frame of detection intermediate between short-term and long-term markers and a particularly high sensitivity and specificity, ethyl glucuronide is a promising marker of alcohol consumption in general that can be detected for an extended time period after the complete elimination of alcohol from the body (up tp 80 h) and a marker for relapse control enabling the therapist to intervene at an early stage of relapsing behaviour. The complementary use of EtG together with other upcoming markers of alcohol consumption like phosphatidyl ethanol should lead to an improvement in treatment outcome, quality of life and cost reduction.

Alcohol Drinking↗
PubMed1999

Development of a sensitive E-screen assay for quantitative analysis of estrogenic activity in municipal sewage plant effluents.

A simplified proliferation test with human estrogen receptor-positive MCF-7 breast cancer cells (E-screen assay) was optimized and validated for the sensitive quantitative determination of total estrogenic activity in effluent samples from municipal sewage plants. After solid phase extraction of 1 l sewage on either 0.2 g polystyrene copolymer (ENV+) or 1 g RP-C18 material and removal of the solvent, analysis of the extracts in the E-screen assay could be performed without any clean-up step. This was even possible with untreated sewage. Parallel extraction of four sewage samples on both different solid phase materials gave comparable quantitative results in the E-screen. A blank sample did not induce cell proliferation. As additive behaviour of the estrogenic response of single compounds was proven for two different mixtures each containing three xenoestrogens, total estrogenic activity in the sewage samples, expressed as 17 beta-estradiol equivalent concentration (EEQ), could be calculated comparing the EC50 values of the samples with those of the positive control 17 beta-estradiol. The detection limit of the E-screen method was 0.05 pmol EEQ/l (0.014 ng EEQ/l), the limit of quantification 0.25-0.5 pmol EEQ/l (0.07-0.14 ng EEQ/l). In total, extracts of nine effluent and one influent sample from five different municipal sewage plants in South Germany were analyzed in the E-screen. All samples strongly induced cell proliferation in a dose-dependent manner which was completely inhibited by coincubation with 5 nM of the estrogen receptor-antagonist ICI 182,780. The proliferative effect relative to the positive control 17 beta-estradiol (RPE) was between 30 and 101%. 17 beta-Estradiol equivalent concentrations were between 2.5 and 25 ng/l indicating a significant input of estrogenic substances via sewage treatment plants into rivers.

Biological Assay↗
PubMed1999

[Cecum reservoir].

UNLABELLED: The choice of the best reconstruction technique following resection of either the stomach or the rectum remains a matter of discussion. While there is no problem in reconnecting intestinal segments, which do not serve as a reservoir, there are many different operation techniques to replace the stomach and rectum, producing significantly different functional results. The ileocecal segment offers an excellent intestinal reservoir combined with an antireflux mechanism, thus presenting an ideal replacement for the stomach. For replacement of the rectal reservoir as well, the ileocecal segment may be used in the first line of treatment. METHOD: The ileocecal segment was used in 20 patients following gastric resection and lymphadenectomy to reconstruct the intestinal passage between the esophagus and the duodenal stump (group A). In some further 44 patients (group B) the ileocecal segment was used to replace the rectum between the descending colon and the dentate line following resection for very low-grade rectal cancer. Mortality and morbidity were investigated in both groups. In group A quality of life, weight loss, dumping and reflux symptoms were evaluated. In group B continence, discrimination, defecation quality, urge and the patient satisfaction were investigated. All data were recorded prospectively. RESULTS: Early and late mortality were not different compared to other reconstruction types. In each group one patient died within 60 days postoperatively due to myocardial infarction. The morbidity following stomach replacement was 20%, following rectal replacement 4.6% during hospitalization and 13.8% during follow-up, respectively. One patient complained about heartburn, but endoscopically no pathology was detected in any patient. Three months postoperatively the patients' weight remained stable or started to increase. Three months following rectal replacement 87% of the patients were continent with further improvement over 2 years. Soiling mainly during the night remained over 2 years in 44%. 88% of the patients were completely satisfied 2 years postoperatively. CONCLUSION: The replacement of either the stomach or the rectum using the ileocecal segment with an adequate surgical technique is safe and produces excellent functional outcome regarding the reconstruction of the intestinal passage as well as the reservoir function of the primary organ. Furthermore, preservation of the duodenal passage after gastrectomy may prevent dysregulation of the endocrine and exocrine pancreatic hormones.

