Biological evaluation of combinations of tyrosine kinase inhibitors with Inecalcitol as novel treatments for human chronic myeloid leukemia.

Background: The use of tyrosine kinase inhibitors (TKIs) as a treatment for chronic myeloid leukemia (CML) has improved the natural history of the disease and increased the duration of survival. Tyrosine kinase inhibitors represent the success of target therapies that work on molecular targets, although some patients still have therapy failure. Vitamin D has antiproliferative, pro-apoptotic, and anti-angiogenic effects on cells, therefore it can be considered as a potential cancer preventative and treatment agent. Inecalcitol (TX-522) is the 14-epi-analogue of Calcitriol (1,25(OH)2-vitamin D3), and inhibits cancer cell proliferation more effectively than Calcitriol. This study was conducted to evaluate the antiproliferative and synergistic effects of the anticancer drugs Imatinib and Dasatinib in combinations with Inecalcitol on human chronic myeloid leukemia K-562 cells. Method: The growth inhibitory activities of Inecalcitol, Imatinib, Dasatinib, and different combinations of one of the two drugs (Imatinib and Dasatinib) with Inecalcitol, were determined in vitro using MTT assay against K-562 cell line. Results: Inecalcitol, Imatinib, and Dasatinib showed potent antiproliferative activities against K-562 cells with GI50 values of 5.6 µM, 0.327 µM, and 0.446 nM, respectively. Combinations of Imatinib or Dasatinib with different concentrations of Inecalcitol increased significantly the antiproliferative activities and potencies of both drugs (****p < 0.0001), with optimal GI50 values of 580 pM (Imatinib) and 0.51 pM (Dasatinib). Furthermore, the combination treatments showed synergistic interaction between the antileukemic drugs and Inecalcitol, with combination indices (CI) < 1. Conclusion: The study demonstrated that the human chronic myeloid leukemia K-562 cells were subjected to a synergistic growth inhibitory impact when antileukemic drugs (Imatinib or Dasatinib) were combined with Inecalcitol, therefore, it is recommended that these combinations be viewed as promising novel antileukemic medications and used in place of individual medications with lower dosages and negligible side effects in the treatment of CML.

Secondary structure prediction of long noncoding RNA: review and experimental comparison of existing approaches.

MOTIVATION: In contrast to messenger RNAs, the function of the wide range of existing long noncoding RNAs (lncRNAs) largely depends on their structure, which determines interactions with partner molecules. Thus, the determination or prediction of the secondary structure of lncRNAs is critical to uncover their function. Classical approaches for predicting RNA secondary structure have been based on dynamic programming and thermodynamic calculations. In the last 4 years, a growing number of machine learning (ML)-based models, including deep learning (DL), have achieved breakthrough performance in structure prediction of biomolecules such as proteins and have outperformed classical methods in short transcripts folding. Nevertheless, the accurate prediction for lncRNA still remains far from being effectively solved. Notably, the myriad of new proposals has not been systematically and experimentally evaluated. RESULTS: In this work, we compare the performance of the classical methods as well as the most recently proposed approaches for secondary structure prediction of RNA sequences using a unified and consistent experimental setup. We use the publicly available structural profiles for 3023 yeast RNA sequences, and a novel benchmark of well-characterized lncRNA structures from different species. Moreover, we propose a novel metric to assess the predictive performance of methods, exclusively based on the chemical probing data commonly used for profiling RNA structures, avoiding any potential bias incorporated by computational predictions when using dot-bracket references. Our results provide a comprehensive comparative assessment of existing methodologies, and a novel and public benchmark resource to aid in the development and comparison of future approaches. AVAILABILITY: Full source code and benchmark datasets are available at: https://github.com/sinc-lab/lncRNA-folding. CONTACT: lbugnon@sinc.unl.edu.ar.

Deep Learning for the discovery of new pre-miRNAs: Helping the fight against COVID-19.

The Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) has been recently found responsible for the pandemic outbreak of a novel coronavirus disease (COVID-19). In this work, a novel approach based on deep learning is proposed for identifying precursors of small active RNA molecules named microRNA (miRNA) in the genome of the novel coronavirus. Viral miRNA-like molecules have shown to modulate the host transcriptome during the infection progression, thus their identification is crucial for helping the diagnosis or medical treatment of the disease. The existence of the mature miRNAs derived from computationally predicted miRNA precursors (pre-miRNAs) in the novel coronavirus was validated with small RNA-seq data from SARS-CoV-2-infected human cells. The results demonstrate that computational models can provide accurate and useful predictions of pre-miRNAs in the SARS-CoV-2 genome, underscoring the relevance of machine learning in the response to a global sanitary emergency. Moreover, the interpretability of our model shed light on the molecular mechanisms underlying the viral infection, thus contributing to the fight against the COVID-19 pandemic and the fast development of new treatments. Our study shows how recent advances in machine learning can be used, effectively, in response to public health emergencies. The approach developed in this work could be of great help in future similar emergencies to accelerate the understanding of the singularities of any viral agent and for the development of novel therapies. Data and source code available at: https://sourceforge.net/projects/sourcesinc/files/aicovid/.

High precision in microRNA prediction: A novel genome-wide approach with convolutional deep residual networks.

MicroRNAs (miRNAs) are small non-coding RNAs that have a key role in the regulation of gene expression. The importance of miRNAs is widely acknowledged by the community nowadays and computational methods are needed for the precise prediction of novel candidates to miRNA. This task can be done by searching homologous with sequence alignment tools, but results are restricted to sequences that are very similar to the known miRNA precursors (pre-miRNAs). Besides, a very important property of pre-miRNAs, their secondary structure, is not taken into account by these methods. To fill this gap, many machine learning approaches were proposed in the last years. However, the methods are generally tested in very controlled conditions. If these methods were used under real conditions, the false positives increase and the precisions fall quite below those published. This work provides a novel approach for dealing with the computational prediction of pre-miRNAs: a convolutional deep residual neural network (mirDNN). This model was tested with several genomes of animals and plants, the full-genomes, achieving a precision up to 5 times larger than other approaches at the same recall rates. Furthermore, a novel validation methodology was used to ensure that the performance reported in this study can be effectively achieved when using mirDNN in novel species. To provide fast an easy access to mirDNN, a web demo is available at http://sinc.unl.edu.ar/web-demo/mirdnn/. The demo can process FASTA files with multiple sequences to calculate the prediction scores and generates the nucleotide importance plots. FULL SOURCE CODE: http://sourceforge.net/projects/sourcesinc/files/mirdnn and https://github.com/cyones/mirDNN. CONTACT: gstegmayer@sinc.unl.edu.ar.

Borderline ovarian tumors: Guidelines from the French national college of obstetricians and gynecologists (CNGOF).

