Salinity Effect on Horticultural Crops: Morphological, Physiological, and Biomolecular Elements of Salinity Stress Response

Among abiotic stresses, high salinity stress is the most severe environmental stress. High salinity exerts its negative impact mainly by disrupting the ionic and osmotic equilibrium of the cell. In saline soils, high levels of sodium ions lead to plant growth inhibition and even death. Salt tolerance in plants is a multifarious phenomenon involving a variety of changes at molecular, organelle, cellular, tissue as well as whole plant level. In addition, salt tolerant plants show a range of adaptations not only in morphological or structural features but also in metabolic and physiological processes that enable them to survive under extreme saline environments. The main objectives of my dissertation were understanding the main physiological and biomolecular features of plant responses to salinity in different genotypes of horticultural crops that are belonging to different families Solanaceae (tomato) and Cucurbitaceae (melon) and Brassicaceae (cabbage and radish). Several aspects of crop responses to salinity have been addressed with the final aim of combining elements of functional stress response in plants by using several ways for the assessment of plant stress perception that ranging from destructive measurements (eg. leaf area, relative growth rate, leaf area index, and total plant fresh and dry weight), to physiological determinations (eg. stomatal conductance, leaf gas exchanges, water use efficiency, and leaf water relation), to the determination of metabolite accumulation in plant tissue (eg. Proline and protein) as well as evaluation the role of enzymatic antioxidant capacity assay in scavenging reactive oxygen species that have been generated under salinized condition, and finally assessing the gene induction and up-down regulation upon salinization (eg. SOS pathway).

Evaluation of the photosynthetic efficiency of sweet sorghum under drought and cold conditions

Sweet sorghum, a C4 crop of tropical origin, is gaining momentum as a multipurpose feedstock to tackle the growing environmental, food and energy security demands. Under temperate climates sweet sorghum is considered as a potential bioethanol feedstock, however, being a relatively new crop in such areas its physiological and metabolic adaptability has to be evaluated; especially to the more frequent and severe drought spells occurring throughout the growing season and to the cold temperatures during the establishment period of the crop. The objective of this thesis was to evaluate some adaptive photosynthetic traits of sweet sorghum to drought and cold stress, both under field and controlled conditions. To meet such goal, a series of experiments were carried out. A new cold-tolerant sweet sorghum genotype was sown in rhizotrons of 1 m3 in order to evaluate its tolerance to progressive drought until plant death at young and mature stages. Young plants were able to retain high photosynthetic rate for 10 days longer than mature plants. Such response was associated to the efficient PSII down-regulation capacity mediated by light energy dissipation, closure of reaction centers (JIP-test parameters), and accumulation of glucose and sucrose. On the other hand, when sweet sorghum plants went into blooming stage, neither energy dissipation nor sugar accumulation counteracted the negative effect of drought. Two hybrids with contrastable cold tolerance, selected from an early sowing field trial were subjected to chilling temperatures under controlled growth conditions to evaluate in deep their physiological and metabolic cold adaptation mechanisms. The hybrid which poorly performed under field conditions (ICSSH31), showed earlier metabolic changes (Chl a + b, xanthophyll cycle) and greater inhibition of enzymatic activity (Rubisco and PEPcase activity) than the cold tolerant hybrid (Bulldozer). Important insights on the potential adaptability of sweet sorghum to temperate climates are given.

