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Biomedical subjects

M Davies

Publications and source records attributed to M Davies.

At least 19 recordsLinked to original sources
PubMed2004

TGF-beta signal transduction in oro-facial health and non-malignant disease (part I).

The transforming growth factor-beta (TGF-beta) family of cytokines consists of multi-functional polypeptides that regulate a variety of cell processes, including proliferation, differentiation, apoptosis, extracellular matrix elaboration, angiogenesis, and immune suppression, among others. In so doing, TGF-beta plays a key role in the control of cell behavior in both health and disease. In this report, we review what is known about the mechanisms of activation of the peptide, together with details of TGF-beta signal transduction pathways. This review summarizes the evidence implicating TGF-beta in normal physiological processes of the craniofacial complex-such as palatogenesis, tooth formation, wound healing, and scarring-and then evaluates its role in non-malignant disease processes such as scleroderma, submucous fibrosis, periodontal disease, and lichen planus.

Animals↗
PubMed2004

The role of TGF-beta in epithelial malignancy and its relevance to the pathogenesis of oral cancer (part II).

The role of transforming growth factor-beta (TGF-beta) in epithelial malignancy is complex, but it is becoming clear that, in the early stages of carcinogenesis, the protein acts as a potent tumor suppressor, while later, TGF-beta can function to advance tumor progression. We review the evidence to show that the pro-oncogenic functions of TGF-beta are associated with (1) a partial loss of response to the ligand, (2) defects of components of the TGF-beta signal transduction pathway, (3) over-expression and/or activation of the latent complex, (4) epithelial-mesenchymal transition, and (5) recruitment of signaling pathways which act in concert with TGF-beta to facilitate the metastatic phenotype. These changes are viewed in the context of what is known about the pathogenesis of oral cancer and whether this knowledge can be translated into the development of new therapeutic modalities.

Animals↗
PubMed2004

Cause for concern?

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Anti-Bacterial Agents↗
PubMed2004

Metastatic dissemination of human malignant oral keratinocyte cell lines following orthotopic transplantation reflects response to TGF-beta 1.

This study examined the behaviour of nine human malignant oral keratinocyte cell lines following orthotopic transplantation to the floor of the mouth of athymic mice. Tumourigenesis, local spread, and metastatic dissemination were correlated with known cellular responses to transforming growth factor-beta 1 (TGF-beta 1). Six of nine cell lines were tumourigenic; four of these cell lines showed local spread which was characterized by vascular and bone invasion. Metastatic spread was uncommon, with only 9% of animals with primary tumours developing metastases and these were almost exclusively found in the regional lymph nodes; there was one pulmonary metastasis and no liver deposits. Tumour cell behaviour did not reflect the clinical stage of the original tumours. Cell lines that were resistant to TGF-beta 1-induced growth inhibition were more likely to form primary tumours, exhibit local spread, and metastasize than cells that were growth-inhibited by the ligand. The data demonstrate that tumourigenicity and tumour behaviour in this orthotopic mouse model varied between cell lines and that the pattern of local invasion and metastasis was similar to that seen in human oral cancer. Furthermore, cell lines that were refractory to the growth inhibitory effects of TGF-beta 1 behaved more aggressively than cells that underwent ligand-induced cell-cycle arrest.

Adult↗
PubMed2004

The reality of glycaemic control in insulin treated diabetes: defining the clinical challenges.

The benefits of good glycaemic control in both type I and type II diabetes mellitus are undoubtedly proven. Most national bodies have recommended glycaemic targets, with an HbA(1c) to achieve between 6.5 and 7.5%. However, it is well known that even in clinical trials, and routinely in clinical practice, the majority of patients fail to achieve optimal glycaemic control. The reasons for this failure are complex and multifactorial. Healthcare providers often delay the initiation and intensification of insulin unnecessarily. This stems from a fear of causing hypoglycaemia or weight gain in patients, from doubts about patients' self-care abilities and/or from inadequate resources to provide the necessary structured education to support patient self-management. Patients may be poorly adherent to treatment advice-particularly behavioural aspects such as self-monitoring, diet and exercise-although this may itself derive from inadequate access to effective diabetes education. There is, however, a limit to what can be achieved with existing exogenous insulin therapies due to their imperfect pharmacokinetic and pharmacodynamic profiles. Prominent among these imperfections is the problem of variability of effect from injection to injection with basal insulin formulations. Improvements in this area should benefit control and tolerability.

Blood Glucose↗
PubMed2004

Is screening for interferon retinopathy in hepatitis C justified?

