New tree-ring data from Canadian boreal and hemi-boreal forests provide insight for improving the climate sensitivity of terrestrial biosphere models.

Understanding boreal/hemi-boreal forest growth sensitivity to seasonal variations in temperature and water availability provides important basis for projecting the potential impacts of climate change on the productivity of these ecosystems. Our best available information currently comes from a limited number of field experiments and terrestrial biosphere model (TBM) simulations of varying predictive accuracy. Here, we assessed the sensitivity of annual boreal/hemi-boreal forest growth in Canada to yearly fluctuations in seasonal climate variables using a large tree-ring dataset and compared this to the climate sensitivity of annual net primary productivity (NPP) estimates obtained from fourteen TBMs. We found that boreal/hemi-boreal forest growth sensitivity to fluctuations in seasonal temperature and precipitation variables changed along a southwestern to northeastern gradient, with growth limited almost entirely by temperature in the northeast and west and by water availability in the southwest. We also found a lag in growth climate sensitivity, with growth largely determined by the climate during the summer prior to ring formation. Analyses of NPP sensitivity to the same climate variables produced a similar southwest to northeast gradient in growth climate sensitivity for NPP estimates from all but three TBMs. However, analyses of growth from tree-ring data and analyses of NPP from TBMs produced contrasting evidence concerning the key climate variables limiting growth. While analyses of NPP primarily indicated a positive relationship between growth and seasonal temperature, tree-ring analyses indicated negative growth relationships to temperature. Also, the positive effect of precipitation on NPP derived from most TBMs was weaker than the positive effect of precipitation on tree-ring based growth: temperature had a more important limiting effect on NPP than tree-ring data indicated. These mismatches regarding the key climate variables limiting growth suggested that characterization of tree growth in TBMs might need revision, particularly regarding the effects of stomatal conductance and carbohydrate reserve dynamics.

Medical check-up of newly arrived unaccompanied minors: A dedicated pediatric consultation service in a hospital.

BACKGROUND AND AIMS: Healthcare for the increasing number of migrants in Europe, and particularly of unaccompanied minors (UMs) seeking asylum, has become a major challenge. We aimed to describe the health issues of UMs managed in a dedicated pediatric consultation service in a care center in Paris. METHODS: All UMs attending a dedicated migrant medical consultation service in Robert Debré Hospital, Paris, France, were included in a single-center retrospective observational study from September 1, 2017, to September 30, 2018. RESULTS: Out of the 107 UMs who were included, 87% had a health problem (n=93) and 52% had an infectious disease (n=56). The main infectious diagnoses were schistosomiasis (22%), latent tuberculosis (22%), intestinal parasitosis (16%), and chronic hepatitis B (8%). Posttraumatic stress disorder (PTSD) and overweight were common (35% and 20%, respectively). The median age was 15 years old (IQR, 14-16), the male/female ratio was 95/12. Most of the children were from sub-Saharan Africa (n=67), 46% had crossed Libya (n=49) and, when compared to the other migration routes, faced an increasing risk of violence (69%, p=0.04), imprisonment (53%, p=0.03), and forced labor (48%, p=0.02). The median duration of the trip before reaching France was 6 months (IQR, 2-13), the median time to consultation was 2 months (0-5) and was not associated with an increased risk of health problems. A total of 43 UMs were lost to follow-up. CONCLUSION: Health problems, particularly infectious diseases and PTSD, are common among UMs and should prompt an early medical consultation with psychiatric evaluation. Follow-up is problematic and could be improved by an on-line health book.

Long-term assessment of effectiveness and quality of life of OnabotulinumtoxinA injections in provoked vestibulodynia.

