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Biomedical subjects

P Moran

Publications and source records attributed to P Moran.

At least 19 recordsLinked to original sources
PubMed2007

Preliminary work on the development of a novel detection method for osteoporosis.

Osteoporosis affects both the organic and mineral phases of bone resulting in a decrease in resistance to fracture. Dual x-ray absorptiometry (DEXA) scans are used for diagnosing osteoporosis, which is conventionally characterised by a decrease in mineral density. Unfortunately, some patients who suffer osteoporotic fractures have normal bone density, because both the organic and the mineral phase are affected. However, there are currently no methods of evaluating the health of the organic phase. Patients undergoing treatment for osteoporosis have reported hardening of their fingernails. As the properties of nail and bone may be linked in a comparable, measurable way, this work used both mechanical (nano-indentation) and chemical (Raman spectroscopy) methods to evaluate differences between fingernails sourced from osteoporotic and non-osteoporotic patients. The difference in mean modulus between the nails sourced from the groups was 1.1 GPa. The disulphide bond content of fingernail samples from each group was measured by Raman spectroscopy and disulphide bond content of fingernail was found to be significantly lower in the osteoporotic group. It can be concluded that a relationship between the mechanical and chemical properties of nail and bone may exist in a measurable way. This work has suggested that changes in the organic phase of bone are reflected in similar proteins, such as keratin, from which fingernails are composed. Collagen and keratin are two distinct structural proteins, but they share the need for protein sulphation and disulphide bond formation, via cysteine, for their structural integrity. A disorder of either process should lead to disordered collagen and keratin synthesis.

Bone Density↗
PubMed2006

Laparoscopic versus open Burch colposuspension: a randomised controlled trial.

OBJECTIVE: To compare perioperative characteristics, short-term, and long-term outcomes for laparoscopic Burch colposuspension (LBC) and open Burch colposuspension (OBC) for the treatment of urinary stress incontinence. DESIGN: Randomised surgical trial with single blinding. SETTING: Three tertiary level teaching hospitals involving seven surgeons of varying skill levels. POPULATION: Two hundred women with urodynamic stress incontinence (USI). METHODS: The two groups were treated in identical fashion, except for the laparoscopic or open approach to surgery. Attempts were made to blind the subjects and the observers obtaining outcome data to treatment group. Analyses were adjusted for surgeon experience. MAIN OUTCOME MEASURES: Absence of USI 6 months following surgery, postoperative pain, time spent in hospital, and time to return to activities of normal daily living. RESULTS: There were no significant differences in objective and subjective measures of cure and in patient satisfaction at 6 months, 24 months, or 3-5 years of follow up between laparoscopic and open colposuspension groups. Laparoscopic colposuspension took longer time to perform (87 versus 42 minutes, P< 0.0001) but was associated with less blood loss (P = 0.03), less pain (P = 0.02), and quicker return to normal activities (P = 0.01). CONCLUSION: LBC has significant advantages over traditional OBC, without any apparent compromise in short-term and long-term outcomes. To compare perioperative characteristics, short-term, and long-term outcomes for laparoscopic Burch colposuspension (LBC) and open Burch colposuspension (OBC) for the treatment of urinary stress incontinence. Randomised surgical trial with single blinding. Three tertiary level teaching hospitals involving seven surgeons of varying skill levels. Two hundred women with urodynamic stress incontinence (USI). The two groups were treated in identical fashion, except for the laparoscopic or open approach to surgery. Attempts were made to blind the subjects and the observers obtaining outcome data to treatment group. Analyses were adjusted for surgeon experience. Absence of USI 6 months following surgery, postoperative pain, time spent in hospital, and time to return to activities of normal daily living. There were no significant differences in objective and subjective measures of cure and in patient satisfaction at 6 months, 24 months, or 3-5 years of follow up between laparoscopic and open colposuspension groups. Laparoscopic colposuspension took longer time to perform (87 versus 42 minutes, P < 0.0001) but was associated with less blood loss (P= 0.03), less pain (P= 0.02), and quicker return to normal activities (P= 0.01). LBC has significant advantages over traditional OBC, without any apparent compromise in short-term and long-term outcomes.

Female↗
PubMed2006

Dimensional characteristics of DSM-IV personality disorders in a large epidemiological sample.

