Estrategia Integral para la Ampliación del Rol de Enfermería en la Atención Primaria de Salud / Primary Healthcare Nursing Role Enhancement Integral Strategy / Estratégia Integral para a Ampliação do Papel de Enfermagem na Atenção Primária de Saúde

RESUMEN Introducción: Los desequilibrios entre la carga de enfermedades crónicas y la insuficiente respuesta del sistema de salud, agudizan las desigualdades en cobertura así como el acceso efectivo a los servicios. La Secretaría de Salud, integró grupos de trabajo para diseñar una estrategia que contribuya a la solución de esta problemática a través de la optimización y distribución de las funciones de enfermería. Objetivo: Explicar la Estrategia Integral para la Ampliación del Rol de Enfermería, con el fin de establecer la política de formación de recursos humanos e incorporar este nuevo rol al sistema público de salud en México. Metodología: Este documento describe cómo se realizó la Estrategia, su proceso de desarrollo y los componentes que la integran; así como el Marco Mexicano de Competencias para la Ampliación del Rol de Enfermería. Resultados: Se identificaron las acciones necesarias para la implementación de la Estrategia y se clasificaron en tres componentes: Laboral, Educativo/formación y Legal/normativo; así como los ejes transversales de Abogacía y Difusión. Discusión: Las estrategias para fortalecer el modelo de prestación de servicios de salud a nivel comunitario no han cambiado en muchos años. La implementación de la Estrategia proyecta la transformación hacia un modelo resolutivo donde los recursos humanos se desplieguen a la comunidad activamente. Conclusiones: La Estrategia busca adaptar la composición de la fuerza laboral en el Primer Nivel de Atención y optimizar su desempeño, para contribuir a mejorar la respuesta a las necesidades progresivas de salud.

ABSTRACT Introduction: Disparities between the burdens resulting from chronic illnesses and the corresponding responses by the health systems increase the inequalities in terms of coverture and effective access to the health services. In response to this situation, the Secretaría de Salud de México integrated diverse groups to work with the aim of designing strategies which can contribute to finding solutions to this problematic through the optimization and distribution of the nursing functions. Objective: To Inform on the Nursing Role Enhancement Integral Strategy in order to establish corresponding policies related to human resources formation, and incorporate this new role into the health public system in Mexico. Methodology: This document informs on how this Strategy was designed, its development process, and the components which integrate it, all within the Mexican Framework on Competencies to the Enhancement of the Nursing Role. Results: The needed actions to implement this Strategy were identified and further classified into three components: Work-related, Education-formation-related, and Legal-normative-related. Advocacy and Diffusion were determined as the transversal axes. Discussion: Strategies to strengthen the health service provision model in a community level have not changed in many years. The implementation of the Strategy, matter of this document, projects a transformation towards a resolutive model in that human resources are actively deployed into the community. Conclusions: This Strategy seeks adapting the composition of the primary healthcare working force and optimizing its performance in order to better address the health needs of the community.

RESUMO Introdução: Os desequilíbrios entre a carga de doenças crónicas e a resposta insuficiente do sistema de saúde, agudizam as desigualdades na cobertura e acesso efetivo aos serviços. O Secretaría de Salud integrou grupos de trabalho para traçar uma estratégia que contribua para a solução desta problemática, através da otimização e distribuição de funções de enfermagem. Objetivo: Explicar a Estratégia Integral para a Ampliação do Papel de Enfermagem, para estabelecer a política de formação de recursos humanos e incorporar este novo rolo ao sistema público de saúde no México. Metodologia: Este documento descreve como se realizou a Estratégia, seu processo de desenvolvimento e os componentes que a compõem, bem como o Quadro Mexicano de Competências para a Ampliação do Papel de Enfermagem. Resultados: Foram identificadas as ações necessárias para a implementação da Estratégia e classificaram-se em três componentes: Trabalhista, Educacional/formativo e Jurídica/normativo; bem como os eixos transversais de Advocacia e Difusão. Discussão: As estratégias para fortalecer o modelo de prestação de serviços de saúde a nível comunitário não cambiou em muitos anos. A implementação da Estratégia projeta a transformação para um modelo de resolução onde os recursos humanos ativamente direcionam-se à comunidade. Conclusões: A Estratégia busca adaptar a composição da força laboral no Primeiro Nível de Atenção e otimizar seu desempenho, para contribuir a melhorar a resposta às necessidades progressivas de saúde.

