Predicting outcome in severe heart failure. Who will benefit from device therapy (CRT)?

Dyssynchronous ventricular contraction in severe heart failurecontributes to low cardiac output, worsening symptoms, and poorprognosis. Recognition of the effect of dyssynchrony in heartfailure, and the possibility of manipulating the sequence ofelectrical cardiac activation to improve the efficiency of mechanicalevents, led Cazeau et al. to attempt four-chamber pacing in1994.¹ This early system could stimulate both atria and bothventricles extrinsically, and could dictate the temporal relationshipbetween atrial systole and ventricular systole, and the ventriculo-ventricularrelationship. Modern cardiac resynchronization therapy (CRT),involving pacing of the right and left ventricles, with rightatrial pacing to optimize atrio-ventricular delay, has evolvedrapidly from this beginning. Left bundle branch block (LBBB) on the surface electrocardiogram(ECG) has been considered a marker of mechanical dyssynchronyas it represents a delay in conduction of depolarization tothe left ventricle, with the greatest delay usually being in     

Issues and challenges in staging of pressure ulcers.

Wound assessment is a key element of effective wound care, and assessment of pressure ulcers includes accurate determination of wound stage. Although the original staging system established by Shea was based on his understanding of the pathology involved in pressure ulcer development, subsequent staging systems (and the one currently in use) were intended simply to establish the level of tissue damage. Recently, clinicians have drawn attention to numerous limitations associated with the current staging system, including the inability to differentiate between an inflammatory response involving intact skin and a deep tissue injury (deep bruising) underneath intact skin. This is a clinically significant difference because clinicians have noted that most inflammatory responses resolve with intervention, whereas most areas of deep tissue injury progress to full-thickness ulcers even when appropriate intervention is provided. A second area of controversy involves partial-thickness (Stage 2) lesions; because many of these lesions are caused by maceration and/or friction (as opposed to pressure) clinicians are frequently unclear regarding which of these lesions should be staged. In response to these concerns, the National Pressure Ulcer Advisory Panel convened a consensus forum and published white papers to clearly outline the issues; they solicited clinician feedback on the white papers and the Wound, Ostomy, Continence Nurses Society provided a written response. This article summarizes the key points of the white papers, WOCN Society response, and consensus forum discussion.     

Fusidic acid viscous eyedrops – an evaluation of pharmacodynamics, pharmacokinetics and clinical use for UK optometrists

Recent changes in UK law have allowed UK-based optometrists to sell and supply fusidic acid viscous eyedrops, providing it is in the course of their professional activity and in an emergency. Alternatively, the optometrist may access fusidic acid viscous eyedrops, for a named patient, using a written order supplied to a pharmacy. This review provides details of the legal background to these changes, examines the common causes of a bacterial conjunctivitis, examines the mechanism of action of this narrow spectrum antibiotic as a bacteriostatic agent, reviews the susceptibility of common ocular isolates of bacteria to the drug and presents details of the expected pharmacokinetics of the viscous eyedrops. From this perspective, a systematic review is provided of the clinical studies which have investigated the use of fusidic acid viscous eyedrops and their outcome. The indicated use is generally for the treatment of bacterial conjunctivitis and/or blepharoconjunctivitis, especially that caused by Staphylococcus, but not Streptococcus or Haemophilus sp. (more likely associated with concurrent nasopharyngeal infections). The usual regimen for use is twice daily for 5-10 days, depending on severity, and can initially be used more intensively (four times per day). It may also be used for the management of corneal and conjunctival abrasions and foreign body injuries, or some cases of chronic blepharitis.     

Acute effects of ultraviolet-B irradiation on the corneal surface of the pigmented rabbit studied by quantitative scanning electron microscopy

The eyes of female pigmented rabbits were exposed to a single dose of UV-B (300 +/- 9 nm, 0.05 J/cm2 total dose) between 13.30 and 15.00 h. The average irradiance was 225 +/- 36 microW/cm2 delivered over 191 to 264 s. At various time periods thereafter (24, 48, 72 and 96 h post-irradiation), the animals were euthanized by pentobarbital overdose and the eyes fixed with 2% glutaraldehyde in 80 mM cacodylate buffer (pH 7.4, total osmolarity of 330-340 mOsm/L). Corneal quadrants were examined by high resolution scanning electron microscopy at 100 X and 500 X at-stage magnification at central, mid-peripheral and peripheral sites. The micrographs from the central cornea were subjected to a quantitative analysis using a computer based digitization system. A peak effect was observed at 48 h at which cellular exfoliation was noted at the corneal apex. In the region immediately adjacent to the exfoliating cells, the number of light and dark electron reflex cells decreased to 48 h while the numbers of medium-reflex cells decreased after 48 h. The relative surface area of all cells was also decreased at 48 h compared to unirradiated controls. Significant recovery was observed by 96 h. Mid-peripheral and peripheral sites were largely unaffected by this just supra-threshold irradiation.     

Eosinophil-enriched inflammatory response to schistosomula in the skin of mice immune to Schistosoma mansoni.

Exposure of the mouse skin to Schistosoma mansoni cercariae gives rise to acute, exudative inflammation in both normal and immune mice, but the immune response is anamnestically accelerated and is oesinophil-enriched, thereby enhancing opportunities for tegumental contact of schistosomula with host leukocytes, particularly with eosinophils. Many of the inflammatory changes occurring within the first 48 hours after exposure are due to cercarial products, e.g., "penetration tracts," but some remain demonstrable when schistosomula metamorphosed in vitro are injected intradermally and are therefore directed against the schistosomula themselves, such as the leukocyte "streaming patterns" seen in their pathways. In contrast to earlier observations in primates, cellular responses to schistosomula in the mouse lung 4 days after penetration are minimal in either normal or immune mice. Thus, immune cellular responses to schistosomula in mice are limited to an early time period after cercarial penetration and are morphologically suggestive of an antibody-mediated response rather than of delayed hypersensitivity. Our observations complement earlier evidence suggesting that antibody-mediated host leukocyte contact with schistosomula initiates the killing of challenge parasites in immune mice, with the eosinophil probably playing a crucial role.     

Immunolocalization of intercellular adhesion molecule-1 and leukocyte functional associated antigen-1 in schistosomal soluble egg antigen-induced granulomatous hyporesponsiveness

In this work, the changes in expression of the adhesion molecules ICAM-1/LFA-1 on inflammatory cells of the liver were studied by immunohistochemistry. Mice sensitized with SEA and infected with S. mansoni and S. mansoni-infected controls were examined from day 35 to day 56 postinfection. A significant upregulation of ICAM-1 and LFA-1 in both the SEA group and the infected control group started shortly after egg deposition at day 35 and persisted up to day 56 p.i. Notably, both ICAM-1 and LFA-1 expression peaks were shifted earlier to day 38 p.i. in the SEA group compared to day 40 in the infected control group. The distribution of ICAM-1 and LFA-1 in both groups was comparable. At the early phase of infection before granuloma formation, both ICAM-1 and LFA-1 were detected along the sinusoidal wall of small blood vessels. At the acute cellular granuloma phase, they were homogeneously distributed all over the inflammatory cells, while at the chronic fibrocellular stage a non-homogeneous staining of granuloma cells at the periphery of the granuloma was apparent. The present data suggest that adhesion molecules play a role in the initiation and maintenance of granuloma formation. Thus, the granulomatous hyporesponsiveness induced by sensitization with SEA was associated with reduced expression of adhesion molecules.