Exploring experiences and understandings of pain in adults with intellectual disabilities.

BACKGROUND: People with intellectual disabilities (ID) are at risk that their health problems, many of which cause pain, go unrecognised and untreated. Their understanding and personal experiences of pain have received little research attention. METHOD: Information was collected from 15 adults with ID using semi-structured interviews about their experiences and understanding of pain. Transcripts were analysed using content analysis. RESULTS: Participants described pain using negative meanings and strong imagery, with various causes of pain suggested, but said little about how they coped with pain. Participants varied in whether they reported pains to carers, some choosing to hide the experience. There seemed a general belief that others can tell when someone is in pain. CONCLUSIONS: Conversations regarding pain with adults with ID are a real challenge; health-care staff need to think carefully about the questions they ask. Possessing verbal skills cannot be taken as an indication that pain will be communicated.

Increasing doxorubicin activity against breast cancer cells using PPARγ-ligands and by exploiting circadian rhythms.

BACKGROUND AND PURPOSE: Doxorubicin is effective against breast cancer, but its major side effect is cardiotoxicity. The aim of this study was to determine whether the efficacy of doxorubicin on cancer cells could be increased in combination with PPARγ agonists or chrono-optimization by exploiting the diurnal cycle. EXPERIMENTAL APPROACH: We determined cell toxicity using MCF-7 cancer cells, neonatal rat cardiac myocytes and fibroblasts in this study. KEY RESULTS: Doxorubicin damages the contractile filaments of cardiac myocytes and affects cardiac fibroblasts by significantly inhibiting collagen production and proliferation at the level of the cell cycle. Cyclin D1 protein levels decreased significantly following doxorubicin treatment indicative of a G1/S arrest. PPARγ agonists with doxorubicin increased the toxicity to MCF-7 cancer cells without affecting cardiac cells. Rosiglitazone and ciglitazone both enhanced anti-cancer activity when combined with doxorubicin (e.g. 50% cell death for doxorubicin at 0.1 µM compared to 80% cell death when combined with rosiglitazone). Thus, the therapeutic dose of doxorubicin could be reduced by 20-fold through combination with the PPARγ agonists, thereby reducing adverse effects on the heart. The presence of melatonin also significantly increased doxorubicin toxicity, in cardiac fibroblasts (1 µM melatonin) but not in MCF-7 cells. CONCLUSIONS AND IMPLICATIONS: Our data show, for the first time, that circadian rhythms play an important role in doxorubicin toxicity in the myocardium; doxorubicin should be administered mid-morning, when circulating levels of melatonin are low, and in combination with rosiglitazone to increase therapeutic efficacy in cancer cells while reducing the toxic effects on the heart.

What influences midwives in estimating labour pain?

BACKGROUND: Clinicians' estimates of patients' pain are frequently used as a basis for delivering care, and the characteristics of the clinician and of the patient influence this estimate. METHODS: We studied pain estimation by midwives attending women in uncomplicated labour. Sixty-six practising midwives of varied age, ethnicity and professional experience were asked to complete a trait empathy measure and then to estimate the maximum pain and anxiety experienced by six women whose filmed labour contractions they viewed. Additionally, they rated similarity to the labouring women in ethnicity, and described their beliefs about pain expression according to ethnicity. RESULTS: Midwife estimates of pain and anxiety were highly correlated. Longer professional experience was associated with lower pain estimates, while more births to the midwife herself was associated with higher pain estimates. A multiple regression model identified number of births to the midwife herself, and two components of empathy (perspective taking and identification), to be important in predicting midwife pain estimates for women in labour. Midwives expressed clear beliefs about women's expression of pain during labour according to ethnicity, but these beliefs were not consistent across midwives, even between midwives of similar ethnicity. CONCLUSION: Midwives' personal characteristics can bias the estimation of pain in woman in labour and therefore influence treatment.

Using graded motor imagery for complex regional pain syndrome in clinical practice: failure to improve pain.

