| 31. |
- Carlsson, Björn, 1975-
(författare)
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From achiral to chiral analysis of citalopram
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Within the field of depression the “monoamine hypothesis” has been the leading theory to explain the biological basis of depression. This theory proposes that the biological basis of depression is due to a deficiency in one or more of three key neurotransmitter systems, namely noradrenaline, dopamine and serotonin which are thought to mediate the therapeutic actions of virtually every known antidepressant agent.Citalopram is a selective serotonin-reuptake inhibitor (SSRI) used for the treatment of depression and anxiety disorders. Citalopram is a racemic compound, in other words composed of a 50:50 mixture of two enantiomers (S-(+)-citalopram and R-(-)-citalopram) and with one of the enantiomers (S-(+)-citalopram) accounting for the inhibitory effect. At the time of introduction of citalopram the physician needed a therapeutic drug monitoring service to identify patients with interactions, compliance problems and for handling questions concerning polymorphic enzymes and drug metabolism. An achiral analytical separation method based on solid-phase extraction followed by high-performance liquid chromatography (HPLC) was developed for routine therapeutic drug monitoring (TDM) of citalopram and its two main demethylated metabolites.As the data available on citalopram were from achiral concentration determinations and to be able to further investigate citalopram enantiomers effects and distribution, a chiral method for separation of the enantiomers of citalopram and its demethylated metabolites was established. The advances within chiral separation techniques have made measurement of the concentrations of the individual enantiomers in biological fluids possible.The process behind enantioselective separation is however not fully understood and the mechanism behind the separation can be further scrutinized by the use of multivariate methods. A study of the optimization and characterization of the separation of the enantiomers of citalopram, desmethylcitalopram and didesmethylcitalopram on an acetylated ß-cyclodextrin column, by use of two different chemometric programs - response surface modelling and sequential optimization was performed. Sequential optimization can be a quicker mean of optimizing a chromatographic separation; response surface modelling, in addition to enabling optimization of the chromatographic process, also serves as a tool for learning more about the separation mechanism.Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent, despite the increasing use of citalopram in these age groups.A study was initiated to investigate adolescents treated for depression, with respect to the steady-state plasma concentrations of the enantiomers of citalopram and its demethylated metabolites. The ratios between the S- and R-enantiomers of citalopram and didesmethylcitalopram were in agreement with studies involving older patients. The concentrations of the S-(+)- and R-(-) enantiomers of citalopram and desmethylcitalopram were also in agreement with values from earlier studies. The results indicate that the use of oral contraceptives may have some influence on the metabolism of citalopram. This might be because of an interaction of the contraceptive hormones with the polymorphic CYP2C19 enzyme.Even though the SSRIs are considered less toxic compared with older monoamine-active drugs like the tricyclic/tetracyclic antidepressants, the risk of developing serious side effects such as ECG abnormalities and convulsions has been seen for citalopram, when larger doses have been ingested. Furthermore, fatal overdoses have been reported where citalopram alone was the cause of death. Data on the toxicity of each of the enantiomers in humans have not been reported and no data on blood levels of the enantiomers in cases of intoxication have been presented.An investigation was initiated on forensic autopsy cases where citalopram had been found at the routine screening and these cases were further analysed with enantioselective analysis to determine the blood concentrations of the enantiomers of citalopram and metabolites. Furthermore the genotyping regarding the polymorphic enzymes CYP2D6 and CYP2C19 were performed.In 53 autopsy cases, we found increasing S/R ratios with increasing concentrations of citalopram. We found also that high citalopram S/R ratio were associated with high parent drug to metabolite ratio and may be an indicator of recent intake. Only 3.8 % were found to be poor metabolizers regarding CYP2D6 and for CYP2C19 no poor metabolizer was found.Enantioselective analysis of citalopram and its metabolites can provide valuable information about the time that has elapsed between intake and death. Genotyping can be of help in specific cases but the possibility of pharmacokinetic interactions is apparently a far greater problem than genetic enzyme deficiency.