Transplantation of Human Neural Progenitor Cells (NPC) into Putamina of Parkinsonian Patients: A Case Series Study, Safety and Efficacy Four Years after Surgery.

Individuals with Parkinson's disease (PD) suffer from motor and mental disturbances due to degeneration of dopaminergic and non-dopaminergic neuronal systems. Although they provide temporary symptom relief, current treatments fail to control motor and non-motor alterations or to arrest disease progression. Aiming to explore safety and possible motor and neuropsychological benefits of a novel strategy to improve the PD condition, a case series study was designed for brain grafting of human neural progenitor cells (NPCs) to a group of eight patients with moderate PD. A NPC line, expressing Oct-4 and Sox-2, was manufactured and characterized. Using stereotactic surgery, NPC suspensions were bilaterally injected into patients' dorsal putamina. Cyclosporine A was given for 10 days prior to surgery and continued for 1 month thereafter. Neurological, neuropsychological, and brain imaging evaluations were performed pre-operatively, 1, 2, and 4 years post-surgery. Seven of eight patients have completed 4-year follow-up. The procedure proved to be safe, with no immune responses against the transplant, and no adverse effects. One year after cell grafting, all but one of the seven patients completing the study showed various degrees of motor improvement, and five of them showed better response to medication. PET imaging showed a trend toward enhanced midbrain dopaminergic activity. By their 4-year evaluation, improvements somewhat decreased but remained better than at baseline. Neuropsychological changes were minor, if at all. The intervention appears to be safe. At 4 years post-transplantation we report that undifferentiated NPCs can be delivered safely by stereotaxis to both putamina of patients with PD without causing adverse effects. In 6/7 patients in OFF condition improvement in UPDRS III was observed. PET functional scans suggest enhanced putaminal dopaminergic neurotransmission that could correlate with improved motor function, and better response to L-DOPA. Patients' neuropsychological scores were unaffected by grafting. Trial Registration: Fetal derived stem cells for Parkinson's disease https://doi.org/10.1186/ISRCTN39104513Reg#ISRCTN39104513.

In vitro modulation of Drimys winteri bark extract and the active compound polygodial on Salmo salar immune genes after exposure to Saprolegnia parasitica.

The rapid development of the aquaculture industry has global concerns with health management and control strategies to prevent and/or treat diseases and increase sustainability standards. Saprolegniosis is a disease caused by Saprolegnia parasitica, and is characterized by promoting an immunosuppression in the host. This study evaluated in vitro the extract and one active compound (polygodial) of Drimys winteri, a Chilean medicinal tree as a potential early immunostimulatory aid in Saprolegniosis control. Atlantic salmon (Salmo salar) head kidney cells (ASK-1) were incubated with both extract and pure polygodial before exposure to S. parasitica mycelium, and the expression of the immune-related genes interleukin 1ß (IL-1ß), interferon α (IFNα), and major histocompatibility complex II (MHCII) was evaluated. Both evidenced immunomodulatory capacities by increasing gene expressions. This immunomodulation related to a mitigatory action counteracting the immunosuppressing effects of S. parasitica. Despite that most immune-related genes were up-regulated, the down-regulation of MHCII, characteristic of S. parasitica infection, was lessened by pre-incubation with the compounds. This study provides the first insight on the potential of D. winteri bark extract as a possible immunomodulatory and defensive strategy against this oomycete infection in fish.

[Long-term cost-effectiveness of ticagrelor versus clopidogrel in acute coronary syndrome in Spain]. / Coste-efectividad a largo plazo de ticagrelor frente a clopidogrel en síndrome coronario agudo en España.

