Pharmacokinetics of oral tapentadol in cats.

To evaluate pharmacokinetics of one dose of tapentadol hydrochloride orally administered to cats. Prospective experimental study. Five healthy adult mixed-breed cats. Each cat received 18.8 ± 1.0 mg/kg tapentadol orally. Venous blood samples were collected at time 0 (immediately prior to administration of tapentadol) 1, 2, 5, 10, 15, 30, 45, 60, 90 min, and 2, 4, 8, 12 to 24 h after drug administration. Plasma tapentadol concentrations and its metabolites were determined using ultra-performance liquid chromatography-tandem mass spectrometry. Geometric mean Tmax of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 2.3, 7.0, 6.0, and 4.6 h, respectively. Mean Cmax of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 637, 66, 1134, and 15,757 ng/mL, respectively, after administration. Mean half-life of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 2.4, 4.7, 2.9, and 10.8 h. The relative exposure of tapentadol and its metabolites were tapentadol 2.65%, desmethyltapentadol 0.54%, tapentadol-O-glucuronide 6.22%, and tapentadol-O-sulfate 90.6%. Tapentadol-O-sulfate was the predominant metabolite following the administration of oral tapentadol in cats. Further studies are warranted to evaluate the association of analgesia with plasma concentrations of tapentadol.

Determination of milk concentrations and pharmacokinetics of salicylic acid following acetylsalicylic acid (aspirin) administration in postpartum dairy cows.

The objectives of this descriptive study were to (1) describe the pharmacokinetics of salicylic acid (SA) in the milk and plasma of postpartum dairy cattle following oral administration of acetylsalicylic acid (ASA; aspirin), (2) to estimate a recommended milk withdrawal period for dairy cattle treated with ASA, and (3) to determine the effect of ASA administration on plasma prostaglandin E2 metabolite (PGEM) concentrations. Primiparous (n = 3) and multiparous (n = 7) postpartum Holstein dairy cows received 2 oral treatments with ASA at 200 mg/kg of body weight, 24 h apart. Concentrations of SA in plasma and milk from 0 h through 120 h after ASA administration were analyzed using ultra performance liquid chromatography triple quadrupole mass spectrometry and a milk withdrawal period was estimated using the United States Food and Drug Administration Milk Discard App in R. Two withdrawal periods were estimated: (1) a whole-herd treatment scenario with no dilution factor and (2) an individual animal treatment scenario with a bulk tank factor included in analysis. Plasma PGEM concentrations in samples from 0 h to 24 h after ASA administration were determined using a commercially available competitive ELISA. Milk SA concentrations were undetected in all cows by 48 h after the last ASA treatment. Secondary peaks were observed in plasma at 58 and 82 h after the last treatment and in milk at 87 h after the last treatment. In the absence of a tolerance for SA in milk, the estimated milk withdrawal periods were (1) 156 h for the whole-herd treatment scenario and (2) 120 h for the individual animal treatment scenario. Plasma PGEM concentrations were reduced compared with baseline for up to 12 h after ASA administration, with the greatest reduction observed at 2 h. Results from this study suggest that the current milk withhold recommendation for dairy cattle administered ASA may need revision to 120 h (5 d) and that ASA administration may mitigate postpartum inflammation through reduction in prostaglandin production for up to 12 h after treatment. Pharmacokinetic and milk withdrawal data from this study will inform future recommendations for extra-label use of aspirin in postpartum dairy cows. Further research is required to determine the basis for the secondary SA peaks and to elucidate the long-term effects of ASA administration on dairy cow health.

Pre-pregnancy body mass index and weight gain during pregnancy: relations with gestational diabetes and hypertension, and birth outcomes.

To study the relationship between pre-pregnancy body mass index (BMI) and weight gain during pregnancy with pregnancy and birth outcomes, with a focus on gestational diabetes and hypertension and their role in the association with fetal growth. We studied 1,884 mothers and offspring from the Eden mother-child cohort. Weight before pregnancy (W1) and weight after delivery (W2) were collected and we calculated BMI and net gestational weight gain (netGWG = (W2 - W1)/(weeks of gestation)). Gestational diabetes, hypertension gestational age and birth weight were collected. We used multivariate linear or logistic models to study the association between BMI, netGWG and pregnancy and birth outcomes, adjusting for center, maternal age and height, parity and average number of cigarettes smoked per day during pregnancy. High BMI was more strongly related to the risk of giving birth to a large-for-gestational-age (LGA) baby than high netGWG (odds ratio OR [95% CI] of 3.23 [1.86-5.60] and 1.61 [0.91-2.85], respectively). However, after excluding mothers with gestational diabetes or hypertension the ORs for LGA, respectively weakened (OR 2.57 [1.29-5.13]) for obese women and strengthened for high netGWG (OR 2.08 [1.14-3.80]). Low in comparison to normal netGWG had an OR of 2.18 [1.20-3.99] for pre-term birth, which became stronger after accounting for blood pressure and glucose disorders (OR 2.70 [1.37-5.34]). Higher net gestational weight gain was significantly associated with an increased risk of LGA only after accounting for blood pressure and glucose disorders. High gestational weight gain should not be neglected in regard to risk of LGA in women without apparent risk factors.

