Vigilance in industry: cosmetics and household cleaning products. Balance sheet of case report from 2005 to 2007.

BACKGROUND: Unlike medicinal products, cosmetics are not subject to marketing authorization in France. Nevertheless, the Agence Francaise de Sécurité Sanitaire des Produits de Santé (AFSSAPS; French Agency for the Safety of Healthcare Products) has been working on the development of a cosmetovigilance system for several years, with the aim of establishing standard procedures for collecting adverse reactions to cosmetics from the manufacturers. AIM: To assess the incidence of skin reactions to cosmetics or household products. Unilever established its own 'vigilance' standard system in France in late 2003. This report describes the experience acquired from 2005 to 2007. METHODS: Case reports were collected in compliance with a standard procedure. The cases were then analysed by the consultant dermatologist in accordance with a pharmacovigilance-based method (chronological criteria, clinical criteria, possible rechallenge test, patch tests). RESULTS: During the period 2005 to 2007, a total of 102,689 consumers contacted the consumer department, including 842 (0.82%) who reported skin reactions. After analysis of the collected data, 0.144 skin reaction cases per million units sold were found to be attributable to cosmetic or household products. CONCLUSIONS: The implementation of a structured vigilance system in the cosmetics and household products industry is an efficient tool for manufacturers, both for information purposes and for product improvement, as well as meeting the transparency requirements of health authorities and consumers.

A new agarose-based microsystem to investigate cell response to prolonged confinement.

Emerging evidence suggests the importance of mechanical stimuli in normal and pathological situations for the control of many critical cellular functions. While the effect of matrix stiffness has been and is still extensively studied, few studies have focused on the role of mechanical stresses. The main limitation of such analyses is the lack of standard in vitro assays enabling extended mechanical stimulation compatible with dynamic biological and biophysical cell characterization. We have developed an agarose-based microsystem, the soft cell confiner, which enables the precise control of confinement for single or mixed cell populations. The rigidity of the confiner matches physiological conditions and its porosity enables passive medium renewal. It is compatible with time-lapse microscopy, in situ immunostaining, and standard molecular analyses, and can be used with both adherent and non-adherent cell lines. Cell proliferation of various cell lines (hematopoietic cells, MCF10A epithelial breast cells and HS27A stromal cells) was followed for several days up to confluence using video-microscopy and further documented by Western blot and immunostaining. Interestingly, even though the nuclear projected area was much larger upon confinement, with many highly deformed nuclei (non-circular shape), cell viability, assessed by live and dead cell staining, was unaffected for up to 8 days in the confiner. However, there was a decrease in cell proliferation upon confinement for all cell lines tested. The soft cell confiner is thus a valuable tool to decipher the effects of long-term confinement and deformation on the biology of cell populations. This tool will be instrumental in deciphering the impact of nuclear and cytoskeletal mechanosensitivity in normal and pathological conditions involving highly confined situations, such as those reported upon aging with fibrosis or during cancer.

Successful transcatheter pulmonary valve implantation in a dog: first clinical report.

Transcatheter pulmonary valve (TPV) implantation is a therapeutic approach approved by the United States Food and Drug Administration for human patients with failing pulmonary conduits in 2010 and for failing bioprosthetic surgical pulmonary valves in 2017. We report here the first successful transcatheter implantation of a stented valve in a pulmonary position in a dog with congenital pulmonary valve disease. A 3-year-old, 10.9 kg, client-owned Beagle dog was referred for a follow-up visit after a percutaneous balloon valvuloplasty performed 22 months before for treatment of a severe type A valvular pulmonary stenosis. The Doppler-derived peak pressure gradient was 348 mmHg before the procedure and 66 mmHg 24 h after. The dog was lethargic. Echocardiography revealed a mild pulmonary stenosis (pressure gradient-43 mmHg), severe pulmonary regurgitation, and secondary severe right ventricular and right atrial dilation. Worsening of right heart dilation was observed 2 months later despite medical therapy. A TPV implantation was performed using a prestented Melody bovine jugular bioprosthetic valve. The dog recovered uneventfully and was discharged 10 days after the procedure. Right heart dilation resolved within 15 days. The dog was doing well 7 months after valve implantation. This case demonstrates that TPV implantation with a stented valve is technically feasible in dogs with severe pulmonary valve disease. Stringent postoperative care, with particular attention to thrombosis and infectious endocarditis, and appropriate sizing and positioning of the valve stent are keys to the success of this procedure.

CXCR4 inhibitors could benefit to HER2 but not to triple-negative breast cancer patients.

