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Terms modified by Uncontrolled Selected AbstractsNitroxide-Mediated Polymerization of Methyl Methacrylate Using an SG1-Based Alkoxyamine: How the Penultimate Effect Could Lead to Uncontrolled and Unliving PolymerizationMACROMOLECULAR CHEMISTRY AND PHYSICS, Issue 14 2006Yohann Guillaneuf Abstract Summary: The nitroxide-mediated polymerization (NMP) of MMA initiated with a new crowded SG1-based alkoxyamine was performed. Contrary to the results expected after a kinetic analysis (Fischer's diagram), the polymerization of MMA at 45,°C with SG1 showed only partial control and livingness during the first 15% of conversion. Simulations using PREDICI highlighted that the kinetic rate constants currently in use had not been correctly estimated and that a strong penultimate effect drastically increased the equilibrium constant K (7,×,10,7), preventing a well-controlled polymerization. Experimental determination of the kc value (1.4,×,104 L,·,mol,1,·,s,1) confirmed a strong penultimate effect on the recombination reaction, whereas for the dissociation reaction this effect is lower (kd,=,10,2,·,s,1). Nitroxide-mediated polymerization of MMA at 45,°C initiated with a new crowded SG1-based alkoxyamine. [source] Attitudes of the American Public toward Organ Donation after Uncontrolled (Sudden) Cardiac DeathAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010M. L. Volk Concerns about public support for organ donation after cardiac death have hindered expansion of this practice, particularly rapid organ recovery in the context of uncontrolled (sudden) cardiac death (uDCD). A nationally representative Internet-based panel was provided scenarios describing donation in the context of brain death, controlled cardiac death and uncontrolled cardiac death. Participants were randomized to receive questions about trust in the medical system before or after the rapid organ recovery scenario. Among 1631 panelists, 1049 (64%) completed the survey. Participants expressed slightly more willingness to donate in the context of controlled and uncontrolled cardiac death than after brain death (70% and 69% vs. 66%, respectively, p < 0.01). Eighty percent of subjects (95% CI 77,84%) would support having a rapid organ recovery program in their community, though 83% would require family consent or a signed donor card prior to invasive procedures for organ preservation. The idea of uDCD slightly decreased trust in the medical system from 59% expressing trust to 51% (p = 0.02), but did not increase belief that a signed donor card would interfere with medical care (28% vs. 32%, p = 0.37). These findings provide support for the careful expansion of uDCD, albeit with formal consent prior to organ preservation. [source] The effectiveness of psychological treatments for treatment-resistant depression: a systematic reviewACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2005S. McPherson Objective:, A systematic review of all studies (controlled and uncontrolled) to evaluate psychological interventions with treatment-resistant depression. Method:, A systematic search to identify studies evaluating a psychological intervention with adults with a diagnosis of major depressive disorder who had not responded to at least one course of antidepressant medication. Results:, Twelve studies met inclusion criteria, of which four were controlled and eight uncontrolled. Treatment effect sizes were computable for four studies and ranged from 1.23 to 3.10 with a number of better quality studies demonstrating some improvements in patients following a psychological intervention. Conclusion:, Psychological treatments for depression are commonly delivered and often recommended following the failure of medication. The paucity of evidence for their effectiveness in these situations is a significant problem. There is a need for studies with a strong controlled design investigating the effectiveness of psychological treatments for patients with treatment-resistant depression. [source] Earlier triple therapy with pioglitazone in patients with type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 9 2009G. Charpentier Aims: This study assessed the efficacy of add-on pioglitazone vs. placebo in patients with type 2 diabetes uncontrolled by metformin and a sulphonylurea or a glinide. Methods: This multicentre, double-blind, parallel-group study randomized 299 patients with type 2 diabetes to receive 30 mg/day pioglitazone or placebo for 3 months. After this time, patients continued with pioglitazone, either 30 mg [if glycated haemoglobin A1c (HbA1c) ,6.5%] or titrated up to 45 mg (if HbA1c >6.5%), or placebo for a further 4 months. The primary efficacy end-point was improvement in HbA1c (per cent change). Secondary end-points included changes in fasting plasma glucose (FPG), insulin, C-peptide, proinsulin and lipids. The proinsulin/insulin ratio and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ,-cell function (HOMA-B) were calculated. Results: Pioglitazone add-on therapy to failing metformin and sulphonylurea or glinide combination therapy showed statistically more significant glycaemic control than placebo addition. The between-group difference after 7 months of triple therapy was 1.18% in HbA1c and ,2.56 mmol/l for FPG (p < 0.001). Almost half (44.4%) of the patients in the pioglitazone group who had a baseline HbA1c level of <8.5% achieved the HbA1c target of < 7.0% by final visit compared with 4.9% in the placebo group. When the baseline HbA1c level was , 8.5%, 13% achieved the HbA1c target of < 7.0% in the pioglitazone group and none in the placebo group. HOMA-IR, insulin, proinsulin and C-peptide decreased and HOMA-B increased in the pioglitazone group relative to the placebo group. Conclusions: In patients who were not well controlled with dual combination therapy, the early addition of pioglitazone improved HbA1c, FPG and surrogate measures of ,-cell function. Patients were more likely to reach target HbA1c levels (< 7.0%) with pioglitazone treatment if their baseline HbA1c levels were < 8.5%, highlighting the importance of early triple therapy. [source] The effectiveness of footwear and offloading interventions to prevent and heal foot ulcers and reduce plantar pressure in diabetes: a systematic reviewDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S1 2008S. A. Bus Abstract Background Footwear and offloading techniques are commonly used in clinical practice for the prevention and treatment of foot ulcers in diabetes, but the evidence base to support this use is not well known. The goal of this review was to systematically assess the literature and to determine the available evidence on the use of footwear and offloading interventions for ulcer prevention, ulcer treatment, and plantar pressure reduction in the diabetic foot. Methods A search was made for reports on the effectiveness of footwear and offloading interventions in preventing or healing foot ulcers or reducing