Utility of Ictal Single Photon Emission Computed Tomography in Mesial Temporal Lobe Epilepsy With Hippocampal Atrophy: A Randomized Trial

BACKGROUND: The development of newer diagnostic technologies has reduced the need for invasive electroencephalographic (EEG) studies in identifying the epileptogenic zone, especially in adult patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS). OBJECTIVE: To evaluate ictal single photon emission computed tomography (SPECT) in the evaluation and treatment of patients with MTLE-HS. METHODS: MTLE patients were randomly assigned to those with (SPECT, n = 124) and without ictal SPECT (non-SPECT, n = 116) in an intent-to-treat protocol. Primary end points were the proportion of patients with invasive EEG studies, and those offered surgery. Secondary end points were the length of hospital stay and the proportion of patients with secondarily generalized seizures (SGS) during video-EEG, postsurgical seizure outcome, and hospital cost. RESULTS: The proportion of patients offered surgery was similar in the SPECT (85%) and non-SPECT groups (81%), as well as the proportion that had invasive EEG studies (27% vs 23%). The mean duration of hospital stay was 1 day longer for the SPECT group (P < 0.001). SGS occurred in 51% of the SPECT and 26% of the non-SPECT group (P < 0.001). The cost of the presurgical evaluation was 35% higher for the SPECT compared with the non-SPECT group (P < 0.001). The proportion of patients seizure-free after surgery was similar in the SPECT (59%) compared with non-SPECT group (54%). CONCLUSION: Ictal-SPECT did not add localizing value beyond what was provided by EEG-video telemetry and structural MRI that altered the surgical decision and outcome for MTLE-HS patients. Ictal-SPECT increased hospital stay was associated with increased costs and a higher chance of SGS during video-EEG monitoring. These findings support the notion that a protocol including ictal SPECT is equivalent to one without SPECT in the presurgical evaluation of adult patients with MTLE-HS.

Effects of hyperbaric oxygen treatment on auditory hair cells after acute noise damage

Acute acoustic trauma (AAT) is a sudden sensorineural hearing loss caused by exposure of the hearing organ to acoustic overstimulation, typically an intense sound impulse, hyperbaric oxygen therapy (HOT), which favors repair of the microcirculation, can be potentially used to treat it. Hence, this study aimed to assess the effects of HOT on guinea pigs exposed to acoustic trauma. Fifteen guinea pigs were exposed to noise in the 4-kHz range with intensity of 110 dB sound level pressure for 72 h. They were assessed by brainstem auditory evoked potential (BAEP) and by distortion product otoacoustic emission (DPOAE) before and after exposure and after HOT at 2.0 absolute atmospheres for 1 h. The cochleae were then analyzed using scanning electron microscopy (SEM). There was a statistically significant difference in the signal-to-noise ratio of the DPOAE amplitudes for the 1- to 4-kHz frequencies and the SEM findings revealed damaged outer hair cells (OHC) after exposure to noise, with recovery after HOT (p = 0.0159), which did not occur on thresholds and amplitudes to BAEP (p = 0.1593). The electrophysiological BAEP data did not demonstrate effectiveness of HOT against AAT damage. However, there was improvement of the anatomical pattern of damage detected by SEM, with a significant reduction of the number of injured cochlear OHC and their functionality detected by DPOAE.

Multiple cranial burr holes as an alternative treatment for total scalp avulsion

Total scalp avulsion is a devastating injury in clinical practice. It often occurs in female adults, being rare in children. The standard treatment for scalp avulsion is microsurgical replantation, when feasible. Coverage becomes a major problem when replantation fails or is contraindicated, resulting in significant morbidity and requiring multiple procedures. In this article, in addition to reviewing the literature, we report a historical method for obtaining skin coverage after failure of replantation. The authors report a case of a 10-year-old girl who had her scalp totally avulsed by an agricultural machine, including her right auricle. Microsurgery scalp replantation was attempted immediately after fluid resuscitation. The surgery failed probably due to the long time interval between trauma and surgery, which resulted in total ischemic time of 11 h and consequently made vascular microanastomosis impracticable. Multiple trephination of the calvarium was performed in order to expose the diploe. After 4 weeks, granulation tissue from the holes began to cover the defect, allowing the formation of a vascular bed suitable for skin grafting. Total scalp avulsion in children is seldom reported in the literature. Therefore, its management is both difficult and challenging. The exposure of the diploe with multiple burr holes is a safe and effective method for treating this injury. It may be considered, along with skin grafting, a good therapeutic alternative to be used when microsurgical replantation fails or is not feasible.

