Long-term effects of physical exercise on working capacity and pulmonary function in cystic fibrosis

Seven patients with cystic fibrosis aged 6 to 20 were enrolled for 30 months in a daily exercise program. After 12 months conventional chest physiotherapy was withdrawn. Patients with low initial Shwachman scores improved as regards maximal working capacity. Spirometric data and volume of trapped gas indicated opening of closed airways. We suggest that physical exercise in general should be the basis of pulmonary therapy in cystic fibrosis. Other forms of physiotherapy are advisable when hard physical exercise is not feasible.     

指示肺通气不均匀性的熵变及其同其他指标的理论比较

熵代表无序的水平，作者使用通气的熵变（ＥＣＶ）指示肺通气的不均匀性，ＥＣＶ定义为当前泡潮气量趋近于零时每摩尔被吸入气体从不均匀通气到均匀通气的熵变的极限。本文从熵的基本公式民地出ＥＣＶ的计算方程。用几个数学模型肺将ＥＣＶ同其他７个洗出指标进行了比较。８个指标中，只有ＥＣＶ仅取决于通气分布，其他７个指标不仅取决于通气分布，还同潮气量和死腔的大小有关。这影响了它们评价肺通气不均匀性的效果，ＥＣＶ的另一     

Healthy lungs tolerate repetitive collapse and reopening during short periods of mechanical ventilation

The possible occurrence of lung damage if alveolar units are allowed to collapse and reopen breath by breath during mechanical ventilation with normal tidal volumes was investigated. Anaesthetised, paralysed, open chest rabbits were subjected to either intrathoracic negative (NEEP; n=6) or positive (PEEP; n=6) end-expiratory pressure during volume controlled mechanical ventilation. Both experimental settings were preceded by a 30 min control period and followed by a 30 min recovery period during which a PEEP of 0.2 kPa was maintained. Pao₂ and pulmonary compliance deteriorated significantly in the NEEP group during the experimental period and compared to ventilation with PEEP. Partial restoration of lung mechanics and blood gases was achieved during the recovery period. After an alveolar recruitment manoeuvre, this recovery was complete. Lung clearance studied by depositing an aerosol of technetium-99m-labelled diethylenetriamine pentaacetate (^99mTc-DTPA) in the alveoli, was significantly faster during ventilation with NEEP compared to the PEEP group ( P =0.0002) as well as the control period ( P = 0.0029). It did not recover completely during the recovery period but remained significantly faster. light microscopic histology was normal in both groups with no evidence of inflammation or epithelial disruption. We conclude that previously healthy rabbit lungs show only a transient disturbance of lung mechanics and blood gases with repetitive collapse and re-expansion. The integrity of the alveolar rnicrostructure is preserved. The disturbance in the alveolo-capillary permeability persists and may indicate surfactant related alveolo-capillary barrier dysfunction.     

Different kinetics of lung clearance of technetium-99m labelled diethylene triamine penta-acetic acid in patients with sarcoidosis and smokers

The rate of clearance from the lungs of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (^99mTc-DTPA) is often increased in interstitial lung disease as well as in smoking. In smokers a bi-exponential clearance course of ⁹⁹mTc-DTPA when measured over 3 h has previously been shown. This study was performed to compare the kinetics of clearance of ^99mTc-DTPA, measured for 3 h, in sarcoid patients and healthy smokers. Forty-one never-smoking patients with sarcoidosis and radiological signs of intrathoracic disease were studied. The results were compared with those of 16 healthy current smokers and of 14 healthy never-smokers reported previously. A mono-exponential clearance equation described the clearance in 22 of the sarcoid patients and all normal never-smokers, but with a shorter average tracer half-life in the patients (P<0.05). In 19 patients and all smokers a bi-exponential equation gave a significantly better curve fit. The rate of clearance of the slow component was higher in patients with sarcoidosis than in smokers (P< 0.05). The fraction of the tracer cleared by the fast clearance component was smaller in patients with sarcoidosis than in smokers (P<0.01). Differences in kinetics of clearance of ^99mTc-DTPA in sarcoidosis and smoking could thus be demonstrated, suggesting that the abnormal clearance is caused by diverging pathophysiological mechanisms.     

A nonlinear model of the arterial vessels within a limb segment

The relationship between the arterial blood pressure and the volume of the arteries within a segment of an extremity is nonlinear. The present paper shows how the flow and volume pulsations of the arteries within a limb segment can be simulated taking this property into account. An electrical model was constructed comprising one resistor and two voltage dependent ‘capacitors’, the latter corresponding to the pressure dependent elasticity, or compliance, of the arteries. Adequate simulations were obtained over a wide pressure range, which is impossible with linear models. The nonlinear, i.e. pressure dependent, relationship between the volume and pressure of arteries, observed under static conditions, must also be taken into consideration when studying pulsatile events with models whether mathematical or physical.     

