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Biomedical subjects

M Lanz

Publications and source records attributed to M Lanz.

At least 19 recordsLinked to original sources

Comparative evaluation of the powder properties and compression behaviour of a new cellulose-based direct compression excipient and Avicel PH-102.

This study compares the compression behaviour of a new cellulose-based tableting excipient, hereinafter referred to as UICEL-A/102, and Avicel PH-102, a commercial direct compression excipient commonly referred to as microcrystalline cellulose (MCC). UICEL-A/102 shows the cellulose II lattice, while Avicel PH-102 belongs to the cellulose I polymorphic form. The median particle diameters of UICEL-A/102 and Avicel PH-102 fractions used in the study were 107 and 97 microm, respectively. Compared with Avicel PH-102, UICEL-A/102 was more dense; the relative poured and tapped densities were: 0.277 and 0.327 (vs 0.195 and 0.248 for Avicel PH-102), respectively. The true density, rhotrue, of the two materials was comparable ( approximately 1.56 g cm(-3)). The slopes of the in-die and out-of-die Heckel curves for Avicel PH-102 were steeper than for UICEL-A/102. The relative density versus applied pressure plot was in good agreement with the modified Heckel equation. The out-of-die and in-die minimal pressure susceptibility (chipmin) values calculated were 3.36 x 10(-3) and 8.09 x 10(-3) MPa(-1) for UICEL-A/102 and 8.00 x 10(-3) and 16.12 x 10(-3) MPa(-1) for Avicel PH-102, respectively. The elastic recovery profiles showed UICEL-A/102 to be more elastic than Avicel PH-102. In conclusion, UICEL-A/102 and Avicel PH-102 differ in their compression behaviour under pressure. The different polymorphic forms could provide a possible explanation.

Cellulose↗

Neuropsychiatric thalamocortical dysrhythmia: surgical implications.

Clearly, more clinical experience must be amassed to define in detail the possibilities of this surgical approach in disabling neuropsychiatric disorders. We propose, however, that the evidence for benign and efficient surgical intervention against the neuropsychiatric TCD syndrome is already compelling. The potential appearance of strong postoperative reactive manifestations requires a close association between surgery and psychotherapy, with the latter providing support for the integration of the new situation as well as the resolution of old unresolved issues.

Adult↗

SCA17 caused by homozygous repeat expansion in TBP due to partial isodisomy 6.

An expanded polyglutamine domain in the TATA-binding protein (TBP) has been described in patients with spinocerebellar ataxia type 17 (SCA17) characterized by cerebellar ataxia associated with dementia. TBP is a general transcription initiation factor that regulates the expression of most eukaryotic genes transcribed by RNA polymerase II. SCA17, as an autosomal dominantly inherited progressive neurodegenerative disorder, is caused by heterozygous expansion of a CAG repeat coding for glutamine. Alleles with 27 to a maximum of 44 glutamine residues were found as the normal range, whereas expansions above 45 repeat units were considered pathological. Here, we present a patient with a very severe phenotype with a late onset but rapidly progressing ataxia associated with dementia and homozygous 47 glutamine residues caused by an apparent partial isodisomy 6. This extraordinary case has important implications for the insights of TBP and SCA17. The expanded polyglutamine domain in both TBP copies is not correlated with embryonic death indicating that the normal function of the protein is not disrupted by this kind of mutation but may account for the dementia seen in this patient.

Adult↗

Aminoborohydrides. 11. Facile reduction of N-alkyl lactams to the corresponding amines using lithium aminoborohydrides.

[reaction: see text] Various five- and six-membered N-alkyl lactams were reduced to the corresponding cyclic amines using lithium N,N-dialkylaminoborohydrides (LAB). Most of the reductions were essentially complete after refluxing in THF for 2 h. The cyclic amine products were easily isolated after an aqueous workup in very good to excellent yields. It is possible to selectively reduce most functional groups, such as esters, in the presence of a lactam using LAB reagents.

Amines↗

Parent-child communication and adolescent self-esteem in separated, intercountry adoptive and intact non-adoptive families.

