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  • Adolfsson, Lars, 1955- (författare)
  • Arthroscopy in the upper extremity
  • 1992
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>This stndy comprising six separate papers, is concerned with the techniques of, and bevaluation of arthroscopy as a diagnostic and therapeutic tool in different pathologic conditions in the upper extremity.</p><p>Arthroscopy proved to increase diagnostic accuracy in 177 examined patients with anterior shoulder instability or shoulder pain. Previously not well described patterns of pathological morphology in the ventral joint capsule after anterior shoulder dislocations were disclosed. A new classification system of rotator cuff pathology to be used for arthroscopy in the subacromial impingement syndrome is suggested. Different stages of rotator cuff pathology were found to influence the clinical results after arthroscopic acromioplasty in 79 patients.</p><p>An anatomical stndy on 16 cadaver elbows revealed the close proximity between commonly used arthroscopic portals and important neurovascular structures. The usefulness and potential risks of each portal were demonstrated and a preferred procedure for diagnostic elbow arthroscopy was suggested.</p><p>Wrist arthroscopy was performed in 30 patients with long-standing post-traumatic pain and resulted in increased diagnostic accuracy. In patients where clinical examination and radiography had shown no abnormality, arthroscopy demonstrated serious carpal ligament injuries and related instability.</p><p>A technique for arthroscopic wrist synovectomy was described in patients with rheumatoid arthritis. In 18 wrists of 16 patients, a reasonably radical synovectomy could be achieved with this atraumatic method. Primary results showed decreased pain and increased grip-strength in all patients and an increased range of motion in some.</p>
  • Afoke, Anthony Okoro (författare)
  • Some epidemiological aspects of insulin-dependent diabetes mellitus in Nigeria and Sweden
  • 1993
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>In the western world diabetes mellitus is one of the most common severe diseases in childhood, but it is rarely seen in black African populations. However, there are very few epidemiological studies of childhood diabetes in Africa and almost nothing is known of the Nigerian population. One aim of this study was therefore to estimate the prevalence of insulin dependent diabetes (IDDM) in children and adolescents and to characterize their type of diabetes.</p><p>A screening of almost 78,000 school children was performed and beside some already known diabetic patients several new cases were diagnosed. It was found that IDDM is much less common than in Europe but on the other hand more common than in several Asian countries. In addition the prevalence found may be underestimated because of cultural and social factors, health care problems and high mortality in diabetes. Although most patients had a clinical picture of Malnutrition Related Diabetes (MRD) we found in some cases autoantibodies towards islet cells and insulin and furthermore the same HLA-DQ-type-associations as seen to Type 1 diabetes in caucasian diabetics.</p><p>While we saw no seasonal variation of diagnosis of Nigerian IDDM, there is a pronounced such seasonal variation in Sweden. This study has tried to elucidate whether this seasonal variation is related to any differences in manifestation and clinical course. Patients diagnosed during incidence peaks had more often short duration of symptoms before diagnosis,ketonuria at diagnosis, rapid loss of endogenous insulin secretion but increase of insulin antibodies and of glycosylated haemoglobin. They had also more often infections before diagnosis and high serum immunoglobulins (IgG and IgM) up to 9 months after diagnosis. HLA-DR4 was more common in these patients. The results suggest that IDDM in Swedish children is heterogenous.</p>
  • Andersson, A. Christer (författare)
  • Acute anterior cruciate ligament injuries : evaluation of surgical och non-surgical treatment
  • 1991
