Impact of single-nucleotide variants and nutritional status on population pharmacokinetics of Doxorubicin, and its effect on cardiotoxicity in children with leukemia.

PURPOSE:  Doxorubicin is an important antineoplastic agent with wide interindividual variability in response to treatment and in its cardiotoxic effects. To determine the effect of genotypic status of three single-nucleotide variants in ABCC1, NCF4, and CBR3 genes and nutritional status assessed by body mass index, on the population pharmacokinetics of Doxorubicin and its cardiotoxic effects in pediatric patients with leukemia. PATIENTS AND METHODS: Seventy pediatric patients treated with Doxorubicin were studied, in which 189 biological samples were obtained to determine Doxorubicin concentrations (1 to 3 samples per patient) at different times, for 20 h. RESULTS: Low body mass index and age ≤ 7 years were associated with decreased clearance of Doxorubicin, and female gender was associated with increased clearance of Doxorubicin. Low BMI and low height were associated with a decrease and increase, respectively, in the intercompartmental clearance (Q) of Doxorubicin. TT homozygosity of the single-nucleotide variant rs3743527 of the ABCC1 gene was associated with an increase in clearance and decreased area under the curve, AA homozygosity of the single-nucleotide variant rs1883112 of the NCF4 gene was associated with a decrease in the volume of distribution in the peripheral compartment (V2), and GG homozygosity of CBR3 rs1056892 with increasing area under the curve. CONCLUSION: Some covariates studied are directly related to the increase or decrease of the pharmacokinetic parameters of Doxorubicin. Decreased clearance, V2, and increased area under the curve were associated with systolic dysfunction, and decreased Q and V2 were associated with diastolic dysfunction. These results may contribute to the effective and safe use of Doxorubicin in pediatric patients with leukemia.

Association of genetic polymorphisms NCF4 rs1883112, CBR3 rs1056892, and ABCC1 rs3743527 with the cardiotoxic effects of doxorubicin in children with acute lymphoblastic leukemia.

OBJECTIVES: Cardiotoxicity is a frequent complication secondary to the use of anthracyclines for cancer chemotherapy. Evidence suggests that certain polymorphic genetic variants modify the risk for anthracycline-related cardiotoxicity. Reports documenting the impact of genetic polymorphisms on anthracycline-cardiotoxicity risk in pediatric patients with cancers from Latin American countries are scarce. The objective of this study was to evaluate associations between NCF4 rs1883112, CBR3 rs1056892 and ABCC1 rs3743527 genotype status and echocardiographic parameters indicative of anthracycline-cardiotoxicity in a group of Mexican children with acute lymphoblastic leukemia (ALL). METHODS: Sixty-seven children (2-18 years old) with ALL were treated at the State Cancer Center in Durango, Mexico. NCF4, CBR3, and ABCC1 genotypes were examined by real-time PCR. Left ventricular ejection fraction and diastolic filling ratio were examined as markers of systolic and diastolic anthracycline-toxicity. RESULTS: NCF4 rs1883112 genotype status was significantly associated with the risk of doxorubicin cardiotoxicity [odds ratio (OR) = 10.80, 95% confidence interval (CI) 1.69-68.98, P = 0.01]. There was a significant association between heterozygous CBR3 rs1056892 genotype status and anthracycline-cardiotoxicity risk (OR = 9.91, 95% CI 1.07-91.47, P = 0.04). Heterozygosis for the ABCC1 rs3743527 allele was associated with protection from anthracycline-cardiotoxicity (OR = 0.30, 95% CI 0.09-0.91, P = 0.03). CONCLUSION: This pilot study suggests that selected polymorphic variants may impact the risk for anthracycline-cardiotoxicity in pediatric patients with ALL treated with a contemporary chemotherapeutic regimen in Mexico.

Genotype Analysis of ABCC1, NCF4 and CBR3 Polymorphism and the Association With Childhood Acute Lymphoblastic Leukemia in Mexican Childhood Population.

