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Biomedical subjects

M Rasmussen

Publications and source records attributed to M Rasmussen.

At least 37 records · Page 2Linked to original sources

Are cells rescued from 'low density death' by co-operation between phospholipases C AND D?

Cells of the ciliate Tetrahymena thermophila die when transferred at low density to a lipid-free nutritionally complete medium. This death is prevented and they will start to proliferate if protein kinase C is activated and this activation is sustained. We propose that this takes place in two stages. Firstly, the phospholipase C pathway beginning with and specific for phosphatidylinositol leads to the formation of diacylglycerol and inositol tris -phosphate. Diacylglycerol activates protein kinase C, and inositol tris -phosphate via Ca(2+)phospholipase D (PLD). Secondly, the protein kinase C response can now be sustained by diacylglycerol produced by phospholipase D, using phosphatidylcholine and phosphatidylserine as substrates. Should this switching from PI-specific phospholipase C (PLC) to phospholipase D fail, then the cell will die in the course of milliseconds during the minutes following inoculation.

Animals↗

Virtual temporal bone: creation and application of a new computer-based teaching tool.

The human temporal bone is a 3-dimensionally complex anatomic region with many unique qualities that make anatomic teaching and learning difficult. Current teaching tools have proved only partially adequate for the needs of the aspiring otologic surgeon in learning this anatomy. We used a variety of computerized image processing and reconstruction techniques to reconstruct an anatomically accurate 3-dimensional computer model of the human temporal bone from serial histologic sections. The model is viewed with a specialized visualization system that allows it to be manipulated easily in a stereoscopic virtual environment. The model may then be interactively studied from any viewpoint, greatly simplifying the task of conceptualizing and learning this anatomy. The system also provides for simultaneous computer networking that can bring distant participants into a single shared virtual teaching environment. Future directions of the project are discussed.

Computer Simulation↗

High-dose rectal and oral acetaminophen in postoperative patients--serum and saliva concentrations.

BACKGROUND: The primary purpose of the study was to examine the absorption of acetaminophen by measuring serum and saliva concentrations produced by a standard postoperative acetaminophen dosing regimen and secondary to examine the correlation between saliva and serum concentrations of acetaminophen after rectal and oral dosing. METHODS: Twenty-four women, aged 18-60 years, scheduled for minor gynaecological laparoscopic surgery were studied. Patients received acetaminophen 2000 mg suppositories after surgery and oral doses of 1000 mg at 4 and 8 h postoperatively. Alfentanil was available via patient-controlled analgesia. Saliva and blood samples were collected postoperatively. RESULTS: At 1, 2, 3, and 4 h after rectal dosing the saliva concentrations (mean+/-SD) were 15.2+/-5.9 micromol/l, 33.7+/-12.5 micromol/l, 45.5+/-19.1 micromol/l, and 55.4+/-23.1 micromol/l, respectively. The serum concentrations at 2 and 4 h were 31.0+/-11.2 micromol/l and 54.8+/-23.8 micromol/l, respectively. Additional oral dosing resulted in saliva concentrations at 5, 8, and 9 h of 99.7+/-49.5 micromol/l, 106.9+/-31.7 micromol/l, and 139.3+/-55.4 micromol/l, respectively, with coincident serum concentrations of 100.1 +/- 50.2 micromol/l, 105.6+/-29.0 micromol/l, and 141.2+/-52.1 micromol/l. After rectal dosing the linear regression resulted in r2=0.96, P<0.001 and saliva/ serum-ratio=0.99. After additional oral dosing the outcome of linear regression was: r2=0.90, P<0.001 and saliva/serum-ratio= 1.00. CONCLUSION: The slow and ongoing absorption process resulting in no maximum concentration within 4 h after administration of 2000 mg acetaminophen suppositories makes this rectal regimen therapeutically irrational for treatment of postoperative pain. The significant ratio and linear correlation between saliva and serum concentrations of acetaminophen suggests that saliva could be used instead of blood to monitor acetaminophen administration in patients.

Absorption↗

Tropisetron reduces postoperative vomiting in children undergoing tonsillectomy.

