CSF analysis for protein biomarker identification in patients with leptomeningeal metastases from CNS lymphoma.

INTRODUCTION: Leptomeningeal metastases (LM) from lymphoma remain a difficult complication for oncologist due to the high incidence in morbidity and mortality. Early diagnostic and initiation of treatment are essential to prevent neurological deterioration. Areas covered: In this review, several proteomic approaches are described in order to help and provide the basis for the identification of biomarkers useful in early diagnosis, also in discovery novel targets for therapeutic agents. In fact, the identification of biomarkers will have a high potential to detect leptomeningeal lymphoma, as well as to predict its progression and treatment response. Expert commentary: In the case of LM by Central nervous system (CNS) lymphoma, these studies generated the first insights into the utility of proteomic analysis for biomarker identification and will be demonstrated that identifying specific proteins in cerebrospinal fluid (CSF) had much greater sensitivity for detecting LM in comparison to standard cytological protocols.

Pharmacogenetic studies in Alzheimer disease.

INTRODUCTION: Alzheimer disease (AD) is the most common cause of dementia and is considered one of the main causes of disability and dependence affecting quality of life in elderly people and their families. Current pharmacological treatment includes acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine; however, only one-third of patients respond to treatment. Genetic factors have been shown to play a role in this inter-individual variability in drug response. DEVELOPMENT: We review pharmacogenetic reports of AD-modifying drugs, the pharmacogenetic biomarkers included, and the phenotypes evaluated. We also discuss relevant methodological considerations for the design of pharmacogenetic studies into AD. A total of 33 pharmacogenetic reports were found; the majority of these focused on the variability in response to and metabolism of donepezil. Most of the patients included were from Caucasian populations, although some studies also include Korean, Indian, and Brazilian patients. CYP2D6 and APOE are the most frequently studied biomarkers. The associations proposed are controversial. CONCLUSIONS: Potential pharmacogenetic biomarkers for AD have been identified; however, it is still necessary to conduct further research into other populations and to identify new biomarkers. This information could assist in predicting patient response to these drugs and contribute to better treatment decision-making in a context as complex as ageing.

Pharmacogenetic studies in Alzheimer disease. / Estudios farmacogenéticos en la enfermedad de Alzheimer.

INTRODUCTION: Alzheimer disease (AD) is the most common cause of dementia and is considered one of the main causes of disability and dependence affecting quality of life in elderly people and their families. Current pharmacological treatment includes acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine; however, only one-third of patients respond to treatment. Genetic factors have been shown to play a role in this inter-individual variability in drug response. DEVELOPMENT: We review pharmacogenetic reports of AD-modifying drugs, the pharmacogenetic biomarkers included, and the phenotypes evaluated. We also discuss relevant methodological considerations for the design of pharmacogenetic studies into AD. A total of 33 pharmacogenetic reports were found; the majority of these focused on the variability in response to and metabolism of donepezil. Most of the patients included were from Caucasian populations, although some studies also include Korean, Indian, and Brazilian patients. CYP2D6 and APOE are the most frequently studied biomarkers. The associations proposed are controversial. CONCLUSIONS: Potential pharmacogenetic biomarkers for AD have been identified; however, it is still necessary to conduct further research into other populations and to identify new biomarkers. This information could assist in predicting patient response to these drugs and contribute to better treatment decision-making in a context as complex as aging.

In vitro and in vivo Methods for the Evaluation of Natural Products against Dermatophytes.

Dermatomycoses are infections caused by fungi called dermatophytes; these affect 20-25% of the world population and the incidence continues to grow each year. Recently, an alternative for the treatment of these diseases is the use of natural products, thanks to the fact that they possess great chemical diversity and thus biological activity. However, to understand the therapeutic potential of natural products, their microbiological assessment presents certain limitations. Currently, there is no established reference method to determine the antifungal capacity in vitro and in vivo of natural products (i.e., essential oils). This review focuses on describing the various microbiological methods as well as the many adaptations used to evaluate the antifungal activity of natural products both in vitro and in vivo. In addition, the antifungal evaluation of natural products formulated in creams, gels, nanoemulsions, nanocapsules and solid lipid nanoparticles is included.

