Outdoor, indoor, and personal black carbon exposure from cookstoves burning solid fuels.

Black carbon (BC) emissions from solid fuel combustion are associated with increased morbidity and mortality and are important drivers of climate change. We studied BC measurements, approximated by particulate matter (PM2.5 ) absorbance, in rural Yunnan province, China, whose residents use a variety of solid fuels for cooking and heating including bituminous and anthracite coal, and wood. Measurements were taken over two consecutive 24-h periods from 163 households in 30 villages. PM2.5 absorbance (PMabs ) was measured using an EEL 043 Smoke Stain Reflectometer. PMabs measurements were higher in wood burning households (16.3 × 10(-5) /m) than bituminous and anthracite coal households (12 and 5.1 × 10(-5) /m, respectively). Among bituminous coal users, measurements varied by a factor of two depending on the coal source. Portable stoves (which are lit outdoors and brought indoors for use) were associated with reduced PMabs levels, but no other impact of stove design was observed. Outdoor measurements were positively correlated with and approximately half the level of indoor measurements (r = 0.49, P < 0.01). Measurements of BC (as approximated by PMabs ) in this population are modulated by fuel type and source. This provides valuable insight into potential morbidity, mortality, and climate change contributions of domestic usage of solid fuels.

Indoor concentrations of nitrogen dioxide and sulfur dioxide from burning solid fuels for cooking and heating in Yunnan Province, China.

The Chinese national pollution census has indicated that the domestic burning of solid fuels is an important contributor to nitrogen dioxide (NO2 ) and sulfur dioxide (SO2 ) emissions in China. To characterize indoor NO2 and SO2 air concentrations in relation to solid fuel use and stove ventilation in the rural counties of Xuanwei and Fuyuan, in Yunnan Province, China, which have among the highest lung cancer rates in the nation, a total of 163 participants in 30 selected villages were enrolled. Indoor 24-h NO2 and SO2 samples were collected in each household over two consecutive days. Compared to smoky coal, smokeless coal use was associated with higher NO2 concentrations [geometric mean (GM) = 132 µg/m(3) for smokeless coal and 111 µg/m(3) for smoky coal, P = 0.065] and SO2 [limit of detection = 24 µg/m(3) ; percentage detected (%Detect) = 86% for smokeless coal and 40% for smoky coal, P < 0.001]. Among smoky coal users, significant variation of NO2 and SO2 air concentrations was observed across different stove designs and smoky coal sources in both counties. Model construction indicated that the measurements of both pollutants were influenced by stove design. This exposure assessment study has identified high levels of NO2 and SO2 as a result of burning solid fuels for cooking and heating.

Hepcidin levels in diabetes mellitus and polycystic ovary syndrome.

AIM: Increased body iron is associated with insulin resistance. Hepcidin is the key hormone that negatively regulates iron homeostasis. We hypothesized that individuals with insulin resistance have inadequate hepcidin levels for their iron load. METHODS: Serum concentrations of the active form of hepcidin (hepcidin-25) and hepcidin:ferritin ratio were evaluated in participants with Type 2 diabetes (n = 33, control subjects matched for age, gender and BMI, n = 33) and participants with polycystic ovary syndrome (n = 27, control subjects matched for age and BMI, n = 16). To investigate whether any changes observed were associated with insulin resistance rather than insulin deficiency or hyperglycaemia per se, the same measurements were made in participants with Type 1 diabetes (n = 28, control subjects matched for age, gender and BMI, n = 30). Finally, the relationship between homeostasis model assessment of insulin resistance and serum hepcidin:ferritin ratio was explored in overweight or obese participants without diabetes (n = 16). RESULTS: Participants with Type 2 diabetes had significantly lower hepcidin and hepcidin:ferritin ratio than control subjects (P < 0.05 and P < 0.01, respectively). Participants with polycystic ovary syndrome had a significantly lower hepcidin:ferritin ratio than control subjects (P < 0.05). There was no significant difference in hepcidin or hepcidin:ferritin ratio between participants with Type 1 diabetes and control subjects (P = 0.88 and P = 0.94). Serum hepcidin:ferritin ratio inversely correlated with homeostasis model assessment of insulin resistance (r = -0.59, P < 0.05). CONCLUSION: Insulin resistance, but not insulin deficiency or hyperglycaemia per se, is associated with inadequate hepcidin levels. Reduced hepcidin concentrations may cause increased body iron stores in insulin-resistant states.

Indoor air pollution and lung function growth among children in four Chinese cities.

