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Biomedical subjects

John Dunn

Publications and source records attributed to John Dunn.

18 recordsLinked to original sources
PubMed2006

Immunogenicity and reactogenicity of 1 versus 2 doses of trivalent inactivated influenza vaccine in vaccine-naive 5-8-year-old children.

BACKGROUND: Two doses of trivalent inactivated influenza vaccine (TIV) are recommended for children <9 years old receiving vaccine for the first time, but compliance is suboptimal. This study assessed the need for a second dose of TIV in this age group. METHODS: In this prospective, open-label study, 232 influenza vaccine-naive 5-8-year-olds enrolled in a health maintenance organization received 2 doses of TIV in fall 2004. Serum for antibody titer measurement was obtained at 3 time points (n = 222). Parents completed diaries for 5 days. RESULTS: Both doses of vaccine were well tolerated. The strongest predictor of a protective antibody response (> or =1 : 40) after 1 dose of TIV was baseline seropositive status. In multivariate analysis adjusting for age, sex, and baseline serostatus, the proportion of children with protective antibody responses was significantly higher after 2 doses than after 1 dose of TIV for each antigen (P < .001, for A/H1N1; P = .01, for A/H3N2; P < .001, for B). Age and sex were not independently predictive of a protective antibody response. Over one-third of children had antibody responses <1:40 for the type B vaccine component, even after 2 doses. CONCLUSIONS: The present study supports the need for 2 doses of TIV in 5-8-year-olds receiving TIV for the first time. Efforts to increase compliance with the 2-dose recommendation are warranted.

Antibodies, Viral↗
PubMed2006

Genomic environment predicts expression patterns on the human inactive X chromosome.

What genomic landmarks render most genes silent while leaving others expressed on the inactive X chromosome in mammalian females? To date, signals determining expression status of genes on the inactive X remain enigmatic despite the availability of complete genomic sequences. Long interspersed repeats (L1s), particularly abundant on the X, are hypothesized to spread the inactivation signal and are enriched in the vicinity of inactive genes. However, both L1s and inactive genes are also more prevalent in ancient evolutionary strata. Did L1s accumulate there because of their role in inactivation or simply because they spent more time on the rarely recombining X? Here we utilize an experimentally derived inactivation profile of the entire human X chromosome to uncover sequences important for its inactivation, and to predict expression status of individual genes. Focusing on Xp22, where both inactive and active genes reside within evolutionarily young strata, we compare neighborhoods of genes with different inactivation states to identify enriched oligomers. Occurrences of such oligomers are then used as features to train a linear discriminant analysis classifier. Remarkably, expression status is correctly predicted for 84% and 91% of active and inactive genes, respectively, on the entire X, suggesting that oligomers enriched in Xp22 capture most of the genomic signal determining inactivation. To our surprise, the majority of oligomers associated with inactivated genes fall within L1 elements, even though L1 frequency in Xp22 is low. Moreover, these oligomers are enriched in parts of L1 sequences that are usually underrepresented in the genome. Thus, our results strongly support the role of L1s in X inactivation, yet indicate that a chromatin microenvironment composed of multiple genomic sequence elements determines expression status of X chromosome genes.

Algorithms↗
PubMed2006

Use of single-point genome signature tags as a universal tagging method for microbial genome surveys.

We developed single-point genome signature tags (SP-GSTs), a generally applicable, high-throughput sequencing-based method that targets specific genes to generate identifier tags from well-defined points in a genome. The technique yields identifier tags that can distinguish between closely related bacterial strains and allow for the identification of microbial community members. SP-GSTs are determined by three parameters: (i) the primer designed to recognize a conserved gene sequence, (ii) the anchoring enzyme recognition sequence, and (iii) the type IIS restriction enzyme which defines the tag length. We evaluated the SP-GST method in silico for bacterial identification using the genes rpoC, uvrB, and recA and the 16S rRNA gene. The best distinguishing tags were obtained with the restriction enzyme Csp6I upstream of the 16S rRNA gene, which discriminated all organisms in our data set to at least the genus level and most organisms to the species level. The method was successfully used to generate Csp6I-based tags upstream of the 16S rRNA gene and allowed us to discriminate between closely related strains of Bacillus cereus and Bacillus anthracis. This concept was further used successfully to identify the individual members of a defined microbial community.

