Case report: Sulfasalazine-induced hypersensitivity

Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a systemic inflammatory condition that is characterized by multisystemic involvement (liver, blood, and skin), heterogeneous manifestations (fever, rash, lymphadenopathy, and eosinophilia), and an unpredictable course; cases of DiHS/DRESS caused by sulfasalazine are rare in children compared to adults. We report a case of a 12-year-old girl with juvenile idiopathic arthritis (JIA) and sulfasalazine-related hypersensitivity who developed fever, rash, blood abnormalities, and hepatitis complicated with hypocoagulation. The treatment with intravenous and then oral glucocorticosteroids was effective. We also reviewed 15 cases (67% male patients) of childhood-onset sulfasalazine-related DiHS/DRESS from the MEDLINE/PubMed and Scopus online databases. All reviewed cases had a fever, lymphadenopathy, and liver involvement. Eosinophilia was reported in 60% of patients. All patients were treated with systemic corticosteroids, and one patient required emergency liver transplantation. Two patients (13%) died. A total of 40.0% of patients satisfied RegiSCAR definite criteria, 53.3% were probable, and 80.0% satisfied Bocquet's criteria. Only 13.3% satisfied typical and 20.0% atypical DIHS criteria from the Japanese group. Pediatric rheumatologists should be aware of DiHS/DRESS due to its similarities to other systemic inflammatory syndromes (especially systemic JIA, macrophage activation syndrome, and secondary hemophagocytic lymphohistiocytosis). Further studies of DiHS/DRESS syndrome in children are needed to improve its recognition and differential diagnostic and therapeutic options

Localized high-intensity light structures during multiple filamentation of Ti:sapphire-laser femtosecond pulses along an air path

The results of experimental studies of the transverse structure of a laser beam after multiple filamentation are presented. A ring structure of radiation is formed around individual filaments in a beam cross section inside the multiple filamentation domain, and at a dozen meters from it a common ring structure starts forming surrounding postfilamentation light channels (PFC). It is shown that the spectra of the PFC, rings, and beam are significantly different. The ring spectrum broadens asymmetrically relative to the carrier wavelength and is mainly concentrated in the short wavelength region. The PFC spectrum has a significant and more symmetrical broadening and covers the range 630–1000 nm

Filamentation of collimated Ti:sapphire-laser pulses in water

The results of experimental studies of the spatial characteristics of multiple filamentation terawatt femtosecond Ti:Salaser in water are presented. With an increase in initial power laser pulses increases the number of filaments, the length of the field is increased filamentation and reducing the length of the filaments have been shown. The distribution of the filaments in the longitudinal direction of the field of multiple filamentation has a maximum cross-sectional filament is shifted from the center to the periphery of the beam at the end region of filamentation. The minimum diameter of the beam on the track corresponds to the position of the maximum number of filaments. After the point of maximum impulse essentially loses energy in the initial direction of propagation. Upon reaching the pulse power 2 104 Pcr of multiple filamentation area is formed of a hollow cone, the apex directed to the radiation source

Multiple filamentation Ti:Sapphire-laser pulses in water

The results of experimental studies of the spatial characteristics of multiple filamentation terawatt femtosecond Ti:Salaser in water are presented. With an increase in initial power laser pulses increases the number of filaments, the length of the field is increased filamentation and reducing the length of the filaments have been shown. The distribution of the filaments in the longitudinal direction of the field of multiple filamentation has a maximum cross-sectional filament is shifted from the center to the periphery of the beam at the end region of filamentation. The minimum diameter of the beam on the track corresponds to the position of the maximum number of filaments. After the point of maximum impulse essentially loses energy in the initial direction of propagation. Upon reaching the pulse power 2 104 Pcr of multiple filamentation area is formed of a hollow cone, the apex directed to the radiation source

Multiple filamentation of laser pulses in the glass

Results are presented of experiments on investigation of the spatial characteristics of multi-filamentation region of giga- and terawatt pulses of a Ti:sapphire laser in a glass. Dependences are obtained of the coordinate of the beginning of filamentation region, number of filaments, their distribution along the laser beam axis, and length of filaments on the pulse power. It is shown that with increasing radiation power, the number of filaments in the multi-filamentation region decreases, whereas the filament diameter has a quasiconstant value for all powers realized in the experiments. It is shown that as a certain power of the laser pulse with Gauss energy density distribution is reached, the filamentation region acquires the shape of a hollow cone with apex directed toward the radiation source

Filamentation of focused and collimated laser beams in liquids

Experimental results of investigations into the transformation of the spectral and spatial characteristics of femtosecond collimated and focused Ti:Sapphire-laser beams with wavelengths of 800 and 400 nm upon filamentation in continuous liquid media are presented. It is shown that broadening of the laser pulse spectrum due to phase self-modulation in the medium with a cubic nonlinearity depends on the pulse power and beam diameter. Dependences of the number of filaments, width of laser radiation spectrum, nonlinear focusing distance, and diameter of the filamentation region on the laser pulse power are measured. The existence of a relative power interval in which the explosive growth of the number of filaments occurs, is established. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only

Filamentation of collimated Ti:sapphire-laser pulses in the glass

The results of experiments to study the spatial characteristics of multiple filamentation gigawatt laser pulses in the glass are presented. It is shown that with increasing pulse power multiple filamentation region increases in length and diameter, the distribution of filaments within the region has a maximum value when the power > 105 Pcr area filamentation takes the form of a hollow cone, the apex directed to the source of the laser radiation

Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2\u2009cm; P\u20091.5\u2009cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8\u2009cm vs 652.8\u2009cm (94% vs 85% by 10 years; P\u2009=\u20090.020; 80% vs 50% at 10 years; P\u2009=\u20090.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8\u2009cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs

Identification and rescue of a tRNA wobble inosine deficiency causing intellectual disability disorder

The deamination of adenosine to inosine at the wobble position of tRNA is an essential post-transcriptional RNA modification required for wobble decoding in bacteria and eukaryotes. In humans, the wobble inosine modification is catalyzed by the heterodimeric ADAT2/3 complex. Here, we describe novel pathogenic ADAT3 variants impairing adenosine deaminase activity through a distinct mechanism that can be corrected through expression of the heterodimeric ADAT2 subunit. The variants were identified in a family in which all three siblings exhibit intellectual disability linked to biallelic variants in the ADAT3 locus. The biallelic ADAT3 variants result in a missense variant converting alanine to valine at a conserved residue or the introduction of a premature stop codon in the deaminase domain. Fibroblast cells derived fromtwo ID-affected individuals exhibit a reduction in tRNA wobble inosine levels and severely diminished adenosine tRNA deaminase activity. Notably, the ADAT3 variants exhibit impaired interaction with the ADAT2 subunit and alterations in ADAT2-dependent nuclear localization. Based upon these findings, we find that tRNA adenosine deaminase activity and wobble inosine modification can be rescued in patient cells by overexpression of the ADAT2 catalytic subunit. These results uncover a key role for the inactive ADAT3 deaminase domain in proper assembly with ADAT2 and demonstrate that ADAT2/3 nuclear import is required for maintaining proper levels of the wobble inosine modification in tRNA