Leucemia promielocítica aguda durante el embarazo: reporte de 17 casos de un país en desarrollo / Acute promyelocytic leukemia during pregnancy: report of 17 cases from a developing country

Resumen OBJETIVO: Recopilar casos atendidos en centros oncológicos de México y reportar los tratamientos exitosos, con respuestas completas y las complicaciones del embarazo. MATERIALES Y MÉTODOS: Estudio retrospectivo de serie de casos que incluyó a pacientes con leucemia promielocítica aguda asociada con el embarazo atendidas en diferentes hospitales de la zona metropolitana de la Ciudad de México entre 1999 y 2021. RESULTADOS: Se identificaron 17 pacientes con leucemia promielocítica aguda asociada con el embarazo, con mediana de edad de 23 años (14-40 años); 7 correspondieron a madres menores de 20 años. En relación con su entorno social 9 tenían baja escolaridad, 12 se dedicaban al hogar y 13 tenían una pareja al momento de la concepción. Por último, 11 eran originarias de una zona urbana. Las pacientes atendidas entre 1999-2010 se trataron con interferón plus citarabina (7 de 17) o mediante soporte transfusional y esteroide (2 de 17), en 8 de los 17 casos el tratamiento se inició con tretinoína en combinación con quimioterapia (daunorrubicina) como tratamiento de inducción. CONCLUSIONES: El tratamiento de pacientes embarazadas y con leucemia promielocítica aguda representa un reto debido al riesgo trombótico y hemorrágico. Si bien la adición de tretinoína ha modificado el pronóstico de las pacientes con esta leucemia, su indicación a las embarazadas sigue siendo motivo de controversia, sobre todo por el riesgo de teratogenicidad.

Abstract OBJECTIVE: To collect cases attended in oncology centers in Mexico and to report successful treatments, with complete responses and complications around gestation. MATERIALS AND METHODS: Retrospective case series study including patients with pregnancy-associated acute promyelocytic leukemia attended in different hospitals in the metropolitan area of Mexico City between 1999 and 2021. RESULTS: Seventeen patients with pregnancy-associated acute promyelocytic leukemia were identified, with a median age of 23 years (14-40 years); 7 corresponded to mothers younger than 20 years. In relation to their social environment, 9 had low schooling, 12 were homebased and 13 had a partner at the time of conception. Finally, 11 were originally from an urban area. Patients seen between 1999-2010 were treated with interferon plus cytarabine (7 of 17) or by transfusion support and steroid (2 of 17), in 8 of the 17 cases treatment was initiated with tretinoin in combination with chemotherapy (daunorubicin) as induction therapy. CONCLUSIONS: Treatment of pregnant patients and patients with acute promyelocytic leukemia represents a challenge due to thrombotic and hemorrhagic risk. Although the addition of tretinoin has modified the prognosis of patients with this leukemia, its indication in pregnant women remains controversial, especially because of the risk of teratogenicity.

Age negatively impacts reproduction in high-ranking male rhesus macaques on Cayo Santiago, Puerto Rico.

Based on sexual selection theory, the reproductive potential of male primates is expected to be limited by access to fertile females. Alpha males, the highest ranking males in a social group, are predicted to have better access to mates and produce more offspring until they are no longer dominant, which usually corresponds with age. Little is known about male reproductive senescence independent of rank changes in nonhuman primates. Here, we examine variation in the reproductive success of high-ranking male rhesus macaques on Cayo Santiago. We recorded behavioral data for 21 adult males across 9 social groups during the 2013 mating season. Additionally, we used paternity data from the long-term database to determine the number of offspring each subject sired over his lifetime and during the study period. Older high-ranking males in stable groups had fewer offspring than younger high-ranking males in stable groups in 2013. The low reproductive output for the older males was not a result of lower mating effort, and reproductive output in 2013 was not predicted by total prior reproductive success. Our results provide novel evidence of post-copulatory reproductive senescence in high-ranking male nonhuman primates.

Effect of Season on 25-OH Vitamin D in Serum of Rhesus Monkeys Housed in Puerto Rico.