BACKGROUND: There is good evidence from studies conducted in a single-centre research setting for the efficacy of graded motor imagery (GMI) treatment, a complex physiotherapy intervention, to reduce pain in long-standing complex regional pain syndrome (CRPS). However, whether GMI is effective in clinical practice is not established. AIM: To establish whether GMI is effective in clinical practice. METHODS: We undertook a prospective audit of GMI treatment at two UK centres with a special interest in the management of patients with CRPS. All patients received GMI, in conjunction with a range of other 'best practice' physical and psychological interventions. RESULTS: The patients' average pain intensities did not improve with treatment [centre 1: n = 20, pre-post numeric rating scale (NRS) difference 0.6 [confidence interval (CI) -0.3 to 1.5]; centre 2: n = 12, pre-post NRS difference 0.2 (CI: -0.9 to 1.2)]. Patients at centre 1 reported significant functional improvement. Improved performance on left/right judgement replicated in both centres seen in the clinical trials. CONCLUSIONS: The failure of our real-world implementation of GMI suggests that better understanding of both the GMI methodology and its interaction with other treatment methods is required to ensure that GMI research results can be translated into clinical practice. Our results highlight challenges with the translation of complex interventions for chronic pain conditions into clinical practice.

Liposomes and skin: from drug delivery to model membranes.

The early eighties saw the introduction of liposomes as skin drug delivery systems, initially promoted primarily for localised effects with minimal systemic delivery. Subsequently, a novel ultradeformable vesicular system (termed "Transfersomes" by the inventors) was reported for transdermal delivery with an efficiency similar to subcutaneous injection. Further research illustrated that the mechanisms of liposome action depended on the application regime and the vesicle composition and morphology. Ethical, health and supply problems with human skin have encouraged researchers to use skin models. Traditional models involved polymer membranes and animal tissue, but whilst of value for release studies, such models are not always good mimics for the complex human skin barrier, particularly with respect to the stratum corneal intercellular lipid domains. These lipids have a multiply bilayered organization, a composition and organization somewhat similar to liposomes. Consequently researchers have used vesicles as skin model membranes. Early work first employed phospholipid liposomes and tested their interactions with skin penetration enhancers, typically using thermal analysis and spectroscopic analyses. Another approach probed how incorporation of compounds into liposomes led to the loss of entrapped markers, analogous to "fluidization" of stratum corneum lipids on treatment with a penetration enhancer. Subsequently scientists employed liposomes formulated with skin lipids in these types of studies. Following a brief description of the nature of the skin barrier to transdermal drug delivery and the use of liposomes in drug delivery through skin, this article critically reviews the relevance of using different types of vesicles as a model for human skin in permeation enhancement studies, concentrating primarily on liposomes after briefly surveying older models. The validity of different types of liposome is considered and traditional skin models are compared to vesicular model membranes for their precision and accuracy as skin membrane mimics.

Permeation of bioactive constituents from Arnica montana preparations through human skin in-vitro.

This study investigated and characterised transdermal permeation of bioactive agents from a topically applied Arnica montana tincture. Permeation experiments conducted over 48 h used polydimethylsiloxane (silastic) and human epidermal membranes mounted in Franz-type diffusion cells with a methanol-water (50:50 v/v) receptor fluid. A commercially available tincture of A. montana L. derived from dried Spanish flower heads was a donor solution. Further donor solutions prepared from this stock tincture concentrated the tincture constituents 1, 2 and 10 fold and its sesquiterpene lactones 10 fold. Permeants were assayed using a high-performance liquid chromatography method. Five components permeated through silastic membranes providing peaks with relative retention factors to an internal standard (santonin) of 0.28, 1.18, 1.45, 1.98 and 2.76, respectively. No permeant was detected within 12 h of applying the Arnica tincture onto human epidermal membranes. However, after 12 h, the first two of these components were detected. These were shown by Zimmermann reagent reaction to be sesquiterpene lactones and liquid chromatography/diode array detection/mass spectrometry indicated that these two permeants were 11,13-dihydrohelenalin (DH) analogues (methacrylate and tiglate esters). The same two components were also detected within 3 h of topical application of the 10-fold concentrated tincture and the concentrated sesquiterpene lactone extract.

Updated guidelines for the management of Parkinson's disease.

New data on diagnosis, drug therapy, surgery and psychosocial concerns have emerged since the publication of the 1998 Guidelines for the Management of Parkinson's Disease. This article reviews new data and addresses issues left unanswered in the previous guidelines.

