Optimal designs for evaluating a series of treatments

Several articles in this journal have studied optimal designs for testing a series of treatments to identify promising ones for further study. These designs formulate testing as an ongoing process until a promising treatment is identified. This formulation is considered to be more realistic but substantially increases the computational complexity. In this article, we show that these new designs, which control the error rates for a series of treatments, can be reformulated as conventional designs that control the error rates for each individual treatment. This reformulation leads to a more meaningful interpretation of the error rates and hence easier specification of the error rates in practice. The reformulation also allows us to use conventional designs from published tables or standard computer programs to design trials for a series of treatments. We illustrate these using a study in soft tissue sarcoma.

ADAMs, Osteoclastogenesis and Bone Destruction in the Loosening of the Totally Replaced Hip

Total hip replacement is the golden standard treatment for severe osteoarthritis refractory for conservative treatment. Aseptic loosening and osteolysis are the major long-term complications after total hip replacement. Foreign body giant cells and osteoclasts are locally formed around aseptically loosening implants from precursor cells by cell fusion. When the foreign body response is fully developed, it mediates inflammatory and destructive host responses, such as collagen degradation. In the present study, it was hypothesized that the wear debris and foreign body inflammation are the forces driving local osteoclast formation, peri-implant bone resorption and enhanced tissue remodeling. Therefore the object was to characterize the eventual expression and the role of fusion molecules, ADAMs (an abbreviation for A Disintegrin And Metalloproteinase, ADAM9 and ADAM12) in the fusion of progenitor cells into multinuclear giant cells. For generation of such cells, activated macrophages trying to respond to foreign debris play an important role. Matured osteoclasts together with activated macrophages mediate bone destruction by secreting protons and proteinases, including matrix metalloproteinases (MMPs) and cathepsin K. Thus this study also assessed collagen degradation and its relationship to some of the key collagenolytic proteinases in the aggressive synovial membrane-like interface tissue around aseptically loosened hip replacement implants. ADAMs were found in the interface tissues of revision total hip replacement patients. Increased expression of ADAMs at both transcriptional and translational levels was found in synovial membrane-like interface tissue of revision total hip replacement (THR) samples compared with that in primary THR samples. These studies also demonstrate that multinucleate cell formation from monocytes by stimulation with macrophage-colony stimiulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL) is characterized by time dependent changes of the proportion of ADAMs positive cells. This was observed both in the interface membrane in patients and in two different in vitro models. In addition to an already established MCS-F and RANKL driven model, a new virally (parainfluenza 2) driven model (of human salivary adenocarcinoma (HSY) cells or green monkey kidney (GMK) cells) was developed to study various fusion molecules and their role in cell fusion in general. In interface membranes, collagen was highly degraded and collagen degradation significantly correlated with the number of local cells containing collagenolytic enzymes, particularly cathepsin K. As a conclusion, fusion molecules ADAM9 and ADAM12 seem to be dynamically involved in cell-cell fusion processes and multinucleate cell formation. The highly significant correlation between collagen degradation and collagenolytic enzymes, particularly cathepsin K, indicates that the local acidity of the interface membrane in the pathologic bone and soft tissue destruction. This study provides profound knowledge about cell fusion and mechanism responsible for aseptic loosening as well as increases knowledge helpful for prevention and treatment.

Cervical headgear in Class II division 1 correction in children : Academic Dissertation

