Elastic pressure-volume curves indicate derecruitment after a single deep expiration in anaesthetised and muscle-relaxed healthy man

BACKGROUND: In acute respiratory distress syndrome, lung volume is lost immediately after positive end-expiratory pressure (PEEP) is removed and is not immediately regained when PEEP is restored to its original value. The aim of this study was to investigate whether the same phenomenon also occurs in cardiopulmonary healthy individuals during anaesthesia and muscle relaxation. METHODS: In 13 anaesthetised and muscle-relaxed patients, inspiratory elastic pressure-volume (Pel-V) curves were, after lung recruitment, obtained from zero end-expiratory airway pressure (ZEEP) and from a PEEP of 5 cmH2O. The curves were aligned on a common volume axis. Differences in lung volumes and compliance (Crs) were calculated at the different airway pressures. RESULTS: At comparable pressures the ZEEP curve showed significantly lower volumes up to an airway pressure of 25 cmH2O. Maximum Crs was similar on the curves obtained from ZEEP and PEEP. However, the lower segments of the curve recorded from PEEP showed lower Crs compared to the curve recorded from ZEEP. CONCLUSION: During anaesthesia and muscle paralysis, the Pel-V relations change immediately when 5 cmH2O of PEEP is removed. This phenomenon is probably mainly caused by closure of small airways and only in a minor part, if any, by formation of atelectasis. This study indicates that under these conditions lung volume might easily be normalised by a large breath producing an airway pressure of 20 cmH2O.     

Computer-aided ventilator resetting is feasible on the basis of a physiological profile

BACKGROUND: Ventilator resetting is frequently needed to adjust tidal volume, pressure and gas exchange. The system comprising lungs and ventilator is so complex that a trial and error strategy is often applied. Comprehensive characterization of lung physiology is feasible by monitoring. The hypothesis that the effect of ventilator resetting could be predicted by computer simulation based on a physiological profile was tested in healthy pigs. METHODS: Flow, pressure and CO2 signals were recorded in 7 ventilated pigs. Elastic recoil pressure was measured at postinspiratory and post-expiratory pauses. Inspiratory and expiratory resistance as a function of volume and compliance were calculated. CO2 elimination per breath was expressed as a function of tidal volume. Calculating pressure and flow moment by moment simulated the effect of ventilator action, when respiratory rate was varied between 10 and 30 min(-1) and minute volume was changed so as to maintain PaCO2. Predicted values of peak airway pressure, plateau pressure, and CO2 elimination were compared to values measured after resetting. RESULTS: With 95% confidence, predicted pressures and CO2 elimination deviated from measured values with < 1 cm H2O and < 6%, respectively. CONCLUSION: It is feasible to predict effects of ventilator resetting on the basis of a physiological profile at least in health.     

Measurement of ventilation and respiratory mechanics during continuous positive airway pressure (CPAP) treatment in infants

A new method has been evaluated for measuring ventilation and lung mechanics in spontaneously breathing infants by means of a face chamber. Airway flow is measured with a pneumotachograph inserted between the face chamber and a stable pressure source. Oesophageal pressure is measured via a water-filled oesophageal catheter. The method is suitable for use in conjunction with continuous positive airway pressure (CPAP) treatment in neonatal intensive care. A flat frequency response curve up to 15 Hz for the two measuring systems (i.e., airway flow and oesophageal pressure), and a time shift between the two respective signals of less than 2 msec are prerequisites for correct evaluation of respiratory mechanics. In preterm infants with chest distortion, the inhomogeneity of pleural pressure affects the significance of resistance and compliance values, as calculated from oesophageal pressure. Supra-diaphragmatic pressure variations reflect the resistive and elastic load on the diaphragm exerted by the lungs and thorax. Thus, oesophageal pressure is still useful in studies of respiratory mechanics in preterm infants.     

