Long-term follow-up of children with extrahepatic portal vein obstruction: impact of an endoscopic sclerotherapy program on bleeding episodes, hepatic function, hypersplenism, and mortality

Background: Endoscopic sclerotherapy (ES) has been the standard treatment for children with idiopathic extrahepatic portal vein obstruction (EHPVO). Portosystemic shunts are indicated when variceal bleeding cannot be controlled by ES. Recently, mesenteric left portal vein bypass was indicated as a surgical intervention and preventative measure for hepatic dysfunction in children with long-term EHPVO. Nevertheless, there is a lack Of published data confirming the extent of hepatic dysfunction, hypersplenism, and physical development in children with long-term follow-up. Method: We retrospectively verified the long-term outcomes in 82 children with EHPVO treated with ES protocol, focusing on mortality, control of bleeding, hypersplenism, and consequent hepatic dysfunction. Results: Of the children, 56% were free from bleeding after the initiation of ES. The most frequent cause of rebleeding was gastric varices (30%). Four patients had recurrent bleeding from esophageal varices (4.6%). Four patients underwent surgery as a consequence of uncontrolled gastric varices. There were no deaths. Most patients showed good physical development. We observed a mild but statistically significant drop in factor V motion, as well as leukocyte and platelet count. Conclusion: Endoscopic sclerotherapy is an efficient treatment for children with EHPVO. The incidence of rebleeding is low, and there was no mortality. Children develop mild liver dysfunction and hypersplenism with long-term follow-up. Only a few patients manifest symptoms of hypersplenism, portal biliopathy, or liver dysfunction before adolescence. (C) 2009 Elsevier Inc. All rights reserved.

Early-Onset, Progressive, Frequent, Extensive, and Severe Bone Mineral and Renal Complications in Multiple Endocrine Neoplasia Type 1-Associated Primary Hyperparathyroidism

Differences in bone mineral density (BMD) patterns have been recently reported between multiple endocrine neoplasia type 1-related primary hyperparathyroidism (HPT/MEN1) and sporadic primary HPT However studies on the early and later outcomes of bone/renal complications in HPT/MEN1 are lacking In this cross sectional study performed in a tertiary academic hospital 36 patients cases with uncontrolled HPT from 8 unrelated MEN1 families underwent dual energy X ray absorptiometry (DXA) scanning of the proximal one third of the distal radius (1/3DR) femoral neck, total hip, and lumbar spine (LS) The mean age of the patients was 389 +/- 145 years Parathyroid hormone (PTH)/calcium values were mildly elevated despite an overall high percentage of bone demineralization (77 8%) In the younger group (<50 years of age) demineralization in the 1/3DR was more frequent more severe and occurred earlier (40% Z-score 1 81 +/- 0 26) The older group (>50 years of age) had a higher frequency of bone demineralization at all sites (p < 005) and a larger number of affected bone sites (p < 0001), and BMD was more severely compromised in the 1/3DR (p = 007) and LS (p= 002) BMD values were lower in symptomatic (88 9%) than in asymptomatic HPT patients (p < 006) Patients with long standing HPT (>10 years) and gastnnoma/HPT presented significantly lower 1/3DR BMD values Urolithiasis occurred earlier (<30 years) and more frequently (75%) and was associated with related renal comorbidities (50%) and renal insufficiency in the older group (33%) Bone mineral- and urolithiasis-related renal complications in HPT/MEN1 are early onset frequent extensive severe and progressive These data should be considered in the individualized clinical/surgical management of patients with MEN1 associated HPT (C) 2010 American Society for Bone and Mineral Research

Incidental Encoding Strategies Did Not Improve Contextual Memory in Parkinson`s Disease Patients

