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Biomedical subjects

S Wright

Publications and source records attributed to S Wright.

At least 55 records · Page 3Linked to original sources
PubMed2001

Immunity to experimental neosporosis in pregnant sheep.

Neospora caninum is an important cause of fetal loss in cattle but has also infrequently been shown to cause disease in sheep and goats. Experimental infection of pregnant sheep with N. caninum causes clinical and pathological changes very similar to those of neosporosis in cattle. An experiment in sheep was undertaken to examine whether infection with N. caninum before pregnancy conferred immunity to subsequent challenge with the parasite during pregnancy. Primary inoculation of NC1 tachyzoites subcutaneously, either before or during pregnancy, caused a significant temperature response in ewes, while those given a secondary challenge at 90 days gestation (dg) did not show such a response. Primary infection of 12 ewes during pregnancy resulted in the loss of all fetuses while a further 12 ewes inoculated with NC1 tachyzoites before mating and subsequently challenged with the same dose at 90 dg produced nine live and seven dead lambs. There were no fetal deaths in ewes only infected with Neospora before mating although there was serological evidence of vertical transmission in four of their clinically normal offspring while Neospora DNA was detected in the cerebrospinal fluid of a fifth healthy lamb. Thus an experimental primary infection with N. caninum during pregnancy killed all the fetuses while inoculation before pregnancy did not cause any mortality but did provide a degree of protection against subsequent challenge with Neospora during pregnancy.

Animals↗
PubMed2001

Changes in management of diabetic retinopathy by Australian ophthalmologists as a result of the NHMRC clinical guidelines.

PURPOSE: To document changes in management of diabetic retinopathy by Australian ophthalmologists after release of the National Health and Medical Research Council (NHMRC) clinical guidelines. METHODS: Self-administered questionnaires were mailed to Australian ophthalmologists prior to release of the NHMRC guidelines for the management of diabetic retinopathy, and at one and 2.5 years after release of the guidelines. The questionnaires elicited information about current management practices in relation to diabetic retinopathy RESULTS: The response rate for the baseline and two follow-up surveys was 82%, 81%, and 80%, respectively. More than 85% of the ophthalmologists responded that the guidelines were useful in improving management, were easy to understand, and were already part of their routine clinical practice. A relatively small percentage (12%) felt that the guidelines made recommendations that were not practical or feasible. Contrary to the NHMRC guidelines, at the second follow-up survey, only 50% of the ophthalmologists said that they would almost never perform fluorescein angiography in eyes with mild non-proliferative diabetic retinopathy. The change from baseline to the second follow-up in the percentage of ophthalmologists who would perform cataract surgery after treating clinically significant macular oedema (as advised by the NHMRC guidelines) was statistically significant (baseline = 83.7%, 95% confidence limit = 80.4, 87.0; second follow up = 90.4, 95% confidence limit = 87.3, 93.5). CONCLUSIONS: Distribution of the printed NHMRC Clinical Practice Guidelines: Management of Diabetic Retinopathy and full colour Retinopathy Chart resulted in a significant change in the recommended order of treatment of clinically significant macular oedema. However no significant change in the use of fluorescein angiography was documented.

Australia↗
PubMed2001

Cholesterol ester accumulation: an immediate consequence of acute in vivo ischemic renal injury.

