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Biomedical subjects

E Lenz

Publications and source records attributed to E Lenz.

At least 19 recordsLinked to original sources

Spectroscopic characterisation and identification of ecdysteroids using high-performance liquid chromatography combined with on-line UV--diode array, FT-infrared and 1H-nuclear magnetic resonance spectroscopy and time of flight mass spectrometry.

A prototype multiply hyphenated reversed-phase HPLC system has been applied to the analysis of a mixture of pure ecdysteroids and an ecdysteroid-containing plant extract. Characterisation was achieved via a combination of diode array UV, 1H NMR, FT-IR spectroscopy and time of flight (TOF) mass spectrometry. This combination of spectrometers allowed the collection of UV, 1H NMR, IR and mass spectra for a mixture of pure standards enabling almost complete structural characterisation to be performed. The technique was then applied to a partially purified plant extract in which 20-hydroxyecdysone and polypodine B were identified despite incomplete chromatographic resolution and the presence of co-chromatographing interferents. The experimental difficulties in the use of such a systems for these analytes are described.

Chromatography, High Pressure Liquid↗

Anxiety and depression: incidence and patterns in patients after coronary artery bypass graft surgery.

The purpose of this longitudinal study was to describe the incidence and patterns of anxiety and depression in older patients who undergo coronary bypass graft surgery and to determine the influence of gender and age on psychological recovery. A sample of 31 patients was assessed pre- and postoperatively at 2 to 3 days and at 2, 4, 8, and 12 weeks. Younger subjects experienced higher anxiety, reaching statistical significance at 2 and 4 weeks. Women had significantly higher trait and state anxiety and a higher, nonsignificant incidence of depression at all times. Younger subjects were more depressed at 2 to 3 days and at weeks 2 and 4. Because women and younger patients are at higher risk for psychological distress, they should be targeted for interventions.

Age Distribution↗

An NMR-based metabonomic approach to investigate the biochemical consequences of genetic strain differences: application to the C57BL10J and Alpk:ApfCD mouse.

As the human genome sequencing projects near completion, there is an active search for technologies that can provide insights into the genetic basis for physiological variation and interpreting gene expression in terms of phenotype at the whole organism level in order to understand the pathophysiology of disease. We present a novel metabonomic approach to the investigation of genetic influences on metabolic balance and metabolite excretion patterns in two phenotypically normal mouse models (C57BL10J and Alpk:ApfCD). Chemometric techniques were applied to optimise recovery of biochemical information from complex (1)H NMR urine spectra and to determine metabolic biomarker differences between the two strains. Differences were observed in tricarboxylic acid cycle intermediates and methylamine pathway activity. We suggest here a new 'metabotype' concept, which will be of value in relating quantitative physiological and biochemical data to both phenotypic and genetic variation in animals and man.

Amino Acids↗

Reversed-phase high-performance liquid chromatography combined with on-line UV diode array, FT infrared, and 1H nuclear magnetic resonance spectroscopy and time-of-flight mass spectrometry: application to a mixture of nonsteroidal antiinflammatory drugs.

A prototype multiply hyphenated system has been applied to the analysis of a mixture of nonsteroidal antiinflammatory drugs separated by reversed-phase HPLC. Characterization of the model NSAIDs was achieved via a combination of diode array UV, 1H NMR, FT-IR spectroscopy, and time-of-flight mass spectrometry. This combination of spectrometers allowed the collection of UV, 1H NMR, IR, and mass spectra together with atomic composition data enabling almost complete structural characterization to be performed.

Anti-Inflammatory Agents, Non-Steroidal↗

Flow injection spectroscopic analysis of model drugs using on-line UV-diode array, FT-infrared and 1H-nuclear magnetic resonance spectroscopy and time-of-flight mass spectrometry.

A prototype flow injection analysis (FIA) system for the characterisation of compounds via a combination of diode array UV, 1H NMR, FT-IR spectroscopy and time-of-flight (TOF) mass spectrometry has been investigated using a number of pharmaceuticals and related compounds as model compounds. This combination of spectrometers allowed the on-flow collection of UV, 1H NMR, IR and mass spectra together with atomic composition data, enabling almost complete structural characterisation to be performed. Practical detection limits with the current system were in the region of 50 micrograms, however, the use of state of the art spectrometers would result in a significant reduction in the amount of material required.