OBJECTIVE: Vitamin D blood levels have been shown to be partially dependent upon season in temperate climates, however, this same evaluation has not yet been reported in fully tropical climates. Herein, we assessed the vitamin D levels in the blood of Rhesus monkeys housed at the Puerto Rico Caribbean Primate Research Center collected in the island's "summer"(May-October) and "winter" (November-April) months. MATERIALS AND METHODS: In 2006 through 2014, repeated measurements of blood samples were collected from 5 Rhesus monkeys (IACUC-approved) during "summer" and "winter" months to assess 25-OH vitamin D, determined via HPLC. UV-B and UV-A (KJ/m2/day) were measured using a ground based radiometer for these time periods. A paired t-test and a multilevel mixed- effect model approach was performed for data analysis. RESULTS: The difference of the mean serum values of 25-OH vitamin D between seasons showed lower levels during "winter" than "summer" months. About 23% of the variance in levels can be attributed to difference between the monkeys. The means of UV-B and UV-A, as a proxy for sunlight intensity, were greater (over the entire study interval) during the "summer" as opposed to "winter" months (p < 0.001). CONCLUSION: Vitamin D levels were substantially higher in the "summer" rather than the "winter" months. This observation implies that even in fully tropical regions, such as Puerto Rico, time of year can have an influence on vitamin D status. While comparable studies have not been undertaken in humans, it would not be unreasonable to suggest that similar results would be obtained should such a study be done.

Odontogenic abscesses in rhesus macaques (Macaca mulatta) of Cayo Santiago.

OBJECTIVES: Odontogenic abscesses are one of the most common dental diseases causing maxillofacial skeletal lesions. They affect the individual's ability to maintain the dental structures necessary to obtain adequate nutrition for survival and reproduction. In this study, the prevalence and pattern of odontogenic abscesses in relation to age, sex, matriline, and living periods were investigated in adult rhesus macaque skeletons of the free-ranging colony on Cayo Santiago, Puerto Rico. MATERIALS AND METHODS: The skulls used for this study were from the skeletons of 752 adult rhesus macaques, aged 8-31 years, and born between 1951 and 2000. They came from 66 matrilines ranging from 1 to 88 individuals. Fistulae or skeletal lesions caused by odontogenic abscesses drainage, carious lesions, tooth fractures, tooth loss, and alveolar resorption were evaluated visually. RESULTS: Seventy-two specimens (9.57%) had odontogenic abscesses of varying severity. Males had a significantly higher prevalence than females. The prevalence of odontogenic abscesses in several matrilines was significantly higher than in the population as a whole. Animals born between 1950 and 1965 tended to have a higher prevalence of odontogenic abscesses than those born in later periods. DISCUSSION: These results suggest that oral pathologies, such as dental and periodontal abscesses in rhesus macaques are fairly common, which may indicate familial effects interwoven with ecological and social factors. The closeness of the rhesus and human genomes allows insights to understand of the epidemiology of these diseases in the human population. Further assessment of the role played by environmental and familial factors on rhesus oral health and disease are warranted.

Effect of Housing Type on 25 OH Vitamin D in Serum of Rhesus Monkeys.

OBJECTIVE: Vitamin D status is primarily dependent upon sun exposure and dietary sources, however genetic, cultural, and environmental factors can have a modulating role in the measured amount. One under-reported factor is the effect of regular living quarters on the degree of sun exposure. Herein, we assess vitamin D status in the blood of Rhesus monkeys (Macaca mulatta) housed in high amounts of sunlight (corn-cribs), medium sunlight (corrals with shaded areas), and minimal sunlight (quarantine cages). METHODS: Fifty-five male Rhesus monkeys, aged 1 to 31 years were housed in varying amounts of sun exposure at the Caribbean Primate Research Center. Serum was collected and analyzed for 25 OH Vitamin D which is the preferred metabolite for determination of Vitamin D using High Performance Liquid Chromatography (HPLC). RESULTS: 25 OH Vitamin D levels in blood were significantly greater in corn-cribhoused monkeys than in corral or quarantine-housed animals (p > 0.01 and p > 0.001 respectively). Significant differences of serum levels were not found when ages of animals housed in the same environment were compared. CONCLUSION: Monkeys housed in a tropical environment with the greatest amount of exposure to sunlight maintain the highest serum levels of 25 OH vitamin D independent of age. These findings emphasize the importance of documenting the environment in which subjects typically spend their time when Vitamin D results are interpreted.

