Gender-specific effects of capsiate supplementation on body weight and bone mineral density: a randomized, double-blind, placebo-controlled study in slightly overweight women.

INTRODUCTION: Overweight and obesity are highly prevalent conditions associated with premature morbidity and mortality worldwide. Capsiate, a nonpungent analogue of capsaicin, binds to TRP vanilloid 1 (TRPV1) receptor, which is involved in adipogenesis, and could be effective as a weight-lowering agent. METHODS: Eighteen slightly overweight women were enrolled in this randomized, double-blind, placebo-controlled study. Nine patients were included in the capsiate intervention group and received 9 mg/day of capsinoids and 9 patients received placebo for 8 weeks. All patients underwent weight and waist circumference assessment before and after treatment. Body composition and bone mineral density (BMD) were also detected by dual-energy X-ray absorptiometry (DXA). RESULTS: Fourteen patients completed the study. The treatment with capsiate or placebo for 8 weeks was not associated with significant changes in weight or waist circumference. After treatment, there was a significant improvement in BMD values measured at the spine in the capsiate group (1.158 vs 1.106 g/cm2, + 4.7%; p = 0.04), but not in the group treated with placebo. Similarly, the capsiate group showed a 9.1% increase (p = 0.05) in the adipose tissue and an 8.5% decrease in lean mass measured at the supraclavicular level, whereas these changes were not statistically significant in the placebo group. CONCLUSIONS: Treatment with capsiate for 8 weeks led to negligible changes in body weight in a small sample of slightly overweight women, but our findings suggest a potential effect of capsaicin on bone metabolism in humans.

Tetraplegia following parathyroidectomy in two long-term haemodialysis patients.

We report two cases of postoperative iatrogenic tetraparesis, which occurred in different hospitals after surgery for parathyroidectomy. Both patients were on long-term haemodialysis. The prolonged neck extension usually required by this procedure was probably the main factor involved in the genesis of the spinal cord injury. Spinal abnormalities associated with chronic renal failure may have made these patients more vulnerable. In our opinion, it is advisable to investigate thoroughly any sign of spinal stenosis in patients who undergo any procedure requiring significant neck extension, particularly if on long-term haemodialysis.

A case of epilepsia partialis continua of abdominal muscles after brain tumor surgery.

Epilepsia partialis continua (EPC) is a rare form of focal motor status epilepticus characterized by continuous muscular twitches or jerks involving a limited part of the body, usually facial region and distal limb. Although the cerebrovascular disease is known to be one of the most common causes of this condition, other reported cases with predominant abdominal involvement have different aetiologies, including, tumors, focal cortical dysplasia, and central nervous system infections. No cases of epilepsia partialis continua of the abdominal wall occurred after brain surgery have been previously reported. We describe the clinical, electrophysiological, and neuroimaging findings in an adult patient presenting with persistent unilateral abdominal myoclonus configuring an EPC as the evolution of a super-refractory hemibody convulsive status epilepticus, occurred after brain tumor surgery.

Infarct Volume Predicts Hospitalization Costs in Anterior Circulation Large-Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: Anterior circulation large-vessel occlusion stroke, one of the most devastating stroke subtypes, is associated with substantial economic burden. We aimed to identify predictors of increased acute care hospitalization costs associated with anterior circulation large-vessel occlusion stroke. MATERIALS AND METHODS: Comprehensive cost-tracking software was used to calculate acute care hospitalization costs for patients with anterior circulation large-vessel occlusion stroke admitted July 2012 to October 2014. Patient demographics and stroke characteristics were analyzed, including final infarct volume on follow-up neuroimaging. Predictors of hospitalization costs were determined using multivariable linear regression including subgroup cost analyses by treatment technique (endovascular, IV tPA-only, and no reperfusion therapy) and sensitivity analyses incorporating patients initially excluded due to early withdrawal of care. RESULTS: Three hundred forty-one patients (median age, 69 years; interquartile range, 57-80 years; median NIHSS score, 16; interquartile range, 13-21) were included in our primary analysis. Final infarct volume, parenchymal hematoma, baseline NIHSS score, ipsilateral carotid stenosis, age, and obstructive sleep apnea were significant predictors of acute care hospitalization costs. Final infarct volume alone accounted for 20.87% of the total cost variance. Additionally, final infarct volume was consistently the strongest predictor of increased cost in primary, subgroup, and sensitivity analyses. CONCLUSIONS: Final infarct volume was the strongest predictor of increased hospitalization costs in anterior circulation large-vessel occlusion stroke. Acute stroke therapies that reduce final infarct volume may not only improve clinical outcomes but may also prove cost-effective.