plantar foot pressure in diabetic patients published prior to May 2006. Both controlled and uncontrolled studies were included. Assessment of the methodological quality of studies and data extraction was independently performed by two reviewers. Interventions were assigned into four subcategories: casting, footwear, surgical offloading and other offloading techniques. Results Of 1651 articles identified in the baseline search, 21 controlled studies were selected for grading following full text review. Another 108 uncontrolled and cross-sectional studies were examined. The evidence to support the use of footwear and surgical interventions for the prevention of ulceration is meagre. Evidence was found to support the use of total contact casts and other non-removable modalities for treatment of neuropathic plantar ulcers. More studies are needed to support the use of surgical offloading techniques for ulcer healing. Plantar pressure reduction can be achieved by several modalities including casts, walkers, and therapeutic footwear, but the diversity in methods and materials used limits the comparison of study results. Conclusions This systematic review provides support for the use of non-removable devices for healing plantar foot ulcers. Furthermore, more high-quality studies are urgently needed to confirm the promising effects found in both controlled and uncontrolled studies of footwear and offloading interventions designed to prevent ulcers, heal ulcers, or reduce plantar pressure. Copyright © 2008 John Wiley & Sons, Ltd. [source] Social consumption of alcohol in adolescents with Type 1 diabetes is associated with increased glucose lability, but not hypoglycaemiaDIABETIC MEDICINE, Issue 8 2006D. Ismail Abstract Aims To determine the effects of social consumption of alcohol by diabetic adolescents on glycaemic control. Methods Fourteen (five male) patients aged > 16 years were recruited from the diabetes clinic at the Royal Children's Hospital. The continuous glucose monitoring system (CGMS) was attached at a weekend when alcohol consumption was planned for one night only. For each patient, the 12-h period from 18.00 h to 06.00 h for the night with alcohol consumption (study period) was compared with the same period with non-alcohol consumption (control period) either 24 h before or after the alcohol study night. Thus, each subject was his/her own control. Glycaemic outcomes calculated from continuous glucose monitoring included mean blood glucose (MBG), percentage of time spent at low glucose levels (CGMS < 4.0 mmol/l), normal glucose levels (CGMS 4.0,10.0 mmol/l) and high glucose levels (> 10.0 mmol/l) and continuous overall net glycaemic action (CONGA). Results The mean number of standard alcohol drinks consumed during the study period was 9.0 for males and 6.3 for females. There was no difference in percentage of time at high and normal glucose levels in the study and control periods. During the control period, there was a higher percentage of time with low glucose levels compared with the study period (P < 0.05). There was an increased level of glycaemic variation during the study time when compared with the control period. Conclusions In an uncontrolled, social context, moderately heavy alcohol consumption by adolescents with Type 1 diabetes appears to be associated with increased glycaemic variation, but not with low glucose levels. [source] Insulin pump therapy vs. multiple daily injections in obese Type 2 diabetic patientsDIABETIC MEDICINE, Issue 8 2005J. Wainstein Abstract Aims To compare the efficacy of insulin pump treatment with multiple daily injections in the treatment of poorly controlled obese Type 2 diabetic patients already receiving two or more daily injections of insulin plus metformin. Methods Forty obese Type 2 diabetic subjects (using insulin) were randomized to treatment with continuous subcutaneous infusion pump (CSII) (Minimed®) or multiple daily insulin injections (MDI). At the end of the first 18-week treatment period, patients underwent a 12-week washout period during which they were treated with MDI plus metformin. They were then crossed-over to the other treatment for an 18-week follow-up period. Patients performed 4-point daily self blood-glucose monitoring (SBGM) on a regular basis and 7-point monitoring prior to visits 2, 8, 10 and 16. A subset of patients underwent continuous glucose monitoring using the Minimed® continuous glucose monitoring system (CGMS) at visits 2, 8, 10 and 16. A standard meal test was performed in which serum glucose was tested at fasting and once each hour for 6 h following a test meal. Glucose levels were plotted against time and the area under the curve (AUC) was calculated. HbA1c, weight, daily insulin dose and hypoglycaemic episodes were recorded. Results In obese Type 2 diabetic patients already treated with insulin, treatment with CSII significantly reduced HbA1c levels compared with treatment with MDI. An additional CSII treatment benefit was demonstrated by reduced meal-test glucose AUC. Initial reduction of daily insulin requirement observed in CSII-treated subjects during the first treatment period was attributable to a period effect and did not persist over time. Conclusions In the intent-to-treat analysis, CSII appeared to be superior to MDI in reducing HbA1c and glucose AUC values without significant change in weight or insulin dose in obese, uncontrolled, insulin-treated Type 2 diabetic subjects. [source] Carisbamate as adjunctive treatment of partial onset seizures in adults in two randomized, placebo-controlled trialsEPILEPSIA, Issue 3 2010Michael R. Sperling Summary Purpose:, To assess the efficacy, safety, and tolerability of the investigational drug carisbamate as adjunctive treatment for partial-onset seizures (POS). Methods:, Two identical, randomized, placebo-controlled, double-blind studies were conducted in adults with POS uncontrolled for ,1 year. Therapy-refractory epilepsy patients (,16 years) remained on stable doses of prescribed antiepileptic drugs (,2) for an 8-week prospective baseline phase and were then randomized (1:1:1) to carisbamate 200 mg/day, carisbamate 400 mg/day, or placebo, for a 12-week double-blind phase. Primary efficacy end points were percent reduction in seizure frequency and responder rate (patients with ,50% reduction in POS frequency) during the double-blind phase compared with the prospective baseline phase. Results:, Of the 565 patients randomized in study 1, 93% completed the study; of the 562 randomized in study 2, 94% completed the study. Patient characteristics were similar across both studies and treatment arms: mean age, 35 years (study 1, range 16,75 years) and 36 years (study 2, range 16,74 years); approximately 50% were men. Treatment with carisbamate 400 mg/day resulted in significant improvement (p < 0.01) in both efficacy measures compared with placebo in study 1 but not in study 2. Carisbamate 200 mg/day did not differ statistically from placebo in either study. Among