Fatal pulmonary infection related to Nocardiopsis dassonvillei in a patient with chronic obstructive pulmonary disease.

Nocardiopsis species are aerobic, gram-positive, non-acid fast rods isolated from soil, waters, and animals. They are opportunistic human pathogens, but very few cases have been published so far. We report the first case of fatal pulmonary infection related to Nocardiopsis dassonvillei in an immunocompetent patient with chronic obstructive pulmonary disease.

[Spider bite or infection caused by Panton Valentine leucocidin-producing Staphylococcusaureus?] / Morsure d'araignée ou infection à Staphylococcusaureus producteur de toxine de Panton Valentine ?

INTRODUCTION: Spiders, especially those of the genus Loxoceles such as L. rufescens, endemic in Mediterranean regions, are frequently reported as causes of venom poisoning in humans in the south of France. The most common signs consist of cutaneous necrosis presenting initially as inflammatory cellulitis and progressing towards the emergence of a necrotic centre. PATIENTS AND METHODS: We report 4 cases, initially considered as spider bites due to their sudden occurrence and pain. Rigorous clinical examination coupled with collection of samples for laboratory analysis ultimately enabled the diagnosis to be corrected to one of suppurative skin infection caused by Staphylococcusaureus producing the cytotoxin Panton Valentine leucocidin. DISCUSSION: These observations highlight the potential for confusion between spider bites and infections with PVL-producing S. aureus.

An evaluation of the completeness of reporting of childhood tuberculosis.

The sensitivity of the Enhanced Tuberculosis Surveillance (ETS) scheme for monitoring tuberculosis in children is unknown. We used the British Paediatric Surveillance Unit (BPSU) reporting scheme to conduct a prospective observational study of tuberculosis in children aged <16 yrs in the UK. Reported cases were then matched with records from the ETS database. A total of 320 cases were reported to the BPSU between January and December 2004. We estimated that there were 557 paediatric cases in England, Wales and Northern Ireland in 2004: 222 (40%) cases reported to both BPSU and ETS, 98 (18%) reported to BPSU but not ETS and 237 (42%) reported to ETS but not BPSU. Children aged <5 yrs were significantly less likely to be reported to ETS compared with older children (p<0.01). There is substantial under-reporting of childhood tuberculosis, especially of children aged <5 yrs. ETS provides a representative picture of the demographics but may miss approximately 20% of cases. This should be taken into account when planning training and resource requirements for tuberculosis. Increased efforts are needed to ensure that all paediatric cases are reported to ETS.

Tuberculosis in the United Kingdom and Republic of Ireland.

AIMS: To describe the clinical features, diagnosis and management of children with tuberculosis in the United Kingdom and Republic of Ireland. METHODS: Cases of culture-confirmed and clinically diagnosed tuberculosis were reported to the British Paediatric Surveillance Unit from December 2003 to January 2005. RESULTS: 385 eligible cases were reported. Pulmonary disease was present in 154 (40%) children. Just over half (197, 51%) of children presented clinically and most of the remainder (166, 43%) at contact tracing. A probable source case was identified for 73/197 (36%) of the children presenting clinically. The majority (253, 66%) of children had a microbiological and/or histological investigation, and culture results were available for 240 (62%), of whom 102 (26%) were culture positive. Drug resistance was reported in 15 (0.4%) cases. 44% (128/292) of non-white children did not receive the recommended quadruple drug therapy. Seven children died. Only 57% (217) of children were managed by a paediatric subspecialist in respiratory or infectious diseases or a general paediatrician with a special interest in one of these areas. Fewer than five cases were reported from 119/143 (83%) respondents and 72 of 96 (75%) centres. CONCLUSIONS: Many paediatricians and centres see few children with tuberculosis. This may affect adherence to national guidelines. Managed clinical networks for children with tuberculosis may improve management and should be the standard of care.

