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Biomedical subjects

G Gill

Publications and source records attributed to G Gill.

At least 19 recordsLinked to original sources
PubMed2007

Feasibility study on the MammoSite in early-stage breast cancer: initial experience.

The aims of this study were to evaluate the feasibility, practicality, efficacy and safety of the delivery of accelerated partial breast irradiation using the MammoSite for the boost phase. Six patients aged 53-69 years with stage T1N0, T2N0, Grade I-II invasive ductal carcinoma received 9-10 Gy prescribed at 1 cm from the MammoSite balloon surface in two fractions of 4.5-5 Gy 6 h apart. The MammoSite was inserted 20-37 days postoperatively. External beam radiation therapy to the whole breast commenced 1-5 days after accelerated partial breast irradiation. The maximum skin dose ranged from 3 to 9 Gy. The skin-cavity distance ranged from 7 to 19 mm. Local discomfort resolved as the scar healed spontaneously within 3-5 days. No Grade III or higher acute toxicity or local infection was recorded. The ease of insertion and accuracy of dosimetry makes the MammoSite suitable for use in properly selected women with early-stage breast cancer in a trial setting.

Aged↗
PubMed2006

Hyponatraemia as a risk factor for hospital mortality.

Hyponatraemia is a common abnormality in hospitalized patients, with about 15% having levels below the lower limit of the laboratory reference range. Accepted wisdom is that hyponatraemia is a marker of poor prognosis. However, a critical analysis of the literature reveals significant problems. Researchers have used various cut-off levels for plasma sodium, often concentrating on more severely hyponatraemic groups. Many studies were small, and most did not include control groups. Nevertheless, the literature available does suggest an excess mortality associated with hyponatraemia. Whether this is a direct adverse effect of low serum sodium levels, or if hyponatraemia is simply a marker for 'sicker' patients, is not known. It is also uncertain whether mortality is increased with more severe hyponatraemia, or whether active correction of hyponatraemia will improve outcome. These issues should be addressed by adequately-powered, prospective, suitably controlled studies.

Hospital Mortality↗
PubMed2006

Successful cardiovascular risk reduction in Type 2 diabetes by nurse-led care using an open clinical algorithm.

AIM: To implement a protocol-driven, nurse-led cardiovascular risk reduction clinic using an open clinical algorithm. The primary aim of the clinic was to optimize blood pressure (BP) control; secondary aims were to reduce modifiable cardiovascular risk factors. METHODS: We studied 110 people with Type 2 diabetes attending a diabetes out-patient centre at University Hospital Aintree, Liverpool. Patients taking one or more antihypertensive drugs were selected for referral to the nurse-led clinic if BP was > 140/85 mmHg; there was no age threshold. An open clinical algorithm was designed to direct the nurse on the use of antihypertensive, statin and aspirin therapy plus lifestyle advice and concordance. RESULTS: Thirty-one percent of patients attending for a first visit to the nurse-led clinic had BP within target when measured to British Hypertension Society standards out of the consultant clinic. Mean BP was 150/76 mmHg compared with 178/88 mmHg (P < 0.001). Subsequently, BP was reduced to 130/68 mmHg (P < 0.001), this reduction being sustained at review 9 months later (mean BP 133/67 mmHg), with 87 (79%) achieving BP <or= 140/85 mmHg. Treatment modalities were adjusted to reduce cardiovascular risk, including antihypertensive medication, lipid-lowering therapy and antiplatelet therapy. High-density lipoprotein-cholesterol improved from 1.2 +/- 0.5 mmol/l to 1.4 +/- 0.5 mmol/l (P = 0.004). The number of patients with microalbuminuria decreased from 41 (47%) to 25 (28%) (P = 0.02), with a fall in urinary albumin:creatinine ratio from 3.0 (1.3-7.9) to 1.8 (1.0-5.0) mg/mmol (P = 0.01). The number of smokers decreased from 22 (20%) to 14 (13%) (P = 0.01). Although not included as an intervention in the protocol, HbA1c improved to 8.1 +/- 1.6% from 8.7 +/- 1.6% (P < 0.001). CONCLUSION: A protocol-driven, nurse-led clinic using an open clinical algorithm can be used effectively to manage cardiovascular risk reduction in Type 2 diabetes.