Background: The identification of genetic risk factors for Acute Lymphoblastic Leukemia (ALL), are increasingly urgent and necessary. Objective: The purpose of this study is to determine the association of the genetic polymorphisms ABCC1 rs3743527, NCF4 rs1883112 and CBR3 rs1056892 with ALL. Methods: DNA samples were obtained in 71 children with ALL (from 2 to 18 years) and in 71 controls without ALL, to determine the polymorphisms by real-time polymerase chain reaction (qPCR), using specific TaqMan probes in a StepOne® thermal cycler (Applied Biosystems, United States). Results: The results of the Odds Ratio analysis show that in the rs1883112 polymorphism of the NCF4 gene, the heterozygous allele has a risk effect for ALL (OR = 3.1870, CI = 1.8880-7.9383 and p = 0.0002), in turn the mutated genotype (AA) is associated with a protective effect (OR = 0.26, 0.1248 to 0.5434 and p = 0.0003). On the other hand, the CBR3 rs1056892 polymorphism shows a significant association of risk to ALL, in the presence of the HT genotype (OR = 2.77, IC = 1.3837 to 5.5651 and p = 0.004) and the mutated genotype of this polymorphism has a significant association with protection to ALL in the HM genotype (OR = 0.52, IC = 0.2639 to 1.0304 and p = 0.05). While the inheritance models of the polymorphisms let us see that of the rs1883112 polymorphism of the NCF4 polymorphism; the HT genotype of the codominant model shows a protective effect against ALL (OR = 0.4117, IC = 0.1718 to 0.9866 and p = 0.04), the recessive model shows us and confirms what we already saw in table number 3, being that there is an association with protective effect in the HM genotype (OR = 0.2604, IC = 0.1248 to 0.5434 and p = 0.0003). In the polymorphism rs1056892 of the CBR3 gene, a protection association was found in the heterozygous allele of the codominant model (OR = 0.3448, IC = 0.1375 to 0.8896 and p = 0.0274). In addition, the recessive inheritance model for the HM genotype shows a protective effect to ALL, (OR = 0.52, CI = 0.9919 to 3.8638 and p = 0.05). Conclusion: There is an evident impact of the NCF4 rs1883112 and CBR3 rs1056892 polymorphisms with an increased risk of susceptibility to ALL; Likewise, through the codominant inheritance model, the effect of the variation of the CBR3 rs1056892 gene as a protective factor against ALL was evaluated.

Recurrent epibulbar dermoid cyst treated with amniotic membrane implant a case report.

BACKGROUND: The dermoid cyst considered a cystic teratoma derived from embryonic germinal epithelium is a slow-growing benign tumour. Dermoid cysts may occur in the orbital and periorbital region in paediatric patients and are often recurrent. The surgical approach depends upon the site of the lesion, superficial or deep. To our knowledge, this is the first described case of a patient with resection of dermoid cyst treated with human amniotic membrane implant and topical application of 0.02% mitomycin C. CASE PRESENTATION: We present a case of a 12-year-old male with a tumour in the superotemporal region of the right eye (RE). Symptoms included decreased visual acuity (VA), burning eye, foreign body sensation, and photophobia of the affected eye. A physical examination detected blepharospasm. Ophthalmic examination of his RE, fingers count from a 1-2 m distance, showed no improvement with pinhole. Visual acuity was 20/20 on the left eye (LE). The bio-microscopic examination confirmed the presence of a tumour mass (15 mm × 12 mm) on the surface of the RE, invading the superotemporal sector. The tumour had a lobulated appearance, a shiny and vascularized surface covered by conjunctiva, a pearlescent-pink colour, a medium consistency, was renitent and painless. An ultrasound scan revealed atrophy of the pigmented retinal epithelium with scleral indentation of the RE. A computed tomography (CT) scan revealed a recurrent lesion consistent with an epibulbar dermoid cyst. Surgical excision of the lesion was performed and a human amniotic membrane (HAM) graft and topical 0.02% mitomycin C (MMC) were applied. Histopathological analysis confirmed the diagnosis of recurrent dermoid cyst. CONCLUSION: In this case report, we describe a case of recurrent epibulbar dermoid cyst treated with complete resection; topical MMC and HAM implant with good clinical outcome of the lesion and implant adhesion. Resection of a cyst of the ocular surface is not recommended when a large epibulbar dermoid tissue needs to be resected and no HAM graft is available.

Population Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Children Undergoing Ambulatory Surgery.

BACKGROUND: Dexmedetomidine (DEX) is an α-2 adrenergic agonist with sedative and analgesic properties. Although not approved for pediatric use by the Food and Drug Administration, DEX is increasingly used in pediatric anesthesia and critical care. However, very limited information is available regarding the pharmacokinetics of DEX in children. The aim of this study was to investigate DEX pharmacokinetics and pharmacodynamics (PK-PD) in Mexican children 2-18 years of age who were undergoing outpatient surgical procedures. METHODS: Thirty children 2-18 years of age with American Society of Anesthesiologists physical status score of I/II were enrolled in this study. DEX (0.7 µg/kg) was administered as a single-dose intravenous infusion. Venous blood samples were collected, and plasma DEX concentrations were analyzed with a combination of high-performance liquid chromatography and electrospray ionization-tandem mass spectrometry. Population PK-PD models were constructed using the Monolix program. RESULTS: A 2-compartment model adequately described the concentration-time relationship. The parameters were standardized for a body weight of 70 kg by using an allometric model. Population parameters estimates were as follows: mean (between-subject variability): clearance (Cl) (L/h × 70 kg) = 20.8 (27%); central volume of distribution (V1) (L × 70 kg) = 21.9 (20%); peripheral volume of distribution (V2) (L × 70 kg) = 81.2 (21%); and intercompartmental clearance (Q) (L/h × 70 kg) = 75.8 (25%). The PK-PD model predicted a maximum mean arterial blood pressure reduction of 45% with an IC50 of 0.501 ng/ml, and a maximum heart rate reduction of 28.9% with an IC50 of 0.552 ng/ml. CONCLUSIONS: Our results suggest that in Mexican children 2-18 years of age with American Society of Anesthesiologists score of I/II, the DEX dose should be adjusted in accordance with lower DEX clearance.

