| 1. |
- Hellgren, Johan, 1966-
(författare)
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Compensation for hearing loss and cancellation of acoustic feedback indigital hearing aids
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The development of integrated circuits during the last decades has made it possible to incorporate digital signal processing in hearing aids that fit into the ear canal and are powered by small zink-air batteries. The digital signal processing provides new possibilities for the hearing aid to modify the signal to fit the impaired ear. A linear phase filter bank that is intended as a basic building block of the signal processing in digital hearing aids is introduced in this dissertation. The filterbank is computationally very efficient and divides the input signal into a number of narrow band signals for further signal processing. The filter bank was combined with band specific gains and two compressors to form the signal processing of a hearing aid. The compressors allow leveldependent gain. Three alternative fitting strategies used to adjust the characteristics of this hearing aid to the individual hearing impaired listener were evaluated. The three fitting strategies differed mainly in the characteristics of the compressors. The strategies were evaluated by hearing impaired subjects in a field test and in laboratory tests. When the subjects were grouped according to their preference among the fitting strategies, the results showed significant differences in the hearing loss configuration between the groups.One of the main tasks of a hearing aid is to amplify the signal to make it audible for the hearing impaired user. The maximum gain that can be used in a hearing aid will be controlled by the feedback from the output to the microphone, as the hearing aid will be a part of a closed loop system. The feedback path depends on several factors such as the position of the microphone (differs between hearing aid categories), size of vent, and the acoustics around the hearing aid. The feedback, and thus the maximum gain that can be used in a hearing aid, has been identified with a number of different hearing aids in a number of conditions that can be expected when the hearing aid is used under real-life conditions.Feedback cancellation can be used to reduce the negative effects of feedback on the performance of the hearing aid. An internal feedback in the hearing aid that is an estimate of the external feedback is then used to cancel the feedback signal. The external feedback path will vary as the hearing aid is used ( e.g. when a telephone set is placed by the ear). It is thus desirable to continuously identify the feedback path. One approach to do this is to utilize closed loop identification with the direct method and some recursive identification method. The output and input signals of the hearing aid are then considered as input and output signal of the system to be identified, i.e. the feedback path. An advantage with this method is that the identification can be done without modifying the output signal. A drawback is that the estimate may be biased, depending on the characteristics of the input signal. A difference from many other closed loop identification problems is that the data used for identification will depend on previous estimates of the system. A feedback cancellation algorithm where Filtered-X LMS is used with the direct method has been analyzed. Filtered-XLMS is computationally efficient and gives a possibility to incorporate known characteristics of the feedback path in the model set used. Prefiltering was also used in the algorithm as it can provide an unbiased estimate if the spectrum of the input signal is known.
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| 2. |
- Adell, Gunnar, 1953-
(författare)
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Indicators of colorectal cancer prognosis and response to preoperative radiotherapy
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer is one of the three most common malignant diseases in Sweden, with about 5,000 new cases each year. Thirty-five percent of these are rectal cancer, for which local recurrence after surgery has been a serious problem. The five-year survival rate in colorectal cancer has improved from about 40% in 1960 to 55% in 1995. Adjuvant chemotherapy of colon cancer, preoperative radiotherapy and improved surgical techniques in rectal cancer have contributed to the improved results. To select patients best suited for pre- or postoperative therapy, we need indicators of both prognosis and response to therapy.Using antibodies against cytokeratin, we found that 39% of patients with colorectal carcinoma that had penetrated the muscularis propria but without lymph-node metastases by routine light microscopy, had got micrometastases. Survival among patients with micrometastases was not significantly different from that among patients without such metastases.We also identified subsets of tumour-infiltrating mononuclear cells and studied their pattern of distribution in relation to regressive tumour areas and Dukes class. Our interpretation is that the subsets of tumourinfiltrating mononuclear cells change with advancing Dukes class, indicating gradual deterioration of the local immune control.We also investigated the interaction between p53, Ki-67, apoptosis and the outcome in rectal cancer with and without short-term preoperative radiotherapy. The expression of nuclear p53 protein seemed to be a significant predictive factor for local treatment failure after preoperative radiotherapy. Low tumour cell proliferation measured with Ki-67 in the preoperative biopsy correlated with improved local control and disease-free survival after preoperative radiotherapy.High apoptotic index was associated with improved local control of rectal cancer even without pre-operative radiotherapy, whereas local control of tumours with low and intermediate apoptotic index was significantly improved by preoperative radiotherapy.In conclusion, micrometastases in regional lymph nodes are an interesting phenomenon but with limited prognostic value. The subsets of tumour-infiltrating mononuclear cells change with advancing Dukes class, and its seems that the local immune control is gradually broken down. In rectal cancer, p53 expression, tumour proliferation measured with Ki-67 and apoptotic index seem to be interesting indicators of rectal cancer prognosis and response to preoperative radiotherapy.