Evaluation eines humanisierten Mausmodells der allergischen Atemwegsentzündung

Aus der zunehmenden Prävalenz allergischer Erkrankungen vor allem in den Industrienationen ergibt sich ein erhöhter Bedarf an Grundlagenforschung im Bereich von Allergie und Asthma sowie der Entwicklung innovativer Therapiestrategien. In der vorliegenden Dissertation wurden die immundefizienten Mausstämme NOD-Scid und NOD-Scid gc als vielversprechender translationaler Schritt zwischen dem reinen Tiermodell und der Erprobung neuer Therapieansätze an Probanden in klinischen Studien beleuchtet. Im experimentellen Verlauf der Arbeit wurde ein humanisiertes Mausmodell der allergischen Atemwegsentzündung zunächst in immundefizienten NOD-Scid und darauffolgend in NOD-Scid gc Mäusen etabliert. Diese Mausstämme zeichnen sich durch das Nichtvorhandensein von B- und T-Zellen aus. Im NOD-Scid gc Stamm resultiert aus einer zusätzlichen Mutation des Gens für die gamma-Kette des IL-2 Rezeptors der Verlust von natürlichen Killerzellen (NK-Zellen), was die Immunität in diesem Stamm weiter herabsetzt und eine Humanisierung erleichtert. Die Humanisierung der Mäuse erfolgte durch die intraperitoneale Injektion von mononukleären Zellen des peripheren Blutes (PBMCs), die unter Anwendung der Ficoll-Dichtezentrifugation aus dem Blut von Probanden isoliert wurden. Für die Gewinnung der PBMCs wurden zum einen Asthma-Patienten mit einer hochgradigen Sensibilisierung gegen Birkenpollen herangezogen. Zum anderen wurden in Kontrollexperimenten PBMCs nicht-allergischer Probanden verwendet. Während sich für den NOD-Scid Stamm 80 Millionen PBMCs als angemessene Transferzahl erwiesen, reichten für die Rekonstitution des NOD-Scid gc Stammes 5 Millionen PBMCs aus. Eine Analyse der Tiere erfolgte 24 Tage nach Injektion der humanen Zellen. Der Transfer der PBMCs allergischer Asthmatiker führte besonders nach additiver Applikation des Birkenallergens sowie des humanen rekombinanten Zytokins IL-4 und darauffolgender nasaler allergener Provokation zu einer starken pulmonalen Entzündung in den Mäusen. Die nasale Allergenprovokation an den Tagen 20-22 nach PBMC-Transfer erwies sich für das Aufkommen der Inflammation als unbedingt erforderlich. Die nasale Provokation mit Phosphat-gepufferter Salzlösung (PBS) mündete in einer herabgesetzten Inflammation ohne Ausprägung einer Atemwegsüberempfindlichkeit (AHR), reduzierten Zellzahlen in der bronchoalveolären Lavage (BAL) sowie verminderten Frequenzen humaner Zellen in den Lungen von Versuchstieren, die mit atopischen PBMCs supplementiert mit Birkenallergen und IL-4 rekonstituiert wurden. Die Allergenabhängigkeit des etablierten Modells wurde anhand von Experimenten untermauert, die verdeutlichten, dass ein Transfer von PBMCs nicht-allergischer Probanden trotz Zugabe des Allergens und humanem IL-4 keine Atemwegsinflammation auslöste. Bei den humanen Zellen, die an Tag 24 nach Rekonstitution in den Mäusen detektiert werden konnten, handelte es sich hauptsächlich um T-Zellen. Innerhalb dieser CD3+ T-Zellen konnten CD4+ und CD8+ T-Zellen differenziert werden. Depletionsexperimente, in denen nach Gewinnung der PBMCs aus dem Blut der Probanden verschiedene T-Zellsubpopulationen (CD3+, CD4+, CD8+) eliminiert wurden, führten zu dem Befund, dass die allergische Atemwegsentzündung in dem System von humanen CD4+ T-Zellen abhängig war. Nach der Etablierung des humanisierten Mausmodells der allergischen Atemwegsentzündung wurde das System zur Analyse des suppressionsfördernden Potentials des HIV-1 - Hüllproteins gp120 genutzt. Die Applikation von gp120 führte zu einer Reduktion der Atemwegsinflammation. Dies äußerte sich in einer Aufhebung der AHR, verminderten Zellzahlen in der BAL sowie dem reduzierten Einstrom humaner T-Zellen in die Lungen der rekonstituierten Tiere. Weiterhin konnte gezeigt werden, dass die anti-inflammatorische Wirkung des gp120 strikt von der Anwesenheit regulatorischer T-Zellen (Tregs) innerhalb der für die Humanisierung genutzten PBMCs abhängig war. Eine Depletion der Tregs vor Transfer in die Mäuse führte zum Verlust der anti-inflammatorischen Effekte des gp120. Diese Ergebnisse sprechen für die Modulation regulatorischer T-Zellen als hoffnungsvolle Maßnahme in der Behandlung allergischer Erkrankungen. Die im Rahmen dieser Arbeit gewonnenen Erkenntnisse eröffnen innovative Ansätze zur Analyse neuer Therapiestrategien in einem Testsystem, dass die Erforschung humaner Zellinteraktionen sowie die Wirkung potentieller Arzneistoffe auf humane Zellen unter in vivo Bedingungen erlaubt.

