Pain trajectories and neuropathic pain symptoms following lung cancer surgery: A prospective cohort study.

BACKGROUND: Persistent postsurgical pain (PPSP) after lung cancer surgery is common and current definitions are based on evaluations at a single time point after surgery. Pain intensity and symptoms may however fluctuate and change over time, and be impacted by multiple and shifting factors. Studies of postoperative recovery patterns and transition from acute to chronic pain are needed for further investigation of preventive measures and treatments to modify unfavourable recovery paths. METHODS: In this explorative study, 85 patients undergoing surgery due to either presumptive or confirmed lung cancer reported pain intensities bi-monthly for 12 months. Pain trajectories during recovery were investigated, using group-based trajectory modelling. Associations with possible risk factors for PPSP, including clinical variables and anxiety and depression score (HADS), were also explored. RESULTS: A trajectory model containing three 12-month pain recovery groups was computed. One group without PPSP fully recovered (50%) within two to three months. Another group with mild-intensity PPSP followed a protracted recovery trajectory (37%), while incomplete recovery was observed in the last group (13%). Acute postoperative pain and younger age were associated with a less favourable recovery trajectory. More neuropathic pain symptoms were observed in patients with incomplete recovery. CONCLUSIONS: Three clinically relevant recovery trajectories were identified, based on comprehensive pain tracking. Higher acute postoperative pain intensity was associated with an unfavourable pain recovery trajectory. SIGNIFICANCE STATEMENT: Understanding the transition from acute to chronic postoperative pain and identifying preoperative risk factors is essential for the development of targeted treatments and the implementation of preventive measures. This study (1) identified distinct recovery trajectories based on frequent pain assessment follow-ups for 12 months after surgery and (2) evaluated risk factors for unfavourable postoperative pain recovery paths. Findings suggest that early higher postoperative pain intensity is associated with an unfavourable long-term recovery path.

Quantitative sensory testing, psychological profiles and clinical pain in patients with psoriatic arthritis and hand osteoarthritis experiencing pain of at least moderate intensity.

BACKGROUND: Chronic pain is the hallmark symptom of joint diseases. This study examined the differences in quantitative sensory testing between patients with psoriatic arthritis (PsA), hand osteoarthritis (hand-OA) and a pain-free control group and differences between patients with and without concomitant fibromyalgia (cFM). METHODS: All patients and pain-free controls were assessed using pressure pain thresholds (PPT), temporal summation of pain (TSP), conditioned pain modulation (CPM) and clinical pain intensities. Psychological distress was assessed with the Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, and Pittsburgh Sleep Quality Index. Disability was assessed with the Health Assessment Questionnaire and pain quality with the painDETECT questionnaire. cFM was identified using the revised 2016 American College of Rheumatology diagnostic criteria. RESULTS: Patients with hand-OA (n = 75) or PsA (n = 58) had statistically significant lower PPTs and CPM, greater TSP, and higher scores of psychological distress (p < 0.05) than controls (n = 20). Patients with cFM (58%) had higher scores of depression (p = 0.001), anxiety (p = 0.004), catastrophizing (p = 0.012), disability (p < 0.001), higher painDETECT score (p = 0.001), TSP (p = 0.027), and reduced sleep quality (p = 0.021) when compared to patients without cFM. CONCLUSION: Patients with hand-OA and PsA exhibited signs of pain sensitization and a higher degree of psychological distress and disability than pain-free individuals. Patients with cFM had greater TSP, painDETECT score, disability, catastrophizing, and reduced sleep quality, than patients without, indicating greater degree of pain sensitization, psychological burden, and disability. STATEMENT OF SIGNIFICANCE: This paper shows that a significant proportion of patients with hand osteoarthritis and psoriatic arthritis with moderate pain intensity have significantly increased signs of pain sensitization and markers of psychological distress. A large proportion of these patients fulfil the criteria for concomitant fibromyalgia and these patients show even greater propensity towards pain sensitization and psychological distress.

Investigation of pain sensitivity following 3 nights of disrupted sleep in healthy individuals.

