ABSTRACT
The 2-pentadecyl-2-oxazoline (PEA-OXA) is a natural compound with protective action in neuro-inflammation. We have previously shown that PEA-OXA behaves as an α2 adrenergic receptor (α2AR) antagonist and a putative protean agonist on histamine H3 receptors. Recently, neuroinflammation and monoaminergic neurotransmission dysfunction has drawn particular attention in Alzheimer Disease (AD) pathophysiology. In this context, the objective of this study was to investigate the effects of the dual-acting PEA-OXA in an AD-like model in mice. A combined computational and experimental approach was used to evaluate the ability of PEA-OXA to bind α2A-AR subtype, and to investigate the effects of PEA-OXA treatment on neuropathological (behavioural and functional) effects induced by soluble Amyloid ß 1-42 (sAß1-42) intracerebroventricular injection. Computational analysis revealed the PEA-OXA ability to bind the α2A-AR, a pharmacological target for AD, in two alternative poses, one overlapping the Na+ binding site. In vivo studies indicated that chronic treatment with PEA-OXA (10 mg/kg, os) restored the cognitive (discriminative and spatial memory) deficits and social impairments induced by sAß injection. Consistently, electrophysiological analysis showed a recovery of the long-term potentiation in the hippocampus (Lateral Entorhinal Cortex-Dentate Gyrus pathway), while neuroinflammation, i.e., increased pro-inflammatory cytokines levels and microglia cells density were reduced. These data provide the basis for further investigation of the pro-cognitive aptitude of PEA-OXA by proposing it as an adjuvant in the treatment in AD, for which the available pharmacological approaches remain unsatisfactory. Moreover, this study offers new future direction in research investigating the role of α2AR in neuropsychiatric illness and therapies.
Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Mice , Animals , Amyloid beta-Peptides/toxicity , Amyloid beta-Peptides/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/prevention & control , Receptors, Adrenergic, alpha-2 , Disease Models, Animal , Social Behavior , CognitionABSTRACT
The OPERA experiment was designed to discover the vτ appearance in a vµ beam, due to neutrino oscillations. The detector, located in the underground Gran Sasso Laboratory, consisted of a nuclear photographic emulsion/lead target with a mass of about 1.25 kt, complemented by electronic detectors. It was exposed from 2008 to 2012 to the CNGS beam: an almost pure vµ beam with a baseline of 730 km, collecting a total of 1.8·1020 protons on target. The OPERA Collaboration eventually assessed the discovery of vµâvτ oscillations with a statistical significance of 6.1 σ by observing ten vτ CC interaction candidates. These events have been published on the Open Data Portal at CERN. This paper provides a detailed description of the vτ data sample to make it usable by the whole community.
ABSTRACT
The International League against Epilepsy (ILAE) proposed a diagnostic scheme for psychogenic non-epileptic seizure (PNES). The debate on ethical aspects of the diagnostic procedures is ongoing, the treatment is not standardized and management might differ according to age group. The objective was to reach an expert and stakeholder consensus on PNES management. A board comprising adult and child neurologists, neuropsychologists, psychiatrists, pharmacologists, experts in forensic medicine and bioethics as well as patients' representatives was formed. The board chose five main topics regarding PNES: diagnosis; ethical issues; psychiatric comorbidities; psychological treatment; and pharmacological treatment. After a systematic review of the literature, the board met in a consensus conference in Catanzaro (Italy). Further consultations using a model of Delphi panel were held. The global level of evidence for all topics was low. Even though most questions were formulated separately for children/adolescents and adults, no major age-related differences emerged. The board established that the approach to PNES diagnosis should comply with ILAE recommendations. Seizure induction was considered ethical, preferring the least invasive techniques. The board recommended looking carefully for mood disturbances, personality disorders and psychic trauma in persons with PNES and considering cognitive-behavioural therapy as a first-line psychological approach and pharmacological treatment to manage comorbid conditions, namely anxiety and depression. Psychogenic non-epileptic seizure management should be multidisciplinary. High-quality long-term studies are needed to standardize PNES management.
