Comparing potentially avoidable hospitalization rates related to ambulatory care sensitive conditions in Switzerland: the need to refine the definition of health conditions and to adjust for population health status.

BACKGROUND: Regional rates of hospitalization for ambulatory care sensitive conditions (ACSC) are used to compare the availability and quality of ambulatory care but the risk adjustment for population health status is often minimal. The objectives of the study was to examine the impact of more extensive risk adjustment on regional comparisons and to investigate the relationship between various area-level factors and the properly adjusted rates. METHODS: Our study is an observational study based on routine data of 2 million anonymous insured in 26 Swiss cantons followed over one or two years. A binomial negative regression was modeled with increasingly detailed information on health status (age and gender only, inpatient diagnoses, outpatient conditions inferred from dispensed drugs and frequency of physician visits). Hospitalizations for ACSC were identified from principal diagnoses detecting 19 conditions, with an updated list of ICD-10 diagnostic codes. Co-morbidities and surgical procedures were used as exclusion criteria to improve the specificity of the detection of potentially avoidable hospitalizations. The impact of the adjustment approaches was measured by changes in the standardized ratios calculated with and without other data besides age and gender. RESULTS: 25% of cases identified by inpatient main diagnoses were removed by applying exclusion criteria. Cantonal ACSC hospitalizations rates varied from to 1.4 to 8.9 per 1,000 insured, per year. Morbidity inferred from diagnoses and drugs dramatically increased the predictive performance, the greatest effect found for conditions linked to an ACSC. More visits were associated with fewer PAH although very high users were at greater risk and subjects who had not consulted at negligible risk. By maximizing health status adjustment, two thirds of the cantons changed their adjusted ratio by more than 10 percent. Cantonal variations remained substantial but unexplained by supply or demand. CONCLUSION: Additional adjustment for health status is required when using ACSC to monitor ambulatory care. Drug-inferred morbidities are a promising approach.

Percutaneous biopsy through the foramen ovale for parasellar lesions: surgical anatomy, method, and indications.

Knowledge of the pathological diagnosis before deciding the best strategy for treating parasellar lesions is of prime importance, due to the relative high morbidity and side-effects of open direct approaches to this region, known to be rich in important vasculo-nervous structures. When imaging is not evocative enough to ascertain an accurate pathological diagnosis, a percutaneous biopsy through the transjugal-transoval route (of Hartel) may be performed to guide the therapeutic decision.The chapter is based on the authors' experience in 50 patients who underwent the procedure over the ten past years. There was no mortality and only little (mostly transient) morbidity. Pathological diagnosis accuracy of the method revealed good, with a sensitivity of 0.83 and a specificity of 1.In the chapter the authors first recall the surgical anatomy background from personal laboratory dissections. They then describe the technical procedure, as well as the tissue harvesting method. Finally they define indications together with the decision-making process.Due to the constraint trajectory of the biopsy needle inserted through the Foramen Ovale, accessible lesions are only those located in the Meckel trigeminal Cave, the posterior sector of the cavernous sinus compartment, and the upper part of the petroclival region.The authors advise to perform this percutaneous biopsy method when imaging does not provide sufficient evidence of the pathological nature of the lesion, for therapeutic decision. Goal is to avoid unnecessary open surgery or radiosurgery, also inappropriate chemo-/radio-therapy.

Phytochemical investigation of plants used in African traditional medicine: "Dioscorea sylvatica" (Dioscoreaceae), "Urginea altissima" (Liliaceae), "Jamesbrittenia fodina" and "Jamesbrittenia elegantissima" (Scrophulariaceae)