It is recommended to classify Borderline Ovarian Tumors (BOTs) according to the WHO classification. Transvaginal and suprapubic ultrasonography are recommended for the analysis of an ovarian mass (Grade A). In case of an undetermined ovarian lesion on ultrasonography, it is recommended to perform a pelvic MRI (Grade A) with a score for malignancy (ADNEX MR/O-RADS) (Grade C) included in the report and to formulate a histological hypothesis (Grade C). Pelvic MRI is recommended to characterize a tumor suspected of being BOT (Grade C). It is recommended to evaluate serum levels of HE4 and CA125 and to use the ROMA score for the diagnosis of indeterminate ovarian mass on imaging (grade A). If there is a suspicion of a mucinous BOT on imaging, serum levels of CA 19-9 may be proposed (Grade C). For Early Stages (ES) of BOT, if surgery without risk of tumor rupture is possible, laparoscopy with protected extraction is recommended over laparotomy (Grade C). For treatment of a bilateral serous ES BOT with a strategy to preserve fertility and/or endocrine function, bilateral cystectomy is recommended where possible (Grade B). For mucinous BOTs with a treatment strategy of fertility and/or endocrine function preservation, unilateral salpingo-oophorectomy is recommended (grade C). For mucinous BOTs treated by initial cystectomy, unilateral salpingo-oophorectomy is recommended (grade C). For serous or mucinous ES BOTs, routine hysterectomy is not recommended (Grade C). For ES BOTs, lymphadenectomy is not recommended (Grade C). For ES BOTs, appendectomy is recommended only in case of a macroscopically pathological appendix (Grade C). Restaging surgery is recommended in cases of serous BOTs with micropapillary architecture and an incomplete abdominal cavity inspection during initial surgery (Grade C). Restaging surgery is recommended for mucinous BOTs after initial cystectomy or in cases where the appendix was not examined (Grade C). If restaging surgery is decided for ES BOTs, the following procedures should be performed: peritoneal washing (grade C), omentectomy (grade B), complete exploration of the abdominal cavity with peritoneal biopsies (grade C), visualization of the appendix and appendectomy in case of a pathological macroscopic appearance (grade C) as well as unilateral salpingo-oophorectomy in case of a mucinous BOT initially treated by cystectomy (grade C). In advanced stages (AS) of BOT, it is not recommended to perform a lymphadenectomy as a routine procedure (Grade C). For AS BOT in a patient with a desire to fall pregnant, conservative treatment involving preservation of the uterus and all or part of the ovary may be proposed (Grade C). Restaging surgery aimed at removing all lesions, not performed initially, is recommended for AS BOTs (Grade C). After treatment, follow-up for a duration greater than 5 years is recommended due to the median recurrence time of BOTs (Grade B). It is recommended that a systematic clinical examination be carried out during follow-up of a treated BOT (Grade B). If the determination of tumor markers is normal preoperatively, the routine dosage of tumor markers in BOT follow-up is not recommended (Grade C). In case of an initial elevation in serum CA 125 levels, it is recommended to monitor CA 125 during follow up (Grade B). In case of conservative treatment, it is recommended to use transvaginal and transabdominal ultrasound during follow up of a treated BOT (Grade B). In the event of a BOT recurrence in a woman of childbearing age, a second conservative treatment may be proposed (Grade C). A consultation with a physician specialized in Assisted Reproductive Technique (ART) should be offered in the case of BOTs in women of childbearing age (Grade C). When possible, a conservative surgical strategy is recommended to preserve fertility in women of childbearing age (Grade C). In the case of optimally treated BOT, there is no evidence to contraindicate the use of ART. The use of hormonal contraception after serous or mucinous BOT is not contraindicated (Grade C). After management of mucinous BOT, for women under 45 years, given the benefit of Hormonal Replacement Therapy (HRT) on cardiovascular and bone risks, and the lack of hormone sensitivity of mucinous BOTs, it is recommended to offer HRT (Grade C). Over 45 years of age, HRT can be prescribed in case of a climacteric syndrome after individual benefit to risk assessment (Grade C).

DL4papers: a deep learning approach for the automatic interpretation of scientific articles.

