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51.
  • Alexandersson, Kristina (författare)
  • Sickness absence in a Swedish county : with reference to gender, occupation, pregnancy and parenthood
  • 1995
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The occurrence of sickness absence in relation to gender, occupation, age, pregnancy and parenthood was analysed in a Swedish county. Data on all new sick-leave spells exceeding 7 days in the county of Östergötland (400,000 inhabitants) were recorded in 1985-1987. Information on diagnoses, occupation, age, gender, number of children etc. for each of the 45,000 persons sicklisted/year were included in the database. Incidence measures were obtained using census data as denominator.The largest and most consistent variation in occurrence of sickness absence concerned occupation and gender, When categorising the occupations according to degree of gender-segregation, women in the extremely maledominated group (>90% men) had exceptionally high sick-leave rates, while both men and women in the group of gender-integrated occupations had significantly lower sick-leave rates. These variations with male-and female domination of occupational groups were found for sickness absence in general as well as for sick-leave due to pregnancy-related diagnoses. Men with custody of young children had the lowest sickness absence, young women in the same situation the highest, while there were no gender differences in persons without young children. Sickness absence due to pregnancy-related diagnoses varied to a large degree with occupation, but was still high in occupations with a generally low sickness absence, and increased much more than in any otherdiagnostic group over the three years. About half of the gender differences in sickness absence could be explained by sickness absence among pregnant women.In conclusion, the occurrence of sickness absence was associated with gender, age, occupation, gender segregation of occupation, pregnancy and parenthood. Further research should focus on etiological studies and intervention trials.
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52.
  • Alfredsson, Joakim (författare)
  • Management and Outcome in Non ST-Elevation Acute Coronary Syndromes Similarities and Differences Between Women and Men
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Background: Non ST-elevation Acute Coronary Syndromes are the most frequent manifestations of acute ischemic heart disease. Gender differences in treatment intensity, including differences in level of care, have been reported. Also differences in benefit from certain treatments, especially invasive treatment, have been discussed. Finally, difference in outcome between men and women, have been proposed. Results have been inconsistent, partly depending on if and how adjustment for differences in background characteristics has been made. The aims of the studies in this thesis were to assess differences between the genders in baseline characteristics, level of care, medical treatment and non-invasive and invasive cardiac procedures. The aims were also to determine gender differences in short and long-term mortality, including impact of level of care, and to determine differences between the genders in benefit from an invasive strategy, with special reference to benefit in women.Method: We used prospectively collected data from the RIKS-HIA registry in two studies (Paper I and IV). In one study we merged data from patients admitted to general wards in the south-east region of Sweden (The AKUT registry), with data from patients admitted to CCU´s (RIKS-HIA) at participating hospitals during the same time (Paper II). We also randomly assigned women to a routine invasive or a selective invasive treatment strategy, and performed a meta-analysis, to determine gender differences in benefit from a routine invasive strategy (Paper III).Results: Women were older than men and more likely to have a history of diabetes and hypertension, while men were more likely to have a history of myocardial infarction and revascularisation. Women were also more likely to have normal coronary arteries on the angiogram. After adjustment for baseline differences there were only minor, and directionally inconsistent, differences between women and men in pharmacological treatment. Men were more often referred for coronary angiography, even after adjustment. While CABG-rate was lower in women, after adjustment PCI-rate was similar or even higher compared to men. After adjustment for differences in age, longterm outcome was better in women. In our small but randomised trial there was no benefit from a routine invasive strategy in women. A meta-analysis indicated interaction between gender and treatment strategy, with lack of benefit in women, in contrast to in men. However, our large observational study indicated no gender difference with an invasive strategy. Moreover, benefit was similar in women and men with invasive treatment.Conclusion: There are substantial differences between women and men in baseline characteristics that affect management and outcome more than gender per se. After adjustment women have better long-term outcome than men. There appear to be a difference in benefit from a routine invasive strategy between the genders, with less benefit in women, but in routine clinical management there was no difference between women and men managed with an invasive strategy.
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53.
