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Biomedical subjects

A Thomson

Publications and source records attributed to A Thomson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses.

OBJECTIVE: To assess associations between baseline values of four different circulating markers of inflammation and future risk of coronary heart disease, potential triggers of systemic inflammation (such as persistent infection), and other markers of inflammation. DESIGN: Nested case-control comparisons in a prospective, population based cohort. SETTING: General practices in 18 towns in Britain. PARTICIPANTS: 506 men who died from coronary heart disease or had a non-fatal myocardial infarction and 1025 men who remained free of such disease until 1996 selected from 5661 men aged 40-59 years who provided blood samples in 1978-1980. MAIN OUTCOME MEASURES: Plasma concentrations of C reactive protein, serum amyloid A protein, and serum albumin and leucocyte count. Information on fatal and non-fatal coronary heart disease was obtained from medical records and death certificates. RESULTS: Compared with men in the bottom third of baseline measurements of C reactive protein, men in the top third had an odds ratio for coronary heart disease of 2.13 (95% confidence interval 1.38 to 3.28) after age, town, smoking, vascular risk factors, and indicators of socioeconomic status were adjusted for. Similar adjusted odds ratios were 1.65 (1.07 to 2.55) for serum amyloid A protein; 1.12 (0.71 to 1.77) for leucocyte count; and 0.67 (0.43 to 1.04) for albumin. No strong associations were observed of these factors with Helicobacter pylori seropositivity, Chlamydia pneumoniae IgG titres, or plasma total homocysteine concentrations. Baseline values of the acute phase reactants were significantly associated with one another (P<0.0001), although the association between low serum albumin concentration and leucocyte count was weaker (P=0.08). CONCLUSION: In the context of results from other relevant studies these findings suggest that some inflammatory processes, unrelated to the chronic infections studied here, are likely to be involved in coronary heart disease.

Acute-Phase Reaction↗
PubMed2000

Chlamydia pneumoniae IgG titres and coronary heart disease: prospective study and meta-analysis.

OBJECTIVE: To examine the association between coronary heart disease and serum markers of chronic Chlamydia pneumoniae infection. DESIGN: "Nested" case-control analysis in a prospective cohort study and an updated meta-analysis of previous relevant studies. SETTING: General practices in 18 towns in Britain. PARTICIPANTS: Of the 5661 men aged 40-59 who provided blood samples during 1978-80, 496 men who died from coronary heart disease or had non-fatal myocardial infarction and 989 men who had not developed coronary heart disease by 1996 were included. MAIN OUTCOME MEASURES: IgG serum antibodies to C pneumoniae in baseline samples; details of fatal and non-fatal coronary heart disease from medical records and death certificates. RESULTS: 200 (40%) of the 496 men with coronary heart disease were in the top third of C pneumoniae titres compared with 329 (33%) of the 989 controls. The corresponding odds ratio for coronary heart disease was 1.66 (95% confidence interval 1.25 to 2.21), which fell to 1.22 (0.82 to 1.82) after adjustment for smoking and indicators of socioeconomic status. No strong associations were observed between C pneumoniae IgG titres and blood lipid concentrations, blood pressure, or plasma homocysteine concentration. In aggregate, the present study and 14 other prospective studies of C pneumoniae IgG titres included 3169 cases, yielding a combined odds ratio of 1. 15 (0.97 to 1.36), with no significant heterogeneity among the separate studies (chi(2)=10.5, df=14; P>0.1). CONCLUSION: This study, together with a meta-analysis of previous prospective studies, reliably excludes the existence of any strong association between C pneumoniae IgG titres and incident coronary heart disease. Further studies are required, however, to confirm or refute any modest association that may exist, particularly at younger ages.

Adult↗
PubMed2000

An evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter pylori. Canadian Dyspepsia Working Group.

