Differential effect of pioglitazone (PGZ) and rosiglitazone (RGZ) on postprandial glucose and lipid metabolism in patients with type 2 diabetes mellitus: a prospective, randomized crossover study

Postprandial metabolism is impaired in patients with type 2 diabetes (T2Dm). Two thiazolidinediones pioglitazone (PGZ) and rosiglitazone (RGZ) have similar effects on glycaemic control but differ in their effects on fasting lipids. This study investigated the effects of RGZ and PGZ on postprandial metabolism in a prospective, randomized crossover trial.

SHORT-TERM EFFECTS OF PHENYLEPHRINE ON SYSTEMIC AND REGIONAL HEMODYNAMICS IN PATIENTS WITH SEPTIC SHOCK: A CROSSOVER PILOT STUDY

Clinical studies evaluating the use of phenylephrine in septic shock are lacking. The present study was designed as a prospective, crossover pilot study to compare the effects of norepinephrine (NE) and phenylephrine on systemic and regional hemodynamics in patients with catecholamine-dependent septic shock. In 15 septic shock patients, NE (0.82 +/- 0.69 mug.kg.min) was replaced with phenylephrine (4.39 +/- 5.23 mug.kg.min) titrated to maintain MAP between 65 and 75 mmHg. After 8 h of phenylephrine infusion treatment was switched back to NE. Data from right heart catheterization, acid-base balance, thermo-dye dilution catheter, gastric tonometry, and renal function were obtained before, during, and after replacing NE with phenylephrine. Variables of systemic hemodynamics, global oxygen transport, and acid-base balance remained unchanged after replacing NE with phenylephrine except for a significant decrease in heart rate (phenylephrine, 89 +/- 18 vs. NE, 93 +/- 18 bpm; P < 0.05). However, plasma disappearance rate (phenylephrine, 13.5 +/- 7.1 vs. NE, 16.4 +/- 8.7%.min) and clearance of indocyanine green (phenylephrine, 330 +/- 197 vs. NE, 380 +/- 227mL.min.m), as well as creatinine clearance (phenylephrine, 81.3 +/- 78.4 vs. NE, 94.3 +/- 93.5 mL.min) were significantly decreased by phenylephrine infusion (each P < 0.05). In addition, phenylephrine increased arterial lactate concentrations as compared with NE infusion (1.7 +/- 1.0 vs. 1.4 +/- 1.1 mM; P < 0.05). After switching back to NE, all variables returned to values obtained before phenylephrine infusion except creatinine clearance and gastric tonometry values. Our results suggest that for the same MAP, phenylephrine causes a more pronounced hepatosplanchnic vasoconstriction as compared with NE.

Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus--a prospective single-blinded randomised crossover trial

We assessed systemic and local muscle fuel metabolism during aerobic exercise in patients with type 1 diabetes at euglycaemia and hyperglycaemia with identical insulin levels.

The effect of naloxone-3-glucuronide on colonic transit time in healthy men after acute morphine administration: a placebo-controlled double-blinded crossover preclinical volunteer study

BACKGROUND: Constipation is a significant side effect of opioid therapy. We have previously demonstrated that naloxone-3-glucuronide (NX3G) antagonizes the motility-lowering-effect of morphine in the rat colon. AIM: To find out whether oral NX3G is able to reduce the morphine-induced delay in colonic transit time (CTT) without being absorbed and influencing the analgesic effect. METHODS: Fifteen male volunteers were included. Pharmacokinetics: after oral administration of 0.16 mg/kg NX3G, blood samples were collected over a 6-h period. Pharmacodynamics: NX3G or placebo was then given at the start time and every 4 h thereafter. Morphine (0.05 mg/kg) or placebo was injected s.c. 2 h after starting and thereafter every 6 h for 24 h. CTT was measured over a 48-h period by scintigraphy. Pressure pain threshold tests were performed. RESULTS: Neither NX3G nor naloxone was detected in the venous blood. The slowest transit time was observed during the morphine phase, which was significantly different from morphine with NX3G and placebo. The pain perception was not significantly influenced by NX3G. CONCLUSIONS: Orally administered NX3G is able to reverse the morphine-induced delay of CTT in humans without being detected in peripheral blood samples. Therefore, NX3G may improve symptoms of constipation in-patients using opioid medication without affecting opioid-analgesic effects.

