Who fails to complete tuberculosis treatment? Temporal trends and risk factors for treatment interruption in a community-based directly observed therapy programme in a rural district of South Africa

SETTING: Hlabisa Tuberculosis Programme, Hlabisa, South Africa. OBJECTIVE: To determine trends in and risk factors for interruption of tuberculosis treatment. METHODS: Data were extracted from the control programme database starting in 1991. Temporal trends in treatment interruption are described; independent risk factors for treatment interruption were determined with a multiple logistic regression model, and Kaplan-Meier survival curves for treatment interruption were constructed for patients treated in 1994-1995. RESULTS: Overall 629 of 3610 surviving patients (17%) failed to complete treatment; this proportion increased from 11% (n = 79) in 1991/1992 to 22% (n = 201) in 1996. Independent risk factors for treatment interruption were diagnosis between 1994-1996 compared with 1991-1393 (odds ratio [OR] 1.9, 95% confidence interval [CT] 1.6-2.4); human immunodeficiency virus (HIV) positivity compared with HIV negativity (OR 1.8, 95% CI 1.4-2.4); supervised by village clinic compared with community health worker (OR 1.9, 95% CI 1.4-2.6); and male versus female sex (OR 1.3, 95% CI 1.1-1.6). Few patients interrupted treatment during the first 2 weeks, and the treatment interruption rate thereafter was constant at 1% per 14 days. CONCLUSIONS: Frequency of treatment interruption from this programme has increased recently. The strongest risk factor was year of diagnosis, perhaps reflecting the impact of an increased caseload on programme performance. Ensuring adherence to therapy in communities with a high level of migration remains a challenge even within community-based directly observed therapy programmes.

Assessment of limb muscle and adipose tissue by dual-energy X-ray absorptiometry using magnetic resonance imaging for comparison

OBJECTIVE: To use magnetic resonance imaging (MRI) to validate estimates of muscle and adipose tissue (AT) in lower limb sections obtained by dual-energy X-ray absorptiometry (DXA) modelling. DESIGN: MRI measurements were used as reference for validating limb muscle and AT estimates obtained by DXA models that assume fat-free soft tissue (FFST) comprised mainly muscle: model A accounted for bone hydration only; model B also applied constants for FFST in bone and skin and fat in muscle and AT; model C was as model B but allowing for variable fat in muscle and AT. SUBJECTS: Healthy men (n = 8) and women (n = 8), ages 41 - 62 y; mean (s.d.) body mass indices (BMIs) of 28.6 (5.4) kg/m(2) and 25.1 (5.4) kg/m2, respectively. MEASUREMENTS: MRI scans of the legs and whole body DXA scans were analysed for muscle and AT content of thigh (20 cm) and lower leg (10 cm) sections; 24 h creatinine excretion was measured. RESULTS: Model A overestimated thigh muscle volume (MRI mean, 2.3 l) substantially (bias 0.36 l), whereas model B underestimated it by only 2% (bias 0.045 l). Lower leg muscle (MRI mean, 0.6 l) was better predicted using model A (bias 0.04 l, 7% overestimate) than model B (bias 0.1 l, 17% underestimate). The 95% limits of agreement were high for these models (thigh,+/- 20%; lower leg,+/- 47%). Model C predictions were more discrepant than those of model B. There was generally less agreement between MRI and all DXA models for AT. Measurement variability was generally less for DXA measurements of FFST (coefficient of variation 0.7 - 1.8%) and fat (0.8 - 3.3%) than model B estimates of muscle (0.5-2.6%) and AT (3.3 - 6.8%), respectively. Despite strong relationships between them, muscle mass was overestimated by creatinine excretion with highly variable predictability. CONCLUSION: This study has shown the value of DXA models for assessment of muscle and AT in leg sections, but suggests the need to re-evaluate some of the assumptions upon which they are based.

