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Prior research on visual impairments has documented specific challenges that people with low vision face such as reading and mobility. Yet, much less focus has been given to the relationships between seemingly separate challenges such as mobility and social interactions; limiting the potential of services and assistive technologies for people with low vision. To address this gap, we conducted semi-structured interviews with 30 low vision participants and examined the relationships between challenges and coping strategies overarching three facets of life - functional, psychological, and social. We found that challenges in a specific area of life commonly interacted and impacted other facets of life and provide a conceptual map of these relationship. For example, challenges in mobility reduced social interactions, which in turn affected the psychological well-being. Moreover, participants repeatedly described how a seemingly specific functional challenge (i.e., seeing under different lighting conditions) influenced a wide range of activities, from mobility (e.g., seeing obstacles) to social interactions (e.g., seeing faces and interpreting non-verbal cues). Our results highlight the importance of considering the interrelationships between different facets of life for assistive technology development and evaluation.
Subject(s)
Self-Help Devices , Vision, Low , Humans , Vision, Ocular , Social Interaction , Adaptation, PsychologicalABSTRACT
BACKGROUND AND OBJECTIVE: Psychometric tests can provide important information for diagnostics and progression in chronic pain patients. Between 2008 and 2018, the electronic system painDETECT® was used in the outpatient pain clinic of the Hannover Medical School (MHH). The aim of this retrospective study was to evaluate the pain symptomatology data recorded using painDETECT® and the treatment procedures used in the patient cohort examined over a period of 15 months. MATERIAL AND METHODS: A statistical analysis of baseline and follow-up data was performed. The analysis comprised pain-related parameters recorded by use of the painDETECT® system as well as outpatient records. RESULTS: Baseline data of 459 patients (66% women) could be evaluated. The most common clinical pictures were spinal pain, headache, facial pain, and somatoform disorders, mostly with many years of previous treatment. Approximately 40% showed evidence of neuropathic pain components or central sensitization. With a mean pain intensity of VAS 6 (0-10), a predominantly high degree of chronicity was present. Approximately one third showed a high degree of pain-related functional impairment. Slightly more than half showed evidence of clinically relevant depression. Approximately 80% showed clinically relevant sleep disturbances. Follow-up data were available for 145 patients (31.6%). The proportion of patients receiving a nonpharmacological form of treatment increased by 44.1% (physical therapy) and by 24.1% (psychotherapeutic procedures) during the observation period. The use of co-analgesics increased by approximately 30% over the course. CONCLUSION: In the outpatient setting, an extension of treatment can be successful for high-grade chronic pain patients. Close structural networking with the clinics for rehabilitation medicine and for psychosomatics and psychotherapy at the MHH can be a favorable prerequisite for this.
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Blind people face difficulties with independent mobility, impacting employment prospects, social inclusion, and quality of life. Given the advancements in computer vision, with more efficient and effective automated information extraction from visual scenes, it is important to determine what information is worth conveying to blind travelers, especially since people have a limited capacity to receive and process sensory information. We aimed to investigate which objects in a street scene are useful to describe and how those objects should be described. Thirteen cane-using participants, five of whom were early blind, took part in two urban walking experiments. In the first experiment, participants were asked to voice their information needs in the form of questions to the experimenter. In the second experiment, participants were asked to score scene descriptions and navigation instructions, provided by the experimenter, in terms of their usefulness. The descriptions included a variety of objects with various annotations per object. Additionally, we asked participants to rank order the objects and the different descriptions per object in terms of priority and explain why the provided information is or is not useful to them. The results reveal differences between early and late blind participants. Late blind participants requested information more frequently and prioritized information about objects' locations. Our results illustrate how different factors, such as the level of detail, relative position, and what type of information is provided when describing an object, affected the usefulness of scene descriptions. Participants explained how they (indirectly) used information, but they were frequently unable to explain their ratings. The results distinguish between various types of travel information, underscore the importance of featuring these types at multiple levels of abstraction, and highlight gaps in current understanding of travel information needs. Elucidating the information needs of blind travelers is critical for the development of more useful assistive technologies.
