Rehabilitation for chronic low back pain. Review was of little help in selecting treatment.
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Chronic Disease↗
Biomedical subjects
A C Williams
Publications and source records attributed to A C Williams.
Effect of melting point of chiral terpenes on human stratum corneum uptake.
The effect of melting point of chiral penetration enhancers on their stratum corneum uptake was investigated. The pure enantiomers of a chiral compound often possess different melting points, and therefore dissimilar solubilities, to the racemate because of variations in their crystal structure. Two terpenes, menthol and neomenthol, saturated in propylene glycol/water, were applied to stratum corneum. Racemic menthol melts at approximately 33 degrees C, some 9 degrees C lower than the pure enantiomers, whereas racemic neomenthol melts at 26 degrees C higher than the study temperature, considered as the theoretical melting point of its enantiomers, which are both liquids. Terpene solubility increased with the propylene glycol content of the vehicle. The lower melting forms of both penetration enhancers possessed the highest solubility in every vehicle. Maximum stratum corneum uptake was obtained from formulations containing the lower melting forms of each enhancer in 60% w/w propylene glycol systems (highest concentration used). Compared with menthol, the larger melting point difference between optical forms of neomenthol produced bigger differences in their uptake. Thus melting point depression of menthol and neomenthol, by selection of the appropriate optical form, increased the amount of terpene delivered to the stratum corneum, in agreement with theoretical predictions.
Calorimetry, Differential Scanning↗
Cysteine dioxygenase: regional localisation of protein and mRNA in rat brain.
Cysteine dioxygenase (CDO) converts cysteine to cysteinesulphinic acid and is the rate-limiting step in sulphate production. Most studies have centred upon the hepatic form of the enzyme, but several studies have investigated brain CDO using activity assays and western blotting. The aim of this study was to investigate the expression of CDO in the rat brain using a combination of immunohistochemistry and in situ hybridisation. Affinity-purified anti-R and anti-H CDO antibodies were immunoprecipitated using rat brain homogenate to determine whether the antibodies could remove enzyme activity. Immunohistochemistry and in situ hybridisation were then used to determine the cellular and regional expression of both CDO protein and mRNA. Immunoprecipitation of rat brain homogenate removed up to 98% and 70% (anti-R and anti-H, respectively) of enzyme activity. Nonimmune sheep serum had no effect upon enzyme activity. CDO protein and mRNA was localised solely to the neurones of the brain, including the pyramidal cells of the hippocampus and the Purkinje cells of the cerebellum. Regional localisation varied, with high levels of expression in the hippocampus, the dentate gyrus, the outer cortices of the brain, and the substantia nigra. The relative expression of CDO activity and protein in these regions is most probably a result of the relative abundance of neurones in these regions. CDO expression in the brain may have several possibilities functions, the most likely being the prevention of free radical production by the autoxidation of cysteine and dopamine.
Animals↗
Mechanistic study into the enhanced transdermal permeation of a model beta-blocker, propranolol, by fatty acids: a melting point depression effect.
Transdermal permeation of propranolol through human skin in the presence of fatty acid (lauric, capric) penetration enhancers has been investigated. Thermal analysis showed that binary mixtures of propranolol with either fatty acid were not simple mechanical mixtures of the two components. Propranolol formed 1:1 molar addition compounds with both lauric and capric acids; the addition compound produced from propranolol and lauric acid (m.p. 79 degrees C) also developed eutectic systems with both propranolol (m.p. 54 degrees C) and lauric acid (m.p. 16 degrees C). Similarly, the addition compound made from propranolol and capric acid (m.p. 97 degrees C) formed eutectic systems with propranolol (m.p. 83 degrees C) and capric acid (m.p. 15 degrees C). Infrared analyses indicated that the addition compounds were fatty acid salts of the beta-blocker. The nature of the species permeating through human epidermal membranes from binary mixtures of propranolol with the fatty acids was investigated using a novel attenuated total reflectance Fourier transform infrared method. There was no clear difference in permeation rates of the fatty acids compared with the beta-blocker, suggesting that the permeating species was the intact addition compound. The influence of melting point depression of the beta-blocker fatty acid systems on transdermal permeation was predicted from a mathematical model; predicted and experimentally determined data correlated well thus providing an alternative explanation as to the mode of action of these permeation enhancers.
Administration, Cutaneous↗
IGFBP-3 and apoptosis--a license to kill?
Insulin-like growth factor binding protein (IGFBP)-3, the major carrier of insulin-like growth factors (IGFs) in the circulation, was first isolated and characterised over a decade ago. More recently, IGFBP-3 has been assigned a role as a putative death-promoting factor, a function that appears, under certain circumstances, to be independent of its IGF-binding ability. This review examines the current evidence for a pro-apoptotic function for IGFBP-3 and speculates on its physiological significance.