The effect of mammographic screening on invasive breast cancer in Western Australia

Objective: To determine whether mammographic screening has affected the presentation of invasive breast cancer in Western Australia. Design: Population-based reviews of the presentation of all invasive breast cancers diagnosed in Western Australia in 1989 and 1994. Setting: Western Australia (population 1.8 million), Active recruitment of women aged 50-69 years for mammographic screening began in 1989. Main outcome measures: Size and stage of invasive breast cancers at diagnosis. Results: From 1989 to 1994, the age-standardised incidence rose from 109 to 123 per 100 000 woman-years, based on 584 and 750 cases, respectively. The proportion of all invasive breast cancers detected as a result of a mammogram increased from 9.2% in 1989 to 34.5% in 1994. Among the cases where relevant information was recorded, the proportion of impalpable tumours increased from 7.7% in 1989 to 27.6% in 1994, and the average size of palpable tumours fell. There was an unexpected increase in the proportion of tumours that were negative on assays for oestrogen and progesterone receptors. Conclusions: A relatively simple and inexpensive clinical review has boosted confidence that the outlay of public monies required to establish and conduct screening in Australia appears likely to yield the reductions in mortality from breast cancer that would be predicted on the basis of the earlier controlled trials of mammography.

Sulfite : Cytochrome c oxidoreductase from Thiobacillus novellus - Purification, characterization, and molecular biology of a heterodimeric member of the sulfite oxidase family

Direct oxidation of sulfite to sulfate occurs in various photo- and chemotrophic sulfur oxidizing microorganisms as the final step in the oxidation of reduced sulfur compounds and is catalyzed by sulfite:cytochrome c oxidoreductase (EC 1.8.2.1), Here we show that the enzyme from Thiobacillus novellus is a periplasmically located alpha beta heterodimer, consisting of a 40.6-kDa subunit containing a molybdenum cofactor and an 8.8-kDa monoheme cytochrome c(552) smbunit (midpoint redox potential, Em(8.0) = +280 mV), The organic component of the molybdenum cofactor was identified as molybdopterin contained in a 1:1 ratio to the Mo content of the enzyme. Electron paramagnetic resonance spectroscopy revealed the presence of a sulfite-inducible Mo(V) signal characteristic of sulfite:acceptor oxidoreductases. However, pH-dependent changes in the electron paramagnetic resonance signal were not detected. Kinetic studies showed that the enzyme exhibits a ping-pong mechanism involving two reactive sites. K-m values for sulfite and cytochrome c(550) were determined to be 27 and 4 mu M, respectively; the enzyme was found to be reversibly inhibited by sulfate and various buffer ions. The sorAB genes, which encode the enzyme, appear to form an operon, which is preceded by a putative extracytoplasmic function-type promoter and contains a hairpin loop termination structure downstream of sorB. While SorA exhibits significant similarities to known sequences of eukaryotic and bacterial sulfite:acceptor oxidoreductases, SorB does not appear to be closely related to any known c-type cytochromes.

The clinical utility of the Hopkins Verbal Learning Test as a screening test for mild dementia

Objective. The purpose of this study was to determine whether the Hopkins Verbal Learning Test (HVLT) could be used as a valid and reliable screening test for mild dementia in older people, and to compare its performance to that of the Mini-Mental State Examination (MMSE). Method. Using a cross-sectional design, we studied three groups of older subjects recruited from a district geriatric psychiatry service: (1) 26 patients with DSM-IV dementia and MMSE scores of 18 or better; (2) 15 patients with psychiatric diagnoses other than dementia; and (3) 15 normal controls. The relationship of each potential cutting point on the HVLT and the MMSE was examined against the independently ascertained DSM-IV diagnoses of dementia using a Receiver Operating Characteristic (ROC) analysis. Results. The subjects consisted of 21 (37.5%) males and 35 (62.5%) females with a mean age of 74.7 (SD 6.1) years and a mean of 8.5 (SD 1.8) years of formal education. ROC analysis indicated that the optimal cutting point for detecting mild dementia in this group of subjects using the HVLT was 18/19 (sensitivity = 0.96, specificity = 0.80) and using the MMSE was 25/26 (sensitivity = 0.88, specificity = 0.93). Conclusions. The HVLT can be recommended as a valid and reliable screening test for mild dementia and as an adjunct in the clinical assessment of older people. The HVLT had better sensitivity than the MMSE in detecting patients with mild dementia, whereas the MMSE had better specificity. Copyright (C) 2000 John Wiley & Sons, Ltd.

