Tissue gene expression profiles and communication networks inform candidate blood biomarker identification in psoriasis and atopic dermatitis.

Overlapping clinical and pathomechanistic features can complicate the diagnosis and treatment of inflammatory skin diseases, including psoriasis and atopic dermatitis (AD). Spatial transcriptomics allows the identification of disease- and cell-specific molecular signatures that may advance biomarker development and future treatments. This study identified transcriptional signatures in keratinocytes and sub-basal CD4+ and CD8+ T lymphocytes from patients with psoriasis and AD. In silico prediction of ligand:receptor interactions delivered key signalling pathways (interferon, effector T cells, stroma cell and matrix biology, neuronal development, etc.). Targeted validation of selected transcripts, including CCL22, RELB, and JUND, in peripheral blood T cells suggests the chosen approach as a promising tool also in other inflammatory diseases. Psoriasis and AD are characterized by transcriptional dysregulation in T cells and keratinocytes that may be targeted therapeutically. Spatial transcriptomics is a valuable tool in the search for molecular signatures that can be used as biomarkers and/or therapeutic targets.

Daily Assessment of Stressful events and Coping in early post-operative recovery after colorectal cancer surgery.

This study describes the most stressful events and coping strategies used by patients with colorectal cancer 4-6 weeks after surgery and whether the coping strategies were considered helpful or not. For the investigation of situational coping, an exploratory design was used. One hundred and five patients from three Swedish hospitals were included to fill in the Daily Coping Assessment. Most stressful event, number and types of pre-defined coping strategies used, and if the coping strategy used was considered helpful or not, were measured for 5 days. Of 523 diary entries, 180 reported no stressful events. The most stressful event, also with worst level of control and expectation, was "Pain," followed by "Nausea/vomiting." The areas causing most stressful events were "Bowel-related" and "Surgery and treatment-related problems." Acceptance and Direct action were the most frequently used coping strategies. There was a wide range of perceived helpfulness if coping strategies were placed in relation to specific areas of events. The conclusion was that patients revealed several strategies for coping with stressful events but needed a higher level of preparedness for what might come and therefore need to be given appropriate support to cope during the early recovery phase. Such support is suggested to be person-centred and oriented towards individually adapting standardised regimens, given the variety of situations to which the stressful events reported in the study were related.

Staphylococcus aureus colonization related to severity of hand eczema.

Knowledge on Staphylococcus aureus colonization rates and epidemiology in hand eczema is limited. The aim of this study was to clarify some of these issues. Samples were collected by the "glove juice" method from the hands of 59 patients with chronic hand eczema and 24 healthy individuals. Swab samples were taken from anterior nares and throat from 43 of the 59 patients and all healthy individuals. S. aureus were spa typed and analysed by DNA-microarray-based genotyping. The extent of the eczema was evaluated by the hand eczema extent score (HEES). The colonization rate was higher on the hands of hand eczema patients (69 %) compared to healthy individuals (21 %, p < 0.001). This was also seen for bacterial density (p = 0.002). Patients with severe hand eczema (HEES ≥ 13) had a significantly higher S. aureus density on their hands compared to those with milder eczema (HEES = 1 to 12, p = 0.004). There was no difference between patients and healthy individuals regarding colonization rates in anterior nares or throat. spa typing and DNA-microarray-based genotyping indicated certain types more prone to colonize eczematous skin. Simultaneous colonization, in one individual, with S. aureus of different types, was identified in 60-85 % of the study subjects. The colonization rate and density indicate a need for effective treatment of eczema and may have an impact on infection control in healthcare.

High physical activity in young children suggests positive effects by altering autoantigen-induced immune activity.

