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  • Johansson, Magnus, 1973- (författare)
  • On noise and hearing loss Prevalence and reference data
  • 2003
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Noise exposure is one of the most prevalent causes of irreversible occupational disease in Sweden and in many other countries. In hearing conservation programs, aimed at preventing noise-induced hearing loss, audiometry is an important instrument to highlight the risks and to assess the effectiveness of the program. A hazardous working environment and persons affected by it can be identified by monitoring the hearing thresholds of individual employees or groups of employees over time. However, in order to evaluate the prevalence of occupational noise-induced hearing loss, relevant reference data of unexposed subjects is needed.The first part of this dissertation concerns the changes in hearing thresholds over three decades in two occupational environments with high noise levels in the province of Östergötland, Sweden: the mechanical and the wood processing industries. The results show a positive trend, with improving median hearing thresholds from the 1970s into the 1990s. However, the hearing loss present also in the best period, during the 1990s, was probably greater than if the occupational noise exposure had not occurred. This study made clear the need for a valid reference data base, representing the statistical distribution of hearing threshold levels in a population not exposed to occupational noise but otherwise comparable to the group under study.In the second part of the dissertation, reference data for hearing threshold levels in women and men aged from 20 to 79 years are presented, based on measurements of 603 randomly selected individuals in Östergötland. A mathematical model is introduced, based on the hyperbolic tangent function, describing the hearing threshold levels as functions of age. The results show an age-related gender difference, with poorer hearing for men in age groups above 50 years.The prevalence of different degree of hearing loss and tinnitus is described for the same population in the third part of the dissertation. The overall prevalence of mild, moderate, severe or profound hearing loss was 20.9% collectively for women and 25.0% collectively for men. Tinnitus was reported by 8.9% of the women and 17.6% of the men. Approximately 2.4% of the subjects under study had been provided with hearing aids. However, about 7.7% were estimated to potentially benefit from hearing aids as estimated from their degree of hearing loss.Noise-induced hearing loss primarily causes damage to the outer hair cells of the inner ear. The fourth and last part of the dissertation evaluates the outer hair cell function, using otoacoustic emission measurements (OAE). Prevalence results from three different measuring techniques are presented: spontaneous otoacoustic emissions (SOAE), transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE). Gender and age effects on the recorded emission levels were also investigated. Women showed higher emission levels compared to men and for both women and men the emission levels decreased with increasing age. The results from the OAE recordings were shown to be somewhat affected by the state of the middle ear. The study included tympanometry, and the relation of the outcome ofthis test to the otoacoustic emissions is described, where high middle ear compliance resulted in low emission level. Reference data for the tympanometric measurements are also presented.The results of this project form an essential part of the important work against noiseinduced hearing loss, which needs continuous monitoring. The reference data presented here will provide a valid and reliable data base for the future assessment of hearing tests performed by occupational health centres in Sweden. This data base will in turn prove useful for comparison studies for Sweden as a responsible fellow EU member country setting high standards for work force safety. The statistical distribution of hearing threshold levels as a function of age for men and women in tabulated form is available on the Swedish Work Environment Authority (Arbetsmiljöverket) web site: http://www.av.se/publikationer/bocker/fysiskt/h293.shtm.
