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Biomedical subjects

S Dawson

Publications and source records attributed to S Dawson.

At least 19 recordsLinked to original sources

Lethal outbreak of disease associated with feline calicivirus infection in cats.

Recently, in the USA, virulent mutants of feline calicivirus (FCV) have been identified as the cause of a severe and acute virulent systemic disease, characterised by jaundice, oedema and high mortality in groups of cats. This severe manifestation of FCV disease has so far only been reported in the USA. However, in 2003, an outbreak of disease affected a household of four adult cats and an adult cat from a neighbouring household in the UK. Three of the adult cats in the household and the neighbouring cat developed clinical signs including pyrexia (39.5 to 40.5 degrees C), lameness, voice loss, inappetence and jaundice. One cat was euthanased in extremis, two died and one recovered. A postmortem examination of one of the cats revealed focal cellulitis around the right hock and right elbow joints. The principal finding of histopathological examinations of selected organs from two of the cats was disseminated hepatocellular necrosis with mild inflammatory infiltration. Immunohistology identified FCV antigen in parenchymal and Kupffer cells in the liver of both animals and in alveolar macrophages of one of them. In addition, calicivirus-like particles were observed by electron microscopy within the hepatocytes of one cat. FCV was isolated from two of the dead cats and from the two surviving cats. Sequence analysis showed that they were all infected with the same strain of virus, but that it was different from strains of FCV associated with the virulent systemic disease in cats in the USA. The outbreak was successfully controlled by quarantine in the owner's house.

Animals↗

Recombination of Feline calicivirus within an endemically infected cat colony.

To understand the evolution of the family Caliciviridae, the persistence of Feline calicivirus (FCV) was studied within an endemically infected cat colony. Polymerase and capsid sequences were analysed for 34 FCV isolates obtained over a 4 year period. Initially, the colony was infected with one strain of virus, but a second distinct strain was later identified. Subsequently, the emergence of a recombinant virus was observed, containing elements of both of the strains circulating within the colony. The recombination event mapped close to the ORF1/ORF2 junction. This is consistent with recombination in other caliciviruses, suggesting a common mechanism within this family. This is the first report of recombination within the genus Vesivirus in the family Caliciviridae and the first time that a recombination event has been observed where the parental strains have also been identified.

Animals↗

Construct and face validity of MIST-VR, Endotower, and CELTS: are we ready for skills assessment using simulators?

BACKGROUND: Video trainers may best offer visually realistic laparoscopic simulation, whereas virtual reality (VR) modules may best provide multidimensional objective measures of performance. This study compares the construct and face validity of three different laparoscopic simulators. METHODS: Subjects were voluntarily enrolled at the Learning Center during the 2004 SAGES annual meeting. Each subject completed two repetitions of a single task on each of three simulators, MIST-VR, Endotower, and CELTS; performance scores were automatically generated and recorded. Scores of individuals with various levels of experience were compared to determine construct validity for each simulator. Experience was defined according to four parameters: (a) PGY level, (b) fellowship training, (c) basic laparoscopic cases, and (d) advanced laparoscopic cases. Subjects rated each simulator regarding six face validity (realism of simulation) parameters using a 10-point Likert scale (10 = best rating) and participant scores were compared to previously established expert scores (proficiency goals for training). RESULTS: Ninety-one attendees completed the study. Construct validity was demonstrated for all three simulators; significant differences in scores were detected according to one parameter for MIST-VR, two parameters for Endotower, and all four parameters for CELTS. Face validity was rated as good to excellent for all three simulators (7.0 +/- 0.3 for MIST-VR, 7.9 +/- 0.3 for Endotower [p < 0.001 vs MIST-VR], and 8.7 +/- 0.1 for CELTS [p = 0.001 vs MIST-VR, p = 0.01 vs Endotower]); 6%, 0%, and 36% of "expert" participants obtained expert scores on MIST-VR, Endotower, and CELTS, respectively. CONCLUSIONS: All three simulators demonstrated significant construct and reasonable face validity. Although virtual reality holds great promise to expand the scope of laparoscopic simulation, current interfaces may limit their utility for assessment. Computer-enhanced video trainers may offer an improved interface while incorporating useful multidimensional metrics. Further work is needed to establish standards for appropriate skills assessment methods and performance levels using simulators.

Adult↗

Diagnostic value of cytology of bronchoalveolar fluid for lung diseases of sheep.

