Search PubMed⌕ Search

Biomedical subjects

M Thornton

Publications and source records attributed to M Thornton.

At least 19 recordsLinked to original sources
PubMed2005

Benefits of activity and virtual reality based balance exercise programmes for adults with traumatic brain injury: perceptions of participants and their caregivers.

OBJECTIVE: To explore multi-dimensional benefits of exercise participation perceived by adults with traumatic brain injury (TBI) and their caregivers. METHODS: Adults (n=27, aged 18-66) with moderate or severe TBI 6 months or more earlier participated in focus groups following 6 weeks of an activity-based (ABE) or a virtual reality (VR) delivered balance exercise programme. Family members and care providers participated in separate focus groups. Perceptions related to programme participation as well as balance confidence and lower extremity function were extracted from focus group verbatim and quantitative scales, respectively. OUTCOMES: Benefits in three domains, psychosocial, physical and programme, were identified from transcription and analyses of focus group verbatim. Improvements were noted in balance confidence and function in both groups. Substantially greater enthusiasm and knowledge was expressed by participants in the VR group and their caregivers. CONCLUSIONS: Both exercise programmes offered benefits in addition to improved balance. The VR participants had greater improvements on quantitative measures and provided more comments expressing enjoyment and improved confidence. Applications in terms of community reintegration and quality of life are discussed.

Adolescent↗
PubMed2003

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties.

Herpes simplex virus type-1 (HSV1) in which the neurovirulence factor ICP34.5 is inactivated has been shown to direct tumour-specific cell lysis in several tumour models. Such viruses have also been shown to be safe in Phase I clinical trials by intra-tumoral injection in glioma and melanoma patients. Previous work has used serially passaged laboratory isolates of HSV1 which we hypothesized may be attenuated in their lytic capability in human tumour cells as compared to more recent clinical isolates. To produce ICP34.5 deleted HSV with enhanced oncolytic potential, we tested two clinical isolates. Both showed improved cell killing in all human tumour cell lines tested compared to a laboratory strain (strain 17+). ICP34.5 was then deleted from one of the clinical isolate strains (strain JS1). Enhanced tumour cell killing with ICP34.5 deleted HSV has also been reported by the deletion of ICP47 by the up-regulation of US11 which occurs following this mutation. Thus to further improve oncolytic properties, ICP47 was removed from JS1/ICP34.5-. As ICP47 also functions to block antigen processing in HSV infected cells, this mutation was also anticipated to improve the immune stimulating properties of the virus. Finally, to provide viruses with maximum oncolytic and immune stimulating properties, the gene for human or mouse GM-CSF was inserted into the JS1/34.5-/47- vector backbone. GM-CSF is a potent immune stimulator promoting the differentiation of progenitor cells into dendritic cells and has shown promise in clinical trials when delivered by a number of means. Combination of GM-CSF with oncolytic therapy may be particularly effective as the necrotic cell death accompanying virus replication should serve to effectively release tumour antigens to then induce a GM-CSF-enhanced immune response. This would, in effect, provide an in situ, patient-specific, anti-tumour vaccine. The viruses constructed were tested in vitro in human tumour cell lines and in vivo in mice demonstrating significant anti-tumour effects. These were greatly improved compared to viruses not containing each of the modifications described. In vivo, both injected and non-injected tumours showed significant shrinkage or clearance and mice were protected against re-challenge with tumour cells. The data presented indicate that JS1/ICP34.5-/ICP47-/GM-CSF acts as a powerful oncolytic agent which may be appropriate for the treatment of a number of solid tumour types in man.

Animals↗
PubMed2002

A randomised comparison of a foot pump and low-molecular-weight heparin in the prevention of deep-vein thrombosis after total knee replacement.