OBJECTIVE: To assess the five-factor model (FFM) characteristics of young adults with Diagnostic Statistical Manual-IV (DSM-IV) personality disorders in a large community study. METHOD: As part of the eighth wave of a cohort study, 1469 young adults (mean age: 24 years) completed the NEO-five factor inventory, 1145 of whom also had an informant-based personality disorder assessment. RESULTS: The prevalence of personality disorder was 18.6% (95% CI: 16.5-20.7). There were consistent positive associations with neuroticism and negative associations with agreeableness across all three clusters of personality disorder. CONCLUSION: In young adults, high neuroticism and low agreeableness are consistent dimensional characteristics of all personality disorder clusters.

Adult↗
PubMed2005

The use of fingernails as a means of assessing bone health: a pilot study.

BACKGROUND: Anecdotally, patients volunteer reports of increasing hardness of their fingernails within months of starting diverse treatments for osteoporosis. The properties of both nail and bone may be linked in a comparable, measurable way. METHODS: We examined the fingernails of two groups of patients, with (n = 9) and without (n = 13) osteoporosis at either the hip or lumbosacral spine. We performed nanoindentation to assess the degree of nail brittleness and Raman spectroscopy to assess the disulfide bond content of nail. RESULTS: The mean moduli of fingernails of patients with low bone mineral density (BMD) are lower than those of patients with normal BMD. The mean difference in mean modulus between the groups was found to be 0.996 (p = 0.15 between groups). The spectroscopy data also showed differences between the two sets of nails. The disulfide bond content of the nails sourced from osteoporotic patients was lower than that from healthy patients (p = 0.06 between groups). CONCLUSIONS: Bone collagen and nail keratin are two distinct structural proteins, and both require protein sulfation and disulfide bond formation, via cysteine, for structural integrity. A disorder of either process may lead to disordered collagen and keratin synthesis. This is reflected in the structural abnormalities seen in clinical syndromes in which there is either protein deficiency, disorders of sulfur metabolism, or cystathione beta-synthase deficiency. The relationship between nail and bone may exist in a measurable way. This pilot study should lead to further work to explore this relationship. Could nail prove to be a valuable adjunct to diagnosis or provide a means of more rapid follow-up after commencement of therapy?

Aged↗
PubMed2005

Parasuicide assessment in the emergency department.

Parasuicide is an important predictor of future suicide. We collected information on all parasuicides presenting to the emergency department of a general hospital over a 3-month period. We examined detection rates, referral patterns and compared emergency department risk assessments of parasuicide with those of the psychiatric liaison team. We detected 123 parasuicides. One hundred and five (85.4%) were detected in the emergency department. Ninety-five (77.2%) were referred to the liaison psychiatry service. Liaison psychiatric risk assessment agreed with emergency department risk assessment in all cases that emergency doctors judged to be at low risk of suicide. However in cases that emergency doctors judged to be high risk the liaison assessment agreed in only 38.5% of cases. Emergency doctors appear to be appropriately cautious in their assessment of risk. However, parasuicides regularly go undetected in hospital and are not always referred for psychiatric evaluation when detected. More training in the detection, assessment and management of parasuicide is required for emergency doctors.

Adolescent↗
PubMed2004

Interleukin-8 is involved in cervical dilatation but not in prelabour cervical ripening.

Our aim was to determine the amount and source of interleukin (IL)-8 and to study IL-8 receptor expression in the human cervix during pregnancy and after labour. Cervical biopsies were obtained from six non-pregnant women, eight women undergoing pregnancy termination, 17 women undergoing elective caesarean section and 11 women after vaginal delivery. IL-8 levels were compared in women with and without a ripe cervix, as determined by cervical Bishop score and cervicovaginal fetal fibronectin levels. Levels of IL-8 and IL-1beta, a regulator of IL-8 expression, were determined by enzyme-linked immunosorbent assay (ELISA). IL-8, IL-1beta and IL-8 receptor proteins were localized by immunohistochemistry. Compared with late pregnancy, IL-8 levels increased after labour and vaginal delivery (P < 0.01) but there was no correlation with cervical ripening. IL-8 was localized to stromal cells, macrophages and granulocytes. There were no significant differences in IL-1beta levels between groups. IL-8 receptors were expressed primarily on granulocytes and macrophages after vaginal delivery. We conclude that IL-8 is involved in cervical dilatation but not in cervical ripening.

Cervical Ripening↗
PubMed2003

Does co-morbid personality disorder increase the risk of suicidal behaviour in psychosis?

