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Biomedical subjects

P Jolliet

Publications and source records attributed to P Jolliet.

At least 19 recordsLinked to original sources

High-performance liquid chromatographic assay to determine the plasma levels of HIV-protease inhibitors (amprenavir, indinavir, nelfinavir, ritonavir and saquinavir) and the non-nucleoside reverse transcriptase inhibitor (nevirapine) after liquid-liquid extraction.

A single HPLC assay was developed for therapeutic drug monitoring of 5 HIV protease inhibitors (indinavir, amprenavir, saquinavir, ritonavir, nelfinavir) and a non-nucleoside reverse transcriptase inhibitor (nevirapine) in human plasma. After liquid-liquid extraction in a mixture ethyl acetate-hexane, compounds are separated on a C18 column with a gradient elution of solvent A [acetonitrile and 0.025 M tetramethylammonium perchlorate in 0.2% aqueous trifluoroacetic acid (55:45 (v/v))] and solvent B [methanol and 0.025 M tetramethylammonium perchlorate in 0.2% aqueous trifluoroacetic acid (55:45 (v/v))]. The compounds are detected at various wavelengths: 320 nm (nevirapine), 259 nm (indinavir), 254 nm (amprenavir, nelfinavir, saquinavir) and 239 nm (ritonavir). The intra-day and inter-day precision and accuracy are lower than 15%. The limits of quantitation are 0.05 mg/l (amprenavir), 0.2 mg/l (indinavir, saquinavir, nelfinavir) and 0.4 mg/l (ritonavir, nevirapine). This method which allows to estimate simultaneously plasma levels of protease inhibitors and nevirapine can be used for therapeutic drug monitoring.

Calibration↗

Are there gender differences in the temperature profile of mice after acute antidepressant administration and exposure to two animal models of depression?

Numerous studies have reported gender differences in the rates of depression in humans, but few behavioural observations of antidepressant drug effects have been investigated in female mice. The forced swimming test (FST) is widely used as a predictor of antidepressant activity in rodents, as is the tail suspension test (TST), where immobility is objectively measured and in this last test, no hypothermia is induced by immersion in cold water. The present study investigated gender differences in the temperature profile of mice after acute antidepressant administration (imipramine and paroxetine) and exposure to two animal models of depression. Imipramine and paroxetine were active at 32 mg/kg in male mice in the FST, whereas they were active at 8, 16 and 32 mg/kg in female mice. In the TST, for both antidepressants immobility duration was reduced at a dose of 16 and 32 mg/kg in male mice and at 32 mg/kg in female mice. No significant difference was observed between male and female mice for immobility duration. Imipramine administration, but not paroxetine, decreased the temperature at the higher dose (32 mg/kg) in male and female mice in the FST. The body temperature was reduced in male and female mice for all treatment groups after FST challenge. Imipramine (16 and 32 mg/kg in male and 32 mg/kg in female mice), paroxetine (4, 16 and 32 mg/kg in male and 4 to 32 mg/kg in female mice) attenuated the reduction in temperature due to the FST. In the TST, imipramine tends to decrease the temperature in male and female mice, even though only imipramine at a dose of 32 mg/kg in female mice significantly decreases the temperature. Paroxetine had no effect on temperature. The TST enhanced the body temperature in male and female mice. In mice, there was no difference between the sexes after imipramine or paroxetine administration in the FST and TST. Both tests can be used to predict the activity of antidepressants as the decrease or enhancement of temperature is not correlated with a reduction in immobility duration.

Animals↗

Acute hepatic steatosis complicating massive insulin overdose and excessive glucose administration.

OBJECTIVE: To describe a case of acute hepatic steatosis due to excessive administration of glucose in the setting of massive insulin overdose, a complication which is rapidly and completely reversible if glucose infusion is rapidly tapered. DESIGN: Case report, clinical. SETTING: Intensive care unit, university hospital. PATIENT: A single patient admitted to the ICU. INTERVENTION: Intravenous glucose after insulin overdose. MEASUREMENTS AND MAIN RESULTS: On the 3rd day, increases in transaminase (ASAT 420 IU/l, ALAT 610 IU/l), bilirubin (147 mmol/l) and lactate (6.8 mmol/l), a decrease in arterial pH (7.32) and slightly increased liver size on ultrasound examination suggested acute hepatic steatosis. Clinical and laboratory abnormalities resolved rapidly after discontinuation of excessive glucose infusions (1,400 g/day for 3 days). CONCLUSIONS: Very large amounts of glucose after massive insulin overdose are potentially dangerous. Even though the fear of hypoglycemia-induced neurologic damage should be a constant preoccupation in this situation, glucose administration should be titrated on closely monitored blood glucose levels.

