Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels

Objective Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [11C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [123I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. Methods The [123I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Results Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Conclusions Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications

Intraarticular corticosteroid for treatment of osteorthritis of the knee

BACKGROUND: Osteoarthritis (OA) is a common joint disorder. In the knee, injections of corticosteroids into the joint (intra-articular (IA)) may relieve inflammation, and reduce pain and disability. OBJECTIVES: To evaluate the efficacy and safety of IA corticosteroids in treatment of OA of the knee. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2003), MEDLINE, EMBASE, PREMEDLINE (all to July 2003), and Current Contents (Sept 2000). Specialised journals, trial reference lists and review articles were handsearched. SELECTION CRITERIA: Randomised controlled trials of IA corticosteroids for patients with OA of the knee: single/double blind, placebo-based/comparative studies, reporting at least one core OMERACT III outcome measure. DATA COLLECTION AND ANALYSIS: Methodological quality of trials was assessed, and data were extracted in duplicate. Fixed effect and random effects models, giving weighted mean differences (WMD), were used for continuous variables. Dichotomous outcomes were analysed by relative risk (RR). MAIN RESULTS: Twenty-six trials (1721 participants) comparing IA corticosteroid against placebo, against IA hyaluronan/hylan (HA products), against joint lavage, and against other IA corticosteroids, were included.IA corticosteroid was more effective than IA placebo for pain reduction (WMD -17.79; 95% confidence interval (CI) -25.02 to -10.55) and patient global assessment (the RR was 1.44 (95% CI 1.13 to 1.82)) at one week post injection with an NNT of 3 to 4 for both, based on n=185 for pain on 100 mm visual analogue scale (VAS) and n=158 for patient global assessment. Data on function were sparse at one week post injection and neither statistically significant nor clinically important differences were detected.There was evidence of pain reduction between two weeks (the RR was 1.81 (95% CI 1.09 to 3.00)) to three weeks (the RR was 3.11 (95% CI 1.61 to 6.01), but a lack of evidence for efficacy in functional improvement.At four to 24 weeks post injection, there was lack of evidence of effect on pain and function (small studies showed benefits which did not reach statistical or clinical importance, i.e. less than 20% risk difference). For patient global, there were three studies which consistently showed lack of effect longer than one week post injection. However, all were fairly small sample sizes (less than 50 patients per group). This was supported by another study which did not find statistically significant differences, at any time point, on a continuous measure of patient global assessment (100 mm VAS).In comparisons of corticosteroids and HA products, no statistically significant differences were in general detected at one to four weeks post injection. Between five and 13 weeks post injection, HA products were more effective than corticosteroids for one or more of the following variables: WOMAC OA Index, Lequesne Index, pain, range of motion (flexion), and number of responders. One study showed a difference in function between 14 to 26 weeks, but no differences in efficacy were detected at 45 to 52 weeks. In general, the onset of effect was similar with IA corticosteroids, but was less durable than with HA products.Comparisons of IA corticosteroids showed triamcinolone hexacetonide was superior to betamethasone for number of patients reporting pain reduction up to four weeks post injection (the RR was 2.00 (95% CI 1.10 to 3.63). Comparisons between IA corticosteroid and joint lavage showed no differences in any of the efficacy or safety outcome measures. AUTHORS' CONCLUSIONS: The short-term benefit of IA corticosteroids in treatment of knee OA is well established, and few side effects have been reported. Longer term benefits have not been confirmed based on the RevMan analysis. The response to HA products appears more durable. In this review, some discrepancies were observed between the RevMan 4.1 analysis and the original publication. These are likely the result of using secondary rather than primary data and the statistical methods available in RevMan 4.1. Future trials should have standardised outcome measures and assessment times, run longer, investigate different patient subgroups, and clinical predictors of response (those associated with inflammation and structural damage)

