Percheron-like artery infarction after transsphenoidal surgery: illustrative case.

BACKGROUND: The transsphenoidal approach to the skull base has enjoyed increasing popularity for surgery of the sellar region avoiding brain retraction and causing few severe complications. While vitally important vessels in this region show a high degree of variability, some anatomical variants might be involved in characteristic complications. OBSERVATIONS: We present the case of a 40-year-old female patient with acromegaly due to a pituitary adenoma that was transsphenoidally operated. Postoperatively, the patient presented with bilateral unresponsive mydriasis, loss of consciousness and tetraparesis. An MRI showed well-circumscribed bilateral paramedian thalamic infarctions which indicated a rare Percheron-like artery. At 2-year follow-up examination the patient was dramatically improved but with a profound impact on her ability to interact with the world. LESSONS: The basilar artery or perforators might be injured during dissection of suprasellar lesions. This vascular territory is essential to interaction of the brain with the outside world. We conclude that we will approach future suprasellar adenomas strictly intracapsularly.

Seroepidemiological analysis and literature review of the prevalence of Epstein-Barr virus and herpesvirus infections in pediatric cases with non-Hodgkin lymphoma in Central Europe.

BACKGROUND: Epstein-Barr virus (EBV) is linked to a variety of malignancies; most endemic Burkitt lymphoma (BL) harbor EBV, whereas only a subset of the cases of sporadic BL is EBV positive. PROCEDURE: We retrospectively determined the herpesvirus seroprevalence at the time of diagnosis in pediatric non-Hodgkin lymphoma (NHL) patients enrolled in NHL-BFM (Berlin-Frankfurt-Muenster) studies. We accessed the seroepidemiological data from 1147 patients that became available during 1990-2007. We included the records from patients 6 months to 18 years of age with BL, T-cell lymphoblastic lymphoma (T-LBL), lymphoblastic precursor B-cell lymphoma (pB-LBL), diffuse large B-cell lymphoma (DLBCL), or anaplastic large cell lymphoma (ALCL). RESULTS: EBV seropositivity was significantly more frequent in patients with BL than in those with T-LBL. EBV was more prevalent in patients younger than 6 years of age and in patients with BL than in those with non-BL or T-LBL. Event-free survival was significantly lower in varicella-zoster-seronegative patients, but there was no indication of an association to complications due to varicella zoster infection. We found no associations between herpes simplex virus, varicella zoster virus, or human cytomegalovirus seroprevalence and the pediatric Central European NHL cases. CONCLUSION: Early EBV exposure may increase the risk of BL in Central Europe. A higher involvement of EBV in European BL than originally reported appears at least probable. Our data support the thesis that the distinction between endemic and sporadic BL is artificial and should be replaced by the differentiation between EBV-positive and EBV-negative BL.

Light sensitivity in a vertebrate mechanoreceptor?

Using immunohistochemistry and western blot analysis, we demonstrate that melanopsin is localised in cells around the central pore of lateral line neuromasts in the African clawed frog, Xenopus laevis. Since melanopsin is a known photoreceptor pigment with diverse functions in vertebrates, we suggest that the lateral line of Xenopus laevis, which is primarily a mechanoreceptor, might also be light sensitive. Potential functions of such photosensitivity are discussed, including its role in mediating locomotor responses following dermal illumination.

Determining EBV load: current best practice and future requirements.

EBV, a gammaherpesvirus and the pathogenic agent for infectious mononucleosis, is also associated with a broad spectrum of lymphoid and epithelial malignancies in immunocompetent and immunosuppressed individuals. EBV-DNA-load measurement by PCR has been shown to be a potential tool for the diagnosis of these diseases, a prognostic factor of their outcome and a successful method to monitor immunosuppressed patients. Since the end of 2011, there is an international WHO standard reference for EBV quantification available; however, many questions still remain; for instance about the optimal amplified region of the EBV genome, or the best-used specimen for EBV detection. Additionally, the optimal specimen and amplified region may vary in different malignancies. In this article, the authors review the different methods to measure EBV load, focus on the best-used specimen for the different EBV-associated malignancies and discuss future requirements and opportunities for EBV-load measurement.

