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Biomedical subjects

J Mott

Publications and source records attributed to J Mott.

At least 19 recordsLinked to original sources

Boys with high body masses have an increased risk of developing asthma: findings from the National Longitudinal Survey of Youth (NLSY).

OBJECTIVE: To determine the relation between body mass index and the development of asthma in children. DESIGN: Prospective study of 4393 asthma-free children followed for up to 14 years. SETTING: Children of participants in the National Longitudinal Survey of Youth. METHODS: Analysis was limited to children who were followed from birth and were asthma-free during the first 24 months of life. The outcome was the development of asthma during follow-up (incident asthma). Body mass index (BMI) was our main predictor of interest. Survival analyses, using time to development of asthma as the main endpoint, were stratified by sex and controlled for race/ethnicity, poverty status, and prenatal maternal smoking. RESULTS: Asthma developed in 218 (5.0 %) children during the follow-up period. The relation between BMI and incident asthma varied by sex. A BMI > or =85th percentile at age 2-3 years was a risk factor for subsequent asthma development in boys (hazard ratio (HR) 1.6 95% confidence interval (CI) 1.1, 2.4) but not girls (HR 0.8, 95% CI 0.5, 1.4). Similarly, boys with BMIs always > or =85th percentile were at increased risk for subsequent asthma development (HR 2.4, 95% CI 1.4, 4.4) but not girls (HR 1.5, 95% CI 0.7, 2.9). CONCLUSION: Boys with high body masses may be at an increased risk for developing asthma.

Asthma↗

Patients receiving a prescription for diamorphine (heroin) in the United Kingdom.

The United Kingdom is unusual internationally in that it is one of few countries able to prescribe diamorphine for the treatment of opiate dependence. Prescribing diamorphine has been part of the UK response to drug problems since the 1920s. Despite this, little is known about who receives diamorphine and how treatment is delivered. This study aims to describe the characteristics and treatment regimes of opiate-dependent drug users receiving a prescription for diamorphine in the United Kingdom in 2000, and report on their status in 2002. A retrospective case-note review was conducted in England and Wales. Two hundred and ten (72%; 210/292) patients' sets of case-notes were reviewed at 27 of the 42 (64%) drug clinics where diamorphine was prescribed by the doctor. Patients had been receiving a prescription for diamorphine for a median length of six years. The majority were unemployed white males, with a median age of 44 years. Illicit drug use and criminal activity, while low, had not been eliminated totally. The majority were prescribed ampoules and few had significant health problems. In some cases patients had been transferred to injectable diamorphine from injectable methadone to reduce injection related problems. There were wide variations in dose. The majority of patients had no serious drug, health or social problems. Diamorphine prescribing was a long-term commitment. The experience from the United Kingdom has been one of long-term prescribing with the aim of retaining patients in treatment and reducing the harms caused by illicit drug use. Prospective studies are needed to determine the long-term consequences of receiving a diamorphine prescription.

Ambulatory Care Facilities↗

Multidisciplinary assessment at a child development centre: do we conform to recommended standards?

BACKGROUND: A proposed standard for the multidisciplinary assessment (MDA) of children with autism has been recently published by the National Autistic Society. This prompted a review of current practice at the child development centre in our local centre, to judge whether we were able to conform to the proposed national standard. The recommendation is that a child should complete a three-stage assessment process from referral to completion of assessment within 30 weeks, with set times for completion of each stage (6, 7 and 17 weeks respectively). We applied this assessment model to children with a range of neurodevelopment problems, as the process of MDA is the same, irrespective of diagnosis. METHODS: A retrospective analysis of medical and therapy records of all MDAs was carried out between April 2001 and March 2002. RESULTS: In the 12-month period studied, 52 MDAs were performed. Delays occurred, as judged by the standard, at all three stages of the assessment process. A total of 42% of children were seen within 6 weeks of initial referral, 37% within a further 7 weeks for specialist assessment, and 37% within a further 17 weeks for completion of MDA. As delays occurred at all stages, the cumulative total showed that only 19% of children completed all three stages within the recommended 30-week standard. Barriers encountered included waiting times to see professionals, parental non-attendance and prolonged assessment of complex problems. Some of these factors are outside our control, and on removing these factors the data were re-analysed. This resulted in a slight improvement to 45%, 48% and 49% for completion of stages 1, 2 and 3 respectively. The major reason for delay remained the service capacity. CONCLUSION: In our experience the standards proposed by the National Autistic Society are not practical within present resources. We suggest that a reasonable expectation is to complete all assessments, from first concern to completed MDA, should be carried out within 52 weeks with present levels of resources. Any further improvement will require additional resources to reduce waiting times and increase the capacity.

