Sample records for recurrent primary cns

  1. AZD2171 in Treating Young Patients With Recurrent, Progressive, or Refractory Primary CNS Tumors


    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma

  2. Pembrolizumab: first experience with recurrent primary central nervous system (CNS) tumors.

    Blumenthal, Deborah T; Yalon, Michal; Vainer, Gilad W; Lossos, Alexander; Yust, Shlomit; Tzach, Lior; Cagnano, Emanuela; Limon, Dror; Bokstein, Felix


    Patients with progressive primary brain tumors (PBT) are attracted to promising new treatments, even prior to convincing data. Anti-PD1 immunotherapies have been in the spotlight since publication of groundbreaking results for metastatic melanoma with pembrolizumab (PBL). Our objective was to report on the response and toxicity of PBL in patients with advanced PBT. We retrospectively reviewed the charts of 22 patients (17 adults and 5 children) with recurrent central nervous system tumors treated with PBL. We analyzed prior antineoplastic therapies, steroid usage, and outcomes. Patients received a median of two neoplastic therapies prior to PBL, and a median of three infusions of PBL in adults and four in children. Twelve patients (9 adults and 3 children) started PBL on steroids (median dose in adults 4 mg; range 2-8, and in children 1.5 mg, range 0.5-4) and five patients received steroids later during PBL treatment. Twelve patients (10 adults and 2 children) received concomitant bevacizumab with PBL. Side effects were minimal. All patients showed progressive tumor growth during therapy. Median OS from the start of PBL was 2.6 months in adults and 3.2 months in children. Two GB patients underwent tumor resection following treatment with PBL. Tumor-lymphocytic response in these cases was unremarkable, and PD-L1 immuno-staining was negative. In this series of 22 patients with recurrent primary brain tumors, PBL showed no clinical or histologic efficacy. We do not recommend further use of PBL for recurrent PBT unless convincing prospective clinical trial data are published.

  3. General Information about Primary CNS Lymphoma

    ... Research Primary CNS Lymphoma Treatment (PDQ®)–Patient Version General Information About Primary CNS Lymphoma Go to Health ... start in the eye (called ocular lymphoma). Enlarge Anatomy of the lymph system, showing the lymph vessels ...

  4. Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide

    Enting, Roeline; Demopoulos, A; DeAngelis, LM; Abrey, LE


    The authors evaluated the efficacy of a combination of rituximab and temozolomide for recurrent or refractory primary CNS lymphoma (PCNSL). Fifteen patients with a median age of 69 years had a 53% objective response rate with acceptable toxicity. Median overall survival is 14 months and median progr

  5. Primary CNS vasculitis presenting as intraventricular bleeding

    Pillai, Sreeja Hareendranathan; Sreedharan, Sapna Erat; Menon, Girish; Kannoth, Santhosh; PN, Sylaja


    Primary angiitis of the central nervous system (PACNS) is a rare disorder affecting both medium- and small-sized vessels. Intracranial haemorrhages though less reported are in the form of parenchymal haemorrhage and subarachnoid haemorrhage. We report a case of PACNS with intraventricular haemorrhage due to aneurysms secondary to progression of vasculitis. PMID:27570401

  6. Recurrent Primary Spinal Hydatid Cyst

    Okan Turk


    Full Text Available Primary hydatid disease of spine is rare and spinal hydatitosis constitute only 1% of all hydatitosis. We report a case of recurrent primary intraspinal extradural hydatid cyst of the thoracic region causing progressive paraparesis. The patient was operated 16 years ago for primary spinal hydatid disease involvement and was instrumented dorsally for stabilization. The magnetic resonance imaging (MRI of thoracic spine showed a cystic lesion at T11-12 level and compressed spinal cord posterolaterally. Intraspinal cyst was excised through T11-12 laminectomy which made formerly. The early postoperative period showed a progressive improvement of his neurological deficit and he was discharged with antihelmintic treatment consisting of albendazole and amoxicillin-sulbactam combination. [Cukurova Med J 2015; 40(Suppl 1: 84-89

  7. Surgical management of primary and recurrent melanoma.

    Farma, Jeffrey M; Kulkarni, Nandini; Hsu, Cary


    Melanoma accounts for less than 2% of skin cancer cases but causes most skin cancer-related deaths. Surgery continues to be the cornerstone of treatment of melanoma and surgical principles are guided by data derived from clinical research. This article examines the evolution of surgical techniques for the diagnosis and treatment of primary and locally recurrent melanoma.

  8. Lenalidomide in Treating Young Patients With Recurrent, Progressive, or Refractory CNS Tumors


    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  9. Primary CNS lymphoma in a patient treated with azathioprine

    Glesner, Matilde Kanstrup; Ocias, Lukas Frans; Larsen, Thomas Stauffer;


    with surrounding oedema. There was cerebrospinal fluid pleocytosis, and Epstein-Barr virus (EBV) DNA was detected in the spinal fluid by PCR. A brain biopsy confirmed the suspicion of primary brain lymphoma. EBV-associated primary brain lymphoma is a relevant differential diagnosis in patients with long......-standing immune suppression presenting with neurological symptoms. Detection of EBV DNA in the spinal fluid together with characteristic radiological findings may serve as a diagnostic clue for a quick diagnosis....

  10. ABT-888 and Temozolomide in Treating Young Patients With Recurrent or Refractory CNS Tumors


    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  11. Discrimination of different brain metastases and primary CNS lymphomas using morphologic criteria and diffusion tensor imaging

    Bette, S.; Wiestler, B.; Huber, T.; Boeckh-Behrens, T.; Zimmer, C.; Kirschke, J. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neuroradiology; Delbridge, C. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neuropathology; Meyer, B.; Gempt, J. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neurosurgery


    Brain metastases are a common complication of cancer and occur in about 15-40% of patients with malignancies. The aim of this retrospective study was to differentiate between metastases from different primary tumors/CNS lymphyomas using morphologic criteria, fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Morphologic criteria such as hemorrhage, cysts, pattern of contrast enhancement and location were reported in 200 consecutive patients with brain metastases/primary CNS lymphomas. FA and ADC values were measured in regions of interest (ROIs) placed in the contrast-enhancing tumor part, the necrosis and the non-enhancing peritumoral region (NEPTR). Differences between histopathological subtypes of metastases were analyzed using non-parametric tests, decision trees and hierarchical clustering analysis. Significant differences were found in morphologic criteria such as hemorrhage or pattern of contrast enhancement. In diffusion measurements, significant differences between the different tumor entities were only found in ADC analyzed in the contrast-enhancing tumor part. Among single tumor entities, primary CNS lymphomas showed significantly lower median ADC values in the contrast-enhancing tumor part (ADC{sub lymphoma} 0.92 [0.83-1.07] vs. ADC{sub no} {sub lymphoma} 1.35 [1.10-1.64] P=0.001). Further differentiation between types of metastases was not possible using FA and ADC. There were morphologic differences among the main subtypes of brain metastases/CNS lymphomas. However, due to a high variability of common types of metastases and low specificity, prospective differentiation remained challenging. DTI including FA and ADC was not a reliable tool for differentiation between different histopathological subtypes of brain metastases except for CNS lymphomas showing lower ADC values. Biopsy, surgery and staging remain essential for diagnosis.

  12. Advance statement of consent from patients with primary CNS tumours to organ donation and elective ventilation.

    Patel, Umang Jash


    A deficit in the number of organs available for transplantation persists even with an increase in donation rates. One possible choice of donor for organs that appears under-referred and/or unaccepted is patients with primary brain tumours. In spite of advances in the treatment of high-grade primary central nervous system (CNS) tumours, the prognosis remains dire. A working group on organs from donors with primary CNS tumours showed that the risk of transmission is small and outweighs the benefits of waiting for a normal donor, in survival and organ life-years, with caveats. This paper explores the possibility that, if information on organ donation were made available to patients and their families with knowledge of their inevitable fate, perhaps some will choose to donate. It would be explained that to achieve this, elective ventilation would be performed in their final moments. This would obviate the consent question because of an advance statement. It is accepted that these are sensitive matters and there will be logistic issues. This will need discussion with the public and other professionals, but it could increase the number of donors and can be extrapolated to encompass other primary CNS tumours.

  13. Primary angiitis of CNS : neuropathological study of three autopsied cases with brief review of literature.

    Panda K


    Full Text Available Primary angiitis of CNS(PACNS or granulomatous angiitis of CNS is a rare inflammatory disease of small blood vessels mostly confined to the CNS. The clinical and pathological features of 3 autopsied cases are described. Clinically all the three PACNS patients were young males, age ranging from 19 to 31 years. All presented with varied neurological manifestations. There was no evidence of systemic disease in any of the cases. The ESR was normal and CSF analysis showed chronic meningitic pattern. The cerebral angiogram in one case was normal and the CT scan done in another case showed multiple intracerebral haematoma due to vasculitis. Brain biopsy was not done. Diagnosis was made at post-mortem examination. Histology showed characteristic but variable degree of granulomatous and non-granulomatous angiitis of small vessels. Venulitis with parenchymal haemorrhages was the predominant feature and in one case phlebitis with thrombosis was noted. Since the disease responds to steroids and immunosuppressive therapy, establishing antemortem diagnosis is important. In view of the association of angiitis of CNS with bacteria and viral infections, their role in the evolution of the disease needs to be investigated.

  14. Toxicity and in vitro activity of HIV-1 latency-reversing agents in primary CNS cells.

    Gray, Lachlan R; On, Hung; Roberts, Emma; Lu, Hao K; Moso, Michael A; Raison, Jacqueline A; Papaioannou, Catherine; Cheng, Wan-Jung; Ellett, Anne M; Jacobson, Jonathan C; Purcell, Damian F J; Wesselingh, Steve L; Gorry, Paul R; Lewin, Sharon R; Churchill, Melissa J


    Despite the success of combination antiretroviral therapy (cART), HIV persists in long lived latently infected cells in the blood and tissue, and treatment is required lifelong. Recent clinical studies have trialed latency-reversing agents (LRA) as a method to eliminate latently infected cells; however, the effects of LRA on the central nervous system (CNS), a well-known site of virus persistence on cART, are unknown. In this study, we evaluated the toxicity and potency of a panel of commonly used and well-known LRA (panobinostat, romidepsin, vorinostat, chaetocin, disulfiram, hexamethylene bisacetamide [HMBA], and JQ-1) in primary fetal astrocytes (PFA) as well as monocyte-derived macrophages as a cellular model for brain perivascular macrophages. We show that most LRA are non-toxic in these cells at therapeutic concentrations. Additionally, romidepsin, JQ-1, and panobinostat were the most potent at inducing viral transcription, with greater magnitude observed in PFA. In contrast, vorinostat, chaetocin, disulfiram, and HMBA all demonstrated little or no induction of viral transcription. Together, these data suggest that some LRA could potentially activate transcription in latently infected cells in the CNS. We recommend that future trials of LRA also examine the effects of these agents on the CNS via examination of cerebrospinal fluid.

  15. A reliable primary human CNS culture protocol for morphological studies of dendritic and synaptic elements.

    Hammond, Robert R; Iskander, Sam; Achim, Cristian L; Hearn, Stephen; Nassif, Jane; Wiley, Clayton A


    Primary dissociated human fetal forebrain cultures were grown in defined serum-free conditions. At 4 weeks in vitro the cultures contained abundant morphologically well differentiated neurons with complex dendritic arbors. Astrocytic proliferation was negligible without the use of antimitotic agents. Confocal scanning laser microscopy (CSLM) and electron microscopy confirmed the presence of a dense neuropil, numerous cell-cell contacts and synapses. Neurons expressed a variety of proteins including growth associated protein-43 (GAP43), microtubule associated protein-2ab (MAP), class-III beta tubulin (C3BT), neurofilaments (NF), synaptophysin (SYN), parvalbumin (PA) and calbindin (CB). The cultures have proven to be reliable and simple to initiate and maintain for many weeks without passaging. They are useful in investigations of dendritic growth and injury of primary human CNS neurons.

  16. Primary Recurrence in the Lung is Related to Favorable Prognosis in Patients with Pancreatic Cancer and Postoperative Recurrence.

    Zheng, Biao; Ohuchida, Kenoki; Yan, Zilong; Okumura, Takashi; Ohtsuka, Takao; Nakamura, Masafumi


    The pattern of recurrence affects the clinical outcome in tumor patients. However, the clinical significance of lung metastasis as the primary recurrence site after resection in patients with pancreatic cancer remains unclear. This study aimed to clarify the clinical significance of the primary recurrence site in patients with pancreatic cancer, in terms of prognosis and clinicopathological features. This retrospective cohort study included 220 patients with postoperative recurrence after pancreatectomy for pancreatic cancer and classified by primary site of recurrence. We focused on patients with lung metastasis as the primary recurrence and investigated its correlation with prognosis and clinicopathological factors. Twenty-four (11%) patients had lung metastasis as the primary recurrence. This recurrence pattern had the best prognosis among all recurrence patterns, including liver metastasis and local recurrence. Patients with lung metastasis as the primary recurrence had favorable overall survival and survival from the date of recurrence compared with patients with other primary recurrence sites in both univariate (P = 0.0008 and P = 0.0005) and multivariate analyses (P = 0.0051 and P = 0.0068). In terms of clinicopathological features of resected pancreatic tumors, lung metastasis as the primary recurrence was associated with lower tumor stage and histologic grade, and less vascular invasion and residual tumor volume than liver metastasis. Pancreatic cancer patients with lung metastasis as the primary recurrence after pancreatectomy have a better prognosis than those with other recurrence patterns.

  17. [NMDA receptor encephalitis in the course of recurrent CNS demyelinating disorders: a case report].

    Yamamoto, Masanari; Kokubun, Norito; Watanabe, Yuka; Okabe, Ryuta; Nakamura, Toshiki; Hirata, Koichi


    We present the case of a 31-year-old woman who developed N-methyl-d-aspartate (NMDA) receptor encephalitis during the course of relapsing and remitting multiple brain lesions. The patient developed a tingling sensation in the left upper and lower extremities, and was first admitted to our hospital at age 27. She was tentatively diagnosed with multiple sclerosis on the basis of multiple lesions with Gd-enhancement in the brainstem, and 2 separate clinical relapses by age 28. At age 31, she developed a headache and pyrexia, followed by confusion and abnormal behavior. Her symptoms acutely progressed to stupor, and subsequently, she developed oral dyskinesia and athetosis-like involuntary movement of the left arm. The stupor state continued over 2 months. However, she had completely recovered by 3 months after the onset of psychiatric symptoms. Her serum and CSF samples tested positive for anti-NMDA receptor antibodies, and she was diagnosed with NMDA receptor encephalitis. Her serum was negative for anti-AQP4 antibody, but showed weak positivity for antinuclear antibody. Between ages 32 and 34, she experienced 2 clinical relapses, including right-hand clumsiness, confusion, aphasia, and dysphagia. FLAIR images showed a high-intensity area in the brain stem, thalamus, and subcortical white matter. No tumors were found throughout the course. A clinical entity of NMDA receptor encephalitis can include various neurologic disorders, such as the development of recurrent demyelinating brain lesions. Further investigation is required to clarify the pathophysiological role of anti-NMDA receptor antibody in our patient.

  18. Late relapses in primary CNS lymphoma after complete remissions with high-dose methotrexate monotherapy

    Ambady, Prakash; Holdhoff, Matthias; Bonekamp, David; Wong, Fay; Grossman, Stuart A


    Treatment of patients with newly diagnosed primary CNS lymphomas using high dose methotrexate regimens is reported to yield about 30% long term survivors with minimal neurotoxicity. As in other systemic large cell lymphomas, it is generally assumed that most relapses occur within 5 years of diagnosis. A retrospective review of the Johns Hopkins experience in 52 patients treated between 1995 and 2008 yielded 19 patients (37%) who achieved a complete response and were followed for over 5 years. Four of these patients remained progression-free for over 10 years. However, two of these long-term survivors have now relapsed over 10 years after their initial diagnosis. An analysis of progression and overall survival does not reveal a plateau suggesting that even patients who have not recurred for over 10 years remain at high risk for relapse after treatment with single agent high dose methotrexate. PMID:26507609

  19. Palliative Care in Improving Quality of Life in Patients With High Risk Primary or Recurrent Gynecologic Malignancies


    Cervical Carcinoma; Ovarian Carcinoma; Primary Peritoneal Carcinoma; Recurrent Cervical Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vulvar Carcinoma; Uterine Corpus Cancer; Vulvar Carcinoma; Peritoneal Neoplasms

  20. The Frequency of Recurrence in Primary Hypertensive Intracerebral Hemorrhage

    SA Mousavi


    Full Text Available Background: Primary intracerebral Hemorrhage (PICH is a devasting illness with high early mortality which causes 10 -12 percent of stroke cases. Survivors of PICH are at risk for recurrence of hemorrhage. We wanted to determine the frequency of recurrence of ICH in patients with PICH at Alzahra and Noor hospital Isfahan, Iran. Methods: A descriptive retrospective study was did on the hospital records of patients with a discharge diagnosis of intracerebral hemorrhage to identify the cases. Data were gathered by means of a check list and were analysed by using SPSS statistical software. Results: A total number of 660 cases were identified by computer search. After abstraction, 400 patients with primary hypertensive intracerebral hemorrhage were identified. Widespread distribution of recurrence of ICH were 65 cases which 33 cases of them were men and 32 cases were women. Conclusion: Totally, 16 .25 percent of patients had recurrence which is greater risk of recurrence in comparison to other studies. Key Words: Intracerebral Hemorrhage, hypertension, recurrence of Intracerebral Hemorrhage

  1. Melphalan, Carboplatin, Mannitol, and Sodium Thiosulfate in Treating Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors


    Adult Central Nervous System Germ Cell Tumor; Adult Embryonal Tumor With Multilayered Rosettes, C19MC-Altered; Adult Medulloblastoma; Adult Pineoblastoma; Adult Supratentorial Embryonal Tumor, Not Otherwise Specified; Atypical Teratoid/Rhabdoid Tumor; Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Embryonal Tumor With Multilayered Rosettes, C19MC-Altered; Medulloepithelioma; Ototoxicity; Recurrent Adult Brain Neoplasm; Recurrent Childhood Central Nervous System Embryonal Neoplasm; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Embryonal Tumor, Not Otherwise Specified

  2. Primary cutaneous melanoma of the scalp: Patterns of recurrence.

    Sparks, David S; Read, Tavis; Lonne, Michael; Barbour, Andrew P; Wagels, Michael; Bayley, Gerard J; Smithers, B Mark


    Patients with primary melanoma of the scalp have been reported to have worse disease-related outcomes compared with other anatomical regions. There are few studies in the literature specifically addressing recurrence patterns and treatment outcomes for primary scalp melanoma as a discrete anatomical sub-region. We sought to identify key features adversely influencing disease control and survival and to clarify the role of resection plane, margin, and method of reconstruction in the management of this disease process. A retrospective clinical study of medical records was performed evaluating all patients with primary melanoma of the scalp treated at two hospitals in southeast Queensland between 2004 and 2014. A total of 107 patients were eligible for analysis. There were 46 recurrences in 38 patients in the cohort accounting for a recurrence rate of 35.5%. The local recurrence rate was 15.9% with 12 in-transit metastases after diagnosis. Regional and distant recurrence rates were 12.1% and 15%, respectively. At a median follow up of 30.5 months, disease-free survival was 47% and overall survival was also 47%. On multi-variate analysis, the deeper resection plane (sub-galeal) had a lower disease-free survival rate compared with the supra-galeal resection plane (P = 0.032). Our results support the hypothesis that primary scalp melanoma represents a unique aggressive subcategory with high rates of in-transit disease and poor disease-related and survival outcomes. There is a need for robust prospective comparative studies to address the significance of resection plane in the management of patients with scalp melanoma. © 2016 Wiley Periodicals, Inc.

  3. Recurrence and rejection in liver transplantation for primary sclerosing cholangitis

    Bjarte Fosby; Tom H Karlsen; Espen Melum


    Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease affecting the bile ducts, leading to fibrosis and eventually cirrhosis in most patients. Its etiology is unknown and so far no effective medical therapy is available. Liver transplantation (LTX) is the only curative treatment and at present PSC is the main indication for LTX in the Scandinavian countries. Close to half of the PSC patients experience one or more episodes of acute cellular rejection (ACR) following transplantation and approximately 1/5 of the transplanted patients develop recurrent disease in the graft. In addition, some reports indicate that ACR early after LTX for PSC can influence the risk for recurrent disease. For these important post-transplantation entities affecting PSC patients, we have reviewed the current literature on epidemiology, pathogenesis, treatment and the possible influence of rejection on the risk of recurrent disease in the allograft.

  4. Recurrent rates and risk factors associated with recurrent painful bullous keratopathy after primary phototherapeutic keratectomy

    Kasetsuwan N


    Full Text Available Ngamjit Kasetsuwan, Kanokorn Sakpisuttivanit, Usanee Reinprayoon, Vilavun Puangsricharern Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand Objective: To assess the recurrent rate, mean survival time, and risk factors associated with recurrent painful bullous keratopathy (BK after primary treatment with phototherapeutic keratectomy.Methods: Medical records from 72 patients (72 eyes who had phototherapeutic keratectomy for painful BK were evaluated. Data for sex, age, duration of BK, associated ocular and systemic diseases (hypertension, diabetes mellitus, ischemic heart disease, asthma, dyslipidemia, and rheumatoid arthritis, frequency and degree of pain (grade 1–3, visual acuity, corneal thickness, intraocular pressure, and laser setting were extracted and analyzed.Results: The mean age of the patients was 64.2±11.4 years. The mean preoperative duration of BK was 15.0±11.0 months. Most patients had pseudophakic BK (69.40%. Majority of the cases had grade 3 degree of pain (48.60%. Glaucoma and hypertension were markedly found among these patients (51.40% and 19.40%, respectively. Preoperative mean intraocular pressure and corneal thickness were 13.70±4.95 mmHg and 734.1±83.80 µm, respectively. The mean laser diameter and depth were 8.36±1.22 mm and 38.89±8.81 µm, respectively. Systemic disease was significantly associated with the risk for developing recurrent painful BK (P=0.022, hazard ratio [HR] 1.673, 95% confidence interval [CI] 1.08–2.58. The overall recurrent rate was 51%. The average duration time of recurrent painful BK was 17.3±12.9 months (range 1–50 months. The median survival time before recurrence was 29.0±6.6 months.Conclusion: Systemic disease was found to be the only risk factor significantly associated with the development of recurrent painful BK. Low recurrent rate and long mean survival time showed that phototherapeutic

  5. Combined CNS and pituitary involvement as a primary manifestation of Wegener granulomatosis.

    Spísek, Radek; Kolouchová, Elena; Jensovský, Jirí; Rusina, Robert; Fendrych, Pavel; Plas, Jaroslav; Bartůnková, Jirina


    Wegener granulomatosis (WG) is a systemic vasculitis of small and medium vessels. It predominantly affects the upper and/or lower respiratory airway and kidneys. Its pathogenesis is not fully understood. WG relatively frequently affects the nervous system (in 30-50% according to the different studies). Most frequently, it manifests as necrotizing vasculitis that leads to the peripheral neuropathies or to the cranial nerves palsy. Impairment of the central nervous system (CNS) is less frequent and occurs in 2-8% of patients. Three major pathogenetic mechanisms were described: CNS vasculitis, spreading of granulomas from the adjacent anatomical areas (paranasal cavities, orbit etc.), and new formation of granulomas in brain tissue. This case report describes patients in whom WG manifested in the form of localized skin involvement and combined CNS involvement that included pituitary gland. Atypical presentation of WG impedes and slows down the process of diagnosis and emphasizes the need for collaboration between medical specialists.

  6. Recurrent and Sustained Viral Infections in Primary Immunodeficiencies

    Ruffner, Melanie A.; Sullivan, Kathleen E.; Henrickson, Sarah E.


    Viral infections are commonplace and often innocuous. Nevertheless, within the population of patients with primary immunodeficiencies (PIDDs), viral infections can be the feature that drives a diagnostic evaluation or can be the most significant morbidity for the patient. This review is focused on the viral complications of PIDDs. It will focus on respiratory viruses, the most common type of viral infection in the general population. Children and adults with an increased frequency or severity of respiratory viral infections are often referred for an immunologic evaluation. The classic teaching is to investigate humoral function in people with recurrent sinopulmonary infections, but this is often interpreted to mean recurrent bacterial infections. Recurrent or very severe viral infections may also be a harbinger of a primary immunodeficiency as well. This review will also cover persistent cutaneous viral infections, systemic infections, central nervous system infections, and gastrointestinal infections. In each case, the specific viral infections may drive a diagnostic evaluation that is specific for that type of virus. This review also discusses the management of these infections, which can become problematic in patients with PIDDs. PMID:28674531

  7. Primary Hyperaldosteronism As A Risk Factor For Recurrent Nephrolithiasis

    Ekamol Tantisattamo


    Hyperaldosteronism can cause hypercalciuria, phosphaturia, and hypocitraturia, all of which are risk factors for nephrolithiasis. Additionally, hyperaldosteronism and deoxycorticosterone mediated hypertension have been associated with hypocalcemia and secondary hyperparathyroidism. Our case augments earlier literature suggesting increased risk for nephrolithiasis in patients with hyperaldosteronism and suggests that hyperaldosteronism should be considered as a risk factor for patient with nephrolithiasis. It remains unclear if both primary and secondary hyperaldosteronism increase the relative risk for nephrolithiasis and the role of aldosterone receptor antagonist therapy for recurrent nephrolithiasis associated with hyperaldosteronism.

  8. Recurrence of primary hyperoxaluria: An avoidable catastrophe following kidney transplant

    Madiwale C


    Full Text Available Primary hyperoxaluria is a rare autosomal recessive disease due to deficiency of an oxalate-metabolizing liver enzyme, which results in nephrolithiasis and renal failure. Concomitant liver and kidney transplant is recommended as isolated kidney transplant is inevitably complicated by recurrence of the disease. We present a 25-year-old man with end-stage nephrolithiatic renal disease who underwent bilateral nephrectomy, followed by kidney transplantation. There was progressive worsening of kidney function two weeks post transplant. Review of nephrectomy and transplant kidney biopsy showed abundant calcium oxalate crystals and further workup revealed hyperoxaluria, which was previously unsuspected. Later he developed fever, breathlessness, hemiparesis and died 10 weeks after transplant. Autopsy revealed multi-organ deposits of oxalate crystals as well as widespread zygomycosis. This case emphasizes the need for careful pre-transplant evaluation of patients with renal calculus disease in order to exclude primary hyperoxaluria.

  9. Recurrent cardiac metastasis of primary femoral osteosarcoma: a case report.

    Iyigun, Taner; Ciloglu, Ufuk; Ariturk, Cem; Civelek, Ali; Tosun, Remzi


    A 17-year-old female patient with a history of surgery for primary femoral and metastatic lung osteosarcoma was admitted to our clinic with palpitations. Upon evaluation, a metastatic osteosarcoma in the left ventricle was diagnosed. Based on the collaborative decision of the oncology and cardiovascular surgery clinics, surgery was performed and the patient was discharged without any problems. According to the recommendation of the oncology clinic, chemotherapy was postponed for 6 months after surgery. Five months postoperatively, however, she had a recurrence with 2 tumors. Based on the collaborative decision, chemotherapy was initiated and in 2 months the size of the recurrent tumors had diminished. The patient is still under the care of the oncology and cardiovascular surgery clinics and continuing her chemotherapy regimen. Osteosarcomas have a high mortality. Metastatic tumors of the heart are not common. The location of the metastasis and the characteristics of the primary tumor determine the treatment modality. In some previously published reports, various treatment choices have been described. In the present case report, we present a rare case with metastatic cardiac osteosarcoma.

  10. Primary CNS Nonamyloidogenic Light Chain Deposition Disease: Case Report and Brief Review.

    Mercado, Juan Jose; Markert, James M; Meador, William; Chapman, Philip; Perry, Arie; Hackney, James R


    The true incidence of light chain deposition disease (LCDD) restricted to the central nervous system (CNS) is unknown. To our knowledge only 7 cases of LCDD restricted to the brain have been previously reported. We herein describe an unusual example. A 44-year-old man presented with a history of ischemic retinopathy in 2004 and left lower extremity hypoesthesia in 2007 that progressed gradually to left-sided weakness and numbness in the 2 years prior to his hospitalization in 2015. A stereotactic brain biopsy was performed, displaying nonspecific hyaline deposits of amorphous "amyloid-like" material involving deep brain white matter and vessels. These were Congo red negative and were accompanied by a sparse lymphoplasmacytic infiltrate. Plasma cells demonstrated kappa light chain class restriction by chromogenic in situ hybridization (CISH). There was patchy reactivity with kappa immunohistochemistry in the amorphous deposits. A diagnosis of light chain deposition disease was made. Subsequent systemic myeloma and lymphoma workups were negative. Previously reported cases have included men and women, spanning the ages of 19 and 72 years, often presenting with hemiparesis, hypoesthesia, or seizures. Deposits have been reported in the cerebrum and cerebellum. T2/FLAIR (fluid attenuation inversion recovery) changes are usual, but lesions may or may not produce contrast enhancement. The light chain deposition may be of kappa or lambda class. Most lesions have been accompanied by local lymphoid and/or plasma cell infiltrates exhibiting light chain restriction of the same class as the deposits. In summary, LCDD limited to the CNS is a rare lesion consisting of deposition of amyloid-like, but Congo red-negative monotypic light chain usually produced by local lymphoplasmacytic infiltrates.

  11. Functional Endoscopic Sinus Surgery as a primary modality of treatment for primary and recurrent nasal polyposis.

    Gohar, Mohammad Shahid; Niazi, Saleem Asif; Niazi, Sohail Baber


    To describe the efficacy of Functional Endoscopic Sinus Surgery(FESS) in our set up in comparison with other published studies to treat primary and recurrent nasal polyposis. This descriptive study was conducted in 02 years at Ear Nose Throat Department Combined Military Hospital (CMH) Multan from October 2013 to October 2015. Convenient sample comprising 116 patients of both sexes of age group from 18 to 60 years were selected from ENT Out Patient Department, with documented diagnosis of nasal polyposis that underwent functional endoscopic sinus surgery. Out of 116 patients, 15 (12.9%) had recurrent nasal polyposis while 101 (87.1%) had primary nasal polyposis. Patients were assessed clinically. Preoperative nasal endoscopy and CT scan of nose and paranasal sinuses were performed in every patient to assess the extent of disease and evaluate the surgical anatomy. Patients were followed up 03 monthly, 06 monthly and after 01 year. Clinical signs of nasal polyposis were evaluated by nasal endoscopy at each follow up visit. There were 116 patients with documented diagnosis of nasal polyposis. Among these, 75 (64.7%) were male and 41 (35.3%) were female patients. Mean age of presentation in males was 39.1 years and that of females was 36.7 years. Only 15 patients (12.9%) developed recurrent disease within a year. Functional endoscopic sinus surgery is preferred as a primary treatment modality for primary and recurrent nasal polyposis. Mucosal polyps can be carefully debrided, the natural ostia enlarged, the ethmoid sinuses are unroofed, and sphenoid sinuses are opened in nasal cavity and sinus nasal mucosa is mostly preserved due to excellent visualization and surgical technique. Improvement in symptoms with minimal chance of recurrence may be expected in more than 90% patients.

  12. Recurrent primary hyperparathyroidism due to Type 1 parathyromatosis.

    Jain, Monica; Krasne, David L; Singer, Frederick R; Giuliano, Armando E


    Parathyromatosis is a rare condition consisting of multiple nodules of benign hyperfunctioning parathyroid tissue scattered throughout the neck and superior mediastinum. As a potential cause of recurrent or persistent hyperparathyroidism, parathyromatosis is a challenging condition to diagnose and treat. The optimal evaluation and management of patients with parathyromatosis is not well established. The reported case involves a patient who was initially diagnosed with primary hyperparathyroidism. The diagnosis of Type 1 parathyromatosis was made after the patient developed recurrent hyperparathyroidism with hypercalcemia and osteoporosis 17 years after the initial operation and underwent two additional operations. The majority of parathyromatosis cases are diagnosed in the setting of secondary hyperparathyroidism. Consensus regarding the preoperative diagnosis and evaluation is lacking due to the paucity of cases of this rare clinical entity. Management involves complete surgical extirpation of all identifiable rests of parathyroid tissue. Intra-operative parathyroid hormone level monitoring and frozen section examination are excellent tools that could increase the rates of initial operative success. Despite this, long-term disease remission is rare, and medical therapy, including calcimimetics and bisphosphonates, may be required for postoperative or non-operative management.

  13. Recurrence of primary sclerosing cholangitis in pediatric liver transplant recipients.

    Venkat, Veena L; Ranganathan, Sarangarajan; Mazariegos, George V; Sun, Qing; Sindhi, Rakesh


    There is little detailed clinical information on recurrent primary sclerosing cholangitis (rPSC) after liver transplantation in children. Our purpose was to describe the characteristics of children who had experienced rPSC after liver transplantation so that we could identify potential risk factors for recurrence. Clinical information for pediatric patients undergoing transplantation for primary sclerosing cholangitis (PSC) was retrospectively reviewed, and variables related to the pretransplant diagnosis of PSC and posttransplant variables were abstracted. The studied variables included the following: cytomegalovirus/Epstein-Barr virus status, early/late rejection, induction regimen, immunosuppression in the first year, steroid-resistant rejection, diagnosis of inflammatory bowel disease, and human leukocyte antigen markers commonly associated with PSC. A diagnosis of rPSC was made on the basis of radiographic features, histology, or both. Twelve patients underwent liver transplantation for PSC between 1993 and 2012. Patients received tacrolimus for maintenance immunosuppression after induction with steroids (n = 6) or thymoglobulin (n = 6). Three patients were diagnosed with rPSC 44, 60, and 62 months after transplantation. A fourth patient underwent retransplantation for graft failure with features of both hepatic artery stenosis and rPSC. This patient had distinct histological features of rPSC in the second graft. Three of the 4 patients were 7 years old or younger at the diagnosis of PSC. The patient and graft survival rates were similar for the steroid and thymoglobulin groups. All 4 children with rPSC received steroid-free thymoglobulin induction. In conclusion, our observation of an association between thymoglobulin, and age less than 10 years at the diagnosis of PSC, and rPSC adds to the existing suggestion of a link between the immune environment and the pathogenesis of rPSC. Defining the natural history of rPSC and searching for the etiology and

  14. Burden of malignancy after a primary skin cancer: recurrence, multiple skin cancers and second primary cancers.

    Krueger, Hans; Williams, Dan


    The current paper summarizes relevant recent research on the high risk of recurrence, multiple skin cancers and second primary cancers in the growing number of people with a history of skin cancer; the ultimate purpose is to better assess the burden of malignancy following skin cancer. A number of challenges exist in identifying and tracking both melanoma and non-melanoma skin cancer (NMSC) cases. Most jurisdictions do not routinely track NMSC cases and, even if they do, it is customary to only include the first diagnosis. There are variable rules for counting multiple melanoma cancers, and recurrences are not considered for either major type of skin cancer. Applying insights from recent studies of this issue to Canadian cancer statistics would increase reported diagnoses of NMSC by about 26% and melanoma by 10% in this country. This approach to a fuller assessment of the burden of skin cancers has been called a "diagnosis-based incidence approach" as compared with a "patient-based incidence approach". A further issue that is not usually taken into account when assessing the burden of skin cancers is the 20% to 30% elevated risk of noncutaneous second primary cancers following a primary skin tumour. In summary, individuals with skin cancer are subject to a high risk of recurrence, multiple skin cancers and second primary cancers. This burden should be a special concern in the large and growing pool of individuals with a history of skin cancer, as well as among prevention planners.

  15. Mast cells and angiogenesis in primary and recurrent pterygia

    Fatma Hüsniye DİLEK


    Full Text Available Pterygium is a common benign lesion of limbus but the pathogenesis are not completely understood. Pterygia have a chronic inflammatory cellular infiltrate and a rich vasculature. Mast cells are a heterogeneous group of multifunctional tissue-resident cells. It has been suggested that mast cells and their products may be responsible for the formation of new blood vessels. We investigated the number and phenotype of mast cells and neovascularization in pterygia specimens and compared with those in normal conjunctival specimensPterygia tissues were obtained during excisional surgery from 32 eyes of 32 consecutive patients. Seventeen of all cases were recurrent pterygia. Superior bulbar conjunctival tissue from the same eye was also sampled as control tissues. The tissue sections were stained with routine hematoxyline-eosin and toluidine blue stain for mast cells. For immunohistochemical studies anti-factor VIII-related antigen, monoclonal anti human mast cell tryptase and chymase were used as an endothelial and mast cell marker.The mean number of mast cells in pterygia was significantly higher than that in the normal conjunctival tissue and microvessel counts was significantly higher than the counts of the controls in both primary and recurrent pterygia. There was no correlation between microvessel numbers and mast cell numbers. There was no phenotypic difference between the mast cells in the ptergyia and those in the normal conjunctival tissues.This study confirms that mast cells are prominent in pterygia and our results suggest that mast cells and angiogenesis are independent factors in the genesis and progress of ptergyium.

  16. Treatment Options for Primary Refractory/Recurrent Hodgkin Lymphoma in Children and Adolescents

    ... Primary Refractory/Recurrent Hodgkin Lymphoma in Children and Adolescents Primary refractory Hodgkin lymphoma is lymphoma that continues ... treated with an adult treatment regimen . Children and adolescents may have treatment-related side effects that appear ...

  17. Distribution and Prevalence of Locoregional Recurrence after Video-Assisted Thoracoscopic Surgery for Primary Lung Cancer.

    Haruki, Tomohiro; Miwa, Ken; Araki, Kunio; Taniguchi, Yuji; Nakamura, Hiroshige


    Background The aim of this study is to evaluate cases with locoregional recurrence after video-assisted thoracoscopic surgery (VATS) for primary lung cancer. Methods We reviewed 248 patients with primary lung cancer who underwent lobectomy or segmentectomy with mediastinal lymph node dissection by VATS between January 2005 and December 2011. Locoregional recurrence is defined as per its occurrence in (1) bronchial stump or lung parenchymal cut end, (2) ipsilateral pleura, and (3) ipsilateral hilar and mediastinal lymph nodes, and we analyzed recurrence rate and significant associated factors for locoregional recurrence by logistic regression analysis. Results There were 47 cases of postoperative recurrence, which consisted of 26 distant, 6 locoregional and distant, and 15 locoregional recurrences. The locoregional recurrence rate was 6.0%. Of the 15 locoregional recurrence cases, there were two cases of bronchial stump and lung parenchyma cut end (0.4%), five cases of ipsilateral pleura (2.0%), and eight cases of ipsilateral hilar and mediastinal lymph nodes (3.2%). Pleural and lymphovascular invasion and advanced stages were significant associated factors in univariate analysis. Multivariate analysis revealed that advanced stages were only a significant associated factor for locoregional recurrence (p recurrence rates of our surgical treatments for primary lung cancer by VATS might be acceptable, we should explore more effective modalities against pathologically proven local advanced lung cancer for preventing not only distant but also locoregional recurrences. Georg Thieme Verlag KG Stuttgart · New York.

  18. Role of Expression of Inflammatory Mediators in Primary and Recurrent Lumbar Disc Herniation

    Dagistan, Yasar; Cukur, Selma; Dagistan, Emine; Gezici, Ali Riza


    Objective To assess role of some inflammatory mediators in patients with primary and recurrent lumbar disc herniation. Expression of IL-6, transforming growth factor (TGF)-1, insulin-like growth factor (IGF)-1, and Bcl-2-associated X protein (BAX) have been shown to be more intense in the primary group than the recurrent goup, but this mediators may be important aspects prognostic. Methods 19 patients underwent primary and revision operations between June 1, 2009 and June 1, 2014, and they were included in this study. The 19 patients’ intervertebral disc specimens obtained from the primary procedures and reoperations were evaluated. Expression of IL-6, TGF-1, IGF-1, and BAX were examined immunohistochemically in the 38 biopsy tissues obtained from the primary and recurrent herniated intervertebral discs during the operation. Results For IL-6 expression in the intervertebral disc specimens, there was no difference between the groups. The immunohistochemical study showed that the intervertebral disc specimens in the primary group were stained intensely by TGF-1 compared with the recurrent group. Expression of IGF-1 in the primary group was found moderate. In contrast, in the recurrent group of patients was mild expression of IGF-1. The primary group intervertebral disc specimens were stained moderately by BAX compared with the recurrent group. Conclusion The results of our prognostic evaluation of patients in the recurrent group who were operated due to disc herniation suggest that mediators may be important parameters. PMID:28061491

  19. Characteristics and outcome of patients with primary CNS lymphoma in a "real-life" setting compared to a clinical trial.

    Zeremski, Vanja; Koehler, Michael; Fischer, Thomas; Schalk, Enrico


    We aimed to compare the characteristics and outcome of patients treated within the multi-centre German Primary CNS Lymphoma Study Group 1 trial (G-PCNSL-SG-1; TRIAL group) and patients treated outside this clinical trial ("real-life" setting, R-LIFE group). Therefore, we conducted a retrospective single-centre study in order to analyse all patients with newly diagnosed primary CNS lymphoma (PCNSL) treated consecutively in our institution between November 2000 and June 2015. Altogether, 86 patients were analysed (median 68 years). Twenty patients were treated within (TRIAL) and 66 patients outside the clinical trial (R-LIFE), respectively. The majority (n = 75; 87 %) received high-dose methotrexate as the first-line treatment. Thirty-eight of 66 patients (57.6 %) responded to the first-line therapy. The R-LIFE patients were older (median age 70 vs. 62 years; p = 0.005) and had more frequently a worse performance status (ECOG score 2-4: 59.1 vs. 20.0 %; p = 0.004; median Karnofsky index 70 vs. 80 %; p = 0.003) and less frequently a low prognostic score (IELSG score 0-1: 19.7 vs. 45.0 %; p = 0.038), than the TRIAL patients. Median overall survial (OS) was shorter for the R-LIFE patients (9.3 months [95 % CI 1.9-16.7] vs. 33.4 months [95 % CI 17.6-49.2]; p = 0.065). Median progression-free survival (PFS) was significantly inferior for the R-LIFE patients (3.4 months [95 % CI 2.4-4.4] vs. 24.8 months [95 % CI 4.6-45.0]; p = 0.037). Our data indicate that the outcome of PCNSL patients treated outside, but about analogous to the G-PCNSL-SG-1 trial, was poor. This is likely explained by more unfavourable prognostic factors in patients being treated off trial.

  20. Local melanoma recurrences in the scar after limited surgery for primary tumor

    Drzewiecki, K T; Andersson, A P


    The clinical and histologic records of 46 consecutive patients were reviewed who during the period 1980-1993 had recurrence from melanoma in the scar after limited surgery for a skin tumor. They constituted about 50% of all patients admitted with local recurrence from melanoma during this period....... At reexamination of the primary tumors, 16 were found to be malignant melanomas and 9 were nevi (four atypical and five benign). Twenty-one were missing, 11 of which had never been set for histologic examination. The median thickness of nine measurable melanomas was 0.66 mm. The recurrences in scar consisted of 34...... recurrences in the form of a new primary in a scar following limited surgery supports the theory of limited field change around a primary melanoma. Furthermore, limited procedures for primary melanoma, if followed by a recurrence in the scar, worsen the prognosis....

  1. A Case of Primary Bacterial Pericarditis with Recurrent Cardiac Tamponade.

    Yoshizane, Takashi; Yamamoto, Takeshi; Hayashi, Hiroshi; Kitamura, Mitsunobu; Miyachi, Hideki; Hosokawa, Yusuke; Akutsu, Koichi; Shimizu, Wataru


    Cardiac tamponade is an important and potentially lethal complication of acute pericarditis. However, recurrence of cardiac tamponade is rare when it is treated appropriately. We present a 49-year-old man with bacterial pericarditis and recurrent cardiac tamponade, which was caused by the rupture of an upper part of the left atrium (LA). According to the autopsy findings, bacteremia from Staphylococcus aureus developed on a substrate of poorly controlled diabetes mellitus and spread to the pericardium via the blood. Subsequently, tissue necrosis developed from the pulmonary trunk and aorta to the LA, leading to recurrence of cardiac rupture and cardiac tamponade.

  2. DNA ploidy of primary and recurrent irradiated laryngeal tumors

    Struikmans, H; Hordijk, GJ; Kal, HB


    Purpose: Radiosensitivity of diploid laryngeal cancers, as compared with that of aneuploid ones, appears to be increased. However, no conclusive data exist. If a causal relationship exists, then recurrent laryngeal cancer after irradiation should predominantly be characterized by aneuploidy. Patient

  3. Risk factors for recurrence of primary spontaneous pneumothorax after thoracoscopic surgery.

    Huang, Haibo; Ji, Hua; Tian, Hui


    Primary spontaneous pneumothorax recurs at a certain rate after thoracoscopic surgery, and risk factors for that recurrence are in question. The medical records of 248 patients with primary spontaneous pneumothorax who were followed for more than 2 years after thoracoscopic surgery were reviewed and retrospectively analyzed. Univariate and multivariate binary logistic regression analysis were used to identify possible risk factors. Twelve patients experienced the recurrence of primary spontaneous pneumothorax. Patients who experienced the recurrence of primary spontaneous pneumothorax were younger than patients who experienced no recurrence. A larger proportion of the patients who experienced recurrence did not undergo pleurodesis. The variables age, height, weight, body mass index, duration of air leakage, and pleurodesis (performed or not) with a p value less than 0.2 in univariate analysis were entered in multivariate analysis. A younger age and not undergoing pleurodesis were associated with a higher risk of postoperative ipsilateral recurrence of primary spontaneous pneumothorax. Not undergoing pleurodesis and a younger age are possible risk factors for recurrence of primary spontaneous pneumothorax after thoracoscopic surgery. Thoracic surgeons should pay more attention to pleurodesis, especially in younger patients.

  4. Efficacy of radiofrequency ablation for initial recurrent hepatocellular carcinoma after curative treatment: Comparison with primary cases

    Fukuhara, Takayuki; Aikata, Hiroshi, E-mail:; Hyogo, Hideyuki; Honda, Yohji; Morio, Kei; Morio, Reona; Hatooka, Masahiro; Kobayashi, Tomoki; Naeshiro, Noriaki; Kawaoka, Tomokazu; Tsuge, Masataka; Hiramatsu, Akira; Imamura, Michio; Kawakami, Yoshiiku; Chayama, Kazuaki


    Highlights: • We compared clinical and outcome factors after RFA treatment between primary HCC and recurrent HCC. • Local tumor control and OS are similar, but DFS was significantly shorter in the recurrent group. • RFA is an effective and safe treatment option for initial recurrent small HCC. - Abstract: Objective: To determine the efficacy of radiofrequency ablation (RFA) for initial recurrence of small hepatocellular carcinoma (HCC; ≤3 nodules, each nodule ≤3 cm in diameter) after curative treatment and identify prognostic factors affecting therapeutic outcome, we compared clinical and outcome factors between patients with primary HCC and those with initial recurrent HCC who underwent RFA. Methods: In this retrospective cohort study, 211 HCC patients who underwent RFA were enrolled and comprised two groups: primary group (n = 139) and initial recurrent group (n = 72). We compared local tumor progression, overall survival (OS), disease-free survival (DFS), and RFA safety between the groups. Results: Median follow-up was 53 months. Local tumor progression rate was 5.8% in the primary group and 4.2% in the recurrent group. OS rates at 5 years and 10 years were 63.2% and 25.5% in the primary group and 54.5% and 33.4% in the recurrent group, respectively. Corresponding DFS rates were 30.7% and 14.6% and 19.2% and 11.0%. DFS was significantly shorter in the recurrent group (hazard ratio [HR] = 1.81; 95% confidence interval [CI], 1.27–2.57; P = 0.001). In the recurrent group, time from primary HCC development to recurrence was a determinant of OS (≤2 years; HR = 3.42; 95% CI, 1.52–7.72; P = 0.003). Conclusion: Although local tumor control and OS were similar between the groups, the recurrent group had shorter DFS than the primary group. Time from primary HCC development to recurrence was a prognostic factor for recurrence of HCC.

  5. Recurrent parotitis as a first manifestation in a child with primary Sjogren's syndrome.

    Alp, H; Orbak, Z; Erdogan, T; Karabag, K; Gursan, N


    Recurrent parotitis is an acute, severe inflammation of one or both parotid glands, the major salivary glands in young children. We report the case of a seven-year old boy with Primary Sjogrens syndrome (PSS) who presented with 15 episodes of painful recurrent bilateral swellings of the parotid glands over a four-year period.

  6. Late-onset peritoneal recurrence of advanced gastric cancer 20 years after primary resection

    Mohri Yasuhiko


    Full Text Available Abstract Late onset of peritoneal recurrence of gastric cancer more than 10 years after surgery is extremely rare, and only three cases have been reported. We present the case of a 61-year-old man who was diagnosed finally with peritoneal recurrence of gastric cancer 20 years after primary curative resection. As a result of small-bowel obstruction caused by peritoneal recurrence, diverting ileostomy with partial ileal resection was performed. The resected specimen revealed tubular adenocarcinoma that resembled the primary gastric cancer. The clinical course after the second operation was unfavorable and systemic chemotherapy had no effect. He died at 62 years of age, 21 years and 7 months after initial gastrectomy. Immunohistochemical analysis using antibodies against proliferating cell nuclear antigen (PCNA, Ki-67, and p53 was performed to investigate the phenotype of primary and recurrence cancer. Protein expression of proliferation markers such as PCNA and Ki-67 was down-regulated, but p53 was overexpressed at the site of recurrence. These data suggest that late peritoneal recurrence has a low proliferation rate and is resistant to chemoradiotherapy. In conclusion, we present late onset of peritoneal recurrence of gastric cancer more than 20 years after primary surgery, and speculate on the mechanism of late-onset recurrence in our case.

  7. Clinical relevance of recurrence of primary biliary cirrhosis after liver transplantation

    Haagsma, EB


    Review of the literature shows that recurrence of primary biliary cirrhosis occurs in about 10% of patients in the first few years after liver transplantation. The cumulative risk is expected to increase in time, The rate of recurrent disease may be affected by the immunosuppression used. Weaning fr

  8. Management of locally advanced primary and recurrent rectal cancer

    J.H.W. de Wilt (Johannes); M. Vermaas (Maarten); F.T.J. Ferenschild (Floris); C. Verhoef (Kees)


    textabstractTreatment for patients with locally advanced and recurrent rectal cancer differs significantly from patients with rectal cancer restricted to the mesorectum. Adequate preoperative imaging of the pelvis is therefore important to identify those patients who are candidates for multimodality

  9. Staging Primary CNS Lymphoma

    ... reflexes work. This may also be called a neuro exam or a neurologic exam. Slit-lamp eye ... Websites POLICIES Accessibility Comment Policy Disclaimer FOIA Privacy & Security Reuse & Copyright Syndication Services Website Linking U.S. Department ...

  10. Radiation therapy in recurrence of carcinoma of the uterine cervix after primary surgery

    Kim, Jin Hee; Kim, Ok Bae [College of Medicine, Keimyung Univ., Daegu (Korea, Republic of)


    The purpose of this study was to evaluate treatment results in terms of the survival and failure patterns subsequent to radiation therapy in recurrent cervical cancer, following primary surgery. Between January 1990 and December 1999, 27 patients, with recurrent cervical cancer following primary surgery, were subsequently treated with radiation in the Department of Radiation Oncology, at the Keimyung University Dongsan Medical Center. Their median age was 48, ranging from 31 to 70 years old. With regard to the initial FIGO stage on presentation, 20 and 7 patients were stages I and II, respectively. Twenty three patients had squamous ceH carcinomas and 4 had adenocarcinomas. The time interval from the primary surgery to the recurrence ranged from 2 to 90 months with a median of 29 months. The recurrent sites were the vaginal cuff alone, the pelvic cavity and combined recurrence in 14, 9 and 4 patients, respectively. Radiation was performed, with external and vaginal intracavitary radiation in 13 patients, external radiation alone in 13 and vaginal intracavitary radiation alone in another one. The median follow-up period was 55 months, ranging from 6 to 128 months. The five year disease free survival (5y DFS) and five year overall survival (5y OS) rates were 68.2 and 71.9%, respectively. There was a marginal statistically significant difference in the 5y DFS in relation to the recurrent site (5y DFS, 85.7% in vaginal cuff recurrence alone, 53.3% in pelvic cavity recurrence, p=0.09). There was no difference in the survival according to the time interval between the primary surgery and a recurrence. There was only a 7% local failure rate in the patients with a vaginal cuff recurrence. The major failure patterns were local failure in the patients with pelvic cavity recurrence, and distant failure in the patients with a combined recurrence. There were no complications above grade 3 after the radiation therapy. Radiation therapy was safe and effective treatment for a

  11. Primary hyperparathyroidism presenting as recurrent acute pancreatitis: A case report and review of literature

    Raiz A Misgar


    Full Text Available The association between pancreatitis and primary hyperparathyroidism (PHPT is controversial. We report a 32-year-old man who presented with recurrent episodes of acute pancreatitis. Primary hyperparathyroidism was diagnosed after the fourth episode of pancreatitis. He had no additional risk factors for pancreatitis. Eighteen months after successful parathyroid surgery, there has been no recurrence of abdominal pain and his serum calcium is within the normal range.

  12. Expression of cell cycle-related gene products in different forms of primary versus recurrent PVNS.

    Weckauf, Helgard; Helmchen, Birgit; Hinz, Ulf; Meyer-Scholten, Carola; Aulmann, Sebastian; Otto, Herwart F; Berger, Irina


    Expression patterns of cell cycle regulating gene products and Ki-67 in proliferating synovial cells of primary and recurrent pigmented villonodular synovitis (PVNS) in localized and diffuse lesions were examined by immunohistochemistry. Alterations of cell cycle-related proteins were seen in 98.7% of analyzed lesions. Both RB- and p53 pathways play a role in cell cycle dysregulation in PVNS. The RB pathway was more frequently altered in primary disease, while alterations of the p53 pathway seemed to be more important in recurrent lesions, regardless of the histomorphological type of disease. Ki-67 proliferation rate was elevated in recurrent tumors. Copyright 2004 Elsevier Ireland Ltd.

  13. A Review of Management of Clostridium difficile Infection: Primary and Recurrence

    Yasmeen Vincent


    Full Text Available Clostridium difficile infection (CDI is a potentially fatal illness, especially in the elderly and hospitalized individuals. The recurrence and rates of CDI are increasing. In addition, some cases of CDI are refractory to the currently available antibiotics. The search for improved modalities for the management of primary and recurrent CDI is underway. This review discusses the current antibiotics, fecal microbiota transplantation (FMT and other options such as immunotherapy and administration of non-toxigenic Clostridium difficile (CD for the management of both primary and recurrent CDI.

  14. A Review of Management of Clostridium difficile Infection: Primary and Recurrence.

    Vincent, Yasmeen; Manji, Arif; Gregory-Miller, Kathleen; Lee, Christine


    Clostridium difficile infection (CDI) is a potentially fatal illness, especially in the elderly and hospitalized individuals. The recurrence and rates of CDI are increasing. In addition, some cases of CDI are refractory to the currently available antibiotics. The search for improved modalities for the management of primary and recurrent CDI is underway. This review discusses the current antibiotics, fecal microbiota transplantation (FMT) and other options such as immunotherapy and administration of non-toxigenic Clostridium difficile (CD) for the management of both primary and recurrent CDI.

  15. Aggressive Recurrence of Primary Hepatic Epithelioid Haemangioendothelioma after Liver Transplantation

    Qusay A. Abdoh


    Full Text Available HEHE is a rare neoplasm of vascular origin that occurs in the liver; UNOS reported a favorable outcome after liver transplantation in 110 patients with 1-year and 5-year survival of 80% and 64%. Case Report. A 40-year-old lady presented with a three-month history of right upper abdominal pain with nausea, vomiting, and significant loss of weight associated with scleral icterus and progressive abdominal distension. Examination revealed jaundice, hepatomegaly, and ascites. Serum bilirubin was 26.5 mg/dL and ALP was 552 CT. Abdomen and pelvis showed diffuse infiltrative neoplastic process of the liver with a mass effect and stretching of the hepatic and portal veins, in addition to bile duct dilatation. Viral hepatitis markers were negative and serum alpha fetoprotein was within reference range. Liver biopsy was consistent with HEHE, with positive endothelial markers (CD31, CD34, and factor VIII-related antigen. She underwent living related liver transplantation on June 2013 and was discharged after 20 days with normal liver enzymes. Four months later, she presented with diffuse disease recurrence. Liver biopsy confirmed disease recurrence; she received supportive treatment and unfortunately she died 2 weeks later. Conclusion. HEHE can have rapid and aggressive recurrence after liver transplantation.

  16. Recurrent Primary Fibromatosis in the Breast: A Case Report

    Lim, Soo Jin; Kang, Young Hae; Lee, Ju Won; Kim, Youn Jeong [Dept. of Radiology, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of); Kim, Lucia [Dept. of Pathology, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of); Cho, Young Up [Dept. of Surgery, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of)


    Fibromatosis is a rare benign tumor that presents predominantly as a unilateral, painless, palpable, and firm to hard mass which may be accompanied by skin dimpling and nipple retraction. It is characterized as an infiltrating fibroblastic and myofibroblastic proliferation that can behave in a locally aggressive fashion if incompletely excised. However, it is not known to metastasize. We report a case of a 39-year-old female with recurrent fibromatosis in the breast. Initially, the mass was detected by a screening mammography. It appeared as an oval mass and recurred twice after surgical excision over a 36-month period with a more suspicious appearance.

  17. O6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry as a predictor of resistance to temozolomide in primary CNS lymphoma.

    Jiang, Xiaoyin; Reardon, David A; Desjardins, Annick; Vredenburgh, James J; Quinn, Jennifer A; Austin, Alan D; Herndon, James E; McLendon, Roger E; Friedman, Henry S


    Temozolomide, an alkylating agent, has shown promise in treating primary central nervous system lymphoma (PCNSL). The enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) repairs alkylating damage, such as that induced by temozolomide. We hypothesized that MGMT immunohistochemistry would predict resistance to temozolomide in PCNSL. A retrospective study of newly-diagnosed and recurrent PCNSL patients treated at our institution was conducted to study the predictive value of MGMT immunohistochemistry for response to temozolomide. 20 patients who were treated with temozolomide as a single agent were identified during the study time period. 6/20 patients demonstrated a response, corresponding to an objective response rate of 30 % (95 % CI 8-52). Five patients with low MGMT level (temozolomide. Only one of 10 patients (10 %) with high MGMT level (≥30 %) exhibited a response to temozolomide. Small sample numbers precluded formal statistical comparisons. Two patients with complete response remain alive without progressive disease 6.7 and 7.2 years after temozolomide initiation. Immunohistochemistry can be performed on small biopsies to selectively assess MGMT status in tumor versus surrounding inflammation. MGMT analysis by immunohistochemistry may predict response to temozolomide in PCNSL and should be prospectively investigated.

  18. Atypical chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroids (CLIPPERS), primary angiitis of the CNS mimicking CLIPPERS or overlap syndrome? A case report.

    Buttmann, Mathias; Metz, Imke; Brecht, Isabel; Brück, Wolfgang; Warmuth-Metz, Monika


    A novel type of encephalomyelitis was first described as chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in 2010 and few additional patients were reported since then. Partially due to its unknown aetiology and a lack of pathognomonic features some have suggested that CLIPPERS may not represent a distinct disease, but rather a syndrome with different underlying aetiologies. Here we report a 49-year-old German female who presented with a number of clinical and paraclinical features described as typical for CLIPPERS, while additionally showing symptoms and findings compatible with primary angiitis of the CNS (PACNS). This case may establish a previously unnoted link between two poorly understood autoimmune conditions of the CNS.

  19. Analysis of diferentially expressed protein from primary and recurrent ovarian cancer serum

    Yuan Wang; Jin-Jin Yu; Ting Zhu; Ling Xu; Ming Xu; Yu-Zheng Huang; Hong Pu; Chun-Qing Yu


    ABSTRACT Objective:To study the value of the differentially expressed proteins from primary and recurrent ovarian cancer serum for early diagnosis of primary and recurrent ovarian cancer.Methods:WCX kit(BrukerDaltonicsGraBH) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS) technology were used to detect serum samples from49 patients with primary ovarian cancer and21 patients with recurrent disease.Results:In the mass range(Mr) from1000 to12000Da, eight differentially expressed protein peaks were screened from primary ovarian cancer serum.Among them, four protein peaks withMr1457,1857,2202, 7761 were lowly expressed and the others withMr2946,5333,5859,5901 were highly expressed. Ten diferentially expressed protein peaks were screened from recurrent ovarian cancer serum. Among them,1944,1980,2080,2661,2993,4450,4659,5359Da protein expressions were increased significantly, and1897,7868Da protein expressions were decreased significantly.The pattern of primary ovarian cancer was applied to8 early-stage ovarian cancer serum samples, and7 serum samples were successfully predicted with the accuracy of87.5%.The pattern of recurrent ovarian cancer was applied to9 without pelvic or abdominal mass recurrent ovarian cancer serum samples, and8 serum samples were successfully predicted with the accuracy of 88.9%.Conclusions:Combination ofMALDI-TOF-MS andWCX kit technology can directly screen the diferrential expressed protein from primary and recurrent ovarian cancer serum.They have clinical significance for enhancement of sensitivity and specificity of ovarian cancer diagnosis.

  20. The Effects of Combined Hepatectomy and Immunochemotherapy on Postoperative Recurrence of Primary Liver Cancer

    ZHOUWeiping; WUMengchao; 等


    Ojbective To Study the effects of combined hepatectomy and immunochemotherapy on postoperative recurrence of primary liver cancer.Methods 121 caes were divided into four groups:operation only(OP group);combined operation and chemotherapy(OC group);combined operation and immunotherapy(OI group);combined operation and immunochemotherapy(OIC group).Chemotherapy was performed through hepatic arter or port vein,and the immunotherapy was used with LAK cell IL-2 and IFN-γ。Results Three-yeau recurrence rate in the four groups was 76.7%,55.6%,45.2% and 36.4%,respectively.The recurrence rate of OI group and OIC group was significantly lower than that of OP group.Conclusion Combined operation and immunochemotherapy in useful in preventing postoperative recurrence of primary liver cancer.

  1. A genome-wide allelotype study of primary and corresponding recurrent glioblastoma multiforme in one patient

    胡杰; 江澄川; 吴浩强; 彭颂先; 唐婉君; 陈商群


    @@Glioblastoma multiforme (GBM) is the most common type of primary malignant brain tumor. Although comprehensive therapeutic measures are available, recurrence is very frequent and the prognosis of GBM remains dismal. To date, little is known about the molecular pathogenesis associated with GBM recurrence. According to Knudson ' s two-hit hypothesis of tumor suppressor gene (TSG) inactivation,1 deletion of a chromosomal region, as revealed by loss of heterozygosity (LOH), is often indicative of the presence of a potential TSG. Allelotype studies involving a comprehensive LOH analysis of the whole genome can provide more detailed and thorough information for detecting genetic anomalies than traditional LOH analysis. The present study is designed to conduct a genome-wide allelotype analysis of one patient ' s primary and corresponding recurrent GBM tumors in an effort to reveal molecular genetic alterations associated with the recurrence of this malignancy.

  2. [Predictive factors for locally recurrent rectal cancer after primary curative surgery].

    Gao, Haoji; Zhang, Tao; Zhao, Ren


    Local recurrence is a major clinical challenge after primary rectal cancer surgery. Although there is a possibility that R0 resection can be achieved, the outcome is still not favorable due to the low R0 resection rate and complexity of the surgery. Therefore prevention has a higher priority over treatment afterwards. As TME principle is accepted worldwide, the local recurrence rate has been reduced dramatically. And there are other factors associated with local recurrence including CRM, operation type, staging and PNI. Proper chemoradiotherapy may reduce the risk, however benefit always comes with side effect, therefore risk stratification is important.

  3. Carboplatin and Gemcitabine Hydrochloride With or Without ATR Kinase Inhibitor VX-970 in Treating Patients With Recurrent and Metastatic Ovarian, Primary Peritoneal, or Fallopian Tube Cancer


    High Grade Ovarian Serous Adenocarcinoma; Ovarian Endometrioid Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  4. Recurrent primary biliary cirrhosis: peritransplant factors and ursodeoxycholic acid treatment post-liver transplant.

    Guy, Jennifer E; Qian, Peiqing; Lowell, Jeffrey A; Peters, Marion G


    Primary biliary cirrhosis (PBC) recurs after orthotopic liver transplantation (OLT) in up to one-third of patients. These patients are typically asymptomatic, can be identified by abnormal liver biochemistries, and have evidence of histologic recurrence on liver biopsy. The effect of treatment on recurrence has not been determined. This pilot study evaluates the factors associated with recurrent PBC and describes our experience using ursodeoxycholic acid treatment in this patient population. Forty-eight patients with PBC were followed for at least 1 yr post-OLT, and 27 patients (56%) developed abnormal serum alkaline phosphatase. Seventeen patients (35%) had evidence of recurrent PBC by liver biopsy. Patients with recurrent PBC had a trend toward longer warm ischemia times and more episodes of acute cellular rejection in the first year posttransplant, but this was not significant in multivariate analysis. Donor or recipient age, donor and recipient cytomegalovirus status, and dose of immunosuppression did not correlate with recurrence of PBC. Those patients diagnosed with recurrent PBC were placed on ursodeoxycholic acid, 15 mg/kg daily, with improvement in serum alkaline phosphatase in the majority. In conclusion, recurrent PBC is not infrequent post-OLT, and ursodeoxycholic acid can be used with some benefit post-OLT. Treatment effects on long-term survival are not known.

  5. Recurrent Primary Spontaneous Pneumothorax is Common Following Chest Tube and Conservative Treatment

    Olesen, Winnie Hedevang; Lindahl-Jacobsen, Rune; Katballe, Niels;


    INTRODUCTION: Previous studies on primary spontaneous pneumothorax reported variable recurrence rates, but they were based on heterogeneous patient populations including secondary pneumothorax. We investigated young patients with primary spontaneous pneumothorax exclusively and used a national...... registry to track readmissions and calculate independent predictors of recurrence. METHODS: A prospective cohort study of consecutive young patients who were admitted over a 5-year period with their first episode of primary spontaneous pneumothorax and treated conservatively with a chest tube. Baseline...... characteristics were obtained from questionnaires presented on admittance. All patients were discharged with fully expanded lungs on chest radiography. Patient charts were identified in the national electronic patient registry for detailed information on readmissions due to recurrent spontaneous pneumothorax...

  6. Re-irradiation of recurrent esophageal cancer after primary definitive radiotherapy

    Kim, Young Suk; Lee, Chang Geol; Kim, Kyung Hwan; Kim, Tae Hyung [Dept. of Radiation Oncology, Yonsei University Health System, Yonsei University College of Medicine, Seoul (Korea, Republic of)


    For recurrent esophageal cancer after primary definitive radiotherapy, no general treatment guidelines are available. We evaluated the toxicities and clinical outcomes of re-irradiation (re-RT) for recurrent esophageal cancer. We analyzed 10 patients with recurrent esophageal cancer treated with re-RT after primary definitive radiotherapy. The median time interval between primary radiotherapy and re-RT was 15.6 months (range, 4.8 to 36.4 months). The total dose of primary radiotherapy was a median of 50.4 Gy (range, 50.4 to 63.0 Gy). The total dose of re-RT was a median of 46.5 Gy (range, 44.0 to 50.4 Gy). The median follow-up period was 4.9 months (range, 2.6 to 11.4 months). The tumor response at 3 months after the end of re-RT was complete response (n = 2), partial response (n = 1), stable disease (n = 2), and progressive disease (n = 5). Grade 5 tracheoesophageal fistula developed in three patients. The time interval between primary radiotherapy and re-RT was less than 12 months in two of these three patients. Late toxicities included grade 1 dysphagia (n = 1). Re-RT of recurrent esophageal cancer after primary radiotherapy can cause severe toxicity.


