[Acquired angioedema due to C1-inhibitor deficiency: CREAK recommendations for diagnosis and treatment]. / Angiœdèmes par déficit acquis en C1-inhibiteur : recommandations du CREAK pour le diagnostic et la prise en charge.

Acquired angioedema with C1-inhibitor deficiency is a rare and peculiar entity belonging to the spectrum of bradykinin angioedemas. It usually occurs in subjects over 60 years old, and is mostly associated with a B-cell lymphoid hemopathy or a monoclonal gammopathy. The diagnosis relies on at least one angioedema episode, lasting more than 24 h, and on the decrease of functional C1-inhibitor. Low C1q is observed in 90% of patients, and an anti C1-inhibitor antibody is found in 50% of patients. The treatment of severe attacks relies on icatibant or C1-inhibitor perfusions. Long term prophylaxis in patients with frequent attacks requires treatment of the associated hemopathy if so. In case of idiopathic angioedema, tranexamic acid and danazol may be used, provided that there is-no thrombophilia; as well as rituximab as second-line treatment. Inhibitors of kallikrein still need to be evaluated in this therapeutic indication.

Fungal Planet description sheets: 716-784.

Novel species of fungi described in this study include those from various countries as follows: Australia, Chaetopsina eucalypti on Eucalyptus leaf litter, Colletotrichum cobbittiense from Cordyline stricta × C. australis hybrid, Cyanodermella banksiae on Banksia ericifolia subsp. macrantha, Discosia macrozamiae on Macrozamia miquelii, Elsinoë banksiigena on Banksia marginata, Elsinoë elaeocarpi on Elaeocarpus sp., Elsinoë leucopogonis on Leucopogon sp., Helminthosporium livistonae on Livistona australis, Idriellomyces eucalypti (incl. Idriellomyces gen. nov.) on Eucalyptus obliqua, Lareunionomyces eucalypti on Eucalyptus sp., Myrotheciomyces corymbiae (incl. Myrotheciomyces gen. nov., Myrotheciomycetaceae fam. nov.), Neolauriomyces eucalypti (incl. Neolauriomyces gen. nov., Neolauriomycetaceae fam. nov.) on Eucalyptus sp., Nullicamyces eucalypti (incl. Nullicamyces gen. nov.) on Eucalyptus leaf litter, Oidiodendron eucalypti on Eucalyptus maidenii, Paracladophialophora cyperacearum (incl. Paracladophialophoraceae fam. nov.) and Periconia cyperacearum on leaves of Cyperaceae, Porodiplodia livistonae (incl. Porodiplodia gen. nov., Porodiplodiaceae fam. nov.) on Livistona australis, Sporidesmium melaleucae (incl. Sporidesmiales ord. nov.) on Melaleuca sp., Teratosphaeria sieberi on Eucalyptus sieberi, Thecaphora australiensis in capsules of a variant of Oxalis exilis. Brazil, Aspergillus serratalhadensis from soil, Diaporthe pseudoinconspicua from Poincianella pyramidalis, Fomitiporella pertenuis on dead wood, Geastrum magnosporum on soil, Marquesius aquaticus (incl. Marquesius