Potentially of early chest roentgen examination in ventilator treated newborn infants to predict future lung function and disease

The potentially of early chest X-ray to predict the risk of lung function abnormalities was studied prospectively in 40 preterm ventilator treated infants in a 8–10-year follow-up investigation. According to the findings at chest X-ray 3 to 10 days after completed ventilator treatment the infants were divided into 3 groups considered to represent increasing risk and severity of lung damage: 1) normal findings, 2) interstitial parenchymal abnormalities exclusively or 3) in combination with local or general hyperinflation. Lung function tests and chest x-ray were performed at the age of 8 to 10 years. A correlation was found between the findings at the early chest roentgen examination and the risk of abnormal lung function at the follow-up. Occurrence of focal or general hyperinflation or both were associated with a greater risk of airway obstruction. Infants with only interstitial abnormalities were, however, at a higher risk than those with normal chest examination to develop general hyperinflation and increased air way obstruction.     

Selective deposition of inhaled aerosols to mechanically ventilated rabbits.

We have studied selective deposition of tracer aerosols to specific sites in airways and peripheral regions of the rabbit lung by varying droplet size and breathing pattern. The different breathing patterns were controlled by a Servo Ventilator 900C and different droplet sizes (polydisperse) were generated by an air jet nebulizer (MA2) using two types of impactor vessels (MMD 2.3 and 4.1 microns). Three tracer aerosols were evaluated; Evans blue dye, 99mTc-DTPA and monodisperse fluorescent polylatex spheres (PLS). When we combined large droplets with "rapid-shallow" breathing (central deposition mode, CDM), 30% of the aerosol was deposited in the central airways. When small droplets were combined with "deep-slow" breathing (peripheral deposition mode, PDM) 60% was deposited in the peripheral part of the lung. The different detection techniques showed similar results but gave complementary information. Since detection of the radiolabelled aerosol was more sensitive than the other methods, less aerosol could be given allowing a more precise evaluation of the deposition, both from the macro autoradiographic images as well as from the well counter measurements. In order to investigate how far into the lung periphery the aerosol could be detected, we used PSL microspheres. PLS could be detected in the alveolar region by a fluorescent light microscope. However, a complete selectivity can not be obtained by aerosol delivery. The different technique used to reach selective deposition, showed that it is only possible to deposit the aerosol either more to the central or more to the peripheral parts of the respiratory tract in small subjects.     

Radiochemical synthesis and tissue distribution of Tc-99m-labeled 7alpha-substituted estradiol complexes

The diagnosis and staging of breast cancer could be improved by the development of radiopharmaceutical imaging agents that provide a noninvasive determination of the estrogen receptor (ER) status of tumor cells. Agents labeled with (99m)Tc would be especially valuable in this regard. In attempting to achieve this goal, we synthesized four (99m)Tc-labeled 7alpha-substituted estradiol complexes. One complex utilizes the "3+1" mixed ligand design to introduce the Tc metal, whereas the other three took advantage of the cyclopentadienyltricarbonylmetal (CpTM) design. The Tc moieties were attached to the 7alpha position of estradiol with a hexyl tether, a monoether tether, or a polyether tether. The corresponding rhenium compounds have binding affinities for the ER of 20-45% compared with estradiol. Radiochemical yields of the (99m)Tc-labeled compounds ranged from approximately 15% for the CpT-Tc complexes to 95% for the 3 + 1 inorganic complex. Tissue distribution studies in immature female rats showed low nonreceptor-mediated uptake in the target organs and high uptake in nontarget organs such as the liver and fat. These complexes represent the first time that estradiol has been labeled at the 7alpha position with (99m)Tc and provide a further refinement of our understanding of ligand structure-binding affinity correlations for the ER.     

Correlation between clinicopathological features and karyotype in 100 cartilaginous and chordoid tumours. A report from the Chromosomes and Morphology (CHAMP) Collaborative Study Group.