Influence of fetal and parental factors on intrauterine growth measurements: results of the EDEN mother-child cohort.

OBJECTIVE: In small-for-gestational-age neonates, parental and fetal characteristics can be used to distinguish between constitutionally small size and growth restriction, which is associated with a higher risk of morbidity and mortality. The aim of this study was to quantify relationships of parental and fetal characteristics with fetal ultrasound measurements. METHODS: The EDEN mother-child cohort included 2002 pregnant women with singleton pregnancies attending one of two university hospitals. Data from two routine ultrasound examinations for fetal biometry were recorded, at 20-25 and 30-35 weeks of gestation. Biparietal diameter (BPD), head circumference (HC), femur length (FL), abdominal circumference (AC) and estimated fetal weight (EFW) were studied as a function of prepregnancy maternal body mass index (BMI), maternal height, paternal height, fetal sex and gestational age. RESULTS: Data were obtained at the first scan from 1833 women and at the second scan from 1752 women. Parental anthropometric characteristics were significantly associated with ultrasound measurements at both scans. Maternal BMI was more strongly associated with AC and EFW, whereas both maternal and paternal height were more strongly associated with FL. An association was also found between fetal sex and all ultrasound measurements other than FL. CONCLUSION: Maternal and paternal anthropometric characteristics are significantly associated with ultrasound measurements in mid to late pregnancy. These relationships provide support for the use of these characteristics in ultrasound fetal size reference charts.

Using a heating cable within the abdomen to make hyperthermic intraperitoneal chemotherapy easier: feasibility and safety study in a pig model.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is a complex, expensive and time-consuming procedure. Despite its good results in the treatment of peritoneal carcinomatosis, these factors have precluded the wider use of this procedure around the world. We hypothesized that HIPEC could be performed by heating the liquid within the abdomen and thus avoiding the need for an external heating circuit and a pump. The aim of this study was to assess the feasibility and safety of an internal heating device for hyperthermic intraperitoneal chemotherapy in an experimental model. METHODS: Four large-white pigs underwent one-hour open intraperitoneal hyperthermia with closed abdomen using this new device. Constant stirring of the liquid around the viscera was performed in the first three animals, but not in the fourth one. At the end of the procedure, all of the viscera were carefully examined to look for thermal injury. Any lesion or doubtful area was removed and sent to pathologic examination. RESULTS: No adverse events occurred during surgery in any of the animals. A temperature of 42 degrees C was reached in an average time of 14 min and maintained homogeneously between 42 degrees C and 43 degrees C for one hour. No visceral injury was detected in the first three animals. Three foci of thermal injury to the mucosa were detected in the absence of stirring (fourth animal). CONCLUSION: Heating the solution within the abdomen during hyperthermic intraperitoneal chemotherapy is feasible, safe and achieves perfect thermal homogeneity. This device provides a time-saving inexpensive way to perform intraperitoneal hyperthermic chemotherapy.

[HELLP syndrome: the ten commandments]. / Le syndrome HELLP: les dix commandements.

The internist has a role to play in the practical approach of HELLP syndrome, a disease which can differ according to its symptoms, course and causes. Any recent epigastric pain during the end of pregnancy must be considered as a symptom of HELLP syndrome. Liver disease together with thrombocytopenia may be present even without any renovascular involvement. The disease can be threatening for the mother and lead to the foetal death. It can be sometimes difficult to be distinguished from thrombotic microangiopathy. Treatment consists mainly in rapid discontinuation of pregnancy. Steroid therapy could allow to simplify anaesthesia procedures and to avoid blood transfusion. Early-onset HELLP syndrome could be a marker a chronic nephropathy or a thrombophilic disorder. The HELLP syndrome is a very demonstrative example of the help the internist can afford to the obstetrician in the management of pregnancy-associated disorders.

