Is a black eye a useful sign of facial fractures in patients with minor head injuries? A retrospective analysis in a level I trauma centre over 10 years

Orbital blunt trauma is common, and the diagnosis of a fracture should be made by computed tomographic (CT) scan. However, this will expose patients to ionising radiation. Our objective was to identify clinical predictors of orbital fracture, in particular the presence of a black eye, to minimise unnecessary exposure to radiation. A 10-year retrospective study was made of the medical records of all patients with minor head trauma who presented with one or two black eyes to our emergency department between May 2000 and April 2010. Each of the patients had a CT scan, was over 16 years old, and had a Glasgow Coma Score (GCS) of 13-15. The primary outcome was whether the black eye was a valuable predictor of a fracture. Accompanying clinical signs were considered as a secondary outcome. A total of 1676 patients (mean (SD) age 51 (22) years) and minor head trauma with either one or two black eyes were included. In 1144 the CT scan showed a fracture of the maxillofacial skeleton, which gave an incidence of 68.3% in whom a black eye was the obvious symptom. Specificity for facial fractures was particularly high for other clinical signs, such as diminished skin sensation (specificity 96.4%), diplopia or occulomotility disorders (89.3%), fracture steps (99.8%), epistaxis (95.5%), subconjunctival haemorrhage (90.4%), and emphysema (99.6%). Sensitivity for the same signs ranged from 10.8% to 22.2%. The most striking fact was that 68.3% of all patients with a black eye had an underlying fracture. We therefore conclude that a CT scan should be recommended for every patient with minor head injury who presents with a black eye.

Post-mortem whole body computed tomography of opioid (heroin and methadone) fatalities: frequent findings and comparison to autopsy

OBJECTIVE To investigate frequent findings in cases of fatal opioid intoxication in whole-body post-mortem computed tomography (PMCT). METHODS PMCT of 55 cases in which heroin and/or methadone had been found responsible for death were retrospectively evaluated (study group), and were compared with PMCT images of an age- and sex-matched control group. Imaging results were compared with conventional autopsy. RESULTS The most common findings in the study group were: pulmonary oedema (95 %), aspiration (66 %), distended urinary bladder (42 %), cerebral oedema (49 %), pulmonary emphysema (38 %) and fatty liver disease (36 %). These PMCT findings occurred significantly more often in the study group than in the control group (p < 0.05). The combination of lung oedema, brain oedema and distended urinary bladder was seen in 26 % of the cases in the study group but never in the control group (0 %). This triad, as indicator of opioid-related deaths, had a specificity of 100 %, as confirmed by autopsy and toxicological analysis. CONCLUSIONS Frequent findings in cases of fatal opioid intoxication were demonstrated. The triad of brain oedema, lung oedema and a distended urinary bladder on PMCT was highly specific for drug-associated cases of death. KEY POINTS Frequent findings in cases of fatal opioid intoxication were investigated. Lung oedema, brain oedema and full urinary bladder represent a highly specific constellation. This combination of findings in post-mortem CT should raise suspicion of intoxication.

The role of inducible nitric oxide synthase for interstitial remodeling of alveolar septa in surfactant protein D-deficient mice

Surfactant protein D (SP-D) modulates the lung's immune system. Its absence leads to NOS2-independent alveolar lipoproteinosis and NOS2-dependent chronic inflammation, which is critical for early emphysematous remodeling. With aging, SP-D knockout mice develop an additional interstitial fibrotic component. We hypothesize that this age-related interstitial septal wall remodeling is mediated by NOS2. Using invasive pulmonary function testing such as the forced oscillation technique and quasistatic pressure-volume perturbation and design-based stereology, we compared 29-wk-old SP-D knockout (Sftpd(-/-)) mice, SP-D/NOS2 double-knockout (DiNOS) mice, and wild-type mice (WT). Structural changes, including alveolar epithelial surface area, distribution of septal wall thickness, and volumes of septal wall components (alveolar epithelium, interstitial tissue, and endothelium) were quantified. Twenty-nine-week-old Sftpd(-/-) mice had preserved lung mechanics at the organ level, whereas elastance was increased in DiNOS. Airspace enlargement and loss of surface area of alveolar epithelium coexist with increased septal wall thickness in Sftpd(-/-) mice. These changes were reduced in DiNOS, and compared with Sftpd(-/-) mice a decrease in volumes of interstitial tissue and alveolar epithelium was found. To understand the effects of lung pathology on measured lung mechanics, structural data were used to inform a computational model, simulating lung mechanics as a function of airspace derecruitment, septal wall destruction (loss of surface area), and septal wall thickening. In conclusion, NOS2 mediates remodeling of septal walls, resulting in deposition of interstitial tissue in Sftpd(-/-). Forward modeling linking structure and lung mechanics describes the complex mechanical properties by parenchymatous destruction (emphysema), interstitial remodeling (septal wall thickening), and altered recruitability of acinar airspaces.

