275 resultados para long-term studies
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RATIONALE: A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a well-documented neurobiological finding in major depression. Moreover, clinically effective therapy with antidepressant drugs may normalize the HPA axis activity. OBJECTIVE: The aim of this study was to test whether citalopram (R/S-CIT) affects the function of the HPA axis in patients with major depression (DSM IV). METHODS: Twenty depressed patients (11 women and 9 men) were challenged with a combined dexamethasone (DEX) suppression and corticotropin-releasing hormone (CRH) stimulation test (DEX/CRH test) following a placebo week and after 2, 4, and 16 weeks of 40 mg/day R/S-CIT treatment. RESULTS: The results show a time-dependent reduction of adrenocorticotrophic hormone (ACTH) and cortisol response during the DEX/CRH test both in treatment responders and nonresponders within 16 weeks. There was a significant relationship between post-DEX baseline cortisol levels (measured before administration of CRH) and severity of depression at pretreatment baseline. Multiple linear regression analyses were performed to identify the impact of psychopathology and hormonal stress responsiveness and R/S-CIT concentrations in plasma and cerebrospinal fluid (CSF). The magnitude of decrease in cortisol responsivity from pretreatment baseline to week 4 on drug [delta-area under the curve (AUC) cortisol] was a significant predictor (p<0.0001) of the degree of symptom improvement following 16 weeks on drug (i.e., decrease in HAM-D21 total score). The model demonstrated that the interaction of CSF S-CIT concentrations and clinical improvement was the most powerful predictor of AUC cortisol responsiveness. CONCLUSION: The present study shows that decreased AUC cortisol was highly associated with S-CIT concentrations in plasma and CSF. Therefore, our data suggest that the CSF or plasma S-CIT concentrations rather than the R/S-CIT dose should be considered as an indicator of the selective serotonergic reuptake inhibitors (SSRIs) effect on HPA axis responsiveness as measured by AUC cortisol response.
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Introduction: We previously reported the results of a phase II study for patients with newly diagnosed primary CNS lymphoma (PCNSL) treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and responseadapted whole brain radiotherapy (WBRT). The purpose of this report is to update the initial results and provide long-term data regarding overall survival, prognostic factors, and the risk of treatment-related neurotoxicity.Methods: A long-term follow-up was conducted on surviving primary central nervous system lymphoma patients having been treated according to the ,,OSHO-53 study", which was initiated by the Ostdeutsche Studiengruppe Hamatologie-Onkologie. Between August 1999 and October 2004 twentythree patients with an average age of 55 and median Karnofsky performance score of 70% were enrolled and received high-dose mthotrexate (HD-MTX) on days 1 and 10. In case of at least a partial remission (PR), high-dose busulfan/ thiotepa (HD-BuTT) followed by aPBSCT was performed. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. All patients (n=8), who are alive in 2011, were contacted and Mini Mental State examination (MMSE) and the EORTC QLQ-C30 were performed.Results: Eight patients are still alive with a median follow-up of 116,9 months (79 - 141, range). One of them suffered from a late relapse eight and a half years after initial diagnosis of PCNSL, another one suffers from a gall bladder carcinoma. Both patients are alive, the one with the relapse of PCNSL has finished rescue therapy and is further observed, the one with gall baldder carcinoma is still under therapy. MMSE and QlQ-C30 showed impressive results in the patients, who were not irradiated. Only one of the irradiated patients is still alive with a clear neurologic deficit but acceptable quality of life.Conclusions: Long-term follow-up of our patients, who were included in the OSHO-53 study show an overall survival of 30 percent. If WBRT can be avoided no long-term neurotoxicity has been observed and the patients benefit from excellent Quality of Life. Induction chemotherapy with two cycles of HD-MTX should be intensified to improve the unsatisfactory OAS of 30 percent.
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The question of why some social systems have evolved close inbreeding is particularly intriguing given expected short- and long-term negative effects of this breeding system. Using social spiders as a case study, we quantitatively show that the potential costs of avoiding inbreeding through dispersal and solitary living could have outweighed the costs of inbreeding depression in the origin of inbred spider sociality. We further review the evidence that despite being favored in the short term, inbred spider sociality may constitute in the long run an evolutionary dead end. We also review other cases, such as the naked mole rats and some bark and ambrosia beetles, mites, psocids, thrips, parasitic ants, and termites, in which inbreeding and sociality are associated and the evidence for and against this breeding system being, in general, an evolutionary dead end.
