Pain-related psychological issues in hand therapy

Study Design

Literature review.

Comparison of standard PCR and the LightCycler technique to determine the thrombophilic mutations: an efficiency and cost study.

For several years it has been possible to routinely detect numerous mutations in the human genome by different methods. The most common technique is a standard PCR, but real time fluorescence PCR is increasingly being used. The purpose of this paper is to compare these two different techniques from the point of view of reliability, time consumption, and cost. More than 600 DNA samples of prevalence studies and from cancer patients were used to determine mutations in the genes of coagulation factor V Leiden, prothrombin, and methylenetetrahydrofolate reductase using standard PCR. A subset of 132 samples from the same pool was also tested by LightCycler PCR for the same coagulation gene mutations. Originally LightCycler techniques were applied for quantitative PCR by real time fluorescence measuring. Adding a melting curve analysis allows mutation detection. The results were perfectly concordant. The cost for the reagents is nearly the same for both methods but the time consumption for standard PCR is much higher than for the LightCycler method, resulting in higher laboratory personnel costs.     

Update on age-appropriate preventive measures and screening for Canadian primary care providers

ObjectiveTo summarize the best available age-appropriate, evidence-based guidelines for prevention and screening in Canadian adults.ConclusionWhether primary care providers use a dedicated preventive health visit or opportunistic preventive counseling and screening in their patient encounters, this summary of evidence-based recommendations can help maximize efficiency and prevent important omissions and unnecessary screening.Useful charting tools for preventive care have been published in the past^1–4 but not all such resources are regularly updated. There is a lack of recent comprehensive guides to facilitate delivery and charting of appropriate evidence-based primary care. Recommendations for screening come from various organizations and are constantly changing, rendering health promotion and disease prevention a daunting task. Currently, navigating the plethora of available information in a search of prevention guidelines is overwhelming. There is a need for regular updates through systematic literature reviews. Piecing together these guidelines into a single summary table for practical use in a busy clinical setting simplifies access to information and allows practitioners to provide preventive care in an efficient, evidence-based manner.Chronic disease management is an economic burden to the health care system.⁵ Savings through prevention have been explored by several sources, with emphasis on quality of life and increase in years lived.^6,7 The Choosing Wisely movement is publicizing the disadvantages of causing harm with tests that are not evidence based.⁸ By facilitating opportunities for prevention through easy access to best-practice guidelines, the incidence of chronic disease might decrease, resulting in improved patient-centred care and savings to the health care system.We performed a review of the literature and created a concise table summarizing the findings, as well as charting tools to aid in documentation. After reading this article, providers will be able to list the evidence-based recommendations for preventive maneuvers in healthy adults of different ages and sexes.     

Effect of Sch1000 in allergen-induced asthma.

Carefully controlled allergen inhalation tests were carried out in twelve subjects to provoke early asthmatic responses with a mean maximum FEV1 fall of 30.7 +/- 5.2% (mean +/- s.d.). Four subjects had additional late asthmatic responses with a maximum mean FEV1 fall of 21.0 +/- 5.9%. The tests were repeated at intervals of 7 days in an identical way, following inhalation of Sch1000 (80 microgram) and placebo, each given 45 min before the onset of the early asthmatic response. This dose of Sch1000 produced a marked and uniform inhibition of methacholine-induced bronchoconstriction in the same subjects. The allergen-induced responses were reproducible in eleven out of the twelve subjects; the coefficient of variation for the decrease in FEV1 in the early responses being +/- 7% and in the late response +/- 43%. Sch1000 produced a slight and variable inhibition of early asthmatic responses (P less than 0.02) and no inhibition of late asthmatic responses. We examined the relationship between the degree of inhibition of the early asthmatic response by Sch1000 and : (a) the degree of inhibition produced by Sch1000 on histamine- and methacholine-induced bronchoconstriction; (b) the level of non-specific bronchial reactivity measured by inhaled histamine and methacholine; and (c) the degree of bronchodilatation produced by Sch1000. No relationship was found.     

Cell-based protein vaccines for influenza

An overview of influenza vaccines in development is provided, with an emphasis on new cell-based protein vaccine candidates. The current licensed vaccine is a cost-effective means to reduce the impact of influenza with a known mechanism of action. Most vaccine companies are focusing on the production of whole influenza viruses in various cell lines to replace egg-based manufacturing technology. Only a limited number of targets have been identified for the development of cell-based protein influenza vaccines. They include hemagglutinin, neuraminidase, M2 and nucleocapsid protein. These protein-based vaccine candidates are discussed, along with their progress in clinical development and the advantages and disadvantages of each vaccine approach.     

A proteolytic nanobiocatalyst with built-in disulphide reducing properties

We report a method to equip proteolytic nanobiocatalysts with intrinsic disulphide bond reducing properties. After immobilisation onto silica particles, selected protease enzymes are partially shielded in a nanometre-thick mercaptosilica layer acting not only as a protective system but also as a substrate reducing agent. The biocatalysts produced efficiently perform simultaneous disulphide bond reduction and protein digestion. Besides a significant simplification of the proteolysis process, this strategy allows for a drastic increase of the enzyme stability.

Proteolytic nanobiocatalysts are equipped with intrinsic disulphide bond reducing properties.     

