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Biomedical subjects

M Manning

Publications and source records attributed to M Manning.

At least 19 recordsLinked to original sources
PubMed2007

[Metabolic syndrome and erectile dysfunction. Epidemiologic associations and pathogenetic links].

There is abundant evidence for the association between erectile dysfunction (ED) and the traditional atherosclerotic risk factors, such as dyslipidemia, hypertension, glucose intolerance, and obesity, that make up the metabolic syndrome. Recent findings have demonstrated a linear relationship between the number of these risk factors and the prevalence of ED. There is also growing evidence that endothelial dysfunction characterized by decreased bioavailability of nitrogen monoxide (NO) and a proinflammatory, prothrombotic, and proliferative phenotype is the common pathogenetic pathway linking ED to peripheral vascular diseases. Since ED often occurs several years before any clinical manifestation of systemic cardiovascular disease, ED should be seen as a warning of early atherosclerotic disease and an opportunity for doctor and patient to initiate preventive measures.

Atherosclerosis↗
PubMed2006

The effect of sodium chloride on the dissolution of calcium silicate hydrate gels.

The use of cement based materials will be widespread in the long-term management of radioactive materials in the United Kingdom. One of the applications could be the Nirex reference vault backfill (NRVB) as an engineered barrier within a deep geological repository. NRVB confers alkaline conditions, which would provide a robust chemical barrier through the control of the solubility of some key radionuclides, enhanced sorption and minimised corrosion of steel containers. An understanding of the dissolution of C-S-H gels in cement under the appropriate conditions (e.g., saline groundwaters) is necessary to demonstrate the expected evolution of the chemistry over time and to provide sufficient cement to buffer the porewater conditions for the required time. A programme of experimental work has been undertaken to investigate C-S-H gel dissolution behaviour in sodium chloride solutions and the effect of calcium/silicon ratio (C/S), temperature and cation type on this behaviour. Reductions in calcium concentration and pH values were observed with samples equilibrated at 45 degrees C compared to those prepared at 25 degrees C. The effect of salt cation type on salt-concentration dependence of the dissolution of C-S-H gels was investigated by the addition of lithium or potassium chloride in place of sodium chloride for gels with a C/S of 1.0 and 1.8. With a C/S of 1.0, similar increases in dissolved calcium concentration with increasing ionic strength were recorded for the different salts. However, at a C/S of 1.8, anomalously high calcium concentrations were observed in the presence of lithium.

Calcium Compounds↗
PubMed2006

Strategies to improve the performance of learners in a nursing college. Part I: Issues pertaining to nursing education.

The aim of this contextual, exploratory, descriptive and qualitative study was to describe strategies to improve the performance of learners in a nursing college. The article seeks to deal with factors relating to nursing education that contribute to the poor performance of learners and to outline related strategies to improve the situation. Three focus group interviews were conducted. One group was formed by seven tutors, and the other two groups were formed by fourth-year learners following a four-year comprehensive diploma course. All participants voluntarily took part in the study. Data was analyzed using the descriptive method of open coding by Tesch (in Creswell, 1994:154-156). Trustworthiness was ensured in accordance with Lincoln and Guba's (1985:290-326) principles of credibility, conformability, transferability and dependability. The findings were categorized into issues pertaining to nursing education as follows: curriculum overload; lack of theory and practice integration; teaching and assessment methods that do not promote critical thinking; tutors' lack of skills and experience; inadequate preparation of tutors for lectures; insufficient knowledge of tutors regarding outcomes-based education approach to teaching and learning; inadequate process of remedial teaching; discrepancies between tutors' marking; lack of clinical role-models and high expectations from the affiliated university as regards standards of nursing development programme by the staff development committee of the nursing college under study for implementation. Future research should focus on the effectiveness of the described strategies to improve the learners' performance. It is also recommended that similar studies be conducted or replicated in other nursing colleges to address the problem of poor performance of learners engaged in a four-year comprehensive diploma course.

Curriculum↗
PubMed2006

Strategies to improve the performance of learners in a nursing college. Part II: Issues pertaining to management, attitudes and values.

