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Biomedical subjects

J Dixon

Publications and source records attributed to J Dixon.

At least 55 records · Page 3Linked to original sources
PubMed2000

Epidemiology of diphtheria in South Dakota.

Respiratory diphtheria was one of the most common causes of death among children in the pre-vaccine era. Since the introduction of diphtheria toxoid vaccine in 1920s, and its widespread use by the late 1940s, diphtheria became increasingly rare in the United States. However, through the 1970s diphtheria remained endemic in some states, with reported incidence rates > 1.0 per million population in six states (Alaska, Arizona, Montana, New Mexico, South Dakota, and Washington). Starting in 1980, less than five cases have been reported each year in the United States. The majority of culture-confirmed cases have been associated with importation from other countries. Toxigenic Corynebacterium diphtheriae, the organism causing diphtheria, was thought to have become rare or even have disappeared from previously endemic areas such as South Dakota. However, during four months in 1996, 11 persons (one index case, six patients and four household contacts) in an American Indian community in South Dakota were found to be infected by C. diphtheriae; six of these isolates were toxigenic. The findings in this report indicate that despite 20 years without reported respiratory diphtheria cases, toxigenic C. diphtheriae is still present in South Dakota. The continuous circulation of toxigenic strains of C. diphtheriae emphasizes the need for health care providers throughout South Dakota to promote timely vaccination against diphtheria among persons of all ages and ethnic groups, to be aware of the clinical signs and symptoms of diphtheria so that cases can be promptly diagnosed and treated, and further public health measures can be taken to contain this serious disease.

Adolescent↗
PubMed2000

Researching the rural-metropolitan health differential using the 'social determinants of health'.

Recent research indicates that the health status of rural people is inferior to that of people living in metropolitan Australia. This paper summarises the rural-metropolitan health differential and turns to the field of research being called the social determinants of health for explanations of rural health inequalities. The paper explores the ways in which psychosocial factors can interact with material, behavioural and sociocultural factors to contribute to health outcomes. It suggests that the concepts of place and rurality may be useful in future research on the determinants of population health. Further research issues are identified that need to be addressed if we are to understand the complexities of rural health disadvantage.

Australia↗
PubMed2000

Haemochromatosis: work and social implications.

Hereditary haemochromatosis is prevalent in our society and requires vigorous and lifelong treatment. Diagnosis of the disorder may be delayed or missed due to its nonspecific symptoms and diverse manifestations. This can have lifelong consequences for the sufferer. Early diagnosis prevents severe organ damage and premature death and leads to a normal productive life. Screening family members will enable early diagnosis of those with the HFE gene mutation. The stigma attached to having a genetic condition may have consequences for job opportunities and for life and health insurance. Education of the community (including workplaces and employers) as well as health service providers will not only increase the likelihood of early diagnosis of haemochromatosis but will ease the social consequences of suffering from this disorder.

Employment↗
PubMed1999

Neo-striatal rCBF correlates of psychomotor slowing in patients with major depression.

Psychomotor slowing is a fundamental clinical feature of severe depression and is thought to reflect dysfunction within prefrontal-subcortical circuits. This study utilised a split-dose single photon emission computerised tomography (SPECT) scanning technique in association with a two-stage test of psychomotor speed. Twenty-five patients with primary depressive disorders were injected with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) whilst performing each component of a two-stage psychomotor task. The first stage, 'simple reaction time' (RT) and the second stage, 'choice reaction time' (CRT), were each followed by 30-min SPECT scans. Regions of interest (ROIs) corresponding to the left and right neo-striatum (caudate-putamen) were drawn, and regional cerebral blood flow (rCBF) values were calculated. Importantly, the change in rCBF measure in the left neo-striatum was inversely correlated with RT (r = -0.48, P < 0.05). That is, the patients with the greatest psychomotor slowing initially showed the least increase in rCBF during the CRT condition. This effect was independent of age. The study demonstrates that a simple two-stage motor paradigm can be used to elicit rCBF correlates of psychomotor slowing in patients with primary depression. Such rCBF findings may implicate the neo-striatum in the neurobiology of major depression.

Adult↗
PubMed1999

Unexplained fainting, near drowning and unusual seizures in childhood: screening for long QT syndrome in New Zealand families.