BACKGROUND: Poor quality sleep is a common complaint among people with chronic pain. The co-occurrence of poor sleep quality and chronic pain often comes with increased pain intensity, more disability and a higher cost of healthcare. Poor sleep has been suggested to affect measures of peripheral and central pain mechanisms. To date, sleep provocations are the only models proven to affect measures of central pain mechanisms in healthy subjects. However, there are limited studies investigating the effect of several nights of sleep disruption on measures of central pain mechanisms. METHODS: The current study implemented three nights of sleep disruption with three planned awakenings per night in 30 healthy subjects sleeping at home. Pain testing was conducted at the same time of day at baseline and follow-up for each subject. Pressure pain thresholds were assessed bilaterally on the infraspinatus and gastrocnemius muscles. Using handheld pressure algometry, suprathreshold pressure pain sensitivity and area were also investigated on the dominant infraspinatus muscle. Cuff-pressure pain detection and tolerance thresholds, temporal summation of pain and conditioned pain modulation were investigated using cuff-pressure algometry. RESULTS: Temporal summation of pain was significantly facilitated (p = 0.022), suprathreshold pain areas (p = 0.005) and intensities (p < 0.05) were significantly increased, and all pressure pain thresholds were decreased (p < 0.005) after sleep disruption compared to baseline. CONCLUSIONS: The current study found that three consecutive nights of sleep disruption at home induced pressure hyperalgesia and increased measures of pain facilitation in healthy subjects, which is consistent with previous findings. SIGNIFICANCE: Poor quality of sleep is often experienced by patients with chronic pain, with the most common complaint being nightly awakenings. This exploratory study is the first to investigate changes in measures of central and peripheral pain sensitivity in healthy subjects after sleep disruptions for three consecutive nights without any restrictions on total sleep time. The findings suggest that disruptions to sleep continuity in healthy individuals can induce increased sensitivity to measures of central and peripheral pain sensitization.

Associations of Stages of Objective Memory Impairment with Cerebrospinal Fluid and Neuroimaging Biomarkers of Alzheimer's Disease.

OBJECTIVE: To investigate cerebrospinal fluid (CSF) and neuroimaging correlates of Stages of Objective Memory Impairment (SOMI) based on Free and Cued Selective Reminding Test (FCSRT) performance, and to evaluate the effect of APOE ε4 status on this relationship. METHODS: Data from 586 cognitively unimpaired individuals who had FCSRT, CSF, and volumetric magnetic resonance imaging (MRI) measures available was used. We compared CSF measures of ß-amyloid (Aß42/Aß40 ratio), phosphorylated tau (p-Tau181), total tau (t-Tau), hippocampal volume, and PIB-PET mean cortical binding potential with partial volume correction (MCBP) among SOMI groups in the whole sample and in subsamples stratified by APOE ε4 status. RESULTS: Participants had a mean age of 67.4 (SD=9.1) years, had 16.1 (SD=2.6) years of education, 57.0% were female, and 33.8% were APOE ε4 positive. In the entire sample, there was no significant difference between SOMI stages in Aß42/Aß40 ratio, p-Tau181, t-Tau, or PIB-PET MCBP when adjusted for age, sex, and education. However, higher SOMI stages had smaller hippocampal volume (F=3.29, p=0.020). In the stratified sample based on APOE ε4 status, in APOE ε4 positive individuals, higher SOMI stages had higher p-Tau181 (F=2.94, p=0.034) higher t-Tau (F=3.41, p=0.019), and smaller hippocampal volume (F=5.78, p<0.001). There were no significant differences in CSF or imaging biomarkers between SOMI groups in the APOE ε4 negative subsample. CONCLUSION: Cognitively normal older individuals with higher SOMI stages have higher in-vivo tau and neurodegenerative pathology only in APOE ε4 carriers. These original results indicate the potential usefulness of the SOMI staging system in assessing of tau and neurodegenerative pathology.

Potential diagnostic value of a type X collagen neo-epitope biomarker for knee osteoarthritis.

