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Biomedical subjects

R Hardwick

Publications and source records attributed to R Hardwick.

16 recordsLinked to original sources
PubMed2006

A prospective comparison of multidisciplinary treatment of oesophageal cancer with curative intent in a UK cancer network.

AIMS: Combined modality therapy (with chemotherapy+/-radiotherapy) has become a standard treatment for locally advanced oesophageal cancer. However, there appears to be no compelling evidence for one treatment type or combination to suit all and at this time the clinical multi-disciplinary team (MDT) forms an important role in selecting optimal therapies for the individual. This prospective comparison in one cancer network, looks at the outcomes of this decision making process. METHODS: Over a five year period 1998-2003, data were prospectively collected on all 330 consecutive patients, referred to a tertiary specialised MDT for whom curative treatment was the planned intent. Patients were managed according to an agreed local protocol and allocated to receive one of 5 treatments: surgery alone (S), pre-operative chemotherapy (C+S), pre-operative chemo-radiotherapy (CRT+S), definitive chemo-radiotherapy (CRT) and radiotherapy alone (RT). RESULTS: The 2 and 5 year survival for all patients receiving potentially curative treatment were 49% and 26% respectively. With 2 and 5 year survival for S, CRT+S, C+S, CRT and RT being 53,21; 57,40; 37,27; 50,27; 23,0 months respectively. Of the surgical therapies, mortality was highest in the CRT+S group, versus C+S and S; 12.5%, 1.6%, 4.5% respectively (p=0.025). Non-surgical based therapies had more than double the incidence of local relapses compared to surgical based therapies; however the CRT group had an overall survival comparable with S alone. The commonest sites of distant relapse were liver (56%), lung (38%), bone (32%) and non-regional lymph nodes (24%). CONCLUSION: The results suggest that in patients who are deemed unfit for surgical intervention, definitive chemoradiotherapy remains a viable alternative; they also lend further support to selected case triple modality therapy. These areas should be further examined in the context of randomised controlled phase III trials.

Aged↗
PubMed2006

Pilot study of preoperative combined modality treatment for locally advanced operable oesophageal carcinoma: toxicities and long-term outcome.

AIMS: Paclitaxel, a radiosensitiser, has significant activity in oesophageal cancer. We aimed to conduct a feasibility study of preoperative chemoradiation using paclitaxel, cisplatin and 5-fluorouracil (5-FU). MATERIALS AND METHODS: Sixteen eligible patients were enrolled. Infusional 5-FU, paclitaxel and cisplatin were given for 6 weeks before and concurrent with radiation. Conformal radiotherapy was delivered in two phases (45 Gy in 25 fractions). RESULTS: A total of 62.5% of the patients experienced Grade 3-4 toxicities, 50% required admission; one patient died during the neo-adjuvant phase. Twelve (75%) patients had oesophagectomy, and two (12.5%) died after surgery. Pathological complete remission (PCR) and minimal residual disease were observed in 25% (95% CI 0.5-49.5%) and 18% (95% CI 0-38%) of patients, respectively, who underwent surgery. The median survival was 39.7 months (95% CI 15, not reached); 1-, 2-, 3-, and 4-year survivals were 75% (95% CI 56.5-99.5), 56.3% (36.5-86.7), 50% (30.6-81.6), and 50% (30.6-81.6), respectively. CONCLUSION: Paclitaxel, cisplatin and 5-FU (TCF)-chemoradiation is an active regimen; the current dose schedule tested is associated with unacceptable toxicity, and cannot be recommended for routine clinical use.

Adenocarcinoma↗
PubMed2000

Mosaic rearrangement of chromosome 18: characterization by FISH mapping and DNA studies shows trisomy 18p and monosomy 18p both of paternal origin.