Class II division 1 malocclusion occurs in 3.5 to 13 percent of 7 12 year-old children. It is the most common reason for orthodontic treatment in Finland. Correction is most commonly performed using headgear treatment. The aim of this study was to investigate the effects of cervical headgear treatment on dentition, facial skeletal and soft tissue growth, and upper airway structure, in children. 65 schoolchildren, 36 boys and 29 girls were studied. At the onset of treatment a mean age was 9.3 (range 6.6 12.4) years. All the children were consequently referred to an orthodontist because of Class II division 1 malocclusion. The included children had protrusive maxilla and an overjet of more than 2mm (3 to 11 mm). The children were treated with a Kloehn-type cervical headgear as the only appliance until Class I first molar relationships were achieved. The essential features of the headgear were cervical strong pulling forces, a long upward bent outer bow, and an expanded inner bow. Dental casts and lateral and posteroanterior cephalograms were taken before and after the treatment. The results were compared to a historical, cross-sectional Finnish cohort or to historical, age- and sex-matched normal Class I controls. The Class I first molar relationships were achieved in all the treated children. The mean treatment time was 1.7 (range 0.3-3.1) years. Phase 2 treatments were needed in 52% of the children, most often because of excess overjet or overbite. The treatment decreased maxillary protrusion by inhibiting alveolar forward growth, while the rest of the maxilla and mandible followed normal growth. The palate rotated anteriorly downward. The expansion of the inner bow of the headgear induced widening of the maxilla, nasal cavity, and the upper and lower dental arches. Class II malocclusion was associated with narrower oro- and hypopharyngeal space than in the Class I normal controls. The treatment increased the retropalatal airway space, while the rest of the airway remained unaffected. The facial profile improved esthetically, while the facial convexity decreased. Facial soft tissues masked the facial skeletal convexity, and the soft tissue changes were smaller than skeletal changes. In conclusion, the headgear treatment with the expanded inner bow may be used as an easy and simple method for Class II correction in growing children.

Efficient implementations of a pseudodynamical stochastic filtering strategy for static elastography

A computationally efficient pseudodynamical filtering setup is established for elasticity imaging (i.e., reconstruction of shear modulus distribution) in soft-tissue organs given statically recorded and partially measured displacement data. Unlike a regularized quasi-Newton method (QNM) that needs inversion of ill-conditioned matrices, the authors explore pseudodynamic extended and ensemble Kalman filters (PD-EKF and PD-EnKF) that use a parsimonious representation of states and bypass explicit regularization by recursion over pseudotime. Numerical experiments with QNM and the two filters suggest that the PD-EnKF is the most robust performer as it exhibits no sensitivity to process noise covariance and yields good reconstruction even with small ensemble sizes.

Array Comparative Genomic Hybridization in Sarcomas

Over the past years, much research on sarcomas based on low-resolution cytogenetic and molecular cytogenetic methods has been published, leading to the identification of genetic abnormalities partially underlying the tumourigenesis. Continued progress in the identification of genetic events such as copy number aberrations relies upon adapting the rapidly evolving high-resolution microarray technology, which will eventually provide novel insights into sarcoma biology, and targets for both diagnostics and drug development. The aim of this Thesis was to characterize DNA copy number changes that are involved in the pathogenesis of soft tissue leiomyosarcoma (LMS), dermatofibrosarcoma protuberans (DFSP), osteosarcoma (OS), malignant fibrous histiocytoma (MFH), and uterine leiomyosarcoma (ULMS) by applying fine resolution array comparative genomic hybridization (aCGH) technology. Both low- and high-grade LMS tumours showed distinct copy number patterns, in addition to sharing two minimal common regions of gains and losses. Small aberrations were detected by aCGH, which were beyond the resolution of chromosomal comparative genomic hybridization (cCGH). DFSP tumours analysed by aCGH showed gains in 17q, 22q, and 21 additional gained regions, but only one region (22q) with copy number loss. Recurrent amplicons identified in OS by aCGH were 12q11-q15, 8q, 6p12-p21, and 17p. Amplicons 12q and 17p were further characterized in detail. The amplicon at 17p was characterized by aCGH in low- and high-grade LMS, OS, and MFH. In all but one case this amplicon, with minimal common regions of gains at 17p11-p12, started with the distal loss of 17p13-pter. OS and high-grade LMS were grouped together as they showed a complex pattern of copy number gains and amplifications at 17p, whereas MFH and low-grade LMS showed a continuous pattern of copy number gains and amplification at 17p. In addition to the commonly gained and lost regions identified in ULMS by aCGH, various biological processes affected by these copy number changes were also indicated by pathway analysis. The three novel findings obtained in this work were: characterization of amplicon 17p in low- and high-grade LMS and MFH, profiles of DNA copy number changes in LMS, and detection of various pathways affected by copy number changes in ULMS. These studies have not been undertaken previously by aCGH technology, thus this Thesis adds new information regarding DNA copy number changes in sarcomas. In conclusion, the aCGH technique used in this Thesis has provided new insights into the genetics of sarcomas by detecting the precise regions affected by copy number changes and some potential candidate target genes within those regions, which had not been uncovered by previously applied low resolution techniques.