  • Aardal-Eriksson, Elisabeth (författare)
  • Salivary cortisol and posttraumatic stress reactions : methodological and applied studies before and after trauma
  • 2002
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The field of psychotraumatology has its roots in ancient history. During the past decades, the surveillance of the psychobiological background of reactions to and consequences of traumatic stress has made great progress and the complexity of the human stress response system stands out. The hypothalamic-pituitary-adrenocortical axis activity, modulated by various neuroimmunological substances, seems to play a major role in the stress response. However, there are still inconsistencies in explanations of relationships between biological and psychological changes following traumatic stress. Moreover, the matter of predictive factors for the development of posttraumatic morbidity is still in a speculative phase.The aims of the present thesis were to further develop a commercial serum cortisol radioimmunoassay (RIA) for determination of cortisol in saliva and to test its reliability, specificity and sensitivity as a biochemical assay. The saliva sampling procedures and sample storage stability were also to be tested. Further issues were to investigate determinations of salivary cortisol and serum prolactin in relation to selfratings of posttraumatic psychological distress and general psychological health. Possible predictive and concurrent validity of salivary cortisol as a biochemical marker for posttraumatic psychological distress were to be tested.Cortisol is present in saliva mainly in non-protein form, representing the free, biologically active fraction of the total plasma cortisol concentration. In a first phase of the present thesis, the commercial serum cortisol RIA was modified for determination of cortisol in saliva. The relation between salivary and serum cortisol concentrations was tested. Reference ranges at 8 AM and 10 PM for the salivary cortisol assay were established from 195 healthy subjects. Salivary cortisol concentrations were tested in relation to serum cortisol in estimating adrenocortical function during endocrine dynamic function tests in 37 patients and 13 healthy controls. In testing salivary cortisol as a marker for stress for fieldwork use, a screening study was performed on 66 male rescue workers. Salivary cortisol at 8 AM and 10 PM and serum prolactin were determined and general psychological health and posttraumatic psychological distress were estimated with the self-rating scales General Health Questionnaire, Impact of Event Scale and Posttraumatic Symptom Scale. These scales were used in the second phase of the thesis. Three applied follow-up studies were performed with sampling of salivary cortisol and self-ratings: (a) a study of 31 UN-soldiers five days, two and nine months after a mine accident; (b) a study of 145 UN-soldiers before, at return, and two and six month after a six month mission. (c) a study of 101 UN-soldiers six and twelve months after a six month mission with severe combat exposure.The results from the present thesis indicate that the modified method of salivary cortisol determination possesses sufficient precision, accuracy, sample storage stability and procedural advantages for laboratory, clinical and field application. Moreover, it possesses moderate predictive information and moderate to high concurrent validity as a biochemical marker for posttraumatic psychological distress.
  • Adell, Gunnar, 1953- (författare)
  • Indicators of colorectal cancer prognosis and response to preoperative radiotherapy
  • 2000
  • Doktorsavhandling (övrigt vetenskapligt)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.
  • Adolfsson, Per, 1967- (författare)
  • Regulatory importance of cyclic nucleotides in smooth muscle growth of the urogenital tract
  • 2001
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Smooth muscle hyperplasia/hypertrophy is, if not responsible for, so at least involved in those diseases, which impair life quality for most people in today's society.This thesis, presents a pharmacological investigation, related to the regulatory role of cyclic nucleotides, of smooth muscle hyperplasia/hypeitrophy in human uterine leiomyoma and benign prostate hyperplasia (BPH).Four main aspects, with cAMP as a connecting thought, have been analyzed, namely expression and characterization of the adrenergic receptors (AR), determination of adenylyl cyclase (AC)- and phosphodiesterase (PDE)-activity, and finally the connection between mentioned issues and proliferation of cultured smooth muscle cells (smc).In the frrst paper, characterization of the a 2-adrenergic receptor (az-AR) subtypes in human myometrium at term pregnancy was examined by combining radioligand binding-studies with reverse transcriptase-polymerase chain reaction (RT-PCR). Results demonstrated a significant eo-expression of α2A and α2B, and a weak indication of the α2C-AR, which however was identified at the mRNA level by the RT-PCR analysis.In the next investigatio~ smooth muscle tissue of human uterine