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  • Broqvist, Mats, 1955- (författare)
  • Clinical studies in severe heart failure : neurohormonal, electrolyte and metabolic aspects
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Congestive heart failure is a common and complex syndrome with a poor prognosis. Although heart disease is usually the primary event, the clinical syndrome is characterised by several extra-cardiac manifestations. Neurohormonal activation seems to play a crucial role for these manifestations and the progression of the disease.Twenty-seven consecutive patients with acute left ventricular heart failure were found to have increased plasma concentrations of atrial natriuretic peptide, arginine vasopressin and catecholamines, while the renin-angiotensin system was not activated until diuretic therapy was introduced. To counteract this activation it seems suitable to combine the diuretics with an angiotensin-converting enzyme inhibitor.Skeletal muscle biopsies were performed in 22 patients participating in the CONSENSUS trial, which was a randomised, double-blind, placebo-controlled study of the effects of the angiotensin-converting enzyme inhibitor enalapril on mortality in patients with severe congestive heart failure. The biopsies revealed decreased content of magnesium andpotassium while sodium and water were retained in skeletal muscle. Ventricular arrhythmias occurred frequently. The ventricular arrhythmias seemed to be related to lower serum levels of potassium, but no significant correlations were found to muscle electrolyte content. This may indicate that the ratio of electrolytes across the cell membrane is moreimportant for the development of arrhythmias than changes in the absolute amount of electrolytes are. The muscle biopsies also revealed metabolic derangement with decreased content of energy-rich compunds, such as adenosine triphosphate (ATP), phosphocreatine and glycogen,Treatment with enalapril did not seem to influence these peripheral abnormalities, but some beneficial effect was found regarding the prevalence of ventricular arrhythmias.In another 22 patients with severe congestive heart failure, similar signs of energy depletion were found in skeletal muscle biopsies. Nutritional assessment, based on anthropometry and serum protein levels, revealed signs of malnutrition in only two patients which is in contrast to a previous reported prevalence of 30-50 % in patients with severe congestive heartfailure. Long-term oral dietary supplementation, given in a randomised, double-blind and placebo-controlled manner, did not change muscle energy content, neither did exercise tolerance improve. Thus, malnutrition did not seem to be a prerequisite for the metabolic changes found in skeletal muscle. Consequently, routine dietary supplementation does not seem to be indicated in patients with congestive heart failure.
  • Carlsson, Margaretha S. (författare)
  • Pharmacokinetics of 2-mercaptopropionylglycine (Tiopronin) in man
  • 1993
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • 2-Mercaptopropionylglycine (2-MPG, tiopronin) has been used successfully in the treatment of cystinuria despite the lack of knowledge of its pharmacokinetics. Therefore methods based on high-performance liquid chromatography and fluorometric detection were developed for quantitative analysis. The total, non-protein-bound, and free (thiolic) tiopronin were measured in plasma using this method.The phannacokinetic disposition of tiopronin in plasma after intravenous administration was best described by a three exponential function. Plasma concentration time-curves of total tiopronin exhibited a rapid distribution phase, a B-phase corresponding to renal excretion, and a long terminal elimination phase. The latter was the result of strong disulphide binding of tiopronin to proteins. The non-protein-bound tiopronin was eliminated faster judging by its early appearance in urine. Mean bioavailability was 63 % in healthy volunteers with great interindividual variability (range 33-91%).Multiple dosing studies gave similar pharrnacokinetic parameters as for single dose studies and studies on patients with renal impaitment elucidated the renal clearance of the drug. In vitro studies showed a slow dissolution of the drug dosage form employed. A metabolite, 2-mercaptopropionic acid, was identified and its pharmacokinetics was investigated. The mechanism of action of the drug is discussed based on the results of measuring free tiopronin in plasma.