Background. This study investigated the performance of patients with idiopathic Parkinson`s disease (PD) without dementia for incidental recognition memory and the effect of encoding strategies on contextual memory. Methods. The authors studied 21 patients with PD (ages 60-85, 12 women; Hoehn and Yahr I-III, Activities of Daily Living 70%-100%) and 22 healthy controls (ages 60-84, 18 women). Participants completed the vocabulary subtest of the Wechsler Adult Intelligence Scale and the Wisconsin Card Sorting Test (WCST). To assess the incidental recognition memory for item (object) and context (location of the object), participants of each group were assigned to 1 of 2 encoding conditions: (a) an incidental associative instruction to bind the object to its location or (b) a nonassociative, nonspecific instruction. Results. PD patients showed performance comparable to the control group`s on the vocabulary subtest and WCST. In contrast to controls, PD patients were unable to take advantage of the associative encoding instruction, which also had a deleterious effect on item recognition. Conclusion. This sample of participants with PD showed diminished item and context recognition memory and an impaired ability to use incidental memory encoding strategy, suggesting a compromised cognitive reserve. The fact that these alterations occurred in early stages of PD, and prior to more general cognitive alterations such as executive dysfunction, should be considered in the management of patients by using specific cognitive rehabilitation interventions.

Neuropsychological Outcome of Ventral Capsular/Ventral Striatal Gamma Capsulotomy for Refractory Obsessive-Compulsive Disorder: A Pilot Study

Five refractory obsessive-compulsive patients were assessed using a neuropsychological battery after a modified gamma knife capsulotomy. The surgical technique was not associated with profound cognitive deficits. The authors found improvements in attention, vocabulary, learning, abstract reasoning, and memory. (The journal of Neuropsychiatry and Clinical Neurosciences 2009; 21:393-397)

Neuropsychological Profile of Brazilian Older Adults with Heterogeneous Educational Backgrounds

Education significantly impacts cognitive performance of older adults even in the absence of dementia. Some cognitive tests seem less vulnerable to the influence of education and thus may be more suitable for cognitive assessment of older adults with heterogeneous backgrounds. The objective of this study was to investigate which tests in a cognitive battery were less influenced by educational levels in a sample of cognitively unimpaired older Brazilians. In addition, we evaluated the impact of very high educational levels on cognitive performance. The cognitive battery consisted of the Mini Mental State Examination (MMSE), Cambridge Cognitive Test (CAMCOG), Clock Drawing Test, Short Cognitive Performance Test (SKT), Rivermead Behavioural Memory Test (RBMT), Fuld Object Memory Evaluation (FOME), Verbal Fluency Test (VF) fruit category, Trail Making Test A and B, WAIS-R Vocabulary, and Block Design. Education did not exert a significant influence on the RBMT, FOME, and VF (p < .05). Subjects with very high educational levels had similar performance on the latter tests when compared with those with intermediate and low levels of education. In conclusion, the RBMT, FOME, and VF fruit category seem to be appropriate tools for the assessment of cognitive function in elderly Brazilians with varying degrees of educational attainment.

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.

A randomized double-blind placebo-controlled trial to increase feasibility of dobutamine stress echocardiography in patients with hypertension

Objective: To increase dobutamine stress echocardiography feasibility in patients with uncontrolled hypertension, we studied 729 consecutive patients referred for ischemia assessment. Methods: Patients with blood pressure ( BP) levels above 160/ 110 mm Hg were randomized to sublingual placebo or captopril ( 25 mg), and dobutamine stress echocardiography undertaken if BP decreased below 160/ 110 mm Hg after 15 minutes. Results: Of 149 patients ( 20%) with high BP levels, 104 ( 63 +/- 11 years, 51 male) were randomized. Baseline BP levels were similar for captopril ( 178 +/- 15/ 103 +/- 15 mm Hg) and placebo ( 181 +/- 17/ 103 +/- 15 mm Hg) groups. After intervention, 15 patients from captopril and 17 from placebo group had decreased BP ( 11% and 12% for systolic and 13% and 13% for diastolic BP, respectively). Five patients from placebo group ( P =.007) had to prematurely terminate the test because of hypertension ( BP > 220/ 120 mm Hg). Feasibility was similar for captopril and placebo groups ( 35% vs 25%, respectively, P = not significant). Conclusion: Although both captopril and placebo are effective in increasing dobutamine stress echocardiography feasibility in patients with uncontrolled BP, test interruption because of hypertension is less likely to occur after captopril administration.