Solid variant of aneurysmal bone cyst of the left parietal bone without preceding trauma.

INTRODUCTION: We report the case of a 17-year-old girl with an indolent, smooth swelling of the left cranial vault that had been developing for 2 months. Complete surgical excision was performed and the defect was closed using artificial bone cement. The integrity of the dura mater was conserved and the patient recovered without neurological deficit. Magnetic resonance imaging (MRI) controls 6 and 18 months after the operation did not find signs of recurrence. RESULTS: The lesion consisted of an elastic bone shell containing bony trabeculae with soft brown-greyish tissue and posthemorrhagic dark fluid. Histological assessment found CD68 positive multinucleated giant cells in a highly cellular fibroblastic matrix surrounding bony lamellar structures, without signs of inflammation or malignancy. Hyperparathyroidism was ruled out by normal serum values for parathyroid hormone, calcium, phosphate, and alkaline phosphatase. Histologically, first diagnosis was giant cell reparative granuloma and reference pathology disclosed aneurysmal bone cyst. CONCLUSIONS: The solid variant of aneurysmal bone cyst and the giant cell reparative granuloma can be histologically indistinguishable. Both lesions are only rarely encountered in cranial bones and most published cases affected the cranial base or the jaw, mainly in children or young adults. From a clinical point of view, classification into "outward" lesions (osteolysis of external parts of the vault with preservation of internal tabula) and "inward" lesions (intracranial multicystic lesions with raise of intracranial pressure) has been proposed. Three phases of development can be identified, and spontaneous involution has been described. Both entities are benign, but because in several cases an underlying malignant disease has been found, complete resection and regular follow-up by MRI are recommended.

Examining the origin of posttransplant lymphoproliferative disorder in a patient after a second allogeneic hematopoeitic stem cell transplantation for relapsed BCR-ABL positive acute lymphoblastic leukemia.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious complication because of the reactivation of the Epstein-Barr virus (EBV). Although after solid organ transplantation (SOT) EBV is typically of recipient origin, after hematopoietic stem cell transplantation (HSCT) donor-derived B cells are usually the source of the EBV-induced lymphoproliferation. OBSERVATION: We report a unique presentation of an EBV-associated PTLD in a 13-year-old boy who underwent 2 subsequent HSCTs from 2 different-sex donors for BCR-ABL-positive acute lymphoblastic leukemia (ALL) and relapses of leukemia, respectively. The PTLD tissue was analyzed for the origin of both B cells and T cells of the lesion. Chimerism analysis done with short tandem repeat systems (STR) showed no autologous signals; approximately 50% of the cells were from the first and second donors, respectively. XY-fluorescence in situ hybridization showed a B-cell PTLD originating from the first donor surrounded by T cells from the second donor. CONCLUSION: This case shows that EBV-infected B cells from a first donor can be the source of a PTLD after a second myeloablative HSCT from a different donor.

Infection of T lymphocytes in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children of non-Asian origin.

BACKGROUND: Epstein-Barr virus (EBV) is one of the most frequent triggers of hemophagocytic lymphohistiocytosis (HLH). EBV-associated HLH (EBV-HLH) and ectopic infection of T cells has been particularly described in patients from Far East Asia. PROCEDURE: In a cohort of 12 children with EBV-HLH treated in Germany, the EB viral load was detected by real-time polymerase chain reaction in plasma and peripheral blood mononuclear cells (PBMC). Virological and clinical data were analyzed retrospectively. RESULTS: Among the 12 mainly German patients, children with underlying immunodeficiencies as well as otherwise healthy individuals were affected. The clinical course ranged from a steroid-responding to a fatal disease despite intensive treatment. Increased EBV copy numbers in plasma and/or PBMC were found in all patients. Serial measurements reflected the course of the disease. Cell-type specific viral load was determined in seven patients and revealed EBV-infection of T cells in all of them. In contrast to the reported Asian patients a significant viral load was also found in B cells. CONCLUSIONS: T cell infection appears to be a typical feature of EBV-associated HLH irrespective of patients ethnic background and the clinical course. Evaluation of cell-type specific infection should be considered when targeted therapy is applied.