Structural abnormalities of chromosome 18p mainly consist of isochromosomes of the short arm, which result in tetrasomy 18p. Trisomy 18p is much rarer, and less well characterized. We report on a 12-year-old girl with minor facial anomalies, delayed development, abnormal hands, atopic dermatitis, and hearing loss. She was mosaic for two abnormal cell lines in peripheral blood. In 90% of cells, a dicentric chromosome with duplication of the whole short arm of chromosome 18 resulted in trisomy 18p; 10% of cells had monosomy 18p, arising from a t(14;18)(p11;q11). FISH mapping, with multiple region specific and locus specific probes from the short and long arm of chromosome 18, showed that the structure of the dicentric chromosome 18 was 18pter-->18q23::18q11-->18pter. DNA polymorphisms for chromosome 18 showed that the abnormalities of chromosome 18 were paternal in origin. Combining all results, we could link the trisomy 18p and monosomy 18p to a common origin via a complex series of events in an early mitosis.

Abnormalities, Multiple↗
PubMed2000

Periodontal repair in dogs: effect of transforming growth factor-beta 1 on alveolar bone and cementum regeneration.

BACKGROUND: Transforming growth factor-beta (TGF-beta) represents a family of growth-modulating proteins with fundamental roles in connective tissue and bone development. The objective of this study was to evaluate the potential for regeneration of alveolar bone and cementum following surgical implantation of recombinant human TGF-beta 1 (rhTGF-beta 1). METHOD: Bilateral, critical size, supra-alveolar periodontal defects in 5 beagle dogs were surgically implanted with rhTGF-beta 1 in a calcium carbonate carrier (CaCO3) or with carrier alone. The animals were euthanized at 4 weeks postsurgery and block-biopsies of the defects were processed for histologic and histometric analysis. RESULTS: Surgical implantation of rhTGF-beta 1 resulted in minimal, if any, stimulation of alveolar bone or cementum regeneration. Linear bone and cementum regeneration in rhTGF-beta 1-treated defects was 1.2+/-0.6 and 0.01+0.01 mm, respectively. Corresponding values for the controls were 1.0+/-0.6 and 0.01+/-0.03 mm. CONCLUSIONS: The results suggest that, under the conditions (dose, carrier, defect type) evaluated here, treatment of periodontal defects in beagle dogs with rhTGF-beta 1 may be of limited clinical benefit.

Alveolar Process↗
PubMed2000

Alveolar ridge repair in a canine model using rhTGF-beta 1 with barrier membranes.

In both normal and membrane-assisted situations, healing events are modulated by the activity of endogenous protein molecules known as cytokines. Due to its mitogenic and chemotactic characteristics, the addition of rhTGF-beta 1 should increase the rate of osteogenesis or increase the potential for bone regeneration in oral osseous defects. This study evaluates the effects of an osteoconductive biodegradable matrix incorporating human recombinant transforming growth factor beta 1 (rhTGF-beta 1) in conjunction with barrier membranes on bone regeneration in canine alveolar ridge defects. A matrix of calcium carbonate and hydroxyethyl starch served as the carrier for test concentrations of 2.0 micrograms/0.8 ml and 20.0 micrograms/0.8 ml of rhTGF-beta 1. One surgically prepared site in each of 13 adult male fox-hounds received 1 of 4 experimental treatment regimens, with 6 sites utilizing barrier membranes. Four sites in each of 2 additional animals, two containing carrier matrix only and 2 with the additional barrier membrane, served as controls. Specimens were retrieved after 2 months of healing and processed for routine light microscopy. The quantity and composition of regenerated bone was examined. Analysis of variance revealed a statistically significant increase (P < 0.05) in the development of bone with the use of rhTGF-beta 1. Likewise, a statistically significant increase in regeneration was found in membrane-protected sites over nonmembrane-protected sites. No statistically significant difference was noted between the low and high dose treatments. The authors conclude that the use of rhTGF-beta 1 in conjunction with a barrier membrane greatly enhances bone regeneration in osseous oral defects.

Alveolar Process↗
PubMed1998

Opposite effects of recombinant human transforming growth factor-beta 1 on bone regeneration in vivo: effects of exclusion of periosteal cells by microporous membrane.

