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Biomedical subjects

G Pfeiffer

Publications and source records attributed to G Pfeiffer.

At least 37 records · Page 2Linked to original sources

Spectral analysis of heart rate and blood pressure in Guillain-Barré patients with respiratory failure.

The clinical value of heart rate and blood pressure variation (HRV and BPV) spectra was assessed in 11 consecutive patients with Guillain-Barré syndrome (GBS) on artificial ventilation. Their HRV and BPV spectra were compared with those from 28 control intensive care unit (ICU) patients without peripheral nerve disorders. ICU controls had low respiratory HRV during controlled ventilation. If present, it was closely related to, but smaller than BPV, suggesting baroreceptor reflex mediation. Respiratory HRV similar to that of healthy controls was observed only in ICU controls with significant spontaneous ventilation. HRV was prominent in a subgroup of GBS patients who suffered from bradycardia or sinus arrest, whereas GBS patients without episodic bradycardia only exceptionally had respiratory HRV. Interpretation of HRV during artificial ventilation cannot be extrapolated from experience with spontaneously breathing subjects. In contrast to diabetic neuropathy, not loss, but preservation of respiratory HRV was ominous in artificially ventilated GBS patients. A pattern of prominent broad respiratory HRV peaks and narrow BPV peaks occurred only in GBS and forebode sinus arrest.

Adult↗

[Type I Charcot-Marie-Tooth syndrome. Disability and management].

Molecular genetic research on Charcot-Marie-Tooth 1 syndrome (CMT 1) progresses rapidly, still obviously no cure is available for affected individuals. Our aim was to investigate current management in clinical CMT 1 50 patients with Charcot-Marie-Tooth syndrome type I (CMT 1) were explored for applied means of therapy and use of health care institutions. We documented the number of annual appointments at a neurologist, orthopaedist and psychologist. Previous admissions to hospitals and rehabilitation centres and surgical procedures were assessed. Practice of physiotherapy, occupational and physical therapy were investigated, also administered orthopaedic devices, mechanical devices and technical modification of car and home. Drugs prescribed were listed and the number of patients seeking advice at para-medical institutions was determined. Degree of medical support did not correlate with severity of disease. We observed that persons with marked disability did not uniformly receive adequate therapy. This was partly due to the responsible physicians, and partly due to lacking cooperation of the patients. Support of affected individuals and counselling to our opinion are to be improved. This would require further evaluation of therapies, establishment and distribution of guidelines, as well as motivation of patients, which might be facilitated by the offer of molecular genetic diagnostics.

Adolescent↗

Orthotopic implantation of inflamed synovial tissue from RA patients induces a characteristic arthritis in immunodeficient (SCID) mice.

The objective of this work was to study in more detail the human/murine SCID arthritis model with special emphasis on characteristic features initiated by rheumatoid arthritis (RA) synovial membrane (SM) as compared to appropriate control tissues. Small tissue samples from RA-SM, healthy lymph node, healthy SM, and granulomatous tissue of human origin were implanted into the left knee joint of mice with severe combined immunodeficiency (SCID), and the joints were analysed histologically after 7 days. In addition, a time course study, including non-invasive monitoring by serological parameters (human IgM, IgG, and IL-6) and Tc-99m-scintigraphy, was performed for up to 4 weeks on RA-SM recipients. All tissue implants induced transient exudative joint inflammation while RA-SM initiated a characteristic arthritis with pannus tissue of high cellular density, erosion, multinuclear giant cells, lining cell hyperplasia, fibroblast-like cell layers, chondroideal metaplasia, and fibrin deposits. Significantly elevated levels of human immunoglobulin and characteristic signs of chronic inflammation persisted for more than 4 weeks. We conclude that the hu/mu SCID arthritis with RA-SM implants comprises features of non-specific inflammation which is also transiently seen with control tissues but develops characteristic features of chronic RA-like synovitis thereafter.

Animals↗

Long-term management of acute respiratory failure in metabolic myopathy.

