Expression profiles of the glucose-dependent insulinotropic peptide receptor and LHCGR in sporadic adrenocortical tumors

Glucose-dependent insulinotropic peptide receptor (GIPR) and LHCGR are G-protein-coupled receptors with a wide tissue expression pattern. Aberrant expression of these receptors has rarely been demonstrated in adult sporadic adrenocortical tumors with a lack of data on pediatric tumors. We quantified the GIPR and LHCGR expression in a large cohort of 55 patients (25 children and 30 adults) with functioning and non-functioning sporadic adrenocortical tumors. Thirty-eight tumors were classified as adenomas whereas 17 were carcinomas. GIPR, and LHCGR expression were analyzed by real-time PCR and normal human pancreatic and testicular tissue samples were used as positive controls. Mean expression values were determined by fold increase in comparison with a normal adrenal pool. GIPR mRNA levels were significantly higher in adrenocortical carcinomas than in adenomas from both pediatric and adult groups. LHCGR expression was similar in both carcinomas and adenomas from the pediatric group but significantly lower in carcinomas than in adenomas from the adult group (median 0.06 and 2.3 respectively, P<0.001). GIPR was detected by immunohistochemistry in both pediatric and adult tumors. Staining and real-time PCR results correlated positively only when GIPR in RN A levels were increased at least two-fold in comparison with normal adrenal expression levels. In Conclusion, GIPR overexpression was observed in pediatric and adult adrenocortical tumors and very low levels of LHCGR expression were found in all adult adrenocortical carcinomas.

Talc pleurodesis: Evidence of systemic Inflammatory response to small size talc particles

The mechanisms of the systemic response associated with talc-induced pleurodesis are poorly understood. The aim of this study was to assess the acute inflammatory response and migration of talc of small. size particles injected in the pleural space. Rabbits were injected intrapleurally with talc solution containing small. or mixed particles and blood and pleural fluid samples were collected after 6, 24 or 48 h and assayed for leukocytes, neutrophils, lactate dehydrogenase, IL-8, VEGF, and TGF-beta. The lungs, spleen, liver and kidneys were assessed to study deposit of talc particles. Both types of talc produced an acute serum inflammatory response, more pronounced in the small particles group. Pleural fluid IL-8 and VEGF levels were higher in the small particle talc group. Correlation between pleural VEFG and TGF-beta levels was observed for both groups. Although talc particles were demonstrated in the organs of both groups, they were more pronounced in the small talc group. In conclusion, intrapleural injection of talc of small size particles produced a more pronounced acute systemic response and a greater deposition in organs than talc of mixed particles. (C) 2008 Elsevier Ltd. All rights reserved.

EUS-guided percutaneous endoscopic gastrostomy for enteral feeding tube placement

Background: Patients without adequate abdominal-wall transillumination are at a high risk of developing complications after PEG. Objective: We evaluated the feasibility and utility of EUS to guide PEG in patients lacking abdominal-wall transillumination. Design: Single-center case series. Setting: Tertiary-referral center. Patients: Six patients who lacked adequate abdominal-wall transillumination and 2 patients with a large laparotomy scar deemed to be at high risk of developing complications after PEG. Interventions: Patients underwent EUS-guided PEG and deployment of a standard enteral feeding tube. Main Outcome Measurements: Technical success and complication rates. Results: PEG was Successful Under EUS guidance in 5 of 8 patients. Causes of failure included all inadequate EUS window because of a prior Billroth 1 gastrectomy in one and suspected bowel interposition in 2 patients. There were no complications. Limitations: A small number of patients, uncontrolled study, and short follow-up period. Conclusions: This technique may facilitate deployment of PEG in patients who lack adequate abdominal-wall transillumination.