gen. nov.) from submerged decaying twig and leaves of unidentified plant, Mastigosporella pigmentata from leaves of Qualea parviflorae, Mucor souzae from soil, Mycocalia aquaphila on decaying wood from tidal detritus, Preussia citrullina as endophyte from leaves of Citrullus lanatus, Queiroziella brasiliensis (incl. Queiroziella gen. nov.) as epiphytic yeast on leaves of Portea leptantha, Quixadomyces cearensis (incl. Quixadomyces gen. nov.) on decaying bark, Xylophallus clavatus on rotten wood. Canada, Didymella cari on Carum carvi and Coriandrum sativum. Chile, Araucasphaeria foliorum (incl. Araucasphaeria gen. nov.) on Araucaria araucana, Aspergillus tumidus from soil, Lomentospora valparaisensis from soil. Colombia, Corynespora pseudocassiicola on Byrsonima sp., Eucalyptostroma eucalyptorum on Eucalyptus pellita, Neometulocladosporiella eucalypti (incl. Neometulocladosporiella gen. nov.) on Eucalyptus grandis × urophylla, Tracylla eucalypti (incl. Tracyllaceae fam. nov., Tracyllalales ord. nov.) on Eucalyptus urophylla. Cyprus, Gyromitra anthracobia (incl. Gyromitra subg. Pseudoverpa) on burned soil. Czech Republic, Lecanicillium restrictum from the surface of the wooden barrel, Lecanicillium testudineum from scales of Trachemys scripta elegans. Ecuador, Entoloma yanacolor and Saproamanita quitensis on soil. France, Lentithecium carbonneanum from submerged decorticated Populus branch. Hungary, Pleuromyces hungaricus (incl. Pleuromyces gen. nov.) from a large Fagus sylvatica log. Iran, Zymoseptoria crescenta on Aegilops triuncialis. Malaysia, Ochroconis musicola on Musa sp. Mexico, Cladosporium michoacanense from soil. New Zealand , Acrodontium metrosideri on Metrosideros excelsa, Polynema podocarpi on Podocarpus totara, Pseudoarthrographis phlogis (incl. Pseudoarthrographis gen. nov.) on Phlox subulata. Nigeria, Coprinopsis afrocinerea on soil. Pakistan, Russula mansehraensis on soil under Pinus roxburghii. Russia, Baorangia alexandri on soil in deciduous forests with Quercus mongolica. South Africa, Didymocyrtis brachylaenae on Brachylaena discolor. Spain, Alfaria dactylis from fruit of Phoenix dactylifera, Dothiora infuscans from a blackened wall, Exophiala nidicola from the nest of an unidentified bird, Matsushimaea monilioides from soil, Terfezia morenoi on soil. United Arab Emirates, Tirmania honrubiae on soil. USA, Arxotrichum wyomingense (incl. Arxotrichum gen. nov.) from soil, Hongkongmyces snookiorum from submerged detritus from a fresh water fen, Leratiomyces tesquorum from soil, Talaromyces tabacinus on leaves of Nicotiana tabacum. Vietnam, Afroboletus vietnamensis on soil in an evergreen tropical forest, Colletotrichum condaoense from Ipomoea pes-caprae. Morphological and culture characteristics along with DNA barcodes are provided.