Patients who undergo total knee replacement (TKR) are at high risk of venous thromboembolism. Low-molecular-weight heparins (LMWH) are the most suitable chemical prophylactic agents but there are some uncertainties about their safety and effectiveness. The foot pump offers an alternative. We randomised 229 patients undergoing primary, unilateral TKR to receive either the A-V Impulse foot pump or enoxaparin, a LMWH. Ascending venography was undertaken between the sixth and eighth postoperative day in 188 patients without knowledge of the randomisation category. The prevalence of venographic deep-vein thrombosis was 58% (57/99) in the foot-pump group and 54% (48/89) in the LMWH group which was not statistically significant. There were four cases of proximal thrombi and two of fatal pulmonary emboli in the foot-pump group and none in the LMWH group. There were fewer haemorrhagic complications and soft-tissue effects in the foot-pump group. We conclude that the neither method provides superior prophylaxis.

Aged↗
PubMed2001

P1 and NR1 plasmid replication during the cell cycle of Escherichia coli.

Replication patterns of the miniP1 plasmid pZC176, the miniNR1 plasmid pRR933, and the high-copy miniNR1 derivative pRR942 were examined during the Escherichia coli cell division cycle and compared to the cycle-specific replication pattern of a minichromosome and the cycle nonspecific pattern of pBR322. In E. coli cells growing with doubling times of 40 and 60 min, the miniP1 plasmid was found to replicate with a slight periodicity during the division cycle. The periodicity was not nearly as pronounced as that of the minichromosome, was not affected by the presence of a minichromosome, and was not evident in cells growing more rapidly with a doubling time of 25 min. Both miniNR1 plasmids, pRR933 and pRR942, replicated with patterns indistinguishable from that of pBR322 and clearly different from that of the minichromosome. It is concluded that both P1 and NR1 plasmids can replicate at all stages of the cell cycle but that P1 displays a slight periodicity in replication probability in the cycle of slower growing cells. This periodicity does not appear to be coupled to a specific age in the cycle, but could be associated with the achievement of a specific cell mass per plasmid. During temperature shifts of a dnaC(Ts) mutant, the miniP1 plasmid and pBR322 replicated with similar patterns that differed from that of the minichromosome, but were consistent with a brief eclipse between rounds of replication.

Bacterial Proteins↗
PubMed2001

Cell-cycle research with synchronous cultures: an evaluation.

The baby-machine system, which produces new-born Escherichia coli cells from cultures immobilized on a membrane, was developed many years ago in an attempt to attain optimal synchrony with minimal disturbance of steady-state growth. In the present article, we put forward a model to describe the behaviour of cells produced by this method, and provide quantitative evaluation of the parameters involved, at each of four different growth rates. Considering the high level of selection achievable with this technique and the natural dispersion in interdivision times, we believe that the output of the baby machine is probably close to optimal in terms of both quality and persistence of synchrony. We show that considerable information on events in the cell cycle can be obtained from populations with age distributions very much broader than those achieved with the baby machine and differing only modestly from steady state. The data presented here, together with the long and fruitful history of findings employing the baby-machine technique, suggest that minimisation of stress on cells is the single most important factor for successful cell-cycle analysis.

Amino Acids↗
PubMed2001

Creation of genome-wide protein expression libraries using random activation of gene expression.

Here we report the use of random activation of gene expression (RAGE) to create genome-wide protein expression libraries. RAGE libraries containing only 5 x 10(6) individual clones were found to express every gene tested, including genes that are normally silent in the parent cell line. Furthermore, endogenous genes were activated at similar frequencies and expressed at similar levels within RAGE libraries created from multiple human cell lines, demonstrating that RAGE libraries are inherently normalized. Pools of RAGE clones were used to isolate 19,547 human gene clusters, approximately 53% of which were novel when tested against public databases of expressed sequence tag (EST) and complementary DNA (cDNA). Isolation of individual clones confirmed that the activated endogenous genes can be expressed at high levels to produce biologically active proteins. The properties of RAGE libraries and RAGE expression clones are well suited for a number of biotechnological applications including gene discovery, protein characterization, drug development, and protein manufacturing.

Cell Line↗
PubMed2001

Type I laryngeal cleft: late presentation.

