The effect of a combined rehabilitation program on the temporomandibular joint in systemic sclerosis evaluated by ultrasound exam.

PURPOSE: Temporomandibular joint (TMJ) involvement is frequent in Systemic Sclerosis (SSc). Dysfunction and X-ray changes of TMJ were described only in few observational studies. Treatment as well has been seldom considered. Aim of the present study was to evaluate the effects on TMJ of two specifically designed physiotherapy protocols. METHODS: The study group included 26 SSc outpatients (22 females and 4 males with mean age ± SD 59.08 ± 10.31 years). Thirteen patients were randomly assigned to a treatment (protocol 1) including home exercises for TMJ and thirteen to a treatment (protocol 2) including home exercises and a combined procedure. The rehabilitation effects on the TMJ were evaluated by ultrasound examination (UE) in static and dynamic phases. UE was performed in all patients before and at the end of the treatment and after a follow up (8 weeks). RESULTS: Both rehabilitation protocols induced a significant improvement (protocol 1: p < 0.01 and protocol 2: p < 0.005) of mouth opening with a long-lasting effect. Protocol 2 was more effective than protocol 1. A significant increase of bilateral condyle-head temporal bone distance was detected by UE at the end of both treatments. It was maintained at follow-up in patients treated with Protocol 2. CONCLUSIONS: The present investigation shows that a rehabilitation program characterized by home exercises with a combined procedure is useful to recover the function of TMJ. The data also show that UE is helpful in the evaluation of TMJ in SSc and in the assessment of the efficacy of the rehabilitation programs.

Algoritmo para el Manejo del Trauma Balístico Maxilofacial. Caso Clínico y Revisión de la Literatura

RESUMEN: El trauma maxilofacial por proyectil balístico corresponde a un escenario desafiante para los servicios de alta complejidad debido a su alta mortalidad y morbilidad, asociando gran costo en insumos, hospitalización y recursos, en contraste con la funcionalidad hacia una inserción laboral eficiente. En este sentido la cirugía de reconstrucción se relaciona con el daño presentado en los tejidos blandos y duros, siendo clasificada en etapa inmediata (reducción abierta y fijación con osteosintesis) y/o mediata en donde el uso de tutores externos continúa siendo una propuesta válida. Reporte de un paciente masculino de 38 años, que ingresa por trauma balístico maxilofacial con daño extenso en tejido blando y conminución en cuerpo de mandíbula, siendo tratado de manera mediata por estabilización de tutores externos y posterior reconstrucción con injerto autólogo no vascularizado; presentándose complicación intraoperatoria de comunicación de acceso extraoral con intraoral; cerrado con injerto loco regional de cuerpo adiposo de mejilla. Paciente presenta evolución favorable. Se realizó una revisión de literatura en relación al uso de cuerpo adiposo de mejilla en cirugía maxilofacial reconstructiva. El uso de tutores externos se presenta como una alternativa válida y favorable para traumatismos con daño extenso en tejido blando y duro. El uso de cuerpo adiposo de mejilla se reporta en variados usos en cirugía oral y maxilofacial, sin embargo, su uso como injerto locoregional para cierre de procesos que requieren ser injertados es escaso; planteándose como una propuesta en este reporte.

ABSTRACT: Ballistic projectile maxillofacial trauma corresponds to a challenging scenario for highly complex services due to high mortality and morbidity, associating high cost in supplies, hospitalization and resources, in contrast to the functionality towards efficient labor insertion. In this sense, reconstruction surgery is related to the damage presented in the soft and hard tissues, being classified in the immediate stage (open reduction and fixation with osteosynthesis) and / or mediate where the use of external tutors continues to be a valid proposal. Report of a 38-year-old male patient admitted for maxillofacial ballistic trauma with extensive soft tissue damage and comminution in the mandible body, being treated mediate by stabilization of external tutors and subsequent reconstruction with a non- autologous graft. vascularized; presenting intraoperative complication of communication between extraoral and intraoral access; closed with a locoregional flap of the adipose body of the cheek. The patient presents a favorable evolution. A literature review was carried out in relation to the use of the adipose body of the cheek in reconstructive maxillofacial surgery. The use of external tutors is presented as a valid and favorable alternative for trauma with extensive damage to soft and hard tissue. The use of the adipose body of the cheek is reported in various uses in oral and maxillofacial surgery, however, its use as a locoregional graft for closing processes that require grafting is scarce; it is presented as a proposal in this report.

