A phase I trial of LXS196, a protein kinase C (PKC) inhibitor, for metastatic uveal melanoma.

BACKGROUND: Up to 50% of patients with uveal melanoma develop metastases (MUM) with a poor prognosis and median overall survival of approximately 1 year. METHODS: This phase I study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the oral protein kinase C inhibitor LXS196 in 68 patients with MUM (NCT02601378). Patients received LXS196 doses ranging from 100-1000 mg once daily (QD; n = 38) and 200-400 mg twice daily (BID; n = 30). RESULTS: First cycle dose-limiting toxicities (DLTs) were observed in 7/38 (18.4%) QD and 2/17 (11.8%) BID patients. Hypotension was the most common DLT, occurring at doses ≥500 mg/day, and manageable with LXS196 interruption and dose reduction. Median duration of exposure to LXS196 was 3.71 months (range: 1.81-15.28) for QD and 4.6 months (range: 0.33-58.32) for BID dosing. Clinical activity was observed in 6/66 (9.1%) evaluable patients achieving response (CR/PR), with a median duration of response of 10.15 months (range: 2.99-41.95); 45/66 had stable disease (SD) per RECIST v1.1. At 300 mg BID, the recommended dose for expansion, 2/18 (11.1%) evaluable patients achieved PR and 12/18 (66.7%) had SD. CONCLUSION: These results suggest manageable toxicity and encouraging clinical activity of single-agent LXS196 in patients with MUM.

Single-agent anti-PD-1 or combined with ipilimumab in patients with mucosal melanoma: an international, retrospective, cohort study.

BACKGROUND: Mucosal melanoma (MM) is a rare melanoma subtype with distinct biology and poor prognosis. Data on the efficacy of immune checkpoint inhibitors (ICIs) are limited. We determined the efficacy of ICIs in MM, analyzed by primary site and ethnicity/race. PATIENTS AND METHODS: A retrospective cohort study from 25 cancer centers in Australia, Europe, USA and Asia was carried out. Patients with histologically confirmed MM were treated with anti-programmed cell death protein 1 (PD-1) ± ipilimumab. Primary endpoints were response rate (RR), progression-free survival (PFS), overall survival (OS) by primary site (naso-oral, urogenital, anorectal, other), ethnicity/race (Caucasian, Asian, Other) and treatment. Univariate and multivariate Cox proportional hazards model analyses were conducted. RESULTS: In total, 545 patients were included: 331 (63%) Caucasian, 176 (33%) Asian and 20 (4%) Other. Primary sites included 113 (21%) anorectal, 178 (32%) urogenital, 206 (38%) naso-oral and 45 (8%) other. Three hundred and forty-eight (64%) patients received anti-PD-1 and 197 (36%) anti-PD-1/ipilimumab. RR, PFS and OS did not differ by primary site, ethnicity/race or treatment. RR for naso-oral was numerically higher for anti-PD-1/ipilimumab [40%, 95% confidence interval (CI) 29% to 54%] compared with anti-PD-1 (29%, 95% CI 21% to 37%). Thirty-five percent of patients who initially responded progressed. The median duration of response (mDoR) was 26 months (95% CI 18 months-not reached). Factors associated with short PFS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3 (P < 0.01), lactate dehydrogenase (LDH) more than the upper limit of normal (ULN) (P = 0.01), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). Factors associated with short OS were ECOG PS ≥1 (P < 0.01), LDH >ULN (P = 0.03), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). CONCLUSIONS: MM has poor prognosis. Treatment efficacy of anti-PD-1 ± ipilimumab was similar and did not differ by ethnicity/race. Naso-oral primaries had numerically higher response to anti-PD-1/ipilimumab, without difference in survival. The addition of ipilimumab did not show greater benefit over anti-PD-1 for other primary sites. In responders, mDoR was short and acquired resistance was common. Other factors, including site and number of metastases, were associated with survival.

Dual checkpoint inhibitor-associated eosinophilic enteritis.