Why Not to Use Kidney Grafts From Elderly Donors

Background. Kidney transplantation is widely recognized as the best treatment in patients who require renal replacement therapy. Although considered a clinical and surgical triumph, it is also a source of frustration because of lack of donor organs and the growth of waiting lists. Strategies need to be developed to increase the supply of organs. One measure is use of expanded criteria for donation. Objective. To evaluate the effect of donor age on cadaver graft survival. Materials and Methods. We reviewed the medical records for 454 patients who underwent kidney transplantation with cadaver donors from April 1987 to December 2003. Results. Donor age had a significant effect on kidney transplant survival. Survival of grafts from donors aged 16 to 40 years (mean, 143.30 months) was significantly greater compared with that of grafts from donors older than 40 years (66.46 months) (P = .005). The HLA matching and cold ischemia time did not significantly affect transplant survival (P = .98 and P = .16, respectively). Conclusions. Kidneys from cadaver donors older than 40 years significantly compromised graft survival, generating a negative effect via early return of recipients to waiting lists and increasing the rate of repeat transplantation, risk of death, and unnecessary costs.

Ethical issues in neuroscience research on substance dependence treatment and prevention

Previous chapters have presented the latest findings in neuroscience research, and have pointed to potential treatment and prevention strategies. However, there are many ethical implications of the research itself, as well as the treatment and prevention strategies, that must be considered. The rapid pace of change in the field of neuroscience brings with it a host of new ethical issues, which need to be addressed. This chapter considers the important ethical and human rights issues that are raised by neuroscience research on psychoactive substance dependence.

Concurrent chemoradiotherapy with weekly paclitaxel in malignant cerebral glioma treatment

Background: Anaplastic astrocytomas (AA) and glioblastomas (GB) are the most common malignant gliomas, and despite newly developed drugs and combined treatments, they still have an adverse prognosis. Paclitaxel is a cytotoxic agent with radiosensitizing properties and exerts objective growth inhibition in glioma tumor cells. Patients and Methods: From 1998 to 2002, 61 microneuro-surgically treated patients were randomized to group I (18 GB, 14 AA) which received radiotherapy and weekly paclitaxel at dose of 100 mg/m(2), and group II (21 GB, 8 AA) which received only radiotherapy as a complementary treatment. Results: Median overall survival was 27.96 months in group I and 23.06 months in group II with no statistical difference. The 12-month survival was 81% in group I and 76% in group II. Kaplan-Meier curves of both groups did not demonstrate any difference. Analysis of each histological subgroup (AA or GB) also showed no statistical difference in the survival curves. All 427 cycles were well tolerated with no treatment-associated deaths. Conclusions: Chemoradiotherapy with weekly paclitaxel is safe and tolerable although there was no increase in the overall survival and 12-month survival of malignant glioma patients. Further investigations modulating the paclitaxel entrance and delivery into the brain should be encouraged.

Single-Step EUS-Guided Endoscopic Treatment for Sterile Pancreatic Collections: A Single-Center Experience

Background and Aims: Endoscopic ultrasound (EUS) is useful for the treatment of sterile pancreatic fluid collections (PFC), either by means of transmural drainage or by complete aspiration. The aim of this study was to evaluate the efficacy and safety of single-step EUS-guided endoscopic approaches for treatment of sterile PFC. Patients and Methods: During a 3-year period, 77 consecutive patients with symptomatic, persistent sterile PFC were evaluated and treated with the linear EUS. We excluded patients with grossly purulent collections, chronic pseudocyst and those whose cytology diagnostic was neoplastic cyst of pancreas. 44 patients received a single 10-Fr plastic straight stent under EUS or fluoroscopic control (group I) and 33 of these underwent a single-step complete aspiration with a 19-gauge needle (group II). Results: The mean size of the sterile PFC was 48 mm in group I and 28 mm in group II (p < 0.001). Overall, endoscopic treatment was successful in 70 (90.9%) patients. The mean volume aspirated was 25 (18-65) ml. The total number of procedures was 50 in group I and 41 punctures in group II. After a mean follow-up of 64 +/- 15.6 weeks there were 6 complications 13.6%): 2 recurrences (referred to surgery), 2 developing abscesses (submitted a new EUS-guided endoscopic drainage with success), 1 perforation that died (2.2%), and 1 case of bleeding (sent to surgery) in group I. In group II there were only 6 (18.1%) recurrences (submitted a new EUS-guided aspiration). None of the patients undergoing single-step aspiration developed infections, perforation or hemorrhage. Conclusion: The recurrence of pancreatic pseudocysts after endoscopic treatment was similar, either by means of plastic stents or by complete single-step aspiration. Copyright (C) 2009 S. Karger AG, Basel

