Biomedical subjects

D Holmes

Publications and source records attributed to D Holmes.

At least 19 recordsLinked to original sources

PubMed2006

Twelve-week monotherapy with the DPP-4 inhibitor vildagliptin improves glycemic control in subjects with type 2 diabetes.

UNLABELLED: Inhibition of dipeptidyl peptidase-4 enhances the activity of incretin hormones, improving glycemic control in subjects with type 2 diabetes. This twelve-week randomized, double-masked, placebo-controlled study assessed the efficacy and tolerability of the specific and potent oral dipeptidyl peptidase-4 inhibitor, vildagliptin (25 mg, bid, n=70) VS. placebo (bid, n=28) in previously diet-treated subjects with type 2 diabetes. Standardized meal tests were performed at baseline and endpoint. The between-group difference in adjusted mean change in HbA1c from baseline to endpoint was - 0.6 +/- 0.2 % (p=0.0012) for the whole cohort (baseline 8.0 %) and -1.2 % for subjects with baseline HbA1c 8.0 - 9.5 %. Fasting glucose and mean prandial glucose were reduced by 1.1 +/- 0.4 (p=0.0043) and 1.9 +/- 0.5 mmol/l (p <0.0001), respectively. The between-group differences in corrected insulin response at peak glucose and mean prandial C-peptide were + 0.06 +/- 0.02 (p=0.0258) and + 0.10 +/- 0.03 nmol/l (p=0.0031), respectively. Vildagliptin had no effect on fasting lipid levels or body weight. The incidence of adverse events was similar in subjects receiving placebo (71.4 %) and vildagliptin (55.7 %). CONCLUSION: monotherapy with vildagliptin is well tolerated and improves glycemic control in diet-treated subjects with type 2 diabetes. Concomitant improvements in beta-cell function were also observed. Subjects with higher baseline HbA1c levels showed greater response.

Adamantane↗

PubMed2005

Sperm banking in adolescent cancer patients.

BACKGROUND: Semen cryopreservation is a widely available method of maintaining fertility in male cancer patients. However this facility is not always used. AIMS: To identify the barriers to successful sperm banking in a group of adolescent and young adult patients. METHODS: Questionnaires were administered to 55 patients aged 13-21 years who had received potentially gonadotoxic therapy between 1997 and 2001 and had been offered sperm banking. RESULTS: Forty five questionnaires were completed; 67% of respondents were able to bank sperm. Those who had been unsuccessful were younger and described higher levels of anxiety at diagnosis and greater difficulty in talking about fertility. They also described less understanding of sperm banking at the time of diagnosis. CONCLUSION: Most adolescent cancer patients who have been offered fertility preservation are able to bank sperm. Younger patients may be helped by the provision of high quality information and more open discussion of the technique.

Adolescent↗

PubMed2005

Comparison of the efficacy of remote consultations and personal consultations for the treatment of dogs which are aggressive towards their owners.

Two groups of 42 dogs which were aggressive towards their owners were enrolled into a study designed to compare the efficacy of remote consultations with direct personal consultations for the treatment of the aggressive behaviour. The level of aggression of the dogs was assessed before and after programmes designed to modify their behaviour. Both programmes resulted in a significant reduction in the aggressive behaviour of the dogs towards their owners, and there was no significant difference between the effectiveness of the recommendations, whether they were made without having seen the dog or during a personal consultation with the dog and its owner.

Aggression↗

PubMed2005

On-chip high-speed sorting of micron-sized particles for high-throughput analysis.

A new design of particle sorting chip is presented. The device employs a dielectrophoretic gate that deflects particles into one of two microfluidic channels at high speed. The device operates by focussing particles into the central streamline of the main flow channel using dielectrophoretic focussing. At the sorting junction (T- or Y-junction) two sets of electrodes produce a small dielectrophoretic force that pushes the particle into one or other of the outlet channels, where they are carried under the pressure-driven fluid flow to the outlet. For a 40 microm wide and high channel, it is shown that 6 microm diameter particles can be deflected at a rate of 300/s. The principle of a fully automated sorting device is demonstrated by separating fluorescent from non-fluorescent latex beads.