OBJECTIVE: Phenotypic changes of chondrocytes toward hypertrophy might be fundamental in the pathogenesis of osteoarthritis (OA), of which type X collagen (Col10) is a well-known marker. The purpose was to develop a specific immunoassay for blood quantification of a newly identified neo-epitope of type Col10 to assess its diagnostic value for radiographic knee OA. METHODS: A neo-epitope of Col10 was identified in urine samples from OA patients. A monoclonal antibody against the neo-epitope was produced in Balb/C mice. The enzyme responsible for the cleavage was identified. Immunohistochemical detection of this neo-epitope was performed on human OA cartilage. An immunoassay (Col10neo) was developed and quantified in two clinical studies: the C4Pain-003 and the NYU OA progression study. Receiver operating characteristic curve (ROC) curve analysis was carried out to evaluate the discriminative power of Col10neo between OA and rheumatoid arthritis (RA). RESULTS: A neo-epitope specific mAb was produced. The Cathepsin K-generated neo-epitope was localized to the pericellular matrix of chondrocytes, while its presence was extended and more prominent in superficial fibrillation in the cartilage with advanced degradation. In the C4Pain study, a higher level of Col10neo was seen in subjects with greater KL grade. The group of the highest tertile of Col10neo included more subjects with KL3-4. In the NYU study, Col10neo was statistically higher in OA than control or RA. ROC curve analysis revealed area under the curve was 0.88 (95% CI 0.81-0.94). CONCLUSION: Our findings indicate that Col10neo linked to hypertrophic chondrocytes could be used as a diagnostic biochemical marker for knee OA.

Effects of repeated conditioning pain modulation in healthy volunteers.

BACKGROUND: Conditioned pain modulation (CPM) may be impaired in chronic pain patients compared with healthy subjects. The CPM-effect is the difference between pain sensitivity assessments (test-stimuli) with and without a painful conditioning stimulus. CPM has been extensively explored but effects of repeated CPM-effects and differences between repeated CPM assessments and comparable control conditions are less studied. METHODS: In 20 healthy men, four 5-min bouts with a test-stimulus in the beginning and midway were applied by cuff-algometry to the dominant leg. The 2nd test-stimulus in each bout was conditioned in parallel by a painful cuff pressure on the contralateral leg. A control-session was performed without conditioning. The conditioning intensity was 70% of the pressure-pain tolerance threshold (PTT) assessed at baseline. Pain detection threshold (PDT) was extracted from test-stimuli. CPM/Control-effects were calculated as second minus first test-stimulus, and netCPM-effects were calculated as the difference between CPM-effects and Control-effects. RESULTS: Pain detection threshold increased in all four bouts (p < 0.02) compared to the unconditioned test-stimulus and compared to the 2nd test-stimulus in bout1, bout3 and bout4 of the control-session (p < 0.04). In the control-session, the 1st test-stimulus PDT increased from bout1 to bout2, bout3 and bout4 (p < 0.03). The netCPM-effect increased progressively over the four bouts (p = 0.03). CONCLUSION: Conditioned pain modulation-effects were maintained over four consecutive bouts and in the control-session repeated pain thresholds assessments habituated more than in the CPM-session leading to an increase in netCPM-effect over the four bouts. SIGNIFICANCE: Conditioning pain modulation can be assessed in 5-min intervals by cuff algometry with a fixed conditioning stimulus. Without applying conditioning stimuli the pain sensitivity of test-stimuli habituated. As a consequence, it can be speculated that the conditioning stimulus may negate the temporal habituation effects during repeated sessions, whereas this may not be the case for unconditioned stimuli. Applying both conditioned and unconditioned repeated test-stimuli may be a way to assess different parts of the pain modulatory system, and a model for measuring a netCPM-effect, which could indicate a balance between habituation and sensitization, is proposed.

Electrical stimulation for evoking offset analgesia: A human volunteer methodological study.

