Biomedical subjects

G Marshall

Publications and source records attributed to G Marshall.

At least 19 recordsLinked to original sources

PubMed2004

Phytoestrogens possess a weak antioxidant activity on low density lipoprotein in contrast to the flavonoid quercetin in vitro in postmenopausal women.

BACKGROUND: Phytoestrogens are a family of plant-derived compounds with weak estrogenic and antiestrogenic properties. The antioxidant capacity of phytoestrogens has been proposed as one of the important mechanisms that explain their health benefits. OBJECTIVE: To determine the in vitro potency of three phytoestrogens, ubiquitous in food, (biochanin A, daidzein and genistein) as antioxidants of low density lipoprotein (LDL) and to compare them with the well-established antioxidant actions of estradiol and quercetin, an ubiquitous flavonoid which is found in high concentration in onions, tea and berries. METHODS: LDL was isolated by ultracentrifugation from the plasma of ten healthy postmenopausal women who were not on hormone therapy. Aliquots containing 0.5 mg of protein were incubated for 4 h with CuSO4 15 micromol/l to induce oxidative stress and with one of the five compounds studied: estradiol, quercetin, biochanin A, daidzein, and genistein, in doses of 0, 5, 15, 50, 500, 1000 and 2000 micromol/l. In addition, we studied the combined effect of estradiol 1 micromol/l plus quercetin 1 micromol/l, comparing their antioxidant action with that of each compound separately. Malonaldehyde (MDE nmol/ mg protein) was measured as a marker of LDL oxidation. RESULTS: Estradiol and quercetin induced a dose-dependent decrease in MDE concentration (p < 0.01). Comparing the areas under the curve, the antioxidant effect of quercetin was 8 times higher than the one observed with estradiol (p < 0.01). A 50% decrease in MDE was reached by quercetin at a concentration of 3.4 micromol/l, estradiol at 29 micromol/l, genistein at 280 micromol/l, biochanin at 1312 mmol/l and daidzein at 8007 mmol/l. Estradiol 1 micromol/l and quercetin 1 micromol/l did not modify MDE generation separately, but, when incubated combined, there was a significant decrease of MDE (p < 0.02). CONCLUSION: The phytoestrogens studied showed a weak antioxidant activity in vitro. The flavonoid quercetin, in contrast, showed the most potent antioxidant activity in vitro, higher than estradiol. Estradiol and quercetin showed additive antioxidant activity. We speculate that different compounds with variable antioxidant effects could amplify their antioxidant capacity when acting combined.

Antioxidants↗

PubMed2003

Three-dimensional nature of ion transport in thin-layer electrodeposition.

A generalized three-dimensional model for ion transport in electrodeposition is introduced. Ion transport is mainly governed by diffusion, migration, and convection. When convection prevails, in particular, in the limiting case of gravity-driven convection, the model predicts concentration shells and convection rolls and their interaction mode with a deposit tip: shell and roll bend and surround the tip forming a three-dimensional envelope tube squeezed at the deposit tip. In the limiting case of electrically driven convection, a vortex ring and an electric spherical drop crowning the deposit tip are predicted. When gravity and electric convection are both relevant, the interaction of ramified deposits, vortex tubes and rings, and electric spherical drops, leading to complex helicoidal flow, is predicted. Many of these predictions are experimentally observed, suggesting that ion transport underlying dendrite growth is remarkably well captured by our model.

Animals↗

PubMed2003

Regional heterothermy and conservation of core temperature in emperor penguins diving under sea ice.

