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Biomedical subjects

C Aitken

Publications and source records attributed to C Aitken.

At least 19 recordsLinked to original sources

Conceptual development of an information systems framework for improving continuity in epidemiological research.

Lack of continuity is a problem for survey-based epidemiological research. Poor access to experience and inadequate retention of information means new projects seldom build on successful predecessors to the maximum possible extent. We have designed a data management framework which addresses this problem using a well-known information systems approach. Our ideas provide a means of storing data in a manner which reflects the original research concepts. This makes collected data accessible and understandable without reference to the questionnaire, and allows new questionnaires to be designed quickly and easily. Our framework provides a means for recording developmental, conceptual and other supporting information and documentation which is traditionally poorly conserved. We illustrate the components of the framework using a major Australian epidemiological project as a case study. Once the necessary software is developed, our framework will improve organisational memory within individual research units and has the potential to become a valuable support tool for survey-based research.

Australia

Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults.

We performed a cross-sectional study (n = 49 males, 57 females) and a randomized double-blind placebo-controlled dietary intervention study (n = 31/32 per group) to determine the effect of folate and vitamin B12 (B12) on DNA damage (micronucleus formation and DNA methylation) and plasma homocysteine (HC) in young Australian adults aged 18-32 years. None of the volunteers were folate deficient (i.e. red blood cell folate <136 nmol/l) and only 4.4% (all females) were vitamin B12 deficient (i.e. serum vitamin B12 <150 pmol/l). The cross-sectional study showed that (i) the frequency of micronucleated cells (MNCs) was positively correlated with plasma HC in males (R = 0.293, P < 0.05) and (ii) in females MNC frequency was negatively correlated with serum vitamin B12 (R = -0.359, P < 0.01) but (iii) there was no significant correlation between micronucleus index and folate status. The results also showed that the level of unmethylated CpG (DNA) was not significantly related to vitamin B12 or folate status. The dietary intervention involved supplementation with 3.5x the recommended dietary intake (RDI) of folate and vitamin B12 in wheat bran cereal for three months followed by ten times the RDI of these vitamins via tablets for a further three months. In the supplemented group, MNC frequency was significantly reduced during the intervention by 25.4% in those subjects with initial MNC frequency in the high 50th percentile but there was no change in those subjects in the low 50th percentile for initial MNC frequency. The reduction in MNC frequency was significantly correlated with serum vitamin B12 (R = -0.49, P < 0.0005) and plasma HC (R = 0.39, P < 0.006), but was not significantly related to red blood cell folate. DNA methylation status was not altered in the supplemented group. The greatest decrease in plasma HC (by 37%) during the intervention was observed in those subjects in the supplemented group with initial plasma HC in the high 50th percentile, and correlated significantly with increases in red blood cell folate (R = -0.64, P < 0.0001) but not with serum vitamin B12. The results from this study suggest that (i) MNC frequency is minimized when plasma HC is below 7.5 micromol/l and serum vitamin B12 is above 300 pmol/l and (ii) dietary supplement intake of 700 microg folic acid and 7 microg vitamin B12 is sufficient to minimize MNC frequency and plasma HC. Thus, it appears that elevated plasma HC, a risk factor for cardiovascular disease, may also be a risk factor for chromosome damage.

Adult

Evaluation of the murex hybrid capture cytomegalovirus DNA assay versus plasma PCR and shell vial assay for diagnosis of human cytomegalovirus viremia in immunocompromised patients.

We evaluated a cytomegalovirus (CMV) 24-hour shell vial assay (SVA), the Murex Hybrid Capture CMV DNA assay (HCA), and a CMV plasma PCR for the detection of CMV viremia in renal and bone marrow transplant recipients and human immunodeficiency virus-infected patients. CMV viremia was detected by at least one method in 125 of 317 evaluable samples (39.4%) from 78 patients and was detected in 19.8% of samples by SVA, 26.8% by HCA, and 32.2% by plasma PCR. There was moderate to substantial agreement between the results of the different tests (kappa coefficient = 0.415 to 0.631). However, HCA and plasma PCR were significantly more sensitive than SVA (P = 0.001 and P < 0.0001, respectively; McNemar's test), and plasma PCR was more sensitive than HCA (P = 0.031; McNemar's test). HCA and plasma PCR were more consistently positive than SVA during viremic episodes (P = 0.0002 and P < 0.0001, respectively; McNemar's test). The use of HCA or plasma PCR may therefore improve the diagnosis and management of CMV disease in susceptible patient groups.

AIDS-Related Opportunistic Infections

Vitamin-E supplements and their effect on vitamin-E status in blood and genetic damage rate in peripheral blood lymphocytes.