Determination of the stability constants of mercury(II) complexes of mixed donor macrobicyclic encapsulating ligands

The reactions of mercury(II) with the mixed donor encapsulating ligands 3,6,16-trithia-6,11,19-triazabicyclo[6.6.6]icosane (AMN(3)S(3)sar) and 1-amino-8-methyl-6,19-dithia-3,10,13,16-tetraazabicyclo[6.6.6]icosane (AMN(4)S(2)sar) have been studied. NMR ligand-ligand competition experiments with the ligands 1,4,8,11-tetraazaeyclotetradecane ([14]aneN(4)), 1-thia-4,7,10-triazacyclododecane ([12]aneN(3)S) and ethylenediaminetetraacetic acid (EDTA) with AMN(3)S(3)sar and Hg(II) indicated that [14]aneN(4) would be an appropriate competing ligand for the, determination of the Hg(II) stability constant. Calculations indicated the ratio of concentrations of AMN3S3sar, [14]aneN(4) and Hg(II) required for the determination of the stability constant ranged from 1:1:1 to 1:5:1. Refinement of the titration curves yielded log(10)K[Hg(AMN(3)S(3)sar)](2+) = 17.7. A similar competition titration resulted in the determination of the stability constant for the AMN(4)S(2)sar system as log(10)K[Hg(AMN(4)S(2)sar)](2+) = 19.5. The observed binding constants for the mixed N/S donor systems and the hexaaza analogues sar (3,6,10,13,16,19-hexaazabicyclo [6.6.6]icosane) and diamsar (1,8-diamino-3,6,10,13,16,19 -hexazabicyclo [6.6.6] icosane (log(10)K-[Hg(diamsar)](2+) = 26.4; log(10)K[Hg(sar)](2+) = 28.1) differ by approximately ten orders of magnitude. The difference is ascribed not to a cryptate effect but to a mismatch in the Hg-N and Hg-S bond lengths in the N/S systems.

Ultrasound evaluation of polymer gel dosimeters

A new method for the evaluation of radiotherapy 3D polymer gel dosimeters has been developed using ultrasound to assess the significant structural changes that occur following irradiation of the dosimeters. The ultrasonic parameters of acoustic speed of propagation, attenuation and transmitted signal intensity were measured as a function of absorbed radiation dose. The dose sensitivities for each parameter were determined as 1.8 x 10(-4) s m(-1) Gy(-1), 3.9 dB m(-1) Gy(-1) and 3.2 V-1 Gy(-1) respectively. All parameters displayed a strong variation with absorbed dose that continued beyond absorbed doses of 15 Gy. The ultrasonic measurements demonstrated a significantly larger dynamic range in dose response curves than that achieved with previously published magnetic resonance imaging (MRI) dose response data. It is concluded that ultrasound shows great potential as a technique for the evaluation of polymer gel dosimeters.

