Alveolar haemorrhage in anti-glomerular basement membrane disease without detectable antibodies by conventional assays

Anti-glomerular basement membrane (anti-GBM) disease represents the spectrum of disease attributable to circulating anti-GBM antibodies. While active anti-GBM disease in the absence of circulating anti-GBM antibodies has been described, it is considered rare with the use of current routinely available assays. We report four subjects with features consistent with active anti-GBM antibody disease without detectable antibodies by routinely available enzyme linked immunosorbent assay (ELISA) and immunoblot techniques. All were smokers who presented with diffuse alveolar haemorrhage, minimal renal involvement, and undetectable anti-GBM antibodies. Seronegative anti-GBM disease with predominant pulmonary involvement may be more common than previously appreciated and should be part of the differential diagnosis for otherwise unexplained diffuse alveolar haemorrhage. Renal biopsy with immunofluorescent studies should be considered in the diagnostic evaluation of such subjects, including those with idiopathic pulmonary haemosiderosis.

Adolescent substance use in the context of the family: a qualitative study of young people’s views on parent-child attachments, parenting style and parental substance use

Background: Adolescent substance use can place youth at risk of a range of poor outcomes. Few studies have attempted to explore in-depth young people’s perceptions of how familial processes and dynamics influence adolescent substance use.
Objectives: This paper aimed to explore risk and protective factors for youth substance use within the context of the family with a view to informing family based interventions.
Methods: Nine focus groups supplemented with participatory techniques were facilitated with a purposive sample of sixty-two young people (age 13-17 years) from post-primary schools across Northern Ireland. The data were transcribed verbatim and analysed using thematic analysis.
Results: Three themes emerged from the data: 1) parent-child attachments, 2) parenting style and 3) parental and sibling substance misuse. Parent-child attachment was identified as an important factor in protecting adolescents from substance use in addition to effective parenting particularly an authoritative style supplemented with parental monitoring and strong parent-child communication to encourage child disclosure. Family substance use was considered to impact on children’s substance use if exposed at an early age and the harms associated with parental substance misuse were discussed in detail. Both parent and child gender differences were cross-cutting themes.
Conclusion: Parenting programmes (tailored to mothers and fathers) may benefit young people via components on authoritative styles, parental monitoring, communication, nurturing attachments and parent-child conflict. Youth living with more complex issues, e.g. parental substance misuse, may benefit from programmes delivered beyond the family environment e.g. school based settings.

Sarcoidosis, alveolar β-actin and pulmonary fibrosis

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown aetiology. Proteins present within the alveolar space early in sarcoidosis disease may provide an insight into novel mechanisms for the development of fibrotic disease and in particular pulmonary fibrosis.

METHODS: A modified two-dimensional difference gel electrophoresis protocol was applied to the human bronchoalveolar lavage fluid (hBALF) of four patients with non-persistent pulmonary interstitial disease at 4-year follow-up (defined as mild disease) and four patients who developed pulmonary interstitial disease at 4-year follow-up (defined as severe disease). The protein β-actin was identified by LC-MS/MS from a preparative gel and found to be significantly elevated in early lavages from the severe disease group. To look at the potential pro-fibrotic effects of this protein, primary human pulmonary fibroblasts (CCD-19Lu) were treated with recombinant β-actin following which qPCR and ELISA assays were used to measure any effects.

RESULTS: We found that β-actin levels were significantly elevated in early hBALF samples in patients who subsequently developed severe disease when compared to the mild group. Treating primary human pulmonary fibroblasts with recombinant β-actin led to enhanced gene expression of the pro-fibrotic markers alpha smooth muscle actin and collagen 1 as well as the increased secretion of interleukin-13 and metalloproteinases 3 and 9.

CONCLUSION: Free β-actin within the lungs of sarcoidosis patients potentially may contribute to disease pathogenesis particularly in the context of abnormal remodelling and the development of pulmonary fibrosis.

The comparative utility of fluorescence in situ hybridization and reverse transcription-polymerase chain reaction in the diagnosis of alveolar rhabdomyosarcoma.

Fluorescence in situ hybridization (FISH) for FOXO1 gene rearrangement and reverse transcription-polymerase chain reaction (PCR) for PAX3/7-FOXO1 fusion transcripts have become routine ancillary tools for the diagnosis of alveolar rhabdomyosarcomas (ARMS). Here we summarize our experience of these adjunct diagnostic modalities at a tertiary center, presenting the largest comparative series of FISH and PCR for suspected or possible ARMS to date. All suspected or possible ARMS tested by FISH or PCR for FOXO1 rearrangement or PAX3/7-FOXO1 fusion transcripts over a 7-year period were included. FISH and PCR results were correlated with clinical and histologic findings. One hundred samples from 95 patients had FISH and/or PCR performed. FISH had higher rates of technical success (96.8 %) compared with PCR (88 %). Where both tests were utilized successfully, there was high concordance rate between them (94.9 %). In 24 histologic ARMS tested for FISH or PCR, 83.3 % were translocation-positive (all for PAX3-FOXO1 by PCR) and included 3 histologic solid variants. In 76 cases where ARMS was excluded, there were 3 potential false-positive cases with FISH but none with PCR. PCR had similar sensitivity (85.7 %) and better specificity (100 %) in aiding the diagnosis of ARMS, compared with FISH (85 and 95.8 %, respectively). All solid variant ARMS harbored FOXO1 gene rearrangements and PAX3-FOXO1 ARMS were detected to the exclusion of PAX7-FOXO1. In comparative analysis, both FISH and PCR are useful in aiding the diagnosis of ARMS and excluding its sarcomatous mimics. FISH is more reliable technically but has less specificity than PCR. In cases where ARMS is in the differential diagnosis, it is optimal to perform both PCR and FISH: both have similar sensitivities for detecting ARMS, but FISH may confirm or exclude cases that are technically unsuccessful with PCR, while PCR can detect specific fusion transcripts that may be useful prognostically.