Autistic Disorder↗

The relation of perceived neighborhood danger to childhood aggression: a test of mediating mechanisms.

In the current study, two mediational mechanisms, parenting practices and children's beliefs about aggression, were hypothesized to account for the relationship between perceived neighborhood danger and childhood aggression. Using structural equation modeling, data were analyzed from an inner-city school-based sample of 732 predominantly African American 5th graders. Results suggested that perceived neighborhood danger was associated with strong positive beliefs about aggression, which in turn was associated high levels of aggression. The hypothesized mediating role of parenting practices (restrictive discipline, parental monitoring, and parental involvement) on the relation between perceived neighborhood danger and child aggression was not supported. However, the current findings suggest that children's positive beliefs about aggression mediated the relationship between restrictive discipline and aggression. Directions for future research are discussed.

Adult↗

Human granulocytic ehrlichiosis agent inhibits superoxide anion generation by human neutrophils.

The human granulocytic ehrlichiosis (HGE) agent, which replicates in neutrophils, was found not to induce superoxide anion (O(2)(-)) generation or extracellular release by human peripheral blood neutrophils, as measured by a luminol-dependent chemiluminescence assay or a cytochrome c reduction assay, respectively. Furthermore, the HGE agent completely prevented O(2-) release by neutrophils upon stimulation with phorbol myristate acetate (PMA), formylmethionyl-leucyl-phenylalanine, or Escherichia coli. The inhibition was HGE agent dose dependent, required ehrlichial contact with the host cells, and was reversible upon removal of the extracellular HGE agent bound to the host cells prior to PMA stimulation. Structural integrity of or new protein synthesis by the HGE agent was not required for the inhibition; carbohydrate but not surface protein of the HGE agent was required. The HGE agent did not prevent O(2-) generation in human peripheral blood monocytes derived from the same individual. This neutrophil-specific prevention of O(2-) generation by the HGE agent would be critical in survival of the HGE agent. This is the first demonstration of the rapid inhibition of preexisting NADPH oxidase in human neutrophils by the HGE agent.

Ehrlichia↗

Intracellular infection by the human granulocytic ehrlichiosis agent inhibits human neutrophil apoptosis.

In patients with human granulocytic ehrlichiosis (HGE), the HGE agent has been seen only in the peripheral blood granulocytes, which have a life span too short for ehrlichial proliferation. To determine if the HGE agent delays the apoptosis of human peripheral blood neutrophils for its advantage, peripheral blood granulocytes consisting mostly of neutrophils were incubated with freshly freed host cell-free HGE agent in vitro. The HGE agent induced a significant delay in morphological apoptosis and the cytoplasmic appearance of histone-associated DNA fragments in the granulocytes. This antiapoptotic effect was dose dependent. Although much weaker than the HGE agent freshly freed from the host cells, noninfectious purified HGE agent stored frozen and thawed also had antiapoptotic effect, which was lost with proteinase K treatment but not with periodate treatment. Treatment of neutrophils with a transglutaminase inhibitor, monodansylcadaverine, blocked the antiapoptotic effect of the HGE agent. Addition of oxytetracycline, however, did not prevent or reverse the antiapoptotic effect of the HGE agent. These results suggest that binding of a protein component(s) of the HGE agent to neutrophils and subsequent cross-linking and/or internalization of the receptor and ehrlichiae are required for antiapoptotic signaling, but ehrlichial protein synthesis and/or proliferation is not required. MG-132, a proteasome inhibitor, and cycloheximide accelerated the apoptosis of neutrophils and overrode the antiapoptotic effect of the HGE agent. Studies with specific inhibitors suggest that protein kinase A, NF-kappaB, and interleukin 1beta are not involved in the antiapoptotic mechanism of the HGE agent.