Les plantes médicinales représentent la seule source de médicaments pour près de 90 % de la population de certains pays d?Afrique. Le savoir-faire des guérisseurs traditionnels, d?une valeur inestimable, représente un point de départ pour l?investigation pharmacologique et phytochimique de ces médicaments naturels. Dans le cadre de ce travail, nous nous sommes dans un premier temps intéressés à valider l?utilisation en médecine traditionnelle de deux plantes, Diuscorea sylvatica (Dioscoreaceae) et Urginea altissima (Liliaceae), qui produisent, lorsqu?elles sont frottées sur la peau, une inflammation et des démangeaisons. Ces réactions cutanées ont pu être expliquées, au moins en partie, par la présence d?aiguilles acérées d?oxalate de calcium dans les organes souterrains. Ces microtraumatismes répétés de l?épiderme risquent de provoquer, lors d?une utilisation prolongée, des lésions granulomateuses. L?histamine n?a pas été détectée, mais d?autres substances pourraient être impliquées dans le processus inflammatoire. La seconde partie de ce travail a consisté en la détection, l?isolement et la caractérisation de nouveaux composés naturels présentant un intérêt thérapeutique potentiel. 70 extraits provenant de 28 plantes supérieures du Zimbabwe ont été soumis à un criblage chimique et biologique. Les extraits méthanoliques des parties aériennes de Jamesbrittenia fodina et J. elegantissima (Scrophulariaceae) ont été sélectionnés sur la base de leurs nombreuses activités. Le fractionnement guidé par l?activité de J. fudina a permis l?isolement des saponines A et B, responsables des activités antifongique, antibactérienne et molluscicide de l?extrait. De plus, les deux saponines ont montré une activité équivalente en tant qu?inhibiteurs de l?acétylcholinestérase, propriété encore non décrite pour cette classe de composés. Une analyse LC/uv/MS de l?extrait a permis d?attribuer l?activité antiradicalaire au verbascoside, un dérivé du phenylpropane; cette analyse a de plus montré la présence d?une série de dérivés de l?acide cinnamique, dont l?isolement a été entrepris. Deux problèmes d?instabilité sont apparus, empêchant l?isolement des composés par des méthodes chromatographiques de pointe, en dépit de très bonnes conditions de séparations. Des analyses LC/?H-NMR combinées à des analyses RMN classiques des mélanges ont permis d?attribuer ces instabilités d?une part à une isomérisation cis/trans induite par la lumière, et d?autre part à une transacylation du groupe cinnamoyl sur une unité de sucre. Ceci a permis l?identification de 12 esters cinnamiques d?iridoïdes, dont 8 nouveaux produits naturels. Ces dérivés présentent un intérêt thérapeutique, car des composés similaires ont montré des propriétés anti-inflammatoires significatives dans différents modèles in vivo. Deux flavanones ont aussi été isolées de l?extrait. Cette classe de composés n?a jamais été rapportée chez un membre des Scrophulariaceae. Une analyse LC/UV/MS comparative des extraits polaires des deux espèces, J. fodina et J. elegantissima, a été effectuée pour détecter la présence éventuelle de compos.