Evaluation of community pharmacist follow-up supported by the use of healthcare technology for type 2 diabetes patients.

Background: Prevalence of type 2 diabetes is high in Belgium (estimated at over 10%, 1 patient out of 3 being unaware of their diagnosis). Management based on a change of lifestyle and the adoption of health-promoting behaviors, supplemented when needed with drug treatment, prevents complications, improves the patient's quality of life and reduces mortality. Multidisciplinary patient support is essential. In this, pharmacists have a key role, e.g. through therapeutic patient education activities, in which they are increasingly involved. Moreover, research suggests that the use of mobile technologies can be a useful tool for helping patients with their daily life and disease management. Objectives: This study aims at exploring the benefits of community pharmacist follow-up supported by the use of mobile technologies in the monitoring of individuals with type 2 diabetes. The presented intervention aimed to reinforce the patients' willingness to actively participate in the management of their disease and to adopt favorable health behaviors, in order to increase their level of medication adherence. Methods: A quantitative quasi-experimental study was conducted in community pharmacies throughout Belgium over a 6-month period with 3 data collection periods (before, during and after the intervention). Primary outcomes, related to the level of medication adherence, and secondary outcomes, considered as markers of the patient's overall health, were analyzed. In addition, qualitative data concerning participants' opinions on their experience were collected. Results: 66 patients participated in the study, with 50 remaining after 3 months and 46 completing the entire study. Statistical analyses did not show an improvement in the level of medication adherence. This parameter was high from the beginning, reflecting patients with controlled diabetes. However, statistically significant results were observed for systolic blood pressure and waist circumference (both improved), while other outcomes showed a positive trend or remained stable. Patient follow-up by the pharmacist was a positive experience for both parties which noted their interest and satisfaction for the project. Conclusions: Although clinical results are not conclusive, patients were motivated and the attrition rate was low. Participants showed their interest in participating in this kind of project, opening up opportunities for further studies in the community pharmacy setting. As front-line health professionals, community pharmacists certainly have a key-role to play in therapeutic patient education and mobile technologies could be additional tools in this process.

Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease.

The prognosis of autosomal recessive polycystic kidney disease is known to correlate with genotype. The presence of two truncating mutations in the PKHD1 gene encoding the fibrocystin protein is associated with neonatal death while patients who survive have at least one missense mutation. To determine relationships between genotype and renal and hepatic abnormalities we correlated the severity of renal and hepatic histological lesions to the type of PKHD1 mutations in 54 fetuses (medical pregnancy termination) and 20 neonates who died shortly after birth. Within this cohort, 55.5% of the mutations truncated fibrocystin. The severity of cortical collecting duct dilatations, cortical tubule and glomerular lesions, and renal cortical and hepatic portal fibrosis increased with gestational age. Severe genotypes, defined by two truncating mutations, were more frequent in patients of less than 30 weeks gestation compared to older fetuses and neonates. When adjusted to gestational age, the extension of collecting duct dilatation into the cortex and cortical tubule lesions, but not portal fibrosis, was more prevalent in patients with severe than in those with a non-severe genotype. Our results show the presence of two truncating mutations of the PKHD1 gene is associated with the most severe renal forms of prenatally detected autosomal recessive polycystic kidney disease. Their absence, however, does not guarantee survival to the neonatal period.

Urinary excretion of dietary contaminants in horses.

REASONS FOR PERFORMING STUDY: Presence of drugs is completely prohibited in post racing urine samples by most of racing and competition authorities, even if environmental contamination might occur. OBJECTIVES: To assess the daily dose of several contaminants absorbed through the diet that would result in detectable concentrations in urine. METHODS: Caffeine, theobromine, theophylline, atropine, scopolamine, bufotenine, DMT or morphine were administered orally to 6 horses, in different dosages, for 3 days before their urine was sampled for regular anti-doping tests. RESULTS: Theobromine, theophylline, bufotenine and morphine daily intake >10 mg, 2 mg, 10 mg and 200 microg, respectively, by a performance horse, were found to result in detectable urinary concentrations. At the 2 tested doses, atropine (5 and 15 mg) and dimethyltryptamine (3 and 10 mg) were not detected in urine. For caffeine and scopolamine, even the lowest dosage tested (5 mg/horse/day and 2 mg/horse/day respectively) induced detectable concentrations of the molecule in urine. CONCLUSIONS: Horses fed dietary contaminants, even at level much below the effective dosage, may be positive to antidoping urine analysis. Further research is needed to gain more confident results on a daily safe intake for caffeine and scopolamine. POTENTIAL RELEVANCE: Selection of feed materials appears to be of great importance to prevent non voluntary positive result to anti-doping tests.

