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B T Thompson

Publications and source records attributed to B T Thompson.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin-10 polymorphism in position -1082 and acute respiratory distress syndrome.

The GG genotype of the interleukin (IL)-10 promoter polymorphism in position -1082 (-1082GG) has been associated with increased IL-10 production. The current authors hypothesised that the -1082GG genotype is associated with the development of, and outcomes in, acute respiratory distress syndrome (ARDS). A nested case-control study was conducted in 211 Caucasian cases of ARDS and 429 controls who were admitted to an intensive care unit with sepsis, trauma, aspiration or massive transfusions. Cases were followed for organ failure and 60-day mortality. The -1082GG genotype was associated with the development of ARDS, but only in the presence of a significant interaction between the -1082GG genotype and age. Among patients with ARDS, the -1082GG genotype was associated with decreased severity of illness on admission, lower daily organ dysfunction scores and lower 60-day mortality. In conclusion, the high interleukin-10-producing -1082GG genotype may be associated with variable odds for acute respiratory distress syndrome development depending on age. Among those with acute respiratory distress syndrome, the -1082GG genotype is associated with lower mortality and organ failure. Further studies are needed to confirm these findings.

Adolescent↗
PubMed2005

-308GA and TNFB polymorphisms in acute respiratory distress syndrome.

The -308GA and TNFB1/2 polymorphisms of the tumour necrosis factor genes have been associated with increased susceptibility to, and mortality in sepsis, although, prior studies are not consistent. Their role in acute respiratory distress syndrome (ARDS) has not been evaluated. The current authors hypothesised that the -308A allele and TNFB22 genotype would be associated with increased susceptibility to, and mortality in ARDS. The above hypothesis was investigated in a nested case-control study of 441 Caucasian controls and 212 cases admitted to an intensive care unit with sepsis, trauma, aspiration or hyper-transfusions. The -308A and TNFB1 alleles were in linkage disequilibrium. These polymorphisms were not associated with ARDS susceptibility on crude analysis. On subgroup analyses, they were associated with either increased or decreased odds of developing ARDS depending on whether the clinical risk for ARDS results in direct or indirect pulmonary injury. The -308A allele was associated with increased 60-day mortality in ARDS, with the strongest association found among younger patients. There was no association between the TNFB polymorphism and ARDS mortality. The -308GA, but not the TNFB12, polymorphism was associated with increased mortality in acute respiratory distress syndrome, but their association with acute respiratory distress syndrome susceptibility depended on the site of injury predisposing to acute respiratory distress syndrome.

APACHE↗
PubMed2001

Clinicians' approaches to mechanical ventilation in acute lung injury and ARDS.

STUDY OBJECTIVES: To examine clinicians' approaches to mechanical ventilation in patients with acute lung injury (ALI; PaO(2)/fraction of inspired oxygen [FIO(2)] 35 cm H(2)O in 26% of patients. Seventy-eight percent of patients with ARDS received <or= 10 cm H(2)O of positive end-expiratory pressure. CONCLUSIONS: Physicians in ARDS Network centers caring for patients early in the course of ALI/ARDS used volume-targeted ventilation and selected tidal volumes that resulted in Pplats generally < 35 cm H(2)O. The average tidal volume was similar for patients with ARDS vs those with milder oxygenation deficits.

Airway Resistance↗
PubMed2000

Structural determinants of antiproliferative activity of heparin on pulmonary artery smooth muscle cells.

In addition to its anticoagulant properties, heparin (HP), a complex polysaccharide covalently linked to a protein core, inhibits proliferation of several cell types including pulmonary artery smooth muscle cells (PASMCs). Commercial lots of HP exhibit varying degrees of antiproliferative activity on PASMCs that may due to structural differences in the lots. Fractionation of a potent antiproliferative HP preparation into high and low molecular weight components does not alter the antiproliferative effect on PASMCs, suggesting that the size of HP is not the major determinant of this biological activity. The protein core of HP obtained by cleaving the carbohydrate-protein linkage has no growth inhibition on PASMCs, demonstrating that the antiproliferative activity resides in the glycosaminoglycan component. Basic sugar residues of glucosamine can be replaced with another basic sugar, i.e., galactosamine, without affecting growth inhibition of PASMCs. N-sulfonate groups on these sugar residues of HP are not essential for growth inhibition. However, O-sulfonate groups on both sugar residues are essential for the antiproliferative activity on PASMCs. In whole HP, in contrast to an earlier finding based on a synthetic pentasaccharide of HP, 3-O-sulfonation is not critical for the antiproliferative activity against PASMCs. The amounts and distribution of sulfonate groups on both sugar residues of the glycosaminoglycan chain are the major determinant of antiproliferative activity.

