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Biomedical subjects

A Müller

Publications and source records attributed to A Müller.

At least 325 records · Page 18Linked to original sources

Microsurgical anatomy of the lateral approach to extraforaminal lumbar disc herniations.

OBJECTIVE: During the "lateral" approach to extraforaminal lumbar disc herniations, the surgeon may be confronted with considerable variations in anatomy, making this approach extremely difficult in some patients. An anatomic study, therefore, was undertaken to examine the bony boundaries of the operative target, the medial intertransverse space. METHODS: In 31 lumbar spine specimens taken from cadavers of people who had been between 30 and 93 years old at death, the relevant distances and proportions of the operative window were measured at the levels L1-L2 to L5-S1. RESULTS: Measurements revealed that the operative window in a systematic fashion becomes progressively smaller as the approach moves from L1-L2 toward L5-S1: 1) from L1 to L5, the medial boundary, the isthmus laminae, gradually extends farther laterally and eventually covers the waist of the respective vertebral body; 2) the lower boundary, the facet joint, gradually overlaps the disc space in an upward and lateral direction; 3) the upper boundary, the transverse process, gradually moves downward. Anatomic variations and abnormalities are found particularly often at the L5-S1 level. CONCLUSION: The anatomic findings led to important conclusions regarding the microsurgical approach to extraforaminal lumbar disc herniations; at levels L1-L2 to L3-L4, the midline approach with lateral retraction of the paraspinal muscles allows for efficient exposure of the lateral neural foramen and avoidance of trauma to the facet joint. Often at level L4-L5, and nearly always at level L5-S1, a tangential route through a paramedian transmuscular approach offers many advantages.

Adult↗

Capsule phase variation in Neisseria meningitidis serogroup B by slipped-strand mispairing in the polysialyltransferase gene (siaD): correlation with bacterial invasion and the outbreak of meningococcal disease.

A mechanism of capsular polysaccharide phase variation in Neisseria meningitidis is described. Meningococcal cells of an encapsulated serogroup B strain were used in invasion assays. Only unencapsulated variants were found to enter epithelial cells. Analysis of one group of capsule-deficient variants indicated that the capsular polysaccharide was re-expressed at a frequency of 10(-3). Measurement of enzymatic activities involved in the biosynthesis of the alpha-2,8 polysialic acid capsule showed that polysialyltransferase (PST) activity was absent in these capsule-negative variants. Nucleotide sequence analysis of siaD revealed an insertion or a deletion of one cytidine residue within a run of (dC)7 residues at position 89, resulting in a frameshift and premature termination of translation. We analysed unencapsulated isolates from carriers and encapsulated case isolates collected during an outbreak of meningococcal disease. Further paired blood-culture isolates and unencapsulated nasopharyngeal isolates from patients with meningococcal meningitis were examined. In all unencapsulated strains analysed we found an insertion or deletion within the oligo-(dC) stretch within siaD, resulting in a frameshift and loss of capsule formation. All encapsulated isolates, however, had seven dC residues at this position, indicating a correlation between capsule phase variation and bacterial invasion and the outbreak of meningococcal disease.

Amino Acid Sequence↗

Evidence for apoptosis of human macrophage-like HL-60 cells by Legionella pneumophila infection.

Legionella pneumophila, the causative agent of Legionnaires' disease and Pontiac fever, replicates within and eventually kills human macrophages. In this study, we show that L. pneumophila is cytotoxic to HL-60 cells, a macrophage-like cell line. We demonstrate that cell death mediated by L. pneumophila occurred at least in part through apoptosis, as shown by changes in nuclear morphology, an increase in the proportion of fragmented host cell DNA, and the typical ladder pattern of DNA fragmentation indicative of apoptosis. We further sought to determine whether potential virulence factors like the metalloprotease and the macrophage infectivity potentiator of L. pneumophila are involved in the induction of apoptosis. None of these factors are essential for the induction of apoptosis in HL-60 cells but may be involved in other cytotoxic mechanisms that lead to accidental cell death (necrosis). The ability of L. pneumophila to promote cell death may be important for the initiation of infection, bacterial survival, and escape from the host immune response. Alternatively, the triggering of apoptosis in response to bacterial infection may have evolved as a means of the host immune system to reduce or inhibit bacterial replication.

