[The general practitioner in charge of treatment of patients with bipolar disorder: an exploratory study]. / De huisarts als primaire behandelaar van patiënten met een bipolaire stoornis: een exploratief onderzoek.

BACKGROUND: The role of the general practitioner (gp) in the treatment of severe psychiatric disorders, including bipolar disorder (bd), is under discussion. AIM: To investigate how many patients with a recognised bd are being treated for their illness exclusively in the setting of primary care and to find out how many patients are registrated as having bd on their gp's file. METHOD: We made an exploratory study in a gp's database containing data for 14,254 Dutch adult patients in the Amsterdam over a period of 3.5 years (2010-2013). RESULTS: We found that the gp was in charge of the treatment of bd in less than one patient per practice. The percentage of patients officially recognised as having bd in the database we studied was 0.15%, a percentage that is much lower than the percentage of bd in the Dutch population as a whole. There are several possible explanations for this discrepancy. CONCLUSION: Given these low numbers, it is unlikely that the gps can have adequate experience of giving their bd patients the latest type of treatment. In view of the increasing role played by gps in the treatment of bd, it is important that there is strong collaboration with specialised mental health care, and that a low threshold prevails for consultation and referral.

[Forcing patients with bipolar disorder to make a financial contribution to secondary psychiatric care may make them forsake care completely]. / Vraaguitval bij poliklinische patiënten met een bipolaire stoornis als gevolg van de eigen bijdrage in de tweedelijns-ggz.

BACKGROUND: In 2012 patients were required to make a personal financial contribution for secondary mental health care over and above their standard insurance fee. According to current guidelines, the majority of patients with bipolar disorder must be treated as outpatients at psychiatric clinics. It was to be expected that some patients would decide to discontinue their outpatient treatment on account of the newly imposed personal financial contribution. AIM: To obtain insight into the size and characteristics of the group of patients with bipolar disorder who were thinking about giving up treatment or had already decided to give it up because of the imposition of the personal financial contribution; also to find out which factors influenced patients' decisions and to discover how patients perceived the role of the GP as the provider of subsequent psychiatric care. METHOD: We conducted an exploratory study by sending a survey to all outpatients receiving treatment at three clinics specialising in the treatment of bipolar disorder. RESULTS: 640 patients responded to the survey (55% response); 15% of these patients were thinking about giving up treatment or had already decided to stop their treatment. They were influenced primarily by financial considerations. Two-thirds of the respondents did not consider that the GP was as a suitable alternative to outpatient care at a clinic. Even patients with moderate to serious symptoms were considering leaving secondary care. CONCLUSION: The obligatory financial contribution for secondary mental health care could have considerable consequences for a small number of patients with severe mood disorder who are currently treated as outpatients in secondary facilities. The increase in the compulsory & squo;own risk' insurance fee as from 2013 could have similar consequences.

Risk factors of recurrent hamstring injuries: a systematic review.

BACKGROUND: Although recurrent hamstring injury is a frequent problem with a significant impact on athletes, data on factors determining the risk for a recurrent hamstring injury are scarce. OBJECTIVE: To systematically review the literature and provide an overview of risk factors for re-injury of acute hamstring muscle injuries. STUDY DESIGN: Prospective studies on risk factors for re-injury following acute hamstring injuries were systematically reviewed. Medical databases and reference lists of the included articles were searched. Two reviewers independently selected potential studies and assessed methodological quality; one reviewer extracted the data. A best-evidence synthesis of all studied risk factors was performed. RESULTS: Of the 131 articles identified, five prospective follow-up studies fulfilled our inclusion criteria. These studies reported a recurrence incidence of 13.9-63.3% in the same playing season up to 2 years after initial injury. Limited evidence for three risk factors and one protective factor for recurrent hamstring injury was found; patients with a recurrent hamstring injury had an initial injury with a larger volume size as measured on MRI (47.03 vs 12.42 cm(3)), more often had a Grade 1 initial trauma (Grade 0: 0-30.4%; Grade 1: 60.9-100%; Grade 2: 8.7%) and more often had a previous ipsilateral anterior cruciate ligament (ACL) reconstruction (66.6% vs 17.1%) independent of graft selection. Athletes in a rehabilitation programme with agility/stabilisation exercises rather than strength/stretching exercises had a lower risk for re-injury (7.7% vs 70%). No significant relationship with re-injury was found for 11 related determinants. There was conflicting evidence that a larger cross-sectional area is a risk factor for recurrent hamstring injury. CONCLUSIONS: There is limited evidence that athletes with a larger volume size of initial trauma, a Grade 1 hamstring injury and a previous ipsilateral ACL reconstruction are at increased risk for recurrent hamstring injury. Athletes seem to be at lower risk for re-injury when following agility/stabilisation exercises.