BACKGROUND/AIM: In the treatment of hepatitis C, the National Institute for Clinical Excellence advocates use of a combination of interferon alfa and ribavirin for selected patients. Retinopathy is a well recognised side effect of interferon therapy and is characterised by retinal haemorrhages, cotton wool spots, and macular oedema. The aim of this study was to document the incidence and natural history of the retinopathy in patients treated with a long acting (pegylated) interferon and ribavirin for hepatitis C and to assess the need to screen for retinal complications. METHODS: All patients started on treatment from September 2002 to August 2003 were invited to participate in the study. The past medical and ocular history, visual symptoms, and the results of a full ophthalmological assessment performed 3 months after starting treatment were noted. Any patient with retinal changes was followed up at 3 month intervals until the changes resolved. RESULTS: Of the 25 patients examined, four had evidence of retinopathy including deep retinal haemorrhage and cotton wool spots. Two of the patients were diabetic and one hypertensive. None had any visual symptoms and in all four the retinopathy resolved while the patients completed their course of treatment. CONCLUSIONS: The incidence of retinopathy with pegylated interferon is low. The retinal complications resolve while treatment is continued and are asymptomatic. This study does not support routine screening for retinopathy in patients treated with pegylated interferon and ribavirin for hepatitis C.

Adult↗
PubMed2003

Subchondral insufficiency fractures of the femoral head.

The aim of this study was to increase awareness of, and to show the variable clinical and radiological features of, subchondral insufficiency fractures of the femoral head. The clinical and radiological findings in 7 patients with subchondral insufficiency fractures of the femoral head were reviewed retrospectively. The diagnosis was confirmed histologically in 4 patients. Radiographs were performed in all patients, MRI in 5 and scintigraphy in 4 patients. Radiographs showed varying degrees of femoral head collapse in 4 patients. In the remaining 3 patients radiographs showed a normal femoral head, regional osteoporosis and focal sclerosis, respectively. Magnetic resonance imaging showed a low-signal band on T1- and T2-weighted images in the subchondral bone adjacent or parallel to the articular surface associated with bone marrow oedema. Scintigraphy showed increased uptake in the femoral head. Insufficiency fractures of the femoral head are easily overlooked or confused with avascular necrosis and, when there is significant joint destruction, osteoarthritis. Unsuspected insufficiency fracture of the femoral head can lead to significant and rapid loss of bone stock in osteoporotic patients waiting for arthroplasty for osteoarthritis. Increased awareness of this condition will hopefully lead to earlier diagnosis and a successful outcome of conservative treatment.

Adult↗
PubMed2003

Adult small intestinal transplantation in England and Wales.

BACKGROUND: In 1996 two transplantation centres in the UK were commissioned by the National Specialist Commissioning Advisory Group for England and Wales to assess small intestinal transplantation in adults. The joint experience of the two centres is presented. METHODS: Patients with irreversible small intestinal failure and complications of parenteral nutrition, and those with abdominal disease requiring extensive visceral resection, were assessed as candidates and where appropriate listed for surgery. RESULTS: Thirty-six patients were assessed for small intestinal transplantation and, of these, 14 underwent surgery. Twelve patients survived the transplantation procedure. Of these, seven patients were alive at 1 year, five at 3 years and three at 5 years. Three patients remain alive. Patient and graft survival improved with experience; the 1-year survival rate improved in the last 4 years of this experience from 43 to 57 per cent, and the 3-year survival rate from 29 to 43 per cent. CONCLUSION: Small intestinal transplantation is associated with a high mortality rate but may benefit carefully selected patients in whom conservative management is likely to carry a greater mortality rate.

Adult↗
PubMed2003

Differences in the cytokine profiles associated with prostate cancer cell induced osteoblastic and osteolytic lesions in bone.

Prostate adenocarcinoma is associated with the formation of osteoblastic metastases in bone. It is hypothesized that osteoclastogenesis is a critical component in the development of skeletal metastases. These findings, however, were generally noted in predominantly osteolytic lesions. The pathophysiology of osteoblastic lesions remains unknown but the type of bone lesion formed may be influenced by the cytokines produced by prostate tumors. To test this theory, we implanted PC-3 and LAPC-9 cells into the tibias of SCID mice. These mice were sacrificed at 1, 2, 4, 6, and 8 weeks after implantation and histologic analysis was performed on these tibias. PCR analysis was also performed on bulk tumors. The results showed that the PC-3 implanted tibias developed pure osteolytic lesions while the LAPC-9 implanted tibias developed pure osteoblastic lesions on radiographs. Analysis of tibias after injection with PC-3 cells revealed progressive osteolytic lesions with abundant osteoclast activity at 2 weeks and destruction of the proximal tibia at 6 weeks after cell implantation. In contrast, the LAPC-9 cells formed osteoblastic lesions six weeks after cell injection. There were rare osteoclasts prior to the establishment of the osteoblastic lesions but greater osteoclast activity was noted with remodeling of the osteoblastic lesion 8 weeks after implantation of the tumor cells. PCR analysis revealed that PC-3 cells produced RANKL, IL-1, and TNF-alpha, which are associated with osteoclastogenesis. In contrast, LAPC-9 cells produced osteoprotegerin, which blocks osteoclast production and no detectable levels of RANKL or IL-1 and only minimal amounts of TNF-alpha were noted. These cells secreted BMP-2, -4, -6, and IL-6, which are associated with bone formation. These results suggest that the role of the osteoclast in the development of a metastatic lesion is variable depending on the phenotype of the prostate cancer cells, and that tumor-induced osteolysis may not be required for osteoblastic metastases.

