[Childhood abuse experiences and chronic low back pain. Direct and mediated effects of childhood abuse in different pain dimensions of nonspecific chronic low back pain]. / Frühe Missbrauchserlebnisse bei chronischem Kreuzschmerz. Direkte und mediierte Effekte früher Missbrauchserlebnisse auf verschiedene Schmerzdimensionen chronischer nichtspezifischer Kreuzschmerzen.

BACKGROUND: Physical, sexual and emotional abuse in childhood and adolescence is considered to play a role in the etiology and generalization of chronic pain in adulthood. However, it remains unclear whether abuse is specifically associated with different dimensions of nonspecific chronic low back pain (CLBP) and if these associations are mediated by psychological symptoms. MATERIAL AND METHODS: A total of 103 patients with validated CLBP were assessed by pain drawing, the multidimensional pain questionnaire and the pain experience scale. The childhood trauma questionnaire was used to retrospectively screen for physical, sexual and emotional abuse in childhood and adolescence. Patients were also screened for symptoms of depression, anxiety and dissociation in order to look for possible mediators. RESULTS: Patients with CLBP who reported childhood abuse showed higher pain intensity, higher spatial extent of pain, higher affective and sensory pain sensation and more pain disability compared to CLBP patients who had not experienced abuse. However, multivariate analyses revealed that only the spatial extent of pain was directly associated with childhood abuse. Furthermore, a significant association between childhood abuse and sensory pain sensation was found to be mediated by symptoms of anxiety and dissociation. CONCLUSION: The influence of childhood abuse on CLBP is different for specific pain dimensions; therefore, CLBP should be faced as a complex construct that comprises different dimensions. Childhood abuse is suggested as a risk factor for spreading pain in CLBP persons; therefore, CLBP patients reporting additional pain locations might benefit from diagnostic and therapeutic interventions specific for childhood abuse experiences.

Quality of interhospital transport of the critically ill: impact of a Mobile Intensive Care Unit with a specialized retrieval team.

INTRODUCTION: In order to minimize the additional risk of interhospital transport of critically ill patients, we started a mobile intensive care unit (MICU) with a specialized retrieval team, reaching out from our university hospital-based intensive care unit to our adherence region in March 2009. To evaluate the effects of this implementation, we performed a prospective audit comparing adverse events and patient stability during MICU transfers with our previous data on transfers performed by standard ambulance. METHODS: All transfers performed by MICU from March 2009 until December 2009 were included. Data on 14 vital variables were collected at the moment of departure, arrival and 24 hours after admission. Variables before and after transfer were compared using the paired-sample T-test. Major deterioration was expressed as a variable beyond a predefined critical threshold and was analyzed using the McNemar test and the Wilcoxon Signed Ranks test. Results were compared to the data of our previous prospective study on interhospital transfer performed by ambulance. RESULTS: A total of 74 interhospital transfers of ICU patients over a 10-month period were evaluated. An increase of total number of variables beyond critical threshold at arrival, indicating a worsening of condition, was found in 38 percent of patients. Thirty-two percent exhibited a decrease of one or more variables beyond critical threshold and 30% showed no difference. There was no correlation between patient status at arrival and the duration of transfer or severity of disease. ICU mortality was 28%. Systolic blood pressure, glucose and haemoglobin were significantly different at arrival compared to departure, although significant values for major deterioration were never reached. Compared to standard ambulance transfers of ICU patients, there were less adverse events: 12.5% vs. 34%, which in the current study were merely caused by technical (and not medical) problems. Although mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was significantly higher, patients transferred by MICU showed less deterioration in pulmonary parameters during transfer than patients transferred by standard ambulance. CONCLUSIONS: Transfer by MICU imposes less risk to critically ill patients compared to transfer performed by standard ambulance and has, therefore, resulted in an improved quality of interhospital transport of ICU patients in the north-eastern part of the Netherlands.

