| 1. |
- Ahlqvist, Jan, 1952-
(författare)
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The temporomandibular joint : Tomopraphic and CT assesment of its bone demarcations with reference to adjacent organs
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The wall of the temporal bone separating the temporomandibular joint (TMJ) from surroundings organs, can be very thin and also have development defects. Distortion effects in the radiographic reproduction of these bone walls can result in misinterpretations when exanimating suspected pathologic changes in the region. These areas need to be radiographic identified prior to taking any invasive measures. Incorrect assessment of bone thickness may lead to serious sequelae due to the risk of penetration injury during invasive investigation or treatment of the TMJ or ear. The purpose of this project was to gain more detailed knowledge about the anatomy and topography of the TMJ with special reference to its bone demarcations regarding adjacent organs and to evaluate the tomographic and computed tomographic (CT) depiction of these bone walls. To obtain a basic analysis of the tissue anatomy and tomographic and CT reproduction of the TMJ region, autopsy specimens were studied. After CT and conventional tomography, the specimens were sectioned in a microtom. Three- dimensional orientation systems allowed identification of section depth in the radiograms and in the histologic sections, allowing the radiograms in turn to be correlated with the true anatomy. The angle of inclination relative to the perpendicular to established imaging planes the bone walls studied was examined in three projections in order to identify regions where the bone demarcation showed an unfavorable inclination regarding the possibility of valid radiographic representation. The thickness of the bone wall between the TMJ and the middle cranial fossa, measured in the thinnest part, varied between 0.08 and 3.62 mm, averaging 1.14 mm. The bone wall between the TMJ and the middle ear showed less variation in thickness ranging from 0.00 to 1.80 mm. The thickness of the bone wall separating the TMJ from the external auditory canal varied between 1.50 mm (lateral part) and 1.21 mm (central part), with a range of between 0.21 and 4.10 mm. Development defects of this bone wall were found in 5.2 % of the examined joints. The validity in tomographic depiction of these walls was highly dependent on an optimal orientation of the bone wall in relation to the image plane. The variations in the anatomy and sagittal dimension of the external auditory canal led to variations in tomographic blurring, and suggested the need for examinations after patient repositioning in cases of suspected bone resorbing lesions so that image aberration due to unfavorable inclination of the bone wall relative to the image plane may be excluded. CT of these bone walls was valid (± 10 %) for walls thicker than approximately 1 mm, forming an angle of less than 35® with the perpendicular to the scan plane when the bone wall thickness was determined as the full-width-at-half-maximum (FWHM). For bone walls thinner than 1 mm, and for those thicker than 1 mm and at an angle exceeding 35®, partial volume averaging effects resulted in a progressively increasing magnification of bone dimensions. Observer estimations of bone thickness from images obtained using conventional bone window settings (c=400, W=2000) showed good agreement for bone walls thicker than 1 mm and with an angle of inclination relative to the perpendicular to the image plane of less than approximately 25®. For bone walls thinner than 1 mm and for thicker than 1 mm with an inclination exceeding approximately 25®, the estimations resulted in a progressively increasing overestimation amounting 200% for gracile bone walls with an inclination of 45® to 50®. Determination of width or absence of the central white zone in images obtained with the described parameters could help to reduce the risk of overestimation of bone thickness. A considerable part of the bone walls separating the TMJ from the middle cranial fossa and the external auditory canal/middle ear, respectively, have dimensions and inclinations to established imaging planes used at TMJ examinations that make the depiction of these walls highly susceptible to image distortion.
