An evaluation of animal models for behavioural recovery after brain damage

Hersenletsel, te wijten aan neurodegeneratieve ziekten, zoals dementie van het Alzheimer Type (DAT), herseninfarkten of trauma, leidt, afhankelijk van het volume en delocatie van de beschadiging, tot stoornissen in cognitieve processen zoals aandacht, leren en geheugen. De kwaliteit van het leven van patiënten met hersenletsel en hun onmiddellijke omgeving heeft hier onder te lijden. Helaas zijn er nog geen therapeutica beschikbaar die het herstel van cognitieve funkties verbeteren en/of versnellen. ... Zie: Samenvatting

microRNA-371a-3p as informative biomarker for the follow-up of testicular germ cell cancer patients

Purpose: α-fetoprotein (AFP) and human chorionic gonadotropin subunit beta (B-HCG) are informative serum biomarkers for the primary diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. About 20% of TGCC patients with a non-seminoma (NS) and about 80% with a seminoma (SE) are, however, negative for these biomarkers. Embryonic stem cell microRNAs (miRs) may serve as promising alternative serum biomarkers. Here we investigated a retrospective series of serum samples from selected TGCC patients who developed a relapse in time to test the possible additional value of the serum-based ampTSmiR test compared to the conventional serum-based protein biomarkers for follow-up. Methods: We investigated 261 retrospective serum samples of six selected fully evaluated TGCC patients with a proven relapse using the ampTSmiR test for miR-371a-3p, miR-373-3p, and miR-367-3p and compared the results to those of the conventional protein biomarkers. Results: At primary diagnosis, elevated serum B-HCG, AFP and LDH levels were found to be informative in 4/6, 3/6 and 3/6 patients, respectively. At primary diagnosis the levels of miR-371a-3p and miR-373-3p were elevated in 4/4, and miR-367-3p in 3/4 patients. For two cases no starting serum sample was available for retrospective miR analysis. Residual disease (overlooked by histopathological examination) was detected in one case by miR-371a-3p only. The miR-371a-3p level was increased in one patient two months before detection of an intracranial metastasis. B-HCG was informative in 3/4 and the ampTSmiR test in 4/4 patients with a relapse or residual disease. None of the biomarkers were informative for the detection of residual mature teratoma. Conclusions: The ampTSmiR test is more sensitive than the conventional TGCC protein biomarkers for the detection o

Dopamine-neurotransmission and nociception in zebrafish: An anti-nociceptive role of dopamine receptor drd2a

Dopamine (DA) is an important modulator in nociception and analgesia. Spinal DA receptors are involved in descending modulation of the nociceptive transmission. Genetic variations within DA neurotransmission have been associated with altered pain sensitivity and development of chronic pain syndromes. The variant rs6277 in dopamine receptor 2 a (drd2a) has been associated with a decreased D2 receptor availability and increased nociception. The aim of this study is to further characterize the role of DA neurotransmission in nociception and the anti-nociceptive function of drd2a. The phenotype caused by rs6277 was modelled in zebrafish larvae using morpholino's and the effect on nociception was tested using a validated behavioural assay. The anti-nociceptive role of drd2a was tested using pharmacological intervention of D2 agonist Quinpirole. The experiments demonstrate that a decrease in drd2a expression results in a pro-nociceptive behavioural phenotype (P = 0.016) after a heat stimulus. Furthermore, agonism of drd2a with agonist Quinpirole (0.2 mu M) results in dose-dependent anti-nociception (P = 0.035) after a heat stimulus. From these results it is concluded that the dopamine receptor drd2a is involved in anti-nociceptive behaviour in zebrafish. The model allows further screening and testing of genetic variation and treatment involved in nociception

Patellofemoral alignment and geometry and early signs of osteoarthritis are associated in patellofemoral pain population

Background: Patellofemoral pain (PFP) patients show increased prevalence of patellar malalignment. Structural and alignment abnormalities of the patellofemoral joint (PFJ) may play a role in development of PFP and patellofemoral osteoarthritis (PFOA). Objectives: Evaluating associations of patellofemoral alignment and femoral geometry with bony and cartilaginous abnormalities in PFP patients and healthy control subjects. Methods: Data from a case-control study were used (64 PFP subjects, 70 control subjects, 57% female, age 23.2 (6.4)). Alignment and femoral geometry measu

Is patellofemoral pain a precursor to osteoarthritis?

