Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study.

BACKGROUND: Andrographis paniculata (A. paniculata), a medicinal plant, has shown anti-inflammatory, neuroprotective and antifibrotic effects in animal models as well as clinical efficacy in different studies, including an anti-fatigue effect in autoimmune diseases such as rheumatoid arthritis. In multiple sclerosis (MS), fatigue is rated as one of the most common and disabling symptoms. In the present trial, we investigated the effect of A. paniculata on relapse rate and fatigue in relapsing-remitting MS (RRMS) patients receiving interferon beta. METHODS: A randomised double-blind placebo-controlled trial assessed the effects of 170 mg of A. paniculata dried extract tablet b.i.d. p.o. on relapse rate and fatigue using the Fatigue Severity Scores (FSS) over 12 months in RRMS patients receiving interferon. The Expanded Disability Status Scale (EDSS) score, inflammatory parameters and radiological findings were also investigated. Twenty-five patients were enrolled, and twenty-two patients were ultimately analysed and randomised to the active or placebo group. RESULTS: Patients treated with A. paniculata showed a significant reduction in their FSS score as compared to the placebo, equivalent to a 44 % reduction at 12 months. No statistically significant differences were observed for relapse rate, EDSS or inflammatory parameters, with a trend in reducing new lesions among the A. paniculata group. One patient in the A. paniculata group presented with a mild and transient skin rash, which was alleviated with anti-histamine treatment for three weeks. CONCLUSION: A. paniculata was well tolerated in patients and no changes in clinical parameters were observed. A. paniculata significantly reduces fatigue in patients with RRMS receiving interferon beta in comparison to placebo and only interferon beta treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02280876 ; Trial registration date: 20.10.2014.

Systemic lupus erythematosus impairs memory cognitive tests not affected by depression.

OBJECTIVE: Our aim was to assess the contribution of depression to cognitive impairment in patients with systemic lupus erythematosus (SLE). METHODS: Clinical features, education, age, and Hospital Anxiety and Depression Scale (HADS) were evaluated in 82 patients with SLE and 22 healthy controls, all Chilean women. The Cambridge Neuropsychological Test Automated Battery (CANTAB eclipseTM) assessing attention, spatial memory, and learning and executive function domains was applied. Cognitive deficit definition: a cut-off for definite impairment was defined as a score below -2 standard deviations in at least one outcome measure in two or more domains. ANCOVA with stepwise selection evaluated influences of health status (SLE or control), age, education, and HADS depression and anxiety scores on cognitive outcomes. To avoid overfitting, a shrinkage method was performed. Also, adjusted p-values for multiple comparisons were obtained. RESULTS: Cognitive deficit affected 16 (20%) patients, and no controls (p=0.039). Median HADS depression score in SLE patients was 6 (range 0-19) and in controls was 0 (0-19), p<0.001). ANCOVA and shrinkage models showed that worse cognitive performance in sustained attention and spatial working memory tests was explained by the presence of SLE but not depression, whereas depression only affected a measure of executive function (I/ED Stages completed). CONCLUSION: Depression has a limited role in cognitive impairment in SLE. Impairments in sustained attention and spatial working memory are distinctly influenced by yet-unknown disease-intrinsic factors.

[Glucose-6-phosphate dehydrogenase deficiency in children: a case report]. / Deficiencia de glucosa 6 fosfato deshidrogenasa en niños: caso clínico.

INTRODUCTION: Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) is the most common red blood cell (RBC) enzyme disorder. The decrease as well as the absence of the enzyme increase RBC vulnerability to oxidative stress caused by exposure to certain medications or intake of fava beans. Among the most common clinical manifestations of this condition, acute hemolysis, chronic hemolysis, neonatal hyperbilirubinemia, and an asymptomatic form are observed. OBJECTIVE: To analyze the case of a child who presented hemolytic crisis due to favism. CASE REPORT: A 2 year and 7 month old boy with a history of hyperbilirubinemia during the newborn period with no apparent cause, no family history of hemolytic anemia or parental consanguinity. He presented a prolonged neonatal jaundice and severe anemia requiring RBC transfusion. An intake of fava beans 48 h prior to onset of symptoms was reported. G6PD qualitative determination was compatible with this enzyme deficiency. CONCLUSION: G6PD deficiency can be highly variable in its clinical presentation, so it is necessary to keep it in mind during the diagnosis of hemolytic anemia at any age.