Temperatures were recorded at several body sites in emperor penguins (Aptenodytes forsteri) diving at an isolated dive hole in order to document temperature profiles during diving and to evaluate the role of hypothermia in this well-studied model of penguin diving physiology. Grand mean temperatures (+/-S.E.) in central body sites during dives were: stomach: 37.1+/-0.2 degrees C (n=101 dives in five birds), pectoral muscle: 37.8+/-0.1 degrees C (n=71 dives in three birds) and axillary/brachial veins: 37.9+/-0.1 degrees C (n=97 dives in three birds). Mean diving temperature and duration correlated negatively at only one site in one bird (femoral vein, r=-0.59, P<0.05; range <1 degrees C). In contrast, grand mean temperatures in the wing vein, foot vein and lumbar subcutaneous tissue during dives were 7.6+/-0.7 degrees C (n=157 dives in three birds), 20.2+/-1.2 degrees C (n=69 in three birds) and 35.2+/-0.2 degrees C (n=261 in six birds), respectively. Mean limb temperature during dives negatively correlated with diving duration in all six birds (r=-0.29 to -0.60, P<0.05). In two of six birds, mean diving subcutaneous temperature negatively correlated with diving duration (r=-0.49 and -0.78, P<0.05). Sub-feather temperatures decreased from 31 to 35 degrees C during rest periods to a grand mean of 15.0+/-0.7 degrees C during 68 dives of three birds; mean diving temperature and duration correlated negatively in one bird (r=-0.42, P<0.05). In general, pectoral, deep venous and even stomach temperatures during diving reflected previously measured vena caval temperatures of 37-39 degrees C more closely than the anterior abdominal temperatures (19-30 degrees C) recently recorded in diving emperors. Although prey ingestion can result in cooling in the stomach, these findings and the lack of negative correlations between internal temperatures and diving duration do not support a role for hypothermia-induced metabolic suppression of the abdominal organs as a mechanism of extension of aerobic dive time in emperor penguins diving at the isolated dive hole. Such high temperatures within the body and the observed decreases in limb, anterior abdomen, subcutaneous and sub-feather temperatures are consistent with preservation of core temperature and cooling of an outer body shell secondary to peripheral vasoconstriction, decreased insulation of the feather layer, and conductive/convective heat loss to the water environment during the diving of these emperor penguins.

Animals↗

PubMed2003

Mediterranean diet, but not red wine, is associated with beneficial changes in primary haemostasis.

OBJECTIVE: (1) To compare the effect of an alcohol-free Mediterranean-type diet (MD) and a high-fat diet (HFD) on variables of primary haemostasis (bleeding time, plasma von Willebrand factor and platelet aggregation/secretion). (2) To test whether red wine supplementation modified these variables, independently of the diet. DESIGN, SUBJECTS AND INTERVENTION: Controlled prospective intervention study. Two groups, each consisting of 21 healthy male university students (22+/-3.4 y), received either MD or HFD during 90 days. Between days 30 and 60, both diets were supplemented with 240 ml/day of red wine. Baseline (T0) and T30, T60 and T90-day samples were drawn. Bleeding time was measured before (day 30) and after (day 60) wine supplementation. No drop out from the study was experienced. SETTING: University campus and outpatient nutrition clinic. RESULTS: All baseline (day 0) variables did not differ significantly between study groups. On day 30, individuals on MD had significantly higher levels of plasma beta-carotene, folate, ascorbate, and eicosapentaenoic acid in plasma lipid fractions, than those on HFD. Total plasma cholesterol, HDL and LDL did not change significantly in either study group at any time point. After 30 days on each diet, individuals on MD had longer bleeding time (BT) than those on HFD (7.6+/-2.8 vs 5.8+/-1.7 min; P=0.017). BT did not change significantly after I month of wine supplementation (7.1+/-2.0 vs 5.5+/-2.0 min, respectively). Plasma von Willebrand factor (vWF : Ag) on day 0 was 89+/-40 and 111+/-70% in MD and HFD groups, respectively (P=0.21). These values did not change significantly at 30, 60 or 90 days. MD intake was associated with an increase in platelet serotonin secretion (P=0.02) and a marginal increase in platelet aggregation after stimulation with epinephrine (P=0.07). Wine intake resulted in a marginal decrease in platelet (14)C-5-HT secretion with 4 micro M ADP (P=0.07). However, both platelet aggregation and secretion were consistently increased when using collagen as agonist (1 and 2 micro g/ml, P=0.01). CONCLUSION: The longer BT in individuals on MD, obtained independently of red wine, denotes less interaction of platelets with the vascular wall, which could be beneficial from the point of view of cardiovascular (CV) risk. This effect is not explained by changes in the measured haemostatic determinants of BT (plasma vWF, ex vivo platelet function), and might be attributed to other as yet unknown vascular factors. Moderate consumption of red wine results in a significant increase in ex vivo platelet aggregation and secretion after stimulation with collagen. This observation contradicts previous reports, although further studies are required to elucidate the influence of this finding on CV risk.

Adult↗

PubMed2002

Transition from gravito- to electroconvective regimes in thin-layer electrodeposition.

