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B Currie

Publications and source records attributed to B Currie.

At least 55 records · Page 3Linked to original sources
PubMed1995

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↗
PubMed1995

The efficacy of chelation therapy and factors influencing mortality in lead intoxicated petrol sniffers.

BACKGROUND: The use of chelating agents to treat patients with petrol sniffing encephalopathy has been controversial, since alkyllead additives in petrol are not chelatable. A high mortality has also been reported in hospitalised petrol sniffers. AIMS: (i) Evaluate the efficacy of chelating agents in mobilising lead for excretion and lowering blood lead; (ii) Review factors contributing to mortality in hospitalised petrol sniffers. METHODS: All males chelated between 1992-1993 were studied (n = 20). Blood and urinary lead were measured daily before and during chelation then twice weekly until discharge. Parenteral calcium disodium edetate (EDTA) and dimercaprol (BAL) were administered together, every six hours for five days, seven patients subsequently received oral D-penicillamine until discharge. Clinical details were reviewed for eight patients with petrol sniffing encephalopathy who died between 1990-1994. RESULTS: Urinary lead excretion substantially increased during parenteral chelation (median excretion = 113 microM/5 days, compared with pre-chelation excretion = 1.1 microM/day). Median blood lead concentration fell from 4.83 microM/L (pre-chelation) to 1.91 microM/L (post-chelation). D-Penicillamine did not appear to increase urinary lead excretion appreciably. All eight deaths followed sepsis; five from complications of aspiration pneumonia. CONCLUSIONS: Airway maintenance and management are crucial for survival in these patients. In the short-term, parenteral chelation was effective in mobilising lead for excretion and reducing blood lead in encephalopathic petrol sniffers and was comparable to cases of inorganic lead intoxication. However, as in the treatment of inorganic lead intoxication, the long-term efficacy of chelation for petrol sniffers remains controversial. Prevention strategies against petrol sniffing at a community level are recommended.

Chelating Agents↗
PubMed1995

Sterol compositions and susceptibilities to amphotericin B of environmental Cryptococcus neoformans isolates are changed by murine passage.

Previous studies have shown that sequential isolates from patients with persistent Cryptococcus neoformans meningoencephalitis can vary in sterol composition and susceptibility to antifungal drugs. To investigate the potential of host factors as mediators of this phenomenon, we compared fungal susceptibilities of environmental and clinical isolates from a limited geographic area. Clinical isolates were less susceptible to amphotericin B than environmental isolates. Five environmental isolates were passaged through BALB/c murine hosts; the passaged isolates had changes in sterol composition and reduced amphotericin B susceptibilities relative to those of the parent isolates. In contrast, murine passage of these isolates did not alter their susceptibilities to fluconazole. The results confirm that changes in sterol composition and antifungal susceptibility can occur in vivo as a result of host factors and suggest that human infection can result in selection of variants with reduced susceptibilities to amphotericin B.

Amphotericin B↗
PubMed1995

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↗
PubMed1995

Subdivision of Burkholderia pseudomallei ribotypes into multiple types by random amplified polymorphic DNA analysis provides new insights into epidemiology.

Ribotyping has previously been used for epidemiological studies of Burkholderia pseudomallei (previously Pseudomonas pseudomallei). We show here that random amplified polymorphic DNA (RAPD) analysis allows subdivision of strains of the same ribotype. With five different primers, no two epidemiologically unrelated isolates of any single ribotype in this study of 102 isolates from humans, goats, cats, and soil had identical RAPD patterns. Conversely, RAPD analysis showed clonality for isolates from each of two animal outbreaks of melioidosis and from a nontropical focus of animal and human melioidosis spanning 25 years. Some soil isolates were identical to epidemiologically related animal and human isolates as determined by RAPD typing. There was no evidence that the clinical outcome of melioidosis was related to RAPD patterns.

Animals↗
PubMed1994

Towards a vaccine for rheumatic fever: identification of a conserved target epitope on M protein of group A streptococci.

Rheumatic fever and rheumatic heart disease remain very common in developing countries, and a vaccine to protect against these disorders would have a great impact on public health. A vaccine must target the M protein of group A streptococci (Streptococcus pyogenes), but until lately immunity was thought to be strain-specific and dependent on antibodies to the variable serotype-specific regions of the protein. Experiments in animals have suggested the conserved region of the M protein as a possible alternative target for protective antibodies. We constructed a 20-aminoacid peptide (peptide 145) within the conserved region of the carboxyl terminus of the protein. In mice the peptide induced serum antibodies that could opsonise reference type 5 streptococci. By enzyme-linked immunosorbent assay, positive responses to peptide 145 were obtained with serum from 77 (90%) of 86 Aboriginal subjects and 135 (81%) of 167 Thai subjects living in areas with high exposure to streptococci. Only 10 (14%) of 71 Caucasian subjects with low exposure to streptococci showed positive responses. There was no difference in the proportion positive between subjects with rheumatic heart disease and control groups (other or no heart disease). Antibodies to peptide 145 were able to opsonise isolates of streptococci from Aboriginal and Thai subjects with acute rheumatic fever as well as reference strains. This highly conserved part of the M protein may be a suitable target for vaccines to prevent streptococcal infections and their sequelae.

