Arginase as a useful factor for the diagnosis of colorectal cancer liver metastases.

The present work is a continuation of studies on arginase as a marker in the diagnosis of colorectal cancer liver metastases (CRCLM). The purpose of the study was the evaluation of the arginase test in comparison with other colorectal cancer tests such as CEA, CA 19-9 and biochemical markers of liver function such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The studies were conducted on blood serum from 85 patients with CRCLM obtained one to two days before tumor resection. The control group comprised 140 healthy blood donors and 81 patients with various non-malignant gastrointestinal diseases. Raised arginase activity was observed in serum of 85% of CRCLM patients, whereas elevated levels of CEA and CA 19-9 were found in 63% and 42% of patients, respectively. The combination of CEA or CA 19-9 with the arginase assay improved their sensitivity, but the sensitivity of the combined parameters was not higher than that of the arginase test itself. AST and ALT activities were increased in about 30% of CRCLM patients. The specificity of the arginase test calculated for 221 control subjects was 76%. It can thus be concluded that the determination of serum arginase activity can be helpful in the diagnosis of patients with colorectal cancer liver metastases.

The effect of serotonin, its precursors and metabolites on brain glutathione-S-transferase.

The isoelectric point and substrate specificity of the main isoform of glutathione-S-transferase (GST, EC 2.5.1.18) isolated from brain stem, hippocampus and parietal cortex of pig brain were determined. The effect of serotonin, its precursors (Try, 5-HTry), physiologically active derivative (melatonin) and final metabolite (5-HIAA) on the activity of this form was examined. Investigation indicated that serotonin did not affect the activity of GST in all studied regions of brain. The inhibitory effect of Try was stronger than that of 5-HTry, but weaker than the one expressed by melatonin and especially by 5-HIAA. Studies on the type of inhibition showed that Try, melatonin and 5-HIAA can compete for the active site with the electrophilic substrate but not with glutathione. Therefore precursors and endogenous derivatives of serotonin but not serotonin itself may affect the detoxification function of brain glutathione-S-transferase and increase the exposure of brain to toxic electrophiles.

Arginase isoforms in human colorectal cancer.

Arginase (EC 3.5.3.1) activity was determined in 54 colorectal tissues obtained from patients with primary colorectal adenocarcinoma as well as in serum of 45 patients and 65 healthy individuals. In patients, the preoperative values of the mean serum arginase activity and the activity in colorectal tumors were much higher than in serum of healthy subjects and control tissues. Two isoforms of arginase, anionic and cationic, were identified in colorectal tissues (normal and cancerogenous), and only one, the cationic form, in serum. These arginases were different from the main human liver cationic arginase (pI 9.3). The anionic colorectal arginase was identical with the human liver anionic isoform (pI 7.7), and the cationic arginase from colorectal tissues and blood serum with the human kidney cationic enzyme (pI 8.9). The total activity and the level of protein of the cationic arginase in colorectal cancer was higher than in control tissue, and it was also higher in serum of patients with colorectal cancer than in healthy subjects. Thus, it can be concluded that the increased arginase activity in blood serum and colorectal cancer in studied patients was due to the raised level of the cationic arginase and this isoform seems to be a discriminating parameter for assessing the presence of colorectal cancer.

[Tricyclic antidepressants as inhibitors of brain glutathione-S-transferase]. / Trójpierscieniowe leki przeciwdepresyjne jako inhibitory mózgowej transferazy glutationowej.

Tricyclic antidepressants, amitriptyline, doxepin--derivatives of cycloheptadiene as well as imipramine and clomipramine, derivatives of dibenzazepine inhibit the activity of glutathione-S-transferase pi isolated from different regions of human brain (parietal cortex, frontal cortex, brain stem). The inhibitory effect of studied drugs depends more on their chemical structure than on brain localization of the enzyme. All tricyclics bind nonspecifically to the effector site of glutathione-S-transferase (GST). The obtained results indicate that the inhibitory effect of tricyclic antidepressants on brain GST may decrease the efficiency of the enzymatic barrier, which protects brain against toxic electrophiles, and contribute in their adverse effects. On the other hand, brain GST may decrease the therapeutic effects of tricyclic antidepressants by binding them as ligands.