Modifying Post-Operative Medical Care after EBV Implant May Reduce Pneumothorax Incidence.

OBJECTIVE Endoscopic lung volume reduction (ELVR) with valves has been shown to improve COPD patients with severe emphysema. However, a major complication is pneumothoraces, occurring typically soon after valve implantation, with severe consequences if not managed promptly. Based on the knowledge that strain activity is related to a higher risk of pneumothoraces, we asked whether modifying post-operative medical care with the inclusion of strict short-term limitation of strain activity is associated with a lower incidence of pneumothorax. METHODS Seventy-two (72) emphysematous patients without collateral ventilation were treated with bronchial valves and included in the study. Thirty-two (32) patients received standard post-implantation medical management (Standard Medical Care (SMC)), and 40 patients received a modified medical care that included an additional bed rest for 48 hours and cough suppression, as needed (Modified Medical Care (MMC)). RESULTS The baseline characteristics were similar for the two groups, except there were more males in the SMC cohort. Overall, ten pneumothoraces occurred up to four days after ELVR, eight pneumothoraces in the SMC, and only two in the MMC cohorts (p=0.02). Complicated pneumothoraces and pneumothoraces after upper lobe treatment were significantly lower in MMC (p=0.02). Major clinical outcomes showed no significant differences between the two cohorts. CONCLUSIONS In conclusion, modifying post-operative medical care to include bed rest for 48 hours after ELVR and cough suppression, if needed, might reduce the incidence of pneumothoraces. Prospective randomized studies with larger numbers of well-matched patients are needed to confirm the data.

Pulmonary lymphangioleiomyomatosis: analysis of disease manifestation by region-based quantification of lung parenchyma

PURPOSE Lymphangioleiomyomatosis (LAM) is characterized by proliferation of smooth muscle tissue that causes bronchial obstruction and secondary cystic destruction of lung parenchyma. The aim of this study was to evaluate the typical distribution of cystic defects in LAM with quantitative volumetric chest computed tomography (CT). MATERIALS AND METHODS CT examinations of 20 patients with confirmed LAM were evaluated with region-based quantification of lung parenchyma. Additionally, 10 consecutive patients were identified who had recently undergone CT imaging of the lung at our institution, in which no pathologies of the lung were found, to serve as a control group. Each lung was divided into three regions (upper, middle and lower thirds) with identical number of slices. In addition, we defined a "peel" and "core" of the lung comprising the 2 cm subpleural space and the remaining inner lung area. Computerized detection of lung volume and relative emphysema was performed with the PULMO 3D software (v3.42, Fraunhofer MEVIS, Bremen, Germany). This software package enables the quantification of emphysematous lung parenchyma by calculating the pixel index, which is defined as the ratio of lung voxels with a density <-950HU to the total number of voxels in the lung. RESULTS Cystic changes accounted for 0.1-39.1% of the total lung volume in patients with LAM. Disease manifestation in the central lung was significantly higher than in peripheral areas (peel median: 15.1%, core median: 20.5%; p=0.001). Lower thirds of lung parenchyma showed significantly less cystic changes than upper and middle lung areas combined (lower third: median 13.4, upper and middle thirds: median 19.0, p=0.001). CONCLUSION The distribution of cystic lesions in LAM is significantly more pronounced in the central lung compared to peripheral areas. There is a significant predominance of cystic changes in apical and intermediate lung zones compared to the lung bases.