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| 3. |
- Almroth, Gabriel, 1953-
(författare)
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Immunoglobulins, immunoglobulin subclass-distributions and serologic markers in some renal and systemic disorders
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this study we evaluated pathogenetic factors and possible mediators of renal and systemic disorders where immunologic mechanisms might be of importance.An abberant immunoglobulin and IgG-subclass distribution was detected in 103 patients with primary and secondary glomerulonephritis as well as in 38 patients with the systemic disease primary Sjögren 's syndrome or purpura hypergammaglobulinemica (elevated IgG1 and low IgG2 ).The drug hydralazine, an anti-hypertensive, was considered to cause renal disease on an immunologic base in 17 patients, with autoantibody production (mainly ANA and antibodies to myeloperoxidase).Dialysis-patients showed adequate antibody responses to vaccination against pneumococci but low responses against hepatitis B, while the IgG-subclass response of the hepatitis B antibody (anti-HBs) was low, but not shown to be significantly different from that of healthy adults.A therapeutical removal of igG-antibodies with immunoadsorption or plasmapheresis was considered to have a possible adjuvant effect to medical immunosuppressive treatment alone in 44 patients with rapidly progressive glomerulonephritis.Hepatitis C virus (HCV) is common in dialysis patients and renal transplant recipients. In 20 anti-HCV positive sera from 1988-91 recombinant immunoblott assay (RIBA) was positive in 8 cases and indeterminate in 7, while HCV RNA was present in 13/20 tested sera. In October 1991 17% of our hemodialysis patients were verified or suspected carriers while 11% were verified or suspected carriers in January 1997. Genotype 2b was found in 13/24 tested cases and in 7 amplifiable 2b sequences a strong phylogenetic relationship occurred. In 8 out of 12 RIBA-3 indeterminate sera HCV-RNA was still positive. Awareness and preventive measures limited transmission between patients.Indeterminate RlBA-results should, also with modem assays, be regarded with caution due to the relative immunodeficiency of uremic patients.In conclusion renal and systemic diseases may affect the serum immunoglobulins and immunoglobulin G-subclasses, while a study of the specific antibody subclass distributions (anti-HBs) showed no difference in renal (dialysis) patients and healthy adults. Medication (hydralazine) and infection may be triggering factors of various forms of glomerulonephritis. Uremia affects the antibody responses to hepatitis C in dialysis patients. The extent of renal disease as well as the possibility of therapeutic removal of antibodies is also important for the immunologic responses of such disorders.
