| 31. |
- Lundberg, Magnus
(författare)
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Traumatic isolated rupture of the knee medial collateral ligament : diagnosis and long term effects
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Isolated partial rupture of the knee medial collateral ligament (MCL) is the most common traumatic knee ligament injury. Owing to the good short- and medium-term functional results after conservative treatment, this injury has been regarded as harmless. The outcome after combination injuries, with simultaneous rupture of the anterior cruciate ligament (ACL), is more uncertain.The main purpose of this investigation was to improve the diagnosis of MCL injury and of concomitant injuries in acute knee trauma, in order to differentiate between the long-term effects of isolated and combined MCL injuries on knee function, sports participation, knee biomechanics and the development of secondary changes in articular cartilage and subchondral bone.Magnetic resonance imaging (MRI) was used with the aim to replace arthroscopy in the diagnosis of acute knee injuries with hemarthrosis. In patients, knee function and stability were assessed 4 years following conservative treatment of isolated partial MCL injury, thus evaluating any residual biomechanical abnormalities that could influence the long-term prognosis. Further, the 10-year outcome after isolated partial MCL injury and combined MCL/ACL injuries was evaluated with special reference to knee performance, knee stability and the development of radiographic arthrosis. Secondary changes to articular cartilage and bone were further evaluated with MRI and analysis of proteoglycan fragment concentrations in joint fluid. Finally, the effects of removal of the MCL during postnatal growth on rat knee joint development were studied with special reference to bone apposition and cartilage changes.Because of the low diagnostic accuracy for significant meniscal tears, MRI was not as reliable as arthroscopy for the diagnosis and screening of acute knee injuries. However, MRI was found to be superior to weight-bearing radiography and chemical analysis of joint fluid in the detection, staging, localisation and sizing of early articular cartilage changes in the knee joint.In a 10-year perspective, partial MCL injury lead to a small, permanent increase in valgus rotation and decrease in initial valgus stiffness of the knee joint, but knee function and sporting performance were excellent. In 13% of the cases subtle radiographic changes (Fairbank signs) were present. Combined MCL/ACL injuries had a similarly good long-term functional outcome, in spite of a higher number of reinjuries, increased sagittal knee translation, and a higher incidence of subtle radiographic arthrosis (50%) than after an isolated injury. The animal experiment further suggested that a loss of the MCL during growth alters the bony development of the knee joint.
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| 32. |
- Niklasson, Magnus
(författare)
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The vestibular system, a tool to study neurotoxicants in the central nervous system
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The vestibular and opto-ocular motor (VOOM) system in pigmented rats was investigated. Horizontal eye movements were recorded by the magnetic search coil technique during different kind of stimulations. The dynamics of the vestibular ocular reflex (VOR) and the optokinetic reflex (OKR) as well as the interaction of the two rel1exes were analysed. The ability to cancel nystagmus during vestibular and optokinetic stimulation was found to be comparable to "higher" animals.The experimental model was used to study the effects of toxicants and drugs on the VOOM system. Four different solvents, known to cause disturbances of the central nervous system (CNS), were tested. Acute exposure by inhalation of each solvent gave specific dose-response related effects in the VOOM system, most of which could be explained by an alteration of the cerebellar-vestibular circuit. However there were differences among the four solvents, the results indicating that different solvents should be considered as individual substances in toxicological CNS research.The effects of drugs, related to GABAB-transmission, were investigated.Baclofen, a GABAB-agonist, affected the VOR, the OKR and the interaction of these two in a dose-related way. All these effects could be blocked by CGP 35348, a GABAB-antagonist.The similarities in the effects of baclofen to the effects of toluene were striking. It was demonstrated that effects of toluene on the VOR could be blocked by CGP 35348 at a dose which did not cause any effects per se. It was concluded that some of the effects of toluene on the VOOM system were related to GABA-transmission, directly or indirectly.The VOOM system was also used in an otoneurological test battery to investigate the effects on the CNS in workers, long-term exposed to solvents. Dynamic posturography was also performed to obtain an indication of the integration of somatosensory, visual, and vestibular stimuli in the equilibrium system. Reduced ability to visual suppression, prolonged latency of saccades and pathology in the posturography tests were found in the solvent exposed group compared to results of a non-exposed healthy control group.All exposed worker had been evaluated for a possible chronic toxic encephalopathy (CTE) and were categorized in three groups non-CTE, incipient CTE, and CTE. These categories, based on psychometric test results and case histories of exposure and symptoms, were poorly correlated to the otoneurological findings. Even in the non-CTE group pathological findings were present. Lesions in the CNS revealed by an otoneurological investigation were apparently not found in the neuropsychological investigation. This indicates that an otoncurological test battery could contribute valuable information in the evaluation of long-term solvent exposed people suspected for CTE.The studies related above, demonstrate that the VOOM system is an useful tool in evaluating toxicological effects in the CNS.