Intraoperative localization of subcortical brain lesions.

BACKGROUND: Some brain tumors may grow immediately beneath the cortical surface without distorting its appearance. Intraoperative image guidance promotes safe resection. We have developed MRI-based corticotopography (MRI-bct), to localize lesions during surgery, using simple, non-dedicated equipment, to match a three-dimensional reconstruction with the corresponding appearance of the brain cortex. METHODS: Forty-six patients underwent resection of subcortical brain lesions, aided by MRI-bct. The lesions had a maximum diameter less than 3 cm, were subcortical but no deeper than the floor of the nearest cerebral sulcus. Each patient had a volumetric MRI scan with and without contrast administration. Data sets were transferred to a laptop personal computer and processed using a rendering software. At operation, the three-dimensional model of the brain, including a surface overlay of the lesion, was matched to the exposed brain surface. After its exact relationship with the overlying sulcal pattern was defined, the lesion was localized and resected. In selected patients, the procedure was coupled with functional brain mapping. RESULTS: Data processing took from 10 to 15 min and could be done whenever convenient before operation. Surface matching between the surgical field and the reformatted MRI always required less than 5 min and was done near the operating table. In all patients, the lesion was identified at the first attempt, through a small corticotomy, regardless of the brain shift after dural opening. CONCLUSIONS: MRI-bct is a practical, time-saving neuronavigational aid ideal for localizing superficial lesions underlying the cerebral cortex because it unmistakably characterizes the adjacent sulcal anatomy.

Post-radiation intramedullary malignant peripheral nerve sheath tumor.

We report the intramedullary growth of a malignant peripheral nerve sheath tumour (MPNST). A 50year-old man developed a severe tetraparesis over a 4-month period. Following irradiation of a chronic tonsillitis during his childhood, the patient had later experienced a number of post-radiation diseases, including a laryngeal cancer that required permanent tracheotomy. Before admission, a magnetic resonance imaging (MRI) study had disclosed a C4-C5 intramedullary lesion. On admission to our Department, the patient had a nearly complete tetraparesis. At surgery, the lesion was exposed through a posterior midline myelotomy. A friable neoplasm, with no clear plane of cleavage, was found. The tumour was subtotally resected. Histological examination, which intraoperatively had not yielded a specific diagnosis, eventually revealed a MPNST, grade intermediate, with ultrastructural and immunohistochemical features consistent with a schwannian differentiation. No postoperative radiotherapy was undertaken. The patient died 9 months later from pneumonial complications. MPNSTs may develop within the spinal cord similarly to their benign schwannian counterpart. The reported sequence of events might support a possible relation between irradiation of the spinal cord and induction, followed by malignant transformation, of intramedullary schwannosis. This unique case must be added to the growing list of radiation-induced spinal cord tumours.

Hemilaminectomy for spinal meningioma: A case series of 20 patients with a focus on ventral- and ventrolateral lesions.

