PubMed Health⌕ Search

Biomedical subjects

D A Vuitton

Publications and source records attributed to D A Vuitton.

At least 19 recordsLinked to original sources

[Echinococcoses].

Human echinococcoses, cystic echinococcosis and alveolar echinococcosis are due to infections with the cestodes Echinococcus granulosus and E. multilocularis, respectively. Both zoonoses share a prolonged latency period before clinical presentation. However their evolution is fairly different: that of a begin tumor of the liver or lung for cystic echinoccocosis, and that of a slowly developing malignant tumor of the liver for alveolar echinoccocosis, with subsequent invasion of liver vessels and bile ducts and metastatic dissemination. Ultrasonography, CT-scan and specific serology are the key-exams for diagnosis. In both forms, surgery is the treatment of choice when a complete resection is possible. Liver transplantation may be an ultimate treatment option in very advanced cases of alveolar echinoccocosis. However, alternative treatment procedures have been proposed in the past 15 years and, combined with an earlier diagnosis, they have markedly improved patients survival and quality of life. Interventional radiology (puncture, aspiration, injection, reaspiration) has become a fully validated treatment of cystic echinoccocosis, and may be used in alveolar echinoccocosis for alleviating some of the complications of the disease such as biliary obstruction or bacterial superinfection. Albendazole, at high dosage, is a necessary complementary treatment after any intervention procedure, and for life when radical resection is not possible. Prevention relies on personal measures of hygiene and heating of contaminated food, and on collective measures aimed at reducing cestode egg shedding by the feces of infected canivores.

Abdominal Pain↗

Assessment of the epidemiological status of Echinococcus multilocularis in foxes in France using ELISA coprotests on fox faeces collected in the field.

The aim of this study was to estimate the relevance of Echinococcus multilocularis coproantigen detection in fox faeces collected in the field to identify different levels of endemicity for Echinococcus multilocularis on a large scale (n x 10 km(2)). Six study sites were selected in a high endemicity area and two study sites in a low endemicity area in eastern France on the basis of landscape composition. Sampling was undertaken in the winters of 1996-97, 1997-98 and 1998-99. At each site, (i) necropsy and intestine examination was undertaken on a sample of shot foxes (total number of foxes, 222), and (ii) fox faeces were collected in the field along road verges, and scored for degradation status (total number of faeces, 625). Fox faeces were also sampled in a control area (n=30) in western France in the summer of 1998. Intestines were examined according to the sedimentation method. Echinococcus multilocularis coproantigens were detected by using two ELISA tests: EM-ELISA and EmA9-ELISA. The necropsy prevalence in high and low endemicity areas was 63.3% and 19.4%, respectively, and the distribution of adult worms in the fox population was highly overdispersed (75.5% of the total biomass was harboured by 11.6% of foxes). Using the two ELISA tests, there was no difference in the detection of E. multilocularis coproantigens in field faeces, regardless of the degradation status. The medians of EM- and EmA9-ELISA OD values of field faeces in high endemicity area were significantly higher than in low endemicity area (P<0.001 for both ELISA). The distribution of EM-ELISA OD values in low endemicity area was significantly higher (P=0.002) than in the control area. Moreover, for the two ELISA, the observed ELISA OD value distributions in high endemicity area, low endemicity area and control area seemed representative of the distribution of adult worms in fox populations. These results indicate that E. multilocularis coproantigen detection in field faeces could serve for large-scale surveillance, as an alternative to necropsy.

Animals↗

Transglutaminase-mediated cross-linking is involved in the stabilization of extracellular matrix in human liver fibrosis.

