Non-medical caregivers and the use of intraperitoneal chemotherapy in the operating theatre: A survey on the perception of safety.

BACKGROUND: In the last two decades, intraperitoneal(IP) chemotherapy during surgery achieved recognition in the management of peritoneal metastases. Occupational hazard became a concern leading to standardized safety measures. The aim of this study is to evaluate the perceived level of information and protection among the non-medical caregivers involved in HIPEC and PIPAC in a high-volume center. METHODS: All non-medical caregivers in the operating theatre of our institution were asked to answer a questionnaire between April and May 2018. The questionnaire included multiple choice questions and open questions structured in four parts: demographic variables, perceived level of information, perceived level of protection, interest in further education. RESULTS: Forty-nine caregivers agreed to answer the questionnaire. All identified IP chemotherapy as an occupational risk. Thirty-eight persons (77.55%) trusted the protective value of safety measures during HIPEC compared to 32 (65.3%) during PIPAC. A total of 29 persons (59.18%) used some of the measures while 16 (32.65%) used all of them. Main reasons of non-use were slips and lapses (7 persons) and lack of comfort (4 persons). A total of 34 caregivers considered the level of information about safety protocols as good or very good (69%). A total of 46 persons considered the level of protection as satisfying or excellent (93.87%). A total of 36 (73.47%) interviewees expressed the need of receiving more information. CONCLUSIONS: The present study shows that non-medical caregivers in the operating theatres are aware of the occupational hazards related to the use of IP chemotherapy. The use of protective measures is associated with decreased level of perceived risk. However there is a high need of continuous education on this subject for the involved personnel.

Changes in qualitative and quantitative ultrasound assessment of the gastric antrum before and after elective caesarean section in term pregnant women: a prospective cohort study.

Ultrasound measurement of the antral cross-sectional area allows a quantitative estimate of gastric contents in non-pregnant adults, but this relationship may be affected by compression of the stomach exerted by the gravid uterus during pregnancy. This study aimed to assess differences in quantitative (Perlas score) and qualitative (antral cross-sectional area) ultrasound assessments of the gastric antrum performed immediately before and after caesarean section. Forty-three women having elective caesarean section performed under spinal anaesthesia were studied in the semirecumbent and semirecumbent-right lateral positions. Thirty-nine women showed no change in stomach contents using the Perlas score between the two measurement periods; four women showed a change, but by one grade only. The median (IQR [range]) antral cross-sectional area was 323 (243-495 [103-908]) mm2 before, and 237 (165-377 [112-762]) mm2 after, caesarean section in the semirecumbent position (p = 0.001); the comparable values in the semirecumbent-right lateral position were 418 (310-640 [161-1238]) mm2 and 362 (280-491 [137-1231]) mm2 (p = 0.09). The distance between the skin and the antrum, and the aorta and the antrum, decreased significantly in both positions after surgery. We suggest that our results indicate that stomach contents remain largely unchanged in women having elective caesarean section, but antral cross-sectional area decreases, especially in the semirecumbent position, related to a change in the position of the stomach within the abdomen. This implies that the relationship of antral cross-sectional area to volume of stomach contents, which has been determined for non-pregnant subjects, may not apply in term pregnant women.

Prostaglandin E2 excitatory effects on rat urinary bladder: a comparison between the ß-adrenoceptor modulation of non-voiding activity in vivo and micro-contractile activity in vitro.

Prostaglandin E2 (PGE2) is well known to modulate urinary bladder functions, but it is also thought to be involved in the pathophysiology of lower urinary tract dysfunctions, since high levels of PGE2 have been found in overactive bladder (OAB) patients. ß-Adrenoceptors are major players in detrusor muscle relaxation, and the selective ß3-adrenoceptor (AR) agonist mirabegron was recently approved for the treatment of overactive bladder (OAB). ß-Adrenoceptor modulation of PGE2 excitatory effects on bladder detrusor muscle was investigated by i.v. mirabegron after intravesical PGE2 infusion in conscious rats. Non-voiding activity (NVA) was assessed under isovolumetric conditions. In addition, mirabegron and isoprenaline (0.01-10 µM) were studied on PGE2-increased micro-contractile activity during isometric tension recordings of intact isolated bladder muscle strips. Our investigations showed that PGE2 dramatically increased NVA in vivo and spontaneous micro-contractions in vitro. In vivo administration of mirabegron (0.1, 0.3 and 3 mg/kg) reduced PGE2-augmented NVA in dose-dependent manner, while the PGE2-increased micro-contractions in isolated bladder strips were poorly inhibited. Isoprenaline inhibited PGE2-augmented micro-contractions in a concentration-dependent manner and had a higher potency compared to mirabegron. The apparent pKB of 7.25 for metoprolol at the isoprenaline concentration-response curve for PGE2-augmented micro-contractions suggests a ß1-AR-mediated.