OBJECTIVE: To assess the cost-effectiveness relationship of Ticagrelor versus Clopidogrel for the management of acute coronary syndrome in Spain. METHODS: The data from the PLATO study were used for the calculation of the events rate and health-related quality of life for Ticagrelor and Clopidogrel for the first 12 months, whereas the costs were obtained from Spanish sources. Quality of life-adjusted survival and costs were estimated according to the fact that the patients did not suffer any thrombotic event (myocardial infarction or ictus) or this one was not fatal. The lifetime cots, life years gained, and the quality of life-adjusted survival were estimated for both treatment arms. Incremental cost-effectiveness ratios were assessed through the perspective of the Spanish healthcare system for 2013, by using a macro-costs strategy based on published literature and the survival tables for the Spanish population. RESULTS: Treatment with Ticagrelor was associated to an incremental cost of 1,228 Euros per year, an increase in 0.1652 life years gained, and 0.1365 years adjusted by quality of life, as compared to Clopidogrel. The cost for one quality of life-adjusted life year was 8,997 Euros and the cost per one gained life year of 7,435 . The sensitivity analysis showed consistent results. CONCLUSIONS: Treatment of acute coronary syndrome for 12 months with Ticagrelor was associated with a cost per 1 life year of quality of life-adjusted cost below the cost-effectiveness limits generally accepted in Spain.

OBJETIVO: Evaluar la relación coste-efectividad de ticagrelor frente a clopidogrel en el tratamiento del síndrome coronario agudo en España. MÉTODOS: Para el cálculo de la tasa de eventos y la calidad de vida relacionada con la salud para ticagrelor y clopidogrel durante los doce primeros meses se utilizaron los datos del estudio PLATO, mientras que los costes se obtuvieron de fuentes españolas. La supervivencia ajustada por calidad de vida y los costes se estimaron en función de que los pacientes no sufrieran ningún evento trombótico (infarto de miocardio o ictus) o éste fuese no mortal. El coste a lo largo de toda la vida, los años de vida ganados y la supervivencia por calidad de vida se estimaron para ambos brazos de tratamiento. Los ratios de coste-efectividad incremental se presentaron desde la perspectiva del sistema sanitario español en 2013, empleando una estrategia de macrocostes basada en la bibliografía publicada y utilizando las tablas de supervivencia de la población española. RESULTADOS: El tratamiento con ticagrelor se asoció con un coste incremental de 1.228 anuales, un aumento de 0,1652 años de vida ganados y 0,1365 años de vida ajustados por calidad comparado con clopidogrel. Se obtuvo un coste por año de vida ajustado por calidad de 8.997y un coste por año de vida ganado de 7.435 . El análisis de sensibilidad mostró resultados consistentes. CONCLUSIONES: El tratamiento durante 12 meses del síndrome coronario agudo con ticagrelor se asoció a un coste por año de vida ajustado por calidad por debajo de los límites de costeefectividad generalmente aceptados en España.

Coste-efectividad a largo plazo de ticagrelor frente a clopidogrel en síndrome coronario agudo en España / Long-term cost-effectiveness of ticagrelor versus clopidogrel in acute coronary syndrome in Spain

Objetivo: Evaluar la relación coste-efectividad de ticagrelor frente a clopidogrel en el tratamiento del síndrome coronario agudo en España. Métodos: Para el cálculo de la tasa de eventos y la calidad de vida relacionada con la salud para ticagrelor y clopidogrel durante los doce primeros meses se utilizaron los datos del estudio PLATO, mientras que los costes se obtuvieron de fuentes españolas. La supervivencia ajustada por calidad de vida y los costes se estimaron en función de que los pacientes no sufrieran ningún evento trombótico (infarto de miocardio o ictus) o éste fuese no mortal. El coste a lo largo de toda la vida, los años de vida ganados y la supervivencia por calidad de vida se estimaron para ambos brazos de tratamiento. Los ratios de coste-efectividad incremental se presentaron desde la perspectiva del sistema sanitario español en 2013, empleando una estrategia de macrocostes basada en la bibliografía publicada y utilizando las tablas de supervivencia de la población española. Resultados: El tratamiento con ticagrelor se asoció con un coste incremental de 1.228 euros anuales, un aumento de 0,1652 años de vida ganados y 0,1365 años de vida ajustados por calidad comparado con clopidogrel. Se obtuvo un coste por año de vida ajustado por calidad de 8.997 euros y un coste por año de vida ganado de 7.435 euros. El análisis de sensibilidad mostró resultados consistentes. Conclusiones: El tratamiento durante 12 meses del síndrome coronario agudo con ticagrelor se asoció a un coste por año de vida ajustado por calidad por debajo de los límites de coste-efectividad generalmente aceptados en España (AU)