BACKGROUND: Eosinophilia has been reported as a rare, new biological effect of immune checkpoint inhibition that may be associated with improved treatment response and the development of immune-related adverse events. CASE PRESENTATION: We report a case of dual checkpoint inhibitor-associated hypereosinophilia and eosinophilic enteritis in a patient with advanced cutaneous melanoma. Rapid resolution of peripheral eosinophilia and associated symptoms was achieved with steroids alone. CONCLUSIONS: Immune checkpoint inhibition can trigger inflammation in virtually any organ in the body, leading to diverse clinical manifestations. To our knowledge, this is the first case report of eosinophilic enteritis due to ipilimumab plus nivolumab.

Meta-analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an international rare cancers initiative (IRCI) ocular melanoma study.

BACKGROUND: Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) and overall survival (OS), we carried out a meta-analysis using individual patient level trial data. METHODS: Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated. RESULTS: OS data were available for 912 patients. The median PFS was 3.3 months (95% CI 2.9-3.6) and 6-month PFS rate was 27% (95% CI 24-30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3 cm versus <3 cm) to be substantially associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH and elevated ALP were substantially associated with shorter PFS. The most substantial factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2 months (95% CI 9.5-11.0) and 1 year OS was 43% (95% CI 40-47). The most substantial prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS. CONCLUSION: Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.

Efficacy and safety of nilotinib in patients with KIT-mutated metastatic or inoperable melanoma: final results from the global, single-arm, phase II TEAM trial.

BACKGROUND: The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT-mutated advanced melanoma without prior KIT inhibitor treatment. PATIENTS AND METHODS: Forty-two patients with KIT-mutated advanced melanoma were enrolled and treated with nilotinib 400 mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients; the design was amended to a single-arm trial due to an observed low number of KIT-mutated melanomas. Thirteen patients were randomized to DTIC before the protocol amendment removing this study arm. The primary endpoint was objective response rate (ORR), determined according to Response Evaluation Criteria In Solid Tumors. RESULTS: ORR was 26.2% (n = 11/42; 95% CI, 13.9%-42.0%), sufficient to reject the null hypothesis (ORR ≤10%). All observed responses were partial responses (PRs; median response duration, 7.1 months). Twenty patients (47.6%) had stable disease and 10 (23.8%) had progressive disease; 1 (2.4%) response was unknown. Ten of the 11 responding patients had exon 11 mutations, four with an L576P mutation. The median progression-free survival and overall survival were 4.2 and 18.0 months, respectively. Three of the 13 patients on DTIC achieved a PR, and another patient had a PR following switch to nilotinib. CONCLUSION: Nilotinib activity in patients with advanced KIT-mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential activity, although the low patient number limits interpretation. Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01028222.

Proinflammatory environment and role of TNF-α in endometrial function of obese women having polycystic ovarian syndrome.

BACKGROUND/OBJECTIVES: A high percentage of women having polycystic ovarian syndrome (PCOS) exhibit hyperinsulinemia and obesity. Transforming necrosis factor-α (TNF-α) is an adipokine that increases in obesity and negatively affects insulin action in several tissues, including the endometrium. In fact, it has been reported that insulin signaling is altered in the endometrium of PCOS women, affecting its reproductive function. The aim of this study was to determine the proinflammatory environment and TNF-α signaling in endometrium from obese women with PCOS, and also to evaluate the effect of TNF-α on endometrial cell energy homeostasis. METHODS: Serum and endometrial tissues were obtained from four study groups: normal-weight, normal-weight-PCOS, obese and obese-PCOS (hyperandrogenemia/hyperinsulinemia) (n=7 per group). Serum TNF-α level was assayed by enzyme-linked immunosorbent assay (ELISA); endometrial TNF-α level and its receptors (TNFR1/TNFR2) as well as nuclear factor (NF)-κB content were determined by immunohistochemistry. Finally, we evaluated TNF-α effect on glucose uptake in cultured human endometrial stromal cells (T-HESC) treated or not with testosterone/insulin resembling partially the PCOS condition. RESULTS: TNF-α plasma levels were similar between groups, whereas cytokine levels and macrophage number increased in endometrium from obese-PCOS women (P<0.001). Both receptor types were higher in obese vs normal-weight women, particularly TNFR2 content in the obese-PCOS group (P<0.001). Furthermore, an increased NF-κB nuclear content in endometrium from obese-PCOS was observed (P<0.001). Finally, TNF-α treatment of T-HESC cultures exhibited a decrease of glucose uptake (P<0.05), although similar to cells treated with testosterone or testosterone/insulin/TNF-α. CONCLUSIONS: These results suggest that the PCOS condition induces an inflammatory state exacerbated when obesity is present, where a higher TNF-α signaling is observed, all of which could affect glucose uptake in the tissue and may cause fertility failures in these women.

