Intra- and inter-rater consistency of dual assessment by radiologist and neurologist for evaluating DWI-ASPECTS in ischemic stroke.

OBJECTIVES: To estimate the intra -and inter-rater consistency of radiologist and neurologist working in pairs attributing DWI-ASPECTS (Diffusion Alberta Stroke Program Early CT Score) in patients with acute middle cerebral artery ischemic stroke referred for mechanical thrombectomy, intravenous thrombolysis or bridging therapy. METHODS: Five neurologists and 5 radiologists working in pairs and in hour period scored independently and in two reading sessions anonymized DWI-ASPECTS of 80 patients presenting with acute anterior ischaemic stroke in our center. We measured agreement between pairs using intraclass correlation coefficients (ICCs). A Fleiss kappa was used for dichotomized (0-6;7-10) and trichotomized (0-3;4-6;7-10) ASPECTS. The interrater distribution of the score in the trichotomized (0-3;4-6;7-10) ASPECTS was calculated. We determined the interrater (Cohen kappa) and intrarater (Fleiss kappa) agreement on the ASPECTS regions. RESULTS: The average DWI-ASPECTS was 6.35 (SD±2.44) for the first reading, and 6.47 (SD±2.44) for the second one. The ICC was 0.853 (95%CI, 0.798-0.896) for the interrater, and 0.862 (95%CI, 0.834-0.885) for the intrarater evaluation. Kappa coefficients were high for dichotomized (k=0.75) and trichotomized (k=0.64) ASPECTS. Evaluators agreement on the ASPECTS category (0-3), (4-6) and (7-10) was 88, 76 and 93% respectively. The anatomic region infarcted was well identified (k=0.70-0.77), except for the internal capsula (k=0.57). Interrater agreement was fair for M5 (k=0.37), moderate for internal capsula (0.52) and substantial for the other regions (0.60-0.79). CONCLUSIONS: Reliability of DWI-ASPECTS is good when determined by radiologist and neurologist working in pairs, which corresponds to our current clinical practice. However, discrepancies are possible for cut-off determination, which may impact the indication of thrombectomy, and for the determination of the exact infarcted region. Agreement to propose category (4-6) is lower than for (0-3) and (8-10) ASPECTS categories.

Strengthening good governance: exploiting synergies between the Performance of Veterinary Services Pathway and the International Health Regulations (2005).

The ability to minimise the harmful impact of biological threats relies on our capacity to rapidly detect unusual events, including the accidental or deliberate release of pathogenic or toxic agents, and immediately implement control measures. The development of this capacity for each country is the aim of the International Health Regulations (IHR) (2005), a legally binding document adopted by 196 States Parties, including all Member States of the World Health Organization (WHO). Each country's animal health sector contributes to the implementation of the IHR through surveillance, disease reporting and its response to zoonotic diseases, foodborne diseases and other events that emerge at the interface between human and animal health. The World Organisation for Animal Health (OIE) Performance of Veterinary Services (PVS) Pathway allows countries to undertake a comprehensive evaluation of their Veterinary Services and identify areas that need improvement. The OIE and WHO have conducted an in-depth analysis of the differences and synergies between the tools used by WHO to monitor the implementation of the IHR and the OIE PVS Pathway, revealing a wide range of similarities, complementarities and synergies. Taking advantage of the outcomes and outputs from the assessment and gap analysis tools used in the IHR Monitoring Framework and the OIE PVS Pathway, and exploiting the strength of these institutional frameworks, WHO and the OIE have jointly developed methods to facilitate communication between the animal health and human health sectors. This enhanced dialogue improves operational coordination and more efficiently informs policy-makers on strategic investments to strengthen their preparedness for controlling the spread of zoonotic diseases.

