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Biomedical subjects

D Holmes

Publications and source records attributed to D Holmes.

At least 37 records · Page 2Linked to original sources
PubMed2001

Purification, crystallization and quaternary structure analysis of a glycerol dehydrogenase S305C mutant from Bacillus stearothermophilus.

Bacillus stearothermophilus glycerol dehydrogenase (GlyDH) is a 39.5 kDa molecular weight metalloenzyme which catalyzes the oxidation of glycerol to dihydroxyacetone with the concomitant reduction of NAD(+) to NADH. Despite its classification as a member of the 'iron-containing' polyol dehydrogenase family, studies on recombinant B. stearothermophilus GlyDH have shown this enzyme to be Zn(2+)-dependent. Crystals of a S305C GlyDH mutant were obtained by the hanging-drop vapour-diffusion method, using ammonium sulfate and PEG 400 as precipitating agents, in the presence and absence of NAD(+). The crystals belong to space group I422, with approximate unit-cell parameters a = b = 105, c = 149 A and one subunit in the asymmetric unit, corresponding to a packing density of 2.6 A(3) Da(-1). The crystals diffract X-rays to at least 1.8 A resolution on a synchrotron-radiation source. Determination of the structure will provide insights into the key determinations of catalytic activity of this class of enzymes, for which no structures are currently available.

Crystallization↗
PubMed2001

Forensic psychiatric nursing. Discursive practices and the emergence of a specialty.

1. While some authors argue that specialization is a threat to holistic nursing practice, others suggest that specialization is not only desirable and inevitable but should follow a rigorous process, including specific educational curriculum and examination procedures. 2. Two opposing views regarding forensic nursing are found in contemporary nursing literature. Some authors resist the discourse of specialization in nursing, while the discursive practices of others (e.g., leaders in forensic psychiatric nursing) could reflect a desire for power. 3. Using a poststructuralist approach, the controversy that has accompanied the development of forensic nursing through discursive practices is analyzed.

Clinical Competence↗
PubMed2000

Functional analysis of gapped microbial genomes: amino acid metabolism of Thiobacillus ferrooxidans.

A gapped genome sequence of the biomining bacterium Thiobacillus ferrooxidans strain ATCC23270 was assembled from sheared DNA fragments (3.2-times coverage) into 1,912 contigs. A total of 2,712 potential genes (ORFs) were identified in 2.6 Mbp (megabase pairs) of Thiobacillus genomic sequence. Of these genes, 2,159 could be assigned functions by using the WIT-Pro/EMP genome analysis system, most with a high degree of certainty. Nine hundred of the genes have been assigned roles in metabolic pathways, producing an overview of cellular biosynthesis, bioenergetics, and catabolism. Sequence similarities, relative gene positions on the chromosome, and metabolic reconstruction (placement of gene products in metabolic pathways) were all used to aid gene assignments and for development of a functional overview. Amino acid biosynthesis was chosen to demonstrate the analytical capabilities of this approach. Only 10 expected enzymatic activities, of the nearly 150 involved in the biosynthesis of all 20 amino acids, are currently unassigned in the Thiobacillus genome. This result compares favorably with 10 missing genes for amino acid biosynthesis in the complete Escherichia coli genome. Gapped genome analysis can therefore give a decent picture of the central metabolism of a microorganism, equivalent to that of a complete sequence, at significantly lower cost.

Amino Acids↗
PubMed2000

Image quality assessment in contemporary interventional cardiology laboratories: spatial and low-contrast video resolution.

Two measures of fluoroscopic image quality-high-contrast video spatial resolution and low-contrast video resolution-were assessed in 64 interventional cardiology catheterization laboratories. The results of high-contrast spatial resolution testing indicate variable levels of performance with median values of 1.5, 2.0, and 2.5 line pairs/mm at the three levels of magnification. The results of the low-contrast video resolution testing indicate clinically relevant limitations in performance. This was particularly true when testing was performed in a dynamic mode under simulated large patient conditions. Under these conditions, 50% of systems failed to detect a wire of diameter 0.017". In addition, limited system dynamic range was identified in a substantial fraction of laboratories and may contribute to these important variations in performance. Taken together, these findings serve to characterize overall system performance in the current era of interventional cardiology and reaffirm the continued need for image quality assessment programs.

