Imaging of Myocardial Fibrosis in Patients with End-Stage Renal Disease: Current Limitations and Future Possibilities.

Cardiovascular disease in patients with end-stage renal disease (ESRD) is driven by a different set of processes than in the general population. These processes lead to pathological changes in cardiac structure and function that include the development of left ventricular hypertrophy and left ventricular dilatation and the development of myocardial fibrosis. Reduction in left ventricular hypertrophy has been the established goal of many interventional trials in patients with chronic kidney disease, but a recent systematic review has questioned whether reduction of left ventricular hypertrophy improves cardiovascular mortality as previously thought. The development of novel imaging biomarkers that link to cardiovascular outcomes and that are specific to the disease processes in ESRD is therefore required. Postmortem studies of patients with ESRD on hemodialysis have shown that the extent of myocardial fibrosis is strongly linked to cardiovascular death and accurate imaging of myocardial fibrosis would be an attractive target as an imaging biomarker. In this article we will discuss the current imaging methods available to measure myocardial fibrosis in patients with ESRD, the reliability of the techniques, specific challenges and important limitations in patients with ESRD, and how to further develop the techniques we have so they are sufficiently robust for use in future clinical trials.

Outcome of elective withdrawal of anti-tumour necrosis factor-α therapy in patients with Crohn's disease in established remission.

BACKGROUND AND AIMS: Outcomes of cessation of anti-TNF therapy for Crohn's disease (CD) in clinical and/or endoscopic remission in routine clinical practice is uncertain. This study aimed to evaluate clinical outcomes and factors associated with relapse in CD patients following formal disease assessment and elective anti-TNF withdrawal. METHODS: Prospective observational study of CD patients in whom anti-TNF therapy was stopped electively after ≥12months and follow-up of ≥6months. Investigations at assessment prior to cessation included ≥1 of clinical assessment, endoscopic and/or imaging. Relapse was defined as recurrent symptoms of CD requiring medical or surgical therapy. RESULTS: Eighty-six patients received anti-TNF for a median duration of 23 (12-80) months for severe active luminal (70%), fistulating perianal (25.5%) and other fistulating disease (4.5%). Relapse rates at 90,180 and 365days were 4.7%, 18.6% and 36%, respectively. If anti-TNF dose escalation occurred 6months prior to withdrawal, 88% (7/8) relapsed. Based on multivariate analysis, risk factors for relapse include ileocolonic disease at diagnosis and previous anti-TNF therapy. An elevated faecal calprotectin (FC) is likely to predict relapse (p=0.02), with a PPV of 66.7% at >50µg/g. Of 36 patients who relapsed, 31 were retreated with anti-TNF, with an overall recapture rate of 93%. CONCLUSION: Relapse rates at 1year following elective withdrawal of anti-TNF are 36%, with high retreatment response rate. Predictors of relapse include ileocolonic involvement, previous anti-TNF therapy and raised FC. Endoscopic/radiologic assessment prior to cessation of therapy does not appear to predict those at lower risk of relapse.

Are hip protectors correctly positioned in use?

There are many designs of hip protectors ranging from small elliptical shaped hard shell designs to large circular soft pads. They are held in position usually by being contained in a close fitting pocket on a garment that patients wear all the time they are at risk of sustaining a fracture of the hip if they fall onto the area of the greater trochanter (GT). It is important for the function of the hip protector that the pad element is positioned over the GT when the subject falls onto a surface such as the floor so as to provide the maximal protection by reducing the large forces transmitted to the femoral neck that lead to the fracture of the bone. In this study, anatomical measurements show where the GT is relevant to the centre of the hip protector, and position and movement studies have shown that generally the hard shell design of the hip protector lies posterior and proximal to the GT both for erect and flexed positions of the hip. The position of the GT relevant to the anterior superior iliac crest was established using ultrasound examinations on control and patients admitted with a fracture of the hip due to a fall. The diagonal surface distance for the three groups of test subjects was approximately 12 cm and a template was developed that could be used to locate the GT. A 'zone' of GT position and movement has been established relative to the anterior superior iliac crest, and designers of garments should ensure that this zone is within the area of protection provided by their hip protector pad design.