La faculté de minimiser l'impact néfaste des menaces biologiques dépend de la capacité des pays à détecter rapidement tout événement inhabituel, en particulier la dissémination accidentelle ou délibérée d'agents pathogènes ou toxiques, et à mettre en œuvre des mesures immédiates pour maîtriser ces événements. Le Règlement sanitaire international (RSI) (2005), un document juridiquement contraignant adopté par les 196 États parties, dont les États membres de l'Organisation mondiale de la santé (OMS) a précisément pour objectif de développer cette capacité dans chaque pays. Le secteur de la santé animale d'un pays participe à la mise en œuvre du RSI à travers une surveillance appropriée, la notification des maladies et l'adoption de mesures en cas de zoonoses, de maladies d'origine alimentaire et de tout autre événement émergeant à l'interface entre la santé humaine et la santé animale. Le Processus relatif aux performances des Services vétérinaires (Processus PVS) de l'Organisation mondiale de la santé animale (OIE) fournit aux pays la possibilité d'entreprendre une évaluation complète de leurs Services vétérinaires et d'identifier les domaines susceptibles d'être améliorés. L'OIE et l'OMS ont analysé de manière approfondie les différences et les synergies entre les outils utilisés par l'OMS pour vérifier la mise en œuvre du RSI, d'une part, et le Processus PVS de l'OIE, d'autre part, ce qui a mis en lumière de nombreuses similitudes, complémentarités et synergies. Sur la base des résultats et des données produites par les outils d'évaluation et d'analyse des écarts du Cadre de suivi du RSI et du Processus PVS de l'OIE, l'OMS et l'OIE ont exploité la puissance de ces cadres institutionnels pour mettre au point conjointement des méthodes visant à améliorer la communication entre les secteurs de la santé animale et de la santé humaine. Ce dialogue renforcé a pour effets d'améliorer la coordination opérationnelle et d'informer plus efficacement les décideurs politiques sur les investissements stratégiques permettant de mettre en place les conditions de préparation nécessaires pour lutter contre la propagation des zoonoses.

La aptitud de reducir al mínimo los efectos perjudiciales de las amenazas biológicas depende de nuestra capacidad para detectar con rapidez episodios inusuales, como la liberación accidental o deliberada de agentes patógenos o tóxicos, e instituir de inmediato medidas de control. El Reglamento Sanitario Internacional (RSI) (2005) es un documento jurídicamente vinculante aprobado por 196 Estados Partes, entre ellos todos los Estados Miembros de la Organización Mundial de la Salud (OMS), que precisamente tiene por objetivo dotar de esta capacidad a todos y cada uno de los países. El sector zoosanitario de cada país contribuye a la aplicación del RSI con actividades de vigilancia, notificación de enfermedades y respuesta ante enfermedades zoonóticas, enfermedades de transmisión alimentaria u otros episodios que puedan darse en la interfaz de la salud humana con la sanidad animal. El proceso de evaluación de las prestaciones de los Servicios Veterinarios (Proceso PVS) de la Organización Mundial de la Salud (OIE) sirve a los países para llevar a cabo una evaluación completa de sus Servicios Veterinarios y determinar aquellos ámbitos en que se requieran mejoras. La OIE y la OMS han analizado a fondo las diferencias y sinergias existentes entre las herramientas que utiliza la OMS para seguir de cerca la aplicación del RSI y el Proceso PVS de la OIE, labor que ha puesto de relieve un buen número de semejanzas, sinergias y aspectos complementarios de diversa índole. Partiendo de los resultados y productos que deparan las herramientas de evaluación y análisis de carencias utilizadas en el Marco de seguimiento del RSI y el Proceso PVS de la OIE, y aprovechando la solidez de estos marcos institucionales, la OMS y la OIE han definido conjuntamente métodos para facilitar la comunicación entre los sectores de la salud humana y la sanidad animal. La existencia de un diálogo más fluido se traduce en una mejor coordinación operativa y permite informar con más eficacia a los planificadores de las inversiones estratégicas necesarias para reforzar las medidas de preparación destinadas a controlar la propagación de enfermedades zoonóticas.

Patient eligibility for thrombectomy after acute stroke: Northern French Alps database analysis.

BACKGROUND: Since 2015, the emergence of mechanical thrombectomy as standard care in acute stroke has involved organizational changes not only for stroke centers, but also for entire emergency regional networks. The aim of our study was to assess the proportion of ischemic stroke patients, admitted to stroke units in the Northern French Alps within the first 6h of onset, eligible for thrombectomy. METHODS: This study retrospectively analyzed the clinical and radiological data of all acute stroke patients hospitalized at three stroke units of the Northern French Alps Emergency Network (RENAU) in 2014. Eligible patients had proximal arterial occlusions of the anterior and posterior cerebral circulation, as confirmed by brain imaging, which could be treated by thrombectomy within 6h of symptom onset. RESULTS: Of the 435 cases of acute ischemic stroke, 152 patients were treated by intravenous thrombolysis (IV rtPA). Of these patients, 83 (55%) had intracranial occlusions and were eligible for combined thrombectomy. Of the 283 patients not treatable by IV rtPA, 32 patients (11%) were eligible for primary thrombectomy. CONCLUSION: Thrombectomy could be performed in 26% of our acute ischemic stroke patients (n=115/435), and a large increase in endovascular procedures is expected over the next few years that will require close collaboration among all partners in the emergency networks. Using our RENAU stroke database, it will be possible to compare various factors contributing to effective activity.

