[Evaluation of rule out strategy for patients with non-ST-elevation acute coronary syndrome with single measurement of high-sensitivity cardiac troponin I from one sample tested beetween 3 and 6 hours after chest pain onset]. / Évaluation d'une stratégie d'exclusion d'un syndrome coronarien aigu non ST+ basé sur une unique mesure de troponine de haute sensibilité à partir d'un prélèvement effectué entre 3 et 6 heures après le début de la douleur.

BACKGROUND: Guidelines recommend to consider excluding non-ST-segment elevation myocardial infarction (NSTEMI) when high-sensitivity cardiac troponin is below the limit of quantification and a single blood sample is taken > 6 h after the onset of chest pain. The aim of our study was to assess such exclusion when a single blood sample was taken 3-6 h after the onset of permanent chest pain. METHODS: This observational study included consecutive patients admitted into the emergency room of our hospital with chest pain and suspected NSTEMI, with non-contributive electrocardiograms and a single high-sensitivity cardiac troponin I (hs-cTnI) blood sample taken 3-6 h after the onset of chest pain and hs-cTnI < 4 ng/l (Abbott Diagnostic). Clinical follow-up was undertaken 1 month after admission. RESULTS: The mean age of the 432 patients was 48.5 ± 5.6 years and 51% were male. Based on a clinical algorithm, the pre-test probability of NSTEMI was low in 70%, and intermediate in 21% of patients. Among 419 patients with available 1-month follow-up data, there were no myocardial infarctions or deaths. Thirty-eight patients (9%) were admitted into hospital but none for cardiac reasons. CONCLUSIONS: Our results suggest that exclusion of NSTEMI in patients with a non-contributive electrocardiogram and a single "negative" troponin test in a blood sample taken 3-6 h after the onset of symptoms is valid.

Ultrasonographic anatomy of the long thoracic nerve: A reappraisal using high frequency (24-MHz) probe.

PURPOSE: The purpose of this study was to analyze the potential of ultrasound with a high frequency probe (24-MHz) in the assessment of the long thoracic nerve (LTN) and describe ultrasonographic landmarks that can be used for standardization. MATERIAL AND METHODS: Ultrasonography analysis of the LTN was done on 2 LTNs in a cadaver specimen and then on 30 LTNs in 15 healthy volunteers (12 men, 3 women; mean age, 28.8±3.8 [SD] years; age range: 24-39 years) by two independent radiologists (R1 and R2) using a 24-MHz probe. Interrater agreement was assessed using Kappa test (K) and intraclass correlation coefficient (ICC). RESULTS: In the cadaver, dissection confirmed that the India ink was injected near the LTN in the middle scalene muscle. In volunteers, visibility of the LTN above the clavicle was highly reproducible for the branches arising from C5 (R1: 87% [26/30]; R2: 90% [27/30]; K=0.83) and from C6 (R1: 100% [30/30]; R2: 97% [29/30]; K=0.94). Where the nerve emerged from the middle scalene muscle, the mean diameter was 0.85±0.24 (SD) mm (range: 0.4-1.6mm) for R1 and 0.9±0.23 (SD) mm (range: 0.4-1.7mm) for R2 (ICC: 0.96; 95% CI: 0.92-0.98%). Along the thoracic wall, where LTN run along the lateral thoracic artery, the mean diameter was 0.83±0.19 (SD) mm (range: 0.5-1.27mm) for R1 and 0.89±0.21 (SD) mm (range: 0.6-1.2mm) for R2 (ICC: 0.86; 95% CI: 0.72-0.93%). CONCLUSION: The LTN can be analyzed with ultrasound using high-frequency probe by using the C5 and C6 roots, the middle scalene muscle above the clavicle and the lateral thoracic artery on the chest wall as landmarks.

Quality of acute heart failure treatment in France: Data from REseau Nord-Alpin des Urgences (RENAU).