Physical activity in children is associated with several positive health outcomes such as decreased cardiovascular risk factors, improved lung function, enhanced motor skill development, healthier body composition, and also improved defense against inflammatory diseases. We examined how high physical activity vs a sedentary lifestyle in young children influences the immune response with focus on autoimmunity. Peripheral blood mononuclear cells, collected from 55 5-year-old children with either high physical activity (n = 14), average physical activity (n = 27), or low physical activity (n = 14), from the All Babies In Southeast Sweden (ABIS) cohort, were stimulated with antigens (tetanus toxoid and beta-lactoglobulin) and autoantigens (GAD65 , insulin, HSP60, and IA-2). Immune markers (cytokines and chemokines), C-peptide and proinsulin were analyzed. Children with high physical activity showed decreased immune activity toward the autoantigens GAD65 (IL-5, P < 0.05), HSP60 and IA-2 (IL-10, P < 0.05) and also low spontaneous pro-inflammatory immune activity (IL-6, IL-13, IFN-γ, TNF-α, and CCL2 (P < 0.05)) compared with children with an average or low physical activity. High physical activity in young children seems to have positive effects on the immune system by altering autoantigen-induced immune activity.

Potential role of a navigator gene NAV3 in colorectal cancer.

BACKGROUND: The recently described navigator proteins have a multifaceted role in cytoskeletal dynamics. We report here on the relevance of one of them, navigator 3 (NAV3), in colorectal cancer (CRC). METHODS: We analysed changes in chromosome 12 and NAV3 copy number in CRC/adenoma samples of 59 patients and in 6 CRC cell lines, using fluorescence in situ hybridisation, loss of heterozygosity, and array-CGH. NAV3 target genes were identified by siRNA depletion, expression arrays, and immunohistochemistry. RESULTS: NAV3 deletion and chromosome 12 polysomy were detected in 30 and 70% of microsatellite stability (MSS) carcinomas, in 23 and 30% of adenomas and in four of six CRC cell lines. NAV3 amplification was found in 25% of MSS samples. NAV3 alterations correlated with lymph node metastasis. In normal colon cells, NAV3 silencing induced upregulation of interleukin 23 receptor (IL23R) and gonadotropin releasing hormone receptor. In MSS and microsatellite instability tumours, IL23R immunoreactivity correlated with Dukes' staging and lymph node metastases, whereas nuclear beta-catenin correlated with lymph node metastases only. CONCLUSION: NAV3 copy number changes are frequent in CRC and in adenomas, and upregulation of IL23R, following NAV3 silencing, strongly correlates with Dukes' staging and lymph node metastases. This suggests that NAV3 has a role in linking tissue inflammation to cancer development in the colon.

Stoma-related complications and stoma size - a 2-year follow up.

AIM: The purpose of the study was to prospectively describe stoma configuration and evaluate stoma-related complications and their association with possible risk factors. METHOD: All elective patients (n = 180) operated on with a formation of colostomy, ileostomy or loop-ileostomy between 2003 and 2005 were included in the study. Follow up took place on the ward postoperatively and five times during 2 years after discharge. On these occasions the diameter and height of the stoma were recorded. Complications such as peristomal skin problems, necrosis, leakage caused by a low stoma, stenosis, granuloma formation, prolapse and peristomal hernia formation were evaluated. RESULTS: Most complications occurred 2 weeks after discharge; 53% of patients with colostomies, 79% with loop-ileostomies and 70% of patients with end-ileostomy had one or more complications. The most common complication was skin problems and it was most common in patients with end-ileostomies (60%) and loop-ileostomies (73%). Postoperatively at ward review, the most common complication was necrosis, which occurred in 20% of patients with a colostomy. Granuloma formation was most frequent in colostomies. Almost all patients with an end-ileostomy and loop-ileostomy with a height lower than 20 mm had leakage and skin problems as had half of the patients with a colostomy height lower than 5 mm. CONCLUSION: To prevent stoma-related complications, it is important to produce an adequate height of the stoma, with early and regular follow ups and adjustment of the appliance. To work closely in collaboration with the colorectal surgeons is of utmost important to provide feedback and in turn, to improve stoma outcome.

Peste des petits ruminants (PPR) outbreak in Tajikistan.