Correlation of changes in quality of life after lung volume reduction surgery with changes in lung function, exercise, and gas exchange.

STUDY OBJECTIVES: To evaluate correlations between improvement in quality of life (QOL) in patients with severe COPD before and after they undergo lung volume reduction surgery (LVRS) with changes in pulmonary function tests, gas exchange, exercise performance, and alterations in medical management. DESIGN: Case-series analysis. SETTING: University hospital. PATIENTS: Forty-two patients (mean [+/- SD] age, 56+/-8 years; 53% women) with severe airflow obstruction (FEV(1), 0.62+/-0.2 L), and moderate to severe hyperinflation (total lung capacity [TLC], 6.9+/-1.7 L). INTERVENTION AND MEASUREMENTS: All patients underwent bilateral LVRS via median sternotomy. Measurements of lung function, symptom-limited cardiopulmonary exercise testing, the total distance the patient was able to walk in 6 min in a corridor, and sickness impact profile (SIP) scores were made before and 3 months after LVRS. SIP scores are inversely proportional to the level of function and QOL. RESULTS: Compared to baseline, FEV(1) increased (0.87+/-0.3 vs. 0.62+/-0.2 L, respectively; p<0.01) while residual volume significantly decreased (3.2+/-1.8 vs. 6.3+/-1.2 L, respectively; p<0.004) at 3 months post-LVRS. On cardiopulmonary exercise testing, values increased from baseline to post-LVRS for total exercise time (9.0+/-2.2 vs. 6.0+/-1.5 min, respectively; p = 0.045), maximum oxygen uptake (VO(2)) (16+/-3 vs. 11+/-2 mL/kg/min, respectively; p = 0.01), and maximum minute ventilation (VE) (33+/-9 vs. 28+/-5 L/min, respectively; p = 0.03). The percentage change in the oxygen cost of breathing (VO2/VE ratio) from low to high workloads during exercise was significantly lower after LVRS (p = 0.002). There was no significant change in oxygenation after LVRS (PaO(2)/fraction of inspired oxygen, 331+/-27 vs. 337+/-39, respectively; p = 0.76), but PaCO(2) tended to be lower (41+/-9 vs. 48+/-6 mm Hg, respectively; p = 0.07). Overall SIP scores were significantly lower after LVRS than before (8+/-4 vs. 15+/-2, respectively; p = 0.002). Changes in SIP scores correlated with the change in VO2/VE ratio from low to high workloads, with patients having the smallest changes in VO2/VE ratio having the smallest changes in SIP scores after LVRS (r = 0.6; p = 0.01). Improved or lower SIP scores also tended to correlate with a reduction in residual volume/TLC ratio (r = 0.45; p = 0.09), and there was a linear correlation with a statistically significant Pearson r value with decreased steroid requirements (r = 0.7; p = 0.001). Moreover, changes in psychological SIP subscore tended to correlate with diminished oxygen requirements post-LVRS (r = 0.45; p = 0.09). However, there was no significant correlation between changes in SIP scores and routine measurements of lung function, exercise performance, or gas exchange. CONCLUSION: There is an association between an improvement in QOL and reduced hyperinflation after LVRS. Reduced hyperinflation may lead to more efficient work of breathing during exercise and, therefore, to an increased ability to perform daily activities. Changes in QOL scores correlate best with behaviorally based variables that directly affect the patient's well-being, such as systemic steroid administration.

Glutathione conjugation in male reproductive system: studies on glutathione-S-transferase of bull and boar epididymis.

Male reproductive organs are extremely sensitive to the negative influence of toxic environmental factors as well as drugs, and until now not many attempts have been made at studying the detoxication enzymes and the relationship between the activity of those enzymes and spermatozoa fertility. In the present work we studied cytosolic glutathione-S-transferases (GST, EC 2.5.1.18) from different parts (head, corpus and tail) of bull and boar epididymis. We isolated two molecular forms of GST from each part of epididymis, characterized their biochemical properties and examined the mechanism of the catalyzed reaction. On the basis of their substrate specificity and isoelectric point, the isoforms were found to belong to the near neutral GST class mi. All examined GST forms exhibited higher affinity towards GSH than towards 1-chloro-2,4-dinitrobenzene (CDNB) and bull epididymis GST forms showed biphasic Lineweaver-Burk double reciprocal curves in the presence of GSH as a variable substrate. Boar epididymis anionic GST had the -SH groups both in the GSH and the CDNB binding place, whereas the cationic GST form--arginine residues in the CDNB binding place. Bull epididymis GST forms contained neither thiol nor arginine residues essential for catalytic activity.