The evaluation of chondroid lesions requires full integration of clinical, radiographic, and pathological data; tumour typing is often a challenge for the diagnostic pathologist. Although a variety of chromosomal abnormalities have been documented in chondroid lesions, the potential usefulness of cytogenetic analysis remains unclear. This study has critically reviewed and analysed 117 karyotyped samples from 100 patients with cartilaginous and chordoid tumours. Cases were selected based on successful chromosomal analysis and adequacy of clinical, radiographic, and pathological information. To ensure objective evaluation, the cytogenetic results were correlated in a double-blind setting with consensus diagnoses independently determined on each case, after complete review of the histological, radiographic, and clinical findings. Karyotypic aberrations were identified in 41/92 cartilaginous tumours (5/11 osteochondromas, 2/3 chondromyxoid fibromas, 0/4 chondroblastomas, 11/29 chondromas, 0/3 chondroid tumours of undetermined malignant potential, 22/40 chondrosarcomas and 1/2 miscellaneous cartilaginous lesions) and 5/8 chordomas. Complex karyotypic changes were a feature of malignant tumours (chondrosarcoma and chordoma) and of chondrosarcoma among cartilaginous tumours, where they correlated with high tumour grade. Among primary well-differentiated cartilaginous lesions of bone, the finding of an abnormal karyotype was consistently associated with a grade 1 chondrosarcoma diagnosis. Among karyotypically abnormal cartilaginous tumours, loss of distal 8q was associated with osteochondroma, +5 with synovial chondroma/chondromatosis and parosteal or soft tissue chondroma, alterations of chromosome arm 6q with chondromyxoid fibroma, +7 with bone chondrosarcoma, and 17p1 alterations with grade 3 chondrosarcoma. Alterations involving 12q13 characterized synovial chondroma/chondromatosis in the chondroma group and myxoid chondrosarcoma of bone in the chondrosarcoma group. In conclusion, cytogenetic abnormalities in chondroid lesions are common and are not randomly distributed. They are associated with malignancy/tumour grade as well as with specific diagnoses in many cases, and can therefore be of potential value for tumour typing.     

Detailed genomic mapping and expression analyses of 12p amplifications in pancreatic carcinomas reveal a 3.5-Mb target region for amplification

Previous cytogenetic and comparative genomic hybridization (CGH) analyses have shown that the gain of chromosome arm 12p is frequent in pancreatic carcinomas. We investigated 15 pancreatic carcinoma cell lines using CGH, fluorescence in situ hybridization (FISH), and semiquantitative polymerase chain reaction (PCR) to characterize 12p amplifications in detail. The CGH analysis revealed gains of 12p in four of the cell lines and local amplification within 12p11-12 in six cell lines. By FISH analysis, using precisely mapped YAC clones, the commonly amplified region was found to be approximately 5 Mb. The amplified segment extended from YAC 753f12, covering the KRAS2 locus, to YAC 891f1, close to the centromere. A semiquantitative PCR methodology was used to estimate genomic copy numbers of 14 precisely mapped expressed sequence tags (ESTs) and sequence-tagged sites, located within this interval. The level of amplification ranged from two- to 12-fold. The produced gene copy profiles revealed a 3.5-Mb segment with various local amplifications. This region includes KRAS2 and ranges from D12S1617 to sts-N38796. Two of the cell lines (primary and metastatic tumor from the same patient) showed amplification peaks within the distal region of this segment, two had peaks within the proximal region, one showed subpeaks in both regions, and one displayed amplification of the entire region. Chromosome segment-specific cDNA array analysis of 29 expressed sequences within the whole interval between D12S1617 and sts-N38796 indicated overexpression of four ESTs, two corresponding to DEC2 and PPFIBP1, and two to ESTs with unknown function. Expression analysis of these and of KRAS2 showed specific overexpression in the six cell lines with local 12p amplifications. These findings indicate two target regions within the 3.5-Mb segment in 12p11-12, one proximal including PPFIBP1, and one distal including KRAS2.     

Stress fractures of the pelvis in female navy recruits: an analysis of possible mechanisms of injury

The purpose of our study was to investigate possible risk factors and mechanisms for the development of pelvic stress fractures in female Navy recruits. We used a case-control retrospective study of female Navy recruits undergoing basic military training. We compared anthropometric and activity data between recruits with pelvic stress fractures (N = 25) and female recruits who completed training without injury (N = 61). Recruits developing pelvic stress fractures were significantly (p < 0.05) shorter and lighter and were more frequently Asian or Hispanic than recruits without stress fractures. In addition, recruits with pelvic stress fractures reported marching in the back of their training division, were road guards, and felt that their stride was too long during training activities more often than recruits without injury. Self-reported fitness, activities before recruit training, or a history of amenorrhea was not found to be associated with the development of a pelvic stress fracture in our population.