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Biomedical subjects

J N Anderson

Publications and source records attributed to J N Anderson.

At least 19 recordsLinked to original sources
PubMed2003

Surfing, self-medicating and safety: buying non-prescription and complementary medicines via the internet.

OBJECTIVE: To examine whether the sale of medicines via the internet supports their safe and appropriate use. DESIGN: e-Pharmacy websites were identified using key words and a metasearch engine and the quality of information published on these websites was surveyed using the DISCERN tool. A case scenario and internet pharmacy practice standards were also used to evaluate the quality of care delivered. SETTING AND PARTICIPANTS: Between July and September 2001 104 websites were surveyed and 27 sent either Sudafed (pseudoephedrine HCl), St John's wort products, or both to a residential address in Melbourne, Australia. MAIN OUTCOME MEASURES: Quality of health information (DISCERN ratings), information exchanged between e-pharmacy staff and consumers, and product and delivery costs. RESULTS: Of 104 e-pharmacies from at least 13 different countries, 63 websites provided some health information but overall the quality of the information was poor. Only three website operators provided adequate advice to consumers to avoid a potential drug interaction. The costs for a daily dose of pseudoephedrine HCl (240 mg) ranged from 0.81 Australian dollars to 3.04 Australian dollars, and delivery costs from 3.28 Australian dollars to 62.70 Australian dollars. CONCLUSION: Consumers who self-select medicines from websites have insufficient access to information and advice at the point of ordering and on delivery to make informed decisions about their safe and appropriate use.

Adult↗
PubMed2001

Improving question formulation for use in evidence appraisal in a tertiary care setting: a randomised controlled trial [ISRCTN66375463].

BACKGROUND: The specificity of clinical questions is gauged by explicit descriptions of four dimensions: subjects, interventions, comparators and outcomes of interest. This study determined whether adding simple instructions and examples on clinical question formulation would increase the specificity of the submitted question compared to using a standard form without instructions and examples. METHODS: A randomised controlled trial was conducted in an evidence-search and appraisal service. New participants were invited to reformulate clinical queries. The Control Group was given no instructions. The Intervention Group was given a brief explanation of proper formulation, written instructions, and diagrammatic examples. The primary outcome was the change in the proportion of reformulated questions that described each the dimensions of specificity. RESULTS: Fifty-two subjects agreed to participate in the trial of which 13 were lost to follow-up. The remaining 17 Intervention Group and 22 Control Group participants were analysed. Baseline characteristics were comparable. Overall, 20% of initially submitted questions from both groups were properly specified (defined as an explicit statement describing all dimensions of specificity). On follow-up, 7/14 questions previously rated as mis-specified in the Intervention Group had all dimensions described at follow-up (p = 0.008) while the Control Group did not show any changes from baseline. Participants in the Intervention Group were also more likely to explicitly describe patients (p = 0.028), comparisons (p = 0.014), and outcomes (p = 0.008). CONCLUSIONS: This trial demonstrated the positive impact of specific instructions on the proportion of properly-specified clinical queries. The evaluation of the long-term impact of such changes is an area of continued research.

Allied Health Personnel↗
PubMed2001

Feasibility of an evidence-based literature search service for general practitioners.

OBJECTIVE: To test the feasibility of an evidence-based clinical literature search service to help answer general practitioners' (GPs') clinical questions. DESIGN: Two search services supplied GPs who submitted questions with the best available empirical evidence to answer these questions. The GPs provided feedback on the value of the service, and concordance of answers from the two search services was assessed. SETTING: Two literature search services (Queensland and Victoria), operating for nine months from February 1999. MAIN OUTCOME MEASURES: Use of the service; time taken to locate answers; availability of evidence; value of the service to GPs; and consistency of answers from the two services. RESULTS: 58 GPs asked 160 questions (29 asked one, 11 asked five or more). The questions concerned treatment (65%), aetiology (17%), prognosis (13%), and diagnosis (5%). Answering a question took a mean of 3 hours 32 minutes of personnel time (95% CI, 2.67-3.97); nine questions took longer than 10 hours each to answer, the longest taking 23 hours 30 minutes. Evidence of suitable quality to provide a sound answer was available for 126 (79%) questions. Feedback data for 84 (53%) questions, provided by 42 GPs, showed that they appreciated the service, and asking the questions changed clinical care. There were many minor differences between the answers from the two centres, and substantial differences in the evidence found for 4/14 questions. However, conclusions reached were largely similar, with no or only minor differences for all questions. CONCLUSIONS: It is feasible to provide a literature search service, but further assessment is needed to establish its cost effectiveness.

Attitude of Health Personnel↗
PubMed2001

Estimates of complications of medical care in the adult US population.

