Drug utilisation study in patients receiving antiepileptic drugs in Colombia.

INTRODUCTION: This study examines the indications according to which antiepileptic drugs are prescribed and used in a population of patients enrolled in the Colombian national health system (SGSSS). METHODS: Retrospective cross-sectional study. From the pool of individuals in 34 Colombian cities who used antiepileptic drugs between 18 July, 2013 and 31 August, 2014 during a period of no less than 12 months, we obtained a random sample stratified by city. Socio-demographic, pharmacological and comorbidity variables were analysed. Continuous and categorical variables were compared, and logistic regression models were used. RESULTS: Our patient total was 373 patients, with 197 women (52.1%) and a mean age of 41.9 ± 21.7 years; 65.4% of the patients were treated with monotherapy. The most frequently used drugs were valproic acid (53.1%) and carbamazepine (33.2%). Epilepsy was the most frequent indication (n=178; 47.7%); however, 52.3% of the patients were prescribed antiepileptics for different indications, especially neuropathic pain (26.8%), affective disorders (14.2%) and migraine prophylaxis (12.3%). A total of 81 patients with epilepsy (46.6%) displayed good seizure control while another 25 (14.4%) had drug-resistant epilepsy. In the multivariate analysis, medication adherence was associated with a lower risk of treatment failure in patients with epilepsy (OR: 0.27; 95%CI, 0.11-0.67). CONCLUSIONS: In Colombia, antiepileptic drugs are being used for indications other than those originally intended. Monotherapy is the most commonly used treatment approach, together with the use of classic antiepileptic drugs.

Green Tea Prevents NAFLD by Modulation of miR-34a and miR-194 Expression in a High-Fat Diet Mouse Model.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. It is currently the most common chronic liver disease with complex pathogenesis and challenging treatment. Here, we investigated the hepatoprotective role of green tea (GT) and determined the involvement of miRNAs and its mechanism of action. METHODS: Male C57Bl/6 mice were fed with a high-fat diet for 4 weeks. After this period, the animals received gavage with GT (500 mg/kg body weight) over 12 weeks (5 days/week). HepG2 cell lines were transfected with miR-34a or miR-194 mimetics and inhibitors to validate the in vivo results or were treated with TNF-α to evaluate miRNA regulation. RESULTS: GT supplementation protects against NAFLD development by altering lipid metabolism, increasing gene expression involved in triglycerides and fatty acid catabolism, and decreasing uptake and lipid accumulation. This phenotype was accompanied by miR-34a downregulation and an increase in their mRNA targets Sirt1, Pparα, and Insig2. GT upregulated hepatic miR-194 by inhibiting TNF-α action leading to a decrease in miR-194 target genes Hmgcs/Apoa5. CONCLUSION: Our study identified for the first time that the beneficial effects of GT in the liver can be due to the modulation of miRNAs, opening new perspectives for the treatment of NAFLD focusing on epigenetic regulation of miR-34a and miR-194 as green tea targets.

[Patterns of antidemential drug use in a group of patients from Colombia]. / Patrones de uso de farmacos antidemencia en un grupo de pacientes de Colombia.

INTRODUCTION: The benefits of pharmacological therapy with anti-dementia drugs are not yet fully demonstrated and there is even a lack of publications describing their use profile. The present work sought to determine the prescription patterns of anti-dementia drugs in a Colombian population. PATIENTS AND METHODS: Descriptive cross-sectional study. Through a systematized database of 3.5 million affiliates to the Colombian health system, patients with uninterrupted dispensing of anti-dementia drugs between August-October/2016 were selected. Sociodemographic, pharmacological and comedication variables were analyzed. The costs of the therapies were estimated from the reference price of the medicines. RESULTS: We identified 8372 patients with a mean age of 79.5 ± 8.7 years and 65.3% (n = 5471) were women. The most widely used medication was rivastigmine (69.6%), mainly in transdermal presentation, followed by memantine (31.4%). In general, the average dose administered per day was lower than the defined daily dose. Only 568 patients (6.7%) used combination therapy. 84.3% of patients (n = 7061) used some additional medication and 54.2% (n = 4535) had another neurologic medication. The cost per 1000 inhabitants/day of rivastigmine was 3.47 USD and for memantine 0.30 USD. CONCLUSION: Patients with anti-dementia drugs are using them at doses lower than those defined and they present an important frequency of comorbidities and comedications.

