Finding evidence to support airway clearance techniques in cystic fibrosis

Chest physiotherapy, aiming to clear bronchopulmonary secretions, has become a mainstay in the respiratory management of cystic fibrosis (CF). Early diagnosis and new therapeutic interventions have dramatically improved the outlook for patients with this disorder and it is no longer a disease of childhood. Along with these changes chest physiotherapy has also progressed, with the development of several treatment modalities that are more effective and can be performed by the patient without assistance. This allows older children and adults with CF to lead more normal and independent lifestyles. Despite this progress questions remain regarding the efficacy and consequences of airway clearance techniques, the scientific evidence available to support the selection of the most appropriate treatment modality and, not least, the problems associated with the treatment-related burden that is placed on patients and their families.     

Coordinated clearance of periciliary liquid and mucus from airway surfaces

Airway surface liquid is comprised of mucus and an underlying, watery periciliary liquid (PCL). In contrast to the well-described axial transport of mucus along airway surfaces via ciliary action, theoretical analyses predict that the PCL is nearly stationary. Conventional and confocal microscopy of fluorescent microspheres and photoactivated fluorescent dyes were used with well-differentiated human tracheobronchial epithelial cell cultures exhibiting spontaneous, radial mucociliary transport to study the movements of mucus and PCL. These studies showed that the entire PCL is transported at approximately the same rate as mucus, 39.2+/-4.7 and 39.8+/-4.2 micrometer/sec, respectively. Removing the mucus layer reduced PCL transport by > 80%, to 4.8+/-0.6 micrometer/sec, a value close to that predicted from theoretical analyses of the ciliary beat cycle. Hence, the rapid movement of PCL is dependent upon the transport of mucus. Mucus-dependent PCL transport was spatially uniform and exceeded the rate expected for pure frictional coupling with the overlying mucus layer; hence, ciliary mixing most likely accelerates the diffusion of momentum from mucus into the PCL. The cephalad movement of PCL along airway epithelial surfaces makes this mucus-driven transport an important component of salt and water physiology in the lung in health and disease.     

Airway clearance techniques in the treatment of cystic fibrosis

A one-year-old girl with a giant cell fibroblastoma (GCF) of the skin in the left arm is described. The tumor presented as a small, asymptomatic, subcutaneous mass that enlarged relatively slowly. GCF is a rare mesenchymal tumor occurring predominantly in young children. Its unique histopathological feature can lead to a misdiagnosis as sarcoma very easily. We review briefly the clinical and pathological information of 68 documented cases in the literature and discuss the pathogenesis of this peculiar neoplasm.     

Importance of airway blood flow on particle clearance from the lung

The role of the airway circulation in supporting mucociliary function has been essentially unstudied. We evaluated the airway clearance of inert, insoluble particles in anesthetized ventilated sheep (n = 8), in which bronchial perfusion was controlled, to determine whether airway mucosal blood flow is essential for maintaining surface transport of particles through airways. The bronchial branch of the bronchoesophageal artery was cannulated and perfused with autologous blood at control flow (0.6 ml.min-1.kg-1) or perfusion was stopped. With the sheep in a supine position and after a steady-state 133Xe ventilation scan for designation of lung zones of interest, an inert 99mTc-labeled sulfur colloid aerosol (2.1-microns diameter) was deposited in the lung. The clearance kinetics of the radiolabeled particles were determined from the activity-time data obtained for right and left lung zones. At 60 min postdeposition of aerosol, average airway particle retention for control bronchial blood flow conditions was 57 +/- 7 (SE)% for the right and 53 +/- 8% for the left lung zones. Clearance of particles was significantly impaired when bronchial blood flow was stopped, e.g., right and left lung zones averaged 77 +/- 6 and 76 +/- 7% at 60 min, respectively (P < 0.05). These data demonstrate a significant influence of the bronchial circulation on mucociliary transport of insoluble particles. Potential mechanisms that may account for these results include the importance of the bronchial circulation for nutrient flow, maintenance of airway wall temperature and humidity, and release of mediators and sequelae associated with tissue ischemia.     

Current techniques in heart surgery

Significant advances in open heart surgery during the last two decades were achieved in the field of the extracorporal circulation and the preservation of the myocardium. In the last few years, new therapeutical tools were introduced to treat patients with coronary artery disease. The transmyocardial laser revascularization (TMR) technique was introduced for clinical investigation 1990. Despite limited experience with this device in selected patients, some conclusions after a short follow-up period are available. Patients treated with TMR have significantly less anginal pain and need fewer hospitalisations. With PET follow-up studies, a better subendocardial perfusion at the expense of the subepicardial perfusion was demonstrated. On the other hand, there was no substantial increase found in terms of ejection fraction in treated patients. Minimally invasive procedures have also gained acceptance during the last few years, especially the minimally invasive coronary artery bypass procedures (MIDCAB). Introduced initially to treat solitary stenoses of the LAD without cardiopulmonary bypass, this procedure is actually often used in conjunction with PTCA for three-vessel disease in selected patients. Due to the different methods used and summarized under the term of MIDCAB, definite conclusions about the advantages of this method are difficult to formulate. There is a trend to reduced patency rates of the IMA bypasses in MIDCAB procedures compared to the conventional technique due to the difficulty with limited access.     