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OBJECTIVE: Somatoform disorders and functional somatic syndromes (FSS) with symptoms that are not sufficiently explained by physical or technical examination are among the most challenging underlying causes. Many different somatoform disorders and FSS have overlapping symptoms, often with pain as the most prevalent one, leading to a high burden of disease. The concept of multisomatoform disorder (MSD) has been developed to acknowledge that fact. We analyzed a group of 151 patients and 149 matched controls to identify interactions of genetic and environmental factors with a possible influence on the development of MSD. DESIGN: In a retrospective case-control study, we performed a statistical analysis on 151 patients and 149 matched controls using logistic regression and a Classification and Regression Tree (CART) analysis. RESULTS: The logistic regression analysis of genes and environmental factors demonstrated significant differences in the results of the Trier Inventory of Chronic Stress (TICS) questionnaire, the single nucleotide polymorphism rs1800955 of the dopamine receptor D4 and the single nucleotide polymorphism rs4818 of the enzyme catechol-O-methyltransferase between patients with MSD and healthy controls. The resulting decision tree of the CART analysis determined that the TICS questionnaire was able to differentiate patients and controls most accurately, followed by certain genotypes of the 5-hydroxytryptamine receptor 2A and a single nucleotide polymorphism of the enzyme catechol-O-methyltransferase. CONCLUSIONS: The results of the statistical analysis identified a gene-environmental interaction possibly leading to MSD. The resulting identifiers could be used as a reference to inform diagnostic algorithms to easier identify patients suffering from MSD.
Subject(s)
Catechol O-Methyltransferase , Somatoform Disorders , Case-Control Studies , Catechol O-Methyltransferase/genetics , Genotype , Humans , Pain , Polymorphism, Single Nucleotide/genetics , Retrospective Studies , Somatoform Disorders/diagnosis , Somatoform Disorders/geneticsABSTRACT
BACKGROUND: On 31 December 2016, a total of 1206 physicians participated in the outpatient care of chronic pain patients according to the criteria of a special pain management program (QSV). Because of the largely existing shortage of treatment resources for chronic pain patients, there is a lack of data regarding the evaluation of outpatient pain management by highly specialized pain therapists. METHODS: In a hybrid Delphi procedure, a questionnaire concerning the content, structural and personal assessment of outpatient pain management in Germany was developed. With the help of this instrument, an internet-based cross-sectional survey of 281 QSV pain therapists from four German states (Berlin, Lower Saxony, Saxony, Baden-Württemberg) and of all the heads of university outpatient pain services (nâ¯= 36) in Germany was conducted. RESULTS: The adjusted response rate of the survey was 35.9%. The response rate of the heads of university outpatient pain services was 66.7%. In 91% of the respondents the proportion of chronic pain patients in the medical practices was more than 70%. Whereas 67.3% were satisfied with the situation in their medical practice, 63.4% were dissatisfied with the current organizational structure of the pain management in Germany. They expressed their dissatisfaction especially in terms of budgeting regulations (69.3%), the cooperation with psychotherapists (69.3%) and interdisciplinary networking (50.5%). The 1year specialist training in pain management (87.1%) and the completion of a psychosomatic basic care course (90.1%) were assessed as a good preparation for the later profession. A multitude of free comments indicated that the pain specialist training is too short and insufficient. Most of the respondents considered the establishment of a specialist board certification for pain management more suitable from the perspective of physicians (61.4%) and the patients (54.5%). Of the heads of university outpatient pain services 70.8% expressed the wish for autonomous structures with separate budgets and 75.0% indicated that under the current conditions their outpatient pain services are not working profitably. Only 39.7% of the QSV pain therapists provided fellowship training for physicians and 57.6% were planning to retire during the next 10 years. CONCLUSION: Highly specialized pain therapists are dissatisfied because of the lack of independence of the organizational structure of pain management care and the insufficient interdisciplinary network in outpatient pain management. A possible solution for a better pain management care and the recruitment problems may be the establishment of a board certification for pain management.