The purpose of the present study was to verify whether there are some differences in parent-child communication and in adolescent self-esteem among adoptive, separated and intact non-adoptive families and to investigate the extent to which parent-child communication is related to adolescent self-esteem in the three types of families. The study sample was composed of 450 adolescents aged between 11 and 17 years (160 from intact non-adoptive families, 140 from separated or divorced families and 150 from intercountry adoptive families). Subjects completed the Parent-Adolescent Communication Scale by Barnes and Olson, the Rosenberg Self-esteem Scale and some socio-demographic items. The results show that adolescents from separated families have more difficulties in their relationships with both the mother and the father than their peers, and that adoptive children perceive a more positive communication with their parents than biological children. Moreover, adoptees showed lower self-esteem than the other two groups of adolescents. Lastly, it emerged that male and female adolescents' self-esteem is related to positive communication with both parents in intact non-adoptive families, while no link was significant for male and female children of divorced parents or for adoptees.

Adolescent↗

Significant others: Italian adolescents' rankings compared with their parents.

In a study of social context in which adolescents live from an intergenerational perspective, the purpose was comparison of significant others of the generation of Italian adolescents (n = 595) and their parents' recalled others significant during adolescence (397 fathers and 416 mothers). Analysis showed the predominance of parents and above all the mother as the most significant others for both generations during adolescence. Further, today's adolescent generation attributed less importance to other unrelated adults than their parents recalled.

Adolescent↗

Capillary electrophoresis in clinical toxicology.

During the past decade, capillary electrophoresis (CE) emerged as a promising, effective and economic approach for separation of a large variety of substances, including those encountered in clinical toxicology. Reliable and automated CE instruments became commercially available and promoted the exploration of an increasing number of CE methods for illicit and licit drugs in body fluids. The widespread applicability of CE, its enormous separation power and high-sensitivity detection schemes make this technology an attractive and promising tool. This review provides an overview of the key achievements encountered with CE in clinical toxicology, including (i) the rapid assessment of drug intoxications via direct sample injection, (ii) the screening for and determination of illicit and licit drugs in body fluids with drug extraction, drug concentration (stacking) and chiral discrimination, (iii) the application of immunological single and multianalyte assays in the capillary format to the screening for drugs in body fluids, and (iv) drug confirmation by on-column multiwavelength absorbance and fluorescence detection and/or CE coupled to mass spectrometry. With its distinct features (automation, small sample size, minimal sample preparation, requirement of almost no organic solvents, ease of buffer change and method development, speed of analysis, low cost of capillaries and chemicals) CE has a bright future and the twenty-first century will witness the widespread use of a large number of simple and reliable CE based assays for drugs, methods that will be employed in clinical toxicology, therapeutic drug monitoring and forensic science.

Body Fluids↗

Screening for urinary methadone by capillary electrophoretic immunoassays and confirmation by capillary electrophoresis-mass spectrometry.

This paper characterizes competitive binding, electrokinetic capillary-based immunoassays for urinary methadone using reagents which were commercialized for a fluorescence polarization immunoassay. After incubation of 25 microL urine with the reactants, a small aliquot of the mixture is applied onto a fused-silica capillary and the unbound fluorescein-labeled methadone tracer is monitored by capillary electrophoresis with on-column laser-induced fluorescence detection. Configurations in presence and absence of micelles were investigated, found to be capable of recognizing urinary methadone concentrations > or = 10 ng/mL, and shown to be suitable for rapid methadone screening of patient urines. Based upon shorter run times and a much better separation of free tracer and antibody-tracer complex, conditions without micelles are preferred. For confirmation analysis of urinary methadone and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), capillary electrophoresis in a pH 4.6 ammonium acetate-acetic acid buffer was interphased to an atmospheric pressure ionization triple quadrupole mass spectrometry system. Using positive ion electrospray ionization and the tandem mass spectrometry mode with collision-induced dissociation in the collision cell, fragmentation of the two substances was determined. For confirmation via direct urine injection or application of a urinary extract, in-source fragmentation was employed and the first quadrupole was operated in the selected ion monitoring mode by switching between the masses of relevant precursor/product ion sets for methadone (m/z = 310, 265) and EDDP (m/z = 278, 249, 234). This capillary electrophoresis-mass spectrometry approach is shown to permit the confirmation of methadone and EDDP in patient urines that tested positive for methadone using electrokinetic capillary-based immunoassays, a fluorescence polarization immunoassay, and capillary electrophoresis with UV absorption detection.

