17 resultados para LONG-TERM TREATMENT

em Biblioteca Digital da Produção Intelectual da Universidade de São Paulo


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This long-term extension of an 8-week randomized, naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam (n = 47) and paroxetine (n = 37) over a 3-year total treatment duration. Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine (both taken at bedtime). This study reports data from the long-term period (34 months), following the initial 8-week treatment phase. Thus, total treatment duration was 36 months. Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine, but patients with partial primary treatment success were switched to the combination therapy. At initiation of the long-term study, the mean doses of clonazepam and paroxetine were 1.9 (SD, 0.30) and 38.4 (SD, 3.74) mg/d, respectively. These doses were maintained until month 36 (clonazepam 1.9 [ SD, 0.29] mg/d and paroxetine 38.2 [SD, 3.87] mg/d). Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)-Improvement rating than treatment with paroxetine (mean difference: CGI-Severity scale -3.48 vs -3.24, respectively, P = 0.02; CGI-Improvement scale 1.06 vs 1.11, respectively, P = 0.04). Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine (28.9% vs 70.6%, P < 0.001). The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course. There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events.

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Background: Abnormal regulation of glycogen synthase kinase 3-beta (GSK3B) activity has been implicated in the pathophysiology of mood disorders. Many pharmacological agents, including antidepressants, can modulate GSK3B. The aim of the present study was to investigate the effect of short-and long-term sertraline treatment on the expression and phosphorylation of GSK3B in platelets of patients with late-life major depression. Methods: Thirty-nine unmedicated elderly adults with major depressive disorder (MOD) were initially included in this study. The comparison group comprised 18 age-matched, healthy individuals. The expression of total and Ser-9 phosphorylated GSK3B (pGSK3B) was determined by Enzyme Immunometric Assay (EIA) in platelets of patients and controls at baseline, and after 3 and 12 months of sertraline treatments for patients only. During this period, patients were continuously treated with therapeutic doses of sertraline. GSK3B activity was indirectly estimated by calculating the proportion of inactive (phosphorylated) forms (pGSK3B) in relation to the total expression of the enzyme (i.e.. GSK3B ratio). Results: Depressed patients had significantly higher levels of pGSK3B as compared to controls (p < 0.001). Within the MDD group, after 3 months of sertraline treatment no significant changes were observed in GSK3B expression and phosphorylation state, as compared to baseline levels. However, after 12 months of treatment we found a significant increase in the expression of total GSK3B (p = 0.05), in the absence of any significant changes in pGSK3B (p = 0.12), leading to a significant reduction in GSK3B ratio (p = 0.001). Conclusions: Our findings indicate that GSK3B expression was upregulated by the continuous treatment with sertraline, along with an increment in the proportion of active forms of the enzyme. This is compatible with an increase in overall GSK3B activity, which may have been induced by the long-term treatment of late-life depression with sertraline. (C) 2012 Elsevier Ltd. All rights reserved.

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Diabetes mellitus is a product of low insulin sensibility and pancreatic beta-cell insufficiency. Rats with streptozotocin-induced diabetes during the neonatal period by the fifth day of age develop the classic diabetic picture of hyperglycemia, hypoinsulinemia, polyuria, and polydipsia aggravated by insulin resistance in adulthood. In this study, we investigated whether the effect of long-term treatment with melatonin can improve insulin resistance and other metabolic disorders in these animals. At the fourth week of age, diabetic animals started an 8-wk treatment with melatonin (1 mg/kg body weight) in the drinking water at night. Animals were then killing, and the sc, epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed, and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Blood samples were collected for biochemical assays. Melatonin treatment reduced hyperglycemia, polydipsia, and polyphagia as well as improved insulin resistance as demonstrated by constant glucose disappearance rate and homeostasis model of assessment-insulin resistance. However, melatonin treatment was unable to recover body weight deficiency, fat mass, and adipocyte size of diabetic animals. Adiponectin and fructosamine levels were completely recovered by melatonin, whereas neither plasma insulin level nor insulin secretion capacity was improved in diabetic animals. Furthermore, melatonin caused a marked delay in the sexual development, leaving genital structures smaller than those of nontreated diabetic animals. Melatonin treatment improved the responsiveness of adipocytes to insulin in diabetic animals measured by tests of glucose uptake (sc, EP, and RP), glucose oxidation, and incorporation of glucose into lipids (EP and RP), an effect that seems partially related to an increased expression of insulin receptor substrate 1, acetyl-coenzyme A carboxylase and fatty acid synthase. In conclusion, melatonin treatment was capable of ameliorating the metabolic abnormalities in this particular diabetes model, including insulin resistance and promoting a better long-term glycemic control. (Endocrinology 153: 2178-2188, 2012)