Subject(s)
Psychophysiologic Disorders/therapy , Seizures/therapy , Adult , Child , Electroencephalography/methods , Female , Humans , Male , Psychophysiologic Disorders/diagnosis , Seizures/diagnosisABSTRACT
The OPERA experiment was designed to study ν_{µ}âν_{τ} oscillations in the appearance mode in the CERN to Gran Sasso Neutrino beam (CNGS). In this Letter, we report the final analysis of the full data sample collected between 2008 and 2012, corresponding to 17.97×10^{19} protons on target. Selection criteria looser than in previous analyses have produced ten ν_{τ} candidate events, thus reducing the statistical uncertainty in the measurement of the oscillation parameters and of ν_{τ} properties. A multivariate approach for event identification has been applied to the candidate events and the discovery of ν_{τ} appearance is confirmed with an improved significance level of 6.1σ. |Δm_{32}^{2}| has been measured, in appearance mode, with an accuracy of 20%. The measurement of the ν_{τ} charged-current cross section, for the first time with a negligible contamination from ν[over ¯]_{τ}, and the first direct evidence for the ν_{τ} lepton number are also reported.
ABSTRACT
Since sperm require high energy levels to perform their specialised function, it is vital that essential nutrients are available for spermatozoa when they develop, capacitate and acquire motility. However, they are vulnerable to a lack of energy and excess amounts of reactive oxygen species, which can impair sperm function, lead to immotility, acrosomal reaction impairment, DNA fragmentation and cell death. This monocentric, randomised, double-blind, placebo-controlled trial investigated the effect of 6 months of supplementation with l-carnitine, acetyl-l-carnitine and other micronutrients on sperm quality in 104 subjects with oligo- and/or astheno- and/or teratozoospermia with or without varicocele. In 94 patients who completed the study, sperm concentration was significantly increased in supplemented patients compared to the placebo (p = .0186). Total sperm count also increased significantly (p = .0117) in the supplemented group as compared to the placebo group. Both, progressive and total motility were higher in supplemented patients (p = .0088 and p = .0120, respectively). Although pregnancy rate was not an endpoint of the study, of the 12 pregnancies that occurred during the follow-up, 10 were reported in the supplementation group. In general, all these changes were more evident in varicocele patients. In conclusion, supplementation with metabolic and antioxidant compounds could be efficacious when included in strategies to improve fertility.
Subject(s)
Antioxidants/therapeutic use , Asthenozoospermia/drug therapy , Varicocele/drug therapy , Adolescent , Adult , Antioxidants/pharmacology , Asthenozoospermia/complications , Dietary Supplements , Double-Blind Method , Humans , Male , Middle Aged , Sperm Motility/drug effects , Spermatozoa/drug effects , Treatment Outcome , Varicocele/complications , Young AdultABSTRACT
We present the use of a modified corporoplasty, based on geometrical principles, to determine the exact site for the incision in the tunica or plaque and the exact amount of albuginea for overlaying to correct with extreme precision the different types of congenital or acquired penile curvature due to Peyronie's disease. To describe our experience with a new surgical procedure for the enhancement of penile curvature avoiding any overcorrection or undercorrection. Between March 2004 and April 2013, a total of 74 patients underwent the geometrical modified corporoplasty. All patients had congenital curvature until 90° or acquired stable penile curvature 'less' than 60°, that made sexual intercourse very difficult or impossible, normal erectile function, absence of hourglass or hinge effect. Preoperative testing included a physical examination, 3 photographs (frontal, dorsal and lateral) of penis during erection, a 10 mcg PGE1-induced erection and Doppler ultrasound, administration of the International Index of Erectile Function (IIEF-15) questionnaire. A follow-up with postoperative evaluation at 12 weeks, 12 and 24 months, included the same preoperative testing. Satisfaction rates were better assessed with the use of validated questionnaire such as the International Erectile Dysfunction Inventory of the Treatment Satisfaction (EDITS). Statistical analysis with Student's t-test was performed using commercially available, personal computer software. A total of 25 patients had congenital penile curvature with a mean deviation of 46.8° (range 40-90), another 49 patients had Peyronie's disease with a mean deviation of 58.4 (range 45-60). No major complications were reported. Postoperative correction of the curvature was achieved in all patients (100%). Neither undercorrection nor overcorrection were recorded. No significant relapse (curvature>15°) occurred in our patients. Shortening of the penis was reported by 74% but did not influence the high overall satisfaction of 92% (patients completely satisfied with their sexual life). The erectile function was analyzed in both groups, Student's t-test showed a significant improvement in erectile function, preoperative average IIEF-15 scores were 17.43±4.67, whereas postoperatively it was 22.57±4.83 (P=0.001). This geometrical modified Nesbit corporoplasty is a valid therapy which allows penile straightening. The geometric principles make the technique reproducible in multicentre studies.
