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Biomedical subjects

A Gottschalk

Publications and source records attributed to A Gottschalk.

At least 19 recordsLinked to original sources

[Rupture of the trachea after emergency endotracheal intubation].

The rupture of the trachea is a rare but serious complication after endotracheal intubation. We report the case of a 77-year-old severely diseased woman with emergency intubation after development of acute respiratory distress. Four days after the emergency intubation a laceration of the membraneous part of the trachea was diagnosed. The patients general condition and the infaust prognosis resulted in the lack of therapeutic options and the death of the patient. According to the forensic autopsy the secondary perforation is probably a consequence of intubation or a pressure lesion of the tube in combination with a weakness of the membraneous part of the trachea due to impaired microperfusion. Every physician performing an intubation has to be aware of the risk and the consequences of a tracheal rupture.

Aged↗

[Topography of the inferior alveolar nerve in relation to cystic processes of the mandible in dental MRI].

PURPOSE: Cystic processes are changing the course of the inferior alveolar nerve in the mandible. This study evaluates the possibility of demonstrating the relationship between space-occupying processes and the course of the neurovascular bundle. MATERIALS AND METHODS: Thirteen patients with cystic processes in the mandible (9 keratocystic lesions, 1 eosinophilic granuloma, 1 plasmocytoma, 2 adamantinomas) were examined by MRI (1.5-T magnet, 8-cm surface coil, PD-gradient-echo-sequences in sagittal and coronal orientation, without enhancement) and the results retrospectively evaluated. RESULTS: The entire course of the nerve could be delineated in all patients. In six patients with minor cystic processes, the nerve was identified in both sagittal and coronal orientation. In seven patients with major cystic lesions, only parts of the nerve were detected in either image orientation, but the nerve could be visualized in its entire length by evaluating coronal and sagittal images side by side. CONCLUSION: It is possible to delineate the inferior alveolar nerve in its entirety along pathologic mandibular lesions. For large cystic lesions, this requires the evaluation of both coronal and sagittal sections of multidirectional MRI.

Adolescent↗

Bell's palsy: what is the prognostic value of measurements of signal intensity increases with contrast enhancement on MRI?

Our objective was to assess the prognostic value of measurements of the degree of contrast enhancement of the intratemporal segments of the facial nerve. We prospectively obtained MRI, slice thickness <1 mm of 20 patients with a facial palsy on the first day of inpatient treatment, and measured contrast enhancement of the nerve. The data were compared with compound muscle action potential (CMAP) measurements and the clinical course. Analysis of the initial enabled differentiation of three patients whose palsy was to show no improvement from 17 whose palsy was to resolve as expected. No patient with a poor outcome showed lesser increase in signal in the internal auditory canal, pars tympanica and pars mastoidea than patients who fully recovered. In no patient who had been diagnosed on the basis of the initial MRI as having a "normal" palsy was the amplitude of the (CMAP) reduced to less than 20% that of the normal side. Measurement of contrast enhancement was thus shown to be a prognostic indicator and may provide a basis for a differential treatment of facial palsy.

Adolescent↗

[Analgosedation, analgesia with remifentanil in incontinence surgery via tension-free vaginal tape].

OBJECTIVE: The tension-free vaginal tape operation (TVT) is a new surgical treatment of stress urinary incontinence in women. The tape has to be placed at the level of midurethra in the left and right paraurethral canal and has to be brought up to the abdominal wall in close contact with the back of the pubic bone with a special needle instrument. The performed anesthesia is decisive for the operative success, because a sufficient analgesia is demanded and, on the other hand, the correct placement and tension of the urethral tape has to be controlled by the patient performing a stress test by coughing and pressing. In this context the opioid remifentanil seems to be specially suitable because of its pharmacologic characteristics. METHODS: In this retrospective analysis the anesthesia related data of a total of 70 patients undergoing TVT surgery with remifentanil analgesia within one year were reviewed according to their anesthesia protocols. RESULTS: All patients underwent remifentanil analgesia in combination with local anesthesia. In no case the performed procedure had to be changed. In 7 cases a temporary decrease of the pulsoximetrically measured oxygen saturation to less-than-or-equal 92 % occurred, which could be treated by reduction of the infusion rate of remifentanil or by assisted ventilation. All patients were adequately able to perform the intraoperatively required stress test. 16 patients suffered from nausea and/or vomiting postoperatively. CONCLUSION: Continuous infusion of remifentanil is suitable for the short time profound analgesia needed for the TVT operation because of the pharmacologic characteristics of remifentanil. A antiemetic prophylaxis should be performed with this analgetic regime.

