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As the SARS-CoV-2 virus spread throughout the world, millions of positive cases of COVID-19 were registered and, even though there are millions of people already vaccinated against SARS-CoV-2, a large part of the global population remains vulnerable to contracting the virus. Massive nasopharyngeal sample collection in Puerto Rico at the beginning of the pandemic was limited by the scarcity of trained personnel and testing sites. To increase SARS-CoV-2 molecular testing availability, we evaluated the diagnostic accuracy of self-collected nasal, saliva, and urine samples using the TaqPath reverse transcription polymerase chain reaction (RT-PCR) COVID-19 kit to detect SARS-CoV-2. We also created a colorimetric loop-mediated isothermal amplification (LAMP) laboratory developed test (LDT) to detect SARS-CoV-2, as another strategy to increase the availability of molecular testing in community-based laboratories. Automated RNA extraction was performed in the KingFisher Flex instrument, followed by PCR quantification of SARS-CoV-2 on the 7500 Fast Dx RT-PCR using the TaqPath RT-PCR COVID-19 molecular test. Data was interpreted by the COVID-19 Interpretive Software from Applied Biosystems and statistically analyzed with Cohen's kappa coefficient (k). Cohen's kappa coefficient (k) for paired nasal and saliva samples showed moderate agreement (0.52). Saliva samples exhibited a higher viral load. We also observed 90% concordance between LifeGene-Biomarks' SARS-CoV-2 Rapid Colorimetric LAMP LDT and the TaqPath RT-PCR COVID-19 test. Our results suggest that self-collected saliva is superior to nasal and urine samples for COVID-19 testing. The results also suggest that the colorimetric LAMP LDT is a rapid alternative to RT-PCR tests for the detection of SARS-CoV-2. This test can be easily implemented in clinics, hospitals, the workplace, and at home; optimizing the surveillance and collection process, which helps mitigate global public health and socioeconomic upheaval caused by airborne pandemics.
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COVID-19 , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , SARS-CoV-2 , Saliva , Manejo de Espécimes , Humanos , Saliva/virologia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , COVID-19/diagnóstico , COVID-19/virologia , COVID-19/urina , Técnicas de Amplificação de Ácido Nucleico/métodos , Manejo de Espécimes/métodos , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , RNA Viral/análise , RNA Viral/urina , RNA Viral/genética , RNA Viral/isolamento & purificação , Teste de Ácido Nucleico para COVID-19/métodos , Sensibilidade e Especificidade , Porto Rico/epidemiologia , Teste para COVID-19/métodosRESUMO
Differentially methylated regions (DMRs) can be used as head and neck squamous cell carcinoma (HNSCC) diagnostic, prognostic and therapeutic targets in precision medicine workflows. DNA from 21 HNSCC and 10 healthy oral tissue samples was hybridized to a genome-wide tiling array to identify DMRs in a discovery cohort. Downstream analyses identified differences in promoter DNA methylation patterns in oral, laryngeal and oropharyngeal anatomical regions associated with tumor differentiation, nodal involvement and survival. Genome-wide DMR analysis showed 2,565 DMRs common to the three subsites. A total of 738 DMRs were unique to laryngeal cancer (n=7), 889 DMRs were unique to oral cavity cancer (n=10) and 363 DMRs were unique to pharyngeal cancer (n=6). Based on the genome-wide analysis and a Gene Ontology analysis, 10 candidate genes were selected to test for prognostic value and association with clinicopathological features. TIMP3 was associated with tumor differentiation in oral cavity cancer (P=0.039), DAPK1 was associated with nodal involvement in pharyngeal cancer (P=0.017) and PAX1 was associated with tumor differentiation in laryngeal cancer (P=0.040). A total of five candidate genes were selected, DAPK1, CDH1, PAX1, CALCA and TIMP3, for a prevalence study in a larger validation cohort: Oral cavity cancer samples (n=42), pharyngeal cancer tissues (n=25) and laryngeal cancer samples (n=52). PAX1 hypermethylation differed across HNSCC anatomic subsites (P=0.029), and was predominantly detected in laryngeal cancer. Kaplan-Meier survival analysis (P=0.043) and Cox regression analysis of overall survival (P=0.001) showed that DAPK1 methylation is associated with better prognosis in HNSCC. The findings of the present study showed that the HNSCC subsites oral cavity, pharynx and larynx display substantial differences in aberrant DNA methylation patterns, which may serve as prognostic biomarkers and therapeutic targets.