Intracranial vascular lesions associated with small epidural hematomas

OBJECTIVE: We studied the angiographic findings in patients with small epidural hematomas and cranial fractures crossing over the trajectory of the middle meningeal artery and its branches. Additionally, the Occurrence of traumatic vascular lesions and their clinical relevance and treatment are discussed. METHODS: A consecutive analysis was performed for 24 patients who harbored small epidural hematomas in middle meningeal artery topography associated with cranial fractures. Computed tomographic scans and plain x-ray studies were used to diagnose linear cranial fractures. Patients with large epidural hematomas or associated traumatic lesions were excluded from the study. Selective ipsilateral external carotid angiograms were obtained, and an endovascular procedure was performed if any vascular injury was evidenced. RESULTS: In all patients with cranial fractures crossing over the middle meningeal artery and its branches, some kind of vascular lesion was seen. Two types of findings were noted: active extravasation of the contrast medium (71%) and pseudoaneurysms (29%). Early filling of diploic vessels was found in 8.3% of fractures concomitantly with active extravasation. Embolization was performed in all patients. No additional enlargement of the epidural hematoma was observed, and the postoperative period was uneventful. CONCLUSION: This study shows that pseudoaneurysms and active extravasation of contrast are common findings in this subset of patients. Although the natural history of these lesions is still poorly understood, additional investigation with ipsilateral external carotid angiography may be recommended, considering the potentially catastrophic consequences of late rupture.

Change in expression of miR-let7c, miR-100, and miR-218 from high grade localized prostate cancer to metastasis

Objective: MicroRNAs (miRNAs) are small noncoding regulatory RNAs (19-25 nucleotides) that play a major role in regulation of gene expression. They are responsible for the control of fundamental cellular processes that has been reported to be involved in human tumorigenesis. The characterization of miRNA profiles in human tumors is crucial for the understanding of carcinogenesis processes, finding of new tumor markers, and discovering of specific targets for the development of innovative therapies. The aim of this study is to find miRNAs involved in prostate cancer progression comparing the profile of miRNA expressed by localized high grade carcinoma and bone metastasis. Material and methods: Two groups of tumors where submitted to analyses. The first is characterized by 18 patients who underwent radical prostatectomy for treatment of localized high grade prostate carcinoma (PC) with mean Gleason score 8.6, all staged pT3. The second group is composed of 4 patients with metastatic, androgen-independent prostate carcinoma, and 2 PC cell lines. LNCaP derived from a metastatic PC to a lymph node, and another derived from an obstructive, androgen-independent PC (PcBRA1). Expression analysis of 14 miRNAs was carried out using quantitative RT-PCR. Results: miR-let7c, miR-100, and miR-218 were significantly overexpressed by all localized high GS, pT3 PC in comparison with metastatic carcinoma. (35.065 vs. 0.996 P < 0.001), (55.550 vs. 8.314, P = 0.010), and (33.549 vs. 2.748, P = 0.001), respectively. Conclusion: We hypothesize that miR-let7c, miR-100, and miR-218 may be involved in the process of metastasization of PC, and their role as controllers of the expression of RAS, c-myc, Laminin 5 beta 3, THAP2, SMARCA5, and BAZ2A should be matter of additional studies. (C) 2011 Elsevier Inc. All rights reserved.

Surgical management of glomus jugulare tumors: a proposal for approach selection based on tumor relationships with the facial nerve Clinical article

