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Biomedical subjects

D Carrington

Publications and source records attributed to D Carrington.

At least 37 records · Page 2Linked to original sources

Reference laboratory surveillance of syphilis in England and Wales, 1994 to 1996.

Routine surveillance of syphilis of public health importance (infectious, congenital, and neurosyphilis) began in England and Wales in 1994, using reports from six PHLS laboratories that undertook serological and other reference work. One hundred and thirty-one cases were reported in the first two years, including 100 cases of infectious syphilis, with all regions reporting some infectious syphilis. Reports from PHLS laboratories represented one sixth of the number of cases seen in genitourinary clinics (KC60 data), but both systems produced comparable results. Laboratory reports provided more data on risk factors, which were not available elsewhere. This study documents the risk in England and Wales from infections originating in eastern Europe, where sexually transmitted infections including syphilis have reached epidemic proportions. Forty-five per cent of cases of infectious syphilis were reported to have been acquired in the United Kingdom (UK) and 59% of people with infectious syphilis were reported to have been born in the UK. Twenty per cent of the infectious cases were associated directly or indirectly with transmission in Russia or elsewhere in eastern Europe. The majority of infectious cases were from the white ethnic group. Eighty-five per cent of cases of infectious syphilis were reported to have been acquired heterosexually; 26% of male cases were reported to have been acquired homosexually. The PHLS laboratory reporting system is now well established, and could usefully be expanded to include other, non PHLS, laboratories that undertake reference work. It has the capacity to detect changes in the national epidemiology of syphilis, including imported infections.

Adult↗

Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction.

BACKGROUND: The clinical significance of the association between elevated anti-Chlamydia pneumoniae (Cp) antibody titres and coronary heart disease (CHD) is unclear. We explored the relationship between antibodies against Cp and future cardiovascular events in male survivors of myocardial infarction (MI). The effect of azithromycin antibiotic therapy was assessed in a subgroup of post-MI patients. METHODS AND RESULTS: We screened 220 consecutive male survivors of MI for anti-Cp antibodies. Of these, 213 patients were stratified into three groups: group Cp-ve (n=59), no detectable Cp antibodies; group Cp-I (n=74), intermediate titres of 1/8 to 1/32 dilution; and group Cp+ve (n=80), seropositive at > or = 1/64 dilution. Patients with persisting seropositivity of > or = 1/64 were randomized to either oral azithromycin (Cp+ve-A, 500 mg/d for 3 days [n=28] or 500 mg/d for 6 days [n=12]) or placebo (Cp+ve-P, n=20). Cp+ve-NR (n=20) represented patients not recruited into the antibiotic trial. The incidence of adverse cardiovascular events (over a mean follow-up period of 18+/-4 months) was recorded and shown to increase with increasing anti-Cp titre: Cp-ve, n=4 (7%); Cp-I, n=11 (15%); Cp+ve-NR, n=6 (30%); and Cp+ve-P, n=5 (25%). Cp+ve-NR and Cp+ve-P groups had a fourfold-increased risk for adverse cardiovascular events compared with the Cp-ve group (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.2 to 15.5; P=.03). In contrast, the OR for cardiovascular events in patients receiving azithromycin (Cp+ve-A, single or double course) was the same as in the Cp-ve group (OR, 0.9; 95% CI, 0.2 to 4.6, P=NS). Patients receiving azithromycin were more likely to experience a decrease in IgG anti-Cp titres than were those in the placebo group (P=.02). CONCLUSIONS: An increased anti-Cp antibody titre may be a predictor for further adverse cardiovascular events in post-MI patients. Taking a short course of azithromycin may lower this risk, possibly by acting against Cp.

Administration, Oral↗

Assessment of pain in herpes zoster: lessons learned from antiviral trials.

Pain typically accompanies acute herpes zoster and, in a proportion of patients, it persists well beyond rash healing. Pain must therefore be analyzed in trials of antiviral agents in herpes zoster, but different methods have been used to analyze pain in recent published trials. These reports are reviewed and their methodological strengths and weaknesses examined. Based on this review, recommendations for the design and analysis of future trials of antiviral agents in herpes zoster are proposed. The principal recommendation is that antiviral efficacy should be evaluated both by distinguishing post-herpetic neuralgia from acute pain and by considering pain as a continuum. The primary endpoint should address both the prevalence and duration of post-herpetic neuralgia and should be examined in those patients who have post-herpetic neuralgia. Adopting the proposed recommendations in design and analysis of future trials should facilitate comparison across trials of the efficacy of antiviral agents in the treatment of herpes zoster.

Antiviral Agents↗

Molecular epidemiology of varicella-zoster virus in East London, England, between 1971 and 1995.

