[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.

Abrogation by subsequent feeding of antibody response including IgE, in parenterally immunized mice.

We have investigated the possibility of oral administration of ovalbumin (OVA) to prevent a secondary antibody response and interrupt reaginic antibody production. Repeated feeding seems necessary for both. Quality of results was dependent on the number of ingestions. Differences in abrogation of antibody response between mice strains were observed. Best results were obtained with AKR mice, good suppression was seen in C3H strain, and inconsistent results were obtained with DBA/2. 10 OVA oral doses were necessary to prevent a secondary antibody response in parenterally immunized mice, but 4 doses interrupted reaginic production in sensitized AKR mice. These results demonstrate that antigen feeding can prevent a secondary antibody response and interrupt reaginic antibody production.

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.

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.

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.

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.

Segmental variation in the arborization of identified neurons in the leech central nervous system.

Mechanosensory and motor neurons in the central nervous system of the leech have been examined by intracellular injection of horseradish peroxidase and electrophysiological mapping of their peripheral fields to determine how the arborizations of homologous cells are influenced by their segmental position. The branching patterns of annulus erector (AE) motoneurons in ganglia near the head and tail were found to be more extensive than those of cells in midbody ganglia. As in midbody ganglia, the peripheral fields of AE motoneurons in adjacent ganglia near the head and tail overlapped extensively, but the subfields innervated by individual branches of a single AE motoneuron showed little or no overlap. No AE motoneurons were found in the head ganglion or in the 20th and 21st free segmental ganglia. The branching pattern of touch-sensitive mechanosensory cells showed a similar segmental variation; touch cells in ganglia near the head and tail had more extensive arborizations than those in midbody ganglia. The rostrocaudal position along the cord at which the branching pattern changed from that characteristic of midbody ganglia to one with a more extensive arborization differed for different types of neurons. These findings demonstrate that a cell's pattern of arborization is not determined by a simple segmental difference between ganglia and suggest that during development neurons respond individually to cues that vary along the length of the cord.

Pharmacological and functional evidence for extracellular 3,4-dihydroxyphenylacetic acid as an index of metabolic activity of the adrenergic neurons: an in vivo voltammetry study in the rat rostral ventrolateral medulla.

Catecholamine metabolism was studied in vivo in the C1 adrenergic area of the rostral ventrolateral medulla oblongata in rats, using differential normal pulse voltammetry coupled with an activated carbon fiber microelectrode. Pharmacological evidence indicates that 3,4-dihydroxyphenylacetic acid, the major dopamine metabolite, is responsible for the electrochemical signal appearance in the C1 group, and that it reflects the catecholamine synthesis rate, as previously reported in the locus coeruleus. Indeed, 3,4-dihydroxyphenylacetic acid was estimated to be formed from 77% of the intracellular dopamine, since its synthesis was increased by only 23%, after blockade of the dopamine-beta-hydroxylase activity. Neuronal activation by retrograde electrical stimulation increased the electrochemical signal, as well as hemorrhage and hypotension, suggesting that the level of extracellular 3,4-dihydroxyphenylacetic acid is a good biochemical index of the C1 adrenergic cellular activity in baseline conditions and during cellular activation.

Intra-specific variation in the photosynthetic responses of cyanobiont lichens from contrasting habitats.

The photosynthetic properties of cyanobiont lichens from contrasting habitats were measured to identify whether the increased assimilation rates which characterized Peltigera membranacea (Ach.) Nyl. from an exposed habitat were correlated with increased carbon-concentrating mechanism (CCM) activity. The results were contrasted with data obtained from two populations of Peltigera praetextata (Flörke ex Sommerf.) Zopf collected from dry and damp microhabitats within a shaded woodland and Peltigera leucophlebia (Nyl.) Gyelnik, which has been shown to lack a carbon-concentrating mechanism. The differences in assimilation rates between the cyanobiont lichens were not accounted for by differences in chlorophyll content. Peltigera membranacea from the exposed habitat which had the highest assimilation rates had the lowest Gamma; and K0·5 values and accumulated the greatest Ci -pool indicating that increased Ci accumulation contributed towards the higher assimilation rates shown by these species. The convexity of the light response curve for the cyanobiont lichens decreased with increasing assimilation rates. This might have indicated a diversion of electron transport to energize the carbon-concentrating mechanism. The apparent quantum efficiency of CO2 assimilation (ΦCO2 ) was correlated with the genus of lichen photobiont. All cyanobiont lichens had comparable values for ΦCO2 which were greater than that of the tripartite Peltigera leucophlebia. Light compensation points reflected the exposure of the habitats with higher compensation points characterizing the cyanobiont population from the exposed crag and the tri-partite population from the open grassland. Carbon isotope discrimination values for organic matter and measured instantaneously were the same for all cyanobiont lichens and were comparable with values recorded for species with a carbon-concentrating mechanism. Carbon isotope measurements for P. leucophlebia were typical of those recorded for species without a carbon-concentrating mechanism. Variation in source isotope signature and refixation of respiratory CO2 were considered to be significant factors in determining organic matter and instantaneous carbon-isotope discrimination. These factors might have masked any subtle variation in carbon-isotope discrimination which resulted from variable CCM activity. The functional significance of increased carbon-concentrating mechanism activity in cyanobiont lichens occupying exposed habitats is discussed.