Aged↗

[The prognostic value of quantified MRI at an early stage of Bell's palsy].

OBJECTIVE: The aim of the study was to assess whether MRI has a prognostic value at an early stage of Bell's palsy. MATERIAL AND METHODS: Prospective, blinded study on 30 patients suffering from Bell's palsy, who came to hospital until the sixth day of illness, to receive high doses steroid therapy. MRI was done on the first day of inpatient treatment as a gradient-echo-sequence with a slice thickness of 0.7 mm before and after i. v. administration of 0.1 mmol GdDTPA/kg weight. The signal intensity increase was evaluated quantitatively by region on interest (ROI). The results were compared to the clinical outcome and the results of electrophysiology. RESULTS: The examinations of all patients could be evaluated. The 3 patients who developed a chronic facial paralysis were detected by MRI on the first day of inpatient treatment. The patients, who showed MR signs for an unfavorable course, had a highly significant pathologic compound muscle action potential (CMAP) as a result of the electrophysiologic measurement. Rather than using complex measurement procedures it is possible to obtain reliable prognostic information from just one measurement within the Internal auditory canal before and after i. v. administration of contrast. CONCLUSION: MRI has a prognostic value at an early stage of the illness. In the clinical setting this measurement is easy to perform, so that it is possible to obtain prognostic information at a stage when causal treatment is still possible.

Action Potentials↗

New concepts in acute pain therapy: preemptive analgesia.

Pain, which is often inadequately treated, accompanies the more than 23 million surgical procedures performed each year and may persist long after tissue heals. Preemptive analgesia, an evolving clinical concept, involves the introduction of an analgesic regimen before the onset of noxious stimuli, with the goal of preventing sensitization of the nervous system to subsequent stimuli that could amplify pain. Surgery offers the most promising setting for preemptive analgesia because the timing of noxious stimuli is known. When adequate drug doses are administered to appropriately selected patients before surgery, intravenous opiates, local anesthetic infiltration, nerve block, subarachnoid block and epidural block offer benefits that can be observed as long as one year after surgery. The most effective preemptive analgesic regimens are those that are capable of limiting sensitization of the nervous system throughout the entire perioperative period.

Acute Disease↗

[Ropivacaine 0.2% versus bupivacaine 0.125% plus sufentanil for continuous peridural analgesia following extended abdominal operations].

OBJECTIVE: An improved opioid-free analgesia concept using thoracic epidural anlgesia with a low concentrated local anaesthetic alone could be of practical interest for hospitals which are unable to guarantee continuous monitoring on the wards. METHODS: We have compared in a prospective, randomized, double-blind study, the analgesic effects and side effects of ropivacaine 0.2% (Group 1) with bupivacaine 0.125% plus 0.5 microgram ml-1 sufentanil (Group 2) via a thoracic epidural catheter during the first 24 hours after major abdominal surgery in 28 gynaecological tumour patients. Assessments were performed 8, 12, 16, 20 and 24 hours after surgery. RESULTS: No differences were seen in duration of surgery, intraoperative opioid and supplemental analgesic requirements. As a main result VAS values for pain during mobilisation were higher in Group 1 when compared with Group 2 (p < 0.01) after 20 and 24 hours of continuous epidural infusion (10 ml h-1) whereas VAS values at rest were comparable (p < 0.1) at all measurepoints. Intensity of motor block and side effects did not differ between groups. CONCLUSION: The present study shows that continuous epidural infusion of 0.2% ropivacaine alone provides comparable analgesia at rest, but less profound pain relief during mobilisation within the first 24 hours after major abdominal surgery than bupivacaine 0.125% with sufentanil.

