Biomedical subjects

S Cooper

Publications and source records attributed to S Cooper.

At least 37 records · Page 2Linked to original sources

PubMed1999

Abnormal chemokine-induced responses of immature and mature hematopoietic cells from motheaten mice implicate the protein tyrosine phosphatase SHP-1 in chemokine responses.

Chemokines regulate a number of biological processes, including trafficking of diverse leukocytes and proliferation of myeloid progenitor cells. SHP-1 (Src homology 2 domain tyrosine phosphatase 1), a phosphotyrosine phosphatase, is considered an important regulator of signaling for a number of cytokine receptors. Since specific tyrosine phosphorylation of proteins is important for biological activities induced by chemokines, we examined the role of SHP-1 in functions of chemokines using viable motheaten (me(v)/me(v)) mice that were deficient in SHP-1. Chemotactic responses to stromal call-derived factor 1 (SDF-1), a CXC chemokine, were enhanced with bone marrow myeloid progenitor cells as well as macrophages, T cells, and B cells from me(v)/me(v) versus wild-type (+/+) mice. SDF-1-dependent actin polymerization and activation of mitogen-activated protein kinases were also greater in me(v)/me(v) versus +/+ cells. In contrast, immature subsets of me(v)/me(v) bone marrow myeloid progenitors were resistant to effects of a number of chemokines that suppressed proliferation of +/+ progenitors. These altered chemokine responses did not appear to be due to enhanced expression of CXCR4 or lack of chemokine receptor expression. However, expression of some chemokine receptors (CCR1, CCR2, CCR3, and CXCR2) was significantly enhanced in me(v)/me(v) T cells. Our results implicate SHP-1 involvement in a number of different chemokine-induced biological activities.

Actins↗

PubMed1999

Dominant myelopoietic effector functions mediated by chemokine receptor CCR1.

Macrophage inflammatory protein (MIP)-1alpha, a CC chemokine, enhances proliferation of mature subsets of myeloid progenitor cells (MPCs), suppresses proliferation of immature MPCs, and mobilizes mature and immature MPCs to the blood. MIP-1alpha binds at least three chemokine receptors. To determine if CCR1 was dominantly mediating the above activities of MIP-1alpha, CCR1-deficient (-/-) mice, produced by targeted gene disruption, were used. MIP-1alpha enhanced colony formation of marrow granulocyte/macrophage colony-forming units (CFU-GM), responsive to stimulation by granulocyte/macrophage colony-stimulating factor (GM-CSF), and CFU-M, responsive to stimulation by M-CSF, from littermate control CCR1(+/+) but not CCR1(-/-) mice. Moreover, MIP-1alpha did not mobilize MPCs to the blood or synergize with G-CSF in this effect in CCR1(-/-) mice. However, CCR1(-/-) mice were increased in sensitivity to MPC mobilizing effects of G-CSF. Multi-growth factor-stimulated MPCs in CCR1(-/-) and CCR1(+/+) marrow were equally sensitive to inhibition by MIP-1alpha. These results implicate CCR1 as a dominant receptor for MIP-1alpha enhancement of proliferation of lineage-committed MPCs and for mobilization of MPCs to the blood. CCR1 is not a dominant receptor for MIP-1alpha suppression of MPC proliferation, but it does negatively impact G-CSF-induced MPC mobilization.

Animals↗

PubMed1999

Role of the His273 located in the sixth transmembrane domain of the angiotensin II receptor subtype AT2 in ligand-receptor interaction.

Angiotensin II receptor subtypes AT1 and AT2 are proteins with seven transmembrane domain (TMD) topology and share 34% homology. It was shown that His256, located in the sixth TMD of the AT1 receptor, is needed for the agonist activation by the Phe8 side chain of angiotensin II, although replacing this residue with arginine or glutamine did not significantly alter the affinity binding of the receptor. We hypothesized that the His273 located in the sixth transmembrane domain of the AT2 receptor may play a similar role in the functions of the AT2 receptor, although this residue was not identified as a conserved residue in the initial homology comparisions. Therefore, we replaced His273 of the AT2 receptor with arginine or glutamine and analyzed the ligand-binding properties of the mutant receptors using Xenopus oocytes as an expression system. Our results suggested that the AT2 receptor mutants His273Arg and His273 Glu have lost their affinity to [125I-Sar1-Ile8]Ang II, a peptidic ligand that binds both the AT1 and AT2 receptors and to 125I-CGP42112A, a peptidic ligand that binds specifically to the AT2 receptor. Thus, His273 located in the sixth TMD of the AT2 receptor seems to play an important role in determining the binding properties of this receptor. Moreover, these results along with our previous observation that the Lys215 located in the 5th TMD of the AT2 receptor is essential for its high affinity binding to [125I-Sar1-Ile8]Ang II indicate that key amino acids located in the 5th and 6th TMDs of the AT2 receptor are needed for high affinity binding of the AT2 to its ligands.