The transition from gravitoconvective to electroconvective prevailing regimes in thin-layer electrochemical deposition is analyzed through variations of electrolyte viscosity at constant cell thickness. The distribution of velocity directions at the deposit front is a measure of the relative weight of electroconvection versus gravitoconvection, and a signature of that transition. The experiments are carried out under galvanostatic conditions in convection prevailing regimes. Particle image velocimetry reveals that at low viscosities, buoyancy driven convection dominates; as viscosity increases, electrically driven convection becomes more important, eventually prevailing. The transition is observed at 1.5 times the viscosity of water. The theoretical model presented reveals that an increase of the Poisson and Reynolds numbers and a decrease of the Peclet and electric Grashof numbers, when viscosity increases, makes the electroconvective motion relatively more important. The model predicts a transition at approximately two times the viscosity of water. We may conclude that, in a physicochemical hydrodynamic flow involving ions, under galvanostatic conditions, increasing viscosity damps gravitoconvection and enhances electroconvection.

Journal Article↗

PubMed2002

Single-dose pharmacokinetics and penetration of BMS 284756 into an inflammatory exudate.

The pharmacokinetics of a single dose of BMS 284756 were determined following oral administration of a 600-mg dose to eight healthy male volunteers. Concentrations of the drug were measured in plasma and a cantharidine-induced inflammatory exudate by a microbiological assay. The mean peak concentration in plasma of 10.4 microg/ml (standard deviation [SD], 1.3 microg/ml) was attained at a mean time of 1.2 h (SD, 0.5 h) after the dose. The penetration into the inflammatory exudate was 82% (SD, 15.7%). A mean peak concentration of 7.2 microg/ml (SD, 2.4 microg/ml) was attained in the inflammatory exudate at 5.3 h (SD, 1.5 h). The elimination half-lives from plasma and inflammatory fluid were 9.8 h (SD, 1.1 h) and 8.5 h (SD, 1.9 h), respectively. The areas under the concentration-time curves for plasma and inflammatory fluid were 96.7 microg x h/ml (SD, 10.3 microg x h/ml) and 77.9 microg x h/ml (SD, 19.2 microg x h/ml), respectively.

Adult↗

PubMed2002

Pharmacokinetics and inflammatory fluid penetration of intravenous daptomycin in volunteers.

The lipopeptide antimicrobial daptomycin was administered intravenously at a dose of 4 mg/kg of body weight to seven healthy male volunteers. The concentrations of daptomycin in plasma, cantharidin-induced inflammatory fluid, and urine were measured by a microbiological assay. The mean +/- standard deviation peak concentrations in plasma and inflammatory fluid were 77.5 +/- 8.3 and 27.6 +/- 9.5 microg/ml, respectively; the mean terminal elimination half-lives were 7.74 and 13.2 h, respectively. The overall penetration of total drug into the inflammatory fluid (measured by ratio of the area under the concentration-time curve from 0 to 24 h for inflammatory fluid compared with that for plasma) was 68.4%. The mean urinary recovery over 24 h was 59.7%.

Adult↗

PubMed2002

Stroke frequencies of emperor penguins diving under sea ice.

During diving, intermittent swim stroke patterns, ranging from burst/coast locomotion to prolonged gliding, represent potential energy conservation mechanisms that could extend the duration of aerobic metabolism and, hence, increase the aerobic dive limit (ADL, dive duration associated with onset of lactate accumulation). A 5.6 min ADL for emperor penguins had been previously determined with lactate measurements after dives of <50 m depth. In order to assess locomotory patterns during such dives, longitudinal acceleration was measured with an attached accelerometer in 44 dives of seven adult birds diving from an isolated dive hole in the sea ice of McMurdo Sound, Antarctica. Detection of wing strokes in processed accelerometer data was verified in selected birds with analysis of simultaneous Crittercam underwater video footage. Mean dive duration of birds equipped with the accelerometer and a time-depth recorder (TDR) was 5.7+/-2.2 min; 48% of these dives were greater than the measured 5.6 min ADL (ADL(M)). Highest stroke frequencies (0.92+/-0.31 Hz, N=981) occurred during the initial descent to 12 m depth. Swimming effort was reduced to a mean stroke frequency <0.70 Hz during other phases of the dive (while traveling below 12 m depth, during foraging ascents/descents to and from the sub-ice surface, and during final ascents to exit). The longest stroke interval (8.6 s) occurred during a feeding excursion to the undersurface of the ice. In dives >ADL(M), mean stroke frequency during travel segments was significantly less than that in dives 10 s) periods of prolonged gliding during these shallow (<60 m) foraging dives. However, a stroke/glide pattern was evident with more than 50% of strokes associated with a stroke interval >1.6 s, and with lower stroke frequency associated with increased dive duration.