Beta adrenergic modulation of spontaneous microcontractions and electrical field-stimulated contractions in isolated strips of rat urinary bladder from normal animals and animals with partial bladder outflow obstruction.

Spontaneous microcontractions and electrical field stimulation (EFS)-evoked contractions in isolated rat bladder strips from normal and from 6 weeks partial bladder outflow obstruction (pBOO) animals were studied to identify the potential site of action for the ß3-adrenoceptor (AR) agonist mirabegron in detrusor overactivity in rats. For this, effects of the ß-AR agonist isoprenaline and mirabegron were tested in presence or absence of selective antagonists for ß-AR subtypes, namely CGP-20712A for ß1-AR, ICI-118,551 for ß2-AR, and L-748,337 for ß3-AR. In detrusor strips from both normal and obstructed animals, EFS-induced contractions were weakly affected by isoprenaline and even less so by mirabegron. In contrast, microcontraction activity was more potently reduced by isoprenaline (pIC50 7.3; Emax ±85 %), whereas mirabegron showed a small effect. In pBOO strips, concentration response curves for isoprenaline and mirabegron at inhibition of EFS and spontaneous microcontractions were similar to those in normal strips. Isoprenaline-induced inhibition of microcontractions and EFS was antagonized by the ß1-AR antagonist, but not by the ß2- and ß3-AR antagonists. In the context of ß3-AR-mediated bladder functions for mirabegron in other experiments, the current data question a role for effects at spontaneous microcontractions, or neurogenic detrusor stimulation in the mode of action for mirabegron in vivo, since functional bladder effects for mirabegron are reported to occur at much lower concentrations.

The characteristics of intrinsic complex micro-contractile activity in isolated strips of the rat bladder.

In the resting and un-stimulated state, the bladder wall is not quiescent and discrete contractile events, microcontractions, can be recorded in almost all species. This activity contributes to the active element of compliance and to the basal resting tension. This intrinsic activity underpins the more complex phasic activity, non-voiding activity (NVA) that can be seen to increase progressively as the bladder is filled. The NVA represents the motor component of a motor sensory system that relays information to the CNS on bladder volume. Despite the importance of this intrinsic motor activity, little is known about the mechanisms involved in its generation and modulation. The present experiments were done on isolated hemi-bladders from normal rats and measurements made of the intrinsic motor activity. Detailed analysis of the resting state reveals the presence of discrete phasic contractile events, micro-contractions that range in amplitude from 0.1-0.6 mN. These events seem to occur randomly and the basal activity has the appearance of 'noise'. An analysis of the frequency amplitude distribution of the contractile events, reveals that the total activity appears to be the sum of a number of discrete contractile units, each generating a phasic contraction about a specific mean value and with characteristic frequency. In a hemi-bladder, there are between 20-30 units generating the activity at rest. Using the timed integral of the activity (product of amplitude and frequency), it was noted that the activity was increased by the muscarinic agonist carbachol, but it was decreased by the ß-adrenergic agonist isoprenaline. Stretching the preparations also increased the activity. Using these observations, a simple model of the structural and functional organisation of the isolated rat bladder is proposed: the wall appears to be arranged into a number of discrete motor units acting independently. However, the activity can be stimulated or inhibited by pharmacological agents and mechanically (stretch). The possible relevance of this activity, its relationship to NVA and in relation to the mode of action of drugs are discussed. [Corrected]

Effects of ρ-Da1a a peptidic α(1) (A) -adrenoceptor antagonist in human isolated prostatic adenoma and anaesthetized rats.

