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Biomedical subjects

J D Mathews

Publications and source records attributed to J D Mathews.

At least 19 recordsLinked to original sources

Proteinuria is associated with persistence of antibody to streptococcal M protein in Aboriginal Australians.

Aboriginal communities in Northern Australia with high rates of group A streptococcal (GAS) skin infection in childhood also have high rates of renal failure in adult life. In a cross-sectional study of one such high risk community, albuminuria was used as a marker of renal disease. The prevalence of albuminuria increased from 0/52 in subjects aged 10-19 years to 10/29 (32.9%) in those aged 50 or more (P < 0.001). Antibodies to streptococcal M protein, markers of past GAS infection, were present in 48/52 (92%) at ages 10-19 years, 16/32 (50%) at ages 30-39, and 20/29 (69%) in those aged 50 or more. After allowing for the age-dependencies of albuminuria and of M protein antibodies (P < 0.001) albuminuria was significantly associated with M protein antibodies (P < 0.01). Thus, 72% of adults aged 30 or more with M protein antibodies also had albuminuria, compared with only 21% of those who were seronegative. More detailed modelling suggested that although most Aboriginal people in this community developed M protein antibodies following GAS infection in childhood, the development of proteinuria was associated with the persistence of such seropositivity into adult life. The models predicted that proteinuria developed at a mean age of 30 years in seropositive persons, at 45 years in seronegative persons who were overweight, and at 62 years in seronegative persons of normal weight. We demonstrated a clear association between evidence of childhood GAS infection and individual risk of proteinuria in adult life. This study provided a strong rationale for prevention of renal disease through the more effective control of GAS skin infections in childhood and through the prevention of obesity in adult life.

Adolescent

The multidimensional nature of renal disease: rates and associations of albuminuria in an Australian Aboriginal community.

BACKGROUND: An epidemic of end-stage renal disease (ESRD) is accompanying the rising rates of hypertension, type 2 diabetes and cardiovascular disease among Aborigines in the Northern Territory of Australia. Incidence rates are now 21 times those of nonAboriginal Australians and are doubling every four years. We describe the rates and associations of renal disease in one remote community, which has a current ESRD incidence of 2700 per million, and cardiovascular mortality among the highest in Australia. METHODS: Between 1992 and 1995 a community-wide screening program was conducted, in which the urinary albumin/creatinine ratio (ACR) was used as the chief renal disease marker. More than 90% of the population ages five and older participated. RESULTS: Albuminuria was evident in early childhood and increased dramatically with age; 26% of adults had microalbuminuria and 24% had overt albuminuria. All renal failure developed out of a background of overt albuminuria. ACR was significantly correlated with the presence of scabies at screening, with a history of poststreptococcal glomerulonephritis, which is epidemic and endemic in the community, with increasing body wt, blood pressure, glucose, insulin and lipid levels, and with evidence of heavy drinking. ACR was also significantly and inversely correlated with birth weight. As a result of its association with deteriorating hemodynamic and metabolic profiles, increasing ACR was also correlated with increasing cardiovascular risk score. Direct observations showed, and multivariate models predicted, progressive amplification of ACR when multiple risk factors were present simultaneously. Albuminuria also clustered in families. CONCLUSION: Renal disease in this population is multifactorial, with risk factors related to whole-of-life nutrition, metabolic and hemodynamic profiles, infections, health behaviors, and possibly a family predisposition. Its relationship to low birth weight, and its associations with deteriorating metabolic and hemodynamic profiles, suggest that renal disease is, in part, a component of Syndrome X, which explains the simultaneous increase in metabolic, cardiovascular and renal disease in Aboriginal people. The family clustering might have both environmental and genetic causes, and is under further investigation. Most of the identified risk factors arise out of poverty, disadvantage and accelerated lifestyle change, and the current epidemic can be explained by the confluence of many risk factors in the last few decades. The introduction of effective and sustained programs to address social, economic and educational inequities in all Aboriginal communities, and of screening and renal- and cardiovascular-protective treatment programs for those already afflicted are matters of great urgency.

Adolescent

Low genetic diversity of Haemophilus influenzae type b compared to nonencapsulated H. influenzae in a population in which H. influenzae is highly endemic.