MOTIVATION: In precision medicine, next-generation sequencing and novel preclinical reports have led to an increasingly large amount of results, published in the scientific literature. However, identifying novel treatments or predicting a drug response in, for example, cancer patients, from the huge amount of papers available remains a laborious and challenging work. This task can be considered a text mining problem that requires reading a lot of academic documents for identifying a small set of papers describing specific relations between key terms. Due to the infeasibility of the manual curation of these relations, computational methods that can automatically identify them from the available literature are urgently needed. RESULTS: We present DL4papers, a new method based on deep learning that is capable of analyzing and interpreting papers in order to automatically extract relevant relations between specific keywords. DL4papers receives as input a query with the desired keywords, and it returns a ranked list of papers that contain meaningful associations between the keywords. The comparison against related methods showed that our proposal outperformed them in a cancer corpus. The reliability of the DL4papers output list was also measured, revealing that 100% of the first two documents retrieved for a particular search have relevant relations, in average. This shows that our model can guarantee that in the top-2 papers of the ranked list, the relation can be effectively found. Furthermore, the model is capable of highlighting, within each document, the specific fragments that have the associations of the input keywords. This can be very useful in order to pay attention only to the highlighted text, instead of reading the full paper. We believe that our proposal could be used as an accurate tool for rapidly identifying relationships between genes and their mutations, drug responses and treatments in the context of a certain disease. This new approach can certainly be a very useful and valuable resource for the advancement of the precision medicine field. AVAILABILITY AND IMPLEMENTATION: A web-demo is available at: http://sinc.unl.edu.ar/web-demo/dl4papers/. Full source code and data are available at: https://sourceforge.net/projects/sourcesinc/files/dl4papers/. CONTACT: lbugnon@sinc.unl.edu.ar. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

[Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Short Text]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Texte court.

This work was carried out under the aegis of the CNGOF (Collège national des gynécologues et obstétriciens français) and proposes guidelines based on the evidence available in the literature. The objective was to define the diagnostic and surgical management strategy, the fertility preservation and surveillance strategy in Borderline Ovarian Tumor (BOT). No screening modality can be proposed in the general population. An expert pathological review is recommended in case of doubt concerning the borderline nature, the histological subtype, the invasive nature of the implant, for all micropapillary/cribriform serous BOT or in the presence of peritoneal implants, and for all mucinous or clear cell tumors (grade C). Macroscopic MRI analysis should be performed to differentiate the different subtypes of BOT: serous, seromucinous and mucinous (intestinal type) (grade C). If preoperative biomarkers are normal, follow up of biomarkers is not recommended (grade C). In cases of bilateral early serous BOT with a desire to preserve fertility and/or endocrine function, it is recommended to perform a bilateral cystectomy if possible (grade B). In case of early mucinous BOT, with a desire to preserve fertility and/or endocrine function, it is recommended to perform a unilateral adnexectomy (grade C). Secondary surgical staging is recommended in case of serous BOT with micropapillary appearance and uncomplete inspection of the abdominal cavity during initial surgery (grade C). For early-stage serous or mucinous BOT, it is not recommended to perform a systematic hysterectomy (grade C). Follow up after BOT must be pursued for more than 5 years (grade B). Conservative treatment involving at least the conservation of the uterus and a fragment of the ovary in a patient wishing to conceive may be proposed in advanced stages of BOT (grade C). A new surgical treatment that preserves fertility after a first non-invasive recurrence may be proposed in women of childbearing age (grade C). It is recommended to offer a specialized consultation for Reproductive Medicine when diagnosing BOT in a woman of childbearing age. Hormonal contraceptive use after serous or mucinous BOT is not contraindicated (grade C).

[Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Fertility]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Fertilité.

OBJECTIVES: Borderline ovarian tumours (BOT) represent around 15% of all ovarian neoplasms and are more likely to be diagnosed in women of reproductive age. Overall, given the epidemiological profile of BOT and their favourable prognosis, ovarian function and fertility preservation should be systematically considered in patients presenting these lesions. METHODS: The research strategy was based on the following terms: borderline ovarian tumour, fertility, fertility preservation, infertility, fertility-sparing surgery, in vitro fertilization, ovarian stimulation, oocyte cryopreservation, using PubMed, in English and French. RESULTS AND CONCLUSIONS: Fertility counselling should become an integral part of the clinical management of women with BOT. Patients with BOT should be informed that surgical management of BOT may cause damage ovarian reserve and/or peritoneal adhesions. Nomogram to predict recurrence, ovarian reserve markers and fertility explorations should be used to provide a clear and relevant information about the risk of infertility in patients with BOT. Fertility-sparing surgery should be considered for young women who wish preserving their fertility when possible. There is insufficient evidence to claim a causal relation between controlled ovarian stimulation (COS) and BOT. However, in case of poor prognosis factors, the use of COS should be considered cautiously through a multidisciplinary approach. In case of infertility after surgery for BOT, COS can be performed without delay, once histopathological diagnosis of BOT is confirmed. There is insufficient consistent evidence that fertility drugs and COS increase the risk of recurrence of BOT after conservative management. The conservative surgical treatment can be associated to oocyte cryopreservation considering the high risk of recurrence of the disease. In women with BOT recurrence in a single ovary and in women with bilateral ovarian involvement when the conservative management is not possible, other fertility preservation strategies are available, but still experimental.