Algorithms↗
PubMed2006

Investigation and management of severe hyponatraemia in a hospital setting.

AIMS: To evaluate the assessment and management of severe hyponatraemia in a large teaching hospital. METHODS: Inpatients with serum sodium <125 mmol/l were identified prospectively from a laboratory database over a six month period. Notes were examined and data extracted. Case notes were carefully reviewed retrospectively by a consultant endocrinologist with regard to accuracy of the diagnosis and the appropriateness of investigations and management. RESULTS: 104 patients with a serum sodium <125 mmol/l were identified. Mean (SD) age was 69 (14), 52% were female, mean hospital stay was 16 (12) days, and overall mortality 27%. Adequate investigations were rarely performed. Only 28 (26%) had plasma osmolality measured, 29 (27%) urine osmolality, 11 (10%) urinary sodium, 8 (8%) plasma cortisol, and 2 (2%) a short Synacthen test. Comparing the "ward" and "specialist review" diagnoses, there were significant discrepancies for "no cause found" (49% v 27%, p<0.001), alcohol (6% v 11% p<0.01), and syndrome of inappropriate antidiuresis (20% v 32%, p = 0.001). Treatment was often illogical with significant management errors in 33%. These included fluid restriction and intravenous saline given together (4%) and fluid restriction in diuretic induced hyponatraemia (6%). Mortality was higher in the group with management errors (41% v 20% p = 0.002). CONCLUSION: Severe hyponatraemia is a serious condition, but its investigation and evaluation is often inadequate. Some treatment patterns seem to be arbitrary and illogical, and are associated with higher mortality.

Adult↗
PubMed2005

Uteroplacental insufficiency affects epigenetic determinants of chromatin structure in brains of neonatal and juvenile IUGR rats.

Intrauterine growth retardation (IUGR) increases the risk of neuroendocrine reprogramming. In the rat, IUGR leads to persistent changes in cerebral mRNA levels. This suggests lasting alterations in IUGR cerebral transcriptional regulation, which may result from changes in chromatin structure. Candidate nutritional triggers for these changes include altered cerebral zinc and one-carbon metabolite levels. We hypothesized that IUGR affects cerebral chromatin structure in neonatal and postnatal rat brains. Rats were rendered IUGR by bilateral uterine artery ligation; controls (Con) underwent sham surgery. At day of life 0 (d0), we measured cerebral DNA methylation, histone acetylation, expression of chromatin-affecting enzymes, and cerebral levels of one-carbon metabolites and zinc. At day of life 21 (d21), we measured cerebral DNA methylation and histone acetylation, as well as the caloric content of Con and IUGR rat breast milk. At d0, IUGR significantly decreased genome-wide and CpG island methylation, as well as increased histone 3 lysine 9 (H3/K9) and histone 3 lysine 14 (H3/K14) acetylation in the hippocampus and periventricular white matter, respectively. IUGR also decreased expression of the chromatin-affecting enzymes DNA methyltransferase 1 (DNMT1), methyl-CpG binding protein 2 (MeCP2), and histone deacetylase (HDAC)1 in association with increased cerebral levels of zinc. In d21 female IUGR rats, cerebral CpG DNA methylation remained lower, whereas H3/K9 and H3/K14 hyperacetylation persisted in hippocampus and white matter, respectively. In d21 male rats, IUGR decreased acetylation of H3/K9 and H3/K14 in these respective regions compared with controls. Despite these differences, caloric, fat, and protein content were similar in breast milk from Con and IUGR dams. We conclude that IUGR results in postnatal changes in cerebral chromatin structure and that these changes are sex specific.

Acetylation↗
PubMed2005

Effect of a barley breakfast cereal on blood glucose and insulin response in normal and diabetic patients.

