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Hyperextension deformity of the metacarpophalangeal joint of the thumb causes pain and loss of function. Although many treatments have been proposed, none of them are universally accepted as ideal. The authors report a study of 12 symptomatic hyperextension deformities of the thumb metacarpophalangeal joint in 10 patients who underwent surgical correction. The purpose of this study was to describe a new technique of tenodesis of the thumb metacarpophalangeal joint using the extensor pollicis brevis tendon. The technique consists of extensor pollicis brevis tenotomy at the wrist and tendon transfer through two bone tunnels to the palmar aspect of the metacarpophalangeal joint before metacarpal fixation with a flexor tenodesis effect. Correction of hyperextension and range of motion were assessed. Functional changes were evaluated by Quick Disabilities of the Arm, Shoulder, and Hand score, pain visual analogue scale, Kapandji opposition scheme, and pinch strength. The Wilcoxon test was used for statistical analysis. Mean preoperative and postoperative metacarpophalangeal joint hyperextension deformities were +50.83 ± 5.57 degrees and -17.91 ± 7.82 degrees, respectively. Thumb opposition improved by one point on Kapandji's scheme. Mean perceived pain decreased from 7.66 to 1.16. On average, the Quick Disabilities of the Arm, Shoulder, and Hand score was reduced by 34.4 points and pinch strength increased by 50.42 percent. The authors found that extensor pollicis brevis transosseous tenodesis is a safe and minimally invasive method for successfully correcting the functionality and cosmetic appearance of metacarpophalangeal joint hyperextension deformities in posttraumatic and trapeziometacarpal osteoarthritis cases. The patients retained functional active flexion, even in deformities greater than 40 degrees.Therapeutic, IV.

The scapholunate interosseous ligament (SLIL) plays a fundamental role in stabilizing the wrist bones, and its disruption is a frequent cause of wrist arthrosis and disfunction. Traditionally, this structure is considered to be a variety of fibrocartilaginous tissue and consists of three regions: dorsal, membranous and palmar. Despite its functional relevance, the exact composition of the human SLIL is not well understood. In the present work, we have analyzed the human SLIL and control tissues from the human hand using an array of histological, histochemical and immunohistochemical methods to characterize each region of this structure. Results reveal that the SLIL is heterogeneous, and each region can be subdivided in two zones that are histologically different to the other zones. Analysis of collagen and elastic fibers, collagens types I, III and IV, proteoglycans, glycoproteins and versican confirmed that the different regions can be subdivided in two zones that have their own structure and composition. The first part of the dorsal region (zone D1) resembles the control tendons and ligaments, whereas the rest of the SLIL are more similar to the control articular cartilage, especially the first part of the membranous region (zone M1). Cells showing a chondrocyte-like phenotype as determined by S100 were more abundant in M1, whereas the zone containing more CD73-positive stem cells was D2. These results confirm the heterogeneity of the human SLIL and could contribute to explain why certain zones of this structure are more prone to structural damage and why other zones have specific regeneration potential.

Human Wharton's jelly stem cells (HWJSC) can be efficiently isolated from the umbilical cord, and numerous reports have demonstrated that these cells can differentiate into several cell lineages. This fact, coupled with the high proliferation potential of HWJSC, makes them a promising source of stem cells for use in tissue engineering and regenerative medicine. However, their real potentiality has not been established to date. In the present study, we carried out a systematic review to determine the multilineage differentiation potential of HWJSC. After a systematic literature search, we selected 32 publications focused on the differentiation potential of these cells. Analysis of these studies showed that HWJSC display expanded differentiation potential toward some cell types corresponding to all three embryonic cell layers (ectodermal, mesodermal, and endodermal), which is consistent with their constitutive expression of key pluripotency markers such as OCT4, SOX2, and NANOG, and the embryonic marker SSEA4. We conclude that HWJSC can be considered cells in an intermediate state between multipotentiality and pluripotentiality, since their proliferation capability is not unlimited and differentiation to all cell types has not been demonstrated thus far. These findings support the clinical use of HWJSC for the treatment of diseases affecting not only mesoderm-type tissues but also other cell lineages. Impact statement Human Wharton's jelly stem cells (HWJSC) are mesenchymal stem cells that are easy to isolate and handle, and that readily proliferate. Their wide range of differentiation capabilities supports the view that these cells can be considered pluripotent. Accordingly, HWJSC are one of the most promising cell sources for clinical applications in advanced therapies.

Several models of bioartificial human urothelial mucosa (UM) have been described recently. In this study, we generated novel tubularized UM substitutes using alternative sources of cells. Nanostructured fibrin–agarose biomaterials containing fibroblasts isolated from the human ureter were used as stroma substitutes. Then, human Wharton jelly mesenchymal stromal cells (HWJSC) were used to generate an epithelial-like layer on top. Three differentiation media were used for 7 and 14 days. Results showed that the biofabrication methods used here succeeded in generating a tubular structure consisting of a stromal substitute with a stratified epithelial-like layer on top, especially using a medium containing epithelial growth and differentiation factors (EM), although differentiation was not complete. At the functional level, UM substitutes were able to synthesize collagen fibers, proteoglycans and glycosaminoglycans, although the levels of control UM were not reached ex vivo. Epithelial differentiation was partially achieved, especially with EM after 14 days of development, with expression of keratins 7, 8, and 13 and pancytokeratin, desmoplakin, tightjunction protein-1, and uroplakin 2, although at lower levels than controls. These results confirm the partial urothelial differentiative potential of HWJSC and suggest that the biofabrication methods explored here were able to generate a potential substitute of the human UM for future clinical use., CTS-115 Tissue Engineering Group and by the Spanish Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Ministry of Science and Innovation, Instituto de Salud Carlos III, grant FIS PI21/0981 (cofinanced by FEDER funds, European Union).