Amino Acid Sequence↗
PubMed1994

Clinical implications of research on the box-jellyfish Chironex fleckeri.

Despite several decades of laboratory research, many anecdotal clinical publications and successful production of antivenom, the active components of Chironex fleckeri venom and their mechanisms of toxicity remain poorly elucidated. Conflicting results of animal experiments and venom studies and the lack of controlled clinical trials necessitate caution in formulating protocols of clinical management. Of particular note are that in severe envenomation (1) clinical deterioration can occur within minutes and cardiac support must be emphasised in addition to respiratory support; (2) larger doses of antivenom may be appropriate; and (3) recommendations of therapy with verapamil and other cardioactive drugs remain controversial.

Animals↗
PubMed1994

Pseudomonas pseudomallei isolates collected over 25 years from a non-tropical endemic focus show clonality on the basis of ribotyping.

Between 1966 and 1991, melioidosis, a disease caused by Pseudomonas pseudomallei that is mostly confined to tropical regions, occurred in farm animals and a farmer in temperate south-west Western Australia. Using an Escherichia coli probe containing a ribosomal RNA operon, P. pseudomallei DNA from isolates from 8 animals, a soil sample and the human case showed an identical ribotype on Southern blotting. The ribotype was different from the 3 commonest ribotypes seen in tropical Australia. This molecular typing supports the theory of clonal introduction of P. pseudomallei into a non-endemic region, with environmental contamination, local dissemination and persistence over 25 years. As melioidosis is often fatal in humans, such persistence in a temperate region is cause for concern.

Animals↗
PubMed1994

Identification of T cell autoepitopes that cross-react with the C-terminal segment of the M protein of group A streptococci.

Rheumatic fever (RF) follows a throat infection with different M-serotypes of beta-hemolytic group A streptococci (GAS) and can affect different tissues, predominantly the heart. It is thought to be an autoimmune illness. Although histological examination of affected heart shows an infiltrate consisting mainly of T cells, antigens or epitopes that could be putative targets of autoimmune T cells have not been identified. We have examined the T cell response to the conserved C-terminal region of the M protein--a streptococcal surface coiled-coil protein which is the target of opsonic antibodies and antibodies which cross-react with human heart tissue. Australian Aborigine, Caucasian and Thai patients, controls and mice were studied to define regions of the protein immunogenic for T cells, and T cell lines and clones were tested for cross-reactivity to myosin as well as an extract of RF-diseased mitral heart valve. Murine (B10, B10.D2, B10.BR) M peptide-specific T cells were often cross-reactive for other M peptides but did not cross-react with human heart antigens. Patients with RF or other heart diseases, or control subjects exposed more commonly to GAS were more likely to have T cell responses to the M protein, with many regions of the C-terminus being recognized. T cell lines and a clone specific for different M peptides were generated from five donors. Cross-reactivity could be shown between different M peptides, but unlike murine M peptide-specific T cells three of the human T cell lines reacted strongly to peptides representing homologous regions of cardiac and skeletal muscle myosins, and two of these lines also responded to porcine myosin and an extract of human rheumatic mitral valve. However, these last two lines were derived from a normal donor without history of RF or other heart disease. Our data demonstrate that regions of the M protein, including regions that are being considered as subunit vaccines, have the potential to stimulate pre-existing heart cross-reactive T cells, but that the ability of such T cells to cross-react (as measured in vitro) is not in itself sufficient to lead to disease.

Adolescent↗
PubMed1994

An unusual presentation of secondary syphilis in the Northern Territory.

OBJECTIVE: To present a case which demonstrates the unusual clinical features of secondary syphilis that may be encountered in tropical Australia. CLINICAL FEATURES: A syphilitic aetiology was initially missed in a Caucasian female presenting with a rare form of syphilis, "lues maligna", characterised by nodulo-ulcerative skin lesions, fever, meningism and a relapsing course. CONCLUSION: Secondary syphilis is usually manifest in the Northern Territory by a characteristic palmo-plantar psoriasiform eruption with variable involvement of skin in other body areas. The disease is most commonly seen in the young adult Aboriginal population. However, atypical presentations can occur and vigilance must be maintained for a syphilitic aetiology in unusual skin lesions. The disease may produce significant individual morbidity and may be transmitted non-venereally to close contacts in the secondary stage. Genital lesions facilitate the transmission of HIV, making early diagnosis and treatment even more important.

