Institute of Clinical Sciences / Institutionen för kliniska vetenskaper

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Kinesiophobia : various aspects of moving with musculoskeletal pain
(2006) Lundberg, Mari
Aim: The overall aim of this thesis was to investigate various aspects of the phenomenon of kinesiophobia among patients with musculoskeletal pain. Study population: For the purpose of this thesis 1304 patients, with musculoskeletal pain, were asked to participate. Of the 1304 patients, 714 (55%) chose to participate. This study population constitutes eight subgroups. Methods and Results: In order to be able to assess kinesiophobia, a reliable and valid measure was needed. Study I evaluated the psychometric properties of the Swedish language version of the Tampa Scale for Kinesiophobia (TSK-SV) questionnaire. The reliability test included stability over time, internal consistency and homogeneity. The test of validity included face validity, content validity and construct validity. The TSK-SV was found to be reliable and evidence supported its validity, although the results indicated a lack of construct validity. An exploratory factor analysis was performed in Study II to explore the conceptual dimensions of the TSK-SV questionnaire based on a large Swedish sample. The findings showed that the TSK-SV measured five different dimensions of kinesiophobia. The aims of Study III were to describe the occurrence of kinesiophobia and to investigate the association between kinesiophobia and pain variables, physical exercise measures and psychological characteristics in patients with musculoskeletal pain. A multiple logistic regression model was preformed to identify associations. Kinesiophobia was a commonly (70%) identified phenomenon in patients with musculoskeletal pain. The results further indicated that kinesiophobia was associated with pain variables, physical exercise measures and psychological characteristics. Study IV explored how patients with persistent musculoskeletal pain experienced moving with pain. The interviews were analyzed according to a qualitative method called the Empirical Phenomenological Psychological (EPP) method. The results were described in three typologies called Failed adaptation, Identity restoration and Finding the way out. Conclusions: In conclusion, TSK-SV can be used prior to the start of a rehabilitation process in order to assess to what extent the patient fears physical movement. It is, however, important to stress that TSK-SV cannot be used as a single measure of diagnosis, but simply gives a rough indication of the level of pain-related fear. This thesis also shows that moving with pain has a deep existential impact on the individual, which needs to be taken into account when treating patients with persistent musculoskeletal pain. Keywords: fear of movement, kinesiophobia, persistent pain, physical therapy, phenomenology, psychometric properties, reliability, validity.
Achilles tendinopathy : evaluation and treatment
(2006) Grävare Silbernagel, Karin
Abstract. Background: Achilles tendinopathy is considered to be one of the most common overuse injuries in elite and recreational athletes. There are, however, only a few randomized studies of treatment and there is a need for standardized outcome measures for the patients’ symptoms and function. Purpose: The overall purpose of this thesis was to develop and evaluate outcome measures and treatment protocols for patients with Achilles tendinopathy. Material, Methods and Results: Initially, a method was developed to evaluate both symptoms and function in Studies I and II. The method was shown to have good reliability in 10 patients with acute Achilles tendon injuries and in 32 patients with chronic Achilles tendinopathy. We questioned, however, the validity of the methods since only small changes were detected while symptoms improved. At that time there was no standardized symptom questionnaire for the assessment of patients with Achilles tendinopathy. A questionnaire of this kind became available in 2001 in English. In Study III this questionnaire, the Victorian Institute of Sports Assessment – Achilles questionnaire (VISA-A), was cross-culturally adapted and evaluated for reliability, validity and structure on 15 healthy subjects and 51 patients. The Swedish version of the VISA-A questionnaire (VISA-A-S), which measured two factors, pain/symptoms and physical activity, was shown to have good reliability and to be a valid instrument, fully comparable to the original version. The VISA-A-S can be used in both research and clinical settings. A test battery for lower leg muscle/tendon function, including jump and strength tests, was developed and evaluated on 42 patients in Study IV. The purpose of the test battery was to evaluate, in more detail than had previously been possible, whether Achilles tendinopathy caused functional deficits on the injured side compared with the non-injured side. The test battery was found to be reliable and able to detect clinically relevant differences in lower leg function between the injured or “most symptomatic” and non-injured or “least symptomatic” sides in patients with Achilles tendinopathy. The test battery imposed more rigorous demands on patient function compared with each individual test. Treatment comprising iontophoresis using dexamethazone combined with exercise for patients with acute Achilles tendinopathy was evaluated on 25 patients in a randomized, double-blind design in Study II. Positive effects on symptoms were found from using iontophoresis with dexamethazone, compared with a control group in patients with acute Achilles tendon pain. Achilles tendon and calf muscle strengthening exercises (intensity modified with the use of a pain-monitoring model) as treatment for patients with chronic (symptoms for more than 2-3 months) Achilles tendinopathy was evaluated in 40 patients in Study I and in 38 patients in Study V. Furthermore, the effect of continued running and jumping on treatment outcome was evaluated in Study V. A treatment protocol which includes Achilles tendon and calf muscle exercises resulted in significant improvements in patients with chronic Achilles tendinopathy. When the pain-monitoring model was used, no negative effects could be demonstrated from continuing Achilles tendon loading activity (such as running and jumping) during treatment. Conclusion: The VISA-A-S questionnaire can be used to evaluate the clinical severity of patients with Achilles tendinopathy and it is useful in both research and clinical settings. Patients with Achilles tendinopathy reports not only pain, but also demonstrate deficits in lower leg function. In the acute phase, the use of iontophoresis with dexamethazone could potentially be beneficial. For patients with both acute and chronic Achilles tendinopathy, the performance of Achilles tendon and calf muscle strengthening exercises with the use of a pain-monitoring model for 6 months can be recommended. A training regimen of continued, pain monitored, Achilles tendon loading physical activity, such as running and jumping, might represent a valuable option for patients with Achilles tendinopathy.
Orbital floor fractures - aspects of diagnostic methods, treatment and sequelae
(2006-06-08T09:00:44Z) Folkestad, Lena
Despite surgical intervention, orbital floor fractures are associated with risks of persisting sensibility disturbances, enophthalmos and diplopia. Cheek asymmetry and trismus may result when the zygoma is dislocated. In evaluating the surgical results patients’ experiences of the outcomes have to be investigated. To investigate sequelae a questionnaire was sent to 107 patients previously treated for an orbital floor fracture (Paper I). Visual analogue scales (VASs) were used in a prospective study (Papers II and III) to assess patients’ experiences of persisting signs and symptoms. The possibility of using electronystagmography (ENG) equipment, normally employed in vestibular testing in ENT practice, for measuring bilateral vertical eye motility was investigated in a methodological study (Paper IV). Fractures were mainly due to assaults and falls. Sequelae were common (83%). A high frequency of diplopia (36%) was associated with antral packing. When stable floor implants replaced this technique, the subsequent prospective study revealed absence of severe cases of diplopia as well as a lower occurrence of diplopia (9.5%). Patients and doctors agreed on the presence of ‘objective’ signs (affected physical appearance and diplopia). Sensibility disturbances and reduced mouth opening capacity were not sufficiently reflected by the diagnostic assessment methods used, and these symptoms were underestimated by the clinicians. Surgery of the internal orbit involves risks. For this reason, operations for purely diagnostic purposes must be avoided. However, 21% of the orbital floor operations in the present study were performed for purely diagnostic purposes. Surgeons did not apprehend the CT scans as being representative of the fracture. No test is at present available that can objectively establish entrapment of soft tissues as a cause of diplopia, although this is an absolute indication for surgery. However, vertical electro-oculography (vEOG) was shown to (i) objectively measure vertical eye motility; (ii) detect and verify mechanical restriction of vertical eye motility; and (iii) distinguish patients experiencing vertical diplopia from healthy test subjects with ‘normal’ eye motility. Both recognition of patients’ experiences and prolonged follow-ups in selected cases are important for treatment feedback, and are prerequisites for improvement of future surgical outcomes. Current diagnostic methods appear to be insufficient. Vertical electro-oculography is suggested as a simple, objective and noninvasive eye motility test with the potential of helping predict which patients will benefit or not benefit from orbital floor surgery.