Anastomosis, Surgical↗
PubMed1999

The FLF MADS box gene: a repressor of flowering in Arabidopsis regulated by vernalization and methylation.

A MADS box gene, FLF (for FLOWERING LOCUS F ), isolated from a late-flowering, T-DNA-tagged Arabidopsis mutant, is a semidominant gene encoding a repressor of flowering. The FLF gene appears to integrate the vernalization-dependent and autonomous flowering pathways because its expression is regulated by genes in both pathways. The level of FLF mRNA is downregulated by vernalization and by a decrease in genomic DNA methylation, which is consistent with our previous suggestion that vernalization acts to induce flowering through changes in gene activity that are mediated through a reduction in DNA methylation. The flf-1 mutant requires a greater than normal amount of an exogenous gibberellin (GA3) to decrease flowering time compared with the wild type or with vernalization-responsive late-flowering mutants, suggesting that the FLF gene product may block the promotion of flowering by GAs. FLF maps to a region on chromosome 5 near the FLOWERING LOCUS C gene, which is a semidominant repressor of flowering in late-flowering ecotypes of Arabidopsis.

Arabidopsis↗
PubMed1999

Association between nonreentrant supraventricular tachycardia and atrioventricular node reentrant tachycardia: a presentation of dual AV node physiology.

Persistent simultaneous conduction of P waves over a fast and a slow nodal pathway defines the nonreentrant type of supraventricular tachycardia, usually not associated with reciprocating movements. We report a unique association between this uncommon tachycardia and a usual AV nodal reentrant tachycardia, made possible by the existence of three different nodal pathways.

Atrioventricular Node↗
PubMed1999

[Severe flecainide acetate poisoning. Apropos of a case].

Poisoning with flecainide acetate is rare and associated with a high mortality. This usually occurs after massive ingestion but can also be observed during therapeutic overdose in patients with renal failure or with amiodarone therapy. The prognostic depends on the haemodynamic and rhythmic effects of the overdose one sign of which is widening of the QRS complexes. Major sodium bicarbonate or lactate infusion is the generally prescribed treatment. The authors report one case of a patient with renal failure on amiodarone who survived a severe flecainide acetate overdose.

Aged↗
PubMed1999

Improvement-focused information technology for the clinical office practice: a patient registry for disease management.

A patient registry for disease management identifies and tracks key information concerning identified patients enrolled in a care management program. The software tool makes the proactive tracking and outreach of population-based management feasible. It is highly focused on the limited patient demographic and clinical information needed for this purpose. Automated medical records are beyond the reach of most physician practices, and many of those in use lack the features necessary for population-based management. We believe the patient registry will meet both the needs for disease-management focused support and the budget of the typical physician practice.

Chronic Disease↗
PubMed1998

Structural optimization affording 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-oxo-1,2,4-triazol-5-yl)methylmorpholine, a potent, orally active, long-acting morpholine acetal human NK-1 receptor antagonist.

Structural modifications requiring novel synthetic chemistry were made to the morpholine acetal human neurokinin-1 (hNK-1) receptor antagonist 4, and this resulted in the discovery of 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-ox o-1 ,2,4-triazol-5-yl)methyl morpholine (17). This modified compound is a potent, long-acting hNK-1 receptor antagonist as evidenced by its ability to displace [125I]Substance P from hNK-1 receptors stably expressed in CHO cells (IC50 = 0.09 +/- 0.06 nM) and by the measurement of the rates of association (k1 = 2.8 +/- 1.1 x 10(8) M-1 min-1) and dissociation (k-1 = 0.0054 +/- 0.003 min-1) of 17 from hNK-1 expressed in Sf9 membranes which yields Kd = 19 +/- 12 pM and a t1/2 for receptor occupancy equal to 154 +/- 75 min. Inflammation in the guinea pig induced by a resiniferatoxin challenge (with NK-1 receptor activation mediating the subsequent increase in vascular permeability) is inhibited in a dose-dependent manner by the oral preadmininstration of 17 (IC50 (1 h) = 0.008 mg/kg; IC90 (24 h) = 1.8 mg/kg), indicating that this compound has good oral bioavailbility and peripheral duration of action. Central hNK-1 receptor stimulation is also inhibited by the systemic preadministration of 17 as shown by its ability to block an NK-1 agonist-induced foot tapping response in gerbils (IC50 (4 h) = 0.04 +/- 0.006 mg/kg; IC50 (24 h) = 0.33 +/- 0.017 mg/kg) and by its antiemetic actions in the ferret against cisplatin challenge. The activity of 17 at extended time points in these preclinical animal models sets it apart from earlier morpholine antagonists (such as 4), and the piperidine antagonists 2 and 3 and could prove to be an advantage in the treatment of chronic disorders related to the actions of Substance P. In part on the basis of these data, 17 has been identified as a potential clinical candidate for the treatment of peripheral pain, migraine, chemotherapy-induced emesis, and various psychiatric disorders.