leiomyoma (benign smooth muscle tumor) was compared with surrounding myometrial tissue (control). The expression of AR, AC- and PDE-activity was analyzed, as well as the effect of cAMP with respect to growth regulation of cultured leiomyoma smc. Primarily, a significantly reduced ß2-AR expression and AC-activity was detected in leiomyoma compared to control tissue, whereas the PDE-activity was approximately 100% higher. In addition, the α2-AR population in leiomyoma was slightly increased. When cultured leiomyoma smc was treated with cAMP increasing agents as forskolin, an AC stimulating agent, or papaverin, a general PDE inhibitor, a considerable inhibition of DNA replication and protein synthesis was obtained.In the thh·d paper, a proliferation study was made on cultured benign prostate hyperplasia smc, were the mitogen effect of lysophosphatidic acid (LPA) and cAMP/cGMP increasing agents was investigated. LPA generated a dose-dependent mitogen response, which was efficiently inhibited, both by forskolin, and by papaverin. In addition, sildenafil (Viagra®), which serve as a potent and selective PDE5 inhibitor, also decreased the LPA mediated growth promotion in a dose dependent manner.The last study, demonstrate primarily the expression pattem of LPA receptors (Edg) in BPH smc. Further, the intracellular cAMP changes in LPA stimulated BPH smc and the proliferative effect of the LPA analogue sphingosine 1-phosphate (SIP) was considered. First, all Edg was identified with exception of Edg6. Moreover, the cAMP level was unchanged by LPA per se, whereas co-incubation with forskolin generated a rapid and transient response. Further, SIP generated a divergent response including a LPA equivalent mitogen effect at low concentrations whereas inhibition of DNA replication was obtained at higher concentrations.In summary, this project demonstrates that cyclic nucleotides inhibit smooth muscle hyperplasia/hypertrophy in the luogenital tract. These results also suggest that manipulation of cyclic nucleotide level using tissue specific PDE inhibitors might constitute a new therapeutic approach for hyperplasia/hypertrophy related diseases in the urogenital tract.
  • Ahlgren, Ewa, 1959- (författare)
  • Cerebral complications after cardiac surgery
  • 2002
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Cerebral injuty remains a major cause of morbidity and mortality after cardiac surgery. Previous studies have mainly focused on preoperative risk factors and intraoperative events but cerebral complications may also occur in the postoperative period. Cognitive impairment is common after cardiac surgery but the consequences of this complication for activities of daily life are less known. Safe driving involves a complex set of skills requiring preserved cognitive function. A substantial number of patients with heart disease are active drivers. The impact of postoperative cognitive dysfunction on driving performance, however, has not previously been investigated in this large patient group.In this thesis pre-, intra- and postoperative risk factors for focal cerebral complications were determined and the onset time of cerebral symptoms were evaluated in two cohorts of cardiac surgical patients, comprising 2480 and 3282 patients respectively. Data analysed were drafted from a clinical register and the surgical database of Linköping University Hospital Heart Center. Cerebral complication was delayed, i.e occurred after a free interval, in about one third of patients suggesting causes other than intraoperative events. Different risk factors were found for early and delayed cerebral complications suggesting different mechanisms of cerebral injury. Advanced age, preoperative hypertension, aortic surgery, prolonged cardiopulmonary bypass (CPB) time, intraoperative hypotension after completion of CPB, and arrhytlunia in the early postoperative period increased the risk for early cerebral complication. Female gender, diabetes, previous cerebrovascular disease, combined coronary artery bypass grafting (CABG) and valve surgery and arrhythmia on the thoracic ward increased the risk for delayed cerebral complication. Cognitive function and driving performance were evaluated in 27 patients before and 4-6 weeks after CABG. The patients underwent neuropsychological testing, an on-road driving test and a test in an advanced driving simulator. Twenty patients scheduled for percutaneous coronary intervention (PCI) served as controls. Complete data were obtained in 23 and 19 patients respectively. Furthermore cognitive function and driving performance in on-road driving of the 44 patients with complete tests before intervention were compared with controls of similar age without heart symptoms. Cognitive function and driving performance were already impaired in patients with coronary artery disease before intervention when compared with controls. After surgery 48% of the patients showed cognjtive decline compared to 10% after PCI. These patients also scored less in the on-road driving test to a greater extent than did patients without postoperative cognitive decline.