    Nagane, Motoo; Kobayashi, Keiichi; Saito, Kuniaki; Shiokawa, Yoshiaki


    BACKGROUND. Prognosis of patients with recurrent glioblastoma (GBM) remains dismal, their median overall survival (mOS) ranging from 7 to 10 months. Currently, bevacizumab (BEV), a monoclonal antibody against VEGF, has been widely used since it prolonged progression-free survival (PFS) accompanied with symptom relief in BEV trials. However, improvement of OS seems modest at most, and issues regarding short survival after BEV failure, invasive relapse, and difficulty in determining true progression remain unsolved. Here we examined the patterns of radiological BEV failure in relationship with survival of several post-treatment periods. METHODS. Twenty-five patients with primary GBM who were treated with BEV monotherapy at recurrence in Kyorin University hospital since August 2009 were included in this study. Mean age was 53 yo, 13 males/12 females, median KPS was 60 (30-100), and mOS from the initial surgery was 23.2 months. MRI patterns at BEV progression were determined using modified classification by Nowosielsky et al. (Neurology 2014) as follows: 1) T2-diffuse, 2) cT1-flare up, 3) Primary non-responders, 4) T2-circumscribed, and 5) Remote metastasis. RESULTS. mPFS and mOS of BEV monotherapy were 3.4 and 7.6 months, respectively, and post-BEV mOS was 4.7 months. Frequency and BEV-PFS/post-BEV OS were 1) 20%, 3.8/0.8 months; 2) 40%, 3.4/7.1 months, 3) 24%, 0.9/3.3 months, 4) 8%, 3.7/3.9 months, 5) 8%, 2.0/4.2 months. The cT1-flare up recurrent pattern was found most frequently with relatively better survivals, whereas the T2-diffuse recurrence included fatal brain stem invasion in two cases, resulting in poorer prognosis. CONCLUSIONS. BEV monotherapy showed limited survival benefit and the clinical course after BEV failure may differ by patterns of relapse. Although RANO criteria have been a standard method to determine progression, measurement of T2/FLAIR hyperintensity remains critically controversial. Efforts to improve BEV-based therapy for recurrent GBM

  8. Stage IE Primary Bone Lymphoma:Limb Salvage for Local Recurrence

    Khodamorad Jamshidi


    Full Text Available Background:   Primary bone lymphoma or non-Hodgkin lymphoma of bone is a rare disease. There are only a few case series of stage IE of this condition in medical literature. The aim of this study is to determine the rate of survival   for stage IE after combined modality treatment, the rate of local recurrence, and the results of limb salvage in cases   of local recurrence.     Methods:   We collected data from 61 patients with histologically confirmed PBL treated at the Musculoskeletal   Oncology Department of our hospital from 2000 to 2010. Retrospective evaluation included demographics, symptoms, tumor locations, outcomes of surgical treatment for local recurrence and survival rates. Results:   All patients received Combined Modality Therapy. Overall,five year survival was 89% and five year disease free survival rate was 78%. Local recurrence occurred in 6 patients during follow up period, which was treated surgically     by wide excision and reconstruction. The mean follow-up for the local recurrence group was 36(24-54 months and mortality rate in this group was 17%. Conclusions:   Combined Modality Therapy for stage IE primary bone lymphomaresults in good survival rate. In case   of local recurrence, wide excision and reconstruction improves the outcomes.

  9. Stage IE Primary Bone Lymphoma:Limb Salvage for Local Recurrence

    Khodamorad Jamshidi


    Full Text Available Background:   Primary bone lymphoma or non-Hodgkin lymphoma of bone is a rare disease. There are only a few case series of stage IE of this condition in medical literature. The aim of this study is to determine the rate of survival   for stage IE after combined modality treatment, the rate of local recurrence, and the results of limb salvage in cases   of local recurrence.     Methods:   We collected data from 61 patients with histologically confirmed PBL treated at the Musculoskeletal   Oncology Department of our hospital from 2000 to 2010. Retrospective evaluation included demographics, symptoms, tumor locations, outcomes of surgical treatment for local recurrence and survival rates. Results:   All patients received Combined Modality Therapy. Overall,five year survival was 89% and five year disease free survival rate was 78%. Local recurrence occurred in 6 patients during follow up period, which was treated surgically     by wide excision and reconstruction. The mean follow-up for the local recurrence group was 36(24-54 months and mortality rate in this group was 17%. Conclusions:   Combined Modality Therapy for stage IE primary bone lymphomaresults in good survival rate. In case   of local recurrence, wide excision and reconstruction improves the outcomes.

  10. Results of Limbal Conjunctival Autograft Transplantation in Primary and Recurrent Pterygium Surgery

    Raşit Kılıç


    Full Text Available Objectives: To evaluate the results of limbal conjunctival autograft transplantation in cases with primary and recurrent pterygium. Materials and Methods: A total of 54 eyes of 49 patients who were operated for pterygium with limbal conjunctival autograft technique between April 2011-July 2013 with at least 6 months of follow-up were retrospectively assessed. All cases were distributed into 3 groups according to the postoperative therapy and the primary/recurrent nature of pterygium: Recurrent pterygium with postoperative topical cyclosporin A+hydroxypropylmethylcellulose treatment were included in group 1, primary pterygium with postoperative topical cyclosporin A+hydroxypropylmethylcellulose were included in group 2, and primary pterygium without either topical cyclosporin A or hydroxypropylmethylcellulose were included in group 3. Results: Eleven eyes of 9 patients were detected for group 1, 11 eyes of 11 patients for group 2, and 32 eyes of 29 patients were detected for group 3. Follow-up period was 17±9.1 months for group 1, 14.4±6.1 months for group 2, 13.2±7 months for group 3, and 14.2±7.3 months for all groups. Totally, two recurrences (3.7% were observed as one case for both group 1 (9.1% and group 3 (3.1% during the follow-up period. The recurrence rate between the three groups was not statistically significantly different (p=0.653. Conclusion: Limbal conjunctival autograft technique is an effective and safe technique in excision of primary and recurrent pterygium. (Turk J Ophthalmol 2014; 44: 449-53

  11. Primary Adenoid Cystic Carcinoma of the Skin with Multiple Local Recurrences

    Ivan Dimitrov Tonev


    Full Text Available Primary adenoid cystic carcinoma (PACC of the skin is a rare tumor with fewer than 70 cases studied in detail in the English literature. This type of tumor shows a prolonged course and a growth pattern usually manifested by multiple local recurrences and has a low potential for distant metastases. The most important modality for primary treatment is surgical resection followed by radiotherapy. We report a woman aged 43 years at the time of diagnosis, who presented with a slow-growing nodule in the right axilla without lymph node enlargement. A wide local excision was performed, and the histology revealed an adenoid cystic carcinoma. During the next 24 years, another four local recurrences were excised (the last one in 2015 and confirmed histologically to be adenoid cystic carcinoma. The patient was given 44 Gy of radiotherapy after the second surgery in 1996. PACC of the skin is a rare tumor with insufficient data concerning the efficacy of the surgical technique and chemotherapy and radiotherapy treatment, even more so in the case of multiple recurrences. After the last recurrence, the patient was offered an active follow-up based on the long tumor-free intervals in the past and because the site of the primary tumor allowed further surgical excisions in future recurrences.


    Z S Alekberova


    Full Text Available Summary The patient with primary antiphospholipid syndrome (PAPS, who had two out of three pregnancies with intrauterine premature fetus death, was observed. During the last gestation she had corporeal cesarean section, and alive premature girl was extracted. The diagnosis of PAPS was verified basing on relapsing thromboses, repeated premature fetus death and antiphosphilipid antibodies in absence of some autoimmune disease. The peculiarity of this case was late diagnosis of the syndrome, first two episodes of thromboses were not timely diagnosed (diagnoses were as follows: appendicitis, apoplexy of ovary. Only on the background of the third pregnancy the thrombotic genesis of abdominal syndrome was determined. The specter of intensive therapy was suggested which allowed to prevent the development of "catastrophic ” variant of PAPS developing and to keep the child alive.

  13. Apex-to-Cupola Distance Following VATS Predicts Recurrence in Patients With Primary Spontaneous Pneumothorax.

    Chang, Jia-Ming; Lai, Wu-Wei; Yen, Yi-Ting; Tseng, Yau-Lin; Chen, Ying-Yuan; Wu, Ming-Ho; Chen, Wei; Light, Richard W


    Our study sought to determine whether the size of the residual apical pleural space in young patients with primary spontaneous pneumothorax (PSP) following video-assisted thoracoscopic surgery is associated with the risk of recurrence. We retrospectively reviewed patients (≤30 years' old) with primary spontaneous pneumothorax following thoracoscopic surgery (2002-2010) in a university-affiliated hospital. The size of residual apical pleural space was estimated by measuring the apex-to-cupola distance on a postoperative chest radiograph at 2 time windows: first between postoperative day (POD) 0 and 3, and second between POD 4 and 14. A total of 149 patients were enrolled with a median follow-up of 11.2 months (interquartile range, 0.95-29.5 months), of whom 141 (94.6%) were male with a mean age of 20 years. The postoperative recurrence rate was 11.4%. Comparing the characteristics between the patients with and without recurrent pneumothorax, the patients with recurrence were younger (18.2 + 2.4 vs 20.7 + 3.7 years, P = 0.008), with a lower rate of pleurodesis (35% vs1 69%, P = 0.037), longer apex-to-cupola distance at POD 0 to 3 (22.41 ± 19.56 vs 10.07 ± 10.83 mm, P 10 mm (P = 0.027, OR: 5.319), and no pleurodesis during VATS (P = 0.022, OR: 5.042) were independent risk factors for recurrent pneumothorax. The recurrence rate was not low (11.4%) in young patients with PSP following VATS. Residual apical pleural space with apex-to-cupola distance of 10 mm or greater at POD 0 to 3, younger age, and no pleurodesis would increase postoperative recurrence of primary spontaneous pneumothorax.

  14. Focal salvage therapy for local prostate cancer recurrences after primary radiotherapy : a comprehensive review

    Duijzentkunst, D A Smit; Peters, M; van der Voort van Zyp, J R N; Moerland, M A; van Vulpen, M


    BACKGROUND/AIM: Patients with locally recurrent prostate cancer after primary radiotherapy can be eligible for salvage treatment. Whole-gland salvage techniques carry a high risk of toxicity. A focal salvage approach might reduce the risk of adverse events while maintaining cancer control in careful

  15. Magnetic resonance imaging guided reirradiation of recurrent and second primary head and neck cancer

    Allen M. Chen, MD


    Conclusions: Our preliminary findings show that reirradiation with MRI guided radiation therapy results in effective disease control with relatively low morbidity for patients with recurrent and second primary cancers of the head and neck. The superior soft tissue resolution of the MRI scans that were used for planning and delivery has the potential to improve the therapeutic ratio.

  16. Diabetes due to recurrent pancreatitis secondary to hypercalcemia due to primary hyperparathyroidism

    Sumit Kumar Chakrabarti


    Full Text Available Acute pancreatitis due to hypercalcemia associated with hyperparathyroidism (HPT is not very common. We herein report a case of a 21-year-old woman, who presented with acute pancreatitis. She had a past history of recurrent nephrolithiasis. Subsequent evaluation revealed hypercalcemia (serum calcium: 12.6 mg/dL; low phosphate (2.9 mg/dL with elevated parathyroid hormone (PTH, 156.7 pg/mL and HbA1c (6.9%. Diagnosis of primary HPT (PHPT was made. Recurrent pancreatitis due to hypercalcemia may have resulted in diabetes mellitus.

  17. Successful Treatment of Recurrent Primary Sclerosing Cholangitis after Orthotopic Liver Transplantation with Oral Vancomycin

    Yinka K. Davies


    Full Text Available Primary sclerosing cholangitis (PSC is a progressive, cholestatic disease of the liver that is marked by inflammation of the bile ducts and damage to the hepatic biliary tree. Approximately 60–70% of patients also have inflammatory bowel disease and progression of PSC can lead to ulcerative colitis and cirrhosis of the liver. Due to limited understanding of the etiology and mechanism of PSC, the only existing treatment option is orthotopic liver transplantation (OLT; however, recurrence of PSC, after OLT is estimated to be between 5% and 35%. We discuss the successful treatment of a pediatric patient, with recurrent PSC, after OLT with oral Vancomycin.

  18. Late Recurrent Post-Transplant Primary Biliary Cirrhosis in British Columbia

    Eric M Yoshida


    Full Text Available Late recurrent primary biliary cirrhosis (PBC following orthotopic liver transplant remains a controversial topic. The first documented case of recurrence occurring in 16 patients transplanted for PBC and followed at the authors' institution for longer than one year is presented. A 54-year-old man transplanted for PBC developed a cholestatic pattern of enzyme elevation on post-transplant day (PTD 1305. Repeat antimitochondrial antibody was strongly positive (1:300 to 1:400. A liver biopsy revealed severe bile duct damage, lymphocytic cholangitis, focal periductal noncaseating granuloma and minimal endotheliitis. Recurrent PBC was diagnosed. At the time of orthotopic liver transplant this patient received induction immunosuppression with OKT3 crossed over to cyclosporine (CsA, azathioprine (AZA and prednisone. AZA was discontinued early and maintenance CsA tapered to a target trough level of 150 to 200 ng/mL by PTD 365. Prednisone was withdrawn by PTD 664. CsA levels during PTDs 1225 to 1305 (before elevation of hepatobiliary enzymes were below target at 114 to 166 ng/mL. Of the 16 patients, all but three were maintained on CsA, AZA and prednisone. One was on CsA (trough levels on target and AZA; the other two, including the patient with recurrent PBC, were on CsA only. The trough CsA level of the patient without recurrent PBC has been within the target range. The authors speculate that the underlying defect in immunoregulation in PBC persists post-transplant and that in the patient without recurrent PBC this defect was unmasked by lowered maintenance immunosuppression - allowing recurrence of PBC in a previously stable liver allograft.

  19. Excision and primary closure of pilonidal sinus disease: worthwhile option with an acceptable recurrence rate.

    Gilani, S N S


    BACKGROUND: Treatment of pilonidal sinus disease is controversial. Many claim policy of marsupialisation and healing by secondary intention. This is demanding in terms of nursing care and time lost from work. AIMS: To examine outcome of excision and primary closure of chronic pilonidal disease on recurrence rate and patient\\'s daily activities. PATIENTS AND METHODS: One hundred and fourteen consecutive elective patients who had excision and primary closure of pilonidal sinus disease were reviewed. The demographic data and the post-operative outcome were studied. RESULTS: The recurrence of pilonidal sinus was noted in 9% of patients, wound breakdown occasioning delayed healing in 9%, patients able to drive by day 16 on average. The mean time to return to work was 20.5 days; duration of analgesia, 2.4 days; and duration of antibiotic treatment, 4.7 days. CONCLUSION: Excision and primary closure of chronic pilonidal sinus has low recurrence rate with early return to activities. Primary closure appears to be a cost-effective option for uncomplicated pilonidal sinus disease.

  20. Successful treatment of recurrent renal stones with Cinacalcet in a patient with primary hyperparathyroidism.

    Chauhan, Priyesh; Gittoes, Neil J; Geberhiwot, Tarekegn


    A man aged 72 years with long-standing primary hyperparathyroidism (HPT), a background of recurrent bilateral renal stones and failed parathyroid surgery is described. During the 27 months preceding treatment, episodes of renal colic became increasingly frequent and he required multiple surgical interventions. Given the lack of medical therapies to definitively treat his symptoms, he was started on a trial of the calcimimetic, Cinacalcet. Cinacalcet has previously been shown to reduce hypercalcaemia in patients with primary HPT. Despite this, there is a paucity of evidence to suggest that its use is associated with a long-term reduction in urinary calcium excretion and renal stone recurrence. In our case, within 4 months of starting treatment, serum and urinary calcium had normalised and parathyroid hormone concentrations were within reference ranges. To date, over a 50-month treatment period, there has been a complete cessation in stone formation, and no further urological intervention has been required.

  1. Chronic and Recurrent Depression in Primary Care: Socio-Demographic Features, Morbidity, and Costs

    Elaine M. McMahon


    Full Text Available Background. Major depression is often chronic or recurrent and is usually treated within primary care. Little is known about the associated morbidity and costs. Objectives. To determine socio-demographic characteristics of people with chronic or recurrent depression in primary care and associated morbidity, service use, and costs. Method. 558 participants were recruited from 42 GP practices in the UK. All participants had a history of chronic major depression, recurrent major depression, or dysthymia. Participants completed questionnaires including the BDI-II, Work and Social Adjustment Scale, Euroquol, and Client Service Receipt Inventory documenting use of primary care, mental health, and other services. Results. The sample was characterised by high levels of depression, functional impairment, and high service use and costs. The majority (74% had been treated with an anti-depressant, while few had seen a counsellor (15% or a psychologist (3% in the preceding three months. The group with chronic major depression was most depressed and impaired with highest service use, whilst those with dysthymia were least depressed, impaired, and costly to support but still had high morbidity and associated costs. Conclusion. This is a patient group with very significant morbidity and high costs. Effective interventions to reduce both are required.

  2. In Vitro Chemosensitivity Testing of Primary and Recurrent Breast Carcinomas and Its Clinical Significance

    Zhi LI; Haiping SONG; Wenshan HE; Yuan TIAN; Tao HUANG


    In this study, in vitro chemosensitivity testing was conducted on primary cultured breast cancer cells from 96 patients with breast cancer, and the results showed that the cells from a few patients with primary breast cancer developed multidrug resistance (MDR) prior to the first chemotherapy exposure. All the cells from the recurrent cancer patients had MDR. The findings suggested that patients having MDR would benefit from high-dose chemotherapy (HDC) regimens. In vitro chemosensitivity screening, which was aimed at improving the therapeutic efficacy and minimizing side effects, helps in choosing individualized treatment for breast cancer.

  3. CNS involvement in primary Sjogren Syndrome: assessment of gray and white matter changes with MRI and voxel-based morphometry.

    Tzarouchi, Loukia C; Tsifetaki, Niki; Konitsiotis, Spyridon; Zikou, Anastasia; Astrakas, Loukas; Drosos, Alexandros; Argyropoulou, Maria I


    The purpose of this study was to evaluate with MRI the involvement of gray matter and white matter structures in patients with primary Sjögren syndrome. Fifty-three patients with primary Sjögren syndrome, 18 age- and disease duration-matched patients with systemic sclerosis, and 35 age-matched control subjects were examined for differences in white matter hyperintensities (WMHIs) detected on FLAIR MR images. Differences in brain volume between patients with primary Sjögren syndrome and controls were studied by application of voxel-based morphometry to a 3D T1-weighted sequence. WMHIs were observed in 38 of the 53 patients with primary Sjögren syndrome, six of 18 patients with systemic sclerosis, and 17 of 35 controls. The numbers of WMHIs 2 mm or larger and the number smaller than 2 mm were higher in patients with primary Sjögren syndrome than in controls (≥ 2 mm, p = 0.004; syndrome patients and that in systemic sclerosis patients. After control for age, a positive relation was found between disease duration and total number of WMHIs (p = 0.037) and number of WMHIs 2 mm or larger (p = 0.023) in patients with primary Sjögren syndrome. In comparison with the controls, patients with primary Sjögren syndrome had decreased gray matter volume in the cortex, deep gray matter, and cerebellum. Associated loss of white matter volume was observed in areas corresponding to gray matter atrophy and in the corpus callosum (p syndrome have WMHIs and gray and white matter atrophy, probably related to cerebral vasculitis.

  4. Recurrent blood eosinophilia in ulcerative colitis is associated with severe disease and primary sclerosing cholangitis.

    Barrie, Arthur; Mourabet, Marwa El; Weyant, Katherine; Clarke, Kofi; Gajendran, Mahesh; Rivers, Claudia; Park, Seo Young; Hartman, Douglas; Saul, Melissa; Regueiro, Miguel; Yadav, Dhiraj; Binion, David G


    Eosinophils are implicated in the pathogenesis of inflammatory bowel disease (IBD). A subset of IBD patients develops blood eosinophilia, and the clinical profile of these patients is undefined. We sought to characterize IBD patients with and without eosinophilia. We studied a prospective registry of 1,176 IBD patients followed in a tertiary referral center. Patients who developed eosinophilia at any time were identified by electronic medical record query. We performed a chart review case-control study comparing patients with recurrent eosinophilia versus randomly selected disease-matched patients with no history of eosinophilia. Histological analysis was performed on selected cases and controls. Eosinophilia at any time was more prevalent in ulcerative colitis (UC) patients than Crohn's disease patients (22.2 versus 12.7%), as was recurrent eosinophilia (3.4 versus 0.7%). UC patients with recurrent eosinophilia were predominantly male compared with the control UC population (81.3 versus 46.9%) and had higher rates of colectomy for either medically refractory disease or dysplasia/cancer than control UC patients (56.3 versus 15.6%). Primary sclerosing cholangitis (PSC) occurred in 37.5% of UC patients with recurrent eosinophilia compared with only 3.1% in the UC controls. Histological analysis of random diagnostic samples from UC patients with recurrent eosinophilia demonstrated a normal eosinophil pattern as seen in the control UC population. Eosinophilia-associated UC is a subgroup of IBD associated with severe colitis and PSC. Further studies are warranted to characterize molecular mechanisms underlying eosinophilia-associated UC and to determine optimal approaches for therapy.

  5. Recurrent blood eosinophilia in ulcerative colitis is associated with severe disease and primary sclerosing cholangitis

    Barrie, Arthur; Mourabet, Marwa El; Weyant, Katherine; Clarke, Kofi; Gajendran, Mahesh; Rivers, Claudia; Park, Seo Young; Hartman, Douglas; Saul, Melissa; Regueiro, Miguel; Yadav, Dhiraj; Binion, David G.


    Background and Aims Eosinophils are implicated in the pathogenesis of inflammatory bowel disease (IBD). A subset of IBD patients develops blood eosinophilia and the clinical profile of these patients is undefined. We sought to characterize IBD patients with and without eosinophilia. Methods We studied a prospective registry of 1176 IBD patients followed in a tertiary referral center. Patients who developed eosinophilia at any time were identified by electronic medical record query. We performed a chart review case-control study comparing patients with recurrent eosinophilia versus randomly selected disease matched patients with no history of eosinophilia. Histological analysis was performed on selected cases and controls. Results Eosinophilia at any time was more prevalent in ulcerative colitis (UC) patients than Crohn’s disease patients (22.2% vs. 12.7%), as was recurrent eosinophilia (3.4% vs. 0.7%). UC patients with recurrent eosinophilia were predominantly male compared to the control UC population (81.3% vs. 46.9%) and had higher rates of colectomy for either medically refractory disease or dysplasia/cancer than control UC patients (56.3% vs. 15.6%). Primary sclerosing cholangitis (PSC) occurred in 37.5% of UC patients with recurrent eosinophilia compared to only 3.1% in the UC controls. Histological analysis of random diagnostic samples from UC patients with recurrent eosinophilia demonstrated a normal eosinophil pattern as seen in the control UC population. Conclusions Eosinophilia-associated UC is a subgroup of IBD associated with severe colitis and PSC. Further studies are warranted to characterize molecular mechanisms underlying eosinophilia-associated UC and to determine optimal approaches for therapy. PMID:22855293

  6. Primary anti-phospholipid antibody syndrome causing recurrent venous thrombosis and thrombocytopenia in a patient with Addison's disease.

    Elebrashy, Ibrahim; Yousief, Elham; Saif, Aasem


    We report a case of Addison's disease presenting with recurrent deep venous thrombosis and thrombocytopenia and proved to have primary anti-phospholipid antibody syndrome. The case report highlights the shared autoimmune nature of both diseases.

  7. Re-irradiation for recurrent and second primary cancers of the head and neck.

    Velez, Maria A; Veruttipong, Darlene; Wang, Pin-Chieh; Chin, Robert; Beron, Philip; Abemayor, Elliot; St John, Maie; Chen, Allen M


    To evaluate a single-institutional experience with the use of re-irradiation for recurrent and new primary cancers of the head and neck. The medical charts of 80 consecutive patients who underwent re-irradiation for local-regionally recurrent or second primary head and neck cancer between November 1998 and December 2015 were analyzed. Multivariate analysis was performed using Cox proportional hazard and logistic regression to determine predictors of clinical outcomes. Seventy-six of the 80 patients were evaluable. The median age was 57.5 (range 26.6-84.9); Intensity-modulated radiotherapy (IMRT) was used in 71 (93.4%) patients with a median dose of 60Gy. Thirty-one patients (40.8%) underwent salvage surgery before re-irradiation and 47 (61.8%) received concurrent systemic therapy. The median time interval between radiation courses was 25.3months (range 2-322months). The 2-year estimates of overall survival, progression free survival, locoregional control, and distant control were 51.0%, 31.3%, 36.8% and 68.3%, respectively. Patients who underwent salvage surgery prior to re-irradiation had significantly improved locoregional control, progression free survival, and overall survival (p<0.05, for all). On multivariate analysis, gross tumor volume (GTV) at re-irradiation and interval between radiation courses were associated with improved overall survival. Severe (grade⩾3) late complications were observed in 25 patients (32.8%). Re-irradiation for recurrent or second primary head and neck cancer is feasible and effective in select patients with head and neck cancer. The high observed rate of treatment-related morbidity highlights the continue challenges that accompany this approach. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Photodynamic Therapy Using HPPH in Treating Patients Undergoing Surgery for Primary or Recurrent Head and Neck Cancer


    Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Thyroid Cancer; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Basal Cell Carcinoma of the Lip; Stage I Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage I Follicular Thyroid Cancer; Stage I Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Papillary Thyroid Cancer; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Hypopharynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Adenoid Cystic Carcinoma of the

  9. Characteristics and dynamics of cognitive impairment in patients with primary and recurrent cerebral ischemic hemispheric stroke

    A. A. Kozyolkin


    Full Text Available Acute cerebrovascular disease is a global medical and social problem of the modern angioneurology, occupying leading positions in the structure of morbidity and mortality among adult population of the world. Ischemic stroke – is one of the most common pathology. Today this disease took out the world pandemic. More than 16 million new cases of cerebral infarction recorded in the world each year and it “kills” about 7 million of people. About 111,953 cases of cerebral stroke were registered in 2013 in Ukraine. Cognitive impairment, t hat significantly disrupt daily activities and life of the patient, is one of the most significant post-stroke complications that have social, medical and biological significance. Aim. The purpose of this investigation was to study features and dynamics of cognitive impairments in patients with primary and recurrent cerebral hemispheric ischemic stroke (CHIS in the acute stage of the disease. Materials and methods. To achieve the aim, and the decision of tasks in the clinic of nervous diseases Zaporozhye State Medical University (supervisor - Doctor of Medicine, Professor Kozelkin A. based on the department of acute cerebrovascular disease were performed comparative, prospective cohort study, which included comprehensive clinical and paraclinical examinations of 41 patients (26 men and 15 women aged 45 to 85 years (mean age 66,4 ± 1,4 years with acute left-hemispheric (2 patients and right - hemispheric (39 patients CHIS . First up was a group of 28 patients (19 men and 9 women, mean age 65,6 ± 1,6 years, who suffered from primary CHIS. The second group consisted of 13 patients (7 men and 6 women, mean age 68,1 ± 2,5 years with recurrent CHIS. The groups were matched by age, sex, localization of the lesion and the initial level of neurological deficit. All patients underwent physical examination, neurological examination. Dynamic clinical neurological examination assessing the severity of stroke was conducted

  10. SNPs array karyotyping reveals a novel recurrent 20p13 amplification in primary myelofibrosis.

    Giuseppe Visani

    Full Text Available The molecular pathogenesis of primary mielofibrosis (PMF is still largely unknown. Recently, single-nucleotide polymorphism arrays (SNP-A allowed for genome-wide profiling of copy-number alterations and acquired uniparental disomy (aUPD at high-resolution. In this study we analyzed 20 PMF patients using the Genome-Wide Human SNP Array 6.0 in order to identify novel recurrent genomic abnormalities. We observed a complex karyotype in all cases, detecting all the previously reported lesions (del(5q, del(20q, del(13q, +8, aUPD at 9p24 and abnormalities on chromosome 1. In addition, we identified several novel cryptic lesions. In particular, we found a recurrent alteration involving cytoband 20p13 in 55% of patients. We defined a minimal affected region (MAR, an amplification of 9,911 base-pair (bp overlapping the SIRPB1 gene locus. Noteworthy, by extending the analysis to the adjacent areas, the cytoband was overall affected in 95% of cases. Remarkably, these results were confirmed by real-time PCR and validated in silico in a large independent series of myeloproliferative diseases. Finally, by immunohistochemistry we found that SIRPB1 was over-expressed in the bone marrow of PMF patients carrying 20p13 amplification. In conclusion, we identified a novel highly recurrent genomic lesion in PMF patients, which definitely warrant further functional and clinical characterization.

  11. Sequence alterations of the whole mitochondrial genome in primary and recurrent ovarian carcinomas

    Shi Hong-hui; Song Tian; Pan Ling-ya


    Objective: To investigate mitochondrial DNA (mtDNA) alterations in primary and recurrent ovarian carcinomas to illuminate the impact of chemotherapy on mtDNA.Methods.Complete mtDNA genomes of tumor tissue from 7 pimary ovarian carcinoma patients without treatment and 9 recurrent ones with prior chemotherapies were sequenced as well as their matched normal tissue.MtDNA alterations, including somatic mutations and new polymorphisms and consequent amino-acid alterations were compared between the two groups.Results, A large number of mtDNA new polymorphisms (69) and somatic mutations (17) were found in 16 ovarian carcinoma samples.Chemotherapy might not lead to more, heteroplasmic mutations and consequent aminoacid alterations (P>0.05) in the recurrent ovarian carcinoma patients than in the untreated ones.Conclusions: MtDNA damage was not so certainly made by chemotherapies and some of the mtDNA defects might be part of the disease process rather than a consequence of treatment.

  12. Treatment Challenges of a Primary Vertebral Artery Aneurysm Causing Recurrent Ischemic Strokes

    Davide Strambo


    Full Text Available Background. Extracranial vertebral artery aneurysms are a rare cause of embolic stroke; surgical and endovascular therapy options are debated and long-term complication may occur. Case Report. A 53-year-old man affected by neurofibromatosis type 1 (NF1 came to our attention for recurrent vertebrobasilar embolic strokes, caused by a primary giant, partially thrombosed, fusiform aneurysm of the left extracranial vertebral artery. The aneurysm was treated by endovascular approach through deposition of Guglielmi Detachable Coils in the proximal segment of the left vertebral artery. Six years later the patient presented stroke recurrence. Cerebral angiography and Color Doppler Ultrasound well characterized the unique hemodynamic condition developed over the years responsible for the new embolic event: the aneurysm had been revascularized from its distal portion by reverse blood flow coming from the patent vertebrobasilar axis. A biphasic Doppler signal in the left vertebral artery revealed a peculiar behavior of the blood flow, alternately directed to the aneurysm and backwards to the basilar artery. Surgical ligation of the distal left vertebral artery and excision of the aneurysm were thus performed. Conclusion. This is the first described case of NF1-associated extracranial vertebral artery aneurysm presenting with recurrent embolic stroke. Complete exclusion of the aneurysm from the blood circulation is advisable to achieve full resolution of the embolic source.

  13. Robotic Image-Guided Stereotactic Radiotherapy, for Isolated Recurrent Primary, Lymph Node or Metastatic Prostate Cancer

    Jereczek-Fossa, Barbara Alicja, E-mail: [Department of Radiotherapy, European Institute of Oncology, Milan (Italy); University of Milan, Milan (Italy); Beltramo, Giancarlo [CyberKnife Center CDI, Milan (Italy); Fariselli, Laura [Radiotherapy Unit, Carlo Besta Neurological Institute Foundation, Milan (Italy); Fodor, Cristiana [Department of Radiotherapy, European Institute of Oncology, Milan (Italy); Santoro, Luigi [Department of Epidemiology and Statistics, European Institute of Oncology, Milan (Italy); Vavassori, Andrea; Zerini, Dario [Department of Radiotherapy, European Institute of Oncology, Milan (Italy); Gherardi, Federica [Department of Radiotherapy, European Institute of Oncology, Milan (Italy); University of Milan, Milan (Italy); Ascione, Carmen [Department of Radiotherapy, European Institute of Oncology, Milan (Italy); Seconda Universita degli Studi di Napoli, Naples (Italy); Bossi-Zanetti, Isa; Mauro, Roberta [Department of Radiotherapy, European Institute of Oncology, Milan (Italy); University of Milan, Milan (Italy); Bregantin, Achille; Bianchi, Livia Corinna [CyberKnife Center CDI, Milan (Italy); De Cobelli, Ottavio [Department of Urology, European Institute of Oncology, Milan (Italy); Orecchia, Roberto [Department of Radiotherapy, European Institute of Oncology, Milan (Italy); University of Milan, Milan (Italy)


    Purpose: To evaluate the outcome of robotic CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy (CBK-SRT) for isolated recurrent primary, lymph node, or metastatic prostate cancer. Methods and Materials: Between May 2007 and December 2009, 34 consecutive patients/38 lesions were treated (15 patients reirradiated for local recurrence [P], 4 patients reirradiated for anastomosis recurrence [A], 16 patients treated for single lymph node recurrence [LN], and 3 patients treated for single metastasis [M]). In all but 4 patients, [{sup 11}C]choline positron emission tomography/computed tomography was performed. CBK-SRT consisted of reirradiation and first radiotherapy in 27 and 11 lesions, respectively. The median CBK-SRT dose was 30 Gy in 4.5 fractions (P, 30 Gy in 5 fractions; A, 30 Gy in 5 fractions; LN, 33 Gy in 3 fractions; and M, 36 Gy in 3 fractions). In 18 patients (21 lesions) androgen deprivation was added to CBK-SRT (median duration, 16.6 months). Results: The median follow-up was 16.9 months. Acute toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event). Late toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event and 1 Grade 2 event). Biochemical response was observed in 32 of 38 evaluable lesions. Prostate-specific antigen stabilization was seen for 4 lesions, and in 2 cases prostate-specific antigen progression was reported. The 30-month progression-free survival rate was 42.6%. Disease progression was observed for 14 lesions (5, 2, 5, and 2 in Groups P, A, LN, and M respectively). In only 3 cases, in-field progression was seen. At the time of analysis (May 2010), 19 patients are alive with no evidence of disease and 15 are alive with disease. Conclusions: CyberKnife-based stereotactic radiotherapy is a feasible approach for isolated recurrent primary, lymph node, or metastatic prostate cancer, offering excellent in-field tumor

  14. Rituximab induces resolution of recurrent diffuse alveolar hemorrhage in a patient with primary antiphospholipid antibody syndrome.

    Scheiman Elazary, A; Klahr, P P; Hershko, A Y; Dranitzki, Z; Rubinow, A; Naparstek, Y


    Diffuse alveolar hemorrhage (DAH) is a rare manifestation of primary antiphospholipid antibody syndrome (APS). We describe a patient with primary APS and refractory recurrent episodes of DAH. The patient was admitted 15 times due to recurrent episodes of DAH in a period of 18 months. Multiple immunosuppressive drugs did not improve his condition. Two years after his presentation, he was treated with rituximab (two doses of 1 g, 2 weeks apart). Six months later, the attacks of DAH have gradually disappeared. In a follow-up of more than 2 years after he received rituximab, the patient has had no further admissions due to DAH. Levels of antiphospholipid antibodies were measured during follow-up of 4 years. Anti-β2 glycoprotein IgG titer decreased to normal 6 months after therapy but anticardiolipin (aCL) antibody titer increased. We conclude that rituximab caused a dramatic clinical response in this patient. Anti-β2 glycoprotein IgG correlated better with the clinical response in this patient than aCL.




    Liver transplantation has been accepted as a successful therapeutic tool for irreversible liver diseases such as primary biliary cirrhosis. However, removal of the diseased liver may not eliminate this autoimmune disease, and recurrence of primary biliary cirrhosis in the liver graft has been report




    Liver transplantation has been accepted as a successful therapeutic tool for irreversible liver diseases such as primary biliary cirrhosis. However, removal of the diseased liver may not eliminate this autoimmune disease, and recurrence of primary biliary cirrhosis in the liver graft has been report

  17. Phase II trial of temozolomide plus concurrent whole-brain radiation followed by TNV regimen as adjuvant therapy for patients with newly diagnosed primary CNS lymphoma

    Yong Wang


    Full Text Available Background: Primary central nervous system lymphoma (PCNSL is an aggressive extranodal non-Hodgkin′s lymphoma limited to the CNS. Treatment of PCNSL with high-dose methotrexate (HD-MTX-based chemotherapy and whole-brain radiotherapy (WBRT is associated with high rates of relapse and severe treatment-related neurotoxicity. Aim: To report our experience of treating newly diagnosed PCNSL with temozolomide, nedaplatin, and vincristine (TNV, as the replacement of HD-MTX, in combination with concurrent chemoradiotherapy. Materials and Methods: Newly diagnosed PCNSL patients were given concurrent temozolomide (75 mg/m 2 , orally daily during WBRT. Then, the TNV regimen was given after four weeks. The TNV regimen consisted of temozolomide (200 mg/m 2 orally: Days 1-5, nedaplatin (80 mg/m 2 intravenous: Day 1, and vincristine (1.4 mg/m 2 intravenous: Day 1. Each cycle was of a duration of four weeks and a maximum of six cycles were applied. The primary end point was response to treatment obtained by magnetic resonance imaging (MRI. Secondary end points were progression-free survival (PFS and fewer toxic effects. Results: The study subjects included 14 patients (median age: 53.5, median Karnofsky Performance Scale (KPS: 75. The median number of TNV cycles given was five. Response to treatment: Complete response in 12 (85.7% patients, partial response in 2 (14.3% patients, and none with progressive disease. The objective response rate was 100%, and median PFS was 21.4 months. Toxicity was relatively mild, which mainly included nausea in six and fatigue in five, grade 3-4 hematotoxicity in one, and abnormal liver functions in five patients. No neurotoxicity has been observed till date. Conclusion: The efficacy outcomes in this study are comparable to other reported HD-MTX-based regimens plus WBRT, with an added favorable toxicity profile. Prospective, randomized controlled trials are warranted to confirm such results.

  18. Low recurrence rate of a two-layered closure repair for primary and recurrent midline incisional hernia without mesh

    A.H.M. Dur (Alfons); D. den Hartog (Dennis); W.E. Tuinebreijer (Wim); R.W. Kreis (Robert); J.F. Lange (Johan)


    textabstractBackground: Incisional hernia is a serious complication after abdominal surgery and occurs in 11-23% of laparotomies. Repair can be done, for instance, with a direct suture technique, but recurrence rates are high. Recent literature advises the use of mesh repair. In contrast to this dev

  19. The value of postoperative hepatic regional chemotherapy in prevention of recurrence after radical resection of primary liver cancer

    Zhi Quan Wu; Jia Fan; Shuang Jian Qiu; Jian Zhou; Zhao You Tang


    @@ INTRODUCTION In China, primary liver cancer (PLC) ranks second in cancer mortality since the 1990s. In the field of PLC treatment, surgical resection remains the best,which includes large PLC resection, small PLC resection, re-resection of subclinical recurrence, as well as cytoreduction and sequential resection for unresectable PLC. However, recurrence and metastasis have become the major obstacles for further prolonging survival after resection.

  20. Impact on regional recurrence and survival of axillary surgery in women with node-negative primary breast cancer

    Axelsson, C K; Düring, M; Christiansen, P M;


    BACKGROUND: This study examined whether axillary lymph node dissection (ALND) with removal of many normal lymph nodes resulted in a reduced rate of axillary recurrence and better survival, as reported in recent studies. METHODS: The follow-up analyses were based on 8657 patients with node-negative...... primary breast cancer treated solely by surgery. Median follow-up was 9 years. RESULTS: The number of lymph nodes removed correlated with a reduction in the rate of subsequent axillary recurrence (from 2.1 to 0.4 per cent; P = 0.037), local recurrence (from 7.4 to 3.8 per cent; P

  1. Absceso recidivante por Nocardia asteroides en una paciente portadora de poliglobulia primaria Recurrent brain abscess caused by Nocardia asteroides in a patient with primary polycythaemia

    Carlos Aboal


    aspiration and the beginning of an antimicrobial therapy are essential to the patient’s good evolution. This paper presents a patient with a primary polycythaemia and a recurrent brain abscess by Nocardia asteroides, probably of dental origin.

  2. Recurrence rate following treatment for primary multicystic ameloblastoma: systematic review and meta-analysis.

    Almeida, R de A C; Andrade, E S de S; Barbalho, J C; Vajgel, A; Vasconcelos, B C do E


    Opinions regarding the treatment of multicystic ameloblastoma are divergent due to its benign nature and the high rate of recurrence if not adequately excised. The aim of the present study was to perform a systematic review of the literature for a qualitative and quantitative assessment of studies addressing primary multicystic ameloblastoma with regard to treatment and recurrence. Searches were conducted of the Ovid Medline and Embase databases for articles published up to January 2014. Based on predefined eligibility criteria, studies were selected in a two-stage screening process conducted by two independent reviewers. Quality assessment of the selected articles was performed using the modified criteria of the Agency for Healthcare Research and Quality. The meta-analysis was performed using Review Manager (RevMan) software. Statistical heterogeneity was investigated by performing a χ(2) test at the 5% significance level (Pameloblastoma in comparison to radical treatment (Pameloblastoma with bone resection. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  3. Immunostimulatory sutures that treat local disease recurrence following primary tumor resection

    Intra, Janjira; Zhang Xueqing; Salem, Aliasger K [Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242 (United States); Williams, Robin L; Zhu Xiaoyan [Department of Surgery, Roy J and Lucille Carver College of Medicine, University of Iowa, Iowa City, IA 52242 (United States); Sandler, Anthony D, E-mail: [Department of Surgery and Center for Cancer and Immunology Research, Children' s National Medical Center, Washington DC 20010 (United States)


    Neuroblastoma is a common childhood cancer that often results in progressive minimal residual disease after primary tumor resection. Cytosine-phosphorothioate-guanine oligonucleotides (CpG ODN) have been reported to induce potent anti-tumor immune responses. In this communication, we report on the development of a CpG ODN-loaded suture that can close up the wound following tumor excision and provide sustained localized delivery of CpG ODN to treat local disease recurrence. The suture was prepared by melt extruding a mixture of polylactic acid-co-glycolic acid (PLGA 75:25 0.47 dL g{sup -1}) pellets and CpG ODN 1826. Scanning electron microscopy images showed that the sutures were free of defects and cracks. UV spectrophotometry measurements at 260 nm showed that sutures provide sustained release of CpG ODN over 35 days. Syngeneic female A/J mice were inoculated subcutaneously with 1 x 10{sup 6} Neuro-2a murine neuroblastoma wild-type cells and tumors were grown between 5 to 10 mm before the tumors were excised. Wounds from the tumor resection were closed using CpG ODN-loaded sutures and/or polyglycolic acid Vicryl suture. Suppression of neuroblastoma recurrence and mouse survival were significantly higher in mice where wounds were closed using the CpG ODN-loaded sutures relative to all other groups. (communication)

  4. Are ipsilateral breast tumour invasive recurrences in young (more aggressive than their primary tumours?

    Sigal-Zafrani, B; Bollet, M A; Antoni, G; Savignoni, A; Vincent-Salomon, A; Pierga, J-Y; Salmon, R; Sastre-Garau, X; Fourquet, A


    The characteristics of ipsilateral breast tumour recurrences (IBTRs) relative to those of their primary tumours (PTs) remain scarcely studied. Of 70 young (grades or hormonal receptors were not significantly different in PTs and in IBTRs. The concordance between IBTRs and their PTs was good for histological types. IBTRs with conserved histological types tended to occur more locally, but not significantly sooner than others. These IBTRs had good concordance for hormone receptors. In discordant cases there were as many losses as appearances of the receptors. The concordance was weak for grades, with equivalent numbers of IBTRs graded lower as higher than their PTs. The 10-year overall survival rate was 70%. Neither the conservation of histological type, location, nor of the two combined were associated with deaths. Early (<2 years) IBTRs, tended to be associated with poorer survival (HR=2.24 (0.92-5.41); P=0.08). IBTRs did not display features of higher aggressiveness than PTs. Neither clinical nor histological definition of a true recurrence could be established other than the conservation of the histological type.

  5. Primary squamous cell carcinoma of thyroid gland with local recurrence: ultrasonographic and computed tomographic findings

    Jang, Ja Yoon; Kwon, Kye Won; Kim, Sang Wook [Bundang Jesaeng General Hospital, Seongnam (Korea, Republic of); Youn, In Young [Dept. of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)


    Primary squamous cell carcinoma of the thyroid gland (PSCCT) is a rare malignancy that presents with advanced disease and poor prognosis. It is difficult to diagnose PSCCT in its early stage because of its rarity and lack of typical imaging findings. We experienced an elderly woman with PSCCT confirmed by surgery. Although preoperative fine-needle aspiration revealed no malignancy, surgical resection was performed because the ultrasonogram showed diffuse microcalcifications, which suggested malignancy, and clinically, the mass grew rapidly to compress the trachea. Local tumor recurrence was noted at 3 months after surgery. Surgical resection or repeat biopsy should be considered if a cytologically benign thyroid mass shows imaging or clinical features of malignancy.

  6. Skin test reactivity to female sex hormones in women with primary unexplained recurrent pregnancy loss.

    Ellaithy, Mohamed I; Fathi, Hesham M; Farres, Mohamed N; Taha, Marwa S


    The objective was to examine the hypothesis that primary unexplained recurrent pregnancy loss might be associated with an inappropriate immunologically mediated response to progesterone and/or estrogen. This prospective study included 47 women with two or more documented consecutive early pregnancy losses of unknown etiology, and no previous history of deliveries. Intradermal skin testing was performed in the luteal phase of the cycle (days 16-20) using estradiol benzoate, progesterone, and a placebo of refined sesame oil. Immediate (20 min) and late (24h and 1 week) skin test readings for all cases were compared with those of 12 parous women of comparable age with no history of spontaneous miscarriages, premenstrual disorders, pregnancy, or sex hormone-related allergic or autoimmune diseases. Main outcome measure was skin test reactivity to estradiol and/or progesterone. Immediate skin test reactivity to both hormones was observed among half of the cases at 20 min. A papule after 24h, which persisted for up to 1 week, was observed among 32 (68.1%) and 34 (72.3%) cases at the sites of estrogen and progesterone injection, respectively. 55.3% of cases had combined skin test reactivity to both estradiol and progesterone at 1 week. All women in the control group showed absence of skin test reactivity for both estradiol and progesterone at 20 min, 24h, and 1 week. None of the subjects in either group showed skin test reactivity to placebo. There is an association between primary unexplained recurrent pregnancy loss and skin test reactivity to female sex hormones.

  7. Early detection of recurrences in the follow-up of primary breast cancer in an asymptomatic or symptomatic phase.

    Perrone, Maria Antonietta; Musolino, Antonino; Michiara, Maria; Di Blasio, Beatrice; Bella, Mariangela; Franciosi, Vittorio; Cocconi, Giorgio; Camisa, Roberta; Todeschini, Renata; Cascinu, Stefano


    Periodic follow-up after primary treatment for breast cancer is a common procedure for the early detection of recurrent disease in the asymptomatic state. Anyway, there is no clinical evidence that treatment of metastases may improve the prognosis if applied in the asymptomatic state. The aim of the present study was to investigate the modality of detection of the first relapse in the asymptomatic vs the symptomatic state. We retrospectively analyzed 717 breast cancer patients who had been consecutively referred to the Parma Oncology Division during the period 1986 to December 1988. Recurrences were detected in the course of periodic follow-up. A total of 211 of the 408 patients evaluated had a first relapse with a median follow-up of 94.7 months. Local and distant recurrences were 49% and 47%, respectively. Bone recurrences represented 24% of the total first recurrences, then chest wall recurrences in 23%, local regional nodes in 13%, lung in 7%, liver in 4%, and brain in 2%. The distribution of the studied patients according to recurrence site and asymptomatic or symptomatic state was different: 69% of asymptomatic patients (110) had a local recurrence vs 31% of symptomatic patients (101). A difference in survival was recorded in favor of cases detected in the asymptomatic state (P <0.001). The present study suggests that an early detection of local recurrence might have a favorable impact on the prognosis of patients followed after primary treatment for breast cancer. It should be considered that any difference in survival could also be explained by several "biases" and that breast cancer follow-up is still an area of investigation open to discussion in which many questions remain to be clarified.

  8. Olaparib or Cediranib Maleate and Olaparib Compared With Standard Platinum-Based Chemotherapy in Treating Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer


    Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Endometrial Undifferentiated Carcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Tumor; Ovarian Seromucinous Carcinoma; Ovarian Serous Tumor; Ovarian Transitional Cell Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  9. Why is "blindsight" blind? A new perspective on primary visual cortex, recurrent activity and visual awareness.

    Silvanto, Juha


    The neuropsychological phenomenon of blindsight has been taken to suggest that the primary visual cortex (V1) plays a unique role in visual awareness, and that extrastriate activation needs to be fed back to V1 in order for the content of that activation to be consciously perceived. The aim of this review is to evaluate this theoretical framework and to revisit its key tenets. Firstly, is blindsight truly a dissociation of awareness and visual detection? Secondly, is there sufficient evidence to rule out the possibility that the loss of awareness resulting from a V1 lesion simply reflects reduced extrastriate responsiveness, rather than a unique role of V1 in conscious experience? Evaluation of these arguments and the empirical evidence leads to the conclusion that the loss of phenomenal awareness in blindsight may not be due to feedback activity in V1 being the hallmark awareness. On the basis of existing literature, an alternative explanation of blindsight is proposed. In this view, visual awareness is a "global" cognitive function as its hallmark is the availability of information to a large number of perceptual and cognitive systems; this requires inter-areal long-range synchronous oscillatory activity. For these oscillations to arise, a specific temporal profile of neuronal activity is required, which is established through recurrent feedback activity involving V1 and the extrastriate cortex. When V1 is lesioned, the loss of recurrent activity prevents inter-areal networks on the basis of oscillatory activity. However, as limited amount of input can reach extrastriate cortex and some extrastriate neuronal selectivity is preserved, computations involving comparison of neural firing rates within a cortical area remain possible. This enables "local" read-out from specific brain regions, allowing for the detection and discrimination of basic visual attributes. Thus blindsight is blind due to lack of "global" long-range synchrony, and it functions via "local

  10. Non-psychogenic polydipsia in 45-year-old man with primary hyperparathyroidism and recurrent bilateral nephrolithiasis

    Rahmat Cahyanur


    Full Text Available Non-psychogenic polydipsia with hyponatremia is a rare clinical presentation. Primary hyperparathyroidism is a disorder of calcium, phosphate, and bone metabolism caused by increased level of parathyroid hormone (PTH. It is estimated the incidence of primary hyperparathyroidism are 21.6 per 100,000 person a year. This case report describe a 45-year-old man presented with non-psychogenic polydipsia. This patient drank a lot of water out of the fear of recurrent kidney stones. He had history of recurrent nephrolithiasis with hypercalcemia. We investigate further the cause of hypercalcemia and we diagnosed primary hyperparathryoidism as the cause. (Med J Indones. 2012;21:230-4Keywords: Hyponatremia, non-psychogenic polydipsia, primary hyperparathyroidism

  11. Expression and lymphatic microvessel density in primary tumors of node-neagtive colorectal cancer patients predict disease recurrence

    Doekhie, F.S.; Morreau, H.; de Bock, G.H.; Speetjens, F.M.; Dekker-Ensink, N.G.; Putter, H.; vand e Velde, C.J.H.; Tollenaar, R.A.E.M.; Kuppen, P.J.K.; Sialyl lewis, X.


    Up to 30% of curatively resected colorectal cancer patients with tumor-negative lymph nodes, show disease recurrence. We assessed whether these high-risk patients can be identified by examining primary tumors for the following blood and lymphatic vasculature markers: A) sialyl Lewis X (sLeX),

  12. Incisional hernia recurrence following 'vest-over-pants' or vertical mayo repair of primary hernias of the midline

    R.W. Luijendijk; M.H.M. Lemmen (M. H M); W.C.J. Hop (Wim); J.C.J. Wereldsma


    textabstractA series of 68 primary midline incisional hernias with a vertical Mayo repair was evaluated retrospectively. Patients without documented hernia recurrence following this repair were invited for physical examination. Life- table methods were used for statistical analysis. The 1-, 3-, 5-,

  13. Effects on functional outcome after IORT-containing multimodality treatment for locally advanced primary and locally recurrent rectal cancer

    Mannaerts, GHH; Rutten, HJT; Martijn, H; Hanssens, PEJ; Wiggers, T


    Purpose: In the treatment of patients with locally advanced primary or locally recurrent rectal cancer, much attention is focused on. the oncologic outcome. Little is known about the functional outcome. In this study, the functional outcome after a multimodality treatment for locally advanced primar

  14. A gene expression signature that can predict the recurrence of tamoxifen-treated primary breast cancer.

    Chanrion, Maïa; Negre, Vincent; Fontaine, Hélène; Salvetat, Nicolas; Bibeau, Frédéric; Mac Grogan, Gaëtan; Mauriac, Louis; Katsaros, Dionyssios; Molina, Franck; Theillet, Charles; Darbon, Jean-Marie


    The identification of a molecular signature predicting the relapse of tamoxifen-treated primary breast cancers should help the therapeutic management of estrogen receptor-positive cancers. A series of 132 primary tumors from patients who received adjuvant tamoxifen were analyzed for expression profiles at the whole-genome level by 70-mer oligonucleotide microarrays. A supervised analysis was done to identify an expression signature. We defined a 36-gene signature that correctly classified 78% of patients with relapse and 80% of relapse-free patients (79% accuracy). Using 23 independent tumors, we confirmed the accuracy of the signature (78%) whose relevance was further shown by using published microarray data from 60 tamoxifen-treated patients (63% accuracy). Univariate analysis using the validation set of 83 tumors showed that the 36-gene classifier is more efficient in predicting disease-free survival than the traditional histopathologic prognostic factors and is as effective as the Nottingham Prognostic Index or the "Adjuvant!" software. Multivariate analysis showed that the molecular signature is the only independent prognostic factor. A comparison with several already published signatures demonstrated that the 36-gene signature is among the best to classify tumors from both training and validation sets. Kaplan-Meier analyses emphasized its prognostic power both on the whole cohort of patients and on a subgroup with an intermediate risk of recurrence as defined by the St. Gallen criteria. This study identifies a molecular signature specifying a subgroup of patients who do not gain benefits from tamoxifen treatment. These patients may therefore be eligible for alternative endocrine therapies and/or chemotherapy.

  15. Imaging of chronic recurrent multifocal osteomyelitis of childhood first presenting with isolated primary spinal involvement

    Anderson, S.E. [Department of Radiology, University Hospital of Bern, Inselspital, 3010, Bern (Switzerland); Heini, P.; Kalbermatten, D. [Department of Orthopedic Surgery, University Hospital of Bern, Inselspital, Bern (Switzerland); Sauvain, M.J. [Department of Pediatric Rheumatology, University Hospital of Bern, Inselspital, Bern (Switzerland); Stauffer, E. [Department of Pathology, University Hospital of Bern, Inselspital, Bern (Switzerland); Geiger, L. [Section Nuclear Medicine, Department of Radiology, University Hospital of Bern, Inselspital, Bern (Switzerland); Johnston, J.O. [Department of Orthopedic Surgery, University of California at San Francisco, San Francisco, California (United States); Roggo, A. [Department of Surgery, University Hospital of Bern, Inselspital, Bern (Switzerland); Steinbach, L.S. [Department of Radiology, University of California at San Francisco, San Francisco, California (United States)


    Initial presentation with primary spinal involvement in chronic recurrent multifocal osteomyelitis of childhood (CRMO) is rare. Our objective was to review the imaging appearances of three patients who had CRMO who initially presented with isolated primary spinal involvement.Design and patients The imaging, clinical, laboratory and histology findings of the three patients were retrospectively reviewed. Imaging included seven spinal MR imaging scans, one computed tomography scan, nine bone scans, two tomograms and 16 radiographs. These were reviewed by two musculoskeletal radiologists and a consensus view is reported. All three patients presented with atraumatic spinal pain and had extensive bone spinal pathology. The patients were aged 11, 13 and 12 years. There were two females and one male.Results and conclusions The initial patient had thoracic T6 and T8 vertebra plana. Bone scan showed additional vertebral body involvement. Follow-up was available over a 3 year period. The second patient had partial collapse of T9 and, 2 years later, of C6. Subsequently extensive multifocal disease ensued and follow-up was available over 8 years. The third patient initially had L3 inferior partial collapse and 1 year later T8 involvement with multifocal disease. Follow-up was available over 3 years. The imaging findings of the three patients include partial and complete vertebra plana with a subchondral line adjacent to endplates associated with bone marrow MR signal alterations. Awareness of the imaging appearances may help the radiologist to include this entity in the differential diagnosis in children who present with spinal pathology and no history of trauma. Histopathological examination excludes tumor and infection but with typical imaging findings may not always be necessary. (orig.)

  16. Recurrent Primary Synovial Sarcoma of Median Nerve: A Case Report and Literature Review.

    Bhat, A K; Jayakrishnan, K N; Acharya, A M


    We report a case of intraneural synovial sarcoma of the median nerve in a 39 year old lady with multiple local recurrences over thirteen years with no distant metastasis. The diagnosis of biphasic type of synovial sarcoma was confirmed by histopathology and immunohistochemistry. At the time of the fourth recurrence below elbow amputation was performed. This case is being reported for its rarity and propensity for local recurrence without distant metastasis.

  17. High-grade primary myxoid lung sarcoma presenting as recurrent hemorrhagic pleural effusions in a young woman.

    Tahir, Hassan; Coleman, Cinthia; Sagi, Jahnavi; Wani, Adil; Daruwalla, Vistasp


    Primary lung sarcomas are rare but aggressive tumors accounting for less than 0.5% of all lung tumors. The diagnosis of primary lung sarcoma should only be considered after exclusion of other sites. A 32-year-old female presented with recurrent hemorrhagic pleural effusions, shortness of breath and persistent cough. Pleural effusion was drained twice, and each time its analysis was normal. Patient developed atelectasis of left lung with hemothorax for which she underwent video-assisted thoracoscopic surgery. A large mass was found compressing the entire lower lobe of left lung with extension into mediastinum, the biopsy of which showed myxoid sarcoma. The tumor was inoperable and options of chemotherapy or radiotherapy were discussed with the patient. Primary lung sarcoma can rarely present with recurrent hemorrhagic pleural effusion. A high degree of suspicion is required for early diagnosis as large hemothorax on computed tomography or chest X-ray may obscure lung mass and make its diagnosis difficult.

  18. Radiation therapy of CNS lymphoma

    Imai, Yutaka; Wako, Tadashi (Shinshu Univ., Matsumoto, Nagano (Japan). Faculty of Medicine)


    Six cases of the CNS malignant lymphoma occurring among 165 cases seen between 1975 -- 1981 were reviewed. Two cases had primary brain mass lesions and one case had a secondary brain mass in the systemic remission period. Two cases had primary extradural spinal mass lesions and one case had a secondary extradural spinal mass in the systemic relapse period. All patients were treated with radiotherapy. Irradiation fields, doses and those effects were discussed. Whole brain irradiation more than 40 Gy was recommended for brain lesion. Prognosis of the secondary case without systemic remission was poor.

  19. Bevacizumab in Reducing CNS Side Effects in Patients Who Have Undergone Radiation Therapy to the Brain for Primary Brain Tumor, Meningioma, or Head and Neck Cancer


    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Malignant Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineocytoma; Malignant Neoplasm; Meningeal Melanocytoma; Radiation Toxicity; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Brain Tumor; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Basal Cell Carcinoma of the Lip; Stage I Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage I Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma

  20. Evaluation of 1p Losses in Primary Carcinomas, Local Recurrences and Peripheral Metastases from Colorectal Cancer Patients

    Lin Thorstensen


    Full Text Available Cytogenetic and molecular genetic analyses of colorectal adenomas and carcinomas have shown that loss of the distal part of chromosome arm 1p is common, particularly in tumors of the left colon. Because the importance of 1p loss in colorectal cancer metastases is unknown, we compared the frequency, exact site and extent of ip deletions in primary carcinomas (n=28, local recurrences (n=19 and metastases (n=33 from 67 colorectal cancer patients using 14 markers in an allelic imbalance study. Loss of 1p was found in 50% of the primary carcinomas, 33% of the local recurrences, and 64% of the metastases, revealing a significant difference between the local recurrences and the metastases (P=.04. The smallest region of 1p deletion overlap (SRO defined separately for each group of lesions had the region between markers Di S2647 and D1 S2644, at 1 p35-36, in common. The genes PLA2G2A (1p35.1-36 and TP73 (1p36.3 were shown to lie outside this consistently lost region, suggesting that neither of them are targets for the 1p loss. In the second part of the study, microdissected primary carcinomas and distant metastases from the same colorectal cancer patients (n=18 were analyzed, and the same 1p genotype was found in the majority of patients (12/18, 67%. The finding that primary carcinoma cells with metastatic ability usually contain 1p deletions, and that some cases lacking 1p alterations in the primary tumor acquire such changes during growth of a metastatic lesion, supports the notion that 1p loss may be important both early and late in colorectal carcinogenesis, with the apparent exception of local recurrences.

  1. Standard fractionation intensity modulated radiation therapy (IMRT of primary and recurrent glioblastoma multiforme

    Fuller Clifton D


    Full Text Available Abstract Background Intensity-modulated radiation therapy (IMRT affords unparalleled capacity to deliver conformal radiation doses to tumors in the central nervous system. However, to date, there are few reported outcomes from using IMRT, either alone or as a boost technique, for standard fractionation radiotherapy for glioblastoma multiforme (GBM. Methods Forty-two patients were treated with IMRT alone (72% or as a boost (28% after 3-dimensional conformal radiation therapy (3D-CRT. Thirty-three patients with primary disease and 9 patients with recurrent tumors were included. Thirty-four patients (81% had surgery, with gross tumor resection in 13 patients (36%; 22 patients (53% received chemo-radiotherapy. The median total radiation dose for all patients was 60 Gy with a range from 30.6 to 74 Gy. Standard fractions of 1.8 Gy/day to 2.0 Gy/day were utilized. Results Median survival was 8.7 months, with 37 patients (88% deceased at last contact. Nonparametric analysis showed no survival difference in IMRT-boost vs. IMRT-only groups. Conclusion While technically feasible, preliminary results suggest delivering standard radiation doses by IMRT did not improve survival outcomes in this series compared to historical controls. In light of this lack of a survival benefit and the costs associated with use of IMRT, future prospective trials are needed to evaluate non-survival endpoints such as quality of life and functional preservation. Short of such evidence, the use of IMRT for treatment of GBM needs to be carefully rationalized.

  2. Biliary strictures and recurrence after liver transplantation for primary sclerosing cholangitis: A retrospective multicenter analysis.

    Hildebrand, Tatiana; Pannicke, Nadine; Dechene, Alexander; Gotthardt, Daniel N; Kirchner, Gabriele; Reiter, Florian P; Sterneck, Martina; Herzer, Kerstin; Lenzen, Henrike; Rupp, Christian; Barg-Hock, Hannelore; de Leuw, Philipp; Teufel, Andreas; Zimmer, Vincent; Lammert, Frank; Sarrazin, Christoph; Spengler, Ulrich; Rust, Christian; Manns, Michael P; Strassburg, Christian P; Schramm, Christoph; Weismüller, Tobias J


    Liver transplantation (LT) is the only definitive treatment for patients with end-stage liver disease due to primary sclerosing cholangitis (PSC), but a high rate of biliary strictures (BSs) and of recurrent primary sclerosing cholangitis (recPSC) has been reported. In this multicenter study, we analyzed a large patient cohort with a long follow-up in order to evaluate the incidence of BS and recPSC, to assess the impact on survival after LT, and to identify risk factors. We collected clinical, surgical, and laboratory data and records on inflammatory bowel disease (IBD), immunosuppression, recipient and graft outcome, and biliary complications (based on cholangiography and histology) of all patients who underwent LT for PSC in 10 German transplant centers between January 1990 and December 2006; 335 patients (68.4% men; mean age, 38.9 years; 73.5% with IBD) underwent transplantation 8.8 years after PSC diagnosis with follow-up for 98.8 months. The 1-, 5-, and 10-year recipient and graft survival was 90.7%, 84.8%, 79.4% and 79.1%, 69.0%, 62.4%, respectively. BS was diagnosed in 36.1% after a mean time of 3.9 years, and recPSC was diagnosed in 20.3% after 4.6 years. Both entities had a significant impact on longterm graft and recipient survival. Independent risk factors for BS were donor age, ulcerative colitis, chronic ductopenic rejection, bilirubin, and international normalized ratio (INR) at LT. Independent risk factors for recPSC were donor age, IBD, and INR at LT. These variables were able to categorize patients into risk groups for BS and recPSC. In conclusion, BS and recPSC affect longterm graft and patient survival after LT for PSC. Donor age, IBD, and INR at LT are independent risk factors for BS and recPSC and allow for risk estimation depending on the recipient-donor constellation.

  3. Surgical techniques and adjuvants for the management of primary and recurrent pterygia.

    Hovanesian, John A; Starr, Christopher E; Vroman, David T; Mah, Francis S; Gomes, Jose A P; Farid, Marjan; Shamie, Neda; Davidson, Richard S; John, Thomas; Holland, Edward J; Kim, Terry


    The removal and rate of recurrence of pterygium have been discussed for years. The disorder is highly associated with environmental factors, and recurrence rates can be unacceptably high and cannot be successfully predicted. New techniques and graft preparations and postoperative management strategies are helping to reduce the recurrence rates and provide an ocular surface that is near ideal for future cataract or refractive surgery. This review discusses the advantages and disadvantages of various treatment strategies. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  4. Primary malignant melanoma of the vagina with repeated local recurrences and brain metastasis

    Li-Te Lin


    Full Text Available Malignant melanoma of the vagina, a very rare malignancy, has a notoriously aggressive behavior associated with a high risk of local recurrence and distant metastasis. At present, there are various treatment options for this disease but no standard guideline. We describe a case of a 54-year-old woman with a locally advanced melanoma of the vagina, who underwent radical surgery, biochemotherapy with interferon-α-2b, chemotherapy, radiotherapy, and repeat excision of local recurrent lesions and brain metastasis. In conclusion, malignant melanoma of the vagina has a high risk for local recurrence. Repeated local excision followed by biochemotherapy is a tolerable treatment.

  5. CNS development: an overview

    Nowakowski, R. S.; Hayes, N. L.


    The basic principles of the development of the central nervous system (CNS) are reviewed, and their implications for both normal and abnormal development of the brain are discussed. The goals of this review are (a) to provide a set of concepts to aid in understanding the variety of complex processes that occur during CNS development, (b) to illustrate how these concepts contribute to our knowledge of the normal anatomy of the adult brain, and (c) to provide a basis for understanding how modifications of normal developmental processes by traumatic injury, by environmental or experiential influences, or by genetic variations may lead to modifications in the resultant structure and function of the adult CNS.

  6. Health-Related Quality of Life after surgery for primary advanced rectal cancer and recurrent rectal cancer

    Thaysen, Henriette Vind; Jess, Per; Laurberg, Søren


    Aim: A review of the literature was undertaken to provide an overview of Health-related quality of life (HRQoL) after surgery for primary advanced or recurrent rectal cancer and to outline proposals for future HRQoL studies in this area. Method: A systematic literature search was undertaken. Only...... studies concerning surgery for primary advanced or recurrent rectal cancer and describing methods used for measuring HRQoL were considered. Results Seven studies were identified including two prospective longitudinal, three cross-sectional and two based on qualitative data. Global quality of life...... cancer. Larger prospective longitudinal studies are needed to improve information on the effects of this extensive surgery on quality of life....

  7. CNS infections in Greenland

    Nordholm, Anne Christine; Søborg, Bolette; Andersson, Mikael


    BACKGROUND: Indigenous Arctic people suffer from high rates of infectious diseases. However, the burden of central nervous system (CNS) infections is poorly documented. This study aimed to estimate incidence rates and mortality of CNS infections among Inuits and non-Inuits in Greenland...... and in Denmark. METHODS: We conducted a nationwide cohort study using the populations of Greenland and Denmark 1990-2012. Information on CNS infection hospitalizations and pathogens was retrieved from national registries and laboratories. Incidence rates were estimated as cases per 100,000 person......-years. Incidence rate ratios were calculated using log-linear Poisson-regression. Mortality was estimated using Kaplan-Meier curves and Log Rank test. RESULTS: The incidence rate of CNS infections was twice as high in Greenland (35.6 per 100,000 person years) as in Denmark (17.7 per 100,000 person years...

  8. Histopathological, immunohistochemical, and image analytic parameters characterizing the stromal component in primary and recurrent giant cell tumor of bone.

    Saxena, Charu Chandra; Safaya, Rajni; Kawatra Madan, Neha; Khan, Shah Alam; Iyer, Venkateswaran K


    Giant cell tumor (GCT) of bone is a benign locally aggressive tumor whose biological behavior is unpredictable. Currently, there are no definitive clinical, histological, biochemical, or immunological parameters that can predict its behavior. This study was undertaken to examine whether delineation of reactive and neoplastic stromal component of GCT can help in this regard. 55 cases of GCT (30 primary, 25 recurrent) were subjected to histopathological grading, immunohistochemistry, and image analysis. Spindling of stroma was more frequent in recurrent GCT with 64% cases having more than 50% spindled stroma (p group (24.75% and 7.7%, respectively). A single numerical parameter encompassing stromal cell population and its proliferation was derived as ratio of PCNA/CD68 and PCNA/α1-ACT. Both ratios were higher in recurrent (0.81 ± 0.38; 1.58 ± 1.50) than in primary GCT (0.58 ± 0.62; 0.34 ± 0.29) (p = 0.002; 0.01). On image analysis, parameters significantly different between the two groups were nuclear area and nuclear integrated optical density. It was thus concluded that recurrent GCT shows higher grade, increased mitosis, more spindling, fewer reactive components, and higher proliferation than primary GCT. Delineation of reactive component (α1-ACT positive) and proliferating component (PCNA positive cells) using immunohistochemistry with calculation of the PCNA/ACT ratio delivers more information than image analysis.

