Delays in stroke referrals.
Assessment of acute stroke by hospital physicians will have to speed up if we are to expect referral to hospital and computed tomography (both previously targets of criticism) to improve.
Acute Disease↗
Biomedical subjects
S Lewis
Publications and source records attributed to S Lewis.
The prevalence of asthma symptoms, bronchial hyperresponsiveness and atopy in New Zealand adults.
AIMS: To examine the prevalence of asthma symptoms, bronchial hyperresponsiveness (BHR) and atopy in a random population sample of New Zealand adults. METHODS: A random sample of 2004 adults, aged 20-44 years, in Hawkes Bay, Wellington and Christchurch, were selected from respondents to a one-page respiratory screening questionnaire and invited to take part in further testing. Subjects attending the testing centres' laboratories underwent a detailed respiratory symptom questionnaire, Phazet testing to eleven common allergens, blood samples for total and specific IgE, and measurement of bronchial hyperresponsiveness. Subjects who did not wish to participate were encouraged to complete the questionnaire by telephone. RESULTS: A participation rate of 67% (1257 of 1877 eligibles) was achieved. We found a high prevalence for all measures of asthma in the previous 12 months: wheezing was reported by 28.5%, waking with shortness of breath by 7.7%, a physician diagnosis of asthma by 15.9% and asthma medications were used by 8.5%. Bronchial hyperresponsiveness was found in 24.9%, atopy in 34.8% and elevated serum IgE levels in 30.5%. Asthma symptoms (in the past 12 months) and atopy decreased with increasing age, whereas bronchial hyperresponsiveness increased with age. Females reported higher prevalences of waking with coughing (45.9%), nasal allergies (43.5%) and skin allergies (48.8%) compared to males (30.5%, 31.9% and 37.0%, respectively). There were no significant regional differences. CONCLUSIONS: Asthma symptoms, bronchial hyperresponsiveness and atopy are all common in adult New Zealanders. Their prevalence is associated with age, gender and current smoking but there are no significant regional differences between Hawkes Bay, Wellington and Christchurch.
Adult↗
Palindromic DNA and genome stability. Further studies.
Unusual DNA structures promote genetic instability. One such example is hairpin DNA, which can form from palindromic sequences and triplet repeats, and is also a characteristic intermediate in V(D)J recombination. We previously found that a large 15.3-kb palindrome that was introduced as a transgene into the mouse germline was highly unstable. Although it could be transmitted, the transgene was found to be rearranged in up to 56% of the progeny, and rearrangement events often involved deletion at the center of symmetry. Here, the fine structure of centrally deleted palindromes was sampled by analysis of recombinant junctions isolated from testes DNA, providing further evidence for a model, previously proposed, that accounts for such deletions on the basis of a hairpin-tip nicking activity. In addition to central deletions, gene conversion events were also elevated in the transgenic palindrome. We have now analyzed instability in two mouse sublines in which (as a result of inversion) the transgenic palindrome had been shortened to 4.2 kb. In these sublines, the transgene was still subject to both rearrangement and gene conversion events at a high frequency, similar to the original 15.3-kb palindrome. Recombination was not limited to the sequences constituting the inverted repeat, but was seen to include sequences lying outside the palindrome. As discussed, the salient feature in all of these observations, a high level of genetic change associated with palindromic DNA, underscores the significance of hairpin DNA and hairpin-tip nicking in genome stability.
Animals↗
A pilot study evaluating the effectiveness of individual inpatient cognitive-behavioural therapy in early psychosis.
BACKGROUND: Recent research indicates that cognitive-behaviour therapy (CBT) can be effective in ameliorating persistent positive symptoms in chronic psychotic patients. The effectiveness of CBT in acute and recent-onset psychosis has been little explored, although a recent pilot study indicated that CBT could significantly improve recovery in acutely psychotic inpatients. METHOD: Short-term individual CBT was compared to supportive counselling/psychoeducation (SC) as an adjunct to standard inpatient hospital care and medication in 21 inpatients experiencing a recent-onset acute schizophrenic episode. RESULTS: Both groups showed significant reductions in Brief Psychiatric Rating Scale (BPRS) scores following treatment, although there were no group differences. Time to discharge did not differ significantly between the groups, although there was a greater variance for the SC patients. Two-year follow-up showed no significant differences between the groups, although the number of patients who relapsed, the number of relapses and the time to recurrence of psychotic symptoms was lower in the CBT group than the SC group. Interestingly, the time to readmission was shorter in the CBT group. CONCLUSIONS: CBT and SC are acceptable treatments for recent-onset acutely psychotic inpatients. A larger randomised controlled trial over multiple hospital sites is warranted.
