Management of hepatitis C virus (HCV) infection in drug substitution programs.

BACKGROUND: In Switzerland, intravenous drug use (IDU) accounts for 80% of newly acquired hepatitis C virus (HCV) infections. Early HCV treatment has the potential to interrupt the transmission chain and reduce morbidity/mortality due to decompensated liver cirrhosis and hepatocellular carcinoma. Nevertheless, patients in drug substitution programs are often insufficiently screened and treated. OBJECTIVE/METHODS: With the aim to improve HCV management in IDUs, we conducted a cross sectional chart review in three opioid substitution programs in St. Gallen (125 methadone and 71 heroin recipients). Results were compared with another heroin substitution program in Bern (202 patients) and SCCS/SHCS data. RESULTS: Among the methadone/heroin recipients in St. Gallen, diagnostic workup of HCV was better than expected: HCV/HIV-status was unknown in only 1% (2/196), HCV RNA was not performed in 9% (13/146) of anti-HCV-positives and the genotype missing in 15% (12/78) of HCV RNA-positives. In those without spontaneous clearance (two thirds), HCV treatment uptake was 23% (21/91) (HIV-: 29% (20/68), HIV+: 4% (1/23)), which was lower than in methadone/heroin recipients and particularly non-IDUs within the SCCS/SHCS, but higher than in the, mainly psychiatrically focussed, heroin substitution program in Bern (8%). Sustained virological response (SVR) rates were comparable in all settings (overall: 50%, genotype 1: 35-40%, genotype 3: two thirds). In St. Gallen, the median delay from the estimated date of infection (IDU start) to first diagnosis was 10 years and to treatment was another 7.5 years. CONCLUSIONS: Future efforts need to focus on earlier HCV diagnosis and improvement of treatment uptake among patients in drug substitution programs, particularly if patients are HIV-co-infected. New potent drugs might facilitate the decision to initiate treatment.

Helicopter rescue operations involving winching of an emergency physician.

OBJECTIVE: We sought to study the epidemiologic and medical aspects of alpine helicopter rescue operations involving the winching of an emergency physician to the victim. METHODS: We retrospectively reviewed the medical and operational reports of a single helicopter-based emergency medical service. Data from 1 January 2003 to 31 December 2008 were analysed. RESULTS: A total of 921 patients were identified, with a male:female ratio of 2:1. There were 56 (6%) patients aged 15 or under. The median time from emergency call to helicopter take-off was 7 min (IQR = 5-10 min). 840 (91%) patients suffered from trauma-related injuries, with falls from heights during sports activities the most frequent event. The most common injuries involved the legs (246 or 27%), head (175 or 19%), upper limbs (117 or 13%), spine (108 or 12%), and femur (66 or 7%). Only 81 (9%) victims suffered from a medical emergency, but these cases were, when compared to the trauma victims, significantly more severe according to the NACA index (p<0.001). Overall, 246 (27%) patients had a severe injury or illness, namely, a potential or overt vital threat (NACA score between 4 and 6). A total of 478 (52%) patients required administration of major analgesics: fentanyl (443 patients or 48%), ketamine (42 patients or 5%) or morphine (7 patients or 1%). The mean dose of fentanyl was 188 micrograms (range 25-750, SD 127). Major medical interventions such as administration of vasoactive drugs, intravenous perfusions of more than 1000 ml of fluids, ventilation or intubation were performed on 39 (4%) patients. CONCLUSIONS: The severity of the patients' injuries or illnesses along with the high proportion of medical procedures performed directly on-site validates emergency physician winching for advanced life support procedures and analgesia.

Mechanisms of successful amoxicillin prophylaxis of experimental endocarditis due to Streptococcus intermedius.

Prophylaxis with amoxicillin (40 mg/kg) was studied in rats with aortic valve vegetations. Bacteria on the valves were quantitated early (10 min to 6 hr) and late (three days) after intravenous challenge with tolerant Streptococcus intermedius. Amoxicillin reduced by 40% the number of bacteria per valve 10 min after intravenous challenge with 10(5) S. intermedius (P less than .05) and by 74% the incidence of endocarditis three days thereafter (P less than .0001). Bacterial multiplication started 2 hr after challenge in control rats, whereas bacteria disappeared in 6 hr in amoxicillin-treated rats. Intravenous penicillinase 30 min after challenge abolished successful amoxicillin prophylaxis, a result demonstrating the necessity of prolonged growth inhibition for protection. Growth inhibition for 18 hr (two subsequent amoxicillin doses) was necessary for protection after intravenous challenge with 10(5) S. intermedius. Thus, in the absence of bacterial killing, inhibition of valvular colonization by amoxicillin was not as important a mechanism of endocarditis prophylaxis as was prolonged inhibition of bacterial growth, which allowed adherent bacteria to be cleared from the valves.

