[Patient dissatisfaction with postoperative pain: what are the main reasons?]. / Incidences et causes d'insatisfaction des patients vis-à-vis de la prise en charge de la douleur postopératoire.

INTRODUCTION: Patient satisfaction regarding postoperative pain management (POPM) is not always correlated with pain level relief. OBJECTIVE: To evaluate the percentage of satisfied patients while splitting satisfaction related with nurses, anaesthesiologists and surgeons during 48h postoperative period. PATIENTS AND METHODS: The study was performed in 2007 by two investigators in six different surgical suites in a university hospital. Approximatively 15 patients have been randomly selected in each surgical ward. Each patient received during the first or second postoperative day an anonymous questionnaire and was required to complete it with the investigator assistance if necessary. Questions requiring a yes-or-no reply assessed the patient's satisfaction with POPM performed by nurses, surgeons, and anaesthesiologists. In case of dissatisfaction, patients were invited to explain the reasons. RESULTS: Ninety-two patients were included, 5% of the patients were not satisfied with nurse POPM and nearly 15% were not satisfied with anaesthesiologist or surgeon POPM. The main reasons of dissatisfaction with nurses were the excessive delays between requesting and receiving an analgesic and because of the significant discrepancies in POPM between nurses. Patient discontent regarding surgeons was explained by the lack of interest of the latter for POPM. Patient discontent regarding anaesthesiologists was explained by the lack of anaesthesiologist visit in the postoperative period. CONCLUSION: There is a relationship between patient dissatisfaction and the lack of attention for POPM by surgeons and the lack of postoperative visit by the anaesthesiologist. A postoperative visit by a team of anaesthesia nurses should improve patient satisfaction with POPM.

[Occupational exposure and chronic heart failure severity]. / Esposizione professionale e gravità dello scompenso cardiaco cronico.

Chronic heart failure (CHF) is characterized by the inability of the heart to supply the body with sufficient amount of blood for metabolic and circulatory needs. The main risk factors for CHF development are: hypertension, type 2 diabetes, obesity, smoking, chronic kidney diseases. Many occupational exposures, such as extremes of heat or cold temperatures, prolonged exposure to noise, vibrations, pesticides, can contribute to etiology of this disease. The aim of our study was to evaluate if work can affect CHF severity. We analyzed retrospectively the first 76 smokers aged over 65 years who presented to the outpatient Clinic of Chronic Heart Failure. The patients were divided in 4 groups based on their previous job: white-collars, farmers, steelworkers and subjects performing different occupational activities (hairdressers, firemen, masons). Our results showed that farmers had a reduced left ventricular ejection fraction compared with white-collars (p = 0.0045) although NYHA class and the presence/absence of CHF risk factors were not different between the two groups. This data suggests that the farmer job could be associated with the severity of CHF.

Reproductive toxicity of exemestane, an antitumoral aromatase inactivator, in rats and rabbits.