  • Ahmadi, Ahmad, 1964- (författare)
  • Genetic predisposition and risk factors for neurodegenerative diseases
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The inter-individual variability in biotransformation, may lead to differences in activation and detoxification of both endogenous and exogenous compounds. Polymorphism studies in such genes were applied for Parkinson's disease (PD) and Chronic toxic encephalopathy (CTE), two diseases influenced by both genetic and enviromnental factors.An elevated median age for the onset of PD was found among GS1M1 gene carriers compared to PD patients being GS1M1 null genotypes (68 years versus 57 years). No similar difference was found for GSTT1. mEPHX (113HH) isoform, which has been suggested as a low activity variant, is over represented in PD patients (OR=3.8, CI 95%, 1.2-11.8).Monoamine oxidases (MAO-A and -B) are important in the dopamine metabolism and in the detoxification of neurotoxins and genetic variants in these genes have earlier been assigned to PD. However, no difference was revealed between any of the polymorphisms studied in the MAO-A and -B genes and PD. Smoking displayed an enviromnental exposure with a strong decreased risk for PD in this study (OR=0.40 for men and OR=0.48 for women) but no obvious interaction with the MAO genotypes could be observed.Mitochondrial dysfunction and oxidative stress have been hypothesized to contribute to the pathogenesis of PD. The superoxide dismutases (SOD) potentially play an important role in PD by detoxifying superoxide radicals in mitochondria. Polymorphisms neither in superoxide dismutase 2 (SOD2) nor mitochondrial complex I subunit, NDUFV2, were associated with PD.An increased risk ratio for CTE was found in smokers with the GSTM1 null genotype (RR=2.5, Cl 95%, 1.4-4.2) or the GSTT1 null genotype (RR=1.4, Ci 95%, 1.02-2.0). In non-smokers GS1M1 null genotype did not confer any risk for CTE. Polymorphisms in mEPHX were not associated with an increased risk for CTE.Thus, various genetic and enviromnental factors most likely influence both PD and solvent-induced CTE. Detoxification pathways may represent important protective mechanisms against reactive intermediates, thus genetic predisposition in these pathways could modify the susceptibility and onset of PD and solvent-induced CTE.
  • Alehagen, Siw, 1953- (författare)
  • Fear pain stress hormones during labor
  • 2002
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The aims of the thesis were to develop a measure of fear during labor and to investigate women's experiences of fear and pain during labor and delivery as well as their levels of stress hormones. We also wanted to explore the associations between fear, pain, stress hormones and the duration of labor. Finally, we aimed to examine the relationships between pre-and postpartum fear, and fear and pain during labor.The measurement of fear was developed in two substudies. First we composed a list of 60 fear-related items and their contrasts and tested it in a group of 92 women in labor. After psychometrical analyses, 10 items were selected for the final scale. The scale was then tested in another group of 57 women in labor. Via semi-structured interviews the content of the items was documented and analyzed.Fifty-five nulliparous women participated in the investigation of women's experiences of fear, pain, levels of stress hormones and duration of labor. During gestation weeks 37-39, we measured levels of fear of childbirth, urinary catecholamines and salivary cortisol. During labor, hourly measurements were performed of fear, pain and levels of stress hormones. Finally, at two hours, two days and five weeks postpartum, fear of childbirth and stress hormones were measured.The questionnaire that measures fear during labor was called the Delivery Fear Scale (DFS). The DFS has an alpha coefficient of .8 and has good psychometric qualities in both nulliparous and parous women. It takes women in labor between 30 and 90 seconds to listen to and answer all the statements. We found that nulliparous women had higher fear during phase 1 of labor (cervix dilatation 3-Scm) than parous women. Fear during phase 1 of labor predicted the total amount of pain relief received during labor, but not the duration of remaining part of labor, nor the occurrence of instrumental vaginal delivery or emergency cesarean section.The results from the subsequently studies showed that there was an increase of the levels in stress hormones from pregnancy to labor. Epinephrine and cortisol increased more than 500% and norepinephrine approximately 50%. In women without EDA fear and cortisol increased throughout labor. In women with EDA cortisol did not increase, fear, pain and catecholamine levels first decreased after the administration of EDA