Predictive factors in the long term outcome in gastro-oesophageal reflux disease: six years follow up of 107 patients

There is little information concerning the long term outcome of patients with gastro-oesophageal reflux disease (GORD). Thus 109 patients with reflux symptoms (33 with erosive oesophagitis) with a diagnosis of GORD after clinical evaluation and oesophageal testing were studied. All patients were treated with a stepwise approach: (a) lifestyle changes were suggested aimed at reducing reflux and antacids and the prokinetic agent domperidone were prescribed; (b) H2 blockers were added after two months when symptoms persisted; (c) anti-reflux surgery was indicated when there was no response to (b). Treatment was adjusted to maintain clinical remission during follow up. Long term treatment need was defined as minor when conservative measures sufficed for proper control, and as major if daily H2 blockers or surgery were required. The results showed that one third of the patients each had initial therapeutic need (a), (b), and (c). Of 103 patients available for follow up at three years and 89 at six years, respective therapeutic needs were minor in 52% and 55% and major in 48% and 45%. Eighty per cent of patients in (a), 67% in (b), and 17% in (c) required only conservative measures at six years. A decreasing lower oesophageal sphincter pressure (p < 0.001), radiological reflux (p = 0.028), and erosive oesophagitis (p = 0.031), but not initial clinical scores, were independent predictors of major therapeutic need as shown by multivariate analysis. The long term outcome of GORD is better than previously perceived.

Association of ischaemic stroke subtype with long-term cardiovascular events.

BACKGROUND AND PURPOSE: There is no strong evidence that all ischaemic stroke types are associated with high cardiovascular risk. Our aim was to investigate whether all ischaemic stroke types are associated with high cardiovascular risk. METHODS: All consecutive patients with ischaemic stroke registered in the Athens Stroke Registry between 1 January 1993 and 31 December 2010 were categorized according to the TOAST classification and were followed up for up to 10 years. Outcomes assessed were cardiovascular and all-cause mortality, myocardial infarction, stroke recurrence, and a composite cardiovascular outcome consisting of myocardial infarction, angina pectoris, acute heart failure, sudden cardiac death, stroke recurrence and aortic aneurysm rupture. The Kaplan-Meier product limit method was used to estimate the probability of each end-point in each patient group. Cox proportional hazards models were used to determine the independent covariates of each end-point. RESULTS: Two thousand seven hundred and thirty patients were followed up for 48.1 ± 41.9 months. The cumulative probabilities of 10-year cardiovascular mortality in patients with cardioembolic stroke [46.6%, 95% confidence interval (CI) 40.6-52.8], lacunar stroke (22.1%, 95% CI 16.2-28.0) or undetermined stroke (35.2%, 95% CI 27.8-42.6) were either similar to or higher than those of patients with large-artery atherosclerotic stroke (LAA) (28.7%, 95% CI 22.4-35.0). Compared with LAA, all other TOAST types had a higher probability of 10-year stroke recurrence. In Cox proportional hazards analysis, compared with patients with LAA, patients with any other stroke type were associated with similar or higher risk for the outcomes of overall mortality, cardiovascular mortality, stroke recurrence and composite cardiovascular outcome. CONCLUSIONS: Large-artery atherosclerotic stroke and cardioembolic stroke are associated with the highest risk for future cardiovascular events, with the latter carrying at least as high a risk as LAA stroke.

Résultats anatomiques comparés à long terme de décollements de rétine avec prolifération vitréo-rétinienne opérés avec ou sans utilisation de perfluorocarbones liquides [Long-term comparative anatomic results of retinal detachment with vitreoretinal proliferation operated with or without using liquid perfluorocarbons].

PURPOSE: To investigate whether peroperative perfluorocarbon liquids (PFCL) improve the long term anatomical success of retinal detachment associated with severe proliferative vitreoretinopathy (PVR). PATIENTS AND METHODS: The charts of 62 successive patients operated on for retinal detachment associated with severe PVR were retrospectively analyzed. For one group of 39 patients PFCL were used intraoperatively to improve membrane dissection. The anatomical status of the two groups were compared one month after surgery and at least 6 months after silicone oil ablation. RESULTS: Anatomical success was observed in 84.6% in the group of patients operated with PFCL compared to 52% in the other group (P = 0.005). At the end of the follow up, anatomical success was observed in 64% of patients operated with PFCL compared to 61% in the control group (P = 0.8). However, recurrences were observed later in the group operated on with PFCL. CONCLUSION: Perfluorocarbons liquids significantly improve the initial reattachment of retinal detachment complicated with severe PVR, but they do not seem to improve their final anatomical status.