In this patient, parent and investigator blinded, randomized, placebo-controlled study, children undergoing tonsillectomy (mean age 6.4 years) received either intravenous placebo (n=36) or tropisetron 0.2 mg.kg-1 up to 5 mg (n=35) at induction of anaesthesia with halothane, nitrous oxide and oxygen. Morphine and paracetamol were given in theatre for postoperative pain. Episodes of vomiting were recorded during the first 24 h after surgery. Intravenous tropisetron was significantly (P<0.001, chi-squared) more effective than placebo in controlling the incidence and frequency of emesis during the first 24 h: vomiting was reduced from 89% to 46% and the mean number of vomits from 4.6 to 2.4. Minor side-effects occurred equally in both the placebo and active groups. Intravenous tropisetron is an effective and safe antiemetic for reducing postoperative vomiting in children undergoing tonsillectomy or adenotonsillectomy.

Anesthesia, Inhalation↗

Tropisetron plus dexamethasone is more effective than tropisetron alone for the prevention of postoperative nausea and vomiting in children undergoing tonsillectomy.

The 5-HT3 antagonists are effective in reducing postoperative nausea and vomiting (PONV) associated with paediatric tonsillectomy. Although prophylactic tropisetron can reduce the incidence of PONV by half, the resulting level of over 40% is still unacceptably high. The aim of this study was to evaluate the effect of adding dexamethasone to tropisetron. In a blinded study, 59 children (mean age 6.1 years) were administered 0.1 mg.kg-1 up to 2 mg of tropisetron and 66 children (mean age 5.7 years) received the same dose of tropisetron plus 0.5 mg.kg-1 up to 8 mg of dexamethasone. Both drugs were given intravenously during induction of anaesthesia for tonsillectomy. During the inpatient stay of 24 h, the incidence of postoperative vomiting in the tropisetron alone group was 53% compared with 26% in the combination group (P=0.002, chi-squared). A significant reduction in nausea from 53% to 30% was also observed (P=0.02). Parents completed a daily diary for 5 days following discharge. Delayed vomiting occurred in 27% and 11% of the tropisetron and combination therapy groups, respectively (P=0.025) Sixteen percent and 9%, respectively, required medical attention (P=0.27). Tropisetron plus dexamethasone is more effective than tropisetron alone in reducing the incidence of PONV following paediatric tonsillectomy.

Adolescent↗

Pharmacokinetics of rectal paracetamol after repeated dosing in children.

Twenty-three children (aged between 9 weeks and 11 yr) were given paracetamol suppositories 25 mg kg-1 every 6 h (maximum 5 days) after major surgery and serum and saliva concentrations were measured. There was a good correlation (r = 0.91, P < 0.05) between saliva and serum concentrations. A one-compartment linear model with first-order elimination and absorption and lag-time was fitted to the data (ADAPT II). At steady state, the mean (SD) concentration was 15.2 (6.8) mg litre-1. Mean (SD) time to reach 90% of the steady state concentration was 11.4 (8.6) h. Body weight, age and body surface area were well correlated (P < 0.05) with clearance and apparent volume of distribution. There was no evidence of accumulation leading to supratherapeutic concentrations during this dosing schedule for a mean of approximately 2-3 days.

Acetaminophen↗

Knowledge and attitudes about vaginal birth after Caesarean section in Australian hospitals. VBAC Study Group. Vaginal Birth After Caesarean.

A survey of staff attitudes and knowledge about vaginal birth after Caesarean section (VBAC) was undertaken in Australian hospitals. There was a high response rate (67%), and over 900 responses were analysed. Generally, there was a high level of awareness about outcomes and the relative importance of many issues in considering VBAC. Registrars, consultants and midwives differed significantly in some aspects of their knowledge and attitudes to VBAC. There was also a wide range of opinion within each group. Approximately half (53%) of respondents believed patients should be actively encouraged to consider VBAC, whereas 47% felt it should be simply presented as an option.

Attitude of Health Personnel↗

Vaginal birth after Caesarean section: an Australian multicentre study. VBAC Study Group.