Electrophoresis, Capillary↗

Enantiomeric separation of methadone by cyclodextrin-based capillary and recycling isotachophoresis.

The separation of methadone enantiomers by cationic capillary isotachophoresis (CITP) and recycling isotachophoresis (RITP) having (2-hydroxypropyl)-beta-cyclodextrin (OHP-beta-CD) as chiral selector in the leading electrolyte is described. Sodium acetate/acetic acid (pH between 4 and 5) served as leading electrolyte (catholyte) and acetic acid as terminator (anolyte). Complete separation of the enantiomers was obtained by CITP in a 50 microm internal diameter (ID) fused-silica capillary and in a 500 microm ID Teflon capillary. In the first approach, enantiomeric separation could be monitored via UV absorbance detection at low wavelength. With the second instrumental setup, an additional conductivity sensor permitted the visualization of the enantiomeric separation and the characterization of the buffer system employed. A 10 mM sodium acetate/acetic acid leading buffer of pH 4.3, containing 5 mM OHP-beta-CD, was found to provide best enantiomeric separation and was thus chosen for RITP. With RITP processing of a few mg of racemic methadone, partial separation of methadone enantiomers was obtained. R-(-)-methadone and S-(+)-methadone were found to be significantly (up to about 80%) enriched at the front and back side, respectively, of the isotachophoretic zone. The enantiomeric composition of methadone in the collected fractions was assessed by chiral capillary zone electrophoresis (CZE) and circular dichroism spectroscopy. CZE was found to represent a simple and efficient method for the determination of the enantiomeric excess, whereas the latter technology was noted to be the superior approach for properly characterizing fractions that contain similar amounts of the two enantiomers. Furthermore, chiral RITP and analysis of the collected fractions by circular dichroism spectroscopy is shown to be potentially useful for identification of single enantiomers in absence of pure chiral standards.

Circular Dichroism↗

Enantioselective determination of 3,4-methylene-dioxymethamphetamine and two of its metabolites in human urine by cyclodextrin-modified capillary zone electrophoresis.

Using capillary zone electrophoresis with a phosphate buffer at pH 2.5 containing 30 mM (2-hydroxypropyl)-beta-cyclodextrin as chiral selector, the simultaneous separation of the enantiomers of 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) and its two metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA) and 3,4-methylenedioxyamphetamine (MDA) in human urine is reported. The assay described is based upon enzymatic hydrolysis of conjugated HMMA (major urinary metabolite) and solid-phase extraction followed by injection of a few nL of the extract onto a 50 microm internal diameter (ID) fused-silica capillary of 60 cm length. Solutes are detected via on-column absorbance at 195 nm. For 375 ng/mL drug levels, intraday and interday imprecision is < 4%. With 5 mL urine samples, the detection limit is in the 20-50 ng/mL range. Via analysis of the urines of two patients, the metabolism of MDMA is demonstrated to be enantioselective, with significantly higher urinary amounts of R-(-)-MDMA being excreted compared to S-(+)-MDMA. Within 72h after drug administration one patient was determined to excrete 42.28 and 10.16% of the racemic MDMA dose (1.5 mg/kg body weight) as R-(-) and S-(+)-MDMA enantiomers, respectively. Corresponding values for the second subject were found to be 28.63 and 9.34%. The metabolism of the enantiomers of the two metabolites showed interindividual differences. The first and second detected HMMA enantiomers represented 3.79 and 5.42% (first subject) and 8.51 and 4.36% (second), respectively, of the administered MDMA dose. For the MDA enantiomers, corresponding values were 2.44, 1.76, 0.75, and 0.79%, respectively.

3,4-Methylenedioxyamphetamine↗

Characterization of stereoselectivity and genetic polymorphism of the debrisoquine hydroxylation in man via analysis of urinary debrisoquine and 4-hydroxydebrisoquine by capillary electrophoresis.