Endoscopic and surgical treatment of vesico-ureteral reflux in children. Comparative long-term follow-up.

PRINCIPLES: This retrospective study analyzes the long-term results of endoscopic and surgical treatment of vesico-ureteral reflux in children. METHODS: A cohort of 130 patients, 67 girls and 63 boys with a mean age of 30 months were treated either by endoscopic subureteral collagen injection (SCIN) in 92 and by Cohen reimplantation surgery in 123 refluxing ureteral units. Mean follow-up was 4.2 years varying from 1 to 8.7 years. Reflux recurrence, urinary tract infection (UTI) and renal function were evaluated. RESULTS: After SCIN reflux was absent in 64% at 6 months. 20% of the initially 92 refluxing ureters were injected twice. After one or two injections reflux was absent in 71%. In 21% recurrent reflux was of grade I or II, not requiring further treatment. UTI was observed in 27%. After Cohen ureteral reimplantation reflux was absent in 96% at 6 months. UTI was observed in 23%. Renal function at diagnosis and follow-up was compared in children with bilateral grade III reflux only. In patients treated with SCIN it was normal in 77% preoperatively and in 90% at follow-up. In patients treated by open surgery it was normal in 47% preoperatively and in 76% at follow-up. CONCLUSION: For high-grade vesico-ureteral reflux re-implantation surgery remains the gold standard. SCIN is indicated for low and medium grade reflux. Recurrent bacteriuria was observed more often after SCIN and pyelonephritis more often after open surgery. The renal function seems to be preserved with both techniques.

TORC1 is a calcium- and cAMP-sensitive coincidence detector involved in hippocampal long-term synaptic plasticity.

A key feature of memory processes is to link different input signals by association and to preserve this coupling at the level of synaptic connections. Late-phase long-term potentiation (L-LTP), a form of synaptic plasticity thought to encode long-term memory, requires gene transcription and protein synthesis. In this study, we report that a recently cloned coactivator of cAMP-response element-binding protein (CREB), called transducer of regulated CREB activity 1 (TORC1), contributes to this process by sensing the coincidence of calcium and cAMP signals in neurons and by converting it into a transcriptional response that leads to the synthesis of factors required for enhanced synaptic transmission. We provide evidence that TORC1 is involved in L-LTP maintenance at the Schaffer collateral-CA1 synapses in the hippocampus.

Single Point of Entry Long-Term Living Resource System Team Report

Pursuant to House File 451 the Single Point of Entry Long-Term Living Resources System Team, involving several state agencies as well as interested associations, submitted a report to the legislature on recommendations to establish a single point of entry system.

Heterologous prime-boost regimen adenovector 35-circumsporozoite protein vaccine/recombinant Bacillus Calmette-Guérin expressing the Plasmodium falciparum circumsporozoite induces enhanced long-term memory immunity in BALB/c mice.

BACKGROUND: Sustained antibody levels are a hallmark of immunity against many pathogens, and induction of long-term durable antibody titers is an essential feature of effective vaccines. Heterologous prime-boost approaches with vectors are optimal strategies to improve a broad and prolonged immunogenicity of malaria vaccines. RESULTS: In this study, we demonstrate that the heterologous prime-boost regimen Ad35-CS/BCG-CS induces stronger immune responses by enhancing type 1 cellular producing-cells with high levels of CSp-specific IFN-γ and cytophilic IgG2a antibodies as compared to a homologous BCG-CS and a heterologous BCG-CS/CSp prime-boost regimen. Moreover, the heterologous prime-boost regimen elicits the highest level of LLPC-mediated immune responses. CONCLUSION: The increased IFN-γ-producing cell responses induced by the combination of Ad35-CS/BCG-CS and sustained type 1 antibody profile together with high levels of LLPCs may be essential for the development of long-term protective immunity against liver-stage parasites.

Effect of long-term climbing training on cerebellar ataxia: a case series.

Background. Efficient therapy for both limb and gait ataxia is required. Climbing, a complex task for the whole motor system involving balance, body stabilization, and the simultaneous coordination of all 4 limbs, may have therapeutic potential. Objective. To investigate whether long-term climbing training improves motor function in patients with cerebellar ataxia. Methods. Four patients suffering from limb and gait ataxia underwent a 6-week climbing training. Its effect on ataxia was evaluated with validated clinical balance and manual dexterity tests and with a kinematic analysis of multijoint arm and leg pointing movements. Results. The patients increased their movement velocity and achieved a more symmetric movement speed profile in both arm and leg pointing movements. Furthermore, the 2 patients who suffered the most from gait ataxia improved their balance and 2 of the 4 patients improved manual dexterity. Conclusion. Climbing training has the potential to serve as a new rehabilitation method for patients with upper and lower limb ataxia.