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| 2. |
- Al-Taai, Nameer, 1975-
(författare)
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Dentoalveolar and craniofacial changes from early adolescence to late adulthood
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Study I: To evaluate the reliability and validity of different superimposition methods and to increase the precision with which craniofacial growth and treatment can be quantified. Study II: To explore the craniofacial changes that occur from early adolescence to late adulthood. Study III: To assess the impact of premolar extractions on dentoskeletal and facial morphologies up to late adulthood. Study IV: In a 50-year follow-up, to study how early extraction of four premolars affects the development of age-related lower incisor crowding. Materials and Methods: Study I: Forty pairs of cephalograms were analysed at mean ages of 9.9 (T1) and 15.0 (T2) years. Three superimposition methods were assessed: the Sella-Nasion (SN); the Tuberculum Sella-Wing (TW); and Björk’s structural. Björk’s structural method was performed using three techniques: direct, tracing template, and subtraction. Study II: Thirty subjects with a Class I normal occlusion and harmonious facial profile were investigated. Study data were obtained from cephalograms performed at 12 (T1), 15 (T2), 30 (T3), and 62 (T4) years of age. The craniofacial changes were assessed using superimposition-based and conventional cephalometric methods. Study III: Two groups were included. The Extraction group (N=30 with Class I crowding malocclusion) had their first premolars extracted at a mean age of 11.5 years, without subsequent orthodontic treatment. The Control group included 30 untreated subjects with Class I normal occlusion. Study data were obtained from cephalograms performed at 12 (T1), 15 (T2), 30 (T3) and 62 (T4) years of age. The dentoskeletal and soft tissue changes were assessed using superimposition-based and conventional cephalometric methods. Study IV: Two groups were included. The Extraction group (N=24 with Class I crowding malocclusion) that had their first premolars extracted at mean age of 11.5 years, without subsequent orthodontic treatment. The Control group included 21 untreated subjects with Class I normal occlusion. Study data were obtained from dental casts and cephalograms performed at mean ages of 11.4 and 13.0 years, for the two groups, respectively (T1), and at mean ages of 30.9 years (T2) and 61.7 years (T3).Results: Study I: The numerical data from the superimposition-based cephalometrics reflected a graphical illustration of superimposition and differed significantly from the data acquired using conventional cephalometrics. While there were no significant differences between the TW method and Björk’s three techniques, significant differences were found between the SN method and the other methods. Study II: The maxilla and mandible showed significant anterior growth from T1 to T2, and significant retrognathism from T3 to T4. The anterior facial height and jaw dimensions increased significantly until T3. From T3 to T4, significant posterior rotation of the mandible and opening of the vertical jaw relation were observed, in addition to significant retroclination of the upper incisors, decrease in lip prominence, and straightening of the facial profile. Study III: There were no significant differences between the Extraction and Control groups in terms of the skeletal sagittal relation, incisor inclination and protrusion (or for most of the soft tissue parameters) during the observation period. Study IV: The Extraction group showed significant improvement in the space deficiency of the lower teeth and no changes in the irregularity of the lower incisors up to late adulthood. In contrast, both the space deficiency of the lower teeth and irregularity of the lower incisors were significantly exacerbated in the Control group, up to late adulthood. Conclusions: The superimposition-based cephalometric method accurately generates numerical data for the craniofacial changes. Superimposition using the TW method is valid, reliable, and feasible, and is recommended to be used for superimposition-based cephalometrics. Moreover, craniofacial changes and development of lower incisor irregularity and crowding continue up to late adulthood in untreated subjects who were originally classified as having normal occlusion. For successful long-term outcomes, clinicians should therefore consider age-related changes in patients when planning for orthodontic, orthognathic, and prosthodontic treatments. Treatment with the extraction of four premolars alone in patients with Class I malocclusion with severe crowding does not impact the long-term dentoskeletal and soft tissue profile, and results in unchanged lower incisor alignment.