Crossover comparison of the laryngeal mask supreme and the i-gel in simulated difficult airway scenario in anesthetized patients

BACKGROUND: The single-use supraglottic airway devices LMA-Supreme (LMA-S; Laryngeal Mask Company, Henley-on-Thames, United Kingdom) and i-gel (Intersurgical Ltd, Wokingham, Berkshire, United Kingdom) have a second tube for gastric tube insertion. Only the LMA-S has an inflatable cuff. They have the same clinical indications and might be useful for difficult airway management. This prospective, crossover, randomized controlled trial was performed in a simulated difficult airway scenario using an extrication collar limiting mouth opening and neck movement. METHODS: Sixty patients were included. Both devices were placed in random order in each patient. Primary outcome was overall success rate. Other measurements were time to successful ventilation, airway leak pressure, fiberoptic glottic view, and adverse events. RESULTS: Success rate for the LMA-S was 95% versus 93% for the i-gel (P = 1.000). LMA-S needed shorter insertion time (34 +/- 12 s vs. 42 +/- 23 s, P = 0.024). Tidal volumes and airway leak pressure were similar (LMA-S 26 +/- 8 cm H20; i-gel 27 +/- 9 cm H20; P = 0.441). Fiberoptic view through the i-gel showed less epiglottic downfolding. Overall agreement in insertion outcome was 54 (successes) and 1 (failure) or 55 (92%) of 60 patients. The difference in success rate was 1.7% (95% CI -11.3% to 7.6%). CONCLUSIONS: Both airway devices had similar insertion success and clinical performance in the simulated difficult airway situation. The authors found less epiglottic downfolding and better fiberoptic view but longer insertion time with the i-gel. Our study shows that both devices are feasible for emergency airway management in patients with reduced neck movement and limited mouth opening.

A reduction in severe hypoglycaemia in type 1 diabetes in a randomized crossover study of continuous intraperitoneal compared with subcutaneous insulin infusion

Continuous intraperitoneal insulin infusion (CIPII) with the DiaPort system using regular insulin was compared to continuous subcutaneous insulin infusion (CSII) using insulin Lispro, to investigate the frequency of hypoglycemia, blood glucose control, quality of life, and safety.

Dilution and redistribution effects of rapid 2-litre infusions of 0.9% (w/v) saline and 5% (w/v) dextrose on haematological parameters and serum biochemistry in normal subjects: a double-blind crossover study

Although hypoalbuminaemia after injury may result from increased vascular permeability, dilution secondary to crystalloid infusions may contribute significantly. In this double-blind crossover study, the effects of bolus infusions of crystalloids on serum albumin, haematocrit, serum and urinary biochemistry and bioelectrical impedance analysis were measured in healthy subjects. Ten male volunteers received 2-litre infusions of 0.9% (w/v) saline or 5% (w/v) dextrose over 1 h; infusions were carried out on separate occasions, in random order. Weight, haemoglobin, serum albumin, serum and urinary biochemistry and bioelectrical impedance were measured pre-infusion and hourly for 6 h. The serum albumin concentration fell in all subjects (20% after saline; 16% after dextrose) by more than could be explained by dilution alone. This fall lasted more than 6 h after saline infusion, but values had returned to baseline 1 h after the end of the dextrose infusion. Changes in haematocrit and haemoglobin were less pronounced (7.5% after saline; 6.5% after dextrose). Whereas all the water from dextrose was excreted by 2 h after completion of the infusion, only one-third of the sodium and water from the saline had been excreted by 6 h, explaining its persistent diluting effect. Impedances rose after dextrose and fell after saline (P<0.001). Subjects voided more urine (means 1663 and 563 ml respectively) of lower osmolality (means 129 and 630 mOsm/kg respectively) and sodium content (means 26 and 95 mmol respectively) after dextrose than after saline (P<0.001). While an excess water load is excreted rapidly, an excess sodium load is excreted very slowly, even in normal subjects, and causes persistent dilution of haematocrit and serum albumin. The greater than expected change in serum albumin concentration when compared with that of haemoglobin suggests that, while dilution is responsible for the latter, redistribution also has a role in the former. Changes in bioelectrical impedance may reflect the electrolyte content rather than the volume of the infusate, and may be unreliable for clinical purposes.