[Pneumonectomy: an alternative to sleeve resection in lung cancer patients?]. / Pneumonektomie: Eine Alternative zur Manschettenresektion beim Lungenkarzinom?

Lung cancer is localized in the upper lobes in more than half of the cases. The risk of tumor infiltration of centrally located structures, such as bronchi and vessels are enhanced due to the anatomic topography. Pneumonectomy competes with sleeve resection for the surgical resection of centrally located tumors. The present review deals with the question if pneumonectomy should be considered as an alternative to sleeve resection for the treatment of lung cancer. Primary pneumonectomy does not provide any advantage even in advanced nodal disease. Extended lymph node dissection is not a contraindication for sleeve resections. Local recurrence rate is lower after sleeve resections despite the same radicality for both surgical treatment options. Mortality and morbidity rates are significantly lower for sleeve resections. Sleeve resections are associated with prolonged survival and better quality of life even in elderly patients.

Non-traumatic sphenoidal intradiploic arachnoid cyst as a cause of trigeminal neuralgia. A case report.

Non-traumatic intradiploic arachnoid cyst is a rare condition. We describe a young man with typical trigeminal neuralgia and intradiploic arachnoid cyst at the greater wing of the sphenoid. The patient was successfully treated with medical therapy. To our knowledge, this is the first case report of a possible correlation between trigeminal neuralgia and intraosseous arachnoid cyst. We describe the clinical case, the possible pathogenetic mechanism and briefly review the literature.

Efficacy of a tailored rehabilitation program for systemic sclerosis.

INTRODUCTION: Rehabilitation may contribute to the management of Systemic Sclerosis (SSc) dealing with disabilities due to skin and joint involvement. AIM: to evaluate the efficacy of a district specific and global rehabilitation program tailored for SSc patients. MATERIALS AND METHODS: 20 SSc patients were enrolled and randomly assigned to 2 groups. Interventional group (10 pts) was treated that included hand and face specific rehabilitation and at least a global rehabilitation technique such as hydrokinesytherapy or land-based program, also comprising respiratory exercises. Hand lymphatic drainage was added when necessary. Observational group (10 patients) was only provided with educational advices and medical information about SSc. Patients were evaluated at baseline (T0) and after the 9 weeks treatment period (T1). Interventional group was also assessed after a 9 weeks follow-up (T2). Patients were evaluated by SF-36, HAQ and a purpose-built-questionnaire for global health condition and with Hamis test, Duruöz scale, range of motion, water volumetric test, mouth opening and a purpose-built-questionnaire for hand and face involvement. RESULTS: At the end of the treatment, patients of interventional group improved in all the parameters evaluated. At follow-up, mouth mobility and functionality such as global health status was partially lost, only hand mobility and functionality parameters were maintained. No changes were observed in controls. CONCLUSION: The association and of district-specific and global rehabilitative techniques conceived and tailored for SSc patients improves disability, HRQoL, hand and face disability and functionality, with its effects partially maintained at the follow-up.

IGF-I induced rapid recruitment of integrin beta1 to lipid rafts is Caveolin-1 dependent.

Caveolin-1 (Cav-1) regulates both insulin like growth factor receptor (IGF-IR) and integrin beta1 function. However, the role of Cav-1 in IGF-IR/integrin beta1 cross talk remains to be established. In this study, we observed that IGF-I did not induce integrin beta1 internalization but its plasma membrane reorganization. In particular, we found a rapid and transient association between integrin beta1 and Cav-1 followed by the enrichment of integrin beta1 in lipid rafts. To determine the role of Cav-1 in this process, we transfected Hacat cells with small interfering RNA specific for Cav-1 (siRNA-Cav-1) and with a scrambled siRNA as control (siRNA-Ctr). Cav-1 down regulated Hacat cells were then stimulated with IGF-I and analyzed by immunofluorescence and flow cytometry. We found that Cav-1 silencing abolished the recruitment of integrin beta1 to lipid rafts in the presence of IGF-I. These data demonstrate that IGF-IR/integrin beta1 cross talk is followed by integrin beta1 lipid raft compartmentalization and that Cav-1 is required for this process.

Replication pattern of the pericentromeric region of chromosome 10q and expression of the RET protooncogene.