BACKGROUND/AIMS: Lysyl oxidase-mediated cross-linking contributes to the stabilization of collagen in liver fibrosis. We have investigated transglutaminase-mediated cross-linking, to determine if it participates in the stabilization of extracellular matrix in human liver fibrosis. METHODS: Transglutaminase activity was assessed in vitro by incorporation of biotinylated amine into liver proteins. The product of the transglutaminase-catalyzed cross-linking reaction, Nepsilon(gamma-glutamyl)lysine, and the extracellular proteins cross-linked by it, were localized by immunohistochemistry in fibrotic livers. The cross-linked complexes were extracted from liver tissue, immunopurified and characterized by Western blot. RESULTS: Transglutaminase, detected by immunohistochemistry, Western blot and by enzymatic activity, was found in higher amounts in fibrotic than in normal liver. The Nepsilon(gamma-glutamyl)lysine cross-link, undetectable in normal liver, was present extracellularly in fibrotic liver, where it was co-distributed with osteonectin, mostly in inflammatory areas submitted to an intense remodeling. Cross-linking of osteonectin by transglutaminase was confirmed by Western blot. In parasitic fibrosis transglutaminase also originates from the parasite. CONCLUSIONS: Transglutaminase-mediated cross-linking occurs in liver extracellular matrix during the early, inflammatory, stage of liver fibrosis, whereas cross-linking by pyridinoline occurs mostly later in the fibrotic process. This could lead to the development of new anti-fibrotic treatments targeted to a specific stage of fibrosis.

Cross-Linking Reagents↗

[Myelodysplasias and systemic diseases. A non-fortuitous association].

PURPOSE: Myelodysplastic syndromes are clonal hematologic disorders, expanded from myeloid stem cells. A primitive immunologic disorder is discussed. This hypothesis could explain a non-casual association with systemic diseases. The aim of our study is to test this hypothesis. METHODS: We retrospectively investigated the data of 60 patients with myelodysplastic syndromes (group I) hospitalized in our unit from 1990 to 1999. The frequency of systemic disorders was screened and compared to controls (group II). Group II consisted of 120 patients matched for age and sex and hospitalized in the same hospital during the same period. RESULTS: Sixty patients were included (mean age: 83 years old). Myelodysplastic syndrome subtypes were refractory anemia with excessive blasts (52%), refractory anemia (43%) and sideroblastic anemia (5%). Fourteen cases of systemic manifestations were reported in group I (23%) and five in the controls (4%) (P < 0.0001). Systemic manifestations in group I included vasculitis in six cases (42%), polyarthritis in three cases (21%), systemic amyloidosis AA in two cases (14%), relapsing polychondritis in one case, pyoderma gangrenosum in one case and celiac disease associated with a systemic granulomatosis in one case. In the controls, vasculitis was present in four cases and polyarthritis in one. Median age at onset of myelodysplastic syndrome was not influenced by the association with systemic disorders which, in return, have not influenced the myelodysplastic syndromes' subtypes. Myelodysplastic syndromes succeeded to systemic manifestations in 71.4% of cases and could not be attributed to immunosuppressive therapy. CONCLUSIONS: The association of myelodysplastic syndromes with systemic manifestations seems not to be casual. It raises the hypothesis of a primitive immunological disorder in both diseases. Moreover, the description of two cases of systemic amyloidosis and one case of pyoderma gangrenosum might suggest an additional disorder of macrophages or granular cells.

Age of Onset↗

An epidemiological and ecological study of human alveolar echinococcosis transmission in south Gansu, China.

Human alveolar echinococcosis (AE) is usually a rare, highly pathogenic zoonotic disease, transmitted across the northern hemisphere between fox and rodent hosts. In China the first cases were described in 1965; however very few epidemiological studies have been undertaken since. Following identification in 1991 of a serious focus of human AE in south Gansu province, detailed village-based community and ecological studies were carried out between 1994 and 1997. Hepatic ultrasound mass screening with serological testing (five tests) identified 84/2482 new AE cases (3%). An overall prevalence of 4.1% (135/3331) was recorded for the area when previous cases were also included. Based on a seropositive result only, without an ultrasound scan indication, no additional AE cases were identified. Of the evolutive AE cases, 96% were seropositive in at least one test, while up 15-20% of individuals who exhibited hepatic calcified lesions and 12-15% exhibiting hepatic nodular lesions were seropositive for specific Em2 or Em18 antibodies. Village (n=31) human AE prevalence rates varied from 0 to 15.8%. Questionnaire analysis indicated that total number of dogs owned over a period was a risk factor (P<0.006), but not a history of red fox hunting (P>0.6). Rodent ecology studies revealed an association between density indices of voles (Microtus limnophilus) and village AE prevalence rates, on the one hand, and village landscape characterised by a ratio of scrub/grassland to total area above 50% (P<0.005). Long-term transmission of Echinococcus multilocularis and risk of zoonotic infection of south Gansu farmers may be related ultimately to a process of deforestation driven by agriculture. This in turn probably results in creation of optimal peri-domestic habitats for rodents that serve as intermediate host species (such as M. limnophilus) and subsequent development of a peri-domestic cycle involving dogs.

