993 resultados para Sepsis, drug therapy


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Switzerland has a low mortality rate from cardiovascular diseases, but little is known regarding prevalence and management of cardiovascular risk factors (CV RFs: hypertension, hypercholesterolemia and diabetes) in the general population. In this study, we assessed 10-year trends in self-reported prevalence and management of cardiovascular risk factors in Switzerland. data from three national health interview surveys conducted between 1997 and 2007 in representative samples of the Swiss adult population (49,261 subjects overall). Self-reported CV RFs prevalence, treatment and control levels were computed. The sample was weighted to match the sex - and age distribution, geographical location and nationality of the entire adult population of Switzerland. self-reported prevalence of hypertension, hypercholesterolemia and diabetes increased from 22.1%, 11.9% and 3.3% in 1997 to 24.1%, 17.4% and 4.8% in 2007, respectively. Prevalence of self-reported treatment among subjects with CV RFs also increased from 52.1%, 18.5% and 50.0% in 1997 to 60.4%, 38.8% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Self-reported control levels increased from 56.4%, 52.9% and 50.0% in 1997 to 80.6%, 75.1% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Finally, screening during the last 12 months increased from 84.5%, 86.5% and 87.4% in 1997 to 94.0%, 94.6% and 94.1% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. in Switzerland, the prevalences of self-reported hypertension, hypercholesterolemia and diabetes have increased between 1997 and 2007. Management and screening have improved, but further improvements can still be achieved as over one third of subjects with reported CV RFs are not treated.

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Crude ethanolic extracts (CEEs) from two species of Cucurbitaceae, Cucurbita maxima and Momordica charantia (commonly called "abóbora moranga" and melão de São Caetano", respectively) were assayed for antimalarial activity by the 4-d suppressive test. The CEE of dry C. maxima seeds showed strong antimalarial activity following oral administration (259 and 500 mg/kg), reducing by 50% the levels of parasistemia in Plasmodium berghey-infected mice. Treatment of normal animals with 500 mg/Kg of the extract three days before intravenous injection of P. berghei caused a significant 30% reduction in parasitemic levels. No effect was observed when the animals were treated with the CEE only on the day of inoculation. Oral administration of the CEE of dry M. charantia leaves adminstered orally was ineffective up to 500 mg/Kg in lowering the parasitemic levels of malarious mice.

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OBJECTIVE: To assess the molecular epidemiology and risk factors of predominant clones and sporadic strains of methicillin-resistant Staphylococcus aureus (MRSA) in Swiss hospitals and to compare them with European strains of epidemic clones. MATERIAL AND METHODS: One-year national survey of MRSA cases. Analysis of epidemiological and molecular typing data (PFGE) of MRSA strains. RESULTS: In 1997, 385 cases of MRSA were recorded in the five Swiss university hospitals and in 47 community hospitals. Half of the cases were found in Geneva hospitals where MRSA was already known to be endemic. Molecular typing of 288 isolates (one per case) showed that 186 (65%) belong to four predominant clones, three of which were mostly present in Geneva hospitals. In contrast, the fourth clone (85 cases) was found in 23 hospitals (in one to 16 cases per hospital). The remaining 35% of the strains were clustered into 62 pulsed field gel electrophoresis types. They accounted for one to five patients per hospital and were defined as sporadic. Multivariate analysis revealed no independent risk factors for harboring a predominant versus a sporadic strain, except that transfer from a foreign hospital increases the risk of harboring a sporadic strain (OR, 42; 95% CI, 5-360). CONCLUSION: While cases with predominant clones were due to the local spread of these clones, most sporadic cases appear to be due to the continuous introduction of new strains into the country. With the exception of a transfer from a hospital outside Switzerland, no difference in the clinical or epidemiological characteristics was observed between patients harboring a predominant clone and those with a sporadic strain.