Apoptosis↗

Analysis of 16S rRNA and 51-kilodalton antigen gene and transmission in mice of Ehrlichia risticii in virgulate trematodes from Elimia livescens snails in Ohio.

Operculate snails (the family Pleuroceridae: Elimia livescens) were collected between June and October 1998 from a river in central Ohio where repeated cases of Potomac horse fever (PHF) have occurred. Of collected snails, consistently 50 to 80% carried a combination of cercariae and sporocysts of digenetic virgulate trematodes. The trematodes obtained from each snail were pooled and tested for Ehrlichia risticii, the agent of PHF, by nested PCR using primers specific to the 16S rRNA gene. Out of a total of 209 trematode pools, 50 pools were found to be positive by PCR. The DNA sequence of the 16S rRNA gene identified in one trematode pool was identical to that of the type strain of E. risticii, and the sequence of the gene identified in another pool differed from that of the type strain by 1 nucleotide. Comparison of the deduced amino acid sequence of the partial 51-kDa antigen gene from various sources revealed that Maryland, Ohio (except Ohio 081), and Kentucky strains are in a cluster distinct from the sequences obtained from sources in California and Oregon. Ohio 081 was shown previously by antigenic composition analysis to be distinct from other groups. However, all sequences examined were not segregated according to their sources: horse blood or infected trematodes. E. risticii was found to be transmittable from trematodes to mice and was subsequently passaged from infected mice to additional mice, as determined by PCR analysis. Our findings suggest the evolution of E. risticii in the natural reservoir in separate geographic regions and persistent infection of trematode populations with E. risticii during summer and early fall. The study also suggests that the mouse can be used to isolate E. risticii from the infected trematode.

Amino Acid Sequence↗

The application of Poisson random-effects regression models to the analyses of adolescents' current level of smoking.

BACKGROUND: In school-based smoking prevention research, it is still debatable whether parents or peers are most influential to maintained smoking among adolescents. As a result, this study examines the effects of parental and peer approval of smoking on adolescents' current levels of smoking. METHODS: Poisson random-effects regression models were used to assess the effects of parental and peer approval of smoking on adolescents' (n = 913) current level of smoking. RESULTS: Results of these analyses indicate that a stronger relationship between parental approval of smoking and current level of smoking was found for female adolescents than for male adolescents. Conversely, a stronger relationship between peer approval of smoking and current level of smoking was found for male adolescents than for female adolescents. With respect to race, the influence of parental approval of smoking on adolescents' current level of smoking was generally more pronounced for minority adolescents, relative to white adolescents. However, the influence of peer approval of smoking on current level of smoking was strongest for white adolescents and was less strong for black, Hispanic, and Asian adolescents. CONCLUSION: The findings of this study demonstrated that the effects of parental and peer approval of smoking on adolescents' current levels of smoking were varied by gender and race. These differential effects may have some implication for the development of future school-based smoking prevention and cessation programs.

Adolescent↗

Human granulocytic ehrlichiosis agent and Ehrlichia chaffeensis reside in different cytoplasmic compartments in HL-60 cells.