Functional dna nanostructures for in vitro biosensing in live cells

DNA is a fascinating biomolecule that is well known for its genetic role in living systems. The emerging area of DNA nanotechnology provides an alternative view that exploits unparallel self-assembly ability of DNA molecules for material use of DNA. Although many reports exist on the results of DNA self-assembling systems, still few of them focus on the in vitro study about the function of such DNA nanostructures in live cells. Due to this, there are still a limited research about the in vitro functionality of such designs. To address an aspect of this issue, we have designed, synthesized and characterized two multifunctional fluorescencent nanobiosensors by DNA self-assembling. Each structure was designed and implemented to be introduced in live cells in order to give information on their functioning in real-time. Computational tools were used in order to design a graphic model of two new DNA motifs and also to obtain the specific sequences to all the ssDNA molecules. By thermal self-assembly techniques we have successfully synthesized the structure and corroborate their formation by the PAGE technique. In addition, we have established the conditions to characterize their structural conformation change when they perform their sensor response. The sensing behavior was also accomplished by fluorescence spectroscopy techniques; FRET evaluation and fluorescence microscopy imaging. Providing the evidence about their adequate sensing performance outside and inside the cells detected in real-time. In a preliminary evaluation we have tried to show the in vitro functionality of our structures in different cancer cell lines with the ability to perform local sensing responses. Our findings suggest that DNA sensor nanostructures could serve as a platform to exploit further therapeutic achievements in live cells.

Evaluation of 3D cell culture systems for host-pathogen interaction studies

Traditional cell culture models have limitations in extrapolating functional mechanisms that underlie strategies of microbial virulence. Indeed during the infection the pathogens adapt to different tissue-specific environmental factors. The development of in vitro models resembling human tissue physiology might allow the replacement of inaccurate or aberrant animal models. Three-dimensional (3D) cell culture systems are more reliable and more predictive models that can be used for the meaningful dissection of host–pathogen interactions. The lung and gut mucosae often represent the first site of exposure to pathogens and provide a physical barrier against their entry. Within this context, the tracheobronchial and small intestine tract were modelled by tissue engineering approach. The main work was focused on the development and the extensive characterization of a human organotypic airway model, based on a mechanically supported co-culture of normal primary cells. The regained morphological features, the retrieved environmental factors and the presence of specific epithelial subsets resembled the native tissue organization. In addition, the respiratory model enabled the modular insertion of interesting cell types, such as innate immune cells or multipotent stromal cells, showing a functional ability to release pertinent cytokines differentially. Furthermore this model responded imitating known events occurring during the infection by Non-typeable H. influenzae. Epithelial organoid models, mimicking the small intestine tract, were used for a different explorative analysis of tissue-toxicity. Further experiments led to detection of a cell population targeted by C. difficile Toxin A and suggested a role in the impairment of the epithelial homeostasis by the bacterial virulence machinery. The described cell-centered strategy can afford critical insights in the evaluation of the host defence and pathogenic mechanisms. The application of these two models may provide an informing step that more coherently defines relevant molecular interactions happening during the infection.

Evaluation zellulärer Mechanismen der allergen-spezifischen Immuntherapie in einem chronischen Modell der allergischen Atemwegsentzündung