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The significant development of immunosuppressive drug therapies within the past 20 years has had a major impact on the outcome of clinical solid organ transplantation, mainly by decreasing the incidence of acute rejection episodes and improving short-term patient and graft survival. However, long-term results remain relatively disappointing because of chronic allograft dysfunction and patient morbidity or mortality, which is often related to the adverse effects of immunosuppressive treatment. Thus, the induction of specific immunological tolerance of the recipient towards the allograft remains an important objective in transplantation. In this article, we first briefly describe the mechanisms of allograft rejection and immune tolerance. We then review in detail current tolerogenic strategies that could promote central or peripheral tolerance, highlighting the promises as well as the remaining challenges in clinical transplantation. The induction of haematopoietic mixed chimerism could be an approach to induce robust central tolerance, and we describe recent encouraging reports of end-stage kidney disease patients, without concomitant malignancy, who have undergone combined bone marrow and kidney transplantation. We discuss current studies suggesting that, while promoting peripheral transplantation tolerance in preclinical models, induction protocols based on lymphocyte depletion (polyclonal antithymocyte globulins, alemtuzumab) or co-stimulatory blockade (belatacept) should, at the current stage, be considered more as drug-minimization rather than tolerance-inducing strategies. Thus, a better understanding of the mechanisms that promote peripheral tolerance has led to newer approaches and the investigation of individualized donor-specific cellular therapies based on manipulated recipient regulatory T cells.

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Purpose of review: This review discusses demyelinating events of the nervous system that have been associated with new immunomodulatory treatments, in particular monoclonal antibodies (mAbs). Recent findings: Natalizumab, a mAb targeting the alpha-4 integrins, which is efficient in relapsing-remitting multiple sclerosis, has been associated with progressive multifocal leukoencephalopathy (PML). We will review the putative mechanisms linking natalizumab with JC virus, the agent of PML. Efalizumab, a mAb targeting a member of the integrin family, CD11a, was approved for the treatment of psoriasis, but had to be withdrawn in 2009 because of the occurrence of three cases of PML. Rituximab, an anti-CD20 mAb, is used in different neoplastic and autoimmune diseases and may soon enter the pharmacopeia of multiple sclerosis. It has been suggested that rituximab is a risk factor for PML; however, evidence of such a link is unclear. Antitumor necrosis factor-alpha agents are used in several autoimmune diseases. Several cases of demyelinating events of the nervous system have been reported, prompting a heightened surveillance of treated patients. Recent data are reassuring, suggesting that the incidence of such events is relatively low. Summary: Neurologists must become familiar with neurological complications of new immunomodulatory treatments, a field situated at the interface of neurology, immunology and infection.

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In Rendu-Osler disease, haemorrhages due to gastrointestinal vascular malformations are common. Surgical and endoscopic treatments for haemorrhage due to gastrointestinal vascular malformations are compromised when lesions are diffuse, escape identification or are inaccessible to treatment. Hormonal treatment with oestrogen and progestagens is still controversial based on contradictory results from two randomised clinical trials. Although somatostatin and its long-acting analogue, octreotide, have been reported to be beneficial in preventing rebleeding, there is no consensus on this type of treatment. This case report shows how the combination of ethinyloestradiol and norethisterone markedly reduced the need for blood transfusions with few side effects in one patient; in comparison, octreotide seems less effective but this could be related to a worsening of the disease.

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One of the most relevant concerns in long-term survivors of paediatric acute lymphoblastic leukaemia (ALL) is the development of neuropsychological sequelae. The majority of the published studies report on patients treated with chemotherapy and prophylactic central nervous system (CNS) irradiation, little is known about the outcome of patients treated with chemotherapy-only regimens. Using the standardised clinical and neuropsychological instruments of the SPOG Late Effects Study, the intellectual performance of 132 paediatric ALL patients treated with chemotherapy only was compared to that of 100 control patients surviving from diverse non-CNS solid tumours. As a group, ALL and solid tumour survivors showed normal and comparable intellectual performances (mean global IQ 104.6 in both groups). The percentage of patients in the borderline range (global IQ between 70 and 85) was comparable and not higher as expected (10% cases and 13% controls, expected 16%). Only 2 (2%) of the former ALL and 1 (1%) of the solid tumour patients were in the range of mental retardation (global IQ<70). Former known risk factors described in children treated with prophylactic CNS irradiation, like a younger age at diagnosis of ALL and female gender, remained valid in chemotherapy-only treated patients. The abandonment of prophylactic CNS irradiation and its replacement by a more intensive systemic and intrathecal chemotherapy led to a reduction, but not the disappearance of late neuropsychological sequelae.