Acetals↗
PubMed1998

Amperometric phenol biosensor based on a thermostable phenol hydroxylase.

Phenol hydroxylase (EC 1.14.13.7) was produced using Bacillus stearothermophilus in a 5-1 batch fermentation leading to approximately 17 units after 6 h. The partially purified phenol hydroxylase was entrapped in a sol-gel matrix. The enzyme-loaded silica gel was attached to the sensitive top of a Clark-type oxygen electrode and its application as a phenol biosensor was tested. There was linearity between the maximal rate of oxygen consumption and phenol concentration in the range between 2.5 and 400 microM at 40 degrees C and pH 7.6. The signal could be read off after 10 s at a concentration of 400 microM phenol. The sensor lost 20% of its activity within 7 days. Para-substituted phenols were not detectable.

Biosensing Techniques↗
PubMed1998

Determination of BOD-values of starch-containing waste water by a BOD-biosensor.

The control of waste water plants is difficult or even impossible using the classical determination method for biological oxygen demand (BOD), because of its high time consumption of five days. A determination within some minutes is possible by microbial BOD-sensors. However, high molecular weight substances cannot be detected, a problem which can be overcome by the use of additional enzymes. For the application in a flow-through system to analyse starch containing waste water, alpha-amylase and amyloglucosidase were immobilized by adsorption to polystyrene or polypropylene carriers followed by crosslinking. Furthermore, covalent coupling to different nylon carriers, derivatives of chitin, silanized glass beads and silanized beads of foamed glass was tried. Chitin and Lewatit were the best suited carriers for the immobilization of alpha-amylase and amyloglucosidase. Two glass columns were filled with the immobilized enzymes and inserted into a commercial BOD-sensor containing the yeast Trichosporon cutaneum as biological component. The system was stable for more than two months under storage and one month under working conditions. A comparison of different starch types resulted in a hydrolysis of more than 80% in case of potato starch whereas grain starch was hydrolized only for 40-50%. Sensor-determined BOD-values of waste water with potato starch were nearly identical with BOD5-values resulting from the classical method.

Biosensing Techniques↗
PubMed1998

[Mesh-plug operation: a simple, rapid and complication-free technique for managing inguinal hernia].

INTRODUCTION: The optimal inguinal hernia repair technique is a matter of debate. The Shouldice operation has long been regarded as the gold standard. While specialized hernia clinics have reproduced good results, a recurrence rate for trainees and non-specialized surgeons of between 10% and 15% seems to be more common. Laparoscopic hernia surgery has brought decreasing postoperative morbidity, low post-operative disability and early return to work. These advantages of a tension-free technique are due to the use of a prosthetic mesh. It is largely the efforts of Gilbert, Lichtenstein and Rutkow/Robbins which have popularized the use of prosthetic mesh by an open anterior approach in the USA. METHODS: Since January 1997 we have prospectively evaluated the open mesh plug repair described by Rutkow/Robbins in Basel and Lugano. We have operated on 110 patients (103 male, 7 female). All patients were interviewed 4 weeks postoperatively at our clinic. RESULTS: There were no major complications. Two patients underwent reoperation for drainage of a haematoma. There was no early recurrence or infection. After 4 weeks 82% of all patients were back to normal activity. An early return to work has been noted (10 days on average for sedentary workers). CONCLUSION: The main advantages of this technique are simplicity, low cost, reduced post-operative disability and early return to work. It is much too early to say anything concerning recurrence in this series.

