| 11. |
- Johnson, Anders
(författare)
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Breathe without pain : Clinical and experimental studies in patients and volunteers with special reference to ventilatory regilation
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The major aims were, first, to study the advantages and disadvantages of intrathecal analgesia with bupivacaine and morphine with special reference to ventilation and pain relief and, second, to develop a method for studies of the ventilatory response to carbon dioxide and hypoxaemia in volunteers and in patients with varying degrees of ventilation-perfusion ratios.341 elderly patients undergoing major hip surgery perfonned under intrathecal analgesia or general anaesthesia and 31 young and healthy volunteers participated in this work. There were fewer complications and a shorter postoperative hospital stay in patients undergoing surgery under intrathecal analgesia with 0.3 mg morphine added to 20-22.5 mg bupivacaine without glucose compared to the general anaesthesia group as evaluated with the aid of case records. Postoperative pain after intrathecal morphine was evaluated by systemic morphine consumption and a visual analogue scale and was found to be of good quality for at least 40 h in the majority of the patients. Postoperative naloxone infusion rate was lowered stepwise between patient groups receiving intrathecal morphine. The dose 1 pg/kglh IV for 12 h and 0.25 pg/kg/h IV for the next 12 h had no influence on pain relief obtained by the intrathecal morphine.A non-rebreathing cireuit was designed and evaluated in volunteers and patients. The apparatus had no influence on ventilation of air over time, the results could be reproduced and the method was found to be suitable and safe for patients with varying ventilation-perfusion ratios. The ventilatory response to C02 was measured after 1.5 times the time taken to reach a new steady-state in FIITC02 after stimulation with 6% C02. The ventilatory response to hypoxaemia was measured when S02 had declined from normal values to 85%. The responses were evaluated before operation and 8 and 24 h after intrathecal injection in three patient groups: intrathecal analgesia with bupivacaine, with bupivacaine-morphine and with bupivacaine-morphine plus an IV infusion of naloxone. Intrathecal morphine had, on the whole, no effect on the ventilatorytesponses. However, additional systemic morphine or sedatives attenuated the responses. Naloxone infusion was judged to counteract ventilatory depression. The response to hypoxaemia was poor or absent in 1/3 of the elderly before operation,In conclusion, intrathecal analgesia with a mixture of bupivacaine and morphine offers excellent operative conditions in major hip surgery and a favourable postoperative course without pain for the elderly patient. Postoperative care of these elderly patients for at least 24 h is recommended and experienced personnel should continuously evaluate patients' status for detection of signs of ventilatory depression. The staff should have the knowledge and the facilities to treat ventilatory depression. Naloxone infusion can well be used as prophylaxis against ventilatory depression. Oxygen therapy is also recommended in these elderly patients both during and after operation until normal or near normal oxygenation, without oxygen therapy, is proven present.
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| 12. |
- Leandersson, Per, 1958-
(författare)
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Mineral fibers, cigarette smoke, and oxidative DNA damage : An experimental study
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study concerns the ability of mineral fibers and cigarette smoke to generate reactive oxygen metabolites and to cause damage to DNA. The generation of hydroxyl radicals (OH") was demonstrated by using the DNA base, deoxyguanosine (dG) as a trapping agent for OH" and determining its hydroxylation to 8-hydroxydeoxyguanosine (80HdG), and oxidative DNA damage was assessed as formation of 80HdG in isolated DNA or in DNA of human lung cells in culture. Both asbestos (chrysotile) and manmade mineral fibers (~)were found to generate OH" and damage DNA in aqueous buffer solutions, andmore OH· was generated by the iron-containing rock and slag wools than by glass wool and ceramic fibers. The OH• generation by rock wool was decreased by treatment with heat, oxygen or desferrioxamine, indicating that chemical characteristics including iron on the fiber surface were important determinants of the OH" formation. A variety of natural mineral fibers (asbestos, erionite, and wollastonite) and MMMF (rock wool, glass wool, and ceramic fibers) were found to stimulate polymorphonuclear leukocytes (PMNL) togenerate OH" in the presence of exogenously added iron, and amosite, crocidolite, antophyllite, erionite, and wollastonite caused OH" formation also in the absence of exogenously added iron. Cigarette smoke potentiated the damaging action of rock wool onisolated DNA, suggesting that iron-containing fibers might catalyze O:H" formation from hydrogen peroxide generated in the smoke. Cigarette smoke-induced damage to isolated DNA was inhibited by tyrosinase and catalase, indicating that polyphenols in the smoke,e.g. hydroquinone and catechol, were important for the hydrogen peroxide generation. Cigarette smoke was also found to cause oxidative DNA damage and DNA strand break formation in cultured human lung cells by mechanisms involving OH" attack on the DNAmolecule and endonuclease activation. Moreover, cigarette tar was demonstrated to promote P:MNL-mediated DNA strand-break formation in human lung cells, and tar loaded with iron was more damaging than regular tar.These fmdings indicate that mineral fibers, by producing OH· themselves and by stimulating PMNL to generate OH· in the presence of iron, may cause oxidative DNA damage under experimental conditions. They also indicate that cigarette smoke may cause DNA base hydroxylation and DNA strand-break formation in human lung cells via mechanisms involving OH", and that iron is important for the OH•-formation. Altogether, the findings point to the possibility that mineral fibers may promote OH" generation by cigarette smoke and inflammatory cells and so increase the risk of DNA damage in human lung cells.
