Dedifferentiated Low-Grade Osteosarcoma, Outcome with or Without Chemotherapy: A Systematic Review.

The treatment of low-grade osteosarcomas is surgical resection with wide margins. In instances of dedifferentiation, a therapeutic paradigm similar to that of conventional high-grade osteosarcoma has not been adequately evaluated in these neoplasms. The main objective of this review was to define whether the addition of chemotherapy to surgical treatment has an impact on the survival of patients with dedifferentiated low-grade osteosarcomas. Secondary objectives were to observe the degree of histological response to neoadjuvant chemotherapy and to describe the percentage of de novo dedifferentiation. A systematic search of articles including dedifferentiated low-grade osteosarcomas, published between 1980 and 2022 was carried out in the PubMed, Cochrane and Scielo databases. A qualitative synthesis of the results was performed. Twenty-three articles comprising 117 patients were included. The survival of patients treated with surgery alone and surgery with chemotherapy was not statistically significant between the two groups. A good histological response was seen in 20% of specimens treated with neoadjuvant chemotherapy. De novo dedifferentiation was seen in approximately a fifth of low-grade osteosarcomas. The evidence available suggests that the addition of chemotherapy does not have an impact on the survival of patients with low-grade dedifferentiated osteosarcomas.

Developmental or adult-onset deletion of neurotensin receptor-1 from dopamine neurons differentially reduces body weight.

Central neurotensin signaling via neurotensin receptor-1 (NtsR1) modulates various aspects of physiology, including suppressing feeding and promoting locomotor activity that can support weight loss. However, it remains unclear when and where NtsR1 expression contributes to control of body weight vs. other effects. We previously showed that activating ventral tegmental area (VTA) dopamine (DA) neurons that express NtsR1 promotes weight loss. We therefore hypothesized that deleting NtsR1 from DA neurons would promote weight gain by increasing food intake and decreasing physical activity. In contrast, developmental deletion of NtsR1 from DA neurons (by crossing DATCre mice with NtsR1flox/flox mice) had no impact on the feeding or body weight of mice fed a chow diet, though it augmented locomotor activity. Developmental deletion of NtsR1 from DA neurons protected mice from diet-induced obesity, but not via altering feeding, physical activity, or energy expenditure. Given that NtsR1 may exert distinct roles within development vs. adulthood, we then examined the impact of adult-onset deletion of NtsR1 from VTA DA neurons. We injected adult NtsR1flox/flox mice in the VTA with adeno associated virus to Cre-dependently delete NtsR1 in the VTA (VTAR1Null mice) and compared them to mice with intact NtsR1 (Controls). Again, in contrast to our hypothesis, VTAR1Null mice gained less weight than Controls while on normal chow or high fat diets. Moreover, VTAR1Null mice exhibited blunted feeding after fasting, suggesting a role for NtsR1 in adult VTA DA neurons in coordinating energy need and intake. Altogether, these data suggest that intact expression of NtsR1 in DA neurons is necessary for appropriate regulation of body weight, but a lack of NtsR1 in the developing vs. adult DA system protects from weight gain via different mechanisms. These findings emphasize the need for temporal and site-specific resolution to fully understand the role of NtsR1 within the brain.

Competencies for quality spiritual care in palliative care in Latin America: from the Spirituality Commission of the Latin American Association for Palliative Care.

Spiritual care is an essential part of quality palliative care. However, the literature regarding spiritual care competencies in Latin America is limited. Herein we propose the basic quality standards for spiritual care in palliative care according to best professional practices and provide a common vocabulary and required competencies for quality clinical spiritual care. Both elements, quality standards and a common vocabulary, are part of an essential step implementing continuous educational initiatives among interdisciplinary palliative care teams in Latin America. Members of the Spirituality Commission of the Latin American Association for Palliative Care and three members of independent professional palliative care organizations identified and reviewed our proposed spiritual care competencies and created a consensus document describing the competencies for general spiritual care. In the context of palliative care in Latin America, general spiritual care is provided by members of interdisciplinary teams. We proposed six competencies for high-quality general spiritual care and their observable behaviors that every member of an interdisciplinary palliative care team should have to provide quality clinical spiritual care in their daily practice: (I) personal, spiritual, and professional development; (II) ethics of spiritual care; (III) assessment of spiritual needs and spiritual care interventions; (IV) empathic and compassionate communication; (V) supportive and collaborative relationships among the interdisciplinary team; and (VI) inclusivity and diversity.

