Overlying urostomy bag simulating urinary leak in a postrenal transplant MAG3 study.
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Equipment Failure↗
Biomedical subjects
R Hussain
Publications and source records attributed to R Hussain.
Elevated serum CCL2 concomitant with a reduced mycobacterium-induced response leads to disease dissemination in leprosy.
Mycobacterium leprae and Mycobacterium tuberculosis are successful intracellular pathogens which down regulate host immune responses. T-cell interferon-gamma (IFNgamma) and macrophage tumour necrosis factor-alpha (TNFalpha) activate chemokines such as, C-C chemokine ligand-2 (CCL2) and CCL5, which play a role in granuloma formation. Lepromatous leprosy is characterized by defective granulomas with lowered T-cell- and macrophage-mediated responses. Tuberculosis (TB) can be localized to the lung, whereby discreet granulomas are formed. The role of chemokines in leprosy infections is as yet unclear. We compared chemokine responses in lepromatous leprosy and pulmonary tuberculosis patients. Circulating serum CCL2 was raised while CCL5 was lowered in leprosy, as compared with TB patients and healthy controls. However, both Mycobacterium bovis BCG- (P=0.08) and M. leprae-induced (P=0.05) CCL2 secretion was reduced in leprosy. In leprosy, BCG induced greater CCL2 (P=0.01), TNFalpha (P=0.02) and somewhat greater CCL5 (P=0.08) than M. leprae, while CXCL8 induction was comparable. Overall levels of Mycobacterium-induced CCL2, TNFalpha and CXCL8 were two to threefold lower, and CCL5 was 10-fold lower in leprosy as compared with TB. Reduced inducible CCL2 combined with a lowered TNFalpha response in lepromatous leprosy may contribute to the unrestricted growth and dissemination of mycobacteria found in the disease.
Adult↗
An assessment of intellectual disability among Aboriginal Australians.
BACKGROUND: The health and well-being of Indigenous people is a significant global problem, and Aboriginal Australians suffer from a considerably higher burden of disease and lower life expectancy than the non-Indigenous population. Intellectual disability (ID) can further compromise health, but there is little information that documents the prevalence of ID among indigenous populations. This study provides information on ID among the Aboriginal population of Western Australia. METHODS: The Disability Services Commission (DSC) of Western Australia has maintained a statewide database of people with ID since 1953. Data on people of Aboriginal descent were extracted from the DSC database and linked to two other state-based databases, the Hospital Morbidity Data System and the Deaths Registry, with additional linkage to the National Death Index. The linked data were used to assess the prevalence, survival patterns and causes of death in Aboriginal people with ID. RESULTS: Although comprising 3.5% of the population, Aboriginal Australians represented 7.4% of all people registered for ID services. The level of ID was assessed as borderline or mild in 40.7% of cases, moderate in 19.9%, severe or profound in 12.1%, but had not been specified in 27.2% cases. Median survival was 55.1 years for men and 64.0 years for women, with a mean age at death (n = 102) of 19.6 years. The leading causes of death were respiratory diseases, diseases of the circulatory system, and accidents. CONCLUSIONS: The study presents unique population summary data for ID in the Aboriginal community of Western Australia. To provide appropriate prevention and intervention strategies, there is an urgent need for more detailed information on the prevalence and patterns of ID.
Adolescent↗
Rapid immunochromatography-based detection of mixed-species malaria infection in Pakistan.