Complementary effects of adenosine and angiotensin II in hypoxemia-induced renal dysfunction in the rabbit.

The acute renal effects of hypoxemia and the ability of the co-administration of an angiotensin converting enzyme inhibitor (perindoprilat) and an adenosine receptor antagonist (theophylline) to prevent these effects were assessed in anesthetized and mechanically-ventilated rabbits. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by the clearances of para-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In 8 untreated rabbits, hypoxemia induced a significant drop in mean blood pressure (-12 +/- 2%), GFR (-16 +/- 3%) and RBF (-12 +/- 3%) with a concomitant increase in renal vascular resistance (RVR) (+ 18 +/- 5%), without changes in filtration fraction (FF) (-4 +/- 2%). These results suggest the occurrence of both pre- and postglomerular vasoconstriction during the hypoxemic stress. In 7 rabbits pretreated with intravenous perindoprilat (20 microg/kg), the hypoxemia-induced changes in RBF and RVR were prevented. FF decreased significantly (-18 +/- 2%), while the drop in GFR was partially blunted. These results could be explained by the inhibition of the angiotensin-mediated efferent vasoconstriction by perindoprilat. In 7 additional rabbits, co-administration of perindoprilat and theophylline (1 mg/kg) completely prevented the hypoxemia-induced changes in RBF (+ 11 +/- 3%) and GFR (+ 2 +/- 3%), while RVR decreased significantly (-14 +/- 3%). Since adenosine and angiotensin II were both shown to participate, at least in part, in the renal changes induced by hypoxemia, the beneficial effects of perindoprilat and theophylline in this model could be mediated by complementary actions of angiotensin II and adenosine on the renal vasculature.

Two Cases of Interferon-Alpha-Induced Sarcoidosis Koebnerized along Venous Drainage Lines: New Pathogenic Insights and Review of the Literature of Interferon-Induced Sarcoidosis.

Sarcoidosis is a systemic granulomatous disorder of unknown origin commonly affecting the lung, the lymphoid system and the skin. We report here two cases of cutaneous sarcoidosis in two former intravenous drug users following interferon (IFN)-α and ribavirin therapy for chronic hepatitis C. Both patients developed skin sarcoidosis along venous drainage lines of both forearms, coinciding with the areas of prior drug injections. The unique distribution of the skin lesions suggests that tissue damage induced by repeated percutaneous drug injections represents a trigger for the local skin manifestation of sarcoidosis. Interestingly, skin damage was recently found to induce the local expression IFN-α, a well-known trigger of sarcoidosis in predisposed individuals. Here we review the literature on sarcoidosis elicited in the context of IFN-α therapy and propose a new link between the endogenous expression of IFN-α and the induction of disease manifestations in injured skin. © 2013 S. Karger AG, Basel.

Etude des jeunes consommateurs de drogues dures à Bienne et Berne

[Table des matières] 1. Introduction. 2. Résultats. 2.1. Taux de participation. 2.2. Nationalité et migration. 2.3. Antécédents et rapports familiaux. 2.4. Vie sociale et relations avec les pairs. 2.5. Parcours scolaire, vie active et formation professionnelle. 2.6. Santé physique. 2.7. Santé psychique. 2.8. Consommation de drogues. 2.9. Traitement de substitution. 2.10. Partage de seringues et overdoses. 2.11. Relations sexuelles et partenaires. 2.12. Comportement délinquant/criminel. 2.13. Besoins. 3. Conclusions. 4. Recommandations. 5. Annexes. 5.1. Questionnaire quantitatif. 5.2. Grille d'entretien pour les entretiens qualitatifs. 5.3. Grille pour les focus groupes. 5.4. Synthèse des entretiens de six professionnels des structures de soins de Berne.

Neurologie [Therapeutic advances in neurology].

The neurology field has been greatly improved in 2008. The therapeutic window of intravenous thrombolysis for acute ischemic stoke is extended to 4 h 30. New studies show that the clinical progression of Parkinson's disease might be slowed by some medication. Deep brain stimulation may be beneficial early in the course of the disease. Tysabri and Fingolimod in multiple sclerosis are discussed. The pharmacopoeia for epilepsy is in constant development with new products recently released in Switzerland. CGRP receptor antagonists are about to be launched as a promising acute migraine treatment. The pharmacological approach in amyotrophic lateral sclerosis patients might be improved according to research results.