The molecular epidemiology of varicella-zoster virus in London, England, between 1971 and 1995 was examined by using two informative polymorphic markers, variable repeat region R5 and a BglI restriction site in gene 54. Viruses from 105 cases of chickenpox and 144 of zoster were typed. Two alleles of R5, A and B, were found at prevalences of 89 and 6%, respectively. No difference in allele frequency between the zoster and chickenpox cases was found, and no change in the frequencies of these alleles was observed to occur over time. By contrast, a BglI restriction site (BglI+) was found with increasing frequency over time among cases of varicella (P < 0.005) and, to a lesser extent, cases of zoster. The BglI+ polymorphism was strongly associated (P < 0.0005) with zoster in subjects who had immigrated to the United Kingdom from countries with low adult immunity to varicella (LAIV). Sixty-three percent of the subjects with zoster who had emigrated from countries with LAIV carried the BglI+ virus, in contrast to 10% of adults who had grown up in countries with high adult immunity to varicella. The significance of these data, in view of the changing epidemiology of chickenpox, is discussed.

Adult↗

Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors.

OBJECTIVE: To investigate the relation between seropositivity to chronic infections with Helicobacter pylori and Chlamydia pneumoniae and both coronary heart disease and cardiovascular risk factors. DESIGN: Cross sectional study of a population based random sample of men. Coronary heart disease was assessed by electrocardiography, Rose angina questionnaire, and a history of myocardial infarction; serum antibody levels to H pylori and C pneumoniae were measured, risk factor levels determined, and a questionnaire administered. SETTING: General practices in Merton, Sutton, and Wandsworth, south London. SUBJECTS: 388 white south London men aged 50-69. MAIN OUTCOME MEASURES: Evidence of coronary risk factors and infection with H pylori or C pneumoniae. RESULTS: 47 men (12.1%) had electrocardiographic evidence of ischaemia or infarction. 36 (76.6%) and 18 (38.3%) were seropositive for H pylori and C pneumoniae, respectively, compared with 155 (45.5%) and 62 (18.2%) men with normal electrocardiograms. Odds ratios for abnormal electrocardiograms were 3.82 (95% confidence interval 1.60 to 9.10) and 3.06 (1.33 to 7.01) in men seropositive for H pylori and C pneumoniae, respectively, after adjustment for a range of socioeconomic indicators and risk factors for coronary heart disease. Cardiovascular risk factors that were independently associated with seropositivity to H pylori included fibrinogen concentration and total leucocyte count. Seropositivity to C pneumoniae was independently associated with raised fibrinogen and malondialdehyde concentrations. CONCLUSIONS: Both H pylori and C pneumoniae infectins are associated with coronary heart disease. These relations are not explained by a wide range of confounding factors. Possible mechanisms include an increase in risk factor levels due to a low grade chronic inflammatory response.

Aged↗

The detection of HIV-1 proviral DNA by PCR in clotted blood specimens.

Six hundred and ninety-two specimens, each consisting of a suspension of the residual free cells in samples of clotted blood (but not the clots themselves) from 680 patients at high risk for exposure to human immunodeficiency virus (HIV), were tested by a nested polymerase chain reaction (PCR) procedure which had been optimized to give a sensitivity of detection of one copy of HIV-1 proviral plasmid DNA, and the results were compared to those of testing for antibody to HIV on the same specimens. Fifty-one of the specimens were positive for antibody to HIV and 49 of these were also positive by the PCR; the two samples which gave discordant results were found to be PCR-positive when the test was repeated on DNA extracted from the clots themselves. Two specimens were found to be negative for antibody to HIV but were positive by the PCR (53 positive specimens in all). Direct sequencing of the PCR DNA products confirmed their specificity in all cases and demonstrated that no two patients gave the same predicted amino acid sequence for the V3 loop region. The sequences revealed both European/North American and African motifs at the crown of the V3 loop thus indicating a diversity of HIV strains in the SW Thames Region of South London. The results show that the confirmatory PCR for HIV-1 can be carried out efficiently on the same clotted blood specimens as used for routine HIV serology on patients undergoing diagnostic evaluation.

Africa↗

Chlamydia pneumoniae: risk factors for seropositivity and association with coronary heart disease.

