Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Sydney, 2008. / Title from title screen (viewed Mar. 12, 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Discipline of Medicine, Faculty of Medicine. Degree awarded 2008; thesis submitted 2007. Includes bibliography. Also issued in print.

L’odontogenèse est sous contrôle génétique strict et elle est contrôlée par des interactions épithelio-mésenchymateuses. Les anomalies bucco-dentaires sont un des signes cliniques des syndromes. Parmi 7000 syndromes connus 900 ont un phénotype oral. Ce travail combine l’étude de modèles animaux et la bioinformatique pour améliorer la compréhension des mécanismes étiopathogéniques impliqués dans le développement dentaire.Méthodes :(1)Sélection de gènes impliqués dans des syndromes dont l’expression n’est pas caractérisée ; (2)Identification de gènes candidats par analyse de leur expression crânio-faciale et dentaire (atlas de transcriptome EURExpress) ; (3)Sélection de gènes différenciellement exprimés entre molaires et incisives et entre molaires mandibulaires et maxillaires au stade E14.5 par analyse transcriptomique ; (4)Etude par microtomodensitométrie des malformations crânio-faciales et bucco-dentaires des souris Rsk2-/Y (modèle du syndrome de Coffin-Lowry). Résultats : (1)Patrons d’expression au cours du développement dentaire pour 13 gènes ; (2)Patrons d’expression pour 4 gènes (3)88 gènes différenciellement exprimés entre molaires mandibulaires et incisives et 53 entre molaires mandibulaires et maxillaires (4)Taille réduite des mutants, déviation nasale et présence de dents surnuméraires. Conclusion : Ce projet fédère des scientifiques et des cliniciens autour de la compréhension des anomalies bucco-dentaires afin de stimuler le diagnostic de ces troubles du développement en se basant sur des preuves scientifiques et de proposer de nouvelles options thérapeutiques. / Tooth development is under strict genetic control and is mediated by epithelio-mesenchymal interactions. Oro-dental anomalies are one aspect of the 7000 known syndromes and 900 of these have an oral phenotype. Our goal is to combine the study of animal models and bioinformatics to improve the understanding of etiopathogenic mechanisms involved in oral development. Methods: (1)Selection of known genes responsible for syndromes but for which the expression and/or roles are not characterised ; (2)Identification of new candidate genes, through an analysis of their craniofacial and dental expression patterns using the EURExpress mouse transcriptome-wide atlas ; (3)Selection of genes differentially expressed between molars and incisors and between mandibular and maxillary molars at E14.5 by transcriptomic analysis ; (4)Study of craniofacial and orodental malformations of Rsk2-/Y mice by microtomodensitometry (model of Coffin-Lowry syndrome) Results: (1)Expression pattern during odontogenesis for 13 genes ; (2)Expression pattern for 4 genes (3)88 gènes différentially expressed between molars and incisors and 53 between mandibular and maxillary molars (4)Smaller mutants, nasal deviation and supplementary teeth. Conclusion: This project federates scientists and clinicians around the understanding of orodental anomalies and should stimulate the implementation of science based evidence diagnosis and new therapeutic options.

M.Tech. (Chiropractic) / Purpose: The aim of this comparative study was to compare the effects of Muscle Energy Technique (MET) versus myofascial dry needling of quadratus lumborum in the treatment of myofascial trigger points (TrPs), with regards to pain, disability and lumbar spine range of motion. Method: Thirty participants, male and female between the ages of eighteen and forty-five years, with an active quadratus lumborum TrP were used in this study. The thirty participants were randomly divided into two groups consisting of fifteen individuals each, ensuring equal male to female and age ratios. Group 1 received treatment in the form of MET. Group 2 received treatment in the form of myofascial dry needling. The trial consisted of five visits over a treatment period of two weeks, of which the first four visits the participants received treatment and the fifth visit served the purpose of obtaining the final data. The data was gathered on the first, third and fifth visits. The data was gathered before the treatment was performed. Objective data consisted of measuring lumbar spine range of motion with a digital inclinometer and pain pressure threshold using an algometer. Subjective data was obtained by using the Numerical Pain Rating Scale (NPRS) and Oswestry Disablity Index for Lower Back Pain (ODI). Results: The results were interpreted by STATKON at the University of Johannesburg. Both groups improved significantly in both the objective and subjective measurements over the two week trial period. This indicted that both treatment interventions were effective in the treatment of active quadratus lumborum TrPs. The results also indicated that group 2 (myofascial dry needling) was statistically superior to group 1 (MET) with regards to the subjective and lumbar spine range of motion measurements obtained during the study. There was no statistical superiority between the two treatment interventions with regards to the pain pressure threshold values obtained. These results indicate that dry needling is more effective than MET in decreasing pain and disability, while increasing lumbar spine range motion due to active quadratus lumborum TrPs. Conclusion: It was concluded, based on the results, that myofascial dry needling was more effective than MET with regards to the subjective pain, disability and lumbar spine range of motion. However with regards to pain pressure threshold values, there was no superiority of either treatment. This study suggests that myofascial dry needling is a preferential treatment option than MET in the case of active quadratus lumborum TrPs as it is possible that dry needling alone is more effective in reducing pain, disability and increasing lumbar spine range of motion. However this does not rule out MET as treatment for active TrPs as objectively MET reduces objective pain as effectively as dry needling.