Cell Separation↗

PubMed2005

Symptoms of psychological distress among older adults in Canadian long-term care centres.

Psychological distress can lead to negative consequences affecting the quality of life of older adults living in long-term care centres. The goal of this study was to determine the prevalence of symptoms of psychological distress and their associated factors among these residents. A cross-sectional descriptive study was conducted among 1999 long-term care residents aged 65 and over. Nine hundred and eleven persons (45.6%) displayed at least one symptom of psychological distress either at one time or more in the week preceding data collection, and 22.4% were identified as psychologically distressed. Multivariate analysis indicated that psychological distress was associated with disruptive behaviours and benzodiazepine use among women residents, and with insomnia in men residents. In conclusion, when clinicians screen for mental health disorders, they should take into consideration that symptoms of insomnia or disruptive behaviours may mask psychological distress.

Aged↗

PubMed2005

How place matters: unpacking technology and power in health and social care.

The devolution of care into nontraditional community-based settings has led to a proliferation of sites for health and social care. Despite recent (re)formulations of 'evidence-based' approaches that stress the importance of optimizing interventions to best practice by taking into account the uniqueness of place, there is relatively little guidance in the literature and few attempts to systematically 'unpack' key dimensions of settings most relevant to policy, practice and research. In this paper, we explore how place matters for health and social care. In effect, we propose making place the lens through which to view practice, and not simply an interesting sideline focus. We focus specifically on (a) the emplacement of power relations in health and social care in and across settings; and (b) the pervasive (and often unrecognised) influence of technology on and in place (both 'mundane' and more visible 'high' technologies) as arguably among the most significant and pervasive (and often overlooked) dimensions of place pertinent to health and social care in both traditional (institutional) and nontraditional (community) settings. Drawing on diverse disciplinary literatures, we seek to make visible certain issues and bodies of work that health professionals may not be aware of, and which often remain inaccessible to practitioners and applied researchers on account of their density, complexity, and specialised terminology. In particular, drawing on the rich tradition of cultural studies, we advance the culture of place as a rubric for understanding the complex interrelationship between power, technology, culture, and place. Several fruitful avenues for place-sensitive research of health and social care practice (and its effects) are suggested.

Benchmarking↗

PubMed2005

Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response.

OBJECTIVE: A novel treatment option for diabetic patients is the enhancement of incretin hormone activity by inhibition of the enzyme dipeptidyl peptidase-4 (DPP-4). This study was designed to establish a dose of the DPP-4-inhibitor vildagliptin (LAF237) that was effective in reducing HbA1c levels and was safe and well tolerated in patients with type 2 diabetes. PATIENTS AND METHODS: The study of 279 patients with type 2 diabetes consisted of a 4-week run-in phase where patients received placebo and a 12-week active treatment phase where they received one of the following dosages of vildagliptin: 25 mg twice daily, 25, 50 or 100 mg once daily (qd), or placebo. RESULTS: There was a statistically significant reduction in HbA1c levels in the vildagliptin 50 mg qd (p=0.003) and 100 mg qd groups (p=0.004) compared with the placebo group. The mean 4-h postprandial glucose level was significantly reduced from placebo in the vildagliptin 50 mg qd group (p = 0.012) and mean 4-h postprandial insulin was significantly increased from baseline vs. placebo in the vildagliptin 100 mg qd group (p=0.022). The assessment of beta-cell function (HOMA-B) was significantly increased in the vildagliptin 100 mg qd treatment group (p=0.007). The incidence of adverse events was similar in all treatment groups including placebo. CONCLUSIONS: Vildagliptin, at 50 and 100 mg qd, was effective in reducing HbA1c levels compared with placebo in patients with type 2 diabetes. Vildagliptin at dosages up to 100 mg qd appeared safe and well tolerated.

Adamantane↗

PubMed2004

Apparent redundancy of electron transfer pathways via bc(1) complexes and terminal oxidases in the extremophilic chemolithoautotrophic Acidithiobacillus ferrooxidans.