Immunization with Haemophilus influenzae type b (Hib) conjugate polysaccharide vaccines has dramatically reduced Hib disease worldwide. As in other populations, nasopharyngeal carriage of Hib declined markedly in Aboriginal infants following vaccination, although carriage has not been entirely eliminated. In this study, we describe the genetic characteristics and the carriage dynamics of longitudinal isolates of Hib, characterized by using several typing methods. In addition, carriage rates of nonencapsulated H. influenzae (NCHi) are high, and concurrent colonization with Hib and NCHi is common; we also observed NCHi isolates which were genetically similar to Hib. There is a continuing need to promote Hib immunization and monitor H. influenzae carriage in populations in which the organism is highly endemic, not least because of the possibility of genetic exchange between Hib and NCHi strains in such populations.

Amoxicillin

Exposure to dioxin and nonneoplastic mortality in the expanded IARC international cohort study of phenoxy herbicide and chlorophenol production workers and sprayers.

The authors studied noncancer mortality among phenoxyacid herbicide and chlorophenol production workers and sprayers included in an international study comprising 36 cohorts from 12 countries followed from 1939 to 1992. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin or higher chlorinated dioxins (TCDD/HCD) was discerned from job records and company questionnaires with validation by biologic and environmental measures. Standard mortality ratio analyses suggested a moderate healthy worker effect for all circulatory diseases, especially ischemic heart disease, among both those exposed and those not exposed to TCDD/HCD. In Poisson regression analyses, exposure to TCDD/HCD was not associated with increased mortality from cerebrovascular disease. However, an increased risk for circulatory disease, especially ischemic heart disease (rate ratio [RR] 1.67, 95% confidence interval [Cl] 1.23-2.26) and possibly diabetes (RR 2.25, 95% Cl 0.53-9.50), was present among TCDD/HCD-exposed workers. Risks tended to be higher 10 to 19 years after first exposure and for those exposed for a duration of 10 to 19 years. Mortality from suicide was comparable to that for the general population for all workers exposed to herbicides or chlorophenols and was associated with short latency and duration of exposure. More refined investigations of the ischemic heart disease and TCDD/HCD exposure association are warranted.

Adult

A factor analysis of associations among self-reported immune related symptoms in a large twin sample.

We examined the cumulative prevalences of 22 symptoms thought to reflect immune system function reported in a questionnaire mailed to 7616 Australian twins. The associations between symptoms and demographic variables were expressed in terms of polychoric or polyserial correlations, and a principal components analysis performed. Factors representing underlying propensities respectively to allergic disease, various minor infections, diseases associated with aging such as arthritis, skin disease, and respiratory tract infection were extracted. Possible processes underlying these symptom clusters and the relative strengths and weaknesses of this type of analysis are discussed.

Adult

Cancer mortality in workers exposed to phenoxy herbicides, chlorophenols, and dioxins. An expanded and updated international cohort study.

The authors examined cancer mortality in a historical cohort study of 21,863 male and female workers in 36 cohorts exposed to phenoxy herbicides, chlorophenols, and dioxins in 12 countries. Subjects in this updated and expanded multinational study coordinated by the International Agency for Research on Cancer were followed from 1939 to 1992. Exposure was reconstructed using job records, company exposure questionnaires, and serum and adipose tissue dioxin levels. Among workers exposed to phenoxy herbicides contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or higher chlorinated dioxins, mortality from soft-tissue sarcoma (6 deaths; standardized mortality ratio (SMR) = 2.03, 95% confidence interval (CI) 0.75-4.43) was higher than expected from national mortality rates. Mortality from all malignant neoplasms (710 deaths; SMR = 1.12, 95% CI 1.04-1.21), non-Hodgkin's lymphoma (24 deaths; SMR = 1.39, 95% CI 0.89-2.06), and lung cancer (225 deaths; SMR = 1.12, 95% CI 0.98-1.28) was slightly elevated. Risks for all neoplasms, for sarcomas, and for lymphomas increased with time since first exposure. In workers exposed to phenoxy herbicides with minimal or no contamination by TCDD and higher chlorinated dioxins, mortality from all neoplasms (398 deaths; SMR = 0.96, 95% CI 0.87-1.06), non-Hodgkin's lymphoma (9 deaths; SMR = 1.00), and lung cancer (148 deaths; SMR = 1.03) was similar to that expected, and mortality from soft-tissue sarcoma was slightly elevated (2 deaths; SMR = 1.35). In a Poisson regression analysis, workers exposed to TCDD or higher chlorinated dioxins had an increased risk for all neoplasms (rate ratio = 1.29, 95% CI 0.94-1.76) compared with workers from the same cohort exposed to phenoxy herbicides and chlorophenols but with minimal or no exposure to TCDD and higher chlorinated dioxins. These findings indicate that exposure to herbicides contaminated with TCDD and higher chlorinated dioxins may be associated with a small increase in overall cancer risk and in risk for specific cancers.