Klinische Studien haben gezeigt, dass die allergenspezifische Immuntherapie (SIT) eine effektive Therapieoption für allergische Erkrankungen ist. Obwohl dieses Therapieverfahren seit über 100 Jahren existiert, sind die zugrunde liegenden Suppressionsmechanismen jedoch nicht vollständig verstanden. Bisher wird angenommen, dass der Behandlungserfolg der SIT auf einer Blockade durch allergenspezifische Antikörper, einer Verschiebung des Th1-Th2-Gleichgewichtes und/oder auf einer Suppression durch regulatorische T-Zellen (Tregs) basiert. Um die Effekte der SIT in einer chronischen Erkrankung in vivo untersuchen zu können, wurde in dieser Doktorarbeit ein Mausmodell für chronisches Asthma entwickelt, das die Situation im Menschen nach einer SIT nachahmt. rnDurch eine SIT war es möglich, allergeninduzierte Asthmasymptome wie Atemwegshyperreagibilität (AHR), Eosinophilie in der Lunge, IgE-Produktion und Atemwegsentzündung im Modell zu unterdrücken. Bemerkenswert ist, dass durch OVA-spezifische Immuntherapie (OVA-IT) ebenfalls eine Verringerung der strukturellen Veränderungen im Lungengewebe im chronischen Krankheitsverlauf erreicht wurde.rnDes Weiteren wurde in diesem Modell nach den Prozessen gesucht, die für die toleranzinduzierende Wirkung der SIT verantwortlich sein können. Dabei wurde im Vergleich zur Placebo-behandelten Gruppe eine erhöhte Antwort spezifischer IgG1-Antikörper, eine verstärkte Th1-Antwort, sowie eine erhöhte Frequenz von FoxP3+ Tregs und von IL-10-produzierenden T-Zellen (Tr1-Zellen) nach OVA-IT festge-stellt. Zur weiteren Untersuchung der von SIT-induzierten T-Zellantworten wurden Mausmodelle des allergischen Asthmas mit einem akuten Verlauf gewählt.rnDie Bedeutung der Th1-Zellen für die SIT wurde in T-bet-/- Mäusen untersucht, welche aufgrund des Fehlens des Transkriptionsfaktors T-bet keine stabile Th1-Antwort induzieren können. Durch SIT war es möglich, allergeninduzierte Asthmasymptome wie AHR, eosinophile Granulozyten in der Lunge, IgE-Produktion und Atemwegsentzündung in den T-bet-/- Tieren im gleichen Maße wie in den Wildtyptieren zu unterdrücken. Diese Untersuchung zeigte, dass die SIT auch ohne funktionelle Th1-Zellen die allergische Entzündung unterdrücken kann. rnDie Rolle der Tregs für die SIT wurde in DO11.10 Mäusen und DO11.10 RAG-/- Mäusen untersucht. In beiden Stämmen konnte nach SIT eine Induktion OVA-spezifischer Tregs nachgewiesen werden. In DO11.10 RAG-/- Mäusen können durch den Knockout im rag2-Gen keine natürlichen, d.h. im Thymus gereiften, Tregs entstehen. Im Blut von DO11.10 RAG-/- Mäusen war direkt nach Durchführung der OVA-IT eine FoxP3+ Treg-Population detektierbar. Demnach wird durch die OVA-IT eine de-novo-Induktion von FoxP3+ Tregs in Gang gesetzt. In Abwesenheit der natürlichen Tregs zeigte sich weiterhin, dass diese Zellen zur Produktion von IL-10 in T-Zellen und somit zum Erfolg der SIT beitragen.rnDie Rolle der FoxP3+ Tregs bei der SIT wurde in DEREG Mäusen untersucht. Eine Depletion der FoxP3+ Tregs in DEREG Mäusen während der Durchführung der OVA-IT hob die protektiven Effekte der Therapie jedoch nur teilweise auf. rnUm die Rolle des regulatorischen Zytokins IL-10 bei der SIT zu untersuchen, wurde ein blockierender Antikörper gegen den IL-10-Rezeptor (anti-IL-10R) im chronischen Modell des allergischen Asthmas mit SIT angewendet. Anti-IL-10R hob die protektive Wirkung der SIT auf die AHR, die Atemwegsentzündung und die strukturellen Veränderungen im Lungengewebe auf. Somit ist die protektive Wirkung der SIT abhängig vom IL-10-Signalweg.rnZusammenfassend stellt diese Arbeit die Bedeutung der SIT für allergische Erkrankungen heraus. SIT kann durch die positive Beeinflussung der allergiebedingten, strukturellen Veränderungen in der Lunge auch für Asthmapatienten große Vorteile bringen. Die aus Studien bekannten Mechanismen konnten im Modell bestätigt werden und wurden im weiteren Verlauf untersucht. Die Arbeit stellt im Besonderen die Bedeutung der IL-10-produzierenden und FoxP3+ Tregs für die Effektivität der SIT in den Vordergrund. Zudem ist durch die Etablierung eines neuen Mausmodells der SIT für chronisches allergisches Asthma ein Mittel zur weiteren Erforschung der zugrunde liegenden Prozesse dieser erfolgreichen Therapie geschaffen worden. rn

Tetraamine-derived bifunctional chelators for technetium-99m labelling: synthesis, bioconjugation and evaluation as targeted SPECT imaging probes for GRP-receptor-positive tumours