Acidosis, Lactic↗

Non-invasive pressure support ventilation in severe community-acquired pneumonia.

OBJECTIVE: To explore three aspects of non-invasive pressure support ventilation (NIPSV) applied by face mask to patients with acute respiratory failure (ARF) due to severe community-acquired pneumonia (CAP): (1) the initial acute effects on respiratory rate, gas exchange and hemodynamics, (2) the clinical course and outcome during ICU and hospital stay, (3) the nursing workload as measured by the daily PRN 87 (Project Research in Nursing) score. SETTING: Medical ICU, University Hospital. DESIGN: Prospective, observational study. PATIENTS: Patients without any prior history of chronic lung disease, consecutively admitted to the ICU to receive NIPSV for ARF due to severe CAP. MEASUREMENTS AND RESULTS: (means +/- SD): Twenty-four patients aged 49+/-17 years, admission APACHE II 13+/-5, were included. Admission PaO2/FIO2, alveolar-arterial oxygen difference (DA-aO2) and PaCO2 were 104+/-48, 447+/-120 and 40+/-10 mmHg, respectively. All patients were normotensive. During the initial NIPSV trial respiratory rate decreased from 34+/-8 to 28+/-10 breaths/min (p < 0.001) and arterial oxygenation improved (PaO2/FIO2 104+/-48 vs 153+/-49, DA-aO2 447+/-120 vs 370+/-180 mmHg, p < 0.001) while PaCO2 remained unchanged. There were no hemodynamic effects. Subsequently, a total of 133 NIPSV trials were performed (median duration 55 min, range 30-540 min) over 1-7 days. No complication occurred during NIPSV. Sixteen patients were intubated (66%) 1.3+/-1 days after inclusion. Upon inclusion, the patients who were subsequently intubated were older (55+/-15 vs 37+/-12 years) and more severely hypoxemic (63+/-11 vs 80+/-15 mmHg, p < 0.05) than those not requiring intubation. Eight patients died (33 %), all in the intubated group. Median lengths of stay in the ICU and hospital were longer in intubated patients (ICU 16 days, range 3-64 vs 6 days, range 3-7, p < 0.05; hospital 23 days, range 9-77 vs 9.5 days, range 4-42, p < 0.05). Mean daily total PRN points were stable throughout the NIPSV period and were not different between the groups. Only 14% of PRN points resulted from respiratory therapy interventions. PRN score was higher during the first 24 h following intubation than during the first 24 h of NIPSV (278+/-55 vs 228+/-24 points, p < 0.05). CONCLUSION: Despite initial improvement in arterial oxygenation with NIPSV in patients with ARF due to severe CAP, the intubation rate is high. However, the more favorable outcome and shorter ICU and hospital stays when intubation is avoided, as well as the short delay required to assess the success or failure of NIPSV warrants a trial of NIPSV in this setting. The nursing workload remains stable during NIPSV and does not result predominantly from respiratory therapy interventions.

Adolescent↗

Comparison of antidepressant activity in 4- and 40-week-old male mice in the forced swimming test: involvement of 5-HT1A and 5-HT1B receptors in old mice.

RATIONALE: A recent study suggested that selective serotonin reuptake inhibitors were inactive in 40-week-old male mice in the mouse forced swimming test, possibly because of alteration of 5-HT1 receptors. OBJECTIVES: The present study was aimed at investigating the action of various antidepressant drugs in 4- and 40-week-old male mice using the mouse forced swimming test and determining the involvement of 5-HT1A and 5-HT1B receptors mediating the effects. METHODS: Different classes of antidepressants [imipramine (tricyclic), maprotiline (noradrenline reuptake inhibitor), venlafaxine (mixed serotonin and noradrenaline reuptake inhibitors), fluvoxamine and sertraline (selective serotonin reuptake inhibitor)] were tested in the same randomised experimental session, alone and in combination with 5-HT1A and 5-HT1B receptor agonists [buspirone (partial 5-HT1A agonist), anpirtoline (5-HT1B agonist)] in the mouse forced swimming test. RESULTS: All antidepressants were found to be active in the mouse forced swimming test in 4-week-old mice and 40-week-old mice, with the exception of fluvoxamine in the 40-week-old mice. The anti-immobility effect after antidepressant administration was higher in 4-week-old male mice than in 40-week-old male mice. Venlafaxine is the most active antidepressant drug in 40-week-old mice. Prior administration of buspirone (0.06 mg/kg, i.p.) or anpirtoline (1 mg/kg, i.p.) enhanced the antidepressant-like effects in 4-week-old mice (except in the case of sertraline, 8 mg/kg). In elderly mice, only prior administration of buspirone enhanced the antidepressant-like effects of fluvoxamine. A neurochemical study showed that significantly higher serotonin and dopamine concentrations were found in 40-week-old control mice brains than 4-week-old control mice brains but that the noradrenaline concentration is higher in 4-week-old mice. CONCLUSION: Tricyclic, noradrenaline reuptake inhibitors and serotonin reuptake inhibitors are more active in 4-week-old mice than 40-week-old mice. Our results suggested that 5-HT1B receptors may be more altered than 5-HT1A receptors in 40-week-old mice.