BACKGROUND AND PURPOSE: ρ-Da1a, a 65 amino-acid peptide, has subnanomolar affinity and high selectivity for the human α(1) (A) -adrenoceptor subtype. The purpose of this study was to characterize the pharmacological effects of ρ-Da1a on prostatic function, both in vivo and in vitro. EXPERIMENTAL APPROACH: ρ-Da1a was tested as an antagonist of adrenaline-induced effects on COS cells transfected with the human α(1) (A) -adrenoceptor as well as on human isolated prostatic adenoma obtained from patients suffering from benign prostatic hyperplasia. Moreover, we compared the effects of ρ-Da1a and tamsulosin on phenylephrine (PHE)-induced increases in intra-urethral (IUP) and arterial pressures (AP) in anaesthetized rats, following i.v. or p.o. administration. KEY RESULTS: On COS cells expressing human α(1) (A) -adrenoceptors and on human prostatic strips, ρ-Da1a inhibited adrenaline- and noradrenaline-induced effects. In anaesthetized rats, ρ-Da1a and tamsulosin administered i.v. 30 min before PHE significantly antagonized the effects of PHE on IUP. The pK(B) values for tamsulosin and ρ-Da1a for this effect were similar. With regards to AP, ρ-Da1a only reduced the effect of PHE on AP at the lowest dose tested (10 µg·kg(-1) ), whereas tamsulosin significantly reduced PHE effects at doses between 10 and 150 µg·kg(-1) . CONCLUSIONS AND IMPLICATIONS: ρ-Da1a exhibited a relevant effect on IUP and a small effect on AP. In contrast, tamsulosin antagonized the effects of PHE on both IUP and AP. We conclude that ρ-Da1a is more uroselective than tamsulosin. ρ-Da1a is the most selective peptidic antagonist for α(1A) -adenoceptors identified to date and could be a new treatment for various urological diseases.

Stimulation of the ADRB3 adrenergic receptor induces relaxation of human placental arteries: influence of preeclampsia.

Preeclampsia, which complicates 3-8% of pregnancies, is one of the leading causes of neonatal morbidity and mortality. Its pathophysiology remains unclear. The aim of the present study was to investigate the presence and the role of beta2- and beta2-adrenergic receptors (ADRB2 and ADRB3, respectively) in human placental arteries and to assess the influence of preeclampsia on ADRB responsiveness. SR 59119A, salbutamol, and isoproterenol (ADRB3, ADRB2, and nonselective ADRB agonists, respectively) induced a concentration-dependent relaxation of placental artery rings obtained from women with uncomplicated or preeclamptic pregnancies. SR 59119A-induced relaxation was unaffected by the blockade of ADRB1 and ADRB2 by 0.1 microM propranolol but was significantly decreased by the blockade of ADRB1, ADRB2, and ADRB3 by 10 microM propranolol. Both SR 59119A and salbutamol were associated with a significant increase in cAMP production that was significantly inhibited by pretreatment with 0.1 microM propranolol only for salbutamol. SR 59119A-induced relaxation (E(max) = 28% +/- 5% vs. 45% +/- 4%, respectively) and cAMP production (2.7 +/- 0.5 vs. 4.9 +/- 0.4 pmol/mg of protein, respectively; P < 0.01) were decreased in arteries obtained from preeclamptic compared to normotensive women. Both ADRB2 and ADRB3 transcripts were expressed at the same level between arteries from normotensive and preeclamptic women. Western blot analysis, however, revealed a decreased expression of the ADRB3 immunoreactive protein in arteries from preeclamptic compared to normotensive women. We suggest the presence of functional ADRB2 and ADRB3 in human placental arteries. Even if preeclampsia is associated with an impairment of the ADRB3 responsiveness, ADRB3 agonists may have future pharmaceutical implications in the management of pregnancy-related disorders.

Beta3-adrenoceptor is the predominant beta-adrenoceptor subtype in human myometrium and its expression is up-regulated in pregnancy.

