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.

Expression and immunohistochemical localization of laminin and type IV collagen in developing human fetal tracheal glands.

The expression and distribution of laminin and type IV collagen, two major components of the basement membrane, were investigated at the epithelio-mesenchymal interface of the human developing tracheal glands from 10 to 37 weeks of gestation. The localization of these molecules was assessed by indirect immunoperoxidase and indirect immunofluorescence staining and correlated to morphogenesis and epithelial cell differentiation. Laminin and type IV collagen were detected as early as 10 weeks of gestation in a continuous, linear pattern in the basement membrane surrounding the epithelial tracheal tube. By 12 weeks of gestation the basement membrane developed large openings at the tips of the budding glands beneath poorly differentiated cells, concomitant with the onset of morphogenetic movements. The remodeling of the basement membrane led to branching epithelial morphogenesis. The maturation and the functional differentiation of the secretory cells appeared later in the epithelium, when the basement membrane was strongly labeled with both anti-laminin and anti-type IV collagen antibodies, after 24 weeks of gestation. At this time the basement membrane became regular and thick and the maturation of serous cells increased progressively. These results suggest that the remodeling of the basement membrane takes place very early during gestation and that the morphogenesis and the maturation of the tracheal glands are rapidly achieved in humans.

In vivo localization of the insulin-like growth factors I and II (IGF I and IGF II) gene expression during human lung development.

The insulin-like growth factors I and II (IGF I and IGF II) are synthesized in many organs during human development and are involved in the growth and differentiation of tissues. Correlations between lung growth and maturation and the local production of IGFs have been poorly explored in humans. Using in situ hybridization we localized the synthesis of IGFs in the human fetal respiratory tract over an extended period of the gestation and we demonstrated time dependent changes. IGF mRNAs were expressed throughout gestation with a clear predominance of IGF II and a decreasing expression of both IGFs after the 20th week of gestation. They were mainly detected in the mesodermal-derived components of the respiratory tract, especially in the undifferentiated mesenchyme of the lung buds up to 20 weeks of gestation. At this time the local production of collagen and the proliferation of adjacent epithelial cells were predominant features. Later, mesenchymal hybridization decreased. Weak epithelial hybridization was observed during the first stages of growth and progressively decreased when the epithelium underwent maturation: early in the trachea, later in the distal lung buds. A consistent expression of IGF II, but not IGF I, in the endothelium, throughout gestation, was also observed. The IGFs may act on the near epithelial cell proliferation in both autocrine and paracrine ways. They may also stimulate the maturation of the connective tissue. This endogenous production of growth factors may play a role in the somatic growth during prenatal life.

Reliability of clinical criteria for the diagnosis of dementia. A longitudinal multicenter study.

The reliability of the clinical diagnosis of dementia was estimated by comparing the diagnosis made at 1-year intervals on 55 consecutive subjects with suspected cognitive impairment seen at three different centers by neurologists and gerontologists. The diagnosis was based on history and clinical examination, the criteria of the Diagnostic and Statistical Manual of Mental Disorders (revised ed 3), the Modified Ischemic Score, and a computed tomographic scan. Fifty-two of 55 subjects were given the same diagnosis a year later indicating a reliability of 95%. The study shows that a diagnosis of dementia established by simple clinical criteria comparable to the NINCDS/ADRDA criteria affords sufficient reliability to allow the comparability of groups at different centers for purposes of research, including research on the evaluation of the efficacy of pharmacologic treatment.

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.

Galactose alpha 1-3 galactose and anti-alpha galactose antibody in normal and pathological pregnancies.

