Durante el periodo 1988 - 1991 realizamos una revisión de 300 fracturas de la extremidad distaldel radio tratadas con yeso o combinando el vendaje enyesado con agujas de Kirschnerintrafocales tipo Kapandji. El análisis de los resultados de la documentación clínica de los casos,nos permitió confeccionar un protocolo de tratamiento para estas fracturas, con el fin de podermejorar los resultados del tratamiento ortopédico, que en las fracturas 23-C solo conseguía un20% de buenos resultados.En 1990, por iniciativa de Dr. Rafael Orozco, y bajo la supervisión del Prof. Maurice E. Müllerreclasificamos 54.280 fracturas de los huesos largos tratadas con osteosíntesis, recogidasinformaticamente en el Centro de Documentación de la AO-Internacional (Grupo Internacionalpara el Estudio de la Osteosíntesis), en Berna y Davos (Suiza). El estudio se realizó siguiendo laClasificación de las fracturas de los huesos largos, publicada en 1990 por el Prof. M.E.Müller Müller 90.El motivo que nos animó a realizar este estudio fue que, a nuestra casuística, pudimos añadir unamuestra significativamente importante como la del Centro de documentación de la AO-Internacional, de donde se seleccionaron los casos de fracturas articulares completas distales deradio (tipo 23-C de la Clasificación de M.E. Müller), tratadas con Fijador Externo o con Ostesíntesis.La incidencia encontrada para estas fracturas distales de cúbito y radio (segmento 23-) fue de un5'67 % (3.094 fras.) del total de fracturas documentadas tratadas con osteosíntesis. En nuestroestudio sólo utilizaremos las fracturas 23-C (articulares completas) que son el 42'4 % (1.315 fras.)del segmento 23- tratadas quirúrgicamente. Dentro de este último grupo veremos las tratadas confijador externo o con osteosíntesis-placa.El valor de la muestra estriba en el tamaño de la misma, además de estar clasificada y tratada conunos criterios homogéneos de escuela que permiten su comparación.El interés del estudio radica en la significación de la muestra, por su tamaño, el intervalo de edadde la población implicada, la frecuencia de aparición, el tiempo de incapacidad laboral que supone,las secuelas que comporta y el coste socioeconómico que todo ello representa.

Missense, nonsense, and frameshift mutations in the human anion exchanger 1 (AE1) have been associated with inherited distal renal tubular acidosis and hereditary spherocytosis. These two disorders are almost always mutually exclusive. However, we have recently found an unusual exception, i.e, a patient with complete distal renal tubular acidosis and severe hereditary spherocytosis. DNA sequencing revealed a novel mutation AE1 E522K (Band 3 Kaohsiung) combined with AE1 G701D mutation in this patient. We hypothesize these AE1 mutations cause these two disorders because of trafficking defect. To elucidate this hypothesis, we analyzed protein trafficking and subcellular location of AE1 and these mutants transfected into MDCK cells. Our results showed that they formed homodimers or heterodimers with each other. Homodimers of the wild-type and E522K mutant were localized at the plasma membrane, whereas the G701D mutant largely remained in the cytoplasm. On the other hand, heterodimers of either E522K or G701D and the wild-type AE1 were located in the plasma membrane, whereas E522K/G701D heterodimers remained in the cytoplasm. As for erythroid isoform of anion exchanger 1, analysis of protein trafficking and subcellular localization of the wild-type erythroid isoform of human anion exchanger 1 and these mutants transfected into k562 cells also showed that they can form homodimers or heterodimers with each other. Erythroid AE1 E522K/G701D cell-surface expression was significantly lower compared with WT homodimer expression. This result coincided with that erythroid AE1 of the patient¡¦s red cell membrane can be detected 28% that of normal control in immunoblotting. Our study shows that the compound E522K/G701D mutation of human anion exchanger 1 causes trafficking defects in kidney and red blood cell lines, and these may explain the complete distal renal tubular acidosis and hereditary spherocytosis of the patient.