The Role Of Fumarase (FH) In Tumorigenesis

In this study, a predisposing gene for a recently characterized cancer syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC), was identified and the role of the gene was investigated in other familial cancers and in nonsyndromic tumorigenesis. HLRCC is a dominantly inherited disorder predisposing predominantly to uterine and skin leiomyomas, and also to renal cell cancer and uterine leiomyosarcoma. The disease gene was recently localized in Finnish families to 1q42-q43 by a genome-wide linkage search. Independently in the UK, a clinically similar condition, multiple cutaneous and uterine leiomyomata (MCUL), was linked to the same chromosomal region, strongly suggesting that HLRCC and MCUL are actually a single syndrome. Linkage results were confirmed by detecting loss of heterozygosity (LOH) at the disease locus in most of the patients' tumors, suggesting that this predisposing gene acts as a tumor suppressor. Through detailed investigation by genotyping of microsatellite markers and haplotype construction in Finnish and UK HLRCC/MCUL families we were able to narrow the disease locus down to 1.6 Mb. Extensive mutation screening of known and predicted transcripts in the target region resulted in identification of the HLRCC predisposing gene, fumarase (fumarate hydratase, FH). FH is a key enzyme in energy metabolism, catalyzing fumarate to malate in the tricarboxylic acid cycle (TCAC) in mitochondria. Germline alterations in FH segregating with the disease were detected in 25 of 42 HLRCC/MCUL families including whole-gene deletions, truncating small deletions/insertions and nonsense mutations, as well as substitutions or deletions of highly conserved amino acids. Biallelic inactivation was detected in almost all studied tumors of HLRCC patients. Furthermore, FH enzyme activity was reduced in the patients' normal tissues and was completely or virtually absent from tumors. Based on these findings, we extensively demonstrated that mutations in FH underlie the HLRCC/MCUL syndrome. In our studies of other familial cancers, evidence for involvement of FH defects was not found in familial prostate and breast cancers. To investigate the role of FH in sporadic tumorigenesis, we analyzed 652 lesions, including a series of 353 nonsyndromic counterparts of tumor types associated with HLRCC. Mutations in nonsyndromic tumors were rare and appeared to be limited to tumor types observed in the hereditary form of the disease. Biallelic inactivation of FH was detected in a uterine leiomyosarcoma, a cutaneous leiomyoma, a soft-tissue sarcoma, and in two uterine leiomyomas. In the uterine leiomyosarcoma and the cutaneous lesion FH mutations originated from the germline whereas the soft-tissue sarcoma harbored purely somatic changes. In uterine leiomyomas somatic mutations were detected in the two out of five tumors with LOH at the FH locus. Our findings demonstrate that FH inactivation is also involved in nonhereditary tumor development, and further support the hypothesis that FH acts as a tumor suppressor. The role of FH in predisposition to malignancies, renal cell carcinoma and leiomyosarcoma is important in the diagnosis and prevention of cancer among HLRCC patients. This study is of general clinical interest, because prior to our findings, little was known about the molecular genetics of uterine leiomyomas, the most common tumors of women.

Microarrays in Molecular Profiling of Ewing Sarcoma Family of Tumors and CDKN2A Aberrations

