The Consequences Of Refractory Epilepsy And Its Treatment.

Seizures in some 30% to 40% of patients with epilepsy fail to respond to antiepileptic drugs or other treatments. While much has been made of the risks of new drug therapies, not enough attention has been given to the risks of uncontrolled and progressive epilepsy. This critical review summarizes known risks associated with refractory epilepsy, provides practical clinical recommendations, and indicates areas for future research. Eight international epilepsy experts from Europe, the United States, and South America met on May 4, 2013, to present, review, and discuss relevant concepts, data, and literature on the consequences of refractory epilepsy. While patients with refractory epilepsy represent the minority of the population with epilepsy, they require the overwhelming majority of time, effort, and focus from treating physicians. They also represent the greatest economic and psychosocial burdens. Diagnostic procedures and medical/surgical treatments are not without risks. Overlooked, however, is that these risks are usually smaller than the risks of long-term, uncontrolled seizures. Refractory epilepsy may be progressive, carrying risks of structural damage to the brain and nervous system, comorbidities (osteoporosis, fractures), and increased mortality (from suicide, accidents, sudden unexpected death in epilepsy, pneumonia, vascular disease), as well as psychological (depression, anxiety), educational, social (stigma, driving), and vocational consequences. Adding to this burden is neuropsychiatric impairment caused by underlying epileptogenic processes (essential comorbidities), which appears to be independent of the effects of ongoing seizures themselves. Tolerating persistent seizures or chronic medicinal adverse effects has risks and consequences that often outweigh risks of seemingly more aggressive treatments. Future research should focus not only on controlling seizures but also on preventing these consequences.

Influence Of Gastric Emptying On The Control Of Postprandial Glycemia: Physiology And Therapeutic Implications.

The maintenance of glucose homeostasis is complex and involves, besides the secretion and action of insulin and glucagon, a hormonal and neural mechanism, regulating the rate of gastric emptying. This mechanism depends on extrinsic and intrinsic factors. Glucagon-like peptide-1 secretion regulates the speed of gastric emptying, contributing to the control of postprandial glycemia. The pharmacodynamic characteristics of various agents of this class can explain the effects more relevant in fasting or postprandial glucose, and can thus guide the individualized treatment, according to the clinical and pathophysiological features of each patient.

A Microleakage Study Of Gutta-percha/ah Plus And Resilon/real Self-etch Systems After Different Irrigation Protocols.

The development and maintenance of the sealing of the root canal system is the key to the success of root canal treatment. The resin-based adhesive material has the potential to reduce the microleakage of the root canal because of its adhesive properties and penetration into dentinal walls. Moreover, the irrigation protocols may have an influence on the adhesiveness of resin-based sealers to root dentin. The objective of the present study was to evaluate the effect of different irrigant protocols on coronal bacterial microleakage of gutta-percha/AH Plus and Resilon/Real Seal Self-etch systems. One hundred ninety pre-molars were used. The teeth were divided into 18 experimental groups according to the irrigation protocols and filling materials used. The protocols used were: distilled water; sodium hypochlorite (NaOCl)+eDTA; NaOCl+H3PO4; NaOCl+eDTA+chlorhexidine (CHX); NaOCl+H3PO4+CHX; CHX+eDTA; CHX+ H3PO4; CHX+eDTA+CHX and CHX+H3PO4+CHX. Gutta-percha/AH Plus or Resilon/Real Seal Se were used as root-filling materials. The coronal microleakage was evaluated for 90 days against Enterococcus faecalis. Data were statistically analyzed using Kaplan-Meier survival test, Kruskal-Wallis and Mann-Whitney tests. No significant difference was verified in the groups using chlorhexidine or sodium hypochlorite during the chemo-mechanical preparation followed by eDTA or phosphoric acid for smear layer removal. The same results were found for filling materials. However, the statistical analyses revealed that a final flush with 2% chlorhexidine reduced significantly the coronal microleakage. A final flush with 2% chlorhexidine after smear layer removal reduces coronal microleakage of teeth filled with gutta-percha/AH Plus or Resilon/Real Seal SE.

Effects Of High Pressure Homogenization On The Activity, Stability, Kinetics And Three-dimensional Conformation Of A Glucose Oxidase Produced By Aspergillus Niger.