Aging↗

A follow-up study of a population of schizophrenic patients treated with clozapine.

1. Clozapine is a dibenzodiazepine neuroleptic which presents the advantage of not having undesirable neurological side-effects. Its efficacy for the treatment of the symptoms of schizophrenia is known, but the use of clozapine is limited to treatment-resistant schizophrenic patients as it induces agranulocytosis with a higher incidence than that of other neuroleptic drugs. 2. The present study was designed in order to evaluate the benefit/risk of chronic treatment. The analysis was performed using the files of schizophrenic patients. These patients were not stabilized by a classical neuroleptic treatment and/or presented individual secondary effects. 3. Clozapine induced neutropenia and 1 case of agranulocytosis in 3 females. Analysis of leukocyte expression highlighted some premonitory symptoms in patients who presented neutropenia. The observation of 2 to 3 early successive peaks in leukocyte expression (between the third and tenth week of treatment) could be predictive of neutropenia in the 3 to 4 months of treatment. 4. The patients who presented a lower leukocyte base-line following a peak had a higher risk, of developing neutropenia. This might explain some late accidents beyond the first six months of treatment. 5. The present study confirmed the advantages of clozapine treatment and demonstrated that the risk of neutropenia may be diminished by the detection of premonitory symptoms and the early monitoring of patients at risk i.e. female patients and subjects with a lower leukocyte base-line.

Adult↗

[5-HT1B serotonin receptors and antidepressant effects of selective serotonin reuptake inhibitors ].

We used knockout mice and receptor antagonist strategies to investigate the contribution of the serotonin (5-hydroxytryptamine, 5-HT) 5-HT1B receptor subtype in mediating the effects of selective serotonin reuptake inhibitors (SSRIs). Using in vivo intracerebral microdialysis in awake mice, we show that a single systemic administration of paroxetine (1 or 5 mg/kg, i.p.) increased extracellular serotonin levels [5-HT]ext in the ventral hippocampus and frontal cortex of wild-type and mutant mice. However, in the ventral hippocampus, paroxetine at the two doses studied induced a larger increase in [5-HT]ext in knockout than in wild-type mice. In the frontal cortex, the effect of paroxetine was larger in mutants than in wild-type mice at the 1 mg/kg dose but not at 5 mg/kg. In addition, either the absence of the 5-HT1B receptor or its blockade with the mixed 5-HT1B/1D receptor antagonist, GR 127935, potentiates the effect of a single administration of paroxetine on [5-HT]ext more in the ventral hippocampus than in the frontal cortex. Furthermore, we demonstrate that SSRIs decrease immobility in the forced swimming test; this effect is absent in 5-HT1B knockout mice and blocked by GR 127935 in wild-type suggesting therefore that activation of 5-HT1B receptors mediate the antidepressant-like effects of SSRIs. Taken together these data demonstrate that 5-HT1B autoreceptors appear to limit the effects of SSRI on dialysate 5-HT levels particularly in the hippocampus while presynaptic 5-HT1B heteroreceptors are likely to be required for the antidepressant activity of SSRIs.

Animals↗

First report of mirtazapine-induced arthralgia.

OBJECTIVE: The aim of our work is to describe the first two cases of arthralgia associated with the antidepressant drug mirtazapine. METHOD: Descriptive analysis of two iatrogenic cases. The review of the literature was achieved by the traditional electronic methods. The French database of iatrogenic cases was consulted. RESULTS: A 53-year-old man presented with gonalgia after some weeks of mirtazapine treatment. The intensity of the arthralgia was correlated with the dosage and the adverse effect rapidly disappeared after the antidepressant therapy was stopped. A 38-year-old woman received mirtazapine for 3 months and complained of arthralgia and myalgia. This clinical picture was suspended as the drug was stopped and a positive reintroduction was observed. No other cause was found in these two patients. DISCUSSION: No similar case has been reported in the international literature, but several observations of arthralgia with mianserin are mentioned. As mirtazapine is the 6-aza derivative of the tetracyclic antidepressant mianserin, the similarities of their chemical structures begs the responsibility of mirtazapine for arthralgia.