Genome-wide hairpins datasets of animals and plants for novel miRNA prediction.

This article makes available several genome-wide datasets, which can be used for training microRNA (miRNA) classifiers. The hairpin sequences available are from the genomes of: Homo sapiens, Arabidopsis thaliana, Anopheles gambiae, Caenorhabditis elegans and Drosophila melanogaster. Each dataset provides the genome data divided into sequences and a set of computed features for predictions. Each sequence has one label: i) "positive": meaning that it is a well-known pre-miRNA, according to miRBase v21; or ii) "unlabeled": indicating that the sequence has not (yet) a known function and could be a possible candidate to novel pre-miRNA. Due to the fact that selecting an informative feature set is very important for a good pre-miRNA classifier, a representative feature set with large discriminative power has been calculated and it is provided, as well, for each genome. This feature set contains typical information about sequence, topology and structure. Dataset was publically shared in https://sourceforge.net/projects/sourcesinc/files/mirdata/.

Medical techniques of fertility preservation in the male and female.

Therapeutic advances in many medical fields have led to the need to consider patient quality of life after curative medico-surgical treatments for malignancy. Thus, it has become a major issue for young patients to preserve the ability to become "genetic" parents, with their own gametes. While the preservation of male fertility has been an established technique for more than 30 years, it is only in the last decade that progress in cryopreservation techniques has allowed surgeons to offer successful oocyte and ovarian tissue cryobanking. However, in addition to the still experimental nature of some fertility preservation techniques, this practice also raises many ethical and moral questions.

The proteome pattern cGvHD_MS14 allows early and accurate prediction of chronic GvHD after allogeneic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be curative, but is associated with significant morbidity and mortality. Chronic graft-versus-host disease (cGvHD), characterized by inflammation and fibrosis of multiple target organs, considerably contributes to the morbidity and mortality even years after allo-HSCT. Diagnosis of cGvHD is based on clinical features and histology of biopsies. Here, we report the generation of a urinary cGvHD-specific proteome-pattern (cGvHD_MS14) established by capillary electrophoresis-mass spectrometry to predict onset and severity of cGvHD as an unbiased laboratory test. cGvHD_MS14 was evaluated on samples from 412 patients collected prospectively in four transplant centers. Sensitivity and specificity was 84 and 76% by cGvHD_MS14 classification. Sensitivity further increased to 93% by combination of cGvHD_MS14 with relevant clinical variables to a logistic regression model. cGvHD was predicted up to 55 days prior to clinical diagnosis. Acute GvHD is not recognized by cGvHD_MS14. cGvHD_MS14 consists of 14 differentially excreted peptides, six of those have been sequenced to date and are fragments from thymosin ß-4, eukaryotic translation initiation factor 4γ2, fibrinogen ß-chain or collagens. In conclusion, the cGvHD_MS14-pattern allows early, highly sensitive and specific prediction of cGvHD as an independent diagnostic criterion of clinical diagnosis potentially allowing early therapeutic intervention.

Incidence of hip fracture in Barranquilla, Colombia, and the development of a Colombian FRAX model.