Farmacogenómica como herramienta fundamental para la medicina personalizada: aplicaciones en la práctica clínica / Clinical applications of pharmacogenomics

Pharmacogenomics is an emergent field aimed at tailoring pharmacological therapy. Genetic polymorphisms can modify the expression and function of enzymes and proteins involved in drug metabolism, affecting absorption, distribution, biotransformation and excretion as well as the drug-target interaction. Therefore, the presence of allelic variants will classify people as poor, extensive or rapid/ultra rapid metabolizers, modifying drug efficacy and safety. In this work, the state of art in relation to this discipline is presented and the genetic variants of enzymes that are involved in drug pharmacokinetics or pharmacodynamics are described. The effects of these variants on the therapeutic response to drugs used in our country are also discussed.

Genetic Polymorphisms Associated to Folate Transport as Predictors of Increased Risk for Acute Lymphoblastic Leukemia in Mexican Children.

Acute lymphoblastic leukemia (ALL) is a frequent neoplasia occurring in children. The most commonly used drug for the treatment of ALL is methotrexate (MTX), an anti-folate agent. Previous studies suggest that folate transporters play a role in ALL prognosis and that genetic polymorphism of genes encoding folate transporters may increase the risk of ALL. Therefore, the main goal of this study was to determine the associations among six genetic polymorphisms in four genes related with the folate transporter pathway to determine a relationship with the occurrence of ALL in Mexican children. A case-control study was performed in 73 ALL children and 133 healthy children from Northern and Northwestern Mexico. COL18A1 (rs2274808), SLC19A1 (rs2838956), ABCB1 (rs1045642 and rs1128503), and ABCC5 (rs9838667 and rs3792585). Polymorphisms were assayed through qPCR. Our results showed an increased ALL risk in children carrying CT genotype (OR = 2.55, CI 95% 1.11-5.83, p = 0.0001) and TT genotype (OR = 21.05, CI 95% 5.62-78.87, p < 0.0001) of COL18A1 rs2274808; in SLC19A1 rs2838956 AG carriers (OR = 44.69, CI 95% 10.42-191.63, p = 0.0001); in ABCB1 rs1045642 TT carriers (OR = 13.76, CI 95% 5.94-31.88, p = 0.0001); in ABCC5 rs9838667 AC carriers (OR = 2.61, CI 95% 1.05-6.48, p < 0.05); and in ABCC5 rs3792585 CC carriers (OR = 9.99, CI 95% 3.19-31.28, p = 0.004). Moreover, several combinations of genetic polymorphisms were found to be significantly associated with a risk for ALL. Finally, two combinations of ABCC5 polymorphisms resulted in protection from this neoplasia. In conclusion, certain genetic polymorphisms related to the folate transport pathway, particularly COL18A1 rs2274808, SLC19A1 rs2838956, ABCB1 rs1045642, and ABCC5 rs3792585, were associated with an increased risk for ALL in Mexican children.

Involvement of MTHFR and TPMT genes in susceptibility to childhood acute lymphoblastic leukemia (ALL) in Mexicans.

BACKGROUND: Folate metabolism plays an essential role in the processes of DNA synthesis and methylation. Deviations in the folate flux resulting from single-nucleotide polymorphisms in genes encoding folate-dependent enzymes may affect the susceptibility to leukemia. This case-control study aimed to assess associations among MTHFR (C677T, A1298C) and TPMT (*2, *3A) mutations as well as to evaluate the synergistic effects of combined genotypes for both genes. Therefore, these genetic variants may lead to childhood acute lymphoblastic leukemia (ALL) susceptibility, in a Mexican population study. METHODS: DNA samples obtained from 70 children with ALL and 152 age-matched controls (range, 1-15 years) were analyzed by real-time reverse transcription polymerase chain reaction (RT-qPCR) to detect MTHFR C677T and A1298C and TPMT*2 and TPMT*3A genotypes. RESULTS: The frequency of the MTHFR A1298C CC genotype was statistically significant (odds ratio [OR], 6.48; 95% 95% confidence intervals [CI], 1.26-33.2; p=0.025). In addition, the combined 677CC+1298AC genotype exhibited a statistically significant result (OR, 0.23; 95% CI, 0.06-0.82; p=0.023). No significant results were obtained from the MTHFR (C677T CT, C677T TT) or TPMT (*2, *3A) genotypes. More importantly, no association between the synergistic effects of either gene (MTHFR and/or TPMT) and susceptibility to ALL was found. CONCLUSIONS: The MTHFR A1298C CC genotype was associated with an increased risk of developing childhood ALL. However, a decreased risk to ALL with the combination of MTHFR 677CC+1298AC genotypes was found.