New species from Phytophthora Clade 6a: evidence for recent radiation.

During routine vegetation health surveys in the southwest of Western Australia (SWWA), several Phytophthora isolates with affinity to Clade 6a have been recovered. In this study, all known taxa from Clade 6a, P. inundata, P. humicola, P. gemini, P. 'walnut' and P. 'personii', and the new isolates were compared based on morphology and DNA sequence data from three nuclear genes and two mitochondrial genes resulting in the description of five new species, P. balyanboodja, P. condilina, P. cooljarloo, P. kwongonina and P. pseudorosacearum. With the exception of P. gemini and P. humicola, all species from Clade 6a have been recovered from natural ecosystems in SWWA. These species are morphologically similar, with predominantly ovoid sporangia and nested and extended internal proliferation. If oospores are present, they tend to be aplerotic with paragynous antheridia mostly attached adjacent to the oogonial stalk. They can all grow at 35 °C and have a fast growth rate on most agar media. These species have all been recovered from the rhizosphere soil and dead and dying plants within dry kwongon heathlands, often from water gaining sites and frequently from very isolated areas. The radiation, origin and potential ecological role of these species are discussed.

[Evolution of the carboxyhemoglobinemia and methemoglobinemia during endoscopic resection: An observational study]. / Évolution de la carboxyhémoglobinémie et de la méthémoglobinémie lors de résections endoscopiques : une étude observationnelle.