  • Ali, Zaheer, 1984- (författare)
  • Investigating mechanisms of angiogenesis in health and disease using zebrafish models
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Angiogenesis, the growth of blood vessels from an existing vasculature, can occur by sprouting from preexisting vessels or by vessel splitting (intussusception). Pathological angiogenesis drives choroidal neovascularization (CNV) in age related macular degeneration (AMD) which is commonly restricted under the retinal pigment epithelium (RPE), called occult CNV, but may also involve vessels penetrating through the RPE into the sub-retinal space. Pathological vessels are poorly developed, insufficiently perfused and highly leaky, phenotypes that are considered to drive disease progression and lead to poor prognosis. Currently, a number of anti-angiogenic drugs exists, the majority of which target vascular endothelial factor (VEGF), but although they often are highly beneficial for treating eye diseases in the short-term, they are generally of limited efficacy in other diseases such as cancer, and also have poorer efficacy when used for treatment of eye diseases in the long-term. A better understanding of the mechanisms underlying pathological angiogenesis can generate new targets for treatment leading to development of better drugs for cancer and retinopathies, but perhaps also other angiogenesis-dependent diseases, in the future. In this thesis mechanisms involved in developmental angiogenesis or pathological angiogenesis in the choroid, cornea or melanoma was identified. These findings highlight the need to further elaborate our knowledge related to angiogenesis in different tissues/conditions for a more targeted, and potentially effective treatment of diseases in the future.In paper I, we for the first time identified the choriocapillaries (CCs) in adult zebrafish and found that occult CNV could be induced by exposing the fish to severe hypoxia. Interestingly, we found that occult CNV relied on intussusception, involving not only de novo generation of intussusceptive pillars but also a previously poorly understood mechanism called pillar splitting. This involved HIF-VEGF-VEGFR2 signaling and evidence that this also occurred in both rats and humans suffering from AMD suggested that the mechanism was conserved and clinically relevant.In contrast, we found in paper II that the development of CCs in the zebrafish relies on sprouting angiogenesis, involve continuous remodeling, and delayed maturation of the vasculature in 2D. The initial development was found to occur by a unique process of tissuewide synchronized vasculogenesis. As expected, VEGFA via VEGFR2 was also critical for the development of these vessels in the zebrafish embryo, but surprisingly this was independent on hypoxia-inducible factor (HIF)-1.Inflammatory nuclear factor-kB (NF-kB) signaling is involved in the progression of angiogenesis, but this signaling pathway has mainly been studied in the inflammatory cells and the role of NF-kB in the endothelial cells during angiogenesis is poorly understood. In paper III, we found that blocking NF-kB signaling using a specific IKK2 blocker IMD0354, specifically blocks pathological as well as developmental angiogenesis by targeting endothelial cell NF-kB signaling in the endothelial cells. Using a rat model for suture-induced corneal neovascularization, IMD0354 treatment lead to reduced production of inflammatory C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 5 (CXCL5) and VEGF, and thereby reduced pathological corneal angiogenesis in this model.Using the zebrafish tumor xenograft model in paper IV, we found an association between Microphthalmia associated transcription factor (MITF) and pigment epithelium derived factor (PEDF), which was involved in pathological tumor angiogenesis and metastasis. Similarly, in paper V we used zebrafish transplantation models to study and investigate the use of biocompatible polymers for the delivery of pro-angiogenic FGF-2 as a potential treatment strategy for ischemic diseases such as myocardial infarction (MI). Conclusively, this thesis provides new insights into diverse fields of angiogenic assays using zebrafish, and reveals new mechanisms of angiogenesis in health and disease. This work will hopefully provide a foundation for further studies into occult CNV related to AMD, a process that has not been possible to study previously in pre-clinical models. In addition, zebrafish xenograft or other transplantation models used in this work will likely be important to study cancer biology and to develop more attractive pharmaceutical preparations based on biocompatible hydrogels formulated as microspheres in the future.
54.
  • Aljabery, Firas (författare)
  • Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Aim: To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data.Patients and Methods: We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome.Results: Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases.Conclusion: PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.
55.
  • 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.
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56.