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| 4. |
- Bachrach-Lindström, Margaretha, 1957-
(författare)
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Nutritional status and functional capacity in elderly people with hip fracture
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim was to study nutritional status and functional capacity in elderly men and women admitted to hospital with a hip fractnre, and to evaluate the effect of nutritional intervention and surgical method. A total of 176 patients participated in the study. Of them 84 received protein- and energy-enriched meals at hospital and nutritional advice on discharge and at home. A total of 100 patients with displaced femoral neck fracture were randomised to treatment with either total hip arthroplasty or osteosynthesis with Olmed® screws.The patients were examined and interviewed the first time within 4-6 days after surgery, as well as one and three months aud one year after surgery. The nutritional status was assessed with body mass index, measures of triceps skinfold thickness, estimation of muscle mass and body composition. Serum albumin, insulin-like growth factor-I and hormones were measured. Functional capacity was assessed with the Modified Norton scale, Katz index of ADL and a questionnaire measuring instrumental activities of daily living.Mentally impaired patients had worse nutritional status aud functional condition compared with the lucid group at inclusion, deteriorated more in activity and mobility fimctions and had a higher one-year mortality rate. The nutritional intervention was not powerful enough to have effect on anthropometric or biochemical measurements. The patients treated with total hip arthroplasty had reduced pain, better locomotion ability and a slight weight gain compared with the osteosynthesis group.In conclusion, a marked deterioration of nutritional and functional status was found after a hip fracture. Studies of the effect of a more powerful nutritional intervention on nutritional status and functional capacity in this group are warranted. Patients treated with total hip arthroplasty had a more favourable rehabilitation period with regard to nutritional status and locomotion ability.
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| 5. |
- Bengtsson, Per
(författare)
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In vitro studies on cholecystokinin-induced inhibition of acid formation in gastric glands
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The design of methods useful for the preparation of viable glands and cells from the gastric mucosa allowed detailed studies on the mechanisms that regulate gastric acid secretion. The preparation of rabbit gastric glands was the first suitable method to be used and a number of important scientific contributions have been accomplished with this method. Using this method we studied the effect of CCK-like peptides on [14C]aminopyrine accumulation stimulated by histamine, in order to fmd out whether such peptides can inhibit the production of acid in the parietal cell. We also developed a method for the study of viable rat gastric glands that allowed comparative studies in the rat species.In rabbit gastric glands CCK-like pep tides inhibited histamine stimulated acid formation whereas gastrin peptides were ineffective. The most potent and efficacious peptides were CCK 8 and the cholecystokinetic amphibian decapeptide cemlein reducing the maximal histamine stimulation of aminopyrine accumulation by 35-38%. The concentration of peptide necessary for eliciting inhibition was in the range of that reported to stimulate amylase secretion in similar in vitro experiments on isolated pancreatic acini, representing a well established physiological function of CCK. Analyses of somatostatin content in the incubation medium revealed that biologically active concentrations of endogenous somatostatin were released into the incubation medium. The rate of somatostatin release increased after CCK 8 or cemlein was added, whereas with G 17, the concentration of somatostatin remained unchanged. In further experiments performed with rabbit mucosal cells prepared from the gastric glands, it was demonstrated that the inhibitory property of CCK 8 only was apparent if a sufficient amount of endocrine cells were present during incubation. In highly purified fractions of parietal cells, however, a small stimulatory effect appeared, a finding that is consistent with similar capacity of gastrin and CCK stimulating the CCK2 receptors present on the parietal cell.A method useful for the study of rat gastric glands was developed. The viability of the rat gastric glands appeared excellent as judged by morphological characterisation and functional assessment by means of [14C]aminopyrine accumulation. Upon stimulation with a high dose of histamine the production of acid increased 5-fold over basal. Pentagastrin and CCK 8 were ineffective stimulators per se, but in combination with histamine a marked potentiation occurred. Somatostatin effectively inhibited histamine-stimulated acid formation both in rabbit and rat gastric glands.In conclusion, CCK-like peptides inhibit histamine stimulated acid formation in gastric glands prepared from rabbit. The inhibition is mediated in a paracrine-like mode via the release of endogenous somatostatin. A method useful for the study of viable rat gastric glands was developed. In contrast to rabbit gastric glands, CCK 8 potentiated histamine stimulation in rat glands.