Subject(s)
Outpatients , Pain Management , Berlin , Cross-Sectional Studies , Germany , Humans , Internet , SpecializationABSTRACT
BACKGROUND: This study aims to evaluate the feasibility and efficacy of a complex health intervention, based on the combination of conventional Western medicine and traditional Chinese medicine (TCM), in an outpatient department of a university hospital for patients with frequent episodic or chronic tension-type headaches. METHODS/DESIGN: This is a prospective randomized controlled pilot study with four balanced treatment arms (usual care, acupuncture, training, and training plus acupuncture). Each arm will have 24 patients. After the initial screening examination and randomization, a 6-week treatment period follows, with treatment frequencies decreasing at 2-week intervals. After completion of the intervention, two follow-up evaluations will be performed 3 and 6 months after the start of treatment. At predefined times, the various outcomes (pain intensity, health-related quality of life, pain duration, autonomic regulation, and heart rate variability) as well as the participants' acceptance of the complex treatment will be evaluated with valid assessment instruments (Migraine Disability Assessment, PHQ-D, GAD-7, and SF-12) and a headache diary. The acupuncture treatment will be based on the rules of TCM, comprising a standardized combination of acupuncture points and additional points selected according to individual pain localization. The training therapy comprises a combination of strength training, endurance training, and training to improve flexibility and coordination. Besides descriptive analyses of the samples, their comparability will be assessed using an analysis of variance (ANOVA) or chi-squared tests. Analyses will be performed on an intention-to-treat basis. Potential interaction effects will be calculated using a repeated-measures ANOVA to test the primary and secondary hypotheses. In supplementary analyses, the proportion of treatment responders (those with a 50% reduction in the frequency of pain episodes) will be determined for each treatment arm. DISCUSSION: This trial may provide evidence for the additive effects of acupuncture and medical training therapy as a combination treatment and may scientifically support the implementation of this complex health intervention. TRIAL REGISTRATION: Registered on 11 Feburary 2019. German Clinical Trials Register, DRKS00016723.
Subject(s)
Acupuncture Therapy , Endurance Training , Randomized Controlled Trials as Topic , Resistance Training , Tension-Type Headache/therapy , Acupuncture Therapy/adverse effects , Adult , Combined Modality Therapy , Humans , Medicine, Chinese Traditional , Outcome Assessment, Health Care , Pilot Projects , Prospective Studies , Quality of Life , Tension-Type Headache/psychologyABSTRACT
OBJECTIVES: Previously, we found in cultures of primary neurons and in animals that sensitized primary neurons can be desensitized by treatment with e.g. beta-adrenergic receptor agonists. We now tested whether also in human sensitization such as UVB-radiation induced sunburn-like hyperalgesia can be reduced by intradermal injection of the beta-adrenergic receptor agonist terbutaline. METHODS: In our prospective randomized study, 17 participants received an individual UVB dose to cause a defined local sunburn-like erythema at four locations, two on each forearm. Twenty-four hours later, the sensitized four areas were injected intradermally with terbutaline pH 4.3, terbutaline pH 7.0, saline pH 4.3 or saline pH 7.0, respectively. Pain thresholds were examined before and after induction of UVB-sensitization, and 15, 30 and 60 min after injection of the respective solution. Mechanical pain thresholds of the skin and of deeper tissues were determined by pinprick and pressure algometer measurements, respectively. RESULTS: UVB-irradiation decreased mechanical pain thresholds for pinprick and pressure algometer measurements demonstrating a successful sunburn-like sensitization. Intradermal injection of terbutaline pH 7.0 into the sensitized skin reduced the sensitization for all measured timepoints as determined by pinprick measurements. Pinprick measurements of sensitization were not reduced by injection of terbutaline pH 4.3, saline solution pH 7.0 or saline solution pH 4.3. Also, sensitization of deeper tissue nociceptors were not altered by any of the injections as measured with the pressure algometer. CONCLUSIONS: Similar to our cellular observations, also in humans beta-adrenergic agonists such as terbutaline can reduce the sensitization of primary neurons in the skin. SIGNIFICANCE: We previously showed in model systems that beta-adrenergic stimulation can not only sensitize but also desensitize nociceptors. Our study shows that also in humans beta-adrenergic agonists desensitize if injected into UVB-sensitized skin. This indicates an analgesic activity of adrenergic agonists in addition to their vasoconstrictory function.
