Refractory myasthenia gravis: Characteristics of a portuguese cohort

Introduction: Some myasthenia gravis (MG) patients are refractory to conventional treatments. Methods: To describe the clinical features of refractory MG (RMG) and explore the association with human leukocyte antigen HLA-DRB1 alleles, a cohort study of 114 consecutive MG patients was performed. Patients were classified as RMG based on predefined criteria. Results: Twenty-two patients were found to have RMG (19.3%). There were no differences between non-RMG and RMG patients with respect to sex, age of onset, abnormal 3-Hz repetitive nerve stimulation, anti-acetylcholine receptor antibody positivity, thymectomy, thymoma or thymic hyperplasia, and polyautoimmunity. HLA-DRB1*03 was more frequent in the non-RMG vs. control population (P = 3 × 10⁻⁶). The HLA-DRB1*13 allele was less frequent in non-RMG patients compared with controls (P = 0.002), and less frequent in the non-RMG group compared with the RMG group (P = 0.003). Discussion: HLA-DRB1*03 was more common in non-RMG, and the HLA-DRB1*13 allele appeared to have a protective role, as reported previously in other autoimmune disorders. Muscle Nerve 60 : 188–191, 2019     

Detection of R337H, a germline TP53 mutation predisposing to multiple cancers, in asymptomatic women participating in a breast cancer screening program in Southern Brazil

Germline TP53 mutations predispose to a rare familial cancer syndrome, the Li-Fraumeni Syndrome (LFS), characterized by the early onset of multiple cancers including childhood adrenocortical carcinomas, sarcomas and brain tumors, and breast and colon cancer in young adults. An identical germline mutation at codon 337 in TP53 (R337H) has been shown to be causally related to an increased risk of multiple cancers in unrelated subjects with familial cancer risk in Southern Brazil. Here we have assessed the prevalence of R337H in 750 healthy women participating in a community-based breast cancer screening program in the area of Porto Alegre. The mutant was detected in two participants (0.3%) who were fourth-degree relatives and reported a familial history of cancer at multiple sites that did not match classical criteria for LFS and its variants. Testing in additional family members detected the mutation in three subjects, one of whom developed breast cancer at the age of 36. These findings indicate that R337H may be a low penetrance mutant which predisposes to multiple cancers and occurs in the population of Southern Brazil at a frequency 10-20 times higher than other TP53 mutants commonly associated with LFS.     

High 1,4-cis-polybutadiene by uranium catalysts, 2. Bulk and solution crystallization of polymers

Bulk isothermal crystallization kinetics of some highly tactic 1,4-cis-polybutadienes obtained with a new catalyst based on uranium derivatives were dilatometrically measured over a crystallization temperature (T_c) range from ?30 to 0°C. The corresponding experimental melting temperatures (T) of uranium polybutadiene range from 3 to 12,5°C. A relationship between the isothermal bulk half-crystallization time (t_1/2) at ?10°C and the molecular weight (MW) has been obtained. High MW fractions crystallize faster than low MW fractions as previously reported for 1,4-cis-polyisoprene. Uranium polybutadiene has been fractionated by crystallization. by cooling and stirring a dilute toluene solution. Under the same experimental conditions + rubber does not crystallize.     

Immunogenicity and reactogenicity of a combined adsorbed tetanus toxoid, low dose diphtheria toxoid, five component acellular pertussis and inactivated polio vaccine in six-year-old children

BACKGROUND: The objective of this study was to assess the immunogenicity and reactogenicity of the combined adsorbed tetanus toxoid, low dose diphtheria toxoid, 5-component acellular pertussis and inactivated polio vaccine (TdcP-IPV) as compared with a pediatric dose diphtheria formulation, combined with adsorbed tetanus toxoid and 3-component acellular pertussis (DTacP), in 6-year-old children who were immunized with 4 doses of diphtheria-tetanus-whole cell cellular pertussis (DTwcP) plus oral polio vaccine (OPV) before 2 years of age, according to the local Spanish vaccination calendar. METHODS: One hundred ninety-four healthy 6-year-old children were randomized to receive 1 dose of TdcP-IPV or 1 dose of DTacP and OPV. RESULTS: One month postvaccination, antidiphtheria and antitetanus titers were > or =0.1 IU/mL in 100% of patients in both study groups. TdcP-IPV reached 100% seroprotection rates against polio types 1, 2 and 3. In OPV recipients, these rates were 100, 100 and 96.8%, respectively. Seropositivity rates for pertussis toxin, filamentous hemagglutinin, pertactin and fimbrial components of the TdcP-IPV vaccine were 97.9, 89.6, 90.6 and 100%. The incidence of local and systemic reactions was 50.5 and 39.2% in the TdcP-IPV group and 59.4 and 38.5% in the DTacP plus OPV group, and no serious adverse events were reported. CONCLUSIONS: TdcP-IPV vaccine was shown to be immunogenic and safe when given as a booster in children 6 years of age who were primed with 4 doses of DTwcP and OPV.     

The roles of parathyroid hormone and calcitonin in bone remodeling: prospects for novel therapeutics

Inappropriate regulation of the bone resorption and bone formation processes that occur as a normal part of bone remodeling can lead to net bone loss, as found in osteoporosis. Parathyroid hormone (PTH) and calcitonin (CT) are two peptide hormones that play important roles in calcium homeostasis through their actions on osteoblasts (bone forming cells) and osteoclasts (bone resorbing cells), respectively. Paradoxically, even though genetic deletion of either PTH or CT produces mice with increased bone mass (presumably through different mechanisms), derivatives of both PTH and CT have now been approved for clinical use in the treatment of bone loss in osteoporosis. In this review, we focus on the biology and pharmacology of these two peptides. Specifically, we sequentially address the following three topics in detail: (1) the biological mechanisms of action of PTH and CT, focusing on data from in vitro studies and animal models; (2) the clinical utility of PTH and CT in treating osteoporosis, examining how their pharmacological efficacy correlates with our understanding of their biological mechanism of action; and (3) future prospects for combination therapy, alternative formulation of PTH and CT into oral and transdermal therapies, and replacement of PTH and CT with modified peptides or small molecules. The past four years have witnessed dramatic advances in each of these three areas, and the review places in context the challenges that lie ahead for this complicated, but clinically-relevant field.