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| 6. |
- Buciuto, Robert
(författare)
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Treatment of unstable trochanteric hip fractures : A clinical, mechanical and radiographic evaluation of the RAB-plate
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The problems associated with the management of proximal femoral fractures gain more attention as the elderly population continue to increase. It has been estimated that the total number of hip fractures in the world will increase from 1.7 million per year in 1990 to 6.3 million per year in 2050 (Cooper et al 1992). Operative treatment of these fractures is a challenge for the orthopaedic surgeon mainly due to poor bone quality, which increases the risk of fixation failure.More than 50% of the total number of hip fractures are extracapsular fractures. Mortality, morbidity and costs as a result of trochanteric fracture are higher than those for a cervical fracture. The consequence is increased resource consumption in the national health-care system. The estimated total cost of treatment increase 3-fold in case of a complication. Therefore, a variety of different devices have been designed in order to decrease the ratio of complications. However, in spite of this, the reported ratio of fixation failure continues be high and may reach 25% following treatment of unstable trochanteric fractures. We evaluated a new type of fixation device, the RAB-plate (Rigidity Augmentation Baixauli), for the treatment of unstable trochanteric hip fractures. The RAB-plate is a fixed 120-degree angle blade-plate with a buttress rod.We performed three clinical trials where 391 unstable trochanteric fractures were stabilised with the RAB-plate or a Sliding Hip Screw (SHS). The results showed a statistically significant lower number of complications in fractures stabilised with the RAB-plate.The fatigue resistance of the RAB-plate was evaluated in a cyclic loading test model. The RAB-plate had a statistically significant higher fatigue strength than two different designs of the SHS.Stability of the fixation and modes of failure were radiographically analysed in a series of 218 unstable trochanteric fractures treated with the RAB-plate or the SHS. The RAB-plate provided a more stable fixation especially with regard to maintained postoperative alignment. However, positive predictors for fixation failure e.g.implant position within the femoral head, varus reduction in anteroposterior projection and screw/neck angle deviation in the lateral projection were identical for both devices.Spontaneous femoral neck fracture after removal of the fixation device in healed unstable trochanteric fractures was investigated in a series of 7 patients. Our results indicate that implant-induced osteoporosis (stress protection) is a possible cause of subsequent fracture.Our conclusions are that the RAB-plate is a safe implant for fixation of unstable trochanteric hip fractures and results in lower incidence of complications compared to SHS. Therefore, the RAB can be recommended for fixation of unstable trochanteric fractures.
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| 7. |
- Cederbrant, Karin, 1964-
(författare)
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The Primary Lymphocyte Culture in the Diagnosis of Drug- and Metal-Induced Allergy
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Drugs and metals are examples of xenobiotics that can induce hypersensitivity in humans. These adverse reactions are classified as allergy if repeated exposure leads to the same type of clinical manifestation. Together with the clinical history, the skin test is the most commonly used test for the diagnosis of allergic disease. However, in vivo testing per se has drawbacks such as the risk of potentiation of the allergy or even sensitisation to a given test substance. For this reason in vitro testing is an attractive diagnostic alternative since it does not involve any exposure of the test subject to the allergen.The lymphocyte transformation test (LTT) has been used to complement the diagnosis of allergy to drugs and metals for more than thirty years. The principle behind this test is to show the presence of allergen-specific memory lymphocytes in peripheral blood, which is a sine qua non of a true allergy. LTT reveals the proliferation of such cells by showing DNA synthesis as the uptake of 3H-thymidine in primary PBMC (peripheral blood mononuclear cell) cultures treated with the allergen. However, LIT has not yet been generally accepted as a stand-alone test in the diagnosis of allergy. One reason for this is that different chemical properties of the allergens may lead to either