Socioeconomic, health-care access and clinical determinants of disease severity in Multiple Sclerosis in Chile.

BACKGROUND: MS severity may be affected by genetic, patient-related, disease-related and environmental factors. Socioeconomic status, including income and healthcare access, amongst others, may also have a role in affecting diagnostic delay or therapy prescription. In Chile, two main healthcare systems exist, public-healthcare and private-healthcare, nonetheless universal care laws (e.g., access to High Efficacy Therapy-HET), including both systems, have been recently enacted for people with MS. OBJECTIVE: To assess the role of Socioeconomic Conditions (SEC), clinical variables and public health policies on the impact of disease severity of MS patients in Chile. METHODS: Multicentric, observational, cross-sectional study including patients from two reference centres (1 national reference centre from the private-health system and 1 regional reference centre from the public-health system). SEC and clinical variables included healthcare insurance (private or public), subclassification of health insurance according to monthly income, sex, age at onset, diagnostic delay, disease duration, diagnosis before HET law (as a proxy of HET delay), and current HET treatment. Progression Index (PI), EDSS ≥6.0 and Progressive MS diagnosis were used as outcome measures. Multivariable binary logistic regression was performed. RESULTS: We included 604 patients (460 private-health, 144 public-health), 67% women, 100% white/mestizo, 88% RRMS, mean age 42±12 years, mean age at onset 32±11 years, mean disease duration 10±6 years, median diagnostic delay 0 (0-34) years, 86% currently receiving any DMT, 55% currently receiving HET, median EDSS at last visit of 2.0 (0-10), and median PI 0.17 (0-4.5). Lower monthly income was associated with higher EDSS and higher PI. In the multivariable analysis, public-healthcare (OR 10.2), being diagnosed before HET-law (OR 4.89), longer diagnostic delay (OR 1.26), and older age at onset (OR 1.05) were associated with a higher risk of PI>0.2, while current HET (OR 0.39) was a protective factor. Diagnosis before HET-law (OR 7.59), public-healthcare (OR 6.49), male sex (OR 2.56), longer disease duration (OR 1.2) and older age at onset (OR 1.1) were associated with a higher risk of Progressive MS. Public-healthcare (OR 5.54), longer disease duration (OR 1.14) and older age at onset (OR 1.08) were associated with a higher risk of EDSS ≥6.0 while current treatment with HET had a trend as being a protective factor (OR 0.44, p = 0.05). CONCLUSION: MS severity is impacted by non-modifiable factors such as sex and age at onset. Interventions focused on shortening diagnostic delay and encouraging early access to high-efficacy therapies, as well as initiatives that may reduce the disparities inherent to lower socioeconomic status, may improve outcomes in people with MS.

Refractory epilepsy associated with anti-ribosomal P antibodies successfully treated with topiramate.

We report the case of a 25-year-old woman who developed temporal lobe epilepsy associated with systemic lupus erythematosus (SLE). Serum and cerebrospinal fluid samples showed high titers of anti-ribosomal P (anti-P) antibodies with negative anti-NMDAR antibodies. She was receiving prednisone and azathioprine, with normalization of SLE serum markers, but without changes in titers of anti-P antibodies. No seizure control was achieved using valproic acid, levetiracetam and lamotrigine. However, she had a selective response to topiramate, an AMPAR blocker, maintained during 6 years of follow-up. We discuss the pathophysiology of this autoimmune epilepsy associated with high titer anti-P antibodies.