Prospective randomized trial comparing bilateral lung volume reduction surgery to pulmonary rehabilitation in severe chronic obstructive pulmonary disease.

Several uncontrolled studies report improvement in lung function, gas exchange, and exercise capacity after bilateral lung volume reduction surgery (LVRS). We recruited 200 patients with severe chronic obstructive pulmonary disease (COPD) for a prospective randomized trial of pulmonary rehabilitation versus bilateral LVRS with stapling resection of 20 to 40% of each lung. Pulmonary function tests, gas exchange, 6-min walk distance, and symptom-limited maximal exercise testing were done in all patients at baseline and after 8 wk of rehabilitation. Patients were then randomized to either 3 additional months of rehabilitation or LVRS. Thirty-seven patients met study criteria and were enrolled into the trial. Eighteen patients were in the medical arm; 15 of 18 patients completed 3 mo of additional pulmonary rehabilitation. Thirty-two patients underwent LVRS (19 in the surgical arm, 13 crossover from the medical arm). After 8 wk of pulmonary rehabilitation, pulmonary function tests remained unchanged compared with baseline data. However, there was a trend toward a higher 6-min walk distance (285 +/- 96 versus 269 +/- 91 m, p = 0.14) and total exercise time on maximal exercise test was significantly longer compared with baseline values (7.4 +/- 2.1 versus 5.8 +/- 1.7 min, p < 0.001). In 15 patients who completed 3 mo of additional rehabilitation, there was a trend to a higher maximal oxygen consumption (V O(2)max) (13.3 +/- 3.0 versus 12.6 +/- 3.3, p < 0.08). In contrast, at 3 mo post-LVRS, FVC (2.79 +/- 0.59 versus 2.36 +/- 0.55 L, p < 0.001) and FEV(1) (0.85 +/- 0.3 versus 0.65 +/- 0.16 L, p < 0.005) increased whereas TLC (6.53 +/- 1.3 versus 7.65 +/- 2.1 L, p < 0.001) and residual volume (RV) (3.7 +/- 1.2 versus 4.9 +/- 1.1 L, p < 0.001) decreased when compared with 8 wk postrehabilitation data. In addition, Pa(CO(2)) decreased significantly 3 mo post-LVRS compared with 8 wk postrehabilitation. Six-minute walk distance (6MWD), total exercise time, and V O(2)max were higher after LVRS but did not reach statistical significance. However, when 13 patients who crossed over from the medical to the surgical arm were included in the analysis, the increases in 6MWD (337 +/- 99 versus 282 +/- 100 m, p < 0.001) and V O(2)max (13.8 +/- 4 versus 12.0 +/- 3 ml/kg/min, p < 0.01) 3 mo post-LVRS were highly significant when compared with postrehabilitation data. The Sickness Impact Profile (SIP), a generalized measure of quality of life (QOL), was significantly improved after 8 wk of rehabilitation and was maintained after 3 mo of additional rehabilitation. A further improvement in QOL was observed 3 mo after LVRS compared with the initial improvement gained after 8 wk of rehabilitation. There were 3 (9.4%) postoperative deaths, and one patient died before surgery (2.7%). We conclude that bilateral LVRS, in addition to pulmonary rehabilitation, improves static lung function, gas exchange, and QOL compared with pulmonary rehabilitation alone. Further studies need to evaluate the risks, benefits, and durability of LVRS over time.

Relationship between resting hypercapnia and physiologic parameters before and after lung volume reduction surgery in severe chronic obstructive pulmonary disease.

