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Biomedical subjects

K Thompson

Publications and source records attributed to K Thompson.

At least 19 recordsLinked to original sources
PubMed2007

Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study.

OBJECTIVE: To describe the prevalence, characteristics, attribution, and clinical significance of neuropsychiatric (NP) events in an international inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: The study was conducted by the Systemic Lupus International Collaborating Clinics (SLICC). Patients were enrolled within 15 months of fulfilling the American College of Rheumatology (ACR) SLE classification criteria. All NP events within a predefined enrollment window were identified using the ACR case definitions of 19 NP syndromes. Decision rules were derived to determine the proportion of NP disease attributable to SLE. Clinical significance was determined using the Short Form 36 (SF-36) Health Survey and the SLICC/ACR Damage Index (SDI). RESULTS: A total of 572 patients (88% female) were recruited, with a mean +/- SD age of 35 +/- 14 years. The mean +/- SD disease duration was 5.2 +/- 4.2 months. Within the enrollment window, 158 of 572 patients (28%) had at least 1 NP event. In total, there were 242 NP events that encompassed 15 of 19 NP syndromes. The proportion of NP events attributed to SLE varied from 19% to 38% using alternate attribution models and occurred in 6.1-11.7% of patients. Those with NP events, regardless of attribution, had lower scores on the SF-36 and higher SDI scores compared with patients with no NP events. CONCLUSION: Twenty-eight percent of SLE patients experienced at least 1 NP event around the time of diagnosis of SLE, of which only a minority were attributed to SLE. Regardless of attribution, the occurrence of NP events was associated with reduced quality of life and increased organ damage.

Adult↗
PubMed2006

Microdissection-based high-resolution genomic array analysis of two patients with cytogenetically identical interstitial deletions of chromosome 1q but distinct clinical phenotypes.

We describe two boys with cytogenetically identical interstitial deletions in the q42.11-q42.13 region of the long arm of chromosome 1 detected by high-resolution G-banding analysis. These children share some phenotypic features but also exhibit distinct morphologic differences. We further characterized the deletions using a new technical strategy--microdissection-based high-resolution genomic array (MHGA) analysis--to define the breakpoints, genomic sizes, and gene contents of the deletions. This showed that the patients had distinguishable deletions that were adjacent but did not overlap, thus explaining the observed phenotypic differences. These results were surprising because we expected at least some degree of overlap to explain the features that were shared. MHGA can quickly give precise and detailed information about any rearrangement in the genome using as little material as a single cell. This novel strategy provides unique advantages for both clinical diagnosis and genomic research.

Child, Preschool↗
PubMed2006

In situ site-specific specimen preparation for atom probe tomography.

Techniques for the rapid preparation of atom-probe samples extracted directly from a Si wafer are presented and discussed. A systematic mounting process to a standardized microtip array allows approximately 12 samples to be extracted from a near-surface region and mounted for subsequent focused-ion-beam sharpening in a short period of time, about 2h. In addition, site-specific annular mill extraction techniques are demonstrated that allow specific devices or structures to be removed from a Si wafer and analyzed in the atom-probe. The challenges presented by Ga-induced implantation and damage, particularly at a standard ion-beam accelerating voltage of 30 keV, are shown and discussed. A significant reduction in the extent of the damaged regions through the application of a low-energy "clean-up" ion beam is confirmed by atom-probe analysis of the damaged regions. The Ga+ penetration depth into {100} Si at 30 keV is approximately 40 nm. Clean-up with either a 5 or 2 keV beam reduces the depth of damaged Si to approximately 5 nm and <1 nm, respectively. Finally, a NiSi sample was extracted from a Si wafer, mounted to a microtip array, sharpened, cleaned up with a 5 keV beam and analyzed in the atom probe. The current results demonstrate that specific regions of interest can be accessed and preserved throughout the sample-preparation process and that this preparation method leads to high-quality atom probe analysis of such nano-structures.

Journal Article↗
PubMed2006

Pre-transplant ganciclovir and post transplant high-dose valacyclovir reduce CMV infections after alemtuzumab-based conditioning.