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.

Continuous volume infusion improves circulatory stability in anesthesized rats.

'Optimized' management (OM) was provided to chloralose-anesthetized rats for 12 h by combining continuous infusion (7 ml.kg-1). mechanical ventilation and strict control of acid-base equilibrium (n = 7). The chloralose-anesthetized rats managed conventionally (conventional management: CM, n = 9) received neither volume infusion, nor mechanical ventilation, nor correction of acid-base disturbances. All the OM rats completed the study while 6 out of 9 CM rats died before the end of the study period. Mean arterial pressure (MAP) remained at 100 mmHg for 12 h in the OM group. MAP stayed close to 70 mmHg in the CM group for 6 h and declined to very low levels thereafter (mean +/- S.E.M.: 46.0 +/- 3.9 mmHg at 12 h, P less than 10(-4) when compared to the other group). Central venous pressure and cardiac output remained close to baseline values for 12 h in the OM group. Acid-base equilibrium was preserved in the OM group in contrast to a severe metabolic acidosis in the CM group (pH = 7.14 +/- 0.03 at 12 h; P less than 10(-4). Such as 'optimized' management involving mechanical ventilation with oxygen, continuous infusion and acid-base monitoring may be of value to maintain circulatory stability in anesthetized rodent preparations during long periods of time, as in neurophysiological experiments.

Changes in catecholamine metabolism in the rostral ventrolateral medulla following halothane and nitroprusside-induced hypotension: an in vivo electrochemical study.

The objective was to observe changes in rostral ventrolateral medulla (RVLM) catecholamine metabolism using in vivo voltammetry following induced hypotension with halothane or nitroprusside (SNP). Rats anesthetized (halothane, metocurine) and ventilated were stereotaxically implanted with carbon microelectrodes in the RVLM. The catechol oxidation current (CA.OC, % baseline) was used as an index of RVLM catecholaminergic metabolism. Groups of rats (n = 5) were given (A) halothane 0.75% for 60 min; (B) halothane 2.75% plus phenylephrine infusion to maintain mean arterial pressure (MAP) for 30 min, then halothane 0.75% for 30 min; (C) halothane (2.5-3.0%) for 30 min (MAP 60 +/- 5 mmHg) then halothane 0.75% for 30 min; (D) halothane 0.75% and sodium nitroprusside (SNP) for 30 min (MAP 60 +/- 5 mmHg), then halothane 0.75% for 30 min. Halothane 0.75% produced no significant change in CA.OC or MAP (A), while halothane 2.5-3.0% produced a significant decrease in MAP and a symmetrical significant increase in CA.OC (ANOVA, P less than 0.5). This increase peaked at 30 min (180 +/- 28%) and reached 110 +/- 9% baseline at 60 min. The halothane and phenylephrine combination produced no significant change in CA.OC or MAP during the 30 min exposure (B). SNP (D) produced a significant increase in CA.OC (peak 48 min, 224 +/- 35%) which remained elevated at 60 min (198 +/- 32%). Thus, the induced hypotension produced activation of RVLM catecholaminergic neurons. SNP induced a prolonged significant increase in RVLM catecholamine metabolism which may relate to rebound hypertension following use of this drug.

Clonidine modulates the ventrolateral medullary catechol metabolic hyperactivity induced by hypotension.