Object. The goal of this paper is to analyze the extension and relationships of glomus jugulare tumor with the temporal bone and the results of its surgical treatment aiming at preservation of the facial nerve. Based on the tumor extension and its relationships with the facial nerve, new criteria to be used in the selection of different surgical approaches are proposed. Methods. Between December 1997 and December 2007, 34 patients (22 female and 12 male) with glomus jugulare tumors were treated. Their mean age was 48 years. The mean follow-up was 52.5 months. Clinical findings included hearing loss in 88%, swallowing disturbance in 50%, and facial nerve palsy in 41%. Magnetic resonance imaging demonstrated a mass in the jugular foramen in all cases, a mass in the middle ear in 97%, a cervical mass in 85%, and an intradural mass in 41%. The tumor was supplied by the external carotid artery in all cases, the internal carotid artery in 44%, and the vertebral artery in 32%. Preoperative embolization was performed in 15 cases. The approach was tailored to each patient, and 4 types of approaches were designed. The infralabyrinthine retrofacial approach (Type A) was used in 32.5%; infralabyrinthine pre- and retrofacial approach without occlusion of the external acoustic meatus (Type B) in 20.5%; infralabyrinthine pre- and retrofacial approach with occlusion of the external acoustic meatus (Type C) in 41 W. and the infralabyrinthine approach with transposition of the facial nerve and removal of the middle ear structures (Type D) in 6% of the patients. Results. Radical removal was achieved in 91% of the cases and partial removal in 9%. Among 20 patients without preoperative facial nerve dysfunction, the nerve was kept in anatomical position in 19 (95%), and facial nerve function was normal during the immediate postoperative period in 17 (85%). Six patients (17.6%) had a new lower cranial nerve deficit, but recovery of swallowing function was adequate in all cases. Voice disturbance remained in all 6 cases. Cerebrospinal fluid leakage occurred in 6 patients (17.6%), with no need for reoperation in any of them. One patient died in the postoperative period due to pulmonary complications. The global recovery, based on the Karnofsky Performance Scale (KPS), was 100% in 15% of the patients, 90% in 45%, 80% in 33%, and 70% in 6%. Conclusions. Radical removal of glomus jugulare tumor can be achieved without anterior transposition of the facial nerve. The extension of dissection, however, should be tailored to each case based on tumor blood supply, preoperative symptoms, and tumor extension. The operative field provided by the retrofacial infralabyrinthine approach, or the pre- and retrofacial approaches. with or without Closure of the external acoustic meatus, allows a wide exposure of the jugular foramen area. Global functional recovery based on the KPS is acceptable in 94% of the patients. (DOI: 10.3171/2008.10.JNS08612)

Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma

We used high-resolution SNP genotyping to identify regions of genomic gain and loss in the genomes of 212 medulloblastomas, malignant pediatric brain tumors. We found focal amplifications of 15 known oncogenes and focal deletions of 20 known tumor suppressor genes (TSG), most not previously implicated in medulloblastoma. Notably, we identified previously unknown amplifications and homozygous deletions, including recurrent, mutually exclusive, highly focal genetic events in genes targeting histone lysine methylation, particularly that of histone 3, lysine 9 (H3K9). Post-translational modification of histone proteins is critical for regulation of gene expression, can participate in determination of stem cell fates and has been implicated in carcinogenesis. Consistent with our genetic data, restoration of expression of genes controlling H3K9 methylation greatly diminishes proliferation of medulloblastoma in vitro. Copy number aberrations of genes with critical roles in writing, reading, removing and blocking the state of histone lysine methylation, particularly at H3K9, suggest that defective control of the histone code contributes to the pathogenesis of medulloblastoma.

Serum Vitamins in Adult Patients With Short Bowel Syndrome Receiving Intermittent Parenteral Nutrition

Background: Short bowel syndrome (SBS) occurs after massive intestinal resection, and parenteral nutrition (PN) therapy may be necessary even after a period of adaptation. The purpose of this study was to determine the vitamin status in adults with SBS receiving intermittent PN. Methods: The study was conducted on hospitalized adults with SBS who were receiving intermittent PN therapy (n = 8). Nine healthy volunteers, paired by age and sex, served as controls. Food ingestion, anthropometry, plasma folic acid, and vitamins B(12), C, A, D, E, and K were evaluated. Results: The levels of vitamins A, D, and B(12) in both groups were similar. SBS patients presented higher values of folic acid (21.3 +/- 4.4 vs 14.4 +/- 5.2, P = .01) and lower values of vitamin C (0.9 +/- 0.4 vs 1.2 +/- 0.3 mg/dL, P = .03), alpha-tocopherol (16.3 +/- 3.4 vs 24.1 +/-+/- 2.7 mu mol/L, P < .001), and phylloquinone (0.6 +/- 0.2 vs 1.0 +/- 0.5 nmol/L, P < .03). Eight-seven percent of patients had vitamin D deficiency, and all patients presented with serum vitamin E levels below reference values. Conclusions: Despite all efforts to offer all the nutrients mentioned above, SBS patients had lower serum levels of vitamins C, E, and K, similar to those observed in patients on home PN. These findings suggest that the administered vitamins were not sufficient for the intermittent PN scheme and that individual adjustments are needed depending on the patient`s vitamin status. (JPEN J Parenter Enteral Nutr. 2011;35:493-498)

