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Biomedical subjects

S Campbell

Publications and source records attributed to S Campbell.

At least 91 records · Page 5Linked to original sources
PubMed2001

Is neutropenia required for effective maintenance of remission during azathioprine therapy in inflammatory bowel disease?

BACKGROUND: Azathioprine is an effective treatment for maintaining remission in inflammatory bowel disease (IBD). It is a matter of debate as to whether neutropenia is required during azathioprine therapy to achieve more effective disease remission. We evaluated whether neutropenia during azathioprine therapy reduced relapse rates in IBD patients. PATIENTS AND METHODS: This retrospective study was based on a total of 173 IBD (96 Crohn's disease (CD), 77 ulcerative colitis (UC)) patients who were stable on azathioprine for a minimum of 6 months. Median duration of follow-up was 4.0 years (range 0.6-21 years). The lowest neutrophil counts during treatment for these patients were recorded. Relapse rates per year of follow-up were compared in non-neutropenic patients (neutrophil count > 2.5 x 10(9), n = 129) and neutropenic patients (neutrophil count < or = 2.5 x 10(9), n = 44) groups, and survival curves for cumulative remission rates compared by log-rank test. RESULTS: Mean relapse rate per year of follow-up for the non-neutropenic group was 0.19/year (SD = 0.37/year) compared with the neutropenic group 0.28/year (SD = 0.43/year) (P = NS). Analysis was performed on UC and CD subgroups, and relapse rates were not significantly different. The cumulative remission per cent determined by Kaplan-Meier survival analysis showed no difference between non-neutropenic and neutropenic groups by log-rank analysis, for UC and CD as well as for all IBD patients. CONCLUSION: Neutropenia < or = 2.5 x 10(9) while on azathioprine does not reduce the relapse rates of IBD patients who were established on azathioprine therapy compared with neutrophil counts > 2.5 x 10(9).

Adolescent↗
PubMed2001

Effective maintenance of inflammatory bowel disease remission by azathioprine does not require concurrent 5-aminosalicylate therapy.

OBJECTIVES: To assess the effect of 5-aminosalicylate treatment in conjunction with azathioprine on remission maintenance in inflammatory bowel disease patients. METHOD: This retrospective study was based on a total of 186 inflammatory bowel disease patients (104 with Crohn's disease; 82 with ulcerative colitis), who were stable on azathioprine for a minimum of 6 months. The median duration of follow-up was 4.3 years (range 0.6-15.5 years). Relapse rates per year of follow-up were compared in an azathioprine + 5-aminosalicylate group (n = 103) and an azathioprine alone group (n = 83); survival curves for cumulative remission rates were compared by log-rank test. Discontinuation of azathioprine in both groups was also recorded, as was the incidence of malignancy. RESULTS: In ulcerative colitis patients (n = 82), mean relapse rates for the azathioprine + 5-aminosalicylate group were 0.21/year compared with 0.19/year for the azathioprine alone group (P = not significant). In Crohn's disease patients (n = 104), mean relapse rates for the azathioprine + 5-aminosalicylate group were 0.27/year compared with 0.3/year for the azathioprine alone group (P = not significant). The cumulative remission percentage (determined from time to first relapse) was used in Kaplan-Meier survival analysis and showed no difference between the azathioprine + 5-aminosalicylate group and the azathioprine alone group by log-rank analysis, for ulcerative colitis and Crohn's disease as well as for all inflammatory bowel disease patients. Concurrent use of 5-aminosalicylates was no more frequent in patients who discontinued azathioprine due to adverse events. The only malignancy recorded was Waldenström's macroglobulinaemia after 7 years of azathioprine therapy. CONCLUSION: Concurrent use of 5-aminosalicylate drugs did not reduce the relapse rates of inflammatory bowel disease patients who were established on azathioprine therapy. The use of 5-aminosalicylate drugs did not lead to any increase in discontinuation of azathioprine due to adverse events.

Adolescent↗
PubMed2001

Clinical governance: a convincing strategy for quality improvement?