Bacillus anthracis↗
PubMed2006

Prophylaxis with acetaminophen or ibuprofen for prevention of local reactions to the fifth diphtheria-tetanus toxoids-acellular pertussis vaccination: a randomized, controlled trial.

BACKGROUND: The frequency of local vaccination reactions increases with successive doses of diphtheria-tetanus toxoids-acellular pertussis (DTaP) vaccine, and local reactions occur for the majority of children receiving the fifth DTaP vaccination. It is not known whether these reactions can be prevented with prophylactic use of acetaminophen or ibuprofen. METHODS: In this 3-group, randomized, blinded, controlled trial, 372 children were assigned randomly, in a 2:2:1 ratio, to receive 3 doses of acetaminophen, ibuprofen, or placebo. The first dose of study medication was administered within 2 hours before the fifth DTaP vaccination, and the remaining 2 doses were given at 6-hour intervals. The primary outcome measures included a local reaction with an area of redness or discoloration > or =5 cm in diameter on the evening of or during the 2 days after vaccination, an increase in mid-limb circumference of > or =2 cm on the evening of or during the 2 days after vaccination, and a persistent local reaction, defined as an area of redness or discoloration present on the third day after vaccination. RESULTS: Local reactions with a > or =5-cm area of redness or discoloration were reported for 35% of children in the placebo group, compared with 33% of children in the acetaminophen group and 37% of children in the ibuprofen group. There was also no significant difference between the placebo and treatment groups in the proportions of children with a > or =2-cm increase in mid-limb circumference or with a persistent local reaction. CONCLUSIONS: We did not find evidence that prophylaxis with acetaminophen or ibuprofen offers a clinically significant benefit in prevention of local reactions to the fifth DTaP vaccination.

Acetaminophen↗
PubMed2006

Causes of death among crack cocaine users.

OBJECTIVE: The study accompanied 131 crack-cocaine users over a 5-year period, and examined mortality patterns, as well as the causes of death among them. METHOD: All patients admitted to a detoxification unit in Sao Paulo between 1992 and 1994 were interviewed during two follow-up periods: 1995-1996 and 1998-1999. RESULTS: After 5 years, 124 patients were localized (95%). By the study endpoint (1999), 23 patients (17.6%) had died. Homicide was the most prevalent cause of death (n = 13). Almost one third of the deaths were due to the HIV infection, especially among those with a history of intravenous drug use. Less than 10% died from overdose. CONCLUSIONS: The study suggests that the mortality risk among crack cocaine users is greater than that seen in the general population, homicide and AIDS being the most common causes of death among such individuals.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Motivation to change drinking behavior: the differences between alcohol users from an outpatient gastroenterology clinic and a specialist alcohol treatment service.

CONTEXT AND OBJECTIVE: For some patients who have developed significant alcohol-related physical disease, total abstinence from alcohol may offer the best chance of survival. The aim of this study was to investigate motivation for treatment in two groups of alcohol users: outpatients from the gastroenterology clinic and outpatients from the specialist alcohol treatment service. DESIGN AND SETTING: Cross-sectional study, at a federally funded public teaching hospital. METHODS: The sample studied was 151 outpatients from the gastroenterology clinic and 175 from the specialist alcohol treatment service. The interview was conducted in the outpatient clinics at the first appointment, and consisted of demographic questions and scales for measuring quality of life, alcohol dependence, pattern of alcohol, motivation for treatment and consequences of alcohol consumption. RESULTS: The results suggested that outpatients from the gastroenterology clinic were less dependent on alcohol, had suffered fewer consequences from alcohol and had fewer emotional and mental health problems than did the outpatients from the alcohol treatment service. In relation to their stages of change, the gastroenterology outpatients presented high precontemplation scores at the beginning of treatment while outpatients of alcohol treatment service showed higher scores in contemplation, action and maintenance. CONCLUSION: The medical treatment may be a reason for the temporary alcohol abstinence behavior among the gastroenterology outpatients.

Adult↗
PubMed2004

[Factor structure of the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) in alcohol dependent outpatients].