OBJECTIVE: To describe how patients cope with the proposal of treatment with intermittent artificial ventilation after acute respiratory failure due to progressive respiratory muscle weakness. DESIGN: Case series, follow-up study. SETTING: Neurological intensive care unit (ICU). PATIENTS: 7 consecutive patients with metabolic myopathy treated for acute respiratory failure between 1983 and 1992. INTERVENTIONS: Intermittent positive pressure ventilation (IPPV) via tracheostomy. MEASUREMENTS AND RESULTS: Symptoms of chronic hypoventilation preceded acute respiratory failure for months. With one exception, patients were mainly disabled from respiratory muscle weakness and sleep-related breathing disorders. IPPV was recommended to prevent recurrent respiratory failure. Two of three patients who accepted home IPPV returned to full-time jobs. One patient, who decided against IPPV, died from CO2 narcosis several months after discharge. All patients adhered to the respiratory regimen once instituted. CONCLUSIONS: Acute respiratory failure in chronic myopathy is heralded by daytime drowsiness. IPPV, or at least regular monitoring of waking and sleeping partial pressure of carbon dioxide, is highly recommended even if weaning is successful. IPPV improved quality of life. The treatment strategy at discharge from the ICU should be optimal, as patients are reluctant to modify regimens.

Activities of Daily Living↗

[Acute reversible encephalopathy with brain edema and serial seizures in pseudohypoparathyroidism].

A 16 year old patient with the typical clinical signs of Albright's hereditary dystrophia developed series of epileptic seizures with loss of consciousness, tonic muscle contractions and bite of the tongue. After termination of the seizures there was coma without focal neurological signs. CT scan revealed diffuse brain edema. Electroencephalographic studies showed generalized slowing. In laboratory tests the only abnormalities were marked hypocalcemia (1.15 mmol/l) and hyperphosphatemia. Blood parathyroid hormone (PTH) was elevated. PTH-Test confirmed the diagnosis of pseudohypoparathyroidism. The patient was treated with calcium and 1,25-dihydroxy-cholecalciferol. After few days the severe encephalopathy, CT and electroencephalographic changes were completely reversible. Hereditary disturbances of the parathyroid hormone metabolism are rare diseases. Hypocalcemia must be included into the differential diagnosis of seizures and brain edema to avoid invasive diagnostic and irrational treatment.

Adolescent↗

EU experimental study on wild boar trichinellosis.

From January 1994 onwards the Council Directive 92/45 EEC concerning the examination of wild game meat for trichinellosis is valid. Laboratory methods required are identical to those used for the examination of pork. In an international experiment the suitability of these methods to control wild boar meat was tested. Required meat parts of experimentally with T. spiralis infected wild boars were shipped to seven laboratories in Europe under code. It was concluded that trichinoscopy and pool sample digestion methods meant for pork examination could equally well be used for control of wild boar meat. The so called Trichomatic method required a few adaptations. Moreover it was demonstrated that extra washing procedures were required to prevent cross contamination between samples with Trichomatic equipment.

Animals↗

[How reliably does electromyography differentiate myopathies and neurogenic diseases?].

Electromyography is an essential part of neuromuscular diagnosis. Due to practicability, it mostly relies on qualitative judgement. Therefore, it is examiner dependent, and critical assessment of the EMG report is crucial. This may be furthered by (1) acquaintance with the genesis of the EMG, which has recently been rendered more transparent by computer simulation, and (2) experience with examiner-independent, quantitative diagnostic algorithms. By both approaches, it is intended to familiarize the reader with modern quality standards of EMG diagnosis. The diagnostic algorithm used to this end is discriminant MUP classification, which separated neurogenic and myopathic conditions without recourse to examiner judgements. This success shows that quantitative EMG, which has become available for routine practice, will add weight to EMG differential diagnosis.

Adult↗

Discriminant classification of motor unit potentials (MUPs) successfully separates neurogenic and myopathic conditions. A comparison of multi- and univariate diagnostical algorithms for MUP analysis.

Multivariate statistical methods may be more appropriate for the multidimensional material of quantitative motor unit potential (MUP) analysis than the multiple univariate tests of the conventional Buchthal analysis. Buchthal analysis was slightly modified before it was used as the gold standard for new multivariate diagnostical algorithms, based on principal component analysis and on MUP discriminant classification: muscle means of continuous variables were related to tolerance limits after adequate transformation. Chi-square tests were used for dichotomized variables, e.g., polyphasia. Sensitivity and specificity of the uni- and multivariate algorithms were compared for 539 muscles from patients with motor neuron diseases, neuropathies and myopathies and for 91 biceps brachii, rectus femoris and tibialis anterior control muscles. False positive results accumulated less than expected by repeat univariate tests for single MUP parameters, due to high correlation. Combination of single parameters to factor scores did not improve specificity. One advantage of factor analysis was that factor matrix and factor scores matched those of previous studies in spite of different input parameters, which may facilitate multicenter comparisons. Discriminant classification successfully separated neurogenic and myopathic conditions, even in myositic muscles and motor neuron diseases, where myopathic and neuropathic MUPs frequently intermingle. Discriminant classification may support expert decisions and add weight to EMG differential diagnosis.