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>This study comprising 6 separate papers is concerned with the treatment of patients with acute anterior cruciate ligament (ACL) injury. The aim was to compare primary surgical and non-surgical ACL treatment. Treatment was, therefore, instituted at random in all consecutive patients (n = 293) with ACL injury.</p><p>Initially all patients were investigated by arthroscopy and examined under anesthesia.</p><p>After 4 years patients treated by ACL repair with combined intraarticular and extraarticular augmentation had a better stability, fewer knee symptoms and a higher level of activity than patients treated by nonaugmented ACL repair or by repair of the associated injuries alone. The patients in the latter group commonly developed instability symptoms and ACL reconstruction was required in 20"7o ofthem. Also they frequently had subsequent meniscal injuries, and an impaired knee function at one-leg-hop tests for distance. Running tests, however, was not correlated to ACL treatment.</p><p>Another group of patients with acute ACL injury did not have any primary ligamentous repair. At one year 200Jo of the patients needed reconstructive surgery. Moreover, anteriorposterior laxity at one year was increased compared to the initial measurements. The greatest initial laxity was found in patients with an associated tear of the medial collateral ligament (MCL). The patients with combined ACL and MCL injuries had the worst prognosis.</p><p>In patients with combined injuries who had primary repair of grade 2-3 MCL tears the outcome was similar as for patients with isolated ACL lesion.</p><p>A simple device for static measurements of anterior-posterior knee displacement was valuable for evaluating the results of ACL treatment. lt can also be used as an aid in the diagnosis of acute knee injury.</p>
  • Arnesson, Lars-Gunnar, 1947- (författare)
  • Small breast cancers : Diagnosis, prognostic factors and clinical outcome in a screening population
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Breast cancer ≤ 10 mm together with ductal in situ cancer of the breast (DCIS) today constitute more than 40% of screening detected breast malignancies. Prognostic factors, diagnosis and clinical outcome for invasive breast cancers ≤ 10 mm and local recurrence in DCIS were evaluated.</p><p><strong>Histopathological grading</strong> was done in 248 ductal breast cancers and grade III was correlated to aneuploidy, increased S-phase fraction and receptor negative tumours. Life table analysis showed a significant increase in breast cancer mortality in grade III tumours (p &lt; 0.001).</p><p><strong>Hormone receptors and cytometric variables</strong> were studied in ≤ 10 mm breast cancers. Around 60% of these small cancers were evaluable. Aneuploidy was found in 52% and SPF ≥ 10 in 20%. Mean SPF was 4.8 in diploid and 7.6 in aneuploid tumours. A potentially high risk group with high SPF figures and receptor negative tumours comprise 7% of the patients.</p><p><strong>Diagnostic surgery</strong> was performed in 314 non-palpable breast lesions. Insufficient excisions were observed in 16 cases (5%), mostly in lesions with microcalcifications and in situ cancers ≥ 30 mm in extent. Underestimation of in situ cancers is the main reason for inadequate surgery.</p><p><strong>DCIS</strong> comprises approx 10% of breast malignancies. In 38 cases operated with breast preserving surgery 13% got local recurrence in median 60 months follow-up.</p><p><strong>Recurrence free survival</strong> in patients with ≤ 10 mm breast cancers were evaluated for 324 cases. Only 8% of these patients had adjuvant treatment. Lymph node involvement was found in 9% of screening detected and 20% in clinically detected cancers (p &lt; 0.03). Median prospective follow-up time was 7 years and distant metastases appeared in 8 patients, local recurrence in 3. Life table analysis showed 97% overall distant recurrence free survival, 99% in node negative and 79% in node positive patients (p &lt; 0.001).</p><p>We can today, by grading and cytometric variables, find subgroups with high risk of recurrence after breast cancer surgery in small breast cancers. These are probably the only patients that benefit from adjuvant treatment and need follow-up outside mammography screening. Breast conserving surgery can be performed in the majority of DCIS patients.</p>
  • Arranz, Belén (författare)
  • Neurobiological aspects of human aging and suicide
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>This thesis addresses: 1) The involvement of the monoaminergic and neuropeptidergic neurotransmitter systems in the aging process, and 2) The contribution of these systems in the etiology of an age-related mental disorder: the depressive syndrome. Because of the evidence suggesting the efficacy of the SSRI in the treatment of some age-related symptoms, a comparison study of the binding characteristics of two SSRI, i.e. [3H]paroxetine and [3H]citalopram, to the human brain 5-HT uptake site was included.</p><p>Neurochemical analysis, involving HPLC, binding assays and RIA methods, was performed in several brain regions from 23 control subjects and 18 suicides pooled according to the method of death and the prior existence of depressive symptoms.