We report the identification of mixed Plasmodium infections in four recent patients with malaria clinically refractory to empiric chloroquine therapy using the rapid antigen detection kit, NOW ICT Malaria Pf/Pv. A rapid in vitro immunodiagnostic test, the NOW ICT Malaria Pf/Pv test kit was used for the detection of circulating Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) antigens in whole blood. Peripheral blood microscopy confirmed mixed-species infection in all the cases. Thick and thin peripheral blood films were made and stained with Giemsa stain and examined by both hospital laboratory staff and an experienced parasitologist who was blinded to the results of the rapid malarial antigen tests. Four recent patients (all male; mean age, 24 years) with mixed malarial infection were identified. All the subjects were males working for an oil company in a coastal area of Pakistan, and all had been diagnosed presumptively with malaria based on clinical grounds (without microbiologic confirmation), and were treated empirically with chloroquine without clinical response. Semiquantitative malaria counts via microscopy were as follows: P. vivax, scanty (2 patients) and moderate (2 patients); for P. falciparum--scanty (1 patient), moderate (2 patients), and heavy (1 patient). The present case series, although limited by the small number of patients with proven mixed P. falciparum-P. vivax infection, highlights the usefulness of the rapid antigen test in a highly malarious region of Pakistan where chloroquine resistance is prevalent. Although there was full concordance between the results of blood smear microscopy and rapid antigen testing, these techniques are potentially most useful when there is a discrepancy with microscopy findings. Accurate and rapid diagnosis of parasites, particularly in cases of mixed P. falciparum and P. vivax infection, is of immense importance for individual patient management and in reducing the burden of disease, especially in regions of chloroquine resistance.
Adult↗
An experimental model for amoebic abscess production in the cheek pouch of the Syrian golden hamster, Mesocricetus auratus.
A new experimental model was developed in hamsters for amoebic abscess caused by Entamoeba histolytica. E. histolytica trophozoites were cultured in a liquid axenic medium, and then injected intradermally into the cheek pouch of the Syrian golden hamster, Mesocricetus auratus. Inoculation consistently resulted in abscess formation at the site in 20 of 22 (91%) study animals. The amoebic nature of the abscesses was confirmed by light microscopy and histopathologic examination. Abscess formation was maximal at day 12 post-inoculation. Potential applications of this simple and reliable model include further elucidation of the pathogenesis of invasive amoebiasis, studies of the host response to amoebae, and in vivo evaluation of chemotherapeutic agents that show in vitro efficacy against E. histolytica.
Amebiasis↗
IgG1 antimycobacterial antibodies can reverse the inhibitory effect of pentoxifylline on tumour necrosis factor alpha (TNF-alpha) secreted by mycobacterial antigen-stimulated adherent cells.
Chronic inflammation associated with cachexia, weight loss, fever and arthralgia is the hallmark of advanced mycobacterial diseases. These symptoms are attributed to the chronic stimulation of tumour necrosis factor (TNF)-alpha. Mycobacterial components directly stimulate adherent cells to secrete TNF-alpha. We have shown recently that IgG1 antimycobacterial antibodies play a role in augmenting TNF-alpha in purified protein derivative (PPD)-stimulated adherent cells from non-BCG-vaccinated donors. We now show that IgG1 antibodies can also augment TNF-alpha expression in stimulated adherent cells obtained from BCG-vaccinated donors and this augmentation is not linked to interleukin (IL)-10 secretion. In addition IgG1 antimycobacterial antibodies can reverse the effect of TNF-alpha blockers such as pentoxifylline and thalidomide. These studies therefore have clinical implications for anti-inflammatory drug treatments which are used increasingly to alleviate symptoms associated with chronic inflammation.
Adult↗
Leprosy patients with lepromatous disease have an up-regulated IL-8 response that is unlinked to TNF-alpha responses.
Tumor necrosis factor (TNF-alpha) in conjunction with interferon-gamma (IFN-gamma) plays an important role in lymphocyte recruitment and granuloma formation in mycobacterial diseases. Lepromatous leprosy infections are typically associated with low to absent T cell responses and the absence of INF-gamma secretion. Chemokines such as IL-8, MCP-1, and MIP-1beta, have also been shown to recruit neutrophils and lymphocytes to the site of mycobacterial infections. We have studied IL-8 expression in relation to TNF-alpha and TGF-beta in monocytes from lepromatous patients (LL) as compared with healthy endemic controls. In endemic controls, no spontaneous expression of IL-8, TNF-alpha, and TGF-beta was observed, but BCG and M. leprae induced activation of all three cytokines. Lepromatous leprosy monocytes spontaneously expressed high levels of IL-8 and TGF-beta but negligible levels of TNF-alpha. A further increase in IL-8 secretion or gene expression by BCG or M. leprae was not significant. BCG, but not M. leprae, was able to stimulate TNF-alpha activation in lepromatous leprosy subjects. TGF-beta responses in LL were parallel to those of IL-8. This suggests a vigorous and active ongoing IL-8 response in lepromatous disease that is independent of TNF-alpha activation. Therefore, in the absence of IFN-gamma and TNF-alpha activation, IL-8 may assume a pivotal role in cell recruitment in leprosy patients with disseminated mycobacterial infections.