The selective MMP-12 inhibitor, AS111793 reduces airway inflammation in mice exposed to cigarette smoke.

BACKGROUND: Macrophage elastase (MMP-12) is involved in the inflammatory process of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate in mice the effect of MMP-12 inhibition on the inflammatory process induced by cigarette smoke (CS) or by lipopolysaccharide (LPS) exposure of the airways. EXPERIMENTAL APPROACH: C57BL/6 mice were given, orally, either the selective MMP-12 inhibitor AS111793 (3, 10, 30 and 100 mg kg(-1)), the PDE-4 inhibitor roflumilast (3 mg kg(-1)) or vehicle, then exposed to CS (for 3 days) or to LPS (100 microg mL(-1), 30 min). Subsequent to the last smoke or LPS exposure, bronchoalveolar lavages (BAL) were performed and lungs were removed and homogenized to analyze various markers of inflammation at appropriate times. KEY RESULTS: Inhibition of MMP-12 by AS111793 (10 and 30 mg kg(-1)) was associated with a reduction of the increase in neutrophil number in BAL fluids after 4 days and of macrophages after 11 days. On day 4, AS111793 also significantly reduced all the inflammation markers that had increased after CS exposure, including soluble TNF receptors I and II, MIP-1gamma, IL-6 and pro-MMP-9 activity in BAL fluids, and KC/CXCL1, fractalkine/CX3CL1, TIMP-1 and I-TAC/CXCL11 in lung parenchyma. In contrast, inhibition of MMP-12 did not reduce neutrophil influx, pro-MMP-9 activity or KC/CXCL1 release in BAL fluids of mice exposed to LPS. CONCLUSION: Inhibition of MMP-12 with AS111793, reduced the inflammatory process associated with exposure of mice to CS, strongly suggesting a specific involvement of MMP-12 in lung inflammation following CS exposure.

AS601245, a c-Jun NH2-terminal kinase (JNK) inhibitor, reduces axon/dendrite damage and cognitive deficits after global cerebral ischaemia in gerbils.

BACKGROUND AND PURPOSE: Based on their proven ability, in animal models of stroke, to reduce damage to brain grey matter, many drugs have been tested in clinical trials but without success. Failure to save axons from injury and to protect functional outcome has been proposed as the major reason for this lack of success. We have previously demonstrated in two rodent models of cerebral ischaemia, that AS601245 (1,3-benzothiazol-2-yl (2-([2-(3-pyridinyl) ethyl] amino)-4 pyrimidinyl) acetonitrile), an inhibitor of the c-Jun NH(2)-terminal kinase (JNK), has neuroprotective properties. The aim of the present study was to further investigate if AS601245 in addition to its ability to protect neurons also could protect neurites and preserve memory after cerebral ischaemia, in gerbils. EXPERIMENTAL APPROACH: Using immunohistochemical techniques and a behavioural test, we studied the effect of the compound AS601245 on neurodegeneration and cognitive deficits after global cerebral ischaemia in gerbils. KEY RESULTS: At a dose of 80 mg kg(-1), i.p., AS601245 reduced damage to neurites by 67% (P<0.001 versus controls) and activation of astrocytes by 84% (P<0.001 versus controls). In addition, AS601245 (80 mg kg(-1), i.p.) prevented ischaemia-induced impairment of memory in the inhibitory avoidance task model. CONCLUSIONS AND IMPLICATIONS: The present results suggest that AS601245 reduced damage to neurites and decreased astrogliosis following global ischaemia and also improved long-term memory, supporting JNK inhibition as a promising therapeutic strategy for ischaemic insults to the CNS.

Asbestos bodies in the sputum of asbestos workers: correlation with occupational exposure.