</p><p>Both [3H]paroxetine and [3H]citalopram were found to label the same number of presynaptic 5-HT binding sites, which is in accordance to their ability to identify the same membrane protein. However, the 15 to 30-fold higher affinity displayed by [3H]paroxetine gives evidence to this SSRI having a more easily accesible binding domain in the 5-HT transport complex than [3H]citalopram, and hence being a better marker of thispresynaptic 5-HT carrier system.</p><p>No statistical differences in either the monoamines 5-HT, NA and DA, their metabolites or the 5-HT binding sites were found between controls and overall suicides. However, a diminished number of 5-HTl D binding sites with advancing age, together with a significant decrease in the number of 5-HTl D binding sites and binding affinity was noticed in the nondepressed and depressed suicides, respectively. These results might indicate the involvement of this novel 5-HT receptor in both some of the physical disturbances present in the elderly population and in the mechanisms underlying the depressive syndrome. Advancing age was also found to be negatively correlated with brain NA, DA and HV A concentrations, thus supporting the increased likelihood of changes in feeding habits and in the hypothalamic-mediated endocrine dysfunctionscommonly observed in senescence.</p><p>With regard to the neuropeptidergic neurotransmitter systems, age-related decreases in gyrus cinguli NPY and CRF concentrations were noted. In addition, although unchanged NPY, SOM and CRF concentrations were observed in the overall suicide group, the HPLC analysis revealed that the depressed suicides showed a different pattern of NPY-LI fragments, which is in agreement with depression being associated with an altered processing or metabolism of the intact NPY molecule.</p>
  • Bendtsen, Preben, 1956- (författare)
  • Rheumatoid arthritis - patient perception of disease, care, quality of life, coping and well-being : a study from a Swedish health care district
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>During the past decades, the focus of outcome studies in chronic diseases such as rheumatoid arthritis (RA) has changed from a technical and biological preoccupation towards a more patient-concemed psychosocial perspective. The changing paradigm of chronic disease impact has been conceptualised in a number of self-report health status and outcome measurements that have been called 11one of the primary achievements of rheumatology in the 1980s". The overall aim of the study was to make a broad elucidation of the perceived selfMreported impact of rheumatoid arthritis in a representative group of individuals from a health care district, with regard to treatment and care, quality oflife, coping and well-being.</p><p>A total of 321 patients from a health care district in the northern part of Kalmar county, Sweden, with both early/mild and more severe disease were enrolled in the first part of the study, in which the medical records of these individuals were scrutinised for information about previous treatment and care. In the second part of the study, 222 of the initial 321 persons participated in an extensive postal survey exploring perceived impact of RA by self-report.</p><p>The uncertain outcome of RA disease was emphasised by a high frequency of discontinuations of drug therapy due to lack of effect or side-effects. Underlining the lack of a medical cure for RA, more than 40% of the individuals had undergone some kind of surgical procedure due to the disease. The rehabilitation services to individuals with RA appear to be functioning fairly adequately since those still working were employed in administrative work rather than in production. The participants indicated a preference for a good reception by health care workers rather than technically correct care. Only a minority of the patients who had been treated as in-patients felt that they had been involved in the planning of the care. Also, the physicians seemed to underestimate the patients desire for information concerning both medical and social aspects of the disease.</p><p>Quality of life scores exhibited a change for the worse with increasing self-reported functional disability. Physical, psychological and social life domains were fairly highly interrelated and all revealed lower levels with increasing self-reported functional disability. Also, lower levels of well-being were closely associated with a more severe RA disease, in particular loneliness, indolence, tension, security, future-orientation and endurance. Coping and wellMbeing were only weakly interrelated, but individuals who declared an active lifostyle exhibited a better well-being with a higher basic mood, greater fotureorientation and less indolence, loneliness and inferiority. Individuals accepting the RA disease displayed less guilt and tension, and greater endurance and basic mood.