Adult↗
PubMed1994

Sterol composition of Cryptococcus neoformans in the presence and absence of fluconazole.

Analysis of the sterol compositions of 13 clinical isolates of the pathogenic yeast Cryptococcus neoformans obtained from five patients with recurring cryptococcal meningitis showed that, unlike Candida albicans, the major sterols synthesized by this yeast were obtusifoliol (range, 21.1 to 68.2%) and ergosterol (range, 0.0 to 46.5%). There was considerable variation in the sterol contents among the 13 isolates, with total sterol contents ranging from 0.31 to 5.9% of dry weight. The isolates from the five patients who had relapses had different total sterol contents and compositions in comparison with those of the pretreatment isolates, indicating either that the sterols had been changed by therapy or that the patients were infected with new isolates with different sterol compositions. Growth of the cryptococcal isolates in the presence of subinhibitory concentrations of fluconazole (0.25x the MIC) significantly altered the sterol content and pattern. The total sterol content decreased in nine isolates and increased in four isolates in response to pretreatment with fluconazole. Fluconazole had no consistent effect on ergosterol levels. In contrast, fluconazole caused a decrease in obtusifoliol levels and an increase in 4,14-dimethylzymosterol levels in all isolates. These results indicate extensive diversity in sterol content, sterol composition, and sterol synthesis in response to subinhibitory concentrations of fluconazole in C. neoformans strains. We propose that fluconazole inhibits the sterol synthesis of C. neoformans by interfering with both 14 alpha-demethylase-dependent and -independent pathways. No correlation between the sterol compositions of C. neoformans isolates and their susceptibilities to fluconazole was found.

Cholestadienols↗
PubMed1993

Strongyloidiasis in the Northern Territory. Under-recognised and under-treated?

OBJECTIVE: To describe the clinical and laboratory features and management of Strongyloides stercoralis infection in the Top End of the Northern Territory. DESIGN: A 12-month retrospective review of clinical records of patients confirmed on stool microscopy to be infected with S. stercoralis. SETTING: The Royal Darwin Hospital (RDH), a 300-bed referral hospital servicing the tropical areas of the Northern Territory, which have a population of 120,000, 21% of which is Aboriginal. RESULTS: Potentially pathogenic gastrointestinal parasites were identified in 205 patients over the 12 months. Of these, 68 patients had strongyloidiasis--64 were Aboriginal, three were Caucasian and one was of New Guinean origin. Thirty-seven (54%) were under five years of age. Patients came from all regions served by RDH, including urban Darwin. Seventy-five per cent of adults had chronic underlying disease and 80% of children under five years old were below 80% of standard weight for age. Gastrointestinal symptoms were absent in 28%; occasionally, severe disease occurred. Eosinophilia with greater than 0.7 x 10(9) cells/L was present in 57% of patients. Only 57% of cases were treated with thiabendazole. CONCLUSION: In the Top End of the Northern Territory, Strongyloides infection is endemic in Aboriginal communities, but also occasionally occurs in non-Aboriginal people. It is likely that the infection is frequently not recognised. Current community-based anthelmintic regimens have succeeded in reducing the prevalence of hookworm infection, but strongyloidiasis still appears to be a prevalent condition. The possibility of hyperinfection or disseminated strongyloidiasis in immunocompromised patients such as renal transplant recipients and people infected with the human immunodeficiency virus needs consideration in this endemic area. The interaction in northern Australia of S. stercoralis with human T-lymphotropic virus type I and with undernutrition warrants further study.

Adolescent↗
PubMed1993

Medicine in tropical Australia.

In the unique environment of Australia's tropical north there are endemic diseases inherited from Gondwana, others introduced from the north and from Europe, and a wide range of particularly venomous animals. There is continuing disparity in morbidity and mortality between Aboriginal people and other Australians in tropical areas and elsewhere. This is being addressed by the National Aboriginal Health Strategy, which emphasises social, environmental and economic issues, as well as control and coordination of services by Aboriginal and Torres Strait Islander communities. While the re-introduction of malaria remains a potential threat, together with other infections, current diseases in tropical Australia are being better elucidated; melioidosis is now recognised as the commonest cause of fatal [corrected] community-acquired pneumonia in the Top End of the Northern Territory, and a new focus of scrub typhus has been found. Sexually transmitted diseases are an urgent issue, especially for Aboriginal communities, given the potential impact of the human immunodeficiency virus.

Animals↗