Ion and fluid transport properties of small airways in cystic fibrosis

RATIONALE: Small airways constitute a major site of pathology in cystic fibrosis (CF) and provide most of the surface area of the conducting airways of the lung. Little is known, however, about the impact of CF on ion and fluid transport in small (bronchiolar) airways. OBJECTIVES: To describe the ion and fluid transport properties of CF bronchiolar epithelium. METHODS: Primary cultures of human bronchial and bronchiolar (non-CF and CF) epithelial cells were obtained. The bioelectric properties were studied in Ussing chambers and the airway surface liquid (ASL) height was measured with confocal microscopy. MAIN RESULTS: Primary cultures of DeltaF508 CF bronchiolar epithelial cells displayed higher transepithelial resistance than non-CF cultures, whereas baseline short circuit current and amiloride-inhibitable short circuit current were similar in both preparations. The ASL height was significantly smaller in CF compared with non-CF preparations. In the presence of amiloride, addition of forskolin increased short circuit current in non-CF but not in CF bronchiolar cultures, and the ATP-induced increase in short circuit current was lower in CF than in non-CF cultures. Non-CF bronchiolar preparations displayed larger short circuit current and fluid secretion in responses to forskolin than non-CF bronchial preparations, suggesting that CFTR-dependent Cl(-) transport may play a more important role in the regulation of fluid transport in small airways than in large airways. CONCLUSION: In CF small airways, defective Cl(-) secretion combined with unregulated (persistent) Na(+) absorption results in ASLdepletion.     

Anti-topoisomerase I antibodies in systemic lupus erythematosus as a marker of severe nephritis

The authors report nine patients with systemic lupus erythematosus associated with anti-topoisomerase I antibodies (ELISA test) without features of systemic sclerosis. These antibodies were correlated with the disease activity and might be a marker of the severity of the closely related to difusse proliferative glomerulonephritis.     

Increased risk of pre-eclampsia and fetal death in HIV-infected pregnant women receiving highly active antiretroviral therapy

BACKGROUND: Pre-eclampsia and/or fetal death have increased sharply in HIV-infected pregnant women receiving HAART. METHODS: The occurrence of pre-eclampsia or fetal death was analysed in women who delivered after at least 22 weeks of gestation for all women (January 2001 until July 2003) and for HIV-infected women (November 1985 until July 2003). RESULTS: In 2001, 2002 and 2003, the rates per 1000 deliveries of pre-eclampsia and fetal death, respectively, remained stable in all pregnant women at 25.4, 31.9 and 27.7 (P = 0.48) and 4.8, 5.8, and 5.0 (P = 0.89) (n = 8768). In 1985-2000 (n = 390) to 2001-2003 (n = 82), rates per 1000 deliveries in HIV-infected women rose from 0.0 to 109.8 (P < 0.001) for pre-eclampsia and from 7.7 to 61.0 (P < 0.001) for fetal death. In all pregnant women, factors associated with pre-eclampsia or fetal death were multiple gestation [adjusted odds ratio (OR) 3.6; 95% confidence interval (CI), 2.3-5.6; P < 0.001], HIV infection (adjusted OR, 4.9; 95% CI, 2.4-10.1; P < 0.001), multiparity (adjusted OR, 0.76; 95% CI, 0.58-0.98; P = 0.040) and tobacco smoking (adjusted OR, 0.65; 95% CI, 0.46-0.90; P = 0.010). The use of HAART prior to pregnancy (adjusted OR, 5.6; 95% CI, 1.7-18.1; P = 0.004) and tobacco smoking (adjusted OR, 0.183; 95% CI, 0.054-0.627; P = 0.007) were risk factors in HIV-infected women. CONCLUSIONS: HIV infection treated with HAART prior to pregnancy was associated with a significantly higher risk for pre-eclampsia and fetal death.     

Inflammation and disability as risk factors for mortality in elderly acute care patients

Although the role of inflammation has been studied in specific diseases or in community living elderly, data in hospitalized acute care elderly patients are scarce. The present study was designed to determine the predictive value of sociodemographic, clinical and biological factors for mortality in acute care geriatric wards. Retrospective study was conducted in two acute care wards in a university-based geriatric hospital with elderly patients (n=224) consecutively admitted to acute care wards with available medical files. Sociodemographic variables, primary medical diagnosis and number of associated conditions, dementia, depression, pressure sores, functional status (measure by the activities of daily living=ADL scale), weight, and plasma levels of albumin, transthyretin, C-reactive protein (CRP) and orosomucoid were recorded at admission. Patients who died in the acute care wards were compared to those who survived. The mean length of stay was 16+/-13 days; mortality was 12%. Univariate analysis revealed that disability, no anti-depressant drug, pressure ulcers, a higher number of associated conditions, living with another person, and biological markers of malnutrition (albumin <35g/l, transthyretin <200mg/l) and inflammation (CRP < or =30mg/l, orosomucoid > or =1.25g/l) were significantly associated with an increase in the risk of death. The logistic regression model retained CRP > or =30mg/l (odds ratio (OR)=3.72, 95% confidence interval (CI)=1.34-10.31; p=0.009) and disability for at least one ADL item (OR=2.16, 95% CI=1.55-2.99; p<0.001) as independent risk factors for death. We conclude that CRP and disability are strong independent risk factors for death in this population, and special attention should be paid to these patients in an integrated therapeutic approach to geriatric care.     

