Transthyretin Amyloidosis: Chaperone Concentration Changes and Increased Proteolysis in the Pathway to Disease

Transthyretin amyloidosis is a conformational pathology characterized by the extracellular formation of amyloid deposits and the progressive impairment of the peripheral nervous system. Point mutations in this tetrameric plasma protein decrease its stability and are linked to disease onset and progression. Since non-mutated transthyretin also forms amyloid in systemic senile amyloidosis and some mutation bearers are asymptomatic throughout their lives, non-genetic factors must also be involved in transthyretin amyloidosis. We discovered, using a differential proteomics approach, that extracellular chaperones such as fibrinogen, clusterin, haptoglobin, alpha-1-anti-trypsin and 2-macroglobulin are overrepresented in transthyretin amyloidosis. Our data shows that a complex network of extracellular chaperones are over represented in human plasma and we speculate that they act synergistically to cope with amyloid prone proteins. Proteostasis may thus be as important as point mutations in transthyretin amyloidosis.

Clinical Outcomes and Genetic Expression Profile in Human Liver Graft Dysfunction During Ischemia/Reperfusion Injury

Introduction. This study aims to compare the molecular gene expression during ischemia reperfusion injury. Several surgical times were considered: in the beginning of the harvesting (T0), at the end of the cold ischemia period (T1), and after reperfusion (T2) and compared with graft dysfunction after liver transplant (OLT). Methods. We studied 54 patients undergoing OLT. Clinical, laboratory data, and histologic data (Suzuki classification) as well as the Survival Outcomes Following Liver Transplantation (SOFT) score were used and compared with the molecular gene expression of the following genes: Interleukin (IL)-1b, IL-6, tumor necrosis factor-a, perforin, E-selectin (SELE), Fas-ligand, granzyme B, heme oxygenase-1, and nitric oxide synthetase. Results. Fifteen patients presented with graft dysfunction according to SOFT criteria. No relevant data were obtained by comparing the variables graft dysfunction and histologic variables. We observed a statistically significant relation between SELE at T0 (P �� .013) and IL-1b at T0 (P �� .028) and early graft dysfunction. Conclusions. We conclude that several genetically determined proinflammatory expressions may play a critical role in the development of graft dysfunction after OLT.

Liver Depurative Techniques: A Single Liver Transplantation Center Experience

In a liver transplant (LT) center, treatments with Prometheus were evaluated. The main outcome considered was 1 and 6 months survival. Methods. During the study period, 74 patients underwent treatment with Prometheus; 64 were enrolled,with a mean age of 51 13 years; 47men underwent 212 treatments (mean, 3.02 per patient). The parameters evaluated were age, sex, laboratorial (liver enzymes, ammonia) and clinical (model for end-stage liver disease and Child-Turcotte-Pugh score) data. Results. Death was verified in 23 patients (35.9%) during the hospitalization period, 20 patients (31.3%) were submitted to liver transplantation, and 21 were discharged. LT was performed in 4 patients with acute liver failure (ALF, 23.7%), in 7 patients with acute on chronic liver failure (AoCLF, 43.7%), and in 6 patients with liver disease after LT (30%). Seven patients who underwent LT died (35%). In the multivariate analysis, older age (P �� .015), higher international normalized ratio (INR) (P �� .019), and acute liver failure (P �� .039) were independently associated with an adverse 1-month clinical outcome. On the other hand, older age (P �� .011) and acute kidney injury (P �� .031) at presentation were both related to worse 6-month outcome. For patients with ALF and AoCLF we did not observe the same differences. Conclusions. In this cohort, older age was the most important parameter defining 1- and 6-month survival, although higher INR and presence of ALF were important for 1-month survival and AKI for 6-month survival. No difference was observed between patients who underwent LT or did not have LT.

Infections After Liver Transplantation: A Retrospective, Single-Center Study

Objective. To access the incidence of infectious problems after liver transplantation (LT). Design. A retrospective, single-center study. Materials and Methods. Patients undergoing LT from January 2008 to December 2011 were considered. Exclusion criterion was death occurring in the first 48 hours after LT. We determined the site of infection and the bacterial isolates and collected and compared recipient���s variables, graft variables, surgical data, post-LT clinical data. Results. Of the 492 patients who underwent LT and the 463 considered for this study, 190 (Group 1, 41%) developed at least 1 infection, with 298 infections detected. Of these, 189 microorganisms were isolated, 81 (51%) gram-positive bacteria (most frequently Staphylococcus spp). Biliary infections were more frequent (mean time of 160.4 167.7 days after LT); from 3 months after LT, gram-negative bacteria were observed (57%). Patients with infections after LT presented lower aminotransferase levels, but higher requirements in blood transfusions, intraoperative vasopressors, hemodialysis, and hospital stay. Operative and cold ischemia times were similar. Conclusion. We found a 41% incidence of all infections in a 2-year follow-up after LT. Gram-positive bacteria were more frequent isolated; however, negative bacteria were commonly isolated later. Clinical data after LT were more relevant for the development of infections. Donors��� variables should be considered in future analyses.

Propylthiouracil Induced Pulmonary-Renal Syndrome: a Case Report.