és communs. Les saponines A et B et le verbascoside ont été identifiés dans l?extrait de J. elegantissima. Trois flavonoïdes ont de plus été isolés de ce dernier par CPC et HPLC semi-préparative.<br/><br/>In certain African countries, medicinal plants represent the unique source of to 90% of the population. The knowledge of traditional healers represents a basis for the pharmacological and phytochemical investigation of these natural medicines. This work first focused on the validation of use of two plants frequently employed in traditional medicine, Dioscorea sylvatica (Dioscoreaceae) and Urginea altissimu (Liliaceae), which produce mild inflammation and itching when rubbed on the skin. These cutaneous reactions were shown to be due, at least in part, to the presence of sharp needles of calcium oxalate, implying the risk of granulomatous lesions following a long term use. Histamine was not detected, but other compounds could be involved in the inflammatory process. The second part of this work consisted of the detection, isolation and characterisation of new natural compounds of potential therapeutic interest from African plants. Seventy extracts obtained from 28 higher plants of Zimbabwe were submitted to a chemical and biological screening. The methanol extracts of the whole plants of Jamesbrittenia fodina and J. elegantissima (Scrophulariaceae) were selected for their various activities. An activity-guided fractionation of J. fodina led to the isolation of the saponins A and B, responsible for the antifungal, antibacterial and molluscicidal properties. Both saponins were equally active as inhibitors of acetylcholinesterase, a property that has, to our knowledge, never been described for this class of compounds. A LC/UV/MS analysis of the extract allowed the identification of verbascoside as the product with radical scavenging activity, and indicated the presence of a series of potentially interesting cinnamic acid derivatives. Two types of instability problems occurred in the course of their isolation, as some compounds could not be separated despite very good chromatographic conditions. LC/'H-NMR analyses combined with in-mixture NMR analyses enabled the attribution of the cause of the instability in one case to a cidtrans light-induced isomerisation, and in the other case to a transacylation of the cinnamoyl moiety on a sugar residue. These problems of instability have not been the object of previous studies. 12 cinnamic iridoid esters could be characterised, 8 of these being new natural compounds. Several similar substances have displayed significant anti-inflammatory properties in different in vivo models, suggesting a therapeutic interest for these new derivatives. Two flavanones were isolated from the same extract. This class of compound has not been previously reported from species of the Scrophulariaceae family. A comparative LCAJVNS study of the polar extracts of the two species J. elegantissima and J. fodina was performed in order to detect possible common compounds. Saponins A and B and verbascoside were thus identified in .J. elegantissima. Moreover, three supplementary flavonoids were isolated from J. elegantissima..