Alemtuzumab (Campath-1H)-based conditioning regimens are effective in preventing GVHD, but are associated with very high rates of cytomegalovirus (CMV) infection, a major limitation to their use. We evaluated 85 patients receiving conditioning with fludarabine 30 mg/m2/day (day -7 to day -3), alemtuzumab 20 mg/day (day -7 to day -3), and melphalan 140 mg/m2 on day -2. The initial patients received post transplant CMV prophylaxis with high-dose acyclovir. A very high incidence of CMV viremia was observed as has been commonly reported after alemtuzumab-based conditioning. Sixty-seven subsequent patients received pre-transplant ganciclovir and high-dose valacyclovir after engraftment. The cumulative incidence of CMV infection in the valacyclovir cohort was 29%. This compared favorably to the cumulative incidence of 53% in patients receiving only acyclovir (P = 0.004) and to literature data. CMV prophylaxis with pre-transplant ganciclovir and high-dose valacyclovir after engraftment appears effective in preventing the excessive incidence of CMV infection after alemtuzumab-based conditioning regimens.

Acyclovir↗
PubMed2006

Does a first trimester dating scan using crown rump length measurement reduce the rate of induction of labour for prolonged pregnancy? An uncompleted randomised controlled trial of 463 women.

OBJECTIVE: To evaluate the effect of a first trimester ultrasound dating scan on the rate of induction of labour for prolonged pregnancy. DESIGN: Randomised controlled trial to include 400 women in each arm of the trial. SETTING: Participating general practices and a district general teaching hospital. POPULATION: Women attending their general practitioner in the first trimester to confirm pregnancy, in whom a first trimester ultrasound scan was not indicated. METHODS: Women randomised to the study group (scan group) underwent an ultrasound dating scan between 8 and 12 weeks, measuring crown-rump length. The estimated date of delivery (EDD) was changed if there was a discrepancy of more than 5 days from the gestation, calculated from the last menstrual period (LMP). For the remaining women (no-scan group), gestation was determined using the LMP. MAIN OUTCOME MEASURES: The rate of induction of labour for prolonged pregnancy. RESULTS: Due to circumstances beyond the researchers' control, recruitment was abandoned when 463 women had been enrolled. The EDD was adjusted in 13 (5.7%) women in the scan group and in 2 (0.9%) in the no-scan group. There was no difference in the rate of induction for prolonged pregnancy between the scan (19 [8.2%]) and the no-scan (17 [7.4%]) groups (relative risk 1.10; 95% CI 0.59-2.07). CONCLUSIONS: Acknowledging the reduced numbers recruited for study, it is concluded that there is no evidence that a first trimester ultrasound dating scan reduces the rate of induction of labour for prolonged pregnancy and may result in a more expensive healthcare strategy.

Adult↗
PubMed2006

Compliance with routine antenatal rhesus D prophylaxis and the impact on sensitisations: observations over 14 years.

Documented routine antenatal anti-D prophylaxis was given to 90% and 81-87% of eligible women at 28 and 34 weeks of gestation, respectively, during the early 1990s and early 2000s. With increasing experience and education, a significant improvement in the timing of the first (OR 0.26, 95% CI 0.16-0.41: P < 0.0001) and second injections (OR 0.40, 95% CI 0.26-0.61: P < 0.0001) occurred during the latter period. Despite these improvements, there was no reduction in the sensitisation rate at 0.4%. However, this low rate occurred despite significant proportions of women delivering more than 42 days after the second injection. Fifteen of the 16 sensitised women had received routine antenatal prophylaxis.

Female↗
PubMed2006

Clonidine in horses: identification, detection, and clinical pharmacology.

Clonidine is classified as a class 3 performance-enhancing agent by the Association of Racing Commissioners International and thus has the potential to influence the outcome of a race. In this study, the authors developed and validated a sensitive gas chromatograph and mass spectrometer method to determine the pharmacokinetic parameters of clonidine in equine plasma samples after IV administration of a single dose (0.025 mg/kg) of clonidine in horses. At this dose, clonidine produced rapid and profound sedation, which cold be quickly reversed with yohimbine. Clonidine was able to produce an analgesic effect but failed to provide maximal analgesia in all horses; the limited analgesic effect persisted for about 60 minutes.