Australia

A prospective study of the impact of community-based azithromycin treatment of trachoma on carriage and resistance of Streptococcus pneumoniae.

In February 1995, single-dose azithromycin was given to children with trachoma and their household contacts who were children. For children with trachoma, rates of carriage of pneumococci immediately before treatment with azithromycin and 2-3 weeks, 2 months, and 6 months after treatment were 68% (54 of 79), 29% (11 of 38), 78% (29 of 37), and 87% (34 of 39), respectively. The proportion of carriage-positive children with azithromycin-resistant Streptococcus pneumoniae strains was 1 of 54 (1.9%) before treatment and then 6 of 11 (54.5%), 10 of 29 (34.5%), and 2 of 34 (5.9%) at follow-up visits. The profile of pneumococcal serotypes changed after azithromycin treatment. Azithromycin-resistant strains (serotypes 10F, 23A, and 45) were isolated from 1 (1.3%) of 79 pretreatment swab specimens, from 16 (21.3%) of 75 swab specimens collected up to 2 months after treatment, and from 2 (6%) of 32 obtained 6 months after treatment. Mathematical modeling showed a more rapid appearance of azithromycin-resistant pneumococcal strains in previously colonized children than in previously noncolonized children. Thus, it appears that the selective effect of azithromycin allowed the growth and transmission of preexisting azithromycin-resistant strains. More research is needed to clarify the clinical relevance and implications of azithromycin use.

Adolescent

Nonencapsulated Haemophilus influenzae in Aboriginal infants with otitis media: prolonged carriage of P2 porin variants and evidence for horizontal P2 gene transfer.

Aboriginal infants in the Northern Territory of Australia experience recurrent otitis media from an early age. Nonencapsulated Haemophilus influenzae (NCHi) colonization of the nasopharynx initially occurs within weeks of birth, persists throughout infancy and most of childhood, and contributes to otitis media. We established previously that the high carriage rates of NCHi in these infants result from concurrent and successive colonization with multiple strains, with sequential elimination of dominant strains. We have now sequenced loops 4, 5, and 6 of the NCHi P2 porin gene and characterized several strains with prolonged carriage times. Furthermore, despite a wide diversity of P2 gene sequences, we have four examples of P2 gene identity for strains with different genetic backgrounds as characterized by PCR ribotyping and randomly amplified polymorphic DNA typing, which leads us to suggest that the P2 gene has been transferred between strains. We also discuss the possibility that the paradoxical observation of cocolonization and prolonged carriage of P2-identical strains is related to immune suppression or tolerance in the host.

Amino Acid Sequence

Carriage of multiple ribotypes of non-encapsulated Haemophilus influenzae in aboriginal infants with otitis media.

Ribotyping with the restriction enzyme XbaI was used to study the dynamics of Carriage of non-encapsulated Haemophilus influenzae (NCHi) in Aboriginal infants at risk of otitis media. Carriage rates of NCHi in the infants in the community were very high; the median age for detection was 50 days and colonization was virtually 100% by 120 days of age and persisted at a high level throughout the first year of life [1]. Eighteen different ribotypes of NCHi were identified from 34 positive swabs taken from 3 infants over a period of 9 months. The same ribotypes were recovered for up to 3 months from consecutive swabs of individual infants, and 12 of 27 swabs (44.4%) yielded two ribotypes from four colonies typed. Statistical analysis suggested that most swabs would have been positive for two ribotypes if enough colonies had been typed although the second most frequent ribotype was detected on average in only 13% of strains. Early colonization and carriage of multiple ribotypes of NCHi may help to explain the chronicity of carriage and thus the persistence of otitis media in Aboriginal infants.

Bacterial Typing Techniques

Markers for cardiovascular and renal morbidity: expectations for an intervention programme in an Australian aboriginal community.

1. Australian Aborigines have high rates of both cardiovascular mortality and renal failure and the usual male dominance in these conditions is respectively reduced and effaced. 2. In one Aboriginal community, we have demonstrated a strong association between albuminuria and cardiovascular risk factors and a relationship of both with insulin resistance, which is more pronounced in females than males. 3. We propose that albuminuria is a component of Syndrome X and that reduction in levels of albuminuria should prove to be a useful marker of effectiveness in treatment programmes targeting cardiovascular risk as well as renal disease.

Albuminuria

Anti-streptokinase antibodies and streptokinase resistance in an Aboriginal population in northern Australia.