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| 3. |
- Belibasakis, Georgios N., 1976-
(författare)
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Cellular and molecular responses of periodontal connective tissue cells to Actinobacillus actinomycetemcomitans cytolethal distending toxin
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Actinobacillus actinomycetemcomitans is present in elevated proportions and numbers in dental bacterial biofilms of patients with localized aggressive periodontitis. This variant of periodontal disease, occurring in adolescents and young adults, is characterized by rapid and severe destruction of the connective tissues and bone supporting the teeth, eventually culminating in tooth loss. The cytolethal distending toxin (Cdt) is a newly discovered bacterial protein toxin, uniquely present in A. actinomycetemcomitans among all known to-date oral bacterial species. The Cdt has the capacity to inhibit mammalian cell growth, but its putative role in the pathogenesis of the disease is unclear. The aim of this in vitro work has been to study the effects of A. actinomycetemcomitans on periodontal connective tissue cell cultures, and to evaluate the possible involvement of its Cdt. A. actinomycetemcomitans inhibited the proliferation of gingival and periodontal ligament fibroblasts, as a result of a combined arrest at the G1 and G2/M phases of the cell cycle. This growth inhibition was non-lethal and the cells remained metabolically active, although their DNA synthesis was reduced. The intoxicated cells exhibited increased size and irregular structure, characterized by distension and elongation. This cellular enlargement occurred in both G1 and G2/M phase arrested cells. The Cdt of A. actinomycetemcomitans was responsible for the observed growth inhibition, as well as the concomitant morphological alterations. The possible induction of inflammatory cytokines related to bone resorption was investigated in response to A. actinomycetemcomitans, and the involvement of Cdt was evaluated. Extensive focus was given to the study of receptor activator of NF-κB ligand (RANKL) expression, a membrane-bound ligand that signals osteoclast progenitors to differentiate and fuse into mature osteoclasts, activating bone resorption. It was demonstrated that A. actinomycetemcomitans induced RANKL mRNA and protein expression in the cells studied, but did not affect the expression of its decoy receptor, osteoprotegerin. This induction was solely attributed to its Cdt, as demonstrated by the use of a cdt-knockout A. actinomycetemcomitans strain, purified recombinant Cdt, and antibodies blocking the Cdt. In addition, this event was not mediated by pro-inflammatory cytokines known to stimulate RANKL. Interleukin-6 mRNA and protein expression were also enhanced by A. actinomycetemcomitans, but Cdt had limited involvement in this enhancement. In conclusion, two distinct mechanisms by which A. actinomycetemcomitans Cdt may be involved in the pathogenesis of localized aggressive periodontitis are proposed. Firstly, the growth arrest of the resident fibroblasts may impair the physiological connective tissue remodelling equilibrium and lead to connective tissue attachment loss. Secondly, the induction of RANKL by these cells, residing in the proximity of the alveolar bone, may locally stimulate osteoclastogenesis and promote alveolar bone resorption. This work also provides further insights to the understanding of Cdt mechanisms of action, contributing to the global characterization of the toxin’s virulence.
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| 4. |
- Bergendal, Birgitta, 1947-
(författare)
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Oligodontia and ectodermal dysplasia : on signs, symptoms, genetics and outcomes of dental treatment
- 2010
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Ingår i: Swedish dental journal. Supplement. - Umeå : Umeå universitet. - 0348-6672. ; :205, s. 13-78
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this thesis was to broaden our knowledge of the signs and symptoms, genetics, and outcomes of dental implant treatment in individuals with oligodontia or ectodermal dysplasia. Article I is a population-based study in three Swedish counties of 162 individuals with oligodontia, which was a prevalence of 0.09%. The intent was to explore ways for dentists to assess symptoms from other ectodermal structures than teeth through a clinical interview and chair-side analyses. Thirty per cent had low salivary secretion rates while only 11% with no known syndrome reported symptoms from hair, nails, or sweat glands. These are, together with teeth, the ectodermal structures on which it is proposed that a clinical diagnosis of ectodermal dysplasia (ED) be based. Article II screened 93 probands with oligodontia for mutations in six genes known to cause oligodontia and hypohidrotic ED. Sequence alterations predicted to be damaging or potentially damaging were revealed in the AXIN2, MSX1, PAX9, and EDARADD genes in 14 (15%) of the probands. All mutations but one were novel. For the first time, EDARADD mutations were shown to cause isolated oligodontia. No individual who had reported ectodermal symptoms from hair, nails, or sweat glands had a mutation. Article III assessed orofacial function in individuals with different types of EDs using the Nordic Orofacial Test-Screening (NOT-S) protocol. Individuals with ED scored significantly higher in orofacial dysfunction than a healthy reference sample, especially in the Chewing and swallowing, Dryness of the mouth, and Speech domains. Article IV surveyed treatment outcome of dental implants in Swedish children up to age 16 years. In a 20-year period, only 26 patients were treated, 5 of whom had hypohidrotic ED and anodontia of the mandible. Individuals with ED had 64% failed implants compared to 6% among subjects with teeth missing due to trauma or agenesis. The main conclusions of this thesis were that (i) a check of whether one or more permanent incisors are missing will identify 65% of individuals with oligodontia and 84% of individuals missing nine teeth or more, (ii) evaluation of salivary secretion is indicated in children with oligodontia, (iii) a majority of individuals with oligodontia did not report other abnormal ectodermal organ function besides teeth, (iv) no clinical indicator discriminated between individuals with and without mutations in the tested genes, and more unidentified genes are involved in tooth morphogenesis, (v) EDARADD mutations are associated with isolated oligodontia, (vi) evaluation of orofacial function is indicated in individuals with ED, and many individuals with ED would benefit from orofacial skills training, (vii) dental implant placement is a rare treatment modality in children, (viii) individuals with hypohidrotic ED seem to present special challenges due to structural as well as direct effects of the mutations on bone, which seem to compromise osseointegration, (ix) central registers on signs and symptoms in individuals with rare disorders would help establish prevalences of various diagnoses and define treatment needs, and (x) quality registers for monitoring treatment outcomes of dental implants would promote early detection of risks and side-effects in individuals with rare disorders.
