New embedding and staining systems PrestoCHILL and Presto stainer for application in the advancement of Mohs micrographic surgery.

BACKGROUND: Mohs micrographic surgery (MMS) involves evaluation of frozen tissue sections to determine complete circumferential and deep tissue margin clearance of skin tumours. PrestoCHILL and Presto stainer devices are two new innovative tools which bring benefits of automation, speed and efficiency to the preparation of frozen section analysis in MMS. The devices were assessed at Viapath's Tissue Science Mohs laboratory at Guy's Cancer Centre. MATERIAL AND METHODS: A total of 279 samples from 10 anatomically different facial sites. These included nose (95), lip (24), forehead (47), cheek (25), eyelids (34), temple (9), chin (15), ear (17), scalp (6) and neck (7). These were analysed using both devices simultaneously. RESULTS: The PrestoCHILL device was measured for accuracy of tissue orientation by determining how many of the cases examined microscopically had complete margin and full epidermis preservation. The precision and reproducibility of the Presto stainer was evaluated by the consistency of achieving ideal standards of staining quality as defined by the department's internal quality control check, on stained sections examined and evaluated microscopically. The mean (standard deviation) score for accuracy for the PrestoCHILL across all tissue facial sites was 93.5 (11)%; the mean (standard deviation) score for precision/reproducibility of the Presto stainer was 96.5 (11)% (both p < 0.05). CONCLUSION: The devices combined offer an assured accuracy and precision performance, which is reproducible across all facial tissue types examined. The devices represent a key step forward in the introduction of improved automated embedding and staining procedures within MMS.

Expression and variability of lipid metabolism genes in intracranial aneurysm.

The objective of this study was to investigate the association between mRNA expression and single nucleotide polymorphisms (SNPs) of the ATP-binding cassette transporter (ABCA1) gene, apolipoprotein A1 (APOA1) gene, low-density lipoprotein (LDLR) gene and RNA gene located in the CDKN2B-CDKN2A cluster (CDKN2B-AS1) involved in lipid metabolism and the occurrence of intracranial aneurysm (IA). Fifty three IA patients, and 27 controls (IA-free) were enrolled in this study and were genotyped for seven single nucleotide polymorphisms. Increased expression of the LDLR gene in IA patients was observed. The A/G genotype and the A allele of the c. -113G>A polymorphism of the APOA1 gene were associated with increased occurrence of IA (ORs 12.36 and 14.14, respectively), while the G/G genotype and G allele showed the opposite tendency (ORs 0.06 and 0.07, respectively). We also detected that the A/A-G/A combined genotype of the c. -113G>A - APOA1 and g.46859A>G - LDLR SNPs was associated with a decreased occurrence of IA. Moreover, the A/G-G/G combined genotype of the c.656G>A - ABCA1 and c. -113G>A - APOA1 was associated with a decreased occurrence of IA. The results of our study suggest the association between expression and variability of lipid metabolism genes and occurrence of IA.

Patterns of service utilisation within Australian hepatology clinics: high prevalence of advanced liver disease.

BACKGROUND: Liver diseases in Australia are estimated to affect 6 million people with a societal cost of $51 billion annually. Information about utilisation of specialist hepatology care is critical in informing policy makers about the requirements for delivery of hepatology-related healthcare. AIMS: This study examined the aetiology and severity of liver disease seen in a tertiary hospital hepatology clinic, as well as the resource utilisation patterns. METHODS: A longitudinal cohort study included consecutive patients booked in hepatology outpatient clinics during a 3-month period. Subsequent outpatient appointments for these patients over the following 12 months were then recorded. RESULTS: During the initial 3-month period, 1471 appointments were scheduled with a hepatologist, 1136 of which were attended. Twenty-one per cent of patients were 'new cases'. Hepatitis B virus (HBV) was the most common disease aetiology for new cases (37%). Advanced disease at presentation varied between aetiology; only 5% of HBV cases had advanced liver disease at presentation, in contrast with HCV, NAFLD and ALD, in which advanced disease was identified at presentation in 31%, 46% and 72% of cases, respectively. Most patients (83%) attended multiple hepatology appointments, and a range of referral patterns for procedures, investigations and other specialty assessments were observed. CONCLUSIONS: There is a high prevalence of HBV in new case referrals. Patients with HCV infection, NAFLD and ALD have a high prevalence of advanced liver disease at referral, requiring ongoing surveillance for development of decompensated liver disease and liver cancer. These findings that describe the patterns of health service utilisation among patients with liver disease provide useful information for planning sustainable health service provision for this clinical population.

