[Hepatitis C in a psychiatric setting: A forgotten reservoir?] / Hépatite C en milieu psychiatrique : un réservoir oublié ?

Hepatitis C is a transmissible hepatic and extra-hepatic disease caused by the hepatitis C virus (HCV). HCV develops into a chronic infection among approximately 70% of the contaminated subjects. Chronic HCV infection is estimated to affect between 0.5% and 1 % of the general population in France, which causes an important burden of disease, in particular due to the occurrence of cirrhosis and liver cancer. New antiviral drugs now allow to cure more than 95% of patients in just a few weeks of treatment with very limited safety issues. This therapeutic revolution has led the World Health Organization and many national governments to aim for an elimination of HCV, which has been defined as a 90%-reduction of the incidence rate, and a 65%-reduction in the number of HCV-related deaths on the basis of the 2015 figures. In this respect, the French Ministry of Health has recently decided to extend the ability to prescribe the new antiviral drugs to any physician. However, the elimination campaign of HCV will also need to correctly identify, screen, and treat the main target populations. If people who inject drugs (PWIDs) certainly constitute the most important population concerned by the challenge of HCV elimination, more hidden reservoirs in which HCV transmission can insidiously evolve should be identified and specifically targeted as well. Inpatient psychiatric populations might constitute one of these hidden reservoirs. International data suggest that chronic HCV infection affects approximately 5% of psychiatric inpatients in Europe. This very high prevalence estimate can in part be due to the very frequent psychiatric disorders found among the current or former PWIDs. However, a part of the seropositive patients does not report a history of drug use, and other factors could contribute to the increased risk of contamination in this population including atypical routes of transmission related to institutional promiscuity. Exploring the general profile and risk-behaviors of the psychiatric inpatients found infected by the HCV is thus warranted for future studies. Screening and treating HCV in the specific population of psychiatric patients is part of the general public health objective of eliminating HCV at a national level. Moreover, it also directly fits into the individualized psychiatric care. Many recent data suggest that HCV also has a neural tropism, in particular within glial cells, such as astrocytes or oligodendrocytes. As such, HCV foments inflammatory processes in the brain and contributes to cognitive impairments and psychiatric symptoms such as anxiety or depression. At the individual level, treating HCV infection can improve the psychiatric state and increase patients' outcomes in terms of well-being and quality of life. For all these reasons, the field of psychiatry needs local and national actions for informing and training professionals about HCV screening and treating modalities. Patient and family associations also need to be involved in this general effort of micro-elimination. A key role should be assigned to the general practitioners embedded within inpatient psychiatric units. They are the best fitted professionals to screen, treat, and empower patients, to inform and train other caregivers of the psychiatric field, and to act as a relay with hepatology teams if required. Hospital pharmacists are other important stakeholders. In a national context in which the funding of psychiatric care, including medications, is based on predefined funding envelops, innovative initiatives will have to be set up by local or national health authorities, in partnership with pharmacists, to allow for the treatment of psychiatric inpatients. In conclusion, the world of psychiatry is a possible hidden reservoir of HCV and, as such, a part of the challenge for eliminating the virus. Patients, families, and caregivers will have to be correctly sensitized and trained to play their role in the process. Specific investigations will be required to better understand why such an increased prevalence of HCV is observed in this population. Specific adaptations of the cascade of care within psychiatric settings, including access to treatment, will need to be designed, implemented, and evaluated for reaching micro-elimination of HCV in psychiatry.

Daily cannabis and reduced risk of steatosis in human immunodeficiency virus and hepatitis C virus-co-infected patients (ANRS CO13-HEPAVIH).

