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Biomedical subjects

A Elliott

Publications and source records attributed to A Elliott.

At least 19 recordsLinked to original sources

Operational assessment of isoniazid prophylaxis in a community AIDS service organisation in Uganda.

SETTING: Isoniazid therapy was shown to be 70% effective at preventing tuberculosis in HIV-infected, PPD-positive Ugandan adults, but the feasibility of implementation outside an efficacy trial has not been established. OBJECTIVE: To study uptake, adherence and feasibility of a 6-month course of isoniazid preventive therapy in community-based HIV clinics in Uganda. DESIGN: Observational cohort study describing selection of patients and adherence to isoniazid 300 mg daily. Adherence was measured by clinic attendance, pill counts and urine isoniazid metabolite testing. Implementation was costed on a service delivery basis. RESULTS: Of 1597 cohort members, 22% were PPD-positive. Over 18 months, 193 PPD-positive individuals were assessed for prophylaxis and 98 (51%) were enrolled. Of those enrolled, 74 (76%) completed their course of isoniazid therapy, and 80% were fully adherent. Symptoms or previous treatment for tuberculosis and suspicion of tuberculous lymphadenopathy were the main reasons for exclusion. The additional cost of providing this service was US $14,549. CONCLUSION: Clinics specialising in the care of persons with HIV/AIDS can successfully implement isoniazid prophylaxis. Difficulties in excluding active tuberculosis and the costs of running the programme may limit its widespread implementation.

AIDS-Related Opportunistic Infections↗

Epithelial barrier function and ultrastructure of gelatinous drop-like corneal dystrophy.

PURPOSE: Recently, mutations in the M1S1 gene have been identified as responsible for gelatinous drop-like corneal dystrophy (GDLD). How the abnormal M1S1 gene product causes GDLD is not known, although evidence suggests that it may compromise corneal epithelial function. This investigation attempted to determine the effect of the abnormal M1S1 gene product by assessing epithelial barrier function and epithelial ultrastructure in GDLD corneas. METHODS: Epithelial barrier function was assessed on the basis of fluorescein uptake. The method used a modified slit-lamp fluorophotometer. High-resolution scanning electron and atomic force microscopy was used to investigate the amyloid deposits and epithelial cell structure. RESULTS: Epithelial permeability was orders of magnitude higher in GDLD corneas than normal. The structure of the amyloid deposits was characterized, and clear abnormalities in epithelial morphology and cell junctions were observed. CONCLUSIONS: The high epithelial permeability observed in GDLD corneas was directly correlated with abnormalities in epithelial structure, including irregular cell junctions. This suggests that the abnormal M1S1 gene product may affect epithelial cell junctions resulting in increased cell permeability in GDLD corneas.

Adult↗

Reversal of dysthyroid optic neuropathy following orbital fat decompression.

AIMS: To document the successful treatment of five patients with dysthyroid optic neuropathy by orbital fat decompression instead of orbital bone decompression after failed medical therapy. METHODS: Eight orbits of five patients with dysthyroid optic neuropathy were selected for orbital fat decompression as an alternative to bone removal decompression. Treatment with systemic corticosteroids and/or orbital radiotherapy was either unsuccessful or contraindicated in each case. All patients satisfied clinical indications for orbital bone decompression to reverse the optic neuropathy. High resolution computerised tomographic (CT) scans were performed in all cases and in each case showed signs of enlargement of the orbital fat compartment. As an alternative to bone decompression, orbital fat decompression was performed on all eight orbits. RESULTS: Orbital fat decompression was performed on five patients (eight orbits) with optic neuropathy. Optic neuropathy was reversed in all cases. There were no cases of postoperative diplopia, enophthalmos, globe ptosis, or anaesthesia. All patients were followed for a minimum of 1 year. CONCLUSIONS: In a subset of patients with an enlarged orbital fat compartment and in whom extraocular muscle enlargement is not the solitary cause of optic neuropathy, fat decompression is a surgical alternative to bony decompression.