CCR2 receptor is essential to activate microbicidal mechanisms to control Toxoplasma gondii infection in the central nervous system

Chemokines comprise a structurally related family of cytokines that regulate leukocyte trafficking. Because infection with Toxoplasma gondii can induce an important inflammatory reaction that, if left uncontrolled, can lead to death, we investigated the role of the chemokine receptor CCR2 in T gondii infection. We orally infected CCR2(-/-) mice with five ME-49 T gondii cysts and monitored morbidity, survival, and immune response thereafter. The CCR2(-/-) mice displayed higher susceptibility to infection as all mice died on day 28 after infection. Despite similar Th1 responses, a more evident anti-inflammatory response was induced in the peripheral organs of CCR2(-/-) mice compared with wild-type C57BL/6 mice. Additionally, CCR2-/- mice presented greater parasitism and a milder inflammatory reaction in their peripheral organs with lesser CD4(+) and MAC-1(+) and greater CD8(+) cell migration. The parasite load decreased in these organs in CCR2(-/-) mice but remained uncontrolled in the central nervous system. Additionally, we observed down-regulated inducible nitric oxide synthase expression in peripheral organs from CCR2(-/-) mice that was associated with a small nitric oxide production by spleen macrophages. In conclusion, in the absence of CCR2, another mechanism is activated to control tissue parasitism in peripheral organs. Nevertheless, CCR2 is essential for the activation of microbicidal mediators that control T gondii replication in the central nervous system.

Sudden unexpected death in an adolescent with epilepsy: All roads lead to the heart?

The incidence of sudden unexpected death in epilepsy (SUDEP) has been estimated from 0.5-1.4/1,000 person-years in people with treated epilepsy, and 9/1,000 person-years in candidates for epilepsy surgery. Potential risk factors for SUDEP include: age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure type and winter temperatures. The arrythmogenic side-effect of antiepileptic drugs and seizures may increase the risk of SUDEP. In this report, we describe a patient with prolonged post-ictal tachycardia in EEG video recordings with a typical case of SUDEP: a 16-year-old boy with medically intractable complex partial seizures. Magnetic resonance imaging revealed left mesial temporal sclerosis. During non-invasive video-EEG monitoring, the patient presented a post-ictal heart rate increased for five hours. Two months after video-EEG, he died from SUDEP during a tonic-clonic secondary generalized seizure. The possibility of cardiac involvement in the pathogenesis of SUDEP has been suggested by many studies. Evaluation of this patient with EEG-video monitoring, including measurement of heart rate, contributed to an identification of ictal tachycardia that may have played a role in the SUDEP. Premature mortality seems to be increased in patients with epilepsy, and cardiac abnormalities may be a possible cause of SUDEP. (Cardiol J 2011; 18, 2: 194-196)

Modulation of mucosal immunity in a murine model of food-induced intestinal inflammation