Epidemiological, clinical, paraclinical and molecular study of a cohort of 102 patients affected with autosomal recessive progressive cerebellar ataxia from Alsace, Eastern France: implications for clinical management.

While Friedreich's ataxia (FRDA) and ataxia telangiectasia (AT) are known to be the two most frequent forms of autosomal recessive cerebellar ataxia (ARCA), knowledge on the other forms of ARCA has been obtained only recently, and they appear to be rarer. Little is known about the epidemiological features and the relative frequency of the ARCAs and only few data are available about the comparative features of ARCAs. We prospectively studied 102 suspected ARCA cases from Eastern France (including 95 from the Alsace region) between 2002 and 2008. The diagnostic procedure was based on a sequential strategic scheme. We examined the clinical, paraclinical and molecular features of the large cohort of patients and compared features and epidemiology according to molecular diagnosis. A molecular diagnosis could be established for 57 patients; 36 were affected with FRDA, seven with ataxia plus oculomotor apraxia type 2 (AOA2), four with AT, three with ataxia plus oculomotor apraxia type 1 (AOA1), three with Marinesco-Sjögren syndrome, two with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), one with ataxia with vitamin E deficiency (AVED) and one with autosomal recessive cerebellar ataxia type 2 (ARCA2). The group of patients with no identified mutation had a significantly lower spinocerebellar degeneration functional score corrected for disease duration (SDFS/DD ratio; p = 0.002) and comprised a significantly higher proportion of cases with onset after 20 years (p < 0.01). Extensor plantar reflexes were rarer and cerebellar atrophy was more frequent in the group of patients with a known non-Friedreich ARCA compared to all other patients (p < 0.0001 and p = 0.0003, respectively). Lower limb areflexia and electroneuromyographic evidences of peripheral neuropathy were more frequent in the Friedreich ataxia group than in the group with a known non-Friedreich ataxia and were more frequent in the later group than in the group with no identified mutation (p = 0.0001 and p = 0.01, respectively). The overall prevalence of ARCA in Alsace is 1/19,000. We can infer the prevalence of FRDA in Alsace to be 1/50,000 and infer that AT is approximately eight times less frequent than FRDA. MSS, AOA2 and ARSACS appear only slightly less frequent than AT. Despite the broad variability of severity, Friedreich ataxia patients are clinically distinct from the other forms of ARCA. Patients with no identified mutation have more often a pure cerebellar degenerative disease or a spastic ataxia phenotype. It appears that ARCA cases can be divided into two major groups of different prognosis, an early-onset group with a highly probable genetic cause and an adult-onset group with better prognosis for which a genetic cause is more difficult to prove but not excluded. ARCAs are rare, early-disabling and genetically heterogeneous diseases dominated by FRDA. Several of the recently identified ARCAs, such as AVED, ARSACS, AOA1, AOA2 and MSS, have a prevalence close to AT and should be searched for extensively irrespective of ethnic origins. The strategic scheme is a useful tool for the diagnosis of ARCAs in clinical practice.

[TIMMA: Ultrasonographic scale of carotid atherosclerosis by vascular neurologists]. / TIMMA : échelle échographique de la surcharge athéromateuse en carotide pratiquée par des neurologues vasculaires.

BACKGROUND: Carotid atherosclerosis is a powerful predictive factor of vascular risk at the individual patient level. Ultrasonography is a reference technique for the evaluation of this condition. However, its use in common practice remains difficult due to a lack of standardization and inter-operator variability. We present a new and simple technique for the assessment of carotid atherosclerosis; and evaluate the ability of vascular neurologists to obtain results consistent with those of an expert in vascular ultrasound. MATERIAL AND METHODS: The TIMMA scale is an acronym for the five classes of carotid atherosclerosis in French, VIMMA in English: very important, important, moderate, minimal and absent. Combined, the first two classes make up the group "significant atheroma" and the last three classes make up the group "no significant atheroma". This scale was evaluated in 38 patients (76 carotid arteries) suffering from ischemic stroke or transient ischemic attack by five operators who are competent in carotid echocardiography: one TIMMA-trained (40 hours of training) vascular neurologist physician (VNP), three VNPs informed on the measurement method (1 hour of information) and one specialized vascular physician (SVP) who was considered to be the reference examiner. We evaluated the concordance between the VNPs and the SVP in classifying patients, firstly into the significant or not atheroma group and, secondly, into the five TIMMA classes. RESULTS: The evaluation of the two-group clustering scale found a concordance between the informed VNPs and the SVP on 76 carotid arteries of 86% (kappa=0.7) and between the trained VNP and the SVP on 58 carotid arteries of 90% (kappa=0.8). The positive and negative predictive values for significant atheroma diagnosis were 100% and 81%, respectively, for the informed VNPs, and 100% and 80% for the trained VNP. The evaluation of the Five-Class Scale showed a concordance between the informed VNPs and the SVP of 46% (kappa=0.3), and between the trained VNP and the SVP of 74% (kappa=0.7). CONCLUSION: TIMMA allows VNPs who are competent in carotid ultrasonography to reproducibly identify subjects with significant carotid atheroma. The contribution of this scale to the determination of cardiovascular risk should be evaluated.