Adult↗
Localization of upper GI bleed on delayed imaging with 99mTc tagged RBC angiogram.
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Aged↗
Breast cancer and the uptake of mammography screening services by women with intellectual disabilities.
BACKGROUND: It is estimated that approximately 50% of women in Australia with intellectual disability will live to 70 years of age and as a result many will fall within the age group at highest risk for breast cancer (50-69 years). METHODS: Subjects were identified through the Western Australia Disability Services database. To determine the number of women diagnosed with breast cancer during the period 1982-2000, individual records (n = 2,370) were linked to the Western Australia Cancer Registry and the Mammography Screening Registry. RESULTS: The incidence of breast cancer among women with intellectual disability was 64.0 per 100,000 person-years, by comparison with 146.7 per 100,000 person-years in the general population. The uptake of breast cancer screening was examined in a subgroup of 380 women, 34.7% of whom had used mammographic screening, as opposed to 54.6% screening uptake in the general population. Failure to use screening services was highest in women who were unmarried, and was positively associated with severity of intellectual disability, presence of physical disabilities, and urban residence. CONCLUSIONS: The lower incidence of breast cancer in women with intellectual disability may in part be attributable to decreased life expectancy, but it also appears to reflect significant under utilization of the readily available screening services.
Activities of Daily Living↗
The effect of mycobacterial virulence and viability on MAP kinase signalling and TNF alpha production by human monocytes.
SETTING: The success of Mycobacterium tuberculosis as a human pathogen depends on its ability to tolerate and perhaps manipulate host defense mechanisms. OBJECTIVE: To determine the induction of tumour necrosis factor-alpha (TNF alpha), a central mediator of immunity, by human monocytes infected with virulent M. tuberculosis, M. leprae and attenuated M. bovis BCG. DESIGN: Mycobacteria-induced cellular activation pathways of TNF alpha production was investigated using an inhibitor of protein tyrosine kinase (PTKs) and an inhibitor of mitogen-activated protein (MAP) kinases. RESULTS: TNF alpha production was significantly lower during infection with virulent M. tuberculosis than with BCG and this differential response was independent of mycobacterial viability. TNF alpha production involved the PTK and MAP kinase pathways. Reduced TNF alpha induction by M. tuberculosis was associated with a reduction in the extent and duration of phosphorylation of extracellular-signal regulated kinases (ERK 1/2). Infection with M. leprae triggered low and transient ERK 1/2 activation as well as low TNF alpha production. CONCLUSION: Maintenance of the differential response in both live and heat-killed preparations suggests that the reduced TNF alpha response associated with virulent mycobacteria is due to differences in the presence of components capable of triggering host pattern recognition receptors, rather than events associated with phagosome trafficking or the active release of intracellular modulators.
BCG Vaccine↗
The changing survival profile of people with Down's syndrome: implications for genetic counselling.
Cohort studies have indicated that the survival of individuals with Down's syndrome has dramatically increased over the past 50 years. Early childhood survival in particular has shown major improvement, due largely to advances in cardiac surgery and in general health management. The present study was based on a continuous cohort of 1332 people with Down's syndrome in Western Australia, registered for intellectual disability services between 1953 and 2000. Their life expectancy was 58.6 years, 25% lived to 62.9 years, and the oldest living person is 73 years of age. Life expectancy for males was greater than females by 3.3 years. The substantial increase in survival across the study period means that the life expectancy of people with Down's syndrome is approaching that of the general population, but accompanied by a range of significant mid-life health problems. The findings are of relevance to all developed countries and have considerable implications in terms of the counselling information provided to families at risk of having a child with Down's syndrome.
Cohort Studies↗
Human T cell responses to peptides of the Mycobacterium leprae 45-kD serine-rich antigen.