Association of ABCB1, ABCC5 and xanthine oxidase genetic polymorphisms with methotrexate adverse reactions in Mexican pediatric patients with ALL.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is one of the most frequent oncological disorders in pediatric populations. To date, the drug of choice for the treatment of ALL is methotrexate, a drug associated with a high risk of adverse reactions (ADRs). The xanthine oxidase (XO) polymorphisms, 1936A>G and 2107A>G, as well as the polymorphic variants derived from ATP-binding cassette transporter gene subfamilies, ABCB1 and ABCC5, of drug resistant codifying genes, are implicated as precursors of drug-related neurologic, hepatic, and renal toxicities. Our aim was to determine whether the mentioned polymorphisms are risk or protective factors for the development of adverse reactions by methotrexate in our pediatric population with ALL. METHODS: A total of 35 Mexican children from Centro Estatal de Cancerología-Durango, Mexico, with ALL and the previously noted polymorphisms as determined qPCR were studied. At the same time, a 12-month drug monitoring program was conducted in accordance with WHO-PAHO guidelines for pharmacovigilance. RESULTS: The ABCB11936A>G and 2107A>G and ABCC5 3414+434A>C polymorphisms were not associated with methotrexate ADRs. Single nucleotide polymorphisms (SNPs) of ABCB1 1236C>T (OR 0.19, 95% CI: 0.03-0.9, p<0.05) and ABCC5 3933+313T>C (OR 0.12, 95% CI: 0.027-0.58, p<0.05) were associated with methotrexate ADRs. CONCLUSIONS: SNPs 1236C>T of ABCB1 and ABCC5 3933+313T>C are not associated with the development of typical ADRs by methotrexate, rather, they showed a protective factor for myelosuppression in the studied sick population.

Impacto de polimorfismos genéticos de la vía metabólica del metotrexato sobre la sobrevida de niños mexicanos con leucemia linfoblástica aguda (LLA) / Impact of genetic polymorphism of metabolic pathway of methotrexate and survival rate of mexican children will all

Antecedentes: La leucemia linfoblástica aguda (LLA) es un padecimiento oncológico importante en la población pediátrica mexicana, cuya base genética pudiera modificar la efectividad de la quimioterapia del antifolato metotrexato (MTX) y el tiempo de sobrevida libre de enfermedad y la sobrevida total. Objetivo: Determinar la asociación de 10 polimorfismos genéticos de la vía del folato: en transportadores celulares (COL18A1, SLC19A1, ABCB1 y ABCC5) y las enzimas folilpoliglutamil sintetasa (FPGS) y xantina oxidasa (XO), con la sobrevida de los niños con leucemia linfoblástica aguda. Métodos: En el Centro Estatal de Cancerología de Durango- México, se estudiaron 39 niños con leucemia linfoblástica aguda tratados con MTX y 102 controles sin la enfermedad, a quienes mediante qPCR, se les determinaron 10 polimorfismos en la vía del folato. Durante 5 años de seguimiento se determinó la sobrevida libre de enfermedad y la sobrevida total, y su relación con su genotipo. Resultados: Cuatro polimorfismos no estuvieron en equilibrio de Hardy-Weinberg COL18A1 (rs2274808), ABCC5 (rs9838667 y rs3792585) y XO (rs17011368). Únicamente el rs17011368 de XO se asoció con riesgo de estar presente en los pacientes con leucemia linfoblástica aguda cuyo OR fue 9.771(IC95% 4.974-19.196, p=0,001). El FPGS (rs1544105) afectó la sobrevida libre de enfermedad y la sobrevida total (Log Rank p<0.05). Conclusiones: El polimorfismo (rs17011368) de la XO presentó riesgo para leucemia linfoblástica aguda; así mismo, se encontró una asociación importante entre los portadores del polimorfismo FPGS (rs1544105) que modificaría la sobrevidas de los pacientes tratados con MTX.

Background: Acute lymphoblastic leukemia (ALL) is a major cancer disease in Mexican pediatric population, were the genotype could affect the effectiveness of chemotherapy in which the methotrexate (MTX) is involved and consequently the time of disease free survival and overall survival. Objective: Determine the association of 10 genetic polymorphisms of the folate pathway: in cellular carriers (COL18A1, SLC19A1, ABCB1 and ABCC5) and in enzymes such as folylpolyglutamate synthetase (FPGS) and xanthine oxidase (XO), with survival of children with acute lymphoblastic leukemia. Methods: Thirtynine children with acute lymphoblastic leukemia from the State Cancer Center in Durango (Mexico) treated with MTX and 102 healthy controls, were qPCR analyzed for 10 polymorphisms in the folate pathway. During 5 years of follow up, the disease-free survival and overall survival rates were investigated in relation with their genotypes. Results: Four polymorphisms were not found in Hardy-Weinberg Equilibrium COL18A1 (rs2274808), ABCC5 (rs9838667 and rs3792585) and XO (rs170113685). Only XO (rs170113685) was associated with risk of being present in patients with ALL whose odds ratio was 9.771 (95% 4.974-19.196, p=0.001). The polymorphism rs1544105 for FPGS affected disease free survival and overall survival (Log Rank test p<0.05). Conclusion: Polymorphism (rs17011368) of XO showed risk association for acute lymphoblastic leukemia; likewise, an important association was found between carriers of the FPGS (rs1544105) and increased survival times of patients treated with methotrexate.

