Treating hypertensive patients with intracranial pathology.
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Antihypertensive Agents↗
Biomedical subjects
M Müller
Publications and source records attributed to M Müller.
Sequence conservation within the major capsid protein of human papillomavirus (HPV) type 18 and formation of HPV-18 virus-like particles in Saccharomyces cerevisiae.
The major capsid protein L1 of human papillomaviruses (HPVs) has been identified as a promising candidate antigen for a prophylactic HPV vaccine. Since amino acid sequence heterogeneity has been demonstrated for the L1 genes within individual HPV types, nucleotide sequences of L1 were determined from six HPV-18 clinical isolates and the cervical carcinoma cell line SW756 and compared to the published HPV-18 prototype sequence. The sequences were almost identical between the clinical isolates and SW756 but differed markedly from the published prototype sequence. Resequencing the prototype HPV-18 revealed that these differences were due to sequencing artifacts of the prototype HPV-18 sequence archived in GenBank. Thus, the HPV-18 L1 genes seem to display a very high level of sequence conservation. The HPV-18 L1 gene derived from SW756 was expressed in Saccharomyces cerevisiae and self-assembly of the L1 protein into virus-like particles was demonstrated.
Base Sequence↗
Antibodies to human papillomavirus type 11 virus-like particles in sera of patients with genital warts and in control groups.
We analysed by ELISA a total of 478 human sera for the presence of antibodies to HPV-11 virus-like particles. The sera were obtained from patients with current genital warts (group CO), from males attending the hospital for fertility disorders (group MA), from blood donors (group BD) and from patients hospitalized for reasons unrelated to HPV infections (group HO). Antibody prevalence was higher in male patients of group CO (23.0%) as compared to males of groups MA (3.2%; P < 0.0001), HO (5.3%; P = 0.01) and BD (16.7%; NS). In addition, there was a significant difference in antibody titre between the males of group CO compared to group MA. Within the whole sample the absorbance of sera from females was higher than in specimens from males (P < 0.0001). A small subset of the sera was also tested by radioimmunoprecipitation assay (RIPA). There was good agreement between the data obtained by ELISA and RIPA.
Adolescent↗
Quantum-mechanical description of charged particles with spin 1/2 in the magnetic field outside of a rectilinear current filament.
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Journal Article↗
Resonance phenomena near thresholds.
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Journal Article↗
Topological effects in ring polymers: A computer simulation study.
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Journal Article↗
Cardiovascular effects of desflurane and isoflurane in patients with coronary artery disease.
BACKGROUND: Anaesthesia in patients with ischaemic heart disease may cause adverse haemodynamic reactions. This investigation compares the cardiovascular effects of equipotent concentrations of desflurane and isoflurane in 30 patients (ASA III) with coronary artery disease before surgical stimulation. METHODS: After standardised induction of anaesthesia with etomidate, fentanyl and pancuronium and tracheal intubation patients randomly received either desflurane (group I, n = 15) or isoflurane (group II, n = 15) in slowly increasing concentrations. ST-segment analysis and haemodynamic measurements were performed at 0.25, 0.5, 0.75 and 1.0 MAC of desflurane or isoflurane. RESULTS: Cardiac index did not change significantly in the two groups during the administration of the inhalational anaesthetics. Desflurane and isoflurane both caused a dose-dependent significant decrease of mean arterial blood pressure (group I: -16%; group II: -18%). As with isoflurane, the decrease of mean arterial pressure produced by desflurane primarily resulted from a decrease in systemic vascular resistance (group I: -26%, group II: -21%). Central venous pressure was not affected by the two volatile anaesthetics. Pulmonary artery pressure and pulmonary capillary wedge pressure remained unchanged during the administration of isoflurane, but in contrast both parameters significantly increased in patients receiving desflurane (PAP 24%, PCWP 40%). ST-segment analysis provided no signs of myocardial ischaemia. CONCLUSION: The results of this study demonstrate that in patients with coronary artery disease the haemodynamic effects of equipotent concentrations of desflurane and isoflurane are similar except for a significant increase in PAP and PCWP caused by desflurane. Therefore, desflurane should be administered with great caution if it is used as an alternative anaesthetic in patients with ischaemic heart disease.
