Winning payment for cognitive services: what works.
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Cognition↗
Biomedical subjects
S Scott
Publications and source records attributed to S Scott.
Liver resection for colorectal liver metastases.
The management of patients with colorectal liver metastases is still controversial. Recent evidence suggests benefit for resection of localized metastases within a single lobe of the liver. A series of 49 patients undergoing liver resection for localized liver metastases is presented. Resection involved right hepatectomy (23), left hepatectomy (8) and segmental excision (18). The median age was 62 (range 40-77). Patients have been followed for a period of up to seven years. The overall median survival was 24 months. The actuarial 3-year survival was 57.9%. There was no significant correlation of survival with the degree of differentiation or Dukes staging of the primary tumour. This series adds further weight to the evidence supporting resection in selected patients with colorectal liver metastases.
Adult↗
Transcriptional co-activation at the ansB promoters: involvement of the activating regions of CRP and FNR when bound in tandem.
Previous work with semi-synthetic promoters containing a single CRP binding site centred at 41.5 bp from the transcription start site has demonstrated enhanced transcription (synergism) when a second binding site, for CRP or FNR, is placed upstream at around -91 bp. The ansB promoter in Escherichia coli is co-activated in a co-dependent manner by one dimer each of CRP and FNR protein whose binding sites are at around -91 and -41 bp, respectively, from the transcription start site. Similarly, the homologous ansB promoter in Salmonella is co-activated by two dimers of CRP which function synergistically. The binding sites at the E. coli promoter have been changed by mutation to provide a number of active promoter derivatives carrying other combinations of FNR and CRP binding sites. The co-dependent versus synergistic interaction of these activators and their requirement for known activating regions have been examined. The results demonstrate that FNR can co-activate when located upstream at around -91 bp in combination with either FNR or CRP downstream. When FNR occupies the downstream site the promoter is co-dependent on an upstream activator, but not when CRP occupies this site. Activating region 1 in CRP (defined by substitutions at residue H159) and its putative equivalent in FNR (defined by substitutions at S73) are mainly required in the upstream activator; the putative equivalent in FNR of activating region 3 of CRP (defined by substitutions at G85 and K52, respectively) is mainly required in the dimer which binds downstream. Activating region 1 of FNR is required only in the downstream subunit of the upstream activator in a promoter which is co-dependent on two FNR dimers. These data suggest that both bound upstream and downstream activators interact with RNA polymerase to promote transcription, and that co-dependence is determined by the nature of the activator plus the promoter context.
Asparaginase↗
Infant mortality and famine: a study in historical epidemiology in northern England.
OBJECTIVE: To examine whether periodic variations in annual infant mortality were associated with malnutrition and the poor quality of the food supply available to the community. DESIGN: Retrospective study of historical epidemiology of infant mortality by time series analysis and family reconstitution of parish registers of burials and baptisms. SETTING: Penrith, Cumbria, England, 1557-1812. SUBJECTS: A total of 17,500 births during 1557-1812. RESULTS: This community in the Eden Valley, Cumbria, close to the Scottish borders, was living under marginal conditions with high mortality and low fertility. Clear oscillations in infant mortality synchronise with the oscillations in the wheat price index which is regarded as a measure of the availability of food to the community, and to pregnant and nursing mothers in particular. Input-output analysis showed that the relationship between the wheat price index (input) and infant mortality (output) was highly significant (p < 0.001). Events during the famine of 1623 have been analysed in detail: high wheat prices during pregnancy caused subsequent severe infant mortality but did not have indirect effects on the subsequent mortality of the surviving children over the age of 1 year. Non-stationary oscillations in neonatal and post neonatal mortality were strongly coherent (p < 0.001) with the wheat price index throughout the period. CONCLUSIONS: Infant mortality is particularly sensitive to famine and also to the quality of the food supply available to pregnant and nursing mothers. The lags between neonatal and post-neonatal mortalities and wheat prices, together with the analysis of the famine of 1623, support the hypothesis that neonatal mortality was related to malnutrition in pregnancy whereas post-neonatal mortality was primarily directly dependent on exogenous causes in the first year of life.
England↗
Blood pressure lowering by pioglitazone. Evidence for a direct vascular effect.
