Mitochondrial dysfunction in iPSC-derived neurons of subjects with chronic mountain sickness.

Patients with chronic mountain sickness (CMS) suffer from hypoxemia, erythrocytosis, and numerous neurologic deficits. Here we used induced pluripotent stem cell (iPSC)-derived neurons from both CMS and non-CMS subjects to study CMS neuropathology. Using transmission electron microscopy, we report that CMS neurons have a decreased mitochondrial volume density, length, and less cristae membrane surface area. Real-time PCR confirmed a decreased mitochondrial fusion gene optic atrophy 1 (OPA1) expression. Immunoblot analysis showed an accumulation of the short isoform of OPA1 (S-OPA1) in CMS neurons, which have reduced ATP levels under normoxia and increased lactate dehydrogenase (LDH) release and caspase 3 activation after hypoxia. Improving the balance between the long isoform of OPA1 and S-OPA1 in CMS neurons increased the ATP levels and attenuated LDH release under hypoxia. Our data provide initial evidence for altered mitochondrial morphology and function in CMS neurons, and reveal increased cell death under hypoxia due in part to altered mitochondrial dynamics. NEW & NOTEWORTHY Induced pluripotent stem cell-derived neurons from chronic mountain sickness (CMS) subjects have altered mitochondrial morphology and dynamics, and increased sensitivity to hypoxic stress. Modification of OPA1 can attenuate cell death after hypoxic treatment, providing evidence that altered mitochondrial dynamics play an important role in increased vulnerability under stress in CMS neurons.

Reference values for oxygen saturation from sea level to the highest human habitation in the Andes in acclimatised persons.

Oxygen saturation, measured by pulse oximetry (SpO2), is a vital clinical measure. Our descriptive, cross-sectional study describes SpO2 measurements from 6289 healthy subjects from age 1 to 80 years at 15 locations from sea level up to the highest permanent human habitation. Oxygen saturation measurements are illustrated as percentiles. As altitude increased, SpO2 decreased, especially at altitudes above 2500 m. The increase in altitude had a significant impact on SpO2 measurements for all age groups. Our data provide a reference range for expected SpO2 measurements in people from 1 to 80 years from sea level to the highest city in the world.

Acetazolamide and N-acetylcysteine in the treatment of chronic mountain sickness (Monge's disease).

Patients suffering from chronic mountain sickness (CMS) have excessive erythrocytosis. Low -level cobalt toxicity as a likely contributor has been demonstrated in some subjects. We performed a randomized, placebo controlled clinical trial in Cerro de Pasco, Peru (4380m), where 84 participants with a hematocrit (HCT) ≥65% and CMS score>6, were assigned to four treatment groups of placebo, acetazolamide (ACZ, which stimulates respiration), N-acetylcysteine (NAC, an antioxidant that chelates cobalt) and combination of ACZ and NAC for 6 weeks. The primary outcome was change in hematocrit and secondary outcomes were changes in PaO2, PaCO2, CMS score, and serum and urine cobalt concentrations. The mean (±SD) hematocrit, CMS score and serum cobalt concentrations were 69±4%, 9.8±2.4 and 0.24±0.15µg/l, respectively for the 66 participants. The ACZ arm had a relative reduction in HCT of 6.6% vs. 2.7% (p=0.048) and the CMS score fell by 34.9% vs. 14.8% (p=0.014) compared to placebo, while the reduction in PaCO2 was 10.5% vs. an increase of 0.6% (p=0.003), with a relative increase in PaO2 of 13.6% vs. 3.0%. NAC reduced CMS score compared to placebo (relative reduction of 34.0% vs. 14.8%, p=0.017), while changes in other parameters failed to reach statistical significance. The combination of ACZ and NAC was no better than ACZ alone. No changes in serum and urine cobalt concentrations were seen within any treatment arms. ACZ reduced polycythemia and CMS score, while NAC improved CMS score without significantly lowering hematocrit. Only a small proportion of subjects had cobalt toxicity, which may relate to the closing of contaminated water sources and several other environmental protection measures.