Adult↗
Cerebral hemodynamics in the posterior circulation of patients with bacterial meningitis.
OBJECTIVES: Stenoses of the middle and anterior cerebral artery (MCA,ACA) are a clinical relevant complication of bacterial meningitis. We examined the involvement of the posterior cerebral (PCA) and of the basilar artery (BA) into the inflammatory process. MATERIAL & METHODS: 39 unselected patients (26 men, 13 women; mean +/- SD age, 49 +/- 17 years) with bacterial (n = 37) and fungal (n = 2) meningitis underwent serial transcranial Doppler sonography recordings of the mean blood velocity (MBV) and the pulsatility index (PI) in the MCA, ACA and PCA, in the BA and in the submandibular internal carotid artery on Days 1, 3, 5, 8, 14 and 21 after admission. The results of the PCA and of the BA were compared to normal reference values and correlated to corresponding neurological signs. The criterion to assume a stenosis was: for the BA an MBV > or = 95 cm/s, for the PCA an MBV > or = 85 cm/s. RESULTS: Compared with the controls MBV in both arteries was normal on Days 1 and 8-21, but significantly increased on Days 3 and 5. The PI was significantly increased in the BA on all days and in the PCA on Days 1 and 8-21. Stenoses of the PCA (4 of 43) and of the BA (4 of 32) remained without corresponding neurological signs, and occurred only in patients with two or more narrowed arteries of the anterior circulation (p < 0.05). CONCLUSION: In bacterial meningitis, hemodynamic disturbances in the posterior circulation are less severe than in the anterior circulation and are clinically well tolerated.
Adolescent↗
Characterization of peripheral-compartment kinetics of antibiotics by in vivo microdialysis in humans.
The calculation of pharmacokinetic/pharmacodynamic surrogates from concentrations in serum has been shown to yield important information for the evaluation of antibiotic regimens. Calculations based on concentrations in serum, however, may not necessarily be appropriate for peripheral-compartment infections. The aim of the present study was to apply the microdialysis technique for the study of the peripheral-compartment pharmacokinetics of select antibiotics in humans. Microdialysis probes were inserted into the skeletal muscle and adipose tissue of healthy volunteers and into inflamed and noninflamed dermis of patients with cellulitis. Thereafter, volunteers received either cefodizime (2,000 mg as an intravenous bolus; n = 6), cefpirome (2,000 mg as an intravenous bolus; n = 6), fleroxacin (400 mg orally n = 6), or dirithromycin (250 mg orally; n = 4); the patients received phenoxymethylpenicillin (4.5 x 10(6) U orally; n = 3). Complete concentration-versus-time profiles for serum and tissues could be obtained for all compounds. Major pharmacokinetic parameters (elimination half-life, peak concentration in serum, time to peak concentration, area under the concentration-time curve [AUC], and AUC/MIC ratio) were calculated for tissues. For cefodizime and cefpirome, the AUCtissue/AUCserum ratios were 0.12 to 0.35 and 1.20 to 1.79, respectively. The AUCtissue/AUCserum ratios were 0.34 to 0.38 for fleroxacin and 0.42 to 0.49 for dirithromycin. There was no visible difference in the time course of phenoxymethylpenicillin in inflamed and noninflamed dermis. We demonstrated, by means of microdialysis, that the concept of pharmacokinetic/pharmacodynamic surrogate markers for evaluation of antibiotic regimens originally developed for serum pharmacokinetics can be extended to peripheral-tissue pharmacokinetics. This novel information may be useful for the rational development of dosage schedules and may improve predictions regarding therapeutic outcome.
Adipose Tissue↗
Involvement of the GroE chaperonins in the nickel-dependent anaerobic biosynthesis of NiFe-hydrogenases of Escherichia coli.