Patients with severe chronic obstructive pulmonary disease (COPD) have varying degrees of hypercapnia. Recent studies have demonstrated inconsistent effects of lung volume reduction surgery (LVRS) on PaCO2; however, most series have excluded patients with moderate to severe hypercapnia. In addition, no study has examined the mechanisms responsible for the reduction in PaCO2 post-LVRS. We obtained spirometry, body plethysmography, diffusion capacity, respiratory muscle strength, 6-min walk test, and incremental symptom-limited maximal exercise data in 33 consecutive patients pre- and 3 to 6 mo post-LVRS, and explored the relationship between changes in PaCO2 and changes in the measured physiologic variables. All patients underwent bilateral LVRS via median sternotomy and stapling resection by the same cardiothoracic surgeon. Patients were 57 +/- 8 yr of age with severe COPD, hyperinflation, and air trapping (FEV1, 0.73 +/- 0.2 L; TLC, 7.3 +/- 1.6 L; residual volume [RV], 4.8 +/- 1.4 L), and moderate resting hypercapnia (PaCO2, 44 +/- 7 mm Hg; range, 32 to 56 mm Hg). Post-LVRS, PaCO2 decreased by 4% (PaCO2 pre 44 +/- 7 mm Hg, PaCO2 post 42 +/- 5 mm Hg; p = 0.003). Patients with higher baseline values of PaCO2 had the greatest reduction in PaCO2 post-LVRS (r = -0.61, p < 0.001). Significant correlations existed between reduction in PaCO2 and changes in FEV1 (r = -0.56; p = 0.0007), maximal inspiratory pressure (PImax) (r = -0.46; p = 0.009), diffusing capacity of the lungs for carbon monoxide (DLCO) (r = -0.47; p = 0.008), and RV/TLC (r = 0.41; p = 0. 02). Correlation existed also between reduction in PaCO2 and breathing pattern at maximal exercise: maximal minute ventilation (V Emax) (r = -0.47; p = 0.009), and tidal volume (VT) (r = -0.40; p = 0.02). The changes in PaCO2 post-LVRS showed marked intersubject variability. We conclude that LVRS, by reducing hyperinflation, air trapping, and improving respiratory muscle function, enables the lung and chest wall to act more effectively as a pump, thereby increasing alveolar ventilation and reducing baseline resting PaCO2. In addition, patients with higher baseline levels of PaCO2 demonstrate the greatest reduction in PaCO2 post-LVRS, and should not be excluded from receiving LVRS.

Effect of lung volume reduction surgery on diaphragm length in severe chronic obstructive pulmonary disease.

Lung volume reduction surgery (LVRS) has been suggested as improving respiratory mechanics in patients with severe chronic obstructive pulmonary disease (COPD). We hypothesized that LVRS might lengthen the diaphragm, increase its area of apposition with the chest wall, and thereby improve its mechanical function. To determine the effect of bilateral LVRS on diaphragm length, we measured diaphragm length at TLC, using plain chest roentgenograms (CXRs), in 25 patients (11 males and 14 females) before LVRS and 3 to 6 mo after LVRS. A subgroup of seven patients (reference data) also had diaphragm length measurements made with CXRs, using films made within a year before their presurgical evaluation. Right hemidiaphragm silhouette length (PADL) and the length of the most vertically oriented portion of the right hemidiaphragm muscle (VDML) were measured. Diaphragm dome height was determined from the: (1) distance between the dome and transverse diameter at the manubrium; and (2) highest point of the dome referenced horizontally to the vertebral column. Patients also underwent spirometry, measurements of lung volumes and diffusion capacity, an incremental symptom-limited maximum exercise test, and measurements of 6 min walk distance (6MWD) and transdiaphragmatic pressures during maximum static inspiratory efforts (Pdimax sniff) and bilateral supramaximal electrophrenic twitch stimulation (Pditwitch) both before and 3 mo after LVRS. Patients were 58 +/- 8 yr of age, with severe COPD and hyperinflation (FEV1 = 0.68 +/- 0.23 L, FVC = 2.56 +/- 7.3 L, and TLC = 143 +/- 22% predicted). Following LVRS, PADL increased by 4% (from 13.9 +/- 1.9 cm to 14.5 +/- 1.7 cm; p = 0.02), VDML increased by 44% (from 2.08 +/- 1.5 cm to 3.00 +/- 1.6 cm, p = 0.01), and diaphragm dome height increased by more than 10%. In contrast, diaphragm lengths were similar in subjects with CXRs made before LVRS and within 1 yr before evaluation. The increase in diaphragm length correlated directly with postoperative reductions in TLC and RV, and also with increases in transdiaphragmatic pressure with maximal sniff (Pdimax sniff), maximal oxygen consumption (V O2max), maximal minute ventilation (V Emax), and maximum voluntary ventilation following LVRS. We conclude that LVRS leads to a significant increase in diaphragm length, especially in the area of apposition of the diaphragm with the rib cage. Diaphragm lengthening after LVRS is most likely the result of a reduction in lung volume. Increases in diaphragm length after LVRS correlate with postoperative improvements in diaphragm strength, exercise capacity, and maximum voluntary ventilation.