A catalog of HI-selected galaxies from the south celestial cap region of sky

The first deep catalog of the H I Parkes All Sky Survey (HIPASS) is presented, covering the south celestial cap (SCC) region. The SCC area is similar to2400 deg(2) and covers delta < -62&DEG;. The average rms noise for the survey is 13 mJy beam(-1). Five hundred thirty-six galaxies have been cataloged according to their neutral hydrogen content, including 114 galaxies that have no previous cataloged optical counterpart. This is the largest sample of galaxies from a blind H I survey to date. Most galaxies in optically unobscured regions of sky have a visible optical counterpart; however, there is a small population of low-velocity H I clouds without visible optical counterparts whose origins and significance are unclear. The rms accuracy of the HIPASS positions is found to be 1.'9. The H I mass range of galaxies detected is from &SIM;10(6) to &SIM;10(11) M-.. There are a large number of late-type spiral galaxies in the SCC sample (66%), compared with 30% for optically selected galaxies from the same region in the NASA Extragalactic Database. The average ratio of H I mass to B luminosity of the sample increases according to optical type, from 1.8 M-./L-. for early types to 3.2 M-./L-. for late-type galaxies. The H I-detected galaxies tend to follow the large-scale structure traced by galaxies found in optical surveys. From the number of galaxies detected in this region of sky, we predict the full HIPASS catalog will contain &SIM;5000 galaxies, to a peak flux density limit of &SIM;39 mJy (3 σ), although this may be a conservative estimate as two large voids are present in the region. The H I mass function for this catalog is presented in a subsequent paper.

X-linked myoclonic epilepsy with spasticity and intellectual disability - Mutation in the homeobox gene ARX

Objective: To describe a new syndrome of X-linked myoclonic epilepsy with generalized spasticity and intellectual disability (XMESID) and identify the gene defect underlying this disorder. Methods: The authors studied a family in which six boys over two generations had intractable seizures using a validated seizure questionnaire, clinical examination, and EEG studies. Previous records and investigations were obtained. Information on seizure disorders was obtained on 271 members of the extended family. Molecular genetic analysis included linkage studies and mutational analysis using a positional candidate gene approach. Results: All six affected boys had myoclonic seizures and TCS; two had infantile spasms, but only one had hypsarrhythmia. EEG studies show diffuse background slowing with slow generalized spike wave activity. All affected boys had moderate to profound intellectual disability. Hyperreflexia was observed in obligate carrier women. A late-onset progressive spastic ataxia in the matriarch raises the possibility of late clinical manifestations in obligate carriers. The disorder was mapped to Xp11.2-22.2 with a maximum lod score of 1.8. As recently reported, a missense mutation (1058C>T/P353L) was identified within the homeodomain of the novel human Aristaless related homeobox gene (ARX). Conclusions: XMESID is a rare X-linked recessive myoclonic epilepsy with spasticity and intellectual disability in boys. Hyperreflexia is found in carrier women. XMESID is associated with a missense mutation in ARX. This disorder is allelic with X-linked infantile spasms (ISSX; MIM 308350) where polyalanine tract expansions are the commonly observed molecular defect. Mutations of ARX are associated with a wide range of phenotypes; functional studies in the future may lend insights to the neurobiology of myoclonic seizures and infantile spasms.

Cytokine-related genes identified from the RIKEN full-length mouse cDNA data set

To identify novel cytokine-related genes, we searched the set of 60,770 annotated RIKEN mouse cDNA clones (FANTOM2 clones), using keywords such as cytokine itself or cytokine names (such as interferon, interleukin, epidermal growth factor, fibroblast growth factor, and transforming growth factor). This search produced 108 known cytokines and cytokine-related products such as cytokine receptors, cytokine-associated genes, or their products (enhancers, accessory proteins, cytokine-induced genes). We found 15 clusters of FANTOM2 clones that are candidates for novel cytokine-related genes. These encoded products with strong sequence similarity to guanylate-binding protein (GBP-5), interleukin-1 receptor-associated kinase 2 (IRAK-2), interleukin 20 receptor alpha isoform 3, a member of the interferon-inducible proteins of the Ifi 200 cluster, four members of the membrane-associated family 1-8 of interferon-inducible proteins, one p27-like protein, and a hypothetical protein containing a Toll/Interleukin receptor domain. All four clones representing novel candidates of gene products from the family contain a novel highly conserved cross-species domain. Clones similar to growth factor-related products included transforming growth factor beta-inducible early growth response protein 2 (TIEG-2), TGFbeta-induced factor 2, integrin beta-like 1, latent TGF-binding protein 4S, and FGF receptor 4B. We performed a detailed sequence analysis of the candidate novel genes to elucidate their likely functional properties.