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INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic revealed a worldwide lack of effective molecular surveillance networks at local, state, and national levels, which are essential to identify, monitor, and limit viral community spread. SARS-CoV-2 variants of concern (VOCs) such as Alpha and Omicron, which show increased transmissibility and immune evasion, rapidly became dominant VOCs worldwide. Our objective was to develop an evidenced-based genomic surveillance algorithm, combining reverse transcription polymerase chain reaction (RT-PCR) and sequencing technologies to quickly identify highly contagious VOCs, before cases accumulate exponentially. METHODS: Deidentified data were obtained from 508,969 patients tested for coronavirus disease 2019 (COVID-19) with the TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) in four CLIA-certified clinical laboratories in Puerto Rico (n = 86,639) and in three CLIA-certified clinical laboratories in the United States (n = 422,330). RESULTS: TaqPath data revealed a frequency of S Gene Target Failure (SGTF) > 47% for the last week of March 2021 in both, Puerto Rico and US laboratories. The monthly frequency of SGTF in Puerto Rico steadily increased exponentially from 4% in November 2020 to 47% in March 2021. The weekly SGTF rate in US samples was high (>8%) from late December to early January and then also increased exponentially through April (48%). The exponential increase in SGFT prevalence in Puerto Rico was concurrent with a sharp increase in VOCs among all SARS-CoV-2 sequences from Puerto Rico uploaded to Global Influenza Surveillance and Response System (GISAID) (n = 461). Alpha variant frequency increased from <1% in the last week of January 2021 to 51.5% of viral sequences from Puerto Rico collected in the last week of March 2021. CONCLUSIONS: According to the proposed evidence-based algorithm, approximately 50% of all SGTF patients should be managed with VOCs self-quarantine and contact tracing protocols, while WGS confirms their lineage in genomic surveillance laboratories. Our results suggest this workflow is useful for tracking VOCs with SGTF.
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COVID-19 , SARS-CoV-2 , Sequência de Bases , COVID-19/diagnóstico , COVID-19/epidemiologia , Humanos , Medicina de Precisão , SARS-CoV-2/genética , Estados Unidos/epidemiologiaRESUMO
We previously reported a multigene family of monodomain Kunitz proteins from Echinococcus granulosus (EgKU-1-EgKU-8), and provided evidence that some EgKUs are secreted by larval worms to the host interface. In addition, functional studies and homology modeling suggested that, similar to monodomain Kunitz families present in animal venoms, the E. granulosus family could include peptidase inhibitors as well as channel blockers. Using enzyme kinetics and whole-cell patch-clamp, we now demonstrate that the EgKUs are indeed functionally diverse. In fact, most of them behaved as high affinity inhibitors of either chymotrypsin (EgKU-2-EgKU-3) or trypsin (EgKU-5-EgKU-8). In contrast, the close paralogs EgKU-1 and EgKU-4 blocked voltage-dependent potassium channels (Kv); and also pH-dependent sodium channels (ASICs), while showing null (EgKU-1) or marginal (EgKU-4) peptidase inhibitory activity. We also confirmed the presence of EgKUs in secretions from other parasite stages, notably from adult worms and metacestodes. Interestingly, data from genome projects reveal that at least eight additional monodomain Kunitz proteins are encoded in the genome; that particular EgKUs are up-regulated in various stages; and that analogous Kunitz families exist in other medically important cestodes, but not in trematodes. Members of this expanded family of secreted cestode proteins thus have the potential to block, through high affinity interactions, the function of host counterparts (either peptidases or cation channels) and contribute to the establishment and persistence of infection. From a more general perspective, our results confirm that multigene families of Kunitz inhibitors from parasite secretions and animal venoms display a similar functional diversity and thus, that host-parasite co-evolution may also drive the emergence of a new function associated with the Kunitz scaffold.
