A mycotic aneurysm related to Salmonella Rissen infection: a case report.

Background: Salmonella species commonly causes infection in humans and on occasion leads to serious complications, such as mycotic aneurysms. Here, we present the first case reported of a patient with a mycotic aneurysm likely secondary to Salmonella Rissen infection.

Case Presentation: The patient presented with 4 weeks of lower back pain, chills and a single episode of diarrhoea 2 months prior during a 14-day trip to Hong Kong and Taiwan.

Regressing Eruptive Disseminated Spitz Nevi.

The eruptive disseminated form of Spitz nevi (EDSN) is the rarest variant, is cosmetically disabling, and has a poorly documented natural history. We report the case of a 4-year-old boy with more than 100 Spitz nevi that have significantly regressed 8 years after onset. There is no satisfactory treatment for EDSN.

The genome of the sparganosis tapeworm Spirometra erinaceieuropaei isolated from the biopsy of a migrating brain lesion.

Background: Sparganosis is an infection with a larval Diphyllobothriidea tapeworm. From a rare cerebral case presented at a clinic in the UK, DNA was recovered from a biopsy sample and used to determine the causative species as Spirometra erinaceieuropaei through sequencing of the cox1 gene. From the same DNA, we have produced a draft genome, the first of its kind for this species, and used it to perform a comparative genomics analysis and to investigate known and potential tapeworm drug targets in this tapeworm.

A multinational outbreak of histoplasmosis following a biology field trip in the Ugandan rainforest.

Background: Outbreaks of histoplasmosis have been increasingly reported in association with travel to endemic areas. Multiple outbreaks have been reported following travel to the Americas, but reports of pulmonary histoplasmosis in short-term immunocompetent travelers to Africa are rare.

Methods: A biology student was referred to our unit with suspected pulmonary histoplasmosis following her return from a field trip in the Ugandan rainforest.

Mortality in Clostridium difficile infection: a prospective analysis of risk predictors.

Objectives: To date, the vast majority of studies investigating risk factors for mortality in Clostridium difficile infection (CDI) have been based on retrospective, routinely collected data, and have not specifically tested the capacity of risk factors to predict outcome. We aimed to prospectively evaluate predictors of mortality in patients with CDI, utilizing established metrics of risk prediction to assess their ability to prognosticate.

Patients And Methods: We collected a cohort of all patients diagnosed with CDI at Addenbrooke's Hospital in 2010.

Clinical and pharmacogenetic influences on response to hydroxychloroquine in discoid lupus erythematosus: a retrospective cohort study.

The recommended systemic therapy of choice for discoid lupus erythematosus (DLE) is the 4-aminoquinolone antimalarial hydroxychloroquine. There is limited published information on the likelihood of clinical response and, in particular, what factors influence outcome. We conducted a multicenter observational and pharmacogenetic study of 200 patients with DLE treated with hydroxychloroquine.

STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis.

Background: Chronic mucocutaneous candidiasis (CMC) is characterized by susceptibility to candida infection of skin, nails, and mucous membranes. Patients with recessive CMC and autoimmunity have mutations in the autoimmune regulator AIRE. The cause of autosomal dominant CMC is unknown.

Impaired T(H)17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

Background: Accumulating evidence implicates T(H)17 cytokines in protection against Candida species infections, but the clinical relevance is not clear. Chronic mucocutaneous candidiasis (CMC) is a heterogeneous syndrome with the unifying feature of selective susceptibility to chronic candidiasis. Different subgroups with distinct clinical features are recognized, including autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), CMC with hypothyroidism, and isolated CMC.

Differential costimulation through CD137 (4-1BB) restores proliferation of human virus-specific "effector memory" (CD28(-) CD45RA(HI)) CD8(+) T cells.

In healthy carriers of human cytomegalovirus (HCMV), the virus-specific memory CD8(+) T-cell population is often dominated by CD28(-) CD45RA(hi) cells that exhibit direct ex vivo cytotoxicity but whose capacity for proliferation and generation of further memory cells has been questioned. We show that when highly purified CD28(-) CD45RA(hi) CD8(+) T cells are stimulated with viral peptide presented by autologous monocytes, the virus-specific T cells show early up-regulation of CD137 (4-1BB) and CD278 (ICOS), re-express CD28, and proliferate with similarly high cloning efficiency in limiting dilution analysis as CD28(+) CD45RO(hi) cells or CD28(-) CD45RO(hi) cells. Using peptide-pulsed autologous fibroblasts transfected with individual costimulatory ligands as antigen presenting cells, we showed CD137L to be a key costimulatory ligand for proliferation of CD28(-) CD45RA(hi) CD8(+) T cells and not CD80, CD86, or CD275 (ICOSL).

Rapid CD8+ T cell repertoire focusing and selection of high-affinity clones into memory following primary infection with a persistent human virus: human cytomegalovirus.