OBJECTIVE: The aim of this study was to investigate the reliability and factor structure of the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES), version 8, a 19-item self-reported instrument developed to measure readiness to change in alcohol-dependent alcoholics. METHODS: A Confirmatory Factor analysis of the SOCRATES was performed based on the factor structures previously demonstrated by Miller & Tonigan and Maisto et al. in a sample with 326 alcohol-dependent outpatients. The questionnaire was translated into Portuguese, cross-culturally adapted and back-translated into English. During this process SOCRATES underwent some modifications to simplify some complex question formats. RESULTS: The analysis showed that two correlated factors provided the best fit for the data and that these were similar to Maisto et al.'s factors. CONCLUSIONS: There was less evidence to support a three-factor structure. The results are compared to previous studies and the reasons for discrepancies are discussed.

Alcohol Drinking↗
PubMed2004

High-throughput liquid chromatography-tandem mass spectrometry determination of bupropion and its metabolites in human, mouse and rat plasma using a monolithic column.

In the present work, a high-throughput LC/MS/MS method using a Chromolith RP-18 (50 mm x 4.6 mm) monolithic column was developed and partially validated for the determination of bupropion (BUP), an anti-depressant drug, and its metabolites, hydroxybupropion and threo-hydrobupropion (TB), in human, mouse, and rat plasma. A modern integrated liquid chromatograph and an LC/MS/MS system with a TurboIonSpray (TIS) interface were used for the positive electrospray selected reaction monitoring (SRM) LC/MS analyses. Spiked control plasma calibration standards and quality control (QC) samples were extracted by semi-automated 96-well liquid-liquid extraction (LLE) using ethyl acetate. A mobile phase consisting of 8mM ammonium acetate-acetonitrile (55:45, v/v) delivered isocratically at 5 ml/min, and split post-column to 2 ml/min directed to the TIS, provided the optimum conditions for the chromatographic separation of bupropion and its metabolites within 23s. The isotope-labeled D(6)-bupropion and D(6)-hydroxybupropion were used as internal standards. The method was linear over a concentration range of 0.25-200 ng/ml (bupropion and threo-hydrobupropion), and 1.25-1000 ng/ml (hydroxybupropion). The intra- and inter-day assay accuracy and precision were within 15% for all analytes in each of the biological matrices. The monolithic column performance as a function of column backpressure, peak asymmetry, and retention time reproducibility was adequately maintained over 864 extracted plasma injections.

Animals↗
PubMed2004

Outer surface lipoproteins of Borrelia burgdorferi vary in their ability to induce experimental joint injury.

OBJECTIVE: To examine the ability of bacterial lipoproteins from the spirochete Borrelia burgdorferi to cause in vivo tissue injury (arthritis). METHODS: Outer surface proteins (OSPs) from B burgdorferi were used in a rat model of antigen-induced allergic arthritis. Intraarticular challenge with recombinant OspA, OspB, and OspC in nonlipidated (peptide) and lipidated forms was performed in the left knee joint; the contralateral joint received buffer as control. Inflammation was monitored by technetium scintigraphy and histology. RESULTS: Nonlipidated (peptide) OspA, OspB, and OspC did not induce arthritis; the only exception was polymerized OspA, which was tested in preimmunized rats. Lipidated OspA from 2 different strains and lipidated OspC induced severe arthritis, whereas lipidated OspB failed to induce injury. A synthetic analog of the OSP lipid modification, lipopeptide Pam(3)Cys-Ser-Lys(4)-OH, either alone or coupled to bovine serum albumin, also failed to induce injury. Injury did not develop in control groups that were given the appropriate buffers or lipopolysaccharide. This showed that lipidated borrelial OSPs can be potent arthritogens but vary greatly with respect to their injury-inducing potential. The possession of a lipid modification is essential but is not sufficient to render an OSP arthritogenic. CONCLUSION: This is the first study to demonstrate that individual lipoproteins from B burgdorferi can induce experimental joint injury in vivo. These results may help elucidate the pathogenesis of Lyme arthritis and, above all, underline the importance of bacterial lipoproteins as major virulence factors.

Animals↗
PubMed2004

Increasing throughput of parallel on-line extraction liquid chromatography/electrospray ionization tandem mass spectrometry system for GLP quantitative bioanalysis in drug development.