Network visualization for outbreak response: Mapping the Ebola Virus Disease (EVD) chains of transmission in N'Zérékoré, Guinea.

BACKGROUND: During the 2014-2015 Ebola Virus Disease (EVD) outbreak in N'Zérékoré, Forested Guinea, modes of transmission remained unexamined for a number of new cases. We used network visualization to investigate EVD transmission chains (TC) in seven sub-prefectures of N'Zérékoré in order to adapt outbreak response. METHODS: Between August 2014 and February 2015, the EVD outbreak response team including the World Health Organization (WHO) and local health authorities routinely collected information among new cases regarding hospital visits, cases within a household, participation in burials, as well as dates of symptom onset, serial intervals (SI) and exposure to EVD. SI's were defined as the interval between symptom onset in an index case and symptom onset in a secondary case infected by that index case. Cases who reported hospital visits, contact with a case in the household or participating in burials were attributed to these exposures. RESULTS: We identified seven TC (two urban and five rural) gathering characteristics of 109 probable/confirmed cases. Overall, 61% (66 cases, SI range: 7-20 days) were household related, 32% (35 cases, SI range 8-30 days) were household or burial related and 7% (8 cases, SI range: 4-20 days) were hospital-related. In the urban chains (18 cases, SI range: 7-20 days), 12 cases were household related and 6 cases were hospital related, none where household or burial related. In the rural chains (84 cases, SI range: 7-30 days), 60% (50 cases) were household related, 1% (1 case) was hospital related and 39% (34 cases) were household or burial related. No cases reported multiple exposures. CONCLUSIONS: Network visualization during field response is crucial in enhancing local control strategies, refining outbreak response and aiding rapid response teams in insuring psychosocial and socio-economic recovery. Urban settings need to focus on reducing hospital EVD transmission whereas rural settings should focus on raising awareness of transmission within a household and safeguarding EVD burials.

Implementing the International Health Regulations (2005) in Europe.

The adoption of the International Health Regulations (2005) (also referred to as IHR(2005) or the revised Regulations) provides a remarkable new legal tool for the protection of international public health. Upon entry into force on 15 June 2007, Article 2 ('Purpose and scope') provides that the overall focus of the efforts of States Parties (and World Health Organization's efforts under the revised Regulations will be to prevent, protect against, control and provide a public health response to the international spread of disease in ways that are commensurate with the public health risks and which avoid unnecessary interference with international traffic. Health measures under the revised Regulations will be implemented with respect for travellers' human rights, with several specific new requirements in this area. To comply with the IHR(2005), States Parties (WHO member states that will be bound by the IHR(2005)) will have to have core public health capacities in disease surveillance and response, as well as additional capacities at designated international ports, airports and land crossings. This unique collective commitment will require close collaboration between WHO and the States Parties, but also intersectoral collaboration within the States themselves, including collaboration among different administrative or governmental levels, a particular issue for federal states, and horizontally across ministries and disciplines. Collaboration among States Parties is a key aspect of the revised Regulations, whether among neighbours, or with trading partners, members of regional economic integration organisations or other regional groups, or simply members of the international community. This collaboration is particularly relevant for the Member States of the European Union.

Two clusters of human infection with influenza A/H5N1 virus in the Republic of Azerbaijan, February-March 2006.