Bronchoalveolar lavage fluid was collected postmortem from the lungs of 113 sheep, and total and differential cell counts were analysed in relation to the presence of gross and microscopic lung pathology. The diffuse lung diseases, maedi and adenomatosis, were both characterised by an increase in overall cellularity and by increases in the percentages of lymphocytes and neutrophils, respectively. Focal parasitic lung disease was characterised by an increase in the percentage of eosinophils and mast cells. Consolidated lung lesions were characterised by a slight increase in cellularity but no change in the differential cell profile. In regions of parasitised and consolidated lungs without lesions the differential cell profile was consistent with focal lung pathology, although the slight increase in cellularity observed in the consolidated regions was not observed in the regions without lesions. A decision tree was developed to facilitate the interpretation and indicate the likely predictive capacity of the differential cytology of the fluid.

Animals↗

Higgs-boson production with one bottom-quark jet at hadron colliders.

We present total rates and kinematic distributions for the associated production of a single bottom quark and a Higgs boson at the Fermilab Tevatron and CERN Large Hardon Collider. We include next-to-leading order QCD corrections and compare the results obtained in the four and five flavor number schemes for parton distribution functions.

Journal Article↗

New approaches to catheter navigation for interventional radiology simulation.

For over 20 years, interventional methods have improved the outcomes of patients with cardiovascular disease. However, these procedures require an intricate combination of visual and tactile feedback and extensive training periods. In this paper, we describe a series of novel approaches that have lead to the development of a high-fidelity simulation system for interventional neuroradiology. In particular we focus on a new approach for real-time deformation of devices such as catheters and guidewires during navigation inside complex vascular networks. This approach combines a real-time incremental Finite Element Model, an optimization strategy based on substructure decomposition, and a new method for handling collision response in situations where the number of contacts points is very large. We also briefly describe other aspects of the simulation system, from patient-specific segmentation to the simulation of contrast agent propagation and fast volume rendering techniques for generating synthetic X-ray images in real-time.

Algorithms↗

MELD scores do not predict patient morbidity while on the liver transplant waiting list.

The goals of this study were to assess waitlist morbidity in terms of the frequency of health care services utilized by patients while on the liver transplant (LTX) waiting list and to determine whether that utilization can be predicted by the Model for End-Stage Liver Disease (MELD). Sixty-three noncomatose subjects were followed from waitlist placement until death, change in status, LTX, or study discontinuance. Health care events included doctor/clinic visits, labs, outpatient/inpatient tests and procedures, and hospital/intensive care unit days. Listing MELD scores and LTX MELD scores were examined against the number of health care event occurrences within 60 days of listing and 60 days of LTX, respectively, as were changes in MELD scores between listing and LTX and differences in the number of occurrences between the two time points. The only significant correlations noted were between LTX MELD scores and number of hospital days near LTX (r = .360, P = .046) and between LTX MELD scores and the sum total number of occurrences near LTX (r = .370, P = .044). These results suggest that MELD scores do not appear to predict morbidity in terms of health care utilization in patients awaiting LTX. Developing a system capable of predicting waitlist morbidity may lead to the implementation of medical interventions aimed at circumventing foreseeable complications and/or crises in patients awaiting LTX.

Humans↗

Sirolimus conversion after liver transplantation: improvement in measured glomerular filtration rate after 2 years.

METHODS: We reviewed our prospectively maintained database of 2005 liver transplantations. Therapy was either started de novo or converted from calcineurin inhibitors (CNIs) to sirolimus as the main immunosuppressive agent for nephrotoxicity or rejection. Glomerular filtration rate (GFR) was determined with iodine 125-labeled sodium isthalamate (Glofil-125), and serum creatinine concentration was obtained before and 3 months after transplantation, and yearly in both groups. Sirolimus levels were 10 to 15 ng/mL in patients at less than 3 months after transplantations and 5 to 10 ng/mL in the remaining patients. All patients received mycophenolate mofetil as maintenance therapy. RESULTS: Data for 29 patients in the de novo group and 35 in the conversion group were reviewed. Patients in the de novo group demonstrated an acute cellular rejection rate of 17.2%, 40% of which were steroid resistant. In this group, 48.2% discontinuation of sirolimus was necessary because of adverse effects. Patients in the conversion group demonstrated an acute cellular rejection rate of 2.8% and a 34.3% rate of sirolimus discontinuation. Seventeen (56.7%) patients at 1 year and 8 (44.4%) patients at 2 years demonstrated continued improvement in GFR. In the conversion group, case-control analysis did not demonstrate a significant difference in GFR and serum creatinine concentration (P > .05) at 1 and 2 years after conversion. At the time of review, no patients in the conversion group required hemodialysis. CONCLUSIONS: Conversion to sirolimus therapy is an effective strategy in improving renal function in patients with CNI-induced nephrotoxicity and can be done without increased rejection. Most of our patients (65.7%) tolerated sirolimus conversion. Of these, 56.7% and 44.4% demonstrated continued increase in GFR with the CNI-free regimen at 1 and 2 years, respectively. Long-term, large-population, prospective, randomized, controlled studies should further validate these results.

