Deroofing: A safe, effective and well-tolerated procedure in patients with hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a recurrent, debilitating, chronic disorder of the pilosebaceous unit. Although advances in HS treatment have been made, more than 45% of patients remain dissatisfied with systemic treatment, and more than one-third are dissatisfied with surgical procedures. OBJECTIVES: A prospective, observational study on the deroofing procedures in HS with special attention paid to patient satisfaction and complications. METHODS: HS lesions were assessed clinically and by the use of ultrasound. Patients reported outcomes, including pain, itch and satisfaction, were measured at 24 h post-surgery by a numeric rating scale (NRS) ranging from 0 to 10. Additionally, the timeline of objective wound closure reported by patients in (weeks), in addition to the need for any analgesics use, were both evaluated. RESULTS: The mean closure time of the post-deroofing wound was assessed as 4.4 ± 1.9 weeks. A statistically longer time was necessary for complete closure in males than in females (4.9 ± 2.2 weeks and 3.9 ± 1.6 weeks, respectively; p = 0.046). The closure time correlated positively yet weakly with the HS tunnel's width (r = 0.27, p = 0.016) and length (r = 0.228, p = 0.044). Patients assessed mean pain at 24 h post-op as mild with 0.7 ± 1.2 points according to NRS, with no differences between sexes. Similarly, itch in the first 24 h was assessed as mild with 1.8 ± 1.1 points, without differences between sexes. No pain, itch or adverse events were reported after 1 week following deroofing. Moreover, no cases of wound infection were reported. An overall patient satisfaction was assessed as 9.9 ± 0.4 points (range 9-10 points). CONCLUSION: Deroofing is an easy, effective and safe dermatosurgical procedure that does not require surgical experience or operating theatre. It is associated with no complications and very low post-op pain and should be part of holistic HS management.

Standard clinical computed tomography fails to precisely visualise presence, course and branching points of deep cerebral perforators.

BACKGROUND: Standard computed tomography (CT) images have earned a well-established position in neuroimaging. Despite that, CT is somehow limited by its resolution, which does not enable to distinctively visualise structures smaller than 300 µm in diameter. Perforating arteries, most of which measure 100-400 µm in diameter, supply important subcortical structures (thalamus, basal ganglia, internal capsule). Consequently, pathologies affecting these vessels (e.g. lacunar strokes) can have a devastating clinical outcome. The aim of our study was to assess standard CT's ability to visualise perforators and compare it with microscopic and micro-CT pictures. MATERIALS AND METHODS: We have obtained 6 brainstem and 17 basal ganglia specimens. We infused them with barium sulphate contrast medium administered into either vertebral or internal cerebral artery. After that, the specimens were fixed in formalin and subsequently a series of CT, micro-CT and microscopic examinations were performed. RESULTS: The median number of visualised perforators in brainstem and basal ganglia specimens was 8 and 3, respectively for CT and 18 and 7 for micro-CT (p < 0.05). Standard CT failed to clearly visualise branching points and vessels smaller than 0.25-0.5 mm (1-2 voxels) in diameter. Parallel vessels, like lenticulostriate arteries could not be differentiated in standard CT due to their proximity being smaller that the resolution. CONCLUSIONS: Basing on our results, we infer that CT is a poor modality for imaging of the perforators, presenting both quantitative and qualitative flaws in contrast with micro-CT.

Menisco-fibular ligament - an overview: cadaveric dissection, clinical and magnetic resonance imaging diagnosis, arthroscopic visualisation and treatment.