To examine potential mechanisms for the blood pressure-lowering action of the thiazolidinedione compound, pioglitazone (PIO), we studied the effects of the drug on blood pressure and insulin action in vivo and on vascular tissue in vitro. In vivo, PIO lowered blood pressure in fructose-fed and chow-fed rats to an extent that could not be explained by alterations in fasting plasma insulin or free magnesium concentrations or by alterations in whole-body insulin sensitivity. In vitro, PIO caused significant blunting of the contractile responses of aortic rings to NE, arginine vasopressin (AVP), and potassium chloride; the blunting of responses to NE was maintained after removal of the endothelium. To assess the potential importance of extracellular calcium to the vasodepressor effect of PIO, we measured contractile responses to NE in the absence of calcium, and then after acute restoration of calcium in the presence of NE. PIO had no effect on the contractile response in the absence of calcium. By contrast, PIO blunted by 42% the contractile response that occurred when the extracellular calcium supply was acutely restored in the presence of NE, suggesting that the blunting was mediated by blockade of calcium uptake by vascular smooth muscle. Such an effect was confirmed in cultured a7r5 vascular smooth muscle cells, which exhibited a brisk increase in intracellular calcium in response to AVP that was blocked by PIO in a dose-dependent fashion. Our data indicate that PIO has a direct vascular effect that appears to be mediated at least in part by inhibition of agonist-mediated calcium uptake by vascular smooth muscle. The direct vascular effect may contribute to the blood pressure-lowering actions of PIO in vivo, because that effect could not be explained by alterations in whole-body insulin sensitivity.
Animals↗
Infants and young children with cystic fibrosis have high levels of serum sialyl Lewis(a) antigen.
Previous studies suggest that serum levels of the mucin-associated sialyl Lewis(a) (Le(a)) antigen (NeuAC alpha 2-3 Gal beta 1-3 [Fuc alpha 1-4]GlcNAc beta 1...) correlate with the pulmonary status of cystic fibrosis (CF) patients who have Le(a) or Lewis(b) blood types and can form the antigen. However, there is little information on serum sialyl Le(a) antigen levels in CF patients or normal children younger than 9 y. We measured serum antigen levels using the MAb 19-9 in normal term neonates, CF infants and young children, and infants and children who had bronchopulmonary dysplasia or asthma. The mean serum sialyl Le(a) antigen level of the CF patients was 46.7 U/mL, significantly above (p < 0.01) the mean levels of the three other groups. The mean serum sialyl Le(a) levels of the three non-CF groups were not significantly different from one another or from published normal values. We conclude that serum sialyl Le(a) antigen levels are elevated early in CF, but are normal in asthma and bronchopulmonary dysplasia patients.
Carbohydrate Sequence↗
Parental perceptions of procedure-related distress and family adaptation in childhood leukemia.
Child and parental distress related to lumbar punctures and bone marrow aspirates and general family adaptation are evaluated in a cross-sectional study of children currently in treatment with leukemia in first remission (N = 70). A parental self-report measure developed for this study--the Perception of Procedures Questionnaire (PPQ)--yielded three factors: (a) parental satisfaction, (b) parental distress or involvement, and (c) child distress. Data from the PPQ showed high levels of both satisfaction and distress in the context of invasive procedures. Data from standardized measures of family adaptation demonstrated a range of functioning. Analyses by length of time since diagnosis indicated that parental distress remains stable over the course of treatment. The data are discussed with respect to the newly developed measure of parental procedures (the PPQ) and the need for research in this field that provides an integration of procedural distress with parent and family perceptions and adjustment.
Adolescent↗
Interleukin-1 beta regulates the expression of a leukocyte type of 12-lipoxygenase in rat islets and RIN m5F cells.