Following the appearance of influenza A/H5 virus infection in several wild and domestic bird species in the Republic of Azerbaijan in February 2006, two clusters of potential human avian influenza due to A/H5N1 (HAI) cases were detected and reported by the Ministry of Health (MoH) to the World Health Organization (WHO) Regional Office for Europe during the first two weeks of March 2006. On 15 March 2006, WHO led an international team, including infection control, clinical management, epidemiology, laboratory, and communications experts, to support the MoH in investigation and response activities. As a result of active surveillance, 22 individuals, including six deaths, were evaluated for HAI and associated risk infections in six districts. The investigations revealed eight cases with influenza A/H5N1 virus infection confirmed by a WHO Collaborating Centre for Influenza and one probable case for which samples were not available. The cases were in two unrelated clusters in Salyan (seven laboratory confirmed cases, including four deaths) and Tarter districts (one confirmed case and one probable case, both fatal). Close contact with and de-feathering of infected wild swans was considered to be the most plausible source of exposure to influenza A/H5N1 virus in the Salyan cluster, although difficulties in eliciting information were encountered during the investigation, because of the illegality of some of the activities that might have led to the exposures (hunting and trading in wild birds and their products). These cases constitute the first outbreak worldwide where wild birds were the most likely source of influenza A/H5N1 virus infection in humans. The rapid mobilisation of resources to contain the spread of influenza A/H5 in the two districts was achieved through collaboration between the MoH, WHO and its international partners. Control activities were supported by the establishment of a field laboratory with real-time polymerase chain reaction (RT-PCR) capacity to detect influenza A/H5 virus. Daily door-to-door surveillance undertaken in the two affected districts made it unlikely that human cases of influenza A/H5N1 virus infection remained undetected.

Two clusters of human infection with influenza A/H5N1 virus in the Republic of Azerbaijan, February-March 2006.

Following the appearance of influenza A/H5 virus infection in several wild and domestic bird species in the Republic of Azerbaijan in February 2006, two clusters of potential human avian influenza due to A/H5N1 (HAI) cases were detected and reported by the Ministry of Health (MoH) to the World Health Organization (WHO) Regional Office for Europe during the first two weeks of March 2006. On 15 March 2006, WHO led an international team, including infection control, clinical management, epidemiology, laboratory, and communications experts, to support the MoH in investigation and response activities. As a result of active surveillance, 22 individuals, including six deaths, were evaluated for HAI and associated risk infections in six districts. The investigations revealed eight cases with influenza A/H5N1 virus infection confirmed by a WHO Collaborating Centre for Influenza and one probable case for which samples were not available. The cases were in two unrelated clusters in Salyan (seven laboratory confirmed cases, including four deaths) and Tarter districts (one confirmed case and one probable case, both fatal). Close contact with and de-feathering of infected wild swans was considered to be the most plausible source of exposure to influenza A/H5N1 virus in the Salyan cluster, although difficulties in eliciting information were encountered during the investigation, because of the illegality of some of the activities that might have led to the exposures (hunting and trading in wild birds and their products). These cases constitute the first outbreak worldwide where wild birds were the most likely source of influenza A/H5N1 virus infection in humans. The rapid mobilisation of resources to contain the spread of influenza A/H5 in the two districts was achieved through collaboration between the MoH, WHO and its international partners. Control activities were supported by the establishment of a field laboratory with real-time polymerase chain reaction (RT-PCR) capacity to detect influenza A/H5 virus. Daily door-to-door surveillance undertaken in the two affected districts made it unlikely that human cases of influenza A/H5N1 virus infection remained undetected.

[Emergent pathogens, international surveillance and international health regulations (2005)]. / Les pathogènes émergents, la veille internationale et le Règlement sanitaire international (2005).

In order to address the vitality of the microbial world, to detect emerging infectious diseases, to determine their potential threat to public health, and to establish effective interventions, the World Health Organization (WHO) has developed and coordinates the Global Outbreak Alert and Response Network (GOARN) which connects several surveillance networks. Some of these networks are specific to epidemic-prone diseases, such as influenza, dengue, yellow fever or meningitis. Others were especially designed to track unusual events--such as the emergence of SARS--that are naturally-occurring, accidental, or deliberately created (biological weapons, bio-terrorism). Lastly, a special effort is being made at the international level to modernize the International Health Regulations, now obsolete, and to support all the countries in the reinforcement of their outbreak alert and response capacity.

[Epidemiological aspects of Ebola virus disease in Guinea (december 2013-april 2016)]. / Aspects épidémiologiques de la maladie à virus Ebola en Guinée (décembre 2013­avril 2016).