To assess whether pregnancy might influence the functionality and expression of human myometrial beta(2)- and beta(3)-adrenoceptors (beta(2)- and beta(3)-AR), we performed functional, binding, Western blot, and molecular biology experiments in human nonpregnant and near-term pregnant myometrium. Inhibition of spontaneous contractions induced by a beta(3)-AR agonist, SR 59119A, was significantly greater in pregnant, compared with nonpregnant, myometrial strips (E'(max) = 61 +/- 5% vs. 44 +/- 5% for pregnant and nonpregnant myometrium, respectively), whereas salbutamol, a beta(2)-AR agonist, was significantly less efficient in pregnant, compared with nonpregnant, myometrium (E(max) = 29 +/- 4 vs. 54 +/- 8%). Although two populations of binding sites corresponding to beta(2)- and beta(3)-AR were identified in both nonpregnant and pregnant myometrium, we found a clear predominance of the beta(3)-AR subtype. Moreover, beta(3)-AR binding sites were up-regulated 2-fold in myometrium at the end of pregnancy. Both beta(2)- and beta(3)-AR mRNA were expressed in human nonpregnant and pregnant myometrium. Contrary to beta(2)-AR, the expression of the beta(3)-AR transcripts and immunoreactive proteins was increased in pregnant, compared with nonpregnant, myometrium. Such compelling data suggest a predominant role for beta(3)-AR in the regulation of human myometrium contractility, especially at the end of pregnancy, which might have important consequences for the clinical management of preterm labor.

The human near-term myometrial beta 3-adrenoceptor but not the beta 2-adrenoceptor is resistant to desensitisation after sustained agonist stimulation.

1. In order to compare the beta(2)- and beta(3)-adrenoceptor (beta-AR) desensitisation process in human near-term myometrium, we examined the influence of a pretreatment of myometrial strips with either a beta(2)- or a beta(3)-AR agonist (salbutamol or SR 59119A, respectively, both at 10 microm, for 5 and 15 h) on the relaxation and the cyclic adenosine monophosphate (cAMP) production induced by these agonists. 2. To assess some of the mechanisms potentially implicated in the beta-AR desensitisation process, we studied the influence of such treatment on the number of beta(2)- and beta(3)-AR binding sites, the beta(2)- and beta(3)-AR transcripts expression and the phosphodiesterase 4 (PDE4) activity. 3. Salbutamol, but not SR 59119A, concentration-response curve (CRC) was shifted by a 15 h salbutamol preincubation, with a significant difference in -log EC(20) values (6.31+/-0.13 vs 5.58+/-0.24, for control and 15 h salbutamol pretreatment, respectively, P<0.05). Neither salbutamol nor SR 59119A CRCs were modified after a 15 h preincubation with SR 59119A. 4. A 15 h exposure of myometrial strips to salbutamol significantly reduced the salbutamol-induced (0.60+/-0.26 vs 1.54+/-0.24 pmol mg(-1) protein, P<0.05), but not the SR 59119A-induced, cAMP production. No decrease in cAMP production was observed after a 15 h SR 59119A exposure. 5. A 15 h salbutamol exposure of myometrial strips significantly reduced the beta(2)- but not the beta(3)-AR binding site density, whereas no decrease in the number of beta(2)- and beta(3)-AR binding sites was observed after a 15 h SR 59119A treatment. 6. Neither PDE4 activity nor the beta(2)- and beta(3)-AR mRNA expression levels were affected by salbutamol or SR 59119A treatments. 7. Our results indicate that beta(3)-AR, but not beta(2)-AR, are resistant to the agonist-induced desensitisation. In our model, beta(2)-AR desensitisation is mediated by a decreased number of beta(2)-AR that was not explained by transcriptional regulation of the receptor.

Hypoxic vasoconstriction of rat main pulmonary artery: role of endogenous nitric oxide, potassium channels, and phosphodiesterase inhibition.