Lipoma arborescens of the knee: report of a case managed by arthroscopic synovectomy.

We report a case of lipoma arborescens treated with an arthroscopic procedure. Lipoma arborescens is an uncommon pseudo-tumoral synovial lesion usually located in the suprapatellar pouch of the knee. This diagnosis should be considered, particularly in patients with chronic joint effusion. Magnetic resonance imaging confirms the lipomatous nature of the synovial proliferation. When limited to the anterior compartment of the knee, lipoma arborescens can be treated by arthroscopic synovectomy.

Autofluorescence spectroscopy of malpighian epithelial cells, as a new tool for analysis of cervical cancer precursors.

A spectroscopic analysis of autofluorescence was investigated within the cell cytoplasm from cervical malpighian epithelia prepared on Thin-Prep smears. Autofluorescence emission spectra from 22 cervix were analyzed by microspectrofluorometry under a 363 nm laser excitation. Among the analyzed cervix, 6 were in normal limits, 6 in inflammatory limits, 5 were evocative of Low-Grade Squamous Intraepithelial Lesions (LGSILs) and 5 were evocative of High-Grade Squamous Intraepithelial Lesions (HGSILs). Cytoplasmic emission intensities at 450 nm of cells from inflammatory, LGSIL and HGSIL cervix were equivalent and were 3-fold higher than from normal cervix. All smears presented a two-fold lower autofluorescence emission in the cytoplasm than in the nucleus. The spectral profile analysis allows the discrimination of cells from inflammatory, LGSIL and HGSIL cervix. The 525/425 nm emission ratios were 0.75+/-0.1, 0.96+/-0.04 and 1.2+/-0.1 for inflammatory, LGSIL and HGSIL, respectively. We suggest that smears of normal, inflammatory, LGSIL and HGSIL cervix could be discriminated by the analysis of the 450 nm emission intensity and 525/425 nm emission ratios from cells of malpighian epithelia.

Comparison between two models of cooling surfaces using blowing.

To protect surfaces against high temperatures, the blowing through a porous material is studied. The geometry is that of a circular cylinder in cross-flow and the effectiveness of the blowing for the thermal protection is numerically investigated. Two models are developed for the blowing simulation and comparisons are made with experimental data obtained in a heated wind-tunnel. It is shown that the blowing strongly affects the dynamical and thermal profiles over the surface, thickening the boundary layers and decreasing the external transfer coefficients. It results in a lower viscous drag and thermal stress. The wall temperature dramatically decreases with blowing and the heat flux is also affected.

Distribution of gacyclidine enantiomers after experimental spinal cord injury in rats: possible involvement of an active transport system.

The pharmacokinetics of gacyclidine enantiomers, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, were studied in plasma and spinal cord extracellular fluid (ECF) after experimental spinal cord injury in rats. Spinal cord trauma was produced by introducing an inflatable balloon in the dorsal subdural space. Upon implantation of microdialysis probes in spinal cord (T9) and intravenous (iv) bolus administration of (+/-)-gacyclidine (2.5 mg/kg), concentrations in plasma and ECF were monitored over 5 h and analyzed by a stereospecific gas chromatography-mass spectrometry (GC-MS) assay. In plasma, concentrations of (+)-gacyclidine were approximately 25% higher than those of (-)-gacyclidine over the duration of the experiment and decayed in parallel (t(1/2 alpha) approximately 7 min; t(1/2 beta) approximately 90 min) with no significant difference between the two enantiomers. Clearance (CL) and volume of distribution (Vd) of (-)-gacyclidine were approximately 20% higher than those of its optical antipode (CL: 285 versus 236 mL. kg(-1). min(-1); Vd(beta): 39.3 versus 31.2 l/kg). Protein binding (approximately 91%) was not stereoselective. In spinal cord ECF, both enantiomers were quantifiable within 10 min after drug administration, and their concentration remained stable over the duration of the experiment in spite of changing blood concentrations. Repeated iv bolus injections of gacyclidine did not modify these profiles. Areas under the curves (AUCs) of concentration in ECF versus time were similar for both enantiomers and not correlated with AUCs in plasma. Penetration of (-)-gacyclidine was, however, significantly higher (approximately 30%) than that of (+)-gacyclidine. In summary, the disposition of gacyclidine enantiomers is stereoselective. Both enantiomers exhibit a high affinity for spinal cord tissue, and the drug exchange between plasma and spinal cord ECF involves an active transport system. These findings contribute to the explanation of the discrepancy between drug concentrations in plasma and spinal cord ECF.