A cohort study of occupational asbestos-exposure related neoplasms in Texas Gulf Coast area

A cohort study was conducted in Texas and Louisiana Gulf Coast area on individual workers who have been exposed to asbestos for 15 years or more. Most of these workers were employed in petrochemical industries. Of the 15,742 subjects initially selected for the cohort study, 3,258 had positive chest X-ray findings believed to be related to prolonged asbestos exposure. These subjects were further investigated. Their work out included detailed medical and occupational history, laboratory tests and spirometry. One thousand eight-hundred and three cases with positive chest X-ray findings whose data files were considered complete at the end of May 1986 were analyzed and their findings included in this report.^ The prevalence of lung cancer and cancer of the following sights: skin, stomach, oropharyngeal, pancreas and kidneys were significantly increased when compared to data from Connecticut Tumor Registry. The prevalence of other chronic conditions such as hypertension, emphysema, heart disease and peptic ulcer was also significantly high when compared to data for the U.S. and general population furnished by the National Center for Health Statistics (NCHS). In most instances the occurrence of cancer and the chronic ailment previously mentioned appeared to follow 15-25 years of exposure to asbestos. ^

Inactive conformation of the serpin α1-antichymotrypsin indicates two-stage insertion of the reactive loop: Implications for inhibitory function and conformational disease

The serpins are a family of proteinase inhibitors that play a central role in the control of proteolytic cascades. Their inhibitory mechanism depends on the intramolecular insertion of the reactive loop into β-sheet A after cleavage by the target proteinase. Point mutations within the protein can allow aberrant conformational transitions characterized by β-strand exchange between the reactive loop of one molecule and β-sheet A of another. These loop-sheet polymers result in diseases as varied as cirrhosis, emphysema, angio-oedema, and thrombosis, and we recently have shown that they underlie an early-onset dementia. We report here the biochemical characteristics and crystal structure of a naturally occurring variant (Leu-55–Pro) of the plasma serpin α1-antichymotrypsin trapped as an inactive intermediate. The structure demonstrates a serpin configuration with partial insertion of the reactive loop into β-sheet A. The lower part of the sheet is filled by the last turn of F-helix and the loop that links it to s3A. This conformation matches that of proposed intermediates on the pathway to complex and polymer formation in the serpins. In particular, this intermediate, along with the latent and polymerized conformations, explains the loss of activity of plasma α1-antichymotrypsin associated with chronic obstructive pulmonary disease in patients with the Leu-55–Pro mutation.

Avaliação do tratamento com um inibidor para serinoprotease em modelo experimental de enfisema induzido por exposição à fumaça de cigarro