BACKGROUND: Two studies have suggested that seropositivity for Chlamydia pneumoniae (C. pneumoniae) is a risk factor for coronary heart disease (CHD) but the association remains tenuous. Further data is required in other populations to consolidate this observation. AIMS: Initially to determine descriptive risk factors for C. pneumoniae seropositivity in a general population sample and subsequently to examine the relation of seropositivity for this organism to CHD for the first time in a British population. SETTING: A single general practice health screening clinic and a cardiology clinic involving patients predominantly residing in south London and Surrey. SUBJECTS: 210 consecutive caucasian men (62%) and women (38%) aged 18-79 including 67 men aged 45-65. This latter group acting as controls were then also compared with 103 consecutive males aged 45-65 with angiographically confirmed coronary heart disease. METHODS: A questionnaire was administered by a research nurse and serum was analysed for IgG and IgA against C. pneumoniae and other Chlamydiae by a microimmunofluorescence test. Serum was said to be low positive at a specific IgG antibody titre of 16-32, and high positive if 64 or greater. RESULTS: Amongst the general practice health screening clinic population 14 subjects (7%) were excluded due to possible cross-reactivity with other Chlamydia species (predominantly C. trachomatis). Of the remaining 196 subjects, 13 (6%) had high positive C. pneumoniae IgG titres, 68 (35%) had low titres and 125 had no detectable antibody. After adjustment for sex, age, smoking history, social class and family size only one risk factor for high positive titres in this group was identified, which was the number of children currently living in the home (OR 2.29 (1.09-4.80), P = 0.03). No factors were significantly related to low titres. 22/100 (22%) cases with coronary heart disease and 3/64 (4.7%) of controls had high positive IgG titres for C. pneumoniae. Similarly 21% of cases and 9.4% of controls had positive C. pneumoniae specific IgA serology. 45% of cases and 44% of controls had low C. pneumoniae IgG titres. The association of CHD with a C. pneumoniae IgG titre of 64 or above was independent of all risk factors (OR 7.4 (1.7-33.1), P < 0.01). CONCLUSION: Serological evidence of C. pneumoniae infection is common amongst healthy British subjects. Smoking and social class are not important confounding variables in this study. Reinfection from contact with infected children in the home may be important in inducing higher titres in some subjects. These higher titres are more prevalent in subjects with coronary heart disease in the U.K. as reported in Finland and the U.S.A., and provide further evidence that C. pneumoniae may be important in the pathogenesis of this condition in these populations.

Adolescent↗

Three weeks of ganciclovir for cytomegaloviraemia after allogeneic bone marrow transplantation.

Cytomegaloviraemia diagnosed by early antigen detection or conventional viral culture from blood occurred 7-71 days (median 41 days) after transplant in 25 of 38 consecutive patients undergoing bone marrow transplantation (BMT) from HLA-identical siblings for haematological malignancies where patient and/or donor were CMV-seropositive. Prophylactic ganciclovir, high-dose intravenous acyclovir or immunoglobulin were not administered. Viraemia was treated with a short 3-week course of ganciclovir (10 mg/kg x 1 week, 5 mg/kg x 2 weeks). Clearance of viraemia occurred 3-47 days (median 6 days) after starting anti-viral therapy in 20 patients (18 with ganciclovir, 2 with foscarnet), and before therapy in 3 patients. The remaining 2 patients received inadequate anti-viral therapy for various reasons and died of CMV pneumonitis. There was no clinical evidence of CMV disease in the 13 patients who did not develop viraemia. One patient treated with ganciclovir before adequate haematological recovery died of graft failure. A second episode of viraemia occurred in four patients, and a third in one. We conclude that a short 3-week course of ganciclovir is adequate in most patients developing cytomegaloviraemia after allogeneic BMT. Treatment is not necessary in all patients but some inadequately treated patients develop CMV disease. Ganciclovir is tolerated well but may cause severe myelosuppression if used prior to adequate marrow recovery.

Adolescent↗

Association of cytomegalovirus infection with post-transplantation cardiac rejection as studied using the polymerase chain reaction.

The relationship between cytomegalovirus (CMV) infection and cardiac allograft rejection is controversial, some authors reporting a significant association, others not, on the basis of the results of conventional virological diagnosis by culture or serology. This problem was reinvestigated in 88 patients using a semi-quantitative nest polymerase chain reaction (PCR) procedure for detecting CMV DNA in endomyocardial biopsy specimens. Significantly more positive biopsies were obtained from patients with moderate (grade 2; P = 0.02) or severe (grade 3a-4; P = 0.03) rejection than with no or mild (grade 0-1b) rejection, whereas there was no significant association between rejection and CMV as diagnosed by virus isolation from urine, throat or blood, or by the detection of CMV-IgM. PCR-positive biopsies originated most frequently from CMV-antibody positive recipients (R+) of hearts from seropositive donors (D+), in association with moderate or severe rejection rather than with mild or no rejection The detection of CMV in the heart thus seemed to be related more to R+D+ serological status than to severity of rejection, that is, to circumstances that favoured co-infection with strains of CMV from both donor and recipient. Studies on sequential biopsy specimens from selected patients also provided evidence that CMV infection and rejection were not always related events. The PCR was able to differentiate latent from active CMV infection; moreover, some seronegative individuals gave repeatedly positive biopsies, thereby supporting the work of others that some patients undergo CMV infection without mounting a detectable antibody response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