The human granulocytic ehrlichiosis (HGE) agent resides and multiplies exclusively in cytoplasmic vacuoles of granulocytes. Double immunofluorescence labeling was used to characterize the nature of the HGE agent replicative inclusions and to compare them with inclusions containing the human monocytic ehrlichia, Ehrlichia chaffeensis, in HL-60 cells. Although both Ehrlichia spp. can coinfect HL-60 cells, they resided in separate inclusions. Inclusions of both Ehrlichia spp. were not labeled with either anti-lysosome-associated membrane protein 1 or anti-CD63. Accumulation of myeloperoxidase-positive granules were seen around HGE agent inclusions but not around E. chaffeensis inclusions. 3-(2, 4-Dinitroanilino)-3'-amino-N-methyldipropylamine and acridine orange were not localized to either inclusion type. Vacuolar-type H+-ATPase was not colocalized with HGE agent inclusions but was weakly colocalized with E. chaffeensis inclusions. E. chaffeensis inclusions were labeled with the transferrin receptor, early endosomal antigen 1, and rab5, but HGE agent inclusions were not. Some HGE agent and E. chaffeensis inclusions colocalized with major histocompatibility complex class I and II antigens. These two inclusions were not labeled for annexins I, II, IV, and VI; alpha-adaptin; clathrin heavy chain; or beta-coatomer protein. Vesicle-associated membrane protein 2 colocalized to both inclusions. The cation-independent mannose 6-phosphate receptor was not colocalized with either inclusion type. Endogenously synthesized sphingomyelin, from C6-NBD-ceramide, was not incorporated into either inclusion type. Brefeldin A did not affect the growth of either Ehrlichia sp. in HL-60 cells. These results suggest that the HGE agent resides in inclusions which are neither early nor late endosomes and does not fuse with lysosomes or Golgi-derived vesicles, while E. chaffeensis resides in an early endosomal compartment which accumulates the transferrin receptor.

Animals↗

Comparison of PCR and culture to the indirect fluorescent-antibody test for diagnosis of Potomac horse fever.

Potomac horse fever is an acute systemic equine disease caused by Ehrlichia risticii. Currently, serologic methods are widely used to diagnose this disease. However, serologic methods cannot determine whether the horse is presently infected or has been exposed to ehrlichial antigens in the past. The purpose of the present study was to compare the sensitivities of the nested PCR and cell culture with that of the indirect fluorescent-antibody (IFA) test for the diagnosis of Potomac horse fever. Blood and fecal specimens serially collected from a pony experimentally infected with E. risticii Maryland, blood specimens serially collected from mice inoculated with E. risticii Ohio 380, and blood and/or fecal specimens collected from 27 horses which had clinical signs compatible with Potomac horse fever were examined. These horses resided in Kentucky, Indiana, Pennsylvania, and Vermont. The IFA test titer became positive after 6 days postinoculation (p.i.) for the pony. A culture of the blood of the pony was positive for E. risticii starting on day 1 and was positive through day 28 p.i. By the nested PCR, E. risticii was detectable in the blood and feces of the pony starting on day 1 and was detectable through day 32 p.i. E. risticii was detected in the blood of subclinically infected mice by the nested PCR. Twenty-two clinical specimens were seropositive for E. risticii by the IFA test, with titers ranging from 1:20 to 1:1,280. E. risticii was cultured from 95% (20 of 21) of seropositive clinical blood specimens. E. risticii was detected in the blood by PCR in 81% (17 of 20) of the culture-positive clinical specimens. The study indicated that the nested PCR is as sensitive as culture for detecting infection with E. risticii.

Animals↗

Carotid duplex criteria for a 60% or greater angiographic stenosis: variation according to equipment.