LGI1-antibody associated epilepsy successfully treated in the outpatient setting.

We report six patients with anti-LGI1 associated epilepsy. Two patients presented with new-onset generalized tonic-clonic seizures, four developed faciobrachial dystonic seizures and two piloerection. All patients had significant cognitive complaints at the time of diagnosis. All patients described seizure reduction during the first week of carbamazepine, and seizure freedom was obtained at a median of 13 days (range 7-22), sustained after the initiation of immunosuppression. Median time from symptom onset to carbamazepine initiation was 164 days (range 38-206 days). We discuss the particular seizure response to sodium channel blocking antiepileptic drugs, alone or associated with immunosuppression in this antibody mediated seizures.

Functional magnetic resonance imaging in the study of multiple sclerosis. / Imagenes de resonancia magnetica funcional en el estudio de la esclerosis multiple.

INTRODUCTION: Multiple sclerosis (MS), a neuroinflammatory and demyelinating disease, modifies the normal connectivity among different brain regions involved in specific functions. Functional magnetic resonance imaging (fMRI), based on local changes in oxygen level as a response to the increase in neural activity, provides an approach to neural connectivity and brain dynamics which give us an overview on visual, motor and cognitive dysfunction and their mechanisms. DEVELOPMENT: An advanced search was performed using PubMed. Terms 'fMRI', 'visual', 'motor', 'cognitive' and 'multiple sclerosis' included in title and abstract were considered. We focus on original articles available in English. Articles were included based on their abstracts, looking for those potentially useful for understanding functional changes in MS. An important amount of studies have used fMRI as a complementary tool in the study of MS and clinically relevant alterations compromising visual, motor and cognitive domains. Since the earliest stages of the disease, local activity, and global neural dynamics appear to be compromised. Even when functional performance is still preserved, a different recruitment of neural resources arises as a compensatory response to disconnection observed in the disease. CONCLUSIONS: The main findings of fMRI applied to MS are strongly related to the demyelinating nature of the disease and provide an adequate insight into the mechanisms that underlie functional alterations reported in this disease. fMRI also appears to be useful for studying disease evolution and response to treatment in MS and other disorders.

TITLE: Imagenes de resonancia magnetica funcional en el estudio de la esclerosis multiple.Introduccion. La esclerosis multiple (EM), una enfermedad neuroinflamatoria y desmielinizante, modifica la conectividad normal entre las diferentes regiones del cerebro involucradas en funciones especificas. La resonancia magnetica funcional (RMf), basada en cambios locales en el nivel de oxigeno como respuesta al aumento de la actividad neuronal, proporciona un enfoque a la conectividad neuronal y la dinamica cerebral que ofrece una vision general de la disfuncion visual, motora y cognitiva y sus mecanismos. Desarrollo. Se realizo una busqueda avanzada en PubMed considerando los terminos 'fMRI', 'visual', 'motor', 'cognitive' y 'multiple sclerosis' incluidos en el titulo y el resumen. La busqueda se centro en articulos originales disponibles en ingles, con enfasis en los utiles para comprender los cambios funcionales en la EM. Numerosos estudios han utilizado la RMf como una herramienta complementaria en el estudio de la EM y las alteraciones clinicamente relevantes de la afectacion visual, motora y cognitiva. Desde las primeras etapas de la EM, la actividad local y la dinamica neural global parecen estar afectadas. Incluso cuando el desempeño funcional aun se conserva, surge un reclutamiento diferente de los recursos neuronales como respuesta compensatoria a la desconexion observada en la enfermedad. Conclusiones. Los principales hallazgos de la RMf aplicada a la EM estan fuertemente relacionados con la naturaleza desmielinizante de la enfermedad y proporcionan una vision adecuada de los mecanismos subyacentes a las alteraciones funcionales. La RMf tambien parece ser util para estudiar la evolucion de la enfermedad y la respuesta al tratamiento en la EM y otros trastornos.

