Animal trypanosomosis: making quality control of trypanocidal drugs possible.

African animal trypanosomosis is arguably the most important animal disease impairing livestock agricultural development in sub-Saharan Africa. In addition to vector control, the use oftrypanocidal drugs is important in controlling the impact of the disease on animal health and production in most sub-Saharan countries. However, there are no internationally agreed standards (pharmacopoeia-type monographs or documented product specifications) for the quality control of these compounds. This means that it is impossible to establish independent quality control and quality assurance standards for these agents. An international alliance between the Food and Agriculture Organization of the United Nations, the International Federation for Animal Health, the Global Alliance for Livestock Veterinary Medicines, the University of Strathclyde and the International Atomic Energy Agency (with critical support from the World Organisation for Animal Health) was established to develop quality control and quality assurance standards for trypanocidal drugs, with the aim of transferring these methodologies to two control laboratories in sub-Saharan Africa that will serve as reference institutions for their respective regions. The work of the international alliance will allow development of control measures against sub-standard or counterfeit trypanocidal drugs for treatment of trypanosome infection. Monographs on diminazene aceturate (synonym: diminazene diaceturate), isometamidium chloride hydrochloride, homidium chloride and bromide salts and their relevant veterinary formulations for these agents are given in the annex to this paper. However, the authors do not recommend use of homidium bromide and chloride, because of their proven mutagenic properties in some animal test models and their suspected carcinogenic properties.

Enhanced phosphorus removal from sewage in mesocosm-scale constructed wetland using zeolite as medium and artificial aeration.

Phosphorus (P) contained in sewage maybe removed by mesocosm-scale constructed wetlands (MCW), although removal efficiency is only between 20% and 60%. P removal can be enhanced by increasing wetland adsorption capacity using special media, like natural zeolite, operating under aerobic conditions (oxidation-reduction potential (ORP) above +300 mV). The objective of this study was to evaluate P removal in sewage treated by MCW with artificial aeration and natural zeolite as support medium for the plants. The study compared two parallel lines of MCW: gravel and zeolite. Each line consisted in two MCW in series, where the first MCW of each line has artificial aeration. Additionally, four aeration strategies were evaluated. During the operation, the following parameters were measured in each MCW: pH, temperature, dissolved oxygen and ORP. Phosphate (PO4(-3) - P) and chemical oxygen demand (COD), five-day biological oxygen demand (BOD5), total suspended solids (TSS) and ammonium. (NH4(+) - N) were evaluated in influents and effluents. Plant growth (biomass) and proximate analysis for P content into Schoenoplectus californicus were also performed. The results showed that PO4(-3) - P removal efficiency was 70% in the zeolite medium, presenting significant differences (p < .05) with the results obtained by the gravel medium. Additionally, aeration was found to have a significant effect (p < .05) only in the gravel medium with an increase in up to 30% for PO43 - P removal. Thus, S. californicus contributed to 10-20% of P removal efficiency.

Effects of aeration and natural zeolite on ammonium removal during the treatment of sewage by mesocosm-scale constructed wetlands.

The objective was to evaluate the effects of intermittent artificial aeration cycles and natural zeolite as a support medium, in addition to the contribution of plants (Schoenoplectus californicus) on NH4(+)-N removal during sewage treatment by Constructed Wetlands (CW). Two lines of Mesocosm Constructed Wetland (MCW) were installed: (a) gravel line (i.e. G-Line) and (b) zeolite line (i.e. Z-Line). Aeration increased the NH4(+)-N removal efficiency by 20-45% in the G-Line. Natural zeolite increased the NH4(+)-N removal efficiency by up to 60% in the Z-Line. Plants contributed 15-30% of the NH4(+)-N removal efficiency and no difference between the G-Line and the Z-Line. Conversely, the NH4(+)-N removal rate was shown to only increase with the use of natural zeolite. However, the MCW with natural zeolite, the NH4(+)-N removal rate showed a direct relationship only with the NH4(+)-N influent concentration. Additionally, relationship between the oxygen, energy and area regarding the NH4(+)-N removal efficiency was established for 2.5-12.5 gO2/(kWh-m(2)) in the G-Line and 0.1-2.6 gO2/(kWh-m(2)) in the Z-Line. Finally, it was established that a combination of natural zeolite as a support medium and the aeration strategy in a single CW could regenerate the zeolite's adsorption sites and maintain a given NH4(+)-N removal efficiency over time.