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Equinococose/metabolismo , Equinococose/parasitologia , Proteínas de Helminto/metabolismo , Interações Hospedeiro-Parasita/fisiologia , Inibidores de Serina Proteinase/fisiologia , Animais , Echinococcus granulosus , Gânglios Espinais/efeitos dos fármacos , Modelos Moleculares , Técnicas de Patch-Clamp , Filogenia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/efeitos dos fármacos , Ratos , Ratos Wistar , Inibidores de Serina Proteinase/farmacologia , Canais de Sódio Disparados por Voltagem/efeitos dos fármacosRESUMO
BACKGROUND: HPV-16 modifies the overall survival (OS) of patients with oropharyngeal cancer (OPSCC). HPV-16 has been established as risk factor for OPSCC, but HPV-16 infection may also reside in the larynx and oral cavity. We evaluated HPV-16 status on OS of Head and Neck Squamous Cell Carcinoma (HNSCC) patients. METHODS: HPV-16 infection was confirmed by amplification of E6 and E7 viral oncogenes through PCR assay and E6 IHC in 185 HNSCC samples. Associations between HPV-16 status and clinicopathological parameters were performed using Fisher's exact test and x(2). Survival analysis was completed using Kaplan-Meier estimator and multivariate Cox regression analysis. RESULTS: OS of HPV-16 positive patients was longer compared to HPV-16 negative patients (P = 0.002). HPV-16 positive tumors of the larynx (LSCC) and pharynx (PSCC) showed improved OS compared to HPV-16 negative tumors. Also, HPV-16 positive patients exposed to radiotherapy presented a better survival. CONCLUSIONS: HPV-16 status has a positive prognostic value in HNSCC. Addition of HPV-16 status to the TNM staging can provide better assessment in prognosis and guide treatment for HNSCC patients.
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Se describe la dermatitis herpetiforme como una dermatosis ampollar de evolución crónica que puede aparecer en cualquier edad. Se presenta con una frecuencia de 10 a 39 por cada 100.000 personas, siendo menos frecuente su aparición en niños. La dermatitis herpetiforme se caracteriza por una erupción papulovesicular acompañada de prurito intenso. Se presenta el caso de un paciente masculino de 2 años de edad con un brote de lesiones vesicoampollares de aspecto herpetiforme, de un mes de evolución. Se indica dapsona a una dosis de 2 mg/kg/día, obteniéndose una excelente respuesta al tratamiento. El interés científico del caso radica en la edad del paciente, por su escasa incidencia en edades infantiles, en el diagnóstico clínico realizado y en la respuesta inmediata al tratamiento impuesto.
We describe the herpes-kind dermatitis like a chronic blistery dermatosis that can appear at any age. Its frequency ranges from 10 to 39 per 100 000 persons, being less frequent in children. The herpes-kind dermatitis is characterized by a bullous blistery rash accompanied by an intense pruritus. We present the case of a male patient aged 2 years with an outbreak of herpes-kind vesical blistery lesions, and evolution of a month. We indicated a treatment of 2mg/kg a day dapsone, obtaining an excellent answer to the treatment. The scientific importance of the case is in the patient´s age, because of the disease´s scarce incidence in infantile ages, in the clinical diagnosis and the fast answer to the indicated treatment.
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Introducción: la cirrosis hepática se caracteriza por una fase asintomática o compensada, seguida de una rápida progresión por el desarrollo de complicaciones o descompensada, lo que determina diferentes estadios evolutivos. Objetivo: caracterizar los pacientes cirróticos atendidos en el Servicio de Gastroenterología del Hospital Militar Docente Dr. Mario Muñoz Monroy, en el período comprendido entre enero de 2009 a diciembre de 2010. Métodos: se realizó un estudio descriptivo transversal. Se tuvieron en cuenta variables clínicas necesarias para clasificar los pacientes según las etapas contempladas en el consenso de Baveno IV. Se aplicaron procedimientos de la estadística descriptiva. Resultados: se estudiaron 41 pacientes, con predominio de masculinos (82,9 %), con edad promedio de 51,9 ± 9,2 años. La astenia fue el principal motivo de consulta en la fase compensada; los pacientes presentaron una enfermedad compensada en su gran mayoría, de acuerdo al estadio clínico de la enfermedad según criterios de Baveno IV Consenso Metodológico sobre Diagnóstico y Tratamiento de la Hipertensión Portal (56,1 %). Conclusiones: con la aplicación de los criterios del consenso de Baveno IV se logra la adecuada clasificación clínica del paciente cirrótico que permite una terapéutica oportuna en beneficio de estos.
