| 11. |
- Larsson, Hans
(författare)
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Myocardial ischemia : As a risk indicator after an episode of unstable angina or non-Q-wave myocardial infarction
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The diagnostic and prognostic value of different noninvasive tests were evaluated in men below 70 years of age admitted to the coronary care unit (CCU) with unstable coronary artery disease (CAD) i.e unstableangina or non-Q-wave myocardial infarction (Ml). A symptom limited exercise test (ET) was performed before discharge in 740 patients. In subgroups 24 hour ST-recordings were performed in the CCU (n=75),before discharge (n=198) and ambulatory after one month (n=109). A second ET combined with SPECT Tl201 myocardial perfusion imaging was done after one month in 197 patients. Myocardial ischemia was defined as ST-depression > 0.1 m V or according to a model developed for interpretation of SPECTT1201 scintieraphy. All patients were followed one year. Patients with myocardial ischemia at the predischargc ET (51 %) had a significantly higher rate of death or MI (18 %) compared to those without (9 %) regardless of simultaneous pain or not. STrccordingin the acute phase or before discharge showed less often myocardial ischemia (23-18 %) than ambulatory during ordinary daily life (33 %). In the same group of patients myocardial ischemia was more often elicited by a predischarge ET (52%). The majority of patients with ST-depression at ST-recordings also showed myocardial ischemia at the predischarge ET. Myocardial ischemia at the ST-rccording beforedischarge identified a small group (18 %) of patients with a more severe prognosis- 23% rvn or death after 3 months compared to 7 % in the patients without this observation. In a logistic regression analysis ST-depression at the predischarge ST-recording was the only significant predictor of MI or death during the first three months while myocardial ischemia at the predischarge ET became the only significant indicator of long term outcome. In a comparison between the predischarge and the one month ET 83 % of patients showed the same response regarding occurrence of ST -depression. The rate of MI or death during the first month were more common in patients with (8.3 %) than without (3.7 %) myocardial ischemia at the predischarge ET and so was the occurrence of future symptoms of severe angina. Regarding the following 11 months, myocardial ischemia at the predischarge or the one month ET had the same prognostic importance for MI, death or severe angina. SPECT Tl 201 imaging at ET improved the separation between high and low risk patients. If both SPECT Tl 201 imaging and the ECG response showed signs of ischemia (37 %) the risk of future cardiac events was markedly elevated- 17 % MI or death compared to 7 % in patients without this finding. Thus, risk stratification of men after an episode of unstable coronary artery disease can be performed already before discharge. Patients with continuing myocardial ischemia despite treatment should be considered for rcvascularisation whether or not the ischemia is associated with pain.
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| 12. |
- Larsson, Per-Göran
(författare)
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Bacterial vaginosis : Diagnosis, treatment and significance in gynaecological practice
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bacterial vaginosis (BV) is a syndrome which is characterized of a disagreeable vaginal discharge but not necessarily an increase in discharge and is present in nearly 20-30% of women attending gynaecological out-patient clinics. Some women have BV unknowingly but others suffer the disagreeable discharge as a lifelong nuisance and areconstantly visiting physicians without relief. This problem has even been regarded as an aesthetic problem and has received little attention, especially from gynaecologists. The diagnosis of BV is based on the fulfilment of three out of four clinical criteria as introduced by Amsel in 1983. Few studies have been carried out investigating whether BV is a risk factor for other gynaecological diseases such as bleeding disturbances or postoperative infections. The aim of this thesis was to investigate the role of BV in gyrtaecological diseases and to evaluate whether it is possible to make a reliable diagnosis of BV using saved smears, such as air-dried or Papanicolaou (PAP)-stained smears. This would make it possible to investigate a large material and enable retrospective investigations. Since vaginal leucocytosis has been regarded as a sign of genital infection, women with BY and leucocytosis have often been withdrawn from clinical studies. The presence of leucocytosis among women without BV was therefore also investigated to evaluate if this practice is justifiable. The diagnosis of BV using Amsel's criteria was compared with the detection of clue cells in air-dried vaginal