TITLE: Patrones de uso de farmacos antidemencia en un grupo de pacientes de Colombia.Introduccion. Los beneficios del manejo farmacologico con medicamentos antidemencia aun no estan del todo demostrados, e incluso hay carencia de trabajos que describan su perfil de utilizacion. El presente trabajo busco determinar los patrones de prescripcion de farmacos antidemencia en una poblacion de Colombia. Pacientes y metodos. Estudio descriptivo de corte transversal. Mediante una base de datos sistematizada de 3,5 millones de afiliados al sistema de salud colombiano, se selecciono a pacientes con dispensaciones ininterrumpidas de farmacos antidemencia entre agosto y octubre de 2016. Se analizaron variables sociodemograficas, farmacologicas y comedicaciones. Se estimaron los costes de las terapias a partir del precio de referencia de los medicamentos. Resultados. Se identifico a 8.372 pacientes con una edad media de 79,5 ± 8,7 años; el 65,3% (n = 5.471) fueron mujeres. El farmaco mas utilizado fue la rivastigmina (69,6%), principalmente en presentacion transdermica, seguida de la memantina (31,4%). En general, la dosis media administrada por dia fue inferior a la dosis diaria definida. Solamente 568 pacientes (6,7%) usaron terapia combinada. El 84,3% de los pacientes (n = 7.061) uso medicamentos para alguna comorbilidad y el 54,2% (n = 4.535) tenia otro neurofarmaco. El coste por 1.000 habitantes/dia de la rivastigmina fue de 3,47 dolares, y de la memantina, de 0,30 dolares. Conclusion. Los pacientes con medicamentos antidemencia los estan empleando en dosis inferiores a las definidas y presentan una importante frecuencia de comorbilidades y comedicaciones.

Patterns of DNA copy number changes in sentinel lymph node breast cancer metastases.

The sentinel lymph node (SLN) is considered to be the first axillary node that contains malignant cells in metastatic breast tumors, and its positivity is currently used in clinical practice as an indication for axillary lymph node dissection. Therefore, accurate evaluation of the SLN for the presence of breast metastatic cells is essential. The main aim of our study is to characterize the genomic changes present in the SLN metastatic samples with the ultimate goal of improving the predictive value of SLN evaluation. Twenty paired samples of SLN metastases and their corresponding primary breast tumors (PBT) were investigated for DNA copy number changes using comparative genomic hybridization (CGH). Non-random DNA copy number changes were observed in all the lesions analyzed, with gains being more common than losses. In 75% of the cases there was at least one change common to both PBT and SLN. The most frequent changes detected in both lesions were gains of 1pter-->p32, 16, 17, 19, and 20 and losses of 6q13-->q23 and 13q13-->q32. In the PBT group, alterations on chromosomes 1, 16, and 20 were the most frequent, whereas chromosomes 1, 6, and 19 were the ones with the highest number of changes in the SLN metastatic group. A positive correlation was found between the DNA copy number changes per chromosome in each of the groups. Our findings indicate the presence of significant DNA copy number changes in the SLN metastatic lesions that could be used in the future as additional markers to improve the predictive value of SLN biopsy procedure.

Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival.

Glioblastomas (GBMs) are resistant to current therapy protocols and identification of molecules that target these tumors is crucial. Interaction of secreted heat-shock protein 70 (Hsp70)-Hsp90-organizing protein (HOP) with cellular prion protein (PrP(C)) triggers a large number of trophic effects in the nervous system. We found that both PrP(C) and HOP are highly expressed in human GBM samples relative to non-tumoral tissue or astrocytoma grades I-III. High levels of PrP(C) and HOP were associated with greater GBM proliferation and lower patient survival. HOP-PrP(C) binding increased GBM proliferation in vitro via phosphatidylinositide 3-kinase and extracellular-signal-regulated kinase pathways, and a HOP peptide mimicking the PrP(C) binding site (HOP230-245) abrogates this effect. PrP(C) knockdown impaired tumor growth and increased survival of mice with tumors. In mice, intratumor delivery of HOP230-245 peptide impaired proliferation and promoted apoptosis of GBM cells. In addition, treatment with HOP230-245 peptide inhibited tumor growth, maintained cognitive performance and improved survival. Thus, together, the present results indicate that interfering with PrP(C)-HOP engagement is a promising approach for GBM therapy.

April 2001: a 70 year old woman with recurrent meningioma.

