Die offene Therapie des femoroazetabulären Impingements [Open therapy of femoroacetabular impingement]

Elimination of an intraarticular femoroacetabular impingement conflict. Creation of a pain-free, normal range of motion of the hip.

Factors determining the success of radiofrequency denervation in lumbar facet joint pain: a prospective study

Background and aims Radiofrequency denervation (RF) of the lumbar facet joints has been shown to be effective in well-selected patients. However, long-term success varies between studies. We evaluated the influence of selected psychosocial and constitutional factors on the outcome of RF, expressed as the duration of pain relief. Methods This prospective observational study included 44 patients who received RF denervations at the University Hospital of Berne. Success was defined as at least 50% pain reduction 7–21 days, 6 months and 1 year after RF therapy. The Cox-regression analysis was performed to evaluate the influence of the following factors on the duration of success: age, sex, depression, work inability and previous surgery. Results Complete follow-up was available for 41 patients. The success rate 7–21 days after the denervation was 76%. It decreased to 32% at 6 months and to 22% at 1 year. The median success duration was 17 weeks (95% CI 10–26). The Cox-regression analysis showed a significant shorter duration of success for patients with depression (hazard ratio [HR] 2.97, 95% CI 1.32–6.65), previous surgery (HR 2.39, 95% CI 1.10–5.21) and number of treated joints (HR 1.95 for each increase in the number of joints, 95% CI 1.14–3.33). In bivariate analyses, only depression was kept to be significant. Conclusions Depression seems to be related with a short duration of success. Based on these findings, a comprehensive study is warranted to evaluate whether psychosocial factors have to be considered when recruiting patients for radiofrequency denervation.

[Functional abdominal pain]

Functional abdominal pain is an inhomogeneous group of disorders concerning aetiology and clinical presentation. Support for classification is provided by the ROME-Foundation with its criteria catalogue, ROME-III being the most recent one. However, basic approach consists of exclusion of somatic or psychiatric as well as psychosomatic disorders that are sharply defined and readily diagnosable. This article outlines a pragmatic gastroenterological approach by exemplary means of dyspepsia and irritable bowel syndrome. Dyspepsia includes a broad complex of mainly epigastric located symptoms, whereas irritable bowel syndrome is symptomatic with altered bowel habits and mid-abdominal pain in the majority. Gastreoenterologic therapy modalities are mainly based on empirical and symptomatic grounds, more than on precisely explaining pathophysioligic understanding.

Study protocol: Transition from localized low back pain to chronic widespread pain in general practice: identification of risk factors, preventive factors and key elements for treatment--a cohort study

Background Chronic localized pain syndromes, especially chronic low back pain (CLBP), are common reasons for consultation in general practice. In some cases chronic localized pain syndromes can appear in combination with chronic widespread pain (CWP). Numerous studies have shown a strong association between CWP and several physical and psychological factors. These studies are population-based cross-sectional and do not allow for assessing chronology. There are very few prospective studies that explore the predictors for the onset of CWP, where the main focus is identifying risk factors for the CWP incidence. Until now there have been no studies focusing on preventive factors keeping patients from developing CWP. Our aim is to perform a cross sectional study on the epidemiology of CLBP and CWP in general practice and to look for distinctive features regarding resources like resilience, self-efficacy and coping strategies. A subsequent cohort study is designed to identify the risk and protective factors of pain generalization (development of CWP) in primary care for CLBP patients. Methods/Design Fifty-nine general practitioners recruit consecutively, during a 5 month period, all patients who are consulting their family doctor because of chronic low back pain (where the pain is lasted for 3 months). Patients are asked to fill out a questionnaire on pain anamnesis, pain-perception, co-morbidities, therapy course, medication, socio demographic data and psychosomatic symptoms. We assess resilience, coping resources, stress management and self-efficacy as potential protective factors for pain generalization. Furthermore, we raise risk factors for pain generalization like anxiety, depression, trauma and critical life events. During a twelve months follow up period a cohort of CLBP patients without CWP will be screened on a regular basis (3 monthly) for pain generalization (outcome: incident CWP). Discussion This cohort study will be the largest study which prospectively analyzes predictors for transition from CLBP to CWP in primary care setting. In contrast to the typically researched risk factors, which increase the probability of pain generalization, this study also focus intensively on protective factors, which decrease the probability of pain generalization.