A placebo-controlled double-blind intervention trial was performed using 60 male volunteers aged between 50 and 70 years to test the hypothesis that intake of d-alpha-tocopherol (VITE) above the recommended dietary intake (RDI) level (10.0 mg or 14.9 IU VITE) can protect against DNA damage in human peripheral blood lymphocytes. The intervention consisted of two phases, each of 8 weeks duration: during the initial phase the VITE supplement was 5 x RDI (provided in cereal) and during the second phase the VITE supplement was 30 x RDI (provided in capsules). Blood samples were collected before the initial phase, between phases and at the end of the second phase; the level of VITE was measured in plasma using HPLC and genetic damage rate in peripheral blood lymphocytes was measured using the cytokinesis-block micronucleus assay. The study has shown that cereal supplementation is an effective route for an above RDI intake of VITE; a 5 x RDI supplement resulted in a 22% elevation in the plasma VITE status. By comparison the use of 30 x RDI supplementation with capsules as the route of delivery resulted in an 89% increment in plasma VITE status. The increased VITE status during the intervention, however, had no significant impact on the spontaneous genetic damage rate in human lymphocytes. There was also no correlation between baseline genetic damage frequency and VITE status. However, a 32% (P < 0.007) decrease in the micronucleus index was recorded in both the control and VITE-supplemented groups during the course of the study which could have been due either to seasonal effects or other common components in the diet such as the carrier used for the VITE in the cereal and the capsules. The study has identified a small proportion (3.4%) of apparently healthy individuals who are abnormally sensitive to oxidative stress by hydrogen peroxide and demonstrated that VITE supplementation did not attenuate the impact of the oxidative challenge on genetic damage rate. The above data suggest that supplements in cereal are a viable route for delivering VITE and that supplementation with VITE is unlikely to affect chromosome damage occurring spontaneously or as a result of exposure to oxidative radicals.

Aged

Moderate wine consumption protects against hydrogen peroxide-induced DNA damage.

We have tested the hypothesis that moderate wine drinking can protect somatic cells against the DNA-damaging effect of hydrogen peroxide which is an endogenous source of reactive oxygen metabolites. In this preliminary investigation, four male volunteers were placed on a plant-polyphenol-free (PPF) diet to ensure that the wine provided was the only main source of plant phenolic compounds. After 48 h on the PPF diet the volunteers were required to consume 300 ml of red or white wine and blood samples collected 1, 3, 8 and 24 h post-consumption while still on a PPF diet. Plasma was isolated from the blood samples and stored frozen for subsequent assays. In the subsequent assays, fresh lymphocytes from each donor were incubated in their corresponding plasma from the various intervention time-points for 30 min. The capacity of the plasma to prevent damage to DNA in lymphocytes by hydrogen peroxide was assessed using the cytokinesis-block micronucleus technique. The data from this preliminary investigation indicated that there was a strong inhibition (>70%) of hydrogen peroxide-induced micronucleated cells by the plasma samples from the blood collected 1 h after consumption of wine as compared to plasma samples from blood immediately before the consumption of wine. This protective effect was apparent for both red and white wine although statistical significance (P = 0.0068) was achieved only in the white wine intervention. A higher degree of statistical significance (P = 0.0008) was achieved when the data for samples following the consumption of red and white wine were combined. There was no difference in the hydrogen-peroxide-induced micronucleated cell frequency when comparing results immediately before starting on the PPF diet, before consumption of wine, 8 h after or 24 h after wine consumption. The hydrogen peroxide-induced micronucleated cell frequency in cells incubated with plasma from blood collected 3 h after wine consumption was intermediate to that observed for plasma after 1 and 8 h after wine intake. The protective effect of plasma against DNA damage cannot be readily explained by the red wine content of phenolic compounds because results for red wine were similar to those for white wine even though white wine had a much lower level of total polyphenols. A possible explanation could be that alcohol, glycerol and ascorbate in wine together with specific wine phenolic compounds that are also equally present in red and white wine (e.g. hydroxycinnamates) may have contributed to the observed protection of nuclear material from hydrogen peroxide-derived reactive oxygen metabolites. This explanation is supported by data from in vitro experiments showing that incubation of lymphocytes either with alcohol or wine stripped of phenolic compounds resulted in a statistically significant (P < 0.05) dose-related reduction (up to 87% reduction) in hydrogen peroxide-induced micronucleated cell frequency.

Adult

Is HTLV-1 status another antenatal screening test that we need?

Human T-lymphocytic virus type 1 (HTLV-1) carriage is associated with a 2% to 5% lifetime risk of developing a severe, if not fatal, disease. In our Inner London antenatal population, we found that the carrier rate was 0.3%. The antenatal transmission rate is known to be very low, but if the infant is breastfed the transmission rate is up to 25%. It is therefore possible to interrupt the transmission cycle by advising against breastfeeding. The ethical and fiscal issues surrounding antenatal testing are addressed.

Enzyme-Linked Immunosorbent Assay

Molecular epidemiology and significance of a cluster of cases of CMV infection occurring on a special care baby unit.

Sequencing of the amino-terminal region of the glycoprotein H gene was used to investigate the possibility of a common source for cytomegalovirus (CMV) infection occurring in five premature babies. All but two of the strains were different, indicating that this cluster of infection occurring on the special care baby unit was unlikely to be epidemiologically linked.