Subject(s)
Adrenergic beta-Agonists/pharmacology , Central Nervous System Sensitization/drug effects , Hyperalgesia/etiology , Pain Threshold/drug effects , Sunburn/complications , Terbutaline/pharmacology , Ultraviolet Rays , Adult , Analgesics , Animals , Humans , Injections, Intradermal , Male , Nociceptors/drug effects , Prospective Studies , Skin , Young AdultABSTRACT
INTRODUCTION: Complex regional pain syndrome (CRPS) is a complication following trauma or surgery and may be difficult to diagnose since biomarkers are lacking. Using protein array technology, we found antibodies binding to p29ING4, which we further characterized using ELISA. METHODS: Thirty-six sera of early-stage type 1 CRPS, 66 sera of rheumatoid arthritis (RA), 53 sera of axial spondyloarthritis (axSpA), 29 sera of psoriatic arthritis (PsA), 22 sera of patients after radial fractures (trauma control), and 100 sera of blood donors (BD) were analyzed for anti-p29ING4. We established ELISAs with 7 different antigens and using different secondary antibodies binding to IgG, IgG1, IgG2, IgG3, IgG4, IgA, and IgM, and 2 different tests to detect immune complexes (IC) of p29ING4 and IgG or IgG1. RESULTS: The highest likelihood ratios versus CRPS and trauma control were observed considering the A1-23 (sensitivity 19%, specificity 100%, LR > 19) using IgG as a secondary antibody, the A120-165 (sensitivity 17%, specificity 100%, LR = 17) using IgG as a secondary antibody and the A120-165 (sensitivity 31%, specificity 95%, LR = 6.2) using IgA as a secondary antibody. IC of p29ING4 and IgG were present in 11/36 (31%) CRPS sera, 17/64 (27%) RA sera, 13/53 (25%) SpA sera, 5/29 (17%) PsA sera, 1/22 (5%) trauma control sera, and 4/100 (4%) sera of BD. IC of p29ING4 and IgG1 were present in 14/36 (39%) CRPS sera, 19/64 (30%) RA sera, 13/53 (25%) SpA, 1/29 (3%) PsA, 2/22 (9%) trauma control, and 4/100 (4%) of the BD sera. CONCLUSION: Due to the lack of other biomarkers of type 1 CRPS, P29ING4 autoantibodies could be helpful in its diagnostic work-up.
Subject(s)
Arthritis, Rheumatoid/immunology , Autoantibodies/immunology , Cell Cycle Proteins/immunology , Complex Regional Pain Syndromes/immunology , Homeodomain Proteins/immunology , Pain/immunology , Tumor Suppressor Proteins/immunology , Adult , Aged , Arthritis, Psoriatic/immunology , Female , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Male , Middle Aged , Young AdultABSTRACT
BACKGROUND: The subjective state of health with respect to pain and psyche was surveyed utilizing validated pain questionnaires in patients undergoing special pain therapy and represents the basis for targeted treatment measures. OBJECTIVE: The purpose of this study was to investigate the possible distortion of answers due to social desirability of responses in chronic pain patients. MATERIAL AND METHODS: During two survey periods assessing patient satisfaction using both anonymized and personalized questionnaires, the effects arising from socially desirable response patterns were analyzed. The sample consisted of chronic pain patients being treated in an inpatient therapy setting. RESULTS: In both periods of observation no significant impact on the response behavior of chronic pain patients was found in personalized or anonymized questionnaires. CONCLUSION: The results of the study suggest that the responses of chronic pain patients with respect to their subjective state of health are not influenced by social desirability. Thus, scoring systems such as the German pain questionnaire will not be influenced by social desirability in chronic pain patients and can therefore be used as a part of diagnostics and therapy planning.
Subject(s)
Chronic Pain , Social Desirability , Humans , Surveys and QuestionnairesABSTRACT
The endocannabinoid system (ECS) controls a large number of vital functions. Suboptimal tone of the ECS in certain regions of the nervous system may be associated with disorders that are also associated with pain. Pain and inflammation processes can be modulated by the exogenous supply of cannabinoids. Low-to-moderate pain-relieving effects and in individual cases large pain-relieving effects were observed in randomized, controlled studies of various types of chronic pain. People with chronic neuropathic pain and stress symptoms seem to particularly benefit. The therapeutic range of cannabinoids is small; often small doses are sufficient for clinically significant effects. The "Cannabis-als-Medizin-Gesetz" (cannabis as medicine law) allows the prescription of cannabis preparations under certain conditions. Available data indicate good long-term efficacy and tolerability. However, there is little systematic long-term experience from clinical studies.