Sterile water injections and acupuncture as treatment for labour pain
(2006-09-28T14:11:33Z) Mårtensson, Lena
Most women experience pain during labour. Complementary pain relief methods such as sterile water injections and acupuncture are two alternatives for the child birthing women. The lack of knowledge about the use of these methods in clinical practice creates the need to develop and evaluate them. Aims and methods: To elucidate whether the new subcutaneous method of administering sterile water, as well as the previously described intracutaneous injection method, were effective for the relief of labour pain. Ninety-nine women in labour were randomized to either intracutaneous- , subcutaneous injections of sterile water or to placebo (Paper I). To investigate if there was any difference in perceived pain between the intracutaneous and subcutaneous techniques during injection of sterile water. One hundred female volunteers were given injections with both techniques in a cross-over trial (Paper II). To elucidate the clinical use of acupuncture and sterile water injections as pain relief and relaxation during childbirth in Swedish delivery wards. Five hundred and sixty-five midwives answered a questionnaire about their use of these methods (Paper III). To elucidate if there were any differences between acupuncture and sterile water injections in terms of pain relief and relaxation during labour. One hundred and twenty-eight pregnant women in childbirth were randomized to either sterile water injections or acupuncture (Paper IV). Results: Paper I: VAS pain scores were significantly lower in both treatment groups 10 minutes (p=0.001) and 45 minutes (p=0.005) after treatment, compared with the placebo group. Paper II: subcutaneous injections were still perceived as less painful than intracutaneous injections after trial, day and injection location were taken into consideration (p<0.001). Paper III: the midwives’ estimated frequency of administration of acupuncture was much higher than that of sterile water injections, 25 % versus 2 %. The intracutaneous injection technique was more common in clinical practice than the subcutaneous technique. Sterile water injections were used exclusively for pain relief during labour while acupuncture was used for both pain relief and relaxation during labour. Paper IV: women given sterile water injections experience significantly less labour pain and a higher degree of relaxation in labour, compared to women given acupuncture (p<0.001). Conclusions: The results indicate that the subcutaneous injection technique is preferable when using sterile water injections for low back pain during labour. Sterile water injections seem to provide more pain relief and a higher degree of relaxation, compared to acupuncture. However, acupuncture is a more common pain relief method in clinical practice. Key words: Labour pain, pain relief, sterile water injections, acupuncture, survey Correspond with: Lena Mårtensson, RNM, Med. Lic. Fac, School of Life Sciences, University of Skövde, Box 408, SE-541 28 Skövde, Sweden. ISBN-13: 978-91-628-6904-5 ISBN-10: 91-628-6904-3 Göteborg 2006
Inguinal Hernia after Urologic Surgery in Males with Special Reference to Radical Retropubic Prostatectomy. A Clinical, Epidemiological and Methodological Study
(2006-10-02T07:23:39Z) Stranne, Johan
Background and aims: In 1996 the first report indicating that inguinal hernia (IH) was a complication to radical retropubic prostatectomy (RRP) was published. The main aims of this thesis were to further establish this relation, to establish the background incidence of IH in men not subjected to surgery, to identify risk factors for postoperative IH occurrence and to investigate whether postoperative IH is a complication also after other types of surgery performed through a lower midline incision. A further aim was to form a hypothesis regarding the etiology of this complication and explore which methodological considerations have to be addressed when postoperative IH incidence is investigated. Materials and methods: A retrospective patient file survey (PFS) was used on 1039 patients subjected to RRP (n=375 [I] + 664 [III]) and pelvic lymph node dissection for staging of prostate cancer before radiotherapy (PLND) (n=184 [I]). The factors studied in the PFS were post-RRP IH incidence, age at RRP, preoperative IH morbidity, postoperative anastomotic stricture, influence of concurrent PLND at RRP and duration of surgery. From the ongoing Scandinavian Prostate Cancer Group (SPCG) 6 study a database search was used where the annual IH incidence for patients not subjected to surgery (n=953) and patients subjected to RRP (n=152) was investigated (II). Two patient administered questionnaires (PAQ) were also used. One prospective PAQ was sent to patients subjected to RRP (n=207) in whom the postoperative IH incidence was studied and preoperative IH morbidity (III). One retrospective PAQ was sent to patients subjected to PLND (n=88), open prostatectomy for benign prostatic hyperplasia (n=95) and cystectomy (n=76) where the postoperative IH incidence was explored (IV). Results and conclusions: The results show that the incidence of IH within 2 years after RRP is increased at least fifteen-fold as compared to a non-surgical group of patients. The background incidence of clinically overt IHs in men with prostate cancer and a mean age of 69 years is less than 0.5% per year. Increased age and preoperative IH morbidity are risk factors, but postoperative anastomotic stricture, concurrent PLND at the time of RRP and duration of surgery do not seem to increase the risk of post-RRP IH development. The risk of postoperative IH development after other urological procedures in males performed through a lower midline incision seems to be of a similar magnitude as following RRP. The incision per se seems to be the cause of the lesion, probably resulting in a direct disruption of the “shutter mechanism” of the inguinal anulus internus. Constitutional factors predisposing for IH may add to the risk. In the methodological analysis PAQ was found to be superior to PFS to detect previous IH morbidity as well as postoperative IHs.