Subject(s)
Patient Satisfaction , Penile Induration/surgery , Penis/surgery , Urologic Surgical Procedures, Male/methods , Adolescent , Adult , Aged , Humans , Male , Middle Aged , Penile Erection , Postoperative Period , Treatment Outcome , Young AdultABSTRACT
Erectile dysfunction (ED), the second most common male sexual disorder, has an important impact on man sexuality and quality of life affecting also female partner's sexual life. ED is usually related to cardiovascular disease or is an iatrogenic cause of pelvic surgery. Many non-surgical treatments have been developed with results that are controversial, while surgical treatment has reached high levels of satisfaction. The aim is to evaluate outcomes and complications related to prosthesis implant in patients suffering from ED not responding to conventional medical therapy or reporting side effects with such a therapy. One hundred eighty Caucasian male suffering from ED were selected. The patient population were divided into two groups: 84 patients with diabetes and metabolic syndrome (group A) and 96 patients with dysfunction following laparoscopic radical prostatectomy for prostate cancer (group B). All subjects underwent primary inflatable penile prosthesis implant with an infrapubic minimally invasive approach. During 12 months of follow-up, we reported 3 (1.67%) explants for infection, 1 (0.56%) urethral erosion, 1 (0.56%) prosthesis extrusion while no intraoperative complications were reported. Mean International Index of Erectile Function-5 (IIEF-5) was 8.2 ± 4.0 and after the surgery (12 months later) was 20.6 ± 2.7. The improvement after the implant is significant in both groups without a statistically significant difference between the two groups (P-value 0.65). Mean Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) score 1 year after the implant is 72.2 ± 20.7, and there was no statistically significant difference between groups A and B (P-value 0.55). Implantation of an inflatable prosthesis, for treatment of ED, is a safe and efficacious approach; and the patient and partner satisfaction is very high. Surgical technique should be minimally invasive and latest technology equipment should be implanted in order to decrease after surgery common complications (infection and mechanical failure).
Subject(s)
Erectile Dysfunction , Metabolic Diseases/complications , Penile Implantation , Penile Prosthesis , Postoperative Complications , Prostatectomy/adverse effects , Quality of Life , Aged , Erectile Dysfunction/etiology , Erectile Dysfunction/psychology , Erectile Dysfunction/surgery , Follow-Up Studies , Humans , Male , Middle Aged , Minimally Invasive Surgical Procedures/methods , Patient Satisfaction , Penile Implantation/adverse effects , Penile Implantation/instrumentation , Penile Implantation/methods , Penile Prosthesis/adverse effects , Penile Prosthesis/psychology , Postoperative Complications/diagnosis , Postoperative Complications/prevention & control , Prostatectomy/methods , Prostatic Neoplasms/surgery , Treatment OutcomeABSTRACT
Purpose: Regulation of the apoptotic process has an important role in spermatogenesis. p53 has a prominent function in apoptosis and recent data suggest a relationship between varicocele and p53 codon 72 polymorphism and male infertility. This prompted us to study the relationship between this polymorphism and spermatic parameters. Methods: We studied 134 subjects with varicocele admitted consecutively to the outpatients Department of Infertility at the University of Rome La Sapienza. We investigated in these subjects the effect of a strong apoptosis inducer, the p53 codon 72 *Arg/*Arg genotype, on spermatic parameters.The p53 codon 72 genotype was determined by DNA analysis. Results: The proportion of spermatozoa with abnormal (curvilinear) motility is higher in men with the *Arg/*Arg genotype than in men carrying the *Pro allele (p = 0.003). No statistical significant relationship has been observed with spermatozoa concentration and atypical spermatozoa. Conclusions: We conclude: the p53 codon 72*Arg/*Arg genotype, with its strong apoptotic effects, negatively influences spermatozoa motility and male fertility.
