Relationship between tumor-associated immune infiltrate and p16 staining over clinicopathological features in acral lentiginous melanoma.

PURPOSE: This study aims to evaluate the association between composition of tumor-infiltrating lymphocytes (TIL) and expression of p16 in acral lentiginous melanoma (ALM), and their impact on prognosis. MATERIALS AND METHODS: A cohort of 148 surgical pathology specimens of ALM was studied. TIL were evaluated by immunohistochemical detection of CD3 and CD8, along with CD20, CD4, CD68, and CD163 in a subset of 43 cases. p16 protein expression was also investigated in all the cases. RESULTS: The median age was 66 years, median Breslow thickness was 6.0 mm, grade III TIL was found in 28.4% and lymph nodes were involved in 54.2%. Breslow thickness (p < 0.001), stage I-II (p < 0.001), negative lymph nodes (p < 0.001) and < 10% p16 (p = 0.01) were associated with longer survival. Grade III of TIL was associated with thinner Breslow thickness (p = 0.008) and lower mitosis (p = 0.047). A higher density of CD3 TIL was associated with male gender (p = 0.008), thinner Breslow thickness (p = 0.047), negative lymph node (p = 0.031), early stage (p = 0.046), and p16 nuclear expression of > 10% (p = 0.045). Higher CD8 TIL was associated with > p16 (p = 0.03). Survival analysis found that longer survival had a trend to be associated with high TIL (p = 0.090). Levels of CD3+ and CD8+ cells were correlated with those of CD4+, CD20+, CD68+ and CD163+ immune cells. CONCLUSIONS: Higher levels of TIL tend to be associated with better overall survival in ALM. Loss of expression of p16 is associated with lower levels of CD3+ and CD8+ TIL, indicating a probable relationship between p16 and TIL immune response in ALM .

Tumor infiltrating lymphocytes in acral lentiginous melanoma: a study of a large cohort of cases from Latin America.

PURPOSE: Acral lentiginous melanoma (ALM) is a poor prognosis subtype and is the most prevalent in non-Caucasian populations. The presence of tumor infiltrating lymphocytes (TILs) has been associated with poor prognosis in melanoma. A large cohort of ALM cases was studied to determine status of TIL and its association with outcome. METHODS: All patients with cutaneous melanoma presenting from 2005 to 2012 at Instituto Nacional de Enfermedades Neoplasicas in Peru were retrospectively identified. Clinicopathological information was obtained from the medical charts. A prospective evaluation of TIL was performed. Analysis of association between ALM and clinicopathological features including TIL as well as survival analysis compared the outcome of ALM to whole group and extremity NALM was performed. RESULTS: 537 ALM from a total of 824 cutaneous melanoma cases were studied. Older age (p = 0.022), higher Breslow (p = 0.008) and ulceration (p < 0.001) were found to be more frequent in ALM. Acral had worse overall survival (OS) compared with the whole group (p = 0.04). Clinical stage (CS) I-II patients had a median OS of 5.3 (95% CI 4.3-6.2) for ALM and 9.2 (95% CI 5.0-7.0) for extremity NALM (p = 0.016). Grade 0 (absence of TIL), I, II and III were found in 7.5, 34.5, 32.1, and 25.9%, respectively. Lower TIL grade was associated with larger tumor size (p = 0.003), higher Breslow (p = 0.001), higher Clark level (p = 0.007), higher CS (p = 0.002), extremity location (p = 0.048), histological subtype ALM (p = 0.024) and better OS (p = 0.001). CONCLUSIONS: ALM is highly prevalent in Peru and carries poor outcome. Lower TIL levels were associated with poor outcome and ALM.

Sleep-related disorders in Latin-American children with atopic dermatitis: A case control study.