Functions of the human papillomavirus type 16 E4 protein

1. Abstract Cervical cancer is thought to be the consequence of infection by human papillomaviruses (HPV). In the majority of cases, DNA from HPV type 16 (HPV16) is found in malignant cervical lesions. The initial steps leading to transformation of an infected cell are not clearly understood but in most cases, disruption and integration of the episomal viral DNA must take place. As a consequence, the E2 and E4 genes are usually not expressed whereas the E6 and E7 oncogenes are highly expressed. However, in a normal infection in which the viral DNA is maintained as an episome, all viral genes are expressed. The pattern according to which the viral proteins are made, and therefore the life cycle of the virus, is tightly linked to the differentiation process of the host keratinocyte. The study of the viral oncogenes E6 and E7 has revealed crucial functions in the process of malignant transformation such as degradation of the p53 tumor suppressor protein, deregulation of the Retinoblastoma protein pathway and activation of the telomerase ribonucleoprotein. All these steps are necessary for cancerous lesions to develop. However, the loss of the E2 gene product seems to be necessary for sufficient expression of E6 and E7 in order to achieve such effects. In normal infections, the E4 protein is made abundantly in the later stages of the viral life cycle. Though extensive amounts of work have been carried out to define the function of E4, it still remains unclear. In this study, several approaches have been used to try and determine the functions of E4. First, a cell-penetrating fusion protein was designed and produced in order to circumvent the chronic difficulties of expressing E4 in mammalian cells. Unfortunately, this approach was not successful due to precipitation of the purified fusion protein. Second, the observation that E4 accumulates in cells having modified their adhesion properties led to the hypothesis that E4 might be involved in the differentiation process of keratinocytes. Preliminary results suggest that E4 triggers differentiation. Last, as E4 has been reported to collapse the cytokeratin network of keratinocytes, a direct approach using atomic force microscopy has allowed us to test the potential modification of mechanical properties of cells harboring reorganized cytokeratin networks. If so, a potential role for E4 in viral particle release could be hypothesized. 2. Résumé Il a été établi que le cancer du col de l'utérus se développe essentiellement à la suite d'une infection par le virus du papillome humain (HPV). Dans la majorité des cas analysés, de l'ADN du HPV de type 16 (HPV16) est détecté. Les étapes initiales de la transformation d'une cellule infectée sont mal connues mais il semble qu'une rupture du génome viral, normalement épisomal, suivi d'une intégration dans le génome de la cellule hôte soient des étapes nécessaires dans la plupart des cas. Or il semble qu'il y ait une sélection pour les cas où l'expression des oncogènes viraux E6 et E7 soit favorisée alors que l'expression des gènes E2 et E4 est en général impossible. Par contre, dans une infection dite normale où le génome viral n'est pas rompu, il n'y pas développement de cancer et tous les gènes viraux sont exprimés. L'ordre dans lequel les protéines virales sont produites, et donc le cycle de réplication du virus, est intimement lié au processus de différentiation de la cellule hôte. L'étude des protéines oncogènes E6 et E7 a révélé des fonctions clés dans le processus de transformation des cellules infectées telles que la dégradation du suppresseur de tumeur p53, la dérégulation de la voie de signalisation Rb ainsi que l'activation de la télomérase. Toutes ces activités sont nécessaires au développement de lésions cancéreuses. Toutefois, il semble que l'expression du gène E2 doit être empêchée afin que suffisamment des protéines E6 et E7 soient produites. Lorsque le gène E2 est exprimé, et donc lorsque le génome viral n'est pas rompu, les protéines E6 et E7 n'entraînent pas de telles conséquences. Le gène E4, qui se trouve dans la séquence codante de E2, a aussi besoin d'un génome viral intact pour être exprimé. Dans une infection normale, le gène E4 est exprimé abondamment dans les dernières étapes de la réplication du virus. Bien que de nombreuses études aient été menées afin de déterminer la fonction virale à E4, aucun résultat n'apparaît évident. Dans ce travail, plusieurs approches ont été utilisées afin d'adresser cette question. Premièrement, une protéine de fusion TAT-E4 a été produite et purifiée. Cette protéine, pouvant entrer dans les cellules vivantes par diffusion au travers de la membrane plasmique, aurait permis d'éviter ainsi les problèmes chroniques rencontrés lors de l'expression de E4 dans les cellules mammifères. Malheureusement, cette stratégie n'a pas pu être utilisée à cause de la précipitation de la protéine purifiée. Ensuite, l'observation que E4 s'accumule dans les cellules ayant modifié leurs propriétés d'adhésion a suggéré que E4 pourrait être impliqué dans le procédé de différentiation des kératinocytes. Des résultats préliminaires supportent cette possibilité. Enfin, il a été montré que E4 pouvait induire une réorganisation du réseau des cytokératines. Une approche directe utilisant le microscope à force atomique nous a ainsi permis de tester une potentielle modification des propriétés mécaniques de cellules ayant modifié leur réseau de cytokératines en présence de E4. Si tel est le cas, un rôle dans la libération de particules virales peut être proposé pour E4.

Dysregulated activation of the CXCR4/CXCL12 Axisand its role in the malignant phenotype of neural crest-derived neuroblastoma tumours