PURPOSE: The purpose of this study was to evaluate the carotid duplex criteria for a > or = 60% angiographic internal carotid artery (ICA) stenosis and the degree of variation among duplex scanners. METHODS: Carotid duplex criteria for a > or = 60% angiographic stenosis were evaluated in two ICAVL-accredited vascular laboratories with different brands of duplex scanners (Siemens-Quantum and Diasonics in Laboratory A, ATL and Diasonics in Laboratory B). Analysis was performed for 360 carotid bifurcations in 180 consecutive patients who had concurrent angiographic and duplex evaluation. Blinded angiogram evaluation was performed with precision electronic calipers on magnified views, with stenosis calculated by criteria of the Asymptomatic Carotid Atherosclerosis Study and the North American Symptomatic Carotid Endarterectomy Trial. Duplex data included internal carotid artery peak systolic velocity (ICA PSV), ICA end-diastolic velocity, and the ratio of ICA PSV to common carotid artery (CCA) PSV (ICA/CCA ratio). RESULTS: The most accurate determination of a > or = 60% ICA stenosis was obtained with ICA/CCA ratio and ICA PSV, but the optimal threshold differed for all four scanners. The optimal ICA/CCA ratio varied from 2.6 to 3.3, and the optimal ICA PSV varied from 190 to 240 cm/sec. All four scanners produced criteria that give a positive predictive value > 90% while maintaining accuracy at > or = 90%. Logarithmic transformation of duplex variables created a linear relationship between duplex values and angiographic stenosis, allowing statistical evaluation of scanner operating characteristics by linear regression analysis and analysis of covariance. This analysis revealed that the mathematic equation relating duplex values with angiographic percent stenosis was statistically different for one of the four scanners (p < 0.05). Scanner differences did not appear to be due to technologists, because the regression lines were nearly identical for the two Diasonics scanners despite use by different technologists. Ignoring the significant difference in operating characteristics for one of the four scanners would result in a mean error for predicting a 60% stenosis of 14% to 18% (equating a 46% or 78% stenosis with a 60% stenosis). CONCLUSIONS: We conclude that the correlation of duplex data with angiographic percent stenosis and the duplex criteria for a > or = 60% stenosis are machine-specific. Regression analysis can determine whether apparent differences are due to chance or significant differences in scanner characteristics. Future studies should include regression analysis according to equipment type.

Aged↗

Evidence for a high rate of false-positive results with the indirect fluorescent antibody test for Ehrlichia risticii antibody in horses.

OBJECTIVE: The original objective was to determine seroprevalence of Ehrlichia risticii antibody among horses in California. On the basis of the unexpected results of the survey, an investigation into the accuracy and reproducibility of results of the indirect fluorescent antibody (IFA) test for E risticii was carried out. DESIGN: Prospective, seroprevalence study. ANIMALS: Healthy horses (n = 655) and horses with clinical signs of equine monocytic ehrlichiosis (EME; n = 514) from various regions of California. PROCEDURE: The IFA test was performed. Results were compared with results of an ELISA and with results of western immunoblot analysis. RESULTS: Overall, 104 of 655 (15.9%) healthy horses had evidence of an antibody response. However, 84 of 514 (16.3%) horses with clinical signs of EME also had positive test results, and of the 8 seropositive diseased horses for which paired (acute and convalescent) samples had been submitted, only 1 had a rise in antibody titers between the acute and convalescent samples. Comparison of results for the IFA test, ELISA, and western immunoblot analysis revealed a high rate of false-positive results for the IFA test. Subsequent studies suggested that routine vaccination of horses with non-E risticii vaccines may have contributed to the false-positive reactions. CLINICAL IMPLICATIONS: The data failed to provide conclusive evidence of E risticii infection among California horses. Owing to the high percentage of false-positive test results, caution is advised when using the IFA test to diagnose EME in horses or to determine the necessity for E risticii vaccination.

Animals↗

Ehrlichia muris sp. nov., identified on the basis of 16S rRNA base sequences and serological, morphological, and biological characteristics.