Corrigendum to "Sarcoma Immunotherapy: Past Approaches and Future Directions".

[This corrects the article DOI: 10.1155/2014/391967.].

Association between Abnormal Electrocardiogram and Less Complex Heart Rate Variability Estimated by the Correlation Dimension / Asociación entre Electrocardiograma Anormal y Menor Complejidad de la Variabilidad de la Frecuencia Cardiaca Estimada Mediante la Dimensión de Correlación

Objective: To compare the correlation dimension (CD) of heart rate variability (HRV) in adults with and without abnormal electrocardiogram (ECG). Methods: A 24-hr Holter and a standard ECG were recorded from 100 university workers. After exclusion of 10 recordings with more than 5% of false RR intervals, a total of 90 subjects (age 46.2±8.7 years old, 45 were women) were included in the study. Two cardiologists classified 29 standard ECG as abnormal. CD was calculated from HRV time-series of 10,000 beats in the morning (from 11am), afternoon (from 5pm) and night (from 2am). Demographical characteristics were compared by ANOVA (considering ECG diagnosis and sex as independent factors) or by Fisher's exact test. Mean CD values were compared by analysis of variance considering as independent factors the ECG diagnosis, sex and time of day. Results: All demographical characteristics were similar except for a higher proportion of males with abnormal ECG (69%) than with normal ECG (41%). CD was not different with respect to the time of day, but it was higher in subjects with normal ECG (10.86 ± 2.41) than those with abnormal ECG (10.20 ± 2.48), and it was also higher in females than males: 11.04 ± 2.14 versus 10.63 ± 2.71 (normal ECG group), 10.84 ± 2.41 versus 9.92 ± 2.44 (abnormal ECG group). Conclusion: The finding of abnormal ECG is associated with HRV decreased complexity in adults.

Objetivo: Comparar la dimensión de correlación (DC) de la variabilidad de la frecuencia cardiaca (VFC) entre adultos con electrocardiograma (ECG) normal y anormal. Métodos: Se registró un Holter de 24 horas y un electrocardiograma (ECG) estándar de 100 trabajadores universitarios. Después de la exclusión de 10 registros con más de 5% de intervalos RR falsos, se incluyeron en el estudio a 90 sujetos (edad 46.2±8.7 años, 45 mujeres). Dos cardiólogos clasificaron 29 ECG estándar como anormales. La DC se calculó en series de tiempo de VFC de 10,000 latidos en la mañana (desde las 11:00), tarde (desde las 17:00) y noche (desde las 2:00). Las características demográficas fueron comparadas mediante análisis de varianza (considerando diagnóstico de ECG y sexo como factores independientes) o con prueba exacta de Fisher. Los valores promedio de DC fueron comparados con análisis de varianza considerando como factores independientes el diagnóstico de ECG, sexo y hora del día. Resultados: Las características demográficas fueron similares excepto por mayor proporción de hombres con ECG anormal (69%) que normal (41%). La DC no fue diferente con respecto a la hora del día, pero fue mayor en sujetos con ECG normal (10.86 ± 2.41) que con ECG anormal (10.20 ± 2.48), y también fue mayor en mujeres que en hombres: 11.04 ± 2.14 vs 10.63 ± 2.71 (grupo de ECG normal), 10.84 ± 2.41 vs 9.92 ± 2.44 (grupo de ECG anormal). Conclusión: El hallazgo de ECG anormal en adultos está asociado con menor complejidad de la VFC.

Sarcoma immunotherapy: past approaches and future directions.

