| 1. |
- Afoke, Anthony Okoro
(författare)
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Some epidemiological aspects of insulin-dependent diabetes mellitus in Nigeria and Sweden
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the western world diabetes mellitus is one of the most common severe diseases in childhood, but it is rarely seen in black African populations. However, there are very few epidemiological studies of childhood diabetes in Africa and almost nothing is known of the Nigerian population. One aim of this study was therefore to estimate the prevalence of insulin dependent diabetes (IDDM) in children and adolescents and to characterize their type of diabetes.A screening of almost 78,000 school children was performed and beside some already known diabetic patients several new cases were diagnosed. It was found that IDDM is much less common than in Europe but on the other hand more common than in several Asian countries. In addition the prevalence found may be underestimated because of cultural and social factors, health care problems and high mortality in diabetes. Although most patients had a clinical picture of Malnutrition Related Diabetes (MRD) we found in some cases autoantibodies towards islet cells and insulin and furthermore the same HLA-DQ-type-associations as seen to Type 1 diabetes in caucasian diabetics.While we saw no seasonal variation of diagnosis of Nigerian IDDM, there is a pronounced such seasonal variation in Sweden. This study has tried to elucidate whether this seasonal variation is related to any differences in manifestation and clinical course. Patients diagnosed during incidence peaks had more often short duration of symptoms before diagnosis,ketonuria at diagnosis, rapid loss of endogenous insulin secretion but increase of insulin antibodies and of glycosylated haemoglobin. They had also more often infections before diagnosis and high serum immunoglobulins (IgG and IgM) up to 9 months after diagnosis. HLA-DR4 was more common in these patients. The results suggest that IDDM in Swedish children is heterogenous.
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| 2. |
- Blomberg, Björn, 1948-
(författare)
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Helicobacter pylori : Prevalence, heterogeneity, and ulcerogenic properties
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In 117. unselected patients H. pylori infection was found in 49.6% by combining culture and acndme orange stammg of hssue sections. Infection was equally common in the gastric body and antrum. The activity of gastritis was generally higher in the antrum. The overallagreement between acridine orange stain and culture was 0.93.Formalin treated H. pylori whole cells were used to immunize rabbits. With the aid of coagglutination and indirect immunofluorescence all H. pylori strains tested were shown to contain cross reactive antigens, but no serum cross-reacted with all strains tested. Multiple, antigenically different, isolates were found in some patients and a provisional serogrouping based on heat-stable antigens was proposed.Acid glycine extracts from four H. pylori strains were prepared. Rabbit antisera against these, and ten further, strains showed extensive cross-reactions with all four extracts. An EIA based on H. pylori strain NCTC 11637 had a sensitivity of 90 % and a specificity of 87 %.In 197 unselected patient culture, histopathology using acridine orange or Giemsa staining, and serology was evaluated. 33.5 % of patients were infected by H. pylori. The sensitivities for culture/acridine orange stain/Giemsa stain were 0.94/0.86/0.91 respectively. The specificities were 1.0/1.0/0.84. For two commercial serologic tests the negative predictive values were 0.93/0.95 respectively. A strategy of serologic screening to avoidunnecessary endoscopies was suggested, but that positive serology be confirmed by histopathology.Sixty-one human gastric isolates of H. pylori were tested for their ability to induce oxidative burst in human neutrophils. A cell bound, heat-labile, property able to induce a strong and rapid oxidative burst in neutrophils in the abscence of opsonins, was found in about one third of strains tested. This property was significantly associated with peptic ulcer disease(p=0.0261, Fisher's exact test).Fifty-four clinical isolates of H. pylori were tested for cytotoxin production and their ability to induce oxidative burst in human neutrophils. Nonopsonised, 20 strains showed a rapid and strong oxidative burst, 30 a slow and weak response, and four remaining gave inconclusive results. Cytotoxin production was seen in 10 of 20 rapid and strong inducers, but only in 3 of 30 with a slow and weak response (p=0.0027, Fisher's exact test). 11/15 of the cytotoxin producing strains (p=0.0135) and 13/20 of the rapid and strong inducers (p=0.0209) were from 22 patients with peptic ulcer disease. The ability of some nonopsonised H. pylori to activate neutrophils showed eo-variation with cytotoxin production, but the two properties seem to be independent markers of peptic ulcer disease.With theuse of electron microscopy the interactions of human neutrophils with four nonopsonised H. pylori strains, two rapid and strong, two slow and weak inducers of neutrophil oxidative burst were studied in morphologic detail. The rapid inducers were phagocytosed within minutes, whereas the slow inducers showed little reaction even after one hour.Conclusions: Histopathology using acridine orange or Giernsa stains correlates well with culture. Serologic screening might be of value to reduce unnecessary endoscopies. A cellbound heat-labile property of some H. pylori strains able to nonopsonised induce a rapid oxidative burst in neutrophils is significantly associated with peptic ulcer disease. This property is also associated with, but independent of, cytotoxin production.
