Infection with Anaplasma phagocytophilum induces multilineage alterations in hematopoietic progenitor cells and peripheral blood cells.

Infection with Anaplasma phagocytophilum, a gram-negative, lipopolysaccharide (LPS)-negative, obligate intracellular bacterium, results in multiple peripheral blood cytopenias. We hypothesized that infection with this organism would result in decreased bone marrow (BM) function and shifts in hematopoietic progenitor cells (HPCs) and lineage-committed cells in a well-established murine model of infection. HPCs and lineage-committed progenitors were enumerated in the BM and spleen during acute infection. BM cytokine production and BM CXCL12 expression were determined. Infection resulted in peripheral blood bicytopenia, marked decreases in the number of lineage-committed HPCs in the BM along with concurrent increases in the number of lineage-committed HPCs in the spleen, and a mixed, predominantly myelosuppressive BM cytokine environment. There was significant downregulation of CXCL12 in BM cells that may have been partially responsible for changes in HPC trafficking observed. Changes occurred in the absence of direct pathogen infection of BM cells. Hematopoietic lineage assessment demonstrated that there was loss of erythrocytes and B lymphocytes from the BM along with increased granulopoiesis. These changes were accompanied by splenomegaly due to lymphoid hyperplasia and increased hematopoiesis, most notably erythropoiesis. These changes largely mimic well-described inflammation and endotoxin-mediated effects on the BM and spleen; however, the numbers of peripheral blood neutrophils appear to be independently modulated as granulocytic hyperplasia does not result in neutrophilia. Our findings highlight a well-conserved series of events that we demonstrate can be instigated by an LPS-negative pathogen in the absence of an endotoxin-mediated acute proinflammatory response.

Primary patency rates of AV fistulas and the effect of patient variables.

BACKGROUND: DOQI (The Dialysis Outcomes Quality Initiative) recommend 40% of prevalent renal failure patients should be undergoing hemodialysis (HD) using autogenous arteriovenous fistulae (AVF). The aim of this study is to assess the primary patency rates of wrist and elbow fistulae, and to examine how patient variables influence the success of a fistula. In addition, an attempt has been made to address the main issue of survival rates in this high risk patient population. METHODS: A retrospective study was performed on all patients in the University Hospital of North Staffordshire who underwent creation of a wrist or elbow fistula for HD. During the study period 289 primary AVFs were created. In all, 210 AVF were sited at the wrist and 79 at the elbow. Follow-up ranged from 3 months to 4 yrs. Primary patency and patient death, transplant and transfer were taken as end points. Patient survival was defined as time of fistula creation to patient death. Actuarial survival was calculated using Kaplan-Meier survival analyses, with differences between groups determined using log rank analysis, and statistical significance obtained using X2 tests. RESULTS: Primary patency for wrist fistulae was 49, 41 and 32% at 6, 12 and 24 months, respectively, and 57, 51 and 38% for elbow fistulae. Regression analysis showed fistula survival to be significantly greater in males than in females (p=0.023). Fistula survival rates in non-diabetics patients were higher than in patients with diabetes however, this was not significant (p=0.11); (54, 48 and 34% in diabetics compared to 45, 35 and 26% in non-diabetics at 6, 12 and 24 months, respectively). Age did not influence fistula survival; however, it did affect patient survival. Patient survival was 90, 74 and 56% at 1, 2 and 3 yrs, respectively, and in >60s fell to 86, 71 and 50%. Overall 74/245 (30%) patients died. CONCLUSION: These results suggest that overall primary patency rates for wrist and elbow fistulae are comparable to similar studies at 6, 12 and 24 months. Fistula survival after this period is dictated by poor patient survival. Our findings suggest that creation of primary vascular access at the elbow in older females and diabetics may be associated with better results.

Characterisation of whiskeys using solid-phase microextraction with gas chromatography-mass spectrometry.

The application of solid-phase microextraction and gas chromatography-mass spectrometry to the detection of flavour volatiles present in Irish and Scottish whiskeys was investigated. A method was developed to characterise these volatiles which included the extraction, identification and quantification of 17 congeners which included fusel alcohols, acetates and esters. The method validation produced the optimum fibre [85 microm poly(acrylate)], extraction time (35 min), sample volume size (3 ml) and desorption time (5 min). The impact of salt on the absorption process was also studied. Characteristic profiles were determined for each whiskey and the flavour congeners were quantified using 4-methyl-2-pentanol as the internal standard. Calibration ranges were determined for each of the congeners with coefficients of linearity ranging from 0.993 (butan-1-ol) to 0.999 (ethyl laurate) and relative standard deviations ranging from 2.5% (2-methylbutan-1-ol) to 21% (furfural) at a concentration of 18.2 mg/l. Detection limits ranged from 0.1 mg/l (ethyl caprate) to 21 mg/l (butan-2-ol).

Endemic tinea imbricata--a study on Goodenough Island, Papua New Guinea.

Tinea imbricata was studied in 102 patients on Goodenough Island, Papua New Guinea. Trichophyton concentricum was isolated from 98 skin samples. Seven different clinical patterns of infection were distinguished: concentric, lamellar, lichenified , plaque-like, annular, palmar/plantar, onychomycosis. Hypopigmentation was a prominent feature of the infection. The disease was most common in male children or adult women. Relapse after therapy, including oral griseofulvin, in patients remaining in the area was the rule. There was no evidence to suggest that those affected were abnormally susceptible to skin infections. An ineffective immune response to the infection may well explain the high relapse rate after treatment and the extensive nature of the lesions. Other susceptibility factors, such as a genetic predisposition, may also be involved and account for the high prevalence of the infection in this area.

Immune responses of patients with tinea imbricata.

Tinea imbricata is a chronic dermatophyte infection caused by Trichophyton concentricum affecting large areas of the skin surface. Spontaneous improvement is unusual and relapse after apparently successful treatment is common. In this study in Papua New Guinea it was found that a high proportion of infected patients had immediate-type hypersensitivity (52%) or negative responses (46%) to intradermal trichophytin. The majority of patients failed to develop delayed-type hypersensitivity on skin testing or as assessed in vitro by leucocyte migration inhibition. However, 78% of patients investigated had antibody to T. concentricum. The relevance of T-lymphocyte hyporeactivity to persistence of the infection is discussed.