the most common treatment-emergent adverse events (,5% in any group), those with an incidence exceeding placebo (,3%) were dizziness (400 mg/day group) and somnolence. Conclusions:, Carisbamate 400 mg/day was effective in patients with refractory partial-onset seizures in one of these global studies. More than 200 mg/day of carisbamate is required for efficacy. Carisbamate was well-tolerated in both studies. [source] Changes in Cerebral Blood Flow During and After 48 H of Both Isocapnic and Poikilocapnic Hypoxia in HumansEXPERIMENTAL PHYSIOLOGY, Issue 5 2002Marc J. Poulin During acclimatization to the hypoxia of altitude, the cerebral circulation is exposed to arterial hypoxia and hypocapnia, two stimuli with opposing influences on cerebral blood flow (CBF). In order to understand the resultant changes in CBF, this study examined the responses of CBF during a period of constant mild hypoxia both with and without concomitant regulation of arterial PCO2. Nine subjects were each exposed to two protocols in a purpose-built chamber: (1) 48 h of isocapnic hypoxia (Protocol I), where end-tidal PO2 (PET,O2) was held at 60 Torr and end-tidal PCO2 (PET,CO2) at the subject's resting value prior to experimentation; and (2) 48 h of poikilocapnic hypoxia (Protocol P), where PET,O2 was held at 60 Torr and PET,CO2 was uncontrolled. Transcranial Doppler ultrasound was used to assess CBF. At 24 h intervals during and after the hypoxic exposure CBF was measured and the sensitivity of CBF to acute variations in PO2 and PCO2 was determined. During Protocol P, PET,CO2 decreased by 13% (P < 0.001) and CBF decreased by 6% (P < 0.05), whereas during Protocol I, PET,CO2 and CBF remained unchanged. The sensitivity of CBF to acute variations in PO2 and PCO2 increased by 103% (P < 0.001) and 28% (P < 0.01), respectively, over the 48 h period of hypoxia. These changes did not differ between protocols. In conclusion, CBF decreases during mild poikilocapnic hypoxia, indicating that there is a predominant effect on CBF of the associated arterial hypocapnia. This fall occurs despite increases in the sensitivity of CBF to acute variations in PO2/PCO2 arising directly from the hypoxic exposure. [source] Guided self-help supported by paraprofessional mental health workers: an uncontrolled before,after cohort studyHEALTH & SOCIAL CARE IN THE COMMUNITY, Issue 1 2009Paul Farrand Senior Lecturer in Health Psychology Abstract There has been considerable development of guided self-help clinics within primary care. This uncontrolled before,after cohort study examines efficiency and effectiveness of these clinics when supported by paraprofessional mental health workers having little mental health training and experience. Data were collected by seven Graduate Mental Health Workers (GMHW) located in South-west England. Alongside an analysis of clinic attendance and dropout, efficiency was measured with respect to the number and length of sessions to support patients with the effectiveness of the interventions examined with respect to problem severity. Over a 15-month period, 1162 patients were referred to the GMHW clinics with 658 adopting guided self-help. Patients using guided self-help received an average input per patient, excluding assessment, of four sessions of 40 minutes. Dropout rate was comparable to other primary-care-based mental health clinics supported by experienced mental health professionals with 458 patients completing all support sessions. However, only 233 patients went on to attend the 3 months of follow-up session. Effectiveness of guided self-help clinics supported by paraprofessional mental health workers was comparable to that supported by an experienced mental health nurse. Improvements in problem severity were statistically significant, with 55% and 58% (final support session) and 63% and 62% (3 months of follow-up) of patients experiencing clinically significant and reliable change for anxiety and depression, respectively. However, concerns exist over the efficiency of the GMHW clinic especially with respect to the use of longer support sessions and high dropout rate at the 3 months of follow-up session. The paper concludes by highlighting the effectiveness of guided self-help when supported by paraprofessional mental health workers, but questions the utility of the two-plus-one model of service delivery proposing a collaborative care approach as an alternative. [source] Therapy of acute hepatitis CHEPATOLOGY, Issue S1 2002Professor Alfredo Alberti M.D. Acute hepatitis C has a high propensity to become chronic, which provides the rationale for treating patients with acute disease attempting to prevent chronicity. Almost all published studies on therapy of acute hepatitis C have been small in size, uncontrolled, and highly heterogeneous as to patient features, dose and duration of treatment, follow-up evaluation, and criteria used to define efficacy and safety. The published studies on treatment of acute hepatitis C have used standard alfa or beta interferon monotherapy: none have evaluated combination therapy of interferon and ribavirin or peginterferon. Several meta-analyses of published studies have concluded that initiation of interferon monotherapy during the acute phase of hepatitis C virus (HCV) infection significantly reduces (by 30% to 40%) evolution to chronic hepatitis. The tolerability of interferon in acute hepatitis C has been excellent, even in symptomatic and icteric patients; the side effects and adverse events being similar in type and frequency to those seen when treating chronic cases. Thus, currently available data support treatment of patients with acute hepatitis C, but data are insufficient to draw firm conclusions about which patients to treat, when therapy should be started, or what regimen is optimal. Future studies of adequate size and design should focus on efficacy and tolerability of peginterferons and whether therapy should be started immediately after diagnosis or delayed for 2 to 4 months to avoid treatment of patients who spontaneously recover. (HEPATOLOGY 2002;36:S195-S200). [source] TIPS is a useful long-term derivative therapy for patients with Budd-Chiari syndrome uncontrolled by medical therapyHEPATOLOGY, Issue 1 2002Antonia Perelló Patients with Budd-Chiari syndrome (BCS) may require treatment with portal decompressive surgery or liver transplantation. Transjugular intrahepatic portosystemic shunt (TIPS) represents a new treatment alternative, but its long-term effect on BCS outcome has not been evaluated. Twenty-one patients with BCS consecutively admitted to our unit were evaluated. The mean follow-up was 4 ± 3 years. Seven patients had nonprogressive forms and were successfully controlled with medical therapy; 1 case, with a short-length hepatic vein stenosis was successfully treated by angioplasty. All 8 patients are alive and asymptomatic. The remaining 13 patients, had a TIPS because of clinical deterioration (in one of them, because early TIPS thrombosis