Adult↗
PubMed1998

Atrial vulnerability in patients with paroxysmal "lone" atrial fibrillation.

Little is known about the electrophysiological properties of the atrium predisposing to paroxysmal atrial fibrillation (AF), especially in patients without structural heart disease. This study was conducted to analyze intraatrial conduction, atrial refractoriness, and arrhythmia inducibility in patients with lone paroxysmal AF. An electrophysiological study was performed in 24 patients with a documented history of lone paroxysmal AF but in sinus rhythm at the time of the electrophysiological study. Twelve patients without any history of atrial arrhythmias served as controls. The patients with lone paroxysmal AF showed a significant prolonged local conduction time S1A1 (70 +/- 21 ms vs 36 +/- 12 ms, P < 0.0001), a lack of rate adaptation of the functional refractory period (FRP changes/cycle length changes < 10% in 15 of 24 patients with lone paroxysmal AF vs 1/12 controls, P = 0.002) and a higher incidence of inducible AF with only one extrastimulus (13/24 vs 0/12, P = 0.0014). The total P wave duration in the surface ECG (89 +/- 14 ms vs 83 +/- 8 ms, P = 0.15), the intraatrial conduction time (36 +/- 14 ms vs 28 +/- 8 ms, P = 0.07), the presence of a fragmented atrial electrogram (16/24 vs 7/12, P = 0.62), the absolute value of the effective refractory period (204 +/- 28 ms vs 212 +/- 23 ms, P = 0.42), and the vulnerability index (3.0 +/- 1.5 vs 3.6 +/- 1.5, P = 0.26) were not statistically different between the two groups. The presence of a prolonged (> 50 ms) S1A1 and/or the presence of a lack of rate adaptation of the FRP and/or the presence of inducible AF identified patients with spontaneous lone paroxysmal AF with a sensitivity of 96%, a specificity of 67%, a positive predictive value of 85%, and a negative predictive value of 89%. In patients with lone paroxysmal AF, the electrophysiological study using conventional techniques allows not only to detect AF inducibility using a nonaggressive protocol, but also to reveal several electrophysiological abnormalities related to the atrial substrate itself. This atrial vulnerability may explain the high incidence of recurrences in patients with lone paroxysmal AF.

Atrial Fibrillation↗
PubMed1998

Isolation, characterization, and heterologous expression of the novel lantibiotic epicidin 280 and analysis of its biosynthetic gene cluster.

Epicidin 280 is a novel type A lantibiotic produced by Staphylococcus epidermidis BN 280. During C18 reverse-phase high-performance liquid chromatography two epicidin 280 peaks were obtained; the two compounds had molecular masses of 3,133 +/- 1.5 and 3,136 +/- 1.5 Da, comparable antibiotic activities, and identical amino acid compositions. Amino acid sequence analysis revealed that epicidin 280 exhibits 75% similarity to Pep5. The strains that produce epicidin 280 and Pep5 exhibit cross-immunity, indicating that the immunity peptides cross-function in antagonization of both lantibiotics. The complete epicidin 280 gene cluster was cloned and was found to comprise at least five open reading frames (eciI, eciA, eciP, eciB, and eciC, in that order). The proteins encoded by these open reading frames exhibit significant sequence similarity to the biosynthetic proteins of the Pep5 operon of Staphylococcus epidermidis 5. A gene for an ABC transporter, which is present in the Pep5 gene cluster but is necessary only for high yields (G. Bierbaum, M. Reis, C. Szekat, and H.-G. Sahl, Appl. Environ. Microbiol. 60:4332-4338, 1994), was not detected. Instead, upstream of the immunity gene eciI we found an open reading frame, eciO, which could code for a novel lantibiotic modification enzyme involved in reduction of an N-terminally located oxopropionyl residue. Epicidin 280 produced by the heterologous host Staphylococcus carnosus TM 300 after introduction of eciIAPBC (i.e., no eciO was present) behaved homogeneously during reverse-phase chromatography.

Amino Acid Sequence↗