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| 13. |
- Lindberg, Eva
(författare)
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Crohn's disease : Studies on epidemiology, twins, aetiological factors and clinical course with special reference to smoking
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In an epidemiological study of the incidence of Crohn's disease in Orebro county during the 25-year period 1963-1987, the mean annual incidence was 6.1/105 inhabitants. During the first five year period the mean incidence was 4.3 but during the following four quinquennia the incidence was stable at around 6.6/105 inhabitants. The point prevalence at 31/12 1987 was 146/105, with male to female ratio of 1:1.15. The mean age at diagnosis increased from 23 to 32 years. No cohort more prone to develop the disease was found. Of the 246 incidence cases 5 patients had died of Crohn's disease.The genetic influence was analysed in 18 monozygotic and 26 dizygotic twin palrs with Crohn's disease. Eight of the monozygotic palrs were concordant for the disease but only one of the dizygotic pairs. The proband concordance rate was 58.3% for monozygotic twins and the heritability of liability (r) 1.0. The corresponding figures for dizygotic twins were 3.9% and 0.47. When comparing with ulcerative colitis the heritability was found to be significantly stronger in Crohn's disease.A case-control study of smoking habits in 144 patients and 259 matched population controls showed that smoking doubled the risk of aquiring Crohn's disease. In former smokers a non-significant increased risk was observed.The effects of smoking on the localization and course of Crohn's disease was evaluated in 231 patients. Patients with high life time tobacco exposure (>150 cig.years) had small bowel disease more often than patients with low life time exposure. Heavy smokers(> 10 cig./day) had a slightly increased risk to be operated at least once, odds ratios after 5 and 10 years of follow up for heavy smokers compared to never smokersbeing 1.14 and 1.24 respectively. The risk for heavy smokers to be operated twice or more was even higher after 10 years offollow up, the odds ratio being 1.79. The accumulated number of fistulae and/or abscesses was higher in smokers than never smokers.Twenty-six monozygotic twin pairs with inflammatory bowel disease and 52 healthy controls were investigated for serum antibodies (IgA, IgG, IgM) against ovalbuntin, betalactoglobulin, gliadin, whole yeast (Saccharomyces cerevisiae) and mannan. Twins that had developed Crohn's disease displayed higher titers of all three antibodies towards mannan, and also higher IgA towards yeast. Their healthy twin hadhigher IgA to mannan and yeast. These results suggest that yeast cell wall material for instance mannan or some antigen rich in mannose and cross reacting with mannan might play an aetiological role in Crohn's disease.Conclusion: The incidence of Crohn's disease has been stable during the last 20 years. The genetic influence is important. Smoking increases the risk of aquiring Crohn's disease and heavy smokers have a worse outcome of the disease. Patients with high life time tobacco exposure more often have small bowel disease. Mannan or agents cross-reacting with mannan may play a role in the pathogenesis of the disease. However, not even similar smoking and dietary (as ntirrored by dietary antibodies) habits in identical twins are sufficient to cause disease. Additional factors are needed.