Purpose: To evaluate the course of recovery in fall-risk and functional status over the first year following a distal radius fracture (DRF), and evaluate differences in fall and fracture risk factors in women over the age of 50 years with a DRF compared to their non-fractured peers. Methods: Two cohorts of participants volunteered in two sub-studies of the thesis. The first was seventy-eight women recruited from a DRF Clinic within the first week after their fracture, and followed up in concert with standard clinic appointments at week three, nine, 12, 26, and 52 post-fracture. The second cohort consisted of women aged 50 years or older, with and without a recent distal radius fracture, being at least 6 months post-DRF, but no more than 2 years post-fracture. Seventy-seven women age 50-78 with (Fx, n = 32) and without (NFx = 45) a history of DRF were assessed on two occasions within 4 weeks apart using a battery of fall and fracture risk tools, including balance, mobility, gait speed, fracture risk assessment, as well as bone quality assessment using peripheral quantitative computer tomography (pQCT) and dual x-ray absorptiometry (DXA). Results: Fall-risk status (strength, balance, mobility) gradually improved over the first year post-fracture, with balance confidence remaining high even immediately post-fracture. In the second study, women with a recent DRF, compared to women without, demonstrated higher fall and fracture risk. Women with a recent DRF had lower bone and muscle strength in both the upper and lower extremities compared to the non-fractured controls, with no differences in DXA derived aBMD at the femoral neck or spine. Significance of findings: The results of these studies will help clinicians understand the normal course of functional recovery post-fracture, and assist in determining appropriate fall risk assessment and interventions for post-menopausal women at risk of fragility fracture. Results demonstrate the importance of studying women at risk of DRF as an important first indicator of bone fragility and risk of future fracture. These findings also strengthen the notion that DXA alone may not be the best predictor for fracture risk.

The Strain Index (SI) has repeatedly shown high levels of validity for differentiating between safe and hazardous tasks for the distal upper extremity (DUE). One limitation of the SI is the lack of reliability data. This study was designed to evaluate the test-retest repeatability of the SI. Fifteen raters, divided into five teams of three, were asked to use the SI to analyze 73 video AVI files of different job tasks; initially as individuals and then as teams. Several months later, raters were asked to repeat individual and team job task assessments. Raters were instructed to analyze tasks using five of six SI task variables, while the sixth was held constant. For three of these task variables, additional data was collected such as peak force and duration of job cycle. Test-retest repeatability was measured using Pearson's R, Spearman's rho, and tetrachoric correlation according to the nature of the variable. Spearman's rho values for individual and team task variable ratings ranged from 0.68 to 0.96 (0.88 average). Pearson's R for task variable data ranged from 0.76 to 0.99 for both teams and individuals with an average of 0.91. The Strain Index's rho values for individuals and teams were 0.70 and 0.84, respectively. For hazard classification, the tetrachoric correlation for individuals was 0.81 and 0.88 for teams. Results of this study support the conclusion that the Strain Index is repeatable when used by teams as well as individuals.

The Distal-less (Dll) gene has an ancient evolutionary origin. Chordates have retained duplicated Dll genes; vertebrates have six distinct paralogues (Dlx1 through Dlx6 in mammals) arranged in three cis-linked pairs that are co-expressed. Dlx genes are expressed in a conserved nested pattern that defines a proximal-distal axis in the pharyngeal arch tissue of vertebrates. Dlx5-/- and Dlx6-/- mouse neonates have similar phenotypic variations in the lower jaw and inner ear bones, with the Dlx6-/- phenotype being a less perturbed version of the Dlx5-/- phenotype. Conversely, Dlx5/6-/- double mutants have a homeotic transformation of the lower jaw into a second set of maxillary structures. The combination of expression patterns and null phenotypes has led to the proposal of a “Dlx code” that patterns the craniofacial tissue. However, the nature of this code, whether individual Dlx transcription factors supply unique functions, or whether they make a quantitative contribution to a more generic and shared Dlx function, is not well understood. One prediction of a quantitative model for Dlx function in the pharyngeal arches is the functional equivalency of the proteins encoded by divergent cis-linked Dlx paralogues. To address this aspect of the model, three core functions of Dlx5 and Dlx6 were compared quantitatively: suppression of cell growth, transcription activity and DNA binding affinity. In most respects both proteins behaved very similarly.