BACKGROUND: Offset analgesia (OA) is a disproportionally large decrease in the pain perception in response to a small decrease in the stimulation intensity. Traditionally, heat stimulation has been used to evoke OA. The aim of this study was to investigate whether OA could be evoked by electrical stimulation. METHODS: Healthy volunteers (N = 24) underwent two OA-experimental sessions consisting of heat stimuli intensities of 48-49-48 °C (traditional OA-paradigm) and electrical stimuli at 150%-180%-150% of the electrical pain perception (EPP) threshold. The three stimuli were delivered for 5 s (STIM1), 5 s (STIM2) and 20 s (STIM3), respectively. The sessions were randomized to the dominant or nondominant volar forearm. Two control sessions were performed with 30 s constantly heat (48 °C) and electrical stimuli (150% of the EPP) (CONTROL-STIM). In all sessions, the pain intensities were constantly rated on a Visual Analog Scale (VAS, 0-10). RESULTS: Significantly reduced STIM3 VAS ratings as compared to the CONTROL-STIM were reported for heat (1.81 ± 0.54; p < 0.001) and electrical (2.12 ± 0.42; p < 0.001) stimuli. The degrees of OA produced by heat and electrical stimuli were similar. A significantly positive correlation was found between thermal and electrical OA-effects (r = 0.48, p < 0.02). CONCLUSIONS: These findings demonstrate that electrical stimulation can elicit significant OA in humans indicating that the peripheral receptors can be bypassed and still evoke OA. Application of the electrical OA model may be of interest for further basic and clinical investigations as a potential new biomarker for central pain inhibition and provide the option to back-translate the technology to animals to understand the underlying neurobiology. SIGNIFICANCE: Electrical stimulation can elicit offset analgesia in humans, indicating that this perceptual modification can be obtained even bypassing peripheral receptors.

Aggrecanase degradation of type III collagen is associated with clinical knee pain.

There is a lack of biochemical markers for non-invasive and objective assessment of symptomatic osteoarthritis (OA). Aggrecanase activity has been shown to be associated with joint deterioration and symptomatic disease through the degradation of extracellular matrix proteins, such as type III collagen. Our study aimed to identify and develop a novel biomarker by measuring an aggrecanase-mediated type III collagen neoepitope, and correlate levels of this biomarker with OA joint pain. Mass spectrometric analysis of purified type III collagen, degraded by the aggrecanase A Disintigrin and Metalloproteinase with Thrombospondin motif (ADAMTS), revealed a fragment generated by ADAMTS-1, -4 and -8. A monoclonal antibody was raised against the neoepitope of this fragment (COL3-ADAMTS) and a competitive ELISA was developed and tested; using serum samples from a cross-sectional cohort of patients with different degrees of knee OA (n = 261). The COL3/ADAMTS ELISA was technically robust and specific for the ADAMTS-1, -4 and -8 generated neoepitope. COL3/ADAMTS was released form cytokine stimulated synovial cultures, indicating a biologic link between the marker and synovium. In OA patients, serum COL3/ADAMTS was independently associated with pain scores (rho = -0.13-0.17, p < 0.05). This association was associated significantly with the presence of radiographic OA. Together, these data indicate that COL3/ADAMTS could be a marker of early osteoarthritis and the underlining pathology.

Offset analgesia: The role of peripheral and central mechanisms.

BACKGROUND: Offset Analgesia (OA) can be evoked by a three-heat-stimulus train (T1-T2-T3), with T1 (5 s) and T3 (20 s) having the same temperature (e.g. 48 °C) and T2 (5 s) being slightly higher (1-3 °C). OA is defined as a disproportional pain reduction caused by the slight temperature decrease from T2 to T3. As the pain modulatory mechanisms behind OA are still poorly understood, the current study aimed to investigate the role of peripheral and central mechanisms by applying heat stimuli to the same location and to different unilateral and bilateral locations. METHOD: Young healthy volunteers participated in the study. A 'standard-OA' paradigm (48-49-48 °C) was applied to the non-dominant volar forearm (T1-T2-T3 applied on the same location). 'Unilateral-OA' trials were applied on three different locations of the non-dominant volar forearm (the same dermatome). 'Bilateral-OA' trials were applied by shifting T1-T2-T3 between dominant and non-dominant volar forearms. A constant stimulus of 48 °C was applied as control for the evoked pain. The pain intensities were continuously recorded using an electronic visual analogue scale. RESULTS: The largest pain intensity reduction was reported for the 'standard-OA' paradigm (p < 0.001) compared with the control stimulus. Both 'Unilateral-OA' and 'Bilateral-OA' trials caused a significant pain reduction (p < 0.05) compared with the control; however, the pain reduction was less than that evoked by 'standard-OA' (p < 0.05). CONCLUSION: This study showed that OA could be elicited when the stimuli were applied both to the same and to different locations (ipsi- and contralateral) indicating that peripheral as well as central mechanisms are involved in mediating OA. SIGNIFICANCE: This study investigated offset analgesia by applying thermal painful stimuli to the ipsi- and bilateral forearms in healthy subjects and found that both peripheral and central mechanisms seem to mediate offset analgesia.