The efficacy of local delivery of recombinant human transforming growth factor-beta 1 (rhTGF-beta 1) to promote bone regeneration, with or without cellular contribution from the periosteum, was evaluated in transosseous defects. Implantation of rhTGF-beta 1 into 5 mm in diameter "critical size defects" in the rat mandible resulted in a dose-dependent (0.1-20 micrograms/defect) bone bridging at both 12 and 24 days, independent of the type of delivery system [3% methyl cellulose gel, porous CaCO3 particles, or poly(lactide-co-glycolide) beads]. The bridging, however, never exceeded 24% at 12 days or 34% after 24 days. In contrast, when access of cells from the periosteum to the defect was prevented by means of microporous expanded polytetrafluoroethylene barrier membranes (GORE-TEX membrane), rhTGF-beta 1 caused a dose-dependent inhibition of bone regeneration. The bioactivity of the growth factor was confirmed by implantation of 5 or 10 micrograms rhTGF-beta 1 in 12 mm in diameter bicortical defects in rabbit calvaria, which resulted in complete bone healing within 28 days, whereas control defects displayed a bridging of 40%-50%. The findings support the concept, based on in vitro experiments by others, that TGF-beta 1 primarily has a proliferative effect on cells already committed to the osteoblastic lineage, but also imply that TGF-beta 1 may be inhibitory to induction of osteogenic cells in vivo.

Animals↗
PubMed1998

Periodontal repair in dogs: effect of recombinant human transforming growth factor-beta1 on guided tissue regeneration.

This study evaluated alveolar bone and cementum regeneration following surgical implantation of recombinant human transforming growth factor-beta1 (rhTGF-beta1) in conjunction with guided tissue regeneration (GTR). Supraalveolar, critical size, periodontal defects were surgically created around the 3rd and 4th mandibular premolar teeth in right and left jaw quadrants in 5 beagle dogs. Alternate jaw quadrants in consecutive animals received rhTGF-beta1, in a CaCO3/hydroxyethyl starch carrier with GTR, or carrier with GTR alone (control). 20 microg of rhTGF-beta1 in buffer solution was incorporated into approximately 0.8 ml of carrier for each defect scheduled to receive rhTGF-beta1. Animals were sacrificed at week 4 postsurgery and tissue blocks were harvested and processed for histometric analysis. Clinical healing was generally uneventful. Minor membrane exposures were observed. Defects with membrane exposure displayed an inflammatory infiltrate underneath the membrane. Bone regeneration of trabecular nature, apparent in all animals, was generally limited to the very apical aspect of the defects. Cementum regeneration was limited without obvious differences between experimental conditions. Comparing rhTGF-beta1, to control defects, statistically significant differences were found for area (1.8+/-0.4 and 1.3+/-0.6 mm2, respectively; p<0.05) and density (0.3+/-0.1 and 0.2+/-0.03, respectively; p<0.05) of alveolar bone regeneration. Observed differences are small and represent a clinically insignificant potential for enhanced regeneration in this preclinical model. Within the limitations of study, it may be concluded that rhTGF-beta1 has a restricted potential to enhance alveolar bone regeneration in conjunction with GTR.

Alveolar Bone Loss↗
PubMed1996

Clinical and microbiological observations of early polytetrafluoroethylene membrane exposure in guided bone regeneration. Case reports in primates.

Premature membrane exposure at one week is described in 3 Macaca mulatta monkeys as part of a sequence of experiments on guided bone regeneration. Clinical sequelae include redness, edema, and tissue slough. Bacteroides fragilis, Streptococcus pneumoniae, Prevotella intermedia, and Staphylococcus intermedius were detected at all prematurely exposed sites. Pseudomonas maltophilia, Strept, pneumoniae, and P. intermedia were the predominant organisms detected and consisted of more than 10% of the total anaerobic count.

Alveolar Bone Loss↗
PubMed1995

Devices for dentoalveolar regeneration: an up-to-date literature review.