  • Cederholm, Ingemar, 1951- (författare)
  • Ropivacaine : An experimental and clinical study with special reference to analgesic, circulatory and antiinflammatory effects
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Aims of the study: 1. to compare ropivacaine, a new long-acting amino-amide local anaesthetic drug, and bupivacaine (with/without adrenaline) concerning dermal analgesia and local vascular effects, 2. to design a suitable test procedure to evaluate changes in skin blood flow after intradermal injection of local anaesthetics, 3. to evaluate changes in skin blood flow of various concentrations of ropivacaine with/without adrenaline, 4. to investigate the influence of ropivacaine, bupivacaine, lidocaine, mepivacaine and prilocaine on the production of oxygen metabolites in human polymorphonuclear leukocytes (PMNL) (intra- and extracellular reactions), and 5. to examine the neural blocking characteristics on sensory, motor and sympathetic pathways using ropivacaine for epidural analgesia.72 male patients scheduled for transurethral surgery and 50 male volunteers participated in this work. Heparinized blood was obtained from a total of 29 healthy adult blood donors.Dermal analgesia was evaluated by pin-prick, skin colour changes by visual inspection, skin blood flow by laser Doppler flowmetry, sensory blockade by pin-prick, motor blockade by a modified Bromage scale, sympathetic blockade by assessments of skin resistance level (SRL) and response (SRR), skin temperature and skin blood flow (laser Doppler flowmetry). Production of oxygen metabolites by PMNLs was measured by luminal-enhanced chemiluminescence (intra- and extracellular reactions).Ropivacaine produced significantly longer duration of dermal analgesia, following intradermal injection (0.1 ml, 30-G needle), compared with bupivacaine, in comparable concentrations. Addition of adrenaline increased the duration of both local anaesthetics. Local blanching was more frequent for plain solutions of ropivacaine.The effect of drugs on local circulation may well be studied by intradennal injection (0.1 ml, 30-G needle, volar surface, forearms) and recording of changes in skin blood flow (laser Doppler flowmetry). The intradennal injection of a local anaesthetic drug may produce not only a further increase but also a decrease in skin blood flow, if the effect of an intradermal saline injection, causing a very reproducible flow increase, is considered in the evaluation of the net circulatory effect of the tested drug.Intradermal injection of lidocaine 1% and bupivacaine 0.75% produced an increase in skin blood flow. Ropivacaine 1% produced a flow similar to saline, while a decrease was seen for ropivacaine 0.75%. Ropivacaine0.5%, 0.375%, 0.25%, 0.125% and 0.063% showed a gradual further reduction in flow, where 0.063% produced a flow similar to adrenaline-injection (5 Jlg/ml) and almost as low as at the untreated control sites. The combination of ropivacaine 1%, 0.5% , 0.25% and adrenaline did not accentuate but instead decreased the vasoconstrictive effect of adrenaline.By and large a decrease in response of chemiluminescence for PMNLs was seen with the higher concentrations of the various local anaesthetics. Lidocaine showed a minor decrease even at lower concentrations. Ropivacaine 1000 J.Lg/ml showed a depression of both intra- and extracellular responses that was similar to, and even somewhat more pronounced than lidocaine 1000 J.Lg/ml. This effect could be of great interest e.g. for local antiinflammatory effects by topical administration, but it has to be further investigated. A marked increase for prilocaine (1000 Jlg/ml) in intracellular response accompanied with a reduction in extracellular response was noted.Ropivacaine (0.5%, 0.75% with/without adrenaline) 20 ml administered epidurally provided a good sensory blockade and a motor blockade satisfactory for transurethral surgery. The maximum sensory level of analgesia was high, median Th 2-3. The majority of patients had a marked or complete sympathetic blockade in the lower limbs. Besides mild or moderate hypotension, which responded well to treatment with ephedrine, no other serious adverse reactions were seen, Addition of adrenaline did not provide any significant prolongation of the epidural blockade, and did not alter the influence upon the sympathetic blockade nor the hemodynamic changes during onset.