Adult↗

Endothelin-1 blockade corrects mesenteric hypoperfusion in a porcine low cardiac output model.

OBJECTIVE: To study the importance of endothelin-1-induced vasoconstriction in a model of acute and maintained low cardiac output, by investigating regional changes within the mesenteric and particularly the intestinal mucosal circulation. DESIGN: Prospective, controlled animal study. SETTING: University-affiliated research laboratory. SUBJECTS: Thirteen fasted, anesthetized, mechanically ventilated landrace pigs. MEASUREMENTS AND MAIN RESULTS: Cardiac output, portal venous blood flow, renal arterial flow, jejunal mucosal microcirculation by laser Doppler flowmetry, jejunal capnotonometry (Pco2 gap), and jejunal mucosal oxygenation (tPo2) were monitored. Cardiac tamponade was established to reduce portal venous blood flow to a preset end point at two thirds of baseline. Measurements were made at baseline, after 90 mins of cardiac tamponade, and 90 mins after the administration of the combined endothelinA/endothelinB antagonist tezosentan at 1 mg.kg-1.hr-1 during tamponade in seven animals. Six animals served as time controls and received only the vehicle. Cardiac tamponade decreased portal venous blood flow, renal arterial flow, and laser Doppler flowmetry, whereas the Pco2 gap increased. The change in tPo2 failed to gain statistical significance (p =.08). Administration of tezosentan during tamponade restored portal venous blood flow and laser Doppler flowmetry to baseline values, increased tPo2 above baseline, and decreased Pco2 gap. No effect on renal arterial flow was observed. Investigated variables remained unchanged in control animals after induction of cardiac tamponade. CONCLUSIONS: Endothelin-1 blockade in acute cardiac failure improves mesenteric, but not renal, perfusion, illustrating the regional importance of endothelin-1-induced vasoconstriction. Importantly, endothelin-1 blockade restored mucosal blood flow and oxygenation, which might be particularly interesting considering the implications for maintenance of mucosal barrier integrity in low output states.

Animals↗

[Role of noninvasiveness ventilation in the weaning phase of mechanical ventilation].

During the last decade, noninvasive ventilation has proved to be a valuable alternative to endotracheal intubation in many patients with acute respiratory failure, allowing a reduction in morbidity, mortality and length of intensive care and hospital stay compared to conventional mechanical ventilation. Recent data from clinical studies suggest that these beneficial effects could also be extended to the weaning phase of mechanical ventilation, by reducing, in some patients at any rate, its duration and complication rate. The present paper focuses on some of these promising new aspects of noninvasive ventilation and attempts to define the possible indications and limits of this technique in the context of weaning.

Humans↗

Economic investigation of the use of three-compartment total parenteral nutrition bag: prospective randomized unblinded controlled study.

Optimal strategy for total parenteral nutrition (TPN) administration is essential both in terms of clinical effectiveness and economic efficiency. The aim of the present economic analysis was to provide a systematic and comprehensive cost comparison of the application of three currently available TPN systems: Separate Bottles (SB), Hospital-Compounded Bags (HCB) and Three-Compartment Bags (TCB). Sixty patients, admitted to the Geneva University Hospital and requiring TPN, were randomly assigned to one of the three systems. Three standard TPN formulas were prescribed to meet the patients' protein energy needs. TPN-related activities of medical, nursing and pharmacy staff were timed for the 24 hours of TPN administration. Manpower, nutrient solutions and medical supplies costs were calculated on the basis of mean Swiss salaries and hospital prices. TCB was the least expensive TPN system. SB and HCB systems' application costs were 120 and 150% of TCB cost, respectively. All intersystems cost comparisons were statistically significant (ANOVA p < or = 0.01). SB system required more items and manipulations, resulting in higher nurses manpower cost. Pharmacy overhead cost due to compounding was responsible for the higher cost of HCB system. Detailed manpower data presented in this study allow for an estimation of TPN application costs in other hospitals, using local salaries, specific product prices and compounding costs.

Cost-Benefit Analysis↗

Effects of helium-oxygen on intrinsic positive end-expiratory pressure in intubated and mechanically ventilated patients with severe chronic obstructive pulmonary disease.