Background Flexor retinaculum reconstruction techniques or simply Flexor Retinaculum Z-lengthening have been proposed to preserve Flexor Retinaculum continuity after carpal tunnel release. Their effectiveness is based solely on symptom relief. There has been no analysis of the effects on intra-carpal tunnel pressure of Flexor Retinaculum-lengthening techniques. Objective was to compare intra-carpal tunnel pressure outcomes between complete division and Z-lengthening of the Retinaculum in a cadaveric model of carpal tunnel release. Methods Experimental study of carpal tunnel pressure after surgical Flexor Retinaculum modification in 10 fresh-frozen forearm and hand cadaveric specimens. The Kyphon™ Balloon Kyphoplasty system was used to measure the pressure before and after infusing 1, 2, 3, 4 and 5 ml of saline solution when untreated (Flexor Retinaculum continuity stage I), when Z-lengthened (Flexor Retinaculum continuity stage II), and after complete Flexor Retinaculum division (Flexor Retinaculum continuity stage III). Finding Intra-carpal tunnel pressure increased with larger volume of infused saline solution, although mean pressures were lower after Z lengthening or complete division of the Retinaculum than at baseline. Analysis of linear regression coefficients indicated significant differences as a function of FR continuity stage (F(2,18) = 18.38, p 0.001), while the Bonferroni test revealed significant differences in slopes between stages I and III (p = 0.003), between stages I and II (p 0.02), but not between stages II and III (p 0.05). Interpretation The effectiveness of carpal tunnel release and the reduction in intra-carpal tunnel pressures obtained by Z-lengthening of the FR were similar to those observed after its complete division, while preserving FR continuity.

Objective: To determine and compare specific factors that could be associated and predictive with successful prosthetic rehabilitation in major lower-limb amputations. Methods: A 15-year long (2000-2014) retrospective observational cohort study was conducted. Two different criteria were used to define successful prosthetic rehabilitation: (1) the ability to walk at least 45 m, regardless of assistive devices; and (2) walking >45 m without other ambulatory aids than one cane (if required). Age, gender, comorbidities, cause and level of amputation, stump characteristics, ulcers in the preserved limb, and time between surgery and physical therapy were examined as predictors of successful prosthetic rehabilitation. Results: A total of 169 patients (61.60±15.9 years) were included. Regarding walking ability with or without walking aids, the presence of ulcers in the preserved limb was individually associated with failed prosthetic rehabilitation (p < 0.001), while being male (OR = 0.21; 95%CI = 0.06-0.80) and transtibial level of amputation (OR = 6.73; 95%CI = 1.92-23.64) were identified as independent predictors of failure and success, respectively. Regarding the criterion of successful rehabilitation, a shorter time until rehabilitation was individually associated with improved walking ability (p < 0.013), while failure could be predicted by comorbidities (OR = 0.48; 95%CI = 0.29---0.78) and age groups of 65---75 years old (OR = 0.19; 95%CI = 0.05-0.78) and over 75 years old (OR = 0.19; 95%CI = 0.04-0.91). Conclusions: Regarding walking ability with or without walking aids, male gender and transtibiallevel of amputation are independently associated with failure and success respectively, whereasolder age and comorbidities can predict failed prosthetic rehabilitation when assistive walking devices are considered. Future prospective cohort studies are needed to confirm these findings.

Current tissue engineering technology focuses on developing simple tissues, whereas multilayered structures comprising several tissue types have rarely been described. We developed a highly biomimetic multilayered palate substitute with bone and oral mucosa tissues using rabbit cells and biomaterials subjected to nanotechnological techniques based on plastic compression. This novel palate substitute was autologously grafted in vivo, and histological and histochemical analyses were used to evaluate biointegration, cell function, and cell differentiation in the multilayered palate substitute. The three-dimensional structure of the multilayered palate substitute was histologically similar to control tissues, but the ex vivo level of cell and tissue differentiation were low as determined by the absence of epithelial differentiation although cytokeratins 4 and 13 were expressed. In vivo grafting was associated with greater cell differentiation, epithelial stratification, and maturation, but the expression of cytokeratins 4, 13, 5, and 19 at did not reach control tissue levels. Histochemical analysis of the oral mucosa stroma and bone detected weak signals for proteoglycans, elastic and collagen fibers, mineralization deposits and osteocalcin in the multilayered palate substitute cultured ex vivo. However, in vivo grafting was able to induce cell and tissue differentiation, although the expression levels of these components were always significantly lower than those found in controls, except for collagen in the bone layer. These results suggest that generation of a full-thickness multilayered palate substitute is achievable and that tissues become partially differentiated upon in vivo grafting.

Resumen Introduccion El papel de la cirugia robotica esta claramente establecido en diversas especialidades como Urologia o Cirugia General, pero no asi en otras como Neurocirugia u Otorrinolaringologia, y en el caso concreto de la Cirugia de base de craneo, apenas ha pasado de una fase experimental. Objetivo Investigar las posibilidades de la aplicacion del robot quirurgico da Vinci en cirugia transoral de base de craneo comparandola con la experiencia de los autores en cirugia endoscopica transnasal convencional de la misma region. Metodos se llevo a cabo un abordaje transoral transpalatino a la rinofaringe y la base del craneo medial en 4 cabezas de cadaver criopreservadas. Se empleo el robot da Vinci, con endoscopio de 30° y 12 mm de grosor, con doble camara e iluminacion doble, pinza de Maryland en el terminal izquierdo y tijera curva en el derecho, ambos de 8 mm de grosor. El fresado oseo se realizo manualmente. Para el estudio anatomico de la region a abordar se emplearon cortes axiales de 0,5 cm de grosor de una cabeza de cadaver plastinada. Resultados Con los terminales del robot se alcanzaron con relativa facilidad diversas estructuras de la base del craneo a distintos niveles de profundidad. Conclusiones La cirugia robotica transoral con el sistema da Vinci aporta posibles ventajas sobre la cirugia endoscopica transnasal convencional en el abordaje quirurgico de esta region