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| 32. |
- Casas, Rosaura, 1954-
(författare)
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Transfer of humoral immunity from the mother to her off-spring
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background. It has been established that T cell responses of foetal origin to inhalant allergens are present in most cord blood samples. These immune responses could possibly be explained by transplacental passage of peptides, either as free antigens or in complexes with IgG, providing the foetus with a trigger for the priming of the T cell system already in utero. Antibodies to food antigens to which the mother is commonly exposed are present in the milk, but their relationship to allergy is unknown. IgA antibodies to inhalant allergens have not been previously detected in human milk.Objective. The aim of this thesis was to explore whether inhaled allergens in serum and IgA antibodies in breast milk could contribute to the allergic immune responses to allergens in the children.Methods. The presence of cat allergen Fel d 1 was analysed by ELISA in serum samples from cat allergic asthmatic children. To detect IgG immune complexes (IC), affmity chromatography purification and Western blotting were performed. Iri:nnune complexes with Fel d 1-IgE were detected by a modification of MagicLite, and their specificity was assessed by different approaches. Serum samples from allergic and non-allergic mothers, and cord blood from their infants, were measured for the presence of Fel d 1-IgG immune complexes by an amplified ELISA. Cord blood mononuclear cells (CBMC) of babies from allergic and non-allergic mothers were stimulated with cat allergen and the production of IFN-γ, IL-5, IL-10 and IL-13 was determined by ELISA and the levels related to the presence of IC. Furthermore, IgG1 and IgG4 antibodies to cat were measured by ELISA. Colostrum and samples of mature milk from allergic and non-allergic mothers were analysed for IgA antibodies to cat, P-lactoblobulin (BLG) and ovalbumin (OVA) by an amplified ELISA.Results. The cat allergen Fel d I was detected in 70% of sera from cat allergic chilch'en, but not in any of the controls. The allergen was present in complexes with IgE and IgG antibodies as corroborated by different approaches. Immune complexes with IgG were detected in sera from allergic and non-allergic mothers, as well as in the cord blood from their babies, but neither the prevalence nor the levels of complexes were related to maternal allergy. This was also the case for IgG antibodies to cat. The production of IL-5, IL-10, IL-13 and IFN-γ by CBMC was not influenced by maternal atopy. Interferon-y secretion by CBMC after stimulation with cat allergen, however, was less conunonly detected in samples with immune complexes. Secretory IgA to cat and OVA allergens were frequently detected in colostrum and mature milk, while antibodies to BLG were less common. The antibody levels to cat and BLG were similar in allergic and non-allergic mothers.Conclusion. The presence of IC with allergens may contribute to maintaining immune responsiveness and sensitivity in allergic individuals. Low levels of transplacentally transferred IC can conceivable provide the foetus with the signal for priming ofT cell responses to inhalant allergens. This seems to be a nonnal mechanism, as the immune responses are not related to maternal allergy. Low level exposure of the maternal mucosa, e.g. by inhalant allergens, can induce IgA antibody secretion in breast milk, but this mechanism is not related with any protective effect against allergy.
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| 33. |
- Cederbrant, Karin, 1964-
(författare)
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The Primary Lymphocyte Culture in the Diagnosis of Drug- and Metal-Induced Allergy
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Drugs and metals are examples of xenobiotics that can induce hypersensitivity in humans. These adverse reactions are classified as allergy if repeated exposure leads to the same type of clinical manifestation. Together with the clinical history, the skin test is the most commonly used test for the diagnosis of allergic disease. However, in vivo testing per se has drawbacks such as the risk of potentiation of the allergy or even sensitisation to a given test substance. For this reason in vitro testing is an attractive diagnostic alternative since it does not involve any exposure of the test subject to the allergen.The lymphocyte transformation test (LTT) has been used to complement the diagnosis of allergy to drugs and metals for more than thirty years. The principle behind this test is to show the presence of allergen-specific memory lymphocytes in peripheral blood, which is a sine qua non of a true allergy. LTT reveals the proliferation of such cells by showing DNA synthesis as the uptake of 3H-thymidine in primary PBMC (peripheral blood mononuclear cell) cultures treated with the allergen. However, LIT has not yet been generally accepted as a stand-alone test in the diagnosis of allergy. One reason for this is that different chemical properties of the allergens may lead to either false positive or false negative LTT responses.In the present study we investigated allergy to the drug bacampicillin and to the metals Au, Pd, Ni and Hg. Three different protocols for LTT: LIT in micro cultures (LTT-micro), LTT in macro cultures (LTT-macro) and memory lymphocyte immunostimulation assay (MELISA) were compared