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| 14. |
- Lindgren, Richard
(författare)
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Climacteric Symptoms and Hormonal Treatment with special reference to Sequential Transdermal Therapy
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Changes during female menopause include increased prevalence of vasomotor symptoms, vaginal symptoms, changes in sexlife and metabolic changes with increased risk of osteoporosis and cardiovascular disease. These changes are to some extent counteracted by estrogen replacement therapy.The aim was to study the prevalence of vasomotor symptoms, sexlife and estrogen replacement therapy in a postmenopausal population. The aim was also to study the effects of a new sequential transdermal estrogen/gestagen therapy on endometrium, bleeding pattern, Quality of Life and on plasma lipids and lipoproteins.Two epidemiological studies with postal questionnaires were answered by 1469 and 1867 women, respectively. Their ages were between 55 and 65 years. The prevalence of postmenopausal vasomotor symptoms was high. Eighteen percent of the women still had moderate to severe vasomotor symptoms even 15 years after menopause. There was a great discrepancy between the prevalence of vasomotor symptoms and hormonal replecement use. Many women discontinued treatment within the first year of treatment. The most common reason for discontinuation was lack of symptoms when treatment was ceased (25% ), followed by "fear of side-effects of the treatment" in 20% of the women.Most women had a regular sexlife even 15 years after menopause and the most common reason for sexual inactivity was lack of partner.One hundred and ten women with climacteric symptoms received a new sequential transdermal estradiol/norethisterone acetate therapy in a multi-centre study for one year. The therapy resulted in secretory endometrium in most women (65%) and only one woman developed hyperplasia after one year. The bleeding pattern for 1195 cycles were studied and 89% of the cycles -were regular or amenorrboic. The treatment resulted in improvement of Quality of Life after 9 months of treatment among 84% of the 110 studied women. The women experienced less anxiety and depression and increased vitality and self-control according to the Psychological Well Being Index. They also experienced better sleep according to the Sleeping Scale. The women also indicated less vasomotor and somatic symptoms and less anxiety and depression according to The Women Health Questionnaire. This test also showed improvements in sex-life, emotions and cognitive symptoms among the women.Twenty-five women at one centre were also studied concerning the effect of the treatment on plasma lipids and lipoproteins. The total cholesterol and LDL-cholesterol was reduced after three years of treatment. The triglycerides and HDL cholesterol was not significantly changed after 3 years of treatment.
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| 15. |
- Lundquist, Per
(författare)
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Determination of cyanide and thiocyanate in humans
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cyanide exposure from several sources may cause chronic diseases or acute lethal intoxication in humans. Accurate and specific methods for determination of cyanide and its metabolite thiocyanate are therefore needed for clinical and epidemiological purposes. An improved method for determination of thiocyanate in serum and urine was developed by adsorption of thiocyanate on a weakly basic anion-exchange resin by a chaotropic effect, followed by colorimetrical determination by a modified Konig reaction. Dietary intake of cyanide and sulfur was estimated by determination of urinary thiocyanate and inorganic sulfate in a Mozambican population affected by the paralytic disease konzo. Konzo was found to be associated with a high cyanide and low sulfur intake from a diet dominated by cassava roots that were consumed without removal of the naturally occurring cyanogen compounds. A low intake of sulfur containing proteins was supposed to enhance toxic effects of cyanide by reducing cyanide to thiocyanate conversion.For determination of blood cyanide in field studies an analytical method that enabled transport of samples was developed. Cyanide was stabilized in blood by adding silver ions and after distillation determined by the Konig reaction. A 30-fold increase in sensitivity was obtained by fluorometric determination of the Konig chromogen, which enabled determination of physiological blood cyanide levels 0.117 ± 0.038 J..Ullol/L (mean± SD), and blood cyanide after smoking a cigarette 0.424 ± 0.173 f.tmol/L. A rapid method for determination of toxic blood cyanide levels could be developed by separating the cyanide containing erythrocytes from thiocyanate containing plasma by washing with saline and thereafter protein precipitation followed by direct spectrophotometric determination of the König chromogen.Measurement of hydrogen cyanide in breath showed no correlation with blood levels of cyanide. Experiments revealed that most of the hydrogen cyanide found in breath from normal human beings originates from oxidation of thiocyanate by salivary peroxidase in the oropharynx.In a study of fire casualties 9 out of 18 victims had toxic blood cyanide levels (> 40 J..Ullol/L) and one had a blood cyanide level of 101 J..UllOI/L but a nontoxic blood carboxyhemoglobin, which suggests a lethal effect of cyanide exposure. Blood cyanide levels in two suicidal intoxications were found to be 105 and 139 J..UllOl/L. A lethal outcome in one of the cases that received insufficient antidotal treatment indicates that immediate laboratory verification of cyanide intoxication may be life-saving.