IL4-10 Fusion Protein Shows DMOAD Activity in a Rat Osteoarthritis Model.

OBJECTIVE: Ideally, disease-modifying osteoarthritis (OA) drugs (DMOAD) should combine chondroprotective, anti-inflammatory, and analgesic effects in a single molecule. A fusion protein of interleukin-4 (IL-4) and IL-10 (IL4-10 FP) possesses these combined effects. In this study, the DMOAD activity of rat IL4-10 FP (rIL4-10 FP) was tested in a rat model of surgically induced OA under metabolic dysregulation. DESIGN: rIL4-10 FP was produced with HEK293F cells. Bioactivity of purified rIL4-10 FP was determined in a whole blood assay. Male Wistar rats (n = 20) were fed a high-fat diet (HFD) to induce metabolic dysregulation. After 12 weeks, OA was induced according to the Groove model. Two weeks after OA induction, rats were randomly divided into 2 groups and treated with 10 weekly, intra-articular injections of either rIL4-10 FP (n = 10) or phosphate buffered saline (PBS; n = 10). Possible antibody formation was evaluated using ELISA, cartilage degeneration and synovial inflammation were evaluated by histology and mechanical allodynia was evaluated using the von Frey test. RESULTS: Intra-articular injections with rIL4-10 FP significantly reduced cartilage degeneration (P = 0.042) and decreased mechanical allodynia (P < 0.001) compared with PBS. Only mild synovial inflammation was found (nonsignificant), limiting detection of putative anti-inflammatory effects. Multiple injections of rIL4-10 FP did not induce antibodies against rIL4-10 FP. CONCLUSION: rIL4-10 FP showed chondroprotective and analgesic activity in a rat OA model with moderate cartilage damage, mild synovial inflammation, and pain. Future studies will need to address whether less frequent intra-articular injections, for example, with formulations with increased residence time, would also lead to DMOAD activity.

Local and systemic inflammatory lipid profiling in a rat model of osteoarthritis with metabolic dysregulation.

OBJECTIVE: Bioactive oxidised lipids (oxylipins) are important signalling mediators, capable of modulating the inflammatory state of the joint and anticipated to be of importance in joint homeostasis and status of osteoarthritis. The aim of this study was to quantify oxylipin levels in plasma and synovial fluid from rats with experimentally induced osteoarthritis to investigate the potential role of oxylipins as a marker in the disease process of early osteoarthritis. DESIGN: Forty rats were randomly allocated to a standard or high-fat diet group. After 12 weeks, local cartilage damage was induced in one knee joint in 14 rats of each diet group. The remaining 6 rats per group served as controls. At week 24, samples were collected. Oxylipin levels were quantified by liquid chromatography-mass spectrometry. RESULTS: Overall, 31 lipid-derived inflammatory mediators were detected in fasted plasma and synovial fluid. Principal component analysis identified four distinct clusters associated with histopathological changes. Diet induced differences were evident for 13 individual plasma oxylipins, as well as 5,6-EET in synovial fluid. Surgical-model induced differences were evident for three oxylipins in synovial fluid (15-HETE, 8,9-DHET and 17R-ResolvinD1) with a different response in lipid concentrations for synovial fluid and plasma. CONCLUSIONS: We demonstrate the quantification of oxidised lipids in rat plasma and synovial fluid in a model of early experimental osteoarthritis. Oxylipins in the synovial fluid that were altered as consequence of the surgically induced osteoarthritis were not represented in the plasma. Our findings suggest differential roles of the oxylipins in the local versus peripheral compartment.

Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis.

Major hallmarks of osteoarthritis (OA) are cartilage degeneration, inflammation and osteophyte formation. COX-2 inhibitors counteract inflammation-related pain, but their prolonged oral use entails the risk for side effects. Local and prolonged administration in biocompatible and degradable drug delivery biomaterials could offer an efficient and safe treatment for the long-term management of OA symptoms. Therefore, we evaluated the disease-modifying effects and the optimal dose of polyesteramide microspheres delivering the COX-2 inhibitor celecoxib in a rat OA model. Four weeks after OA induction by anterior cruciate ligament transection and partial medial meniscectomy, 8-week-old female rats (n = 6/group) were injected intra-articular with celecoxib-loaded microspheres at three dosages (0.03, 0.23 or 0.39 mg). Unloaded microspheres served as control. During the 16-week follow-up, static weight bearing and plasma celecoxib concentrations were monitored. Post-mortem, micro-computed tomography and knee joint histology determined progression of synovitis, osteophyte formation, subchondral bone changes, and cartilage integrity. Systemic celecoxib levels were below the detection limit 6 days upon delivery. Systemic and local adverse effects were absent. Local delivery of celecoxib reduced the formation of osteophytes, subchondral sclerosis, bone cysts and calcified loose bodies, and reduced synovial inflammation, while cartilage histology was unaffected. Even though the effects on pain could not be evualated directly in the current model, our results suggest the application of celecoxib-loaded microspheres holds promise as novel, safe and effective treatment for inflammation and pain in OA.