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Asthma is an allergic lung disease can be modulated by drugs that modify the activity of central nervous system (CNS) such as amphetamine (AMPH). AMPH is a highly abused drug that exerts potent effects on behavior and immunity. In this study we investigated the mechanism involved in the effects of long-term AMPH treatment on the increased magnitude of allergic lung response. We evaluated mast cells degranulation, cytokines release, airways responsiveness and, expression of adhesion molecules. Male Wistar rats were treated with AMPH or vehicle (PBS) for 21 days and sensitized with ovalbumin (OVA) one week after the first injection of vehicle or AMPH. Fourteen days after the sensitization, the rats were challenged with an OVA aerosol, and 24 h later their parameters were analyzed. In allergic rats, the treatment with AMPH exacerbated the lung cell recruitment due increased expression of ICAM-1, PECAM-1 and Mac-1 in granulocytes and macrophages recovered from bronchoalveolar lavage. Elevated levels of IL-4, but decreased levels of IL-10 were also found in samples of lung explants after AMPH treatment. Conversely, the ex-vivo tracheal hyper-responsiveness to methacholine (MCh) was reduced by AMPH treatment, whereas the force contraction of tracheal segments due to in vitro antigen challenge remained unaltered. Our findings suggest that lung inflammation and airway hyper-responsiveness due to OVA challenge are under the distinct control of AMPH during long-term treatment. Our data strongly indicate that AMPH positively modulates allergic lung inflammation via the increase of ICAM-1, PECAM-1, Mac-1 and IL-4. AMPH also abrogates the release of the anti-inflammatory cytokine IL-10. (c) 2012 Elsevier B.V. All rights reserved.

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The results of video-assisted thoracic sympathectomy (VATS)in children are unknown. To investigate the improvement in quality of life (QOL) of a group of 45 children who did and did not undergo VATS for the treatment of palmar hyperhidrosis (PH) 4 years after the initial evaluation. Forty-five children with PH were initially evaluated. Children were divided into two groups: 30 in the VATS group and 15 in the control group. We studied the evolution of PH, negative effect of hyperhidrosis on the QOL before the treatment, and improvement in QOL after treatment. Twenty-five patients (83.4%) in the VATS group experienced great improvement in PH, and five (16.6%) experienced partial improvement; 12 (80.0%) children from the control group had some type of improvement, and three (20.0%) had partial improvement. Two (13.3%) children in the control group and 23 (76.7%) in the VATS group had great improvement in QOL. For children with PH and poor QOL, VATS is better than no treatment. It produces better results with regard to sweating and greater improvement in QOL.