Animals↗
PubMed2003

Dural arteriovenous fistulae causing pseudotumour cerebri syndrome in an elderly man.

The clinical presentation of dural arteriovenous fistulae (DAVF) is dependent on their location and the nature of their venous drainage. The latter plays a critical part in determining whether or not the fistula gives rise to intracranial hypertension, which is present in only a minority of cases. We present a case of the pseudotumour cerebri syndrome in an elderly man with bilateral intracranial DAVF supplied by the occipital arteries. Cerebral angiography was required for definitive diagnosis, and to characterise the abnormal venous drainage. The pathophysiology of intracranial hypertension in DAVF is discussed.

Aged↗
PubMed2003

Cysticercoids of five species of Raillietina Fuhrmann, 1920 (Cestoda: Davaineidae) in ants, Pheidole sp., from emu farms in Australia.

Cysticercoids of five species of Raillietina, R. australis (Krabbe, 1869) Fuhrmann, 1924, R. beveridgei O'Callaghan, Davies & Andrews, 2000, R. chiltoni O'Callaghan, Davies & Andrews, 2000, R. dromaius O'Callaghan, Davies & Andrews, 2000 and R. mitchelli O'Callaghan, Davies & Andrews, 2000, parasitic in the emu Dromaius novaehollandiae Latham, are described. Each species was identified on the basis of the number and size of the rostellar hooks, which correspond to those of adult worms. Cysticercoids were recovered from the haemocoele of the gaster of ants belonging to the genus Pheidole (Hymenoptera: Formicidae) in Australia. There was a trend towards an inverse relationship between the size of the cysticercoids and the parasite burden in the intermediate host.

Animals↗
PubMed2003

A human flora-associated rat model of the breast-fed infant gut.

OBJECTIVES: Bacterial colonization of the infant gut may have important influences on the development of gastrointestinal, respiratory, and allergic disease. Early diet is a major determinant of the gut microflora. It is very difficult to carry out studies in human infants that can investigate the interaction of diet, flora, and mucosa. In this study we have developed an infant human flora-associated (IHFA) rat model to allow such investigation. METHODS: Germ-free infant rats were infected with fecal bacteria from exclusively breast-fed infants and were maintained on a modified infant formula for 8 weeks. The fecal and cecal contents were collected and compared with feces of breast-fed infants for bacterial populations, bacterial metabolites, and enzymes and for the ability to inhibit adhesion of pathogenic bacteria to human mucosal cells. RESULTS: The IHFA cecum and feces were dominated by lactic acid bacteria, Bifidobacterium, and lactobacilli, which were representative of the infant feces. The fecal short-chain fatty acid profile was dominated by acetic and lactic acid in a similar manner to human infant feces. Other bacterial metabolites were similar to those of the human infant. Rat intestinal samples were able to inhibit the adhesion of pathogens to mucosal cells, but to a lesser extent than the human samples. CONCLUSIONS: This IHFA infant model of the intestinal flora of the breast-fed infant is considered valid for studying the effect of diet on bacterial colonization and metabolism.

Animals↗
PubMed2002

Laparoscopic evaluation of testicular mobility as a guide to management of intra-abdominal testes.

The optimal management of intra-abdominal testes is the subject of an ongoing debate as the result of widespread use of laparoscopy since early 1990's. A simple laparoscopic technique uses cord mobility to act as a guide to cord length and therefore predict the success of a conventional orchidopexy in cases of true intra-abdominal testes. In the technique described, the testis is displaced by stretching the testes to overly the opposite internal inguinal ring. Over a 3-year period, a total of 36 boys with 38 intra-abdominal testes, confirmed laparoscopically, were prospectively assessed. The reported "stretching maneuver" was carried out in all cases. Successful conventional orchidopexy as predicted by a positive stretch maneuver was carried out in 20 testes. When the stretch maneuver failed, conventional 2-stage open operation was done in 3 patients and Fowler-Stephens orchidopexies for the remaining 13 children. A simple test determining testicular mobility assessed during laparoscopic evaluation of intra-abdominal testes provides information of significant importance upon which the correct surgical approach can be based.

Adolescent↗