Studies of Sunscreens: Percutaneous Absorption of Benzophenone-3 and Photostability
(2006-10-20T05:19:47Z) Gonzalez, Helena
Studies of Sunscreens: Percutaneous Absorption of Benzophenone-3 and Photostability Helena Gonzalez Department of Dermatology and Venereology Institute of Clinical Sciences The Sahlgrenska Academy at Göteborg University Göteborg, Sweden Abstract Aim: To learn more about percutaneous absorption of the photoactive compound benzophenone-3 (BZ-3) and to study the excretion pattern of BZ-3 and its metabolite dihydroxy benzophenone (DHB). We also got the opportunity to develop a reverse-phase HPLC method to analyze BZ-3 and DHB. The photostability of seven commercial sunscreens was also studied. Material and methods: Paper I: 11 participants applied a sunscreen, 2 mg/cm2, containing 4% BZ-3. They collected urine for 48 hours after the application. Paper II: 26 participants applied a sunscreen, 2 mg/cm2, containing 4% BZ-3 morning and night for five days. Half of the participants were exposed to UV radiation (UVR). They collected urine for the five days the sunscreen was applied and an additional five days after the last application. Paper III: The assay uses: solid-phase extraction with C8 columns; a Genesis C18 column (4.6 mm x 150 mm ); a gradient acetonitrile-water mobile phase; a UV-detector set at 287 nm. Paper IV: Seven commercial sunscreens were studied with absorption spectrophotometry. Sunscreen product, 0.5 mg/cm2, was placed between plates of silica. The area under the curve (AUC) in the spectrum was calculated for the different UV regions. AUC before (AUCbefore) and after (AUCafter) artificial UV exposure and before and after natural UV exposure were calculated. If the AUC Index (AUCI), defined as AUCI=AUCafter/AUCbefore, was > 0.80, the sunscreen was considered photostable. Results: Paper I: The average total amount excreted was 11 mg, median 9.8 mg, which is approximately 0.4% of the applied amount BZ-3. Paper II: The volunteers excreted 1.2-8.7% BZ-3 of the total applied amount. The mean value found was 3.7%. There was no significant difference between the two groups; p<0.99. Paper III: The assay was linear r2 >0.99, with detection limits for BZ-3 and DHB of 0.01 µmol/l and 0.16 µmol/l respectively. Relative standard deviation was less than 10% for BZ-3 and less than 13% for DHB. The excretion pattern varied among the human volunteers, different patterns were discerned among the individuals. Paper IV: Three sunscreens were unstable after 90 min of natural UV, in the UVA range the AUCI was between 0.41 and 0.76. In the UVB range, one of these sunscreens was unstable with an AUCI of 0.75 after 90 min. Three sunscreens were photostable after 120 min of natural UV, in the UVA range the AUCI was between 0.85 and 0.99 and in the UVB range between 0.92 and 1.0. Conclusions: Paper I: BZ-3 is absorbed by the skin and excreted in the urine after one topical application of a sunscreen containing 4% BZ-3. There are individual differences in the amount excreted and in the excretion pattern. Paper II: Repeated topical applications of a sunscreen containing 4% BZ-3 lead to a higher excretion of BZ-3. There was no statistical difference after exposure to UVR. Paper III: The developed reverse-phase HPLC-method was reliable and suitable to handle a large number of samples. BZ-3 and DHB were excreted in a similar pattern. Paper IV: Three of the seven investigated sunscreens were photounstable in the UVA region. The combination ethylhexyl methoxycinnamate and butyl methoxydibenzoylmethane was unstable regardless of which other photoactive compound that was included in the sunscreen. Key words: benzophenone-3, dihydroxy benzophenone, sunscreens, UV radiation, reverse-phase HPLC, photostability
Transfemoral amputation, Quality of Life and Prosthetic Function. Studies focusing on individuals with amputation due to reasons other than peripheral vascular disease, with socket or osseointegrated prostheses.
(2006-10-27T07:29:04Z) Hagberg, Kerstin
Background: Individuals who have undergone a transfemoral amputation (TFA) due to causes other than peripheral vascular disease (PVD) constitute a sub-group of all amputees. This group is usually of young age at the amputation. Conventionally, prosthetic suspension is achieved with a socket. Using the osseointegration method, prostheses can be attached directly to the bone (OI prostheses) without a socket. Aim: The overall aim was to investigate the health-related quality of life (HRQL) and prosthetic function in persons with a unilateral TFA, due to causes other than PVD, with socket prostheses and OI prostheses. Material, methods and results: General HRQL was assessed using the SF-36. For condition-specific HRQL, a new self-report questionnaire was constructed: the Questionnaire for Individuals with a Transfemoral Amputation (Q-TFA). It provides results for four scores (prosthetic use, prosthetic mobility, problems and global health) and adequate levels of validity and reliability were demonstrated (Paper II). Physical assessments included measurement of the energy cost using the Physiological Cost Index and hip range of motion (ROM). The HRQL and prosthetic function are described for 97 persons (62% male, 38% female, mean age 48 years, mean time since amputation 22 years, cause: 55% trauma, 35% tumour, 10% other) (Paper I). The energy cost was investigated for 41 individuals with socket prostheses (Paper III), while hip ROM was investigated for 43 persons with socket prostheses and 20 with OI prostheses (Paper IV). Finally, prospective results at the two-year follow-up for the first 18 consecutive patients treated with an OI prosthesis within a clinical investigation are reported (Paper V). For the study group (Paper I), the general HRQL was reduced compared with healthy norms. Daily use of the socket prosthesis was reported by 82%. A large number of subjective complaints reducing the HRQL were reported. The most common were heat/perspiration (72%) and sores/skin irritation (62%) with the socket. Further, 48% reported phantom limb pain, 47% back pain and 44% uncomfortable sitting with the prosthesis. The energy cost was increased by 77% compared with controls. The hip ROM was reduced with the socket prosthesis, while individuals with an OI prosthesis had no restriction in hip ROM. Prospective results for the treatment with OI prostheses revealed that 17/18 used the prosthesis and reported an increase in general physical HRQL and more prosthetic use, better prosthetic mobility, fewer problems and better global health at the two-year follow-up compared with the preoperative situation. Conclusions: For persons with an established TFA, for reasons other than PVD, the general HRQL is lower than that of healthy norms and a considerable number of specific problems are perceived. The Q-TFA is a valid and reliable tool for assessments of this population. Treatment with OI prostheses represents a promising development in the rehabilitation of individuals with TFA who report improved general and condition-specific HRQL at the two-year follow-up.