ABSTRACT
Bladder carcinoma (BC) is the most common urinary malignant tumor. In the light of the unsuccessful current therapies and their side effects, new pharmacological strategies are needed. In addition to the well known therapeutic possibilities described in the first section, we focused our attention on very recent and innovative tools to approach this target (new drug candidates from epigenetic modulators to endothelin receptor inhibitors, improved technological formulations, active principles from plants, and dietary components). Then, in the last paragraph, we analyzed the etiology of recurrent BC, with particular attention to cellular microenvironment. In fact, the incidence of recurrence is up to 90%, and 25% of tumours show progression towards invasiveness.
Subject(s)
Antineoplastic Agents/therapeutic use , Urinary Bladder Neoplasms/therapy , Animals , Antineoplastic Agents/chemistry , Humans , Molecular Targeted Therapy , Neoplasm Invasiveness , Neoplasm Metastasis , Recurrence , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/geneticsABSTRACT
Platelet-derived growth factor (PDGF) and its receptors (PDGFRs) play a key role in the regulation of the embryonic and postnatal development of male gonads. PDGF deficiency is associated with severe spermatogenic impairment. ACP1 is a phosphoprotein tyrosine phosphatase that is able to dephosphorylate PDGFR, decreasing its activity as growth factor. The enzyme is polymorphic and shows strong differences in enzymatic activity among genotypes. At the Outpatient Department for Infertility, University of Rome La Sapienza, we investigated the effect of high-activity ACP1 genotype on spermatic parameters in 105 subjects referred to for varicocele. ACP1 genotype was determined by DNA analysis. In ACP1 *B/*C genotype, which shows the highest enzymatic activity, spermatic concentration is significantly lower and atypical spermatozoa are significantly more frequent as compared to other ACP1 genotypes. It is concluded that subjects carrying *B/*C genotype who represent about 10% of the population have a severe impairment of spermatic parameters in the presence of varicocele.
Subject(s)
Infertility, Male/genetics , Protein Tyrosine Phosphatases/genetics , Proto-Oncogene Proteins/genetics , Spermatozoa/physiology , Varicocele/genetics , Adult , Genotype , Humans , Male , Polymorphism, Single Nucleotide , Receptors, Platelet-Derived Growth Factor/metabolismABSTRACT
OBJECTIVE: To analyze feasibility and outcomes of laparoscopic partial nephrectomy (LPN) for endophytic hilar tumors in low-intermediate (ASA I-II) risk patients. METHODS: This is a single centre retrospective study. From May 2009 to September 2011, 208 LPNs were performed at our institution. Overall 11 (5.2%) elective LPNs were for hilar tumors not visible on kidney surface. Hilar tumor was defined as a mass located in the renal hilum and in contact with a major renal vessel on preoperative imaging. Procedures were carried out by a single experienced surgeon (G.G.) via retroperitoneal approach by clamping the only main renal artery. RESULTS: Mean (range) age of patients was 45.3 years (38.2-64.1), tumor size 1.6 cm (1.2-2.0), warm ischemia time 24 min (19-32), operative time 140 min (110-200) and estimated blood loss 270 ml (100-750). Two collecting system injuries were observed and repaired intraoperatively. No conversion to open surgery was required. Final pathological examination revealed 10 renal cell carcinomas and 1 oncocytoma. A negative surgical margin was obtained in 10/11 (91%) patients. Renal function and serum hemoglobin were nearly unaltered pre and post-surgery. No tumor recurrence was observed at mean (range) follow-up of 34 months (15-43). CONCLUSIONS: In experienced hands, LPN represents a feasible, safe and effective treatment for selected patients diagnosed with endophytic hilar masses. A larger number of patients and longer follow-up are required to draw definitive conclusions.
Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Laparoscopy/methods , Nephrectomy/methods , Adult , Carcinoma, Renal Cell/pathology , Feasibility Studies , Female , Humans , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local , Operative Time , Retrospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION: Cystosarcoma phyllodes are very rare tumors and may be difficult to diagnose clinically. BACKGROUND: Fibroadenomas have long been considered benign hyperplastic lesions rather than true neoplastic processes. However, previous clonality studies have shown differing results. AIM: to assess diagnostic and treatment options for phyllodes tumor. MATERIALS AND METHODS: A 41-year-old female patient undergoing assisted fertilization treatment. The patient underwent fine needle aspiration biopsy that confirmed fibroadenoma before the IVF attempt. At 17 weeks of gestation, due to an increase in volume of the fibroadenoma, an excisional biopsy was performer that showed a malignant phyllodes tumor. Then she underwent quadrantectomy and chemiotherapy After 1 year there was a recurrence of phyllodes tumors and she underwent mastectomy and chemotherapy. RESULTS: Fibroadenoma that was transformed into high-grade malignant cystosarcoma after ovarian stimulation, relapsed after one year and it was not immediately diagnosed. The patient underwent mastectomy and chemotherapy. DISCUSSION: it is difficult to diagnose recurrence and to determine tele frequency and the right treatment for such a rare cancer, so it is important to report any case in the literature. CONCLUSIONS: We recommend to remove a fibroadenoma before attempting IVF for the risk of malignant transformation.
Subject(s)
Breast Neoplasms/pathology , Cell Transformation, Neoplastic , Fibroadenoma/pathology , Neoplasm Recurrence, Local/diagnosis , Phyllodes Tumor/pathology , Adult , Biopsy, Fine-Needle , Diagnostic Errors , Female , Fertilization in Vitro , Humans , Neoplasm GradingABSTRACT
BACKGROUND: Circulating tumor cells (CTCs) provide prognostic information in patients with metastatic tumors. Recent studies have shown that CTCs are released in circulation in an early phase of cancer disease so that their presence is under investigation in the adjuvant setting. Few studies investigated the prognostic significance of CTCs enumeration in patients with metastatic and advanced bladder cancer. The current study has analyzed the presence of CTC in patients with nonmuscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Forty-four NMIBC patients were enrolled and included in a 24-month follow-up program. Blood drawings were carried out in all patients at the first diagnosis. CellSearch system (Veridex; LLC, Raritan, NJ) was used for CTCs enumeration. RESULTS: CTC were detectable in 8/44 patients (18%). Presence of CTC was found significantly associated to shorter time to first recurrence (6.5 versus 21.7 months, P < 0.001). Median time to progression was not reached, due to the short follow-up period. CTC presence was found associated to concomitant carcinoma in situ and higher T category. CONCLUSION: The detection of CTC in this setting of disease may allow to distinguish patients with high risk of recurrence from those with high risk of progression, as well as to early identify patients candidate for adjuvant treatment.
Subject(s)
Carcinoma, Transitional Cell/pathology , Neoplasm Recurrence, Local , Neoplastic Cells, Circulating/pathology , Urinary Bladder Neoplasms/pathology , Aged , Case-Control Studies , Cell Count , Chi-Square Distribution , Disease-Free Survival , Female , Follow-Up Studies , Humans , Immunomagnetic Separation , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Invasiveness , Prognosis , Prospective Studies , Treatment OutcomeABSTRACT
Small cell carcinoma of the urinary bladder (SCCUB) is a rare variant of neuroendocrine nonepithelial tumor. Clinically, SCCUB appears like a flat or ulcerated lesion and microscopically can cause microvascular invasion and necrosis. Small cell cancer, rarely found in the urogenital tract in a primitive form, usually coexists with urothelial bladder cancers. It has an incidence of 0.35-0.7% of all bladder neoplasms and survival at 5 years is estimated to be around 8%. A 60-year-old man who was a smoker was referred to our department with episodes of gross hematuria and pain in the lumbar region. After an extensive transurethral resection of the bladder, including of the muscular layer, the diagnosis of small cell carcinoma of the bladder was made. The neoplastic cells were positive with immunohistochemical staining for chromogranin A, paranuclear reactivity to cytokeratin and neuron-specific enolase. A total-body CT scan revealed lymph node involvement and hepatic, adrenal and lung metastases. Because of the advanced stage it was decided to avoid radical cystectomy and perform chemotherapy. The patient underwent two different cycles of cisplatin chemotherapy following international recommendations, but unfortunately without any response. After palliative therapy, the patient died in January 2010.