Management of chronic neuropathic pain with methadone: a review of 13 cases

The synthetic opioid methadone has generated much interest in recent years among clinicians involved in the management of intractable chronic cancer pain. Its use as an analgesic is starting to extend to the treatment of noncancer pain, particularly neuropathic pain. Unfortunately, the evidence for its use in the management of neuropathic pain is limited to a few case studies. We examined retrospectively during a 12-month study period the clinical response of all 13 patients at our pain clinic who were prescribed methadone in an attempt to control neuropathic pain resistant to conventional analgesics. A questionnaire was also administered to the 9 patients who continued to take methadone at 12 months posttreatment. A total of 4 patients (31%) discontinued it by the end of the 12-month study period. Patients discontinued methadone due to the absence of pain relief and due to various intractable, undesirable side effects. Somnolence was the most common adverse effect reported, followed by nausea, constipation, and vomiting. All patients took coanalgesics (eg, amitriptyline, gabapentin) or other analgesics (eg, morphine, nonsteroidal anti-inflammatory drugs) during methadone treatment to control pain. The 9 patients who continued to take methadone at 12 months reported experiencing on average 43% pain relief (range 0-80%), 47% improvement in quality of life (range 0-100%), and 30% improvement in quality of sleep (range 0-60%). Methadone was effective at relieving pain and ameliorating quality of life and sleep in 62% of patients. These findings suggest that methadone can offer an acceptable success rate for the treatment of neuropathic pain. Prospective randomized, placebo-controlled studies are now needed to examine more rigorously the benefits of methadone for this type of pain.     

Ultimate journey of the terminally ill: Ways and pathways of hope

ObjectiveTo better understand the role of hope among terminally ill cancer patients.DesignQualitative analysis.SettingA tertiary specialized cancer centre in Canada.ParticipantsCancer patients in palliative care with an estimated remaining life expectancy of 12 months or less (N = 12) and their loved ones (N = 12) and treating physicians (N = 12).MethodsEach patient underwent up to 3 interviews and identified a loved one who participated in 1 interview. Treating physicians were also interviewed. All interviews were fully transcribed and analyzed by at least 2 investigators. Interviews were collected until saturation occurred.ConclusionApproaches aimed at sustaining hope need to reflect that patients’ reactions might fluctuate between despair and a form of acceptance that leads to a certain serenity. Clinicians need to maintain some degree of hope while remaining as realistic as possible. The findings also raise questions about how hope influences patients’ perceptions and acceptance of their treatments.     

Collagen‐mediated hemostasis

Collagens mediate essential hemostasis by maintaining the integrity and stability of the vascular wall. Imbalanced turnover of collagens by uncontrolled formation and/or degradation may result in pathologic conditions such as fibrosis. Thickening of the vessel wall because of accumulation of collagens may lead to arterial occlusion or thrombosis. Thinning of the wall because of collagen degradation or deficiency may lead to rupture of the vessel wall or aneurysm. Preventing excessive hemorrhage or thrombosis relies on collagen‐mediated actions. Von Willebrand factor, integrins and glycoprotein VI, as well as clotting factors, can bind collagen to restore normal hemostasis after trauma. This review outlines the essential roles of collagens in mediating hemostasis, with a focus on collagens types I, III, IV, VI, XV, and XVIII.     

Unconjugated bile salts shuttle through hepatocyte peroxisomes for taurine conjugation

Bile acid-CoA:amino acid N-acyltransferase (BAAT) conjugates bile salts to glycine or taurine, which is the final step in bile salt biosynthesis. In addition, BAAT is required for reconjugation of bile salts in the enterohepatic circulation. Recently, we showed that BAAT is a peroxisomal protein, implying shuttling of bile salts through peroxisomes for reconjugation. However, the subcellular location of BAAT remains a topic of debate. The aim of this study was to obtain direct proof for reconjugation of bile salts in peroxisomes. Primary rat hepatocytes were incubated with deuterium-labeled cholic acid (D(4)CA). Over time, media and cells were collected and the levels of D(4)CA, D(4)-tauro-CA (D(4)TCA), and D(4)-glyco-CA (D(4)GCA) were quantified by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Subcellular accumulation of D(4)-labeled bile salts was analyzed by digitonin permeabilization assays and subcellular fractionation experiments. Within 24 hours, cultured rat hepatocytes efficiently (>90%) converted and secreted 100 μM D(4)CA to D(4)TCA and D(4)GCA. The relative amounts of D(4)TCA and D(4)GCA produced were dependent on the presence of glycine or taurine in the medium. Treatment of D(4)CA-exposed hepatocytes with 30-150 μg/mL digitonin led to the complete release of D(4)CA, D(4)GCA, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) (cytosolic marker). Full release of D(4)TCA, catalase, and BAAT was only observed at 500 μg/mL digitonin, indicating the presence of D(4)TCA in membrane-enclosed organelles. D(4)TCA was detected in fractions of purified peroxisomes, which did not contain D(4)CA and D(4)GCA. Conclusion: We established a novel assay to study conjugation and intra- and transcellular transport of bile salts. Using this assay, we show that cholic acid shuttles through peroxisomes for taurine-conjugation.