Abdomen↗

Amantadine, a N-methyl-D-aspartate receptor antagonist, does not enhance postoperative analgesia in women undergoing abdominal hysterectomy.

UNLABELLED: N-methyl-D-aspartate (NMDA) antagonists administered before surgery will improve postoperative analgesia, presumably by inhibiting spinal sensitization processes. However, current clinical formulations of NMDA antagonists either enable only an oral application (i.e., dextromethorphan) or are associated with psychotropic side effects, as with the IV delivery of ketamine. Because of its noncompetitive NMDA receptor antagonist characteristics, amantadine may improve postoperative analgesia when administered before surgically induced trauma. In this prospective, randomized clinical study, we examined whether female patients undergoing elective abdominal hysterectomy experienced less postoperative pain when IV amantadine was applied in comparison with placebo before the start of surgery. Thirty patients were randomly assigned to receive 500 mL saline IV before the induction of standardized general anesthesia in Group 1 (Control group) or, in a double-blinded manner, 200 mg amantadine IV in 500 mL saline in Group 2 (Treatment group). Postoperative pain control was provided via IV patient-controlled analgesia with piritramide. During the first 48 h after tracheal extubation, pain perception was assessed by visual analog scales, and all analgesic requirements were documented. There were no significant differences between the two groups with respect to pain scores, postoperative analgesic requirements, and the incidence of side effects. Because of no differences in postoperative pain or opioid consumption, we conclude that a preoperative dose of 200 mg amantadine IV fails to enhance postoperative analgesia in patients undergoing elective abdominal hysterectomy. IMPLICATIONS: Because of no differences in postoperative pain or opioid consumption, we conclude that a preoperative dose of 200 mg amantadine IV fails to enhance postoperative analgesia in patients undergoing elective abdominal hysterectomy.

Aged↗

A novel yeast U2 snRNP protein, Snu17p, is required for the first catalytic step of splicing and for progression of spliceosome assembly.

We have isolated and microsequenced Snu17p, a novel yeast protein with a predicted molecular mass of 17 kDa that contains an RNA recognition motif. We demonstrate that Snu17p binds specifically to the U2 small nuclear ribonucleoprotein (snRNP) and that it is part of the spliceosome, since the pre-mRNA and the lariat-exon 2 are specifically coprecipitated with Snu17p. Although the SNU17 gene is not essential, its knockout leads to a slow-growth phenotype and to a pre-mRNA splicing defect in vivo. In addition, the first step of splicing is dramatically decreased in extracts prepared from the snu17 deletion (snu17Delta) mutant. This defect is efficiently reversed by the addition of recombinant Snu17p. To investigate the step of spliceosome assembly at which Snu17p acts, we have used nondenaturing gel electrophoresis. In Snu17p-deficient extracts, the spliceosome runs as a single slowly migrating complex. In wild-type extracts, usually at least two distinct complexes are observed: the prespliceosome, or B complex, containing the U2 but not the U1 snRNP, and the catalytically active spliceosome, or A complex, containing the U2, U6, and U5 snRNPs. Northern blot analysis and affinity purification of the snu17Delta spliceosome showed that it contains the U1, U2, U6, U5, and U4 snRNPs. The unexpected stabilization of the U1 snRNP and the lack of dissociation of the U4 snRNP suggest that loss of Snu17p inhibits the progression of spliceosome assembly prior to U1 snRNP release and after [U4/U6.U5] tri-snRNP addition.

Amino Acid Sequence↗

Chronic alcohol consumption and cerebral indices of oxidative stress: is there a link?