In vitro gut models provide several advantages over in vivo models for the study of the human gut microbiota. However, because communities developed in these models are simplified simulations of the in vivo environment it is necessary to characterize the reproducibility, repeatability and stability of cultured communities. We also need to broadly define the differences between in vitro consortia and the communities from which they are derived. In this study we characterized and validated a twin-vessel (independent, identical) single-stage chemostat model of the human distal gut. Samples were analyzed using a molecular fingerprinting technique (Denaturing Gradient Gel Electrophoresis) to compare and monitor changes in the overall structure of the communities while a phylogenetic microarray (Human Intestinal Tract Chip) was used to obtain phylogenetic information. We found that twin-vessels inoculated with feces developed and maintained diverse communities that reached stable compositions by at most 36 days post-inoculation. Communities were enriched in Bacteroidetes but not Clostridium cluster XIVa, Bacilli or other Firmicutes relative to the fecal inocula. Vessels were very reproducible when inoculated with identical fecal inocula, less similar when inoculated with consecutive fecal donations from the same donor, and maintained donor-specific identities when inoculated with feces from different donors. Norepinephrine exposure (undefined perturbation) did not appear to have a substantial effect on the structure of chemostat communities, while clindamycin treatment (defined perturbation) caused large changes in the structure of chemostat communities. Packed-column biofilm reactors incorporated a simulated mucosal environment into our chemostat system, allowing us to simultaneously culture biologically relevant planktonic and biofilm communities that were complex, reproducible, and distinct. Defined communities were comparable to fecal communities at the phylum/class-level but established stable compositions more rapidly. While it was difficult to assess the persistence of synthetic stool in a healthy fecal chemostat community (+/- antibiotic perturbation), mixing communities from two donors resulted in a mixed community that more closely resembled one donor over the other. Although future experimentation is required, the results presented here show our twin-vessel single-stage chemostat model represents a valid simulation of the human distal gut environment and can support complex, representative microbial communities ideal for experimental manipulation. / Canadian Institutes of Health Research; Ontario Ministry of Agriculture, Food and Rural Affairs; Ontario Ministry of Research and Innovation; Canada Foundation for Innovation; Ontario Ministry of Training, Colleges and Universities

Rewarming mildly hypothermic subjects with distal extremity rewarming has been associated with significantly greater rewarming rate compared to shivering-only as it increases heat flow to the core by opening up of arteriovenous anastomoses in the extremities. This study compared distal extremity rewarming with Fluidotherapy® or warm water, or shivering-only. Seven healthy individuals were cooled in 8°C water to either a core temperature of 35°C or a maximum of one hour. The subjects were then rewarmed with one of the three rewarming methods (distal extremity rewarming with 44°C water or 46°C Fluidotherapy® or shivering-only) on three different occasions. There was no significant difference in the afterdrop length and duration between the three conditions. Fluidotherapy® provided rewarming rates similar to the shivering-only condition. Warm water rewarming provided higher heat donation to distal extremities and lead to a threefold higher rewarming rate compared to the other two treatments.

Rewarming mildly hypothermic subjects with distal extremity rewarming has been associated with significantly greater rewarming rate compared to shivering-only as it increases heat flow to the core by opening up of arteriovenous anastomoses in the extremities. This study compared distal extremity rewarming with Fluidotherapy® or warm water, or shivering-only. Seven healthy individuals were cooled in 8°C water to either a core temperature of 35°C or a maximum of one hour. The subjects were then rewarmed with one of the three rewarming methods (distal extremity rewarming with 44°C water or 46°C Fluidotherapy® or shivering-only) on three different occasions. There was no significant difference in the afterdrop length and duration between the three conditions. Fluidotherapy® provided rewarming rates similar to the shivering-only condition. Warm water rewarming provided higher heat donation to distal extremities and lead to a threefold higher rewarming rate compared to the other two treatments.