Prowashonupana (Prowash) is a shrunken-endosperm, short awn, waxy starch, hulless barley with low starch, high fiber, high protein, and a relatively high concentration of free sugars. The study was designed to compare equivalent breakfast meals (w/w) of Prowash and oatmeal for glycemic response in diabetic and non-diabetic subjects. A commercial liquid meal replacer (LMR) was included as a reference standard. A substantial reduction of the post-prandial glycemic peak following ingestion of Prowash was observed as compared to LMR or oatmeal. In the non-diabetic subjects, the maximal rise in glucose from baseline was 26.3 +/- 3.9 mg/dL after LMR, 41.3 +/- 3.9 mg/dL after oatmeal and 6.4 +/- 2.7 mg/dL after Prowash (p < 0.01). The maximal increase in glucose in the diabetic patients was 69.9 +/- 4.5 mg/dL after LMR, 80.8 +/- 8.8 mg/dL after oatmeal and 28.4 +/- 3.5 mg/dL after Prowash (p < 0.01). The maximal increase in insulin post-LMR was 33.9 +/- 3.6 mIU/ml in the diabetic patients and 54.0 +/- 9.8 mIU/ml in the non-diabetic controls. Oatmeal elicited a maximal insulin increase of 29.9 +/- 4.2 mIU/ml in the control subjects and 21.4 +/- 2.5 mIU/ml in the diabetic patients. In contrast, the maximal insulin increase after Prowash was 8.6 +/- 1.5 mIU/ml in the non-diabetic controls and 6.8 +/- 1.2 mIU/ml in the diabetic patients (p < 0.01).

Avena↗
PubMed2005

Improved glycaemic control--an unintended benefit of a nurse-led cardiovascular risk reduction clinic.

AIMS: One hundred and ten patients with Type 2 diabetes were referred into a nurse-led cardiovascular risk reduction clinic. The primary aim of the clinic was to optimize blood pressure (BP) control and address cardiovascular risk factors. METHODS: Those attending outpatient clinics were referred into a nurse-led cardiovascular risk reduction clinic if BP was above 140/85 mmHg. There was no intervention strategy designed in the nurse clinic protocol to improve glycaemic control. RESULTS: Following attendance at the clinic, there was a significant improvement in HbA1c noted when patients were reviewed 9 months later. HbA1c improved from 8.7 +/- 1.6 to 8.1% +/- 1.6% (P < 0.001) in the whole cohort. Further analysis showed that, after excluding those who had received intervention to improve glycaemic control from another source, during the same period there remained a significant improvement in the non-intervention group of patients. CONCLUSION: Frequent regular contact and health education in a nurse-led clinic to reduce cardiovascular risk may improve HbA1c in the absence of any specific intervention to improve glycaemic control.

Administration, Oral↗
PubMed2004

On the role of the starved codon and the takeoff site in ribosome bypassing in Escherichia coli.

Translating ribosomes can skip over stretches of messenger RNA and resume protein chain elongation after a "bypassed" region. We have previously shown that limitation for isoleucyl-tRNA can initiate a ribosome bypass when an AUA codon is in the ribosomal A-site. We have now generalized this effect to other "hungry" codons calling for four different limiting aminoacyl-tRNA species, suggesting that a pause at any A-site will have this effect. We have assessed bypassing in a large family of reporters with nearly every different triplet in the "takeoff site", i.e. the P-site on the 5' side of the hungry codon, and an identical "landing site" codon 16 nucleotides downstream. The different takeoff sites vary over a factor of 50 in bypassing proficiency. At least part of this variation appears to reflect stability of the codon Colon, two colons anticodon interaction at the takeoff site, as indicated by the following: (a) the bypassing proficiency of different tRNAs shows a rough correlation with the frequency of A Colon, two colons U as opposed to G Colon, two colons C pairs in the codon Colon, two colons anticodon association; (b) specific tRNAs bypass more frequently from codons ending in U than from their synonym ending in C; (c) an arginine tRNA with Inosine in the wobble position which reads CGU, CGC, and CGA bypasses much more frequently from the last codon than the first two synonyms.

Amino Acid Sequence↗
PubMed2004

Evidence for affluence-related hypertension in urban Brazil.

Cardiovascular diseases are a leading cause of mortality, and systemic hypertension is a major risk factor. There is an increasing prevalence of hypertension in urban areas of developing countries, due to lifestyle changes associated with economic transition and urbanisation. This study aimed to describe the prevalence and identify risk factors for hypertension in an urban area of South America (Coroa do Meio district in Aracaju, Sergipe State, north-east Brazil) and to examine intraurban hypertension prevalence differences. A cross-sectional survey of 400 adults aged 25 years and over was carried out. Information about health and lifestyle was obtained from a structured interview, followed by assessment of blood pressure (BP) and anthropometry. There were 31.8% (95% confidence interval 27.3-36.6%) participants with hypertension (defined as a systolic BP >140, diastolic BP >90 mmHg, or on antihypertensive medication). Hypertension was independently associated with older age, central obesity (greater waist-to-hip ratio), shorter height and residing in a high socio-economic residential area. Of the four neighbouring areas, hypertension prevalence was 52% in the area of highest income and education, compared with 19, 24 and 34% in the other three areas. The high prevalence of hypertension in this population, and the strong independent association with relative affluence, demonstrates the need for effective primary prevention of hypertension, targeted at modifiable risk factors.