In vivo electrochemistry allowed recording of a catechol oxidation current in the ventrolateral medulla, caudal to the obex, in anesthetized rats whose ventilatory, metabolic and hemodynamic parameters were rigorously controlled. Hemorrhage or controlled hypotension induced an increase in the metabolism of catecholamines in the A1 noradrenergic group, which remained activated after full hemodynamic recovery. Clonidine (200 micrograms.kg-1 i.p.) given 30 min prior to hemorrhage or immediately before controlled hypotension suppressed partially the increased metabolism of catecholamines especially during the recovery period. This suggests that clonidine preserved phasic reactivity upon circulatory disturbances and decreased tonic hyperactivity following circulatory recovery.

Baroreflex-linked variations of catecholamine metabolism in the caudal ventrolateral medulla: an in vivo electrochemical study.

In vivo electrochemical recordings of the metabolism of catecholamines were obtained in the caudal ventrolateral medulla in anesthetized rats submitted to various experimental changes in systemic arterial pressure. Hypertension induced with phenylephrine and reversal of hypovolemia decreased the catechol metabolic activity. In contrast, controlled or hypovolemic hypotension, induced respectively with sodium nitroprusside or blood withdrawal (30% of blood volume), reversibly elicited the opposite pattern. This was suppressed by deafferentation. The changes in catechol metabolic activity in response to hypovolemia were accompanied by similar trends of variations of plasma vasopressin levels. By contrast with the increased catechol metabolic activity secondary to hypotension induced by either prazosin, sodium nitroprusside or hypovolemia, clonidine elicited a decrease in catechol metabolic activity. These data show a dynamic and specific involvement of the metabolism of catecholamines themselves promoted by changes in systemic arterial pressure. This pattern of functioning of catechol metabolism in the caudal ventrolateral medulla appears to be negatively related to systemic arterial pressure changes, a finding which does not fit with the proposed vasodepressor role of the A1-group.

Respiratory impairment in inflammatory bowel disease: does it vary with disease activity?

Serial assessments of respiratory function were made in 44 patients with inflammatory bowel disease. Pulmonary function tests were performed at the initial assessment and after three months to see if abnormality was associated with alteration in disease activity, drug therapy or with evidence of immunological disturbance. Fourteen patients (32%) had some abnormality of respiratory function when first investigated. Seven (16%) had a reduced gas transfer factor but these abnormalities were not related to disease activity, drug therapy or any immunological variable. Elevation of both functional residual capacity and residual volume was found in nine (20%) patients at the initial assessment. These abnormalities appeared to be associated with active inflammatory bowel disease and in four of these patients lung volumes returned to normal at 3 months when the bowel disease was in remission.

Determinants of isotopic coupling of CO2 and water vapour within a Quercus petraea forest canopy.

Concentration and isotopic composition (δ13C and δ18O) of ambient CO2 and water vapour were determined within a Quercus petraea canopy, Northumberland, UK. From continuous measurements made across a 36-h period from three heights within the forest canopy, we generated mixing lines (Keeling plots) for δa13CO2, δa C18O16O and δa H218O, to derive the isotopic composition of the signal being released from forest to atmosphere. These were compared directly with measurements of different respective pools within the forest system, i.e. δ13C of organic matter input for δa13CO2, δ18O of exchangeable water for δa C18O16O and transpired water vapour for δa H218O. [CO2] and δa13CO2 showed strong coupling, where the released CO2 was, on average, 4 per mil enriched compared to the organic matter of plant material in the system, suggesting either fractionation of organic material before eventual release as soil-respired CO2, or temporal differences in ecosystem discrimination. δa C18O16O was less well coupled to [CO2], probably due to the heterogeneity and transient nature of water pools (soil, leaf and moss) within the forest. Similarly, δa H218O was less coupled to [H2O], again reflecting the transient nature of water transpired to the forest, seen as uncoupling during times of large changes in vapour pressure deficit. The δ18O of transpired water vapour, inferred from both mixing lines at the canopy scale and direct measurement at the leaf level, approximated that of source water, confirming that an isotopic steady state held for the forest integrated over the daily cycle. This demonstrates that isotopic coupling of CO2 and water vapour within a forest canopy will depend on absolute differences in the isotopic composition of the respective pools involved in exchange and on the stability of each of these pools with time.

Multidrug-resistant tuberculosis in an HIV-positive man in the United Kingdom.

Multidrug-resistant Mycobacterium tuberculosis infection (MDR-TB) in those who are HIV positive has until now been largely a North American phenomenon. We report a fatal case in London.