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Biomedical subjects

A J Hayes

Publications and source records attributed to A J Hayes.

At least 19 recordsLinked to original sources
PubMed2006

Surgical management of soft tissue sarcoma in patients over 80 years.

AIMS: To report outcome on patients over 80years of age with soft tissue sarcoma (STS), with respect to surgical treatment, co-morbidity, complications and survival. METHODS: From a prospective database of 3400 patients with STS presenting over a 13-year period, all patients over 80years of age were identified and reviewed, with respect to tumour characteristics morbidity, mortality and outcome. RESULTS: 128 patients over 80years were treated for STS with 63 referred for treatment of primary disease, of whom 50 underwent resectional surgery. The remaining 65 patients were treated for recurrent or incompletely excised disease. Of the 50 patients treated primarily with surgery, 56% of tumours where high grade and 56% were greater than 10cm in diameter. The overall complication rate was 34%, with a 30-day mortality of 4%. Two- and 5-year survival rates were 56% and 46%, with a local recurrence rate of 22% at a mean follow-up of 22months. CONCLUSION: This patient group presented with poor prognosis tumours that were associated with poor outcomes in the medium to long term. Age need not be considered a contra-indication to radical surgery with curative intent.

Age Factors↗
PubMed2006

Genetic associations between cathepsin D exon 2 C-->T polymorphism and Alzheimer's disease, and pathological correlations with genotype.

Genetic variations represent major risk factors for Alzheimer's disease (AD). While familial early onset AD is associated with mutations in the amyloid precursor protein and presenilin genes, only the e4 allele of the apolipoprotein E (APOE) gene has so far been established as a genetic risk factor for late onset familial and sporadic AD. It has been suggested that the C-->T (224Ala-->Val) transition within exon 2 of the cathepsin D gene (CTSD) might represent a risk factor for late onset AD. The objective of this study was to investigate whether possession of the CTSD exon 2 T allele increases the risk of developing AD, and to determine whether this modulates the amyloid pathology of the disease in conjunction with, or independent of, the APOE e4 allele. Blood samples were obtained from 412 patients with possible or probable AD and brain tissues from a further 148 patients with AD confirmed by postmortem examination. CTSD and APOE genotyping were performed by PCR on DNA extracted from blood, or from frontal cortex or cerebellum in the postmortem cases. Pathological measures of amyloid beta protein (Abeta), as plaque Abeta40 and Abeta42(3) load and degree of cerebral amyloid angiopathy were made by image analysis or semiquantitative rating, respectively. CTSD genotype frequencies in AD were not significantly different from those in control subjects, nor did these differ between cases of early or late onset AD or between younger and older controls. There was no gene interaction between the CTSD T and APOE e4 alleles. The amount of plaque Abeta40 was greater in patients carrying the CTSD T allele than in non-carriers, and in patients bearing APOE e4 allele compared with non-carriers. Possession of both these alleles acted synergistically to increase levels of plaque Abeta40, especially in those individuals who were homozygous for the APOE e4 allele. Possession of the CTSD T allele had no effect on plaque Abeta42(3) load or degree of CAA. Possession of the CTSD T allele does not increase the risk of developing AD per se, but has a modulating effect on the pathogenesis of the disorder by increasing, in concert with the APOE e4 allele, the amount of Abeta deposited as senile plaques in the brain in the form of Abeta40.

Aged↗
PubMed2005

Surgical management of primary and recurrent retroperitoneal liposarcoma.