[THE INFLUENCE OF THE POLYUNSATURATED FATTY ACIDS IN THE PREVENTION AND PROMOTION OF CANCER]. / INFLUENCIA DE LOS ÁCIDOS GRASOS POLIINSATURADOS EN LA PREVENCIÓN Y PROMOCIÓN DEL CÁNCER.

INTRODUCTION: each year, almost eight million people die in the world due to cancer. Carcinogenesis is a process that involves a series of structural alterations of the DNA which affect its stability and prevents proper cell reproduction and development. There are many factors that influence the cancer etiology. Nutritional factors are included among them. The polyunsaturated fatty acids (PUFA) intake is associated more and more with the prevention and development of chronic diseases with an inflammatory component such as cancer. OBJECTIVE: this work reviews the latest bibliography on the PUFA and its relationship with the cancer, mainly of prostate, breast and colon cancer. METHODS: the preliminary search resulted in 92 selected references. But, after their review, 40 experimental studies, in animals and in vitro, and epidemiological studies have been included. RESULTS: experimental studies in animals and in vitro reviewed show a protective effect of ω3 PUFA against cancer. However, human studies are contradictory; although it is clear there is evidence of the protective effect of the ω3 PUFA in colon cancer prevention. CONCLUSION: the relationship between ω6 and ω3 PUFA of the diet against the cancer risk is becoming increasingly important, but further studies are needed to confirm their influence on the development of this disease.

Introducción: alrededor de ocho millones de personas mueren anualmente en el mundo debido al cáncer. La carcinogénesis es un proceso que conlleva, entre otras, una serie de alteraciones de la estructura del ADN, afectando su estabilidad e impidiendo la correcta proliferación celular. Son muchos los factores que influyen en la etiología del cáncer. Dentro de dichos factores están los nutricionales. La ingesta de ácidos grasos poliinsaturados (AGPI) se relaciona cada vez más con la prevención y el desarrollo de enfermedades crónicas con un componente inflamatorio, como el cáncer. Objetivo: revisar la bibliografía más reciente de los últimos cinco años sobre la ingesta de AGPI y su relación con el cáncer, principalmente de próstata, mama y colon, para concretar la posible existencia de una evidencia científica concluyente al respecto. Método: la búsqueda preliminar en la literatura proporcionó 92 referencias. Finalmente, tras su revisión, se han incluido 40 estudios directamente relacionados, conformados por estudios experimentales, en animales e in vitro, así como estudios epidemiológicos. Resultados: los estudios experimentales en animales e in vitro revisados concluyen un efecto protector de los AGPI omega-3 frente al cáncer. Sin embargo, los estudios en humanos son contradictorios, aunque sí parece existir una clara evidencia del efecto protector de los AGPI 3 en la prevención del cáncer de colon. Conclusión: la relación entre AGPI 6 y AGPI 3 de la dieta frente al riesgo de padecer cáncer cobra cada vez más importancia, si bien se necesitan más estudios para confirmar su influencia en el desarrollo de esta enfermedad.

Cryptic 6q subtelomeric deletion associated with a paracentric inversion in a mildly retarded child.

We report on a girl with minor anomalies and developmental delay carrying an apparently balanced paracentric inversion of chromosome 6q (q22qter). Fluorescent in situ hybridization analysis demonstrated a deletion of the subtelomeric region of 6q. This illustrates the use of specific subtelomeric fluorescent in situ hybridization probes to detect cryptic deletions as an important cause of mental retardation in seemingly balanced chromosome rearrangements.

Two new cases of Cumming syndrome confirming autosomal recessive inheritance.

We report on two stillborn sisters with generalized hydrops, campomelia, cervical lymphocele, and polycystic dysplasia of kidney, liver, and pancreas. This syndrome conforms to that first described by Cumming et al. [Am. J. Med. Genet. 25:783-790, 1986]. This observation provides additional support for the notion that this syndrome has an autosomal recessive pattern of inheritance.