Airway transplantation: a challenge for regenerative medicine

After more than 50 years of research, airway transplantation remains a major challenge in the fields of thoracic surgery and regenerative medicine. Five principal types of tracheobronchial substitutes, including synthetic prostheses, bioprostheses, allografts, autografts and bioengineered conduits have been evaluated experimentally in numerous studies. However, none of these works have provided a standardized technique for the replacement of the airways. More recently, few clinical attempts have offered encouraging results with ex vivo or stem cell–based engineered airways and tracheal allografts implanted after heterotopic revascularization. In 1997, we proposed a novel approach: the use of aortic grafts as a biological matrix for extensive airway reconstruction. In vivo regeneration of epithelium and cartilage were demonstrated in animal models. This led to the first human applications using cryopreserved aortic allografts that present key advantages because they are available in tissue banks and do not require immunosuppressive therapy. Favorable results obtained in pioneering cases have to be confirmed in larger series of patients with extensive tracheobronchial diseases.     

FDG PET during radiochemotherapy is predictive of outcome at 1 year in non-small-cell lung cancer patients: a prospective multicentre study (RTEP2)

Purpose

To assess prospectively the prognostic value of FDG PET/CT during curative-intent radiotherapy (RT) with or without concomitant chemotherapy in patients with non-small-cell lung cancer (NSCLC).

Methods

Patients with histological proof of invasive localized NSCLC and evaluable tumour, and who were candidates for curative-intent radiochemotherapy (RCT) or RT were preincluded after providing written informed consent. Definitive inclusion was conditional upon significant FDG uptake before RT (PET₁). All included patients had a FDG PET/CT scan during RT (PET₂, mean dose 43 Gy) and were evaluated by FDG PET/CT at 3 months and 1 year after RT. The main endpoint was death (from whatever cause) or tumour progression at 1 year.

Results

Of 77 patients preincluded, 52 were evaluable. Among the evaluable patients, 77 % received RT with induction chemotherapy and 73 % RT with concomitant chemotherapy. At 1 year, 40 patients (77 %) had died or had tumour progression. No statistically significant association was found between stage (IIIB vs. other), histology (squamous cell carcinoma vs. other), induction or concomitant chemotherapy, and death/tumour progression at 1 year. The SUV_max in the PET₂ scan was the single variable predictive of death or tumour progression at 1 year (odds ratio 1.97, 95 % CI 1.25 – 3.09, p?=?0.003) in multivariate analysis. The area under the receiver operating characteristic curve was 0.85 (95 % CI 0.73 – 0.94, p?<?10^?4). A SUV_max value of 5.3 in the PET₂ scan yielded a sensitivity of 70 % and a specificity of 92 % for predicting tumour progression or death at 1 year.

Conclusion

This prospective multicentre study demonstrated the prognostic value in terms of disease-free survival of SUV_max assessed during the 5th week of curative-intent RT or RCT in NSCLC patients (NCT01261598; RTEP2 study).     

Real-time PCR measurement of persistence of Bordetella pertussis DNA in nasopharyngeal secretions during antibiotic treatment of young children with pertussis

We used real-time PCR to examine the persistence of Bordetella pertussis DNA in serial nasopharyngeal aspirates from 22 children treated for pertussis. After 5 days of treatment, PCR was positive for all 21 assessable patients. After 14 and 21 days, PCR was still positive for 83% (10/12) and 66% (4/6) of assessable patients, respectively. One patient was tested 1 month after treatment initiation, and B. pertussis DNA was still detectable. Quantitative analysis showed that the DNA concentration diminished during treatment in all except one case. The PCR cycle threshold at which B. pertussis DNA became detectable increased by a mean of 1.7 cycles per day (range, 0.86 to 3.68 cycles per day). Real-time PCR can thus be used to diagnose pertussis in young children for up to 3 weeks after treatment initiation. Its potential value for assessing the treatment outcome remains to be determined.