Résumé: Le neuroblastome (NB) est un néoplasme dévastateur de la petite enfance, pour lequel il n'existe pas encore de traitement efficace. Les chimiokines et leurs récepteurs ont été impliqués dans la croissance des tumeurs et la formation de métastases, et en particulier, il a été rapporté que l'axe CXCR4/CXCL12 dirigeait le guidage, ainsi que l'invasion des cellules cancéreuses vers des organes spécifiques. Notre étude avait pour objectif d'analyser le rôle de CxCR4 exogène dans le comportement malin du NB, en étudiant la croissance des cellules tumorales, leur capacité de survie, de migration et d'invasion in vitro et en validant ces résultats grâce à un modèle orthotopique murin de la progression tumorale du NB in vivo. La surexpression de CXCR4 dans les cellules faiblement métastatiques IGR-NB8 n'exprimant pas CXCR4, a augmenté la mobilité des cellules vers CXCL12 in vitro. De plus, les cellules surexprimant CXCR4 ont été moins affectées par la privation de sérum que les cellules contrôles. Le volume des tumeurs chez les animaux greffés de manière orthotopique avec les cellules NB8-CXCR4-C3 était significativement plus élevé que celui des tumeurs issues des cellules contrôles NB8-E6 au moment du sacrifice des animaux. Cependant, aucune induction des métastases n'a été observée. La lignée cellulaire IGR-N91, aux propriétés invasives et métastatiques in vivo, exprime constitutivement des quantités modérées de CXCR4. La surexpression du récepteur dans cette lignée a accéléré la croissance tumorale in vivo, mais n'a pas augmenté pas l'occurrence des métastases. Les cellules IGR-N91, dans lesquelles l'expression de CXCR4 a été éteinte, suite à l'introduction de shRNA stable contre CXCR4, a présenté une croissance cellulaire plus lente, in vitro et in vivo. Afin d'identifier les gènes et les voies de signalisation impliqués dans les effets dépendants de CXCR4-CXCL12 dans le NB, des analyses du profil d'expression des gènes ont été effectuées sur les lignées cellulaires transfectées ou non (contrôle). Trois clones contrôles ont été comparés à 3 clones surexprimant CXCR4 pour chacune des lignées (IGR-NB8 et IGR-N91). Les analyses biostatiques ont identifié 10 gènes induits, dont CXCR4, et 31 gènes réprimés, communs entre tous les clones surexprimant CXCR4. Ces observations démontrent que la surexpression de CXCR4 dans le NB stimule la croissance, la survie et la migration chémotactique des cellules tumorales, mais est insuffisante pour induire ou augmenter leurs capacités invasives et métastatiques. Les voies de signalisation activées suite à la surexpression de CXCR4 et identifiées à travers le profil global de l'expression des gènes pourraient être des cibles intéressantes pour le développement de drogues capables d'inhiber la croissance tumorale. Abstact: Neuroblastoma (NB) is a devastating childhood neoplasm for which there is not yet an efficient treatment. Chemokines and their receptors have been involved in tumour growth and metastasis, and in particular the CXCR4/CXCL12 axis has been reported to mediate organ-specific cancer cells homing and invasion. The purpose of the study was to investigate the role of ectopic CXCR4 in the malignant behaviour of NB by studying tumour cell growth, survival, migration, and invasion in vitro and by validating these results using a murine orthotopic model of NB tumour progression in vivo. CXCR4 overexpression in the low metastatic, CXCR4-negative IGR-NB8 cells resulted in CXCL12-mediated chemotaxis in vitro. Furthermore, CXCR4 overexpressing cells were less affected by serum deprivation than mock-transduced cells. In vivo studies revealed that, at sacrifice, volumes of tumours developing in mice with orthotopically implanted NB8-CXCR4-C3 cells, were significantly increased compared to NB8-E6 control tumours. However, no induction of metastases was observed. The in vivo invasive and metastatic cell line IGR-N91 cell line constitutively expresses moderate levels of CXCR4. Overexpression of CXCR4 enhanced in vivo tumour growth but did not increase the occurrence of metastases. IGR-N91 cells where CXCR4 has been knocked-down by stable shRNA grew slower in vitro and in vivo. To identify genes and pathways involved in the CXCR4/CXCL12-mediated effects in NB expression, profiles analyses (Affymetrix) were performed on transduced and control cell lines. Three mock-transduced clones were compared to three CXCR4 overexpressing clones of either cell line IGR-NB8 and IGR-N91. Biostatistical analysis identified 10 commonly upregulated genes (including CXCR4) and 31 downregulated genes common to all CXCR4 overexpressing clones. These observations demonstrate that overexpression of CXCR4 in NB stimulates tumour cell growth, survival, and chemotactic migration but is not sufficient to induce or enhance invasive and metastatic capacities. Activated pathways upon CXCR4 overexpression, identified through global gene expression profiling may be interesting targets for drugs inhibiting tumour growth.

Chiasmatic infiltration secondary to late malignant transformation of retinoma.