AIMS: To construct detailed pedigrees of five New Zealand families with autosomal dominant long QT syndrome (LQTS) and screen selected individuals based on initial symptomatic and ECG data. METHODS: Clinical data were collected using a questionnaire and relevant medical record review. Participants were then classified according to ECG diagnostic criteria based on the presence or absence of symptoms and the rate-corrected QT interval (QTc) into three groups: affected, uncertain or unaffected. Blood samples were also collected from each participant and DNA extracted for genetic testing. RESULTS: Seventy-eight family members were screened. The majority of the 35 symptomatic family members, who were affected on these criteria, had presented with symptoms in childhood. Of the remaining 43 asymptomatic family members, the majority were in the uncertain diagnostic group based on these ECG criteria. CONCLUSIONS: Autosomal dominant long QT syndrome (Romano Ward syndrome) is being increasingly recognised and must be considered in the investigation of children who present with unexplained fainting, near drowning, unusual seizures and sudden death. Screening long QT syndrome families based on ECG criteria remains difficult leaving a number of family members with an uncertain diagnosis. It is hoped that genetic testing will become useful for diagnosis of presymptomatic carriers of long QT syndrome in New Zealand in the future.

Adolescent↗
PubMed1999

Antagonists of the platelet P2T receptor: a novel approach to antithrombotic therapy.

The platelet P2T receptor plays a major role in platelet aggregation, and its antagonists are predicted to have significant therapeutic potential as antithrombotic agents. We have explored analogues of adenosine triphosphate (ATP), which is a weak, nonselective but competitive P2T receptor antagonist. Modification of the polyphosphate side chain to prevent breakdown to the agonist adenosine diphosphate (ADP) and substitution of the adenine moiety to enhance affinity and selectivity for the P2T receptor led to the identification of 10e (AR-C67085MX), having an IC50 of 2.5 nM against ADP-induced aggregation of human platelets. Compound 10e was the first very potent antagonist of the P2T receptor, with a selectivity for that subtype of the P2 receptor family of >1000-fold. Further modification of the structure produced compound 10l (AR-C69931MX) having an IC50 of 0.4 nM. In vivo, at maximally effective antithrombotic doses, there is little prolongation of bleeding time (1.4-fold), which is in marked contrast to the 5-6-fold found with GPIIb/IIIa antagonists.

Adenosine Monophosphate↗
PubMed1999

Identification and cloning of a novel cellular protein Naf1, Nef-associated factor 1, that increases cell surface CD4 expression.

The nef gene of human and simian immunodeficiency virus is a key factor in acquired immunodeficiency syndrome pathogenesis and virus replication. Several Nef-induced phenomena, including the down-regulation of CD4 molecule, have been previously reported. In this study, we have identified and cloned a novel cellular protein Naf1 (Nef-associated factor 1), which associated with Nef in the yeast two-hybrid system and pull-down assay. The Naf1 gene generates two isoforms (Naf1alpha and beta) containing four coiled-coil structures. The Naf1 mRNA is ubiquitously expressed in human tissues with strong expression in peripheral blood lymphocytes and spleen. Naf1 overexpression increased cell surface CD4 expression. Nef suppressed this Naf1-induced augmentation of CD4 expression, providing a novel mode of Nef action in CD4 down-regulation.

Amino Acid Sequence↗
PubMed1999

Etiology of acute lower respiratory tract infection in Central Australian Aboriginal children.

