Type 2N VWD: Conclusions from the Spanish PCM-EVW-ES project.

Introduction: Type 2N von Willebrand disease (VWD) is characterized by a decreased affinity of von Willebrand factor (VWF) for factor VIII (FVIII). Abnormal binding of FVIII to VWF (VWF:FVIIIB), results in low FVIII plasma levels, which can lead to a misdiagnosis of mild haemophilia A. Accurate diagnosis of type 2N VWD is essential for appropriate genetic counselling and therapy.

Unraveling the Influence of Common von Willebrand factor variants on von Willebrand Disease Phenotype: An Exploratory Study on the Molecular and Clinical Profile of von Willebrand Disease in Spain Cohort.

The clinical diagnosis of von Willebrand disease (VWD), particularly type 1, can be complex because several genetic and environmental factors affect von Willebrand factor (VWF) plasma levels. An estimated 60% of the phenotypic variation is attributable to hereditary factors, with the ABO blood group locus being the most influential. However, recent studies provide strong evidence that nonsynonymous single nucleotide variants (SNVs) contribute to VWF and factor VIII phenotypic variability in healthy individuals.

Unraveling the effect of silent, intronic and missense mutations on splicing: contribution of next generation sequencing in the study of mRNA.

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on mRNA. This study aimed to elucidate the true effects of 18 mutations on mRNA processing, investigate the contribution of next-generation sequencing to mRNA study in von Willebrand disease, and compare the findings with prediction.

Role of multimeric analysis of von Willebrand factor (VWF) in von Willebrand disease (VWD) diagnosis: Lessons from the PCM-EVW-ES Spanish project.

The multimeric analysis (MA) of plasma von Willebrand factor (VWF) evaluates structural integrity and helps in the diagnosis of von Willebrand disease (VWD). This assay is a matter of controversy, being considered by some investigators cumbersome and only slightly informative. The centralised study 'Molecular and Clinical Profile of von Willebrand Disease in Spain (PCM-EVW-ES)' has been carried out by including the phenotypic assessment and the genetic analysis by next generation sequencing (NGS) of the VWF gene (VWF).

Dermatitis Herpetiformis: A Review of Direct Immunofluorescence Findings.

Direct immunofluorescence (DIF) findings in dermatitis herpetiformis (DH) are incompletely defined. The presence and localization of immune reactants in this disorder are reviewed. A retrospective study on 72 biopsies from 71 patients with DH was performed.

Usefulness of specific anti-desmoglein 1 and 3 enzyme-linked immunoassay and indirect immunofluorescence in the evaluation of pemphigus activity.

Objective: The objective was to assess the relationship between enzyme-linked immunoassay (ELISA) values of desmoglein (Dsg) 1 and Dsg3 antibodies and indirect immunofluorescence (IIF) values of anti-epithelial antibodies with disease activity in patients with pemphigus.

Patients And Methods: In a retrospective study, we analyzed 353 serum samples taken from 35 patients with pemphigus vulgaris (PV) and nine with pemphigus foliaceus (PF) during the course of the disease. In each sample, we measured anti-Dsg1 and anti-Dsg3 antibodies by ELISA.

Determination of minimal erythema dose and anomalous reactions to UVA radiation by skin phototype.

Background: Phototesting is a technique that assesses the skin's sensitivity to UV radiation by determining the smallest dose of radiation capable of inducing erythema (minimal erythema dose [MED]) and anomalous responses to UV-A radiation. No phototesting protocol guidelines have been published to date.

Methodology: This was a multicenter prospective cohort study in which 232 healthy volunteers were recruited at 9 hospitals.

Acquired bullous dermatosis associated with IgA multiple myeloma: a case report.

We present the case of a patient with IgA paraprotein who developed hemorrhagic subepidermal vesicles and bullae with numerous neutrophils. Direct immunofluorescence test (DIF) showed weak deposits of IgA lambda paraprotein at the dermal-epidermal junction and at the intercellular level in the basal layer of the epidermis, and stronger deposits in a perivascular and diffuse pattern in the dermis. Indirect immunofluorescence (IIF) test revealed the presence of circulating IgA lambda antibodies reacting with the intercellular space of monkey and guinea pig esophagus and human skin.

Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence testing in a bullous pemphigoid and pemphigoid gestationis.

Enzyme-linked immunosorbent assay (ELISA) is an excellent tool for detection of circulating antibodies against the NC16A portion of BP180 antigen. We compared the sensitivity and specificity of a commercially available BP180-NC16a domain ELISA with that of an indirect immunofluorescence (IIF) testing in the evaluation of bullous pemphigoid (BP) and pemphigoid gestationis (PG), and analyzed the relationship between ELISA results and the presence of IgG deposition, in an epidermal or combined pattern, on direct immunofluorescence (DIF) testing of salt-split skin. ELISA was performed on serum from 28 patients (24 BP, 4 PG) and 50 controls.