Retrospective analysis of medical records and individual case review was undertaken at 11 major obstetric hospitals for a 5 year period from July 1992 to June 1997 to investigate rates of vaginal birth after Caesarean section (VBAC), the occurrences of uterine rupture, and the outcomes for mother and infant following rupture. Total deliveries were 234,015, of which 21,452 or 9.2% were associated with one or more previous Caesarean sections. Within this scar group, 5419 patients or 25.3% were delivered vaginally. There were 62 cases of significant uterine rupture with no maternal deaths. Perinatal mortality with rupture was 25% and serious maternal complications (usually hysterectomy) occurred in 25% of those with uterine rupture. In women attempting vaginal delivery after a previous lower segment Caesarean section, the uterine rupture rate was estimated at 0.3%, with 0.05% experiencing a perinatal death and 0.05% requiring a hysterectomy. Although VBAC rates in Australia remain lower than many overseas reported series, rates are increasing. While rupture continues to be associated with serious adverse outcomes, the incidence of rupture during trial of labour is low and appears to be associated with a better outcome than rupture of an unscarred uterus.

Australia↗

SclA, a novel collagen-like surface protein of Streptococcus pyogenes.

Surface proteins of Streptococcus pyogenes are important virulence factors. Here we describe a novel collagen-like surface protein, designated SclA (streptococcal collagen-like surface protein). The sclA gene was identified in silico using the Streptococcal Genome Sequencing Project with the recently identified protein GRAB as the probe. SclA has a signal sequence and a cell wall attachment region containing the prototypic LPXTGX motif. The surface-exposed part of SclA contains a unique NH(2)-terminal domain of 73 amino acids, followed by a collagen-like region. The sclA gene was found to be positively regulated by Mga, a transcriptional activator of several S. pyogenes virulence determinants. A mutant lacking cell wall-associated SclA was constructed and was found to be as effective as wild-type bacteria in platelet aggregation, survival in fresh human blood, and adherence to pharyngeal cells. The sclA gene was found in all 12 S. pyogenes strains that were investigated using PCR. Sequence analysis revealed that the signal sequence and the cell wall attachment region are highly conserved. The collagen-like domain is variable in its NH(2)-terminal region and has conserved repeated domains in its COOH-terminal part. SclA proteins from most strains have additional proline-rich repeats spacing the collagen-like domain and the cell wall attachment sequence. The unique NH(2)-terminal region is hypervariable, but computer predictions indicate a common secondary structure, with two alpha helices connected by a loop region. Immune selection may explain the hypervariability in the NH(2)-terminal region, whereas the preserved secondary structure implies that this region has a common function. These features and the Mga regulation are shared with the M protein of S. pyogenes. Moreover, as with the gene encoding the M protein, phylogenetic analysis indicates that horizontal gene transfer has contributed to the evolution of sclA.

Animals↗

Determinants of population changes in fibrinogen and factor VII over 6 years: the Atherosclerosis Risk in Communities (ARIC) Study.

Although numerous cross-sectional studies have identified possible determinants of plasma fibrinogen and factor VII levels, few prospective studies exist. We assessed the longitudinal relation of changes in fibrinogen and factor VII over 6 years with changes to other cardiovascular risk factors in a sample of 440 men and 549 women from the Atherosclerosis Risk in Communities (ARIC) study. Fibrinogen increased more in older participants, those with or who developed diabetes, those who at any time smoked, and those whose plasma HDL cholesterol or triglycerides decreased and increased less in female participants who started hormonal replacement therapy. Factor VII coagulant activity increased more in younger participants, women, those who gained greater weight or developed diabetes, those who quit smoking, those in whom plasma triglycerides decreased, and female participants who received hormonal replacement therapy. Thus, our longitudinal data suggest with some exceptions that adverse changes in cardiovascular risk factors are accompanied by increases in plasma levels of fibrinogen and factor VII.

Aging↗

Evidence that Alpers-Huttenlocher syndrome could be a mitochondrial disease.

We report an 11-year-old boy with a slight developmental delay and epilepsy. After he was placed on valproate, he developed hepatic failure and increasing neurologic symptoms, including epilepsia partialis continua, and died. Autopsy findings in liver and cerebrum were consistent with progressive neuronal degeneration of childhood with liver disease, also called Alpers-Huttenlocher syndrome. Ragged red fibers and cytochrome c oxidase negative fibers were present in muscle. These results suggest that Alpers-Huttenlocher syndrome, at least in some patients, is a mitochondrial disease.

Cerebral Cortex↗

The influence of the input function on quantitative rCBF by the Xe/CT method.