Liver steatosis is common in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-co-infected patients. Some recent studies have found that cannabis use is negatively associated with insulin resistance in the general population and in HIV-HCV-co-infected patients. Given the causal link between insulin resistance and steatosis, we hypothesized that cannabis use has a positive impact on steatosis. Therefore, we aimed to study whether cannabis use in this population was associated with a reduced risk of steatosis, measured by ultrasound examination. ANRS CO13-HEPAVIH is a French nationwide multicentre cohort of HIV-HCV-co-infected patients. Medical and socio-behavioural data from clinical follow-up visits and annual self-administered questionnaires were prospectively collected. A cross-sectional analysis was conducted using data from the first visit where both ultrasound examination data for steatosis (positive or negative diagnosis) and data on cannabis use were available. A logistic regression model was used to evaluate the association between cannabis use and steatosis. Among study sample patients (n = 838), 40.1% had steatosis. Fourteen per cent reported daily cannabis use, 11.7% regular use and 74.7% no use or occasional use ("never or sometimes"). Daily cannabis use was independently associated with a reduced prevalence of steatosis (adjusted odds ratio [95% CI] = 0.64 [0.42;0.99]; P = .046), after adjusting for body mass index, hazardous alcohol consumption and current or lifetime use of lamivudine/zidovudine. Daily cannabis use may be a protective factor against steatosis in HIV-HCV-co-infected patients. These findings confirm the need for a clinical evaluation of cannabis-based pharmacotherapies in this population. Eudract.ema.europa.eu number, DGS050367.

Benefits of task-shifting HIV care to nurses in terms of health-related quality of life in patients initiating antiretroviral therapy in rural district hospitals in Cameroon [Stratall Agence Nationale de Recherche sur le SIDA (ANRS) 12110/Ensemble pour une Solidarité Thérapeutique Hospitalière en Réseau (ESTHER) substudy].

OBJECTIVES: The World Health Organization (WHO) recommends task-shifting HIV care to nurses in low-resource settings with limited numbers of physicians. However, the effect of such task-shifting on the health-related quality of life (HRQL) of people living with HIV (PLHIV) has seldom been evaluated. We aimed to investigate the effect of task-shifting HIV care to nurses on HRQL outcomes in PLHIV initiating antiretroviral therapy (ART) in rural district hospitals in Cameroon. METHODS: Outcomes in PLHIV were longitudinally collected in the 2006-2010 Stratall trial. PLHIV were followed up for 24 months by nurses and/or physicians. Six HRQL dimensions were assessed during face-to-face interviews using the WHO Quality of Life (WHOQOL)-HIV BREF scale: physical health; psychological health; independence level; social relationships; environment; and spirituality/religion/personal beliefs. The degree of task-shifting was estimated using a consultant ratio (i.e. the ratio of nurse-led to physician-led visits). The effect of task-shifting and other potential correlates on HRQL dimensions was explored using a Heckman two-stage approach based on linear mixed models to adjust for the potential bias caused by missing data in the outcomes. RESULTS: Of 1424 visits in 440 PLHIV (70.5% female; median age 36 years; median CD4 count 188 cells/µL at enrolment), 423 (29.7%) were task-shifted to nurses. After multiple adjustment, task-shifting was associated with higher HRQL level for four dimensions: physical health [coefficient 0.7; 95% confidence interval (CI) 0.1-1.2; P = 0.01], psychological health (coefficient 0.5; 95% CI 0.0-1.0; P = 0.05), independence level (coefficient 0.6; 95% CI 0.1-1.1; P = 0.01) and environment (coefficient 0.6; 95% CI 0.1-1.0; P = 0.02). CONCLUSIONS: Task-shifting HIV care to nurses benefits the HRQL of PLHIV. Together with the previously demonstrated comparable clinical effectiveness of physician-based and nurse-based models of HIV care, our results support the WHO recommendation for task-shifting.

Factors associated with guideline-based hepatitis C virus (HCV) treatment initiation in HIV/HCV-coinfected patients: role of comorbidities and physicians' perceptions.

OBJECTIVES: Many HIV-infected patients with chronic hepatitis C virus (HCV) infection do not receive treatment for HCV infection, often because of contraindications or poor adherence to anti-HIV therapy. The aim of this study was to identify factors influencing guideline-based HCV treatment initiation in a large cohort of HIV/HCV-coinfected patients. METHODS: Between 2005 and 2011, 194 (40.5%) of 479 coinfected patients not previously treated for HCV infection started this treatment based on current recommendations, i.e. a Metavir score >F1 for liver fibrosis; HCV genotype 2 or 3 infection; or HCV genotype 1 or 4 infection and low HCV viral load (<800000 IU/mL), whatever the fibrosis score. Clinical and biological data were compared between patients who started HCV therapy during follow-up and those who did not. RESULTS: In multivariate analyses, good adherence to treatment for HIV infection, as judged by the patient's physician, was associated with HCV treatment initiation [odds ratio (OR) 2.37; 95% confidence interval (CI) 1.17-4.81; P=0.017], whereas patients with children (OR 0.53; 95% CI 0.30-0.91; P=0.022) and those with cardiovascular disease or respiratory distress (OR 0.10; 95% CI 0.01-0.78; P=0.03) were less likely to be treated. CONCLUSIONS: Adherence to treatment for HIV infection, as judged by the patient's physician, appears to have a major influence on the decision to begin treatment for HCV infection in coinfected patients. This calls for specific therapeutic education and adherence support in order to ensure timely anti-HCV therapy in this population.

Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii.

BACKGROUND: Obesity is associated with increased health risk and has been associated with alterations in bacterial gut microbiota, with mainly a reduction in Bacteroidetes, but few data exist at the genus and species level. It has been reported that the Lactobacillus and Bifidobacterium genus representatives may have a critical role in weight regulation as an anti-obesity effect in experimental models and humans, or as a growth-promoter effect in agriculture depending on the strains. OBJECTIVES AND METHODS: To confirm reported gut alterations and test whether Lactobacillus or Bifidobacterium species found in the human gut are associated with obesity or lean status, we analyzed the stools of 68 obese and 47 controls targeting Firmicutes, Bacteroidetes, Methanobrevibacter smithii, Lactococcus lactis, Bifidobacterium animalis and seven species of Lactobacillus by quantitative PCR (qPCR) and culture on a Lactobacillus-selective medium. FINDINGS: In qPCR, B. animalis (odds ratio (OR)=0.63; 95% confidence interval (CI) 0.39-1.01; P=0.056) and M. smithii (OR=0.76; 95% CI 0.59-0.97; P=0.03) were associated with normal weight whereas Lactobacillus reuteri (OR=1.79; 95% CI 1.03-3.10; P=0.04) was associated with obesity. CONCLUSION: The gut microbiota associated with human obesity is depleted in M. smithii. Some Bifidobacterium or Lactobacillus species were associated with normal weight (B. animalis) while others (L. reuteri) were associated with obesity. Therefore, gut microbiota composition at the species level is related to body weight and obesity, which might be of relevance for further studies and the management of obesity. These results must be considered cautiously because it is the first study to date that links specific species of Lactobacillus with obesity in humans.

Impact of HAART exposure and associated lipodystrophy on advanced liver fibrosis in HIV/HCV-coinfected patients.

The impact of antiretroviral drug exposure and associated lipodystrophy and/or insulin resistance (IR) on advanced liver fibrosis in HIV/HCV-coinfected patients is not fully documented. We determined the prevalence of advanced liver fibrosis (defined by hepatic stiffness ≥9.5 kPa) and associated factors, focusing on the impact of highly active antiretroviral therapy and its major adverse effects (lipodystrophy and IR), in 671 HIV/HCV-coinfected patients included in the ANRS CO13 HEPAVIH cohort. One hundred ninety patients (28.3%) had advanced liver fibrosis. In univariate analysis, advanced liver fibrosis was significantly associated with male sex, higher body mass index, HCV infection through intravenous drug use, a lower absolute CD4 cell count, a longer history of antiretroviral treatment, longer durations of protease inhibitors, non-nucleoside reverse transcriptase inhibitors and NRTI exposure, lipodystrophy, diabetes, and a high homeostasis model assessment method (HOMA) value. The only antiretroviral drugs associated with advanced liver fibrosis were efavirenz, stavudine and didanosine. In multivariate analysis, male sex (OR 2.0, 95% CI 1.1-3.5; P = 0.018), HCV infection through intravenous drug use (OR 2.0, 95% CI 1.1-3.6; P = 0.018), lipodystrophy (OR 2.0, 95% CI 1.2-3.3; P = 0.01), median didanosine exposure longer than 5 months (OR 1.7, 95% CI 1.0-2.8; P = 0.04) and a high HOMA value (OR 1.1, 95% CI 1.0-1.2; P = 0.005) remained significantly associated with advanced liver fibrosis. Mitochondrial toxicity and IR thus appear to play a key role in liver damage associated with HIV/HCV-coinfection, and this should be taken into account when selecting and optimizing antiretroviral therapy. Antiretroviral drugs with strong mitochondrial toxicity (e.g. didanosine) or a major effect on glucose metabolism should be avoided.

Gastric cancer surveillance in a high-risk population in tuscany (Central Italy): preliminary results.