A phase I study of AMD473 and docetaxel given once every 3 weeks in patients with advanced refractory cancer: a National Cancer Institute of Canada-Clinical Trials Group trial, IND 131.

BACKGROUND: AMD473 (previously ZD0473) is a new-generation platinum compound with activity against a wide range of human tumour cell lines and xenografts, including carboplatin- and cisplatin-resistant lines. To assess its potential combined with a taxane, a phase I study of AMD473 and docetaxel in advanced cancer was initiated by the National Cancer Institute of Canada-Clinical Trials Group. PATIENTS AND METHODS: Patients with advanced cancer, measurable disease, performance status Eastern Cooperative Oncology Group 0-2, no major organ dysfunction, and one or no previous taxane regimen received escalating doses of AMD473 and docetaxel every 3 weeks, with a starting dose of AMD473 80 mg/m(2) and docetaxel 60 mg/m(2). RESULTS: Thirty-three patients enrolled on four dose levels were evaluable for toxicity and 25 patients were evaluable for response. The maximum tolerated dose was dose level 4 (AMD473 120 mg/m(2) and docetaxel 75 mg/m(2)), with grade 4 neutropenia in both minimally and heavily pretreated patients causing dose-limiting toxicity. As well at dose level 4, one patient had grade 3 vomiting despite premedication. Dose level three was expanded for both groups of patients and was defined as the recommended phase II dose at AMD473 100 mg/m(2) and docetaxel 75 mg/m(2). Non-hematologic toxicities included fatigue, diarrhoea and other mild toxicities. There was one partial response in a patient with prostate cancer and stable disease in 15 patients. No apparent pharmacokinetic interaction was noted. CONCLUSION: AMD473 and docetaxel can be combined with a recommended phase II dose level of 100 mg/m(2) and 75 mg/m(2), respectively, given intravenously every 3 weeks. The combination has activity and should be explored in responsive tumour types.

Absence of Peyer's patches and abnormal lymphoid architecture in chronic proliferative dermatitis (cpdm/cpdm) mice.

The chronic proliferative dermatitis (cpdm) mutation causes inflammation in multiple organs, most prominently in the skin. Examination of the immune system revealed severe abnormalities in the architecture of lymphoid tissues. Peyer's patches were absent. In contrast, the spleen, lymph nodes, and nasal-associated lymphoid tissues were present. The spleen had normal numbers of T and B cells, but the spleen, lymph nodes, and nasal-associated lymphoid tissues had poorly defined follicles and lacked germinal centers and follicular dendritic cells. The marginal zone in the spleen was absent. The total concentration of serum IgG, IgA, and IgE in cpdm/cpdm mice was significantly decreased, whereas serum IgM was normal. Fecal IgA was low to undetectable in mutant mice, and the concentration of fecal IgM was increased. The titer of DNP-specific Abs following immunization with DNP-keyhole limpet hemocyanin was significantly decreased for all IgG subclasses. In contrast, T cell function appeared normal as assessed by evaluation of the contact hypersensitivity response in cpdm/cpdm mice. The cpdm mutation causes a complex phenotype that is characterized by multiorgan inflammation and the defective development of lymphoid tissues. The cpdm/cpdm mouse may be a useful model to study the factors that control the development of lymphoid tissues, in particular the Peyer's patches, and the mechanisms that control the humoral immune response.

Computer determination of perfusion patterns in pulmonary capillary networks.

Individual pulmonary capillaries are not steadily perfused. By using in vivo microscopy, it can readily be demonstrated that perfusion continually switches between capillary segments and between portions of the network within a single alveolar wall. These changes in capillary perfusion occur even when upstream pressure and flow are constant. Flow switching between capillary segments in the absence of hemodynamic changes in large upstream vessels suggests that capillary perfusion patterns could be random. To calculate the probability that perfusion patterns could occur by chance, it is necessary to know the total number of possible perfusion patterns in a given capillary network. We developed a computer program that can determine every possible perfusion pattern for any given capillary network, and from that information we can calculate whether perfusion of individual segments in the network is random. With the results of the computer program, we have obtained statistical evidence that some capillary segments in a network are nonrandomly perfused.