We analyzed the involvement of chaperonins GroES and GroEL in the biosynthesis of the three hydrogenase isoenzymes, HYD1, HYD2, and HYD3, of Escherichia coli. These hydrogenases are NiFe-containing, membrane-bound enzymes composed of small and large subunits, each of which is proteolytically processed during biosynthesis. Total hydrogenase activity was found to be reduced by up to 60% in groES and groEL thermosensitive mutant strains. This effect was specific because it was not seen for another oligomeric, membrane-bound metalloenzyme, i.e., nitrate reductase. Analyses of the single hydrogenase isoenzymes revealed that a temperature shift during the growth of groE mutants led to an absence of HYD1 activity and to an accumulation of the precursor of the large subunit of HYD3, whereas only marginal effects on the processing of HYD2 and its activity were observed under these conditions. A decrease in total hydrogenase activity, together with accumulation of the precursors of the large subunits of HYD2 and HYD3, was also found to occur in a nickel uptake mutant (nik). The phenotype of this nik mutant was suppressed by supplementation of the growth medium with nickel ions. On the contrary, Ni2+ no longer restored hydrogenase activity and processing of the large subunit of HYD3 when the nik and groE mutations were combined in one strain. This finding suggests the involvement of these chaperonins in the biosynthesis of a functional HYD3 isoenzyme via the incorporation of nickel. In agreement with these in vivo results, we demonstrated a specific binding of GroEL to the precursor of the large subunit of HYD3 in vitro. Collectively, our results are consistent with chaperonin-dependent incorporation of nickel into the precursor of the large subunit of HYD3 as a prerequisite of its proteolytic processing and the acquisition of enzymatic activity.
Amino Acid Sequence↗
DNA encapsidation by viruslike particles assembled in insect cells from the major capsid protein VP1 of B-lymphotropic papovavirus.
Capsids of polyomaviruses--small, nonenveloped DNA viruses--consist of the major structural protein VP1 and the minor structural proteins VP2 and VP3. The contributions of the individual capsid proteins to functions of the viral particle, such as DNA encapsidation, cell receptor attachment, entry, and uncoating, are still not clear. Here we show that viruslike particles assembled in nuclei of insect cells from VP1 of the monkey B-lymphotropic papovavirus (LPV) are sufficient to unspecifically encapsidate DNA. LPV VP1 expressed in large amounts in insect cells by a baculovirus vector assembled spontaneously in the nuclei to form viruslike particles. After metrizamide equilibrium density gradient purification and nuclease digestion, a fraction of these particles was shown to contain VP1-associated linear, double-stranded DNA with a predominant size of 4.5 kb. The fraction of DNA-containing VP1 particles increased with time and dose of baculovirus vector infection. The DNA-containing particles, further purified by sucrose gradient centrifugation, appeared as "full" particles in negative-staining electron microscopy. As shown by DNA hybridization, the encapsidated DNA consisted of insect cell and baculoviral sequences with no apparent strong homology to LPV sequences. Three non-LPV VP1-derived host proteins with apparent molecular masses of approximately 14, 15, and 16 kDa copurified with the DNA-containing particles and may represent insect cell histones encapsidated together with the DNA. A similar species of host DNA was also found in purified LPV wild-type virions. These data suggest that LPV VP1 alone can be sufficient to encapsidate linear DNA in a sequence-independent manner.
Animals↗
Measurement of interstitial muscle glucose and lactate concentrations during an oral glucose tolerance test.
To study the relationship between blood flow rate and muscle metabolism, muscle microdialysis was performed in nine human subjects (5 females and 4 males) after an oral glucose load (75 g). Two microdialysis probes were inserted into the medial femoral muscle for estimation of glucose and lactate concentrations in the interstitial fluid, and the muscle blood flow was measured concomitantly with strain-gauge plethysmography. After subjects fasted overnight, their glucose concentration in arterial plasma and interstitial fluid was 4.6 +/- 0.13 vs. 3.8 +/- 0.23 mmol/l (P < 0.05), and the corresponding lactate concentrations were 0.60 +/- 0.07 vs. 0.83 +/- 0.07 mmol/l (P < 0.05). Muscle blood flow was 5.2 +/- 0.7 and 7.5 +/- 1.4 ml.100 g-1.min-1 (P < 0.05) at 0 and 90 min after oral glucose, respectively. The arterial-interstitial concentration differences of glucose increased after oral glucose [at 0 min 0.73 +/- 0.24 vs. 2.19 +/- 0.60 mmol/l at 90 min (P < 0.001)]. The corresponding values for lactate were -0.23 +/- 0.10 at 0 min vs.-0.26 +/- 0.18 mmol/l at 90 min (not significant). The data show that 1) the capillary wall is partly rate limiting for glucose uptake, and 2) after oral glucose, the glucose concentration gradient over the capillary wall increases despite a limited increase in blood flow rate, which then mediates approximately 10-20% of total enhancement of glucose uptake in muscle.