The galactose alpha 1-3 galactose (Gal alpha 1-3 Gal) residue is a carbohydrate widely distributed in many non-human mammals. Since Gal alpha 1-3 Gal residues are described on the cell surface of tumor cells, we have examined the possibility of their expression on human trophoblastic cells at different stages of placental implantation and in various pregnancy-associated conditions. Using immunohistochemical methods, Gal alpha 1-3 Gal was demonstrated on interstitial and vascular trophoblast during pregnancy. For villous trophoblast, the staining disappeared in second trimester pregnancies. The density of staining for Gal alpha 1-3 Gal was increased in highly invasive trophoblast (mole and choriocarcinoma) and decreased in poorly invasive specimens (spontaneous abortion, XO monosomia). No cells displaying Gal alpha 1-3 Gal at their surface were identified in some segments of spiral arteries from pre-eclamptic women. The anti-Gal antibody titer increased in the first trimester of pregnancy and in the sera of pre-eclamptic and eclamptic patients. These findings suggest that Gal alpha 1-3 Gal residues could be considered as markers for trophoblast invasive capacity and that the binding of maternal anti-Gal antibodies to the trophoblast could contribute to limit trophoblastic invasion and thus participate to the immunological control of implantation.

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.

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.

Effect of a methionine-enkephalin analog in Huntington's disease.

The methionine-enkephalin analog FK 33-824 was administered intravenously to 12 patients with Huntington's disease in a crossover double-blind study. The abnormal involuntary movements (AIM) were not improved after administration of 0.5 mg of FK 33-824. A significant decrease in the AIM score was observed only 150 and 180 min after injection of high doses (2 mg); however, the difference between the active drug and the placebo was never statistically significant. These results are discussed in terms of experimental data suggesting a relationship between methionine-enkephalin and dopamine neurons in the brain and of methionine-enkephalin deficiency in the brain of patients with Huntington's disease.

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.

Determination of reliable histological features associated with early triploidy using DNA image cytometry.

In order to determine reliable histological features characterizing triploidy, the following features were examined and graded by three pathologists on 46 early abortion specimens: hydropic swelling of the villi, cisterns, villous scalloping, trophoblastic hyperplasia with syncytial vacuolization, single cytotrophoblastic cells in villous stroma, trophoblastic inclusions, microcalcifications and fibrosis. At the same time, the DNA content of the 46 specimens was quantified cytophotometrically using the CAS 200 image analyzer, in order to confirm or not the diagnosis of triploidy. Triploidy was confirmed in 45.7%, and in the triploid group, the grading of three features differed significantly from the non triploid group i.e. cisterns (p < 0.001), trophoblastic hyperplasia (p < 0.05) and trophoblastic inclusions (p < 0.05). Using these three features we were able to give a triploid score per slide which represents the sum of the grades of each of these three features. The minimum score obtained was 0, the maximum was 6. The average of these scores in the triploid group was 3.095, and 1.45 in the non triploid group (p < 0.001). This scoring method on the three significant features (cisterns, trophoblastic hyperplasia and trophoblastic inclusions) appears to be useful to classify an abortion specimen as triploid or not, and to select the specimens for which a DNA quantification may be necessary.

Spontaneous abortions during the second trimester of gestation.

To determine the factors causing spontaneous abortions, 422 consecutive second-trimester abortions and the corresponding clinical data were studied prospectively. All of the fetuses and placentas were referred to a single pathologist and microbiological cultures were carried out in 205 of these cases. One hundred twenty-one medically included abortions were used as controls for the interpretation of the investigations relating to infection. According to the degree of maceration, two groups could be isolated and seemed to represent different diseases and mechanisms of spontaneous abortions. In the largest group (78.6%) without long intrauterine retention, one explanation could be given for 85% of these cases. Ascending infections occurred through unruptured membranes, whether or not they were associated with obstetric complications. The second group (21.4%) included severely macerated fetuses where a cause of death could only be determined in 44% of the cases that had a predominance of fetal abnormalities and maternal factors.

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.

[Mucin histochemistry of the digestive tract in the human fetus]. / Histochimie des mucines du tube digestif chez le foetus humain.