Animals↗

PubMed2001

Growth factors regulate the survival and fate of cells derived from human neurospheres.

Cells isolated from the embryonic, neonatal, and adult rodent central nervous system divide in response to epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF-2), while retaining the ability to differentiate into neurons and glia. These cultures can be grown in aggregates termed neurospheres, which contain a heterogeneous mix of both multipotent stem cells and more restricted progenitor populations. Neurospheres can also be generated from the embryonic human brain and in some cases have been expanded for extended periods of time in culture. However, the mechanisms controlling the number of neurons generated from human neurospheres are poorly understood. Here we show that maintaining cell-cell contact during the differentiation stage, in combination with growth factor administration, can increase the number of neurons generated under serum-free conditions from 8% to > 60%. Neurotrophic factors 3 and 4 (NT3, NT4) and platelet-derived growth factor (PDGF) were the most potent, and acted by increasing neuronal survival rather than inducing neuronal phenotype. Following differentiation, the neurons could survive dissociation and either replating or transplantation into the adult rat brain. This experimental system provides a practically limitless supply of enriched, non-genetically transformed neurons. These should be useful for both neuroactive drug screening in vitro and possibly cell therapy for neurodegenerative diseases.

Animals↗

PubMed2001

Complementary effects of Mediterranean diet and moderate red wine intake on haemostatic cardiovascular risk factors.

OBJECTIVES: To compare the effect of alcohol-free Mediterranean-type diet (MD) and high-fat diet (HFD) on plasma concentration of emergent haemostatic cardiovascular risk factors (HCVRF). Also, to test if red wine supplementation modifies HCVRF, independent of diet. DESIGN, SUBJECTS AND INTERVENTION: Controlled prospective intervention study. Two groups, each of 21 healthy male university students (22+/-3.4 y), received either MD or HFD for 90 days. Between days 30 and 60, both diets were supplemented with 240 ml/day of red wine. Baseline and T30, T60 and T90-day samples were drawn. No drop out from the study was observed. SETTING: University campus and outpatient nutrition clinic. RESULTS: Volunteers on HFD at T30 had increases in pro-coagulants fibrinogen (22%), factor VIIc (9%), and factor VIIIc (4%), and decreases in natural anticoagulants antithrombin III (3%), protein C (11%) and protein S (6%) and of 20% in plasminogen activator inhibitor-1. At the same time, individuals on MD had increases in fibrinogen (4%), antithrombin III (5%), protein C (3%), protein S (2.7%), and decreases in factor VIIIc (9%), and plasminogen activator inhibitor-1 (21%). After adjusting by baseline values, MD was associated with lower plasma fibrinogen (P=0.03), factor VIIc (P=0.034) and factor VIIIc (P=0.0057) and with higher levels of protein S (P=0.013). Red wine supplementation, in both diets, resulted in decreased plasma fibrinogen (P=0.001) and factor VIIc (P=0.05), and increased tissue plasminogen activator antigen (P=0.01) and plasminogen activator inhibitor-1 antigen (P=0.0003). Wine consumption was also associated with significantly (P=0.01) divergent effects on antithrombin III: it decreased by 10% in individuals on HFD but increased slightly in those on MD. No effects of diet or wine were detected in plasma protein C and C-reactive protein. CONCLUSION: MD and moderate consumption of red wine have complementary, mostly beneficial effects on HCVRF.

Adult↗

PubMed2001

Increased activation of protein C, but lower plasma levels of free, activated protein C in uraemic patients: relationship with systemic inflammation and haemostatic activation.

