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Biomedical subjects

P Lewis

Publications and source records attributed to P Lewis.

At least 19 recordsLinked to original sources
PubMed2006

Deprivation and trends in blood pressure, cholesterol, body mass index and smoking among participants of a UK primary care-based cardiovascular risk factor screening programme: both narrowing and widening in cardiovascular risk factor inequalities.

OBJECTIVES: To examine recent time trends in blood pressure (BP), total cholesterol, body mass index (BMI) and current smoking among people in the UK of different deprivation groups. DESIGN: Repeatable survey. SETTING: Primary care-based UK cardiovascular risk factor screening programme (58 Stockport general practices). PARTICIPANTS: 37,161 women and 33,977 men aged 35-60 years responding to a screening invitation and with a first screening episode during 1989-99. RESULTS: There were significant decreasing trends in total cholesterol (-0.06 mmol/l/year, 95% confidence interval (CI) -0.07 to -0.06 for women, -0.07 mmol/l/year, 95% CI -0.07 to -0.06 for men), with a significantly faster drop in more deprived groups (-0.005 mmol/year/increasing deprivation group, 95% CI -0.01 to -0.001 for both sexes). There were decreasing trends in current smoking prevalence (odds ratio (OR) 0.97/year, 95% CI 0.96 to 0.97 for women, OR 0.96/year, 95% CI 0.95 to 0.96 for men) with a significantly slower drop in the more deprived groups (OR 1.01/year/increasing deprivation group, 95% CI 1.00 to 1.01 for both sexes). There were significant increasing trends in BMI (0.11 kg/m(2)/year in women, 95% CI 0.09 to 0.13, 0.10 kg/m(2)/year in men, 95% CI 0.08 to 0.11), with a significantly slower increase in the more deprived groups among men only (-0.02 kg/m(2)/year/increasing deprivation group, 95% CI -0.01 to -0.03). Inequality in BP narrowed among men but widened among women. CONCLUSION: Inequalities in risk factors between different deprivation groups may be both widening (smoking, BP in women) and narrowing (total cholesterol, BMI and BP in men). Given baseline inequalities in risk factors levels, these trends suggest that inequalities in cardiovascular disease are likely to persist in the future.

Adult↗
PubMed2006

Use of ICM+ software for on-line analysis of intracranial and arterial pressures in head-injured patients.

OBJECTIVE: To summarize our experience from the first 2 years of use of the ICM+ software in our Neurocritical Care Unit (NCCU). MATERIALS AND METHODS: Ninety-five head-injured patients (74 males, 21 females), average age 36 years, were managed in the NCCU. Intracranial pressure (ICP) was monitored using Codman intraparenchymal probes and arterial blood pressure (ABP) was measured from the radial artery. Signals were monitored by ICM+ software calculating mean values of ICP, ABP, cerebral perfusion pressure (CPP) and various indices describing pressure reactivity, compensation and vascular waveforms of ICP (pulse amplitude, respiratory, and slow waves), etc. RESULTS: Mean ICP was 17 mmHg, mean CPP was 73 mmHg. Seven patients showed permanent disturbance of cerebral autoregulation (mean pressure reactivity index above 0.3). Pressure reactivity index demonstrated significant U-shape relationship with CPP, suggesting loss of pressure reactivity at too low (CPP < 55 mmHg) and too high CPPs (CPP > 95 mmHg). Mean ICP was inversely correlated with respiratory rate (R = 0.46; p < 0.0001; reciprocal model). CONCLUSION: The new version of ICM+ software proved to be useful clinically in the NCCU. It allows continuous monitoring of pressure reactivity and exploratory analysis of factors implicating intracranial hypertension.

Adult↗
PubMed2006

Cognitive, language and social-cognitive skills of individuals with fragile X syndrome with and without autism.