Colecistectomía laparoscópica en un paciente con sistema de derivación ventriculoperitoneal / Laparoscopic cholecystectomy in a patient with ventriculoperitoneal shunt system

Introducción: Los pacientes pediátricos con hidrocefalia y sistemas de derivación ventriculoperitoneal (válvula de derivación ventriculoperitoneal [VDVP]) no están exentos de padecer enfermedades gastrointestinales. En la actualidad, con los avances tecnológicos, sería controvertido no ofrecerles los beneficios de la cirugía de mínima invasión. A la fecha no hay estudios comparativos entre las diferentes técnicas que permitan evaluar cuál es la mejor forma de evitar la hipertensión endocraneal. Sin embargo, existen cada vez más reportes de cirugía segura en niños con VDVP operados por laparoscopia. Caso clínico: Se presenta el caso de una colecistectomía laparoscópica en un paciente masculino de 14 años de edad con un sistema de VDVP que presentó datos clínicos de colecistitis. La evolución del paciente fue satisfactoria, y causó alta hospitalaria a las 72 h de la cirugía. Conclusiones: Actualmente son comunes los casos de niños con hidrocefalia y sistemas de VDVP que requieren de alguna cirugía laparoscópica. Esta cirugía resulta segura para diversos procedimientos, incluyendo patología vesicular y de ovario. Los resultados satisfactorios ayudarán al cirujano a tomar una mejor decisión quirúrgica en este tipo de pacientes pediátricos.

Background: Pediatric patients with hydrocephalus and ventriculoperitoneal (VP) shunt systems are not exempt from suffering from gastrointestinal diseases. Today, with technological advances it would be controversial to not offer the benefits of minimally invasive surgery. To date, no studies have been carried out comparing different techniques to assess the best way to prevent intracranial hypertension. However, there are increasing reports of safe surgery in children with VP shunt operated by laparoscopy. Case report: We present the case of a 14-year-old male who presented for laparoscopic cholecystectomy with a VP shunt system. The patient had clinical data of cholecystitis; therefore, it was decided to perform laparoscopic cholecystectomy. The patient experienced a satisfactory evolution with hospital discharge at 72 h postoperatively. Conclusions: Currently, it is common that children with hydrocephalus and VP systems may require some type of laparoscopic surgery. This surgery is safe for various procedures including gallbladder and ovarian pathology. Satisfactory results will help the surgeon make a better surgical decision in this type of pediatric patient.

[Laparoscopic cholecystectomy in a patient with ventriculoperitoneal shunt system]. / Colecistectomía laparoscópica en un paciente con sistema de derivación ventriculoperitoneal.

BACKGROUND: Pediatric patients with hydrocephalus and ventriculoperitoneal (VP) shunt systems are not exempt from suffering from gastrointestinal diseases. Today, with technological advances it would be controversial to not offer the benefits of minimally invasive surgery. To date, no studies have been carried out comparing different techniques to assess the best way to prevent intracranial hypertension. However, there are increasing reports of safe surgery in children with VP shunt operated by laparoscopy. CASE REPORT: We present the case of a 14-year-old male who presented for laparoscopic cholecystectomy with a VP shunt system. The patient had clinical data of cholecystitis; therefore, it was decided to perform laparoscopic cholecystectomy. The patient experienced a satisfactory evolution with hospital discharge at 72h postoperatively. CONCLUSIONS: Currently, it is common that children with hydrocephalus and VP systems may require some type of laparoscopic surgery. This surgery is safe for various procedures including gallbladder and ovarian pathology. Satisfactory results will help the surgeon make a better surgical decision in this type of pediatric patient.

Importancia de la serie esofagogastroduodenal en niños con reflujo gastroesofágico / Importance of upper gastrointestinal series in children with gastroesophageal reflux

La importancia de realizar una serie esofagogastroduodenal (SEGD) en todo paciente con datos de reflujo gastroesofágico (RGE) radica en descartar cualquier anormalidad anatómica que esté condicionando el RGE. De estas anomalías, la más catastrófica es el vólvulo del intestino medio. Ocurre como una complicación en pacientes con malrotación intestinal, y se debe tratar como una urgencia quirúrgica. Por ello, se recomienda realizar la SEGD antes de iniciar un tratamiento médico o quirúrgico en todo paciente con RGE. Los pacientes con malrotación intestinal presentan síntomas como vómitos biliares o gástricos, RGE, náuseas, anorexia, distención abdominal o dolor abdominal crónico intermitente, estreñimiento, diarrea, evacuaciones con sangre y detención del crecimiento. Sin embargo, algunos pacientes presentan solo alguno de estos síntomas o cursan asintomáticos. El 75% de los pacientes con malrotación intestinal presenta RGE o vómito de características biliares, mientras que en el 25% restante, el RGE es de características gastroalimenticias y puede pasar desapercibido. En estos pacientes, la SEGD seguida de tránsito intestinal continúa siendo el estudio de elección para descartar malformaciones u alteraciones anatómicas del tracto digestivo, como la malrotación o vólvulo intestinal.