On factors influencing the outcome of various methods using endosseous implants for reconstruction of the atrophic edentulous and partially dentate maxilla
(2006-10-27T07:29:53Z) Becktor, Jonas
Surgical reconstruction of the severely resorbed edentulous maxilla often requires a combination of bone grafts and dental implants. Different methods have been used during the years where donor site, type of bone graft, healing period, timing of implant placement and implant surface have varied. The overall objective of this research work is to evaluate the clinical outcome of such methods when used on a routine basis at one oral & maxillofacial surgery clinic at a county hospital in Sweden. The purpose is also to evaluate the influence of various factors on implant failure. In Paper I, one group of grafted patients (n=64) and one group of non-grafted patients (n=118) were retrospectively evaluated and compared with regard to implant and prosthesis survival. The latter patients had received bone grafts from the iliac crest with simultaneous or delayed (6 months) placement of dental implants with a minimally rough surface (machined/turned). More implant losses were seen in grafted than in non-grafted patients after a mean follow-up of 5 to 6 years, 25% versus 16%, respectively. Most of the implants were lost before loading. There was no difference in prosthesis survival rate. A correlation between the bone volume of the residual jaw bone prior to bone grafting and implant failure rate was seen in the anterior maxilla. There was no difference in implant failure rate between one-stage and two-stage bone grafting and implant placement procedures. The influence of the type of occlusal support on early implant failure in grafted maxillae was evaluated in Paper II. Ninety (90) patients previously treated with bone grafts from the iliac crest and machined/turned implants were included in the retrospective study. The total failure rate was 18%. In comparison, few failures (6.2%) were seen in patients with a removable mandibular denture and the highest failure rate (43.8%) was seen in patients with unilateral occlusal support. Sixteen patients previously treated with 31 zygomatic implants and 74 regular implants in the anterior maxilla as an alternative to bone grafting of the atrophic maxilla were evaluated in Paper III. All implants had a minimally rough surface. Three (4.1%) regular implants were lost and three (9.7%) zygomatic implants had to be removed due to recurrent sinusitis after a mean follow up period of 4 years. All patients received and maintained a fixed bridge. Paper IV evaluated 17 patients subjected to maxillary sinus floor augmentation with blocks of bone from the iliac creast and simultaneous or delayed (6 months) placement of 69 machined/turned implants. After a mean follow up period of 4 years, 8.7% of the implants had been lost. All failures occurred prior to loading of the fixed prostheses. More implants were lost in grafted (10.4%) than in non-grafted (4.8%) areas. Less implants were lost when using a two-stage approach than when using a one-stage technique, 6% versus 18%, respectively. In a prospective study including 61 patients (Paper V), the use of particlated mandibular bone for maxillary sinus floor augmentation and delayed placement of three types of surface modified implants (oxidized, blasted, blasted+acid etched) was evaluated. The majority of patients were treated under local anaesthesia. Two of 180 implants were lost from placement to delivery of the final prosthesis. It is concluded that more implant failures occur in grafted than in non-grafted edentulous maxillae. The bone volume of the residual anterior crest and the occlusal support depending on the type of mandibular occlusion seems to influence the outcome of grafting procedures in the edentulous maxilla. Delayed placement of dental implants in bone grafts seems preferable, at least in partially dentate patients. The use of surface modified implants and particulated mandibular bone may be one way to further improve the results of sinus grafting procedures. The use of zygomatic implants is a viable alternative to bone grafting in the treatment of the severely resorbed maxilla.
On platelet-rich plasma in reconstructive dental implant surgery.
(2006-11-17T08:46:03Z) Thor, Andreas
Abstract Background Severe athrophy of the edentulous maxilla may require augmentation before implants can be placed. Autogenous bone has been used for reconstruction in block or in particulated form. Platelet-rich plasma has been suggested to enhance the healing of bone grafts, as activated platelets release autologous growth factors (GFs) into the wound healing site. Additionally, the GFs of PRP are suggested to enhance the integration of implants into bone. However, controversies exist in the literature with respect to the effect of combining PRP with bone grafts, or implants, as the concept has been evaluated in different study models with a wide range of results. Aims The first two Papers presented, evaluates the effects of PRP in conjunction with autogenous bone grafts and subsequent installation of implants. Paper III explores the thrombogenic properties in vitro of titanium in whole blood and PRP and also evaluates the potential effect of a fluoride titanium surface modification regarding the thrombotic response. Furthermore, a recently developed surgical procedure is evaluated in Paper IV, where simultaneous sinus mucosal lining elevation and installation of implants is performed without the addition of any graft material. Finally in Paper V, an attempt to correlate platelet count, GF release in PRP and its effect on bone formation is performed in a canine peri-implant defect model, where additionally, the modified surface from Paper III is further evaluated. Materials & Methods In Paper I, 19 patients were subjected to autogenous bone grafting from the iliac crest to the maxillary sinus with or without PRP in a split mouth setting. Implants were installed (n=152) after 6 months of healing. Patients were followed with Resonance Frequency Analysis (RFA) and radiological follow-up up to 1 year after loading of implants. 3 months after grafting, biopsies were retrieved and micro implants installed in the grafted site, left to heal for 3 months and thereafter collected with surrounding bone, simultaneously with installation of dental implants. Biopsies from 3 and 6 months were evaluated regarding new bone formation and bone-implant contact in Paper II. In Paper III, in vitro tests with the heparinised slide chamber model were performed. In this model, the tested biomaterial is the only part of a secluded chamber that is not furnished with heparin, and therefore the tested surface is allowed to cause thrombotic reactions in e.g. blood or PRP, that subsequently can be quantified regarding e.g. generation of thrombin and platelet activation. Paper IV consisted of 20 patients, followed clinically and with radiology for a minimum of 1 year. These patients were all subjected to elevation of the sinus mucosal lining, where a bone window was cut out in the sinus wall and replaced after installation of implants (n=44) consequently tenting the mucosal lining. 6 dogs were used in Paper V. Peri-implant defects were created in the mandibles and implants with and without a fluoride titanium surface were installed. PRP or whole blood thereafter filled the defects before closing of the surrounding soft tissues and the dogs left to heal for 5 weeks before collection of samples for histomorphometric evaluations. Results Paper I showed an overall survival rate of 98.7 % after 1 year in function and stable marginal conditions regardless use of PRP or not. RFA disclosed significantly higher values for the PRP side at abutment connection after 6 months but not at the 1 year follow up. Early bone healing was enhanced with PRP as evaluated in biopsies collected from grafts after 3 months of healing, however, no differences were found in biopsies with micro implants after 6 months. Whole blood showed a stronger activation of the coagulation system, in Paper III, and a fluoride modification of a titanium surface seemed to augment the effect. In Paper IV, the survival rate of implants was 97.7% after a minimum of 1 year of evaluation and the average bone gain was 6.51 mm. Marked bone formation was observed around implants also when installed in diminutive amounts of bone. In Paper V, the use of PRP added no significant value to the healing of defects. Regardless of PRP or blood in the defects, a fluoride titanium surface modification enhanced the bone healing significantly. Conclusions This thesis supports the use of PRP in augmentation with particulated autogenous bone due to enhanced early healing and enhanced handling abilities. The use of PRP and implants in combination can not be supported as a result of in vitro and experimental animal studies performed in this thesis. Implant surface characteristics seems to be more important. Bone grafts may be obleviated during sinus lift surgery if the described method is used and will result not only in acceptable results of implant integration, but also in minimising morbidity of patients.
Cerebral palsy in western Sweden - Epidemiology and function
(2006-11-22T11:38:18Z) Himmelmann, Kate
Human ovulation. Studies on collagens, gelatinases and tissue inhibitors of metalloproteinases.