OBJECTIVE: To examine the association between co-morbid personality disorder (PD) and suicidal behaviour over a 2-year period in a sample of patients with psychosis. METHOD: A total of 670 patients with established psychotic illness were interviewed using a battery of instruments including a screen for co-morbid PD. The prevalence of attempted and completed suicide was measured over the next 2 years using multiple data sources. Logistic regression was used to examine whether those with co-morbid PD were at greater risk of suicidal behaviour compared with others. RESULTS: One hundred and eighty six patients (28%) were rated as having a co-morbid PD. After adjusting for all covariates, patients with co-morbid PD were significantly more likely to attempt or complete suicide over the 2-year period (adjusted odds ratio: 1.87; 95% CI: 1.02-3.42). CONCLUSION: Co-morbid PD is independently associated with an increased risk of suicidal behaviour in psychosis. Early assessment of personality status should be part of the routine assessment of all psychiatric patients.

Adult↗
PubMed2003

Nuclear DNA identification of migrating bull trout captured at the Puget Sound Energy diversion dam on the White River, Washington State.

Bull trout (Salvelinus confluentus) is a char listed as threatened under the United States Endangered Species Act throughout its range in the coterminous United States. Substantial morphological similarities between bull trout and Dolly Varden (S. malma) make field identification difficult. This has resulted in an incomplete understanding of their distribution and abundance in Washington State where these two species occur sympatrically. We used three diagnostic nuclear loci to determine the species of char collected at a trap on the White River in southern Puget Sound (Washington State, USA). Each of the 104 samples revealed the expected bull trout genotype at all three loci. This work presents three principle results: (i) the presence of a migratory bull trout population in southern Puget Sound; (ii) no evidence of migratory Dolly Varden over 3 years; and (iii) no evidence of hybridization was detected. These results also demonstrate how molecular markers can provide information essential to the conservation and management of these species.

Animal Migration↗
PubMed2002

Interspecific barriers between salmonids when hybridisation is due to sneak mating.

Male sneaking behaviour can lead to interspecific hybridisation if sneakers attempt to fertilise ova in heterospecific mating, contributing to break down of interspecific barriers. In south European rivers, sneaking Atlantic salmon males fertilise an important proportion of ova from adult females in heterospecific crosses, up to 65%. In a south French flow-controlled stream, we found that they were able to naturally fertilise brown trout ova in absence of brown trout males. Aggressiveness of brown trout males towards sneaking salmon males and low survival of hybrids issued from salmon sneakers are found to be interspecific barriers.

Animals↗
PubMed2002

Management of hyperemesis gravidarum: the importance of weight loss as a criterion for steroid therapy.

BACKGROUND: Although the effectiveness of prednisolone therapy for severe hyperemesis gravidarum has been demonstrated, there is no consensus on how to assess severity to justify such treatment, nor any information on whether such therapy affects birth weight. AIM: To document the effect of prednisolone therapy in women with defined severity of hyperemesis gravidarum. DESIGN: Single centre, observational study of 30 consecutive pregnancies complicated by hyperemesis and weight loss of >5% of pre-pregnant weight between April 1995 and July 2000. Comparison of birth weight with a contemporaneous control series of women admitted with hyperemesis that was judged insufficiently severe to require steroids. RESULTS: Treatment with prednisolone 10 mg tid rapid resolved nausea and vomiting, allowing discharge in 3 (range 1-6.5) days. Steroid therapy, which was reduced in a stepwise manner, was discontinued at a median gestation of 20 weeks. Maternal weight gain in pregnancy was restored to normal. Median birth weight in the severe, steroid-treated group was 3.33 (range 2.80-3.27) kg vs. 3.27 (range 3.04-3.53) kg in the less severe group. CONCLUSION: Weight loss >5% served as a criterion to define a subset of women with severe hyperemesis gravidarum. In these women, steroid therapy was uniformly successful resulting in the prompt resolution of symptoms. Steroid therapy did not affect birth weight.

Adult↗
PubMed2001

The tissue factor region that interacts with factor Xa in the activation of factor VII.