SENP1, but not fetal hemoglobin, differentiates Andean highlanders with chronic mountain sickness from healthy individuals among Andean highlanders.

Chronic mountain sickness (CMS) results from chronic hypoxia. It is unclear why certain highlanders develop CMS. We hypothesized that modest increases in fetal hemoglobin (HbF) are associated with lower CMS severity. In this cross-sectional study, we found that HbF levels were normal (median = 0.4%) in all 153 adult Andean natives in Cerro de Pasco, Peru. Compared with healthy adults, the borderline elevated hemoglobin group frequently had symptoms (headaches, tinnitus, cyanosis, dilatation of veins) of CMS. Although the mean hemoglobin level differed between the healthy (17.1 g/dL) and CMS (22.3 g/dL) groups, mean plasma erythropoietin (EPO) levels were similar (healthy, 17.7 mIU/mL; CMS, 12.02 mIU/mL). Sanger sequencing determined that single-nucleotide polymorphisms in endothelial PAS domain 1 (EPAS1) and egl nine homolog 1 (EGLN1), associated with lower hemoglobin in Tibetans, were not identified in Andeans. Sanger sequencing of sentrin-specific protease 1 (SENP1) and acidic nuclear phosphoprotein 32 family, member D (ANP32D), in healthy and CMS individuals revealed that non-G/G genotypes were associated with higher CMS scores. No JAK2 V617F mutation was detected in CMS individuals. Thus, HbF and other classic erythropoietic parameters did not differ between healthy and CMS individuals. However, the non-G/G genotypes of SENP1 appeared to differentiate individuals with CMS from healthy Andean highlanders.

Giant insulinoma: a report of 3 cases and review of the literature.

Insulinoma is a rare pancreatic neuroendocrine tumor that is usually described as benign, sporadic, and very small (<2 cm). However, there have been rare case reports of insulinoma presenting as a giant tumor. We describe 3 cases of giant insulinomas, all of which developed liver metastases. The patients were aged 38, 63, and 67 years. Clinically, all patients presented with Whipple's triad associated with a large mass located in the pancreatic tail. The tumors ranged in size from 10 to 15 cm. On microscopic examination, the tumors were well differentiated with amyloid deposition ranging between 20% and 30%. Immunohistochemically, all 3 tumors showed strong diffuse expression of chromogranin and synaptophysin, whereas they were only focally positive for insulin. One patient developed liver recurrence 3 years after resection of the primary tumor yet remained asymptomatic without treatment. Another patient with liver recurrence underwent right hepatectomy and has been free of disease for 2 years. The third patient died of metastatic disease 13 years after initial surgery. Giant insulinomas are characterized by focal expression of insulin and high rates of liver metastases. Long-term follow-up is mandatory in these patients, as recurrence is expected after primary surgery.

[Impact of duodenopancreatectomy in elder patients]. / Impacto de la duodenopancreatectomía en los pacientes adultos mayores.

UNLABELLED: The incidence of periampullary neoplasms substantially increases with age. If we take into account that this incidence is higher in the elder patient and that life expectancy is nowadays longer, questioning surgical approach in this group of patients turns out to be controversial. OBJECTIVE: [corrected] Asses if in the elder patients the duodenopancreatectomy has a higher mortality and complications. MATERIALS AND METHODS: A retrospective study including patients who underwent duodenopancreatectomy between October 2002 and June 2012 was undertaken to assess whether the elder ones had a higher morbidity and mortality after surgery. Patients were distributed in two groups according to age. The first group included 240 patients younger than 75 years, and the second one included 74 patients older than 75 years. There wasn't NO significant difference in morbidity between the two groups. RESULTS: General mortality for the whole series was 4%. The first group had a 2.9% mortality whereas in the second one mortality reached 4.9%, a significant difference. However, when we changed the reference age from 75 years to 65 or 70 years the difference was not significant any more. CONCLUSION: From this study we can ascertain that an age more than 75 years significantly increases the mortality risk in duodenopancreatectomy patients. This age, however, doesn't proscribe surgical approach, since surgery is the only choice for curative treatment in patients with this type of cancer.