Adult↗

Glycosylation of two recombinant human uterine tissue plasminogen activator variants carrying an additional N-glycosylation site in the epidermal-growth-factor-like domain.

Recombinant human uterine tissue plasminogen activator (tPA) glycosylation mutants carrying an additional N-glycosylation site in the epidermal-growth-factor-like domain due to the replacement of either Tyr67 by Asn (YN-tPA) or Gly60 by Ser (GS-tPA) were expressed in mouse epithelial cells (C127) in the presence of [6-3H]glucosamine. Glycopeptides comprising individual glycosylation sites were isolated and oligosaccharides attached were liberated by treatment with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols obtained after reduction were either directly characterized by high-pH anion-exchange chromatography (high-mannose and hybrid-type glycans) or preparatively subfractionated after enzymic desialylation and separation from sulphated asialooligosaccharides (complex-type sugar chains). Individual (sub)fractions of glucans were studied by methylation analysis, liquid secondary-ion mass spectrometry and, in part, by exoglycosidase digestion, whereas corresponding deglycosylated peptides were identified by amino acid analysis and N-terminal amino acid sequencing. The results revealed that Asn117 of YN-tPA carried exclusively high-mannose-type glycans with five to nine mannose residues similar to wild-type tPA expressed in this cell line [Pfeiffer, G., Schmidt, M., Strube, K.-H. & Geyer, R. (1989) Eur. J. Biochem. 186, 273-286]. In contrast, Asn117 of GS-tPA carried only small amounts (about 25%) of high-mannose and hybrid-type species and predominantly complex-type sugar chains (about 75%) which were partially incomplete and mostly devoid of fucose. Newly introduced N-glycosylation sites at Asn67 (YN-tPA) or Asn58 (GS-tPA) as well as those at Asn184 and Asn448 were solely substituted by complex-type glycans. Each carbohydrate attachment site displayed a peculiar oligosaccharide pattern with regard to branching and substitution by Gal alpha 3-residues, sulphate groups, intersecting GlcNAc and lactosamine repeats. Our study clearly demonstrates that creation of a new glycosylation site at Asn58 influenced the oligosaccharide processing and, hence, the glycosylation pattern at Asn117, whereas introduction of a new site at Asn67 did not. The relative amounts of complex-type glycans at Asn117 of GS-tPA correlated with the degree of carbohydrate substitution of Asn58. Therefore, it can be concluded that the presence of a sugar chain at the position and not the Gly to Ser mutation itself is responsible for the observed alteration of GS-tPA glycosylation.

Amino Acid Sequence↗

Tissue depth to lung for electron beam boost therapy of the breast.

Radiation therapy of the breast frequently employs electron beam boost therapy of the tumor bed. The electron energy is typically chosen based on the location of the tumor and tissue depth to lung within the electron field. This paper proposes a simple technique to estimate the tissue depth to lung using a port film taken orthogonal to the electron beam axis and patient axis for arbitrary electron beam gantry angles and patient table angles. The port film is taken with the patient in standard position (table angle of 0 degrees) and the gantry at right angles to the electron field axis, clearly showing the depth to lung. The mathematical solution for arbitrary electron field gantry angle and patient table angle is presented.

Breast↗

Glycosylation of the thrombin-like serine protease ancrod from Agkistrodon rhodostoma venom. Oligosaccharide substitution pattern at each N-glycosylation site.

In a previous study, we determined the structures of the glycans present in ancrod, a thrombin-like serine protease from the venom of the Malayan pit viper Agkistrodon rhodostoma (Pfeiffer et al. (1992) Eur J Biochem 205:961-78). In order to allocate the various carbohydrate chains to distinct N-glycosylation sites of the molecule, we have now isolated individual glycopeptides. Peptide moieties were identified after deglycosylation with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F by amino acid analysis and sequencing. Liberated oligosaccharides were assigned to the previously deduced carbohydrate structures by high performance liquid chromatography. Although only quantitative differences were observed, the results indicate that each glycosylation site of ancrod carries its characteristic oligosaccharide pattern. Furthermore, all potential sites were shown to be substituted by carbohydrates.