Exemestane is an orally active, irreversible inactivator of aromatase, structurally related to the natural substrate androstenedione, in clinical use at 25 mg daily for the treatment of advanced breast cancer in postmenopausal women. The reproductive and developmental toxicity of exemestane was assessed in rats and rabbits with oral administration. Pivotal experiments included a fertility study (Segment I), in which female rats received exemestane doses of 4, 20, or 100 mg/kg/day from two weeks premating until GD 20 (cesarean-sectioned dams), or until GD 15 and then from D 1 to D 21 postpartum (dams allowed to deliver), and developmental toxicity studies (Segment II), in which rats and rabbits were treated from GD 6 through GD 17 (rats) or GD 18 (rabbits) at doses of 10, 50, 250, or 810 mg/kg/day and 30, 90, or 270 mg/kg/day, respectively. All rabbits and two-thirds of the rats were cesarean sectioned toward the end of pregnancy to determine litter parameters and examine structural abnormalities in the fetuses; the remaining one-third of the rats was allowed to litter and rear pups to weaning. No pivotal male fertility or peri- and postnatal studies were performed, taking into consideration the therapeutic use. Postnatal effects on the first generation offspring were assessed in both studies in rats, in the portion of dams allowed to deliver. Their F1 offspring were raised to adulthood, when they were evaluated for reproductive performance, and the F1 females were terminated on GD 20. The dosing schedule for the Segment I study in rats, which included a postnatal component, was established to exclude exposure before and during parturition (by withdrawing treatment from GD 16 until the end of parturition). This withdrawal of treatment was put in place because in a preliminary study with treatment including the peripartum period, doses from 5 to 200 mg/kg/day prolonged gestation and interfered with parturition.Overall, studies in rats showed that female fertility was not affected up to 100 mg/kg/day, but doses higher than 4 mg/kg/day, which is approximately the pharmacologically active dose (ED50 = 3.7 mg/kg), prolonged gestation and impaired parturition, leading to maternal deaths in labor and perinatal deaths of offspring. Rats killed on GD 20 showed nondose-related increases in resorptions at doses higher than 10 mg/kg/day, a reduction in fetal body weights at 20 and 100 mg/kg/day (fertility study) and 810 mg/kg/day (developmental toxicity study), and an increase in placental weights at all doses. Female fetuses exposed in utero until GD 20 at 100 mg/kg/day showed an increase in the anogenital distance, very likely related to an increase of the potent androgen DHT as a consequence of aromatase inhibition. Morphologic examinations in fetuses and born pups that were exposed in utero up to the end of the organogenesis period, as well as postnatal investigations on offspring up to adulthood, showed no treatment-related effects. In a developmental toxicity study in rabbits, treatment at 270 mg/kg/day affected maternal food intake and body weight gain, caused abortion or total resorption in about 30% of pregnant females, and reduced body weight and numbers of live fetuses, but did not affect fetal morphology. It was concluded that exemestane did not affect parturition in rats at 4 mg/kg/day or pregnancy in rabbits at 90 mg/kg/day (about 1.5 and 70 times the human dose, respectively, on a mg/m2 basis) and was not teratogenic in rats and rabbits. Exemestane is marketed for use only in postmenopausal women. Its labeling includes a contraindication to use in pregnant or lactating women.

Terminology of developmental abnormalities in common laboratory mammals (version 1).

This paper presents the first version of an internationally-developed glossary of terms for structural developmental abnormalities in common laboratory animals. The glossary is put forward by the International Federation of Teratology Societies (IFTS) Committee on International Harmonization of Nomenclature in Developmental Toxicology, and represents considerable progress toward harmonization of terminology in this area. The purpose of this effort is to provide a common vocabulary that will reduce confusion and ambiguity in the description of developmental effects, particularly in submissions to regulatory agencies worldwide. The glossary contains a primary term or phrase, a definition of the abnormality, and notes, where appropriate. Selected synonyms or related terms, which reflect a similar or closely related concept, are noted. Nonpreferred terms are indicated where their usage may be incorrect. Modifying terms used repeatedly in the glossary (e.g., absent, branched) are listed and defined separately, instead of repeating their definitions for each observation. Syndrome names are generally excluded from the glossary, but are listed separately in an appendix. The glossary is organized into broad sections for external, visceral, and skeletal observations, then subdivided into regions, structures, or organs in a general overall head to tail sequence. Numbering is sequential, and not in any regional or hierarchical order. Uses and misuses of the glossary are discussed. Comments, questions, suggestions, and additions from practitioners in the field of developmental toxicology are welcomed on the organization of the glossary as well as on the specific terms and definitions. Updates of the glossary are planned based on the comments received.

Reproductive toxicity of cabergoline in mice, rats, and rabbits.