BACKGROUND: Total US population estimates of complications of medical care have relied on extrapolations of state-specific estimates. Generalizability is suspect because findings are limited by geographical location or time. We describe the relationship between the annual prevalence of complications of medical care (CM) and socio-demographic characteristics in the adult US population. METHODS: We used data from the National Health Interview Surveys, annual nationwide surveys of the resident, civilian, noninstitutionalized population of the United States. The main outcome of interest was self-reported conditions from CMs (ICD-9 996-999) and activity limitations that arise from such events. Univariate estimates and multivariably adjusted models accounting for selected socio-demographic characteristics and health status were derived. RESULTS: A total of 618,167 reports of conditions from 313,438 subjects 18 years and older from 1987 to 1994 were examined. In 1987, 830,386 adults reported complications of medical care, increasing by about 40% to 1,174,089 adults in 1994. Based on an extrapolation to the US adult population, rates increased by 25% from 558 to 678 per 100,000 during the same period. One-third reported onset a year prior to the interview; two-thirds visited a doctor six months prior; half experienced limitation in major activities; a quarter reported limitation in personal care activities. In the two weeks preceding the interview, complications of medical care caused an average of 1.72 days of restricted activity, 0.79 days spent in bed, and 0.58 days of work lost. Race modified the age-specific risk of these complications. CONCLUSIONS: Complications of medical care impose heavier morbidity than previously considered with some indication that socio-demographic variables modify the risk for injuries.

Activities of Daily Living↗
PubMed2001

Exploitation of the low fidelity of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and the nucleotide composition bias in the HIV-1 genome to alter the drug resistance development of HIV.

The RNA genome of the lentivirus human immunodeficiency virus type 1 (HIV-1) is significantly richer in adenine nucleotides than the statistically equal distribution of the four different nucleotides that is expected. This compositional bias may be due to the guanine-to-adenine (G-->A) nucleotide hypermutation of the HIV genome, which has been explained by dCTP pool imbalances during reverse transcription. The adenine nucleotide bias together with the poor fidelity of HIV-1 reverse transcriptase markedly enhances the genetic variation of HIV and may be responsible for the rapid emergence of drug-resistant HIV-1 strains. We have now attempted to counteract the normal mutational pattern of HIV-1 in response to anti-HIV-1 drugs by altering the endogenous deoxynucleoside triphosphate pool ratios with antimetabolites in virus-infected cell cultures. We showed that administration of these antimetabolic compounds resulted in an altered drug resistance pattern due to the reversal of the predominant mutational flow of HIV (G-->A) to an adenine-to-guanine (A-->G) nucleotide pattern in the intact HIV-1-infected lymphocyte cultures. Forcing the virus to change its inherent nucleotide bias may lead to better control of viral drug resistance development.

Anti-HIV Agents↗
PubMed1999

DNA distortion as a factor in nucleosome positioning.

In a previous report we constructed a synthetic DNA sequence that directed the deposition of histone octamers to a single site, and it was proposed that DNA distortion was involved in the positioning effect. In the present study we utilized the chemical probe potassium permanganate to identify sites of DNA distortion in the synthetic positioning sequence. A permanganate hypersite was identified 15 bp from the nucleosome pseudo-dyad at a site known to display DNA distortion in the mature nucleosome. The sequence of the site contained a TA step flanked by an oligo-pyrimidine tract. A series of substitutions were made in the region of the permanganate hypersite and the resulting constructs tested for affinity for histone octamers and translational positioning in in vitro studies. The results revealed that either a single base substitution at the TA step or in the adjacent homopolymeric tract dramatically affected affinity and positioning activity. The rotational orientation of the permanganate-sensitive sequence was shown to be important for functions, since altering the orientation of the site in a positioning fragment reduced positioning activity and octamer affinity, while altering the rotational orientation of the sequence in a non-positioning fragment had the opposite effects. A reconstituted 5 S rDNA positioning sequence from Lytechinus variegatus was also shown to display a permanganate hypersite 16 bp from its pseudo-dyad.

Animals↗
PubMed1999

Selective nucleosome disruption by drugs that bind in the minor groove of DNA.

Previous studies have shown that drugs which bind in the DNA minor groove reduce the curvature of bent DNA. In this article, we examined the effects of these drugs on the nucleosome assembly of DNA molecules that display different degrees of intrinsic curvature. DAPI (4,6-diamidino-2-phenylindole) inhibited the assembly of a histone octamer onto a 192-base pair circular DNA fragment from Caenorhabditis elegans and destabilized a nucleosome that was previously assembled on this segment. The inhibitory effect was highly selective since it was not seen with nonbent molecules, bent molecules with noncircular shapes, or total genomic DNA. This marked template specificity was attributed to the binding of the ligand to multiple oligo A-tracts distributed over the length of the fragment. A likely mechanism for the effect is that the bound ligand prevents the further compression of the DNA into the minor groove which is required for assembly of DNA into nucleosomes. To further characterize the effects of the drug on chromatin formation, a nucleosome was assembled onto a 322-base pair DNA fragment that contained the circular element and a flanking nonbent segment of DNA. The position of the nucleosome along the fragment was then determined using a variety of nuclease probes including exonuclease III, micrococcal nuclease, DNase I, and restriction enzymes. The results of these studies revealed that the nucleosome was preferentially positioned along the circular element in the absence of DAPI but assembled onto the nonbent flanking sequence in the presence of the drug. DAPI also induced the directional movement of the nucleosome from the circular element onto the nonbent flanking sequence when a nucleosome preassembled onto this template was exposed to the drug under physiologically relevant conditions.