The occurrence of outbreaks of peste des petits ruminants (PPR) in three districts of Tajikistan is described. The causal strain (PPR Tajikistan) was characterized and the sequence of its N gene was compared with that of 43 other strains isolated since 1968 in Africa, the Middle East and Asia. The study demonstrated (1) the value of the N gene as a target in comparing isolates obtained over an extended period of evolution, and (2) that clustering was related to the geographical origin of strains.

'Just so you know, the patient is staff': healthcare professionals' perceptions of caring for healthcare professional-patients.

OBJECTIVE: To explore healthcare professionals' conceptions of the care of patients who are also healthcare professionals. DESIGN: Explorative, with a qualitative, phenomenographic approach. PARTICIPANTS AND SETTING: 16 healthcare personnel within different professions (doctors, nurses, assistant nurses, physiotherapists, occupational therapists) were interviewed about the care of 32 patients who were themselves members of different healthcare professions, in one healthcare organisation in Sweden. RESULTS: The care of patients who are healthcare professionals was conceived in five different ways, as: usual, dutiful, prioritised and secure, insecure and responsive. An initial conception was that their care was usual, just as for any other patient, and also a perceived duty to treat them and to protect their right to be a patient--as any other patient. Exploring further, informants described that these patients did receive secure and prioritised care, as the informants experienced making a greater commitment, especially doctors giving privileges to doctor-patients. A conception of insecure care infused the informants' descriptions. This comprised of them feeling intimidated in their professional role, feeling affected by colleagues' stressful behaviour and ambiguity whether the healthcare professional-patient could be regarded as a competent professional. The deepest way of understanding care seemed to be responsive care, such as acknowledging and respecting the patient's identity and responding to their wishes of how treatment was to be met. CONCLUSIONS: Caring for healthcare professionals seems to trigger different ethical approaches, such as deontology and ethics of care. According to ethics of care, the findings may indeed suggest that these patients should be cared for just as any other patients would be, but only if this means that they are cared for as persons, that is, they are given 'person-centred care'. This would imply balancing between acknowledging the vulnerable patient in the colleague and acknowledging the identity of the colleague in the patient.

Development and validation of the preparedness for Colorectal Cancer Surgery Questionnaire: PCSQ-pre 24.

PURPOSE: The aims of the study were to develop and psychometrically evaluate a patient-reported outcome instrument for the measurement of preoperative preparedness in patients undergoing surgery for colorectal cancer. METHODS: This study was conducted in two stages: a) instrument development (item generation, construction of items and domains), empirical verification and b) instrument evaluation. A questionnaire with 28 items measuring preparedness for surgery was developed covering four domains and was tested for content validity with an expert panel and with patients. Psychometric testing of the questionnaire was conducted on 240 patients undergoing elective surgery for colorectal cancer. RESULTS: The scale content validity index of the preparedness items was 0.97. The final version consisted of 24 items measuring 4 subscales: Searching for and making use of information, Understanding and involvement in the care process, Making sense of the recovery process and Support and access to medical care. Confirmatory factor analysis revealed good model fit with standardized factor loadings ranging from 0.58 to 0.97. A well-fitting second-order factor model provided support for a total preparedness score with second-order factor loadings ranging from 0.75 to 0.93. The ordinal alpha values of the four latent factors ranged from 0.92 to 0.96, indicating good internal consistency. The polyserial correlations with the total score were 0.64 (p < 0.01) for the overall preparedness question and 0.37 (p < 0.01) for overall well-being. CONCLUSION: The Swedish Preparedness for Colorectal Cancer Surgery Questionnaire for use in the preoperative phase demonstrated good psychometric properties based on a sound conceptualization of preparedness.

Ventricular diastolic pressure-volume shifts during acute ischemic left ventricular failure in dogs.