Creatinine↗

Simulated laparoscopy using a head-mounted display vs traditional video monitor: an assessment of performance and muscle fatigue.

BACKGROUND: The direction of visual gaze may be an important ergonomic factor that affects operative performance. We designed a study to determine whether a head-mounted display (HMD) worn by the surgeon would improve task performance and/or reduce muscle fatigue during a laparoscopic task when compared to the use of a traditional video monitor display (VMD). METHODS: Surgical residents (n = 30) were enrolled in the study. A junior group, consisting of 15 postgraduate year (PGY) = 1 subjects with no previous laparoscopic experience, and a senior group, consisting of 15 PGY 4 and PGY 5 subjects with experience, completed a laparoscopic task that was repeated four times using the Computer Enhanced Laparoscopic Training System (CELTS). Groups alternated between using the HMD with the task placed in a downward frontal position and the VMD with the task at a 30 degrees lateral angle. The CELTS module assessed task completion time, depth perception, path length of instruments, response orientation, motion smoothness; the system then generated an overall score. Electromyography (EMG) was used to record sternocleidomastoid muscle activity. Display preference was surveyed. RESULTS: The senior residents performed better than the junior residents overall on all parameters (p < 0.05) except for motion smoothness, where there was no difference. In both groups, the HMD significantly improved motion smoothness when compared to the VMD (p < 0.05). All other parameters were equal. There was less muscle fatigue when using the VMD (p < 0.05). We found that 66% of the junior residents but only 20% of the senior residents preferred the HMD. CONCLUSIONS: The CELTS module demonstrated evidence of construct validity by differentiating the performances of junior and senior residents. By aligning the surgeon's visual gaze with the instruments, HMD improved smoothness of motion. Experienced residents preferred the traditional monitor display. Although the VMD produced less muscle fatigue, inexperienced residents preferred the HMD, possibly because of improved smoothness of motion.

Computer Simulation↗

MRI and plain radiography in the assessment of displaced fractures of the waist of the carpal scaphoid.

We treated 50 patients with fractures of the waist of the scaphoid in a below-elbow plaster cast for up to 13 weeks. Displacement of the fragments was assessed independently by two observers using MRI and radiographs performed within two weeks of injury. The MRI assessments showed that only the measurement of sagittal translation of the fragments and an overall assessment of displacement had satisfactory inter- and intra-observer reproducibility and revealed that nine of the 50 fractures were displaced. Only three of the 49 fractures with adequate follow-up failed to unite, and all were displaced with more than 1 mm of translation in the sagittal plane. If the MRI assessment of displacement of the fracture was used as the measurement of choice, assessment of displacement on the initial scaphoid series of radiographs showed a sensitivity of between 33% and 47% and a positive predictive value of between 27% and 86%. Neither observer was able correctly to identify more than 33% to 47% of the displaced fractures from the plain radiographs. Although the overall assessment of displacement and gapping and translation in the coronal plane on the plain radiographs influenced the rate of union, none of these parameters identified all three fractures which failed to unite. We conclude that the assessment of displacement of scaphoid fractures on MRI can probably be used to assess the likelihood of union although the small number of nonunions limits the power of the study. In contrast, the assessment of displacement on routine radiography is inaccurate and of less value in predicting union.

Casts, Surgical↗

Solution crystallisation via a submerged liquid-liquid phase boundary: oiling out.

In many situations the process of crystallisation from solution is known to occur via metastable crystalline states (polymorphs or solvates). Here we present what we believe to be a novel example of small molecule crystallisation in which the initial separation of a solute rich liquid phase precedes the crystallisation event. We believe this occurs because a submerged liquid-liquid phase boundary is accessible within the metastable zone of the crystal nucleation process.

Journal Article↗

Proteasomal interactors control activities as diverse as the cell cycle and glutaminergic neurotransmission.

The six regulatory non-redundant ATPases in the base of the 19 S regulator of the 26 S proteasome belong to the AAA superfamily of ATPases. Yeast two-hybrid genetic screens, biochemical analyses and cell biological studies have identified and characterized new interactors of the human S6 (rpt3) and S8 (rpt6) ATPases of the 19 S regulator of the 26 S proteasome. The S6 ATPase interacts with gankyrin. This protein is found in purified human 26 S proteasomes and in a smaller complex(es) containing CDK4 and free S6 ATPase. Gankyrin overexpression causes the phosphorylation of the retinoblastoma protein (pRb) and the release of E2F transcription factor to trigger the expression of DNA synthesis genes. Gankyrin is oncogenic in nude mice and is overexpressed in hepatocellular carcinoma cells (HCCs). The S8 ATPase interacts with members of the large Homer-3 protein family. There are three Homer genes; the Homer 1 and 2 gene products control trafficking and calcium-store-related functions of metabotropic glutamate receptors (e.g. mGluR1alpha). Homer-3A11 by binding to the S8 ATPase brings mGluR1alpha to the 26 S proteasome for degradation. The degradation of mGluR1alpha is blocked by proteasomal inhibitors and by overexpression of the N-terminus of Homer which binds to the receptor. The S8 ATPase and mGluR1alpha are co-localized in Purkinje dendrites in rat cerebellum. The data are discussed in terms of the regulation of the cell cycle and glutaminergic receptor functions by the 26 S proteasome.