Background: The Ewing sarcoma family of tumors (ESFT) are rare but highly malignant neoplasms that occur mainly in bone or but also in soft tissue. ESFT affects patients typically in their second decade of life, whereby children and adolescents bear the heaviest incidence burden. Despite recent advances in the clinical management of ESFT patients, their prognosis and survival are still disappointingly poor, especially in cases with metastasis. No targeted therapy for ESFT patients is currently available. Moreover, based merely on current clinical and biological characteristics, accurate classification of ESFT patients often fails at the time of diagnosis. Therefore, there is a constant need for novel molecular biomarkers to be applied in tandem with conventional parameters to further intensify ESFT risk-stratification and treatment selection, and ultimately to develop novel targeted therapies. In this context, a greater understanding of the genetics and immune characteristics of ESFT is needed. Aims: This study sought to open novel insights into gene copy number changes and gene expression in ESFT and, further, to enlighten the role of inflammation in ESFT. For this purpose, microarrays were used to provide gene-level information on a genomewide scale. In addition, this study focused on screening of 9p21.3 deletion sizes and frequencies in ESFT and, in another pediatric cancer, acute lymphocytic leukemia (ALL), in order to define more exact criteria for highrisk patient selection and to provide data for developing a more reliable diagnostic method to detect CDKN2A deletions. Results: In study I, 20 novel ESFT-associated suppressor genes and oncogenes were pinpointed using combined array CGH and expression analysis. In addition, interesting chromosomal rearrangements were identified: (1) Duplication of derivative chromosome der(22)(11;22) was detected in three ESFT patients. This duplication included the EWSR1-FLI1 fusion gene leading to increase in its copy number; (2) Cryptic amplifications on chromosomes 20 and 22 were detected, suggesting a novel translocation between chromosomes 20 and 22, which most probably produces a fusion between EWSR1 and NFATC2. In study II, bioinformatic analysis of ESFT expression profiles showed that inflammatory gene activation is detectable in ESFT patient samples and that the activation is characterized by macrophage gene expression. Most interestingly, ESFT patient samples were shown to express certain inflammatory genes that were prognostically significant. High local expression of C5 and JAK1 at the tumor site was shown to associate with favorable clinical outcome, whereas high local expression of IL8 was shown to be detrimental. Studies III and IV showed that the smallest overlapping region of deletion in 9p21.3 includes CDKN2A in all cases and that the length of this region is 12.2 kb in both Ewing sarcoma and ALL. Furthermore, our results showed that the most widely used commercial CDKN2A FISH probe creates false negative results in the narrowest microdeletion cases (<190 kb). Therefore, more accurate methods should be developed for the detection of deletions in the CDKN2A locus. Conclusions: This study provides novel insights into the genetic changes involved in the biology of ESFT, in the interaction between ESFT cells and immune system, and in the inactivation of CDKN2A. Novel ESFT biomarker genes identified in this study serve as a useful resource for future studies and in developing novel therapeutic strategies to improve the survival of patients with ESFT.

Pseudo-time marching schemes for inverse problems in structural health assessment and medical imaging

We propose a self-regularized pseudo-time marching strategy for ill-posed, nonlinear inverse problems involving recovery of system parameters given partial and noisy measurements of system response. While various regularized Newton methods are popularly employed to solve these problems, resulting solutions are known to sensitively depend upon the noise intensity in the data and on regularization parameters, an optimal choice for which remains a tricky issue. Through limited numerical experiments on a couple of parameter re-construction problems, one involving the identification of a truss bridge and the other related to imaging soft-tissue organs for early detection of cancer, we demonstrate the superior features of the pseudo-time marching schemes.

Evaluation of the Biocompatibility of Poly (ortho ester), Copolymer of ε-caprolactone/D,L-lactide and the Composite of Copolymer of ε-caprolactone/D,L-lactide and Tricalciumphosphate as Bone Filling Material

The purpose of this series of studies was to evaluate the biocompatibility of poly (ortho) ester (POE), copolymer of ε-caprolactone and D,L-lactide [P (ε-CL/DL-LA)] and the composite of P(ε-CL/DL-LA) and tricalciumphosphate (TCP) as bone filling material in bone defects. Tissue reactions and resorption times of two solid POE-implants (POE 140 and POE 46) with different methods of sterilization (gamma- and ethylene oxide sterilization), P(ε-CL/DL-LA)(40/60 w/w) in paste form and 50/50 w/w composite of 40/60 w/w P(ε-CL/DL-LA) and TCP and 27/73 w/w composite of 60/40 w/w P(ε-CL/DL-LA) and TCP were examined in experimental animals. The follow-up times were from one week to 52 weeks. The bone samples were evaluated histologically and the soft tissue samples histologically, immunohistochemically and electronmicroscopically. The results showed that the resorption time of gamma sterilized POE 140 was eight weeks and ethylene oxide sterilized POE 140 13 weeks in bone. The resorption time of POE 46 was more than 24 weeks. The gamma sterilized rods started to erode from the surface faster than ethylene oxide sterilized rods for both POEs. Inflammation in bone was from slight to moderate with POE 140 and moderate with POE 46. No highly fluorescent layer of tenascin or fibronectin was found in the soft tissue. Bone healing at the sites of implantation was slower than at control sites with the copolymer in small bone defects. The resorption time for the copolymer was over one year. Inflammation in bone was mostly moderate. Bone healing at the sites of implantation was also slower than at the control sites with the composite in small and large mandibular bone defects. Bone formation had ceased at both sites by the end of follow-up in large mandibular bone defects. The ultrastructure of the connective tissue was normal during the period of observation. It can be concluded that the method of sterilization influenced the resorption time of both POEs. Gamma sterilized POE 140 could have been suitable material for filling small bone defects, whereas the degradation times of solid EO-sterilized POE 140 and POE 46 were too slow to be considered as bone filling material. Solid material is difficult to contour, which can be considered as a disadvantage. The composites were excellent to handle, but the degradation time of the polymer and the composites were too slow. Therefore, the copolymer and the composite can not be recommended as bone filling material.