BACKGROUND: Provoked vestibulodynia is a relatively common condition that affects sexual activity. Multidisciplinary care is indicated and OnabotulinumtoxinA injections are safe and effective treatment in this indication. AIMS: To assess the long-term efficacy of OnabotulinumtoxinA in provoked vestibulodynia. MATERIALS AND METHODS: Twenty-one patients treated with OnabotulinumtoxinA injections (50U in each bulbospongiosus muscle) 24 months prior to the study were included. Data on pain [assessed using a visual analogue scale (VAS)], quality of life [measured by the Dermatology Life Quality Index (DLQI)] and quality of sex life [assessed using the Female Sexual Function Index (FSFI)] were collected before treatment, and 3 and 24 months after injection. RESULTS: Nineteen patients participated in the study and 37% had no pain after 24 months. Significant improvements were noted in the VAS, DLQI and FSFI scores between baseline and 24 months post treatment (P < 0.0001). After 24 months, 18 patients (95%) were able to have sexual intercourse. This study was open and non-controlled. DISCUSSION AND CONCLUSION: 100U OnabotulinumtoxinA injections constitute an effective treatment in provoked vestibulodynia with results maintained after 2 years. They significantly improve pain, and have a positive impact on patient quality of life and sex life. Beneficial effects continue in the long-term, allowing patients to resume sexual activity.

[Vulvar oedema revealing systemic mastocytosis]. / Œdème vulvaire révélant une mastocytose systémique.

BACKGROUND: Systemic mastocytosis is characterised by abnormal proliferation of mast cells in various organs. We report an original case of systemic mastocytosis revealed by vulvar oedema. PATIENTS AND METHODS: A 24-year-old patient was examined in the dermatology department for vulvar oedema appearing during sexual intercourse. She presented vasomotor dysfunction of the lower limbs, urticaria on the trunk on exertion, diarrhoea and bone pains. Laboratory tests showed serum tryptase of 29.7µg and plasma histamine at twice the normal value. Myelogram results showed infiltration by dysmorphic mast cells. Screening for c-kit D816V mutation was positive. Duodenal biopsies revealed mast-cell clusters with aggregation involving over 15 mast cells. CD2 staining was inconclusive and CD25 staining could not be done. Trabecular osteopenia was found, and we thus made a diagnosis of indolent systemic mastocytosis (ISM variant Ia) as per the WHO 2008 criteria. Symptomatic treatment was initiated (antiH1, H2, antileukotrienes) and clinical and laboratory follow-up was instituted. DISCUSSION: The cutaneous signs leading to diagnosis in this patient of systemic mastocytosis involving several organs were seemingly minimal signs associated with mastocyte degranulation. This is the third recorded case of mastocytosis revealed by vulvar oedema and the first case revealing systemic involvement. The two previously reported cases of vulvar oedema revealed cutaneous mastocytosis alone. Mastocytosis, whether systemic or cutaneous, must be included among the differential diagnoses considered in the presence of vulvar oedema.

[Bilateral spontaneous carotid-cavernous fistula revealing Ehler-Danlos disease]. / Fistules carotido-caverneuses spontanées bilatérales révélant une maladie d'Ehlers-Danlos de type IV.

PATIENTS AND METHODS: A 34-year-old woman with an extensive surgical history developed two spontaneous carotido-cavernous fistula bilaterally. Skin examination revealed an acrogeric form of vascular Ehlers-Danlos syndrome and this diagnosis was confirmed by genetic analysis. DISCUSSION: Vascular Ehlers-Danlos syndrome is a rare autosomal dominant genetic disease that may be suspected on the grounds of clinical symptoms. Severe complications can occur in early life and are associated with a high mortality rate. The prognosis of vascular Ehlers-Danlos syndrome has been radically changed by the use of beta-blockers. CONCLUSION: The originality of our observation lies in the long time to onset of the initial complications in the absence of any problems during the numerous operations undergone by the patient, as well as the two childbirths.

[The role of probiotics in the treatment of inflammatory bowel diseases]. / Place des probiotiques dans le traitement des maladies inflammatoires intestinales.

The intestinal mucosa is the site of a fundamental interaction between a large amount of foreign substances, the immune system and bacteria that colonizes the mucosa. Many gastrointestinal diseases are due to an altered interaction between all these actors, particularly inflammatory bowel diseases. As such probiotics (bacteria providing a benefit to the host) could provide an interesting solution as a therapeutic agent. The evidences supporting such use are limited but there are still some quality randomized controlled trials. The purpose of this review is to discuss the most recent evidences from the literature on the use of probiotics in the treatment of inflammatory bowel diseases.

Highly sensitive, quick and simple quantification method for mono and disaccharides in aqueous media using liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS).