false positive or false negative LTT responses.In the present study we investigated allergy to the drug bacampicillin and to the metals Au, Pd, Ni and Hg. Three different protocols for LTT: LIT in micro cultures (LTT-micro), LTT in macro cultures (LTT-macro) and memory lymphocyte immunostimulation assay (MELISA) were compared using a skin test or clinical history as reference methods. LTI showed a sensitivity of 87% and a specificity of 90% when used in the diagnosis of allergy to bacampicillin. When allergy to Au, Pd, Ni and Hg was investigated, the sensitivity was 33- 95% and the specificity 0-79%. There were no significant differences between the test protocols, except that MELISA showed a significantly higher specificity than LTT-micro and LTT-macro when Hg2+ was used as antigen. Even so, this specificity was only 70%, which would result in 30 of 100 healthy subjects receiving a false diagnosis of Hg allergy when using the MELISA protocol. Ni2+ also induced high numbers of false-positive LTI responses, 77-85% patch-test negative subjects showed positive results to these metals. However, group comparisons showed a significantly higher proliferation intensity in allergic than in nonallergic groups for all allergens except Hg2+. Furthermore, only 56% of patients with verified allergy to mercury showed a positive MELISA, a sensitivity that is unacceptably low.Following these findings, we investigated whether other endpoints than DNA synthesis could be used to discriminate allergic from healthy subjects, using primary PBMC cultures with Hg2+ or Ni2+ as a model system. Analysis of the T-cell receptor Vß profiles of lymphoblasts induced by these metal ions showed individual patterns, and there was no difference between healthy and allergic groups. However, the fraction of CD4+/Vß2+ cells correlated significantly with the proliferation intensity induced by Hg2+ in patients with a verified Hg allergy but not in non-allergic controls. Interestingly, such a correlation was not seen with CD8+/Nß2+ cells. This indicates that Hg2+ does not function as a superantigen, since classical superantigens also stimulate CD8+ lymphocytes. When Ni2+ was used as antigen we found significantly higher IL-10 production in allergic than in non-allergic subjects, despite no significant difference in proliferation intensity between these two groups.In conclusion, the LTT test is useful for the diagnosis of allergy to bacampicillin. Regarding Au, Pd and Ni the LIT has low validity and can only be used to discriminate groups of allergic from non-allergic individuals. LTT with Hg2+ and Ni2+ is not useful for the diagnosis of allergy to these metals since a high fraction of non-allergic individuals show positive results, irrespective of the test protocol used. This thesis calls for further studies on the usefulness of in vitro IL-10 production for the diagnosis of Ni allergy as well as on the specificity of in vitro induced CD4+N~2+ lymphoblasts from Hg allergic subjects.
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| 8. |
- Crafoord, Sven, 1950-
(författare)
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Experimental transplantation of retinal and iris pigment epithelial cells into the subretinal space
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A dysfunction of the retinal pigment epithelium (RPE) is the main cause for the development of age-related macular degeneration (ARMD) and visual loss in elderly people. For about 10 years experimental and clinical attempts to transplant RPE cells have been performed. The aims of this study were to elucidate the long term results of RPE allografts, to develop an atraumatic transplantation technique, and to explore the cellular response to RPE allografts, melanin granules, and autologous IPE cells.Surgery was performed on rabbits with a follow-up period of up to six months. After a pars plan vitrectomy, a subretinal bleb was created into which a suspension of RPE/IPE donor cells or melanin granules was injected. Pigmented RPE donor cells or preparations of melanin granules were implanted subretinally in albino rabbits. Pigmented rabbits were used in IPE transplantation. The eyes were monitored with ophthalmoscopy, fundus photography, light microscopy, electron microscopy and immunohistochemistry.Transplantation of suspensions of fresh pigmented RPE cells to the subretinal space in rabbits is feasible and induces virtually no complications when an atraumatic surgical procedure is used. The allograft forms a monolayer in conjunction with the native RPE and persists almost intact up to three months. At six months after transplantation, there was a cellular response exhibiting multilayers of cells, such as RPE and