Although several studies have been published regarding the morphology and anatomical variations of the human shoulder joint, most have dealt with adult individuals. Those looking into the development of the joint have been focused on specific structures or have observed specimens in advanced gestational stages. The goal of this paper is to perform a complete analysis of the embryonic and early fetal development of the elements in the shoulder joint, and to clarify some contradictory data in the literature. In our study, serial sections of 32 human embryos (Carnegie stages 16-23) and 26 fetuses (9-13 weeks) were analyzed. The chondrogenic anlagen of the humerus and the medial border of the scapula can be observed from as early as Carnegie stage 17, whereas that of the rest of the scapula appears at stage 18. The osteogenic process begins in week 10 for the humeral head and week 11 for the scapula. At stage 19 the interzone becomes apparent, which will form the glenohumeral joint. In the next stage the glenohumeral joint will begin delaminating and exhibiting a looser central band. Denser lateral bands will join the humeral head (caput humeri) and the margins of the articular surface of the scapula, thus forming the glenoid labrum, which can be fully appreciated by stage 22. In 24-mm embryos (stage 21) we can observe, for the first time, the long head of the biceps tendon (which is already inserted in the glenoid labrum by week 9), and the intertubercular sulcus, whose depth is apparent since week 12. Regarding ligamentous structures, the coracohumeral ligament is observed at the end of Carnegie stage 23, whereas the primitive glenohumeral ligament already appeared in week 10. The results of this study provide a detailed description of the morphogenesis, origin and chronological order of appearance of the main intrinsic structures of the human shoulder joint during late embryonic and early fetal development. We expect these results to help explain several functional aspects of the shoulder joint, and to clarify some contradictory data in the literature regarding this complex anatomical and biomechanical structure, helping future researchers in their efforts.

Objectives To analyze the association of sarcopenia, obesity, and sarcopenic obesity (SO) with fear of falling (FoF) and balance confidence in a Spanish sample of middle-aged and older community-dwelling women. Study design and outcome measures A total of 235 women (69.21 ± 7.56 years) participated in this study. Body composition (bioelectrical impedance analysis), hand-grip strength, and physical performance (gait speed) were evaluated for the diagnosis of sarcopenia, obesity, and SO. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. The Activities-Specific Balance Confidence Scale (ABC) and the Falls Efficacy Scale-International (FES-I) were employed to assess FoF and balance confidence, respectively. Scores of >26 on the FES-I and Results 27.23% and 18.72% of women presented with sarcopenia and SO, respectively. Gait speed, body mass index (BMI), and fall history were independently associated with ABC score (adjusted-R 2 = 0.152) and fall risk (ABC) (adjusted-R 2 = 0.115). FES-I score was independently associated (adjusted-R 2 = 0.193) with fall history, gait speed, BMI, and depression, which, together with obesity (BMI) and SO, remained independent factors for fall risk measured as FES-I score (adjusted-R 2 = 0.243). Conclusion In community-dwelling middle-aged and older Spanish women, BMI, gait speed, and fall history were independently associated with FoF, balance confidence, and fall risk. Depression was related only to FoF, and, together with obesity (BMI) and SO, was an independent predictor of fall risk as assessed by the FES-I.

Several studies have focused on the cartilaginous, articular, and ligamentous development of the craniovertebral joint (CVJ), but there are no unifying criteria regarding the origin and morphogenetic timetable of the structures that make up the CVJ. In our study, serial sections of 53 human embryonic (n = 27) and fetal (n = 26) specimens from O'Rahilly stages 17–23 and 9–13 weeks, respectively, have been analyzed. Our results demonstrate that the chondrification of the pars basioccipitalis and exoccipitalis becomes observable at stage 19, and all future bones in the CVJ are in their cartilaginous form except for the future odontoid process. In addition, two chondrification centers appear for the body of the axis. From stage 21, the apical, alar, and transverse atlantal ligaments begin to acquire a ligamentous structure and the odontoid process initiates its chondrogenic phase. Stage 22 witnesses the first signs of the articular cavities of the atlanto-occipital joint, and by stage 23 all joints have cavities except for the transverse-odontoid joint, which will wait until week 9. In week 10, the ossification of the basilar part of the occipital bone begins, followed by the rest of the structures except for the odontoid process, which will start at week 13, thus completing the osteogenesis of all bones in the CVJ. The results of this study could help in establishing the anatomical basis of the normally functioning CVJ and for detecting its related pathologies, abnormalities, and malformations. Clin. Anat. 27:337–345, 2014. © 2014 Wiley Periodicals, Inc.

Scleral defects can result as a consequence of trauma, infectious diseases or cancer and surgical repair with allogeneic scleral grafts can be required. However, this method has limitations and novel alternatives are needed. Here, the efficacy of acellular nanostructured fibrin-agarose hydrogel-based substitutes (NFAH) in the repair of scleral defects in rabbits was studied. For this, scleral defects of 5-mm diameter were made on 18 adult-male New Zealand rabbits and repaired with acellular NFAH, NFAH crosslinked with genipin (NFAH-GP) or glutaraldehyde (NFAH-GA), allogeneic scleral grafts as control (C-CTR) or not repaired (negative control N-CTR) (n = 3 each). Macroscopic and histological analyses were performed after 40-days. Macroscopy confirmed the repair of all defects in a comparable manner than the C-CTR. Histology showed no degradation nor integration in C-CTR while NFAH-GP and NFAH-GA biomaterials were encapsulated by connective and inflammatory tissues with partial biodegradation. The NFAH were fully biodegraded and replaced by a loose connective tissue and sclera covering the defects. This in vivo study demonstrated that the NFAH are a promising biocompatible and pro-regenerative alternative to the use of allogeneic cadaveric grafts. However, large defects and long-term studies are needed to demonstrate the potential clinical usefulness of these substitutes.