Subject(s)
Carcinoma, Neuroendocrine/secondary , Carcinoma, Small Cell/secondary , Urinary Bladder Neoplasms/pathology , Adrenal Gland Neoplasms/secondary , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Carcinoma, Neuroendocrine/chemistry , Carcinoma, Neuroendocrine/drug therapy , Carcinoma, Small Cell/chemistry , Carcinoma, Small Cell/drug therapy , Fatal Outcome , Humans , Immunohistochemistry , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Small Cell Lung Carcinoma/secondary , Tomography, X-Ray Computed , Treatment Outcome , Urinary Bladder Neoplasms/chemistry , Urinary Bladder Neoplasms/drug therapy , Whole Body ImagingABSTRACT
BACKGROUND: The management of stage T1 poorly differentiated G3 bladder cancer invading the lamina propria continues to be debated. These tumours are associated with a high risk of recurrence and progression; concomitant carcinoma in situ and/or multifocality are negative prognostic factors. Choosing between a preserving approach such as trans-urethral resection of the bladder (TURB) followed by maintenance bacillus Calmette-Guerin (BCG) and an invasive approach like cystectomy is critical. PATIENTS AND METHODS: Overall, 80 patients underwent TURB and RE-TURB followed by intra-vesical induction treatment with BCG plus maintenance (Group A) while 72 patients underwent immediate radical cystectomy with extended lymphadenectomy (Group B). Patients were divided into 3 subgroups: uni-focal tumours, multi-focal tumours and carcinoma in situ associated lesions. In Group A, time to first recurrence and time to progression were analysed. A comparison was made between Group A and Group B regarding progression-free survival, cancer-specific survival and overall survival with a median follow-up time of 8.3 years. RESULTS: As far as concerns Group A patients, 42 recurrences (52.5%) were reported in a median time of 10.4 months (range 3-26) and 25 progressions (31.2%) in a median time of 25 months (range 3-68). As far as concerns time to first recurrence and time to progression, both the Kaplan-Meier survival curves obtained are significant and P values are, respectively, 0.0263 and 0.0011. Comparing Groups A and B patients, 25 progressions (31.2%) in a median time of 25 months (range 3-68) and 18 progressions (25%) in a median time of 25.9 months (range 4-72), respectively, were recorded. Regarding overall survival, at 10 years, 24 deaths (42.5%) occurred in a median time of 55.4 months (range 12-94) in Group A and 42 deaths (58.3%) in a median time of 54.9 months (10-100) in Group B. Cancer-specific survival was evaluated in Group A with a total of 18 deaths (22.5%) in a median time of 47.5 months (range 16-78), and in Group B with a total of 16 deaths (22.2%) in a median time of 45.7 months (range 16-88). The progression-free survival Kaplan-Meier curve is not significant, the P value being 0.3801; the overall survival curve is significant with a P value of 0.0487 while the cancer-specific survival curve is not significant with a P value of 0.9762. DISCUSSION: In Group A, considering "time to first recurrence", the difference is greater between unifocal lesions and multifocal or Cis-associated lesions. Conversely, for "time to progression", there is a greater difference between unifocal and multifocal tumours and Cis-associated tumours. Looking at "progression-free survival" in Group A and Group B patients, there is no statistically significant difference, like in cancer-specific survival. A statistically significant difference was observed in overall survival being in favour of conservative treatment thus reflecting that conservative treatment is not burdened by all the surgical and post-operative complications of cystectomy. CONCLUSIONS: Although NMIBC invading the lamina propria, stage G3, with or without Cis-associated lesions are burdened both by a high volume of recurrences and progressions, cystectomy could be considered an aggressive approach. New biological markers are now needed which are able to predict the behaviour of the cancer and to guide the decision-making process between conservative or aggressive treatment.
