Attentional bias for psoriasis-specific and psychosocial threat in patients with psoriasis

Information processing biases relate to the manner in which people attend to particular types of information more readily than others. This bias, which is central to cognitive models of disorder, has not been explored in patients with psoriasis. The purpose of this study was to examine whether patients with psoriasis show an automatic attentional bias to classes of information relative to controls. Sixty patients and 60 age- and sex-matched controls completed a computer-based attentional interference task (the modified Stroop task). Patients with psoriasis showed significant interference for disease-specific, self-referent, and others' behavior stimuli relative to controls. In terms of information processing biases, the relationship between subject status (psoriasis patient vs. control) and color-naming interference was significantly stronger than that between anxiety, depression and worry, and interference. Recall bias was limited to disease-specific stimuli only. The observed bias to threat is more appropriately accounted for by participant's status (i.e., psoriasis patient or control) than by psychological distress.     

MRI and fluorescence microscopy of the acute vascular response to VEGF165: vasodilation, hyper-permeability and lymphatic uptake, followed by rapid inactivation of the growth factor

Vascular endothelial growth factor (VEGF) is one of the key growth factors regulating tumor angiogenesis and thus it is one of the primary targets for antiangiogenic therapy. The long-term effects of VEGF include induction of proliferation and migration of endothelial cells, tube formation and maintenance of the immature capillaries. The early effects of VEGF include vasodilation and increased permeability. We hypothesize that the early responses to VEGF can serve to develop a quantitative measure of the activity of VEGF, and therefore may be applicable for monitoring the efficacy of systemic suppression of VEGF signaling during antiangiogenic therapy. For that end we tested the ability of MRI and fluorescence microscopy to detect the early response to intradermal VEGF165 in nude mice. VEGF-induced local vasodilation and increased permeability was detected by intravenous administration of macromolecular biotin-BSA-GdDTPA(23) 30 min after intradermal administration of VEGF. Contrast leak showed saturation kinetics. Delayed contrast administration (90 min after intradermal administration of VEGF) resulted in low contrast leak and demonstrated that the saturation kinetics is not due to contrast equilibration between plasma and the interstitial space, but rather is due to suppression of vascular permeability. Permeability was restored by a second bolus of VEGF, showing that the saturation kinetics is primarily due to inactivation of the growth factor. Confocal microscopy of fluorescent BSA-FITC confirmed the permeability changes monitored by MRI. Moreover, confocal microscopy showed efficient lymphatic uptake of the extravasated contrast material specifically in regions of VEGF induced hyper-permeability.     

Factors affecting the use of multifocal electroretinography to monitor function in a primate model of glaucoma

While elevated intraocular pressure (IOP) undoubtedly plays a crucial role in many glaucoma patients, vascular dysregulation and chronic regional ischemia are also thought to contribute to the pathophysiology of glaucoma. In an effort to critically evaluate hypotheses involving vascular abnormalities in glaucoma, Cioffi, Van Buskirk and co-workers have developed a model of optic neuropathy based on chronic regional ischemia. The multifocal electroretinogram (MERG) has previously been used to assess function in non-human primates with experimental glaucoma induced by high-IOP. In this study, the MERG was used to monitor function in macaque monkeys with experimental glaucoma induced by chronic anterior optic nerve ischemia. Initial recordings from experimental eyes, which were later documented histologically to have moderate axon loss, revealed little difference from recordings of control eyes. This suggested that many of the signal components in the macaque MERG, which are known (from other studies) to be eliminated by intravitreal injections of NMDA/TTX or by high-IOP experimental glaucoma, may also be affected by the choice of anesthetic agents and MERG recording parameters. Subsequent experiments were performed to specifically evaluate the effects of bipolar versus monopolar signal derivation, anesthetic agents, MERG stimulus design and spatial scale. The results demonstrate that successful measurement of inner retinal and optic nerve head MERG components, especially those which have been shown by other investigators to originate with ganglion cell spiking activity, will depend critically upon the choice of anesthetic agents and recording parameters. One of the most important parameters seems to be use of a monopolar signal derivation, with the contralateral cornea serving as the reference position.     

Multifocal electroretinogram delays reveal local retinal dysfunction in early diabetic retinopathy.

PURPOSE: To identify local retinal abnormalities in diabetic patients with and without retinopathy, by using the multifocal electroretinogram (M-ERG). METHODS: Electroretinograms were recorded at 103 discrete retinal locations in each eye of eight persons with nonproliferative diabetic retinopathy (NPDR) and eight diabetic persons without retinopathy, using VERIS (EDI, San Mateo, CA). The amplitude and implicit time of each local (first-order) retinal response were derived and compared with normal values obtained from 16 age-matched, nondiabetic subjects. Maps of local response amplitude and implicit time were compared with fundus photographs taken at the time of testing. RESULTS: In eyes with NPDR, the implicit times of responses from retinal sites manifesting clinical pathologic fundus lesions (e.g., microaneurysms and focal edema), were markedly delayed (e.g., up to 7 msec from normal). Responses from adjacent retinal sites that were more normal in clinical appearance were also delayed, but to a lesser extent (e.g., 2-5 msec). Smaller, yet significant local response delays were also found in eyes without retinopathy. By contrast, local response amplitudes bore no consistent relationship to fundus abnormalities in eyes with retinopathy, and amplitudes were typically normal in eyes without retinopathy. CONCLUSIONS: The M-ERG reveals local retinal dysfunction in diabetic eyes even before retinopathy. The magnitude of delay of local ERG implicit time reflects the degree of local clinical abnormality in eyes with retinopathy. Local response delays found in some eyes without retinopathy suggest that the M-ERG detects subclinical local retinal dysfunction in diabetes. Analysis of M-ERG implicit time, independent of amplitude, improves the sensitivity of detection of local retinal dysfunction in diabetes.     