The CXCR4 receptor and its ligand CXCL12 (also named stromal cell-derived factor 1, SDF1) have a critical role in chemotaxis and homing, key steps in cancer metastasis. Although myofibroblasts expressing CXCL12 are associated with the presence of axillary metastases in HER2 breast cancers (BC), the therapeutic interest of targeting CXCR4/CXCL12 axis in the different BC subtypes remains unclear. Here, we investigate this question by testing antitumor activity of CXCR4 inhibitors in patient-derived xenografts (PDX), which faithfully reproduce human tumor properties. We observed that two CXCR4 inhibitors, AMD3100 and TN14003, efficiently impair tumor growth and metastasis dissemination in both Herceptin-sensitive and Herceptin-resistant HER2 BC. Conversely, blocking CXCR4/CXCL12 pathway in triple-negative (TN) BC does not reduce tumor growth, and can even increase metastatic spread. Moreover, although CXCR4 inhibitors significantly reduce myofibroblast content in all BC subtypes, they decrease angiogenesis only in HER2 BC. Thus, our findings suggest that targeting CXCR4 could provide some therapeutic interest for HER2 BC patients, whereas it has no impact or could even be detrimental for TN BC patients.

IL-13 and IL-4 share signal transduction elements as well as receptor components in TF-1 cells.

IL-13 and IL-4 are growth factors for the human erythroleukemia cell line TF-1. In these cells both cytokines share overlapping binding sites, but the number of sites for IL-13 is half of that for IL-4. Two monoclonal antibodies against the extracellular domain of the IL-4R alpha chain completely abolish the binding of IL-13, although IL-13 does not bind to this chain. Following receptor triggering, IL-13 and IL-4 induce the phosphorylation of a 170 kDa protein, probably the IL-4-induced phosphotyrosine substrate. In addition the phosphorylation of the 170 kDa protein results in its tight association with phosphatidylinositol-3-kinase.

Primary structure and functional expression of mouse pituitary and human brain corticotrophin releasing factor receptors.

Corticotrophin-releasing factor (CRF) is the principal hypothalamic factor governing the pituitary-adrenal axis, but the wide extra-pituitary distribution of CRF and its receptors suggest a major role for this neuropeptide in the integration of the overall physiological and behavioral responses of an organism to stress. We have cloned a CRF receptor complementary DNA (cDNA) by expression in COS-7 cells of a cDNA library from the AtT20 mouse pituitary tumour cell line. The cloned mouse cDNA was then as a probe to isolate a human CRF receptor cDNA from a human brain cDNA library. The mouse and human cDNAs both encode 415 amino acid proteins that are 97% identical, containing seven putative transmembrane domains characteristic of G protein-coupled receptors. The CRF receptor shows homology with the receptors for growth hormone-releasing factor, vasoactive intestinal peptide, secretin, parathyroid hormone, and calcitonin. COS-7 cells transfected with the mouse CRF receptor cDNA bind radiolabelled ovine CRF with high affinity and respond specifically to CRF by accumulation of intracellular cAMP. A 2.7 kb mRNA coding for the CRF receptor could be detected in AtT20 cells and human cortex tissue. PCR analysis also detected the receptor transcript in human pituitary, brainstem, and testis.

Cloning and expression of a complementary DNA encoding a high affinity human neurotensin receptor.

A human neurotensin receptor (hNTR) cDNA was cloned from the colonic adenocarcinoma cell line HT29. The cloned cDNA encodes a putative peptide of 418 amino acids with 7 transmembrane domains. The amino acid sequence of the hNTR is 84% identical to the rat NTR [Neuron, 4 (1990) 847-854]. Transfection of this cDNA into COS cells results in the expression of receptors with pharmacological properties similar to those found with HT29 cells. Northern blot analysis using the hNTR cDNA probe indicated a single transcript of 4 kb in the brain, the small intestine and blood mononuclear cells.

Randomized controlled trial of a community-based psychoeducation program for the self-management of chronic pain.

Although chronic pain is a frequent cause of suffering and disability and is costly to society, there continues to be limited access to specialty pain clinic services. Hence, there is a need for cost-effective, accessible interventions that will help people find ways to better manage this difficult problem. This randomized controlled trial examined the effect of a low-cost, community-based, nurse-delivered, group psychoeducation program entitled the Chronic Pain Self-Management Program (CPSMP). It has a standard protocol that was modified from the successful Arthritis Self-Management Program (ASMP). One hundred and ten individuals with mixed idiopathic chronic pain conditions were enrolled in the study (75% female; mean age 40 years; mean chronicity 6 years) and were randomly assigned to one of two conditions: the 12-h (CPSMP) intervention group, or the 3-month wait-list control group. Self-report measures of pain-related and other quality of life variables as well as two hypothesized mediating variables were collected pre-treatment and 3 months later by assessors blind to group allocation. One hundred and two subjects completed the study. Results of intention-to-treat analysis indicated that the treatment group made significant short-term improvements in pain, dependency, vitality, aspects of role functioning, life satisfaction and in self-efficacy and resourcefulness as compared to the wait-list control group. Because it has a standard protocol, this intervention has the potential to be reliably delivered at low cost in varied urban and rural community settings and hence be more widely accessible to a greater number of people suffering from chronic pain than is currently the case with more specialized pain clinic services. Based on the results of this study, further research evaluating the long-term impact and potential cost savings to the individual and to the health care system is warranted.