Adult↗
Vasomotor reactivity and pattern of collateral blood flow in severe occlusive carotid artery disease.
BACKGROUND AND PURPOSE: The compromise of cerebrovascular autoregulation in severe occlusive carotid artery disease depends on the functional capacity of collateral pathways. In previous reports correlating hemodynamic disturbances with collateral pathways, collateral blood supply was often evaluated by invasive cerebral angiography. In this study noninvasive transcranial Doppler ultrasound was used to determine both collateral pathways and vasomotor reactivity. METHODS: With the use of blood flow direction, compression tests, and evident side-to-side asymmetries of blood velocities, the collateral supply through the anterior and posterior communicating arteries, the ophthalmic artery, and leptomeningeal anastomoses was evaluated by transcranial Doppler ultrasound in 48 patients (42 men, 6 women; mean +/- SD age, 59 +/- 9 years) with occlusion (n = 36) or stenosis of more than 90% (n = 12) of one internal carotid artery. Ipsilateral vasomotor reactivity was determined by the percent increase of middle cerebral artery mean blood velocity with the use of (1) the breath-holding maneuver and (2) acetazolamide (1 g IV) as vasodilatory stimulus. Additional stenoses (50% to < 90%) of the contralateral internal carotid artery were present in 20 of the 48 patients. RESULTS: Vasomotor reactivity was not affected by the presence of a contralateral internal carotid artery stenosis. Both vasodilatory stimuli similarly indicated poor vasomotor reactivity when an ophthalmic or a leptomeningeal pathway accompanied an anterior communicating artery pathway compared with a lone anterior communicating artery pathway (P < .05). The acetazolamide challenge indicated significantly better preserved vasomotor reactivity when blood supply was provided through a lone anterior communicating artery pathway (66 +/- 30%) than through an anterior and posterior communicating artery pathway (33 +/- 20%, P < .05), whereas the breathholding method failed to show such a difference. CONCLUSIONS: The presence of an ophthalmic artery pathway may provide the first evidence of disturbed vasomotor reactivity. The use of cerebral angiography to evaluate collateral pathways must be considered carefully since transcranial Doppler ultrasound is a reliable noninvasive alternative.
Acetazolamide↗
Expression domains of a zebrafish homologue of the Drosophila pair-rule gene hairy correspond to primordia of alternating somites.
her1 is a zebrafish cDNA encoding a bHLH protein with all features characteristic of members of the Drosophila HAIRY-E(SPL) family. During late gastrulation stages, her1 is expressed in the epibolic margin and in two distinct transverse bands of hypoblastic cells behind the epibolic front. After completion of epiboly, this pattern persists essentially unchanged through postgastrulation stages; the marginal domain is incorporated in the tail bud and, depending on the time point, either two or three paired bands of expressing cells are present within the paraxial presomitic mesoderm separated by regions devoid of transcripts. Labelling of cells within the her1 expression domains with fluorescein-dextran shows that the cells in the epibolic margin and the tail bud are not allocated to particular somites. However, allocation of cells to somites occurs between the marginal expression domain and the first expression band, anterior to it. Moreover, the her1 bands, and the intervening non-expressing zones, each represents the primordium of a somite. This expression pattern is highly reminiscent of that of Drosophila pair-rule genes. A possible participation of her1 in functions related to somite formation is discussed.
Animals↗
Computer assisted determination of the dose-area product in retrograde urethrography.