Influence of schedule of administration on methotrexate penetration in brain tumours.

The influence of the administration schedule (intravenous (i.v.) bolus versus i.v. infusion) on the pharmacokinetics of methotrexate (MTX) in plasma and extracellular fluid (ECF) of a brain C6-glioma was investigated in rats. MTX concentrations were determined by high performance liquid chromatography (HPLC)-ultraviolet radiation (UV). MTX (50 mg/kg) was administered by i.v. bolus or i.v. infusion (4 h). Concentration-time profiles were fitted to a two-compartment open model. Maximum MTX concentrations ranged between 178 and 294 microgram/ml (i.v. bolus), and between 11 and 24 microgram/ml (i.v. infusion) in plasma. MTX rapidly entered the tumour tissue although its concentrations in the ECF were much lower than those observed in plasma for both modes of administration. In spite of an important interindividual variability, AUC(ECF) was approximately 5-fold higher and mean MTX penetration in tumour ECF (AUC(ECF)/AUC(Plasma)) was approximately 3-fold higher after i.v. bolus than after i.v. infusion administration. These results indicate that i.v. bolus administration schedules promote MTX delivery in brain tumour tissue.

Distribution of gacyclidine enantiomers in spinal cord extracellular fluid.

PURPOSE: Determination of the pharmacokinetics of gacyclidine enantiomers, a non-competitive NMDA antagonist, in plasma and spinal cord extracellular fluid (ECF) of rats. METHODS: Implantation of microdialysis probes in spinal cord (T9). Serial collection of plasma samples and ECF dialysates over 5 hours after IV bolus administration of (+/-)-gacyclidine (2.5 mg/kg). Plasma protein binding determined in vivo by equilibrium dialysis. Chiral GC/ MS assay. RESULTS: Plasma concentrations of (+)-gacyclidine were approximately 25% higher than those of (-)-gacyclidine over the duration of the experiment in all animals. Plasma concentrations decayed in parallel in a biphasic manner (t1/2alpha approximately 9 min; t1/2beta approximately 90 min) with no significant difference between enantiomers. Clearance and volume of distribution of (-)-gacyclidine were approximately 20% higher than those of its optical antipode (CL: 248 vs 197 ml.kg(-1)x min(-1); Vdbeta: 31.6 vs 23.5 1/kg). Protein binding (approximately 90%) was not stereoselective. Both gacyclidine enantiomers were quantifiable in spinal cord ECF 10 min after drug administration and remained stable over the duration of the experiment in spite of changing blood concentrations. Penetration of (-)-gacyclidine was significantly higher (approximately 40%) than that of (+)-gacyclidine in all animals. Yet, exposure of spinal cord ECF was similar for both enantiomers, and not correlated with plasma AUCs. CONCLUSIONS: The disposition of gacyclidine enantiomers is stereoselective. Both enantiomers exhibit a high affinity for spinal cord tissue and their distribution may involve a stereoselective and active transport system. This hypothesis could also explain the discrepancy between drug concentrations in plasma and spinal cord ECE

Pharmacokinetics of methotrexate in the extracellular fluid of brain C6-glioma after intravenous infusion in rats.

PURPOSE: Establishment of the pharmacokinetic profile of methotrexate (MTX) in the extracellular fluid (ECF) of a brain C6-glioma in rats. METHODS: Serial collection of plasma samples and ECF dialysates after i.v. infusion of MTX (50 or 100 mg/kg) for 4 h. HPLC assay. RESULTS: Histological studies revealed the presence of inflammation, edema, necrosis, and hemorrhage in most animals. In vivo recovery (reverse dialysis) was 10.8 +/- 5.3%. MTX concentrations in tumor ECF represented about 1-2% of the plasma concentrations. Rapid equilibration between MTX levels in brain tumor ECF and plasma. ECF concentrations almost reached steady-state by the end of the infusion (4 h), then decayed in parallel with those in plasma. Doubling of the dose did not modify MTX pharmacokinetic parameters (t1/2alpha, t1/2beta, MRT, fb, Vd, and CL(T)), except for a 1.7-fold increase of AUC(Plasma) and a 3.8-fold increase in AUC(ECF), which resulted in a 2.3-fold increase in penetration (AUC(ECF)/AUC(Plasma)). In spite of an important interindividual variability, a relationship between MTX concentrations in plasma and tumor ECF could be established from mean pharmacokinetic parameters. CONCLUSIONS: High plasma concentrations promote the penetration of MTX into brain tissue. However, free MTX concentrations in tumor ECF remain difficult to predict consistently.