AIM OF THE STUDY: Combustion of organic tissues due to endoscopic resection could induce methemoglobin (MetHb) and carboxyhemoglobin (COHb) formation. The aim of this study is to evaluate MetHb and COHb formation in patients undergoing prostatic or bladder endoscopic procedures. METHODS: COHb and MetHb measurements were performed in 44 patients at the beginning and end of the procedure. A third measurement was done in patients who stayed more than one hour in the recovery room. Means were compared using Student t-test, simple regressions were used for quantitative variables and ANOVA for categorical variables. Multiple linear regressions were used for multivariate analysis. RESULTS: COHb increased by 0.5±0.9 % (95 % CI: 0.2 to 0.7 % P=0.001). MetHb increase was 0.0±0.4 % (95 % CI: -0.1 to 0.2 % P=0.552). In univariate analysis, the variables associated with COHb increase are the length of surgery, the amount of irrigation fluid and location (prostate or bladder) of the procedure. In the multivariate model, COHb increase is associated with the amount of liquid and the location. CONCLUSION: MetHb did not increase during endoscopic surgery. In contrast, COHb increases, and can, in some patients, exceed 2-4 %. This could be responsible for a decreased angina threshold in patients with ischemic heart disease. LEVEL OF EVIDENCE: 4.

Fungal Planet description sheets: 400-468.

Novel species of fungi described in the present study include the following from Australia: Vermiculariopsiella eucalypti, Mulderomyces natalis (incl. Mulderomyces gen. nov.), Fusicladium paraamoenum, Neotrimmatostroma paraexcentricum, and Pseudophloeospora eucalyptorum on leaves of Eucalyptus spp., Anungitea grevilleae (on leaves of Grevillea sp.), Pyrenochaeta acaciae (on leaves of Acacia sp.), and Brunneocarpos banksiae (incl. Brunneocarpos gen. nov.) on cones of Banksia attenuata. Novel foliicolous taxa from South Africa include Neosulcatispora strelitziae (on Strelitzia nicolai), Colletotrichum ledebouriae (on Ledebouria floridunda), Cylindrosympodioides brabejum (incl. Cylindrosympodioides gen. nov.) on Brabejum stellatifolium, Sclerostagonospora ericae (on Erica sp.), Setophoma cyperi (on Cyperus sphaerocephala), and Phaeosphaeria breonadiae (on Breonadia microcephala). Novelties described from Robben Island (South Africa) include Wojnowiciella cissampeli and Diaporthe cissampeli (both on Cissampelos capensis), Phaeotheca salicorniae (on Salicornia meyeriana), Paracylindrocarpon aloicola (incl. Paracylindrocarpon gen. nov.) on Aloe sp., and Libertasomyces myopori (incl. Libertasomyces gen. nov.) on Myoporum serratum. Several novelties are recorded from La Réunion (France), namely Phaeosphaeriopsis agapanthi (on Agapanthus sp.), Roussoella solani (on Solanum mauritianum), Vermiculariopsiella acaciae (on Acacia heterophylla), Dothiorella acacicola (on Acacia mearnsii), Chalara clidemiae (on Clidemia hirta), Cytospora tibouchinae (on Tibouchina semidecandra), Diaporthe ocoteae (on Ocotea obtusata), Castanediella eucalypticola, Phaeophleospora eucalypticola and Fusicladium eucalypticola (on Eucalyptus robusta), Lareunionomyces syzygii (incl. Lareunionomyces gen. nov.) and Parawiesneriomyces syzygii (incl. Parawiesneriomyces gen. nov.) on leaves of Syzygium jambos. Novel taxa from the USA include Meristemomyces arctostaphylos (on Arctostaphylos patula), Ochroconis dracaenae (on Dracaena reflexa), Rasamsonia columbiensis (air of a hotel conference room), Paecilomyces tabacinus (on Nicotiana tabacum), Toxicocladosporium hominis (from human broncoalveolar lavage fluid), Nothophoma macrospora (from respiratory secretion of a patient with pneumonia), and Penidiellopsis radicularis (incl. Penidiellopsis gen. nov.) from a human nail. Novel taxa described from Malaysia include Prosopidicola albizziae (on Albizzia falcataria), Proxipyricularia asari (on Asarum sp.), Diaporthe passifloricola (on Passiflora foetida), Paramycoleptodiscus albizziae (incl. Paramycoleptodiscus gen. nov.) on Albizzia falcataria, and Malaysiasca phaii (incl. Malaysiasca gen. nov.) on Phaius reflexipetalus. Two species are newly described from human patients in the Czech Republic, namely Microascus longicollis (from toenails of patient with suspected onychomycosis), and Chrysosporium echinulatum (from sole skin of patient). Furthermore, Alternaria quercicola is described on leaves of Quercus brantii (Iran), Stemphylium beticola on leaves of Beta vulgaris (The Netherlands), Scleroderma capeverdeanum on soil (Cape Verde Islands), Scleroderma dunensis on soil, and Blastobotrys meliponae from bee honey (Brazil), Ganoderma mbrekobenum on angiosperms (Ghana), Geoglossum raitviirii and Entoloma kruticianum on soil (Russia), Priceomyces vitoshaensis on Pterostichus melas (Carabidae) (Bulgaria) is the only one for which the family is listed, Ganoderma ecuadoriense on decaying wood (Ecuador), Thyrostroma cornicola on Cornus officinalis (Korea), Cercophora vinosa on decorticated branch of Salix sp. (France), Coprinus pinetorum, Coprinus littoralis and Xerocomellus poederi on soil (Spain). Two new genera from Colombia include Helminthosporiella and Uwemyces on leaves of Elaeis oleifera. Two species are described from India, namely Russula intervenosa (ectomycorrhizal with Shorea robusta), and Crinipellis odorata (on bark of Mytragyna parviflora). Novelties from Thailand include Cyphellophora gamsii (on leaf litter), Pisolithus aureosericeus and Corynascus citrinus (on soil). Two species are newly described from Citrus in Italy, namely Dendryphiella paravinosa on Citrus sinensis, and Ramularia citricola on Citrus floridana. Morphological and culture characteristics along with ITS nrDNA barcodes are provided for all taxa.