Adenosine Triphosphatases↗

DNA vaccination against feline calicivirus infection using a plasmid encoding the mature capsid protein.

Feline calicivirus (FCV), a member of the diverse family Caliciviridae, is a respiratory and oral pathogen of cats. Although conventional FCV vaccines are available, there are some safety and efficacy problems associated with their use. The potential of DNA vaccination against FCV infection was therefore explored. Four cats were inoculated intramuscularly with three 100 microg doses, 2 weeks apart, with a plasmid (pF9VAC) containing the mature capsid protein gene of FCV strain F9. Four control cats received the same plasmid lacking the FCV gene insert. All eight cats showed clinical signs following heterologous challenge with FCV strain LS027. However, rectal temperatures and general clinical sign scores were significantly lower in vaccinates compared to controls, and there was a marked difference in ulcer distribution between the two groups. Although no serological responses were detected in either group prior to challenge, post-challenge titres in the vaccinated group were generally higher. The results indicate that partial protection against a calicivirus is possible by DNA vaccination but that other approaches to enhance efficacy such as the use of cytokine genes or prime-boost protocols may also be required.

Animals↗

Early graft function after pediatric liver transplantation: comparison between in situ split liver grafts and living-related liver grafts.

BACKGROUND: The systematic application of living-related and cadaveric, in situ split-liver transplantation has helped to alleviate the critical shortage of suitable-sized, pediatric donors. Undoubtedly, both techniques are beneficial and advantageous; however, the superiority of either graft source has not been demonstrated directly. Because of the potential living-donor risks, we reserve the living donor as the last graft option for pediatric recipients awaiting liver transplantation. Inasmuch as no direct comparison between these two graft types has been performed, we sought to perform a comparative analysis of the functional outcomes of left lateral segmental grafts procured from these donor sources to determine whether differences do exist. METHODS: A retrospective analysis of all liver transplants performed at a single institution between February 1984 and January 1999 was undertaken. Only pediatric (<18 years) recipients of left lateral segmental grafts procured from either living-related (LRD) or cadaveric, in situ split-liver (SLD) donors were included. A detailed analysis of preoperative, intraoperative, and postoperative variables was undertaken. Survival was estimated using the Kaplan-Meier method, and comparison of variables between groups was undertaken using the t test of Wilcoxon rank sum test. RESULTS: There were no significant differences in the preoperative variables between the 39 recipients of SLD grafts and 34 recipients of LRD grafts. The donors did differ significantly in mean age, ABO blood group matching, and preoperative liver function testing. Postoperative liver function testing revealed significant early differences in aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, prothrombin time, and alkaline phosphatase, with grafts from LRD performing better than those from SLD. SLD grafts also had significantly longer ischemia times and a higher incidence of graft loss owing to primary nonfunction and technical complications (9 vs. 2, P<0.05). However, six of these graft losses in the SLD group were because of technical or immunologic causes, which, theoretically, should not differ between the two groups. Furthermore, these graft losses did not negatively impact early patient survival as most patients were successfully rescued with retransplantation (30-day actuarial survival, 97.1% SLD vs. 94.1% LRD, P=0.745). In the surviving grafts, the early differences in liver function variables normalized. CONCLUSIONS: Inherent differences in both donor sources exist and account for differences seen in preoperative and intraoperative variables. Segmental grafts from LRD clearly performed better in the first week after transplantation as demonstrated by lower liver function variables and less graft loss to primary nonfunction. However, the intermediate function (7-30 days) of both grafts did not differ, and the early graft losses did not translate into patient death. Although minimal living-donor morbidity was seen in this series, the use of this donor type still carries a finite risk. We therefore will continue to use SLD as the primary graft source for pediatric patients awaiting liver transplantation.

Adult↗

Next-to-leading order results for tt macro h production at the Tevatron.

We compute the Omicron(alpha(3)(s)) inclusive total cross section for the process pp macr0 -->tt macro h in the standard model, at the square root of s(H) = 2 TeV. The next-to-leading order corrections drastically reduce the renormalization and factorization scale dependence of the Born cross section and slightly decrease the total cross section for renormalization and factorization scales between m(t) and 2m(t).

Journal Article↗