Pollen-based quantitative reconstructions of Holocene regional vegetation cover (plant-functional types and land-cover types) in Europe suitable for climate modelling.

We present quantitative reconstructions of regional vegetation cover in north-western Europe, western Europe north of the Alps, and eastern Europe for five time windows in the Holocene [around 6k, 3k, 0.5k, 0.2k, and 0.05k calendar years before present (bp)] at a 1° × 1° spatial scale with the objective of producing vegetation descriptions suitable for climate modelling. The REVEALS model was applied on 636 pollen records from lakes and bogs to reconstruct the past cover of 25 plant taxa grouped into 10 plant-functional types and three land-cover types [evergreen trees, summer-green (deciduous) trees, and open land]. The model corrects for some of the biases in pollen percentages by using pollen productivity estimates and fall speeds of pollen, and by applying simple but robust models of pollen dispersal and deposition. The emerging patterns of tree migration and deforestation between 6k bp and modern time in the REVEALS estimates agree with our general understanding of the vegetation history of Europe based on pollen percentages. However, the degree of anthropogenic deforestation (i.e. cover of cultivated and grazing land) at 3k, 0.5k, and 0.2k bp is significantly higher than deduced from pollen percentages. This is also the case at 6k in some parts of Europe, in particular Britain and Ireland. Furthermore, the relationship between summer-green and evergreen trees, and between individual tree taxa, differs significantly when expressed as pollen percentages or as REVEALS estimates of tree cover. For instance, when Pinus is dominant over Picea as pollen percentages, Picea is dominant over Pinus as REVEALS estimates. These differences play a major role in the reconstruction of European landscapes and for the study of land cover-climate interactions, biodiversity and human resources.

[Oral osmotic hydromorphone (OROS) in patients with chronic severe pain due to osteoarthritis under daily routine conditions]. / OROS-hydromorphon bei starken chronischen Arthroseschmerzen. Einsatz unter klinischen Routinebedingungen.

OBJECTIVE: Objective of this prospective, non-interventional study was to obtain data under a therapy with oral osmotic hydromorphone (OROS) in patients with chronic severe pain due to osteoarthritis under daily routineconditions. METHOD: Using the Brief Pain Inventory (BPI) patients assessed pain relief as well as the impact of pain on activities of daily living. Pain control, treatment satisfaction (by patient and investigator), physical therapy capability and the WOMAC-Index (Western Ontario and McMaster Universities Osteoarthritis) were additionally evaluated. Adverse events were continuously monitored throughout the study. RESULTS: 206 patients with chronic severe pain due to osteoarthritis and an initial pain intensity of 6 (NRS 0-10) received oral OROS-hydromorphone for three months. Under this treatment pain relief as well as the impact of pain on activities of daily living improved significantly. At the last examination, the patients reported a mean pain reduction of 2.5 (rest)/3.0 (movement) by day and of 2.6 (rest)/3.1 (movement) bynight (p < 0.0001). The very good pain control was accompanied by a high treatment satisfaction and an improved sleep quality. Physical therapy capability improved in 77.9% of the patients, the WOMAC index as indicator of pain and function in osteoarthritis decreased significantly from 13.3 (baseline) to 7.5 (V6). The most frequently reported adverse events were obstipation, nausea, dizziness and fatigue. 17.5% of the patients cut the study short because of adverse events. CONCLUSION: The treatment of patients with chronic pain due to osteoarthritis with oral osmotic hydromorphone resulted in a significant reduction of all documented pain related assessments.

Assessing cognition and psychomotor function under long-term treatment with controlled release oxycodone in non-cancer pain patients.

BACKGROUND: The therapeutic use of opioids can be associated with altered cognition and impaired psychomotor function. Several studies have demonstrated the impact of opioid therapy on psychomotor performance and cognition, but no data exist about the effect of long-term treatment with controlled release oxycodone (CRO) on driving ability. METHODS: Thirty patients suffering from chronic non-cancer pain who had been treated with stable doses of CRO where included in a prospective trial and compared with 90 healthy volunteers (matched pairs). A computerized test battery that was developed to assess the driving ability of traffic delinquents in Germany was employed. Attention reaction, visual orientation, motor coordination and vigilance were evaluated. The data from a total of 11 parameters were assessed and for each test a relevant score was defined. As the primary endpoint the sum score of the three relevant scores was determined. A weaker statistical means to assess the patients' performance is to compare the test results with an age-independent control group. Individuals performing worse than the 16th percentile of this control group are considered to be unable to drive according to German legislation. RESULTS: Significant non-inferiority could not be demonstrated for the primary endpoint. However, driving ability as defined as a result above the 16th percentile did not differ significantly between the patients receiving CRO and the age-independent control group. CONCLUSION: The use of CRO does not prohibit driving, but individual assessment is necessary.