Bien que l’hétérogénéité des désordres génétiques nous limite dans l’identification du gène causal avec les approches diagnostiques conventionnelles, le séquençage de l’exome a permis d’accroitre le nombre de diagnostics moléculaires posés récemment. Par contre, le grand nombre de variants identifiés par cette méthode pose un défi significatif dans l’interprétation clinique de ses variants. Nous avons donc élaboré PhenoVar, un logiciel qui intègre les données phénotypiques et génotypiques pour retourner une courte liste de diagnostics potentiels. Nous voulons valider cette approche par phénotype au niveau clinique et montrer qu’elle peut être efficace pour diagnostiquer des patients atteints de maladies génétiques rares. Pour ce faire, le séquençage de l’exome a été effectué sur une cohorte de 51 patients. Ceux-ci présentent des dysmorphismes avec ou sans désordres neurodéveloppementaux dont l’étiologie reste indéterminée après plusieurs analyses conventionnelles. Suite au séquençage de l’exome, un pipeline d’analyse bio-informatique nous a permis de filtrer les variations pour garder seulement les variations rares, codantes, ayant une bonne qualité et pour éliminer les artéfacts de séquençage. Ensuite, pour analyser ces variations filtrées, une analyse manuelle et une analyse avec PhenoVar ont été faites. L’analyse manuelle consiste à regarder manuellement chaque variation pour voir son impact et identifier le diagnostic, sans regarder le phénotype du patient. Puis, Exomiser, un autre logiciel utilisant le phénotype, a été utilisé pour comparer les performances de PhenoVar. En comparaison avec l’analyse manuelle, PhenoVar nous a permis de diminuer de six fois le temps d’analyse et de diminuer de moitié le nombre de diagnostics potentiels. Avec ces deux méthodes, nous avons pu trouver le diagnostic moléculaire de 18 patients, soit un rendement diagnostic de 35%. Il est à noter qu’un diagnostic a été manqué par PhenoVar. Cependant, ce diagnostic a été récupéré en enlevant un filtre au niveau du phénotype. De plus, parmi les diagnostics effectués, 16 (89%) se retrouvent dans les dix premiers rangs de PhenoVar, tandis que seulement 10 (56%) se retrouvent dans les dix premiers rangs d’Exomiser. En conclusion, PhenoVar est supérieur à Exomiser pour trouver un diagnostic dans les dix premiers rangs. De plus, il se compare à l’analyse manuelle tout en diminuant le temps d’analyse et le nombre de variants. / Abstract: Although the heterogeneity of genetic disorders limits our capacity to identify the causal gene with conventional approaches, exome sequencing has increased the diagnostic yield. However, the large number of variants identified by this method poses a significant challenge in their clinical interpretation. Thus, we developed PhenoVar: a software that integrates phenotypic and genotypic data and produces a short list of potential diagnoses. The objective of this study is to validate this phenotype-based approach on a clinical level and show that it can be efficient to diagnose patients with rare genetic disorders. Exome sequencing was performed on a cohort of 51 patients. These presented with dysmorphic features with or without neurodevelopmental disorders of undetermined etiology, following conventional analysis. Following exome sequencing, a bioinformatics pipeline allowed us to filter variations, keeping only rare coding variations harboring high quality. Then, we analysed these filtered variations with both manual analysis and PhenoVar. In the manual analysis each variant was manually examined to determine its impact and to identify the diagnosis without taking the patient’s phenotype into consideration. Then, Exomiser, another phenotype-based tool, was used to compare PhenoVar’s performances. In comparison to the manual analysis, PhenoVar has allowed us to reduce the analysis time by six-fold and to reduce by half the number of potential diagnoses. With both methods, we found the molecular diagnosis in 18 patients; a rate of 35%. Moreover, among these diagnoses, 16 (89%) are found in the top 10 ranks of PhenoVar, compared to only 10 (56%) for Exomiser. In conclusion, PhenoVar proved to Exomiser in prioritizing the correct diagnosis in the top 10 ranks. Finally, diagnostic yield of PhenoVar is comparable to the manual analysis while reducing the analysis time and the number of variants.