Regulation of the RET gene is highly specific during embryo development and is strictly tissue-specific. Control of transcription depends on mechanisms influenced by epigenetic processes, in particular, histone acetylation at regions flanking the 5' end of the gene. Since the RET gene is mapped in the pericentromeric region of the human chromosome 10, the implication of epigenetic processes is even more striking and worth to be investigated in an extended chromosomal tract. One experimental approach to study the chromatin status in relationship with gene transcription is to assess the replication timing, which we did by using fluorescent in situ hybridization in cells expressing or not expressing the RET gene. By using probes spanning a 700-kb genomic region from the RET locus toward the centromere, we found a relationship between RET expression and early replication. Different patterns were observed between cells naturally expressing RET and cells induced to expression of RET by treatment with sodium butyrate, an inhibitor of histone deacetylases. Three-dimensional analysis of the nuclear localization of fluorescent signals by confocal microscopy showed difference of localization between the RET probe and a probe for a housekeeping gene, G3PDH, located at 12p13.3, in cells that do not express RET, in accordance with previous data for other genes and chromosomal regions. However, RET-expressing cells showed a localization of signals which was not consistent with that expected for expressed genes.

Radicular compression by lumbar intraspinal epidural gas pseudocyst in association with lateral disc herniation. Role of the posterior longitudinal ligament.

Among unusual abnormalities of the lumbar spine reported since the introduction of Computed Tomography (CT), the presence of gas lucency in the spinal canal, known as vacuum phenomenon, is often demonstrated. On the contrary, epidural gas pseudocyst compressing a nerve root in patients with a lateral disc herniation has rarely been reported. We report a case of a 44-year-old man who experienced violent low back pain and monolateral sciatica, exacerbated by orthostatic position, one week before admission. A lumbosacral spine CT showed the presence of vacuum phenomenon associated with a degenerated disc material and a capsulated epidural gas collection with evidence of root compression. A microsurgical interlaminar approach was carried out and, before the posterior longitudinal ligament was entered, a spherical "bubble" compressing the nerve roots was observed. The capsulated pseudocyst was dissected out, peeled off and excised en bloc. A large part of the posterior longitudinal ligament and the lateral disc herniation were removed. Postoperatively the patient was completely free of symptoms. The mechanism of exacerbation of pain was probably due to the increased radicular compression in the upright posture and, besides the presence of a lateral disc herniation, could be related to a pneumatic squeezing of gas from the intervertebral space into the well capsulated sac by the solicitated L4-L5 motion segment. Histological study of the wall of the pseudocyst showed the presence of fibrous tissue identical to the ligament. We conclude that, in case of a lumbar disc herniation, it is recommended to perform a complete microdiscectomy and an accurate removal of the involved portion of posterior longitudinal ligament in order to prevent pseudocystic formations.

Identification of an import signal for, and the nuclear localization of, human lactoferrin.

Many different unique functions have been attributed to lactoferrin (Lf), including DNA and RNA binding, and transport into the nucleus, where Lf binds to specific sequences and activates transcription. A pentapeptide, Gly-Arg-Arg-Arg-Arg, corresponding to a region of the N-terminal portion of human Lf rich in basic amino acids, was synthesized and its intracellular localization was investigated. Peptide internalization was assayed using the rhodaminated form of the same molecule. This N-terminal peptide sequence is able to be internalized within less than 10 min at concentration as low as 1 microM, and its intracellular localization is nuclear, mainly nucleolar. Similar behaviour was observed using peptides composed of either all l or d amino acids, the last one being a retro-inverse peptide. The internalization process does not involve an endocytotic pathway, since no inhibition of the uptake was observed at 4 degrees C. The kinetics of peptide internalization was also evaluated. The internalization properties of such a short Lf pentapeptide have been assayed for its ability to transport peptide nucleic acids (PNAs) inside cells in order to improve their efficacy. The abundant transmembrane transport and nuclear localization of the proposed peptide, deriving from hLf and, for the first time, identified as a nuclear localization signal, could be used as an alternative strategy to tackle the unsolved problem of intracellular accumulation of antisense and antigene drugs and for the development of new pharmacological tools.

Extracellular processing of amphoterin generates a peptide active on erythroleukaemia cell differentiation.