Clinical governance is a new policy introduced by the UK government to improve quality of care in the National Health Service; it imposes a "duty of quality" on all NHS organisations, and aims to bring together managerial, organisational and clinical approaches to improving quality of care. Infrastructures have been established to support quality improvement in NHS organisations and priorities for quality improvement have been established. Initial approaches are largely educational. However, information on quality of care is starting to be shared, and experiments are being conducted with a range of financial and contractual incentives for quality improvement. For widespread cultural change to occur, a "no blame" approach to quality improvement will be necessary; this may be incompatible with the need to identify and eliminate bad practice. Other tensions include the rapid pace of change being centrally driven and uneven development of the infrastructure to support clinical governance. What has not yet been shown is that quality of care has improved. It is too early to say this yet. Given the magnitude both of the vision and the work required, it is unlikely that change will be rapid, or seen on a widespread scale.

Clinical Competence↗
PubMed2001

A novel in vitro co-culture system for the study of maternal decidual endothelial cell-trophoblast interactions in human pregnancy.

Investigation of the pathophysiology of pre-eclampsia (characterised by insufficient invasion of the intrauterine vasculature by cytotrophoblasts) has been hampered by the absence of a suitable animal model, and ethical constraints in clinical studies. We have developed a novel in vitro human cell co-culture system allowing direct assessment of cytotrophoblast invasion of a decidual endothelial cell monolayer from the abluminal side, as occurs in vivo. This model will facilitate detection, at the cellular level, of abnormal endothelial cell-trophoblast functional interactions in pre-eclampsia and other pregnancy disorders with abnormal placentation.

Cell Communication↗
PubMed2001

Human immunodeficiency virus type 1 N-terminal capsid mutants that exhibit aberrant core morphology and are blocked in initiation of reverse transcription in infected cells.

A group of conserved hydrophobic residues faces the interior of the coiled-coil-like structure within the N-terminal domain of the human immunodeficiency virus type 1 (HIV-1) capsid protein (CA). It has been suggested that these residues are important for maintaining stable structure and functional activity. To investigate this possibility, we constructed two HIV-1 clones, in which Trp23 or Phe40 was changed to Ala. We also constructed a third mutant, D51A, which has a mutation that destroys a salt bridge between Pro1 and Asp51. All three mutants are replication defective but produce virus particles. Mutant virions contain all of the viral proteins, although the amount and stability of CA are decreased and levels of virion-associated integrase are reduced. The mutations do not affect endogenous reverse transcriptase activity; however, the mutants are blocked in their ability to initiate reverse transcription in infected cells and no minus-strand strong-stop DNA is detected. The defect in reverse transcription is associated with striking defects in the morphology of mutant virus cores, as determined by transmission electron microscopy. Our data indicate that the mutations made in this study disrupt CA structure and prevent proper maturation of virus cores. We propose that this results in a defect in core stability or in an early postentry event preceding reverse transcription.

Gene Products, gag↗
PubMed2001

Acute hospital admissions from nursing homes: some may be avoidable.

A retrospective survey of acute hospital admissions from nursing homes over a year to a district hospital revealed high overall hospital admission rates and wide variations of admission rates from similar homes. Medical admissions dominated, infections and poorly controlled heart failure being notably common. A significant proportion of admissions may have been avoided by active chronic disease management, together with better information for doctors responding to emergency calls and specialist support programmes facilitating in situ treatment.

Acute Disease↗
PubMed2001

Aedes (Finlaya) japonicus (Diptera: Culicidae), a newly recognized mosquito in the United States: analyses of genetic variation in the United States and putative source populations.

Introduction of potential disease vectors into a new geographic area poses health risks to local human, livestock, and wildlife populations. It is therefore important to gain understanding of the dynamics of these invasions, in particular its sources, modes of spread after the introduction, and vectorial potential. We studied the population genetics of Aedes (Finlaya) japonicus japonicus (Theobald), an Asian mosquito that was recognized for the first time in the United States in 1998. We examined patterns of genetic diversity using random amplified polymorphic DNA and sequences of ND4 of mtDNA by comparing samples from populations spanning the range of this mosquito in Japan (six samples) and the United States (nine samples) as well as specimens intercepted in New Zealand in 1999. We found geographically differentiated populations in Japan, indicating limited gene flow even on small spatial scales. In the United States, we found evidence of significant genetic differentiation between samples from New York, Connecticut, and New Jersey and those from mid-Pennsylvania and Maryland. We were unable to pinpoint the source location(s) in Japan, although some of the U.S. samples are genetically close to samples from south Honshu and western Kyushu. Further studies should include samples from Korean populations. Distinct genetic signatures in U.S. populations undergoing expansion suggest the possibility of local increases in genetic diversity if and where they meet.