Neonatal encephalopathy with a pungent body odour

A neonate had transient unexplained bleeding into the gut, severe encephalopathy, and an abnormal pungent body odour. An inherited metabolic defect was excluded. The malodour was due to methanethiol and hydrogen sulphide, identified in urine. These sulphur compounds may have contributed to encephalopathy. Colonic bacteria were the probable source.

     

T-cell epitopes recognized within the 65,000 MW hsp in patients with IgA nephropathy.

IgA nephropathy (IgAN) is the commonest cause of glomerulonephritis and clinical exacerbation of IgAN is frequently associated with mucosal infection. T-cell receptor gamma delta (TCR gamma delta+) cells are increased in both the circulation and in renal biopsies of patients with progressive IgAN. We examined the hypothesis that specific peptides within the 65,000 MW heat-shock protein (hsp) might stimulate TCR gamma delta cells and play a part in the immunopathogenesis of IgAN. We studied T-cell proliferative responses stimulated by overlapping peptides derived from the sequence of mycobacterial 65,000 MW hsp. Three T-cell epitopes have been identified (peptides 51-65, 71-85 and 281-295). The three peptides have a synergistic effect and they stimulate significantly higher proliferation of T cells in patients with IgAN than in disease or healthy controls. This response was inhibited by monoclonal antibodies (mAb) to TCR gamma delta+ and human leucocyte antigen (HLA) class I, but not by mAb to HLA class II. The involvement of TCR gamma delta+ cells was confirmed by up-regulation of the proportion of TCR gamma delta+ cells when stimulated with the three specific peptides. We suggest that IgAN might be associated with mucosal infection by a variety of micro-organisms and that peptides within the microbial hsp cross-react with the homologous human hsp which may stimulate TCR gamma delta+ cells and play a part in the pathogenesis of IgAN.     

Contractile activation and force generation in skinned rabbit muscle fibres: effects of hydrostatic pressure.

1. Effects of hydrostatic pressure (range 0.1-10 MPa) on the isometric tension of skinned (rabbit psoas) muscle fibres were examined at 12 degrees C and at different levels of Ca2+ activation (pCa range 4-7); the effects on both the steady tension and the tension transients induced by rapid pressure release (< 1 ms) are described. 2. The steady tension was depressed by increased pressure (approximately 1% MPa-1) at a high level of Ca2+ activation (pCa approximately 4) whereas it was potentiated at lower Ca2+ levels (pCa > 6); the effects were reversible. 3. At maximal Ca2+ activation, the tension recovery following pressure release (10 MPa to atmospheric) consisted of a fast (approximately 30 s-1) and a slow (2-3 s-1) phase; the rate and the normalized amplitude (normalized to the steady tension at atmospheric pressure for a particular pCa) of the fast phase were invariant with changes in Ca2+ level. 4. The effects of changing Ca2+ level on the slow phase were complex; its positive amplitude at high Ca2+ levels changed to negative and the rate decreased to approximately 1 s-1 at low Ca2+ levels (pCa > 6.0). 5. Results are discussed in relation to previous studies on the effect of pressure on intact muscle fibres and the actin-myosin interaction. This work supports calcium regulation of cross-bridge recruitment rather than calcium regulation of the rate of a specific step in the cross-bridge cycle.     

Frequency,factors and costs associated with injection site infections: Findings from a national multi-site survey of injecting drug users in England

Background  

Injection site infections among injecting drug users (IDUs) have been associated with serious morbidity and health service costs in North America. This study explores the frequency, factors and costs associated with injection site infections among IDUs in England.     

Involving consumers in accreditation: the Irish experience.

BACKGROUND: Following the 2004 review of the Acute Care Accreditation Scheme, the Irish Health Services Accreditation Board (IHSAB) decided to increase the level of consumer involvement in the accreditation process by including consumers as members of the review teams assessing healthcare organizations. Such consumers were known as service user (SU) surveyors where SUs were defined as any person who has used the Irish health system, i.e. a patient or relative/carer, etc. OBJECTIVE: Consumer surveyors first participated in surveys in 2005 and a total of seven surveys took place that year. An evaluation of the role and participation of the consumer surveyor was conducted in 2006. METHODS: All stakeholder groups were consulted, i.e. consumer and peer review surveyors, applicant organizations and IHSAB staff, and a combination of qualitative and quantitative techniques was used. RESULTS: Stakeholders considered that consumer involvement introduced greater objectivity and credibility. Characteristics such as good communication and interpersonal skills, excellent powers of observation and objectivity were identified as important traits for consumer surveyors. There were some issues in relation to the clarity and consistency of their role in terms of the rating of criteria and their contribution to the accreditation report. There was support among the stakeholder groups for greater consumer involvement in the process by participating in additional tours and interviews. CONCLUSION: The evaluation highlights that the introduction of consumer surveyors has been successful but illustrates that their role and level of involvement in the process may need to be re-examined.     

Bilateral parotid enlargement as a presenting feature of bulimia nervosa in a post-adolescent male.

An unusual case of bulimia nervosa in a post-adolescent male is reported. The clinical presentation was one of painless parotid swelling of 3 years duration with marked weight loss and underlying metabolic alkalosis. The diagnostic significance of parotid salivary gland swellings is discussed.