macrophages. Damage to adjacent photoreceptors in combination with melanin granules in the subretinal space indicates graft failure. No infiltration of lymphocytes was seen. Whether the cellular response was due to immunological or non-immunological mechanisms could not be determined from this experiment.Cyclosporine (CsA) could not prevent disintegration of the RPE transplant and graft failure. CsA was not capable of promoting graft survival as compared to the controls. The transplant seems to be disrupted either by immunological mechanisms that are not inhibited by CsA, or by non-immunologic events.Implantation of melanin granules to the subretinal space of albino rabbits induces a considerable phagocytic cellular response involving the host’s RPE, macrophages and glial cells. The migration of pigment-laden cells into the neural retina was frequently associated with focal photoreceptor damage. The cellular response was identical to that ensuing RPE cell transplantation. These findings support the concept that non-immunological events have a considerable influence on the outcome.In order to evaluate the impact of non-immunological mechanisms, a technique of transplanting fresh autologous IPE cells to the subretinal space of the same eye was developed. Grafted IPE cells were seen to survive for six months. There was a remodeling of the compound cellular layers in the subretinal space over time where grafted IPE cells joined the native RPE cells. The cellular response that developed exhibited macrophages, but no lymphocytes, and was in this respect similar to that observed following RPE transplantation.In RPE allografts, the photoreceptors appeared normal on light microscopy at three months, but at six months, the photoreceptors overlying the transplants generally exhibited pathological changes. In autologous IPE grafts, on the other hand, the photoreceptors displayed normal outer segment length and outer nuclear layer on top of grafted IPE cells. Focally, multilayers of both grafted IPE and RPE cells, together with macrophages, induce damage to adjacent photoreceptors as observed at 6 months. Cellular multilayers in the subretinal space, irrespective of genesis, are likely to have adverse effects on photoreceptors. The experiments using autologous IPE grafts show that non-immunogenic mechanisms have a decisive impact on the outcome of the transplant in the subretinal space.
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| 9. |
- Dahlfors, Gunilla
(författare)
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Action and interaction of growth factors and regulatory molecules in vascular cells : With special reference to the IGF-I-system
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vascular function is greatly influenced by growth factors and regulatory molecules that can interact with each other in a complex pattern in the vascular wall. In this thesis we studied how different substances of special interest in the pathogenesis of vascular disease interact and regulate each other's expressions in endothelial cells and vascular smooth muscle cells (VSMCs).In VSMCs, angiotensin II was shown to delay PDGF-BB induced cell growth. This transient inhibitory effect of angiotensin II was mediated by the AT1-receptor, did not involve autocrine action of transforming growth factor-ß1 (TGF-ß1) and acted at a site downstream of PDGF-ß receptor phosphorylation.The interaction of the insulin-like growth factor-system (IGF-system) with various growth factors, glucose and nitric oxide (NO) was studied in vascular cells. Vascular endothelial growth factor (VEGF) and transforming growth factor-ß1 (TGF-ß1) regulated the expression of insulin-like growth factor-binding proteins (IGFBPs) in large vessel endothelial cells in a way that might cause an increased bioavailability of IGF-I locally in the subendothelial space. Angiotensin II, IGF-I and insulin did not affect IGFBP expression in these cells. The expression of IGFBPs was studied for the first time in human micro vessel endothelial cells. No effect of high glucose treatment on IGFBP expression was seen in either large vessel endothelial cells or microvessel endothelial cells. A possible interaction between NO and the IGF-system was studied in VSMCs. IGF-I did not have any significant effect on NO production in VSMCs and neither exogenous nor endogenous NO had any effect on IGFBP expression.In conclusion, we found that angiotensin II interacts with PDGF-BB in the regulation of VSMC growth. The IGF-system is regulated by VEGF and TGF-ß1 in endothelial cells while no effect of angiotensin II, IGF-I, insulin or high glucose was seen. We found no evidence for interaction of NO and the IGF-system in VSMCs.