BACKGROUND: It is not known whether those with co-morbid fragile X syndrome (FXS) and autism represent a distinct subtype of FXS; whether the especially severe cognitive delays seen in studies of young children with co-morbid FXS and autism compared with those with only FXS continue into adolescence and young adulthood; and whether autism in those with FXS is 'true autism', i.e. reflects the same underlying problems as idiopathic autism. METHOD: We compared the non-verbal IQ of adolescents and young adults with co-morbid FXS and autism (n = 10) with those with only FXS (n = 44). We then created a subsample of those with FXS only, matched on non-verbal IQ, mental age and gender (n = 21) to the subsample of those with co-morbid FXS and autism. We compared the two groups on measures of expressive language, receptive language (lexical, grammatical morphology and syntactic patterns), and a theory of mind task. RESULTS: Those with co-morbid FXS and autism had lower non-verbal IQs than those with only FXS. The participants with co-morbid FXS and autism did not perform as well as the cognitive ability- and gender-matched participants with only FXS on the three measures of receptive language or the theory of mind task; there were no differences on the expressive language measure. CONCLUSIONS: Our findings support the notion that those with co-morbid FXS and autism represent a distinct subtype of FXS, with more impairment in receptive language and theory of mind even when controlling for their lower non-verbal IQ relative to those with only FXS. The greater cognitive impairments observed in those with co-morbid FXS and autism continues into adolescence and young adulthood; and the autism seen in those with FXS appears to be the same as idiopathic autism.

Adolescent↗
PubMed2006

Psychological well-being of mothers of youth with fragile X syndrome: syndrome specificity and within-syndrome variability.

BACKGROUND: Research on parental well-being has focused largely on Down syndrome and autism; however, fragile X syndrome is likely to pose different challenges for parents compared with these other diagnostic conditions. Moreover, there is considerable variability among youth with fragile X syndrome; for example, 25% to 33% of affected youth meet criteria for a co-morbid diagnosis of autism. It is likely that parents of youth with fragile X syndrome will experience different degrees and patterns of stress, depending on whether their offspring do or do not have a co-morbid diagnosis of autism. In the present study, we compared mothers of three groups of young males on measures of psychological well-being and stress: those with fragile X syndrome and a co-morbid diagnosis of autism; those with fragile X syndrome alone; and those with Down syndrome. METHOD: The sample consisted of mothers of adolescent and young adult males with fragile X syndrome and co-morbid autism (n=9), fragile X syndrome alone (n=19), and Down syndrome (n=19). We screened all youth for autism using the Autism Behavior Checklist, which was completed by mothers, fathers and teachers, and the youth who scored above the suggested cut-off were evaluated by a licensed psychologist to determine autism status. The three groups of youth did not differ in chronological age (16.4, 15.8 and 16.0 years, respectively) or non-verbal mental age (3.8, 3.9 and 3.8 years, respectively). Several self-report measures were completed by mothers. These measures assessed current mental health status (e.g. the Center for Epidemiological Studies Depression Scale), perceptions of their son's and family's functioning (e.g. the Positive Affect Index, which measures closeness felt by the mother to her son and also reciprocated closeness felt by the son towards the mother, as perceived by the mother), and approach to coping with their son's disability [e.g. the Multidimensional Coping Inventory (COPE), which measures emotion-focused and problem-solving focused coping]. RESULTS: The results suggest that fragile X syndrome creates more challenges to maternal psychological well-being than Down syndrome, and that the combination of fragile X syndrome and autism can be particularly challenging. Differences among groups, however, were manifested mainly as concerns about the affected son and about relationships within the family rather than as lower levels of mental health. Thus, mothers of sons with fragile X syndrome, regardless of the son's autism status, reported more pessimism about the son's future and more conflict within the family than mothers of sons with Down syndrome. Additionally, mothers of sons with fragile X syndrome and co-morbid autism reported lower levels of reciprocated closeness than the other two groups of mothers. CONCLUSION: We consider possible causes of these maternal differences, the implications for clinical practice, needs for future research, and the importance of understanding child and contextual factors as well as the dynamics leading to these differences.

Adaptation, Psychological↗
PubMed2005

Survival among hospital in-patients with troponin T elevation below levels defining myocardial infarction.