using a skin test or clinical history as reference methods. LTI showed a sensitivity of 87% and a specificity of 90% when used in the diagnosis of allergy to bacampicillin. When allergy to Au, Pd, Ni and Hg was investigated, the sensitivity was 33- 95% and the specificity 0-79%. There were no significant differences between the test protocols, except that MELISA showed a significantly higher specificity than LTT-micro and LTT-macro when Hg2+ was used as antigen. Even so, this specificity was only 70%, which would result in 30 of 100 healthy subjects receiving a false diagnosis of Hg allergy when using the MELISA protocol. Ni2+ also induced high numbers of false-positive LTI responses, 77-85% patch-test negative subjects showed positive results to these metals. However, group comparisons showed a significantly higher proliferation intensity in allergic than in nonallergic groups for all allergens except Hg2+. Furthermore, only 56% of patients with verified allergy to mercury showed a positive MELISA, a sensitivity that is unacceptably low.Following these findings, we investigated whether other endpoints than DNA synthesis could be used to discriminate allergic from healthy subjects, using primary PBMC cultures with Hg2+ or Ni2+ as a model system. Analysis of the T-cell receptor Vß profiles of lymphoblasts induced by these metal ions showed individual patterns, and there was no difference between healthy and allergic groups. However, the fraction of CD4+/Vß2+ cells correlated significantly with the proliferation intensity induced by Hg2+ in patients with a verified Hg allergy but not in non-allergic controls. Interestingly, such a correlation was not seen with CD8+/Nß2+ cells. This indicates that Hg2+ does not function as a superantigen, since classical superantigens also stimulate CD8+ lymphocytes. When Ni2+ was used as antigen we found significantly higher IL-10 production in allergic than in non-allergic subjects, despite no significant difference in proliferation intensity between these two groups.In conclusion, the LTT test is useful for the diagnosis of allergy to bacampicillin. Regarding Au, Pd and Ni the LIT has low validity and can only be used to discriminate groups of allergic from non-allergic individuals. LTT with Hg2+ and Ni2+ is not useful for the diagnosis of allergy to these metals since a high fraction of non-allergic individuals show positive results, irrespective of the test protocol used. This thesis calls for further studies on the usefulness of in vitro IL-10 production for the diagnosis of Ni allergy as well as on the specificity of in vitro induced CD4+N~2+ lymphoblasts from Hg allergic subjects.
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| 34. |
- Cedergren, Marie, 1963-
(författare)
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Epidemiological studies of congenital heart defects in the Southeast region of Sweden
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the most recent analysis of Swedish data on congenital malformations, it appeared that in the county of Östergötland, the prevalence of infants with a diagnosed congenital malformation was higher than in the rest of the country. This observation initiated an effort to make a more complete identification of all infants born with a congenital malformation in that county and to compare it with the other two counties in the Southeast region of Sweden (Jönköping and Kalmar), utilising all the relevant Swedish medical health registers available. A total of 10,171 infants with a congenital malformation of any type were identified in the region: 4,698 infants in Östergötland county (6.2%), and 5,473 in the reference counties (5.4%). A 15% excess malformation risk in Östergötland compared with the two reference counties. Various validations of the register data were undertaken and different types of error were detected. Limb reduction defects seemed to occur more often in Östergötland county and there was an increased risk of cardiovascular malformations in Östergötland county (22%).The next step comprised an exploration of putative risk factors for cardiac defects in the area. Maternal body mass index (BMI) >29 was found to be a significant risk factor for cardiac defects. Maternal diabetes mellitus and maternal use of antiepileptics were associated with an increased risk of cardiac defects in the offspring.To explore if the pregnant women in Östergötland county differed from the women in the reference counties, a comparative analysis of potential risk factors was performed. The only single putative risk factor that could contribute to the excess risk of cardiac defects in Östergötland county was matemal residency in a rural district. Notably, nearly all the potential risk factors studied i.e. spontaneous abortions, involuntary childlessness, maternal disease, high maternal body mass index, matemal medical during use and alcohol use in early pregnancy, parental employment and paternal age were stronger in Östergötland county compared to the reference area. A conceivable explantation is that one or more unidentified factors could activate prevalent and weak teratogenic risk factors for cardiac defects.Drinking water could be such a factor. By using a geographical infmmation system (GIS) it was possible to obtain individual data on drinking water characteristics. An increased tisk of a congenital cardiac defect seemed to be associated with the chlorination procedure, in particular the use of chlorine dioxide, and with increasing total trihalomethane concentration.