Aedes↗
PubMed2001

Dementia with Lewy bodies: clinical features and treatment.

Dementia with Lewy bodies (DLB) accounts for 15 to 20% of late-onset dementias. The overlap of cognitive symptoms, neuropsychiatric features, parkinsonism and severe sensitivity to antipsychotic drugs raise a number of key management issues. The neurochemical profile of DLB provides a good theoretical rationale for the potential value of cholinesterase inhibitor therapy, which is supported by clinical evidence from a number of case series and one placebo-controlled double-blind trial. It appears that cholinesterase inhibitor treatment is well tolerated and improves fluctuating confusion, cognition and psychotic symptoms; however, the evidence can still only be considered preliminary and a further double-blind study is imperative. Given the high prevalence of severe sensitivity to antipsychotic drugs in patients with DLB, their role in the treatment of psychiatric symptoms and behavioural problems is uncertain, although a small case report literature indicates that some patients may benefit. On the current balance of evidence, prescription of antipsychotic agents to patients with DLB is not recommended, although further studies focussing on patients with severe and intractable neuropsychiatric symptoms are required. Provisional case series indicate a high degree of motor response to levodopa therapy, although controlled trials are a priority to carefully evaluate the benefits in the context of possible adverse effects, such as the exacerbation of psychosis.

Aged↗
PubMed2001

Spontaneous chronic corneal epithelial defects (SCCED) in dogs: clinical features, innervation, and effect of topical SP, with or without IGF-1.

PURPOSE: To delineate the clinical features and alterations in innervation and substance P (SP) content in spontaneous chronic corneal epithelial defects (SCCED) in dogs and to conduct a preliminary investigation evaluating the efficacy of topical SP, with or without insulin-like growth factor (IGF)-1, in the treatment of this disorder. METHODS: Complete ophthalmic examinations, including Cochet-Bonnet aesthesiometry, were performed in 45 canine patients that had spontaneous corneal epithelial defects of at least 3 weeks' duration and with no identifiable cause. Eighteen patients had superficial keratectomies performed, and the corneal nerves were labeled immunohistochemically with antibodies against protein gene product (PGP)-9.5, SP, vasoactive intestinal peptide (VIP), and tyrosine hydroxylase (TH). Relative fiber densities were assessed qualitatively and quantitatively. Corneal epithelial cell and tear SP contents were determined in affected and normal dogs by an enzyme immunoassay. A preliminary open-label treatment trial of topical SP, with and without IGF-1, was conducted in 21 dogs. RESULTS: The duration of the erosion before admittance into the study was a mean of 9.22 weeks (range, 3-52). The average patient was middle aged (mean, 9.25 +/- 1.85 years [SD]); no sex predisposition of the disease was identified. Boxers, golden retrievers, and keeshonds were overrepresented when compared with the normal hospital population. Corneal sensation was normal. Marked alterations in corneal innervation were identified in affected dogs with abnormal increased SP and calcitonin gene-related peptide (CGRP)-immunoreactive nerve plexuses identified surrounding the periphery of the epithelial defect. The SP content of epithelial cells surrounding the defect increased, whereas the tear SP content remained unchanged. Of the canine patients treated with SP, with or without IGF-1, 70% to 75% had complete healing of the defect. CONCLUSIONS: This idiopathic spontaneous corneal disease in dogs shares clinical features with chronic epithelial defects in humans. The presence of marked alterations in peptidergic innervation and positive response to topical therapy with SP suggest that SP plays a critical role in corneal wound-healing processes.