Amino Acid Substitution↗

PubMed1999

Enhanced myeloid progenitor cell cycling and apoptosis in mice lacking the chemokine receptor, CCR2.

Chemokines regulate hematopoiesis in part by influencing the proliferative status of myeloid progenitor cells (MPC). Human MCP-1/murine JE, a myelosuppressive chemokine, specifically binds C-C chemokine receptor 2 (CCR2). Transgenic mice containing a targeted disruption in CCR2 that prevents expression of CCR2 mRNA and protein and have MPC that are insensitive to inhibition by MCP-1 and JE in vitro were assessed for potential abnormalities in growth of bone marrow (BM) and spleen MPC. MPC in both unseparated and c-kit+lin- populations of BM from CCR2-deficient (-/-) mice were in a greatly increased proliferation state compared with CCR2 littermate control (+/+) mice, an effect not apparent with progenitors from spleens of CCR2 (-/-) mice. Increased cycling status of CCR2 (-/-) BM MPC did not result in increased numbers of nucleated cells or MPC in BM or spleens of CCR2 (-/-) mice. Possible reasons for this apparent discrepancy were highlighted by flow cytometric analysis of c-kit+lin- BM cells and colony formation by MPC subjected to delayed addition of growth factors. The c-kit+lin- population of BM cells from CCR2 (-/-) mice had a significantly higher percentage of apoptotic cells than those from CCR2 (+/+) BM. However, elevated apoptosis was not associated with decreased numbers of c-kit+lin- cells. The increased percentage of apoptotic c-kit+lin- cells was due to elevated apoptosis within the c-kitdimlin-, but not the c-kitbrightlin-, subpopulations of cells. Consistent with enhanced apoptosis of phenotypically defined cells, MPC from CCR2 (-/-) BM and purified c-kit+lin- cells demonstrated decreased cell survival in vitro upon delayed addition of growth factors. The data suggest that signals received by CCR2 limit proliferation of progenitor cells in the BM, but also enhance survival of these cells.

Animals↗

PubMed1999

Role of the third intracellular loop of the angiotensin II receptor subtype AT2 in ligand-receptor interaction.

Angiotensin II (Ang II) receptor subtypes AT1 and AT2 share 34% overall homology, but the least homology is in their third intracellular loop (3rd ICL). In an attempt to elucidate the role of the 3rd ICL in determining the similarities and differences in the functions of the AT1 and the AT2 receptors, we generated a chimeric receptor in which the 3rd ICL of the AT2 receptor was replaced with that of the AT1 receptor. Ligand-binding properties and signaling properties of this receptor were assayed by expressing this receptor in Xenopus oocytes. Ligand-binding studies using [125I-Sar1-Ile8] Ang II, a peptidic ligand that binds both the AT1 and the AT2 receptor subtypes, and 125I-CGP42112A, a peptidic ligand that is specific for the AT2 receptor, showed that the chimeric receptor has lost affinity to both ligands. However, IP3 levels of the oocytes expressing the chimeric receptor were comparable to the IP3 levels of the oocytes expressing the AT1 receptor, suggesting that the chimeric receptors could couple to phospholipase C pathway in response to Ang II. We have shown previously that the nature of the amino acid present in the position 215 located in the fifth transmembrane domain (TMD) of the AT2 receptor plays an important role in determining its affinity to different ligands. Our results from the ligand-binding studies of the chimeric receptor further support the idea that the structural organization of the region spanning the 5th TMD and the 3rd ICL of the AT2 receptor has an important role in determining the ligand-binding properties of this receptor.

Amino Acid Sequence↗

PubMed1999

Inhibition of proprotein convertases-1, -7 and furin by diterpines of Andrographis paniculata and their succinoyl esters.