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| 5. |
- Bernhold Brechter, Anna, 1971-
(författare)
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Kinins : important regulators in inflammation induced bone resorption
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inflammatory processes in, or in close vicinity of, the skeleton often lead to loss of bone tissue. Different cytokines have been shown to be involved as stimulators of inflammatory induced osteoclastic bone resorption. During inflammatory processes also the kallikrein-kinin system is activated, leading to production of kinins that can cause pain, vasodilation and increased permeability of vessels. Kinins can also induce bone resorption in vitro. All cytokines and kinins that stimulate bone resorption stimulate in parallell prostaglandin synthesis, and prostaglandins, per se, have also been shown to induce bone resorption. The aim of this project was to increase the knowledge about the mechanisms involved in the interactions between different inflammatory mediators (i.e. kinins, cytokines and prostaglandins) suggested to be involved in the pathogenesis of inflammatory bone resorbing diseases. Human osteoblasts (MG-63) are equipped with both kinin B1 and B2 receptors linked to prostaglandin release and the stimulation of prostaglandin release are likely mediated via separate molecular mechanisms (Paper I). Activation of B1 or B2 receptors causes synergistic stimulation of PGE2 synthesis induced by either interleukin-1b (IL-1b) or tumour necrosis factor-a (TNF-a) (Paper II). The molecular mechanism involves increased expression of cyclooxygenase-2 (COX-2) and results in synergistic potentiation of receptor activator of NF-kB ligand (RANKL) protein expression. The synergistic interaction is dependent on the activation of NF-kB and the mitogen-activated protein kinases (MAPK) p38 and JNK (Paper II). The synergistic increase in RANKL expression might be an explanation why kinins potentiate IL-1b induced bone resorption, a mechanism likely to be important in inflammation induced bone resorption in diseases such as periodontal disease and rheumatoid arthritis. The synergism between kinins and IL-1b or TNF-a might also be dependent on regulation of kinin receptors, since both IL-1b and TNF-a markedly upregulated B1 and B2 receptors, both at the mRNA level and protein level (Paper III). This upregulation is not further potentiated by the kinins, and different kinin receptor agonists do not regulate the receptors for IL-1b or TNF-a, in MG-63 cells. No other cytokines known to stimulate bone resorption regulates the expressions of B1 and B2 receptors. The IL-1b- or TNF-a-induced enhancements of B1 and B2 receptor expressions involve activation of NF-kB and MAPK. The enhancement of kinin receptors may also be an important mechanism in the synergistic interactions between the two pro-inflammatory cytokines and kinins (paper III). IL-4 and IL-13 are two cytokines that have been shown to inhibit bone resorption. We have shown that COX-2 and both B1 and B2 receptors are down-regulated by IL-4 and IL-13, via a ‘signal transducer and activator of transcription6’ (STAT6) dependent pathway, which might be an important regulatory mechanism in inflammation induced bone resorption (paper IV). In conclusion, the mechanisms behind the synergistic potentiation of prostaglandin formation and increased bone resorption caused by co-stimulation with kinins and IL-1b or TNF-a seem to involve both potentiation of COX-2 and subsequently increased levels of RANKL, as well as upregulation of B1 and B2 kinin receptors. Interestingly, IL-4 and IL-13 decreased the expressions of COX-2 and both B1 and B2 receptors. These events might be important in the regulation of inflammation induced bone resorption in diseases such as periodontitis and rheumatoid arthritis.