(2006-11-29T06:13:13Z) Lind, Anna Karin
Ovulation is a highly regulated process, which involves the degradation and rupture of healthy tissue of the ovarian follicle and the extrusion of a fertilizable oocyte. This unique biological process is initiated by the LH-surge, which induces major vascular changes and remodelling of the extracellular matrix (ECM) in and around the follicle. The collagens of the ECM make up the tensile strength of the follicle wall and breakdown of these proteins seems to be a prerequisite for follicular rupture to occur. There is now robust evidence that matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) are crucial in this process. Earlier studies in this field have been mostly animal studies. The general aims of this thesis were to investigate the distribution of three types of collagens in the human ovary and to explore the expression patterns of the gelatinases, MMP-2 and MMP-9, together with their endogenous inhibitors, TIMP-2 and TIMP-1, during ovulation. The study was approved by the human Ethics Committee of Sahlgrenska Academy, Göteborg University. Informed written consent was obtained from all women participating in the study. Women, planned for laparoscopic sterilization participated in the study. They were closely monitored by transvaginal ultrasound. Surgery was performed during either of four distinct ovulatory phases and the dominant follicle and its adjacent stroma was excised. Granulosa and theca cells were harvested. Whole ovarian sections from premenopausal women undergoing oophorectomy at surgery for cervical cancer or due to familial predisposition to ovarian cancer were also obtained. The distribution of collagen types I, III and IV in biopsies of the perifollicular stroma from four distinct ovulatory phases as well as in whole ovarian sections was investigated by immunohistochemistry (paper I). Collagen types I and III were abundant in the perifollicular stroma around the periovulatory human follicle. These types of collagen were also present in a typical concentric layered pattern in the stromal capsule of the ovary making up a scaffold for the ovarian tissue. Collagen type IV was present in the basal lamina that separates the granulosa from the theca cells. The staining intensity of collagens type I and III in the perifollicular stroma decreased from preovulatory stage throughout ovulation indicating a degradation of the follicle wall. In paper II-IV, MMP-2, MMP-9 and TIMP-2 and TIMP-1 were found to be present in the stroma-, theca and granulosa cells compartment of the periovulatory follicle. The protein levels of these enzymes and inhibitors were examined by Western Blot in paper II. In paper II-IV mRNA expression was demonstrated by real time PCR and the protein distribution by immunohistochemistry. An increase of TIMP-1 was seen in the perifollicular stroma both on the protein- and mRNA- level. In the granulosa- and theca cells compartments a large increase in TIMP-1 and MMP-9 mRNA was demonstrated. Immunostaining for MMP-2, MMP-9, TIMP-2 and TIMP-1 was visualized in the different compartments of the periovulatory folllcle. In summary, the abundance of collagens in the human follicular wall and their specific localization suggest that major site-directed degradation of collagens is necessary for follicular rupture to occur. This is the first study that has demonstrated an ovulation-associated expression of the ECM remodelling enzyme, MMP-9, together with its endogenous inhibitor, TIMP-1, in and around the human follicle at ovulation. Increasing knowledge concerning these aspects of human ovulation could contribute to the development of clinical treatments of anovulation and also to the discovery of new contraceptive strategies that could inhibit ovulation on the ovarian level without the side effects of the oral contraceptives used today.
Hydrocephalus in children. Epidemiology and outcome
(2007-01-29T12:54:25Z) Persson, Eva-Karin
Aims: To analyse trends in the live-birth prevalence of infantile hydrocephalus and hydrocephalus associated with myelomeningocele (MMC) during the period 1989-2002 and to study the outcome in terms of learning disability, cerebral palsy, epilepsy and visual deficits. Another objective was to explore motor function and disability profiles in various aetiological and gestational-age subgroups and to see whether treatment complications and neuroradiological findings correlate with outcome. Material and methods: A population-based study of all 262 live-born children with infantile hydrocephalus and hydrocephalus associated with MMC born in 1989-2002 in western Sweden. Aetiological and clinical information was collected from medical records, neuroimaging and ophthalmological examinations. A subgroup of 114 children were clinically examined and interviewed. Results: The live-birth prevalence of hydrocephalus was 0.77 per 1,000 live births, 0.48 for infantile hydrocephalus and 0.29 for hydrocephalus associated with MMC. The prevalence of infantile hydrocephalus decreased from 0.55 in 1989 to 0.48 per 1,000 in 2002, while that of MMC decreased from 0.35 to 0.16 per 1,000 during the same period. The prevalence in children born extremely preterm increased dramatically, with a gestationalage- specific prevalence of 13 per 1,000 in 1989 compared with 45 per 1,000 live births in 2002. During the same period, the perinatal mortality in these children decreased from 40 to 15 per 1,000 live births. A ventriculo-peritoneal shunt was the first surgical intervention in 230 children (88%), while an endoscopic ventriculostomy was performed in 31 (12%). At least one surgical revision was required in 64% of the children. Of children with infantile hydrocephalus, 63% had at least one associated impairment, compared with 33% in the MMC group, apart from the consequences of the spinal lesion. Visual and other ophthalmological impairments were identified in the majority of the children. Very preterm birth was associated with a high risk of visual impairment. No child with normal neuroimaging had any associated neurological or visual impairment, compared with eleven of twelve with impairments in children with generalised parenchymal lesions. Conclusions: A decrease in the prevalence of infantile hydrocephalus was noted during the period 1989-1998, but it did not continue in 1999-2002. The stagnation was mainly explained by the increased survival of children born extremely preterm with post-haemorrhagic hydrocephalus. The aetiology of the hydrocephalus and gestational age at birth were important for outcome. The majority of the children had some associated neuroimpairment, such as learning disability, cerebral palsy or epilepsy, and more than three-quarters had ophthalmological abnormalities. Neuroimaging was found to be useful for aetiological, treatment and outcome considerations.
Hydrocephalus in children. Cognition and behaviour
(2007-01-29T14:57:17Z) Lindquist, Barbro
Aims: The main objective of this thesis was to explore the cognitive and behavioural consequences of hydrocephalus in children born at term and preterm, with or without myelomeningocele (MMC) and with or without concomitant neurological impairments, such as cerebral palsy (CP), epilepsy or learning disabilities. Material and methods: From a population-based cohort of all 107 children with hydrocephalus born in 1989-1993, 73 of the surviving children were assessed with intelligence tests and most of them also using behavioural and autism rating scales. Thirty-six of 47 (77%) children with an IQ of ≥ 70 and eight children with MMC but no hydrocephalus were assessed with a neuropsychological test battery (NIMES) and compared with ageand gender-matched controls. Results: One-third of the children were normally gifted (IQ > 85), another 30% had a low-average IQ of 70-84 and 37% had learning disabilities (IQ < 70). An IQ of < 70 was found in 42% of children without MMC and in 29% of those with MMC. Children born preterm had a lower IQ than those born at term. Children with CP and/or epilepsy had significantly lower IQ scores than those without these impairments. Parents rated 67% and teachers 39% of the children as having behavioural problems. Learning disabilities increased the risk significantly. Almost all the children with CP and/or epilepsy had behavioural problems. Learning disabilities, CP and epilepsy significantly increased the risk of autistic symptoms, which were present in 13 %, in 4 % of those with MMC and in 20 % of those without MMC.. Children with hydrocephalus both with and without MMC and with an IQ of > 70 performed significantly less well than controls on learning, memory and executive functions but not on registration skills. There were no differences between children with hydrocephalus in combination with MMC and those without MMC, whereas children with MMC but no hydrocephalus and normal intelligence performed as well as controls on all the neuropsychological functions. Conclusions: The majority of children with hydrocephalus had learning disabilities or a low-average IQ, as well as behavioural problems, and some had autistic symptoms. Despite average or slightly below average intelligence, children with hydrocephalus had major difficulties with learning and memory and with executive functions, regardless of the aetiology of the hydrocephalus. Only MMC did not appear to influence cognitive and neuropsychological outcome as much as the brain lesion causing or caused by the hydrocephalus.