but at the end of labor fear and pain increased. In phase 1, fear, but not pain, was more intensive in women who later subsequently received EDA than in those who did not. Fear and pain correlated positively during labor. A high level of epinephrine was associated with a shorter duration of phase 1 of labor. Postpartum fear of childbirth was higher in women who had received EDA during labor than in those who had not. Pre- and postpartum fear of childbirth correlated positively with fear but not with pain during phase 1 of labor.In conclusion, DFS is a new measure of fear during labor with good psychometric qualities. Childbirth is a stressful event associated with exceptionally high levels of stress hormones. In this study women's experiences of fear and pain were associated throughout labor. The administration of EDA heavily influenced the course of fear, pain and stress hormones. Women who later received EDA had higher scores of fear but not of pain early during labor than those who did not receive EDA. Late pregnant women who fear childbirth are prone to have a fearful delivery, as reported during the actual labor and postpartwn.
  • Alehagen, Urban, 1951- (författare)
  • Heart failure in primary health care : special emphasis on natriuretic peptides in the elderly
  • 2003
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Background: This thesis focuses on heart failure among elderly patients in the community who usually are not included in studies on heart failure. The heart failure syndrome is an increasing problem in Western society. Severe heart failure is often easy to diagnose compared with light to moderate heart failure, which is more frequent in patients in the community,Doppler echocardiography is the most commonly used method to objectively verify an abnormal cardiac function, mostly the systolic function. One goal of this thesis was to evaluate both the systolic and diastolic functions. Another goal was a study of the possible utility of the B-type natriuretic peptide, BNP (brain natriuretic peptide), and the amino terminal fragment of its precursor, proBNP (N-terminal proBNP) as tools in the diagnosis of heart failure in elderly patients.Methods: In a primary health care setting, 510 elderly patients (age range 65-82 years) with symptoms and signs possibly associated with heart failure were examined concerning patient history, ongoing pharmacological treatment, clinical examination, chest x-ray, electrocardiogram, Doppler echo cardiography, and selected biochemical measurements of blood samples. Additionally, the natriuretic peptide BNP and the aminoterminal fragment of proBNP were analyzed for a possible influence of gender, age, impaired cardiac function assessed using Doppler echocardiography, other diseases, and phannacological treatment. We followed our study population for six years, carefully registering mortality with death certificates. This information was used in analyzing the risk of cardiovascular death based on Cox proportional hazard regression. We present a model for estimating the risk of cardiovascular death in the individual patient.Results: Almost half of our study population [mean age 73 (SD 6) years] with symptoms of possible heart failure had signs of impaired cardiac function on Doppler echocardiography. Half of these individuals had isolated impairment of the diastolic function. Almost two thirds of the elderly patients who had an ejection fraction of less than 40% did not receive treatment with ACE inhibitors, one of the cornerstones in the treatment of heart failure.BNP and N-terminal proBNP were equally effective in detecting impaired cardiac function. As a response to increased filling pressure they probably provide earlier information on the haemodynamic situation than Doppler echocardiography does.In these elderly patients, functional class (NYHA class III: 7 times increased risk), in vivo examination by Doppler echo cardiography (EF<30%: 8 times increased risk) and the in vitro measurement of plasma BNP (>27.8 pmol/L: 11 times increased risk) and N-terminal proBNP (>109 pmol/L: 7 times increased risk) could be used as prognostic determinants in assessing the risk of cardiovascular death.Conclusion: The results indicate that a focused patient history and clinical examination provides important information that is often sufficient for the prognostic evaluation of a patient with heart failure symptoms. Additional information may be obtained with Doppler echo cardiographic examination and measurement of plasma BNP or N-terminal proBNP. The relationship between BNPIN-terminal proBNP concentration and risk of cardiovascular death may be analysed to define decision limits for the concentrations of these peptides as regards further diagnostic procedures and/or phannaceutical treatment.