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| 16. |
- Malmqvist, Lars-Åke, 1951-
(författare)
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Sympathetic neural blockade during regional analgesia : Clinical investigations in man
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Different opinions exist concerning the extent and intensi-ty of the concomitant sympathetic block during regional blockade, and how to test the completeness of the sympathetic blockade. Studies were performed on 21 volunteers and 162 patients scheduled for surgery of the urogenital area or surgery for varicose v-eins, and chronic pain patients. The regional blockades used were intrathecal, extradural or stellate ganglion blockade. The skin resistance response method (SRR) was used for recording sympathetic nervous activity in all studies. Laser Doppler flowmetry and skin temperature recordings were used during stellate ganglion blockade, to evaluate changes in skin blood flow and skin temperature. Changes in cardiac output were evaluated by the dye dilution method or thoracic impedance cardiography. Vagal activity was evaluated by recording changes in RR intervals from the electrocardiogram (ECG). Afferent blockade was assessed using the pin-prick method and also somatosensory evoked potentials (SEPs). A partial sympathetic blockade was seen during intrathecal, extradural and stellate ganglion blockade in most cases according to SRR-recordings. The haemodynamic parameters, cardiac output (CO), stroke volume (SV) and systemic vascular resistance (SVR) were well preserved, provided an i. v. pre-load infusion was given before and during onset of intrathecal blockade. There was no evidence of parasympathetic dominance causing hypotension during intrathecal blockade. The SEPs and SRRs were blocked in a similar way. For reliable assessment of sympathetic nerve block, it is necessary to evaluate the effect on both the sudomotor and vasoconstrictor fibres.
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| 17. |
- Messner, Karola, 1956-
(författare)
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Meniscectomy, meniscal repair, and prosthetic substitution : Clinical and experimental investigations
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study comprising 7 papers is concerned with different treatment of meniscal injuries. The aim was to analyse today's clinical methods and the possibility for prosthetic substitution in the future. Open peripheral meniscal repair was compared with partial arthroscopic meniscectomy in a 7·year follow-up evaluation of 130 patients. The reoperation rate was about 25% after both alternatives. The patients' willingness to undergo repair repair, however, was low because of the long rehabilitation period.Meniscal repair led to- greater improvement in function than did partial meniscectomy and was associated with a lesser degree of osteoarthritis. Knees with anterior cruciate ligament deficiency followed a clinical course-dominated by the instability.Meniscal substitution with a prosthesis ofpolyurethane·coated Dacron or Teflon or uncoated Teflon was studied in 114 rabbits. Despite their large size and mechanics different from those of a nonnal rabbit meniscus the Dacron prostheses became incorporated, with fibrous tissue ingrowth. Knees furnished with such a prosthesis developed less osteoartbritis on the tibial surface than did meniscectomized knees, but synovitis and osteophyte fonnation were common. Knees subjected to sham operation or meniscal inciSion showed no such changes. Knees furnished with a modified prosthesis of appropriate size and with improved material mechauics developed no naked·eye cartilage changes, but osteophyte fonnation, cartilage softening, and synovitis continued to appear. Despite better in·vitro mechanics, uncoated prostheses gave inferior results owing to changes in shape and to debris fonnation during the implantation period. In A CL-deficient knees the benefits of a prosthesis were seen only during the first 6 weeks, when the prosthesis had been implanted immediately after meniscectomy. After 3 months differences in treatment could no longer be distinguished owing to the overall effects of ACL resection.
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| 18. |
- Moidu, Khalid, 1950-
(författare)
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Computer-based support for maternal and child care at primary health centres
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Health infonnation systems are reported to be weak and inadequate in supporting public health programs, since at the primary health centre, which is the level of first contact, the information infrastructure is weak. This thesis reports a health systems research effort to strengthen the infonnation infrastructure, specifically to develop an application software to support the delivery of maternal and child care at the primary health centre. Technical advances have made micro-computers affordable, which is directly due to the trend toward lower prices. However, there is still a lack of flexible low cost software for large scale implementation. This health systems research used methodologies based on empirical findings combined with the engineering process of design and development. Based on the shared characteristics of the sites and the human component requirements, an application software was developed and tested.The investigation had three distinct stages, the first of which was a prerequisites analysis to assess the human issues of acceptance and attitudes using a questionnaire based study. The results demonstrated that responding physicians were interested in using computers, but an information gap existed. Respondents with somecomputer experience and prior information accepted the potential of the computer as a decision support tool, but those without experience had reservations (I). The first stage also included a literature review to identify the values of infonnation justifying computer role rather than manual methods used in a primary health centte (II). The second stage was a multi~centre systems analysis study using questionnaires and site visits to identify the common base for development of an application software. Analysis by contingency tables showed diversity in socio-organizational factors between the sites (III), while commonality was observed in the data collection records and this was confinned by the site study. The site study further identified that a core data set is shared by all levels of administration and care providers in delivery of a health programme. Development of a common application software requires identification of the core data set (IV). The third stage was to design and develop the software. For this the Essential Data Set for the selected domain of Maternal Health Services was defined by means of infological modelling, A software prototype was developed, and using rettospective data entry from a Swedish maternal health centre records the acceptability of the data set and applicability of the software were tested (V). The software developed, which was independent of organizational behaviour, provided us with a package that could be used by different health organizations. It was implemented differently by different organizations using their own economic resources. The results demonstrated that the software provided the foundation for microplanning, and that the management at a site was able to identify the needs and lacunae. At another site the target group for family planning motivation was fine tuned to a subset, and the action resulted in 25% of the subset accepting a permanent method. The database will also be an asset in quality assurance by ensuring continuity in care and the resultant large database based on a prospective common data collection protocol will be a base for health outcomes research. A further observation is the economic loss due to dropouts from the immunization programme. The approximated cost per fully immunized child is estimated at US$ 15. As a result of dropouts from the cohort the cost rose to US$ 54 per fully immunized child, but with computer supported follow-up the dropouts decreased and the cost fell to US$ 22 per fully immunized child (VI). The economic benefits are proof that such systems are not an expenditure but are instead an investment.