BACKGROUND: Cardiac troponin T (cTnT) has an accepted place in the management of patients presenting with suspected acute coronary syndrome (ACS). Uncertainty remains about the significance and interpretation of elevated cTnT below the cut-off levels defining myocardial infarction (0.1 microg/l). AIM: To compare the mortality risks for elevation of cTnT in the ranges 0.01-0.029 microg/l, 0.03-0.099 microg/l and <0.01 microg/l. DESIGN: Retrospective record study in three hospitals. METHODS: All cTnT measurements with values in the range >0.01-0.099 microg/l analysed during January 2002 were extracted from clinical biochemistry laboratory databases. Following agreed exclusion criteria, 179 patients with cTnT in the range 0.01-0.099 microg/l and 60 patients <0.01 microg/l were selected at random from across the three sites. Six-month follow-up was completed by review of case notes and contact with the patients' GP. RESULTS: There was a graded increase in mortality with increasing cTnT, although only achieving statistical significance for patients in the 0.03-0.099 microg/l range. The graded increase in relative risk with cTnT was weaker after adjustment for potential confounding factors DISCUSSION: We found a trend for worse survival with increasing cTnT within the range 0.01-0.099 microg/l in unselected patient populations presenting with possible acute coronary syndrome. This suggests that the combined effects of assay imprecision and co-morbidity should be taken into account when interpreting borderline elevation of cTnT. The use of a cut-off based on current standards of assay precision should be used to define the sensitivity of cTnT as biochemical evidence of ischaemic cardiac damage and as an indicator of mortality risk. This level is likely to be between 0.03 and 0.1 microg/l.

Aged↗
PubMed2005

One stage treatment of parathyroid cancer.

AIM: To review the methods of treating parathyroid cancer in our series and report successful use of intraoperative frozen section to enable one stage surgical management. METHOD: Seven cases of parathyroid cancer presented from 1991-2002. The presenting features, diagnosis and treatment are presented. They are separated into two groups based on method of referral and treatment. RESULTS: Patients presented with symptoms of hypercalcaemia. Median corrected calcium was 3.49 mmol/l. Parathyroid hormone levels were raised in seven of eight cases, range 14.5-495 pmol/l. A high index of pre-operative suspicion and use of frozen section enabled a one step surgical procedure. Recurrence was impossible to treat successfully. Radiotherapy appeared successful for residual disease. CONCLUSION: A high pre-operative index of suspicion for parathyroid carcinoma with use of frozen section at time of operation permits an optimal one step surgical procedure by en bloc resection followed by central lymph node excision. In cases where diagnosis has been made post-operatively radiotherapy may be beneficial.

Adult↗
PubMed2005

Cast wedging for orthopaedic surgeons!

The use of cast wedging is decreasing. Previous described methods are complicated, using geometric calculations that can be confusing and difficult to remember. We describe a very simple method we use routinely that involves a pen, a piece of paper and a pair of scissors only, without the need to calculate or measure angles.

Casts, Surgical↗
PubMed2004

Multivariate head injury threshold measures for various sized children seated behind vehicle seats in rear impacts.

Government recommendations to place children into the rear areas of motor vehicles to avoid airbag induced injuries have been complicated by the fact that most adult occupied front seats will collapse into the rear area during rear-impacts, and thus pose another potentially serious injury hazard to rear-seated children. Many variables affect whether or not a front seat occupant will collapse into the rear child, and whether that interaction could be injurious to the child. For instance, the severity of rear impact, coupled with front and rear occupant sizes (mass and stature), and the level of front seat strength, all interrelate to influence whether or not a rear seated child is likely to be impacted and possibly injured. The most common types of child injuries in these instances are head and chest injuries. In this study, a "high-low" experimental method was employed with a multi-level "factorial analysis" technique to study "multivariate" biomechanics of child head injury potential determined from rear-seated 3 and 6 year-old child surrogates in different types of vehicle bodies mounted to a sled system. The sled-buck systems were towed rearward into crushable barriers that matched the crash pulses of the vehicle types being tested. Various sizes of adult surrogates (i.e. 50 kg up to 110 kg), seated in both the "typical" low strength "single recliner" collapsing type front seat (i.e. 3.2 kN) and a much stronger "belt-integrated" seat design (i.e. up to 14.5 kN), were tested in the two different "sled body-buck" set-ups at various impact levels (i.e. 22.5 to 50 kph). One set-up used a popular minivan vehicle body with "built-in booster" seats for the 3 year-old. The other used a 4-door family sedan vehicle body with the 6 year-old in a standard rear bench seat. The parameters of the tests enabled the experimental data to be combined into polynomial "head injury" functions of the independent variables so the "likelihood" of rear child head-injury potential could be "mapped" over ranges of the key parameters. Accident cases were compared with predictions to verify the methodology.