BACKGROUND: Injury to the menisco-fibular ligament (MFiL) is not commonly recognised. The anatomy of the lateral meniscus is complex and structure-function relationships are only partly understood. The purpose of the present study was to evaluate the MFiL, an anatomic structure rarely discussed that stabilises the lateral meniscus at the level of the hiatus popliteus and may have a crucial role in pathology of lateral meniscus injury. MATERIALS AND METHODS: The MFiL was dissected from its attachment at the lateral meniscus to its insertion on fibular head in 12 human normal cadaver knees. The dimensions were determined and its anatomic position visualised throughout a 90° range of motion. Findings were documented on digital photographs and on video. Results were compared against the magnetic resonance imaging (MRI) appearance of the injured MFiL in 20 patients. Concomitant knee injuries in those patients were also analysed to determine the most frequent pattern of injuries. RESULTS: The normal MFiL showed an inverted trapezoid-shape with a mean width proximally of 13 mm, mean width distally of 8.5 mm and a mean length of 18.4 mm. MRI visualisation of the ligament was possible even in regular sequences; however, additional radial plane sequences were also used. Arthroscopic visualisation and manipulation was optimal when the camera was inserted into the postero-lateral gutter with full knee extension. CONCLUSIONS: The MFiL stabilises the postero-lateral knee in concert with the menisco-femoral ligaments. Injury to the MFiL can be a cause of chronic postero-lateral pain syndrome with associated instability. Further anatomical and biomechanical studies are needed in order to fully evaluate its importance.

Opioid receptors expression in the skin of haemodialysis patients suffering from uraemic pruritus.

BACKGROUND: Uraemic pruritus is a common symptom in patients with chronic kidney disease undergoing haemodialysis (HD) treatment. Etiopathogenesis of uraemic pruritus is complex and not fully explained, but there are reports indicating a possible role of peripheral opioid system in its pathomechanism. OBJECTIVES: This study was undertaken to analyse the expression of mu- and kappa-opioid receptors in the skin of HD patients with and without uraemic pruritus. METHODS: Forty patients suffering from chronic kidney disease, treated with haemodialysis (21 pruritic and 19 non-pruritic), were included. The expression of mu- and kappa-opioid receptors in their skin was evaluated with immunohistochemistry. RESULTS: The significant (P < 0.02) decrease in kappa-opioid receptor expression was shown in the skin of pruritic patients in comparison with the skin of those without itch (1.07 ± 0.62 and 1.66 ± 0.85, respectively). Moreover, there was a significant negative correlation between intensity of pruritus and expression of kappa-opioid receptors (r = -0.63, P = 0.002). There was no difference in the expression of mu-opioid receptor expression in the skin of pruritic and non-pruritic HD patients. CONCLUSIONS: This study indicates that changes in peripheral opioid system may play an important role in the uraemic itch pathogenesis and that future studies are necessary to fully understand this mechanism.

Human skull translucency: post mortem studies.

Measurements of optical translucency of human skulls were carried out. An incandescent light source and a CCD camera were used to measure the distribution of light transmitted through the skull in 10 subjects post-mortem. We noticed that intra-individual differences in optical translucency may be up to 100 times but inter-individual translucency differences across the skull reach 105 times. Based on the measurement results, a "theoretical" experiment was simulated. Monte-Carlo calculations were used in order to evaluate the influence of the differences in optical translucency of the skull on results of NIRS measurements. In these calculations a functional stimulation was done, in which the oxyhemoglobin and deoxyhemoglobin concentrations in the brain cortex change by 5µM and -5µM respectively. The maximal discrepancies between assumed hemoglobin concentration changes and hemoglobin concentration changes estimated with Monte-Carlo simulation may reach 50% depending of the translucency of the skull.

Verification of the anatomy and newly discovered histology of the G-spot complex.

OBJECTIVES: To expand the anatomical investigations of the G-spot and to assess the G-spot's characteristic histological and immunohistochemical features. DESIGN: An observational study. SETTING: International multicentre. POPULATION: Eight consecutive fresh human female cadavers. METHODS: Anterior vaginal wall dissections were executed and G-spot microdissections were performed. All specimens were stained with haematoxylin and eosin (H&E). The tissues of two women were selected at random for immunohistochemical staining. MAIN OUTCOME MEASURES: The primary outcome measure was to document the anatomy of the G-spot. The secondary outcome measures were to identify the histology of the G-spot and to determine whether histological samples stained with H&E are sufficient to identify the G-spot. RESULTS: The anatomical existence of the G-spot was identified in all women and was in a diagonal plane. In seven (87.5%) and one (12.5%) of the women the G-spot complex was found on the left or right side, respectively. The G-spot was intimately fused with vessels, creating a complex. A large tangled vein-like vascular structure resembled an arteriovenous malformation and there were a few smaller feeding arteries. A band-like structure protruded from the tail of the G-spot. The size of the G-spot varied. Histologically, the G-spot was determined as a neurovascular complex structure. The neural component contained abundant peripheral nerve bundles and a nerve ganglion. The vascular component comprised large vein-like vessels and smaller feeding arteries. Circular and longitudinal muscles covered the G-complex. CONCLUSION: The anatomy of the G-spot complex was confirmed. The histology of the G-spot presents as neurovascular tissues with a nerve ganglion. H&E staining is sufficient for the identification of the G-spot complex.