Adult↗

Resistance/susceptibility to Echinococcus multilocularis infection and cytokine profile in humans. I. Comparison of patients with progressive and abortive lesions.

To clarify the role of Th1- and Th2-type cytokines in the various outcomes of human alveolar echinococcosis (AE), the cytokine immune response of self-cured patients was studied and compared with those of progressive AE patients and healthy subjects. Self-cured patients were divided into two groups according to the following clinical features: subjects who had positive Echinococcus multilocularis serologies and hepatic calcifications typical of AE were classified as 'abortive AE' patients, and those who had positive E. multilocularis serologies but no hepatic lesions or calcifications detectable by ultrasonography were classified as 'positive serology' subjects. Secretions of IL-5, IL-10 and interferon-gamma, and expression of IL-5 mRNA were evaluated in peripheral blood mononuclear cells (PBMC) stimulated in vitro with the mitogen phytohaemagglutinin-C or specific E. multilocularis antigenic preparations. The cytokine profile of abortive AE patients was the opposite of that observed in progressive AE patients. An intermediate profile was observed in positive serology subjects. PBMC from abortive AE patients, whether non-stimulated or stimulated with PHA and antigenic preparations, secreted significantly lower levels of IL-10 than those isolated from progressive AE patients. Our observations seem to confirm the regulatory role of IL-10 in the immunopathology of human AE.

Animals↗

Resistance/susceptibility to Echinococcus multilocularis infection and cytokine profile in humans. II. Influence of the HLA B8, DR3, DQ2 haplotype.

Differences have been shown between HLA characteristics of patients with different courses of alveolar echinococcosis (AE). Notably the HLA B8, DR3, DQ2 haplotype was associated with more severe forms of this granulomatous parasitic disease. We compared IL-10, IL-5, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) secretion by peripheral blood mononuclear cells (PBMC) isolated from eight HLA-DR3+, DQ2+, B8+ AE patients and from 10 HLA-DR3-, DQ2-, B8- patients after non-specific mitogenic and specific Echinococcus multilocularis antigenic in vitro stimulation. PBMC from seven HLA-DR3+, DQ2+, B8+ healthy subjects and nine HLA-DR3-, DQ2-, B8- subjects were also studied as controls. PBMC from AE patients with HLA DR3+, DQ2+ haplotype secreted higher levels of IL-10 without any stimulation and after specific antigenic stimulation than did patients without this haplotype. Higher levels of IL-5 and IFN-gamma were also produced by these patients' PBMC after stimulation with non-purified parasitic antigenic preparations; however, the specific alkaline phosphatase antigen extracted from E. multilocularis induced only Th2-type cytokine secretion. A spontaneous secretion of TNF by HLA DR3+, DQ2+ B8+ AE patients was also found. These results suggest that HLA characteristics of the host can influence immune-mediated mechanisms, and thus the course of AE in humans; specific antigenic components of E. multilocularis could contribute to the preferential Th2-type cytokine production favoured by the genetic background of the host.

Animals↗

Epidemiology of alveolar echinococcosis in Xinjiang Uygur autonomous region, China: a preliminary analysis.