Medication possession ratio predicts antiretroviral regimens persistence in Peru.

OBJECTIVES: In developing nations, the use of operational parameters (OPs) in the prediction of clinical care represents a missed opportunity to enhance the care process. We modeled the impact of multiple measurements of antiretroviral treatment (ART) adherence on antiretroviral treatment outcomes in Peru. DESIGN AND METHODS: Retrospective cohort study including ART naïve, non-pregnant, adults initiating therapy at Hospital Nacional Cayetano Heredia, Lima-Peru (2006-2010). Three OPs were defined: 1) Medication possession ratio (MPR): days with antiretrovirals dispensed/days on first-line therapy; 2) Laboratory monitory constancy (LMC): proportion of 6 months intervals with ≥1 viral load or CD4 reported; 3) Clinic visit constancy (CVC): proportion of 6 months intervals with ≥1 clinic visit. Three multi-variable Cox proportional hazard (PH) models (one per OP) were fit for (1) time of first-line ART persistence and (2) time to second-line virologic failure. All models were adjusted for socio-demographic, clinical and laboratory variables. RESULTS: 856 patients were included in first-line persistence analyses, median age was 35.6 years [29.4-42.9] and most were male (624; 73%). In multivariable PH models, MPR (per 10% increase HR=0.66; 95%CI=0.61-0.71) and LMC (per 10% increase 0.83; 0.71-0.96) were associated with prolonged time on first-line therapies. Among 79 individuals included in time to second-line virologic failure analyses, MPR was the only OP independently associated with prolonged time to second-line virologic failure (per 10% increase 0.88; 0.77-0.99). CONCLUSIONS: The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes.

Whole-genome sequencing uncovers the genetic basis of chronic mountain sickness in Andean highlanders.

The hypoxic conditions at high altitudes present a challenge for survival, causing pressure for adaptation. Interestingly, many high-altitude denizens (particularly in the Andes) are maladapted, with a condition known as chronic mountain sickness (CMS) or Monge disease. To decode the genetic basis of this disease, we sequenced and compared the whole genomes of 20 Andean subjects (10 with CMS and 10 without). We discovered 11 regions genome-wide with significant differences in haplotype frequencies consistent with selective sweeps. In these regions, two genes (an erythropoiesis regulator, SENP1, and an oncogene, ANP32D) had a higher transcriptional response to hypoxia in individuals with CMS relative to those without. We further found that downregulating the orthologs of these genes in flies dramatically enhanced survival rates under hypoxia, demonstrating that suppression of SENP1 and ANP32D plays an essential role in hypoxia tolerance. Our study provides an unbiased framework to identify and validate the genetic basis of adaptation to high altitudes and identifies potentially targetable mechanisms for CMS treatment.

Changes in tuberculin skin test positivity over 20 years in periurban shantytowns in Lima, Peru.

A cross-sectional, community-based study was performed in 2012 with 428 residents of periurban shantytowns in Lima, Peru to study risk factors for and changes in latent tuberculosis infection in age-stratified groups compared with our data from the same region in 1990 (N = 219) and 2005 (N = 103). Tuberculin skin test positivity in these communities was highly prevalent at 52% overall, increased with age (P < 0.01) and was similar to 2005 (53%) and 1990 (48%). From 1990 to 2012, the prevalence of tuberculin positivity decreased in 5-14 and 15-24 year old groups (to 17% and 34%, respectively, both P < 0.05). However, this may be explained by cessation of Bacille Calmette-Guérin revaccination during this period, because Bacille Calmette-Guérin revaccination doubled tuberculin positivity. Over the same 22-year period, tuberculin positivity in the ≥ 25 year old group remained high (71%, P = 0.3), suggesting that prevalent latent tuberculosis infection persists in the adult population despite improving medical care and socioeconomic development in this region.