Internet as a tool to access high-risk men who have sex with men from a resource-constrained setting: a study from Peru.

OBJECTIVES: In Peru, current interventions in high-risk men who have sex with men (MSM) reach a limited number of this population because they rely solely on peer education. The objective of this study was to assess the use of the internet as an alternative tool to access this population. METHODS: Two nearly identical banner ads-both advertising an online survey but only one offering free HIV/syphilis tests and condoms-were displayed randomly on a Peruvian gay website. RESULTS: The inclusion of the health incentive increased the frequency of completed surveys (5.8% vs 3.4% of delivered impressions; p<0.001), attracting high-risk MSM not previously tested for HIV but interested in a wide variety of preventive Web-based interventions. Eleven per cent (80/713) of participants who said they had completed the survey offering free testing visited our clinic: of those who attended, 6% had already been diagnosed as having HIV, while 5% tested positive for HIV. In addition, 8% tested positive for syphilis. CONCLUSIONS: The internet can be used as a tool to access MSM in Peru. The compensation of a free HIV/syphilis test increased the frequency of participation in our online survey, indicating that such incentives may be an effective means of reaching this population. However, as only a small percentage of participants actually reported for testing, future research should develop and assess tailored internet interventions to increase HIV/STI testing and delivery of other prevention services to Peruvian MSM.

Lactoferrin concentration in breast milk of mothers of low-birth-weight newborns.

OBJECTIVES: Lactoferrin (LF) is a breast milk glycoprotein with protective effects against neonatal infections, mainly in premature and low-birth-weight (LBW) neonates. The aims of this study were to determine LF concentration in breast milk of mothers of LBW infants during the first 2 months postpartum, and to identify the factors associated with LF concentration. STUDY DESIGN: Prospective study conducted as a part of an ongoing clinical trial in three Neonatal Units in Peru. We included 346 mothers of neonates with a birth weight <2000 g. We measured LF concentration in four stages of lactation using a commercial enzyme-linked immunosorbent assay kit. Multivariate analysis was performed to assess the association between maternal and neonatal factors, and LF concentration. RESULTS: We collected 695 milk samples. LF mean concentration±standard deviation was 14.92±7.96 mg ml-1 in colostrum (n=277), 10.73±5.67 in transitional milk (n=55), 10.34±6.27 at 1 month (n=259) and 8.52±6.47 at 2 months (n=104). There was a significant difference in LF concentration between different stages of lactation (P<0.001). Mothers with higher LF concentration in colostrum had higher values in the following 2 months. High maternal income and multiple gestation were significantly associated with higher LF levels; in contrast, maternal peripartum infections and male neonatal gender were associated with lower LF levels. CONCLUSIONS: LF concentration in breast milk of mothers of LBW infants was high and remained elevated even at 1 and 2 months postpartum. LF concentration in colostrum was higher in mothers with higher income and multiple pregnancies, and lower in mothers with peripartum infections.

[Neuromyelitis optica spectrum disorders: profile of a cohort according to the 2015 diagnostic criteria]. / Espectro de neuromielitis optica: descripcion de una cohorte segun los criterios diagnosticos de 2015.

INTRODUCTION: The new 2015 criteria for neuromyelitis optica spectrum disorders (NMOSD) have been recently incorporated in the study of different international cohorts. AIM: To describe clinical-radiological characteristics and prognostic factors in patients with NMOSD according to the 2015 criteria. PATIENTS AND METHODS: Retrospective analysis of 36 patients diagnosed with NMOSD according to serologic AQP4 status (positive, negative, unknown and negative + unknown). Clinical and radiological characteristics were compared and possible disability prognostic factors were evaluated. RESULTS: AQP4 were positive in 7 patients, negative in 12 and unknown in 17. Age of presentation was 36.6 ± 16 years, with higher female proportion (4:1). Mean disease duration was 7.4 ± 7.6 years. Most frequent presenting symptoms were acute myelitis (61%), optic neuritis (33%) and area postrema syndrome (11%). Most frequent MRI lesion was longitudinally extensive transverse myelitis (75%). All patients received acute treatment during attacks, and preventive treatment was used in 81% (azathioprine and rituximab mostly prescribed). Median EDSS was 2.0 at the end of follow-up. No differences were observed in any of the variables comparing serologic status. Age of first attack was prognostic, with direct correlation with EDSS. First attack in < 30 years was protective, meanwhile > 50 years old patients had increased risk of disability. CONCLUSIONS: The 2015 criteria allow the description and classification of NMOSD patients within different cohorts. Age of first attack seems to be a prognostic factor for developing disability.