Sarcomas are heterogeneous malignant tumors of mesenchymal origin characterized by more than 100 distinct subtypes. Unfortunately, 25-50% of patients treated with initial curative intent will develop metastatic disease. In the metastatic setting, chemotherapy rarely leads to complete and durable responses; therefore, there is a dire need for more effective therapies. Exploring immunotherapeutic strategies may be warranted. In the past, agents that stimulate the immune system such as interferon and interleukin-2 have been explored and there has been evidence of some clinical activity in selected patients. In addition, many cancer vaccines have been explored with suggestion of benefit in some patients. Building on the advancements made in other solid tumors as well as a better understanding of cancer immunology provides hope for the development of new and exciting therapies in the treatment of sarcoma. There remains promise with immunologic checkpoint blockade antibodies. Further, building on the success of autologous cell transfer in hematologic malignancies, designing chimeric antigen receptors that target antigens that are over-expressed in sarcoma provides a great deal of optimism. Exploring these avenues has the potential to make immunotherapy a real therapeutic option in this orphan disease.

High-risk features in radiation-associated breast angiosarcomas.

BACKGROUND: Radiation-associated breast angiosarcoma (RT-AS) is an uncommon malignancy with an incidence of less than 1 % of all soft tissue sarcomas. The overall prognosis is quite dismal with high rates of recurrences and poor overall survival. There is an obvious paucity of data regarding clinical outcomes of patients with breast RT-AS. METHODS: We identified all patients with RT-AS treated at the Memorial Sloan-Kettering Cancer Center between 1982-2011 and collected their correlative clinical information. RESULTS: We identified 79 women with RT-AS with a median age of 68 (range 36-87). The median interval between radiation and development of RT-AS was 7 years (range 3-19). The median time to local and distant recurrence was 1.29 years (95 % CI 0.72-NA) and 2.48 years (95 % CI 1.29-NA), respectively. The median disease-specific survival was 2.97 years (95 % CI 2.21-NA). Independent predictors of worse disease-specific survival included age 68 years (HR 3.11, 95 % CI 1.20-8.08, P=0.020) and deep tumors (HR 3.23, 95 % CI 1.02-10.21, P=0.046.) CONCLUSION: RT-AS has high local/distant recurrence rates, limited duration on standard chemotherapy and poor disease-specific survival.

Managing obesity in primary care practice: an overview with perspective from the POWER-UP study.

Primary care practitioners (PCPs) have been encouraged to screen all adults for obesity and to offer behavioral weight loss counseling to the affected individuals. However, there is limited research and guidance on how to provide such intervention in primary care settings. This led the National Heart, Lung and Blood Institute in 2005 to issue a request for applications to investigate the management of obesity in routine clinical care. Three institutions were funded under a cooperative agreement to undertake the practice-based opportunities for weight reduction (POWER) trials. The present article reviews selected randomized controlled trials, published before the initiation of POWER, and then provides a detailed overview of the rationale, methods and results of the POWER trial conducted at the University of Pennsylvania (POWER-UP). POWER-UP's findings are briefly compared with those from the two other POWER trials, conducted at Johns Hopkins University and Harvard University/Washington University. The methods of delivering behavioral weight loss counseling differed markedly across the three trials, as captured by an algorithm presented in the article. Delivery methods ranged from having medical assistants and PCPs from the practices provide counseling to using a commercially available call center, coordinated with an interactive website. Evaluation of the efficacy of primary care-based weight loss interventions must be considered in light of costs, as discussed in relation to the recent treatment model proposed by the Centers for Medicare and Medicaid Services.

Ipilimumab for metastatic melanoma.

Malignant melanoma is currently the fifth most common cancer in American men and the seventh most common in American women. Despite the advances made for early disease, the prognosis for metastatic melanoma is dismal, with an overall 5-year mortality rate of 90%. It is estimated that 8,000 Americans will die of melanoma in 2012. Recent advances in the understanding of the complex cellular interactions regulating cancer immunity have led to new strategies in the development of cancer immunotherapy. The discovery of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a negative regulator of immune activity, has led to the development of a monoclonal antibody, ipilimumab, that can abrogate immune suppression. Ipilimumab is the first immunotherapy approved by the FDA for patients with advanced melanoma based on the overall survival benefit in a phase III setting. It represents a paradigm shift in melanoma management with its success promoting the evaluation of monoclonal antibodies targeted against a number of other regulatory checkpoints in patients with advanced melanoma.