Studies were performed to investigate the prohormone/proprotein convertase (PC)-inhibitory properties of chemical constituents of the medicinally active plant Andrographis paniculata (AP; from the family Acanthaceae), also known as 'King of Bitters'. Among the individual components tested against the clinically important convertases, furin and PC1, neoandrographolide (a C3 O-glucoside derivative of the major constituent andrographolide) exhibited the highest inhibitory action with an IC50 of 53.5 microM against furin. The data further revealed that although andrographolide, the major bitter principle of AP, exhibited a relatively small enzyme inhibition (IC50=1.0 mM and Ki=200 microM against furin), upon succinoylation, its inhibitory action against the above convertases was enhanced significantly with a Ki in the low micromolar range (<30 microM), suggesting that a specific structural modification of the andrographolide skeleton may be exploited to develop a new class of non-peptide inhibitors of PCs. When tested against PC7, these succinoylated derivatives of andrographolide also displayed strong inhibitory action, with Ki values again in the low micromolar range. This potentially interesting observation may be attributed to the reported anti-HIV property of 14-dehydroandrographolide succinic acid monoester (DASM). It is suggested here that DASM, by virtue of this protease inhibitory property, possibly acts by suppressing the proteolytic cleavage of envelope glycoprotein gp160 of HIV, which is known to be PC-mediated, particularly by furin and PC7.

Anti-HIV Agents↗

PubMed1999

Hepatitis C virus envelope glycoprotein E1 originates in the endoplasmic reticulum and requires cytoplasmic processing for presentation by class I MHC molecules.

We investigated whether hepatitis C virus envelope glycoprotein E1 is transported from the endoplasmic reticulum (ER) to the cytoplasm of infected cells for class I MHC processing. Target cells expressing E1 were killed by CTL lines from a hepatitis C virus-infected chimpanzee, and synthetic peptides were used to define an epitope (amino acids 233-GNASRCWVA-241) presented by the Patr-B*1601 class I MHC molecule. An unusually high concentration (>100 nM) of this nonameric peptide was required for target cell lysis, but this could be reduced at least 1000-fold by replacing the asparagine at amino acid position 234 (Asn234) with aspartic acid (Asp), the anticipated anchor residue for NH2-terminal peptide binding to Patr-B*1601. Conspicuously, position 234 is part of an N-glycosylation motif (Asn-Xaa-Ser/Thr), suggesting that the Asn234 to Asp substitution might occur naturally within the cell due to deglycosylation/deamidation of this amino acid by the cytosolic enzyme peptide N-glycanase. In support of this model, we demonstrate that presentation of the epitope depended on 1) cotranslational synthesis of E1 in the ER, 2) glycosylation of the E1 molecule, and 3) a functional TAP transporter to shuttle peptide from the cytosolic to ER compartment. These results indicate for the first time that during infection of the host, viral envelope glycoproteins originating in the ER are processed in the cytoplasm for class I MHC presentation. That a posttranslational change in amino acid sequence from Asn to Asp alters the repertoire of peptides presented to CD8+ CTL has implications for the design of antiviral vaccines.

Animals↗

PubMed1999

Systematic relationships within the dasyurid marsupial tribe Sminthopsini--a multigene approach.

We report analyses of complete DNA sequences of the mitochondrial cytochrome b (1146 bp), 12S rRNA (974 bp), partial control region (371 bp) loci, and the nuclear protamine P1 (616 bp) gene from all but one species (Sminthopsis butleri) of the dasyurid marsupial tribe Sminthopsini, as well as several outgroups. Parsimony analyses of combined nuclear and mitochondrial data suggest that Antechinomys is sister to a clade consisting of Sminthopsis and Ningaui. Parsimony, maximum-likelihood, and mixed-model distance analyses consistently resolve several species groups within Sminthopsis. The Macroura group includes S. macroura, S. virginiae, S. douglasi, and S. bindi; S. butleri is also included here on the basis of partial 12S rRNA sequences. S. crassicaudata is resolved as sister to the Macroura clade. The Murina group includes S. murina, S. leucopus, S. gilberti, S. dolichura, and S. archeri. S. griseoventer and S. aitkeni are resolved as a clade, and there is moderate support for a group consisting of the genetically divergent species S. psammophila, S. hirtipes, S. youngsoni, and S. ooldea (possibly along with S. longicaudata and S. granulipes). Compositions of species groups are partially congruent with clades previously proposed on the basis of morphological data. Radiations within Sminthopsini appear to be coincident with major environmental changes since the mid-Miocene.

Animals↗

PubMed1999

Leadership of resuscitation teams: "Lighthouse Leadership'.