Acute Disease↗
Macular translocation for subfoveal choroidal neovascularization in age-related macular degeneration: a prospective study.
PURPOSE: To conduct a prospective study of macular translocation in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. METHODS: In 10 eyes of 10 patients with subfoveal choroidal neovascularization and best-corrected visual acuity ranging from 20/50 to 20/800 (median, 20/111), the fovea was relocated by means of scleral imbrication, intentional retinal detachment with small posterior retinotomies, and partial fluid-air exchange. In two eyes, the choroidal neovascular membranes were removed at the time of macular translocation; in seven eyes they were photocoagulated in the postoperative period; and in one eye the membrane was removed during reoperation to unfold a macular fold. RESULTS: All 10 eyes were followed up for 6 months. The median postoperative foveal displacement was 1286 microm (range, 114 to 1,919 microm). In three eyes (30%), a foveal fold formed postoperatively requiring reoperation, with one of these eyes requiring a second reoperation for a rhegmatogenous retinal detachment. Best-corrected visual acuity improved in four eyes (median, 10.5 letters) and decreased in six eyes (median, 14.5 letters). The median change in visual acuity was a decrease of 5 letters. The final best-corrected visual acuity was 20/80 in two eyes, 20/126 in one eye, 20/160 in four eyes, 20/200 in one eye, 20/250 in one eye, and 20/640 in one eye. CONCLUSIONS: Our initial experience with limited macular translocation suggests that this surgical technique is unpredictable. However, in patients with subfoveal choroidal neovascularization from age-related macular degeneration, it offers the potential for improving visual function and may be associated with less loss of vision than the disease itself, if allowed to progress. Further refinements in surgical indications and technique are needed to make this procedure safer, more predictable, and more beneficial.
Aged↗
Now available onlineellipsis trends in pharmacological sciences
Explore the source record for details and available documents.
Journal Article↗
Confirmation of linkage in X-linked infantile spasms (West syndrome) and refinement of the disease locus to Xp21.3-Xp22.1.
The syndrome of infantile spasms, hypsarrhythmia, and mental retardation (West syndrome) is a classical form of epilepsy, occurring in early infancy, which is etiologically heterogeneous. In rare families, West syndrome is an X-linked recessive condition, mapped to Xp11.4-Xpter (MIM 308350). We have identified a multi-generation family from Western Canada with this rare syndrome of infantile spasms, seen exclusively in male offspring from asymptomatic mothers, thereby confirming segregation as an X-linked recessive trait. Using highly polymorphic microsatellite CA-repeat probes evenly distributed over the entire X chromosome, linkage to markers DXS7110, DXS989, DXS1202, and DXS7106 was confirmed, with a maximum LOD score of 3.97 at a theta of 0.0. The identification of key recombinants refined the disease-containing interval between markers DXS1226 and the adrenal hypoplasia locus (AHC). This now maps the X-linked infantile spasms gene locus to chromosome Xp21.3-Xp22.1 and refines the interval containing the candidate gene to 7.0 cM. Furthermore, this interval overlaps several loci previously linked with either syndromic or non-syndromic X-linked mental retardation (XLMR), including one recognized locus implicated in neuroaxonal processing (radixin, RDXP2). Collectively, these studies lend strong support for the presence of one or more genes intrinsic to brain development and function, occurring within the critical interval defined between Xp21.3-Xp22.1.
Chromosome Mapping↗
Indoor environment, atopy and the risk of the asthma in children in New Zealand.
The objective of this study was to examine the relationship between the indoor environment, atopy and asthma in 7-9-year-old children. Cases and controls were randomly selected from children who participated in the International Study of Asthma and Allergies in Childhood (ISAAC) in Wellington, New Zealand. Cases were children with a previous diagnosis of asthma and current medication use (n = 233) and controls were children with no history of wheezing and no diagnosis of asthma (n = 241). Information was recorded about the indoor environment during the first year of life and currently. Dust was sampled from floors and beds and Der p 1 and Fel d 1 measured using enzyme-linked immunosorbent assays. Skin-prick tests were performed with eight common allergens. Sensitization to Dermatophagoides farinae (OR = 3.19; 95% CI 1.74-5.84), Dermatophagoides pteronyssinus (OR = 2.06; 95% CI 1.16-3.65) and cat (OR = 3.89; 95% CI 1.06-14.30) were independently associated with current asthma. The use of a sheepskin in the first year of life (OR = 1.91; 95% CI 1.11-3.33) was also independently associated with current asthma but current Der p 1 levels showed no association with current asthma. Exposures in early life may be more important than current exposures in determining asthma at age 7-9 years. Prospective studies are needed in New Zealand to determine the relative importance of early life exposures to Der p 1 and other risk factors for asthma.
