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Biomedical subjects

C Shaw

Publications and source records attributed to C Shaw.

At least 19 recordsLinked to original sources
PubMed2003

An investigation into nonresponse bias in a postal survey on urinary symptoms.

OBJECTIVE: To investigate nonresponse bias in a postal survey on urinary symptoms in people aged >or= 40 years. SUBJECTS AND METHODS: Nonresponders to a postal survey on incontinence and other urinary symptoms were studied. A random sample of 1050 nonresponders (stratified for age and sex) was traced by a team of interviewers. Eligible nonresponders were asked several questions from the postal questionnaire, and their reason for not participating in the postal survey. RESULTS: Only 1% of those not responding were not traced in person or accounted for, and 12% were identified as not eligible to be in the survey sample (moved from address, deceased, residential home). Half of the eligible nonresponders (51%) did not answer the interviewer's questions, the main reason being general unwillingness or disinterest. The number in whom poor health was the reason increased with age. Comparing nonresponders who answered the interviewer's questions with a random sample of responders from the postal survey showed little difference in the reporting of urinary symptoms, although there were differences in general health and long-term health problems. Separate analyses by age showed greater reporting of some urinary symptoms and of poorer general health in the older nonresponders (>or= 70 years). CONCLUSION: Overall, for people aged >or= 40 years there was no evidence of a nonresponse bias in the reporting of urinary symptoms, providing confidence in such prevalence rates. However, poorer general health and greater reporting of some urinary symptoms by the older nonresponders (>or= 70 years) suggests prevalence rates in this age group may be underestimated.

Adult↗
PubMed2002

Variability of Nt-proANP and C-ANP.

BACKGROUND: Natriuretic peptides are frequently measured in patients with chronic cardiac failure (CCF). We set out to compare the variability of atrial natriuretic peptide (C-ANP) and its precursor N-terminal pro-ANP (Nt-proANP) to decide which would be more suitable for routine use. METHODS: Ten males with compensated CCF (age range 62-76 years) were studied, with matched controls. Blood was withdrawn every 2 min for 90 min from a forearm vein, and plasma C-ANP and Nt-proANP were measured by radioimmunoassay. RESULTS: Levels were elevated in the patient group [C-ANP: median 268 (range 171-423) vs. 40 (28-56) ng L-1, P < 0.0002 Mann-Whitney U-test; Nt-proANP: 1955 (562-4451) vs. 621 (409-961) pmol L-1, P < 0.003]. A similar number of 'peaks' was observed in both groups with both peptides, about one every 10 min, and their relative height was similar in both groups. Variability was greater for C-ANP than for Nt-proANP in both patients [coefficient of variation of means 51 (range 36-70) vs. 3.6 (2.1-6.2)%, P < 0.01; sign test] and controls [65 (49-83) vs. 8.9 (4.7-13.5)%, P < 0.01]. CONCLUSION: Nt-proANP is less variable than C-ANP and hence more suited for diagnostic or prognostic use.

Aged↗
PubMed2002

Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in pulp tissue from painful and healthy human teeth.

AIM: The purpose of this study was to investigate the levels of substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) in painful and healthy human dental pulps. METHODOLOGY: Forty-six samples of pulp tissue were collected from extracted or endodontically treated painful teeth and 20 from clinically healthy teeth extracted for orthodontic reasons. All pulp samples were boiled in 0.5 m acetic acid for 10 min, centrifuged and the supernatant collected. SP, NKA and CGRP levels were measured using radioimmunoassay. RESULTS: Substance P and CGRP were present in all samples and NKA was detected in 96% of the pulps. CGRP was present in much higher concentrations than SP and NKA in both painful and non-painful teeth. The painful teeth had significantly higher concentrations of SP (P = 0.02), NKA (P < 0.001) and CGRP (P = 0.03) than non-painful teeth. The concentration of CGRP was significantly higher in the pulps of smokers compared with non-smokers (P = 0.02). CONCLUSIONS: Elevated levels of these neuropeptides in pulps from painful teeth indicate that they may play an important role in the process of pulpal inflammation and pain. Further investigation of the association between these neuropeptides and pulpal status may help to improve our understanding of pulpal inflammation and dental pain.

Adolescent↗
PubMed2002

Validity and reliability of an interviewer-administered questionnaire to measure the severity of lower urinary tract symptoms of storage abnormality: the Leicester Urinary Symptom Questionnaire.