PURPOSE: To report the lethal course of malignant transformation of retinoma in an adult. METHODS: Case report. A 40-year-old patient presented with retinoma in his right eye and retinoblastoma in his left eye. Enucleation was recommended but refused and the patient received whole eye radiotherapy elsewhere. Five years later he presented again, with temporal hemianopsia of the left eye secondary to chiasmatic invasion. RESULTS: Diagnosis of retinoblastoma infiltration was confirmed by stereotactic biopsy of the chiasmatic lesion. Treatment with intravenous and intrathecal chemotherapy led to partial remission, and was followed by stereotactic irradiation of the chiasmatic mass and right optic nerve. The left eye was enucleated. Death occurred one year later due to cerebrospinal fluid metastases. CONCLUSION: Extraocular extension of retinoblastoma diagnosed in adulthood has never, to our knowledge, been reported. This case stresses the importance of lifelong retinoma monitoring and the necessity for radical treatment in the event of malignant transformation.

Multifunctional mitoxantrone-conjugated magnetic nanosystem for targeted therapy of folate receptor-overexpressing malignant cells.

BACKGROUND: Targeted delivery of anticancer chemotherapeutics such as mitoxantrone (MTX) can significantly intensify their cytotoxic effects selectively in solid tumors such as breast cancer. In the current study, folic acid (FA)-armed and MTX-conjugated magnetic nanoparticles (MNPs) were engineered for targeted eradication of folate receptor (FR)-positive cancerous cells. Polyethylene glycol (PEG), FA and MTX were covalently conjugated onto the MNPs to engineer the PEGylated FA-MTX-MNPs. The internalization studies were performed using fluorescein isothiocyanate (FITC)-labeled FA-decorated MNPs (FA-FITC-MNPs) in both FR-positive MCF-7 cells and FR-negative A549 cells by means of fluorescence microscopy and flow cytometry. The cellular and molecular impacts of FA-MTX-MNPs were examined using trypan blue cell viability and FITC-labeled annexin V apoptosis assays and 4',6-diamidino-2-phenylindole (DAPI) staining, DNA ladder and quantitative polymerase chain reaction (qPCR) assays. RESULTS: The FR-positive MCF-7 cells showed significant internalization of the FA-FITC-MNPs, but not the FR-negative A549 cells. The FR-positive cells treated with the PEGylated FA-MTX-MNPs exhibited the IC50 values of 3 μg/mL and 1.7 μg/mL, 24 h and 48 h post-treatment, respectively. DAPI staining and DNA ladder assays revealed significant condensation of nucleus and fragmentation of genomic DNA in the FR-positive MCF-7 cells treated with the PEGylated FA-MTX-MNPs as compared to the FR-negative A549 cells. The FITC-labeled annexin V assay confirmed emergence of late apoptosis (>80%) in the FR-positive MCF-7 cells treated with the PEGylated FA-MTX-MNPs, but not in the FR-negative A549 cells. The qPCR analysis confirmed profound cytotoxic impacts via alterations of apoptosis-related genes induced by MTX-FA-MNPs in MCF-7 cells, but not in the A549 cells. CONCLUSION: Our findings evince that the engineered PEGylated FA-MTX-MNPs can be specifically taken up by the FR-positive malignant cells and effectively demolish them through up-regulation of Bcl-2-associated X protein (Bax) and Caspase 9 and down-regulation of AKt. Hence, the engineered nanosystem is proposed for simultaneous targeted imaging and therapy of various cancers overexpressing FRs.

Transanal minimal invasive surgery for rectal lesions: should the defect be closed?