Adrenergic alpha-Agonists↗
PubMed2005

Biodiversity in urban habitat patches.

We examined the biodiversity of urban habitats in Birmingham (England) using a combination of field surveys of plants and carabid beetles, genetic studies of four species of butterflies, modelling the anthropochorous nature of the floral communities and spatially explicit modelling of selected mammal species. The aim of the project was to: (i) understand the ecological characteristics of the biota of cities model, (ii) examine the effects of habitat fragment size and connectivity upon the ecological diversity and individual species distributions, (iii) predict biodiversity in cities, and (iv) analyse the extent to which the flora and fauna utilise the 'urban greenways' both as wildlife corridors and as habitats in their own right. The results suggest that cities provide habitats for rich and diverse range of plants and animals, which occur sometimes in unlikely recombinant communities. The studies on carabids and butterflies illustrated the relative importance of habitat quality on individual sites as opposed to site location within the conurbation. This suggests that dispersal for most of our urban species is not a limiting factor in population persistence, although elements of the woodland carabid fauna did appear to have some geographical structuring. Theoretical models suggested that dormice and water voles may depend on linear habitats for dispersal. The models also indicated that other groups, such as small and medium sized mammals, may use corridors, although field-based research did not provide any evidence to suggest that plants or invertebrates use urban greenways for dispersal. This finding indicates the importance of identifying a target species or group of species for urban greenways intended as dispersal routeways rather than as habitat in their own right. Their importance for most groups is rather that greenways provide a chain of different habitats permeating the urban environment. We suggest that planners can have a positive impact on urban biodiversity by slowing the pace of redevelopment and by not hurrying to tidy up and redevelop brownfield sites.

Animals↗
PubMed2005

Visual impairment in elderly patients with hip fracture: causes and associations.

AIMS: To evaluate the current visual status and ophthalmic history of a sample of elderly patients with fractured neck of femur and to study the relationship between visual status and demographic factors. METHODS: A four-centre study of all patients admitted to hospital with fractured neck of femur. The setting was two district (Ayr, Dunfermline) and two teaching (Glasgow, Dundee) hospitals in Scotland. The study examined 537 patients aged 65 years and over admitted with acute fractured neck of femur to hospital. RESULTS: Bilateral visual impairment (binocular visual acuity worse than 6/12) was found in 239 of 518 patients (46%). Of this group, the principal causes for visual deficit were untreated cataract (49%), macular degeneration (21%), uncorrected refractive error (17%), and glaucoma (3%). The visually impaired group were more likely to have symptomatic visual complaints (58 vs 26%), however, were less likely to be under optometric care (71 vs 85%). A higher proportion of the group with visual impairment lived in areas of social deprivation (40 vs 26%). CONCLUSIONS: Patients with fractured neck of femur represent a frail elderly group that have poorer vision than that documented in any other elderly population. The visual defect was potentially remediable in the majority of cases but this group of individuals are not generally in touch with the ophthalmic services. Social deprivation appears to be associated with this groups' inability to access ophthalmic care.

Aged↗
PubMed2005

Optometric and ophthalmic contact in elderly hip fracture patients with visual impairment.

AIM: To describe previous contact with optometry and ophthalmic services in a group of elderly patients with and without visual impairment (VI) who had fallen and sustained a fractured neck of femur. METHOD: A cross sectional study of 537 patients aged 65 and over who had undergone hip fracture surgery in four Scottish centres (Glasgow, Ayr, Dundee and Fife). All patients had an in-depth optometric history, ophthalmic history and examination. RESULTS: Three hundred and ninety-three (79%) patients reported optometric contact in the 3 years preceding surgery and 107 (21%) patients had not seen an optometrist for more than 3 years. In the latter group, 64 had VI, which was due to uncorrected refractive error in 17 (27%) and untreated cataract in 20 (31%). VI (best binocular visual acuity of 6/18 or less) was found in 239 (46%) patients. A past ophthalmic history was present in 257 (50%) patients. Only 39 (16%) patients with VI were under ophthalmic care at the time of the study. CONCLUSIONS: There was significantly poor optometric and ophthalmic contact in patients who had VI and had fallen and sustained hip fracture. A proportion of the VI (66%) was due to uncorrected refractive error and untreated cataract. Public health providers should be made aware of the fact that current optometric and ophthalmic care pathways are not accessed by this group of elderly patients with VI and at risk of falling.