Asociación del nivel socioeconómico y educacional en los egresos por cáncer de mama en Chile durante los años 2001 al 2016 / Association of the socioeconomic and educational level in the breast cancer hospital outbreaks in Chile during the years 2001 to 2016

Introducción: El cáncer de mama constituye la primera causa de muerte en los cánceres en Chile según Globocan 2018. Dentro de los factores que explican esta alta mortalidad encontramos una baja tasa de detección y de realización de mamografías en los niveles socioeconómicos altos. Es por esto que comprender las causas de defunción y los factores que afectan en la mortalidad y letalidad por cáncer de mama en los últimos 17 años nos permitirá enfocar las políticas públicas de los próximos 50 años. Los objetivos generales de este trabajo fueron caracterizar los egresos hospitalarios en los pacientes por cáncer de mama según la edad, el sexo, la previsión, el nivel socioeconómico y educacional en Chile durante los años 2001 al 2016 y calcular la mortalidad y letalidad específica en estas mismas variables durante los años 2001 a 2016. El objetivo específico es asociar las variables socioeconómicas y educacionales, estimando los Odd's ratios de las variables en los egresos hospitalarios por cáncer de mama en Chile durante los años 2001 al 2016. Materiales y Métodos: Estudio de cohorte longitudinal retrospectivo en 81,072 egresos hospitalarios y 20,220 defunciones obtenidas de la página DEIS MINSAL, años 2001-2016. Para el análisis univariado se efectuó una regresión de ajuste de tasas Prais-weinstein según edad y sexo según modelo OMS de ajuste de tasas. Para las variables de tipo discreta se describieron mediante porcentajes y tasas y para las variables de tipo continua se utilizó mediana y desviación estándar. Se efectuó un test de smirnov-kolmolgorov para determinar el tipo de distribución y de normalidad de las muestras. Para las variables de tipo dicotómica se utilizó un modelo de regresión logística binaria para describir estas variables y determinar la posible asociación entre el nivel socioeconómico y educacional de las pacientes diagnosticadas por cáncer de mama. Resultados: Murieron 1,88 veces más personas de nivel socioeconómico alto con un IC entre 1,83- 1,94 con respecto a la población de nivel socioeconómico bajo. En cambio, las personas con un mayor nivel educacional murieron 0,5 veces menos según la regresión realizada respecto al bajo nivel educacional con un IC entre 0,47- 0,52, pero a menor nivel educacional aumentó 20 veces la mortalidad, constituyendo una causa inversa. Respecto al sexo las mujeres murieron 2,08 veces más que los hombres. Para el nivel socioeconómico alto en relación al bajo un OR [1.88 (1.83 a 1,94)], p<0,0001], para el nivel educacional alto en relación al bajo fue a favor del mayor nivel educacional con OR [0,5 (0,47 - 0,52)] y en cuanto a la comparación de sexos un OR [1,04 (1,03-2,17), p=0,039]. Es decir, la diferencia entre mortalidad que hubo fue significativa para todos los intervalos tanto para sexo, nivel educacional como para nivel socioeconómico. Se encontró una constante de 0,013 de mortalidad basal, es decir, todos tienen 1,3% de riesgo de morir por cáncer de mama independiente del nivel socioeconómico, educacional y del sexo. Conclusión: Existen diferencias estadísticamente significativas respecto a la mortalidad entre los niveles socioeconómicos altos y bajos y también en nivel educacional, sin embargo, al realizar los métodos de regresión se obtuvo una mayor mortalidad y mayor riesgo de morir por cáncer de mama en los niveles socioeconómicos más altos asociados a, probablemente, la menor cantidad de tamizajes y realización de mamografías en este estrato. A partir del año 2008 se observó un incremento a los niveles originales observados al inicio del segundo milenio incrementando las diferencias existentes en los índices de desigualdad tanto por nivel educacional como por nivel socioeconómico incrementando en 20 veces respecto al nivel educacional, y 1.88 respecto al nivel socioeconómico.