The leukocyte type of 12-lipoxygenase (12-LO) may play a role in inflammatory reactions in many cell types through the conversion of arachidonic acid to proinflammatory eicosanoids that include 12-hydroperoxyeicosatetraenoic acid and 12-hydroeicosatetraenoic acid. Previous studies demonstrating the presence of a functional 12-LO pathway in rat and human pancreatic beta-cells plus the recent cloning of a rat leukocyte type of 12-LO allowed us to evaluate whether inflammatory cytokines such as interleukin-1 beta (IL-1 beta) can regulate the beta-cell 12-LO enzyme pathway, thus providing a potential link between the cytotoxic effects of cytokines on pancreatic beta-cells and the proinflammatory effects of 12-LO products. We demonstrate that IL-1 beta induces 12-LO protein and messenger RNA (mRNA) expression in RIN m5F cells and 12-LO mRNA expression in rat islets. RIN m5F cells treated for 16 h with IL-1 beta (25, 50, and 100 ng/liter) showed a maximal 2-fold increase in the expression of a leukocyte form of 12-LO demonstrated by Western blots. A concomitant increase in 12-LO mRNA expression was seen at this time point using a highly sensitive competitive polymerase chain reaction assay. The increase in mRNA and protein expression was preceded by increased 12-LO pathway activity measured by a RIA for 12-S-HETE. Separate experiments using purified Sprague-Dawley rat islets also showed increased expression of 12-LO mRNA and enzyme activity in response to IL-1 beta. These results demonstrate that IL-1 beta can up-regulate 12-LO expression and activity in rat beta-cells.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
Recurrent pelvic support defects after sacrospinous ligament fixation for vaginal vault prolapse.
BACKGROUND: Multiple studies have shown sacrospinous ligament fixation to be highly effective therapy for vaginal vault prolapse. Several authors have suggested that the marked vaginal retroversion subsequent to sacrospinous ligament fixation may predispose to recurrent pelvic support defects in the anterior fascial segment, resulting in cystocele or urethrocele, or both. STUDY DESIGN: Thirty-six patients, 46 to 86 years of age, were examined at six weeks postoperatively and at long-term follow-up evaluation 15 to 79 months (median of 42 months) after sacrospinous ligament fixation and repair of associated pelvic support defects. The examinations, by an unbiased examiner, were done to identify and grade recurrent pelvic support defects. RESULTS: At the six week postoperative visit, one patient had a small enterocele, and none of the patients demonstrated vaginal vault prolapse. At the long-term follow-up visit, 33 (92 percent) of the patients had cystoceles, six (17 percent) had rectoceles, two (6 percent) had enteroceles, and three (8 percent) demonstrated recurrent vaginal vault prolapse. Most cystoceles were small and asymptomatic. CONCLUSIONS: A high rate of success in the treatment of prolapse of the upper vagina by sacrospinous ligament fixation was observed. Pelvic support defects at long-term follow-up evaluation occurred more commonly in the anterior fascial segment. Retroversion and fixation of the upper vagina predisposes the anterior fascial segment to excess pressure and a higher incidence of cystocele than could be attributed to the effects of aging and menopause.
Aged↗
Planning operating departments: another viewpoint.
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Hospital Design and Construction↗
Long-term effects of neuromuscular rehabilitation of chronic facial paralysis.
Although chronic facial dysfunction can be improved with neuromuscular biofeedback therapy, it is uncertain whether this improvement is maintained after such therapy ends, or whether post-therapy, home exercise programs optimize this improvement. We aimed to clarify these issues. Post-therapy facial function, in 38 previously treated patients, was blindly assessed using the House grading system, 1 to 41 months after ending therapy. Results were compared with pre-therapy function. It was found that post-therapy function was better than pre-therapy function in most patients (40%), it was worse in some (26%), and was unchanged in the rest. This surprising result occurred because, although most patients who recently stopped therapy (1 to 6 mo) had improved significantly, the longer other patients were out of therapy, the more they had tended to deteriorate, particularly those who had been practicing. Results suggested that unsupervised, post-therapy, home exercise programs may be detrimental, and that new post-therapy programs may be required to maintain the benefits of regular therapy.
Adolescent↗
Modelling the different smallpox epidemics in England.