Accidental Falls↗
PubMed2004

Effect of manipulation of iron storage, transport, or availability on myelin composition and brain iron content in three different animal models.

Several observations suggest that iron is an essential factor in myelination and oligodendrocyte biology. However, the specific role of iron in these processes remains to be elucidated. This role could be as an essential cofactor in metabolic processes or as a transcriptional or translational regulator. In this study, we used animals models each with a unique defect in iron availability, storage, or transfer to test the hypothesis that disruptions in these mechanisms affect myelinogenesis and myelin composition. Disruption of iron availability either by limiting dietary iron or by altering iron storage capacity resulted in a decrease in myelin proteins and lipids but not the iron content of myelin. Among the integral myelin proteins, proteolipid protein was most consistently affected, suggesting that limiting iron to oligodendrocytes results not only in hypomyelination but also in a decrease in myelin compaction. Mice deficient in transferrin must receive transferrin injections beginning at birth to remain viable, and these mice had increases in all of the myelin components and in the iron content of the myelin. This finding indicates that the loss of endogenous iron mobility in oligodendrocytes could be overcome by application of exogenous transferrin. Overall, the results of this study demonstrate how myelin composition can be affected by loss of iron homeostasis and reveal specific chronic changes in myelin composition that may affect behavior and attempts to rescue myelin deficits.

Animals↗
PubMed2004

Desloratadine partially inhibits the augmented bacterial responses in the sinuses of allergic and infected mice.

BACKGROUND: Allergic rhinitis (AR) is considered a major predisposing factor for the development of acute bacterial rhinosinusitis. How AR augments a bacterial infection is unknown. OBJECTIVE: Our purpose in this study was to test whether an H1 receptor antagonist, desloratadine, could reduce the augmented effect of an ongoing allergic reaction on acute bacterial rhinosinusitis. METHODS: Three groups of infected and ovalbumin (OVA)-sensitized mice were studied: (1) infected and allergic mice treated with desloratadine, (2) infected and allergic mice treated with placebo, and (3) infected mice. A fourth group of uninfected, non-sensitized mice served as a control for the cellular changes. BALB/c mice were sensitized by two intraperitoneal injections of OVA given 8 days apart. One day after the second injection, the mice were nasally exposed daily to 6% OVA (the groups treated with desloratadine or placebo) or phosphate-buffered saline (PBS) (the infection-only group) for 5 days. After the second OVA exposure, the mice were intranasally inoculated with Streptococcus pneumoniae. Desloratadine or placebo was given daily throughout the OVA exposure period. Nasal allergic symptoms were observed by counting of nasal rubbing and sneezing for 10 min after OVA or PBS nasal challenge. On day 5 post-infection, nasal lavage culture was done, and the inflammatory cells in the sinuses were evaluated by flow cytometry. RESULTS: Mice that were made allergic, infected, and treated with placebo showed more organisms and phagocytes than did only infect mice. They also manifested allergic nasal symptoms and eosinophil influx into the sinuses. Desloratadine treatment during allergen exposure reduced allergic symptoms and reduced sinonasal infection (P<0.05). There tended to be less myeloid cell and neutrophil influx (P=0.09 both), but not eosinophil influx (P=0.85) compared with that in the placebo-treated group. CONCLUSION: Desloratadine treatment during nasal challenge inhibited allergic symptoms and reduced sinonasal infection, suggesting that histamine via an H1 receptor plays a role in the augmented infection in mice with an ongoing allergic reaction.

Animals↗
PubMed2004

An assessment of mother-to-child HIV transmission prevention in 16 pilot antenatal clinics in Jamaica.