  • Alkaissi, Hammoudi, 1983- (författare)
  • Identification of candidate genes involved in Mercury Toxicokinetics and Mercury Induced Autoimmunity
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • BACKGROUND: Autoimmune diseases require the involvement and activation of immune cells and occur when the body builds up an immune response against its own tissues. This process takes place due to the inability to distinguish self-antigen from foreign antigen. Systemic autoimmunity represents an important cause of morbidity and mortality in humans. The mechanisms triggering autoimmune responses are complex and involve a network of genetic factors. Genome wide association study (GWAS) is a powerful method, used to identify genetic risk factors in numerous diseases, such as systemic autoimmune diseases. The goal of GWAS is to identify these genetic risk factors in order to make predictions about who is at risk and investigate the biological process of disease susceptibility. There are several valuable mouse models to investigate the underlying mechanisms causing systemic autoimmune diseases in which mercury induced autoimmunity (HgIA) is a well- established and relevant model. HgIA in mice includes development of autoantibodies, immune complex glomerulonephritis, lymphocyte proliferation, hypergammaglobulinemia and polyclonal B cell activation. In humans, mercury exposure accumulates with considerable concentrations in kidney, liver, and brain. Toxicokinetics of Hg has been studied extensively but the key for inter-individual variation in humans are largely unclear. Differences in accumulation of renal Hg between inbred mouse strains suggest a genetic inter-strain variation regulating retention or/and excretion of Hg.OBJECTIVES: To find loci and candidate genes associated with phenotypes involved in the development of autoimmunity and find candidate genes involved in the regulation of renal Hg excretion.METHODS: MHC II (H-2s) mice were paired (A.SW x B10.S) to obtain F2 offspring exposed to 2.0 or 4.0 mg Hg in drinking water for 6 weeks. Mercury induced autoimmune phenotypes were studied with immunofluorescence (anti-nucleolar antibodies (ANoA)), ELISA anti-DNP/anti-ssDNA (polyclonal B cell activation), anti-chromatin antibodies (ACA) (4.0 mg Hg), and serum IgG1 concentrations. Mercury accumulation in kidney was performed previously and data was included as phenotype. F2 mice exposed to 2.0 mg Hg were genotyped with microsatellites for genome-wide scan with Ion Pair Reverse Phase High Performance Liquid Chromatography (IP RP HPLC). F2 mice exposed to 4.0 mg Hg were genotyped with single nucleotide polymorphisms for genomewide scan with SNP&SEQ technology platform. Quantitative trait loci (QTL) was established with R/QTL. Denaturing HPLC, next generation sequencing, conserved region analysis and genetic mouse strain comparison were used for haplotyping and fine mapping on QTLs associated with Hg concentration in kidney, development of ANoA and serum IgG1 hypergammaglobulinemia. Candidate genes (Pprc1, Bank1 and Nfkb1) verified by additional QTL were further investigated by real time polymerase chain reaction. Genes involved in the intracellular signaling together with candidate genes were included for gene expression analysis.RESULTS: F2 mice exposed to 2.0 mg Hg had low or no development of autoantibodies and showed no significant difference in polyclonal B cell activation in the B10.S and F2 strains. F2 mice exposed to 4.0 mg Hg developed autoantibodies and significantly increased IgG1 concentration and polyclonal B cell activation (anti-DNP). QTL analysis showed a logarithm of odds ratio (LOD) score between 2.9 – 4.36 on all serological phenotypes exposed to 4.0 mg Hg, and a LOD score of 5.78 on renal Hg concentration. Haplotyping and fine mapping associated the development of ANoA with Bank1 (B-cell scaffold protein with ankyrin repeats 1) and Nfkb1 (nuclear factor kappa B subunit 1). The serum IgG1 concentration was associated with a locus on chromosome 3, in which Rxfp4 (Relaxin Family Peptide/INSL5 Receptor 4) is a potential candidate gene. The renal Hg concentration was associated with Pprc1 (Peroxisome Proliferator-Activated Receptor Gamma, Co-activator-Related). Gene expression analysis revealed that the more susceptible A.SW strain expresses significantly higher levels of Nfkb1, Il6 and Tnf than the less susceptible B10.S strain. The A.SW strain expresses significantly lower levels of Pprc1 and cascade proteins than the B10.S strain. Development of ACA was associated with chromosomes 3, 6, 7 and 16 (LOD 3.1, 3.2, 3.4 and 6.8 respectively). Polyclonal B cell activation was associated with chromosome 2 with a LOD score of 2.9.CONCLUSIONS: By implementing a GWAS on HgIA in mice, several QTLs were discovered to be associated with the development of autoantibodies, polyclonal B cell activation and hypergammaglobulinemia. This thesis plausibly supports Bank1 and Nfkb1 as key regulators for ANoA development and HgIA seems to be initiated by B cells rather than T cells. GWAS on renal mercury excretion plausibly supports Pprc1 as key regulator and it seems that this gene has a protective role against Hg.