Flow Injection Analysis↗

Investigation of the metabolism of 14C/13C-practolol in rat using directly coupled radio-HPLC-NMR-MS.

1. The metabolic fate of 14C/13C-practolol was investigated using on-line HPLC-NMR-MS following oral administration to rat. The major route of elimination for the radiolabel was via the urine with the principal biotransformation products confirmed as the 2-hydroxy- and 2-hydroxyglucronide metabolites. 2. In addition, futile deacetylation, determined by the replacement of 13C-labelled acetyl groups with endogenous 12C-acetyls accounted for approximately 7-10% of the urinary metabolites, corresponding to approximately 5% of the dose undergoing N-deacetylation. 3. Evidence for chiral metabolism was sought via NMR of isolated metabolites using beta-cyclodextrin as a chiral shift agent. Practolol was excreted as a racemate. However, some enantioselective metabolism/excretion had occurred as the hydroxy- and hydroxyglucuronide were not excreted as racemic mixtures. 4. Directly coupled radio-HPLC-NMR-MS is extremely effective for the identification of the metabolites of radiolabelled xenobiotics in urine samples.

Adrenergic beta-Antagonists↗

Long-term experience with laparoscopic retroperitoneal lymph node dissection in the management of low-stage testis cancer.

OBJECTIVES: We describe our experience with laparoscopic retroperitoneal lymphadenectomy (LRLA) in 34 patients with low-stage germ cell tumors treated from 1992 to 1998. All patients had clinical stage-I disease with no clinical evidence (CT scan, ultrasound, tumor markers) of metastases. A laparoscopic dissection was used to assess the pathologic status of the relevant retroperitoneal lymph nodes. MATERIAL AND METHODS: 17 patients were treated by a transperitoneal laparoscopic approach, whereas in the last 17 patients retroperitoneoscopic retroperitoneal lymph node dissection was performed. The lymph node dissection was performed identically to open surgery with the modified template according to Weissbach including the paracaval, interaortocaval, upper pre-aortic, and right common iliac zonal nodes for right-sided tumors, and para-aortic, upper pre-aortic zones for left-sided tumors. Retrieval of the lymph node chains was accomplished using a small organ bag. RESULTS: The procedure could be completed successfully in 30 of 34 patients with stage-I disease. In these cases the mean duration of the procedure was 248 min. In 3 patients the lymphadenectomy was abandoned, because frozen section showed metastasis. In 1 case conversion to open surgery was necessary because of bleeding from the aorta. One patient developed a delayed ureteral stenosis which required operative repair. Three patients required temporary insertion of an indwelling ureteral stent, and another patient had a pulmonary embolism with an uneventful outcome. One patient with a LRLA on the right side later developed retrograde ejaculation. In 6 of the 33 patients (18%) embryonal carcinoma or mixed carcinoma was found. The postoperative hospital stay averaged 5.3 (3-9) days for the patients without complications or conversion to open surgery. After a median follow-up of 40 months no regional relapse occurred, but 2 patients developed pulmonary metastases which were treated successfully by three cycles of platinum-based chemotherapy. All patients have no evidence of disease. CONCLUSIONS: Our experience suggests that LRLA is a safe and accurate method for low-stage germ cell tumors with minimal invasiveness, but because of its technical difficulty it should be restricted to experienced centers.

Follow-Up Studies↗

Congenital deficiency of vitamin K dependent coagulation factors in two families presents as a genetic defect of the vitamin K-epoxide-reductase-complex.