Ischemic left ventricular failure was produced in eight acutely instrumented, anesthetized dogs to study the contribution of changing myocardial compliance and pericardial pressure to shifts in right and left ventricular diastolic pressure-volume relations. Right and left ventricular and pericardial volumes were measured by ungated computed tomography. Cardiac volumes were manipulated by infusion of saline solution, hemorrhage, phenylephrine infusion and, during failure only, nitroglycerin administration. During both control and failure periods, these interventions shifted the left and right ventricular pressure-volume relations by changing pericardial pressure only; that is, these interventions caused no change in the ventricular transmural pressure-volume relation. The induction of failure as such increased pericardial pressure only minimally and did not change the left ventricular or right ventricular transmural pressure-volume relations significantly. Volume loading during the control period caused an apparent pericardial creep which attenuated the pericardial effect on ventricular pressure-volume relations. During failure, volume loading caused an increase of right ventricular volume, but tended to decrease left ventricular volume; this was associated with a leftward displacement of the interventricular septum. In conclusion, in the presence of ischemic left ventricular failure as well as normally, changes in preload, afterload and circulating blood volume shift ventricular diastolic pressure-volume relations by stretching or relaxing the pericardium, thus changing pericardial pressure. In these circumstances, there were no consistent changes in myocardial compliance.

Ultrastructural localization of M-band proteins in chicken breast muscle as revealed by combined immunocytochemistry and ultramicrotomy.

Cryo-ultramicrotomy and "conventional" plastic sectioning have been used in combination with extraction and immunolabeling techniques to determine the location of the two M-band proteins characterized to date, MM-creatine kinase (MM-CK: Mr, 80,000) and M-protein "myomesin" (Mr, 165,000) within the M-region of chicken pectoralis muscle. The following main results were obtained. (1) The M-band in chicken pectoralis muscle contains five major striations (M1, M4 and M4', M6 and M6' in the terminology of Sjöström & Squire, 1977a). (2) Extraction of the bulk of the electron-dense M-band with low ionic strength removes the M-striations M1, M4 and M4' while M6 and M6' are retained. Cross-sections through the M-region of such muscles lack primary M-bridges connecting the thick myosin filaments. (3) Labeling with antibodies against MM-CK enhances the M-striations M4 and M4'; sometimes the whole region between M4 and M4' is labeled. (4) Incubation with antibodies against myomesin results in the labeling of the whole M-band from M6 to M6'; no label is found in the rest of the bare zone outside M6 and M6'. (5) Incubation of low ionic strength extracted muscle fibers with antibodies against myomesin leads to an "incomplete" labeling of the M-band between M6 and M6'; lines M6 and M6' are sometimes seen to be enhanced presumably due to antibody labeling. From these results it is concluded that MM-CK is the major protein of the M4 and M4' (and possibly also of the M1) M-bridges. Myomesin is bound within the M-band along the thick filaments from M6 to M6'. Two hypothetical models for the possible location of myomesin are discussed. According to these models myomesin would either make up the M-filaments or be directly attached to and along the central bare zone of thick myosin filaments.

Abnormal crossing of the optic fibres shown by evoked magnetic fields in patients with ocular albinism with a novel mutation in the OA1 gene.

AIM: To perform genealogical and clinical studies in Finnish families with X linked ocular albinism (OA1), including characterisation of the potential misrouting of optic fibres by evaluating visual evoked magnetic fields (VEFs), and to determine the mutation behind the disease. METHODS: Three families with OA1 were clinically examined. VEFs were measured in two affected males and in one female carrier to characterise the cortical activation pattern after monocular visual stimulation. The neuronal sources of the VEFs were modelled with equivalent current dipoles (ECDs) in a spherical head model. All coding exons of the OA1 gene were screened for mutations by single strand conformation analysis and direct polymerase chain reaction sequencing. RESULTS: Genealogical studies revealed that the three families were all related. The affected males had foveal hypoplasia with reduced visual acuity varying from 20/200 to 20/50, variable nystagmus, iris transillumination, and hypopigmentation of the retinal pigment epithelium. The ECD locations corresponding to the VEFs revealed abnormal crossing of the optic fibres in both affected males, but not in the carrier female. A novel point mutation, leading to a STOP codon, was identified in the fifth exon of the OA1 gene. CONCLUSIONS: The data indicate that the novel mutation 640C>T in the OA1 gene is the primary cause of the eye disease in the family studied. VEFs with ECD analysis was successfully used to demonstrate abnormal crossing of the optic fibres.