Induced sputum supernatant bioactive lipid mediators can identify subtypes of asthma.

BACKGROUND: Induced sputum (IS) allows to measure mediators of asthmatic inflammation in bronchial secretions. The specific role of induced sputum supernatant (ISS) endogenous bioactive lipid mediators in subtypes of asthma is not well understood. OBJECTIVE: To investigate the interactions between airway inflammation and clinical phenotypes of asthma, we integrated induced sputum supernatant (ISS) eicosanoids and quantitative assessment of infiltrating cells into new subtypes with the means of latent class analysis (LCA). METHODS: One hundred and thirty-nine asthmatics with and without aspirin hypersensitivity underwent sputum induction. High-performance liquid chromatography or gas chromatography coupled with mass spectrometry was used to profile eicosanoids. Nineteen variables covering clinical characteristics, IS inflammatory cells and eicosanoids were considered in the LCA. RESULTS: Four phenotypic asthma classes were distinguished. Class 1 with mild-to-moderate asthma, chronic rhinosinusitis (CRS), high PGA2 in ISS and almost equal distribution of inflammation cell patterns. Class 3 subjects also had mild-to-moderate asthma but without upper airway symptoms. Induced sputum was often paucigranulocytic with low levels of lipid mediators. Classes 2 and 4 represented severe asthma with CRS and impaired lung function despite high doses of steroids. High blood and sputum eosinophilia was in line with high cysteinyl leukotrienes and PGD2 in ISS only in class 2. Class 4 subjects tended to have increased sputum neutrophilia and PGE2 in ISS. Aspirin hypersensitivity was most frequent among class 2 subjects. CONCLUSIONS & CLINICAL RELEVANCE: The LCA revealed four distinct asthma classes differing in eicosanoid pathways.

Polymorphism of the LIG3 gene in keratoconus and Fuchs endothelial corneal dystrophy.

The product of the LIG3 gene encodes DNA ligase III, which is involved in the repair of oxidatively damaged DNA in the base excision repair pathway. We hypothesized that polymorphism in this gene may change susceptibility to oxidative stress and predispose individuals to the development of keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD). Therefore, we investigated the association between genotypes and haplotypes of the g.29661G>A polymorphism (rs1003918) and the g.29059C>T polymorphism (rs1052536) of the LIG3 gene and the occurrence of KC and FECD in patients with FECD (258 individuals) or KC (283) and ethnically matched controls (300). The A/A genotype and the A allele of the g.29661G>A polymorphism were associated with increased occurrence of KC, while the G allele of this polymorphism was positively correlated with a decreased occurrence of this disease. The T/C genotype of the g.29059C>T polymorphism was associated with decreased FECD occurrence. In addition, the AT haplotype was associated with increased occurrence of KC and FECD, while the GT haplotype was associated with decreased occurrence of these diseases. The g.29661G>A and g.29059C>T polymorphisms may play a role in the KC and FECD pathogenesis and can be considered as markers in these diseases.

Pan-cytokeratin markers for rapid frozen section immunocytochemistry from head and facial Mohs cases of basal cell carcinoma: a comparison and evaluation to determine the marker of choice.

The application of immunocytochemistry in the field of Mohs micrographic surgery (MMS) is well established. This study evaluates the use of pan-cytokeratins (AE1/AE3, MNF116 and AE1/AE3+PCK26) in the assessment of basal cell carcinoma (BCC) on frozen tissue debulk specimens. Fifty-five cases of BCC, all from head and facial sites, were assessed in the study. In addition to staining all cases for the three cytokeratin antibodies under investigation, sections were also stained with haematoxylin and eosin (H&E) to demonstrate tumour architecture and morphology. All sections for immunocytochemistry were stained on a Roche Ventana BenchMark Ultra automated platform employing a rapid frozen section protocol. Results were assessed based on the intensity of staining of keratinocytes (scale: 0-100%), as well as sensitivity of staining determined by the total percentage of keratinocytes stained within the tissue section. AE1/AE3 demonstrated the most consistent staining both in terms of intensity of staining and sensitivity, with a mean of 99.1% and 99.9%, respectively. AE1/AE3+PCK26 average results indicated scores of 70.6% for intensity and 87.2% for sensitivity, with MNF116 scoring 92.9% for intensity but only 57.3% for sensitivity. The data indicate that AE1/AE3 is the best pan-cytokeratin antibody to use in the assessment of BCC in MMS. The use of cytokeratin immunocytochemistry is justified in morphologically complex cases of BCC, or in cases where dense inflammatory infiltrate surrounding any suspicious cells make identification of small numbers of tumour cells difficult to determine with just an H&E stain. The significant rationale is that cytokeratin staining is a valuable adjunct in the study of tumour cell assessment in cases of MMS for BCC. In addition, the use of anti-AE1/AE3 cytokeratin antibodies provides the most consistent staining results for such cases.