Hernia traumática de pared abdominal secundaria a atrición por tronco de árbol / Traumatic abdominal wall hernia: case report

We report a 34 years old male that while working in forest activities, suffered a blunt trauma caused by the trunk of a tree. On abdominal examination, a bulging on the right upper quadrant with ecchymoses was noted. And abdominal CAT scan showed a great defect of right oblique and transverse abdominis muscles with herniation of the ascending colon. The patient was operated, finding a hemoperitoneum. The abdominal cavity was washed thoroughly and the wall defect was covered with a mesh. The patient had an uneventful postoperative recovery and was discharged nine days later.

Las hernias traumáticas de pared abdominal (HTPA) son una patología poco frecuente. Se definen como la rotura musculofascial causada por un traumatismo directo, sin penetración de la piel ni evidencia de hernia previa en el sitio de la lesión. El 78 por ciento son causadas por accidentes viales y en menor frecuencia por patadas de animales, caídas de altura, traumas deportivos, utensilios profesionales y aplastamientos. Presentamos el caso de un paciente masculino de 34 años derivado al Servicio de Urgencia del Hospital de Chillan por atrición toracoabdominal derecha, en faena forestal, cuyo estudio tomográfico revela gran defecto de músculos oblicuos y transversos derechos con herniación de colon ascendente hacia la pared abdominal.

Phase II trial of neoadjuvant temozolomide in resectable melanoma patients.

BACKGROUND: We treated melanoma patients with temozolomide (TMZ) in the neoadjuvant setting and collected cryopreserved tumor samples before and after treatment. The primary objective was to determine whether the response proportion was higher than previously reported in widely metastatic patients. A secondary objective was to test the feasibility of obtaining adequate tissue before and after treatment for genetic testing. MATERIALS AND METHODS: Chemotherapy-naive melanoma patients who were candidates for surgical resection were eligible. TMZ was administered orally at 75 mg/m(2)/day for 6 weeks of every 8-week cycle. Cycles were repeated until complete response (CR), progression, or stable disease (SD) for two cycles. RESULTS: Of 19 assessable patients, 2 had CRs and 1 had partial response. Four patients had SD; 12 progressed. Tumor O-6-methylguanine-DNA methyltransferase (MGMT) promoter was unmethylated in all nine patients analyzed including from the two CR patients. Pretreatment tumor microarray results were obtained in 16 of 19 patients. CONCLUSIONS: The response proportion to TMZ in the neoadjuvant setting was 16%, not different than in the metastatic setting. Responses were seen even in tumors with a methylated MGMT promoter. Pretreatment cryopreserved tumor adequate for microarray analysis could be obtained in most, but not all, patients. Post-treatment tumor was unavailable in complete responders.

Safety, tolerability, pharmacokinetics and pharmacodynamics of the oral cyclin-dependent kinase inhibitor AZD5438 when administered at intermittent and continuous dosing schedules in patients with advanced solid tumours.

BACKGROUND: AZD5438 is an orally bioavailable inhibitor of cyclin E-cdk2, cyclin A-cdk2 and cyclin B-cdk1 complexes. Three phase I studies assessed the clinical safety, tolerability, pharmacokinetics and pharmacodynamics of AZD5438 when administered in different dosing schedules. PATIENTS AND METHODS: AZD5438 was administered four times daily, once every 7 days (study 1), for 14 consecutive days followed by 7 days of rest (study 2), or continuously (study 3), to patients with advanced solid tumours. Dose escalation proceeded until the emergence of dose-limiting toxic effects. RESULTS: Sixty-four patients were included across the three studies (19, 17 and 28, respectively). Nausea and vomiting were the most common adverse events. When dosed continuously, 40 mg four times daily was considered intolerable, and due to safety issues, all studies were terminated prematurely. Consequently, no intolerable dose was identified during the weekly schedule. Pharmacokinetics demonstrated dose-proportional exposure, high interpatient variability and accumulation after multiple doses. Skin biopsies indicated reduced retinoblastoma protein phosphorylation at cdk2 phospho-sites; other pharmacodynamic assessments did not reveal consistent trends. CONCLUSIONS: AZD5438 was generally well tolerated in a weekly dosing schedule, but not in continuous schedules. The clinical development programme for AZD5438 was discontinued owing to tolerability and exposure data from these studies.

