Primer caso reportado en Panamá de: Síndrome de Baraitser Winter

El síndrome cerebro-frontal-facial de Baraitser-Winter (BWCFF) se origina a partir de mutaciones sin sentido, heterocigóticas, en uno de los dos genes ubicuos que codifican la actina citoplásmica, ya sea ACTB o ACTG1. Este síndrome es una combinación de malformaciones faciales y cerebrales. Entre las malformaciones faciales que podemos observar, destacan el coloboma de iris, la ptosis bilateral, el hipertelorismo, el puente nasal ancho y los pliegues epicánticos prominentes. Las malformaciones cerebrales incluyen la paquigiria, la heterotopia de banda subcortical y las anomalías del cuerpo calloso. En este contexto, presentamos el caso de una niña de 11 años que presentaba algunos rasgos faciales distintivos, además de malformaciones cerebrales, baja estatura, discapacidad cognitiva moderada, y retraso del habla y lenguaje. Mediante secuenciación por exoma clínico dirigido, se identificó una variante sin sentido heterocigota de Novo en ACTB: c.617G>A (p. Arg206Gln). (provisto por Infomedic International)

The Baraitser-Winter cerebral-front-facial syndrome (BWCFF) is caused by heterozygous nonsense mutations in one of the two ubiquitous genes encoding cytoplasmic actin, either ACTB or ACTG1. The syndrome combines facial and cerebral malformations. Among the facial malformations that can be observed are iris coloboma, bilateral ptosis, hypertelorism, broad nasal bridge, and prominent epicanthic folds. The cerebral malformations include pachygyria, subcortical band heterotopia, and anomalies of the corpus callosum. We present the case of an 11-year-old girl who had some distinctive facial features, as well as cerebral malformations, short stature, moderate cognitive disability, and speech and language delay. Targeted clinical exome sequencing identified a heterozygous de novo nonsense variant in ACTB: c.617G>A (p. Arg206Gln). (provided by Infomedic International)

El Síndrome De Down al pasar de los años

El síndrome de Down es una condición genética muy conocida, causada por una alteración cromosómica numérica caracterizada por la presencia de un tercer cromosoma 21. Tiene una distribución mundial, en todas las razas y data de hace cientos de años. Bajo el lema "NOS DECIDIMOS", este año se conmemora el Día Mundial del Síndrome de Down, como cada 21 de marzo desde su instauración en el 2011. Este lema se originó en los temas discutidos durante la Convención de las Naciones Unidas sobre los Derechos de las Personas con Discapacidad y fue escogido con el propósito de enfatizar la necesidad de que las personas con este síndrome se involucren en la toma de sus propias decisiones, siendo este un derecho humano básico. El Día Mundial del Síndrome de Down brinda la oportunidad de ampliar panoramas, apoyar la igualdad y la inclusión. (provisto por Infomedic International)

Down syndrome is a well-known genetic condition caused by a numerical chromosomal alteration due to the presence of a third chromosome 21. It has a worldwide distribution, in all races and has been known for hundreds of years. Under the slogan WE DECIDE, this year we commemorate the World Down Syndrome Day, as every 21st of March since it was established in 2011. This motto was originated during the United Nations Convention on the Rights of Persons with Disabilities, and it was selected to emphasize the need for people with this syndrome to be involved in their decision-making process, as it is a basic human right. The World Down Syndrome Day provides an opportunity to broaden panoramas, support equality and inclusion. (provided by Infomedic International)

High-risk human papillomavirus (HPV) DNA sequences in metaplastic breast carcinomas of Mexican women.

