Pediatric pulmonary arterial hypertension due to a novel homozygous GDF2 missense variant affecting BMP9 processing and activity.

Pulmonary arterial hypertension (PAH) is a rare and severe disorder characterized by progressive pulmonary vasculopathy. Growth differentiation factor (GDF)2 encodes the pro-protein bone morphogenetic protein (BMP) 9, activated after cleavage by endoproteases into an active mature form. BMP9, together with BMP10, are high-affinity ligands of activin receptor-like kinase 1 (ALK1) and BMP receptor type II (BMPR2). GDF2 mutations have been reported in idiopathic PAH with most patients being heterozygous carriers although rare homozygous cases have been described. The link between PAH occurrence and BMP9 or 10 expression level is still unclear. In this study, we describe a pediatric case of PAH also presenting with telangiectasias and epistaxis. The patient carries the novel homozygous GDF2 c.946A > G mutation, replacing the first arginine of BMP9's cleavage site (R316) by a glycine. We show that this mutation leads to an absence of circulating mature BMP9 and mature BMP9-10 heterodimers in the patient's plasma although pro-BMP9 is still detected at a similar level as controls. In vitro functional studies further demonstrated that the mutation R316G hampers the correct processing of BMP9, leading to the secretion of inactive pro-BMP9. The heterozygous carriers of the variant were asymptomatic, similarly to previous reports, reinforcing the hypothesis of modifiers preventing/driving PAH development in heterozygous carriers.

Field-induced glassy state in disordered cluster antiferromagnets.

We investigate the role of antiferromagnetic spin clusters on the glassiness induced by uniform and random fields. We consider an antiferromagnetic disordered model that is treated within the replica method, resulting in an effective single-cluster problem. Our results show that regimes of weak and intermediate disorder are suitable for highly unusual phenomena. For the case of a uniform field, cluster polarization can favor a cluster spin-glass state, i.e. the magnetic field increases the freezing temperature at intermediate disorders. In addition, random fields introduce local perturbations that allow uncompensated cluster states, supporting cluster freezing even at very weak disorders. The theoretical framework presented here can be useful for the understanding of phenomena observed in magnetic glassy systems that have spin clusters as building blocks instead of individual spins. In particular, we suggest that our results can help to explain the magnetic behaviour of the rare earth TbIn0.99Mn0.01O3, which has been recently proposed to be composed of antiferromagnetic clusters, presenting a field-induced increase of the freezing temperature.

Association between the 1858T allele of the protein tyrosine phosphatase nonreceptor type 22 and type 1 diabetes in a Brazilian population.

The 1858T allele of the protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene has been associated to diabetes in different populations. We investigated a possible relationship between this polymorphism and type 1 diabetes in a cohort of Brazilian patients. A significantly higher frequency of the 1858T allele was observed in diabetic patients (n = 211) than in control individuals (n = 241). Additionally, the heterozygote genotype was also increased in the diabetic group. No association was observed between the PTPN22 T allele and gender, or between T carriers and age of onset of T1D. This work describes for the first time a strong association of the 1858T allele with type 1 diabetes in a Brazilian population, reinforcing the role of this variant as an important susceptibility factor for this disease.

[Tetanus. Physiopathology and intensive care treatment]. / Tetano. Fisiopatologia e trattamento in terapia intensiva.

BACKGROUND: Tetanus as a topic illness is underlined on the basis of the increased cases as well as the appearance of new populations at risk of infection. The tetanospasmins of mechanism action is stressed in order to evaluate the etiopathogenetic role of common therapies as well as the new ones. Ten cases of serious infection personally observed are analysed. METHODS: The case records of ten tetanus patients treated in our Intensive Care Unit between 1986 and 1997 have been retrospectively analysed. The prognosis correlated to the seriousness of the case. The most common clinical symptoms on admission were trismus and dysphagia (100% of patients). In 70% of cases, the illness was considered serious enough to warrant the use of neuro-muscular blockers and controlled ventilation. Among the complications observed pulmonary problems had the highest incidence (90%), followed by cardio-vascular ones (80%). Respiratory infections were the most frequently observed (9 patients). Autonomic dysfunction was a constant feature in patients with severe forms of the illness. RESULTS: The observed mortality rate was 30%. It was higher in males at the extremes of the age range. CONCLUSIONS: In the light of the survival results as well as the most recent literature data, guidelines for the approach of serious tetanic patients are outline. It is underlined that therapy effectiveness is higher when from being a symptom therapy it becomes an etiopathogenetic therapy.

[Clinical aspects of long-term parenteral alimentation in the "short intestine syndrome". Clinical case]. / Aspetti dell'alimentazione parenterale a lungo termine nella sindrome da "intestino corto". Caso clinico.

A case of malabsorption syndrome (organic wasting, hypokaliaemia, metabolic acidosis, diarrhoea, hypochromic anaemia) following removal of 4 m of ileus for thrombophlebitis of the mesentery is described. In the first seven months, the patient was hospitalised five times to correct these imbalances by means of PA, with repeated venous incannulation. PA was continued at home each evening, together with heparin therapy (25,000 U calcic heparin/day). The patient later died following the appearance of serious venous thrombosis. The question of this complication and its prevention is discussed.

[Treatment of acute renal insufficiency in intensive care. Current perspectives with TPA and proxazole]. / Il trattamento dell'insufficienza renale acuta in rianimazione. Nuove prospettive con TPA e proxazolo.

A critical assessment is made of cases of ARF observed in a resuscitation department over the last three years. Reference is made to the physiopathological and pharmacological premises underlying the employment of a different therapeutic protocol, based on the maintenance of high diuresis with proxazol and the use of TPA to establish a nitrogen balance with a high cal/N ratio, coupled with the administration of histidine.