Selective in vivo visualization of immune-cell infiltration in a mouse model of autoimmune myocarditis by fluorine-19 cardiac magnetic resonance.

BACKGROUND: The goal of this study was to characterize the performance of fluorine-19 ((19)F) cardiac magnetic resonance (CMR) for the specific detection of inflammatory cells in a mouse model of myocarditis. Intravenously administered perfluorocarbons are taken up by infiltrating inflammatory cells and can be detected by (19)F-CMR. (19)F-labeled cells should, therefore, generate an exclusive signal at the inflamed regions within the myocardium. METHODS AND RESULTS: Experimental autoimmune myocarditis was induced in BALB/c mice. After intravenous injection of 2×200 µL of a perfluorocarbon on day 19 and 20 (n=9) after immunization, in vivo (19)F-CMR was performed at the peak of myocardial inflammation (day 21). In 5 additional animals, perfluorocarbon combined with FITC (fluorescein isothiocyanate) was administered for postmortem immunofluorescence and flow-cytometry analyses. Control experiments were performed in 9 animals. In vivo (19)F-CMR detected myocardial inflammation in all experimental autoimmune myocarditis-positive animals. Its resolution was sufficient to identify even small inflammatory foci, that is, at the surface of the right ventricle. Postmortem immunohistochemistry and flow cytometry confirmed the presence of perfluorocarbon in macrophages, dendritic cells, and granulocytes, but not in lymphocytes. The myocardial volume of elevated (19)F signal (rs=0.96; P<0.001), the (19)F signal-to-noise ratio (rs=0.92; P<0.001), and the (19)F signal integral (rs=0.96; P<0.001) at day 21 correlated with the histological myocarditis severity score. CONCLUSIONS: In vivo (19)F-CMR was successfully used to visualize the inflammation specifically and robustly in experimental autoimmune myocarditis, and thus allowed for an unprecedented insight into the involvement of inflammatory cells in the disease process.

Photodynamic therapy enhances lipodoxorubcin distribution in sarcoma lung metastasis by lowering tumor interstitial fluid pressure in a rodent model

Objective: The management of sarcoma metastasis by systemic chemotherapy is often unsatisfactory. This has paradoxally been attributed to the leakiness of tumor neovessels which induce high intratumor interstitial fluid pressure (IFP) and limit convection forces that are important for drug distribution. In a rodent model, we have recently shown that photodynamic (PDT) pre treatment of lung metastasis could enhance their uptake of chemotherapy. We hypothesized that PDT transiently decreases tumor IFP which enhances convection and promotes drug distribution.Methods: Sarcoma tumors were generated sub-pleurally in the lungs of 12 rats. Animals were randomized at 10 days into i. no pre-treatment (control) and ii. low dose PDT pre-treatment (0・0625 mg/kg Visudyne, 10J/cm2 and 35 mW/cm2) followed by intravenous Liposomal doxorubicin (LiporubicinTM) administration. Using the wick-in-needle technique, we determined tumor and normal tissue IFP before, during and after PDT. In parallel, the uptake of LiporubicinTM was determined by high performance liquid chromatography in tumor and lung tissues.Results: Tumor IFP was significantly higher than normal tissue IFP in all animals. PDT pre-treatment did not affect normal tissue IFP but caused a significant decrease in tumor IFP (mean decrease by 2+/− 1mmHg) which lasted an average of 30 minutes before reaching baseline values. Tumor but not normal lung tissue LiporubicinTM uptake was significantly increased by 67% with PDT pre-treatment when liporubicin was allowed to circulate for one hour.Conclusion: Photodynamic therapy pre-treatment enhances LiporubicinTM uptake in sarcoma lung metastasis by transiently decreasing tumor IFP. These PDT conditions seem to specifically modulate tumor neovessels but not normal lung vessels.

Late onset tacrolimus-induced life-threatening polyneuropathy in a kidney transplant recipient patient

A 59-year-old kidney recipient was diagnosed with a late onset of severe chronic inflammatory demyelinating polyradiculoneuropathy and almost fully recovered after stopping tacrolimus and one course of intravenous immunoglobulin treatment. Unique features of this patient are the unusually long time lapse between initiation of tacrolimus and the adverse effect (10 years), a strong causality link and several arguments pointing toward an inflammatory etiology. When facing new neurological signs and symptoms in graft recipients, it is important to bear in mind the possibility of a drug-induced adverse event. Discontinuation of the suspect drug and immunomodulation are useful treatment options.

Sclerotherapy of telangiectasias: a painless two-step technique.