Objective: To assess the cost-effectiveness relationship of Ticagrelor versus Clopidogrel for the management of acute coronary syndrome in Spain. Methods: The data from the PLATO study were used for the calculation of the events rate and health-related quality of life for Ticagrelor and Clopidogrel for the first 12 months, whereas the costs were obtained from Spanish sources. Quality of life-adjusted survival and costs were estimated according to the fact that the patients did not suffer any thrombotic event (myocardial infarction or ictus) or this one was not fatal. The lifetime cots, life years gained, and the quality of life-adjusted survival were estimated for both treatment arms. Incremental cost-effectiveness ratios were assessed through the perspective of the Spanish healthcare system for 2013, by using a macrocosts strategy based on published literature and the survival tables for the Spanish population. Results: Treatment with Ticagrelor was associated to an incremental cost of 1,228 euros per year, an increase in 0.1652 life years gained, and 0.1365 years adjusted by quality of life, as compared to Clopidogrel. The cost for one quality of life-adjusted life year was 8,997 euros and the cost per one gained life year of 7,435 euros. The sensitivity analysis showed consistent results. Conclusions: Treatment of acute coronary syndrome for 12 months with Ticagrelor was associated with a cost per 1 life year of quality of life-adjusted cost below the cost-effectiveness limits generally accepted in Spain (AU)

Indicencia de lesiones por accidente de trabajo según su localización anatómica y tipo de lesión ocurridos en España (1999-2001) / Incidence of occupational injuries by body part affected and type of injury in Spain, 1999-2001

Objetivo: Estudiar la evolución de las lesiones por accidentes de trabajo con baja en España en el período 1999 al 2001 según la naturaleza de la lesión y por la región anatómica afectada. Método: La información se refiere a los accidentes de trabajo con baja ocurridos a los trabajadores afiliados a la Seguridad Social que tienen cubierta dicha contingencia. El período de estudio ha sido los años 1999 al 2001. Los datos fueron obtenidos del Ministerio de Trabajo y Asuntos Sociales. Resultados: La naturaleza de la lesión más frecuente en los accidentes de trabajo con baja en los años estudiados ha sido "las torceduras, esguinces y distensiones", que coincide con la naturaleza de la lesión más frecuente en los accidentes leves de trabajo con baja. En cuanto a la naturaleza de la lesión más frecuente en los accidentes graves de trabajo con baja en los años del estudio ha sido "las fracturas". Y la naturaleza de la lesión más frecuente en los accidentes mortales de trabajo con baja fueron "las lesiones múltiples". En cuanto a la localización más frecuente del total de accidentes de trabajo con baja, de los accidentes leves de trabajo con baja y de los accidentes graves de trabajo con baja fueron las manos. En cuanto a los accidentes mortales de trabajo correspondió a las lesiones múltiples. Conclusiones: Sobre la base de los resultados obtenidos vemos que el tipo de lesión y su localización ha sido la misma en estos tres años, lo que nos indica que el riesgo sigue siendo el mismo y que se deberían tomar medidas preventivas que lo hicieran disminuir (AU)

Objetive: To study occupational injury trends in Spain in the period 1999 to 2001 by type of injury and body part affected. Method: The information refers to lost-time occupational injuries among workers in the Social Security system. The period of study included the years 1999 through 2001. The data were obtained from the Ministry of Labour and Social Affairs. Results: The most common type of injury was " twisting, sprains and strains", which is similar to that reported for mild lost-time occupational injuries. For serious accidents, the most frequent injury over the three-year study period was "fractures". For fatal occupational accidents during the three-year study period, the most common injury category was "multiple injuries" . For mild and serious accidents resulting in lost-time, the most frequently affected body part was the hand. In the case of fatal accidents, multiple body parts were most often involved. Conclusions: These results suggest that trends in type of injury and body part affected remained unchanged over these three years, indicating that similar risks persist and that control measures should be implemented in order to reduce this risk (AU)

Tubular hydrogen-bonded networks sustained by water molecules.