Subject(s)
Cannabinoids , Chronic Pain , Neuralgia , Pain Management , Analgesics , Cannabinoids/therapeutic use , Humans , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVE: To evaluate the effectiveness of intraoperative and postoperative intermittent pneumatic compression (IPC) as a method used to decrease the incidence of deep venous thrombosis (DVT), in comparison to the standard use of graduated compression stockings, low-molecular weight heparin (LMWH) and physiotherapy during the hospital stay. All patients in this study underwent intracranial surgery for glioblastoma multiforme (GBM) using intraoperative magnetic resonance imaging (MRI) guidance. PATIENTS AND METHODS: We performed a single center retrospective study of a cohort of 153 patients who underwent surgery for GBM aided by intraoperative MRI from October of 2009 to January of 2015 at the International Neuroscience Institute (INI), Hannover, Germany. Out of all patients, 75 in comparison to 78 were operated with and without the additional use of IPC, respectively. Both groups received graduated compression stockings, LMWH and physiotherapy postoperatively as a basic thromboprophylaxis. Postoperatively the patients were screened for DVT by Doppler ultrasonography of the limbs and pulmonary embolism (PE) by CT-scan of the chest. RESULTS: DVTs were found in 6 patients with IPC and in 3 patients without IPC. The incidence of developing DVTs was therefore not significantly increased with the application of IPC from 3.9% to 8% (P-value: 0.33). No statistically significant differences were found in the probability of occurrence of pulmonary embolism (PE) with a reduction from 2.6% to 1.3% (P-value: 0.59). CONCLUSION: Our results demonstrate, that the surgical intervention and the subsequent patient immobilization, as well as the thromboprophylactic techniques used have a relatively low influence on the occurrence of thromboembolic complications than we expected. Our findings might be attributed to the overall low number of these complications in a glioblastoma multiforme patient population expected to be at a high risk for coagulopathy. In other words, in order to produce statistically significant results, we would need to increase the patient cohort. By doing so we may better detect a positive therapeutic effect. Alternatively, because of the multitude of possible complex risk-factors leading to coagulopathy in a glioblastoma patient population it might be the case that IPC has little or no effect and that there is a different underlying mechanism responsible for the observed coagulopathy.
Subject(s)
Glioblastoma/drug therapy , Intermittent Pneumatic Compression Devices , Postoperative Complications/prevention & control , Pulmonary Embolism/surgery , Venous Thrombosis/surgery , Adult , Aged , Female , Glioblastoma/complications , Glioblastoma/diagnostic imaging , Heparin, Low-Molecular-Weight/pharmacology , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Retrospective Studies , Risk FactorsABSTRACT
Throughout Europe, chronic pain syndromes occur with a point prevalence of about 20%, with somatic, psychological, and social factors playing a significant role for their development. Therefore, a careful evaluation of the interaction of these factors is the decisive step for a successful therapy. New insights into pathophysiological processes associated with chronic pain have led to an increasing differentiation of drug and non-drug strategies. These strategies take individual factors into account and aim on influencing the neural network for chronic pain. The drugs used are chosen on the basis of pathophysiological findings and specific drug effects. Adjunctive agents are often used in the management of chronic pain. Knowledge of anti-allodynic and anti-hyperalgesic drugs such as antidepressants and anticonvulsants increases continuously and is therefore presented in more detail in the present study.
Subject(s)
Analgesics/therapeutic use , Chronic Pain/drug therapy , Hyperalgesia/drug therapy , Anticonvulsants/therapeutic use , Antidepressive Agents/therapeutic use , Chronic Pain/diagnosis , Chronic Pain/epidemiology , Europe/epidemiology , HumansABSTRACT
BACKGROUND: Acupuncture is a promising treatment approach in patients with chronic low back pain (cLBP) but little is known about the quality of acupuncture in randomized controlled trials (RCT) of acupuncture cLBP. - OBJECTIVE: To determine how international experts (IES) rate the quality of acupuncture in RCTs of cLBP; independent international validation of the Low Back Pain Acupuncture Score (LBPAS). METHODOLOGY: Fifteen experts from 9 different countries outside China were surveyed (IES). They were asked to read anonymized excerpts of 24 RCTs of cLBP and answer a three-item questionnaire on how the method of acupuncture conformed to 1) Chinese textbook standards, 2) the expert?s personally preferred style, and 3) how acupuncture is performed in the expert?s country. Likert scale rating, calculation of the mode for each answer, and Spearman?s rank correlation coefficient between all three answers and the LBPAS were calculated. RESULTS: On comparison with Chinese textbook standards (question 1), 6 RCTs received a good rating, 8 trials a fair and 10 trials a poor or very poor rating. 5 of the 6 trials rated good, received at least a good rating also in question 2 or 3. We found a high correlation of 0.85 (p<0.0001) between the IES and LBPAS ratings for question 1 and question 2, and a correlation of 0.66 (p<0.0001) for question 3. CONCLUSION: The international expert survey (IES) revealed that only 6 out of 24 (25%) RCTs of acupuncture for cLBP were rated "good" in respect to Chinese textbook acupuncture standards. There were only small differences in how the acupuncture quality was rated in comparison to Chinese textbook acupuncture, personally preferred and local styles of acupuncture. The rating showed a high correlation with the Low Back Pain Acupuncture Score LBPAS.