Regeneration of periodontal and alveolar ridge defects utilizing barrier membranes has become well established in clinical dentoalveolar reconstruction. Application of this technique has evolved from the concept of separating tissues during healing to that of providing a healing environment capable of regeneration of functional structures. The biomaterial characteristics and design of membranes employed in this technique play an important role in establishing and maintaining this environment. Barrier membranes must incorporate specific features that address the biological, mechanical, and clinical use requirements involved in regenerative treatment. Although nondegradable materials require a second surgical procedure for removal, these materials simplify certain aspects of development, production, and clinical regenerative treatment for some applications. Degradable materials introduce specific considerations and limitations regarding material selection, design, and clinical application. The progressive breakdown of degradable membranes results in dynamic changes in the mechanical and biocompatibility profiles of these materials. With present technology, these factors may limit use of degradable materials to specific applications. Membrane materials, therefore, should be selected based on a thorough understanding of the benefits and limitations inherent to the material(s) in relation to the functional requirements of specific clinical applications.

Alveolar Process↗
PubMed1994

Periodontal repair in dogs: space provision by reinforced ePTFE membranes enhances bone and cementum regeneration in large supraalveolar defects.

Regeneration of alveolar bone and cementum following reconstructive therapy with reinforced space providing expanded polytetrafluorethylene (ePTFE) membranes was evaluated in supraalveolar mandibular premolar periodontal defects in five beagle dogs. The surgically-created defects in contralateral jaw quadrants were randomly assigned to receive the dome-shaped membrane or serve as surgical control. Flaps were positioned to completely submerge the teeth and sutured. The dogs were sacrificed 8 weeks after surgery and tissue blocks including teeth and surrounding structures processed for histology. Membrane treated defects in two animals became exposed and infected leaving intact quadrants in three dogs for histometric analysis. Parameters evaluated included defect height, height and area of regenerated alveolar bone, height of regenerated cementum, root resorption, and ankylosis. Mean defect height approximated 4.1 mm. Mean height (+/- s.d.) of regenerated alveolar bone amounted to 2.9 +/- 0.6 and 0.6 +/- 0.2 mm for membrane and control defects, respectively (P = 0.006). Corresponding values for bone area were 1.4 +/- 0.7 and 0.4 +/- 0.4 mm2 (P = 0.02). Cementum regeneration was observed in all teeth averaging (+/- s.d.) 1.6 +/- 0.3 mm for membrane treated and 0.1 +/- 0.1 mm for control defects (P = 0.01). Small amounts of root resorption were seen in all teeth with no significant difference between treatments. Ankylosis was noticed in three membrane treated and two control teeth. The present study provides a biologic rationale for space provision for enhanced bone and cementum regeneration in periodontal defects subject to reconstructive therapy.

Alveolar Bone Loss↗
PubMed1992

A new syndrome? Unusual facies, hooked clavicles, 13 pairs of ribs, widened metaphyses, square shaped vertebral bodies and communicating hydrocephalus.

Two strikingly similar twin sisters presented with characteristic facial anomalies and distinctive radiographic findings. The occurrence of this unique pattern of malformations in two sisters with unaffected parents suggests recessive inheritance. They most likely represent a previously unrecognised malformation syndrome.

Abnormalities, Multiple↗
PubMedDate not supplied

Osseointegration of titanium implants in bone regenerated in membrane-protected defects: a histologic study in the canine mandible.

In the present histologic study of the mandibles of five foxhounds, 15 nonsubmerged titanium implants were placed in bone regenerated in extended membrane-protected defects during a 6-month healing period. The clinical and radiographic evaluation demonstrated that all 15 implants achieved functional ankylosis within 3 months following implant placement. Subsequently, eight implants were restored with fixed partial dentures and were functionally loaded for 6 months, and seven implants were left unrestored. At the completion of the study, the histologic analysis demonstrated osseointegration with direct bone-to-implant contact for all 15 implants. Therefore, it can be concluded that bone regenerated in membrane-protected defects responds to implant placement like nonregenerated bone, and that this bone is capable of bearing and sustaining functional load. The histologic comparison of restored and unrestored sites demonstrated no apparent differences concerning bone remodeling activities. Furthermore, control sites without implant placement demonstrated bone atrophy underneath the membranes with a thin cortical layer and sparse bone trabeculae. Thus, it can also be concluded that the placement of an implant into regenerated bone stimulated bone maturation and bone remodeling, whereas implant loading did not influence bone remodeling in the present study model.

Alveolar Bone Loss↗