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| 35. |
- Christensson, Lennart, 1952-
(författare)
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Malnutrition in elderly people in need of municipal care : assessment and intervention
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to describe nutritional status in elderly people at the time of entering municipal care, to evaluate nutritional assessment techniques and to investigate the effect of a nutritional care plan. Furthermore the aim was to investigate the staffs' attitudes towards nutritional nursing care. A total of 261 residents, mean age 84 years (range 65-103 years), admitted to a community resident home in a municipality in the south of Sweden were included. At the same municipalities, 151 nursing staff responded to an attitude scale on two occasions with one year between.During the first or second week after admission nutritional status was assessed using a combination of anthropometry and serum protein measurements as the criterion to define protein- energy malnutrition (PEM). This combination constituted the standard criterion when validity of the Subjective Global Assessment (SGA) and the Mini Nutritional Assessment (MNA) were evaluated. In 40 residents assessed as non-PEM on admission health problems were measured by the Nottingham Health Profile (NHP). To investigate the effect of a nutritional programme energy intake, anthropometry, serum protein measurements and functional capacity were assessed continuously during a five months period in 11 residents assessed as being PEM on admission. The nutritional programme consisted of meals based on individual energy requirements. An attitude scale was developed and used in order to measure whether the attitudes of nursing staff towards important issues within eating and nutrition changed after implementation of an educational programme.On admission, 33% of 261 elderly people were assessed as being PEM. The frequency of pressure sores or leg ulcers, psychological stress or acute disease in the previous 3 months, reduced fluid intake, deteriorated appetite, reduced mobility, need of help during meals and gastrointestinal symptoms were significant higher in residents assessed as PEM compared with residents assessed as non-PEM. Both SGA and MNA proved to be useful in detecting residents objectively assessed as PEM. NHP, measuring health problems, showed power to predict residents at risk of malnutrition. Anthropometric measurements, serum protein concentration and functional capacity increased significantly in 11 residents assessed as PEM after 3 months on the individualised care programme. Nutritional education and implementation of a nutritional programme did not change the attitudes of nursing staff towards important nutritional issues.In conclusion, at the time of entering municipal care a high frequency of residents assessed as PEM or at risk of PEM was found. The SGA and MNA were shown to be useful tools in detecting resident in need of nutritional attention. For early detection of residents at risk of malnutrition, measurement of health problems added important information. An individualised nutritional care programme was one useful approach to the improvement of nutritional status and functional capacity in residents assessed as PEM on admission. On the whole, nursing staff responded with positive attitudes towards nutritional nursing care. Nutritional education and implementation of a nutritional programme did not significantly change their attitudes.