a successful side-to-side portacaval shunt [SSPCS] was performed) followed by an improvement in clinical condition. However, a patient with fulminant liver failure before TIPS insertion, died 4 months later and another patient with cirrhosis at diagnosis had liver transplantation 2 years later. The remaining 11 patients are alive and free of ascites. In 3 of these patients TIPS is patent after 3, 6, and 12 months. The remaining 8 patients developed late TIPS dysfunction. In two of these cases, after angioplasty and restenting, TIPS is patent after a follow-up of 9 and 80 months. In 5 other patients, recurring TIPS occlusion was not further corrected because no signs of portal hypertension were present. In conclusion, in patients with BCS uncontrolled with medical therapy, TIPS is a highly effective technique that is associated with long-term survival. [source] Functional brain mapping during free viewing of natural scenesHUMAN BRAIN MAPPING, Issue 2 2004Andreas Bartels Abstract Previous imaging studies have used mostly perceptually abstracted, idealized, or static stimuli to show segregation of function in the cerebral cortex. We wanted to learn whether functional segregation is maintained during more natural, complex, and dynamic conditions when many features have to be processed simultaneously, and identify regions whose activity correlates with the perception of specific features. To achieve this, we used functional magnetic resonance imaging (fMRI) to measure brain activity when human observers viewed freely dynamic natural scenes (a James Bond movie). The intensity with which they perceived different features (color, faces, language, and human bodies) was assessed psychometrically in separate sessions. In all subjects different features were perceived with a high degree of independence over time. We found that the perception of each feature correlated with activity in separate, specialized areas whose activity also varied independently. We conclude that even in natural conditions, when many features have to be processed simultaneously, functional specialization is preserved. Our method thus opens a new way of brain mapping, which allows the localization of a multitude of brain areas based on a single experiment using uncontrolled, natural stimuli. Furthermore, our results show that the intensity of activity in a specialized area is linearly correlated with the intensity of its perceptual experience. This leads us to suggest that each specialized area is directly responsible for the creation of a feature-specific conscious percept (a microconsciousness). Hum. Brain Mapp. 21:75,83, 2004. © 2003 Wiley-Liss, Inc. [source] Efficacy of methotrexate in ulcerative colitis: Failure or promiseINFLAMMATORY BOWEL DISEASES, Issue 8 2010Hans H. Herfarth MD Abstract Background: Low-dose methotrexate is a widely used and efficacious therapy in chronic inflammatory disorders such as psoriasis and rheumatoid arthritis. Prospective randomized controlled trials have demonstrated the efficacy of parenteral methotrexate in Crohn's disease (CD). We performed a systematic review of the efficacy of methotrexate in ulcerative colitis (UC) and discuss the results in the context of the known pharmacokinetics and adverse events of methotrexate therapy in inflammatory bowel diseases and other inflammatory conditions. Materials and Methods: We performed a systematic review of the literature in Medline, Embase, and Web of Science. All publications describing patients with UC treated with methotrexate were included. Results: We identified 12 studies or retrospective case series and 5 meeting abstracts that met the inclusion criteria. Only 1 study reported a prospective randomized placebo-controlled trial using methotrexate at a dose of 12.5 mg orally with no significant clinical benefit. However, the majority of uncontrolled retrospective analyses suggest a clinical response to methotrexate therapy in a range of 30%,80% when the drug is applied by parenteral route in doses between 20,25 mg. Conclusions: The only randomized controlled trial of methotrexate in UC employed oral dosing and doses lower than those shown to be effective in CD and did not demonstrate efficacy, whereas uncontrolled, retrospective studies using doses and routes of administration similar to those employed in CD suggest benefit. Well-designed, prospective, placebo-controlled trials of methotrexate in UC are needed. Inflamm Bowel Dis 2010 [source] Long-term oral tacrolimus therapy in refractory to infliximab fistulizing Crohn's disease.INFLAMMATORY BOWEL DISEASES, Issue 1 2005A Pilot Study Abstract Aims: To evaluate efficacy and safety of oral tacrolimus in cases of fistulizing Crohn's disease (FCD), which is refractory to conventional therapy including infliximab. Methods: Patients with fistulas, previously and unsuccessfully treated with all conventional therapy (i.e., antibiotics, azathioprine, or 6-mercaptopurine and infliximab), were enrolled in a prospective, uncontrolled, open-label study of long-term treatment with oral tacrolimus (0.05 mg/kg every12 h). The evaluation of the clinical response was complemented by use of the perianal Crohn's disease activity index (PCDAI) and magnetic resonance imaging-based score (MRS) with determined periodicity. Results: Ten patients were included in the study (enterocutaneous fistula, 3 patients; perianal fistula, 4 patients; rectovaginal fistula, 3 patients) with 6 to 24 months of follow-up. Five patients were steroid-dependent, and 4 patients needed maintenance treatment with immunosuppressant agents. Four patients (40%) achieved complete clinical responses, which were verified by PCDAI and MRS. Five patients (50%) achieved partial responses (i.e., important decreases in fistula drainage, size, discomfort, and PCDAI/MRS values). Decreases in both the PCDAI and MRS were statistically significant (P < 0.05). All steroid-dependent patients stopped therapy with prednisone, and concomitant immunosuppressive therapy was tapered. The response was maintained, and no new flare-up of the disease was observed. Only mild adverse events were detected (1 patient withdrew from treatment due to headache), and no case of nephrotoxicity or diabetes was detected. One patient had received no benefit from therapy after 6 months. Conclusions: Oral tacrolimus could be an effective and safe treatment for patients with FCD, even if there has been no response to infliximab treatment. Randomized studies are needed to compare oral tacrolimus with infliximab in terms of efficacy, safety, and costs. [source] Zoledronic acid prevents bone loss after allogeneic haemopoietic stem cell transplantationINTERNAL MEDICINE JOURNAL, Issue 9 2006A. B. D'Souza Abstract Allogeneic haemopoietic stem cell transplant (alloHSCT) patients are at increased risk of osteoporosis. Zoledronic acid (ZA) is a potent i.v. bisphosphonate; however, there are few data on ZA use after alloHSCT. The aim of this study is to examine the effect of a single 4 mg ZA infusion in alloHSCT patients with either osteoporosis (T -score < ,2.5) or rapid bone loss post-alloHSCT. An uncontrolled, prospective study of 12 consecutive patients receiving ZA, predominantly within the first year post-HSCT. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the spine and proximal femur pretransplant, pre-ZA and post-ZA. The median annualized percentage change in total hip BMD between the pretransplant scan and the scan immediately before ZA was ,13% (range, ,51 to +3.6%). After ZA treatment, the total hip BMD increased by a median of +3.3% (range, ,20.4 to +14.8%) in 75% of patients. The median annualized percentage change in femoral neck BMD between the pretransplant scan and the scan immediately before ZA was ,13.2% (range, ,40 to +1.0%). Post-ZA, femoral neck BMD increased by a median of +1.4% (range, ,22.2 to +33.6%). Only one patient continued to lose bone from the femoral neck post-ZA infusion. The median annualized percentage change in spinal BMD pretransplant was ,12.5% (range, ,38 to +6.9%). Post-ZA, spinal BMD decreased by a median of ,2.8% (range, ,27.6 to +24.4%). Four patients continued to lose bone from the spine post-ZA. ZA reduces bone loss in most patients after alloHSCT. Our data require confirmation in a larger prospective, randomized study. [source] From basic research to the bedside: efficacy of topical treatment with pseudocatalase PC-KUS in 71 children with vitiligoINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2008Karin U. Schallreuter MD Background The epidermal accumulation of hydrogen peroxide (H2O2) has been documented in vitiligo. Aim To assess the effect on disease cessation and repigmentation of the reduction/removal of H2O2 using low-dose, narrow-band, ultraviolet-B (UV-B)-activated pseudocatalase PC-KUS in 71 children with vitiligo. Methods This uncontrolled and retrospective study included 45 girls and 26 boys (mean age, 10.3 years) who applied topical PC-KUS twice daily to the entire body surface without narrow-band UV-B dose increments. The affected body areas were documented by special photography at the first visit and after 8,12 months. The response was evaluated by two independent physicians as > 75% vs. < 75% total repigmentation of the face/neck, trunk, extremities, and hands/feet. Generalized (n = 61) and segmental (n = 10) vitiligo were evaluated as different entities. The effect of total-body, low-dose, narrow-band UV-B (0.15 mJ/cm2) monotherapy once daily without any increments and without application of PC-KUS was tested over 6 months in 10 children with vitiligo vulgaris (mean age, 8.4 years). Results One hundred per cent cessation was observed in 70 of the 71 children. More than 75% repigmentation was achieved in 66 of 71 patients on the face/neck, 48 of 61 on the trunk, and 40 of 55 on the extremities; however, repigmentation on the hands/feet was disappointing (five of 53). The response was independent of skin color, age of onset, duration of disease, other demographic features, and previous treatments. The follow-up after narrow-band UV-B monotherapy showed no significant repigmentation in all areas. Seven of 10 patients showed progression of their vitiligo. Conclusion A reduction in epidermal H2O2 using low-dose, narrow-band UV-B-activated pseudocatalase PC-KUS is an effective treatment for childhood vitiligo which can be safely performed at home. [source] Observer-based stabilization of linear switching systemsINTERNATIONAL JOURNAL OF ROBUST AND NONLINEAR CONTROL, Issue 14 2009Paolo Caravani Abstract The discrete component of the hybrid state of a discrete-time linear switching system is assumed to be uncontrolled and unobserved. Conditions of stabilizability for this class of systems are given in terms of a new definition of control invariance, based on the realization of a discrete observer that permits reconstruction of the discrete-state in certain intervals of the time basis. This paper highlights the relationship between the minimum dwell time of the system and its stabilizability. An almost complete characterization of stabilizability is offered in terms of certain subsets of the continuous-state space. These sets are amenable to tractable parametric procedures for controller synthesis. Copyright © 2008 John Wiley & Sons, Ltd. [source] The Role of Small Towns in Regional Development and Poverty Reduction in GhanaINTERNATIONAL JOURNAL OF URBAN AND REGIONAL RESEARCH, Issue 2 2008GEORGE OWUSU Abstract Ghana, like many other countries in sub-Saharan Africa, lacks a clearly articulated urban development strategy. Urban growth has been rapid but largely uncontrolled. Ghana's adoption of a decentralization programme in 1988 focused some attention on small towns. The country's more recent adoption of the Millennium Development Goals and other specific poverty reduction strategies requires more concerted state promotion of small towns. Improved service provision and delivery through small towns is a necessary component of any successful poverty reduction or regional development strategy. Résumé Le Ghana, comme de nombreux autres pays de l'Afrique subsaharienne, manque de stratégie d'aménagement urbain claire et explicite. L'expansion urbaine a été rapide et généralement non maîtrisée. Le Ghana ayant lancé un programme de décentralisation en 1988, les petites villes ont bénéficié d'un certain intérêt. L'adoption plus récente des Objectifs du Millénaire pour le Développement, ainsi que d'autres stratégies de réduction de la pauvreté, implique davantage de concertation dans la promotion gouvernementale des petites villes. Une amélioration de la mise à disposition des services dans les petites villes constitue un élément nécessaire à toute réussite en matière de réduction de la pauvreté ou de stratégie de développement régional. [source] Californian mixed-conifer forests under unmanaged fire regimes in the Sierra San Pedro Mártir, Baja California, MexicoJOURNAL OF BIOGEOGRAPHY, Issue 1 2000R. A. Minnich Abstract Aim,This study appraises historical fire regimes for Californian mixed-conifer forests of the Sierra San Pedro Mártir (SSPM). The SSPM represents the last remaining mixed-conifer forest along the Pacific coast still subject to uncontrolled, periodic ground fire. Location,The SSPM is a north,south trending fault bound range, centred on 31°N latitude, 100 km SE of Ensenada, Baja California. Methods,We surveyed forests for composition, population structure, and historical dynamics both spatially and temporally over the past 65 years using repeat aerial photographs and ground sampling. Fire perimeter history was reconstructed based on time-series aerial photographs dating from 1942 to 1991 and interpretable back to 1925. A total of 256 1-ha sites randomly selected from aerial photographs were examined along a chronosequence for density and cover of canopy trees, density of snags and downed logs, and cover of non-conifer trees and shrubs. Twenty-four stands were sampled on-the-ground by a point-centred