BACKGROUND: Surgery plays a dominant role in the initial and subsequent treatment of retroperitoneal liposarcoma (RPLS). This study was a review of outcomes of patients treated at the Royal Marsden Hospital. METHODS: Records of all patients who had surgery for RPLS since 1990 were reviewed, with particular attention to local recurrence and disease-specific survival. Patients with primary RPLS and those with recurrent RPLS, who had palliative surgery after a variable number of operations performed elsewhere, were considered separately. RESULTS: Seventy-two patients had surgery for primary RPLS, over half of whom underwent resection of a contiguous organ to achieve clearance. Follow-up of at least 12 months was available for 58 patients. Thirty-four patients had no evidence of recurrence after median follow-up of 26 (range 12-151) months. Low-grade tumour and macroscopic clearance of tumour were significantly associated with a reduced risk of local recurrence and improved survival. Forty-seven patients had palliative surgery for recurrent RPLS. Median survival from time of last operation to death was 27 (range 0-79) months. Follow-up was to a median of 68 (range 14-261) months. CONCLUSION: Patients with low-grade RPLS that has been completely resected at the initial operation have the most favourable prognosis. Palliative resection is worthwhile to treat troublesome symptoms of recurrence.

Adult↗
PubMed2005

In vitro cytotoxicity of selected chemicals commonly produced during fire combustion using human cell lines.

Fire combustion products contain a broad range of chemicals, which have a multitude of possible toxic interactions in humans. The aim of this study was to evaluate the cytotoxicity of selected substances commonly produced during fire combustion. A range of human cell lines and cultures including: skin fibroblasts, HepG2 (liver derived), and A549 (lung derived cells) were used to represent different human target organs. The colorimetric MTS assay (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) was used to detect the cytotoxic effects of selected substances including: acetic acid, ammonia, formaldehyde, hydrobromic acid, hydrochloric acid, hydrofluoric acid, potassium cyanide, sodium fluoride, sodium nitrite, sodium sulphide, and sulphurous acid. In this study, the NOAEC (No Observable Adverse Effect Concentration), IC(10) (10% inhibitory concentration), IC50 (50% inhibitory concentration), and TLC (Total Lethal Concentration) values were determined. The ratio between in vitro IC50 to in vivo human toxicity data (Lowest Lethal Dose-LDLo and Lowest Lethal Concentration--LCLo) was also established. Results indicated a strong relationship between IC50 values on the cell types used: fibroblast and A549 (R2: 0.92), A549 and HepG2 (R2: 0.72), fibroblast and HepG2 (R2: 0.69). Good correlation was obtained between the IC50 against LDLo and LCLo when an appropriate adjustment factor was implemented. Results of this study indicated that in vitro methods could be a potential technique for assessing the toxicity of fire combustion products.

Acetic Acid↗
PubMed2004

Serum vascular endothelial growth factor as a tumour marker in soft tissue sarcoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent tumour-produced angiogenic factor. In this study serum levels of VEGF were measured before treatment and during follow-up in patients undergoing primary treatment for suspected soft tissue sarcoma (STS) to assess the value of serum VEGF as a tumour marker. METHODS: Between April 2001 and September 2002, serum VEGF levels were analysed prospectively in 144 patients undergoing primary treatment (surgery, 123; cytotoxic chemotherapy, ten; oral imatinib, eight; radiotherapy, three) for suspected soft tissue sarcoma. Serum VEGF was measured by immunoassay before treatment, in the immediate postoperative interval in patients undergoing surgery, and during follow-up. Serum VEGF concentrations were also measured in 15 healthy volunteers. RESULTS: Median pretreatment serum VEGF levels were significantly raised in patients with grade 2 and grade 3 sarcomas compared with concentrations in patients with benign lesions (413 and 467 versus 233 pg/ml respectively; P=0.007 and P=0.003 respectively). In patients with tumours that had a high level of VEGF expression before treatment, follow-up measurements reflected disease status after treatment. CONCLUSION: Serum VEGF expression correlated with grade in soft tissue sarcoma and reflected response to treatment.

Antineoplastic Agents↗
PubMed2004

Management of in-transit metastases from cutaneous malignant melanoma.