  9. Classification of ipsilateral breast tumor recurrence after breast-conserving therapy: new primary cancer allows a good prognosis.

    Nishimura, Seiichiro; Takahashi, Kaoru; Akiyama, Futoshi; Oguchi, Masahiko; Tada, Keiichiro; Makita, Masujiro; Iwase, Takuji; Yoshimoto, Masataka; Yamashita, Takashi; Sakamoto, Goi; Kasumi, Fujio


    To classify and assess ipsilateral breast tumor recurrences (IBTR) after breast-conserving therapy. Between 1986 and 2001, 2,137 patients who had breast cancer underwent breast-conserving surgery with or without radiotherapy at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. Of these patients, 83 (3.9%) had an IBTR. We classified the IBTR as a new primary cancer (NP) if the primary tumor had completely negative margins at first operation by detailed pathological examination and if the IBTR had an intraductal component. All other IBTRs were judged true local recurrence (TR). Of the 83 patients, 42 patients were classified as TR (29 had no radiotherapy) and 41 as NP (40 had no radiotherapy). Mean time to disease recurrence was 37 months for TR (52% were within 2 years) versus 55 months for NP (19% were within 2 years) (p=0.031). Six patients (14%) with TR did not receive re-operation, and 67% received salvage mastectomy and 19% re-lumpectomy. All cases of NP were operable, 78% underwent salvage mastectomy and 22% underwent re-lumpectomy. Distant metastases were observed in 33% of patients with TR and 5% of patients with NP, and cause-specific death occurred in 6 cases with TR and in one with NP. The patients with NP had improved 5-year rates of overall survival (NP 91% vs. TR 76%, P=0.0627) and distant disease-free survival (NP 93% vs. TR 61%, P=0.0028). Patients with NP more often developed contralateral breast cancer (NP 37% vs. TR 12%, P=0.018) Patients with NP had better survival rates than those with TR. Distinguishing new primary breast carcinomas from local disease recurrences may have importance in therapeutic decisions and chemoprevention strategies.

  10. Switching from tacrolimus to cyclosporine A to prevent primary biliary cirrhosis recurrence after living-donor liver transplantation.

    Shiba, Hiroaki; Wakiyama, Shigeki; Futagawa, Yasuro; Gocho, Takeshi; Ito, Ryusuke; Furukawa, Kenei; Ishida, Yuichi; Misawa, Takeyuki; Yanaga, Katsuhiko


    Recurrence of primary biliary cirrhosis (PBC) after liver transplantation has been shown to negatively affect graft and patient survival. Recently, protective effects of cyclosporine A against PBC recurrence after liver transplantation have been reported. Participants were 4 patients who underwent living-donor liver transplantation (LDLT) for end-stage liver disease due to PBC. Tacrolimus was used for initial immunosuppression, and this was switched to cyclosporine A at least 3 months after liver transplantation. Targeted trough level of cyclosporine A was 20 times that of tacrolimus. We assessed liver and renal function, as well as antimitochondrial M2 antibody for recipients prior to LDLT, as well as before and after switching immunosuppressive agents. Patients were 1 man and 3 women, and they were ages 45 to 47 years at LDLT. Timing of switching from tacrolimus to cyclosporine A was 13, 3, 7, and 4 months respectively after liver transplantation, and all 4 patients have been on cyclosporine A without adverse effects at 20 to 46 months after transplantation. In 2 of 4 patients who had high titers of antimitochondrial M2 antibody before transplantation, antibody titer did not elevate after LDLT. In the other 2 patients without elevation of antimitochondrial M2 antibody, the titer did not turn positive. Switching from tacrolimus to cyclosporine A was possible without medical problems, and all patients exhibit no recurrence of PBC. Cyclosporine A may be useful for prevention of PBC recurrence after LDLT.

  11. {sup 18F} FDG PET Demonstration of Cancer Recurrence Presenting as Dermatomyositis in a Rare Case of Primary Pleural Lymphoma

    Lee, Sang Mi; Kim, Yu Kyeong; Lee, Jong Jin; Lee, Yoon Jong; Kim, Hye Ryung; Choe, Gheeyoung [Seoul National Univ. College of Medicine/Bundang Hospital, Seoul (Korea, Republic of); Lee, Jeong Won [Jeju National Univ. Hospital, Jeju (Korea, Republic of)


    Dermatomyositis (DM) or polymyositis (PM) are possibly considered to have an association with malignancies. We describe a case of dermatomyositis in which {sup 18F} fluorodeoxyglucose (FDG)positron emission tomography (PET) was able to detect cancer recurrence earlier than any other modality in a patient with a history of primary pleural lymphoma, a very rare condition of malignancy. Further, a typical finding of dermatomyositis is diffuse hypermetabolism in the bilateral proximal shoulder and pelvic girdle areas was shown on {sup 18F} FDG PET, which can implicate the inflammatory process in the skeletal muscle in dermatomyosistis. This case well illustrates the characteristic {sup 18F} FDG findings of dermatomyositis as well as a capability of {sup 18F} FDG PET in detection of recurrence of lymphoma, even in a rare condition.

  12. CNS Involvement in the Non-Hodgkin's Lymhoma

    Suh, Chang Ok; Kim, Gwi Eon; Park, Chang Yun; Kim, Byung Soo [Yonsei University College of Medicine, Seoul (Korea, Republic of)


    Two cases of primary malignant lymphoma of the brain and six cases of secondary CNS lymphoma seen at Yonsei cancer center, radiotherapy department for recent 4 years are presented. Primary lymphomas revealed single tumor mass on corpus callosum area and secondary lymphoma were intracranial (3 cases) or leptomeningeal type (3 cases). Histology of primary lymphoma were reticulum cell sarcoma and secondary lymphomas were either diffuse histiocytic or diffuse poorly differentiated lymphocytic lymphoma. All patients showed good response to radiation. Two patients with primary CNS lymphoma and two of six secondary CNS lymphoma are alive after radiotherapy (34, 31, 26, 12 months). But the prognosis of secondary CNS lymphoma is grave, because of progressive systemic disease. Incidence, risk factors, diagnosis and therapeutic management of CNS involvement are also discussed.

  13. [Importance of the primary physician for pain management in patients with recurrent advanced cancer--a questionnaire survey].

    Konishi, Toshiro; Sasaki, Tsuneo; Aiba, Keisuke; Fukutomi, Takashi; Kakegawa, Kimiko; Okubo, Takashi


    With the objective of clarifying points that needed improvement to provide earlier and better treatment of pain by assessing the current state of cancer pain management in Japan, we conducted a questionnaire survey about pain management in patients with advanced/recurrent cancer who were suffering from pain. The results of the survey revealed that it is important for primary physician to place greater emphasis on pain management when treating cancer patients, to inform patients that the doctor should always be told if the patient has pain, and provide appropriate information about medical narcotics to their patients. The team approach to management of cancer has been increasing in importance recently. This survey suggested it is important for primary physicians, who play a central role in such teams, to listen to their patients' complaints about symptoms including pain. Furthermore, it should be remembered that patients are eager to establish a good, trusting relationship with their primary physician.

  14. High-grade primary myxoid lung sarcoma presenting as recurrent hemorrhagic pleural effusions in a young woman

    Hassan Tahir


    Full Text Available Primary lung sarcomas are rare but aggressive tumors accounting for less than 0.5% of all lung tumors. The diagnosis of primary lung sarcoma should only be considered after exclusion of other sites. A 32-year-old female presented with recurrent hemorrhagic pleural effusions, shortness of breath and persistent cough. Pleural effusion was drained twice, and each time its analysis was normal. Patient developed atelectasis of left lung with hemothorax for which she underwent video-assisted thoracoscopic surgery. A large mass was found compressing the entire lower lobe of left lung with extension into mediastinum, the biopsy of which showed myxoid sarcoma. The tumor was inoperable and options of chemotherapy or radiotherapy were discussed with the patient. Primary lung sarcoma can rarely present with recurrent hemorrhagic pleural effusion. A high degree of suspicion is required for early diagnosis as large hemothorax on computed tomography or chest X-ray may obscure lung mass and make its diagnosis difficult.

  15. Evaluation of several FDG PET parameters for prediction of soft tissue tumour grade at primary diagnosis and recurrence

    Fendler, Wolfgang P. [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Department of Nuclear Medicine, Munich (Germany); Chalkidis, Rebecca P.; Ilhan, Harun [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Knoesel, Thomas [Ludwig-Maximilians-University of Munich, Institute of Pathology, Munich (Germany); Herrmann, Ken [Julius-Maximilians-University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Issels, Rolf D.; Lindner, Lars H. [Ludwig-Maximilians-University of Munich, Department of Internal Medicine III, Munich (Germany); Ludwig-Maximilians-University of Munich, Comprehensive Cancer Center, Munich (Germany); Bartenstein, Peter [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Ludwig-Maximilians-University of Munich, Comprehensive Cancer Center, Munich (Germany); Cyran, Clemens C. [Ludwig-Maximilians-University of Munich, Department of Clinical Radiology, Munich (Germany); Hacker, Marcus [Vienna General Hospital, Department of Nuclear Medicine, Vienna (Austria)


    This study evaluates the diagnostic accuracy of SUV-based parameters derived from [{sup 18} F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in order to optimize non-invasive prediction of soft tissue tumour (STT) grade. One hundred and twenty-nine lesions from 123 patients who underwent FDG-PET for primary staging (n = 79) or assessment of recurrence (n = 44) of STT were analyzed retrospectively. Histopathology was the reference standard for tumour grading. Absolute values and tumour-to-liver ratios of several standardized uptake value (SUV) parameters were correlated with tumour grading. At primary diagnosis SUV{sub max}, SUV{sub peak}, SUV{sub max}/SUV{sub liver} and SUV{sub peak}/SUV{sub liver} showed good correlation with tumour grade. SUV{sub peak} (area under the receiver-operating-characteristic, AUC-ROC: 0.82) and SUV{sub peak}/SUV{sub liver} (AUC-ROC: 0.82) separated best between low grade (WHO intermediate, grade 1 sarcoma, and low risk gastrointestinal stromal tumours, GISTs) and high grade (grade 2/3 sarcoma and intermediate/high risk GISTs) lesions: optimal threshold for SUV{sub peak}/SUV{sub liver} was 2.4, which resulted in a sensitivity of 79 % and a specificity of 81 %. At disease recurrence, the AUC-ROC was <0.75 for each parameter. A tumour SUV{sub peak} of at least 2.4 fold mean liver uptake predicts high grade histopathology with good diagnostic accuracy at primary staging. At disease recurrence, FDG-PET does not reliably separate high and low grade lesions. (orig.)

  16. CNS Vasculitis Associated with Waldenström Macroglobulinemia

    Riangwiwat, Tanawan; Wu, Chris Y.; Santos-Ocampo, Alberto S.; Liu, Randal J.


    Waldenström macroglobulinemia (WM) is an indolent B cell lymphoproliferative disorder with monoclonal IgM secretion. We present a patient with WM who presented with multifocal acute cortical ischemic strokes and was found to have central nervous system (CNS) vasculitis. Workup was negative for cryoglobulins and hyperviscosity syndrome. Immunosuppression with intravenous steroids and cyclophosphamide stabilized the patient's mental status and neurologic deficits. On followup over 7 years, patient gained independence from walking aids and experienced no recurrences of CNS vasculitis. To our knowledge, CNS vasculitis in a WM patient, in the absence of cryoglobulins, has not been reported. Immunosuppression is the preferred treatment. PMID:27818812

  17. CNS Vasculitis Associated with Waldenström Macroglobulinemia

    Tanawan Riangwiwat


    Full Text Available Waldenström macroglobulinemia (WM is an indolent B cell lymphoproliferative disorder with monoclonal IgM secretion. We present a patient with WM who presented with multifocal acute cortical ischemic strokes and was found to have central nervous system (CNS vasculitis. Workup was negative for cryoglobulins and hyperviscosity syndrome. Immunosuppression with intravenous steroids and cyclophosphamide stabilized the patient’s mental status and neurologic deficits. On followup over 7 years, patient gained independence from walking aids and experienced no recurrences of CNS vasculitis. To our knowledge, CNS vasculitis in a WM patient, in the absence of cryoglobulins, has not been reported. Immunosuppression is the preferred treatment.

  18. Promotion of Tumor-Initiating Cells in Primary and Recurrent Breast Tumors


    Currently we have shown that NF-κB is highly active in TICs isolated from different basal-like/ triple - negative cancer cell lines. Inhibition of NF-κB...phenotype, via its regulation of RelB. FDA-approved thiordiazine may be a treatment for basal-like/ triple - negative breast cancer via its ability to...Moreover, we have demonstrated that the EMT transcription factor, Snail, is markedly upregulated in recurrent mammary tumors, and that forced expression of

  19. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

    Sturm, Dominik; Orr, Brent A; Toprak, Umut H; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J; Balasubramanian, Gnanaprakash; Worst, Barbara C; Pajtler, Kristian W; Brabetz, Sebastian; Johann, Pascal D; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M; Remke, Marc; Phillips, Joanna J; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C; Schniederjan, Matthew J; Santi, Mariarita; Buccoliero, Anna M; Dahiya, Sonika; Kramm, Christof M; von Bueren, André O; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S; Taylor, Michael D; Jones, Chris; Jabado, Nada; Karajannis, Matthias A; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Ellison, David W; Korshunov, Andrey; Kool, Marcel


    Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

  20. c-erbB-2 protein overexpression and p53 immunoreaction in primary and recurrent breast cancer tissues.

    Shimizu, C; Fukutomi, T; Tsuda, H; Akashi-Tanaka, S; Watanabe, T; Nanasawa, T; Sugihara, K


    We investigated whether expression levels of c-erbB-2 and p53 proteins in breast cancer tissues differ in primary and metastatic lesions. Immunohistochemical staining or sandwich enzyme immunoassay was used to determine expression levels of c-erbB-2 and p53 proteins in 42 breast cancer samples from 21 patients. Estrogen (ER) and progesterone receptors (PgR) were also measured by enzyme immunoassay in each case. All patients had undergone radical surgery for primary tumors and surgical resection of asynchronous metastatic lesions. Thirteen patients (62%) were premenopausal and 14 (67%) received postoperative adjuvant therapies. Median disease-free survival time was 26 months (range, 5-104). The resected metastatic lesions included 1 in the liver, 3 in the lung, and 3 in the supraclavicular lymph nodes. The remaining 14 were local skin lesions. There was no difference in the positivity rate of c-erbB-2 (38%: 8/21) and p53 (39%: 7/18) expression between the primary tumors and the recurrent lesions. In addition, no discordant c-erbB-2 or p53 expression was observed between the primary tumors and their respective metastatic lesions. Positivity rates for ER and PgR were 50% (10/20) and 60% (12/20) for the primary tumors, but only 25% (5/20) and 30% (6/20) for the recurrent lesions, respectively (P = 0. 19 for ER and P = 0.11 for PgR). c-erbB-2 and p53 expression levels in breast cancer cells were almost unchanged as the disease progressed and/or in response to adjuvant therapies, regardless of the hormone receptor status. Copyright 2000 Wiley-Liss, Inc.

  1. Identification and validation of a multigene predictor of recurrence in primary laryngeal cancer.

    Elena Fountzilas

    Full Text Available PURPOSE: Local recurrence is the major manifestation of treatment failure in patients with operable laryngeal carcinoma. Established clinicopathological factors cannot sufficiently predict patients that are likely to recur after treatment. Additional tools are therefore required to accurately identify patients at high risk for recurrence. This study attempts to identify and independently validate gene expression models, prognostic of disease-free survival (DFS in operable laryngeal cancer. MATERIALS AND METHODS: Using Affymetrix U133A Genechips, we profiled fresh-frozen tumor tissues from 66 patients with laryngeal cancer treated locally with surgery. We applied Cox regression proportional hazards modeling to identify multigene predictors of recurrence. Gene models were then validated in two independent cohorts of 54 and 187 patients (fresh-frozen and formalin-fixed tissue validation sets, respectively. RESULTS: We focused on genes univariately associated with DFS (p<0.01 in the training set. Among several models comprising different numbers of genes, a 30-probe set model demonstrated optimal performance in both the training (log-rank, p<0.001 and 1(st validation (p=0.010 sets. Specifically, in the 1(st validation set, median DFS as predicted by the 30-probe set model, was 34 and 80 months for high- and low-risk patients, respectively. Hazard ratio (HR for recurrence in the high-risk group was 3.87 (95% CI 1.28-11.73, Wald's p=0.017. Testing the expression of selected genes from the above model in the 2(nd validation set, with qPCR, revealed significant associations of single markers, such as ACE2, FLOT1 and PRKD1, with patient DFS. High PRKD1 remained an unfavorable prognostic marker upon multivariate analysis (HR=2.00, 95% CI 1.28-3.14, p=0.002 along with positive nodal status. CONCLUSIONS: We have established and validated gene models that can successfully stratify patients with laryngeal cancer, based on their risk for recurrence. It seems

  2. Flavonoids and the CNS

    Jäger, Anna Katharina; Saaby, Lasse


    , sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABA(A)-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine...


    M. B. Kozlova


    Full Text Available The hormonal background was studied in 32 menopausal patients who had primary breast cancer (Stage III or its recurrence in the postoperative scar. The patients with the primary process, unlike those with a recurrence, were found to have increased adrenocortical cortisol-forming activity and changed thyroid homeostasis. In both types of the neoplastic process, the blood concentrations of estradi- ol, testosterone, prolactin, follicle-stimulating and luteinizing hormones were disturbed in a substantial number of cases; the distinc- tive feature of the primary process and its recurrence lies in the opposite direction. An association of individual differences in the con- centrations of estradiol and testosterone with the efficiency of neoadjuvant chemotherapy was analyzed in patients with recurrent can- cer.

  4. Actuarial risk of isolated CNS involvement in Ewing's sarcoma following prophylactic cranial irradiation and intrathecal methotrexate

    Trigg, M.E.; Makuch, R.; Glaubiger, D.


    Records of 154 patients with Ewing's sarcoma treated at the National Cancer Institute were reviewed to assess the incidence and risk of developing isolated central nervous system (CNS) Ewing's sarcoma. Sixty-two of the 154 patients had received CNS irradiation and intrathecal (i.t.) methotrexate as part of their initial therapy to prevent the occurrence of isolated CNS Ewing's sarcoma. The risk of developing isolate CNS Ewing's sarcoma was greatest within the first two years after diagnosis and was approximately 10%. The overall risk of CNS recurrence in the group of patients receiving DNS treatment was similar to the group receiving no therapy directed to the CNS. The occurrence of isolated CNS involvement was not prevented by the use of CNS irradiation and i.t. methotrexate. Because of a lack of efficacy to the CNS irradiation regimen, current treatment regimens do not include therapy directed to CNS.

  5. High serum YKL-40 levels in patients with primary breast cancer is related to short recurrence free survival

    Johansen, Julia S; Christensen, Ib Jarle; Riisbro, Rikke;


    YKL-40 is a growth factor for connective tissue cells and stimulates migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum YKL-40 in patients with metastatic breast cancer and colorectal cancer is associated with a poorer prognosis as compared to patients...... with normal serum YKL-40. In the present study we evaluated the associations of preoperative serum YKL-40 in 271 patients with primary breast cancer in relation to relapse-free survival and overall survival. The median follow-up time was 5.9 years. There were 77 relapses and 69 patients died. The median serum...... YKL-40 in patients with primary breast cancer at time of operation is only elevated in a small group of patients, but these patients have a shorter recurrence free interval. Further studies are required to determine the biological function of YKL-40 in breast cancer....

  6. Analysis of primary visual cortex in dementia with Lewy bodies indicates GABAergic involvement associated with recurrent complex visual hallucinations.

    Khundakar, Ahmad A; Hanson, Peter S; Erskine, Daniel; Lax, Nichola Z; Roscamp, Joseph; Karyka, Evangelia; Tsefou, Eliona; Singh, Preeti; Cockell, Simon J; Gribben, Andrew; Ramsay, Lynne; Blain, Peter G; Mosimann, Urs P; Lett, Deborah J; Elstner, Matthias; Turnbull, Douglass M; Xiang, Charles C; Brownstein, Michael J; O'Brien, John T; Taylor, John-Paul; Attems, Johannes; Thomas, Alan J; McKeith, Ian G; Morris, Christopher M


    Dementia with Lewy bodies (DLB) patients frequently experience well formed recurrent complex visual hallucinations (RCVH). This is associated with reduced blood flow or hypometabolism on imaging of the primary visual cortex. To understand these associations in DLB we used pathological and biochemical analysis of the primary visual cortex to identify changes that could underpin RCVH. Alpha-synuclein or neurofibrillary tangle pathology in primary visual cortex was essentially absent. Neurone density or volume within the primary visual cortex in DLB was also unchanged using unbiased stereology. Microarray analysis, however, demonstrated changes in neuropeptide gene expression and other markers, indicating altered GABAergic neuronal function. Calcium binding protein and GAD65/67 immunohistochemistry showed preserved interneurone populations indicating possible interneurone dysfunction. This was demonstrated by loss of post synaptic GABA receptor markers including gephyrin, GABARAP, and Kif5A, indicating reduced GABAergic synaptic activity. Glutamatergic neuronal signalling was also altered with vesicular glutamate transporter protein and PSD-95 expression being reduced. Changes to the primary visual cortex in DLB indicate that reduced GABAergic transmission may contribute to RCVH in DLB and treatment using targeted GABAergic modulation or similar approaches using glutamatergic modification may be beneficial.

  7. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A.; Thörn, Karolina; Cairns, Tina M.; Wegmann, Frank; Sattentau, Quentin J.; Eisenberg, Roselyn J.; Cohen, Gary H.; Harandi, Ali M.


    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes. PMID:28082979

  8. Maintenance pharmacotherapy for recurrent major depressive disorder in primary care: A 5-year follow-up study.

    Riihimäki, K; Vuorilehto, M; Isometsä, E


    Most practice guidelines recommend maintenance antidepressant treatment for recurrent major depressive disorder. However, the degree to which such guidance is actually followed in primary health care has remained obscure. We investigated the provision of maintenance antidepressant treatment within a representative primary care five-year cohort study. In the Vantaa Primary Care Depression Study, a stratified random sample of 1119 adult patients was screened for depression using the Prime-MD. Depressive and comorbid psychiatric disorders were diagnosed using SCID-I/P and SCID-II interviews. Of the 137 patients with depressive disorders, 82% completed the prospective five-year follow-up. A graphic life chart enabling evaluation of the longitudinal course of episodes plus duration of pharmacotherapies was used. In accordance with national guidelines, an indication for maintenance treatment was defined to exist after three or more lifetime major depressive episodes (MDEs); maintenance treatment was to commence four months after onset of full remission. Of the cohort patients, 34% (46/137) had three or more lifetime MDEs, thus indicating the requirement for maintenance pharmacotherapy. Of these, half (54%, 25/46) received maintenance treatment, for only 29% (489/1670) of the months indicated. In this cohort of depressed primary care patients, half of patients with indications for maintenance treatment actually received it, and only for a fraction of the time indicated. Antidepressant maintenance treatment for the prevention of recurrences is unlikely to be subject to large-scale actualization as recommended, which may significantly undermine the potential public health benefits of treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. CNS Tumors in Neurofibromatosis.

    Campian, Jian; Gutmann, David H


    Neurofibromatosis (NF) encompasses a group of distinct genetic disorders in which affected children and adults are prone to the development of benign and malignant tumors of the nervous system. The purpose of this review is to discuss the spectrum of CNS tumors arising in individuals with NF type 1 (NF1) and NF type 2 (NF2), their pathogenic etiologies, and the rational treatment options for people with these neoplasms. This article is a review of preclinical and clinical data focused on the treatment of the most common CNS tumors encountered in children and adults with NF1 and NF2. Although children with NF1 are at risk for developing low-grade gliomas of the optic pathway and brainstem, individuals with NF2 typically manifest low-grade tumors affecting the cranial nerves (vestibular schwannomas), meninges (meningiomas), and spinal cord (ependymomas). With the identification of the NF1 and NF2 genes, molecularly targeted therapies are beginning to emerge, as a result of a deeper understanding of the mechanisms underlying NF1 and NF2 protein function. As we enter into an era of precision oncology, a more comprehensive awareness of the factors that increase the risk of developing CNS cancers in affected individuals, coupled with a greater appreciation of the cellular and molecular determinants that maintain tumor growth, will undoubtedly yield more effective therapies for these cancer predisposition syndromes.

  10. Long-term follow-up results of primary and recurrent pigmented villonodular synovitis.

    Verspoor, Floortje G M; Zee, Aniek A G; Hannink, Gerjon; van der Geest, Ingrid C M; Veth, Rene P H; Schreuder, H W Bart


    Adequate documentation of the outcome of treatment of pigmented villonodular synovitis (PVNS) is sparse. Available case series show relatively short follow-up times and often combine locations or subtypes to increase patient numbers. This article describes the long-term follow-up of a single institution's large consecutive series of PVNS. Retrospectively, 107 PVNS patients were identified between 1985 and 2011 by searching pathology and radiology records. Treatment complications, recurrences and quality of life were evaluated. Most patients (85.2%) were primarily or secondarily treated at our institution. Both subtypes, localized PVNS [29 (27%)] and diffuse PVNS [75 (70%)] were represented. The knee was affected in 88% of patients. Treatments received were surgery, external beam radiotherapy, radiosynovectomy, targeted therapy, immunotherapy or combinations of these. Forty-nine (46%) patients had prior treatment elsewhere. The mean follow-up from diagnosis until last contact was 7.0 years (range 0.3-27.4) for localized PVNS and 14.5 years (range 1.1-48.7) for diffuse PVNS. The 1- and 5-year recurrence-free survival rates for diffuse PVNS were 69% and 32%, respectively. Quality of life, estimated by 36-item Short Form Health Survey (SF-36) scores, were not significantly different between localized and diffuse PVNS. However, both patient groups scored lower than the general population norms on the general health component (59.2 and 56.3, respectively, P PVNS increase with time. Long-term follow-up shows, particularly in diffuse PVNS, it is a continually recurring problem, and over time it becomes increasingly difficult to cure. The quality of life is decreased in patients with PVNS compared with the general population. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email:


    Nishiyama, Ryuichi; Kubota, Masashi; Kanno, Toru; Okada, Takashi; Higashi, Yoshihito; Yamada, Hitoshi


    A 69-year-old woman visited our hospital with a chief complaint of fever. Five years ago, she was diagnosed as ascending colon cancer and received right hemi-colectomy. One year later, local recurrence with right hydronephrosis was detected, and she received chemotherapy -4 cycles of modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab, and 12 cycles of fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab- for two years. Local recurrence and right hydronephrosis disappeared on positron emission tomography performed 4 years postoperatively. This time, abdominal computed tomography for investigation of fever showed a relapse of right hydronephrosis and pyonephrosis. Cystoscopy revealed non-papillary tumor from the right ureteral orifice. Pelvic magnetic resonance imaging showed multiple tumors in the right ureter, and the distal lesion projecting into the bladder. After the general condition became well by right nephrostomy for infection control, transurethral resection of bladder tumor was performed. Histological examination of the specimen revealed a metastatic tubular adenocarcinoma (colon origin). Although right nephrectomy was performed for pyonephrosis control, she died of local progression of ascending colon cancer 10 months after first visit. Intraluminal ureteral progression of carcinoma originating from organs other than urinary tract is very rare. To our knowledge, this is the 9th report in the English or Japanese literature. In this case we could not rule out primary ureteral cancer preoperatively, and histological examination revealed intraluminal ureteral dissemination of ascending colon cancer.

  12. Recurrence of primary hyperoxaluria after kidney transplantation: the report of two cases

    SHANG Ming-hua; JUN Hua; FAN Yu; ZHANG Zheng; WANG Ling; GU Li-jie; HE Zhi-yan; YUAN Wei-jie


    @@ Primary hyperoxaluria (PH) is a rare autosomal recessive disorder of glyoxylate metabolism in which specific hepatic enzyme deficiencies result in overproduction of oxalate. Because oxalate is excreted exclusively by the kidney, hyperoxaluria leads to calcium oxalate nephrolithiasis, nephrocalcinosis, and renal failure.

  13. Recurrent and persistent respiratory tract viral infections in patients with primary hypogammaglobulinemia.

    Kainulainen, Leena; Vuorinen, Tytti; Rantakokko-Jalava, Kaisu; Osterback, Riikka; Ruuskanen, Olli


    The occurrence of respiratory tract viral infections in patients with primary hypogammaglobulinemia has not been studied. We conducted a prospective 12-month follow-up study of respiratory tract infections in 12 adult patients with primary hypogammaglobulinemia. Nasal swab samples and induced sputum samples were taken at the onset of acute respiratory tract infection and every 3 months thereafter. Samples were tested for bacteria and viruses. PCR tests were performed for 15 respiratory tract viruses. In case the results for rhinovirus were positive, follow-up nasal swab samples were taken every 2 weeks until rhinoviral PCR results became negative. Patients completed symptom diaries, which were collected every month. The spouses of the patients served as healthy control subjects. During the 12-month period, the 12 patients had 65 episodes of acute respiratory tract infections, and the 11 spouses had 12 acute episodes (P < .001). Respiratory tract viruses were found in sputum in 54% of the infections. Rhinovirus was the most common virus. In more than half of our patients, rhinoviral PCR results stayed positive for more than 2 months. The most long-acting persistence with the same rhinovirus was 4 months. Despite adequate immunoglobulin replacement therapy, patients with primary hypogammaglobulinemia have increased susceptibility to respiratory tract viral infections. Rhinoviral infections are frequent and prolonged. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.


    Hoti Lal


    Full Text Available Primary Squamous Cell Carcinoma in the kidney is a rare malignant neoplasm associated with nephrolithiasis, typically monobacterial pyonephrosis and rarely Xanthogranulomatous pyelonephritis. It is an aggressive disease with a poor prognosis mostly due to lack of presenting clinical features like a palpable mass, gross haematuria and pain. We report a case presenting with renal calculus and pyonephrosis managed initially with percutaneous nephrostomy followed by nephrectomy due to complete loss of renal function. Histopathological evaluation revealed poorly differentiated squamous cell carcinoma which is managed by chemotherapy, although initially beneficial, patients later develop disseminated metastatic disease which holds a poor prognosis.

  15. Recurrent breast cancer: presentation, diagnosis, and treatment.

    Jardines, L; Callans, L S; Torosian, M H


    Patients must be followed up closely after primary therapy for invasive breast cancer so that locoregional recurrences can be detected early. Once a recurrence has been detected, a thorough evaluation is indicated to exclude distant metastatic disease. If none is found, the patient may be a candidate for aggressive surgical intervention to render the patient disease-free. If distant disease is found, certain sites, such as the CNS or long bones, may warrant aggressive therapy because failure to treat these sites may lead to excessive morbidity. In most situations, patients with distant disease are treated with palliative measures. In selected instances, however, patients with metastatic breast cancer are candidates for aggressive intervention, including pulmonary or liver resection or high-dose chemotherapy in combination with autologous bone marrow transplantation, to rid the patient of the disease.

  16. Patterns of recurrence and second primary lung cancer in early-stage lung cancer survivors followed with routine computed tomography surveillance.

    Lou, Feiran; Huang, James; Sima, Camelia S; Dycoco, Joseph; Rusch, Valerie; Bach, Peter B


    At present, there is no consensus on the optimal strategy for follow-up care after curative resection for lung cancer. We sought to understand the patterns of recurrence and second primary lung cancer, and their mode of detection, after resection for early-stage non-small cell lung cancer in patients who were followed by routine surveillance computed tomography scan. We reviewed the outcomes of consecutive patients who underwent resection for early-stage non-small cell lung cancer at Memorial Sloan-Kettering Cancer Center between 2004 and 2009. A total of 1294 consecutive patients with early-stage non-small cell lung cancer underwent resection. The median length of follow-up was 35 months. Recurrence was diagnosed in 257 patients (20%), and second primary lung cancer was diagnosed in 91 patients (7%). The majority of new primary cancers (85 [93%]) were identified by scheduled routine computed tomography scan, as were a smaller majority of recurrences (157 [61%]). During the first 4 years after surgery, the risk of recurrence ranged from 6% to 10% per person-year but decreased thereafter to 2%. Conversely, the risk of second primary lung cancer ranged from 3% to 6% per person-year and did not diminish over time. Additional testing after false-positive surveillance computed tomography scan results was performed for 329 patients (25%), but only 4 of these patients (0.3%) experienced complications as a result of subsequent invasive diagnostic procedures. Almost all second primary cancers and the majority of recurrences were detected by post-therapeutic surveillance computed tomography scan. The risk of recurrence for early-stage non-small cell lung cancer survivors persisted during the first 4 years after resection, and vigilance in surveillance should be maintained. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  17. The predictive value of preoperative {sup 18}F-fluorodeoxyglucose PET for postoperative recurrence in patients with localized primary gastrointestinal stromal tumour

    Miyake, Kanae Kawai; Nakamoto, Yuji; Togashi, Kaori [Kyoto University Hospital, Department of Diagnostic Imaging and Nuclear Medicine, Kyoto (Japan); Mikami, Yoshiki [Kyoto University Hospital, Department of Diagnostic Pathology, Kyoto (Japan); Kumamoto University Hospital, Department of Diagnostic Pathology, Kumamoto (Japan); Tanaka, Shiro [Kyoto University, Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto (Japan); Higashi, Tatsuya [Shiga Medical Center Research Institute, Shiga (Japan); Tadamura, Eiji [Sakazaki Clinic, Department of Radiology, Kyoto (Japan); Saga, Tsuneo [National Institute of Radiological Sciences, Dianostic Imaging Group, Molecular Imaging Center, Chiba (Japan); Minami, Shunsuke [Shiga Medical Center for Adults, Department of Radiology, Shiga (Japan)


    To assess the potential value of preoperative {sup 18}F-FDG PET to predict postoperative recurrence of solitary localized primary gastrointestinal stromal tumour (GIST) after radical resection. A total of 46 patients with primary GIST who received preoperative {sup 18}F-FDG PET and underwent complete resection without neoadjuvant therapy were retrospectively studied. PET findings, including ring-shaped uptake and intense uptake, were compared with Joensuu risk grades using Fisher's exact test. The prognostic value of the preoperative clinico-imaging variables - age ≥60 years, male, ring-shaped uptake, intense uptake, tumour size >5 cm, heterogeneous CT attenuation and lower gastrointestinal origin - and Joensuu high risk for recurrence-free survival was evaluated using log-rank test and multivariate Cox regression analysis. Ring-shaped uptake and intense uptake were significantly associated with Joensuu high risk. Univariate analysis showed that ring-shaped uptake, intense uptake, size >5 cm and Joensuu high risk were significantly associated with inferior recurrence-free survival. Multivariate analysis showed that ring-shaped uptake (P = 0.004) and Joensuu high risk (P = 0.021) were independent adverse prognostic factors of postoperative recurrence. Ring-shaped uptake on preoperative {sup 18}F-FDG PET may be a potential predictor of postoperative tumour recurrence of localized primary GISTs. (orig.)

  18. CNS regulation of appetite.

    Harrold, Joanne A; Dovey, Terry M; Blundell, John E; Halford, Jason C G


    This article reviews the regulation of appetite from a biopsychological perspective. It considers psychological experiences and peripheral nutritional systems (both episodic and tonic) and addresses their relationship with the CNS networks that process and integrate their input. Whilst such regulatory aspects of obesity focus on homeostatic control mechanisms, in the modern environment hedonic aspects of appetite are also critical. Enhanced knowledge of the complexity of appetite regulation and the mechanisms that sustain obesity indicate the challenge presented by management of the obesity epidemic. Nonetheless, effective control of appetite expression remains a critical therapeutic target for weight management. Currently, strategies which utilise a combination of agents to target both homeostatic and hedonic control mechanisms represent the most promising approaches. This article is part of a Special Issue entitled 'Central Control of Food Intake'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Species distribution and in vitro antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis.

    Hamza, O.J.; Matee, M.I.N.; Moshi, M.J.; Simon, E.N.; Mugusi, F.; Mikx, F.H.M.; Palenstein Helderman, W.H. van; Rijs, A.J.M.M.; Ven, A.J.A.M. van der; Verweij, P.E.


    BACKGROUND: In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis. METHODS: A total of 296 clinical oral yeasts were isolated from 292 HIV-infected patients wit

  20. Long-term follow-up evaluation of chronic pain after endoscopic total extraperitoneal repair of primary and recurrent inguinal hernia

    A.E.M. van der Pool (Anne); J.J. Harlaar (Jaap); P.Th. den Hoed (Pieter); W.F. Weidema (Wibo); R.N. van Veen (Ruben)


    textabstractBackground Long-term data on chronic pain after endoscopic total extraperitoneal (TEP) hernia repair are hardly available. Methods Between January 1997 and December 1998, 416 patients with consecutive primary and recurrent inguinal hernia underwent endoscopic TEP hernia repair. Long-term

  1. Derivation and characterization of matched cell lines from primary and recurrent serous ovarian cancer

    Létourneau Isabelle J


    Full Text Available Abstract Background Cell line models have proven to be effective tools to investigate a variety of ovarian cancer features. Due to the limited number of cell lines, particularly of the serous subtype, the heterogeneity of the disease, and the lack of cell lines that model disease progression, there is a need to further develop cell line resources available for research. This study describes nine cell lines derived from three ovarian cancer cases that were established at initial diagnosis and at subsequent relapse after chemotherapy. Methods The cell lines from three women diagnosed with high-grade serous ovarian cancer (1369, 2295 and 3133 were derived from solid tumor (TOV and ascites (OV, at specific time points at diagnosis and relapse (R. Primary treatment was a combination of paclitaxel/carboplatin (1369, 3133, or cisplatin/topotecan (2295. Second line treatment included doxorubicin, gemcitabine and topotecan. In addition to molecular characterization (p53, HER2, the cell lines were characterized based on cell growth characteristics including spheroid growth, migration potential, and anchorage independence. The in vivo tumorigenicity potential of the cell lines was measured. Response to paclitaxel and carboplatin was assessed using a clonogenic assay. Results All cell lines had either a nonsense or missense TP53 mutations. The ability to form compact spheroids or aggregates was observed in six of nine cell lines. Limited ability for migration and anchorage independence was observed. The OV3133(R cell line, formed tumors at subcutaneous sites in SCID mice. Based on IC50 values and dose response curves, there was clear evidence of acquired resistance to carboplatin for TOV2295(R and OV2295(R2 cell lines. Conclusion The study identified nine new high-grade serous ovarian cancer cell lines, derived before and after chemotherapy that provides a unique resource for investigating the evolution of this common histopathological subtype of ovarian

  2. Primary EBV-positive Hodgkin's lymphoma of the CNS under azathioprine treatment. Case report and review of the literature

    Henkenberens, Christoph; Christiansen, Hans [Medizinische Hochschule Hannover, Klinik fuer Strahlentherapie und Spezielle Onkologie, Hannover (Germany); Franzke, Anke [Medizinische Hochschule Hannover, Klinik fuer Haematologie, Haemostaseologie, Onkologie und Stammzelltransplantation, Hannover (Germany); Raab, Peter [Medizinische Hochschule Hannover, Institut fuer Diagnostische und Interventionelle Neuroradiologie, Hannover (Germany); Oschlies, Ilske; Klapper, Wolfram [Universitaetsklinikum Schleswig-Holstein, Institut fuer Pathologie, Sektion Haematopathologie, Kiel (Germany)


    Retrospective and prospective cohort studies suggest that central nervous system involvement occurs in approximately 0.5 % of patients with advanced Hodgkin's lymphoma. The isolated primary intracranial manifestation of Hodgkin's lymphoma is an extremely rare finding, with few cases reported in the literature. Little is known about the optimal treatment and prognosis of these tumors. Here, we present a case report with a review of the literature. A 47-year-old Caucasian man with persistent frontal headache and unspecific vertigo for half a month was diagnosed with nodular space-occupying lesions in the cerebellum. His medical history included multiple sclerosis, which was treated for 20 years with the immunosuppressive drug azathioprine. Further staging revealed no additional lesions suspected of being malignant. The patient underwent total tumor resection. Immunohistopathological examination showed Epstein-Barr virus-associated classic Hodgkin's lymphoma. Diagnostic bone marrow punction excluded lymphoma involvement of the bone marrow. The patient had no B symptoms. Consequently, the patient was classified as having stage I{sub E}A disease according to the Modified Ann Arbor Classification of Hodgkin Lymphoma and received systemic chemotherapy followed by radiation therapy for the former cerebellar tumor region. He was in complete clinical remission at the last follow-up 9 months after the initial diagnosis. This case report and literature review suggest that multimodal treatment leads to a remarkable clinical outcome in Hodgkin's lymphoma with intracranial involvement. (orig.) [German] Retrospektive und prospektive Kohortenstudien deuten daraufhin, dass eine Beteiligung des zentralen Nervensystems (ZNS) in etwa bei 0,5 % der Patienten mit fortgeschrittenem Hodgkin-Lymphom auftritt. Die isoliert primaer intrakranielle Manifestation des Hodgkin-Lymphoms ist extrem selten, mit wenigen bisher bekannten Faellen. Wenig ist auch ueber die optimale

  3. Propranolol associated with endoscopic band ligation reduces recurrence of esophageal varices for primary prophylaxis of variceal bleeding: a randomized-controlled trial.

    Bonilha, Danielle Queiroz; Lenz, Luciano; Correia, Lucianna Motta; Rodrigues, Rodrigo Azevedo; de Paulo, Gustavo Andrade; Ferrari, Angelo Paulo; Della Libera, Ermelindo


    The aim of this study was to compare the recurrence of esophageal varices (EVs) after endoscopic band ligation (EBL) associated with propranolol (PP) versus EBL alone. Sixty-six cirrhotic outpatients (EBL group, n=32 and EBL+PP group, n=34) with high-risk EVs without previous bleeding were studied. The primary outcome was recurrence of EV. The secondary outcomes were EV eradication, bleeding before EV eradication, mortality, and adverse events. Demographic characteristics and the initial endoscopic findings were similar. EV eradication was achieved in all patients. Three patients presented gastrointestinal bleeding before variceal eradication, two in the EBL group and one in the EBL+PP group (P=0.13). Six patients died (liver failure), two in the EBL group and four in the EBL+PP group (P=0.27). Twelve (38%) patients in the EBL group and three (9%) patients in the EBL+PP group had variceal recurrence. The risk of recurrence of EVs after eradication was significantly higher among patients in the EBL group (P=0.003). EBL alone and EBL+PP were effective in the primary prophylaxis of bleeding from EVs in cirrhotic patients (EV eradication, bleeding before EV eradication, mortality, and adverse events were similar in both groups). However, variceal recurrence was lower in the EBL+PP group than band ligation alone.

  4. Innate Interferons Regulate CNS Inflammation

    Dieu, Ruthe; Khorooshi, Reza M. H.; Mariboe, Anne

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) whose pathology is characterised by demyelination and axonal damage. This results from interplay between CNS-resident glia, infiltrating leukocytes and a plethora of cytokines and chemokines. Currently, ...

  5. Immunohistochemical comparison of CD5, lambda, and kappa expression in primary and recurrent buccal mucosa-associated lymphoid tissue (MALT) lymphomas.

    Tanaka, Toshiaki; Kitabatake, Kenichirou; Iino, Mituyoshi; Goto, Kaoru


    Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal marginal zone B-cell lymphoma and is a distinct subtype of non-Hodgkin's lymphoma.Primary MALT lymphomas can also occur in the oral cavity, although their appearance in this location is rare. The neoplastic cells of which MALT lymphomas are composed express B-cell antigens and show monotypic immunoglobulin expression with light-chain restriction.Although neoplastic MALT lymphoma cells do not express CD5, previous studies have shown that CD5 positive MALT lymphomas are more prone to dissemination than those that do not express CD5. Moreover, there are some reports that describe kappa- and lambda- dual light chain expression in B cell malignant neoplasms.A 66-year-old Japanese woman with swelling of the right buccal mucosa was referred to our hospital. The lesion was excised and was pathologically diagnosed as a MALT lymphoma tumor with a t(11;18)(q21;q21) chromosome translocation.Swelling of the right buccal mucosa recurred 2 years later. The recurrent tumor was then excised and pathologically diagnosed as MALT lymphoma.Immunohistochemical examination of CD5, lambda, and kappa expressions revealed that the primary tumor was positive for CD5, kappa, and lambda, but the recurrent tumor was weakly positive for CD5 and kappa.With respect to lambda positivity, the recurrent tumor showed negativity.Our study suggests that immunohistochemical expression of CD5, kappa, and lambda in oral MALT lymphoma have the risk of recurrence.We first described the recurrence of CD5 positive MALT lymphoma in the oral cavity and compared the immunohistochemical expressions of CD5, lambda, and kappa between the primary and recurrent tumors.

  6. Flavonoids and the CNS

    Anna K. Jäger


    Full Text Available Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on their structure. Flavonoids are present in food and medicinal plants and are thus consumed by humans. They are found in plants as glycosides. Before oral absorption, flavonoids undergo deglycosylation either by lactase phloridzin hydrolase or cytosolic β-glucocidase. The absorbed aglycone is then conjugated by methylation, sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABAA-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine oxidase A or B, thereby working as anti-depressants or to improve the conditions of Parkinson’s patients. Flavanols, flavanones and anthocyanidins have protective effects preventing inflammatory processes leading to nerve injury. Flavonoids seem capable of influencing health and mood.

  7. Treatment Options for Primary CNS Lymphoma

    ... reflexes work. This may also be called a neuro exam or a neurologic exam. Slit-lamp eye ... Websites POLICIES Accessibility Comment Policy Disclaimer FOIA Privacy & Security Reuse & Copyright Syndication Services Website Linking U.S. Department ...

  8. Treatment Option Overview (Primary CNS Lymphoma)

    ... reflexes work. This may also be called a neuro exam or a neurologic exam. Slit-lamp eye ... Websites POLICIES Accessibility Comment Policy Disclaimer FOIA Privacy & Security Reuse & Copyright Syndication Services Website Linking U.S. Department ...

  9. Plasma TNF-alpha levels are higher in early pregnancy in patients with secondary compared with primary recurrent miscarriage

    Goegebeur, Yuri; Psiosik, Zofia; Klitkou, Louise


    Specific pro-inflammatory cytokine profiles in plasma may characterize women with recurrent miscarriage (RM) but the dynamics of the cytokine profiles with progressing pregnancy is largely unknown.......Specific pro-inflammatory cytokine profiles in plasma may characterize women with recurrent miscarriage (RM) but the dynamics of the cytokine profiles with progressing pregnancy is largely unknown....

  10. [18F]fluoroethylcholine-PET/CT imaging for radiation treatment planning of recurrent and primary prostate cancer with dose escalation to PET/CT-positive lymph nodes

    Wahl Andreas


    Full Text Available Abstract Background At present there is no consensus on irradiation treatment volumes for intermediate to high-risk primary cancers or recurrent disease. Conventional imaging modalities, such as CT, MRI and transrectal ultrasound, are considered suboptimal for treatment decisions. Choline-PET/CT might be considered as the imaging modality in radiooncology to select and delineate clinical target volumes extending the prostate gland or prostate fossa. In conjunction with intensity modulated radiotherapy (IMRT and imaged guided radiotherapy (IGRT, it might offer the opportunity of dose escalation to selected sites while avoiding unnecessary irradiation of healthy tissues. Methods Twenty-six patients with primary (n = 7 or recurrent (n = 19 prostate cancer received Choline-PET/CT planned 3D conformal or intensity modulated radiotherapy. The median age of the patients was 65 yrs (range 45 to 78 yrs. PET/CT-scans with F18-fluoroethylcholine (FEC were performed on a combined PET/CT-scanner equipped for radiation therapy planning. The majority of patients had intermediate to high risk prostate cancer. All patients received 3D conformal or intensity modulated and imaged guided radiotherapy with megavoltage cone beam CT. The median dose to primary tumours was 75.6 Gy and to FEC-positive recurrent lymph nodal sites 66,6 Gy. The median follow-up time was 28.8 months. Results The mean SUVmax in primary cancer was 5,97 in the prostate gland and 3,2 in pelvic lymph nodes. Patients with recurrent cancer had a mean SUVmax of 4,38. Two patients had negative PET/CT scans. At 28 months the overall survival rate is 94%. Biochemical relapse free survival is 83% for primary cancer and 49% for recurrent tumours. Distant disease free survival is 100% and 75% for primary and recurrent cancer, respectively. Acute normal tissue toxicity was mild in 85% and moderate (grade 2 in 15%. No or mild late side effects were observed in the majority of patients (84%. One patient had

  11. A Phase I Study of the Combination of Sorafenib With Temozolomide and Radiation Therapy for the Treatment of Primary and Recurrent High-Grade Gliomas

    Den, Robert B., E-mail: [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Kamrava, Mitchell [Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland (United States); Sheng, Zhi [Howard Hughes Medical Institute, Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts (United States); Werner-Wasik, Maria; Dougherty, Erin; Marinucchi, Michelle [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Lawrence, Yaacov R. [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Center for Translational Research in Radiation Oncology, Sheba Medical Center (Israel); Hegarty, Sarah; Hyslop, Terry [Department of Biostatistics, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Andrews, David W.; Glass, Jon [Department of Neurosurgery, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Friedman, David P. [Department of Radiology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Green, Michael R. [Howard Hughes Medical Institute, Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts (United States); Camphausen, Kevin [Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland (United States); Dicker, Adam P. [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)


    Purpose: Despite recent advances in the management of high-grade and recurrent gliomas, survival remains poor. Antiangiogenic therapy has been shown to be efficacious in the treatment of high-grade gliomas both in preclinical models and in clinical trials. We sought to determine the safety and maximum tolerated dose of sorafenib when combined with both radiation and temozolomide in the primary setting or radiation alone in the recurrent setting. Methods and Materials: This was a preclinical study and an open-label phase I dose escalation trial. Multiple glioma cell lines were analyzed for viability after treatment with radiation, temozolomide, or sorafenib or combinations of them. For patients with primary disease, sorafenib was given concurrently with temozolomide (75 mg/m{sup 2}) and 60 Gy radiation, for 30 days after completion of radiation. For patients with recurrent disease, sorafenib was combined with a hypofractionated course of radiation (35 Gy in 10 fractions). Results: Cell viability was significantly reduced with the combination of radiation, temozolomide, and sorafenib or radiation and sorafenib. Eighteen patients (11 in the primary cohort, 7 in the recurrent cohort) were enrolled onto this trial approved by the institutional review board. All patients completed the planned course of radiation therapy. The most common toxicities were hematologic, fatigue, and rash. There were 18 grade 3 or higher toxicities. The median overall survival was 18 months for the entire population. Conclusions: Sorafenib can be safely combined with radiation and temozolomide in patients with high-grade glioma and with radiation alone in patients with recurrent glioma. The recommended phase II dose of sorafenib is 200 mg twice daily when combined with temozolomide and radiation and 400 mg with radiation alone. To our knowledge, this is the first publication of concurrent sorafenib with radiation monotherapy or combined with radiation and temozolomide.

  12. In vitro activity of cadazolid against Clostridium difficile strains isolated from primary and recurrent infections in Stockholm, Sweden.

    Rashid, Mamun-Ur; Lozano, Helena Martinez; Weintraub, Andrej; Nord, Carl Erik


    One hundred thirty-three Clostridium difficile strains were collected from 71 patients and analyzed for the presence of C. difficile toxin B by the cell cytotoxicity neutralization assay, genes for toxin A, toxin B, binary toxin and TcdC deletion by PCR. All strains were also PCR-ribotyped and analyzed for sporulation frequency. The MICs of the isolates were determined against cadazolid and seven other antimicrobial agents by the agar dilution method. All isolates were positive for toxin B by the cell cytotoxicity neutralization assay. One hundred fourteen isolates were positive for toxin A and B and 16 isolates were positive for toxin A, toxin B and binary toxin by PCR. Three isolates were negative for toxin A but positive for toxin B. Thirty-three different ribotypes were identified. No strain of ribotype 027 was found. No differences in sporulation were noticed between the primary and recurrent isolates. All 133 isolates were sensitive to cadazolid (0.064-0.5 mg/l), fidaxomicin (0.008-0.125 mg/l), metronidazole (0.125-2 mg/l), vancomycin (0.125-1 mg/l) and tigecycline (0.032-0.25 mg/l). Three isolates were resistant to linezolid (8 mg/l), 15 isolates were resistant to moxifloxacin (8-32 mg/l) and 103 isolates were resistant to clindamycin (8-256 mg/l). No association between toxins A, B and binary toxin, ribotypes or the sporulation and the sensitivity to cadazolid could be found. Cadazolid has a potent in vitro activity against C. difficile.

  13. Environmental Causes of CNS Maldevelopment

    J Gordon Millichap


    Full Text Available Developmental processes and the effects of toxic agents in the environment that alter CNS growth and maturation are reviewed by a researcher in the Department of OB/GYN, University of Rochester Medical Center, Rochester, NY.

  14. What is the role of postoperative re-irradiation in recurrent and second primary squamous cell cancer of head and neck? A literature review according to PICO criteria.

    Merlotti, Anna; Mazzola, Rosario; Alterio, Daniela; Alongi, Filippo; Bacigalupo, Almalina; Bonomo, Pierluigi; Maddalo, Marta; Russi, Elvio Grazioso; Orlandi, Ester


    Re-irradiation has been increasingly offered as a potential effective treatment for head and neck squamous cell carcinoma (HNSCC) loco-regional recurrence as well as second primary tumor in previously irradiated area. This review focused on the role of postoperative re-irradiation (POreRT) in terms of feasibility, toxicity and long-term outcomes in HNSCC patients. The key issue for the research was formulated in two questions according to the PICO (population, intervention, control, and outcomes) criteria. A total of 16 publications met the inclusion criteria for a total of 919 patients; in 522 patients POreRT was performed. POreRT in recurrent and second primary HNSCC seems to be feasible in highly selected patients with the intent to guarantee an acceptable LC compared to surgery alone. The optimal RT schedule remains unclear due to the heterogeneity of literature data.

  15. Simultaneous [18F]FDG-PET/MRI: Correlation of Apparent Diffusion Coefficient (ADC and Standardized Uptake Value (SUV in Primary and Recurrent Cervical Cancer.

    P Brandmaier

    Full Text Available Previous non-simultaneous PET/MR studies have shown heterogeneous results about the correlation between standardized uptake values (SUVs and apparent diffusion coefficients (ADCs. The aim of this study was to investigate correlations in patients with primary and recurrent tumors using a simultaneous PET/MRI system which could lead to a better understanding of tumor biology and might play a role in early response assessment.We included 31 patients with histologically confirmed primary (n = 14 or recurrent cervical cancer (n = 17 who underwent simultaneous whole-body 18F-FDG-PET/MRI comprising DWI. Image analysis was performed by a radiologist and a nuclear physician who identified tumor margins and quantified ADC and SUV. Pearson correlations were calculated to investigate the association between ADC and SUV.92 lesions were detected. We found a significant inverse correlation between SUVmax and ADCmin (r = -0.532, p = 0.05 in primary tumors as well as in primary metastases (r = -0.362, p = 0.05 and between SUVmean and ADCmin (r = -0.403, p = 0.03. In recurrent local tumors we found correlations for SUVmax and ADCmin (r = -0.747, p = 0.002 and SUVmean and ADCmin (r = -0.773, p = 0.001. Associations for recurrent metastases were not significant (p>0.05.Our study demonstrates the feasibility of fast and reliable measurement of SUV and ADC with simultaneous PET/MRI. In patients with cervical cancer we found significant inverse correlations for SUV and ADC which could play a major role for further tumor characterization and therapy decisions.

  16. Molecular characterization of permanent cell lines from primary, metastatic and recurrent malignant peripheral nerve sheath tumors (MPNST) with underlying neurofibromatosis-1.

    Fang, Yuqiang; Elahi, Abul; Denley, Ryan C; Rao, Pulivarthi H; Brennan, Murray F; Jhanwar, Suresh C


    Malignant peripheral nerve sheath tumors (MPNSTs) develop in patients with underlying NF1, and usually arise as a result of malignant transformation of a pre-existing plexiform neurofibroma. The clonal cytogenetic abnormalities reported in primary MPNST include complex karyotypes with chromosome numbers in the triploid or tetraploid range with recurrent abnormalities of several chromosomes including losses or imbalances. As a prelude to cell biological, pharmacological, and functional studies to investigate pathways and gene(s) associated with multistep tumorigenesis, which includes progression, metastasis and resistance to therapy in MPNST, detailed molecular cytogenetic and genetic analyses of cell lines from primary, metastatic and recurrent MPNST with underlying NF1 disorder have been performed. The clonal cytogenetic abnormalities detected in the primary tumor cell line were similar to those observed in primary cultures of this tumor. Due to the complexity of the rearrangements seen by G-banded karyotype analysis, further characterization of the clonal abnormalities in these three cell lines was performed by molecular cytogenetic techniques, including CGH and SKY. CGH analysis detected recurrent deletions of 9p, 12q21-q32, complete losses of the X-chromosome, and gains of the chromosomal segment 17q25 in all three cell lines. SKY analysis detected extensive clonal abnormalities in these cell lines. The nature and the alterations of the cell cycle regulators, particularly those associated with G1-S checkpoints and known to be deregulated in MPNST, were studied. These cell cycle regulators included those associated with Rb1-cyclin D1 and the p53 pathways. The findings are consistent with the argument that an imbalance between the cyclin activators of CDKs and inhibitory proteins such as p16 result in uncontrollable proliferation in the cell lines, associated with progression of the disease. LOH and expression of the p53 gene in metastatic and recurrent cell

  17. Species distribution and in vitro antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis

    Rijs Antonius JMM


    Full Text Available Abstract Background In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis. Methods A total of 296 clinical oral yeasts were isolated from 292 HIV-infected patients with oropharyngeal candidiasis at the Muhimbili National Hospital, Dar es Salaam, Tanzania. Identification of the yeasts was performed using standard phenotypic methods. Antifungal susceptibility to fluconazole, itraconazole, miconazole, clotrimazole, amphotericin B and nystatin was assessed using a broth microdilution format according to the guidelines of the Clinical and Laboratory Standard Institute (CLSI; M27-A2. Results Candida albicans was the most frequently isolated species from 250 (84.5% patients followed by C. glabrata from 20 (6.8% patients, and C. krusei from 10 (3.4% patients. There was no observed significant difference in species distribution between patients with primary and recurrent oropharyngeal candidiasis, but isolates cultured from patients previously treated were significantly less susceptible to the azole compounds compared to those cultured from antifungal naïve patients. Conclusion C. albicans was the most frequently isolated species from patients with oropharyngeal candidiasis. Oral yeast isolates from Tanzania had high level susceptibility to the antifungal agents tested. Recurrent oropharyngeal candidiasis and previous antifungal therapy significantly correlated with reduced susceptibility to azoles antifungal agents.

  18. Serum levels of GFAP and EGFR in primary and recurrent high-grade gliomas: correlation to tumor volume, molecular markers, and progression-free survival.

    Kiviniemi, Aida; Gardberg, Maria; Frantzén, Janek; Parkkola, Riitta; Vuorinen, Ville; Pesola, Marko; Minn, Heikki


    Our aim was to study the association of two potential serum biomarkers glial fibrillary acidic protein (GFAP) and epidermal growth factor receptor (EGFR) with prognostic markers such as IDH1 mutation, tumor burden, and survival in patients with high-grade gliomas (HGG). Additionally, our objective was to evaluate the potential of serum EGFR as a surrogate marker for EGFR status in the tumor. Pre-operative serum samples were prospectively collected from patients with primary (n = 17) or recurrent (n = 10) HGG. Serum GFAP and EGFR levels were determined by ELISA and studied for correlation with molecular markers including EGFR amplification, tumor volume in contrast-enhanced T1-weighted MRI, and progression-free survival (PFS). Pre-operative serum GFAP level of ≥0.014 ng/ml was 86 % sensitive and 85 % specific for the diagnosis of glioblastoma. High GFAP was related to the lack of IDH1 mutation (P = 0.016), high Ki67 proliferation index (P < 0.001), and poor PFS (HR 5.9, CI 1.2-29.9, P = 0.032). Serum GFAP correlated with enhancing tumor volume in primary (r = 0.64 P = 0.005), but also in recurrent HGGs (r = 0.76 P = 0.011). In contrast, serum EGFR levels did not differ between HGG patients and 13 healthy controls, and were not related to EGFR status in the tumor. We conclude that high serum GFAP associates with IDH1 mutation-negative HGG, and poor PFS. Correlation with tumor burden in recurrent HGG implicates the potential of serum GFAP for detection of tumor recurrence. Our results suggest that circulating EGFR is not derived from glioma cells and cannot be used as a marker for EGFR status in the tumor.

  19. Interstitial Photodynamic Therapy in Treating Patients With Recurrent Head and Neck Cancer


    Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma

  20. Genetic models for CNS inflammation

    Owens, T; Wekerle, H; Antel, J


    The use of transgenic technology to over-express or prevent expression of genes encoding molecules related to inflammation has allowed direct examination of their role in experimental disease. This article reviews transgenic and knockout models of CNS demyelinating disease, focusing primarily on ...

  1. Basic Concepts of CNS Development.

    Nowakowski, R. S.


    The goals of this review are to: (1) provide a set of concepts to aid in the understanding of complex processes which occur during central nervous system (CNS) development; (2) illustrate how they contribute to our knowlege of adult brain anatomy; and (3) delineate how modifications of normal developmental processes may affect the structure and…

  2. Stability of glycoprotein gene sequences of herpes simplex virus type 2 from primary to recurrent human infection, and diversity of the sequences among patients attending an STD clinic


    Background Herpes simplex virus type 2 (HSV-2) is sexually transmitted, leading to blisters and ulcers in the genito-anal region. After primary infection the virus is present in a latent state in neurons in sensory ganglia. Reactivation and production of new viral particles can cause asymptomatic viral shedding or new lesions. Establishment of latency, maintenance and reactivation involve silencing of genes, continuous suppression of gene activities and finally gene activation and synthesis of viral DNA. The purpose of the present work was to study the genetic stability of the virus during these events. Methods HSV-2 was collected from 5 patients with true primary and recurrent infections, and the genes encoding glycoproteins B,G,E and I were sequenced. Results No nucleotide substitution was observed in any patient, indicating genetic stability. However, since the total number of nucleotides in these genes is only a small part of the total genome, we cannot rule out variation in other regions. Conclusions Although infections of cell cultures and animal models are useful for studies of herpes simplex virus, it is important to know how the virus behaves in the natural host. We observed that several glycoprotein gene sequences are stable from primary to recurrent infection. However, the virus isolates from the different patients were genetically different. PMID:24502528

  3. Recurrent recurrent gallstone ileus.

    Hussain, Z; Ahmed, M S; Alexander, D J; Miller, G V; Chintapatla, S


    We describe the second reported case of three consecutive episodes of gallstone ileus and ask the question whether recurrent gallstone ileus justifies definitive surgery to the fistula itself or can be safely managed by repeated enterotomies.

  4. Arthroscopic repair for combined Bankart and superior labral anterior posterior lesions: a comparative study between primary and recurrent anterior dislocation in the shoulder.

    Kim, Doo-Sup; Yi, Chang-Ho; Yoon, Yeu-Seung


    The purpose of this study was to compare clinical outcomes between a primary dislocation group (group P) and a recurrent dislocation group (group R) with combined lesion of Bankart and type II SLAP lesions (type V SLAP lesion) and to evaluate incidence of type V SLAP lesion. In addition, the authors evaluated clinical outcomes of these patients by dividing two groups according to the sequence for Bankart and SLAP lesion suture. From May 2000 to May 2005, 310 patients who gave informed consent, underwent the diagnostic arthroscopy and magnetic resonance arthrography (MRA). One hundred and ten patients met the following criteria: (1) post-traumatic primary or recurrent anterior shoulder instability, (2) a normal contralateral shoulder, (3) a type V SLAP lesion, and (4) minimum follow-up of two years. Group P included 42 patients, and group R, 68 patients. Among all patients, 58 patients who had Bankart lesions sutured first were included in group B, and 52 who had their SLAP lesions sutured beforehand, group S. Visual analogue scale, range of motion, Rowe and Constant score were used to compare results between group P and group R, also group B and group S. The incidence rates of type V SLAP lesion were 42.8% in group P and 32.0% in group R. The overall treatment results in our study were good. Even if the difference between the two groups was statistically insignificant, group P showed greater recovery of range of motion than group R in external rotation. No significant difference was found between the two different operative methods according to suture sequence. The incidence rates of type V SLAP lesion were 42.8% in the primary dislocation group and 32.0% in the recurrent dislocation group. The overall treatment results in our study were good. Although there was no statistical significance in surgical time between the two groups, when both SLAP and Bankart lesions are present, the Bankart lesion must be sutured first to reduce surgical time.

  5. Effects of various cone-beam computed tomography settings on the detection of recurrent caries under restorations in extracted primary teeth

    Kamburoglu, Kivanc; Sonmez, Gul; Kurt, Hakan; Berktas, Zeynep Serap [Dept. of Dentomaxillofacial Radiology, Faculty of Dentistry, Ankara University, Ankara (Turkmenistan); Ozen, Dogukan [Dept. of Biostatistics, Faculty of Veterinary Medicine, Ankara University, Ankara (Turkmenistan)


    The aim of this study was to assess the ex vivo diagnostic ability of 9 different cone-beam computed tomography (CBCT) settings in the detection of recurrent caries under amalgam restorations in primary teeth. Fifty-two primary teeth were used. Twenty-six teeth had dentine caries and 26 teeth did not have dentine caries. Black class II cavities were prepared and restored with amalgam. In the 26 carious teeth, recurrent caries were left under restorations. The other 26 intact teeth that did not have caries served as controls. Teeth were imaged using a 100×90-mm field of view and a 0.2-mm voxel size with 9 different CBCT settings. Four observers assessed the images using a 5-point scale. Kappa values were calculated to assess observer agreement. CBCT settings were compared with the gold standard using a receiver operating characteristic analysis. The area under the curve (AUC) values for each setting were compared using the chi-square test, with a significance level of α=.05. Intraobserver kappa values ranged from 0.366 to 0.664 for observer 1, from 0.311 to 0.447 for observer 2, from 0.597 to 1.000 for observer 3, and from 0.869 to 1 for observer 4. Furthermore, interobserver kappa values among the observers ranged from 0.133 to 0.814 for the first reading and from 0.197 to 0.805 for the second reading. The highest AUC values were found for setting 5 (0.5916) and setting 3 (0.5886), and were not found to be statistically significant (P>.05). Variations in tube voltage and tube current did not affect the detection of recurrent caries under amalgam restorations in primary teeth.

  6. Laparoscopic Totally Extraperitoneal Groin Hernia Repair Using a Self-Gripping Mesh: Clinical Results of 235 Primary and Recurrent Groin Hernias.

    Ozmen, John; Choi, Vincent; Hepburn, Kirsten; Hawkins, Will; Loi, Ken


    Compared with open surgery, laparoscopic groin hernia repair has been shown to significantly reduce postoperative pain. However, chronic pain remains a problem with the laparoscopic approach, affecting approximately 10% of patients. The purpose of this study was to evaluate clinical outcomes following the use of Parietex ProGrip™ (Covidien, Dublin, Ireland) self-gripping mesh during laparoscopic totally extraperitoneal groin hernia repair. Data were collected prospectively from 145 male and 15 female patients with 235 inguinal hernias. All patients underwent repair by the laparoscopic totally extraperitoneal approach using Parietex ProGrip mesh. During follow-up ranging from 5 to 24 months, complications, pain score, patient satisfaction, and recurrence were analyzed. All patients were discharged on the day of surgery or the next morning. There were no immediate complications or returns to the operating room. Delayed postoperative complications included minor bruising to the genital region (3 cases), hematoma/seroma (1 case), and wound infection (1 case). The mean follow-up was 15 months, at which time there were no reports of hernia recurrence and 99% of patients were satisfied with their hernia repair. One patient (0.63%) reported severe pain (numeric rating scale score of >7), and 4 patients (2.5%) reported intermittent mild pain on exertion. The results of this study suggest that the use of a self-gripping mesh during the laparoscopic totally extraperitoneal approach is a promising and effective technique for repairing both primary and recurrent inguinal hernias.