This study investigated the influence of NO, potassium (K+) channel blockade, and the phosphodiesterase inhibitors (PDEIs) theophylline (non-selective PDEI), siguazodan (PDE3I), rolipram (PDE4I), and zaprinast (PDE5I) on rat isolated main pulmonary artery hypoxic (95% N2 and 5% CO2) vasoconstriction. Hypoxic vasoconstriction increased by 27% (p < 0.01) in the presence of the NO synthase inhibitor L-NAME (10(-4) M), and by 15% (p < 0.05) in the presence of the K(ATP) channel blocker glibenclamide (10(-6) M), without potentiation by the combination of these two drugs. Hypoxic vasoconstriction decreased by 28% (p < 0.01) in presence of the Kv,-voltage-dependent channel blocker 4-aminopyridine (10(-3) M), whereas the other K+ channel blockers, charybdotoxin (BKCa, large-conductance Ca2+-sensitive K+ channels) and apamin (SKCa, small-conductance Ca2+-sensitive K+ channels) had no effect. The nonselective PDEI theophylline induced a concentration-dependent relaxation (pD2 = 4.05, Emax = 90% [expressed as a percentage of maximal relaxation induced by papaverine 10(-4) M]). Among the selective PDEIs, siguazodan was significantly (p < 0.01) more efficient than rolipram and zaprinast (Emax values were 84%, 67%, and 58%, respectively) and significantly (p < 0.05) more potent than zaprinast (pD2 values were 6.48, 6.34, and 6.16 for siguazodan, rolipram, and zaprinast). Glibenclamide and L-NAME significantly (p < 0.05) shifted the concentration-response curve (CRC) for zaprinast to the right, and L-NAME shifted the CRC significantly to the right for siguazodan. In the presence of L-NAME, glibenclamide had no effect on the CRC of zaprinast. We conclude that (a) NO exerts a permanent inhibitory effect against hypoxic vasoconstriction that might be mediated in part by an activation of K(ATP) channels; (b) a 4-aminopyridine-sensitive K+ channel is involved in vasoconstriction under hypoxic conditions; (c) PDEs 3 and 5 are the predominant PDE isoforms in rat pulmonary artery relaxation; and (d) NO and K(ATP), but neither BK(Ca), SK(Ca), nor Kv channels, are involved in the relaxant effect of PDEIs.

Risks and routes for ventilator-associated pneumonia with Pseudomonas aeruginosa.

In a prospective study, we screened specimens from 190 mechanically ventilated patients hospitalized in a surgical intensive care unit, and from the environment to assess risks and routes of colonization/infection. Specimens from various sites were collected on admission and once a week throughout each patient's stay. All P. aeruginosa isolates were typed by determination of DNA patterns. Data were collected from patients to identify risk factors. In vitro production of exoenzymes of different strains were compared. Forty-four patients were colonized with P. aeruginosa on the bronchopulmonary tract and 13 suffered from pneumonia. The 7-d and 14-d Kaplan-Meier rates of colonization were 2.21 and 7.03%. Twenty-one patterns of bronchopulmonary tract isolates were isolated from single patients and 10 from several patients. The lower airway was often the first site of colonization. The contribution of environment to patient colonization appeared to be small. The length of hospitalization, the previous use of third-generation cephalosporins less effective against P. aeruginosa, and chronic obstructive pulmonary disease were the most significant predictors of colonization/infection. The in vitro exoprotein production was not correlated with the presence of pneumonia. Our study may be useful in identifying which patients in the mechanically ventilated population are at greater risk of P. aeruginosa pneumonia.

Association of private isolation rooms with ventilator-associated Acinetobacter baumanii pneumonia in a surgical intensive-care unit.

OBJECTIVE: To determine the rates and routes of Acinetobacter baumanii colonization and pneumonia among ventilated patients in a surgical intensive-care unit (SICU) before and after architectural modifications. DESIGN: A nonsequential study comparing two groups of patients. All isolates from systematic and clinical samples were genotyped by pulsed-field gel electrophoresis (PFGE). Records of patients hospitalized during the first and second periods were reviewed and findings were compared. Between the two periods, the SICU was remodeled from enclosed isolation rooms and open rooms to only enclosed isolation rooms with handwashing facilities in each room. SETTING AND PATIENTS: All patients hospitalized and mechanically ventilated for more than 48 hours in the 15-bed SICU of the University Hospital of Besançon (France). RESULTS: For the first and second periods, the rates of colonization were, respectively, 28.1% and 5.0% of patients (P < 10(-7); relative risk [RR], 2.23; 95% confidence interval [CI95], 1.8-2.75) and the specific rates of bronchopulmonary (BP) colonization were, respectively, 9.1 and 0.5 per 1,000 days of mechanical ventilation (P < 10(-5). Seven major PFGE isolate types were identified, 4 of which were isolated from 44 of the 47 colonized or infected patients. Logistic regression analysis showed that colonization was not associated with patient characteristics. CONCLUSION: Conversion from open rooms to isolation rooms may help control nosocomial BP tract acquisition of A baumanii in mechanically ventilated patients hospitalized in an SICU.