BACKGROUND: Cholesterol is a major constituent of plasma membranes, and recent evidence indicates that it is up-regulated during the maintenance phase of acute renal failure (ARF). However, cholesterol's fate and that of the cholesterol ester (CE) cycle [shuttling between free cholesterol (FC) and CEs] during the induction phase of ARF have not been well defined. The present studies sought to provide initial insights into these issues. METHODS: FC and CE were measured in mouse renal cortex after in vivo ischemia (15 and 45 minutes)/reperfusion (0 to 120 minutes) and glycerol-induced myoglobinuria (1 to 2 hours). FC/CE were also measured in (1) cultured human proximal tubule (HK-2) cells three hours after ATP depletion and in (2) isolated mouse proximal tubule segments (PTSs) subjected to plasma membrane damage (with cholesterol oxidase, sphingomyelinase, phospholipase A2, or cytoskeletal disruption with cytochalasin B). The impact of cholesterol synthesis inhibition (with mevastatin) and FC traffic blockade (with progesterone) on injury-evoked FC/CE changes was also assessed. RESULTS: In vivo ischemia caused approximately threefold to fourfold CE elevations, but not FC elevations, that persisted for at least two hours of reperfusion. Conversely, myoglobinuria had no effect. Isolated CE increments were observed in ATP-depleted HK-2 cells. Neither mevastatin nor progesterone blocked this CE accumulation. Plasma membrane injury induced with sphingomyelinase or cholesterol oxidase, but not with phospholipase A(2) or cytochalasin B, increased tubule CE content. High CE levels, induced with cholesterol oxidase, partially blocked hypoxic PTS attack. CONCLUSIONS: In vivo ischemia/reperfusion acutely increases renal cortical CE, but not FC, content, indicating perturbed CE/FC cycling. The available data suggest that this could stem from specific types of plasma membrane damage, which then increase FC flux via aberrant pathways to the endoplasmic reticulum, where CE formation occurs. That CE levels are known to inversely correlate with both renal and nonrenal cell injury suggests the potential relevance of these observations to the induction phase of ischemic ARF.

Acute Disease↗
PubMed2001

Ethylene glycol-mediated tubular injury: identification of critical metabolites and injury pathways.

Ethylene glycol (EG) intoxication produces multisystem organ injury, including acute renal failure. Although EG must be metabolized to toxic intermediates to induce organ damage, the specific metabolite(s) responsible and the underlying pathogenic mechanisms remain poorly defined. To explore these issues, isolated mouse proximal tubular segments (PTSs) were incubated with either varying doses of EG or its prime metabolites (glycolate, glycoaldehyde, glyoxylate, or oxalate for 15 to 60 minutes). Injury was assessed by the percentage of lactate dehydrogenase (LDH) release, LDH destruction, adenosine triphosphate (ATP) depletion, or membrane phospholipid degradation. Toxicities were also assessed in cultured HK-2 cells over 18 hours (by MTT assay). EG, glycolate, and oxalate did not induce overt PTS injury. Conversely, glyoxylate and glycoaldehyde were highly toxic, causing profound ATP depletion and LDH release. Glycoaldehyde also caused enzyme (LDH) and selected phospholipid degradation (phosphatidylethanolamine, phosphatidylserine). These changes were not seen with glyoxylate treatment. Acidosis (pH 6.8) and glycine (2 mmol/L) each blocked glyoxylate, but not glycoaldehyde toxicity, indicating differing injury pathways. Only glycoaldehyde and glyoxylate induced marked HK-2 cell death. We conclude that glycoaldehyde and glyoxylate are the principal metabolites responsible for EG nephrotoxicity and do so by causing ATP depletion and phospholipid and enzyme destruction. Glycine and acidosis, by-products of EG metabolism, can attenuate glyoxylate-mediated injury. This suggests that naturally occurring but incomplete protective pathways may be operative during the evolution of EG cytotoxicity.

Adenosine Triphosphate↗
PubMed2001

A novel condom policy for young attenders at a sexual health clinic.

OBJECTIVES: To review the uptake of a new service for condom provision in the under 16s. METHODS: A retrospective case note review of attenders at an inner London sexual health clinic. RESULTS: The service was audited over a 3 month period in the spring of 2000. There were 97 individual attendances, 94% (92) male and 6% (5) female. 89% (87) had never attended a sexual health service before. When asked how they had heard of the clinic 88% (86) said a friend had told them about the clinic. 66% (64) claimed not to be sexually active. CONCLUSIONS: A novel policy of condom distribution to groups of boys has been successfully piloted at an inner London sexual health clinic. This policy appears to be overcoming the reluctance of teenage boys to access sexual health services.