Uptake of GABA by bovine adrenal medulla slices.

A sodium dependent GABA uptake system has been found in bovine adrenal medulla slices. This uptake has a Km of 83.19 +/- 38.45 microM and a Vmax of 9.20 +/- 1.36 pmol/min X mg of tissue. It was inhibited by nipecotic acid and 2,4-diaminobutyric acid (IC50 67 and 38.5 microM, respectively) but not by beta-alanine at concentrations up to 5 mM, a result which is similar to those found for the neuronal GABA uptake rather than the glial uptake. It is suggested that GABA uptake together with catabolic action of GABA-transaminase, also found in this tissue, could be regulating the GABA levels disposable for the proposed modulator role on catecholamine secretion of this amino acid in adrenal medulla.

Ser186Pro mutation of RHO gene in a Spanish autosomal dominant retinitis pigmentosa (ADRP) family.

A Spanish family affected with autosomal dominant retinitis pigmentosa (ADRP) with a diffuse phenotype showed a mutation in the rhodopsin gene. The mutation was the transition T-->C in codon 186, which has been reported once before in an American patient (Dryja et al., Proc Natl Acad Sci USA 1991;88:9370-9374). This change replaces a serine by a proline in the second intradiscal loop of the protein, generating a molecule that is probably folding- and transport-defective.

Quantification of bovine albumin fraction V in cellular antigens of antileptospirosical Cuban vaccine vaxSpiral.

A solid phase immunoradiometric assay (IRMA) for quantification of bovine albumin fraction V (Bov.Alb.FV) in antileptospirosical Cuban vaccine vaxSpiral is described in the present work. Anti-Bov.Alb.FV IgG raised against rabbit purified by affinity chromatography was used as first antibody. Anti-rabbit IgG labeled by Chloromine-T reaction was used as a tracer and the method has demonstrated to be sensitive with high intra- and inter-assay reproducibility. Eight lots of vaccinal antigens were evaluated and in all of the cases, the bovine albumin fraction V concentration was lower than 1 microgram/mL, as the World Health Organization (WHO) establishes. This IRMA is a simple and sensitive assay and could be used as control method for all human vaccines that use Bov.Alb.FV in their production process, even cellular vaccines.

[An intimal sarcoma of the pulmonary artery. An immunohistochemical study]. / Sarcoma intimal de la arteria pulmonar. Estudio inmunohistoquímico.

Pulmonary artery intimal sarcomas tend to be presented with symptoms of pulmonary thromboembolism and grow regionally, with little capacity to metastasize. They probably originate from subendothelial cells, that become myofibroblasts. Knowledge of it is important to establish a presurgery diagnosis, with the possibility of a total resection, the only useful treatment until now. We report a case of a pulmonary artery primary sarcoma, in a 73 year old woman, admitted with hemoptysis and pleuritic chest pain, who died ten days after. Autopsy revealed an intraluminal mass at the pulmonary artery trunk, without regional nor distance involvement. Microscopic study showed a pleomorphic tumor with spindle and epithelioid cells, positive for actin, desmin and vimentin. All these data support the diagnosis of primary intimal sarcoma of the pulmonary artery. We want to emphasize the myogenic differentiation of the tumor, uncommon in previously reported cases.

[Maze technique for the treatment of auricular fibrillation: initial experience]. / Técnica de MAZE para el tratamiento de la fibrilacion auricular: experiencia inicial.