Differentiation of the myofibrils and the intermediate filament system during postnatal development of the rat heart.

The differentiation of the myofibrils and the intermediate filament system during postnatal development of the rat heart has been investigated. Several aspects of some of the structural proteins, that means the intermediate filament subunit skeletin, myosin, and the myofibrillar M-line proteins MM-creatine kinase and myomesin have been studied by using gel electrophoresis as well as enzyme and immunohistochemical techniques in combination with electron microscopy of both plastic and cryosectional material. We show that marked changes take place in the organization of the intermediate filament system and in the contractile apparatus, both in atria and in ventricles of the rat heart during postnatal development. In the newborn rats no dense myofibrillar M-bands were present in the M-region and the sarcomeric bands were irregular while in the four-week-old rats dense M-bands composed of a set of five crossbridges interconnecting the thick filaments were present. The sarcomeric bands were now regular. These observations are related to the presence of different isomyosins in the atria and in the ventricles of the newborn and the four-week-old rats, to the observation that MM-creatine kinase was only present in the M-region in the four-week old rats and to the physiological maturation of the heart.

Myocardial stress perfusion scintigraphy with rubidium-81 versus stress electrocardiography.

Fifty-six patients who subsequently underwent selective coronary angiography were studied noninvasively with relative myocardial perfusion scintigraphy with rubidium-81 and graded stress electrocardiography in an attempt to evaluate the ability of these tests to identify the presence of significant ischemia and, indirectly, coronary stenosis. Both the sensitivity (0.91) and specificity (0.91) of perfusion scintigraphy were impressive and better than the sensitivity (0.79) and specificity (0.64) of stress electrocardiography, the specificity of scintigraphy significantly so (P less than 0.05). Additionally, perfusion scintigraphy yielded excellent localizing information and was reliable even in the presence of drug effect, conduction abnormalities and nonspecific electrocardiographic abnormalities. Rare cases of triple vessel disease, prior myocardial infarction or single vessel disease with widespread collateral vessels were causes of scintigraphic misdiagnosis. Although ribidium-81 perfusion scintigraphy with the scintillation camera requires special collimation and significant quality control, it provides well resolved images and may prove particularly useful in facilitating quick successive multiple scintigraphic cardiac studies.

Some aspects of the pharmacology of beta-adrenorecptor blockers.

The pharmacodynamic properties of a beta-blocker are mainly determined by its affinity to beta1 and beta2-receptors respectively and by its intrinsic activity. It is suggested that there is no absolute organ separation of the two receptor sub-types. Instead both beta1 and beta2-receptors are involved in the mediation of the same effect. The frequency distribution ratio of beta1/beta2-receptors varied markedly among various effector responses. A non-selective and a beta1-selective blocker may have different haemodynamic effects when the levels of circulating adrenaline are high, because of their markedly different potency in inhibiting the beta2-mediated vasodilator effect of adrenaline. Data are presented which suggest the existence of a presynaptic beta1-receptor mediating a positive feedback mechanism on neuronal release of noradrenaline.

Review article: Esomeprazole--enhanced bio-availability, specificity for the proton pump and inhibition of acid secretion.

Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor available for clinical use as a single isomer. It demonstrates pharmacological and clinical benefits beyond those seen with the racemic omeprazole. Esomeprazole has higher and more consistent bio-availability than omeprazole, which results in a greater area under the plasma concentration-time curve. It is the area under the plasma concentration-time curve of omeprazole and esomeprazole that determines how much of each reaches the parietal cell, and thus the control of gastric acid secretion that is achieved. Esomeprazole, like other proton pump inhibitors, has a high specificity for the acidic environment of the parietal cell, where it is accumulated, activated and covalently inhibits the proton pump. Proton pumps elsewhere in the body do not achieve the level of acidity needed for accumulation and activation. Esomeprazole, 40 mg once daily, provides more effective control of gastric acid secretion than omeprazole, 20 or 40 mg once daily, and all other proton pump inhibitors given at their standard doses. This translates into greater clinical effect compared with omeprazole, 20 mg once daily, and lansoprazole, 30 mg once daily, in the management of reflux disease. Esomeprazole therapy is well tolerated, with a low adverse events profile, similar to that seen with omeprazole.