Introduction: Breast cancer is the leading cause of death in cancers in Chile according to Globocan 2018. Among the factors that explain this high mortality, we find a low rate of detection and performance of mammograms in high socioeconomic levels. This is why understanding the causes of death and the factors that affect mortality and fatality from breast cancer in the last 17 years will allow us to focus on public policies for the next 50 years Materials and Methods: Retrospective longitudinal cohort study in 79,996 hospital discharges and 20,220 deaths obtained from the DEIS MINSAL page, years 2001 -2016. For the univariate analysis, a Prais-Weinstein rate adjustment regression was performed according to age and sex according to the WHO rate adjustment model. For discrete type variables, they were described by percentages and rates, and median and standard deviation were used for continuous type variables. A smirnov-kolmolgorov test was performed to determine the type of distribution and normality of the samples. For dichotomous variables, a binary logistic regression model was used to describe these variables and determine the possible association between the socioeconomic and educational level of the patients diagnosed with breast cancer. Abstract: In this observational, longitudinal and retrospective study with 101.292 patients that includes men and women of all ages with diagnosis of breast cancer all along Chile, we´ll analyze the impact of socioeconomic level, evaluated through educational level and money income, into the prevalence, mortality and lethality of breast cancer in the years 2001 to 2016. Results: People with a high socioeconomic level died 1.88 times more, with a CI between 1.83 and 1.94, than those with a low socioeconomic level. On the other hand, people with a higher educational level died 0.5 times less according to the regression carried out with respect to the low educational level with a CI between 0.47 and 0.52, but the lower the educational level the mortality increased 20 times, constituting an inverse cause. Regarding sex, women died 2.08 times more than men. For the high socioeconomic level in relation to the low one an OR [1.88 (1.83 to 1.94)], p<0.0001], for the high educational level in relation to the low one it was in favor of the higher educational level with OR [0.5 (0.47 - 0.52)] and as for the comparison of sexes an OR [1.04 (1.03-2.17), p=0.039]. In other words, the difference between mortality was significant for all the intervals for sex, educational level and socioeconomic level. A constant baseline mortality of 0.013 was found, i.e., everyone has a 1.3% risk of dying from breast cancer regardless of socioeconomic level, educational level and sex. Conclusions: There are statistically significant differences in mortality between high and low socioeconomic levels and also in educational level; however, when regression methods were used, a higher mortality and higher risk of dying from breast cancer was obtained in the higher socioeconomic levels, probably associated with the lower number of screenings and mammograms performed in this stratum. As of 2008, an increase to the original levels observed at the beginning of the second millennium was observed, increasing the existing differences in the inequality indexes both by educational level and socioeconomic level, increasing by 20 times with respect to educational level, and 1.88 times with respect to socioeconomic level.

Simultaneous adult T-cell leukemia/lymphoma and sub-acute polyneuropathy in a patient from Chile.

This paper reports a case of adult T-cell leukemia/lymphoma associated with human T-cell lymphotropic virus type I (HTLV-I) diagnosed in a Chilean patient who developed after 1 1/2 years a crisis with a progressive sensorimotor polyneuropathy. Serum and cerebrospinal fluid HTLV-I antibody tests were positive and HTLV-I DNA was clonally integrated in peripheral lymphocytes. This case is unusual in having simultaneous neurological disease. Along with other recent data from South America, this suggests that the endemic area of HTLV-I may spread far beyond the Caribbean area.

Clinical and neuropathological study of six patients with spastic paraparesis associated with HTLV-I: an axomyelinic degeneration of the central nervous system.