Time series analysis has revealed two different patterns of smallpox epidemics in Britain in the seventeenth and eighteenth centuries: in large conurbations (exemplified by London) the disease was endemic whereas medium-sized rural towns (exemplified by Penrith, Cumbria) suffered from 5 year epidemics with no cases of smallpox in the inter-epidemic years. The oscillations (epidemics) persisted for over 150 years and it is suggested that both systems were pumped up by regular fluctuations in susceptibility (delta beta). Modelling suggests that: (i) the natural frequency of oscillations in large cities is two years and the system is pumped up by a 1 year, seasonal input; (ii) it takes five years to build up a pool of susceptibles in medium-sized towns by new births and epidemics are then triggered by a 5 year input. The equations represent a system that has two components, a basic linear element with the remainder of the system being nonlinear; modelling a progressive increase in delta beta in London illustrates theoretically how a predominantly linear response changes to a nonlinear response and ultimately to chaos. A variation in susceptibility is a theoretical condition for inducing chaos; the undriven system cannot become chaotic. Modelling populations of progressively increasing size/density and applying a 1 year or 5 year sinusoidal oscillation in delta beta illustrates the fundamental distinction in the response of medium-sized rural towns and large cities.
Child↗
Reagents for the preparation of two oligonucleotides per synthesis (TOPS).
In order to increase the efficiency of use of automated DNA synthesizers (i.e. the number of oligomers prepared per day), we have devised and prepared novel phosphoramidite reagents that contain a linking group which, while stable under the normal synthesis conditions, is cleaved under basic conditions. When one of these linkers is introduced at the desired position in the synthesis of an oligonucleotide, subsequent detritylation enables the synthesis of a second oligonucleotides sequence upon the first. During deprotection of the oligonucleotide with ammonium hydroxide, the chain is cleaved at either side of the points of introduction of the novel reagent, generating two oligonucleotides free in solution. These reagents are of particular use in applications where oligomers are used in pairs (such as PCR, chemical synthesis of genes etc.) and means that an automated synthesis facility can be used more efficiently, without the need for operator intervention, after the working day is over.
Amides↗
Evidence that pioglitazone increases intracellular free magnesium concentration in freshly isolated rat adipocytes.
Pioglitazone is one of a new class of oral agents being developed as antidiabetic agents which can increase insulin sensitivity, reduced blood pressure and improve abnormalities in lipid metabolism. The mechanism of action of pioglitazone is not known. Increasing evidence suggests that magnesium can play an important role in regulating glucose homeostasis and vascular tone. To clarify a potential mechanism of pioglitazone action we determined the effects of pioglitazone on intracellular free magnesium concentration in freshly isolated rat adipocytes. Concentrations of pioglitazone as low as 300 nM markedly increased the free magnesium concentration in the adipocytes. Pioglitazone action was selective for magnesium since intracellular free calcium concentration was not altered. These new data suggest that a potentially important mechanism explaining the metabolic and vascular actions of these new anti-diabetic agents is increasing free magnesium concentration in target tissues.
Adipocytes↗
The Ste-Justine Adolescent Idiopathic Scoliosis Cohort Study. Part I: Description of the study.
OBJECTIVES: This study determined the impact of adolescent idiopathic scoliosis (AIS) on health and well being in adulthood by comparing AIS subjects, more than 10 years after referral, to non-AIS subjects according to perceived health status, physical activity, fitness, reproductive health, respiratory condition, and back and neck pain. This paper describes the cohort, the design of the study, and response rates. STUDY DESIGN: The study was designed as a comparative retrospective cohort study. A total of 2,092 patients referred for AIS to Ste-Justine Hospital, Montreal, Quebec, between 1960 and 1979 were identified. A population-based control group was selected in 1989-90 by randomly telephoning persons in Quebec. The control group was approximately frequency-matched to the AIS cohort according to age group and broad geographic region of current residence. METHODS: Patients with adolescent idiopathic scoliosis were traced, and a self-administered questionnaire was sent by post in 1989 to subjects whose addresses were found. Identical questionnaires were sent to subjects in the control group. RESULTS: Seventy-one percent of the cohort (1,476 subjects) returned questionnaires in 1989. Subjects who did not respond to the questionnaires were similar to those who did complete the questionnaires on a number of key factors, except that lower response rates were observed for subjects with scoliotic curves under 20 degrees. The control group consisted of 1,755 subjects (55% response rate). It was similar to the general Quebec population and to the AIS cohort on a number of important sociodemographic factors. CONCLUSION: Comparisons on health outcomes between the two study groups should not be affected by differential patterns of selection or response.
Adolescent↗
The Ste-Justine Adolescent Idiopathic Scoliosis Cohort Study. Part III: Back pain.