The design concept of functional solids relies on controlling the topology of crystal packing through exploitation of weak intermolecular forces. In the context of cyclic aggregates, the ability to anticipate the consequences of ring constituents and their stereochemistries on ring conformation is vitally important since even an apparently slight structural change effected on molecules can dramatically alter the crystal structure. We have found that solid-state structures formed by hydroxy acids with a general structure (+/-)-1 depend on steric interactions. Thus, with the exception of molecules 1b and 1e, compounds (+/-)-1a-(+/-)-1m, which possess bulky and conformationally rigid substituents, aggregate by forming tapes and sheets by alternating (+) and (-) subunits held together through carboxylic acid-to-alcohol hydrogen bonds. Homologue (+/-)-1n, with conformationally flexible substituents which allow conformational deformation, gives, by incorporation of molecules of water, an efficient hexagonal assembly which extends to the third dimension to form tubular H-bonding networks. Each puckered channel can be described as interconnected closely packed hexagons in chairlike conformations. The ethyl groups presented in (+/-)-1n gave the volume required to lock the inner hexagonal wall into a rigid structure. Attempts to obtain cyclic aggregates using small substituents, compounds (+/-)-1o-(+/-)-1q, failed. The observed supramolecular assemblies of the anhydrous compounds can be classified into one-dimensional strands and two-dimensional sheets, while three-dimensional networks are present only in the hydrated molecules (1b, 1e, and 1n). The crystal structure of the anhydrous (+/-)-1n compound confirms the important role played by water molecules in the formation of tubular structures.

Detection and significance of inapparent infection in Chagas disease in western Venezuela.

Inapparent infections of Trypanosoma cruzi were detected in symptomless seropositive people living in close proximity, and under the same conditions of risk, to patients with acute Chagas disease. Similar infections were also detected in sera samples of people from 25 villages of western Venezuela where Chagas disease is endemic. Seropositivity in all the 1,251 studied samples was established by use of 3 serological methods (direct agglutination test, indirect immunofluorescence antibody test, and enzyme-linked immunosorbent assay). Each seropositive sample was tested for detection of anti-T. cruzi-specific immunoglobulin (Ig) M and IgG levels and specific T. cruzi infection by molecular methodology (polymerase chain reaction assay). The combined analysis of the serologic (IgM and IgG levels), molecular (specific T. cruzi DNA), and statistical findings demonstrated the existence of a different stage of T. cruzi infection in asymptomatic patients, which is suggested to be recognized as inapparent infection. Its definition, significance, and comparison with typical Chagas disease phases are presented, and its potential epidemiological importance is discussed.

Analysis of genetic diversity of Trypanosoma cruzi: an application of riboprinting and gradient gel electrophoresis methods.

Analysis of restriction fragment length polymorphism (RFLP) profiles derived from digestion of polymerase chain reaction (PCR) products of the ribosomal 18S from Trypanosoma cruzi yields a typical 'riboprint' profile that can vary intraspecifically. A selection of 21 stocks of T. cruzi and three outgroup taxa: T. rangeli, T. conorhini and Leishmania braziliensis were analysed by riboprinting to assess divergence within and between taxa. T. rangeli, T. conorhini and L. braziliensis could be easily differentiated from each other and from T. cruzi. Phenetic analysis of PCR-RFLP profiles indicated that, with one or two exceptions, stocks of T. cruzi could be broadly partitioned into two groups that formally corresponded to T. cruzi I and T. cruzi II respectively. To test if ribosomal 18S sequences were homogeneous within each taxon, gradient gel electrophoresis methods were employed utilising either chemical or temperature gradients. Upon interpretation of the melting profiles of riboprints and a section of the 18S independently amplified by PCR, there would appear to be at least two divergent 18S types present within T. cruzi. Heterogeneity within copies of the ribosomal 18S within a single genome has therefore been demonstrated and interestingly, this dimorphic arrangement was also present in the outgroup taxa. Presumably the ancestral duplicative event that led to the divergent 18S types preceded that of speciation within this group. These divergent 18S paralogues may have, or had, different functional pressures or rates of molecular evolution. Whether or not these divergent types are equally transcriptionally active throughout the life cycle, remain to be assessed.

A synthetic hydroxy acid that shows tubular-shaped structure in solid-state and ionophoric activity in phospholipid bilayers

[formula: see text] In this contribution, we describe the ability of compound (+/-)-1b and six molecules of water to form in solid-state hexameric aggregates, which self-assemble to give hollow tubular structures. Single-crystal X-ray analysis shows that these tubes are open-ended, with irregular shape and internal van der Waals pore diameter between 6 and 9 A. In addition, transmembrane sodium transport activity was also assessed for (+/-)-1b using dynamic Na(+)-NMR technique.

Myocardial parasite persistence in chronic chagasic patients.