AIM: The purpose of this study was to determine the relationship between leadership behaviour, team dynamics and task performance. METHODS: This was as an observational study, using video recordings of 20 resuscitation attempts. The Leadership Behaviour Description Questionnaire (LBDQ) was used to measure the level of structure built within the team. Interpersonal behaviour and the tasks of resuscitation were measured with a team dynamics and a task performance scale. The degree to which the leader actively participated, 'hands on', with the tasks of resuscitation, and their previous training in advanced life support (ALS), and experience of resuscitation attempts, were evaluated against the leadership rating. RESULTS: The degree to which the leader built a structure within the team was found to correlate significantly with the team dynamics (P = 0.000) and the task performance (P = 0.013). Where the leaders participated 'hands on' they were less likely to build a structured team (P = 0.005), the team were less dynamic (P = 0.028) and the tasks of resuscitation were performed less effectively (P = 0.099). Experience gained over a 1-year period did not enhance leadership performance, but leaders who had up to 3 years experience were more likely to be effective in this role (P = 0.072). Interestingly, ALS training did not enhance leadership performance per se. However those leaders who had had recent ALS training were more likely not to participate 'hands on' (P = 0.035). There were some notable shortcomings in the performance of the task and some interesting correlations relating to duration of resuscitation, survival rate estimations, the leaders' attitudes and the teams' level of experience. CONCLUSION: Leaders must build a structure within a resuscitation team in order for them to perform effectively. An emergency leadership training programme is essential to enhance the performance of leaders and their teams.

Cardiopulmonary Resuscitation↗

PubMed1999

Analysis of a successful immune response against hepatitis C virus.

To investigate the type of immunity responsible for resolution of hepatitis C virus (HCV) infection, we monitored antibody and intrahepatic cytotoxic T lymphocyte (CTL) responses during acute (<20 weeks) infection in chimpanzees. Two animals who terminated infection made strong CTL but poor antibody responses. In both resolvers, CTL targeted at least six viral regions. In contrast, animals developing chronic hepatitis generated weaker acute CTL responses. Extensive analysis of the fine specificity of the CTL in one resolver revealed nine peptide epitopes and restriction by all six MHC class I allotypes. Every specificity shown during acute hepatitis persisted in normal liver tissue more than 1 yr after resolution. These results suggest that CD8+CTL are better correlated with protection against HCV infection than antibodies.

Acute Disease↗

PubMed1999

Gastrointestinal safety and tolerance of ibuprofen at maximum over-the-counter dose.

BACKGROUND: Delineation of non-steroidal anti-inflammatory drug (NSAID) gastrointestinal toxicity has largely depended on retrospective epidemiologic studies which demonstrate that lower doses of NSAIDs pose a lower risk of gastrointestinal toxicity. Ibuprofen, a propionic acid NSAID, has, in most such studies, exhibited a favourable profile in terms of gastrointestinal bleeding. Since 1984, ibuprofen has been available as a non-prescription analgesic/antipyretic with a limit of 1200 mg/day for 10 days of continuous use. Trials and spontaneously reported adverse experiences suggest that gastrointestinal symptoms and bleeding are rare. METHODS: This study prospectively evaluated the gastrointestinal tolerability, as compared to placebo, of the maximum non-prescription dose and duration of ibuprofen use in healthy subjects representative of a non-prescription analgesic user population. RESULTS: Gastrointestinal adverse experiences were similar in the placebo and ibuprofen groups (67 out of 413, 16% with placebo vs. 161 out of 833, 19% with ibuprofen). There was no difference between the two groups in the proportion discontinuing due to a gastrointestinal event. Gastrointestinal adverse experiences reported by >/= 1% of subjects were: dyspepsia, abdominal pain, nausea, diarrhoea, flatulence, and constipation. Seventeen (1.4%) subjects had positive occult blood tests: their frequency was comparable between treatments. CONCLUSIONS: When used as directed to treat episodic pain, non-prescription ibuprofen at the maximum dose of 1200 mg/day for 10 days, is well-tolerated.

Adolescent↗

PubMed1999

Brief therapy in college counseling and mental health.

Several factors have converged to make brief counseling and therapy the preferred mode of individual service delivery for college counseling and mental health services. The authors introduce the topic of brief therapy, offer a rationale for its use in college contexts, and discuss significant issues, research findings, and therapist attitudes in support of successful use of these approaches. This is followed by a description of issues of implementation, including assessment processes, interventions (short-term intermittent approaches, very brief therapy, single-session counseling, crisis intervention within brief therapy, connections with multiculturally oriented psychology, and brief group therapy), and referral issues. General conclusions about brief therapy in college settings and recommendations for research on furthering use of these approaches are offered.

Counseling↗

PubMed1999

Phosphorylation-dephosphorylation of retinoblastoma protein not necessary for passage through the mammalian cell division cycle.