OBJECTIVES: This study aims to determine the number and age distribution of pregnant women testing positive for HIV at 16 selected clinics in Jamaica between 2001 and 2002; the utilization of therapeutic interventions to minimize the risk of mother-to-child transmission (MTCT) and the current status of the HIV-exposed infants and, finally, the number of children who received testing for detection of HIV and to calculate the incidence of MTCT in these children. METHODS: A retrospective study was carried out at sixteen pilot clinic sites by examining the patient records for all confirmed HIV-positive pregnant mothers and the resultant infants at these facilities for the period January 2001 to December 2002. RESULTS: One hundred and twenty-three of 8116 pregnant women newly tested positive during the period January 2001 to December 2002; however, 176 HIV+ women delivered. Fifty-three (30%) knew their HIV status prior to participating in the programme. Sixty-two (1.4%) and 61 (1.6%) tested positive in 2001 and 2002, respectively. One hundred and ten (77%) and 113 (83%) mothers and infants, respectively, received ARV therapy, (92% - nevirapine, 8% - zidovudine). Twenty-three per cent of pregnant women received no ARV Forty-four (25.0%) of the 176 infants had a documented ELISA HIV test before eighteen months of age, none had a PCR test. The health status of 40 (23%) of these children was known: 30 (75%) were alive and well, five of whom did not receive any ARV, one (2.5%) was alive and ill and nine (22.5%) were reported dead, five of whom received ARV; 28.6% of infants who did not receive ARV were reported as either dead or ill compared to 13.8% of those receiving ARV CONCLUSION: Though the majority of pregnant women discovered their HIV status during pregnancy, a significant number got pregnant knowing that they were HIV+. The majority of mothers and infants received ARV but the follow-up and testing of infants was limited. Nevirapine is clearly protective in the prevention of MTCT of HIV and should be made universally accessible. All infants delivered to HIV+ mothers should be identified and tested for HIV.

AIDS Serodiagnosis↗
PubMed2003

Low molecular weight heparin for the prevention of hepatic veno-occlusive disease (VOD) after hematopoietic stem cell transplantation: a prospective phase II study.

We evaluated 40 patients undergoing high-dose chemo/radiotherapy (HDCT) and hematopoietic stem cell transplantation (HSCT) (allogeneic (22), autologous (18)) to determine the safety and feasibility of administering low molecular weight heparin (LMWH) as hepatic veno-occlusive disease (VOD) prophylaxis. Patients received a once daily subcutaneous injection of dalteparin 2500 anti-Xa i.u. commencing the day prior to starting HDCT, and continuing until day +30 post HSCT or hospital discharge, whichever came first. Dosage adjustments were made for patients developing renal failure. All bleeding episodes were recorded and graded and VOD was diagnosed and graded according to Seattle criteria. At 100 days of follow-up, the overall survival and probability of regimen-related mortality were 85 and 15%, respectively. Nine patients developed VOD. The probability of developing VOD post allogeneic and autologous HSCT was 28% (95% CI, 6-45) and 17% (95% CI, 0-32), respectively. VOD was graded as moderate (n=8) and severe (n=1). VOD resolved in all cases except for one patient who died secondary to severe VOD and multiorgan failure. Clinically significant bleeding episodes occurred in three patients; 24 patients developed minor bleeding not requiring specific therapy. All bleeding episodes resolved. These results suggest that LMWH for VOD prophylaxis is safe with a low incidence of serious bleeding events. Whether it is superior to unfractionated heparin, however, is unknown and should be addressed within the context of a randomized controlled trial.

Adolescent↗
PubMed2003

The usefulness of ultrasound assessment of amniotic fluid in predicting adverse outcome in prolonged pregnancy: a prospective blinded observational study.