Adolescent↗
PubMed2001

The application of ground force explains the energetic cost of running backward and forward.

We compared backward with forward running to test the idea that the application of ground force to support the weight of the body determines the energetic cost of running. We hypothesized that higher metabolic rates during backward versus forward running would be directly related to greater rates of ground force application and the volume of muscle activated to apply support forces to the ground. Four trained males ran backward and forward under steady-state conditions at eight treadmill speeds from 1.75 to 3.50 m x s(-1). Rates of oxygen uptake were measured to determine metabolic rates, and inverse periods of foot-ground contact (1/tc) were measured to estimate rates of ground force application. As expected, at all eight speeds, both metabolic rates and estimated rates of ground force application were greater for backward than for forward running. At the five slowest speeds, the differences in rates of ground force application were directly proportional to the differences in metabolic rates between modes (paired t-test, P<0.05), but at the three highest speeds, small but significant differences in proportionality were present in this relationship. At one of these three higher speeds (3.0 m x s(-1)), additional measurements to estimate muscle volumes were made using a non-invasive force plate/video technique. These measurements indicated that the volume of muscle active per unit of force applied to the ground was 10+/-3% greater when running backward than forward at this speed. The product of rates of ground force application and estimated muscle volumes predicted a difference in metabolic rate that was indistinguishable from the difference we measured (34+/-6% versus 35+/-6%; means +/- s.e.m., N=4). We conclude that metabolic rates during running are determined by rates of ground force application and the volume of muscle activated to apply support forces to the ground.

Adult↗
PubMed2001

Comparison of neonicotinoid insecticides for use with biodegradable and wooden spheres for control of key Rhagoletis species (Diptera: Tephritidae).

Field-based studies and laboratory bioassays were conducted with apple maggot, Rhagoletis pomonella (Walsh), and blueberry maggot, Rhgoletis mendax Curran, flies to investigate the performance and duration of activity of insecticide-treated biodegradable and wooden spheres for control of Rhagoletis species. Four neonicotinoid insecticide treatments including imidacloprid, thiamethoxam, and thiocloprid at 2% (AI) were evaluated with biodegradable spheres. In 1999, significantly more apple maggot flies were found killed by imidacloprid-treated spheres compared with thiamethoxam-treated spheres during early and late season. In 2000, spheres treated with either of two formulations of imidacloprid killed significantly more apple maggot flies compared with thiamethoxam, thiocloprid, and untreated spheres. In blueberries, there were no significant differences between the numbers of blueberry maggot flies killed by both imidacloprid-treated or thiamethoxam-treated spheres in 1999. However, during the 2000 blueberry field season, both formulations of imidacloprid were significantly more effective in killing blueberry maggot flies compared with spheres treated with thiamethoxam, thiocloprid and untreated controls. Overall, spheres treated with thiocloprid were ineffective and did not kill significantly more apple maggot or blueberry maggot flies compared with the controls. Laboratory bioassays showed that the effectiveness of field-exposed spheres treated with imidacloprid at 4 and d 8% (AI) and thiamethoxam at 4% (AI) in killing apple maggot flies was not significantly reduced over a 12-wk aging period. Additionally, wooden spheres aged outdoors for 12 wk with and without mold maintained residual activity in laboratory tests, whereas biodegradable spheres of equal aging, with and without mold lost their effectiveness in killing apple maggot flies. In other studies, we confirmed that the addition of an external feeding stimulant (sucrose) significantly increases the effectiveness of both biodegradable and wooden spheres treated with imidacloprid at 2% (AI).

Animals↗
PubMed2001

Ovulation rate and litter size in gilts immunized against androstenedione and 17alpha-hydroxyprogesterone.