Ebola Zaire species variant Makona between its emergence in December 2013 and April 2016, resulted in an epidemic of Guinea importance and unprecedented gravity with 3814 reported cases of which 3358 were confirmed (88.0%) and 2544 were died (66.7%). The epidemic has evolved in phases: a silent phase without identification of all fatal cases until February 2014; a first outbreak from March 2014, when the alarm is raised and the virus detected, which lasted until July 2014; a second increase, which was the most intense, from August 2014 to January 2015 focused primarily on the forest Guinea; and a final increase from February 2015 centered on lower Guinea and the capital Conakry. Adapting strategies in 2015 (initiative "Zero Ebola in 60 days" active case search and suspicious deaths and awareness of active prefectures, microbanding the last affected communities and raking around these localities) and ring vaccination of contacts around confirmed cases has allowed to gradually control the main outbreak in October 2015. But a survivor was originally resurgence in forest areas between March and April 2016 with 10 cases including 8 deaths. The epidemic has particularly affected the forest Guinea region (44% and 48% of Guinean cases and deaths), elderly women (≥ 50 years), and health professionals (211 cases including 115 deaths); however, almost one-third of the patients (32.6%) was not provided supportive care in the Ebola centers. The epidemic is currently marked by the resurgence of small foci, from excreting subjects cured of the virus who have been controlled so far successfully. The survivors are the subject of special attention. It is necessary to learn lessons from the response to better prepare for the future, to improve knowledge about the natural history of the Ebola virus disease, and to rethink communication in this regard with the public and its leaders.

Social and cultural factors behind community resistance during an Ebola outbreak in a village of the Guinean Forest region, February 2015: a field experience.

BACKGROUND: During the Ebola outbreak in Guinea, community resistance obstructed case investigation and response. We investigated a cluster of Ebola cases that were hiding in the forest, refusing external help, to identify sociocultural determinants related to community resistance. METHODS: Participant observation, interviews and focus group discussions were carried out. RESULTS: Most villagers feared the Ebola treatment centre (ETC) as there was the belief that people were killed in ETCs for organ trade. Four survivors accompanied back to the village from the ETC shared their experiences and reassured their neighbours. Subsequently, community compliance with contact tracing improved, leading to the timely detection of cases. CONCLUSIONS: Engaging Ebola virus disease survivors improved community compliance. Understanding the sociocultural context and community perceptions may improve community engagement and prevent Ebola virus transmission.

Glicentin and oxyntomodulin modulate both the phosphoinositide and cyclic adenosine monophosphate signaling pathways in gastric myocytes.

We have investigated the transduction pathways mediating the contractile effect of two glucagon-containing peptides, glicentin (GLIC) and oxyntomodulin (OXM), on smooth muscle cells isolated from rabbit antrum. Low concentrations of GLIC induced a biphasic and rapid (first phase at 5-8 sec) Ins(1,4,5)P3 production. By comparison, higher concentrations of OXM or OXM(19-37) were required to obtain biphasic time-courses of Ins(1,4,5)P3 production. In a Ca2+ free medium, the first phase of Ins(1,4,5)P3 production induced by GLIC or OXM was maintained, while the second phase disappeared. In saponin-permeabilized cells, all three peptides induced cell contraction with similar efficacies and potencies. Exogenous Ins(1,4,5)P3 mimicked the contractile effect of the peptides and heparin, which inhibits the Ins(1,4,5)P3 binding to its receptor, prevented contraction stimulated by each effector. We conclude that a Ca2+ mobilization from the intracellular stores is essential in the contractile effects of GLIC and OXM. Using the fluo-3 probe, a [Ca2+]i increase was observed in the presence of GLIC, OXM, or OXM(19-37). The three peptides reduced by 30-40% the cAMP content of cells stimulated by forskolin. This effect was pertussis toxin sensitive as demonstrated with OXM(19-37). Our data constitute important clues for the existence in smooth muscle cells of receptor(s) specific for the GLIC/OXM hormones, coupled via G protein(s) to both Ca2+ and cAMP pathways.

Secretion of insulin-like growth factors and their binding proteins by human normal and hyperplastic prostatic cells in primary culture.

Benign prostatic hyperplasia (BPH) is the most common benign proliferative disorder of unknown etiology found in men. Because insulin-like growth factors (IGFs) with their binding proteins (IGFBPs) are involved in the control of cellular proliferation, differentiation, and metabolism, we compared their secretion by prostatic epithelial and stromal cells in primary culture from the four different zones of normal prostate and from hyperplastic tissue to assess their contributions to the hyperplastic development. IGF-I could not be detected in the conditioned medium from either epithelial or stromal cells from normal and BPH tissues. IGF-II concentrations were the same in the conditioned medium from the epithelial cells of the different zones of the normal prostate and that of BPH cells. IGF-II concentrations secreted in stromal cell culture medium, however, were higher in the periurethral zone than in the peripheral and central zones. Moreover, in the periurethral zone, stromal cells secreted higher concentrations of IGF-II than did epithelial cells. Also, BPH stromal cells secreted more IGF-II than did BPH epithelial cells. IGFBP-3, IGFBP-2, and IGFBP-4 were all secreted by both epithelial and stromal cells. In contrast, IGFBP-5 was only produced by stromal cells of the periurethral zone of the normal prostate and BPH tissue. IGFBP-3 was predominantly secreted by normal stromal cells of the transitional zone. We observed that BPH stromal cells presented the same pattern of IGF-II and IGFBP production as normal stromal cells of the periurethral zone. These data support the hypothesis that the periurethral zone is the main region of the prostate implicated in the development of BPH. They also suggest that the variability in both IGF-II secretion and the secreted forms of IGFBPs, depending on anatomical location within the organ, may be important for the autocrine regulation of normal and hyperplastic prostate growth.