  7. Glioma stem cells are more aggressive in recurrent tumors with malignant progression than in the primary tumor, and both can be maintained long-term in vitro

    Diao Yi


    Full Text Available Abstract Background Despite the advances made during decades of research, the mechanisms by which glioma is initiated and established remain elusive. The discovery of glioma stem cells (GSCs may help to elucidate the processes of gliomagenesis with respect to their phenotype, differentiation and tumorigenic capacity during initiation and progression. Research on GSCs is still in its infancy, so no definitive conclusions about their role can yet be drawn. To understand the biology of GSCs fully, it is highly desirable to establish permanent and biologically stable GSC lines. Methods In the current study, GSCs were isolated from surgical specimens of primary and recurrent glioma in a patient whose malignancy had progressed during the previous six months. The GSCs were cryopreserved and resuscitated periodically during long-term maintenance to establish glioma stem/progenitor cell (GSPC lines, which were characterized by immunofluorescence, flow cytometry and transmission electronic microscopy. The primary and recurrent GSPC lines were also compared in terms of in vivo tumorigenicity and invasiveness. Molecular genetic differences between the two lines were identified by array-based comparative genomic hybridization and further validated by real-time PCR. Results Two GSPC lines, SU-1 (primary and SU-2 (recurrent, were maintained in vitro for more than 44 months and 38 months respectively. Generally, the potentials for proliferation, self-renewal and multi-differentiation remained relatively stable even after a prolonged series of alternating episodes of cryopreservation and resuscitation. Intracranial transplantation of SU-1 cells produced relatively less invasive tumor mass in athymic nude mice, while SU-2 cells led to much more diffuse and aggressive lesions strikingly recapitulated their original tumors. Neither SU-1 nor SU-2 cells reached the terminal differentiation stage under conditions that would induce terminal differentiation in neural

  8. Central nervous system recurrence of systemic lymphoma in the era of stem cell transplantation--an International Primary Central Nervous System Lymphoma Study Group project.

    Bromberg, Jacoline E; Doorduijn, Jeanette K; Illerhaus, Gerald; Jahnke, Kristoph; Korfel, Agniezka; Fischer, Lars; Fritsch, Kristina; Kuittinen, Outti; Issa, Samar; van Montfort, Cees; van den Bent, Martin J


    Autologous stem cell transplantation has greatly improved the prognosis of systemic recurrent non-Hodgkin's lymphoma. However, no prospective data are available concerning the feasibility and efficacy of this strategy for systemic lymphoma relapsing in the central nervous system. We, therefore, we performed an international multicenter retrospective study of patients with a central nervous system recurrence of systemic lymphoma to assess the outcome of these patients in the era of stem cell transplantation. We collected clinical and treatment data on patients with a first central nervous system recurrence of systemic lymphoma treated between 2000 and 2010 in one of five centers in four countries. Patient- and treatment-related factors were analyzed and compared descriptively. Primary outcome measures were overall survival and percentage of patients transplanted. We identified 92 patients, with a median age of 59 years and a median Eastern Cooperative Oncology Group/World Health Organization performance status of 2, of whom 76% had diffuse large B-cell histology. The majority (79%) of these patients were treated with systemic chemotherapy with or without intravenous rituximab. Twenty-seven patients (29%) were transplanted; age and insufficient response to induction chemotherapy were the main reasons for not being transplanted in the remaining 65 patients. The median overall survival was 7 months (95% confidence interval 2.6-11.4), being 8 months (95% confidence interval 3.8-5.2) for patients ≤ 65 years old. The 1-year survival rate was 34.8%; of the 27 transplanted patients 62% survived more than 1 year. The Memorial Sloan Kettering Prognostic Index for primary central nervous system lymphoma was prognostic for both undergoing transplantation and survival. In conclusion, despite the availability of autologous stem cell transplantation for patients with central nervous system progression or relapse of systemic lymphoma, prognosis is still poor. Long-term survival

  9. Correlation of standardized uptake value and apparent diffusion coefficient in integrated whole-body PET/MRI of primary and recurrent cervical cancer.

    Grueneisen, Johannes; Beiderwellen, Karsten; Heusch, Philipp; Buderath, Paul; Aktas, Bahriye; Gratz, Marcel; Forsting, Michael; Lauenstein, Thomas; Ruhlmann, Verena; Umutlu, Lale


    To evaluate a potential correlation of the maximum standard uptake value (SUVmax) and the minimum apparent diffusion coefficient (ADCmin) in primary and recurrent cervical cancer based on integrated PET/MRI examinations. 19 consecutive patients (mean age 51.6 years; range 30-72 years) with histopathologically confirmed primary cervical cancer (n = 9) or suspected tumor recurrence (n = 10) were prospectively enrolled for an integrated PET/MRI examination. Two radiologists performed a consensus reading in random order, using a dedicated post-processing software. Polygonal regions of interest (ROI) covering the entire tumor lesions were drawn into PET/MR images to assess SUVmax and into ADC parameter maps to determine ADCmin values. Pearson's correlation coefficients were calculated to assess a potential correlation between the mean values of ADCmin and SUVmax. In 15 out of 19 patients cervical cancer lesions (n = 12) or lymph node metastases (n = 42) were detected. Mean SUVmax (12.5 ± 6.5) and ADCmin (644.5 ± 179.7 × 10(-5) mm2/s) values for all assessed tumor lesions showed a significant but weak inverse correlation (R = -0.342, p correlation between SUVmax and ADCmin (R = -0.692, p correlation. These initial results of this emerging hybrid imaging technique demonstrate the high diagnostic potential of simultaneous PET/MR imaging for the assessment of functional biomarkers, revealing a significant and strong correlation of tumor metabolism and higher cellularity in cervical cancer lesions.

  10. Possibilities of positron emission tomography in the diagnosis of primary and recurrent ovarian cancer: a review of literature

    L. A. Ashrafyan


    Full Text Available Positron emission tomography (PET is a current radionuclide imaging technique that can supplement a diagnostic process with information on physiological and metabolic disorders in the foci of injury and specify the characteristics of a tumor process. The paper analyzes publications on the use of PET with 18F-fluorodeoxyglucose in different clinical situations in the presence of ovarian cancer for both the identification of early-stage disease, the differential diagnosis of ovarian masses and the timely detection of recurrences, follow-up during and after combination treatment. The authors’ opinions that the technique is restricted, which yields false-positive and false-negative results, are given.

  11. Allergy to house dust mites in primary health care subjects with chronic or recurrent inflammatory states of respiratory system.

    Paszkowski, Jacek; Łopatyński, Jerzy


    Chronic and recurrent respiratory tract disorders are a frequent problem in general practice. The purpose of the study was to investigate the role of hypersensitivity to house dust mites in respiratory tract diseases in general practice patients. We tried to assess the influence of determined risk factors exposure on development of respiratory tract allergy. Patients from family practitioners surgeries with chronic or recurrent respiratory tract symptoms who had no diagnosis of allergy were recruited to the study (n = 89). All patients responded to a questionnaire focused on history of symptoms, atopic conditions in family and exposure to determined environmental factors like dwelling conditions, obstetrician history, diet in the first year of life. All patients underwent skin prick test with common inhalant allergens. Families of the patients were asked to participate in the study. Families who agreed to take part also responded to the questionnaire and underwent skin tests. In patients and their families blood samples were taken to determine total IgE and specific IgE antibodies to mites allergens. Dust samples were collected by vacuuming of patients' bedroom carpets and mattresses to determine house dust mites allergens concentration. Data on 30 complete patients family sets of their brotherhood, mother and father were collected. Total and specific serum IgE antibodies were determined by disc enzyme-immunoassay (Analco). Mites allergens concentration in dust was measured by simple Acarex strip test (Nexter). The results of the assays (positive skin tests and/or elevated levels of specific IgE) showed allergy to house dust mites in 24 of 89 study patients from general practitioners surgeries (27%). The prevalence of chronic rhinitis, recurrent bronchitis, chronic or recurrent cough, wheezing, dyspnoea was higher in allergic than in nonallergic subjects. Patients with the diagnosis of allergy to house dust mites had usually worse dwelling conditions. Especially

  12. Ionotropic glutamate receptors & CNS disorders.

    Bowie, Derek


    Disorders of the central nervous system (CNS) are complex disease states that represent a major challenge for modern medicine. Although aetilogy is often unknown, it is established that multiple factors such as defects in genetics and/or epigenetics, the environment as well as imbalance in neurotransmitter receptor systems are all at play in determining an individual's susceptibility to disease. Gene therapy is currently not available and therefore, most conditions are treated with pharmacological agents that modify neurotransmitter receptor signaling. Here, I provide a review of ionotropic glutamate receptors (iGluRs) and the roles they fulfill in numerous CNS disorders. Specifically, I argue that our understanding of iGluRs has reached a critical turning point to permit, for the first time, a comprehensive re-evaluation of their role in the cause of disease. I illustrate this by highlighting how defects in AMPA receptor (AMPAR) trafficking are important to fragile X mental retardation and ectopic expression of kainate receptor (KAR) synapses contributes to the pathology of temporal lobe epilepsy. Finally, I discuss how parallel advances in studies of other neurotransmitter systems may allow pharmacologists to work towards a cure for many CNS disorders rather than developing drugs to treat their symptoms.

  13. Lower rates of symptom recurrence and surgical revision after primary compared with secondary endoscopic third ventriculostomy for obstructive hydrocephalus secondary to aqueductal stenosis in adults.

    Sankey, Eric W; Goodwin, C Rory; Jusué-Torres, Ignacio; Elder, Benjamin D; Hoffberger, Jamie; Lu, Jennifer; Blitz, Ari M; Rigamonti, Daniele


    OBJECT Endoscopic third ventriculostomy (ETV) is the treatment of choice for obstructive hydrocephalus; however, the success of ETV in patients who have previously undergone shunt placement remains unclear. The present study analyzed 103 adult patients with aqueductal stenosis who underwent ETV for obstructive hydrocephalus and evaluated the effect of previous shunt placement on post-ETV outcomes. METHODS This study was a retrospective review of 151 consecutive patients who were treated between 2007 and 2013 with ETV for hydrocephalus. One hundred three (68.2%) patients with aqueductal stenosis causing obstructive hydrocephalus were included in the analysis. Postoperative ETV patency and aqueductal and cisternal flow were assessed by high-resolution, gradient-echo MRI. Post-ETV Mini-Mental State Examination, Timed Up and Go, and Tinetti scores were compared with preoperative values. Univariate and multivariate analyses were performed comparing the post-ETV outcomes in patients who underwent a primary (no previous shunt) ETV (n = 64) versus secondary (previous shunt) ETV (n = 39). RESULTS The majority of patients showed significant improvement in symptoms after ETV; however, no significant differences were seen in any of the quantitative tests performed during follow-up. Symptom recurrence occurred in 29 (28.2%) patients after ETV, after a median of 3.0 (interquartile range 0.8-8.0) months post-ETV failure. Twenty-seven (26.2%) patients required surgical revision after their initial ETV. Patients who received a secondary ETV had higher rates of symptom recurrence (p = 0.003) and surgical revision (p = 0.003), particularly in regard to additional shunt placement/revision post-ETV (p = 0.005). These differences remained significant after multivariate analysis for both symptom recurrence (p = 0.030) and surgical revision (p = 0.043). CONCLUSIONS Patients with obstructive hydrocephalus due to aqueductal stenosis exhibit symptomatic improvement after ETV, with a

  14. Melanoma patients with unknown primary site or nodal recurrence after initial diagnosis have a favourable survival compared to those with synchronous lymph node metastasis and primary tumour.

    Benjamin Weide

    Full Text Available BACKGROUND: A direct comparison of prognosis between patients with regional lymph node metastases (LNM detected synchronously with the primary melanoma (primary LNM, patients who developed their first LNM subsequently (secondary LNM and those with initial LNM in melanoma with unknown primary site (MUP is missing thus far. PATIENTS AND METHODS: Survival of 498 patients was calculated from the time point of the first macroscopic LNM using Kaplan Meier and multivariate Cox hazard regression analysis. RESULTS: Patients with secondary LNM (HR = 0.67; p = 0.009 and those with initial LNM in MUP (HR = 0.45; p = 0.008 had a better prognosis compared to patients with primary LNM (median survival time 52 and 65 vs. 24 months, respectively. A high number of involved nodes, the presence of in-transit/satellite metastases and male gender had an additional independent unfavourable effect. CONCLUSIONS: Survival of patients with LNM in MUP and with secondary LNM is similar and considerably more favourable compared to those with primary LNM. This difference needs to be considered during patient counselling and for stratification purposes in clinical trials. The assumption of an immune privilege of patients with MUP which is responsible for rejection of the primary melanoma, and results in a favourable prognosis is not supported by our data.

  15. Changes in the ER, PgR, HER2, p53 and Ki-67 biological markers between primary and recurrent breast cancer: discordance rates and prognosis

    Tashima Rumiko


    Full Text Available Abstract Background In breast cancer, ER/PgR, HER2, and Ki-67 are important biological markers for predicting prognosis and making effective treatment decisions. In addition, changes in markers due to relapse are also clinically experienced; however, the frequency and clinical significance are still not fully understood. Thus, changes in markers and their correlations with prognosis were investigated. Patients and Methods Out of the patients with relapse from 1997 to March 2011, there were 97 consecutive patients from whom the lesion was resected and evaluated by immunostaining. The biopsy sites were chest wall, lymph node, ipsilateral breast tumor recurrence, lungs, bones, ovaries and brain. The markers sought were ER, PgR, HER2, p53 and Ki-67. Results The hormone receptor positive rate from the primary tumor to recurrence decreased from 63.9% to 57.7% and from 56.7% to 43.3% for ER and PgR, respectively. Changes in the positive/negative evaluation were seen at the rate of 10.3% and 25.8% for ER and PgR, respectively. The Ki-67 index increased significantly from a mean of 29.1% at primary tumor to 36.3% at relapse. When divided into 2 groups ( Conclusion Estrogen receptor and PgR decreased while Ki-67 increased due to relapse; however, the rate of change was high for PgR and Ki-67. Change in the subtypes was seen in 25%. In addition, PgR at relapse and Ki-67 at primary tumor were significant factors for post-relapse prognosis while PgR becoming negative was a poor prognostic factor. These findings are important for making effective treatment decisions.

  16. Clinical, histological and demographic predictors for recurrence and second primary tumours of head and neck basal cell carcinoma. A 1062 patient-cohort study from a tertiary cancer referral hospital.

    Kyrgidis, Athanassios; Vahtsevanos, Konstantinos; Tzellos, Thrasivoulos George; Xirou, Persa; Kitikidou, Kyriaki; Antoniades, Konstantinos; Zouboulis, Christos C; Triaridis, Stefanos


    Basal cell carcinoma (BCC) accounts for nearly 25% of all cancers in the human body and for almost 75% of skin malignancies; approximately 85% of basal cell carcinomas develop in the head and neck region. Limited demographic, clinical and histological predictors for second primary and/or recurrent BCC have been identified to date. Our objective was to identify predictors of recurrence and second primary tumour development of BCC in the head and neck region. We included 1062 patients with a histologically confirmed diagnosis of BCC. Multivariate and Cox regression analysis were used to access demographic, clinical and histological predictors. Study follow up included 4,302 patient-years, each patient was followed-up for an average 4.0 +/- 1.8 years (range 1-12). Overall recurrence rate was 4%. High-risk histology type was associated with an increased risk for recurrence (odds ratio (OR) = 3.47, 95%CI: 1.07-11.25). We calculated a 4-fold increased risk for recurrence with positive excision margins (OR = 4.31, 95%CI: 1.82-10.22), a 21% increased risk for recurrence (OR = 1.21, 95%CI: 1.06-1.37) and a 25% increased risk for second primary BCC development (OR = 1.25, 95%CI: 1.17-1.34) per year of follow-up. The median time free of second primary tumour was 7 years, while the median time free of recurrence was 12 years. The strongest predictors for recurrence are positive excision margins and high-risk histology type, indicating the need for additional patient care in such cases.

  17. Subsequent neoplasms of the CNS among survivors of childhood cancer: a systematic review.

    Bowers, Daniel C; Nathan, Paul C; Constine, Louis; Woodman, Catherine; Bhatia, Smita; Keller, Karen; Bashore, Lisa


    Childhood cancer survivors are at risk for development of subsequent neoplasms of the CNS. Better understanding of the rates, risk factors, and outcomes of subsequent neoplasms of the CNS among survivors of childhood cancer could lead to more informed screening guidelines. Two investigators independently did a systematic search of Medline and Embase (from January, 1966, through March, 2012) for studies examining subsequent neoplasms of the CNS among survivors of childhood cancer. Articles were selected to answer three questions: what is the risk of CNS tumours after radiation to the cranium for a paediatric cancer, compared with the risk in the general population; what are the outcomes in children with subsequent neoplasms of the CNS who received CNS-directed radiation for a paediatric cancer; and, are outcomes of subsequent neoplasms different from primary neoplasms of the same histology? Our search identified 72 reports, of which 18 were included in this Review. These studies reported that childhood cancer survivors have an 8·1-52·3-times higher incidence of subsequent CNS neoplasms compared with the general population. Nearly all cancer survivors who developed a CNS neoplasm had been exposed to cranial radiation, and some studies showed a correlation between radiation dose and risk of subsequent CNS tumours. 5-year survival ranged from 0-19·5% for subsequent high-grade gliomas and 57·3-100% for meningiomas, which are similar rates to those observed in patients with primary gliomas or meningiomas. The quality of evidence was limited by variation in study design, heterogeneity of details regarding treatment and outcomes, limited follow-up, and small sample sizes. We conclude that survivors of childhood cancer who received cranial radiation therapy have an increased risk for subsequent CNS neoplasms. The current literature is insufficient to comment about the potential harms and benefits of routine screening for subsequent CNS neoplasms.

  18. Objective and subjective image quality of primary and recurrent squamous cell carcinoma on head and neck low-tube-voltage 80-kVp computed tomography

    Scholtz, Jan-Erik; Kaup, Moritz; Kraft, Johannes; Noeske, Eva-Maria; Schulz, Boris; Burck, Iris; Kerl, J.M.; Bauer, Ralf W.; Lehnert, Thomas; Vogl, Thomas J.; Wichmann, Julian L. [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology, Frankfurt (Germany); Scheerer, Friedrich [University Hospital Frankfurt, Department of Cranio-Maxillofacial and Plastic Facial Surgery, Frankfurt (Germany); Wagenblast, Jens [University Hospital Frankfurt, Department of Otolaryngology, Head and Neck Surgery, Frankfurt (Germany)


    To investigate low-tube-voltage 80-kVp computed tomography (CT) of head and neck primary and recurrent squamous cell carcinoma (SCC) regarding objective and subjective image quality. We retrospectively evaluated 65 patients (47 male, 18 female; mean age: 62.1 years) who underwent head and neck dual-energy CT (DECT) due to biopsy-proven primary (n = 50) or recurrent (n = 15) SCC. Eighty peak kilovoltage and standard blended 120-kVp images were compared. Attenuation and noise of malignancy and various soft tissue structures were measured. Tumor signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Subjective image quality was rated by three reviewers using 5-point grading scales regarding overall image quality, lesion delineation, image sharpness, and image noise. Radiation dose was assessed as CT dose index volume (CTDI{sub vol}). Interobserver agreement was calculated using intraclass correlation coefficient (ICC). Mean tumor attenuation (153.8 Hounsfield unit (HU) vs. 97.1 HU), SNR (10.7 vs. 8.3), CNR (8.1 vs. 4.8), and subjective tumor delineation (score, 4.46 vs. 4.13) were significantly increased (all P < 0.001) with 80-kVp acquisition compared to standard blended 120-kVp images. Noise of all measured structures was increased in 80-kVp acquisition (P < 0.001). Overall interobserver agreement was good (ICC, 0.86; 95 % confidence intervals: 0.82-0.89). CTDI{sub vol} was reduced by 48.7 % with 80-kVp acquisition compared to standard DECT (4.85 ± 0.51 vs. 9.94 ± 0.81 mGy cm, P < 0.001). Head and neck CT with low-tube-voltage 80-kVp acquisition provides increased tumor delineation, SNR, and CNR for CT imaging of primary and recurrent SCC compared to standard 120-kVp acquisition with an accompanying significant reduction of radiation exposure. (orig.)

  19. A meta-analysis of surgical morbidity and recurrence after laparoscopic and open repair of primary unilateral inguinal hernia.

    O'Reilly, Elma A


    Laparoscopic inguinal hernia repair (LIHR), using a transabdominal preperitoneal (TAPP) or totally extraperitoneal (TEP) technique, is an alternative to conventional open inguinal hernia repair (OIHR). A consensus on outcomes of LIHR when compared with OIHR for primary, unilateral, inguinal hernia has not been reached.

  20. Acquired von Willebrand disease as a cause of recurrent mucocutaneous bleeding in primary thrombocythemia: Relationship with platelet count

    P.J.J. van Genderen (Perry); J.J. Michiels (Jan); S.C. van der Poel-van de Luytgaarde (Sonja); H.H.D.M. van Vliet (Huib)


    textabstractWe present a 4-year follow-up of a 42-year-old patient with primary thrombocythemia whose clinical course was complicated by two major mucocutaneous bleeding episodes. On both occasions an acquired functional von Willebrand factor deficiency was demonstrated. In contrast to what is repor

  1. Laparoscopic Repair of Primary Inguinal Hernia Performed in Public Hospitals or Low-Volume Centers Have Increased Risk of Reoperation for Recurrence

    Andresen, Kristoffer; Friis-Andersen, Hans; Rosenberg, Jacob


    BACKGROUND: Inguinal hernia repair is traditionally carried out as either open or laparoscopic repair. Laparoscopic repair has been shown to be superior in terms of pain and discomfort, but has a higher risk of reoperation. Quality of inguinal hernia repair is related to factors such as method...... of care. METHODS: This study was based on data from the Danish Hernia Database covering the period from January 1, 1998, to December 31, 2013. Hernia repairs included in this study were laparoscopic repair of primary, inguinal hernias in the elective setting, performed on adult male patients. RESULTS...... reoperation rate compared with public centers: 5.36% versus 8.53%, P ≤ .0001. Type of center and center volume were both independent risk factors for reoperation in a Cox regression model. CONCLUSION: Hospital volume had an effect on the reoperation rate for recurrence after laparoscopic inguinal hernia...

  2. A phase II evaluation of mifepristone in the treatment of recurrent or persistent epithelial ovarian, fallopian or primary peritoneal cancer: a gynecologic oncology group study.

    Rocereto, Thomas F; Brady, William E; Shahin, Mark S; Hoffman, James S; Small, Laurie; Rotmensch, Jacob; Mannel, Robert S


    To evaluate the effectiveness and toxicity of mifepristone in patients with ovarian, peritoneal and fallopian tube cancers. Patients with confirmed epithelial ovarian, peritoneal and fallopian tube cancers which were persistent or recurred in less then 1 year after primary chemotherapy were entered into this study. Patients were given mifepristone 200 mg by mouth daily for a 28 day cycle. The medication was stopped for unacceptable toxicity or tumor progression. Twenty-four patients were entered into the study. Twenty-two patients were evaluable for response. Only one patient had a partial response for a response rate of only 4.5% (90% confidence interval: 0.2%, 19.8%). Mifepristone has not proven to be an effective agent in the treatment of patients with recurrent or persistent ovarian, peritoneal and fallopian tube cancers.

  3. Remote prognosis after primary cesarean delivery: the association of VBACs and recurrent cesarean deliveries with maternal morbidity

    Erez O


    Full Text Available Offer Erez1, Lena Novack2, Vered Kleitman-Meir1, Doron Dukler1, Idit Erez-Weiss3, Francesca Gotsch4, Moshe Mazor11Department of Obstetrics and Gynecology, Soroka University Medical Center, 2Department of Epidemiology, 3Department of Family Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; 4Obstetrics and Gynecology Departement, Policlinico GB Rossi Azienda Ospedaliera Universitaria Integrata Verona, ItalyPurpose: To determine the effects of vaginal birth after cesarean (VBAC versus repeated cesarean sections (RCS after a primary cesarean section (CS, on the rate of intraoperative and postpartum maternal morbidity.Patients and methods: This is a retrospective population-based cohort study. During the study period (1988–2005 there were 200,012 deliveries by 76,985 women at our medical center; 16,365 of them had a primary CS, of which 7429 women delivered a singleton infant after the primary CS, met the inclusion criteria, were included in our study, and were followed for four consecutive deliveries. Patients were divided into three study groups according to the outcome of their consecutive delivery after the primary CS: VBAC (n = 3622, elective CS (n = 1910, or an urgent CS (n = 1897. Survival analysis models were used to investigate the effect of the urgency of CS and the numbers of pregnancy predating the primary CS on peripartum complications.Results: Women who failed a trial of labor had a higher rate of uterine rupture than those who had a VBAC. Patients who delivered by CS had a higher rate of endometritis than those giving birth vaginally. The rate of cesarean hysterectomy and transfer to other departments increased significantly at the fourth consecutive surgery (P = 0.02 and P = 0.003, respectively. VBAC was associated with a 55% reduction in the risk of intrapartum complications in comparison to a planned CS (hazard ratio [HR] 0.45; 95% confidence interval [CI]: 0.22–0.89. A greater

  4. Recurrent varicocele

    Katherine Rotker


    Full Text Available Varicocele recurrence is one of the most common complications associated with varicocele repair. A systematic review was performed to evaluate varicocele recurrence rates, anatomic causes of recurrence, and methods of management of recurrent varicoceles. The PubMed database was evaluated using keywords "recurrent" and "varicocele" as well as MESH criteria "recurrent" and "varicocele." Articles were not included that were not in English, represented single case reports, focused solely on subclinical varicocele, or focused solely on a pediatric population (age <18. Rates of recurrence vary with the technique of varicocele repair from 0% to 35%. Anatomy of recurrence can be defined by venography. Management of varicocele recurrence can be surgical or via embolization.

  5. {sup 18}F-FDOPA PET/MRI fusion in patients with primary/recurrent gliomas: Initial experience

    Ledezma, Carlos J. [Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail:; Chen, Wei [Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail:; Sai, Victor [School of Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail:; Freitas, Bonnie [Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail:; Cloughesy, Tim [Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail:; Czernin, Johannes [Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail:; Pope, Whitney [Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail:


    Background and purpose: {sup 18}F-FDOPA PET demonstrates higher sensitivity and specificity for gliomas than traditional [{sup 18}F] FDG PET imaging. However, PET provides limited anatomic localization. The purpose of this study was to determine whether {sup 18}F-FDOPA PET/MRI fusion can provide precise anatomic localization of abnormal tracer uptake and how this activity corresponds to MR signal abnormality. Methods: Two groups of patients were analyzed. Group I consisted of 21 patients who underwent {sup 18}F-FDOPA PET and MRI followed by craniotomy for tumor resection. Group II consisted of 70 patients with a pathological diagnosis of glioma that had {sup 18}F-FDOPA PET and MRI but lacked additional pathologic follow-up. Fused {sup 18}F-FDOPA PET and MRI images were analyzed for concordance and correlated with histopathologic data. Results: Fusion technology facilitated precise anatomical localization of {sup 18}F-FDOPA activity. In group I, all 21 cases showed pathology-confirmed tumor. Of these, {sup 18}F-FDOPA scans were positive in 9/10 (90%) previously unresected tumors, and 11/11 (100%) of recurrent tumors. Of the 70 patients in group II, concordance between MRI and {sup 18}F-FDOPA was found in 49/54 (90.1%) of patients with sufficient follow-up; in the remaining 16 patients concordance could not be determined due to lack of follow-up. {sup 18}F-FDOPA labeling was comparable in both high- and low-grade gliomas and identified both enhancing and non-enhancing tumor equally well. In some cases, {sup 18}F-FDOPA activity preceded tumor detection on MRI. Conclusion: {sup 18}F-FDOPA PET/MRI fusion provides precise anatomic localization of tracer uptake and labels enhancing and non-enhancing tumor well. In a small minority of cases, {sup 18}F-FDOPA activity may identify tumor not visible on MRI.

  6. Observations at the CNS-PNS Border of Ventral Roots Connected to a Neuroma.

    Remahl, Sten; Angeria, Maria; Remahl, Ingela Nilsson; Carlstedt, Thomas; Risling, Mårten


    Previous studies have shown that numerous sprouts originating from a neuroma, after nerve injury in neonatal animals, can invade spinal nerve roots. However, no study with a focus on how such sprouts behave when they reach the border between the central and peripheral nervous system (CNS-PNS border) has been published. In this study we have in detail examined the CNS-PNS border of ventral roots in kittens with light and electron microscopy after early postnatal sciatic nerve resection. A transient ingrowth of substance P positive axons was observed into the CNS, but no spouts remained 6 weeks after the injury. Using serial sections and electron microscopy it was possible to identify small bundles of unmyelinated axons that penetrated from the root fascicles for a short distance into the CNS. These axons ended blindly, sometimes with a growth cone-like terminal swelling filled with vesicles. The axon bundles were accompanied by p75 positive cells in both the root fascicles and the pia mater, but not in the CNS. It may thus be suggested that neurotrophin presenting p75 positive cells could facilitate axonal growth into the pia mater and that the lack of such cells in the CNS compartment might contribute to the failure of growth into the CNS. A maldevelopment of myelin sheaths at the CNS-PNS border of motor axons was observed and it seems possible that this could have consequences for the propagation of action potential across this region after neonatal nerve injury. Thus, in this first detailed study on the behavior of recurrent sprouts at the CNS-PNS border.

  7. Primary Gleason Grade 4 Impact on Biochemical Recurrence After Permanent Interstitial Brachytherapy in Japanese Patients With Low- or Intermediate-Risk Prostate Cancer

    Uesugi, Tatsuya [Department of Urology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan); Saika, Takashi, E-mail: [Department of Urology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan); Edamura, Kohei; Nose, Hiroyuki; Kobuke, Makoto; Ebara, Shin; Abarzua, Fernand [Department of Urology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan); Katayama, Norihisa [Department of Radiology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan); Yanai, Hiroyuki [Department of Pathology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan); Nasu, Yasutomo; Kumon, Hiromi [Department of Urology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan)


    Purpose: To reveal a predictive factor for biochemical recurrence (BCR) after permanent prostate brachytherapy (PPB) using iodine-125 seed implantation in patients with localized prostate cancer classified as low or intermediate risk based on National Comprehensive Cancer Network (NCCN) guidelines. Methods and Materials: From January 2004 to December 2009, 414 consecutive Japanese patients with clinically localized prostate cancer classified as low or intermediate risk based on the NCCN guidelines were treated with PPB. The clinical factors including pathological data reviewed by a central pathologist and follow-up data were prospectively collected. Kaplan-Meier and Cox regression analyses were used to assess the factors associated with BCR. Results: Median follow-up was 36.5 months. The 2-, 3-, 4-, and 5-year BCR-free rates using the Phoenix definition were 98.3%, 96.0%, 91.6%, and 87.0%, respectively. On univariate analysis, the Gleason score, especially primary Gleason grade 4 in biopsy specimens, was a strong predicting factor (p < 0.0001), while age, initial prostate-specific antigen (PSA) level, T stage, and minimal dose delivered to 90% of the prostate volume (D90) were insignificant. Multivariate analysis indicated that a primary Gleason grade 4 was the most powerful prognostic factor associated with BCR (hazard ratio = 6.576, 95% confidence interval, 2.597-16.468, p < 0.0001). Conclusions: A primary Gleason grade 4 carried a worse BCR prognosis than the primary grade 3 in patients treated with PPB. Therefore, the indication for PPB in patients with a Gleason sum of 4 + 3 deserves careful and thoughtful consideration.

  8. C.N.S. tumors in eastern Saudi Arabia.

    Ibrahim, A W


    In Saudi Arabia, there were no attempts previously to describe a population based frequency or incidence, particularly so the age adjusted incidence of various CNS tumors. This paper presents the primary CNS tumors from a population based tumor registry over two years period, from January 1987 till December 1988. There was a total of 85 cases representing 5.4% of the total captured cases (1,568 cases of malignant tumors at all sites). The population of the Eastern Province is estimated to be 1.37 million, the Saudis forming 80% of the total population. Out of the 85 cases captured over two years, there were 64 cases diagnosed in indigenous Saudi population forming 75%. The remaining occurred in non-Saudi residents. The male/female ratio in Saudis was 1:1.1 with a slight predominance of the female, while the reverse is true in the non-Saudis (2:1). The total captured cases per annum is 43, making the incidence of primary CNS neoplasms in the Eastern Province of Saudi Arabia 3.1/100,000 of all the population and 2.9/100,000 in Saudi nationals. Comparing this incidence to the international figure, it was clear that it is far less than the incidence reported from North America and Europe, particularly in the Caucasian population, but similar to incidences reported in the Chinese, black Americans, Romanians and Yugoslavians, but certainly less than the Ashkenazi or Safari Jews, and slightly higher than the incidence reported in Japan and Southeast Asia. Malignant brain tumors of various types dominated the primary CNS neoplasms reported over these two years forming 69% of the cases and 52% of the primary brain tumors.

  9. Linfoma cerebral primario: revisión bibliográfica y experiencia en el Hospital de Navarra en los últimos 5 años (2000-2004 Primary CNS Lymphoma: bibliographical review and experience at the Hospital of Navarre in the last 5 years (2000-2004

    I. Zazpe


    Full Text Available El linfoma cerebral primario (PCNSL, "Primary CNS Lymphoma" es un linfoma no Hodgkin agresivo que se origina en el sistema nervioso central sin evidencia de linfoma en otra localización en el momento del diagnóstico. Los linfomas cerebrales primarios son menos conocidos y caracterizados que sus homólogos los linfomas sistémicos, por tratarse de una entidad poco frecuente hasta hace unas décadas. Sin embargo, el gran ascenso de incidencia que está experimentando esta patología en las últimas tres décadas y que aún no ha sido explicado, hace necesario la existencia de más estudios para conocer mejor la etiopatogenia de esta entidad. Gracias a los nuevos regímenes de tratamiento, el pronóstico de esta patología ha mejorado significativamente en los últimos años. Sin embargo, el tratamiento del linfoma cerebral primario continúa planteando numerosas controversias en la actualidad, debido a su elevada neurotoxicidad en los pacientes mayores de 60 años, grupo de pacientes frecuentemente afectado por esta patología. Para resolver éstas y otras cuestiones se precisa ahondar en el estudio del linfoma cerebral primario y la realización de potentes ensayos clínicos.Primary cerebral lymphoma (Primary CNS Lymphoma, PCNSL is an aggressive non-Hodgkin lymphoma that originates in the central nervous system without evidence of lymphoma in any other localization at the time of diagnosis. Primary cerebral lymphomas are less well-known and are characterized than their homologues the systemic lymphomas, as they are an entity whose frequency was scarce until a few decades ago. However, the great rise in incidence that this pathology has undergone over the last three decades, and which is still unexplained, makes more studies necessary to better understand the etiopathology of this entity. Thanks to the new systems of treatment, the prognosis of this pathology has improved significantly in recent years. Nonetheless, treatment of primary cerebral

  10. Recurrence Patterns and Second Primary Lung Cancers After Stereotactic Body Radiation Therapy for Early-Stage Non-Small-Cell Lung Cancer: Implications for Surveillance.

    Spratt, Daniel E; Wu, Abraham J; Adeseye, Victoria; Din, Shaun U; Shaikh, Fauzia; Woo, Kaitlin M; Zhang, Zhigang; Foster, Amanda; Rosenzweig, Kenneth E; Gewanter, Richard; Huang, James; Rimner, Andreas


    Patients treated with stereotactic body radiation therapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) are subject to locoregional and distant recurrence, as well as the formation of second primary lung cancers (SPLCs). The optimal surveillance regimen for patients treated with SBRT for early-stage NSCLC remains unclear; we therefore investigated the posttreatment recurrence patterns and development of SPLCs. Three hundred sixty-six patients with pathologically proven inoperable early-stage NSCLC treated with SBRT between 2006 and 2013 were assessed. Patients underwent a computed tomographic (CT) scan of the chest every 3 months during years 1 and 2, every 6 months during years 3 and 4, and annually thereafter. Competing risk analysis was used for all time-to-event analyses. With a median follow-up of 23 months, the 2-year cumulative incidence of local, nodal, and distant treatment failures were 12.2%, 16.1%, and 15.5%, respectively. In patients with disease progression after SBRT (n = 108), 84% (n = 91) of cases occurred within the first 2 years. Five percent (n = 19) of patients experienced SPLCs. The median time to development of an SPLC was 16.5 months (range, 6.5-71.1 months), with 33% (n = 6) of these patients experiencing SPLCs after 2 years. None of the never smokers, but 4% of former tobacco smokers and 15% of current tobacco smokers, experienced an SPLC (P = .005). Close monitoring with routine CT scans within the first 2 years after SBRT is effective in detecting early disease progression. In contrast, the risk for the development of an SPLC remains elevated beyond 2 years, particularly in former and current smokers. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Recurrent Intracerebral Hemorrhage

    Schmidt, Linnea Boegeskov; Goertz, Sanne; Wohlfahrt, Jan;


    the use of any of the investigated medicines with antithrombotic effect (ATT, SSRI's, NSAID's) and recurrent ICH. CONCLUSIONS: The substantial short-and long-term recurrence risks warrant aggressive management of hypertension following a primary ICH, particularly in patients treated surgically...... treatment and renal insufficiency were associated with increased recurrence risks (RR 1.64, 95% CI 1.39-1.93 and RR 1.72, 95% CI 1.34-2.17, respectively), whereas anti-hypertensive treatment was associated with a reduced risk (RR 0.82, 95% CI 0.74-0.91). We observed non-significant associations between...


    S. L. Piskunova


    Full Text Available The article presents the results of examination of 1849 children, entering children's infectioushospitalofVladivostokwith the clinical picture of croup of viral etiology. The clinical features of primary and recurrent croup are described. Frequency of recurrent croup inVladivostokis 8%. Children with a recurrent croup had the burdened premorbid background, and also persistent herpetic infections (cytomegalic infection in 42,9% cases, cytomegalic infection in combination with the herpes simplex virus -1. Frequency of croups substantially rose in the period of epidemic of influenza.

  13. Metallothionein expression and roles in the CNS

    Penkowa, Milena


    -I+II) are regulated and expressed coordinately and are currently the best characterized MT isoforms. This review will focus on the expression and roles of MT-I+II in the CNS. MT-I+II are implicated in diverse physiological and pathophysiological functions, such as metal ion metabolism, regulation of the CNS...

  14. Microglial responses around intrinsic CNS neurons are correlated with axonal regeneration

    Tohyama Koujiro; Campbell Gregor; Lieberman A Robert; Siddiqui Samir; Wong Bernadette ZY; Shokouhi Bahman N; Anderson Patrick N


    Abstract Background Microglia/macrophages and lymphocytes (T-cells) accumulate around motor and primary sensory neurons that are regenerating axons but there is little or no microglial activation or T-cell accumulation around axotomised intrinsic CNS neurons, which do not normally regenerate axons. We aimed to establish whether there was an inflammatory response around the perikarya of CNS neurons that were induced to regenerate axons through a peripheral nerve graft. Results When neurons of ...

  15. Predictors of Recurrent AKI.

    Siew, Edward D; Parr, Sharidan K; Abdel-Kader, Khaled; Eden, Svetlana K; Peterson, Josh F; Bansal, Nisha; Hung, Adriana M; Fly, James; Speroff, Ted; Ikizler, T Alp; Matheny, Michael E


    Recurrent AKI is common among patients after hospitalized AKI and is associated with progressive CKD. In this study, we identified clinical risk factors for recurrent AKI present during index AKI hospitalizations that occurred between 2003 and 2010 using a regional Veterans Administration database in the United States. AKI was defined as a 0.3 mg/dl or 50% increase from a baseline creatinine measure. The primary outcome was hospitalization with recurrent AKI within 12 months of discharge from the index hospitalization. Time to recurrent AKI was examined using Cox regression analysis, and sensitivity analyses were performed using a competing risk approach. Among 11,683 qualifying AKI hospitalizations, 2954 patients (25%) were hospitalized with recurrent AKI within 12 months of discharge. Median time to recurrent AKI within 12 months was 64 (interquartile range 19-167) days. In addition to known demographic and comorbid risk factors for AKI, patients with longer AKI duration and those whose discharge diagnosis at index AKI hospitalization included congestive heart failure (primary diagnosis), decompensated advanced liver disease, cancer with or without chemotherapy, acute coronary syndrome, or volume depletion, were at highest risk for being hospitalized with recurrent AKI. Risk factors identified were similar when a competing risk model for death was applied. In conclusion, several inpatient conditions associated with AKI may increase the risk for recurrent AKI. These findings should facilitate risk stratification, guide appropriate patient referral after AKI, and help generate potential risk reduction strategies. Efforts to identify modifiable factors to prevent recurrent AKI in these patients are warranted. Copyright © 2016 by the American Society of Nephrology.

  16. Patient, Physician, and Nurse Factors Associated With Entry Onto Clinical Trials and Finishing Treatment in Patients With Primary or Recurrent Uterine, Endometrial, or Cervical Cancer


    Recurrent Cervical Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Uterine Corpus Sarcoma; Stage I Uterine Corpus Cancer; Stage I Uterine Sarcoma; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Uterine Corpus Cancer; Stage II Uterine Sarcoma; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Uterine Sarcoma; Stage IV Uterine Corpus Cancer; Stage IV Uterine Sarcoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  17. Risk of recurrent acute lower urinary tract infections and prescription pattern of antibiotics in women with and without diabetes in primary care

    Gorter, Kees J.; Hak, Eelko; Zuithoff, Nicolaas P. A.; Hoepelman, Andy I. M.; Rutten, Guy E. H. M.


    Aim. To investigate diabetes characteristics associated with the risk of recurrent lower UTIs and the antibiotic prescription pattern. Methods. In an exploratory retrospective study involving 7063 women aged >= 30 years, we studied the incidence of recurrent UTI (relapses and reinfection) in women w

  18. Cost-effectiveness of nurse-led self-help for recurrent depression in the primary care setting : Design of a pragmatic randomised controlled trial

    Biesheuvel-Leliefeld, Karolien E M; Kersten, Sandra M A; van der Horst, Henriette E; van Schaik, Anneke; Bockting, Claudi L H; Bosmans, Judith E; Smit, Filip; van Marwijk, Harm W J


    BACKGROUND: Major Depressive Disorder is a leading cause of disability, tends to run a recurrent course and is associated with substantial economic costs due to increased healthcare utilization and productivity losses. Interventions aimed at the prevention of recurrences may reduce patients' sufferi

  19. INS/CNS/GNSS integrated navigation technology

    Quan, Wei; Gong, Xiaolin; Fang, Jiancheng


    This book not only introduces the principles of INS, CNS and GNSS, the related filters and semi-physical simulation, but also systematically discusses the key technologies needed for integrated navigations of INS/GNSS, INS/CNS, and INS/CNS/GNSS, respectively. INS/CNS/GNSS integrated navigation technology has established itself as an effective tool for precise positioning navigation, which can make full use of the complementary characteristics of different navigation sub-systems and greatly improve the accuracy and reliability of the integrated navigation system. The book offers a valuable reference guide for graduate students, engineers and researchers in the fields of navigation and its control. Dr. Wei Quan, Dr. Jianli Li, Dr. Xiaolin Gong and Dr. Jiancheng Fang are all researchers at the Beijing University of Aeronautics and Astronautics.

  20. HIV-1 target cells in the CNS

    Joseph, Sarah B.; Arrildt, Kathryn T.; Sturdevant, Christa B.; Swanstrom, Ronald


    HIV-1 replication in the central nervous system (CNS) is typically limited by the availability of target cells. HIV-1 variants that are transmitted and dominate the early stages of infection almost exclusively use the CCR5 coreceptor and are well adapted to entering, and thus infecting, cells expressing high CD4 densities similar to those found on CD4+ T cells. While the “immune privileged” CNS is largely devoid of CD4+ T cells, macrophage and microglia are abundant throughout ...

  1. CNS toxoplasmosis in an immunocompetent individual


    Toxoplasmosis is a serious and life-threatening disease in humans with a high prevalence in immunocompromised persons. The disease has a wide spectrum, depending on the immune status of the person. A CNS manifestation of toxoplasmosis in an immunocompetent person is very rare and often undetected. Our case of CNS toxoplasmosis in an immunocompetent person emphasizes the radiological diagnosis, which was further confirmed by advanced microbiology technique.

  2. CNS toxoplasmosis in an immunocompetent individual

    Rajoo Ramachandran, MBBS, MD


    Full Text Available Toxoplasmosis is a serious and life-threatening disease in humans with a high prevalence in immunocompromised persons. The disease has a wide spectrum, depending on the immune status of the person. A CNS manifestation of toxoplasmosis in an immunocompetent person is very rare and often undetected. Our case of CNS toxoplasmosis in an immunocompetent person emphasizes the radiological diagnosis, which was further confirmed by advanced microbiology technique.

  3. Knowledge-Based, Central Nervous System (CNS) Lead Selection and Lead Optimization for CNS Drug Discovery.

    Ghose, Arup K; Herbertz, Torsten; Hudkins, Robert L; Dorsey, Bruce D; Mallamo, John P


    The central nervous system (CNS) is the major area that is affected by aging. Alzheimer's disease (AD), Parkinson's disease (PD), brain cancer, and stroke are the CNS diseases that will cost trillions of dollars for their treatment. Achievement of appropriate blood-brain barrier (BBB) penetration is often considered a significant hurdle in the CNS drug discovery process. On the other hand, BBB penetration may be a liability for many of the non-CNS drug targets, and a clear understanding of the physicochemical and structural differences between CNS and non-CNS drugs may assist both research areas. Because of the numerous and challenging issues in CNS drug discovery and the low success rates, pharmaceutical companies are beginning to deprioritize their drug discovery efforts in the CNS arena. Prompted by these challenges and to aid in the design of high-quality, efficacious CNS compounds, we analyzed the physicochemical property and the chemical structural profiles of 317 CNS and 626 non-CNS oral drugs. The conclusions derived provide an ideal property profile for lead selection and the property modification strategy during the lead optimization process. A list of substructural units that may be useful for CNS drug design was also provided here. A classification tree was also developed to differentiate between CNS drugs and non-CNS oral drugs. The combined analysis provided the following guidelines for designing high-quality CNS drugs: (i) topological molecular polar surface area of <76 Å(2) (25-60 Å(2)), (ii) at least one (one or two, including one aliphatic amine) nitrogen, (iii) fewer than seven (two to four) linear chains outside of rings, (iv) fewer than three (zero or one) polar hydrogen atoms, (v) volume of 740-970 Å(3), (vi) solvent accessible surface area of 460-580 Å(2), and (vii) positive QikProp parameter CNS. The ranges within parentheses may be used during lead optimization. One violation to this proposed profile may be acceptable. The

  4. Recurrent mutations of the exportin 1 gene (XPO1) and their impact on selective inhibitor of nuclear export compounds sensitivity in primary mediastinal B-cell lymphoma.

    Jardin, Fabrice; Pujals, Anais; Pelletier, Laura; Bohers, Elodie; Camus, Vincent; Mareschal, Sylvain; Dubois, Sydney; Sola, Brigitte; Ochmann, Marlène; Lemonnier, François; Viailly, Pierre-Julien; Bertrand, Philippe; Maingonnat, Catherine; Traverse-Glehen, Alexandra; Gaulard, Philippe; Damotte, Diane; Delarue, Richard; Haioun, Corinne; Argueta, Christian; Landesman, Yosef; Salles, Gilles; Jais, Jean-Philippe; Figeac, Martin; Copie-Bergman, Christiane; Molina, Thierry Jo; Picquenot, Jean Michel; Cornic, Marie; Fest, Thierry; Milpied, Noel; Lemasle, Emilie; Stamatoullas, Aspasia; Moeller, Peter; Dyer, Martin J S; Sundstrom, Christer; Bastard, Christian; Tilly, Hervé; Leroy, Karen


    Primary mediastinal B-cell lymphoma (PMBL) is an entity of B-cell lymphoma distinct from the other molecular subtypes of diffuse large B-cell lymphoma (DLBCL). We investigated the prevalence, specificity, and clinical relevance of mutations of XPO1, which encodes a member of the karyopherin-β nuclear transporters, in a large cohort of PMBL. PMBL cases defined histologically or by gene expression profiling (GEP) were sequenced and the XPO1 mutational status was correlated to genetic and clinical characteristics. The XPO1 mutational status was also assessed in DLBCL, Hodgkin lymphoma (HL) and mediastinal gray-zone lymphoma (MGZL).The biological impact of the mutation on Selective Inhibitor of Nuclear Export (SINE) compounds (KPT-185/330) sensitivity was investigated in vitro. XPO1 mutations were present in 28/117 (24%) PMBL cases and in 5/19 (26%) HL cases but absent/rare in MGZL (0/20) or DLBCL (3/197). A higher prevalence (50%) of the recurrent codon 571 variant (p.E571K) was observed in GEP-defined PMBL and was associated with shorter PFS. Age, International Prognostic Index and bulky mass were similar in XPO1 mutant and wild-type cases. KPT-185 induced a dose-dependent decrease in cell proliferation and increased cell-death in PMBL cell lines harboring wild type or XPO1 E571K mutant alleles. Experiments in transfected U2OS cells further confirmed that the XPO1 E571K mutation does not have a drastic impact on KPT-330 binding. To conclude the XPO1 E571K mutation represents a genetic hallmark of the PMBL subtype and serves as a new relevant PMBL biomarker. SINE compounds appear active for both mutated and wild-type protein. Am. J. Hematol. 91:923-930, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Carboplatin-pemetrexed in treatment of patients with recurrent/metastatic cancers of the head and neck; superior outcomes in oropharyngeal primaries.

    Binu eMalhotra


    Full Text Available Background – Platinum based therapy in combination with 5-fluorouracil with cetuximab has shown the best survival in pts with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN. The purpose of this study is to evaluate the efficacy and tolerability of carboplatin, pemetrexed and to assess differential outcomes in patients with oropharyngeal primary and HPV related disease.Patients and Methods –The charts of consecutive patients with R/M SCCHN were reviewed. All patients receiving at least 1 cycle of the 2-drug regimen (pemetrexed 500 mg/m2, carboplatin area under the curve of 5 intravenously, were included for assessment of response, safety, toxicity and survival.Results - A total of 86 patients received this regimen between January 2008 and December 2012, of which, 63 were included in this analysis. Forty one percent (26 of the patients had cancers of the oropharynx, and of those, 50% had HPV positive disease, 32% (20 had cancers of the larynx and 24% (15 of the oral cavity. Median number of cycles administered was 4 (range 1-14 cycles with 50% of the patients receiving 4 or more cycles. Half the patients achieved stable disease as their best response, 8% (5 attained a partial response, 24% progressed on therapy and the remaining patients (12 could not have their response assessed.On the basis of Kaplan Meier analysis, median progression free survival (PFS was 5.1 months (95% CI 3.2, 6.2 and median overall survival (OS was 9.4 months (95% CI 4.3, 13.1. Among pts with oropharyngeal primary (n=26, median PFS was 6.4 months (95% CI 2.8, 7.9 and median OS was 16.6 months (95% CI 9.6, 19.5. Among HPV+ pts (n=13, median PFS was 7.0 months (95% CI 4.8, ne and median OS was 17.1 months (95% CI 11.2, 21.7. Conclusion: Combination carboplatin-pemetrexed is an effective and well tolerated treatment, associated with a median PFS of 5.1 months and a clinical benefit in at least 57% of the patients treated.

  6. Environmental cues from CNS, PNS, and ENS cells regulate CNS progenitor differentiation

    Brännvall, Karin; Corell, Mikael; Forsberg-Nilsson, Karin;


    Cellular origin and environmental cues regulate stem cell fate determination. Neuroepithelial stem cells form the central nervous system (CNS), whereas neural crest stem cells generate the peripheral (PNS) and enteric nervous system (ENS). CNS neural stem/progenitor cell (NSPC) fate determination...

  7. Recurrent vulvovaginitis.

    Powell, Anna M; Nyirjesy, Paul


    Vulvovaginitis (VV) is one of the most commonly encountered problems by a gynecologist. Many women frequently self-treat with over-the-counter medications, and may present to their health-care provider after a treatment failure. Vulvovaginal candidiasis, bacterial vaginosis, and trichomoniasis may occur as discreet or recurrent episodes, and have been associated with significant treatment cost and morbidity. We present an update on diagnostic capabilities and treatment modalities that address recurrent and refractory episodes of VV.

  8. An invertebrate model for CNS drug discovery

    Al-Qadi, Sonia; Schiøtt, Morten; Hansen, Steen Honoré


    BACKGROUND: ABC efflux transporters at the blood brain barrier (BBB), namely the P-glycoprotein (P-gp), restrain the development of central nervous system (CNS) drugs. Consequently, early screening of CNS drug candidates is pivotal to identify those affected by efflux activity. Therefore, simple,...... barriers. CONCLUSION: Findings suggest a conserved mechanism of brain efflux activity between insects and vertebrates, confirming that this model holds promise for inexpensive and high-throughput screening relative to in vivo models, for CNS drug discovery......., high-throughput and predictive screening models are required. The grasshopper (locust) has been developed as an invertebrate in situ model for BBB permeability assessment, as it has shown similarities to vertebrate models. METHODS: Transcriptome profiling of ABC efflux transporters in the locust brain......BACKGROUND: ABC efflux transporters at the blood brain barrier (BBB), namely the P-glycoprotein (P-gp), restrain the development of central nervous system (CNS) drugs. Consequently, early screening of CNS drug candidates is pivotal to identify those affected by efflux activity. Therefore, simple...


    Kool, Marcel; Sturm, Dominik; Northcott, Paul A.; Jones, David T. W.; Korshunov, Andrey; Lichter, Peter; Pfister, Stefan


    BACKGROUND: According to the current WHO classification of CNS tumors, childhood CNS primitive neuro-ectodermal tumors (CNS-PNETs; WHO °IV) are poorly differentiated embryonal tumors with early onset and aggressive clinical behavior. Histological diagnosis can be complicated by morphological heterogeneity and divergent differentiation. Recent studies suggest the existence of molecular subgroups of CNS-PNETs sharing biological characteristics with other childhood CNS tumors. Here, we aimed at ...

  10. Requirements for an Integrated UAS CNS Architecture

    Templin, Fred; Jain, Raj; Sheffield, Greg; Taboso, Pedro; Ponchak, Denise


    The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) is investigating revolutionary and advanced universal, reliable, always available, cyber secure and affordable Communication, Navigation, Surveillance (CNS) options for all altitudes of UAS operations. In Spring 2015, NASA issued a Call for Proposals under NASA Research Announcements (NRA) NNH15ZEA001N, Amendment 7 Subtopic 2.4. Boeing was selected to conduct a study with the objective to determine the most promising candidate technologies for Unmanned Air Systems (UAS) air-to-air and air-to-ground data exchange and analyze their suitability in a post-NextGen NAS environment. The overall objectives are to develop UAS CNS requirements and then develop architectures that satisfy the requirements for UAS in both controlled and uncontrolled air space. This contract is funded under NASAs Aeronautics Research Mission Directorates (ARMD) Aviation Operations and Safety Program (AOSP) Safe Autonomous Systems Operations (SASO) project and proposes technologies for the Unmanned Air Systems Traffic Management (UTM) service. Communications, Navigation and Surveillance (CNS) requirements must be developed in order to establish a CNS architecture supporting Unmanned Air Systems integration in the National Air Space (UAS in the NAS). These requirements must address cybersecurity, future communications, satellite-based navigation APNT, and scalable surveillance and situational awareness. CNS integration, consolidation and miniaturization requirements are also important to support the explosive growth in small UAS deployment. Air Traffic Management (ATM) must also be accommodated to support critical Command and Control (C2) for Air Traffic Controllers (ATC). This document therefore presents UAS CNS requirements that will guide the architecture.

  11. Pigmented villonodular synovitis of the ankle-radiation therapy as a primary treatment to reduce recurrence: a case report with 8-year follow-up.

    Schnirring-Judge, Molly; Lin, Bonnie


    Pigmented villonodular synovitis (PVNS) is a rare, benign, idiopathic proliferative disorder of the synovium that results in villous and or nodular formations that have been reported to manifest within joints, tendon sheaths, and bursae. The overall incidence includes 2% to 10% that occur within the foot and ankle joints. PVNS has a high rate of recurrence and up to a 45% recurrence rate has been reported despite surgical intervention. Although traditional treatment for PVNS includes synovectomy with arthroplasty of the affected joint, radiation therapy is now suggested as an adjunctive therapy that is believed to reduce recurrence of the disease. We present a case of PVNS where the patient was treated in 2 stages: surgical resection of the tumor with arthroplasty of the ankle joint followed by radiation therapy. A retrospective review of the chart, radiographs, and MRIs was conducted for a 36-year-old, African American female who had been treated and followed for 8 years. Pathologic examination of the tumor confirmed the diagnosis of PVNS. No evidence of recurrent PVNS was identified in the long-term postoperative MRI examination. The fact that ancillary imaging examinations failed to reveal evidence of recurrence and that the patient expresses a very high patient satisfaction supports the potential benefit of adjunctive radiation therapy for this condition. Copyright © 2011 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Recurrent fevers.

    Isaacs, David; Kesson, Alison; Lester-Smith, David; Chaitow, Jeffrey


    An 11-year-old girl had four episodes of fever in a year, lasting 7-10 days and associated with headache and neck stiffness. She had a long history of recurrent urticaria, usually preceding the fevers. There was also a history of vague pains in her knees and in the small joints of her hands. Her serum C-reactive protein was moderately raised at 41 g/L (normal <8). Her rheumatologist felt the association of recurrent fevers that lasted 7 or more days with headaches, arthralgia and recurrent urticaria suggested one of the periodic fever syndromes. Genetic testing confirmed she had a gene mutation consistent with one of tumour necrosis factor receptor-associated periodic syndrome.

  13. Delusional Disorder Arising From a CNS Neoplasm.

    Stupinski, John; Kim, Jihye; Francois, Dimitry


    Erotomania arising from a central nervous system (CNS) neoplasm has not been previously described. Here, we present the first known case, to our knowledge, of erotomania with associated persecutory delusions arising following diagnosis and treatment of a left frontal lobe brain tumor.

  14. Immune regulation and CNS autoimmune disease

    Antel, J P; Owens, T


    The central nervous system is a demonstrated target of both clinical and experimental immune mediated disorders. Immune regulatory mechanisms operative at the levels of the systemic immune system, the blood brain barrier, and within the CNS parenchyma are important determinants of the intensity a...

  15. Editorial Commentary: Leveraging the Literature: What Can a Half-Century's Worth of Studies Tell Us About Recurrent Instability Following Primary Shoulder Dislocation?

    Cote, Mark P


    A benefit of systematic review (SR) research methods is that well-performed reviews allow authors and readers to identify weaknesses and variability in the orthopaedic literature. An SR on the topic of recurrence rates after conservative treatment of first-time shoulder dislocation provides an excellent example. The example reviews studies covering more than one-half century of time and employing varying methodological designs; the results include estimates of recurrence of shoulder dislocation ranging widely (from 4% to 94.5%). These methods and results raise concerns over the comparability of the studies included in the review. Fortunately, the authors are careful in their use of these data. Although there is little doubt that the review includes a heterogeneous group of articles (and patients), there is value in knowing that much of the variability in the reported rate of recurrence could be related to variations in patient age. Future research, building on more than 50 years of study, would be wise to consider the rate of recurrence among specific age groups. This seems a worthy finding and demonstrates the value of SR methods and the importance of critical analysis of research data. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  16. Impact on survival of early detection of isolated breast recurrences after the primary treatment for breast cancer : a meta-analysis

    Lu, W.L.; Jansen, L.; Post, W.J.; Bonnema, J.; van de Velde, J.C.; de Bock, G.H.

    Purpose The purpose was to establish the impact on survival of early detection of a local recurrence of breast cancer as compared to late detection. Design A meta-analysis was carried out using Cochrane review manager software (RevMan version 4.2). Studies were included if women were treated for

  17. Impact of primary local treatment on the development of distant metastases or death through locoregional recurrence in young breast cancer patients

    Bantema-Joppe, E. J.; van den Heuvel, E. R.; de Munck, L.; de Bock, G. H.; Smit, W. G. J. M.; Timmer, P. R.; Dolsma, W. V.; Jansen, L.; Siesling, S.; Langendijk, J. A.; Maduro, J. H.; Schroder, Carolien; Schroder, Carolien


    In this study, we tested the hypothesis whether breast conserving therapy (BCT) compared with mastectomy is associated with a negative outcome in terms of distant metastases or death (DMD) and investigated the relation between locoregional recurrence (LRR) and DMD in young breast cancer (BC) patient

  18. Linfoma ileal primário como uma causa de intussuscepção ileocecal recorrente Primary ileal lymphoma as a cause of recurrent ileocecal

    Fábio César Miranda Torricelli


    examination was unremarkable except for a palpable mass at the right lower quadrant. Abdominal sonography revealed ileocecal intussusception. Colonoscopy showed a protruding mass from the orifice of ileocecal valve which was reduced, and the patient had full withdrawal of symptoms. Three weeks later, the patient came back to our hospital with recurrent symptoms. Laparotomy was performed and a polypoid mass was noted at the terminal ileum with intussusception into the cecum. A right hemicolectomy was performed. After pathologic examination and tumor staging, a primary Burkitt lymphoma of the distal ileum was diagnosed. Postoperative convalescence was uneventful and the patient was referred to adjuvant chemotherapy.

  19. Pomalidomide shows significant therapeutic activity against CNS lymphoma with a major impact on the tumor microenvironment in murine models.

    Li, Zhimin; Qiu, Yushi; Personett, David; Huang, Peng; Edenfield, Brandy; Katz, Jason; Babusis, Darius; Tang, Yang; Shirely, Michael A; Moghaddam, Mehran F; Copland, John A; Tun, Han W


    Primary CNS lymphoma carries a poor prognosis. Novel therapeutic agents are urgently needed. Pomalidomide (POM) is a novel immunomodulatory drug with anti-lymphoma activity. CNS pharmacokinetic analysis was performed in rats to assess the CNS penetration of POM. Preclinical evaluation of POM was performed in two murine models to assess its therapeutic activity against CNS lymphoma. The impact of POM on the CNS lymphoma immune microenvironment was evaluated by immunohistochemistry and immunofluorescence. In vitro cell culture experiments were carried out to further investigate the impact of POM on the biology of macrophages. POM crosses the blood brain barrier with CNS penetration of ~ 39%. Preclinical evaluations showed that it had significant therapeutic activity against CNS lymphoma with significant reduction in tumor growth rate and prolongation of survival, that it had a major impact on the tumor microenvironment with an increase in macrophages and natural killer cells, and that it decreased M2-polarized tumor-associated macrophages and increased M1-polarized macrophages when macrophages were evaluated based on polarization status. In vitro studies using various macrophage models showed that POM converted the polarization status of IL4-stimulated macrophages from M2 to M1, that M2 to M1 conversion by POM in the polarization status of lymphoma-associated macrophages is dependent on the presence of NK cells, that POM induced M2 to M1 conversion in the polarization of macrophages by inactivating STAT6 signaling and activating STAT1 signaling, and that POM functionally increased the phagocytic activity of macrophages. Based on our findings, POM is a promising therapeutic agent for CNS lymphoma with excellent CNS penetration, significant preclinical therapeutic activity, and a major impact on the tumor microenvironment. It can induce significant biological changes in tumor-associated macrophages, which likely play a major role in its therapeutic activity against CNS

  20. Dual-Energy CT-Based Differentiation of Benign Posttreatment Changes From Primary or Recurrent Malignancy of the Head and Neck: Comparison of Spectral Hounsfield Units at 40 and 70 keV and Iodine Concentration.

    Yamauchi, Hideomi; Buehler, Mark; Goodsitt, Mitchell M; Keshavarzi, Nahid; Srinivasan, Ashok


    The goals of our study were to evaluate dual-energy CT (DECT) differences between benign posttreatment changes and primary or recurrent head and neck malignancies in terms of spectral Hounsfield units for virtual monochromatic series at 40 keV and iodine concentration and compare their utility with that of spectral Hounsfield units at 70 keV. A retrospective review of patients with a history of head and neck malignancy evaluated with DECT of the neck from November 2012 through December 2014 revealed 16 patients with benign posttreatment changes and 24 with malignancies (17 primary tumors and seven recurrent tumors). One reader placed ROIs within benign posttreatment changes or malignant tumors in each patient to generate spectral Hounsfield units at 40 keV, iodine concentration, and spectral Hounsfield units at 70 keV, and the Wilcoxon rank sum test was used to evaluate the differences between the two cohorts. ROC curves were also generated, and AUC and partial AUC were calculated at the three following specificities: 75%, 80%, and 90%. Malignant tissues were significantly different from benign posttreatment changes in spectral Hounsfield units at 40 keV (p concentration (p units at 70 keV (p = 0.0001). The AUCs were 0.949, 0.943, and 0.858 for spectral Hounsfield units at 40 keV, iodine concentration, and spectral Hounsfield units at 70 keV, respectively. Both spectral Hounsfield units at 40 keV and iodine concentration had statistically higher partial AUCs than spectral Hounsfield units at 70 keV at 90% specificity (p = 0.0133 and 0.0063, respectively) but were not significantly different from each other. DECT-derived spectral Hounsfield units at 40 keV and iodine concentration may be superior to spectral Hounsfield units at 70 keV, which is similar to MDCT, in differentiating benign posttreatment changes from primary or recurrent head and neck malignancies.

  1. MAG, myelin and overcoming growth inhibition in the CNS

    McKerracher, Lisa; Rosen, Kenneth M


    While neurons in the central nervous system (CNS) have the capacity to regenerate their axons after injury, they fail to do so, in part because regeneration is limited by growth inhibitory proteins present in CNS myelin...

  2. Considerations for an Integrated UAS CNS Architecture

    Templin, Fred L.; Jain, Raj; Sheffield, Greg; Taboso-Bellesteros, Pedro; Ponchak, Denise


    The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) is investigating revolutionary and advanced universal, reliable, always available, cyber secure and affordable Communication, Navigation, Surveillance (CNS) options for all altitudes of UAS operations. In Spring 2015, NASA issued a Call for Proposals under NASA Research Announcements (NRA) NNH15ZEA001N, Amendment 7 Subtopic 2.4. Boeing was selected to conduct a study with the objective to determine the most promising candidate technologies for Unmanned Air Systems (UAS) air-to-air and air-to-ground data exchange and analyze their suitability in a post-NextGen NAS environment. The overall objectives are to develop UAS CNS requirements and then develop architectures that satisfy the requirements for UAS in both controlled and uncontrolled air space. This contract is funded under NASAs Aeronautics Research Mission Directorates (ARMD) Aviation Operations and Safety Program (AOSP) Safe Autonomous Systems Operations (SASO) project and proposes technologies for the Unmanned Air Systems Traffic Management (UTM) service.There is a need for accommodating large-scale populations of Unmanned Air Systems (UAS) in the national air space. Scale obviously impacts capacity planning for Communication, Navigation, and Surveillance (CNS) technologies. For example, can wireless communications data links provide the necessary capacity for accommodating millions of small UASs (sUAS) nationwide? Does the communications network provide sufficient Internet Protocol (IP) address space to allow air traffic control to securely address both UAS teams as a whole as well as individual UAS within each team? Can navigation and surveillance approaches assure safe route planning and safe separation of vehicles even in crowded skies?Our objective is to identify revolutionary and advanced CNS alternatives supporting UASs operating at all altitudes and in all airspace while accurately navigating in the absence of

  3. Interstitial brachytherapy with 192-IR in treatment of recurrent malignant primary brain tumors. Braquiterapia intersticial con iridio-192 en el tratamiento de recidivas de tumores cerebrales tras cirugia y radioterapia

    Cardenes, R.; Martinez, R.; Victoria, C.; Nuez, L.; Clavo, B.; Sancedo, G. (Clinica Puerta de Hierro. Madrid (Spain))


    Seven patients with recurrent malignant primary brain tumors after surgery and radiation therapy were treated at the Clinica Puerta de Hierro (Madrid) by interstitial brachytherapy with 192-Ir sources. Implantations were performed using computerized tomography and dose prescription were determined following the Paris system rules for interstitial implants. The means dose deliberated was 50 to 65 Gy to the reference isodoses. At the last follow-up all patients except for one are alive and without evidence of progression of the disease. (Author) 35 refs.

  4. Adjuvant therapy with high dose vitamin D following primary treatment of melanoma at high risk of recurrence: a placebo controlled randomised phase II trial (ANZMTG 02.09 Mel-D).

    Saw, Robyn P M; Armstrong, Bruce K; Mason, Rebecca S; Morton, Rachael L; Shannon, Kerwin F; Spillane, Andrew J; Stretch, Jonathan R; Thompson, John F


    Patients with primary cutaneous melanomas that are ulcerated and >2 mm in thickness, >4 mm in thickness and those with nodal micrometastases at diagnosis, have few options for adjuvant treatment. Recent studies have suggested a role for vitamin D to delay melanoma recurrence and improve overall prognosis. This is a pilot placebo-controlled randomised phase II trial to assess the feasibility, safety and toxicity of an oral loading dose of Vitamin D (500,000 IU) followed by an oral dose of 50,000 IU of Vitamin D monthly for 2 years in patients who have been treated for cutaneous melanoma by wide excision of the primary. Patients aged 18-79 years who have completed primary surgical treatment and have Stage IIb, IIc, IIIa (N1a, N2a) or IIIb (N1a, N2a) disease are eligible for randomisation 2:1 to active treatment or placebo. The primary endpoints are sufficiency of dose, adherence to study medication and safety of the drug. The secondary endpoints are participation and progression free survival. The study has been approved by the Ethics Review Committee (RPAH Zone) of the Sydney Local Health District, protocol number X09-0138. Effective, non-toxic adjuvant therapy for high risk primary melanoma is not currently available. Favorable outcomes of this phase II study will form the basis for a multi-centre phase III study to assess whether the addition of oral high-dose vitamin D therapy in patients who have completed primary treatment for melanoma and are at high risk of recurrence will: 1. prolong time to recurrence within 5 years 2. improve overall survival at 5 years and 3. be both safe and tolerable. 62 patients have been randomised since the study commenced in December 2010. Target accrual for the study has been met with 75 patients randomised between December 2010 and August 2014.The Mel-D trial is conducted by the Australia and New Zealand Melanoma Trials Group (ANZMTG 02.09) TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry (ANZCTR) ACTRN

  5. 18F-FDG PET-CT: predicting recurrence in patients following percutaneous cryoablation treatment for stage I primary non-small-cell lung cancer.