BACKGROUND: Although mortality due to acute heart failure has decreased, its prevalence in France is still high. The aim of this study was to examine the quality of acute heart failure treatment in French emergency departments (EDs) with reference to subsequently published European Society of Cardiology (ESC) recommendations. METHODS: The medical records of patients with acute pulmonary oedema (as a marker for acute heart failure) admitted to the EDs of 11 French hospitals in 2013 were reviewed retrospectively. RESULTS: A total of 834 patients were included (median [interquartile range] age 84 [78-89] years; 48.6% male). Rates of compliance of initial management in 2013 to subsequently published 2015 recommendations were as follows: (1) thoracic ultrasound was performed in 17.3%; (2) loop diuretics were given in 75.9%; at a correct dose (among those for whom this was calculable) in 40.0% (3); intravenous nitrates were given in 21.7% of patients with systolic blood pressure>110mmHg; (4) non-invasive ventilation was initiated in 22.0% of patients with respiratory distress. Discharge summaries most often lacked a scheduled cardiologist follow-up (89.4%) and discharge patient weight (78.9%). CONCLUSIONS: The early management of patients with acute pulmonary oedema (as a marker of acute heart failure) in France in 2013 was quite different to recommendations published in 2015. A programme to implement the new recommendations is in place, and a repeat evaluation will be conducted in 2017.

[Evaluation of the incidence of radiodermatitis lesions in interventional cardiology]. / Évaluation de l'incidence des lésions de radiodermite en cardiologie interventionnelle.

PURPOSE: The percutaneous coronary interventions use large doses of ionizing radiation, particularly when treating complex lesions. The incidence of radio-induced skin lesions is poorly known. Our goal was to evaluate the frequency of occurrence of such lesions, as well as the factors that may contribute to a high radiation dose. The recommended DAP (dose-area product) cutoff for skin monitoring after percutaneous coronary interventions is 500Gy cm2. PATIENTS AND METHOD: We prospectively studied the incidence of acute (after 5-7 days) and subacute (after 7 days to 6 months) skin lesions following angioplasty with a dose-area product (DAP) ≥200Gy cm2 in patients who underwent coronary angioplasty in our center in 2013. RESULTS: Nine hundred and thirty three consecutive procedures were analyzed, of which 102 with a DAP ≥200Gy cm2. Three patients presented an acute lesion. Two of these three patients also had subacute lesions. Another patient presented only a subacute lesion. 4.82% (95% CI: [0-10]) of the patients with a DAP ≥200Gy cm2 developed radiodermitis lesions, or 0.47% (95% CI: [0-0.9]) of all the patients who underwent angioplasty. The Body Mass Index and the elective (as opposed to energy) procedures were independently associated with a procedure with a DAP ≥200Gy cm2. CONCLUSION: Radiodermatitis lesions occur for 4.82% of patients benefiting from procedures with a DAP ≥200Gy cm2. We suggest the establishment of a DAP threshold for dermal monitoring of patients of 200Gy cm2 per procedure instead of 500Gy cm2.

Treatment of acute cardiac failure in the emergency department. Improve our practices? Data from the RESURCOR network.

BACKGROUND: In 2015, the European Society of cardiology published guidelines on the pre-hospital and early hospital management of acute cardiac failure (ACF), which included: - use of intravenous vasodilators (nitrates) when systolic blood pressure is>110mmHg; - non-invasive ventilation if oxygen saturation is<90% and/or respiratory rate is>25/min despite nasal oxygen; - using a reduced dose of intravenous furosemide (20-40mg or equivalent of the oral morning dose if already on chronic diuretic therapy) and; - early performance of echocardiography. We sought to compare the gap between these recommendations and clinical practices in French emergency departments (EDs). METHODS: We undertook a retrospective evaluation of clinical practices in 834 consecutive patients with ACF admitted in 2013 to the EDs of 16 French hospitals. Data, including patient characteristics and practices were collected from the medical records. RESULTS: Patients' mean±standard deviation age was 82±10 years and 49% were men. Clinical practices in relation to the guideline recommendations are shown in the Table 1. CONCLUSIONS: These initial data which precede publication of the current guidelines, show that use of nitrates, non-invasive ventilation, reduced diuretic dose and early echocardiography were relatively infrequent at the first point of medical care for patients presenting with ACF. These findings indicate the need for a sizable shift in practice in order to meet the new guideline recommendations. We will conduct a repeat evaluation in 2016, after implementation of a programme aimed to improve practices at these sites.