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| 33. |
- Nybom, Pia
(författare)
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On the Regulation of the Epithelial Paracellular Permeability
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The epithelia of for instance the small intestine(s) plays a crucial role in the vectorial transport of nutrients and other solutes from the lumen to underlying body fluids, i.e. blood and lymph. However, the epithelial cells are also important in the formation and maintenance of a barrier towards harmful food components and toxic bacterial products. The research presented in this thesis aimed at further understanding theregulation of the paracellular permeability barrier in epithelia, especially in relation to structural modifications of the epithelial actin cytoskeleton and to intracellular signals. In particular, the objectives of the study were to: i) assess the associationbetween tight junctional integrity and the cytoskeleton by using cytochalasin B and dihydrocytochalasin B as modifying agents, ii) examine the involvement of phospho-inositide turnover in modulation of the paracellular barrier and the organization of the actin cytoskeleton, iii) investigate the participation of protein kinase C in the regulation of tight junctional integrity, iv) elucidate changes in the tight junction function andstructure caused by enterotoxigenic Vibrio cholerae, and v) examine the role of nitric oxide in the formation and regulation of the permeability barrier. To summarize, cytochalasin B and dihydrocytochalasin B mediate specific and dose-dependent effects on the transepithelial electrical resistance of MDCK-I epithelial cells. Furthermore, these alterations correlate well with distinct changes in the organization of filamentous actin and the tight junction-associated protein, Z0-1. Moreover, the actin-associated modulation of the epithelial barrier function appears to be dependent on phosphoinositide (PI) turnover, as elucidated by the combined effects of the PI 3-k:inase inhibitor, wortmannin, and dihydrocytochalasin B. The activation of protein kinase C with phorbol ester causes distinct changes in the transepithelial resistance and tight junction structure of MDCK-I and HT-29 cells. In addition, tight junctional function and structure also seem to be modulated by nitric oxide. A "new toxin", the hemagglutinin/protease (HNprotease) of Vibrio cho!erae was identified in the growth medium of a toxin-attenuated strain. The HA/protease causes characteristic alterations of the epithelial structure and barrier function, which were reduced in the presence of nitric oxide.
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| 34. |
- Singh, Ashok Kumar
(författare)
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Global EDS information support for local MCHC activity with emphasis on immunisation and evaluation
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This research, in the field of Medical Informatics within a defined sector of Primary Health Care services, namely, Maternal and Child Health Care (MCHC) is a realisation, implementation and evaluation of the WHO motto "Think globally, act locally". It has been conducted in three distinct phases. The first phase involved the design and development of an application software in the MCHC domain, The applicable Essential Data Set (EDS) was established after an analysis of the literature and Indian and the Swedish Maternal Health records (I), which also showed deficiencies in the existing documentation, pointing at a general need in both external audit and internal quality improvement for the MCHC application software (II). The MCHC software was developed and tested for microcomputer implementation, suitable for peripheral use in developing countries (Ill). The second phase comprised of the pilot implementation of the system at a number of sites in India and in particular at Bhorugram, a village in the Thar desert of Rajas than State of India (IV), where the application software was permanently installed and tested for clinical use (V). Cost-effectiveness of the information system is demonstrated through an economic evaluation of the project using a local quality indicator comprised by the immunisation subprogram, in particular the Fully Immunised Child (FIC) (VI). The third phase of the study was the performance evaluation of the information system after four years of constant use (VII). This had been successful in all operational terms, and the F1C index could be used as a local cardinal index to monitor and evaluate the quality of care, cost-effectiveness and community participation of the Information system, MCHS. Health Systems and Health Economy Research alike have long searched for apt quality and performance markers that in themselves could embrace and express a number of aspects and factors. The FIC index isshown to well meet the criteria of such a cardinal measure in the MCHC services, and the inferences to the value of the information system are comparatively straightforward. Participation and compliance improved asreflected in a markedly decreased drop-out frequency. These results could be extrapolated to the larger, even the global, scale.