In order to identify T cell epitopes within the Mycobacterium leprae 45-kD serine-rich antigen, we analysed responses to overlapping 17-mer peptides encompassing the whole antigen in non-exposed UK controls, Pakistani leprosy patients and tuberculosis patients in both the United Kingdom and Pakistan. This antigen has been described as M. leprae-specific, although it has a hypothetical homologue in M. tuberculosis. Human peripheral blood mononuclear cells were stimulated with peptide for 5 days and IFN-gamma measured in supernatants by ELISA. Some peptides were recognized more frequently by T cells from tuberculoid leprosy patients than those from UK controls, suggesting that such T cell epitopes might have diagnostic potential, while other peptides induced greater responses among UK control subjects. Short-term cell lines confirmed that these assays detected specific T cell recognition of these peptides. However, many tuberculosis patients also recognized these potentially specific peptides suggesting that there could be a true homologue present in M. tuberculosis.
Amino Acid Sequence↗
The influence of intellectual disability on life expectancy.
BACKGROUND: To date, relatively few representative data have been available to health planners and advocacy groups on the life expectancy of people with intellectual disability. A study of trends in the survival profiles of people with intellectual disability was undertaken to assist in the planning of appropriate medical and support services. METHODS: Since 1953, the Disability Services Commission of Western Australia has maintained a database of persons diagnosed with intellectual disability. The database was used to calculate survival probabilities on a total of 8724 individuals, 7562 of whom were still alive at the time of sampling in December 2000. RESULTS: Kaplan-Meier survival plots showed a strong negative association between severity of intellectual disability and survival, with median life expectancies of 74.0, 67.6, and 58.6 years for people with mild, moderate, and severe levels of handicap. Significant negative associations also were observed with male gender, Indigenous Australian parentage, and individuals diagnosed with a specific genetic disorder. CONCLUSIONS: The findings indicate a major and expanding increase in the service requirements of this aging, intellectually disabled population during the past two generations.
Adult↗
Risk factors for neonatal mortality in low-income population subgroups in Karachi, Pakistan.
This paper assesses the risk factors for neonatal mortality (0-28 days of life) for full-term singleton live births. The study sample comprised 1,011 ever-married women who were residents of four multi-ethnic, multi-religious low-income areas of Karachi, Pakistan during 1995. The analysis sample was restricted to 4,488 live births to 912 women. Results showed that 4.8% (n = 217) of all births ended in death in the neonatal period, and 76% (n = 164) of these neonatal deaths occurred in the first week of life. While neonatal mortality rates had declined appreciably over time, a large proportion of neonatal deaths were clustered in a small group of women. The univariate analysis showed a statistically significant association between a number of maternal-level parameters (e.g., mother's age at birth, level of formal education, employment status, religious affiliation, and consanguinity) and child-level parameters (e.g., birth order, birth interval, survival status of the preceding child, sex of the neonate, year of death). At the multivariate level, consanguinity, birth order and year of death were found to be statistically significant risk factors for neonatal mortality analyses despite adjustment for death clustering. The study highlights the importance of inbreeding as a determinant of early offspring death, and points to the need for better understanding of why deaths are clustered in certain families. Given the widespread practice of close cousin marriages in Pakistan across all socio-economic groups, there is a need to validate the findings in less economically disadvantaged population subgroups within the country.
Journal Article↗
Cerebral involvement in benign tertian malaria.
Although Plasmodium vivax usually causes benign uncomplicated malaria, it can occasionally result in severe disease with life-threatening, end-organ involvement generally seen with falciparum malaria. We report a case of cerebral malaria caused by P. vivax and review the literature on this subject.
Electrophoresis, Agar Gel↗
Effect of the disulfide bridge and the C-terminal extension on the oligomerization of the amyloid peptide ABri implicated in familial British dementia.