[Salmonella meningitis in an infant due to a pet turtle]. / Méningite à Salmonelle chez un nourrisson due à une tortue domestique.

In humans, Salmonella most often causes self-limiting gastroenteritis, but more severe symptoms such as sepsis and meningitis can also occur and can sometimes have a fatal outcome. Even if the meningitis is not fatal, sequelae such as epilepsy, cranial nerve palsies, and hydrocephalus can occur. In the United States, it has been estimated that approximately 6% of the human cases of salmonellosis can be attributed to contact with reptiles or amphibians. The infection may take place by direct contact between reptile and human or indirectly via contact with an environment contaminated with Salmonella from a reptile. Salmonella enterica subsp. enterica serotype Vitkin is a common gut inhabitant of reptiles. Though human cases due to this organism are exceedingly rare, it may infect young infants and immunocompromised individuals with a history of intimate associations with reptiles. Gastroenteritis is the most common presentation ; others include peritonitis, meningitis and bacteremia. We report a case of meningitis caused by S. enterica subsp. enterica serotype Vitkin in a 1-month-old child due to a pet turtle.

[Reperfusion in ST elevation myocardial infarction. From the guidelines to practice]. / Reperfusion des infarctus aigus avec sus-décalage du segment ST dans le RENAU/RESURCOR : des recommandations à la pratique.

BACKGROUND: International guidelines have recommendations for selecting the type of reperfusion (fibrinolysis or angioplasty) in the setting of ST-segment elevation myocardial infarction (STEMI), and suggest that emergency-care networks adapt these recommendations according to the local environment. AIM: To assess the proportions of STEMI patients treated with fibrinolysis or angioplasty in accordance with regional guidelines. METHOD: Observational study based on a permanent registry of patients with STEMI of <12h duration in an emergency network in the French North Alps (Isère, Savoie, Haute-Savoie) from January 2009 to December 2012. RESULTS: The registry included 2620 patients. Reperfusion was given in 2425/2620 (93%) of patients. Reperfusion type was in accordance with recommendations in 1567/2620 (60%) patients. Guideline-recommended fibrinolysis and angioplasty were performed in 47% (656/1385) and 79% (911/1149) respectively, of patients. In multivariable analysis, variables independently associated with guideline-recommended reperfusion were: an age < 65 years (OR 1.60; 95%CI 1.33-1.90), being managed in Haute-Savoie versus Isère or Savoie (OR 1.38; 95%CI 1.12-1.71), an arterial tension < 100mmHg (OR 1.73; 95%CI 1.27-2.35), a cardiogenic shock (OR 0.50; 95%CI 0.30-0.84), a pacemaker or left bundle branch block (OR 0.49; 95%CI 0.28-0.88), and an initial management outside the network (followed by treatment in an interventional centre in the network) (OR 0.62; 95%CI 0.40-0.94). Patients initially treated by mobile intensive care units were more often reperfused in accordance with recommendations when admitted < 3 (versus ≥ 3) h following symptom onset (adjusted OR 2.05; 95% CI 1.61-2.59), while those initially treated by in-hospital emergency units were less often reperfused in accordance with recommendation when treated < 3h following symptom onset (adjusted OR 0.67; 95% CI 0.46-0.97). In-hospital major adverse cardiac events (9.1% vs. 8.5%) and in-hospital mortality (6.4% vs. 5.1%) were not significantly different between patients reperfused in accordance with (versus not) recommendations. CONCLUSIONS: Forty percent of patients with STEMI were not reperfused with fibrinolysis or angioplasty in accordance with regional guidelines. Characterization of this population should allow us to improve guideline adherence.