    LoGiurato, Brendan; Matthews, Robert; Safaie, Elham; Moore, William; Bilfinger, Thomas; Relan, Nand; Franceschi, Dinko


    The aim of this study was to understand the imaging features of fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET-computed tomography (CT) in postcryoablation lung cancer patients that could help predict recurrence. We identified 28 patients with 30 lesions treated by means of percutaneous cryoablation for stage I non-small-cell lung cancer. Two experienced nuclear radiologists blindly reviewed baseline images and follow-up (18)F-FDG PET-CT scans for a minimum of 24 months, with discrepancy in interpretation resolved by consensus. Nineteen lesions had undergone baseline PET-CT studies, whereas 11 lesions had undergone only baseline CT studies. Follow-up PET-CT studies were analyzed for up to 24 months, whereas the recurrence-free survival analysis was performed for 36 months. The average maximum standardized uptake value (SUV(max)) at baseline (n = 19) was 5.2 ± 3.9 and the average CT area at baseline was 2.2 ± 1.6 cm(2). Only the CT area was significantly different between recurring and nonrecurring lesions at baseline (P = 0.0028). The Kaplan-Meier survival analysis showed that dichotomizing lesions around 2 cm on CT did not result in a statistically significant survival difference (hazard ratio = 1.42, 95% confidence interval: 0.63-2.21). The average SUV(max) at first follow-up was 1.9 ± 1.8 for 27 lesions, whereas the average SUV(max) of recurrent lesions was 2.2 ± 2.2 and that of nonrecurrent lesions was 1.5 ± 0.3 (P = 0.17). Six lesions had SUV(max) more than or equal to 2.5 within 24 months, all of which recurred in the ablation zone. (18)F-FDG PET-CT is a valuable tool for determining treatment response and for distinguishing benign from malignant lesions after cryoablation. The CT area was most predictive of future recurrence at baseline, whereas SUV(max) more than or equal to 2.5 was most predictive of future recurrence at first follow-up.

  6. Diagnosis of deep vein thrombosis, and prevention of deep vein thrombosis recurrence and the post-thrombotic syndrome in the primary care medicine setting anno 2014.

    Michiels, Jan Jacques; Michiels, Janneke Maria; Moossdorff, Wim; Lao, Mildred; Maasland, Hanny; Palareti, Gualtiero


    The requirement for a safe diagnostic strategy of deep vein thrombosis (DVT) should be based on an overall objective post incidence of venous thromboembolism (VTE) of less than 1% during 3 mo follow-up. Compression ultrasonography (CUS) of the leg veins has a negative predictive value (NPV) of 97%-98% indicating the need of repeated CUS testing within one week. A negative ELISA VIDAS safely excludes DVT and VTE with a NPV between 99% and 100% at a low clinical score of zero. The combination of low clinical score and a less sensitive D-dimer test (Simplify) is not sensitive enough to exclude DVT and VTE in routine daily practice. From prospective clinical research studies it may be concluded that complete recanalization within 3 mo and no reflux is associated with a low or no risk of PTS obviating the need of MECS 6 mo after DVT. Partial and complete recanalization after 3 to more than 6 mo is usually complicated by reflux due to valve destruction and symptomatic PTS. Reflux seems to be a main determinant for PTS and DVT recurrence, the latter as a main contributing factor in worsening PTS. This hypothesis is supported by the relation between the persistent residual vein thrombosis (RVT = partial recanalization) and the risk of VTE recurrence in prospective studies. Absence of RVT at 3 mo post-DVT and no reflux is predicted to be associated with no recurrence of DVT (1.2%) during follow-up obviating the need of wearing medical elastic stockings and anticoagulation at 6 mo post-DVT. The presence or absence of RVT but with reflux at 3 to 6 mo post-DVT is associated with both symptomatic PTS and an increased risk of VTE recurrence in about one third in the post-DVT period after regular discontinuation of anticoagulant treatment. To test this hypothesis we designed a prospective DVT and postthrombotic syndrome (PTS) Bridging the Gap Study by addressing at least four unanswered questions in the treatment of DVT and PTS. Which DVT patient has a clear indication for long

  7. VIIP: Central Nervous System (CNS) Modeling

    Vera, Jerry; Mulugeta, Lealem; Nelson, Emily; Raykin, Julia; Feola, Andrew; Gleason, Rudy; Samuels, Brian; Ethier, C. Ross; Myers, Jerry


    Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome. It has been hypothesized that the headward shift of cerebrospinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn may then induce VIIP syndrome through interaction with various biomechanical pathways. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the related IWS works submitted by Nelson et al., Feola et al. and Ethier et al.

  8. microRNAs in CNS disorders

    Kocerha, Jannet; Kauppinen, Sakari; Wahlestedt, Claes


    In recent years, there has been a shift in the conventional paradigms for transcriptional and translational regulation as extensive sequencing efforts have yielded new insights into the landscape of the human genome and transcriptome. Hundreds of non-coding regulatory RNA molecules called microRNAs...... (miRNAs) have been identified in the mammalian central nervous system (CNS) and are reported to mediate pivotal roles in many aspects of neuronal functions. Disruption of miRNA-based post-transcriptional regulation has been implicated in a range of CNS disorders as one miRNA is predicted to impact...... the expression of numerous downstream mRNA targets. The intricate molecular networks mediated by an miRNA form a robust mechanism for rapid and potent responses to cellular events throughout the development of the human brain. Recent studies have identified a molecular and ultimately pathogenic role for a subset...

  9. Interneuron progenitor transplantation to treat CNS dysfunction

    Muhammad O Chohan


    Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

  10. 原发性肝癌术后早期复发密切相关microRNA的筛选及应用%Screening and Validating MicroRNA Associated with Early Recurrence after Radical Surgery in Primary Hepatocellular Carcinoma

    邓治亮; 孙建; 区应亮; 侯宝华; 简志祥; 区金锐


    [Objective] To select effectiveness of microRNAs and correlated with early recurrence after radical surgery in liver cancer by microRNA profiling, which analyzing verified the results by tissue samples on the basis. [Methods] 10 HCC cases with radical surgery were divided into 2 group; early recurrence group and non-early recurrence group, according to postoperative recurrence in primary hepatocellular carcinoma. MicroRNA profiling study were performed to obtain some different and significant microRNAs. According to literature, mir-144 and mir-502-3p were used to detect HCC recurrence by real-time PCR with 82 HCC cases, and target genes were predicted using bioinfbrmatics. [Results] Expression of 7 miRNAs were different and significant in the HCC with early recurrence group. Comparing with non-early recurrrence group, 4 miRNAs were up-regulated in early recurrence group. However, 3 miRNAs were down-regulated. The result of mir-144 and mir-502-3p expression by real-time PCR was uniformity to microarray. Rbl might be a potential target gene of mir-144; SET might be a potential target gene of mir-502-3p. [Conclusions] Mir-144, mir-451, mir-486-5p, mir-602, mir-551b, mir-96, and mir-502-3p were correlated with early recurrence after radical surgery in primary hepatocellular carcinoma with analyzing and screening of microRNA profile by microarray.%[目的]利用micmRNA芯片技术分析比较两组不同复发倾向肝癌患者的miRNA表达谱,并在更大样品的基础上进行实验验证.[方法]收集10例原发性肝癌组织标本根据术后复发情况分2组:早期复发组与非早期复发组,运用microRNA芯片技术筛选出差异表达显著的microRNAs.结合文献报道,选择mir-144、mir-502-3p作为其他82例肝癌组织标本qReal-time PCR验证的检测指标.并利用生物信息学方法预测其靶基因.[结果]本研究共筛选获得7个差异表达的microRNAs.与非早期复发组相比,在早期复发组中有4个表达上调,3

  11. Concurrent Stereotactic Radiosurgery and Bevacizumab in Recurrent Malignant Gliomas: A Prospective Trial

    Cabrera, Alvin R. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Cuneo, Kyle C. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Desjardins, Annick [Department of Surgery, Duke University, Durham, North Carolina (United States); Sampson, John H. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Surgery, Duke University, Durham, North Carolina (United States); McSherry, Frances; Herndon, James E. [Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina (United States); Peters, Katherine B. [Department of Surgery, Duke University, Durham, North Carolina (United States); Allen, Karen [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Hoang, Jenny K. [Department of Radiology, Duke University, Durham, North Carolina (United States); Chang, Zheng; Craciunescu, Oana [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Vredenburgh, James J.; Friedman, Henry S. [Department of Surgery, Duke University, Durham, North Carolina (United States); Kirkpatrick, John P., E-mail: [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Surgery, Duke University, Durham, North Carolina (United States)


    Purpose: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. Methods and Materials: Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter were treated in a single fraction, whereas those 3 to 5 cm in diameter received 5 5-Gy fractions. BVZ was administered immediately before SRS and 2 weeks later. Neurocognitive testing (Mini-Mental Status Exam, Trail Making Test A/B), Functional Assessment of Cancer Therapy-Brain (FACT-Br) quality-of-life assessment, physical exam, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed immediately before SRS and 1 week and 2 months following completion of SRS. The primary endpoint was central nervous system (CNS) toxicity. Secondary endpoints included survival, quality of life, microvascular properties as measured by DCE-MRI, steroid usage, and performance status. Results: One grade 3 (severe headache) and 2 grade 2 CNS toxicities were observed. No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage. Neurocognition, quality of life, and Karnofsky performance status did not change significantly with treatment. DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months. Conclusions: Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospective trial. A randomized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach.

  12. Effects on DHEA levels by estrogen in rat astrocytes and CNS co-cultures via the regulation of CYP7B1-mediated metabolism

    Fex Svenningsen, Åsa; Wicher, Grzegorz; Lundqvist, Johan


    The neurosteroid dehydroepiandrosterone (DHEA) is formed locally in the CNS and has been implicated in several processes essential for CNS function, including control of neuronal survival. An important metabolic pathway for DHEA in the CNS involves the steroid hydroxylase CYP7B1. In previous...... studies, CYP7B1 was identified as a target for estrogen regulation in cells of kidney and liver. In the current study, we examined effects of estrogens on CYP7B1-mediated metabolism of DHEA in primary cultures of rat astrocytes and co-cultures of rat CNS cells. Astrocytes, which interact with neurons...... in several ways, are important for brain neurosteroidogenesis. We found that estradiol significantly suppressed CYP7B1-mediated DHEA hydroxylation in primary mixed CNS cultures from fetal and newborn rats. Also, CYP7B1-mediated DHEA hydroxylation and CYP7B1 mRNA were markedly suppressed by estrogen...

  13. Antiphospholipid and antiprotein syndromes in non-thrombotic, non-autoimmune women with unexplained recurrent primary early foetal loss. The Nîmes Obstetricians and Haematologists Study--NOHA.

    Gris, J C; Quéré, I; Sanmarco, M; Boutiere, B; Mercier, E; Amiral, J; Hubert, A M; Ripart-Neveu, S; Hoffet, M; Tailland, M L; Rousseau, O; Monpeyroux, F; Dauzat, M; Sampol, J; Daures, J P; Berlan, J; Marès, P


    Various antiphospholipid and/or antiprotein antibodies have been suspected to be associated with recurrent early foetal loss in absence of any habitual aetiology. We conducted a hospital-based case control study on women with no antecedent of thromboembolic or autoimmune disease. We studied 3 groups of 518 women: patients with unexplained primary recurrent early foetal loss, patients with explained episodes and mothers with no previous obstetrical accident. Matching the 3 groups was carried out on the basis of age, number or pregnancies and time elapsed since the end of the last pregnancy. Significant biological markers were then prospectively tested. The various antibodies were shown to be dependent on parity and on the presence of previous foetal loss: cut-off values were thus calculated using data obtained from the group of explained accidents, and adjusted for parity. Only anti-phosphatidylethanolamine IgM [odds ratio: 6.0, 95% confidence interval (2.3-15.7), p = 0.0003], anti-beta2-glycoprotein I IgG [4.4, (1.6-11.7), p = 0.0035] anti-annexin V IgG antibodies [3.2 (1.2-8.1), p = 0.015] and lupus anticoagulant [3.0, (1.3-6.8), p = 0.009], were found to be independent retrospective risk factors for unexplained early foetal loss. These four markers were subsequently found to be, during the following pregnancy, associated with a significant risk of foetal loss despite a low-dose aspirin treatment. In non-thrombotic, non-auto-immune women with unexplained primary recurrent early foetal loss, subgroups of patients with positive anti-phosphatidylethanolamine IgM antibodies, or positive anti-beta2-glycoprotein-I IgG antibodies, or positive anti-annexin V IgG antibodies or lupus anticoagulant must be particularised. This should allow therapeutic trials to be carried in well-defined patients.

  14. 原发性肝细胞癌根治术后肿瘤复发的影响因素及预后%Influencing factors and prognosis of tumor recurrence after radical resection of primary hepatocellular carcinoma

    蔡荣耀; 黄志勇; 梁宾勇; 李开艳; 陈孝平


    Objective To investigate the influencing factors and prognosis of early and late recurrence after radical resection of primary hepatocellular carcinoma(HCC).Methods The clinical data of 117 patients who received radical resection of HCC at the Tongji Hospital of Huazhong University of Science and Technology from January 2003 to December 2006 were retrospectively analyzed.Tumor recurrence occurred within 2 years after operation was defined as early recurrence,and tumor recurrence occurred latter than 2 years after operation was defined as late recurrence.Relationship between postoperative tumor recurrence and level of alpha-fetoprotein (AFP),AFP/V,tumor diameter,tumor number,blood vessel invasion,tumor differentiation,hepatic cirrhosis,hepatic function,hepatitis B surface antigen,procedure of hepatic resection and blood transfusion was analyzed.The overall survival and disease-free survival rates were determined by Kaplan-Meier method,and the survival rate was analyzed by Log-rank test.Results Eighty-five(72.6%)patients were found with tumor recurrence,including 59(50.4%)with early tumor recurrence and 26(22.2%)with late tumor recurrence.Levels of AFP,AFP/V,tumor diameter,tumor number,blood vessel invasion,tumor differentiation and blood transfusion were the influencing factors of early recurrence(x2 = 12.78,13.40,5.79,9.98,10.26,9.48,8.32,P < 0.05).Level of AFP and hepatic cirrhosis were the influencing factors of late recurrence(x2 =4.46,7.75,P < 0.05).AFP/V,tumor number and blood vessel invasion were the independent risk factors of early recurrence(RR = 0.170,0.172,0.064,P < 0.05).Hepatic cirrhosis was the independent risk factor of late recurrence(RR = 2.809, P < 0.05).The 1-,3-,5-year overall survival rates and tumor-free survival rates were 82.6%,60.8%,54.9% and 65.0%,38.5%,23.1%.There were significant differences in overall survival and disease-free survival rates among patients with AFP <20 μg/L,AFP/V < 14 μg/(L · cm3)or AFP

  15. SINS/CNS Nonlinear Integrated Navigation Algorithm for Hypersonic Vehicle

    Yong-jun Yu


    Full Text Available Celestial Navigation System (CNS has characteristics of accurate orientation and strong autonomy and has been widely used in Hypersonic Vehicle. Since the CNS location and orientation mainly depend upon the inertial reference that contains errors caused by gyro drifts and other error factors, traditional Strap-down Inertial Navigation System (SINS/CNS positioning algorithm setting the position error between SINS and CNS as measurement is not effective. The model of altitude azimuth, platform error angles, and horizontal position is designed, and the SINS/CNS tightly integrated algorithm is designed, in which CNS altitude azimuth is set as measurement information. GPF (Gaussian particle filter is introduced to solve the problem of nonlinear filtering. The results of simulation show that the precision of SINS/CNS algorithm which reaches 130 m using three stars is improved effectively.

  16. Everolimus, Erlotinib Hydrochloride, and Radiation Therapy in Treating Patients With Recurrent Head and Neck Cancer Previously Treated With Radiation Therapy


    Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Tongue Cancer

  17. Recurrent seizures after lidocaine ingestion.

    Aminiahidashti, Hamed; Laali, Abolghasem; Nosrati, Nazanin; Jahani, Fatemeh


    Lidocaine has a concentration-dependent effect on seizures. Concentrations above 15 μg/mL frequently result in seizures in laboratory animals and human. We report a case of central nervous system (CNS) lidocaine toxicity and recurrent seizure after erroneous ingestion of lidocaine solution. A 4-year-old boy presented to the Emergency Department of Imam Hospital of Sari in December 2013 due to tonic-clonic generalized seizures approximately 30 min ago. 3 h before seizure, his mother gave him 2 spoons (amount 20-25 cc) lidocaine hydrochloride 2% solution instead of pediatric gripe by mistake. Seizure with generalized tonic-clonic occurred 3 times in home. Neurological examination was essentially unremarkable except for the depressed level of consciousness. Personal and medical history was unremarkable. There was no evidence of intracranial ischemic or hemorrhagic lesions in computed tomography scan. There were no further seizures, the condition of the patient remained stable, and he was discharged 2 days after admission. The use of viscous lidocaine may result in cardiovascular and CNS toxicity, particularly in children. Conservative management is the best option for treatment of lidocaine induced seizure.

  18. Recurrent seizures after lidocaine ingestion

    Hamed Aminiahidashti


    Full Text Available Lidocaine has a concentration-dependent effect on seizures. Concentrations above 15 μg/mL frequently result in seizures in laboratory animals and human. We report a case of central nervous system (CNS lidocaine toxicity and recurrent seizure after erroneous ingestion of lidocaine solution. A 4-year-old boy presented to the Emergency Department of Imam Hospital of Sari in December 2013 due to tonic-clonic generalized seizures approximately 30 min ago. 3 h before seizure, his mother gave him 2 spoons (amount 20-25 cc lidocaine hydrochloride 2% solution instead of pediatric gripe by mistake. Seizure with generalized tonic-clonic occurred 3 times in home. Neurological examination was essentially unremarkable except for the depressed level of consciousness. Personal and medical history was unremarkable. There was no evidence of intracranial ischemic or hemorrhagic lesions in computed tomography scan. There were no further seizures, the condition of the patient remained stable, and he was discharged 2 days after admission. The use of viscous lidocaine may result in cardiovascular and CNS toxicity, particularly in children. Conservative management is the best option for treatment of lidocaine induced seizure.

  19. Vulvovaginitis candidiasis recurrence during pregnancy.

    Fardiazar, Z; Ronaci, F; Torab, R; Goldust, M


    Vulvovaginitis is the most common gynecologic condition seen by practitioners rendering primary care to women. Vulvovaginitis Candidiasis (VVC) is the most common type of vaginitis and this study aimed at specifying VVC recurrence during pregnancy. In this prospective study, 150 pregnant women suffering from vaginal excretion, morsus and itching were studied. Initially, the patients were treated using clotrimazole local cream (5 g) for 7 successive days. After initial treatment, the patients were freely visited once a month until delivery considering vaginitis symptoms and VVC recurrence was examined during pregnancy. Mean age of the understudy mothers was 27.26 +/- 3.76. Mean of recurrence number was 0.17 +/- 0.48 during the first trimester. Mean of recurrence number was 0.92 +/- 0.76 during the second trimester. Mean of recurrence number was 2.16 +/- 0.63 during the third trimester. Statistically significant difference was between recurrences during three trimesters of pregnancy (p < 0.001). There is statistically significant difference between mean number of recurrences during three trimesters of pregnancy.

  20. Obstructive hydrocephalus due to CNS toxocariasis.

    Choi, Jae-Hwan; Cho, Jae-Wook; Lee, Jae-Hyeok; Lee, Sang Weon; Kim, Hak-Jin; Choi, Kwang-Dong


    A 46-year-old man developed intermittent headache, diplopia, and visual obscuration for two months. Funduscopic examination showed optic disk swelling in both eyes. Brain MRI exhibited hydrocephalus and leptomeningeal enhancement at the prepontine cistern, left cerebellopontine angle cistern and bilateral cerebral hemisphere, and hemosiderin deposition along the cerebellar folia. CSF analysis revealed an elevated opening pressure with xanthochromic appearance and small amount of red blood cells. Antibody titer against Toxocariasis using ELISA was elevated both in blood and CSF. Obstructive hydrocephalus and hemosiderin deposition in this case may result from the active inflammatory process due to CNS toxocariasis within the subarachnoid space.

  1. Evaluation of CNS activity of Bramhi Ghrita

    Achliya G


    Full Text Available OBJECTIVE: To eavaluate the CNS activity of Bramhi Ghrita, a polyherbal formulation containing Bacopa monneri, Evolvulus alsinoids, Acorus calamus, Saussurea lappa and cow′s ghee. MATERIALS AND METHODS: The effect of Bramhi Ghrita on motor coordination, behavior, sleep, convulsions, locomotion and analgesia was evaluated in mice using standard procedures. RESULTS: The formulation exhibited reduced alertness, spontaneous locomotor activity and reactivity. It also antagonized the behavioral effects of d-amphetamine, potentiated the pentobarbitone-induced sleep and increased the pain threshold. Bramhi Ghrita protected mice from maximum electroshock and pentylene tetrazole-induced convulsions.

  2. Opioids and breast cancer recurrence

    Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P


    BACKGROUND: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. METHODS: Patients with incident, early stage breast cancer who were diagnosed during 1996 through...... 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death......, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months...

  3. Recurrent glomerular disease after kidney transplantation.

    Blosser, Christopher D; Bloom, Roy D


    With improving short-term kidney transplant outcomes, recurrent glomerular disease is being increasingly recognized as an important cause of chronic allograft failure. Further understanding of the risks and pathogenesis of recurrent glomerular disease enable informed transplant decisions, along with the development of preventive and treatment strategies. Multiple observational studies have highlighted differences in rates and outcomes for various recurrent glomerular diseases, although these rates have not markedly improved over the last decade. Emerging evidence supports use of rituximab to treat recurrent primary membranous nephropathy and possibly focal segmental glomerulosclerosis (FSGS), whereas eculizumab is effective in glomerular diseases associated with complement dysregulation [C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS)]. Despite the potential for recurrence in the allograft, transplant remains the optimal therapy for patients with advanced chronic kidney disease (CKD) secondary to primary glomerular disease. Biomarkers and therapeutic options necessitate accurate pretransplant diagnoses with opportunities for improved surveillance and treatment of recurrent glomerular disease posttransplant.

  4. Immune cell trafficking from the brain maintains CNS immune tolerance.

    Mohammad, Mohammad G; Tsai, Vicky W W; Ruitenberg, Marc J; Hassanpour, Masoud; Li, Hui; Hart, Prue H; Breit, Samuel N; Sawchenko, Paul E; Brown, David A


    In the CNS, no pathway dedicated to immune surveillance has been characterized for preventing the anti-CNS immune responses that develop in autoimmune neuroinflammatory disease. Here, we identified a pathway for immune cells to traffic from the brain that is associated with the rostral migratory stream (RMS), which is a forebrain source of newly generated neurons. Evaluation of fluorescently labeled leukocyte migration in mice revealed that DCs travel via the RMS from the CNS to the cervical LNs (CxLNs), where they present antigen to T cells. Pharmacologic interruption of immune cell traffic with the mononuclear cell-sequestering drug fingolimod influenced anti-CNS T cell responses in the CxLNs and modulated experimental autoimmune encephalomyelitis (EAE) severity in a mouse model of multiple sclerosis (MS). Fingolimod treatment also induced EAE in a disease-resistant transgenic mouse strain by altering DC-mediated Treg functions in CxLNs and disrupting CNS immune tolerance. These data describe an immune cell pathway that originates in the CNS and is capable of dampening anti-CNS immune responses in the periphery. Furthermore, these data provide insight into how fingolimod treatment might exacerbate CNS neuroinflammation in some cases and suggest that focal therapeutic interventions, outside the CNS have the potential to selectively modify anti-CNS immunity.

  5. Analysis of recurrence of 760 cases with primary pterygium after surgery%原发性翼状胬肉760例术后复发情况分析

    程海霞; 陈志钧; 刘庆淮; 杨勤


    目的 评价原发性翼状胬肉切除后单纯巩膜暴露法、羊膜移植法及带蒂结膜瓣转移术3种手术方式对其复发率的影响.方法随访门诊2009~2011年749例(760眼)原发性翼状胬肉术后的复发情况,比较不同手术方式治疗原发性翼状胬肉的复发率并对结果做统计学分析.结果单纯巩膜暴露法复发率11.43%(24/210);羊膜移植法复发率5.19%(7/135);带蒂结膜瓣转移术复发率3.37%(14/415).3种不同手术方式术后复发率差异有统计学意义(χ2=16.401,P=0.000 3),其中羊膜移植法与带蒂结膜瓣转移术在治疗翼状胬肉中的疗效相近,复发率较低,两组间复发率差异没有统计学意义(χ2=0.910,P=0.34).结论羊膜移植法与带蒂结膜瓣转移术在治疗翼状胬肉中的疗效相近,较之单纯巩膜暴露法复发率低.%Objective To evaluate the effects of three operation methods which include simpled sclera exposure, amniotic membrane transplantation and conjunctival flap transference on the recurrence of primary pterygium after excision. Methods Seven hundred and forty-nine cases ( 760 eyes ) of primary pterygium after surgery was followed up in the outpatient Opthalmology Department of Jiangsu Provincial Hospital from 2009 to 2011. The recurrence with different operation methods were compared. Results The recurrent rate of simple scleral exposure, amniotic membrane transplantation and conjunctival flap transfer was 11. 43% ( 24/210 ), 5. 19% ( 7/135 ) and 3. 37% ( 14/415 ) respectively. The Chi square test showed significant differences among these three different operation methods( X2 16.401 ,P =0.000 3 ). The amniotic membrane transplantation and the conjunctival flap transference methods had similar curative effect with low recurrence rate and showed no significant difference in the recurrence rate( x2 =0. 910,P = 0.34). Conclusions In treating pterygium, the amniotic membrane transplantation and the conjunctival flap transference methods had

  6. Chemoradiation in patients with unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection.. Analysis of treatment efficacy and failure in patients receiving postoperative or primary chemoradiation

    Habermehl, D.; Lindel, K.; Rieken, S.; Haase, K.; Welzel, T.; Debus, J.; Combs, S.E. [University Hospital of Heidelberg (Germany). Dept. of Radiation Oncology; Goeppert, B.; Schirmacher, P. [Heidelberg Univ. (Germany). Inst. of Pathology; Buechler, M.W. [University Hospital of Heidelberg (Germany). Dept. of Visceral Surgery


    Background: The purpose of this work was to determine efficacy, toxicity, and patterns of recurrence after concurrent chemoradiation (CRT) in patients with extrahepatic bile duct cancer (EHBDC) and hilar cholangiocarcinoma (Klatskin tumours) in case of incomplete resection or unresectable disease. Patients and methods: From 2003-2010, 25 patients with nonmetastasized EHBDC and hilar cholangiocarcinoma were treated with radiotherapy and CRT at our institution in an postoperative setting (10 patients, 9 patients with R1 resections) or in case of unresectable disease (15 patients). Median age was 63 years (range 38-80 years) and there were 20 men and 5 women. Median applied dose was 45 Gy in both patient groups. Results: Patients at high risk (9 times R1 resection, 1 pathologically confirmed lymphangiosis) for tumour recurrence after curative surgery had a median time to disease progression of 8.7 months and an estimated mean overall survival of 23.2 months (6 of 10 patients are still under observation). Patients undergoing combined chemoradiation in case of unresectable primary tumours are still having a poor prognosis with a progression-free survival of 7.1 months and a median overall survival of 12.0 months. The main site of progression was systemic (liver, peritoneum) in both patient groups. Conclusion: Chemoradiation with gemcitabine is safe and can be applied safely in either patients with EHBDC or Klatskin tumours at high risk for tumour recurrence after resection and patients with unresectable tumours. Escalation of systemic and local treatment should be investigated in future clinical trials. (orig.)

  7. 原发性三叉神经痛显微血管减压术后复发相关因素的研究%Related factors of recurrence of primary trigeminal neuralgia after microvascular decompression

    唐四强; 漆松涛; 刘忆; 陈铭; 张喜安; 潘军; 曹永福


    Objective To evaluate the related factors of the recurrence of primary trigeminal neuralgia after microvascular decompression(MVD).Methods 147 patients with initial primary trigeminal neuralgia treated with MVD in our departerment were retrospectively analyzed.The preoperative treatment,clinical presentation,operative findings and postoperative outcomes were recorded.The related factors of recurrence were statically analyzed.Results The mean follow-up time was 39.5 months and the recurrence rate was 11.6% (17/147).The univariate analysis showed that the duration of disease(x2 =8.226,P =0.016),clinical presentation (x2 =4.940,P =0.026),offending artery (x2 =45.759,P =0.000),compression degree(x2 =13.811,P =0.003),decompression degree (x2 =39.910,P =0.000),outer arachnoid(x2 =33.117,P =0.000),arachnoidcompression (x2 =27.245,P =0.000) and arachnoid adhesion(x2 =20.710,P =0.000)were statically related to the recurrence of neuralgia.After the Logistic regression analysis,the outer arachnoid (P =0.033),arachnoid trabecula compression (P =0.008),offending artery (P =0.002) and decompression degree (P =0.004) were the predictors of the recurrence.Conclusions MVD was effective in the treatment of primary trigeminal neuralgia.The arachnoid factors might play an important role in the pathogenesis of trigeminal neuralgia and MVD.%目的 探讨原发性三叉神经痛显微血管减压术后复发的相关因素.方法 回顾性分析我院147例首次经微血管减压术治疗的原发性三叉神经痛患者的临床资料,包括术前治疗方式、临床特征、术中所见、术后第1周时的疗效,并分析随访期内复发的相关因素.结果 147例患者平均随访39.5个月,17例(11.6%)复发;复发的单因素分析显示病程(x2=8.226,P=0.016),临床特征(x2=4.940,P=0.026),责任血管(x2 =45.759,P=0.000),压迫程度(x2=13.811,P=0.003),减压程度(x2=39.910,P=0.000),外层蛛网膜(x2=33.117,P=0.000),蛛网膜卡压(x2=27.245,P=0.000),

  8. Retreatment of recurrent nasopharyngeal carcinoma

    McNeese, M.D.; Fletcher, G.H.


    Thirty patients with recurrent primary nasopharyngeal carcinoma were reirradiated between 1949 and 1976. Twenty eventually demonstrated recurrence at or near the primary site, involving the nasopharynx in 4 and the central nervous system in 16. Long-term palliation was often achieved, and there were no severe complications except for one patient who died of necrosis of the base of the skull. The most frequent problems were hearing loss and trismus; necrosis of the nasopharynx was seen in only 2 patients. With therapy in the range of 18-25 MeV, significant palliation and an occational cure can be achieved without excessive risk. Recurrent disease involving the skull may be controlled for several years using current techniques.

  9. Radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer. Prolonged disease-free interval associated with favorable prognosis

    Nakamura, Akira; Itasaka, Satoshi; Yoshimura, Michio; Matsuo, Yukinori; Mizowaki, Takashi; Hiraoka, Masahiro [Kyoto University, Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto (Japan); Takaori, Kyoichi; Kawaguchi, Yoshiya; Uemoto, Shinji [Kyoto University, Department of Surgery, Graduate School of Medicine, Kyoto (Japan); Shibuya, Keiko [Yamaguchi University Graduate School of Medicine, Department of Therapeutic Radiology, Yamaguchi (Japan)


    To evaluate the treatment outcomes of radiotherapy and prognostic factors for recurrent pancreatic cancer. The study comprised 30 patients who developed a locoregional recurrence of primarily resected pancreatic cancer and received radiotherapy between 2000 and 2013 with a median dose of 54 Gy (range, 39-60 Gy). Concurrent chemotherapy included gemcitabine for 18 patients and S-1 for seven patients. The treatment outcomes and prognostic factors were retrospectively analyzed. The median follow-up after radiotherapy was 14.6 months. The 1-year overall survival, local control, and progression-free survival rates were 69 %, 67 %, and 32 %, respectively. The median overall survival and progression-free survival rates were 15.9 and 6.9 months, respectively. Tumor marker reduction and ≥ 50 % reduction were observed in 18 and two patients, respectively. Of the seven patients who exhibited pain symptoms, four and two patients were partly and completely relieved, respectively. Late grade 3 ileus and gastroduodenal bleeding were observed in one patient each. Among the clinicopathological factors evaluated, only a disease-free interval of greater than 18.9 months exhibited a significant association with improved overall survival (p = 0.017). Radiotherapy for isolated locally recurrent pancreatic cancer resulted in encouraging local control, overall survival, and palliative effects with mild toxicity, particularly in patients with a prolonged disease-free interval. This treatment strategy should be prospectively evaluated. (orig.) [German] Beurteilung strahlentherapeutischer Behandlungsergebnisse und prognostischer Faktoren bei rezidivierendem Pankreaskrebs. In dieser Studie wurden 30 Patienten aufgenommen, bei denen es nach primaer reseziertem Pankreaskrebs zu lokoregionaeren Rezidiven kam und die zwischen 2000 und 2013 strahlentherapeutisch mit einer mittleren Dosis von 54 Gy (Bereich 39-60 Gy) behandelt wurden. Im Rahmen der gleichzeitig durchgefuehrten Chemotherapie wurde

  10. Integrated microfluidics platforms for investigating injury and regeneration of CNS axons.

    Kim, Hyung Joon; Park, Jeong Won; Byun, Jae Hwan; Vahidi, Behrad; Rhee, Seog Woo; Jeon, Noo Li


    We describe the development of experimental platforms to quantify the regeneration of injured central nervous system (CNS) neurons by combining engineering technologies and primary neuronal cultures. Although the regeneration of CNS neurons is an important area of research, there are no currently available methods to screen for drugs. Conventional tissue culture based on Petri dish does not provide controlled microenvironment for the neurons and only provide qualitative information. In this review, we introduced the recent advances to generate in vitro model system that is capable of mimicking the niche of CNS injury and regeneration and also of testing candidate drugs. We reconstructed the microenvironment of the regeneration of CNS neurons after injury to provide as in vivo like model system where the soluble and surface bounded inhibitors for regeneration are presented in physiologically relevant manner using microfluidics and surface patterning methods. The ability to control factors and also to monitor them using live cell imaging allowed us to develop quantitative assays that can be used to compare various drug candidates and also to understand the basic mechanism behind nerve regeneration after injury.


    Raúl Nicolás Carvajal Pérez


    Full Text Available Los estudios de circuitos de distribución comienzan con el cálculo de flujo de potencia por el circuito. Este refleja su estado actual en cuanto a pérdidas y caídas de tensión; básicos para cualquier análisis. Cuando se trabaja con técnicas genéticas, estos cálculos se realizan miles de veces. En este trabajo se sugiere un método de cálculo de flujo de potencia en circuitos de distribución radiales. Se aplica éste cuando solo se conoce la demanda total del circuito utilizando “Ardvinson” para asignar una “demanda de cálculo” a cada nodo. En esencia se realiza una primera iteración utilizando esa demanda y la tensión nominal del circuito en una dirección. La segunda iteración recurre a los valores obtenidos en la primera. Se exponen los cálculos realizados en un circuito real utilizando un sistema de cálculo específico y el Microsoft EXCEL para demostrar la rapidez del método y su nivel de exactitud. The first step in Distribution Circuits studios consist in power flux calculus. It shows the actual situation. of the circuit. When the studio is realized using genetic techniques, this step is repeated thousands times. A method to obtain power flux in distribution circuits is presented. The method is applied when only have the total circuit demand. Here is applied Ardvinson method to obtain “Calculus demand” in each node, realize the first iteration with these demand and nominal tension. Later, repeat the calculus using the values obtained before. An example of real circuit is resolved using specific software and EXCEL to demonstrate the efficiency of the method.

  12. Effects of primary and recurrent sacral chordoma on the motor and nociceptive function of hindlimbs in rats: an orthotopic spine model.

    Sarabia-Estrada, Rachel; Ruiz-Valls, Alejandro; Shah, Sagar R; Ahmed, A Karim; Ordonez, Alvaro A; Rodriguez, Fausto J; Guerrero-Cazares, Hugo; Jimenez-Estrada, Ismael; Velarde, Esteban; Tyler, Betty; Li, Yuxin; Phillips, Neil A; Goodwin, C Rory; Petteys, Rory J; Jain, Sanjay K; Gallia, Gary L; Gokaslan, Ziya L; Quinones-Hinojosa, Alfredo; Sciubba, Daniel M


    OBJECTIVE Chordoma is a slow-growing, locally aggressive cancer that is minimally responsive to conventional chemotherapy and radiotherapy and has high local recurrence rates after resection. Currently, there are no rodent models of spinal chordoma. In the present study, the authors sought to develop and characterize an orthotopic model of human chordoma in an immunocompromised rat. METHODS Thirty-four immunocompromised rats were randomly allocated to 4 study groups; 22 of the 34 rats were engrafted in the lumbar spine with human chordoma. The groups were as follows: UCH1 tumor-engrafted (n = 11), JHC7 tumor-engrafted (n = 11), sham surgery (n = 6), and intact control (n = 6) rats. Neurological impairment of rats due to tumor growth was evaluated using open field and locomotion gait analysis; pain response was evaluated using mechanical or thermal paw stimulation. Cone beam CT (CBCT), MRI, and nanoScan PET/CT were performed to evaluate bony changes due to tumor growth. On Day 550, rats were killed and spines were processed for H & E-based histological examination and immunohistochemistry for brachyury, S100β, and cytokeratin. RESULTS The spine tumors displayed typical chordoma morphology, that is, physaliferous cells filled with vacuolated cytoplasm of mucoid matrix. Brachyury immunoreactivity was confirmed by immunostaining, in which samples from tumor-engrafted rats showed a strong nuclear signal. Sclerotic lesions in the vertebral body of rats in the UCH1 and JHC7 groups were observed on CBCT. Tumor growth was confirmed using contrast-enhanced MRI. In UCH1 rats, large tumors were observed growing from the vertebral body. JHC7 chordoma-engrafted rats showed smaller tumors confined to the bone periphery compared with UCH1 chordoma-engrafted rats. Locomotion analysis showed a disruption in the normal gait pattern, with an increase in the step length and duration of the gait in tumor-engrafted rats. The distance traveled and the speed of rats in the open field test

  13. Robust regeneration of CNS axons through a track depleted of CNS glia.

    Moon, L D; Brecknell, J E; Franklin, R J; Dunnett, S B; Fawcett, J W


    Transected CNS axons do not regenerate spontaneously but may do so if given an appropriate environment through which to grow. Since molecules associated with CNS macroglia are thought to be inhibitory to axon regeneration, we have tested the hypothesis that removing these cell types from an area of brain will leave an environment more permissive for axon regeneration. Adult rats received unilateral knife cuts of the nigrostriatal tract and ethidium bromide (EB) was used to create a lesion devoid of astrocytes, oligodendrocytes, intact myelin sheaths, and NG2 immunoreactive cells from the site of the knife cut to the ipsilateral striatum (a distance of 6 mm). The regenerative response and the EB lesion environment was examined with immunostaining and electron microscopy at different timepoints following surgery. We report that large numbers of dopaminergic nigral axons regenerated for over 4 mm through EB lesions. At 4 days postlesion dopaminergic sprouting was maximal and the axon growth front had reached the striatum, but there was no additional growth into the striatum after 7 days. Regenerating axons did not leave the EB lesion to form terminals in the striatum, there was no recovery of function, and the end of axon growth correlated with increasing glial immunoreactivity around the EB lesion. We conclude that the removal of CNS glia promotes robust axon regeneration but that this becomes limited by the reappearance of nonpermissive CNS glia. These results suggest, first, that control of the glial reaction is likely to be an important feature in brain repair and, second, that reports of axon regeneration must be interpreted with caution since extensive regeneration can occur simply as a result of a major glia-depleting lesion, rather than as the result of some other specific intervention.

  14. Cerebellar metastases of recurrent phyllodes tumor breast; a rare phenomenon reflecting the unpredictable outcome.

    Singh, Jyotsna; Majumdar, Kaushik; Gupta, Rahul; Batra, Vineeta Vijay


    Carcinomas of lung, breast, colon, kidney, and malignant melanomas are the most common malignancies that metastasize to the central nervous system (CNS). Phyllodes tumor is a rare fibroepithelial tumor of the breast, often having unpredictable recurrences, with increasing histological grade and distant metastasis. Malignant forms exist, which may develop distant metastases usually to the lung, pleura, bone, and liver. CNS metastasis of phyllodes tumor is rare and associated with a poor prognosis, with resistance to chemotherapy and radiation. We present a rare case of cerebellar metastasis in recurrent phyllodes tumor breast with subsequent rapid downhill course.

  15. Malign Recurrence of Primary Chest Wall Hemangiopericytoma in the Lung after Four Years: A Case Report and Review of the Literature

    Tulay Akman


    Full Text Available Hemangiopericytoma (HPC may develop in every site where the endothelial tissue exits and primarily develops in the skeletal-muscular system or the skin. Adult cases of HPC generally exhibit a benign course. 20–30% of the cases may show a malign course. The tumors that show more than four mitoses, a focal area of necrosis, and increased cellularity on a magnification ×10 are considered as malign. In our paper, we presented our case who showed a lung metastasis at the end of 4 years and who developed a pathological fracture of the right humerus at the end of approximately 2 years, because hemangiopericytoma is rarely seen in the chest wall as a primary tumor.

  16. A Case of Recurrent Cryptococcal Meningoencephalitis in an Immunocompetent Female

    Negin Niknam


    Full Text Available Cryptococcus neoformans is commonly associated with meningoencephalitis in immunocompromised patients and occasionally in apparently healthy individuals. Duration and regimen of antifungal treatment vary depending on the nature of the host and extent of disease and CNS shunts are placed in persistently elevated intracranial pressures. Recurrence of infection after initial treatment is not uncommon in HIV positive patients, Kaya et al. (2012 and Illnait-zaragozí et al. (2010. We describe a 39-year-old immunocompetent female that presented with neurologic deficits and increased intracranial pressure (ICP due to cryptococcal meningoencephalitis that had a complicated course with drug induced hepatitis and persistently increased ICP that ultimately required shunt placement and presented again with relapse of cryptococcal meningoencephalitis after completion of antifungal treatment. Our case shows that recurrent cryptococcal meningitis can be seen in immunocompetent patients due to prolonged placement of CNS shunt and suggests that shunts should be removed after resolution of meningitis.

  17. Recurrent Candida albicans Ventriculitis Treated with Intraventricular Liposomal Amphotericin B

    Demet Toprak


    Full Text Available Central nervous system (CNS infection with Candida is rare but significant because of its high morbidity and mortality. When present, it is commonly seen among immunocompromised and hospitalized patients. Herein, we describe a case of a four-year-old boy with acute lymphoblastic leukemia (ALL who experienced recurrent Candida albicans meningitis. The patient was treated successfully with intravenous liposomal amphotericin B at first attack, but 25 days after discharge he was readmitted to hospital with symptoms of meningitis. Candida albicans was grown in CFS culture again and cranial magnetic resonance imaging (MRI showed ventriculitis. We administered liposomal amphotericin B both intravenously and intraventricularly and favorable result was achieved without any adverse effects. Intraventricular amphotericin B may be considered for the treatment of recurrent CNS Candida infections in addition to intravenous administration.

  18. A philosophy for CNS radiotracer design.

    Van de Bittner, Genevieve C; Ricq, Emily L; Hooker, Jacob M


    Decades after its discovery, positron emission tomography (PET) remains the premier tool for imaging neurochemistry in living humans. Technological improvements in radiolabeling methods, camera design, and image analysis have kept PET in the forefront. In addition, the use of PET imaging has expanded because researchers have developed new radiotracers that visualize receptors, transporters, enzymes, and other molecular targets within the human brain. However, of the thousands of proteins in the central nervous system (CNS), researchers have successfully imaged fewer than 40 human proteins. To address the critical need for new radiotracers, this Account expounds on the decisions, strategies, and pitfalls of CNS radiotracer development based on our current experience in this area. We discuss the five key components of radiotracer development for human imaging: choosing a biomedical question, selection of a biological target, design of the radiotracer chemical structure, evaluation of candidate radiotracers, and analysis of preclinical imaging. It is particularly important to analyze the market of scientists or companies who might use a new radiotracer and carefully select a relevant biomedical question(s) for that audience. In the selection of a specific biological target, we emphasize how target localization and identity can constrain this process and discuss the optimal target density and affinity ratios needed for binding-based radiotracers. In addition, we discuss various PET test-retest variability requirements for monitoring changes in density, occupancy, or functionality for new radiotracers. In the synthesis of new radiotracer structures, high-throughput, modular syntheses have proved valuable, and these processes provide compounds with sites for late-stage radioisotope installation. As a result, researchers can manage the time constraints associated with the limited half-lives of isotopes. In order to evaluate brain uptake, a number of methods are available

  19. Neurobiology in primary headaches

    Edvinsson, Lars; Uddman, Rolf


    , usually accompanied by nausea, vomiting, photophobia and/or phonophobia. A number of hypothesis have emerged to explain the specific causes of migraine. Current theories suggest that the initiation of a migraine attack involves a primary central nervous system (CNS) event. It has been suggested...

  20. Metallothionein induction in human CNS in vitro: neuroprotection from ionizing radiation.

    Cai, L; Cherian, M G; Iskander, S; Leblanc, M; Hammond, R R


    There have been extensive studies on the regulation of metallothionein (MT) synthesis, and its biological role in liver and kidney. Although there are few reports on brain MT, there is a growing interest in the role of MT in brain. There have been no publications to date on MT synthesis in the human central nervous system (CNS) following exposure to ionizing radiation. In the present study, primary human CNS cultures were used to examine the effect of ionizing radiation on MT mRNA and protein synthesis. In the same cultures, the neuroprotective effects of zinc (Zn) and cadmium (Cd)-induced MT synthesis from high-dose radiation were also examined. Primary, serum-free, human CNS cultures were exposed to 30 or 60 Gy gamma-rays. The total MT protein was then measured by a Cd-heme assay, and mRNA for MT-II and MT-III was detected by reverse transcription polymerase chain reaction (RT-PCR). Cytotoxicity was measured by LDH release and apoptotic cell death by DNA fragmentation analysis. Sublethal neuroglial injury was assessed morphologically using specific astrocytic (glial fibrillary acidic protein--GFAP) and neuronal (microtubule-associated protein 2--MAP2) immunohistochemical markers. The total MT protein content was increased 12h after exposure to 30Gy. The increase in MT content in response to 60Gy was not statistically significant. MT-II mRNA levels increased at 3 and 6h after exposure to 30Gy gamma-rays, with a maximum expression at 12-24 h. MT-III mRNA was not significantly affected. Exposure to 60 Gy, but not 30 Gy, caused a marked increase in LDH release. Cells exposed to 30 Gy or less showed some apoptotic cell death by DNA fragmentation analysis, while exposure to 60 Gy resulted in a DNA smear confirmed by LDH assays. Preinduction of MT by 5 microM Cd or 100 microM Zn resulted in a significant reduction in radiation-induced LDH release. Morphological evaluations revealed that Cd or Zn preincubation led to relative preservation of MAP2 staining and GFAP. Both

  1. Tuning up the developing auditory CNS.

    Sanes, Dan H; Bao, Shaowen


    Although the auditory system has limited information processing resources, the acoustic environment is infinitely variable. To properly encode the natural environment, the developing central auditory system becomes somewhat specialized through experience-dependent adaptive mechanisms that operate during a sensitive time window. Recent studies have demonstrated that cellular and synaptic plasticity occurs throughout the central auditory pathway. Acoustic-rearing experiments can lead to an over-representation of the exposed sound frequency, and this is associated with specific changes in frequency discrimination. These forms of cellular plasticity are manifest in brain regions, such as midbrain and cortex, which interact through feed-forward and feedback pathways. Hearing loss leads to a profound re-weighting of excitatory and inhibitory synaptic gain throughout the auditory CNS, and this is associated with an over-excitability that is observed in vivo. Further behavioral and computational analyses may provide insights into how theses cellular and systems plasticity effects underlie the development of cognitive functions such as speech perception.

  2. Endocannabinoids and synaptic function in the CNS.

    Hashimotodani, Yuki; Ohno-Shosaku, Takako; Kano, Masanobu


    Marijuana affects neural functions through the binding of its active component (Delta(9)-THC) to cannabinoid receptors in the CNS. Recent studies have elucidated that endogenous ligands for cannabinoid receptors, endocannabinoids, serve as retrograde messengers at central synapses. Endocannabinoids are produced on demand in activity-dependent manners and released from postsynaptic neurons. The released endocannabinoids travel backward across the synapse, activate presynaptic CB1 cannabinoid receptors, and modulate presynaptic functions. Retrograde endocannabinoid signaling is crucial for certain forms of short-term and long-term synaptic plasticity at excitatory or inhibitory synapses in many brain regions, and thereby contributes to various aspects of brain function including learning and memory. Molecular identities of the CB1 receptor and enzymes involved in production and degradation of endocannabinoids have been elucidated. Anatomical studies have demonstrated unique distributions of these molecules around synapses, which provide morphological bases for the roles of endocannabinoids as retrograde messengers. CB1-knockout mice exhibit various behavioral abnormalities and multiple defects in synaptic plasticity, supporting the notion that endocannabinoid signaling is involved in various aspects of neural function. In this review article, the authors describe molecular mechanisms of the endocannabinoid-mediated synaptic modulation and its possible physiological significance.

  3. Monitoring the CNS pathology in aspartylglucosaminuria mice.

    Tenhunen, K; Uusitalo, A; Autti, T; Joensuu, R; Kettunen, M; Kauppinen, R A; Ikonen, S; LaMarca, M E; Haltia, M; Ginns, E I; Jalanko, A; Peltonen, L


    Aspartylglucosaminuria (AGU) is a recessively inherited lysosomal storage disorder caused by the deficiency of the aspartylglucosaminidase (AGA) enzyme. The hallmark of AGU is slowly progressing mental retardation but the progression of brain pathology has remained uncharacterized in humans. Here we describe the long-term follow-up of mice carrying a targeted AGU-mutation in both alleles. Immunohistochemistry, histology, electron microscopy, quantitative magnetic resonance imaging (MRI) and behavioral studies were carried out to evaluate the CNS affection of the disease during development. The lysosomal storage vacuoles of the AGA -/- mice were most evident in central brain regions where MRI also revealed signs of brain atrophy similar to that seen in the older human patients. By immunohistochemistry and MRI examinations, a subtle delay of myelination was observed in AGA -/- mice. The life span of the AGA -/- mice was not shortened. Similar to the slow clinical course observed in human patients, the AGA -/- mice have behavioral symptoms that emerge at older age. Thus, the AGU knock-out mice represent an accurate model for AGU, both histopathologically and phenotypically.

  4. Microglial Aging in the Healthy CNS: Phenotypes, Drivers, and Rejuvenation

    Wai T Wong


    Full Text Available Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and age-related macular degeneration, share two characteristics in common: 1 a disease prevalence that increases markedly with advancing age, and 2 neuroinflammatory changes in which microglia, the primary resident immune cell of the CNS, feature prominently. These characteristics have led to the hypothesis that pathogenic mechanisms underlying age-related neurodegenerative disease involve aging changes in microglia. If correct, targeting features of microglial senescence may constitute a feasible therapeutic strategy. This review explores this hypothesis and its implications by considering the current knowledge on how microglia undergo change during aging and how the emergence of these aging phenotypes relate to significant alterations in microglial function. Evidence and theories on cellular mechanisms implicated in driving senescence in microglia are reviewed, as are rejuvenative measures and strategies that aim to reverse or ameliorate the aging microglial phenotype. Understanding and controlling microglial aging may represent an opportunity for elucidating disease mechanisms and for formulating novel therapies.

  5. An evaluation of factors predicting breast recurrence and prognosis after recurrence, on distinguishing intramammary and extramammary recurrence, in breast-conserving surgery

    Nishimura, Reiki; Nagao, Kazuharu; Miyayama, Haruhiko [Kumamoto City Hospital (Japan)] (and others)


    Recurrence of cancer in the breast is an important problem in breast-conserving therapy. We evaluated risk factors for recurrence from the viewpoint of recurrence type and outcome after recurrence. Of 533 cases of breast cancer treated with breast-conserving surgery from April 1989 through July 2000, disease in 66 recurred (12.4%) and were classified as 23 cases of breast recurrence only, 16 cases of both breast recurrence and distant metastasis, and 27 cases of distant metastasis only. The clinical factors examined included age, lymphatic invasion, nodal status, extensive intraductal component (EIC), proliferative activity, and estrogen receptor (ER) status. Of the 39 cases of breast recurrence, 19 had intramammary tumors and 20 had extramammary tumors of the skin, subcutaneous tissue, or muscle, including 8 cases with inflammatory breast recurrence. Multivariate analysis showed that factors correlated with breast recurrence were age, ER status, proliferative activity, and surgical margin. EIC-comedo was related to intramammary recurrence, whereas lymphatic invasion and nodal status were related to extramammary recurrence. Postoperative irradiation was an effective treatment for tumors in young women and tumors with positive margins or a comedo component. Outcome after breast recurrence depended on nodal status at primary operation, and survival rates were worst in patients with inflammatory breast recurrence. In conclusion, age, EIC-comedo status, the surgical margin, and negative ER status were correlated with breast recurrence. Countermeasures against these factors should be investigated. (author)

  6. LINGO-1 and its role in CNS repair.

    Mi, Sha; Sandrock, Alfred; Miller, Robert H


    LINGO-1 is selectively expressed in the CNS on both oligodendrocyte precursor cells (OPCs) and neurons. Its expression is developmentally regulated in the normal CNS, as well as up-regulated in human or rat models of neuropathologies. LINGO-1 functions as a negative regulator of oligodendrocyte differentiation and myelination, neuronal survival and axonal regeneration. Across diverse animal CNS disease models, targeted LINGO-1 inhibition was found to promote neuron and oligodendrocyte survival, axon regeneration, oligodendrocyte differentiation, remyelination and improved functional recovery. The targeted inhibition of LINGO-1 therefore presents a novel therapeutic approach for the treatment of neurological diseases.

  7. 3rd ENRI International Workshop on ATM/CNS


    The Electronic Navigation Research Institute (ENRI) held its third International Workshop on ATM / CNS in 2013 with the theme of "Drafting the future sky". There is worldwide activity taking place in the research and development of modern air traffic management (ATM) and its enabling technologies in Communication, Navigation and Surveillance (CNS). Pioneering work is necessary to contribute to the global harmonization of air traffic management and control. At this workshop, leading experts in  research, industry and academia from around the world met to share their ideas and approaches on ATM/CNS related topics.

  8. A rare case of CNS tuberculosis with pregnancy

    Sanjay Singh


    Full Text Available Whereas pelvic tuberculosis leading to infertility is quite common in female population of developing countries, Central Nervous System (CNS tuberculosis (TB with pregnancy is a rare entity. Most of the information on this subject is based on sporadic case reports only. Most of the earlier reports suggest very high adverse outcome of CNS Tuberculosis in pregnancy. We are presenting a case of CNS Tuberculosis which was diagnosed timely and managed appropriately in our institute with a favourable outcome, thus highlighting the importance of early diagnosis and treatment. [Int J Reprod Contracept Obstet Gynecol 2015; 4(3.000: 911-914

  9. Recurrent Primary Breast Lymphoma in Nipple of the Same Side after Surgery: Report of One Case%原发性乳腺淋巴瘤术后同侧乳头复发一例

    李志峰; 陈建新; 常仁安; 陈钟


    目的 总结原发性乳腺淋巴瘤(primary breast lymphoma,PBL)的临床病理学、免疫组织化学特征、综合治疗及复发情况.方法 对2010年11月入院手术切除的PBL术后同侧乳头复发的1例患者的临床资料进行回顾分析,病理常规切片及免疫组织化学观察.结果 光学显微镜检查低倍镜下肿瘤细胞弥漫性浸润破坏乳头组织,导致乳头结构紊乱,肿块乳管结构紊乱;高倍镜下显示瘤细胞成分多样,以中等大小细胞和大细胞为主,肿瘤细胞弥漫侵犯小血管.免疫组织化学结果显示Ki-67(>90%),CD20(+),bcl-6(+),MUM1(+),CD43(灶+),CD3(-),CD10(-).符合恶性非霍奇金淋巴瘤.结论 PBL是一种少见的结外淋巴瘤,临床表现缺乏特异性,术前很难与乳腺其他良、恶性病变区分,其诊断主要依靠术后病理.目前单纯肿块切除术+放射治疗联合全身化学疗法是治疗PBL临床共识,肿瘤复发可能与Ki-67高度表达存在相关性.%Objective To investigate the clinical pathology, immunohistochemical features, comprehensive treatment, recurrence and prognosis of primary breast lymphoma (PBL). Methods We retrospectively analyzed the clinical data including general information and pathological and immnohistochemical examinations of one patient with recurrent PBL in nipple of the same side after surgery who was admitted into our hospital in November 2010. Results Under low-power optical microscope lens, we found that the tumor cells diffused and infiltrated the nipple tissue which looked quite disorganized. Under high-power lens, we observed various tumor cells, especially the medium-and large-sized tumor cells which infiltrated small vessels. The results of immunohistochemical tests were as follows: Ki-67 (>90%), CD20 (+), bcl-6 ( + ), MUM1 ( + ), CD43 (nidus+), CD3 (-), and CD10 (-). All these indexes indicated malignant non-Hodgkin's lymphoma. Conclusions PBL is a kind of extremely rare extra-nodal lymphoma with low

  10. Convulsant bicuculline modifies CNS muscarinic receptor affinity

    Rodríguez de Lores Arnaiz Georgina


    Full Text Available Abstract Background Previous work from this laboratory has shown that the administration of the convulsant drug 3-mercaptopropionic acid (MP, a GAD inhibitor, modifies not only GABA synthesis but also binding of the antagonist [3H]-quinuclidinyl benzilate ([3H]-QNB to central muscarinic receptors, an effect due to an increase in affinity without modifications in binding site number. The cholinergic system has been implicated in several experimental epilepsy models and the ability of acetylcholine to regulate neuronal excitability in the neocortex is well known. To study the potential relationship between GABAergic and cholinergic systems with seizure activity, we analyzed the muscarinic receptor after inducing seizure by bicuculline (BIC, known to antagonize the GABA-A postsynaptic receptor subtype. Results We analyzed binding of muscarinic antagonist [3H]-QNB to rat CNS membranes after i.p. administration of BIC at subconvulsant (1.0 mg/kg and convulsant (7.5 mg/kg doses. Subconvulsant BIC dose failed to develop seizures but produced binding alteration in the cerebellum and hippocampus with roughly 40% increase and 10% decrease, respectively. After convulsant BIC dose, which invariably led to generalized tonic-clonic seizures, binding increased 36% and 15% to cerebellar and striatal membranes respectively, but decreased 12% to hippocampal membranes. Kd value was accordingly modified: with the subconvulsant dose it decreased 27% in cerebellum whereas it increased 61% in hippocampus; with the convulsant dose, Kd value decreased 33% in cerebellum but increased 85% in hippocampus. No change in receptor number site was found, and Hill number was invariably close to unity. Conclusion Results indicate dissimilar central nervous system area susceptibility of muscarinic receptor to BIC. Ligand binding was modified not only by a convulsant BIC dose but also by a subconvulsant dose, indicating that changes are not attributable to the seizure process

  11. Loss of Coupling Distinguishes GJB1 Mutations Associated with CNS Manifestations of CMT1X from Those Without CNS Manifestations

    Abrams, Charles K.; Goman, Mikhail; Wong, Sarah; Scherer, Steven S.; Kleopa, Kleopas A.; Peinado, Alejandro; Freidin, Mona M.


    CMT1X, an X-linked inherited neuropathy, is caused by mutations in GJB1, which codes for Cx32, a gap junction protein expressed by Schwann cells and oligodendrocytes. Many GJB1 mutations cause central nervous system (CNS) abnormality in males, including stable subclinical signs and, less often, short-duration episodes characterized by motor difficulties and altered consciousness. However, some mutations have no apparent CNS effects. What distinguishes mutations with and without CNS manifestations has been unclear. Here we studied a total of 14 Cx32 mutations, 10 of which are associated with florid episodic CNS clinical syndromes in addition to peripheral neuropathy. The other 4 mutations exhibit neuropathy without clinical or subclinical CNS abnormalities. These “PNS-only” mutations (Y151C, V181M, R183C and L239I) form gap junction plaques and produce levels of junctional coupling similar to those for wild-type Cx32. In contrast, mutants with CNS manifestations (F51L, E102del, V139M, R142Q, R142W, R164W T55I, R164Q and C168Y) either form no morphological gap junction plaques or, if they do, produce little or no detectable junctional coupling. Thus, PNS and CNS abnormalities may involve different aspects of connexin function. PMID:28071741

  12. Fetal MRI in Prenatal Diagnosis of CNS Abnormalities

    J Gordon Millichap


    Full Text Available The value of fetal MRI (fMRI compared to ultrasound in the prenatal detection of CNS abnormalities and impact on counseling were determined in 25 pregnant women examined at University of Dusseldorf, Germany.

  13. CNS drug design: balancing physicochemical properties for optimal brain exposure.

    Rankovic, Zoran


    The human brain is a uniquely complex organ, which has evolved a sophisticated protection system to prevent injury from external insults and toxins. Designing molecules that can overcome this protection system and achieve optimal concentration at the desired therapeutic target in the brain is a specific and major challenge for medicinal chemists working in CNS drug discovery. Analogous to the now widely accepted rule of 5 in the design of oral drugs, the physicochemical properties required for optimal brain exposure have been extensively studied in an attempt to similarly define the attributes of successful CNS drugs and drug candidates. This body of work is systematically reviewed here, with a particular emphasis on the interplay between the most critical physicochemical and pharmacokinetic parameters of CNS drugs as well as their impact on medicinal chemistry strategies toward molecules with optimal brain exposure. A summary of modern CNS pharmacokinetic concepts and methods is also provided.

  14. Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

    Jacinta Nwamaka Nwogu


    Full Text Available Neurological complications associated with the human immunodeficiency virus (HIV are a matter of great concern. While antiretroviral (ARV drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity.

  15. Recurrence of autoimmune liver diseases after livertransplantation


    Liver transplantation (LT) is the most effective treatmentmodality for end stage liver disease caused by manyetiologies including autoimmune processes. That said,the need for transplantation for autoimmune hepatitis(AIH) and primary biliary cirrhosis (PBC), but not forprimary sclerosing cholangitis (PSC), has decreasedover the years due to the availability of effective medicaltreatment. Autoimmune liver diseases have superiortransplant outcomes than those of other etiologies. WhileAIH and PBC can recur after LT, recurrence is of limitedclinical significance in most, but not all cases. RecurrentPSC, however, often progresses over years to a stagerequiring re-transplantation. The exact incidence andthe predisposing factors of disease recurrence remaindebated. Better understanding of the pathogenesis andthe risk factors of recurrent autoimmune liver diseasesis required to develop preventive measures. In thisreview, we discuss the current knowledge of incidence,diagnosis, risk factors, clinical course, and treatmentof recurrent autoimmune liver disease (AIH, PBC, PSC)following LT.

  16. CNS Involvement in AML Patient Treated with 5-Azacytidine

    Diamantina Vasilatou


    Full Text Available Central nervous system (CNS involvement in acute myeloid leukemia (AML is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status.

  17. An instructive case of CNS histoplasmosis in an immunocompetent host.

    Ramireddy, Sweeya; Wanger, Audrey; Ostrosky, Luis


    Histoplasma capsulatum is a dimorphic endemic fungus which infects both immunocompetent and immunocompromised hosts. Isolated CNS histoplasmosis is a rare presentation with increased risk in individuals with impaired cellular immunity, however not all patients with this condition are immunocompromised. We report a case of isolated CNS histoplasmosis in an otherwise healthy immunocompetent patient who was initially treated with Liposomal Amphotericin B followed by oral Voriconazole and later Itraconazole with significant improvement in clinical status.

  18. [Thoracoscopic treatment of recurrent pneumothorax].

    Suter, M; Berner, M; Vandoni, R; Cuttat, J F


    Spontaneous pneumothorax (PNO) is usually due to rupture of a small subpleural bleb into the pleural cavity and affects mainly young men. After simple drainage, recurrence occurs in about 50% of cases. The risk of recurrence increases after each new PNO. Secondary PNO complicates an underlying pulmonary disease, especially chronic obstructive pulmonary disease with emphysema. A new form of secondary PNO has emerged in the recent years in AIDS patients with pneumocystis carinii pneumonia. We have shifted to a thoracoscopic therapy of PNO since May 1991. 25 PNO in 24 patients (1 bilateral) have been treated since that time up to April 1993. 19 PNO were primary, whereas 6 were secondary, included 3 iatrogenic PNO. Resection of the leaking parenchymal area was performed in 20 patients, and parietal partial pleurectomy was done in 20 cases. In the remaining cases, fibrin glue was applied on the lesion and in 3 cases, chemical pleurodesis was attempted using silver nitrate or talc. 1 AIDS patient died of ARDS. 3 patients had recurrent PNO and had thoracotomy without complication. 21 patients did well. Partial PNO recurred in one of them 4 months later, and was treated by simple needle aspiration. Thoracoscopy is a useful method to treat recurrent or persistent spontaneous PNO. After only 25 cases, our success rate in primary PNO is 90%. There should be a learning curve. On the basis of our experience, we believe that recognition of the lesion and its resection as well as apical parietal pleurectomy are necessary to obtain good results and a low recurrence rate.

  19. Insights into the Physiological Role of CNS Regeneration Inhibitors

    Katherine Therese Baldwin


    Full Text Available The growth inhibitory nature of injured adult mammalian central nervous system (CNS tissue constitutes a major barrier to robust axonal outgrowth and functional recovery following trauma or disease. Prototypic CNS regeneration inhibitors are broadly expressed in the healthy and injured brain and spinal cord and include myelin-associated glycoprotein (MAG, the reticulon family member NogoA, oligodendrocyte myelin glycoprotein (OMgp, and chondroitin sulfate proteoglycans (CSPGs. These structurally diverse molecules strongly inhibit neurite outgrowth in vitro, and have been most extensively studied in the context of nervous system injury in vivo. The physiological role of CNS regeneration inhibitors in the naïve, or uninjured, CNS remains less well understood, but has received growing attention in recent years and is the focus of this review. CNS regeneration inhibitors regulate myelin development and axon stability, consolidate neuronal structure shaped by experience, and limit activity-dependent modification of synaptic strength. Altered function of CNS regeneration inhibitors is associated with neuropsychiatric disorders, suggesting crucial roles in brain development and health.

  20. The role of inflammation in CNS injury and disease.

    Lucas, Sian-Marie; Rothwell, Nancy J; Gibson, Rosemary M


    For many years, the central nervous system (CNS) was considered to be 'immune privileged', neither susceptible to nor contributing to inflammation. It is now appreciated that the CNS does exhibit features of inflammation, and in response to injury, infection or disease, resident CNS cells generate inflammatory mediators, including proinflammatory cytokines, prostaglandins, free radicals and complement, which in turn induce chemokines and adhesion molecules, recruit immune cells, and activate glial cells. Much of the key evidence demonstrating that inflammation and inflammatory mediators contribute to acute, chronic and psychiatric CNS disorders is summarised in this review. However, inflammatory mediators may have dual roles, with detrimental acute effects but beneficial effects in long-term repair and recovery, leading to complications in their application as novel therapies. These may be avoided in acute diseases in which treatment administration might be relatively short-term. Targeting interleukin (IL)-1 is a promising novel therapy for stroke and traumatic brain injury, the naturally occurring antagonist (IL-1ra) being well tolerated by rheumatoid arthritis patients. Chronic disorders represent a greater therapeutic challenge, a problem highlighted in Alzheimer's disease (AD); significant data suggested that anti-inflammatory agents might reduce the probability of developing AD, or slow its progression, but prospective clinical trials of nonsteroidal anti-inflammatory drugs or cyclooxygenase inhibitors have been disappointing. The complex interplay between inflammatory mediators, ageing, genetic background, and environmental factors may ultimately regulate the outcome of acute CNS injury and progression of chronic neurodegeneration, and be critical for development of effective therapies for CNS diseases.