Activation of ventral tegmental area neurotensin Receptor-1 neurons promotes weight loss.

Dopamine (DA) neurons in the ventral tegmental area (VTA) modulate physical activity and feeding behaviors that are disrupted in obesity. Yet, the heterogeneity of VTA DA neurons has hindered determination of which ones might be leveraged to support weight loss. We hypothesized that increased activity in the subset of VTA DA neurons expressing neurotensin receptor-1 (NtsR1) might promote weight loss behaviors. To test this, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to activate VTA NtsR1 neurons in normal weight and diet-induced obese mice. Acute activation of VTA NtsR1 neurons (24hr) significantly decreased body weight in normal weight and obese mice by reducing food intake and increasing physical activity. Moreover, daily activation of VTA NtsR1 neurons in obese mice sustained weight loss over 7 days. Activating VTA NtsR1 neurons also suppressed how much mice worked to obtain sucrose rewards, even when there was high motivation to consume. However, VTA NtsR1 neural activation was not reinforcing, nor did it invoke liabilities associated with whole-body NtsR1 agonism such as anxiety, vasodepressor response or hypothermia. Activating VTA NtsR1 neurons therefore promotes dual behaviors that support weight loss without causing adverse effects, and is worth further exploration for managing obesity.

Lateral hypothalamic area neuropeptides modulate ventral tegmental area dopamine neurons and feeding.

Understanding how the brain coordinates energy status with the motivation to eat is crucial to identify strategies to improve disordered body weight. The ventral tegmental area (VTA), known as the core of the mesolimbic system, is of particular interest in this regard because it controls the motivation to consume palatable, calorie-dense foods and to engage in volitional activity. The VTA is largely composed of dopamine (DA) neurons, but modulating these DA neurons has been alternately linked with promoting and suppressing feeding, suggesting heterogeneity in their function. Subsets of VTA DA neurons have recently been described based on their anatomical distribution, electrophysiological features, connectivity and molecular expression, but to date there are no signatures to categorize how DA neurons control feeding. Assessing the neuropeptide receptors expressed by VTA DA neurons may be useful in this regard, as many neuropeptides mediate anorexic or orexigenic responses. In particular, the lateral hypothalamic area (LHA) releases a wide variety of feeding-modulating neuropeptides to the VTA. Since VTA neurons intercept LHA neuropeptides known to either evoke or suppress feeding, expression of the cognate neuropeptide receptors within the VTA may point to VTA DA neuronal mechanisms to promote or suppress feeding, respectively. Here we review the role of the VTA in energy balance and the LHA neuropeptide signaling systems that act in the VTA, whose receptors might be used to classify how VTA DA neurons contribute to energy balance.

Mapping the populations of neurotensin neurons in the male mouse brain.