OBJECTIVE: To demonstrate the effectiveness and safety of hemilaminectomy in spinal-meningioma surgery, with special attention to ventral lesions. We also describe technical tips to enhance surgical-corridor width. PATIENTS AND METHODS: A total of 20 patients (14 female and 6 male) underwent hemilaminectomy for resection of a spinal meningioma between January 2005 and December 2015. Preoperative magnetic resonance imaging defined the tumor location (16 thoracic, 3 cervical, 1 lumbar) and the dural-attachment site (4 ventral, 11 ventrolateral, 3 lateral, 2 posterior). Pre- and postprocedural functional status was evaluated according to McCormick's classification. Intraoperative neurophysiological monitoring was employed in all patients. RESULTS: The unilateral approach allowed for complete resection (Simpson grade I-II resection) in 18 patients (90%), including tumors with a ventral dural attachment. In most patients (n=13), monosegmental hemilaminectomy was performed, a single patient required hemilaminectomy of 3 levels, while the remaining 6 patients underwent hemilaminectomy of 2 levels. No patients experienced either worsening of neurological status or procedure-related complications. All patients who had preoperative pain reported postoperative improvement. CONCLUSIONS: The goal of surgery for spinal tumors is to achieve gross tumor removal while minimizing morbidity. In our experience, hemilaminectomy is an effective surgical approach, even in patients with ventral- and ventrolateral spinal meningiomas. The procedure offers several advantages in terms of early patient mobilization and rehabilitation, management of postoperative pain, and preservation of spinal stability while achieving positive functional outcomes.

Porcine odorant-binding protein: structural stability and ligand affinities measured by fourier-transform infrared spectroscopy and fluorescence spectroscopy.

Infrared spectra show that the binding of the odorants 2-isobuthyl-3-methoxypyrazine (PYR) and 3,7-dimethyl-1-octanol (DMO) stabilises the tertiary structure of porcine OBP-I against thermal denaturation. The fluorescence emission spectrum of the single tryptophan shows a lambdamax at 337 nm, indicating that the residue is not directly exposed to the solvent. Tryptophan does not appear to be involved in the odorant binding process and it is not accessible to the fluorescence quenchers NaI, CsCl and acrylamide. The binding of the fluorescent dye 1-aminoanthracene (1-AMA), a strong ligand, does not modify the tryptophan fluorescence spectrum. In contrast, the lambdamax of 1-AMA bound to OBP-I is shifted from 537 to 481 nm, with a lambdamax intensity increase by a factor of 80. Bound 1-AMA is displaced by odorant molecules in competitive binding assays and can be employed in simple and rapid binding assay, avoiding the use of radioactive ligands. The Scatchard plot shows that 1-AMA binds to OBP-I with a dissociation constant of 1.3 microM and an equimolar stoichiometry.

Cerebral Whipple's disease as a cause of reversible dementia.

We describe a case of reversible dementia caused by Tropheryma whippelii (TW). Diagnosis was confirmed by a positive polymerase chain reaction for this pathogen both on serum and cerebrospinal fluid. Specific antibiotic therapy resulted in distinct clinical and neuroradiological improvement. Control polymerase chain reaction for T. whippelii on serum and cerebrospinal fluid was negative.

Spinal subarachnoid hematomas: our experience and literature review.

STUDY DESIGN: Spinal subarachnoid hematomas are unusual and difficult to diagnose and the outcome of treatment is influenced by the lesions that frequently accompany them. OBJECTIVES: To clarify the neuroradiological diagnostic aspects of spinal subarachnoid hematoma as well as the results of treatment. BACKGROUND: Only recently has subarachnoid hematoma been clearly distinguished from more common subarachnoid hemorrhage and its characteristics have still not been dealt with in detail. METHODS: A total of 69 cases (3 personal case, 66 published cases) were revised in terms of etiology, diagnostic imaging and the results of both surgical and conservative treatment. RESULTS: The most common causes of spinal subarachnoid hematoma are coagulopathies (either pharmacologically-induced or resulting from systemic diseases) (40.5%), lumbar puncture for diagnostic or anesthesiological purposes (44.9%) and traumatic injuries (15.9%): these factors may be present singly or variously combined. They may be spontaneous (17.3%) or, in rare cases, associated with aortic coarctation or degenerative vascular diseases. Overall mortality is 25.7%. In the 50 cases in whom long-term follow-up was possible, the outcome of treatment, which is almost exclusively always surgical, was good in 93.5% of 31 patients in whom neurological status on admission was satisfactory and in 15.8% of 19 cases with severe neurological deficits. CONCLUSIONS: MRI and CT are not usually diagnostic because they are not able to differentiate between a subarachnoid lesion and a subdural one. However, diagnosis may be possible when these investigations detect the CSF or the contrast medium surrounding the hematoma. Although the risks of producing spinal subarachnoid hematoma as a result of LP are remote, this is, in fact, the primary cause in patients with coagulopathies. The results of treatment depend on the patient's initial neurological condition, the severity of any concomitant pathologies, the position of the hematoma and the eventual association of a subdural hematoma.