Midgut volvulus is a surgical emergency and occurs as a complication in patients with malrotation. The importance of an upper gastrointestinal series (UGI) in all patients with gastroesophageal reflux disease (GERD) is to rule out any anatomic abnormality precipitated by GERD. Of these abnormalities, ''midgut volvulus'' is the most catastrophic complication and occurs with intestinal malrotation and should be treated as a surgical emergency. Patients with intestinal malrotation present symptoms such as the following: gastric or bilious vomiting, GERD, nausea, anorexia, abdominal distension or intermittent chronic abdominal pain, constipation, diarrhea, bloody stools, and stunted growth. However, some patients may not demonstrate any of the above symptoms or be asymptomatic. Approximately 75% of patients with intestinal malrotation present features of GERD or vomiting bile, but in the remaining 25% of patients, GERD is characteristic of GI symptoms and may go unnoticed. In these patients, UGI series followed by intestinal transit remains the study of choice to rule out anatomic malformations or disorders of the digestive tract such as intestinal malrotation or volvulus.

Medicamentos más utilizados en pacientes ancianos mexicanos / Pattern of drugs prescribed in Mexican older patients

Como grupo poblacional, los ancianos sufren una mayor cantidad de enfermedades que las personas jóvenes, por lo que consumen significativamente más medicamentos. Un estudio hecho en los Estados Unidos de América, indica que aproximadamente el 77% de las personas de 65 años y más toman al menos un medicamento y aunque representan solo el 12% de la población, consumen aproximadamente el 30% de todos los que se venden. En promedio el número de medicamentos que dicha población recibe al mismo tiempo varían entre 1,5 y 4,2. Además de ser costoso, el uso múltiple representa un riesgo clínico importante que combinado con los cambios fisiológicos relacionados con la edad, aumentan la probabilidad de efectos adversos. En el presente estudio se describe el patrón de consumo de medicamentos basado en trabajos previos realizados en ancianos mexicanos, así como su comparación con estudios llevados a cabo en poblaciones de otros países. Se encontró que los medicamentos que más se prescriben son los dirigidos al sistema cardiovascular, al sistema nervioso central y los analgésicos anti-inflamatorios. Sin embargo se coincide en que es necesario establecer políticas de salud dirigidas a favorecer un mejor uso de medicamentos en los ancianos, basados en una correcta indicación del medicamento, evaluar el cumplimiento y la adherencia al tratamiento y en lo posible evitar la polifarmacia, que aseguren que el uso de fármacos contribuyan a que el paciente mejore y a evitar los riesgos por un mal uso de los medicamentos.

The elder population suffers major number of disease than younger patients; therefore, they consume a higher number of drugs than rest of populations. A recent study made in USA shows that proximately 77% of people older than 65 years old consume at least one medicament although this people represent 12% of total population but this corresponds to 30% of medications used in that country. Other reports indicate that this population consume between 1,5 and 4,2 drugs, which can result expensive and exist the clinic risk when drugs are used as polypharmacy because of the increase risk related with factors as the age and the possibility of apparition of adverse effects, which can be severe for health. In the present study we describe the pattern of medication consumption based in previous reports made in elderly Mexicans and compared with investigations from other countries. We find that the most consumed medications are those used in cardiovascular, central nervous system and analgesic-antiinflammatory. However it is concluded that health politics are required to improve the use of medicaments in elderly based in a correct prescription, evaluation in the compliance and strategies trying to avoid the use with multidrug simultaneously. Applying those politics the use of drugs will help the patient to improve their health, and eliminate the risk due to bad use of drugs.

Morbilidad y mortalidad por cáncer: experiencia del Centro Estatal de Cancerología de la SSA del Estado de Durango, México / Morbidity and mortality from cancer: experience of the State Center of Cancer from the SSA of Durango State, Mexico

OBJETIVO: En este estudio evaluamos el primer reporte de las estadísticas del cáncer en el Centro Estatal de Cancerología (CEC-Durango), México. MÉTODOS: Se realizó un estudio longitudinal retrospectivo, del período comprendido de enero de 2001 a diciembre de 2003, para conocer la morbimortalidad por cáncer de acuerdo con el sexo y edad, identificando sus características y tendencias. RESULTADOS: Desde la niñez hasta los 64 años de edad se observó un incremento en el número de casos, para disminuir en las últimas etapas de la vida. Durante la etapa pediátrica existe una alta tasa de casos de leucemia para niños y niñas, seguidas de tumores del sistema nervioso central (SNC) en niños y de osteosarcomas en las niñas. En los adultos, la mayoría de casos se observaron entre los 55 y 64 años de edad, para disminuir en la senescencia. Existen más casos en mujeres que en hombres; el cáncer cervicouterino (CaCu) y el cáncer de mama ocupan el primer lugar en las mujeres, y los tumores del SNC y el cáncer de pulmón en los hombres. El número total de casos disminuye conforme aumenta la edad de los sujetos. CONCLUSIONES: Hay diferencias en la morbilidad y la mortalidad por cáncer de acuerdo con la etapa de crecimiento y desarrollo de los individuos. La tasa de mortalidad general fue de 10 por ciento del total de casos. La mortalidad se vio incrementada exponencialmente a medida que se incrementa la edad de los sujetos. La mayoría de las muertes correspondió a grupos entre 15 a 24 años de edad y de 45 a 64 años en los hombres, y en las mujeres de 35 a 44 años, y después de los 65 años en ambos grupos.