High pressure homogenization (HPH) is a non-thermal method, which has been employed to change the activity and stability of biotechnologically relevant enzymes. This work investigated how HPH affects the structural and functional characteristics of a glucose oxidase (GO) from Aspergillus niger. The enzyme was homogenized at 75 and 150 MPa and the effects were evaluated with respect to the enzyme activity, stability, kinetic parameters and molecular structure. The enzyme showed a pH-dependent response to the HPH treatment, with reduction or maintenance of activity at pH 4.5-6.0 and a remarkable activity increase (30-300%) at pH 6.5 in all tested temperatures (15, 50 and 75°C). The enzyme thermal tolerance was reduced due to HPH treatment and the storage for 24 h at high temperatures (50 and 75°C) also caused a reduction of activity. Interestingly, at lower temperatures (15°C) the activity levels were slightly higher than that observed for native enzyme or at least maintained. These effects of HPH treatment on function and stability of GO were further investigated by spectroscopic methods. Both fluorescence and circular dichroism revealed conformational changes in the molecular structure of the enzyme that might be associated with the distinct functional and stability behavior of GO.

[adherence To Statin Treatment And Associated Factors In Female Users From The Unified Health System (sus)].

To identify the adherence rate of a statin treatment and possible related factors in female users from the Unified Health System. Seventy-one women were evaluated (64.2 ± 11.0 years) regarding the socio-economic level, comorbidities, current medications, level of physical activity, self-report of muscular pain, adherence to the medical prescription, body composition and biochemical profile. The data were analyzed as frequencies, Chi-Squared test, and Mann Whitney test (p<0.05). 15.5% of women did not adhere to the medical prescription for the statin treatment, whose had less comorbidities (p=0.01), consumed less quantities of medications (p=0.00), and tended to be younger (p=0.06). Those patients also presented higher values of lipid profile (CT: p=0.01; LDL-c: p=0.02). Musculoskeletal complains were not associated to the adherence rate to the medication. The associated factors to adherence of dyslipidemic women to statin medical prescription were age, quantity of comorbidities and quantity of current medication.

Familial Systemic Mastocytosis With Germline Kit K509i Mutation Is Sensitive To Treatment With Imatinib, Dasatinib And Pkc412.

Mastocytosis are myeloproliferative neoplasms commonly related to gain-of-function mutations involving the tyrosine kinase domain of KIT. We herein report a case of familial systemic mastocytosis with the rare KIT K509I germ line mutation affecting two family members: mother and daughter. In vitro treatment with imatinib, dasatinib and PKC412 reduced cell viability of primary mast cells harboring KIT K509I mutation. However, imatinib was more effective in inducing apoptosis of neoplastic mast cells. Both patients with familial systemic mastocytosis had remarkable hematological and skin improvement after three months of imatinib treatment, suggesting that it may be an effective front line therapy for patients harboring KIT K509I mutation.

Unfavorable Outcomes During Treatment Of Multiple Sclerosis With High Doses Of Vitamin D.

346

Reduced Plasma Angiotensin Ii Levels Are Reversed By Hydroxyurea Treatment In Mice With Sickle Cell Disease.

Sickle cell disease (SCD) pathogenesis leads to recurrent vaso-occlusive and hemolytic processes, causing numerous clinical complications including renal damage. As vasoconstrictive mechanisms may be enhanced in SCD, due to endothelial dysfunction and vasoactive protein production, we aimed to determine whether the expression of proteins of the renin-angiotensin system (RAS) may be altered in an animal model of SCD. Plasma angiotensin II (Ang II) was measured in C57BL/6 (WT) mice and mice with SCD by ELISA, while quantitative PCR was used to compare the expressions of the genes encoding the angiotensin-II-receptors 1 and 2 (AT1R and AT2R) and the angiotensin-converting enzymes (ACE1 and ACE2) in the kidneys, hearts, livers and brains of mice. The effects of hydroxyurea (HU; 50-75mg/kg/day, 4weeks) treatment on these parameters were also determined. Plasma Ang II was significantly diminished in SCD mice, compared with WT mice, in association with decreased AT1R and ACE1 expressions in SCD mice kidneys. Treatment of SCD mice with HU reduced leukocyte and platelet counts and increased plasma Ang II to levels similar to those of WT mice. HU also increased AT1R and ACE2 gene expression in the kidney and heart. Results indicate an imbalanced RAS in an SCD mouse model; HU therapy may be able to restore some RAS parameters in these mice. Further investigations regarding Ang II production and the RAS in human SCD may be warranted, as such changes may reflect or contribute to renal damage and alterations in blood pressure.

Direct Adhesive Pin-retained Restorations For Severely Worn Dentition Treatment: A 1.5-year Follow-up Report.