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| 19. |
- Orhagen, Tina
(författare)
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Working with families in schizophrenic disorders : the practice of psychoeducational intervention
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psychoeducational intervention including educational courses for relatives and individual family sessions was carried out with relatives of patients suffering from schizophrenic disorders. Relatives' Expressed Emotion (BE), amount of illness-related knowledge, burden of care, and satisfaction with the intervention were assessed.Relatives' measures of BE (critical remarks, hostility, emotional overinvolvement) and the general BE index decreased significantly after the complete intervention, comprising educational courses for relatives from different families and, for a period of two years, individual family sessions with the participation of the patient. The number of relatives scoring high on the BE index, was significantly reduced after the initial educational courses. The interrater reliability of BE measures, assessed with the Swedish version of the Camberwell Family interview schedule and calculated on data from audiotaped interviews, was generally high.The amount of illness-related knowledge increased significantly after the multifamily educational courses. Gain in knowledge and high satisfaction with the intervention were associated with decrease of criticism towards the ill family member, and with relief of relatives' subjective burden. The relatives expressed an appreciative evaluation of the intervention and indicated the socializing and sharing of experiences with other relatives as a most valuable component.In the face of relatives' need for information about the illness, the diagnostic process of schizophrenia was studied. Retrospective analyses of case-records from 84 in-patients showed that schizophrenic disorders were ascertained as case-record diagnoses on average six years after the first contact with the mental health service. The findings suggest a propensity to include prolonged course and severe impairment of social functioning in the clinical concept of schizophrenia.
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| 20. |
- Rosenberg, Per
(författare)
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On the prognosis and treatment of early stage endometrial carcinoma : Studies with special reference to uterine papillary serous carcinoma
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The prognosis and therapy in the subgroup of endometrial malignancies called Uterine Papillary Serous Carcinoma (UPSC) was investigated. This entity constitutes about 6-8 % of all endometrial carcinomas clinical stage I but, as has been shown here, accounts for one third of the cancer mortality in the early stages of endometrial carcinoma.-The prognostic significance of nuclear atypia, FIGO grade and age was determined in patients with clinical stage 1-11 Uterine Papillary Serous Carcinoma.-DNA-index and S-phase fraction, determined by flow cytometry on formalin-fixed, paraffin-embedded endometrial curettage material was evaluated in relation to nuclear atypia, FIGO grade and age in early stage endometrial carcinoma.-A new method of minimizing the dilution of non-epithelial cells in the malignant curettage material when performing flow cytometry was developed.-The survival and pattern of metastasis in a population-based patient material was investigated -The effects on survival of a new aggressive treatment regimen was assessed.The results show that: Patients with uterine papillary serous carcinoma have a much worse prognosis than do patients with ordinary endometrial carcinoma.DNA ploidy and S-phaseratederived from flow cytometryperformed on disintegrated, previously paraffinembedded, endometrial curettings are important prognostic factors.It is possible to exclude contaminating non-epithelial cells from the DNA analysis by the use of an anticytokeratin antibody, Patients with uterine papillary serous carcinoma clinical stage I have a significantly higher risk of recurrence than patients with non-UPSC. The localisation of the recurrences among the UPSC patients is more similar to that of serous papillary ovarian carcinoma than that of ordinary adenocarcinoma of the endometrium. A primary treatment ofUPSC with a more extensive surgery, adjuvant external radiation and platinum-based chemotherapy seems to improve the outcome.
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