Thesis (M.Tech.: Chiropractic)-Dept. of Chiropractic, Durban Institute of Technology, 2003 xv, 102 leaves / The purpose of this study was to determine the relative effectiveness of TENS electrodryneedling as compared to single dry needle insertion in the treatment of Myofascial Pain Syndrome.

Thesis (M.Tech.: Chiropractic) - Dept. of Chiropractic, Durban Institute of Technology, 2003 1 v. (various pagings) / Headaches are one of the most common clinical problems in medicine (Edwards et al. 1995). It is estimated that one in three people suffer from headaches at some stage in their life (Kim et al. 1995). It is an extremely common complaint in the industrialized world (Nilsson, 1997) and has a significant impact on employee absenteeism, productivity and quality of life (Schwartz et al. 1997). In the United States more than 15 000 tons of Aspirin is consumed annually for the relief of headaches, and the cost of evaluation and treatment of headache patients consumes millions of dollars a year (Bernat and Vincent, 1993). Tension - type headache is the commonest form of headaches (Edwards et al. 1995). It is a highly prevalent condition experienced annually by 30 - 70% of the population, and as a chief complaint, it constitutes 5 - 8% of Chiropractic patients (Vernon and McDermaid, 1998). It is divided into an Episodic and Chronic form (IHS, 1991:29), with Episodic Tension-type headache being far more prevalent than Chronic Tension-type headache (Schwartz et al. 1998). Episodic Tension-type headache is further subdivided according to the presence or absence of a muscular factor. According to the International Headache Society (1991:29) for decades a dispute has prevailed concerning the importance of muscle contraction in the pathogenesis of the headache, but conclusive studies are still lacking (IHS, 1991:29). Based on the IHS (1991:29) classification that tension-type headache is associated with a muscular component, the purpose of this study was to investigate the effect of specific myofascial trigger point therapy in the clinical presentation of Episodic Tension-type headache.

Thesis (M.Tech.: Chiropractic) -Dept. of Chiropractic, Durban Institute of Technology, 2003. xix, 199 leaves / The purpose of this study was to investigate the role of Myofascial Trigger Points of the quadriceps femoris muscle in the clinical presentation of Patellofemoral Pain syndrome. Patellofemoral Pain Syndrome according to current literature suggests an extensor mechanism dysfunction as the most probable etiology, however this syndrome has posed many unsolved mysteries and challenges to the medical community and remains a difficult condition to treat. Myofascial pain syndrome in contrast to this is a regional muscular disorder that results from myofascial trigger points within the muscle. The presence of these trigger points could result in anterior knee pain, imbalance of the extensor mechanism and instability of the patellofemoral joint, which could present as a Patellofemoral Pain Syndrome.

Thesis (M.Tech.: Chiropractic) -Dept. of Chiropractic, Durban Institute of Technology, 2002 / The purpose of this randomized controlled clinical trial was to investigate the relative effectiveness of proprioceptive neuromuscular facilitation (PNF) versus ultrasound therapy for the treatment of Temporomandibular joint (TMJ) dysfunction caused by masticatory myofascial trigger points, in terms of subjective and objective clinical findings.

A dissertation presented to the Faculty of Health Sciences at the Durban University of Technology in partial compliance with the requirements for the Master’s Degree in Technology: Chiropractic, 2009 / Introduction: The aetiology of Temporomandibular Joint Dysfunction (TMJD) is not fully understood and the treatment of TMJD is controversial. Most treatment plans are based on postulated aetiology. Treatment plans currently range from pharmacological to surgical and occasionally physical therapy is also used for any myofascial component. Myofacial Trigger Points (MFTP’s) in the head and neck region have similar pain referral patterns as TMJD and there is overlap in aetiology and epidemiology. If correlation can be proved to exist between the severities of TMJD and MFTP’s then the treatment of MFTP’s can potentially decrease the severity of TMJD and then the more radical treatments can be avoided. Objectives: To determine whether TMJD was present and establish severity. To locate any MFTP’s in the Sternocleidomastiod (SCM), Temporalis, Masseter, Posterior Cervical (PC), Lateral and Medial Pterygoid muscles and determine their severity. Methods: A random sample of 25 participants were evaluated. A p value <0.05 was considered as statistically significant. Quantitative variables were summarized using median, inter-quartile range and range due to skewness of distribution, while categorical variables were described using frequency distributions and bar charts. Spearman’s nonparametric correlation analysis, and curve estimation were used to determine the existence of a relationship between TMJ severity and MFTP severity. A scatterplot was used to graphically assess the relationship. Conclusion: The results suggested that the participants were actually chronic neck pain suffers that developed TMJD over the long term as a result of chronic neck pain changing the kinematic biomechanics or as a result of a completely different and independent event as suggested by Foreman and Croft (1995).