Neurotensin (Nts) is a neuropeptide implicated in the regulation of many facets of physiology, including cardiovascular tone, pain processing, ingestive behaviors, locomotor drive, sleep, addiction and social behaviors. Yet, there is incomplete understanding about how the various populations of Nts neurons distributed throughout the brain mediate such physiology. This knowledge gap largely stemmed from the inability to simultaneously identify Nts cell bodies and manipulate them in vivo. One means of overcoming this obstacle is to study NtsCre mice crossed onto a Cre-inducible green fluorescent reporter line (NtsCre;GFP mice), as these mice permit both visualization and in vivo modulation of specific populations of Nts neurons (using Cre-inducible viral and genetic tools) to reveal their function. Here we provide a comprehensive characterization of the distribution and relative densities of the Nts-GFP populations observed throughout the male NtsCre;GFP mouse brain, which will pave the way for future work to define their physiologic roles. We also compared the distribution of Nts-GFP neurons with Nts-In situ Hybridization (Nts-ISH) data from the adult mouse brain. By comparing these data sets we can distinguish Nts-GFP populations that may only transiently express Nts during development but not in the mature brain, and hence which populations may not be amenable to Cre-mediated manipulation in adult NtsCre;GFP mice. This atlas of Nts-GFP neurons will facilitate future studies using the NtsCre;GFP line to describe the physiological functions of individual Nts populations and how modulating them may be useful to treat disease.

Latin American and Caribbean consensus on noninvasive central nervous system neuromodulation for chronic pain management (LAC2-NIN-CP).

INTRODUCTION: Chronic pain (CP) is highly prevalent and generally undertreated health condition. Noninvasive brain stimulation may contribute to decrease pain intensity and influence other aspects related to CP. OBJECTIVE: To provide consensus-based recommendations for the use of noninvasive brain stimulation in clinical practice. METHODS: Systematic review of the literature searching for randomized clinical trials followed by consensus panel. Recommendations also involved a cost-estimation study. RESULTS: The systematic review wielded 24 transcranial direct current stimulation (tDCS) and 22 repetitive transcranial magnetic stimulation (rTMS) studies. The following recommendations were provided: (1) Level A for anodal tDCS over the primary motor cortex (M1) in fibromyalgia, and level B for peripheral neuropathic pain, abdominal pain, and migraine; bifrontal (F3/F4) tDCS and M1 high-definition (HD)-tDCS for fibromyalgia; Oz/Cz tDCS for migraine and for secondary benefits such as improvement in quality of life, decrease in anxiety, and increase in pressure pain threshold; (2) level A recommendation for high-frequency (HF) rTMS over M1 for fibromyalgia and neuropathic pain, and level B for myofascial or musculoskeletal pain, complex regional pain syndrome, and migraine; (3) level A recommendation against the use of anodal M1 tDCS for low back pain; and (4) level B recommendation against the use of HF rTMS over the left dorsolateral prefrontal cortex in the control of pain. CONCLUSION: Transcranial DCS and rTMS are recommended techniques to be used in the control of CP conditions, with low to moderate analgesic effects, and no severe adverse events. These recommendations are based on a systematic review of the literature and a consensus made by experts in the field. Readers should use it as part of the resources available to decision-making.

Identification of Neurotensin Receptor Expressing Cells in the Ventral Tegmental Area across the Lifespan.

Neurotensin (Nts) promotes activation of dopamine (DA) neurons in the ventral tegmental area (VTA) via incompletely understood mechanisms. Nts can signal via the G protein-coupled Nts receptors 1 and 2 (NtsR1 and NtsR2), but the lack of methods to detect NtsR1- and NtsR2-expressing cells has limited mechanistic understanding of Nts action. To overcome this challenge, we generated dual recombinase mice that express FlpO-dependent Cre recombinase in NtsR1 or NtsR2 cells. This strategy permitted temporal control over recombination, such that we could identify NtsR1- or NtsR2-expressing cells and determine whether their distributions differed between the developing and adult brain. Using this system, we found that NtsR1 is transiently expressed in nearly all DA neurons and in many non-DA neurons in the VTA during development. However, NtsR1 expression is more restricted within the adult brain, where only two thirds of VTA DA neurons expressed NtsR1. By contrast, NtsR2 expression remains constant throughout lifespan, but it is predominantly expressed within glia. Anterograde tract tracing revealed that NtsR1 is expressed by mesolimbic, not mesocortical DA neurons, suggesting that VTA NtsR1 neurons may represent a functionally unique subset of VTA DA neurons. Collectively, this work reveals a cellular mechanism by which Nts can directly engage NtsR1-expressing DA neurons to modify DA signaling. Going forward, the dual recombinase strategy developed here will be useful to selectively modulate NtsR1- and NtsR2-expressing cells and to parse their contributions to Nts-mediated behaviors.