The release of amphoterin by murine erythroleukaemia cells exposed to the chemical inducer hexamethylenebisacetamide represents an essential step for the process of their terminal differentiation. Once exported in the culture medium, amphoterin undergoes limited proteolysis, catalysed by a serine proteinase also secreted by stimulated cells. The isolated proteinase is responsible for degradation of amphoterin, with the production of a 10-amino-acid-residue fragment, specifically retaining the cell-differentiation-stimulating activity of the native protein molecule. This peptide does not express other properties of amphoterin, such as protein kinase C-stimulating activity or systemic toxicity. These findings define a selective mechanism accounting for extracellular amphoterin functional maturation.

Changes in intracellular calpastatin localization are mediated by reversible phosphorylation.

We have previously reported that, in neuroblastoma LAN-5 cells, calpastatin is in an aggregated state, close to the cell nucleus [de Tullio, Passalacqua, Averna, Salamino, Melloni and Pontremoli (1999) Biochem. J. 343, 467-472]. In the present paper, we demonstrate that aggregated calpastatin is predominantly in a phosphorylated state. An increase in intracellular free [Ca2+] induces both dephosphorylation of calpastatin, through the action of a phosphoprotein phosphatase, and its redistribution as a soluble inhibitor species. cAMP, but not PMA-induced phosphorylation, reverses calpastatin distribution favouring its aggregation. This intracellular reversible mechanism, regulating the level of cytosolic calpastatin, could be considered a strategy through which calpain can escape calpastatin inhibition, especially during earlier steps of its activation process.

Simulated microgravity induces alteration in the central nervous system.

To investigate whether the signs of neurophysiological impairment observed in flight may be traced back to cytomorphology, we undertook a ground-based study focusing upon the architecture of cultured glial cells under simulated microgravity obtained by three-dimensional clinorotation.

Immunocytochemical localization of serotonin in embryos, larvae and adults of the lancelet, Branchiostoma floridae.

Serotonin (5-hydroxytryptamine) is a biogenic amine distributed throughout the metazoans and has an old evolutionary history. It is involved as a developmental signal in the early morphogenesis of both invertebrates and vertebrates, whereas in adults it acts mainly as a neurotransmitter and gastrointestinal hormone. In vertebrates, serotonin regulates the morphogenesis of the central nervous system and the specification of serotonergic as well as dopaminergic neurons. The present study uses, as an experimental model, an invertebrate chordate, the lancelet Branchiostomafloridae, characterized by its remarkable homologies with vertebrates that allows the 'bauplan' of the probable ancestor of vertebrates to be outlined. In particular, the involvement of serotonin as a developmental signal in embryos and larvae, as well as a neurotransmitter and gastrointestinal hormone in adult specimens of Branchiostoma floridae, gives further support to a common origin of cephalocordates and vertebrates.

Human neuroblastoma cell differentiation requires protein kinase C-theta.

Neuroblastoma LAN-5 cells exposed to retinoic acid cease to multiply and extend neurite outgrowths acquiring a neuronal phenotype. We now report that protein kinase C-theta; (PKC-theta;) isozyme is involved in this differentiation process due to the following findings: (i) PKC-theta; is expressed by LAN-5 cells as a nuclear and perinuclear protein; (ii) cell stimulation with retinoic acid promotes in a large increase in the expression level of the kinase and its intracellular redistribution; and (iii) a PKC-theta; antisense oligonucleotide reduces at the same time the expression level of the kinase and the cell response to retinoic acid. Altogether these data are consistent with a specific role played by PKC-theta; in the differentiation program of neuronal cells.

Effect of recombinant human erythropoietin on cerebral ischemia following experimental subarachnoid hemorrhage.

Erythropoietin exerts a neuroprotective effect during cerebral ischemia. We investigated the effect of systemic administration of recombinant human erythropoietin in a rabbit model of subarachnoid hemorrhage-induced acute cerebral ischemia. The animals were divided into three groups: group 1, subarachnoid hemorrhage; group 2, subarachnoid hemorrhage plus placebo; group 3, subarachnoid hemorrhage plus recombinant human erythropoietin (each group, n=8). Experimental subarachnoid hemorrhage was produced by injecting autologous blood into the cisterna magna. Treatment with recombinant human erythropoietin and placebo was started 5 min after subarachnoid hemorrhage and was continued every 8 h for 24 h. Before the animals were killed, erythropoietin concentration was measured in the cerebrospinal fluid. The rabbits were killed 24 h after subarachnoid hemorrhage and ischemic brain injury was histologically evaluated. In group 3, the concentration of erythropoietin in the cerebrospinal fluid was significantly increased and a significant reduction in cortical necrotic neuron count was also observed. These findings may encourage the use of erythropoietin in the treatment of cerebral ischemia that often occurs in the early stage of subarachnoid hemorrhage.