Chronic renal failure (CRF) courses with both systemic inflammatory reaction and haemostatic activation. We explored the relationship of these processes with plasma levels of free, activated protein C (APC) and complexes of APC with its inhibitors in patients with CRF under conservative treatment. Plasma concentrations of inflammatory cytokines [tumour necrosis factor alpha (TNFalpha) and interleukin 8], acute-phase proteins (C-reactive protein, fibrinogen, alpha1-anti-trypsin and von Willebrand factor), and markers of haemostatic activation (thrombin-anti-thrombin complexes, plasmin-anti-plasmin complexes, and fibrin and fibrinogen degradation products) were higher in patients than in controls. Inflammatory and haemostatic markers were significantly and positively correlated. Total plasma APC and APC:alpha1-anti-trypsin (alpha1AT) complexes were 44% and 75% higher in patients than in controls (P = 0.0001), whereas free APC was 20% lower (P < 0.015). No significant difference was observed in APC:protein C inhibitor (PCI) complexes between both groups. The free/total APC ratio was significantly lower in patients than in controls (P < 0.0001). Total plasma APC and APC:alpha1AT were positively correlated with activation markers of haemostasis and acute-phase proteins, whereas free APC was inversely correlated with plasma levels of creatinine, acute-phase proteins and fibrin degradation products (FnDP). Systemic inflammation and activation of haemostasis are interrelated processes in CRF. APC generation was increased in response to elevated thrombin production, but the inflammatory reaction, associated with increased synthesis of alpha1AT, reduced its anticoagulant effect. Lower free plasma APC in CRF may be pathogenically associated with atherothrombosis, a major cause of death in this disease.

Adult↗

PubMed2001

Immune responsiveness following academic stress in first-year medical students.

Many studies illustrate that physical or psychologic stressors can alter human immune function, which might predispose one to an increased susceptibility to infections. In the present study, we monitored immune responsiveness in 16 first-year medical students (age 23.8 +/- 2.2 years) during the first examination session. Baseline blood samples were collected 30 days prior to the first examination session. Subsequently, subjects were randomly assigned to two groups, and blood samples were collected at 24 h (POST24h) or 48 h (POST48h) after an examination. The percentage of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD3(+)CD45RO(+), CD3(+)CD45RA(+), CD3(-)CD16(+)56(+), CD19(+), and CD14(+) cells in whole blood was examined to determine changes in circulating immune cell populations. Activation of peripheral blood mononuclear cells (PBMC) with a mixture of phorbol myristate acetate (PMA) and ionomycin or lipopolysaccharide (LPS) for 4 h was used to assess the distribution of interleukin-2 (IL-2)-secreting or interferon-gamma (IFN-gamma)-secreting CD4(+) and CD8(+) cells, as well as IL-1alpha-secreting CD14(+) cells. Activation with a combination of phytohemagglutinin (PHA) and LPS was used to assess secretion of IL-2, IFN-gamma, IL-4, IL-10, soluble IL-2 receptor-alpha (sIL-2Ralpha), IL-1beta, and IL-1R antagonist (IL-1Ra) by PBMC in 48-h cell culture. A significantly higher level of total T cells was found at POST24h, and CD14(+) was elevated at both POST24h and POST48h. The percentage of CD4(+) and CD8(+) cells significantly declined at POST24 and POST48h. A significant elevation in the percentage of memory T cells was observed at POST48h, whereas the percentage of naive T cells was elevated at POST24h and POST48h. These changes were accompanied by a significant decline in percentage of natural killer (NK) cells 24 h after the examination. The percentage of IL-2-producing CD4(+) and CD8(+) cells was significantly lower at POST24h, and the percentage of CD8(+)IFN-gamma(+) cells significantly declined at POST48h. The percentage of CD14(+)IL-1alpha(+) significantly declined at both POST24 and POST48h. A significant decrease was observed in IL-2 secretion 24 h after the examinations, and the secretion of IL-4 and IL-1beta significantly declined at POST48h. No changes in IFN-gamma, IL-10, sIL-2Ralpha, and IL-1Ra secretion were observed. We conclude that the stress outcomes of academic examinations in first-year medical students can significantly alter immune cell distribution and in vitro production and secretion of specific cytokines.

Adult↗

PubMed2001

Pharmacokinetics and tissue penetration of gemifloxacin following a single oral dose.

