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Biomedical subjects

M Davies

Publications and source records attributed to M Davies.

At least 19 recordsLinked to original sources
PubMed2007

Ten years experience of one-stage restorative proctocolectomy for ulcerative colitis.

BACKGROUND: Ileal-pouch anal anastomosis has an established role in the treatment of ulcerative colitis. Controversy exists regarding the routine use of a diverting ileostomy. The aim of this study was to review the clinical and functional outcome of patients undergoing restorative proctocolectomy in the absence of a diverting ileostomy (one-stage). MATERIALS AND METHODS: Between 1990 and 1999, 87 patients with ulcerative colitis underwent a one-stage restorative proctocolectomy. The median age at the time of operation was 34 years (range 12-64 years) and median follow-up was 36 months (range 24-144 months). The clinical notes were reviewed retrospectively. RESULTS: The median in-patient stay was 15 days (range 9-36). There were no post-operative deaths. The complication rate within 30 days of surgery approximated to 40%. The median daytime pouch evacuation rate was 5. Only 13% of patients had to empty their pouch at night on a regular basis. Pelvic sepsis secondary to anastomotic leakage was the most commonly encountered problem, occurring in 15 patients. Small bowel obstruction was encountered in ten patients. One pouch required excision for a recurrent pouch-vaginal fistula. CONCLUSION: Despite refinements in the surgical technique, restorative proctocolectomy is associated with significant morbidity. For a selected group of patients undergoing an ileo-anal anastomosis, a defunctioning ileostomy may be avoided.

Adolescent↗
PubMed2007

The impact of lifestyle factors on reproductive performance in the general population and those undergoing infertility treatment: a review.

This evidence-based review focuses on the impact of potentially modifiable, non-communicable lifestyle factors on reproductive performance in the general population and the infertile population undergoing assisted reproductive technology (ART) treatment. The impact of several lifestyle factors including; age, weight, smoking, diet, exercise, psychological stress, caffeine consumption, alcohol consumption and exposure to environmental pollutants are included in the review. The databases of Medline, PubMed and Cinahl were searched to identify relevant publications. There is strong evidence that age, weight and smoking impact on general health and adversely on reproductive performance. However there is a need for further research focusing specifically on the relationship between diet and various levels of exercise on reproductive performance. There are several other factors such as psychological stress, caffeine consumption, alcohol consumption and exposure to environmental pollutants that have been implicated but the evidence is equivocal. It is concluded that lifestyle modification can assist couples to conceive spontaneously or optimize their chances of conception with ART treatment.

Female↗
PubMed2006

An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in exon 17 of the NF1 gene (c.2970-2972 delAAT): evidence of a clinically significant NF1 genotype-phenotype correlation.

Neurofibromatosis type 1 (NF1) is characterized by cafe-au-lait spots, skinfold freckling, and cutaneous neurofibromas. No obvious relationships between small mutations (<20 bp) of the NF1 gene and a specific phenotype have previously been demonstrated, which suggests that interaction with either unlinked modifying genes and/or the normal NF1 allele may be involved in the development of the particular clinical features associated with NF1. We identified 21 unrelated probands with NF1 (14 familial and 7 sporadic cases) who were all found to have the same c.2970-2972 delAAT (p.990delM) mutation but no cutaneous neurofibromas or clinically obvious plexiform neurofibromas. Molecular analysis identified the same 3-bp inframe deletion (c.2970-2972 delAAT) in exon 17 of the NF1 gene in all affected subjects. The Delta AAT mutation is predicted to result in the loss of one of two adjacent methionines (codon 991 or 992) ( Delta Met991), in conjunction with silent ACA-->ACG change of codon 990. These two methionine residues are located in a highly conserved region of neurofibromin and are expected, therefore, to have a functional role in the protein. Our data represent results from the first study to correlate a specific small mutation of the NF1 gene to the expression of a particular clinical phenotype. The biological mechanism that relates this specific mutation to the suppression of cutaneous neurofibroma development is unknown.

Adolescent↗
PubMed2006

Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury.