The 16S rRNA gene of a new infectious agent, strain AS145T (T = type strain), which was isolated from a wild mouse in Japan, was amplified by using the PCR. The amplimers were directly sequenced by dideoxynucleotide methods with Taq DNA polymerase. Sequence comparisons with other members of the tribe Ehrlichieae and related species revealed that the infectious agent isolated from the mouse is a new species of the genus Ehrlichia that is most closely related to Ehrlichia chaffeensis (level of sequence similarity, 97.9%), an agent of human ehrlichiosis in the United States. This result was consistent with the results of an immunoblot analysis performed with immune sera against different ehrlichiosis agents. On the basis of these findings and other morphological, biological, and serological characteristics of the organism, we propose that ehrlichiae with these properties belong to a new species, Ehrlichia muris.

Anaplasmataceae↗

C-reactive protein and alpha 1-acid glycoprotein levels in dogs infected with Ehrlichia canis.

To elucidate whether acute-phase protein responses occur in dogs infected with Ehrlichia canis, C-reactive protein (CRP) and alpha 1-acid glycoprotein (AAG) levels were serially measured in the plasma of five dogs experimentally inoculated with E. canis and 10 sham-inoculated or noninoculated control dogs. The CRP concentration was measured by a canine-specific capture enzyme-linked immunosorbent assay, and the AAG concentration was measured by a canine-specific radial immunodiffusion method. In all E. canis-inoculated dogs, a 3.3- to 6.5-fold increase in the plasma CRP concentration and a 1.9- to 8.6-fold increase in the plasma AAG concentration over the preinoculation level occurred at days 4 to 6 postexposure. Despite the persistence of E. canis and high antibody titers, both CRP and AAG concentrations gradually declined to preexposure levels by day 34 postexposure. E. canis-infected dogs had mild and transient clinical signs which resolved without treatment by day 14 postexposure. The CRP and AAG concentrations in control inoculated or nontreated dogs remained within the normal range throughout the experimental period. Of 12 dogs naturally infected with E. canis, 75% had greater than 50 micrograms of CRP per ml and 83% had greater than 500 micrograms of AAG per ml. All of these 12 dogs had chronic and severe clinical signs of canine ehrlichiosis. Thus, elevations in the levels of acute-phase proteins occur in both acute and chronic canine ehrlichiosis. Determination of CRP and AAG concentrations may help in assessing the severity of inflammatory damage in dogs with E. canis infections.

Acute-Phase Reaction↗

A comparison of doctors' practice in notifying addicts to the Home Office and reporting them to the North Western Drug Misuse Database.

Doctors have been required to notify named addict patients to the Chief Medical Officer at the Home Office since 1968, and since 1990 have been encouraged to report voluntarily all their drug misusing patients to anonymized NHS regional databases. The North Western Drug Misuse Database, set-up for research purposes in 1985, was the forerunner of these databases. Compliance by doctors from three North Western District Health Authorities with both data collection systems between 1986 and 1989 was assessed by matching the names of notified addicts with the attributors of individuals reported to the NWDMD as users of notifiable drugs. By 1989 72% of addicts notified were also reported to the NWDMD although doctors working in hospital general departments still tended only to notify them. There was no evidence that particular general practitioners consistently did not notify their addict patients while reporting them to the NWDMD. The findings suggest that it will take some time for doctors to become accustomed to reporting all their drug misusing patients to the regional databases as well as notifying to Home Office those who met the notification criteria.

Data Collection↗

Effects of neuroleptics on glutaminase from rat synaptosomes.

Phosphate-activated glutaminase was isolated from synaptosomes from three areas of rat brain. Glutamine utilization phosphate activation and inhibition by glutamate or ammonia were assessed in the absence or presence of haloperidol, chlorpromazine, or clozapine. All three drugs (at 1 micromolar concentration) elevated the Km for glutamine using preparations from the amygdala, hippocampus, or striatum. They interfered with phosphate activation only in the amygdala preparation. No drug affected end-product inhibition. The data suggest that neuroleptics may depress the release of glutamic acid from synaptosomes by interfering with the activation of glutaminase by phosphate.

Amygdala↗