Induced sputum eicosanoids during aspirin bronchial challenge of asthmatic patients with aspirin hypersensitivity.

BACKGROUND: Altered metabolism of eicosanoids is a characteristic finding in aspirin-exacerbated respiratory disease (AERD). Bronchial challenge with lysyl-aspirin can be used as a confirmatory diagnostic test for this clinical condition. Induced sputum allows to measure mediators of asthmatic inflammation in bronchial secretions. OBJECTIVES: To investigate the influence of inhaled lysyl-aspirin on sputum supernatant concentration of eicosanoids during the bronchial challenge test. Subjects with asthma hypersensitive to nonsteroidal anti-inflammatory drugs were compared with aspirin-tolerant asthmatic controls. METHODS: Induced sputum was collected before and following bronchial challenge with lysyl-aspirin. Sputum differential cell count and sputum supernatant concentrations of selected lipoxygenases products: 5-,12-,15-hydroxyeicosatetraenoic acid, cysteinyl leukotrienes, leukotriene B4 , 11-dehydro-thromboxane B2 , and prostaglandins E2 , D2 , and F2α and their metabolites, were measured using validated methods of chromatography-mass spectrometry. RESULTS: Aspirin precipitated bronchoconstriction in all AERD subjects, but in none of the aspirin-tolerant asthmatics. Phenotypes of asthma based on the sputum cytology did not differ between the groups. Baseline sputum eosinophilia correlated with a higher leukotriene D4 (LTD4 ) and leukotriene E4 (LTE4 ) concentrations. LTC4 , PGE2 , and 11-dehydro-TXB2 did not differ between the groups, but levels of LTD4 , LTE4 , and PGD2 were significantly higher in AERD group. Following the challenge, LTD4 and LTE4 increased, while PGE2 and LTB4 decreased in AERD subjects only. CONCLUSIONS: During the bronchial challenge, decrease in PGE2 and its metabolite is accompanied by a surge in bronchoconstrictory cysteinyl leukotrienes produced at the expense of LTB4 in AERD subjects. Bronchial PGE2 inhibition in AERD seems specific and sensitive to a low dose of aspirin.

Nonlocal correlations transmitted between quantum dots via short topological superconductor.

We study the quasiparticle states and nonlocal correlations of a hybrid structure, comprising two quantum dots interconnected through a short-length topological superconducting nanowire hosting overlaping Majorana modes. We show that the hybridization between different components of this setup gives rise to the emergence of molecular states, which are responsible for nonlocal correlations. We inspect the resulting energy structure, focusing on the inter-dependence between the quasiparticles of individual quantum dots. We predict the existence of nonlocal effects, which could be accessed and probed by crossed Andreev reflection spectroscopy. Our study would be relevant to a recent experimental realization of the minimal Kitaev model [T. Dvir et al., Nature 614, 445 (2023) ], by considering its hybrid structure with side-attached quantum dots.

Bradykinin mediated gastrointestinal edema as a cause of abdominal attacks in patients with hereditary angioedema due to C1-inhibitor deficiency.

Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency is a rare hereditary disease characterized by recurrent subcutaneous or submucosal angioedema due to uncontrolled bradykinin production caused by C1-INH dysfunction. Submucosal gastrointestinal swellings provoking abdominal attacks are common and mimic acute abdomen, thus constituting a diagnostic challenge. We aimed to investigate the difficulties in diagnosing abdominal attacks in patients with C1-INH-HAE and to assess the diagnostic value of medical history, the course of the attack, abdominal imaging, and treatment efficacy. The retrospective analysis of diagnostic problems and treatment complications of abdominal attacks in 274 patients with C1-INH-HAE were performed. The value of history, laboratory findings, prodromal symptoms and course of attacks and imaging were assessed. Abdominal attacks were confirmed in 274 of the 322 patients (85%; 190 women and 84 men; age, 4-70 years). In 49% of cases, the abdominal attack was the first and the only symptom for years. The simultaneous presence of marginal erythema (45% of cases), subcutaneous edema (30%), and pharyngo-laryngeal edema (10%) facilitated the diagnosis of an abdominal attack due to C1-INH-HAE. Abdominal attacks manifested with recurrent acute abdominal symptoms lasting 2 to 5 days. The disease course was characterized by the phase of progressive prodromal symptoms followed by peak symptoms and spontaneous symptom resolution. Abdominal imaging often revealed abundant ascites and limited bowel edema. In 60 cases (22%), the diagnostic difficulties resulted in exploratory laparotomy, which was inconclusive in 48 patients (80%). The attacks usually subsided within 2 hours from the administration of recommended drugs (plasma-derived C1-INH, recombinant C1-INH or icatibant). We conclude that recurrent abdominal attacks lasting a few days and resolving spontaneously were common symptoms of C1-INH-HAE. Abdominal imaging revealed transitional fluid or bowel edema. The effectiveness of recommended drugs as plasma-derived C1-INH, recombinant C1-INH or icatibant confirmed the diagnosis.

Validation of Diaporthe toxica resistance markers in European Lupinus angustifolius germplasm and identification of novel resistance donors for marker-assisted selection.

The fungus, Diaporthe toxica, anamorph Phomopsis sp., previously classified as P. leptostromiformis, is a plant endophyte and occasional pathogen, causing Phomopsis stem blight. This disease is damaging not only to lupins but also to the animals grazing on infected plants, due to the toxic secondary metabolites called phomopsins. The aim of this work was to validate markers for resistance to Phomopsis stem blight in narrow-leafed lupins and identify novel germplasm with increased levels of resistance to the disease. Plant inoculations were performed using ten isolates of D. toxica, originating from Australia and Poland. The European core collection of L. angustifolius was evaluated both in a controlled environment and with field experiments to classify the accessions based on their resistance to the disease. Simultaneously, the accessions were assayed with disease resistance markers to identify donors of hypothetical resistance alleles. We have found that the European lupin germplasm collection preserves wild and domesticated donors of at least two resistance genes to Phomopsis stem blight, including Phr1 and PhtjR. Molecular markers PhtjM7, InDel2, and InDel10, tagging PhtjR gene, were applicable for marker-assisted selection targeting the European gene pool with an expected accuracy of 95%. None of diagnostic markers for the Phr1 locus was found useful for European breeding programs; two existing markers Ph258M1 and Ph258M2 were unreliable, due to a high percentage of false-positive results (up to 58%) and a high recombination rate between markers (~ 30%).

Immunohistochemical detection of V600E BRAF mutation is a useful primary screening tool for malignant melanoma.

BACKGROUND: We compared the use of an immunohistochemical (IHC) method using a monoclonal antibody to BRAF V600E (which detects the main BRAF mutation) with existing DNA probe screening in tissue samples from 71 patients with malignant melanoma. MATERIALS AND METHODS: Paraffin blocks were cut to provide consecutive slides for haematoxylin and eosin staining, and for known positive micro-array DNA control material. IHC was performed by the Optiview detection system. All slides were scored independently by the clinical lead and the laboratory lead using a positive/negative system. RESULTS: The DNA method found 26 samples to be positive, the IHC found 21 to be positive, giving a sensitivity value for IHC of 80.8%. However, all of the 45 samples found to be negative by DNA were also negative by IHC, giving a specificity of 100%. There were 66 instances of full agreement, giving a concordance of 93%. Together, these data give a kappa statistic of 0.843, indicating very good agreement. CONCLUSION: The data reveal a very close link between the two methods, supporting the use of the V600E as a primary screen for BRAF mutations in malignant melanoma. Samples found to be negative by this method may be retested by the DNA probe method. IHC detection conserves patient DNA from tumour blocks as only one section is required to perform the assay. The V600E antibody method is considerably cheaper and faster than the DNA probe assay, with a turn-around time of 24-48 hours, enabling more rapid clinical management.