Stable and high-level production of recombinant Factor IX in human hepatic cell line

Hemophilia B is a genetic disease of the coagulation system that affects one in 30,000 males worldwide. Recombinant human Factor IX (rhFIX) has been used for hemophilia B treatment, but the amount of active protein generated by these systems is inefficient, resulting in a high-cost production of rhFIX. In this study, we developed an alternative for rhFIX production. We used a retrovirus system to obtain two recombinant cell lines. We first tested rhFIX production in the human embryonic kidney 293 cells (293). Next, we tested a hepatic cell line (HepG2) because FIX is primarily expressed in the liver. Our results reveal that intracellular rhFIX expression was more efficient in HepG2/rhFIX (46%) than in 293/rhFIX (21%). The activated partial thromboplastin time test showed that HepG2/rhFIX expressed biologically active rhFIX 1.5 times higher than 293/rhFIX (P = 0.016). Recovery of rhFIX from the HepG2 by reversed-phase chromatography was straightforward. We found that rhFIX has a pharmacokinetic profile similar to that of FIX purified from human plasma when tested in hemophilic B model. HepG2/rhFIX cell line produced the highest levels of rhFIX, representing an efficient in vitro expression system. This work opens up the possibility of significantly reducing the costs of rhFIX production, with implications for expanding hemophilia B treatment in developing countries.

Differential gene expression of peripheral blood mononuclear cells from rheumatoid arthritis patients may discriminate immunogenetic, pathogenic and treatment features

This study aimed to evaluate the association between the differential gene expression profiling of peripheral blood mononuclear cells of rheumatoid arthritis patients with their immunogenetic (human leucocyte antigen shared-epitope, HLA-SE), autoimmune response [anti-cyclic citrullinated peptide (CCP) antibodies], disease activity score (DAS-28) and treatment (disease-modifying antirheumatic drugs and tumour necrosis factor blocker) features. Total RNA samples were copied into Cy3-labelled complementary DNA probes, hybridized onto a glass slide microarray containing 4500 human IMAGE complementary DNA target sequences. The Cy3-monocolour microarray images from patients were quantified and normalized. Analysis of the data using the significance analysis of microarrays algorithm together with a Venn diagram allowed the identification of shared and of exclusively modulated genes, according to patient features. Thirteen genes were exclusively associated with the presence of HLA-SE alleles, whose major biological function was related to signal transduction, phosphorylation and apoptosis. Ninety-one genes were associated with disease activity, being involved in signal transduction, apoptosis, response to stress and DNA damage. One hundred and one genes were associated with the presence of anti-CCP antibodies, being involved in signal transduction, cell proliferation and apoptosis. Twenty-eight genes were associated with tumour necrosis factor blocker treatment, being involved in intracellular signalling cascade, phosphorylation and protein transport. Some of these genes had been previously associated with rheumatoid arthritis pathogenesis, whereas others were unveiled for future research.