The April Case of the Month (COM). The contributors report a case of a 70 year-old woman with recurrent meningiomas, one of which showed rhabdoid and lipomatous differentiation. Histopathological study of the first and second previous resections showed only typical meningothelial meningioma. On the third craniotomy, a new tumor specimen showed an admixture of classic meningothelial meningioma with lipomatous and rhabdoid foci. Immunohistochemical studies showed diffuse reactivity for epithelial membrane antigen and vimentin, as well as focal positivity for desmin and smooth muscle actin in the areas with rhabdoid features and S100 protein in the lipomatous foci. The presence of these three different and concomitant histological patterns only in the third surgical resection might support a metaplastic origin and, also, corroborates the concept that rhabdoid features are suggestive of an aggressive behavior.

Iatrogenic Wernicke's encephalopathy in allogeneic bone marrow transplantation: a study of eight cases.

Wernicke's encephalopathy (WE) is a neuropsychiatric condition generally caused by acute thiamine deficiency and classically involves the triad of altered mentation, ataxia and ophthalmoplegia. It is most common among alcoholics, but several other causes have been identified, including total parenteral nutrition (TPN) use. We present eight cases of WE in patients undergoing allogeneic BMT, where thiamine deficiency was caused by a lack of vitamin supplementation during TPN administration. Clinically, WE presented as a severe refractory metabolic acidosis, preceded by 'raspberry tongue', and ophthalmologic and neurologic dysfunction. The sites most affected were the periventricular structures and the thalamus, and no mammilary bodies lesions were found.

Neuropathological findings after bone marrow transplantation: an autopsy study of 180 cases.

We prospectively evaluated the neuropathological complications of 180 patients who underwent autopsy studies following bone marrow transplantation (BMT) (177 allogeneic, three autologous). The most frequent underlying disorders included severe aplastic anemia (n = 55), chronic myelogenous leukemia (n = 53), acute myelogenous leukemia (n = 24) and Fanconi anemia (n = 16). There were 114 males and 66 females. Neuropathological findings were detected in 90.55% of the patients. The most frequent findings were subarachnoid hemorrhages (SAH) (n = 57), intraparenchymal hemorrhages (IHP) (n = 49), fungal infections (n = 16), Wernicke's encephalopathy (n = 10), microglial nodular encephalopathy (n = 10) and neurotoxoplasmosis (n = 8). In only 17 patients was the brain within normal limits. Survival time after BMT averaged 5.4 months and the majority of patients died in the first 3 months post BMT (n = 105). Central nervous system (CNS) pathology was the main cause of death in 17% of the patients (n = 31), with a predominance of IHP in this particular group. Furthermore, the survival time of these patients who died of CNS causes (96.3 days) was almost half of the survival time of those who died of extra-cerebral causes (177.8 days) (P = 0.0162). IHP (70. 96 vs27.22%) (P < 0.001), fungal infections (25.8 vs 8.88%) (P < 0. 001) and toxoplasmosis (9.67 vs 4.44%) (P < 0.001) were significantly more frequent in the group of patients who died due to CNS causes than in the control group. The findings of this work provide a possible guide to the possible causes of neurological syndromes following BMT. Bone Marrow Transplantation (2000) 25, 301-307.

Disseminated Fusarium sp. infection affecting the brain of a child after bone marrow transplantation.

A case of Fusarium sp. infection of the brain in a 6-year-old child who underwent allogeneic BMT is reported. As far as the authors know, this is the first report of Fusarium sp. encephalitis in a BMT patient. Fusarium sp. infection is a rare but emerging fungal pathogen after BMT and, because of several similarities, it is often mistaken for other mold infections, such as Aspergillus sp. The importance of early identification of this fungus as a cause of disseminated fungal infection in BMT patients, and some new modalities of Fusarium sp disseminated infection treatment are discussed here.

Intracranial hemorrhage following bone marrow transplantation: an autopsy study of 58 patients.

Autopsy files of 180 patients were reviewed, who died after BMT between July 1987 and June 1998 and 58 (32.2%) cases, who had experienced intracranial hemorrhage (ICH) were selected. Age, sex, underlying disease, preparatory regimens, immunoprophylaxis, chronic and acute GVHD, survival of the patients and localization and size of hemorrhages were evaluated. There were 33 males and 25 females, with a mean age of 23.4 years. The main underlying disorders for which BMT was performed included SAA (n = 21), CML (n = 13) and AML (n = 10). Forty patients were found to have intraparenchymal hemorrhage, 35 had subarachnoid hemorrhage and eight patients had subdural hemorrhage. In 16 cases the CNS hemorrhage was so extensive that it was considered to be the main cause of death. There was no significant statistical difference concerning sex (P = 0.217), age (P = 0.296), underlying disease (P= 0.352), preparatory regimens (P = 0.07), immunoprophylaxis (P = 0.914), chronic and acute graft-versus-host disease (P = 0.107 and P = 0.631, respectively) and survival (P = 0.701) when comparing patients with or without ICH. However, the number of cases in which the CNS was defined as the main cause of death was higher among patients with ICH than in patients without ICH (n = 16 vs 15) (P = 0.011). We conclude that ICH is common and has a significant mortality rate following BMT.