Excessive occlusal surface wear can result in occlusal disharmony, functional and esthetic impairment. As a therapeutic approach, conventional single crowns have been proposed, but this kind of treatment is complex, highly invasive and expensive. This case report describes the clinical outcomes of an alternative minimally invasive treatment based on direct adhesive-pin retained restorations. A 64-year-old woman with severely worn dentition, eating problems related to missing teeth and generalized tooth hypersensitivity was referred for treatment. Proper treatment planning based on the diagnostic wax-up simulation was used to guide the reconstruction of maxillary anterior teeth with direct composite resin over self-threading dentin pins. As the mandibular remaining teeth were extremely worn, a tooth-supported overdenture was installed. A stabilization splint was also used to protect the restorations. This treatment was a less expensive alternative to full-mouth rehabilitation with positive esthetic and functional outcomes after 1.5 years of follow-up.

Beliefs Related To Adherence To Oral Antidiabetic Treatment According To The Theory Of Planned Behavior.

to identify salient behavioral, normative, control and self-efficacy beliefs related to the behavior of adherence to oral antidiabetic agents, using the Theory of Planned Behavior. cross-sectional, exploratory study with 17 diabetic patients in chronic use of oral antidiabetic medication and in outpatient follow-up. Individual interviews were recorded, transcribed and content-analyzed using pre-established categories. behavioral beliefs concerning advantages and disadvantages of adhering to medication emerged, such as the possibility of avoiding complications from diabetes, preventing or delaying the use of insulin, and a perception of side effects. The children of patients and physicians are seen as important social references who influence medication adherence. The factors that facilitate adherence include access to free-of-cost medication and taking medications associated with temporal markers. On the other hand, a complex therapeutic regimen was considered a factor that hinders adherence. Understanding how to use medication and forgetfulness impact the perception of patients regarding their ability to adhere to oral antidiabetic agents. medication adherence is a complex behavior permeated by behavioral, normative, control and self-efficacy beliefs that should be taken into account when assessing determinants of behavior.

[larynx Cancer: Quality Of Life And Voice After Treatment].

Treatments for patients with laryngeal cancer often have an impact on physical, social, and psychological functions. To evaluate quality of life and voice in patients treated for advanced laryngeal cancer through surgery or exclusive chemoradiation. Retrospective cohort study with 30 patients free from disease: ten total laryngectomy patients without production of esophageal speech (ES); ten total laryngectomy patients with tracheoesophageal speech (TES), and ten with laryngeal speech. Quality of life was measured by SF-36, Voice-Related Quality of Life (V-RQOL), and Voice Handicap Index (VHI) protocols, applied on the same day. The SF-36 showed that patients who received exclusive chemoradiotherapy had better quality of life than the TES and ES groups. The V-RQOL showed that the voice-related quality of life was lower in the ES group. In the VHI, the ES group showed higher scores for overall, emotional, functional, and organic VHI. Quality of life and voice in patients treated with chemoradiotherapy was better than in patients treated surgically. The type of medical treatment used in patients with laryngeal cancer can bring changes in quality of life and voice.

Comparative Study Of Planned And Unplanned Excisions For The Treatment Of Soft Tissue Sarcoma Of The Extremities.

Unplanned excision of soft tissue sarcomas is common because benign soft tissue lesions are very frequent. This study evaluated the impact of unplanned resections on overall survival, local recurrence and distant metastasis in patients with soft tissue sarcomas of the extremities. In total, 52 patients who were diagnosed with soft tissue sarcomas between May 2001 and March 2011 were analyzed in a retrospective study. Of these patients, 29 (55.8%) had not undergone previous treatment and the remaining 23 (44.2%) patients had undergone prior resection of the tumor without oncological planning. All subsequent surgical procedures were performed at the same cancer referral center. The follow-up ranged from 6 to 122 months, with a mean of 39.89 months. Age, lesion size and depth, histological grade, surgical margins, overall survival, local and distant recurrence and adjuvant therapies were compared. Residual disease was observed in 91.3% of the re-resected specimens in the unplanned excision group, which exhibited greater numbers of superficial lesions, low histological grades and contaminated surgical margins compared with the re-resected specimens in the planned excision group. No differences were observed in local recurrence and 5-year overall survival between the groups, but distant metastases were significantly associated with planned excision after adjustment for the variables. There was no difference between patients undergoing unplanned excision and planned excision regarding local recurrence and overall survival. The planned excision group had a higher risk of distant metastasis, whereas there was a high rate of residual cancer in the unplanned excision group.

Long-term Spinal Ventral Root Reimplantation, But Not Bone Marrow Mononuclear Cell Treatment, Positively Influences Ultrastructural Synapse Recovery And Motor Axonal Regrowth.