Improvements in lung function, exercise, and quality of life in hypercapnic COPD patients after lung volume reduction surgery.

STUDY OBJECTIVE: To determine the impact of preoperative resting hypercapnia on patient outcome after bilateral lung volume reduction surgery (LVRS). METHODS: We prospectively examined morbidity, mortality, quality of life (QOL), and physiologic outcome, including spirometry, gas exchange, and exercise performance in 15 patients with severe emphysema and a resting PaCO2 of > 45 mm Hg (group 1), and compared the results with those from 31 patients with a PaCO2 of < 45 mm Hg (group 2). RESULTS: All preoperative physiologic and QOL indices were more impaired in the hypercapnic patients than in the eucapnic patients. The hypercapnic patients exhibited a lower preoperative FEV1, a lower diffusing capacity of the lung for carbon monoxide, a lower ratio of PaO2 to the fraction of inspired oxygen, a lower 6-min walk distance, and higher oxygen requirements. However, after surgery both groups exhibited improvements in FVC (group 1, p < 0.01; group 2, p < 0.001), FEV1 (group 1, p=0.04; group 2, p < 0.001), total lung capacity (TLC; group 1, p=0.02; group 2, p < 0.001), residual volume (RV; group 1, p=0.002; group 2, p < 0.001), RV/TLC ratio (group 1, p=0.03; group 2, p < 0.001), PaCO2 (group 1, p=0.002; group 2, p=0.02), 6-min walk distance (group 1, p=0.005; group 2, p < 0.001), oxygen consumption at peak exercise (group 1, p=0.02; group 2, p=0.02), total exercise time (group 1, p=0.02; group 2, p=0.02), and the perceived overall QOL scores (group 1, p=0.001; group 2, p < 0.001). However, because the magnitude of improvement was similar in both groups, and the hypercapnic group was more impaired, the spirometry, lung volumes, and 6-min walk distance remained significantly lower post-LVRS in the hypercapnic patients. There was no difference in mortality between the groups (p=0.9). CONCLUSIONS: Patients with moderate to severe resting hypercapnia exhibit significant improvements in spirometry, gas exchange, perceived QOL, and exercise performance after bilateral LVRS. The maximal achievable improvements in postoperative lung function are related to preoperative level of function; however, the magnitude of improvement can be expected to be similar to patients with lower resting PaCO2 levels. Patients should not be excluded from LVRS based solely on the presence of resting hypercapnia. The long-term benefit of LVRS in hypercapnic patient remains to be determined.

Bilateral apical vs nonapical stapling resection during lung volume reduction surgery.