Animals↗
Outcome assessment in chronic non-cancer pain treatment.
Increased literacy of the pain research community concerning the formal requirements of assessment instruments - reliability, validity and sensitivity to change - means that assessment can now be addressed with reference to underlying dilemmas both about techniques of measurement and its targets. This commentary on outcome assessment is intended to facilitate the choice of measures, from an imperfect field, by raising some of those problems. It deals first with summary measures, and then with the separate domains of pain experience, affect, cognition and coping, behavior and activity, social role interference, biological and fitness measures, and use of health care, addressing in particular the conceptual basis of each.
Chronic Disease↗
Transcriptional down-regulation of the retinoblastoma protein is associated with differentiation and apoptosis in human colorectal epithelial cells.
The aim of this study was to investigate the regulation of Rb protein expression in relation to increased differentiation and induction of apoptosis in colonic epithelial cells. In vivo, Rb protein expression was found to be down-regulated towards the top of the normal colonic crypt, coincident with the region of differentiation and apoptosis, but highly expressed in colonic carcinoma tissue. Using in vitro models to study the regulation of Rb expression in pre-malignant colonic epithelial cells, we have been able to show for the first time that Rb protein expression is transcriptionally down-regulated in differentiated pre-malignant cells (in post-confluent cultures) but not in malignant colorectal epithelial cells. Furthermore, suppression of rb protein function by the HPV-E7 viral oncoprotein increased both spontaneous and DNA damage-induced apoptosis. These results suggest that Rb is able to act as a survival factor in colonic epithelial cells by suppressing apoptosis, and that over-expression of pRb in colorectal tumour cells can cause a loss of sensitivity to apoptotic signalling, resulting in aberrant cell survival and resistance to therapy.
Antibodies, Monoclonal↗
Sexual difficulties of chronic pain patients.
OBJECTIVE: Description of the specific physical and psychological problems associated with sexual activity in patients with chronic pain. DESIGN: Self-completion questionnaire on extent and nature of sexual difficulties related to pain; data on psychological and physical function in respondents; personal and medical data for respondents and nonrespondents. PATIENTS: Three hundred twenty-seven patients with chronic pain in inpatient and outpatient pain programs; 237 (72%) completed the questionnaire. MEASURES: Extent of general and specific sexual problems; anxiety and depression (Hospital Anxiety and Depression Scale [HAD]); pain self-efficacy; pain-related disability (Sickness Impact Profile); drug use. RESULTS: Respondents were younger and had less depressed mood than nonrespondents, but there were no other major differences. Seventy-three percent of respondents had pain-related difficulty with sexual activity; most had several, in various combinations of problems with arousal, position, exacerbating pain, low confidence, performance worries, and relationship problems. All except position difficulties were associated with less frequent sexual activity. There were few differences between men and women, and only weak relations emerged between specific problems and mood and disability. CONCLUSIONS: There is a high prevalence of sexual difficulties in patients with chronic pain attending treatment, nearly double that of a general UK survey. These difficulties are not simply related to mood or disability. The range of problems and patients' expressed preferences for help suggest that multidisciplinary intervention is required.
Adult↗
Preliminary study of chronic pain patients' concerns about cannabinoids as analgesics.
OBJECTIVE: This was a preliminary investigation of patients' beliefs about cannabinoids and the associations between those beliefs, beliefs about medication, and personal and pain variables with regard to patients' willingness to try cannabinoids as analgesics. DESIGN: A self-completion questionnaire was used. SETTING: The investigation took place in an outpatient pain clinic. PATIENTS: Sixty-seven patients with chronic pain were involved. OUTCOME MEASURES: The outcome measures were patients' stated willingness to use cannabinoids and the extent of their agreement or disagreement with statements concerning cannabinoids and medicines in general. RESULTS: Fifty-two percent of patients were doubtful about taking cannabinoids: unwillingness was strongly associated with specific concerns about side effects, addiction, tolerance, and losing control but not with general beliefs about medication or personal or medical variables other than age. CONCLUSIONS: The concerns of patients with chronic pain about taking cannabinoids as analgesics may reduce their utility and efficacy; accurate information is required to counter this effect.
Adult↗
Validation of the WHOQOL-100: pain management improves quality of life for chronic pain patients.