Impacto de la duodenopancreatectomía en los pacientes adultos mayores / Impact of duodenopancreatectomy in elder patients

La incidencia de las neoplasias peri ampulares se incrementa sustancialmente con la edad, teniendo en cuenta que la incidencia de estas neoplasias se presenta mucho más en pacientes mayores y que la expectativa de vida cada vez es más alta es muy difícil cuestionar la cirugía en este grupo de pacientes. Objetivo: Evaluar la conveniencia de realizar una duodenopancreatectomía en los pacientes adultos mayores y si ésta presenta mayores complicaciones y mortalidad en este grupo de pacientes. Materiales y métodos: Durante el periodo comprendido entre octubre del 2002 hasta junio del 2012 se realizó un estudio retrospectivo en 314 pacientes sometidos a una duodenopancreatectomía para evaluar si los pacientes ancianos presentaban una mayor morbilidad y mortalidad luego de esta cirugía. Se distribuyó a los pacientes en dos grupos de acuerdo a la edad. En el primero se incluyeron a 240 pacientes que eran menores de 75 años y en el segundo se incluyeron a 74 pacientes mayores de 75 años. No existió diferencia significativa en la morbilidad de los dos grupos. Resultados: La mortalidad general en toda la serie fue de 4%. En el primer grupo la mortalidad fue de 2,9% mientras que en el segundo grupo subió a 9,4% ,siendo esta diferencia significativa. Sin embargo, cuando redujimos la edad de comparación a 65 años y a 70 años pudimos comprobar que la diferencia ya no fue significativa. Conclusion: Luego de este estudio podemos afirmar que la edad mayor de 75 años aumenta el riesgo de mortalidad de manera significativa en los pacientes sometidos a una duodenopancreatectomía, pero no contraindica la cirugía ya que es la única opción para tratar de curar a una paciente con este tipo de cáncer.

The incidence of periampullary neoplasms substantially increases with age. If we take into account that this incidence is higher in the elder patient and that life expectancy is nowadays longer, questioning surgical approach in this group of patients turns out to be controversial. Objetive: Asses if in the elder patients the duodenopancreatectomy has a higher mortality and complications. Materials and methods: A retrospective study including patients who underwent duodenopancreatectomy between October 2002 and June 2012 was undertaken to assess whether the elder ones had a higher morbidity and mortality after surgery. Patients were distributed in two groups according to age. The first group included 240 patients younger than 75 years, and the second one included 74 patients older than 75 years. There wasn't NO significant difference in morbidity between the two groups. Results: General mortality for the whole series was 4%. The first group had a 2.9% mortality whereas in the second one mortality reached 4.9%, a significant difference. However, when we changed the reference age from 75 years to 65 or 70 years the difference was not significant any more. Conclusion: From this study we can ascertain that an age more than 75 years significantly increases the mortality risk in duodenopancreatectomy patients. This age, however, doesn't proscribe surgical approach, since surgery is the only choice for curative treatment in patients with this type of cancer.

[Factors associated to complications of endoscopic retrograde cholangiopancreatography in a third-level hospital]. / Factores asociados a complicaciones de la colangiopancreatografía retrógrada endoscópica en un hospital de alta complejidad.

UNLABELLED: Endoscopic treatment of the bile duct diseases is possible thanks to the ERCP (endoscopic retrograde cholangio pancreatography), nevertheless, it is not free of complications. OBJECTIVES: To describe the characteristics and indications of the ERCP and determine the factors associated to the development of complications after performing the procedure. MATERIALS AND METHODS: An observational retrospective study was done in the Gastroenterology Department of the Hospital Guillermo Almenara Irigoyen in Lima, Peru, from March 2002 to June 2005. RESULTS: 294 registers on 280 patients were evaluated, the median age was 58 and 155 (52.7%) were women, five procedures we done in the intensive care unit (ICU). The most frequent indication was choledochus litiasis in 67.3% cases. 205 (69.7%) procedures were successful, only 33 presented complications. The most frequent complications were acute pancreatitis and hemorrhage, in 16 and 13 patients respectively. There were no cases of perforation or death. Pancreatic duct cannulation more than once was an associated factor (OR=2.01; 95%CI: 1.11-5.92; p=0.03). CONCLUSIONS: 11.2% of cases presented complications, being acute pancreatitis and mild hemorrhage the most frequent complications. Only pancreatic duct cannulation more than once is an associated factor for having complications.

