Pharmacokinetics of tiaprofenic acid in children after a single oral dose

Summary. Twelve healthy children in three age groups anaesthetized for minor surgery were given a single oral dose of tiaprofenic acid (3 mg · kg^–1) (TA). Seven blood samples and zero to 8 and 8 to 24 h urines were collected. TA concentrations in plasma and urine were measured by HPLC.No significant difference was found between the age groups in the kinetic parameters of TA and no correlation was found between these parameters and age; t_max=2.12h, C_max=8.78mg · l^–1, AUC_{(08 h)} 33.9mg · h · l^–1, AUC=39.3 mg · h · l^–1, t_1/2=2.35 h, V_z=0.319 l · kg^–1, CL=0.094 l · h^–1 · kg^–1. Renal clearance was 14 ml · h^–1. kg^–1. 33% of the TA dose was recovered in the 24 h urine, 48% of which was conjugated, whereas in adults, TA is only found in urine as conjugates.The apparent plasma clearance was significantly higher (56%) than in 12 healthy adults given 1.5 mg · kg^–1 TA. Volume of distribution and t_1/2 did not significantly differ between children and adults. Since no relationship has been established between plasma TA and either efficacy or toxicity, a different dose regimen cannot be recommended in 3–11 year-old children from that in adults.     

Correlation between mortality trends of ischaemic cardiopathy and some nutritional factors in Spain 1968–1986

After describing the evolution of mortality from ischaemic cardiopathy (IC) in Spain from 1951 to 1986, which is tending to stabilize in some age groups, and from cerebrovascular accidents (CVA), which is clearly declining, an attempt is made to relate these developments to the prevalence of the main risk factors (hypertension, cholesterol, tobacco) associated with IC and CVA. Certain advances, though of a limited number, have been made in recent years in the control of arterial hypertension in Spain, although campaigns on a national scale as in other countries have not been carried out. Regarding alimentary factors, there is an obvious increase in the consumption of food rich in proteins and animal fats, abandoning to a great extent the traditional Mediterranean diet, with health care action being limited to the improvement of nutrition education of the public. Furthermore, the consumption of tobacco has been increasing in Spain during the study period in spite of health legislation in force in recent years.It is therefore deduced that there is no obvious relationship between mortality due to IC and CVA and the prevalence of the main risk factors associated with these diseases, especially when taking into account that preventive actions on a public health level have been very limited.Corresponding author.     

Survival of Purkinje Cells in Cerebellar Cultures is Increased by Insulin-like Growth Factor I

Insulin-like growth factor I (IGF-I) is a trophic factor for both neurons and glia. Its presence in the developing and adult cerebellum suggests a role for this growth factor in this area of the brain. Recently, we have described the existence of an IGF-I-containing pathway in afferents of Purkinje neurons arising from the inferior olive. In addition, IGF-I receptors are present in the molecular layer of the cerebellar cortex. These observations prompted us to investigate whether the Purkinje cell is a target for IGF-I. Addition of IGF-I to rat cerebellar cultures produced a 7-fold increase in the number of Purkinje cells (calbindin-positive) together with an increase in the calbindin content of the cultures. IGF-I also doubled the number of surviving neurons and produced a moderate, non-significant increase in [³H]thymidine incorporation by the cultures. On the other hand, basic fibroblast growth factor (bFGF), which is also present in the cerebellum, produced a dramatic increase in both the proportion of astrocytes and in the mitotic activity of the cultures, without affecting neuron survival. We conclude that IGF-I is a specific promoter of Purkinje cell survival and that its effects differ from those produced by bFGF in fetal cerebellar cultures. These findings reinforce our hypothesis that the Purkinje cell is a target neuron for IGF-I action in the developing cerebellum.     

A training program on exclusive breastfeeding in maternity wards.

OBJECTIVES: To estimate whether a 3-day training program for health professionals was followed by changes in maternity ward practices and in the rate of exclusive breastfeeding. METHODS: A retrospective study in the maternity ward of a French university hospital involved two cross-sectional samples of 323 mother-infant pairs in 1997 and 324 in 2000. RESULTS: The rate of exclusive breastfeeding at discharge increased from 15.8% (12.0-20.2) in the before sample to 35.2% (30.0-40.6) in the after sample (P<0.01). This result persisted in the multivariable analysis [adjusted odds ratio, 2.74 (1.72-4.37)]. Infants in the before sample were less likely to be breastfed within 1 h of birth (9.2% vs. 16.9%, P=0.01), to room-in 24 h/day (56.6% vs. 72.6%, P<0.01), and were more likely to receive formula supplementation (77.6% vs. 54.0%, P<0.01). CONCLUSIONS: A training program for health professionals can be effective in improving maternity ward practices and increasing exclusive breastfeeding rate at discharge.     

Clinical evaluation of the simultaneous determination of tumor markers in fluid and serum and their ratio in the differential diagnosis of serous effusions.