UNLABELLED: This article forms part two of a bigger study that was conducted in a nursing college to explore and describe the reasons for the poor performance of learners. Part one of the study dealt with the issues pertaining to education, while this article (part two) seeks to describe issues pertaining to management, attitudes and values that lead to the poor performance of learners in the nursing college under study. A qualitative, exploratory and descriptive design that was contextual in nature was employed, and three focus groups interviews were conducted. Seven tutors formed one group while other two groups were formed by fourth-year learners following a comprehensive diploma course. All participants voluntarily participated in the study. Data was analyzed using the descriptive method of open coding in accordance with Tesch's protocol (in Creswell, 1994:154-156). Trustworthiness was ensured using the following principles: credibility, conformability, transferability and dependability (Lincoln & Guba 1985:290-326). Findings were categorized into issues pertaining to management, attitudes and values that had an influence on the poor performance of learners as follows: MANAGEMENT: Inadequate resources and study facilities; policies that change frequently; tutors' dissatisfaction with regard to staff development, the lack of involvement by management and lack of management support, staff shortage and maldistribution of staff members; ineffective selection process of learners; inconsistent regulations, and too many of them; policies and procedures resulting in confusion and poor discipline. Attitudes and values: Tutors' lack of motivation and interest, lack of respect by learners and no team work among tutors. Through a conceptualization process and the recommendations by participants, strategies to improve the learners' performance were described. It is recommended that these strategies be submitted to the staff development committee for implementation and future follow-up research be undertaken to determine the effectiveness of the strategies. It is also recommended that other nursing colleges replicate the study within their context.

Attitude↗
PubMed2005

Dual polarisation interferometry characterisation of DNA immobilisation and hybridisation detection on a silanised support.

Dual polarisation interferometry is an analytical technique that allows the simultaneous determination of thickness, density and mass of a biological layer on a sensing waveguide surface in real time. We evaluated, for the first time, the ability of this technique to characterise the covalent immobilisation of single stranded probe DNA and the selective detection of target DNA hybridisation on a silanised support. Two immobilisation strategies have been evaluated: direct attachment of the probe molecule and a more complex chemistry employing a 1,2 homobifunctional crosslinker molecule. With this technique we demonstrate it was possible to determine probe orientation and measure probe coverage at different stages of the immobilisation process in real time and in a single experiment. In addition, by measuring simultaneously changes in thickness and density of the probe layer upon hybridisation of target DNA, it was possible to directly elucidate the impact that probe mobility had on hybridisation efficiency. Direct covalent attachment of an amine modified 19 mer resulted in a thickness change of 0.68 nm that was consistent with multipoint attachment of the probe molecule to the surface. Blocking with BSA formed a dense layer of protein molecules that absorbed between the probe molecules on the surface. The observed hybridisation efficiency to target DNA was approximately 35%. No further significant reorientation of the probe molecule occurred upon hybridisation. The initial thickness of the probe layer upon attachment to the crosslinker molecule was 0.5 nm. Significant reorientation of the probe molecule surface normal occurred upon hybridisation to target DNA. This indicated that the probe molecule had greater mobility to hybridise to target DNA. The observed hybridisation efficiency for target DNA was approximately 85%. The results show that a probe molecule attached to the surface via a crosslinker group is better able to hybridise to target DNA due to its greater mobility.

Biosensing Techniques↗
PubMed2005

Highly optimized tolerance and power laws in dense and sparse resource regimes.

Power law cumulative frequency (P) versus event size (l) distributions P > or =l) approximately l(-alpha) are frequently cited as evidence for complexity and serve as a starting point for linking theoretical models and mechanisms with observed data. Systems exhibiting this behavior present fundamental mathematical challenges in probability and statistics. The broad span of length and time scales associated with heavy tailed processes often require special sensitivity to distinctions between discrete and continuous phenomena. A discrete highly optimized tolerance (HOT) model, referred to as the probability, loss, resource (PLR) model, gives the exponent alpha=1/d as a function of the dimension d of the underlying substrate in the sparse resource regime. This agrees well with data for wildfires, web file sizes, and electric power outages. However, another HOT model, based on a continuous (dense) distribution of resources, predicts alpha=1+1/d . In this paper we describe and analyze a third model, the cuts model, which exhibits both behaviors but in different regimes. We use the cuts model to show all three models agree in the dense resource limit. In the sparse resource regime, the continuum model breaks down, but in this case, the cuts and PLR models are described by the same exponent.