Pulmonary clearance of inhaled [99Tcm]DTPA: effects of ventilation pattern

While a rise in lung volume is known to increase the pulmonary clearance of technetium-99m-labelled dietylene triamine pentaacetate ([99Tcm]DTPA), little interest has been focused on the effects of changes in ventilation frequency, tidal volume and airway pressure. We studied adult, anaesthetized and intubated rabbits during three ventilation patterns (VP) using pressure controlled ventilation (ServoVentilator 900C). VP was either deep slow (f = 20 min-1, tidal volume (VT) = 30 +/- 4 ml kg-1 and positive end-expiratory pressure (PEEP) = 0.2 kPa [VP 20/0.2, n = 8]) or rapid shallow (f = 80 min-1, VT = 11 +/- 2 ml kg-1 and PEEP = 0.2 or 0.4 kPa [VP 80/0.2, n = 6 and VP 80/0.4, n = 6]). The mean airway pressure was similar at VP 20/0.2 and VP 80/0.4. During administration of [99Tcm]DTPA aerosol all animals were ventilated under the same conditions (f = 40 min-1 and PEEP = 0.2 kPa). The pulmonary clearance rate expressed as the half-life time (T1/2) of [99Tcm]DTPA was at VP 80/0.2 = 113 +/- 31 min, at VP 80/0.4 = 70 +/- 24 min (P less than 0.01 compared to VP 80/0.2) and at VP 20/0.2 = 36 +/- 18 min (P less than 0.001 compared to VP 80/0.2 and P less than 0.01 compared to VP 80/0.4). We conclude that the pulmonary clearance of [99Tcm]DTPA increases (1) during rapid shallow ventilation when PEEP is increased from 0.2 to 0.4 kPa; (2) during deep slow ventilation relative to rapid shallow ventilation even when the mean airway pressure is similar.     

Characterization of genomically amplified segments using PCR: optimizing relative-PCR for reliable and simple gene expression and gene copy analyses

Gene amplification is one of the mechanisms for oncogene activation in solid tumors. The size of the amplified regions may vary considerably among individual tumors, and more than one gene may be affected within the same amplicon. The main objective in analyzing genomic amplifications has therefore been to map the shortest region involved and to identify genes with increased expression as a result of the increased gene copy number. To facilitate such an analysis, we have developed simple polymerase chain reaction (PCR) procedures using the internal standards beta-actin (ACTB) and L1Hs for gene expression and gene copy number analyses, respectively. We used cDNA derived from pancreatic carcinoma cell lines, and genomic DNA extracted from the same cell lines, as templates in the gene expression and in the gene copy number analyses, respectively. To determine the optimal number of PCR cycles, dilution series of the templates were made. Furthermore, competing primers were used to adjust for differences in target sequence levels. We show that by these simple means it is possible to determine optimal conditions for expression analyses. In addition, the procedure was adapted for the analysis of gene copy number changes at the genomic level using L1Hs as the internal standard. This PCR method makes it possible to produce detailed gene copy number profiles of amplified genomic regions.     

Comparative breast tumor imaging and comparative in vitro metabolism of 16alpha-[18F]fluoroestradiol-17beta and 16beta-[18F]fluoromoxestrol in isolated hepatocytes

16beta-[18F]Fluoromoxestrol ([18]betaFMOX) is an analog of 16alpha-[18F]fluoroestradiol-17beta ([18F]FES), a radiopharmaceutical known to be an effective positron emission tomography (PET) imaging agent for estrogen receptor-positive (ER+) human breast tumors. Based on comparisons of target tissue uptake efficiency and selectivity in a rat model, [18F]betaFMOX was predicted to be as effective an imaging agent as [18F]FES. However, in a preliminary PET imaging study with [18F]FMOX of 12 patients, 3 of whom had ER+ breast cancer, no tumor localization of [18F]betaFMOX was observed. In search for an explanation for the unsuccessful [18F]betaFMOX clinical trial, we have examined the rate of metabolism of [18F]FMOX and [18F]FES in isolated rat, baboon, and human hepatocytes. We have also studied the effect of the serum protein sex hormone-binding globulin (SHBG), which binds [18F]FES better than [18F]betaFMOX, on these rates of metabolism. Immature rat hepatocytes were found to metabolize [18F]FES 31 times faster than [18F]betaFMOX, whereas mature rat cells metabolized [18F]FES only 3 times faster, and baboon and human hepatocytes only 2 times faster than [18F]betaFMOX. In the presence of SHBG, the metabolic consumption rate for [18F]FES in mature rat hepatocytes decreased by 26%. Thus, the very favorable target tissue uptake characteristics of [18F]betaFMOX determined in the rat probably result from its comparative resistance to metabolism (vis-a-vis [18F]FES) in this species, an advantage that is strongly reflected in comparative metabolism rates in rat hepatocytes. In the baboon and human, [18F]FES is extensively protein bound and protected from metabolism, an effect that may be reflected to a degree as a decrease in the rate of metabolism of this compound in baboon and human hepatocytes relative to [18F]betaFMOX. Thus in primates, SHBG may potentiate the ER-mediated uptake of [18F]FES in ER+ tumors by selectively protecting this ligand from metabolism and ensuring its delivery to receptor-containing cells. In addition to current screening methods for 18F-estrogens that involve evaluating in vivo ER-mediated uptake in the immature female rat, studies comparing the metabolism of the new receptor ligands in isolated hepatocytes, especially those from primates or humans, may assist in predicting the potential of these ligands for human PET imaging.