PURPOSE: In this study, we evaluate the first report of cancer statistics of the Oncology State Center-Durango Mexico. METHODS: This is a retrospective longitudinal analysis of morbidity and mortality from cancer according to chronological age. RESULTS: From childhood to 64 years it was observed an increase in the number of cases to decrease in latter stages. On pediatrics age, there is a high rate of cases of leukemia for boys and girls, followed by Central Nervous System (CNS) tumors in boys and osteosarcomas in girls. For adults, most of cases were observed between 55 and 64 years to decrease in senescent. There are more cases in women than in men; cervical intraepithelial neoplasia (CIN) and breast cancer, for the former and CNS tumors and lung cancer for the last. The whole number of cases decreases as age increases. CONCLUSIONS: There are differences in morbidity and mortality from cancer according to stage of growth and development of the individuals. The general mortality rate was 10 percent of total cases. The mortality was increased exponentially as age increases. The majority of deaths corresponded to groups between 15 to 24 years and 45 to 64 years in men, 35 to 44 years and after 65 years in women.

Farmacoepidemiología de psicofármacos empleados en la práctica pediátrica en el Servicio de Psiquiatría Infantil del Hospital General de Durango, México / Pharmacoepidemiology of psychotropic drugs used in the Service of Child Psychiatry of the General Hospital of Durango, México

Introducción. Los psicofármacos representan una alternativa para el manejo terapéutico de trastornos mentales en niños y adolescentes pero no están exentos de eventos adversos. El objetivo de este trabajo fue determinar la prevalencia de trastornos psiquiátricos y su manejo farmacológico en niños y adolescentes del servicio de Psiquiatría Infantil del Hospital General de Durango-SSA. Métodos. Se revisaron retrospectivamente las historias clínicas y se realizó la historia farmacológica, a partir de los expedientes clínicos, de 111 pacientes en edades comprendidas entre 2 y 17 años, bajo tratamiento durante un año calendario. Resultados. El trastorno más frecuente (23.4%) correspondió a déficit de atención e hiperactividad (TDAH); el mismo porcentaje de los pacientes recibía monoterapia, mientras que el resto requirieron de polifarmacia (75.6%). Los fármacos habitualmente prescritos son antipsicóticos y antidepresivos; además, regularmente se usan combinaciones de estos. Conclusiones. Este trabajo está encaminado a establecer las prioridades clínicas, para realizar estudios futuros de farmacogenética y farmacocinética de los psicofármacos de más uso en pediatría, a través del conocimiento farmacoepidemiológico, con la finalidad de ayudar a mejorar la eficacia y seguridad de los psicofármacos y orientar hacia una terapéutica individualizada.

Background. Psychoactive drugs represent an alternative for the management of mental disorders during infancy and adolescence, which are not exempt from adverse events. We undertook this study to determine the prevalence of psychiatric disorders and their pharmacological management in children and adolescents who attend the Child Psychiatry Service of the General Hospital of Durango, México. Methods. Clinical and pharmacological histories of 111 patients from 2 to 17 years of age under treatment for 1 year in the Service of Infantile Psychiatry of the General Hospital of Durango (SSA) were reviewed. Results. The most frequent disorder found was attention deficit hyperactivity disorder (ADHD) (23.4%). Monotherapy was used in 23.4% of the patients, whereas in 75.6% of the cases polypharmacy was used. The most common prescribed drugs were antipsychotics, antidepressants and their combinations. Conclusion. This study emphasizes pharmacoepidemiological knowledge with the purpose of improving efficiency and safety of drug use in an attempt to optimize and individualize treatment with psychoactive drugs in pediatric patients.

Pharmacokinetics of digoxin in children with congestive heart failure aggravated by other diseases / Farmacocinética de la digoxina en niños con insuficiencia cardiaca congestiva agravada por otras enfermedades

Objective. To determine individual digoxin level variations and the effect of some common diseases those aggravate congestive heart failure (CHF) on digoxin pharmacokinetics in children. Design. Digoxin pharmacokinetics was evaluated in 11 children with CHF and an additional disease, such as rheumatic fever, anemia or infections. Digoxin plasma levels were monitored in patients on multiple-dose regime. Setting. Third level pediatric hospital. Results. Pharmacokinetic parameters showed extensive variation; median values were: elimination half-life 42.0 hrs (8.3-77.0), volume of distribution 1.01 L/kg (0.654-6.25), and clearance 15.0 mL/kg/h (6.0-331.8), which differed from results in patients with only CHF, reported previously. Dosage schemes in use at the Cardiology Service produced the following results: 40.5% of patients reached therapeutic levels, 10.8% toxic levels and 48.6% sub-therapeutic levels. Conclusion. The range of dosage required in order to adjust individual treatments was very wide, leading us to the conclusion that therapeutic schemes for this population should be individualized based on their pharmacokinetic parameters, and therapeutic monitoring of drugs should be performed.