On the influence of micro-and macroscopic surface modifications on bone integration of titanium implants
(2007-01-31T12:34:30Z) Miranda Burgos, Patricia
Background: Osseointegrated titanium implants are routinely used in clinical denstistry as anchorage units for dental prostheses. Although the overall clinical results are good, there are clinical situations when an optimized implant healing is desirable, for instance in order to shorten healing periods and to allow immediate loading. Aims: The present work was undertaken to study the influence of some micro- and macroscopical surface modifications on the integration and stability of titanium implants in bone. In addition, the aim was also to study the influence of a bone growth factor and autogenous bone grafts on implant healing in bone defects. Materials & Methods: The thesis is based on five experimental studies using a total of 12 mongrel dogs and 39 New Zealand White rabbits. In total, 327 screw-shaped implants were evaluated with histology and biomechanical tests. The implants had either a turned surface or had been treated with anodic oxidation to create a porous surface structure (microscopic modification). A groove with various sizes was added to one thread flank of oxidized implants (macroscopic modification) for comparison with implants without a groove. Ground sections of the intact bone-titanium interface were prepared for light microscopy and quantitative morphometry. A micro-CT technique was used for 3D visualisation of the bone in relation to the implant surface. Implant stability was measured with removal torque (RTQ) tests and resonance frequency analysis (RFA) measurements. Results: Turned and oxidized implants were placed in the dog mandible with circumferential defects which were filled with dog BMP+ carrier, carrier alone, autogenous bone chips or nothing. No differences in histological response and implant stability were seen between the different materials and controls after 4 and 12 weeks of healing. However, oxidized implants shower a stronger bone tissue response and were significantly more stable than turned implants after 4 weeks. A rabbit study demonstrated direct bone formation at the surface of oxidized but not turned implants after 7, 14 and 28 days. A darkly stained layer became populated with osteoblasts which produced osteoid towards the implant surface whilst turned implants seemed to be integrated by approximation of bone from the surrounding bone and marrow tissues. In paper III, an increased resistance to RTQ was seen for oxidized implants with a 110μm wide and 70 μm deep groove as compared with control implants without a groove after 6 weeks of healing. This was not observed for 200 μm wide grooves. Histology showed an affinity of bone formation to the grooves. Paper IV evaluated the influence of three different groove sizes on implant stability as measured with RTQ and RFA. The results confirmed that 110 μm grooves resulted in better stability than implants with 80 μm or 160 μm wide or no grooves. Histology of RTQ specimens revealed an increased incidence of bone fracture at the entrance of the groove as opposed to a separation at the bone-implant interface with decreased groove width. Bone formation had an affinity to the grooves which increased with decreased groove width. In paper V, bone formation was seen to occur more frequently in grooves than on opposing flank surfaces after 7, 14 and 28 days of healing in implant sites with small bone volumes. Conclusions: The present thesis shows that both micro- and macroscopical surface modifications have positive influences on the bone tissue response and stability of titanium implants. It is suggested that this is due to a combination of (i) contact osteogenesis as stimulated by the microtopography and (ii) guided bone formation as stimulated by the macrotopography, which resulted in an improved mechanical interlocking between bone and implant surface.
Studies on pathophysiological mechanisms in experimental models of acute renal failure
(2007-02-19T07:35:24Z) Nitescu, Nicoletta
Acute renal failure (ARF) affects 5-20 % of critically ill patients and is an independent risk factor for death in this patient population. Reactive oxygen species, thrombin and endothelin-1 (ET-1) are increased in ARF, and could contribute to the development of kidney failure and the poor prognosis. The aim of these studies was to investigate the effects of N-acetylcysteine (NAC; an antioxidant), thrombin inhibition and ET-1 receptor blockade on renal hemodynamics and function in experimental models of ischemic and septic ARF in rats. N-acetylcysteine was studied in a model of renal ischemia-reperfusion (IR) injury induced by renal arterial clamping. N-acetylcysteine improved glomerular filtration rate (GFR) day 1 and 3 after IR. Furthermore, NAC decreased renal interstitial inflammation. N-acetylcysteine-treated rats had preserved renal glutathione levels and decreased plasma ascorbyl radical concentrations, indicating improved intrarenal antioxidant capacity and attenuated systemic oxidative stress. However, NAC did not improve GFR, total renal blood flow (RBF), or cortical (CLDF) and outer medullary (OMLDF) perfusion measured by laser-Doppler flowmetry, during the first 80 minutes after IR. Thrombin inhibition with melagatran was examined in endotoxemia induced by lipopolysaccharide infusion, and in renal IR. During the first 3 h of endotoxemia, melagatran improved OMLDF, but did not attenuate the decline in GFR, RBF, CLDF and mean arterial pressure (MAP). In addition, melagatran attenuated the increase in plasma concentrations of aspartate aminotransferase, alanine aminotransferase and bilirubin, and of the cytokine tumor necrosis factor (TNF)-alpha. Melagatran did not diminish hepatocellular necrosis or the elevated hepatic gene expression of TNF-alpha, inducible nitric oxide synthase and intercellular adhesion molecule-1, evaluated by reverse transcription-polymerase chain reaction. In renal IR, melagatran did not ameliorate the decline in renal function, or attenuate renal histopathological abnormalities. We studied the renal effects of selective endothelin type A (ETA), and type B (ETB), receptor antagonists during the first 2 h of normotensive endotoxemia with acute renal dysfunction. In saline-treated rats, endotoxin induced an approximate 40 % reduction in GFR, without significant changes in MAP, RBF, or in cortical perfusion and pO2, measured by oxygen sensitive microelectrodes. In addition, endotoxin increased outer medullary perfusion and pO2. Neither selective, nor combined, ETA and ETB receptor blockade improved GFR. However, in rats receiving selective ETB receptor antagonist, or combined ETA and ETB receptor blockade, endotoxin produced marked reductions in RBF and CLDF, without affecting MAP. In conclusion, NAC is renoprotective in renal IR presumably by decreasing renal oxidative stress and inflammation, but not by improving kidney hemodynamics early after the ischemic insult. Thrombin seems not to be an important pathogenetic factor in the development of renal IR-injury. Thrombin inhibition with melagatran during endotoxemia preserves renal outer medullary perfusion, ameliorates liver dysfunction and attenuates the systemic inflammatory response. Endothelin-1 has beneficial effects on renal hemodynamics during early normotensive endotoxemia by activation of ETB receptors that exert a renal vasodilator influence and contribute to maintain normal RBF.