BACKGROUND: Thrombolytic treatment with streptokinase in acute myocardial infarction has proven to be safe and effective in Caucasian populations with relatively low levels of anti-streptokinase IgG and streptokinase resistance. Higher levels of antibodies, as seen in previous recipients of streptokinase therapy, cause more adverse reactions and may result in lower efficacy. AIMS: To examine the levels of anti-streptokinase IgG and streptokinase resistance in a population subjected to endemic streptococcal infections. METHODS AND RESULTS: Thirty Aboriginal adults from a remote community in Northern Australia with endemic streptococcal infections and 15 non-Aboriginal adults from an urban community without endemic infections participated in this study. Aboriginal adults exhibited levels of anti-streptokinase IgG and streptokinase resistance that, respectively, were almost 20 and 15 times greater than the values of non-Aboriginal adults. At least 23% of Aboriginal adults had sufficiently high levels of streptokinase resistance to neutralise a standard 1.5 million unit dose of streptokinase. CONCLUSIONS: Aboriginal adults from a remote community had dramatically elevated levels of anti-streptokinase IgG and in vitro streptokinase resistance. Prospective studies are needed to assess the clinical relevance of streptokinase resistance in populations from areas with endemic streptococcal infection.

Adult

Sustainability of a successful health and nutrition program in a remote aboriginal community.

OBJECTIVE: To assess the long term effect of a nutrition program in a remote Aboriginal community (Minjilang). DESIGN: Evaluation of nutritional outcomes over the three years before and the three years after a health and nutrition program that ran from June 1989 to June 1990. Turnover of food items at the community store was used as a measure of dietary intake at Minjilang and a comparison community. SETTING: A community of about 150 Aboriginal people live at Minjilang on Croker Island, 240 km north-east of Darwin. A similar community of about 300 people on another island was used as the comparison. RESULTS: The program produced lasting improvements in dietary intake of most target foods (including fruit, vegetables and wholegrain bread) and nutrients (including folate, ascorbic acid and thiamine). Sugar intake fell in both communities before the program, but the additional decrease in sugar consumption during the program at Minjilang "rebounded" in the next year. Dietary improvements in the comparison community were delayed and smaller than at Minjilang. CONCLUSIONS: The success of the program at Minjilang was linked to an ongoing process of social change, which in turn provided a stimulus for dietary improvement in the comparison community. When Aboriginal people themselves control and maintain ownership of community-based intervention programs, nutritional improvements can be initiated and sustained.

Diet

Vir typing: a long-PCR typing method for group A streptococci.

We have developed a new procedure (Vir typing) for typing Streptococcus pyogenes, by amplifying the entire 5- to 7-kb variable vir regulon by long PCR. The amplified DNA is then cleaved with HaeIII and visualized by ethidium bromide fluorescence after agarose gel electrophoresis. A simple procedure for preparing DNA of sufficiently high quality from 96 samples was employed simultaneously. This DNA was also used to develop a random amplified polymorphic DNA (RAPD) procedure. The discriminatory power of the two DNA-based procedures was compared with previous methods, M typing, and multilocus enzyme electrophoresis. Both procedures were highly discriminatory, but the stoichiometric yield of restriction fragments in Vir typing allows unambiguous interpretation of results.

Bacterial Proteins

Long PCR-ribotyping of nontypeable Haemophilus influenzae.

PCR-ribotyping, a new typing method based on long PCR, has been developed for nontypeable Haemophilus influenzae (NTHi). Ribosomal operons of NTHi were amplified by long PCR and were found to be highly polymorphic for internal HaeIII sites. The technique was applied to 49 isolates previously subjected to conventional ribotyping, and the two methods showed a high level of concordance for serial isolates from individual subjects. PCR-ribotyping provides a powerful new typing tool for strain characterization in epidemiological investigations of NTHi.

Bacterial Typing Techniques

Multiple strains of Streptococcus pyogenes in skin sores of aboriginal Australians.

A molecular technique (random amplification of polymorphic DNA) was used to characterize group A streptococcal (GAS) strains among 194 isolates from 55 swabs from 12 Australian Aboriginal children and adults with multiple pyoderma lesions. Ninety-three percent of the lesions contained only one strain of GAS, but 8 of 12 individuals were infected with more than one strain. We conclude that accurate epidemiologic surveys require that more than one swab specimen be obtained from each person, whereas typing of more than one colony per swab is less informative. Characterization of GAS strains by random amplification of polymorphic DNA analysis should help to provide important insights into the epidemiology of GAS, particularly in tropical populations where many isolates are M nontypeable, and into the mechanisms of genetic variation of GAS in such populations.

Adult