[Management of neuropathic pain in children: guidelines for good clinical practice]. / Prise en charge des douleurs neuropathiques chez l'enfant: recommandations de bonne pratique clinique.

Neuropathic pain exists in children and its incidence is often underestimated due to the lack of knowledge on the existence and the diagnosis of this pain. Although the semiological characteristics can be compared to those of the adult (allodynia, hypoesthesia, burning and stabbing sensations), their etiology often differs, and pain treatments are more limited because of a lack of pharmacological data and the absence of clinical studies. Therapeutic management is sometimes insufficient and requires better knowledge of this entity. Based on the June 2009 recommendations of the French Agency for Food and Drug Safety (Afssaps) (drug therapy in acute and chronic pain in children), this article presents a review of the data available in the literature on the subject, taking into account expert opinion and proposing clinical recommendations of good practice for the recognition and the treatment of neuropathic pain in children.

[Sedation using ketamine for pain procedures in Pediatric Oncology.]. / Sédation par kétamine en prévention de la douleur liée aux gestes invasifs en oncologie pédiatrique.

Procedural sedation and analgesia for children is widely practiced. Since 2005 to 2007, we evaluated the safety and efficacy of ketamine to control pain induced by diagnostic procedures in pediatric oncology patients. Eight hundred fifty procedures were carried out in 125 patients aged 2 to 16 years. We associated EMNO (inhaled equimolar mixture of nitrous oxide and oxygen), atropin (oral or rectal), midazolam (oral or rectal) and ketamin (intravenous). An anesthesiologist injected ketamin. Average dose of ketamine was 0.33 to 2 mg/kg depending on number and invasiveness of procedures. This method requires careful monitoring and proper precautions. With these conditions, no complication was observed. All patients were effectively sedated. These results indicate that ketamine - in association with EMNO, atropine and midazolam - is safe and effective in pain management induced by diagnostic procedures in pediatric oncology patients. The sedative regimen of intravenous ketamine has greatly reduced patient, family and practitioners anxiety for diagnostic and therapeutic procedures.

Cell imaging by coherent backscattering microscopy using frequency-shifted optical feedback in a microchip laser.

In this work, we present a new development of the laser optical feedback imaging technique for imaging biological structures with a high resolution. The first results obtained on human red blood cells and mice cerebral and muscular tissues slices are shown. The performances of the system and its future developments are also discussed.

A one-day survey of characteristics of off-label hospital prescription of psychotropic drugs.

INTRODUCTION: The aim of this study was to explore the characteristics of off-label prescriptions of psychotropic drugs among patients hospitalised in psychiatry. METHODS: A one-day cross-sectional study was used to explore off-label prescribing in patients hospitalised in four wards of a state psychiatric hospital. Information regarding patients and treatment characteristics was collected from medical records. Off-label prescribing was defined according to the Summary of Product Characteristics. RESULTS: Seventy-five patients were included. Of the 261 prescriptions, more than one out of three (n=104, 39.8%) were off-label. Off-label prescribing was particularly high for anticonvulsants (97%), and to a lesser extent for mood stabilisers (33%) and anxiolytics (31%). The rate of off-label prescription was higher for 2nd compared to 1st generation antipsychotics. Most patients (84%) were prescribed at least one psychotropic drug outside of the licensed indication or recommended dosage. Patients with and without off-label prescription did not differ regarding history of prior admission, type of current admission (voluntary vs. compulsory) and diagnosis. CONCLUSION: In spite of its frequency in routine practice, off-label prescribing should not be trivialised. Prescribers should be better informed about the potential legal consequences of off-label prescribing.

[Epidemiology of accidental falls from heights among children, Paris Region, May to September 2005]. / Epidémiologie des chutes accidentelles de grande hauteur chez les enfants en île-de-France entre mai et septembre 2005.