Because of the pleiotropic effects of statins, it may potentially be used as a locoregional adjuvant in vascular revascularization, tissue engineering, and regenerative procedures. Electron probe X-ray microanalyses and oligonucleotide microarrays were used to identify the global effects of micromolar concentrations of atorvastatin on the gene expression and cell viability of endothelial cells in different states of lysophosphatidic acid (LPA)-induced activation. Treatment with 1-μM atorvastatin for 24 hours significantly reduced the viability of human vascular endothelial cells (HUVECs). However, the same treatment of LPA-preactivated HUVECs produced elevated cell viability levels and an optimal vascular gene expression profile, including endothelial nitric oxide synthase overexpression, endothelin-1 repression, an anti-inflammatory genetic pattern, and upregulation of molecules involved in maintaining the endothelial barrier (vascular endothelial cadherin, claudin 5, tight junction protein 1, integrin β4). The atorvastatin treatment also produced a repression of microRNA 21 and genes involved in cell proliferation and neointimal formation (vascular endothelial growth factor [VEGF] A, VEGF receptor 1, VEGFC). Results obtained suggest that micromolar atorvastatin therapy can enhance global endothelial function, but its effects on cell viability vary according to the baseline state of cell activation (preactivated, postactivated, or not activated). Preactivation with LPA protects HUVECs against atorvastatin-induced apoptosis and delivers optimal levels of cell viability and functionality.

The development of the human wrist joint has been studied widely, with the main focus on carpal chondrogenesis, ligaments and triangular fibrocartilage. However, there are some discrepancies concerning the origin and morphogenetic time-table of these structures, including nerves, muscles and vascular elements. For this study we used serial sections of 57 human embryonic (n = 30) and fetal (n = 27) specimens from O’Rahilly stages 17–23 and 9–14 weeks, respectively. The following phases in carpal morphogenesis have been established: undifferentiated mesenchyme (stage 17), condensated mesenchyme (stages 18 and 19), pre-chondrogenic (stages 19 and 20) and chondrogenic (stages 21 and over). Carpal chondrification and osteogenic processes are similar, starting with capitate and hamate (stage 19) and ending with pisiform (stage 22). In week 14, a vascular bud penetrates into the lunate cartilaginous mold, early sign of the osteogenic process that will be completed after birth. In stage 18, median, ulnar and radial nerves and thenar eminence appear in the hand plate. In stage 21, there are indications of the interosseous muscles, and in stage 22 flexor digitorum superficialis, flexor digitorum profundus and lumbrical muscles, transverse carpal ligament and collateral ligaments emerge. In stage 23, the articular disc, radiocarpal and ulnocarpal ligaments and deep palmar arterial arch become visible. Radiate carpal and interosseous ligaments appear in week 9, and in week 10, dorsal radiocarpal ligament and articular capsule are evident. Finally, synovial membrane is observed in week 13. We have performed a complete analysis of the morphogenesis of the structures of the human wrist joint. Our results present new data on nervous and arterial elements and provide the basis for further investigations on anatomical pathology, comparative morphology and evolutionary anthropology.

The beneficial effects of atorvastatin are based on both cholesterol-dependent and independent mechanisms. The latter probably include the ability of the estatin to enhance the expression of endothelial nitric oxide synthase (eNOS) and to cause a vasodilatation. In turn, the antioxidant and anti-inflammatory actions of melatonin are related to its vascular protection. In the present study, we investigated the efficacy of the combination of melatonin plus atorvastatin against endothelial cell damage induced by inflammation and oxidative stress injury. Human umbilical vein endothelial cells (HUVEC) were cultured with bacterial lipopolysaccharide (LPS) in the presence or absence of melatonin and/or atorvastatin. LPS inhibited eNOS mRNA and protein expression, which was reversed by atorvastatin and, to a lesser extent, by melatonin. Together, melatonin + atorvastatin induced higher eNOS protein expression than either compound alone. Melatonin, but not atorvastatin, reduced free radical generation, lipid peroxidation, and interleukin-6 levels induced by LPS. In the presence of atorvastatin, the effects of melatonin were maintained or even improved. These data suggest that melatonin improves the beneficial effects of atorvastatin and reduces its side effects in endothelial cells during inflammation and under conditions of oxidative stress.

Aim The aim of this study has been to evaluate the relevance of gross human anatomy in daily clinical practice and to compare it to that of other basic sciences (biochemistry, bioethics, cytohistology, microbiology, pharmacology, physiology, psychology). Materials and methods A total of 1250 questionnaires were distributed among 38 different medical speciality professionals. Answers were analyzed taking into account speciality (medical, surgery and others), professional status (training physician or staff member) and professional experience. Results The response rate was 42.9% ( n = 536). Gross human anatomy was considered the most relevant basic discipline for surgical specialists, while pharmacology and physiology were most relevant for medical specialists. Knowledge of anatomy was also considered fundamental for understanding neurological or musculoskeletal disorders. In undergraduate programmes, the most important focuses in teaching anatomy were radiological, topographical and functional anatomy followed by systematic anatomy. In daily medical practice anatomy was considered basic for physical examination, symptom interpretation and interpretation of radiological images. When professional status or professional experience was considered, small variations were shown and there were no significant differences related to gender or community. Conclusion Our results underline the relevance of basic sciences (gross anatomy, physiology, and pharmacology) in daily professional activity. Evidence-based studies such as ours, lend greater credibility and objectivity to the role of gross anatomy in the undergraduate training of health professionals and should help to establish a more appropriate curriculum for future professionals.