Tight juntion in ovarian surface epithelium and epithelial ovarian tumors
(2007-03-22T07:22:22Z) Yihong, Zhu
Epithelial ovarian cancer originating from ovarian surface epithelium (OSE) is the most lethal type of gynecological cancer among women worldwide. The poor understanding of the cellular and molecular events associated with ovarian carcinogenesis leads to difficulties in early diagnosis and in efficient treatment. Recently, much evidence has implicated that tight junction (TJ) could play a role in signaling pathways that regulate cell proliferation, polarization, and differentiation. Moreover, altered expression of TJ proteins have been discovered in many types of human epithelial tumors. The general aims of this thesis were to investigate the expression, localization, function and modulation of TJ in normal OSE and epithelial ovarian tumors (EOT). Moreover, a further understanding of the possible roles of TJ in transformation of OSE towards EOT and in tumor progression was sought. The studies were approved by the human Ethics committee of Sahlgrenska Academy, Göteborg University. Informed written consent was obtained from all women participating in the study. Cultured OSE, EOT biopsies and cell lines were used in the studies. Formation of TJ was investigated by electron microscopy observation, immunofluorescence and western blot with semi-quantitative densitometry analysis. Ion-barrier function of TJ was evaluated by trans-epithelial resistance (TER) measurement. The results showed that: 1. TJ proteins ZO-1, occludin and claudin-1 are expressed in normal OSE cells in situ and in vitro. TJ structure was confirmed by electron microscopy observation in early passage of cultured OSE. During culture of normal OSE, a low TER value was built up and could be interfered with by a Ca2+ chelator. 2. Claudin-3 and -4 were de novo expressed or up-regulated in ovarian epithelial inclusion cysts and EOT compared with normal OSE. Moreover, in ovarian serous and mucinous tumors, claudin-4 was significantly increased in borderline-type tumors and adenocarcinomas compared with benign tumors. Claudin-3 was significantly increased in adenocarcinomas compared with borderline-type and benign tumors; whereas no changes were found for claudin-1 or -5. 3. In the study of four ovarian cancer cell lines, ZO-1, claudin-1, -3, -4 and E-cadherin were found to be expressed along the entire cells periphery in serous adenocarcinoma cells concomitant with high TER value, while clear-cell and endometrioid adenocarcinoma cell lines did not express claudin-4 and E-cadherin, concomitant with minimal TER values. 4. When transforming growth factor (TGF)-β1 was added to cultured OSE and OVCAR-3 ovarian cancer cell line, the expression levels of TJ and adherens junction (AJ) proteins and TER values were changed. Furthermore, treatment with TGF-β1 also induced EMT-like morphological change in cultured OSE. It is concluded that normal OSE forms TJ with a weak ion-barrier function. The TJ proteins claudin-3 and -4 are up-regulated in EOT. Specific function of TJ might depend on and differ in between various histological subtypes of ovarian cancer. TGF-β1 can modulate the formation of TJ and AJ, and the ion-barrier function of TJ in both OSE and epithelial ovarian cancer cells in culture. These findings suggest a potential role of TGF-β1 in epithelial ovarian tumorigenesis.
Virtual Reality Simulations and Interventional Radiology
(2007-03-26T06:06:42Z) Berry, Max
INTRODUCTION: Use of virtual reality (VR) simulators in endovascular interventional education has become increasingly popular yet many questions surrounding this nascent technology remain unanswered. While progress has been made in other disciplines such as endoscopy and minimally invasive surgery, scientific evidence investigating endovascular simulations remains limited. The general aim of this dissertation was to conduct validation studies to elucidate the potential for skills acquisition and assessment outside of the catheterization laboratory using VR simulation. Endovascular skills transfer from VR-Lab to the porcine laboratory (P-Lab) was also investigated. An economic analysis was performed to assist in the establishment of a realistic VR implementation strategy. MATERIALS AND METHODS: Simulator validations were conducted by comparing performance metrics collected from novices and experienced physicians using Student’s t-test. Performance metrics were recorded by the simulator while participants treated simulated patients suffering from renal artery stenosis (RAS) and carotid artery stenosis (CAS). Endovascular skills transfer was tested using the P-Lab as an approximation of the human catheterization laboratory. A group of endovascular novices were evaluated in the P-Lab and the VR-Lab using an objective skills assessment of technical skills (OSATS), yielding a Total Score. Participants were then randomized into different training groups, put through their assigned training schema and subsequently re-evaluated in both laboratories. ANCOVA analysis was conducted to compare the cumulative effect each type of training had on Total Score. Consumable and rental fees from the skills transfer study were used to calculate the comparison data for the economical analysis. RESULTS: Face validity was demonstrated for both the renal and carotid artery stenosis modules. Neither construct validity study produced results which differentiated between the expert and novice performance metrics except for fluoroscopic and procedural times. VR-Lab training sessions generated skills which improved P-Lab performances. VR-Lab training cost less than the P-Lab using our economical analysis. CONCLUSIONS: Despite demonstrating face validity, VR-Lab simulations should not be used alone for skills assessment outside of the catheterization laboratory in its present form. Skills learned in virtual reality transfer favorably to the P-Lab and simulation training seems to offer a viable alternative of non-clinical training. The VR-Lab affords a more economical method to teach and practice endovascular skills compared to the P-lab. Further research is needed to elucidate the relative efficacies of both training methods
Obstetrical Brachial Plexus Palsy
(2007-03-27T08:55:10Z) Mollberg, Margareta
OBSTETRICAL BRACHIAL PLEXUS PALSY Margareta Mollberg Department of Obstetrics and Gynaecology, The Institute for Clinical Sciences, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden Background: Obstetric brachial plexus palsy (OBPP) at birth is one important cause of neurological disability in children and adults; the incidence has increased substantially in Sweden over the past decade. Several risk factors for OBPP have been identified, e.g. high birth weight and shoulder dystocia, but it remains difficult to predict based on antenatally available information. Despite extensive research on OBPP, there is no generally accepted strategy for prevention. The overall objective of this thesis is to study predisposing risk factors for OBPP in vaginally delivered infants and to identify specific obstetric procedures that are strongly associated with OBPP. Based on this knowledge, our ultimate aim is to develop a prevention strategy with respect to manual assistance in the second stage of labour. Methods: Paper I reports on a retrospective case-control study aimed at investigation of the incidence and risk factors for OBPP in a large population studied in 1987-1997. All deliveries recorded in the Swedish Medical Birth Register during the period were investigated. Cases of OBPP were compared with all cases without OBPP. Paper II describes a retrospective case-control study, the purpose of which was to identify risk factors for OBPP, specifically in women delivered by vacuum extraction. The groups with and without OBPP were compared with regard to possible risk factors, including those linked to the vacuum extraction procedure. The aim of the prospective population-based case-control study presented in Paper III was to evaluate the association between OBPP and obstetric manoeuvres during the second stage of delivery. Obstetric management in OBPP cases was compared to management in a randomly selected control group. Paper IV and Paper III are based on the same cases. The aims of the study presented in Paper IV were a) to describe neurological deficits in children with remaining OBPP at 18 months of age; b) to compare maternal, infant and obstetric data in infants with and without OBPP at 18 months of age and c) to evaluate if differences in force applied in downward traction of the head (ranked on a 100-point visual analogue scale) correlated to the number of affected nerve roots (C5-C6, C5-C7, C5-Th1). Results: The incidence of OBPP in Sweden increased from 0.17% to 0.27% between 1987 and 1997. Infants with high birth weight, especially >4500 g, were at increased risk of shoulder dystocia and OBPP. However, high birth weight was not or only weakly over- represented among children with persistent OBPP, compared with those who recovered, suggesting that other factors are important. Hence, many factors related to prolonged second stage and difficulties in delivering the shoulders were overrepresented in the OBPP group, compared to controls. In particular, forceful downward traction applied to the head after the fetal third rotation represented an important risk factor for OBPP in cephalic-presentation vaginal deliveries. Downward traction of the head had been applied more often and with greater force in the group with persistent damage and there was a significant correlation between the force used and the number of affected nerve roots. Conclusion: We have confirmed that well known factors such as birth weight and shoulder dystocia are indeed important risk factors for OBPP. Furthermore, obstetric procedures, especially forceful downward traction of the head, conferred additional risk of OBPP at birth, as well as at follow-up at age 18 months. Our data suggest that forceful downward traction of the head should be avoided and indicate that other measures should be taken to release the impacted shoulder, e g. maximal flexion of the maternal hips, rotation of the shoulders and/ or extraction of the posterior arm.