Hereditary combined deficiency of the vitamin K dependent coagulation factors is a rare bleeding disorder. To date, only eleven families have been reported in the literature. The phenotype varies considerably with respect to bleeding tendency, response to vitamin K substitution and the presence of skeletal abnormalities, suggesting genetic heterogeneity. In only two of the reported families the cause of the disease has been elucidated as either a defect in the gamma-carboxylase enzyme (1) or in a protein of the vitamin K 2,3-epoxide reductase (VKOR) complex (2). Here we present a detailed phenotypic description of two new families with an autosomal recessive deficiency of all vitamin K dependent coagulation factors. In both families offspring had experienced severe or even fatal perinatal intracerebral haemorrhage. The affected children exhibit a mild deficiency of the vitamin K dependent coagulation factors that could be completely corrected by oral substitution of vitamin K. Sequencing and haplotype analysis excluded a defect within the gamma-carboxylase gene. The finding of highly increased amounts of vitamin K epoxide in all affected members of both families indicated a defect in a protein of the VKOR-multienzyme-complex. Further genetic analysis of such families will provide the basis for a more detailed understanding of the structure-function relation of the enzymes involved in vitamin K metabolism.

Blood Coagulation Factors↗

Postdischarge medication use of elderly cardiac patients from urban and rural locations.

BACKGROUND: After discharge from an acute care setting, elderly cardiac patients take a variety of medications in the home setting. Their pharmacologic regimens are often quite complex, and may involve drugs from several therapeutic categories. Patterns of medication use can be one measure of patient status after discharge because they can indicate whether medical conditions are stabilized. A problem related to medications during the postdischarge period is residence of the patient. For persons discharged to rural settings, access to health care resources and follow-up monitoring of medications may be problematic. METHODS: This longitudinal study followed postdischarge medication use over a 5-month period. Thirty-two elderly persons admitted to a large tertiary care center for treatment of cardiac conditions were recruited. Baseline information was collected on demographics and health status, and subjects were then interviewed by telephone at 2, 4, 12, and 20 weeks postdischarge. Analysis of functional health complaints assessed by the Medical Outcomes Short Form (SF-36) and cardiac symptom scores were correlated with new and standing prescriptions over time and across geographic locations. Potential confounders such as age, gender, and severity of illness were controlled for. RESULTS: Statistical analyses on continuity of medication use and changes in the category of medication prescribed revealed that urban subjects were prescribed more drugs and experienced significantly more alterations in their drug regimens. CONCLUSIONS: Contrary to expectations, urban subjects appeared to do worse over the postdischarge period with greater drug utilization that directly predicted the number of hospital readmissions and number of emergency room visits, even though their severity of illness was no different from their rural counterparts at the time of discharge.

Aged↗

A compendium of potential energy maps of zeolites and molecular sieves.

We present potential maps of xenon in 20 different zeolites and molecular sieves. The potential maps reveal both the accessible pore volume and localized adsorption sites and so are important in understanding adsorption and diffusion processes in nanoporous materials. We examine zeolites and molecular sieves with one-dimensional channel-like nanopores (zeolite-Theta 1, AlPO4-5, zeolite-Omega, zeolite-L, ZSM-12, AlPO4-8, and VPI-5), with two-dimensional intersecting channel-like nanopores (ZSM-5 [silicalite], ZSM-11, ferrierite, mordenite, and zeolite-Beta), and with three-dimensionally connected cagelike nanopores (zeolite-A, zeolite-Rho, zeolite-Y, sodalite, chabazite, cloverite, cation-poor zeolite-A, and cation-rich zeolite-A). We report the fraction of pore volume accessible, the maximum energy well depth at the adsorption sites, and the activation energy to move between sites. We note several examples of surprising similarities and differences between various molecular sieves. In several instances, we show that these potential profiles are relevant for other small Lennard-Jones-like molecules. By comparison with published Monte Carlo and molecular dynamics simulations, we show that the density distributions of adsorbates at low density are well predicted by the potential maps.

Cations↗

Factor VIII inhibitors in patients with hemophilia A: epidemiology of inhibitor development and induction of immune tolerance for factor VIII.

