Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are represented by rare but life-threatening cutaneous adverse reactions to different drugs. Previous studies have found that in a Han Chinese population from Taiwan and other Asian Countries, a strong genetic association between HLA-class I alleles (B*15:02, B*58:01) and SJS and TEN was induced by carbamazepine and allopurinol, respectively. To identify genetic markers that covered the MHC region, we carried out a case-control association enrolling 20 Caucasian patients with SJS/TEN. Our patient series included 10 cases related to paracetamol, 7 to allopurinol and 3 to different drugs (plaquenil, itraconazol, nabumetone). Healthy controls were represented by 115 Caucasian bone marrow or stem cell donors. The HLA-A*, B*, C*, DRB1*, DQB1*, DQA1* and DPB1* genotyping were determined. The frequencies of HLA-A*33:03 as well as C*03:02 and C*08:01 were significantly higher in SJS/TEN patient subgroup showing allopurinol drug-induced severe cutaneous adverse reactions (SCAR) as compared to controls (28.6% vs 0%, P=0.00002, Pc=0.0011; 28.6% vs 0%, P=0.00002, Pc=0.001; 28.6% vs 0%, P=0.00002, Pc=0.001, respectively). In the same subgroup the frequencies of B*58:01, DRB1*15:02 and DRB1*13:02 alleles, although considerably higher than in control group (42.8% vs 5.2%, P=0.003; 28.6% vs 1.7%, P=0.005; 28.6% vs 3.5%, P=0.037, respectively), appeared no more statistically different after P correction (Pc=0.248; Pc=0.29; Pc=1.00, respectively). In addition, in 10 of the 20 SJS/TEN patient subgroup with paracetamol-induced SCAR no statistically significant association with HLA alleles could be found. However, in the same SJS/TEN patient subgroup showing allopurinol drug-induced SCAR, haplotype analysis indicated that B*58:01, DRB1*13:02 and DRB1*15:02 alleles, that in a single allele analysis lost statistical significance after P correction, may still confer susceptibility, because the B*58:01-DRB1*13:02 and DRB1*15:02-DQB1*05:02 are positively associated with the disease (14.2% vs 0.43%, P= 0.00001, Pc=0.00028; 14.2% vs 0.43%, P=0.00001, Pc=0.00028, respectively). Our results show that in contrast to SCAR-related to paracetamol, where HLA alleles do not appear to be involved, HLA molecules behave as a strong risk factor for SCAR-related to allopurinol even when a limited number of patients are considered.
Rodent-borne hanta- and arenaviruses are an emerging public health threat in Europe; however, their circulation in human populations is usually underestimated since most infections are asymptomatic. Compared to other European countries, Italy is considered 'low risk' for these viruses, yet in the Province of Trento, two pathogenic hantaviruses (Puumala and Dobrava-Belgrade virus) and one arenavirus (Lymphocytic Choriomeningitis Virus) are known to circulate in rodent reservoirs. In this paper, we performed a follow-up serological screening in humans to detect variation in the prevalence of these three viruses compared to previous analyses carried out in 2002. We also used a statistical model to link seropositivity to risk factors such as occupational exposure, cutting firewood, hunting, collecting mushrooms, having a garden and owning a woodshed, a dog or a companion rodent. We demonstrate a significant increase in the seroprevalence of all three target viruses between 2002 and 2015, but no risk factors that we considered were significantly correlated with this increase. We conclude that the general exposure of residents in the Alps to these viruses has probably increased during the last decade. These results provide an early warning to public health authorities, and we suggest more detailed diagnostic and clinical investigations on suspected cases.
Platelets are emerging as a promising source of blood biomarkers for several pathologies, including cancer. New automated techniques for easier manipulation of platelets in the context of lab-on-a-chips could be of great support for liquid biopsy. Here, several polymeric materials were investigated for their behavior in terms of adhesion and activation of human platelets. Polymeric materials were selected among the most used in microfabrication (PDMS, PMMA and COC) and commercial and home-made resins for 3D printing technology with the aim to identify the most suitable for the realization of microdevices for human platelets isolation and analysis. To visualize adherent platelets and their activation state scanning, electron microscopy was used, while confocal microscopy was used for evaluating platelets’ features. In addition, atomic force microscopy was employed to further study platelets adherent to the polymeric materials. Polymers were divided in two main groups: the most prone to platelet adhesion and materials that cause few or no platelets to adhere. Therefore, different polymeric materials could be identified as suitable for the realization of microdevices aimed at capturing human platelets, while other materials could be employed for the fabrication of microdevices or parts of microdevices for the processing of platelets, without loss on surfaces during the process.
Tympanoplasty is indicated to repair tympanic membrane perforations in patients affected by hearing loss.We investigated the outcomes of unconventional microscopic approach to type 1 tympanoplasty with autologous platelet gel in tympanic membrane perforation. Considering that platelet gel improves reparation of cutaneous lesions, we evaluate the efficacy of platelet gel application in patients with a damage of a particular soft tissue, as tympanic membrane (Adler and Kent, 2002;Bhanot and Alex, 2002;Mann et al., 2001;Pierce et al., 1991). We treated a patient referred to Otorinolaryngology Clinic of S. Maria del Carmine Hospital, Rovereto (TN) with a diagnosis of tympanic membrane perforation and mixed left hearing loss who undergone to a type 1 tympanoplasty with platelet gel. Our primary outcome was tympanic index closure.We report a faster recovery in this patient treated with platelet gel as an outpatients procedure.In conclusion, platelet gel application in otosurgery, in outpatients treatment. is a noninvasive, safe technique to restore tympanic perforation. However, further prospective data are needed to confirm these preliminary results.
Background - Population data on the HLA system are important to several areas of medicine and science. HLA-A*, B*, C*, DRB1* and DQB1* allele and haplotype frequencies in 105 unrelated healthy Italian individuals from Lombardy were estimated. Methods - Commercial kits with sequence-specific primers designed to match single alleles were used for specific primer polymerase chain reactions (PCR-SSP) to determine HLA class I (HLA-A*, B* and C* loci) and class II (HLA-DRB1*, DQB1* loci) alleles. For HLA-DRB1* single allele-specific amplification and sequencing was also used separately, using a Protrans S4 commercial kit. Results - A total of 16 HLA-A*, 22 HLA-B*, 14 HLA-C*, 20 DRB1* and 12 DQB1* alleles showing a frequency >1% were identified at the four-digit level in the population. The highest frequency alleles included A*02:01 (13.3%), B*51:01 (9.5%), C*04:01 (20.5%), DRB1* 11:01 (13.8%) and DQB1*03:01 (33.8%). The most frequent extensive haplotype was A*01:01-C*07:01 B*08:01-DRB1*03:01-DQB1*02:01 with a haplotype frequency of 2.4%. Conclusions - The present findings could be useful to elucidate the genetic background of the population, and to provide data for HLA matching in clinical transplantation, information on the distribution of HLA genotypes in different populations for the development of peptidebased vaccines, and information for paternity diagnosis and on evolutionary factors such as genetic drift, migration and selection
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