Familial British dementia (FBD) is a rare neurodegenerative disorder and shares features with Alzheimer's disease, including amyloid plaque deposits, neurofibrillary tangles, neuronal loss, and progressive dementia. Immunohistochemical and biochemical analysis of plaques and vascular amyloid of FBD brains revealed that a 4 kDa peptide named ABri is the main component of the highly insoluble amyloid deposits. In FBD patients, the ABri peptide is produced as a result of a point mutation in the usual stop codon of the BRI gene. This mutation produces a BRI precursor protein 11 amino acids longer than the wild-type protein. Mutant and wild-type precursor proteins both undergo furin cleavage between residues 243 and 244, producing a peptide of 34 amino acids in the case of ABri and 23 amino acids in the case of the wild-type (WT) peptide. Here we demonstrate that the intramolecular disulfide bond in ABri and the C-terminal extension are required to elongate initially formed dimers to oligomers and fibrils. In contrast, the shorter WT peptide did not aggregate under the same conditions. Conformational analyses indicate that the disulfide bond and the C-terminal extension of ABri are required for the formation of beta-sheet structure. Soluble nonfibrillar ABri oligomers were observed prior to the appearance of mature fibrils. A molecular model of ABri containing three beta-strands, and two beta-hairpins annealed by a disulfide bond, has been constructed, and predicts a hydrophobic surface which is instrumental in promoting oligomerization.
Adaptor Proteins, Signal Transducing↗
Opsonizing antibodies (IgG1) up-regulate monocyte proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and IL-6 but not anti-inflammatory cytokine IL-10 in mycobacterial antigen-stimulated monocytes-implications for pathogenesis.
Cachexia is one of the prominent features of advanced tuberculosis (TB) seen in association with increased expression of the monokine TNF-alpha. Several mycobacterial proteins, including PPD, stimulate TNF-alpha secretion from monocytes. Host factors that may play a role in cytokine expression from monocytes remain largely unknown. One such factor is the opsonizing antibodies. Monocytes have high-affinity receptors (FcgammaI and FcgammaIII) for IgG1 and IgG3 antibodies that mediate antigen uptake. We have reported selective up-regulation of IgG1 (which bind to Fcgamma receptors) in advanced TB and have recently shown the ability of PPD-specific IgG1 antibodies to augment TNF-alpha expression in PPD-stimulated monocytes. These observations have now been extended to other cytokines with semipurified fractions from secreted antigens of Mycobacterium tuberculosis (containing 30 kD and 58 kD) that were devoid of lipids, glycolipids and carbohydrates. In the presence of heat-inactivated TB plasma containing known amounts of antigen-specific IgG1 antibodies, these fractions induced significantly increased TNF-alpha, IL-6 and IL-10 secretion. Absorption of IgG1 with Protein 'A' removed the augmenting activity for TNF-alpha and IL-6 secretion from the TB plasma samples. In the case of IL-10, removal of IgG1 resulted in increased rather than decreased IL-10 secretion. These results suggest a possible pathogenic role for antibodies in TB by enhancing proinflammatory and blocking down-regulatory cytokines such as IL-10 cytokines during the chronic phase of TB.
Antigens, Bacterial↗
Treatment of tibial diaphyseal fractures with closed flexible intramedullary ender nails: 39 fractures followed for a period of two to seven years.
OBJECTIVE: To assess the efficacy of flexible intramedullary Ender nails for the treatment of tibial diaphyseal. MATERIALS AND METHODS: This is a retrospective review of patients treated with the Ender Nail for both open and closed tibial shaft fractures. Between January 1989 and December 1994, 43 fractures were treated with these nails. The configuration of each fracture was determined using the Orthopedic Trauma Association classification and the extent of soft tissue damage was assessed using the Gustilo and Anderson's classification. Four patients were excluded from the study due to inadequate follow-up. There were 27 closed and 12 open fractures. RESULTS: The average time to union in 34 out of 39 fractures was 17 weeks. Delayed union and malunion occurred in two patients each and superficial wound infection in 1 patient. Nonunion occurred in 5 fractures that were all located in the distal 1/3 of the tibial diaphysis. We attribute this high rate of non-union to a poor rotational control on the distal fragment by these nails. CONCLUSIONS: The Ender nails provide effective fixation for the OTA stable class of tibial fractures, where they produce good axial and rotational stability by virtue of their three-point fixation. Rotational and angular stability should be improved by a supplementary cast immobilization for fractures with unstable configuration and those located in the distal third of the diaphysis.
Adolescent↗