rs3827440, a nonsynonymous single nucleotide polymorphism within GPR174 gene in X chromosome, is associated with Graves' disease in Polish Caucasian population.

Recently Chu et al. conducted a two-stage genome wide association study in Chinese that identified a novel X-linked Graves' disease (GD) susceptibility marker at rs3827440 - a nonsynonymous (P162S) nucleotide transition (519C

Experimental estimation of the photons visiting probability profiles in time-resolved diffuse reflectance measurement.

A time-gated intensified CCD camera was applied for time-resolved imaging of light penetrating in an optically turbid medium. Spatial distributions of light penetration probability in the plane perpendicular to the axes of the source and the detector were determined at different source positions. Furthermore, visiting probability profiles of diffuse reflectance measurement were obtained by the convolution of the light penetration distributions recorded at different source positions. Experiments were carried out on homogeneous phantoms, more realistic two-layered tissue phantoms based on the human skull filled with Intralipid-ink solution and on cadavers. It was noted that the photons visiting probability profiles depend strongly on the source-detector separation, the delay between the laser pulse and the photons collection window and the complex tissue composition of the human head.

The replication of the association of the rs6832151 within chromosomal band 4p14 with Graves' disease in a Polish Caucasian population.

Recently Chu et al. conducted a genome-wide association study in a Chinese Han population and identified two novel Graves' disease (GD) susceptibility loci within 4p14 (rs6832151) and 6q27 (rs9355610). Our purpose was to replicate these associations in a Polish Caucasian population. We analyzed rs6832151 and rs9355610 genotypes in a case-control study based on 560 GD patients and 1475 unrelated controls using TaqMan assays. Our study had the power of 0.8 and 0.6 to detect the effects originally reported for rs6832151 and rs9355610, respectively. We found an association between GD and the rs6832151 G allele (odds ratio OR = 1.27, P = 0.002). Analysis of model of inheritance suggested that the dominant model should be preferred (P(fit) = 0.938, OR = 1.39, P = 0.001). For rs9355610 a formally significant effect was observed assuming a recessive model (OR = 1.24, P = 0.028), whereas analysis of allele distribution showed a trend for association (OR = 1.14,95%, P = 0.082). Our findings are the first to show that rs6832151 and possibly rs9355610 contribute to GD pathogenesis also in Caucasians.

Differential association of juvenile and adult systemic lupus erythematosus with genetic variants of oestrogen receptors alpha and beta.

Oestrogens acting via nuclear receptors (encoded by ESR1 or ESR2) are important for pathogenesis of systemic lupus erythematosus (SLE). rs2234693 and rs4986938 are two single nucleotide polymorphisms (SNPs) whose C and A variants increase transcription of ESR1 and ESR2, respectively. The T allele of rs2234693 was associated with early onset SLE, whereas the role of rs4986938 in SLE was not reported. Our aim was to examine the role of rs2234693 and rs4986938 in conferring susceptibility to juvenile and adult SLE (jSLE and aSLE). Genotype distribution of both SNPs was analysed in 84 jSLE, 112 aSLE patients and 1001 controls. Allele C of rs2234693 was associated with jSLE (OR = 1.87, p = 0.006, p(corrected) = 0.02), whereas allele A of rs4986938 showed an association with aSLE (OR = 1.46, p = 0.008, p(corrected) = 0.03). In jSLE, rs2234693 C had lower frequency in patients with central nervous system involvement (OR = 0.39, p = 0.005, p(corrected) = 0.04) and showed a trend for increase among males, patients with renal involvement and those without DR2/3 (p < 0.05, p(corrected) > 0.05). Whereas our results are consistent with a role of ESR1 variation in jSLE, more studies are needed since the direction of association was the opposite of that reported previously. The association between rs4986938 (ESR2) and aSLE is a novel finding, consistent with our recent report associating this variant with Graves' disease.