Population Genetic Structure of the Cayo Santiago Colony of Rhesus Macaques (Macaca mulatta).

The rhesus macaque population at Cayo Santiago increases annually and is in urgent need of control. In-depth assessments of the colony's population genetic and pedigree structures provide a starting point for improving the colony's long-term management program. We evaluated the degree of genetic variation and coefficients of inbreeding and kinship of the Cayo Santiago colony by using pedigree and short tandem repeat (STR) data from 4738 rhesus macaques, which represent 7 extant social groups and a group of migrant males. Information on each animal's parentage, sex, birth date, and date of death or removal from the island were used to generate estimates of mean kinship, kinship value, gene value, genome uniqueness (GU), founder equivalents (fe), and founder genome equivalents (fg). Pedigree and STR analyses revealed that the social groups have not differentiated genetically from each other due to male-mediated gene flow (that is, FST estimates were in the negative range) and exhibit sufficient genetic variation, with mean estimates of allele numbers and observed and expected heterozygosity of 6.57, 0.72, and 0.70, respectively. Estimates of GU, fe, and fg show that a high effective number of founders has affected the colony's current genetic structure in a positive manner. As demographic changes occur, genetic and pedigree matrices need to be monitored consistently to ensure the health and wellbeing of the Cayo Santiago colony.

Familial periodontal disease in the Cayo Santiago rhesus macaques.

Substantial ongoing research continues to explore the contribution of genetics and environment to the onset, extent and severity of periodontal disease(s). Existing evidence supports that periodontal disease appears to have an increased prevalence in family units with a member having aggressive periodontitis. We have been using the nonhuman primate as a model of periodontal disease for over 25 years with these species demonstrating naturally occurring periodontal disease that increases with age. This report details our findings from evaluation of periodontal disease in skulls from 97 animals (5-31 years of age) derived from the skeletons of the rhesus monkeys (Macaca mulatta) on Cayo Santiago. Periodontal disease was evaluated by determining the distance from the base of the alveolar bone defect to the cemento-enamel junction on 1st/2nd premolars and 1st/2nd molars from all four quadrants. The results demonstrated an increasing extent and severity of periodontitis with aging across the population of animals beyond only compensatory eruption. Importantly, irrespective of age, extensive heterogeneity in disease expression was observed among the animals. Linking these variations to multi-generational matriarchal family units supported familial susceptibility of periodontitis. As the current generations of animals that are descendants from these matrilines are alive, studies can be conducted to explore an array of underlying factors that could account for susceptibility or resistance to periodontal disease.

Managing the Cayo Santiago rhesus macaque population: The role of density.

Cayo Santiago is the oldest continuously operating free-ranging rhesus monkey colony in the world. Population control of this colony has historically been carried out by periodic live capture and removal of animals. However, the effect of such a strategy on the size, growth rate, age structure, and sex ratio of the population has not been analyzed. This study reviews past removal data and uses a population projection model to simulate the effects of different removal schemes based on Cayo Santiago demographic data from 2000-2012. The model incorporates negative density-dependence in female fertility, as well as male and female survival rates, to determine the population-level effects of selective removal by age and sex. Modeling revealed that removal of sexually immature individuals has negligible effects on the population dynamics explaining why with an initial population of 1309 in 2000 and annual removals of immature monkeys a mean annual population growth rate of 12% and a final population size of ∼1,435 individuals by 2012 (∼0.009 animal/m(2) ) was observed. With no removals, the population is expected to exhibit dampened oscillations until reaching equilibrium at ∼1,690 individuals (∼0.0111 animal/m(2) ) in 2,100. In contrast, removal of adult females (≥4 yrs) would significantly reduce the population size, but would also promote an increase in population growth rate due to density feedback. A maximum annual production of 275 births is expected when 550 adult females are present in the population. Sensitivity analyses showed that removing females, in contrast to controlling their fertility through invasive treatments would contribute the most to changes in population growth rate. Given the density compensation on fertility, stabilizing the population would require removing ∼80% of the current population of adult females. This study highlights the importance of addressing the population-level density effects, as well as sensitivity analyses, to optimize management strategies.