Combined phenyl silane and immunoaffinity column cleanup with liquid chromatography for determination of ochratoxin A in roasted coffee: collaborative study.

A collaborative study was conducted to evaluate a liquid chromatography (LC) method for ochratoxin A using sequential phenyl silane and immunoaffinity column cleanup. The method was tested at 3 different levels of ochratoxin A in roasted coffee, which spanned the range of possible future European regulatory limits. The test portion was extracted with methanol and sodium bicarbonate by shaking for 30 min. The extract was filtered, centrifuged, and then cleaned up on a phenyl silane column before being eluted from the washed column with methanol-water. The eluate was diluted with phosphate-buffered saline (PBS) and applied to an ochratoxin A immunoaffinity column, which was washed with water. The ochratoxin A was eluted with methanol, the solvent was evaporated, and the residue was redissolved in injection solvent. After injection of this solution onto a reversed-phase LC apparatus, ochratoxin A was measured by fluorescence detection. Eight laboratory samples of low-level naturally contaminated roasted coffee and 2 laboratory samples of blank coffee (< 0.2 ng/g ochratoxin A at the signal-to-noise ratio of 3:1), along with ampules of ochratoxin A calibrant and spiking solutions, were sent to 15 laboratories in 13 different European countries. Test portions of the laboratory samples were spiked at levels of 4 ng/g ochratoxin A, and recoveries ranged from 65 to 97%. Based on results for spiked blank material (blind duplicates) and naturally contaminated material (blind duplicates at 3 levels), the relative standard deviation for repeatability (RSDr) ranged from 2 to 22% and the relative standard deviation for reproducibility (RSDR) ranged from 14 to 26%. The method showed acceptable within- and between-laboratory precision, as evidenced by HORRAT values, at the low level of determination for ochratoxin A in roasted coffee.

Systematic review of outpatient services for chronic pain control.

AIM OF REPORT. This report reviews the evidence about the effectiveness of treatments for chronic pain. While treatment of chronic pain is usually seen as an integrated service, this report concentrates on the individual interventions that constitute the service. HOW THE RESEARCH WAS CONDUCTED. Searches of databases and journals identified over 15,000 randomised studies with pain as an outcome, and many more which were not randomised. Over 150 systematic reviews relevant to chronic pain treatment were identified and their quality assessed using a simple scoring system. Systematic reviews conducted for this report were based mainly on randomised trials. The number needed to treat (NNT) was chosen as the output for the report. NNTs of 2-4 indicate effective treatments. Because NNT is treatment-specific it overcomes problems associated with highly variable placebo or control event rates in pain trials. Such variability is predominantly due to the limited numbers of patients in the clinical trials. Dichotomous outcome measures are important in synthesising information from many studies, and in deriving NNTs. Methods have been developed which allow mean information on pain relief and intensity to be converted reliably into the simple dichotomous outcome of at least 50% pain relief. RESEARCH FINDINGS. PHYSICAL INTERVENTIONS. Transcutaneous electrical nerve stimulation (TENS) has been shown not to be effective in postoperative and labour pain. In chronic pain, there is evidence that TENS effectiveness increases slowly, and that large doses need to be used. There is lack of evidence for the effectiveness of TENS in chronic pain. There is a lack of evidence for the effectiveness of relaxation. Intravenous systemic regional blockade with guanethidine has been shown to be without effect. Epidural corticosteroids are effective in the short term for back pain and sciatica. Injections of corticosteroids in or around shoulder joints for shoulder pain have been shown not to be effective. There is a lack of evidence supporting spinal cord stimulators. Case series are of poor quality and do not provide evidence of effectiveness, although at least 50% pain relief at 5 years is reported in over 50% of patients. PHARMACOLOGICAL INTERVENTIONS. Minor analgesics are important in chronic pain. NNTs were calculated for analgesics given orally for moderate or severe acute postoperative pain. The NNTs found ranged from 17 (poor) for codeine, 60 mg, to 2.5 (good) for ibuprofen, 400 mg. Anticonvulsant and antidepressant drugs are prescribed for neuropathic pains like diabetic neuropathy. NNTs are of the order of 2.5, showing them to be effective treatments. However, there are too few studies with too few patients to determine which is the best drug. Minor adverse events are common, and major adverse events occur in about 1 in 20 patients. There are no studies comparing antidepressants and anticonvulsants directly. Systemic local anaesthetic-type drugs have been shown to be effective in nerve injury pain but there is little or no evidence to support their use in migraine or cancer-related pain. Topical NSAIDs (for example, gels, creams) are effective in rheumatological conditions with an overall NNT of 3. There are too few studies to determine which is the best agent. Topical NSAIDs have few adverse events; most importantly they are without the major gastrointestinal adverse events found with oral NSAIDs, which might make them an important choice for some patients with peripheral arthritis. (ABSTRACT TRUNCATED)