TITLE: Espectro de neuromielitis optica: descripcion de una cohorte segun los criterios diagnosticos de 2015.Introduccion. Los nuevos criterios diagnosticos de 2015 del espectro de neuromielitis optica (NMO) estan comenzando a utilizarse en diferentes poblaciones en el mundo. Objetivo. Describir las caracteristicas clinicorradiologicas y pronosticas de pacientes diagnosticados de NMO con los criterios de 2015. Pacientes y metodos. Analizamos retrospectivamente 36 pacientes diagnosticados de NMO con los actuales criterios. Se generaron cuatro grupos segun la serologia de antiacuaporina 4 (positivos, negativos, desconocidos y negativos mas desconocidos agrupados). Se compararon sus caracteristicas clinicorradiologicas y se evaluaron posibles variables pronosticas de discapacidad. Resultados. Encontramos siete pacientes seropositivos, 12 negativos y 17 desconocidos. La edad de inicio fue de 36 ± 16 años, con mayor proporcion de mujeres (4 a 1). La duracion de la enfermedad fue de 7,4 ± 7,6 años. Los sintomas iniciales mas frecuentes fueron mielitis (61%), neuritis optica (33%) y sindrome del area postrema (11%). La lesion mas frecuente en la resonancia magnetica fue la mielitis longitudinalmente extensa (75%). Todos los pacientes recibieron tratamiento agudo, y el preventivo se utilizo en el 81%; la azatioprina y el rituximab fueron los que mas se usaron. La mediana de la Expanded Disability Status Scale (EDSS) fue de 2 al final del seguimiento. No hubo diferencias significativas en las variables clinicorradiologicas entre los distintos grupos de pacientes. La edad de inicio fue pronostica y presenta correlacion directa con la EDSS. El inicio antes de los 30 años fue protector y, despues de los 50 años, un factor de riesgo para mayor discapacidad. Conclusiones. Los actuales criterios permiten describir diferentes cohortes. La edad de inicio parece ser un factor pronostico para desarrollar discapacidad.

Emerging genetic diversity of HIV-1 in South America.

OBJECTIVE: Genotype determination and risk group analysis of HIV-1 infected individuals in selected regions of South America. DESIGN: Cross-sectional convenience sampling of HIV-1-positive individuals in Peru, Ecuador, Uruguay and Paraguay from March, 1994 through September, 1998. METHODS: HIV-1-positive subjects were identified through the national AIDS surveillance program in each country. A standardized questionnaire was used to obtain demographic, clinical and risk factor data on each study subject. Viral DNA was extracted from participants' peripheral blood mononuclear cells either directly or after co-cultivation. A nested PCR was used to obtain selected fragments of the envelope genes for genotyping by the heteroduplex mobility assay (HMA). A 600 bp sequence encompassing the V3 loop was sequenced from a selection of 23 of these samples for phylogenetic analysis and confirmation of HMA genotype. RESULTS: Among the 257 successfully genotyped HIV-1-positive samples, genotype B was found in 98.3% (228/232) of those obtained from subjects in Peru, Ecuador, and Paraguay. In contrast, 56% (14/25) of the samples from Uruguay were genotype F, and the remainder were genotype B. Genotype F was detected for the first time in Peru (2/224) and Paraguay (1/4), and genotype A for the first time in Peru (1/224). Phylogenetic analysis confirmed the genotype identified by HMA in the 23 samples sequenced. There was no detectable genetic clustering of HIV-1 within the different high-risk groups or geographic locations. CONCLUSIONS: These findings verify and extend the presence of several different HIV-1 genotypes in South America.