OBJECTIVE: To develop a valid and reliable interviewer-administered questionnaire to measure the presence and severity of storage abnormality symptoms of incontinence, urgency, frequency and nocturia. SUBJECTS AND METHODS: Subjects were 930 men and women aged >/=40 years, taking part in a randomized controlled trial of a continence nurse practitioner (CNP) service. Criterion validity was tested by comparing questionnaire responses to 24-h pad test and 3-day urinary diary. Responsiveness was assessed by comparing questionnaire responses before and after treatment. Questions about urgency were investigated for construct validity in patients taking part in the trial who underwent urodynamic investigation (243). Test-retest and inter-rater reliability was measured at approximately 6 days in subjects recruited to an associated epidemiological study (104 and 102, respectively). RESULTS: The questionnaire responses showed significant associations with pad-test and diary measures. Questions about the severity of daytime incontinence performed better than those measuring night-time incontinence. The response categories of soaked, wet, damp and almost dry had better associations with the pad test than other measures of the severity of incontinence. Test-retest and inter-rater reliability was good for all questions, and all were responsive to change in symptoms, showing significant differences before and after treatment. CONCLUSION: There is a clear need for standardization of measurement using well-validated instruments. This interviewer-administered questionnaire is valid, reliable and sensitive to change in a wide range of severity of symptoms, and in both men and women aged >/=40 years. The questionnaire provides a useful assessment tool for primary and secondary care in research and clinical settings.

Aged↗
PubMed2002

Prevalence of faecal incontinence in adults aged 40 years or more living in the community.

BACKGROUND: Prevalence studies of faecal incontinence in the general population are rare and the impact of faecal incontinence on quality of life has not been previously addressed. AIMS: To establish the prevalence of faecal incontinence in adults in terms of frequency of leakage, degree of soiling, and level of impact on quality of life. METHODS: In a cross sectional postal survey, 15 904 adults aged 40 years or more (excluding residents of nursing and residential homes) were selected randomly by household from the Leicestershire Health Authority patient register. Participants were asked to complete a confidential health questionnaire. Major faecal incontinence was defined as soiling of underwear or worse with a frequency of several times a month or more. Respondents were also asked if bowel symptoms had an impact on their quality of life. RESULTS: From a total sample of 10 116 respondents, 1.4% reported major faecal incontinence and 0.7% major faecal incontinence with bowel symptoms that had an impact on quality of life. Major faecal incontinence was significantly associated with a lot of impact on quality of life (odds ratio 12.4, 95% confidence interval 7.5-20.6). Incontinence was more prevalent and more severe in older people but there was no significant difference between men and women. CONCLUSIONS: This study has confirmed that faecal incontinence is a fairly common symptom, particularly in older people. Faecal incontinence in men has received little attention in the past and the results from this study indicate that it is as much of a problem in men as it is in women while the level of unmet need in this group is high. Estimates of need for health care for this symptom should be multidimensional and assess both the severity of symptoms and the impact it has on quality of life.

Adult↗
PubMed2001

A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations.

Incontinentia pigmenti (IP) is an X-linked dominant disorder characterized by abnormal skin pigmentation, retinal detachment, anodontia, alopecia, nail dystrophy and central nervous system defects. This disorder segregates as a male lethal disorder and causes skewed X-inactivation in female patients. IP is caused by mutations in a gene called NEMO, which encodes a regulatory component of the IkappaB kinase complex required to activate the NF-kappaB pathway. Here we report the identification of 277 mutations in 357 unrelated IP patients. An identical genomic deletion within NEMO accounted for 90% of the identified mutations. The remaining mutations were small duplications, substitutions and deletions. Nearly all NEMO mutations caused frameshift and premature protein truncation, which are predicted to eliminate NEMO function and cause cell lethality. Examination of families transmitting the recurrent deletion revealed that the rearrangement occurred in the paternal germline in most cases, indicating that it arises predominantly by intrachromosomal misalignment during meiosis. Expression analysis of human and mouse NEMO/Nemo showed that the gene becomes active early during embryogenesis and is expressed ubiquitously. These data confirm the involvement of NEMO in IP and will help elucidate the mechanism underlying the manifestation of this disorder and the in vivo function of NEMO. Based on these and other recent findings, we propose a model to explain the pathogenesis of this complex disorder.

Blotting, Northern↗
PubMed2001

Isolation and preliminary biological assessment of AADGAPLIRFamide and SVPGVLRFamide from Caenorhabditis elegans.