INTRODUCTION AND OBJECTIVES: The MAZE procedure was developed as a surgical approach to the management of patients with atrial fibrillation refractory to medical treatment. This study seeks to identify the risk and benefits of adding the MAZE procedure in patients with atrial fibrillation undergoing surgery for underlying organic cardiac disorders. MATERIAL AND METHODS: Since november 1993, we have performed 10 interventions with the MAZE procedure, for the treatment of refractory atrial fibrillation. The indication to perform the technique was systemic embolism in 5 patients, contraindication for the anticoagulant treatment in two cases and no response to antiarrhythmic treatment in 5 cases. Two patients had more than one indication. In all the cases another surgical procedure was performed, 5 replacements of mitral valve, a mitral repair, one tricuspid repair and tree repairs of an atrial septal defect. RESULTS: Soon after surgery 9 patients were in sinus rhythm, and one in atrial fibrillation. Four patients needed atrial pacing during the first days. One patient required a pacemaker due to symptomatic sinus bradycardia. During the first 3 months, 4 patients had episodes of paroxysmal atrial fibrillation and flutter. One patient died suddenly one month after surgery. Seven patients have completed two years of follow-up, and are in stable sinus rhythm, in functional class I and free of antiarrhythmic drugs. All of them have echocardiographic evidence of mechanical activity in both atria. Left atrium had been reduced from 5.3 +/- 0.7 cm to 4.5 +/- 0.7 cm (p < 0.05). No patient has presented new embolic events. CONCLUSIONS: The MAZE procedure is a good choice in selected patients with atrial fibrillation refractory to medical treatment, or a precedent of systemic embolism. However, several problems can complicate the patient's course.

[The mechanisms of satiation]. / Mecanismos de saciedad.

There are many published experimental studies which attempt to explain certain aspects of satiety, but only very few treat this problem as a whole, synthesizing concepts. At present, the understanding of the mechanisms of satiety is extremely interesting for the study and application of medical or surgical anti-obesity treatments.

[Endocrine metabolic and arterial pressure changes in morbidly obese patients treated with vertical gastroplasty]. / Modificaciones endocrino-metabólicas y de la presión arterial en obesos morbidos tratados mediante gastroplastia vertical.

When overweight surpasses 100% of the ideal weight, morbid obesity, the obese patients is condemned to a complete inability to work, social and sexual inability, and shall suffer from an increase in its morbidity and mortality. This depends to a large degree on the additions to the obesity of insulin resistance, carbohydrates intolerance, hypertriglyceridemia, hypercholesterolemia, and arterial hypertension, all of which is enveloped in a atmosphere of neuroendocrine alterations. An efficient method of treating this syndrome is weigh loss. Medical treatments have not achieved prolonged weight losses during long periods in morbid obese patients, which is a reason for surgery to try and propose new lines of treatment for these patients. The purpose of our study is to examine the effect of weight loss in 100 patients treated with vertical gastroplasty, on the metabolic disorders (triglycerides, cholesterol, glucose) and the arterial hypertension, which are considered to be risk factors in the mortality associated with morbid obesity. Our results indicate that the weight loss modified the metabolic conditions of the patients, with there being a decrease of the levels of triglycerides, cholesterol, glucose, and arterial pressure, after 6 to 12 months after the weigh loss.

[The fundus oculi in the hemiplegic patient]. / El fondo de ojo en el paciente hemipléjico.

INTRODUCTION AND OBJECTIVE: The fundus oculi is useful for observation of the interior of the eye and the retina. This study establishes a relationship between patients with established cerebral infarcts and the results observed in their fundi. PATIENTS AND METHODS: A retrospective study of the clinical histories of 177 patients seen in the rehabilitation department over a period of one year. RESULTS: The patients were aged between 29 and 85 years. The majority were men; 101 patients (57.06%) had systolic-diastolic arterial hypertension. On study of the fundus oculi there was a predominance of alterations of the blood vessels of the retina due to vascular sclerosis (93.1%) but only 24.4% had frank alterations caused by arterial hypertension. CONCLUSIONS: We found a slight relation between arterial hypertension and the alterations observed in the fundus oculi of these patients.

[MEN I (multiple endocrine neoplasia): patient screening and new tumor markers]. / MEN I: Screening de pacientes y nuevos marcadores tumorales.