A cross-sectional medical survey including collection of three consecutive sputum samples was carried out among 270 retired workers of a textile and friction materials factory, in order to investigate the relationship between asbestos body identification and asbestos exposure. The individual cumulative asbestos exposure, determined by means of a plant-specific job-exposure matrix based on asbestos air measurements in the workshops, proved to be heavy with a mean cumulative exposure of 217 fibres x mL(-1) x yr. Macrophages and asbestos bodies were identified in sputum samples by light microscopy. The lung origin of the sputum, suggested by the presence of macrophages and/or asbestos bodies, was confirmed in 82.6% of subjects, and 53% of these samples were positive for asbestos bodies. The prevalence of asbestos bodies was not related to sex, smoking status or latency. Conversely, multivariate analysis showed a positive relationship with cumulative exposure, duration and intensity of exposure to asbestos, as well as age and time since retirement. These findings suggest that sputum analysis for asbestos bodies may remain a relevant and noninvasive marker of heavy occupational exposure to asbestos, even years after retirement. Owing to the new perspectives in lung cancer screening, it might contribute to the identification of high-risk subjects.

Detection of enterovirus viraemia in blood donors.

BACKGROUND AND OBJECTIVES: The infrastructure established for screening blood donations for hepatitis C virus has enabled large-scale population testing for other viruses which are potentially transmissible by transfusion of blood components and plasma-derived blood products. We have measured the frequency of viraemia of enteroviruses and parechoviruses in 83 600 Scottish blood donors to allow an initial assessment of their risk to blood safety. MATERIALS AND METHODS: Plasma samples collected from blood donors over 7 calendar months were tested anonymously in mini-pools of 95 donations, by polymerase chain reaction (PCR) for human enterovirus and parechovirus sequences. RESULTS: A total of 19 mini-pools, from the 880 that were tested, were PCR-positive for enterovirus RNA, predicting a donor prevalence of 0.023%. Enterovirus sequences were not detected in factor VIII or IX clotting factor concentrates. None of the 230 mini-pools or concentrates contained detectable parechovirus RNA. CONCLUSIONS: The prevalence of enterovirus viraemia detected in this study predicts that at least 1000 enterovirus-contaminated blood components are transfused per year in the UK. The frequency of transmission and clinical outcome after exposure to enterovirus-contaminated blood components in recipients is unknown.

Influence of carbonic anhydrase activity in terrestrial vegetation on the 18O content of atmospheric CO2.

The oxygen-18 (18O) content of atmospheric carbon dioxide (CO2) is an important indicator of CO2 uptake on land. It has generally been assumed that during photosynthesis, oxygen in CO2 reaches isotopic equilibrium with oxygen in 18O-enriched water in leaves. We show, however, large differences in the activity of carbonic anhydrase (which catalyzes CO2 hydration and 18O exchange in leaves) among major plant groups that cause variations in the extent of 18O equilibrium (theta(eq)). A clear distinction in theta(eq) between C3 trees and shrubs, and C4 grasses makes atmospheric C18OO a potentially sensitive indicator to changes in C3 and C4 productivity. We estimate a global mean theta(eq) value of approximately 0.8, which reasonably reconciles inconsistencies between 18O budgets of atmospheric O2 (Dole effect) and CO2.

Multidrug-resistant tuberculosis: this is the cost.

The costs of multidrug-resistant tuberculosis (MDR TB) reach far beyond the cost of the clinical treatment of the patient. The first impact of the discovery of MDR TB in a population is the need to recognize that all TB patients have the potential of being MDR. Public health measures to prevent the spread of MDR TB, or to control or reverse the problem where spread has already occurred, can be extremely expensive to implement. At the level of the individual patient, the second-line drugs used to treat MDR TB are more expensive, and the remaining first-line drugs will have to be used for a longer time than in drug-susceptible TB. Negative-pressure units add to the costs of treatment, as does the increased nursing intensity required. The cost to the wider economy includes lost productivity and lost tax revenue to the state as well as the cost of supporting the family if the patient is the breadwinner.

Resource implications of patients with multidrug resistant tuberculosis.