Factores asociados a complicaciones de la colangiopancreatografía retrógrada endoscópica en un hospital de alta complejidad / Factors associated to complications of endoscopic retrograde cholangiopancreatography in a third-level hospital

El tratamiento endoscópico de las enfermedades de la vía biliar es posible gracias a la colangiopancreatografía retrógrada endoscópica (CPRE); no obstante, no está exenta de complicaciones. Objetivos. Describir las características e indicaciones de la CPRE y determinar los factores asociados al desarrollo de complicaciones tras la realización de este procedimiento. Materiales y métodos. Se realizó un estudio observacional retrospectivo en el Departamento de Gastroenterología del Hospital Nacional Guillermo Almenara Irigoyen en Lima, Perú; desde marzo de 2002 a junio de 2005. Resultados. Se evaluaron 294 informes en 280 pacientes, la mediana de la edad fue 58 y 155 (52,7%) fueron mujeres; cinco procedimientos se efectuaron en la Unidad de Cuidados Intensivos (UCI). La indicación más frecuente fue la coledocolitiasis en el 67,3% de los casos, 205 (69,7%) procedimientos fueron exitosos complicándose sólo 33 de ellos. Las complicaciones más frecuentes fueron la pancreatitis aguda y la hemorragia, en 16 y 13 pacientes, respectivamente. No se reportó casos de perforación o defunción. La canulación del conducto pancreático más de una vez fue un factor asociado (OR=2,01; IC95%: 1,11 - 5,92; p=0,03). Conclusiones. El 11,2% de los casos se complicaron, siendo la pancreatitis aguda y la hemorragia leve las complicaciones más frecuentes. Sólo la canulación al conducto pancreático en más de una oportunidad es un factor asociado para tener complicaciones.

Endoscopic treatment of the bile duct diseases is possible thanks to the ERCP (endoscopic retrograde cholangiopancreatography), nevertheless, it is not free of complications. Objectives. To describe the characteristics and indications of the ERCP and determine the factors associated to the development of complications after performing the procedure. Materials and methods. An observational retrospective study was done in the Gastroenterology Department of the Hospital Guillermo Almenara Irigoyen in Lima, Peru, from March 2002 to June 2005. Results. 294 registers on 280 patients were evaluated, the median age was 58 and 155 (52.7%) were women, five procedures we done in the intensivecare unit (ICU). The most frequent indication was choledochus litiasis in 67.3% cases. 205 (69.7%) procedures were successful, only 33 presented complications. The most frequent complications were acute pancreatitis and hemorrhage, in 16 and 13 patients respectively. There were no cases of perforation or death. Pancreatic duct cannulation more than once was an associated factor (OR=2.01; 95% CI: 1.11-5.92; p=0.03). Conclusions. 11.2% of cases presented complications, being acute pancreatitis and mild hemorrhage the most frequent complications. Only pancreatic duct cannulation more than once is an associated factor for having complications.

[Cytotoxic effect of physalis peruviana in cell culture of colorectal and prostate cancer and chronic myeloid leukemia]. / Actividad citotoxica de physalis peruviana (aguaymanto) en cultivos celulares deadenocarcinoma colorectal, prostata y leucemia mieloide cronica.