Effects of CLIP (corticotropin-like intermediate lobe peptide) and CLIP fragments on paradoxical sleep in rats.

The effects of the POMC-derived peptide CLIP [corticotropin-like intermediate lobe peptide; ACTH(18-39)] and its shorter fragments ACTH(25-39), ACTH(18-24), and ACTH(20-24) on sleep were investigated in rats housed under normal 12-h light/12-h dark conditions (0600 light on). CLIP (10 ng) or equimolar doses of CLIP fragments, respectively, were injected intracerebroventricularly immediately before the 8-h recording period (0800-1600). It was found that paradoxical sleep (PS) was increased by CLIP (+20%) as well as by the N-terminal CLIP fragment ACTH(18-24) (+18%) and by the pentapeptide ACTH(20-24) (+25%), whereas the C-terminal fragment ACTH(25-39) was ineffective. Slow-wave sleep (SWS) was not influenced. These results clearly demonstrate that CLIP and its N-terminal fragments have selective PS-enhancing effects. CLIP and/or CLIP partial sequences are possible candidates for endogenous PS-inducing peptides involved in the physiological regulation of paradoxical sleep.

Computer simulation of neutrophil transit through the pulmonary capillary bed.

One-half of the neutrophils that enter the pulmonary circulation become temporarily trapped in capillaries. The neutrophils that are impeded make complete stops between free-flowing movements. These observations, based on in vivo microscopy, suggest that pulmonary margination is caused by neutrophils being impeded at focal sites in the capillary bed. To investigate the frequency with which impeding sites had to occur in the pulmonary capillaries to trap one-half of the circulating neutrophils, we developed a computer model to simulate neutrophils encountering discrete obstructions in a capillary-like network. Surprisingly, if only 1% of the capillaries in the network acted as traps, one-half of the neutrophils stopped at least once. The trapping ability of a given percentage of obstructions was independent both of the geometry of the network was whether the obstructions occurred in the segments or junctions. To simulate neutrophil transit more realistically, both neutrophil and capillary diameters were randomly selected from published diameter distributions. Every neutrophil was trapped multiple times by this model, suggesting that cell deformation contributes importantly to neutrophil passage through the pulmonary capillary bed.

Neutrophil kinetics in the pulmonary microcirculation. Effects of pressure and flow in the dependent lung.

Increases in pulmonary arterial pressure or blood flow raise peripheral white cell count by releasing sequestered leukocytes from the lung. The effects of altered hemodynamics, however, on the leukocyte sequestration site and on the distribution of leukocyte transit times through the pulmonary microcirculation are unknown. We used in vivo fluorescence videomicroscopy to study the passage of individual, fluorescein-isothiocyanate-labeled neutrophils through the pulmonary microcirculation of anesthetized dogs. Pulmonary hemodynamics were altered over a wide range. Regardless of the hemodynamic conditions, the only place that any of the 2,919 observed neutrophils stopped was in the capillaries. The periods of immobility had a wide range, from less than 1 to greater than 1,200 s. Because the cells remained motionless once they stopped and then accelerated suddenly as they regained the free-flowing stream, the obstructions must have been discrete. About a quarter of the capillary pathways had one site of high resistance. Another quarter offered two or more obstructions. In the remaining half, the neutrophils passed rapidly and without pause from arteriole to venule. Increases in pressure and flow decreased the number of times that individual cells stopped. These changes altered the median transit time by shifting the distribution of transit times between the slowest and fastest groups. We conclude that most of the total pathlength of perfused capillaries offers little resistance even to neutrophils. There are, however, focal areas in individual capillaries that offer high resistance to neutrophil passage.