The Xinjiang Uygur autonomous region (XUAR) in north-western China is known to be endemic for Echinococcosis multilocularis, the causative agent of human alveolar echinococcosis (HAE). Despite regular reports of HAE cases in their region, very little is known about the local epidemiology of the disease or the transmission of E. multilocularis. The epidemiology of HAE in Xinjiang has now been investigated by the analysis of data collected from the medical records of 157 clinical cases who had attended the four main hospitals in the region. These data indicate that the disease is relatively common in the Altai, western Junggar, and Tianshan mountain ranges, whereas the Tarim and Junggar basins are likely to be of low endemicity. The prevalence of the disease in the Kunlun mountains is not clear. Semi-nomadic groups, especially those of Kazakh or Mongol origin, have a higher risk of infection than other ethnic groups. Prevalence of the disease in humans appears to be correlated with aspects of the local climate, such as annual precipitation and temperature. Red foxes, Microtinae, Ochotona spp. and Marmota spp. may be important hosts of E. multilocularis in the XUAR, sustaining the transmission cycles of the parasite.

Adolescent↗

A twenty-year history of alveolar echinococcosis: analysis of a series of 117 patients from eastern France.

OBJECTIVES: Alveolar echinococcosis of the liver is a very rare and severe parasitic disease due to the growth of the larva of Echinococcus multilocularis. The aim of this paper was to describe a 20-year study of the epidemiological, clinical and therapeutic aspects of alveolar echinococcosis in eastern France. DESIGN: One hundred and seventeen consecutive cases, diagnosed and followed in our liver unit, were studied from 1972 to 1993. METHODS: Data from 85 patients followed since 1983 (period B) were compared to data from a first series of 32 patients (period A) collected from 1972 to 1982; 1983 was chosen as the cut-off year because of the numerous changes that occurred in the diagnosis, follow-up and treatment of the disease at this time, in particular the introduction of parasitostatic benzimidazoles. RESULTS: The results of patient follow-up were evaluated in December 1997. The cumulative prevalence was 2.5 per 100,000 persons in period A whereas it reached 6.6 per 100,000 in period B. The annual incidence in period B was 7.3 on average, compared with 2.7 in period A. Twenty-nine per cent of patients from period B were asymptomatic at the time of diagnosis compared with 10% in period A. This change was correlated with less advanced liver lesions, and was related to the extensive use of abdominal ultrasound, and from 1987, serological screening. Curative resections were performed in 24% of the cases in period B versus only 3% in period A. From 1986, liver transplantations were performed in eight patients from period A and 13 patients from period B. In period B, palliative surgery was frequently replaced by radiological non-operative procedures to treat abscesses and jaundice. From 1982, 73 patients received benzimidazoles for a period of time ranging from 4 to 138 months. Stabilization of the lesions was observed in two-thirds of the patients. Episodes of jaundice or digestive haemorrhage due to portal hypertension were 31.5 and 11 times less frequent respectively in patients from period B compared with period A. Actuarial survival at 5 years improved from 67% in period A to 88% in period B in patients of similar age. CONCLUSIONS: Radical changes in the diagnosis and the management of alveolar echinococcosis have occurred during the last decade. Together they have contributed to an improvement in the status of the patients affected by this very severe parasitic disease.

Benzimidazoles↗

Immunodiagnosis of Echinococcus infections: confirmatory testing and species differentiation by a new commercial Western Blot.

The Echinococcus Western Blot IgG (LDBIO Diagnostics, Lyon, France), using a whole larval antigen from Echinococcus multilocularis, was evaluated for serodiagnosis and differentiation between two human parasitic infections of worldwide importance: cystic echinococcosis, due to Echinococcus granulosus, and alveolar echinococcosis, due to E. multilocularis. Fifty and 61 serum samples from patients with cystic and alveolar echinococcosis, respectively, were used for assessing diagnostic sensitivity. The sensitivity of the assay was compared with those of screening tests used for these applications. Sera used for assessing cross-reactivities were from 154 patients with other diseases, either parasitic or not. The assay allowed the detection of serum immunoglobulin G antibodies in 97% of Echinococcus-infected patients. It had a higher sensitivity than screening assays for the detection for each echinococcosis. The assay allowed us to correctly distinguish between E. granulosus- and E. multilocularis-infected patients in 76% of cases. It did not allow us to distinguish active from inactive forms of both echinococcoses. The occurrence of cross-reactivities with neurocysticercosis indicates the necessity for retesting sera with species-specific antigens, for rare patients with neurologic disorders. This study shows the usefulness of the commercially available Echinococcus Western Blot IgG for the serological confirmation of human echinococcosis.