Agkistrodon↗

Frequency analysis and duration of motor unit potentials: reliability and diagnostic usefulness.

We studied the correlation, reliability and diagnostic usefulness of different time and frequency parameters of motor unit potentials (MUPs). Most frequency parameters were redundant because of high correlation with conventional MUP parameters. Variable selection algorithms for discriminant analysis indicated that center frequency (CENTFR) and spike duration (SPD) improved the discrimination between MUPs from normal, myopathic and neuropathic muscles. This was corroborated by univariate statistical tests comparing mean MUP duration (DUR), mean CENTFR and mean SPD of pathological muscles with those of normal muscles. One-sided tests for increased mean SPD improved the sensitivity for neurogenic changes and one-sided tests for reduced mean CENTFR improved the sensitivity for myopathic changes. The rate of false positive results did not increase by these additional tests. The retest reliability of CENTFR was superior to that of DUR. CENTFR and SPD are recommendable new parameters for quantitative MUP analysis based either on multi- or univariate statistics.

Action Potentials↗

Biosynthesis of sulfated glycoprotein-N-glycans present in recombinant human tissue plasminogen activator.

Recombinant human tissue plasminogen activator expressed in murine epithelial cells carries, in part, sulfated N-glycans, which are characterized by the presence of a NeuAc alpha 3[SO4-6]Gal unit. In order to study the biosynthesis of this novel structural element, corresponding sulfated asialooligosaccharide alditols were resialylated in vitro using a crude sialyltransferase preparation from murine liver which was shown to contain Gal beta 1,3(4)GlcNAc alpha 2,3-sialyltransferase activity. Products were analyzed for transfer of sialic acid residues by anion-exchange HPLC. The results demonstrated that resialylation of SO4-6Gal-residues did not occur. Therefore, it may be concluded that transfer of the sulfate group is the final step in the biosynthesis of this structural epitope.

Animals↗

Carbohydrate structure of a thrombin-like serine protease from Agkistrodon rhodostoma. Structure elucidation of oligosaccharides by methylation analysis, liquid secondary-ion mass spectrometry and proton magnetic resonance.

The carbohydrate side chains of the thrombin-like serine protease ancrod from the venom of the Malayan pit viper Agkistrodon rhodostoma were liberated from tryptic glycopeptides by treatment with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F and fractionated by high-performance liquid chromatography. Glycans obtained were characterized by digestion with exoglycosidases, methylation analysis and, in part, by liquid secondary-ion mass spectrometry and 1H-NMR spectroscopy. The results reveal that this snake venom glycoprotein contains partially truncated di-, tri- and tetraantennary complex type N-glycans carrying Fuc(alpha 1-6) residues at the innermost N-acetylglucosamine and solely (alpha 2-3)-linked sialic acid substituents. As a characteristic feature, ancrod oligosaccharides comprise mainly sialylated Gal beta 3GlcNAc beta lactosamine antennae. Furthermore, a small proportion of the sugar chains were found to carry a NeuAc alpha 3GalNAc beta 4GlcNAc beta antenna exclusively linked to C-2 of Man(alpha 1-3) residues of the pentasaccharide core. Thus, many of the glycans found represent novel glycoprotein-N-glycan structures.

Carbohydrate Sequence↗

Turn and phase counts of individual motor unit potentials: correlation and reliability.

Different turn algorithms are used for quantitative motor unit potential (MUP) analysis. To compare their retest reliability, 420 myopathic and neuropathic MUPs were recorded twice and the turn count of the first registration was correlated with that of the second. Reliability was best for the algorithm according to Willison as compared to the conventionally used algorithms based on amplitude criteria for 2 or 3 successive relative extrema. As demonstrated by discriminant analysis, an amplitude limit of 25 microV yielded more useful turn counts than a limit of 50 microV if myopathic MUPs had to be discriminated from normal MUPs. For this discrimination the turn count was superior to the phase count which did not further improve the discriminant model. This was different for the discrimination between normal and neuropathic MUPs. In this case, both parameters measured partly independent features of the MUP and had to be considered together.

Adult↗