Basement membrane collagen IV deficiency promotes abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a complex disease which is incompletely accounted for. Basement membrane (BM) Collagen IV (COL4A1/A2) is abundant in the artery wall, and several lines of evidence indicate a protective role of baseline COL4A1/A2 in AAA development. Using Col4a1/a2 hemizygous knockout mice (Col4a1/a2+/-, 129Svj background) we show that partial Col4a1/a2 deficiency augmented AAA formation. Although unchallenged aortas were morphometrically and biomechanically unaffected by genotype, explorative proteomic analyses of aortas revealed a clear reduction in BM components and contractile vascular smooth muscle cell (VSMC) proteins, suggesting a central effect of the BM in maintaining VSMCs in the contractile phenotype. These findings were translated to human arteries by showing that COL4A1/A2 correlated to BM proteins and VSMC markers in non-lesioned internal mammary arteries obtained from coronary artery bypass procedures. Moreover, in human AAA tissue, MYH11 (VSMC marker) was depleted in areas of reduced COL4 as assessed by immunohistochemistry. Finally, circulating COL4A1 degradation fragments correlated with AAA progression in the largest Danish AAA cohort, suggesting COL4A1/A2 proteolysis to be an important feature of AAA formation. In sum, we identify COL4A1/A2 as a critical regulator of VSMC phenotype and a protective factor in AAA formation.

Eight years of Legionnaires' disease transmission in travellers to a condominium complex in Las Vegas, Nevada.

Travel is a risk factor for Legionnaires' disease. In 2008, two cases were reported in condominium guests where we investigated a 2001 outbreak. We reinvestigated to identify additional cases and determine whether ongoing transmission resulted from persistent colonization of potable water. Exposures were assessed by matched case-control analyses (2001) and case-series interviews (2008). We sampled potable water and other water sources. Isolates were compared using sequence-based typing. From 2001 to 2008, 35 cases were identified. Confirmed cases reported after the cluster in 2001-2002 were initially considered sporadic, but retrospective case-finding identified five additional cases. Cases were more likely than controls to stay in tower 2 of the condominium [matched odds ratio (mOR) 6·1, 95% confidence interval (CI) 1·6-22·9]; transmission was associated with showering duration (mOR 23·0, 95% CI 1·4-384). We characterized a clinical isolate as sequence type 35 (ST35) and detected ST35 in samples of tower 2's potable water in 2001, 2002, and 2008. This prolonged outbreak illustrates the importance of striving for permanent Legionella eradication from potable water.

Anaesthetic morbidity at the University Hospital of the West Indies / Morbilidad anestésica en el Hospital Universitario de West Indies: un estudio transversal prospectivo

OBJECTIVE: There is little information on adverse anaesthetic outcomes from the Caribbean. The aim of this study was to investigate the occurrence of anaesthetic morbidity and mortality at the University Hospital of the West Indies (UHWI) and to identify possible risk factors. METHODS: All anaesthetic procedures at the UHWI were monitored for adverse events and patient outcomes for the 12-month period from March 2004 to February 2005. Possible risk factors for these adverse events were assessed using logistic regression. RESULTS: Of 3185 anaesthetic proceduress, the incidence of intra-operative events was 201 per 1000 (95% CI 187, 215); 151 per 1000 being cardiovascular and 26 per 1000 respiratory. Others included excess blood loss and equipment failure, hyperglycaemia, nausea and vomiting. Patients with intraoperative complications were three times more likely to have complications during recovery (OR = 3.35; 95% CI 2.59, 4.33, p < 0.001). The incidence of complications among paediatric patients was 139 per 1000 (95% CI 104, 174) intra-operatively and 58 per 1000 (95% CI 34, 81) during recovery. Risk factors for developing complications (p < 0.05) included age > 50 years, ASA status > II, prolonged anaesthesia, high surgical risk, general or combined anaesthetic techniques, senior anaesthetist, intubated patients and co-morbidities. There were 14 operative mortalities, none of which was anaesthesia-related. CONCLUSION: Anaesthetic complication rates at the UHWI are comparable to those in developed countries, except for higher paediatric complication rates and ICU admissions and lower rates of postoperative nausea and vomiting.