BACKGROUND: It is still difficult to define the biochemical mechanisms that cause alterations in neuronal function and plasticity and neuronal cell loss in the brains of alcohol-dependent patients. METHODS: To evaluate the extent of cerebral alcohol-induced oxidative stress ex vivo, we investigated the levels of glutathione (GSH), its oxidation product glutathione disulfide (GSSG, produced by GSH-peroxidases), and the activities of catalase and superoxide dismutases (SOD). In addition, selected brain regions from up to 22 subjects (versus controls) were studied post mortem to compare the amount of oxidized DNA-base 8-hydroxy-2'-deoxyguanosine (8-OHdG) with levels of deoxyguanosine (dG) in mitochondrial and nuclear DNA. RESULTS: The most prominent findings showed significantly decreased GSH/(GSH+2GSSG) molar redox (oxidation-reduction) ratios in the corpus mamillare and cerebellum, which appeared due to an increase in GSSG caused by chronic alcohol intake. Catalase activity was increased in only the frontal cortex, whereas decreased catalase activity was found in the corpus callosum. In contrast, neither copper-zinc-superoxide dismutase (CuZnSOD) and manganese-superoxide dismutase (MnSOD) activities nor 8-OHdG/dG molar ratios were altered, although a tendency toward higher OHdG/dG ratios in temporal and parietal cortex from alcohol-dependent patients could be detected when mitochondrial DNA was analyzed selectively. CONCLUSIONS: We propose that decreased brain GSH/(GSH+2GSSG) molar redox (oxidation-reduction) ratios in alcohol-dependent patients may reflect neural impairment due to increased peroxide production after chronic alcohol consumption. However, future experiments, investigating the activities of enzymes and cofactors involved in GSH synthesis and metabolism in the human brain, will have to validate the specificity of these results for oxidative stress.

8-Hydroxy-2'-Deoxyguanosine↗

The yeast U5 snRNP coisolated with the U1 snRNP has an unexpected protein composition and includes the splicing factor Aar2p.

We describe the purification and characterization of a 16S U5 snRNP from the yeast Saccharomyces cerevisiae and the identification of its proteins. In contrast to the human 20S U5 snRNP, it has a comparatively simple protein composition. In addition to the Sm core proteins, it contains only two of the U5 snRNP specific proteins, Prp8p and Snu114p. Interestingly, the 16S U5 snRNP contains also Aar2p, a protein that was previously implicated in splicing of the two introns of the MATa1 pre-mRNA. Here, we demonstrate that Aar2p is essential and required for in vivo splicing of U3 precursors. However, it is not required for splicing in vitro. Aar2p is associated exclusively with this simple form of the U5 snRNP (Aar2-U5), but not with the [U4/U6.U5] tri-snRNP or spliceosomal complexes. Consistent with this, we show that depletion of Aar2p interferes with later rounds of splicing, suggesting that it has an effect when splicing depends on snRNP recycling. Remarkably, the Aar2-U5 snRNP is invariably coisolated with the U1 snRNP regardless of the purification protocol used. This is consistent with the previously suggested cooperation between the U1 and U5 snRNPs prior to the catalytic steps of splicing. Electron microscopy of the Aar2-U5 snRNP revealed that, despite the comparatively simple protein composition, the yeast Aar2-U5 snRNP appears structurally similar to the human 20S U5 snRNP. Thus, the basic structural scaffold of the Aar2-U5 snRNP seems to be essentially determined by Prp8p, Snu114p, and the Sm proteins.

Fungal Proteins↗

Low-molecular-weight heparin vs heparin in the treatment of patients with pulmonary embolism. American-Canadian Thrombosis Study Group.

BACKGROUND: Pulmonary embolism (PE) occurs in 50% or more of patients with proximal deep-vein thrombosis. Low-molecular-weight heparin treatment is effective and safe in patients with deep vein thrombosis and may also be so in patients with PE. Recent rigorous clinical trials have established objective criteria for determining a high probability of PE by perfusion lung scanning. OBJECTIVE: To compare low-molecular-weight heparin with intravenous heparin for the treatment of patients with objectively documented PE and underlying proximal deep vein thrombosis. METHODS: In a multicenter, double-blind, randomized trial, we compared fixed-dose subcutaneous low-molecular-weight heparin (tinzaparin sodium) given once daily with dose-adjusted intravenous heparin given by continuous infusion using objective documentation of clinical outcomes. Pulmonary embolism at study entry was documented by the presence of high-probability lung scan findings. RESULTS: Of 200 patients with high-probability lung scan findings at study entry, none of the 97 who received low-molecular-weight heparin had new episodes of venous thromboembolism compared with 7 (6.8%) of 103 patients who received intravenous heparin (95% confidence interval for the difference, 1.9%-11.7%; P = .01). Major bleeding associated with initial therapy occurred in 1 patient (1.0%) who was given low-molecular-weight heparin and in 2 patients (1.9%) given intravenous heparin (95% confidence interval for the difference, -2.4% to 4.3%). CONCLUSIONS: Low-molecular-weight heparin administered once daily subcutaneously was no less effective and probably more effective than use of dose-adjusted intravenous unfractionated heparin for preventing recurrent venous thromboembolism in patients with PE and associated proximal deep vein thrombosis. Our findings extend the use of low-molecular-weight heparin without anticoagulant monitoring to patients with submassive PE.