Cardiac Catheterization↗
PubMed2000

The PRESTO (Prevention of restenosis with tranilast and its outcomes) protocol: a double-blind, placebo-controlled trial.

BACKGROUND: Tranilast is a unique drug in clinical development for the prevention of restenosis after percutaneous transluminal coronary revascularization (PTCR). Tranilast interferes with proliferation and migration of vascular medial smooth muscle cells induced by platelet-derived growth factor and transforming growth factor beta1. Collagen synthesis in vascular medial smooth muscle cells is inhibited by tranilast, which also inhibits the release or production of cyclooxygenase-2 and restores cytokine-induced nitric oxide production. These mechanisms may contribute to the reduction of angiographic restenosis after coronary intervention previously reported in clinical studies. METHODS: The primary objective of this multicenter study of 11,500 patients is to compare the composite clinical event rate of death, myocardial infarction, or the need for ischemia-driven target vessel revascularization of tranilast (300 and 450 mg twice daily) for 1 or 3 months with that of placebo in patients undergoing PTCR with or without stenting for single or multiple vessels over a 9-month period. The lesions can be de novo or restenotic. All revascularization procedures and the use of glycoprotein IIb/IIIa agents are permitted. The inclusion criteria are meant to allow an "all comer" approach for generalization of results to the broadest possible PTCR population. A subset population (n = 2000) will undergo 9-month follow-up angiography, 1000 of which will also undergo intravascular ultrasound (n = 1000). This study is the first tranilast trial to be conducted in a Western population to confirm the improved angiographic findings reported in Japanese patients and to determine if the clinical sequelae of restenosis are also reduced. CONCLUSION: This multicenter study is the largest restenosis trial planned to date. It will test whether tranilast, a drug with multiple actions aimed at affecting proliferation and migration of vascular smooth muscle cells, can reduce clinical, angiographic, and intravascular ultrasound assessments of restenosis.

Adolescent↗
PubMed2000

Quantification of the selective retention of palladium octabutoxynaphthalocyanine, a potential photothermal drug, in mouse tissues.

Palladium octabutoxynaphthalocyanine (PdNc(OBu)8) is a potential photothermal therapy (PTT) agent, absorbing strongly in the near-infrared region with no ability to induce photodynamic-type sensitisation (unlike many related napthalocyanines). We report here on the application of high pressure liquid chromatography (HPLC) with near-infrared absorption detection for the determination of the tissue accumulation and clearance of PdNc(OBu)8 in a tumour-bearing mouse model (Balb/c mice with EMT6 carcinoma tumour). Due to its insolubility in aqueous-based solvents, the drug was delivered intraperitoneally in a Cremophor-containing vehicle. Good selective accumulation of the drug into the tumour versus muscle or skin is observed, with the best combination of selectivity and tumour concentration occurring at 24-72 h after drug administration. Clearance times are quite long. Comparison with other similar drugs as reported in the literature indicates that the Cremophor-containing vehicle is likely in large part responsible for the observed pharmacokinetic behaviour. This drug shows potential for PTT and will be investigated further for therapy in this animal model.

Animals↗
PubMed2000

Towards a fibrous composite with dynamically controlled stiffness: lessons from echinoderms.

Sea urchins and sea cucumbers, like other echinoderms, control the tensile properties of their connective tissues by regulating stress transfer between collagen fibrils. The collagen fibrils are spindle-shaped and up to 1 mm long with a constant aspect ratio of approx. 2000. They are organized into a tissue by an elastomeric network of fibrillin microfibrils. Interactions between the fibrils are regulated by soluble macromolecules that are secreted by local, neurally controlled, effector cells. We are characterizing the non-linear viscoelastic properties of sea cucumber dermis under different conditions, as well as the structures, molecules and molecular interactions that determine its properties. In addition, we are developing reagents that will bind covalently to fibril surfaces and reversibly form cross-links with other reagents, resulting in a chemically controlled stress-transfer capacity. The information being developed will lead to the design and construction of a synthetic analogue composed of fibres in an elastomeric matrix that contains photo- or electro-sensitive reagents that reversibly form interfibrillar cross-links.