We evaluated the diagnostic utility of simultaneous determination of 5 tumor markers, CEA, CA 125, CA 15-3, CA 19-9 and cytokeratin 19 (CYFRA 21-1), in fluid and serum from 101 patients, 52 with pleural effusion (22 malignant) and 49 patients with ascites (14 malignant). Tumor marker concentrations in fluid from patients with malignant effusions were significantly higher than those obtained in benign fluids or serum. However, there are two types of tumor markers: those released/secreted by normal mesothelia such as CA 125 and cytokeratin 19 (higher levels in benign fluids than in serum) and non-released/secreted tumor markers (low concentrations in benign fluids) such as CEA, CA 19-9 and CA 15-3. The fluid/serum (F/S) ratio showed better sensitivity with maximum specificity than a single determination in fluid for CEA, CA 15-3 and CA 19-9, but not for CA 125 and CYFRA. The combination of a F/S ratio greater than 1.2 and a cut-off of 5 ng/ml for CEA, 30 U/ml for CA 15-3 and 37 U/ml for CA 19-9 showed sensitivities of 58, 57 and 44%, respectively, and a specificity of 100%, with a combined sensitivity of 82% for overall effusions and 79% for fluids with negative cytology with a specificity of 100%. In conclusion, the use of the F/S ratio in nonsecreted tumor markers such as CEA, CA 19-9 and CA 15-3 improve the sensitivity and specificity and allow standardization of the cut-off.     

Multiscale Analogue Modelling of Clinching Process to Investigate Thickness Tolerance and Tool Misalignment

NEED—The effect of dimensional variability of sheet thickness (tolerance) and tool misalignment is poorly understood for the clinching process. Finite element analysis (FEA) is valuable but requires a lot of and is difficult to verify in this situation due to the asymmetrical geometry and nonlinear plasticity. OBJECTIVE—The objective of this work was to determine the effect of thickness tolerance, tool misalignment and sheet placement (top vs. bottom) in the clinching process, by use of analogue modelling with plasticine. METHOD—Experiments used a scaled-up punch and die, with plasticine as the analogue. Thickness tolerances were represented by sheet thicknesses of 11 and 7 mm, 12 and 8 mm, 8 and 12 mm and 13 and 9 mm for upper and lower sheets, respectively. Two types of lubricant were tested between sheets: glycerine and silicone oil. Angular variability was also introduced. Measured parameters were interlock (also called undercut) and neck thickness. Analogue results for deformation were compared with microscopy of metal clinching. FINDINGS—The results reveal that the multiscale analogue model is an efficient tool for studying the effect of dimensional deviation on a clinch joint. Thickness tolerance showed a critical relationship with interlock, namely a reduction to about half that of the nominal, for both maximum and least material conditions. Increased angular misalignment also reduced the interlock. Compared with glycerine, silicone oil tests showed reduced interlock, possibly the result of a lower coefficient of friction. ORIGINALITY—This work demonstrates the usefulness of analogue modelling for exploring process variability in clinching. The results also show that significant effects for sheet placement are ductility, lubricant (friction), thickness of samples and tool misalignment.     

Myosin detection in human myometrium with a monoclonal antibody

A monoclonal antibody was prepared from a mouse immunized with human gravid uterine myosin. This monoclonal antibody is specific for the myosin heavy chains of human smooth muscle as determined by radioimmunoassay and immunoblotting experiments. Frozen cryostat sections isolated from different uterine regions were studied by immunofluorescence in order to detect myosin distribution within cells of nongravid, gravid, and pathologic human uteri. Myosin was detectable in the cytoplasm of all uterine muscle cells. No fiber heterogeneity with regard to myosin distribution was detected among or within the different uterine regions, regardless of which physiologic or pathophysiologic situation was studied. A large increase in the cell size was observed during pregnancy. These preliminary observations suggest the value of further production of monoclonal antibodies specific for the different putative molecular variants of uterine myosin and their potential use in identifying individual cells containing different myosin variants.     

Paraaortic sentinel lymph node detection in intermediate and high-risk endometrial cancer by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR)

ObjectiveWe aimed to evaluate the accuracy of sentinel lymph node (SLN) mapping with transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) to detect lymph node (LN) metastases, in patients with intermediate and high-risk endometrial cancer (EC), focusing on its performance to detect paraaortic involvement.MethodsProspective study including women with preoperative intermediate or high-risk EC, according to ESMO-ESGO-ESTRO consensus, who underwent SLN mapping using the TUMIR approach. SLNs were preoperatively localized by planar and single photon emission computed tomography/computed tomography images, and intraoperatively by gamma-probe. Immediately after SLN excision, all women underwent systematic pelvic and paraaortic lymphadenectomy by laparoscopy.ResultsThe study included 102 patients. The intraoperative SLN detection rate was 79.4% (81/102). Pelvic and paraaortic drainage was observed in 92.6% (75/81) and 45.7% (37/81) women, respectively, being exclusively paraaortic in 7.4% (6/81). After systematic lymphadenectomy, LN metastases were identified in 19.6% (20/102) patients, with 45.0% (9/20) showing paraaortic involvement, which was exclusive in 15.0% (3/20). The overall sensitivity and negative predictive value (NPV) of SLNs by the TUMIR approach to detect lymphatic involvement were 87.5% and 97.0%, respectively; and 83.3% and 96.9%, for paraaortic metastases. After applying the MSKCC SLN mapping algorithm, the sensitivity and NPV were 93.8% and 98.5%, respectively.ConclusionThe TUMIR method provides valuable information of endometrial drainage in patients at higher risk of paraaortic LN involvement. The TUMIR approach showed a detection rate of paraaortic SLNs greater than 45% and a high sensitivity and NPV for paraaortic metastases in women with intermediate and high-risk EC.