UNLABELLED: Ambient air pollution has been associated with decreased growth in lung function among children; but little is known about the impact of indoor air pollution. We examined relationships between indoor air pollution metrics and lung function growth, among children (n = 3273) aged 6-13 years living in four Chinese cities. Lung function parameters (FVC and FEV(1) ) were measured twice a year. Questionnaires were used to determine home coal burning and ventilation practices. Generalized estimating equations were used to examine associations. Use of coal as a household fuel was associated with 16.5 ml/year lower (33%, P < 0.001) and 20.5 ml/year lower (39%, P < 0.001) growth in children's FEV(1) and FVC, respectively. FEV(1) growth was 10.2 ml/year higher (20%, P = 0.009), and FVC growth was 17.0 ml/year higher (33%, P < 0.001) among children who lived in houses with the presence of a ventilation device. Among children living in houses where coal was used as a fuel and no ventilation devices were present, adjusted FVC and FEV(1) growth, respectively, were 37% and 61% that of the average growth per year in the full cohort. This suggests that household coal use may cause deficits in lung function growth, while using ventilation devices may be protective of lung development. PRACTICAL IMPLICATIONS: Nearly 3.4 billion people use solid fuels in homes for cooking and/or heating. We report the following findings from a longitudinal study: (i) household coal use is significantly associated with reduction in children's lung function growth and (ii) the use of household ventilation devices is significantly associated with higher lung function growth, particularly among children living in households where coal is used as a fuel. These findings not only provide evidence that indoor coal use impairs children's lung development but also point to the importance of improving ventilation conditions in reducing harmful effects of indoor air pollution sources.

Differential effects of smoking on lung cancer mortality before and after household stove improvement in Xuanwei, China.

BACKGROUND: In Xuanwei County, Yunnan Province, China, lung cancer mortality rates in both males and females are among the highest in China. METHODS: We evaluated differential effects of smoking on lung cancer mortality before and after household stove improvement with chimney to reduce exposure to smoky coal emissions in the unique cohort in Xuanwei, China. Effects of independent variables on lung cancer mortality were measured as hazard ratios and 95% confidence intervals using a multivariable Cox regression model that included separate time-dependent variables for smoking duration (years) before and after stove improvement. RESULTS AND CONCLUSION: We found that the effect of smoking on lung cancer risk becomes considerably stronger after chimney installation and consequent reduction of indoor coal smoke exposure.

Lung cancer and indoor air pollution in Xuan Wei, China.

In Xuan Wei County, Yunnan Province, lung cancer mortality is among China's highest and, especially in females, is more closely associated with indoor burning of "smoky" coal, as opposed to wood or "smokeless" coal, than with tobacco smoking. Indoor air samples were collected during the burning of all three fuels. In contrast to wood and smokeless coal emissions, smoky coal emission has high concentrations of submicron particles containing mutagenic organics, especially in aromatic and polar fractions. These studies suggested an etiologic link between domestic smoky coal burning and lung cancer in Xuan Wei.

Development of a novel immunoassay for the iron regulatory peptide hepcidin.

To date there have been few published immunoassays for the important iron regulator hepcidin. This study describes a novel competitive radioimmunoassay (RIA) for the bioactive hepcidin peptide. A rabbit anti-hepcidin polyclonal antibody was produced using synthetic hepcidin radiolabelled with 125I to produce a competitive RIA. Normal patient (n=47) samples were collected and assayed for hepcidin to determine a reference range. Other patient groups collected were ulcerative colitis (UC; n=40), iron deficiency anaemia (IDA; n=15), chronic kidney disease not requiring dialysis (CKD; n=45) and chronic kidney disease requiring dialysis (HCKD; n=94). Detection limit of the assay was determined as 0.6 ng/mL. Intra-assay precision was 5 ng/mL (7.2%) and 50 ng/mL (5.8%), interassay precision was 5 ng/mL (7.6%) and 50 ng/mL (6.7%). Analytical recovery was 98% (5 ng/mL), 94% (10 ng/mL) and 97% (50 ng/mL). The assay was linear up to 200 ng/mL. No demonstrable cross-reactivity with human insulin, glucagon I, angiotensinogen I, beta-defensin 1-4, alpha-defensin-1 and plectasin was observed. There was significant correlation (r=0.96, P < or = 0.0001) between the hepcidin RIA and an established hepcidin SELDI-TOF-MS method. Analysis of the normal human samples gave a reference range of 1.1-55 ng/mL for hepcidin. Further statistical evaluation revealed a significant difference between male and female hepcidin levels. There was significant correlation between hepcidin and ferritin in the control group (r=0.6, P < or = 0.0001). There was also a significant difference between the normal and disease groups (P < or = 0.0001). Healthy volunteers (n=10) showed a diurnal increase in plasma hepcidin at 4.00 pm compared to 8.00 am. A robust and optimised immunoassay for bioactive hepcidin has been produced and the patient sample results obtained further validates the important role of hepcidin in iron regulation, and will allow further investigation of this important peptide and its role in iron homeostasis.