Adipose Tissue↗

Fine localization of the Nijmegen breakage syndrome gene to 8q21: evidence for a common founder haplotype.

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, a birdlike face, growth retardation, immunodeficiency, lack of secondary sex characteristics in females, and increased incidence of lymphoid cancers. NBS cells display a phenotype similar to that of cells from ataxia-telangiectasia patients, including chromosomal instability, radiation sensitivity, and aberrant cell-cycle-checkpoint control following exposure to ionizing radiation. A recent study reported genetic linkage of NBS to human chromosome 8q21, with strong linkage disequilibrium detected at marker D8S1811 in eastern European NBS families. We collected a geographically diverse group of NBS families and tested them for linkage, using an expanded panel of markers at 8q21. In this article, we report linkage of NBS to 8q21 in 6/7 of these families, with a maximum LOD score of 3.58. Significant linkage disequilibrium was detected for 8/13 markers tested in the 8q21 region, including D8S1811. In order to further localize the gene for NBS, we generated a radiation-hybrid map of markers at 8q21 and constructed haplotypes based on this map. Examination of disease haplotypes segregating in 11 NBS pedigrees revealed recombination events that place the NBS gene between D8S1757 and D8S270. A common founder haplotype was present on 15/18 disease chromosomes from 9/11 NBS families. Inferred (ancestral) recombination events involving this common haplotype suggest that NBS can be localized further, to an interval flanked by markers D8S273 and D8S88.

Chromosome Breakage↗

Low level CO2 effects on pulmonary function in humans.

The purpose of the study was to determine whether chamber exposure to low levels of CO2 results in functional alterations in gas mixing and closing volume in humans. Four healthy volunteer subjects were exposed to 0.7% CO2 and to 1.2% CO2. Spirometry, lung volumes, single breath nitrogen washout, diffusing capacity for carbon monoxide (DLCO) by two methods, and cardiac output were measured in triplicate. Values were obtained over two non-consecutive days during the training period (control) and on days 2 or 3, 4, 6, 10, 13, and 23 of exposure to each CO2 level. Measurements were made during the same time of day. There was one day of testing after exposure, while still in the chamber but off carbon dioxide. The order of testing, up until measurements of DLCO and cardiac output, were randomized to avoid presentation effects. The consistent findings were a reduction in diffusing capacity for carbon monoxide and a fall in cardiac output, occurring to a similar degree with both exposures. For the group as a whole, there was no indication of major effects on spirometry, lung volumes, gas mixing or dead space. We conclude that small changes may occur in the function of distal gas exchanging units; however, these effects were not associated with any adverse health effects. The likelihood of pathophysiologic changes in lung function or structure with 0.7 or 1.2% CO2 exposure for this period of time, is therefore, low.

Breath Tests↗

Intracellular alkalinization mobilizes calcium from agonist-sensitive pools in rat lacrimal acinar cells.