Acidithiobacillus ferrooxidans is an acidophilic chemolithoautotrophic bacterium that can grow in the presence of either the weak reductant Fe(2+), or reducing sulfur compounds that provide more energy for growth than Fe(2+). We have previously shown that the uphill electron transfer pathway between Fe(2+) and NAD(+) involved a bc(1) complex that functions only in the reverse direction [J. Bacteriol. 182, (2000) 3602]. In the present work, we demonstrate both the existence of a bc(1) complex functioning in the forward direction, expressed when the cells are grown on sulfur, and the presence of two terminal oxidases, a bd and a ba(3) type oxidase expressed more in sulfur than in iron-grown cells, besides the cytochrome aa(3) that was found to be expressed only in iron-grown cells. Sulfur-grown cells exhibit a branching point for electron flow at the level of the quinol pool leading on the one hand to a bd type oxidase, and on the other hand to a bc(1)-->ba(3) pathway. We have also demonstrated the presence in the genome of transcriptionally active genes potentially encoding the subunits of a bo(3) type oxidase. A scheme for the electron transfer chains has been established that shows the existence of multiple respiratory routes to a single electron acceptor O(2). Possible reasons for these apparently redundant pathways are discussed.

Acidithiobacillus↗

PubMed2004

Efficient replication by herpes simplex virus type 1 involves activation of the IkappaB kinase-IkappaB-p65 pathway.

Infection by herpes simplex virus type 1 (HSV-1) induces a persistent nuclear translocation of NFkappaB. To identify upstream effectors of NFkappaB and their effect on virus replication, we employed mouse embryo fibroblast (MEF)-derived cell lines with deletions of either IKK1 or IKK2, the catalytic subunits of the IkappaB kinase (IKK) complex. Infected MEFs were assayed for virus yield, loss of IkappaBalpha, nuclear translocation of p65, and NFkappaB DNA-binding activity. Absence of either IKK1 or IKK2 resulted in an 86 to 94% loss of virus yield compared to that of normal MEFs, little or no loss of IkappaBalpha, and greatly reduced NFkappaB nuclear translocation. Consistent with reduced virus yield, accumulation of the late proteins VP16 and gC was severely depressed. Infection of normal MEFs, Hep2, or A549 cells with an adenovirus vector expressing a dominant-negative (DN) IkappaBalpha, followed by superinfection with HSV, resulted in a 98% drop in virus yield. These results indicate that the IKK-IkappaB-p65 pathway activates NFkappaB after virus infection. Analysis of NFkappaB activation and virus replication in control and double-stranded RNA-activated protein kinase-null MEFs indicated that this kinase plays no role in the NFkappaB activation pathway. Finally, in cells where NFkappaB was blocked because of DNIkappaB expression, HSV failed to suppress two markers of apoptosis, cell surface Annexin V staining and PARP cleavage. These results support a model in which activation of NFkappaB promotes efficient replication by HSV, at least in part by suppressing a host innate response to virus infection.

Animals↗

PubMed2003

3D focusing of nanoparticles in microfluidic channels.

Dynamic focusing of particles can be used to centre particles in a fluid stream, ensuring the passage of the particles through a specified detection volume. This paper describes a method for focusing nanoparticles using dielectrophoresis. The method differs from other focusing methods in that it manipulates the particles and not the fluid. Experimental focusing is demonstrated for a range of different particle types, and discussed in terms of the operational limits of the device. Dynamic numerical simulations of the particle motion in the device are presented and compared with the experimental results. The potential of the device for nanoparticle control and manipulation in microfluidic chips is discussed.

Journal Article↗

PubMed2002

Outcomes of patients with chronic renal insufficiency in the bypass angioplasty revascularization investigation.