La tesi doctoral engloba l'estudi de les adaptacions funcionals i estructurals que es produeixen en el còlon distal deguts als canvis en la ingesta de sodi. En concret s'ha estudiat el paper de tres hormones, l'angiotensina II, l'aldosterona i la vasopressina, en el transport de Na+, en la permeabilitat de l'epiteli i en el desenvolupament miofibroblàstic de la zona pericriptal. Mitjançant un model animal d'activació del RAAS en rata, s'han reproduït les adaptacions funcionals i estructurals en la mucosa del còlon distal en l'adaptació d'una dieta amb alt contingut en sodi (HS) a una dieta amb baix contingut en sodi (LS). Després de tan sols 3 dies de dieta LS augmenta el transport electrogènic de sodi i disminueix la permeabilitat del teixit, fet que es confirma per un augment en la densitat de les unions estretes, concretament de l'expressió de claudina 4, i per un augment en la resistència transepitelial. S'ha confirmat que en tan sols tres dies de dieta LS, la capa de miofibroblasts presents en la zona pericriptal prolifera, ja que augmenta l'expressió d'alfa-actina de múscul llis i la síntesi de col·lagen IV, augmenta l'expressió de les unions adherents que uneixen aquests miofibroblasts, concretament d'E- i OB-caderina, i es produeix acumulació de sodi en aquesta zona pericriptal. El tractament amb captopril, inhibidor de l'ECA, losartan, inhibidor dels ATr1, o espironolactona, antagonista del receptor mineralcorticoide, reverteix aquests efectes, confirmant la implicació de l'angiotensina II i l'aldosterona. Per determinar el paper concret de l'angiotensina II i de l'aldosterona en aquests efectes s'ha posat a punt un model animal d'activació del RAAS minimitzant la síntesi d'aldosterona mitjançant una operació d'adrenalectomia i controlant la concentració plasmàtica d'ambdues hormones mitjançant la seva infusió exògena. L'aldosterona, sense la presència d'angiotensina II, aconsegueix reproduir els efectes de la dieta LS augmentant el transport electrogènic de sodi, disminuint la permeabilitat del teixit, incrementant la resistència transepitelial, afavorint el creixement miofibroblàstic i augmentant l'acumulació de sodi a la zona pericriptal. L'angiotensina II, en canvi, per si sola no reprodueix aquests efectes. Els resultats obtinguts estan recollits en dues publicacions (Moretó et al., 2005; Cristià et al., 2005). També s'han estudiat els efectes del grau de deshidratació sobre les funcions del còlon distal, comprovant la implicació directa de la vasopressina i determinant els receptor implicats. Tant la deshidratació com concentracions elevades de vasopressina donen lloc a una disminució de la permeabilitat del teixit, un augment en l'acumulació de sodi a la zona pericriptal i un augment del creixement miofibroblàstic. Ambdós tipus de receptors, V1 i V2, hi estan implicats. Aquests resultats, tot i ser similars a les accions de l'aldosterona, no han demostrat un sinergisme entre ambdues hormones. A més, s'ha confirmat l'expressió d'aquaporina-2 (AQP-2) en la mucosa del còlon distal i l'augment de la seva expressió tant en estats de deshidratació com d'administració de vasopressina. L'expressió d'AQP-2 està mitjançada pel receptor V2, ja que tan sols el tractament amb Tolvaptan, un antagonista específic d'aquests receptors, l'inhibeix. Aquest estudi destaca l'aldosterona com l'hormona clau de les adaptacions del còlon distal al disminuir la ingesta de sodi de la dieta, descartant un paper directe de l'angiotensina II en aquests efectes. En condicions de deshidratació, la vasopressina també disminueix la permeabilitat de l'epiteli i indueix el desenvolupament de la beina pericriptal, a més de regular el moviment d'aigua a través d'aquaporines mitjançant els seus receptors V2 al còlon distal de rata. / Fluid and electrolyte absorption by colonic crypts depends on the transport properties of crypt cellular and paracellular routes and of the pericryptal sheath. During the transition from a high-Na+ (HS) to a low-Na+ (LS) diet there are changes in the colonic crypt wall and pericryptal sheath. The effect of angiotensin II, aldosterone and vasopressin in these changes was studied. The extracellular Na+ concentration in isolated rat distal colonic mucosa was determined by confocal microscopy using a low-affinity Na+-sensitive fluorescent dye (Sodium red, and Na+-insensitive BODIPY) bound to polystyrene beads. Crypt permeability to FITC-labelled dextran was monitored by its rate of escape from the crypt lumen into the pericryptal space. Mucosal ion permeability was estimated by transepithelial electrical resistance (TER) and amiloride-sensitive short-circuit current. Different epithelial, myofibroblasts and extracellular matrix proteins and membrane receptors were determined by immunolocalization. After only 3 days of a LS diet all colonic changes were reproduced, a decrease in crypt wall permeability, an increase in electrogenic sodium transport and a growth in the pericryptal space, that produced an increase in Na+ accumulation in the pericryptal space. The treatment with captopril, losartan and spironolactone reversed all these effects, showing the implication of angiotensin II and aldosterone. High plasma aldosterone concentrations, independently of the diet or angiotensin II, decreased crypt wall dextran permeability, increased TER, increased Na+ accumulation in the pericryptal sheath and ENaC expression, increased extracellular matrix, membrane receptors and myofibroblast proteins. Angiotensin II did not reproduced LS diet effects. High vasopressin plasma concentration raised alpha-SMA expression in the pericryptal sheath, increased the pericryptal Na+ accumulation in this space and caused a reduction of crypt wall permeability. All these effects were reversed by selective blocking of V1 and V2 receptors. Dehydration and vasopressin infusion increased AQP-2 expression in distal colonic mucosa, an effect mediated by the V2 receptor, as only the specific V2 receptor antagonist inhibited this effect. In conclusion, these findings show that aldosterone alone is responsible for the adaptative changes in the colonic crypts of distal colon due to the sodium content and that vasopressin has similar effects as aldosterone in permeability and growth development.