Air Pollution, Indoor↗
The work-family research agenda in changing contexts.
This article argues that research on the work-family interface has evolved against a backdrop of dramatic and ongoing social and workplace change and must continue to reflect current and future context. The article overviews current trends that have implications for work and family and considers some possible future scenarios. It identifies a number of research areas and questions that build on previous theoretical and practical developments in the work-family field and reflect current trends. It is argued that questions about the well-being and sustainability of workplace human resources, of families in their diverse forms, and of communities are of overriding significance for the work-family research agenda, particularly if current trends continue unabated.
Family Relations↗
Histological progression during short-term follow-up of patients with chronic hepatitis C virus infection.
Assessment of prognosis from hepatitis requires liver histology. When the fibrosis stage is known, and if the fibrosis progression rate can be established, time to development of cirrhosis can be calculated. The fibrosis progression rate can be calculated from a single biopsy when duration of infection prior to biopsy is known. Sequential biopsies can also be examined. In this work, we studied histological activity and fibrosis stage in liver biopsies of 157 hepatitis C virus (HCV)-infected patients, including 92 for whom the approximate duration of infection was known. The mean fibrosis progression rate was 0.09 units per year, and was not influenced by mode of infection or viral genotype. Forty-six patients who had very mild histological changes in the initial biopsy underwent repeat biopsy 2 years later (with no intervening anti-viral treatment). Comparison of paired biopsies confirmed a tendency to histological progression and increasing hepatic fibrosis (mean, 0.15 fibrosis units per year). A normal baseline alanine aminotransferase (ALT) value was associated with slow fibrosis progression before baseline biopsy and between biopsies. These data do not differ from published cross-sectional and longitudinal studies, and suggest that histological progression will be observed during follow-up of most patients, including those with mild histological changes at time of initial assessment.
Adult↗
The association of visual field deficits and visuo-spatial neglect in acute right-hemisphere stroke patients.
BACKGROUND: Visuo-spatial neglect (VSN) after stroke is associated with a poor prognosis for rehabilitation. The co-existence of a visual field deficit (VFD) with VSN may be associated with impaired visuo-spatial functioning and thereby poor functional outcome. OBJECTIVE: To determine whether the presence of a VFD (i) exacerbates VSN and (ii) influences recovery of VSN. METHODS: A prospective study of consecutive acute (<7 days), right-hemisphere stroke patients who were able to undergo detailed assessment of visuo-spatial functioning and visual fields. Clinical assessment and a standardized neuropsychological test was administered by one observer, followed by independent assessment of visual fields by a second observer. Patients were followed up for 12 weeks with 4-weekly re-assessments. RESULTS: 44 consecutive patients (23 women) with a first in a lifetime, acute hemisphere stroke were recruited. Twenty had VSN and VFD, seven VSN only, one VFD only and 17 had normal visual fields and no neglect. The finding of a VFD was significantly associated with the presence of VSN (P<0.0001). Patients with both VFD and VSN had a significantly lower score on the behavioural inattention test. One month post-stroke, this difference was no longer significant. Recovery of VSN and VFD was maximal in the first month, however VSN recovery continued for up to 12 weeks. Patients with VSN and a VFD on admission had a greater mortality at 1 and 3 months. CONCLUSION: The presence of a VFD does appear to exacerbate neglect in the acute stroke patient; this effect is no longer seen after 1 month. Recovery of VSN continues independent of a VFD. Patients with neglect and a VFD have an increased mortality, probably because of greater neurological impairment.
Acute Disease↗
Growth curves and survival characteristics of the animals used in the Biomarkers of Aging Program.
The collaborative Interagency Agreement between the National Center for Toxicological Research (NCTR) and the National Institute on Aging (NIA) was aimed at identifying and validating a panel of biomarkers of aging in rodents in order to rapidly test the efficacy and safety of interventions designed to slow aging. Another aim was to provide a basis for developing biomarkers of aging in humans, using the assumption that biomarkers that were useful across different genotypes and species were sensitive to fundamental processes that would extrapolate to humans. Caloric restriction (CR), the only intervention that consistently extends both mean and maximal life span in a variety of species, was used to provide a model with extended life span. C57BI/6NNia, DBA/2JNia, B6D2F1, and B6C3F1 mice and Brown Norway (BN/RijNia), Fischer (F344/NNia) and Fischer x Brown Norway hybrid (F344 x BN F1) rats were bred and maintained on study. NCTR generated data from over 60,000 individually housed animals of the seven different genotypes and both sexes, approximately half ad libitum (AL) fed, the remainder CR. Approximately half the animals were shipped to offsite NIA investigators internationally, with the majority of the remainder maintained at NCTR until they died. The collaboration supplied a choice of healthy, long-lived rodent models to investigators, while allowing for the development of some of the most definitive information on life span, food consumption, and growth characteristics in these genotypes under diverse feeding paradigms.