Subject(s)
Acupuncture , Low Back Pain/therapy , Randomized Controlled Trials as Topic , Humans , Surveys and QuestionnairesABSTRACT
BACKGROUND: The dimensions of orally administered pharmacological placebos in routine clinical practice and the attitude of the clinical staff towards placebos are widely unknown. The aim of this report was to examine the frequency, indications and the intentions of placebo use at the Medical University of Hannover (MHH). METHODS: This study was performed as an anonymous cross-sectional written survey at the MHH. Quantitative data on placebo requests registered by the dispensary were obtained in advance. RESULTS: A total of 74% of respondents reported using placebos in clinical practice, including 53% of physicians and 88% of the nursing staff. Pain (76%) and insomnia (59%) were the most frequently reported reasons for administering placebos. Placebos were considered to be highly effective by 28.5% of physicians and 63.8% of the nursing staff. CONCLUSION: The effective use of pharmacological placebos appears to be an established component of the therapeutic options of a tertiary referral center. The placebo effect seems to contain remarkable potential. While the use of pharmacological placebos is ethically problematic within the clinical context, the improvement of caregiver-patient interactions and the utilization of positive suggestion could serve as an ideal adjunct to active therapy regimes.
Subject(s)
Academic Medical Centers , Attitude of Health Personnel , Depression/drug therapy , Dyspepsia/drug therapy , Pain/drug therapy , Placebos/therapeutic use , Sleep Initiation and Maintenance Disorders/drug therapy , Adult , Cross-Sectional Studies , Data Collection , Ethics, Medical , Ethics, Nursing , Female , Germany , Humans , Male , Medical Staff, Hospital/ethics , Middle Aged , Nursing Staff, Hospital/ethics , Referral and Consultation , Treatment Outcome , Young AdultABSTRACT
We identified a unique family with autosomal dominant heart disease variably expressed as restrictive cardiomyopathy (RCM), hypertrophic cardiomyopathy (HCM), and dilated cardiomyopathy (DCM), and sought to identify the molecular defect that triggered divergent remodeling pathways. Polymorphic DNA markers for nine sarcomeric genes for DCM and/or HCM were tested for segregation with disease. Linkage to eight genes was excluded, but a cardiac troponin T (TNNT2) marker cosegregated with the disease phenotype. Sequencing of TNNT2 identified a heterozygous missense mutation resulting in an I79N substitution, inherited by all nine affected family members but by none of the six unaffected relatives. Mutation carriers were diagnosed with RCM (n = 2), non-obstructive HCM (n = 3), DCM (n = 2), mixed cardiomyopathy (n = 1), and mild concentric left ventricular hypertrophy (n = 1). Endomyocardial biopsy in the proband revealed non-specific fibrosis, myocyte hypertrophy, and no myofibrillar disarray. Restrictive Doppler filling patterns, atrial enlargement, and pulmonary hypertension were observed among family members regardless of cardiomyopathy subtype. Mutation of a sarcomeric protein gene can cause RCM, HCM, and DCM within the same family, underscoring the necessity of comprehensive morphological and physiological cardiac assessment in familial cardiomyopathy screening.