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| 3. |
- Carlsson, Margaretha S.
(författare)
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Pharmacokinetics of 2-mercaptopropionylglycine (Tiopronin) in man
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
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| 4. |
- Engdahl, Olle
(författare)
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Treatment of pneumothorax : Aspects on diagnosis, treatment technique and pain relief during drainage treatment
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
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| 5. |
- Engvall, Jan, 1953-
(författare)
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Aortic coarctation : Physiological and model studies
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
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| 6. |
- Gadegaard Jensen, Anders
(författare)
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Clinical and laboratory studies on propofol
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients undergoing major abdominal surgery were randomly given total intravenous anaesthesia based on propofol and fentanyl, anaesthesia based on propofol, fentanyl and nitrous oxide or anaesthesia based on isoflurane and fentanyl. Postoperative atelectasis demonstrated by computed tomography of the chest was found to a similar extent and a similar decrease in arterial oxygen pressure was seen in the groups. No correlation was seen between the size of atelectasis and postoperative oxygen pressure. Cardiovascular stability was equally well maintained during surgery, but the patients anaesthetized with propofol needed more ephedrine and glycopyrrolate to achieve stability. In all groups the Acute Physiology Score was normal by day I (range 1-7). A similar impairment of bowel function after operation was found, with passage of gas day 3 ( 1-6) and tolerance of enteral intake day 5 (1-10). Hospital stay 11 (6-45) days and incidence of complications were unaffected by anaesthetic technique. Early recovery was similar in the three groups, but patients anaesthetized with propofol reported fewer symptoms, better subjective control and a higher degree of socially orientation than patients anaesthetized with isoflurane. On the whole, the advantages with propofol compared to isoflurane were small, and the addition of nitrous oxide to propofol had no influence on. the results.Laboratory tests on human leucocytes, cultured human glial cells and rat glial cells and neurons were performed with propofol in concentrations between 0.3 ~g·ml" and 50 ~g·ml" (1.7 to 280 ~M). Clinically relevant concentrations of propofol decreased random and chemotactic locomotion of leucocytes in an agarose assay. Concentration dependent and reversible effects of propofol were found on the actin distribution of the cytoskeleton in cultured cells. The maximal effect was seen after 20 min of incubation. Using a single cell microfluorometric method with Fura2 an increase in cytosolic free calcium in rat neurons was seen immediately after the addition of propofol, lasting 128±39 seconds and thereafter returning to normal. This effect was dual, 60-7 5% of the increase came from the extracellular buffer and the remaining part from intracellular stores. A rise in intracellular calcium can lead to changes in the cytoskeleton and to hyperpolarization of a neuron.
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| 7. |
- Good, Lars, 1953-
(författare)
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Anterior cruciate ligament reconstruction : Anatomic and biomechanical considerations of graft placement and fixation
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study, comprising 7 separate papers, is concerned with the mechanical causes of graft failure after intraarticular reconstruction of the anterior cruciate ligament (ACL). The study is predominantly experimental in design, but a clinical follow-up is also included to test a causal hypothesis of secondary graft elongation.Fixations of synthetic ACL substitutes with ligament staples had low security and the maximum tolerance loads were in parity with forces generated during daily activities, while screw fixations of looped ligaments had higher load to failure than a normal ACL.A stenosis, caused by osteophyte formation, was found at the intercondylar notch less than 2 years after an ACL tear, strongly suggesting impingement and wear as a possible mechanism of ACL substitute failure. The intercondylar notch was also found to be narrowed in patients with an acute tear of the ACL compared to a normal control group, thus implying causality.A standardized technique of graft placement, using a guide to aid bone drilling, was found more accurate and reproducible in achieving desired graft insertions compared to freehand drilling. This was evaluated by a new method for detennining the graft insertion locations on the femur and tibia, using a ratio related to the sagittal depth of the condyles.The ability to restore knee kinematics from an ACL deficient state, was evaluated for a drill guided graft route and an over-the-top route. The only effect of both methods, using a dacron graft tensioned in full extension, was restoring or partially restoring the increased anterior -posterior translation.A good in vitro and in vivo correlation was found between the patterns of change in dynamic fixation distance, as measured intraoperatively with an isometer, and tension in the fixed ACL substitute. The isometry measurement could not predict the magnitude of the frnal tension due to the biological variability in soft tissue compliance.Sagittal knee stability was measured at regular intervals for 2 years on patients who had an intraarticular ACL reconstruction with a patellar tendon substitute. Increasing anterior-posterior displacement was found for all patients as a group, and more for patients with an anterior femoralligament insertion location.A standardized treatment including aided bone drilling, notch plasty, isometry measurement, and restricted postoperative rehabilitation is recommended.