  • Comba, Pietro (författare)
  • Epidemiologic studies of nasal cancer and occupational exposures
  • 1992
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The object of the present research has been to elucidate the associations between malignant epithelial neoplasms of the nasal cavities and paranasal sinuses and workplace exposures to ascertained as well as suspected cancer causing agents and processes.The research includes six independent case-control studies, located in various Italian regions. These regions are characterized by different patterns of industrialization, resulting in an involvement of various occupations of interest. Furthermore, the main findings of a national programme of surveillance of nasal cancer are presented.The regions selected for the studies were the district ofBiella in Piedmont (high proportion of the active population employed in textile industry), the province of Brescia in Lombardy (high proportion of the activepopulation employed in metal industry), the provinces of Verona and Vicenza in Venetia (an area characterized by textile and leather industry and by farming), the province of Siena (a mainly rural area, with a well-established wood industry) and the province of Pisa (characterized by the presence of wood and leather industry); the two latter provinces are both located in Tuscany. The national surveillance program was based on the collaborative effort of 61 ear, nose and throat departments operating all over Italy. Finally, a case-control study involving subjects from the National Cancer Institute in Milan provided information at a national level, since patients from all over the country attend this centre.The present research confrrmed the well established risk of nasal cancer associated with the occupations of woodworker and leatherworker. The combined estimates of the odds ratios were 6.0 (90% CI: 3.8-9.3) and 5. 7 (90 % Cl: 2.8-12), respectively, which are lower and somewhat less dramatic effects than seen in some of the earlier studies.A significant association between nasal cancer and some other occupations was detected, namely metal industry, the combined estimate of the odds ratio being 2.3 (90 % Cl: 1.2-4.3), textile and gannent industry (OR: 2.2; 90% Cl: 1.2-4.1), mining and construction industry (OR: 2.8; 90% Cl: 1.6·5.0), fanning (OR: 2.3; 90% Cl: 1.4-3.8) and other occupations entailing exposures to dusts and fumes (OR: 2.0; 90% Cl: 1.1-3.6).The etiologic fraction associated with all hazardous occupational exposures was about 60 %, indicating that a considerable preventive effect could be achievable by improving the quality of the work environment. With regard to the high fatality of this disease, and the serious impairments of quality of life among the survivors, the importance of prevention is not only obvious but also ethically imperative.
  • Croner, Stefan, 1944- (författare)
  • Development of atopic disease from birth to adolescence : Relation to family history and cord blood IgE
  • 1991
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • In a cohort of 1701 consecutively born children, 32.5% developed obvious atopic disease up to 11 yr. The predictive capacity of cord blood IgE and a family history (FH) of atopic disease have been studied. Questionnaire (Q) data at 1.5, 7 and 11 yr showed a prevalence of obvious atopic disease of 4.5, 11.5 and 23.7 % respectively. The prevalence of asthma was 0.5, 2.4 and 3.0 %, a slight increase in comparison with figures from the 50's. A high cord blood IgE (~ 0.9 kUJI), identified most children with early, multiple and continuous symptoms as well as an earlier asthma start. The capacity of cord blood IgE to predict the severity of asthma and the IgE levels at 11 yr was low. The sensitivity of the test to detect atopic disease decreased from 77 % at 1.5 yr to 26 % at 11 yr. The sensitivity for obvious allergy of a FH was 49 % at 1.5 yr and 45 % at 11 yr. The specificity of cord blood IgE was 94 % at 11 yr and of the FH 74 %. Cord blood IgE determination alone can not, without modifications, be recommended as a general screening method for atopy. Children with high cord blood IgE, born during peak pollen exposure seem to be at special risk to develop atopic disease. Sensitization to timothy was more common among children born in May as compared to November. The reliability of the Q used at 7 and 11 yr was evaluated by examination of 133 randomly selected children at 11 yr. The Q was found adequate for establishing the prevalence but less so for the cumulative incidence of atopic disease since parents tend to forget symptoms (25%) that their children had some years earlier. The natural history of asthma (AB) was studied in all 89 children and adolescents reporting symptoms of asthma. Fifty-nine were available for clinical examination at 11.5-14.5 yr. AB was found more often in children born during August-October. Inadequate medication, undiagnosed chest deformity and wheezing at examination was found in several children emphasizing the need for more regular control of adolescents having AB. Animal danders and pollens were the most common offending allergens. Sensitivity to mites was more common compared to earlier Swedish studies. A "total asthma score" including both days with impact of AB during last year and present medication was found useful for classification of these children with AB.