Radiation injury involving the internal carotid artery. Report of two cases.

Radiation therapy is an uncommon cause of stenosis and occlusions of the cervical internal carotid artery (ICA). We describe two cases of cerebral ischemia due to ICA stenosis in patients irradiated for malignant tumors (lymphoma and breast cancer). The first patient, a 32-year-old man, presented with an episode of cerebral ischemia. Six years previously he had received irradiation therapy for a left laterocervical mass histologically diagnosed at biopsy as a Hodgkin's lymphoma. Cerebral angiography on entry revealed bilateral occlusion of the cervical ICA, with a 2-cm stump at the origin of the left ICA. Despite anti-platelet aggregation therapy the ischemic attacks persisted, necessitating a stumpectomy. After vascular-repair surgery the patient had no further ischemic symptoms. The second patient, a 42-year-old woman, began to experience the sudden onset of pain in the right arm and left hemiparesis five years after surgery plus irradiation (4500 rad) for breast cancer, and three years after excision of a single cerebral metastasis. Cerebral angiography obtained on admission showed occlusion of the right ICA and right subclavian arteries, both lesions necessitating thrombectomy. After surgery the right radial pulse immediately re-appeared and the hemiparesis regressed. In both patients, 2-year follow-up assessment by Doppler ultrasonography and magnetic resonance angiography (MRA) confirmed that the operated arteries remained patent. These two unusual cases underline the potential risk of irradiation-induced ischemic cerebrovascular symptoms, suggesting that patients who have received radiation therapy to the neck and mediastinum who survive for more than 5 years should undergo regular non-invasive imaging of neck vessels (Doppler ultrasonography and MRA).

Multiple meningiomas in different neuraxial compartments. Report of two cases.

Multiple meningiomas in different neuraxial compartments are quite rare. The authors report two new cases of association between cranial and spinal meningiomas, one of them in a patient operated upon for multiple intracranial meningiomas. The first case was a 60-year-old woman with progressive paraparesis who had been operated on 13 years earlier for multiple intracranial meningiomas. A myelo-CT scan showed a block of contrast medium at T1-T2; the lesion was removed via a standard laminectomy. The second patient was a 76-year-old woman with a 6-month history of spastic paraparesis. MRI detected an extramedullary intradural lesion at T6-T7. A cerebral MRI, performed because of the onset of seizures, showed a right parietal lesion. Removal of the thoracic lesion was followed, 6 months later, by removal of the cerebral one. Both patients presented a progressive improvement of the paraparesis and returned to normal daily activities.

Chronic subdural haematoma: a possible relationship with tamoxifen.

Five patients operated on between 6 months and 7 years earlier for breast cancer were surgically treated for chronic subdural haematoma. This unusual association may be explained on the basis of known factors such as coagulative impairment subsequent to chemotherapy, a degree of cerebral atrophy or mild trauma. On the other hand, since four of the patients were taking antioestrogen therapy to control the disease, it is speculated that the oestrogenic properties of tamoxifen may have contributed to subdural bleeding.

Activation of nuclear inositide signalling pathways during erythropoietin therapy in low-risk MDS patients.