smears or with the detection of clue cells in PAP-stained smears. Detection of clue cells in air-dried smears had a sensitivity of 96% and a specificity of 98% in diagnosing BY, and detection of clue cells in PAP-stained smears had a sensitivity of 90% and a specificity of 95%. Leucocytosis cannot be used to exelude BV as nearly 30 OJo of all women have leucocytosis regardless of whether BV is present or not and that healthy women can normally have transient leucocytosis during a menstrual cycle. The significance of BV in postoperative infections after gynaecological surgery and bleeding disorders was studied. BV was found to be a risk factor for pelvic inflammatory disease after first-trimester abortion, and postoperative infection following abdominal hysterectomy. A common complaint with a multifactorial etiology at a gynaecological out-patient department is bleeding disorder. Women with BV and with Mobiluncus were treated in a double-blind study with either metronidazole or with placebo. BV was successfully treated in 76% of the women. The bleeding disorder was regularized in all successfully treated women. Women with BV are at risk of developing a post-operative infection after first trimester abortion. One-hundred and seventy-four women with BV were treated in a doubleblind study with either metronidazole or placebo the week before the abortion. There were 12.2% post-operative infections in the placebo group compared to 3.6% in the group treated with metronidazole. The treatment thus reduced the incidence of infection by more than 3 times. Using simple clinical criteria it is possible to identify a risk group which if treated will reduce the incidence of postoperative infections after legal abortion. In Sweden with 36 000 abortions each year preoperative treatment of 10 000 women with BV will prevent 860 post-abortion PID's per year.
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| 13. |
- Ledin, Torbjörn, 1962-
(författare)
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Dynamic posturography in evaluating human equilibrium
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Equilibrium assessment by means of posturography can be performed ina dynamic fashion, meaning that the environment does not remainstable during the test. In the EquiTest dynamic posturography version, the support surface and the visual surround are movable, actively or in response to body movements. Equilibrium ability is investigated in a sensory organ1zat1on (SO) part where six different combinations of vision (normal, sway referenced and absent) and support surface conditions (stable and sway referenced) are given. Postural responses to sudden translations and tiltings of the support surface are investigated in a movement coordination (MC) part. standardized dynamic posturography was utilized to assess equilibrium performance in different groups of subjects. In twentynine elderly healthy subjects, dynamic posturography evaluated the influence of age on equilibrium parameters. A decline compared to younger age groups was f~und. Fifteen of the elde:ly s~bjects underwent physical exerc~ses two hours a week dur~ng n~ne weeks, the remaining subjects served as controls. Significant improvement attributable to the exercises was found in one out of six so conditions and two out of twelve clinical equilibrium tests. In twenty-eight subjects with polyneuropathy, impaired equilibrium was found in so and delayed reactions to sudden support surface movements -w~re found in MC. Comparing dynamic posturography with neurological measures of polyneuropathy unveiled correlations between subjective clinical scoring and latencies to forward translations in MC and to equilibrium performance in three out of six so conditions. In seven subjects with chronic toxic encephalopathy due to industrial solvent exposure, impaired equilibrium was found in four out of six so conditions, although MC was normal. In thirteen healthy subjects, acute low level alcohol ingestion caused balance disturbances in SO conditions with abs7nt visual cues. In addition to disturbances of ocular smooth pursu1t and visual suppression of the vestibuloocular reflex in elevenabstinent chronic alcoholics, deteriorated equilibrium performance was found in four so tests out of six. Postural reactions to both sudden translations and tiltings of the support surface were found to be marred, in spite of normal nerve conduction velocities. The EquiTest dynamic posturography apparatus was cont:olle~ by amenu-driven interface constructed at the department, ~n wh~ch the user may expose the subject to arbitrary movement~ ~f the.supp~rt surface and the visual surround. The effects of v1s1on, d~rect~on and amplitude on postural reactions to su~den support surface translations were evaluated. Absence of v1sual cues caused more rapid correction maneuvres, but the translation direction did ~ot influence the reactions. Postural responses reflected translat1on amplitudes.