A FRAX model for Colombia was released June 30, 2010. This article describes the data used to develop the Colombian FRAX model and illustrates its features compared to other countries. Hip fracture cases aged 50 years or more who were referred to all hospitals serving the city of Barranquilla were identified prospectively over a 3-year period (2004-2006). Age- and sex-stratified hip fracture incidence rates were computed using the 2005 census. Present and future numbers of hip fracture cases in Colombia were calculated from the age- and sex-specific incidence and the national population demography. Mortality rates for 1999 were extracted from nationwide databases and used to estimate hip fracture probabilities. For other major fractures (clinical vertebral, forearm, and humerus), incidence rates were imputed, using Swedish ratios for hip to other major osteoporotic fracture, and used to construct the FRAX model. Incidence of hip fracture increased with age, more markedly in women than in men. Over all ages, the female to male ratio was 1.7. By extrapolation, there were estimated to be 7,902 new hip fracture cases (2,673 men, 5,229 women) in Colombia in 2010, which was predicted to increase to 22,720 cases (7,568 men, 15,152 women) in 2035. The 10-year probability of hip or major fracture was increased in patients with a clinical risk factor, lower BMI, female gender, a higher age, and a decreased BMD T score. The remaining lifetime probability of hip fracture at the age of 50 years was 2.5 and 4.7 % in men and women, respectively, which were lower than rates in a Mexican population (3.8 and 8.5 %, respectively) and comparable with estimates for Venezuela (2.4 and 7.5 %, respectively). The FRAX tool is the first country-specific fracture-prediction model available in Colombia. It is based on the original FRAX methodology, which has been externally validated in several independent cohorts. Despite some limitations, the strengths make the Colombian FRAX tool a good candidate for implementation into clinical practice.

Liver transplantation for children--the Red Cross Children's Hospital experience.

UNLABELLED: Liver transplantation for infants and children has been available in South Africa at a single centre, the only established service in Sub-Saharan Africa, for more than a decade. Current concerns have shifted from an initial target of early post-transplant survival to quality of life in the long-term. MATERIALS AND METHODS: Since 1985, 225 infants and children have been assessed, with 146 accepted for transplantation. Sixty-nine have had 71 orthotopic liver transplants (OLTx). Biliary atresia was the most frequent diagnosis (54%) followed by acute liver failure (ALF) (15%). Waiting list mortality has remained high (23%), particularly for the ALF group (50%). Forty-three were reduced size transplants with donor: recipient weight ratios ranging from 2:1 to 11:1. Twenty-seven were <10 kg. RESULTS: Fifty (74%) survive 1 month-12 years post-transplant. Actuarial survival after 1996 since HBV core antibody positive donor livers were refused and prophylactic IV ganciclovir used has been >82%. Early post-OLTx mortality was low (5%), one primary non-function, one IVC thrombosis, one PV thrombosis, but late morbidity and mortality (20%) was mainly due to viral infection: de novo hepatitis B (five patients, three deaths), EBV-related post-transplantation lymphoproliferative disease (PTLPD) (eight patients, six deaths) and CMV disease (11 patients, five deaths). Tuberculosis prophylaxis, required in six cases, resulted in major morbidity in two and mortality in one. Poor compliance played a significant role in seven deaths. Hypertension requiring medication along with some compromise of renal function has been present in all but two patients. However, all those of school-going age (25) attend school normally and remain in good health and only three of the survivors have abnormal liver function tests. CONCLUSIONS: Successful liver transplantation is possible in a developing country with limited resources. Scarcity of virus-free donors (HBV and HIV) leading to waiting list mortality and infrequent re-transplantation along with long-term consequences of immunosuppression (infection, lymphoma and renal toxicity) remain problems. Intense education of the caregiver and close follow-up, particularly of those living at long distances has partly addressed the compliance problem.