Between 1990 to 1994, 6 TSP/HAM patients, 3 women and 3 men with an average age of 57.1 years (39 to 76 years old), who died in the Salvador Hospital were submitted to postmortem examination. The mean time of paraparesis was 7 years (3 to 17 years), and 2 patients had pseudobulbar signs. Three cases had macroscopic atrophy of the spinal cord. Histologically, all cases had lesions in the pyramidal tracts and 4 cases showed somatotopic lesions of the Goll's tracts which followed a "dying back" ascendant and descendant distribution, respectively. In 2 cases, both of which had intellectual impairment, demyelination of the subcortical and parathalamic areas was observed without U fiber involvement. Abnormal vessels with gross thickening of the adventitia, many of them with lymphocytic cuffs, were seen everywhere, especially in the spinal cord, brain stem, midbrain and meninges, but no relation between these findings and the parenchymal lesions was observed. Also, in the cases with posterior column involvement, neuronal changes and proliferation of satellite cells in the dorsal ganglia were found. All cases showed histological sialoadenitis and none had inflammatory muscle changes. We conclude that the lesions affected the neuraxis in a systemic axial fashion as in degenerative diseases, and did not seem to be secondary to vascular or inflammatory abnormalities.

HTLV-I positive progressive spastic paraparesis (TSP) associated with a lymphoid disorder in three Chilean patients.

We describe the clinical and laboratory features in three Caucasian Chilean patients with tropical spastic paraparesis (TSP) associated with/or preceded by a lymphoproliferative disorder involving cutaneous lesions and localised lymphadenopathy. The neurological symptoms and signs were characteristic of TSP and CSF examination revealed the presence of oligoclonal bands. All three patients had a moderate leucocytosis (10-14 x 10(9)/l) with eosinophilia and a minority (2-4%) of circulating atypical polylobed or ATLL-like lymphocytes. Lymph node histology showed a diffuse pattern of infiltration (1 case) and marked expansion of the paracortical zone with convoluted lymphocytes and immunoblasts (2 cases). Skin biopsy demonstrated a dermal lymphoid infiltration with epidermotropism. Antibodies to HTLV-I were detected in the serum and CSF in the three patients and Southern blot analysis of peripheral blood mononuclear cells showed a monoclonal integration of HTLV-I proviral DNA in one case whereas in the two others the pattern was indicative of low level polyclonal integration. All three patients were treated with prednisolone and one with PUVA with transient partial response on the skin and neurological manifestations. Two patients died months to 5 years from presentation and the other is alive 12 years from diagnosis with active neurological and skin disease. The simultaneous occurrence of HTLV-I associated TSP with smouldering ATLL and a cutaneous ATLL or pre-leukaemic form is discussed.

Tropical spastic paraparesis.

Human T-cell lymphotropic virus type I (HTLV-I) is the cause of endemic tropical spastic paraparesis (TSP) or HTLV-I-associated myelopathy (HAM). Because TSP/HAM is not a fatal disease, the neuropathology of this disease, albeit relatively well understood, is based on the examination of just a few incidental cases. We summarise our experience with the neuropathology of tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM). We studied three cases of TSP/HAM from different parts of the world. We demonstrated peculiar lamellated structures, called "multilamellar bodies" (MLB). It is tempting to suggest that MLB may represent specific ultrastructural markers of TSP/HAM. The pathology of the anteriorand posterior horns was similar and comprised axonal degeneration, accompanied by extensive astrocytic gliosis. Lymphocytic infiltration, particularly observed as "cuffs" around blood vessels, was scattered among other cellular elements. Ultrastructurally, myelin sheaths were relatively well preserved, and some demyelinated but not remyelinated fibres were observed. Moreover, axons with abnormal accumulations of neurofilaments, suggestive of axonal degeneration, were detected. Several axons contained Hirano bodies. In many samples glial processes replaced most of the remaining neuropil.

Development of a high pressure liquid chromatography method for the determination of mycophenolic acid and its glucuronide metabolite in small volumes of plasma from paediatric patients.