Tissue factor is the cell membrane-anchored cofactor for factor VIIa and triggers the coagulation reactions. The initial step is the conversion of factor VII to factor VIIa which, in vitro, is efficiently catalyzed by low concentrations of factor Xa. To identify the tissue factor region that interacts with the activator factor Xa during this process, we evaluated a panel of soluble tissue factor (1-219) mutants for their ability to support factor Xa-mediated activation of factor VII. The tissue factor residues identified as most important for this interaction (Tyr157, Lys159, Ser163, Gly164, Lys165, Lys166, and Tyr185) were identical to those found to be important for the interaction of substrate factor X with the tissue factor.factor VIIa complex. The residues form a continuous surface-exposed patch with an area of about 500 A(2), which appears to be located outside the tissue factor-factor VII contact zone. In agreement, the two monoclonal antibodies 5G6 and D3H44-F(ab')(2), whose epitopes overlap with this identified region, inhibited the rates of factor VII activation by 86% and 95%, respectively. These antibodies also strongly inhibited the conversion of (125)I-labeled factor VII when cell membrane-expressed, full-length tissue factor (1-263) was employed. Together the results suggest the usage of a common surface region of tissue factor in its dual role-as a cofactor for factor Xa-mediated factor VII activation and as a cofactor for factor VIIa-mediated factor X activation. The finding that factor Xa and factor X may engage in similar, if not identical, molecular interactions with tissue factor further indicates that factor Xa and factor X are similarly oriented toward their respective interaction partners in the ternary catalytic complexes.

1-Carboxyglutamic Acid↗
PubMed2001

Pubovaginal or vicryl mesh rectus fascia sling in intrinsic sphincter deficiency.

The aim of this study was to compare the pubovaginal sling with a new Vicryl mesh rectus fascia (VMRF) sling in the surgical treatment of low urethral pressure genuine stress incontinence. Fifty-one consecutive women who had a VMRF (n = 27) or a pubovaginal sling (n = 24) procedure between March 1995 and December 1997 were evaluated. The patient-determined subjective success rate of the VMRF sling (85%) was significantly higher than that of the pubovaginal sling (58%) in women with low urethral pressure stress incontinence (P=0.03). The objective success rates following the VMRF and the pubovaginal sling were 52% and 50%, respectively. The prevalence of postoperative symptomatic voiding dysfunction and de novo detrusor instability was 7% after the VMRF sling and 25% following the pubovaginal sling (P = 0.08). The VMRF sling had a higher patient-determined success rate and a lower complication rate than the pubovaginal sling, and should be considered in the surgical management of women with low urethral pressure stress incontinence.

Adult↗
PubMed2001

The impact of personality disorder in UK primary care: a 1-year follow-up of attenders.

BACKGROUND: The usefulness of the concept of personality disorder has not been properly tested outside psychiatric services. We set out to examine this in primary care, by examining the ability of the diagnosis to predict health status and patterns of service use. METHOD: A cohort of consecutive attenders, who had previously been rated for the presence of personality disorder using a standardized assessment, was followed-up at 1 year. The participating general practitioners also rated the personalities of, and their attitudes towards, a proportion of this sample of attenders. RESULTS: After adjusting for the effects of all covariates, a rating of personality disorder (generated by the standardized assessment) was associated with frequent attendance to general practice and fewer referrals to secondary care. A GP rating of personality disorder was associated with the prescription of psychotropic medication. The level of agreement between a GP rating of personality disorder and the standardized assessment was poor. GPs rated personality disorder more frequently in participants who were perceived to be less compliant, less likeable and more stressful to deal with. Participants with a psychiatric rating of personality disorder did not attract these negative perceptions. CONCLUSIONS: Personality disorder, as rated by a research interview, is a predictor of health service usage. There is a significant disparity between a research rating of personality disorder and the diagnostic ratings made by GPs. The GP ratings of personality disorder were strongly associated with adverse perceptions of the patient's consulting behaviour.

Adult↗
PubMed2001

Profile of first-line nurse managers in New South Wales, Australia, in the 1990s.

AIMS: To determine a demographic profile, employment history and career plans of a sample of nursing unit managers (first-line managers) in New South Wales (NSW), Australia in 1999. To compare the profile of first-line nurse managers in 1999 with those in 1989. BACKGROUND: This study replicates another undertaken a decade earlier (see Duffield 1992). Tracking the changes to nurse manager positions is important, given changes to the educational preparation of nurses and restructuring within hospitals which have occurred in the past decade. METHOD: The same questionnaire was used in both studies, with minor amendments and the addition of two items to reflect changes to organizational structures, whereby nurse managers are now responsible for non-nursing staff. In 1999 all first-line nurse managers in the largest health service in NSW were invited to participate in the study. RESULTS: A response rate of 77% was achieved. There were few differences of note in the demographic profile from 1989 to 1999. However educationally, first-line nurse managers in 1999 were more highly qualified. A greater proportion had higher degrees and increasingly, in the management discipline. CONCLUSION: Perhaps reflecting these qualifications, more managers in 1999 indicated their intention to move to more senior management positions in the next decade. The mode for experience in this role of 1 year in both 1989 and 1999 reflects a worrying trend of high turnover and inexperience amongst this group of managers. While maternity relief might account for this result, further research needs to determine more precise reasons. The ad hoc bases on which expert clinicians (clinical nurse specialists) act as the manager in his/her absence need to be critically examined. Alternative strategies such as introducing a formal second- in-charge position may ensure more successful recruitment and retention of staff to these critical management positions.