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ABSTRACT: BACKGROUND: The dissemination of palliative care for patients presenting complex chronic diseases at various stages has become an important matter of public health. A death census in Swiss long-term care facilities (LTC) was set up with the aim of monitoring the frequency of selected indicators of palliative care. METHODS: The survey covered 150 LTC facilities (105 nursing homes and 45 home health services), each of which was asked to complete a questionnaire for every non-accidental death over a period of six months. The frequency of 4 selected indicators of palliative care (resort to a specialized palliative care service, the administration of opiates, use of any pain measurement scale or other symptom measurement scale) was monitored in respect of the stages of care and analysed based on gender, age, medical condition and place of residence. RESULTS: Overall, 1200 deaths were reported, 29.1% of which were related to cancer. The frequencies of each indicator varied according to the type of LTC, mostly regarding the administration of opiate. It appeared that the access to palliative care remained associated with cancer, terminal care and partly with age, whereas gender and the presence of mental disorders had no effect on the indicators. In addition, the use of drugs was much more frequent than the other indicators. CONCLUSION: The profile of patients with access to palliative care must become more diversified. Among other recommendations, equal access to opiates in nursing homes and in home health services, palliative care at an earlier stage and the systematic use of symptom management scales when resorting to opiates have to become of prime concern.
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Matrix effects, which represent an important issue in liquid chromatography coupled to mass spectrometry or tandem mass spectrometry detection, should be closely assessed during method development. In the case of quantitative analysis, the use of stable isotope-labelled internal standard with physico-chemical properties and ionization behaviour similar to the analyte is recommended. In this paper, an example of the choice of a co-eluting deuterated internal standard to compensate for short-term and long-term matrix effect in the case of chiral (R,S)-methadone plasma quantification is reported. The method was fully validated over a concentration range of 5-800 ng/mL for each methadone enantiomer with satisfactory relative bias (-1.0 to 1.0%), repeatability (0.9-4.9%) and intermediate precision (1.4-12.0%). From the results obtained during validation, a control chart process during 52 series of routine analysis was established using both intermediate precision standard deviation and FDA acceptance criteria. The results of routine quality control samples were generally included in the +/-15% variability around the target value and mainly in the two standard deviation interval illustrating the long-term stability of the method. The intermediate precision variability estimated in method validation was found to be coherent with the routine use of the method. During this period, 257 trough concentration and 54 peak concentration plasma samples of patients undergoing (R,S)-methadone treatment were successfully analysed for routine therapeutic drug monitoring.
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Objectif: La réparation de la valve mitrale constitue le traitement de choix pour restaurer ta fonction de celle-ci. Elle est actuellement reconnue pour garantir une bonne évolution à long terme. Dans le but de faciliter les décisions périopératoires, nous avons analysé nos patients afin de déterminer les facteurs de risque ayant affecté leur évolution. Méthodes: Nous avons étudié rétrospectivement 175 premiers patients consécutifs (âge moyen : 64 +/-10.4 ans ;113 hommes) qui ont subi une réparation primaire de la valve mitrale associée à toute autre intervention cardiaque entre 1986 et 1998. Les facteurs de risque influençant le taux de réopération et la survie à long terme ont été analysés de manière uni et multivariée. Résultats: La mortalité opératoire était de 3.4 % (6 décès, 0 -22 et jours post-opératoires). La mortalité tardive était de 9.1 % (16 décès, 3e-125e mois post-opératoires). Cinq patients ont dû être réopérés. L'analyse actuarielle selon Kaplan-Meier a montré une survie à 1 année de 96 +l-1 %, une survie à 5 ans de 88 +/- 3 % et une survie à 10 ans de 69 +/- 8 %. Après 1 année, la fraction de population sans réopération était de 99 %, elle était de 97 +/-2 % après 5 ans et de 88+/-6 % après 10 ans. L'analyse multivariée a montré qu' un stade NYHA III et IV résiduel ( p=0.001, RR 4.55, 95 % IC :1.85 -14.29), une mauvaise fraction d'éjection préopératoire(p=0.013, RR 1.09, 95 % IC 1.02 -1.18), ,une régurgitation mitrale d'origine fonctionnelle (p=0.018, RR 4.17, 95% IC 1.32-16.67) ainsi qu'une étiologie ischémique (p=0.049, RR 3.13, 95% IC 1.01-10.0) constituaient tous des prédicteurs indépendant de mortalité. Une régurgitation mitrale persistante au 7 e jour post-opératoire (p= 0.005, RR 4.55, 95 % IC :1.56 -20.0), un âge inférieur à 60 ans (p = 0.012, RR 8.7, 95 % IC 2.44 - 37.8) et l'absence d'anneau prothétique (p = 0.034, RR 4.76, 95 % IC 1.79-33.3) se sont tous révélés être des facteurs de risque indépendant de réopération. Conclusion: Les réparations mitrales sont accompagnées d'une excellente survie à long terme même si leur évolution peut être influencée négativement par de nombreux facteurs de risques periopératoires. Les risques de réopération sont plus élevés chez des patients jeunes présentant une régurgitation mitrale résiduelle et n'ayant pas bénéficié de la mise en place d'un anneau prothétique.