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BACKGROUND: Depending on its magnitude, lower body negative pressure (LBNP) has been shown to induce a progressive activation of neurohormonal, renal tubular, and renal hemodynamic responses, thereby mimicking the renal responses observed in clinical conditions characterized by a low effective arterial volume such as congestive heart failure. Our objective was to evaluate the impact of angiotensin II receptor blockade with candesartan on the renal hemodynamic and urinary excretory responses to a progressive orthostatic stress in normal subjects. METHODS: Twenty healthy men were submitted to three levels of LBNP (0, -10, and -20 mbar or 0, -7.5, and -15 mm Hg) for 1 hour according to a crossover design with a minimum of 2 days between each level of LBNP. Ten subjects were randomly allocated to receive a placebo and ten others were treated with candesartan 16 mg orally for 10 days before and during the three levels of LBNP. Systemic and renal hemodynamics, renal sodium excretions, and the hormonal response were measured hourly before, during, and for 2 hours after LBNP. RESULTS: During placebo, LBNP induced no change in systemic and renal hemodynamics, but sodium excretion decreased dose dependently with higher levels of LBNP. At -20 mbar, cumulative 3-hour sodium balance was negative at -2.3 +/- 2.3 mmol (mean +/- SEM). With candesartan, mean blood pressure decreased (76 +/- 1 mm Hg vs. 83 +/- 3 mm Hg, candesartan vs. placebo, P < 0.05) and renal plasma flow increased (858 +/- 52 mL/min vs. 639 +/- 36 mL/min, candesartan vs. placebo, P < 0.05). Glomerular filtration rate (GFR) was not significantly higher with candesartan (127 +/- 7 mL/min in placebo vs. 144 +/- 12 mL/min in candesartan). No significant decrease in sodium and water excretion was found during LBNP in candesartan-treated subjects. At -20 mbar, the 3-hour cumulative sodium excretion was + 4.6 +/- 1.4 mmol in the candesartan group (P= 0.02 vs. placebo). CONCLUSION: Selective blockade of angiotensin II type 1 (AT1) receptors with candesartan increases renal blood flow and prevents the antinatriuresis during sustained lower body negative pressure despite a modest decrease in blood pressure. These results thus provide interesting insights into potential benefits of AT1 receptor blockade in sodium-retaining states such as congestive heart failure.

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BACKGROUND: The availability of a rapid diagnostic test for malaria (RDTm) allows accurate diagnosis at all levels of health facilities. The objective of the present study was to evaluate the safety of withholding antimalarials in febrile children who have a negative test result. METHODS: We conducted a prospective 2-arm longitudinal study in areas of Tanzania that are moderately and highly endemic for malaria. Children with a history of fever were managed routinely by resident clinicians of 2 health facilities, except that no antimalarials were prescribed if the RDTm result was negative. Children were followed up at home on day 7. The main outcome was the occurrence of complications in children with negative RDTm results; children with positive RDTm results were followed up for the same outcomes for indirect comparison. RESULTS: One thousand children (median age, 24 months) were recruited. Six hundred three children (60%) had a negative RDTm result. Five hundred seventy-three (97%) of these children were cured on day 7. Forty-nine (8%) of the children with negative RDTm results spontaneously visited the dispensary before day 7, compared with 10 (3%) of the children with positive RDTm results. All children who had negative initial results had negative results again when they were tested either at spontaneous attendance or on day 7 because they were not cured clinically, except for 3 who gave positive results on days 2, 4, and 7 respectively but who did not experience any complication. Four children who had negative initial results were admitted to the hospital subsequently, all with negative results for malaria tests upon admission. Two of them died, of causes other than malaria. CONCLUSIONS: Not giving antimalarial drugs in febrile children who had a negative RDTm result was safe, even in an area highly endemic for malaria. Our study provides evidence for treatment recommendations based on parasitological diagnosis in children <5 years old.

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Trilateral retinoblastoma (TRB) is a rare condition characterized by an intracranial neuroblastic tumor associated with bilateral or unilateral retinoblastoma (RB). The outcome is almost always fatal. An 18-month-old patient with familial bilateral RB was referred for a pineal lesion detected on a screening by magnetic resonance imaging. The child, considered inoperable by 2 different neurosurgical teams, was treated with conventional chemotherapy (methotrexate, vincristine, vepeside, cyclophosphamide, and carboplatin) plus tandem transplantation (vepeside/carboplatin and thiotepa/mephalan) followed by local radiotherapy. At 80 months from the diagnosis of TRB, the patient is alive and in complete remission, with no neuropsychologic consequences. An early and aggressive treatment may improve the prognosis of TRB.