BACKGROUND: Sclerotherapy of telangiectasias and reticular leg veins can be unpleasant and painful for some patients. OBJECTIVE: To determine pain level with two different sclerotherapy techniques in a prospective randomized trial. METHODS: Patients with symmetrical telangiectasias and reticular veins on both legs (C(1A) or (S)E(P)A(S)P(N1) were randomized to the standard (successive injections of chromated glycerin mixed with one-third lidocaine-epinephrine 1%) or two-step technique (first treating only reticular veins with a single injection at the base of each cluster of telangiectasias and then successively injecting all remaining telangiectasias a few minutes later. Pain was assessed using a 100-point visual analogue scale (0 = no pain, 100 = maximum pain). RESULTS: Data from 53 consecutive patients could be evaluated. The two-step technique was significantly less painful (28.2) than the standard technique (40.6, p < .001). CONCLUSION: The two-step technique with chromated glycerin mixed with one-third lidocaine-epinephrine 1% significantly reduces sclerotherapy pain. This may be a useful technique for patients who are particularly sensitive or afraid of sclerotherapy.

Effects of beta-blockade on energy metabolism following burns.

The purpose of this study was to compare the effects of propranolol administered either by i.v. infusion or by prolonged oral administration (4 days) during the first 3 weeks following burns. The resting metabolic rate (RMR) of 10 non-infected fasting burned patients (TBSA: 28 per cent, range 18-37 per cent) was determined four times consecutively by indirect calorimetry (open circuit hood system) following: (1) i.v. physiological saline; (2) i.v. propranolol infusion (2 micrograms/kg/min following a bolus of 80 micrograms/kg); (3) oral propranolol (40 mg q.i.d. during 4 +/- 1 days); and (4) in control patients. All patients showed large increases in both RMR (144 +/- 2 per cent of reference values) and in urinary catecholamine excretion (three to four times as compared to control values). The infusion of propranolol induced a significant decrease in RMR to 135 +/- 2 per cent and oral propranolol to 129 +/- 3 per cent of reference values. A decrease in lipid oxidation but no change in carbohydrate and protein oxidation were observed during propranolol administration. It is concluded that the decrease in RMR induced by propranolol was not influenced by the route of administration. The magnitude of the decrease in energy expenditure suggests that beta-adrenergic hyperactivity represents only one of the mediators of the hypermetabolic response to burn injury.

Traitements de fer: preuves de t'efficacité et bonne pratique clinique [Iron therapy: proof of efficacy and good clinical practice].

Efficacy of iron therapy, whether oral or intravenous, on biological markers of body iron stores is well recognized in medical literature, but current studies are heterogeneous, of sometimes dubious quality, and rarely address clinical outcomes. Precise practical guidelines appear available only for indications related to kidney disease. First-line intravenous use is reserved for situations comprising chronic renal failure, or patients presenting with malabsorption syndromes such as in inflammatory bowel disease. In all other situations, because of the non-negligible risk of hypersensitivity reactions, intravenous iron use is considered justified only in clinically sustained indications, for patients in whom oral administration of iron is unsatisfactory or impossible.

Central line sepsis in intensive care units : overview and update

Catheter-related infection remains a leading cause of nosocomial infections, particularly in intensive care units. It includes colonization of the device, skin exit-site infection and device- or catheter-related bloodstream infection. The latter represents the most frequent life-threatening associated complication of central venous catheter use and is associated with significant patient morbidity, mortality and extra hospital costs. The incidence of catheter-related bloodstream infection ranges from 2 to 14 episodes per 1000 catheter-days. On average, microbiologically-documented device-related bloodstream infections complicate from three to five per 100 central venous line uses, but they only represent the visible part of the iceberg and most clinical sepsis are nowadays considered to be catheter-related. We briefly review the pathophysiology of infection, highlighting the importance of the skin insertion site and of intravenous line hub as principal sources of colonization. Principles of therapy are reviewed. Several preventive approaches are also discussed, in particular the possible benefit of recently developed impregnated catheters. Finally, the potential positive impact of a multimodal global preventive strategy based on strict application of hygienic rules is presented.

Faut-il traiter l'osteoporose liee a la thalassemie majeure: deux cas cliniques [Should we treat thalassemia-induced osteoporosis: two case reports].

We report two cases of beta-thalassemia-induced osteoporosis. A man and a woman presented an osteoporosis at the densitometry and were treated with bisphoshonate iv. All the studies analysed the efficacity of bisphosphonate, in particular zoledronate seems to be effective. Concerning the pathogenesis, the RANK-RANK-Ligand and OPG play a major role in bone-resorption and seem to be the principal implicated mechanism for the development of osteoporosis in BTM. At the moment there is no study evaluating the efficacity of denosumab in the BTM.