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1.
  • Lundin, Anna-Carin (författare)
  • Tendinosis in Trigger Finger
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Trigger finger is one of the most common hand conditions, with a prevalence of almost 3%. The aetiology remains unclear even though many causes have been suggested. The prevailing paradigm is that the pathogenesis of trigger finger is ascribed to primary changes in the first fibrous condensation of the tendon sheath (A1-pulley). Several studies have investigated pathology in the pulley, but few have investigated the tendon. The general aim of this thesis was to find out if there is pathology in the trigger finger tendon and to define it.We first looked at trigger finger tendon biopsies in a light microscope, and found that they were histologically different from healthy tendons. They showed signs of micro-ruptures, collagen degradation, increased amounts of ground substance, both hyper- and hypo-cellular areas, round active cell nuclei and absence of inflammatory cells, all similar to tendinosis. The histological picture was further assessed by using a scoring system for Achilles tendinosis. The trigger finger tendons scored high, suggesting a similar histopathology.Next, we performed a quantitative real-time polymerase chain reaction (qPCR) on trigger finger tendons. We assessed the mRNA expression of 10 genes, which have been described to be differently expressed in Achilles tendinosis (collagen 1 and 3, versican, decorin, biglycan, aggrecan, MMP-2, MMP-3, ADAMTS-5, and TIMP-3). The overall expression pattern agreed with previous studies on Achilles tendinosis, suggesting that the cellular function in trigger finger tendons is disturbed in a similar way as in Achilles tendinosis.Recent experimental and observational research has suggested potential side effects of statin treatment on tendons, but firm evidence was lacking. We performed an epidemiological study on two large population-based cohorts. Statin use was found to increase the risk of both trigger finger and tendinosis in the shoulder and Achilles tendons, especially among men. This suggests a similar pathology in trigger finger and tendinosis.We have also studied the time to treatment effect after a single injection of glucocorticoid in trigger finger. Our results suggest that 60-80% of patients can expect resolution of the triggering within 14 days, and half of them within seven days. This result allows correct information to be given to the patient and proper planning of follow-ups.In conclusion, the pathology in trigger finger tendons is similar to tendinosis in other tendons.
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2.
  • Engstrand, Christina (författare)
  • Hand function in patients with Dupuytren’s disease : Assessment, results & patients’ perspectives
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Dupuytren’s Disease (DD) is a soft tissue disorder that leads to finger joint contractures affecting hand function. DD can be treated with surgery or injection and hand therapy to improve finger joint extension and thereby improve hand function. However, this does not cure the disease and recurrence is common. Previous research on DD has shown improvement in finger joint extension and in self-reported disability of the upper extremity after surgery and hand therapy for DD. However, this provides only a limited perspective on hand function, and multiple dimensions of changes in hand function (i.e. physical, psychosocial aspects and including the patients’ views of results) have not been reported as a whole.Aim: The overall aim of the thesis was to explore hand function before and after surgery and hand therapy in patients with DD, including assessment, results and patients’ perspectives.Methods: The thesis comprises three studies: Study A was a methodological study of interrater reliability in goniometry of the finger joints. Study B was a prospective cohort study with a repeated measures design. Study C was a qualitative interview study, using the model of Patient Evaluation Process and content analysis.Results: Interrater reliability was high or very high for goniometer measurement of finger joint range of motion (ROM) in patients with DD when experienced raters follow our standardized guidelines developed for the study. Changes in hand function consisted of improvement of finger joint extension while active finger flexion was significantly impaired during the first year after surgery and hand therapy. No patient reached a normal ROM, but the majority reached a functional ROM. Sensibility remained unaffected. Patients with surgery on multiple fingers had worse scar pliability than patients with surgery on a single finger. Most patients had their expectations met and were pleased or delighted with their hand function at 12 months after surgery and hand therapy. Safety issues of hand function were of greater concern than social issues. Patients reported less disability and improved health-related quality of life after surgery and hand therapy. The three variables “need to take special precautions”, “avoid using the hand in social context”, and health-related quality of life had significant importance for patients’ rating of functional recovery. Together, these variables explained 62% of the variance in functional recovery. Patients’ perspectives of undergoing a surgical intervention process were described through five categories. Previous experiences of care influenced participants’ expectations of results and the care they were about to receive. Previous experiences and expectations were used as references for appraisal of results, which concerned perceived changes in hand function, the care process, competency, and organization. Appraisal of results could also vary in relation to  patient character. Appraisal of results of the intervention process influenced participants’ expectations of future hand function, health and care.Conclusions: Surgery and hand therapy for DD improve hand function and patients regain a functional ROM needed for performance of common daily activities. Despite the negative effect on finger flexion present during the first year after surgery, patients’ regards their hand function as recovered six to eight months after surgery and hand therapy. Measuring digital ROM in the finger joints with a goniometer is a reliable assessment method. However, from the patient’s perspective, it is not enough to evaluate results only in terms of digital extension or ROM. From their view, results of treatment concern consequences on daily use of the hand, what happens during the care process in terms of interaction between patient and health care provider, as well as their view of the competence and logistics of the organization providing the care.
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3.