Anti-angiogenic therapy for HCC

Hepatocellular carcinoma is an insidious disease that grows without eliciting pain. In the absence of surveillance, the diagnosis of hepatocellular carcinoma is usually made at a late stage, which excludes curative treatments and leaves patients with few therapeutic options. For years, conventional chemotherapy was administered but yielded poor results. This is not surprising since hepatocytes are well equipped to survive exposure to chemotherapeutics. Hepatocytes posses an extensive repertoire of enzymes and pumps capable of degrading and exporting these drugs. Bypassing hepatocytic tumor cells in favour of supportive cells represents an alternative treatment target that has achieved modest success. The supportive cells in the hepatic vasculature comprise endothelial cells and pericytes. Thanks to a concerted effort from fundamental and pharmacological researchers, several drugs targeted to the vasculature are reaching the clinic. This manuscript reviews the rationale for targeting the vascular cells to treat hepatocellular carcinoma, the signalling pathways underlying angiogenesis and the most promising drugs.

Intervertebral disc regeneration or repair with biomaterials and stem cell therapy--feasible or fiction?

The "gold standard" for treatment of intervertebral disc herniations and degenerated discs is still spinal fusion, corresponding to the saying "no disc - no pain". Mechanical prostheses, which are currently implanted, do only have medium outcome success and have relatively high re-operation rates. Here, we discuss some of the biological intervertebral disc replacement approaches, which can be subdivided into at least two classes in accordance to the two different tissue types, the nucleus pulposus (NP) and the annulus fibrosus (AF). On the side of NP replacement hydrogels have been extensively tested in vitro and in vivo. However, these gels are usually a trade-off between cell biocompatibility and load-bearing capacity, hydrogels which fulfill both are still lacking. On the side of AF repair much less is known and the question of the anchoring of implants is still to be addressed. New hope for cell therapy comes from developmental biology investigations on the existence of intervertebral disc progenitor cells, which would be an ideal cell source for cell therapy. Also notochordal cells (remnants of the embryonic notochord) have been recently pushed back into focus since these cells have regenerative potential and can activate disc cells. Growth factor treatment and molecular therapies could be less problematic. The biological solutions for NP and AF replacement are still more fiction than fact. However, tissue engineering just scratched the tip of the iceberg, more satisfying solutions are yet to be added to the biomedical pipeline.

Continuous extradural analgesia in a cow with complex regional pain syndrome

A chronic pain syndrome, similar to the complex regional pain syndrome (CRPS) described in human beings, was diagnosed in a cow with persisting severe pelvic limb lameness. Diagnosis was based on the disproportionate relationship between the severity and duration of pain and the lesion, the failure of conventional analgesic and surgical therapy and the presence of characteristic clinical features. Multimodal therapy, i.e. a mixture of methadone, ketamine and bupivacaine was administered continuously for 17 days via an extradural catheter to counteract nociceptive hypersensitization. Doses were adjusted daily after assessing the effect, using a composite pain score. Physiotherapy was also performed. The diagnosis of CRPS in cattle is unusual. In this case, treatment was successful and the cow was discharged mildly lame and in improving physical condition. Long-term extradural analgesia proved to be safe and effective in the treatment of this syndrome, which was nonresponsive to conventional therapy.

Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia

Muscle pain and weakness are frequent complaints in patients receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin-induced skeletal muscle damage, skeletal muscle biopsies from statin-treated and non-statin-treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin-treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T-tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin-treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro. These findings support the hypothesis that statin-induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable.

Central hypersensitivity in chronic pain: mechanisms and clinical implications

The available literature consistently shows increased pain sensitivity after sensory stimulation of healthy tissues in patients who have various chronic pain conditions. This indicates a state of hypersensitivity of the CNS that amplifies the nociceptive input arising from damaged tissues. Experimental data indicate that central hypersensitivity is probably induced primarily by nociceptive input arising from a diseased tissue. In patients, imbalance of descending modulatory systems connected with psychologic distress may play a role. There is experimental support in animal studies for the persistence of central hypersensitivity after complete resolution of tissue damage. This is particularly true for neuropathic pain conditions, whereby potentially irreversible plasticity changes of the CNS have been documented in animal studies. Whether such changes are present in musculoskeletal pain states is at present uncertain. Despite the likely importance of central hypersensitivity in the pathophysiology of chronic pain, this mechanism should not be used to justify the lack of understanding on the anatomic origin of the pain complaints in several pain syndromes, which is mostly due to limitations of the available diagnostic tools. Treatment strategies for central hypersensitivity in patients have been investigated mostly in neuropathic pain states. Possible therapy modalities for central hypersensitivity in chronic pain of musculoskeletal origin are largely unexplored. The limited evidence available and everyday practice show, at best, modest efficacy of the available treatment modalities for central hypersensitivity. The gap between basic knowledge and clinical benefits remains large and should stimulate further intensive research.