Lipid-mediated enhancement of transfection by a nonviral integrin-targeting vector.

Nonviral vectors consisting of integrin-targeting peptide/DNA (ID) complexes have the potential for widespread application in gene therapy. The transfection efficiency of this vector, however, has been limited by endosomal degradation. We now report that lipofectin (L) incorporated into the ID complexes enhances integrin-mediated transfection, increasing luciferase expression by more than 100-fold. The transfection efficiency of Lipofectin/Integrin-binding peptide/DNA (LID) complexes, assessed by beta-galactosidase reporter gene expression and X-gal staining, was improved from 1% to 10% to over 50% for three different cell lines, and from 0% to approximately 25% in corneal endothelium in vitro. Transfection complexes have been optimized with respect to their transfection efficiency and we have investigated their structure, function, and mode of transfection. Both ID and LID complexes formed particles, unlike the fibrous network formed by lipofectin/DNA complexes (LD). Integrin-mediated transfection by LID complexes was demonstrated by the substantially lower transfection efficiency of LKD complexes in which the integrin-biding peptide was substituted for K16 (K). Furthermore, the transfection efficiency of complexes was shown to be dependent on the amount of integrin-targeting ligand in the complex. Finally, a 34% reduction in integrin-mediated transfection efficiency by LID complexes was achieved with a competing monoclonal antibody. The role of lipofectin in LID complexes appears, therefore, to be that of a co-factor, enhancing the efficiency of integrin-mediated transfection. The mechanism of enhancement is likely to involve a reduction in the extent of endosomal degradation of DNA.

Lipoadenofection-mediated gene delivery to the corneal endothelium: prospects for modulating graft rejection.

BACKGROUND: Gene transfer to the corneal endothelium has potential for the prevention or reversal of corneal allograft rejection. Previous work has examined adenoviral vectors for gene transfer to endothelium. These have a number of theoretical and practical disadvantages, both for experimental and clinical applications. We have therefore used lipoadenofection, in which plasmid DNA is delivered using a combination of liposomes and adenovirus, to transfer marker genes to the cornea. METHODS: Corneas were obtained from New Zealand White rabbits and cultured ex vivo using standard conditions. The corneas were transfected using either lipofection or lipoadenofection with plasmids encoding marker genes. The efficiency of gene transfer and the location and kinetics of gene expression were determined. We also investigated the delivery of a gene construct containing an inducible promoter that is activated by tumor necrosis factor (TNF), to determine whether expression of the relevant genes could be controlled by exogenous factors such as cytokines. RESULTS: This study shows that gene expression is limited to the endothelium and that expression is transient. Furthermore, we have shown that expression of a gene controlled by an inducible promoter only occurs when TNF is present. CONCLUSIONS: These data indicate that lipofection is an efficient method to transfer therapeutic genes to the corneal epithelium, and that it can be used to transfer constructs that utilize an inducible promoter controlled by TNF. As TNF is present in the aqueous humor during allograft rejection, and this is in contact with the corneal endothelium, this has the potential to restrict expression of a therapeutic gene to rejection episodes in the cornea.

Transient increase of brain derived neurotrophic factor mRNA expression in substantia nigra reticulata after partial lesion of the nigrostriatal dopaminergic pathway.

By using non-isostopic in situ hybridization we have demonstrated a transient increase of BDNF mRNA in the lateral subregion of the substantia nigra pars reticulata 1 week after intrastriatal application of 6-OH-DA. These changes correlate with a partial reduction of dopamine (DA) content in the striatum but with a normal tyrosine hydroxylase immunoreactivity in substantia nigra pars compacta. Our data suggest that non-DA, BDNF expressing cells in substantia nigra pars reticulata may play a role in neuronal protection after partial lesions of the DA nigrostriatal pathway.