Two experiments were conducted to evaluate the effects of the immunization of gilts against ovarian steroids on ovulation rate and litter size. In Exp. 1, gilts (n = five gilts/treatment) at 165+/-1.6 d of age were immunized against either carrier (Control), androstenedione, or 17alpha-hydroxyprogesterone. Age at puberty and estrous cycle length averaged 208+/-5.5 (P = 0.67) and 20.3+/-2.8 d (P = 0.41), respectively, and were not affected by treatment. The androstenedione- and 17alpha-hydroxyprogesterone immunized gilts had higher (P < 0.02) ovulation rates than Controls (14.2, 14.2, and 11.4+/-0.8, respectively). Total pigs born (P = 0.66) and pigs born live (P = 0.65) for the androstenedione-treated group were not different from Controls. Gestation length was not different (P = 0.36) between any of the treatments and the Controls (115+/-0.9 d). Procedures used in Exp. 2 were similar to those in Exp. 1, except that only Control (n= 18) and 17alpha-hydroxyprogesterone (n = 16) treatments were included and only litter size at farrowing was measured. Total pigs and pigs born live were higher in the 17a-hydroxyprogesterone-treated gilts than in the Controls (12.6 vs 10.5+/-0.6, P < 0.02; and 11.4 vs 9.2+/-0.6; P < 0.01, respectively). Data from this study indicate that litter size in gilts can be increased by immunization against 17alpha-hydroxyprogesterone.

17-alpha-Hydroxyprogesterone↗
PubMed2001

DNA and cell cycle analysis as prognostic indicators in breast tumors revisited.

Both DNA ploidy and S-phase ploidy are promising prognostic factors for node-negative breast cancer patients. Based largely on the analysis of one large study, much of the reported problems with these factors have been caused by some unappreciated complexities in categorizing DNA ploidy into low- and high-risk groups and the lack of some necessary adjustments to eliminate unwanted correlations between DNA S-phase and ploidy. When both DNA ploidy and S-phase are compensated properly, they become independent prognostic markers, forming a powerful prognostic model.

Breast Neoplasms↗
PubMed2000

Linkage analysis for major histocompatibility complex-related genetic susceptibility in familial chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) shows evidence of familial aggregation, but the genetic basis is poorly understood. The existence of a linkage between HLA and Hodgkin lymphoma, another B-cell disorder, coupled with the fact that CLL is frequently associated with autoimmune disease, led to the question of whether the major histocompatibility complex (MHC) region is involved in familial cases of CLL. To examine this proposition, 5 microsatellite markers on chromosome 6p21.3 were typed in 28 families with CLL, 4 families with CLL in association with other lymphoproliferative disorders, and 1 family with splenic lymphoma with villous lymphocytes. There was no evidence of linkage in these families to chromosome 6p21.3. The best estimates of the proportions of sibling pairs with CLL that share 0, 1, or 2 MHC haplotypes were not significantly different from the null expectation. This implies that genes within the MHC region are unlikely to be the major determinants of familial CLL. (Blood. 2000;96:3982-3984)

Adult↗
PubMed2000

Pilot study of high-frequency ultrasound to assess cutaneous oedema in the conservatively managed breast.

Cutaneous oedema is a relatively frequent complication in patients treated conservatively for breast cancer. The factors that contribute to this complication have not been precisely determined. We performed a pilot study to assess the usefulness of high-frequency ultrasound as a quantitative measure of cutaneous oedema. Eleven patients undergoing breast-conserving therapy for breast cancer were studied. Both the treated and untreated breasts were examined. Total cutaneous thickness provided a useful measure of cutaneous oedema. The treated breast was significantly thicker than the untreated breast (P < 0.001). The medial aspect of the breast was thicker than the lateral aspect in both the treated and untreated breast (P < 0.001). The increase in cutaneous thickness predated radiotherapy in those patients who had undergone an axillary dissection. Intrapatient variation in skin thickness was much less than interpatient variation in skin thickness (coefficient of variation 6.4% vs. 18.2% for the untreated breast; coefficient of variation 13.9% vs. 30.9% for the treated breast). Increasing cutaneous thickness was associated with decreasing cutaneous echodensity. We were unable to derive quantitative estimates of echodensity. Cutaneous oedema is an important outcome variable following conservative treatment of breast cancer. High-frequency ultrasound is able to quantify this accurately. It can readily detect changes invisible to the naked eye. High-frequency ultrasound should enable the effects of different treatment options (e.g., extent of surgery, radiotherapy, and chemotherapy) on cutaneous oedema to be differentiated and for the time course of oedema to be accurately characterised.