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Aims: Development of effective immune-based therapies for patients with non-small-cell lung carcinoma (NSCLC) depends on an accurate characterization of complex interactions that occur between immune cells and the tumour environment. Methods and results: Innate and adaptive immune responses were evaluated in relation to prognosis in 65 patients with surgically excised NSCLC. Immunohistochemistry and morphometry were used to determine the abundance and distribution of immune cells. We found low numbers of immune cells and levels of cytokines in the tumour environment when compared with surrounding parenchyma. Smoking was associated inversely with the adaptive immune response and directly with innate immunity. We observed a prominent adaptive immune response in squamous cell carcinomas (SCC) but greater innate immune responses in adenocarcinomas and large cell carcinomas. Cox model analysis showed a low risk of death for smoking <41 packs/year, N-0 tambour stage, squamous carcinoma, CD4(+) > 16.81% and macrophages/monocytes >4.5%. Collectively, the data indicate that in NSCLC there is not a substantive local immune cell infiltrate within the tumour. Conclusion: Although immune cell infiltration is limited in NSCLC it appears to have an impact on prognosis and this may be of relevance for new immunotherapeutic approaches.

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Introduction. Posttransplant thrombotic microangiopathy (TMA)/hemolytic uremic syndrome (HUS) can occur as a recurrent or de novo disease. Methods. A retrospective single-center observational study was applied in order to examine the incidence and outcomes of de novo TMA/HUS among transplantations performed between 2000 and 2010. Recurrent HUS or antibody-mediated rejections were excluded. Results. Seventeen (1.1%) among 1549 kidney transplant recipients fulfilled criteria for de novo TMA. The mean follow-up was 572 days (range, 69-1769). Maintenance immunosuppression was prednisone, tacrolimus (TAC), and mycophenolic acid in 14 (82%) patients. Mean age at onset was 40 +/- 15 years, and serum creatinine was 6.1 +/- 4.1 mg/dL. TMA occurred at a median of 25 days (range, 1-1755) after transplantation. Nine (53%) patients developed TMA within 1 month of transplantation and only 12% after 1 year. Clinical features were anemia (hemoglobin < 10 g/dL) in 9 (53%) patients, thrombocytopenia in 7 (41%), and increased lactate dehydrogenase in 12 (70%). Decreased haptoglobin was observed in 64% and schistocytes in 35%. Calcineurin inhibitor (CM) withdrawal or reduction was the first step in the management of 10/15 (66%) patients, and 6 (35%) received fresh frozen plasma (FFP) and/or plasmapheresis. TAC was successfully reintroduced in six patients after a median of 17 days. Eight (47%) patients needed dialytic support after TMA diagnosis and 75% remained on dialysis. At 4 years of follow-up, death-censored graft survival was worse for TMA group (43.0% versus 85.6%, log-rank = 0.001; hazard ratio = 3.74) and there was no difference in patient survival (53.1% versus 82.2%, log-rank = 0.24). Conclusion. De novo TMA after kidney transplantation is a rare but severe condition with poor graft outcomes. This syndrome may not be fully manifested, and clinical suspicion is essential for early diagnosis and treatment, based mainly in CM withdrawal and FFP infusions and/or plasmapheresis.

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BACKGROUND: Posttraumatic knee stiffness is a very debilitating condition. Judet's quadricepsplasty technique has been used for more than 50 years. However, few reports of quadricepsplasty results exist in the literature. METHODS: We report the results of 45 cases of posttraumatic arthrofibrosis of the knee treated with Judet's quadricepsplasty. The results of the procedure were analyzed by measuring the degrees of flexion of the operated knees at different time points (before, immediately after, and late postoperatively). RESULTS: The degree of flexion increased from 33.6 degrees (range, 5-80 degrees) preoperatively to 105 degrees (range, 45-160 degrees) immediately after surgery, followed by a slight fall in the range of motion (ROM) in the late postoperative period, which reached an average of 84.8 degrees. There was no significant correlation between knee strength and the patient's gender, but there was a slight trend of lower strength with age. Although Judet's quadricepsplasty technique dates from more than 50 years ago, it still provides good outcomes in the treatment of rigid knees of various etiologies. In general, all cases showed the same pattern of a small decrease in the ROM in the late postoperative period. CONCLUSION: Judet's quadricepsplasty can increase the ROM of rigid knees. The ROM obtained with the surgery persists long term. (J Trauma. 2012; 72: E77-E80. Copyright (C) 2012 by Lippincott Williams & Wilkins)