Reduction of inequalities in health: assessing evidence-based tools

BACKGROUND: The reduction of health inequalities is a focus of many national and international health organisations. The need for pragmatic evidence-based approaches has led to the development of a number of evidence-based equity initiatives. This paper describes a new program that focuses upon evidence- based tools, which are useful for policy initiatives that reduce inequities. METHODS: This paper is based on a presentation that was given at the "Regional Consultation on Policy Tools: Equity in Population Health Reports," held in Toronto, Canada in June 2002. RESULTS: Five assessment tools were presented. 1. A database of systematic reviews on the effects of educational, legal, social, and health interventions to reduce unfair inequalities is being established through the Cochrane and Campbell Collaborations. 2 Decision aids and shared decision making can be facilitated in disadvantaged groups by 'health coaches' to help people become better decision makers, negotiators, and navigators of the health system; a pilot study in Chile has provided proof of this concept. 3. The CIET Cycle: Combining adapted cluster survey techniques with qualitative methods, CIET's population based applications support evidence-based decision making at local and national levels. The CIET map generates maps directly from survey or routine institutional data, to be used as evidence-based decisions aids. Complex data can be displayed attractively, providing an important tool for studying and comparing health indicators among and between different populations. 4. The Ottawa Equity Gauge is applying the Global Equity Gauge Alliance framework to an industrialised country setting. 5 The Needs-Based Health Assessment Toolkit, established to assemble information on which clinical and health policy decisions can be based, is being expanded to ensure a focus on distribution and average health indicators. CONCLUSION: Evidence-based planning tools have much to offer the goal of equitable health development

Acupuncture, chiropractic and osteopathy use in Australia: a national population survey

Background There have been no published national studies on the use in Australia of the manipulative therapies, acupuncture, chiropractic or osteopathy, or on matters including the purposes for which these therapies are used, treatment outcomes and the socio-demographic characteristics of users. Methods This study on the three manipulative therapies was a component of a broader investigation on the use of complementary and alternative therapies. For this we conducted a cross-sectional, population survey on a representative sample of 1,067 adults from the six states and two territories of Australia in 2005 by computer-assisted telephone interviews. The sample was recruited by random digit dialling. Results Over a 12-month period, approximately one in four adult Australians used either acupuncture (9.2%), chiropractic (16.1%) or osteopathy (4.6%) at least once. It is estimated that, adult Australians made 32.3 million visits to acupuncturists, chiropractors and osteopaths, incurring personal expenditure estimated to be A$1.58 billion in total. The most common conditions treated were back pain and related problems and over 90% of the users of each therapy considered their treatment to be very or somewhat helpful. Adverse events are reported. Nearly one fifth of users were referred to manipulative therapy practitioners by medical practitioners. Conclusion There is substantial use of manipulative therapies by adult Australians, especially for back-related problems. Treatments incur considerable personal expenditure. In general, patient experience is positive. Referral by medical practitioners is a major determinant of use of these manipulative therapies

Recruiting Injection Drug Users: A Three-Site Comparison of Results and Experiences with Respondent-Driven and Targeted Sampling Procedures

Several recent studies have utilized respondent-driven sampling (RDS) methods to survey hidden populations such as commercial sex-workers, men who have sex with men (MSM) and injection drug users (IDU). Few studies, however, have provided a direct comparison between RDS and other more traditional sampling methods such as venue-based, targeted or time/space sampling. The current study sampled injection drug users in three U.S. cities using RDS and targeted sampling (TS) methods and compared their effectiveness in terms of recruitment efficiency, logistics, and sample demographics. Both methods performed satisfactorily. The targeted method required more staff time per-recruited respondent and had a lower proportion of screened respondents who were eligible than RDS, while RDS respondents were offered higher incentives for participation

Written information about individual medicines for consumers.