  • Ekberg, Kerstin, 1948- (författare)
  • An epidemiologic approach to disorders in the neck and shoulders
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Complaints about pain in the locomotor system represent a commonly occuning health problem among working people all over the world. In this context, a series of studies were employed to determine if work organization and psychosocial conditions at work, in addition to physical work load, contribute to the development of disorders in the neck and shoulders. The potentially health-promoting effect of early and active rehabilitation of those already suffering from disorders in the neck and shoulders was also evaluated.A first psychophysiological study showed that various stress conditions during monotonous work had limited effects on muscle tension. The interindividual variability in muscle reactions to stress was large, but the results indicate that some individuals may react with a sustained, low-level muscle activity that is associated with pain.A cross-sectional study of a sample of a normal working population and a case-control study of patients with disorders in the neck and shoulders revealed a set of work-related core determinants, which appear to be essential component causes for the development of symptoms and signs. Prevalence ratios (PR) were calculated for determinants of early symptoms in the cross-sectional study, and odds ratios (OR) were estimated in the case-control study for determinants of disorders of the neck and shoulders. Repetitive movements demanding precision (PR 1.2 and OR 7.5, respectively), high work pace (PR 1.2 and OR 3.5, respectively), low quality work content (low decision latitude and lqw skill discretion; PR 1.3 and OR 2.6, respectively), and uncertainty about how to perform and-manage the tasks (work-role ambiguity; PR 1.2 and OR 16.5, respectively) were associated with both development of early symptoms, and disorders in the neck and shoulders. The results also show that being a woman (PR 1.3 and OR 11.4, respectively) and I or an immigrant (PR 1.3 and OR 4.9, respectively) imposes a higher risk for developing signs and symptoms in the neck and shoulders, possibly due to selective job-assignment.A controlled, two-year follow-up of cohorts of subjects with early and active rehabilitation versus traditional, less active treatment of neck~shoulder disorders respectively, did not support the hypothesis that active rehabilitation, as compared to traditional treatment methods, promotedbetter health, unless work conditions were changed. People who remained on the same job after rehabilitation, independent of type of treatment, had a less positive prognosis (relative risk 3.6) than those who had a changed work situation.Further analysis of which factors retained people in long-term sick-leave suggested that work conditions are more important than personality and other individual characteristics in determining the amount of time that will elapse before individuals will resume work after a sickleave. There was no gender-difference in this respect.
  • Engdahl, Olle (författare)
  • Treatment of pneumothorax : Aspects on diagnosis, treatment technique and pain relief during drainage treatment
  • 1993
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Pneumothorax is the term used for all conditions where air is present in the pleural cavity outside the confinement of the lung. Active treatment of pneumothorax often consists of the introduction of a pleural drain and the application of a continuous vacuum to keep the collapsing lung expanded until the lesion has healed. Traditional techniques for the application of vacuum do not permit quantification of aspirated air volumes during treatment and assessment of the correct time to stop treatment rests on a purely subjective basis. The patients require hospitalisation during treatment which is often painful. The decision to institute active treatment usually relies on estimation of the volume of the collapsed lung pertormed from a chest X-ray.The aims of this study were to investigate if treatment using equipment permitting quantification of aspirated air volumes could reduce treatment time, if the treatment could be made less painful and if chest X-ray was a reliable method for estimating the size of the pneumothorax.A new device for vacuum treatment of pneumothorax was developed and six studies in 289 cases of pneumothorax were undertaken.The studies showed that when the new technique was applied in 124 cases of traumatic and spontaneous pneumothorax, treatment time was reduced significantly compared to when the traditional technique was used. In a placebo-controlled, randomised study in 22 patients suffering from spontaneous pneumothorax it was demonstrated that pain relief during treatment was improved by the use of an interpleural technique for analgesia employing the injection of a local anaesthetic agent into the pleural cavity. This technique using 20ml bupivacaine-epinephrine 0.5% injected at 8-hourly intervals for three days did not produce serum concentrations in the toxic range, but small haemodynamic changes were registered possibly caused by beta-adrenergic stimulation by the epinephrine. A study on 16 patients with spontaneous pneumothorax showed that estimation of the degree of lung collapse from chest X-ray was unreliable as this correlated poorly to an estimation made on the same patient using CT-scan.