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Objectives. Adductor spasmodic dysphonia (ADSD) is a focal laryngeal dystonia, which compromises greatly the quality of life of the patients involved. It is a severe vocal disorder characterized by spasms of laryngeal muscles during speech, producing phonatory breaks, forced, strained and strangled voice. Its symptoms result from involuntary and intermittent contractions of thyroarytenoid muscle during speech, which causes vocal fold to strain, pressing each vocal fold against the other and increasing glottic resistance. Botulinum toxin injection remains the gold-standard treatment. However, as injections should be repeated periodically leading to voice quality instability, a more definitive procedure would be desirable. In this pilot study we report the long-term vocal quality results of endoscopic laser thyroarytenoid myoneurectomy. Study Design. Prospective study. Methods. Surgery was performed in 15 patients (11 females and four males), aged between 29 and 73 years, diagnosed with ADSD. Voice Handicap Index (VHI) was obtained before and after surgery (median 31 months postoperatively). Results. A significant improvement in VHI was observed after surgery, as compared with baseline values (P = 0.001). The median and interquartile range for preoperative VHI was 99 and 13, respectively and 24 and 42, for postoperative VHI. Subjective improvement of voice as assessed by the patients showed median improvement of 80%. Conclusions. Because long-term follow-up showed significant improvement of voice quality, this innovative surgical technique seems a satisfactory alternative treatment of ADSD patients who seek a definite improvement of their condition.

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Most of the patients with 5 alpha-RD 2 deficiency are reared in the female social sex due to their severely undervirilized external genitalia but similar to 60% who have not been submitted to orchiectomy in childhood undergo male social sex change at puberty. In our cohort of 30 cases from 18 families, all subjects were registered in the female social sex except for two children-one who had an affected uncle and the other who was diagnosed before being registered. The majority of the patients were satisfied with the long-term results of their treatment and surprisingly, penile length was not associated with satisfactory or unsatisfactory sexual activity. Steroid 5 alpha-RD2 deficiency should be included in the differential diagnosis of all newborns with 46,XY DSD with normal testosterone production before gender assignment or any surgical intervention because these patients should be considered males at birth.

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Assessing the efficacy of implantable cardioverter-defibrillators (ICD) in patients with Chagas' heart disease (ChHD) and identifying the clinical predictors of mortality and ICD shock during long-term follow-up. ChHD is associated with ventricular tachyarrhythmias and an increased risk of sudden cardiac death. Although ChHD is a common form of cardiomyopathy in Latin American ICD users, little is known about its efficacy in the treatment of this population. The study cohort included 116 consecutive patients with ChHD and an ICD implanted for secondary prevention. Of the 116 patients, 83 (72%) were men; the mean age was 54 +/- 10.7 years. Several clinical variables were tested in a multivariate Cox model for predicting long-term mortality. The average follow-up was 45 +/- 32 months. New York Heart Association class I-II developed in 83% of patients. The mean left ventricular ejection fraction was 42 +/- 16% at implantation. Of the 116 patients, 58 (50%) had appropriate shocks and 13 (11%) had inappropriate therapy. A total of 31 patients died (7.1% annual mortality rate). New York Heart Association class III (hazard ratio [HR] 3.09, 95% confidence interval 1.37 to 6.96, p = 0.0064) was a predictor of a worse prognosis. The left ventricular ejection fraction (HR 0.972, 95% confidence interval 0.94 to 0.99, p = 0.0442) and low cumulative right ventricular pacing (HR 0.23, 95% confidence interval 0.11 to 0.49, p = 0.0001) were predictors of better survival. The left ventricular diastolic diameter was an independent predictor of appropriate shock (I-ER 1.032, 95% confidence interval 1.004 to 1.060, p = 0.025). In conclusion, in a long-term follow-up, ICD efficacy for secondary sudden cardiac death prevention in patients with ChHD was marked by a favorable annual rate of all-cause mortality (7.1%); 50% of the cohort received appropriate shock therapy. New York Heart Association class III and left ventricular ejection fraction were independent predictors of worse prognosis, and low cumulative right ventricular pacing defined better survival. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:1040-1045)