SUMMARY: A survey conducted between May and September 2005 in the Paris Region collected 67 cases of accidental "falls from heights" among the children under the age of 15. Most of the injured children were under the age of 6 (72%), the majority were boys (72%). More than half of the children's families were from extra-European origin, mostly from Sub-Saharan Africa. In 32% of the cases, the fall occurred as the opening had a protection. A piece of furniture was in place beneath the window or was disposed by the child in 55% of the cases; 33% of the children climbed the parapet or the opening. In third of the falls, there was an adult present with the child in the room. Seven children died (10%) and eight (12%) had sequelae. The risk of fall due to the lack of surveillance is not enough known by adults. It is therefore recommended to organise prevention campaigns. To prevent falls, one should revise the regulations for building the parapet and the mechanisms for opening the windows.

Genetic diversity of KIR natural killer cell markers in populations from France, Guadeloupe, Finland, Senegal and Réunion.

Killer cell immunoglobulin-like receptors (KIRs) belong to a diverse family of natural killer (NK) cell receptors recognizing human leukocyte antigen (HLA) class I molecules. Due to this functional link, KIR molecules are expected to display a high polymorphism, such as their HLA ligands. Moreover, many studies conducted in mouse and human models have shown that NK-KIR receptors play an important role in haematopoietic stem cell transplantation (HSCT). A beneficial impact of peculiar KIR ligand (HLA) mismatching has been reported suggesting a role to this combinatory HLA-KIR polymorphism. It is thus important to investigate KIR diversity in various human populations. To this end, we used polymerase chain reaction-sequence-specific primers to evaluate KIR gene in five selected populations (France, Guadeloupe, Senegal, Finland and Réunion). Genotypic and haplotypic frequencies were computed, as well as genetic distances and dendrogram (phylip package). These data illustrate the genetic relationship of these five populations through the KIR polymorphism. Results revealed a wide diversity in KIR gene frequencies in Guadeloupe and Réunion, and a high specificity in Senegal. The obtained dendrogram indicated small genetic distances between France, Guadeloupe and Réunion as well as between France and Finland. Senegal showed a distant genetic relationship with the other countries and, interestingly, an inverted ratio of coding/non-coding (KIR2DS4/1D) alleles compared with Caucasians. These data expose the broad diversity in KIR genes worldwide and show that KIR genes are pertinent tools in human population genetics. If the role of KIR donor-recipient incompatibilities is confirmed, KIR diversity according to ethnicity should be taken into account during the selection of HSCT donors.

Tolerance and analgesic efficacy of a new i.v. paracetamol solution in children after inguinal hernia repair.

BACKGROUND: A new intravenous (i.v.) formulation of paracetamol and propacetamol (prodrug of paracetamol) were compared to determine tolerance and relative analgesic efficacy during the first 6 h after inguinal hernia repair performed under general anesthesia combined with ilioinguinal block in children. METHODS: A total of 183 ASA I or II in-patients, aged 1-12 years, admitted for unilateral inguinal hernia repair were randomized to receive in a double-blind design either i.v. paracetamol 15 mg.kg(-1) (n = 95) or propacetamol 30 mg.kg(-1) (n = 88) for postoperative pain relief as soon as pain intensity was greater than 30 on a 100 mm visual analog scale. All patients were evaluated for efficacy and tolerance. Efficacy was evaluated between 15 min and 6 h after the start of the 15 min infusion. RESULTS: The most frequently reported adverse event was injection site pain, which was significantly reduced in the new formulation group (i.v. paracetamol 14.7% vs propacetamol 33.0% of children, P = 0.005). No significant difference was obtained between treatments on pain relief (PR), pain intensity difference (PAID) from baseline, and objective pain scale intensity difference (OPSD). Also, treatment effects did not differ significantly for maximum values and weighted sums of PR, PAID (investigator and child rated), OPSD, time to first request for rescue medication, proportion of children requesting rescue medication, and investigators' global treatment satisfaction. CONCLUSION: A single infusion of i.v. paracetamol 15 mg.kg(-1) produced analgesia similar to a single infusion of propacetamol 30 mg.kg(-1) following inguinal hernia repair in children. Paracetamol i.v. 15 mg.kg(-1) was better tolerated at the injection site than propacetamol.