Hot spots in a wired world: WHO surveillance of emerging and re-emerging infectious diseases.

The resurgence of the microbial threat, rooted in several recent trends, has increased the vulnerability of all nations to the risk of infectious diseases, whether newly emerging, well-established, or deliberately caused. Infectious disease intelligence, gleaned through sensitive surveillance, is the best defence. The epidemiological and laboratory techniques needed to detect, investigate, and contain a deliberate outbreak are the same as those used for natural outbreaks. In April 2000, WHO formalised an infrastructure (the Global Outbreak Alert and Response Network) for responding to the heightened need for early awareness of outbreaks and preparedness to respond. The Network, which unites 110 existing networks, is supported by several new mechanisms and a computer-driven tool for real time gathering of disease intelligence. The procedure for outbreak alert and response has four phases: systematic detection, outbreak verification, real time alerts, and rapid response. For response, the framework uses different strategies for combating known risks and unexpected events, and for improving both global and national preparedness. New forces at work in an electronically interconnected world are beginning to break down the traditional reluctance of countries to report outbreaks due to fear of the negative impact on trade and tourism. About 65% of the world's first news about infectious disease events now comes from informal sources, including press reports and the internet.

Seroprevalence survey of Egyptian tourism workers for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and Treponema pallidum infections: association of hepatitis C virus infections with specific regions of Egypt.

Blood samples from 740 Egyptian Nationals working in the tourism industry at two sites in the South Sinai governorate were screened for markers of infection with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and Treponema pallidum. Study subjects included 467 individuals from a rural seashore tourist village and 273 persons at two hotels in a well-established resort town. Subjects' ages ranged from 15 to 70 years; 99.3% were male. The prevalence of serologic markers for currently asymptomatic or past HBV infection alone was 20.7% (n = 153), of markers for past or chronic HCV infection alone was 7.4% (n = 55), and of markers for both HBV and HCV was 6.9% (n = 51). Of the 204 individuals positive for anti-HBV core antibody, 12 (5.9%) were also positive for hepatitis B surface antigen. Two individuals (0.3%) had a serologic market suggestive of an active syphilitic infection. No subject was found to be HIV-seropositive. History of prior injections and number of injections were associated with infection with HCV. Primary residence in the Nile delta and valley areas where schistosomiasis is highly endemic, was also a statistically significant risk factor for HCV, but not HBV infection.

PIP: In June 1994, in Egypt, a physician, a laboratory technician, and a recorder surveyed 740 nationals aged 15-70 years, 99.3% of whom were male, who worked in the local tourist industry of the South Sinai governorate (a rural seashore tourist village and a well-established tourist town). Researchers aimed to determine the prevalence of past or chronic infections with hepatitis B virus (HBV), hepatitis C virus (HCV), HIV, and Treponema pallidum (syphilis) in tourist workers and to identify risk factors for infection with these pathogens. Condoms were used and safer sex was practiced in about 90% of casual sexual encounters. No tourist worker tested positive for HIV-1 or HIV-2 infection. 0.3% had active syphilis. 27.6% of the tourist workers tested positive for HBV. 1.6% (5.9% of HBV-positive workers) were positive for hepatitis B surface antigen, indicating an asymptomatic HBV infection. 14.3% of all tourist workers tested positive for HCV. 6.9% tested positive for both HBV and HCV. Rural residence was a significant risk factor for HBV infection (odds ratio [OR] = 1.6; p = 0.02). Significant risk factors for HCV infection included residence in a region highly endemic for schistosomiasis (i.e., Nile delta and valley areas) (OR = 3.2; p 0.01), rural residence (OR = 2.3; p = 0.01), and more than 10 lifetime injections (OR = 2.6; p = 0.02).