Exposure to air pollution and oxidative stress markers in patients with potentially malignant oral disorders.

The etiopathogenesis of potentially malignant oral disorders (PMOD) has not been fully understood yet. Recent results suggest that oxidative stress may be involved in the etiology of PMOD. Production of oxidants seems to be the major biological effect responsible for tissue injury and inflammatory response to air pollution. The aim of this study was to compare the oxidative stress markers and antioxidant potential in saliva of PMOD subjects and healthy controls in periods of high and low air pollution. Among enrolled 40 participants, there were 20 PMOD patients and 20 healthy volunteers. The exposure to air pollution was assessed by exhaled CO (eCO). Four oxidative status parameters: 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), reduced glutathione (GSH) and total antioxidant capacity (TAC) were measured in saliva. Measurements were carried out in June (low air pollution) and November (increased air pollution). In both groups, significantly higher concentrations of 8-OHdG (P < 0.001 for PMOD patients and P = 0.001 for healthy controls), MDA (P = 0.002 and P = 0.012 respectively) and eCO (P < 0.001 and P < 0.001 respectively) were observed in periods of high air pollution. The concentration of TAC did not change between visits. The concentration of salivary GSH (P < 0.001 and P < 0.001 for both groups) decreased when compared between consecutive visits. We conclude that exhaled carbon monoxide (reflecting exposure to air pollution) correlated with the oxidative stress markers in patients with PMOD and healthy controls.

Clinical characteristics of Polish patients with ANCA-associated vasculitides-retrospective analysis of POLVAS registry.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). METHODS: We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). RESULTS: Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3-12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06-9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05-6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3-25.5), skin involvement (OR = 4.4; 95% CI = 1.02-19.6), and age > 65 (OR = 6.3; 95% CI = 1.18-33.7). CONCLUSIONS: In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease.

Susceptibility testing and resistance phenotype detection in Staphylococcus aureus strains isolated from patients with atopic dermatitis, with apparent and recurrent skin colonization.

BACKGROUND: Staphylococcus aureus colonization is accepted to be an important triggering factor in patients with atopic dermatitis (AD) and antibiotic resistance has been recognized to be a serious problem as a consequence and for the management of AD treatment. OBJECTIVES: To investigate the antibiotic resistance pattern of S. aureus strains isolated from patients with AD with apparent (lesional and nonlesional skin areas) and recurrent skin colonization and strains obtained from healthy nasal carriers. METHODS: Eighty-seven patients (age 23+/-11.5 years) with mild to severe AD (SCORAD 46.9+/-16.6), 21 patients (age 19.8+/-6.7 years) before antistaphylococcal treatment and 177 healthy nasal carriers (age 27.5+/-8.4 years) were microbiologically assessed for carriage of S. aureus. Colonization of lesional and nonlesional skin areas was quantified by counting the number of colony forming units on the skin surface (log(10) CFU cm(-2)). Antimicrobial susceptibility and resistance phenotypes of 179 S. aureus strains were assessed with the agar disc-diffusion method. RESULTS: Staphylococcus aureus was isolated from 87% of lesional and 44% of nonlesional skin samples from patients with AD. The colonization density of S. aureus was markedly higher in lesional than in nonlesional skin (P<0.001), and was positively correlated with AD severity (P<0.001) and total serum IgE (P<0.05). Patients with AD had a significantly higher prevalence of chloramphenicol-resistant S. aureus than nasal carriers (P<0.01). Similar rates of resistance were expressed to tetracycline, erythromycin, mupirocin, clindamycin and penicillin. Nearly 35% of S. aureus strains from the lesional skin demonstrated different antimicrobial sensitivity pattern compared with strains from nonlesional skin of the same patients with AD. The trend of increasing resistance to chloramphenicol, erythromycin and fusidic acid was observed among S. aureus strains recovered from patients after approximately 75 days of antibiotic treatment. Methicillin-resistant S. aureus isolates were cultured from two patients, one during exacerbation and the other after subsequent bacterial recolonization. CONCLUSIONS: Discrepancies in antibiotic sensitivity pattern were observed among S. aureus strains colonizing different sites of AD skin (lesional and nonlesional areas), and also in AD patients with prior antibiotic treatment. Therefore, clinicians should consider repeat microbial susceptibility testing on different body sites of patients with AD when clinically indicated.