Aging↗
Adaptive role of caloric intake on the degenerative disease processes.
Carcinogenicity and aging are characterized by a set of complex endpoints, which appear as a series of molecular events. Many of these events can be modified by caloric intake. Since most of these processes determine an organism's ability to cope with various environmental stressors, it is not surprising that a relationship (in the presence of a constant nutrient density) exists between caloric intake and time-to-tumor and/or life span. Our studies have clearly shown that generally, the greater the caloric intake, the greater the body weight, the higher the incidence of spontaneous tumor occurrence, the greater the susceptibility to chemical carcinogens, and the shorter the life span. It is also recognized that variables other than body weight influence the life span and carcinogenesis. We have focused our attention on the questions of how and to what extent caloric intake modifies those homeostatic processes believed to be critical in determining the ability of an organism to cope with endogenous and exogenous stresses such as chemical, physical, and biological carcinogens. The response of an organism to its environment can be divided into four categories--physiological, metabolic, molecular, and cellular. We have found that, from a physiological perspective, decreasing caloric intake causes body temperature in rodents to be decreased by 0.5 to 1.8 degrees C and water consumption to be increased by 80%, as is running activity. However, metabolic output per gram of lean body mass is not altered. Reproductive capacity declines, whereas the ECG waveform is preserved as caloric intake decreases. Alterations in these and other physiological functions suggests that energy intake serves as a signal to up-regulate or down-regulate functions related to the flight-or-fight response observed in placental mammals. A number of key metabolic pathways are altered as a function of lowered caloric intake, even though the rate of food consumption per gram of lean body mass remains steady during body weight decreases caused by decreasing caloric intake. Pharmacological compartmentalization, however, is altered. As caloric intake declines, changes occur in the expression of a number of drug-metabolizing enzymes, with the most striking effect seen in sex-specific growth hormones and liver-dependent phase I and phase II enzymes. Additionally, oxidative stress (free-radical and mediated damage to macromolecules) appears to decrease as a function of reduced caloric intake. A number of molecular processes also change with changes in energy consumption. Our studies have shown that, regardless of the source and nature of DNA damage, DNA repair is better preserved and/or enhanced when caloric consumption decreases. In addition, the fidelity of DNA replication increases and oncogene expression is stabilized, P53 gene expression is increased, and apoptosis is elevated by up to 500% with decreased caloric intake. At the cellular level, cell proliferation is decreased in direct proportion to lower energy intake in some but not all tissues. Studies have also shown an enhancement in immune capacity, changes in IGF1, and accelerated rates of wound healing proportionate to declines in energy consumption. Our most recent findings, however, have shown that the benefits associated with decreases in caloric intake only occur in the presence of sufficient nutrient quality and density. In the absence of proper nutrition, however, sensitivity to carcinogens and toxic substances appears to be enhanced. These findings are supported by independent studies. These observations have led us to conclude that, in certain organisms, when caloric intake is decreased, there is an up-regulation of those processes that modulate the responses to a wide range of environmental stressors. This response allows for a better survival rate and a down-regulation of reproductive activity. It is our belief that, during periods of environmental stress, these systems may be essential to perpetu
Adaptation, Physiological↗
Chondroitin sulphation patterns in synovial fluid in osteoarthritis subsets.