Animals↗

Primary disease recurrence after liver transplantation for alveolar echinococcosis: long-term evaluation in 15 patients.

Between 1986 and 1991, 21 patients received liver grafts in our center for incurable alveolar echinococcosis (AE). The aim of this study was to analyze the long-term results in 15 of these 21 patients who survived more than 1 year after undergoing a liver transplantation (LT). The follow-up, mainly aimed at the diagnosis of recurrence, consisted of repeated radiological and specific immunological investigations. The role of pre- and post-LT benzimidazole (BZM) therapy was also evaluated. Among the 15 patients, 8 patients had a palliative LT related to previously known pulmonary AE metastases and/or inextirpable abdominal parasitic foci. In the 7 remaining patients, LT was considered curative. In June 1998, the mean follow-up duration was 96 months (range: 28-138 months). Five late deaths occurred, 2 of them were directly related to residual AE. A reinfection of the graft was observed in 4 patients. Preoperative BZM therapy seemed useful in preventing or delaying the parasitic recurrence. Post-LT BZM was able to stabilize and even to reduce residual AE. The anti-Em2 enzyme-linked immunosorbent assay (ELISA), which is the standard test used in patient follow-up after partial liver resection for AE, did not appear useful in detecting recurrence here; however, an ELISA, using a crude heterologous antigen (Echinococcus granulosus) allowed early diagnosis of residual AE. In conclusion, primary disease recurrence is not rare after LT for AE. Immunosuppressive therapy may favor larval growth in extrahepatic sites; therefore, an extensive extrahepatic radiological check-up has to be performed before LT. BZM therapy seems to stabilize residual foci. Anti-Eg immunoglobulin G (IgG) follow-up is the most useful test for early diagnosis of parasite recurrence.

Adult↗

[Psychoimmunology: a questionable model?].

INTRODUCTION: The concept of "psychoimmunology" that had long been supported by clinical observation and common sense, has acquired a sound scientific basis in the last two decades. The discovery of neuro-mediators and cytokines and their receptors shared by the central nervous system and the immune system has prompted research work using reliable methodologies to study the relationship between a 'hard' scientific field, such as immunology, and a 'soft' one, such as the behavioral sciences. CURRENT KNOWLEDGE AND KEY POINTS: The complexity of the studies on stress and immunity lies upon the choice of immunological measurements and the development of reproducible stress protocols. Models of stress in experimental animals may address acute versus chronic stress, and individual versus social stress. In humans, typical situations such as academic exams, and care given to patients with dementia, for instance, have been chosen to study large groups of subjects. The development of self-questionnaires for a reliable evaluation of stress and its consequences has led to more accurate measurements of psychosocial events. In animals, acute stress usually drives the immune response towards a Th2, grossly 'immunosuppressive,' profile. In humans, acute stress associates an endocrine response (characterized by glucocorticoid secretion and hyperprolectinemia) with an immunosuppression. Chronic stress is more likely to induce a range of effects, depending on the capacity of the subject to cope with stress, and on his/her social environment. Among the numerous mediators of the hypothalamo-pituitary cascade, Corticotropin Releasing Hormone is a key factor in the stress-immunity relationship. Several studies in humans have demonstrated the influence of stress on the susceptibility to infections (including HIV infection) and on survival in malignant diseases. In autoimmune diseases, a high prevalence of depression, as well as a particular sensitivity to stressful events, seem to modify the course of conditions such as systemic lupus erythematosus, rhumatoid arthritis or Sjögren's disease. The relationship between stress and diseases is based on the pathogenic model which involves the following chain of events: stressor, reaction to stress, neuro-endocrine changes, abnormalities of the immune response, and occurrence (or aggravation) of a disease. The evolution from health to disease could be associated, at least partially, with a 'passive' immunosuppressive mode of response, mediated by the pituitary-adrenal axis, typically the opposite of an 'active,' immunostimulant mode of response, mediated by adrenergic stimulation. FUTURE PROSPECTS AND PROJECTS: Concept-related problems still remain to be solved: adaptation to stress ('coping'), is both genetically and socially mediated; the significance and interpretation of stress-related abnormalities and their precise involvement in the pathogenesis of diseases may be ambiguous. However, available epidemiological and pathophysiological evidence is currently sufficient to allow physicians in their everyday practice to take stress and depression into account in order to markedly improve the prognosis of many diseases related to immune responses. Prospective studies of neuropsychological intervention, using either pharmacologic or behavioral approaches, should be made to provide the necessary rational to a psychoimmunological management of patients.