The persistence of Trypanosoma cruzi tissue forms was detected in the myocardium of seropositive individuals clinically diagnosed as chronic chagasic patients following endomyocardial biopsies (EMBs) processed by immunohistochemical (peroxidase-anti-peroxidase [PAP] staining) and molecular (polymerase chain reaction [PCR]) techniques. An indirect immunofluorescent technique revealed antigenic deposits in the cardiac tissue in 24 (88.9%) of 27 patients. Persistent T. cruzi amastigotes were detected by PAP staining in the myocardium of 22 (84.6%) of 26 patients. This finding was confirmed with a PCR assay specific for T. cruzi in 21 (91.3%) of 23 biopsy specimens from the same patients. Statistical analysis revealed substantial agreement between PCR and PAP techniques (k = 0.68) and the PCR and any serologic test (k = 0.77). The histopathologic study of EMB specimens from these patients revealed necrosis, inflammatory infiltrates, and fibrosis, and made it possible to detect heart abnormalities not detected by electrocardiogram and/or cineventriculogram. These indications of myocarditis were supported by the detection of T. cruzi amastigotes by the PAP technique or its genome by PCR. They suggest that although the number of parasites is low in patients with chronic Chagas' disease, their potential for heart damage may be comparable with those present during the acute phase. The urgent necessity for testing new drugs with long-term effects on T. cruzi is discussed in the context of the present results.

Acute Chagas' disease in western Venezuela: a clinical, seroparasitologic, and epidemiologic study.

A clinical, parasitologic, and serologic study carried out between 1988 and 1996 on 59 acute-phase patients in areas of western Venezuela where Chagas' disease is endemic showed 19 symptomatic patterns or groups of symptoms appearing in combination with different frequencies. The symptomatic pattern with the highest frequency was that showing simultaneously fever, myalgia, headache, and Romaña's sign, which was detected in 20% of the acute-phase patients. Asymptomatic individuals and patients with fever as the only sign of the disease made up 15% and 11.9% of the total acute cases, respectively. Statistical correlation analysis revealed that xenodiagnosis and hemoculture were the most reliable and concordant of the five parasitologic methods used; these two methods also showed the highest proportions in detecting any clinical symptomatic pattern in acute-phase patients. A similar high reliability and concordance was obtained with a direct agglutination test, an indirect immunofluorescent antibody test, and an ELISA as serologic tests, which also showed a higher proportion of positive detection of clinical patterns than parasitologic methods (P < 0.001). It is recommended that individuals coming from endemic areas showing mild and/or severe clinical manifestations should be suspected of being in contact or having been in contact with Trypanosoma cruzi, be referred for parasitologic and serologic evaluations to confirm the presumptive clinical diagnosis of acute Chagas' disease, and start specific treatment. The epidemiologic implications of the present findings are discussed and the use of similar methodology to evaluate other areas where Chagas' disease is endemic is suggested.

On the molecular taxonomy of Trypanosoma cruzi using riboprinting.

In order to investigate the molecular taxonomy within Trypanosoma cruzi, the ribosomal small subunit (18S) gene was amplified by polymerase chain reaction (PCR) from a selection of 21 stocks and 3 outgroup taxa. Amplification products were digested with 10 restriction enzymes; restriction fragments were separated by polyacrylamide gel electrophoresis and profiles were visualized by silver staining. Upon analysis of such riboprint profiles, an estimate of pairwise phenetic distance between stocks of T. cruzi was calculated. Upon principal coordinate analysis of this data matrix, a tendency towards a bi-polar grouping of stocks was observed. These 2 groups were predominantly either zymodeme 1 stocks or zymodeme 2 stocks. The position of zymodeme 3 stocks remained intermediate between the 2 groups but did not form a coherent group by themselves. It would therefore appear premature to warrant division of T. cruzi into 2 discrete taxa or subspecies until the relationships of further zymodeme 3 stocks are elucidated.

Temperature gradient gel electrophoresis (TGGE) analysis of riboprints from Trypanosoma cruzi.

To test the homogeneity of 18S sequences within Trypanosoma cruzi, riboprint profiles were separated by temperature gradient gel electrophoresis (TGGE). Upon interpretation of melting curves of fragments within a riboprint profile, there appeared to be two 18S sequence types within each stock examined. Two similar types were also observed within outgroup taxa Trypanosoma conorhini, Trypanosoma rangeli and Leishmania braziliensis. From DNA hybridization studies, these fragments were shown to have homology to the 18S V1 region. There are therefore two 18S V1 regions, differing in sequence, present in all taxa examined. When only a single 18S sequence is used to represent each taxa for phylogenetic inference, comparisons may be between paralogous and not orthologous copies of this region, such that, inferred relationships may merely reflect a gene history. This seriously questions the current molecular phylogeny of these protozoa using 18S data.

