Endoscopic Endonasal Approach in the Management of Rathke’s Cleft Cysts

Objective

Rathke’s cleft cysts (RCCs) are quite uncommon sellar lesions that can extend or even arise in the suprasellar area. The purpose of this study is to evaluate the effectiveness of both standard and extended endoscopic endonasal approaches in the management of different located RCCs.

Methods

We retrospectively analyzed a series of 29 patients (9 males, 20 females) complaining of a RCC, who underwent a standard or an extended endoscopic transsphenoidal approach at the Division of Neurosurgery, Department of Neurosciences and Reproductive and Odontostomatological Sciences, of the Università degli Studi di Napoli "Federico II”. Data regarding patients’ demographics, clinical evaluation, cyst characteristics, surgical treatments, complications and outcomes were extracted from our electronic database (Filemaker Pro 11, File Maker Inc., Santa Clara, California, USA).

Results

A standard transsphenoidal approach was used in 19 cases, while the extended variation of the approach in 10 cases (5 purely suprasellar and 5 intra-suprasellar RCC). Cysts contents was fully drained in all the 29 cases, whilst a gross total removal, that accounts on the complete cyst wall removal, was achieved in an overall 55,1% of patients (16/29), specifically 36,8% (7/19) that received standard approach and 90% (9/10) of those that underwent to extended approach. We reported a 56.2% of recovery from headache, 38.5% of complete recovery and 53.8% of improvement from visual field defect and an overall 46.7% of improvement of the endocrine functions. Postoperative permanent DI rate was 10.3%, overall post-operative CSF leak rate 6.9%; recurrence/regrowth occurred in 4 patients (4/29, 13.8%), but only one required a second surgery.

Conclusion

The endoscopic transsphenoidal approach for the removal of a symptomatic RCC offers several advantages in terms of visualization of the surgical field during both the exposure and removal of the lesion. The “extended” variation of the endoscopic approach provides a direct access to the supradiaphragmatic space, allowing adequate view and room for the safe removal of selected supradiaphragmatic RCCs, regardless of the sellar size (even a not enlarged sella), and provides a higher likelihood of preserving normal pituitary tissue and functions.     

Theory of Mind and Emotional Functioning in Fibromyalgia Syndrome: An Investigation of the Relationship between Social Cognition and Executive Function

Background

Fibromyalgia (FM) is a syndrome primarily characterised by chronic, widespread musculoskeletal pain. In the aetiology of this syndrome a crucial role is played by complex interactions among biological, genetic, psychological, and socio-cultural factors. Recently, researchers have started to explore emotional functioning in FM, with their attention focused on alexithymia, a personality construct that affects the regulation of a person’s own emotions. On the other hand, the detection and experience of emotional signals from other people have only been sparsely investigated in FM syndrome and no studies have investigated the ability to represent other people’s mental states (i.e. Theory of Mind, ToM) in these patients. Here we present the first study investigating a large set of social-cognitive abilities, and the possible relationships between these abilities and the performance on executive-function tasks, in a homogenous sample of patients with FM.

Methodology

Forty women with FM and forty-one healthy women matched for education and age were involved in the study. Social cognition was assessed with a set of validated experimental tasks. Measures of executive function were used to test the correlations between this dimension and the social-cognitive profile of patients with FM. Relationships between social-cognitive abilities and demographic, clinical and psychological variables were also investigated.

Principal Findings

Patients with FM have impairments both in the regulation of their own affect and in the recognition of other’s emotions, as well as in representing other people’s mental states. No significant correlations were found between social cognition tasks and the subcomponents of the executive function that were analysed.

Conclusions

The results show the presence of several impairments in social cognition skills in patients with FM, which are largely independent of both executive function deficits and symptoms of psychological distress. The impairments reported highlight the importance of adequately assessing ToM and emotional functioning in clinical practice.     

Flexor tendon and synovial gliding during simultaneous and single digit flexion in idiopathic carpal tunnel syndrome

The characteristic pathological finding in carpal tunnel syndrome (CTS) is non-inflammatory fibrosis of the subsynovial connective tissue (SSCT), which lies between the flexor tendons and the visceral synovium (VS). How this fibrosis might affect tendon function is unknown. To better understand the normal function of the SSCT, the relative motion of the middle finger flexor digitorum superficialis (FDS III) tendon and VS was observed during finger flexion in patients with CTS and cadavers with a history of CTS and compared to normal cadavers. A digital camcorder was used to monitor the gliding motion of the FDS III tendon and SSCT in eight patients with idiopathic CTS undergoing carpal tunnel release surgery (CTR), in eight cadavers with an antemortem history of CTS and compared these with eight cadaver controls. There were no significant differences noted in the total movement of the SSCT relative to the FDS III. However, the pattern of SSCT movement relative to the FDS III in the CTS patients and cadavers with an antemortem history of CTS differed from the controls in one of two patterns, reflecting either increased SSCT adherence to FDS III or increased SSCT dissociation from FDS III. In CTS, the gliding characteristics of the SSCT are qualitatively altered. These changes may be the result of increased fibrosis within the SSCT, which in some cases has ruptured, resulting in SSCT-tendon dissociation. Similar changes are also identified postmortem in the CTS patient.     