Most Relevant Neuropathic Pain Treatment and Chronic Low Back Pain Management Guidelines: A Change Pain Latin America Advisory Panel Consensus.

Objective: Chronic pain conditions profoundly affect the daily living of a significant number of people and are a major economic and social burden, particularly in developing countries. The Change Pain Latin America (CPLA) advisory panel aimed to identify the most appropriate guidelines for the treatment of neuropathic pain (NP) and chronic low back pain (CLBP) for use across Latin America. Methods: Published systematic reviews or practice guidelines were identified by a systematic search of PubMed, the Guidelines Clearinghouse, and Google. Articles were screened by an independent reviewer, and potential candidate guidelines were selected for more in-depth review. A shortlist of suitable guidelines was selected and critically evaluated by the CPLA advisory panel. Results: Searches identified 674 and 604 guideline articles for NP and CLBP, respectively. Of these, 14 guidelines were shortlisted for consensus consideration, with the following final selections made: "Recommendations for the pharmacological management of neuropathic pain from the Neuropathic Pain Special Interest Group in 2015-pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis.""Diagnosis and treatment of low back pain: A joint clinical practice guideline from the American College of Physicians and the American Pain Society" (2007). Conclusions: The selected guidelines were endorsed by all members of the CPLA advisory board as the best fit for use across Latin America. In addition, regional considerations were discussed and recorded. We have included this expert local insight and advice to enhance the implementation of each guideline across all Latin American countries.

Lateral Hypothalamic Neurotensin Neurons Orchestrate Dual Weight Loss Behaviors via Distinct Mechanisms.

The central mechanism by which neurotensin (Nts) potentiates weight loss has remained elusive. We leveraged chemogenetics to reveal that Nts-expressing neurons of the lateral hypothalamic area (LHA) promote weight loss in mice by increasing volitional activity and restraining food intake. Intriguingly, these dual weight loss behaviors are mediated by distinct signaling pathways: Nts action via NtsR1 is essential for the anorectic effect of the LHA Nts circuit, but not for regulation of locomotor or drinking behavior. Furthermore, although LHA Nts neurons cannot reduce intake of freely available obesogenic foods, they effectively restrain motivated feeding in hungry, weight-restricted animals. LHA Nts neurons are thus vital mediators of central Nts action, particularly in the face of negative energy balance. Enhanced action via LHA Nts neurons may, therefore, be useful to suppress the increased appetitive drive that occurs after lifestyle-mediated weight loss and, hence, to prevent weight regain.

Synthesis of acyl-hydrazone from usnic acid and isoniazid and its anti-Mycobacterium tuberculosis activity / Síntesis de acil-hidrazona a partir del ácido úsnico e isoniazida y su actividad anti-Mycobacterium tuberculosis / Síntese de acilhidrazona a partir de ácido úsnico e isoniazida e sua atividade anti-Mycobacterium tuberculosis

Abstract Compound usnic acid (1), isolated from lichen Evernia prunastri (Cajamarca-Peru) and the synthesis and characterization of its acyl-hydrazone (2), from the condensation reaction between usnic acid and isoniazid in an ethanol solution under reflux, giving an overall yield of 95%, were evaluated. Both compounds were evaluated and compared with isoniazid according to its anti-Mycobacterium tuberculosis activity based on the tetrazolium microplate assay (TEMA). Compound 1 had MIC (minimal inhibitory concentration) value of 16.0 μg/mL in each test of H37Rv (susceptible type), TB DM 97 (resistant wild type) and MDR DM 1098 (multi drug resistances type) strains. In similar tests, compound 2 MIC values were 2.0, 64.0 and 64.0 μg/mL respectively.