Ultrastructural study of the neovagina following the utilization of human amniotic membrane for treatment of congenital absence of the vagina.

We present an ultrastructural study of the utilization of human amniotic membrane in the treatment of congenital absence of the vagina in 10 patients. All patients were surgically treated with application of an amniotic membrane graft using the modified McIndoe and Bannister technique. Sixty days after surgery, samples of the vaginal neoepithelium were collected for transmission electron microscopy analysis. The ultrastructural findings consisted of a lining of mature squamous epithelium indicating the occurrence of metaplasia of the amniotic epithelium into the vaginal epithelium. The cells were arranged in layers as in the normal vaginal epithelium, i.e., superficial, intermediate and deep layers. There were desmosomes and cytoplasmic intermediate cytokeratin filaments, as well as some remnant features of the previous amniotic epithelium. These findings suggest that human amniotic membrane is able to complete metaplasia into squamous cells but the mechanism of this cellular transformation is unknown.

Pleomorphic xanthoastrocytoma: report of a case diagnosed by intraoperative cytopathological examination.

The authors present an unusual case of a 13-yr-old boy with a 3-mo history of seizures. A CT scan showed a contrast-enhancing mass located in the left temporal lobe. The patient underwent a stereotatic-guided craniotomy; intraoperative cytological diagnosis was performed by the smear technique, showing a pleomorphic xanthoastrocytoma. The tumor was totally resected. Definitive diagnosis was established by examination of paraffin-embedded material. Six months after the surgical intervention, the patient is doing well, with no radiological evidence of recurrence. The cytological differential diagnosis of giant cell lesions of the central nervous system is emphasized.

Accuracy of the smear technique in the cytological diagnosis of 650 lesions of the central nervous system.

The authors analyzed the results of 650 lesions of the central nervous system submitted to intraoperative cytological diagnosis by the smear technique. Cytological and paraffin section diagnoses were compared. The following statistical values were obtained: accuracy of 97.3%, sensitivity of 97.9%, specificity of 95%, positive predictive value of 99.1%, and negative predictive value of 89.6%. The authors comment on their main pitfalls using this cytological diagnostic procedure.

Smear technique for the intraoperative examination of nervous system lesions.

To evaluate the accuracy of the smear technique in the rapid diagnosis of lesions of the central and peripheral nervous system, intraoperative diagnoses made on cytologic preparations in 307 consecutive cases were compared with the final paraffin section diagnoses. In 92.2% of cases the final diagnosis obtained on paraffin preparations was similar to that made on smears. In this group there were neuroglial tumors, meningiomas and medulloblastomas, among others. In the cases in which the cytologic diagnoses were not confirmed by paraffin sections, the majority of the cases were unlikely to affect immediate neurosurgical management, while in only 0.7% of all cases (n = 2) an incorrect smear diagnosis might have affected the neurosurgical procedure. The cytologic diagnostic criteria are discussed together with the main difficulties in interpretation with this valuable approach to a rapid neurosurgical diagnosis.

Value of fine needle aspiration in the diagnosis of breast lesions.

OBJECTIVE: To evaluate the accuracy values of 276 fine needle aspriations (FNA) of breast lesions with a subsequent excisional biopsy diagnosis and to make a comparison between 25 studies of the literature using the same criteria to calculate those values. STUDY DESIGN: Cytologic findings were compared with the histologic diagnosis of each mass. The correlation of results was analyzed by a decision-analysis approach, and the following values concerning diagnostic accuracy were calculated in the present study and in 25 other reports: sensitivity, specificity, positive predictive value, negative predictive value, false positive fraction and false negative fraction. To calculate those values, we eliminated unsatisfactory results and assumed that suspicious and positive cytologic findings represented carcinoma of the breast. RESULTS: Comparing our results with the means in the literature (numbers in parenthesis), FNA detected cancer with a sensitivity of 92.1% (87.7%), specificity of 98.6% (94.7%), positive predictive value of 99.4% (92.8%), negative predictive value of 82.1% (90.7%), false positive fraction of 0.6% (7.1%) and false negative fraction of 17.9% (13.4%); in 6.2% of cases the material was unsatisfactory (13.4%). CONCLUSION: All the rates varied enormously between the studies and during the past 13 years. It seems that false positive and false negative fractions tended to diminish and stabilize in more recent years, and specificity and sensitivity underwent a slight increase. The differences between the rates of those studies suggest that FNA of the breast has some unavoidable limitations.