Laryngeal cleft anomalies are rare congenital defects of the posterior laryngotracheal wall that usually present with a history of recurrent respiratory tract infections during the early neonatal period. Presentation of type I clefts can be subtle and subsequently can result in late diagnosis or indeed failure to present. We report on the case of a type I laryngeal cleft presenting with a history of recurrent lower respiratory tract infections and severe gastro-oesophageal reflux disease, at 19 years of age. This is the oldest documented initial presentation of a congenital laryngeal cleft, and emphasizes the importance of maintaining a suspicion of the diagnosis into early adulthood. We further highlight the role of gastro-oesophageal reflux disease in the presentation of laryngeal clefts.

Adult↗
PubMed2000

Effect of oxiplex* films (PEO/CMC) on adhesion formation and reformation in rabbit models and on peritoneal infection in a rat model.

OBJECTIVE: To assess the efficacy of Oxiplex (FzioMed, Inc., San Luis Obispo, CA) barriers. DESIGN: Film of polyethylene oxide and carboxymethylcellulose (Oxiplex) were tested for strength and tissue adherence. Films were selected for evaluation in models for biocompatability and adherence. Three films were selected for evaluation in efficacy studies, and one was evaluated for effects on bacterial peritonitis. Handling characteristics of Oxiplex film were evaluated via laparoscopy. SETTING: University laboratory. PATIENT(S): Rabbits, rats, pigs. INTERVENTION(S): Placement of Oxiplex prototypes at the site of injury. MAIN OUTCOME MEASURE(S): Mechanical properties, biocompatibility, tissue adherence, adhesion development, infection potentiation, and device handling. RESULT(S): Mechanical tests indicated that tensile strength and elongation were inversely correlated. All films tested had excellent tissue adherence properties. Selected films, based on residence time and biocompatibility, prevented adhesion formation in all animals and were highly efficacious in preventing adhesion reformation. The optimal Oxiplex prototype prevented adhesion reformation in 91% of the animals. This Oxiplex film, dyed to allow visualization, prevented adhesion reformation and did not affect bacterial peritonitis. In a laparoscopic model, the Oxiplex film, delivered in FilmSert forceps, via a 5.0-mm trocar, rapidly unfurled and could be easily applied to tissue with strong adherence. CONCLUSION(S): These data show development of an adhesion prevention material that is tissue adherent, can be placed via laparoscopy, and does not affect host resistance.

Absorbable Implants↗
PubMed2000

The radiographic quantitation of aortic valve calcification: implications for assessing bioprosthetic valve calcification in vitro.

Calcification of natural aortic and bioprosthetic heart valves is a poorly understood phenomenon that results in valvular obstruction and tissue failure. We describe a non-destructive quantitative computed microtomographic (QCT) technique for determining both calcium content and local calcium distribution within explanted valves. As a reference standard, a dual-energy x-ray absorptiometry (DEXA) system with an accuracy demonstrated to be within 1% of the true calcium mass of test material was used to obtain the total calcium content of 24 human aortic valve cusps recovered at autopsy from patients aged 51-80 years. These cusps were then scanned using our unique volume QCT scanner, with multiple x-ray projections acquired by rotating the explanted tissue through a single axis of rotation. A three-dimensional cross-sectional map was reconstructed for each cusp. Voxel size was 0.003 mm3 and a calibration phantom was used to calculate calcium content. The minimum detection limit for calcium mass was 1 mg within the whole cusp. The DEXA and QCT scans were compared with respect to total calcium content, which ranged from 0 to 15 mg. An excellent correlation between the two independent techniques was demonstrated with an r2 value of 0.94 (p < 0.001). Non-destructive microtomographic CT scanning provided excellent volumetric density measurements, with quantitative 3D images permitting an assessment of any individual area of the cusp for calcium content and spatial distribution. This new approach to valve tissue analysis allows for subsequent histologic assessment.

Absorptiometry, Photon↗
PubMed2000

Surface geometric analysis of anatomic structures using biquintic finite element interpolation.