Improvement of cardiac function with device-based diaphragmatic stimulation in chronic heart failure patients: the randomized, open-label, crossover Epiphrenic II Pilot Trial.

AIMS Device-based pacing-induced diaphragmatic stimulation (PIDS) may have therapeutic potential for chronic heart failure (HF) patients. We studied the effects of PIDS on cardiac function and functional outcomes. METHODS AND RESULTS In 24 chronic HF patients with CRT, an additional electrode was attached to the left diaphragm. Randomized into two groups, patients received the following PIDS modes for 3 weeks in a different sequence: (i) PIDS off (control group); (ii) PIDS 0 ms mode (PIDS simultaneously with ventricular CRT pulse); or (iii) PIDS optimized mode (PIDS with optimized delay to ventricular CRT pulse). For PIDS optimization, acoustic cardiography was used. Effects of each PIDS mode on dyspnoea, power during exercise testing, and LVEF were assessed. Dyspnoea improved with the PIDS 0 ms mode (P = 0.057) and the PIDS optimized mode (P = 0.034) as compared with the control group. Maximal power increased from median 100.5 W in the control group to 104.0 W in the PIDS 0 ms mode (P = 0.092) and 109.5 W in the PIDS optimized mode (P = 0.022). Median LVEF was 33.5% in the control group, 33.0% in the PIDS 0 ms mode, and 37.0% in the PIDS optimized mode (P = 0.763 and P = 0.009 as compared with the control group, respectively). PIDS was asymptomatic in all patients. CONCLUSION PIDS improves dyspnoea, working capacity, and LVEF in chronic HF patients over a 3 week period in addition to CRT. This pilot study demonstrates proof of principle of an innovative technology which should be confirmed in a larger sample. TRIAL REGISTRATION NCT00769678.

Entre rêves de grandeur et pragmatisme : les jeunes en milieu urbain au Burkina Faso

En dépit de sa croissance économique, le Burkina Faso reste l’un des pays les plus pauvres du monde. Dans les villes, entre 20 et 30% des moins de 30 ans sont sans travail véritablement rémunéré. Beaucoup d’entre eux vivent en situation de contrat entre les générations à l’envers, logés et nourris par leurs parents. Ce climat de précarité constante et d’incertitude quotidienne conduit à des formes spécifiques de fantaisies et d’actions. Les entretiens avec de jeunes hommes et femmes de Bobo-Dioulasso que nous avons menés à plusieurs reprises sur trois ans (étude longitudinale) mettent en lumière les conditions qui facilitent l’action en situation d’incertitude quotidienne.

Standard Model thermodynamics across the electroweak crossover

Even though the Standard Model with a Higgs mass mH = 125GeV possesses no bulk phase transition, its thermodynamics still experiences a "soft point" at temperatures around T = 160GeV, with a deviation from ideal gas thermodynamics. Such a deviation may have an effect on precision computations of weakly interacting dark matter relic abundances if their mass is in the few TeV range, or on leptogenesis scenarios operating in this temperature range. By making use of results from lattice simulations based on a dimensionally reduced effective field theory, we estimate the relevant thermodynamic functions across the crossover. The results are tabulated in a numerical form permitting for their insertion as a background equation of state into cosmological particle production/decoupling codes. We find that Higgs dynamics induces a non-trivial "structure" visible e.g. in the heat capacity, but that in general the largest radiative corrections originate from QCD effects, reducing the energy density by a couple of percent from the free value even at T > 160GeV.