Using capillary zone electrophoresis with a phosphate buffer at pH 2.5 containing 50 mM heptakis-(2,3,6-tri-O-methyl)-beta-CD as chiral selector, the separation of the enantiomers of the main metabolite of debrisoquine (DEB), 4-hydroxydebrisoquine (4-OHDEB), is reported. For extraction of underivatized urinary DEB, S-4-OHDEB and R-4-OHDEB, a procedure using disposable cartridges containing a polystyrene-based polymer was developed. A few nL of the extracts were analyzed in a 60 cm fused-silica capillary of 50 microns ID and solute detection was effected at 195 nm. For all three compounds, a mean (n = 5) recovery of about 73% and a detection limit of about 150 ng/mL were noted. Data obtained with urines that were received for routine phenotyping with DEB and mephenytoin confirmed the almost exclusive formation of S-4-OHDEB. Under the described conditions, no R-4-OHDEB could be detected. With these data and those obtained employing no chiral selector in the buffer, differentiation between extensive metabolizer phenotypes (EM) and poor metabolizer phenotypes (PM) for DEB was unambiguously possible by the presence of a significant peak and no (or minor) peak for 4-OHDEB, respectively. Data obtained for ten EM subjects and five PM subjects were found to agree with those generated by the routine assay based on gas chromatography. The capillary electrophoretic assays described are simple, reproducible (relative standard deviation of peak area ratios < 3%), require no sample derivatization, consume no halogenated organic solvents, and operate with inexpensive separation columns as well as small amounts of chemicals.

Debrisoquin↗

Qualitative assessment of blood washing with the continuous autologous transfusion system (CATS)

A number of different blood-processing methods can be used at the end of cardiopulmonary bypass (CPB) to improve the quality of autologous blood. They include centrifugation, hemofiltration and cell-washing. They differ in processing time required, cost of disposables and the quality of the processed autologous blood product. The newly developed continuous auto-transfusion system (CATS: Fresenius AG, Bad Homburg) uses a continuous cell-washing method. In a prospective study, the oxygenator blood of 10 patients was processed at the end of cardiac surgery with CATS and the quality of autologous blood before and after processing was compared. The processing volumes and the time required were recorded. The concentrations and elimination rates of blood parameters and waste products such as activated coagulation and complement products were measured. At the end of CPB a mean volume of 1,010 +/- 174 ml diluted oxygenator blood was processed and concentrated to 310 +/- 88 ml in 11.0 +/- 2.2 mins. Cellular elements such as erythrocytes and leucocytes were mostly retained and their concentration showed a significant increase after processing (250% and 210% respectively; p < 0.01). Thus, the blood processing with CATS resulted in an excellent hemoconcentration (hematocrit 62 +/- 3 vs. 24 +/- 4% before processing) with a consistent reproducibility. On the other hand, the CATS concentrate showed a significant loss of autologous plasma proteins. Likewise, all water soluble elements such as waste products are significantly lower in concentration after processing and, if calculated by quantity, they show a high elimination rate (> 93%). In conclusion, the continuous autologous transfusion system permits an automated, rapid and continuous processing of autologous blood yielding a standardised high quality erythrocyte concentrate.

Aged↗

[Effect of postoperative retransfusion of autologous blood products on hemostasis in heart surgery].

In cardiac surgery a reduction of homologous blood products is mainly achieved by autologous blood salvage. Unprocessed retransfusion of autologous blood may induce changes in hemostasis. We assessed changes of activated clotting times (ACT) after retransfusion of unprocessed (1) oxygenator blood and (2) shed mediastinal blood. In 41 patients undergoing cardiac surgery (37 revascularization and 4 valve procedures) with a mean cardiopulmonary bypass time of 116.3 min, ACT was measured at the following time points: pre- and postoperatively, and before and after retransfusion of oxygenator blood and shed mediastinal blood. A significant prolongation of ACT values was only seen between pre- to postoperative blood (p < 0.003). Retransfusion of oxygenator blood changed ACT from 120 +/- 25 vs 116 +/- 17 sec and retransfusion of shed mediastinal blood showed a mean ACT of 118 +/- 14 vs 115 +/- 20 sec from before to after transfusion. There was a significant correlation between the ACT value in the unprocessed oxygenator blood and the ACT value measured in the patient after retransfusion (r = 0.41, p < 0.02). 6 patients receiving over 1 litre of unprocessed autologous blood (either from the oxygenator or the mediastinum) in less than 60 minutes showed a significant increase of ACT value after transfusion (p < 0.05). Hence, under normal conditions, retransfusion of unprocessed autologous blood will not significantly alter hemostasis measured by the ACT test in patients undergoing cardiac surgery.