Adolescent↗

Identification by mass spectrometry and functional analysis of novel proteins of the yeast [U4/U6.U5] tri-snRNP.

The 25S [U4/U6.U5] tri-snRNP (small nuclear ribonucleoprotein) is a central unit of the nuclear pre-mRNA splicing machinery. The U4, U5 and U6 snRNAs undergo numerous rearrangements in the spliceosome, and knowledge of all of the tri-snRNP proteins is crucial to the detailed investigation of the RNA dynamics during the spliceosomal cycle. Here we characterize by mass spectrometric methods the proteins of the purified [U4/U6.U5] tri-snRNP from the yeast Saccharomyces cerevisiae. In addition to the known tri-snRNP proteins (only one, Lsm3p, eluded detection), we identified eight previously uncharacterized proteins. These include four Sm-like proteins (Lsm2p, Lsm5p, Lsm6p and Lsm7p) and four specific proteins named Snu13p, Dib1p, Snu23p and Snu66p. Snu13p comprises a putative RNA-binding domain. Interestingly, the Schizosaccharomyces pombe orthologue of Dib1p, Dim1p, was previously assigned a role in cell cycle progression. The role of Snu23p, Snu66p and, additionally, Spp381p in pre-mRNA splicing was investigated in vitro and/or in vivo. Finally, we show that both tri-snRNPs and the U2 snRNP are co-precipitated with protein A-tagged versions of Snu23p, Snu66p and Spp381p from extracts fractionated by glycerol gradient centrifugation. This suggests that these proteins, at least in part, are also present in a [U2.U4/U6.U5] tetra-snRNP complex.

Fungal Proteins↗

Mapping of secondary somatosensory cortex activation induced by vibrational stimulation: an fMRI study.

Sensory functional MRI was performed in seven normal volunteers at 1. 5 T using a vibratory stimulus applied to the pad of the first finger of the left hand. The data was normalized to a standard atlas, and individual and group statistical parametric maps were computed. Robust bilateral activation was demonstrated in the secondary somatosensory cortex (SII), indicating a bilateral representation of SII in humans. Greater maxima and activation volumes were achieved in contralateral SII as compared to SI. Sensory fMRI can provide a sensitive assay for probing the nature and function of SII in vivo.

Adult↗

Interaction of the U1 snRNP with nonconserved intronic sequences affects 5' splice site selection.

Intron definition and splice site selection occur at an early stage during assembly of the spliceosome, the complex mediating pre-mRNA splicing. Association of U1 snRNP with the pre-mRNA is required for these early steps. We report here that the yeast U1 snRNP-specific protein Nam8p is a component of the commitment complexes, the first stable complexes assembled on pre-mRNA. In vitro and in vivo, Nam8p becomes indispensable for efficient 5' splice site recognition when this process is impaired as a result of the presence of noncanonical 5' splice sites or the absence of a cap structure. Nam8p stabilizes commitment complexes in the latter conditions. Consistent with this, Nam8p interacts with the pre-mRNA downstream of the 5' splice site, in a region of nonconserved sequence. Substitutions in this region affect splicing efficiency and alternative splice site choice in a Nam8p-dependent manner. Therefore, Nam8p is involved in a novel mechanism by which a snRNP component can affect splice site choice and regulate intron removal through its interaction with a nonconserved sequence. This supports a model where early 5' splice recognition results from a network of interactions established by the splicing machinery with various regions of the pre-mRNA.

5' Untranslated Regions↗