Adaptation, Psychological↗

[Treatment of recurrent ulceration with low doses of thalidomide. Pilot study in 17 patients].

PURPOSE: Though thalidomide in a dosage of 100 mg/day is the standard treatment for recurrent oral and genital ulcers (OGU), its toxicity would be less important with lower dosage, while its efficacy would be identical. Furthermore, duration of treatment might be a major risk factor for the development of subsequent polyneuropathy. To determine the dosage of thalidomide leading to the best efficacy/toxicity ratio, a pilot study was conducted from 1993 to 1996. METHODS: Seventeen patients with OGU (mean age: 43 years, sex-ratio: 12:5) were included in the study and presented either recurrent oral ulcerations (8 patients), oro-genital ulcerations (3 patients), Behçet disease (4 patients), or recurrent OGU associated with leukemia (2 patients). The initial dosage of thalidomide was 50 mg/day (1 tablet) for 1 month. If the patient's condition improved, the dosage was reduced to one tablet every other day for 1 month and one tablet every 3 days thereafter. Nerve conduction studies (EMG) were performed at inclusion in the study and every 6 months thereafter. RESULTS: Among the 17 patients, remission was observed in ten patients within the first month of treatment and the condition of seven patients improved. Complete remission was observed in six patients after a 2-month treatment and in one patient after 4 months. A 200-mg/8 days dosage induced prolonged remission in 12 patients. Among them, ten patients received a 150-mg dosage over 8 days thereafter and disease relapsed in four of them. Among the six patients who received a 100-mg dosage over 8 days, only one relapse was observed. EMG showed a decrease in sensory nerve action potentials in six patients after 8 months and a half on average. Only three patients had to discontinue their treatment due to the occurrence of either paresthesia (2 patients) or areflexia (1 patient). Our study shows that initially a 50-mg/day dose is efficacious in the treatment of OGU and that administration of one tablet every 2 or 3 days is efficacious in more than 60% of the patients to maintain remission. CONCLUSION: A dosage of 50 mg/day is initially efficacious in most cases, provided that the patient is carefully followed up to allow early detection of potential peripheral neuropathy.

Adult↗

Highly active antiretroviral therapy (HAART) for the treatment of infection with human immunodeficiency virus type 1.

Highly active antiretroviral therapy (HAART) refers to a broad category of treatment regimens usually comprised of three or more antiretroviral drugs that, in previously untreated HIV-1-infected patients, are expected to reduce plasma virus levels below the limits of detection. Most HAART regimens include drugs from at least two of the three classes of antiretroviral therapy (nucleoside analog reverse transcriptase (RT) inhibitors, non-nucleoside analog RT inhibitors, and protease inhibitors). In deciding when to initiate antiretroviral therapy, physicians and their patients must balance the virological and immunological benefits of early treatment with the costs of drug therapy, the risk of drug side effects, and the risk of drug resistance if adherence is suboptimal. In previously untreated patients, HIV-1 replication can be suppressed indefinitely with certain HAART regimens. In previously treated patients, the benefits of HAART are often significantly diminished.

Anti-HIV Agents↗