Selective internal radiotherapy with Yttrium-90 microspheres for hepatic metastatic neuroendocrine tumors: a prospective single center study.

BACKGROUND: To assess prospectively the safety and efficacy of Yttrium-90 microspheres in patients with unresectable liver metastases from neuroendocrine tumors. MATERIALS AND METHODS: Microspheres were administered via a temporarily placed hepatic catheter. Patients were monitored prospectively. All patients were followed with laboratory and imaging studies at regular intervals to determine response rates. Toxicity and quality of life scores were measured. RESULTS: Nine patients (7 female) with a mean age of 58.8 years were enrolled in this prospective trial. The mean tumor load was 58.8%. The estimated percentage shunting to the lungs on MAA scans was 5.04 +/- 2.4%. Visceral artery embolization of extrahepatic arteries before treatment was performed in 6 patients. The median dose of microspheres was 2.1 +/- 0.4 GBq. A total of 12 therapy sessions was performed. The mean follow-up was 21.7 months. Technical success was 100%. No major complications occurred. Survival rates were 100, 57 and 57% for 1, 2 and 3 years, respectively. Three months after SIRT therapy partial response (PR) was seen in 6 patients (66%). Calculated reduction of liver metastasis volume was 49%. In 3 patients (33%) stable disease was seen with a calculated tumor reduction of 13%. The estimated time to progression was 11.1 months. CONCLUSION: Radioembolization with (90)Y microspheres is safe and produces high response rates even with extensive tumor replacement for up to 1 year. Acute and late toxicity was very low. Further investigations compared with other local ablative techniques is warranted.

Ovarian tumor in a 12-year old female with severe hypothyroidism: A case of Van Wyk and Grumbach syndrome.

We report a 12-year-old female presenting with an abdominal tumor. Diagnostic workup revealed giant bilateral ovarian cysts, severe hypothyroidism as well as an elevation of CA 125. We refrained from ovariectomy, which would be necessary for a malignant tumor, in view of an evident Van Wyk and Grumbach syndrome. The patient promptly responded to L-thyroxine with complete regression of all symptoms. Hypothyroidism should be considered in the evaluation of ovarian cysts. Although the Van Wyk and Grumbach syndrome is rare, it is crucial to rule it out in order to avoid unnecessary ovarian surgery when thyroid replacement is completely sufficient.

Generation of pluripotent stem cells from adult human testis.

Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells.

DNA double-strand breaks after percutaneous transluminal angioplasty.