Phosphorylation of the retinoblastoma protein (Rb) during the G1-phase of the mammalian cell division cycle is currently believed to be a controlling element regulating the passage of cells into S-phase. We find, however, that the suspension-grown cell lines U937, L1210, and MOLT-4 contain exclusively hyperphosphorylated Rb. Furthermore, when adherent NIH3T3 cells are grown at very low densities to avoid overgrowth and contact inhibition, they also contain only hyperphosphorylated Rb. NIH3T3 cells exhibit hypophosphorylation when the cells are grown at moderate to high cell densities. We propose that cultures of adherent cells such as NIH3T3, when grown to moderate cell densities, are made up of two populations of cells: (a) cells that are relatively isolated and therefore growing exponentially without contact inhibition, and (b) cells that are growth-inhibited by local cell density or contact inhibition. The common observation in adherent cell lines, that Rb is both hyper- and hypophosphorylated in the G1-phase and only hyperphosphorylated in the S- and G2-phases, is explained by the effects of cell density and contact inhibition. Thus, phosphorylation-dephosphorylation of Rb protein during the G1 phase is not a necessary process during the NIH3T3, L1210, MOLT-4, and U937 division cycles. We propose that phosphorylation-dephosphorylation of Rb is independent of the division cycle and is primarily determined by growth conditions throughout the division cycle.

3T3 Cells↗

PubMed1999

Injury control strategies: extending the quality and quantity of data relating to road traffic accidents in children.

This review describes how an extended database of information can provide the opportunity to go beyond the traditionally distinct health, engineering, and education initiatives in order to identify the effectiveness of more overarching policies for injury control. Such information can be used to raise awareness and to encourage community participation in designing a road traffic accident prevention strategy.

Accidents, Traffic↗

PubMed1999

Morbidity from asthma in relation to regular treatment: a community based study.

BACKGROUND: The extent to which asthma morbidity in the community occurs in patients who are having relatively little treatment or in those on step 3 or above of the British asthma management guidelines is uncertain. We have looked at this in a community population in southern Nottinghamshire. METHODS: A cross sectional review of treatment in all patients over the age of four with diagnosed asthma was carried out in five large general practices (population 38 865) in 1995/6 using computerised general practice records. The patients' usual treatment was obtained from prescription data and categorised by the appropriate step on the British guidelines on asthma management. Two measures of morbidity, the request for 10 or more short acting beta agonist inhalers a year or the need for a course of oral corticosteroids in the last year, were related to the regular treatment of the patients. RESULTS: Of the 3373 patients (8. 7%) given a diagnosis of asthma, the percentage on steps 1, 2, 3, 4, and 5 of treatment were 54%, 22%, 11%, 3.6%, and 1%, respectively, with a further 8% having had no treatment. During the past year 13. 6% had been prescribed 10 or more beta agonist inhalers and 12.5% had received at least one course of oral corticosteroids. Both measures occurred more frequently in patients taking more prophylactic treatment (step 3 or above). Nevertheless, because most patients were on steps 1 and 2 of the treatment guidelines, more than half the patients requiring high doses of inhaled beta agonists or a course of oral prednisolone came from those taking low dose or no regular inhaled corticosteroid. CONCLUSIONS: Evidence of morbidity from asthma was found in many patients taking little or no prophylactic medication and this should be amenable to improved education. A different approach may be needed for patients with continuing morbidity who are already taking higher doses of prophylactic medication.

Adolescent↗

PubMed1999

Altered responsiveness to chemokines due to targeted disruption of SHIP.

SHIP has been implicated in negative signaling in a number of hematopoietic cell types and is postulated to downregulate phosphatidylinositol-3-kinase- (PI-3K-) initiated events in diverse receptor signaling pathways. Because PI-3K is implicated in chemokine signaling, we investigated whether SHIP plays any role in cellular responses to chemokines. We found that a number of immature and mature hematopoietic cells from SHIP-deficient mice manifested enhanced directional migration (chemotaxis) in response to the chemokines stromal cell-derived factor-1 (SDF-1) and B-lymphocyte chemoattractant (BLC). SHIP(-/-) cells were also more active in calcium influx and actin polymerization in response to SDF-1. However, colony formation by SHIP-deficient hematopoietic progenitor cell (HPCs) was not inhibited by 13 myelosuppressive chemokines that normally inhibit proliferation of HPCs. These altered biologic activities of chemokines on SHIP-deficient cells are not caused by simple modulation of chemokine receptor expression in SHIP-deficient mice, implicating SHIP in the modulation of chemokine-induced signaling and downstream effects.