Assessing psychological well-being: a holistic investigation of NHS employees.

A substantial body of research has investigated the effects of work on the psychological well-being of employees. However, there has been little assessment of the ways in which workplace factors (such as job demands, working conditions, inter-personal relations and workplace change) interact with personal factors (such as work-life balance, family circumstances, key personality traits or demographic characteristics) to affect psychological health. This article reports findings from a study which aimed to construct and test a comprehensive model of the influences on employee well-being within the UK National Health Service (NHS). The results show that psychological well-being is influenced by a complex array of personal, environmental and work factors. A key finding is that there are clear associations between workplace change and well-being and between work-life (im)balance and well-being. These effects appear to be independent of one another and therefore require separate attention from managers and employers.

6-tioguanine monitoring in steroid-dependent patients with inflammatory bowel diseases receiving azathioprine.

BACKGROUND: 6-Thioguanine (6-tioguanine) nucleotides are the active metabolites of azathioprine. AIM: The aim of the study was to evaluate the rate of clinical remission without steroids in steroid-dependent Crohn's disease and ulcerative colitis patients receiving azathioprine, the medium- and long-term efficacy and the predictive factors of clinical response when monitoring 6-tioguanine. METHODS: Steroid-dependent Crohn's disease and ulcerative colitis patients receiving either azathioprine or not (treated later with a daily dose of 2.5 mg/kg) were prospectively included. 6-tioguanine was monitored at 1 and 2 months and every 3 months thereafter for 1 year. The azathioprine dose was adapted to reach a 6-tioguanine level of >250 pmol/8 x 10(8) red blood cells. Thiopurine methyltransferase genotype/phenotype was evaluated in some patients. RESULTS: A total of 106 patients were prospectively included (70 Crohn's disease, 36 ulcerative colitis). The clinical remission rate without steroids in patients receiving azathioprine, in intention-to-treat analysis, was 72% and 59% at 6 and 12 months, respectively. The remission rate was significantly higher in patients with 6-tioguanine >250 pmol/8 x 10(8) RBC (86% and 69% at 6 and 12 months, respectively; P < 0.01). No significant difference was observed between Crohn's disease and ulcerative colitis patients whether treated by azathioprine or not on inclusion. In the univariate analysis, the absence of Crohn's disease stenosis, a 6-tioguanine level >250 pmol/8 x 10(8) RBC, and an increase of erythrocyte mean corpuscular volume were the factors predictive of a favourable clinical response. In the multivariate analysis, only a 6-tioguanine level of >250 pmol/8 x 10(8) red blood cells was a predictive factor of favourable clinical remission. CONCLUSIONS: Clinical remission without steroids is significantly more likely when monitoring 6-tioguanine so as to reach a level of >250 pmol/8 x 10(8) red blood cells in steroid-dependent Crohn's disease and ulcerative colitis patients receiving azathioprine (86% and 69% at 6 and 12 months, respectively).

5-lipoxygenase expression and activity in aorta from streptozotocin-induced diabetic rats.

We previously reported an activation of the 5-lipoxygenase pathway in aorta from streptozotocin-induced diabetic rats. The aim of this study was to investigate whether this activation was associated with an increased expression of 5-lipoxygenase, an increased cysteinyl leukotriene (CysLT) production in response to arachidonic acid or calcium ionophore A23187 and/or a hypersensitivity of the aorta to CysLTs in streptozotocin-induced diabetic rats. In aorta from diabetic and control rats, reverse transcriptase-PCR and western blot analysis with a specific 5-lipoxygenase antibody provided evidence for the presence of 5-lipoxygenase in aorta. However, the expression of 5-lipoxygenase was not significantly different between diabetic and control rats. Challenge by A23187 (10 microM) and arachidonic acid (10 microM and 0.1 mM) with or without A23187 (10 micromol/l) induced a significant increase of CysLT release (measured by enzyme immunoassay) that was in the same range in aorta from control and diabetic rats. In contrast, aortas from diabetic rats showed a greater sensitivity to LTC4 and LTD4 contractile effects. These data suggested that the activation of the 5-lipoxygenase pathway previously reported in streptozotocin-induced diabetic rats could be explained by an augmented sensitivity to CysLTs of the diabetic aorta.

[Leukotrienes and 12-HETE: key mediators of angiotensin II-mediated vascular effects.Rol in hypertension]. / Leucotriènes et 12-HETE: modulateurs des effets vasculaires de l'angiotensine II. Implication dans l'hypertension artérielle.

Arachidonic acid metabolism-derived products are key mediators of angiotensin II-mediated vascular effects. The modulatory effect of cyclooxygenase derived products--in particular thromboxane A2 and prostaglandin H2--in angiotensin II-mediated vascular effects is well established. In contrast, few studies have assessed the involvement of lipoxygenase-derived products in the vascular effects of angiotensin II. Cysteinyl leukotrienes (5-lipoxygenase-derived products) and 12-hydroxyeicosatetraenoic acids (12-HETE) (12-lipoxygenase-derived products) are potent proinflammatory and vasomotor mediators. Their biosynthesis is increased in various models of hypertension. In addition, compelling evidence has suggested that they might contribute to the vasoconstrictor, hypertrophic and mitogenic effects of angiotensin II. The demonstration of their contribution to angiotensin II-mediated vascular effects may explain, at least in part, the vascular inflammatory complications associated with hypertension.

Cysteinyl leukotrienes modulate angiotensin II constrictor effects on aortas from streptozotocin-induced diabetic rats.