Chondroitin sulfate proteoglycans (CSPGs) are inhibitory extracellular matrix molecules that are upregulated after CNS injury. Degradation of CSPGs using the enzyme chondroitinase ABC (ChABC) can promote functional recovery after spinal cord injury. However, the mechanisms underlying this recovery are not clear. Here we investigated the effects of ChABC treatment on promoting plasticity within the spinal cord. We found robust sprouting of both injured (corticospinal) and intact (serotonergic) descending projections as well as uninjured primary afferents after a cervical dorsal column injury and ChABC treatment. Sprouting fibers were observed in aberrant locations in degenerating white matter proximal to the injury in regions where CSPGs had been degraded. Corticospinal and serotonergic sprouting fibers were also observed in spinal gray matter at and below the level of the lesion, indicating increased innervation in the terminal regions of descending projections important for locomotion. Spinal-injured animals treated with a vehicle solution showed no significant sprouting. Interestingly, ChABC treatment in uninjured animals did not induce sprouting in any system. Thus, both denervation and CSPG degradation were required to promote sprouting within the spinal cord. We also examined potential detrimental effects of ChABC-induced plasticity. However, although primary afferent sprouting was observed after lumbar dorsal column lesions and ChABC treatment, there was no increased connectivity of nociceptive neurons or development of mechanical allodynia or thermal hyperalgesia. Thus, CSPG digestion promotes robust sprouting of spinal projections in degenerating and denervated areas of the spinal cord; compensatory sprouting of descending systems could be a key mechanism underlying functional recovery.

Animals↗
PubMed2006

Nutrition knowledge and body mass index.

The purpose of this study was to investigate the relationship between nutrition knowledge and body mass index (BMI). The General Nutrition Questionnaire was distributed to 500 individuals on the database of a large general practice. Results demonstrated that there was no significant correlation between levels of nutrition knowledge and BMI; however, a high level of nutrition knowledge was found among the sample. This suggests that a knowledge deficit may not be the most significant factor preventing overweight individuals from adopting a healthier diet and questions the utility of purely educational approaches to dietary behaviour change. Evidence-based health behaviour change techniques are discussed.

Adult↗
PubMed2006

Results of early surgical intervention after suboptimal ankle fracture fixation.

Ankle fractures are common injuries and commonly require operative stabilisation. The aim of ankle fracture fixation should be reduction and stabilisation, as for any periarticular fracture. Anatomical reduction will lead to good long-term results, but non-anatomically reduced fractures will lead to a poor functional outcome and development of osteoarthritis. We reviewed eight cases of non-anatomical ankle fixations that were revised by M.D. over a 4-year period. All were revised within 1 year of initial fixation. Clinical scoring for functional outcome was performed using the American Orthopaedic Foot and Ankle Society rating system for the ankle and hindfoot. All patients reported improved function after the revision procedure. We conclude that revision surgery is justified if suboptimal fixation is encountered within 12 months of the original surgery.

Adult↗
PubMed2006

Function and effect of bone morphogenetic protein-7 in kidney bone and the bone-vascular links in chronic kidney disease.

In two independent and separate studies, we have shown that renal injury and chronic kidney disease (CKD) directly inhibit skeletal anabolism, and that stimulation of bone formation decreased the serum phosphate. In the first study, the serum Ca PO(4), parathyroid hormone (PTH), and calcitriol were maintained normal after renal ablation in mice, and even mild renal injury equivalent to stage 3 CKD decreased bone formation rates. More recently, these observations were rediscovered in low-density lipoprotein receptor null (LDLR-/-) mice fed high-fat/cholesterol diets, a model of the metabolic syndrome (hypertension, obesity, dyslipidemia and insulin resistance). We demonstrated that these mice have vascular calcification (VC) of both the intimal atherosclerotic type and medial calcification. We have also shown that VC is made worse by CKD and ameliorated by bone morphogenetic protein-7 (BMP-7). The finding that high-fat fed LDLR-/- animals with CKD had hyperphosphatemia which was prevented in BMP-7-treated animals lead us to examine the skeletons of these mice. It was found that significant reductions in bone formation rates were associated with high-fat feeding, and superimposing CKD resulted in the adynamic bone disorder (ABD), while VC was made worse. The effect of CKD to decrease skeletal anabolism (decreased bone formation rates and reduced number of bone modelling units) occurred despite secondary hyperparathyroidism. The BMP-7 treatment corrected the ABD and hyperphosphatemia, owing to BMP-7-driven stimulation of skeletal phosphate deposition reducing plasma phosphate and thereby removing a major stimulus to VC. A pathological link between abnormal bone mineralization and VC through the serum phosphorus was demonstrated by the partial effectiveness of directly reducing the serum phosphate by a phosphate binder that had no skeletal action. Thus, in the metabolic syndrome with CKD, a reduction in bone forming potential of osteogenic cells leads to the ABD producing hyperphosphatemia and VC, processes ameliorated by BMP-7, in part through increased bone formation and skeletal deposition of phosphate and in part through direct actions on vascular smooth muscle cells. We have demonstrated that the processes leading to vascular calcification begin with even mild levels of renal injury affecting the skeleton before demonstrable hyperphosphatemia and that they are preventable and treatable. Therefore, early intervention in the skeletal disorder associated with CKD is warranted and may affect mortality of the disease.