Screening for leprosy in immigrants: A decision analysis model

Almost all leprosy cases reported in industrialized countries occur amongst immigrants or refugees from developing countries where leprosy continues to be an important health issue. Screening for leprosy is an important question for governments in countries with immigration and refugee programmes. A decision analysis framework is used to evaluate leprosy screening. The analysis uses a set of criteria and parameters regarding leprosy screening, and available data to estimate the number of cases which would be detected by a leprosy screening programme of immigrants from countries with different leprosy prevalences, compared with a policy of waiting for immigrants who develop symptomatic clinical diseases to present for health care. In a cohort of 100,000 immigrants from high leprosy prevalence regions (3.6/10,000), screening would detect 32 of the 42 cases which would arise in the destination country over the 14 years after migration; from medium prevalence areas (0.7/10,000) 6.3 of the total 8.1 cases would be detected, and from low prevalence regions (0.2/10,600) 1.8 of 2.3 cases. Using Australian data, the migrant mix would produce 74 leprosy cases from 10 years intake; screening would detect 54, and 19 would be diagnosed subsequently after migration. Screening would only produce significant case-yield amongst immigrants from regions or social groups with high leprosy prevalence. Since the number of immigrants to Australia from countries of higher endemnicity is not large routine leprosy screening would have a small impact on case incidence.

Seedling responses of four Australian tree species to toxic concentrations of manganese in solution culture

Little is known about the responses of Australian plants to excess metal, including Mn. It is important to remedy this lack of information so that knowledgeable decisions can be made about managing Mn contaminated sites where inhabited by Australian vegetation. Acacia holosericea, Melaleuca leucadendra, Eucalyptus crebra and Eucalyptus camaldulensis were grown in dilute solution culture for 10 weeks. The seedlings ( 42 days old) were exposed to six Mn treatments viz., 1, 8, 32, 128, 512 and 2048 muM. The order of tolerance to toxic concentrations of Mn was A. holosericea congruent to = E. crebra < M. leucadendra < E. camaldulensis, the critical external concentrations being approximately 5.1, 5.0, 21 and 330 muM, respectively. The critical tissue Mn concentrations for the youngest fully expanded leaf and total shoots were, respectively, 265 and 215 mug g(-1) DM for A. holosericea, 445 and 495 mug g(-1) DM for M. leucadendra, 495 and 710 mug g(-1) DM for E. crebra and 7230 and 6510 mug g(-1) DM for E. camaldulensis. The high tolerance of E. camaldulensis ( as opposed to the sensitivity of E. crebra) to excess Mn raises concern about fauna feeding on the plant and is consistent with hypotheses suggesting the Eucalyptus subgenus Symphomyrtus is particularly tolerant of stress, including excess Mn. The results from this paper provide the first comprehensive combination of growth responses, critical external concentrations, critical tissue concentrations and plant toxicity symptoms for three important Australian genera, viz., Eucalyptus, Acacia and Melaleuca, for use in the management of Mn toxic sites.

Preventing recurrent events long term after coronary artery bypass graft: Suboptimal use of medications in a population study