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Background and aim of the study: The natriuretic peptides, brain natriuretic peptide (BNP) and its N-terminal prohormone (NT-proBNP), can be used as diagnostic and prognostic markers for aortic stenosis (AS). However, the association between BNP, NT-proBNP, and long-term clinical outcomes in patients with severe AS remains uncertain. Methods: A total of 64 patients with severe AS was prospectively enrolled into the study, and underwent clinical and echocardiographic assessments at baseline. Blood samples were drawn for plasma BNP and NT-proBNP analyses. The primary outcome was death from any cause, through a six-year follow up period. Cox proportional hazards modeling was used to examine the association between natriuretic peptides and long-term mortality, adjusting for important clinical factors. Results: During a mean period of 1,520 681 days, 51 patients (80%) were submitted to aortic valve replacement, and 13 patients (20%) were medically managed without surgical interventions. Mortality rates were 13.7% in the surgical group and 62% in the medically managed group (p <0.001). Patients with higher plasma BNP (>135 pg/ml) and NT-proBNP (>1,150 pg/ml) levels at baseline had a greater risk of long-term mortality (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.1-9.1; HR 4.3, 95% CI 1.4-13.5, respectively). After adjusting for important covariates, both BNP and NT-proBNP remained independently associated with long-term mortality (HR 2.9, 95%CI 1.5-5.7; HR 1.8, 95%CI 1.1-3.1, respectively). Conclusion: In patients with severe AS, plasma BNP and NT-proBNP levels were associated with long-term mortality. The use of these biomarkers to guide treatment might represent an interesting approach that deserves further evaluation. The Journal of Heart Valve Disease 2012;21:331-336

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BACKGROUND: Neoadjuvant chemoradiation (CRT) therapy may result in significant tumor regression in patients with rectal cancer. Patients who develop complete tumor regression have been managed by treatment strategies that are alternatives to standard total mesorectal excision. Therefore, assessment of tumor response with positron emission tomography/computed tomography (PET/CT) after neoadjuvant treatment may offer relevant information for the selection of patients to receive alternative treatment strategies. METHODS: Patients with clinical T2 (cT2) through cT4NxM0 rectal adenocarcinoma were included prospectively. Neoadjuvant therapy consisted of 54 grays of radiation and 5-fluorouracil-based chemotherapy. Baseline PET/CT studies were obtained before CRT followed by PET/CT studies at 6 weeks and 12 weeks after the completion of CRT. Clinical assessment was performed at 12 weeks after CRT completion. PET/CT results were compared with clinical and pathologic data. RESULTS: In total, 99 patients were included in the study. Twenty-three patients were complete responders (16 had a complete clinical response, and 7 had a complete pathologic response). The PET/CT response evaluation at 12 weeks indicated that 18 patients had a complete response, and 81 patients had an incomplete response. There were 5 false-negative and 10 false-positive PET/CT results. PET/CT for the detection of residual cancer had 93% sensitivity, 53% specificity, a 73% negative predictive value, an 87% positive predictive value, and 85% accuracy. Clinical assessment alone resulted in an accuracy of 91%. PET/CT information may have detected misdiagnoses made by clinical assessment alone, improving overall accuracy to 96%. CONCLUSIONS: Assessment of tumor response at 12 weeks after CRT completion with PET/CT imaging may provide a useful additional tool with good overall accuracy for the selection of patients who may avoid unnecessary radical resection after achieving a complete clinical response. Cancer 2012;35013511. (C) 2011 American Cancer Society.