The surface geometry of anatomic structures can have a direct impact upon their mechanical behavior in health and disease. Thus, mechanical analysis requires the accurate quantification of three-dimensional in vivo surface geometry. We present a fully generalized surface fitting method for surface geometric analysis that uses finite element based hermite biquintic polynomial interpolation functions. The method generates a contiguous surface of C2 continuity, allowing computation of the finite strain and curvature tensors over the entire surface with respect to a single in-surface coordinate system. The Sobolev norm, which restricts element length and curvature, was utilized to stabilize the interpolating polynomial at boundaries and in regions of sparse data. A major advantage of the current method is its ability to fully quantify surface deformation from an unstructured grid of data points using a single interpolation scheme. The method was validated by computing both the principal curvature distributions for phantoms of known curvatures and the principal stretch and principal change of curvature distributions for a synthetic spherical patch warping into an ellipsoidal shape. To demonstrate the applicability to biomedical problems, the method was applied to quantify surface curvatures of an abdominal aortic aneurysm and the principal strains and change of curvatures of a deforming bioprosthetic heart valve leaflet. The method proved accurate for the computation of surface curvatures, as well as for strains and curvature change for a surface undergoing large deformations.

Animals↗
PubMed1999

Assessment of maintenance therapy with reduced doses of PTH(1-34) in combination with a raloxifene analogue (LY117018) following anabolic therapy in the ovariectomized rat.

This experiment was designed to evaluate the ability of a raloxifene analogue (RA), LY117018, with or without reduced dosing of human parathyroid hormone (hPTH)(1-34) to maintain gains in bone mass after a fully anabolic treatment regimen given to aging osteopenic rats. Six-month-old rats were ovariectomized (ovx) or sham-operated (sham). After 1 month, ovx rats were treated with an anabolic regimen consisting of subcutaneous hPTH(1-34) 80 microg/kg/day and oral raloxifene 3 mg/kg/day, each given 5 days/week for 3 months. Thereafter, the treated ovx rats went on to an 8 week maintenance phase of treatment with either RA alone at the same dose, hPTH(1-34) at a reduced dosing interval (twice a week), or a combination of the two. Bone mineral density (BMD) was measured ex vivo at four skeletal sites, lumbar spine (L2-4), proximal hemipelvis, whole femur, and tibia, by dual-energy X-ray densitometry. All four sites showed a similar pattern of response. After the 3 month anabolic phase, the sham group had significantly higher BMD values than ovx rats at all skeletal sites (p < or = 0.002). The ovx rats treated with PTH + RA during the anabolic phase of the protocol had significantly higher BMD than the sham group in the femur, tibia, and spine (p < or = 0.02) and higher but not significantly different values in the pelvis. Following the 2 month maintenance phase, comparisons were made with the PTH-RA group at the end of the anabolic phase. Decrements in BMD were seen in all three maintenance therapy groups, but they were not statistically significant in the RA plus reduced PTH dose group. However, reduced hPTH(1-34) dosing and RA alone resulted in significant reductions of bone mass measurements at several skeletal sites during the maintenance phase. We conclude that the raloxifene analogue LY117018 may be useful in maintaining bone mass in aging ovx rats following anabolic therapy with hPTH(1-34) and raloxifene analogue, but that this strategy only allows for dose reduction of hPTH(1-34) rather than its discontinuation.

Absorptiometry, Photon↗
PubMed1999

Anti-Kaposi's sarcoma and antiangiogenic activities of sulfated dextrins.

Delivery of the sulfated polysaccharide dextrin 2-sulfate by the intraperitoneal route to the lymphatic circulation resulted in a clinically significant improvement in Kaposi's sarcoma in three patients. Our in vitro studies show that although sulfated dextrins do not interfere with the growth of isolated human umbilical vein endothelial cells, they do inhibit the morphological differentiation of endothelial cells into tubes as well as reduce new vessel formation in a placental angiogenesis assay. The antiangiogenic effect of dextrin 6-sulfate is greater than that of dextrin 2-sulfate and is independent of their anti-human immunodeficiency virus type 1 activities.

Anti-HIV Agents↗
PubMed1999

The addition of a raloxifene analog (LY117018) allows for reduced PTH(1-34) dosing during reversal of osteopenia in ovariectomized rats.