OBJETIVO: Existe poca información sobre resultados anestésicos adversos en el Caribe. El propósito del presente estudio fue investigar la manifestación de la morbilidad y la mortalidad anestésicas en el Hospital Universitario de West Indies (UHWI) e identificar los posibles factores de riesgo. MÉTODOS: Todos los procedimientos anestésicos en el UHWI fueron monitoreados en busca de eventos adversos y resultados con los pacientes, durante un período de 12 meses a partir de marzo del 2004. Los posibles factores de riesgo para estos eventos adversos fueron evaluados mediante regresión logística. RESULTADOS: De 3185 procedimientos anestésicos, la incidencia de eventos intraoperatorios fue de 201 por 1000 (95% CI 187, 215); siendo 151 por 1000 cardiovasculares y 26 por 1000 respiratorios. Otros incluyeron exceso en pérdida de sangre y fallo de equipos, hiperglicemia, náusea, y vómitos. Los pacientes con complicaciones intraoperatorias presentaron una probabilidad de complicaciones tres veces mayor en la fase de recuperación (OR = 3.35; 95% CI 2.59, 4.33, p < 0.001). La incidencia de complicaciones entre pacientes pediátricos fue 139 por 1000 (95% CI 104, 174) intraoperatoriamente y 58 por 1000 (95% CI 34, 81) durante la recuperación. Entre los factores de riesgo que desarrollaban complicaciones (p < 0.05) se hallaban: la edad > 50 años, estatus de ASA > II, anestesia prolongada, alto riesgo quirúrgico, técnicas anestésicas combinadas o generales, anestesiólogos de la tercera edad, pacientes entubados, y comorbilidades. Se produjeron 14 mortalidades operatorias, ninguna de las cuales guardó relación con la anestesia. CONCLUSIÓN: Las tasas de complicación anestésica en UHWI son comparables a las que se producen en países desarrollados, excepto por las tasas de complicación pediátrica más altas, mayor número de ingresos a las UCIs, y tasas más bajas de náuseas y vómitos postoperatorios.

Anaesthetic morbidity at the University Hospital of the West Indies.

OBJECTIVE: There is little information on adverse anaesthetic outcomes from the Caribbean. The aim of this study was to investigate the occurrence of anaesthetic morbidity and mortality at the University Hospital of the West Indies (UHWI) and to identify possible risk factors. METHODS: All anaesthetic procedures at the UHWI were monitored for adverse events and patient outcomes for the 12-month period from March 2004 to February 2005. Possible risk factors for these adverse events were assessed using logistic regression. RESULTS: Of 3185 anaesthetic procedures, the incidence of intra-operative events was 201 per 1000 (95% CI 187, 215); 151 per 1000 being cardiovascular and 26 per 1000 respiratory. Others included excess blood loss and equipment failure, hyperglycaemia, nausea and vomiting. Patients with intraoperative complications were three times more likely to have complications during recovery (OR = 3.35; 95% CI 2.59, 4.33, p < 0.001). The incidence of complications among paediatric patients was 139 per 1000 (95% CI 104, 174) intra-operatively and 58 per 1000 (95% CI 34, 81) during recovery. Risk factors for developing complications (p < 0.05) included age > 50 years, ASA status > or = II, prolonged anaesthesia, high surgical risk, general or combined anaesthetic techniques, senior anaesthetist, intubated patients and co-morbidities. There were 14 operative mortalities, none of which was anaesthesia-related CONCLUSION: Anaesthetic complication rates at the UHWI are comparable to those in developed countries, except for higher paediatric complication rates and ICU admissions and lower rates of postoperative nausea and vomiting.