BACKGROUND: Metaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas. The present study examined 20 surgical specimens of metaplastic breast carcinomas, for the presence of high-risk Human papillomavirus (HPV), which is suspected to be a potential carcinogenic agent for breast carcinoma. METHODS: Mastectomy specimens from patients harboring metaplastic breast carcinoma, as defined by the World Health Organization (WHO), and who attended the Instituto Nacional de Cancerologia in Mexico City, were retrieved from the files of the Department of Pathology accumulated during a 16-year period (1995-2008). Demographic and clinical information was obtained from patients' medical records. DNA was extracted from formalin-fixed, paraffin-embedded tumors and HPV type-specific amplification was performed by means of Polymerase chain reaction (PCR). Quantitative Real-time (RT) PCR was conducted in HPV positive cases. Statistically, the association of continuous or categorical variables with HPV status was tested by the Student t, the Chi square, or Fisher's exact tests, as appropriate. RESULTS: High-risk HPV DNA was detected in eight (40%) of 20 metaplastic breast carcinomas: seven (87.5%) HPV-16 and one (12.5%) HPV-18. Mean age of patients with HPV-positive cases was 49 years (range 24-72 years), the same as for HPV-negative cases (range, 30-73 years). There were not striking differences between HPV + and HPV- metaplastic carcinomas regarding clinical findings. Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR). CONCLUSIONS: High-risk HPV has been strongly associated with conventional breast carcinomas, although the subtle mechanism of neoplastic transformation is poorly understood. In Mexican patients, the prevalence of HPV infection among metaplastic breast carcinomas is higher than in non-metaplastic ones, as so the HPV viral loads; notwithstanding, HPV viral loads show wide variation and remain even lower than cervical and other non-cervical carcinomas, making it difficult to assume that HPV could play a key role in breast carcinogenesis. Further studies are warranted to elucidate the meaning of the presence of high-risk HPVDNA in breast carcinomas.

Argon plasma coagulation and hyperbaric oxygen therapy in chronic radiation proctopathy, effectiveness and impact on tissue toxicity.

BACKGROUND: chronic radiation proctopathy (CRP) is associated with recurrent rectal bleeding and transfusional requirements. Argon plasma coagulation (APC) and hyperbaric oxygen therapy (HOT) have been shown to be effective in the control of CRP. No prospective comparisons have been reported between these treatments. AIM: the aim was to evaluate the effectiveness, safety and impact on tissue toxicity of APC compared to HOT in patients with CRP. MATERIAL AND METHODS: a prospective study for evaluating treatment response was conducted. Patients with cervical cancer and CRP with rectal bleeding were recruited. They had not received previous treatment. Collected data included: demographics, previous radiation dosage, duration and severity of rectal bleeding. Hemoglobin, transfusional requirements, and tissue toxicity (SOMA LENT questionnaire) at baseline and at 1, 2, and 3 months follow up were recorded. RESULTS: thirty-one patients were included, 14 in the APC group and 17 in the HOT group. No response was noted in 13 and 18% of patients in the APC and HOT group respectively (p = NS). At the 1 and 2 months follow-up, the APC group showed a significantly better response in terms of transfusional requirements (0.6 vs. 3.4 and 0.7 vs. 2.5) and tissue toxicity score (5.3 vs. 8.6 and 3.8 vs. 7.248). After 3 months, both groups showed further improvement in all parameters without significant differences between them. CONCLUSIONS: APC and HOT were effective, safe and decreased the tissue toxicity scores in patients with CRP. However, response rate was higher and faster in the APC group.

Argón plasma y oxígeno hiperbárico para el control de la rectorragia crónica secundaria a la proctopatía por radiación / Argon plasma coagulation and hyperbaric oxygen therapy in chronic radiation proctopathy, effectiveness and impact on tissue toxicity