BACKGROUND/AIMS: The surveillance of subjects at high risk for developing gastric cancer (GC) may represent an effective strategy for reducing specific morbidity and mortality. The aim of this study was to identify GC at its initial phase and to identify precancerous lesions in a group of GC high-risk subjects. METHODS: We enrolled first-degree relatives of patients affected by GC who resided in a GC high-risk area (Tuscany, Central Italy). The study's protocol included the collection of several individual measurements, including a blood sample for the determination of specific biomarkers, an upper digestive tract endoscopy with detailed gastric biopsies and Helicobacter pylori (Hp) treatment followed by a specific check. RESULTS: We enrolled 167 subjects who were members of 128 different familial groups with GC history. We identified 1 case of initial-phase GC, 1 gastric dysplasia type II, 32 intestinal metaplasia, 10 gastric atrophy, and 21 atrophic chronic gastritis. 81 subjects were Hp-positive and underwent eradication therapy. CONCLUSION: This study of a GC high-risk Italian population reveals positive results in terms of population compliance, the identification of specific gastric lesions requiring close follow-up and successful therapy for Hp infection. To define future surveillance strategies, a longer follow-up of these patients is necessary.

Myoxinol ointment for the treatment of acute fissure.

Myoxinol is a complex of oligopeptides obtained from the seeds of Hibiscus esculentus used in cosmetic as natural alternative to botulin toxin. The aim of the study was to evaluate the safety and effectiveness of local myoxinol for the treatment of acute anal fissure. All the consecutive patients with acute fissure treated from January to June 2014 underwent 30 days of topical treatment (twice/day) with a mioxinol based ointment. Pain, symptomatic relief, fissure healing and re-epithelization, 1-year recurrence rate, subjective satisfaction and need for further treatments were evaluated. During the study period 157 patients were eligible for data analysis (91 males: 58%; mean age 38 years: range 17-83). Median anal pain score was 7.1 pre-treatment and 1.7 and 0.9 after 30 days and 12 months from treatment, respectively (p: 0.0001). After the treatment period complete healing was achieved in 103 patients (65.5%), relevant improvement in 31 (20%) and no improvement in 21 patients (13.5%). Overall efficacy rate was 85.5%. A significant difference was reported considering patients with pre-treatment VAS between 1-5 and 6-10 (p: 0.004). Twenty-nine patients (18.5%) required further treatments. Hydrolyzed Hibiscus esculentus extract was proven to be an effective and well-tolerated topical treatment for acute fissure, with a high healing rate, a significant reduction of pain and a low 1-year recurrence rate.

The negative impact of HBV/HCV coinfection on cirrhosis and its consequences.

BACKGROUND: Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series. AIM: To compare the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study. PATIENTS AND METHODS: Of the 20 936 included patients, 95 had HBV/HCV coinfection (hepatitis B surface antigen, anti-HCV antibody and HCV RNA positive) and were matched with 375 HBV- and 380 HCV-monoinfected patients on age, gender and time since HBV or HCV diagnosis. RESULTS: F3-F4 fibrosis was more frequent in coinfected patients (58%) than in HBV- (32%, P < .0001), but similar in HCV-monoinfected patients (52%, P = .3142). Decompensated cirrhosis was more frequent in coinfected patients (11%) than in HBV- (2%, P = .0002) or HCV- (4%, P = .0275) monoinfected patients. Past excessive alcohol use was more frequent in coinfected patients (26%) than in HBV (12%, P = .0011), but similar in HCV monoinfected patients (32%, P = .2868). Coinfected patients had a higher proportion with arterial hypertension (42%) than HBV- (26%) or HCV-monoinfected patients (25%) (P < .003). Multivariable analysis confirmed the association between F3-F4 fibrosis and HCV infection in HBV-infected patients (OR = 3.84, 95% CI 1.99-7.43) and the association between decompensated cirrhosis and coinfection in HBV infected (OR = 5.58, 95% CI 1.42-22.0) or HCV infected patients (OR = 3.02, 95% CI 1.22-7.44). CONCLUSIONS: HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV-monoinfected patients. HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients.

[New tools for preventing and evaluating risk practices for hepatitis C transmission among injection drug users: some reflections on injection rooms and the measurement of risk-taking behaviors]. / Quels nouveaux outils pour prévenir et évaluer les pratiques à risque chez les injecteurs de drogue face au VHC? Réflexions sur les salles d'injection et les outils de mesure des prises de risques.