OBJECTIVES: To provide Canadian primary care physicians with an evidence-based clinical management tool, including diagnostic and treatment recommendations, for patients who present with uninvestigated dyspepsia. RECOMMENDATIONS: The management tool has 5 key decision steps addressing the following: (1) evidence that symptoms originate in the upper gastrointestinal tract, (2) presence of alarm features, (3) use of nonsteroidal anti-inflammatory drugs (NSAIDs), (4) dominant reflux symptoms and (5) evidence of Helicobacter pylori infection. All patients over 50 years of age who present with new-onset dyspepsia and patients who present with alarm features should receive prompt investigation, preferably by endoscopy. The management options for patients with uninvestigated dyspepsia who use NSAIDs regularly are: (1) to stop NSAID therapy and assess symptomatic response, (2) to treat with NSAID prophylaxis if NSAID therapy cannot be stopped or (3) to refer for investigation. Gastroesophageal reflux disease can be diagnosed clinically if the patient's dominant symptoms are heartburn or acid regurgitation, or both; these patients should be treated with acid suppressive therapy. The remaining patients should be tested for H. pylori infection, and those with a positive result should be treated with H. pylori-eradication therapy. Those with a negative result should have their symptoms treated with optimal antisecretory therapy or a prokinetic agent. VALIDATION AND EVIDENCE: Evidence for resolution of the dyspepsia symptoms was the main outcome measure. Supporting evidence for the 5 steps in the management tool and the recommendations for treatment were graded according to the strength of the evidence and were endorsed by consensus of committee members. If no randomized controlled clinical trials were available, the recommendations were based on the best available evidence. LITERATURE REVIEW: Evidence was obtained from MEDLINE searches for pertinent articles published from 1966 to October 1999. The searches focused on dyspepsia, diagnosis and treatment. Additional articles were retrieved through a manual search of bibliographies and abstracts from international gastroenterology conferences.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Prospective study of potentially virulent strains of Helicobacter pylori and coronary heart disease in middle-aged men.

BACKGROUND: Studies are needed to test claims that potentially virulent strains of Helicobacter pylori are more strongly related to coronary heart disease (CHD) than are other strains. METHODS AND RESULTS: We measured serum IgG antibodies to mixed H pylori antigens and separately to the virulence-associated H pylori antigen CagA (cytotoxin-associated gene product A) in 505 CHD cases and in 1025 age-matched controls "nested" in a prospective study of 7735 British men (mean duration of follow-up in controls, 16 years). Of the 505 cases, 401 (79%) were seropositive for H pylori antibodies compared with 740 (72%) of the 1025 controls, yielding an odds ratio for CHD of 1.55 (95% CI 1.19 to 2.03), which fell to 1.30 (95% CI 0.88 to 1. 90) after adjustments were made for standard vascular risk factors and indicators of socioeconomic status. Of the CHD cases, 240 (48%) were seropositive for IgG antibodies to CagA compared with 450 (44%) of the controls. When CagA-seropositive individuals were compared with H pylori-seronegative individuals, the odds ratio for CHD was 1. 42 (95% CI 1.06 to 1.91), which fell to 1.10 (95% CI 0.71 to 1.71) after adjustments. In an analysis restricted to the 1141 (75%) H pylori-seropositive participants, the odds ratio for CHD was 1.0 (95% CI 0.78 to 1.29) in CagA-seropositive men. No strong associations were observed between H pylori seropositivity and blood lipids, blood pressure, markers of systemic inflammation, or plasma homocysteine. CONCLUSIONS: H pylori infection is not strongly related to the incidence of CHD in late middle-aged men, and CagA-positive strains appear to be no more strongly related to the disease than other strains. However, further studies are required to confirm or refute the existence of any moderate associations, particularly at younger ages.

Antibodies, Bacterial↗
PubMed2000

Induction of ovulation in women undergoing assisted reproductive techniques: recombinant human FSH (follitropin alpha) versus highly purified urinary FSH (urofollitropin HP).