Background Hypersensitivity or uncontrolled responses against dietary antigens can lead to inflammatory disorders like food allergy and current models reflect a variety of causes but do not reveal the detailed modulation of gut immunity in response to food antigens after breakdown in mucosal tolerance. Objective To develop and characterize a murine model for food-induced intestinal inflammation and to demonstrate the modulation of gut immune response by dietary allergenic antigens. Methods C57BL/6 mice were sensitized with peanut proteins, challenged with peanut seeds and their sera and gut segments were collected for subsequent analyses. Results Sensitization and challenged with peanut seeds led to alterations in gut architecture with inflammatory response characterized by oedema in lamina propria and cell infiltrate composed mainly by eosinophils, mast cells, phagocytes, natural killer and plasma cells, together with low percentage of gamma delta(+) and CD4(+)CD25(+)Foxp3(+) cells in Peyer`s patches. These animals also presented high levels of specific IgE and IgG1 in sera and modulation of mucosal immunity was mediated by increased expression of GATA-3, IL-4, IL-13 and TNF-alpha in contrast to low IFN-gamma in the gut. Conclusion A murine model for food-induced intestinal inflammation was characterized in which modulation of gut immunity occurs by peanut antigens in consequence of T-helper type 2 (Th2) allergic response and failure of regulatory mechanisms necessary for mucosa homeostasis, resembling food allergy. This work shed some light on the understanding of the pathogenesis of gastrointestinal disorders and intolerance in the gut and supports the development of therapies for food-related enteropathies like food allergy, focusing on gut-specific immune response.

Increased cell proliferation in experimentally induced endometriosis in rabbits

Objective: To characterize the pattern of cell proliferation and apoptosis of eutopic and ectopic endometrium in rabbits after endometrium implantation for the experimental induction of endometriosis. Design: Animal experimental study. Setting: Sector of experimental surgery. Animal(s): Twenty-female New Zealand rabbits. Intervention(s): All animals underwent laparotomy for endometriosis induction by resection of one uterine horn, isolation of the endometrium, and fixation of tissue segment to the pelvic peritoneum. Two groups of 10 animals were sacrificed 4 and 8 weeks after endometriosis induction. The lesion was excised together with the opposite uterine horn for endometrial gland and stroma determination. Main Outcome Measure(s): Cell proliferation and apoptosis were determined in the eutopic and ectopic endometrium, and the cell proliferation index (CPI) and apoptotic index (AI) were calculated as the number of labeled cells per 1,000 cells. The tissue homeostasis index was the CPI/AI ratio. Glands and stroma were analyzed separately. Result(s): The CPI for ectopic tissue was increased compared with eutopic tissue, but there was no difference in the ectopic lesions between 4 and 8 weeks of induction. Considering only the AI, eutopic and ectopic endometrium did not differ after 4 weeks, but differed significantly in glandular tissue after 8 weeks. The tissue homeostasis index revealed cell proliferation in these tissues, with a CPI/AI more than 1. Conclusion(s): Ectopic lesions seem to have a higher CPI than eutopic endometrium, with uncontrolled tissue growth occurring in induced endometriotic lesions. (Fertil Steril (R) 2010;93:1637-42. (C)2010 by American Society for Reproductive Medicine.)

Glaucoma and Keratoprosthesis Surgery Role of Adjunctive Cyclophotocoagulation

Purpose: To evaluate the efficacy and safety of diode laser transscleral cyclophotocoagulation (DLTSC) to control intraocular pressure (IOP) in keratoprosthesis patients with uncontrolled glaucoma. Patients and Methods: Between 1993 and 2007, 18 eyes of 18 patients underwent DLTSC, either before (n = 3), during (n = I), or after (n = 14) keratoprosthesis surgery. Keratoprosthesis type 1 was used in 72%. All but one of these patients received an Ahmed Glaucoma Valve, either with or after the keratoprosthesis placement. Best-corrected visual acuity, IOP (assessed by digital palpation), number of medications, and complications were recorded preoperatively, at day 7, at 1, 3, and 6 months then every 6 months postoperatively. Results: Mean follow-tip was 26.6 +/- 19.6 months (mean +/- SD) and mean age was 50.1 +/- 15.6 years. Glaucoma was identified in 1 I eyes before keratoprosthesis surgery and in 7 eyes after. Mean postoperative IOP was significantly reduced at 6, 12, 24, 36, and 48 months after DLTSC. DLTSC was repeated in 6 eyes. At final visit, mean best-corrected visual acuity was not decreased and there were no statistically significant differences in the number of glaucoma medications. Two patients had complications after DLTSC: a conjunctival dehiscence and a fungal endophthalmitis. Conclusions: DLTSC has beneficial long-term effects in the control of IOP and can be considered in the management of keratoprosthesis patients with refractory glaucoma.