To test the hypothesis that an antiresorptive agent might reduce the dosing requirement for an anabolic drug during reversal of osteopenia due to estrogen deficiency, the following experiment was conducted in 6-month-old female rats. Ovariectomy or sham surgery was performed and the following six experimental groups were studied. Untreated (SHAM) or ovariectomized (OVX) animals served as control groups. Four weeks post-OVX, osteopenic rats (now 7 months old), were treated in one of four experimental protocols: human parathyroid hormone (hPTH(1-34)), 80 microg/kg/day, given by subcutaneous injection 5 days/week; a selective estrogen receptor modulator (SERM), raloxifene analog LY117018 (RA), 3 mg/kg/day, given by gavage 5 days/week; and two combinations of LY117018 at the same dose and frequency with hPTH(1-34) (same dose, 5 times/week) and a reduced dosing interval of hPTH(1-34) (same dose, 2 times/week). After 12 weeks of treatment, the four experimental groups were sacrificed at age 10 months. SHAM and OVX controls were also studied at 7 and 10 months of age. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at four skeletal sites: two mixed cortical/trabecular sites (femur and tibia) and two predominantly trabecular sites (lumbar spine and pelvis). The differences in BMD were consistent at all four sites. RA alone maintained BMD at all skeletal sites, but the results were not significantly improved over OVX controls, at age 10 months. hPTH(1-34) injections given 5 days/week resulted in BMD increments significantly higher than in either OVX or SHAM controls (p < 0.001). While the RA did not enhance the anabolic effects of full doses of hPTH(1-34), the addition of RA treatment to twice-weekly hPTH(1-34) dosing resulted in BMD increments at all four skeletal sites that were similar to the more intensive anabolic regimen of hPTH(1-34) therapy given 5 times/week. Therefore, an antiresorptive agent such as SERMs may potentially reduce the pharmacologic doses of PTH needed to reverse estrogen deficiency-induced osteopenia.

Animals↗
PubMed1998

Reduction of the viral load of HIV-1 after the intraperitoneal administration of dextrin 2-sulphate in patients with AIDS.

OBJECTIVE: To determine the safety and efficacy of the sulphated polysaccharide, dextrin 2-sulphate, when delivered to the lymphatic circulation by the peritoneal route. DESIGN: An open Phase I/II dose-escalation clinical study in which six patients with AIDS were treated with seven courses of dextrin 2-sulphate each lasting 1 month. METHODS: During each course of treatment, the drug was administered daily for 28 days using an intraperitoneal catheter. Viral load was measured at frequent intervals using a plasma tissue culture infectious dose (TCID) assay, a cellular TCID assay, p24 antigenaemia, HIV-1 RNA and HIV-1 DNA. Plasma beta-chemokine levels were also measured. RESULTS: Dose escalation was completed without toxicity. A total of 7 patient-months of treatment were completed. With increasing doses of dextrin 2-sulphate, the infectious plasma viraemia, cellular viraemia and p24 antigenaemia all fell during the period of drug administration, but with no significant change in HIV-1 RNA. This was associated with increased plasma levels of macrophage inflammatory protein (MIP)-1alpha and MIP-1beta. Dextrin 2-sulphate accumulated in peritoneal macrophages and induced the release of MIP-1alpha and MIP-1beta from these cells in vitro. These beta-chemokines could have augmented the cell surface-mediated anti-HIV-1 effect of dextrin 2-sulphate in vivo by binding to and blocking the CC-chemokine receptor-5. A second fall in infectious plasma viraemia, cellular viraemia, p24 antigenaemia and HIV-1 RNA was seen at day 100 which was then sustained for several months. A clinical improvement in Kaposi's sarcoma was also seen. CONCLUSIONS: Our results suggest that the intraperitoneal administration of dextrin 2-sulphate can reduce the replication of HIV-1 in patients with AIDS. With increasing doses of dextrin 2-sulphate, the fall in viral load was seen during the period of drug administration and again 2 months after completing treatment.

AIDS-Related Opportunistic Infections↗