BACKGROUND: Atopic dermatitis (AD) has been associated with impairment of sleep. The aim of this study was to evaluate sleep disorders in AD Latin-American children (4-10 years) from nine countries, and in normal controls (C). METHODS: Parents from 454 C and 340 AD children from referral clinics answered the Children Sleep Habits Questionnaire (CSHQ), a one-week retrospective 33 questions survey under seven items (bedtime resistance, sleep duration, sleep anxiety, night awakening, parasomnias, sleep-disordered breathing and daytime sleepiness). Total CSHQ score and items were analysed in both C and AD groups. Spearman's correlation coefficient between SCORAD (Scoring atopic dermatitis), all subscales and total CSHQ were also obtained. RESULTS: C and AD groups were similar regarding age, however, significantly higher values for total CSHQ (62.2±16.1 vs 53.3±12.7, respectively) and items were observed among AD children in comparison to C, and they were higher among those with moderate (54.8%) or severe (4.3%) AD. Except for sleep duration (r=-0.02, p=0.698), there was a significant Spearman's correlation index for bedtime resistance (0.24, p<0.0001), sleep anxiety (0.29, p<0.0001), night awakening (0.36, p<0.0001), parasomnias (0.54, p<0.0001), sleep-disordered breathing (0.42, p<0.0001), daytime sleepiness (0.26, p<0.0001) and total CSHQ (0.46, p<0.0001). AD patients had significantly higher elevated body mass index. CONCLUSION: Latin-American children with AD have sleep disorders despite treatment, and those with moderate to severe forms had marked changes in CSHQ.

Sleep disorders in Latin-American children with asthma and/or allergic rhinitis and normal controls.

BACKGROUND: Asthma and/or allergic rhinitis have been associated with sleep disorders. The aim of this study was to evaluate sleep disorders in Latin-American children (4-10 years) from nine countries, with persistent asthma (A) and/or allergic rhinitis (AR) and in normal controls (C). METHODS: Parents from 454 C children and 700 A and/or AR children followed up in allergy reference clinics completed the Children's Sleep Habits Questionnaire (CSHQ) which is a retrospective one-week questionnaire composed of 33 questions composed of seven subscales (bedtime resistance, sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing and daytime sleepiness). The total scale of CSHQ and the subscales were compared between groups C and A+AR, A (n=285) vs. AR (n=390), and between controlled A (CA, n=103) vs. partially controlled/uncontrolled A (UA, n=182). RESULTS: The comparison between C and A+AR showed no significant differences in age (6.7 years vs. 7.0 years, respectively), mean Body Mass Index and total scale of CSHQ (53.3 vs. 63.2, respectively) and the subscales were significantly higher in the A+AR group. Comparison between groups A and AR, except for sleep anxiety, showed significantly higher values for CSHQ total scale (66.9 vs. 61.0, respectively) and subscales for group A. The UA group showed significantly higher values for total CSHQ scale and subscales in comparison to CA (71.1 vs. 59.4, respectively). CONCLUSIONS: Latin-American children with asthma and/or allergic rhinitis showed sleep disorders identified by the CSHQ when compared to normal controls. Despite being treated, asthma causes sleep impairment, especially when uncontrolled.

Biological parameters of interbreeding subspecies of Meccus phyllosomus (Hemiptera: Reduviidae: Triatominae) in western Mexico.

Understanding the biological parameters of some triatomine subspecies of Meccus phyllosomus (Burmeister) is a crucial first step in estimating the epidemiological importance of this group. Biological parameters related to egg eclosion, egg-to-adult development time, number of blood meals to moult, percentage of females at the end of the cycle, number of laid eggs, and the accumulative mortality for each instar of three M. phyllosomus subspecies [Meccus phyllosomus pallidipennis (Stål), Meccus phyllosomus longipennis (Usinger), and Meccus phyllosomus picturatus (Usinger)] as well as their laboratory hybrids were evaluated and compared. No significant differences (P > 0.05) were recorded among the experimental hybrids (M. p. longipennis × M. p. pallidipennis, M. p. longipennis × M. p. picturatus, M. p. pallidipennis × M. p. picturatus) and reciprocal cohorts. In five of the six studied parameters (egg eclosion, egg-to-adult development time, number of blood meals to moult, number of laid eggs and accumulative mortality), with the exception of the non-significant percentage of females obtained among all the studied cohorts, at least one of the parental cohorts in each set of crosses exhibited better fitness results than by those of their hybrid descendants. The lack of hybrid fitness in our study indicates the maintenance of reproductive isolation of parental genotypes. Moreover, the results lead us to propose that an incipient speciation process by distance is currently developing among the three studied subspecies, increasing the differences between them that modify the transmission efficiency of Trypanosoma cruzi to human beings in Mexico.

Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Peru.

The prevalence of BRCA1 and BRCA2 mutations among breast cancer patients in Peru has not yet been explored. We enrolled 266 women with breast cancer from a National cancer hospital in Lima, Peru, unselected for age or family history. DNA was screened with a panel of 114 recurrent Hispanic BRCA mutations (HISPANEL). Among the 266 cases, 13 deleterious mutations were identified (11 in BRCA1 and 2 in BRCA2), representing 5% of the total. The average age of breast cancer in the mutation-positive cases was 44 years. BRCA1 185delAG represented 7 of 11 mutations in BRCA1. Other mutations detected in BRCA1 included: two 2080delA, one 943ins10, and one 3878delTA. The BRCA2 3036del4 mutation was seen in two patients. Given the relatively low cost of the HISPANEL test, one should consider offering this test to all Peruvian women with breast or ovarian cancer.

[Efficacy of nifurtimox for the treatment of chronic Chagas disease]. / Eficacia de nifurtimox para el tratamiento de pacientes con enfermedad de Chagas crónica.

BACKGROUND: Most Chagas patients belong to the chronic indeterminate stage, in which pharmacological treatment has an inconclusive outcome. OBJECTIVE: To evaluate the efficacy of nifurtimox treatment in chronic asymptomatic Trypanosoma cruzi infection. METHODS: We performed a systematic review and meta-analysis of electronically published literature, with no language, type of study, age or gender restrictions, until September 2010. Studies of chronic asymptomatic Chagas disease patients treated exclusively with nifurtimox were included in the analysis. Treatment efficacy was evaluated using parasitological or serological parameters. RESULTS: Of 463 identified studies, 7 were finally selected: 6 observational studies and 1 randomized clinical trial; 4 of the studies were in adults, 3 in children < 14 years. In 6 studies, outcomes were defined by serological techniques. Summary estimate (log odds) was 0.37 (CI9 -1.32 - 2.07). CONCLUSIONS: The analyzed studies gave discordant results. Those might be explained by differences in the populations studied, follow-up periods, diagnostic techniques, and sample size. More studies are necessary to obtain conclusive results about treatment efficacy of nifurtimox in this clinical phase of T. cruzi infection.

Eficacia de nifurtimox para el tratamiento de pacientes con enfermedad de Chagas crónica / Efficacy of nifurtimox for the treatment of chronic Chagas disease

Background: Most Chagas patients belong to the chronic indeterminate stage, in which pharmacological treatment has an inconclusive outcome. Objective: To evaluate the efficacy of nifurtimox treatment in chronic asymptomatic Trypanosoma cruzi infection. Methods: We performed a systematic review and meta-analysis of electronically published literature, with no language, type of study, age or gender restrictions, until September 2010. Studies of chronic asymptomatic Chagas disease patients treated exclusively with nifurtimox were included in the analysis. Treatment efficacy was evaluated using parasitological or serological parameters. Results: Of 463 identified studies, 7 were finally selected: 6 observational studies and 1 randomized clinical trial; 4 of the studies were in adults, 3 in children < 14 years. In 6 studies, outcomes were defined by serological techniques. Summary estimate (log odds) was 0.37 (CI9 -1.32 - 2.07). Conclusions: The analyzed studies gave discordant results. Those might be explained by differences in the populations studied, follow-up periods, diagnostic techniques, and sample size. More studies are necessary to obtain conclusive results about treatment efficacy of nifurtimox in this clinical phase of T. cruzi infection.