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| 6. |
- Bodin, Ingrid, 1944-
(författare)
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Impairment of intra-oral sensation, discrimination ability, and swallowing function following radiotherapy and surgery for oral and pharyngeal cancer
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Oral and pharyngeal cancer is commonly treated with a combination of radiotherapy and surgery. It is a clinical knowledge that patients often experience severe swallowing disorders following treatment. Since surgical sequelae are instantaneous and obvious, little attention has been paid to other concurrent effects of the treatment. To shed light on this subject, the aim of this thesis was twofold (i) to make a retrospective inventory of the sequelae following treatment and (ii) to perform a prospective, inceptive examination at diagnosis, and to follow-up after radiotherapy, six months and 12 months after surgery. The files of ninety-nine patients revealed that following treatment one-third had to use gastric fistulas and more than nine of ten patients had restricted swallowing capacity. Every second patient could only swallow puréed or liquid food. Adequate intra-oral sensation and discrimination ability is essential for bolus preparation and bolus control, for appropriate elicitation of the swallowing reflex and, hence, for the oral phase of swallowing. At the inceptive examination, the prospective part of the study demonstrated intra-oral discrimination ability in patients was equal to that in healthy controls but was impaired six months after treatment and there was no significant improvement after 12 months. It had been expected that the patient’s healthy, non-tumor side would compensate but it did not. An explanation was found when it was revealed that radiotherapy induced a delayed decline in intra-oral sensation. Sensory decline was not demonstrated within a month after radiotherapy but was manifest six months later. Since the radiotherapy field includes the neck, because of the risk for metastasis, it is highly plausible that pharyngeal sensation declines in a manner corresponding to that found intra-orally when the healthy side is irradiated. In accord with this presumption, pharyngeal swallowing function deteriorated in patents with oral tumors. Cineradiographic evaluation of oral and pharyngeal swallowing function disclosed a significant association between the degree of swallowing dysfunction and the degree of sensory decline and with the degree of impairment of shape recognition. Conclusions: Delayed intra-oral sensory decline, found to be induced by radiotherapy, can be expected to appear in the entire radiation field, including the oral cavity and the pharynx, with adverse effect on swallowing. Testing intra-oral sensation close to the last radiotherapy session is not advisable, because sensory decline does not develop immediately after radiotherapy but manifests after six months. Spontaneous sensory rehabilitation cannot be expected after six months. The significant association between degree of swallowing dysfunction and degree of intra-oral sensory decline and impaired discrimination ability must be considered in the quest for functional rehabilitation of patients treated for oral or pharyngeal cancer.
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| 7. |
- Brundin, Malin, 1972-
(författare)
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Stability of bacterial DNA in relation to microbial detection in teeth
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The fate of DNA from dead cells is an important issue when interpreting results from root canal infections analysed by the PCR technique. DNA from dead bacterial cells is known to be detectable long time after cell death and its stability is dependent on many different factors. This work investigated factors found in the root canal that could affect the recovery of microbial DNA. In an ex vivo experiment, DNA from non-viable gram-positive Enterococcus faecalis was inoculated in instrumented root canals and recovery of DNA was assessed by PCR over a two-year period. DNA was still recoverable two years after cell death in 21/25 teeth. The fate of DNA from the gram-negative bacteria Fusobacterium nucleatum and the gram-positive Peptostreptococcus anaerobius was assessed in vitro. DNA from dead F. nucleatum and P. anaerobius could be detected by PCR six months post cell death even though it was clear that the DNA was released from the cells due to lost of cell wall integrity during the experimental period. The decomposition rate of extracellular DNA was compared to cell-bound and it was evident that DNA still located inside the bacterium was much less prone to decay than extracellular DNA.Free (extracellular) DNA is very prone to decay in a naked form. Binding to minerals is known to protect DNA from degradation. The fate of extracellular DNA was assessed after binding to ceramic hydroxyapatite and dentine. The data showed that free DNA, bound to these materials, was protected from spontaneous decay and from enzymatic decomposition by nucleases.The main conclusions from this thesis were: i) DNA from dead bacteria can be detected by PCR years after cell death ex vivo and in vitro. ii) Cell-bound DNA is less prone to decomposition than extracellular DNA. iii) DNA is released from the bacterium some time after cell death. iv) Extracellular DNA bound to hydroxyapatite or dentine is protected from spontaneous decomposition and enzymatic degradation.