A highly sensitive, rapid LC-APCI-MS method for identification and quantification of mono and disaccharides in simple or complex aqueous phase has been developed. This original method is easy to use, no derivation and no post-column injection are needed. The separation is performed with a hydrophilic amino interaction (HILIC) column allowing high-throughput analysis with analysis times of 15 min for monosaccharides to 22 min for disaccharides. The development of the method carried out with 9 standard saccharides allowed to point out a dynamic range from 0.1-25.6 to 1-256 µg mL(-1) depending on the considered sugar. Next, the method was validated on saccharides at known concentrations in water and on 2 real samples: orange juice and aqueous phase obtained after enzymatic hydrolysis of sunflower seeds.

Development of a fish-based index to assess the ecological quality of transitional waters: the case of French estuaries.

The Water Framework Directive requires the assessment of the ecological status of transitional waters considering the fish component. An original methodology, based on a pressure-impact approach, was established to develop a multimetric fish-based index to characterize the ecological quality of French estuaries. An index of contamination, based on the chemical pollution affecting aquatic systems, was used as a proxy of anthropogenic pressure. The fish metric selection was based on their response to disturbances tested via statistical models (generalized linear models) taking into account sampling strategy and estuarine features. Four metrics, for which discriminating responses to level of pressure were demonstrated, were retained to constitute the estuarine multimetric fish index. This new tool appeared particularly relevant to detect the contamination effects on fish communities in estuaries. It could help managers to take decisions in order to maintain or reach the good status required by the Water Framework Directive for 2015.

[Role of endoscopy in the management of obscure gastrointestinal bleeding]. / Rôle de l'endoscopie dans la prise en charge des saignements digestifs d'origine obscure.

Obscure gastrointestinal bleeding is defined as a blood loss in the digestive tract without etiology found at upper digestive endoscopy and colonoscopy. Small bowel lesions, in particular angiodysplasias, are the most frequent cause. Endoscopic examination of the small bowel can be performed using an enteroscope (with or without balloon) or a videocapsule. Videocapsule endoscopy is a minimally invasive procedure, and it allows complete small bowel exploration in 80% of cases (vs. 40-80% with balloon-aided enteroscopy). In practice, videocapsule endoscopy is the first line exam, followed by enteroscopy for biopsy sampling or treatment. In case of completely negative investigations and persistent bleeding, videocapsule endoscopy may be repeated, generally after repeat upper digestive endoscopy and colonoscopy.

[What's new in the treatment of hepatitis B infection?]. / Quoi de neuf pour le traitement de l'hépatite B?

Although the number of available antiviral drugs for hepatitis B infection (VHB) today is higher than ever, treatment of chronic VHB infection is still often managed by specialists because of the complex natural history of this viral infection and of the risk of selecting viral strains that are resistant to therapy. Different clinical and virological aspects need to be considered to establish a correct indication for therapy. Once antiviral therapy has been started, patients need close monitoring to guarantee adequate compliance and to detect promptly the selection of viral variants resisting to therapy.

[Hepavir, the first observational study of one cohort of patients treated with alpha-2a interferon, monotherapy. Evaluation of asthenia and its social consequences]. / Hépavir, première étude observationnelle d'une cohorte de malades traités par interféron alpha-2a en monothérapie. Evaluation de l'asthénie et de ses répercussions sociales.

OBJECTIVES: The aim of this observational study in patients with chronic hepatitis C and treated with interferon alpha-2a was to assess 1) monitoring in everyday practice, 2) the acceptability of treatment and 3) the intensity of fatigue. METHODS: Three hundred and fifty four patients were enrolled by physicians in both teaching and general hospitals, or private practice. Before treatment, clinical, epidemiological, and virological data were collected as well as a self-evaluation of fatigue using a visual analogic scale. Clinical follow-up was assessed every 3 months during treatment and 6 months after the end of treatment and included an evaluation of fatigue and the number of workdays missed due to sickness. RESULTS: Two hundred and nineteen men and 135 women, mean age 45 +/- 13, were included. The epidemiological, histological and virological features of this group were similar to those patients usually treated for chronic hepatitis C. Before treatment, the mean measurement of fatigue was 41 on a scale from 0 (perfect form) to 100 (exhausted). Fatigue was unrelated to age, source of infection, biological activity, or histological score. It worsened in patients who stopped interferon after 3 or 6 months, but was stable in patients who continued treatment for 12 months. Fatigue decreased after the end of treatment and was unrelated to treatment response. The need to stop work was strongly related to the intensity of fatigue and the number of workdays missed due to sickness represented nearly two months out of three in 25% of active patients during the first quarter and in 15% of patients thereafter. 61% of patients self-injected interferon (mainly previous drug users) whereas 30% of patients used nurse care throughout treatment. CONCLUSION: This study not only provides a realistic evaluation of fatigue in patients with chronic hepatitis C, before, during and after treatment, but also highlights its social and economic consequences. It shows the need for further cost-effectiveness studies on new therapeutic strategies using combined treatments.