The association between histological, macroscopic and magnetic resonance imaging assessed synovitis in end-stage knee osteoarthritis: a cross-sectional study.

OBJECTIVES: To investigate the association between magnetic resonance imaging (MRI), macroscopic and histological assessments of synovitis in end-stage knee osteoarthritis (KOA). METHODS: Synovitis of end-stage osteoarthritic knees was assessed using non-contrast-enhanced (CE), contrast-enhanced magnetic resonance imaging (CE-MRI) and dynamic contrast-enhanced (DCE)-MRI prior to (TKR) and correlated with microscopic and macroscopic assessments of synovitis obtained intraoperatively. Multiple bivariate correlations were used with a pre-specified threshold of 0.70 for significance. Also, multiple regression analyses with different subsets of MRI-variables as explanatory variables and the histology score as outcome variable were performed with the intention to find MRI-variables that best explain the variance in histological synovitis (i.e., highest R2). A stepped approach was taken starting with basic characteristics and non-CE MRI-variables (model 1), after which CE-MRI-variables were added (model 2) with the final model also including DCE-MRI-variables (model 3). RESULTS: 39 patients (56.4% women, mean age 68 years, Kellgren-Lawrence (KL) grade 4) had complete MRI and histological data. Only the DCE-MRI variable MExNvoxel (surrogate of the volume and degree of synovitis) and the macroscopic score showed correlations above the pre-specified threshold for acceptance with histological inflammation. The maximum R2-value obtained in Model 1 was R2 = 0.39. In Model 2, where the CE-MRI-variables were added, the highest R2 = 0.52. In Model 3, a four-variable model consisting of the gender, one CE-MRI and two DCE-MRI-variables yielded a R2 = 0.71. CONCLUSION: DCE-MRI is correlated with histological synovitis in end-stage KOA and the combination of CE and DCE-MRI may be a useful, non-invasive tool in characterising synovitis in KOA.

User-independent assessment of conditioning pain modulation by cuff pressure algometry.

BACKGROUND: The use of conditioning pain modulation (CPM) is hampered by poor reproducibility and lack of user-independent paradigms. This study refined the CPM paradigm by applying user-independent cuff algometry. METHODS: In 20 subjects, the CPM effect of conditioning with cuff stimulation on the arm was investigated by pain test stimuli on the contralateral leg before and in parallel with different cuff conditionings (10, 30, 60 kPa/60 s; 30, 60 kPa/10 s). As test stimulus, another cuff was inflated (1 kPa/s) until the subjects detected the pain tolerance threshold (PTT) during which the pain detection threshold (PDT) and the pressure at a pain intensity of 6 cm on a 10-cm visual analogue scale (PVAS6) were extracted. For comparison, pressure pain thresholds (PPTs) as test stimuli were recorded by the user-dependent handheld pressure algometry. Combinations of cuff locations for conditioning (pain intensity standardized) and contralateral test stimuli were additionally evaluated (leg-arm, leg-leg, arm-thigh). The test-retest reliability in two sessions 1 month apart was assessed in five CPM protocols. RESULTS: In all protocols, the PDT, PVAS6 and PTT increased during conditioning compared with baseline (p < 0.05). The CPM effect (i.e. conditioning minus baseline) for PVAS6, PTT and PPT increased for increasing conditioning intensities (p < 0.05). The CPM effects were not significantly different for changes in conditioning durations or conditioning/test stimulus locations. In two sessions, the CPM effects for PVAS6 and PTT assessed after 60 s of conditioning on the leg/thigh showed the highest intra-class correlations (0.47-0.73), where they were 0.04-0.6 for PPTs. CONCLUSIONS: The user-independent cuff algometry is reliable for CPM assessment and for supra-pain threshold test stimuli better than the user-dependent technology. SIGNIFICANCE: A user-independent CPM technique where the conditioning is controlled by one cuff stimulation, and the test-stimulus is provided by another cuff stimulation. This study shows that cuff algometry is reliable for CPM assessment.