[Intakes for (day) clinical psychotherapy. A cohort study]. / Intakes voor (deeltijd) klinische psychotherapie. Een cohortonderzoek.

Little is known about the type of patient who is referred for clinical psychotherapy. A descriptive, retrospective cohort study was performed involving 100 patients who attended a (day) clinic for personality, anxiety and eating disorders. Sociodemographic and clinical characteristics of these patients are described. Most of the patients had multiple disorders of a serious nature, displayed a high degree of functional impairment and were relatively treatment-resistant. Of the 70% who were diagnosed as requiring treatment, 79% agreed to have the treatment that was offered.

Direct observation of sub-picosecond equilibration of excitation energy in the light-harvesting antenna of Rhodospirillum rubrum.

Excitation energy transfer in the light-harvesting antenna of Rhodospirillum rubrum was studied at room temperature using sub-picosecond transient absorption measurements. Upon excitation of Rs. rubrum membranes with a 200 fs, 600 nm laser flash in the Qx transition of the bacteriochlorophyll-a (BChl-a) absorption, the induced transient absorption changes in the Qy region were monitored. In Rs. rubrum membranes the observed delta OD spectrum exhibits ground state bleaching, excited state absorption and stimulated emission. Fast Qx --> Qy relaxation occurs in approximately 100-200 fs as reflected by the building up of stimulated emission. An important observation is that the zero-crossing of the transient difference absorption (delta OD) spectrum exhibits a dynamic redshift from 863 to 875 nm that can be described with by a single exponential with 325 fs time constant. The shape of the transient difference spectrum observed in a purified subunit of the core light-harvesting antenna, B820, consisting of only a single interacting pair of BChl-as, is similar to the spectrum observed in Rs. rubrum membranes and clearly different from the spectrum of BChl-a in a protein/detergent mixture. In the B820 and monomeric BChl-a preparations the 100-200 fs Qx --> Qy relaxation is still observed, but the dynamic redshift of the delta OD spectrum is absent. The spectral kinetics observed in the Rs. rubrum membranes are interpreted in terms of the dynamics of excitation equilibration among the antenna subunits that constitute the inhomogeneously broadened antenna. A simulation of this process using a set of reasonable physical parameters is consistent with an average hopping time in the core light harvesting of 220-270 fs, resulting in an average single-site excitation lifetime of 50-70 fs. The observed rate of this equilibration process is in reasonable agreement with earlier estimations for the hopping time from more indirect measurements. The implications of the findings for the process of excitation trapping by reaction centers will be discussed.

Trapping kinetics in mutants of the photosynthetic purple bacterium Rhodobacter sphaeroides: influence of the charge separation rate and consequences for the rate-limiting step in the light-harvesting process.

The primary light-harvesting processes, energy transfer in the light-harvesting antenna, and trapping of the excited states by reaction centers were studied in several mutant strains of the photosynthetic purple bacterium Rhodobacter sphaeroides. The mutants had reaction centers in which the rates of electron transfer were modified by site-directed mutations at the M210 position. Low-intensity pump-probe laser spectroscopy was used to monitor the absorbance transients in the Qy region of the antenna pigments, and it was found that despite a wide variation in charge separation rates within the RC, produced by the alterations at Tyr M210, there was relatively little corresponding variation in the overall trapping rate. These effects of the mutations on the trapping kinetics demonstrate that the rate-limiting step of the overall light-harvesting process is the transfer of the excitations from the antenna to the reaction center.

Molecular cytogenetic analysis of term placentae suspected of mosaicism using fluorescence in situ hybridization.

In first-trimester chorionic villus sampling (CVS) for prenatal diagnosis, abnormal chromosomal findings, such as mosaicism, trisomies, or suspect abnormal karyotypes, are found more frequently than at amniocentesis. The fact that these chromosomal abnormalities do not always reflect the fetal karyotype but may be restricted to the placenta is a major problem in diagnosis and counselling. In this paper we present the results of fluorescence in situ hybridization (FISH) studies on interphase nuclei of three term placentae investigated because of false-positive findings at first-trimester CVS. The chorionic villi of the first case showed a mosaic chromosome pattern involving a trisomy 10 cell line and a normal cell line, those of the second case a total trisomy 8 cell line, while in the third case a complete monosomy X was found. Follow-up amniocentesis in each of these three cases revealed a normal karyotype. By using FISH, we were able to confirm the presence of the aberrant cell lines, which were all confined to one part of the placenta. FISH on interphase nuclei allows the investigation of large numbers of cells for the existence of numerical chromosome aberrations in a quick and reliable way.