Investigation of nonimmune hydrops fetalis: multidisciplinary studies are necessary for diagnosis--review of 94 cases.

This review of 94 cases of nonimmune hydrops fetalis (NIHF) over a 10-year period was undertaken to evaluate the frequency of this pathology among fetal and infant deaths and to determine the most common likely etiologies in a northeastern region of France. NIHF represented 6% of the fetal deaths examined in our laboratory. The combination of findings from morphologic examination of the placenta and fetus with the results of microbiological and cytogenetic investigations (conventional cytogenetic study, fluorescent in situ hybridization [FISH], or DNA ploidy image analysis) led to an etiologic diagnosis for NIHF in two-thirds of the cases and suggested a diagnosis in an additional 23% of cases. The most common causes of NIHF were chromosome abnormalities (33%), infections (16%), and cardiac pathology (13.8%). The detection of a cause for NIHF is important for genetic counseling and management of subsequent pregnancies. Our experience suggests that a diagnosis is possible in a large majority of NIHF when obstetricians and pathologists carefully coordinate the management of prenatal and postnatal investigations and when new techniques, such as molecular biology and DNA quantification, are used.

Neonatal hip: from anatomy to cost-effective sonography.

Therapeutic success in treating congenital dysplasia of the hip is associated with early diagnosis, but the specific neonatal anatomy makes screening difficult. The purpose of this study was to determine whether this specific neonatal anatomy is taken into account by current ultrasound (US) techniques. Anatomic studies were performed on 22 hips, US examinations on 7750 neonatal hips; 2370 untreated hips were reexamined at 1 month by US and at 3 months by X-ray. The transformation of the neonatal cartilaginous acetabulum into an osseous cavity is dependent on harmonious metaphyseal growth and a properly seated femoral head. Defects in the acetabular roof, together with displacement of the femoral head, cause an abnormal anatomical relationship which leads to further deformities. The described sonographic techniques give only partial information on these specific abnormalities. The sonographic monoplanar methods as used in Graf's technique, which relies largely on acetabular development, lead to difficulties in assessing posterior coverage of the femoral head and difficulties in assessing alignment of the metaphyseal weight-bearing surface with the femoral head. Combining Graf's morphological analysis with Novick's dynamic technique enables one to more accurately define the relationship of the femoral head and the acetabulum and increases the reliability and predictive value of the examination, while reducing the number of doubtful cases. This makes screening cost effective.

Normal vas deferens in fetuses with cystic fibrosis.

PURPOSE: Infertility in patients with cystic fibrosis has been attributed to the congenital bilateral absence of the vas deferens. We studied the vas deferens in cystic fibrosis fetuses to determine whether this condition could be related to primary developmental abnormalities or to secondary obstructions. MATERIALS AND METHODS: Two cystic fibrosis male fetuses, with deltaF508+/+ and deltaF508/G542X genetic mutations, were examined after abortion at 12 and 18 weeks, respectively. The lumens of the vas deferens were measured using histological serial sections in the 2 cystic fibrosis fetuses and in 6 control fetuses. RESULTS: The vas deferens of cystic fibrosis and control fetuses showed a similar development. The diameters of the lumens were smaller at the extremities than in the medial part of the duct in cystic fibrosis and in control fetuses. No epithelial necrosis, focal dilatation or fibrous stenosis could be detected at any age. Secretions were observed in the lumen of the vas deferens of the homozygous fetus, but no obstruction was detected. CONCLUSIONS: The normal organogenesis of the vas deferens, the presence of secretions filling the lumen of the deltaF508 +/+ fetus and the high proportion of normal ducts reported in prepubertal male cystic fibrosis patients suggest a mechanism of luminal obstruction resulting in duct atrophy and infertility in male adults with cystic fibrosis. The term "atresia" or "inspissation" should be used in cases of congenital bilateral absence of the vas deferens associated with cystic fibrosis mutations, whereas the term "agenesis" should be used for cases of congenital bilateral absence of the vas deferens associated with urogenital abnormalities in which regional defects occur during organogenesis.

Anatomic study of the pre- and neonatal hip. Physiopathologic considerations on dysplasia and congenital dislocation of the hip.