BACKGROUND: In-transit metastases from cutaneous malignant melanoma (cutaneous or subcutaneous deposits between the primary melanoma and regional lymph nodes) represent late-stage disease, and their treatment should be tailored accordingly. This article reviews the pathology, clinical significance and treatment options for in-transit disease from melanoma. METHODS: An initial Medline search was undertaken using the keywords 'melanoma and in-transit' and 'melanoma and non-nodal regional recurrence'. Additional original articles were obtained from citations in articles identified by the initial search. RESULTS AND CONCLUSION: In-transit metastases carry a poor prognosis. The method of treatment should be tailored to the extent of cutaneous disease. The first line of treatment remains complete excision with negative histopathological margins. There is no need for wide excision. Carbon dioxide laser therapy is valuable for multiple small cutaneous deposits. Isolated limb perfusion has a role for numerous or bulky advanced in-transit metastases in the limbs that are beyond the scope of simpler techniques. Systemic chemotherapy has response rates of about 25 per cent and is reserved for patients for whom surgery is no longer feasible.

Amputation, Surgical↗
PubMed2004

Elastofibroma: a rare soft tissue tumour with a pathognomonic anatomical location and clinical symptom.

BACKGROUND: Elastofibromas are rare benign soft tissue tumours that are almost always located at the inferior pole of the scapula, deep to the serratus anterior muscle. Their anatomical location and a distinctive clinical symptom distinguish them from malignant soft tissue tumours. PATIENTS AND METHODS: A prospective histo-pathological database of all soft tissue tumours referred for treatment to the Royal Marsden Hospital between 1995 and 2003 was searched. Seven patients treated in this institution with a histological diagnosis of elastofibroma were identified. RESULTS: The usual presenting symptoms were that of a mass at the angle of the scapula (7/7), and clunking of the scapula on shoulder abduction (5/7). Pain was an infrequent symptom (1/7). Imaging by CT or MR usually indicated an indeterminate soft tissue neoplasm deep to the peri-scapular muscles, but the histological diagnosis was confirmed pre-operatively by core biopsy in all patients. Subsequent surgical excision was only performed if symptoms were severe. CONCLUSIONS: The clinical presentation of these benign neoplasms is typical and the suspected clinical diagnosis can be confirmed easily by core biopsy. Surgery can be safely reserved for symptomatic patients.

Aged↗
PubMed2004

A comparative study of envelope mastectomy and immediate reconstruction (EMIR) with standard latissimus dorsi immediate breast reconstruction.

BACKGROUND: Latissimus dorsi breast reconstruction has problems with scars at the donor site and on the reconstructed breast. We report the feasibility and aesthetic results of Envelope Mastectomy and Immediate Reconstruction (EMIR), which utilises a single lateral mammary fold incision. PATIENTS AND METHODS: Between 2001 and 2002, 20 EMIRs were performed in 19 patients, one as a staged bilateral procedure. Twenty consecutive patients, matched for body habitus, who had undergone standard latissimus dorsi breast reconstruction by the same surgeon from 1996 to 2000 were used as controls. Patient satisfaction was assessed using a validated Body Image Scale. Standard post-operative photographs were scored by three independent observers. RESULTS: Length of stay and complication rates were equivalent between both groups. Cosmetic self-assessment scores on the Body Image Scale and scores by the independent observers were satisfactory for both groups but no statistically significant difference was observed between groups. CONCLUSIONS: EMIR is a technically feasible and cosmetically acceptable method of immediate breast reconstruction.

Breast Neoplasms↗
PubMed2004

Recombination within a nucleotide-binding-site/leucine-rich-repeat gene cluster produces new variants conditioning resistance to soybean mosaic virus in soybeans.