Introducción: La mayoría de los pacientes con enfermedad de Chagas se encuentran en fase crónica indeterminada donde los resultados de tratamiento farmacológico no han sido concluyentes. Objetivo: Evaluar la evidencia que apoya la eicacia del tratamiento con nifurtimox en la infección crónica por Trypanosoma cruzi asintomática. Método: Revisión sistemática y meta-análisis de literatura publicada en forma electrónica, sin restricción de lenguaje, tipo de estudio, edad y género, hasta septiembre de 2010. Se incluyeron estudios de pacientes con enfermedad de Chagas crónica asintomáticos que recibieron tratamiento exclusivo con nifurtimox. La eicacia del tratamiento fue evaluada mediante métodos parasitológicos o serológicos. Resultados: Se identiicaron 463 estudios primarios seleccionando inalmente siete: seis observacionales y un ensayo clínico randomizado; cuatro en pacientes adultos y tres en niños bajo14 años de edad. En seis estudios los resultados se midieron mediantes técnicas serológicas. La medida resumen (log de la chance) fue de 0,37 (IC95% -1,32 -2,07). Conclusiones: Los resultados son discordantes. La incertidumbre se maniiesta por las diferencias en las poblaciones estudiadas, periodos de seguimiento, técnicas diagnósticas y tamaño de las muestras. Es necesario realizar nuevos estudios que consideren las fuentes de incertidumbre para obtener resultados concluyentes sobre la eicacia del nifurtimox en esta fase clínica de la infección por T. cruzi.

Helicobacter pylori y lesiones endoscópicas e histológicas en mucosa gástrica de pacientes de 50 años y más / Helicobacter pylori and the endoscopic and histological lesions in the gastric mucosa of patients aged 50 and over

Mundialmente es aceptado que la infección por Helicobacter pylori se incrementa con la edad y alcanza niveles entre 40 y 60 por ciento en sujetos asintomáticos y 70 por ciento en pacientes sintomáticos mayores de 50 años con enfermedades gastroduodenales. Teniendo en cuenta la relación entre la infección por Helicobacter pylori y las enfermedades gastroduodenales se cifran prevalencias e incidencias en aumento sostenido con la edad (50-70 por ciento en mayores de 50 años) y se considera el significado aumento de la población cubana por encima de esa edad. Se realizó un estudio prospectivo, descriptivo en el Instituto de Gastroenterología, para conocer la frecuencia de este microorganismo, así como la presencia de lesiones en la mucosa gástrica en pacientes de 50 y más años de edad. Se concluyó que el 69,6 por ciento de los pacientes tuvieron resultados positivos al Helicobacter pylori por test de ureasa; de los 132 fragmentos de muestras tomados para biopsias de la mucosa gástrica, el 37,8 por ciento fueron positivas para Helicobacter pylori, de ellas, el 25,7 por ciento se localizó en la región antral. Se realizaron 68 diagnósticos endoscópicos en los pacientes con Helicobacter pylori positivos por test de ureasa; 64,7 por ciento correspondió a gastritis crónica agudizada al nivel antral, seguido en orden de frecuencia por pangastritis, gastritis crónica agudizada al nivel del cuerpo, úlcera gástrica y úlcera duodenal. No se presentó lesión endoscópica de aspecto maligno en ningún paciente. Al estudiar la densidad de colonización de Helicobacter pylori en los 84 diagnósticos histológicos realizados, 69,0 por ciento presentó densidad ligera; 29,9 por ciento, moderada y 1,1 por ciento, severa. Se observó una tendencia hacia la densidad de colonización ligera a medida que progresaba la lesión histológica...