Apoptosis↗

Detection of Borna disease virus (BDV) antibodies and BDV RNA in psychiatric patients: evidence for high sequence conservation of human blood-derived BDV RNA.

In several vertebrate species, Borna disease virus (BDV), the prototype of a new group of animal viruses, causes central nervous system disease accompanied by diverse behavioral abnormalities. Seroepidemiological data indicate that BDV may contribute to the pathophysiology of certain human mental disorders. This hypothesis is further supported by the detection of both BDV antigens and BDV RNA in peripheral blood mononuclear cells (PBMCs) of patients with psychiatric disorders and the isolation of BDV from such PBMCs. Here we describe serological and molecular epidemiological studies on psychiatric patients and healthy individuals from the area of Homburg, Germany. Using a novel Western blot (immunoblot) assay, we found a BDV seroprevalence of 9.6% among 416 neuropsychiatric patients, which is significantly higher than the 1.4% found among 203 healthy control individuals. Human sera displayed a prominent immunoreactivity against the virus nucleoprotein, the p40 antigen. Reverse transcriptase-mediated PCR analysis of RNA extracted from PBMCs of a subset of 26 of the neuropsychiatric patients revealed that 50% were BDV RNA positive. Three of the 13 BDV RNA-positive patients also had BDV-positive serology, whereas one patient with serum antibodies to BDV p40 antigen did not harbor detectable BDV RNA in PBMCs. BDV p40 and p24 sequences derived from human PBMCs exhibited both a high degree of inter- and intrapatient conservation and a close genetic relationship to animal-derived BDV sequences.

Adolescent↗

Glutathione transferase activity and formation of macromolecular adducts in two cases of acute methyl bromide poisoning.

OBJECTIVES: To determine the activity of glutathione transferase and to measure the S-methylcysteine adducts in blood proteins, after acute inhalation exposure to methyl bromide. To examine the influence of the polymorphism of glutathione-S-transferase theta (GSTT1) on the neurotoxicity of methyl bromide. METHODS: Two workers acutely exposed to methyl bromide with inadequate respiratory protective devices were poisoned. Seven weeks after the accident, blood samples were drawn from both patients, for measurement of glutathione transferase activity in erythrocytes (conjugator status--that is, GSTT1 phenotype) and measurement of binding products of methyl bromide with blood proteins. Conjugator status was determined by a standard procedure. The binding product of methyl bromide, S-methylcysteine, was measured in globin and albumin. RESULTS: Duration and intensity of exposure were identical for both patients as they worked together with the same protective devices and with similar physical effort. However, one patient had very severe poisoning, whereas the other only developed mild neurotoxic symptoms. The first patient was a "conjugator" with normal glutathone transferase activity, whereas this activity was undetectable in the erythrocytes of the second patient, who consequently had higher concentrations of S-methylcysteine adduct in albumin (149 v 91 nmol/g protein) and in globin (77 v 30 nmol/g protein). CONCLUSIONS: Methyl bromide is genotoxic and neurotoxic. Its genotoxicity seems to be the consequence of the alkylating activity of the parent compound, and conjugation to glutathione has a protective effect. The data presented here suggest a different mechanism for methyl bromide neurotoxicity which could be related to the transformation of methylglutathione into toxic metabolites such as methanethiol and formaldehyde. If such metabolites are the ultimate toxic species, N-acetylcysteine treatment could have a toxifying rather than a detoxifying effect.

Acute Disease↗

1,25-dihydroxyvitamin D3 and the synthetic vitamin D analogue, KH 1060, modulate the growth of mouse proximal tubular cells.