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| 35. |
- Vavruch, Ludek
(författare)
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DNA content, proliferation markers and histopathology as prognostic factors in Astrocytic tumours
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The DNA index and S-phase fractions obtained from freshly frozen and paraffin-embedded specimens of 49 primary intracranial tumors showed significant correlation. Very similar results were obtained when a subgroup of astrocytomas was analyzed. Thus, the feasibility of DNA-flow cytometry for retrospective studies of archival tumor specimens was confirmed. In a study of 134 astrocytomas a strong correlation between grade of malignancy, S-phase fraction and DNA ploidy type was seen. In multivariate Cox regression analysis of 60 cases with grade II or Ill astrocytomas, age, grade of malignancy, DNA ploidy and S-phase were independent prognostic factors. An age of under 50, grade II, low S-phase and tetraploid DNA pattern correlated with long survival. Twenty-two recurrent astrocytomas were investigated after primary and repeated surgery. The grade of malignancy had significantly increased at the time of re-operation. The S-phase also tended to increase while the DNA-index was essentially unchanged. In recurrent astrocytomas the original_grade of malignancy was the most important prognostic parameter, which significantly correlated with time to recurrence and with survival after reoperation. The recurrence-free interval was significantly shorter in patients over 50 years of age and patients with an aneuploid DNA pattern at the time of the first surgery. However, when DNA ploidy, histopathological grade and age were evaluated simultaneously in a multivariale analysis, DNA ploidy was not an independent prognostic indicator. A strong correlation was found between the cell replication measured as Ki-67 labeling index and grades of malignancy at primary and repealed surgery. When less than 10 percent of cells were stained by Ki-67 after primary surgery, patient survival was prolonged approximately three times compared to survival of patients with a high Ki-67 labeling index.
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| 36. |
- Öberg, Ulrika
(författare)
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Functional assessment system of lower-extremity dysfunction
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Functional Assessment System (FAS) is a new instrument for evaluation of lower-extremity dysfunction. It consists of 20 variables, representing major lower--extremity functions related to daily life activities. The variables are divided into five groups: hip impairment, knee impairment, physical disability, social disability, and paiu variables. The grouping agrees fairly well with the WHO classification of impairment, disabilities and handicaps. Every variable is given a disability score on a five-point scale. The scores are plotted into a diagram, giving an individual functional profile. The profile can be used to document present functional status, for goal-setting, and for follow-up after treatment. It can also be used to design individual training programs.The aim of this thesis was:• to present the new Functional Assessment System (FAS)• to examine the metric properties of the FAS, and• to apply the FAS in some clinical situations.The FAS was applied on a series of patients with osteoarthritis of the hip or knee. Content validity was tested with factor analysis. The obtained factor structure agreed very well with the preliminary grouping of the variables. Concurrent validity was tested by comparison with measurements from the AIMS (Arthritis Impact Measurement Scales), the Rosser-Kind index (for evaluation of quality of life), and a radiographic scale for grading of osteoarthritis. There was a good agreement between the measurements of the FAS and the physical variables of the AIMS. There was also a good agreement between the FAS and the results obtained by the Rosser-Kind index. There was a low agreement between the FAS and the psychosocial variables of the AIMS. There was also a low correlation between the radiographic grading of osteoarthritis and the functional status recorded with the FAS. Inter-tester reliability was evaluated as correlation between the measurements performed by two independent physiotherapists. There was an almost perfect agreement between the two testers. The FAS was also tested for discriminatory power. It showed a good ability to differentiate between healthy subjects and patients with osteoarthritis. It also had a good power to discriminate between different degrees of the disease. The disability group of variables had better discriminstory power than the impairment group of variables. Most variables had a high specificity, whereas high sensitivity was mainly found in the disability group of variables and pain. The FAS was used to measure outcome after arthroplasty. A baseline functional status was recorded before surgery, and a goal profile was made. Six months later there was a striking improvement, especially in the disability variables and pain, and there was a high degree of goal achievement of most patients in most variables. Patients admitted for arthroplasty were examined for age-related diffirences in founctional status, Despite the fact that age was not included in the criteria for operation, old people had significantly lower functional status. This finding may indicate a hidden age criterion for referral of patients for arthroplasty. The age-related changes were mainly found in the disability group of variables. These findings may speak in favor of early surgery of patients with osteoarthritis.To summarize: The FAS had very good metric properties, such as validity, intertester reliability, discriminatory power, sensitivity and specificity. It was also a useful instrument in a clinical setting to record functional status, to set an individual treatment goal, and as an instrument for follow-up and outcome measurements. It was also sensitive in detecting age-related differences in patients admitted for arthroplasty. It can be used to communicate functional status to other health professionals, and to establish realistic goals for the patient.
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