  1. Successful Treatment of Posttransplant EBV-Associated Lymphoma and Plasmacytoma Solely Localized to the CNS

    Per Boye Hansen


    Full Text Available Two patients with diabetic nephropathy were diagnosed with primary central nervous system posttransplant Epstein-Barr-virus-associated lymphoproliferative disorder (PTLD 3 years after renal transplantation. The histological diagnoses of the isolated brain tumors were diffuse large B-cell lymphoma and plasmacytoma. Considerable co-morbidity precluded intensive chemotherapy. The first patient with lymphoid CD20+ PTLD had a partial resection of her tumor performed. She was treated with 4 weekly doses of rituximab, ganciclovir and prednisolone; the posttransplant immune suppression (tacrolimus was reduced. After 4 weeks of treatment a magnetic resonance imaging (MRI demonstrated complete regression of the CNS lesion. The patient continues to receive rituximab (every second month, valgangciclovir and low-dose prednisolone. Twenty-two months after initiation of therapy, she is still in complete remission. The second patient was only treated with craniospinal irradiation involving the medulla to the second cervical vertebra and valgangciclovir. Moreover, the posttransplant immune suppression was reduced. A new MRI two months after initiation of therapy showed a complete regression of the lesions in the CNS; this was again demonstrated by a MRI after 19 months. These 2 cases illustrate interesting alternative treatments of PTLD. To our knowledge, an EBV-associated PTLD of plasmacytic origin isolated to the CNS has never been described before.

  2. Microglial responses around intrinsic CNS neurons are correlated with axonal regeneration

    Tohyama Koujiro


    Full Text Available Abstract Background Microglia/macrophages and lymphocytes (T-cells accumulate around motor and primary sensory neurons that are regenerating axons but there is little or no microglial activation or T-cell accumulation around axotomised intrinsic CNS neurons, which do not normally regenerate axons. We aimed to establish whether there was an inflammatory response around the perikarya of CNS neurons that were induced to regenerate axons through a peripheral nerve graft. Results When neurons of the thalamic reticular nucleus (TRN and red nucleus were induced to regenerate axons along peripheral nerve grafts, a marked microglial response was found around their cell bodies, including the partial enwrapping of some regenerating neurons. T-cells were found amongst regenerating TRN neurons but not rubrospinal neurons. Axotomy alone or insertion of freeze-killed nerve grafts did not induce a similar perineuronal inflammation. Nerve grafts in the corticospinal tracts did not induce axonal regeneration or a microglial or T-cell response in the motor cortex. Conclusions These results strengthen the evidence that perineuronal microglial accumulation (but not T-cell accumulation is involved in axonal regeneration by intrinsic CNS and other neurons.

  3. Microglial responses around intrinsic CNS neurons are correlated with axonal regeneration.

    Shokouhi, Bahman N; Wong, Bernadette Z Y; Siddiqui, Samir; Lieberman, A Robert; Campbell, Gregor; Tohyama, Koujiro; Anderson, Patrick N


    Microglia/macrophages and lymphocytes (T-cells) accumulate around motor and primary sensory neurons that are regenerating axons but there is little or no microglial activation or T-cell accumulation around axotomised intrinsic CNS neurons, which do not normally regenerate axons. We aimed to establish whether there was an inflammatory response around the perikarya of CNS neurons that were induced to regenerate axons through a peripheral nerve graft. When neurons of the thalamic reticular nucleus (TRN) and red nucleus were induced to regenerate axons along peripheral nerve grafts, a marked microglial response was found around their cell bodies, including the partial enwrapping of some regenerating neurons. T-cells were found amongst regenerating TRN neurons but not rubrospinal neurons. Axotomy alone or insertion of freeze-killed nerve grafts did not induce a similar perineuronal inflammation. Nerve grafts in the corticospinal tracts did not induce axonal regeneration or a microglial or T-cell response in the motor cortex. These results strengthen the evidence that perineuronal microglial accumulation (but not T-cell accumulation) is involved in axonal regeneration by intrinsic CNS and other neurons.

  4. Fuzzy recurrence plots

    Pham, T. D.


    Recurrence plots display binary texture of time series from dynamical systems with single dots and line structures. Using fuzzy recurrence plots, recurrences of the phase-space states can be visualized as grayscale texture, which is more informative for pattern analysis. The proposed method replaces the crucial similarity threshold required by symmetrical recurrence plots with the number of cluster centers, where the estimate of the latter parameter is less critical than the estimate of the former.

  5. Cediranib Maleate in Treating Patients With Recurrent or Newly Diagnosed Metastatic Head and Neck Cancer


    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IV Laryngeal Squamous Cell Carcinoma; Stage IV Laryngeal Verrucous Carcinoma; Stage IV Lip and Oral Cavity Squamous Cell Carcinoma; Stage IV Major Salivary Gland Carcinoma; Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IV Oral Cavity Verrucous Carcinoma; Stage IV Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

  6. Recurrent zosteriform herpes simplex

    Inamadar Arun


    Full Text Available A 25-year-old man had recurrent zosteriform herpes simplex for past 6 years. The attacks were precipitated by prolonged exposure to sunlight. Pain was mild and lesions used to subside each time in about 7 days. Clinical features which help in differentiating recurrent herpes simplex from recurrent herpes zoster are summarized.

  7. Corrosion Behavior of Ferritic/Martensitic Steels CNS-I and Modified CNS-II in Supercritical Water

    YANG Ying; YAN Qing-zhi; YANG Ya-feng; ZHANG Le-fu; GE Chang-chun


    The corrosion behaviors of CNS-I and modified CNS-II were evaluated by exposing to superciritical water (SCW) at 550℃ and 25 MPa with a dissolved oxygen concentration of 200× 10 ^-9 for up to 1 000 h. Detailed corrosion results of these two alloys were provided, including the growth rate of the oxide scales, microstructure of the oxide scales, distribution of phases and alloying elements. The mass gains of CNS-I and modified CNS-II were 609.73 mg/dm2 and 459.42 mg/dm2 , respectively, after exposing to SCW for 1 000 h. A duplex oxide scale with an outer porous magnetite layer and an inner relatively dense magnetite/spinel-mixed layer was identified on CNS-I and modified CNS-II after the test. The oxide scales were rather porous at the beginning of the test but the porosity decreased with increase of the exposure duration. It was found that Fe was enriched in the outer oxide layer, Cr was enriched in the inner oxide layer and O existed at a very high concnetration in the whole oxide scale. Other alloying elements such as Mo, W, Mn were depleted from the outer oxide layer and showed slightly enrichment in the inner oxide layer. The distributution of Ni was different from other elements, it was enriched in the interface bewteen the base metal and the oxide scale and depleted in the outer and inner oxide layers.

  8. A beta-lactam antibiotic dampens excitotoxic inflammatory CNS damage in a mouse model of multiple sclerosis.

    Nico Melzer

    Full Text Available In multiple sclerosis (MS and its animal model experimental autoimmune encephalomyelitis (EAE, impairment of glial "Excitatory Amino Acid Transporters" (EAATs together with an excess glutamate-release by invading immune cells causes excitotoxic damage of the central nervous system (CNS. In order to identify pathways to dampen excitotoxic inflammatory CNS damage, we assessed the effects of a beta-lactam antibiotic, ceftriaxone, reported to enhance expression of glial EAAT2, in "Myelin Oligodendrocyte Glycoprotein" (MOG-induced EAE. Ceftriaxone profoundly ameliorated the clinical course of murine MOG-induced EAE both under preventive and therapeutic regimens. However, ceftriaxone had impact neither on EAAT2 protein expression levels in several brain areas, nor on the radioactive glutamate uptake capacity in a mixed primary glial cell-culture and the glutamate-induced uptake currents in a mammalian cell line mediated by EAAT2. Moreover, the clinical effect of ceftriaxone was preserved in the presence of the EAAT2-specific transport inhibitor, dihydrokainate, while dihydrokainate alone caused an aggravated EAE course. This demonstrates the need for sufficient glial glutamate uptake upon an excitotoxic autoimmune inflammatory challenge of the CNS and a molecular target of ceftriaxone other than the glutamate transporter. Ceftriaxone treatment indirectly hampered T cell proliferation and proinflammatory INFgamma and IL17 secretion through modulation of myelin-antigen presentation by antigen-presenting cells (APCs e.g. dendritic cells (DCs and reduced T cell migration into the CNS in vivo. Taken together, we demonstrate, that a beta-lactam antibiotic attenuates disease course and severity in a model of autoimmune CNS inflammation. The mechanisms are reduction of T cell activation by modulation of cellular antigen-presentation and impairment of antigen-specific T cell migration into the CNS rather than or modulation of central glutamate homeostasis.

  9. Clinical and immunologic features of recurrent herpes zoster (HZ).

    Nakamura, Yuki; Miyagawa, Fumi; Okazaki, Aiko; Okuno, Yoshinobu; Mori, Yasuko; Iso, Hiroyasu; Yamanishi, Koichi; Asada, Hideo


    Recurrent herpes zoster (HZ) is thought to be rare, but there have been few large-scale studies of recurrent HZ. We conducted a large-scale prospective cohort study to characterize recurrent HZ. We examined 12,522 participants aged 50 years or older in Shozu County and followed them up for 3 years. We compared the incidence of HZ and postherpetic neuralgia, severity of skin lesions and acute pain, cell-mediated immunity, and varicella-zoster virus-specific antibody titer between primary and recurrent HZ. A total of 401 participants developed HZ: 341 with primary HZ and 60 with recurrent HZ. Skin lesions and acute pain were significantly milder and the incidence of postherpetic neuralgia was lower in patients aged 50 to 79 years with recurrent HZ than in those with primary HZ. Varicella-zoster virus skin test induced a stronger reaction in patients aged 50 to 79 years with recurrent HZ than in those with primary HZ. Information on previous HZ episodes was self-reported by participants, so it could not be confirmed that they actually had a history of HZ. Recurrent HZ was associated with milder clinical symptoms than primary HZ, probably because of stronger varicella-zoster virus-specific cell-mediated immunity in the patients with recurrence. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  10. Primary leptomeningeal lymphoma

    Taylor, Jennie W.; Flanagan, Eoin P.; O'Neill, Brian P.; Siegal, Tali; Omuro, Antonio; DeAngelis, Lisa; Baehring, Joachim; Nishikawa, Ryo; Pinto, Fernando; Chamberlain, Marc; Hoang-Xuan, Khe; Gonzalez-Aguilar, Alberto; Batchelor, Tracy; Blay, Jean-Yves; Korfel, Agnieszka; Betensky, Rebecca A.; Lopes, Maria-Beatriz S.


    Objective: To evaluate clinical presentation, optimal diagnostic evaluation and treatment, and outcome in primary leptomeningeal lymphoma, a rare form of primary CNS lymphoma without parenchymal or systemic involvement. Methods: The International Primary CNS Lymphoma Collaborative Group, a multidisciplinary group of physicians with a particular interest in primary CNS lymphoma, retrospectively identified cases of lymphoma isolated to the leptomeninges as diagnosed by CSF cytology, flow cytometry, or biopsy, without systemic or parenchymal brain/spinal cord lymphoma or immunodeficiency. Results: Forty-eight patients were identified, with median age at diagnosis of 51 years and median Eastern Cooperative Oncology Group performance status of 2. Presenting symptoms were multifocal in 68%. Leptomeningeal enhancement was seen in 74% and CSF profile was abnormal in all cases. CSF cytology detected malignant lymphocytes in 67%. Flow cytometry identified monoclonal population in 80%, as did receptor gene rearrangement studies in 71%. Sixty-two percent had B-cell lymphoma, 19% T-cell, and 19% unclassified. Treatment varied and included fractionated radiotherapy (36%), systemic chemotherapy (78%), and intra-CSF chemotherapy (66%), with 66% receiving ≥2 modalities. Seventy-one percent had a favorable clinical response; ultimately, 44% received salvage treatment. Median overall survival was 24 months, with 11 patients still alive at 50 months follow-up. Conclusion: Primary leptomeningeal lymphoma is a rare form of primary CNS lymphoma. Patients usually present with multifocal symptoms, with evidence of leptomeningeal enhancement and diagnostic CSF analysis. Although treatment is highly variable, patients have a better prognosis than previously reported and a subset may be cured. PMID:24107866

  11. Risk of Local Recurrence of Benign and Borderline Phyllodes Tumors

    Borhani-Khomani, Kaveh; Talman, Maj-Lis Møller; Kroman, Niels


    PURPOSE: To determine the recurrence rate of benign and borderline phyllodes tumors (PTs) of the breast, the association between the size of resection margin and risk of recurrence and the risk of progression of histological grading at recurrence. METHODS: Nationwide retrospective study on Danish...... in histological grading was found. The results do not justify wide excision margins of nonmalignant phyllodes tumors of the breast....... women aged 18 years or older, operated from 1999 to 2014, with resected benign or borderline PTs. Information on age, size of primary tumor and recurrence, histological grade, surgical treatment, margin size, and local recurrence were collected from the national Danish Pathology Register. RESULTS...

  12. Percutaneous needle fasciotomy for recurrent Dupuytren disease.

    van Rijssen, Annet L; Werker, Paul M N


    Increasing options to treat Dupuytren disease include percutaneous needle fasciotomy (PNF), a minimally invasive technique that has proven to be effective for the treatment of primary disease. However, its effect on recurrent disease is not clear. We studied 30 patients with recurrent Dupuytren disease in 40 fingers, with a mean follow-up of 4.4 years. Primary outcome measures were total passive extension deficit reduction and interval to a second recurrence, defined as an increase of more than 30° compared with the result at the end of the previous treatment. We noted complications. Total passive extension reduction was 76%. Percutaneous needle fasciotomy was especially effective for the metacarpophalangeal joint, with an average reduction of 93%, whereas the average reduction in the proximal interphalangeal joint was 57%. A total of 50% of patients did not develop a secondary recurrence during follow-up. The other 50% did, and we treated recurrence within an average of 1.4 years after PNF. By means of PNF, we postponed tertiary treatment an average of 2.9 years starting from the initial treatment for Dupuytren disease. We successfully treated all secondary recurrences by limited fasciectomy, according to patients' wishes. We noted no major adverse effects. Percutaneous needle fasciotomy can be applied effectively for recurrent disease; 50% of patients remain free of recurrence for a mean of 4.4 years. If a secondary recurrence occurs, it does so relatively early after treatment. Patients must therefore be willing to accept this uncertainty in the context of the advantages of PNF, such as fast recovery, low complication rate, and minimal invasiveness. Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  13. CNS Anticancer Drug Discovery and Development Conference White Paper.

    Levin, Victor A; Tonge, Peter J; Gallo, James M; Birtwistle, Marc R; Dar, Arvin C; Iavarone, Antonio; Paddison, Patrick J; Heffron, Timothy P; Elmquist, William F; Lachowicz, Jean E; Johnson, Ted W; White, Forest M; Sul, Joohee; Smith, Quentin R; Shen, Wang; Sarkaria, Jann N; Samala, Ramakrishna; Wen, Patrick Y; Berry, Donald A; Petter, Russell C


    Following the first CNS Anticancer Drug Discovery and Development Conference, the speakers from the first 4 sessions and organizers of the conference created this White Paper hoping to stimulate more and better CNS anticancer drug discovery and development. The first part of the White Paper reviews, comments, and, in some cases, expands on the 4 session areas critical to new drug development: pharmacological challenges, recent drug approaches, drug targets and discovery, and clinical paths. Following this concise review of the science and clinical aspects of new CNS anticancer drug discovery and development, we discuss, under the rubric "Accelerating Drug Discovery and Development for Brain Tumors," further reasons why the pharmaceutical industry and academia have failed to develop new anticancer drugs for CNS malignancies and what it will take to change the current status quo and develop the drugs so desperately needed by our patients with malignant CNS tumors. While this White Paper is not a formal roadmap to that end, it should be an educational guide to clinicians and scientists to help move a stagnant field forward. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail:

  14. Isolated vasculitis of the CNS; Isolierte Vaskulitis des ZNS

    Block, F. [RWTH Aachen (Germany). Neurologische Klinik; Reith, W. [Universitaet des Saarlandes, Homburg/Saar (Germany). Radiologische Klinik


    Vasculitis is a rare cause for disease of the CNS. The isolated vasculitis of the CNS is restricted to the CNS whereas other forms of vasculitis affect various organs including the CNS. Headache, encephalopathy, focal deficits and epileptic seizures are the major symptoms suggestive for vasculitis. One major criterion of the isolated vasculitis of the CNS is the lack of evidence for other vasculitis forms or for pathology of other organs. Angiography displays multifocal segmental stenosis of intracranial vessels. MRI demonstrates multiple lesions which in part show enhancement after gadolinium. A definite diagnosis can only be made on the grounds of biopsy from leptomeninges and parenchyma. Therapy consists of corticosteroids and cyclophosphamid. (orig.) [German] Vaskulitiden sind eine seltene Ursache fuer Erkrankungen des ZNS. Die Vaskulitiden lassen sich in primaere und sekundaere einteilen, von denen sich die ueberwiegende Mehrzahl an verschiedenen Organsystemen einschliesslich dem ZNS manifestieren kann. Die isolierte ZNS-Vaskulitis ist auf das ZNS beschraenkt, bei ihr stehen klinisch-neurologisch wie bei den anderen Vaskulitisformen Kopfschmerzen, Enzephalopathie, fokale Defizite und epileptische Anfaelle im Vordergrund. Ein Kriterium der isolierten ZNS-Vaskulitis ist der klinische und laborchemische Ausschluss anderer Vaskulitiden bzw. der Beteiligung anderer Organsysteme. Multiple Kaliberspruenge intrakranieller Arterien in der zerebralen Angiographie und multiple, kleine, z.T. kontrastmittelaufnehmende Laesionen in der MRT des Schaedels sind vaskulitistypische Befunde, die allerdings auch bei anderen Vaskulitiden zu finden sind. Einzig beweisend ist eine Hirnhaut- und Hirnparenchymbiopsie. Besonders vor dem Hintergrund der therapeutischen Option, Immunsuppression mit Kortison und Cyclophosphamid, ist eine moeglichst genaue Diagnose erforderlich. (orig.)

  15. Primary Renal Synovial Sarcoma With Recurrence and Metastasis%原发性肾滑膜肉瘤及术后复发、转移的影像学表现

    李炯佾; 曹文娟; 杨呈伟; 崔久法; 王林; 彭国辉; 李秉诚; 孙伟; 张维明; 张浩


    Objective To discuss the imaging features of primary renal synovial sarcoma(PRSS)with recurrence and tastasis and improve its diagnostic accuracy. Materials and Methods The clinical, imaging and pathology findings, im-munohistochemistry (IHC) of 1 patient with PRSS were retrospectively analyzed, and the literature was reviewed to evaluate the relationships between the imaging signs, clinical and pathologic findings. Results CT scan: A mass lesion with indistinguishable borders to the kidney, rooting from the right kidney and extending to the inferior and medial aspect anterior to the psoas muscle, about 10.7 cm × 12.3 cm × 15. 5 cm, demonstrating a tabular contour and including cystic areas was detected on CT. No additional tumor, lung metastases.paracaval or paraaortic lymph nodes were detected on CT. A hypoecho-ic solid mass lesion extending from the lower pole of the right kidney to the inferior and medial aspect, about 13.5 cm × 11.1 cm × 10.5 cm, demonstrating a tabular contour including cystic areas and star point like flow signals was seen on the ultrasonic examination. The diagnosis of PRSS in the patient was confirmed by postoperative pathology. Under microscope, tumor was typically mitotically active,monomorphic spindle cells growing in intersecting fascicles or in solid sheets with epithelial differentiation. In some areas a haemangiopericytoma like pattern was found. IHC showed that the tumor cells were positive for the markers Vimentin, CD 99 and Bel 2, but CK was negative. The patient died of local recurrence and multi-metastasis in 8 months after surgery. Conclusion PRSS is extremely rare and malignant tumor with poor prognosis. There are some relatively specific imaging findings, however its diagnosis is depend on pathology, IHC and SYT-SSX gene detection. It has been demonstrated that the use of CT in the diagnosis and the evaluation of the staging of the PRSS is useful by defining lymph node involvement, distant metastases, and local

  16. Identification of new therapeutic targets for prevention of CNS inflammation

    Owens, Trevor


    Multiple sclerosis (MS) is a disease of complex pathologies, which involves infiltration by CD4(+) and CD8(+) T cells of and response within the central nervous system. Expression in the CNS of cytokines, reactive nitrogen species and costimulator molecules have all been described in MS. Notably......, the cytokines IFN-gamma and TNF are strongly expressed. Microglial cells in the CNS express costimulator molecules and it is assumed that they play a role in directing or inducing the T cell response. Transgenic experiments have tested the effects of overexpression of these molecules in mice and have shown...... via the enzyme inducible nitric oxide synthase, which is immunosuppressive, IFN-gamma is predominantly pro-inflammatory. In CNS disease in mice that involves CD8(+) T cells, IFN-gamma blockade is protective. Finally, microglial expression of the costimulator ligand B7.2 induces demyelinating pathology...

  17. Glial connexins and gap junctions in CNS inflammation and disease.

    Kielian, Tammy


    Gap junctions facilitate direct cytoplasmic communication between neighboring cells, facilitating the transfer of small molecular weight molecules involved in cell signaling and metabolism. Gap junction channels are formed by the joining of two hemichannels from adjacent cells, each composed of six oligomeric protein subunits called connexins. Of paramount importance to CNS homeostasis are astrocyte networks formed by gap junctions, which play a critical role in maintaining the homeostatic regulation of extracellular pH, K+, and glutamate levels. Inflammation is a hallmark of several diseases afflicting the CNS. Within the past several years, the number of publications reporting effects of cytokines and pathogenic stimuli on glial gap junction communication has increased dramatically. The purpose of this review is to discuss recent observations characterizing the consequences of inflammatory stimuli on homocellular gap junction coupling in astrocytes and microglia as well as changes in connexin expression during various CNS inflammatory conditions.

  18. Prospects for the development of epigenetic drugs for CNS conditions.

    Szyf, Moshe


    Advances in our understanding of the epigenetic mechanisms that control gene expression in the central nervous system (CNS) and their role in neuropsychiatric disorders are paving the way for a potential new therapeutic approach that is focused on reversing the epigenetic underpinnings of neuropsychiatric conditions. In this article, the complexity of epigenetic processes and the current level of proof for their involvement in CNS disorders are discussed. The preclinical evidence for efficacy of pharmacological approaches that target epigenetics in the CNS and the particular challenges of this approach are also examined. Finally, strategies to address these challenges through the development of improved evidence-based epigenetic therapeutics and through combining pharmacological and behavioural approaches are presented.

  19. Disruption of microtubule integrity initiates mitosis during CNS repair.

    Bossing, Torsten; Barros, Claudia S; Fischer, Bettina; Russell, Steven; Shepherd, David


    Mechanisms of CNS repair have vital medical implications. We show that traumatic injury to the ventral midline of the embryonic Drosophila CNS activates cell divisions to replace lost cells. A pilot screen analyzing transcriptomes of single cells during repair pointed to downregulation of the microtubule-stabilizing GTPase mitochondrial Rho (Miro) and upregulation of the Jun transcription factor Jun-related antigen (Jra). Ectopic Miro expression can prevent midline divisions after damage, whereas Miro depletion destabilizes cortical β-tubulin and increases divisions. Disruption of cortical microtubules, either by chemical depolymerization or by overexpression of monomeric tubulin, triggers ectopic mitosis in the midline and induces Jra expression. Conversely, loss of Jra renders midline cells unable to replace damaged siblings. Our data indicate that upon injury, the integrity of the microtubule cytoskeleton controls cell division in the CNS midline, triggering extra mitosis to replace lost cells. The conservation of the identified molecules suggests that similar mechanisms may operate in vertebrates.

  20. Therapeutic immune clearance of rabies virus from the CNS

    Hooper, D Craig; Roy, Anirban; Kean, Rhonda B; Phares, Timothy W; Barkhouse, Darryll A


    The long-held concept that rabies infection is lethal in humans once the causative rabies virus has reached the CNS has been called into question by the recent survival of a number of patients with clinical rabies. Studies in animal models provide insight into why survival from a rabies virus infection that has spread to the CNS is possible and the immune mechanisms involved. In the CNS, both innate mechanisms capable of inhibiting virus replication and the activity of infiltrating rabies virus-specific T and B cells with the capacity to clear the virus are required. Deficiencies in the induction of either aspect of rabies immunity can lead to lethal consequences but may be overcome by novel approaches to active and passive immunization. PMID:21686076

  1. Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

    Alerie Guzman De La Fuente


    Full Text Available The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.

  2. Late recurrence of medulloblastoma.

    Stevens, Brittney; Razzaqi, Faisal; Yu, Lolie; Craver, Randall


    We present a child with a cerebellar medulloblastoma, diagnosed at age three, treated with near total surgical resection, radiotherapy, and chemotherapy, that recurred 13 years after the initial diagnosis. This late recurrence exceeds the typical 10-year survival statistics that are in common use, and exceeds the Collins rule. Continued follow-up of these children is justified to increase the likelihood of detecting these late recurrences early and to learn more about these late recurrences.

  3. CNS Metastases from Bone and Soft Tissue Sarcomas in Children, Adolescents, and Young Adults: Are They Really So Rare?

    Monika Bekiesinska-Figatowska


    Full Text Available Purpose. To check whether primary involvement of brain/spinal cord by bone/soft tissue sarcomas’ metastases in children is as rare as described and to present various morphological forms of bone/soft tissue sarcomas’ CNS metastases. Methods. Patients with first diagnosis in 1999–2014 treated at single center were included with whole course of disease evaluation. Brain/spinal canal magnetic resonance imaging (MRI/computed tomography were performed in cases suspicious for CNS metastases. Extension from skull/vertebral column metastases was excluded. Results. 550 patients were included. MRI revealed CNS metastases in 19 patients (incidence 3.45%, 14 boys, aged 5–22 years. There were 12/250 osteosarcoma cases, 2/200 Ewing’s sarcoma, 1/50 chondrosarcoma, 3/49 rhabdomyosarcoma (RMS, and 1/1 malignant mesenchymoma. There were 10 single metastases and 7 cases of multiple ones; in 2 RMS cases only leptomeningeal spread in brain and spinal cord was found. Calcified metastases were found in 3 patients and hemorrhagic in 4. In one RMS patient there were numerous solid, cystic, hemorrhagic lesions and leptomeningeal spread. Conclusions. CNS metastases are rare and late in children with bone/soft tissue sarcomas, although in our material more frequent (3.45% than in other reports (0.7%. Hematogenous spread to brain and hemorrhagic and calcified lesions dominated in osteosarcoma. Ewing sarcoma tended to metastasize to skull bones. Soft tissue sarcomas presented various morphological forms.

  4. CNS Metastases from Bone and Soft Tissue Sarcomas in Children, Adolescents, and Young Adults: Are They Really So Rare?

    Duczkowska, Agnieszka; Duczkowski, Marek; Bragoszewska, Hanna; Romaniuk-Doroszewska, Anna; Iwanowska, Beata; Szkudlinska-Pawlak, Sylwia; Madzik, Jaroslaw; Bilska, Katarzyna; Raciborska, Anna


    Purpose. To check whether primary involvement of brain/spinal cord by bone/soft tissue sarcomas' metastases in children is as rare as described and to present various morphological forms of bone/soft tissue sarcomas' CNS metastases. Methods. Patients with first diagnosis in 1999–2014 treated at single center were included with whole course of disease evaluation. Brain/spinal canal magnetic resonance imaging (MRI)/computed tomography were performed in cases suspicious for CNS metastases. Extension from skull/vertebral column metastases was excluded. Results. 550 patients were included. MRI revealed CNS metastases in 19 patients (incidence 3.45%), 14 boys, aged 5–22 years. There were 12/250 osteosarcoma cases, 2/200 Ewing's sarcoma, 1/50 chondrosarcoma, 3/49 rhabdomyosarcoma (RMS), and 1/1 malignant mesenchymoma. There were 10 single metastases and 7 cases of multiple ones; in 2 RMS cases only leptomeningeal spread in brain and spinal cord was found. Calcified metastases were found in 3 patients and hemorrhagic in 4. In one RMS patient there were numerous solid, cystic, hemorrhagic lesions and leptomeningeal spread. Conclusions. CNS metastases are rare and late in children with bone/soft tissue sarcomas, although in our material more frequent (3.45%) than in other reports (0.7%). Hematogenous spread to brain and hemorrhagic and calcified lesions dominated in osteosarcoma. Ewing sarcoma tended to metastasize to skull bones. Soft tissue sarcomas presented various morphological forms.

  5. Recurrent intracerebral hemorrhage

    Shen jinsong; Lu jianhong


    Objective: In order to study the clinical manifestation and risk factor of recurrent intracerebral hemorrhage(ICH).Methods:The 256 patients were analysed who admitted to our hospital for intracerebral hemorrhage between 1995 and 1997.The 15(5 .86%)patients had a recurrent ICH.There were 9 men and 6 women and the mean age of the patients was 63.5 ± 6.4years at the first bleeding episode and 67.8± 8. 5 years at the second. The mean interval between the two bleeding episodes was 44.6 ± 12.5 months. The 73.3%patients were hypertensive .′The site of the first hemorrhage was ganglionic in 8 patients , ]ohar in six paients and brainstem in one .The recurrent hemorrhage occurred at a different location from the previous ICH.The most common pattern of recurrence was “ganglionic -ganglionic” (7 patients), lobar - ganglionic (3 patients), lobar-lobar(three patients), which was always observed in hypertensive patients. The outcome after the recurrent hemorrhage was usually poor. By comparison with 24 patients followed up to average 47.5± 18.7 months with isolated ICH without recurrence .Only lobar hematoma and a younger age were risk factors for recurrences whereas sex and previous hypertension were not. The mechanism of recurrence of ICH were multiple(hypertension, cerebral amyloid angiopathy).Contral of blood pressure and good living habit after the first hemorrhage may prevent ICH recurrences.

  6. Optimal Recurrence Grammars

    Graben, Peter beim; Fröhlich, Flavio


    We optimally estimate the recurrence structure of a multivariate time series by Markov chains obtained from recurrence grammars. The goodness of fit is assessed with a utility function derived from the stochastic Markov transition matrix. It assumes a local maximum for the distance threshold of the optimal recurrence grammar. We validate our approach by means of the nonlinear Lorenz system and its linearized stochastic surrogates. Finally we apply our optimization procedure to the segmentation of neurophysiological time series obtained from anesthetized animals. We propose the number of optimal recurrence domains as a statistic for classifying an animals' state of consciousness.

  7. Tumor vaccine against recurrence of hepatocellular carcinoma

    Bao-Gang Peng; Li-Jiang Liang; Qiang He; Ming Kuang; Jia-Ming Lia; Ming-De Lu; Jie-Fu Huang


    AIM: To investigate the effects of autologous tumor vaccine on recurrence of hepatocellular carcinoma (HCC).METHODS: Sixty patients with HCC who had undergone curative resection, were randomly divided into HCC vaccine group and control group. Three vaccinations at 2-wk intervals were performed after curative hepatic resection. Delayedtype- hypersensitivity (DTH) test was performed before and after vaccination. Primary endpoints were the time of recurrence.RESULTS: Four patients in control group and 6 patients in HCC vaccine group were withdrawn from the study. The vaccine containing human autologous HCC fragments showed no essential adverse effect in a phase Ⅱ clinical trial and 17 of 24 patients developed a DTH response against the fragments. Three of 17 DTH-positive response patients and 5 of 7 DTH- negative response patients had recurrences after curative resection. After the operation,1-, 2- and 3-year recurrence rates of HCC vaccine groupwere 16.7%, 29.2% and 33.3%, respectively. But, 1-, 2- and3-year recurrence rates of the control group were 30.8%,53.8% and 61.5%, respectively. The time before the first recurrence in the vaccinated patients was significantly longer than that in the control patients (P<0.05).CONCLUSION: Autologous tumor vaccine is of promise in decreasing recurrence of human HCC.

  8. Tea and Recurrent Clostridium difficile Infection.

    Oman Evans Ii, Martin; Starley, Brad; Galagan, Jack Carl; Yabes, Joseph Michael; Evans, Sara; Salama, Joseph John


    Background and Aims. Studies have shown effects of diet on gut microbiota. We aimed to identify foods associated with recurrent Clostridium difficile infection (CDI). Methods. In this cross-sectional survey, consecutive patients diagnosed with CDI were identified by electronic medical records. Colitis symptoms and positive Clostridium difficile assay were confirmed. Health-care onset-health-care facility associated CDI was excluded. Food surveys were mailed to 411 patients. Survey responses served as the primary outcome measure. Spearman's rank correlation identified risk factors for CDI recurrence. Results. Surveys were returned by 68 patients. Nineteen patients experienced CDI recurrence. Compared to patients without CDI recurrence, patients with CDI recurrence had more antibiotics prescribed preceding their infection (p = 0.003). Greater numbers of the latter also listed tea (p = 0.002), coffee (p = 0.013), and eggs (p = 0.013), on their 24-hour food recall. Logistic regression identified tea as the only food risk factor for CDI recurrence (adjusted OR: 5.71; 95% CI: 1.26-25.89). Conclusion. The present results indicate a possible association between tea and CDI recurrence. Additional studies are needed to characterize and confirm this association.

  9. Recurrent Takotsubo Cardiomyopathy Related to Recurrent Thyrotoxicosis.

    Patel, Keval; Griffing, George T; Hauptman, Paul J; Stolker, Joshua M


    Takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome, is characterized by acute left ventricular dysfunction caused by transient wall-motion abnormalities of the left ventricular apex and mid ventricle in the absence of obstructive coronary artery disease. Recurrent episodes are rare but have been reported, and several cases of takotsubo cardiomyopathy have been described in the presence of hyperthyroidism. We report the case of a 55-year-old woman who had recurrent takotsubo cardiomyopathy, documented by repeat coronary angiography and evaluations of left ventricular function, in the presence of recurrent hyperthyroidism related to Graves disease. After both episodes, the patient's left ventricular function returned to normal when her thyroid function normalized. These findings suggest a possible role of thyroid-hormone excess in the pathophysiology of some patients who have takotsubo cardiomyopathy.

  10. Recurrent Omental Hemangiopericytoma: A Therapeutic Challenge

    Sara Jaber


    Full Text Available Hemangiopericytomas are vascular tumors with a susceptibility to arise anywhere in the human body. We present a case of a 68-year-old female with primary omental hemangiopericytoma and a two-time recurrence managed with surgery and close follow-up. The first recurrence was at 52 months and the second at 37 months following the prior presentation. No adjuvant chemotherapy or radiation therapy was administered. Given the widespread nature of the cell of origin, routine follow-up postoperatively with interval imaging in order to detect recurrences is imperative. Pathologic tumor characteristics may determine potential for recurrence and may also assist in determining whether adjuvant treatment modalities should be included in the management plan. Review of the English literature reveals a total of 24 cases of omental hemangiopericytomas inclusive of the current report.

  11. The risk of CNS involvement in aggressive lymphomas in the rituximab era.

    Benevolo, Giulia; Chiappella, Annalisa; Vitolo, Umberto


    The risk of CNS dissemination and CNS prophylaxis strategies in aggressive non-Hodgkin lymphoma (NHL) is still debated. CNS dissemination is a rare but fatal event. A CNS prophylaxis is common for Burkitt and B-cell lymphoblastic lymphoma; however, in other NHLs, prophylactic treatments are not systematically warranted. Current risk models showed low sensitivity in predicting CNS involvement, implying overtreatment in roughly 70% of high-risk patients. Risk models in the rituximab era were modulated for the detection of occult CNS disease at diagnosis using flow cytometry. The optimal regimen for CNS prophylaxis in aggressive lymphoma patients has not been established thus far and should be modulated at different levels of 'intensity' such as standard intrathecal chemotherapy, 'active' intrathecal chemotherapy with liposomal cytarabine or more aggressive systemic treatment with high doses of drugs having good CNS bioavailability reserved for patients who are truly at high risk of CNS dissemination.

  12. Dietoterapia en paciente con linfangiectasia intestinal primaria y ascitis quilosa de repetición Sucessful dietetic-therapy in primary intestinal lymphangiectasia and recurrent chylosa ascites: a case report

    C. Campos Martín


    Full Text Available Objetivos: La linfangiectasia intestinal primaria es un trastorno del sistema linfático, en el que debido a obstrucción del drenaje linfático se produce malabsorción, enteropatía pierde-proteínas e hipogammaglobulinemia, y consecuentemente una malnutrición en diverso grado. Su tratamiento es complejo e incluye medidas dietéticas y farmacológicas. Material y método: En este artículo se expone el caso de una mujer de 35 años con ascitis quilosa de repetición, precisando varios ingresos hospitalarios y paracentesis evacuadoras. Tras ser diagnosticada de linfangiectasia intestinal primaria, la instauración de dietoterapia sustituyendo las grasas alimentarias por aceite MCT, ha permitido una evolución favorable tanto desde el punto de vista clínico como analítico y antropométrico. Conclusiones: El empleo de una dieta específica y el uso de triglicéridos de cadena media en la linfangiectasia intestinal son el pilar principal del tratamiento en este caso, mejorando su sintomatología y estado nutricional. Precisa de alto nivel de adherencia y colaboración por parte del paciente, siendo necesario el control médico periódico de por vida, dado que la evolución a largo plazo no es bien conocida.Objectives: Primary intestinal lymphangiectasia is a lymphatic system's disorder, where lymphatic drainage is blockaged. Clinically it produces malabsorption, protein-losing enteropathy, hypogammaglobulin in blood, and several degrees of malnutrition. Its treatment is not easy and includes dietetic-therapy and drugs. Material and method: A 35-year-old-woman case report is exposed. She has recurrent chylosa ascites, requiring several admissions and evacuatory paracentesis. After food-fat was replaced by medium-chain triacylglicerol-enriched diet, a clinical, analytical and anthropometric improvement was demonstrated. Conclussions: The major way of treatment in intestinal lymphangiectasia in this case is the employement of specific-diet and

  13. Dynamics of chemosensitivity and chromosomal instability in recurrent glioblastoma

    Spiegl-Kreinecker, S.; Pirker, C; Marosi, C; Buchroithner, J; Pichler, J; Silye, R; Fischer, J.; Micksche, M.; Berger, W


    Glioblastoma multiforme is characterised by invasive growth and frequent recurrence. Here, we have analysed chromosomal changes in comparison to tumour cell aggressiveness and chemosensitivity of three cell lines established from a primary tumour and consecutive recurrences (BTL1 to BTL3) of a long-term surviving glioblastoma patient together with paraffin-embedded materials of five further cases with recurrent disease. Following surgery, the BTL patient progressed under irradiation/ lomustin...

  14. Endovascular management of recurrent adult coarctation of the aorta.

    Kpodonu, Jacques; Ramaiah, Venkatesh G; Rodriguez-Lopez, Julio A; Diethrich, Edward B


    Traditional open surgical repair has proven to be an effective treatment for the management of primary and recurrent coarctation of the thoracic aorta. Potential complications at short-term and long-term follow-up have included recurrent coarctation, hypertension, premature coronary artery disease, cerebrovascular disease, and anastomotic pseudoaneurysm. Endovascular repair of recurrent coarctation of the thoracic aorta offers a less invasive treatment approach in potential high-risk surgical patients.

  15. PET-CT in Determining the Radioembolization Dose Delivered to Patients With Liver Metastasis, Primary Liver Cancer, or Biliary Cancer


    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage D Adult Primary Liver Cancer (BCLC); Unspecified Adult Solid Tumor, Protocol Specific

  16. Recurrent Abdominal Pain

    Banez, Gerard A.; Gallagher, Heather M.


    The purpose of this article is to provide an empirically informed but clinically oriented overview of behavioral treatment of recurrent abdominal pain. The epidemiology and scope of recurrent abdominal pain are presented. Referral process and procedures are discussed, and standardized approaches to assessment are summarized. Treatment protocols…

  17. The eternal recurrence today

    Neves, J C S


    In this work we have carried out an approach between the nonsingular scientific cosmologies (without the initial singularity, the big bang), specially the cyclic models, and the Nietzsche's thought of the eternal recurrence. Moreover, we have pointed out reasons for the Nietzsche's search for scientific proofs about the eternal recurrence in the decade of 1880's.

  18. Recurrent aphthous stomatitis

    L Preeti


    Full Text Available Recurrent aphthous ulcers are common painful mucosal conditions affecting the oral cavity. Despite their high prevalence, etiopathogenesis remains unclear. This review article summarizes the clinical presentation, diagnostic criteria, and recent trends in the management of recurrent apthous stomatitis.

  19. Acute recurrent polyhydramnios

    Rode, Line; Bundgaard, Anne; Skibsted, Lillian


    Acute recurrent polyhydramnios is a rare occurrence characterized by a poor fetal outcome. This is a case report describing a 34-year-old woman presenting with acute recurrent polyhydramnios. Treatment with non-steroidal anti-inflammatory drugs (NSAID) and therapeutic amniocenteses was initiated ...

  20. HIV-associated opportunistic CNS infections: pathophysiology, diagnosis and treatment.

    Bowen, Lauren N; Smith, Bryan; Reich, Daniel; Quezado, Martha; Nath, Avindra


    Nearly 30 years after the advent of antiretroviral therapy (ART), CNS opportunistic infections remain a major cause of morbidity and mortality in HIV-positive individuals. Unknown HIV-positive disease status, antiretroviral drug resistance, poor drug compliance, and recreational drug abuse are factors that continue to influence the morbidity and mortality of infections. The clinical and radiographic pattern of CNS opportunistic infections is unique in the setting of HIV infection: opportunistic infections in HIV-positive patients often have characteristic clinical and radiological presentations that can differ from the presentation of opportunistic infections in immunocompetent patients and are often sufficient to establish the diagnosis. ART in the setting of these opportunistic infections can lead to a paradoxical worsening caused by an immune reconstitution inflammatory syndrome (IRIS). In this Review, we discuss several of the most common CNS opportunistic infections: cerebral toxoplasmosis, progressive multifocal leukoencephalopathy (PML), tuberculous meningitis, cryptococcal meningitis and cytomegalovirus infection, with an emphasis on clinical pearls, pathological findings, MRI findings and treatment. Moreover, we discuss the risk factors, pathophysiology and management of IRIS. We also summarize the challenges that remain in management of CNS opportunistic infections, which includes the lack of phase II and III clinical trials, absence of antimicrobials for infections such as PML, and controversy regarding the use of corticosteroids for treatment of IRIS.

  1. Diagnostic and therapeutic challenges in superficial CNS siderosis

    Kondziella, Daniel; Lindelof, M.; Haziri, Donika


    that neurodegeneration due to haemosiderin-associated iron toxicity becomes irreversible with time. CONCLUSION: Surgical therapy in superficial CNS siderosis is rarely achieved. We suggest that prospective, large-scale multicentre studies are needed to search for non-surgical therapies that reverse (or prevent) ongoing...... neurotoxicity due to accumulating iron toxicity. FUNDING: not relevant. TRIAL REGISTRATION: not relevant....


    Nanometer size particles carry free radical activity on their surface and can create oxidative stress (OS)-mediated inflammatory changes upon impact. The oxidative burst signals the activation of phage-lineage cells such as peripheral macrophages, Kupffer cells and CNS microgl...

  3. Detection of CNS and PrPSc in meat products.

    Lücker, Ernst; Hardt, Michael; Groschup, Martin H


    Several methods for the detection of tissues of the central nervous system (CNS) in meat products have been developed and partly validated for use in official food control as pertaining to human BSE-exposure risk. So far, however, methods for the detection of abnormal prion protein (PrPSc) were not evaluated for their potential applicability to the matrix of heat treated meat products. We developed a micro technological procedure for the preparation of meat products suitable for high security laboratories as masses were 6 to 8 orders of magnitude lower than in conventional meat technology. Thus it was possible to produce standard micro sausages containing defined amounts of bovine BSE-positive brain. This material showed all characteristics of normal meat products and a homogeneous distribution of brain as indicated by NSE and GFAP western immunoblotting and GFAP immunometric analyses. Using a commercially available and certified immunometric assay for detection of PrPSc in untreated brain it was possible to detect BSE-positive CNS down to a content of 0.25% in heat treated meat products. We found a high correlation between PrPSc OD-values and CNS content and linearity up to 10% CNS. In 30 samples of retail meat products no sample transgressed the official cut off value for untreated bovine brain. Further studies are needed to show whether an increase of sensitivity in PrPSc detection from the meat product matrix is possible, in particular by optimisation of the extraction procedure.

  4. Causes of CNS inflammation and potential targets for anticonvulsants.

    Falip, Mercé; Salas-Puig, Xavier; Cara, Carlos


    Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.

  5. Commentary on Special Issue : CNS Diseases and the Immune System

    't Hart, Bert A.; den Dunnen, Wilfred F.


    In an increasing number of central nervous system (CNS) diseases a pathogenic contribution of the immune system is proposed. However, the exact underlying mechanisms are often poorly understood. The collection of articles in this special issue presents a state-of-the-art review of adaptive and innat

  6. Communicating the financial worth of the CNS through the use of fiscal reports.

    Ferraro-McDuffie, A; Chan, J S; Jerome, A M


    To maintain the clinical nurse specialist's (CNS's) leading role within hospital nursing services, routine communication to hospital administration of the impact of the CNS role on the hospital's budget is imperative. The CNS group at Children's Hospital of The King's Daughters implemented a quarterly Fiscal Report to clarify the financial worth of CNS practice. The Fiscal Report presents cost savings and revenue generating activities utilizing the role components of the CNS. During fiscal year 1991, the CNS group reported a total impact of $1,600,000. This article describes in detail the use of the Fiscal Report.

  7. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes.

    Karussis, Dimitrios; Petrou, Panayiota


    A wide variety of inflammatory diseases temporally associated with the administration of various vaccines, has been reported in the literature. A PubMed search from 1979 to 2013 revealed seventy one (71) documented cases. The most commonly reported vaccinations that were associated with CNS demyelinating diseases included influenza (21 cases), human papilloma virus (HPV) (9 cases), hepatitis A or B (8 cases), rabies (5 cases), measles (5 cases), rubella (5 cases), yellow fever (3 cases), anthrax (2 cases),meningococcus (2 cases) and tetanus (2 cases). The vast majority of post-vaccination CNS demyelinating syndromes, are related to influenza vaccination and this could be attributed to the high percentage of the population that received the vaccine during the HI1N1 epidemia from 2009 to 2012. Usually the symptoms of the CNS demyelinating syndrome appear few days following the immunization (mean: 14.2 days) but there are cases where the clinical presentation was delayed (more than 3 weeks or even up to 5 months post-vaccination) (approximately a third of all the reported cases). In terms of the clinical presentation and the affected CNS areas, there is a great diversity among the reported cases of post-vaccination acute demyelinating syndromes. Optic neuritis was the prominent clinical presentation in 38 cases, multifocal disseminated demyelination in 30, myelitis in 24 and encephalitis in 17. Interestingly in a rather high proportion of the patients (and especially following influenza and human papiloma virus vaccination-HPV) the dominant localizations of demyelination were the optic nerves and the myelon, presenting as optic neuritis and myelitis (with or without additional manifestations of ADEM), reminiscent to neuromyelitic optica (or, more generally, the NMO-spectrum of diseases). Seven patients suffered an NMO-like disease following HPV and we had two similar cases in our Center. One patient with post-vaccination ADEM, subsequently developed NMO. Overall, the

  8. Expression of LFA-1/ICAM-1 in CNS lymphomas: possible mechanism for lymphoma homing into the brain.

    Bashir, R; Coakham, H; Hochberg, F


    We examined a possible role for the adhesion molecules LFA-1 and ICAM-1 in localizing central nervous system non-Hodgkin's lymphomas (CNS-NHLs) to the brain. Fresh frozen sections from 12 monoclonal CNS NHLs (11 primary, one secondary) were stained with monoclonal antibodies to LFA-1 alpha chain (CD11a), beta chain (CD18) and, ICAM-1 (CD54). Additional staining made use of rat monoclonal antibodies to the human and mouse high endothelial venule antigens HECA 452 and MECA 79 and mouse ICAM-1. The expression of these same molecules was also studied in mice with severe combined immunodeficiency (SCID) mice, bearing intracranial human lymphoblastoid cells. Eleven of the CNS-NHL tumors expressed LFA-1 alpha (one strongly, one intermediate, nine weakly). Nine of the tumors weakly expressed LFA-1 beta.. Nine of twelve tumors weakly expressed ICAM-1. In six of seven tumors definite blood vessels stained for ICAM-1. Non-tumor brain from two patients and non-tumor cerebral blood vessels showed no staining with CD11a, CD18 or CD54 antibodies. Strong expression of LFA-alpha and LFA-beta as well as ICAM-1 was noted in human lymphoblastoid cells (LCLs)/SCID mouse CNS lymphomas. Tumor blood vessels in these mice stained for mouse ICAM-1. Normal SCID mouse brains showed no staining with CD11a, CD18, CD54 or mouse ICAM-1 antibodies. Human, human/mouse CNS lymphomas, normal human, and mouse brains showed no staining with either HECA 452 or MECA 79.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. PEG minocycline-liposomes ameliorate CNS autoimmune disease.

    Wei Hu

    Full Text Available BACKGROUND: Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS. Minocycline, a potent inhibitor of matrix metalloproteinase (MMP-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG minocycline liposomes are effective in treating EAE. FINDINGS: Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs, we determined that PEG minocycline-liposome preparations stabilized with CaCl(2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number. CONCLUSIONS: Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS.

  10. A comprehensive profile of recurrent glioblastoma

    Campos, B.; Olsen, Lars Rønn; Urup, T.


    In spite of relentless efforts to devise new treatment strategies, primary glioblastomas invariably recur as aggressive, therapy-resistant relapses and patients rapidly succumb to these tumors. Many therapeutic agents are first tested in clinical trials involving recurrent glioblastomas. Remarkab...... 2016; doi:10.1038/onc.2016.85....

  11. Long-term recurrence and chronic pain after repair for small umbilical or epigastric hernias

    Christoffersen, Mette W; Helgstrand, Frederik; Rosenberg, Jacob;


    and risk of chronic pain in small primary ventral hernias. METHODS: A cohort study with questionnaire and clinical follow-up was conducted. Patients with primary, elective, open mesh or sutured repair for a small umbilical or epigastric hernia (≤ 2 cm) were included. RESULTS: One thousand three hundred......BACKGROUND: Mesh repair reduces the risk of reoperation for recurrence in patients with primary ventral hernias. However, reoperation for recurrence underestimates total recurrence (reoperation + clinical) and mesh reinforcement may induce chronic pain. This study investigated the total recurrence......-term risk of recurrence after repair for small ventral hernias without increased risk of chronic pain....

  12. AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders

    Ivachtchenko, Alexandre V.; Lavrovsky, Yan; Okun, Ilya


    Lack of efficacy of many new highly selective and specific drug candidates in treating diseases with poorly understood or complex etiology, as are many of central nervous system (CNS) diseases, encouraged an idea of developing multi-modal (multi-targeted) drugs. In this manuscript, we describe molecular pharmacology, in vitro ADME, pharmacokinetics in animals and humans (part of the Phase I clinical studies), bio-distribution, bioavailability, in vivo efficacy, and safety profile of the multimodal drug candidate, AVN-101. We have carried out development of a next generation drug candidate with a multi-targeted mechanism of action, to treat CNS disorders. AVN-101 is a very potent 5-HT7 receptor antagonist (Ki = 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (Ki = 1.2–2.0 nM). AVN-101 also exhibits a rather high affinity toward histamine H1 (Ki = 0.58 nM) and adrenergic α2A, α2B, and α2C (Ki = 0.41–3.6 nM) receptors. AVN-101 shows a good oral bioavailability and facilitated brain-blood barrier permeability, low toxicity, and reasonable efficacy in animal models of CNS diseases. The Phase I clinical study indicates the AVN-101 to be well tolerated when taken orally at doses of up to 20 mg daily. It does not dramatically influence plasma and urine biochemistry, nor does it prolong QT ECG interval, thus indicating low safety concerns. The primary therapeutic area for AVN-101 to be tested in clinical trials would be Alzheimer’s disease. However, due to its anxiolytic and anti-depressive activities, there is a strong rational for it to also be studied in such diseases as general anxiety disorders, depression, schizophrenia, and multiple sclerosis. PMID:27232215

  13. Defining Therapy for Recurrent Platinum-sensitive Ovarian Cancer

    In this phase III clinical trial, women with platinum-sensitive, recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer will be randomly assigned to undergo secondary cytoreductive surgery, if they are candidates for such surgery, and

  14. Primary osteosarcoma of breast

    Gull, Sadaf; Patil, Prashant; Spence, Roy AJ


    Primary osteosarcoma of breast is rare. The authors present a case of a 51-year-old female who was admitted with a large necrotising tumour involving the right breast. CT scan confirmed chest wall invasion along with a solitary lung metastasis. She underwent a primary mastectomy with chest wall reconstruction. Unfortunately 3 months later she developed local recurrence. PMID:22688473

  15. The shifting landscape of metastatic breast cancer to the CNS.

    Quigley, Matthew R; Fukui, Olivia; Chew, Brandon; Bhatia, Sanjay; Karlovits, Steven


    The improved survival following the diagnosis of breast cancer has potentially altered the characteristics and course of patients presenting with CNS involvement. We therefore sought to define our current cohort of breast cancer patients with metastatic disease to the CNS in regard to modern biomarkers and clinical outcome. Review of clinical and radiographic records of women presenting to a tertiary medical center with the new diagnosis of CNS metastatic disease from breast cancer. This was a retrospective review from patients identities obtained from two prospective databases. There were 88 women analyzed who were treated over the period of January 2003 to February 2010, average age 56.9 years. At the time of initial presentation of CNS disease, 68 % of patients had multiple brain metastases, 17 % had a solitary metastasis, and 15 % had only leptomeningeal disease (LMD). The median survival for all patients from the time of diagnosis of breast disease was 50.0 months, and 9.7 months from diagnosis of CNS involvement. The only factor related to overall survival was estrogen receptor-positive pathology (57.6 v. 38.2 months, p = .02 log-rank); those related to survival post CNS diagnosis were presentation with LMD (p = .004, HR = 3.1, Cox regression) and triple-negative hormonal/HER2 status (p = .02, HR = 2.3, Cox regression). Patients with either had a median survival of 3.1 months (no patients in common). Of the 75 patients who initially presented with metastatic brain lesions, 20 (26 %) subsequently developed LMD in the course of their disease (median 10.4 months), following which survival was grim (1.8 months median). Symptoms of LMD were most commonly lower extremity weakness (14/33), followed by cranial nerve deficits (11/33). The recently described Graded Prognostic Assessment (GPA) tumor index stratified median survival at 2.5, 5.9, 13.1, and 21.7 months, respectively, for indices of 1-4 (p = .004, log-rank), which

  16. Differentiation of radiation necrosis from glioblastoma recurrence after radiotherapy

    Chrissa Sioka; Anastasia Zikou; Anna Goussia; Spyridon Tsiouris; Loucas G Astrakas; Athanassios P Kyritsis


    The standard treatment of glioblastoma, the most common type of primary-brain-tumor, involves radiotherapy with concomitant temozolomide chemotherapy. A patient with glioblastoma, post radiotherapy developed magnatic resonance imaging (MRI) changes consistent with either radiation-induced tumor necrosis or tumor recurrence. Perfusion MRI was suggestive of radiation necrosis, but magnetic resonance spectroscopy and99mTc-Tetrofosmin single photon emission computed tomography was indicative of tumor recurrence. Positron emission tomography scan was not available. Tumor recurrence was documented by biopsy. Several advanced imaging methods are available to differentiate tumor recurrence from radiation necrosis in glioblastoma patients. However, in inconclusive cases, brain biopsy should be performed for deifnite diagnosis.

  17. 复发性与初发性肝细胞肝癌实时超声造影比较研究%Comparison of enhancement features of primary hepatocellular carcinoma and recurrent hepatocelluar carcinoma on contrast-enhanced ultrasonography

    魏瑞雪; 王文平; 丁红; 黄备建; 李超伦; 韩红; 季正标


    目的 比较复发性与初发性肝细胞肝癌实时超声造影时相特征.方法 对初发性肝细胞肝癌患者83例(93个肿瘤)和复发性肝细胞肝癌患者56例(70个肿瘤)进行实时灰阶谐波超声造影,比较初发性肿瘤与复发性肿瘤的造影增强时相变化.结果 从注射造影剂开始到肿块回声较肝实质低的时间,复发性与初发性肝细胞肝癌组分别为(104.0±51.8)s和(85.5±43.0)s,两组间差别有显著统计学意义(P=0.010).复发性和初发性肝癌在门脉期中表现为等回声的比例分别为34.3%(24/70),17.2%(16/93),前者明显高于后者(P=0.012).结论 复发性肝细胞肝癌与初发性肝细胞肝癌超声造影表现有一定差异,认识这一规律将有助于复发性肝细胞肝癌的早期诊断.%Objective To compare enhancement features of primary hepatocellular carcinoma(PHCC)and recurrent hepatocellular carcinoma(RHCC) on.contrast-enhanced ultrasonography(CEUS). Methods CEUS was performed in 56 patients with 70 RHCC and 83 patients with 93 PHCC. The enhancement features of these two groups of hepatocellular carcinoma were compared. The time used for the enhancement material to arrive the lesion(Ta ), that used for the lesion to become isoechoic(T1 ) and hypoechoic relative to the surrounding hepatic parenchyma(To) were analyzed. The echogenicity change between the lesion and the parenchyma was observed during arterial phase,portal phase and delayed phase. Results The time used for the lesion to become hypoechogenicity of RHCC and PHCC was (104.0 ± 51.8)s, (85.5 ± 43.0)srespectively,there was significant difference between the two groups( P = 0.010). There were 24 (34.3 % )cases of RHCC and 16 ( 17.2% ) cases of PHCC becoming isoechoic during portal phase,the former rate was significantly higher than the later one( P = 0. 012). Conclusions There is significant difference between PHCC and RHCC in the performance of CEUS,this is useful for the early diagnosis of RHCC.

  18. Identification of CNS neural circuitry involved in the innervation of C7 spinal nerve: a viral transsynaptic tracing study

    WEI Hai-feng; CHEN Liang; GU Yu-dong


    Objective: Contralateral C7 spinal nerve transfer is a useful operation for the treatment of brachial plexus root avulsion. The recovery of the independent function at the ipsilateral side, however, depends on neural circuitry reorganization in the central nervous system (CNS).This study tried to locate the CNS neuronal elements involved in the innervation ofC7 spinal nerve.Method: Pseudorabies virus (PRV, TK/gG-,2 μl), which expressed green fluorescent protein (GFP), was injected into the left C7 spinal nerve in 20 adult Sprague Dawley rats.After rats survived for 6 h, 12 h, 24 h and 36 h, the C1-C7segments of the spinal cord and brain were processed using a polyclonal immunohistochemical antibody against PRV.Results: PRV-labeled neurons were found mainly in gray matter of the C1-C7 segments of the spinal cord and at the following structures of the brain: lateral vestibular nucleus, lateral paragigantocellular nucleus, A5 cells, red nucleus, primary and secondary motor cortexes, primary and secondary somatosensory cortexes. Although located bilaterally, the PRV-labeled neurons existed predominantly in the ipsilateral side of the spinal cord and the contralateral side of the brain at 6-12 h after injection (p.i.). The number of PRV-labeled neurons in the CNS was increasing with rat's survival time and the distribution of these neurons turned bilateral with no obvious dominance to either side at 24 h and 36 h (p.i.).Conclusion: By use of transsynaptic tracing technique with PRV, the anatomically connected set of neurons,which modulates the activity of C7 spinal nerve, is located successfully in the CNS.

  19. Identification of CNS neural circuitry involved in the innervation of C7 spinal nerve: a viral transsynaptic tracing study

    WEI Hai-feng


    Full Text Available 【Abstract】 Objective: Contralateral C7 spinal nerve transfer is a useful operation for the treatment of brachial plexus root avulsion. The recovery of the independent function at the ipsilateral side, however, depends on neural circuitry reorganization in the central nervous system (CNS. This study tried to locate the CNS neuronal elements involved in the innervation of C7 spinal nerve. Method: Pseudorabies virus (PRV, TK/gG-, 2 祃, which expressed green fluorescent protein (GFP, was injected into the left C7 spinal nerve in 20 adult Sprague Dawley rats. After rats survived for 6 h, 12 h, 24 h and 36 h, the C1-C7 segments of the spinal cord and brain were processed using a polyclonal immunohistochemical antibody against PRV. Results: PRV-labeled neurons were found mainly in gray matter of the C1-C7 segments of the spinal cord and at the following structures of the brain: lateral vestibular nucleus, lateral paragigantocellular nucleus, A5 cells, red nucleus, primary and secondary motor cortexes, primary and secondary somatosensory cortexes. Although located bilaterally, the PRV-labeled neurons existed predominantly in the ipsilateral side of the spinal cord and the contralateral side of the brain at 6-12 h after injection (p.i.. The number of PRV-labeled neurons in the CNS was increasing with rat抯 survival time and the distribution of these neurons turned bilateral with no obvious dominance to either side at 24 h and 36 h (p.i.. Conclusion: By use of transsynaptic tracing technique with PRV, the anatomically connected set of neurons, which modulates the activity of C7 spinal nerve, is located successfully in the CNS. Key words: Brachial plexus; Innervation; Spinal nerves; Central nervous system

  20. Recurrent Breast Cancer

    ... that can help you cope with distress include: Art therapy Dance or movement therapy Exercise Meditation Music ... . Mayo Clinic Footer Legal Conditions and ...

  1. Mycobacterium tuberculosis-infected human monocytes down-regulate microglial MMP-2 secretion in CNS tuberculosis via TNFα, NFκB, p38 and caspase 8 dependent pathways

    Elkington Paul T


    Full Text Available Abstract Tuberculosis (TB of the central nervous system (CNS is a deadly disease characterized by extensive tissue destruction, driven by molecules such as Matrix Metalloproteinase-2 (MMP-2 which targets CNS-specific substrates. In a simplified cellular model of CNS TB, we demonstrated that conditioned medium from Mycobacterium tuberculosis-infected primary human monocytes (CoMTb, but not direct infection, unexpectedly down-regulates constitutive microglial MMP-2 gene expression and secretion by 72.8% at 24 hours, sustained up to 96 hours (P M.tb-infected monocyte-dependent networks paradoxically involves the pro-inflammatory mediators TNF-α, p38 MAP kinase and NFκB in addition to a novel caspase 8-dependent pathway.

  2. Multifocal recurrent periostitis

    Kozlowski, K.; Anderson, R.; Tink, A.


    Two case reports of recurrent multifocal periostitis in two girls aged 15 and 16 are added to the eight cases already reported in the literature. The disease is characterised clinically by recurrent mesomelic swelling of the extremities and radiologically by periosteal thickening and sclerosis of underlying bone. Hyperglobulinaemia is the most constant biochemical finding. The bone biopsy shows no typical features. The possibility of a viral etiology is discussed.

  3. Recurrences of strange attractors

    E J Ngamga; A Nandi; R Ramaswamy; M C Romano; M Thiel; J Kurths


    The transitions from or to strange nonchaotic attractors are investigated by recurrence plot-based methods. The techniques used here take into account the recurrence times and the fact that trajectories on strange nonchaotic attractors (SNAs) synchronize. The performance of these techniques is shown for the Heagy-Hammel transition to SNAs and for the fractalization transition to SNAs for which other usual nonlinear analysis tools are not successful.

  4. CNS metastasis from malignant uveal melanoma: a clinical and histopathological characterisation

    Holfort, S K; Lindegaard, J; Isager, P;


    to the CNS were identified. For each patient, clinical and histopathological data were gathered. RESULTS: Sixteen patients with CNS metastasis were identified. The median age was 58 years. The majority of CNS metastases were located in the frontal and parietal lobes. Eleven patients had widespread metastases...

  5. Cancer immunology and colorectal cancer recurrence.

    Vannucci, Luca


    The recurrence of a cancer - local or distant (metastasis) - is manifested by the persistence of cancer cells in the organism after the ablation of the primary lesion, an ineffective anticancer immune response, and by the activity of biological/immunological factors that can stimulate and sustain its development. This review focuses on colorectal carcinoma and discusses some aspects of cancer immunology regarding cancer development and its recurrence. It is addressed also to the clinician to provide new insights helpful for designing better therapeutic strategies and patient's follow up. Therapeutic approaches used during and after surgical treatments, found capable of modulating immunity (differently affecting disease outcome), will also be described.

  6. Pulsar/CNS integrated navigation based on federated UKF

    Jin Liu; Jie Ma; Jinwen Tian


    In order to improve the autonomous navigation capability of satellite,a pulsar/CNS(celestial navigation system)integrated navigation method based on federated unscented Kalman filter(UKF)is proposed.The celestial navigation is a mature and stable navigation method.However,its position determination performance is not satisfied due to the low accuracy of horizon sensor.Single pulsar navigation is a new navigation method,which can provide highly accurate range measurements.The major drawback of single pulsar navigation is that the system is completely unobservabie.As two methods are complementary to each other,the federated UKF is used here for fusing the navigation data from single pulsar navigation and CNS.Compared to the traditional celestial navigation method and single pulsar navigation,the integrated navigation method can provide better navigation performance.The simulation results demonstrate the feasibility and effectiveness of the navigation method.

  7. Positron emission tomography in CNS drug discovery and drug monitoring.

    Piel, Markus; Vernaleken, Ingo; Rösch, Frank


    Molecular imaging methods such as positron emission tomography (PET) are increasingly involved in the development of new drugs. Using radioactive tracers as imaging probes, PET allows the determination of the pharmacokinetic and pharmacodynamic properties of a drug candidate, via recording target engagement, the pattern of distribution, and metabolism. Because of the noninvasive nature and quantitative end point obtainable by molecular imaging, it seems inherently suited for the examination of a pharmaceutical's behavior in the brain. Molecular imaging, most especially PET, can therefore be a valuable tool in CNS drug research. In this Perspective, we present the basic principles of PET, the importance of appropriate tracer selection, the impact of improved radiopharmaceutical chemistry in radiotracer development, and the different roles that PET can fulfill in CNS drug research.

  8. Autoradiographic visualization of CNS receptors for vasoactive intestinal peptide

    Shaffer, M.M.; Moody, T.W.


    Receptors for VIP were characterized in the rat CNS. /sup 125/I-VIP bound with high affinity to rat brain slices. Binding was time dependent and specific. Pharmacology studies indicated that specific /sup 125/I-VIP binding was inhibited with high affinity by VIP and low affinity by secretin and PHI. Using in vitro autoradiographic techniques high grain densities were present in the dentate gyrus, pineal gland, supraoptic and suprachiasmatic nuclei, superficial gray layer of the superior colliculus and the area postrema. Moderate grain densities were present in the olfactory bulb and tubercle, cerebral cortex, nucleus accumbens, caudate putamen, interstitial nucleus of the stria terminalis, paraventricular thalamic nucleus, medial amygdaloid nucleus, subiculum and the medial geniculate nucleus. Grains were absent in the corpus callosum and controls treated with 1 microM unlabeled VIP. The discrete regional distribution of VIP receptors suggest that it may function as an important modulator of neural activity in the CNS.

  9. Re-recurrence after operation for recurrent inguinal hernia. A nationwide 8-year follow-up study on the role of type of repair

    Bisgaard, Thue; Bay-Nielsen, M.; Kehlet, H.


    OBJECTIVES: We analyze, on a nationwide basis, the risk of re-reoperation with reference to previous inguinal hernia repair technique. SUMMARY BACKGROUND DATA: Operation for a recurrent inguinal hernia is common and the risk of re-recurrence is high. There are no large-scale data evaluating...... the surgical strategy and results after recurrent inguinal hernia repairs. METHODS: Prospective recording of all primary and subsequent recurrent inguinal hernia repairs from January 1, 1998 to December 31, 2005, in the national Danish Hernia Database, using the reoperation rate as a proxy for recurrence....... The re-reoperation rate was analyzed with reference to the technique of primary and recurrent inguinal hernia repair. RESULTS: After 67,306 primary hernia repairs there were 2117 reoperations (3.1%) and 187 re-reoperations (8.8%). The cumulated re-reoperation rate after primary Lichtenstein repair (n...


    F. Jadali


    Full Text Available AbstractObjectiveTumors of the central nervous system constitute the largest group of solid neoplasms in children and are second only to leukemia in their overall frequency during childhood. The main purpose of the present study is to determine the incidence, age, sex, location and histological diagnosis of CNS tumors in children, less than 15 years of age, in the Mofid Children's Hospital, in the past 10 years. Materials and MethodsIn this descriptive retrospective study we reviewed the medical records of 143 children with diagnosis of CNS tumors admitted during the past 10 years in neurology and surgery departments of Mofid Children's Hospital between the years 1996 and 2006.ResultsDuring the 10 year study period, CNS tumor was diagnosed in 143 patients; of these tumors, 119 were intracranial and 58 were intraspinal; 51.3% of brain tumors were located in the supratentorial and 48.7% in the infratentorial regions. The most common intracranial neoplasms were astrocytic tumors (36.8%, embryonal tumors (31.1% and ependymal tumors (13.4%. Of the intraspinal neoplasms the most frequently noted were embryonal tumors(37.5%, mesenchymal meningothelial tumors (20.8%, followed by astrocytic tumors (16.7%. The median age at diagnosis was 8.9 ± 4.1 years with a male to female ratio of 1.4:1 (P Conclusion Brain tumors in children constitute a diverse group in terms of incidence,distribution and histopathological diagnosis.Keywords: CNS tumors, Histopathology, Children.