Translational spatial task and its relationship to HIV-associated neurocognitive disorders and apolipoprotein E in HIV-seropositive women.

HIV-associated neurocognitive disorders (HAND) continue to be a neurological complication of HIV infection in the era of combined antiretroviral therapy. Hippocampal neurodegeneration and dysfunction occurs as a result of HIV infection, but few studies to date have assesses spatial learning and memory function in patients with HAND. We used the Memory Island (MI) test to study the effects of HIV infection, apolipoprotein E (ApoE) allele status, and cerebral spinal fluid (CSF) ApoE protein levels on spatial learning and memory in our cohort of Hispanic women. The MI test is a virtual reality-based computer program that tests spatial learning and memory and was designed to resemble the Morris Water Maze test of hippocampal function widely used in rodent studies. In the current study, HIV-seropositive women (n = 20) and controls (n = 16) were evaluated with neuropsychological (NP) tests, the MI test, ApoE, and CSF ApoE assays. On the MI, the HIV-seropositive group showed significant reduced learning and delayed memory performance compared with HIV-seronegative controls. When stratified by cognitive performance on NP tests, the HIV-seropositive, cognitively impaired group performed worse than HIV-seronegative controls in ability to learn and in the delayed memory trial. Interestingly, differences were observed in the results obtained by the NP tests and the MI test for ε4 carriers and noncarriers: NP tests showed effects of the ε4 allele in HIV-seronegative women but not HIV-seropositive ones, whereas the converse was true for the MI test. Our findings suggest that the MI test is sensitive in detecting spatial deficits in HIV-seropositive women and that these deficits may arise relatively early in the course of HAND.

Associations of cigarette smoking with viral immune and cognitive function in human immunodeficiency virus-seropositive women.

Cigarette smoking alters the immune system and may improve cognitive deficits in neuropsychiatric disorders. Smoking prevalence is high in human immunodeficiency virus (HIV)-infected patients; however, its effect on HIV-associated cognitive impairment remains unknown in the era of antiretroviral treatment. The authors examined associations of smoking with viral immune profile and cognitive function in a cohort of HIV-seropositive women. This observational cross-sectional study included 56 women (36 HIV-seropositive and 20 HIV-seronegative) surveyed with a tobacco questionnaire: the Fagerström Test for Nicotine Dependency. Viral immune status was obtained 6 to 12 months before questioned. Neurocognitive testing (NP) assessed verbal memory, frontal/executive function, psychomotor speed, and motor speed. A reference group of HIV-seronegative women was used to calculate standardized z-scores. Cognitive impairment was classified using a modified American Academy of Neurology criteria, adding an asymptomatic group based on NP tests. Statistics included parametric and nonparametric tests. HIV-seropositive women were more likely to report a history of smoking (P = 0.028). Among them, current smoking correlated with higher plasma viral load (P = 0.048), and history of smoking correlated with lower CD4 cell count (P = 0.027). The authors observed no associations between cognitive impairment and either current or past history of smoking and no differences in neurocognitive domain scores between HIV-seropositive and -seronegative women or between those with and without a history of smoking. However, restricting analysis to HIV-seropositives showed a significant better performance on the frontal/executive domain in those with history of smoking. In summary, history of smoking correlated with better frontal/executive cognitive domain performance in HIV-seropositive women and with worse viral immune profile.

Prevalence of human immunodeficiency virus-associated cognitive impairment in a group of Hispanic women at risk for neurological impairment.