Medicines are the most common intervention in most health services. As with all treatments, those taking medicines need sufficient information: to enable them to take and use the medicines effectively, to understand the potential harms and benefits, and to allow them to make an informed decision about taking them. Written medicines information, such as a leaflet or provided via the Internet, is an intervention that may meet these purposes

KDM2B recruitment of the polycomb group complex, PRC1.1, requires cooperation between PCGF1 and BCORL1

Accepted author manuscriptKDM2B recruits H2A-ubiquitinating activity of a non-canonical Polycomb Repression Complex 1 (PRC1.1) to CpG islands, facilitating gene repres sion. We investigated the molecular basis of recruit ment using in vitro assembly assays to identify minimal components, subcomplexes, and domains required for recruitment. A minimal four-component PRC1.1 complex can be assembled by combining two separately isolated subcomplexes: the DNA binding KDM2B/SKP1 heterodimer and the hetero dimer of BCORL1 and PCGF1, a core component of PRC1.1. The crystal structure of the KDM2B/ SKP1/BCORL1/PCGF1 complex illustrates the crucial role played by the PCGF1/BCORL1 hetero dimer. The BCORL1 PUFD domain positions resi dues preceding the RAWUL domain of PCGF1 to create an extended interface for interaction with KDM2B, which is unique to the PCGF1-containing PRC1.1 complex. The structure also suggests how KDM2B might simultaneously function in PRC1.1 and an SCF ubiquitin ligase complex and the possible molecular consequences of BCOR PUFD internal tandem duplications found in pediatric kidney and brain tumors.Ye

The epidemiology and survival of extrapulmonary small cell carcinoma in South East England, 1970–2004

<p>Abstract</p> <p>Background</p> <p>Extrapulmonary small cell carcinoma (EPSCC) is a rare cancer and few studies describe its epidemiology. Our objectives were to compare the incidence and survival of EPSCC in South East England with small cell carcinoma of the lung (SCLC), to determine the most common anatomical presenting sites for EPSCC and to compare survival in EPSCC by disease stage and site of diagnosis.</p> <p>Methods</p> <p>We used data from the Thames Cancer Registry database for South East England between 1970 and 2004 to determine the incidence, most common anatomical sites, and survival by site, and stage of EPSCC. 1618 patients registered with EPSCC were identified. We calculated the age-standardised incidence rate for EPSCC using the European standard population and compared this to that for SCLC. We calculated survival using the Kaplan-Meier method for EPSCC and SCLC, and reported 3-year survival for different EPSCC anatomical sites and disease stages.</p> <p>Results</p> <p>The incidence of EPSCC was much lower than for SCLC, similar in males and females, and stable throughout the study period, with incidence rates of 0.45 per 100,000 in males and 0.37 in females during 2000–2004. In general, patients with EPSCC had a better 3-year survival (19%) than SCLC (5%). The most common anatomical sites for EPSCC were oesophagus (18%), other gastrointestinal (15%), genitourinary (20%), head and neck (11%), and breast (10%). Breast EPSCC had the best 3-year survival (60%) and gastrointestinal EPSCC the worst (7%).</p> <p>Conclusion</p> <p>This study suggests that EPSCC has a stable incidence and confirms that it presents widely, but most commonly in the oesophagus and breast. Site and extent of disease influence survival, with breast EPSCC having the best prognosis. Further studies using standardised diagnosis, prospective case registers for uncommon diseases and European cancer registries are needed to understand this disease.</p

Dichomitus squalens partially tailors its molecular responses to the composition of solid wood

White-rot fungi, such as Dichomitus squalens, degrade all wood components and inhabit mixed-wood forests containing both soft- and hardwood species. In this study, we evaluated how D. squalens responded to the compositional differences in softwood [guaiacyl (G) lignin and higher mannan content] and hardwood [syringyl/guaiacyl (S/G) lignin and higher xylan content] using semi-natural solid cultures. Spruce (softwood) and birch (hardwood) sticks were degraded by D. squalens as measured by oxidation of the lignins using 2D-NMR. The fungal response as measured by transcriptomics, proteomics and enzyme activities showed a partial tailoring to wood composition. Mannanolytic transcripts and proteins were more abundant in spruce cultures, while a proportionally higher xylanolytic activity was detected in birch cultures. Both wood types induced manganese peroxidases to a much higher level than laccases, but higher transcript and protein levels of the manganese peroxidases were observed on the G-lignin rich spruce. Overall, the molecular responses demonstrated a stronger adaptation to the spruce rather than birch composition, possibly because D. squalens is mainly found degrading softwoods in nature, which supports the ability of the solid wood cultures to reflect the natural environment.Peer reviewe