The pharmacokinetics and tissue penetration of gemifloxacin were determined during a 24 h period following oral administration of a single 320 mg dose to each of 10 healthy male volunteers. Concentrations of the drug in plasma, inflammatory blister fluid and urine were determined using a microbial assay. A peak plasma concentration (mean +/- S.D.) of 2.33 +/- 0.5 mg/L was reached at 1.20 +/- 0.4 h. Mean penetration into inflammatory fluid was 61.19 +/- 10.4%. A peak concentration of 0.74 +/- 0.3 mg/L was reached in the inflammatory fluid at a mean time of 3.40 +/- 1.7 h. The mean elimination half-life from serum and inflammatory fluid was 5.94 +/- 0.4 and 6.27 +/- 2.4 h, respectively. Urinary excretion of the drug at 24 h post-dose was 36.11% of the total given. These results demonstrate that gemifloxacin penetrates into the site of inflammation and reaches sufficient concentrations to inhibit many pathogens.

Administration, Oral↗

PubMed2001

Effect of alpha subunit on allosteric modulation of ion channel function in stably expressed human recombinant gamma-aminobutyric acid(A) receptors determined using (36)Cl ion flux.

Inhibitory gamma-aminobutyric acid (GABA)(A) receptors are subject to modulation at a variety of allosteric sites, with pharmacology dependent on receptor subunit combination. The influence of different alpha subunits in combination with beta3gamma2s was examined in stably expressed human recombinant GABA(A) receptors by measuring (36)Cl influx through the ion channel pore. Muscimol and GABA exhibited similar maximal efficacy at each receptor subtype, although muscimol was more potent, with responses blocked by picrotoxin and bicuculline. Receptors containing the alpha3 subunit exhibited slightly lower potency. The comparative pharmacology of a range of benzodiazepine site ligands was examined, revealing a range of intrinsic efficacies at different receptor subtypes. Of the diazepam-sensitive GABA(A) receptors (alpha1, alpha2, alpha3, alpha5), alpha5 showed the most divergence, being discriminated by zolpidem in terms of very low affinity, and CL218,872 and CGS9895 with different efficacies. Benzodiazepine potentiation at alpha3beta3gamma2s with nonselective agonist chlordiazepoxide was greater than at alpha1, alpha2, or alpha5 (P < 0.001). The presence of an alpha4 subunit conferred a unique pharmacological profile. The partial agonist bretazenil was the most efficacious benzodiazepine, despite lower alpha4 affinity, and FG8205 displayed similar efficacy. Most striking were the lack of affinity/efficacy for classical benzodiazepines and the relatively high efficacy of Ro15-1788 (53 +/- 12%), CGS8216 (56 +/- 6%), CGS9895 (65 +/- 6%), and the weak partial inverse agonist Ro15-4513 (87 +/- 5%). Each receptor subtype was modulated by pentobarbital, loreclezole, and 5alpha-pregnan-3alpha-ol-20-one, but the type of alpha subunit influenced the level of potentiation. The maximal pentobarbital response was significantly greater at alpha4beta3gamma2s (226 +/- 10% increase in the EC(20) response to GABA) than any other modulator. The rank order of potentiation for pregnanolone was alpha5 > alpha2 > alpha3 = alpha4 > alpha1, for loreclezole alpha1 = alpha2 = alpha3 > alpha5 > alpha4, and for pentobarbital alpha4 = alpha5 = alpha2 > alpha1 = alpha3.

Allosteric Regulation↗

PubMed2001

Pharmacokinetics and tissue penetration of linezolid following multiple oral doses.

The pharmacokinetics of multiple-dose linezolid were determined following administration of five 600-mg oral doses given every 12 h to each of six healthy male volunteers. Concentrations of the drug were determined in plasma and inflammatory blister fluid using high-pressure liquid chromatography. A mean peak concentration in plasma of 18.3 microg/ml (standard deviation [SD], 6.0) was attained at a mean time of 0.7 h (SD, 0.3) after the final dose. The penetration into the inflammatory fluid was 104% (SD, 20.7). A mean peak concentration of 16.4 microg/ml (SD, 10.6) was attained in the inflammatory fluid at 3 h (SD, 0.6) after the final dose. The elimination half-life from serum and inflammatory fluid was 4.9 (SD, 1.8) and 5.7 (SD, 1.7) h, respectively. The area under the concentration-time curve in plasma and blister fluid was 140.3 (SD, 73.1) and 155.3 (SD, 80.1) microg x h/ml, respectively. These data suggest that linezolid has good tissue penetration, and we can predict that it will be successful in the treatment of a variety of gram-positive infections.

Acetamides↗

PubMed2001

Mechanisms of insulin resistance in cystic fibrosis.