  11. 4th ENRI International Workshop on ATM/CNS


    This book is a compilation of selected papers from the 4th ENRI International Workshop on ATM/CNS (EIWAC2015). The work focuses on novel techniques for aviation infrastructure in air traffic management (ATM) and communications, navigation, surveillance, and informatics (CNSI) domains. The contents make valuable contributions to academic researchers, engineers in the industry, and regulators of aviation authorities. As well, readers will encounter new ideas for realizing a more efficient and safer aviation system. .

  12. Virally mediated gene manipulation in the adult CNS

    Efrat eEdry


    Full Text Available Understanding how the CNS functions poses one of the greatest challenges in modern life science and medicine. Studying the brain is especially challenging because of its complexity, the heterogeneity of its cellular composition, and the substantial changes it undergoes throughout its life-span. The complexity of adult-brain neural networks results also from the diversity of properties and functions of neuronal cells, governed, inter alia, by temporally and spatially differential expression of proteins in mammalian brain cell populations. Hence, research into the biology of CNS activity and its implications to human and animal behavior must use novel scientific tools. One source of such tools is the field of molecular genetics – recently utilized more and more frequently in neuroscience research. Transgenic approaches in general, and gene targeting in rodents have become fundamental tools for elucidating gene function in the CNS. Although spectacular progress has been achieved over recent decades by using these approaches, it is important to note that they face a number of restrictions. One of the main challenges is presented by the temporal and spatial regulation of introduced genetic manipulations. Viral vectors provide an alternative approach to temporally regulated, localized delivery of genetic modifications into neurons. In this review we describe available technologies for gene transfer into the adult mammalian CNS that use both viral and non-viral tools. We discuss viral vectors frequently used in neuroscience, with emphasis on lentiviral vector (LV systems. We consider adverse effects of LVs, and the use of LVs for temporally and spatially controllable manipulations. Especially, we highlight the significance of viral vector-mediated genetic manipulations in studying learning and memory processes, and how they may be effectively used to separate out the various phases of learning: acquisition, consolidation, retrieval, and maintenance.

  13. Myelin Damage and Repair in Pathologic CNS: Challenges and Prospects

    Arsalan eAlizadeh


    Full Text Available Injury to the central nervous system (CNS results in oligodendrocyte cell death and progressive demyelination. Demyelinated axons undergo considerable physiological changes and molecular reorganizations that collectively result in axonal dysfunction, degeneration and loss of sensory and motor functions. Endogenous adult oligodendrocyte precursor cells (OPCs and neural stem/progenitor cells (NPCs contribute to the replacement of oligodendrocytes, however, the extent and quality of endogenous remyelination is suboptimal. Emerging evidence indicates that optimal remyelination is restricted by multiple factors including (i low levels of factors that promote oligodendrogenesis; (ii cell death among newly generated oligodendrocytes, (iii inhibitory factors in the post-injury milieu that impede remyelination, and (iv deficient expression of key growth factors essential for proper re-construction of a highly organized myelin sheath. Considering these challenges, over the past several years, a number of cell-based strategies have been developed to optimize remyelination therapeutically. Outcomes of these basic and preclinical discoveries are promising and signify the importance of remyelination as a mechanism for improving functions in CNS injuries. In this review, we provide an overview on: 1 the precise organization of myelinated axons and the reciprocal axo-myelin interactions that warrant properly balanced physiological activities within the CNS; 2 underlying cause of demyelination and the structural and functional consequences of demyelination in axons following injury and disease; 3 the endogenous mechanisms of oligodendrocyte replacement; 4 the modulatory role of reactive astrocytes and inflammatory cells in remyelination; and 5 the current status of cell-based therapies for promoting remyelination. Careful elucidation of the cellular and molecular mechanisms of demyelination in the pathologic CNS is a key to better understanding the impact of

  14. Target Identification for CNS Diseases by Transcriptional Profiling

    Altar, C. Anthony; Vawter, Marquis P.; Ginsberg, Stephen D.


    Gene expression changes in neuropsychiatric and neurodegenerative disorders, and gene responses to therapeutic drugs, provide new ways to identify central nervous system (CNS) targets for drug discovery. This review summarizes gene and pathway targets replicated in expression profiling of human postmortem brain, animal models, and cell culture studies. Analysis of isolated human neurons implicates targets for Alzheimer’s disease and the cognitive decline associated with normal aging and mild ...

  15. Leptin and the CNS Control of Glucose Metabolism

    Morton, Gregory J.; Schwartz, Michael W.


    The regulation of body fat stores and blood glucose levels is critical for survival. This review highlights growing evidence that leptin action in the central nervous system (CNS) plays a key role in both processes. Investigation into underlying mechanisms has begun to clarify the physiological role of leptin in the control of glucose metabolism and raises interesting new possibilities for the treatment of diabetes and related disorders. PMID:21527729

  16. Rickettsioses as causes of CNS infection in southeast Asia

    Carole Eldin; Philippe Parola


    International audience; In The Lancet Global Health, Sabine Dittrich and colleagues 1 report that scrub typhus caused by Orientia tsutsugamushi, murine typhus caused by Rickettsia typhi, and leptospirosis caused by various Leptospira species account for more than a third of CNS infections diagnosed over 8 years in Vientiane Hospital in Laos. The study is one more great contribution from this team in their investigation of undocumented syndromes, as well as in the public health challenge of ri...

  17. Surgical treatment of intra hepatic recurrence ofhepatocellular carcinoma


    Recurrence after hepatocellular carcinoma (HCC) isfrequent. Currently, there are no recommendations ontherapeutic strategy after recurrence of HCC. Whereasthe 5 year-recurrence rate after resection of HCC is 100%,this drops to 15% after primary liver transplantation.Repeat hepatectomy and salvage liver transplantation(SLT) could be performed in selected patients to treatrecurrent HCC and enable prolonged overall survivalafter treatment of recurrence. Other therapies such aslocal ablation, chemoembolization or sorafenib couldbe proposed to those patients unable to benefit fromresection or SLT. A clear definition of the place of SLT and"prophylactic" liver transplantation is required. Indeed,identifying risks factors for recurrence at time of primaryliver resection of HCC may help to avoid recurrencebeyond Milan criteria and non-resectable situations. Inthis review, we summarize the recent data available inthe literature on the feasibility and outcomes of repeathepatectomy and SLT as treatment for recurrent HCC.

  18. Mechanisms of CNS invasion and damage by parasites.

    Kristensson, Krister; Masocha, Willias; Bentivoglio, Marina


    Invasion of the central nervous system (CNS) is a most devastating complication of a parasitic infection. Several physical and immunological barriers provide obstacles to such an invasion. In this broad overview focus is given to the physical barriers to neuroinvasion of parasites provided at the portal of entry of the parasites, i.e., the skin and epithelial cells of the gastrointestinal tract, and between the blood and the brain parenchyma, i.e., the blood-brain barrier (BBB). A description is given on how human pathogenic parasites can reach the CNS via the bloodstream either as free-living or extracellular parasites, by embolization of eggs, or within red or white blood cells when adapted to intracellular life. Molecular mechanisms are discussed by which parasites can interact with or pass across the BBB. The possible targeting of the circumventricular organs by parasites, as well as the parasites' direct entry to the brain from the nasal cavity through the olfactory nerve pathway, is also highlighted. Finally, examples are given which illustrate different mechanisms by which parasites can cause dysfunction or damage in the CNS related to toxic effects of parasite-derived molecules or to immune responses to the infection.

  19. Origin, fate and dynamics of macrophages at CNS interfaces

    Goldmann, Tobias; Jordão, Marta Joana Costa; Wieghofer, Peter; Prutek, Fabiola; Hagemeyer, Nora; Frenzel, Kathrin; Staszewski, Ori; Kierdorf, Katrin; Amann, Lukas; Krueger, Martin; Locatelli, Giuseppe; Hochgarner, Hannah; Zeiser, Robert; Epelman, Slava; Geissmann, Frederic; Priller, Josef; Rossi, Fabio; Bechmann, Ingo; Kerschensteiner, Martin; Linnarsson, Sten; Jung, Steffen; Prinz, Marco


    Perivascular, meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It has been assumed that they have a high turnover with blood-borne monocytes. However, large scale single-cell RNA-sequencing reveals a striking molecular overlap between perivascular macrophages and microglia but not monocytes. Using several fate mapping approaches and parabiosis we demonstrate that CNS macrophages arise from yolk sac precursors during embryonic development and remain a stable population. Notably, the generation of CNS macrophages relies on the transcription factor Pu.1 whereas myb, Batf3 and Nr4a1 are not required. Upon autoimmune inflammation, macrophages undergo extensive self-renewal by local proliferation. Our data provide challenging new insights into brains innate immune system. PMID:27135602

  20. PPAR agonists as therapeutics for CNS trauma and neurological diseases

    Mandrekar-Colucci, Shweta; Sauerbeck, Andrew; Popovich, Phillip G.; McTigue, Dana M.


    Traumatic injury or disease of the spinal cord and brain elicits multiple cellular and biochemical reactions that together cause or are associated with neuropathology. Specifically, injury or disease elicits acute infiltration and activation of immune cells, death of neurons and glia, mitochondrial dysfunction, and the secretion of substrates that inhibit axon regeneration. In some diseases, inflammation is chronic or non-resolving. Ligands that target PPARs (peroxisome proliferator-activated receptors), a group of ligand-activated transcription factors, are promising therapeutics for neurologic disease and CNS injury because their activation affects many, if not all, of these interrelated pathologic mechanisms. PPAR activation can simultaneously weaken or reprogram the immune response, stimulate metabolic and mitochondrial function, promote axon growth and induce progenitor cells to differentiate into myelinating oligodendrocytes. PPAR activation has beneficial effects in many pre-clinical models of neurodegenerative diseases and CNS injury; however, the mechanisms through which PPARs exert these effects have yet to be fully elucidated. In this review we discuss current literature supporting the role of PPAR activation as a therapeutic target for treating traumatic injury and degenerative diseases of the CNS. PMID:24215544

  1. Paclitaxel and Carboplatin in Treating Patients With Metastatic or Recurrent Solid Tumors and HIV Infection


    HIV Infection; Recurrent Anal Cancer; Recurrent Breast Cancer; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Anal Cancer; Stage IV Breast Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Unspecified Adult Solid Tumor, Protocol Specific

  2. Clinicopathologic factors associated with recurrence in parotid carcinoma.

    Lee, Dong Hoon; Yoon, Tae Mi; Lee, Joon Kyoo; Lim, Sang Chul


    Parotid carcinomas have varying histological types and diverse biologic behaviors. Establishing an adequate treatment plan and predicting recurrence is important. To analyze the risk factors associated with recurrence in our 5 year experience with 30 cases of primary parotid carcinoma undergoing surgery at a single institute. From January 2009 to December 2013, 30 patients with surgical treatment of parotid carcinoma were identified based on their medical records. The 30 patients were comprised of 17 males and 13 females. Among 11 patients with T4 tumors, seven patients had recurrence. Among seven patients with cervical nodal metastasis, all patient except one had recurrence. Clinically late stages (stage III and IV) showed more common recurrence than early stage (stage I and II) lesions. Lymphovascular invasion was seen in 5 patients, and all patients had recurrence. Among 11 patients with extracapsular spread, 7 patients had recurrence. In 17 patients with high grade carcinomas, ten patients had recurrence. In 13 patients with low grade carcinomas, no patients experienced recurrence. T- and N-stage, clinical stage, lymphovascular invasion, extracapsular spread, and histopathologic grade correlate significantly with recurrence in parotid carcinoma. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  3. Primary Angiitis of the Central Nervous System

    Mojdeh Ghabaee


    Full Text Available Primary angiitis of the central nervous system (PACNS is an idiopathic disorder (vasculitis restricted to the central nervous system (CNS. It often presents with focal neurological deficits suggesting stroke or a combination of confusion and headache. We herein report three cases with various combinations of fever, partial seizure, encephalopathy, paresis, headache and ataxia. One of them was initially treated as herpes simplex meningoencephalitis, but further investigations revealed primary angiitis. Primary angiitis of the CNS has protean manifestations and should always be considered in patients suspicious to have CNS infection or stroke, particularly who does not respond to the routine treatments. Clinical data, exclusion of differential diagnoses and typical angiography seem to be enough to justify the diagnosis in the majority of cases.

  4. Surgical approach for recurrent inguinal hernias

    Öberg, S; Andresen, K; Rosenberg, J


    Purpose: Guidelines recommend that the reoperation of a recurrent inguinal hernia should be by the opposite approach (anterior–posterior) than the primary repair. However, the level of evidence supporting the guidelines is partially low. The purpose of this study was to compare re-reoperation rates...... between repairs performed according to the guidelines with the ones performed against it. Methods: This cohort study was based on the Danish Hernia Database, including 4344 patients with two inguinal hernia repairs in the same groin. Four groups were compared as follows: Lichtenstein–Lichtenstein vs......-reoperation for Lichtenstein–Lichtenstein was only seen if the primary hernia was medial. Conclusions: A primary Lichtenstein repair of a primary medial hernia should be reoperated with a laparoscopic repair. A primary Lichtenstein repair of a primary lateral hernia can be reoperated with either a Lichtenstein...

  5. Immune Privilege as an Intrinsic CNS Property: Astrocytes Protect the CNS against T-Cell-Mediated Neuroinflammation

    Ulrike Gimsa


    Full Text Available Astrocytes have many functions in the central nervous system (CNS. They support differentiation and homeostasis of neurons and influence synaptic activity. They are responsible for formation of the blood-brain barrier (BBB and make up the glia limitans. Here, we review their contribution to neuroimmune interactions and in particular to those induced by the invasion of activated T cells. We discuss the mechanisms by which astrocytes regulate pro- and anti-inflammatory aspects of T-cell responses within the CNS. Depending on the microenvironment, they may become potent antigen-presenting cells for T cells and they may contribute to inflammatory processes. They are also able to abrogate or reprogram T-cell responses by inducing apoptosis or secreting inhibitory mediators. We consider apparently contradictory functions of astrocytes in health and disease, particularly in their interaction with lymphocytes, which may either aggravate or suppress neuroinflammation.

  6. Laparoscopic Surgery for Recurrent Crohn's Disease

    Antonino Spinelli


    Full Text Available In spite of the recent improvements in drug therapy, surgery still represents the most frequent treatment for Crohn's disease (CD complications. Laparoscopy has been widely applied over the last twenty years in colorectal surgery and was associated with lower postoperative pain, shorter hospitalization, faster return to daily activities, and better cosmetic results. Laparoscopy experienced a slower diffusion in inflammatory bowel disease surgery than in oncologic colorectal surgery, but proved to be safe and effective, and is currently considered the gold standard for the treatment of primary uncomplicated ileocolic CD. Indications for laparoscopy in CD have recently been widened to embrace more complicated or recurrent CD. This paper reviews the available data on the subset of recurrent CD patients. The reported results indicate that laparoscopy may be safely applied even in selected recurrent CD cases in hands of IBD surgeons with broad laparoscopic experience.

  7. Management of Recurrent Aphthous Stomatitis in Children.

    Montgomery-Cranny, Jodie A; Wallace, Ann; Rogers, Helen J; Hughes, Sophie C; Hegarty, Anne M; Zaitoun, Halla


    Recurrent oral ulceration is common and may present in childhood. Causes of recurrent oral ulceration are numerous and there may be an association with underlying systemic disease. Recurrent aphthous stomatitis (RAS) is the most common underlying diagnosis in children. The discomfort of oral ulcers can impact negatively on quality of life of a child, interfering with eating, speaking and may result in missed school days. The role of the general dental practitioner is to identify patients who can be treated with simple measures in primary dental care and those who require assessment and treatment in secondary care. Management may include topical agents for symptomatic relief, topical corticosteroids and, in severe recalcitrant cases, systemic agents may be necessary.

  8. Recurrent otorrhea in chronic suppurative otitis media

    Jensen, Ramon Gordon; Johansen, Helle Krogh; Bjarnsholt, Thomas


    of otorrhea in CSOM. In a prospective case series at a primary healthcare clinic in Nuuk, Greenland, patients with more than 14 days of otorrhea were included consecutively. Samples for culturing and biofilm analysis were taken at enrollment and at any subsequent episode with otorrhea. Participants were...... treated with daily saline irrigation and Ciprofloxacin eardrops for 7–14 days. Biofilm was identified in otorrhea in 81% (17/21) of participants at enrollment. Multispecies infections dominated with Non-typeable Haemophilus Influenzae (NTHI), Staphyloccocus aureus, and anaerobes being the most frequent...... pathogens. After the initial treatment, 19 (90%) had dry ears. Median observation period was 140 days (range 14–280) where 13 participants had one or more recurrences. Median time to first recurrence was 60 days (range 14–197). Among the 13 with recurrence, three individuals had the same genotype...

  9. Central nervous system involvement in primary Sjögren's syndrome

    Xiao-yu DONG


    Full Text Available Clinical and imaging data of 4 cases of primary Sjögren's syndrome (pSS combined with central nervous system (CNS lesions were retrospectively analyzed. Clinical symptoms of 4 patients were as follows: 2 cases had fever; 2 cases had blurred vision; 2 cases had lower extremity weakness; one case had single lower limb weakness; one case had unilateral limb weakness; one case had hemisensory reduction; one case had bilateral abducens paralysis; 3 cases had peripheral neuropathy. Analysis of cerebrospinal fluid (CSF revealed increased CSF pressure (210-270 mm H2O in 3 cases, increased number of leukocyte [(50-380 × 10 6/L] in 3 cases, and increased protein (1.30-2.56 g/L in 3 cases. Brain MRI showed multiple lesions in white matters. After high-dose steroid therapy, 3 cases had good prognosis, and one had recurrent lower extremity weakness after 6 months. pSS combined with CNS lesions is rare. Lumbar puncture and brain MRI is important for diagnosis, and high-dose steroid therapy may have good therapeutic effect. DOI: 10.3969/j.issn.1672-6731.2015.04.014

  10. Radiotherapy in the treatment of primary central nervous system lymphoma (PCNSL).

    Nelson, D F


    The use of radiotherapy alone to treat primary central nervous system lymphoma (PCNSL) does not produce the high local control and survival rates that it does in limited extranodal non-Hodgkin's lymphoma outside the central nervous system (CNS). Even with doses of whole brain radiation therapy (WBRT) to 40+20 Gy boost, the Radiation Therapy Oncology Group (RTOG) reported a local control rate of 39%. Seventy-nine percent of recurrences were in the 60 Gy region. The median survival was 11.6 months. This response to local radiotherapy is quite different from the response of non-CNS Diffuse Large Cell Lymphoma where doses of 30-40 and >40 Gy have a 75-90% local control rate. Neither systemic lymphoma nor PCNSL have a classic radiotherapy dose response. For PCNSL there appears to be a threshold dose that ranges in the literature between 30 and > 50 Gy with a median of 40 Gy. Therefore, when radiotherapy is combined with chemotherapy that crosses the BBB, WBRT and/or boost doses may be able to be decreased, especially in patients achieving a complete response. Promising data from the Centre Leon Berard suggest that this is possible. When such chemotherapy was combined with intrathecal chemotherapy and 20 Gy WBRT, they obtained a 56% actuarial 5 year survival rate. Confirmation of single institution reports of favorable results such as these are needed. Cooperative group and intergroup trials are needed to define optimal therapy.

  11. Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis.

    Jordan, Sabine D; Könner, A Christine; Brüning, Jens C


    The central nervous system (CNS) is capable of gathering information on the body's nutritional state and it implements appropriate behavioral and metabolic responses to changes in fuel availability. This feedback signaling of peripheral tissues ensures the maintenance of energy homeostasis. The hypothalamus is a primary site of convergence and integration for these nutrient-related feedback signals, which include central and peripheral neuronal inputs as well as hormonal signals. Increasing evidence indicates that glucose and lipids are detected by specialized fuel-sensing neurons that are integrated in these hypothalamic neuronal circuits. The purpose of this review is to outline the current understanding of fuel-sensing mechanisms in the hypothalamus, to integrate the recent findings in this field, and to address the potential role of dysregulation in these pathways in the development of obesity and type 2 diabetes mellitus.

  12. Recurrent Fever in Children.

    Torreggiani, Sofia; Filocamo, Giovanni; Esposito, Susanna


    Children presenting with recurrent fever may represent a diagnostic challenge. After excluding the most common etiologies, which include the consecutive occurrence of independent uncomplicated infections, a wide range of possible causes are considered. This article summarizes infectious and noninfectious causes of recurrent fever in pediatric patients. We highlight that, when investigating recurrent fever, it is important to consider age at onset, family history, duration of febrile episodes, length of interval between episodes, associated symptoms and response to treatment. Additionally, information regarding travel history and exposure to animals is helpful, especially with regard to infections. With the exclusion of repeated independent uncomplicated infections, many infective causes of recurrent fever are relatively rare in Western countries; therefore, clinicians should be attuned to suggestive case history data. It is important to rule out the possibility of an infectious process or a malignancy, in particular, if steroid therapy is being considered. After excluding an infectious or neoplastic etiology, immune-mediated and autoinflammatory diseases should be taken into consideration. Together with case history data, a careful physical exam during and between febrile episodes may give useful clues and guide laboratory investigations. However, despite a thorough evaluation, a recurrent fever may remain unexplained. A watchful follow-up is thus mandatory because new signs and symptoms may appear over time.

  13. Recurrent Fever in Children

    Sofia Torreggiani


    Full Text Available Children presenting with recurrent fever may represent a diagnostic challenge. After excluding the most common etiologies, which include the consecutive occurrence of independent uncomplicated infections, a wide range of possible causes are considered. This article summarizes infectious and noninfectious causes of recurrent fever in pediatric patients. We highlight that, when investigating recurrent fever, it is important to consider age at onset, family history, duration of febrile episodes, length of interval between episodes, associated symptoms and response to treatment. Additionally, information regarding travel history and exposure to animals is helpful, especially with regard to infections. With the exclusion of repeated independent uncomplicated infections, many infective causes of recurrent fever are relatively rare in Western countries; therefore, clinicians should be attuned to suggestive case history data. It is important to rule out the possibility of an infectious process or a malignancy, in particular, if steroid therapy is being considered. After excluding an infectious or neoplastic etiology, immune-mediated and autoinflammatory diseases should be taken into consideration. Together with case history data, a careful physical exam during and between febrile episodes may give useful clues and guide laboratory investigations. However, despite a thorough evaluation, a recurrent fever may remain unexplained. A watchful follow-up is thus mandatory because new signs and symptoms may appear over time.

  14. The farnesoid-X-receptor in myeloid cells controls CNS autoimmunity in an IL-10-dependent fashion.

    Hucke, Stephanie; Herold, Martin; Liebmann, Marie; Freise, Nicole; Lindner, Maren; Fleck, Ann-Katrin; Zenker, Stefanie; Thiebes, Stephanie; Fernandez-Orth, Juncal; Buck, Dorothea; Luessi, Felix; Meuth, Sven G; Zipp, Frauke; Hemmer, Bernhard; Engel, Daniel Robert; Roth, Johannes; Kuhlmann, Tanja; Wiendl, Heinz; Klotz, Luisa


    Innate immune responses by myeloid cells decisively contribute to perpetuation of central nervous system (CNS) autoimmunity and their pharmacologic modulation represents a promising strategy to prevent disease progression in Multiple Sclerosis (MS). Based on our observation that peripheral immune cells from relapsing-remitting and primary progressive MS patients exhibited strongly decreased levels of the bile acid receptor FXR (farnesoid-X-receptor, NR1H4), we evaluated its potential relevance as therapeutic target for control of established CNS autoimmunity. Pharmacological FXR activation promoted generation of anti-inflammatory macrophages characterized by arginase-1, increased IL-10 production, and suppression of T cell responses. In mice, FXR activation ameliorated CNS autoimmunity in an IL-10-dependent fashion and even suppressed advanced clinical disease upon therapeutic administration. In analogy to rodents, pharmacological FXR activation in human monocytes from healthy controls and MS patients induced an anti-inflammatory phenotype with suppressive properties including control of effector T cell proliferation. We therefore, propose an important role of FXR in control of T cell-mediated autoimmunity by promoting anti-inflammatory macrophage responses.

  15. 血管抑素联合丝裂霉素C防止原发性翼状胬肉术后复发的临床疗效观察%The clinical curative effect of primary pterygium's postoperative recurrence by Angiostatin combined with Mitomycin C

    许丹丹; 刘海俊; 李燕; 刘子彬


    目的 观察血管抑素(Angiostatin AS)联合丝裂霉素C(Mitomycin MMC)防止原发性翼状胬肉术后复发的临床疗效.方法 对365例(369眼)原发性翼状胬肉随机分成3组,分别采用A组行逆行性翼状胬肉切除术联合丝裂霉素(121眼),B组行逆行性翼状胬肉切除术联合血管抑素(122眼),C组行逆行性翼状胬肉切除术联合丝裂霉素及血管抑素(126眼)等方法治疗,随访12~18个月,比较其复发率.结果 3组间差异具有显著性意义(P<0.05),C组复发率(0.8%,1/126)最低,其次是B组(5.7%,7/122),最后是A组(7.4%,9/121).结论 逆行性翼状胬肉手术联合丝裂霉素C及血管抑制素治疗原发性翼状胬肉,其疗效显著,复发率低,值得推广.%Objective To study the clinical curative effect of primary pterygium's postoperative recurrence by Angiostatin combined with Mitomycin C. Methods 365 cases (369 eyes) with primary pterygium were divided into three random groups : A group (121 eyes) was treated with retrograde resection combined with M MC; B group (122 eyes) was treated with retrograde resection combined with AS and C group (126 eyes) was treated with retrograde resection combined with AS and MMC. Follow-up of 12- 18 months was carried out, the recurrence rate was then compared. Results The difference among the 3 groups was significant (P<0.05). Group C recurrence rate (0.8%, 1/126 )was minimum, the next was group B (5.7%, 7/122), and the last was group A (7.4%, 9/121). Conclusions The retrograde resection combined with AS and MMC is a distinct effective remedy in treatment of primary pterygium. It can achieve good result reduced the recurrence rate and is , therefore, worth spreading.

  16. Expectativas y satisfacción en el tratamiento del neumotórax espontáneo primario recurrente tratado por toracotomía o cirugía torácica video-asistida Expectations and patient satisfaction related to the use of thoracotomy and video-assisted thoracoscopic surgery for treating recurrence of spontaneous primary pneumothorax

    Jorge Ramón Lucena Olavarrieta


    Full Text Available OBJETIVO: Comparar los resultados de la toracotomía con la video-assisted thoracoscopic surgery (VATS, cirugía torácica video-asistida en el tratamiento de las recurrencias del neumotórax espontáneo primario. MÉTODOS: Se revisaron los expedientes clínicos de los pacientes con neumotórax primario recurrente dividiéndose en dos grupos: pacientes sometidos a toracotomía (n = 53, grupo toracotomía y pacientes sometidos a VATS (n = 47, grupo VATS. RESULTADOS: La morbilidad fue mayor en el grupo A. Sin mortalidad en ninguno de los dos grupos. La duración de la hospitalización fue similar. Los pacientes del grupo toracotomía necesitaron más dosis de narcóticos durante períodos más largos de tiempo que los del grupo VATS (p OBJECTIVE: To compare the outcomes of thoracotomy and video-assisted thoracoscopic surgery (VATS in the treatment of recurrence of primary spontaneous pneumothorax. METHODS: Medical records of patients presenting recurrence of primary spontaneous pneumothorax were retrospectively reviewed. Patients were divided into two groups: those who underwent conservative thoracotomy (n = 53, thoracotomy group; and those who underwent VATS (n = 47, VATS group. RESULTS: Although there were no deaths in either group and the length of hospital stays was similar between the two, there was greater morbidity in the thoracotomy group. Patients in the thoracotomy group required more pain medication for longer periods than did those in the VATS group (p < 0.05. In the thoracotomy group, the rate of recurrence was 3%. Pain was classified as insignificant at one month after the operation by 68% of patients in the VATS group and by only 21% of those in the thoracotomy group (p < 0.05. At three years after the surgical procedure, 97% of the VATS group patients considered themselves completely recovered from the operation, compared with only 79% in the thoracotomy group (p < 0.05. Chronic or intermittent pain, requiring the use of analgesics

  17. Recurrent wheezing in children

    Piazza, Michele; Piacentini, Giorgio


    Recurrent wheezing have a significant morbidity and it’s estimated that about one third of school-age children manifest the symptom during the first 5 years of life. Proper identification of children at risk of developing asthma at school age may predict long-term outcomes and improve treatment and preventive approach, but the possibility to identify these children at preschool age remains limited. For many years authors focused their studies to identify early children with recurrent wheezing at risk to develop asthma at school age. Different phenotypes have been proposed for a more precise characterization and a personalized plan of treatment. The main criticism concerns the inability to define stable phenotypes with the risk of overestimating or underestimating the characteristics of symptoms in these children. The aim of this review is to report the recent developments on the diagnosis and treatment of recurrent paediatric wheezing. PMID:26835404

  18. Recurrence of angular cheilitis.

    Ohman, S C; Jontell, M; Dahlen, G


    The incidence of recurrence of angular cheilitis following a successful antimicrobial treatment was studied in 48 patients. Clinical assessments including a microbial examination were carried out 8 months and 5 yr after termination of treatment. Eighty percent of the patients reported recurrence of their angular cheilitis on one or more occasions during the observation period. Patients with cutaneous disorders associated with dry skin or intraoral leukoplakia had an increased incidence of recrudescence. Neither the presence of denture stomatitis nor the type of microorganisms isolated from the original lesions of angular cheilitis, i.e. Candida albicans and/or Staphylococcus aureus, were associated with the number of recurrences. The present observations indicate that treatment of the majority of patients with angular cheilitis should be considered in a longer perspective than previously supposed, due to the short lasting therapeutic effects of the antimicrobial therapy.

  19. Recurrent Novae - A Review

    Mukai, Koji


    In recent years, recurrent nova eruptions are often observed very intensely in wide range of wavelengths from radio to optical to X-rays. Here I present selected highlights from recent multi-wavelength observations. The enigma of T Pyx is at the heart of this paper. While our current understanding of CV and symbiotic star evolution can explain why certain subset of recurrent novae have high accretion rate, that of T Pyx must be greatly elevated compared to the evolutionary mean. At the same time, we have extensive data to be able to estimate how the nova envelope was ejected in T Pyx, and it turns to be a rather complex tale. One suspects that envelope ejection in recurrent and classical novae in general is more complicated than the textbook descriptions. At the end of the review, I will speculate that these two may be connected.

  20. Induction of Golli-MBP Expression in CNS Macrophages During Acute LPS-Induced CNS Inflammation and Experimental Autoimmune Encephalomyelitis (EAE

    Tracey L. Papenfuss


    Full Text Available Microglia are the tissue macrophages of the CNS. Microglial activation coupled with macrophage infiltration is a common feature of many classic neurodegenerative disorders. The absence of cell-type specific markers has confounded and complicated the analysis of cell-type specific contributions toward the onset, progression, and remission of neurodegeneration. Molecular screens comparing gene expression in cultured microglia and macrophages identified Golli-myelin basic protein (MBP as a candidate molecule enriched in peripheral macrophages. In situ hybridization analysis of LPS/IFNg and experimental autoimmune encephalomyelitis (EAE–induced CNS inflammation revealed that only a subset of CNS macrophages express Golli-MBP. Interestingly, the location and morphology of Golli-MBP+ CNS macrophages differs between these two models of CNS inflammation. These data demonstrate the difficulties of extending in vitro observations to in vivo biology and concretely illustrate the complex heterogeneity of macrophage activation states present in region- and stage-specific phases of CNS inflammation. Taken altogether, these are consistent with the emerging picture that the phenotype of CNS macrophages is actively defined by their molecular interactions with the CNS microenvironment.

  1. Recurrent parotitis in children

    Bhattarai M


    Full Text Available Recurrent parotitis is an uncommon condition in children. Its etiological factors have not been proved till date although causes due to genetic inheritance, local autoimmune manifestation, allergy, viral infection and immunodeficiency have been suggested. The exact management of this disorder is not yet standardized, but a conservative approach is preferred and all affected children should be screened for Sjogren′s syndrome and immune deficiency including human immunodeficiency virus. We report a 12 years female child who presented with 12 episodes of non-painful recurrent swellings of the bilateral parotid gland in the past 3 years.

  2. Tackling a recurrent pinealoblastoma.

    Palled, Siddanna; Kalavagunta, Sruthi; Beerappa Gowda, Jaipal; Umesh, Kavita; Aal, Mahalaxmi; Abdul Razack, Tanvir Pasha Chitraduraga; Gowda, Veerabhadre; Viswanath, Lokesh


    Pineoblastomas are rare, malignant, pineal region lesions that account for <0.1% of all intracranial tumors and can metastasize along the neuroaxis. Pineoblastomas are more common in children than in adults and adults account for <10% of patients. The management of pinealoblastoma is multimodality approach, surgery followed with radiation and chemotherapy. In view of aggressive nature few centres use high dose chemotherapy with autologus stem cell transplant in newly diagnosed cases but in recurrent setting the literature is very sparse. The present case represents the management of pinealoblastoma in the recurrent setting with reirradiation and adjuvant carmustine chemotherapy wherein the management guidelines are not definitive.

  3. Risk factors for recurrence and prognosis of low-grade endometrial adenocarcinoma; vaginal versus other sites.

    Moschiano, Elizabeth J; Barbuto, Denise A; Walsh, Christine; Singh, Kanwaljit; Euscher, Elizabeth D; Roma, Andres A; Ali-Fehmi, Rouba; Frauenhoffer, Elizabeth E; Montiel, Delia P; Kim, Insun; Djordjevic, Bojana; Malpica, Anais; Hong, Sung Ran; Silva, Elvio G


    Endometrial adenocarcinoma is the most common gynecologic cancer in the United States. The prognosis is generally favorable, however, a significant number of patients do develop local or distant recurrence. The most common site of recurrence is vaginal. Our aim was to better characterize patients with vaginal recurrence of low-grade endometrioid adenocarcinoma with respect to associated tumor parameters and clinical outcome. We compiled 255 cases of low-grade (FIGO Grade I or II) endometrioid adenocarcinoma on hysterectomy specimens with lymph node dissection. A total of 113 cases with positive lymph nodes or recurrent disease were included in our study group. Seventy-three cases (13 Grade 1, 60 Grade 2) developed extravaginal recurrence and 40 cases (7 Grade 1, 33 Grade 2) developed vaginal recurrence. We evaluated numerous tumor parameters including: percentage myoinvasion, presence of microcystic, elongated, and fragmented pattern of myoinvasion, lymphovascular space invasion, and cervical involvement. Clinical follow-up showed that 30% (34/113) of all patients with recurrent disease died as a result of their disease during our follow-up period, including 31 (42.5%) with extravaginal recurrence and 3 (7.5%) with primary vaginal recurrence (P=0.001). The 3 patients with vaginal recurrence developed subsequent extravaginal recurrence before death. Vaginal recurrence patients show increased cervical involvement by tumor, but lack other risk factors associated with recurrent disease at other sites. There were no deaths among patients with isolated vaginal recurrence, suggesting that vaginal recurrence is not a marker of aggressive tumor biology.

  4. Comparison of standard and delayed imaging to improve the detection rate of [{sup 68}Ga]PSMA I and T PET/CT in patients with biochemical recurrence or prostate-specific antigen persistence after primary therapy for prostate cancer

    Schmuck, Sebastian; Nordlohne, Stefan; Sohns, Jan M.; Ross, Tobias L.; Bengel, Frank M.; Derlin, Thorsten [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); Klot, Christoph A. von [Hannover Medical School, Department of Urology and Urologic Oncology, Hannover (Germany); Henkenberens, Christoph; Christiansen, Hans [Hannover Medical School, Department of Radiation Oncology, Hannover (Germany); Wester, Hans-Juergen [Technische Universitaet Muenchen, Pharmaceutical Radiochemistry, Garching (Germany)


    The aim of this study was to assess the value of dual-time point imaging in PET/CT for detection of biochemically recurrent or persistent prostate cancer, using the prostate-specific membrane antigen (PSMA) ligand [{sup 68}Ga]PSMA I and T. 240 patients who underwent a [{sup 68}Ga]PSMA I and T PET/CT in the context of biochemical relapse of prostate cancer were included in this retrospective analysis. Imaging consisted of a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified proportions of positive PET/CT results, standardized uptake values and target-to-background ratios were analyzed, and compared between standard and delayed imaging. The overall detection rates of [{sup 68}Ga]PSMA I and T PET/CT were 94.2, 71.8, 58.6, 55.9 and 38.9% for PSA levels of ≥2, 1 to <2, 0.5 to <1, >0.2 to <0.5, and 0.01 to 0.2 ng/mL, respectively. Although the target-to-background ratio improved significantly over time (P < 0.0001), the majority (96.6%) of all lesions suggestive of recurrent disease could already be detected in standard imaging. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 5.4% (10/184) of abnormal [{sup 68}Ga]PSMA I and T PET/CT scans, and exclusively detected 3.4% (38/1134) of all lesions suggestive of recurrent disease. [{sup 68}Ga]PSMA I and T PET/CT shows high detection rates in patients with prostate-specific antigen persistence or biochemical recurrence of prostate cancer. Delayed imaging can detect lesions with improved contrast compared to standard imaging. However, the impact on detection rates was limited in this study. (orig.)

  5. Phase I Trial of MK-0752 in Children With Refractory CNS Malignancies: A Pediatric Brain Tumor Consortium Study

    Fouladi, Maryam; Stewart, Clinton F.; Olson, James; Wagner, Lars M.; Onar-Thomas, Arzu; Kocak, Mehmet; Packer, Roger J.; Goldman, Stewart; Gururangan, Sridharan; Gajjar, Amar; Demuth, Tim; Kun, Larry E.; Boyett, James M.; Gilbertson, Richard J.


    Purpose To estimate the maximum-tolerated dose (MTD), describe dose-limiting toxicities (DLTs), and characterize pharmacokinetic properties of MK-0752, a gamma secretase inhibitor, in children with refractory or recurrent CNS malignancies. Patients and Methods MK-0752 was administered once daily for 3 consecutive days of every 7 days at escalating dosages starting at 200 mg/m2. The modified continual reassessment method was used to estimate the MTD. A course was 28 days in duration. Pharmacokinetic analysis was performed during the first course. Expression of NOTCH and hairy enhancer of split (HES) proteins was assessed in peripheral-blood mononuclear cells (PBMCs) before and following treatment with MK-0752. Results Twenty-three eligible patients were enrolled: 10 males (median age, 8.1 years; range, 2.6 to 17.7 years) with diagnoses of brainstem glioma (n = 6), ependymoma (n = 8), medulloblastoma/primitive neuroectodermal tumor (n = 4), glioblastoma multiforme (n = 2), atypical teratoid/rhabdoid tumor (n = 1), malignant glioma (n = 1), and choroid plexus carcinoma, (n = 1). Seventeen patients were fully evaluable for toxicity. No DLTs occurred in the three patients enrolled at 200 mg/m2/dose. At 260 mg/m2/dose, DLTs occurred in two of six patients, both of whom experienced grade 3 ALT and AST. There were no grade 4 toxicities; non–dose-limiting grade 3 toxicities included hypokalemia and lymphopenia. Population pharmacokinetic values (% coefficient of variation) for MK-0752 were apparent oral clearance, 0.444 (38%) L/h/m2; apparent volume of distribution, 7.36 (24%) L/m2; and ka, 0.358 (99%) hr−1. Conclusion MK-0752 is well-tolerated in children with recurrent CNS malignancies. The recommended phase II dose using the 3 days on followed by 4 days off schedule is 260 mg/m2/dose once daily. PMID:21825264

  6. Dynamics of chemosensitivity and chromosomal instability in recurrent glioblastoma.

    Spiegl-Kreinecker, S; Pirker, C; Marosi, C; Buchroithner, J; Pichler, J; Silye, R; Fischer, J; Micksche, M; Berger, W


    Glioblastoma multiforme is characterised by invasive growth and frequent recurrence. Here, we have analysed chromosomal changes in comparison to tumour cell aggressiveness and chemosensitivity of three cell lines established from a primary tumour and consecutive recurrences (BTL1 to BTL3) of a long-term surviving glioblastoma patient together with paraffin-embedded materials of five further cases with recurrent disease. Following surgery, the BTL patient progressed under irradiation/ lomustine but responded to temozolomide after re-operation to temozolomide. The primary tumour -derived BTL1 cells showed chromosomal imbalances typical of highly aggressive glioblastomas. Interestingly, BTL2 cells established from the first recurrence developed under therapy showed signs of enhanced chromosomal instability. In contrast, BTL3 cells from the second recurrence resembled a less aggressive subclone of the primary tumour. Although BTL2 cells exhibited a highly aggressive phenotype, BTL3 cells were characterised by reduced proliferative and migratory potential. Despite persistent methylation of the O6-methylguanine-DNA methyltransferase promoter, BTL3 cells exhibited the highest temozolomide sensitivity. A comparable situation was found in two out of five glioblastoma patients, both characterised by enhanced survival time, who also relapsed after surgery/chemotherapy with less aggressive recurrences. Taken together, our data suggest that pretreated glioblastoma patients may relapse with highly chemosensitive tumours confirming the feasibility of temozolomide treatment even in case of repeated recurrence.

  7. Endovascular transplantation of stem cells to the injured rat CNS

    Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan [Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Department of Neuroradiology, Stockholm (Sweden); Le Blanc, Katarina [Karolinska University Hospital, Department of Stem Cell Research, Karolinska Institutet, Department of Clinical Immunology, Stockholm (Sweden)


    Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)


    F. Jadali


    Full Text Available ObjectiveTumors of the central nervous system constitute the largest group of solid neoplasms in children and are second only to leukemia in their overall frequency during childhood. The main purpose of the present study is to determine the incidence, age, sex, location and histological diagnosis of CNS tumors in children, less than 15 years of age, in the Mofid Children’s Hospital, in the past 10 years.Materials and Methods In this descriptive retrospective study we reviewed the medical records of 143children with diagnosis of CNS tumors admitted during the past 10 years in neurology and surgery departments of Mofid Children’s Hospital between the years 1996 and 2006.ResultsDuring the 10 year study period, CNS tumor was diagnosed in 143 patients; of these tumors, 119 were intracranial and 58 were intraspinal; 51.3% of brain tumors were located in the supratentorial and 48.7% in the infratentorial regions. The most common intracranial neoplasms were astrocytic tumors (36.8%, embryonal tumors (31.1% and ependymal tumors (13.4%. Of the intraspinal neoplasms the most frequently noted were embryonal tumors (37.5%, mesenchymal meningothelial tumors (20.8%, followed by astrocytic tumors (16.7%. The median age at diagnosis was 8.9 ± 4.1 years with a male to female ratio of 1.4:1 (P<0.5. The most common intracranial astrocytic and embryonal neoplasms were pilocytic astrocytoma and medulloblastoma / PNET respectively.ConclusionBrain tumors in children constitute a diverse group in terms of incidence, distribution and histopathological diagnosis.

  9. New perspectives on using brain imaging to study CNS stimulants.

    Lukas, Scott E


    While the recent application of brain imaging to study CNS stimulants has offered new insights into the fundamental factors that contribute to their use and abuse, many gaps remain. Brain circuits that mediate pleasure, dependence, craving and relapse are anatomically, neurophysiologically and neurochemically distinct from one another, which has guided the search for correlates of stimulant-seeking and taking behavior. However, unlike other drugs of abuse, metrics for tolerance and physical dependence on stimulants are not obvious. The dopamine theory of stimulant abuse does not sufficiently explain this disorder as serotonergic, GABAergic and glutamagergic circuits are clearly involved in stimulant pharmacology and so tracking the source of the "addictive" processes must adopt a more multimodal, multidisciplinary approach. To this end, both anatomical and functional magnetic resonance imaging (MRI), MR spectroscopy (MRS) and positron emission tomography (PET) are complementary and have equally contributed to our understanding of how stimulants affect the brain and behavior. New vistas in this area include nanotechnology approaches to deliver small molecules to receptors and use MRI to resolve receptor dynamics. Anatomical and blood flow imaging has yielded data showing that cognitive enhancers might be useful adjuncts in treating CNS stimulant dependence, while MRS has opened opportunities to examine the brain's readiness to accept treatment as GABA tone normalizes after detoxification. A desired outcome of the above approaches is being able to offer evidence-based rationales for treatment approaches that can be implemented in a more broad geographic area, where access to brain imaging facilities may be limited. This article is part of the Special Issue entitled 'CNS Stimulants'.

  10. Recurrent Glioblastomas Reveal Molecular Subtypes Associated with Mechanistic Implications of Drug-Resistance.

    So Mee Kwon

    Full Text Available Previously, transcriptomic profiling studies have shown distinct molecular subtypes of glioblastomas. It has also been suggested that the recurrence of glioblastomas could be achieved by transcriptomic reprograming of tumors, however, their characteristics are not yet fully understood. Here, to gain the mechanistic insights on the molecular phenotypes of recurrent glioblastomas, gene expression profiling was performed on the 43 cases of glioblastomas including 15 paired primary and recurrent cases. Unsupervised clustering analyses revealed two subtypes of G1 and G2, which were characterized by proliferation and neuron-like gene expression traits, respectively. While the primary tumors were classified as G1 subtype, the recurrent glioblastomas showed two distinct expression types. Compared to paired primary tumors, the recurrent tumors in G1 subtype did not show expression alteration. By contrast, the recurrent tumors in G2 subtype showed expression changes from proliferation type to neuron-like one. We also observed the expression of stemness-related genes in G1 recurrent tumors and the altered expression of DNA-repair genes (i.e., AURK, HOX, MGMT, and MSH6 in the G2 recurrent tumors, which might be responsible for the acquisition of drug resistance mechanism during tumor recurrence in a subtype-specific manner. We suggest that recurrent glioblastomas may choose two different strategies for transcriptomic reprograming to escape the chemotherapeutic treatment during tumor recurrence. Our results might be helpful to determine personalized therapeutic strategy against heterogeneous glioma recurrence.

  11. Achieving Control of Lesion Growth in CNS with Minimal Damage

    Raja, Mathankumar


    Lesions in central nervous system (CNS) and their growth leads to debilitating diseases like Multiple Sclerosis (MS), Alzheimer's etc. We developed a model earlier which shows how the lesion growth can be arrested through a beneficial auto-immune mechanism. The success of the approach depends on a set of control parameters and their phase space was shown to have a smooth manifold separating the uncontrolled lesion growth region from the controlled. Here we show that an optimal set of parameter values exist which minimizes system damage while achieving control of lesion growth.

  12. Metallothionein Expression and Roles During Neuropathology in the CNS

    Penkowa, Milena


    effects are obtained after brain injury by using native or recombinant MT-I or MT-II derived from diverse non-mammalian and mammalian species like drosophila, mouse, rabbit, horse and human. Treatment with these MT-I and MT-II proteins significantly reduce inflammation, oxidative stress, neurodegeneration...... and apoptotic cell death after brain injury, while astroglia is stimulated. This indicates that MT-I+II function independently of species of origin. Previously, we showed that MT-I+II also ameliorate autoimmune, excitotoxic and inflammatory CNS disorders, and independent groups have confirmed this and have...

  13. Lung Cancer Indicators Recurrence

    This study describes prognostic factors for lung cancer spread and recurrence, as well as subsequent risk of death from the disease. The investigators observed that regardless of cancer stage, grade, or type of lung cancer, patients in the study were more

  14. Chronic recurrent multifocal osteomyelitis

    Wedman, Jan; van Weissenbruch, Ranny


    We report what is, to our best knowledge, the first case of chronic recurrent multifocal osteomyelitis (CRMO) in which the frontal and sphenoid bones were involved. Characterized by a prolonged and fluctuating course of osteomyelitis at different sites, CRMO is self-limited, although sequelae can oc

  15. Recurrent Gliosarcoma in Pregnancy


    Gliosarcoma is a rare tumor of the central nervous system and it constitutes about 1 to 8% of all malignant gliomas. In this report we are presenting a recurrent gliosarcoma case during a pregnancy in a 30-year-old woman. This is the first report presenting gliosarcoma in the pregnancy.

  16. Recurrent gallstone ileus.

    Hayes, Nicolas; Saha, Sanjoy


    Mechanical small bowel obstructions caused by gallstones account for 1% to 3% of cases. In these patients, 80% to 90% of residual gallstones in these patients will pass through a remaining fistula without consequence. Recurrent gallstone ileus has been reported in 5% of patients. We report the case of a woman, aged 72 years, who presented with mechanical small bowel obstruction caused by gallstone ileus. After successful surgical therapy for gallstone ileus, the patient's symptoms recurred, and she was diagnosed with recurrent gallstone ileus requiring a repeat operation. While management of gallstone ileus can be achieved through a single-stage operation including enterolithotomy and cholecystectomy with repair of biliary-enteric fistula or by enterolithotomy alone, the literature supports enterolithotomy alone as the treatment of choice for gallstone ileus due to decreased mortality and morbidity. However, the latter approach does not obviate potential recurrence. We present this case of recurrent gallstone ileus to elucidate and review the pathogenesis, presentation, diagnosis, and consensus recommendations regarding management of this disorder.

  17. Acute Recurrent Pancreatitis

    Glen A Lehman


    Full Text Available History, physical examination, simple laboratory and radiological tests, and endoscopic retrograde cholangiopancreatography (ERCP are able to establish the cause of recurrent acute pancreatitis in 70% to 90% of patients. Dysfunction of the biliary and/or pancreatic sphincter, as identified by sphincter of Oddi manometry, accounts for the majority of the remaining cases. The diagnosis may be missed if the pancreatic sphincter is not evaluated. Pancreas divisum is a prevalent congenital abnormality that is usually innocuous but can lead to recurrent attacks of acute pancreatitis or abdominal pain. In select cases, endoscopic sphincterotomy of the minor papilla can provide relief of symptoms and prevent further attacks. A small proportion of patients with idiopathic pancreatitis have tiny stones in the common bile duct (microlithiasis. Crystals can be visualized during microscopic analysis of bile that is aspirated at the time of ERCP. Neoplasia is a rare cause of pancreatitis, and the diagnosis can usually be established by computerized tomography or ERCP. A wide variety of medications can also cause recurrent pancreatitis. ERCP, sphincter of Oddi manometry, and microscopy of aspirated bile should be undertaken in patients with recurrent pancreatitis in whom the diagnosis is not obvious.

  18. Recurrent Spatial Transformer Networks

    Sønderby, Søren Kaae; Sønderby, Casper Kaae; Maaløe, Lars;


    We integrate the recently proposed spatial transformer network (SPN) [Jaderberg et. al 2015] into a recurrent neural network (RNN) to form an RNN-SPN model. We use the RNN-SPN to classify digits in cluttered MNIST sequences. The proposed model achieves a single digit error of 1.5% compared to 2...

  19. The role of mast cells in vascularized recurrent pterygium

    Ali Riza Cenk Celebi


    Full Text Available Objective: To determine and compare the mast cell count in primary and recurrent vascularized pterygium, and in normal bulbar conjunctiva. Methods: The study included 22 patients with primary pterygium (PP group and 28 patients with vascularized recurrent pterygium (VRP group that underwent excision via the limbal conjunctival autograft technique. Normal conjunctiva samples were collected from the superotemporal bulbar conjunctival region, just temporal to the site from which the autograft conjunctival tissue was harvested. The total number of mast cells in the pterygium (primary and recurrent and control tissue samples was calculated microscopically using 1% toluidine blue stain under 400× magnification. Results: The mean mast cell count in primary and vascularized recurrent pterygium tissue was 7.45 ± 2.06 mm–2 and 16.11 ± 4.33 mm–2, respectively, and the difference was significant (independent samples t-test, P<0.001. The mean mast cell count in pterygium tissue was significantly higher than that in normal conjunctiva tissue in both groups (Student's t-test, P<0.001. Conclusion: An increase in the number of mast cells might play a role in the pathogenesis of recurrent pterygium. Determination of a mast cell count cut-off value could be of diagnostic significance for recurrent pterygium.

  20. Direct inguinal hernias and anterior surgical approach are risk factors for female inguinal hernia recurrences.

    Burcharth, Jakob; Andresen, Kristoffer; Pommergaard, Hans-Christian; Bisgaard, Thue; Rosenberg, Jacob


    The purpose of this study was to establish the risk of recurrence after direct and indirect inguinal hernia operation in a large-scale female population and to establish the relationship between the type of hernia at the primary and recurrent procedure. Using data from the Danish Hernia Database (DHDB), a cohort was generated: all females operated on electively for a primary inguinal hernia by either Lichtenstein’s technique or laparoscopy from 1998 to 2012. Within this prospectively collected cohort, the hernia type at the primary procedure (direct inguinal hernia (DIH), indirect inguinal hernia (IIH), combination hernia), the hernia type at the recurrent procedure (DIH, IIH, combination hernia, femoral hernia), anesthesia type, and time from primary procedure to reoperation were registered. A total of 5,893 females with primary elective inguinal hernia operation on in the study period (61 % IIH, 37 % DIH, 2 % combined hernias) were included with a median follow-up time of 72 months (range 0 to 169). A total of 305 operations for suspected recurrences were registered (61 % inguinal recurrences, 38 % femoral recurrences, 1 % no hernias), which corresponded to an overall reoperation rate of 5.2 %. All femoral recurrences occurred after a previous open anterior operation. The crude reoperation rate after primary DIH operation was 11.0 %, 3.0 % after primary IIH operation and 0.007 % after combined hernia operation (p hernia recurrences exclusively existed after anterior open primary operation.

  1. Simulation and mockup tests for developing TRR-II CNS

    Lee, C. H.; Kawai, T.; Chan, Y. K.; Hong, W. T.; Lee, D. J.; Guung, T. C.; Lan, K. C.


    The Taiwan Research Reactor improvement and the utilization promotion project (TRR-II) with Cold Neutron Source (CNS) was carried out at Institute of Nuclear Energy Research. The CNS with a two-phase thermosiphon loop consists of an annular cylindrical moderator cell, a single moderator transfer tube, and a condenser. The self-regulating characteristics of a two-phase thermosiphon loop are investigated against variations of heat load. The experiments on the thermal-hydraulic characteristics have been performed using a full-scale mockup loop and a Freon-11 was used as a working fluid. Two cases were evaluated by the simulation and experiments. One case is an ORPHEE-type moderator cell in which an inner shell is open at the bottom, the other case is one with an inner cavity with no hole at the bottom but a vapor inlet opening at the uppermost part of the cavity. The flooding limitations, liquid level and void fraction in the moderator cell as a function of the initial Freon-11 inventory and the heat load are also reported.

  2. Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

    Ravi Kant Upadhyay


    Full Text Available Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

  3. Plant Derived Phytocompound, Embelin in CNS Disorders: A Systematic Review.

    Kundap, Uday P; Bhuvanendran, Saatheeyavaane; Kumari, Yatinesh; Othman, Iekhsan; Shaikh, Mohd Farooq


    A Central nervous system (CNS) disease is the one which affects either the spinal cord or brain and causing neurological or psychiatric complications. During the nineteenth century, modern medicines have occupied the therapy for many ailments and are widely used these days. Herbal medicines have often maintained popularity for historical and cultural reasons and also considered safer as they originate from natural sources. Embelin is a plant-based benzoquinone which is the major active constituent of the fruits of Embelia ribes Burm. It is an Indo-Malaysian species, extensively used in various traditional medicine systems for treating various diseases. Several natural products including quinone derivatives, which are considered to possess better safety and efficacy profile, are known for their CNS related activity. The bright orange hydroxybenzoquinone embelin-rich fruits of E. ribes have become popular in ethnomedicine. The present systematic review summarizes the effects of embelin on central nervous system and related diseases. A PRISMA model for systematic review was utilized for search. Various electronic databases such as Pubmed, Springer, Scopus, ScienceDirect, and Google Scholar were searched between January 2000 and February 2016. Based on the search criteria for the literature, 13 qualified articles were selected and discussed in this review. The results of the report showed that there is a lack of translational research and not a single study was found in human. This report gives embelin a further way to be explored in clinical trials for its safety and efficacy.

  4. Emerging tumor entities and variants of CNS neoplasms.

    Cenacchi, Giovanna; Giangaspero, Felice


    Since the appearance in 2000 of the World Health Organization (WHO) classification for central nervous system (CNS) neoplasms, numerous descriptions of new entities or variants have appeared in the literature. In the group of neuronal and mixed glioneuronal neoplasms are lesions with distinctive morphological features that are still not included in a precise classification, including extraventricular neurocytoma, papillary glioneuronal tumor, rosette-forming glioneuronal of the fourth ventricle, glioneuronal with neuropil-like rosette, and DNT-like tumor of the septum pellucidum. The glioneuronal tumor with neuropil-like rosette and oligodendroglioma with neurocytic differentiation represent morphological variants of genetically proven diffuse gliomas. The lipoastrocytoma and the pilomixoid astrocytoma enlarge the group of astrocytic lesions. Rare, low-grade gliomas of the spinal cord with extensive leptomeningeal dissemination associated with unusual neuroimaging are described. The chordoid glioma of the third ventricle and the papillary tumor of the pineal region seem to be correlated by a common histogenesis from the specialized ependyma of the subcommissural organ. An embryonal tumor with neuropil and true rosettes combining features of neuroblastoma and ependymoblastoma is discussed. These new, recently described lesions indicate that the complex morphologic spectrum of CNS tumors is far from being completely delineated.

  5. The Role of Rho GTPase Proteins in CNS Neuronal Migration

    Govek, Eve-Ellen; Hatten, Mary E.; Van Aelst, Linda


    The architectonics of the mammalian brain arise from a remarkable range of directed cell migrations, which orchestrate the emergence of cortical neuronal layers and pattern brain circuitry. At different stages of cortical histogenesis, specific modes of cell motility are essential to the stepwise formation of cortical architecture. These movements range from interkinetic nuclear movements at the ventricular zone (VZ), to migrations of early-born, postmitotic polymorphic cells into the preplate, to the radial migration of precursors of cortical output neurons across the thickening cortical wall, and the vast, tangential migrations of interneurons from the basal forebrain into the emerging cortical layers. In all cases, acto-myosin motors act in concert with cell adhesion receptor systems to provide the force and traction needed for forward movement. As key regulators of actin and microtubule cytoskeletons, cell polarity, and adhesion, the Rho GTPases play a critical role in CNS neuronal migration. This review will focus on the different types of migration in the developing neocortex and cerebellar cortex, and the role of the Rho GTPases, their regulators and effectors in these CNS migrations, with particular emphasis on their involvement in radial migration. PMID:21557504

  6. Plant Derived Phytocompound, Embelin in CNS Disorders: A Systematic Review

    Kundap, Uday P.; Bhuvanendran, Saatheeyavaane; Kumari, Yatinesh; Othman, Iekhsan; Shaikh, Mohd. Farooq


    A Central nervous system (CNS) disease is the one which affects either the spinal cord or brain and causing neurological or psychiatric complications. During the nineteenth century, modern medicines have occupied the therapy for many ailments and are widely used these days. Herbal medicines have often maintained popularity for historical and cultural reasons and also considered safer as they originate from natural sources. Embelin is a plant-based benzoquinone which is the major active constituent of the fruits of Embelia ribes Burm. It is an Indo-Malaysian species, extensively used in various traditional medicine systems for treating various diseases. Several natural products including quinone derivatives, which are considered to possess better safety and efficacy profile, are known for their CNS related activity. The bright orange hydroxybenzoquinone embelin-rich fruits of E. ribes have become popular in ethnomedicine. The present systematic review summarizes the effects of embelin on central nervous system and related diseases. A PRISMA model for systematic review was utilized for search. Various electronic databases such as Pubmed, Springer, Scopus, ScienceDirect, and Google Scholar were searched between January 2000 and February 2016. Based on the search criteria for the literature, 13 qualified articles were selected and discussed in this review. The results of the report showed that there is a lack of translational research and not a single study was found in human. This report gives embelin a further way to be explored in clinical trials for its safety and efficacy. PMID:28289385

  7. MAG, myelin and overcoming growth inhibition in the CNS.

    Lisa eMcKerracher


    Full Text Available While neurons in the central nervous system have the capacity to regenerate their axons after injury, they fail to do so, in part because regeneration is limited by growth inhibitory proteins present in CNS myelin. Myelin-associated glycoprotein (MAG was the first myelin-derived growth inhibitory protein identified, and its inhibitory activity was initially elucidated in 1994 independently by the Filbin lab and the McKerracher lab using cell-based and biochemical techniques, respectively. Since that time we have gained a wealth of knowledge concerning the numerous growth inhibitory proteins that are present in myelin, and we also have dissected many of the neuronal signaling pathways that act as stop signs for axon regeneration. Here we give an overview of the early research efforts that led to the identification of myelin-derived growth inhibitory proteins, and the importance of this family of proteins for understanding neurotrauma and CNS diseases. We further provide an update on how this knowledge has been translated towards current clinical studies in regenerative medicine.

  8. MicroRNAs as biomarkers for CNS disease

    Pooja eRao


    Full Text Available For many neurological diseases, the efficacy and outcome of treatment depend on early detection. Diagnosis is currently based on the detection of symptoms and neuroimaging abnormalities, which appear at relatively late stages in the pathogenesis. However, the underlying molecular responses to genetic and environmental insults begin much earlier and non-coding RNA networks are critically involved in these cellular regulatory mechanisms. Profiling RNA expression patterns could thus facilitate presymptomatic disease detection.Obtaining indirect readouts of pathological processes is particularly important for brain disorders because of the lack of direct access to tissue for molecular analyses. Living neurons and other CNS cells secrete microRNA and other small non-coding RNA into the extracellular space packaged in exosomes, microvesicles or lipoprotein complexes. This discovery, together with the rapidly evolving massive sequencing technologies that allow detection of virtually all RNA species from small amounts of biological material, has allowed significant progress in the use of extracellular RNA as a biomarker for CNS malignancies, neurological and psychiatric diseases. There is also recent evidence that the interactions between external stimuli and brain pathological processes may be reflected in peripheral tissues, facilitating their use as potential diagnostic markers. In this review, we explore the possibilities and challenges of using microRNA and other small RNAs as a signature for neurodegenerative and other neuropsychatric conditions.

  9. Increased risk of ventral hernia recurrence after pregnancy

    Oma, Erling; Jensen, Kristian K.; Jorgensen, Lars N.


    Background: Female patients of reproductive age constitute a substantial portion of patients undergoing ventral hernia repair, however the impact of pregnancy on the risk of recurrence is scarcely documented. The aim of the study was to evaluate if pregnancy following ventral hernia repair...... was associated with an increased risk of recurrence. Methods: This nationwide cohort study included all female patients of reproductive age registered in the Danish Ventral Hernia Database with ventral hernia repair between 2007 and 2013. The primary outcome was ventral hernia recurrence. Multivariable extended...... of pregnancy on the risk of recurrence is scarcely documented. In this cohort study based on nationwide Danish registries, we found that pregnancy after ventral hernia repair was independently associated with an increased risk of ventral hernia recurrence....

  10. Mammaglobin-A immunohistochemistry in primary central nervous system neoplasms and intracranial metastatic breast carcinoma.

    Cimino, Patrick J; Perrin, Richard J


    Metastases represent the most common type of intracranial neoplasm. In women, 30% of such tumors derive from breast carcinoma. In neurosurgical cases with ambiguous cellular morphology and/or limited biopsy material, immunohistochemistry (IHC) is often performed to distinguish metastases from primary central nervous system (CNS) neoplasms. IHC for mammaglobin-A (MGA), a protein expressed in a majority of breast carcinomas, is commonly applied in this setting, but its utility for distinguishing primary CNS neoplasms from metastatic breast carcinoma is unknown; the reactivity of MGA in primary and metastatic CNS neoplasms has never been described. Here, we describe the frequency and patterns of IHC reactivity for MGA in metastatic and primary CNS neoplasms from patients with well-documented histories of breast carcinoma. Following a published protocol previously applied to non-CNS neoplasms, MGA staining of moderate to strong intensity within 5% or more of a neoplasm was considered positive. On the basis of these criteria, 3 of 12 (25.0%) glioblastomas, 1 of 10 (10.0%) meningiomas, and 47 of 95 (49.5%) metastases were positive. Importantly, the cytoarchitectural staining characteristics among all 4 MGA-positive primary CNS neoplasms (cytoplasmic and nuclear) differed from those of the metastases (cytoplasmic and membranous). These findings suggest that MGA IHC staining intensity and distribution can distinguish metastases from primary CNS neoplasms (P=0.0086) in women with a history of breast carcinoma but also indicate that cytologic staining patterns must be interpreted for more accurate tumor classification.

  11. Coping with Fear of Recurrence

    ... What Comes Next After Finishing Treatment Coping With Fear of Recurrence Having a Baby After Cancer: Pregnancy ... treatment and preparing for the future. Coping With Fear of Recurrence Learn ways to manage the fear ...

  12. Microwave hyperthermia radiosensitized iridium-192 for recurrent brain malignancy.

    Borok, T L; Winter, A; Laing, J; Paglione, R; Sterzer, F; Sinclair, I; Plafker, J


    Twenty-one patients whose solitary detectable biopsy proven recurrent brain malignancies produced Central Nervous System (CNS) symptoms warranting further intervention received 60-minute 43 degrees C (180 degree-minute) interstitial 2450 MHz microwave hyperthermia fractions. All received brain teletherapy prior to recurrence. The first 15 received no brachytherapy and served as a toxicity pilot. All 15 enjoyed neurologic improvement, 12 symptomatic improvement, and 12 objective response as mass reduction and/or tumor necrosis. The next 6 patients were selected with more favorable Karnofsky performance status, no known active malignancy elsewhere, and received afterloading Ir-192 interstitial implantation juxtaposed to radiosensitizing hyperthermia. Volume dose varied from 1000 to 2245 rad, and dose rate from 40 to 100 rad/hr. Dose selected varied as a function of pre-recurrence teletherapy dose, general condition, histologic type, and volume. Neurosurgical debulking, if technically indicated through no additional aperture or trauma, was permitted if consistent with preservation of neurological function. Six enjoyed neurologic improvement, symptom reduction, and objective tumor response; three remain alive, and one experienced transient improvement. Complications, histologic subtypes, autopsy findings, stereotactic approach, thermal monitoring methods and CT follow-up of objective response are presented along with computer dosimetry and isotherm chart. Our microtraumatic universal catheter technique for CT guided stereotactic biopsy, aspiration, decompression, thermal sensory loop, thermalization antennae, and brachytherapy without multiple trauma nor changing catheters is stressed. The rationale for combined modes peculiar to the CNS will be outlined.2+ Proposal for incorporating controlled-release ARA-C chemotherapy polymer micro-rods into the interstitial format will be offered. The preceeding is an FDA-approved controlled clinical trial.(ABSTRACT TRUNCATED AT

  13. 鼻咽癌局部复发或残留患者挽救手术进路的选择%Choice of surgical approaches for salvage surgery of primary lesion recurrence and residual cases of nasopharyngeal carcinoma

    陶仲强; 司勇锋; 蓝胜勇; 张政; 邓卓霞; 黄波; 周日晶; 陆锦龙


    目的 根据鼻咽癌局部复发和残留累及的部位和范围,选择不同手术进路切除肿瘤,观察治疗效果、并发症,并观察其预后.方法 回顾性分析从1991年3月至2005年1月因首次治疗失败、手术挽救治疗的鼻咽癌患者37例,男23例,女14例;年龄26~57岁,中位年龄46.5岁.Ⅰ期4例,Ⅱ期10例,Ⅲ期14例,Ⅳ期9例.5例患者颈部淋巴结复发.37例患者经活检证实为鼻咽癌复发和残留.行鼻内镜手术8例,硬腭进路12例,上颌骨外翻进路5例,上颌骨外翻进路+翼点入路4例,鼻侧切+冠状切口双额开颅进路2例,面中部切口鼻锥体翻转进路6例.其中5例同时行颈淋巴清扫术.31例术后2周放疗60 Gy,其中放疗同期化疗15例;6例切缘组织为阴性者未予放疗及化疗.中位随访时间45个月(12~72个月).Kaplan-Meier法计算生存率.结果91.8%(34/37)患者复发肿瘤完全切除,次全切除8.2%(3/37).手术并发症发生率24.3%(9/37).总的3年和5年无瘤生存率分别为62.1%和43.3%.总的3年和5年生存率分别为72.9%和51.3%.Ⅰ~Ⅳ期复发患者的5年无瘤生存率分别为100%、40%、28%和1l%(χ2=10.0,P<0.01=,5年累积生存率为100%、70%、35%和28%(χ2=11.5,P<0.01),差异有统计学意义.结论鼻咽癌复发手术挽救治疗是可行的.根据鼻咽癌复发灶具体部位和范围,采用一种手术进路方法或加以改良,或联合神经外科进路,术中使肿瘤充分暴露,可以安全切除病变,挽救局部复发晚期鼻咽癌患者.%Objective The choice of surgical approaches for salvage surgery based on the location and invasion of recurrent and residual lesions of nasopharyngeal carcinoma (NPC),surgical results,complications,and survival were assessed.Methods Thirty-seven cases with recurrent and residual lesions of NPC underwent salvage surgery between March 1991 and January 2005 were analysed retrospectively.Of 37 patients,23 were men and 14 women,with a median age of 46.5 years (26

  14. Chaotic diagonal recurrent neural network

    Wang Xing-Yuan; Zhang Yi


    We propose a novel neural network based on a diagonal recurrent neural network and chaos,and its structure andlearning algorithm are designed.The multilayer feedforward neural network,diagonal recurrent neural network,and chaotic diagonal recurrent neural network are used to approach the cubic symmetry map.The simulation results show that the approximation capability of the chaotic diagonal recurrent neural network is better than the other two neural networks.