OBJECTIVE: To determine whether a single ultrasound scan at or beyond 40 weeks of gestation to detect a single deepest pool of amniotic fluid <2 cm and amniotic fluid index (AFI) <5 cm is clinically useful in the prediction of subsequent adverse pregnancy outcome. DESIGN: A prospective double blind cohort study. SETTING: A university teaching hospital delivering approximately 6000 women annually. POPULATION: One thousand and five hundred and eighty-four pregnant women at or beyond 40 weeks of gestation. METHODS: Ultrasound assessment of liquor to detect the single deepest pool of amniotic fluid and derive the AFI at or after 40 weeks of gestation. MAIN OUTCOME MEASURES: Perinatal death, meconium aspiration, birth asphyxia, intervention in labour for fetal distress, a cord arterial pH <7 and admission to the neonatal unit. RESULTS: An AFI <5 cm but not a single deepest pool <2 cm was significantly associated with birth asphyxia or meconium aspiration. An AFI <5 cm was also significantly associated with caesarean section for fetal distress in labour, a cord arterial pH <7 at delivery and low Apgar scores. Despite there being a statistically significant association with adverse outcomes the sensitivity of AFI was low at 28.6%, 12% and 11.5% for major adverse outcome, fetal distress in labour or admission to the neonatal unit, respectively. CONCLUSIONS: The AFI is superior to a measure of the single deepest pool as an assessment of the fetus at or after 40 weeks but has a poor sensitivity for adverse pregnancy outcome. Routine use is likely to lead to increased obstetric intervention without improvement in perinatal outcomes.

Adult↗
PubMed2002

Allogeneic hematopoietic stem cell transplantation for progressive follicular lymphoma.

Between 1993 and 2000, 24 patients with follicular lymphoma underwent high-dose chemo/radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Median age was 44 years, median interval from diagnosis to HSCT was 24 months and the median number of prior lines of treatment was three. Donor source was HLA matched sibling (23) or matched unrelated donor (one). Conditioning therapy was busulfan based in 22 patients and included total body irradiation in two. All patients received i.v. cyclosporine A and short-course methotrexate for GVHD prophylaxis. Nineteen patients are alive, a median of 2.3 years post HSCT. Death occurred due to transplant complications in four patients and one patient died of a stroke 10 months post HSCT. No patients have relapsed. The overall and progression-free survival was 78% (95% CI 63-97). Allogeneic HSCT for patients with progressive follicular lymphoma is feasible and may result in prolonged disease-free survival.

Adult↗
PubMed2001

Fibrinogen naples I (B beta A68T) nonsubstrate thrombin-binding capacities.

Fibrinogen Naples I (Bbeta A68T) is characterized by defective thrombin binding and fibrinopeptide cleavage at the fibrinogen substrate site in the E domain. We evaluated the fibrinogen of three homozygotic members of this kindred (II.1, II.2, II.3) who have displayed thrombophilic phenotypes and two heterozygotic subjects (I.1, I.2) who were asymptomatic. Electron microscopy of Naples I fibrin networks showed relatively wide fiber bundles, probably due to slowed fibrin assembly secondary to delayed fibrinopeptide release. We evaluated 125I-thrombin binding to the fibrin from subjects I.1, I.2, II.1, and II.2 by Scatchard analysis with emphasis on the high-affinity site in the D domain of fibrin(ogen) molecules containing a gamma chain variant termed gamma'. Homozygotic subjects II.1 and II.2 showed virtually absent low-affinity binding, consistent with the Bbeta A68T mutation, whereas heterozygotes I.1 and I.2 showed only moderately reduced low-affinity binding. The homozygotes also showed impaired high-affinity thrombin binding, whereas that of the heterozygotes was nearly the same as normal. Genomic sequencing of the gamma' coding sequence (I.2, II.2), ELISA measurements of two gamma' chain epitopes (L2B, gamma'409-412, and IF10, gamma'417-427) (I.2, II.1, II.2, II.3), and mass spectrometry of Naples I fibrinogen (II.2) showed no differences from normal, thus indicating that there were no abnormal structural modifications of the gamma' chain residues in Naples I fibrinogen. However, thrombin reportedly utilizes both of its available exosites for binding to high- and low-affinity sites on normal fibrin, suggesting that binding is cooperative. Thus, reduced high-affinity thrombin binding to homozygotic Naples I fibrin may be related to the absence of low-affinity binding sites.

Binding Sites↗