An approach is described with turbulent flow on-line extraction liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for GLP quantitative bioanalysis of a drug candidate. Two systems were built in-house with standard laboratory parts and equipments. One system consisted of one gradient HPLC pump, one isocratic pump, one ten-port valve, two turbulent flow columns, one analytical column, one autosampler and one mass spectrometer. Using this system, an injection-to-injection cycle time of 0.8 min was achieved. By adding an additional valve, another analytical column and an isocratic pump, the injection-to-injection cycle time decreased to 0.4 min. Validation results from the two systems showed that precision and accuracy were acceptable for GLP quantitative analyses. The system was utilized to support sample bioanalysis of a drug candidate in a first-time in-human clinical trial.

Animals↗
PubMed2004

Factors associated with adverse reactions to cocaine among a sample of long-term, high-dose users in São Paulo, Brazil.

This cross-sectional survey investigates the frequency of adverse cocaine reactions and associated factors among regular cocaine misusers. A sample of 332 cocaine misusers from a range of treatment and nontreatment settings in São Paulo, Brazil, were interviewed using a questionnaire that includes the Severity of Dependence Scale (SDS), the General Health Questionnaire (GHQ-28), the CAGE, and an eight-item questionnaire investigating the frequency of specific adverse cocaine reactions. The most commonly described reactions were hot flushes (84%), uncontrollable shaking (76%), and feeling ill (75%). The most severe symptoms and least common were convulsions or fits (18%) and passing out (21%). Frequency of adverse reactions to cocaine was positively associated with out-of-treatment status, severity of cocaine dependence, ever having injected cocaine, using tranquilisers with cocaine, and GHQ score. Adverse reactions to cocaine are common among regular cocaine users. Some of the adverse effects, especially those on the heart and central nervous system, are potentially fatal. Preventive strategies should be developed to reduce the risk of adverse cocaine reactions. The findings are discussed in relation to the type of interventions that might be developed and lines of future research.

Acute Disease↗
PubMed2004

High mortality among young crack cocaine users in Brazil: a 5-year follow-up study.

AIMS: Follow-up studies show that smokers, alcoholics and heroin addicts have high mortality rates, but there is little information on crack users. We have investigated the mortality rate among this population, including its risk factors and causes of death. DESIGN: A 5-year follow-up study. PARTICIPANTS AND SETTING: A cohort of 131 crack-dependent patients, admitted to a public detoxification unit in São Paulo between 1992 and 1994. MEASUREMENTS: Data collected from a structured personal interview and from a review of patients' hospital records, confirming the deaths from records held at the Municipal Offices. FINDINGS: Of the 124 (94.6%) patients located, 23 (18.5%) had died (a mortality ratio of 7.6). Homicide was the most common cause of death (n = 13). Observed mortality rate, adjusted for age and sex, was 24.92 per 1000, while the expected all-cause mortality rate in São Paulo, also adjusted for age and sex, was 3.28 per 1000, giving an excess mortality rate of 21.64 per 1000. Survival analysis showed that the probability of being alive 5 years post-treatment was 0.80 (95% CI = 0.77-0.84). Cox's proportional hazards regression showed three factors predicted mortality: history of intravenous drug use (hazard ratio 3.28, 95% CI 1.42-7.59), unemployment at index admission (hazard ratio 3.48, 95% CI 1.03-11.80) and premature discharge from index admission (hazard ratio 2.21, CI 0.94-5.18). CONCLUSIONS: Community-based and tailored interventions should be considered to improve those patients' social support and permanence in treatment.

Adult↗
PubMed2003

Ralstonia metallidurans, a bacterium specifically adapted to toxic metals: towards a catalogue of metal-responsive genes.

Ralstonia metallidurans, formerly known as Alcaligenes eutrophus and thereafter as Ralstonia eutropha, is a beta-Proteobacterium colonizing industrial sediments, soils or wastes with a high content of heavy metals. The type strain CH34 carries two large plasmids (pMOL28 and pMOL30) bearing a variety of genes for metal resistance. A chronological overview describes the progress made in the knowledge of the plasmid-borne metal resistance mechanisms, the genetics of R. metallidurans CH34 and its taxonomy, and the applications of this strain in the fields of environmental remediation and microbial ecology. Recently, the sequence draft of the genome of R. metallidurans has become available. This allowed a comparison of these preliminary data with the published genome data of the plant pathogen Ralstonia solanacearum, which harbors a megaplasmid (of 2.1 Mb) carrying some metal resistance genes that are similar to those found in R. metallidurans CH34. In addition, a first inventory of metal resistance genes and operons across these two organisms could be made. This inventory, which partly relied on the use of proteomic approaches, revealed the presence of numerous loci not only on the large plasmids pMOL28 and pMOL30 but also on the chromosome. It suggests that metal-resistant Ralstonia, through evolution, are particularly well adapted to the harsh environments typically created by extreme anthropogenic situations or biotopes.