It is accepted all over the world that Helicobacter pylori infection increases with age and reaches levels between 40 and 60 percent in asymptomatic individuals, and of 70 percent in symptomatic patients over 50 with gastroduodenal diseases. Taking into account the relation existing between Helicobacter pylori infection and the gastroduodenal diseases, prevalences and incidences showing a sustained increase with age (50-70 percent in patients over 50) are ciphered, and the significant growth of the Cuban population above this age is considered. A prospective and descriptive study was undertaken at the Institute of Gastroenterology to know the frequency of this microorganism, as well as the presence of lesions in the gastric mucosa in patients aged 50 and over. It was concluded that 69.6 percent of the patients had positive results to Helicobacter pylori in the urease test. Of the 132 fragments of samples taken for biopsies of the gastric mucosa, 37.8 percent yielded positive to Helicobacter pylori, of them, 25.7 percent were located in the antral region. 68 endoscopic diagnoses were made in those patients positive to Helicobacter pylori by urease test, 64.7 percent corresponded to more acute gastritis at the antral level; followed in frequency by pangastritis, more serious chronic gastritis at the body level, gastric ulcer and duodenal ulcer. No endoscopic lesion of malignant aspect was observed. On studying the colonization density of Helicobacter pylori in 84 histological diagnoses made, 69.0 percent presented mild density; 29.9 percent, moderate; and 1.1 percent, severe. It was observed a tendency towards the colonization density as the histological lesion progressed. It was suggested to continue the study with more patients to characterize the behavior of the infection in patients aged 50 and over in order to take preventive measures to eradicate the bacteria and to improve the quality of life.

Molecular multivalent electrolytes: microstructure and screening lengths.

We study small rod-like molecular electrolytes solutions with their corresponding atomic counterions. The asymptotic length scales (decay length and wavelength) of the structural correlations are analyzed using the formalism of the dressed interaction site theory (DIST). The correlation functions are determined using the reference interaction site model equation complemented with a mixed approach in which the hypernetted-chain closure is used for the repulsive interactions, and the mean spherical approximation is used for the attractive interactions. The results from this scheme are in good agreement with the Monte Carlo computer simulations reported here. The asymptotic properties of the correlation functions of this molecular system are compared against those corresponding to two related simple (atomic) electrolyte models. The main conclusion is that the molecular structure of the ions lowers by two orders of magnitude the concentration at which the transition from monotonic to oscillatory decay occurs.

[Teratology and epidemiology in the study of environmental teratogens]. / La teratología y la epidemiología en el estudio de los teratógenos ambientales.

The processes of cellular migration, cellular differentiation and cellular multiplication are studied, since these are the basic developmental processes upon which teratogenic agents act resulting in congenital malformations. We also carefully analyze the interactions between teratogen-embryo in order to establish adequate parameters for analysis of environmental teratogens, as well as experimental teratogenesis and epidemiology. Information on the pathogenesis of congenital malformations obtained from experimental teratology in an adequate biological model, can be extrapolated to the human. The etiology of congenital malformations resulting from environmental teratogens can only be elucidated through epidemiology, since there is species specificity. Such a study must fulfill the following prerequisites: diagnosis of the congenital malformation, ruling out genetic factors in the family tree and determination of the exact time of exposure to the possible teratogen during the pregnancy.

[Embryologic and anatomic considerations on normal and pathologic heart separation. II. Atrioventricular and interventricular septum]. / Consideraciones embriológicas y anatómicas sobre la septación cardiaca normal y patológica. II. Septum atrioventricular e interventricular.

The atrioventricular septum is defined and its anatomical features are described. This consists of two regions, a muscular and a membranous region. Isolated atrioventricular types of defect are described. The normal and the pathological embryogenesis of the atrioventricular septum are discussed. A definition of the interventricular septum is given and its anatomical features are described. This septum is divided into two regions, a membranous and muscular region. The muscular region is divided into three regions: inflow region or inlet, trabeculated region and outflow region or outlet. Interventricular defects are classified according to the septal regions in which they are located. The anatomical features which characterize each type of interventricular septal defect are established. A brief comment on the normal and pathological morphogenesis of the interventricular septum is made.

[Embryologic and anatomic considerations on the normal and pathologic formation of the cardiac septum. I. Interauricular septum]. / Consideraciones embriológicas y anatómicas sobre la septación cardiaca normal y patológica. I. Septum interauricular.

A brief presentation of the normal embryological development of the human interatrial septum is made. The anatomical expression of each of its embryological components is described. Our classification of interatrial septal defect is enriched by their more precise anatomical description and by making a more correct morphogenetic interpretation, based on new information obtained by means of experimental embryology. Emphasis is made that absence of the interatrial septum does not preclude the diagnosis of viscero-atrial situs.