Administration, Topical↗
PubMed2000

The Ras/p120 GTPase-activating protein (GAP) interaction is regulated by the p120 GAP pleckstrin homology domain.

Pleckstrin homology domains are structurally conserved functional domains that can undergo both protein/protein and protein/lipid interactions. Pleckstrin homology domains can mediate inter- and intra-molecular binding events to regulate enzyme activity. They occur in numerous proteins including many that interact with Ras superfamily members, such as p120 GAP. The pleckstrin homology domain of p120 GAP is located in the NH(2)-terminal, noncatalytic region of p120 GAP. Overexpression of the noncatalytic domains of p120 GAP may modulate Ras signal transduction pathways. Here, we demonstrate that expression of the isolated pleckstrin homology domain of p120 GAP specifically inhibits Ras-mediated signaling and transformation but not normal cellular growth. Furthermore, we show that the pleckstrin homology domain binds the catalytic domain of p120 GAP and interferes with the Ras/GAP interaction. Thus, we suggest that the pleckstrin homology domain of p120 GAP may specifically regulate the interaction of Ras with p120 GAP via competitive intra-molecular binding.

3T3 Cells↗
PubMed2000

Pressurized fluid extraction of nonpolar pesticides and polar herbicides using in situ derivatization

Analysis of polar acidic herbicides has traditionally presented a challenge because of their strong adsorption to and ionic interactions with soil. One approach which has been successful for extraction of these polar compounds from soil is supercritical fluid extraction (SFE) coupled with in situ derivatization. This technique involves the addition of common derivatization reagents directly into the extraction chamber, where the acid herbicides are derivitized to extractable esters or ethers. This study describes the application of an in situ derivatization technique to pressurized fluid extraction (PFE) for the herbicides 2,4-D, 2,4,5-T, dicamba, silvex, trichlopyr, and bentazone. The efficiency of in situ derivatization PFE for these analytes is compared with a conventional basic extraction method followed by ex situ derivatization. The variables of temperature, pressure, static extraction time, and derivatization-reagent amount were optimized for recovery of these analytes from soil. Average recovery for these six analytes was 107% for in situ derivatization PFE from spiked sand, 93% for the same method from a high-concentration spiked soil (50 mg/kg), and 68% for the optimized in situ derivatization PFE method from low-concentration soil (0.5 mg/kg). The in situ derivatization PFE method has substantial advantages of simplicity of methodology and reduction in extraction time compared with the conventional technique. A second in situ derivatization PFE strategy was investigated using sodium EDTA in the extraction chamber for the extraction of 2,4-D from soil. Preliminary results demonstrate improved recovery with the use of Na4EDTA. Extraction efficiency of PFE for nonpolar organochlorine insecticides and slightly polar triazine herbicides from soil is also presented and compared with that of Soxhlet extraction.

Journal Article↗
PubMed2000

Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis.

Ankylosing spondylitis (AS) is a common and highly familial rheumatic disorder. The sibling recurrence risk ratio for the disease is 63 and heritability assessed in twins >90%. Although MHC genes, including HLA-B27, contribute only 20-50% of the genetic risk for the disease, no non-MHC gene has yet been convincingly demonstrated to influence either susceptibility to the disease or its phenotypic expression. Previous linkage and association studies have suggested the presence of a susceptibility gene for AS close to, or within, the cytochrome P450 2D6 gene (CYP2D6, debrisoquine hydroxylase) located at chromosome 22q13.1. We performed a linkage study of chromosome 22 in 200 families with AS affected sibling-pairs. Association of alleles of the CYP2D6 gene was examined by both case-control and within-family means. For case-control studies, 617 unrelated individuals with AS (361 probands from sibling-pair and parent-case trio families and 256 unrelated non-familial sporadic cases) and 402 healthy ethnically matched controls were employed. For within-family association studies, 361 families including 161 parent-case trios and 200 affected sibling-pair families were employed. Homozygosity for poor metabolizer alleles was found to be associated with AS. Heterozygosity for the most frequent poor metabolizer allele (CYP2D6*4) was not associated with increased susceptibility to AS. Significant within-family association of CYP2D6*4 alleles and AS was demonstrated. Weak linkage was also demonstrated between CYP2D6 and AS. We postulate that altered metabolism of a natural toxin or antigen by the CYP2D6 gene may increase susceptibility to AS.