Introducción: la proctopatía por radiación (PPR) se asocia con rectorragía recurrente y requerimientos de trasfusiones. La coagulación con argón plasma (APC) y la terapia con oxígeno hiperbárico (HOT) han sido efectivas en el control de la PPR. No hay estudios prospectivos comparativos entre ambas técnicas. Objetivo: el objetivo del estudio es evaluar la efectividad, seguridad y el impacto en la toxicidad tisular de la APC comparado con el HOT en los pacientes con PR. Material y métodos: se realizó un estudio prospectivo para evaluar la respuesta al tratamiento. Se incluyeron a pacientes con cáncer cervicouterino y PPR con rectorragia recurrente, sin haber recibido tratamientos previos. Se tomaron datos demográficos, dosis de radiación, duración y severidad de la rectorragia, niveles de hemoglobina, requerimientos de trasfusiones y la toxicidad tisular (Cuestionario de SOMA-LENT) al inicio, y a los 1, 2 y 3 meses del tratamiento. Resultados: se incluyeron a 31 pacientes con PPR, 14 en el grupo de APC y 17 en el grupo de HOT. No hubo respuesta en el 13 y 18% de los pacientes en el grupo de APC y OHT respectivamente (p = NS). Al primer y segundo mes de seguimiento, el grupo APC mostró una mejoría significativa en los parámetros de requerimientos trasfusionales (0,6 vs. 3,4 y 0,7 vs. 2,5) y en la toxicidad tisular (5,3 vs. 8,6 y 3,8 vs. 7,2). Después de 3 meses de seguimiento, ambos grupos mostraron mejoría en todos los parámetros sin haber diferencias estadísticamente significativas. Conclusiones: APC y HOT fueron efectivos, seguros y disminuyeron la toxicidad tisular en los pacientes con PPR. Sin embargo la respuesta fue más efectiva y rápida en el grupo del APC(AU)

Background: chronic radiation proctopathy (CRP) is associated with recurrent rectal bleeding and transfusional requirements. Argon plasma coagulation (APC) and hyperbaric oxygen therapy (HOT) have been shown to be effective in the control of CRP. No prospective comparisons have been reported between these treatments. Aim: the aim was to evaluate the effectiveness, safety and impact on tissue toxicity of APC compared to HOT in patients with CRP. Material and methods: a prospective study for evaluating treatment response was conducted. Patients with cervical cancer and CRP with rectal bleeding were recruited. They had not received previous treatment. Collected data included: demographics, previous radiation dosage, duration and severity of rectal bleeding. Hemoglobin, transfusional requirements, and tissue toxicity (SOMA LENT questionnaire) at baseline and at 1, 2, and 3 months follow up were recorded. Results: thirty-one patients were included, 14 in the APC group and 17 in the HOT group. No response was noted in 13 and 18% of patients in the APC and HOT group respectively (p = NS). At the 1 and 2 months follow-up, the APC group showed a significantly better response in terms of transfusional requirements (0.6 vs. 3.4 and 0.7 vs. 2.5) and tissue toxicity score (5.3 vs. 8.6 and 3.8 vs. 7.248). After 3 months, both groups showed further improvement in all parameters without significant differences between them. Conclusions: APC and HOT were effective, safe and decreased the tissue toxicity scores in patients with CRP. However, response rate was higher and faster in the APC group(AU)

Estudio preliminar de incidencia de hemoglobinopatías, en neonatos tamizados en el Hospital del Niño de Panamá. Agosto-diciembre 2009

Objetivo : Determinar la incidencia de hemoglobinopatías en recién nacidos tamizados en el Hospital del Niño de Panamá de agosto a diciembre 2009. Material y métodos : Realizamos evaluación retrospectiva de los resultados de la prueba de tamiz neonatal 8,620 de sexo masculino y femenino, que fueron tamizados para detección de hemoglobinopatías entre agosto y diciembre de 2009. Resultados: Se revisó en la base de datos del Programa de tamizaje Neonatal del Hospital del Niño, toda la información demográfica y los resultados de tamizaje neonatal para hemoglobinopatías; encontrando en 8,620 recién nacidos tamizados, 4,396 (51%) varones y 4,224 (49%) niñas. Se detectaron 591 (6.8%) hemoglobinopatías anormales con la siguiente distribución : 7 recién nacidos con HbFS (0.08%), 4 Hb FSC (0.05%) , 470 Hb FAS (5,4%), 89 con Hb C (1%), 19 con Hb FAB (0.1%), 1 con Hb FAD, y 1 con HbF. Conclusión: No podemos extrapolar los resultados obtenidos en este estudio preliminar de incidencia de hemoglobinopatías a la incidencia real de nuestra población , porque el porcentaje de cobertura es pequeño y además no contempla recién nacidos de tres regiones de salud con mayor población africana. Sin embargo, si consideramos que los resultados obtenidos en esta investigación son indicativos de que las hemoglobinopatías anormales todavía constituyen un problema de salud pública en Panamá.