The soybean Rsv1 gene for resistance to soybean mosaic virus (SMV; Potyvirus) has previously been described as a single-locus multi-allelic gene mapping to molecular linkage group (MLG) F. Various Rsv1 alleles condition different responses to the seven (G1-G7) described strains of SMV, including extreme resistance, localized and systemic necrosis, and mosaic symptoms. We describe the cloning of a cluster of NBS-LRR resistance gene candidates from MLG F of the virus-resistant soybean line PI96983 and demonstrate that multiple genes within this cluster interact to condition unique responses to SMV strains. In addition to cloning 3gG2, a strong candidate for the major Rsv1 resistance gene from PI96983, we describe various unique resistant and necrotic reactions coincident with the presence or absence of other members of this gene cluster. Responses of recombinant lines from a high-resolution mapping population of PI96983 (resistant) x Lee 68 (susceptible) demonstrate that more than one gene in this region of the PI96983 chromosome conditions resistance and/or necrosis to SMV. In addition, the soybean cultivars Marshall and Ogden, which carry other previously described Rsv1 alleles, are shown to possess the 3gG2 gene in a NBS-LRR gene cluster background distinct from PI96983. These observations suggest that two or more related non-TIR-NBS-LRR gene products are likely involved in the allelic response of several Rsv1-containing lines to SMV.

Base Sequence↗
PubMed2003

Toxicity of Australian essential oil Backhousia citriodora (lemon myrtle). Part 2. Absorption and histopathology following application to human skin.

The in vitro percutaneous absorption of the essential oil of lemon myrtle (Backhousia citriodora) has been studied in freshly excised human full-thickness abdominal skin obtained from patients undergoing elective surgery. Absorption of lemon myrtle oil in human skin discs (4.9 cm(2)) was evaluated using a Franz cell diffusion system following topical application of neat lemon myrtle oil (100 microl or 18.29 mg/cm(2)) to the epidermal surface at exposure durations of 1 to 12 h. Gas chromatography mass spectrometry (GCMS) was used as an analytical technique to determine the absorption of lemon myrtle oil components in full-thickness skin. Citral; (consisting of isomers, geranial and neral) was the only component of lemon myrtle oil found to be absorbing into skin at all exposure periods. At the maximum exposure duration of 12 h, the total absorption of citral in the full-thickness skin disc was 0.29+/-0.07 mg/cm(2) (mean+/-S.D., n=4) of the applied dose. Although the absorption of lemon myrtle oil components was limited, haematoxylin and eosin (H&E) staining showed significant losses in the cellular functioning of skin including; losses of integrity and solubilisation of the stratum corneum, cellular necrosis (to 15%) and cellular vacuolation (to 25%) on comparison to control skin. When a formulated product containing 1% lemon myrtle oil (0.18 mg/cm(2)) was applied to human skin discs (4.9 cm(2)) at 8 h exposure the total absorption of citral in the full-thickness skin disc was 5.12+/-0.60 x 10(-4) mg/cm(2) (mean+/-S.D., n=4) of the applied dose. No other components were detected. The histopathological assessment indicated limited damage to epidermal cells. The combination of the above methodologies enabled the generation of data that could be used for a comprehensive evaluation of the toxicity effects of lemon myrtle oil for topical application.

Adipose Tissue↗
PubMed2003

The distribution of Notch receptors and their ligands during articular cartilage development.

We examined the distribution of Notch family members and their ligands during the development of articular cartilage and the growth plate. Notch 1 was expressed by the chondrocytes of the developing articular surface but became increasingly restricted to the deeper layers after birth whilst expression of this family member was restricted to hypertrophic chondrocytes in the growth plate. Notch 2 and 4, Delta and Jagged 2 showed a broadly similar distribution, being present throughout the articular cartilage during development and becoming increasingly restricted to deeper layers with age. Hypertrophic chondrocytes within the growth plate also expressed Notch 2 and 4, Delta and Jagged 2 (which was also expressed in prehypertrophs). Notch 3 and Jagged 1 were absent from developing articular cartilage but were present in deeper layers at later time points (> 1 month) and both receptor and ligand were expressed in hypertrophic chondrocytes at all ages examined. These results highlight the complex Notch signalling interactions that result in the formation of the heterogeneous articular cartilage and allow for the co-ordinated ossification and elongation of the growth plate. Mechanisms by which these processes are controlled are discussed in light of recent advances in the understanding of Notch signalling pathways.