BACKGROUND: Although severe chronic kidney disease (CKD) is an independent predictor of mortality among patients with coronary artery disease, the impact of mild CKD on morbidity and mortality has not been fully defined. METHODS AND RESULTS: Morbidity and mortality for the 3608 patients with multivessel coronary artery disease enrolled in the Bypass Angioplasty Revascularization Investigation randomized trial and registry were compared on the basis of the presence and absence of CKD, defined as a preprocedure serum creatinine level of >1.5 mg/dL. Seventy-six patients had CKD. Patients with renal insufficiency were older and more likely to have a history of diabetes, hypertension, and other comorbidities. Among patients undergoing PTCA, patients with CKD had a greater frequency of in-hospital death and cardiogenic shock (P<0.05 and 0.01, respectively). There was a trend toward a larger proportion of patients with CKD experiencing angina at 5 years (P=0.079). Patients with CKD had more cardiac admissions (P=0.003 and <0.0001 for patients undergoing PTCA and CABG, respectively) and a shorter time to subsequent CABG after initial revascularization than patients without CKD (P=0.01). CKD was associated with a higher risk of death at 7 years, both of all causes (relative risk 2.2, P<0.001) and of cardiac causes (relative risk 2.8, P<0.001). CONCLUSIONS: CKD is associated with an increased risk of recurrent hospitalization, subsequent CABG, and mortality. This increased risk of death is independent of and additive to the risk associated with diabetes.

Angina Pectoris↗

PubMed2002

Dietary vitamin B12 deficiency in an adolescent white boy.

Dietary deficiency of cobalamin resulting in tissue deficiency in white individuals is unusual. However, several patients with dietary deficiency who were neither vegan nor Hindu have been described. This report describes the case of a 14 year old boy who was a white non-Hindu with a very low intake of cobalamin, which was not apparent until a detailed dietary assessment was performed. The patient responded rapidly to a combination of oral and parenteral B12. This case illustrates the fact that severe dietary vitamin B12 deficiency can occur in non-Hindu white individuals. Inadequate dietary content of B12 may not be apparent until a detailed dietary assessment is performed. This patient is likely to have had subclinical vitamin B12 deficiency for several years. Increased vitamin B12 requirements associated with the adolescent growth spurt may have provoked overt tissue deficiency.

Adolescent↗

PubMed2002

Design of a multiblock phantom for radiotherapy dosimetry applications.

This note describes the design of a multiblock semi-anatomic phantom, which lends itself to a variety of radiotherapy dosimetry applications, in particular, the audit of external beam treatment planning and delivery. The basic building blocks of the phantom were formed from a variety of tissue substitute materials and could be assembled in many ways to model different cross-sections through the body.

Equipment Design↗

PubMed2001

Titin and the sarcomere symmetry paradox.

Titin is thought to play a major role in myofibril assembly, elasticity and stability. A single molecule spans half the sarcomere and makes interactions with both a thick filament and the Z-line. In the unit cell structure of each half sarcomere there is one thick filament with 3-fold symmetry and two thin filaments with approximately 2-fold symmetry. The minimum number of titin molecules that could satisfy both these symmetries is 12. We determined the actual number of titin molecules in a unit cell from scanning transmission electron microscopy mass measurements of end-filaments. One of these emerges from each tip of the thick filament and is thought to be the in-register aggregate of the titin molecules associated with the filament. The mass per unit length of the end-filament (17.1 kDa/nm) is consistent with six titin molecules not 12. Thus the number of titin molecules present is insufficient to satisfy both symmetries. We suggest a novel solution to this paradox in which four of the six titin molecules interact with the two thin filaments in the unit cell, while the remaining two interact with the two thin filaments that enter the unit cell from the adjacent sarcomere. This arrangement would augment mechanical stability in the sarcomere.

Actin Cytoskeleton↗

PubMed2001

The dielectrophoretic levitation and separation of latex beads in microchips.

A linear travelling wave dielectrophoretic (twDEP) microchip was fabricated and used to investigate both the levitation and the twDEP motion of latex beads as a function of applied potential and frequency, suspending medium conductivity, bead size, and surface characteristics. The surface conductance of the latex beads was characterised by measurement of the dielectrophoretic (DEP) crossover frequency. Collection of sample prior to initiation of twDEP was achieved using positive DEP forces generated by an integrated pair of parallel electrodes positioned in front of the twDEP array within the microfluidic channel. The principle of linear twDEP separation is shown using latex beads and rabbit heart cells.

Algorithms↗

PubMed2001

Is the molecular composition of K(ATP) channels more complex than originally thought?