[A case of Parkinsonian syndrome, cognitive impairment and hyperammonemia induced by divalproate sodium prescribed for bipolar disorder]. / Troubles cognitifs, syndrome extrapyramidal et hyperammoniémie sous traitement thymorégulateur par divalproate de sodium: a propos d'un cas.

Several cases of Parkinsonian syndrome, cognitive impairment or hyperammonemia induced by sodium valproate have been described in the literature. We report the first case presenting an association of the three adverse effects occurring with divalproate sodium prescribed for bipolar disorder: a 58-year-old man with a history of bipolar type I disorder presented with Parkinsonian syndrome and cognitive impairment of insidious onset. This patient had been treated for several years with lithium carbonate, with a successful effect on mood swings, but with distressing adverse effects such as hand tremor and diarrhoea. Lithium therapy was progressively withdrawn while sodium divalproate was initiated. Associated medications, unchanged for several years, were amisulpride (daily dose: 100 mg), liothyronine, ciprofibrate and benfluorex. The patient was treated with sodium divalproate for seven months (daily dose: 1,000 mg), and with trihexyphenidyle for one month for extrapyramidal symptoms. At hospital admission, he presented with temporal disorientation, slowed thinking, severe anterograde memory deficits, and Parkinsonian syndrome. The minimal mental state (MMS) score was 16 (maximum: 30). The patient was anxious but did no present with mood symptoms. He also developed hyperammonemia (124 micromol/liter, normal range: 15 to 60 micromol/liter) without signs or biochemical evidence of hepatic failure. Valproate concentrations were within the therapeutic ranges (79 mg/l, normal range: 50 to 100 mg/l). The CT-scan showed cerebral and cerebellar atrophy with enlarged ventricles. The electroencephalogram showed generalized slowing waves. All the symptoms resolved within one month after the withdrawal of divalproate: the extrapyramidal hypertonia resolved, the MMS score was 29. The CT-scan and the electroencephalogram returned to normal. The divalproate was replaced by lithium. After a one-year follow-up, the cognitive and neurological symptomatology did not reappear at the exception of the pre-existing hand tremor. The pathophysiology of valproate induced hyperammonemic encephalopathy remains unclear. A possible mechanism is neuronal toxicity induced by increased intracellular concentrations of glutamate and ammonium in astrocytes. Indeed, these abnormal intracellular concentrations increase the intracellular osmolarity and thus induce rise in intracranial pressure and cerebral oedema. Reversible dementia could be due to a direct toxic effect of valproate on the central nervous system or to an indirect effect mediated through valproate-induced hyperammonemia. It has been suggested that the occurrence of extrapyramidal syndrome could be explained by a disturbance in the GABAergic pathways inducing reversible dopamine inhibition. A drug adverse reaction should always be considered when a patient treated with valproate presents with extrapyramidal symptoms and cognitive disorders even when valproate concentrations are within standard therapeutic ranges.

Expression of small heat shock proteins and intermediate filaments in the human optic nerve head astrocytes exposed to elevated hydrostatic pressure in vitro.