OBJECTIVES: This study determined health and well being of persons with adolescent idiopathic scoliosis (AIS) more than 10 years after referral. This communication will present results related to back pain. STUDY DESIGN: This study was designed as a comparative retrospective cohort study. Subjects referred for AIS between 1960 and 1979 to a large pediatric hospital in Montreal, Quebec, were entered into the cohort. A population-based control group was selected from the general population of Quebec using a telephone survey. METHODS: Back pain was assessed by postal questionnaires administered, in 1990, to the AIS cohort and to the control group. Most outcomes were ordinal and, thus, odds ratios were estimated using ordinal regression while adjusting for potential confounding factors. RESULTS: Among the 1,476 AIS subjects responding, 73% experienced one or more episodes of back pain in the past year, significantly more than the 1,755 controls (56%); for current back pain, these proportions were also significantly different: 44% for AIS subjects and 24% for controls. In comparison to controls, AIS subjects reported pain that was more intense, continuous, generalized throughout the back, and radiating into the extremities. AIS subjects were also more restricted in many usual daily activities. Little variability was observed in the prevalence of current back pain and back pain in the past year according to treatment and degree of curvature. Difficulty with managing pain, lifting, walking, and socializing was, however, associated with severity. The results of this study suggest that back pain is responsible for a considerable amount of disability and handicap in later life. Health professionals involved with the management of persons with AIS need to consider this important outcome and need to put in place procedures for the identification, investigation, prevention, and treatment of back pain.
Activities of Daily Living↗
The Ste-Justine Adolescent Idiopathic Scoliosis Cohort Study. Part IV: Surgical correction and back pain.
OBJECTIVES: This study determined whether the prevalence, nature, and consequences of back pain in adulthood among persons who underwent Harrington rod instrumentation was related to the number of vertebrae fused, distal level of hook insertion, and degree of correction. STUDY DESIGN: This study was designed as a comparative retrospective cohort study. Subjects referred for AIS between 1960 and 1979 to a large pediatric hospital in Montreal, Quebec, were entered into the cohort. A population based control group was selected from the general population of Quebec using a telephone survey. METHODS: Back pain was assessed by postal questionnaire administered in 1990. Data was analyzed using two multivariate regression models: relative risk regression for dichotomous outcomes and ordinal regression for outcomes measured on an ordinal scale. RESULTS: Among the 723 AIS subjects who had surgery at Ste. Justine's Hospital, 555 completed the questionnaire on back pain. Overall, 73% of patients treated surgically reported back pain in the past year. Proportions varied little by presurgery characteristics or by degree of surgical correction. The distal level of fusion did not influence, in any consistent way, the occurrence of back pain in later life nor the degree of disability associated with back pain. This study does not provide any evidence that extending the level of fusion down even as far as L4 will increase the prevalence of back pain in adulthood.
Adolescent↗
The Ste-Justine Adolescent Idiopathic Scoliosis Cohort Study. Part II: Perception of health, self and body image, and participation in physical activities.
OBJECTIVES: This study determined the health and well being of persons with adolescent idiopathic scoliosis (AIS) more than 10 years after referral. This communication will present results related to the perception of health, self and body image, and difficulty with selected physical activities. STUDY DESIGN: The study was designed as a comparative retrospective cohort study. Subjects referred for AIS between 1960 and 1979 to a large pediatric hospital in Montreal, Quebec were entered in the cohort. A population-based control group was selected from the general population of Quebec at the time of survey. METHODS: Health outcomes were assessed by a postal questionnaire administered to the AIS cohort and to the control group. Most outcomes were ordinal and, thus, odds ratios were estimated using ordinal regression while adjusting for potential confounding factors. RESULTS: AIS subjects, particularly those who were surgically treated, had a significantly higher prevalence of self-reported arthritis. Scoliosis subjects perceived themselves to be less healthy than other persons the same age and, particularly among women, scoliosis subjects had a poorer perception of body image, and had more physician visits and days ill than control subjects. In addition, male and female AIS subjects had more difficulty with physical activities. This rather negative perception of health could be a result of actual illness or a result of more concern about illness. Nevertheless, they had a more positive perception of self and appeared to be able to cope with their affliction and disfigurement in a positive way.
Adolescent↗