Immunohistochemical Expression of HLA-DR in the Conjunctiva of Patients Under Topical Prostaglandin Analogs Treatment

Purpose: Subclinical inflammation may be observed in patients, using topical antiglaucomatous drugs. The objective,e of this study was to investigate inflammation in conjunctiva of glaucoma patients using prostaglandin analogs, by the detection of a immunogenetic marker (HLA-DR) and compare the effect of 3 different drugs: latanoprost, bimatoprost, and travoprost in the induction of this inflammation. Subjects and Methods: Thirty-three patients with primary open-angle glaucoma were evaluated without and with prostaglandin analogs topical therapy. Imprints of conjunctival cells were obtained, fixed on glass slides. and Prepared for immunohistochemical analysis. Results: Before the use of prostaglandin analogs, 4 of the 33 patients evaluated presented expression (of HLA-DR in the conjunctiva (mild). After 1 month oil prostaglandin analog treatment, all but 1 patient presented HLA-DR staining. HLA-DR expression of these 32 patients was scored as mild (19 patients), medium (11 patients), or intense (2 patients). The differences were statistically significant both when the presence and the increased expression of HLA-DR were considered (P<0.001). When the 3 different groups were analyzed (latanoprost, bimatoprost, and travoprost) no statistically significant difference was round (P 0.27). Conclusions: The use of prostaglandin analogs eye drops provokes, a reaction, observed by HLA-DR subclinical inflammatory expression, even after a short period of treatment, independently of the class of the prostaglandin analogs used.

Consequences of lifetime isolated growth hormone (GH) deficiency and effects of short-term GH treatment on bone in adults with a mutation in the GHRH-receptor gene

Growth hormone (GH) influences bone mass maintenance. However, the consequences of lifetime isolated GH deficiency (IGHD) on bone are not well established. We assessed the bone status and the effect of 6 months of GH replacement in GH-naive adults with IGHD due to a homozygous mutation of the GH-releasing hormone (GHRH)-receptor gene (GHRHR). We studied 20 individuals (10 men) with IGHD at baseline, after 6 months of depot GH treatment, and 6 and 12 months after discontinuation of GH. Quantitative ultrasound (QUS) of the heel was performed and serum osteocalcin (OC) and C-terminal cross-linking telopeptide of type I collagen (ICTP) were measured. QUS was also performed at baseline and 12 months later in a group of 20 normal control individuals (CO), who did not receive GH treatment. At baseline, the IGHD group had a lower T-score on QUS than CO (-1.15 +/- 0.9 vs. -0.07 +/- 0.9, P < 0.001). GH treatment improved this parameter, with improvement persisting for 12 months post-treatment (T-score for IGHD = -0.59 +/- 0.9, P < 0.05). GH also caused an increase in serum OC (baseline vs. pGH, P < 0.001) and ICTP (baseline vs. pGH, P < 0.01). The increase in OC was more marked during treatment and its reduction was slower after GH discontinuation than in ICTP. These data suggest that lifetime severe IGHD is associated with significant reduction in QUS parameters, which are partially reversed by short-term depot GH treatment. The treatment induces a biochemical pattern of bone anabolism that persists for at least 6 months after treatment discontinuation.

Inflammatory and functional effects of increasing asthma treatment with formoterol or double dose budesonide

Adding a long-acting beta(2)-agonist to inhaled corticosteroids (ICS) for asthma treatment is better than increasing ICS dose in improving clinical status, although there is no consensus about the impact of this regimen on inflammation. In this double-blind, randomized, parallel group study, asthmatics with moderate to severe disease used budesonide (400 mcg/day) for 5 weeks (run-in period); then they were randomized to use budesonide (800 mcg/day - BUD group) or budesonide plus formoterol (400 mcg and 24 mcg/day, respectively - FORMO group) for 9 weeks (treatment period). Home PEF measurements, symptom daily reporting, spirometry, sputum induction (for differential cell counts and sputum cell cultures), and hypertonic saline bronchial challenge test were performed before and after treatments. TNF-alpha, IL-4 and eotaxin-2 levels in the sputum and cell culture supernatants were determined. Morning and night PEF values increased in the FORMO group during the treatment period (p < 0.01), from 435 +/- 162 to 489 +/- 169 and 428 +/- 160 to 496 +/- 173 L/min, respectively. The rate of exacerbations in the FORMO group was lower than in the BUD group (p < 0.05). Neutrophil counts in sputum increased in both groups (p < 0.05) and leukocyte viability after 48 h-culture increased in the FORMO group (p < 0.05). No other parameter changed significantly in either group. This study showed that adding formoterol to budesonide improved home PEF and provided protection from exacerbations, although increase of leukocyte viability in cell culture may be a matter of concern and needs further investigation. (C) 2008 Elsevier Ltd. All rights reserved.