Animals↗
PubMed1999

Catheter-based reperfusion of unprotected left main stenosis during an acute myocardial infarction (the ULTIMA experience). Unprotected Left Main Trunk Intervention Multi-center Assessment.

The ULTIMA registry was a prospective, multicenter, international registry of 277 patients who underwent percutaneous coronary interventions of unprotected left main trunk stenosis. The 40 patients who underwent an emergency percutaneous left main intervention for acute myocardial infarction are the focus of this study. We compared the results of primary angioplasty with primary stenting, characterizing both the short-term (in-hospital) and long-term (12-month) outcomes. Of the 40 patients, 23 underwent primary angioplasty, whereas 17 underwent primary stenting. The angiographic success rate was an 88% for the cohort. The in-hospital death or coronary artery bypass grafting rate was 65% for the entire group, 74% for the percutaneous transluminal coronary angioplasty group (PTCA), and 53% for the stent group (p = 0.2). The in-hospital death rate was 55% for the entire cohort, 70% for the PTCA group, and 35% for the stent group (p = 0.1). The 12-month rate of death or bypass surgery was 83% and 58% for the PTCA and stent groups, respectively (p = 0.047). The 12-month survival rate was 35% and 53% for the PTCA and stent groups, respectively (p = 0.18). Bypass surgery was required in 6 patients in the PTCA group and 2 patients in the stent group (p = 0.07). Patients undergoing percutaneous interventions for unprotected left main myocardial stenosis during an acute myocardial infarction are critically ill; an initial percutaneous revascularization approach appears feasible and may be the preferred revascularization strategy. Primary stenting was associated with improved clinical outcomes.

Aged↗
PubMed1999

Identification and cloning of TWIK-originated similarity sequence (TOSS): a novel human 2-pore K+ channel principal subunit.

We have identified and cloned a new member of the mammalian tandem pore domain K+ channel subunit family, TWIK-originated similarity sequence, from a human testis cDNA library. The 939 bp open reading frame encodes a 313 amino acid polypeptide with a calculated Mr of 33.7 kDa. Despite the same predicted topology, there is a relatively low sequence homology between TWIK-originated similarity sequence and other members of the mammalian tandem pore domain K+ channel subunit family group. TWIK-originated similarity sequence shares a low (< 30%) identity with the other mammalian tandem pore domain K+ channel subunit family group members and the highest identity (34%) with TWIK-1 at the amino acid level. Similar low levels of sequence homology exist between all members of the mammalian tandem pore domain K+ channel subunit family. Potential glycosylation and consensus PKC sites are present. Northern analysis revealed species and tissue-specific expression patterns. Expression of TWIK-originated similarity sequence is restricted to human pancreas, placenta and heart, while in the mouse, TWIK-originated similarity sequence is expressed in the liver. No functional currents were observed in Xenopus laevis oocytes or HEK293T cells, suggesting that TWIK-originated similarity sequence may be targeted to locations other than the plasma membrane or that TWIK-originated similarity sequence may represent a novel regulatory mammalian tandem pore domain K+ channel subunit family subunit.

Amino Acid Sequence↗
PubMed1999

Effect of normobaric hyperoxia on two indexes of synaptic function in Fisher 344 rats.

The physiological response of two central nervous system neurotransmitter receptors to oxidative stress was studied using the rat model of hyperoxia. We show that hyperoxia leads to a decline in the ability of isoproterenol (ISO) to augment GABAergic responses in cerebellar Purkinje neurons in vivo. This effect is reversed by the N-tert-butylalpha-phenylnitrone (PBN). We also show that hyperoxia produces a decline in the ability of oxotremorine (OXO) to stimulate dopamine (DA) release in striatal slices. This effect is accompanied by an increase in hydroxyl radical levels in the CNS reflected in an increase in 2,3-DHBA, suggesting that the change is the result of an increased level of oxidative stress. We also show a time dependent effect of hyperoxia on both beta-adrenergic and muscarinic receptor function. We examined the interaction between age and hyperoxia exposure and found that in 12-month-old rats there is a decline in the baseline response prior to oxygen exposure that may interfere with observing a subsequent effect of hyperoxia. Differential effects were observed between the cerebellum and striatum with respect to the interaction of age and time of oxygen exposure. Overall, the data suggest that age and hyperoxia may be acting via a common mechanism because there was no synergistic effect of the two conditions.