Does HIV-infection influence the response of chronic hepatitis C to interferon treatment? A French multicenter prospective study. French Multicenter Study Group.

BACKGROUND/AIM: The aim of this prospective study was to compare the response to alfa-interferon treatment of chronic hepatitis C in two groups of patients: coinfected with human immunodeficiency virus (HIV) (G I) or not (G II). METHODS: One hundred and fifty-three patients with chronic hepatitis C had been enrolled in 30 French liver units or infectious diseases units between May 1992 and January 1995 (G I: 76, G II: 77) to receive alfa-2a interferon: 3 MU thrice weekly for 6 months. RESULTS: One hundred and twenty-seven patients (G I: 63, G II: 64) fulfilled all criteria for analysis. The two groups were comparable for all demographic data, while significantly more severe biological and histological (p=0.001) parameters attested to more serious hepatitis among HIV-HCV coinfected patients. HCV viremia was higher among HIV-coinfected patients (p=0.0169), while genotype repartition was identical among the two groups (more than 52% of genotype 1, more than 31% of genotype 3). ALT normalization was, respectively, (G I/G II) obtained in 17.46%/26.56% (not significant) of patients at the end of treatment and in 11.11%/12.5% (not significant) of patients after 6 months of follow-up. In a multivariate analysis, GGT level before therapy (relative risk 2.1, confidence interval 1.1-5.8) and body surface area (relative risk 1.9, confidence interval 1.1-3.7) were the variables independently associated with the response to alfa-interferon treatment (higher GGT and more elevated body surface area were associated with a risk of non-response). CONCLUSION: In our study HIV infection did not affect the alfa-interferon treatment response of chronic hepatitis C, and response could be achieved among HIV-coinfected patients. Present therapeutic anti-HCV schedules need to be proposed to HIV-HCV coinfected patients before severe immunosuppression occurs. On the other hand, more severe biological and histological parameters were observed among HIV-HCV coinfected patients, which suggests a need to study whether HIV infection is associated with a worsening course of chronic hepatitis C.

Randomized trial of interferon-alpha plus ursodeoxycholic acid versus interferon plus placebo in patients with chronic hepatitis C resistant to interferon.

BACKGROUND: Ursodeoxycholic acid (UDCA) could potentiate the effect of interferon (IFN) in patients with chronic hepatitis C resistant to IFN. We compared the efficacy of IFN with that of a combination of IFN and UDCA. METHODS: Patients were randomized to receive UDCA (13-15 mg/kg/day) (n = 47) or placebo (n = 44) plus interferon (3 MU three times weekly) for 6 months and were then followed up for 6 additional months. RESULTS: At entry 30% of patients had cirrhosis, and 70% had HCV genotype 1. Five and four patients withdrew from the combination and the monotherapy groups, respectively. At 6 months alanine aminotransferase (ALAT) and gamma-glutamyl transferase (GGT) activities were significantly lower (P < 0.001) in the combination group than in the monotherapy group; the differences were no longer significant at 1 year. At 6 months ALAT activities normalized in 10 and 8 patients in the combination and the monotherapy groups, respectively (P = 0.67). In 10 of them (5 in each group) HCV RNA levels became undetectable. At 1 year four versus one patient had a sustained normalization of ALAT, and in one patient the HCV RNA became negative. There was no difference in the histologic progression. In this setting, in contrast to chronic cholestasis, UDCA administration induced an increase in total serum bile acids and did not change primary bile acids. CONCLUSIONS: An IFN plus UDCA combination is more effective than IFN alone in terms of ALAT but not in terms of the virologic response. These results favor the hypothesis that UDCA has an effect on the biochemical indices of cellular injury independent of a change in primary bile acids.