Owing to its optimal nuclear properties, ready availability, low cost and favourable dosimetry, (99m)Tc continues to be the ideal radioisotope for medical-imaging applications. Bifunctional chelators based on a tetraamine framework exhibit facile complexation with Tc(V)O(2) to form monocationic species with high in vivo stability and significant hydrophilicity, which leads to favourable pharmacokinetics. The synthesis of a series of 1,4,8,11-tetraazaundecane derivatives (01-06) containing different functional groups at the 6-position for the conjugation of biomolecules and subsequent labelling with (99m)Tc is described herein. The chelator 01 was used as a starting material for the facile synthesis of chelators functionalised with OH (02), N(3) (04) and O-succinyl ester (05) groups. A straightforward and easy synthesis of carboxyl-functionalised tetraamine-based chelator 06 was achieved by using inexpensive and commercially available starting materials. Conjugation of 06 to a potent bombesin-antagonist peptide and subsequent labelling with (99m)Tc afforded the radiotracer (99m)Tc-N4-BB-ANT, with radiolabelling yields of >97% at a specific activity of 37 GBq micromol(-1). An IC(50) value of (3.7+/-1.3) nM was obtained, which confirmed the high affinity of the conjugate to the gastrin-releasing-peptide receptor (GRPr). Immunofluorescence and calcium mobilisation assays confirmed the strong antagonist properties of the conjugate. In vivo pharmacokinetic studies of (99m)Tc-N4-BB-ANT showed high and specific uptake in PC3 xenografts and in other GRPr-positive organs. The tumour uptake was (22.5+/-2.6)% injected activity per gram (% IA g(-1)) at 1 h post injection (p.i.). and increased to (29.9+/-4.0)% IA g(-1) at 4 h p.i. The SPECT/computed tomography (CT) images showed high tumour uptake, clear background and negligible radioactivity in the abdomen. The promising preclinical results of (99m)Tc-N4-BB-ANT warrant its potential candidature for clinical translation.

Coronary optical frequency domain imaging (OFDI) for in vivo evaluation of stent healing: comparison with light and electron microscopy

Coronary late stent thrombosis, a rare but devastating complication, remains an important concern in particular with the increasing use of drug-eluting stents. Notably, pathological studies have indicated that the proportion of uncovered coronary stent struts represents the best morphometric predictor of late stent thrombosis. Intracoronary optical frequency domain imaging (OFDI), a novel second-generation optical coherence tomography (OCT)-derived imaging method, may allow rapid imaging for the detection of coronary stent strut coverage with a markedly higher precision when compared with intravascular ultrasound, due to a microscopic resolution (axial approximately 10-20 microm), and at a substantially increased speed of image acquisition when compared with first-generation time-domain OCT. However, a histological validation of coronary OFDI for the evaluation of stent strut coverage in vivo is urgently needed. Hence, the present study was designed to evaluate the capacity of coronary OFDI by electron (SEM) and light microscopy (LM) analysis to detect and evaluate stent strut coverage in a porcine model.

Long-term evaluation of myoblast seeded patches implanted on infarcted rat hearts

Cell transplantation presents great potential for treatment of patients with severe heart failure. However, its clinical application was revealed to be more challenging than initially expected in experimental studies. Further investigations need to be undertaken to define the optimal treatment conditions. We previously reported on the epicardial implantation of a bio-engineered construct of skeletal myoblast-seeded polyurethane and its preventive effect on progression toward heart failure. In the present study, we present a long-term evaluation of this functional outcome. Left anterior descending coronary ligation was performed in female Lewis rats. Two weeks later, animals were treated with either epicardial implantation of biograft, acellular scaffold, sham operation, or direct intramyocardial skeletal myoblast injection. Functional assessments were performed with serial echocardiographies every 3 months and end point left ventricle pressure was assessed. Hearts were then harvested for histological examinations. Myocardial infarction induced a slow and progressive reduction in fractional shortening after 3 months. Progression toward heart failure was significantly prevented for up to 6 months after injection of myoblasts and for up to 9 months following biograft implantation. Nevertheless, this effect vanished after 12 months, with immunohistological examinations revealing an absence of the transplanted myoblasts within the scaffold. We demonstrated that tissue therapy is superior to cell therapy for stabilization of heart function. However, beneficial effects are transient.