Adult↗
PubMed2001

Generation of a humanized, high affinity anti-tissue factor antibody for use as a novel antithrombotic therapeutic.

Blocking the cofactor function of human tissue factor may be beneficial in various coagulation-mediated diseases. The murine antibody D3 binds to the membrane proximal substrate interaction region of human tissue factor and blocks tissue factor function even in the presence of bound factor VIIa. The cloned murine D3 antibody was humanized and affinity matured by exchanging amino acids in the complementarity determining regions as well as in the antibody framework. The humanized antibody, D3H44, bound to tissue factor with a 100-fold increased affinity (KD 0.1 nM) as compared to the original murine and chimeric versions. Depending on the particular disease, different pharmacokinetic properties of the antibody may be required and, therefore, several antibody variants-- F(ab), F(ab')2, IgG2, IgG4 and IgG4b-were generated. In vitro, the humanized D3 antibodies displayed potent inhibition of plasma clotting and tissue factor: factor VIIa-mediated activation of factors IX and X (e.g. D3H44-F(ab')2, IC50(F.X) 47 pM). In addition, D3H44-F(ab')2 completely prevented fibrin deposition in a human ex vivo thrombosis model under venous blood flow conditions (IC50 37 nM). The humanized D3 antibodies may be utilized for treatment of cardiovascular diseases which involve tissue factor activity, e.g. acute coronary syndrome and venous thrombosis.

Amino Acid Sequence↗
PubMed2000

The tissue factor region that interacts with substrates factor IX and Factor X.

The enzymatic activity of coagulation factor VIIa is controlled by its cellular cofactor tissue factor (TF). TF binds factor VIIa with high affinity and, in addition, participates in substrate interaction through its C-terminal fibronectin type III domain. We analyzed surface-exposed residues in the C-terminal TF domain to more fully determine the area on TF important for substrate activation. Soluble TF (sTF) mutants were expressed in E. coli, and their ability to support factor VIIa-dependent substrate activation was measured in the presence of phospholipid vesicles or SW-13 cell membranes. The results showed that factor IX and factor X interacted with the same TF region located proximal to the putative phospholipid surface. According to the degree of activity loss of the sTF mutants, this TF region can be divided into a main region (residues Tyr157, Lys159, Ser163, Gly164, Lys165, Lys166, Tyr185) forming a solvent-exposed patch of 488 A(2) and an extended region which comprises an additional 7-8 residues, including the distally positioned Asn199, Arg200, and Asp204. Some of the identified TF residues, such as Trp158 and those within the loop Lys159-Lys165, are near the factor VIIa gamma-carboxyglutamic acid (Gla) domain, suggesting that the factor VIIa Gla-domain may also participate in substrate interaction. Moreover, the surface identified as important for substrate interaction carries a net positive charge, suggesting that charge interactions may significantly contribute to TF-substrate binding. The calculated surface-exposed area of this substrate interaction region is about 1100 A(2), which is approximately half the size of the TF area that is in contact with factor VIIa. Therefore, a substantial portion of the TF surface (3000 A(2)) is engaged in protein-protein interactions during substrate catalysis.

Amides↗
PubMed2000

The prevalence of personality disorder among UK primary care attenders.

OBJECTIVE: To determine the prevalence rate of personality disorder among a consecutive sample of UK primary care attenders. Associations between a diagnosis of personality disorder, sociodemographic background and common mental disorder were examined. METHOD: Three hundred and three consecutive primary care attenders were examined for the presence of ICD-10 and DSM-4 personality disorders using an informant-based interview. RESULTS: Personality disorder was diagnosed in 24% (95% CI: 19-29) of the sample. Personality-disordered subjects were more likely to have psychiatric morbidity as indicated by GHQ-12, to report previous psychological morbidity, to be single and to attend the surgery on an emergency basis. 'Cluster B' personality disorders were particularly associated with psychiatric morbidity. CONCLUSION: There is a high prevalence rate of personality disorders among primary care attenders. These disorders are associated with the presence of common mental disorder and unplanned surgery attendance. Personality disorders may represent a significant source of burden in primary care.

Adult↗