Alleles↗
PubMed2000

Benign ovarian cysts and ovarian cancer: a cohort study with implications for screening.

BACKGROUND: Whether some benign ovarian cysts can develop into cancerous cysts is not known. If a large proportion of ovarian cancers arose in this way, it might be possible to remove the benign cysts in a screening programme before they became malignant. We used follow-up data from a cohort of 5479 self-referred women without symptoms, who participated in a ultrasonographic-screening trial for early ovarian cancer between June, 1981, and August, 1987. We assessed whether the removal of persistent ovarian cysts from these women was associated with a reduction in the expected number of deaths from ovarian cancer in the cohort as a whole. METHODS: The expected number of deaths from all causes, all cancers, and ovarian, breast, and colorectal cancers were calculated for the study cohort by the standard life-table method. The actual number of deaths and each cause were obtained and the proportional mortality ratio was calculated for each cause of death. FINDINGS: 5135 (95%) of the participants in the original trial were traced. During the screening, five of these women were found to have stage I epithelial ovarian cancer and 88 had benign epithelial ovarian tumours. The number of reported deaths from all causes (387 [50% of expected]), all cancers (221 [71%]), and ovarian cancer (22 [90%]) was lower than expected because of the "healthy-volunteer effect". Proportional mortality ratios were 100% (by definition) for all cancers, 141% for breast cancer, 128% for ovarian cancer (95% CI 87.7-187.6, p=0.19), 84% for colorectal cancer, and 48% for lung cancer. INTERPRETATION: The removal of persistent ovarian cysts was not associated with a decrease in the proportion of expected deaths from ovarian cancer relative to other cancers during follow-up. For population-based screening of healthy women without a family history of ovarian cancer, a screening test is required that is specific and sensitive to early malignant disease, and inexpensive.

Adult↗
PubMed2000

Adhesion and proliferation of corneal epithelial cells on self-assembled monolayers.

The effect of surface chemistry on the proliferation and adhesion of SV-40 human corneal epithelial cells was investigated. The surface chemistry of substrates was controlled by the deposition of self-assembled monolayers (SAMs) terminated with the following functional groups: -CF3, -CH3, -CO(2)H, and -NH(2). SAMs of alkanethiols on gold and of alkylsiloxanes on SiOx were included in the study. Comparisons are made between different types and functionalities of SAMs and between SAM-covered substrates and tissue culture polystyrene. Adhesion assays were performed after incubation of the cells for 1 h in 10% fetal bovine serum and in serum-free conditions. The cellular response was found to be a function of surface chemistry and the presence of exogenous proteins. The number of cells that adhered to most of the SAMs in 10% serum and in serum-free conditions was not significantly different from the number of cells that adhered to TCPS. Proliferation assays were carried out in 10% serum and in 0.5% serum. Cell behavior was influenced by surface chemistry but did not deviate significantly from the behavior on TCPS for most of the SAMs. Serum level did not play a major role in cell proliferation. Our data establish the expected behaviors for a corneal epithelial cell line under defined conditions on specific surfaces.

Adhesiveness↗
PubMed2000

Analyzing the influence of PrP primary structure on prion pathogenesis in transgenic mice.

Expression of prion protein (PrP) genes in transgenic (Tg) mice has been an extremely effective means of studying human and animal prion diseases. Indeed, much of what we currently understand about the molecular basis of prion pathogenesis derives from such studies. Despite these advances, the emergence of a new variant of Creutzfeldt-Jakob disease (vCJD), apparently the human manifestation of bovine spongiform encephalopathy (BSE), demonstrates that our understanding of the factors controlling prion transmission is far from complete. We review studies in Tg mice that have addressed issues of prion strains and species barriers and have provided insights into mechanisms of prion propagation. The goal of future investigation will be to determine the interplay between PrP primary structure and conformation in determining prion transmission barriers and we discuss some ongoing transgenic studies designed to address these issues.

Amino Acid Sequence↗