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| 8. |
- Bryndahl, Fredrik, 1963-
(författare)
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Temporomandibular joint disk displacement and subsequent adverse mandibular growth : a radiographic, histologic and biomolecular experimental study
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The mandibular condyles represent important growth sites within the facial skeleton. Condylar growth is not a pacemaker of mandibular development, but it provides regional adaptive growth that is of considerable clinical significance, as the condyle’s upward and backward growth movement regulates the anteriorly and inferiorly directed displacement of the mandible as a whole.Orthopedic problems of the temporomandibular joint (TMJ), such as displacement of the TMJ disk, are common in the adolescent population. Clinical studies of mandibular asymmetry and mandibular retrognathia in adults as well as in children and adolescents, have reported an association with coexisting non-reducing displacement of the TMJ disk without identifying the cause and effect. Through experimental studies causality has been established, and unilateral affliction during growth has been shown to retard ipsilateral mandibular development with facial asymmetry as the sequel. It was hypothesized that bilateral non-reducing TMJ disk displacement during growth would impair mandibular development bilaterally, resulting in mandibular retrognathia. TMJ disk displacement has repeatedly been demonstrated to induce histological reactions of the condylar cartilage. An additional assumption was therefore that a non-deranged TMJ disk function is crucial for the maintenance of the growing condyle’s biophysical environment, and that a connection ought to exist between the amount of condylar cartilage changes caused by TMJ disk displacement and the amount of subsequent adverse mandibular growth. It was also hypothesized that non-reducing displacement of the TMJ disk in growing individuals would result in qualitative and quantitative changes of the condylar subchondral bone.An improved experimental cephalometric method was developed in order to optimize the reliability of longitudinal radiographic evaluation of fast growing small animals. Bilateral non-reducing TMJ disk displacement was surgically created in ten growing New Zealand White rabbits, with ten additional rabbits serving as a sham operated control group. The amount and direction of craniofacial growth was followed over time in serial cephalograms, aided by tantalum implants in the jaws. The study period was chosen to correspond to childhood and adolescence in man. The assessed growth of each side of the mandible was correlated to the histological feature of ipsilateral condylar cartilage at the end of the growth period. The amount and composition of subchondral bone from three regions of interest in the condyle, and the expression of local growth factors in the adjacent condylar cartilage was evaluated.The results verified that bilateral non-reducing TMJ disk displacement retarded mandibular growth bilaterally; the extent corresponding to mandibular retrognathia in man. Displacement of the TMJ disk during the growth period induced condylar cartilage adaptive reactions that were associated with both an adverse amount and direction of mandibular growth, manifesting in a retrognathic mandibular growth pattern. Growth impairment fluctuated over time, with the most striking retardation occurring during periods of increased general growth, implying a local growth reduction explicitly counteracting general hormonal growth acceleration. A significant decrease of the total amount of subchondral bone, in spite of a general increase of new bone formation in the experimental condyles, pointed to a reparative compensation for an extensive resorption of subchondral bone due to displacement of the TMJ disk, but not to the extent that normal growth would be maintained. These results constitute an explanation for the adverse mandibular development following non-reducing TMJ disk displacement in growing individuals.This project has shown that non-reducing displacement of the TMJ disk during growth has significant consequences on facial development. The findings strongly advocate early and accurate diagnosis and treatment of TMJ disk displacement in the adolescent population, thereby presumably reducing the need for future orthodontic and surgical craniofacial corrective therapy. The results furthermore enhance the need for full appraisal of TMJ disk function in the adolescent population during orthodontic functional therapy, as the condylar cartilage and subchondral bone reactions to a concomitantly displaced non-reducing TMJ disk must be expected to interfere with the intended growth stimulating treatment. The findings of intact articular layers in spite of gross histological and morphological soft and hard tissue changes as a sequel to TMJ disk displacement in growing individuals, implicate a clinical risk of false positive radiographic diagnosis of degenerative changes of the TMJ in children and adolescents.