Human immunodeficiency virus (HIV)-associated cognitive impairment, a significant cause of morbidity, affects up to 30% of HIV-infected people. Its prevalence doubled as patients began to live longer after the introduction of highly active retroviral therapy. Women are now one of the fastest growing groups with acquired immunodeficiency syndrome (AIDS) in the United States and Puerto Rico, but relatively little is known about the prevalence and characteristics of cognitive dysfunction in HIV-infected women. In this study the authors investigated its prevalence in a group of HIV-1-seropositive Hispanic women in Puerto Rico. Forty-nine women with a nadir CD4 cell count of < or = 500 cells/mm3 were enrolled. Cognitive impairment was defined according to the American Academy of Neurology criteria for HIV dementia as modified to identify an "asymptomatic cognitively impaired" group. Observed prevalence was compared with prevalence in other populations in United States, Europe, and Australia. Differences in clinical markers and neuropsychological test performance among the cohort stratified by cognitive impairment were tested. Cognitive impairment was observed in 77.6% (38/49) of cases; asymptomatic cognitive impairment in 32.7% (16/49); minor cognitive motor disorders in 16.3% (8/49); and HIV-associated dementia (HAD) in 28.6% (14/49). Cognitive impairment did not correlate with age, CD4 cell count, viral load, or treatment modality. The cross-sectional prevalence of HIV-associated cognitive impairment was 77.6% (28.6% for HAD). These findings should enhance awareness of the prevalence of HIV-associated cognitive impairment, both clinically apparent and "asymptomatic," in Hispanic women and lead to improvements in areas such as education and compliance and to reevaluation of treatment interventions.

Herpes B-virus seroreactivity in a colony of Macaca mulatta: data from the Sabana Seca Field Station, a new specific pathogen-free program.

The demand for B-virus-free animals for biomedical research is increasing, while at the same time the availability of such animals is decreasing. The establishment of Specific Pathogen-Free (SPF) breeding macaque colonies is a priority of the National Institutes of Health. Nevertheless, it is well known that seroreactivity to B-virus can be difficult to interpret, particularly as it can vary over time in a single animal. The aim of the present study was to implement a reliable algorithm to examine B-virus reactivity among the rhesus monkey population of the Caribbean Primate Research Center. The sensitivity and specificity of our assay were determined using reports from two different laboratories as references. Whereas 95.4% of animals showed consistent serological status and 4.6% of animals recruited to this SPF program showed serovariability to B-virus over the initial 2 years of examination. Implications for all SPF programs are discussed in this article.

El enclaustramiento cromósomico, la frecuencia de mitosis y su relación con la proporción Carnoy/KCL / The enclosed chromosome, the frecuency of mitoses and their relationship with the Carnoy/KCL ratio

Se investigó el efecto de diferentes proporciones de Carnoy/KCI sobre la frecuencia de mitosis enclaustradas por los residuos de citoplasma y la relación de éstas con el número total de mitosis. Se demostró que la disminución de la proporción (de 1 a 0.5, 0.4 y 0.3) se asoció con una disminución de la frecuencia de mitosis enclaustradas y un aumento en el número total de mitosis. El resultado de esta divergencia, que denominamos Mitosis Efectiva (ME), con la proporción de 1 fue de 0.32 + - 0.24 por ciento (X + - DE) y con proporciones menores de 1 fue de 3.44 + - 2.25 por ciento (p<0.01). Este aumento se observó exclusivamente cuando el KCI se agregó a 37§C; la Microdosis (MD) de Carnoy 1 22§C se añadió al inicio de la incubación con KCI a 37§C y se incluyó un periodo de reposo de 10 minutos a 22§C entre las dos primeras fijaciones con Carnoy a 22§C. Se suprimió el beneficio de la disminución de la proporción sobre el enclaustramiento y la frecuencia de mitosis, cuando se omitió la MD o el reposo, la MD se agregó al final de la incubación con KCI o a 4§C y el KCI o el Carnoy se añadieron a 22§C o 4§C respectivamente.