Gender and the relationship between traumatic childhood experiences and pain in adulthood

OBJECTIVES AND METHODS: Gender differences regarding 17 childhood experiences, thought to have traumatising potential (Traumatic Childhood Experiences = TCE), and pain behaviour in adulthood were assessed using a self-administered, anonymously filled-out questionnaire. Patients were consecutively accrued in the offices of practicing physicians. Three research questions were formulated: 1) Are specific TCE reported more frequently in male and female patients with the diagnosis "Pain Associated with Psychological Factors" (PP), compared to patients with "Pain, explained by Organic Processes" (OP), and "Patients with Diseases without Pain" (OD)? 2) Do PP-men and PP-women differ in reporting TCE?; 3) Are specific TCE correlated with Pain Duration, -Intensity and Number of Operations? RESULTS: 1). TCE occurred more frequently in PP-men and PP-women compared to OP- and OD-patients. 2). The PP-women reported much more TCE-items than the PP-men. 3). Duration and Intensity of adult pain associated with psychological factors correlated with certain TCE-items. CONCLUSIONS: The three research questions can be answered by "yes". In patients with pain which has been impossible to diagnose and/or has resisted conventional forms of therapy, TCE (verbal, physical and sexually abusive) have to be looked for, because they often explain adult pain. Unnecessary examinations and surgery can be avoided and therapies can be tailored for the individual patient.

Determinants of reduced walking speed in people with musculoskeletal pain

OBJECTIVE: Maintenance of good walking speed is essential to independent living. People with musculoskeletal disease often have reduced walking speed. We investigated determinants of slower walking, other than musculoskeletal disease, that might provide valuable additional targets for therapy. METHODS: We analyzed data from the Somerset and Avon Survey of Health, a community based survey of people aged over 35 years. A total of 2703 participants who reported hip or knee pain at baseline (1994/1995) were studied, and reassessed in 2002-2003; 1696 were available for followup, and walking speed was tested in 1074. Walking speed (m/s) was used as outcome measure. Baseline characteristics, including comorbidities and socioeconomic factors, were tested for their ability to predict reduced walking speed using multiple linear regression analysis. RESULTS: Age, female sex, and immobility at baseline were predictive of slower walking speed. Other independent risk factors included the presence of cataract, low socioeconomic status, intermittent claudication, and other cardiovascular conditions. Having a cataract was associated with a decrease of 0.10 m/s (95% CI 0.03, 0.16). Those in social class V had a walking speed 0.22 m/s (95% CI 0.126, 0.31) slower than those in social class I. CONCLUSION: Comorbidities, age, female sex, and lower socioeconomic position determine walking speed in people with joint pain. Issues such as poor vision and social-economic disadvantage may add to the effect of musculoskeletal disease, suggesting the need for a holistic approach to management of these patients.

Pain management and the effect of guidelines in neonatal units in Austria, Germany and Switzerland

BACKGROUND: Painful invasive procedures are frequently performed on preterm infants admitted to a neonatal intensive care unit (NICU). The aim of the present study was to investigate current pain management in Austrian, German and Swiss NICU and to identify factors associated with improved pain management in preterm infants. METHODS: A questionnaire was sent to all Austrian, German and Swiss pediatric hospitals with an NICU (n = 370). Pain assessment and documentation, use of analgesics for 13 painful procedures, presence of written guidelines for pain management and the use of 12 analgesics and sedatives were examined. RESULTS: A total of 225 units responded (61%). Pain assessment and documentation and frequent analgesic therapy for painful procedures were performed more often in units using written guidelines for pain management and in those treating >50 preterm infants at <32 weeks of gestation per year. This was also the case for the use of opioid analgesics and sucrose solution. Non-opioid analgesics were used more often in smaller units and in units with written guidelines. There was a broad variation in dosage of analgesics and sedatives within all groups. CONCLUSION: Pain assessment, documentation of pain and analgesic therapy are more frequently performed in NICU with written guidelines for pain management and in larger units with more than 50 preterm infants at <32 weeks of gestation per year.