Validation of 131I ecological transfer models and thyroid dose assessments using Chernobyl fallout data from the Plavsk district, Russia.

Within the project "Environmental Modelling for Radiation Safety" (EMRAS) organized by the IAEA in 2003 experimental data of (131)I measurements following the Chernobyl accident in the Plavsk district of Tula region, Russia were used to validate the calculations of some radioecological transfer models. Nine models participated in the inter-comparison. Levels of (137)Cs soil contamination in all the settlements and (131)I/(137)Cs isotopic ratios in the depositions in some locations were used as the main input information. 370 measurements of (131)I content in thyroid of townspeople and villagers, and 90 measurements of (131)I concentration in milk were used for validation of the model predictions. A remarkable improvement in models performance comparing with previous inter-comparison exercise was demonstrated. Predictions of the various models were within a factor of three relative to the observations, discrepancies between the estimates of average doses to thyroid produced by most participant not exceeded a factor of ten.

Validation of environmental transfer models and assessment of the effectiveness of countermeasures using data on (131)I releases from Chernobyl.

The studies undertaken by the (131)I Working Group, part of the International Atomic Energy Agency's EMRAS (Environmental Modelling for Radiation Safety) programme, were focused primarily on evaluating the predictive capability of environmental models. Particular emphasis was placed on applying models to evaluate the effectiveness of countermeasures.

Molecular background of polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome in a Polish population: novel AIRE mutations and an estimate of disease prevalence.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autosomal-recessive autoimmune disease caused by autoimmune regulator gene mutations. The aim of this study was to examine the mutation profile of Polish APECED patients, determine the carrier rate of the most frequent mutation(s) and estimate disease prevalence. While studying 14 unrelated patients, we identified three novel mutations (c.1A>T, affecting the start codon; [IVS1 + 1G>C; IVS1 + 5delG], a complex mutation affecting splice site; c. 908G>C, p.R303P, a missense mutation in plant homeodomain (PHD) and three previously reported mutations (c.769C>T, p.R257X; c.967_979del13bp, C322fsX372; c.931delT, p.C311fsX376). Eleven patients had mutations on both chromosomes, whereas in three patients only a single alteration with proven or likely pathogenic effect was detected. The most frequent was the p.R257X mutation (71% of chromosomes); its carriage rate was assessed in the background population. Analysis of 2008 samples showed eight heterozygotes, indicating the frequency of 0.40% (1:250) and the disease prevalence - 1:129,000 (95% confidence interval: 1:555,000 to 1:30,000). Comparison with an epidemiological estimate (1:619,000, derived for women) suggested that in Poland, APECED is underdiagnosed. Among the patients, no genotype/phenotype correlations were found, but we noted that women had earlier onset of hypoparathyroidism (p < 0.02) and were younger at diagnosis (p < 0.05) than men.

Model testing using data on 137Cs from Chernobyl fallout in the Iput River catchment area of Russia.

Data collected for 10 years following the Chernobyl accident in 1986 have provided a unique opportunity to test the reliability of computer models for contamination of terrestrial and aquatic environments. The Iput River scenario was used by the Dose Reconstruction Working Group of the BIOMASS (Biosphere Modelling and Assessment Methods) programme. The test area was one of the most highly contaminated areas in Russia following the accident, with an average contamination density of 137Cs of 800,000 Bq m-2 and localized contamination up to 1,500,000 Bq m-2, and a variety of countermeasures that were implemented in the test area had to be considered in the modelling exercise. Difficulties encountered during the exercise included averaging of data to account for uneven contamination of the test area, simulating the downward migration and changes in bioavailability of 137Cs in soil, and modelling the effectiveness of countermeasures. The accuracy of model predictions is dependent at least in part on the experience and judgment of the participant in interpretation of input information, selection of parameter values, and treatment of uncertainties.