Objectives It has been hypothesized that patellofemoral pain, a common knee condition in adolescents and young adults, may be a precursor of degenerative joint changes and may ultimately lead to patellofemoral osteoarthritis. Since both conditions share several mechanical disease characteristics, such as altered contact area between the femur and patella and increased joint stress, we investigated whether these conditions share similar and different shape characteristics of the patella compared with normal controls. Methods This cross-sectional study compared three different study populations: 32 patellofemoral pain subjects (mean age, 32 years (22 to 45); 72% female); 56 isolated radiological patellofemoral osteoarthritis subjects (mean age, 54 years (44 to 58); 89% female); and 80 healthy control subjects (mean age, 52 years (44 to 58); 74% female). Measurements included questionnaires, and lateral and skyline radiographs of the knee. Two separate 30-point 2D statistical shape models of the patella were created from the lateral and skyline radiographs. A general linear model was used to test for differences in standardized shape modes (a specific shape variant of the patella) between patellofemoral osteoarthritis, patellofemoral pain, and controls, using Bonferroni correction and adjustment for body mass index and gender. Results Five shape modes showed statistically significant differences between groups: skyline modes 1 (p < 0.001), 8 (p = 0.004), and 10 (p < 0.001); and lateral modes 5 (p = 0.002) and 7 (p = 0.002). Skyline mode 8 and lateral mode 5 were similar for patellofemoral osteoarthritis and patellofemoral pain populations, while being statistically significant different from the control group. Conclusion Our results indicate that patellofemoral pain and patellofemoral osteoarthritis share similar shape characteristics, which are different from control subjects. These findings support the proposed continuum disease model of patellofemoral pain predisposing to the development of patellofemoral osteoarthritis

Are Patellofemoral Joint Alignment and Shape Associated With Structural Magnetic Resonance Imaging Abnormalities and Symptoms Among People With Patellofemoral Pain?

BACKGROUND:: Patellofemoral malalignment has been observed among people with patellofemoral pain (PFP) and may be associated with the presence of imaging features of osteoarthritis, symptoms, and function.PURPOSE:: To determine whether patellofemoral joint alignment and bony shape are associated with (1) cartilage, bone, and soft tissue morphological abnormalities defined on magnetic resonance imaging (MRI) and (2) reported symptoms and function among people with PFP.STUDY DESIGN:: Cross-sectional study; Level of evidence, 3.METHODS:: Participants (mean ± SD age, 30.2 ± 9.5 years; range, 14-50 years; 78 females, 58.6%) completed questionnaires regarding demographics, pain, symptoms, and function and underwent a 3-T MRI scan of their more symptomatic eligible knee. Structural MRI abnormalities were scored with the MOAKS (Magnetic Resonance Imaging Osteoarthritis Knee Score), and MRI alignment and shape were measured with standardized methods. Associations among MOAKS features, PFP symptoms, and alignment and shape measures were evaluated with regression analyses (α = .05).RESULTS:: Minor cartilage defects were present in 22 (16.5%) participants, patellar osteophytes in 83 (62.4%), anterior femur osteophytes in 29 (21.8%), Hoffa synovitis in 81 (60.9%), and prefemoral fat pad synovitis in 49 (36.8%). A larger Insall-Salvati ratio was significantly associated with the presence of patellar osteophytes (odds ratio [OR], 51.82; 95% CI, 4.20-640.01), Hoffa synovitis (OR, 60.37; 95% CI, 4.66-782.61), and prefemoral fat pad synovitis (OR, 43.31; 95% CI, 4.28-438.72) in the patellofemoral joint. A larger patellar tilt angle was significantly associated with the presence of minor cartilage defects (OR, 1.10; 95% CI, 1.00-1.20), the presence of patellar osteophytes (OR 1.12; 95%CI 1.02-1.22), and prefemoral fat pad synovitis (OR, 1.11; 95% CI, 1.03-1.20) in the patellofemoral joint. Finally, a larger bisect offset was significantly associated with the presence of minor cartilage defects (OR, 1.05; 95% CI, 1.00-1.11) and patellar osteophytes (OR, 1.07; 95% CI, 1.01-1.14) in the patellofemoral joint. The majority of patellofemoral alignment measures were not associated with symptoms or function.CONCLUSION:: For people with PFP, the presence of morphological abnormalities defined on MRI appears to be related to particular patellofemoral alignment measures, including higher Insall-Salvati ratio (indicating patella alta), larger patellar tilt angle (indicating greater lateral tilt), and larger bisect offset (indicating greater lateral displacement). Hardly any associations were found with symptoms or function.