Introduction: liver cirrhosis is characterized by an asymptomatic or compensated stage, followed by a fast progression for the development of complications or decompensated stage, determining different evolutionary stages. Objective: characterizing cirrhotic patients attended at the Gastroenterology Service of the Teaching Military Hospital Dr. Mario Muñoz Monroy, in the period from January 2009 to December 2010. Methods: We carried out a crossed descriptive study, taking into account clinical variables necessary to classify the patients according to the stages contemplated at Baveno IV Consensus. The procedures of the descriptive statistics were applied. Results: 41 patients were studied, with a predomination of the male ones (82,9 %), average age 51,9 ± 9,2 years. Asthenia was the main reason of the consultation in the compensated stage. Most of the patients presented the compensated disease taking into account the clinical stage of the disease according to Baveno VI Methodological Consensus on Diagnostic and Treatment of the Portal Hypertension (56,1 %). Conclusions: with the application of the Baveno IV consensus criteria we arrived to the adequate clinical classification of the cirrhotic patients allowing an opportune therapeutic on behalf of them.
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In 2011, research educators face significant challenges. Training programs in Clinical and Translational Research need to develop or enhance their curriculum to comply with new scientific trends and government policies. Curricula must impart the skills and competencies needed to help facilitate the dissemination and transfer of scientific advances at a faster pace than current health policy and practice. Clinical and translational researchers are facing also the need of new paradigms for effective collaboration, and resource sharing while using the best educational models. Both government and public policy makers emphasize addressing the goals of improving health quality and elimination of health disparities. To help achieve this goal, our academic institution is taking an active role and striving to develop an environment that fosters the career development of clinical and translational researchers. Consonant with this vision, in 2002 the University of Puerto Rico, Medical Sciences Campus School of Health Professions and School of Medicine initiated a multidisciplinary post-doctoral Master of Science in Clinical Research focused in training Hispanics who will address minority health and health disparities research. Recently, we proposed a curriculum revision to enhance this commitment in promoting competency-based curricula for clinician-scientists in clinical and translational sciences. The revised program will be a post-doctoral Master of Science in Clinical and Translational Research (MCTR), expanding its outreach by actively engaging in establishing new collaborations and partnerships that will increase our capability to diversify our educational efforts and make significant contributions to help reduce and eliminate the gap in health disparities.
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Disparidades em Assistência à Saúde , Hispânico ou Latino , Saúde das Minorias , Pesquisa Translacional Biomédica , HumanosRESUMO
The encapsulation of insulin into different kinds of materials for noninvasive delivery is an important field of study because of the many drawbacks of painful needle and syringe delivery such as physiological stress, infection, and local hypertrophy, among others (Khafagy, E.-S.; et al. Adv. Drug Delivery Rev. 2007, 59 (15), 1521-1546). A stable, robust, nontoxic, and viable noninvasive carrier for insulin delivery is needed. We present a new approach for protein nanoencapsulation using layered zirconium phosphate (ZrP) nanoparticles produced without any preintercalator present. The use of ZrP without preintercalators produces a highly pure material, without any kinds of contaminants, such as the preintercalator, which can be noxious. Cytotoxicity cell viability in vitro experiments for the ZrP nanoparticles show that ZrP is not toxic, or harmful, in a biological environment, as previously reported for rats (Zhu, Z. Y.; et al. Mater. Sci. Forum 2009, 620-622, 307-310). Contrary to previous preintercalator-based methods, we show that insulin can be nanoencapsulated in ZrP if a highly hydrate phase of ZrP with an interlayer distance of 10.3 Å (10.3 Å-ZrP or θ-ZrP) is used as a precursor. The intercalation of insulin into ZrP produced a new insulin-intercalated ZrP phase with about a 27 A interlayer distance, as determined by X-ray powder diffraction, demonstrating a successful nanoencapsulation of the hormone. The in vitro release profile of the hormone after the intercalation was determined and circular dichroism was used to study the hormone stability upon intercalation and release. The insulin remains stable in the layered material, at room temperature, for a considerable amount of time, improving the shell life of the peptidic hormone. This type of material represents a strong candidate to developing a noninvasive insulin carrier for the treatment of diabetes mellitus.