PURPOSE: To determine exemplarily the amount of DNA damage and the repair kinetics after interventional radiologic procedures by using visualization of foci of the phosphorylated form of the H2AX histone variant (gammaH2AX) to quantify DNA double-strand breaks (DSBs) at percutaneous transluminal angioplasty (PTA) of the lower limb arteries. MATERIALS AND METHODS: After local ethics committee approval and written informed consent were obtained, five patients (two women, three men; mean age, 64.4 years; age range, 45-76 years) scheduled for computed tomography (CT) and 20 patients (six women, 14 men; mean age, 68.5 years; age range, 53-85 years) scheduled for PTA of lower limb arteries were prospectively entered into the study. Blood samples were taken before the first exposure to ionizing radiation and 5 minutes, 1 hour, 6 hours, and 24 hours after the last exposure. Additional samples were taken from the irradiated limb (femoral vein) of three patients who underwent PTA--before the first radiation exposure, 5 and 10 minutes after the first exposure, and 5 minutes after the last exposure. Lymphocytes were isolated, fixed, and stained with anti-gammaH2AX antibody, and gammaH2AX focus yields were determined with fluorescence microscopy. Data were analyzed with linear regression and two-sample F tests. RESULTS: Mean increase in number of gammaH2AX foci after CT (7.78 per 1 Gy x cm) depended linearly on dose-length product (r = 0.997). Number of foci reached background levels within 24 hours. Mean numbers of gammaH2AX foci per cell increased by factors of 4.08-20.67 in blood samples taken 5 minutes after PTA compared with mean numbers of foci before PTA. Mean radiation dose increase, 6.56/(10 Gy x cm(2)), depended linearly on dose-area product (r = 0.993). Maximal focus yield in cells taken directly from the irradiated limb was higher than that in cells from the systemic circulation (by mean factor of 1.46). Data showed compromised DSB repair capacity after PTA (P < .05). Mean number of foci at 24 hours (0.07 focus per cell) was significantly higher than mean number of foci in cell background (0.04 focus per cell, P < .05). CONCLUSION: GammaH2AX focus formation can be used to determine in vivo induction of DNA DSBs after PTA. DSB repair capacity is compromised in patients who undergo PTA of lower limb arteries.

Sonographically guided venous puncture and fluoroscopically guided placement of tunneled, large-bore central venous catheters for bone marrow transplantation-high success rates and low complication rates.

BACKGROUND AND OBJECTIVE: Traditionally, large lumen, tunneled central venous catheters have been implanted by surgeons. We used a technique of sonographically guided jugular venous puncture and fluoroscopically guided catheter placement to achieve a high rate of technical success and to reduce complication rates. MATERIALS AND METHODS: Between June 2002 and December 2006, 186 Patients have been referred to the Radiology Department for 211 implantations of large-lumen, tunneled, central venous catheters. Insertions were performed under maximum sterile barrier in the angio suite using combined sonographic guidance for puncture of the internal jugular vein and fluoroscopy for placement of a triple lumen 12.5 F catheter (Hickman, BARD Murray Hill, NJ, USA). All interventions were performed under local anesthesia without need for anesthesiologic surveillance. Peri- and postinterventional complications were recorded using standardized international recommendations. RESULTS: Catheter implantation was technically successful in 207 of 211 cases (98.1%). Technical failure resulted in four patients due to chronic occlusions of the superior vena cava. No major complications were recorded. Four (1.9%) accidental arterial punctures occurred peri-interventionally; 24 (11.4%) early complications (bleeding, dysfunction, catheter rupture, and infection) and ten (4.7%) late complications (infection, dysfunction) were recorded. A clinically suspected catheter infection required catheter removal in 21 (10%) cases; 11 of 13 non-infectious catheter complications (bleeding, dysfunction, rupture) could be treated successfully by interventional-radiological treatment. CONCLUSION: Percutaneous implantation of large-lumen, tunneled, central venous catheters can be achieved with a high technical success rate and a low complication rate under combined sonographic and fluoroscopic guidance. In cases of mechanical complications, catheter rescue by interventional techniques is possible in the vast majority of cases.

CNS or bone marrow involvement as risk factors for poor survival in post-transplantation lymphoproliferative disorders in children after solid organ transplantation.