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| 14. |
- Magnusson, Martin, 1978-
(författare)
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Experimental studies of small intestinal permeability and function in uremia
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The intestinal permeability has been investigated in experimental chronic and acute uremia in rats. The permeability and the mucosal ability to exclude larger molecules have been measured using differently sized polyethylene glycols (PEG 400 and 1000: mean weights of 400 and 1000 dalton, range 326-1162 dalton). The permeation (uptake) of the differently sized molecules has been estimated from the urinary recovery of the PEGs after oral administration of the permeability markers. The effects of two different diets (high-and low-protein) have been studied inexperimental chronic uremia and in normal rats. The renal excretion of the PEGs after intravenous administration has also been investigated in chronic uremic rats. Furthermore, the effect of experimental acute uremia on intestinal brush border peptidases, disaccharidases and mucosal morphology have been studied. Finally has the urinary recovery of PEGs been investigated in patients with renal insufficiency compared to healthy subjects.The urinary recovery of PEGs was reduced after intravenous administration in chronic uremic rats. The relative excretion of the smaller PEGs was, however, increased compared to the larger ones in the uremic rats. The opposite was found in the control rats. Intestinal permeability, measured as an increased urinary recovery after oral administration of larger PEGs, was increased in chrortic uremic rats.The overall urinary recovery of the PEG molecules was reduced in patients with renal insufficiency. However, the relative excretion of the differently sized PEGs indicated a relative increased uptake of larger molecules also in uremic patients suggesting a more permeable gut.An opposite pattern was seen in experimental acute uremic rats, reduced urinary recovery along with a relative decreased excretion of larger molecules compatible with a less permeable gut.Moreover, both in the chronic uremic and in the control rats treated with low-protein diet was a reduction of intestinal permeability seen.Increased activity of brush border peptidases was found in acute uremic rats. Minor morphological changes, shortening of the microvilli of the enterocytes in the small intestine were also observed. On the other hand, no alterations of the disaccharidases were measured.In conclusion, the change in intestinal permeability indicates a more leaky mucosal barrier in chronic uremia. Functional alterations i.e. increased peptidase activity was seen in acute uremic rats. A more leaky gut might allow potentially toxic, infectious and immunogenic substances to pass more freely over the mucosa in chronic uremia.
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| 15. |
- Massoud, Rasi Marzabadi
(författare)
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Free radicals in cellular pathology : Mechanisms behind lipofucin formation in cultured myocardial cells
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lipofuscin, or age pigment, may be defined as a yellowish-brown,autofluorescent, protein and lipid containing pigment that accumulates inthe lysosomal vacuome of a variety of post-mitotic cell types in man andanimals during aging. Lipofuscin is the end product of peroxidation,fragmentation and polymerization of proteins and lipids. Protein andlipid containing materials are regularly sequestered to the lysosomal system by means of pinocytosis, phagocytosis and autophagocytosis. Lipid peroxidation involves the production of semistable peroxides from free radical intermediates produced by direct reaction of oxygen derived reactive metabolites with unsaturated lipids. The aim of the present project was to isolate the factors thought to be involved in the formation of lipofuscin by using a cell culture model of post-mitotic myocardial cells. Specifically the role of oxidative stress, transition metals, metal chelators, oxidants, antioxidants and lysosomal enzyme inhibitors. We introduced our cell culture model system and reported briefly theeffect of oxygen stress on lipofuscin accumulation (paper 1). Our resultsindicated that the level of autofluorescence, increases in direct relationship to age in culture and ambient oxygen concentration. The rapid increase of autofluorescence materials in the cells kept under 40% oxygen is thought to be due to the