Estudio comparativo de la morbimortalidad del producto gestacional en mujeres embarazadas con preeclampsia modera o severa / Comparative study of morbimortality of gestational product in pregnant women with mild or severe preeclampsia

INTRODUCCION: La preeclampsia es una enfermedad exclusiva de la gestación humana, que afecta a la embarazada produciendo una disfunción vascular. OBJETIVO: Comparar la morbimortalidad del producto gestacional en mujeres embarazadas con preeclampsia (PE) moderada o severa. PACIENTES Y METODO: Estudio de tipo no experimental, descriptivo, por causa-efecto, de carácter retrospectivo. La población estudiada correspondió a toda paciente que sufrió PE, subclasificada en dos grupos; pacientes con PE moderada y pacientes con PE severa. El estudio se realizó en la Clínica Hospital del Profesor en el período comprendido entre junio del año 2007 y junio del año 2008. Se analizaron variables clínicas del recién nacido y de la embarazada. Los resultados obtenidos fueron analizados por medio de las pruebas de comparación de medias poblacionales y comparación de proporciones poblacionales. RESULTADOS: De un total de 1680 embarazos registrados en la Clínica Hospital del Profesor, 42 fueron diagnosticados con síndrome hipertensivo del embarazo (SHE), correspondiendo a un 2,5 por ciento. 28 (66 por ciento) correspondieron a PE moderada, 13 (32 por ciento) correspondieron a PE severa. El retardo del crecimiento intrauterino (RCIU) presentó diferencia significativa con un p< 0,05. El sufrimiento fetal agudo (SFA) y la mortalidad fetal, no presentaron diferencia significativa con un p> 0,05. CONCLUSION: Si bien las diferencias clínicas para el diagnóstico de preeclampsia moderada y severa son claras, las complicaciones que pueden traer al producto de la gestación no presentan diferencia, salvo al analizar el RCIU.

INTRODUCTION: Preeclampsia is an exclusive disease of human gestation, that affects pregnant women producing vascular dysfunction. AIM: Compare the morbid-mortality of the gestational product in pregnant women with mild or severe preeclampsia (PE). PATIENT AND METHODS: Retrospective, descriptive, non experimental, cause-effect study. The studied subjects were women that suffered with PE, sub-classified in two groups, mild PE patients and severe PE patients. The study was made in the “Clínica Hospital del Profesor” from June 2007 to June 2008. Different clinical parameters from the newborn and the pregnant were analyzed. The results were analyzed by the comparison of population and population ratio tests. RESULTS: From a total of 1680 pregnant women registred in the “Clínica Hospital del Profesor”, 42 were diagnosed pregnancy-induced hypertension / gestational hypertension, which represents 2.5 percent of all pregnancies. 28 (66 percent) represents to a moderate PE, 13(32 percent) represents to a severe PE. Intrauterine growth restriction presented a significant difference with an p< 0,05. The acute fetal suffering and fetal mortality didn’t have a significant difference with an p> 0,05. CONCLUSION: Although the clinical differences for the diagnose of mild and severe PE are clear, the complications that may ocurre to the product of the pregnancy don’t present a significant difference, except for the intrauterine growth restriction, that presented a significant difference with an alpha = 0,05.

Efectos producidos en la salud y el medio ambiente por el uso de agroquímicos: estudio preliminar en Huaricana, Provincia Murillo, La Paz / Effects produced in the health and the medium evironment by the use of agrochemical: preliminary study in Huaricana province Murillo of the peace

El uso de agroquímicos está muy extendido en las zonas agrícolas de Bolivia y se han detectado problemas de salud en agricultores de zonas rurales relacionadas con el uso intensivo de estas sustancias. Los efectos en la salud de los consumidores de alimentos con residuos de plaguicidas aún no han sido valorados ni tampoco el impacto en la biodiversidad. En Huaricana, Provincia Murillo del Departamento de La Paz, se evidenció el uso de plaguicidas como el paratión, metamidofós y dimetoato de manera sistemática y con total ausencia de criterios técnicos. El paratión, no obstante ser un plaguicida de venta prohibida según los organismos competentes, es de venta libre en los mercados y locales de expendio de agroquímicos. Se ha encontrado, una alta tasa de síntomas de intoxicación en la población agrícola estudiada, expresada en síntomas de origen nervioso central. Se encuentran datos sobre prevalencia de enfermedades respiratorias y gastrointestinales muy altos con relación a regiones agrícolas más pobres y de clima menos beningno, lo que podría señalar una menor capacidad inmunológica en los pobladores de Huaricana. Se descute la persistencia de estos compuestos en suelos como factor modificador de la biodiversidad edafológica

The effect of ethnicity and age on palatal size and shape: a study in a northern Chilean healthy population.