OBJECTIVE: The study aimed to validate a new, multidimensional, multilingual instrument (the WHOQOL-100) for assessing QOL in chronic pain patients. METHODS: Chronic pain patients (N = 106) who agreed to participate in an established pain management program (PMP) were assessed for quality of life (QOL) before and one month after the intervention. The WHOQOL-100 is a generic profile containing 25 facets of QOL organized in 6 domains. It was administered concurrently with the MOS Short Form-36, the Beck Depression Inventory, and measures of pain intensity, duration, disruption and distress. RESULTS: The patients were outpatients and inpatients with a mean age of 44 years and mean pain duration of 8 years. The sample included 70 (66%) women. After the PMP, QOL had significantly improved generally. and in the physical, psychological and independence domains, as well as in 10 facets of QOL including pain and discomfort. Good QOL is consistently associated with low levels of pain severity and pain distress and little pain disruption. Overall internal consistency reliability was good and for most facets and domains but marginal for the pain facet. When compared with the SF-36. the WHOQOL-100 shows good concurrent validity, greater comprehensiveness and very good responsiveness to clinical change. DISCUSSION: The WHOQOL-100 indicates significant improvements to QOL for those entering a PMP and is validated for the clinical assessment of chronic pain patients and for use in multi-national clinical trials, clinical governance and audit.
Adult↗
Outcomes of cleft care in Western Australia: a pilot study.
The purpose of this study was to compare outcomes and delivery of cleft care in Western Australia with the average standard of care in the United Kingdom (UK). This was achieved through a cross-sectional study involving children born with unilateral cleft lip and palate between April 1983 and March 1985 (12 year olds) or between April 1990 and March 1992 (5 year olds). A total of 38 children born with unilateral cleft lip and palate were under the care of the cleft team based at Perth's Princess Margaret Hospital. Dental arch relations, facial skeletal pattern, speech, hearing, success of alveolar bone grafting and dental health were measured. It was found that fewer Princess Margaret Hospital children in both age cohorts had revision surgery and speech therapy compared with the UK average. The facial skeletal pattern, speech, hearing and alveolar bone grafting outcomes from Princess Margaret Hospital were similar to the UK at age 12. Seventeen per cent of the Princess Margaret Hospital 12 year olds had a poor dental arch relationship compared with 39 per cent in the UK. In the 5 year olds, most outcomes in Princess Margaret Hospital patients appeared better than the UK with lower residual treatment needs. While it is difficult to draw firm conclusions because of the small numbers involved, this study indicates standards need to be set and determined for Australia.
Bone Transplantation↗
Renal localisation of rat cysteine dioxygenase.
BACKGROUND/AIMS: Cysteine dioxygenase (CDO, EC 1.13.11.20) catalyses the conversion of cysteine to cysteine sulphinic acid and controls the rate-limiting step of sulphate production. Many neurological and non-neurological diseases are associated with abnormalities in CDO activity, giving rise to reduced availability of sulphate. The importance of the kidney in the sulphation of xenobiotics has long been recognised, but little is known about the renal expression of key enzymes in this pathway. In order to address this, this report demonstrates the expression of CDO in the kidney. METHODS: Two previously characterised antibodies were used to investigate the localisation and expression of CDO using immunohistochemistry, in-situ hybridisation and Western blotting. RESULTS: Renal CDO was shown to exist as a 68-kDa protein, which was unaffected by levels of cysteine and methionine that had been previously shown to induce hepatic CDO. CDO protein expression was present in the proximal convoluted tubules of the cortex and the collecting ducts of both the medulla and papilla. DISCUSSION: These results suggest that renal CDO is immunologically identical to that of the liver. Its expression in the kidney tubules, the major site of sulphation in the kidney, suggests that CDO in the kidney may play a role in both xenobiotic metabolism and sodium and water homeostasis.
Animals↗
Skin delivery of 5-fluorouracil from ultradeformable and standard liposomes in-vitro.
The potential use of ultradeformable and standard liposomes as skin drug delivery systems was investigated in-vitro. An improved experimental design gave a good measure for skin deposition of drug. This avoided the contamination that can occur due to incomplete washing of the donor before direct determination of the amount of drug in the skin. The design used aqueous ethanolic receptor which is believed to diffuse into skin, disrupting deposited liposomes (if any) and thus releasing both bound and free drug. The receptor fluid was refined by testing different concentrations of ethanol. The applied dose was also optimized. Using the improved design and the optimum dose, an ultradeformable formulation was compared with four traditional liposomes for skin delivery of 5-fluorouracil (5-FU). The best receptor was 50% aqueous ethanol and the optimum dose was 20 microL. The ultradeformable formulation was superior to standard liposomes in the skin delivery of 5-FU. Of the traditional liposomes, the non-rigid preparation was the best. However, stabilization of the liposome membrane with cholesterol abolished the benefit of this non-rigid preparation. It was concluded that ultradeformable vesicles are promising agents for skin delivery of drugs.
Aged↗
Skin hydration and possible shunt route penetration in controlled estradiol delivery from ultradeformable and standard liposomes.