Inositide signaling pathways can have a role in the Myelodysplastic Syndromes (MDS) progression to acute myeloid leukemia. Erythropoietin (EPO) is currently used in low-risk MDS, where it successfully corrects anemia in 50-70% of patients. However, some MDS patients are refractory to this treatment and little is known about the exact molecular mechanisms underlying the effect of EPO in these subjects. Here, we investigated the role of inositide pathways in low-risk MDS treated with EPO, mainly focusing on the Akt/PI-PLC (Phosphoinositide-Phospholipase C) gamma1 axis, which is activated by the EPO receptor, and PI-PLCbeta1/Cyclin D3 signaling, as Cyclin D3 is associated with hematopoietic proliferation and differentiation. Interestingly, EPO responder patients showed a specific activation of both the Akt/PI-PLCgamma1 pathway and beta-Globin gene expression, while nonresponders displayed an increase in PI-PLCbeta1 signaling. Moreover, in normal CD34+ cells induced to erythroid differentiation, PI-PLCbeta1 overexpression abrogated both EPO-induced Akt phosphorylation and beta-Globin expression. Overall, these findings suggest that PI-PLCbeta1 can act as a negative regulator of erythroid differentiation and confirm the involvement of Akt/PI-PLCgamma1 pathway in EPO signaling, therefore contributing to the comprehension of the effect of EPO in low-risk MDS and possibly paving the way to the identification of MDS patients at higher risk of refractoriness to EPO treatment.

Soft tissue depression at the iliac crest prominence: a new landmark for identifying the L4-L5 interspace.

BACKGROUND: One of the most common approaches to identifying the L4-L5 interspace is using the iliac crest as a landmark. We propose a new landmark to identify the L4-L5 interspace based on the soft tissue depression palpable at the iliac crest prominence. The aim of this study was to assess the reliability and time saving when using this new landmark compared to using the iliac crest to perform a lumbar plexus block. METHODS: Fifty-four patients scheduled for lower limb surgery were randomly allocated to have a lumbar plexus block performed using the iliac crest (Chayen's approach) or the soft tissue depression (Borghi's approach). The landmarks for both approaches were drawn on each patient prior to randomization (N.=27 per group). All the blocks were performed by an anesthesiologist familiar with both techniques using a nerve stimulator and 30 mL of 0.5% levobupivacaine. The time to achieve successful needle placement and the number of needle re-directions, as well as the onset time for the sensory and motor blockade, were recorded. RESULTS: All the blocks using Borghi's approach were performed successfully. With the Chayen's approach, there were 5 needle placement failures. The mean times to onset of a successful block after injection of the local anesthetic did not differ between the two groups: 17.8±3.9 min for the Chayen vs. 15.9±2.4 min for the Borghi's approach (P=0.14). However, the mean time to achieve correct needle placement was 7.6±3.2 min with the Chayen's approach compared to 5.1 (±2.6 SD) min with the Borghi's approach (P<0.01). The Chayen's approach also required a significantly higher median number of needle redirections (2 [inter-quartile range (IQR): 0-4] vs. 0 [IQR: 0-4], P<0.01). In obese patients (BMI ≥30 kg/m(2)), the mean placement time was 10.5±1.7 min vs. 4.8±2.1 min (P<0.01), and median number of needle re-directions was 2.5 (IQR: 2-3) vs. 0.5 (IQR: 0-3) (P=0.04), with the Chayen and Borghi's approach, respectively. CONCLUSION: Use of the palpable soft tissue depression at the iliac crest prominence for performing a lumbar plexus block offered several potential advantages over the standard inter-iliac crest approach.

Synergistic induction of PI-PLCß1 signaling by azacitidine and valproic acid in high-risk myelodysplastic syndromes.