Nasal carriage of Staphylococcus aureus and cross-contamination in a surgical intensive care unit: efficacy of mupirocin ointment.

A six month prospective study was carried out in a surgical intensive care unit (SICU) of a university hospital to assess the incidence and routes of exogenous colonization by Staphylococcus aureus. A total of 157 patients were included in the study. One thousand one hundred and eleven specimens (nasal, surgical wound swabs, tracheal secretions obtained on admission and once a week thereafter, and all clinical specimens) were collected over a four month period from patients without nasal decontamination (A). They were compared with 729 specimens collected over a two month period from patients treated with nasal mupirocin ointment (B). All S. aureus strains were typed by restriction fragment length polymorphism (RFLP) pulsed-field gel electrophoresis after SmaI macrorestriction. The nasal colonization rates on admission were 25.5 and 32.7% in groups A and B, respectively. Thirty-one untreated patients (31.3%) and three patients (5.1%) treated with nasal ointment, acquired the nasal S. aureus in the SICU (P = 0.00027). Nasal carriers were more frequently colonized in the bronchopulmonary tract (Bp) and surgical wound (Sw) (62%) than patients who were not nasal carriers (14%) (P < 0.00001). The patterns were identical for nasal, Bp and Sw strains from the same patient. RFLP analysis characterized seven epidemic strains of methicillin-resistant S. aureus (MRSA) which colonized 60% of group A and 9% of group B patients (P < 0.00001). The bronchopulmonary tract infection rate was reduced in group B (P = 0.032). In conclusion, in an SICU, nasal carriage of S. aureus appeared to be the source of endogenous and cross-colonization. The use of nasal mupirocin ointment reduced the incidence of Bp and Sw colonization, as well as the MRSA infection rate.

[Surgery of the aortic bifurcation and heart diseases: peroperative hemodynamics]. / Chirurgie du carrefour aortique et cardiopathies: profil hémodynamique per-opératoire.

During aorto-biiliac by-pass, patients with heart disease are exposed at many haemodynamic problems. Mixed venous oxygen saturation monitoring help anesthetist along clamping and unclamping periods. This study concerning 13 patients with pre-operative NYHA class II and III congestive heart disease, discusses therapeutic algorithm especially for choosing inotropic or vasodilatator drugs.

[Prevalence of and changes in hepatitis C virus antibodies in 64 patients with liver transplant]. / Prévalence et évolution des anticorps dirigés contre le virus de l'hépatite C chez soixante-quatre transplantés hépatiques.

The aim of this retrospective study was to assess the prevalence of hepatitis C virus antibodies and their follow-up in a series of 64 orthotopic liver transplantation patients. Indications for transplantation were cirrhosis in 28 cases, primary biliary cirrhosis in 6 cases, liver cancer in 11 cases, fulminant hepatitis in 2 cases, and alveolar echinococcosis in 17 cases. The prevalence of serum antibodies to hepatitis C virus was assessed by an ELISA test (Ortho-Diagnostic-Systems). Sera were tested before liver transplantation and every two months after. Twenty-nine patients seronegative before transplantation remained negative. Four patients seropositive before liver transplantation remained seropositive. Twenty-eight patients seropositive before transplantation, became seronegative after, and 3 patients seronegative before transplantation became seropositive after. The prevalence of seroconversion was 9.3 percent. The prevalence of seropositive patients after transplantation was 11 percent. The high number of seropositive patients before transplantation (50 percent) could be explained by false positive results. Seropositivity before transplantation appeared to be related to hypergammaglobulinemia (p less than 0.001). This hypothesis was confirmed a posteriori by a concomitant disappearance of both seropositivity and hypergammaglobulinemia after transplantation in 62 percent of patients.