1. We have investigated interactions between intracellular pH (pHi) and the intracellular free calcium concentration ([Ca2+]i) in collagenase-isolated rat lacrimal acinar cells. The fluorescent dyes fura-2 and 2',7'-bis(carboxyethyl)-5-carboxyfluorescein (BCECF) were used to measure [Ca2+]i and pHi, respectively. 2. Application of the weak base NH4Cl alkalinized the cytosol and caused a dose-dependent increase in [Ca2+]i. Trimethylamine (TMA) also alkalinized the cytosol and increased [Ca2+]i. The increase in [Ca2+]i evoked by NH4Cl or TMA was much smaller than that evoked by the secretory agonist acetylcholine (ACh). 3. Application of NH4Cl also increased [Ca2+]i in cells bathed in Ca(2+)-free medium, indicating that NH4Cl released Ca2+ from an intracellular pool. 4. Ammonium chloride had no effect on [Ca2+]i in cells bathed in Ca(2+)-free medium if agonist-sensitive intracellular Ca2+ pools had been depleted with either ACh or the microsomal Ca(2+)-ATPase inhibitor 2,5-di(tert-butyl)hydroquinone. Treatment of cells with NH4Cl in Ca(2+)-free medium reduced the amount of Ca2+ released by ACh. These results suggest that NH4Cl released Ca2+ from the same intracellular pool released by ACh. 5. Calcium release from the agonist-sensitive pool was also triggered when the cytosol was alkalinized by removing the weak acid acetate. 6. Ammonium chloride caused a modest increase in inositol phosphate production, suggesting that NH4Cl may have released stored Ca2+ via an increase in the intracellular inositol 1,4,5-trisphosphate concentration. 7. The increase in [Ca2+]i evoked by NH4Cl was not sustained even in the presence of extracellular Ca2+. In contrast, when a low dose of ACh was used to evoke intracellular Ca2+ release of similar magnitude, sustained Ca2+ entry was observed. 8. Alkalinizing the cytosol appeared to partially inhibit Ca2+ entry triggered by thapsigargin or by ACh. 9. We suggest that alkalinizing the cytoplasm in unstimulated lacrimal acinar cells can release Ca2+ from the intracellular agonist-sensitive Ca2+ pool. However, releasing stored Ca2+ via alkalinization does not appear to trigger significant Ca2+ entry, perhaps because intracellular alkalinization inhibits either the Ca2+ entry pathway or the mechanism which couples the entry pathway to store depletion.

Acetic Acid↗

Vietnamese and Arabic women's responses to the Diagnostic Interview Schedule (depression) and self-report questionnaires: cause for concern.

OBJECTIVE: The original study aimed to determine the best cut-off scores to screen for postnatal depression on translated versions of the Edinburgh Postnatal Depression Scale (EPDS) for Vietnamese and Arabic women. This research was conducted using the depression module of the Diagnostic interview Schedule (DIS) to determine caseness. This paper reports on the suitability of this diagnostic interview as a criterion measure of depression in these women with a non-English speaking background. METHOD: Vietnamese and Arabic women in south-west Sydney completed the EPDS and a General Health Questionnaire (GHQ-30) antenatally. At 6-8 weeks postpartum they completed an EPDS, the GHQ-30 and a Faces Scale, and were interviewed using the depression module of the DIS. Members of a small convenience sample of women were asked about the cultural appropriateness of each of the instruments. RESULTS: Vietnamese women admitted to few depressive symptoms on the DIS, whereas they appeared more open to reporting these on the EPDS and the GHQ-30. Arabic women responded more openly to the questionnaires and the interview, although they too were reluctant to report specific symptoms on the DIS. CONCLUSION: The usefulness of the DIS in determining rates of major depression in the Vietnamese and Arabic community in Australia is questionable. Further studies designed specifically to investigate this are needed.

Adult↗

Personal and family distress in homeless adolescents.

Previous research has indicated that homeless children exhibit high rates of behavioral and emotional problems and come from families characterised by conflict and rejection. Further, some evidence exists to show that family variables may relate to adolescent distress differently for homeless males and females. In this study, 117 homeless adolescents were compared to a sample of non-homeless youths on the self reported incidence of personal and family problems. The homeless children reported the highest incidence of all behavioral and emotional problems, parental marital discord, overprotection, and the lowest levels of parental care and acceptance. Sex effects were not evident in reported levels of personal or family problems. However, substantially more variance in the adolescents level of behavioral and emotional disturbance was predictable from family measures for females than males. Overall, the results point to the importance of incorporating family distress models in the understanding and remediation of adolescent homelessness.

Adolescent↗

Macular detachment following laser treatment for proliferative diabetic retinopathy.