[Obstructive Sleep Apnea Syndrom during pregnancy: prevalence of main symptoms and relationship with Pregnancy Induced-Hypertension and Intra-Uterine Growth Retardation]. / Le syndrome d'apnées du sommeil pendant la grossesse: prévalence des symptômes cliniques et corrélation avec la pathologie vasculaire gravidique.

OBJECTIVE: To investigate the frequency of main symptoms of Obstructive Sleep Apnea Syndrom (OSAS) and their relationship with Pregnancy Induced-Hypertension (PIH) as well as Intrauterine Growth Retardation (IGR) as suggested by recent studies. METHODOLOGY: Four hundred (and) thirty-eight enquiry forms completed during post-partum period were analysed, after exclusion of multiple pregnancies. Collected data were demographic characteristics, obstetrical events, sleep disorders during last trimester, screening of snoring and vigilance troubles with an Epworth score. RESULTS: Forty-five percentages of the patients reported to have habitual snoring during pregnancy. Among these, 85% were non-snorers before pregnancy. Daytime somnolence concerned 84,5% of the population with an Epworth score significatively increased (P<0,0001). The prevalence of PIH was found to be 4,5%, with two apparently independent risk factors: the body mass index (OR=1,1) and an association between snoring and increased vigilance trouble (OR=2,6). No statistical difference was found concerning IGR. CONCLUSIONS: SAS symptoms are frequent during pregnancy and snoring appears to be linked with PIH. However, polysomnographic data are not yet sufficient to explain pathophysiological mechanisms and find relevant diagnostic markers during pregnancy.

[Maternal diaphragmatic hernia during pregnancy: report of two cases]. / Hernie diaphragmatique maternelle pendant la grossesse: a propos de 2 cas.

We report two cases of maternal diaphragmatic hernia during pregnancy. Diaphragmatic hernia is an unusual and severe disease. Maternal and fetal prognosis are threatened. Diagnosis is uncertain when confronted to respiratory and digestive symptoms without any specificity. The chest X ray is the first exam to perform. The objective of this work is to discuss the management of such a pathology in terms of ways of delivery and surgical cure of hernia.

Biological properties of acid etched titanium implants: effect of sandblasting on bone anchorage.

The SLA (sandblasted with large grit and acid etched) surface is a textured surface that has been documented to lead to a rapid and strong implant fixation. The purpose of the present study was to determine the contribution of sandblasting in addition to etching to implant anchorage. It was also aimed to determine if the pits carved during etching alone have a bone-interlocking capacity that leads to microanchorage between the implant and bone. SLA implants and machined-and-acid-etched (MA) implants were placed in the maxilla of Land Race pigs. After 10 weeks of healing, they were reverse torqued. The reverse torque of the SLA and MA implants was 157.29 +/- 38.04 N cm and 105.33 +/- 25.12 N cm, respectively. Sandblasting increased bone anchorage by 49.3%; the difference was statistically significant (p =.028). Bone was found attached to both surfaces; bone ingrowth was found in the pits of both surfaces. It is suggested that the two surfaces are able to generate bone interlocking and mechanical coupling at the interface. When finite-element modeling is performed with these surfaces, it is suggested that the bound mode be used instead of the slip mode.

[Survey of the practice of cervical ripening and labor induction in France]. / Enquête des pratiques de maturation du col et de déclenchement du travail en France.

OBJECTIVES: Labor induction is a widespread medical practice in France. The medical or obstetric indications for induction as well as the protocols used probably vary from one maternity to another. The objective of this national survey was to describe current medical practices and procedures in France, regarding labor induction and cervical ripening, eight years after the national consensus on labor induction management. A second objective was to assess mothers' opinion on the induction of their labor/level of satisfaction on their childbirth experience. MATERIALS AND METHODS: The sample of maternities was randomly extracted from a list published by the French Ministry of Health. Sampling was performed according to maternity size, geography, and private vs public. Medical information was collected on consecutive labor induction cases in each maternity. Mother's opinions were estimated through a score based on the validated Labour Agentry Scale. RESULTS: Within the 38 maternities included, 21 (55.3%) were public, and 17 (44.7%) private. 1192 women were included in this study and 1090 (91.4%) answered the questionnaire on level of satisfaction. Global rate of elective induction (no medical or obstetric indication) was 24.8% (n=295). Prostaglandins are almost as widely used as oxytocin (45.8% and 47.7% of total labor inductions, respectively). Mostly used methods of delivering prostaglandin are intravaginal (27.1%), controlled-release pessaries (10.2%) and intracervical (8.1%). Among the elective inductions, an important rate of unfavorable cervix was found (n=81, 27.5%) as well as a quite high level of use of prostaglandins (n=51, 17.3%). The statistically independent criteria linked to a high satisfaction score are an older age (OR=1.58; CI 95% [1.80-3.33]), an elective induction (OR=2.44; IC 95% [1.80-3.33]) and a favorable cervix (OR=1.47; [1.08-1.98]). CONCLUSION: The use of prostaglandins in labor induction and cervical ripening is now widespread in France. This technique is not always used in accordance with available scientific data. These results should lead health professionals to set up an evaluation process for their practices, when these are not based on clear scientific evidence.