High success rate of TB treatment among Bhutanese refugees in Nepal.

SETTING: Camps for refugees from Bhutan in south-east Nepal. OBJECTIVES: To evaluate the outcome of treatment of tuberculosis (TB) cases in the refugee camps. DESIGN: Cohort analysis of results of treatment of cases started on treatment from mid-July 1999 to mid-July 2004. RESULT: A total of 1214 patients with TB were notified in the programme. Among these, 631 (52%) were new smear-positive pulmonary tuberculosis (PTB) cases, 175 (14%) new smear-negative PTB cases, 290 (24%) new extra-pulmonary TB (EPTB) cases and 118 (10%) smear-positive retreatment cases. Treatment success was achieved in 1061 (94%). The proportion of new non-smear-positive cases who died on treatment was significantly higher than the corresponding figure for new smear-positive cases (RR 7.57, 95%CI 3.74-15.32 for new smear-negative and 4.22, 95%CI 2.08-8.55 for EPTB). CONCLUSION: High cure rates and low bacteriological failure rates can be achieved in refugee settings if there is close coordination and collaboration between the local health agencies and the National Tuberculosis Programme of the host country.

Surveillance of sexually transmitted diseases in general practice: a description of trends in the Royal College of General Practitioners Weekly Returns Service between 1994 and 2001.

This paper describes the incidence of sexually transmitted infections (STIs) recorded in the Weekly Returns Service (WRS) between 1994 and 2001. There were approximately 76,500 new diagnoses of STIs (7500 males, 71,000 females) and associated syndromes. Candidiasis was the commonest condition reported in males and females followed by pelvic inflammatory disease. The ratio of males to females was 7.1 for non-specific urethritis, and 9.1 and 2.1 for Reiter's syndrome and pediculosis pubis, respectively. The incidence of anogenital warts and genital herpes changed little over time. New diagnoses of genital herpes were higher in females than in males (ratio 2.8:1), whereas the mean annual incidence of genital warts was similar in males and females. The WRS provides an insight into the burden of STI diagnoses, and diagnoses related to STIs that are managed in general practice, and as such has the potential to make a substantial contribution to STI surveillance in England.

The suppression of drug-induced apoptosis by activation of v-ABL protein tyrosine kinase.

Cells with a temperature-sensitive mutant of the v-abl oncoprotein (IC.DP) were treated with the anticancer drugs melphalan or hydroxyurea. At the restrictive temperature for v-ABL protein tyrosine kinase activity, drug-treated IC.DP cells died by apoptosis. In contrast, apoptotic cell death induced by either drug was suppressed when v-ABL was active. However, melphalan-induced accumulation of cells in the S and G2-M phases of the cell cycle was unaffected by v-ABL activation. Moreover, the continuous presence of v-ABL activity was necessary to suppress apoptosis. This suggested that melphalan had interacted with DNA and that v-ABL activity prevented the coupling of drug-induced damage to the apoptotic pathway. IC.DP cells exhibited similar levels and subcellular localization of the BCL-2 protein irrespective of v-ABL activation status, thus v-ABL-mediated cell survival appeared to be independent of BCL-2.

A novel role for IRF-1 as a suppressor of apoptosis.

The tumour suppressor IRF-1 is a transcription factor involved in the induction of apoptosis in several in vitro systems. Post-lactational involution of the mammary gland is characterized by extensive apoptosis of the epithelial cells. We have previously shown that signal transducer and activator of transcription (Stat) 3 drives apoptosis and involution in the mouse mammary gland. Since one of the downstream targets of the Stat signalling pathway is IRF-1, we have used IRF-1 knockout mice to address the potential role of this transcription factor in involution. Surprisingly, in the absence of IRF-1 significantly higher numbers of apoptotic cells were found in involuting glands at 48 h compared to control glands. In addition, the alveolar structure in IRF-1 null mammary glands had collapsed whereas in control glands the alveoli remained intact and distended. However, by 72 h control and null glands were morphologically similar suggesting that IRF-1 suppresses apoptosis only during the early, reversible, stage of involution. This suggests a survival role for IRF-1 in mammary epithelia and demonstrates a novel role for IRF-1 in vivo--suppression of premature epithelial apoptosis during mammary gland involution.

p53-dependent apoptosis induced by proteasome inhibition in mammary epithelial cells.