Accidents, Traffic↗
PubMed2004

Thyroxine unmasks Addison's disease.

UNLABELLED: Patients with primary hypothyroidism may also have other underlying associated endocrinopathies, which are important to exclude. A 15-y-old girl presented with clinical biochemical evidence of hypothyroidism. CONCLUSION: Thyroxine replacement unmasked Addison's disease and precipitated an acute adrenal crisis. On physiological steroid replacement therapy, her "hypothyroidism" resolved.

Addison Disease↗
PubMed2003

Respiratory and fecal shedding of porcine respiratory coronavirus (PRCV) in sentinel weaned pigs and sequence of the partial S-gene of the PRCV isolates.

Porcine respiratory coronavirus (PRCV), a spike (S) gene deletion mutant of Transmissible gastroenteritis virus (TGEV), causes mild or subclinical respiratory infections in pigs. The shedding of PRCV/TGEV was studied at different days post-arrival in fecal and nasal swabs from PRCV/TGEV seronegative sentinel pigs introduced into a PRCV seropositive herd with questionable TGEV serology and diarrhea. Nasal shedding of PRCV was detected in 57% and 63% of samples by nested-RT-PCR and cell culture immunofluorescence (CCIF), respectively. However fecal shedding of PRCV was detected in 37% of the samples by nested-RT-PCR and 19% by CCIF. Four respiratory and 5 fecal PRCV strains were isolated in swine testicle cells including nasal/fecal PRCV pairs (isolated at the same time) from 3 pigs. Comparison of nasal/fecal PRCV pairs from individual pigs revealed different deletions in the spike (S) gene (648 or 681 nt) in 2 pairs and a consistent change in nt 790/791 (aa T to V) for all pairs. In preliminary studies, inoculation of gnotobiotic pigs with each plaque-purified pair of the nasal and fecal PRCV isolates, revealed no clinical disease but different tropisms. The nasal isolate was shed both nasally and in feces, but the fecal isolate was shed only marginally in feces, and not nasally. Our results show that nested-RT-PCR was as sensitive as CCIF for PRCV detection in nasal swabs, but was more sensitive than CCIF for PRCV detection in fecal samples; alternatively PRCV shed in feces was more labile with loss of infectivity. The S-gene sequence differences found between the fecal and respiratory PRCV isolates may influence their tissue tropism. These new PRCV isolates should be useful to understand the molecular basis of coronavirus tropism and evolution in infected swine.

Animals↗
PubMed2003

Protection and antibody responses to oral priming by attenuated human rotavirus followed by oral boosting with 2/6-rotavirus-like particles with immunostimulating complexes in gnotobiotic pigs.

We evaluated antibody responses and protection induced by attenuated Wa human rotavirus (AttHRV) and VP2/6-rotavirus-like particles (VLP), 100 or 250 microg/dose, with immunostimulating complexes (ISCOM) (VLP/ISCOM) each given orally, alone or sequentially to gnotobiotic pigs. The AttHRV-VLP 250 microg/ISCOM and three-dose-AttHRV (AttHRV3x) groups had significantly higher serum IgA, IgG and intestinal IgA antibody titers to HRV pre-challenge than the three-dose-VLP 100 microg/ISCOM group (VLP/ISCOM3x) and controls (diluent/ISCOMmatrix). Protection rates against viral shedding and diarrhea were highest in the AttHRV-VLP250 microg/ISCOM and AttHRV3x groups, lower in the AttHRV-VLP 100 microg/ISCOM group, with no protection in the VLP/ISCOM3x group and controls. Thus, VLP/ISCOM boosted antibody titers and protection after priming with AttHRV.

Adjuvants, Immunologic↗
PubMed2003

Quality control in urodynamics: a review of urodynamic traces from one centre.