Apart from its classical role in bone and mineral metabolism, 1,25-dihydroxyvitamin D3 (1,25-vitamin D3) has recently been shown to affect cell growth and differentiation from a variety of tissues primarily not involved in mineral metabolism and to provide immunomodulatory functions. Findings in human mesangial cells in vitro as well as in rat model of compensatory renal growth in vivo suggest that renal cells are a target for 1,25-vitamin D3. In the present study the effects of 1,25-vitamin D3 and a synthetic vitamin D analogue, KH 1060, on proliferation and protein synthesis were investigated in a mouse proximal tubular cell line (MCT). 1,25-vitamin D3 and KH 1060 inhibited cell proliferation dose dependently (10(-7) to 10(-12) M) and specifically as assessed by 3H-thymidine incorporation (DNA synthesis) and cell counting. The cellular protein concentration, protein synthesis (3H-methionine incorporation) and protein/DNA ratio were not influenced by 1,25-vitamin D3 and KH 1060. By analyzing c-fos and c-myc expression using semiquantitative RT-PCR, a constant basal expression of both protooncogenes, even under serum-free conditions, was found in MCT cells. Phorbol 12-myristate 13-acetate (TPA) further stimulated c-fos and c-myc expression, whereas treatment with 1,25-vitamin D3 (10(-7) M) it had no effect either in unstimulated or in TPA-stimulated cells. In conclusion, 1,25-vitamin D3 and a synthetic vitamin D analogue, KH 1060, provide growth-regulating effects on renal proximal tubular cells in vitro. These effects are not mediated by regulation of c-fos and c-myc. Further studies will have to clarify whether 1,25-vitamin D3 plays a physiologic role in renal development and growth in vivo.

Animals↗

Uvitex 2B stain for the diagnosis of Isospora belli infections in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: Fluorescent stains with Uvitex 2B or other fluorochromes are widely used today, especially for the diagnosis of microsporidian infections in human immunodeficiency virus (HIV)-infected patients. Our objective was to ascertain whether the fluorescent stain with Uvitex 2B is also able to detect Isospora belli in stool samples and duodenal/bile juice of HIV-infected patients. DESIGN: Case study. SETTING: University hospital of the University of Cologne, Germany. PATIENTS: Two HIV-infected patients with chronic diarrhea who had intestinal infections with I. belli. METHODS: Stool was concentrated by a modified water-ether sedimentation method, and duodenal/bile juice was concentrated by centrifugation. Wet-mount preparations were examined by phase-contrast and bright-field microscopy, and smears were stained with a modified acid-fast stain and a fluorescent stain with Uvitex 2B. RESULTS: Using the fluorescent stain with Uvitex 2B, the oocysts of I. belli stained bright white/blue fluorescent and showed a structure similar to that of the oocysts in acidfast stains. CONCLUSIONS: Staining with Uvitex 2B is a suitable method for the diagnosis of I. belli infections. This technique can be used for the diagnosis of three important gastrointestinal parasites (viz, microsporidia, cryptosporidia, and I. belli) responsible for diarrhea in HIV-infected patients.

AIDS-Related Opportunistic Infections↗

-Value of activated blood coagulation time in monitoring anticoagulation during coronary angioplasty-.

Accurate heparin anticoagulation assessment is important to prevent complications (hemorrhage, thrombotic coronary occlusion) during and after coronary angioplasty (PTCA). Paired ACT-, aPTT- and prothrombin time (PT) measurements have not been studied after PTCA using a high dose heparin management. For that reason we analyzed in 150 consecutive patients (115 m., 35 f., 61 +/- 10 y.) immediately after PTCA and at the time of arterial sheath removal aPTT-(Neothromtin, Behring), PT- (Thromborel S, Behring) and ACT-(HR-ACT, HemoTec) values after application of 20,000 U of heparin (5,000 U intravenous, 15,000 U intracoronary) followed by a heparin-infusion (15,000-25,000 U/24 h). Immediately after PTCA in all patients a aPTT above the upper limit of >180 s was found. The average postprocedural ACT was 330 +/- 82 s. Only 9 patients showed an ACT below 200 s. All coronary reocclusions (n = 3) immediately after PTCA occurred in this group. Arterial sheaths were removed 13 +/- 3 h after PTCA. The incidence of minor peripheral bleeding complications at that time was 21% and was related to the anticoagulation level. Major bleeding complications requiring transfusion were noted in only one case. Our findings suggest that after high dose heparinization for PTCA the ACT test provides a reliable and broad range for the assessment of heparin anticoagulation. In contrast to the aPTT the ACT is ideally suited to determine the dosage of heparin infusion and the time of arterial sheath removal after PTCA. ACT measurements are superior to aPTT measurements in heparin anticoagulation assessment during and direct after PTCA.