Measurements of rCBF by the Xe/CT method are based on the assumption of identity between the end-tidal xenon curve which is applied as input function, and the arterial xenon curve being the true input function to the brain. In this study corresponding end-tidal and arterial xenon curves were measured in an experimental animal model (part 1) and in 5 patients with traumatic brain injury (part 2) and used for rCBF calculation. In both studies rCBF was underestimated by using the end-tidal xenon concentration curve as brain input function. In part 1 rCBF underestimation was depended on pulmonary gas exchange; high or low levels of rCBF; tissue type; and xenon inhalation protocols. In part 2 the mean rCBF underestimation was 18.8 +/- 8.3%. In conclusion, non-invasive estimate of the input function should be considered as a source of error when defining quantitative blood flow values e.g. the flow thresholds of ischaemic infarction.

Animals↗

Radiological tele-immersion for next generation networks.

Since the acquisition of high-resolution three-dimensional patient images has become widespread, medical volumetric datasets (CT or MR) larger than 100 MB and encompassing more than 250 slices are common. It is important to make this patient-specific data quickly available and usable to many specialists at different geographical sites. Web-based systems have been developed to provide volume or surface rendering of medical data over networks with low fidelity, but these cannot adequately handle stereoscopic visualization or huge datasets. State-of-the-art virtual reality techniques and high speed networks have made it possible to create an environment for clinicians geographically distributed to immersively share these massive datasets in real-time. An object-oriented method for instantaneously importing medical volumetric data into Tele-Immersive environments has been developed at the Virtual Reality in Medicine Laboratory (VRMedLab) at the University of Illinois at Chicago (UIC). This networked-VR setup is based on LIMBO, an application framework or template that provides the basic capabilities of Tele-Immersion. We have developed a modular general purpose Tele-Immersion program that automatically combines 3D medical data with the methods for handling the data. For this purpose a DICOM loader for IRIS Performer has been developed. The loader was designed for SGI machines as a shared object, which is executed at LIMBO's runtime. The loader loads not only the selected DICOM dataset, but also methods for rendering, handling, and interacting with the data, bringing networked, real-time, stereoscopic interaction with radiological data to reality. Collaborative, interactive methods currently implemented in the loader include cutting planes and windowing. The Tele-Immersive environment has been tested on the UIC campus over an ATM network. We tested the environment with 3 nodes; one ImmersaDesk at the VRMedLab, one CAVE at the Electronic Visualization Laboratory (EVL) on east campus, and a CT scan machine in UIC Hospital. CT data was pulled directly from the scan machine to the Tele-Immersion server in our Laboratory, and then the data was synchronously distributed by our Onyx2 Rack server to all the VR setups. Instead of permitting medical volume visualization at one VR device, by combining teleconferencing, tele-presence, and virtual reality, the Tele-Immersive environment will enable geographically distributed clinicians to intuitively interact with the same medical volumetric models, point, gesture, converse, and see each other. This environment will bring together clinicians at different geographic locations to participate in Tele-Immersive consultation and collaboration.

Humans↗

Protein GRAB of streptococcus pyogenes regulates proteolysis at the bacterial surface by binding alpha2-macroglobulin.

In the molecular interplay between pathogenic microorganisms and their host, proteolytic mechanisms are believed to play a crucial role. Here we find that the important human pathogen Streptococcus pyogenes (group A Streptococcus) expresses a surface protein with high affinity (Ka = 2.0 x 10(8) M-1) for alpha2-macroglobulin (alpha2M), the dominating proteinase inhibitor of human plasma. The immunoglobulin-binding protein G of group C and G streptococci also contains an alpha2M-binding domain and a gene encoding protein GRAB (protein G-related alpha2M-binding protein) was identified in the S. pyogenes Genome Sequencing data base. The grab gene is present in most S. pyogenes strains and is well conserved. Protein GRAB has typical features of a surface-attached protein of Gram-positive bacteria. It also contains a region homologous to parts of the alpha2M-binding domain of protein G and a variable number of a unique 28-amino acid-long repeat. Using Escherichia coli-produced protein GRAB and synthetic GRAB peptides, the alpha2M-binding region was mapped to the NH2-terminal part of protein GRAB, which is the region with homology to protein G. An isogenic S. pyogenes mutant lacking surface-associated protein GRAB showed no alpha2M binding activity and was attenuated in virulence when injected intraperitoneally in mice. Finally, alpha2M bound to the bacterial surface via protein GRAB was found to entrap and inhibit the activity of both S. pyogenes and host proteinases, thereby protecting important virulence determinants from proteolytic degradation. This regulation of proteolytic activity at the bacterial surface should affect the host-microbe relation during S. pyogenes infections.