Resumen Se evaluó el ácido úsnico (1), aislado del liquen Evernia prunastri (Cajamarca-Perú), producto natural conocido por sus actividades biológicas, y, del mismo modo, se evaluó la síntesis de su derivado acil-hidrazona (2), obtenido a partir de una reacción de condensación entre el ácido úsnico y la isoniazida en solución etanólica a reflujo, con un rendimiento global de 95%. Ambos compuestos fueron evaluados y comparados con la isoniazida según su actividad anti-Mycobacterium tuberculosis basada en el ensayo de susceptibilidad mediante el método TEMA. Los resultados mostraron que el compuesto 1 presenta valores de MIC de 16,0 μg/mL frente a las cepas H37Rv, TB DM 97 y MDR DM 1098, mientras que el compuesto 2 presenta valores de MIC de 2,0; 64,0 y 64,0 μg/mL respectivamente.

Resumo Foi avaliado o ácido úsnico (1), um produto natural conhecido pelas suas atividades biológicas, isolado a partir do líquen Evernia prunastri (Cajamarca-Peru), assim mesmo foi avaliada a síntese do seu derivado, a acil-hidrazona (2), obtido a partir de uma reação de condensação com refluxo entre o ácido úsnico e a isoniazida em solução etanólica, com um rendimento global de 95%. A atividade anti-Mycobacterium tuberculosis de ambos compostos foi avaliada e comparada com a isoniazida mediante testes de sensibilidade obtidos pelo método TEMA. Os resultados mostraram que o composto 1 apresenta o valor de MIC de 16,0 μg/mL contra variedades H37Rv, TB DM 97 e MDR DM 1098; enquanto que para o composto 2 os valores de MIC são de 2,0; 64,0 e 64,0 μg/mL, respectivamente.

Optimizing post-operative pain management in Latin America / Aprimorar o controle da dor no pós-operatório na América Latina

Abstract Post-operative pain management is a significant problem in clinical practice in Latin America. Insufficient or inappropriate pain management is in large part due to insufficient knowledge, attitudes and education, and poor communications at various levels. In addition, the lack of awareness of the availability and importance of clear policies and guidelines for recording pain intensity, the use of specific analgesics and the proper approach to patient education have led to the consistent under-treatment of pain management in the region. However, these problems are not insurmountable and can be addressed at both the provider and patient level. Robust policies and guidelines can help insure continuity of care and reduce unnecessary variations in practice. The objective of this paper is to call attention to the problems associated with Acute Post-Operative Pain (APOP) and to suggest recommendations for their solutions in Latin America. A group of experts on anesthesiology, surgery and pain developed recommendations that will lead to more efficient and effective pain management. It will be necessary to change the knowledge and behavior of health professionals and patients, and to obtain a commitment of policy makers. Success will depend on a positive attitude and the commitment of each party through the development of policies, programs and the promotion of a more efficient and effective system for the delivery of APOP services as recommended by the authors of this paper. The writing group believes that implementation of these recommendations should significantly enhance efficient and effective post-operative pain management in Latin America.

Resumo O controle da dor no período pós-operatório é um problema significativo na prática clínica na América Latina. O controle insuficiente ou inadequado da dor é devido, em grande parte, à insuficiência de conhecimento, atitudes e formação e à comunicação precária em vários níveis. Além disso, a falta de conscientização da disponibilidade e importância de políticas e diretrizes inequívocas para avaliar a intensidade da dor, o uso de analgésicos específicos e a abordagem adequada para instruir o paciente levaram ao subtratamento consistente da dor na região. Contudo, esses problemas não são insuperáveis e podem ser abordados no âmbito tanto do provedor quanto do paciente. Políticas e diretrizes substanciais podem ajudar a garantir a continuidade dos cuidados e reduzir as variações desnecessárias na prática. O objetivo deste artigo é chamar a atenção para os problemas associados à dor aguda no pós-operatório (DAPO) e sugerir recomendações para solucioná-los na América Latina. Um grupo de especialistas em anestesiologia, cirurgia e dor desenvolveu recomendações que levarão a um controle mais eficiente e eficaz da dor. Será preciso mudar o conhecimento e o comportamento dos profissionais de saúde e pacientes e obter um compromisso por parte de legisladores. O sucesso dependerá de uma atitude positiva e do compromisso de cada parte através do desenvolvimento de políticas e programas e da promoção de um sistema mais eficiente e eficaz para a prestação de serviços para a DAPO, como recomendado pelos autores deste trabalho. O grupo que as redigiu acredita que a aplicação dessas recomendações deve melhorar de modo significativo a eficiência e eficácia do controle da dor no período pós-operatório na América Latina.