PURPOSE: To identify prognostic factors of survival in pediatric post-transplantation lymphoproliferative disorder (PTLD) after solid organ transplantation. PATIENTS AND METHODS: A multicenter, retrospective case analysis of 55 pediatric solid organ graft recipients (kidney, liver, heart/lung) developing PTLD were reported to the German Pediatric-PTLD registry. Patient charts were analyzed for tumor characteristics (histology, immunophenotypes, cytogenetics, Epstein-Barr virus [EBV] detection), stage, treatment, and outcome. Probability of overall and event-free survival was analyzed in defined subgroups using univariate and Cox regression analyses. RESULTS: PTLD was diagnosed at a median time of 29 months after organ transplantation, with a significantly shorter lag time in liver (0.83 years) versus heart or renal graft recipients (3.33 and 3.10 years, respectively; P = .001). The 5-year overall and event-free survival was 68% and 59%, respectively, with 59% of patients surviving 10 years. Stage IV disease with bone marrow and/or CNS involvement was associated independently with poor survival (P = .0005). No differences in outcome were observed between early- and late-onset PTLD, monomorphic or polymorphic PTLD, and EBV-positive or EBV-negative PTLD, respectively. Patients with Burkitt or Burkitt-like PTLD and c-myc translocations had short survival (< 1 year). CONCLUSION: Stage IV disease is an independent risk factor for poor survival in pediatric PTLD patients. Prospective multicenter trials are needed to delineate additional risk factors and to assess treatment approaches for pediatric PTLD.

Glucocorticoid adrenal steroids and glucocorticoid-inducible kinase isoforms in the regulation of GluR6 expression.

Generation of memory is enhanced during stress, an effect attributed to stimulation of neuronal learning by adrenal glucocorticoids. The glucocorticoid-dependent genes include the serum- and glucocorticoid-inducible kinase SGK1. SGK1 is activated through the phosphatidylinositol 3 kinase (PI3-kinase) pathway by growth factors such as insulin-like growth factor-1 (IGF1) or tumour growth factor beta (TGF-beta). Previously, a fourfold higher expression of SGK1 has been observed in fast-learning rats as compared with slow-learning rats. The mechanisms linking glucocorticoids or SGK1 with neuronal function have, however, remained elusive. We show here that treatment of mice with the glucocorticoid dexamethasone (238 microg day-1 for 8-20 days) enhances hippocampal expression of GluR6. Immunohistochemistry reveals significantly enhanced GluR6 protein abundance at neurones but not at astrocytes in mice. Immunohistochemistry and patch clamp on hippocampal neurones in primary culture reveal upregulation of GluR6 protein abundance and kainate-induced currents following treatment with dexamethasone (1 microm) and TGF-beta (1 microm). In Xenopus oocytes expressing rat GluR6, coexpression of SGK1 strongly increases glutamate-induced current at least partially by increasing the abundance of GluR6 protein in the plasma membrane. The related kinases SGK2 and SGK3 similarly stimulate GluR6, but are less effective than SGK1. The observations point to a novel mechanism regulating GluR6 which contributes to the regulation of neuronal function by glucocorticoids.

Cellular immunity to Epstein-Barr virus in liver transplant recipients treated with rituximab for post-transplant lymphoproliferative disease.

The evaluation of long-term cellular immunity to EBV in pediatric orthotopic liver transplant (OLT) recipients after treatment with the humanized anti-CD20 monoclonal antibody (Rituximab) has not yet been explored. At our institution, one child with EBV-related mononucleosis-like syndrome and five children with polymorphic-EBV-PTLD occurring 6-88 months after OLT were treated with Rituximab. Treatment was well tolerated. All children achieved complete remission. After Rituximab, B-lymphocytes were undetectable in the peripheral blood and EBV-load, monitored with real-time PCR, decreased to undetectable levels in all children from >4000 copies/microg DNA at diagnosis. Four to eight months after Rituximab, EBV-load increased (>4000 copies/microg DNA) in four children, and PTLD recurred in three. Their frequency of EBV-specific T-cell precursors, measured by Elispot analysis, remained lower than in healthy controls. Rituximab effectively induced regression of PTLD in OLT recipients. However, EBV-specific T-cell immunocompetence, which may be crucial for the long-term control of EBV-mediated proliferation, did not improve.

Pancreatic transplants: noninvasive evaluation with secretin-augmented mr pancreatography and MR perfusion measurements--preliminary results.