Aged↗
PubMed2000

Ocean circulation off east Antarctica affects ecosystem structure and sea-ice extent.

Sea ice and oceanic boundaries have a dominant effect in structuring Antarctic marine ecosystems. Satellite imagery and historical data have identified the southern boundary of the Antarctic Circumpolar Current as a site of enhanced biological productivity. Meso-scale surveys off the Antarctic peninsula have related the abundances of Antarctic krill (Euphausia superba) and salps (Salpa thompsoni) to inter-annual variations in sea-ice extent. Here we have examined the ecosystem structure and oceanography spanning 3,500 km of the east Antarctic coastline, linking the scales of local surveys and global observations. Between 80 degrees and 150 degrees E there is a threefold variation in the extent of annual sea-ice cover, enabling us to examine the regional effects of sea ice and ocean circulation on biological productivity. Phytoplankton, primary productivity, Antarctic krill, whales and seabirds were concentrated where winter sea-ice extent is maximal, whereas salps were located where the sea-ice extent is minimal. We found enhanced biological activity south of the southern boundary of the Antarctic Circumpolar Current rather than in association with it. We propose that along this coastline ocean circulation determines both the sea-ice conditions and the level of biological productivity at all trophic levels.

Animals↗
PubMed2000

Transposon diversity in Arabidopsis thaliana.

Recent availability of extensive genome sequence information offers new opportunities to analyze genome organization, including transposon diversity and accumulation, at a level of resolution that was previously unattainable. In this report, we used sequence similarity search and analysis protocols to perform a fine-scale analysis of a large sample ( approximately 17.2 Mb) of the Arabidopsis thaliana (Columbia) genome for transposons. Consistent with previous studies, we report that the A. thaliana genome harbors diverse representatives of most known superfamilies of transposons. However, our survey reveals a higher density of transposons of which over one-fourth could be classified into a single novel transposon family designated as Basho, which appears unrelated to any previously known superfamily. We have also identified putative transposase-coding ORFs for miniature inverted-repeat transposable elements (MITEs), providing clues into the mechanism of mobility and origins of the most abundant transposons associated with plant genes. In addition, we provide evidence that most mined transposons have a clear distribution preference for A + T-rich sequences and show that structural variation for many mined transposons is partly due to interelement recombination. Taken together, these findings further underscore the complexity of transposons within the compact genome of A. thaliana.

Amino Acid Sequence↗
PubMed2000

The plasmin system is induced by and degrades amyloid-beta aggregates.

Amyloid-beta (Abeta) appears critical to Alzheimer's disease. To clarify possible mechanisms of Abeta action, we have quantified Abeta-induced gene expression in vitro by using Abeta-treated primary cortical neuronal cultures and in vivo by using mice transgenic for the Abeta precursor (AbetaP). Here, we report that aggregated, but not nonaggregated, Abeta increases the level of the mRNAs encoding tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Moreover, tPA and uPA were also upregulated in aged AbetaP overexpressing mice. Because others have reported that Abeta aggregates can substitute for fibrin aggregates in activating tPA post-translationally, the result of tPA induction by Abeta would be cleavage of plasminogen to the active protease plasmin. To gain insights into the possible actions of plasmin, we evaluated the hypotheses that tPA and plasmin may mediate Abeta in vitro toxicity or, alternatively, that plasmin activation may lead to Abeta degradation. In evaluating these conflicting hypotheses, we found that purified plasmin degrades Abeta with physiologically relevant efficiency, i.e., approximately 1/10th the rate of plasmin on fibrin. Mass spectral analyses show that plasmin cleaves Abeta at multiple sites. Electron microscopy confirms indirect assays suggesting that plasmin degrades Abeta fibrils. Moreover, exogenously added plasmin blocks Abeta neurotoxicity. In summation, we interpret these results as consistent with the possibility that the plasmin pathway is induced by aggregated Abeta, which can lead to Abeta degradation and inhibition of Abeta actions.