To date, 9 FMRFamide-related peptides (FaRPs) have been structurally characterised from Caenorhabditis elegans. Radioimmunometrical screening of an ethanolic extract of C. elegans revealed the presence of two additional FaRPs that were purified by reverse-phase HPLC and subjected to Edman degradation analysis and gas-phase sequencing. Unequivocal primary structures for the two FaRPs were determined as Ala-Ala-Asp-Gly-Ala-Pro-Leu-Ile-Arg-Phe-NH(2) and Ser-Val-Pro-Gly-Val-Leu-Arg-Phe-NH(2). Using MALDI-TOF mass spectrometry, the molecular masses of the peptides were found to be 1032 Da (MH) and 875 Da (MH)(+), respectively. Two copies of AADGAPLIRFamide are predicted to be encoded on the precursor gene termed flp-13, while one copy of SVPGVLRFamide is located on flp-18. Synthetic replicates of the peptides were tested on Ascaris suum somatic muscle to assess bioactivity. ADDGAPLIRFamide had inhibitory effects on A. suum muscle strips, which occurred over a range of concentrations from a threshold for activity of 10 nM to 10 microM. SVPGVLRFamide was excitatory on A. suum somatic musculature from a threshold concentration for activity of 1 nM to 10 microM. The inhibitory and excitatory effects of AADGAPLIRFamide and SVPGVLRFamide, respectively, were the same for dorsal and ventral muscle strips as well as innervated and denervated preparations, suggesting that these physiological effects are not nerve cord dependent. Addition of ADDGAPLIRFamide (10 microM) to muscle strips preincubated in high-K(+) and -Ca(2+)-free medium resulted in a normal inhibitory response. Peptide addition to muscle strips preincubated in Cl(-)-free medium showed no inhibitory response, suggesting that the inhibitory response of the peptide may be chloride mediated. A normal excitatory response was noted following the addition of 10 microM SVPGVLRFamide to muscle strips preincubated in high-K(+), Ca(2+)- and Cl(-)-free media.

Animals↗
PubMed2001

Quantitative analysis of MRP-8 in gingival crevicular fluid in periodontal health and disease using microbore HPLC.

BACKGROUND: The protein components of GCF can be separated by reverse-phase microbore HPLC on a C18 column with detection on the basis of 214 nm absorbance. A single major symmetrical protein peak eluting with a retention time of 26 min (50% acetonitrile) was evident in gingival crevicular fluid (GCF) from periodontitis patients but not in healthy GCF. This protein was identified as human MRP-8 by N-terminal amino acid sequencing and liquid chromatography quadropole mass spectrometry. AIMS: To quantify the amount of MRP-8 detectable in GCF from individual healthy, gingivitis and periodontitis affected sites and to study the relationship, if any, between the levels of this responsive protein and periodontal health and disease. METHODS: GCF was sampled (30 s) from healthy, gingivitis, and periodontitis sites in peridontitis subjects (n=15) and from controls (n=5) with clinically healthy gingiva and no periodontitis. Purified MRP-8 was sequenced by Edmann degradation and the phenylthiohydantoin (PTH) amino acid yield determined (by comparison of peak area with external PTH amino acid standards). This value was subsequently used to calculate the relative amount of protein in the peak eluting with a retention time of 26.0 min (MRP-8) in individual GCF chromatograms. RESULTS: Higher levels of MRP-8 were detected in inflammatory sites: periodontitis 457.0 (281.0) ng; gingivitis 413.5 (394.5) ng compared with periodontally healthy sites in diseased subjects 14.6 (14.3) ng and in controls 18.6 (18.5) ng, p=0.003. There was at least 20-fold more MRP-8 in the inflammatory compared with the healthy sites studied. CONCLUSIONS: The preliminary data indicate that MRP-8 is present in GCF, with significantly greater amounts present at diseased than healthy sites. A systematic study of the relationship of this protein to periodontal disease could prove useful in further clarifying whether MRP-8 could be a reliable GCF biomarker of gingivitis and periodontitis.

Adult↗
PubMed2001

A review of the psychosocial predictors of help-seeking behaviour and impact on quality of life in people with urinary incontinence.

Although urinary incontinence is common and can have a substantial impact on an individual's quality of life, few people seek help for this symptom. This paper examines a theoretical framework proposed by Shaw (1999) as a possible explanatory model for help-seeking and the impact of incontinence on a person's quality of life. Although aetiology and symptom severity are important predictors of behaviour and impact of symptoms, they did not explain all the variation and so other predictors proposed by the model were explored. Appraisals of illness and coping resources were found to be important moderating factors between the experience of symptoms and subsequent behaviour and outcome in urinary incontinence. In the appraisal of symptoms, lack of knowledge of the causes and treatments of urinary incontinence can be a barrier to help-seeking and successful outcome. Other factors such as personality, group differences, and social support can contribute to the appraisal process. Areas for future research and implications for clinical practice are discussed.

Adaptation, Psychological↗
PubMed2001

Barriers to help seeking in people with urinary symptoms.