OBJECTIVE: To investigate quality control in our unit and to enable other units to compare their results, as experience from central reviews of urodynamic traces for multicentre trials has suggested that poor quality control is common. PATIENTS AND METHODS: All consecutive male urodynamic tests conducted over 1 year were reviewed. A list of criteria to assess the quality of the records was devised, based upon International Continence Society guidelines on "good urodynamic practice", and on other sources. Eligible traces were analysed for aspects of quality control, e.g. baseline pressures and coughs to test pressure transmission. The data were analysed to establish how often quality criteria were met, and identify areas for improvement. RESULTS: In 100 eligible traces, the baseline detrusor pressure was 0-10 cmH2O in 86, and - 5 to +10 cmH2O in 94%. Baseline intravesical and abdominal pressure were 30-50 cmH2O in 68% and 73% of cases, respectively. Coughs were present before filling in 94%, during filling in 95%, before voiding in 72% and after voiding in 87% of cases. The cough-test frequency was sufficient in 30% of traces. In 11 the intravesical pressure line fell out during voiding. CONCLUSION: Most of the traces assessed met the quality criteria defined, but significant defects were not uncommon. Some of the problems identified suggest areas of urodynamic technique which should be studied in more detail. We intend to modify our quality control practices, and hope to show an improvement on re-audit. We hope that other urodynamic departments will be encouraged to review their practice, and we aim to improve our results.

Adult↗
PubMed2003

The biochemical detection of biliary etiology of acute pancreatitis on admission: a revisit in the modern era of biliary imaging.

INTRODUCTION: Compared with traditional radiologic methods for the detection of cholelithiasis, early transient hypertransaminasemia had provided a useful prediction of biliary etiology in patients with acute pancreatitis. AIM: To investigate whether this application remains valid in the modern era of imaging for microlithiasis. METHODOLOGY: The biochemical detection (LFT) of cholelithiasis was based on an increase in serum alanine transaminase of >or=80 IU/L (normal range, 0-45 IU/L) within 24 hours of admission. We have taken the collective findings of abdominal ultrasound (USS), endoscopic ultrasound (EUS), and postmortem examination to represent the denominator for the diagnosis of cholelithiasis against which comparison with LFT was made. RESULTS: Of 68 patients with acute pancreatitis who were treated between October 2000 and December 2001, cholelithiasis was the etiological factor in 44 patients (65%). EUS detected microlithiasis in 5 of 10 patients examined. The etiology remained idiopathic in 3 patients (4.4%). The sensitivity, specificity, and positive and negative predictive values for USS were 86%, 100%, 100%, and 80% respectively; for LFT, they were 91%, 100%, 100%, and 86%; and for USS and LFT combined, they were 98%, 100%, 100%, and 96%, respectively. CONCLUSIONS: In patients with acute pancreatitis, the biochemical analysis within 24 hours of admission provided a simple, rapid, and more accurate prediction of cholelithiasis than USS. The combination of LFT and USS detected or excluded a biliary etiology in almost all patients.

Acute Disease↗
PubMed2002

Familial frontotemporal dementia associated with a novel presenilin-1 mutation.

We report a kindred with three cases of dementia. The proband presented with forgetfulness and personality changes at age 56, followed shortly thereafter by behavioral dyscontrol, hyperphagia, hypersexuality, delusions, illusions, disinhibition and double incontinence. Neuroimaging studies were consistent with frontotemporal dementia (FTD). In one allele, an arginine insertion at codon 352 in the presenilin 1 (PSEN1) gene was identified; no mutation was identified in the amyloid precursor protein or tau genes. We conclude that the clinical features of the Kluver-Bucy syndrome and FTD can be associated with PSEN1 mutations. Furthermore, presenilin analyses may be helpful to characterize kindreds with familial dementing illnesses regardless of the phenotype, particularly if no tau mutation is present.

Dementia↗
PubMed2001

The whereabouts of a morphogen: direct evidence for short- and graded long-range activity of hedgehog signaling peptides.