Trends of human immunodeficiency virus type-1 infection in female prostitutes and males diagnosed with a sexually transmitted disease in Djibouti, east Africa.

A cross-sectional serosurvey for human immunodeficiency virus type 1 (HIV-1) was conducted during the first quarter of 1991 among high risk groups in Djibouti, East Africa, and compared with previous surveys in 1987, 1988, and 1990. The survey demonstrated evidence of HIV-1 infection in 36.0% (n = 292) of street prostitutes, 15.3% (n = 360) of prostitutes working as bar hostesses, and 10.4% (n = 193) of males diagnosed with a sexually transmitted disease. By multivariate modeling, HIV-1 seropositivity in prostitutes was associated with Ethiopian nationality, working as a street prostitute, and residing in Djibouti for two years or less. We suggest that prostitution, particularly street prostitution, is a major route of HIV-1 transmission in Djibouti.

PIP: Findings from a cross-sectional serosurvey for HIV-1 conducted in 1991 are compared with data from previous surveys conducted in 1987, 1988, and 1990. This most recent study was conducted in the 1st quarter of 1991 among a total 845 individuals belonging to high-risk groups in Djibouti, East Africa. The 1987, 1988, and 1990 surveys respectively sampled 539, 582, and 402 subjects. Individuals were sampled consecutively as they visited the public sexually transmitted diseases (STD) clinic. HIV infection was found in 36.0% of 292 street prostitutes, 15.3% of 360 prostitutes working as bar hostesses, and 10.4% of 193 males diagnosed with a STD. The estimated 1500 women engaged in prostitution in the country with no legal occupation are considered to be street prostitutes. Multivariate modeling found HIV infection in prostitutes to be associated with Ethiopian nationality, working as a street prostitute, and residing in Djibouti for 2 years or less. The prevalence of HIV-1 among street prostitutes was markedly greater than the 4.6% in 1987, yet down from 41.7% in 1990. The authors note that street prostitution is a major route of HIV transmission in Djibouti.

Serologic evidence of respiratory and rickettsial infections among Somali refugees.

Somali refugees living in a camp located in Djibouti were studied in October 1991 and May 1992. The refugees had been living at the camp for about two years. The median age of volunteers was 25 years, of whom 69% were female. Paired sera obtained seven months apart were evaluated by complement fixation, microimmunofluorescence, indirect fluorescent antibody, streptococcal antibody, and enzyme-linked immunosorbent assay techniques for evidence of pathogen infection. Fifty-two percent, 31.3%, 8.0%, 5.9%, and 25.4% of the volunteers had serologic evidence for pre-enrollment infection with Chlamydia pneumoniae, Mycoplasma pneumoniae, Rickettsia typhi, R. conorii, and Coxiella burnetti, respectively. Similarly, 43.5%, 5.2%, 6.1%, 10.7%, 15.8%, and 11.9% of the volunteers studied had serologic evidence for new infection with Streptococcus pyogenes, C. pneumoniae, M. pneumoniae, R. typhi, R. conorii, and Cox. burnetii, respectively. These data suggest that the studied pathogens may be endemic in displaced populations living in the Horn of Africa.

Neurobehavioral changes following bilateral infarct in the caudate nuclei: a case report with pathological analysis.

A patient presenting with loss of psychic self activation (LPSA) was studied clinically and at autopsy. Clinically, the patient showed changes that can be ascribed to the interruption of frontal-subcortical circuits. Pathological analysis revealed bilateral lesions of the caudate nuclei. This case extends others based on radiological findings and confirms the importance of the caudate nuclei in behavioral functions.

HHV-6 in Djibouti--an epidemiological survey in young adults.

Human herpesvirus type six (HHV-6), previously called human B-cell lymphotropic virus (HBLV), was first isolated in 1986 from patients with various lymphoproliferative disorders, some related to the acquired immunodeficiency syndrome. In order to investigate the epidemiology of HHV-6 in the Horn of Africa, we studied 281 young adults living in the city of Djibouti during June 1988. Of these, 181 belonged to various groups at risk for human immunodeficiency virus (HIV), while 100 represented the normal young adult population. Sera were screened and titrated for antibodies against HHV-6 by an indirect fluorescent antibody assay. The percentage seropositivity for HHV-6 was 71 in the normal population, 75 in the population at risk for HIV, and 93 in the population of subjects with a confirmed positive HIV Western blot. Mean titres of positive sera were similar in all population groups. No correlation existed between HHV-6 seropositivity and age, sex, tribe, habitat, and risk factors for HIV. A positive correlation was noted between HHV-6 and patients complaining of fatigue.