Assuntos
Hipoglicemiantes/química , Insulina/química , Substâncias Intercalantes/química , Nanocápsulas/química , Nanotecnologia/métodos , Zircônio/química , Animais , Neoplasias da Mama/tratamento farmacológico , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Feminino , Humanos , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Microscopia Eletrônica de Varredura , Pâncreas/metabolismo , Ratos , Espectroscopia de Infravermelho com Transformada de Fourier , Células Tumorais CultivadasRESUMO
La rosácea es una enfermedad inflamatoria crónica, que afecta fundamentalmente zonas centrales de la cara. Es más frecuente en el sexo femenino entre la 3ra y 5ta década de vida. Se presenta un caso que padece de rosácea grado III desde hace 10 años. Esta paciente llevó durante largo tiempo múltiples tratamientos sin resolver, ni mejorar el cuadro clínico. Se le pone tratamiento oral y tópico con retinoides, observándose mejoría evidente a los 6 meses y escasas reacciones adversas.
Rosacea is a chronic inflammatory disease, affecting mainly the central areas of the face. It is more frequently in the female genre between the 3 rd and the 5 th decade of life. We present a case of a patient suffering III grade rosacea for 10 years. This patient received several treatments for a long time without solving, or improving her clinical features. She was treated orally and topically with retinoids, and her condition evidently improved in six months, with scarcely adverse reactions.
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The SMADs are a group of interrelated proteins that mediate transforming growth factor beta (TGF-beta) signaling. Upon TGF-beta binding the TGF-beta type I receptor phosphorylates Smad2 and Smad3, which then complex with Smad4 and translocate to the nucleus, with subsequent activation of target genes. Disruption of TGF-beta signaling is thought to contribute to the development of head and neck squamous cell carcinomas (HNSCC). Alterations in the function of the DPC4/Smad4 tumor suppressor gene have been found to inactivate TGF-beta signaling in several tumor types. For example, DPC4/Smad4 is lost or mutated in colorectal, pancreatic, and esophageal cancers. In addition, DPC4/Smad4 transcriptional activity and TGF-beta ability to inhibit DNA synthesis is blocked by the E7 protein of the human papillomavirus type 16 (HPV16) in cervical carcinoma cell lines. HPV16 infection is a risk factor for the development of a subset of HNSCC. This study was undertaken to investigate a potential correlation between expression of components of the TGF-beta signaling pathway and HPV16 status in HNSCC tumors. We examined the expression of TGF-beta signaling proteins Smad2, Smad2-P, and Smad4 by immunohistochemistry in 27 HPV16-negative and 16 HPV16-positive HNSCCs. We compared the expression patterns and assessed their relationship to HPV16 status. No significant differences were detected between HPV16-positive and HPV16-negative tumors in the expression of Smad2 and Smad2-P. Smad4 expression, however, was decreased in 56% of the HPV16-positive tumors and in 39% of HPV16-negative tumors. This difference was statistically significant (P = 0.01) suggesting that loss of Smad4 expression may be involved in HPV16-induced carcinogenesis of HNSCC.
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Carcinoma de Células Escamosas/patologia , Proteínas de Ligação a DNA/biossíntese , Neoplasias de Cabeça e Pescoço/patologia , Infecções por Papillomavirus/patologia , Transativadores/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virologia , DNA Viral/genética , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Oncogênicas Virais/genética , Papillomaviridae/genética , Papillomaviridae/crescimento & desenvolvimento , Proteínas E7 de Papillomavirus , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Proteínas Repressoras/genética , Transdução de Sinais , Proteína Smad4 , Fator de Crescimento Transformador beta/metabolismoRESUMO
OBJECTIVE: The purpose of this study is to characterize head and neck squamous cell carcinoma (HNSCC) in the Puerto Rican population. This is a follow-up to our initial published report on the first 134 patients. Specifically, demographic characteristics, stage at presentation, initial treatment given, and rate of recurrence were studied. METHODS: Relevant data was obtained from 445 histologically confirmed HNSCC cases identified through the University of Puerto Rico School of Medicine Otolaryngology Department Head and Neck Cancer Clinics between August 1993 and January 2003. Data collected after informed consent included demographic factors (sex, age, areas of residence, income); risk factors (occupation, alcohol intake, cigarette usage); and pathological variables (tumor location, histopathology, stage at presentation, current disease status, tumor recurrence). RESULTS: The average age at diagnosis was 64.0 years (range 18-98); 84.5% of the patients were male, 16% were females. The most frequent anatomical sites of the primary tumor were the larynx (36.4%) and the oral cavity (29.9%). The majority of patients (61.1%) presented with advanced stage (III-IV) disease at the time of diagnosis and over half (55.5%) had moderately-differentiated tumors. Most patients had less than 12 years of formal education (81.2%). Prolonged use of tobacco and alcohol identified in 88.1% and 79.8% of patients, respectively. The most frequent therapeutic modality used was radiation therapy followed by the combination of radiation and surgery. Twenty five percent of the cases experienced a recurrence of disease during the follow-up period. CONCLUSIONS: These findings emphasize the need for early detection programs for HNSCC in Puerto Rican patients given the high rate of advanced-stage disease at time of diagnosis. The key role of heavy alcohol intake and tobacco use as risk factors in the development of HNSCC is once again highlighted.