>Magister Scientiae - MSc / Different pathology associated with impacted wisdom teeth in the oral cavity showed that it is prevalent and may lead to varied dental complications. This study adopted a descriptive cross-sectional retrospective analytical design in order to examine hard tissue features associated with the presence of impacted third molars in a random sample of 2998 digital panoramic radiographs (DPRs) of patients' records in Tygerberg Oral Health Centre, Faculty of Dentistry, University of Western Cape. The specific objectives of the study were to categorize the type of impactions in the DPRs of patients and to determine the prevalence of distal cervical caries (DCC) in second molars, any radiolucent (RL) /radiopaque (RO) lesions or external root resorption (ERR) complications associated with impacted wisdom teeth. Results of the pantomographs and clinical records of patients indicated that the most prevalent type of impaction (TOI) is Mesioangular (MA) Impaction (65%) followed by Horizontal (H) Impaction (17%), Vertical (V) Impaction (15%), Transverse (TVS) Impaction (2 %) and Distoangular (DA) Impaction (1.2 %), respectively. The least prevalent type was Inverted (INV) Impaction with a frequency count of 0.5%. The results further indicated varied dental complications resulting from impaction, ranging from ERR with a frequency of 3% of which 66.70% was associated with MA type of impaction, followed by H with a frequency of 26.7%. The association of Gender and RL/ RO lesions was significant (p-value=0.04) while association between DCC and types of impaction was also significant (p-value =0.0017). The study concluded that the high prevalence of MA among all populations and genders over the years may be related to the anatomical normal inclination of the third molars to the mesial surface. The low prevalence of DA observed in the study sample on the other hand might be attributable to gender and demographic factors. Lastly, this study has only one radiopaque lesion and the high prevalence of RL lesions in males and in the older age group suggests that these complications take a while to develop. Future research is needed to raise more awareness and encourage patients to seek treatment of symptomatic and asymptomatic third molars before complications arise.