Meningeal alveolar soft part sarcoma confirmed by characteristic ASPCR1-TFE3 fusion

Sarcoma metastatic to the brain is uncommon and rarely occurs as the initial manifestation of tumor. Alveolar soft part sarcoma (ASPS) is a rare but well-studied subtype of sarcoma. A 39-year-old man presented with seizures due to a left temporal meningeal-enhancing lesion with striking brain edema on MRI. The patient underwent neurosurgical resection for suspected meningioma. Histology showed large tumor cells clustering and forming small nests, in places with pseudoalveolar pattern. Diastase-resistant periodic acid-Schiff revealed very rare granular and rod-like cytoplasmic inclusions. Immunohistochemistry showed convincing positivity only with vimentin and smooth muscle actin. The histological features were strongly suggestive of ASPS. At the molecular level RT-PCR and sequencing analysis demonstrated ASPCR1-TFE3 fusion confirming the histological diagnosis of ASPS. There was no evidence of primary extracranial tumor by physical examination and on chest and abdominal CT scan 11 months after presentation. ASPS typically arise from the soft tissues of the extremities and develop multiple metastatic deposits usually with a long clinical course. This case may represent primary meningeal ASPS although metastatic deposit from an undiscovered primary site cannot be entirely excluded.

Influencia do meloxicam sobre a perda ossea alveolar em periodontite experimental: avaliaçao histometrica em ratos

GURGEL, Bruno Cesar de vasconcelos.Influencia do meloxicam sobre a perda ossea alveolar em periodontite experimental: avaliaçao histometrica em ratos. 2003.97f. Dissertaçao (Mestrado) - Universidade Estadual de Campinas. Faculdade de Odontologia de Piracicaba. Piracicaba, 2003. Disponivel em: . Acesso em: 04 out. 2010.

Correção de colapsos da crista alveolar com tecidos duros

Introdução: Uma adequada planificação é condição sine qua non para o êxito do tratamento com implantes. No entanto, nem sempre a colocação dos implantes na posição tridimensional ideal é, logo à partida, viável. Neste contexto, a correção dos colapsos da crista óssea com tecidos duros assume especial importância. Objetivos: O objetivo desta revisão narrativa é avaliar a eficácia dos diversos procedimentos existentes para aumento do rebordo com tecidos duros, de forma a facilitar a escolha do tratamento ideal. Materiais e Métodos: Pesquisou-se nas bases de dados MEDLINE, B-on e Google Académico. As palavras-chave utilizadas foram: “guided bone regeneration”, “ridge augmentation”, “seibert classification”, “alveolar bone splitting”, “horizontal bone augmentation” e “vertical bone augmentation”. Deu-se especial ênfase a revisões sistemáticas e meta-análises. A pesquisa foi limitada a artigos publicados em inglês, espanhol e em português até abril de 2016. Foram ainda consultados os livros “Tratado de Periodontia Clínica e Implantologia Oral” de Lindhe et al. (2005), “Implantes Dentais Contemporâneos” de Misch et al. (2009) e “Reabilitação com implantes endo-ósseos” de Alcoforado et al. (2008). Resultados: De um modo geral, todos os procedimentos analisados obtiveram altas taxas de sobrevivência aquando da reabilitação com implantes. No entanto, não houve diferenças significativas entre as diversas técnicas que possam levar a uma conclusão relevante sobre qual a melhor técnica a utilizar para este tipo de procedimento. Conclusão: Há evidências insuficientes para sugerir qual a técnica que deve ser preferida para o aumento de rebordo com tecidos duros, pelo que mais estudos são necessários.

Influencia do meloxicam sobre a perda ossea alveolar em periodontite experimental: avaliaçao histometrica em ratos

GURGEL, Bruno Cesar de vasconcelos.Influencia do meloxicam sobre a perda ossea alveolar em periodontite experimental: avaliaçao histometrica em ratos. 2003.97f. Dissertaçao (Mestrado) - Universidade Estadual de Campinas. Faculdade de Odontologia de Piracicaba. Piracicaba, 2003. Disponivel em: . Acesso em: 04 out. 2010.