Comparing test-retest reliability and magnitude of conditioned pain modulation using different combinations of test and conditioning stimuli.

This study aimed to compare the reliability and magnitude of conditioned pain modulation (CPM) by applying different test stimuli (TS) and conditioning stimuli (CS). Twenty-six healthy male participants were recruited in the study of two identical sessions. In each session, four TS (electrical, heat, handheld, and cuff pressure algometry) were applied before and during CS (cold pressor test (CPT) or cuff algometry). The same procedure was repeated with 45-min intervals, but with the other CS. Five thresholds were measured including four pain detection thresholds from four TS and pain tolerance threshold from cuff TS (cuff PTT). Intraclass correlation coefficient (ICC (3,1)) and coefficient of variation (CV) were calculated as measures of reliability. The reliability of TS before and during CS was good for all combinations (ICC: 0.60-0.96, CV: 2.2-22.9%), but the reliability of the CPM effect varied (ICC: 0.04-0.53, CV: 63.6-503.9%). The most reliable combinations were considered to be the handheld pressure pain threshold with CPT (ICC: 0.49, CV: 63.6%) and the cuff pressure pain threshold with CPT (ICC: 0.44, CV: 107.6%). Significant CPM effects were found for all combinations, except the combinations of electrical and heat pain thresholds with cuff CS, which indicates the novel classification of the CPM mechanism. The combinations of handheld pressure and heat pain threshold with CPT would provide the minimum sample size to detect the significant CPM changes in further studies. It is beneficial to provide and compare both ICC and CV to design further clinical trials.

Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers.

This study investigated whether itch induced by intra-epidermal histamine is subjected to modulation by a standardized conditioned pain modulation (CPM) paradigm in 24 healthy volunteers. CPM was induced by computer-controlled cuff pressure algometry and histamine was introduced to the volar forearm by skin prick test punctures. Moreover, neurogenic inflammation and wheal reactions induced by histamine and autonomic nervous system responses (heart rate variability and skin conductance) were monitored. CPM did not modulate the intensity of histamine-induced itch suggesting that pruriceptive signaling is not inhibited by pain-recruited endogenous modulation, however, CPM was found to aggravate histamine-induced neurogenic inflammation, likely facilitated by efferent sympathetic fibers.

A mechanism-based pain sensitivity index to characterize knee osteoarthritis patients with different disease stages and pain levels.

BACKGROUND: In a cohort of well-characterized patients with different degrees of knee osteoarthritis (OA) and pain, the aims were to utilize mechanism-based quantitative sensory testing (QST) to (1) characterize subgroups of patients; (2) analyse the associations between clinical characteristics and QST; and (3) develop and apply a QST-based knee OA composite pain sensitivity index for patient classification. METHODS: Two hundred seventeen OA pain patients and 64 controls were included. Kellgren and Lawrence (KL) grading scores were obtained, and pressure pain thresholds (PPTs), temporal summation of pain to repeated painful pressure stimulation and conditioning pain modulation (CPM) were assessed. Associations between pain score/area/duration, radiological findings and QST-related parameters were analysed. A pain sensitivity index was developed and applied based on PPT, temporal summation and CPM. z-Score, as statistical tool, was calculated for statistically comparing the pain index of a single patient with a healthy control group. RESULTS: High knee pain associated with low KL grade showed particular signs of pain sensitization. Patients showed significant associations between clinical knee pain intensity/duration and lowering of knee PPTs (p < 0.01), facilitation of temporal summation (p < 0.01), reduction of CPM function (p < 0.01) and high pain sensitivity index (p < 0.01). The index classified 27-38% of the OA patients and 3% of the controls as highly sensitive with no association to KL. The index increased for high knee pain intensities and long pain duration. CONCLUSIONS: Radiological scores, contrary to clinical pain intensity/duration, were poorly associated with QST parameters. The pain sensitivity index could classify OA patients with different degrees of OA and pain.

Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover.

OBJECTIVES: Osteoarthritis (OA) is a degenerative disease with a subset of patients experiencing joint inflammation, but C-reactive protein (CRP) has shown limited use in OA as a diagnostic marker. The aim was to identify subpopulations of patients with high or low levels of acute (high sensitive CRP (hsCRP)) and/or matrix metalloproteinase (MMP) derived inflammation (CRPM) and investigate the subpopulations' association with biomarkers of collagen degradation and Kellgren-Lawrence (KL) score. METHODS: hsCRP, CRPM and MMP-degraded type I, II and III collagen (type I collagen degraded by MMP (C1M), type II collagen degraded by MMP (C2M) and type III collagen degraded by MMP (C3M)) were quantified by enzyme linked immunosorbent assays (ELISA) in serum of 342 patients with symptomatic knee OA of which 60 underwent total knee replacement (TKR). KL was obtained. Patients were divided into quartiles by hsCRP and CRPM levels, where Q1 and Q4 were low or high in both. The biomarker levels of healthy adults provided in the ELISA kits were used as reference level. RESULTS: hsCRP was elevated in TKR (5.9(3.6-8.2 95% confidence interval (CI)) µg/mL) compared to reference level (3 µg/mL), while CRPM was highly elevated with OA independent of KL (10-14 ng/mL) compared to reference level (5 ng/mL). Q4 had higher KL than Q1 (P < 0.001), Q2 (P = 0.017) and Q3 (P < 0.001). C1M, C2M and C3M were lowest in Q1. C1M was elevated in Q3 compared to Q2 (P < 0.001), whereas C3M was lower (P = 0.019). CONCLUSION: A bigger proportion of patients were elevated in CRPM compared to hsCRP, indicating MMP-derived inflammation as a component of OA. Moreover, the levels of MMP-degraded collagens differed between the subgroups segregated by inflammation, indicating distinctively different subpopulation selected by inflammation.

Jugular venous pooling during lowering of the head affects blood pressure of the anesthetized giraffe.

How blood flow and pressure to the giraffe's brain are regulated when drinking remains debated. We measured simultaneous blood flow, pressure, and cross-sectional area in the carotid artery and jugular vein of five anesthetized and spontaneously breathing giraffes. The giraffes were suspended in the upright position so that we could lower the head. In the upright position, mean arterial pressure (MAP) was 193 +/- 11 mmHg (mean +/- SE), carotid flow was 0.7 +/- 0.2 l/min, and carotid cross-sectional area was 0.85 +/- 0.04 cm(2). Central venous pressure (CVP) was 4 +/- 2 mmHg, jugular flow was 0.7 +/- 0.2 l/min, and jugular cross-sectional area was 0.14 +/- 0.04 cm(2) (n = 4). Carotid arterial and jugular venous pressures at head level were 118 +/- 9 and -7 +/- 4 mmHg, respectively. When the head was lowered, MAP decreased to 131 +/- 13 mmHg, while carotid cross-sectional area and flow remained unchanged. Cardiac output was reduced by 30%, CVP decreased to -1 +/- 2 mmHg (P < 0.01), and jugular flow ceased as the jugular cross-sectional area increased to 3.2 +/- 0.6 cm(2) (P < 0.01), corresponding to accumulation of approximately 1.2 l of blood in the veins. When the head was raised, the jugular veins collapsed and blood was returned to the central circulation, and CVP and cardiac output were restored. The results demonstrate that in the upright-positioned, anesthetized giraffe cerebral blood flow is governed by arterial pressure without support of a siphon mechanism and that when the head is lowered, blood accumulates in the vein, affecting MAP.

Identification of QTLs influencing combustion quality in Miscanthus sinensis Anderss. II. Chlorine and potassium content.