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| 36. |
- Crafoord, Sven, 1950-
(författare)
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Experimental transplantation of retinal and iris pigment epithelial cells into the subretinal space
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A dysfunction of the retinal pigment epithelium (RPE) is the main cause for the development of age-related macular degeneration (ARMD) and visual loss in elderly people. For about 10 years experimental and clinical attempts to transplant RPE cells have been performed. The aims of this study were to elucidate the long term results of RPE allografts, to develop an atraumatic transplantation technique, and to explore the cellular response to RPE allografts, melanin granules, and autologous IPE cells.Surgery was performed on rabbits with a follow-up period of up to six months. After a pars plan vitrectomy, a subretinal bleb was created into which a suspension of RPE/IPE donor cells or melanin granules was injected. Pigmented RPE donor cells or preparations of melanin granules were implanted subretinally in albino rabbits. Pigmented rabbits were used in IPE transplantation. The eyes were monitored with ophthalmoscopy, fundus photography, light microscopy, electron microscopy and immunohistochemistry.Transplantation of suspensions of fresh pigmented RPE cells to the subretinal space in rabbits is feasible and induces virtually no complications when an atraumatic surgical procedure is used. The allograft forms a monolayer in conjunction with the native RPE and persists almost intact up to three months. At six months after transplantation, there was a cellular response exhibiting multilayers of cells, such as RPE and macrophages. Damage to adjacent photoreceptors in combination with melanin granules in the subretinal space indicates graft failure. No infiltration of lymphocytes was seen. Whether the cellular response was due to immunological or non-immunological mechanisms could not be determined from this experiment.Cyclosporine (CsA) could not prevent disintegration of the RPE transplant and graft failure. CsA was not capable of promoting graft survival as compared to the controls. The transplant seems to be disrupted either by immunological mechanisms that are not inhibited by CsA, or by non-immunologic events.Implantation of melanin granules to the subretinal space of albino rabbits induces a considerable phagocytic cellular response involving the host’s RPE, macrophages and glial cells. The migration of pigment-laden cells into the neural retina was frequently associated with focal photoreceptor damage. The cellular response was identical to that ensuing RPE cell transplantation. These findings support the concept that non-immunological events have a considerable influence on the outcome.In order to evaluate the impact of non-immunological mechanisms, a technique of transplanting fresh autologous IPE cells to the subretinal space of the same eye was developed. Grafted IPE cells were seen to survive for six months. There was a remodeling of the compound cellular layers in the subretinal space over time where grafted IPE cells joined the native RPE cells. The cellular response that developed exhibited macrophages, but no lymphocytes, and was in this respect similar to that observed following RPE transplantation.In RPE allografts, the photoreceptors appeared normal on light microscopy at three months, but at six months, the photoreceptors overlying the transplants generally exhibited pathological changes. In autologous IPE grafts, on the other hand, the photoreceptors displayed normal outer segment length and outer nuclear layer on top of grafted IPE cells. Focally, multilayers of both grafted IPE and RPE cells, together with macrophages, induce damage to adjacent photoreceptors as observed at 6 months. Cellular multilayers in the subretinal space, irrespective of genesis, are likely to have adverse effects on photoreceptors. The experiments using autologous IPE grafts show that non-immunogenic mechanisms have a decisive impact on the outcome of the transplant in the subretinal space.
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| 37. |
- Dahlfors, Gunilla
(författare)
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Action and interaction of growth factors and regulatory molecules in vascular cells : With special reference to the IGF-I-system
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vascular function is greatly influenced by growth factors and regulatory molecules that can interact with each other in a complex pattern in the vascular wall. In this thesis we studied how different substances of special interest in the pathogenesis of vascular disease interact and regulate each other's expressions in endothelial cells and vascular smooth muscle cells (VSMCs).In VSMCs, angiotensin II was shown to delay PDGF-BB induced cell growth. This transient inhibitory effect of angiotensin II was mediated by the AT1-receptor, did not involve autocrine action of transforming growth factor-ß1 (TGF-ß1) and acted at a site downstream of PDGF-ß receptor phosphorylation.The interaction of the insulin-like growth factor-system (IGF-system) with various growth factors, glucose and nitric oxide (NO) was studied in vascular cells. Vascular endothelial growth factor (VEGF) and transforming growth factor-ß1 (TGF-ß1) regulated the expression of insulin-like growth factor-binding proteins (IGFBPs) in large vessel endothelial cells in a way that might cause an increased bioavailability of IGF-I locally in the subendothelial space. Angiotensin II, IGF-I and insulin did not affect IGFBP expression in these cells. The expression of IGFBPs was studied for the first time in human micro vessel endothelial cells. No effect of high glucose treatment on IGFBP expression was seen in either large vessel endothelial cells or microvessel endothelial cells. A possible interaction between NO and the IGF-system was studied in VSMCs. IGF-I did not have any significant effect on NO production in VSMCs and neither exogenous nor endogenous NO had any effect on IGFBP expression.In conclusion, we found that angiotensin II interacts with PDGF-BB in the regulation of VSMC growth. The IGF-system is regulated by VEGF and TGF-ß1 in endothelial cells while no effect of angiotensin II, IGF-I, insulin or high glucose was seen. We found no evidence for interaction of NO and the IGF-system in VSMCs.