Race and ethnicity influence the form of the human craniofacial complex in varying ways. The aim of the present investigation was to quantify the effects of ethnicity (mestizos, Aymara, non-Aymara), age (adolescents and adults), and sex on the form (size and shape) of the hard palate in normal Native American individuals. From the dental casts of 51 individuals with a complete permanent dentition, the x, y, and z coordinates of several standardized palatal landmarks were obtained with a computerized 3-dimensional digitizer. Palatal landmarks were used to derive a mathematical equation for palatal shape in the frontal and sagittal planes. Palatal width and length, frontal and sagittal heights, sagittal slope, and deviation of the raphe from the midline were also calculated. In the Aymara subjects, there was no effect of sex on palatal size, but there was an effect on palatal shape independent of size, especially with respect to male growth. Indeed, female palates apparently did not change their shape between adolescence and adulthood, while male palates increased their posterior "height." Overall, the 3 ethnic groups appeared to possess similar palatal size, with small significant differences. In the adult individuals, ethnicity did not seem to influence palatal shape. In contrast, adolescent males showed differences: non-Aymara subjects had the "highest" palatal shape, Aymara the "lowest," and mestizos an intermediate position. In conclusion, ethnicity does not seem to be a factor of major variability of human hard palate morphology, at least in the present 3 northern Chilean groups, as already found for dental arch shape. Age probably has a larger effect, particularly in the posterior part of the palate, where the eruption of the second and third molars between adolescence and young adulthood may play a role. A further development of the present investigation may involve larger samples of individuals from different ethnic groups.

Dental arch size in healthy human permanent dentitions: ethnic differences as assessed by discriminant analysis.

Race and ethnicity variably influence the form of the human craniofacial complex. In the present study, the effects of ethnicity and sex on the global size of normal adult dental arches were analyzed. The dental arches of 47 northern Chilean mestizos (25 men, 22 women) and 95 northern Italian Caucasians (50 men, 45 women) were cast in stone. All subjects had a complete dentition in both arches. In all models the coordinates of dental cusp tips were digitized using an image analyzer. The center of gravity of each tooth was computed and arches were interpolated using a polynomial model (y = ax + bx2 + cx3 + dx4). In all arches, the intercanine, intermolar, and mid-intercanine to mid-intermolar distances were computed from the dental centers of gravity. These arch distances were entered in a linear discriminant function analysis. The polynomial model accurately interpolated data points in all instances, and most of the dental arch form was determined by the first and second degree coefficients. On average, Italian Caucasian arches were smaller than Chilean mestizo arches. Male mean distances were larger than female distances regardless of ethnic group or arch. The linear discriminant analysis performed between male and female arches within ethnic groups was significant only for both Italian Caucasian arches, but the percentage errors for the classification of a new individual were very high (about 30%). Conversely, Italian Caucasian arches could always be discriminated from Chilean mestizo arches of the same sex with a much smaller error.

Frecuencia de especificidades serológicas HLA en población boliviana / Frequency of especifidades serological HLA in Bolivian population

Se conoce por historia que la población boliviana es una mezcla de Amerindios y españoles, denominados mestizos. El presente estudio se realizó para determinar la distribución de las moléculas HLA en esta población. Una muestra de 119 individuos fué tipificada por serología para HLA. El análisis de las frecuencias de especificidades serológicas HLA y haplotípicas obtenidas, junto con el delta del desequilibrio de ligamiento, mostraron que, la distribución de los genes HLA en esta población provienen de Amerindios (p>0.1) en mayor proporción, asiáticos (p<0.01) y españoles caucasoides (p<0.001) en proporciones menores. Moléculas HLA características de población negroide no pudieron ser evidenciadas (p<0.0001). Nuestros resultados añaden evidencia a la hipótesis histórica de que con la llegada de españoles a América 500 añós atrás, la mezcla ha originado una población mestiza con características particulares. El reconocimiento de estos parámetros, podría permitir una mejor aplicación de la tecnología HLA en los campos de investigación básica, transplante de órganos, y medicina forense