Adult↗

Characterization of the stereoselective metabolism of methadone and its primary metabolite via cyclodextrin capillary electrophoretic determination of their urinary enantiomers.

Using capillary zone electrophoresis with a phosphate buffer at pH 3, containing 4.3 mM hydroxypropyl-beta-cyclodextrin as chiral selector, the simultaneous separation of the enantiomers of methadone and its primary metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), is reported. After solid-phase extraction and analysis of the reconstituted extracts in a 60 cm fused-silica capillary of 50 microns ID within about 25 min, the mean S/R enantiomeric ratio of methadone in the urines of eight patients undergoing methadone therapy is shown to be 0.653 (range: 0.502-0.842). The mean enantiomeric ratio for the metabolite is 0.630 (range: 0.517-0.729). These data document the stereoselectivity of the methadone metabolism. Finally, the EDDP/ methadone ratio is shown to vary between 0.357 and 2.917 with a mean value of 1.731. The capillary electrophoretic assay described is simple, inexpensive and neither requires any sample derivatization, nor large amounts of organic solvents or expensive separation columns.

Cyclodextrins↗

Hemofiltration during cardiopulmonary bypass: quality assessment of hemoconcentrated blood.

UNLABELLED: Hemofiltration is often used during cardiopulmonary bypass (CPB) for water removal. In a prospective random study 11 patients undergoing elective coronary artery surgery with hemofiltration during CPB were observed and compared to 11 patients without filtration. The quantitative and qualitative aspects of blood before and after filtration while still on CPB and until the first postoperative day were assessed. Intra- and postoperative volume requirements, standard hematology and chemistry, as well as hemolysis, complement activation, and coagulation factors were analysed at nine sequential points in time. RESULTS: There were no significant differences in pre- and postoperative patient data between the two groups except that the majority of patients in the study group (55%) were anticoagulated and required a significantly longer CPB time with higher doses of protamine and had higher postoperative drainage (2.9 vs. 1.4 L). Intra- and postoperative hemoglobin concentrations, transfusion and volume requirements were similar in both groups. 927 ml of plasma water were filtered during CPB within 4 min 20 s without hemodynamic changes or electrolyte imbalance. Hemoglobin and protein concentrations increased significantly during hemofiltration (Hb increases 3.6 g/dl). Hemolysis and activated complement fractions were elevated during CPB but showed no further increase during filtration; in contrast C4a, C5a, and prothrombin F1 + 2 increased significantly after cessation of CPB. In conclusion, hemofiltration during CPB is a safe and efficient method for water removal and for concentration of red blood cells and proteins without adverse effects on the patient's hemodynamics, blood quality, and volume requirements. More especially, no negative influence of hemofiltration could be determined with regard to activation of the coagulation and complement system.

Blood Cell Count↗

Classification of depression.

Depression is an aetiologically unspecific reaction pattern of the human organism to psychological or physical changes. It can occur in all forms of psychiatric disorders. The depressive symptomatology in itself does not allow a valid classification. Nosology must take into account aetiology, pathogenesis, and the course. The former two are mostly unknown. Considering the restricted value of all classifications of depressive syndromes the concepts must be validated by external criteria (e.g. genetic, biochemical, neurophysiological criteria, and response to treatment). In this paper a classification based on the course and genetic criteria of depression is proposed. In a preliminary study the clinical diagnoses of 100 depressive patients are compared with the classification based on diagnostic criteria of Feighner et al., Taylor and Abrams, as well as on DSM-III.

Aged↗