Actins↗

PubMed1999

Pharmacokinetic and pharmacodynamic action of etodolac in patients after oral surgery.

The objective of this double-blind, randomized, parallel-group study was to evaluate the pharmacokinetics of etodolac and the pharmacodynamic response of pain in patients following oral surgery who had received 200 or 400 mg of etodolac immediate release (IR), 400 or 1200 mg of etodolac extended release (ER), or a placebo. Etodolac concentrations in 441 plasma samples from 187 patients were analyzed for population pharmacokinetics using the NONMEM program. A one-compartment pharmacokinetic model with first-order absorption described the observed data. For etodolac IR, the population mean (%CV) estimates were 3.01 L/h (5.3%) for clearance, 13.6 L (6.8%) for volume of distribution, and 2.31 h-1 (33%) for ka. Respective values for etodolac ER were 3.68 L/h (11%) for clearance, 24.3 L (22%) for volume of distribution, and 0.172 h-1 (24%) for ka. These values generally agreed with previously reported values in healthy adults. Pharmacodynamic assessments included collection of a four-level categorical rating of pain intensity for up to 24 hours after treatment. Pain intensity difference scores were temporally related to etodolac concentrations and were described using an indirect response model. Mean (%CV) pharmacodynamic parameters were IC50 of 14.0 mg/L (9.5%), kout of 1.62 h-1 (13%), FR of 0.56 (8.2%), and Hill coefficients that ranged from 1.26 to 3.34 units. A single 1200 mg dose of etodolac ER given once daily was shown to provide substantial efficacy for 13 hours after dose, modest effect through 24 hours, and a more sustained duration of action than the IR dosage form.

Adolescent↗

PubMed1999

A pilot study of expiratory flow limitation and lung volume reduction surgery.

STUDY OBJECTIVES: To examine the relationships between changes in expiratory flow limitation (FL) during anesthesia and postoperative responses to lung volume reduction surgery (LVRS). DESIGN: Prospective consecutive case comparison. SETTING: University medical center. PATIENTS: Eight patients with severe emphysema. INTERVENTIONS: General anesthesia with muscle paralysis and thoracic epidural analgesia were provided for LVRS via median sternotomy. MEASUREMENTS: FEV(1), functional residual capacity (FRC), and total lung capacity (TLC) were measured preoperatively and 3 months postoperatively. Tidal volume (VT) flow/volume (F/V) curves were obtained with a Pitot-type spirometer. VT, expiratory flow rate at 0. 25 x VT (V'VT,25% ), and peak expiratory flow rate (V'VT,MAX) were obtained from VT F/V curves to derive V'VT,25%/V'VT,MAX ratio as a measure of FL. RESULTS: Closed chest VT F/V curves during anesthesia pre-LVRS showed four patients with FL (group A) whose V'VT,25%/V'VT, MAX ratio was 0.38 +/- 0.06 (mean +/- SD) and four patients without FL (group B) whose V'VT,25%/V'VT,MAX ratio was 0.82 +/- 0.06 (p = 0. 0001). Closed chest post-LVRS V'VT,25%/V'VT,MAX ratio during anesthesia increased by 0.48 +/- 0.08 in group A, compared with a 0. 19 +/- 0.16 reduction in group B (p = 0.0001). Preoperative FEV(1) was 0.57 +/- 0.10 L for group A vs 0.82 +/- 0.13 L for group B (p = 0.02). Postoperative FEV(1) increased by 67 +/- 40% for group A (p = 0.03) vs 29 +/- 21% for group B (not significant). FRC decreased by 33 +/- 3% for group A vs 17 +/- 5% for group B (p = 0.0007), and FRC/TLC decreased by 0.14 +/- 0.05 for group A vs 0.01 +/- 0.07 for group B (p = 0.026). Post-LVRS V'VT,25%/V'VT,MAX ratio change during anesthesia correlated with postoperative reduction in FRC (r(2) = 0. 89, p = 0.0004) and FRC/TLC (r(2) = 0.52, p = 0.045). CONCLUSION: Post-LVRS change in V'VT,25%/V'VT,MAX ratio during anesthesia showed a linear relationship with 3-month postoperative improvement in dynamic hyperinflation. Thus, V'VT,25%/V'VT,MAX ratio may help provide valuable insights into the interactions between chest wall recoil, dynamic hyperinflation, and VT flow rates in patients with severe COPD and LVRS.

Aged↗