Mucin secretion was studied in the gastric, intestinal, left colic and/or rectal mucosa of 42 human fetuses ranging in age from 10 to 41 weeks of gestation (menstrual age). Several histochemical techniques were used at different pH to demonstrate neutral mucins, sialomucins and sulphomucins (Periodic Acid Shiff (PAS) with and without amylase, Alcian Blue (BA) pH 2.5, pH 1 with and without hyaluronidase, BA/PAS pH 2.5 and High Iron Diamine (HID)/BA). The gastric mucosa showed mixed neutral/acid secretions during the second term. The neutral mucins increased during the 3rd term when acid mucins fell and represented only 20 percent of the secretions by the end of gestation, as during the neonatal period. These mixed secretions closely reassembled the intestinal metaplasia described in inflammatory or tumoral lesions of the stomach. The intestinal mucosa secreted mucins as early as 10 weeks before the gastric and rectal mucosa. There were neutral and acid mucins, but unlike in adults, the sulphomucins were secreted by the goblet cells of the villous and crypt epithelia. The secretions of the rectal mucosa were acid and the sulphomucins increased in quantity from 14 to 26 weeks of gestation. The HID positive sulphomucins diffused into the meconium, and probably modified the physical and chemical properties of meconium and influenced anal continence.

[Distribution of fibronectin and laminin during development of the human myenteric plexus and Hirschsprung's disease]. / Distribution de la fibronectine et de la laminine au cours du développement des plexus myentériques humains et dans la maladie de Hirschsprung.

The distribution of fibronectin and laminin, two glycoproteins involved in the migration of neural crest cells, was studied by an indirect immunohistofluorescence technique in 35 embryos and fetuses (from 6 weeks old to birth), 5 normal controls, and 6 patients with Hirschsprung's disease, in order to provide a new approach to the embryogenesis of human myenteric plexus and the pathogenesis of aganglionosis. Fibronectin was not seen near individual neuroblasts unlike myoblasts and mesenchymal cells which were surrounded by this macromolecule. There was a progressive and parallel cephalocaudal development of the plexus and the muscular layers from the esophagus to the intestine. However, in the rectum, at 7 weeks, neuroblasts were detected in close contact to fibronectin-labeled cells whereas they were not in the colon. These present results were in favor of two origins for neuroblasts: the vagal and the caudal neural crest cells. Faulty migration of caudal neural crest cells might be involved in the aganglionosis of Hirschsprung's disease in spite of the fact that local environment of fibronectin and laminin was identical to that of normal subjects.

[Quantification of DNA using image analysis on paraffin sections]. / Quantification de l'ADN par analyse d'image sur coupes en paraffine.

With the new softwares that are available, it is now possible to measure the cellular DNA content on Feulgen stained paraffin sections, without enzymatic dissociation of the samples. The main advantage of this technique is to preserve the cellular histological context and to select the right cells that have to be analyzed. The application is of course to obtain information about cancer prognosis, but it can also be very useful in non tumoral pathology. The DNA measurement on paraffin sections can be applied to the diagnosis of triploidy or tetraploïdy in spontaneous abortions without any karyotype.

[Detection of papillomaviruses by in situ hybridization with sulfonated probes]. / Détection par hybridation in situ des papillomavirus avec des sondes marquées par sulfonation.

A technique of detection by in situ hybridization of human papillomavirus in sections of condylomatous lesions is described. The probes are labeled and modified by sulfonation and the hybrids are revealed by immunohistochemistry, using alkaline phosphatase.

[DNA quantification and triploidy phenotype in the second and third trimesters of pregnancy]. / Quantification de l'A.D.N. et phénotype de triploïdie aux deuxième et troisième trimestres de grossesse.

Triploidy is often associated with early abortions, but may evolve during the second trimester taking a peculiar phenotype. The conditions of diagnosis or abortion do not always let the possibility of karyotyping. Thus, DNA quantification takes all its value. Twenty-three fetuses and placentas, ranging from 14 to 30 weeks of gestation with a phenotype of triploidy were analysed. Twelve cases were proved by karyotype. The DNA index studied in 6 of these was near 1.5, which confirmed the validity of the technique. Out of 11 phenotypes without karyotyping, DNA analysis identified 4 triploidies and a possible tetraploidy. So, a series of 16 cases could be collected, including 10 partial hydatidiform moles and 6 hypotrophic or normal fetuses and placentas.