Animals↗
PubMed2006

Phaeochromocytoma in pregnancy.

Hypertension during pregnancy is a common problem, causing significant maternal and fetal morbidity and mortality. Pre-eclampsia is by far the most common cause, affecting 5-10% of primigravid women. Phaeochromocytoma is a rare endocrine tumour causing hypersecretion of noradrenaline, adrenaline and/or dopamine. It is extremely rare during pregnancy and may be misdiagnosed with potentially catastrophic consequences. Delayed diagnosis remains a significant source of maternal and fetal morbidity and mortality. Recognition is critical, as the majority of maternal deaths have occurred when the diagnosis has been overlooked. Diagnosis of phaeochromocytoma is achieved by detecting increased catecholamines and metabolites (metanephrine and normetanephrine) on 24-h urine collection, as these levels are unaffected by pregnancy or pre-eclampsia. Definitive treatment of phaeochromocytoma is surgical and the laparoscopic approach has been shown to be safe and is preferred for most phaeochromocytomas. Medical preparation and treatment of hypertension is essential for safe surgery. Timing of adrenalectomy is either during the second trimester or as a staged procedure after Caesarean section delivery.

Adrenal Gland Neoplasms↗
PubMed2006

Do people with diabetes who need to talk want to talk?

AIM: Our objective was to determine whether people with diabetes who ask for psychological support are those who are experiencing clinically significant levels of psychological distress. METHOD: Three hundred people with diabetes were asked to complete psychometrically validated questionnaires that assessed subjective need and objective psychological distress. RESULTS: High levels of psychological distress were reported: 25% reported depressive symptomatology, 41% reported clinically significant levels of anxiety and 51% reported some binge eating behaviour. Participants also indicated a desire to talk to diabetes professionals about various problem areas in diabetes. Those reporting psychological distress, especially depression, were most likely to indicate a desire to talk to someone about living with diabetes. CONCLUSIONS: Those who want to talk are those who need to talk. Future service development issues should acknowledge the needs and expressed wishes of service users.

Adolescent↗
PubMed2005

Osteochondrosis and copper: histology of articular cartilage from foals out of copper supplemented and non-supplemented dams.

Copper (Cu) supplementation of dams in late gestation may be protective against articular cartilage abnormalities in foals. Articular cartilage was harvested from 22 Thoroughbred foals at 160 days of age, at sites predisposed to osteochondrosis (OC), and examined for evidence of early cartilage abnormalities and established dyschondroplastic (DCP) lesions to determine if there were any significant differences due to mare Cu supplementation by injection during late gestation, or foal liver Cu concentration. Cu supplemented mares received calcium Cu edetate injections in late gestation (250 mg at around 220, 248, 276 and 304 days gestation, then every two weeks until foaling). Foals were euthanased at 160 days of age and articular cartilage was harvested from four defined sites. Samples were examined for histological appearance of chondrocytes after staining with haematoxylin and eosin, and were also stained with toluidine blue to indicate proteoglycan content. Alkaline phosphatase (ALP) activity was detected by histochemistry, and histocytochemical techniques were used to determine the expression of cathepsin B. Cu supplementation of the dam, or liver Cu concentration of the foal at birth or 160 days of age had no statistically significant effect on the frequency of cartilage irregularities observed grossly, or abnormalities detected histologically at four defined sites. ALP expression was similar in all samples. Cathepsin B expression varied between sites, and was seen in chondrocyte clusters. The intensity of toludine blue staining varied between sites. Minor histological cartilage abnormalities were observed in cartilage from clinically normal animals. These abnormalities might be 'early' dyschondroplastic lesions, which could resolve or progress. The role of Cu in the development, resolution or progression of dyschondroplastic lesions is poorly understood.

Animal Feed↗
PubMed2005

The insulin-like growth factor system and colorectal cancer: clinical and experimental evidence.