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| 38. |
- Dahlin, Lars-Göran, 1956-
(författare)
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Perioperative myocardial infarction in cardiac surgery : a diagnostic dilemma
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Perioperative myocardial infarction remains a major cause of morbidity and mortality after cardiac surgery. In spite of this there is no consensus regarding diagnostic criteria and consequently the reported incidence varies widely. In this thesis risk factors for PMI and outcome after PMI were studied in a retrospective case control study on 42 patients fulfilling strict criteria for PM! collected from a cohort of 1147 adult cardiac surgical patients. Traditional diagnostic criteria for PMI, release characteristics of biochemical markers for myocardial injury and VCG were evaluated in a prospective study on 302 consecutive patients undergoing isolated frrst time CABG. PM! was found to be a problem mainly associated with surgery for ischaemic heart disease. Unstable angina and unfavourable conditions for revascularisation were found to be the most important risk factors for PMI. Patients with PM! had an impaired short-term and mid-term outcome compared with controls. In the prospective study a sustained elevation of troponin-T was used as a marker for permanent myocardial damage. It was demonstrated that Q-wave criteria, previously accepted as the gold standard for diagnosis of PM!, correlated poorly with biochemical markers of myocardial injury and clinical outcome. One fourth of the patients with new Q-waves after CABG had no evidence of permanent myocardial injury. The use of biochemical markers for early diagnosis of myocardial injury is interfered by unspecific release unrelated to permanent myocardial damage. However, little is known about the magnitude of this "diagnostic noise". To address this issue a subgroup with no or minimal permanent myocardial damage was identified by use of the unique release characteristics of troponin-T. The time frame of unspecific release and the plasma levels of CKMB and troponin-T caused by unspecific release were assessed. A substantial early release of both CKMB and troponin-T nnrelated to permanent myocardial injury was found. As the unspecific release can be expected to differ depending on type of cardiac intervention this type of knowledge may prevent inappropriate comparisons. Repeated early sampling for CKMB provided additional information of value for early identification of patients who would later show sustained elevation of troponin-T. VCG was found to correlate better with sustained levels oftroponin-T and clinical outcome than scalar ECG. To conclude, diagnostic pitfalls associated with both ECG and enzymatic diagnosis of PM! were addressed and novel approaches to improve detection of permanent myocardial damage are suggested.
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| 39. |
- Darelid, Johan, 1950-
(författare)
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Epidemiology and long term control of nosocomial legionnaires' disease
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The first nosocomial legionella outbreak in a Scandinavian general district hospital was identified in an epidemiological investigation of a cluster of pneumonia cases in Värnamo in 1991. During 3 months, 28 patients and 3 staff fell ill and 3 died. Legionella pneumophila serogroup (sg) 1, was found in high counts throughout the hospital hot water system and was probably spread by aerosolisation via shower nozzles. The outbreak was arrested when the circulating hot water temperature was raised from <45°C to >55°C.The nosocomial infections proved to be part of a wider legionella outbreak and 10 cases contracted outside the hospital were also detected. Legionellae were cultured from 7 of 15 community buildings and 31% (109/354) of subjects living in the Värnamo area had an elevated titre (≥6) to L. pneumophila sg 1 in 1991, indicating a temporary spread of legionella in the community. Subclinical infection was demonstrated and it was estimated that only 10% of all infections had been clinically identified. Nosocomial legionnaires' disease should alert physicians to possible legionella transmission in the community.In 21 patients from the nosocomial outbreak, the median L. pneumophila sg 1 antibody titre fell from 1:256 to 1:16 in 3 years. After 10 years, the titre level in this clinical cohort had reached the same level as observed in the background population 5 years earlier. Current international serological criteria (a fourfold or greater rise in antibody titre to ≥1:128) identified only 40% (21/52) of pneumonia cases caused by L. pneumophila sg 1 in a Swedish population in 1991-2001. When the antibody response was related to the antibody titre in local residents, the sensitivity rose to 87% (45/52).Keeping the circulating hospital hot water temperature above 55°C, and vigilant clinical surveillance of nosocomial pneumonia as a method for control of nosocomial legionnaires' disease was evaluated after 10 years of practice. Infection with L. pneumophila sg 1 was diagnosed in 4 out of 366 (1.1 %) patients treated for nosocomial pneumonia, representing 1 case per 26,000 admissions. All patients were cured without complications. L. pneumophila sg 1 was isolated in 30 of 251 (12%) cultured hospital water samples during the monitoring period. It was concluded that this approach was safe and effective for long term control of nosocomial legionnaires' disease in a primary referral hospital.The hospital hot water system was found to be colonised with a single genotype of L. pneumophila sg 1 over a 12-year period. The same genotype, identified using amplified fragment length polymorphism (AFLP) analysis, was also demonstrated in 18/20 (90%) community isolates. The phenotypic variation was confined to the monoclonal antibody subtypes Benidorm and Bellingham. The hospital genotype was identified in 2 out of 6 Swedish hospitals, both located within 100 km of Värnamo. Obviously, an entire municipal water network may constitute a distinct ecological niche for a single legionella strain. Certain clones also seem to be widely spread in the environment. This implies that results from molecular subtyping must be interpreted cautiously in epidemiological investigations of legionnaires' disease.