Angiotensin II (Ang II) is a vasopressor peptide involved in the pathogenesis of cardiovascular diseases associated with diabetes mellitus. We have previously reported that the 5-lipoxygenase-derived products, particularly the cysteinyl leukotrienes (CysLTs), are involved in Ang II-induced contraction. In this study, we demonstrated that CysLTs contribute to the contraction elicited by Ang II in isolated aortas from streptozotocin-induced diabetic (SS) rats but not from insulin-treated diabetic rats, fructose-fed rats, or control rats. In an organ bath, pretreatment with the 5-lipoxygenase inhibitor (AA861, 10 micromol/L) reduced by 37.6+/-8.2% and 30.1+/-10.9% the Ang II-induced contractions in intact and endothelium-denuded aortic rings, respectively, from SS rats. In contrast, the CysLT(1) receptor antagonist (MK571, 1 micromol/L) or the dual CysLT(1)/CysLT(2) receptor antagonist (BAY-u9773, 0.1 micromol/L) did not affect Ang II-induced contraction. In addition, Ang II induced a 6.2+/-1.5-fold increase in CysLT release through the stimulation of the Ang II type 1 receptor. Furthermore, the urinary excretion of leukotriene E(4) was increased in SS rats (leukotriene E(4), 13.7+/-2.9 ng/24 h [SS rats, n=10] versus 1.5+/-0.5 ng/24 h [control rats, n=6]; P<0.0004). These data suggest the activation of the 5-lipoxygenase pathway in SS rats and the involvement of 5-lipoxygenase-derived products, particularly the CysLTs, in Ang II-induced contraction in aortas from SS rats through stimulation of CysLT receptors different from the well-characterized CysLT(1) or CysLT(2) receptor.

Immune responses and reconstitution in HIV-1 infected individuals: impact of anti-retroviral therapy, cytokines and therapeutic vaccination.

Most patients with chronic HIV-1 infection lack functional CD4(+) and CD8(+) HIV-1-specific T cells with proliferative and cytolytic capacity, respectively. This is despite being able to produce intracellular cytokines in response to viral antigens. Protease inhibitor (PI)-based highly active anti-retroviral therapy (HAART) is unable to completely eradicate virus and fails to enable total restoration of immunity including induction of anti-HIV-1 responses. We have taken novel approaches towards the treatment of chronic HIV-1 disease with the aim of instigating long-term non-progressor status and depletion of virus reservoirs. HIV-1-specific CD4(+) and CD8(+) T cell responses were measured following the administration of cytokines, during therapeutic vaccination, and following treatment interruption (TI) or drug therapy change. Administration of cytokines, with or without therapeutic vaccination, in HAART treated patients, improved both CD4(+) and CD8(+) HIV-1-specific T cell responses even in late-stage disease. Virus-specific T cell responses were also seen during TI or when transient viraemia was apparent, and following therapy change from a PI- to a non-nucleoside-based HAART regimen. Reconstitution of HIV-1-specific immune responses was found to be transient and reversal to the previous anergic state was rapid. Viral reservoirs in the latently infected resting CD4(+) T cells, on follicular dendritic cells of germinal centers or even in infected thymic epithelium may be involved in clonal suppression and anergy. These may present major obstacles to the maintenance of HIV-1-specific responses and the eventual eradication of HIV-1.

Circadian rhythmicity of whole-blood glutathione in healthy subjects.

OBJECTIVES: Physiologic rhythms of antioxidants have been the subject of considerable interest in recent years. Physiologically, it is known that 24-h variability in whole-blood glutathione (GSH) could depend on various factors, such as meal composition, protein dietary content, meal-related hormonal modifications, and stress. Experiments were conducted to determine if the circadian variations previously observed in hepatic concentrations of reduced glutathione in animals also occurred in healthy volunteers. METHODS: The circadian periodicity of whole-blood glutathione was explored. All parameters were measured enzymatically at 4-h intervals over a 24-h period. RESULTS: Circadian rhythms were not found. The rhythms peak for glutathione content occurred at 9 h with a small peak at 21 h. The nadir occurred at 17 h and 1 h. CONCLUSION: These data show that despite this wide distribution of glutathione throughout the day we could not find any significant intertime variability.