Paraneoplastic pemphigus with negative direct immunofluorescence in epidermis or mucosa but positive findings in adnexal structures.

Introduction: Paraneoplastic pemphigus (PNP) is considered an autoimmune, multiorgan disease caused by antiplakin antibodies. We present three PNP patients who had negative epithelial direct immunofluorescence (DIF) findings in one or more biopsies.

Patients: An early lip biopsy of uninvolved oral epithelia in patient 1 was negative.

Evaluation of initial virological response to adefovir and development of adefovir-resistant mutations in patients with chronic hepatitis B.

The aims of the present study were to assess initial virological response (IVR) to adefovir (ADV) treatment for chronic hepatitis B, to identify patients with suboptimal response and to determine the incidence of ADV-resistant mutants. All patients treated with ADV for at least 12 months were evaluated for virological response and ADV resistance. IVR was defined as a reduction > or = 4 log10 IU/mL in hepatitis B virus (HBV)-DNA at month 6.

Therapy of paraneoplastic pemphigus with Rituximab: a case report and review of literature.

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease with poor prognosis when associated with malignant neoplasm. We report the case of a patient with PNP associated with a CD20+ non-Hodgkin follicular lymphoma who was treated with Rituximab plus corticosteroids and short courses of cyclosporin. One and a half years after Rituximab therapy, oral ulcerations had cleared and oral methylprednisolone was slowly tapered down without further recurrences.

High-performance liquid chromatography analysis of Bobel-24 in biological samples for pharmacokinetic, metabolic and tissue distribution studies.

A rapid and simple HPLC method is described for the determination of Bobel-24 (2,4,6-triiodophenol) and other iodinated derivatives in biological samples. The sample preparation was liquid-liquid extraction before injection onto the HPLC system. 2,6-Diiodo-4-methylphenol was used as internal standard.

Simple and robust high-performance liquid chromatographic method for the determination of ranitidine in microvolumes of human serum.

A simple robust high-performance liquid chromatographic method is described for the determination of ranitidine in microvolumes of human serum. The drug of interest was isolated using liquid-liquid extraction with dichloromethane and back-extraction with 0.1% phosphoric acid and separation was obtained using a reversed-phase column under isocratic conditions, with ultraviolet detection at 313 nm.

Determination of captopril in plasma by high-performance liquid chromatography for pharmacokinetic studies.

A high-performance liquid chromatographic method is described for the determination of free captopril in human plasma N-Acetyl-L-cysteine (NAC) was used as an internal standard. Plasma samples were immediately derivatized with N-(1-pyrenyl)maleimide (NPM) and stabilized with 11 M HCl. The drug of interest was isolated using a liquid-liquid extraction with ethyl acetate and separation was obtained using a reversed-phase column under isocratic conditions with fluorescence detection.

Diagnosis and staging of bronchogenic carcinoma by transtracheal and transbronchial needle aspiration.

Transbronchial needle aspiration (TBNA) has been used in diagnosis and staging of bronchogenic carcinoma. However, its true effectiveness seems uncertain and some models of needles are expensive. The aim of this study was to procure new experiences on this method.

Repeated exposure to ultraviolet A in polymorphous light eruption patients and normal subjects: a clinical and histopathological study.

The clinical and histopathological responses to repeated exposures of ultraviolet A were studied in patients with polymorphous light eruption and in normal controls. Variable degrees of perivascular and diffuse infiltrates (lymphocytic and neutrophilic) were detected in both groups. These findings indicate that more specific parameters should be used to distinguish reactive from pathological responses.

[In vitro stability of amikacin and ciprofloxacin administered through a Y-shaped catheter connection with 2 total parenteral nutrition formulations with different pH].

We studied the stability of amikacin and ciprofloxacin in in vitro coinfusion with two total parenteral nutrition. The antibiotic concentrations were determined by EMIT and HPLC for amikacin and ciprofloxacin, respectively. There were not significant differences between theoretical and measured concentrations.

Algorithms for dosage and therapeutic monitoring of theophylline.

Theophylline is widely prescribed in Spain. Because this drug has a narrow therapeutic range and high interindividual pharmacokinetic variability, it is essential to adapt the dosage to each patient. In order to simplify the drug individualization we are proposing three algorithms to apply to intravenous loading and maintenance doses and to oral doses.