high production of superoxide anion radicals. Another study (paper ll) was aimed at the catalytic effect of metals onlipofuscin formation using the transition metal iron and the metal chelatordesferrioxamine on lipofuscin formation. Lipofuscin was quantified by microspectrofluorometry of individual cells. Augmentation of iron in the culture medium markedly increased the level of lipofuscin accumulationwhile desferrioxamine had the opposite effect. Both of these effects were more pronounced at higher oxygen tension. The effect of the hydrophobic-hydrophilic, peroxyle radical trapping, chain-breaking antioxidant vitamin E and some metal chelators e.g. EDTA, DTPA and Desferal was studied (paper Ill). All of them except EDTA decreased lipofuscin accumulation. In paper IV, inhibition of proteinases and lipases were studied underdifferent ambient oxygen concentrations for up to 14 days in culture. The results indicated that the rate of lipofuscin accumulation was enhanced by the lytic enzyme inhibitors as well as by increase in the ambient oxygen concentration. The finding shown that the specific lysosomal proteinase inhibitor, E-64, is a considerably more effective enhanced of lipofuscinogenesis than leupeptin, which also inhibits proteinases other than intralysosomal. Effects of Al, Cd, Cr, Cu, Hg, Pb and Zn chloride on lipofuscinogenesiswere examined on rat myocytes after 14 days in culture under 5, 20 and 40% oxygen concentrations. Addition of Al, Cd, Hg and Pb to the culture medium markedly increased the level of lipofuscin accumulation, whereas Cr, Cu and Zn had the opposite effect (paper V). Both effects were more pronounced at higher oxygen concentrations. Lipofuscin may, or may not, have influence on cellular metabolism, directly or via its influence on the function of the lysosomal vacuome. This question is so far completely unresolved, probably due to inadequate experimental conditions. Our cell culture model seems to be a suitable system also for further functional studies
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| 16. |
- Otamiri, Grace
(författare)
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Neurological adaptation of full-term newborn infants : Influence of intrauterine growth accleration, intrapartal asphyxia and different modes of delivery
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Grace Otamiri. 1991. Neurological adaptation of full-term newborn infants. Influence of intrauterine growth acceleration, intrapartal asphyxia and different modes of delivery. The neurological adaptation was studied in full-term newborn infants of different categories. Mother-infant relationship, neurology and development at 6 months of age were also evaluated. Large-for-gestational age (LGA) infants showed fewer optimal neurological responses on the first day of life, as compared to appropriate-for-gestational age infants, used as controls. There were no neurological differences between prenatally and postnatally detected LOA infants. Infants with intrapartal asphyxia, born after emergency cesarean section (CS) were significantly more hypotone the first 2 days after delivery than infants born after elective CS. When compared with control infants, infants born after elective CS were more hypotone and showed less excitability (alertness) during the first 2 postnatal days and had reduced number of optimal responses during the first 5 days. No neurological differences were found between the CS infants delivered with general or epidural anaesthesia. The follow-up studies at 6 months of age showed no differences in either growth, neurology or development of the infants born after CS, vaginal breech and the controls. The catecholamine levels in cord blood were lower in elective CS infants as compared to vaginally delivered infants. A significant correlation was found between low levels of noradrenaline and poor muscle tonus and low grade of excitability on day 1. Mothers in the elective CS group had significantly more doubts about their capacity to care for their babies at the maternity ward as compared to the controls. However, at 1 month after delivery the elective CS mothers significantly contributed more caretaking for their babies. In conclusion, factors as the fetal size, intrapartal asphyxia and mode of delivery influence the neurological adaptation of full-term infants during the first days of life. The neurological dysfunction was transient and did not affect the health of the infants who all showed normal growth, neurology and psychomotor development at the 6-month follow-up.