STUDY OBJECTIVES: To determine whether biapical stapling resection alone or resection of diseased, nonapical areas of emphysematous lung provides comparable physiologic outcomes or alters morbidity and mortality after lung volume reduction surgery (LVRS). DESIGN: Consecutive case-series analysis. SETTING: Urban university hospital. PATIENTS: Forty-seven patients ([mean +/- SD] aged 58+/-8 years; 18 men) with severe emphysema (FEV1, 0.7+/-0.2 L; total lung capacity [TLC], 139+/-23% predicted). INTERVENTIONS: Thirty-two patients underwent biapical LVRS, 27 by median sternotomy (MS) and 5 by video-assisted thoracoscopic surgery (VATS), and 15 underwent nonapical resection, 9 by MS and 6 by VATS. Patients were assessed for postoperative complications (respiratory tract infections, air leak duration, and death), length of stay, and physiologic parameters, which included a 6-min walk distance, spirometry, lung volume, gas exchange, diaphragm strength, and quality-of-life measures. MEASUREMENTS AND RESULTS: Patients were studied at baseline and at 3 months postoperatively. At the preoperative baseline, both groups had similar ages (57 vs 60 years; p = 0.2), 6-min walk distance (294 vs 263 m; p = 0.3), FEV1 (28% vs 29% predicted; p = 0.6), degree of hyperinflation (TLC, 138% vs 141% predicted; p = 0.8), gas exchange (PaO2/fraction of inspired oxygen, 344 vs 313, p = 0.1; PaCO2 46 vs 48 mm Hg, p = 0.4), and diaphragm strength (maximal transdiaphragmatic pressure sniff, 54 vs 46 cm H2O, p = 0.4). Resected tissue weight was similar in both groups (94 vs 93 g, p = 0.9). There were no differences in the mean percentage of change from baseline for these physiologic parameters or for quality-of-life measures between the two groups. The 6-min walk distances increased by 20% and 33%, FEV1 increased by 37% and 38%, the degrees of hyperinflation (residual volume/TLC) decreased by 16% and 15%, and the quality-of-life scores improved by 51% and 41%, respectively, in the groups that underwent biapical and nonapical resections at 3 months post-LVRS. The length of stay in the hospital for LVRS (18 vs 23 days; p = 0.4) and the duration of air leak (10 vs 15 days; p = 0.4) were also similar. Complications between the two groups (biapical vs nonapical) were similar (respiratory tract infection, 47% vs 60%, p = 0.2; reintubation, 34% vs 33%, p = 0.2; reoperation, 9% vs 20%, p = 0.4; and death, 9% vs 7%, p = 0.2). CONCLUSIONS: LVRS, by biapical or nonapical resection, produces similar improvements in lung function, exercise, diaphragm strength, and quality of life, with comparable morbidity and mortality.

Effect of lung volume reduction surgery on diaphragm strength.

Since lung volume reduction surgery (LVRS) reduces end-expiratory lung volume, we hypothesized that it may improve diaphragm strength. We evaluated 37 patients for pulmonary rehabilitation and LVRS. Before and 8 wk after pulmonary rehabilitation, 24 patients had spirometry, lung volumes, diffusion capacity, incremental symptom limited maximum exercise test, 6-min walk test, maximal static inspiratory and expiratory mouth pressures, and transdiaphragmatic pressures during maximum static inspiratory efforts and bilateral supramaximal electrophrenic twitch stimulation measured. Twenty patients (including 7 patients who crossed over after completing pulmonary rehabilitation) had baseline measurements postrehabilitation, and 3 mo post-LVRS. Patients were 58 +/- 8 yr of age, with severe COPD and hyperinflation (FEV1, 0.69 +/- 0.21 L; RV, 4.7 +/- 1.4 L). Nineteen patients had bilateral LVRS performed via median sternotomy and stapling, and 1 patient had unilateral LVRS via thorascopy with stapling. After rehabilitation, spirometry and DL(CO)/VA were not different, and lung volumes showed a slight worsening in hyperinflation. Gas exchange, 6-min walk distance, maximum oxygen uptake (VO2max), and breathing pattern during maximum exercise did not change after rehabilitation, but total exercise time was significantly longer. Inspiratory muscle strength (PImax, Pdi(max combined), Pdi(max sniff), Pdi(max), Pdi(twitch)), was unchanged after rehabilitation. In contrast, after LVRS, FVC increased 21%, FEV1 increased 34%, TLC decreased 13%, FRC decreased 23%, and FRC(trapped gas) and RV decreased by 57 and 28%, respectively. PCO2 was lower (44 +/- 6 versus 48 +/- 6 mm Hg, p < 0.003) and 6-min walk distance increased (343 +/- 79 versus 250 +/- 89 m, p < 0.001), as did total exercise time during maximum exercise (9.2 +/- 1.9 versus 6.9 +/- 2.7 min, p < 0.01). Minute ventilation (29 +/- 8 versus 21 +/- 6 L/min, p < 0.001) and tidal volume (1.0 +/- 0.33 versus 0.84 +/- 0.25 L, p < 0.001) during maximum exercise increased whereas respiratory rate was lower (28 +/- 6 versus 32 +/- 7 breaths/min, p < 0.02). Measurements of respiratory muscle strength (PImax, 74 +/- 28 versus 50 +/- 18 cm H2O, p < 0.002; Pdi(max combined), 80 +/- 25 versus 56 +/- 29 cm H2O, p < 0.01; Pdi(max sniff), 71 +/- 7 versus 46 +/- 27 cm H2O, p < 0.01; Pdi(twitch), 15 +/- 5 versus 7 +/- 5 cm H2O, p < 0.01) were all greater post-LVRS. Inspiratory muscle workload as measured by Pdi TTI was lower following LVRS (0.07 +/- 0.02 versus 0.09 +/- 0.03, p < 0.03). On multiple regression analysis, increases in PImax correlated significantly with decreases in RV and FRC(trapped gas) after LVRS (r = 0.67, p < 0.03). We conclude that LVRS significantly improves diaphragm strength that is associated with a reduction in lung volumes and an improvement in exercise performance. Future studies are needed to determine the relationship and stability of these changes over time.

