Increased sensitivity and high specificity of indirect immunofluorescence in detecting IgG subclasses for diagnosis of bullous pemphigoid.

BACKGROUND: Indirect immunofluorescence (IIF) microscopy on monkey oesophagus is an important assay for the diagnosis of bullous pemphigoid (BP). Its relatively low sensitivity (60-80%) may be partly due to insufficient detection of minor IgG subclasses. AIM: To determine the operating characteristics of an IgG subclass in IIF. METHODS: We designed a retrospective, dual-centre, controlled cohort study on sera from 64 BP sera that had been rated as false negatives by traditional IIF microscopy, and assessed circulating IgG1 , IgG3 and IgG4 autoantibodies. RESULTS: The sensitivities of IIF in detecting IgG1 , IgG3 , IgG4 and all three in combination were 45.3%, 18.8%, 32.8% and 48.4%, respectively. Specificities were > 97%. CONCLUSION: Detection of IgG subclass (especially IgG1 and IgG4 ) autoantibodies by IIF on monkey oesophagus can significantly improve diagnostic performance of IIF microscopy for diagnosis of BP.

Meat allergy associated with galactosyl-α-(1,3)-galactose (α-Gal)-Closing diagnostic gaps by anti-α-Gal IgE immune profiling.

BACKGROUND: Glycoproteins and glycolipids of some mammalian species contain the disaccharide galactosyl-α-(1,3)-galactose (α-Gal). It is known that α-Gal is immunogenic in humans and causes glycan-specific IgG and also IgE responses with clinical relevance. α-Gal is part of the IgE-reactive monoclonal therapeutic antibody cetuximab (CTX) and is associated with delayed anaphylaxis to red meat. In this study, different α-Gal-containing analytes are examined in singleplex and multiplex assays to resolve individual sensitization patterns with IgE against α-Gal. METHODS: Three serum groups, α-Gal-associated meat allergy (MA) patients, idiopathic anaphylaxis (IA) patients with suspected MA, and non-meat-allergic healthy control individuals (HC), were analyzed via singleplex allergy diagnostics and a newly established immunoblot diagnostic system. The new dot blot detection system resolved individual IgE sensitization profiles for α-Gal-containing analytes CTX, bovine thyroglobulin (Bos d TG), and human serum albumin (HSA)-conjugated α-Gal. RESULTS: Singleplex allergy diagnostics using the α-Gal analytes CTX and Bos d TG confirms the history of MA patients in 91% and 88% of the cases, respectively. A novel dot blot-based assay system for the detection of IgE against α-Gal reveals individual IgE sensitization profiles for α-Gal-containing analytes. An α-Gal-associated IgE cross-reactivity profile (IgE against CTX, Bos d TG, and HSA-α-Gal) was identified, which is associated with MA. CONCLUSIONS: Detection of individual sensitization patterns with different α-Gal-containing analytes provides the basis for an individual allergy diagnosis for α-Gal-sensitized patients. Higher amounts of α-Gal in pork and beef innards compared to muscle meat as indicated by a higher staining intensity are a plausible explanation for the difference in allergic symptom severity.

Long-term outcome following treatment of Adamantinoma and Osteofibrous dysplasia of long bones.

INTRODUCTION: Adamantinoma (AD) is an ultimately rare, low-grade malignant bone tumor. In most cases it occurs in the tibia of young adults. Osteofibrous dysplasia (OFD) is a rare, benign, lesion that is typically seen in children. Histopathology, ultrastructure, and cytogenetics indicate that these lesions are closely related. Yet, etiology remains a matter of debate. Local recurrence rates are high for both entities as published in literature and long-term outcomes are scarce, due to the rarity of the disease. HYPOTHESIS: AD should be treated by En-Bloc resection while ODF can be treated by curettage or by observation. Consequently, the aim of the present study was to answer following questions: Were local recurrence rates of both entities different based on a retrospective review within a tertiary referral center for orthopedic oncology? MATERIAL AND METHODS: In a retrospective cohort study, 10 patients with AD and 5 patients with OFD (including 1 patient with OFD-like-AD) were reviewed. Primary surgeries for patients with AD were: En-bloc resection in 7, curettage in 2 and amputation in 1. In the OFD group, only 2 patients underwent surgery by curettage. Mean follow-up was 16 years (range: 2-47 years). Nine patients had a minimum follow-up of 10 years (mean: 23 years; range: 10-47 years). RESULTS: Four patients with AD (40%) and 2 patients with OFD (40%) - all of them following surgical removal - suffered from local recurrence. In the "En bloc" resection group of AD, there were 2 LR (29%). All patients of both groups treated with curettage showed LR. One patient with AD had metastasis at time of diagnosis and died of disease. Another patient with AD was diagnosed with metastasis 67 months after surgery and was still alive with disease at latest follow-up (77 month). DISCUSSION: The overall prognosis of AD and OFD is good, yet local recurrence rates are high, irrespective of surgical strategy. While an internationally standardized treatment regime is still missing, a more radical surgical approach should be considered, especially when treating AD. LEVEL OF EVIDENCE: Retrospective study; Level IV.