Journal Article↗
PubMed2004

[Pharmaceutical treatment of stress incontinence. New approaches via a direct effect of duloxetine on Onuf's nucleus].

Urinary continence and voiding are complex physiological processes and require the coordination of all three efferent areas of the nervous system (parasympathetic, sympathetic, somatic). The pudendal nerve contains efferent as well as afferent fibers, the former ones having their origin in Onuf's nucleus. A number of studies see a link in the central modulation of lower urinary tract activity through 5-HT and NE receptor agonists as well as antagonists. Previous information about the modulation of the lower urinary tract in humans has been obtained from animal experiments. Duloxetin, a combined serotonin/norepinephrine reuptake inhibitor may prove to be a new therapeutic agent for stress urinary incontinence. Duloxetin appears to act at the presynaptic neuron of Onuf's nucleus. A phase II and three phase III studies have shown significant and clinically relevant improvement in several parameters in comparison to placebo control. The most frequent adverse event observed was nausea.

Animals↗
PubMed2004

Head imaging abnormalities in dihydropyrimidine dehydrogenase deficiency.

Dihydropyrimidine dehydrogenase (DPD) deficiency is a rare autosomal recessive disorder of pyrimidine metabolism. Patients may present with a wide range of neurological symptoms during the first years of life. Head imaging abnormalities have been reported only rarely and include diffuse cerebral atrophy and white-matter hyperintensity. The pathogenesis of the white-matter abnormalities is unknown, although environmental factors and altered energy metabolism may be involved. To further understanding of the spectrum of brain abnormalities associated with DPD deficiency, we report a 17-month-old girl, born to a consanguineous Pakistani couple, who had a history of encephalopathy, prolonged hypoventilation, developmental delay and failure to thrive. Head MRI showed prominent sulci and abnormal T2 prolongation in the cerebral white matter and brainstem. Thus, DPD deficiency may feature prominent brain abnormalities involving the cerebral white matter and brainstem. Anoxic stress may have contributed to the clinical presentation and brain findings in this case. In order to define more clearly the contribution of DPD deficiency to the pathogenesis of these MRI abnormalities, we recommend performing detailed analysis of urine pyrimidine metabolites in patients who have such findings.

Brain↗
PubMed2004

The discovery of novel vasopressin V1b receptor ligands for pharmacological, functional and structural investigations.

Until recently, pharmacological studies dealing with vasopressin receptor isoforms were severely hampered by the lack of selective agonists or antagonists that recognize the pituitary V(1b) vasopressin receptor. By contrast, many selective vasopressin-related compounds are available for characterization of the vasopressor (V(1a)) or antidiuretic (V(2)) vasopressin receptor subtypes. Recently, SSR149415, a selective nonpeptide molecule, was discovered with nanomolar affinity for mammalian V(1b) receptors and good selectivity for the other vasopressin and oxytocin receptor isoforms. This molecule exhibits potent antagonist properties both in vitro and in vivo. We also designed synthetic peptides derived from [deaminocysteine(1),arginine(8)]vasopressin (dAVP), modified in position 4 by various amino acid residues. Some of these, d[cyclohexylalanine(4)]AVP or d[lysine(4)]AVP, have a high affinity and an excellent selectivity for the human V(1b) receptor subtype. However, they exhibit a mixed V(1b)/V(2) pharmacological profile for the rat vasopressin receptor isoforms. Whatever the species considered, these peptides behave as agonists both in bioassays performed in vitro and in vivo. The d[cyclohexylalanine(4)]AVP was tritiated and represents the first selective radiolabelled ligand available for studying the human V(1b) receptors. The discovery of these new selective V(1b) agonists and V(1b) antagonist allows an accurate pharmacological characterization of all the vasopressin receptor isoforms. As emphasized in this review, attention to the vasopressin and oxytocin receptor species differences is of critical importance in studies with all vasopressin and oxytocin ligands.

Animals↗
PubMed2003

Improved radiotracing of oxytocin receptor-expressing tumours using the new [111In]-DOTA-Lys8-deamino-vasotocin analogue.