</p><p>The study depicts how individuals with RA in a health care district are provided with both the basic treatment and more specialised care in a collaboration between medical and surgical specialists. In general, satisfaction with the care provided was more closely related with clinical signs rather than self-reported functional performance, although the latter might more adequately reflect the perceived need of the patients. Thus, the results support the application of self-reported functional disability assessment in routine clinical rheumatological practice. The study displays methods that measure and quantify the increasing negative psychosocial impact of RA with increasing functional disability. Some evidence was also found supporting the inclusion of coping enhancement elements in health care programmes targeting patients with RA. Consequently, the inclusion of counselling enhancing acceptance of the RA and encouraging decisions about new relevant goals might, at least theoretically, increase well-being in patients with RA.</p>
  • Bengtsson, Bengt-O (författare)
  • On the hypersensitivity syndrome induced by the selective serotonin reuptake inhibiting antidepressant Zimeldine : A clinical and experimental study
  • 1992
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Zimeldine, the first selective neuronal serotonin (5-H1) reuptake inhibitor to be registered as an antidepressant was withdrawn from common use due to an acute flu-like adverse syndrome comprising fever, myalgia and/or arthralgia and signs of disturbed liver function. A few of these patients also developed a peripheral neuropathy, in the most serious form a Guillain-Barré syndrome (GBS). The reaction was tentatively termed a hypersensitivity syndrome (HSS).</p><p>Patients who had developed a HSS during zimeldine therapy (HSS-patients) were compared to control patients who tolerated the drug.</p><p>No predictor to the HSS emerged concerning demographic data, psychiatric illness, previous medical history, medications with zimeldine or other drugs, other diseases, professional or nutritional circumstances. Nor was there any sign that HSS-patients who also developed neurological symptoms had a different profile of the HSS than other HSS-patients. Earlier zin1eldine treatment per se was not seen to predispose for development of a HSS or any other kind of adverse experience during subsequent therapy. The spectrum of adverse reactions was in agreement with those reported in previous studies and no new case of the GBS was revealed. The estimated frequency of HSS ranged from 0.63 to 3.4 % in spontaneous reports to the regnlatory authority and 1.4- 13% in a written inquiry. Among closely monitored inpatients 31 %developed a HSS. The mechanism for the HSS does not seem to be related primarily to the 5-HT reuptake inhibition as such. No HLA-associated disposition for the HSS was found. Nor was there any support for a HLA-associated disposition for depressive disorders. The pathogenetic mechanism for the HSS seems to involve an inlmunological response to antigens related to zimeldine.</p><p>Zimeldine and its main primary metabolite norzimeldine both suppressed clinical signs of experimental allergic neuritis (EAN) in Lewis rats. Imrnunomodulatory effects in vitro of zimeldine, its metabolites norzimeldine and CPP 200 as well as of other monoamine reuptake inhibiting antidepressants were identified in the same EAN model.</p><p>These observations call for further research on immunological mechanisms in the pathogenesis of mental disorders as well as on the potential role of drugs acting on the monoamine systems in the treatment of autoimmune diseases. The findings also justify a discussion on the application of immunological methods in the testing of new psychopharmacological drugs.</p><p>Based on the presented results the tentatively used term for the adverse reactions to zimeldine, the hypersensitivity syndrome, seems justified.</p>
  • Berg, Sören, 1954- (författare)
  • Hyaluronan in sepsis : A clinical and experimental study