Scattering and Refraction as Contrast Mechanisms in X-Ray Imaging

Differentiation of various types of soft tissues is of high importance in medical imaging, because changes in soft tissue structure are often associated with pathologies, such as cancer. However, the densities of different soft tissues may be very similar, making it difficult to distinguish them in absorption images. This is especially true when the consideration of patient dose limits the available signal-to-noise ratio. Refraction is more sensitive than absorption to changes in the density, and small angle x-ray scattering on the other hand contains information about the macromolecular structure of the tissues. Both of these can be used as potential sources of contrast when soft tissues are imaged, but little is known about the visibility of the signals in realistic imaging situations. In this work the visibility of small-angle scattering and refraction in the context of medical imaging has been studied using computational methods. The work focuses on the study of analyzer based imaging, where the information about the sample is recorded in the rocking curve of the analyzer crystal. Computational phantoms based on simple geometrical shapes with differing material properties are used. The objects have realistic dimensions and attenuation properties that could be encountered in real imaging situations. The scattering properties mimic various features of measured small-angle scattering curves. Ray-tracing methods are used to calculate the refraction and attenuation of the beam, and a scattering halo is accumulated, including the effect of multiple scattering. The changes in the shape of the rocking curve are analyzed with different methods, including diffraction enhanced imaging (DEI), extended DEI (E-DEI) and multiple image radiography (MIR). A wide angle DEI, called W-DEI, is introduced and its performance is compared with that of the established methods. The results indicate that the differences in scattered intensities from healthy and malignant breast tissues are distinguishable to some extent with reasonable dose. Especially the fraction of total scattering has large enough differences that it can serve as a useful source of contrast. The peaks related to the macromolecular structure come to angles that are rather large, and have intensities that are only a small fraction of the total scattered intensity. It is found that such peaks seem to have only limited usefulness in medical imaging. It is also found that W-DEI performs rather well when most of the intensity remains in the direct beam, indicating that dark field imaging methods may produce the best results when scattering is weak. Altogether, it is found that the analysis of scattered intensity is a viable option even in medical imaging where the patient dose is the limiting factor.

Integration of miRNA and mRNA expression with DNA copy number of Ewing sarcoma cell lines