International patellofemoral osteoarthritis consortium: Consensus statement on the diagnosis, burden, outcome measures, prognosis, risk factors and treatment

Objective: To present the current status of knowledge in the field of patellofemoral (PF) osteoarthritis (OA) and formulate a research agenda in order to guide future research on this topic. Design: A 1-day meeting was organized with the aim to bring together international experts in the field to discuss the current state of knowledge on PF OA. Experts from multiple disciplines were invited based on their scientific publications in the field of PF OA and interest in the subject. Topics discussed include the diagnosis, impact, prognosis, and treatment of PF OA. Methods: Following context-setting presentations, an interactive discussion was held in order to achieve consensus on the PF OA topics of interest: (1) diagnosis and definition; (2) burden; (3) outcome measures; (4) prognosis; (5) risk factors, and (6) treatment. Groups of meeting attendees reviewed the literature on these topics and narratively summarized the current state of knowledge, and each group formulated research agenda items relevant to the specific topics of interest. Each consortium member consequently ranked the importance of all items on a 0–10 Numerical Rating Scale (NRS) (10 = extremely important, to 0 = not at all important). Results: After ranking all formulated items on importance, 6 of the 28 research agenda items formulated received an average of 7.5 points on the NRS. The most highly ranked items covered the fields of treatment, diagnosis, and definition of PF OA. Conclusions: We recommend to develop clear clinical criteria for PF OA and to reach consensus on the definition of PF OA by both radiographs and MRI. Additionally, more understanding is necessary to be able to distinguish PF symptoms from those arising from the tibiofemoral joint. More insight is needed on effective treatment strategies for PF OA; specifically, tailoring nonpharmacological treatments to individuals with PF OA, and determining whether isolated PF OA requires different treatment strategies than combined PF and tibiofemoral OA

Neoadjuvant concurrent chemoradiation with weekly paclitaxel and carboplatin for patients with oesophageal cancer: a phase II study

This study was performed to assess the efficacy and safety of preoperative chemoradiation consisting of carboplatin and paclitaxel and concurrent radiotherapy for patients with resectable (T2-3N0-1M0) oesophageal cancer. Treatment consisted of paclitaxel 50 mg m−2 and carboplatin AUC=2 on days 1, 8, 15, 22 and 29 and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week), followed by oesophagectomy. All 54 entered patients completed the chemoradiation without delay or dose-reduction. Grade 3–4 toxicities were: neutropaenia 15%, thrombocytopaenia 2%, and oesophagitis 7.5%. After completion of the chemoradiotherapy 63% had a major endoscopical response. Fifty-two patients (96%) underwent a resection. The postoperative mortality rate was 7.7%. All patients had an R0-resection. The pathological complete response rate was 25%, and an additional 36.5% had less than 10% vital residual tumour cells. At a median follow-up of 23.2 months, the median survival time has not yet been reached. The probability of disease-free survival after 30 months was 60%. In conclusion, weekly neoadjuvant paclitaxel and carboplatin with concurrent radiotherapy is a very tolerable regimen and can be given on an outpatient basis. It achieves considerable down staging and a subsequent 100% radical resection rate in this series. A phase III trial with this regimen is now ongoing