Amino Acid Sequence↗
PubMed2000

Continuity of care and clinical outcome: a prospective cohort study.

BACKGROUND: Continuity of care is a central objective of community psychiatric services, but there is no consensus about its measurement. AIMS: We developed measures of continuity of care suitable for routine use, and measured continuity and individual patient outcome over a period in which community services were developing. METHOD: One hundred patients with severe mental illness receiving continuing care from two sectorised services were sampled and interviewed. Data were collected concerning their care over 20 months prior to interview. After 20 months prospective follow-up, they were re-interviewed. Continuity was defined as: perceived accessibility of services and knowledge about them, the number of keyworkers in a defined period of time, and the proportion of time out of contact with services. RESULTS: Continuity of care improved significantly on all measures over the period of the study. Individual patient outcome also improved, but in multiple regression models including clinical and demographic variables, measures of continuity were not significant predictors of outcome. Continuity was similar for white and non-white patients. CONCLUSION: Simple measures of continuity are useful in evaluating changes in the process of care, but they are not straightforwardly related to individual outcome.

Adult↗
PubMed2000

Dual diagnosis in the suburbs: prevalence, need, and in-patient service use.

BACKGROUND: Previous research has found comorbid severe mental illness and substance misuse (dual diagnosis) to be highly prevalent and to be associated with serious clinical and social problems, and increased service use in inner-city populations. The present study measures the prevalence of dual diagnosis, patterns of substance misuse, and associated in-patient use in a more demographically representative population in a suburban area of South London. METHOD: We identified representative prevalent cases with psychotic illnesses who had been in contact with services in a geographically defined catchment area in Croydon over the previous 6 months. Cases of alcohol or substance misuse and dependence were identified through standardised interviews with patients and keyworkers, and sociodemographic and in-patient psychiatric service use data were also recorded. RESULTS: Sixty-one of the 124 cases identified were randomly selected for interview, of whom 66% responded (N = 40). The prevalence rates of dual diagnosis (DD) observed were 33% (95% CI 18-47%) for any substance misuse, 20% (95% CI 8-32%) for alcohol misuse only, 5% (95% CI-16 to 26%) for drug misuse only, and 8% (95% CI -0.7 to 16%) for both drug and alcohol misuse. A lifetime history of any illicit drug use was observed in 35% of the sample (95% CI 20-50%). Patients who misuse alcohol and drugs were not found to be more likely to have been admitted to hospital in the previous 2 years, with little difference being observed between DD and psychosis-only patients in the mean number of in-patient admissions in this period (mean difference 0.25, 95% CI for difference -1.5 to 2.0). However, the DD patients were found to have spent on average over twice as long in hospital as other psychotic in-patients over the previous 2 years (mean difference 67.3 days, 95% CI for difference -205.9 to 71.2 days). DD patients were also found to have a greater number of unmet areas of need than the psychosis-only patients, which included accommodation, daytime activity, and social life, as well as substance misuse. CONCLUSIONS: The prevalence of substance misuse in patients with severe mental disorders in a suburban area is about as high as that for similar patients in inner-city London. While DD patients are not admitted more often than patients with psychosis alone, they have double the length of in-patient stay, which may be attributable to higher levels of unmet need.

Catchment Area, Health↗