In order to facilitate the simultaneous determination of the levels of mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG) in plasma samples a step wise gradient high performance liquid chromatography (HPLC) method was developed using UV detection system and naproxen as an internal standard. The analytes were extracted from plasma using Strata-X polymeric solid phase extraction (SPE) cartridges. Separation was achieved within a total chromatographic run time of 18 min at 1.0 ml/min flow rate using a Hv PURITY C18 column. The method was found to be linear over the concentration range investigated, 1.0-16 microg/ml (r > 0.99) for MPA and 10-160 microg/ml (r > 0.99) for MPAG. The limit of detection was 0.1 microg/ml for both MPAG and MPA. The intra- and inter-day imprecisions expressed as R.S.D. were 7.8 and 6.6%, respectively, for MPA (1 microg/ml) and 6.2% and 5.6%, respectively, for MPAG (20 microg/ml). The average extraction recovery from plasma was 93.06%, for MPA and 92.41% for MPAG. The method developed was found to be accurate and precise in quantifying the level of MPA and MPAG over a their therapeutic range of concentrations in small volumes of plasma and thus can be effectively used in the routine drug monitoring procedures and pharmacokinetic studies. It was also developed in such a way that it should be easily coupled to an electro-spray ionization mass spectrometer should greater sensitivity be required.

Somatosensory evoked potentials and dopaminergic responsiveness to apomorphine and levodopa in parkinsonian patients.

Short-latency somatosensory evoked potentials (SSEPs) were recorded from 10 parkinsonian patients in 'off' and 'on' states induced by apomorphine and levodopa. The effects of apomorphine and long-term levodopa treatment on the frontal N30 component were assessed and compared with healthy controls. Nine of 10 patients tested with apomorphine showed a significant improvement (p<0.01) in N30 frontal component amplitude whereas in six of eight patients similarly assessed with levodopa we obtained a comparable improvement in SSEPs (p<0.01). Parietal SSEPs remained unchanged. This normalization of frontal SSEPs was concomitant with the clinical response and in some patients preceded the motor response. No changes were obtained in control subjects. The improvement in N30 potential occurred regardless of disease duration or the presence of motor fluctuations. SSEPs may represent an objective approach for assessing the dopaminergic response and the fluctuations of motor disability in parkinsonian patients.

Progressive spastic paraparesis associated with human T-cell leukemia virus type I (HTLV-I).

Patients with progressive spastic paraparesis (PSP), commonly middle-aged women, are distributed throughout the country of Chile. During the three years from 1987 to 1990, we collected 83 cases of PSP from among 225 patients with various neurological diseases. The clinical picture was of a bilateral pyramidal syndrome, with sensory deficits in only 15.5% of the cases, and a slow illness progression in the majority of them. In patients with PSP, antibody to human T-cell leukemia virus type I (HTLV-I) was analyzed by enzyme linked immunosorbent assay (ELISA) and confirmed by western blot analysis. Forty-five (54.2%) patients were anti-HTLV-I antibody positive in cerebrospinal fluid (CSF) and peripheral blood. Among them, 2 patients had leukemia/lymphoma and one had Sjögren syndrome. In the laboratory study of seropositive PSP, mononuclear pleocytosis was found in 35.7%; there was an abnormal increase of the IgG index in 66.6% and an increase in CD2 in blood and CSF, and CD4 in blood. A delayed latency of somatosensory evoked potentials was observed in 90.9%. The neuropsychological study revealed a WAIS with a mean verbal IQ of 80.7 and a mean performance IQ of 84.8. The most impaired items were digit symbol and digit span. Seven subjects (18.9%) with anti-HTLV-I antibody were found among 37 relatives from 19 anti-HTLV-I positive cases of PSP.

Impact of parity on anthropometric measures of obesity controlling by multiple confounders: a cross-sectional study in Chilean women.

AIM: To find out whether there is an association between parity and obesity, evaluated through body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) in Chilean women after controlling for sociodemographic characteristics, health risk and gynaeco-obstetric factors. DESIGN: Cross-sectional study, using baseline data of the San Francisco Project. SETTING: San Francisco de Mostazal, located in the central region of Chile, 6512 Chilean-Hispanic women (Spanish heritage with a variable indigenous component). METHODS: A weighted random sample of 508 women who had their first pregnancy inside the primary child-bearing ages. Data were collected between 1997 and 1999. Statistical associations between parity and different anthropometric measurements of adiposity in multiple linear (MLnR) and logistic regression models (MLtR) were evaluated. RESULTS: In MLnR a modest parity-related increment in BMI and practically null increment in WC, WHR and WHtR was observed. Covariates that showed a statistically significant association with anthropometric measures of adiposity were age, low education, marital status, employment, smoking, smoking cessation, hypertension, diabetes, dyslipidaemia, parent's obesity, menarche and fetal macrosomia. Crude odds ratio (OR) showed a strong association between parity and anthropometric markers of obesity. Nevertheless, after adjustments in MLtR models, the association remained only for BMI. All the measures of abdominal obesity related to parous women showed OR smaller than 1 (95% confidence intervals 0.57 to 0.96). CONCLUSIONS: Parity modestly influences BMI, but does not seem to be related to WC, WHR and WHtR after controlling by confounders. Parity can increase adiposity but not necessarily following an abdominal pattern.