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| 8. |
- Gustafsson, Mikael
(författare)
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Motility of human polymorphonuclear leukocytes : An image processing approach
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cell motility is essential for polymorphonuclear leukocyte (PMN) function in the defense against invading microorganisms and in inflammatory processes. Using digital video microscopy and image processing, individual cells were studied during random locomotion, chemotactic locomotion and phagocytosis. When PMN moved in a specific direction, the lipid membrane was found to flow in the same direction, contradicting the rearward lipid flow model of cell locomotion. This was assessed with video photobleaching of a fluorescent lipid probe, Dii. The motility of PMN could not be blocked by ca2+ depletionand /or inhibition of myosin light chain kinase, suggesting that ea2+ and myosin are not necessary for locomotion. Temporal and spatial characteristics of intracellular free ea2+ and intracellular pH were assessed by loading the cells with esters of Fura-2 and the fluorcscein derivative BCECF, respectively. There was a distinct correlation between the direction of PMN locomotion and the slope of the Ca2+ gradient of the cells. PMN moving randomly on a surface often exhibited a rearward gradient with higher ca2+ concentration in the rear of the cell. Experimental reversal of the gradient, however, did not change the direction of motility. During phagocytosis of yeast particles, Saccharomyces cerevisiae, intracellular free calcium rose within seconds after contact with the prey. Intracellular pH varied between 7.1 and 7.3 and was uniform across the cells. After phagocytosis, phagosomal pH first decreased and then returned to neutraL A role for pH in phagosome-lysosome formation is proposed. PMN loaded with self-quenching concentrations of BCECF exhibited a strict correlation between pseudopod protrusions and increase in fluorescence, indicating water influx and dilution of the probe. This finding may be essential for the understanding of actin cytoskeleton dynamics during cell locomotion.
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| 9. |
- Janerot Sjöberg, Birgitta, 1958-
(författare)
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Aortic valvular flow : a clinical and experimental doppler echocardiographic study
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aortic blood velocity determination by ultrasound Doppler is a safe and valuable tool when evaluating patients with heart disease. The time-course of the velocity signal can be used for detemnining left ventricular function. In a mixed patient material, including patientswith ischaemic and valvular heart disease as well as heart transplants, stroke volume was noninvasively and accurately calculated during rest and exercise (-1 ± 7 m! [diffmean ±I SD]) using suprasternal pulsed Doppler registrations and parasternal 2D aortic anulus dimension imaging. Early during supine exercise (at 40% of upright maximal load) middleaged healthy women increased their cardiac output by 79%, stroke volume by 10%, aortic maximal flow velocity by 27% and maximal acceleration by 43%. This is in contrast to the reaction in women with coronary artery disease and previous infarction where no increase or, in certain patients, a fall in these variables was observed. In this way aortic ultrasound Doppler adds haemodynamic information to the conventional exercise test noninvasively.However, whether aortic ultrasound Doppler is used by itself (e.g. in calculations of velocity-changes, integrals and instantaneous pressure drop) or in combination with ultrasound tissue imaging (e.g. in calculations of cardiac output and stenotic valve areas), there are assumptions and simplifications made in the analysis. Theoretical and experimental analysis shows that a three-component Windkessel model is relevant when modelling early proximal aortic flow. Maximal aortic flow velocity and acceleration are not only influenced by the rate of pressure change - and thereby left ventricular con tractility - but also by aortic vessel characteristics. Besides the influence of aortic pressure change, maximal velocity is related to the compliance of aorta and great arteries and maximal acceleration inversely related to the characteristic impedance. This knowledge is of importance when interpreting the spectral Doppler signal. It also gives the future opportunity of assessing aortic compliance and characteristic impedance noninvasively if the aortic pressure change is known. For flow determinations by ultrasound Doppler, knowledge of the 3D flow profile is important. In calculations within the heart this profile is often assumed to be flat. Using 2D colour Doppler it is possible to .reconstruct a true spatial velocity profile using an external time delay device. A nearly flat, but slightly antero-septally skewed, flow profile was found in the subvalvular area in patients with moderate to severe aortic valvular stenosis and in these patients a parasternally measured flow diameter is a good estimate for the mean of two transverse flow axises. Stroke volume determination, using pulsed Doppler ultrasound in this area, may therefore be favourable in patients with aortic stenosis. In contrast to this, flow may be overestimated by more than 40% by using centerline velocity as an estimate of spatial mean velocity in certain patients with aortic regurgitation and in certain normals.