Subject(s)
Carcinoma in Situ/therapy , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/therapy , Neoplasm Recurrence, Local/etiology , Neoplasms, Multiple Primary/therapy , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/therapy , Adult , Aged , Aged, 80 and over , BCG Vaccine/therapeutic use , Carcinoma in Situ/pathology , Cystectomy , Disease Progression , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Mucous Membrane/pathology , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Neoplasms, Multiple Primary/pathology , Prognosis , Retrospective Studies , Time FactorsABSTRACT
Established beliefs concerning outcomes following anterior urethral reconstruction are changing, both with regards to the genital cosmetics and to the impact on sexual activity. Today, the aim of stricture repair is not only to reinstate urinary function but also to safeguard sexual activity and guarantee genital cosmesis. A thorough evaluation of anterior urethroplasty results should include the sexual viewpoint which appears to play an important role in overall post-operative patient satisfaction. The most commonly reported sexual problems following anterior urethroplasty include: erectile and ejaculatory dysfunction, penile curvature or shortening, dissatisfaction with genital cosmetic appearance, sensorial impairment of glans. The prevalence of specific post-operative sexual problems may be related to the site of reconstruction (penile or bulbar) and to the technique of urethroplasty employed. In penile urethral reconstruction, the wide use of buccal mucosa grafts seems to excel the use of skin flaps which easily distort the cosmesis and elasticity of the penis. In bulbar reconstructions, graft augmentation techniques seem to impact less on sexual outcome than excision anastomotic techniques. Therefore, the policy of primarily indicating an excision anastomotic procedure, whenever possible, should come under scrutiny. Eventual sexual outcomes should be incorporated in the choice of the optimal anterior urethral reconstruction and in pre-operative patient counselling.
Subject(s)
Mouth Mucosa/transplantation , Penis/surgery , Surgical Flaps , Urethral Stricture/surgery , Urologic Surgical Procedures, Male/methods , Humans , Male , Penile Erection , Treatment OutcomeABSTRACT
PURPOSE: The purpose of this study was to evaluate the role of magnetic resonance spectroscopic imaging (MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in detecting tumour foci in patients with elevated prostate-specific antigen (PSA) and negative transrectal ultrasonography (TRUS)-guided biopsy. MATERIALS AND METHODS: This prospective randomised trial was conducted on 150 patients who underwent [¹H]MRSI and DCE-MRI and targeted biopsies of suspicious areas on MRI associated with random biopsies. RESULTS: After the second biopsy, the diagnosis of prostate adenocarcinoma was made in 64/150 cases. On a per-patient basis, MRSI had 82.8% sensitivity, 91.8% specificity, 88.3% positive predictive value (PPV), 87.8% negative predictive value (NPV) and 85.7% diagnostic accuracy. The sensitivity, specificity, PPV, NPV and accuracy for DCE-MRI was 76.5%, 89.5%, 84.5%, 83.7% and 82%, respectively. The combination of MRSI and DCE-MRI yielded 93.7% sensitivity, 90.7% specificity, 88.2% PPV, 95.1% NPV and 90.9% accuracy in detecting prostate carcinoma. CONCLUSIONS: The combined study with [¹H]MRSI and DCE-MRI showed promising results in guiding the biopsy of cancer foci in patients with an initial negative TRUS-guided biopsy.