Objective: To determine the incidence of hemoglobinopathies in newborns screened at the Hospital del Niño of Panama from August to December 2009. Material and methods: We retrospectively evaluate of the results of neonatal test newborns 8,620 male and female, who were screened for detection of hemoglobinopathies between August and December 2009. Results: We reviewed the database of Neonatal Screening Program at Hospital del Niño, finding in 8,620 screened newborns , 4,396 (51%) were males and 4,224 (49%) girls. Detected 591 (6.8%) abnormal hemoglobins with the following distribution: 7 newborns with HbFS (0.08%), 4 Hb FSC (0.05%), 470 Hb FAS (5.4%), 89 with Hb C , 19 with Hb FAB (0.1%), 1 with Hb FAD, and 1 with HbF. Conclusion: We can´t extrapolate results from this preliminary study to real incidence in our population, mainly because the coverage percentage is small and not include the newborns of these three health regions with significant African ascendance.However, if we take in account results from this research indicate that abnormal hemoglobinopathies still area a public health trouble in Panama.

Cyclin D1 positive diffuse large B-cell lymphoma is a post-germinal center-type lymphoma without alterations in the CCND1 gene locus.

The aims of this study were to analyze the incidence and morphology of cyclin D1+ DLBCL and cases of Richter transformation (RT), and to elucidate possible molecular mechanisms of cyclin D1 overexpression. Seventy-two cases of de novo DLBCL and 12 cases of RT were included in this study. Cyclin D1 positivity was found in 10/66 (15%) cases of unselected de novo DLBCL and in 2/11 (18%) cases of RT. Seven independently identified cases of cyclin D1+ DLBCL, including one RT, were added to the study. Centroblastic morphology was found in 17/19 (89%) cases of cyclin D1+, most with a post-germinal center phenotype (CD10-, BCL6+, MUM1+). No alterations in the CCND1 gene indicative for a translocation t(11;14) were identified by FISH. Analysis of the MYC locus yielded gene copy alterations in five cases and no disruption of the gene locus in any case, suggesting an alternative mechanism of cyclin D1 deregulation.

Granulocytic sarcoma of the breast without development of bone marrow involvement: a case report.

A 29-year-old woman presented with a breast tumor with a primary diagnosis of MALT lymphoma. A repeat biopsy revealed a hematological neoplasm with diffuse, Indian file, and targetoid patterns. The cells were intermediate size with eosinophilic granules; the immunophenotyping showed monocytic differentiation, and no lymphoepithelial lesion was observed. The diagnosis was granulocytic sarcoma. Three different bone marrow biopsies were negative for neoplastic infiltration. After treatment, she developed secondary pancytopenia which contributed to her death 16 months after primary diagnosis. Granulocytic sarcoma of the breast is uncommon. A complete panel of immunohistochemistry is necessary to perform this diagnosis.

Pleomorphic leiomyosarcoma of the adrenal gland with osteoclast-like giant cells.

Pleomorphic leiomyosarcoma (PLMS) of the adrenal gland is a rare tumor in an unusual location. A primary PLMS of the left adrenal gland is reported in a 59-yr-old Mexican woman who presented progressive flank pain and weight loss. The tumor measured 16 cm in diameter, showed markedly pleomorphic and osteoclast-like giant cells, necrosis, and high mitotic activity (average 15 per 10 high-power fields). The phenotype was supported by light microscopy and corroborated by immunohistochemistry. The neoplastic cells were strongly positive for muscle-specific actin, desmin, vimentin, and p53. They were negative for CD34, HMB45, estrogen receptors, and S-100 protein. The percentage of Ki-67 positive neoplastic cells was 7.6%. DNA content analysis by flow cytometry showed that tumor was diploid, with a high level of apoptosis. Extra-adrenal primary sites of origin were clinically excluded. The patient developed local recurrence and liver metastases 12 mo after initial treatment. She then received adjuvant chemotherapy and radiotherapy and the metastasis was resected. Twenty-four months later, she is alive with no evidence of disease. This is the second case of adrenal PLMS reported. This case exhibited a high histologic grade, aggressive behavior, and p53 overexpression, but diploid DNA content.