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Background: Bronchopulmonary dysplasia (BPD) remains the leading cause of chronic pulmonary morbidity among preterm neonates. However, the exact pathophysiology is still unknown. Here we present the first results from a new model inteAbstracts, 25th International Workshop on Surfactant Replacement 400 Neonatology 2010;97:395-400 grating the most common risk factors for BPD (lung immaturity, inflammation, mechanical ventilation (MV), oxygen), which allows long-term outcome evaluation due to a non-traumatic intubation procedure. Objectives: To test the feasibility of a new rat model by investigating effects of MV, inflammation and oxygen applied to immature lungs after a ventilation-free interval. Methods: On day 4, 5, or 6 newborn rats were given an intraperitoneal injection of lipopolysaccharides to induce a systemic inflammation. 24 h later they were anesthetized, endotracheally intubated and ventilated for 8 h with 60% oxygen. After weaning of anesthesia and MV the newborn rats were extubated and returned to their mothers. Two days later they were killed and outcome measurements were performed (histology, quantitative RT-PCR) and compared to animals investigated directly after MV. Results: Directly after MV, histological signs of ventilator-induced lung injury were found. After 48 h, the first signs of early BPD were seen with delayed alveolar formation. Expression of inflammatory genes was only transiently increased. After 48 h genes involved in alveolarization, such as matrix metalloproteinase-9 and tropoelastin, showed a significant change of their expression. Conclusion: For the first time we can evaluate in a newborn rat model the effects of MV after a ventilation-free interval. This allows discrimination between immediate response genes and delayed changes of expression of more structural genes involved in alveolarization.
Perineal stapled prolapse resection for external rectal prolapse: is it worthwhile in the long-term?
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BACKGROUND: Perineal stapled prolapse (PSP) resection is a novel operation for treating external rectal prolapse. However, no long-term results have been reported in the literature. This study analyses the long-term recurrence rate, functional outcome, and morbidity associated with PSP resection. METHODS: Nine consecutive patients undergoing PSP resection between 2007 and 2011 were prospectively followed. Surgery was performed by the same surgeons in a standardised technique. Recurrence rate, functional outcome, and complication grade were prospectively assessed. RESULTS: All 9 patients undergoing PSP resection were investigated. The median age was 72 years (range 25-88 years). No intraoperative complications occurred. Faecal incontinence, preoperatively present in 2 patients, worsened postoperatively in one patient (Vaizey 18-22). One patient developed new-onset faecal incontinence (Vaizey 18). The median obstructive defecation syndrome score decreased postoperatively significantly from 11 (median; range 8-13) to 5 (median; range 4-8) (p < 0.005). At a median follow-up of 40 months (range 14-58 months), the prolapse recurrence rate was 44 % (4/9 patients). CONCLUSIONS: The PSP resection is a fast and safe procedure associated with low morbidity. However, the poor long-term functional outcome and the recurrence rate of 44 % warrant a cautious patient selection.
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The purpose of this study was to assess the long-term outcomes of patients with polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA) without Five-Factor Score (FFS)-defined poor-prognosis factors (FFS=0) and enrolled in a prospective clinical trial. Patients were followed (2005-2012) under routine clinical care in an extended study and data were recorded prospectively. Long-term survival, disease-free survival (DFS), relapses, therapeutic responses and sequelae were analyzed. Mean±SD follow-up was 98.2±41.9months. After having initially received glucocorticoids (GC) alone, according to the study protocol, 82% (97/118) patients achieved remission but 18% (21/118) required ≥1 immunosuppressant(s) (IS) before 19/21 achieved remission. Two patients died before entering remission. After remission, 53% (61/116) patients relapsed 25.6±27.9months after starting treatment. The 5- and 8-year overall survival rates were 93% and 86%, respectively, with no difference between PAN and MPA, and between relapsers and nonrelapsers. DFS was shorter for MPA than PAN patients (P=0.02). Throughout follow-up, 47% of patients required ≥1 IS. At the last follow-up visit, 44% were still taking GC and 15% IS. The mean vasculitis damage index score was 1.9±1.9; the most frequent sequelae were peripheral neuropathy, hypertension and osteoporosis. For PAN or MPA patients without poor-prognosis factors at diagnosis and treated initially with GC alone, long-term survival was excellent. However, relapses remained frequent, requiring IS introduction for nearly half of the patients. To lower the frequencies of relapses and sequelae remains a challenge for FFS=0 PAN and MPA patients.