[Intravenous tissue plasminogen activator in the treatment of acute ischemic stroke: feasibility, safety, and efficiency in the 2 first years of the clinical practice]. / Activator del plasminógeno tisular intravenoso en el tratamiento del infarto cerebral agudo: factibilidad, seguridad y eficacia en los primeros dos años de práctica clínica.

BACKGROUND: The only effective therapy for the treatment of acute ischemic stroke is the infusion of tissue plasminogen activator in the first three hours after the onset of symptoms. AIM: To report the experience with tissue plasminogen activator infusion in the treatment of acute ischemic stroke. PATIENTS AND METHODS: Ten males and 10 females, aged 52 to 85 years old with an acute ischemic stroke, admitted within 89 min after the onset of symptoms were studied. Tissue plasminogen activator was infused following the guidelines designed by the National Institute of Neurological Disorders and Stroke (NINDS). Patients were assessed according to Rankin scale after three months of follow up. RESULTS: All patients had normal CAT scans. The delay between the onset of symptoms and the infusion ranged from 75 to 180 min. One patient had a gastrointestinal bleeding due to a gastric ulcer and one patient had a fatal intracranial hemorrhage. After three months of follow up, 38% of patients had a good recuperation (Rankin 0 to 1), 33% had a mild to moderate disability (Rankin 2 or 3) and 14% had a moderate to severe disability (Rankin 4). There was a 15% mortality. CONCLUSIONS: This series show that treatment of acute ischemic stroke with tissue plasminogen activator is feasible and safe. The obtained results are similar to those reported abroad.

[Transient ischemic attacks in Chilean patients and their relationship with the country's pattern of cerebrovascular disease]. / Crisis isquémicas transitorias en chile y su relación con el patrón de enfermedad cerebrovascular chileno.

BACKGROUND: It has been postulated that in Chile, transient ischemic attacks (TIA) are much less frequent than in Caucasian populations. A lesser frequency of these attacks would be due to a higher frequency of intracranial atheromas, whereas an abundance of TIA would be a result of a higher prevalence of extracranial atheromas. AIM: To study the history of TIA in a group of Chilean patients with an acute episode of cerebrovascular disease. PATIENTS AND METHODS: One hundred forty nine patients admitted to a Neurology service of a public hospital in Santiago, with an acute stroke, were studied. Patients and close relatives were interrogated about previous symptoms of TIA using a structured questionnaire. RESULTS: One hundred nine patients had an ischemic and 40 patients a hemorrhagic stroke. Twenty patients with ischemic stroke had a history of TIA (18%). Fifteen out of 74 patients without a cardiac source of emboli (20%) and five out of 35 cases with an embolic source (14%) had a TIA preceding their stroke. Three out of 40 patients (8%) with hemorrhagic stroke had a history of TIA. CONCLUSIONS: This study does not support nor reject the hypothesis of a Chilean pattern of cerebrovascular disease unlike that found in Northern Caucasians.

[HTLV-I clinical pathological spectrum]. / HTLV-I espectro clinico patologico.

HTLV-I has been revealed as the etiological factor of the Tropical Spastic Paraparesis (TSP) and of the T-cell leukemia-lymphoma of the adult (ATLL). Recently, it has also been associated to some forms of polymyositis, polyarthritis, polyneuropathies, Sjögren's syndrome, thrombocytopenia and lympho-alveolitis. The clinical and pathological spectrum of this retrovirus is analyzed taking into account the Chilean cases and those reported by the international medical literature.