Introdução: Demonstramos previamente que em modelo experimental de enfisema pulmonar induzido por instilação de elastase, o inibidor de serinoprotease rBmTI-A promoveu a melhora da destruição tecidual em camundongos. Considerando que o tabagismo é o principal fator de risco para o desenvolvimento da Doença Pulmonar Obstrutiva Crônica (DPOC) e que o modelo de exposição à fumaça de cigarro é considerado o que melhor mimetiza esta doença em humanos, este estudo teve por objetivo verificar a ação do inibidor para serinoproteases rBmTI-A sobre os processos fisiopatológicos envolvidos no desenvolvimento do enfisema pulmonar, em modelo de exposição ao tabaco. Métodos: Para a indução do enfisema pulmonar, os animais foram expostos à fumaça de cigarro (duas vezes ao dia/ 30 minutos/ 5 dias por semana/ durante 12 semanas), e os animais controle permaneceram expostos ao ar ambiente. Dois protocolos de tratamento com o inibidor rBmTI-A foram realizados. No primeiro, os animais receberam duas administrações do inibidor rBmTI-A ou de seu veículo (Solução Salina 0,9%) por via intranasal, sendo a primeira após 24h do término das exposições ao cigarro e outra, 7 dias após à primeira instilação do inibidor. No segundo protocolo, os animais receberam 3 administrações do inibidor rBmTI-A, durante o tempo de exposição (1ª dose: 24h antes do início da exposição à fumaça de cigarro; 2ª dose: um mês após o início da exposição; 3ª dose: dois meses após o início). Após o término dos protocolos de exposição e tratamento, os animais foram submetidos aos procedimentos para coleta dos dados de mecânica respiratória e avaliação do Intercepto Linear Médio (Lm). Para o segundo protocolo, realizamos também as medidas para quantificação de fibras de colágeno e elástica, da densidade de células positivas para MAC-2, MMP-12 e 9, TIMP-1, Gp91phox e TNFalfa; no parênquima através de imunohistoquímica, contagem de células polimorfonucleares além da expressão gênica de MMP-12 e 9 no pulmão através de RT-qPCR. Resultados e Discussão: O tratamento com o inibidor para serinoprotease rBmTI-A atenuou o desenvolvimento do enfisema pulmonar apenas no segundo protocolo, quando foi administrado durante a exposição à fumaça de cigarro. Embora os grupos Fumo-rBmTIA e Fumo-VE apresentem aumento de Lm comparados aos grupos controles, houve uma redução deste índice no grupo Fumo-rBmTIA comparado ao grupo Fumo-VE. O mesmo comportamento foi observado para as análises de proporção em volume de fibras de elástica e colágeno no parênquima. Além disto, observamos aumento de macrófagos, MMP-12, MMP-9 e TNFalfa; nos grupos expostos à fumaça de cigarro, mas o tratamento com o inibidor rBmTI-A diminuiu apenas a quantidade de células positivas para MMP-12. Na avaliação da expressão gênica para MMP-12 e 9, não observamos diferença entre os grupos experimentais e o mesmo comportamento foi observado para a quantidade de células polimorfonucleares no parênquima. Além disso, observamos aumento de GP91phox e TIMP-1 nos grupos tratados com rBmTIA. Conclusões: Tais resultados sugerem que o inibidor rBmTI-A não foi efetivo como tratamento da lesão após a doença instalada. Entretanto, atenuou o desenvolvimento da doença quando administrado durante a indução do enfisema, possivelmente através do aumento de GP91phox e TIMP-1, acompanhados pela diminuição de MMP-12.

STRUCTURAL AND FUNCTIONAL CORRELATES OF EXERCISE VENTILATORY INEFFICIENCY IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS WITH MILD-TO-MODERATE SPIROMETRIC ABNORMALITIES

Background: Individuals with chronic obstructive pulmonary disease (COPD) have higher than normal ventilatory equivalents for carbon dioxide (VE/VCO2) during exercise. There is growing evidence that emphysema on thoracic computed tomography (CT) scans is associated with poor exercise capacity in COPD patients with only mild-to-moderate airflow obstruction. We hypothesized that emphysema is an underlying cause of microvascular dysfunction and ventilatory inefficiency, which in turn contributes to reduced exercise capacity. We expected ventilatory inefficiency to be associated with a) the extent of emphysema; b) lower diffusing capacity for carbon monoxide; c) a reduced pulmonary blood flow response to exercise; and d) reduced exercise capacity. Methods: In a cross-sectional study, 19 subjects with mild-to-moderate COPD (mean ± SD FEV1= 82 ± 13% predicted, 12 GOLD grade 1) and 26 age-, sex-, and activity-matched controls underwent a ramp-incremental symptom-limited exercise test on a cycle ergometer. Ventilatory inefficiency was assessed by the minimum VE/VCO2 value (nadir). A subset of subjects also completed repeated constant work rate exercise bouts with non-invasive measurements of pulmonary blood flow. Emphysema was quantified as the percentage of attenuation areas below -950 Housefield Units on CT scans. An electronic scoresheet was used to keep track of emphysema sub-types. Results: COPD subjects typically had centrilobular emphysema (76.8 ± 10.1% of total emphysema) in the upper lobes (upper/lower lobe ratio= 0.82 ± 0.04). They had lower peak oxygen uptake (VO2), higher VE/VCO2 nadir and greater dyspnea scores than controls (p<0.05). Lower peak O2 and worse dyspnea were found in COPD subjects with VE/VCO2 nadirs ≥ 30. COPD subjects had blunted increases in pulmonary blood flow from rest to iso-VO2 exercise (p<0.05). Higher VE/VCO2 nadir in COPD subjects correlated with emphysema severity (r= 0.63), which in turn correlated with reduced lung diffusing capacity (r= -0.72) and blunted changes in pulmonary blood flow from rest to exercise (r= -0.69) (p<0.01). Conclusions: Ventilation “wasted” in emphysematous areas is associated with reduced exercise ventilatory efficiency in mild-to-moderate COPD. Exercise ventilatory inefficiency links structure (emphysema) and function (gas transfer) to a key clinical outcome (reduced exercise capacity) in COPD patients with modest spirometric abnormalities.