We recently proposed a new surgical approach to treat ventral root avulsion, resulting in motoneuron protection. The present work combined such a surgical approach with bone marrow mononuclear cells (MC) therapy. Therefore, MC were added to the site of reimplantation. Female Lewis rats (seven weeks old) were subjected to unilateral ventral root avulsion (VRA) at L4, L5 and L6 levels and divided into the following groups (n = 5 for each group): Avulsion, sealant reimplanted roots and sealant reimplanted roots plus MC. After four weeks and 12 weeks post-surgery, the lumbar intumescences were processed by transmission electron microscopy, to analyze synaptic inputs to the repaired α motoneurons. Also, the ipsi and contralateral sciatic nerves were processed for axon counting and morphometry. The ultrastructural results indicated a significant preservation of inhibitory pre-synaptic boutons in the groups repaired with sealant alone and associated with MC therapy. Moreover, the average number of axons was higher in treated groups when compared to avulsion only. Complementary to the fiber counting, the morphometric analysis of axonal diameter and g ratio demonstrated that root reimplantation improved the motor component recovery. In conclusion, the data herein demonstrate that root reimplantation at the lesion site may be considered a therapeutic approach, following proximal lesions in the interface of central nervous system (CNS) and peripheral nervous system (PNS), and that MC therapy does not further improve the regenerative recovery, up to 12 weeks post lesion.

Impact Of Pregabalin Treatment On Synaptic Plasticity And Glial Reactivity During The Course Of Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease that affects young adults. It is characterized by generating a chronic demyelinating autoimmune inflammation in the central nervous system. An experimental model for studying MS is the experimental autoimmune encephalomyelitis (EAE), induced by immunization with antigenic proteins from myelin. The present study investigated the evolution of EAE in pregabalin treated animals up to the remission phase. The results demonstrated a delay in the onset of the disease with statistical differences at the 10th and the 16th day after immunization. Additionally, the walking track test (CatWalk) was used to evaluate different parameters related to motor function. Although no difference between groups was obtained for the foot print pressure, the regularity index was improved post treatment, indicating a better motor coordination. The immunohistochemical analysis of putative synapse preservation and glial reactivity revealed that pregabalin treatment improved the overall morphology of the spinal cord. A preservation of circuits was depicted and the glial reaction was downregulated during the course of the disease. qRT-PCR data did not show immunomodulatory effects of pregabalin, indicating that the positive effects were restricted to the CNS environment. Overall, the present data indicate that pregabalin is efficient for reducing the seriousness of EAE, delaying its course as well as reducing synaptic loss and astroglial reaction.

Diagnosis, Treatment, And Follow-up Of Medullary Thyroid Carcinoma: Recommendations By The Thyroid Department Of The Brazilian Society Of Endocrinology And Metabolism.

Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and represents 3-4% of the malignant neoplasms that affect this gland. Approximately 25% of these cases are hereditary due to activating mutations in the REarranged during Transfection (RET) proto-oncogene. The course of MTC is indolent, and survival rates depend on the tumor stage at diagnosis. The present article describes clinical evidence-based guidelines for the diagnosis, treatment, and follow-up of MTC. The aim of the consensus described herein, which was elaborated by Brazilian experts and sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism, was to discuss the diagnosis, treatment, and follow-up of individuals with MTC in accordance with the latest evidence reported in the literature. After clinical questions were elaborated, the available literature was initially surveyed for evidence in the MedLine-PubMed database, followed by the Embase and Scientific Electronic Library Online/Latin American and Caribbean Health Science Literature (SciELO/Lilacs) databases. The strength of evidence was assessed according to the Oxford classification of evidence levels, which is based on study design, and the best evidence available for each question was selected. Eleven questions corresponded to MTC diagnosis, 8 corresponded to its surgical treatment, and 13 corresponded to follow-up, for a total of 32 recommendations. The present article discusses the clinical and molecular diagnosis, initial surgical treatment, and postoperative management of MTC, as well as the therapeutic options for metastatic disease. MTC should be suspected in individuals who present with thyroid nodules and family histories of MTC, associations with pheochromocytoma and hyperparathyroidism, and/or typical phenotypic characteristics such as ganglioneuromatosis and Marfanoid habitus. Fine-needle nodule aspiration, serum calcitonin measurements, and anatomical-pathological examinations are useful for diagnostic confirmation. Surgery represents the only curative therapeutic strategy. The therapeutic options for metastatic disease remain limited and are restricted to disease control. Judicious postoperative assessments that focus on the identification of residual or recurrent disease are of paramount importance when defining the follow-up and later therapeutic management strategies.