Therapeutic success in dysplasia and congenital dislocation of the hip depends on an early diagnosis. The physiopathology remains very debatable and several concepts are propounded. For a better physiopathologic understanding, the authors have carried out a study of the morphology and development of 22 pre- and neonatal hips. At first, the acetabulum is cartilaginous and distorted by the moving femoral head; this acetabulum is histologically affected by the femoral pressure. The pathologic hip is characterized by defective posterior bony coverage of the femoral head by the acetabulum. The acetabulum ossifies during the 3 months following birth, forming a cup-like cavity under the pressure of the femoral head. Therefore, neonatal screening tests such as sonography must take place in the first weeks of life.

Effects of verapamil and S9788 on MDR-1 mRNA expression studied by in situ hybridization.

The effects of Verapamil and S9788 (triazineaminopiperidine), a new modulator of multidrug resistance, on mdr-1 mRNA expression were determined using in situ hybridization. S9788 appeared to be a better reversal drug by strongly decreasing drug efflux. However, Verapamil only decreased mdr-1 mRNA expression in Human erythroleukemic resistant cells (ADM/k562) and in Human lymphoblastic resistant cells (VLB/CEM). This effect occurred in all Verapamil-treated resistant cells with no difference between cell subpopulations. These results were confirmed by slot-blot experiments. In conclusion, S9788 and verapamil effects are comparable overall although the mechanisms responsible for this resistance modulation are not strictly identical.

Expression and localization of epidermal growth factor, transforming growth factor-alpha, and localization of their common receptor in fetal human lung development.

Transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), and their common EGF receptor have been shown to be involved in cell proliferation and lung maturation. The aim of the study was to determine the site of production of TGF-alpha and EGF mRNA and the cellular distribution of TGF-alpha/EGF proteins and EGF receptor, in fetal human lung. By using in situ hybridization with 35S-labeled cDNA probes in frozen sections from eight lungs from fetuses ranging from 12 to 33 wk of gestation, TGF-alpha and EGF mRNA transcripts appeared to be confined to the mesenchymal cells and mainly found in the dense connective tissue along the pleura, bronchi, and large vessels, but undetected in bronchial epithelial cells. The streptavidin-biotin immunoperoxidase method, applied to paraffin-embedded specimens from 39 fetuses ranging from 10 to 41 wk, showed that TGF-alpha, EGF, and EGF receptor exhibited a similar cellular distribution during the whole period of gestation. They were detected in the undifferentiated cells of the airway surface epithelium, mesothelial cells, smooth muscle, and a few mesenchymal cells, as early as 10 wk. After 12 wk, the immunoreactivity was strong in the ciliated, secretory, and basal cells, and in growing glands along the large airways, but proved lower in the distal airways. After 24 wk, the immunoreactivity remained in the airway epithelium, but was mainly localized in the apical domain of ciliated cells, in alveolar cells, and in the serous cells of the glands. The presence of TGF-alpha, EGF, and EGF receptor during the whole period of fetal lung development suggests that these factors are not only mitogenic, but can also be involved in epithelial maturation, through paracrine secretion, as most TGF-alpha and EGF mRNA transcripts are expressed in mesenchymal cells.

Meconium ileus and intestinal atresia in fetuses and neonates.

A collaborative study was performed to determine the different types and mechanisms of intestinal abnormalities during gestation. Cases had to fulfill one or more of the following three criteria: (1) meconium ileus, (2) intestinal stenosis or atresia, and (3) meconium peritonitis. Esophageal atresia, anorectal atresia, and abdominal wall defects were excluded. One hundred two cases were reviewed from the autopsies of 42 induced abortions, 22 stillborns, and the surgical findings in 38 neonates. Meconium ileus was detected mainly during the second trimester (28/38), and was associated with cystic fibrosis (15), fetal blood deglutition (4), infection (6), or multiple-abnormalities (10), in which three chromosomal aberrations were found. Intestinal stenosis or atresia was more commonly detected during the third trimester of gestation (46/56). Sixteen of the 30 duodenal malformations were associated with trisomy 21, whereas in the 26 small intestinal atresias, signs of distress or ischemia were most frequently detected. Only 8 of 25 meconium peritonitis cases were isolated. A total of 20 cystic fibrosis cases could be proved. In this series, functional abnormalities were observed predominantly in the second trimester and associated mainly with cystic fibrosis or amniotic fluid abnormalities. Anatomic lesions were commonly detected later on and associated with ischemic conditions, chromosomal aberrations, and even cystic fibrosis.