Feasibility of secretin-augmented magnetic resonance (MR) pancreatography and dynamic contrast material-enhanced MR measurements for evaluation of functional status of pancreatic allografts was determined by quantifying the excretion and perfusion of the grafts. Ten patients were included prospectively before pancreatic transplantation. Dynamic T2-weighted sequences after secretin stimulation and dynamic contrast-enhanced T1-weighted gradient-echo sequences were performed. Area under the curve and maximum signal intensity-to-time ratio were determined in selected regions of interest. Biochemical parameters, Doppler ultrasonography, and/or surgery were standards for final diagnosis. Patients with normal outcome (n = 7) produced 236 mL +/- 104 (standard deviation) of pancreatic juice, and patients with dysfunctional grafts (n = 3) produced 42 mL +/- 25. Area under the curve and maximum signal intensity-to-time ratio provided thresholds of 0.5 and 0.3, respectively, for distinction between functional and dysfunctional grafts. Secretin-augmented MR pancreatography combined with MR perfusion measurements may aid in differentiation between patients with and those without graft dysfunction.

Treatment of benign tracheal stenosis utilizing self-expanding nitinol stents.

We assessed the results of self-expanding metallic stent insertion into benign proximal tracheal stenosis in patients not appropriate or unfit for surgical repair. Proximal benign tracheal stenoses had occurred in 11 patients (7 men, 4 women, mean age 68.8 years) after long-time intubation (n = 6), tracheostomy (n = 4), or chondropathia (n = 1). Fourteen self-expanding nitinol stents were placed in the patients under general anesthesia with endoscopical and fluoroscopical guidance. Stent insertion was successful in all cases and led to immediate relief of the morphological and functional airway obstruction. No immediate complications were noted. During the mean follow-up period of 67.5 weeks we observed one recurrent dyspnea 3 months after implantation and granuloma formation at the stent insertion site in another patient. Both complications were successfully treated with additional stent insertion in one case and laser resection of granulomas in the other. Self-expanding nitinol stents should be considered for the treatment of benign proximal tracheal obstruction in selected patients for whom surgical repair is contraindicated.

Peripheral blood lymphocytes express recombination-activating genes 1 and 2 during Epstein-Barr virus-induced infectious mononucleosis.

Implicit in the persistence of Epstein-Barr virus (EBV) in B lymphocytes is the successful circumvention of ongoing cell selection for competence of B cell receptors (BCRs). Because the EBV infection of B cells in vitro induces enzymatic machinery that is responsible for secondary immunoglobulin gene rearrangement, we examined the expression of the recombination-activating genes (RAGs) in peripheral blood mononuclear cells (PBMCs) from 26 patients with infectious mononucleosis (IM). RAG1 and/or RAG2 RNA was detected in PBMCs from 42% of patients with IM but not from healthy control subjects. EBV may usurp the cellular mechanism that diversifies the BCR, to guarantee a level of survival signaling sufficient for its own persistence.

Prompt versus preemptive intervention for EBV lymphoproliferative disease.

Posttransplantation lymphoproliferative disorders (PTLDs) caused by uncontrolled expansion of Epstein-Barr virus (EBV)-infected B cells after hematopoietic stem cell transplantation (HSCT) can be predicted by an increase in EBV DNA in peripheral blood mononuclear cells. We used real-time quantitative polymerase chain reaction (RQ-PCR) analysis to determine whether frequent monitoring of EBV DNA to allow preemptive treatment is truly of value in patients after HSCT. More than 1300 samples from 85 recipients were analyzed. No patient with consistently low EBV DNA levels developed PTLD. Nine patients had a single episode with a high EBV load (more than 4000 EBV copies/microg peripheral blood mononuclear cell [PBMC] DNA), and 16 patients had high EBV loads detected on 2 or more occasions. Only 8 of these developed symptoms consistent with PTLD, and all were promptly and successfully treated with EBV-specific cytotoxic T cells or CD20 monoclonal antibody. Hence, quantitative measurement of EBV DNA may best be used to enable the prompt rather than the preemptive treatment of PTLD.