OBJECTIVES: To determine concentrations of chondroitin sulphate (CS) disaccharides in knee synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or rheumatoid arthritis (RA), to test whether these variables differ between different diseases and subsets of OA. METHODS: OA was subdivided into large joint OA (LJOA), nodal generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition (CPA), with 25, 9, and 11 people in each subset respectively. The SF of 13 normal subjects was also volunteered for analysis along with 15 RA patients. Clinical assessment of inflammation (0-6) was undertaken on OA and RA knees. Concentrations of unsaturated CS disaccharides Deltadi6S and Deltadi4S were measured by capillary zone electrophoresis. RESULTS: Concentrations of Deltadi6S were lower in RA (5.90 ng/ml) and OA (13.24 ng/ml) fluids compared with normal (21.0 ng/ml) but no significant differences were seen between disease and normal fluids for Deltadi4S (about 4-6 ng/ml). The ratio of Deltadi6S:Deltadi4S were RA<OA<normal subjects (p<0.001 for all comparisons). The disaccharide concentration values along with the ratios are below. Higher Deltadi6S:Deltadi4S ratios were obtained for LJOA and CPA compared with NGOA. Uninflamed knees had lower concentrations of Deltadi6S than inflamed knees (p<0.01). In patients with bilateral samples, there were strong correlations between right and left knees for all SF variables. CONCLUSIONS: Altered ratios of CS sulphation patterns occur in OA and within OA subsets. These further justify considering NGOA as a subset with a different aetiopathogenesis.
Adult↗
Asthma prevalence and deprivation: a small area analysis.
STUDY OBJECTIVE: To investigate the relation between the prevalence of asthma symptoms in adults and deprivation in the area of residence. DESIGN: Two complementary surveys carried out between 1991-1993 yielding adult asthma symptom prevalence throughout New Zealand. Deprivation is measured by the NZDep91 index of deprivation for small areas. SETTING: New Zealand. PARTICIPANTS: A random sample of 25,042 adults aged 20-50 years. MAIN RESULTS: After controlling for possible confounding by age, gender, and ethnicity, the 12 month period prevalence rates of asthma in this representative sample of New Zealand adults are significantly higher in the three most deprived area categories than in the least deprived (tenth) category. The prevalence ratio for the most deprived category compared with the least deprived category is 1.29 with 95% confidence intervals (CI) 1.14, 1.47. There is a linear increase in asthma prevalence with increasing area deprivation (chi 2(1) = 32.20, p < 0.001). Independently, the rates are also 1.41 (95% CI 1.29, 1.54) times higher among Maori and 1.29 (95% CI 1.10, 1.52) times higher among the Pacific Island group than among the remaining, mostly European, respondents. CONCLUSIONS: The relation between asthma in adults and area deprivation is unlikely to be attributable to study biases or confounding. Further work should examine the possible role of modifiable deprivation factors in this relation.
Adolescent↗
Randomised controlled effectiveness trial of a needs-based psychosocial intervention service for carers of people with schizophrenia.
BACKGROUND: Family interventions are effective in reducing relapse in patients with schizophrenia, but there is little work demonstrating the effectiveness of the interventions in routine service settings. AIMS: To test the effectiveness of a needs-based family intervention service for patients recruited as out-patients and their carers, including those of low expressed emotion status. METHOD: Carers of out-patient schizophrenia sufferers selected only on illness history factors were randomly allocated to receive either family support alone or in combination with systematic psychosocial interventions based on an assessment of need. Delivery of family interventions attempted to involve the clinical team. RESULTS: Relapse outcomes were superior for family-treated patients at six-month follow-up, although most of the clinical and symptom patient variables assessed remained stable, as did measures of carer burden. CONCLUSIONS: The study demonstrated the effectiveness of family interventions in routine service settings. Problems with staff, patient and carer engagement and participation were identified.
Adult↗
PhosphoCREB and CREM/ICER: positive and negative regulation of proenkephalin gene expression in the paraventricular nucleus of the hypothalamus.
In the hypothalamic paraventricular nucleus (PVN), the proenkephalin gene may be upregulated by lipopolysaccharide (LPS) and downregulated by the GABA-A agonist muscimol. Candidate transcription factors regulating the proenkephalin gene in opposite directions are cAMP-response-element-binding protein (CREB) (when phosphorylated, a positive regulator) and cAMP-responsive modulatory inducible cAMP early repressor (CREM/ICER) (a negative regulator). Our results demonstrate that CREM alpha,beta,gamma transcripts and ICER are induced in the PVN by LPS and remain elevated for periods of up to 12 h. PhosphoCREB is elevated after LPS administration, peaking at 8 h, but remaining elevated over control levels at 12 h. Phospho-CREB induction by LPS is also seen in primary hypothalamic cultures. Cotransfection of ICER with ENK-CAT12 into primary hypothalamic cultures produced a decrease in chloramphenicol acetyl transferase (CAT) levels following cAMP or LPS stimulation. PhosphoCREB is downregulated and CREM/ICER is upregulated in the PVN by muscimol, suggesting that the regulation of these transcription factors may underlie the inhibitory effect of muscimol on target genes in the PVN.
1-Methyl-3-isobutylxanthine↗