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| 10. |
- Kjellberg, Svante, 1946-
(författare)
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Zinc and human sperm chromatin
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- X-rny microanalysis, Sephadex® chromatography of seminal plasma and exposure of spermatozoa to sodium dodecyl sulphate (SDS), were methods used to study the zinc content of sperm chromatin, the nature of the zinc binding ligands present in seminal plasma and the stability of the sperm chromatin in whole semen samples from fertile and infertile men. Split ejaculates were used to study the same variables in different fractions of the same ejaculate.To obtain "pure" samples of prostatic fluid ejaculates were collected from four men with agenesis of the Wolffian ducts.Spermatozoa were obtained from the vas deferens and the ejaculates from each of four men operated on with vasectomy to study how contact between the sperm and seminal plasma might influence the eventual content of zinc in the sperm chromatin.The relative content of zinc in sperm chromatin was extremely low in the vasal spermatozoa as compared to the content of zinc in the chromatin of the ejaculated spermatozoa. This indicates that sperm may take up zinc from the seminal plasma. Another role for zinc in seminal fluid could be to prevent loss of zinc from the spenn chromatin of ejaculated spermatozoa.The proportion of sperm heads which remained stable after exposure to SDS was found to be related to the relative content of zinc in the sperm chromatin. The content of zinc in spermatozoa from fertile men corresponded to one zinc atom per protamine molecule in the chromatin.The relative content of zinc in the sperm chromatin had no simple relation to the zinc concentration in the seminal plasma. It was, however, found that men with a relative low content of zinc in the sperm chromatin had a disturbed sequence of ejaculation. They ejaculate the majority ofspennatozoa in an ejaculate fraction with a high admixture of seminal vesicular fluid. These fractions had a low zinc/fructose molar ratio i e a low ratio between prostatic derived zinc and vesicular derived fructose. Furthermore in these fractions seminal plasma zinc was to a high degree OOund to high molecular weight ligands (Zn~LnMw).The low molecular weight zinc binding ligand (Zn-LLMW) was shown to be of prostatic origin and identical to citrate.Sperm samples derived from fertile semen donors (n=5) a had a' higher proportion of sperm heads remaining stable after exposure to SDS, as well as a higher content of zinc in the sperm chromatin as compared to samples from group of men with "unexplained" infertility (n=lO). A larger sample of men investigated because of infertility (n=ll5) was also studied. Onequarter of these men had an impaired sperm chromatin stability with less than 80 per cent stable spermatozoa. The proportion zinc bound to the ligand Zn-LIIMW varied between 2~67 per cent. It is concluded that the liquefied seminal plasma, despite a high zinc concentration, could act as a zinc~ chelating medium that could deprive spermatozoa of zinc. It was, however, not possible to predict the individual fecundity in this group of infertile men by measuring the proportion of sperm heads, which remained stable after exposure to SDS or the proportion of zinc in the seminal fluid which was bound to Zn~L'IMW. The first split~ejaculate fraction should probably be studied instead of the whole mixed ejaculate to evaluate whether spermatozoa that tentatively enter the cervical mucus have an appropriate zinc~dependent stabilisation of their chromatin.
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