Aged↗

[Reinterventions in secondary incontinence].

Overlapping sphincter reconstruction for fecal incontinence due to perineal tears, trauma or iatrogenic injuries is the therapy of choice. If this technique fails repeatedly or more than half of the sphincter is destroyed, a gracilis muscle plasty is indicated. Incontinence caused by an ectropion must be treated by a skin flap procedure (Ferguson or VY-plasty). These techniques are described in detail. Results of 54 overlapping procedures carried out in 47 patients (30 females, 17 males, age 15-84, median 47 years) during the last 3.5 years are presented. The most frequent cause of incontinence was fistulectomy followed by perineal tears. Thirty-day success rate with excellent or good results (difficulty in controlling flatus) was 82%, decreasing to 70% at the end of follow-up. Complications were rare (7/54) and did not influence outcome except for wound healing by second intention, which resulted in a high failure rate. Superior results were achieved when the reason for incontinence was a perineal tear (81%, compared with fistulectomy (64%). In conclusion, overlapping sphincter reconstruction results in a high success rate, especially when fecal incontinence was caused by a perineal tear.

Adolescent↗

[Coping with stress and self-awareness in idiopathic sudden deafness].

In the work presented here patterns of stress management and self awareness of patients with sudden hearing loss (n = 50) are studied and compared to a control group. Private self awareness is conceived as a moderator of stress management. Data analysis was performed with special consideration given to gender specificity of patterns investigated. The profile of stress management in patients with sudden hearing loss differs from control groups. As for stress management, gender specific data analysis reveals for male as well as for female patients significant differences when compared to control groups. Beyond that, profiles of stress management differ between males and females. Furthermore, private self awareness in patients with sudden hearing loss exhibit significant differences in mean values when compared to control groups, which is interpreted as a reflection of a lower prevalence of private self awareness. However, gender specific analysis supports this initially significant result only to have tendentious character. With respect to preventive treatment and prophylaxis of relapse, our results suggest that training in stress management should be completed by bodily oriented procedures suited to enhance the perception of body signals.

Adaptation, Psychological↗

Evaluation of a gp 55 (E2) recombinant-based ELISA for the detection of antibodies induced by classical swine fever virus.

An enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against classical swine fever virus (CSFV) based on the competition of the serum antibodies with a CSFV-specific monoclonal antibody directed against the viral glycoprotein gp 55 (E2), has been evaluated. A total of 553 sera obtained from pigs experimentally infected in groups with different pestiviruses were included in this study. The ELISA was applied to a group of sera collected from pigs prior to pestivirus inoculation and therefore expected to have no detectable CSFV neutralizing antibodies. The specificity of the ELISA was calculated to range between 93% and 98%. The sensitivity of the ELISA was determined by testing predominantly sera of pigs exposed to CSFV and exhibiting CSFV neutralizing antibodies. When the cut-off level was reduced by 10%, the average sensitivity increased from 60% to 70% for the groups of sera tested. The ELISA was able to discriminate between CSFV and bovine viral diarrhoea virus (BVDV) induced antibodies.

Animals↗

[Bioavailability of two verapamil formulations following repeated administration in steady-state conditions. An open, two-period, crossover study].