We have examined the effects of inhibition of the 26S proteasome in a murine mammary cell line, KIM-2 cells using the peptide aldehyde inhibitor MG132. These studies have demonstrated a clear requirement for proteasome function in cell viability. Induction of apoptosis was observed following MG132 treatment in KIM-2 cells and this death was shown to be dependent on the cell actively traversing the cell cycle. KIM-2 cells were generated using a temperature sensitive T-antigen (Tag) and studies at the permissive temperature (33 degrees C) have shown that a Tag binding protein was essential for this apoptotic response. Studies in two additional cell lines, HC11, which is a mammary epithelial cell line carrying mutant p53 alleles and p53 null ES cells suggest that p53 is actively required for the apoptosis induced as a consequence of proteasome inhibition. These results suggest a pivotal role for the 26S proteasome degradation pathway in progression through the cell cycle in proliferating cells.

Application of solid-phase antibodies to radioimmunoassay. Evaluation of two polymeric microparticles, Dynospheres and nylon, activated by carbonyldiimidazole or tresyl chloride.

Two types of polymeric microparticle, Dynospheres and reprecipitated acid-hydrolysed nylon 6/6, and two methods of activating these particles with either tresyl chloride or carbonyldiimidazole (CDI) prior to covalent linkage of antibodies were investigated with a view towards their respective adoption for the preparation of general solid-phase reagents for immunoassay applications. Activation of each particle and coupling of antibodies was rapid irrespective of the activator. CDI proved to be the activator of choice since it was cheap, less hazardous, more efficient and less pH dependent than tresyl chloride. Both types of microparticle remain buoyant during the RIA incubation periods and form stable pellets after centrifugation. In second antibody applications immobilisation of the first antibody occurs with a short incubation period of 30 min. Nylon microparticles have a higher antibody-coupling capacity and are the particles of choice in both first and second antibody applications. However, the nylon microparticles possess marginally higher non-specific binding characteristics.

Performance of the two-site immunoradiometric assay for serum thyroid-stimulating hormone. Effects of changes in solid-phase matrix and antibody coupling chemistry.

Ten solid-phases were evaluated for their usefulness in a two-site immunoradiometric assay for serum thyroid-stimulating hormone. The criteria used to assess each reagent included the minimum detection limit attainable, the change of binding over the concentration range (signal: noise ratio), and ease of preparation of the reagents. Of all the solid phases tested, Sepharose CL-4B and activated CH-Sepharose 4B showed the characteristics best suited to IRMA, while epoxy-activated Sepharose 6B and Ultrogel ACA-44 were marginally less effective.

Production and characterisation of monoclonal antibodies to parathyroid hormone (1-34).

Monoclonal antibodies to the biologically active N terminal region of parathyroid hormone (PTH) suitable for use in the measurement of circulating PTH concentrations have proved difficult to produce. In this study, no serum PTH antibody titres could be detected in mice using synthetic human PTH (1-34) (free or coupled to albumin) or PTH (1-10) (coupled to keyhole limpet haemocyanin) as immunogen. A consistent response to PTH (1-34) peptide was obtained in DA rats. We have produced five monoclonal antibodies to PTH (1-34) derived from the fusion of DA rat spleen cells and the mouse myeloma line X63 Ag.8.653. Bulk production of the antibodies was achieved using congenitally athymic mice for ascites production. Antibody assessment studies revealed the antibodies to be sensitive to the oxidation state of the methionine residues in PTH (1-34). Two of the antibodies, 3B3 and 6E3, were shown to be of potential use in measuring circulating PTH (1-84) when used in combination with available antibodies to C terminal PTH. A third antibody, 4G3, which failed to recognise PTH (1-84) when used in combination with 3B3, formed the basis of a specific assay for PTH (1-34).

An epidemiological study of lung cancer in Xuan Wei County, China: current progress. Case-control study on lung cancer and cooking fuel.

In Xuan Wei County, Yunnan Province, lung cancer mortality rates are among China's highest in males and females. Previous studies have shown a strong association of lung cancer mortality with air pollution from "smoky" coal combustion. In the present quantitative risk assessment of indoor air pollution study, the result strongly shows an obvious on-site exposure-response relationship between benzo[a]pyrene concentration in indoor air and lung cancer mortality and strongly supports the hypothesis that indoor air pollution is the main risk factor in inducing lung cancer in Xuan Wei County. In the present case-control study, the result shows that in females, the presence of lung cancer is statistically significantly associated with chronic bronchitis and family history of lung cancer. The results also suggest an association of lung cancer with duration of cooking food, but not with passive smoking. In males, the presence of lung cancer is associated with smoking, bronchitis, family history of lung cancer, and personal history of cooking food.