Noninvasive measurement of cardiac function during exercise, using resaturation curves.

The resaturation curve, a noninvasive indicator-dilution test using an ear oximeter to detect rates of change in arterial oxygen saturation during breathing of various concentrations of oxygen, was used to assess cardiac performance in normal subjects and in 108 patients with cardiac valvular disease. Measurements made during exercise included the time constant of resaturation (tau) and beat-to-beat changes in arterial oxygen saturation (the left heart clearance fraction). At maximum rates of voluntary work, patients had a significantly reduced clearance fraction and longer tau than normal subjects. Clearance fraction and tau improved in patients after aortic valve replacement; deterioration occurred in tau and clearance fraction over time in patients treated medically, as compared to normal subjects who showed little change during a ten-year period. Clearance fraction and tau correlated with hemodynamic data obtained during cardiac catheterization. The resaturation curve provides an objective measure of cardiac impairment that can be readily repeated during follow-up of patients with heart disease.

Repair of dissection of the thoracic aorta. Evaluation of false lumen utilizing computed tomography.

During the period 1975 to 1980, 21 patients with thoracic aortic dissections underwent surgical treatment. The operative technique was resection and tube graft replacement of the segment of the aorta containing the entry point into the false channel. Eleven Type A and 10 Type B dissections were resected. The hospital survival rate was 95%. The single operative death occurred in a patient with an acute Type A dissection. Three patients had total resection of the dissected segment; three had clotted false lumina; five had distal anastomosis to true and false lamina; and 10 had distal anastomosis to the true lumen only, with proximal entry into the false lumen obliterated by incorporating both intimal and adventitial walls in a single suture line. The late survival rate was 95% (mean 32 months, range 8 to 63 months). No late ruptures occurred. Computed tomography (CT) with contrast enhancement was used to evaluate the aorta and any residual false lumen at follow-up. Seven of eight patients in whom obliteration was attempted and CT scans performed demonstrated persistence of false lumen perfusion; in six of the eight, preoperative angiograms were adequate for evaluation of false lumen runoff. Major vessels arose from the false lumen in all cases, except in the one patient in whom obliteration was later successful. This report demonstrates that there is persistence of false lumen perfusion in patients in whom obliteration is attempted, and the mechanism of this persistence is the presence of major vessel runoff. It suggests that the mechanism by which long-term survival is achieved is by resection of the segment of aorta containing the entry site, which is frequently the site of subsequent enlargement and rupture, rather than obliteration of the false channel.

A method for the study of regional ischemic dysfunction in the intact dog. Permanent endocardial markers and the pressure-length loop.

A radiographic method for use in the closed-chest dog is described which allows the quantitation of segmental mechanical performance. Previous work has shown that the area of the pressure-length loop (an approximation of a stress-strain integral) is a useful measure of the mechanical work performed by a segment of myocardium. The position of radiopaque markers previously placed to define segments of myocardium is recorded by biplane cineradiography. From simultaneous measurements of left ventricular pressure the integral of pressure with respect to segment length during one cardiac cycle is calculated. An example illustrating the utility of this model for the study of regional myocardial ischemia is presented.

The effects of orientation on volume measurements of human left ventricular casts.

Biplane angiocardiography has emerged as a standard method for calculating left ventricular volume measurements. Validation of such measurements has separately been made for several projections of silicone casts of the left ventricle. This study was undertaken to establish and compare the regression lines for left ventricular cast volume measurements in the commonly used angiographic projections. Once established, any ventricular volume can be calculated from the slope and intercept of the regression line obtained from the appropriate angiographic projection.