The relative bioavailability of a new formulation of verapamil (CAS 52-53-9, Veramex 40) in comparison to a standard formulation was investigated in an open two-period cross-over study in 16 healthy volunteers under steady state conditions of 7 days duration each. For the estimation of verapamil a selective HPLC-method was used with fluorescence detection after direct injection and enrichment by column switching enabling a simultaneous separation and analysis of verapamil and N-norverapamil. The bioavailability was estimated using areas under the concentration-time curves (AUC), maximum serum concentrations (Cmax) and peak-trough fluctuation (PTF). Bioequivalence was tested calculating the 90% confidence intervals (ANOVAlog). The mean verapamil plasma profile after the test substance was up to 1.5 h slightly lower than the corresponding curve after the reference substance, thereafter slightly higher plasma levels up to 7 h were observed after the test substance. The individual plasma profiles had a similar variance, and hardly any difference was discernible between the two drugs. A similar behaviour was also seen for N-norverapamil. A mean relative bioavailability of 101% was observed after the test substance both for verapamil and N-norverapamil. The mean maximum plasma concentrations for verapamil and N-norverapamil were 50.0 and 49.7 ng/ml, respectively. After the standard formulation the corresponding values were 50.4 and 50.3 ng/ml. The mean PTF-values for verapamil and N-norverapamil were 178 and 76.6% after the test substance and 182 and 79.6% after the standard formulation, respectively. The 90% confidence intervals for AUC, Cmax and PTF for verapamil and N-norverapamil are completely within the accepted range of 80 to 125% for AUC, Cmax and PTF. Therefore bioequivalence between both formulations can be stated.

Adult↗

[Cement-free management of femoral neck fractures in elderly patients with poor cardiopulmonary prognosis].

The use of acrylic bone cement in the treatment of femoral neck fractures with prosthetic implants is associated with a high complication rate in patients suffering from cardiopulmonary problems. This type of patient can be treated with a cementless hip prosthesis without the danger of a cardiovascular depression occurring. The cementless operating technique produces a good primary stability even where bone quality is poor and, therefore, immediate post-operative limitations on weight bearing are not required.

Acrylic Resins↗

The molybdenum nitrogenase from wild-type Xanthobacter autotrophicus exhibits properties reminiscent of alternative nitrogenases.

In the presence of molybdate (1 microM) 2-3.5% oxygen and with sucrose as carbon source, Xanthobacter autotrophicus GZ29, a microaerophilic nitrogen-fixing hydrogen-oxidizing bacterium, grew diazotrophically with a minimal doubling time of 2.5 h and a calculated absorbance of up to 52 (546 nm). The maximal specific activity obtained was 145 nmol ethylene reduced . min-1 . mg protein-1 (crude extract). The Mo nitrogenase was derepressed to a comparable level with methionine as nitrogen source. Vanadium compounds stimulated neither growth nor nitrogenase activity. Without added molybdate, diazotrophic growth and nitrogenase activity decreased to an extremely low level. The nitrogenase, responsible for the residual activity in molybdate-starved cells, contained molybdate but no other heterometal atom. These results indicate that, in X. autotrophicus, a Mo-independent nitrogenase does not exist. However, the molybdate-containing nitrogenase exhibited some properties which are reminiscent of alternative nitrogenases. The MoFe protein (component 1, Xa1) copurified with two molecules of a small, not previously detected polypeptide (molar mass 13.6 kDa) and was able to reduce acetylene not only to ethylene but also partly to ethane. Under certain conditions, i.e. in Tris/HCl buffer at alkaline pH values, with titanium (III) citrate as electron donor, at high component 1/component 2 ratios, and at low, non-saturating acetylene concentrations, up to 5.5% ethane was measured. Parallel to the pH-dependent increase of the relative yield of ethane, the total activity (both acetylene and nitrogen reduction rates) decreased and the S = 3/2 FeMo cofactor ESR signal was split into three signals with different rhombicities [E/D values of 0.036 (signal I), 0.072 (signal II) and 0.11 (signal III)]. The intensities of the two new FeMo cofactor signals were more pronounced the more alkaline the pH. They could be further enhanced using titanium (III) citrate instead of Na2S2O4 as reductant.

Catalysis↗

Comparison of the carbohydrate biological response modifiers Krestin, schizophyllan and glucan phosphate by aqueous size exclusion chromatography with in-line argon-ion multi-angle laser light scattering photometry and differential viscometry detectors.