Animals↗
PubMed1999

Effect of fully sulfated glycosaminoglycans on pulmonary artery smooth muscle cell proliferation.

Fully sulfated heparin and other glycosaminoglycans, namely heparan, chondroitin, and dermatan sulfates, and hyaluronan have been prepared by using sulfur trioxide under mild chemical conditions. All these derivatives were assayed for antiproliferative activity on cultured bovine pulmonary artery smooth muscle cells (BPASMCs). No appreciable difference was found between heparin and fully sulfated heparin. Chondroitin and dermatan sulfates actually stimulated BPASMCs growth but full sulfonation made them strongly antiproliferative. Native hyaluronan was not antiproliferative but became strongly so after sulfonation. Neither acharan sulfate nor N-sulfoacharan sulfate had any antiproliferative activity. This suggests that O-sulfonation of the polysaccharide is critical for antiproliferative activity, whereas N-sulfonation of glucosamine residues is not.

Animals↗
PubMed1999

Olanzapine overdose with serum concentrations.

Olanzapine, a new atypical antipsychotic drug, has been prescribed in the treatment of schizophrenia and psychotic mood disorders for approximately 2.3 million patients worldwide. Considering the increase in olanzapine prescriptions and the increased risk of suicide in this patient population, the number of reported cases of olanzapine overdose may be expected to increase. This report describes the clinical course and serum concentrations in a patient who consumed an olanzapine overdose (800 mg). Profound central nervous system depression and tachycardia without arrhythmia occurred within 2 hours after the ingestion. Additional clinical findings (ie, fever, mutism, agitation, dystonia, akathisia, elevated creatine kinase, and increased leukocyte count) were similar to those of neuroleptic malignant syndrome. After intubation, gut decontamination, and supportive care, the patient recovered and was discharged.

Adult↗
PubMed1999

Use of partial liquid ventilation to manage pulmonary complications of acute verapamil-sustained release poisoning.

INTRODUCTION: Verapamil is a papaverine-derived calcium channel blocker widely used for the treatment of hypertension and supraventricular tachyarrhythmias. It is one of the leading agents involved in pharmaceutical poisoning-related deaths among adults. CASE REPORT: We report a case of severe sustained-release verapamil poisoning associated with respiratory failure in an adult man who survived after receiving 4 days of partial liquid ventilation as a part of his medical management.

Adult↗
PubMed1998

Amiloride analogs inhibit chronic hypoxic pulmonary hypertension.

Na+/H+ exchange regulation of intracellular pH may play a permissive role in pulmonary artery smooth muscle cell (PASM) proliferation. Our laboratory has demonstrated that dimethyl amiloride (DMA), an amiloride derivative with enhanced selectivity as an inhibitor of the Na+/H+ antiporter, can inhibit bovine PASM proliferation in vitro. We hypothesized that DMA would inhibit development of hypoxic pulmonary hypertension by interfering with PASM growth in vivo. Sprague-Dawley rats were exposed to 10% O2 for 14 d without (n 9) or with (n = 7) DMA continuous infusion 3 mg/ kg/d. The animals treated with DMA had significant reductions in pulmonary artery pressure and total pulmonary vascular resistance index (TPVRI) when compared with hypoxic control rats (p < 0.05). Pulmonary vascular remodeling was significantly reduced in animals treated with DMA as measured by percent wall thickness and percentage of thick-walled intra-acinous vessels (p < 0.05). We used a second Na+/H+ exchange inhibitor, ethylisopropyl amiloride (EIPA, 3 mg/kg/d, n = 9), and found similar reductions in pulmonary artery pressure, TPVRI, and pulmonary vascular remodeling. Polycythemia during hypoxia was unchanged by treatment with DMA or EIPA. In conclusion, despite the hypertensive effects of polycythemia, DMA and EIPA can significantly reduce pulmonary vascular remodeling induced by chronic hypoxia.