BACKGROUND: Urinary incontinence is a common problem but, for those experiencing significant clinical symptoms, help seeking has been reported to be as low as 20%. As many of these people could be helped by simple interventions, there is a clear need to identify barriers to help seeking and develop interventions to overcome these barriers. OBJECTIVES: This study explores help-seeking behaviour in people with urinary symptoms such as leakage, frequency, nocturia and urgency in order to identify barriers to service use. METHOD: Thirty-one people who either had agreed to treatment as part of an intervention study or who were receiving treatment at a hospital out-patient clinic for their urinary problems took part in unstructured, taped interviews. Respondents were questioned about their views on help seeking for urinary problems and their personal experiences of consultations. The data were transcribed, coded and thematic analysis carried out. RESULTS: The most common theme to emerge was a lack of knowledge of the condition and of available treatments. Urinary symptoms frequently were considered a normal part of ageing or childbirth, or it was felt that these types of symptoms were inappropriate for medical intervention. Older people were not only more likely to accept symptoms but were also less likely to want to bother their GP. Patients did not always communicate their concerns about urinary symptoms to their GP, through either embarrassment or misconceptions of what is a 'medical problem'. CONCLUSIONS: There is a clear need for health education and health promotion in this area. Future work should explore professionals' knowledge and views of these types of conditions with the aim of providing guidelines for management in primary care.

Adult↗
PubMed2001

Trafficking of GFP-tagged DeltaF508-CFTR to the plasma membrane in a polarized epithelial cell line.

The DeltaF508 mutation reduces the amount of cystic fibrosis transmembrane conductance regulator (CFTR) expressed in the plasma membrane of epithelial cells. However, a reduced temperature, butyrate compounds, and "chemical chaperones" allow DeltaF508-CFTR to traffic to the plasma membrane and increase Cl(-) permeability in heterologous and nonpolarized cells. Because trafficking is affected by the polarized state of epithelial cells and is cell-type dependent, our goal was to determine whether these maneuvers induce DeltaF508-CFTR trafficking to the apical plasma membrane in polarized epithelial cells. To this end, we generated and characterized a line of polarized Madin-Darby canine kidney (MDCK) cells stably expressing DeltaF508-CFTR tagged with green fluorescent protein (GFP). A reduced temperature, glycerol, butyrate, or DMSO had no effect on 8-(4-chlorophenylthio)-cAMP (CPT-cAMP)-stimulated transepithelial Cl(-) secretion across polarized monolayers. However, when the basolateral membrane was permeabilized, butyrate, but not the other experimental maneuvers, increased the CPT-cAMP-stimulated Cl(-) current across the apical plasma membrane. Thus butyrate increased the amount of functional DeltaF508-CFTR in the apical plasma membrane. Butyrate failed to stimulate transepithelial Cl(-) secretion because of inhibitory effects on Cl(-) uptake across the basolateral membrane. These observations suggest that studies on heterologous and nonpolarized cells should be interpreted cautiously. The GFP tag on DeltaF508-CFTR will allow investigation of DeltaF508-CFTR trafficking in living, polarized MDCK epithelial cells in real time.

Animals↗
PubMed2001

United Kingdom population trends in the 21st century.

This article considers the likely trends in population size, age structure and potential support ratios in the United Kingdom over the coming century. The extent to which these trends could be modified by changes in fertility or migration levels is examined. The findings of a recent United Nations report on 'Replacement Migration' are also considered in the light of the Government Actuary's official population projections for the United Kingdom' together with new projection scenarios prepared specially for this article.

Adolescent↗
PubMed2001

Optimal methods for guideline implementation: conclusions from Leeds Castle meeting.

BACKGROUND: Quality problems in medical care are not a new finding. Variations in medical practice as well as actual medical errors have been pointed out for many decades. The current movement to write practice guidelines to attempt to correct these deviations from recommended medical practice has not solved the problem. OBJECTIVE: In order to gain greater acceptance of these guidelines and to change the behavior of health care providers, the science of guideline implementation must be understood better. RESEARCH DESIGN: A group of experts who have studied the problem of implementation in Europe and the United States was convened. This meeting summary enumerates the implementation methods studied to date, reviews the theories of behavioral change, and makes recommendation for effecting better implementation guidelines. RESULTS: A research agenda was proposed to further our knowledge of effective evidence-based implementation.

Europe↗
PubMed2001

Assumptions for the 2000-based national population projections.

This article summarises the long-term assumptions of fertility, mortality and net migration which will underlie the forthcoming 2000-based national population projections. Compared with the current (1998-based) projections, the new projections will assume lower levels of fertility, but higher levels of inward net migration. There will be relatively little change to mortality assumptions. Results of the new projections will be available on 15 November 2001.