Oxytocin receptors (OTR) have been described in a number of tumours of different origin, and represent a new target for specific radiolabelled oxytocin (OT) analogues in cancer diagnosis and therapy. By linking the DOTA chelating agent to position 8 of the deamino derivative of Lys(8)-vasotocin (dLVT), we obtained a new compound (DOTA-dLVT) with the following characteristics: (1) it forms a monomeric and stable compound that binds to OTR with an affinity comparable to that of the endogenous OT ligand; (2) it is characterised by a very good selectivity profile for the human OTR, with a low affinity binding to the closely related V1a, V1b and V2 vasopressin receptor subtypes; (3) it induces rapid and persistent receptor internalisation and (4) when radiolabelled, [(111)In]-DOTA-dLVT is efficiently and selectively taken up by OTR-positive tumours grown in mice. These features makes radiolabelled DOTA-dLVT a very good candidate for the radiotargeting of OTR-expressing tumours.

Animals↗
PubMed2003

Spontaneous tumescence after implantation of three-piece hydraulic penile prostheses: a short-term experience.

We evaluated spontaneous tumescence after penile prostheses implantation in a retrospective study. A total of 32 patients with three-piece hydraulic implants (17 Mentor Alpha I, 15 AMS Ultrex Plus) were enrolled. Consultation, personal interviews and questionnaires for both the patients and their partners provided the necessary information. The average follow-up period was 29 months. In total, 50 % of the patients reported spontaneous tumescence without activation of the implant and one further patient (3%) claimed full rigid spontaneous erections. General satisfaction with the prosthetic result was high at 91%. The following complications arose: one case of prosthesis infection, one case of mechanical failure, one case of cylinder dislocation and two cases of paraphimosis. A possible explanation for spontaneous tumescence after penile prosthesis implantation is the elevated preload of the compressed rather than destructed cavernous tissue. The artificial erection evoked by the prosthesis then takes the form of a normal physiological reaction and/or a good objective ridigity, and could account for the high patient satisfaction rate with three-piece hydraulic implants.

Adult↗
PubMed2002

Dissolution and partitioning behavior of hydrophobic ion-paired compounds.

PURPOSE: This study was conducted to determine the effects of counterion hydrophobicity on organic/aqueous partition coefficients for hydrophobic ion paired (HIP) complexes. Furthermore, the coupled dissolution and reverse ion-exchange kinetics for dissolution of HIP complexes into aqueous electrolyte solutions were measured and mathematically modeled. METHODS: HIP complexes of model drugs tacrine and l-phenylephrine were formed using linear sodium alkylsulfates and bis (2-ethylhexyl sodium sulfosuccinate). Equilibrium partition coefficients between chloroform and aqueous solutions for the complexes and the kinetics of dissolution of the complexes in buffered aqueous solutions were measured. RESULTS: The chloroform/aqueous partition coefficients for l-phenylephrine/bis (2-ethylhexyl sodium sulfosuccinate) complexes decrease with increasing molar surface tension increment of salts added to the aqueous solution. The logarithm of the partition coefficient for a homologous series of alkyl sulfate complexes decreases as the hydrophilic-lipophilic balance number increases. Dissolution of HIP complexes in deionized water shows first order kinetics, whereas dissolution in aqueous electrolyte solutions shows biphasic kinetics. A kinetic model explains these dissolution rates. CONCLUSIONS: Solubility and dissolution rates for HIP complexes depend on the hydrophobic-lipophilic balance number of the organic counter ion as well as on the electrolyte composition of aqueous solutions. Reverse ion-exchange kinetics are sufficiently slow to allow HIP complexes to be considered simple prodrugs.

Hydrophobic and Hydrophilic Interactions↗
PubMed2002

Intracavernous administration of SIN-1+VIP in an in vivo rabbit model for erectile function.

In accordance with the data reporting the identification of nitric oxide synthase (NOS) and vasoactive intestinal polypeptide (VIP) positive nerve fibres in the trabecular meshwork of the corpus cavernosum, we suggest that nitric oxide (NO) and VIP may serve complementary physiological roles in penile erection. Therefore SIN-1 and VIP were administered alone and in combination in an in vivo rabbit model. All rabbits revealed basal pressure values of 5-8 cm H2O intracavernously. In the rabbits intracavernously (i.c.) injected with SIN-1 alone and VIP alone, no adequate erectile responses were observed. Whereas, in the group intracavernously injected with the combination of SIN-1+VIP, erectile responses with mean maximal intracavernous pressure (max. ICP) 52.8 (+/-13.2) cm H2O were noted. These pressure elevations do not statistically diverge (P>0.05) than the ones obtained in the control group administered i.c. injections of the combination of papaverine/phentolamine (mean max. ICP 51 (+/-14.73) cm H2O). Referring to our results, we conclude that the combined use of SIN-1+VIP could play an important role in the physiological treatment of erectile dysfunction.