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| 10. |
- Ekbäck, Gustav
(författare)
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Perioperative blood saving techniques with coagulative evaluation in orthopedic surgery
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Allogeneic blood transfusion, although often needed in major surgery with large per-and postoperative bleeding, is fraught with dangers such as clerical mishandling, immunosuppression and blood-borne infections. It is therefore important to find ways to avoid allogeneic blood transfusion by means of less bleeding, better tolerance of the bleeding or alternatives to allogeneic blood.Aim of the study: To evaluate different methods of blood saving in total hip replacement (THR) surgery, their efficacy, and the possible risks, especially hyper- and hypocoagulation.Patients and methods: A total of 179 patients and eight volunteers were included in five studies. All patients were operated by primary TI-IR. Blood loss, allogeneic transfusions, coagulation parameters (platelets, bleeding time, fibrinogen, APTT, PT, soluble fibrin, TAT), fibrinolysis parameters (D-dimer, tPA, PAT, PAP), functional coagulation analysis (Sonoclot, TEG) and frequency of deep vein thrombosis (ultrasonography) were investigated according to the different study regimes. Thitiy patients undergoing predonation of autologous blood (PAD) with or without autotransfusion were compared with a control group of 15 patients without blood saving treatment. Fatty patients undergoing immediate prcopcrative platelet rich plasma (PRP) harvest and autotransfusion were compared with 40 patients undergoing PAD and autotransfusion. The spontaneous and induced activation of the platelets in the blood of20 patients undergoing THR with or without additive PRP harvest were also studied with flow cytometry. The efficacy of tranexamic acid (TA) as a blood saving method was examined in a study including 40 patients. As Sonoclot coagulation analysis was the single most important coagulation analysis during the studies, a methodological examination including eight volunteers was done for the instrument.Results and discussion: If no blood saving method is used there is a very strong possibility of allogeneic blood transfusion (100% of the patients studied needed blood). Autotransfusion is not sutlicient as a single transfusion reducing method (53% patients studied still needed blood). PAD+ autotransfusion gives sufficient reduction in allogeneic blood transfusion (5-27% of patients in tlte different studies needed blood) but needs prcopcrativc planning, and PAD is not accepted by Jehovah's Witnesses. PRP reduces allogeneic blood transfusion as effectively as predonation of two units of blood (15% of studied patients needed blood) and can replace PAD in unplanned operations and for Jehovah's Witnesses. The majority of platelets are in a resting state during THR and PRP harvest. PRP harvest did not affect the degree of platelet activation, but there were great individual differences between patients (spontaneous activated platelets, i.e. presenting P-Selektin during the operation, between 1 %-23%). Most of the platelets in the c-PRP were not activated at the time ofretransfusion but were easily activated upon stimulation with the physiological activator ADP. TA therapy started prcoperatively is easily performed and reduces bleeding by 35%, probably by significantly reducing induced fibrinolysis perioperatively. During primary THR surgety there was an early postoperative hypocoagulation during the first postoperative day, with a hypercoagulation later postoperativcly, and an observed maximal value about 7 to 10 days postopcrativcly that was still evident three weeks postopcratively. Per- and early postoperatively there was also a marked fibrinolysis that was normalized on day 1 postoperatively. Six of the 120 patients examined with ultrasonography had DVTs, all after the first week postoperatively. There were no differences in the frequency of detected DVTs, irrespective oftrcahnent with PAD, PRP or TA. Sonoclot coagulation analysis was found to be a valuable tool in detecting hypercoagulability but was restricted by a high variability. This variability can be lowered by a dual machine setting, repetitive analysis and directly analyzed arterial samples.Conclusion: The combination ofperioperative autotransfusion and PAD is effective in preventing allogeneic blood transfusions during primary THR. PRP harvest is as effective as PAD and is useful for patients who cannot donate blood. A minor propotiion of the patient's platelets are activated during the surgery irrespective of whether or not there is PRP harvest. TA therapy started preoperatively reduces fibrinolysis during the day of surgery and reduces per-and postoperative bleeding by 35%. Primmy THR surgery gives rise to an initial hypocoagulation followed by a hypercoagulation with an observed maximal value about 7 to 10 days postoperatively which is still evident three weeks postoperatively. However, the observed frequency of thrombosis was low (5%) in the 120 patients examined with utrasonography. Sonoclot analysis is an efficient tool for following this hypercoagulation. The high variability of the method can be reduced with a dual machine setting, repetitive analysis and directly analyzed arterial samples.
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