57.
  • Alkhori, Liza (författare)
  • Mechanisms of sensory neuron diversification during development and in the adult Drosophila How to make a difference
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The nervous system contains a vast number of neurons and displays a great diversity in cell types and classes. Even though this has been known for a long time, the exact mechanism of cell specification is still poorly understood. How does a cell know what type of neuron to which it should be specified? It is important to understand cellular specification, not only for our general understanding of biological processes, but also to allow us to develop treatments for patients with destructive diseases, such as Alzheimer’s, Parkinson, cancer or stroke. To address how neuronal specification and thereby diversification is evolved, we have chosen to study a complex but defined set of neurons, the Drosophila olfactory system. Olfactory sensory neurons (OSNs) detect an enormous variety of small volatile molecules with extremely high specificity and sensitivity. The adult Drosophila olfactory system contains 34 OSN classes each defined by their expression of a specific odorant receptor (OR). In both insects and vertebrates, each OSN expresses only one OR. In mouse there are approximately 1200 and in Drosophila 60 different OR genes. Despite the range of mechanisms known to determine cell identity and that the olfactory system is remarkably conserved across the phyla, it is still unclear how an OSN chooses to express a particular OR from a large genomic repertoire. In this thesis, the specification and diversification of the final steps establishing an OSN identity is addressed. We find seven transcription factors that are continuously required in different combinations for the expression of all ORs. The TFs can in different gene context both activate and repress OR expression, making the regulation more economical and indicating that repression is crucial for correct gene expression. We further identified a repressor complex that is able to segregate OR expression between OSN classes and propose a mechanism on how one single co-repressor can specify a large number of neuron classes.Exploring the OSN we found the developmental Hh signalling pathway is expressed in the postmitotic neuron. We show several fundamental similarities between the canonical Drosophila Hh pathway and the cilia mediated Hh transduction in component function. Further investigation revealed a function of cilia mediated Hh signalling in sensory neuron modulator. The results generated here will create a greater in vivo understanding of how postmitotic processes generate neurons with different fates and contribute to the maintaining of neuron function.
58.
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59.
  • Almer, Sven, 1953- (författare)
  • Ulcerative colitis : Imaging of inflammation
  • 1995
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Ulcerative colitis is a chronic inflannnatory disorder of unknown origin engaging the large bowel. Based on the need for accurate assessment of inflammation, three different non-invasive techniques, two leukocyte scintigraphy techniques and one radiological method, were evaluated in the assessment of active inflammation in altogether 131 patients with ulcerative colitis. Results were compared to those of endoscopy with biopsy, and with histopathological grading of depth of ulceration in colectomy specimens. Nine non-inflamed controls were also includedLeukoeyte scintigraphy using technetium-99m exarnetazime-labelled lenkocytes was found to reliably differ between patients with and without colonic inflammation. A good correlation existed between a simple visual scoring system of lenkocyte scans and colonic inflannnation viewed endoscopically and histologically in ulcerative colitis. In active disease, inflammation was better visualized with technetiurn-99m exametazimelabelled leukocytes than with technetium-99m anti-granulocyte antibody BW 250/183.Air enema radiology was of value in estimating severe mucosal inflammation in acute ulcerative colitis. Presence of faecal residue or a normal air enema film were associated with normal or only mildly inflamed mucosa at colonoscopy, i.e. a friable or ulcerated mucosa can be excluded. The absence of faecal residue or an abnormal finding at air enema X-ray were predictive of endoscopically inflamed mucosa. Air enema radiology underestimated the extent of inflannnation compared to endoscopy or lenkocyte scintigraphy. Air enema radiology was able to demonstrate presence of deep histopathological ulceration in the colectomy specimens from patients with an acute attack of ulcerative colitis.In conclusion, scintigraphy with technetium-99m exarnetazime-labelled lenkocytes can be applied in excluding or confirming bowel inflammation in individual patients, and, in assessing intensity and extent of ulcerative colitis. Air enema radiology should be a first-line investigation in acute colitis to assess the presence of mucosal or deeper ulceration.
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60.
  • 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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