Multiple endocrine neoplasia type I (men I) associates hyperparathyroidism with pancreatic tumors. The evaluation included the patient and its family, periodically. A good patient medical history, biochemical blood tests, carried out regularly and in an organised fashion, brings to the fore the diagnosis without difficulties. Tumoral markers are now being considered an important test for diagnosis and follow-up (gastrin, pancreatic peptid, prolactin...). The newest chromogranin is a polypeptidic group which increases in the blood of patients with endocrine neoplasias (including hyperparathyroidism and tumors of pancreatic islet cells). The specific neural enolase is increase in pancreatic islet cells tumor. The evaluation of S-100 substance, 7-B2 protein, neurotensin, alpha sub-unit of chorionic gonadothrophin and other markers will soon be of help in the diagnosis of men I.

[Graves' disease with associated thyroid nodules (nodular Graves' disease). Clinical, diagnostic and therapeutic considerations]. / Enfermedad de Graves-Basedow con nódulos tioideos asociados (enfermedad de Graves-Basedow nodular). Consideraciones clínicas, diagnósticas y terapéuticas.

BACKGROUND: Sometimes Graves disease (GD) can appear in association with thyroid nodules, which seems to increase the risk of carcinoma. In this article, we try to establish clinical characteristics, diagnostic means and appropriate treatment for Graves patients with co-existent nodules. METHOD: A retrospective study was made of 153 consecutive patients who underwent operation for GD between 1967 and 2000. Each patient was subject to a regular protocol including physical examination, diagnostic test, total or subtotal thyroidectomy and follow-up in the long term with the purpose of making a valuation of the postsurgical morbidity, evolution and relapses. Data were processed through computing in order to get the statistical information. RESULTS: 28.1% of GD had thyroid nodules and carcinoma was diagnosed in four patients (9.3%), all of them belonging to papillary variety. Surgery consisted of 57 subtotal thyroidectomies (37.3%) and 94 total thyroidectomies. Parathyroid and recurrent morbidity was established in 4.6 and 3.9%, respectively, a year later since the operation, though it had a strong tendency to decrease from 1980. 96% of cases showed no relapse. CONCLUSIONS: Nodular GD is very common in our setting, especially in Graves patients with late beginning who wait for ages until they are undergone surgery. Initial treatment should be by means of braking therapy with antithyroid drugs and clinical, cytologic and ultrasonographic control. Surgery would be advised, from the outset or during the follow-up, in view of either any suspicion about cancer or presence of local growth. The procedure of choice is total thyroidectomy performed with low morbidity.

[Acute ++indomethacin-induced hepatitis in a female patient with asymptomatic primary biliary cirrhosis]. / Hepatitis aguda por indometacina en una enferma con cirrosis biliar primaria asintomática.

We present an infrequent case of acute hepatitis by indomethacin, in a patient with a primary biliary cirrhosis, previously not diagnosed and asymptomatic, in who during in the follow-up, with a persistent analytical pattern of disociated cholestasis, a liver biopsy was indicated, with the final diagnosis of chronic non-suppurative destructive cholangitis.

[Miliary tuberculosis. Autopsy study of 29 cases]. / Tuberculosis miliar. Estudio autópsico de 29 casos.

A retrospective anatomoclinic study of 29 cases of miliary tuberculosis, selected from 2.808 necropsies carried out at Hospital Central de Asturias between 1971 and 1994, is described. Fifty eight per cent of the patients were older than 50 years. Predisposing factors were identified in 80%: diabetes, alcoholism, chronic hepatopaty, silicosis, chronic renal failure, immunessupresive treatment and malignant neoplasms. A premorten correct clinical diagnosis were done in 8 cases (27.5%) and were suspected in 4 (13.7%). Typical miliary radiologic pattern was established in 17%. The more frequently affected organs were lungs (100%), liver (82%), spleen (75%), lymphatic nodes (55%) and bone marrow (41%). Early diagnosis and treatment is nowadays more difficult because of increasing of cryptic tuberculosis, involvement of resistant organs (pancreas), new predisposing factors (chronic renal failure), new risk groups (AIDS) and lack of demonstrative clinical and radiologic findings, so is necessary to maintain suspect of this disease always in mind.