[Central pain processing in chronic low back pain. Evidence for reduced pain inhibition]. / Zentrale Schmerzverarbeitung bei chronischem Rückenschmerz. Hinweise auf verminderte Schmerzinhibition.

INTRODUCTION: A study of patients with low back pain (LBP) had revealed altered central pain processing. At an equal pain level LBP patients had considerably more neuronal activation in the somatosensory cortices than controls. In a new analysis of this dataset, we further investigated the differences in central pain processing between LBP patients and controls, looking for possible pathogenic mechanisms. METHODS: Central pain processing was studied by functional magnetic resonance imaging (fMRI), using equally painful pressure stimuli in a block paradigm. In this study, we reanalyzed the fMRI data to statistically compare pain-elicited neuronal activation of both groups. RESULTS: Equally painful pressure stimulation resulted in a significantly lower increase of regional cerebral blood flow (rCBF) in the periaqueductal gray (PAG) of the LBP patients. The analysis further revealed a significantly higher increase of rCBF in LBP than in HC in the primary and secondary somatosensory cortex and the lateral orbitofrontal cortex (LOFK), elicited by these same stimuli. CONCLUSIONS: These findings support a dysfunction of the inhibitory systems controlled by the PAG as a possible pathogenic mechanism in chronic low back pain.

[Oral controlled-release oxycodone for the treatment of chronic pain. Data from 4196 patients]. / Therapie chronischer Schmerzen mit oralem retardiertem Oxycodon. Behandlungsdaten von 4196 Patienten.

Oral controlled-release oxycodone has been available for the treatment of chronic pain in Germany since 1998. Controlled trials have shown good clinical efficacy and tolerability. This survey reports results from six open prospective multicenter trials. In these trials 4196 patients suffering from cancer pain and non-cancer-related pain with inadequate pain relief were treated with oral controlled-release oxycodone for 3-4 weeks. Only a few participating physicians were pain specialists. A total of 356 patients suffering from pain of the musculoskeletal system and receiving oxycodone therapy were monitored for 6 months. Exclusion from the studies was due mainly to inadequate analgesia, side effects, and noncompliance. The efficacy of oxycodone was rated to be better than moderate by most of the patients, quality of life parameters increased significantly, and patient satisfaction was high. The treatment with oral controlled-release oxycodone was a safe and effective option even when used by nonspecialized physicians.

Pain catastrophizing and neural responses to pain among persons with fibromyalgia.

Pain catastrophizing, or characterizations of pain as awful, horrible and unbearable, is increasingly being recognized as an important factor in the experience of pain. The purpose of this investigation was to examine the association between catastrophizing, as measured by the Coping Strategies Questionnaire Catastrophizing Subscale, and brain responses to blunt pressure assessed by functional MRI among 29 subjects with fibromyalgia. Since catastrophizing has been suggested to augment pain perception through enhanced attention to painful stimuli, and heightened emotional responses to pain, we hypothesized that catastrophizing would be positively associated with activation in structures believed to be involved in these aspects of pain processing. As catastrophizing is also strongly associated with depression, the influence of depressive symptomatology was statistically removed. Residual scores of catastrophizing controlling for depressive symptomatology were significantly associated with increased activity in the ipsilateral claustrum (r = 0.51, P < 0.05), cerebellum (r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.47, P < 0.05), and parietal cortex (r = 0.41, P < 0.05), and in the contralateral dorsal anterior cingulate gyrus (ACC; r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.41, P < 0.05), medial frontal cortex (r = 0.40, P < 0.05) and lentiform nuclei (r = 0.40, P < 0.05). Analysis of subjects classified as high or low catastrophizers, based on a median split of residual catastrophizing scores, showed that both groups displayed significant increases in ipsilateral secondary somatosensory cortex (SII), although the magnitude of activation was twice as large among high catastrophizers. Both groups also had significant activations in contralateral insula, SII, primary somatosensory cortex (SI), inferior parietal lobule and thalamus. High catastrophizers displayed unique activation in the contralateral anterior ACC, and the contralateral and ipsilateral lentiform. Both groups also displayed significant ipsilateral activation in SI, anterior and posterior cerebellum, posterior cingulate gyrus, and superior and inferior frontal gyrus. These findings suggest that pain catastrophizing, independent of the influence of depression, is significantly associated with increased activity in brain areas related to anticipation of pain (medial frontal cortex, cerebellum), attention to pain (dorsal ACC, dorsolateral prefrontal cortex), emotional aspects of pain (claustrum, closely connected to amygdala) and motor control. These results support the hypothesis that catastrophizing influences pain perception through altering attention and anticipation, and heightening emotional responses to pain. Activation associated with catastrophizing in motor areas of the brain may reflect expressive responses to pain that are associated with greater pain catastrophizing.