Sonic Hedgehog (Shh) and Indian Hedgehog (Ihh) are members of the Hedgehog (Hh) family of signaling molecules known to be involved in embryonic patterning and morphogenesis. The Hh proteins undergo an autocatalytic cleavage to yield an N-terminal and a C-terminal peptide, with the signaling capacities confined to the N peptide. Drosophila Hh-N has been shown to act via both short- and long-range signaling. In vertebrates, however, attempts to directly demonstrate Shh (SHH) or Ihh (IHH) proteins at a distance from producing cells have been largely unsuccessful. Furthermore, the fact that the Hh N peptides occur in a cholesterol-modified, membrane-tethered form is not easily reconciled with long-range signaling. This study used optimized immunohistochemistry combined with tissue separation and biochemical analyses in vivo and in vitro to determine the range of action of SHH and IHH in the mouse embryo. In all embryonic structures studied, we detect signaling peptides in producing cells, but we also find that ligands move over considerable distances depending on the tissue. These data provide direct evidence for the presence of Hedgehog signaling peptides in target compartments, suggesting a direct long-range action without a need for secondary mediators. Visualization of Hedgehog proteins in target tissues was achieved only under conditions that allowed proteoglycan/glycosaminoglycan (PG/GAG) preservation. Furthermore, we show that induced changes of the composition of PG/GAG in the tooth alter SHH signaling. These data suggest a crucial role for PG/GAGs in Hedgehog movement.

Animals↗
PubMed2001

Dishevelled regulates the metabolism of amyloid precursor protein via protein kinase C/mitogen-activated protein kinase and c-Jun terminal kinase.

Alzheimer's disease (AD) is a disorder of two pathologies: amyloid plaques, the core of which is a peptide derived from the amyloid precursor protein (APP), and neurofibrillary tangles composed of highly phosphorylated tau. Protein kinase C (PKC) is known to increase non-amyloidogenic alpha-secretase cleavage of APP, producing secreted APP (sAPPalpha), and glycogen synthase kinase (GSK)-3beta is known to increase tau phosphorylation. Both PKC and GSK-3beta are components of the wnt signaling cascade. Here we demonstrate that overexpression of another member of this pathway, dishevelled (dvl-1), increases sAPPalpha production. The dishevelled action on APP is mediated via both c-jun terminal kinase (JNK) and protein kinase C (PKC)/mitogen-activated protein (MAP) kinase but not via p38 MAP kinase. These data position dvl-1 upstream of both PKC and JNK, thereby explaining the previously observed dual signaling action of dvl-1. Furthermore, we show that human dvl-1 and wnt-1 also reduce the phosphorylation of tau by GSK-3beta. Therefore, both APP metabolism and tau phosphorylation are potentially linked through wnt signaling.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Schwalbe line's cell in the normal and glaucomatous dog.

OBJECTIVE: The canine iridocorneal angle contains an operculum, which is similar to that in nonhuman primates and consists of a peripheral extension of the inner cornea that overlies the anterior-most portion of the corneoscleral trabecular meshwork. This region contains cells, the Schwalbe line's (SL) cells, that have been found to have secretory and epithelial characteristics. This region of the iridocorneal angle represents the nonfiltering portion and becomes altered early during spontaneous glaucoma in the Beagle. The present study describes the SL cell for the first time in the dog and changes associated with canine primary open angle glaucoma. PROCEDURES: The iridocorneal angles from 18 Beagles with inherited glaucoma (3 months-8 years old) and 17 normal, age-matched Beagles were placed in 10% buffered formalin for light microscopic evaluation, or 2.5% glutaraldehyde for ultrastructural evaluation. Using at least three fields from each region of the iridocorneal angle (opercular, corneoscleral, and uveal) at x 1000 magnification, trabecular cell nuclei were counted. RESULTS: The operculum in the canine iridocorneal angle consisted of the peripheral extension of the corneal endothelium and underlying anterior-most corneoscleral meshwork, having no direct contact with the angular aqueous plexus. The SL cells associated with operculum-retained epithelial morphology (polyhedral in shape with rER, Golgi apparatus, and secretory vesicles) in both normal, pre-and early glaucomatous dogs. In animals with moderate and advanced stages the SL cells often became less epithelial and secretory in appearance. The number of SL cells in normal dogs declined by approximately one-third by the end of their first year with gradual loss thereafter. In the glaucoma group the decline was more substantial and continuous through the first three years. CONCLUSIONS: The SL cell is morphologically a distinct cell type within the canine iridocorneal angle that is specifically associated with the nonfiltering portion of the corneoscleral trabecular meshwork. Changes in the SL cells of the glaucomatous dog occurred with regard to age and progression of the disease.

Animals↗