A major barrier to the development, preclinical and clinical application of natural carbohydrate biological response modifiers has been the difficulty involved in accurately characterizing carbohydrate polymers with molecular masses ranging from 10(4) to 10(7) g/mol. Herein, we employed size exclusion chromatography with multi-angle laser light scattering and differential viscometry to compare and contrast structural properties of the biological response modifiers Krestin, schizophyllan and glucan phosphate. Krestin, schizophyllan and glucan phosphate exhibit significant differences in molecular mass moments, molecular mass distribution, polymer sizes, intrinsic viscosity and perhaps their solution behaviour. This knowledge of precise physicochemical data is required for a better understanding of the properties and higher structure of complex carbohydrate biological response modifiers.

Chromatography, Gel↗

Transesterification reactions of parabens (alkyl 4-hydroxybenzoates) with polyols in aqueous solution.

Accelerated stability tests of aqueous solutions containing parabens and polyols were performed using concentrations similar to pharmaceutical and cosmetic formulations. Reaction products were detected in these solutions by HPLC and identified by chromatographic and spectroscopic means. Using xylitol and methylparaben as model reactants, three unknown peaks having the relation 1:2:4 were obtained together with the hydrolysis product 4-hydroxybenzoic acid. Diode array detection gave identical UV spectra for each peak with a maximum at 255 nm. The structures of the isomeric 1-, 2-, and 3-xylityl 4-hydroxybenzoic acid esters were proved by means of LC-MS, GC-MS, and NMR and correlated to the peaks in the HPLC chromatograms. The rate of the transesterification was shown to be highest in strongly alkaline medium (ph 10-11), whereas equilibration of the reaction was optimally balanced at pH 8-9. An increase of polyol concentration enhanced the formation of the esters. The reactivity of different substituted parabens was higher in the case of parabens with a short alkyl ester function. Similar reaction profiles were observed with C3-C6 polyols, but no transesterification took place when aldoses were used.

Chromatography, High Pressure Liquid↗

Immediate metabolic effects of different nutritional regimens in critically ill medical patients.

OBJECTIVE: Metabolic effects of different caloric regimens were investigated in nonsurgical, medical patients with multiple-organ failure (MOF). DESIGN: Seven total parenteral nutrition (TPN) regimens were administered, differing in amount (14, 28, and 56 kcal/kg per day, i.e., hypo-, iso-, and hypercaloric nutrition, respectively) and distribution [carbohydrates (COH), amino acids (AA), long-chain and medium-chain triglycerides (LCT/MCT)] of calories. Each regimen was administered over 12 h. Metabolism was monitored by energy expenditure (EE), body temperature (BT), protein breakdown (PB), and blood glucose and serum lactate levels. Measurements were started within 2 days of MOF onset. SETTING: The study was conducted in a medical intensive care unit. PATIENTS: Twenty patients with MOF on mechanical ventilation (mean Apache II score x = 26) were investigated. MEASUREMENTS AND RESULTS: The mean values of the EE (x = 31 kcal/kg per day), BT (x = 38 degrees C), PB (x = 1.5 g/kg per day), and lactate (x = 2.0 mmol/l) and glucose level (x = 222 mg/dl) parameters were elevated. EE, BT, and lactate and glucose levels were significantly lower under hypocaloric nutrition than during iso- and hypercaloric nutrition (p < 0.01). Differences in the metabolic effects of LCT and MCT were not significant. PB was significantly elevated under hypercaloric nutrition (p < 0.01). Protein balance was positive under hypercaloric nutrition, and negative under iso- and hypocaloric nutrition. CONCLUSIONS: In nonsurgical, medical patients neither hypercaloric nor isocaloric nutritional support prevented protein catabolism; in contrast, they enhanced the metabolic burden measured by EE, thermogenesis, urea production rate, and glucose and lactate levels. A hypocaloric regimen is therefore recommended for these patients during the early phase of MOF.

Aged↗