Subject(s)
Adenocarcinoma/diagnosis , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methods , Prostatic Neoplasms/diagnosis , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Aged , Biopsy, Needle , Contrast Media , Humans , Image Interpretation, Computer-Assisted , Logistic Models , Male , Middle Aged , Organometallic Compounds , Predictive Value of Tests , Prospective Studies , Prostate-Specific Antigen/analysis , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , ROC Curve , Sensitivity and Specificity , Ultrasonography, InterventionalABSTRACT
The International League Against Epilepsy (ILAE) classification recognizes 2 forms of myoclonic epilepsy with a good prognosis: benign myoclonic epilepsy of infancy (BMEI) and juvenile myoclonic epilepsy (JME); recent studies confirm the efficacy of levetiracetam (LEV) in treating idiopathic generalized epilepsies (IGE) in patients with myoclonic seizures. We report a girl referred to our Child Neuropsychiatry Unit at age 9 years because of massive myoclonic jerks, previously diagnosed as tics. Neuropsychological examination evidenced mild cognitive impairment. The clinical and electroencephalogram (EEG) data led to diagnosis of BMEI with late presentation. A dramatic suppression of interictal and ictal epileptiform activity was achieved after only one intake of LEV. Another neuropsychological examination after 6 months of treatment showed performance improvement probably related to EEG modifications. LEV may be suitable for the first-line treatment of myoclonic idiopathic seizures.
Subject(s)
Anticonvulsants/therapeutic use , Epilepsies, Myoclonic/drug therapy , Myoclonus/drug therapy , Piracetam/analogs & derivatives , Child , Cognition Disorders/complications , Electroencephalography , Epilepsies, Myoclonic/complications , Epilepsies, Myoclonic/diagnosis , Female , Humans , Levetiracetam , Myoclonus/complications , Myoclonus/diagnosis , Neuropsychological Tests , Piracetam/therapeutic use , Treatment OutcomeABSTRACT
Transglutaminases are a large family of related and ubiquitous enzymes which catalyze the cross linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono- or bi-substituted /crosslinked adducts) or -OH groups (to form ester linkages). In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. These enzymes are also capable of catalyzing other reactions important for cell viability. The distribution and the physiological roles of human transglutaminases have been widely studied in numerous cell types and tissues and their roles in several diseases have begun to be identified. Recently, "tissue" transglutaminase (TG2) has been shown to be involved in the molecular mechanisms responsible for a very widespread human pathology, celiac disease (CD). Transglutaminase activity has also been hypothesized to be directly involved in the pathogenetic mechanisms responsible for several human neurodegenerative diseases, which are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains, such as Alzheimer's disease (AD), Parkinson's disease (PD), supranuclear palsy, Huntington's disease (HD) and the other recently identified polyglutamine diseases, and others. In this review we discuss the biological role of the transglutaminases in the nervous system, with particular interest in the molecular mechanisms, which could involve these enzymes in the pathophysiological processes responsible for human neurodegenerative diseases.
Subject(s)
Central Nervous System/enzymology , Neurodegenerative Diseases/enzymology , Transglutaminases/physiology , Brain/enzymology , Brain/metabolism , Celiac Disease/enzymology , Celiac Disease/physiopathology , Humans , Neurodegenerative Diseases/physiopathology , Peptides/metabolism , Peptides/physiology , Transglutaminases/metabolismABSTRACT
Transglutaminases are a large family of related and ubiquitous enzymes which catalyze the cross-linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate. These enzymes are also capable of catalyzing other reactions important for the cell viability. The distribution and the physiological roles of the human transglutaminases have been widely studied in numerous cell types and tissues and their roles in several diseases have begun to be identified. Recently, "tissue" transglutaminase (TG2) has been shown to be involved in the molecular mechanisms responsible for a very widespread human pathology, Celiac Disease (CD). Transglutaminase activity has also been hypothesized to be directly involved in the pathogenetic mechanisms responsible for several human neurodegenerative diseases, which are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains, such as Alzheimer's disease (AD), Parkinson's disease (PD), supranuclear palsy, Huntington's disease (HD) and other recently identified polyglutamine diseases. In this review we discuss the biochemistry of the transglutaminases, with particular reference to the molecular mechanisms that could be involved in the physiopathological processes responsible for these human neurodegenerative diseases.