Upper airway assessment: radiographic and other imaging techniques

Upper airway imaging is a powerful technique to study the mechanisms underlying the pathogenesis and biomechanics of sleep apnea and the mechanisms underlying the efficacy of therapeutic interventions in patients with sleep disordered breathing. The primary upper airway imaging modalities include nasopharyngoscopy, cephalometrics, CT scanning, and MR imaging. Imaging studies using these modalities have provided important insights into the static and dynamic structure and function of the upper airway and surrounding soft-tissue structures during wakefulness and sleep. Such imaging studies have highlighted the importance of the lateral pharyngeal walls in mediating upper airway caliber. These imaging modalities have also been used to study the effect of respiration, weight loss, mandibular repositioning devices, and upper airway surgery on the upper airway. Three-dimensional reconstruction of the airway and surrounding soft-tissue structures can be performed with MR imaging and CT scanning. Clinical indications for upper airway imaging are evolving such that imaging studies should be considered in patients with sleep apnea who are being treated with dental appliances or upper airway surgery.     

Reproducibility of simplified techniques for the measurement of 51Cr-EDTA clearance

The aim of this study was to assess the reproducibility of a number of simplified clearance methods using chromium-51 ethylenediamine tetraacetic acid (51Cr-EDTA) and to compare these with the multiple blood sample technique. Twenty-four healthy volunteers were enrolled into the study. The test was performed twice, 1 week apart and under similar physiological conditions. After intravenous injection of the tracer, 13 blood samples were taken between 5 and 240 min. The reference clearance was calculated after adapting a bi-exponential fit on the whole plasma disappearance curve. Simplified methods included the slope intercept method using different combinations of blood samples (2 and 4 h; 2, 3 and 4 h; 1.5, 2, 3 and 4 h; 1.5, 2 and 3 h) and several single clearance methods (Constable 3 h; Groth 3 h; Groth 4 h). The standard deviation of the differences between the first and second measurements were similar for all methods, confirming the comparable reproducibility of these methods.     

Regional clearance of solute from peripheral airway epithelia: recovery after sublobar exposure to ozone

The influence of local exposure to ozone (O3) on respiratory epithelial permeability of sublobar lung segments was studied by using aerosolized 99mTc-diethylenetriamine pentaacetic acid (DTPA; mol wt, 492). Two bronchoscopes were inserted through an endotracheal tube in anesthetized, mechanically ventilated, mixed breed dogs and were wedged into sublobar bronchi located in the right and left lower lobes, respectively. Segments were ventilated via the bronchoscope with 5% CO2 in air delivered at 200 ml/min, and an aerosol of 99mTc-DTPA was generated and delivered through the scope and into the sublobar segment over a 30-s period. Clearance of 99mTc-DTPA was measured simultaneously from right and left lower lung segments at baseline and 1, 7, and 14 days after a 6-h sublobar exposure to filtered air or 400 parts per billion O3. O3 treatment significantly decreased the clearance halftime (t50) of 99mTc-DTPA by 50% from the baseline mean of 32.3 to 16.0 min at 1 day postexposure. After 7 days of recovery, t50 was still reduced by 28. 8%; however, by 14 days postexposure, clearance of 99mTc-DTPA had recovered, and the t50 had a mean value of 30.0 min. 99mTc-DTPA clearance was not altered by exposure to filtered air, and t50 values were comparable to baseline at 1, 7, and 14 days postexposure. These results reveal that a single local exposure to O3 increases transepithelial clearance, but only for epithelia directly exposed to O3, and that 7-14 days of recovery are required before permeability to small-molecular-weight solutes returns to normal.     