HER2 expression in cervical cancer as a potential therapeutic target.

BACKGROUND: Trastuzumab, a humanized monoclonal antibody against the HER2 receptor is currently being used in breast and other tumor types. Early studies have shown that a variable proportion of cervical carcinoma tumors overexpress the HER2 receptor as evaluated by diverse techniques and antibodies. Currently it is known that a tumor response to trastuzumab strongly correlates with the level of HER2 expression evaluated by the Hercep Test, thus, it seems desirable to evaluate the status of expression of this receptor using the FDA-approved Hercep Test and grading system to gain insight in the feasibility of using trastuzumab in cervical cancer patients. METHODS: We analyzed a series of cervical cancer cell lines, the primary tumors of 35 cases of cervical cancer patients and four recurrent cases, with the Hercep Test in order to establish whether this tumor type overexpress HER2 at level of 2+/3+ as trastuzumab is currently approved for breast cancer having such level of expression. RESULTS: The results indicate that only 1 out of 35 primary tumors cases overexpress the receptor at this level, however, two out of four recurrent tumors that tested negative at diagnosis shifted to Hercep Test 2+ and 3+ respectively. CONCLUSIONS: The low frequency of expression in primary cases suggests that trastuzumab could have a limited value for the primary management of cervical cancer patients, however, the finding of "conversion" to Hercep Test 2+ and 3+ of recurrent tumors indicates the need to further evaluate the expression of HER2 in the metastatic and recurrent cases.

CYP2C19- and CYP3A4-dependent omeprazole metabolism in West Mexicans.

Omeprazole has been used as a drug probe for CYP2C19, but no systematic data are available for Mexican populations. The aim of this study was to evaluate the phenotype frequencies of the CYP2C19 polymorphism in West Mexicans. Besides omeprazole, sulfone was measured to evaluate CYP3A4 after administration of the 20-mg dose to 127 healthy volunteers. Logarithms of metabolic indexes of omeprazole/hydroxyomeprazole for CYP2C19 and omeprazole/omeprazole sulfone for CYP3A4 had trimodal distributions. Five subjects (4%) had a log CYP2C19 metabolic index below -0.9, suggesting an ultra-extensive phenotype. Poor metabolizers (log metabolic index > 0.6) were 6%. For CYP3A4, 11 subjects (9%) were below -0.3 of the log metabolic index. The log metabolic index of omeprazole/omeprazole sulfone was above the antimode of 0.6 for 11% of this population. The mean log metabolic index of CYP3A4 extensive metabolizers (80%) was 0.166, which seems to be higher than the data described for Caucasians and lower than that for Asians.

Phenotype of CYP2C19 and CYP3A4 by determination of omeprazole and its two main metabolites in plasma using liquid chromatography with liquid-liquid extraction.

We present a new simple and reliable HPLC method for measuring omeprazole and its two main metabolites in plasma. This can be used for studying CYP2C19 and CYP3A4 genetic polymorphisms using omeprazole as the probe drug. Omeprazole, hydroxyomeprazole and omeprazole sulfone were extracted from plasma samples with phosphate buffer and dichloromethane-ether (95:5). HPLC separation was achieved using an Ultrasphere ODS C(18) (Beckman) column. The mobile phase was acetonitrile-phosphate buffer (24:76, pH 8), containing nonylamine at 0.015%. Retention times were 9.5 min for omeprazole, 3.25 min for hydroxyomeprazole, 7.4 min for omeprazole sulfone and 6.27 min for internal standard (phenacetine). Detection (UV at 302 nm) of analytes was linear in the range from 96 to 864 ng/ml. This is useful for calculating metabolic index for CYP2C19 and CYP3A4 in adults and children. This method is stable, reproducible, improves resolution and has practical advantages such as low cost.