This multicentre, open, randomized, study compared the efficacy and safety of recombinant follicle stimulating hormone (rFSH; follitropin alpha) with highly purified urinary human FSH (uFSH; urofollitropin HP) in women undergoing ovulation induction for assisted reproductive techniques. Following long down-regulation with buserelin, patients received two ampoules of 75 IU (150 IU) s.c. rFSH or highly purified uFSH for 6 days, after which the dose could be increased until they fulfilled the criteria for human chorionic gonadotrophin (HCG) administration. Of 168 patients recruited, 155 received at least one dose of FSH, and 137 received HCG [68: rFSH (85%); 69: uFSH (92%)]. Following oocyte retrieval and fertilization, up to three embryos were replaced/patient and luteal support was given. The mean number of oocytes retrieved/patient was 10.2 +/- 6.0 for rFSH patients compared with 10.8 +/- 6.1 in the uFSH group (not significant). There was a trend towards fewer ampoules used (22.3 +/- 6.5 versus 24.3 +/- 6.5), higher pregnancy (44.3 versus 41.4%) and live birth rates (33.8 versus 26.7%), as well as a lower miscarriage rate (0.0 versus 16.7%) in favour of rFSH. However, no significant differences in efficacy parameters were recorded. Ovarian hyperstimulation syndrome occurred in 8.6% and 7.9% of rFSH and uFSH patients respectively. In conclusion, this protocol was effective in inducing multiple follicular development and high numbers of oocytes were retrieved with both drugs.

Adolescent↗
PubMed2000

High prevalence of potentially virulent strains of Helicobacter pylori in the general male British population.

BACKGROUND: Strains of Helicobacter pylori that express the cytotoxin associated gene product A (CagA) may be more strongly associated with serious gastric diseases, such as gastric cancer and peptic ulceration, than other strains. Data, however, are sparse on the prevalence, risk factors, and other correlates of these strains in the general population. AIM: To characterise aspects of the seroepidemiology of CagA(+) strains of H pylori in the general British population. METHODS: We measured serum IgG antibodies to mixed H pylori antigens and separately to CagA in 1025 men aged 40-59 years who were randomly selected from a larger group of participants in a community based survey conducted in 18 different British towns. RESULTS: Overall, 44% (95% confidence interval 41-47%) of the men were seropositive to CagA antibodies, representing about 61% (57-65%) of the men seropositive to mixed antigen H pylori. The risk factors for seropositivity to CagA antibodies were similar to those for seropositivity to mixed antigen H pylori, apart from an increased prevalence of reported bedroom sharing in childhood (p<0.01). CONCLUSION: In a nationwide study of potentially virulent H pylori strains, there was a high prevalence of the infection, with some evidence that acquisition of such strains might occur earlier in life than other strains.

Aged↗
PubMed2000

Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families.

BACKGROUND: Respiratory syncytial virus (RSV) infects nearly all children by the end of their second winter. Why some develop bronchiolitis is poorly understood; it is not known whether there is a genetic component. The pathological features include neutrophil infiltration and high levels of interleukin 8 (IL-8), a potent neutrophil chemoattractant. METHODS: Common genetic variants of the promoter region of the IL-8 gene were identified by sequencing DNA from 36 healthy individuals. Genetic correlates of IL-8 production were assessed using whole blood from 50 healthy subjects. To investigate genetic correlates of disease severity 117 nuclear families were recruited in which a child had required hospital admission for RSV bronchiolitis. RESULTS: A common single nucleotide polymorphism (allele frequency 0.44) was identified 251 bp upstream of the IL-8 transcription start site. The IL8-251A allele tended to be associated with increased IL-8 production by lipopolysaccharide stimulated whole blood (p=0.07). Using the transmission disequilibrium test, the frequency of this allele was significantly increased in infants with bronchiolitis (transmission = 62% (95% confidence interval (CI) 53 to 71), p=0.014) and particularly in those without known risk factors (transmission = 78% (95% CI 62 to 93), p=0.004). CONCLUSION: Disease severity following RSV infection appears to be determined by a genetic factor close to the IL-8 gene. Further analysis of this effect may elucidate causal processes in the pathogenesis of RSV bronchiolitis.

Alleles↗
PubMed2000

[Executive cognitive alteration of prefrontal type in patients with mesial temporal lobe epilepsy].