Case records of patients who had macular detachment following argon laser photocoagulation for proliferative diabetic retinopathy were reviewed. Thirteen eyes of 11 patients out of a total of 480 patients treated had this complication, and in 12 eyes of 10 patients the short latency suggested a true precipitating effect. This represents 2.1% of patients receiving panretinal photocoagulation. Patients with detachment were younger and developed diabetes earlier than the controls (P less than 0.025), and the detached eyes had received more numerous laser burns on average per session than the controls (P less than 0.001). In 5 eyes the last photocoagulation dose exceeded 1000 burns delivered in the presence of traction membranes in an attempt to arrest continuing neovascular proliferation not responding to earlier more moderate treatment. Only 1 eye had received early, extensive and repeated photocoagulation. Vigorous treatment at an early stage of the proliferation may prevent this complication, although the advantages or disadvantages of fractionation of photocoagulation will only be shown by a prospective trial.

Adult↗

Impact of human immunodeficiency virus on transmission and severity of tuberculosis.

It is now clear that tuberculosis is one of the major diseases associated with human immunodeficiency virus (HIV) infection and the acquired immune deficiency syndrome both in developing countries and in disadvantaged groups in the northern hemisphere. In the USA, and probably several other countries, the annual incidence of tuberculosis is rising as a result of the HIV epidemic. This is probably a result of an increase in both pulmonary and, especially, extrapulmonary tuberculosis, due to reactivation of latent infections, but a secondary increase in the infection rate is also possible. The hard-won gains in tuberculosis control of the last 30 years are thus in jeopardy. This article focuses on the effect HIV is likely to have on the known risk factors for infection with Mycobacterium tuberculosis and for reactivation. Whilst HIV-associated tuberculosis may be indistinguishable from HIV-negative disease, it is likely in other cases to present diagnostic difficulties, to respond poorly to treatment with more adverse effects, and to result in high early mortality, although this may not be due directly to tuberculosis. HIV-associated tuberculosis thus represents a major challenge to physicians, especially in developing countries, but like other forms of tuberculosis it is (i) treatable and (ii) preventable.

Acquired Immunodeficiency Syndrome↗

The 'catch' mechanism in molluscan muscle: an electron microscopy study of freeze-substituted anterior byssus retractor muscle of Mytilus edulis.

A method for quick-freezing muscles while observing their mechanical properties until the moment of freezing is described. This method was used to freeze the anterior byssus retractor muscle (ABRM) of Mytilus edulis. Intact muscle in the presence of sucrose as a cryoprotectant was freeze-substituted in acetone, fixed and embedded for electron microscopy. ABRM was frozen in a number of mechanical states including 'catch', the state of high passive tension particularly associated with some molluscan muscles. Transverse sections were examined to determine the distribution of filaments in the muscle cells. In the relaxed muscle thick and thin filaments are fairly randomly distributed. Groups of thin filaments and of thick filaments are often seen, and there is no obvious association between the two types of filaments. In contrast, in rigor muscles, both glycerol-extracted and intact, most of the thin filaments were found to lie in rings or rosettes around the thick filaments. In some places bridges between thick and thin filaments could be distinguished. In actively contracting muscle (phasic contraction) the appearance is intermediate between that of the relaxed and rigor muscles. Many thick filaments are surrounded by rosettes of thin filaments but many of the thin filaments are grouped and have no connections with thick filaments. The 'catch' state, left after a period of tonic contraction, is similar in its distribution of thick and thin filaments to the active state, many of the thin filaments lying between the thick. Frequently thick and thin filaments seem to be closer together than in other states of the muscle where a pronounced exclusion zone is present around the thick filaments. There is no evidence for association between the thick filaments. The different distribution of thin filaments in the different states is consistent with the previously described X-ray diffraction data if it is assumed that most of the contribution to the equatorial reflection at 12 nm comes from the groups of thin filaments. Our data support a model for catch in which there is a change in the association between thick and thin filaments, rather than one in which thick filaments are clumped.

Actin Cytoskeleton↗