Proteomic analysis of low- to high-grade astrocytomas reveals an alteration of the expression level of raf kinase inhibitor protein and nucleophosmin

Proteomic approaches have been useful for the identification of aberrantly expressed proteins in complex diseases such as cancer. These proteins are not only potential disease biomarkers, but also targets for therapy. The aim of this study was to identify differentially expressed proteins in diffuse astrocytoma grade II, anaplastic astrocytoma grade III and glioblastoma multiforme grade IV in human tumor samples and in non-neoplastic brain tissue as control using 2-DE and MS. Tumor and control brain tissue dissection was guided by histological hematoxylin/eosin tissue sections to provide more than 90% of tumor cells and astrocytes. Six proteins were detected as up-regulated in higher grade astrocytomas and the most important finding was nucleophosmin (NPM) (p < 0.05), whereas four proteins were down-regulated, among them raf kinase inhibitor protein (RKIP) (p < 0.05). We report here for the first time the alteration of NPM and RKIP expression in brain cancer. Our focus on these proteins was due to the fact that they are involved in the PI3K/AKT/mTOR and RAS/RAF/MAPK pathways, known for their contribution to the development and progression of gliomas. The proteomic data for NPM and RKIP were confirmed by Western blot, quantitative real-time PCR and immunohistochemistry. Due to the participation of NPM and RKIP in uncontrolled proliferation and evasion of apoptosis, these proteins are likely targets for drug development.

The involvement of CD4(+)CD25(+) T cells in the acute phase of Trypanosoma cruzi infection

The infection with Trypanosoma cruzi leads to a vigorous and apparently uncontrolled inflammatory response in the heart. Although the parasites trigger specific immune response, the infection is not completely cleared out, a phenomenon that in other parasitic infections has been attributed to CD4(+)CD25(+) T cells (Tregs). Then, we examined the role of natural Tregs and its signaling through CD25 and GITR in the resistance against infection with T. cruzi. Mice were treated with mAb against CD25 and GITR and the parasitemia, mortality and heart pathology analyzed. First, we demonstrated that CD4(+)CD25(+)GITR(+)Foxp3(+) T cells migrate to the heart of infected mice. The treatment with anti-CD25 or anti-GITR resulted in increased mortality of these infected animals. Moreover, the treatment with anti-GITR enhanced the myocarditis, with increased migration of CD4(+), CD8(+), and CCR5(+) leukocytes, TNF-alpha production, and tissue parasitism, although it did not change the systemic nitric oxide synthesis. These data showed a limited role for CD25 signaling in controlling the inflammatory response during this protozoan infection. Also, the data suggested that signaling through GITR is determinant to control of the heart inflammation, parasite replication, and host resistance against the infection. (C) 2008 Elsevier Masson SAS. All rights reserved.

Could sudden death syndrome (SDS) in chickens (Gallus gallus) be a valid animal model for sudden unexpected death in epilepsy (SUDEP)?

Epilepsy is the most common serious neurological disorder and approximately 1% of the population worldwide has epilepsy. Moreover, sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning fisk factors for SUDEP is conflicting, but potential risk factors include: young age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure frequency, AED number and winter temperatures. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. Similarly, sudden death syndrome (SDS) is a disease characterized by an acute death of well-nourished and seeming healthy Gallus gallus after abrupt and brief flapping of their wings and incidence of SDS these animals has recently increased worldwide. Moreover, the exactly cause of SDS in Gallus gallus is unknown, but is very probable that cardiac abnormalities play a potential role. Due the similarities between SUDEP and SDS and as Gallus gallus behavioral manifestation during SDS phenomenon is close of a tonic-clonic seizure, in this paper we suggest that epilepsy could be a new possible causal factor for SDS. (C) 2009 Elsevier Ltd. All rights reserved.