Human skin delivery of estradiol from ultradeformable and traditional liposomes was explored, comparing occlusive and open application, with the aim of examining the role of skin hydration. Partially hydrated epidermis was used for open hydration, but fully hydrated membranes were used for occluded studies. In addition, we developed a novel technique to investigate the role of shunt route penetration in skin delivery of liposomal estradiol. This compared delivery through epidermis with that through a stratum corneum (SC)/epidermis sandwich from the same skin with the additional SC forming the top layer of the sandwich. This design was based on the fact that orifices of shunts only occupy 0.1% of skin surface area and thus for SC/epidermis sandwiches there will be a negligible chance for shunts to superimpose. The top SC thus blocks most shunts available on the bottom membrane. If shunts play a major role then the delivery through sandwiches should be much reduced compared with that through epidermis, taking into consideration the expected reduction owing to increased membrane thickness. After open application, both ultradeformable and traditional liposomes improved estradiol skin delivery, with the ultradeformable liposomes being superior. Occlusion reduced the delivering efficiency of both vesicle types, supporting the theory that a hydration gradient provides the driving force. Shunt route penetration was found to play only a very minor role in liposomal delivery. In conclusion, full hydration of skin reduces estradiol delivery from liposomes and the shunt route is not the main pathway for this delivery.
1,2-Dipalmitoylphosphatidylcholine↗
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.
Aged↗
A review of xenobiotic metabolism enzymes in Parkinson's disease and motor neuron disease.
The role of xenobiotic metabolising enzymes (XMEs) in disease aetiology has been under investigation by numerous researchers around the world for the last two decades. The association of a number of defects in both phase I and phase II reactions with Parkinson's disease (PD) and motor neuron disease (MND) have been extensively studied. This review of the work of the group based initially at the University of Birmingham into the functional genomics of XMEs and neurodegenerative diseases has indicated that: 1. Sub-groups of patients with PD and MND can be identified with problems in xenobiotic metabolism by in vivo or in vitro methods. 2. 38-39% of the patients with MND/PD have a defect in the S-oxidation of the mucoactive drug, carbocysteine, by an unknown cytosolic oxidase(s). The odds risk ratio for the association of this defect with these diseases was calculated to be 10.21 for MND and 10.50 for PD. 3. Patients with PD appear to have an altered substrate specificity for monoamine oxidase B substrates in an in vitro platelet assay. 4. Patients with MND have an increased capacity to S-methylate aliphatic sulphydryl compounds in an in vivo challenge as well as an in vitro erythrocyte thiol methyltransferase assay. The results of over a decade of investigations into both PD and MND indicate that these are diseases with mutifactorial origins that encompass both genetic predisposition and environmental insult.
Adult↗
Cleft lip and palate care in the United Kingdom--the Clinical Standards Advisory Group (CSAG) Study. Part 1: background and methodology.
OBJECTIVE: To review the history of cleft care in the United Kingdom and the rationale and methodology of a national study. DESIGN: Descriptive overview to introduce this series of papers. SETTING: Fifty National Health Service cleft teams. PATIENTS/PARTICIPANTS: Two age cohorts, 5-year-olds and 12-year-olds, with nonsyndromic complete unilateral cleft lip and palate and their parents. MAIN OUTCOME MEASURES: Facial development and appearance, quality of bone grafts, speech, oral health and patient/parent satisfaction. CONCLUSIONS: The case for a national assessment of cleft care is made. The methodology of the cross-sectional outcome study is described, together with a survey of training for recently appointed clinicians.
Attitude of Health Personnel↗
Cleft lip and palate care in the United Kingdom--the Clinical Standards Advisory Group (CSAG) Study. Part 2: dentofacial outcomes and patient satisfaction.
OBJECTIVE: To describe facial development and appearance, quality of bone grafts, oral health, and patient/parent satisfaction, with clinical outcome, for children in two age cohorts born with unilateral cleft lip and palate (UCLP) throughout the United Kingdom. DESIGN: Cross-sectional outcome study. SETTING: Fifty National Health Service cleft centers. PARTICIPANTS: Children born with complete UCLP between April 1, 1982, and March 31, 1984, (12-year-olds) and April 1, 1989, and March 31, 1991 (5-year-olds). Data were collected for 239 5-year-olds and 218 12-year-olds. The parents of these children were also interviewed to determine levels of satisfaction with care received. MAIN OUTCOME MEASURES: Skeletal pattern, dental arch relationship, success of alveolar bone grafting, facial appearance, oral health status, and patient/parent satisfaction. RESULTS: Nearly 40% of 5- and 12-year-olds had poor dental arch relations, and 70% of 12-year-olds had midface retrusion. Fifteen percent of 12-year-olds had not received an alveolar bone graft, and only 58% of bone grafts that had been undertaken were successful. Twenty percent of 12-year-olds and 40% of 5-year-olds had untreated dental caries. Less than one-third of subjects had a good facial appearance as judged by a panel of experts. Levels of patient and parent satisfaction were generally high. CONCLUSION: A rigorous evaluation of cleft care in the United Kingdom reveals disappointing outcomes.
Alveoloplasty↗