OBJECTIVE: The aim of this review is to clarify the involvement of the insulin-like growth factor (IGF) system in the development of colorectal malignancy. MATERIALS AND METHODS: Medline searches were used to identify key articles relating the IGF system with the development of colorectal cancer. RESULTS: The IGF system has been linked to colorectal malignancy by a convergence of data from epidemiological, clinical and laboratory-based sources. CONCLUSION: Further work is needed to characterise the IGF system expression in the colon. Such clarification could lead to the identification of targets that can be manipulated for clinical advantage.

Biomarkers, Tumor↗
PubMed2005

A randomised controlled trial and cost-effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over. The SAFE study.

OBJECTIVES: To determine the most cost-effective method of screening for atrial fibrillation (AF) in the population aged 65 years and over, as well as its prevalence and incidence in this age group. Also to evaluate the relative cost-effectiveness of different methods of recording and interpreting the electrocardiogram (ECG) within a screening programme. DESIGN: Multicentred randomised controlled trial. Purposefully selected general practices were randomly allocated to 25 intervention practices and 25 control practices. SETTING: Fifty primary care centres across the West Midlands, UK. PARTICIPANTS: Patients aged 65 years and over. INTERVENTIONS: GPs and practice nurses in the intervention practices received education on the importance of AF detection and ECG interpretation. Patients in the intervention practices were randomly allocated to systematic (n = 5000) or opportunistic screening (n = 5000). Prospective identification of pre-existing risk factors for AF within the screened population enabled comparison between targeted screening of people at higher risk of AF and total population screening. MAIN OUTCOME MEASURES: AF detection rates in systematically screened and opportunistically screened populations in the intervention practices were compared with AF detection rate in 5000 patients in the control practices. The screening period was 12 months. RESULTS: Baseline prevalence of AF was 7.2%, with a higher prevalence in males (7.8%) and patients aged 75 years and over (10.3%). The control population demonstrated higher baseline prevalence (7.9%) than either the systematic (6.9%) or opportunistic (6.9%) intervention population. In the control population 47 new cases were detected (incidence 1.04% per year). In the opportunistic arm 243 patients without a baseline diagnosis of AF were found to have an irregular pulse, with 177 having an ECG, yielding 31 new cases (incidence 0.69% per year). A further 44 cases were detected outside the screening programme (overall incidence 1.64% per year). In the systematic arm 2357 patients had an ECG yielding 52 new cases (incidence 1.1% per year). Of these, 31 were detected by targeted screening and a further 21 by total population screening. A further 22 cases were detected outside the screening programme (overall incidence 1.62% per year). In terms of ECG interpretation, computerised decision support software (CDSS) gave a sensitivity of 87.3%, a specificity of 99.1% and a positive predictive value (PPV) of 89.5% compared with the gold standard (cardiologist reporting). GPs and practice nurses performed less well. The only difference in performance between intervention populations and controls was that practice nurses from the control arm performed less well than with intervention practice nurses on interpretation of limb-lead (PPV 38.8% versus 20.8%) and single-lead (PPV 37.7% versus 24.0%) ECGs. The within-trial economic evaluation results showed the lowest incremental cost to be for the opportunistic arm, with an incremental cost-effectiveness ratio of 337 pounds Sterling for each additional case detected compared to the control arm. Opportunistic screening dominated both more intensive screening strategies. Model-based analyses showed small differences in cost and quality-adjusted life-years for different methods and intensities of screening, but annual opportunistic screening resulted in the lowest number of ischaemic strokes and greatest proportion of cases of AF diagnosed. Probabilistic sensitivity results indicated that there was a probability of approximately 60% that screening from the age of 65 years was cost-effective in both men and women. CONCLUSIONS: The results of the study indicated that in terms of a screening programme for atrial fibrillation in patients 65 and over, the only strategy that improved on routine practice was opportunistic screening, model-based analyses indicated that there was a probability of approximately 60% of annual opportunistic screening being cost effective. It is suggested that the following topics are worthy of further investigation: the effect of the implementation of a screening programme for AF on the uptake and maintenance of anticoagulation in patients aged 65 years and over; an evaluation of the role of CDSS in the diagnosis of cardiac arrythmias; the best method for routinely detecting paroxysmal AF; ways of improving healthcare professionals' performance in ECG interpretation; development of a robust economic model to incorporate data on new therapeutic agents for use as thromboprophylactic agents for patients with AF, and an evaluation of the relative risk of stroke for patients with incident as opposed to prevalent AF.

Aged↗