  • Alkaissi, Aidah, 1953- (författare)
  • Postoperative Symptoms After Gynaecological Surgery How They Are Influenced by Prophylactic Antiemetics Sensory Stimulation (P6-Acupressure)
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Symptoms after surgery and anaesthesia influence the patient´s ability to resume daily activities. If postoperative symptoms are controlled rehabilitation may be accelerated. The aims of this dissertation were to identify disturbing symptoms reported by patients after gynaecological surgery, to investigate what effect prohylactic treatment with antiemetics has on these symptoms and whether or not sensory simulation of the P6-acupressure has an effect on postoperative nausea and vomiting (PONV) and motion sickness.Methods: Total 1138 women participated in three clinical trials (Studies I, II, III) and one experimental study (Study IV). A questionnaire investigating postoperative symptoms was constructed and validated. The questionnaire was used in a prospective, consecutive, doubleblind, randomised, multicentre, and controlled study to identify incidence, and intensity of postoperative symptoms and the effect of common antiemetics (droperidol and granisetron) (Study III). The patients were followed for 24 h. In two studies (I, II) P6-acupressure was compared (prospective, double-blind, ransomised, controlled) with placebo acupressure and a reference group where the effect on PONV was followed over 24 h. The effect of P6-acupressure and placebo acupressure on motion sickness induced by a nauseogenic motion challenge was studied (Study III).Results: A high incidence and severity of postoperative symptoms were found after gynaecological surgery in a group with a high risk (>30%) for PONV. Sixty-four per cent (107/165) of the patients experienced disturbing symptoms after surgery and 46 % (76/165) scored their symptoms as moderate to very severe. Fourty-eight per cent (79/165) had two or more symptoms. A higher incidence of symptoms were reported in the groups with prophylactic treatment, granisetron 74% (123/165) and droperidol 80% (133/165) compared to the control group 41% (69/165) (P <0.05). The relative risk reduction for PONV with granisetron or droperidol prophylaxis is 27% respective 22%. The relative risk increase for headache is 63% after granisetron, and 44% for difficulty with accommodation after droperidol. Less PONV was seen after P6-acupressure, 33% (44/135) compared to reference group 46% (63/136) (p = 0.019), number needed to treat (NNT) was 7 [95% confidence interval (CI) 4- 6]. When comparing laparoscopic and vaginal surgery (subgroup analysis) the main effect was in the vaginal group (day-case surgery), 36% (27/75) in the reference group to 27% (23/86) in the placebo group and to 20% (17/84) in the P6-acupressure group, (P = 0.017), NNT for the vaginal group was 6 [95% CI 3-18]. P6-acupressure increased time to nausea after a laboratory motion challenge and reduced the total number of symptoms reported (p <0.009).Conclusions: There is no clinical efficacy in the form of reduced postoperative symptoms after prophylactic antiemetics (droperidol and granisetron) in females with a high risk (>30%) for PONV undergoing gynaecological surgery. P6-acupressure reduces the incidence of PONV after gynaecological surgery in females with a high (>30%) risk for PONV. The effect seems to be most prominent after vaginal surgery. P6-acupressure increased tolerance to experimental nausogenic stimuli and reduced the total number of symptoms reported in females with a history of motion sickness.
  • Almroth, Gabriel, 1953- (författare)
  • Immunoglobulins, immunoglobulin subclass-distributions and serologic markers in some renal and systemic disorders
  • 2000
  • Doktorsavhandling (övrigt vetenskapligt)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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