The biological activities of gro beta and IL-8 on human neutrophils are overlapping but not identical.

Gro beta and IL-8 are two members of the small induced secreted (SIS) cytokine family (C-X-C subgroup) with proinflammatory activities on neutrophils. In order to assess whether or not the interaction with their receptors results in similar biological actions, we compared the two cytokines in five different bioassays. Gro beta showed similar biological activities as IL-8 in tests of chemotaxis, induction of the respiratory burst, and induction of interleukin 6 (IL-6) production. However, for two other biological activities: augmentation of the expression of CD11b on the cell surface and rapid elevation of the intracellular calcium concentration, maximal effects required 100 times more gro beta than IL-8. Taken together, these results suggest that the stimulation of the IL-8 or gro beta receptor evokes three similar responses, but that only the activation of the IL-8 receptor and not that of gro beta results in elevated CD11b expression and calcium mobilization in human neutrophils.

Functional linkage of the Gro beta and IL-8 receptors on the surface of human neutrophils.

Gro beta and IL-8 are two pro-inflammatory cytokines with chemotactic activities on neutrophils. Binding studies were performed to ascertain whether their similar biological activities are mediated through the same receptor. Since Gro beta lacks tyrosine residues, recombinant Gro beta containing an additional carboxyterminal tyrosine residue (Gro beta-Tyr) was produced in transfected COS cells, purified to homogeneity and radiolabelled with 125INa. Saturation experiments using [125I]-Gro beta-Tyr allowed us to identify high affinity receptors on human neutrophils (Kd: 2 +/- 0.5 nM and Bmax: 4760 +/- 761 sites/cell). Experiments using [125I]-IL-8 as ligand, showed no significative differences in affinity (Kd: 4 +/- 0.9 nM) but about two times the number of sites (11316 +/- 1810 sites/cell). In competition experiments using [125I]-Gro beta-Tyr, unlabelled IL-8 and Gro beta-Tyr generated superposable displacement curves (IC50: 0.69 +/- 0.15 nM and 0.42 +/- 0.11 nM, respectively). Interesting, IL-8 binding sites could be down-regulated by Gro beta and IL-8, indicating that the two binding sites may be associated. Cross-linking experiments using [125I]-IL-8 revealed two major bands at 70 and 140 kDa, whereas experiments with [125I]-Gro beta-Tyr showed only the 70 kDa band. Taken together, these results suggest that the human neutrophil IL-8/Gro beta receptor is a dimeric complex with two high affinity binding sites for IL-8 and of those two, only one is shared by Gro beta.

Interleukin-6 regulation of CCK/gastrin receptors and amylase secretion in a rat pancreatic acinar cell line (AR4-2J).

In necrotizing pancreatitis a high interleukin-6 (IL-6) serum level has been proposed as a prognostic criterium. However, literature does not report any information about the role of IL-6 in the function of pancreatic acinar cells. Cholecystokinin, gastrin binding, amylase release and intracellular calcium measurement were performed on a rat pancreatoma cell line, AR4-2J, which has been recognized as a useful tool for studies on the long-term regulation of pancreatic acinar cells. The addition of IL-6 (400 pM) for 48hrs to the AR4-2J cells induced no change in the binding affinities but there was a 2 fold increase in the binding capacity of cholecytokinin (CCKA R) and gastrin (CCKB R) receptors. Although IL-6 treatment did not change directly the secretory capacity and did not activate the intracellular calcium mobilization of AR4-2J, it indirectly increased the sensitivity of the cells to the stimulation of amylase release and the intracellular calcium mobilization by cholecystokinin and gastrin. It is most likely this effect was due to the IL-6-induced increase in the numbers of CCKA R and CCKB R. Therefore this report suggests that the cytokine IL-6 acts on the CCK regulation of pancreatic enzyme secretion.

A case report of Down syndrome and centroblastic lymphoma.

We describe a case of left cervical stage I centroblastic lymphoma in a 29-year old male patient with Down's syndrome due to a (14; 21) Robertsonian translocation. The disease presented as extensive lymph node necrosis leaving rare areas of tumor cells, accounting for the diagnostic difficulties. According to our review of the literature, lymphoma is one of the most common neoplasms in DS patients and may represent the second most common malignancy in this condition, far behind leukemia.

Clinical course of premature infants intubated in the delivery room, submitted or not to porcine-derived lung surfactant therapy within the first hour of life.