Cystic fibrosis (CF) is associated with a high incidence of diabetes. Studies evaluating causes of CF-related diabetes (CFRD) have consistently documented decreased insulin secretion. In patients with CFRD, insulin sensitivity has been documented to be decreased, but controversy exists in patients with normal or impaired glucose tolerance (IGT). We undertook this study 1) to reexplore insulin sensitivity in patients with IGT and 2) to evaluate potential mechanisms of insulin resistance in CF, including GLUT-4 translocation, elevation of serum cytokines, and free fatty acid (FFA) levels. We recruited nine CF subjects with impaired glucose tolerance (IGTCF) and nine age-, gender-, and body mass index-matched control volunteers. Each underwent a hyperinsulinemic euglycemic clamp (200 mU. m(-2). min(-1)) to measure insulin sensitivity. A muscle biopsy was obtained at maximal insulin stimulation for measure of GLUT-4 translocation with sucrose gradients. An oral glucose tolerance test and National Institutes of Health (NIH) clinical status scores were measured in all volunteers. We also measured tumor necrosis factor (TNF)-alpha levels and FFA in all subjects. Additionally, we report the results of TNF-alpha and FFA in 32 CF patients previously studied by our group. Results were that glucose disposal rate (GDR) was significantly lower in the CFIGT subjects than in controls, indicative of impaired insulin action. GLUT-4 translocation was impaired in CF and correlated with GDR. TNF-alpha levels were higher in all CF subjects than in controls and correlated with GDR. There was no difference in FFA between CF and control subjects. Modified NIH clinical status scores were inversely correlated with GDR and TNF-alpha levels. We conclude that IGTCF patients have decreased peripheral insulin sensitivity. Mechanisms include elevation of TNF-alpha and impaired translocation of GLUT-4.

Adult↗

PubMed2001

[Study of cytokines kinetics in severe sepsis and its relationship with mortality and score of organic dysfunction].

BACKGROUND: The Infectious Systemic Inflammatory Response syndrome and multiple organic dysfunction have common physiopathological mechanisms. Multiple organic dysfunction can be assessed using severity scores. AIM: To relate cytokine kinetics with a multiple organic dysfunction score during sepsis. MATERIAL AND METHODS: Tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL6) kinetics were studied in 25 patients with severe sepsis with less than 48 h of evolution and interleukin 1 beta (IL beta) kinetics was studied in 13 patients. Measurements were made at 0, 12, 24 and 48 hours after admission to the study, using an ELISA technique. These parameters were correlated with the Marshall multiple organic dysfunction score and survival. RESULTS: Mean age of study subjects was 70 years, the APACHE II score was 16.9 +/- 6 and the Marshall score was 6.8 +/- 3.6. Sepsis was of pulmonary origin in 56% of patients and intra abdominal in 32%. Mortality was 36%. TNF alpha increased during the study period (24.1 pg/ml initially and 37.8 pg/ml at 24 hours, with a slight posterior reduction, p < 0.02). These levels had no association with mortality or organic dysfunction. IL6 remained elevated during the first hours and had a tendency to decrease thereafter. Decreased patients had higher values than survivors (306 pg/ml and 55.4 pg/ml respectively, p = 0.011). Its values were tightly correlated with Marshall score, with the number of failing organs, with the presence of shock and with probability of dying during hospitalization. IL1 beta remained low and was not associated with clinical parameters. CONCLUSIONS: There is a tight correlation between the elevation of IL6 and the severity of the Systemic Inflammatory Response and mortality in these patients with sepsis.

APACHE↗

PubMed2000

Linear discriminant models for unbalanced longitudinal data.

This paper discusses statistical methods for the classification of observations into one of two or more groups based on longitudinal observations. Measurements on subjects in longitudinal medical studies are often collected at different times and on a different number of occasions. Classical multivariate methods for linear discriminant analysis are difficult to apply to repeated measurements due to the highly unbalanced structure observed in these data. Linear models for the analysis of longitudinal data proposed by Laird and Ware and non-linear models proposed by Lindstrom and Bates can be used to estimate population parameters for a discriminant model that classifies individuals into distinct predefined groups or populations. An example is presented using data from a study in 150 pregnant women in Santiago, Chile, in order to predict normal versus abnormal pregnancy outcomes.

Abortion, Spontaneous↗