Agglomeration and labour productivity in Spanish industry: a long-term analysis

This paper analyzes the relationship between spatial density of economic activity and interregional differences in the productivity of industrial labour in Spain during the period 1860-1999. In the spirit of Ciccone and Hall (1996) and Ciccone (2002), we analyze the evolution of this relationship over the long term in Spain. Using data on the period 1860-1999 we show the existence of an agglomeration effect linking the density of economic activity with labour productivity in the industry. This effect was present since the beginning of the industrialization process in the middle of the 19th century but has been decreasing over time. The estimated elasticity of labour productivity with respect to employment density was close to 8% in the subperiod 1860-1900, reduces to a value of around 7% in the subperiod 1914-1930, to 4% in the subperiod 1965-1979 and becomes insignificant in the final subperiod 1985-1999. At the end of the period analyzed there is no evidence of the existence of net agglomeration effects in the industry. This result could be explained by an important increase in the congestion effects in large industrial metropolitan areas that would have compensated the centripetal or agglomeration forces at work. Furthermore, this result is also consistent with the evidence of a dispersion of industrial activity in Spain during the last decades.

Radioimmunotherapy combined with maintenance anti-CD20 antibody may trigger long-term protective T cell immunity in follicular lymphoma patients.

Growing evidence suggests that the patient's immune response may play a major role in the long-term efficacy of antibody therapies of follicular lymphoma (FL). Particular long-lasting recurrence free survivals have been observed after first line, single agent rituximab or after radioimmunotherapy (RIT). Rituximab maintenance, furthermore, has a major efficacy in prolonging recurrence free survival after chemotherapy. On the other hand, RIT as a single step treatment showed a remarkable capacity to induce complete and partial remissions when applied in recurrence and as initial treatment of FL or given for consolidation. These clinical results strongly suggest that RIT combined with rituximab maintenance could stabilize the high percentages of patients with CR and PR induced by RIT. While the precise mechanisms of the long-term efficacy of these 2 treatments are not elucidated, different observations suggest that the patient's T cell immune response could be decisive. With this review, we discuss the potential role of the patient's immune system under rituximab and RIT and argue that the T cell immunity might be particularly promoted when combining the 2 antibody treatments in the early therapy of FL.

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.

Inhibition of glucose-induced insulin secretion by long-term preexposure of pancreatic islets to leptin.

Here we evaluated the effect of leptin on glucose-induced insulin secretion by normal rat pancreatic islets. We show in perifusion experiments that leptin had no acute effect on the secretory activity of beta-cells. However, following preexposure to leptin a pronounced time- and dose-dependent inhibition of both first and second phases of secretion was observed. Maximum inhibition was obtained at 24 h and with 100 nM leptin. This inhibition did not involve a decrease in cellular insulin content. It was also not observed with islets from fa/fa rats. Leptin thus inhibits insulin secretion by a mechanism which requires long-term preexposure to the hormone and which may involve alteration in beta-cell gene expression.

Isolated limb perfusion with tumor necrosis factor and melphalan for non-resectable soft tissue sarcomas: long-term results on efficacy and limb salvage in a selected group of patients

Background And Objectives: Isolated limb perfusion with TNF-alpha and melphalan (TM-ILP) is a limb salvage therapy for non-resectable soft tissue sarcomas (STS) of the extremities. It is indicated for patients for whom amputation or debilitating surgery is the only alternative. It can be used either as an exclusive therapy (in palliation) or as a neo-adjuvant treatment, followed by marginal resection of tumor remnants with minimal functional impairment. Methods: Between February 1992 and March 2006, 57 TM-ILPs were performed on 51 patients with 88% high grade and 84% advanced stage tumors. Results: Mean follow-up is 38.9 months (4-159, median 22 months). Twenty-one percent patients had significant early complications, with 3 major re-operations, and 23% suffered long-lasting complications. Complete response was observed in 25%, partial response in 42%, stable disease in 14% and progressive disease in 14%. Resection of the tumor remnants was possible in 65%. A complementary treatment was necessary in 31%, mostly radiation therapy. A local recurrence was observed in 35%, after a mean of 20.3 months (2-78), and distant relapse was seen in 45%, after a mean of 13.4 months (5-196). Mean Disease-free survival was 14.9 months, and overall 5-year-survival 43.5%. Amputation rate at 5 years was 24%. Conclusions: TM-ILP is a conservative treatment with a high complications rate, but it can be successful even for the most severe STS of extremities. As a consequence the limb can be spared from amputation or debilitating surgery on the long term in about 75% of patients