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Background: Recent studies have shown an important reduction of joint overload during locomotion in elderly women with knee osteoarthritis (OA) after short- term use of minimalist shoes. Our aim is to investigate the chronic effect of inexpensive and minimalist footwear on the clinical and functional aspects of OA and gait biomechanics of elderly women with knee OA. Methods/Design: Fifty-six elderly women with knee OA grade 2 or 3 (Kellgren and Lawrence) are randomized into blocks and allocated to either the intervention group, which will use flexible, non-heeled shoes-Moleca (R)-for six months for at least six hours daily, or the control group, which could not use these shoes. Neither group is undergoing physical therapy treatment throughout the intervention period. Moleca (R) is a women's double canvas, flexible, flat walking shoe without heels, with a 5-mm anti-slip rubber sole and a 3-mm internal wedge of ethylene vinyl acetate. Both groups will be followed for six months and will be assessed at baseline condition, after three months, and after six months (end of intervention). All the assessments will be performed by a physiotherapist that is blind to the group allocation. The primary outcome is the pain Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score. The secondary outcomes are global WOMAC score; joint stiffness and disability WOMAC scores; knee pain with a visual analogue scale; walking distance in the six-minute walk test; Lequesne score; amount and frequency (number of days) of paracetamol (500 mg) intake over six months; knee adduction moment during gait; global medical assessment score; and global patient auto-assessment score. At baseline, all patients receive a diary to record the hours of daily use of the footwear intervention; every two weeks, the same physiotherapist makes phone calls to all patients in order to verify adherence to treatment. The statistical analysis will be based on intention to treat analysis, as well as general linear models of analysis of variance for repeated measure to detect treatment-time interactions (alpha = 5%). Discussion: This is the first randomized, clinical trial protocol to assess the chronic effect of minimalist footwear on the clinical and functional aspects and gait biomechanics of elderly women with knee osteoarthritis. We expect that the use of Moleca (R) shoes for six months will provide pain relief, reduction of the knee adduction moment when walking, and improve joint function in elderly women with knee OA, and that the treatment, thus, can be considered another inexpensive and easy-to-use option for conservative OA treatment.

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The continued growth of large cities is producing increasing volumes of urban sewage sludge. Disposing of this waste without damaging the environment requires careful management. The application of large quantities of biosolids (treated sewage sludge) to agricultural lands for many years may result in the excessive accumulation of nutrients like phosphorus (P) and thereby raise risks of eutrophication in nearby water bodies. We evaluated the fractionation of P in samples of an Oxisol collected as part of a field experiment in which biosolids were added at three rates to a maize (Zea mays L) plantation over four consecutive years. The biosolids treatments were equivalent to one, two and four times the recommended N rate for maize crops. In a fourth treatment, mineral fertilizer was applied at the rate recommended for maize. Inorganic P forms were extracted with ammonium chloride to remove soluble and loosely bound P; P bound to aluminum oxide (P-Al) was extracted with ammonium fluoride; P bound to iron oxide (P-Fe) was extracted with sodium hydroxide; and P bound to calcium (P-Ca) was extracted with sulfuric acid. Organic P was calculated as the difference between total P and inorganic P. The predominant fraction of P was P-Fe, followed by P-Al and P-Ca. P fractions were positively correlated to the amounts of P applied, except for P-Ca. The low values of P-Ca were due to the advanced weathering processes to which the Oxisol have been subjected, under which forms of P-Ca are converted to P-Fe and P-Al. The fertilization with P via biosolids increased P availability for maize plants even when a large portion of P was converted to more stable forms. Phosphorus content in maize leaves and grains was positively correlated with P fractions in soils. From these results it can be concluded that the application of biosolids in highly weathered tropical clayey soils for many years, even above the recommended rate based on N requirements for maize, tend to be less potentially hazardous to the environment than in less weathered sandy soils because the non-readily P fractions are predominant after the addition of biosolids. (C) 2012 Elsevier B.V. All rights reserved.