Quantitation of hepatitis C virus RNA in plasma and peripheral blood mononuclear cells of patients with chronic hepatitis treated with interferon-alpha.

We quantified hepatitis C virus (HCV) RNA at different times in plasma and peripheral blood mononuclear cells (PBMC) in 51 patients with chronic hepatitis C undergoing interferon-alpha2a (IFN-alpha2a) therapy. HCV RNA loads in plasma correlated with those in PBMC before and during the treatment (P<0.001). After treatment, a sustained response was observed in 19 patients (SR), a response followed by relapse in 9 (RR), and non response in 23 (NR). By univariate analysis PBMC HCV RNA load before treatment was lower in SR than in RR and NR (P = 0.003). In the 9 RR, HCV RNA disappeared in PBMC before or at the same time as in plasma and again became detectable in plasma and PBMC simultaneously or earlier in plasma. These results indicate that quantitation of HCV RNA in PBMC is not a useful parameter for the follow-up of treated patients.

[Do general practitioners want to manage chronic hepatitis C and take part in hepatitis C health networks? A national survey]. / Les médecins généralistes souhaitent-ils prendre en charge l'hépatite chronique virale C et participer aux réseaux ville-hôpital?

OBJECTIVES: To assess information that general practitioners had on hepatitis C and on the hepatitis C network in hospitals and private practice. METHODOLOGY: A national telephone survey of 604 general practitioners was conducted between March 18 and 23, 1998. RESULTS: Screening and management of hepatitis C was important for 89% and 97% of general practitioners. Screening was performed in relation to the relative risk (IV drug users 89%, blood transfusion before 1991 88%). General practitioners wanted more information on treatment (54%), patient counselling (42%) and the potential risks of the disease (42%). Of 604 general practitioners, 6% were involved in a hepatitis C network, while 21% were involved in another network (drug users 9%, AIDS 8%). Of the 94% general practitioners who were not part of the network, 33% were willing to join a hepatitis C network. Only 56% were aware of a hepatitis C network (press article 30%, mailing 17% or local meeting 12%). The difficulties for the involvement of general practitioners were: lack of time, topics not adapted to daily practice and geographic constraints (74%), too few patients in their practice (52%), no need (38%), the idea itself of a network and lack of information (28%). CONCLUSION: General practitioners screen patients at risk of hepatitis C. They want to be better informed about treatment, patient counselling, and the potential risks of hepatitis C. They are less involved in hepatitis C networks than in other networks (drug, AIDS). However, one third of general practitioners would like to be involved in a hepatitis C network. These results could be useful for implementing post-graduate courses and general practitioner training.

Tenoxicam, a non-steroid anti-inflammatory drug, is unable to increase the response rate in patients with chronic hepatitis C treated by alpha interferon.

The purpose of this study is to compare a combination of interferon (IFN)-alpha2a (Roferon) + Tenoxicam with IFN-alpha2a alone in the treatment of chronic hepatitis C. This prospective, randomized double-blind study included 149 patients, all of whom were diagnosed with active chronic hepatitis C but non-cirrhotic (ALT > or = 1.5 upper limit of normal, anti-hepatitis C virus (HCV) positive by enzyme-linked immunosorbant assay2 and RIBA3). The patients were randomized in two groups, as follows: G1 (n = 76): IFNalpha2a 3 million units times per week during 6 months + placebo; and G2 (n = 73): IFNalpha2a 3 million units three times per week + Tenoxicam (20 mg/day) during 6 months. Alanine aminotransferase (ALT) and HCV RNA were determined before and at months 6 and 12 of treatment. 2'5' oligoadenylate synthetase activity (2'5' AS) was dosed in mononuclear cells before and at 3-month treatment intervals in 28 patients. Liver biopsy was performed before and 6 months after the end of therapy. Parameters were similar before therapy for both groups. Biochemical and virological responses were similar for both groups at month 6 (49.3% vs. 42.9% and 43.3% vs. 38.3%, respectively) and month 12 (28.3% vs. 23.8% and 17.2% vs. 17.5%, respectively). HCV RNA level significantly decreased in both groups at month 6, with no difference whatever the therapy; however, the HCV RNA level returned to initial values at month 12 and was the only significant prognostic factor of a sustained response. No peak of 2'5' AS activity was observed during treatment in patients with dual therapy. A histological improvement was also noted in both groups without difference, regardless of therapy. The percentage of adverse events was identical for both groups. Paracetamol intake, assessed in 80 patients, was 49.1 g per 6 months in the G1 group and 22.5 g per 6 months in the G2 group (not significant). In conclusion, the non-steroid anti-inflammatory drug, Tenoxicam, does not increase IFNalpha efficacy in the treatment of chronic hepatitis C. This combination is well tolerated and partially lowers Paracetamol intake, but not preexisting alpha-IFN adverse events.