[Optimizing post-operative pain management in Latin America]. / Aprimorar o controle da dor no pós­operatório na América Latina.

Post-operative pain management is a significant problem in clinical practice in Latin America. Insufficient or inappropriate pain management is in large part due to insufficient knowledge, attitudes and education, and poor communications at various levels. In addition, the lack of awareness of the availability and importance of clear policies and guidelines for recording pain intensity, the use of specific analgesics and the proper approach to patient education have led to the consistent under-treatment of pain management in the region. However, these problems are not insurmountable and can be addressed at both the provider and patient level. Robust policies and guidelines can help insure continuity of care and reduce unnecessary variations in practice. The objective of this paper is to call attention to the problems associated with Acute Post-Operative Pain (APOP) and to suggest recommendations for their solutions in Latin America. A group of experts on anesthesiology, surgery and pain developed recommendations that will lead to more efficient and effective pain management. It will be necessary to change the knowledge and behavior of health professionals and patients, and to obtain a commitment of policy makers. Success will depend on a positive attitude and the commitment of each party through the development of policies, programs and the promotion of a more efficient and effective system for the delivery of APOP services as recommended by the authors of this paper. The writing group believes that implementation of these recommendations should significantly enhance efficient and effective post-operative pain management in Latin America.

Use of Opioids in Latin America: The Need of an Evidence-Based Change.

OBJECTIVE: The subject of this publication has been focused on local considerations for facilitating regional best practice, including identifying and uniformly adopting the most relevant international guidelines on opioid use (OU) in chronic pain management. DESIGN AND SETTING: The Change Pain Latin America (CPLA) Advisory Panel conducted a comprehensive, robust, and critical analysis of published national and international reviews and guidelines of OU, considering those most appropriate for Latin America. METHODS: A PubMed search was conducted using the terms "opioid," "chronic," and "pain" and then refined using the filters "practice guidelines" and "within the last 5 years" (2007-2012). Once the publications were identified, they were selected using five key criteria: "Evidence based," "Comprehensive," "From a well-recognized source," "Current publications," and "Based on best practice" and then critically analyzed considering 10 key criteria for determining the most relevant guidelines to be applied in Latin America. RESULTS: The initial PubMed search identified 177 reviews and guidelines, which was reduced to 16 articles using the five preliminary criteria. After a secondary analysis according to the 10 key criteria specific to OU in Latin America, 10 publications were selected for critical review and discussion. CONCLUSIONS: The CPLA advisory panel considered the "Safe and effective use of opioids for chronic non-cancer pain" (published in 2010 by the NOUGG of Canada) to be valid, relevant to Latin America, practical, evidence-based, concise, unambiguous, and sufficiently educational to provide clear instruction on OU and pain management and, thus, recommended for uniform adoption across the Latin America region.

Technology in MicroRNA Profiling: Circulating MicroRNAs as Noninvasive Cancer Biomarkers in Breast Cancer.