To investigate the mechanism of selection of individual human CD8+ T cell clones into long-term memory following primary infection with a persistent human virus (human CMV (HCMV)), we undertook a longitudinal analysis of the diversity of T cell clones directed toward an immunodominant viral epitope: we followed this longitudinally from early T cell expansion through the contraction phase and selection into the memory pool. We show that following initial HCMV infection, the early primary response against a defined epitope was composed of diverse clones possessing many different TCR Vbeta segments. Longitudinal analysis showed that this usage rapidly focused predominantly on a single TCR Vbeta segment within which dominant clones frequently had public TCR usage, in contrast to subdominant or contracted clones.

Large HIV-specific CD8 cytotoxic T-lymphocyte (CTL) clones reduce their overall size but maintain high frequencies of memory CTL following highly active antiretroviral therapy.

Cytotoxic T-lymphocytes (CTL) play an important role in the control of human immunodeficiency virus (HIV) and of human cytomegalovirus (HCMV) infection. Following highly active antiretroviral therapy (HAART), most studies have demonstrated a decline in the frequency of HIV-specific CTL. We analysed the effect of HAART on the size, phenotype and function of individual HIV- and HCMV-specific CTL clones, using clonotypic oligonucleotide probing specific for the T-cell receptor (TCR) beta-chain hypervariable sequence of defined immunodominant CTL clones specific for peptides of HIV or HCMV, and quantified the limiting dilution analysis frequencies of CTL precursors (CTLp) specific for the same viral peptides.

Long-term stable expanded human CD4+ T cell clones specific for human cytomegalovirus are distributed in both CD45RAhigh and CD45ROhigh populations.

T cells play an important role in the control of human CMV (HCMV) infection. Peripheral blood CD4+ T cell proliferative responses to the HCMV lower tegument protein pp65 have been detected in most healthy HCMV carriers. To analyze the clonal composition of the CD4+ T cell response against HCMV pp65, we characterized three MHC class II-restricted peptide epitopes within pp65 in virus carriers.

Autoimmune inflammatory disorders, systemic corticosteroids and pneumocystis pneumonia: a strategy for prevention.

Background: Pneumocystis pneumonia (PCP) is an increasing problem amongst patients on immunosuppression with autoimmune inflammatory disorders (AID). The disease presents acutely and its diagnosis requires bronchoalveolar lavage in most cases. Despite treatment with intravenous antibiotics, PCP carries a worse prognosis in AID patients than HIV positive patients.

Human cytomegalovirus-specific immunity following haemopoietic stem cell transplantation.

The herpesvirus Human Cytomegalovirus (HCMV) is an important opportunistic infection in recipients of allogeneic haemopoietic stem cell transplants, in whom HCMV-specific CD8+ and CD4+ T-cell responses are impaired. The nature of the HCMV-specific T-cell response in healthy virus carriers has been characterised in detail. High frequencies of circulating CD8+ T-cells that recognise defined viral peptides are maintained for years, and include individual CD8+ clones that have undergone extensive clonal expansion and phenotypic diversification in vivo.

Late diversification in the clonal composition of human cytomegalovirus-specific CD8+ T cells following allogeneic hemopoietic stem cell transplantation.

To investigate the mechanisms of human T-cell reconstitution following allogeneic hemopoietic stem cell transplantation (alloSCT), we analyzed the clonal composition of human cytomegalovirus (HCMV)-specific or Epstein-Barr virus (EBV)-specific CD8+ T cells in 10 alloSC transplant recipients and their donors. All virus-specific CD8+ T-cell clones isolated from recipients after alloSCT contained DNA of donor origin. In all 6 D+/R+ sibling alloSCTs from seropositive donors into seropositive recipients, donor virus-specific clones transferred in the allograft underwent early expansion and were maintained long term in the recipient.

Treatment of pruritus associated with systemic disorders in the elderly: a review of the role of new therapies.

Generalised pruritus is common in the elderly. Idiopathic 'senile pruritus' is a diagnosis of exclusion, and an underlying systemic disorder should be sought. Thyroid disease, haematological malignancy, iron deficiency, cholestasis or renal impairment may be responsible for pruritus.

Identification of naive or antigen-experienced human CD8(+) T cells by expression of costimulation and chemokine receptors: analysis of the human cytomegalovirus-specific CD8(+) T cell response.

Human CMV (HCMV) infection provides an informative model of how long term human CD8(+) T cell memory is maintained in the presence of Ag. To clarify the phenotypic identity of Ag-experienced human CD8(+) T cells in vivo, we determined the expression of costimulation and chemokine receptors on Ag-specific CD8(+) T cells by quantifying individual virus-specific clones in different cell populations using TCR clonotypic probing. In healthy HCMV carriers, expanded CD8(+) clones specific for either HCMV tegument protein pp65 or immediate-early protein IE72 are found in both CD45RO(high) cells and the subpopulation of CD45RA(high) cells that lack the costimulatory molecule CD28.