Domain wall dynamics in amorphous and nanocrystalline FeCoMoB microwires.

We have studied the domain wall dynamics in amorphous and nanocrystalline FeCoMoB microwires. The domain wall propagation velocity has been found very fast (up to 5000 m/s) for the as-cast sample. Annealing at 575 K/1 h leads to the stress relief and sample homogenization and the domain wall velocity even increases to 5300 m/s. However, the domain wall dynamics is highly sensible to the temperature of a measurement. Annealing at 775 K/1 h leads to the appearance of the nanocrystalline structure with much higher temperature stability. The maximum domain wall velocity decreases (2800 m/s), however the domain wall dynamics is much stable with the temperature.

Influence of the magnetoelastic anisotropy on the domain wall dynamics in bistable amorphous wires.

We deal with the influence of the applied stress on the domain wall velocity in glass-coated magnetic microwires. In general, the domain wall velocity decreases with the applied tensile stress. Four regimes of the domain wall dynamics appear: (1) diffusion-damped, (2) a regime with variable domain wall width, (3) a viscous and (4) a vortex regime. Detailed analysis of domain wall parameters shows that the structural relaxation plays an important role even at ambient temperatures if high tensile stress is present. At higher fields (viscous regime), the most important damping arises from magnetic relaxation of magnetic moments. Finally, the domain wall velocity steeply increases (reaching a maximum at 7000 m s(-1)) in the vortex regime and so does the domain wall mobility.

Synthesis and antimalarial activity of new amino analogues of amodiaquine.

Amodiaquine remains one of the most prescribed antimalarial 4-aminoquinoline. To assess the importance of the 4'-hydroxyl group and subsequent hydrogen bond in the antimalarial activity of amodiaquine (AQ), a series of new analogues in which this functionality was replaced by various amino groups was synthesized. The incorporation of a 3'-pyrrolidinamino group instead of the 3'-diethylamino function of AQ allowed the development of a parallel series of amopyroquine derivatives. The compounds were screened against both chloroquine (CQ)-sensitive and -resistant strains of Plasmodium falciparum and their cytotoxicity evaluated upon the MRC5 cell line. Antimalarial activity in a low nanomolar range was recorded showing that the 4'-hydroxy function can be successfully replaced by various amino substituents in terms of activity without any influence of the level of CQ-resistance of the strains. Furthermore the ability of the compounds to inhibit beta-hematin formation was measured in order to discuss the mechanism of action of these new compounds. Compounds 7d and 8d exhibit a high selectivity index and may be considered as promising leads for further development.

[Cavited pneumonia with Mycobacterium gastri positive culture smear]. / Neumonía cavitada con cultivo de esputo positivo para Mycobacterium gastri.

BACKGROUND: Mycobacterium gastri is an atypical non pigmented mycobacteria infrequent in clinical practice. Few reports have been published about infections caused by microorganism, and only three of them, all before 1986, were respiratory infections. METHODS: We report a case of cavitary pneumonia with sputum culture positive for Mycobacterium gastri, and we review the previous published cases. RESULTS: We describe a 79-years old man diagnosed of chronic obstructive pulmonary disease (COPD), with chronic respiratory failure, hypertension, Alzheimer's disease and multiple myeloma IgG lambda type IIA, with multiple previous admissions in our institution. He has again admitted because of an acute episode of cough and fever. The chest radiography demonstrated a right lower cavitary infiltrate, and the sputum culture showed growth of Mycobacterium gastri. DISCUSSION: We report a case of cavitary pneumonia in an immunocompromised patient caused by M. gastri resistant to isoniazid and pyrazinamide with fatal evolution. All of the cases previously described had a favourable outcome with the different treatment used.

Comparison of basophil activation tests using CD63 or CD203c expression in patients with insect venom allergy.