Regulation of dendritic cell recruitment into resting and inflamed airway epithelium: use of alternative chemokine receptors as a function of inducing stimulus.

Dendritic cells (DC) were purified by flow cytometry from rat tracheal mucosa; they exhibited the phenotypic characteristics of immature DC including high endocytic activity, low CD80/86 expression, and in vitro responsiveness to a broad range of CC chemokines. Daily treatment of adult rats with the selective CCR1 and CCR5 antagonist Met-RANTES reduced baseline numbers of tracheal intraepithelial DC by 50-60%, and pretreatment of animals with Met-RANTES before inhalation of aerosol containing heat-killed bacteria abolished the rapid DC influx into the epithelium that occurred in untreated controls, implicating CCR1 and CCR5 and their ligands in recruitment of immature DC precursors into resting airway tissues and during acute bacterial-induced inflammation. Comparable levels of DC recruitment were observed during airway mucosal Sendai virus infection and after aerosol challenge of sensitized animals with the soluble recall Ag OVA. However, Met-RANTES did not affect these latter responses, indicating the use of alternative chemokine receptors/ligands for DC recruitment, or possibly attraction of different DC subsets, depending on the nature of the eliciting stimulus.

Rapid mass spectrometric analysis for ascorbate and related organic acids in small volumes of plasma for use in pediatric subjects.

A gas chromatographic-mass spectrometric isotope dilution method was developed for analysis of ascorbate on 10 microl samples of plasma. This assay was reproducible (standard deviation of less than 4%) and gave values for plasma ascorbate content within 8% of our previously published gas chromatographic-mass spectrometric method. Non-specific sample preparation allowed other analytes to be determined on the same sample by adjusting data acquisition parameters and adding the appropriate internal standard. Analysis on 28 subjects fell within the expected range for plasma ascorbate 68+/-29 microm (11.9+/-5.0 microg/ml) and established a normal range for plasma threonate of 28.1+/-2.4 microm (3.8+/-0.4 microg/ml).

Inflammatory infiltration of the upper airway epithelium during Sendai virus infection: involvement of epithelial dendritic cells.

We undertook the present study to determine the nature of the cellular inflammatory response within the epithelial lining of the rat trachea during a Sendai virus infection. In particular, we aimed to investigate changes in the resident population of epithelial dendritic cells. Rats were infected with Sendai virus, and tracheal tissue was examined immunohistochemically at various times with a panel of cell-specific monoclonal antibodies. We found that Sendai virus infection was restricted to only the lumenal layer of epithelial cells and that virus nucleoprotein was present from days 2 to 5 postinfection. Starting around day 2 or 3, there was a large cellular influx consisting of macrophages, neutrophils, NK cells, and T cells; this coincided with expression of high levels of ICAM-1 on the basal (uninfected) layers of the epithelium. The T cells were mostly alphabeta T-cell receptor positive; however, a smaller influx of gammadelta T cells also took place. The number of resident dendritic cells increased markedly during infection, with numbers peaking around day 5 and remaining elevated 14 days later. The peak of the inflammatory response occurred on day 5 and declined thereafter, with the exception of dendritic cell and alphabeta T-cell numbers, which remained elevated. Starting around day 3, the tracheal epithelial cells expressed increasing levels of major histocompatibility complex class II antigen. This expression was maximal at day 5 and declined rapidly thereafter. In vitro culture of tracheal segments demonstrated that viral infection was not per se responsible for the upregulation of class II expression and that when cultured in the presence of gamma interferon, class II antigen was induced on epithelial cells.

Dendritic cells are recruited into the airway epithelium during the inflammatory response to a broad spectrum of stimuli.