  • Engvall, Jan, 1953- (författare)
  • Aortic coarctation : Physiological and model studies
  • 1993
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • In 22 patients, referred for the assessment of significant native- or re-coarctation, the systolic cuff blood pressure difference between arm and ankle at rest and after three different subrnaximal exercise tests and one maximal test was compared with invasive blood pressure. Reference values of cuff blood pressure were obtained from 19 healthy adult volunteers. The cuff blood pressure difference at rest correlated closely with the invasive pressure difference and the degree of constriction as assessed by angiography. The cuff blood pressure difference one minute after the different exercise tests varied with the load. A pressure difference of 50 mm Hg one minute after submaximal treadmill exercise identified all individuals with an invasive pressure difference exceeding 50 mm Hg during supine exercise. After maximal exercise, a large difference was seen between arm and ankle in healthy subjects as well as in patients.Theoretical analysis and pressure measurements across a constriction in a physical flow model showed a relation between mean pressure and flow that could be expressed as a power function. Pressure recovery was 0-4 mm Hg in the model and of similar magnitude in patients.Simulations in a computer model of the central circulation showed that the downstream pressure and flow depended strongly on the properties of the collaterals. The length and diameter of the collateral influenced the transmission of pressure and flow, while collateral wall stiffness did not. The resistance and wall stiffness in the upstream circulation exerted an important influence upon the upstream pressure.Twenty patients, of whom 16 had undergone coarctation surgery, were investigated with bi-plane transoesophageal echocardiography (TEE) as well as with continuous wave Doppler from the suprasternal notch and magnetic resonance imaging (MRI). Seventeen healthy volunteers were investigated with MRI to obtain reference values. MRI in the axial plane showed the largest coarctation diameter, mean difference between methods 1.4±3.5 mm. Coarctation systolic velocity was 0.23 m/s higher with Doppler than with MRI. MRI peak flow ratio between the descending and ascending aorta showed a linear correlation with Doppler velocity and is proposed as a new measure of obstruction to flow.Twenty-four-hour non-invasive ambulatory blood pressure monitoring, performed on the 20 patients mentioned above, showed a significant negative correlation between the systolic blood pressure level and coarctation diameter, suggesting a remaining influence of the coarctation on the blood pressure even in patients who had undergone surgery.
  • Esbjörner, Elisabeth, 1947- (författare)
  • Studies on albumin binding properties in pregnancy and early infancy : with special reference to maternal sulphasalazine treatment
  • 1990
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Sulphasalazine (SASP) has been avoided during the later part of pregnancy and during breast-feeding as some sulphonamides possess the ability to displace bilirubin from albumin and thus increase the risk of bilirubin-induced brain damage in jaundiced neonates. However, withdrawal of SASP in a woman with ulcerative colitis would mean a cqnsiderable risk of relapse of her disease.In this study, SASP and its metabolite sulphapyridine (SP) was shown to pass the placenta. Sulphapyridine but not SASP appeared in breast-milk, although concentrations in breast-fed infants were low. The substances were eliminated slower in newborns than in adults.The possible bilirubin-displacing effect of SASP and SP was evaluated by using the MADDS (monoacetyldiaminodiphenyl sulphone) method to determine the binding 'properties of serum albumin.MADDS is used as a deputy ligand for bilirubin. In vivo and in vitro studies, using the MADDS and the peroxidase methods, showed that SASP and SP in pharmacological concentrations did not displace bilirubin from albumin.During that study it was noted that the reserve albumin concentration for MADDS was far lower in women at delivery than in non-pregnant women. In a longitudinally followed group of pregnant women, the reserve albumin concentration was gradually lowered during pregnancy, reaching 530/o of the concentration in non-pregnant women at term. This can have pharmacokinetic effects on those drugs that share the binding function on albumin with MADDS and bilirubin. The reduction of the reserve albumin concentration was due to a reduced albumin concentration during pregnancy but also to a reduced binding ability of the albumin molecule.
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