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| 9. |
- Cricchio, Giovanni, 1968-
(författare)
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On guided bone reformation in the maxillary sinus to enable placement and integration of endosseous implants. Clinical and experimental studies.
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dental caries and periodontal disease are the major causes for tooth loss. While dental caries commonly involve the posterior teeth in both jaws, the teeth most commonly lost due to periodontal problems are the first and second molars in the maxilla. As a consequence, the upper posterior jaw is frequently edentulous. Implant therapy today is a predictable treatment modality for prosthetic reconstruction of edentulous patient. Insufficient amounts of bone, due to atrophy following loss of teeth or due to the presence of the maxillary sinus, can make it impossible to insert implants in the posterior maxilla. During the 1970s and 1980s, Tatum, Boyne and James and Wood and Moore first described maxillary sinus floor augmentation whereby, after the creation of a lateral access point, autologous bone grafts are inserted to increase crestal bone height and to create the necessary conditions for the insertion of implants. This surgical procedure requires a two-stage approach and a double surgical site: first, bone is harvested from a donor site and transplanted to the recipient site; then, after a proper healing period of between 4 to 6 months, the implants are inserted. This kind of bone reconstruction, even if well documented, has its limitations, not least in the creation of two different surgical sites and the consequent increased risk of morbidity. In 2004, Lundgren et al. described a new, simplified technique for the elevation of the sinus floor. The authors showed that by lifting the sinus membrane an empty space was created in which blood clot formations resulted in the establishment of new bone. The implants were placed simultaneously to function as “tent poles”, thus maintaining the sinus membrane in a raised position during the subsequent healing period. An essential prerequisite of this technique is to obtain optimal primary implant stability from the residual bone in the sinus floor. An extremely resorbed maxillary sinus floor, with, for example, less than 2-3 mm of poor quality residual bone, could impair implant insertion. The aims of the present research project were (i) to evaluate the donor site morbidity and the acceptance level of patients when a bone graft is harvested from the anterior iliac crest, (ii) to evaluate implant stability, new bone formation inside the maxillary sinus and marginal bone resorption around the implants in long term follow up when maxillary sinus floor augmentation is performed through sinus membrane elevation and without the addition of any grafting material, (iii) to investigate new bone formation inside the maxillary sinus, in experimental design, using a resorbable space-maker device in order to maintain elevation of the sinus membrane where there is too little bone to insert implants with good primary stability. In Paper I, 70 consecutively treated patients were retrospectively evaluated in terms of postoperative donor site morbidity and donor site complications. With regard to donor site morbidity, 74% of patients were free of pain within 3 weeks, whereas 26% had a prolonged period of pain lasting from a few weeks to several months. For 11% of patients there was still some pain or discomfort 2 years after the grafting surgery. Nevertheless, patients acceptance was high and treatment significantly improved oral function, facial appearance, and recreation/social activities and resulted in an overall improvement in the quality of life of formerly edentulous patients. In Paper I and III, some differently shaped space-making devices were tested on primates (tufted capuchin - Cebus apella) in two experimental models aimed at evaluating whether a two-stage procedure for sinus floor augmentation could benefit from the use of a space-making device to increase the bone volume and enable later implant installation with good primary stability, without the use of any grafting material. An histological examination of the specimens showed that it is possible to obtain bone formation in contact with both the Schneiderian membrane and the device. In most cases the device was displaced. The process of bone formation indicated that this technique is potentially useful for two-stage sinus floor augmentation. The lack of device stability within the sinus requires further improvement in space-makers if predictable bone augmentation is to be achieved. In Paper IV, a total of 84 patients were subjected to 96 membrane elevation procedures and the simultaneous placement of 239 implants. Changes of intra-sinus and marginal bone height in relation to the implants were measured in intraoral radiographs carried out during insertion after 6 months of healing, after 6 months of loading and then annually. Computerised tomography was performed pre-surgically and 6 months post-surgically. Resonance frequency analysis measurements were performed at the time of implant placement, at abutment connection and after 6 months of loading. The implant follow-up period ranged from a minimum of one to a maximum of 6 years after implant loading. All implants were stable after 6 months of healing. A total of three implants were lost during the follow-up period giving a survival rate of 98.7%. Radiography demonstrated an average of 5.3 ± 2.1 mm of intra-sinus new bone formation after 6 months of healing. RFA measurements showed adequate primary stability (implant stability quotient 67.4 ± 6.1) and small changes over time. In conclusion, harvesting bone from the iliac crest could result in temporary donor site morbidity, but in 11% of patients pain or discomfort was still present up to 2 years after surgery. However, patient satisfaction was good despite this slow or incomplete recovery, as showed by the quality of life questionnaire. Maxillary sinus membrane elevation without the use of bone grafts or bone substitutes results in predictable bone formation both in animal design, where the sinus membrane is supported by a resorbable device, and in clinical conditions, where the membrane is kept in the upper position by dental implants. This new bone formation is accompanied by a high implant survival rate of 98.7% over a follow-up period of up to 6 years. Intra-sinus bone formation remained stable in the long-term follow-up. It is suggested that the secluded compartment allowed bone formation in accordance with the principle of guided tissue regeneration. This technique reduces the risks of morbidity related to bone graft harvesting and eliminates the costs of grafting materials.