Characterization of methicillin resistant Staphylococcus aureus (MRSA) isolated at the Policlinico Hospital of Bari (Italy)

Methicillin resistant Staphylococcus aureus (MRSA) is an emerging problem. We studied 71 MRSA strains for the presence of mecA gene by PCR, for the enterotoxins production and susceptibility to antimicrobials. In addition, the suitability of Random Amplified Polymorphic DNA analysis (RAPD) and Hypervariable Region (HVR)--PCR as molecular tools for typing MRSA was also tested. All the 71 strains previously found MRSA with conventional methods, presented the gene mec A. By molecular typing five distinct amplicons were found. MRSA with two DRUS were the most common type. RAPD analysis clustered MRSA in 8 groups, three of which were the most common. 26.8% of MRSA produce enterotoxins with a prevalence of type A. MRSA exhibited resistance to all quinolones tested and to gentamycin. Our data suggest that a typing method based on RAPD combined with HVR-PCR may be useful to compare MRSA isolated in a hospital environment, whereas PFGE may be used for further analysis.     

Reproducible volar partial lacerations in flexor tendons: a new device for biomechanical studies

A device was designed to create clinically relevant, precise partial flexor digitorum profundus tendon lacerations for in vitro studies but can be adapted for in vivo studies. This caliper-based system utilizes a direct measurement of the tendon height and assumes an elliptical cross section to select the depth of the cut. The accuracy was tested on 60 cuts on 12 human tendons lacerated to an expected 50% or 75% of their cross-sectional area, based on the assumption that the cross-section was elliptical in shape. The cuts were made in portions of the tendon that varied in cross-sectional shape and size. The cut surface of the laceration was colored with Methylene blue and then the laceration was completed. The tendon cross-section was digitally imaged and the respective areas of the stained and unstained regions were evaluated using image-processing software. The mean lacerated areas were 52% (SD 5%) and 73% (SD 6%) for targeted lacerations of 50% and 75%, respectively. The device thus appears to be accurate within an acceptable 5% margin of error from the expected area, and adaptable to intra- and inter-tendinous size variations.     

Characterization of the Endocannabinoid System in Human Neuronal Cells and Proteomic Analysis of Anandamide-induced Apoptosis

Anandamide (AEA) is an endogenous agonist of type 1 cannabinoid receptors (CB1R) that, along with metabolic enzymes of AEA and congeners, compose the “endocannabinoid system.” Here we report the biochemical, morphological, and functional characterization of the endocannabinoid system in human neuroblastoma SH-SY5Y cells that are an experimental model for neuronal cell damage and death, as well as for major human neurodegenerative disorders. We also show that AEA dose-dependently induced apoptosis of SH-SY5Y cells. Through proteomic analysis, we further demonstrate that AEA-induced apoptosis was paralleled by an ∼3 to ∼5-fold up-regulation or down-regulation of five genes; IgG heavy chain-binding protein, stress-induced phosphoprotein-1, and triose-phosphate isomerase-1, which were up-regulated, are known to act as anti-apoptotic agents; actin-related protein 2/3 complex subunit 5 and peptidylprolyl isomerase-like protein 3 isoform PPIL3b were down-regulated, and the first is required for actin network formation whereas the second is still function-orphan. Interestingly, only the effect of AEA on BiP was reversed by the CB1R antagonist SR141716, in SH-SY5Y cells as well as in human neuroblastoma LAN-5 cells (that express a functional CB1R) but not in SK-NBE cells (which do not express CB1R). Silencing or overexpression of BiP increased or reduced, respectively, AEA-induced apoptosis of SH-SY5Y cells. In addition, the expression of BiP and of the BiP-related apoptotic markers p53 and PUMA was increased by AEA through a CB1R-dependent pathway that engages p38 and p42/44 mitogen-activated protein kinases. Consistently, this effect of AEA was minimized by SR141716. In conclusion, we identified BiP as a key protein in neuronal apoptosis induced by AEA.Endocannabinoids bind to and activate both type 1 (CB1R)⁴ and type 2 (CB2R) cannabinoid receptors and are widely recognized as important regulators of central and peripheral functions (1–3). The most studied endocannabinoids are anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) (1, 3). AEA, unlike 2-AG, binds to and activates also transient receptor potential vanilloid 1 (TRPV1), thus being considered a true “endovanilloid” (4).The “endocannabinoid system (ECS)” includes the receptors, their ligands AEA and 2-AG, and the enzymes that synthesize (N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD) and diacylglycerol lipase (DAGL)) or degrade (fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL)) AEA and 2-AG, respectively (1–3). On the other hand, there is still controversy about the identity and even the existence of purported “endocannabinoid transporters” that have not yet been cloned, isolated, or characterized (5). A growing interest is concerned with the ability of AEA to induce apoptosis in neuronal and non-neuronal cells (for comprehensive reviews see Refs. 6–9). Such a pro-apoptotic activity of AEA appears to be mediated by divergent pathways, each potentiated, reduced, or unaffected by cannabinoid or TRPV1 receptors (6–9). They can also be dependent on membrane cholesterol content (10, 11), generation of reactive oxygen species (12, 13), or even release of ethanolamine from AEA catalyzed by FAAH (14). In this context, it should be stressed that data on ECS and AEA-induced apoptosis in human neuronal cells are still very scant. Furthermore, a proteomic analysis of AEA-induced apoptosis has never been performed, leaving open the question of which proteins (if any) might be modulated at the level of expression upon induction of programmed cell death by this endocannabinoid. On this basis, we sought to characterize through functional and immunochemical assays and confocal microscopy the ECS components in human neuroblastoma SH-SY5Y cells. In addition, we performed a proteomic analysis of AEA-induced apoptosis in these cells that identified five proteins whose expression was modified. Among these proteins, one (BiP/GRP78) was shown to be modulated by AEA in a CB1R-dependent manner, in parallel with apoptosis. Through silencing and overexpression experiments, it was found to be a key player in the death program.     