The Lower Limb Functional Index: development and clinimetric properties

Background Existing lower-limb, region-specific, patient-reported outcome measures have clinimetric limitations, including limitations in psychometric characteristics (eg, lack of internal consistency, lack of responsiveness, measurement error) and the lack of reported practical and general characteristics. A new patient-reported outcome measure, the Lower Limb Functional Index (LLFI), was developed to address these limitations. Objective The purpose of this study was to overcome recognized deficiencies in existing lower-limb, region-specific, patient-reported outcome measures through: (1) development of a new lower-extremity outcome scale (ie, the LLFI) and (2) evaluation of the clinimetric properties of the LLFI using the Lower Extremity Functional Scale (LEFS) as a criterion measure. Design This was a prospective observational study. Methods The LLFI was developed in a 3-stage process of: (1) item generation, (2) item reduction with an expert panel, and (3) pilot field testing (n=18) for reliability, responsiveness, and sample size requirements for a larger study. The main study used a convenience sample (n=127) from 10 physical therapy clinics. Participants completed the LLFI and LEFS every 2 weeks for 6 weeks and then every 4 weeks until discharge. Data were used to assess the psychometric, practical, and general characteristics of the LLFI and the LEFS. The characteristics also were evaluated for overall performance using the Measurement of Outcome Measures and Bot clinimetric assessment scales. Results The LLFI and LEFS demonstrated a single-factor structure, comparable reliability (intraclass correlation coefficient [2,1]=.97), scale width, and high criterion validity (Pearson r=.88, with 95% confidence interval [CI]). Clinimetric performance was higher for the LLFI compared with the LEFS on the Measurement of Outcome Measures scale (96% and 95%, respectively) and the Bot scale (100% and 83%, respectively). The LLFI, compared with the LEFS, had improved responsiveness (standardized response mean=1.75 and 1.64, respectively), minimal detectable change with 90% CI (6.6% and 8.1%, respectively), and internal consistency (α=.91 and .95, respectively), as well as readability with reduced user error and completion and scoring times. Limitations Limitations of the study were that only participants recruited from outpatient physical therapy clinics were included and that no specific conditions or diagnostic subgroups were investigated. Conclusion The LLFI demonstrated sound clinimetric properties. There was lower response error, efficient completion and scoring, and improved responsiveness and overall performance compared with the LEFS. The LLFI is suitable for assessment of lower-limb function.

Morphological and functional 3-Tesla magnetic resonance imaging of saphenous vein coronary artery bypass grafts

Evaluation of a novel non-invasive tool for postoperative follow-up of patients postelective saphenous vein coronary artery bypass graft (CABG) was performed. Ten patients were included. Their bypass grafts supplied the right coronary artery (7), marginal branches (1), diagonal branches (2), and the circumflex artery (n=1). Each bypass was examined intraoperatively using Doppler flow measurement. Patients were examined with a 3-Tesla magnetic resonance imaging (MRI) scanner (MAGNETOM Verio, Siemens, Erlangen, Germany) within one week postsurgery using MR-angiography with an intravasal contrast agent and velocity encoded phase-contrast flow measurements. Intraoperative Doppler flow measurements revealed regular flow patterns in all vascular territories supplied. The median intraoperative flow rate was 50 ml/min with an inter-quartile range (IQR) of 42-70 ml/min. The clinical postoperative course was uneventful. MRI showed all grafts to be patent. The median postoperative flow rate was 50 ml/min (IQR: 32-65 ml/min). MRI flow rates agreed well with intraoperative Doppler flow measurements (mean difference: -2.8±20.1 ml/min). This initial study demonstrates that 3-Tesla MRI flow measurements correlated well with Doppler thus reconfirming the graft patency postCABG. Further refinement and broader application of this technique may facilitate follow-up postCABG potentially replacing empiric clinical judgment by reliable non-invasive imaging.

Unconventional implants for distal cantilever fixed full-arch prostheses: a long-term evaluation of four cases

Excessive cantilever lengths of fixed implant-supported prostheses may have functional and biomechanical disadvantages. This study reports the clinical outcomes of unconventional implants placed for distal support of a fixed implant-supported prostheses. Seven extraoral implants with intraosseous lengths of 2.5 to 4.0 mm were placed in four patients. Distal cantilevers had a mean length of 29.8 mm (range, 18.6 to 39.3 mm). No bone loss or other adverse events were found. The prosthetic plan was maintained in all patients. Within the limits of the employed research design, this concept seems to be a successful option for fixed complete implant-supported prosthesis treatment.