Analyzing multi-environment variety trials using randomization-derived mixed models.

Of interest is the analysis of results of a series of experiments repeated at several environments with the same set of plant varieties. Suppose that the experiments, multi-environment variety trials, are all conducted in resolvable incomplete block (IB) designs. Following the randomization approach adopted in Calinski and Kageyama (2000, Lecture Notes in Statistics, 150), two models for analyzing such trial data can be considered. One is derived under a complete additivity assumption, the other takes into account possible different responses of the varieties to variable environmental conditions. The analysis under the first, the standard model, does not provide answers to questions related to the performance of the individual varieties at different environments. These can be considered when using the more general second model. The purpose of this article is to devise interesting parameter estimation and hypothesis testing procedures under that more realistic model. Its application is illustrated by a thorough analysis of a set of data from a winter wheat series of trials.

Model testing using data on 131I released from Hanford.

The Hanford test scenario described an accidental release of 131I to the environment from the Hanford Purex Chemical Separations Plant in September 1963. Based on monitoring data collected after the release, this scenario was used by the Dose Reconstruction Working Group of BIOMASS to test models typically used in dose reconstructions. The primary exposure pathway in terms of contribution to human doses was ingestion of contaminated milk and vegetables. Predicted mean doses to the thyroid of reference individuals from ingestion of 131I ranged from 0.0001 to 0.8 mSv. For one location, predicted doses to the thyroids of two children with high milk consumption ranged from 0.006 to 2 mSv. The predicted deposition at any given location varied among participants by a factor of 5-80. The exercise provided an opportunity for comparison of assessment methods and conceptual approaches, testing model predictions against measurements, and identifying the most important contributors to uncertainty in the assessment result. Key factors affecting predictions included the approach to handling incomplete data, interpretation of input information, selection of parameter values, adjustment of models for site-specific conditions, and treatment of uncertainties.

Relationship between CMV infection and coronary heart disease.

Conflicting evidence implicating CMV infection in coronary heart disease (CHD) exists. In this work using serological methods (IgM-CMV by Western blot and IgG-CMV by ELISA) correlation between CMV infection and CHD was not found. On the other hand presence of CMV DNA in atherosclerotic plaques with absence in unchanged vessel indicates possible role of CMV infection in progression of this process.

A nicked duplex decamer DNA with a PEG(6) tether.

A dumbbell double-stranded DNA decamer tethered with a hexaethylene glycol linker moiety (DDSDPEG), with a nick in the centre of one strand, has been synthesised. The standard NMR methods, E.COSY, TOCSY, NOESY and HMQC, were used to measure (1)H, (31)P and T:(1) spectral parameters. Molecular modelling using rMD-simulated annealing was used to compute the structure. Scalar couplings and dipolar contacts show that the molecule adopts a right-handed B-DNA helix in 38 mM phosphate buffer at pH 7. Its high melting temperature confirms the good base stacking and stability of the duplex. This is partly attributed to the presence of the PEG(6) linker at both ends of the duplex that restricts the dynamics of the stem pentamers and thus stabilises the oligonucleotide. The inspection of the global parameters shows that the linker does not distort the B-DNA geometry. The computed structure suggests that the presence of the nick is not disturbing the overall tertiary structure, base pair geometry or duplex base pairing to a substantial extent. The nick has, however, a noticeable impact on the local geometry at the nick site, indicated clearly by NMR analysis and reflected in the conformational parameters of the computed structure. The (1)H spectra also show much sharper resonances in the presence of K(+) indicating that conformational heterogeneity of DDSDPEG is reduced in the presence of potassium as compared to sodium or caesium ions. At the same time the (1)H resonances have longer T:(1) times. This parameter is suggested as a sensitive gauge of stabilisation.