INTRODUCTION: The plants have been used as drugs for centuries. However, limited research has been done on its great potential as sources of new therapeutic agents. The purpose of this study was to evaluate Physalis peruviana cytotoxic activity on cell lines HT-29, PC-3, K-562 and VERO. MATERIALS AND METHODS: The HT-29 cell lines, PC-3, K-562 and VERO, were exposed to four concentrations of P. peruviana ethanolic leave and stem extracts, also at different concentrations of cisplatin and 5-fluorouracil (5-FU), which were used as positive controls. We found rates of growth within 48 hours, then we determined the inhibitory concentration 50 (IC50) using linear regression analysis and the index of selectivity of each sample. RESULTS: The P. peruviana ethanolic leave and stem extracts showed cytotoxic activity. The IC50 in g/mL in leaves and stems were, 0.35 (r =-0.95 p <0.025) and 0.37 (r =- 0.90 p <0.05 ) for HT-29; 0.87 (r =-0.98 p <0.01) and 1.01 (r =-0.95 p <0.025) for PC-3; 0.02 (r =-0.98 p <0.01) and 0.03 (r =-0.98 p <0.01) for K-562; 4.9 (r =-0.95 p <0.025) and 6.2 (r =-0.98 p <0.01) for VERO. The IC50 for antineoplastic were: for cisplatin: 4.2 (r =-0.96 p <0.025), 10.3 (r =-0.97 p <0.025), 0.15 (r =-0.98 p = 0.01) and 1.1 (r =- 0.98 p = 0.01); for 5-FU: 2.3 (r =-0.97 p <0.025), 17.9 (r =-0.95 p <0.025), 0.15 (r =-0.98 p = 0.01) and 1.1 (r =-0.94 p = 0.05) for HT-29, PC-3, K562 and VERO respectively. The leaves and stems extracts selectivity index were between 5.6 and 245 for tumor cell lines evaluated, by contrast, cisplatin and 5-FU, only showed values between 0.11 and 7.3. CONCLUSIONS: The P. peruviana leaves and steams ethanolic extracts were more cytotoxic than cisplatin and 5 FU, on the lines HT-29, PC-3 and K562. Furthermore the P. peruviana cytotoxic effects were less than cisplatin and 5-FU for VERO control cells lines.

Actividad citotóxica de physalis peruviana (aguaymanto) en cultivos celulares de adenocarcinoma colorectal, próstata y leucemia mieloide crónica / Cytotoxic effect of physalis peruviana in cell culture of colorectal and prostate cancer and chronic myeloid leukemia

INTRODUCCIÓN: Las plantas han sido empleadas como drogas por siglos. Sin embargo, se ha investigado poco sobre su gran potencial como fuentes de nuevos agentes terapéuticos. El objetivo del presente trabajo fue evaluar la actividad citotóxica de los extractos etanólicos de tallos y hojas de Physalis peruviana, sobre las líneas celulares HT-29, PC-3, K-562 y VERO. MATERIALES Y MÉTODOS: Las líneas celulares HT-29, PC-3, K-562 y VERO, fueron expuestas a cuatro concentraciones de extractos etanólicos de tallos y hojas de Physalis peruviana. Asimismo, a diferentes concentraciones de cisplatino y 5-Fluorouracilo (5-FU), que se usaron como controles positivos. Se hallaron los porcentajes de crecimiento en 48 horas, luego se determinó la concentración inhibitoria 50 (IC50) mediante análisis de regresión lineal y el índice de selectividad de cada muestra. RESULTADOS: Los extractos etanólicos de tallos y hojas de Physalis peruviana mostraron actividad citotóxica: Los CI50 en μg/mL en hojas y tallos fueron, 0.35 (r=-0.95 p<0.025) y 0.37 (r=-0,90 p<0.05) para HT-29; 0.87 (r=-0.98 p<0.01) y 1.01 (r=-0.95 p<0.025) para PC-3; 0.02 (r=-0.98 p<0.01) y 0.03 (r=-0.98 p<0.01) para K-562; 4.9 (r=-0.95 p<0.025) y 6.2 (r=-0.98 p<0.01) para VERO. Los CI50 para los antineoplásicos fueron: para el cisplatino: 4.2 (r=-0.96 p<0.025), 10.3 (r=-0.97 p<0.025), 0.15 (r=-0.98 p=0.01), y 1.1 (r=-0.98 p=0.01). Parael 5-FU: 2.3 (r=-0.97 p<0.025), 17.9 (r=-0.95 p<0.025), 0.15 (r=-0.98 p=0.01), y 1.1 (r=-0.94 p=0.05) para HT-29, PC-3, K562 y VERO, respectivamente. Los índices de selectividad de los extractos de tallos y hojas, estuvieron entre 5.6 y 245 para las líneas celulares tumorales evaluadas; por el contrario, el cisplatino y el 5-FU, solo alcanzaron valores entre 0.11 y 7.3...