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Carcinoma de Células Escamosas/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Idoso , Alcoolismo/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Demografia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Incidência , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Recidiva Local de Neoplasia , Porto Rico/epidemiologia , Fatores de Risco , Fumar/epidemiologiaRESUMO
This study comprised 134 patients who had developed head and neck squamous carcinoma (HNSCC), and attended the cancer clinics of the Otolaryngology Department at the Isaac González Martínez Oncologic Hospital between August 1993 and November 1995. In-person interviews, and medical record review of the HNSCC patients provided data on demography, family history of cancer, history of a second primary cancer, history of environmental, tobacco and ethanol exposure, and current disease status. The average age at the time of diagnosis was 62.3 (range 18-94), and eighty percent of the subjects were male. Most (59 per cent) of the patients had moderately differentiated tumors and 14 per cent had a recurrence of the carcinoma. The most frequent primary site in males was the laryngeal area, and the oral cavity in females. Exposure to alcohol and smoking were identified as predisposing factors in 95 per cent of the patients.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Fatores Etários , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias Bucais , Neoplasias Laríngeas/epidemiologia , Porto Rico , Fatores de Risco , Segunda Neoplasia Primária/epidemiologia , Fatores Sexuais , Fumar/efeitos adversosRESUMO
La leucemia linfática (CLL) rara vez se transforma a leucemia aguda. Recientemente se ha descrito una transformación prolinfocítica. Se reportan los estudios morfológicos, microscopía electrónica, marcadores de superficie y análysis de DNA de un paciente con esta transformación. El paciente un hombre de 80 años presentó con esplenomegalia, anemia y trombocitopenia. el recuento de células blancas fue 100,00/mm3 con 90% linfocitos pequeños y maduros. La respuesta a clorambucil y prednisona, COP, CHOP fue pobre. Se le practicó una esplenectomía y el bazo tenía linfocitos maduros y prolinfocitos. El curso postoperatorio fue complicado pero recobró y el hemograma mejoró. Tres meses después de cirugía estaba asintomático y tenía 32,900/mm3 células blancas con 82% linfocitos pequeños. En el transcurso de un mes se enfermó con dolores óseos y el contaje subió a 256,000 con 65% de células inmaduras. Citometría de flujo demostró 75% de células positivas para el marcador B1, 77% para B4, 76% para I3 consistente con una proliferación de células B. Calla (CD10) fue 50.3%. Análisis de DNA demostró que 54% de las células estaban en GO + G1, 24% in S y 22% en G2 + M, confirmando una proliferación activa en contraste con CLL. La microscopía electrónica demostró células grandes con muchas mitocondrias, núcleo grande, cromatina dispersa y nucleolo prominente. el paciente se trató con CHOP-Bleomicina y tuvo una buena respuesta con remisión periférica después de cuatro ciclos de tratamiento. Esto sin embargo duró poco y relapsó con contaje de 529,000/mm3. Se le administró terapia con cisplatinum, citarabina, dexametasona y vincristina y fue seguido por leucaferesis. esta transformación debe distinguirse de leucemia aguda y el síndrome de Ritcher's aunque probablemente son evoluciones similares. Este es el primer paciente reportado en Puerto Rico con esta transformación aunque indudablemente ha habido otros