Animals↗
PubMed2002

Stabilization of breast cancer xenograft tumour neovasculature by angiopoietin-1.

Angiopoietin-1 is a promoter of physiological vasculogenesis and angiogenesis because it induces vascular branching and smooth muscle recruitment to newly formed blood vessels. However, angiopoietin-1 expression in tumours appears to be uncommon, and angiopoietin-1 overexpression in cancer cells has been reported to lead to inhibition of xenograft tumour growth. We report here that angiopoietin-1 overexpression resulted in stabilization of tumour edge-associated blood vessels, as it prevented vessel dilation and dissociation of smooth muscle cells from existing vessels. In addition, angiopoietin-1 stimulated an infiltration of mesenchymal cells into the tumours, such that the coverage of microvessels by pericytes increased markedly, and the cancer cells were separated into small masses by the host stroma. The rates of both cancer cell proliferation and apoptosis decreased significantly in the presence of angiopoietin-1. Tie2, the receptor for angiopoietin-1, was found to be present in vascular smooth muscle cells in culture in addition to endothelial cells. These findings suggest that a vascular stabilization effect of angiopoietin-1 accounts for the inhibition of tumour growth.

Angiopoietin-1↗
PubMed2002

Toxicity of Australian essential oil Backhousia citriodora (Lemon myrtle). Part 1. Antimicrobial activity and in vitro cytotoxicity.

The antimicrobial and toxicological properties of the Australian essential oil, lemon myrtle, (Backhousia citriodora) were investigated. Lemon myrtle oil was shown to possess significant antimicrobial activity against the organisms Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, methicillin-resistant S. aureus (MRSA), Aspergillus niger, Klebsiella pneumoniae and Propionibacterium acnes comparable to its major component-citral. An in vitro toxicological study based on the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) cytotoxicity assay was performed. In vitro cytotoxicity testing indicated that both lemon myrtle oil and citral had a very toxic effect against human cell lines: HepG2 (a hepatocarcinoma-derived cell line); F1-73 (a fibroblast cell line derived from normal skin) and primary cell cultures of human skin fibroblasts. Cytotoxicity IC50 (50% inhibitory concentration) values ranged from 0.008 to 0.014% (w/v) at 4 h to 0.003-0.012% (w/v) at 24 h of exposure. The no-observed-adverse-effect level (NOAEL) for lemon myrtle oil was calculated as 0.5 mg/l at 24 h exposure and the RfD (reference dose) was determined as 0.01 mg/l. A product containing 1% lemon myrtle oil was found to be low in toxicity and could potentially be used in the formulation of topical antimicrobial products.

Carcinoma, Hepatocellular↗
PubMed2002

Mapping tightly linked genes controlling potyvirus infection at the Rsv1 and Rpv1 region in soybean.

Soybean mosaic virus (SMV) and peanut mottle virus (PMV) are two potyviruses that cause yield losses and reduce seed quality in infested soybean (Glycine max (L.) Merr.) fields throughout the world. Rsv1 and Rpv1 are genes that provide soybean with resistance to SMV and PMV, respectively. Isolating and characterizing Rsv1 and Rpv1 are instrumental in providing insight into the molecular mechanism of potyvirus recognition in soybean. A population of 1056 F2 individuals from a cross between SMV- and PMV-resistant line PI 96983 (Rsv1 and Rpv1) and the susceptible cultivar 'Lee 68' (rsv1 and rpv1) was used in this study. Disease reaction and molecular-marker data were collected to determine the linkage relationship between Rsv1, Rpv1, and markers that target candidate disease-resistance genes. F2 lines showing a recombination between two of three Rsv1-flanking microsatellite markers were selected for fine mapping. Over 20 RFLP, RAPD, and microsatellite markers were used to map 38 loci at high-resolution to a 6.8-cM region around Rsv1 and Rpv1. This study demonstrates that Rsv1 and Rpv1 are tightly linked at a distance of 1.1 cM. In addition, resistance-gene candidate sequences were mapped to positions flanking and cosegregating with these resistance loci. Based on comparisons of genetic markers and disease reactions, it appears likely that several tightly linked genes are conditioning a resistance response to SMV. We discuss the specifics of these findings and investigate the utility of two disease resistance related probes for the screening of SMV or PMV resistance in soybean.