INTRODUCTION: The plants have been used as drugs for centuries. However, limited research has been done on its great potential as sources of new therapeutic agents. The purpose of this study was to evaluate Physalis peruviana cytotoxic activity on cell lines HT-29, PC-3, K-562 and VERO. Materials and Methods: The HT-29 cell lines, PC-3, K-562 and VERO, were exposed to four concentrations of P. peruviana ethanolic leave and stem extracts, also at different concentrations of cisplatin and 5-fluorouracil (5-FU), which were used as positive controls. We found rates of growth within 48 hours, then we determined the inhibitory concentration 50 (IC50) using linear regression analysis and the index of selectivity of each sample. RESULTS: The P. peruviana ethanolic leave and stem extracts showed cytotoxic activity. The IC50 in μg/mL in leaves and stems were, 0.35 (r =-0.95 p <0.025) and 0.37 (r =- 0.90 p <0.05 ) for HT-29; 0.87 (r =-0.98 p <0.01) and 1.01 (r =-0.95 p <0.025) for PC-3; 0.02 (r =-0.98p <0.01) and 0.03 (r =-0.98 p <0.01) for K-562; 4.9 (r =-0.95 p <0.025) and 6.2 (r =-0.98 p <0.01) for VERO. The IC50 for antineoplastic were: for cisplatin: 4.2 (r =-0.96 p <0.025),10.3 (r =-0.97 p <0.025), 0.15 (r =-0.98 p = 0.01) and 1.1 (r =- 0.98 p = 0.01); for 5-FU: 2.3 (r =-0.97 p <0.025), 17.9 (r =-0.95 p <0.025), 0.15 (r =-0.98 p = 0.01) and 1.1 (r =-0.94 p = 0.05) for HT-29, PC-3, K562 and VERO respectively. The leaves and stems extracts selectivity index were between 5.6 and 245 for tumor cell lines evaluated, by contrast, cisplatin and 5-FU, only showed values between 0.11 and 7.3. CONCLUSIONS: The P. peruviana leaves and steams ethanolic extracts were more cytotoxic than cisplatin and 5 FU, on the lines HT-29, PC-3 and K562. Furthermore the P. peruviana cytotoxic effects were less than cisplatin and 5-FU for VERO control cells lines.

Primary squamous cell carcinoma of the stomach with paraneoplastic leukocytosis: a case report and review of literature.

Apparently pure, primary squamous cell carcinoma of the stomach is exceedingly rare. To date, less than 100 cases have been reported. Here, we describe a case of primary squamous cell carcinoma arising in the gastric antrum of an 83-year-old man with persistent leukocytosis, which resolved on resection of the tumor. No foci of squamous metaplasia or gland-forming elements were identified in the resection specimen, although there was marked chronic gastritis with intestinal metaplasia. There was no evidence of Helicobacter, fungal, or parasitic infection. Immunohistochemical and in situ hybridization studies for human papillomavirus and Epstein-Barr virus were negative. This case suggests that gastric squamous cell carcinoma likely arises in the setting of long-standing, chronic inflammation, and like squamous cell carcinoma in other organ systems, may be associated with paraneoplastic leukocytosis.