Ewing sarcoma is an aggressive and poorly differentiated malignancy of bone and soft tissue. It primarily affects children, adolescents, and young adults, with a slight male predominance. It is characterized by a translocation between chromosomes 11 and 22 resulting in the EWSR1-FLI1fusion transcription factor. The aim of this study is to identify putative Ewing sarcoma target genes through an integrative analysis of three microarray data sets. Array comparative genomic hybridization is used to measure changes in DNA copy number, and analyzed to detect common chromosomal aberrations. mRNA and miRNA microarrays are used to measure expression of protein-coding and miRNA genes, and these results integrated with the copy number data. Chromosomal aberrations typically contain also bystanders in addition to the driving tumor suppressor and oncogenes, and integration with expression helps to identify the true targets. Correlation between expression of miRNAs and their predicted target mRNAs is also evaluated to assess the results of post-transcriptional miRNA regulation on mRNA levels. The highest frequencies of copy number gains were identified in chromosome 8, 1q, and X. Losses were most frequent in 9p21.3, which also showed an enrichment of copy number breakpoints relative to the rest of the genome. Copy number losses in 9p21.3 were found have a statistically significant effect on the expression of MTAP, but not on CDKN2A, which is a known tumor-suppressor in the same locus. MTAP was also down-regulated in the Ewing sarcoma cell lines compared to mesenchymal stem cells. Genes exhibiting elevated expression in association with copy number gains and up-regulation compared to the reference samples included DCAF7, ENO2, MTCP1, andSTK40. Differentially expressed miRNAs were detected by comparing Ewing sarcoma cell lines against mesenchymal stem cells. 21 up-regulated and 32 down-regulated miRNAs were identified, includingmiR-145, which has been previously linked to Ewing sarcoma. The EWSR1-FLI1 fusion gene represses miR-145, which in turn targets FLI1 forming a mutually repressive feedback loop. In addition higher expression linked to copy number gains and compared to mesenchymal stem cells, STK40 was also found to be a target of four different miRNAs that were all down-regulated in Ewing sarcoma cell lines compared to the reference samples. SLCO5A1 was identified as the only up-regulated gene within a frequently gained region in chromosome 8. This region was gained in over 90 % of the cell lines, and also with a higher frequency than the neighboring regions. In addition, SLCO5A1 was found to be a target of three miRNAs that were down-regulated compared to the mesenchymal stem cells.

Ancylidae (Mollusca, Heterobranchia, Pulmonata, Basommatophora) do Estado do Rio de Janeiro, Brasil: morfologia, sistemática e distribuição geográfica

Os moluscos pateliformes de água doce da região Neotropical são comumente atribuídos a família Ancylidae sensu latum, abrangendo sete gêneros com pelo menos 13 espécies válidas e sete com identificação duvidosa. Os ancilídeos possuem pequenas dimensões, alcançam no máximo 15 mm de comprimento. Sua concha é frágil, composta por duas regiões, a protoconcha e a teleoconcha, as quais apresentam caracteres relevantes para a sistemática. Na parte mole as impressões musculares, a pigmentação do manto, o sistema reprodutor e a rádula são importantes para o estudo da família. Apesar de existirem vários registros de ocorrência para ancílideos no Estado do Rio de Janeiro (ERJ), existem poucos dados morfológicos. O principal objetivo deste estudo foi fornecer e ampliar as informações sobre a morfologia e distribuição geográfica das espécies de Ancylidae encontradas no ERJ. Os materiais utilizados foram procedentes de coletas próprias, material depositado em Coleções Científicas e dados de revisão bibliográfica. O estudo da morfologia comparada das conchas foi realizado com o auxílio de imagens de microscópio óptico e de varredura. Para a comparação das partes moles, os espécimes foram corados e dissecados sob lupa. Através da conquiliometria analisamos as diferenças inter e intrapopulacionais. Com este trabalho, a riqueza conhecida para Ancylidae no ERJ, aumentou de cinco para sete espécies: Burnupia sp., Ferrissia sp., Gundlachia radiata (Guilding, 1828),G. ticaga (Marcus & Marcus, 1962), Gundlachia sp., Hebetancylus moricandi (d`Orbigny, 1837) e Uncancylus concentricus (d`Orbigny, 1837). Gundlachia radiata e U. concentricus constituem novos registros para o ERJ, e G. radiata para a Região Sudeste. As três espécies com o maior número de registros de ocorrência no ERJ foram: G. ticaga (66%), Ferrissia sp. (37%) e Gundlachia sp. (18%). A ampla distribuição de G. ticaga pode ser devido à capacidade de suportar ambientes impactados. Em relação à morfologia, Burnupia sp. difere de Burnupia ingae Lanzer, 1991, única espécie deste gênero descrita para o Brasil, por apresentar diferenças na microescultura da concha e também na forma das impressões musculares. Ferrissia sp. difere de F. gentilis Lanzer, 1991, devido a diferenças na microescultura apical e número de cúspides no dente central da rádula. Gundlachia sp. é diferente de G. ticaga e G. radiata, por apresentar a abertura da concha mais arredondada, ápice mais recurvado, ultrapassando a borda da concha, pontuações irregulares em toda a protoconcha e forma dos músculos adutores anterior direito e posterior mais elíptica. A morfologia interna também mostra diferenças entre Gundlachia sp. e G. ticaga, como o apêndice terminal do útero e o número de folículos do ovoteste. Através das análises conquiliométricas, constatamos para os gêneros Burnupia, Ferrrissia e Gundlachia, que os índices morfométricos se mostraram melhores que as medidas lineares para a discriminação das espécies, provavelmente porque esses índices diminuem o efeito da amplitude de tamanho das conchas, que são fortemente influenciadas pelas variações ecofenotípicas. Contudo, os caracteres diagnósticos das conchas e das partes moles (impressões musculares) são indispensáveis para a identificação dos gêneros e espécies de Ancylidae. Palavras-chave: Mollusca. Moluscos de água doce. Morfologia. Distribuição geográfica. Estado do Rio de Janeiro.uscos.