Injection rooms should be able to contribute to the prevention of the risks of transmission of hepatitis C (HCV) among intravenous drug users (IDUs). However, these services have yet to be set up and tested in France. This article presents a literature review of injection rooms and explores possible ways of evaluating the effects of this type of service on risks for HCV. Given the difficulties of estimating the service's impact on the incidence of HCV, evaluations could target injection-related risk taking behaviors. The second part of the article addresses the issue of risk taking practices and presents a new research tool able to explore out-of-the-ordinary situations involving risk-taking. Tested on a population of IDUs in Marseille, this tool detects forms of risk-taking and contexts in which injection is performed, which are always missed by the usual measures of risk practices. It could therefore be added to these measures and be useful for evaluating injection rooms.

Tropheryma whipplei DNA in bronchoalveolar lavage samples: a case control study.

Tropheryma whipplei, the causative bacterium of Whipple's disease, can cause acute pneumonia. We performed a case-control study including patients with T. whipplei in bronchoalveolar lavages (BALs) and controls in order to compare patients' clinical statuses. We tested T. whipplei PCR from January 2013 to December 2014, in all the 1438 BALs in Marseille, France. Controls were hospitalized in the same unit during the same period and were comparable in age and sex. Eighty-eight BALs (6.1%) were positive for T. whipplei and 58 patients had pneumonia. Sixty-four patients were male with a mean age of 50.5 years. T. whipplei was commonly associated with aspiration pneumonia (18/88 patients compared with 6/88 controls, p 0.01) and was detected as a unique pathogen in nine cases. Overall, no difference was observed regarding immunocompromised status. Nevertheless, the six AIDS-infected patients in the T. whipplei group had a significantly lower CD4 level than the five AIDS-infected patients in the control group (49 vs. 320/mm3, p 0.01); in addition, five patients were treated with tumour necrosis factor alpha inhibitors (including three treated by monocolonal antibodies and two with soluble receptor) compared with none of the controls (p 0.03). Pneumocystis jirovecii was frequently associated with the T. whipplei group (7/88 vs. 0/88 in control group), Pseudomonas aeruginosa was only detected in the control group (8/88). This study adds evidence for a causative role of T. whipplei in pneumonia. In the future, an experimental model of pneumonia induced by T. whipplei will prove its role in pneumonia.

Failure to maintain long-term adherence to highly active antiretroviral therapy: the role of lipodystrophy.

In a sample of 277 patients included in the French APROCO cohort study who were initially adherent at follow-up visit 4 months after initiation of a protease inhibitor-containing regimen, 76.4% self-reported at least one lipodystrophy-related symptom and 30.0% failed to maintain adherence behaviour 20 months after enrolment. After multiple adjustment for other related factors, such as younger age, alcohol consumption and poor housing conditions, the number of self-reported lipodystrophy symptoms was independently associated with adherence failure.

Cancer risk among men with, or at risk of, HIV infection in southern Europe.

OBJECTIVE: To evaluate the cancer risk in southern European men with, or at risk of, HIV infection. DESIGN: An analysis of longitudinal data to assess time-dependent rare events. METHODS: Data from a cohort of HIV seroconverters, and from two hospital-based HIV seroprevalent cohorts were combined and analysed. The number of cancer cases observed was compared with the expected number, obtained from cancer incidence rates among men in the general population. Age-standardized incidence ratios (SIR) and their 95% confidence intervals (CI) were computed. RESULTS: A total of 19,609 person-years of observation were accumulated among HIV-positive men, and 7957 person-years among HIV-negative men. Among HIV-positive men, statistically significant increased SIR were seen for Hodgkin's disease (HD) (SIR = 8.7), liver cancer (SIR = 11.0), and cancer of the salivary glands (SIR = 33.6). An excess of lung cancer was seen among intravenous drug users (IDU), but not among homosexual men. When the risk of all non-AIDS-defining cancers was considered, HIV-positive men had a nearly twofold excess (95% CI: 1.2-2.8). A risk of similar magnitude emerged among HIV-negative IDU (95% CI: 1.0-4.5), largely attributable to lung cancer and HD. CONCLUSION: These findings confirm that HIV infection increases the risk of HD, whereas they suggest that the risk of hepatocellular carcinoma may also be enhanced by HIV infection. The observation of an elevated risk of lung cancer in both HIV-positive and HIV-negative IDU points to personal behaviours unrelated to HIV infection.