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| 40. |
- Dobrydnjov, Igor, 1963-
(författare)
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Perioperative effects of systemic or spinal clonidine as adjuvant during spinal anaesthesia
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim of study: To evaluate the effects of different doses of clonidine administered systemically or spinally in combination with local anaesthetics on sensory and motor block intraoperatively, on pain relief postoperatively, and on the incidence of postoperative alcohol withdrawal syndrome (AWS) in alcohol abusers.Patients and methods: A total 285 patients were included in five studies. In two studies, oral clonidine (150 and 300 µg) or intrathecal clonidine (100 and 150 µg) was combined with local anaesthetics to evaluate the quality of sensory and motor block and postoperative analgesia. In a third study, the ant-idelirious effect of a single dose of clonidine (150 µg) given orally or intrathecally before operation was studied in 45 heavy alcohol abusers (daily ethanol intake of at least 60 g). The combination oflow doses of clonidine (15 and 30 µg) intrathecally with low dose bupivacaine was investigated during ambulatory herniorrhaphy. In a combined spinal-epidural anaesthesia study, a moderate dose of postoperative epidural clonidine (40 µg/h) was studied with or without low dose intrathecal clonidine (15µg); plain local anaesthetic was used as control. Sensory block was assessed by pin-prick, light touch, thermotest and transcutaneous electric stimulation; motor block was estimated by a modified Bromage scale. Pain intensity according to a Visual Analogue Scale (VAS) and analgesic request were recorded. AWS was assessed by the criteria of the Diagnostic and Statistical Manual of Mental Disorders.Results: Intraoperatively, high doses of oral or intrathecal clonidine added to local anaesthetics almost doubled the time of sensory and motor block, and it was possible to reduce the dose of local anaesthetics without diminishing of the quality of spinal anaesthesia. Low doses of clonidine (15 µg) in combination with a low dose of bupivacaine significantly increased the spread of analgesia (4 dermatomes) without significantly prolonging the motor block. The same dose of clonidine combined with a high dose of bupivacaine significantly prolonged the sensory- and motor block by 36% and 18%, respectively Postoperatively, both oral and intrathecal clonidine prolonged time to first analgesic request. V AS score was acceptably low in all study groups. However, a high dose (150 µg) of intrathecal clonidine reduced postoperative 24-hour morphine consumption by 40% compared with control, while morphine-sparing was 55% when a low dose (15 µg) of intrathecal clonidine was combined with epidural clonidine. In ambulatory practice, low doses of intrathecal clonidine decreased analgesic requirements at home for up to 24 h after operation. In comparison with diazepam premedication, clonidine 150 µg, intrathecally or orally, reduced the incidence and degree of postoperative AWS in alcohol-dependent men (from 80 to 10%). The major side-effects of clonidine were hypotension and sedation, especially after oral administration. This hypotensive effect was also found after epidural clonidine infusion.Conclusion: Clonidine, as an adjuvant to local anaesthetics, provided a higher quality of anaesthesia and postoperative analgesia and prevented postoperative alcohol withdrawal syndrome in alcohol abusers. Side effects such as hypotension and pronounced sedation postoperatively should be kept in mind if high doses of clonidine are used.
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