This report describes technologies to identify and quantify microRNAs (miRNAs) as potential cancer biomarkers, using breast cancer as an example. Most breast cancer patients are not diagnosed until the disease has advanced to later stages, which decreases overall survival rates. Specific miRNAs are up- or downregulated in breast cancer patients at various stages, can be detected in plasma and serum, and have shown promising preliminary clinical sensitivity and specificity for early cancer diagnosis or staging. Nucleic acid testing methods to determine relative concentrations of selected miRNAs include reverse transcription, followed by quantitative PCR (RT-qPCR), microarrays, and next-generation sequencing (NGS). Of these methods, NGS is the most powerful approach for miRNA biomarker discovery, whereas RT-qPCR shows the most promise for eventual clinical diagnostic applications.

Ultrastructural study of the encystation and excystation processes in Naegleria sp.

An important aspect of the biology of Naegleria sp. is the differentiation processes that occur during encystation and excystation. We studied these using both fluorescence and transmission electron microscopy techniques. In the initial stages of encystation, the cisternae of the endoplasmic reticulum became densely filled with a fibrillar material. Vesicles with a similar content that appeared to be derived from the cisternae were also observed in close contact with the plasma membrane. As encystation progressed, the fibrillar material became localized on the surface of the amoeba. An irregular compaction was observed in some areas of the cyst wall, which contained thin extensions of the cyst wall fibrillar material. Completely formed cysts had two to three ostioles, each sealed by an operculum. The operculum contained two areas in which a differential compaction of the fibrillar structure was observed. When excystation was induced, small dense granules (DGs), which were in close contact with fibrillar material were observed in the cyst cytoplasm and in the peritrophic space. During excystation, the more compact component of the operculum moves to enable the pseudopod of the emerging trophozoite to penetrate the ostiole. Vacuoles containing a fibrillar material, probably derived from the cyst wall, were observed in the cytoplasm of the pseudopodia. Our results provide a platform for further studies using biochemical markers to investigate the origin of the cyst wall as well as the role of DGs during excystation in Naegleria.

Dolor neuropático en cáncer de mama gabapentina versus carbamazepina / Neuropatic pain in breast cancer, gabapentina vs carbamazepina

El dolor neuropático en cáncer de mama es por efecto de las lesiones y disfunción en el sistema nervioso. Se caracteriza por presencia de alodinia, disestesia, parestesia y paroxismos de dolor agudo. Se realizó un estudio prospectivo, aleatorizado, fase III para determinar la eficacia, en términos de respuesta clínica, del tratamiento con gabapentina comparada con carbamazepina en mujerescon cáncer de mama estadios I, II, III y IV, con dolor neuropático. Las pacientes eran aleatorizadas a recibir (brazo A) gabapentina dosis de 300 mg de inicio y cada tres días se aumentaba 300 mg (25 pacientes) el (brazo B) carbamazepina 200 mg (25 pacientes) hasta obtener respuesta completa o la mayor dosis establecida. Las tasas de respuesta global fue 63 por ciento en el brazo A y 25 por ciento en el brazo B (P=0,032). Respuesta completa 19 por ciento vs 6 por ciento en el brazo A y B respectivamente. Respuesta parcial 44 por ciento (brazo A) vs 19 por ciento (brazo B). Enfermedad estable 31 por ciento vs 38 por ciento en el brazo A y brazo B respectivamente, progresión de enfermedad 6 por ciento (brazo A) y 38 por ciento (brazo B). Con toxicidades similares en ambos grupos. El esquema de tratamiento con gabapentina es más eficaz y bien tolerado que el de carbazepina, en pacientes con dolor neuropático y cáncer de mama.

Ultrastructure of cyst differentiation in parasitic protozoa.

Cysts represent a phase in the life cycle of biphasic parasitic protozoa that allow them to survive under adverse environmental conditions. Two events are required for the morphological differentiation from trophozoite to cyst and from cyst to trophozoite: the encystation and excystation processes. In this paper, we present a review of the ultrastructure of the encystation and excystation processes in Entamoeba invadens, Acanthamoeba castellanii, and Giardia lamblia. The comparative electron microscopical observations of these events here reported provide a morphological background to better understand recent advances in the biochemistry and molecular biology of the differentiation phenomena in these microorganisms.