Total hip arthroplasty: leg length inequality impairs functional outcomes and patient satisfaction

Background Leg length inequality (LLI) was identified as a problem of total hip arthroplasty soon after its introduction. Leg lengthening is the most common form of LLI. Possible consequences are limping, neuronal dysfunction and aseptic component loosening. LLI can result in an increased strain both on the contralateral hip joint and on the abductor muscles. We assessed the influence of leg lengthening and shortening on walking capacity, hip pain, limping and patient satisfaction at 2-year follow-up. Methods 478 cases with postoperative lengthening and 275 with shortening were identified, and matched with three controls each. Rigorous adjustment for potential differences in baseline patient characteristics was performed by propensity-score matching of covariates. The arbitrarily defined desired outcomes were a walking capacity >60 minutes, no hip pain, no limping, and excellent patient satisfaction. Differences in not achieving the desired outcomes between the groups were expressed as odds ratios. Results In the lengthened case group, the odds ratio for not being able to walk for an hour was 1.70 (95% CI 1.28-2.26) for cases compared to controls, and the odds ratio for having hip pain at follow-up was 1.13 (95% CI 0.78-1.64). The odds ratio for limping was 2.08 (95% CI 1.55-2.80). The odds ratio for not achieving excellent patient satisfaction was 1.67 (95% CI 1.23-2.28). In the shortening case group, the odds ratio for not being able to walk for an hour was 1.23 (95% CI 0.84-1.81), and the odds ratio for having hip pain at follow-up was 1.60 (95% CI 1.05-2.44). The odds ratio for limping for cases was 2.61 (95% CI 1.78-3.21). The odds ratio for not achieving excellent patient satisfaction was 2.15 (95% CI 1.44-3.21). Conclusions Walking capacity, limping and patient satisfaction were all significantly associated with leg lengthening, whereas pain alleviation was not. In contrast, hip pain, limping and patient satisfaction were all significantly associated with leg shortening, whereas walking capacity was not.

The Development, Reliability, and Validity of the OARS Multidimensional Functional Assessment Questionnaire

This report outlines the development, validity, and reliability of Part A of the OARS Multidimensional Functional Assessment Questionnaire. Part A permits assessment of individuals' functioning on each of five dimensions (social, economic, mental health, physical health and self-care capacity), the detailed information in each area being summarized on a 6-point rating scale by a rater. Content and consensual validity were ensured by the manner of construction. Information on criterion validity was obtained for all dimensions except social. The criterion used and their associated Kendall's Tau values were: an objective economic scale (.62); ratings based on personal interviews by geropsychiatrists (.60); physician's associates (.82); and physical therapists (.89). For 11 geographically dispersed raters from research and clinic settings, intraclass correlational coefficients, based on 30 subjects, ranged from .66 on physical health to .87 in self-care capacity; 74% of the ratings were in complete agreement, 24% differed by one point.

The effect of terazosin on functional bladder outlet obstruction in women: a pilot study

PURPOSE: We assessed the effect of terazosin (Hytrin(R)) on functional bladder outlet obstruction in women. MATERIALS AND METHODS: Functional bladder outlet obstruction was defined as a maximum flow rate of less than 12 ml per second combined with a detrusor pressure at maximum flow rate of more than 20 cm H2O in pressure flow studies in the absence of neurological disorders or mechanical causes. In a prospective pilot study 15 women with functional bladder outlet obstruction were treated with terazosin. Terazosin was initiated at 1 mg daily and gradually increased to the maintenance dose of 5 mg daily during 2 weeks. Symptoms and urodynamic parameters were assessed before and 3 to 4 weeks after the initiation of alpha-blocker therapy. RESULTS: While on terazosin, voiding symptoms subjectively improved greater than 50% in 10 of the 15 women (p = 0.002). Median maximum urethral closure pressure at rest decreased significantly from 98 to 70 cm H2O (p = 0.001), median maximum detrusor pressure decreased from 45 to 35 cm H2O (p = 0.008), median detrusor pressure at maximum flow decreased from 34 to 27 ml per second and median post-void residual urine decreased from 120 to 40 ml (p = 0.006 and 0.002, respectively). There was a significant increase in the median maximum flow rate from 9 to 20 ml per second and in median voided volume from 300 to 340 ml (p = 0.0005 and 0.021, respectively). Storage symptoms, functional urethral length and maximum cystometric capacity did not change significantly with alpha-blocker therapy (p > 0.05). Overall terazosin resulted in a significant improvement in symptoms and urodynamic parameters in 10 of the 15 women (67%). CONCLUSIONS: Terazosin had a significant symptomatic and urodynamic effect in two-thirds of our patients. These results suggest that terazosin may be an effective treatment option in women with voiding dysfunction due to functional bladder outlet obstruction.