Chromosome Mapping↗
PubMed2001

Modulation of endothelial cell growth arrest and apoptosis by vascular endothelial growth inhibitor.

Vascular endothelial growth inhibitor (VEGI), a new member of the tumor necrosis factor family, is an endothelial cell-specific gene and a potent inhibitor of endothelial cell proliferation, angiogenesis, and tumor growth. We report here that VEGI mediates the following two activities in endothelial cells: early G(1) arrest in G(0)/G(1) cells responding to growth stimuli, and programmed death in proliferating cells. G(0)/G(1)-synchronized bovine aortic endothelial cells were treated with VEGI before and after the onset of the growth cycle. When the cells were stimulated with growth conditions but treated simultaneously with VEGI, a reversible, early-G(1) growth arrest occurred, evidenced by the lack of late G(1) markers such as hyperphosphorylation of the retinoblastoma gene product and upregulation of the c-myc gene. Additionally, VEGI treatment led to inhibition of the activities of cyclin-dependent kinases CDK2, CDK4, and CDK6. In contrast, VEGI treatment of cells that had entered the growth cycle resulted in apoptotic cell death, as evidenced by terminal deoxytransferase labeling of fragmented DNA, caspase 3 activation, and annexin V staining, all of which were lacking in nonproliferating cells treated with VEGI. Additionally, stress-signaling proteins p38 and JNK were not as fully activated by VEGI in quiescent as compared with proliferating populations. These findings suggest a dual role for VEGI, the maintenance of growth arrest and induction of apoptosis, in the modulation of the endothelial cell cycle.

Animals↗
PubMed2001

The development of articular cartilage: evidence for an appositional growth mechanism.

It is well-established that cartilage grows by a combination of matrix secretion, cell hypertrophy and cell proliferation. The extent to which this growth is by appositional, as opposed to interstitial mechanisms, however, remains unclear. Using the knee joints of the marsupial Monodelphis domestica to study cartilage growth, we have combined an immunohistochemical study of the TGF-beta family of cartilage growth and differentiation factors between 30 days postpartum to 8 months, together with a stereological analysis of cartilage morphology during growth. Furthermore, to gain an insight into the generation of the characteristic zones within cartilage, we have examined the effects of intra-articular administration of bromodeoxyuridine, an agent that is incorporated into DNA during cell division and blocks further cell cycling. During early growth, TGF-beta2 and -beta3 were widely expressed but TGF-beta1 was less so. After the formation of the secondary centre of ossification, all isoforms became more restricted to the upper half of the tissue depth and their distribution was similar to that previously described for IGFs, and PCNA-positive cells. Stereological analysis of tissue sections from the femoral condylar cartilage at 3 and 6 months showed that there was a 17% increase in total cartilage volume but a 31% decrease in cell density on a unit volume basis. Finally, cell-cycle perturbation with BrDU, which was injected into the knee joints of 3-month-old animals and analysed 1 and 4 months post-injection, revealed that the chondrocytes occupying the transitional zone were depleted 1 month post-injection, resulting in thinning of the articular cartilage. This effect was reversed 4 months post-injection. Immunohistochemical analysis revealed that BrDU-treatment altered the expression patterns of all TGF-beta isoforms, with a marked reduction in labelling of TGF-beta1 and -beta3 isoforms in the upper half of the cartilage depth. Overall, the data lends further support to the notion of articular cartilage growing by apposition from the articular surface rather than by interstitial mechanisms.

Animals↗