This study examines the performance on executive function--classically considered as purported by the frontal lobes--in patients with temporal lobe epilepsy (TLE). Two groups of patients were evaluated: one consisted of 16 TLE patients and the other comprised 12 patients with primary generalised epilepsy (PGE). The Wisconsin Card Sorting Test (WCST) was used as a measure of executive function. Results demonstrated that performance on the WCST was remarkably defective in the TLE group, showing a pattern suggestive of frontal like executive dysfunction in a 75% of the patients, against the 17% of the PGE group (p < 0.001). Impairment was evident when number of categories achieved (p < 0.05), perseverative errors (p < 0.001) and perseverative responses (p < 0.001) were considered. Clinical and theoretical significance of these findings may reflex the executive dysfunction of the mesial temporal lobe region as part of the temporo-frontal circuit.

Adult↗
PubMed1999

Clinicopathologic findings of recurrent primary sclerosing cholangitis after orthotopic liver transplantation.

Whether primary sclerosing cholangitis (PSC) occurs after orthotopic liver transplantation is controversial, largely because the pre-transplant diagnosis of PSC is based on nonspecific radiological and histological findings. We reviewed clinical, radiological, and histological records of 53 patients who underwent liver transplantation for PSC between 1985 and 1998. Three patients with patent hepatic arteries and no evidence of chronic rejection had radiological and histological findings that may have been due to recurrent PSC. Bile duct stricturing in these patients proved permanent and progressive and affected both the quality of life and graft survival. The first patient, who is 110 months after transplantation, has had repeated episodes of cholangitis for the last year. The second patient underwent excision of a strictured hepatic duct 45 months after transplantation and was ultimately retransplanted 95 months after initial transplantation. The third patient underwent left hemihepatectomy of an atrophied lobe 50 months after transplantation. Although the patient population assessed in this study is limited, putative recurrent PSC in the allografts has led either to graft loss or to clinically significant hepatobiliary complications of the graft.

Adolescent↗
PubMed1999

Chimerism and xenotransplantation. New concepts.

In both transplant and infectious circumstances, the immune response is governed by migration and localization of the antigen. If the antigenic epitopes of transgenic xenografts are sufficiently altered to avoid evoking the destructive force of innate immunity, the mechanisms of engraftment should be the same as those that permit the chimerism-dependent immunologic confrontation and resolution that is the basis of allograft acceptance. In addition to "humanizing" the epitopes, one of the unanswered questions is whether the species restriction of complement described in 1994 by Valdivia and colleagues also necessitates the introduction of human complement regulatory genes in animal donors. Because the liver is the principal or sole source of most complement components, the complement quickly is transformed to that of the donor after hepatic transplantation. Thus, the need for complementary regulatory transgenes may vary according to the kind of xenograft used. Much evidence shows that physiologically important peptides produced by xenografts (e.g., insulin, clotting factors, and enzymes) are incorporated into the metabolic machinery of the recipient body. To the extent that this is not true, xenotransplantation could result in the production of diseases that are analogous to inborn errors of metabolism. In the climate of pessimism that followed the failures of baboon to human liver xenotransplantation in 1992-1993, it seemed inconceivable that the use of even more discordant donors, such as the pig, could ever be seriously entertained; however, this preceded insight into the xenogeneic and allogeneic barriers that has brought transplantation infectious immunity to common ground. With this new insight and the increasing ease of producing transgenic donors, the goal of clinical xenotransplantation may not be so distant.

Animals↗
PubMed1999

Gene therapy in transplantation.

Facilitation of solid organ and cell transplantation depends on metabolic and immunologic factors that can be manipulated ex vivo and in vivo using gene transfer technology. Vectors have been developed which can optimally transfer relevant genes to various tissues and organs. Interventions aimed at promoting tissue preservation before transplantation, prevention of oxidative stress and immunological rejection have recently become attractive options using viral and nonviral gene delivery vehicles. Further understanding of the mechanisms involved in tolerance induction as well as the facilitation of xenogeneic engraftment have made possible a variety of avenues that can be exploited using gene transfer technology.

Animals↗