Lactate dehydrogenase isoenzymes in patients with essential thrombocythemia.

Various abnormalities have been described in platelets of patients with Essential Thrombocythemia (ET), including alteration in the glycolytic pathway and increased lactate production. Lactate dehydrogenase (LDH) isoenzymes were studied in 15 of these patients. Relative activity of LDH-5 isoenzyme was higher comparing with normal platelets (p < 0.05), while LDH-3 activity was diminished (p < 0.05). LDH-1, LDH-2 and LDH-4 isoenzymes were unchanged. We also found an altered profile of LDH isoenzymes in serum. These findings can contribute to improve the knowledge of platelet defects in ET and be useful in the diagnosis of these patients.

Arachidonic acid metabolism in platelets of patients with essential thrombocythaemia.

Platelet aggregation tests and studies comprising [14C] arachidonic acid [14C]AA incorporation, release and metabolism were performed in resting and thrombinstimulated platelets of 11 patients with essential thrombocythaemia (ET) and 11 normal subjects. Nine patients had abnormal aggregation tests. Incorporation and distribution of [14C]AA in main platelet phospholipids (PLs) was similar in both groups. Activated platelets of patients with ET released more radioactivity from PLs that controls (13.7 +/- 5.4% versus 8.2 +/- 1.9%, p < 0.01). The formation of 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) was also increased (3.3 +/- 1.4% of total radioactivity versus 1.6 +/- 0.4% in controls (p < 0.0001). The same results were obtained for the generation of thromboxane B2 (p < 0.01). We did not detect differences in the formation of 12-L-hydroxy- 5,8,10,14-eicosatetraenoic acid (3.3 +/- 1.7% in patents versus 2.0 +/- 0.5% in controls). These results indicate that platelets of patients with ET have an increased activity of phospholipases and suggest a facilitated metabolism of arachidonate by the prostaglandinsynthetase pathway. Our results also demonstrate that impairment of aggregation tests in these patients was not due to a defective activity of the enzymes involved in the release and metabolism of AA by platelets.

Long-term continuous ambulatory peritoneal dialysis reduces the expression of CD11b, CD14, CD16, and CD64 on peritoneal macrophages.

OBJECTIVE: To characterize phenotypically the macrophages from nocturnal peritoneal effluent (NPE) in patients on continuous ambulatory peritoneal dialysis (CAPD), and to determine the influence of the length of this therapy on macrophage (M phi) function. DESIGN: Cross-sectional descriptive study. PATIENTS: Fifty-five patients on CAPD who were classified into short-, medium-, and long-term groups according to their time on CAPD. Peritoneal macrophages (PM phi) were also characterized in 7 patients at the time of catheter placement, and there were 13 normal controls. INTERVENTIONS: Macrophages were collected from NPE by centrifugation. MEASUREMENTS: Membrane receptor expression was evaluated by flow cytometry analysis. RESULTS: Flow cytometry analysis revealed that the expression of CD11b, CD16, CD64, and CD14 on NPE macrophages was reduced during the course of CAPD treatment, reaching levels which represented a 40%-50% reduction of the cell surface expression detected at the start of the treatment or on normal control macrophages. Both normal and CAPD PM phi expressed CD4, CD69, and CD71 very weakly and lacked CD25. No changes in HLA-DR or in other adhesion protein (CD11a, CD11c, CD18, CD54) expression were detected, and levels were similar in both patients and normal controls. CONCLUSION: Our results show that long-term CAPD might affect Fc gamma receptor-mediated phagocytosis by reducing the expression of CD16, CD64, and CD11b. Lower CD11b and CD14 expression would also impair PM phi adhesion to mesothelial structures.

Transformed mesothelial cells in patients on CAPD for medium- to long-term periods.