Amiloride↗
PubMed1997

Influence of molecular weight, protein core and charge of native heparin fractions on pulmonary artery smooth muscle cell proliferation.

Heparin macromolecules have been shown to inhibit cultured pulmonary artery smooth muscle cell proliferation in vitro and prevent hypoxic vascular remodeling in vivo. In an attempt to understand the structural determinants of heparin's antiproliferative properties, we have fractionated an antiproliferative preparation of commercial heparin into low and high molecular weight fractions. Then the high molecular weight heparin fraction was further fractionated on a DEAE-cellulose column by charge density eluting with 0 - 1 M NaCl linear gradient. The heparin protein peptides were both removed and isolated. These heparin fractions were assayed for antiproliferative effects on cultured bovine pulmonary artery smooth muscle cells. No appreciable differences were found among high and low molecular weight heparin fractions The core peptides showed no antiproliferative activity. However, higher charge density fraction was less antiproliferative.

Analysis of Variance↗
PubMed1996

Antiproliferative role of 3-O-sulfate glucosamine in heparin on cultured pulmonary artery smooth muscle cells.

Heparin macromolecules inhibit vascular remodeling associated with hypoxic pulmonary hypertension. Heparin's antiproliferative effect on smooth muscle cells, based on studies of synthetic pentasaccharide fragments, has been attributed to 3-O-sulfate on the internal glucosamine. To determine the role of 3-O-sulfation in smooth muscle cell growth, we treated three heparins of varying potency with heparitinases I and II, which degrade heparin fragments containing 3-O-sulfate on the glucosamine residue to delta-tetrasaccharides only. Our most antiproliferative heparin gave the least amount of delta-tetrasaccharides. This heparin was then fractionated according to degree of sulfation using ETOH precipitation. Again we found no antiproliferative difference between the highly sulfated fractions and those with a lesser degree of sulfation. These studies suggest that 3-O-sulfate of glucosamine residue is not critical in whole heparins for antiproliferative activity.

Animals↗
PubMed1996

Differential effect of three commercial heparins on Na+/H+ exchange and growth of PASMC.

Heparin preparations vary in chemical content and in antiproliferative activity for pulmonary artery smooth muscle cells (PASMC). Intracellular alkalinization via stimulation of the Na+/H+ antiporter appears to be a permissive event for proliferation of PASMC. We wondered whether the variable effect of heparin preparations on PASMC growth might be due to different degrees of inhibition of the Na+/H+ antiporter and whether variations in chemical formulation might correlate with the inhibition. Fluorescent microscopy of bovine PASMC was done using a dye with which fluorescence varies directly with intracellular pH (pHi). Bovine PASMC were preincubated with three heparin preparations previously shown to vary in antiproliferative activity, at 1.0 microgram/ml for 24 h. Platelet-derived growth factor (PDGF; 60 ng/ml) on PASMC without heparin resulted in a rise in pHi of 0.27 +/- 0.02 pH units. The rise in pH units in heparin-treated PASMC was 0.34 +/- 0.03 with Choay, 0.21 +/- 0.02 with Elkins-Sinn, and 0.07 +/- 0.02 with Upjohn (+/-SE; all P < 0.05; n = 5). Upjohn heparin incubation for as little as 15 min still impeded the rise in pH induced by PDGF. Heparin did not block the Na+/H+ exchanger directly, as it still restored pHi in response to an acid load. Compared with PASMC proliferation induced by 60 ng/ml PDGF, 1 microgram/ml of Choay, Elkins-Sinn, and Upjohn heparin produced -4 +/- 7.4, 1.4 +/- 4.8, and 48 +/- 2.2% inhibition of PDGF control, respectively (P < 0.05 for Upjohn compared with PDGF and Choay). The heparins varied in protein content and amino acid composition. However, amino acid and glucosamine composition, total sulfation, and extent of 3-O-sulfation did not predict their activity. Thus inhibition of PDGF activation of the Na+/H+ antiporter by a given heparin preparation correlated well with its ability to inhibit PASMC proliferation.