Current indications and techniques in evaluating inflammatory disease and neoplasia of the sinonasal cavities

Imaging strategies of the sinonasal cavities have undergone extensive revision over the last 5-year period. The traditional imaging examination of the paranasal sinuses, plain film radiography, does reasonably well in diagnosing maxillary, frontal, and sphenoid sinusitis. However, it less reliable in depicting abnormalities in the ethmoid sinuses, the most common area first affected with inflammatory disease. Compared with sinus computed tomography (CT), plain films prove to be less specific and sensitive in depicting the extent of sinus abnormalities. One series plainly concluded that sinus radiographs were not reliable enough to be an integral part of the clinical decision process. The use of plain radiographs of the sinuses has clearly been reduced by medical cost-containment concerns, replacement by superior techniques, and by clear weaknesses of the modality. Although it is inexpensive and easily accessible, the low sensitivities and inaccuracies of plain film radiography have resulted in the current use of CT and high-field-strength (1.5 Tesla) magnetic resonance imaging (MRI). By using this cross-sectional imaging, we now visualize directly the pathologic conditions within the sinuses, as well as the normal anatomy. We discuss current use of diagnostic imaging in the evaluation of patients with nasosinusoidal complaints (most commonly resulting from acute and chronic inflammatory disease), with complications of sinonasal inflammatory disease, and with suspected/documented neoplasia. In addition to developing an imaging algorithm to provide the information affecting clinical decision making, we detail the specific imaging techniques necessary accurately to obtain that information. We also review the specific concerns about imaging patients in the intensive care unit and touch on several emerging imaging techniques. The imaging workup in pediatric patients and patients with congenital anomalies is beyond the scope of this review.     

Positive pressure ventilation with the laryngeal mask airway in non-paralysed patients: comparison of sevoflurane and propofol maintenance techniques

Photofrin photodynamic therapy (PDT) has recently received FDA approval for the palliative treatment of totally and partially obstructing esophageal malignancies. However, there is a need for new PDT photosensitizers because Photofrin has a number of undesirable features. The purpose of this study was to evaluate the efficacy of four amine-bearing silicon phthalocyanines--Pc4, Pc10, Pc12 and Pc18--as potential PDT photosensitizers. Equimolar concentrations of these Pc were found to be highly effective at causing the regression of RIF-1 tumors transplanted to C3H/HeN mice. The amount of Pc4 necessary to cause an equivalent amount of tumor regression in this model system was substantially less than the amount of Photofrin. The cutaneous phototoxicity of the silicon Pc photosensitizer was assessed by the utilization of the murine ear-swelling model. When C3H mice were exposed to 167 J/cm2 of polychromatic visible light from a UVB-filtered solar simulator, which emitted UV radiation and visible light above 320 nm, the Pc produced little, if any, cutaneous photosensitivity. These results indicate that Pc4, Pc10, Pc12 and Pc18 are at least as effective as Photofrin in PDT protocols, while at the same time addressing many of the drawbacks of Photofrin.     

含铁尘泥回收及利用技术现状及发展方向

在对含铁尘泥的来源、性质和分类进行界定的基础上,系统地介绍了国内外含铁尘泥处置、回收及利用技术现状,指出了含铁尘泥回收与利用的发展方向,可为钢铁工业含铁尘泥的综合利用提供参考。     

Renal clearance of ifosfamide

Nephrotoxicity is an important clinical side effect of the chemotherapeutic agent ifosfamide. This medication is activated by the hepatic cytochrome P450 system with potentially toxic metabolites produced through both ring hydroxylation and chloroethyl side chain oxidation pathways. Using an isolated perfused rat kidney preparation, we examined the possibility that renal metabolism of ifosfamide also occurs. Renal function before and after addition of ifosfamide to perfusate was not significantly different. After addition of ifosfamike to the perfusate, the metabolites N2-dechloroethylifosfamide, N3-dechloroethylifosfamide, and isophasphoramide mustard were recovered from urine and renal venous effluent. These results provide the first demonstration of ifosfamide metabolism by the kidney and suggest the possibility that intrarenal metabolism may contribute to nephrotoxicity.     

P-Selectin and platelet clearance

P-selectin is an adhesion receptor for leukocytes expressed by activated platelets and endothelial cells. To assess a possible role of P-selectin in platelet clearance, we adapted an in vivo biotinylation technique in mice. Wild-type and P-selectin-deficient mice were infused with N-hydroxysuccinimido biotin. The survival of biotinylated platelets was followed by flow cytometry after labeling with fluorescent streptavidin. Both wild-type and P-selectin-deficient platelets presented identical life spans of about 4.7 days, suggesting that P-selectin does not play a role in platelet turnover. When biotinylated platelets were isolated, activated with thrombin, and reinjected into mice, the rate of platelet clearance was unchanged. In contrast, storage of platelets at 4 degreesC caused a significant reduction in their life span in vivo but again no significant differences were observed between the two genotypes. The infused thrombin-activated platelets rapidly lost their surface P-selectin in circulation, and this loss was accompanied by the simultaneous appearance of a 100-kD P-selectin fragment in the plasma. This observation suggests that the platelet membrane P-selectin was shed by cleavage. In conclusion, this study shows that P-selectin, despite its binding to leukocytes, does not mediate platelet clearance. However, the generation of a soluble form of P-selectin on platelet activation may have biological implications in modulating leukocyte recruitment or thrombus growth.