Characterization of a novel capsaicin/heat ongoing pain model.

BACKGROUND: Human experimental pain models provide an important translational link between pre-clinical models and clinical pain. Using topical capsaicin and continuous heat application, the novel capsaicin/heat ongoing pain (CHOP) model induces long-lasting experimental pain of which the perceived intensity can be individually adjusted. METHODS: In the CHOP model, capsaicin or control cream is applied to a 10 × 10 cm skin area and a heating pad is applied over the area after cream removal. Two experiments in healthy participants were performed for model characterization. In Experiment 1, a constant temperature was applied for 60 min; in Experiment 2, temperature was adjusted to maintain a constant perceived intensity for 60 min. RESULTS: Experiment 1: across participants, constant temperature induced initial habituation followed by an increase in sensation back to baseline. Cluster analysis revealed that half the participants sensitized to the constant temperature, while the other half did not. The degree of sensitization was related to the baseline pain unpleasantness, relative to pain intensity. Experiment 2: constant perceived intensity was achieved in the painful and a non-painful control condition. The two conditions did not differ regarding possibly confounding variables, including blood pressure, heart rate, inflammation or physiological stress as measured by surrogate markers. Secondary allodynia and hyperalgesia were reported more following painful compared to control stimulation. Sensitizers as determined in Experiment 1 were also more pain sensitive in Experiment 2. CONCLUSION: The CHOP model reproduces some aspects of clinical pain, such as longer duration, sensitization, secondary allodynia and hyperalgesia. SIGNIFICANCE: Here we demonstrate a novel pain model that can be applied for up to an hour without tissue damage. The CHOP model allows for investigation of primary and secondary hyperalgesia as well as top-down influences on sensitization, thereby providing an experimental model that can be used to assess clinically-oriented questions.

Relationships between the cytotoxic effects of restriction endonucleases and radiation on mammalian cells.

Wild-type Chinese hamster ovary (CHO) cells, a radiosensitive mutant CHO line (xrs6), and two human cervical carcinoma cell lines, MS751 and ME180, differ in sensitivity to ionizing radiation with surviving fractions at 2 Gy (SF2) of 0.84, 0.06, 0.90 and 0.24 respectively. Restriction endonucleases (REs) were introduced into the cells by treatment with streptolysin O (SLO) and the effects of this on clonogenic cell survival were compared. A comparison was made of REs inducing either blunt- (AluI) or cohesive-ended (Sau3AI) double-strand breaks. Whilst MS751 cells were resistant to the effects of both REs, AluI caused significantly greater cell killing than Sau3AI in the other three lines (p < 0.05 for all). Both ME180 and xrs6 were significantly more sensitive to REs than their radioresistant counterparts, MS751 and CHO (p < 0.05 for both). In order to investigate the effect of DNA methylation on dsb induction, the isoschizomers MspI and HpaII (cohesive-ended dsb inducers) were introduced into the cell lines. Both REs recognize the same sequence but HpaII cannot cleave if the internal cytosine is methylated. MS751 was also resistant to the effects of both of these enzymes and MspI was more cytotoxic than HpaII in the other three lines (p < 0.03 for all). The differential sensitivity to the two REs was more marked in the radiosensitive cell lines, suggesting that there may be a greater degree of DNA methylation in radiosensitive cells. The variation in sensitivities to REs between the cell lines could not be explained in terms of differences in cell poration following SLO treatment because, although MS751 was resistant to SLO (25% of cells porated), the other three lines showed the same level of cell poration (98% of cells). With these four cell lines, there was a significant correlation between sensitivity to RE and radiosensitivity for AluI, Sau3AI and MspI but not for HpaII.

The role of excess subcutaneous fat in pain and sensory sensitivity in obesity.

BACKGROUND: Previous studies suggest pain sensitivity may be decreased in obesity, but it is unknown whether this is a global or a site-specific phenomenon related to the amount of excess fat. DESIGN: a cross-sectional study comparing obese and non-obese participants on body sites with much and little excess subcutaneous fat in obesity. Hot and cold sensory detection thresholds, pain thresholds, pain tolerance and subjective ratings for a cold (0 °C) and hot (48 °C) stimulus were assessed using a 16 × 16 mm thermode (Medoc, Israel) on the forehead and abdomen. Pressure pain thresholds were measured on the hand. Cold water immersion tolerance duration and subjective ratings were assessed on the hand. Two indices of central pain processing, i.e., temporal summation and heterotopic noxious stimulation, were assessed. RESULTS: A total of 20 obese participants [10M/10F, BMI mean (SD) =41.5 kg/m(2) (9.4 kg/m(2) )] and 20 age- and gender-matched non-obese controls [10M/10F, BMI mean (SD) =23.5 kg/m(2) (2.9 kg/m(2) )] were studied. Compared with non-obese, obese participants had higher thresholds and lower subjective ratings, indexing decreased sensitivity, for painful and non-painful thermal stimuli on the abdomen, an area with much excess subcutaneous fat. Decreases in abdominal sensitivity correlated with measures of adiposity (i.e., waist-to-hip ratio and subcutaneous fat thickness). On areas with little excess subcutaneous fat (forehead and hand), obese and non-obese groups did not differ in measures of thermal or pressure sensitivity, nor for indices of central pain processing. CONCLUSION: Obese participants are less sensitive than non-obese individuals, but only on areas with excess subcutaneous fat.

Enabling GeneHunter as a grid service: a case study for implementing analytical services in biomedical grids.