Birth Rate↗
PubMed2000

Peptide leucine arginine, a potent immunomodulatory peptide isolated and structurally characterized from the skin of the Northern Leopard frog, Rana pipiens.

On the basis of histamine release from rat peritoneal mast cells, an octadecapeptide was isolated from the skin extract of the Northern Leopard frog (Rana pipiens). This peptide was purified to homogeneity using reversed-phase high performance liquid chromatography and found to have the following primary structure by Edman degradation and pyridylethylation: LVRGCWTKSYPPKPCFVR, in which Cys(5) and Cys(15) are disulfide bridged. The peptide was named peptide leucine-arginine (pLR), reflecting the N- and C-terminal residues. Molecular modeling predicted that pLR possessed a rigid tertiary loop structure with flexible end regions. pLR was synthesized and elicited rapid, noncytolytic histamine release that had a 2-fold greater potency when compared with one of the most active histamine-liberating peptides, namely melittin. pLR was able to permeabilize negatively charged unilamellar lipid vesicles but not neutral vesicles, a finding that was consistent with its nonhemolytic action. pLR inhibited the early development of granulocyte macrophage colonies from bone marrow stem cells but did not induce apoptosis of the end stage granulocytes, i.e. mature neutrophils. pLR therefore displays biological activity with both granulopoietic progenitor cells and mast cells and thus represents a novel bioactive peptide from frog skin.

Adjuvants, Immunologic↗
PubMed2000

The PDZ-interacting domain of cystic fibrosis transmembrane conductance regulator is required for functional expression in the apical plasma membrane.

Polarization of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel to the apical plasma membrane in epithelial cells is critical for vectorial chloride transport. Previously, we reported that the C terminus of CFTR constitutes a PDZ-interacting domain that is required for CFTR polarization to the apical plasma membrane and interaction with the PDZ domain-containing protein EBP50 (NHERF). PDZ-interacting domains are typically composed of the C-terminal three to five amino acids, which in CFTR are QDTRL. Our goal was to identify the key amino acid(s) in the PDZ-interacting domain of CFTR with regard to its apical polarization, interaction with EBP50, and ability to mediate transepithelial chloride secretion. Point substitution of the C-terminal leucine (Leu at position 0) with alanine abrogated apical polarization of CFTR, interaction between CFTR and EBP50, efficient expression of CFTR in the apical membrane, and chloride secretion. Point substitution of the threonine (Thr at position -2) with alanine or valine had no effect on the apical polarization of CFTR, but reduced interaction between CFTR and EBP50, efficient expression of CFTR in the apical membrane as well as chloride secretion. By contrast, individual point substitution of the other C-terminal amino acids (Gln at position -4, Asp at position -3 and Arg at position -1) with alanine had no effect on measured parameters. We conclude that the PDZ-interacting domain, in particular the leucine (position 0) and threonine (position -2) residues, are required for the efficient, polarized expression of CFTR in the apical plasma membrane, interaction of CFTR with EBP50, and for the ability of CFTR to mediate chloride secretion. Mutations that delete the C terminus of CFTR may cause cystic fibrosis because CFTR is not polarized, complexed with EBP50, or efficiently expressed in the apical membrane of epithelial cells.

Animals↗
PubMed2000

Isolation, structural characterization, and bioactivity of a novel neuromedin U analog from the defensive skin secretion of the Australasian tree frog, Litoria caerulea.

We report the isolation of a novel bioactive peptide, neuromedin U-23 (NmU-23), from the defensive skin secretion of the Australasian tree frog, Litoria caerulea. The primary structure of the peptide was established by a combination of microsequencing, mass spectroscopy and site-directed antiserum immunoreactivity as SDEEVQVPGGVISNGYFLFRPRN-amide (M(r) 2580.6). A synthetic replicate of frog NmU-23 displaced monoradioiodinated rat NmU-23 from uterine membranes in a dose-dependent fashion indistinguishable from nonisotopically labeled rat NmU-23. In a rat uterine smooth muscle strip preparation, synthetic frog NmU-23 produced dose-dependent contractions identical to porcine NmU-25. However, in a preparation of human urinary bladder muscle strip, the synthetic frog peptide was more potent than porcine NmU-25 in eliciting contraction and produced desensitization of the preparation to the latter peptide. This report demonstrates that the defensive skin secretion of a frog contains a novel peptide exhibiting a high degree of primary structural similarity to the endogenous vertebrate peptide, NmU, and that this frog skin analog displays biological activity in mammalian tissues.

Amino Acid Sequence↗