Stability of improvements in exercise performance and quality of life following bilateral lung volume reduction surgery in severe COPD.

STUDY OBJECTIVE: To evaluate the long-term stability of improvements in exercise capacity and quality of life (QOL) after lung volume reduction surgery (LVRS). DESIGN: Case-series analysis. SETTING: University hospital. PATIENTS: Twenty-six patients with severe airflow obstruction (mean FEV1 of 0.67+/-0.18 L) and moderate to severe hyperinflation (mean total lung capacity of 7.30+/-1.90 L). INTERVENTION AND MEASUREMENTS: All patients underwent bilateral LVRS via median sternotomy. Serial measurement of lung function, symptom-limited cardiopulmonary exercise tests, 6-min walk distances (6MWD), and sickness impact profile (SIP) scores were done before, and at 3, 6, 12, and 18 months after surgery. RESULTS: FEV1 (0.93+/-0.29 vs 0.68+/-0.19 L, p<0.001) increased while residual volume (3.47+/-1.2 vs 4.77+/-1.5 L, p<0.001) decreased significantly at 3 months post-LVRS compared to baseline, and these changes were maintained at 12 to 18 months follow-up. Similarly, the increase in 6MWD at 3 months post-LVRS (340+/-84 vs 251+/-114 m, p<0.001) was sustained at all follow-up times. On cardiopulmonary exercise testing, total exercise time (9.0+/-1.8 vs 6.1+/-1.9 min, p<0.001), oxygen uptake at peak exercise (VO2 peak) (14.9+/-4 vs 11.9+/-3 mL/kg/min, p<0.001), maximum oxygen pulse (7.43+/-2.37 vs 5.85+/-1.96 mL/beat, p<0.005), and maximum minute ventilation (VEmax) (30.3+/-10 vs 23.5+/-7.1 L/min, p<0.001) increased significantly at 3 months post-LVRS. On serial study following LVRS, total exercise time remained significantly greater at 6 (8.5+/-1.38 min) and 12 months (8.71+/-2.0 min) post-LVRS compared to baseline (5.81+/-1.9 min, p<0.05). VO2 peak tended to be higher at all follow-up periods (3 months, 16.1+/-4.3; 6 months, 14.5+/-2.6; 12 months, 14.1+/-3.5 mL/kg) compared to baseline (12.6+/-3.9 mL/kg, p=0.08). Similarly, maximum O2 pulse tended to be higher in all follow-up studies (3 months, 8.45+/-2.7; 6 months, 7.6+/-1.7; 12 months, 7.42+/-2.1 mL/beat) compared to baseline (6.39+/-2.5 mL/beat, p=0.06). Higher VEmax continued to be observed at 6 (30+/-10 L/min) and 12 months (28+/-10 L/min) post-LVRS, compared to baseline (23+/-7 L/min, p=0.02). VEmax post-LVRS was significantly higher at 3 and 6 months compared to baseline on post-hoc analysis (p<0.05). Overall SIP scores were lower at 3 months (7 vs 18, p<0.0002) post-LVRS and were sustained in long-term follow-up. CONCLUSION: We conclude that bilateral LVRS via median sternotomy in selected patients with severe, diffuse emphysema improves exercise performance and QOL at 3 months following LVRS and these improvements are maintained for at least 12 to 18 months in follow-up.