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Purpose: to describe a case of probable bilateral diffuse uveal melanocytic proliferation (BDUMP) with scleral involvement, free from systemic malignancies and cataract. Methods: fifty months of follow up with recurrent complete ophthalmological examinations, including fundus photography, fluorescein/indocyanine green angiography (FA) and optical coherence tomography (OCT). Investigations also included an electroretinography (ERG) and histological examination of scleral biopsy. Extraocular malignancies were repeatedly searched. Results: the patient was a 61 year-old Italian man with chronic hepatitis type C. At first visit his best corrected visual acuity (BCVA) was 20/32 in OS and 20/25 in OD. Funduscopy showed multiple patch-shaped pigmented alterations involving macular region and mid retinal periphery. FA showed corresponding areas of late-phase hyperfluorescent pinpoints (figure 1a, OS) and intemediate-phase hypocyanescence (figure 1b, OS), with subtle serous neurosensory retinal detachment confirmed by OCT. Photopic and scotopic ERG tested normal. Systemic prednisone was administered for one month without any improvement. After ten months round pigmentary lesions appeared also in superior scleral surface of both eyes. Biopsy allowed to disclose slightly pigmented spindle cells. BCVA worsened for further 10 months, with enlargement of FA alteration areas but lenses still clear. After 30 months spontaneous coalescence and atrophy of retinal lesions started, paralleled by progressive visual recovery. At the end of our follow up BCVA was 20/25 in OU while scleral pigmentary lesions remained unchanged. Conclusions: we report the case of a patient with main features of BDUMP and some unusual findings. Although not all classical diagnostic criteria were fulfilled, the presence of scleral pigmented lesions and spontaneous visual recovery may enlarge clinical spectrum of the disease.
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It has been suggested that an inappropriate relationship between renin and exchangeable sodium is responsible for the hypertension of patients with chronic renal failure. Long-term blockade of the renin system by captopril made it possible to test this hypothesis in 8 patients on maintenance hemodialysis. Captopril was administered orally in 2 daily doses of 25 to 200 mg. Previously, blood pressure averaged 179/105 +/- 6/3 (mean +/- SEM) pre- and 182/103 +/- 7/3 mm HG post-dialysis, despite intensive ultrafiltration and conventional antihypertensive therapy. The 4 patients with the highest plasma renin activity normalized their blood pressure with captopril alone, whereas in the 4 remaining patients, captopril therapy was complemented by salt subtraction which consisted in replacement of 1-2 liters of ultrafiltrate by an equal volume of 5% dextrose until blood pressure was controlled. After an average treatment period of 5 months, blood pressure of all 8 patients was reduced to 134/76 +/- 7/5 mm Hg (P less than 0.001) pre- and 144/81 +/- 9/5 mm Hg (P less than 0.001) post-dialysis without a significant change in body weight. The present data suggest that captopril alone or combined with salt subtraction normalizes blood pressure of patients on chronic hemodialysis with so called uncontrollable hypertension.
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In this review, we discuss the pharmacological and clinical properties of irbesartan, a noncompetitive angiotensin II receptor type 1 antagonist, successfully used for more than a decade in the treatment of essential hypertension. Irbesartan exerts its antihypertensive effect through an inhibitory effect on the pressure response to angiotensin II. Irbesartan 150-300 mg once daily confers a lasting effect over 24 hours, and its antihypertensive efficacy is further enhanced by the coadministration of hydrochlorothiazide. Additionally and partially beyond its blood pressure-lowering effect, irbesartan reduces left ventricular hypertrophy, favors right atrial remodeling in atrial fibrillation, and increases the likelihood of maintenance of sinus rhythm after cardioversion in atrial fibrillation. In addition, the renoprotective effects of irbesartan are well documented in the early and later stages of renal disease in type 2 diabetics. Furthermore, both the therapeutic effectiveness and the placebo-like side effect profile contribute to a high adherence rate to the drug. Currently, irbesartan in monotherapy or combination therapy with hydrochlorothiazide represent a rationale pharmacologic approach for arterial hypertension and early-stage and late-stage diabetic nephropathy in hypertensive type II diabetics.
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Pulsed-field gel electrophoresis (PFGE) is widely used for epidemic investigations of methicillin-resistant Staphylococcus aureus (MRSA). In the present study, we evaluated its use in a long-term epidemiological setting (years to few decades, country to continent level). The clustering obtained from PFGE patterns after SmaI digestion of the DNA of 20 strains was compared to that obtained using a phylogenetic typing method (multiprimer RAPD). The results showed that the analysis of small PFGE bands (10-85kb) correlates better with multiprimer RAPD than the analysis of large PFGE bands (>85-700kb), suggesting that the analysis of small bands would be more suitable for the investigation of long-term epidemiological setting. However, given the technical difficulties to obtain a good resolution of these bands and the putative presence of plasmids among them, PFGE does not appear to be a method of choice for the long-term epidemiology analysis of MRSA.