[On quality of life after surgical therapy of oral cancer - a retrospective multi-center study: the connection between dedentition, denture, quality of life, and dysphagia, and the resulting rehabilitation schemes]

PURPOSE: The surgical treatment of oral cancer results in functional and aesthetical impairments. Patients' quality of life is considerably impaired by oral symptoms resulting from therapy of oral cancer. In many cases the inevitable resection of the tumor, as well as the adjuvant radiochemotherapy will cause the destruction of physiologically and anatomically important structures. One focus of research was the specific rehabilitation of dental loss by functional dentures. Another was the course of 19 impairments (comprehension of speech for unknown others, comprehension of speech for familiar others, eating/swallowing, mobility of the tongue, opening range of the mouth, mobility of lower jaw, mobility of neck, mobility of arms and shoulders, sense of taste, sense of smell, appearance, strength, appetite, respiration, pain, swelling, xerostomia, halitosis). METHODS: Commissioned by the German, Austrian and Swiss cooperative group on tumors of the maxillofacial region (DOSAK), data were collected in 3.894 questionnaires at 43 hospitals in Germany, Austria and Switzerland. The catalogue comprised 147 items in 9 chapters. At the end of the enquiry, 1.761 anonymous questionnaires were returned by 38 hospitals. 1.652 of these could be evaluated regarding the question. RESULTS: The sum score of the 19 impairments was highly increased immediately after the operation and recovered over the next 6 months, without, however, reaching the pre-surgery level. Of 1.652 patients, only 35% did not lose any teeth during therapy. 23% lost up to 5, 17% up to 10 teeth. A quarter of the patients lost more than 10 teeth. The more teeth were lost, the greater the decline of quality of life (p < or = 0.001), although this could be allayed by the functionality of the dentures (p < or = 0.001). There is a reciprocal dependence between the functionality of dental prosthetics and impairment by eating/swallowing (p < or = 0.001). CONCLUSIONS: Patients' quality of life after radical surgery of a carcinoma of the oral cavity depends not only on the functionality of dentures and the specificity of rehabilitation, but also from the initial findings, the extent and location of the resection, the chosen therapy, the general circumstances of the patient's life as well as their strategies of coping. These factors, however, unlike those of functionality of dental prosthesis and rehabilitation, are not modifiable.

[Systematic aspects and therapy of diabetic neuropathy]

Diabetic neuropathy (DN) is an important complication contributing to high morbidity and morbidity of diabetic subjects. Primarily, interventional strategies aim at normalization hyperglycemia (to prevent development and progression of DN), at early diagnosis and at prevention of ulcers and amputations. In addition, an increasing number of pharmaceutical agents is used to symptomatically treat dysesthesia and pain associated with DN. During recent years attempts have been made to pharmacologically treat DN by acting on underlying patho-physiological mechanisms (e.g. sorbitol pathway, non-enzymatic glycation, microvascular abnormalities). So far, these strategies have not changed clinical praxis. This review will give a systematic overview of DN and summarize current pharmacological options to symptomatically treat dysesthesia and pain associated with DN.

Gene and stem cell therapy in peripheral arterial occlusive disease

Peripheral arterial occlusive disease (PAOD) is a manifestation of systemic atherosclerosis strongly associated with a high risk of cardiovascular morbidity and mortality. In a considerable proportion of patients with PAOD, revascularization either by endovascular means or by open surgery combined with best possible risk factor modification does not achieve limb salvage or relief of ischaemic rest pain. As a consequence, novel therapeutic strategies have been developed over the last two decades aiming to promote neovascularization and remodelling of collaterals. Gene and stem cell therapy are the main directions for clinical investigation concepts. For both, preclinical studies have shown promising results using a wide variety of genes encoding for growth factors and populations of adult stem cells, respectively. As a consequence, clinical trials have been performed applying gene and stem cell-based concepts. However, it has become apparent that a straightforward translation into humans is not possible. While several trials reported relief of symptoms and functional improvement, other trials did not confirm this early promise of efficacy. Ongoing clinical trials with an improved study design are needed to confirm the potential that gene and cell therapy may have and to prevent the gaps in our scientific knowledge that will jeopardize the establishment of angiogenic therapy as an additional medical treatment of PAOD. This review summarizes the experimental background and presents the current status of clinical applications and future perspectives of the therapeutic use of gene and cell therapy strategies for PAOD.