Factor (F) VIII inhibitor development remains one of the most serious complications in the treatment of hemophilia A. Former and recent studies on inhibitor development revealed that patients with severe hemophilia A and positive inhibitor family history are at highest risk of developing an inhibitor. Comparison of recent inhibitor incidence studies on previously untreated patients indicate that the risk of inhibitor development under treatment with recombinant FVIII concentrates is comparable to the inhibitor incidence under FVIII substitution by plasma-derived concentrates. However, longer observation periods are necessary to draw final conclusions. Since inhibitor development may result in inefficacy of FVIII concentrates in the treatment of severe bleedings, the induction of immune tolerance (IT) is still of main concern. Various regimens to induce IT by application of FVIII concentrates have been conducted up to now. Success rate appears to be influenced by low to high responder status, number of exposure days before onset of treatment, and dosage of therapeutic regimen. Especially, discontinuation of IT therapy seems to be associated with failure of therapy. Taking into account available data on IT therapy, we recommend early onset of a high dosage regimen in high responder patients as soon as possible after inhibitor detection, as this is associated with higher success rate and shorter elimination time.

Adolescent↗

Coupling of HPLC with 19F- and 1H-NMR spectroscopy to investigate the human urinary excretion of flurbiprofen metabolites.

Results of an on-line HPLC-NMR analysis of human urine from a volunteer administered the anti-inflammatory drug flurbiprofen are reported. The two major human urinary metabolites, namely the glucuronides of flurbiprofen and of 4'-hydroxyflurbiprofen, have been identified using 1H- and 19F-NMR spectroscopy. In vivo conjugation of the racemic drug and its metabolites with D-glucuronic acid results in diastereomeric molecules which give resolved NMR spectra thereby permitting the diastereomeric proportions to be evaluated. The cause of the observed deviation from equal proportions is discussed. This study represents the first use of both 19F- and 600 MHz 1H-NMR spectroscopy coupled to HPLC.

Chromatography, High Pressure Liquid↗

[Radioactivity of bone cement].

A total of 14 samples of different types of bone cement from five different manufacturers were examined for their radioactivity. Each of the investigated bone cements showed a low radioactivity level, i.e. between < 1 and 100 Bq/kg. The content of U-238 and K-40 always was below the limit of detection (< 1-< 10 Bq/kg). Significant differences were detected in the amount of Ra-226, Pb-210, and Ra-228 detected between different samples of the same product from the same manufacturer, as well as between various types of cements. The highest radioactivity level was measured for Ra-226. Although stochastic radiation effects can not totally be excluded, it is extremely unlikely that the small amount of radioactive substances additionally transferred into the body by the bone cement has negative effects on the recipient's organism or on the fate of the alloplastic implant: "The risk factor and extrapolation in a low dosage range ... do not lead to an underestimation but more likely to an overestimation of the radiation hazard" [18].

Bone Cements↗

Suppression of transformed phenotype in hybrids of v-fgr and v-raf transformed rat-1 cells with rat embryonic fibroblasts is due to transcriptional inactivation of viral oncogenes.

Rat-1 cells that had been transformed to tumorigenicity by transfection with the retroviral oncogenes v-raf from 3611-murine sarcoma virus, or v-fgr from Gardner-Rasheed feline sarcoma virus were fused with rat embryonic fibroblasts at an early passage. In both fusion experiments hybrid cells were isolated that exhibited normal morphology, anchorage requirement for proliferation, and either no tumorigenicity (v-fgr) or extended latency periods for tumor growth (v-raf) in nude mice. Transcription of viral oncogenes is drastically reduced in hybrid cells (at least 30-fold compared to their transformed parental cells), while the half-life of the corresponding transcripts is not effected. In the chromatin of hybrid cells the integrated retroviral oncogenes are as sensitive to degradation with pancreatic DNase I as the endogenous actin gene. Thus the observed down regulation of proviral transcript levels does not correlate with changes in chromatin structure. We conclude that in hybrids of (v-fgr)- and (v-raf)-transformed Rat-1 cells with embryonic fibroblasts, transcription of the retroviral oncogenes appears to be repressed by trans-acting factors of the normal parental cell.

Animals↗

[Rare site of malignant melanoma].

Primary melanoma of the vagina is a rare tumor associated with a poor prognosis. We report on a 82 years old woman with a malignant melanoma of the vagina. The treatment performed was the removal of the vaginal tumor and a hemivulvectomy followed by a chemotherapy over 6 month. A recurrence of the tumor and the development of metastases in the brain and in the lungs was observed 3 weeks after the end of the chemotherapy. The patient expired 10 month after the primary treatment.

Aged↗