Application and evaluation of portable field instruments for measuring forced expiratory volume of children and adults in environmental health surveys.

In support of Health Effects Research Studies, pulmonary function tests are periodically administered to a large number of children. The ventilatory performance of these children is being evaluated by measuring the 0.75-sec forced expiratory volume (FEV(0.75)) with a waterless mechanical volume spirometer used in conjunction with an electronic timing unit. During a 1-yr testing period, operation with the volume spirometer and the EPA designed electronic timing unit proved to be highly successful. The volume spirometer was found to be more advantageous in conducting tests at remote field stations than the water spirometer and other electronic instruments which measure flow rate with a transducer element. The volume spirometer is lightweight, easy to operate, and has the capability of easy and accurate field calibration when used in conjunction with the electronic timing unit. Presently the volume spirometer and EPA designed electronic timing package are employed in all Community Health and Surveillance System (CHESS) pulmonary function testing studies.

Smoking and other risk factors for lung cancer in Xuanwei, China.

In Xuanwei County, Yunnan Province, lung cancer mortality rates are among the highest in China in both males and females. Previous studies have shown a strong association of lung cancer mortality with indoor air pollution from 'smoky' coal combustion. In the present case-control study, 110 newly-diagnosed lung cancer patients and 426 controls were matched with respect to age, sex, occupation (all subjects were farmers), and village of residence (which provided matching with respect to fuel use). This design allowed assessment of known and suspected lung cancer risk factors other than those mentioned above. Data from males and females were analysed by conditional logistic regression. In females who do not smoke, the presence of lung cancer was statistically significantly associated with chronic bronchitis (odds ratio [OR] = 7.37, 95% confidence interval [Cl]: 2.40-22.66) and family history of lung cancer (OR 4.18, 95% Cl: 1.61-10.85). Females' results also suggested an association of lung cancer with duration of cooking food (OR 1.00, 9.18 and 14.70), but not with passive smoking (OR 0.77, 95% Cl: 0.30-1.96). In males, lung cancer was significantly associated with chronic bronchitis (OR 7.32, 95% Cl: 2.66-20.18), family history of lung cancer (OR 3.79, 95% Cl: 1.70-8.42), and personal history of cooking food (OR 3.36, 95% Cl: 1.27-8.88). In males a dose-response relationship of lung cancer with smoking index (years of smoking*amount of smoking) was shown by risks of 1.00, 2.61, 2.17 and 4.70.

Papuloerythroderma. Another case of a new disease.

We describe a case of papuloerythroderma. This is a distinctive clinical entity characterized by pruritus, red-brown flat-topped papules exhibiting the "deck-chair" sign, eosinophilia, and lymphopenia. We propose that the Langerhans cell may have a central role in the pathogenesis of papuloerthroderma and we describe an excellent response to photochemotherapy.

Development and evaluation of a simple, direct, solid-phase radioimmunoassay of serum cortisol from readily available reagents.

A simple, rapid solid-phase radioimmunoassay for serum cortisol was developed using cortisol antibody distributed by the Scottish Antibody Production Unit and commercially available radioiodinated cortisol ligand. The assay involves a 1-h incubation at ambient temperature, using the antibody covalently linked by the easily performed carbonyldiimidazole method, to microcrystalline cellulose. A detailed comparison of the accepted 0.125 mol/l citrate, pH 4.0, and an alternative 0.1 mol/l phosphate/8-anilinonaphthalene sulphonic acid, pH 7.4, diluent demonstrated similar precision (within-assay 10% to 5%; between-assay 11% to 6% over the range 100-1000 nmol/l cortisol) and recovery (median recoveries: phosphate 98.6%, citrate 99.5%). Linear regression analysis of human serum cortisol concentrations in comparison with the 'Amerlex' cortisol RIA kit gave the following results: citrate = 1.029. 'Amerlex' - 3.5 nmol/l (n = 80, r = 0.967); phosphate = 1.017, 'Amerlex' + 26.2 nmol/l (n = 80, r = 0.961). Phosphate, pH 7.4 diluent was adopted as the diluent of choice, since it was economical of antibody and maintained good precision over a wider working range of cortisol concentration.