In vivo models of lung neutrophil activation. Comparison of mice and hamsters

BACKGROUND: Evidence suggests that both the migration and activation of neutrophils into the airway is of importance in pathological conditions such as pulmonary emphysema. In the present study, we describe in vivo models of lung neutrophil infiltration and activation in mice and hamsters. RESULTS: BALB/c and C57BL/6 mice were intranasally treated with lipopolysaccharide (0.3 mg/kg). Twenty-four hours after, animals were treated intranasally with N-Formyl-Met-Leu-Phe (0 to 5 mg/kg). Golden Syrian hamsters were treated intratracheally with 0.5 mg/kg of lipopolysaccharide. Twenty-four hours after, animals were treated intratracheally with 0.25 mg/kg of N-Formyl-Met-Leu-Phe. Both mice and hamster were sacrificed two hours after the N-Formyl-Met-Leu-Phe application. In both BALB/c and C57BL/6 mice, a neutrophil infiltration was observed after the sequential application of lipopolysaccharide and N-Formyl-Met-Leu-Phe. However, 5 times less neutrophil was found in C57BL/6 mice when compared to BALB/c mice. This was reflected in the neutrophil activation parameters measured (myeloperoxidase and elastase activities). Despite the presence of neutrophil and their activation status, no lung haemorrhage could be detected in both strains of mice. When compared with mice, the lung inflammation induced by the sequential application of lipopolysaccharide and N-Formyl-Met-Leu-Phe was much greater in the hamster. In parallel with this lung inflammation, a significant lung haemorrhage was also observed. CONCLUSIONS: Both mouse and hamster can be used for pharmacological studies of new drugs or other therapeutics agents that aimed to interfere with neutrophil activation. However, only the hamster model seems to be suitable for studying the haemorrhagic lung injury process

Chronic respiratory diseases and quality of life in elderly nursing home residents

Few studies have assessed the quality of life (QOL) related to chronic respiratory diseases in the elderly. In the framework of the geriatric study on the health effects of air quality in elderly care centers (GERIA) study, a questionnaire was completed by elderly subjects from 53 selected nursing homes. It included various sections in order to assess respiratory complaints, QOL (World Health Organization QOL (WHOQOL)-BREF), and the cognitive and depression status. The outcome variables were the presence of a score lower than 50 (<50) in each of the WHOQOL-BREF domains (physical health, psychological health, social relationships, and environmental health). Chronic bronchitis, frequent cough, current wheezing, asthma, and allergic rhinitis were considered as potential risk factors. The surveyed sample was (n = 887) 79% female, with a mean age of 84 years (SD: 7 years). In the multivariable analysis, a score of <50 in the physical domain was associated with wheezing in the previous 12 months (odds ratio (OR): 2.03, confidence interval (CI): 1.25-3.31) and asthma (OR: 1.95, CI: 1.12-3.38). The psychological domain was related with a frequent cough (OR: 1.43, CI: 0.95-2.91). A score of <50 in the environmental domain was associated with chronic bronchitis (OR: 2.89, CI: 1.34-6.23) and emphysema (OR: 3.89, CI: 1.27-11.88). In view of these findings, the presence of respiratory diseases seems to be an important risk factor for a low QOL among elderly nursing home residents.

Pneumonia por Pneumocystis Jirovecii complicada por pneumotórax, pneumomediastino e enfisema subcutâneo

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