OBJECTIVE: To describe the characteristics of abnormal cells present in the peritoneal effluent of 4 continuous ambulatory peritoneal dialysis (CAPD) patients; the cells were accidentally detected in a longitudinal study of cell populations in 83 patients. DESIGN: Descriptive study. PARTICIPANTS: Four stable CAPD patients (2 male, 2 female). INTERVENTIONS: Peritoneal cells were collected from nocturnal peritoneal effluent (NPE) by centrifugation. MEASUREMENTS: Light microscopy, ultrastructural, cytochemical, and immunohistochemical characteristics were studied. RESULTS: The abnormal cells were characterized by a flat appearance, large size (diameter 100 microns)--six to ten times larger than a normal macrophage, a broad acidophilic cytoplasm with rare granulations, and a low nucleus/cytoplasm ratio. The nucleus was pyknotic, with dense chromatin and sometimes appeared fragmented. Its number presented a considerable variability between the patients and was much higher in the 2 females. This number remained stable in each patient over time. These cells were negative for beta-glucuronidase and positive for PAS stain with variable intensity. A very low number of flat cells were positive for vimentin with weak intensity, whereas cytokeratin and epithelial membrane antigen (EMA) were positive in a higher number of cells with medium to strong intensity. Ultrastructural studies showed numerous short surface microvilli, cytoplasm well-developed with intracytoplasmic lumina and abundant, dispersed intermediate filaments, scattered mitochondria, and stacks of rough endoplasmic reticulum were observed. Dispersed secretory vacuoles and isolated lipid vacuoles were present. CONCLUSION: All these features imply that they are mesothelial in origin and are suggestive of a change known as peritoneal squamous metaplasia. To date, the clinical follow-up of our patients has shown a benign outcome; further studies are necessary to elucidate the significance of this peritoneal squamous metaplasia in CAPD patients.

[Variable response to the biological inhibition of platelets by abciximab in patients subjected to percutaneous coronary angioplasty]. / Respuesta variable a la inhibición biológica de las plaquetas por abciximab en pacientes sometidos a revascularización coronaria percutánea.

INTRODUCTION AND OBJECTIVES: Abciximab has been shown to reduce the risk of thrombotic complications during coronary angioplasty, however there are still many aspects to be resolved. The aim of this study was to investigate the various biological effects of abciximab on platelets during coronary angioplasty. METHODS: The degree of platelet inhibition (with 5 and 20 mol/l concentrations of ADP), occlusion time (measurement of platelet haemostatic capacity, PFA-100), and the platelet activation markers were determined in 15 patients who underwent basal coronary angioplasty and abciximab treatment. Determinations were obtained before, 15 minutes after procedure initiation, at procedure termination, and 24 hours after procedure termination. RESULTS: More than 80% platelet aggregation inhibition was observed in 13 patients during the procedure, but after 24 hours (p < 0.05) was only detected in two. The occlusion time during the procedure was > 300 sec. in 13 patients, 6 of whom evolved to normal values after 24 hours (p < 0.05). A high correlation (p = 0.02) was found between these two parameters during the intervention, but not after 24 hours. No platelet inhibition or occlusion time changes were observed in 2 patients during the study. The expression of p-selectin increased significantly during the procedure (p < 0.05). CONCLUSIONS: The variability of platelet function inhibition and existence of circulating activation during coronary angioplasty following the administration of abciximab support the use of early analytical controls with the objective of modifying guidelines for use in order to optimize its effect or to combine it with other antithrombotic agents.

Knee lymphocutaneous fistula secondary to knee arthroplasty.

Lower limb lymphorrhea secondary to a surgical procedure is a rare but difficult-to-solve complication. In lower limb, this entity is frequently associated with vascular procedures around the inguinal area. We report on a case of a knee lymphocutaneous fistula secondary to a knee revision arthroplasty. To our knowledge, no previous reports regarding this complication have been published.