Subject(s)
Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Hypertrophic, Familial/genetics , Cardiomyopathy, Restrictive/genetics , Mutation , Troponin T/genetics , Adult , Aged , Cardiomyopathy, Dilated/physiopathology , Cardiomyopathy, Restrictive/physiopathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , PedigreeABSTRACT
BACKGROUND AND PURPOSE: Voltage-operated sodium channels constitute major target sites for local anaesthetic-like action. The clinical use of local anaesthetics is still limited by severe side effects, in particular, arrhythmias and convulsions. These side effects render the search for new local anaesthetics a matter of high interest. EXPERIMENTAL APPROACH: We have investigated the effects of three halogenated structural analogues of propofol on voltage-operated human skeletal muscle sodium channels (Na(V)1.4) and the effect of one compound (4-chloropropofol) on neuronal sodium channels (Na(V)1.2) heterologously expressed in human embryonic kidney cell line 293. KEY RESULTS: 4-Iodo-, 4-bromo- and 4-chloropropofol reversibly suppressed depolarization-induced whole-cell sodium inward currents with high potency. The IC(50) for block of resting channels at -150 mV was 2.3, 3.9 and 11.3 microM in Na(V)1.4, respectively, and 29.2 microM for 4-chloropropofol in Na(V)1.2. Membrane depolarization inducing inactivation strongly increased the blocking potency of all compounds. Estimated affinities for the fast-inactivated channel state were 81 nM, 312 nM and 227 nM for 4-iodopropofol, 4-bromopropofol and 4-chloropropofol in Na(V)1.4, and 450 nM for 4-chloropropofol in Na(V)1.2. Recovery from fast inactivation was prolonged in the presence of drug leading to an accumulation of block during repetitive stimulation at high frequencies (100 Hz). CONCLUSIONS AND IMPLICATIONS: Halogenated propofol analogues constitute a novel class of sodium channel-blocking drugs possessing almost 100-fold higher potency compared with the local anaesthetic and anti-arrhythmic drug lidocaine. Preferential drug binding to inactivated channel states suggests that halogenated propofol analogues might be especially effective in suppressing ectopic discharges in a variety of pathological conditions.
Subject(s)
Membrane Potentials/drug effects , Muscle, Skeletal/drug effects , Neurons/drug effects , Propofol/pharmacology , Sodium Channel Blockers/pharmacology , Sodium Channels/metabolism , Animals , Cell Line , Halogens/chemistry , Humans , Muscle, Skeletal/metabolism , Propofol/analogs & derivatives , Propofol/chemistry , Rats , Sodium Channel Blockers/chemistryABSTRACT
Opinions of acupuncture experts should always be sought in any lawsuit or claim for compensation involving sequelae of acupuncture treatment. Overall,--in the hands of experienced acupuncturists--acupuncture is very safe but not without minor adverse events. However, serious adverse events are extremely rare, especially the risk of a serious vascular lesion. In contrast, inflammatory bowel disease is an independent and disease specific risk factor for thromboembolism, especially if the disease is highly active.
Subject(s)
Acupuncture Therapy/adverse effects , Amputation, Surgical , Elbow/surgery , Risk Assessment/methods , Thromboembolism/etiology , Thromboembolism/surgery , Female , Germany , Humans , Incidence , Middle Aged , Risk FactorsABSTRACT
Accidental intrarterial injections are not uncommon in medical treatments. This is also true for uncontrolled injections by drug-addicts. Since 2002 a number of 600 heavy opiate addicts in Germany are substituted in a country-wide study with pure diacetylmorphine (Heroine). We report the course and outcome of three cases of accidental intraarterial injections of pure diacetylmorphine under controlled conditions. After initial symptoms of vasospasms, all cases were without symptoms within one hour and no obvious loss of tissue was observed. After discussing the literature about medical literature and treatment options in intraarterial injections it is concluded, that the cause of major complications after intraarterial injections may not be the pure diacetylmorphine but additional substances in impure "street-heroin" samples.
Subject(s)
Heroin Dependence/complications , Heroin/administration & dosage , Heroin/poisoning , Adult , HIV Infections/complications , Hepatitis C/complications , Humans , Injections, Intra-Arterial , MaleABSTRACT
For about 5,000 years, cannabis has been used as a therapeutic agent. There has been growing interest in the medical use of cannabinoids. This is based on the discovery that cannabinoids act with specific receptors (CB1 and CB2). CB1 receptors are located in specific brain areas (e.g. cerebellum, basal ganglia, and hippocampus) and CB2 receptors on cells of the immune system. Endogenous ligands of the cannabinoid receptors were also discovered (e.g. anandamids). Many physiologic processes are modulated by the two subtypes of cannabinoid receptor: motor functions, memory, appetite, and pain. These innovative neurobiologic/pharmacologic findings could possibly lead to the use of synthetic and natural cannabinoids as therapeutic agents in various areas. Until now, cannabinoids were used as antiemetic agents in chemotherapy-induced emesis and in patients with HIV-wasting syndrome. Evidence suggests that cannabinoids may prove useful in some other diseases, e.g. movement disorders such as Gilles de la Tourette's syndrome, multiple sclerosis, and pain. These new findings also explain the acute adverse effects following cannabis use.