BACKGROUND: Flow cytometric basophil activation tests have been developed as cellular tests for in vitro diagnosis of IgE-mediated reactions. Different activation markers (CD63 or CD203c) with distinct ways of regulation have been used after stimulation with various allergens. OBJECTIVE: It was the aim of the present study to compare basophil activation tests by measuring both CD63 and CD203c upregulation in patients with insect venom allergy. MATERIALS AND METHODS: 43 patients with a history of insect venom anaphylaxis were examined. A careful allergy history was taken, and skin tests and determination of specific IgE-antibodies were performed. Basophil activation tests (BAT) using CD63 or CD203c expression were done after stimulation with different concentrations of bee and wasp venom extracts. 25 healthy subjects with negative history of insect venom allergy were studied as controls. RESULTS: The CD203c protocol showed a slightly higher sensitivity than the CD63 protocol (97% vs. 89%) with regard to patients' history. The magnitude of basophil response was higher with CD203c in comparison to CD63 for both insect venoms. Specificity was 100% for the CD63 protocol and 89% for the CD203c protocol with regard to controls with negative history and negative RAST. CONCLUSION: These results support the reliability of basophil activation tests using either CD63 or CD203c as cellular tests in the in vitro diagnosis of patients with bee or wasp venom allergy with a slightly higher sensitivity for the CD203c protocol.

OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele.

INTRODUCTION: The majority of hearing loss in children can be accounted for by genetic causes. Non-syndromic hearing loss accounts for 80% of genetic hearing loss in children, with mutations in DFNB1/GJB2 being by far the most common cause. Among the second tier genetic causes of hearing loss in children are mutations in the DFNB9/OTOF gene. METHODS: In total, 65 recessive non-syndromic hearing loss families were screened by genotyping for association with the DFNB9/OTOF gene. Families with genotypes consistent with linkage or uninformative for linkage to this gene region were further screened for mutations in the 48 known coding exons of otoferlin. RESULTS: Eight OTOF pathological variants were discovered in six families. Of these, Q829X was found in two families. We also noted 23 other coding variant, believed to have no pathology. A previously published missense allele I515T was found in the heterozygous state in an individual who was observed to be temperature sensitive for the auditory neuropathy phenotype. CONCLUSIONS: Mutations in OTOF cause both profound hearing loss and a type of hearing loss where otoacoustic emissions are spared called auditory neuropathy.

Single-domain wall propagation and damping mechanism during magnetic switching of bistable amorphous microwires.

The mechanism of nucleation and propagation of a single-domain wall is studied as a function of temperature in bistable Fe-based amorphous microwire with a unique simple domain structure. An extended nucleation-propagation model is proposed with a negative nucleation field. From quantitative analysis of the propagating wall characteristics, a new damping is theoretically introduced as arising from structural relaxation which dominates in the low temperature regime.

Biostereometric analysis for breast cancer detection.

A measurement technique has been developed for noninvasive breast cancer detection. The process involves the use of close-range stereophotogrammetry as a data acquisition device for the determination of breast surface concavities. We report the methodology used to detect these surface depressions, the rationale for the study, and our preliminary findings.

Validity and reliability of biostereometric measurement of the human female breast.

A measurement technique has been developed for application in the area of noninvasive breast cancer detection. The measurement process involves the use of close-range stereophotogrammetry as a data acquisition device necessary for determination of breast volume and volume distribution. This report details the methodology used to acquire and analyze stereopair photographs necessary to document the validity and reliability of this application. The volume of a test object was determined by both water displacement and stereophotogrammetric analysis to estimate the precision of the proposed methodology. Additionally, the reliability component of the study was documented by analyzing variability of coordinates representing a series of locations marked on the surface of an irregularly shaped object. Both tests confirm that this stereometric analysis is a reliable and valid method of measurement and may be well suited for further development in the field of breast cancer detection.

Breast cancer detection utilizing biostereometric analysis.

Twelve female patients participated in a study designed to employ computer-assisted biostereometric analysis for the detection of breast masses. All breast masses were previously documented by physical examination and followed by xeromammography, stereophotography, and histopathologic confirmation of tumor type. "Contour mammograms" were produced from the biostereometric photographs. These data were analyzed first for tumor detection and location by visual inspection. A second analysis employed a computed algorithm designed to locate and measure surface aberrations that suggest the possibility of underlying breast tumor. Visual analysis yielded the exact location of breast tumors in eight of the ten malignancies; computer analysis exactly located nine of the ten malignancies. In the computer analysis, one malignancy not exactly located by quadrant was, nevertheless, located in the correct breast. The results of the study suggest that the biostereometric process may have future use in screening or prescreening procedures for breast cancer detection. It is noninvasive, applicable to large numbers of women and with suitable refinements, and capable of being fully automated.