Anterior sacrodural attachments - Trolard's ligaments revisited.

In contrast to the attention paid to the structures surrounding spinal nerve roots in the intervertebral foramina, the anterior dural attachments are largely ignored, although they have been described since the last decades of the 19th century. These anterior attachments were systematically studied in a series of 30 cadaver dissections and were found to be present in almost 94% of cases. Four types of anterior attachments were observed. The most frequent form (84%) being a system of filaments that present as a double cross vault between the dura mater and the posterior longitudinal ligament extending from L3 to S3 levels. Less frequent were sagittal filaments (30%), short strong ligaments (17%) and a median septum from L3 to the end of the dural sac (7%). No attachments were found in two cadavers. Further studies are needed to clarify the possible role of these structures in transmitting movement to the dural sac and periradicular sleeves when mobilising the last three lumbar vertebrae or the sacrum.

Hepatitis C virus infection and allogeneic bone marrow transplantation.

Serum antibodies to hepatitis C virus (HCV) were tested for inpatients undergoing allogeneic BMT to determine the risk of acquiring HCV infection and the role of HCV in posttransplant liver complications. The HCV seroconversion rate was evaluated according to the date of BMT and blood donor screening at the time. Anti-HCV antibodies (anti-HCV) were detected with a second-generation ELISA and confirmed with a second-generation radioimmunoblot assay. All patients received leukocyte-depleted blood products and most received apheresis platelet concentrates. One hundred twenty of 181 consecutive patients transplanted from January 1987 to December 1991 were anti-HCV-negative before BMT, had at least 6 months of follow-up, and were thus evaluated for the seroconversion rate. Before screening for non-A, non-B hepatitis, 14% of the patients seroconverted to HCV (0.44% per unit transfused). After introduction of screening for alanine aminotransferase and antibodies to hepatitis B core antigen the risk of seroconversion was 4% per patient (0.26% per unit). When, in addition, blood was screened for anti-HCV the risk fell to 1.6% (0.03% per unit). Positive anti-HCV status before and after BMT was not predictive of veno-occlusive disease, liver graft-versus-host disease (GVHD), or death due to liver dysfunction. In contrast, the risk of chronic hepatitis was significantly increased.

[Reduction of the post-transfusion hepatitis C risk in patients undergoing bone marrow allograft]. / Diminution du risque d'hépatite C post-transfusionnelle chez les patients soumis à une allogreffe de moelle osseuse.

Post-transfusion hepatitis C incidence was studied in a series of patients with bone marrow allograft. The risk of HCV seroconversion was evaluated according to the date of grafting and the screening tests carried out in blood donors at this time. Anti-HCV antibodies were screened using Elisa tests of 2d generation and confirmed by Riba tests of 2d generation. Results were analysed. Out of 181 allografted patients from January 1987 to December 1991, 120 patients found anti-HCV negative prior to grafting, with at least six month post-transfusion follow-up were considered as evaluable in terms of HCV seroconversion. All these patients had received leucodepleted blood products and the most of them platelet unit concentrates. Prior to implementation of screening tests for non-A, non-B hepatitis, 14% of patients had seroconverted (0.44% per transfused product); after introduction of the screening for indirect markers (ALAT) and for antibodies directed against the antigen of hepatitis B virus core (anti-HBc), the seroconversion incidence was 4% (0.26% per product). At the present time, since the implementation of anti-HCV screening tests, the risk has reached 1.6% (0.03% per transfused product). 6 patients out of 7 having seroconverted have been developing chronic hepatitis.