A key rate-limiting step in the adaptive immune response at peripheral challenge sites is the transmission of antigen signals to T cells in regional lymph nodes. Recent evidence suggests that specialized dendritic cells (DC) fulfill this surveillance function in the resting state, but their relatively slow turnover in most peripheral tissues brings into question their effectiveness in signaling the arrival of highly pathogenic sources of antigen which require immediate mobilization of the full range of host defenses for maintenance of homeostasis. However, the present report demonstrates that recruitment of a wave of DC into the respiratory tract mucosa is a universal feature of the acute cellular response to local challenge with bacterial, viral, and soluble protein antigens. Consistent with this finding, we also demonstrate that freshly isolated respiratory mucosal DC respond in vitro to a variety of CC chemokines as well as complementary cleavage products and N-formyl-methionyl-leucine-phenylalanine. This suggests that rapid amplification of specific antigen surveillance at peripheral challenge sites is an integral feature of the innate immune response at mucosal surfaces, and serves as an "early warning system" to alert the adaptive immune system to incoming pathogens.

HIV risk behaviour among injecting drug users in Perth: the Australian National AIDS and Injecting Drug Use Study.

OBJECTIVE: This study was carried out in 1989 to examine behaviour involving risk of human immunodeficiency virus (HIV) infection and to measure the prevalence of HIV antibodies in a sample of injecting drug users (IDUs) in Perth. DESIGN: The study was a cross-sectional survey with a sample of convenience of 196 IDUs drawn from drug treatment (54%) and non-treatment (46%) populations. RESULTS: Sixty-five per cent of the sample were men and 35% women. Subjects were predominantly heterosexual, were in their late twenties, had not completed secondary school, and were on sickness, unemployment or pension benefits. The majority were poly-drug users, but heroin and amphetamines were the only drugs that had been injected by more than 20% of the sample more than once a month. Respondents reported injecting an average of 43.6 (SD 83.6) times a month and using 33.7 (SD 55.4) new needles a month. The majority (70%) had injected within weeks of the interview. Sixty-seven per cent had shared needles within months. Respondents claimed to pass on used needles more frequently than to accept them, and were most likely to share with close friends or lovers when clean needles were unavailable and/or when they were withdrawing. While most respondents cleaned used needles, few used bleach all or most of the time. Most (78%) respondents had been tested for HIV seropositivity at least once. Most had multiple sexual partners and 92.3% had engaged in at least one unsafe sexual practice during the previous six months. Sixty-four per cent had changed some aspect of drug using, and 38% some aspect of sexual behaviour since hearing about the acquired immunodeficiency syndrome (AIDS). HIV seroprevalence for the 179 respondents who were tested was 2.2%, but this figure should not be taken as an estimate of seroprevalence for the Perth IDU population. CONCLUSION: Respondents' behaviour placed them at a high level of risk for HIV infection. Based on reported behaviour, it is recommended that education for IDUs in Perth should emphasise, among other things: not passing on used needles; cleaning used needles and syringes with bleach; planning ahead so that sterile equipment is available; and further risk reduction, particularly the adoption of safer sexual practices.

Airway obstruction associated with the use of the Guedel airway.

Soft tissue lateral neck radiography was used in 22 male patients older than 60 yr, to determine the cause of pharyngeal airway obstruction during anaesthesia, before and after insertion of a Guedel airway. In six of the patients, the airway was radiologically and clinically clear with the head in the neutral position. Nine patients showed obstruction of the airway by a "shelf" of tongue, but seven were cleared clinically by dorsiflexion at the atlanto-occipital joint, and the remaining two by the Esmarch-Heiberg manoeuvre. In four of the 22 patients, the Guedel airway was lodged in the vallecula in the neutral position. This was cleared clinically by dorsiflexion at the atlanto-occipital joint in all these patients. In three patients the Guedel airway was obstructed by the epiglottis, but this was cleared by dorsiflexion at the atlanto-occipital joint in two; in the third patient, the Guedel airway slipped into the vallecula after dorsiflexion at the atlanto-occipital joint and remained there despite the Esmarch-Heiberg manoeuvre. There was only one instance in 66 trials of a clinically obstructed airway without an apparent radiological cause. However, there were 10 instances in 66 trials of a clinically clear airway with an apparent radiological cause for obstruction.

Pneumothorax caused by minitracheotomy.

We describe a case in which misplacement of a minitracheotomy tube produced a pneumothorax, a complication which has not been reported previously. Methods to identify correct placement of the minitracheotomy tube are discussed.