Adult↗
PubMed2004

Thrombophlebitis diagnosed on indium-111 labelled white cell scan.

A 64-year-old lady with type 2 diabetes and a non-resolving right foot ulcer, had an indium-111 labelled white cell scan (indium-111 WCS) to investigate the possibility of underlying osteitis. The scan suggested the possibility of infective thrombophlebitis. Unknown to the clinical team who requested the scan and the radiologist who performed it, the lady was admitted to hospital 2 days following the procedure with cellulitis and septic thrombophlebitis in the right leg. There is only one previous report in the literature of septic thrombophlebitis being diagnosed in this way. Perhaps indium-111 WCS has something to offer in the diagnosis of this condition and in determining those who require antibiotic treatment.

Female↗
PubMed2003

Patients' perspectives on diabetes health care education.

Living with Type 2 diabetes requires that patients develop a range of competencies that allow them to take greater control over the treatment of their disease. This requires education that promotes health whilst respecting individuals' self-perceived needs and voluntary choices. Whilst such a concept is not new in the field of diabetes, health professionals are still struggling with how to administer it successfully. This paper presents the findings of a research trial of a theoretically constructed educational intervention. It focuses on the patients' perspectives of what they valued about the intervention which was found to be clinically effective over a short-term period only. Limitations to maintaining effects were associated with a number of factors. The study found that whilst patients can be educated toward greater autonomy, not all health professionals are ready to work in partnership with them. It highlighted the importance of clinical staff not only gaining a better understanding of diabetes management, but also of the theoretical principles underlying patient empowerment. This paper outlines these principles and shows how they were synthesized to produce a framework for informing practice. Patients' views are utilized to provide guidelines for improving the outcomes of patient education.

Adult↗
PubMed2002

Insulin-treated diabetes and driving in the UK.

Diabetes, and particularly insulin-treated diabetes, has important implications for motor vehicle driving, largely because of its association with potential hypoglycaemia. For this reason, most countries operate some driving restrictions on insulin-treated diabetic patients, as well as systems of intermittent reassessment of hypoglycaemic risk. In the UK, regulations are operated by the Driver and Vehicle Licensing Agency (DVLA), which is an agency of the Department of the Environment, Transport and the Regions (DETR). They are supported by an Expert Panel which advises the Secretary of State on diabetes-related issues relating to fitness to drive. The patient organization Diabetes UK is also concerned with diabetes and driving issues, largely from a position of lobbying policy-influencers and supporting individual cases. All parties involved with diabetes and driving issues recognize the need for more research on the subject, as the current literature is flawed in design, though no convincing excess of accidents amongst diabetic drivers has been conclusively demonstrated. Currently in the UK, Class 2 vehicles (large trucks and passenger vehicles) are barred to diabetic drivers on insulin. European law has recently extended this to so-called C1 (large vans and small lorries) and D1 (minibuses) vehicles, though the law has recently been revised to allow individual consideration for potential diabetic C1 drivers on insulin treatment. Diabetes and insulin-treated diabetes is an emotive and difficult issue, for which a stronger evidence base is urgently needed.

Automobile Driving↗
PubMed2002

Adverse pulmonary vascular effects of high dose tricyclic antidepressants: acute and chronic animal studies.