Adenosine Triphosphatases↗
PubMed2003

The double back salto dismount from the parallel bars.

The purpose of this study was to identify those mechanical determinants or their trends that distinguished a gymnast's best performance of the double back salto dismount on parallel bars from those judged to be inferior. Dismounts, in the tucked position, by nine Canadian gymnasts were analysed. Unique to this study was the inclusive analysis of multiple performances of the same skill by these athletes. It was felt that within-subject comparisons would reveal the kinematic variables on which the gymnast may focus in order to achieve their best performances. A non-parametric median sign test was used to compare mechanical variables, within subjects, between the dismount judged the best and those dismounts awarded a lower score. Three judges judged each dismount. In comparison to poorer performances of the dismount, statistical analyses revealed that athlete's best performances were characterised by (1) a higher release point, more vertical velocity yet with less angular momentum at take-off, (2) greater height, with a tighter and earlier tuck position during the flight phase, and (3) a greater range of motion and a more compact squat position at landing (all p's < .06).

Biomechanical Phenomena↗
PubMed2003

Gender differences in the use of alcohol and psychotropics in a Brazilian population.

This cross-sectional, interview-based survey aimed to assess the use of licit substances in terms of gender and sociodemographic factors in the city of Pelotas, southern Brazil. Subjects aged 15 years and over and living in urban areas were eligible and a total of 1277 subjects were interviewed. The prevalence of alcohol consumption was 54.2%; 11.9% (21.7% of men and 4.1% of women) reported potentially harmful levels of alcohol use ("at-risk alcohol intake"); 4.2% were classified as manifesting alcohol dependence by CAGE questionnaire. At-risk alcohol intake and subjects with a positive CAGE score were more common among males aged 35-54 yrs. Among the youngest age group, the prevalence of CAGE positive score was similar for males and females, while subjects with lower educational levels showed a higher prevalence. Women were more likely than men to report the use of psychotropic drugs (15% vs. 7%). These results highlight the importance of substance use in Brazil, and suggest that gender differences must to be taken into consideration when planning intervention programs in developing countries.

Adolescent↗
PubMed2002

Epidemiologic investigation of Mycobacterium bovis in a population of cats.

OBJECTIVE: To determine whether cats exposed at a residence were infected with Mycobacterium bovis, whether the tuberculin skin test can identify cats infected with M bovis, and whether an ELISA could identify tuberculosis-infected cats. ANIMALS: 20 domestic cats exposed to a cat with laboratory-confirmed disseminated M bovis infection. PROCEDURE: Cats were administered a tuberculin skin test and monitored for 72 hours. Blood and fecal samples were collected. Cats were then euthanatized, and postmortem examinations were performed. Tissues were examined grossly and histologically for signs of mycobacteriosis. Pooled tissue samples and fecal samples were submitted for mycobacterial culture. Blood samples were examined for evidence of tuberculosis by use of a comparative ELISA. RESULTS: 4 cats had positive responses for the ELISA, and 2 cats had suspicious responses. All tuberculin skin tests yielded negative results. No gross or histologic lesions of tuberculosis were detected in any tissues, and mycobacteria were not isolated from tissues or feces obtained from the 20 cats. CONCLUSIONS AND CLINICAL RELEVANCE: All cats that had positive or suspicious responses for the ELISA were offspring of the cat with tuberculosis. Evidence of tuberculosis was not seen in other cats at the residence, the owner, or the attending veterinarian. The most likely source of tuberculosis for the infected cat was through the consumption of M bovis-infected wildlife carcasses or offal. Because M bovis is endemic in wildlife in northeastern Michigan, there is a risk of exposure to tuberculosis in companion animals, their owners, and attending veterinarians.

Animals↗