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| 17. |
- Persson Borres, Magnus
(författare)
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Metachromatic cells and eosinophils in atopic children : A prospective study
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Metachromatic cells and eosinophil leukocytes were studied prospectively in 64 newborns with and without a family history of atopic disease (FH). Cellfindings in nasal mucosa and peripheral blood were related to development of atopic symptoms up to 18 months of age. For this purpose, a gentle scraping method suitable for infants was developed. Nasal metachromatic cells were more prevalent in atopic than in non-atopic infants. The cells were found in infants with respiratory allergy as well as in infants with eczema. Non-atopic infants with metachromatic cells all had FH. The cells were detected prior to or at the time of diagnosis. Thus, metachromatic cells are associated with atopic propensity as defined by development of atopic disease and/or a FH. Infants with respiratory allergy had more often acute otitis media compared to infants with eczema and non-atopic infants. Appearance of nasal metachromatic cells were associated with increased middle ear morbidity in atopic and non-atopic infants and high scores of cells correlated with high numbers of otitis media. Infants with respiratoryallergy may have otitis media as a result of the allergic condition. Blood eosinophils were studied in a total of 154 infants and were found to decrease with age. Blood eosinophilia at 3 months preceded atopic development but was not associated with FH. Nasal eosinophilia was a common finding in atopic and non-atopic infants. In conclusion, appearance of nasal metachromatic cells and blood eosinophilia are associated with atopic disease and may have roles as predictors of atopic disease.
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| 18. |
- Tysk, Curt
(författare)
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Epidemiology and genetics in ulcerative colitis with special reference to twins and smoking
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In an epidemiologic study of ulcerative proctocolitis during the period 1963-1987, annual incidence rates increased fourfold and was during the last 10 years 13.1/105 inhabitants. The prevalence on December 31, 1987 was 234/105 inhabitants. Both rates are high but close to recent reports. No second peak in older age groups and no cohot t at higher risk for the disease was found. The male:female ratio was 1,59:1, and the highest incidence rate was seen in 20-40 year old men, who to a higher extent than women were ex-smokers. The distribution of affected male and female cases has changed during the last 60 years. A review of 56studies from 1930-1990 revealed that the earlier female predominance now has been replaced by a male predominance. The age at diagnosis increased 7 years by the end of the study period. With respect to the sex-distribution and the age at diagnosis, a hypothesis is proposed that an environmental factor, viz smoking, has caused this changing pattern. The genetic influence was analysed in a study of 36 twin pairs with ulcerative colitis, of which 16 pairs were monozygotic. The proband concordance rate among monozygotic twins was 6.3%, and the heritability of liability 0.53. No concordant pair was found among the dizygotic twins. A comparison indicated that the genetic influence was less significant inulcerative colitis than in Crohn's disease. Earlier reported twin pairs with ulcerative colitis probably overestimated concordance rates due to selection bias. Abnormal colonic glycoproteins have earlier been reported in ulcerative colitis. Colonic glycoproteins were analysed in the monozygotic twins according to the method described by Podolsky et al. Similar alterations in glycoprotein composition were found in both the twins with ulcerative colitis and in their healthy twin siblings, indicating that changes in colonicglycoproteins probably are genetically defined, precede the onset of colitis and are not a secondary consequence of inflammation. A case-control study of smoking habits at the time of diagnosis was performed among 260 cases and 455 matched population controls to evaluate the association between smoking and ulcerative colitis. Compared to lifetime non-smokers, a reduced risk of acquiring ulcerative colitis was seen among smokers (relative risk 0.6) which seemed to be dose dependant. Exsmokers had an increased risk, which was especially increased in former heavy smokers (relative risk 4.4). A study of primary sclerosing cholangitis in ulcerative colitis showed a prevalence of 3.7%. Male excess and extensive to total colitis was found in the cases complicated with cholangitis, which in most cases was asymptomatic and had a non-progressive course. As 15 of the 16 monozygotic twin pairs were discordant for ulcerative colitis, the combination of identical genotype, shared environment in childhood and adolescence, similar levels of colonic glycoproteins and similar smoking habits is apparently not sufficient to cause manifest colitis and additional factors are needed.