BACKGROUND: Multidrug resistant tuberculosis (MDR TB) requires a complex drug regimen and lengthy multidisciplinary care. The financial cost of successful management of each case is potentially large. METHODS: The costs of managing nine HIV negative patients with pulmonary MDR TB were compared with 18 age group and ethnicity matched controls with fully sensitive disease. Calculations included: cost of outpatient visits and inpatient stays including negative pressure isolation; costs of drug provision and toxicity monitoring; costs of additional procedures and multidisciplinary referrals. RESULTS: The mean cost of managing a case of pulmonary MDR TB was in excess of 60,000 pounds sterling and for sensitive disease it was 6040 pounds sterling. CONCLUSIONS: Clinicians and healthcare commissioning authorities may both be underestimating the costs of managing MDR TB, and accordingly the consequences for units dealing with such cases may be serious. Funding of care for MDR TB in the UK requires strategic decisions at regional or governmental level.

Natural history of haemoglobin levels in female blood donors with haemoglobin levels of 120-124 g/l at presentation.

BACKGROUND AND OBJECTIVES: In order to assess the effects of proposed changes to UK guidelines, female blood donors with venous haemoglobin (Hb) levels of 120-124 g/l were followed up over a period of 18 months in order to assess frequency of attendance and ability to donate in relation to changes in Hb and red cell indices, and to determine the effects of inter-donation interval and iron supplementation on outcomes. MATERIALS AND METHODS: Venous samples were analysed using the Haemocue haemoglobinometer at each attendance, and a donation was taken if the Hb was 120 g/l or greater. Full blood counts were done on each sample using the Coulter Model T890. A postal questionnaire was used to elicit additional information, including use of iron supplements. RESULTS: The 392 donors enrolled in the study gave 655 subsequent attendances, resulting in 468 donations (1.5 donations/donor/year). Donors who subsequently had Hb <120 g/l had a tendency to lower initial mean corpuscular volume (MCV), but MCV could not be used as an indicator of future performance. 23% of donors reported use of iron supplements, but those donating 3 times or more were no more likely to use iron supplementation (20%). No statistical relationship was found between inter-donation interval and ability to donate at subsequent attendances. CONCLUSIONS: Female donors with borderline Hb levels proved to be highly committed, with a donation rate of 1. 5/donor/year during the period of follow-up. MCV is not a useful predictor of ability to donate in the future. This subset of the donor population shows wide variation in Hb level over time, and this is largely independent of iron supplementation or inter-donation interval.

Internal conductance to CO(2) diffusion and C(18)OO discrimination in C(3) leaves.

(18)O discrimination in CO(2) stems from the oxygen exchange between (18)O-enriched water and CO(2) in the chloroplast, a process catalyzed by carbonic anhydrase (CA). A proportion of this (18)O-labeled CO(2) escapes back to the atmosphere, resulting in an effective discrimination against C(18)OO during photosynthesis (Delta(18)O). By constraining the delta(18)O of chloroplast water (delta(e)) by analysis of transpired water and the extent of CO(2)-H(2)O isotopic equilibrium (theta(eq)) by measurements of CA activity (theta(eq) = 0.75-1.0 for tobacco, soybean, and oak), we could apply measured Delta(18)O in a leaf cuvette attached to a mass spectrometer to derive the CO(2) concentration at the physical limit of CA activity, i.e. the chloroplast surface (c(cs)). From the CO(2) drawdown sequence between stomatal cavities from gas exchange (c(i)), from Delta(18)O (c(cs)), and at Rubisco sites from Delta(13)C (c(c)), the internal CO(2) conductance (g(i)) was partitioned into cell wall (g(w)) and chloroplast (g(ch)) components. The results indicated that g(ch) is variable (0.42-1.13 mol m(-2) s(-1)) and proportional to CA activity. We suggest that the influence of CA activity on the CO(2) assimilation rate should be important mainly in plants with low internal conductances.