Se describe la primera versión del Plan de Estudios 2010 de Graduado en Medicina, aprobado en Junta de Facultad.

We evaluated the cytotoxic effects of four prostaglandin analogs (PGAs) used to treat glaucoma. First we established primary cultures of conjunctival stromal cells from healthy donors. Then cell cultures were incubated with different concentrations (0, 0.1, 1, 5, 25, 50 and 100%) of commercial formulations of bimatoprost, tafluprost, travoprost and latanoprost for increasing periods (5 and 30 min, 1 h, 6 h and 24 h) and cell survival was assessed with three different methods: WST-1, MTT and calcein/AM-ethidium homodimer-1 assays. Our results showed that all PGAs were associated with a certain level of cell damage, which correlated significantly with the concentration of PGA used, and to a lesser extent with culture time. Tafluprost tended to be less toxic than bimatoprost, travoprost and latanoprost after all culture periods. The results for WST-1, MTT and calcein/AM-ethidium homodimer-1 correlated closely. When the average lethal dose 50 was calculated, we found that the most cytotoxic drug was latanoprost, whereas tafluprost was the most sparing of the ocular surface in vitro. These results indicate the need to design novel PGAs with high effectiveness but free from the cytotoxic effects that we found, or at least to obtain drugs that are functional at low dosages. The fact that the commercial formulation of tafluprost used in this work was preservative-free may support the current tendency to eliminate preservatives from eye drops for clinical use., This study was supported by the Spanish Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I) from the Spanish Ministry of Economy and Competitiveness (Instituto de Salud Carlos III), grants FIS PI11/1582 and FIS PI14/0955 (co-financed by FEDER funds, European Union) and by Grant P10-CTS-6060 from the Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucia, Spain (Proyectos de Excelencia).

The origin of the styloglossus muscle was histologically studied bilaterally in nine human fetuses (18 sides). In all cases, the muscle originated in Reichert's cartilage, which gives rise to the temporal styloid process. We identified three types of variation: type A, an accessory muscle fascicle originating from the mandibular angle, found in 7 cases (12 sides); type B, where the styloglossus muscle was attached to the mandibular angle by fibrous tracts, found in three cases (4 sides); and type C, where an accessory muscle fascicle arose from the fibrous tract connecting Reichert's cartilage to the mandibular angle; found in one case. In all cases (2 sides), the styloglossus muscle was innervated by the hypoglossal nerve. Relationships between the styloglossus muscle and vasculonervous elements of the prestyloid and retrostyloid spaces were analysed.

The juxtaoral organ was studied using light microscopy in 55 human embryos and 90 fetuses at different stages of development. The juxtaoral organ arises from the epithelium at the bottom of the transverse opening of the primitive mouth during O'Rahilly stage 16 and becomes detached from the epithelium after O'Rahilly stage 18. The juxtaoral organ is innervated by the buccal nerve from O'Rahilly stage 20 onward, and its connective tissue capsule is clearly visible after week 11 of development. This study enabled us to describe three main periods of juxtaoral organ development: (1) the period of epithelial condensation and invagination, at O'Rahilly stages 16–17; (2) the period during which the juxtaoral organ becomes detached from the oral epithelium and is innervated, at O'Rahilly stages 18–23; and (3) the period during which the connective tissue capsule is formed, after week 11 of development. We also analysed the juxtaoral organ of five additional fetuses by immunohistochemistry with anti-NF-200 to verify their innervation. The results show that the juxtaoral organ may have a function in the mechanical activity of the region.

The role of robotic surgery is well established in various specialties such as urology and general surgery, but not in others such as neurosurgery and otolaryngology. In the case of surgery of the skull base, it has just emerged from an experimental phase.To investigate possible applications of the da Vinci surgical robot in transoral skull base surgery, comparing it with the authors' experience using conventional endoscopic transnasal surgery in the same region.A transoral transpalatal approach to the nasopharynx and medial skull base was performed on 4 cryopreserved cadaver heads. We used the da Vinci robot, a 30° standard endoscope 12mm thick, dual camera and dual illumination, Maryland forceps on the left terminal and curved scissors on the right, both 8mm thick. Bone drilling was performed manually. For the anatomical study of this region, we used 0.5cm axial slices from a plastinated cadaver head.Various skull base structures at different depths were reached with relative ease with the robot terminalsTransoral robotic surgery with the da Vinci system provides potential advantages over conventional endoscopic transnasal surgery in the surgical approach to this region.

Introduction: Left Ventricle Postinfarction Pseudoaneurysm (LVPS)—false aneurysm occurs after a free-wall rupture contained by the adjacent pericardium. LVPS lacks the normal structure of the ventricular wall and disrupts the normal chamber anatomy. However, the natural history, clinical presentation and surgical outcome are still unclear. For that reason, it is necessary to describe the most relevant anatomical characteristics of LVPS and the appropriate surgical strategies currently applied. Methods: We reviewed the anatomical characteristics of several patients diagnosed of LVPS and the surgical technique performed. In this work two different anatomical types of LVPS are described in detail, with the surgical and structural implications for left ventricle reconstruction. Results: There are two different anatomical forms of LVPS: 1) Typical pseudoaneurysm, with a small gateway neck between the Left Ventricle and the false aneurysm chamber (Figure 1(A)); 2) Atypical pseudoaneurysm, in which the anatomical defect is bigger, without well-defined edges, extends over a large segment of infarcted and thinned myocardial tissue. In both cases, the therapeuticstargets and the surgical techniques used were directed to restore the normal geometry ofLeft Ventricle, keeping the optimal mitral valve function. Conclusions: The surgical key-step is to preserve or to remodel the ventricular chamber anatomy. This fact restores the ventricular geometry, not only removing the wall discontinuity that generated the pseudoaneurysm. Nevertheless, final prognosis depends on the underlying ischemic cardiomyopathy and mechanical complications, such us mitral regurgitation or ventricular septal defect. No data (2014) UEM

