EMPHYSEMATOUS PYELONEPHRITIS RESPONDING TO MEDICAL THERAPY

We describe two type 2 diabetic patients with unilateral emphysematous pyelonephritis who responded to medical treatment alone. Escherichia coli was isolated in both patients. The presence of gas was confirmed early by ultrasound and CT scan of abdomen. Following treatment, good functional recovery was demonstrable in the affected kidneys by isotope renogram. We stress the need for early diagnosis of this condition and aggressive treatment with broad spectrum antibiotics.     

Cystic fibrosis epithelial cells are primed for apoptosis as a result of increased Fas (CD95)

Background

Previous work suggests that apoptosis is dysfunctional in cystic fibrosis (CF) airways with conflicting results. We evaluated the relationship between dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) and apoptosis in CF airway epithelial cells.

FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo

Most Ig receptors exist as hetero-oligomeric complexes with separate ligand binding (alpha) and signal transducing (beta, gamma, or zeta) subunits. For Fc gamma RIIIa and Fc epsilon RI, association with the FcR gamma-chain is essential for surface expression. However, the human high affinity IgG receptor, hFc gamma RI, was found to be surface- expressed by itself in transient transfection models. We have now analyzed the integrity of hFc gamma RI expression in more detail in stable transfectants. In vitro we noted that, in the absence of FcR gamma-chain, surface expression of hFc gamma RI rapidly declined to background levels, in both IIA1.6 B cells and NIH3T3 fibroblasts. The effect of FcR gamma-chain on hFc gamma RI surface expression in vivo was evaluated by using two newly generated transgenic mouse lines, selectively expressing hFc gamma RI on myeloid cells. These transgenic mice were crossed with FcR gamma-chain-deficient mice. Analysis of blood monocytes and peritoneal macrophages showed that surface expression of hFc gamma RI was reduced by approximately 80%. The remaining approximately 20% of receptors were still capable of binding IgG-opsonized RBC, suggesting FcR gamma-chain not to be critical for hFc gamma RI ligand-binding capacity. Importantly, however, hFc gamma RI signaling capacity was lost in FcR gamma-chain-deficient cells. No phagocytosis could be observed using either ligand sensitized (EA- IgG2a) or CD64-targeted erythrocytes (using a bispecific antibody) in both hFc gamma RI transgenic lines. This documents the FcR gamma-chain to be indispensable for both surface membrane expression and function of human Fc gamma RI in vivo.     

Establishment of a system to standardize acceptability criteria for alanine aminotransferase activity in donated blood

A multilaboratory study was conducted to develop a system for standardizing alanine aminotransferase (ALT) acceptability criteria ("cutoffs") for donated blood. Without standardized cutoffs, each laboratory must develop its own cutoff, and this may not make optimal use of ALT testing to reduce transmission of non-A, non-B hepatitis (NANB). Defining an ALT acceptability criterion in absolute terms is necessary because relative cutoffs based on local donor populations may be affected by the prevalence of NANB in each community. This study involved 16 laboratories using 23 different analytic systems. The ALT results of the analysis of a plasma reference sample could be used to translate mathematically a single, absolute cutoff to units applicable to each analytic system. The distribution of ALT results in 1.4 million donations from across the country was established; basing the cutoff on this sample avoids the problems inherent in using a local donor base to establish a cutoff. We propose the implementation of a system to standardize ALT acceptability criteria to an activity level defined by analysis of a nationwide donor sample.     

Predictors of growth and body composition in HIV‐infected children beginning or changing antiretroviral therapy

Objectives

The aim of the study was to describe growth and body composition changes in HIV‐positive children after they had initiated or changed antiretroviral therapy (ART) and to correlate these with viral, immune and treatment parameters.

Methods

Ninety‐seven prepubertal HIV‐positive children were observed over 48 weeks upon beginning or changing ART. Anthropometry and bioelectrical impedance analysis results were compared with results from the National Health and Nutrition Examination Survey 1999–2002 (NHANES) to generate z‐scores and with results for HIV‐exposed, uninfected children from the Women and Infants Transmission Study (WITS). Multivariate analysis was used to evaluate associations between growth and body composition and disease parameters.

Results

All baseline lean and fat mass measures were below those of controls from NHANES. Weight, height and fat free mass (FFM) index (FFM/height²) z‐scores increased over time (P=0.004, 0.037 and 0.027, respectively) and the waist:height ratio z‐score decreased (P=0.045), but body mass index and per cent body fat z‐scores did not change. Measures did not increase more than in uninfected WITS controls. In multivariate analysis, baseline height, mid‐thigh circumference and FFM z‐scores related to CD4 percentage (P=0.029, P=0.008 and 0.020, respectively) and change in FFM and FFM index z‐scores to CD4 percentage increase (P=0.010 and 0.011, respectively). Compared with WITS controls, baseline differences in height and mid‐thigh muscle circumference were also associated with CD4 percentage. Case–control differences in change in both subscapular skinfold (SSF) thickness and the SSF:triceps skinfold ratio were inversely associated with viral suppression. No measures related to ART class(es) at baseline or over time.

Conclusions

In these HIV‐positive children, beginning or changing ART was associated with improved growth and lean body mass (LBM), as indicated by FFM index. Height and LBM related to CD4 percentage at baseline and over time. Altered fat distribution and greater central adiposity were associated with detectable virus but not ART class(es) received.     

Analysis of serious non‐AIDS events among HIV‐infected adults at Latin American sites

Objective

Acquired immune deficiency appears to be associated with serious non‐AIDS (SNA)‐defining conditions such as cardiovascular disease, liver and renal insufficiency and non‐AIDS‐related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Materials and methods

Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV‐associated factors on non‐AIDS‐defining conditions.

Results

Among 6007 patients in follow‐up, 130 had an SNA event (0.86 events/100 person‐years of follow‐up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non‐AIDS‐defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T‐cell count prior to index date (P=0.0056, with an average difference of more than 100 cells/μL) and area under the CD4 cell curve in the year previous to index date (P=0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors.

Conclusions

The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.     

A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines,KC/CXCL1 and LIX/CXCL5

Background and purpose:

Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.

Experimental approach:

Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.

Key results:

Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5.

Conclusion and implications:

Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.     

Does additional support by nurses enhance the effect of a brief smoking cessation intervention in people with moderate to severe chronic obstructive pulmonary disease? A randomised controlled trial

BACKGROUND: Smoking cessation is the primary disease modifying intervention for chronic obstructive pulmonary disease (COPD). SETTING: A Regional Respiratory Centre (RRC) out-patient department in Northern Ireland. METHODS: A randomised controlled trial (RCT) evaluated the effectiveness of brief advice alone or accompanied by individual nurse support or group support facilitated by nurses. Smoking status was biochemically validated and stage of change, nicotine addiction and dyspnoea were recorded at 2, 3, 6, 9 and 12 months. PARTICIPANTS: Ninety-one cigarette smokers with COPD were enrolled in the study (mean age 61 years, 47 female). RESULTS: After 12 months cessation rates were not significantly different between groups (p=0.7), but all groups had a significant reduction in their nicotine addiction (p=0.03-0.006). No changes in subjects' motivation or dyspnoea were detected over the 12 months. CONCLUSION: Patients with COPD were unable to stop smoking regardless of the type of support they received. Harm reduction may be a more appropriate goal than complete cessation for intractable smokers and nurses must evaluate their role in this arena.