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Sepsis and septic shock are important causes of morbidity and mortality in the intensive care unit (ICU). Mortality rates in septic shock are estimated to be 40-50%, in spite of modem intensive care. Death is commonly caused by cardiovascular collapse and multiple organ dysfunction syndrome (MODS). Hepatic dysfunction is a common component of MODS, and can have a major impact on prognosis and survival. Sepsis is, among other derangements, also accompanied by disturbed tissue water homeostasis with increased extravasation of water resulting in tissue edema.</p><p>Hyaluronan is an interstitial macromolecule that participates in the regulation of tissue hydration. It is normally present in small concentrations in the blood, and is rapidly cleared from the blood by the liver endothelial cells. The synthesis of hyaluronan can be stimulated by inflammatory mediators. Thus sepsis and hyaluronan turnover could interact in many ways. The aim of the present investigations was to study possible changes in circulating hyaluronan concentrations in relation to sepsis and septic shock.</p><p>Plasma levels of hyaluronan were studied in 44 patients with infections and septic shock. Increased plasma concentrations were found, and the increase correlated to disease severity and outcome. In experimentally induced sepsis in pigs, an increase in circulating concentrations was found, and a relation to hemodynamic instability and outcome was seen. A moderate increase in blood hyaluronan concentrations was seen after surgical trauma in both humans and pigs. Crystalloid infusion therapy also caused a small increase in plasma hyaluronan concentrations in healthy volunteers, probably through an increased washout of interstitial hyaluronan. The hepatic turnover of hyaluronan was studied in septic shock patients. Low extraction ratios at high circulating concentrations were found, suggesting a reduced capacity of hepatic uptake and an increased inflow to the circulation. The kinetics of plasma turnover of hyaluronan were studied in septic and non-septic ICU patients. A prolonged half-life was seen among the septic patients, suggesting a reduced clearance capacity.</p><p>In conclusion, sepsis is accompanied by increased circulating hyaluronan concentrations. The magnitude of the increase seems to correlate to disease severity and outcome. The cause of this increase is suggested to be both reduced hepatic uptake function, and increased input to the circulation. The relative contributions of these mechanisms, and the possible clinical utility of plasma hyaluronan measurements, remain to be determined.</p>
  • Blomberg, Björn, 1948- (författare)
  • Helicobacter pylori : Prevalence, heterogeneity, and ulcerogenic properties
  • 1993
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>In 117. unselected patients <em>H. pylori</em> infection was found in 49.6% by combining culture and acndme orange stammg of hssue sections. Infection was equally common in the gastric body and antrum. The activity of gastritis was generally higher in the antrum. The overallagreement between acridine orange stain and culture was 0.93.</p><p>Formalin treated <em>H. pylori</em> whole cells were used to immunize rabbits. With the aid of coagglutination and indirect immunofluorescence all <em>H. pylori</em> strains tested were shown to contain cross reactive antigens, but no serum cross-reacted with all strains tested. Multiple, antigenically different, isolates were found in some patients and a provisional serogrouping based on heat-stable antigens was proposed.</p><p>Acid glycine extracts from four H. pylori strains were prepared. Rabbit antisera against these, and ten further, strains showed extensive cross-reactions with all four extracts. An EIA based on <em>H. pylori</em> strain NCTC 11637 had a sensitivity of 90 % and a specificity of 87 %.</p><p>In 197 unselected patient culture, histopathology using acridine orange or Giemsa staining, and serology was evaluated. 33.5 % of patients were infected by <em>H. pylori</em>. The sensitivities for culture/acridine orange stain/Giemsa stain were 0.94/0.86/0.91 respectively. The specificities were 1.0/1.0/0.84. For two commercial serologic tests the negative predictive values were 0.93/0.95 respectively. A strategy of serologic screening to avoidunnecessary endoscopies was suggested, but that positive serology be confirmed by histopathology.</p><p>Sixty-one human gastric isolates of <em>H. pylori</em> were tested for their ability to induce oxidative burst in human neutrophils. A cell bound, heat-labile, property able to induce a strong and rapid oxidative burst in neutrophils in the abscence of opsonins, was found in about one third of strains tested. This property was significantly associated with peptic ulcer disease(p=0.0261, Fisher's exact test).