A great deal of research has been published on the development of the human temporomandibularjoint (TMJ). However, there is some discordance about its morphological timing. The most controversial aspects concern the moment of the initial organization of the condyle and the squamous part of the temporal bone, the articular disc and capsule and also the cavitation and onset of condylar chondrogenesis. Serial sections of 70 human specimens between weeks 7 and 17 of development were studied by optical microscopy (25 embryos and 45 fetuses). All specimens were obtained from collections of the Institute of Embryology of the Complutense University of Madrid and the Department of Morphological Sciences of the University of Granada. Three phases in the development of the TMJ were identified. The first is the blastematic stage (weeks 7-8 of development), which corresponds with the onset of the organization of the condyle and the articular disc and capsule. During week 8 intramembranous ossification of the temporal squamous bone begins. The second stage is the cavitation stage (weeks 9-11 of development), corresponding to the initial formation of the inferior joint cavity (week 9) and the start condylar chondrogenesis. Week 11 marks the initiation of organization of the superior joint cavity. And the third stage is the maturation stage (after week 12 of development). This work establishes three phases in TMJ development: 1) the blastematic stage (weeks 7-8 of development); 2) the cavitation stage (weeks 9-11 of development); and 3) the maturation stage (after week 12 of development). This study identifies the critical period of TMJ morphogenesis as occurring between weeks 7 and 11 of development.

Background: The aim of this work is to clarify the aspects which are at present most controversial about the development of the anterior segments of Meckel's cartilage, such as the role of and determina- tion of the area that is incorporated in the development of the human mandible. Methods: Light microscope studies were done on 25 embryos and human fetuses from the collection of the Institute of Embryology at the University Complutense of Madrid and the Department of Morphological Science from the University of Granada. Specimen length was between 18 and 125 mm crown-rump. Results: During the embryonic period, Meckel's cartilages were placed in the midline of the mandibular arch but fusion was not observed between them. Ossification of Meckel's cartilage begins at the end of the embryonic period and is completed in the fetal period and the portion that participates in mandibular formation is determined. This segment ex- tends from the mental foramen to near the midline of the mandible. In this region, on the dorsal surface of the symphysis, cartilaginous nodules that originate from Meckel's cartilage are isolated. Conclusions: The ventral portions of Meckel's cartilage do not fuse in the midline of the mandibular arch. These present endo- and perichondral ossification and the section from the mental foramen to near the midline (mandibular symphysis) participates in mandibular formation. The ven- tral ends of Meckel's cartilage, i.e., the ends nearest the midline, do not ossify and remain isolated on the dorsal surface of the fetal mandibular symphysis. Anat. Rec. 249:249-254, 1997. r 1997 Wiley-Liss, Inc.

Background: Many studies have been published on the development of the human knee joint, but different investigators disagree on its morphogenetic time table. Most discrepancies center on the cavita- tion of the knee joint and the participation of the superior tibiofibular joint in the joint knee system. Methods:We summarize our observations of the development of the knee joint in 50 serially sectioned human embryonic and fetal lower limbs (26 embryos and 24 fetuses). Results: The epiphysis of the femur and tibia become condryfied from O'Rahilly stage 18, and ossification begins during the 13th week of development. The patella appears as a dense blastema during O'Rahilly stage 19, becomes condryfied during O'Rahilly stage 22, and begins its ossification during the 14th week of development. The knee joint cavity appears during O'Rahilly stage 22, initially as the femoropatellar joint. This process begins at the periphery of the articular interzone. The superior tibiofibular joint communicates with the lateral meniscotibial joint between 10 and 11 weeks of development and becomes separated from the 13 week on. The menisci arise from the eccentric portions of the articular interzone during O'Rahilly stage 22; however, until week 9 of development, they are not easily distinguishable. Conclusions: We establish the morphogenetic time table of the human knee joint. Anat. Rec. 248:269-278, 1997. r 1997 Wiley-Liss, Inc.

Background: Many studies have been published on the development of the human knee joint, but scant attention has been given to the development of the knee joint ligaments. The only elements that have received much attention are the cruciate ligaments and their relationships with the synovial membrane. Methods: We summarize our observations on the development of the knee joint ligaments in 50 serially sectioned human embryonic and fetal lower limbs (26 embryos and 24 fetuses). Results: The patellar ligament begins to form in O'Rahilly stage 20, with the muscle fibers of the quadriceps muscle being attached inferiorly to the tibial tuberosity. The cruciate ligaments (beginning with the posterior) arise from the articular interzone in O'Rahilly stage 21. Subsequently, with the organization of the Wrisberg's meniscofemoral ligament, in week 10 of development, the cruciate ligament system is completed. The lateral collateral ligament begins to form in O'Rahilly stage 23, and from its first appearance it is independent of the knee joint capsule. At this time, development of the tendon of the popliteus muscle begins. The medial collateral ligament begins to develop in week 9 of development as a condensation of the joint capsule. Two weeks later, the intra-articular pad of fat begins to form from mesenchymal tissue below the patella and between the cruciate and the patellar ligaments. With the organization of the suprapatellar bursa in week 14 of development, knee joint development is complete. Conclusions: The morphogenetic time table of the knee joint ligaments was established. Anat. Rec. 248:259-268, 1997. © 1997 Wiley-Liss, Inc.