Neuronal differentiation of PC12 cells involves changes in protein kinase C-theta distribution and molecular properties.

In this study we demonstrate that the rat pheochromocytoma PC12 cell line expresses the novel protein kinase C isozyme designated PKC-θ. The isozyme is almost completely localized in the nuclear compartment of proliferating cells. Following stimulation with the nerve growth factor, PKC-θ is redistributed into the cytoplasm and the outgrowing neurite processes, mostly as a cytoskeletal associated kinase. This event is accompanied by an eightfold increase in the expression level and by the appearance of specific modifications of PKC-θ molecule. Conversely, the kinase is down-regulated once cells reach the terminally differentiated state displaying a neuron-like phenotype. These data suggest a functional role for the kinase in the regulation of cytoskeletal modeling along the multistage differentiation process of PC12 cells.

Changes in intracellular localization of calpastatin during calpain activation.

Localization of the two main components of the Ca(2+)-dependent proteolytic system has been investigated in human neuroblastoma LAN-5 cells. Using a monoclonal antibody which recognizes the N-terminal calpastatin domain, it has been shown that this inhibitory protein is almost completely confined in two granule-like structures not surrounded by membranes. Similar calpastatin distribution has been found in other human and in murine cell types, indicating that aggregation of calpastatin is a general property and not an exclusive characteristic of neuronal-like cells. The existence of such calpastatin aggregates is confirmed by the kinetics of calpastatin-activity release during rat liver homogenization, which does not correspond to the rate of appearance of cytosolic proteins or to the disruption of membrane-surrounded organelles. Calpastatin distribution is affected by the intracellular increase in free Ca(2+), which results in calpastatin progressively becoming a soluble protein. However, calpain is distributed in the soluble cell fraction and, in activating conditions, partially accumulates on the plasma membrane. Similar behaviour has been observed in calpastatin localization in LAN-5 cells induced with retinoic acid, suggesting that the proteolytic system is activated during the differentiation process of these cells. The involvement of calpastatin in controlling calpain activity, rather than its activation process, and the utilization of changes in calpastatin localization as a marker of activation of the system is discussed.

Protein kinase C-theta is specifically activated in murine erythroleukaemia cells during mitosis.

Protein kinase C-theta is a member of the n-protein kinase C subfamily that in mitotic cells translocates to centrosomes and kinetochores. Although this kinase is expressed in comparable amounts in murine erythroleukaemia cells during the interphase or metaphase, when localized in the mitotic structures, it selectively phosphorylates a 66 kDa protein, also associated to chromosomes. Moreover, protein kinase C-theta immunoprecipitated from cells at the metaphase results four times more active in the absence of lipid cofactors as compared with the kinase obtained from cells in the interphase. This activation is accomplished by interaction of protein kinase C-theta with a protein factor which also promotes an increased autophosphorylation of the kinase. These findings indicate that in the mitotic phase of the cell cycle, protein kinase C-theta recognizes a protein factor which operates as a positive modulator of the kinase activity in the absence lipids.

Transsphenoidal microsurgical selective removal of multiple (triple) adenomas of the pituitary gland.

This is the first case of multiple (triple) pituitary micro-adenomas documented by magnetic resonance imaging (MRI) in a living patient and treated by a transsphenoidal microsurgical approach. The patient, a 37-year-old woman, complained of a long history of bifrontal headache, weight gain and oligomenorrhea. Physical examination revealed moderate hirsutism and a slight fat pad overlying the vertebrae. Routine laboratory studies and endocrinological biochemical investigations were normal. A gadolinium-enhanced MRI of the pituitary region revealed three intrapituitary micro-adenomas. A transsphenoidal microsurgical approach to the pituitary gland was carried out and micro-adenomas were completely removed one at a time. One year follow-up showed complete resolution of clinical symptoms and signs and normal biochemical parameters of pituitary function.