El objetivo del presente estudio es determinar el efecto de algunas enfermedades que agravan la insuficiencia cardiaca congestiva (ICC) sobre la farmacocinètica de digoxina en niños. Diseño. Se estudió la farmacocinètica de digoxina en 11 niños con ICC, agravada por otras enfermedades como fiebre reumática, anemia o infecciones. Posteriormente se llevó a cabo monitoreo de los niveles de digoxina mientras seguían un règimen de dosis múltiple. Lugar. Centro de atención de tercer nivel. Resultados. Los parámetros farmacocinèticos mostraron amplia variabilidad: los valores de las medianas fueron: vida media de eliminación 42.0 horas (8.3-77.0), volumen de distribución 1.01 L/kg (0.654-6.25), y depuración 15.0 mL/kg/h (6.0-331.8) los cuales son diferentes a los de los pacientes que únicamente padecen ICC previamente reportados. Con el esquema de dosis usado en el Servicio de Cardiología se encontraron los siguientes resultados: 40.5% de las muestras de pacientes alcanzaron niveles terapèuticos, 10.8% niveles tóxicos y 48.6% subterapèuticos. Conclusión. Debido a la variación en los parámetros farmacocinèticos individuales, ocasionados por las patologías que agravan la ICC, se recomienda individualizar los esquemas de dosificación a partir de criterios farmacocinèticos, sin prescindir del monitoreo terapèutico del fármaco.

La farmacogenética y su importancia en la clínica / Pharmacogenetics and its clinical Significance

En el uso clínico de medicamentos, se ha observado con frecuencia ineficacia terapéutica o toxicidad farmacológica, las cuales pueden presentarse en algunos individuos quienes reciben tratamiento farmacológico. Debido a la presencia de algunas enzimas metabolizantes de fármacos, los medicamentos pueden participar como sustratos inhibidores o inductores de dichas enzimas, la actividad de éstas varía entre los individuos. Esta variabilidad enzimática puede ser determinada por el análisis del ADN recombinante como son: el análisis de restricción del ADN genómico Fragmentos de Restricción de Longitud Polimórfica (RFLP), y la amplificación enzimática del ADN por la Reacción en Cadena de la Polimerasa (PCR). Esta tecnología se ha empleado en estudios clínicos que permiten conocer los mecanismos de las variaciones heredadas en las respuestas a los fármacos las cuales son reguladas por los genes de cada individuo de las diferentes razas, donde estas diferencias enzimáticas también pueden estar influenciadas por hábitos nutricionales o factores ambientales. Con este trabajo pretendemos presentar la importancia que tiene el conocimiento del metabolismo de los fármacos aplicado al manejo terapéutico de individuos que presentan ineficacia terapéutica o toxicidad farmacológica.

Las directrices que rigen la terapéutica farmacológica en el recién nacido / The basis that guide pharmacological theraphy in newborn

El proceso de la vida se divide en distintas etapas vitales, una de las que más cambios sufre es la etapa de recién nacido (RN). Los cambios de origen corporal y fisiológico que se presentan en los primeros días de vida, alteran la farmacocinética y farmacodinamia de los fármacos. Además, debido a lo impredecible del desarrollo de los órganos que regulan la disposición de los medicamentos en el RN, es necesario conocer la farmacocinética de ciertos medicamentos, mientras el RN alcanza su madurez orgánica, para así ajustar la dosis de los medicamentos, sobre la base de parámetros farmacocinéticos individuales. En el presente trabajo se revisan las bases clínicas y farmacocinéticas, así como los instrumentos de control útiles para el establecimiento de una terapéutica farmacológica racional y segura en el RN.

Dosis efecto de la administración de fumarato ferroso en personas ancianas con deficiencia de hierro / Dose effect of ferrous fumarate administration in elderly persons with iron deficiency

Antecedentes: la anemia es un problema hematológico prevalente en ancianos, que afecta a 14 por ciento de los hombres y a 6 por ciento de las mujeres de la población mayor de 60 años de edad en México. Objetivo: determinar el efecto de la administración prolongada de fumarato ferroso en ancianos con deficiencia de hierro. Método: se estudió una población de 178 ancianos con edades entre 65 y 100 años, en 51 de estos sujetos (28.65 por ciento) se diagnosticaron niveles séricos anormales de hierro, menores de 80m g/dL para los hombres y 60 m g/dL para las mujeres, únicamente 21 de estos ancianos (11.8 por ciento) aceptaron participar en el estudio, en los cuales se estudió la respuesta a la administración oral de 5 mg/kg de hierro elemental durante seis meses.Los pacientes fueron clasificados según la alteración de los parámetros del metabolismo del hierro en tres grupos. (grupo 1 = 10.9 por ciento anemia; grupo 2 = 28.0 por ciento y grupo 3 = 63.0 por ciento de anemia). Resultados: la eficacia del tratamiento se evaluó por los cambios ocurridos en los parámetros hematológicos, como concentración de hierro sérico, hemoglobina, ferritina e índice de saturación, a los 0, 30, 90 y 180 días. Se observó que el tratamiento con fumarato ferroso durante seis meses produjo mejoría en la población estudiada determinada por el incremento significativo en los valores de los parámetros del metabolismo del hierro.Conclusiones: los resultados de este estudio sugieren la utilidad del tratamiento prolongado con fumarato ferroso en pacientes ancianos con deficiencia de hierro, para evitar fallas terapéuticas como consecuencia del no cumplimiento, el cual es común en ellos