Animals↗
PubMed1999

Heterogeneity in the actions of drugs that bind in the DNA minor groove.

Distamycin and Hoechst 33258 have long served as the model compounds for biochemical, biophysical, and clinical studies of the drugs that bind in the DNA minor groove. However, the results presented in this investigation clearly show that 4,6-diamidino-2 phenylindole (DAPI) is superior to both of these drugs at negating the effects of intrinsic DNA curvature and anisotropic bendability as measured by electrophoretic and ligation analysis. In addition, DAPI was more effective than distamycin and Hoechst 33258 at inhibiting the assembly of nucleosomes onto synthetic and natural sequences that have multiple closely spaced oligo-AT sequences that serve as drug binding sites. Since these effects may be related to the biological action of the drugs, it was of interest to determine the mechanism that was responsible for the enhanced action of DAPI. The possibility that the differential drug potencies resulted from differential overall affinities of the ligands for A-tract molecules was considered, but drug binding studies suggested that this was not the case. It is also unlikely that the differential drug effects resulted from the binding of the drugs to different DNA sites since the oligo A/T binding sites for DAPI and Hoechst were centered on the same nucleotide positions as revealed by footprinting studies using exonuclease III, DNase I, and hydroxyl radical. However, the footprinting studies with DNase I did uncover a potentially important difference between the drugs. DAPI protected only the AT bp in the binding sites, while distamycin and Hoechst protected these bp as well as flanking Gs and Cs. These results permitted us to advance a preliminary model for the enhanced action DAPI. According to the model, the short length of DAPI and its absolute specificity for A/T bps with narrow minor grooves ensures that only particularly minor grooves that give rise to curvature and anisotropic bendability are occupied by the drug. Consequently, each helical deflection induced by an A-tract in the absence of the drug is countered by an opposite deflection induced by DAPI binding, thus effectively neutralizing intrinsic curvature and bending into the minor groove.

Animals↗
PubMed1999

Preference for thinness in Singapore--a newly industrialised society.

BACKGROUND/AIMS: A cultural preference for thinness has been implicated in the development of eating disorders in Western, post-industrialised societies. In transitional societies like Singapore, a shift in expectations of ideal body size (toward thinness) may lead to an increase in eating disorders. This study investigated perceptions about body size and shape in over 200 youths living in Singapore, and the influences of adiposity, gender, Westernization and parents' education. METHODS: A self-administered questionnaire was used to gather social and cultural information from 137 males and 143 females, aged 17-22 years. It included questions relating to eating behaviour and body satisfaction from which a "preference for thinness score" was derived. Westernization was indicated by language spoken at home. Adiposity was measured by triceps skinfold and body mass index. Multiple linear regression analysis was used to assess the associations of adiposity, mother's education, father's education, and language spoken at home with the preference for thinness score. RESULTS: Dissatisfaction with body size and shape increased with tertile of adiposity among females, and thoughts about dieting and becoming thinner were present even among underweight girls. Unlike the females, the highest proportion of males satisfied with their body size and shape, was associated with the middle tertile of BMI. Speaking English at home, but not parents' education, was positively associated with body dissatisfaction after controlling for BMI. CONCLUSION: Chinese Singaporean female youths have a preference for thinness as an ideal body size. The epidemiology of eating disorders in Singapore and other newly industrialised societies warrants further investigation.

Adolescent↗
PubMed1998

Unique translational positioning of nucleosomes on synthetic DNAs.

A computational study was previously carried out to analyze DNA sequences that are known to position histone octamers at single translational sites. A conserved pattern of intrinsic DNA curvature was uncovered that was proposed to direct the formation of nucleosomes to unique positions. The pattern consists of two regions of curved DNA separated by preferred lengths of non-curved DNA. In the present study, 11 synthetic DNAs were constructed which contain two regions of curved DNA of the form [(A5.T5)(G/C)5]4 separated by non-curved regions of variable length. Translational mapping experiments of in vitro reconstituted mononucleosomes using exonuclease III, micrococcal nuclease and restriction enzymes demonstrated that two of the fragments positioned nucleosomes at a single site while the remaining fragments positioned octamers at multiple sites spaced at 10 base intervals. The synthetic molecules that positioned nucleosomes at a single site contain non-curved central regions of the same lengths that were seen in natural nucleosome positioning sequences. Hydroxyl radical and DNase I digests of the synthetic DNAs in reconstituted nucleosomes showed that the synthetic curved element on one side of the nucleosomal dyad assumed a rotational orientation where narrow minor grooves of the A-tracts faced the histone surface with all molecules. In contrast, the curved element on the other side of the nucleosome displayed variable rotational orientations between molecules which appeared to be related to the positioning effect. These results suggest that asymmetry between the two halves of nucleosomal DNA may facilitate translational positioning.

Base Sequence↗