Cross Infection

Comparative efficacy of oral doses of clindamycin and erythromycin in the prevention of bacteraemia.

Two antibiotics, clindamycin and erythromycin, were compared in a double-blind trial to test their efficacy in the prevention of post-dental extraction bacteraemia with streptococci in a group of 40 healthy patients. Tolerance to the oral doses was tested by questionnaire. Levels of drug in the serum were estimated using a microbiological assay. An in-vitro blood culture system was used as an analogy of the persistence of a bacteraemia in the presence of high levels of antibiotic. Isolates of streptococci were identified to species level. Minimum inhibitory concentrations of clindamycin and of erythromycin for each isolate were estimated. Results showed satisfactory levels of antibiotics in the blood for activity against oral streptococci. Clindamycin was slightly more effective than erythromycin in the prevention of post-extraction streptococcal bacteraemia but that efficacy was only 45%. Clindamycin as a single oral dose of 600 mg was well tolerated by patients compared with erythromycin 1.5 g.

Abdominal Pain

Diagnosing respiratory syncytial virus by nasal lavage.

Nasal lavage was compared with nasopharyngeal aspiration for diagnosis of respiratory syncytial virus infection. Nasal lavage and nasopharyngeal aspiration were performed on 50 occasions in 32 infants (median age 5.6 months) with acute viral wheezing. Compared with nasopharyngeal aspiration, nasal lavage had a positive predictive value of 95.6% and negative predictive value of 92.5%. These comparable results and lack of adverse effects make nasal lavage the preferred method.

Child, Preschool

Heterogeneity within the Epstein-Barr virus nuclear antigen 2 gene in different strains of Epstein-Barr virus.

DNA isolated from biopsies of endemic Burkitt's lymphoma (BL) from New Guinea was analysed for the presence of Epstein-Barr virus (EBV) sequences using the polymerase chain reaction. Primers were designed to amplify sequences within the Epstein-Barr virus nuclear antigen (EBNA) 1 and 2 genes. These analyses detected the EBNA1 sequence in all the biopsies studied. Additional sets of primers directed against the EBNA2 gene were used in order to categorize the EBV strains as A-type or B-type (39% A-type; 50% B-type; 5% A- and B-type; 5% untypeable). These results indicated that DNA sequence heterogeneity within the EBNA2 gene region may exist in different strains of EBV. The extent of DNA sequence heterogeneity among different strains of EBV was determined by sequencing of a region within the EBNA2 gene in a number of different A-type and B-type strains of EBV originating from Africa or New Guinea. The results demonstrated DNA sequence heterogeneity within the EBNA2 gene in different strains of EBV. This heterogeneity was more extensive among A-type strains than B-type strains of EBV.

Africa

Attitudes and prognosis in chronic low back pain.

Eighteen patients with chronic low back pain were interviewed before and after a programme of conservative treatment and again 4 months later. Measures were made of severity and attitude towards disability, including the Kelly Repertory Grid. The best predictor of improvement was the degree of meaningfulness of the concept 'self in pain' as measured by the Repertory Grid.

Activities of Daily Living

Psychosomatics for all--past, present and future.

It used to be fashionable to begin consideration of psychosomatics about philosophy of mind and body. Nowadays it is a topic about health and practical care of patients--principally about the psychological aspects of any illness. Pathogenesis is becoming understood with some risk factors clearly identifiable. The high incidence of symptoms attributable to emotional disturbance has now been described in so many conditions that it is altering the delivery of health services. The boundaries of psychosomatics are extending. No longer is the topic confined to a few chronic diseases, even including new ones like AIDS, but it now includes support for carers and education about behaviour for health, to name two currently important aspects. The responsibility for the biopsychosocial approach does not lie alone with doctors, and certainly not only psychiatrists, but the many professionals involved in clinical care. The aim is not simply reducing symptoms, but improving functional capabilities and preventing social disadvantage. The more the advance of knowledge, the more intriguing become the questions awaiting answers. The risk factors due to predisposition or unhealthy behaviour and stress still only account for a small contribution to aetiology. Coping mechanisms, whether in personality or social support, still defy enough understanding to predict which patients will develop emotional disturbance, and which patients will respond to appropriate treatment. Perhaps, the most intriguing question is why, when certain relevant facts about unhealthy behaviour are beyond dispute, such as the effect of drinking excessive alcohol, smoking nicotine, having unsafe sex, poor family caring or receiving insensitive treatment, it remains so difficult to bring about improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Psychological

Care of disabled people in the community.

The initiatives raised by the International Year of Disabled Persons led to an understanding that the community may well be the best place to help disabled people. It is important to ensure that any major switch of resources from institutional to community care should be properly appraised, not just on cost-effectiveness grounds but also on the needs of the disabled persons themselves. Apart from the traditional medical input there is an imperative need to involve other professional and informal helpers to ensure the best possible outcome.

Community Health Services