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Brucellosis has become a rare entity in many industrialised countries, because of animal vaccination programs. We report a first case in the literature of Brucella abscess in the hip region observed in Switzerland in a subject without any clear risk factor, leading us to conclude that abscess formation can be a rare manifestation of brucellosis. Because it can present in many different forms and locations without having characteristic clinics, a high index of suspicion is needed for the diagnosis even if the patient is a healthy athlete with no clear way of obvious route for contamination, and this even more if all the common causes of athletic hip pain have been ruled out.

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Invasive candidiasis (IC) is a relatively common syndrome in neonates and children and is associated with significant morbidity and mortality. These guidelines provide recommendations for the prevention and treatment of IC in neonates and children. Appropriate agents for the prevention of IC in neonates at high risk include fluconazole (A-I), nystatin (B-II) or lactoferrin ± Lactobacillus (B-II). The treatment of IC in neonates is complicated by the high likelihood of disseminated disease, including the possibility of infection within the central nervous system. Amphotericin B deoxycholate (B-II), liposomal amphotericin B (B-II), amphotericin B lipid complex (ABLC) (C-II), fluconazole (B-II), micafungin (B-II) and caspofungin (C-II) can all be potentially used. Recommendations for the prevention of IC in children are largely extrapolated from studies performed in adults with concomitant pharmacokinetic data and models in children. For allogeneic HSCT recipients, fluconazole (A-I), voriconazole (A-I), micafungin (A-I), itraconazole (B-II) and posaconazole (B-II) can all be used. Similar recommendations are made for the prevention of IC in children in other risk groups. With several exceptions, recommendations for the treatment of IC in children are extrapolated from adult studies, with concomitant pharmacokinetic studies. Amphotericin B deoxycholate (C-I), liposomal amphotericin B (A-I), ABLC (B-II), micafungin (A-I), caspofungin (A-I), anidulafungin (B-II), fluconazole (B-I) and voriconazole (B-I) can all be used.

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BACKGROUND: To evaluate the effect of statins on the annual expansion rate (ER) of small infrarenal abdominal aortic aneurysms (AAA). PATIENTS AND METHODS: All patients under regular surveillance for small AAA between January 2000 and September 2007, in the Department of Angiology, Lausanne University Hospital, were included. Inclusion criteria were baseline abdominal aortic diameter between 25 and 55 mm, at least two measurements of AAA diameter and a minimum follow up of 6 months. Patients with Marfan disease, infectious or inflammatory AAA, and patients with prior AAA repair were excluded. The influence of statin use and other factors on ER were examined by bivariate and multivariate analysis. RESULTS: Among 589 patients who underwent an abdominal aorta evaluation, 94 patients (89 % men, mean age 69.1 years) were finally included in the analysis. Baseline AAA size was 39.9 ± 7.7 mm (mean±SE) and 48.7 ± 8.4 mm at end of follow-up. Patients had a regular aneurysm size assessment during 38.5 ± 27.7 months. Mean ER was 3.59 mm/y (± 2.81). The 50 patients who were treated with statin during the study period had a lower ER compared to the 44 controls (2.91 vs 4.37 mm/year, p = 0.01). CONCLUSIONS: This study confirms the considerable individual variations in the AAA expansion rate, and emphasizes the need for regular aortic diameter assessments. In this study, patients treated with statin demonstrate a significant decrease in the ER compared to controls. This finding need to be evaluated in prospective interventional studies powered to demonstrate the potential benefit of statin treatment.

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When a severe elevation of blood pressure occurs in conjunction with failure of a target organ, immediate referral of the patient to hospital is an easy decision for the primary care physician. However, when severe elevation of blood pressure is observed in the absence of any significant symptom, it is a much more difficult decision to take. Indeed, if some clinical situations require an immediate and aggressive anti-hypertensive therapy, such a treatment can be clearly deleterious for a number of other cases. This paper attempts to clarify in which situations the primary care physician should refer hypertensive crisis to the emergency department.