Chlorine and potassium content are important traits related to combustion quality of Miscanthus species. These traits were analysed in a cross between F(1.1) and F(1.7) entries of Miscanthus sinensis Anderss, both lines offspring of the cross between MS-90-2 and MS-88-110. Quantitative trait locus (QTL) analyses were performed on a previous linkage map constructed with the offspring cross mapping strategy. The mapqtl 4.0 package was used to perform QTL analyses. Six potential QTLs were detected with data collected over a 2-year period. Of these, four were associated with chlorine and two with potassium. These results could be used as an initial step to develop a marker-aided selection programme for biomass with low mineral content.

Identification of QTLs influencing agronomic traits in Miscanthus sinensis Anderss. I. Total height, flag-leaf height and stem diameter.

We have developed the first quantitative trait locus (QTL) analyses for agronomic traits in a cross between F(1.1) (P1) and F(1.7) (P7) entries of Miscanthus sinensis Anderss. Both lines are offspring of the cross between MS-90-2 and MS-88-110. A map based on random amplified polymorphic DNA markers previously constructed was used to perform the QTL analyses. This map was developed using a new mapping strategy that has been designated offspring cross. Eleven QTLs were detected for height, panicle height and diameter using the programme mapqtl 4.0 and the multiple QTL method. QTL significance was determined using several analyses, including Kruskal-Wallis analyses, empirical determination of LOD critical values using permutation tests, QTLs validation with field data over 2 years and co-localization of QTLs for correlated traits. The results obtained could be the first step in developing a marker-assisted selection programming in this species for biomass production.

Iodixanol in paediatric gastrointestinal imaging: safety and efficacy comparison with iohexol.

Iodixanol (Visipaque) is a dimeric, non-ionic iodinated contrast medium that is isotonic with blood at all clinically relevant concentrations. Iodixanol was compared in a randomized, double blind, parallel group, phase III multicentre trial with a monomeric, non-ionic contrast medium, iohexol (Omnipaque), at two concentrations assessing safety, tolerability and radiographic efficacy during contrast enhanced gastrointestinal radiography examinations of children. 154 children entered the trial; 152 formed the safety population and 147 the efficacy population. All examinations were performed following standard departmental practice. Children were assigned into either a high or low concentration group (iodixanol, 150 mgI ml(-1) and 320 mgI ml(-1) vs iohexol, 140 mgI ml(-1) and 300 mgI ml(-1)). The primary outcome measure for efficacy was the overall quality of visualization, which was assessed using a 100 mm visual analogue scale (VAS). The secondary efficacy variables assessed were quality of contrast opacification, mucosal coating and overall quality of diagnostic information. Safety evaluation involved patient follow-up for at least 48 h. Taste acceptance was also assessed. There was no statistically significant difference between the two contrast media with regard to the primary and secondary efficacy variables assessed, although higher ratings were observed for iodixanol. The 100 mm VAS score overall was 86 mm for iodixanol and 82 mm for iohexol (95% confidence interval -2.56, 10.42). The frequency of adverse events was lower for patients receiving iodixanol. Adverse events, mainly diarrhoea, occurred in 12 patients (16.2%) in the iodixanol group and 28 patients (35.9%) in the iohexol group. This reached statistical significance (p=0.006). Overall, iodixanol is well suited for examinations of the gastrointestinal tract, giving good efficacy results and fewer adverse events than iohexol.

[Decline of violence in ]rhus. Violence registered in ]rhus hospital during a period of 12 years]. / Faldende vold i Arhus.

The aim of this study was to describe the changes in frequency and character of interpersonal violence in Aarhus during a twelve year period. A one year (1993-1994) prospective registration of all persons exposed to violence and attending the casualty wards or the Department of Forensic Medicine was performed. The results were compared with similar studies performed in 1981-1982 and 1987-1988. The incidence in the last one year period had decreased significantly to 5.5 cases/1000 inhabitants compared to 6.5 in 1981-1982 and 7.5 in 1987-1988. The decrease was most distinct among men between 15-24 years of age. Ninety percent of the lesions were minor and the severity did not differ from the former study. Among risk factors associated to severe violence were men between 25-49 years of age, foreigners, use of knives and domestic violence. Firearms were only involved in 0.8% of the cases. Significantly higher proportion of the victims reported the incidence to the police in 1993-1994 than previously.