ATP-sensitive K+ (K(ATP)) channels are abundantly expressed in the heart and may be involved in the pathogenesis of myocardial ischemia. These channels are heteromultimeric, consisting of four pore-forming subunits (Kir6.1, Kir6.2) and four sulfonylurea receptor (SUR) subunits in an octameric assembly. Conventionally, the molecular composition of K(ATP) channels in cardiomyocytes and pancreatic beta -cells is thought to include the Kir6.2 subunit and either the SUR2A or SUR1 subunits, respectively. However, Kir6.1 mRNA is abundantly expressed in the heart, suggesting that Kir6.1 and Kir6.2 subunits may co-assemble to form functional heteromeric channel complexes. Here we provide two independent lines of evidence that heteromultimerization between Kir6.1 and Kir6.2 subunits is possible in the presence of SUR2A. We generated dominant negative Kir6 subunits by mutating the GFG residues in the channel pore to a series of alanine residues. The Kir6.1-AAA pore mutant subunit suppressed both wt-Kir6.1/SUR2A and wt-Kir6.2/SUR2A currents in transfected HEK293 cells. Similarly, the dominant negative action of Kir6.2-AAA does not discriminate between either of the wild-type subunits, suggesting an interaction between Kir6.1 and Kir6.2 subunits within the same channel complex. Biochemical data support this concept: immunoprecipitation with Kir6.1 antibodies also co-precipitates Kir6.2 subunits and conversely, immunoprecipitation with Kir6.2 antibodies co-precipitates Kir6.1 subunits. Collectively, our data provide direct electrophysiological and biochemical evidence for heteromultimeric assembly between Kir6.1 and Kir6.2. This paradigm has profound implications for understanding the properties of native K(ATP)channels in the heart and other tissues.

Adenosine Triphosphate↗

PubMed2001

Prevalence of depression and depression recognition in nursing homes.

BACKGROUND: The aim of this study was to estimate the prevalence of depression among nursing home residents, and the extent of depression recognition among nursing home staff. Random samples totaling 319 nursing home residents, drawn from a simple random sample of six downstate New York nursing homes were evaluated psychiatrically for depression. Samples of nurse aides, nurses and social workers also assessed the same residents for the presence of depressive symptomatology. METHOD: Psychiatrists assessed residents using the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria. Depression measures used were the Cornell Scale for Depression in Dementia, the Feeling Tone Questionnaire, the Hamilton Depression Rating and the Structured Clinical Interview for DSM-III-R Personality Disorders Scale. Nursing and social services staff assessed residents using Depression Recognition Measures. RESULTS: Based on psychiatric evaluation, the prevalence estimate for probable and/or definite major depressive disorder among testable subjects was 14.4% (95% CI of 10.6%-19.3%); 15.4% were not able to be assessed due to their refusal, impairment of consciousness, or severe physical illness. The estimate for minor depression was 16.8% (95% CI of 12.6%-21.9%). The prevalence of significant depressive symptomatology (including the category of possible depression) was 44.2% (95% CI of 38.2%-50.3%). The corresponding estimates of any depression were 19.7% for social workers, 29% for nurses and 32.1% for nurse aides. CONCLUSIONS: The prevalence of depressive disorders among nursing home residents is high; depression recognition is relatively low, with only 37%-45% of cases diagnosed by psychiatrists recognized as depressed by staff. A structured Depression Recognition Scale increased the rates of recognition (sensitivity of staff ratings) to 47%-55%, demonstrating the utility of the scale in increasing awareness of symptomatology.

Age Distribution↗

PubMed2001

From iron gaze to nursing care: mental health nursing in the era of panopticism.

The purpose of this paper is to question the utilization of mechanical devices (cameras and microphones) to ensure the surveillance of hospitalized patients on psychiatric wards. The works of French philosopher, Michel Foucault, and those of nursing theorist, Jean Watson, are used to support this analysis. A growing number of Canadian psychiatric health care institutions are using mechanical devices for surveillance. The security of staff and patients as well as therapeutic purposes are stated as rationale for these practices. However, a Foucauldian perspective leads us to think otherwise. The metaphor of the panopticon is then used to uncover another reality: a disciplinary one. Within the scope of this paper, the question of surveillance, disciplinary power, caring philosophy, and mental health nursing will be examined.

Facility Design and Construction↗