</p><p>Fifty-four clinical isolates of <em>H. pylori</em> were tested for cytotoxin production and their ability to induce oxidative burst in human neutrophils. Nonopsonised, 20 strains showed a rapid and strong oxidative burst, 30 a slow and weak response, and four remaining gave inconclusive results. Cytotoxin production was seen in 10 of 20 rapid and strong inducers, but only in 3 of 30 with a slow and weak response (p=0.0027, Fisher's exact test). 11/15 of the cytotoxin producing strains (p=0.0135) and 13/20 of the rapid and strong inducers (p=0.0209) were from 22 patients with peptic ulcer disease. The ability of some nonopsonised <em>H. pylori</em> to activate neutrophils showed eo-variation with cytotoxin production, but the two properties seem to be independent markers of peptic ulcer disease.</p><p>With theuse of electron microscopy the interactions of human neutrophils with four nonopsonised <em>H. pylori</em> strains, two rapid and strong, two slow and weak inducers of neutrophil oxidative burst were studied in morphologic detail. The rapid inducers were phagocytosed within minutes, whereas the slow inducers showed little reaction even after one hour.</p><p><strong>Conclusions</strong>: Histopathology using acridine orange or Giernsa stains correlates well with culture. Serologic screening might be of value to reduce unnecessary endoscopies. A cellbound heat-labile property of some <em>H. pylori</em> strains able to nonopsonised induce a rapid oxidative burst in neutrophils is significantly associated with peptic ulcer disease. This property is also associated with, but independent of, cytotoxin production.</p>
  • Bornfeldt, Karin E. (författare)
  • Actions and interactions of insulin-like growth factor-I and insulin in vascular smooth muscle
  • 1991
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Insulin-like growth factor-I (IGF-I) is a polypeptide with structural and biological similarities with insulin, and the receptors for IGF-I and insulin are homologous. The present investigation was devoted to the actions and interactions of IGF-I and insulin in vascular smooth muscle.</p> <p>In vascular smooth muscle from intact arteries and in cultured vascular smooth muscle cells there are abundant IGF-I receptors, but very few insulin receptors. IGF-I and insulin stimulated proliferation of cultured vascular smooth muscle cells, and the effects were probably mediated via the IGF-I receptor. However, the maximal growthpromoting effect of IGF-I was twice the maximal effect of insulin. If an acidic amino acid was substituted for the basic amino acid histidine in insulin B-chain (BlO His:::} Asp), like in IGF-I, the maximal growth-promoting activity reached the effect of IGF-1. The amino acid in position 10 in insulin B-chain may thus be important for the growthpromoting activity of insulin.</p> <p>Vascular smooth muscle cells express IGF-1 mRNA and produce imm1,1noreactive IGF-1 in vitro. Levels of IGF-1 m RNA were decreased by platelet-derived growth factor (PDGF-BB), basic fibroblast growth factor (bFGF) and serum, whereas IGF-1 and high concentrations of insulin increased IGF-I rnRNA and immunoreactive IGF-I. It is thus possible that IGF-1 is able to increase its own production in an autocrine loop withpositive feedback. The growth-promoting effects of IGF-1 and insulin were weak compared to the effects ofPDGF-BB and bFGF. The results indicate qualitative as well as quantitative differences between IGF-1 and insulin compared to PDGF-BB and bFGF.</p> <p>IGF-1 gene expression in aortic tissue was found to be decreased by diabetes and fasting in vivo, and the levels were restored if diabetic rats were treated with insulin.</p> <p>Vascular smooth muscle proliferation induced by balloon catheterization was found to be impaired by diabetes and increased by insulin-treatment in vivo, although not to the levels in normal rats. IGF-1 stimulated vascular smooth muscle proliferation in diabetic rats in vivo without affecting the diabetic state, and IGF-I gene expression was increased in proliferating vascular smooth muscle. The results suggest that IGF-I is involved in vascular smooth muscle proliferation in vivo.</p> <p>In conclusion, insulin is less potent than IGF-1 in stimulating proliferation of vascular smooth muscle, and the growth-promoting effects of insulin are weaker than the effects ofiGF-1, suggesting that insulin in concentrations found in plasma has little direct effect on vascular smooth muscle proliferation. IGF-1 is probably of importance for vascular smooth muscle proliferation, and the results suggest that IGF-1 can be locally produced and regulated in the vascular wall.</p>
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