Changes in postural sway and its fractions in conditions of postural instability

We investigated changes in postural sway and its fractions associated with manipulations of the dimensions of the support area. Nine healthy adults stood as quietly as possible, with their eyes open, on a force plate as well as on 5 boards with reduced support area. The center of pressure (COP) trajectory was computed and decomposed into rambling (Rm) and trembling (Tr) trajectories. Sway components were quantified using RMS (root mean square) value, average velocity, and sway area. During standing on the force plate, the RMS was larger for the anterior-posterior (AP) sway components than for the mediolateral (ML) components. During standing on boards with reduced support area, sway increased in both directions. The increase was more pronounced when standing on boards with a smaller support area. Changes in the larger dimension of the support area also affected sway, but not as much as changes in the smaller dimension. ML instability had larger effects on indices of sway compared to AP instability. The average velocity of Rm was larger while the average velocity of Tr was smaller in the AP direction vs. the ML direction. The findings can be interpreted within the hypothesis of an active search function of postural sway. During standing on boards with reduced support area, increased sway may by itself lead to loss of balance. The findings also corroborate the hypothesis of Duarte and Zatsiorsky that Rm and Tr reveal different postural control mechanisms.     

Reflex sympathetic dystrophy syndrome: consensus report of an ad hoc committee of the American Association for Hand Surgery on the definition of reflex sympathetic dystrophy syndrome

This report proposes that reflex sympathetic dystrophy be defined as a pain syndrome in which the pain is accompanied by loss of function and evidence of autonomic dysfunction. In the clinical setting, this diagnosis is usually associated with other anatomic and psychological diagnoses and may be associated with a variety of systemic illnesses and medicolegal factors. All components should be assessed before a treatment plan is established. Priorities should go to emergency care, acute injuries, and systemic illness, psychiatric problems, and chronic anatomic problems, in that order. Early, accurate diagnosis improves prognosis.     

BOLA‐DRB3 gene polymorphisms influence bovine leukaemia virus infection levels in Holstein and Holstein × Jersey crossbreed dairy cattle

Bovine leukemia virus (BLV) infections, causing persistent lymphocytosis and lethal lymphosarcoma in cattle, have reached high endemicity on dairy farms. We observed extensive inter‐individual variation in the level of infection (LI) by assessing differences in proviral load in peripheral blood. This phenotypic variation appears to be determined by host genetics variants, especially those located in the BoLA‐DRB3 MHCII molecule. We performed an association study using sequencing‐based typed BOLA‐DRB3 alleles from over 800 Holstein and Holstein × Jersey cows considering LI in vivo and accounting for filial relationships. The DBR3*0902 allele was associated with a low level of infection (LLI) (<1% of circulating infected B‐cells), whereas the DRB3*1001 and DRB3*1201 alleles were related to a high level of infection (HLI). We found evidence that 13 polymorphic positions located in the pockets of the peptide‐binding cleft of the BOLA‐DRB3 alleles were associated with LI. DRB3*0902 had unique haplotypes for each of the pockets: Ser¹³‐Glu⁷⁰‐Arg⁷¹‐Glu⁷⁴ (pocket 4), Ser¹¹‐Ser³⁰ (pocket 6), Glu²⁸‐Trp⁶¹‐Arg⁷¹ (pocket 7) and Asn³⁷‐Asp⁵⁷ (pocket 9), and all of them were significantly associated with LLI. Conversely, Lys¹³‐Arg⁷⁰‐Ala⁷¹‐Ala⁷⁴ and Ser¹³‐Arg⁷⁰‐Ala⁷¹‐Ala⁷⁴, corresponding to the DRB3*1001 and *1201 alleles respectively, were associated with HLI. We showed that the specific amino acid pattern in the DRB3*0902 peptide‐binding cleft may be related to the set point of a very low proviral load level in adult cows. Moreover, we identified two BOLA‐DRB3 alleles associated with a HLI, which is compatible with a highly contagious profile.