Failure of autologous fresh frozen plasma to reduce blood loss and transfusion requirements in coronary artery bypass surgery.

BACKGROUND: Previous studies failed to demonstrate any benefit from prophylaxis with fresh frozen plasma (FFP) after cardiopulmonary bypass (CPB). The results, however, were limited by either retrospective study design or use of FFP in subtherapeutic doses (2-3 units). The authors evaluated whether a therapeutic dose (15 ml/kg) of FFP reduces blood loss and transfusion requirements in elective coronary artery bypass surgery. The risks of multiple allogeneic blood donor exposure were circumvented by using autologous plasma. METHODS: Sixty adult patients scheduled for elective primary coronary artery bypass grafting were randomized to receive, after CPB, an intravenous infusion of 15 ml/kg of either autologous FFP (30 patients) or 6% hydroxyethyl starch 450/0.7 (HES; 30 patients). Autologous plasma was obtained by platelet-poor plasmapheresis several weeks before surgery. Perioperative blood transfusions were administered per protocol. Postoperative blood loss was defined as the chest tube drainage during the first 24 h after surgery. RESULTS: The data from 56 patients (FFP group, 27 patients; HES group, 29 patients) who completed the study according to protocol were analyzed. Median postoperative blood loss was 630 ml (range, 450-1,840 ml) and 830 ml (range, 340-1,980 ml) in the FFP and HES groups, respectively (P = 0.08). Both postoperative (0-24 h) and total perioperative erythrocyte transfusion requirements did not differ significantly between the groups (P = 0.32 and 0.14, respectively). CONCLUSION: The prophylactic administration of a therapeutic dose (15 ml/kg) of autologous FFP after CPB failed to reduce blood loss and transfusion requirements in patients undergoing uncomplicated, elective, primary coronary artery bypass surgery.

A hemisphere array for non-invasive ultrasound brain therapy and surgery.

Ultrasound phased arrays may offer a method for non-invasive deep brain surgery through the skull. In this study a hemispherical phased array system is developed to test the feasibility of trans-skull surgery. The hemispherical shape is incorporated to maximize the penetration area on the skull surface, thus minimizing unwanted heating. Simulations of a 15 cm radius hemisphere divided into 11, 64, 228 and 512 elements are presented. It is determined that 64 elements are sufficient for correcting scattering and reflection caused by trans-skull propagation. An optimal operating frequency near 0.7 MHz is chosen for the array from numerical and experimental thermal gain measurements comparing the power between the transducer focus and the skull surface. A 0.665 MHz air-backed PZT array is constructed and evaluated. The array is used to focus ultrasound through an ex vivo human skull and the resulting fields are measured before and after phase correction of the transducer elements. Finally, to demonstrate the feasibility of trans-skull therapy, thermally induced lesions are produced through a human skull in fresh tissue placed at the ultrasound focus inside the skull.

Multiple system reaction to trimethoprim-sulfamethoxazole.

Trimethoprim-sulfamethoxazole may cause life-threatening reactions and even death, but such reactions are rare and do not detract from its usefulness. As with any therapy, however, caution should be observed in its use in children, and especially in the elderly.