OBJECTIVES: The aim of this study was to perform a comparative analysis of the clinical outcome, gasometric course and ventilatory indices of premature infants with a gestational age of < or = 34 weeks who were intubated in the delivery room, owing to respiratory insufficiency, according to whether or not they were submitted to porcine-derived lung surfactant therapy within the first hour of life. METHODS: The study was randomized and controlled. A total of 75 premature infants were classified into two groups: group A, comprising 35 neonates who were submitted to surfactant within the first hour of life; and group B, comprising 40 neonates who were not submitted to surfactant within the first hour of life. RESULTS: Exogenous surfactant therapy after establishment of respiratory distress syndrome (RDS) was necessary in eight neonates of group A (22.9%) and 31 neonates of group B (77.5%) (p < 0.001). The neonates in group A presented higher levels in relation to group B for the variables: partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) and PaO2/partial pressure of alveolar oxygen (PAO2), while neonates in group B presented higher levels for FiO2, PAO2 and difference D(A - a)O2 in relation to group A. Weight affected the oxygenation index (OI) parameter, in that neonates with lower weight presented greater values of the OI. CONCLUSIONS: In premature infants with established RDS, the need for exogenous surfactant was lower in the group that received surfactant within the first hour of life. Furthermore, the gasometric parameters and ventilatory indexes presented a better course in the first 24 h of life among premature infants who received exogenous surfactant within the first hour of life, in relation to those who did not.

[Fibrinolysis of deep venous thrombosis on implantable perfusion devices. Apropos of a consecutive series of 57 cases of thrombosis and 32 cases of fibrinolysis]. / Fibrinolyse des thromboses veineuses profondes sur dispositifs de perfusion implantables. A propos d'une série consécutive de 57 thromboses et de 32 fibrinolyses.

The main complication of totally implantable venous access devices is deep venous thrombosis on catheter. It may dramatically reduce the already limited venous capacity of patients undergoing chemotherapy and obturate catheters, causing pulmonary embolism or functional disorders. These thromboses usually involve veins of the superior vena cava system where the catheters are implanted. Generally, they occur early, are extensive and often asymptomatic. Doppler ultrasonography is the diagnostic investigation of choice, phlebography being reserved for particular cases or to specify the limits of the thrombus. In a series of 412 vein access devices implanted and systematically monitored by Doppler ultrasonography, we found 57 thromboses (13.8%), 15 partial and 42 complete. The lowest thrombosis rate was observed in the right internal jugular vein (10% vs 20 to 23%, p = 0.006). Thirty-two patients received a systemic fibrinolytic treatment, 16 with streptokinase (SK), five with urokinase (UK), four with tissue plasminogen activator (rt-PA) and seven with SK/UK association. No serious side effects were observed. Sixteen repermeabilizations (50% of fibrinolysis) were obtained. There were no significant differences with respect to the fibrinolytic, the initial characteristics of thrombosis or the patients. Patients without fibrinolysis received 3 weeks of low molecular weight heparin (curative doses) then warfarin. Only one patient was repermeabilized with this treatment (significative difference with fibrinolysis: p = 0.009). Fibrinolysis is indicated in symptomatic thrombosis and/or in cases of extension to the innominate vein or the superior vena cava. Systematic monitoring by Doppler ultrasonography and prophylactic anti-thrombotic treatment are recommended in patients with implantable venous access devices in order to decrease the occurrence of thromboses, to detect asymptomatic patients at an early stage and to increase the effectiveness of fibrinolysis.

Herpes zoster and postherpetic neuralgia: the need for early intervention in the elderly.

Herpes zoster is an acute nervous system infection that commonly affects the elderly. Because the causative agent is a virus, herpes zoster is often treated symptomatically in the primary care setting. While this approach is acceptable for immunocompetent patients less than 50 years of age, it can leave older patients at greater risk of developing painful and debilitating complications such as postherpetic neuralgia. There is evidence that appropriate treatment initiated within 48 to 72 hours after the onset of the zoster eruption can decrease healing time, reduce acute pain, decrease ocular complications and may prevent the development of postherpetic neuralgia in this age group. The health care practitioner in a primary care setting is ideally placed to identify elderly clients with herpes zoster in the early stages; to consult with physicians about therapies such as steroids, antiviral agents and sympathetic nerve blocks; to monitor treatment effects; and to provide supportive therapy to those who develop postherpetic neuralgia.

Shaping health care policy.

At home and abroad, the Canadian health care system has long been regarded as one of the best in the world. However, it is facing internal and external pressures to change. There is a perception that the traditional system, with its emphasis on physician services and acute care hospital-based services, is being threatened. So, too, are the five principles--universality, accessibility, portability, comprehensiveness, and public administration--under which the system operates.