Erratum to "Nanocommunication via FRET With DyLight Dyes Using Multiple Donors and Acceptors".

In the above paper [1], an exponent is missing from equations (5) and (6). The correct version of the equations are as follows.

Strong spin Seebeck effect in Kondo T-shaped double quantum dots.

We investigate, taking a theoretical approach, the thermoelectric and spin thermoelectric properties of a T-shaped double quantum dot strongly coupled to two ferromagnetic leads, focusing on the transport regime in which the system exhibits the two-stage Kondo effect. We study the dependence of the (spin) Seebeck coefficient, the corresponding power factor and the figure of merit on temperature, leads' spin polarization and dot level position. We show that the thermal conductance fulfills a modified Wiedemann-Franz law, also in the regime of suppression of subsequent stages of the Kondo effect by the exchange field resulting from the presence of ferromagnets. Moreover, we demonstrate that the spin thermopower is enhanced at temperatures corresponding to the second stage of Kondo screening. Very interestingly, the spin-thermoelectric response of the system is found to be highly sensitive to the spin polarization of the leads. In some cases spin polarization of the order of 1% is sufficient for a strong spin Seebeck effect to occur. This is explained as a consequence of the interplay between the two-stage Kondo effect and the exchange field induced in the double quantum dot. Due to the possibility of tuning the exchange field by the choice of gate voltage, the spin thermopower may also be tuned to be maximal for desired spin polarization of the leads. All calculations are performed with the aid of the numerical renormalization group technique.

Conflicts and contradictions in current skin cancer screening guidelines.

PURPOSE OF REVIEW: To review skin cancer screening guidelines from major public health/medical organizations. RECENT FINDINGS: No consensus exists on whether or not screening to prevent skin cancer is warranted. SUMMARY: The best evidence of screening efficacy should come from population-based randomized trials, but is unlikely to exist due to feasibility constraints. Consequently, consensus should be built from observational/non-randomized designs, such as the SCREEN study in Germany. Current guidelines often focus on melanoma alone, while potential benefits of screening for non-melanoma skin cancers (NMSC) are largely overlooked. There may be less room for doubt regarding the value of screening, if both diseases were considered. Further, targeted approaches, i.e. screening only in high-risk populations, remain poorly defined and untested. Continuing to state that there is insufficient evidence to recommend screening leads to confusion about whether or not to screen, and is unlikely to result in substantial changes to the morbidity of NMSC and significant mortality from melanoma.

Coronary artery calcification, common carotid artery intima-media thickness and aortic pulse wave velocity in patients on peritoneal dialysis.

An increasing body of evidence suggests that atherosclerosis in patients with uremia differs from that found in general population in terms of advancement and localization of vascular lesions. It has also been suggested that different non-invasive techniques of vascular system evaluation are designed to show different types of lesions (i.e. vascular calcification, stiffness or 'classical' atherosclerosis). The aim of the study was to search for possible associations between results obtained with three different non-invasive methods of vascular system assessment in three different vascular sites in patients treated with peritoneal dialysis (PD). 61 patients (28 F, 33 M), mean age of 50.4+/-13.6 years, on maintenance PD for a median period of 10 months (range 1-96 months) were included. Coronary artery disease (CAD) was present in 21 subjects. In all subjects coronary artery calcification score (CaSc) using multi-row spiral computed tomography (MSCT), aortic pulse wave velocity (AoPWV) and ultrasound-based common carotid artery intima-media thickness (CCA-IMT) were performed as methods for assessing coronary calcium burden, arterial stiffness and atherosclerosis, respectively. Median value of CaSc equaled 11.5 Agatston units (range 0-5502.8 units). Median AoPWV was 10.4 m/s (range 7.56-18.1 m/s), and median CCA-IMT-0.6 mm (range 0.3-1.0 mm). In 16 patients (26.2%) at least one plaque in at least one common carotid artery was found on ultrasound. CaSc correlated with AoPWV (R=0.32, p<0.01) and with CCA-IMT (R=0.35, p<0.005), whereas no association was found between AoPWV and CCA-IMT. AoPWV, but not CaSc nor IMT correlated with blood pressure. The values of CCA-IMT and AoPWV increased together with consecutive Agatston categories (with p<0.001 for differences in AoPWV and p<0.05 for CCA-IMT). Patients with at least one plaque found in at least one CCA and patients with CAD were characterized with significantly higher values of CaSc, IMT and PWV, when compared to plaque-free and CAD- negative subjects, respectively. Association between CaSc and both IMT and PWV may suggest that the mechanism of three assessed vascular pathologies may be based, to some extent, on the process of pathologic calcium-phosphate deposition. Lack of correlation found between PWV and IMT may suggest that aortic stiffness and carotid atherosclerosis may partially differ in their pathologic background and/or are dissociated in time.