Estudo clínico randomizado duplo cego comparando duas técnicas de plicatura nasal após osteotomias tipo Le Fort I

A correção de deformidades esqueléticas da face por meio de um tratamento ortodôntico-cirúrgico tornou-se uma opção segura e previsível. Os movimentos ósseos são milimetricamente calculados e executados cirurgicamente, assim como a oclusão é meticulosamente engrenada através dos movimentos ortodônticos. Os efeitos que os tecidos moles sofrem com as cirurgias ortognáticas são, no entanto, menos previsíveis, e apesar do principal objetivo da cirurgia ortognática ser uma melhora funcional, o componente estético é sem dúvida de extrema importância. Em especial, a região de base alar apresenta resultados muito variáveis, a despeito dos bons resultados esqueléticos atingidos. O objetivo deste estudo foi comparar 2 diferentes tipos de sutura utilizados na região de base do nariz, e observar qual tipo apresenta um resultado que melhor acompanhe os movimentos realizados pelo tecido esquelético. Trinta e cinco pacientes foram aleatoriamente distribuídos em 2 grupos. O grupo 1 funcionou como controle e os pacientes receberam a plicatura nasal intra-oral, que é o tipo de plicatura nasal mais descrito na literatura. Já os pacientes do grupo 2 receberam plicatura nasal extra-oral. Para análise estatística foram calculadas as médias e desvios padrões dos grupos, e a hipótese nula de que não havia diferença entre os 2 grupos foi testata com o teste T de Student. Em ambos os grupos ocorreu um alargamento da base do nariz, porém a média de alargamento do grupo 1 foi de 2,50 milímetros (mm), enquanto que a média de alargamento do grupo 2 foi de 1,26 mm. Além disso, o desvio padrão foi menor para o grupo 2, e a hipótese nula foi rejeitada (p<0,05), demonstrando que a diferença entre os grupos foi estatisticamente significativa. Pôde-se concluir que quando objetiva-se um controle mais previsível e rigoroso da base do nariz, a plicatura nasal extra-oral cumprirá melhor esta função.

Avaliação da estabilidade da cirurgia de avanço mandibular através da superposição de modelos tridimensionais