AIM: Transanal minimal invasive surgery (TAMIS) of rectal lesions is increasingly being used, but the technique is not yet standardized. The aims of this study were to evaluate peri-operative complications and long-term functional outcome of the technique and to analyse whether or not the rectal defect needs to be closed. METHOD: Consecutive patients undergoing TAMIS using the SILS port (Covidien) and standard laparoscopic instruments were studied. RESULTS: Seventy-five patients (68% male) of mean age 67 (± 15) years underwent single-port transanal surgery at three different centres for 37 benign lesions and 38 low-risk cancers located at a mean of 6.4 ± 2.3 cm from the anal verge. The median operating time was 77 (25-245) min including a median time for resection of 36 (15-75) min and for closure of the rectal defect of 38 (9-105) min. The defect was closed in 53% using interrupted (75%) or a running suture (25%). Intra-operative complications occurred in six (8%) patients and postoperative morbidity was 19% with only one patient requiring reoperation for Grade IIIb local infection. There was no difference in the incidence of complications whether the rectal defect was closed or left open. Patients were discharged after 3.4 (1-21) days. At a median follow-up of 12.8 (2-29) months, the continence was normal (Vaizey score of 1.5; 0-16). CONCLUSION: Transanal rectal resection can be safely and efficiently performed by means of a SILS port and standard laparoscopic instruments. The rectal defect may be left open and at 1 year continence is not compromised.

'Herbal' but potentially hazardous: an analysis of the constituents and smoke emissions of tobacco-free waterpipe products and the air quality in the cafes where they are served

BACKGROUND: There are limited data on the composition and smoke emissions of 'herbal' shisha products and the air quality of establishments where they are smoked. METHODS: Three studies of 'herbal' shisha were conducted: (1) samples of 'herbal' shisha products were chemically analysed; (2) 'herbal' and tobacco shisha were burned in a waterpipe smoking machine and main and sidestream smoke analysed by standard methods and (3) the air quality of six waterpipe cafes was assessed by measurement of CO, particulate and nicotine vapour content. RESULTS: We found considerable variation in heavy metal content between the three products sampled, one being particularly high in lead, chromium, nickel and arsenic. A similar pattern emerged for polycyclic aromatic hydrocarbons. Smoke emission analyses indicated that toxic byproducts produced by the combustion of 'herbal' shisha were equivalent or greater than those produced by tobacco shisha. The results of our air quality assessment demonstrated that mean PM2.5 levels and CO content were significantly higher in waterpipe establishments compared to a casino where cigarette smoking was permitted. Nicotine vapour was detected in one of the waterpipe cafes. CONCLUSIONS: 'Herbal' shisha products tested contained toxic trace metals and PAHs levels equivalent to, or in excess of, that found in cigarettes. Their mainstream and sidestream smoke emissions contained carcinogens equivalent to, or in excess of, those of tobacco products. The content of the air in the waterpipe cafes tested was potentially hazardous. These data, in aggregate, suggest that smoking 'herbal' shisha may well be dangerous to health.

Les lésions de l'intestin grêle et du côlon dans les traumatismes fermés de l'abdomen [Lesions of the small intestine and colon in blunt injuries of the abdomen].

Between 1976 and 1991, we observed lesions of the small bowel or colon in 39 patients having sustained blunt abdominal trauma. 70% of the patients presented with concomitant injuries. Except for 3 cases, all the patients presented with abdominal pain on admission. All the patients were operated on. The delay between admission and operation varied between a few minutes and 48 hours. Indication was hemoperitoneum, peritonitis or progressive abdominal pain. Overall morbidity is high, often related to associated disease. 4 patients died (mortality 10%), including 2 patients with isolated intestinal trauma who were operated on after 20 and 36 hours. Due to the lack of specific laboratory or X-ray test, we suggest a high index of suspicion for bowel lesions in blunt abdominal trauma, especially in unconscious patients. Close observation is mandatory. Indication for laparotomy must not be delayed if any doubt exists regarding the integrity of hollow viscus.

Malignant metastasizing solitary fibrous tumors of the liver: a report of three cases.

Solitary fibrous tumors are rare neoplasms of mesenchymal origin that have been reported in various other extrathoracic sites, including the liver. We present a case series of three malignant solitary fibrous tumors of the liver, occurring in two women 74 and 80 years old and one 65-year-old man. No clinical features were predictive of malignancy except the large sizes and synchronous presence of lung metastases in two of the three cases. Histological examinations revealed the presence of high pleomorphic cellularity with nuclear atypia, necrosis and high mitotic ratios. All patients died of disease progression.