quarter method which yielded data on tree density, basal area, frequency, importance value, and shrub and herb cover. Results,Forests experience moderately intense understory fires that range in size to 6400 ha, as well as numerous smaller, low intensity burns with low cumulative spatial extent. SSPM forests average 25,45% cover and 65,145 trees per ha. Sapling densities were two to three times that of overstory trees. Size-age distributions of trees , 4 cm dbh indicate multi-age stands with steady-state dynamics. Stands are similar to Californian mixed conifer forests prior to the imposition of fire suppression policy. Livestock grazing does not appear to be suppressing conifer regeneration. Main conclusions,Our spatially-based reconstruction shows the open forest structure in SSPM to be a product of infrequent, intense surface fires with fire rotation periods of 52 years, rather than frequent, low intensity fires at intervals of 4,20 years proposed from California fire-scar dendrochronology (FSD) studies. Ground fires in SSPM were intense enough to kill pole-size trees and a significant number of overstory trees. We attribute long fire intervals to the gradual build-up of subcontinuous shrub cover, conifer recruitment and litter accumulation. Differences from photo interpretation and FSD estimates are due to assumptions made with respect to site-based (point) sampling of fire, and nonfractal fire intensities along fire size frequency distributions. Fire return intervals determined by FSD give undue importance to local burns which collectively use up little fuel, cover little area, and have little demographic impact on forests. [source] Melatonin and sleep disorders associated with intellectual disability: a clinical reviewJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 1 2007S. G. Sajith Abstract Background Melatonin is used to treat sleep disorders in both children and adults with intellectual disability (ID), although it has no product license for such use. The evidence for its efficacy, potential adverse effects and drug interactions are reviewed in the context of prescribing to people with ID. Methods A literature search was performed using multiple electronic databases. More literature was obtained from the reference lists of papers gathered through the searches. Results Most of the studies were uncontrolled and the few controlled trials available were of small size. Melatonin appears effective in reducing sleep onset latency and is probably effective in improving total sleep time in children and adolescents with ID. It appears to be ineffective in improving night-time awakenings. Melatonin is relatively safe for short-term use. Its safety for long-term use is not established. Potential drug interactions, possible effects on puberty and concerns regarding the use of melatonin in epilepsy, asthma and depressive disorders are discussed. Conclusions Melatonin appears to be an effective sleep-initiator for children and adolescents with ID and probably has a similar effect for adults. There may be heterogeneity of response depending on the nature of the sleep problem and cause of the ID or associated disabilities. Further studies are necessary before firm conclusions can be drawn and guidelines for the use of melatonin for people with ID formulated. [source] Community-based programmes to prevent falls in children: A systematic reviewJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 9-10 2005Rod McClure Objective: We systematically reviewed the literature to examine the evidence for the effectiveness of community-based interventions to reduce fall-related injury in children aged 0,16 years. Methods: We performed a comprehensive search of the literature using the following study selection criteria: community-based intervention study; target population was children aged 0,16 years; outcome measure was fall-related injury rates; and either a community control or historical control was used in the study design. Quality assessment and data abstraction were guided by a standardized procedure and performed independently by two authors. Results: Only six studies fitting the inclusion criteria were identified in our search and only two of these used a trial design with a contemporary community control. Neither of the high quality evaluation studies showed an effect from the intervention and while authors of the remaining studies reported effective falls prevention programmes, the pre- and post-intervention design, uncontrolled for background secular trends, makes causal inferences from these studies difficult. Conclusion: There is a paucity of research studies from which evidence regarding the effectiveness of community-based intervention programmes for the prevention of fall-related injury in children could be based. [source] Outer-sphere electron transfer metal-catalyzed polymerization of styrene using a macrobicyclic ligandJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 1 2008Craig A. Bell Abstract The CuBr-catalyzed polymerizations of styrene in the presence of a macrobicyclic mixed donor (N and S) encapsulating ligand, NH2capten, were carried out in toluene at 60 and 100 °C. The macrobicyclic nature of the ligand ensures that a transition metal ion is effectively encapsulated (caged) within the three-dimensional cavity, resulting in activation of radicals through an outer-sphere electron transfer mechanism. The kinetic data showed that the polymerizations were uncontrolled with little "living" behavior. The external orders of reaction in [CuBr], [NH2capten], and [CuBr2] were 0.5, 0.5, and close to zero, respectively, in agreement with the postulated mechanism of little or no deactivation of polymeric radicals and a significant amount of bimolecular termination. Although "living" behavior was not found using the cage ligand, it was decided that it would provide an ideal method for radical coupling experiments to make high-molecular weight multiblock copolymers from a difunctional PSTY (Br-PSTY-Br, PDI = 1.11). The coupling reaction of Br-PSTY-Br using CuBr/NH2capten and excess Cu(0) in toluene at 100 °C gave no loss of the starting Br-PSTY-Br. Changing the solvent to the aprotic DMSO resulted in a significant increase in the rate of consumption of starting Br-PSTY-Br, with over 87% being used in under 10 min at 60 °C. In addition, higher molecular weight species were also formed, suggesting that OSET gives little or no side reactions on this time scale. It was initially thought that to get such high rates of reaction that the SET-LRP disproportionation mechanism (2Cu(I) , Cu(0) + Cu(II)) was at play. However, UV,Vis experiments of the CuBr/NH2capten showed little or no disproportionation products. This important result suggests that DMSO catalyzes the OSET reaction through the stabilization of the radical-anion intermediate, which then rapidly fragments to a polymeric radical. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 146,154, 2008 [source] Iron halide mediated atom transfer radical polymerization of methyl methacrylate with N -alkyl-2-pyridylmethanimine as the ligandJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 19 2004Huiqi Zhang Abstract The controlled atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA) catalyzed by iron halide/N -(n -hexyl)-2-pyridylmethanimine (NHPMI) is described. The ethyl 2-bromoisobutyrate (EBIB)-initiated ATRP with [MMA]0/[EBIB]0/[iron halide]0/[NHPMI]0 = 150/1/1/2 was better controlled in 2-butanone than in p -xylene at 90 °C. Initially added iron(III) halide improved the controllability of the reactions in terms of molecular weight control. The p -toluenesulfonyl chloride (TsC1)-initiated ATRP were uncontrolled with [MMA]0/[TsC1]0/[iron halide]0/[NHPMI]0 = 150/1/1/2 in 2-butanone at 90 °C. In contrast to the EBIB-initiated system, the initially added iron(III) halide greatly decreased the controllability of the TsC1-initiated ATRP. The ration of iron halide to NHPMI significantly influenced the controllability of both EBIB and TsC1-initiated ATRP systems. The ATRP with [MMA]0/[initiator]0/[iron halide]0/[NHPMI]0 = 150/1//1/2 provided polymers with PDIs , 1.57, whereas those with [iron halide]0/[NHPMI]0 = 1 resulted in polymers with PDIs as low as 1.35. Moreover, polymers with PDIs of approximately 1.25 were obtained after their precipitation from acidified methanol. The high functionality of the halide end group in the obtained polymer was confirmed by both 1H NMR and a chain-extenstion reaction. Cyclic voltammetry was utilized to explain the differing catalytic behaviors of the in situ -formed complexes by iron halide and NHPMI with different molar ratios. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4882,4894, 2004 [source] Synthesis of proton-conducting membranes by the utilization of preirradiation grafting and atom transfer radical polymerization techniquesJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 4 2002Svante Holmberg Abstract The atom transfer radical polymerization (ATRP) of styrene onto poly(vinylidene fluoride)- graft -poly(vinylbenzyl chloride) (PVDF- g -PVBC) membranes was investigated. Novel membranes were designed for fuel-cell applications. The benzyl chloride groups in the PVDF- g -PVBC membranes functioned as initiators, and a Cu-based catalytic system with the general formula Cu(n)Xn/ligand [where X is Cl or Br and the ligand is 2,2,-bipyridyl (bpy)] was employed for the ATRP. In addition, 10 vol % dimethylformamide was added for increased solubility of the catalyst complex in styrene. The system was homogeneous, except for the membrane, when the initiator/copper halide/ligand/monomer molar ratio was 1/1/3/500. As anticipated, the fastest polymerization rate of styrene was observed with the copper bromide/bpy-based catalyst system. The reaction rate was strongly temperature-dependent within the studied temperature interval of 100,130 °C. The degree of grafting increased linearly with time, thereby indicating first-order kinetics, regardless of the polymerization temperature. Furthermore, 120 °C was the maximum polymerization temperature that could be used in practice because the membrane structure was destroyed at higher temperatures. The degree of styrene grafting reached 400% after 3 h at 120 °C. Such a high degree of grafting could not be reached with conventional uncontrolled radiation-induced grafting methods because of termination reactions. On the basis of an Arrhenius plot, the activation energy for the homogeneous ATRP of styrene was 217 kJ/mol. The prepared membranes became proton-conducting after sulfonation of the polystyrene grafts. The highest conductivity measured for the prepared membranes was 70 mS/cm, which is comparable to the values normally measured for commercial Nafion membranes. The scanning electron microscopy/energy-dispersive X-ray results showed that the membranes had to be grafted through the matrix with both PVBC and polystyrene to become proton-conducting after sulfonation. In addition, PVDF- g -[PVBC- g -(styrene- block - tert -butyl acrylate)] membranes were also synthesized by ATRP. © 2002 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 40: 591,600, 2002; DOI 10.1002/pola.10146 [source] The effects of clonidine on symptoms and anorectal sensorimotor function in women with faecal incontinenceALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010A. E. Bharucha Aliment Pharmacol Ther 2010; 32: 681,688 Summary Background, Women with faecal incontinence and rectal urgency have increased rectal stiffness and sensation. Aim, To evaluate the effects of clonidine, an ,2 -adrenergic agonist, in faecal incontinence. Methods, In this open-label uncontrolled study, bowel symptoms and anorectal functions (anal pressures, rectal compliance, and sensation) were assessed before and during treatment with transdermal clonidine (0.2 mg daily, 4 weeks) in 12 women with urge-predominant faecal incontinence. Results, Clonidine reduced the frequency (17.8 ± 3.1 before vs. 8.8 ± 3.9 after, P = 0.03) and number of days with faecal incontinence (11.8 ± 1.6 before vs. 6.1 ± 1.8 after, P = 0.02), faecal incontinence symptom severity score (max = 13, 8.3 ± 0.7 vs. 5.6 ± 0.9, P < 0.01), and allowed patients to defer defecation for a longer duration (P = 0.03). Although overall effects on anorectal functions were not significant, the treatment-associated reduction in faecal incontinence episodes was associated with increased rectal compliance (r = ,0.58, P < 0.05) and reduced rectal sensation. (r = ,0.73, P = 0.007 vs. desire to defecate pressure threshold). Conclusions, Clonidine improves symptoms in women with faecal incontinence; this improvement is associated with increased rectal compliance and reduced rectal sensitivity. A controlled study is necessary to confirm these observations. [source] Depressive symptoms and suicidal ideation during isotretinoin treatment: a 12-week follow-up study of male Finnish military conscriptsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 11 2009LMH Rehn Abstract Objective, To investigate the putative association between isotretinoin treatment and depressive symptoms or suicidal ideation among Finnish male military conscripts. Methods, Consecutive acne patients were enrolled into an uncontrolled, prospective 12-week follow-up study conducted at the Central Military Hospital, Helsinki, Finland. Of the 135 patients prescribed isotretinoin, 126 (93.3%) completed the follow-up. Depression and suicidal ideation were investigated with the Beck Depression Inventory (BDI) at baseline, weeks 4,6, and weeks 10,12. Results, BDI mean score was low at baseline and declined further significantly (p < 0.001) during the follow-up from 3.0 (SD 3.948) to 1.8 (SD 3.783) among patients on isotretinoin. Moreover, the proportion of patients with clinically significant depressive symptoms (BDI , 10) declined non-significantly from 7.1 % to 3.2 %. Suicidal ideation was reported by 17 (13.5 %) patients at baseline and 9 (7.1%) patients