Pre-clinical study of the epinephrine-cisplatin association for the treatment of intraperitoneal carcinomatosis.

We have previously shown that intraperitoneal (i.p.) epinephrine enhances tumour penetration and anti-cancer activity of i.p.-administered cisplatin in rats with peritoneal carcinomatosis. Here, we show a direct correlation between the i.p. epinephrine concentration and cisplatin accumulation in rat peritoneal tumour nodules up to a concentration of 5 mg/l. This concentration leads to a maximal 3.7-fold increase of tumour platinum content and a maximal vasoconstriction of the peritoneal and tumour superficial microcirculation when registered by a laser doppler probe. Further, epinephrine half-life was 20.8+/-3.6 min in the peritoneal cavity of two laparotomized pigs. In these animals, epinephrine plasma concentration, heart rate and systolic blood pressure were dependent on the intraperitoneal dose of epinephrine, and life-threatening signs were not observed in either animal. In conclusion, a 5 mg/l concentration of epinephrine could be safely maintained in peritoneal fluid by regular replacement. This concentration is sufficient to maintain a constant vasoconstriction of the peritoneal and tumoral microvascular bed, and enhance the slow diffusion of cisplatin into peritoneal tumour nodules in the course of per-operative intraperitoneal chemotherapy.

[Torsion of the accessory spleen: an atypical etiology for acute abdomen]. / Torsion de rate accessoire: une étiologie de syndrome péritonéal bien atypique.

The accessory spleen is often a incidental discovery. The accessory post-accidental spleen are unusual. The torsion of a movable spleen is possible and represent about 0.2 to 0.3% of splenectomy. But the torsion of an accessory spleen is exceptional. A case of acute torsion of an accessory spleen is reported. In a 26-year-old women was admitted with acute abdominal pain. The abdominal ultrasound and the abdominal X-Ray are no specific. In the face of the acute pain, a laparoscopy was necessary. At laparoscopy, the patient was found to have torsion and infarction of an accessory spleen in the pelvis. The treatment was a splenectomy and the evolution was favorable.

Synthesis of 8-(omega-Hydroxyalkyl)-, 8-(omega-hydroxyalk-1-enyl)-, and 8-(omega-hydroxyalk-1-ynyl)adenines using the tert-butyldimethylsilyloxymethyl group, a new and versatile protecting group of adenine.

The synthesis of 12 analogues of adenine substituted at C-8 by an omega-hydroxyalkyl, omega-hydroxyalk-1-enyl, or omega-hydroxyalk-1-ynyl chain of various length has been carried out in five or six steps starting from adenine. The analogues were obtained using a new protecting group of adenine, the tert-butyldimethylsilyloxymethyl group. 9-tert-Butyldimethylsilyloxymethyl-adenine is more soluble than adenine in organic solvents. It was prepared regiospecificaly in two steps from adenine and was amenable to C-8 iodination under basic conditions and to subsequent introduction of the various carbon chains at C-8 by palladium-catalyzed cross-coupling reactions (Stille or Sonogashira). The protecting group was removed under acidic conditions, thus demonstrating its versatility.

Thromboembolic prophylaxis with danaparoïd (Orgaran) in a high-thrombosis-risk pregnant woman with a history of heparin-induced thrombocytopenia (HIT) and Widal's disease.

There is no consensus concerning thromboembolic prophylaxis in high-risk pregnant women with a previous history of heparin-induced thrombocytopenia. An alternative anticoagulant therapy is danaparoïd, whereas unfractioned and low-molecular-weight heparin therapy is contraindicated. We report a case of successful thrombosis prophylaxis using danaparoïd in a high-thrombosis-risk pregnant woman with a history of heparin-induced thrombocytopenia during a previous pregnancy and Widal's disease.