Random amplification of polymorphic DNA as a tool for taxonomic studies of triatomine bugs (Hemiptera: Reduviidae).

Eleven of 27 decameric primers were found to be suitable for random amplification of polymorphic DNA (RAPD) from triatomine bugs on the basis that they produced discrete profiles and distinguished among Panstrongylus megistus (Burmeister), Rhodnius prolixus Stål, and Triatoma infestans (Klug). The legs, or single leg segments, of individual bugs were used as the source of DNA so that the taxonomic value of the bug was conserved. Within the scope of the specimens studied, RAPD profiles allowed assignment to species even when bugs were kept dry for up to 12 mo. Profiles for individuals within a species were not identical. RAPD profiles, with the specimens tested, distinguished among species of 3 pairs considered to be morphologically similar and closely related, namely, Rhodnius ecuadorensis Lent & León and Rhodnius pictipes Stål; Rhodnius nasutus Stål, and Rhodnius neglectus Lent; Rhodnius prolixus Stål and Rhodnius robustus Larrousse. RAPD data conformed with the perceived affinities among these species. RAPD polymorphisms were seen with T. infestans from 3 different localities, but none of the polymorphisms was confined to 1 source. RAPD provided a molecular basis to reassess taxonomic relationships within the Triatomine subfamily. The accurate distinction of triatomine species and of intraspecific bug populations may contribute to elimination of vector-borne Chagas disease from the Americas.

Chagas disease in the Amazon Basin: association of Panstrongylus geniculatus (Hemiptera: Reduviidae) with domestic pigs.

Just over 100 autochthonous cases of Chagas disease are reported from the Brazilian Amazon Basin. Panstrongylus geniculatus (Latreille) occurs throughout the region and is the known vector of Trypanosoma cruzi, principal zymodeme 3 (Z3) to the armadillo Dasypus novemcinctus. In the small riverine community of Furo do Rio Pau Grande, pigsties adjoining houses were heavily infested with P. geniculatus, which repeatedly attacked local inhabitants. Palm trees in the immediate vicinity were also infested. T. cruzi principal zymodeme 1 (Z1) was isolated from P. geniculatus, domestic pigs, and opossums, but no human infections were detected. The threat of endemic Chagas disease to the Amazon Basin from either domiciliation of local silvatic triatomine species, or from migration of domestic vectors, demands a program of vigilance and plans of action to eliminate household triatomine colonies.

Two-phase study of hepatic artery vascular occlusion with microencapsulated cisplatin in patients with liver metastases from neuroendocrine tumors.

OBJECTIVE: We conducted a two-phase trial in which 100-micron polylactic acid microcapsules with a cisplatin payload (manufactured at our institution [the M. D. Anderson Cancer Center]) were used for hepatic artery occlusion therapy for symptomatic patients who had liver metastases from neuroendocrine tumors. SUBJECTS AND METHODS: Between January 1993 and December 1995, 20 patients with advanced, unresectable, symptomatic neuroendocrine tumors with liver metastases received repeated hepatic artery occlusion therapy using encapsulated cisplatin. The dose of encapsulated cisplatin was increased in a stepwise fashion. Selective angiography was used to occlude the portion of the hepatic vasculature that had the most metastases with encapsulated cisplatin microcapsules. In each patient, hepatic artery occlusion therapy was repeated in 6-8 weeks and responses were evaluated. Subsequent vascular occlusions were performed on the basis of the level of palliation achieved and the persistence of symptoms. RESULTS: Of the 20 patients, 17 patients had carcinoid tumors and three had islet cell tumors. The median percentage of liver replacement was approximately 50%. Fifteen of the 20 patients had received prior therapy and 17 patients had hormonal syndrome at the beginning of therapy. One patient had tumor bulk-related symptoms. Nineteen patients had elevated peptides markers that could be followed serially Six patients received encapsulated cisplatin at 50 mg/m2, four patients at 75 mg/m2, and 10 patients at 100 mg/m2 of body surface area. The median number of vascular occlusive procedures per patient was three. All patients were assessable for toxicity and 18 were assessable for response (the other two patients were not assessable because of loss of follow-up). The median follow-up time was 14 months. Twelve (67%) of 18 patients had a median reduction in symptoms of 50%. Eleven (73%) of 15 patients with elevated 24-hr-urine levels of 5-hydroxyindoleacetic acid had a median reduction of 64% for this symptom. We observed objective reduction in the tumors of 14 of the 18 patients. In six of the 14 patients, we noted a partial response. In eight, we observed a minor response. In four of the 18 patients, we noted no response. One treatment-related death resulted from hepatorenal syndrome. Other major complications included hepatic pain (100%), fever (100%), nausea (100%), and vomiting (95%). Also all patients had a transient elevation of liver enzymes. Five of the 20 patients died of disease during our study. CONCLUSION: Hepatic artery vascular occlusion therapy using encapsulated cisplatin is feasible, can palliate symptoms, and can produce biochemical and objective responses in liver metastases from neuroendocrine tumors. The maximum tolerated dose appears to be 100 mg/m2 of body surface area per treatment. Polylactic acid capsules have potential because they can incorporate multiple agents. With surface coating, such capsules can also be used to target specific receptors.