at the end of the follow-up (NS). During the follow-up, one non-depressed patient attempted suicide while intoxicated by alcohol. Conclusion, On group level, isotretinoin seems not to be typically associated with treatment-emergent depression or suicidal ideation among young men. However, the possibility that individual patients may be susceptible for mood effects of isotretinoin as a rare idiosyncratic reaction can not be excluded. [source] An open study of antibiotics for the treatment of pre-pouch ileitis following restorative proctocolectomy with ileal pouch,anal anastomosisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009S. D. MCLAUGHLIN Summary Background, Pre-pouch ileitis is a recently described condition which may occur following restorative proctocolectomy. Its aetiology remains unknown and only one study has reported the effect of treatment. We report a series of fourteen patients treated and followed up with repeat pouchoscopy. Aim, To study the effectiveness of antibiotics for the treatment of pre-pouch ileitis following restorative proctocolectomy with ileal pouch,anal anastomosis. Methods, Fourteen consecutive patients with symptomatic pre-pouch ileitis were treated with ciprofloxacin 500 mg b.d. and metronidazole 400 mg b.d. for 28 days. All had concurrent pouchitis. Symptomatic, endoscopic and histological assessment was performed before and following treatment using the pouchitis disease activity index (PDAI). Symptomatic remission was defined as a score of 0 in the clinical component of the PDAI. Results, Twelve (86%) patients experienced symptomatic remission. Stool frequency fell from a median of 12 (range 8,20) to 6 (4,17) (P = 0.002). There was a significant reduction in the anatomical length of pre-pouch ileitis with nine (64%) patients having either a resolution or a reduction in length of pre-pouch ileitis from a median of 10 cm (range 3,20 cm) to a median of 1 cm (range 0,10 cm) (P = 0.007). Conclusion, Combination antibiotic therapy in this uncontrolled study appears effective in reducing the length of pre-pouch ileitis and in inducing symptomatic remission in most patients whether or not its extent is reduced. [source] Intrafamilial transmission of hepatitis C virus: a systematic reviewJOURNAL OF VIRAL HEPATITIS, Issue 2 2000Ackerman To examine the risk of hepatitis C virus (HCV) transmission between patients infected with HCV and their household members (siblings, offspring and parents), as well as their stable heterosexual partners, a systematic search of the MEDLINE database was undertaken for all relevant articles published up to June 1997. English language publications or those supplemented with an English abstract that reported studies concerning hepatitis C, and household, intrafamilial, sexual and intraspousal transmission of HCV, were reviewed. Data from uncontrolled and controlled studies were collected and analysed separately. Studies reporting the exclusive use of first-generation anti-HCV antibodies without supplemental tests were excluded. Pre- or postnatal mother-to-child transmission of HCV and homosexual and heterosexual transmission of HCV among non-permanent couples were not included. Unweighted data from individual studies were pooled for each category of family member. Data were also analysed separately for Japanese and non-Japanese studies because there is evidence that intrafamilial transmission may differ, based on endemicity of the viral infection. Comparisons were drawn only from controlled studies that reported the prevalence of HCV in family members of both HCV-positive and HCV-negative controls. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated for each family category. In uncontrolled studies, the pooled prevalence of anti-HCV among 4250 stable sexual contacts of patients with HCV-related chronic liver disease (CLD) was 13.48%, while the pooled prevalence of anti-HCV among 580 stable sexual contacts of patients who contracted HCV as a result of multiple transfusions was 2.41%. In controlled studies, the pooled prevalence of anti-HCV among 175 siblings and household contacts of patients with CLD was 4.0% compared with 0% among 109 contacts of anti-HCV-negative controls (OR 9.75, 95% CI 0.91 ad infinitum). The pooled prevalence of anti-HCV among offspring of Japanese HCV-infected CLD patients was 17% compared with 10.4% among offspring of HCV-negative Japanese controls (OR 1.77, 95% CI 1.21,2.58, P=0.002). The pooled prevalence of anti-HCV among spouses of non-Japanese HCV-infected CLD patients was 15.2% compared with 0.9% in the spouses of non-Japanese HCV-negative controls (OR 20.57, 95% CI 6.05,84.08, P=0.0001). The prevalence of anti-HCV among non-Japanese offspring and Japanese spouses of HCV-infected patients was not increased compared with controls. HCV genotype homology and mutant analysis studies in pairs of HCV-infected patients and their HCV-infected contacts showed that concordant genotype homology was found in 66% of non-sexual contacts and in 74% of sexual contacts. Sequence homology of greater than 92% was found in 19 out of 35 pairs. Hence, evidence exists that familial, non-sexual and sexual transmission of HCV does occur. In Japanese patients, transmission probably occurs in younger family members while, in non-Japanese patients, transmission probably occurs at an older age, after contact with an HCV-infected spouse. [source] The relationship between dosing of alosetron and discontinuation patterns reported by patients participating in a follow-up programmeALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2007P. TENNIS Summary Background Alosetron was reintroduced for treatment of irritable bowel syndrome with a risk management programme in November 2002. Recommended starting dosage was 1 mg/day for 4 weeks. If symptoms remained uncontrolled, dosage could be changed to 2 mg/day. Aim To describe alosetron dosages and associated patient characteristics from the Lotronex follow-up survey programme. Methods Patients reported dosages of alosetron at start and regular follow-up intervals. Analyses were limited to patients with the potential to have at least 1 year of follow-up (enrolled between 9 December 2002 and 31 December 2003). Results At baseline, 75% of 2817 respondents reported starting on 1 mg/day, 17% on 2 mg/day and 8% on other doses. Adherence to recommended starting dosage did not vary by status at end of follow-up, previous alosetron experience or age. At last reported dose, 50% of respondents were using 1 mg/day; 29% were using 2 mg/day. Discontinuation was not related to baseline doses. Longer times to discontinuation were associated with previous use, symptoms for more than 6 months and dose change throughout follow-up. Conclusions High adherence to recommended dosing at baseline and follow-up suggests that the risk management programme is encouraging safe use of alosetron, including adherence to dosing recommendations. [source] | ||||||||||||||||||||||||||||||||||||||||||||||