Animals↗
PubMed1999

Foucault and nursing: a history of the present.

While a commitment to the development of nursing theory has been a significant force in nursing scholarship, particularly in the US, the authors have noted a recent trend among nurses in different countries to develop Foucauldian interpretations of nursing. The objective of this paper is to identify those publications by nurses that employ a Foucauldian perspective and to provide a useful summative review of these works to date, which illustrate the potential contribution of a Foucauldian reading of nursing. The authors have reviewed 27 publications written by nurses which present a Foucauldian analysis. These publications were issued between 1987 and 1998 in English, Portuguese and German. The most frequent concepts treated in the literature reviewed are power/knowledge, surveillance, discourse, discipline, resistance, docile bodies, clinical gaze, and panopticon. The literature reviewed illustrates that Foucault's concepts can have a profound impact on the way we conceive of nursing as a discipline and as a profession. Nursing care becomes a political event, nursing knowledge contributes to the dissemination of regimes of truth, and nurses, rather than being powerless, are perceived as professionals who exercise power over life in society. A Foucauldian reading of nursing enables nurses to move into a broader interdisciplinary and critical scholarship.

Diffusion of Innovation↗
PubMed1999

Who calls 999 and why? A survey of the emergency workload of the London Ambulance Service.

BACKGROUND: In 1996-97 there were 623,000 emergency (999) calls made to the London Ambulance Service (LAS) and this represents a 30% increase over the previous five years. The reasons for this increase, which is also observed nationally, remain unknown. It has been suggested that some callers may be using the 999 service "inappropriately" but no data are available from the ambulance service. OBJECTIVE: To describe the workload of the emergency ambulance service in London with specific reference to the nature and characteristics of 999 calls, to determine who dials 999 and why, and to establish the number and types of calls that could most appropriately be dealt with by other agencies. DESIGN: A one week census of all emergency calls responded to by the LAS. SETTING: Sixty eight LAS stations. METHODS: Collation of all routine LAS incident forms (LA4) including the classification of the crews' free text description of the incident. This was supplemented by a detailed workload questionnaire for 25% of calls. RESULTS: There were 10,921 calls responded to from 29 April to 5 May 1996. The census showed that the daily number of calls was highest on Saturday and lowest on Wednesday with about half being made during normal general practitioner (GP) working hours. Half of all calls were for women and one third were for people aged > or = 65. Accidents were the commonest type of incident (24%). The remainder comprised various medical conditions such as respiratory, cardiac, and obstetric problems. In 1.5% of calls there was no illness, injury, or assistance required and 5% were for "general assistance" and mostly concerned people aged > or = 65. The workload survey indicated that two thirds of incidents occurred at home and 70% of callers had not tried to contact a GP before dialing 999. In the professional opinion of the responding crew, 60% of calls required a 999 response, with the remainder thought more appropriately dealt with by other services such as primary care, psychiatric services, and social services. CONCLUSIONS: This study suggests that while the majority of 999 calls were "appropriate", part of the 999 workload could be dealt with by other services. More research is required to clarify why people contact the 999 service for non-emergency incidents and also to establish the views of GPs and other agencies as to the role and function of the IAS.

Emergency Medical Service Communication Systems↗
PubMed1999

Use of latent class analyses for the estimation of prevalence of cognitive impairment, and signs of stroke and Parkinson's disease among African-American elderly of central Harlem: results of the Harlem Aging Project.

A probability sample (response rate of 79.4%) of 164 African-American elderly residing in central Harlem was assessed using several standard cognitive screening measures and scales measuring stroke and Parkinson's symptoms, respectively. Both traditional cutting scores and the methods of latent class analysis were used to estimate point prevalence. The latent class prevalence ratio estimates range from 10 to 14%. The confidence intervals for cognitive impairment ranged from 5 to 18% with an average estimate of 12%. The latent class estimate for stroke effects was 11% and for two measures of neurological signs associated with Parkinson's disease 7 and 12%. About 2-3% of the sample were communication disordered, and 5% had significant ambulation disorder. These results indicate that a relatively large proportion of elderly community residents of central Harlem evidenced or reported health problems, any or all of which may constitute a public health challenge.

Black or African American↗