Retrograde urethrography (RUG) is a dynamic radiological procedure in which the cumulative dose-area product (DAP) comprises radiation doses derived from both fluoroscopy and radiography. In the present prospective study, digital retrograde urethrographs (Prestilix 1600X/DRS, General Electric) were obtained in 40 consecutive male patients (mean age 60.6 years; range 23-88 years) presenting for evaluation of urinary pathology. The radiation dose was recorded as the dose-area product. From these data, a computer program (Diasoft 2.0, PTW, Freiburg, Germany) then determined the respective proportions of the total radiation dose deriving from fluoroscopy and radiography, as well as the number of radiographic exposures. The average total radiation dose was 316 cGy cm2. In five of the 40 patients examined (12.5%), the number of radiographic exposures registered by the program and, hence, the calculated DAPs were erroneous. In the remaining 35 patients, the average proportion of the cumulative DAP resulting from fluoroscopy was 81%, while that deriving from radiography was 19%. The computer program utilized in this study makes possible an intelligent evaluation of the DAP in dynamic procedures such as RUG. Since fluoroscopy is responsible for 81% of the cumulative DAP at RUG, a significant decrease in applied radiation dose may be achieved by reducing fluoroscopy time or by using pulsed fluoroscopy.
Adult↗
Light damage in rod outer segments: the effects of fixation on ultrastructural alterations.
PURPOSE: In this electron microscopical study, we compared effects of chemical fixation versus cryofixation on the ultrastructure of acute rod outer segment alterations in the rat retina. METHODS: The alterations were induced by toxic levels of diffuse white light. Albino rats were exposed to 2000 lux for 30 min. Samples from one eye of each animal were fixed by high pressure freezing and samples from the other eye were fixed by standard glutaraldehyde procedures. RESULTS: Light exposed retina showed major differences in their rod outer segments, inner segments and photoreceptor synaptic regions in chemical fixation. In particular gross vesiculations of outer segment membranes were produced in light exposed experiments. In contrast, in cryo-fixed samples such prominent changes were not observed in outer segment membranes. There was, however, occasional formation of small vesicles and a reduction of the cilium diameter in response to light damage. In the dark adapted control group the morphology of chemically fixed and cryo-fixed photoreceptors was similar. CONCLUSIONS: We conclude, that cryo-fixed samples better represent the living state of the retina, because high pressure freezing is a purely physical method and acts much faster than chemical fixation.
Animals↗
[Traveling on the data highway--online information for urologists].
Global exchange of information is one of the major sources of scientific progress in medicine. Electronic media have recently supplemented the standard methods of scientific communication such as congresses, books and journals. Currently, 30 million computers are part of the world-wide, exponentially growing network, the ""information superhighway''. Numerous resources offered by the network are becoming increasingly useful in clinical medicine. In Germany, three major networks are currently available: T-Online/Datex-J, Compuserve and Internet. The majority of information relevant to urologists can be found in the Internet. This information includes medical journals that can either partly or completely be read online, online library catalogs, scientific images (pathology and radiology), and databases on urologic oncology and basic research in urology. Even outside academic institutions access to the "information superhighway" is easily available. Currently, the "information superhighway" constitutes a new source of database-type information; in the near future, medical education, clinical consultation and worldwide cooperation in clinical studies will be new fields of scientific communication employing worldwide computer networks.
Forecasting↗
[The revised PEDINFUS computer program for total and added parenteral nutrition in children].
The computer program PEDINFUS, first described in 1991, has been fundamentally revised and further developed. The area of application has been considerably widened as additive parenteral nutrition has been included and the group of newborn and preterm infants has been taken into account. Consequently, the program can be used for children of all age groups. In addition, the program has a graphical user interface and can be used on several hardware platforms. The flexibility of the program has also been increased to a considerable degree. Now the nutrient amounts per kilogram per day, the limits of the laboratory values, the combination of enteral food and infusion solutions, and the already drawn-up infusion plans can be changed at liberty. Considerably more matters of clinical interest accompanying parenteral nutrition have been integrated in the program. Further plausibility controls have also been introduced to achieve greater certainty in the calculation of the infusion solutions. In consequence, the preconditions for ensuring and controlling the quality of infusion therapy regimens can be established on an improved level.
Adolescent↗