Cabergoline, a new dopaminergic ergot derivative with potent long-lasting prolactin (PRL)-lowering properties, was assessed using standard reproductive studies in the mouse, rat, and rabbit with oral administration. Because of the compound's pharmacologic activity, several aspects remain incompletely explored in the rat, in which prolactin is the luteotrophic hormone. A fertility study in female rats was possible only at very low doses (0.5, 1, and 2 micrograms/kg/d) because higher doses completely inhibited implantation. In male rats no adverse effects were seen on male reproductive performance or on the offspring at doses up to 320 micrograms/kg/d given for 10 weeks prior to mating with untreated females. In a developmental toxicity study in rats treated from day 6 to day 15 of gestation at doses (6.25, 12.5, and 25 micrograms/kg/d) not exceeding the active dose for inhibition of egg nidation (ED50 = 25 micrograms/kg), a high incidence of total litter loss occurred as a reflection of inhibition of egg nidation at the highest dose, but embryofetal development was not impaired in litters reaching term. An exploratory study at 30 or 1000 micrograms/kg/d with treatment from day 5 of gestation or later demonstrated that cabergoline did not affect the maintenance of pregnancy at 30 micrograms/kg/d given from day 7 or later, or at 1000 micrograms/kg/d given from day 9. Doses of 500, 2000, and 8000 micrograms/kg/d (treatment from day 6 to day 15 of gestation) did not inhibit egg nidation in mice and showed no adverse effects on intrauterine development. Doses ranging from 5 to 8000 micrograms/kg/d administered from day 6 to day 18 of gestation in the rabbit were associated with maternal effects, including a reduction in body weight gain and food and water intake starting from 500 micrograms/kg/d and increased reactivity at the highest doses (4000 and 8000 micrograms/kg/d). Effects on intrauterine development were restricted to a reduction in mean fetal and placental weights at 4000 and 8000 micrograms/kg/d. In peri- and postnatal studies in rats (treatment from day 15 or 17 of gestation to weaning) cabergoline did not affect fetal development and parturition up to 100 micrograms/kg/d, but strongly inhibited milk secretion starting from 10 micrograms/kg/d, thus leaving unexplored the postnatal phase at higher doses. When neonatal rats (born from untreated dams) were treated directly with cabergoline at 10, 30, and 90 micrograms/kg/d from day 7 to 13 after birth, treatment was well tolerated up to the highest dose tested (90 micrograms/kg/d). It was concluded that cabergoline did not impair fertility in the male rat, was not teratogenic in mice and rabbits, did not affect the latter phase of gestation or parturition in the rat, and was not toxic when administered directly to neonatal rats.

Reproductive toxicology guidelines: comparison and application.

Reproductive toxicity studies currently recommended by the three principal regulatory agencies, the United States Food and Drug Administration (FDA), the Committee for Proprietary Medicinal Products (CPMP) of the European Economic Community and the Japanese Ministry of Health and Welfare (MHW), have a three-segment design, with essentially similar objectives in identifying any possible adverse effects of medicinal products on all stages of the reproductive process in animals, in order to evaluate the potential risk in man. However, differences exist between the various guidelines which give rise to considerable difficulties in amalgamating experimental designs to comply with all three agencies. The main differences are between Western and Japanese recommendations and can be identified in two points which are cause for debate and form an obstacle to the mutual acceptance of studies: a) the treatment periods during pregnancy and b) the extent of studies on the progeny reared to maturity. Both points concern solely studies in rodents and are based on a different approach to the subject. Advantages and disadvantages of the differences in each study segment are considered in relation to practical applications. In comparing recommendations from different agencies, shortcomings in the instructions and nebulous or questionable requirements, but also valuable directives, are highlighted, in the hope that regulatory authorities can be encouraged to provide exhaustive information and instructions and more explicit policies in the new coordinated guidelines which are expected as a result of international harmonization. To this end, the need for greater flexibility is stressed, since the conventional designs of the segments often prove inapplicable or are deemed inadequate or unnecessary in the case of drugs whose pharmacological activity interferes with the reproductive process or which are intended for particular therapeutic modalities or purposes. In particular, regulatory authorities are urged to provide specific, coordinated guidelines for antitumor agents, taking into account that their technical application in animals should reflect treatment modalities and therapeutic uses in humans.

Effect of maternal diet on ganglioside distribution in fetal rat brain.

Female rats were fed a diet with low protein content or with low and high amount of essential fatty acids (EFA). Ganglioside content and distribution were analyzed in the brain of animals at two different periods of fetal life (15th or 20th day). In the fetuses from mothers fed the diet with low amount of EFA the content of ganglioside is significantly lower than in the control group. The three diets resulted in the modification of ganglioside pattern, mainly for the animals on the 15th day of gestation.