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| 19. |
- Wingren, Gun, 1954-
(författare)
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Epidemiologic studies of health hazards related to the Swedish art glass industry
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The production of glass began a few thousand years B. C. but was not introduced in Sweden until the 16th century. In general, throughout history, technical development has been rapid, but considering the art of glass blowing, methods used today are much the same as when the blowpipe was invented about 2 000 years ago. The composition of glass has changed, however, as a result of production specialization and the introduction of different types of glass (e.g. lead crystal, opal and heat-resistant glass).Workers in the Swedish art glass industry are exposed to a variety of hazardous chemicals, some of which are known carcinogens. Most of these substances are components of the glass batch (i.e. the mixture of substances used to make glass), for example, compounds of arsenic, antimony, lead, cadmium, chromium, and nickel. Furthermore, large amounts of hydrofluoric acid and sulphuric acid are used in the polishing process, and, in the past, equipment made of asbestos was used for handling hot glass. Many of these chemicals are found not only within the glassworks themselves, but have also been emitted to the environment, causing general concerns about health hazards among people living inthe vicinity of glassworks. Some glass workers are also exposed to combustion products and constant heat stress when working close to the glass furnaces.The present studies show that Swedish art glass workers run increased risks of dying from cancer of the stomach, colon and lung and from cardiovascular diseases. In one of the studies, increased risks were also observed for prostate and pharynx cancer and for cerebrovascular diseases. The worker category showing the highest cancer risks was the glass blowers. The exposure route for this category of workers might be through both inhalation of airborne substances and ingestion of particles entering the mouth by way of the blowpipe. These possibilities are supported by hygienic measurements, including analysis of slag samples from inside the blowpipes.The present studies were initiated due to concern about cancer risks expressed by people living close to glassworks, but the only increased risk found in this population was a cluster of brain cancers. Glass workers represent a large part of the population living in the vicinity of the glassworks, where the cluster of brain cancers occurred, and because of this, registry-based studies of Swedish glass workers seem to have spuriously indicated an occupational risk in this respect. Although the detected cluster of brain cancers might have its origin in some industrial discharge from the glassworks, the chemicals predominating in the emissions are not known to cause brain cancers, and other factors might be involved as well.The cancer risks observed among glass workers can probably be explained by the known effects of several of the exposures occurring in glass production. The observed adverse effects on the cardiaand cerebrovascular systems may also be related to exposures at hand, first and foremost probably to lead exposure.
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| 20. |
- Wørlich Pedersen, Stephen
(författare)
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Neurophysiological evaluation of the motor performance in patients with Parkinson's disease
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study, comprising six separate papers, is concerned with the description and evaluation of some of the motor disturbances seen in Parkinson patients. Motor performances with different complexity in movement were investigated in patients with ideopathic Parkinson's disease. Muscle contraction characteristics were studied by electrical stimulation of the ulnar nerve and recording of the tension in the adductor pollicis muscle. Voluntary muscle contraction over a "single" joint was tested by concentric and eccentric isokinetic strength measurement including a stretch-shortening cycle. A semiautomatic voluntary movement with important postural components was tested by assessment of basal gait characteristics. Clinical scoring was performed according to Webster and the Hoehn and Y ahr rating scale. The relevance of the tests for evaluation of Parkinson's disease was tested by, a) withdrawal of medication, b) physiotherapeutic training, c) comparison with control subjects of the same age as the patients.The results showed that the contraction and relaxation characteristics of muscle contraction were shorter than in normals, but was not influenced by withdrawal of medication. Isokinetic muscle strength in ankle dorsiflexors in patients were lower in all contractions types andangular velocities, when compared to controls. Strength impainnent was greater in men than women. Strength was influenced by withdrawal of medication. Muscle contraction was performed with a lower efficiency than in nonnals. Muscle stiffness did not seem to impair strength. Gait in patients was disturbed with a shorter stride length and a lower gait velocity than in normals.Gait parameters were further disturbed, when medication was withdrawn. Nonnalization to constant velocity and constant stride duration improved the analyzis. Men were found to be more disabled than women. Gait, but not strength, correlated to the clinical score in group comparisons, but in intraindividual comparisons a correlation between strength and clinical score was found. Gait and strength parameters were not influenced by physical group training. The conclusion of the study was that motor analysis, employing different levels of complexity in motion, can be useful in the description of motor impairment and therapy in Parkinson's disease.
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