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| 10. |
- Danielsson, Karin
(författare)
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Oral lichen planus : studies of factors involved in differentiation, epithelial mesenchymal transition and inflammation
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Lichen planus is a chronic inflammation of skin and mucosa with unknown cause. Oral Lichen Planus, OLP, affects around 2% of the population. Autoimmunity has been suggested as a possible cause as the disease has autoimmune features such as female predominance, cyclic nature and cytotoxic T-cell infiltrate. It has been suggested that the intense inflammatory response seen in OLP is caused by factors on the keratinocyte surface triggering the immune system. Chronic inflammation is one of the hallmarks of oral lichen planus and chronic inflammation is connected to increased risk of tumor development. WHO classifies OLP as a potentially malignant condition with increased risk of developing Squamous cell carcinoma of head and neck, SCCHN, but malignant transformation of OLP is a matter of controversy. The aim of these studies was to further elucidate the autoimmune and premalignant character of OLP. Factors involved in malignant transformation, autoimmunity and inflammation were analyzed in normal oral mucosa, OLP and SCCHN. Factors studied were the signal transducers of Transforming growth factor-β the Smad proteins, microRNAs, COX-2, the receptor CXCR-3 and its ligands CXCL-10 and -11 and ELF-3. Material and methods: In the study on Smad protein expression formalin fixed and paraffin embedded biopsies from normal oral mucosa, OLP and SCCHN was used. For the remaining studies fresh frozen biopsies from OLP and normal controls was used. All of the fresh frozen OLP samples and their controls were micro dissected to be able to analyze the epithelial part only as well as sections of the whole biopsy. Methods used are immunohistochemistry, qRT-PCR and Western blot. Results: Analyses of smad proteins expression showed a clear increase of smad3 and smad7 in OLP compared to normal oral mucosa. The expressions of smad proteins in the tumors were more heterogeneous. Some of the SCCHN samples showed a similar expression as OLP while others did not. Micro RNA analyzes showed that miR-21 and miR-203 was significantly increased in OLP epithelium compared to normal oral epithelium while the expression of miR-125b and their potential targets p53 and p63 was decreased in OLP. The presence of COX-2 was significantly higher in OLP than normal controls. At the same time the expression of miR-26b, a suggested repressor of COX-2 was decreased in OLP compared to normal mucosa. The receptor CXCR-3 and its ligands CXCL-10 and -11 were increased in OLP. Expressions of the differentiation involved factor ELF-3 mRNA as well as protein were decreased in OLP. Conclusion: The factors studied are involved in differentiation, malignant transformation and inflammation. Some of the results in these studies indicate a similar expression pattern for OLP and SCCHN. Several of the factors studied are involved in differentiation and their deregulation suggests a disturbed differentiation pattern and this could indicate a premalignant character of OLP but malignant transformation of OLP lesions are relative rare. A lot of these factors are also involved in inflammatory processes and connected to autoimmune diseases and their deregulation in OLP could also support an autoimmune cause of the disease. Based on our studies a suggestion is that the disturbed differentiation pattern triggers the intense immune response directed against the epithelial cells seen in OLP.
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