Facile and sensitive method for the determination of mesna in plasma by high-performance liquid chromatography with ultraviolet detection.

The use of 2-chloro-1-methylquinolinium tetrafluoroborate, an ultraviolet tagging reagent, for the ion-pair, reversed-phase high-performance liquid chromatography of mesna in human plasma is reported. In order to achieve this objective optimization of the two-step procedure, derivatization and separation of mesna S-quinolinium derivative from that of other thiols present in plasma and internal standard, was investigated. The derivatization was optimized in terms of pH, reagent excess and time of the reaction, and the mobile phase in terms of ion-pairing reagent concentration, pH, organic modifier content and temperature. Baseline separation was achieved on an analytical Waters Nova-Pak C18 (150x3.9 mm, 5 microm) column with a mobile phase consisting of pH 2.3 0.05 M trichloroacetic acid-acetonitrile (89:11, v/v) pumped at 1.2 ml/min. The peak height ratios of the mesna derivative to that of the internal standard (thiomalic acid) varied linearly with the concentration of the analyte added to normal plasma with a correlation coefficient of 0.9997. The lower limits of detection and quantitation were 40 pmol/ml (0.8 pmol on-column) and 160 pmol/ml (3.2 pmol on-column), respectively. The intra-run imprecision and inaccuracy were from 1.3 to 2.4 and from 1.3 to 2.0%, respectively.

An association between aortic pulse wave velocity, blood pressure and chronic inflammation in ESRD patients on peritoneal dialysis.

Increased aortic pulse wave velocity (AoPWV) has been identified as a risk factor for cardiovascular morbidity in the general population and in patients on dialysis. Most of the studies in ESRD patients refer to subjects on hemodialysis. Influence of the inflammatory process on aortic stiffening remains largely unknown. The aim of the present study was to evaluate potential relationships between AoPWV and blood pressure, basic anthropometric parameters, selected growth factors and markers of the inflammatory process in ESRD patients treated with peritoneal dialysis. The study population consisted of 43 patients (19 F, 24 M) with a mean age of 50.6 +/- 13.4 years on PD for a mean period of 21.9 +/- 20.7 months. AoPWV was measured using two pressure transducers placed on the carotid and femoral arteries and connected to an automatic processor (Complion Colson AS, Paris, France). Serum levels of Tumor Necrosis Factor alpha (TNFalpha), interleukin 6 (IL-6) and plasma basic Fibroblast Growth Factor (bFGF) were measured with ELISA; C-reactive protein and fibrinogen with nephelometry. Serum lipid profile was also assessed. Blood pressure was measured in an outpatient department under standardized conditions. Mean aortic pulse wave velocity in the study population was 10.7 +/- 2.1 m/s. No difference in AoPWV was found between men and women. AoPWV correlated significantly with age (R = 0.41; p < 0.01) but not with time on dialysis. Positive relationship between AoPWV and body weight and BMI was shown (R = 0.31; p < 0.05 and R = 0.35; p < 0.05, respectively). AoPWV correlated significantly with systolic blood pressure (SBP), mean arterial pressure (MAP) and pulse pressure (PP) (R = 0.46, p < 0.005, R = 0.46, p < 0.005 and R = 0.43, p < 0.01, respectively). AoPWV correlated with serum IL-6 and plasma bFGF (R = 0.32, p < 0.05 and R = 0.4, p < 0.01; respectively). The correlation with serum CRP was borderline significant (p < 0.53). In multiple regression analysis age (beta 0.38; p < 0.005), plasma bFGF level (beta 0.3; p < 0.05), and systolic blood pressure (beta 0.29; p < 0.05) were independently associated with pulse wave velocity. Our results suggest that AoPWV values in patients on PD are associated with factors similar to those encountered in the general population. We suggest that increased aortic stiffening may also be related to the chronic inflammatory process in PD patients.