Peritoneal effusion in a dog secondary to visceral mast cell tumor. A case report.

BACKGROUND: Mast cell tumor, one of the most common skin tumors in dogs, may also be found in visceral sites (mainly spleen and liver). When a visceral mast cell tumor is present, neoplastic mast cells may be found in any effusion secondary to the tumor. Therefore, the diagnosis may be made by cytologic analysis of the effusion. CASE: An 8-year-old, spayed, female Siberian husky presented with a peritoneal effusion secondary to a visceral mast cell tumor. Seven months earlier, the dog had presented with a cutaneous nodule diagnosed as a well-differentiated mast cell tumor. The peritoneal fluid was classified as a transudate. Numerous neoplastic mast cells were found in the effusion. Although the mast cell tumor presented with characteristics of the well-differentiated tumor, its biologic behavior was that of a malignant tumor. CONCLUSION: Care should be taken to evaluate the prognosis of mast cell tumors in dogs since their biologic behavior is extremely variable.

[Clinical practice guidelines of the Spanish Society of Cardiology for surgical risk assessment in cardial patients treated with non-cardiac surgery]. / Guías de práctica clínica de la Sociedad Española de Cardiología en la valoración del riesgo quirúrgico del paciente cardiópata sometido a cirugía no cardíaca.

All patients undergoing a surgical intervention require a cardiovascular evaluation that establishes the surgical risk. On the other hand, an important proportion of the deaths that happened during the surgery are due to cardiovascular complications, many of them could be avoided with a cardiac risk screening. The surgery and the anesthesia subject the patient to stress situations during the perioperative period that forces the check upon capacity of the patient to respond to those demands, dissuading surgery if it considered that the risk is very high. The rate of major surgery in elderly patients is growing, with the increase in cardiovascular complications, mainly myocardial infarction, unstable angina and perioperative heart failure. Following we establish some recommendations for the cardiovascular assessment of the cardiac patient that will undergo noncardiac surgery.

[Neuromuscular junction changes in experimental myopathies in mice]. / Alterações da junção neuromuscular em miopatias experimentais no camundongo.

Morphological abnormalities of the neuromuscular junction in two murine models with primary myopathy were studied by combined cholinesterase-silver impregnation techniques and electron microscopy. In both situations the results were similar showing that the neuromuscular junction remained unaffected even when innervating necrotic muscle fibres. In regenerated muscle fibres, however, there was marked simplification of the post-synaptic membrane with reduction in number and depth of folds up to 50% of normal values confirmed by morphometric analysis. Since after regeneration succeeded no detectable clinical or physiological alterations were observed in these experiments it seems reasonable to assume that the prominent branching of post-synaptic folds in normal skeletal muscles might represent an increased anatomical safety mechanism in chemical transmission.

Inherited neuromuscular diseases in the mouse. A review of the literature.

There are several neuromuscular disorders affecting the human being. Most of these are poorly understood and lack and effective treatment. Due to the limitation of experimental manipulation in "anima nobili", inherited neuromuscular diseases in laboratory animals constitute a valuable source of scientific information. Amongst several animal species affected by neuromuscular disorders the house mouse is of particular interest because of its small size, short pregnancy and low costs of maintanence. In the present review 20 murine mutants with diseases affecting peripheral nerves, skeletal muscles and motor end-plates are tabulated. Genetic, clinical and pathological aspects are discussed aiming to provide information about these mutants which might be of great interest as animal models for human neuromuscular diseases.

[Cytopathologic diagnosis of neuroepithelial tumors by the smear technique]. / Diagnóstico citopatológico de tumores neuroepiteliais pela técnica do esfregaço.

We studied 198 cases of neuroepithelial tumours with intra-operative diagnosis made by smears comparing the accuracy rates with the final paraffin section diagnosis. In 90.6% of cases the final diagnosis obtained on paraffin preparations was similar to that made on smears. In the group of cases with cytological diagnosis not confirmed by paraffin sections the majority of cases were unlike to affect immediate neurosurgical management, and represent mainly differences in grading of astrocytomas and mixed gliomas. The cytological diagnostic criteria are discussed together with the main difficulties for the interpretation of this valuable approach to intra-operative neurosurgical diagnosis.