Spatial and temporal localisation of bone morphogenetic protein-3 (osteogenin) in the developing rat submandibular gland.

Submandibular gland morphogenesis is a highly regulated process modulated by epithelio-mesenchymal interactions. Bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta (TGF-beta) superfamily, are known to be soluble mediators of epithelio-mesenchymal interactions during the development of certain organs. The aim of this study was to localise bone morphogenetic protein-3 (BMP-3 or osteogenin), spatially and temporally in the developing rat submandibular gland. Immunocytochemistry was performed on sections of the developing submandibular gland (gestation ages E14.5-E19.5). BMP-3 was localised in the extra-cellular matrix of the mesenchyme of the gland in all the stages examined. Intense staining of BMP-3 was observed in the epithelial cells of the developing end-buds between stages E14.5 and E16.5. As cytodifferentiation progressed (stage E17.5 onwards) the number of epithelial cells in the developing acini in which BMP-3 was present became markedly reduced. Similarly, the number of cells containing BMP-3 in the developing ducts decreased as duct development progressed. By stage E19.5, BMP-3 was located mainly in the immature ducts. While the effects of BMP-3 on matrix macromolecules could not be deduced from this study, its spatial and temporal location within the developing glands may indicate a role in the co-ordinated regulation of branching morphogenesis.

Induction of HIV-1-specific T cell responses by administration of cytokines in late-stage patients receiving highly active anti-retroviral therapy.

Highly active anti-retroviral therapy (HAART) is associated with reduction in the morbidity and mortality of patients with advanced HIV-1 disease. The ability of such treatment to improve immune responses against HIV-1 and opportunistic pathogens is variable and limited. Addition of cytokine immunotherapy to this treatment may improve immune responses. IL-2 with or without granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered to HIV-1+ individuals receiving HAART with undetectable viral loads, and CD4 counts < 100 cells/microl. In one patient presenting with Mycobacterium avium complex (MAC) infection, we evaluated the effect of cytokine immunotherapy on lymphocyte phenotype; plasma viral load; proliferative responses to mitogens, recall and HIV-1 antigens; cytokine production and message in response to non-specific and specific stimuli; and natural killer (NK) cell activity. Proliferation assays were performed in two similar patients. Before cytokine immunotherapy the predominant CD8+ population was mainly CD28-. No proliferation or IL-2 production was seen in response to mitogens, recall or HIV-1 antigens; and no HIV-1 peptide-specific interferon-gamma (IFN-gamma)-secreting cells were present. Low levels of IL-4 were detected in response to antigens to which patients had been exposed, associated with up-regulated expression of costimulatory molecules influenced by IL-4. Following IL-2 administration, loss of IL-4 was associated with increased NK cell activity and HIV-1 peptide-specific and non-specific IFN-gamma-producing cells. Proliferative responses associated with IL-2 production and responsiveness were only seen after subsequent concomitant administration of GM-CSF with IL-2. These changes mirrored clinical improvement. An imbalance of lymphocyte subsets may account for immune unresponsiveness when receiving HAART. Restoration of responses following immunotherapy suggests a shift towards a lymphocyte profile with anti-pathogen activity.

GP referrals to adult psychological services: a research agenda for promoting needs-led practice through the involvement of mental health clinicians.

General practitioners' responses to psychological problems presented in the surgery have a significant impact on the care that their patients will receive. Importantly, their referral behaviour has a knock-on effect on the shaping of psychological treatment services. The present paper summarizes the types of influences that impact on GPs' referral decisions and investigates the possible role that mental health clinicians may play in facilitating these processes. GPs' referral decisions are shown to be affected by a large number of factors which fall within the following domains: patients' help-seeking behaviour and their representations of mental ill-health; the ability of GPs to detect psychological disorders; GPs' attitudes towards psychological problems and their management; service criteria for appropriate referral; and links with mental health services. For each of these domains, methods by which mental health clinicians can promote better referral practice are suggested. Recommendations are made for further research into the efficacy and clinical utility of these methods.