  15. Clinical features, outcomes, and cerebrospinal fluid findings in adult patients with central nervous system (CNS) infections caused by varicella-zoster virus: comparison with enterovirus CNS infections.

    Hong, Hyo-Lim; Lee, Eun Mi; Sung, Heungsup; Kang, Joong Koo; Lee, Sang-Ahm; Choi, Sang-Ho


    Varicella-zoster virus (VZV) is known to be associated with central nervous system (CNS) infections in adults. However, the clinical characteristics of VZV CNS infections are not well characterized. The aim of this study was to compare the clinical manifestations, outcomes, and cerebrospinal fluid (CSF) findings in patients with VZV CNS infections with those in patients with enterovirus (EV) CNS infections. This retrospective cohort study was performed at a 2,700-bed tertiary care hospital. Using a clinical microbiology computerized database, all adults with CSF PCR results positive for VZV or EV that were treated between January 1999 and February 2013 were identified. Thirty-eight patients with VZV CNS infection and 68 patients with EV CNS infection were included in the study. Compared with the EV group, the median age in the VZV group was higher (VZV, 35 years vs. EV, 31 years; P = 0.02), and showed a bimodal age distribution with peaks in the third and seventh decade. Encephalitis was more commonly encountered in the VZV group (VZV, 23.7% vs. EV, 4.4%; P = 0.01). The median lymphocyte percentage in the CSF (VZV, 81% vs. EV, 36%; P < 0.001) and the CSF protein level (VZV, 100 mg/dl vs. EV, 46 mg/dl; P < 0.001) were higher in the VZV group. Compared with patients with EV CNS infection, patients with VZV CNS infection developed encephalitis more often and exhibited more intense inflammatory reaction. Nevertheless, both VZV and EV CNS infections were associated with excellent long-term prognosis. © 2014 Wiley Periodicals, Inc.

  16. Immunomodulators to treat recurrent miscarriage

    Prins, Jelmer R.; Kieffer, Tom E.C.; Scherjon, Sicco A.


    Recurrent miscarriage is a reproductive disorder affecting many couples. Although several factors are associated with recurrent miscarriage, in more than 50% of the cases the cause is unknown. Maladaptation of the maternal immune system is associated with recurrent miscarriage and could explain part

  17. Imaging of recurrent prostate cancer

    Futterer, J.J.


    Approximately 30\\% of patients who underwent radical prostatectomy or radiation therapy will develop biochemical recurrent disease. Biochemical recurrent disease is defined as an increase in the serum value of prostate-specific antigen (PSA) after reaching the nadir. Prostate recurrence can present

  18. Immunomodulators to treat recurrent miscarriage

    Prins, Jelmer R.; Kieffer, Tom E. C.; Scherjon, Sicco A.


    Recurrent miscarriage is a reproductive disorder affecting many couples. Although several factors are associated with recurrent miscarriage, in more than 50% of the cases the cause is unknown. Maladaptation of the maternal immune system is associated with recurrent miscarriage and could explain part

  19. Training Recurrent Networks

    Pedersen, Morten With


    Training recurrent networks is generally believed to be a difficult task. Excessive training times and lack of convergence to an acceptable solution are frequently reported. In this paper we seek to explain the reason for this from a numerical point of view and show how to avoid problems when tra...... training. In particular we investigate ill-conditioning, the need for and effect of regularization and illustrate the superiority of second-order methods for training......Training recurrent networks is generally believed to be a difficult task. Excessive training times and lack of convergence to an acceptable solution are frequently reported. In this paper we seek to explain the reason for this from a numerical point of view and show how to avoid problems when...

  20. Spatial recurrence plots.

    Vasconcelos, D B; Lopes, S R; Viana, R L; Kurths, J


    We propose an extension of the recurrence plot concept to perform quantitative analyzes of roughness and disorder of spatial patterns at a fixed time. We introduce spatial recurrence plots (SRPs) as a graphical representation of the pointwise correlation matrix, in terms of a two-dimensional spatial return plot. This technique is applied to the study of complex patterns generated by coupled map lattices, which are characterized by measures of complexity based on SRPs. We show that the complexity measures we propose for SRPs provide a systematic way of investigating the distribution of spatially coherent structures, such as synchronization domains, in lattice profiles. This approach has potential for many more applications, e.g., in surface roughness analyzes.

  1. Recurrent Syncope due to Esophageal Squamous Cell Carcinoma


    Syncope is caused by a wide variety of disorders. Recurrent syncope as a complication of malignancy is uncommon and may be difficult to diagnose and to treat. Primary neck carcinoma or metastases spreading in parapharyngeal and carotid spaces can involve the internal carotid artery and cause neurally mediated syncope with a clinical presentation like carotid sinus syndrome. We report the case of a 76-year-old man who suffered from recurrent syncope due to invasion of the right carotid sinus b...

  2. Poor Prognosis After Second Locoregional Recurrences in the CALOR Trial.

    Wapnir, Irene L; Gelber, Shari; Anderson, Stewart J; Mamounas, Eleftherios P; Robidoux, André; Martín, Miguel; Nortier, Johan W R; Geyer, Charles E; Paterson, Alexander H G; Láng, István; Price, Karen N; Coates, Alan S; Gelber, Richard D; Rastogi, Priya; Regan, Meredith M; Wolmark, Norman; Aebi, Stefan


    Isolated locoregional recurrences (ILRRs) of breast cancer confer a significant risk for the development of distant metastasis. Management practices and second ILRR events in the Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial were investigated. In this study, 162 patients with ILRR were randomly assigned to receive postoperative chemotherapy or no chemotherapy. Descriptive statistics characterize outcomes according to local therapy and the influence of hormone receptor status on subsequent recurrences. Competing risk regression models, Kaplan-Meier estimates, and Cox proportional hazards models were used to evaluate associations between treatment, site of second recurrence, and outcome. The median follow-up period was 4.9 years. Of the 98 patients who received breast-conserving primary surgery 89 had an ipsilateral-breast tumor recurrence. Salvage mastectomy was performed for 73 patients and repeat lumpectomy for 16 patients. Another eight patients had nodal ILRR, and one patient had chest wall ILRR. Among 64 patients whose primary surgery was mastectomy, 52 had chest wall/skin ILRR, and 12 had nodal ILRR. For 15 patients, a second ILRR developed a median of 1.6 years (range 0.08-4.8 years) after ILRR. All second ILRRs occurred for patients with progesterone receptor-negative ILRR. Death occurred for 7 (47 %) of 15 patients with a second ILRR and 19 (51 %) of 37 patients with a distant recurrence. As shown in the multivariable analysis, the significant predictors of survival after either a second ILRR or distant recurrence were chemotherapy for the primary cancer (hazard ratio [HR], 3.55; 95 % confidence interval [CI], 1.15-10.9; p = 0.03) and the interval (continuous) from the primary surgery (HR, 0.87; 95 % CI, 0.75-1.00; p = 0.05). Second ILRRs represented about one third of all recurrence events after ILRR, and all were PR-negative. These second ILRRs and distant metastases portend an unfavorable outcome.

  3. Analgesic, antiinflammatory and CNS depressant activities of sesquiterpenes and a flavonoid glycoside from Polygonum viscosum

    Datta, B K; Datta, S K; Chowdhury, M M; Khan, T H; Kundu, J K; Rashid, M A; Nahar, L; Sarker, S D


    Analgesic, antiinflammatory and CNS depressant activities of four sesquiterpenes, viscosumic acid, viscozulenic acid, viscoazucine and viscoazulone, and a flavonoid glycoside, quercetin-3-O-(6''-feruloyl...

  4. Supraclavicular recurrence after early breast cancer: a curable condition?

    Pedersen, Anders N; Møller, Susanne; Dahl Steffensen, Karina


    The prognosis of ipsilateral supraclavicular lymph node recurrence after early breast cancer appears to be worse than for other loco-regional recurrences, but better than for distant metastases. The purpose of the present study was to investigate the relationship between different types of salvage...... treatment and primary patient characteristics, treatment response, and survival after supraclavicular recurrence (SR) in a large patient population. From the Danish Breast Cancer Cooperative Group treatment database 1977-2003, 305 patients were identified with SR without distant disease as site of first...

  5. Modularity promotes epidemic recurrence

    Jesan, T; Sinha, Sitabhra


    The long-term evolution of epidemic processes depends crucially on the structure of contact networks. As empirical evidence indicates that human populations exhibit strong community organization, we investigate here how such mesoscopic configurations affect the likelihood of epidemic recurrence. Through numerical simulations on real social networks and theoretical arguments using spectral methods, we demonstrate that highly contagious diseases that would have otherwise died out rapidly can persist indefinitely for an optimal range of modularity in contact networks.

  6. Recurrent Gallstone Ileus

    Hayes, Nicolas; Saha, Sanjoy


    Mechanical small bowel obstructions caused by gallstones account for 1% to 3% of cases. In these patients, 80% to 90% of residual gallstones in these patients will pass through a remaining fistula without consequence. Recurrent gallstone ileus has been reported in 5% of patients. We report the case of a woman, aged 72 years, who presented with mechanical small bowel obstruction caused by gallstone ileus. After successful surgical therapy for gallstone ileus, the patient's symptoms recurred, a...

  7. Blood volume changes after radiotherapy of the CNS; Blutvolumenveraenderungen nach Strahlentherapie des zentralen Nervensystems

    Wenz, F. [Radiologische Universitaetsklinik, Heidelberg (Germany); Fuss, M. [Radiologische Universitaetsklinik, Heidelberg (Germany); Scholdei, R. [Radiologische Universitaetsklinik, Heidelberg (Germany); Essig, M. [Abt. Onkologische Diagnostik und Therapie, Deutsches Krebsforschungszentrum, Heidelberg (Germany); Lohr, F. [Radiologische Universitaetsklinik, Heidelberg (Germany); Rempp, K. [Abt. Klinische Neuroradiologie, Univ. Heidelberg (Germany); Brix, G. [Abt. Biophysik und Medizinische Strahlenphysik, Deutsches Krebsforschungszentrum, Heidelberg (Germany); Knopp, M.V. [Abt. Onkologische Diagnostik und Therapie, Deutsches Krebsforschungszentrum, Heidelberg (Germany); Engenhart, R. [Radiologische Universitaetsklinik, Heidelberg (Germany); Wannenmacher, M. [Radiologische Universitaetsklinik, Heidelberg (Germany)


    The pathogenesis of late delayed radiation damage in normal brain tissue is most likely due to damage to the vascular endothelium. The mitotic activity of gliomas was shown to correlate with the tumor induced angiogenesis. Dynamic susceptibility contrast MR imaging (DSC MRI) allows the measurement of the cerebral hemodynamics based on the indicator dilution theory. We describe theory and technique of the method and present our experience with blood volume measurements after irradiation of the CNS. We established a double slice technique on a standard 1.5 T MR system without hardware modifications, which allows an absolute quantification of the blood volume in regions of interest (ROI) within the brain. Fifty-five T2* weighted double slice images were acquired before, during and after bolus injection of Gd-DTPA (0.1 mmol/kg in 5 sec.) using a SD FLASH sequence (simultaneous dual fast low angle shot, TR/TE1/TE2 31/16/25, flip angle 10 ). Concentration-time curves were calculated from the measured signal-time curves. Blood volume values in tissue were normalised and calculated in absolute values (ml/100 g) based on the knowledge of the arterial input function (AIF), which was measured in the brain supplying arteries. The whole procedure requires only 2 to 3 minutes, the time for post processing is about 15 to 20 minutes. Blood volume parameter images of representative cases demonstrate the blood volume changes after radiotherapy. A reduction in blood volume could be observed in normal brain tissue and low-grade gliomas, while recurrent tumors were accompanied by a local increase in blood volume. Radiation induced blood volume changes in the CNS can be measured using dynamic susceptibility contrast MR imaging. The measurements in normal brain tissue allow a functional in-vivo analysis of late delayed radiation reactions of the CNS. (orig.) [Deutsch] Die Pathogenese von Strahlenspaetfolgen am Gehirn wird auf eine Schaedigung der Gefaessendothelien zurueckgefuehrt. Die

  8. Evaluation of Serum Selenium Levels in Children with Recurrent Febril Convulsions

    Erhan Berk


    Full Text Available Introduction: The febrile convulsion (FC occurs in neurologically normal children aged between six months and five years and it is defined as convulsions occurred during fever and in the absence of central nervous system (CNS infection, electrolyte imbalance, diseases affecting directly CNS, and history of afebrile convulsion. The aims of this study were to determine the serum levels of selenium in patients with recurrent FC and to compare them with those of healthy children. Materials and Methods: The study included 61 pediatric patients diagnosed with recurrent FC. At the same session, 54 healthy children who admitted to our pediatric clinic for routine controls without history of fever and convulsion, are assigned as control group. The serum level of selenium was measured by atomic absorption spectrometric method (hydride technique.Results: Mean level of selenium was determined as 67.10±8.87 µg/L in patients and 81.99±13.13 µg/L in control group; the difference was statistically significant (p<0.05. Discussion: The lower serum levels of selenium in patients with recurrent FC may be the cause of triggering of convulsion or may contribute to its recurrence. Further studies are necessary to clarify this relationship. (Jo­ur­nal of Cur­rent Pe­di­at­rics 2011; 9: 110-5

  9. Risk Factors of the Invasive Breast Cancer Locoregional Recurrence

    R. V. Liubota


    Full Text Available Background. The aim of the research was to estimate the frequency of the locoregional breast cancer recurrence appearance, the recurrence-free period continuance, and the 3- and 5-year survival depending on the scope of the surgical intervention, menstrual profile, and histological and molecular-biologic characteristics of the primary tumor. Patients and Methods. Among 218 patients with a breast cancer, 99 patients had breast-conserving surgery (BCS and 119 underwent radical mastectomy (RME; all patients had regional lymphatic nodes dissection. The size and the primary tumor differentiation degree, metastasis presence in the regional lymph nodes, ER expression, PR, and Her/2neu were assessed as the prognostics factors. Results. It was defined that the locoregional recurrence appearance frequency in patients with BCS turned out to be 13%, and in patients after RME it turned out to be 9%; the recurrence-free period continuance was 53±8 months and 56±10 months, respectively. Conclusions. The locoregional cancer recurrence frequency is higher in women with the menstrual function being preserved at the moment of the primary tumor detection than in postmenopausal patients and also in patients having the hyperexpression of the Her/2neu. The ipsilateral cancer recurrence decreases the 3-year survival by 7,1% and the 5-year one by 20,3%, respectively.

  10. Early and late vulval cancer recurrences: Are they different?

    Ragupathy, Kalpana; Grandidge, Lisa; Strelley, Katie; Wang, Huan; Tidy, John


    Vulval cancers are rare, but after primary treatment, known to recur with a high frequency (30%). Clinico-pathological predictors of recurrence have been established to a great extent. However, there is paucity of literature on predictors of early versus late recurrence. We sought to identify such predictors through a retrospective study of vulval cancer recurrences in a single cancer centre over 11 years. Age of women, depth of invasion/site of primary tumour and presence of background VIN/lichen sclerosus do not appear to affect timing of recurrence. However, vulval cancers that recur after 2 years of primary tumour recognition are more likely to be well-differentiated tumours, have undergone radical surgery and have had a closest disease-free margin >1 cm. Late recurrences are entirely local rather than distant metastases and this translates into a better survival as shown in our study (40 months median survival in the early group versus 112 in the late recurrence group).

  11. Primary Hyperoxaluria

    Jérôme Harambat


    Full Text Available Primary hyperoxalurias (PH are inborn errors in the metabolism of glyoxylate and oxalate. PH type 1, the most common form, is an autosomal recessive disorder caused by a deficiency of the liver-specific enzyme alanine, glyoxylate aminotransferase (AGT resulting in overproduction and excessive urinary excretion of oxalate. Recurrent urolithiasis and nephrocalcinosis are the hallmarks of the disease. As glomerular filtration rate decreases due to progressive renal damage, oxalate accumulates leading to systemic oxalosis. Diagnosis is often delayed and is based on clinical and sonographic findings, urinary oxalate assessment, DNA analysis, and, if necessary, direct AGT activity measurement in liver biopsy tissue. Early initiation of conservative treatment, including high fluid intake, inhibitors of calcium oxalate crystallization, and pyridoxine in responsive cases, can help to maintain renal function in compliant subjects. In end-stage renal disease patients, the best outcomes have been achieved with combined liver-kidney transplantation which corrects the enzyme defect.

  12. Bryostatin-1: pharmacology and therapeutic potential as a CNS drug.

    Sun, Miao-Kun; Alkon, Daniel L


    Bryostatin-1 is a powerful protein kinase C (PKC) agonist, activating PKC isozymes at nanomolar concentrations. Pharmacological studies of bryostatin-1 have mainly been focused on its action in preventing tumor growth. Emerging evidence suggests, however, that bryostatin-1 exhibits additional important pharmacological activities. In preclinical studies bryostatin-1 has been shown at appropriate doses to have cognitive restorative and antidepressant effects. The underlying pharmacological mechanisms may involve an activation of PKC isozymes, induction of synthesis of proteins required for long-term memory, restoration of stress-evoked inhibition of PKC activity, and reduction of neurotoxic amyloid accumulation and tau protein hyperphosphorylation. The therapeutic potential of bryostatin-1 as a CNS drug should be further explored.

  13. Alterations in Nitric Oxide Synthase in the Aged CNS

    Junyang Jung


    Full Text Available Aging is associated with neuronal loss, gross weight reduction of the brain, and glial proliferation in the cortex, all of which lead to functional changes in the brain. It is known that oxidative stress is a critical factor in the pathogenesis of aging; additionally, growing evidence suggests that excessive nitric oxide (NO production contributes to the aging process. However, it is still unclear how NO plays a role in the aging process. This paper describes age-related changes in the activity of NADPH-diaphorase (NADPH-d, a marker for neurons containing nitric oxide synthase (NOS, in many CNS regions. Understanding these changes may provide a novel perspective in identifying the aging mechanism.

  14. Programmed cell death in developing human fetal CNS


    The spatial and temporal distributions of programmed cell death (PCD) in developing central nervous system (CNS) of human fetuses ranging from 12 to 39 weeks of gestation were investigated using techniques of flow cytometry and terminal transferase-mediated nick end labeling (TUNEL). The results showed that PCD did occur in every representative brain region of all fetuses examined in different stages. It was found that there were two peaks of PCD appearing at the 12th and 39th weeks respectively, which suggested that the first peak of apoptosis may be involved in the selective elimination of neurons overproduced during the early development and the second may play an important role in establishing the correct neuronal circuitry.

  15. The Coordinated Noninvasive Studies (CNS) Project. Phase 1


    Mitg qEUO EEG sat*dJ6 EEG syfls al EEG lores adj EEO Was sdj ABR III ampCs ABR I empCs ABRIII a mp ABR III amp JLM (38yr female; personal R, family R...nslt qu.O US& qmO ERG iId 11 110 s eb dj AflRflhauapCs ADR m ampCs ABIIIamp AIR R m= J.L. Lauter [CNS Project/AFOSR 88-0352] FINAL REPORT p. 55 HR (22yr...qUO n/ftes qtdO BEG0329 odi EEG s)13 SOi 11G 0i adpS EE 11ws ad ABR III ampCS ABR III emp~s AIR III amp AIR IIIm S3 (45yr female; personal L, family L

  16. Resveratrol Neuroprotection in Stroke and Traumatic CNS injury

    Lopez, Mary; Dempsey, Robert J; Vemuganti, Raghu


    Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple beneficial effects in vertebrates. Particularly, resveratrol was shown to have therapeutic properties in cancer, atherosclerosis and neurodegeneration. Resveratrol-induced benefits are modulated by multiple synergistic pathways that control oxidative stress, inflammation and cell death. Despite the lack of a definitive mechanism, both in vivo and in vitro studies suggest that resveratrol can induce a neuroprotective state when administered acutely or prior to experimental injury to the CNS. In this review, we discuss the neuroprotective potential of resveratrol in stroke, traumatic brain injury and spinal cord injury, with a focus on the molecular pathways responsible for this protection. PMID:26277384

  17. Brain abscess with an unexpected finding: Actinomyces meyeri CNS infection

    Eiset, Andreas Halgreen; Thomsen, Marianne Kragh; Wejse, Christian

    oedema. By MRI an abscess was suspected and the patient was transferred to the department of neurosurgery, where drainage was performed. Microscopy revealed gram-positive cocci and gram-negative rods and iv. treatment with ceftriaxone 4g x 1 and metronidazole 1g x 1 was commenced. Pus cultures showed...... Prevotella spp. and A. meyeri and the initial treatment was changed to penicillin G 5 MIU x 4 and metronidazole 500 mg x 3 for four weeks followed by oral amoxicillin 500 mg x 3 for three months. The abscess regressed on this treatment and there were no CNS related symptoms at three months follow......-up. The source of infection was most likely periodontitis with spread to the lungs from aspiration or oropharyngeal secretion into the respiratory tract, alternatively from haematogenous spread. Conclusions: We report of the successful treatment of a cerebral abscess caused by A. meyeri with narrow spectrum...

  18. CNS myelin wrapping is driven by actin disassembly.

    Zuchero, J Bradley; Fu, Meng-Meng; Sloan, Steven A; Ibrahim, Adiljan; Olson, Andrew; Zaremba, Anita; Dugas, Jason C; Wienbar, Sophia; Caprariello, Andrew V; Kantor, Christopher; Leonoudakis, Dmitri; Leonoudakus, Dmitri; Lariosa-Willingham, Karen; Kronenberg, Golo; Gertz, Karen; Soderling, Scott H; Miller, Robert H; Barres, Ben A


    Myelin is essential in vertebrates for the rapid propagation of action potentials, but the molecular mechanisms driving its formation remain largely unknown. Here we show that the initial stage of process extension and axon ensheathment by oligodendrocytes requires dynamic actin filament assembly by the Arp2/3 complex. Unexpectedly, subsequent myelin wrapping coincides with the upregulation of actin disassembly proteins and rapid disassembly of the oligodendrocyte actin cytoskeleton and does not require Arp2/3. Inducing loss of actin filaments drives oligodendrocyte membrane spreading and myelin wrapping in vivo, and the actin disassembly factor gelsolin is required for normal wrapping. We show that myelin basic protein, a protein essential for CNS myelin wrapping whose role has been unclear, is required for actin disassembly, and its loss phenocopies loss of actin disassembly proteins. Together, these findings provide insight into the molecular mechanism of myelin wrapping and identify it as an actin-independent form of mammalian cell motility.

  19. Activity dependence of spreading depression in the locust CNS.

    Spong, Kristin E; Mazzetti, Tom R; Robertson, R Meldrum


    Spreading depression (SD) is associated with large changes in extracellular ion concentrations and can be induced by impairing mechanisms of K(+) ion homeostasis. We tested activity dependence of SD in the locust model of ouabain-induced SD in the metathoracic ganglion. Wind activation of thoracic circuitry resulted in small increases of K(+) concentration that took 5-10 s to be cleared from the extracellular space. In the presence of the Na(+)/K(+)-ATPase inhibitor ouabain, wind stimulation every 30 s halved the latency to the first SD event and increased its duration. Wind stimulation was able to trigger the first event, suggesting that local activity could determine the origin of successive SD events. Perfusion with calcium-free saline blocked neural activity in the ganglion and prevented the occurrence of ouabain-induced SD. We conclude that ouabain-induced SD in the locust CNS is strongly dependent on the existing level of neural activity.

  20. Occupational risks for meningiomas of the CNS in Sweden.

    McLaughlin, J K; Thomas, T L; Stone, B J; Blot, W J; Malker, H S; Wiener, J A; Ericsson, J L; Malker, B K


    Using the Cancer-Environment Registry of Sweden, which links cancer incidence (1961 to 1979) with census information (1960) for all employed individuals in Sweden, a systematic, population-based assessment was made of the occurrence of meningiomas of the CNS according to industrial and occupational classifications. Statistically significant standardized incidence ratios (SIR) between 5 and 6 for meningioma were observed among glass, porcelain, or ceramic workers of both sexes. SIRs of similar magnitude were also found for men employed in the headwear fabrication and book publishing industries. Significantly elevated two- to three-fold risks were observed for men employed in health care, railroad and trolley construction, sheet and plate metal fabrication, and as moving equipment operators. Some of the findings of this descriptive survey may have arisen as a result of multiple comparisons, but several are consistent with earlier observations for brain cancer from other countries and deserve further study.

  1. Autoimmune control of lesion growth in CNS with minimal damage

    Mathankumar, R.; Mohan, T. R. Krishna


    Lesions in central nervous system (CNS) and their growth leads to debilitating diseases like Multiple Sclerosis (MS), Alzheimer's etc. We developed a model earlier [1, 2] which shows how the lesion growth can be arrested through a beneficial auto-immune mechanism. We compared some of the dynamical patterns in the model with different facets of MS. The success of the approach depends on a set of control parameters and their phase space was shown to have a smooth manifold separating the uncontrolled lesion growth region from the controlled. Here we show that an optimal set of parameter values exist in the model which minimizes system damage while, at once, achieving control of lesion growth.

  2. A map of taste neuron projections in the Drosophila CNS

    Jae Young Kwon; Anupama Dahanukar; Linnea A Weiss; John R Carlson


    We provide a map of the projections of taste neurons in the CNS of Drosophila. Using a collection of 67 GAL4 drivers representing the entire repertoire of Gr taste receptors, we systematically map the projections of neurons expressing these drivers in the thoracico-abdominal ganglion and the suboesophageal ganglion (SOG). We define 9 categories of projections in the thoracico-abdominal ganglia and 10 categories in the SOG. The projection patterns are modular, and can be interpreted as combinations of discrete pattern elements. The elements can be interpreted in terms of the taste organ from which the projections originate, the structures from which they originate, and the quality of taste information that they represent. The extensive diversity in projection patterns provides an anatomical basis for functional diversity in responses elicited by different taste stimuli.

  3. Chronically CNS-injured adult sensory neurons gain regenerative competence upon a lesion of their peripheral axon.

    Ylera, Bhavna; Ertürk, Ali; Hellal, Farida; Nadrigny, Fabien; Hurtado, Andres; Tahirovic, Sabina; Oudega, Martin; Kirchhoff, Frank; Bradke, Frank


    Several experimental manipulations result in axonal regeneration in the central nervous system (CNS) when applied before or at the time of injury but not when initiated after a delay, which would be clinically more relevant. As centrally injured neurons show signs of atrophy and degeneration, it raises the question whether chronically injured neurons are able to regenerate. To address this question, we used adult rodent primary sensory neurons that regenerate their central axon when their peripheral axon is cut (called conditioning) beforehand but not afterwards. We found that primary sensory neurons express regeneration-associated genes and efficiently regrow their axon in cell culture two months after a central lesion upon conditioning. Moreover, conditioning enables central axons to regenerate through a fresh lesion independent of a previous central lesion. Using in vivo imaging we demonstrated that conditioned neurons rapidly regrow their axons through a fresh central lesion. Finally, when single sensory axons were cut with a two-photon laser, they robustly regenerate within days after attaining growth competence through conditioning. We conclude that sensory neurons can acquire the intrinsic potential to regenerate their axons months after a CNS lesion, which they implement in the absence of traumatic tissue.

  4. Lidocaine-induced CNS toxicity--a case report.

    Chiang, Y Y; Tseng, K F; Lih, Y W; Tsai, T C; Liu, C T; Leung, H K


    Lidocaine is the first local anesthetic of the amide type to be introduced to clinical practice. It is a versatile drug and in anesthesia, is the most commonly used local anesthetic because of its aptness of potency, rapid onset, moderate duration of action and topical activity. It is relatively safe and useful in many other clinical settings. Unfortunately, systemic intoxication and psychotic reaction associated with its use often occur because of its popularity and wider safety margin, for which guide in use is often ignored and overdose becomes commonplace. Moreover, due to its universality in use seldom reports have recently dealt with lidocaine, particularly regarding its toxic reaction. Here, we present a case of lidocaine intoxication occurring during circumcision for a reviewal of the problem. A healthy young male, weighing 65 kg, underwent circumcision for phimosis under penile block with 2% lidocaine which totaled 600 mg. Twenty minutes after injection the patient developed headache, tinnitus, visual and auditory disturbances. Muscle twitching over the mouth angles, trismus and rigidity of extremities were also noted. Later in the course he became restless, agitative, hallucinative, talkative, and verbose with repetitious words. The whole course of the disorder lasted about 5 h. It was believed that lidocaine-induced CNS intoxication, manifested by psychotic reaction broke out. Treatment with thiopental was not very impressive. Also, we took this opportunity to discuss and review the toxic reaction associated with the use of lidocaine, its risk factors, mechanism, treatment and prevention. The complicated associations of lidocaine-induced CNS toxic reaction with central control of behavior and the neurotransmitter systems (adrenergic, dopaminergic and serotonin) were also touched.

  5. Evolution of the CNS myelin gene regulatory program.

    Li, Huiliang; Richardson, William D


    Myelin is a specialized subcellular structure that evolved uniquely in vertebrates. A myelinated axon conducts action potentials many times faster than an unmyelinated axon of the same diameter; for the same conduction speed, the unmyelinated axon would need a much larger diameter and volume than its myelinated counterpart. Hence myelin speeds information transfer and saves space, allowing the evolution of a powerful yet portable brain. Myelination in the central nervous system (CNS) is controlled by a gene regulatory program that features a number of master transcriptional regulators including Olig1, Olig2 and Myrf. Olig family genes evolved from a single ancestral gene in non-chordates. Olig2, which executes multiple functions with regard to oligodendrocyte identity and development in vertebrates, might have evolved functional versatility through post-translational modification, especially phosphorylation, as illustrated by its evolutionarily conserved serine/threonine phospho-acceptor sites and its accumulation of serine residues during more recent stages of vertebrate evolution. Olig1, derived from a duplicated copy of Olig2 in early bony fish, is involved in oligodendrocyte development and is critical to remyelination in bony vertebrates, but is lost in birds. The origin of Myrf orthologs might be the result of DNA integration between an invading phage or bacterium and an early protist, producing a fusion protein capable of self-cleavage and DNA binding. Myrf seems to have adopted new functions in early vertebrates - initiation of the CNS myelination program as well as the maintenance of mature oligodendrocyte identity and myelin structure - by developing new ways to interact with DNA motifs specific to myelin genes. This article is part of a Special Issue entitled SI: Myelin Evolution.

  6. The Gut-Brain Axis, BDNF, NMDA and CNS Disorders.

    Maqsood, Raeesah; Stone, Trevor W


    Gastro-intestinal (GI) microbiota and the 'gut-brain axis' are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-D-aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of other psychopathologies including neurodegenerative disorders, depression and dementias. An analysis of the routes and mechanisms by which the GI microbiota contribute to the pathophysiology of BDNF-induced NMDAR dysfunction could yield new insights relevant to developing novel therapeutics for schizophrenia and related disorders. In the absence of GI microbes, central BDNF levels are reduced and this inhibits the maintenance of NMDAR production. A reduction of NMDAR input onto GABA inhibitory interneurons causes disinhibition of glutamatergic output which disrupts the central signal-to-noise ratio and leads to aberrant synaptic behaviour and cognitive deficits. Gut microbiota can modulate BDNF function in the CNS, via changes in neurotransmitter function by affecting modulatory mechanisms such as the kynurenine pathway, or by changes in the availability and actions of short chain fatty acids (SCFAs) in the brain. Interrupting these cycles by inducing changes in the gut microbiota using probiotics, prebiotics or antimicrobial drugs has been found promising as a preventative or therapeutic measure to counteract behavioural deficits and these may be useful to supplement the actions of drugs in the treatment of CNS disorders.

  7. Cediranib, an Oral Inhibitor of Vascular Endothelial Growth Factor Receptor Kinases, Is an Active Drug in Recurrent Epithelial Ovarian, Fallopian Tube, and Peritoneal Cancer

    Matulonis, Ursula A.; Berlin, Suzanne; Ivy, Percy; Tyburski, Karin; Krasner, Carolyn; Zarwan, Corrine; Berkenblit, Anna; Campos, Susana; Horowitz, Neil; Cannistra, Stephen A.; Lee, Hang; Lee, Julie; Roche, Maria; Hill, Margaret; Whalen, Christin; Sullivan, Laura; Tran, Chau; Humphreys, Benjamin D.; Penson, Richard T.


    Purpose Angiogenesis is important for epithelial ovarian cancer (EOC) growth, and blocking angiogenesis can lead to EOC regression. Cediranib is an oral tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR) -1, VEGFR-2, VEGFR-3, and c-kit. Patients and Methods We conducted a phase II study of cediranib for recurrent EOC or peritoneal or fallopian tube cancer; cediranib was administered as a daily oral dose, and the original dose was 45 mg daily. Because of toxicities observed in the first 11 patients, the dose was lowered to 30 mg. Eligibility included ≤ two lines of chemotherapy for recurrence. End points included response rate (via Response Evaluation Criteria in Solid Tumors [RECIST] or modified Gynecological Cancer Intergroup CA-125), toxicity, progression-free survival (PFS), and overall survival (OS). Results Forty-seven patients were enrolled; 46 were treated. Clinical benefit rate (defined as complete response [CR] or partial response [PR], stable disease [SD] > 16 weeks, or CA-125 nonprogression > 16 weeks), which was the primary end point, was 30%; eight patients (17%; 95% CI, 7.6% to 30.8%) had a PR, six patients (13%; 95% CI, 4.8% to 25.7%) had SD, and there were no CRs. Eleven patients (23%) were removed from study because of toxicities before two cycles. Grade 3 toxicities (> 20% of patients) included hypertension (46%), fatigue (24%), and diarrhea (13%). Grade 2 hypothyroidism occurred in 43% of patients. Grade 4 toxicities included CNS hemorrhage (n = 1), hypertriglyceridemia/hypercholesterolemia/elevated lipase (n = 1), and dehydration/elevated creatinine (n = 1). No bowel perforations or fistulas occurred. Median PFS was 5.2 months, and median OS has not been reached; median follow-up time is 10.7 months. Conclusion Cediranib has activity in recurrent EOC, tubal cancer, and peritoneal cancer with predictable toxicities observed with other TKIs. PMID:19826113

  8. Screening for psychiatric comorbidity in children with recurrent headache or recurrent abdominal pain.

    Machnes-Maayan, Ditti; Elazar, Maya; Apter, Alan; Zeharia, Avraham; Krispin, Orit; Eidlitz-Markus, Tal


    Recurrent pain symptoms in children are associated with psychiatric comorbidities that could complicate treatment. We investigated the prevalence of psychiatric comorbidity in children with recurrent headache or recurrent abdominal pain and evaluated the screening potential of the Strength and Difficulties Questionnaire compared with the Development and Well-Being Assessment (DAWBA). Eighty-three outpatients aged 5-17 years attending a tertiary medical center for a primary diagnosis of migraine (n = 32), tension-type headache (n = 32), or recurrent abdominal pain (n = 19), and 33 healthy matched controls completed the brief self-reporting Strength and Difficulties Questionnaire followed by the Development and Well-Being Assessment. Findings were compared among groups and between instruments. The pain groups were characterized by a significantly higher number of Development and Well-Being Assessment diagnoses (range 0-11) than controls and a significantly greater prevalence (by category) of Development and Well-Being Assessment diagnoses (P headache groups than the controls (P Children referred to specialized outpatient pediatric units for evaluation of recurrent pain are at high risk of psychopathology. The Strength and Difficulties Questionnaire may serve as a rapid cost-effective tool for initial screening of these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Hormone therapy for patients with advanced or recurrent endometrial cancer.

    Lee, Wen-Ling; Yen, Ming-Shyen; Chao, Kuan-Chong; Yuan, Chiou-Chung; Ng, Heung-Tat; Chao, Hsiang-Tai; Lee, Fa-Kung; Wang, Peng-Hui


    The "gold standard" treatment for endometrial cancer is completely staged surgery, followed by radiation or chemotherapy, based on the final pathological surgical stage and requirements. In the primary treatment of endometrial cancers, hormones are rarely taken into consideration after primary surgery. Primary treatment with hormones to preserve fertility in younger women with endometrial cancer is an attractive option, and many successful cases have been reported, although the majority of them finally received definite therapy, including total hysterectomy. The role of hormone therapy is often delayed in recurrent disease; response rates to progestins and tamoxifen or aromatase inhibitors in advanced/recurrent endometrial cancers are approximately 15-20% and nearly ≤ 10%, respectively. This review is focused on updated information and recent knowledge on the use of hormones in the management of women with advanced or recurrent endometrial cancers.

  10. Direct inguinal hernias and anterior surgical approach are risk factors for female inguinal hernia recurrences

    Burcharth, Jakob; Andresen, Kristoffer; Pommergaard, Hans-Christian


    ), indirect inguinal hernia (IIH), combination hernia), the hernia type at the recurrent procedure (DIH, IIH, combination hernia, femoral hernia), anesthesia type, and time from primary procedure to reoperation were registered. RESULTS: A total of 5,893 females with primary elective inguinal hernia operation...... on in the study period (61 % IIH, 37 % DIH, 2 % combined hernias) were included with a median follow-up time of 72 months (range 0 to 169). A total of 305 operations for suspected recurrences were registered (61 % inguinal recurrences, 38 % femoral recurrences, 1 % no hernias), which corresponded to an overall...... reoperation rate of 5.2 %. All femoral recurrences occurred after a previous open anterior operation. The crude reoperation rate after primary DIH operation was 11.0 %, 3.0 % after primary IIH operation and 0.007 % after combined hernia operation (p 

  11. Multiscale recurrence quantification analysis of order recurrence plots

    Xu, Mengjia; Shang, Pengjian; Lin, Aijing


    In this paper, we propose a new method of multiscale recurrence quantification analysis (MSRQA) to analyze the structure of order recurrence plots. The MSRQA is based on order patterns over a range of time scales. Compared with conventional recurrence quantification analysis (RQA), the MSRQA can show richer and more recognizable information on the local characteristics of diverse systems which successfully describes their recurrence properties. Both synthetic series and stock market indexes exhibit their properties of recurrence at large time scales that quite differ from those at a single time scale. Some systems present more accurate recurrence patterns under large time scales. It demonstrates that the new approach is effective for distinguishing three similar stock market systems and showing some inherent differences.

  12. Recurrent Pregnancy Loss

    Véronique Piroux


    Full Text Available Antiphospholipid antibodies (APA are associated with thrombosis, thrombocytopenia and fetal loss but they occur in a variety of diseases. Despite many efforts, a correlation between the specificity of particular subgroups of APA and particular clinical situations remains to be established. The antigens at the origin of APA remain to be identified. We discuss here the possible links between cell apoptosis or necrosis, leading to plasma membrane alterations, and the occurrence of APA in response to sustained stimulation. The pathogenic potential of APA is also considered with respect to recurrent pregnancy loss.

  13. Recurrent Miller Fisher syndrome.

    Madhavan, S; Geetha; Bhargavan, P V


    Miller Fisher syndrome (MFS) is a variant of Guillan Barre syndrome characterized by the triad of ophthalmoplegia, ataxia and areflexia. Recurrences are exceptional with Miller Fisher syndrome. We are reporting a case with two episodes of MFS within two years. Initially he presented with partial ophthalmoplegia, ataxia. Second episode was characterized by full-blown presentation characterized by ataxia, areflexia and ophthalmoplegia. CSF analysis was typical during both episodes. Nerve conduction velocity study was fairly within normal limits. MRI of brain was within normal limits. He responded to symptomatic measures initially, then to steroids in the second episode. We are reporting the case due to its rarity.

  14. Recurrence Relations and Determinants

    Janjic, Milan


    We examine relationships between two minors of order n of some matrices of n rows and n+r columns. This is done through a class of determinants, here called $n$-determinants, the investigation of which is our objective. We prove that 1-determinants are the upper Hessenberg determinants. In particular, we state several 1-determinants each of which equals a Fibonacci number. We also derive relationships among terms of sequences defined by the same recurrence equation independently of the initial conditions. A result generalizing the formula for the product of two determinants is obtained. Finally, we prove that the Schur functions may be expressed as $n$-determinants.

  15. Equine recurrent uveitis: Human and equine perspectives.

    Malalana, Fernando; Stylianides, Amira; McGowan, Catherine


    Equine recurrent uveitis (ERU) is a spontaneous disease characterised by repeated episodes of intraocular inflammation. The epidemiology of ERU has not been fully elucidated, but the condition appears to be much more common in horses than is recurrent uveitis in humans, especially in certain breeds and geographical regions. Both humans and horses show a similarly altered immune response and a marked autoimmune response as the primary disease pathophysiology. However, an inciting cause is not always clear. Potential inciting factors in horses include microbial agents such as Leptospira spp. Microbial factors and genetic predisposition to the disease may provide clues as to why the horse appears so susceptible to this disease. The aim of this review is to discuss the immunology and genetics of ERU, compare the disease in horses with autoimmune anterior uveitis in humans, and discuss potential reasons for the increased prevalence in the horse.

  16. Endogenous GLP1 and GLP1 analogue alter CNS responses to palatable food consumption

    ten Kulve, Jennifer S.; Veltman, Dick J.; van Bloemendaal, Liselotte; Groot, Paul F. C.; Ruhe, Henricus G.; Barkhof, Frederik; Diamant, Michaela; Ijzerman, Richard G.


    Glucagon-like peptide-1 (GLP1) affects appetite, supposedly mediated via the central nervous system (CNS). In this study, we investigate whether modulation of CNS responses to palatable food consumption may be a mechanism by which GLP1 contributes to the central regulation of feeding. Using function

  17. Endogenous GLP1 and GLP1 analogue alter CNS responses to palatable food consumption

    ten Kulve, Jennifer S.; Veltman, Dick J.; van Bloemendaal, Liselotte; Groot, Paul F. C.; Ruhe, Henricus G.; Barkhof, Frederik; Diamant, Michaela; Ijzerman, Richard G.


    Glucagon-like peptide-1 (GLP1) affects appetite, supposedly mediated via the central nervous system (CNS). In this study, we investigate whether modulation of CNS responses to palatable food consumption may be a mechanism by which GLP1 contributes to the central regulation of feeding. Using function

  18. Exclusion of integrins from CNS axons is regulated by Arf6 activation and the AIS

    Franssen, Elske H P; Zhao, Rong-Rong; Koseki, Hiroaki; Kanamarlapudi, Venkateswarlu; Hoogenraad, Casper C; Eva, Richard; Fawcett, James W


    Integrins are adhesion and survival molecules involved in axon growth during CNS development, as well as axon regeneration after injury in the peripheral nervous system (PNS). Adult CNS axons do not regenerate after injury, partly due to a low intrinsic growth capacity. We have previously studied

  19. [Recurrence of upper aerodigestive tract tumors].

    Martin, Laurent; Zoubir, Mustapha; Le Tourneau, Christophe


    Recurrences of tumours of the upper aerodigestive tract are frequent despite the improvement of the primary treatment and they limit the rate of survival long-term. They occur in patients with multiple co-morbidities, often associated with sequelae or side effects of earlier treatments. The salvage treatment will add a cumulative toxicity and therapeutic options are limited. The choice will go from curator to palliative treatment. The report benefit-risk must be assessed in each case depending on the terrain and prognostic factors that have been identified, such as performance status, the time between initial disease and the recurrence, the site and the stratification of the recurrence. In operable non-metastatic recurrence surgery remains the treatment of choice. Multimodal treatment involving surgery, radiation therapy and chemotherapy in this context is being evaluated. Non-operable tumors have long been considered only in a palliative context. The evaluation of detailed irradiation as bifractionnated radiotherapy combined with chemotherapy helped establish protocols allowing long-term survivals and consider these treatments as potentially curators. However, the toxicity of these treatments is important. That is why the technical innovations of the radiation and the development of new chemotherapeutic agents today offer opportunities remaining to assess. The use of irradiation targeted by intensity-modulated radiation therapy (IMRT), and stereotactic radiotherapy by decreasing the irradiated volume should decrease the toxicity. Generally better tolerated than conventional chemotherapy agents, targeted therapies also took their places associated with radiotherapy in the treatment of these patients already treated. Cetuximab was the first agent obtaining an indication. Other agents are being evaluated in metastatic recurrent tumors, including exploring the possibilities of radiopotentialisation nanoparticles and the inhibitors of apoptosis proteins.

  20. Equine recurrent uveitis: the viewpoint from the USA.

    Gilger, B C


    Equine recurrent uveitis (ERU) is a common disease in horses in the USA. There have been many advances in the treatment of ERU; however, frequent misdiagnosis of ERU occurs in cases of primary corneal or uveal disease. It is critical to remember that primary uveitis (i.e. one bout of inflammation) is a different disease to ERU, which is an immune mediated recurrent uveitis. Standard symptomatic anti-inflammatory therapy is effective to control most cases of ERU; however, some horses require advanced therapy, such as placement of drug delivery devices or removal of the vitreous, when they fail to respond to the standard therapy.

  1. Photodynamic therapy for recurrent respiratory papillomatosis.

    Lieder, Anja; Khan, Muhammad K; Lippert, Burkard M


    Recurrent respiratory papillomatosis (RRP) is a benign condition of the mucosa of the upper aerodigestive tract. It is characterised by recurrent papillomatous lesions and is associated with human papillomavirus (HPV). Frequent recurrence and rapid papilloma growth are common and in part responsible for the onset of potentially life-threatening symptoms. Most patients afflicted by the condition will require repeated surgical treatments to maintain their airway, and these may result in scarring and voice problems. Photodynamic therapy introduces a light-sensitising agent, which is administered either orally or by injection. This substance (called a photo-sensitiser) is selectively retained in hyperplastic and neoplastic tissue, including papilloma. It is then activated by light of a specific wavelength and may be used as a sole or adjuvant treatment for RRP. To assess the effects of photodynamic therapy in the management of recurrent respiratory papillomatosis (RRP) in children and adults. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 27 January 2014. Randomised controlled trials utilising photodynamic therapy as sole or adjuvant therapy in participants of any age with proven RRP versus control intervention. Primary outcome measures were symptom improvement (respiratory distress/dyspnoea and voice quality), quality of life improvement and recurrence-free interval. Secondary outcomes included reduction in the frequency of surgical intervention, reduction in disease volume and adverse effects of treatment.   We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible and results are presented descriptively. We included one trial with a total of 23

  2. Recurrent correlation associative memories.

    Chiueh, T D; Goodman, R M


    A model for a class of high-capacity associative memories is presented. Since they are based on two-layer recurrent neural networks and their operations depend on the correlation measure, these associative memories are called recurrent correlation associative memories (RCAMs). The RCAMs are shown to be asymptotically stable in both synchronous and asynchronous (sequential) update modes as long as their weighting functions are continuous and monotone nondecreasing. In particular, a high-capacity RCAM named the exponential correlation associative memory (ECAM) is proposed. The asymptotic storage capacity of the ECAM scales exponentially with the length of memory patterns, and it meets the ultimate upper bound for the capacity of associative memories. The asymptotic storage capacity of the ECAM with limited dynamic range in its exponentiation nodes is found to be proportional to that dynamic range. Design and fabrication of a 3-mm CMOS ECAM chip is reported. The prototype chip can store 32 24-bit memory patterns, and its speed is higher than one associative recall operation every 3 mus. An application of the ECAM chip to vector quantization is also described.

  3. Recurrent Anion Gap Acidosis: An Unusual Presentation of X-Linked Adrenoleukodystrophy in a Five-year-old Male.

    Schwab, Joel; Pena, Loren; Sigman, Laura; Waggoner, Darrel


    We are presenting a five-year-old male with recurrent anion gap acidosis. During his last admission, it was detected that he had elevated VLCFA and the evaluation discovered that he had X-linked Adrenooleukodystrophy. He had the Addisonian only phenotype without any clinical or radiographic CNS findings. We were unable to find any other reports of this presentation of ALD. If the work-up of recurrent anion gap acidosis does not uncover an etiology, X-linked ALD should be considered in the differential diagnosis.

  4. [Treatment of recurrent posterior epistaxis].

    Bro, Søren Pauli; Bille, Jesper; Petersen, Kristian Bruun


    30% of the patients presenting with epistaxis at emergency wards and otorhinolaryngeal specialist departments have posterior bleeding. Traditional treatment with packing often leads to initial treatment failure, and many patients experience recurrent bleeding within the following month. Recurrent posterior epistaxis should be treated with local electrocautery or endoscopic ligation of the sphenopalatine artery to reduce patient discomfort, hospital stay, risk of treatment failure and recurrence.


    Francisco Capani


    of estradiol treatment we were able to revert some of these alterations using PI3K/Akt/GSK3. Overall these results demonstrate that synaptic dysfunction following PA might be produced by early changes in the actin organization and long-term misfolding and aggregation of proteins in the PSDs. Therefore, we hypothesize that the synaptic and neuronal cytoskeleton changes induced by PA in the rat CNS could lead to the cellular dysfunction and death in adult animals. Estradiol appears as a new therapeutic tool to slacken the damage induces by perinatal asphyxia on the CNS.

  6. Target identification for CNS diseases by transcriptional profiling.

    Altar, C Anthony; Vawter, Marquis P; Ginsberg, Stephen D


    Gene expression changes in neuropsychiatric and neurodegenerative disorders, and gene responses to therapeutic drugs, provide new ways to identify central nervous system (CNS) targets for drug discovery. This review summarizes gene and pathway targets replicated in expression profiling of human postmortem brain, animal models, and cell culture studies. Analysis of isolated human neurons implicates targets for Alzheimer's disease and the cognitive decline associated with normal aging and mild cognitive impairment. In addition to tau, amyloid-beta precursor protein, and amyloid-beta peptides (Abeta), these targets include all three high-affinity neurotrophin receptors and the fibroblast growth factor (FGF) system, synapse markers, glutamate receptors (GluRs) and transporters, and dopamine (DA) receptors, particularly the D2 subtype. Gene-based candidates for Parkinson's disease (PD) include the ubiquitin-proteosome system, scavengers of reactive oxygen species, brain-derived neurotrophic factor (BDNF), its receptor, TrkB, and downstream target early growth response 1, Nurr-1, and signaling through protein kinase C and RAS pathways. Increasing variability and decreases in brain mRNA production from middle age to old age suggest that cognitive impairments during normal aging may be addressed by drugs that restore antioxidant, DNA repair, and synaptic functions including those of DA to levels of younger adults. Studies in schizophrenia identify robust decreases in genes for GABA function, including glutamic acid decarboxylase, HINT1, glutamate transport and GluRs, BDNF and TrkB, numerous 14-3-3 protein family members, and decreases in genes for CNS synaptic and metabolic functions, particularly glycolysis and ATP generation. Many of these metabolic genes are increased by insulin and muscarinic agonism, both of which are therapeutic in psychosis. Differential genomic signals are relatively sparse in bipolar disorder, but include deficiencies in the expression of 14

  7. Psychosocial adjustment to recurrent cancer.

    Mahon, S M; Cella, D F; Donovan, M I


    This descriptive study of the perceptions and needs of people with recurrent malignancies asks three questions: How do patients describe the meaning of a recurrence of cancer? Do individuals perceive the diagnosis of recurrence and the initial diagnosis of cancer differently? What are the key psychosocial problems associated with recurrent cancer? The theoretical framework was based on Lazarus and Folkman's theory of stress, appraisal, and coping. Subjects completed the Impact of Event Scale (IES), the Psychosocial Adjustment to Illness Scale--Self-Report (PAIS), and a semistructured qualitative interview. The interview elicited perceptions of the event of recurrence and differences between the diagnosis of recurrence and the initial diagnosis. The convenience sample included 40 patients diagnosed with recurrent cancer within the last 30 days. Many subjects (78%) reported that the recurrence was more upsetting than the initial diagnosis. Scores on both the IES and the PAIS were high when compared to normative samples of patients with cancer suggesting that this sample of patients experienced a lot of psychological distress as well as problems at home, work, and in their social lives. These concerns often were unknown to caregivers. Although more research is needed, the authors propose that, with more accurate assessment, more effective intervention could be implemented and the quality of life improved for patients with recurrent cancer.

  8. Epidemiology of recurrent venous thrombosis

    D.D. Ribeiro


    Full Text Available Venous thrombosis, including deep vein thrombosis and pulmonary embolism, is a common disease that frequently recurs. Recurrence can be prevented by anticoagulants, but this comes at the risk of bleeding. Therefore, assessment of the risk of recurrence is important to balance the risks and benefits of anticoagulant treatment. This review briefly outlines what is currently known about the epidemiology of recurrent venous thrombosis, and focuses in more detail on potential new risk factors for venous recurrence. The general implications of these findings in patient management are discussed.

  9. 糖链结构在呼吸道乳头状瘤病发病中作用机制的初步研究%Primary study on glycan structure in pathopoiesis mechanism of recurrent respiratory papillomatosis

    王军; 韩德民; 康宏伟; 马丽晶; 叶京英; 肖洋


    Objective To compare the molecular basis difference between recurrent respiratory papillomatosis (RRP) and vocal cord polyp,to analyze the expression of glycan structural genes,and to discuss the pathopoiesis mechanism of RRP.Methods The gene expressing profile between the 3 groups papilloma and the vocal cord polyp regarded as normal larynx epithelium were compared using mRNA parallel amplify and the human genome gene expressing microarray.Through cluster analysis,Gene Ontology function gene annotation and path way analysis,the relative gene of RRP and HPV infection were acquired.Results According to three microarrays results,total 567 expression changed genes related to HPV induce RRP were acquired.A serial change of glycan structure biosynthesis and degradation pathways was significant.The expression of dolichyl-phosphate mannosyltransferase polypeptide 1(DPM1),asparagine-linked glycosylation 1 homolog (ALG1),fucosyltransferase 8(FUT8)and α-mannesidase 1A (MAN1A)were regulated and β-hexosaminidase(HEXB),β1-galactosidase(GLB1),exostoses 1 (EXT1),fucosyltransferase(FUT) reduced expression and heparan sulfate 3-O-sulfotransferase 1(HS3ST3A1) increased expression.The two related enzymes of the glyeosphingolipids which is the main composed of the cell membrane,β-3-N-acetylglucosaminyhransferase 4 (B3GNT4) and UDP-glucose ceramide glucosyltransferase (UGCG) increase expression,HEXB and GLB1 reduced expression.Conclusions The alteration of the coding genes of glycan structure biosynthesis and degradation pathways were significantly and characteristically in pathopoiesis mechanism of RRP.This abnormality may be the beginning of tumor form HPV infection.%目的 比较复发性呼吸道乳头状瘤病(recurrent respiratory papillomatosis,RRP)与声带息肉糖链结构相关基因表达的差异,研究人乳头状瘤病毒(human papillomavims,HPV)致呼吸道乳头状瘤病的分子机制.方法 利用mRNA平行扩增和人全基因组芯片分析比较3组(6例样

  10. Postoperative oligo-recurrence of non-small-cell lung cancer: clinical features and survival†.

    Hishida, Tomoyuki; Yoshida, Junji; Aokage, Keiju; Nagai, Kanji; Tsuboi, Masahiro


    Postoperative recurrences of non-small-cell lung cancer (NSCLC) are usually disseminated and systemic. Recently, the concept of oligo-recurrence, which is theoretically curable by definitive local therapy (DLT), has been proposed in several cancers. The aim of this study was to clarify clinical features and outcomes of patients with postoperative oligo-recurrence of NSCLC. From 3275 patients with resected pathological stage IA-IIIB NSCLC between 1993 and 2011, a total of 768 patients who developed recurrence were included in this study. Oligo-recurrence was defined as 1-3 loco-regional or distant recurrent lesions restricted to a single organ. Other recurrences were classified as poly-recurrence. Second primary lung cancers and suspected lesions were excluded. DLT included surgery, stereotactic radiotherapy and radiotherapy with a 45 Gy or higher dose, performed with curative intent. Oligo-recurrence was identified in 162 (21%) patients, mainly as a solitary recurrence (n = 129, 80%) in regional lymph nodes, brain, lung, bone and adrenal gland, and the proportion of patients with oligo-recurrence increased gradually year by year. The patients with oligo-recurrence had more early-staged disease at initial surgery and a longer time to recurrence than those with poly-recurrence. The entire population of oligo-recurrence patients had better post-recurrence survival (PRS) than those with poly-recurrence (5-year PRS: 32.9 vs 9.9%, P recurrence, DLT was totally conducted in 105 (65%) patients as initial treatment. Multivariate analyses revealed that the initial DLT was associated with improved PRS [odds ratio (OR) 0.44; 95% confidence interval (CI) 0.29-0.68]. The recurrence location and initial pathological stage did not affect PRS. The 5-year PRS and postoperative progression-free survival rates after DLT were 38.6 and 22.3%, respectively. Of the 10 long-term (≥5-year) progression-free survivors, 9 were those with a solitary recurrence. Initial DLT for oligo-recurrence

  11. Advances in recurrence and malignant transformation of sinonasal inverted papillomas

    Sun, Qingjia; An, Lifeng; Zheng, Jun; Zhu, Dongdong


    Sinonasal inverted papilloma (SIP) is a benign tumor of the nasal cavity and sinus. SIP is characterized by aggressive malignant transformation and a high rate of recurrence. Inadequate removal of the tumor during surgery is one of the most significant contributors to SIP recurrence. A growing body of evidence suggests that molecular alteration in SIP, including human papilloma virus infections, single nucleotide polymorphisms of key genes, deregulation of signaling pathways and immunological changes, may lead to SIP occurrence and malignant transformation. However, the extent to which these molecular mechanisms contribute to SIP pathology and transformation remains unclear due to limited research. Further studies are warranted to elucidate the primary dependent factors that contribute to SIP etiology. The present article reviewed risk factors of progression and recurrence of SIP, including outdoor and industrial occupational exposure, smoking, septal deviation, SIP location, recurrent cases, stage of SIP-associated squamous cell carcinoma and choice of surgical method. PMID:28599459




    Full Text Available ABSTRACT: Marjolin’s ulcer is a malignant tumour developing in a chronic skin lesion (burn scar, vaccination scar, non-healing wound etc.. Th e majority of cases reported are squamous cell carcinoma. Surgery remains the first treatment of choice (resection with 2cms. safety margin of healthy skin for primary squamous cell car cinoma Marjolin ulcers and 2.5cms. safety margin for recurrent cases. Recurrence after surge ry and regional lymph node metastasis are not uncommon (17% & 30% respectively.We presents a c ase report and literature review of Recurrent Marjolin’s Ulcer with regional Lymph Node Metastasis. Marjolin's ulcer should be considered as a significant post-burn complication; i t should be treated with full emphasis on adequate local clearance and regular follow up for m any years; if not treated adequately, it may lead to complicated recurrence.

  13. CNS fungal meningitis to the "Top of the basilar"

    Logan CS; Kirschner RC; Simonds GR


    Central nervous system(CNS) infections are a rare complication of epidural steroid injections and without strong clinical suspicion, fungal organisms may be overlooked among the long differential of causes of meningitis.Rare sequela of fungal meningitis is the development of stroke.To our knowledge, we present the first case of post epidural steroid injection(ESI) fungal meningitis leading toa basilar artery stroke, otherwise known as“top of the basilar” syndrome.We present a49-year-old female with a history ofESIs who presented to the emergency department with headache, neck stiffness, and abdominal pain.She was discharged after her labs and symptoms were deemed inconsistent with meningitis.She was eventually admitted and twelve days after her originalED visit, she was diagnosed with meningitis and started on anti-fungal treatment.She was discharged88 days later but was readmitted due to left sided weakness and mental status changes.She quickly lost motor and bulbar functions.AnMRA showed diminished distal flow through the basilar artery, suggesting near complete occlusion.Although appropriate long term anti-fungal treatment was started, the patient still succumbed to a rare vascular event.Physicians who are treating patients forESI meningitis should be aware of the potential for vasculitic and encephalitic complications.

  14. Stress preconditioning of spreading depression in the locust CNS.

    Corinne I Rodgers

    Full Text Available Cortical spreading depression (CSD is closely associated with important pathologies including stroke, seizures and migraine. The mechanisms underlying SD in its various forms are still incompletely understood. Here we describe SD-like events in an invertebrate model, the ventilatory central pattern generator (CPG of locusts. Using K(+ -sensitive microelectrodes, we measured extracellular K(+ concentration ([K(+](o in the metathoracic neuropile of the CPG while monitoring CPG output electromyographically from muscle 161 in the second abdominal segment to investigate the role K(+ in failure of neural circuit operation induced by various stressors. Failure of ventilation in response to different stressors (hyperthermia, anoxia, ATP depletion, Na(+/K(+ ATPase impairment, K(+ injection was associated with a disturbance of CNS ion homeostasis that shares the characteristics of CSD and SD-like events in vertebrates. Hyperthermic failure was preconditioned by prior heat shock (3 h, 45 degrees C and induced-thermotolerance was associated with an increase in the rate of clearance of extracellular K(+ that was not linked to changes in ATP levels or total Na(+/K(+ ATPase activity. Our findings suggest that SD-like events in locusts are adaptive to terminate neural network operation and conserve energy during stress and that they can be preconditioned by experience. We propose that they share mechanisms with CSD in mammals suggesting a common evolutionary origin.

  15. Electrophysiological CNS-processes related to associative learning in humans.

    Christoffersen, Gert R J; Schachtman, Todd R


    The neurophysiology of human associative memory has been studied with electroencephalographic techniques since the 1930s. This research has revealed that different types of electrophysiological processes in the human brain can be modified by conditioning: sensory evoked potentials, sensory induced gamma-band activity, periods of frequency-specific waves (alpha and beta waves, the sensorimotor rhythm and the mu-rhythm) and slow cortical potentials. Conditioning of these processes has been studied in experiments that either use operant conditioning or repeated contingent pairings of conditioned and unconditioned stimuli (classical conditioning). In operant conditioning, the appearance of a specific brain process is paired with an external stimulus (neurofeedback) and the feedback enables subjects to obtain varying degrees of control of the CNS-process. Such acquired self-regulation of brain activity has found practical uses for instance in the amelioration of epileptic seizures, Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). It has also provided communicative means of assistance for tetraplegic patients through the use of brain computer interfaces. Both extra and intracortically recorded signals have been coupled with contingent external feedback. It is the aim for this review to summarize essential results on all types of electromagnetic brain processes that have been modified by classical or operant conditioning. The results are organized according to type of conditioned EEG-process, type of conditioning, and sensory modalities of the conditioning stimuli.

  16. CNS Structural Anomalies in Iranian Children with Global Developmental Delay

    Gholam Reza ZAMANI


    Full Text Available How to Cite This Article: Zamani GH, Shervin Badv R, Niksirat A, Alizadeh H. CNS Structural Anomalies in Iranian Children with Global Developmental Delay. Iran J Child Neurol. 2013 Winter; 7 (1:25-28. ObjectiveCentral Nervous system (CNS malformations are one of the most important causes of global developmental delay (GDD in Children. About one percent of infants with GDD have an inherited metabolic disorder and 3-10 percent have a chromosomal disorder. This study aimed to survey the frequency of brain structural anomalies and their subtypes among the variety of etiologic factors in children with GDD in our patients.Materials & MethodsThis study used the results of neuroimaging studies [unenhanced brain Magnetic Resonance Imaging (MRI] of all children who had been referred for evaluation of GDD to outpatient Clinic of Pediatric neurology at Children’s Medical Center affiliated to Tehran University of Medical Science between September 2009 and September 2010.ResultsIn this study, unenhanced brain MRI was performed on 405 children, of which80 cases (20 percent had brain structural anomalies. In 8.7 percent of the cases, previous history of brain structural disorders existed in other children of the family and 20 percent of mothers had inadequate consumption of folate during pregnancy.ConclusionBased on the results of this study, unenhanced cranial MRI seems to be a fundamental part of evaluation in all children with GDD. Adequate folate consumption as prophylaxis as well as genetic counseling can be worthy for high-risk mothers who have previous history of CNS anomaly or miscarriage to avoid repeated CNS anomalies in their next pregnancies. References1. Fenichel M. Clinical Pediatric Neurology: A Signs and Symptoms Approach. 6th ed. Philadelphia: Saunders; 2009. p. 119-52.2. A guide to investigation of children with developmental delay in East Anglia 2005Available from:http://www. Williams J. Global developmental

  17. Increased fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) uptake in childhood CNS tumors is correlated with malignancy grade

    Borgwardt, Lise; Højgaard, Liselotte; Carstensen, Henrik;


    PURPOSE Positron emission tomography (PET) has been used in grading of CNS tumors in adults, whereas studies of children have been limited. PATIENTS AND METHODS Nineteen boys and 19 girls (median age, 8 years) with primary CNS tumors were studied prospectively by fluorine-18 2-fluoro-2-deoxy......-D-glucose (FDG) PET with (n = 16) or without (n = 22) H(2)(15)O-PET before therapy. Image processing included coregistration to magnetic resonance imaging (MRI) in all patients. The FDG uptake in tumors was semiquantitatively calculated by a region-of-interest-based tumor hotspot/brain index. Eight tumors.......89; P PET/MRI coregistration increased information on tumor characterization in 90...

  18. Recurrent pregnancy loss

    Egerup, P; Kolte, A M; Larsen, E C


    STUDY QUESTION: Is there a different prognostic impact for consecutive and non-consecutive early pregnancy losses in women with secondary recurrent pregnancy loss (RPL)? SUMMARY ANSWER: Only consecutive early pregnancy losses after the last birth have a statistically significant negative prognostic...... impact in women with secondary RPL. WHAT IS KNOWN ALREADY: The risk of a new pregnancy loss increases with the number of previous pregnancy losses in patients with RPL. Second trimester losses seem to exhibit a stronger negative impact than early losses. It is unknown whether the sequence of pregnancy...... losses plays a role for the prognosis in patients with a prior birth. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study of pregnancy outcome in patients with unexplained secondary RPL included in three previously published, Danish double-blinded placebo-controlled trials of intravenous...

  19. Recurrent vulvovaginal candidiasis.

    Sobel, Jack D


    Recurrent vulvovaginal candidiasis (RVVC) is a common cause of significant morbidity in women in all strata of society affecting millions of women worldwide. Previously, RVVC occurrence was limited by onset of menopause but the widespread use of hormone replacement therapy has extended the at-risk period. Candida albicans remains the dominant species responsible for RVVC, however optimal management of RVVC requires species determination and effective treatment measures are best if species-specific. Considerable progress has been made in understanding risk factors that determine susceptibility to RVVC, particularly genetic factors, as well as new insights into normal vaginal defense immune mechanisms and their aberrations in RVVC. While effective control of RVVC is achievable with the use of fluconazole maintenance suppressive therapy, cure of RVVC remains elusive especially in this era of fluconazole drug resistance. Vaccine development remains a critical challenge and need.

  20. Treatment of Recurrent Posttransplant Lymphoproliferative Disorder of the Central Nervous System with High-Dose Methotrexate

    Clare J. Twist


    Full Text Available Posttransplant lymphoproliferative disorder (PTLD is a frequent complication of intestinal transplantation and is associated with a poor prognosis. There is currently no consensus on optimal therapy. Recurrent PTLD involving the central nervous system (CNS represents a particularly difficult therapeutic challenge. We report the successful treatment of CNS PTLD in a pediatric patient after liver/small bowel transplantation. Initial immunosuppression (IS was with thymoglobulin, solucortef, tacrolimus, and mycophenolate mofetil. EBV viremia developed 8 weeks posttransplantation, and despite treatment with cytogam and valganciclovir the patient developed a polymorphic, CD20+, EBV+ PTLD with peripheral lymphadenopathy. Following treatment with rituximab, the lymphadenopathy resolved, but a new monomorphic CD20−, EBV+, lambda-restricted, plasmacytoid PTLD mesenteric mass emerged. Complete response of this PTLD was achieved with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP chemotherapy; however, 4 months off therapy he developed CNS PTLD (monomorphic CD20−, EBV+, lambda-restricted, plasmacytoid PTLD of the brain and spine. IS was discontinued and HD-MTX (2.5–5 gm/m2/dose followed by intrathecal HD-MTX (2 mg/dose ×2-3 days Q 7–10 days per cycle was administered Q 4–7 weeks. After 3 cycles of HD-MTX, the CSF was negative for malignant cells, MRI of head/spine showed near-complete response, and PET/CT was negative. The patient remains in complete remission now for 3.5 years after completion of systemic and intrathecal chemotherapy. Conclusion. HD-MTX is an effective therapy for CNS PTLD and recurrent PTLD that have failed rituximab and CHOP chemotherapy.