Amitriptyline in the treatment of headache in patients with Parkinson's disease: a double-blind placebo-controlled study.

We evaluated the effect of 25 mg bid amitriptyline on muscle contraction headache in 36 patients with Parkinson's disease in a randomized double-blind placebo-controlled study. Treatment lasted 12 weeks, and we assessed the efficacy by number of days with headache, sum-of-severity score (intensity X number of days with headache), and consumption of analgesics. We also administered Hoehn-Yahr staging, the Webster Rating Scale, the Mini-Mental State, and the Zung Self-Rating Depression Scale. We assessed the patients after a 4-week run-in period and after 4, 8, and 12 weeks of treatment. Thirty-one patients (15 in the amitriptyline group and 16 in the placebo group) completed the trial. Amitriptyline reduced the intensity and the frequency of headache, whereas the placebo did not. The Zung Depression Scale and the Webster Rating Scale findings remained unchanged.

Effect of indinavir and higher CD4+ T-cell count on viral load response after 6 months of highly active antiretroviral therapy.

This retrospective, unmasked chart review was undertaken to determine which HIV-infected patients receiving protease inhibitors (PIs) for the first time were most likely to experience a decrease in plasma viral load (PVL) and which factors were associated with a PVL < 500 copies/mL below the detectable limits after 6 months. A total of 308 patients aged > 15 years with a PVL > 500 copies/mL received therapy that included a PI in addition to other antiretroviral therapies (128 patients, saquinavir hard-gel capsule 600 mg TID; 107 patients, indinavir 800 mg TID; and 73 patients, ritonavir 600 mg BID). The choice of drug was at individual clinicians' discretion. Patients were followed for a median of 10 (range, 6 to 21) months. Of the 128 patients who received saquinavir, 45% were switched to another PI (33%, indinavir; 12%, ritonavir). Seventy percent of the 73 patients initially given ritonavir were switched (45%, indinavir; 25%, saquinavir), as were 23% of the 107 patients initially given indinavir (15%, saquinavir; 8%, ritonavir). A total of 34.1% (n = 105) of patients achieved a PVL < 500 copies/mL; in 51.6%, PVL decreased > 0.5 log copies/mL. In this subgroup, both treatment-naive patients and those who were receiving a new combination of antiretroviral therapy when they started PI treatment had a more pronounced decline in PVL (P < 0.001). After adjustment by logistic regression analysis for age, sex, mode of transmission, and duration of highly active antiretroviral therapy (HAART), CD4+ cell count and initial type of PI received were independently associated with PVL < 500 copies/mL. In the present study, the treatment success rate was low (34.1%) compared with rates observed in randomized, controlled trials. A higher CD4+ cell count and use of indinavir at the initiation of HAART are associated with a better viral load response.

Cerebrospinal fluid cytokines in AIDS dementia complex.

We evaluated cerebrospinal fluid (CSF) and serum concentrations of interleukin-1-alpha (IL-1-alpha), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in 30 patients with AIDS dementia complex (ADC), and in 20 HIV-seronegative subjects with other neurological diseases (OND). CSF TNF-alpha, IL-1-alpha and IL-6 were more frequently detectable in ADC patients than in OND subjects. These cytokines were also detectable in CSF of ADC patients with minimal symptoms. In contrast, the majority of both ADC and OND patients did not contain detectable serum levels of cytokines. Our data support the notion of intrathecal synthesis of cytokines in ADC patients and raise the possibility that activated macrophages may play a significant role in the pathogenesis of ADC.

Antithrombotic effect of indobufen in an experimental model of arterio-arterial microanastomosis in the rat.

Using an end-to-side microanastomosis of the left common carotid into the right common carotid of rats, implementing a potentially thrombogenic situation, we have investigated the possible antithrombotic effect of indobufen, a new antiplatelet drug. In eight of 15 untreated rats the anastomosis was totally obstructed by a single thrombus growing from the anastomotic wall. Indobufen treatment prevented thrombus formation completely in 14 of 15 rats (p less than 0.02). In treated animals indobufen also produced a statistically significant reduction of ADP-induced platelet aggregation relative to basal values. Platelet count were not influenced by drug treatment. Our experimental results suggest the potential usefulness of indobufen as an antithrombotic agent.