OBJECTIVE: To test the hypothesis that replacing 70:30 nitrogen: oxygen (Air-O2) with 70:30 helium:oxygen (He-O2) can decrease dynamic hyperinflation ("intrinsic" positive end-expiratory pressure) in mechanically ventilated patients with chronic obstructive pulmonary disease (COPD), and to document the consequences of such an effect on arterial blood gases and hemodynamics. DESIGN: Prospective, interventional study. SETTING: Medical intensive care unit, university tertiary care center. PATIENTS: Twenty-three intubated, sedated, paralyzed, and mechanically ventilated patients with COPD enrolled within 36 hrs after intubation. INTERVENTIONS: Measurements were taken at the following time points, all with the same ventilator settings: a) baseline; b) after 45 mins with He-O2; c) 45 mins after return to Air-O2. The results were then compared to those obtained in a test lung model using the same ventilator settings. MAIN RESULTS (MEAN + SD): Trapped lung volume and intrinsic positive end-expiratory pressure decreased during He-O2 ventilation (215+/-125 mL vs. 99+/-15 mL and 9+/-2.5 cm H2O vs. 5+/-2.7 cm H2O, respectively; p < .05). Likewise, peak and mean airway pressures declined with He-O2 (30+/-5 cm H2O vs. 25+/-6 cm H2O and 8+/-2 cm H2O vs. 7+/-2 cm H2O, respectively; p < .05). These parameters all rose to their baseline values on return to Air-O2 (p < .05 vs. values during He-O2). These results were in accordance with those obtained in the test lung model. There was no modification of arterial blood gases, heart rate, or mean systemic arterial blood pressure. In 12/23 patients, a pulmonary artery catheter was in place, allowing hemodynamic measurements and venous admixture calculations. Switching to He-O2 and back to Air-O2 had no effect on pulmonary artery pressures, right and left ventricular filling pressures, cardiac output, pulmonary and systemic vascular resistance, or venous admixture. CONCLUSION: In mechanically ventilated COPD patients with intrinsic positive end-expiratory pressure, the use of He-O2 can markedly reduce trapped lung volume, intrinsic positive end-expiratory pressure, and peak and mean airway pressures. No effect was noted on hemodynamics or arterial blood gases. He-O2 might prove beneficial in this setting to reduce the risk of barotrauma, as well as to improve hemodynamics and gas exchange in patients with very high levels of intrinsic positive end-expiratory pressure.

Aged↗

Management of nutrition in European intensive care units: results of a questionnaire. Working Group on Metabolism and Nutrition of the European Society of Intensive Care Medicine.

OBJECTIVE: To describe the practical aspects of nutritional management in intensive care units (ICUs). DESIGN: A 49-item questionnaire was sent to the physician members of the European Society for Intensive Care Medicine. The issues addressed included: medical environment, assessment of nutritional status and current practice for enteral and parenteral nutrition. SETTING: 1608 questionnaires were sent in 35 European countries. ANALYSIS: The answers were pooled and stratified by country. RESULTS: 271 questionnaires were answered (response rate 17%). Assessment of nutritional status was generally based on clinical (99%) and biochemical (82%) parameters rather than on functional (24%), anthropometric (23%), immunological (18%) or questionnaire-based (11%) data. Two thirds of 2774 patients hospitalised in the corresponding ICUs at the time the questionnaire was answered were receiving nutritional support; 58% of those were fed by the enteral route, 23% by the parenteral route and 19% by combined enteral and parenteral. The preferred modality was enteral nutrition, instituted before the 48th h after admission, at a rate based on estimated caloric requirements. Specific and modified solutions were rarely used. Parenteral nutrition was less commonly used than enteral, although the practices differed between countries. It was mainly administered as hospital-made all-in-one solutions, at a rate based on calculated caloric requirements. CONCLUSIONS: European intensivists are concerned by the nutritional management of their patients. The use of nutritional support is common, essentially as early enteral feeding.

Critical Care↗

Enteral nutrition in intensive care patients: a practical approach.

Severe protein-calorie malnutrition is a major problem in many intensive care (ICU) patients, due to the increased catabolic state often associated with acute severe illness and the frequent presence of prior chronic wasting conditions. Nutritional support is thus an important part of these patient's management. Over the years, enteral nutrition (EN) has gained considerable popularity, due to its favorable effects on the digestive tract and its lower cost and rate of complications compared to parenteral nutrition. However, clinicians caring for ICU patients are often faced with contradictory data and difficult decision-making when having to determine the optimal timing and modalities of EN administration, estimation of patient requirements and choice of formulas. The purpose of this paper is to provide practical guidelines on these various aspects of enteral nutritional support, based on presently available evidence.

Contraindications↗