Biotransformation in monkey brain: coupling of sulfation to glutathione conjugation.

Phenol sulfotransferase (PST, EC 2.8.2.1) and glutathione-S-transferase (GST, EC 2.5.1.18), the phase II biotransformation enzymes inactivate many exo- and endogenous compounds. The effect of PST substrates (catecholamines, simple phenols, selected phenolic drugs) and PST products (phenolic sulfates) on GST activity was investigated to identify possible interactions between sulfation and glutathione conjugation in the brain. Two soluble forms of PST and two forms of GST were isolated from monkey (Rhesus macacus) brain cortex. Catecholamines, hypertensive and hypotensive drugs which are sulfated by monkey brain PSTs slightly inhibit the activity of brain GSTs. The greatest inhibitory effect was observed with neurotoxic compounds such as 6-OHDA and manganese. The commonly used analgesic drugs inhibit both GST forms. These enzymes are also inhibited by phenacetin, the precursor of paracetamol, and prototype salicylates such as sodium salicylate and acetylsalicylic acid. The effect of simple phenols and their sulfated metabolites on GST activity varies. The obtained results point to a possible interaction between sulfation and glutathione conjugation in vivo since many physiologically, therapeutically and toxicologically active compounds which are sulfated by brain phenol sulfotransferases may be bound by brain glutathione-S-transferases. These compounds may lose their activity (on being bound to GST) and expose the brain to the toxic electrophiles (by decreasing GST activity).

Gastric dilatation-volvulus in the dog with histological evidence of preexisting inflammatory bowel disease: a retrospective study of 23 cases.

The gastric dilatation-volvulus (GDV) syndrome in the dog is considered to be multifactorial. The medical records of 42 dogs treated for GDV between 1990 and 1994 were reviewed in an effort to evaluate the correlation between GDV and preexisting gastrointestinal disease. Twenty-three cases fit the inclusion criteria of an intestinal biopsy taken at the time of corrective surgery and a complete medical history. The microscopic jejunal changes expected from the acute vascular compromise in these animals were diffuse edema, dilatation of lymphatics with possible lymphangiectasia, mucosal degeneration, diapedesis of neutrophils, and rare hemorrhage. These changes were discounted. Of the 23 biopsies, 14 (61%) were consistent with the presence of an underlying inflammatory disease, and of these 14, 12 (86%) were accompanied by case histories of prior gastrointestinal disturbances. This study raises the possibility of an association between GDV and inflammatory bowel disease.

[Examination of human neutrophil activation in hyperlipidemia]. / Badanie aktywnosci ludzkich granulocytów obojetnochlonnych w hiperlipidemii.

Chemotaxis, spontaneous migration, phagocytosis, expression of the receptors of Fc Ig fragments and of C3 component of complement has been examined in blood of 51 patients with obesity divided into 3 groups with: 1. disturbances in carbohydrate and lipid metabolism, 2. disturbance in lipid metabolism, 3. no symptoms of metabolic diseases and 20 healthy controls. A comparison of the characteristics of neutral granulocytes in the blood of the healthy controls before and after fat rich meal has been performed. Obtained results indicate that high concentration of lipids, decrease granulocyte activity therefore could be the cause of the decrease of immunological defence.

Sulfation of hypertensive and hypotensive drugs by monkey brain phenol sulfotransferase.

The substrate specificity and affinity of two forms of phenol sulfotransferase (PST) from Rhesus macaque brain cortex were studied. Catecholamines, their methylated metabolites (normetanephrine, metanephrine) and methylated precursor, alpha-methylDOPA, were examined as substrates for both the cationic (PST I) and the anionic (PST II) forms of the enzyme. Sulfation of hypertensive drugs (phenylephrine, octopamine, metaraminol), hypotensive drugs (alpha-methylDOPA, minoxidil), and related agents without a free hydroxy group on the benzene ring were also studied. Results indicated that both PST forms sulfated alpha-methylDOPA and minoxidil, but only PST II transferred the sulfate group to catecholamines and most of the adrenergic agents examined.