Several studies have focused on the cartilaginous, articular, and ligamentous development of the craniovertebral joint (CVJ), but there are no unifying criteria regarding the origin and morphogenetic timetable of the structures that make up the CVJ. In our study, serial sections of 53 human embryonic (n = 27) and fetal (n = 26) specimens from O'Rahilly stages 17-23 and 9-13 weeks, respectively, have been analyzed. Our results demonstrate that the chondrification of the pars basioccipitalis and exoccipitalis becomes observable at stage 19, and all future bones in the CVJ are in their cartilaginous form except for the future odontoid process. In addition, two chondrification centers appear for the body of the axis. From stage 21, the apical, alar, and transverse atlantal ligaments begin to acquire a ligamentous structure and the odontoid process initiates its chondrogenic phase. Stage 22 witnesses the first signs of the articular cavities of the atlanto-occipital joint, and by stage 23 all joints have cavities except for the transverse-odontoid joint, which will wait until week 9. In week 10, the ossification of the basilar part of the occipital bone begins, followed by the rest of the structures except for the odontoid process, which will start at week 13, thus completing the osteogenesis of all bones in the CVJ. The results of this study could help in establishing the anatomical basis of the normally functioning CVJ and for detecting its related pathologies, abnormalities, and malformations.

Background Many studies have been published on the development of the human wrist joint, but scant attention has been given to the development of the wrist joint ligaments. Moreover, traditional description of wrist anatomy usually depict only the superficial capsular fibers of the wrist joint. The only ligamentous structure to receive much attention is the articular disc of the wrist joint, which has been described as a fibro-cartilaginous structure extending from the medial edge of the lower end of the radius to the ulnar styloid process. Methods In the present report, we synthesize our observations in the wrist joint ligaments in 35 serially sectioned human embryonic and fetal hands (16 embryos and 19 fetuses). Results The interosseous intercarpal ligaments are organized from the mesenchyme, which, until O'Rahilly's stage 23, fills the intercarpal spaces. These ligaments are not individually distinguishable until the 9th week of development. The collateral ligaments begin to form in O'Rahilly's stage 22 and are completely formed by the end of week 10. The palmar radiocarpal and ulnocarpal ligaments (beginning with the palmar radiocarpal ligament) begin to form in O'Rahilly's stage 23 and are fully developed by the end of week 10. At this time, development of the dorsal radiocarpal ligament begins; this process is completed by the end of week 13. The articular disc which is initially formed of a single element, first appears in O'Rahilly's stage 23 and its organization is completed at week 10 of development. Conclusions We establish the morphogenetic time-table of the wrist joint ligaments. Our descriptive findings may help explain carpal motion and the origin of wrist injuries. © 1996 Wiley-Liss, Inc.

Numerous experiments have yielded contradictory results on the harmful action of magnetic fields on embryonic development. Pulsed magnetic fields appear to be able to delay normal development of embryos. In the present study, fertilized Gallus domesticus eggs were exposed during incubation to pulsed magnetic fields (harmonic signals of 10 µT for 1 second with silences of 0.5 seconds) of 50 or 100 Hz frequency. Embryos extracted at 45 h of exposure to fields of 50 Hz or 100 Hz frequency had significantly (p0.05) fewer somite pairs compared with controls of the same age. At 15 days of incubation, only embryos exposed to a 10 µT- 50 Hz field had a significantly (p0.05) higher somatic weight. At 21 days of incubation, a significantly lower somatic weight (p0.01) and development stage (p0.05) was found in embryos exposed to a 10 µT-100 Hz field than in controls, while a lower development stage (p0.05) alone was observed in those exposed to a 10 µT-50 Hz field. In addition, animals showed higher expression of the neural marker NSE (neural specific enolase) after 21 days of development as determined by immunohistochemistry, with very low expression of glycosaminoglycans identified by alcyan blue staining. These results suggest that pulsed magnetic fields may be able to hinder normal embryonic development in vivo and to alter normal neural function, at least at the intensities and frequencies analyzed in the present study.

The beneficial effects of atorvastatin are based on both cholesterol-dependent and independent mechanisms. The latter probably include the ability of the estatin to enhance the expression of endothelial nitric oxide synthase (eNOS) and to cause a vasodilatation. In turn, the antioxidant and anti-inflammatory actions of melatonin are related to its vascular protection. In the present study, we investigated the efficacy of the combination of melatonin plus atorvastatin against endothelial cell damage induced by inflammation and oxidative stress injury. Human umbilical vein endothelial cells (HUVEC) were cultured with bacterial lipopolysaccharide (LPS) in the presence or absence of melatonin and/or atorvastatin. LPS inhibited eNOS mRNA and protein expression, which was reversed by atorvastatin and, to a lesser extent, by melatonin. Together, melatonin + atorvastatin induced higher eNOS protein expression than either compound alone. Melatonin, but not atorvastatin, reduced free radical generation, lipid peroxidation, and interleukin-6 levels induced by LPS. In the presence of atorvastatin, the effects of melatonin were maintained or even improved. These data suggest that melatonin improves the beneficial effects of atorvastatin and reduces its side effects in endothelial cells during inflammation and under conditions of oxidative stress.