Background There are few population-based data on long-term management of patients after coronary artery bypass graft (CABG), despite the high risk for future major vascular events among this group. We assessed the prevalence and correlates of pharmacotherapy for prevention of new cardiac events in a large population-based series. Methods A postal survey was conducted of 2500 randomly selected survivors from a state population of patients 6 to 20 years after first CABG. Results Response was 82% (n = 2061). Use of antiplatelet agents (80%) and statins (64%) declined as age increased. Other independent predictors of antiplatelet use included statin use (odds ratio [OR] 1.6, 95% CI 1.26-2.05) and recurrent angina (OR 1.6, CI 1.17-2.06). Current smokers were less likely to use aspirin (OR 0.59, CI 0.4-0.89). Statin use was associated with reported high cholesterol (OR 24.4, CI 8.4-32.4), management by a cardiologist (OR 2.3, CI 1.8-3.0), and the use of calcium channel-blockers. Patients reporting hypertension or heart failure, in addition to high cholesterol, were less likely to use statins. Angiotensin-converting enzyme inhibitors were the most commonly prescribed agents for management of hypertension (59%) and were more frequently used among patients with diabetes and those with symptoms of heart failure. Overall 42% of patients were on angiotensin-converting enzyme inhibitors and 36% on beta-blockers. Conclusions Gaps exist in the use of-recommended medications after CABG. Lower anti-platelet and statin use was associated with older age, freedom from angina, comorbid heart failure or hypertension, and not regularly visiting a cardiologist. Patients who continue to smoke might be less likely to adhere to prescribed medications.

Prevalence of peripheral arterial disease: persistence of excess risk in former smokers

Objective: To determine the age-standardised prevalence of peripheral arterial disease (PAD) and associated risk factors, particularly smoking. Method: Design: Cross-sectional survey of a randomly selected population. Setting: Metropolitan area of Perth, Western Australia. Participants: Men aged between 65-83 years. Results: The adjusted response fraction was 77.2%. Of 4,470 men assessed, 744 were identified as having PAD by the Edinburgh Claudication Questionnaire and/or the ankle-brachial index of systolic blood pressure, yielding an age-standardised prevalence of PAD of 15.6% (95% confidence intervals (CI): 14.5%, 16.6%). The main risk factors identified in univariate analyses were increasing age, smoking current (OR=3.9, 95% CI 2.9-5.1) or former (OR=2.0, 95% CI 1.6-2.4), physical inactivity (OR=1.4, 95% CI 1.2-1.7), a history of angina (OR=2.2, 95% CI 1.8-2.7) and diabetes mellitus (OR=2.1, 95% CI 1.7-2.6). The multivariate analysis showed that the highest relative risk associated with PAD was current smoking of 25 or more cigarettes daily (OR=7.3, 95% CI 4.2-12.8). In this population, 32% of PAD was attributable to current smoking and a further 40% was attributable to past smoking by men who did not smoke currently. Conclusions: This large observational study shows that PAD is relatively common in older, urban Australian men. In contrast with its relationship to coronary disease and stroke, previous smoking appears to have a long legacy of increased risk of PAD. Implications: This research emphasises the importance of smoking as a preventable cause of PAD.

Psychological characteristics of older versus younger persons with a functional gastrointestinal disorder (FGID)

Functional gastrointestinal disorders commonly affect people of all ages, including the elderly. While population-based studies report significant psychological morbidity in people diagnosed with these disorders it is not clear what effect age has in explaining this relationship. We hypothesised that psychological distress would be higher in older versus younger persons with a FGID from the community. A random sample of 4500 subjects were mailed a questionnaire on gastrointestinal symptoms in the past 12 months (response rate = 72%). Of those fulfilling Rome I criteria for a FGID (n = 988) we then classified subjects into older (>60 years) (n =126) versus younger (18-59 years) (n = 862) categories. Psychological variables included anxiety and depression (Delusions Symptom States Inventory) and neuroticism and extroversion (Eysenck Personality Inventory). Quality of life was assessed using the valid SF-12. Anxiety (4.5 vs. 3.1), depression (3.0 vs. 1.8) and neuroticism (5.7 vs. 4.9) were significantly higher in younger versus older subjects with a FGID. While mental functioning (43.1 vs. 48.3) was significantly more impaired in younger versus older subjects, the reverse was found for physical functioning (48.7 vs. 40.8). Younger people with a FGID experience greater