BACKGROUND: A cursory analysis of the biomedical grid literature shows that most projects emphasize data sharing and the development of new applications for the grid environment. Much less is known about the best practices for the migration of existing analytical tools into the grid environment. OBJECTIVES: To make GeneHunter available as a grid service and to evaluate the effort and best practices needed to enable a legacy application as a grid service when addressing semantic integration and using the caBIG tools. METHODS: We used the tools available in the caBIG environment because these tools are quite general and they may be used to deploy services in similar biomedical grids that are OGSA-compliant. RESULTS: We achieved semantic integration of GeneHunter within the caBIG by creating a new UML model, LinkageX, for the LINKAGE data format. The LinkageX UML model has been published in the caDSR and it is publically available for usage with GeneHunter or any other program using this data format. CONCLUSIONS: While achieving semantic interoperability is still a time-consuming task, the tools available in caBIG can greatly enhance productivity and decrease errors.

Longitudinal changes in extended roles in radiography: A new perspective.

PURPOSE: The purpose of this research was to update data on the scope of changes to radiographic practice since the principal author's last survey in 2000. The study also sought to identify any regional patterns in the adoption and diffusion of extended roles and to map the implementation of the 4-tier structure. METHOD: Structured questionnaires were sent to radiology managers at acute National Health Service (NHS) trusts across the United Kingdom. Information sought included region, teaching/non-teaching status, the nature of extended role tasks undertaken and the year in which these tasks were adopted, numbers of radiographers and radiologists in post. Information was also sought on the implementation of the '4-tier structure'. RESULTS: Some 177 questionnaires were returned from a total of 258 dispatched giving a 68.6% response rate. In 166 trusts, radiographers administered intravenous injections; they performed barium enemas in 147 trusts and barium meals in 19 trusts, while a red dot system was in operation in 143 trusts. Each category showed an increase from that reported in 2000. Likewise reporting by radiographers had increased since 2000. Responses indicated that at 146 trusts, radiographers were reporting in ultrasound; reporting of the appendicular skeleton was undertaken at 81 trusts and axial skeletal reporting at 70 trusts. Barium enemas were reported by radiographers in 78 trusts. Reporting was also undertaken by radiographers on barium meals, mammography, nuclear medicine, paediatric and chest radiography; and all showed an increase in frequency since 2000. Regional differences were again apparent in reporting, with a greater prevalence in the English regions, with the exception of London. In respect of the 4-tier structure, 59% of the sample employed assistant practitioners, 47% advanced practitioners and 3% employed consultants. The numbers reported in each category (excluding practitioners) were 158 assistants, 623 advanced practitioners and six consultants. There were a number of trusts that had plans to introduce assistants, advanced practitioners and/or consultants over the following two-year period. CONCLUSION: The study provided data that illustrated the extent to which NHS acute trusts are utilising the skills of radiographers and recognizing the extended scope of radiographic practice. Implementation of the 4-tier structure is underway with the greatest number of staff (excluding practitioners) categorized as advanced practitioners. This does provide some evidence of trusts responding to the 2000 NHS Plan in introducing new ways of working. The number of consultants, as could be expected at the time of the survey was low.

Allergen-induced glycoconjugate secretion in guinea-pig trachea in vivo: modulation by indomethacin, BW B70C and ZD-2138.

A method has been established for measurement of tracheal secretions in anaesthetized, ventilated guinea-pigs. The upper trachea was cannulated and perfused with saline. The perfusate was analysed for protein using the Lowry assay and for glycoconjugates ('mucus') by a procedure generating a fluorophore from fucose moieties in the sample. Intravenously infused acetylcholine (ACh) stimulated an increase in glycoconjugate secretion which was maximal after 75 min of ACh administration. Total protein concentration was not increased. Intravenously infused 15-HETE produced a similar increase in glycoconjugate secretion also without increasing protein concentration, but the time of maximal effect was earlier (30 min) than with ACh. Intravenous infusion of allergen (ovalbumin) in antihistamine pretreated, sensitized animals induced a dose-related glycoconjugate secretion which was maximal at 30 min after challenge. Indomethacin potentiated allergen-induced glycoconjugate secretion. The reportedly specific inhibitor of 5-lipoxygenase, ZD-2138, substantially inhibited allergen-induced pulmonary bronchoconstriction but did not influence glycoconjugate secretion. In contrast, the selective 5-, 15-lipoxygenase inhibitor BW B70C significantly attenuated both allergic airway closure and glycoconjugate secretion. These studies demonstrate the practicability of measuring glycoconjugate secretion in guinea-pig trachea in vivo, and that ACh and 15-HETE are potent secretagogues in this species. Further, they suggest that allergic glycoconjugate secretion is mediated, at least in part, via the release of lipid mediators from pathways other than via 5-lipoxygenase.

Raised respiratory rate in elderly patients: a valuable physical sign.

Measurements of respiratory rate in 82 long-stay patients aged 67-101 years yielded a normal range of 16-25 breaths a minute. In a prospective study of 60 consecutive acute admissions to a geriatric unit, 19 out of 21 patients diagnosed as lower respiratory tract infections had respiratory rates above the upper limit of normal on the day of diagnosis; the rise in respiratory rate preceded the clinical diagnosis. All eight patients who were diagnosed on admission as having a lower respiratory tract infection had a respiratory rate greater than 26, with a mean of 29.7 breaths a minute. Patients admitted for other conditions-for example, urinary tract infection-rarely had respiratory rates outside the normal range. Accurate measurement of respiratory rate is a valuable diagnostic aid in elderly patients.