The association between azacitidine (AZA) and valproic acid (VPA) has shown high response rates in high-risk myelodysplastic syndromes (MDS) cases with unfavorable prognosis. However, little is known about the molecular mechanisms underlying this therapy, and molecular markers useful to monitor the disease and the effect of the treatment are needed. Phosphoinositide-phospholipase C (PI-PLC) ß1 is involved in both genetic and epigenetic mechanisms of MDS progression to acute myeloid leukemia. Indeed, AZA as a single agent was able to induce PI-PLCß1 expression, therefore providing a promising new tool in the evaluation of response to demethylating therapies. In this study, we assessed the efficacy of the combination of AZA and VPA on inducing PI-PLCß1 expression in high-risk MDS patients. Furthermore, we observed an increase in Cyclin D3 expression, a downstream target of PI-PLCß1 signaling, therefore suggesting a potential combined activity of AZA and VPA in high-risk MDS in activating PI-PLCß1 signaling, thus affecting cell proliferation and differentiation. Taken together, our findings might open up new lines of investigations aiming at evaluating the role of the activation of PI-PLCß1 signaling in the epigenetic therapy, which may also lead to the identification of innovative targets for the epigenetic therapy of high-risk MDS.

Different isoforms of the B-cell mutator activation-induced cytidine deaminase are aberrantly expressed in BCR-ABL1-positive acute lymphoblastic leukemia patients.

The main reason for the unfavorable clinical outcome of BCR-ABL1-positive acute lymphoblastic leukemia (ALL) is genetic instability. However, how normal B-cell precursors acquire the genetic changes that lead to transformation has not yet been completely defined. We investigated the expression of the activation-induced cytidine deaminase (AID) and its role in clinical outcome in 61 adult BCR-ABL1-positive ALL patients. AID expression was detected in 36 patients (59%); it correlated with the BCR-ABL1 transcript levels and disappeared after treatment with tyrosine kinase inhibitors. Different AID splice variants were identified: full-length isoform; AIDDeltaE4a, with a 30-bp deletion of exon 4; AIDDeltaE4, with the exon 4 deletion; AIDins3, with the retention of intron 3; AIDDeltaE3-E4 isoform without deaminase activity. AID-FL predominantly showed cytoplasmic localization, as did the AID-DeltaE4a and AID-DeltaE3E4 variants, whereas the C-terminal-truncated AID-DeltaE4 showed a slightly increased nuclear localization pattern. AID expression correlated with a higher number of copy number alterations identified in genome-wide analysis using a single-nucleotide polymorphism array. However, the expression of AID at diagnosis was not associated with a worse prognosis. In conclusion, BCR-ABL1-positive ALL cells aberrantly express different isoforms of AID that may act as mutators outside the immunoglobulin (Ig) gene loci in promoting genetic instability.

Surgical exposure of lateral orbital lesions using a coronal scalp flap and lateral orbitozygomatic approach: clinical experience.

BACKGROUND: The lateral extraconal compartment is a typical localization of intra-orbital tumours. With the exception of anterior lesions, which can be reached by a transconjuntival route, most of these tumours are currently approached through the classic lateral orbitotomy originally described by Kronlein. We present here our experience in the management of lateral orbital lesions, using a coronal skin flap, followed by subfascial dissection of the temporalis muscle. The procedure was intended to overcome the potential drawbacks associated with the classic transtemporal approach. METHODS: The approach was used in eleven patients harbouring bone lesions of the lateral orbital wall or intra-orbital lesion of the lateral extra-ocular compartment. The postoperative results were assessed using a simple cosmetic outcome scale, which evalutated the temporalis muscle trophism and the function of the frontotemporal branch of the facial nerve. RESULTS: All lesions were satisfactorily exposed. The subfascial dissection of the temporalis muscle is a key manoeuvre which, at the same time, abolishes the risk of injury to the frontotemporal branch of the facial nerve and provides a wide exposure of the lateral orbital wall. The cosmetic outcome was excellent in 9 patients and good in 2 patients. CONCLUSIONS: The reported technique is a convenient surgical option to approach lateral intra-orbital lesions, with a minimal cosmetic impact.