[Clinical, parasitological and histopathologic follow-up studies of acute Chagas patients treated with benznidazole]. / Seguimiento clínico, parasitológico e histopatológico de pacientes chagásicos agudos tratados con benznidazol.

With the purpose of studying their clinical and histopathologic evolution, 10 acute chagasic patients with myocarditis diagnosed by endomyocardial biopsy and positive sero-parasitologic methods were evaluated at 11 months (8-21 months) after treatment with oral benznidazole. Four of them were reevaluated 5 years post-treatment (58-68 months). Study protocol consisted of clinical, hemodynamic, echocardiographic, seroparasitologic and histopathologic evaluations. Results showed evidence of persisting myocarditis in 90% and 75% of patients evaluated at 11 months and 5 years respectively, along with asymptomatic, subclinical left ventricular systolic dysfunction being recognized in 75% of patients evaluated 5 years after treatment. All parasitologic studies became negative during follow-up, but serology remained positive for Trypanosoma cruzi antibodies in 80% and 75% of patients studied at 11 months and 5 years. In conclusion, myocardial damage was constantly found in our acute chagasic patients. Treatment with benznidazole eliminated symptoms and parasitemia, but it does not seem to alter favorably the histopathological evolution of the chagasic cardiac disease.

Biochemical characterization of myocardial damage in chronic Chagas' disease.

BACKGROUND: In the early asymptomatic stages of cardiomyopathy in chronic Chagas' disease, septal endomyocardial biopsies disclose multiple evidence of evolving myocardial damage. Detection of signs of an active myocardiopathic process may allow a better understanding of the evolution of this and other related dilated cardiomyopathies and provide a means for evaluation of the result of future therapeutic schemes. HYPOTHESIS: This study was designed to explore whether cellular damage caused by Chagas' disease is reflected by changes of certain serum electrolytes, enzymes, and glycoproteins associated with myocardial metabolism, especially in the coronary sinus into which the blood just metabolized by the heart is drained. METHODS: The study included 47 patients (35 men and 12 women, average age 40 years) with positive complement fixation reaction and hemagglutination test for Chagas' disease. The study protocol included medical records, electrocardiographic (ECG) recordings, routine laboratory analysis, chest x-rays, noninvasive cardiac examinations, and cardiac catheterization. RESULTS: In this study, we determined the concentration or activity of 9 electrolytes, 5 glycoprotein fractions, and 12 enzymes related to cardiac metabolism in blood from the coronary sinus, the superior vena cava, the pulmonary and femoral arteries, and found early release of inorganic phosphorus (p < 0.01) and isocitrate dehydrogenase (p < 0.01) from the heart and increased activity of serum alkaline phosphatase and aldolase (p < 0.05). Discriminant analysis suggested that the combination of the clinical picture, electrocardiographic findings, and peripheral activity of serum aldolase might be useful for the recognition of 86% of patients with Chagas' disease without segmental myocardial damage, 80% of those with early segmental abnormalities, and all patients with advanced myocardial damage or congestive heart failure. CONCLUSION: These results would make the application of more invasive techniques, such as left cineventriculography for detection of early myocardial compromise, unnecessary.