Animals↗
PubMed1996

The role of Na+/H+ exchange and growth factors in pulmonary artery smooth muscle cell proliferation.

Chronic hypoxia produces pulmonary hypertension, in part because of hypertrophy and hyperplasia of pulmonary artery smooth muscle cells (PA SMC). Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) have been shown to stimulate SMC proliferation and may be involved in these vascular changes. Both factors cause a rise in intracellular pH (pHi) in systemic vascular SMC through stimulation of the Na+/H+ exchanger, an event that has been thought to be permissive, allowing cell proliferation in response to the growth factor. The present studies examined the possibility that the activation of Na+/H+ exchange is involved in the PA SMC mitogenic response to these growth factors. Na+/H+ exchange activity was assessed by monitoring pHi in cultured cells using the pH-sensitive dye, 2'7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). PDGF (60 ng/ml) exposure led to a marked activation of Na+/H+ exchange, evidenced by a rise in pHi (mean +/- SEM) of 0.20 +/- 0.03 pH units (n = 5, P < 0.05). EGF (60 ng/ml) exposure produced a rise in pHi of 0.27 +/- 0.03 pH units (n = 5, P < 0.05). Dimethyl amiloride (DMA, 50 microM), a competitive inhibitor of Na+/H+ exchange, blocked the pH response to PDGF and EGF. PA SMC showed a proliferative response when exposed to PDGF and EGF which was attenuated by 50 microM DMA (n = 6). Thus, activation of the Na+/H+ exchanger may be important in pulmonary cell signaling in response to growth factors as it has been found to be in systemic vessels.

Alkalies↗
PubMed1995

Bronchoalveolar lavage fluid phospholipase A2 activities are increased in human adult respiratory distress syndrome.

The role of phospholipase A2 (PLA2) in lung injury in humans is unclear. Previous studies have failed to identify an increase in PLA2 activity in bronchoalveolar lavage fluids (BALF) of patients with the adult respiratory distress syndrome (ARDS). In this study, increased phospholipase A2 (PLA2) activity was detected in BALF from patients with ARDS. PLA2 levels in BALF correlated positively with lung injury score in patients with lung disease. BALF PLA2 activity in patients with ARDS was resolved into heparin binding and nonbinding activities. Both PLA2 activities were increased in BALF of ARDS patients. The PLA2 activity that bound to heparin was identified as a group II PLA2 by its chromatographic characteristics, its inhibition by dithiothreitol, its substrate specificity, and its approximate molecular mass of 14 kDa. The second PLA2 activity was further purified and found to require Ca2+ at a concentration > 2 x 10(-4) M for activity. This form of PLA2 exhibited a neutral and broad pH optimum (pH 6.0-8.0) and hydrolyzed both phosphatidylethanolamine and phosphatidylcholine effectively. Its apparent molecular mass was estimated to be 80-90 kDa. Neither anti-pancreatic PLA2 antiserum nor anti-pig spleen cytosolic 100-kDa PLA2 antiserum immunoprecipitated the enzymatic activity. Thus at least two forms of PLA2 are increased in activity in BALF of patients with ARDS, a group II PLA2 and a biochemically and immunochemically form distinct from group I, group II, and cytosolic PLA2. Increased lung PLA2 activity may be important for the pathophysiology of ARDS.

Adult↗
PubMed1995

Na+/H+ exchange in pulmonary artery smooth muscle from spontaneously hypertensive and Wistar-Kyoto rats.

Na+/H+ exchanger regulation of intracellular pH (pHi) may play a key permissive role in the mitogen-induced vascular smooth muscle cell growth that occurs in systemic and pulmonary vascular remodeling. Spontaneously hypertensive rats (SHR) have increased Na+/H+ exchange in systemic vessels as well as greater systemic vascular remodeling compared with normotensive Wistar-Kyoto rats (WKY). In contrast to WKY, SHR demonstrate only mild pulmonary hypertension and no increased remodeling to hypoxia compared with WKY. We therefore wondered whether Na+/H+ exchange in pulmonary artery smooth muscle (PASM) of SHR might not be elevated compared with WKY. Baseline pHi, Vmax, pK0.5, and Hill coefficient were compared in 12- to 14-wk-old SHR and WKY PASM and aortic smooth muscle (AoSM) segments by ratio fluorescence spectroscopy. The Vmax, pK0.5, and Hill coefficient were significantly increased in SHR AoSM segments compared with WKY AoSM segments (53, 0.55, and 53%, respectively; P < 0.05). There were no differences in these values between SHR and WKY PASM segments, unlike the AoSM segments. We conclude that the Na+/H+ exchanger activity in PASM in the SHR is the same as in the WKY, which is in contrast to systemic arteries where Na+/H+ exchange is greater in the SHR.