Embora a cirurgia de avanço mandibular seja considerada um procedimento altamente estável, existem algumas preocupações clínicas em relação a mudanças nos côndilos e nos segmentos proximais, que podem levar a recidiva sagital e abertura de mordida. A avaliação dos resultados da cirurgia através de ferramentas de geração e superposição de modelos virtuais tridimensionais (3D) permite a identificação e quantificação dos deslocamentos e remodelação óssea que podem ajudar a explicar as interações entre os componentes dentários, esqueléticos e de tecido mole que estão relacionados a resposta ao tratamento. Este estudo observacional prospectivo avaliou, através de tomografia computadorizada de feixe cônico (CBCT), mudanças na posição/remodelação 3D dos ramos mandibulares, côndilos e mento. Assim, exames CBCT de 27 pacientes foram adquiridos antes da cirurgia (T1), imediatamente após a cirurgia(T2), e 1 ano após a cirurgia(T3). Uma técnica automática de superposição na base do crânio foi utilizada para permitir a avaliação das mudanças ocorridas nas regiões anatômicas de interesse (RAI). Os deslocamentos foram visualizados e quantificados em mapas coloridos 3D através da ferramenta de linha de contorno (ISOLINE). Pelo teste t pareado compararam-se as mudanças entre T1-T2 e T2-T3. O coeficiente de correlação de Pearson verificou se os deslocamentos ocorridos nas RAI foram correlacionados entre si e entre os tempos de avaliação. O nível de significância foi determinado em 0,05. O avanço mandibular médio foi de 6,813,2mm em T2 e 6,363,41mm em T3 (p=0,13). Entre T2 e T3, a posição do mento variou positivamente (≥2mm) em 5 pacientes negativamente em 7. 12% dos pacientes sofreram recidivas ≥4mm. Para todas as outras RAI avaliadas, apenas a porção inferior dos ramos (lado direito - 2,342,35mm e lado esquerdo 2,972,71mm) sofreram deslocamentos médios >2mm com a cirurgia. No acompanhamento em longo prazo, esse deslocamento lateral da porção inferior dos ramos foi mantido (lado direito - 2,102,15mm, p=0,26; e lado esquerdo -2,762,80, p=0,46), bem como todos os outros deslocamentos observados (p>0,05). As mudanças na posição do mento foram correlacionadas a adaptações pós-cirúrgicas nos bordos posteriores dos ramos (esquerdo r=-0,73 e direito r=-0,68) e côndilos (esquerdo r=-0,53 e direito r=-0,46). Os deslocamentos médios sofridos pelas estruturas do lado esquerdo foram suavemente maiores do que no direito. Correlações dos deslocamentos ocorridos entre T1-T2 e T2-T3 mostraram que: os deslocamentos dos côndilos esquerdos com a cirurgia foram negativamente correlacionados às adaptações pós-cirúrgicas destes (r=-0,51); e que o deslocamento da porção superior do ramo esquerdo com a cirurgia foi correlacionado à adaptação pós-cirúrgica ocorrida nos bordos posteriores (r=0,39) e côndilos do mesmo lado (r=0,39). Pode-se concluir que: (1) os deslocamentos causados pela cirurgia foram de modo geral estáveis no acompanhamento de 1 ano, mas identificou-se uma considerável variação individual; (2) as mudanças pós-cirúrgicas na posição do mento foram correlacionadas a adaptações sofridas pelos côndilos e bordos posteriores dos ramos; e que (3) deslocamentos suavemente maiores causados pela cirurgia nas estruturas do lado esquerdo levaram a maiores adaptações pós-cirúrgicas no segmento proximal deste lado.

Avaliação da fidelidade da referência externa em tecidos moles na cirurgia ortognática da maxila

Esse trabalho teve o objetivo de analisar a fidelidade da referência externa em tecidos moles no auxílio do posicionamento vertical da maxila. Foram selecionados 40 pacientes portadores de deformidade dentofacial e submetidos à osteotomia total da maxila. Os indivíduos foram divididos em 2 grupos no intuíto de avaliar duas técnicas de referência externa: a utilização da sutura em tecidos moles e o uso do fio de Kirschner. Esta última foi utilizada como a técnica do grupo-controle. Os dados foram colhidos em duas fases. Na primeira delas, foi realizada a mensuração da posição vertical da maxila antes da osteotomia Le Fort I e após a fixação da maxila, utilizando a referência externa. A partir desses números, foi obtida a alteração vertical de cada caso, colhida durante a cirurgia. Na segunda fase da coleta de dados, foram realizadas mensurações verticais da maxila baseadas nas radiografias cefalométricas pré e pós-operatórias. Assim, foi obtido o valor da alteração vertical de cada caso, baseado na documentação radiográfica. Após esta etapa, foi calculada a diferença entre a alteração vertical obtida durante a cirurgia e a alteração vertical colhida a partir das radiografias. Dessa forma, foram obtidos valores que correspondem às imperfeições no posicionamento vertical da maxila de cada paciente, tendo como base a posição do incisivo central superior. Os resultados foram comparados e analisados estatisticamente. A média aritmética da precisão no posicionamento vertical da maxila no grupo-controle foi de 0,52mm e do grupo da referência em tecidos moles foi de 0,65mm. A aplicação do teste t de Student a 5% revelou que não houve diferença estatística significativa entre o grau de precisão das duas técnicas de referência externa (P=0,429). Como conclusão, observou-se que as duas técnicas foram eficazes no auxílio ao posicionamento vertical da maxila e que a referência externa em tecidos moles apresentou um grau de precisão semelhante ao valor obtido com a técnica do fio de Kirschner.