Animals↗
PubMed2002

Long-term results of Essed-Schroeder plication by the use of non-absorbable Goretex sutures for correcting congenital penile curvature.

This study evaluated the long-term outcome of the Essed-Schroeder procedure for correcting congenital penile curvature using non-absorbable Goretex sutures. The Essed-Schroeder procedure was performed in 35 patients with congenital ventral penile curvature (minimum 30 degrees ). Follow-up included a standardized interview with measurement of angulation. Twenty-three of 35 patients were available for complete long-term follow-up (average 34.3 months). The mean preoperative ventral curvature was 54 degrees. In 17/23 patients, the penis remained straightened. Recurrent curvature (average 23 degrees ) was observed in six of 23 patients. Fifteen of 23 patients complained of penile shortening (average 1.8 cm). Two of 23 patients reported disturbing side effects that were caused by plication nodes. In most cases, the results of penile straightening by the Essed-Schroeder procedure are excellent with a high grade of subjective satisfaction. Regarding the main problem, that is recurrent curvature, there is no decisive advantage of applying Goretex sutures. Discomfort caused by plication nodes can be reduced to a minimum by using a combination of soft Goretex sutures with the 'inverting stitch-technique'.

Adolescent↗
PubMed2002

[1-deamino-4-cyclohexylalanine] arginine vasopressin: a potent and specific agonist for vasopressin V1b receptors.

To date, there are no vasopressin (VP) agonists that exhibit a high affinity and selectivity for the VP V1b receptor with respect to the V1a, V2, and oxytocin receptors. In this study, we describe the synthesis and pharmacological properties of [1-deamino-4-cyclohexylalanine] arginine vasopressin (d[Cha4]AVP). Binding experiments performed on various membrane preparations revealed that d[Cha(4)]AVP exhibits a nanomolar affinity for V1b receptors from various mammalian species (rat, bovine, human). It exhibits high V1b/V1a and V1b/oxytocin selectivity for rat, human, and bovine receptors. Furthermore, it exhibits high V1b/V2 specificity for both bovine and human vasopressin receptors. Functional studies performed on biological models that naturally express V1b receptors indicate that d[Cha4]AVP is an agonist. Like VP, it stimulated basal and corticotropin-releasing factor-stimulated ACTH secretion and basal catecholamine release from rat anterior pituitary and bovine chromaffin cells, respectively. In vivo experiments performed in rat revealed that d[Cha4]AVP was able to stimulate both ACTH and corticosterone secretion and exhibits negligible vasopressor activity. It retains about 30% of the antidiuretic activity of VP. This long-sought selective VP V1b receptor ligand with nanomolar affinity will allow a better understanding of V1b-mediated VP physiological effects and is a promising new tool for V1b receptor structure-function studies.

Adrenocorticotropic Hormone↗
PubMed2001

Novel selective hypotensive vasopressin peptides: cardiovascular and structure-activity-relationship studies.

Recently, we discovered a series of peripheral acting selective hypotensive vasopressin peptides. Whether these peptides may interact with receptors outside the vasopressin receptor family and affect cardiac function could not be excluded. Accordingly, we tested the effects of these hypotensive vasopressin peptides on blood pressure and heart rate in intact rats and on the heart rate, ventricular contractile force and coronary flow of isolated perfused rat hearts. We found that the hypotensive vasopressin peptides did not modify cardiac function, either in vivo or in vitro. The vasodepressor potency was reduced when assayed in rats with vasopressin-maintained baseline blood pressure, suggesting that vasopressin and the hypotensive peptide compete for a common vasodilating vasopressin receptor in the vasculature. We have now synthesized more potent and radioiodinatable hypotensive peptides that could serve as lead compounds for the development of a radiomarker for the putative vasodilating vasopressin receptor.

Animals↗