BACKGROUND: Aboriginal children in central Australia have attack rates for acute lower respiratory tract infection (ALRI) that are similar to those in developing countries. Although mortality rates are much lower than in developing countries, morbidity is high and ALRI is still the leading cause of hospitalization. However, there are no data on the etiology of ALRI in this population. METHODS: We prospectively studied 322 cases of ALRI in 280 Aboriginal children admitted to the hospital. Blood, urine and nasopharyngeal aspirate samples were examined for evidence of bacterial, viral and chlamydial infection. RESULTS: The combination of blood culture, viral studies and chlamydial serology provided at least 1 etiologic agent in 170 of 322 (52.5%) cases. Assays for pneumolysin immune complex and pneumolysin antibody increased etiologic diagnosis to 219 (68.0%). Blood cultures were positive in 6% but pneumolysin immune complex and pneumolysin antibody studies were positive in one-third of cases. Evidence of viral infection was present in 155 (48%) of cases compared with 12% in controls (P < 001). There were only 7 possible cases and 2 definite cases of Chlamydia trachomatis and 3 cases of Chlamydia pneumoniae. Coinfection was common in these children. CONCLUSION: These findings have implications for both standard treatment protocols and vaccine strategies. The high rate of coinfection may make it difficult to develop simple clinical predictors of bacterial infection. In the setting of a developed country with efficient patient evacuation services, management algorithms that focus on disease severity and need for hospital referral will be most useful to health staff in remote communities. Pneumococcal conjugate vaccines will be required to reduce the high attack rate of pneumococcal disease.

Australia↗
PubMed1999

A global perspective on social security programs for the aged.

The social security programs that have become widely established in countries around the globe vary greatly in their design features. The difference among the programs invites questions regarding the relative strength of their designs. One hundred and sixty-four programs are assessed on three design dimensions: benefit eligibility, qualifying eligibility criteria, and benefit provision. The analysis shows that the best-designed old-age programs can be found in Western Europe and Australasia.

Aged↗
PubMed1998

Substrate specificity of the SpCCE1 holliday junction resolvase of Schizosaccharomyces pombe.

SpCCE1 from Schizosaccharomyces pombe is an endonuclease that resolves Holliday junctions in vitro. SpCCE1 also binds and cleaves a range of other DNAs (Y-junction; flap; and flayed, nicked, and partial duplexes) with varying efficiency. Cleavage sites are always 3' of thymine nucleotides positioned at or close to the branch point or strand interruption. SpCCE1's favored substrate is the X-junction. Up to two dimers of SpCCE1 can bind concurrently to the same X-junction at its crossover point. From mixing experiments of SpCCE1 and the Escherichia coli RuvA protein, we show that each dimer of SpCCE1 binds to a different face of the X-junction and that both are seemingly competent for strand cleavage. We propose that this provides a mechanism whereby SpCCE1 can scrutinize all four junction strands simultaneously for cleavable thymine nucleotides. SpCCE1 appears to resolve X-junctions by a nick and counter-nick mechanism. Therefore, to ensure a high probability of bilateral strand cleavage, SpCCE1 has a relatively long lifetime on X-junctions. This mechanism has the drawback of limiting dissociation from noncleavable junctions. We discuss why this might not be a problem in vivo.

Base Sequence↗
PubMed1998

Molecular basis of transient outward potassium current downregulation in human heart failure: a decrease in Kv4.3 mRNA correlates with a reduction in current density.

BACKGROUND: Despite advances in medical therapy, congestive heart failure remains a major cause of death in the developed world. A disproportionate number of the deaths of patients with heart failure are sudden and presumed to be arrhythmic. Heart failure in humans and in animal models is associated with prolongation of the action potential duration (APD), the result of downregulation of K+ currents-prominently, the Ca2+-independent transient outward current (Ito). The mechanism for the reduction of Ito in heart failure is unknown. The K+ channel alpha-subunit Kv4.3, a homolog of the Drosophila Shal family, is most likely to encode all or part of the native cardiac Ito in humans. METHODS AND RESULTS: We used ribonuclease protection assays and whole-cell electrophysiological recording to study changes in the level of Kv4.3 mRNA and Ito in human tissues and isolated ventricular myocytes, respectively. We found that the level of Kv4.3 mRNA decreased by 30% in failing hearts compared with nonfailing controls. Furthermore, this reduction correlated with the reduction in peak Ito density measured in ventricular myocytes isolated from adjacent regions of the heart. There was no significant change in the steady-state level of any other mRNA studied (HERG, Kv1.4, Kir2.1, Kvss1.3, and the alpha1C subunit of the Ca2+ channel). mRNAs encoding Kv1.2, Kv1.5, and Kv2.1 were found in low abundance in human ventricle. CONCLUSIONS: These data provide further support for the hypothesis that Kv4.3 encodes all or part of the native cardiac Ito in humans and that part of the downregulation of this current in heart failure may be transcriptionally regulated.

Action Potentials↗