Propylthiouracil (PTU) is known to induce antineutrophil cytoplasmatic antibody (ANCA) seropositivity; however, small vessel vasculitis (SVV) with pulmonary and renal involvement is rare. We present the case of an 81-year-old woman on PTU treatment due to toxic nodular goitre who developed alveolar hemorrhage and rapidly progressive glomerulonephritis. The authors highlight the importance of early recognising drug-induced pulmonary-renal syndrome (PRS) in order to avoid unnecessary tests, a delay in the diagnosis and evolution to end-stage kidney disease or life-threatening conditions.

Verrugas Anogenitais na Crian��a. Um Desafio Diagn��stico

As verrugas anogenitais s��o tumores epiteliais benignos da pele e mucosas resultantes da infe����o pelo papiloma v��rus humano. Observa-se uma preval��ncia crescente na popula����o pedi��trica, na qual ocorrem por transmiss��o vertical, auto ou hetero-inocula����o. O diagn��stico �� cl��nico e a biopsia reserva-se para casos duvidosos. Na maioria h�� uma regress��o espont��nea mas a taxa de recidiva �� elevada, mesmo sob terap��utica, pelo que a vigil��ncia cl��nica �� uma op����o v��lida. A poss��vel associa����o entre verrugas anogenitais e abuso sexual na crian��a constitui um desafio na pr��tica cl��nica. A maioria dos autores considera que o diagn��stico de abuso depende fundamentalmente da qualidade da anamnese, da experi��ncia dos profissionais envolvidos na avalia����o e do exame objetivo da crian��a. �� consensual que a probabilidade de abuso aumenta com a idade da crian��a, principalmente ap��s os 5 anos. Abaixo dos dois anos a transmiss��o n��o sexual do papiloma v��rus humano deve ser fortemente considerada na aus��ncia de sinais traum��ticos, de outra doen��a sexualmente transmiss��vel ou de hist��ria consistente de abuso. Contudo, em nenhuma idade a hip��tese de abuso sexual poder�� ser exclu��da, requerendo um seguimento cl��nico com pondera����o de todos os fatores mencionados.

Dermatose Febril. Um Diagn��stico a N��o Esquecer

Apresenta-se o caso de um doente de 46 anos, com coinfec����o VIH-1/VHC e cirrose hep��tica, internado por febre, prostra����o e astenia. Ao exame objetivo, observavam-se escassas p��stulas necr��ticas em base eritematosa acantonadas aos dedos das m��os e p��s com edema, dor e limita����o funcional dos mesmos e da articula����o t��bio-t��rsica esquerda. Analiticamente, apenas eleva����o ligeira da enzimologia hep��tica e da PCR. Admitiram-se as hip��teses diagn��sticas de endocardite, meningococc��mia ou gonococc��mia. Ap��s isolamento de Neisseria gonorrhoeae em hemocultura, iniciou-se ceftriaxone 1g/dia EV com melhoria cl��nica. A positividade da PCR para N.gonorrhoeae no exsudado orofar��ngeo confirmou o diagn��stico de gonococc��mia disseminada de ponto de partida orofar��ngeo. A gonorreia �� uma infe����o sexualmente transmitida causada pelo diplococo Gram negativo Neisseria gonorrhoeae. A gonococc��mia disseminada na forma da s��ndrome cl��ssica ���dermatite-artrite��� acompanha apenas 1-2% das infe����es mucosas. A gonorreia orofar��ngea �� geralmente assintom��tica em homens e mulheres, constituindo provavelmente um reservat��rio importante do agente. O aumento da incid��ncia de gonorreia torna este caso pertinente na pr��tica cl��nica actual do dermatologista.

Placas Assintom��ticas no Couro Cabeludo

A mucinose cut��nea focal �� um padr��o de rea����o histol��gica descrita em v��rias doen��as no qual existe uma deposi����o focal anormal de mucinas na derme. Os autores apresentam um caso de um doente de 62 anos de idade, com placas infiltradas assintom��ticas no couro cabeludo frontal e occipital, com tr��s meses de evolu����o. Bi��psias seriadas demostraram um infiltrado linfocit��rio moderado e deposi����o homog��nea de mucinas na derme, sem altera����es da epiderme, unidade pilosseb��cea, epidermotropismo ou granulomas. Investiga����es posteriores revelaram um adenocarcinoma prim��rio do pulm��o. A mucinose cut��nea focal pode ter um amplo espectro de apresenta����es cl��nicas. Relatamos este caso para ilustrar uma apresenta����o incomum de mucinose cut��nea focal no couro cabeludo e real��ar a import��ncia de excluir uma doen��a secund��ria associada. No melhor conhecimento dos autores este �� o primeiro caso relatado de uma poss��vel associa����o entre o adenocarcinoma do pulm��o e mucinose cut��nea.

Ovarian Ectopic Pregnancy in Adolescence

Ovarian pregnancy is one of the rarest types of extrauterine pregnancy. Its preoperative diagnosis remains a challenge since it presents quite similarly to tubal pregnancy and complicated ovarian cysts. Although in most cases, histology is necessary to confirm the diagnosis, we present an ovarian pregnancy in a teenager, correctly diagnosed during ultrasound examination.