Open and closed endotracheal suctioning. Experimental and human studies.
(2007-04-20T06:11:16Z) Lindgren, Sophie
Background: The practice of endotracheal suctioning of ventilator treated patients is necessary to remove secretions to prevent obstruction of the endotracheal-tracheal tube and lower airways. This very common procedure creates a large variety of heart-lung interferences. The closed system enables ventilation during suctioning, avoiding disconnection from the ventilator. Thus, the lesser side-effects of the closed suction system have been thoroughly evaluated rather than its effectiveness of secretion removal. Qualitative and semi-quantitative studies have indicated that the effectiveness of the closed system is inferior to the open one. Optimising the side-effects and effectiveness of the suction procedure is essential to preserve oxygenation in critically ill patients. This also requires adequate monitoring techniques. Suctioning through a fiberoptic bronchoscope (FOB) via a tight seal connector is another form of closed suctioning. The aim of this thesis was to evaluate the effectiveness and side-effects of open and closed suctioning manoeuvres, using novel lung-monitoring techniques. Methods: Studies were performed in mechanical lung models, an experimental model of acute lung injury (ALI) in pigs and in ALI patients. Effectiveness of secretion removal was evaluated by weighing the suction system before and after suctioning of gel in a transparent trachea. In ALI model and patients, airway pressure and lung mechanics were measured via a tracheal catheter. A modified N2 wash-out/wash-in method was used for functional residual capacity (FRC) measurements. Electric impedance tomography (EIT) was used to monitor global and regional lung volume changes during different suction manoeuvres. Results: In a mechanical lung, closed suction during volume control ventilation caused high intrinsic PEEP levels at insertion of the catheter. Pressure control ventilation (PCV) produced less intrinsic PEEP. The continuous positive airway pressure (CPAP) mode offered the least intrinsic PEEP during insertion of the catheter and least sub-atmospheric pressure during suctioning. Open suctioning and closed suctioning during CPAP of 0 cmH2O was about five times more effective in regaining gel from an artificial trachea than closed suctioning during PCV or CPAP of 10 cmH2O. In lavaged lungs side-effects were considerable less during closed suction with positive pressure ventilation than during open suction. Closed system suctioning during CPAP of 0 cmH2O caused side-effects similar to open suctioning. At disconnection FRC decreased with about 50 % of baseline value and further 20 % during open suctioning. Regional compliance deteriorated most in the dorsal parts of the lavaged lung. Post-suction restitution of lung volume and compliance was somewhat slower during pressure controlled - than during volume controlled ventilation, both in experimental lung injury and in some ALI patients. Bronchoscopic suction through a tight seal connector in a mechanical lung and in ventilator treated ALI patients caused marked lung volume reduction, especially if the endotracheal tube was too small in relation to the thickness of the bronchoscope. Conclusions: New monitoring strategies such as continuous, bedside FRC measurements with EIT technique and the nitrogen washout/washin method could contribute to a better understanding of the suctioning induced lung collapse and give us knowledge on how to minimize its negative effects, hence develop better clinical routines for handling them. The largest loss of lung volume takes place already at disconnection of the ventilator prior to suctioning. The dorsal regions of lavaged lungs are most affected by disconnection and suctioning. Closed system suctioning prevents lung collapse but is less efficient in removing secretions. Volume control ventilation in the post-suctioning period is a way of recruiting collapsed lung tissue. Bronchoscopic suctioning can cause severe lung collapse, although considered a closed system.
Aspects on the management of patients with esophageal cancer
(2007-05-21T07:19:04Z) Bergquist, Henrik
Cancer of the esophagus is assessed to be the 8th most common cancer form in the world, with approximately 460.000 new cases annually. It is often diagnosed at a late stage, is related to severe morbidity and a poor prognosis, why treatment frequently has a palliative aim with the main objective to relieve dysphagia. The present thesis aims to explore some of the questions related to the management of these patients. The two most common palliative strategies today, i.e. stent-treatment and brachytherapy, were compared in 65 patients with incurable cancer of the esophagus or gastro-esophageal junction (GEJ). Stent-treatment was found to offer a more prompt effect on dysphagia and was more cost-effective than brachytherapy. On the other hand, brachytherapy offered a less pronounced deterioration of health-related quality of life (HRQL) and an equal relief of dysphagia after 3 months, why it gives a viable alternative in patients with a longer survival (Paper I+II). To evaluate if survival can be predicted, 96 patients with newly diagnosed incurable cancer of the esophagus or GEJ were included and their clinical variables and HRQL data were analyzed. In a univariate analysis, Karnofsky Index, M-stage, tumor-stage, CT derived size assessment of the primary tumor and 10 of 25 scales and items of the HRQL questionnaires (EORTC QLQ-C30 and QLQ-OES18) were found to relate to survival. However, in a multivariate analysis, only M-stage, physical functioning, fatigue and reflux scale were found to be independent predictors. Internal validation of the established predictors showed a high level of reliability (Paper III). Psychiatric morbidity in patients with cancer of the esophagus or GEJ has previously not been evaluated. At diagnosis and during one year, we screened for anxiety disorder and depression in 94 patients with all stages of the disease using the HADS questionnaire. Anxiety and/or depression was found to be common at diagnosis (42% of the patients), regardless of sociodemographic background, tumor-stage or therapy given. The proportion of patients with anxiety disorder decreased during the first two months compared to at diagnosis (34%), while the proportion of patients with depression was comparatively stable over time (29% at diagnosis). Depression was, however, more common among patients who died during the study period compared to the survivors (Paper IV). The long-term clinical and functional outcome of radical surgery with pharyngolaryngo¬esophagectomy and jejunal transposition following chemoradiotherapy in patients with proximal esophageal or hypopharyngeal cancer was evaluated. Promising long-term results with regard to survival was found. In addition, a generally good HRQL and mild dysphagia was found, in spite of a generally poor speech valve function and disturbed bolus-passage according to radiological evaluation (Paper V+VI).

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