Smoothelin is a cytoskeletal protein of differentiated smooth muscle cells with contractile capacity, distinguishing it from other smooth muscle proteins, such as smooth muscle actin (SMA).To evaluate the expression of smoothelin and SMA in the skin in order to establish specific localizations of smoothelin in smooth muscle cells with high contractile capacity and in the epithelial component of cutaneous adnexal structures.Immunohistochemical analysis (smoothelin and SMA) was performed in 18 patients with normal skin.SMA was expressed by the vascular structures of superficial, deep, intermediate and adventitial plexuses, whereas smoothelin was specifically expressed in the cytoplasm of smooth muscle cells of the deepest vascular plexus and in no other plexus of the dermis. The hair erector muscle showed intense expression of smoothelin and SMA. Cells with nuclear expression of smoothelin and cytoplasmic expression of SMA were observed in the outer root sheath of the inferior portion of the hair follicles and intense cytoplasmic expression in cells of the dermal sheath to SMA.We report the first study of smoothelin expression in normal skin, which differentiates the superficial vascular plexus from the deep. The deep plexus comprises vessels with high contractile capacity, which is important for understanding dermal hemodynamics in normal skin and pathological processes. We suggest that the function of smoothelin in the outer root sheath may be to enhance the function of SMA, which has been related to mechanical stress. Smoothelin has not been studied in cutaneous pathology; however we believe it may be a marker specific for the diagnosis of leiomyomas and leiomyosarcomas of the skin. Also, smoothelin could differentiate arteriovenous malformations of cavernous hemangioma of the skin.

A correlation was sought between the organization of the dental crest and the ossification of the corpus mandibulae in 14 human embryos and 13 human fetuses. The different types of ossification between the corpus and the ramus mandibulae suggest that the cartilago mandibularis (meckeliensis) guides the formation of the mandibula, while the dental crest acts as a coorganizer. In the area of the foramen mentale, the lamina dentalis begins to invaginate (to give rise to the dental crest), and at this level intramembranous ossification of the corpus mandibulae commences. These findings, together with the presence of the cartilago mandibularis before the appearance of the dental crest, and the fact that the former is seen along the entire length of the mandibula (from the symphysis mandibulae to the capsula otica), support the hypothesis that the dental crest, rather than the cartilago mandibularis, acts as the coorganizer in the corpus mandibulae. © 1993 Wiley-Liss, Inc.

This study was performed on 50 human embryos and fetuses between 7 and 17 weeks of development. Reichert's cartilage is formed in the second pharyngeal arch in two segments. The longer cranial or styloid segment is continuous with the otic capsule; its inferior end is angulated and is situated very close to the oropharynx. The smaller caudal segment is in contact with the body and greater horn of the hyoid cartilaginous structure. No cartilage forms between these segments. The persistent angulation of the inferior end of the cranial or styloid segment of Reichert's cartilage and its important neurovascular relationships may help explain the symptomatology of Eagle's syndrome.

Retinoic acid (RA), the active metabolite of vitamin A, plays a significant role in regulating cardiac form and function throughout the life of the organism. Both cardiac morphogenesis and myocardial differentiation are affected by alterations in RA homeostasis. In order to test the effect of all-trans RA and 13-cis RA on cardiomyocyte differentiation, we studied the level and the subcellular compartmentalization of α-tropomyosin and troponin-T proteins in cultures of chick embryo cardiomyocytes obtained from Hamburger and Hamilton’s (HH) stage 22, 32 and 40 embryos. The retinoids increased the levels of α-tropomyosin and troponin-T in the cytoplasmic and cytoskeletal fractions of cells at all three stages of development. The greatest increases in α-tropomyosin occurred in the cytoplasmic fraction in HH22 cells cultured for 24 h with all-trans RA or 13-cis RA, whereas the greatest increases in troponin-T were found in the cytoplasmic fraction of HH32 cells exposed to retinoids for 24 h. In cultures treated for 48 h with retinoids, the levels of α-tropomyosin and troponin-T showed significant increases in the cytoplasmic compartment of cells treated in HH32-with respect to the control values. These findings are further evidence that RA plays a modulating role in the formation and reorganization of sarcomeric proteins during the process of cardiomyocyte maturation.

Background The adrenal chromaffin cells synthesize, store and secrete a complex mixture containing amines, structural proteins, enzymes, and neurohormonal polypeptides. Most of the studies dealing with the development of the avian sympathoadrenal system have been based on antibodies recognizing signal molecules like HNK-1, NC-1, and N-CAM. Methods The development of the chick sympathoadrenal system was studied from 3½ to 21 days of incubation, both morphologically and immunocytochemically, using antibodies to 17 separate antigens, including antibodies to pan-neuroendocrine markers, catecholamine synthesizing enzymes, proprotein-processing enzymes, and neuropeptides. Results Some of the antigens studied were heavily expressed from the first days of development, e.g., chromogranin-A, chromogranin-B, Go protein-α subunit, tyrosine hydroxylase, and galanin, while for others a strong heterogeneity both in number of immunoreactive cells and intensity of immunostaining was recorded at the different stages, e.g., dopamine-β-hydroxylase, 7B2 protein, proprotein convertase 2, somatostatin, met-enkephalin, secretogranin II, proprotein convertase 3, neuropeptide Y, phenyl-N-methyl transferase, and neuron-specific enolase. The first immunoreactivities to appear at day 3½ were those for HNK-1, tyrosine hydroxylase, chromogranin-A, and chromogranin-B. Except for HNK-1, immunoreactivity for all the remaining antigens showed a steady increase up to the hatching. Conclusions Three expression patterns were found, in the developmental adrenal gland: defining early permanent markers (chromogranin-A, chromogranin-B, Go protein-α subunit, tyrosine hydroxylase, and galanin), others that show a progressively increased expression until the day 10 of development (dopamine-β-hydroxylase, 7B2 protein, proprotein convertase 2, somatostatin, met-enkephalin), and late-appearing antigens (secretogranin II, proprotein convertase 3, neuropeptide Y, phenyl-N-methyl transferase, and neuron-specific enolase). © 1996 Wiley-Liss, Inc.