Impact of depressive symptoms on visceral sensitivity among patients with different subtypes of irritable Bowel syndrome

The etiology of irritable bowel syndrome (IBS) is complex and multifaceted. Psychosocial factors play a role in such a process. Several reports suggest that IBS patients have increased psychopathology scores as compared with population controls. The influence of depressive symptoms on rectal sensitivity thresholds vary across different studies. The influence of predominant bowel habits on rectal sensitivity thresholds as determined by barostat-based investigations is not well established. The present report aimed to investigate the influence of depressive symptoms on rectal sensitivity in different subtypes of IBS patients (diarrhea/constipation-predominant vs. alternating subtypes). Depressive symptoms correlated well with first pain sensitivity threshold in alternating patients (n = 8; [rho] = -0.77; p = 0.02) but not in diarrhea/constipation predominant symptoms (n = 11; [rho] = -0.44; p = 0.27). These data suggest that depressive symptoms might impact pain thresholds differently according to the subtype of IBS.

Liver mitochondrial function in familial amyloidotic polyneuropathy

The objective of the present study was to analyze hepatic mitochondrial function in patients with familial amyloidotic polyneuropathy (FAP) undergoing cadaveric donor orthotopic liver transplantation. From February `2005 to May 2007, eight patients with FAP, ranging in age from 34 to 41 years and with Model for End-Stage Liver Disease scores ranging from 24 to 29. Underwent orthotopic transplantation using a liver from a deceased donor by the piggyback method. Immediately before beginning the recipient hepatectomy in a patient with FAP, a biopsy was obtained for analysis of mitochondrial function (FAP group). The control group consisted of 15 patients undergoing hepatic surgery to treat small tumors of the liver. Mitochondrial respiration was determined on the basis of oxygen consumption by energized mitochondria using a polarographic method. The membrane potential of the mitochondria was determined spectrofluorometrically. Data were analyzed statistically by the Mann-Whitney test, with the level of significance set at 5%. State 3 and 4 values, respiratory control ratio, and membrane potential were 47 +/- 8 versus 28 +/- 10 natoms O/min/mg protein (P <.05); 14 +/- 3 vs 17 +/- 7 nat.O/min/ mg.prot.mit. (P >.05); 3.6+/- .5 vs 1.7 +/- 0.7 (P <.05); and 135 +/- 5.2 vs 135 +/- 6 mV (P >.05) for control versus FAP patients, respectively, demonstrating a decreased energy status of the liver in FAP.

Silencing of HTLV-1 gag and env genes by small interfering RNAs in HEK 293 cells

Since the discovery of RNAi technology, several functional genomic and disease therapy studies have been conducted using this technique in the field of oncology and virology. RNAi-based antiviral therapies are being studied for the treatment of retroviruses such as HIV-1. These studies include the silencing of regulatory, infectivity and structural genes. The HTLV-1 structural genes are responsible for the synthesis of proteins involved in the entry, assembly and release of particles during viral infection. To examine the possibility of silencing HTLV-1 genes gag and env by RNA interference technology, these genes were cloned into reporter plasmids. These vectors expressed the target mRNAs fused to EGFP reporter genes. Three small interference RNAs (siRNAs) corresponding to gag and three corresponding to env were designed to analyze the effect of silencing by RNAi technology. The plasmids and siRNAs were co-transfected into HEK 293 cells. The results demonstrated that the expression of the HTLV-1 gag and env genes decreased significantly in vitro. Thus, siRNAs can be used to inhibit HTLV-1 structural genes in transformed cells, which could provide a tool for clarifying the roles of HTLV-1 structural genes, as well as a therapy for this infection. (C) 2011 Elsevier B.V. All rights reserved.