Amiloride↗
PubMed1994

Hemodynamic effects of inhaled nitric oxide in heart failure.

OBJECTIVES: This study was performed to assess the utility of inhaled nitric oxide as a selective pulmonary vasodilator in patients with severe chronic heart failure and to compare its hemodynamic effects with those of nitroprusside, a nonselective vasodilator. BACKGROUND: Preoperative pulmonary vascular resistance is a predictor of right heart failure after heart transplantation. Non-selective vasodilators administered preoperatively to assess the reversibility of pulmonary vasoconstriction cause systemic hypotension, limiting their utility. METHODS: Systemic and pulmonary hemodynamic measurement were made at baseline, during oxygen inhalation and with the addition of graded doses of inhaled nitric oxide or intravenous nitroprusside in 16 patients with New York Heart Association class III or IV heart failure referred for heart transplantation. RESULTS: Pulmonary vascular resistance decreased to a greater extent with 80 ppm nitric oxide (mean +/- SEM 256 +/- 41 to 139 +/- 14 dynes.s.cm-5) than with the maximally tolerated dose of nitroprusside (264 +/- 49 to 169 +/- 30 dynes.s.cm-5, p < 0.05, nitric oxide vs. nitroprusside). Pulmonary capillary wedge pressure increased with 80 ppm nitric oxide (26 +/- 2 to 32 +/- 2 mm Hg, p < 0.05). Mean arterial pressure did not change with nitric oxide but decreased with nitroprusside. Seven of the 16 patients, including 1 patient who did not have an adequate decrease in pulmonary vascular resistance with nitroprusside but did with nitric oxide, have undergone successful heart transplantation. CONCLUSIONS: Inhaled nitric oxide is a selective pulmonary vasodilator in patients with pulmonary hypertension due to left heart failure and may identify patients with reversible pulmonary vasoconstriction in whom agents such as nitroprusside cause systemic hypotension. Inhaled nitric oxide causes an increase in left ventricular filling pressure by an unknown mechanism.

Administration, Inhalation↗
PubMed1994

Functional and structural changes with hypoxia in pulmonary circulation of spontaneously hypertensive rats.

Chronic hypoxic pulmonary hypertension involves both vasoconstriction and vascular remodeling. Spontaneously hypertensive rats (SHR) have an increased systemic vascular resistance and a greater responsiveness to constricting stimuli. We hypothesized that, in contrast to age-matched normotensive Wistar-Kyoto rats (WKY), SHR also display spontaneous pulmonary hypertension in normoxia and increased vascular response to acute and chronic hypoxia. Baseline mean pulmonary arterial pressure (PAP) and total pulmonary resistance (TPR) were higher in SHR than in WKY. With acute hypoxia (10% O2 for 15 min), PAP increased to the same extent in SHR and WKY and cardiac output (CO) was unchanged in WKY but increased in SHR. Thus, the rise in PAP in the SHR might be accounted for by the rise in CO, as TPR did not rise, but not that in the WKY, as TPR increased. After 12 days in hypoxia (10% O2), mean arterial pressure was unchanged in WKY but decreased significantly in SHR without a change in CO. PAP increased by 59% in SHR and 54% in WKY when the rats were taken from the hypoxic chamber for 1 h. Acute hypoxic challenge caused a further increase in PAP only in WKY. Medial wall thickness of alveolar duct and terminal bronchial vessels was similar in WKY and SHR after chronic hypoxia. We conclude that SHR exhibit mild baseline pulmonary hypertension in normoxia and that chronic hypoxia does not produce a disproportionate increase in SHR pulmonary vascular remodeling and pulmonary hypertension.

Animals↗