The small heat shock proteins (sHSP), alpha B-crystallin and Hsp27 are chaperone molecules that maintain the integrity of intermediate filament (IF) network and prevent unfolding of cellular proteins induced by stress. In the optic nerve head (ONH) of eyes with glaucoma, reactive astrocytes expressed Hsp27, perhaps in response to stress related to elevated intraocular pressure. In this study, we determined the effect of elevated hydrostatic pressure (HP) in the synthesis, distribution and co-localization of alpha B-crystallin and Hsp27 with IF in cultured ONH astrocytes. Astrocyte monolayers were pressurized to 60 mm Hg (92% air 8% CO(2)) and incubated at 37 degrees C for 6, 24 or 48 hr. Controls were exposed to ambient pressure. Cells were analyzed by immunocytochemistry, Western blot and immunoprecipitation using antibodies to Hsp27, alpha B-crystallin, vimentin or GFAP. Control astrocytes seemed flat, polygonal with short processes. alpha B-crystallin appeared granular in the perinuclear area and filamentous in the cell periphery. Fine granular Hsp27 was distributed throughout the cytoplasm. GFAP and vimentin co-localized with Hsp27 in the cytoplasm. Astrocytes exposed to HP were star-shaped with long processes. Hsp27 was condensed in large granules around the nucleus. GFAP and vimentin co-localized with Hsp27 and alpha B-crystallin in the perinuclear area. Western blot and metabolic labeling detected increased synthesis of Hsp27, GFAP and vimentin but no change in alpha B-crystallin. These results indicated that GFAP and vimentin associate with Hsp27 and alpha B-crystallin in ONH astrocytes. HP affected the integrity of the cytoskeleton consistent with morphological changes. Small HSP may reinforce and maintain IF integrity in response to HP.

Drosophila rab GDI mutants disrupt development but have normal Rab membrane extraction.

Rab GTPases are essential for vesicular transport. Rab GDP dissociation inhibitor (GDI) binds to GDP-bound rabs, removes rabs from acceptor membranes and delivers rabs to donor membranes. We isolated lethal GDI mutations in Drosophila and analyzed their developmental phenotypes. To learn how these mutations affect GDI structure, the crystal structure of Drosophila GDI was determined by molecular replacement to a resolution of 3.0 A. Two hypomorphic, missense mutations are located in domain II of GDI at highly conserved positions, but not in previously identified sequence conserved regions. The mutant GDIs were tested for ability to extract rabs from membranes and showed wild-type levels of rab membrane extraction. The two missense alleles showed intragenic complementation, indicating that domain II of GDI may have two separable functions. This study indicates that GDI function is essential for development of a complex, multicellular organism and that puparium formation and pole cell formation are especially dependent on GDI function.

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human optic nerve head astrocytes.

Glaucomatous optic neuropathy is a common blinding disease characterized by remodeling of the extracellular matrix (ECM) and loss of retinal ganglion cell (RGC) axons at the level of the optic nerve head (ONH). Astrocytes, the major cell type in ONH, may participate in this process by production of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). In normal and glaucomatous ONH, we detected MMP and TIMP expression by immunohistochemistry. Cultured astrocytes were used to characterize expression of MMPs and TIMPs by zymography, Western blot, and RNase protection assay. MMP production was stimulated with phorbol 12-myristate 13-acetate (PMA). Astrocytes expressed MMP1, MT1-MMP, MMP2, TIMP1, and TIMP2 in normal and glaucomatous ONH. MMP2, TIMP1, and TIMP2 localized to RGCs and their axons. Increased MMP1 and MT1-MMP expression was demonstrated in glaucoma. Cultured astrocytes constitutively expressed MMP2, MT1-MMP, TIMP1, and TIMP2, whereas MMP3, MMP7, MMP9, and MMP12 were not detectable in tissues or in cultured astrocytes. Our findings demonstrate the presence of specific MMPs and TIMPs in the ONH that may participate in the homeostasis and remodeling of the ECM in glaucoma. Expression of the same MMPs and TIMPs in cultured ONH astrocytes will allow further studies on the mechanisms regulating these enzymes.

Reviews of evidence regarding interventions to reduce tobacco use and exposure to environmental tobacco smoke.

This report presents the results of systematic reviews of effectiveness, applicability, other effects, economic evaluations, and barriers to use of selected population-based interventions intended to reduce tobacco use and exposure to environmental tobacco smoke. The related systematic reviews are linked by a common conceptual approach. These reviews form the basis of recommendations by the Task Force on Community Preventive Services (TFCPS) regarding the use of these selected interventions. The TFCPS recommendations are presented on page 67 of this supplement.