  • Svernlöv, Birgitta (författare)
  • Treatment of Epicondylalgia and Nerve Entrapments around the Elbow
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Disorders causing pain in the elbow region is a common problem and is one of the most frequent forms of work-related health problems. These conditions are thus of major importance from the public health point of view, as well as from that of the suffering individual. Both sensory and motor function may be impaired, particularly in cases where a nerve is involved, resulting in severely impaired hand function.“Tennis elbow” (lateral epicondylalgia) has been found to be the second most frequently diagnosed musculoskeletal disorder of the upper extremity in the primary health-care setting. “Golfer’s elbow” (medial epicondylalgia) is not that commonly encountered. It has been stated that tennis or golfer’s elbow syndromes are self-limiting. Even so, clinical experience has shown that there are a few cases where symptoms have a painful and long-lasting course, resistant to many forms of therapy. The outcomes of frequently adopted management regimes for treatment of epicondylalgia or nerve entrapments around the elbow were examined in the following five studies:I: A randomised, prospective study of 38 patients with tennis elbow (lateral epicondylalgia). Groups were assigned to eccentric exercises or stretching. Eccentric exercise gave somewhat better results.In a second part of the study, a 4-year follow-up of 127 patients who used eccentric exercises for tennis elbow was performed. Patients showed decreased pain and increased grip-strength after 3 months treatment. At the time of publication this study was the first to examine eccentric exercises for this condition.II: A retrospective analysis of long-term results from 51 patients treated with surgical release of the common extensor origin because of “chronic tennis elbow”. Eighty-seven per cent of the patients rated themselves as completely recovered or improved.III: A randomised, prospective study of 70 patients with ulnar neuropathy in the forearm (cubital tunnel syndrome). Groups assigned the commonly recommended elbow brace at night or nerve gliding exercises were compared with a control group (information only). The majority of patients improved considerably, both subjectively and objectively, after a 3 months period, regardless of group. The study thus showed the effectiveness of information and expectance, and that orthosis or nerve gliding exercises added nothing further to the result.IV: A retrospective study of 205 patients treated with surgery for suspected nerve entrapment in the forearm. Followup, almost 4 years later, demonstrated a subjective improvement in two of three patients, but only 3% experienced complete relief of all symptoms.V: A prospective long-term study on 20 patients with golfer’s elbow (medial epicondylalgia) treated with eccentric exercises over 3 months. The results showed decreased pain and increased gripstrength. This is the first study published on the management of this disorder with eccentric exercises.
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4.
  • Thurfjell, Niklas, 1977- (författare)
  • p63 – from expression to function : studies of normal oral mucosa and squamous cell carcinoma of the head and neck
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The human p63 gene discovered in 1997 encodes a series of protein isoforms that differ in their N- and/or C-terminal sequences. These isoforms have widely differing properties in promoting or repressing p53-related functions such as growth arrest and apoptosis. In addition, p63 appears to play important roles in the maintenance and differentiation of epithelial cell populations. Many studies have shown that p63, particularly Np63, is expressed in normal epithelium and also highly expressed in squamous cell carcinomas of surface epithelia. Methods. We have refined the analysis of the expression patterns of p63 isoforms by the use of a quantitative RT-PCR technique applied to micro-dissected normal oral mucosal samples. We have also studied p63 expression in squamous cell carcinoma of the head and neck (SCCHN) compared to normal oral mucosa taken from the same patient. Furthermore, tobacco-exposed buccal mucosa was compared to age and gender matched non exposed controls. RT-PCR for telomerase and immunohistochemical analysis for detection of p53 and Ki-67 proteins was further performed. We also explored the function of p63 in SCCHN cells by using small interfering RNA (siRNA) to silence the expression of different p63 isoforms in cell lines originating from SCCHN. The effect of p63 knockdown was studied using a Fluorescein Diacetate based cytotoxicity assay and immunohistochemistry looking at expression of differentiation markers. The response of the siRNA treated cells to radiation and cytostatic drug was also investigated. We have further studied normal oral wound healing using immunohistochemistry and quantitative PCR. By the use of a macro array comparing siRNA treated cells with non-treated cells a possible connection between the BRCA1 gene and p63 expression was shown and further studied with the use of cHIP and luciferase reporter assays. Results. The p63 isoforms are expressed in normal epithelium, with the highest levels consistently found in basal and parabasal layers. Extensive use of tobacco had no effect on p63. The quantitative PCR showed statistically increased levels of the ΔNp63 and p63isoforms. No correlation was found between p63-isoform expression patterns and proliferation. The exploration of the function of p63 in SCCHN cells by the use of small interfering RNA (siRNA) showed a statistically significant decreased survival for tumour cells when all p63 isoforms, the N-terminal truncated or the  isoforms were inhibited. No effect on cell proliferation or expression of epithelial differentiation markers was observed. We also demonstrated that inhibition of p63 expression sensitizes cells to the effects of ionizing radiation and cisplatin. The study of normal oral wound healing using immunohistochemistry and quantitative PCR showed significant changes in p63 isoform expression. The Np63 isoform was mainly expressed in the basal layer in the non proliferating and migrating cells while TAp63 was almost absent. The BRCA1 study showed p63 to bind to the BRCA1 promoter and activate the expression of BRCA1 protein. Summary. The p63 proteins have different functions and the balance between the isoforms and their localisation within the epithelium seems to be important for normal wound healing as well as cancer cell survival.
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