The effects of a cognitive-behavioral pain management programme on the quality of work and employment status of severely impaired chronic pain patients.

This study examined changes in employment status and quality of work in 109 chronic pain patients who underwent a cognitive-behavioural pain management course; 68% of patients were female, mean age was 45 years, mean pain chronicity 10.7 years, 70% had spinal pain, and mean impairment on the Sickness Impact Profile was 26%. Twenty-six per cent of patients were employed at pre-treatment; the remaining 74% had been unemployed for 4.3 years on average. Measures of work status and quality, mood, pain, self-efficacy and walking performance were taken before admission, and at 1-, 6-, and 12-month follow-ups. Among employed patients quality of work scores improved by 35% from pre- to post-treatment (p < 0.01). Thirty per cent of previously unemployed patients returned to work during the 1-year follow-up, although employment status fluctuated greatly during this period. Non-workers were generally more impaired than workers on most measures, but the same measures did not differentiate between those who successfully returned to work and those who remained unemployed.

Mechanisms of inhibition of mononuclear cell activation by the iron-chelating agent desferrioxamine.

Iron-withholding by the chelating agent desferrioxamine abrogates the proliferative response of human peripheral blood mononuclear cells (PBMC) to phytohaemagglutinin (PHA). The present study investigated whether desferrioxamine operates late in the activation process or, as recently suggested, at an early stage, by inhibiting the appearance of the interleukin-2 (IL-2) receptor. Human PBMC were stimulated with PHA (10 micrograms/ml) and [3H]thymidine ([3H]TdR) incorporation determined after 66 hr of culture. Greater than 90% inhibition was achieved by concentrations of desferrioxamine as low as 5 mumol/l present throughout culture, while IL-2 receptor expression (anti-Tac), analysed by FACS, was maintained at up to 75% of control levels. 300 mumol/l desferrioxamine present throughout culture abrogated [3H]TdR incorporation and additionally suppressed IL-2 receptor to 10-15% of control levels. In contrast, the same high dose of desferrioxamine when added for 2 hr to cells previously cultured for 66 hr produced 80% inhibition of [3H]TdR incorporation but failed to inhibit expression of the IL-2 receptor. Desferrioxamine rapidly achieved equilibrium across the cell membrane (within 60 min) and chelated 59Fe delivered to activated cells by the transferrin endocytic cycle. These results indicate that desferrioxamine can inhibit T-cell activation either early or late in the process by chelating iron and independently of an effect on the IL-2 receptor. In support of a dual effect of the drug is the finding that at 50 mumol/l, desferrioxamine-enhanced expression of the transferrin receptor occurred, an adaptive response made to intracellular iron depletion, while IL-2 receptor expression was inhibited.

Spinal cord stimulation and the relief of chronic pain.

Twenty six patients who had received spinal cord stimulation for chronic pain were evaluated by videotaped structured interviews with staff not directly involved in the patients' care. In addition estimates of pain relief were obtained from clinicians involved in the patients' care and from close relatives and friends. Information about lifestyles and drug usage was also collected and correlated with pain relief. At the time of the interviews half of the patients were receiving 50% or better relief of their pain.

Hypomagnesaemia causing myopathy and hypocalcaemia in an alcoholic.

A well-nourished alcoholic patient developed a subacute myopathy which responded rapidly to correction of severe hypomagnesaemia. The finding of profound hypocalcaemia prompted the measurement of serum magnesium. Magnesium deficiency should be looked for in any alcoholic patient with a myopathy as the prognosis seems better than in many other forms of alcoholic myopathy. Correction of the magnesium deficiency corrects the hypocalcaemia without the need for calcium supplementation.