Amino Acid Sequence↗

A tumour in the breast: vaccination granuloma as a differential diagnosis.

AIMS: Breast cancer is the most frequent type of cancer in women; special attention is therefore paid to tumours in the breast region. Vaccination granuloma is a differential diagnosis of tumours in the upper part of the breast. METHODS: All granulomatous lesions in the breast region since 1970 were retrieved from the files of the Departments of Pathology at Odense University Hospital and Svendborg Hospital. RESULTS: Fourteen cases with a histology compatible with vaccination granuloma were found. Eight patients had a known history of tetanus vaccination. The tumours were ovoid, or even rod-shaped, and measured between 8x3 mm and 12x10 mm. Histologically, there were necrotic foci surrounded by histiocytes, lymphocytes, and plasma cells. Aluminium was detected by staining with solochrome azurine. CONCLUSIONS: The possibility of a vaccination granuloma should be kept in mind in patients with a palpable tumour in the upper part of the breast, as well as in mammography screening conditions and in follow-up patients after previous treatment for breast cancer.

Adolescent↗

Possible advantages and drawbacks of adding flexible sigmoidoscopy to hemoccult-II in screening for colorectal cancer. A randomized study.

BACKGROUND: Flexible sigmoidoscopy (FS) has been recommended as a screening method to reduce mortality from colorectal cancer (CRC). The present study evaluates the effect of adding FS to the fecal occult blood test Hemoccult-II (H-II) on diagnostic yield of colorectal neoplasia. METHODS: A total of 10,978 normal persons aged 50-75 years were invited to participate, 5495 persons being allocated at random to H-II and FS and 5483 to H-II alone. RESULTS: In spite of a lower compliance (40% versus 56%) for the combined procedure, the diagnostic yield of colorectal neoplasia was higher than for H-II alone (12 CRC versus 4 CRC, and 72 large adenomas versus 14). Within 24-62 months after screening there were fewer CRCs detected after H-II + FS than after H-II alone. The stage distribution was less favorable than in screen-detected cases. CONCLUSION: One FS may not be an optimal way of screening, but FS deserves to be evaluated in randomized population studies including repeated H-II tests in the control arm.

Aged↗

The Virtual Pelvic Floor, a tele-immersive educational environment.

This paper describes the development of the Virtual Pelvic Floor, a new method of teaching the complex anatomy of the pelvic region utilizing virtual reality and advanced networking technology. Virtual reality technology allows improved visualization of three-dimensional structures over conventional media because it supports stereo vision, viewer-centered perspective, large angles of view, and interactivity. Two or more ImmersaDesk systems, drafting table format virtual reality displays, are networked together providing an environment where teacher and students share a high quality three-dimensional anatomical model, and are able to converse, see each other, and to point in three dimensions to indicate areas of interest. This project was realized by the teamwork of surgeons, medical artists and sculptors, computer scientists, and computer visualization experts. It demonstrates the future of virtual reality for surgical education and applications for the Next Generation Internet.

Anatomy↗

Examination of acetaminophen for outpatient management of postoperative pain in children.

We have examined acetaminophen (paracetamol) dosing for outpatient management of posttonsillectomy pain in children. Forty children, 5-15 years of age, undergoing tonsillectomy and their parents were randomly assigned to use a scheduled administration of acetaminophen in weight appropriate doses, 60 mg.kg-1.24h-1 orally, 90 mg.kg-1.24h-1 rectally, or to use acetaminophen 'as needed' according to present standards (control group). Postoperative pain was assessed by the child using the poker chip tool for the first three days after discharge. The prevalence of pain amongst all the children was high. The second day after discharge 22%-64% of the children in the study group and 36%-73% of the children in the control group rated severe pain. Recommended dose ranges of acetaminophen do not provide sufficient pain relief in children following tonsillectomy. Further studies are required to determine, whether higher doses of acetaminophen or analgesics with different analgesic properties will lead to improved analgesia in children following tonsillectomy.

Acetaminophen↗