Overdose of tricyclic antidepressants, which inhibit cellular serotonin (5-HT) uptake, sometimes causes acute respiratory syndrome-like symptoms. Their acute and chronic cardiopulmonary actions, which might be implicated, utilising both in vivo and ex vivo animal studies, were investigated in this study. Acute amitriptyline (AMI), iprindole and imipramine caused dose-dependent prolonged rises in pulmonary artery pressure and oedema in anaesthetised cats in vivo. Acute AMI, in isolated ex vivo blood-perfused rat lungs, also caused dose-dependent sustained vasoconstriction, which could be attenuated with either calcium channel inhibition or a nitric oxide donor. It was demonstrated that the pressor effects of AMI were not due to release of histamine, serotonin, noradrenaline, or the activities of cycloxygenase or lipoxygenase. After AMI, hypoxic pulmonary vasoconstriction and the pressor actions of 5-HT and noradrenaline were diminished, possibly due to uptake inhibition. Activities of the endothelial-based enzymes, nitric oxide synthase and endothelin-converting enzyme, were undiminished. Large acute doses of AMI caused oedema with rupture of capillaries and alveolar epithelium. Chronic iprindole raised pulmonary artery pressure and right ventricle (RV)/left ventricle (LV) + septal (S) weight. Chronic AMI led to attenuation of the pressor action of 5-HT, especially when associated with chronic hypoxic-induced pulmonary hypertension. RV/LV+S weight increased, attributable to LV decline. The acute and chronic effects observed might have relevance to clinical overdose, while the attenuation of acute effects offers possible therapeutic options.

Acute Disease↗
PubMed2001

Regulation of cytokine-independent survival kinase (CISK) by the Phox homology domain and phosphoinositides.

PKB/Akt and serum and glucocorticoid-regulated kinase (SGK) family kinases are important downstream targets of phosphatidylinositol 3 (PI-3) kinase and have been shown to mediate a variety of cellular processes, including cell growth and survival. Although regulation of Akt can be achieved through several mechanisms, including its phosphoinositide-binding Pleckstrin homology (PH) domain, how SGK kinases are targeted and regulated remains to be elucidated. Unlike Akt, cytokine-independent survival kinase (CISK)/SGK3 contains a Phox homology (PX) domain. PX domains have been implicated in several cellular events involving membrane trafficking. However, their precise function remains unknown. We demonstrate here that the PX domain of CISK interacts with phosphatidylinositol (PtdIns)(3,5)P2, PtdIns(3,4,5)P3, and to a lesser extent PtdIns(4,5)P2. The CISK PX domain is required for targeting CISK to the endosomal compartment. Mutation in the PX domain that abolished its phospholipid binding ability not only disrupted CISK localization, but also resulted in a decrease in CISK activity in vivo. These results suggest that the PX domain regulates CISK localization and function through its direct interaction with phosphoinositides. Therefore, CISK and Akt have evolved to utilize different lipid binding domains to accomplish a similar mechanism of activation in response to PI-3 kinase signaling.

Amino Acid Sequence↗
PubMed2001

Fear and frustration--the Liverpool cholera riots of 1832.

Public mistrust in the medical profession is not new. We describe a series of street riots that took place in the city of Liverpool in north-west England in 1832 during a cholera epidemic. The disturbances were directed primarily against the local medical fraternity. The episode is of interest, since the same city recently experienced a similar crisis of confidence between doctors and public. On this occasion the cause was not cholera, but rather the reports from Alder Hey Children's Hospital that organ parts from deceased infants undergoing necropsy had been kept for several years without parental consent.

Attitude to Health↗
PubMed2001

Conserved regions of the Drosophila erect wing protein contribute both positively and negatively to transcriptional activity.

Genetic studies of the Drosophila erect wing (ewg) gene have revealed that ewg has an essential function in the embryonic nervous system and is required for the specification of certain muscle cells. We have found that EWG is a site-specific transcriptional activator, and we report here that evolutionarily conserved regions of EWG contribute both positively and negatively to transcriptional activity. Using gel mobility shift assays, we have shown that an EWG dimer binds specifically to DNA. In transfection assays, EWG activated expression of a reporter gene bearing specific binding sites. Analysis of deletion mutants and fusions of EWG to the Gal4 DNA binding domain has identified a transcriptional activation domain in the C terminus of EWG. Deletion analysis also revealed a novel inhibitory region in the N terminus of EWG. Strikingly, both the activation domain and the inhibitory region are conserved in EWG homologs including human nuclear respiratory factor 1 (NRF-1) and the sea urchin P3A2 protein. The strong conservation of elements that determine transcriptional activity suggests that the EWG, NRF-1, and P3A2 family of proteins shares common mechanisms of action and has maintained common functions across evolution.

Amino Acid Sequence↗