The role of nasal CPAP in obstructive sleep apnoea syndrome due to mandibular hypoplasia.

Melnick Needles syndrome (MNS), Treacher Collins syndrome (TCS) and Pierre Robin syndrome (PRS) are congenital abnormalities with characteristic facial appearances that include micrognathia. A 20-year-old girl with MNS, a 16-year-old boy with TCS and a 12-year-old girl with PRS attended the sleep apnoea clinic at our institution at different times. Diagnostic sleep studies were initially performed on all three patients to confirm the diagnosis of obstructive sleep apnoea syndrome (OSAS). They subsequently commenced nasal CPAP (nCPAP) treatment and their progress was followed. A limited sleep study on the patient with MNS demonstrated moderate/severe OSAS with an AHI of 33 events/h. Commencement of nCPAP resulted in symptomatic improvement. Overnight oximetry in the patient with TCS showed repeated desaturation to SpO2<90%. Subsequent treatment by nCPAP almost completely abolished the desaturation events. Overnight polysomnography in the patient with PRS demonstrated severe OSAS with an AHI of 49 events/h. After 3 years of nCPAP therapy, this patient requested discontinuation of treatment. Subsequent polysomnography without nCPAP revealed an AHI of <5 events/h. The use of nCPAP in the patients with MNS and TCS resulted in effective control of their sleep abnormalities. Mandibular growth and enlargement of the posterior airway space led to resolution of OSAS in the patient with PRS. There is a definite role for nCPAP therapy in patients with congenital micrognathia and OSAS. The use of nCPAP may obviate the need for more invasive corrective surgery for OSAS and is not necessarily a life-long requirement.

Predictive validity of measurements of clinical competence using the team objective structured bedside assessment (TOSBA): assessing the clinical competence of final year medical students.

BACKGROUND: The importance of valid and reliable assessment of student competence and performance is gaining increased recognition. Provision of valid patient-based formative assessment is an increasing challenge for clinical teachers in a busy hospital setting. A formative assessment tool that reliably predicts performance in the summative setting would be of value to both students and teachers. AIM: This study explores the utility of the team objective structured bedside assessment (TOSBA), a novel ward-based formative assessment tool, in predicting student performance in the final clinical examination. METHODS: The performance of a cohort of final year students (n = 191) in the TOSBA was compared with their subsequent performance in the final examination. A comparison was also made between student performance in the existing formative assessment tool, the objective structured long examination record (OSLER) and the final examination. We also examined the relationship between the TOSBA and the components of the final examination using clustering around latent variables analysis. RESULTS: There was a clear relationship between student performance in the TOSBA and performance in the final examination (r(2) = 0.35). Student performance in the OSLER showed a poor relationship with performance in the final examination (r(2) = 0.15) compared with the TOSBA. The TOSBA results showed particular correlation with specific components of the final examination which were clinically based. CONCLUSION: TOSBA performance is a strong predictor of subsequent performance in the final examination. The clustering of the TOSBA with other assessments of clinical skills underlines its utility. Further research is required to determine whether performance in the TOSBA is predictive of subsequent performance during internship.

Tauroursodeoxycholic acid inhibits apoptosis induced by Z alpha-1 antitrypsin via inhibition of Bad.

UNLABELLED: Z alpha-1 antitrypsin (AAT) deficiency is a genetic disease associated with accumulation of misfolded AAT in the endoplasmic reticulum (ER) of hepatocytes. ZAAT-expressing cells display ER stress responses including nuclear factor kappaB activation and apoptosis. Using an in vitro model of ZAAT ER accumulation, we investigated the mechanism of ZAAT-mediated ER-induced apoptosis and evaluated methods to inhibit this process. Here we demonstrate that expression of ZAAT, but not normal MAAT, in HEK293 cells leads to cleavage and activation of caspase-4 and induces apoptosis that is characterized by activation of caspase-3 and caspase-7 and DNA fragmentation. Similar effects are also induced using the ER agonist thapsigargin. A caspase-4-specific short interfering RNA (siRNA) does not impair ZAAT-induced caspase-3/7 activation or cell death in these cells. However, inhibition studies performed using tauroursodeoxycholic acid (TUDCA) demonstrate its ability to inhibit caspase-4 and caspase-3/7 activation, mitochondrial cytochrome c release, and caspase-3 cleavage induced by ZAAT and to promote cell survival. The mechanism by which TUDCA (tauroursodeoxycholic acid) promotes cell survival in ZAAT-expressing cells involves phosphorylation and inactivation of the proapoptotic factor Bad. TUDCA is unable to rescue cells from apoptosis or phosphorylate Bad in the presence of LY294002, a selective P-I-3-kinase inhibitor. CONCLUSION: These data show that caspase-4 is not essential for ZAAT-induced apoptosis in HEK293 cells and implicates P-I-3-kinase and Bad as potential therapeutic targets for the liver disease associated with ZAAT deficiency.