Efectividad de la administracion de sales de rehidratación oral (SRO), en el marco del programa EDA / Effectiveness of salts of oral rehydratation in patients that with the diagnosis of acute diarrheal disease

Objetivo: Determinar la eficacia que tienen las sales de rehidratación oral en los pacientes con el diagnóstico de Enfermedad Diarréica Aguda (EDA). Diseño: Revisión sistemática de estudios controlados aleatorizados. Fuentes de datos: Medline (1966-2001), Cochrane Library, (1993 a 2001) y Ovid (1982 a 2001), bibliografías de los estudios incluidos; que fueron revisadas si estas eran pertinentes. Estudio: 31 estudios que incluían 4518 pacientes aleatorizados. Métodos: Los estudios seleccionados fueron reagrupados en subgrupos por los componentes que se comparaban en la intervención. Los cuales además de las sales de rehidratación oral (SRO) incluían soluciones con baja osmolaridad, con base en arroz, o con la adición de suplementos como citrato, zinc, alanina, lactoalbulina, y glutamina. Resultados: Una alta proporción de estudios mostró la ventaja que tienen las sales de rehidratación oral recomendadas por la Organización Mundial de la Salud y la Organización Panamericana de la Salud al mejorar el cuadro clínico de los pacientes con diagnósticos de diarrea y deshidratación. Se evidenció una mejor respuesta con las SRO de osmolaridad baja, aunque no en todos los estudios fue estadísticamente significativo. Conclusiones. Este trabajo demostró que las sales de rehidratación oral reducen el número de deposiciones, disminuyen el tiempo de evolución de la diarrea, disminuyeron la tasa de mortalidad y el tiempo de estancia en hospitales

Anal achalasia after pull-through operations for Hirschsprung's disease -- preliminary experience with topical nitric oxide.

INTRODUCTION: Following definitive pull-through for Hirschsprung's disease (HD), a minority of patients develop constipation, incontinence and enterocolitis. The cause for these symptoms in some of the patients is believed to be "internal sphincter achalasia" related to abnormal innervation of the sphincter, with an absent anorectal relaxation reflex. Transanal myectomy, posterior sagittal rectal myectomy, anal dilatation and even intrasphincter injection of botulinum toxin have been used to solve this problem. Nitric oxide (NO) has been identified as the chemical messenger of the intrinsic non-adrenergic, non-cholinergic pathway mediating relaxation of the normal internal anal sphincter when applied topically. BACKGROUND/PURPOSE: To evaluate the effect of topical isosorbide dinitrate (DTN) applied to the anus and its role in the management of patients with HD after pull-through who have ongoing difficulties in stool evacuation. MATERIAL AND METHODS: Four children, aged 2, 5, 7 and 13 years, who all underwent the Soave operation for Hirschsprung's disease, were assessed. Three patients had recurrent episodes of enterocolitis, and all had symptoms of difficulty in rectal/colonic evacuation. Conservative treatment of repeated anal dilatation under anaesthesia had failed to improve symptoms. A rectal myectomy and conversion of Soave to Duhamel procedure had been done in 2 without significant improvement in symptoms. In all patients, ano-rectal manometry was performed before and after application of DTN paste (1 mg/kg/day in two separate doses) which was continued for a minimum period of 3 weeks. Results. Marked symptom improvement was noted in all 4 children. On manometric assessment the median maximum pressure (pre-DTN application) was 165 mm Hg (range 96 - 250), the median sphincter length 2.7 cm (range 2.3 - 3.1) and the high-pressure zone (HPZ) median length 1.6 cm (range 1.2 - 2.1). After application of DTN paste, the maximum pressure dropped by a median of 88 mm Hg (range 46 - 90), total sphincter length shortened to a median of 2.1 cm and the HPZ by a median total length of 1.4 cm (range 0.01 - 0.9). In addition, vector volume was reduced by a median of 59 % (range 40.5 - 77). CONCLUSION: From these results, it is evident that DTN paste is not only an adjunct in the investigation, but can also be used as a temporary form of treatment of obstructive symptoms in Hirschsprung's disease patients.

Aspectos sobre diseño y tamaño de muestra en estudios de pruebas diagnósticas / Aspects related with the meaning and development of diagnosis test

En este artículo se presentan algunas consideraciones generales y particulares con respecto al significado y desarrollo de los estudios sobre pruebas diagnósticas. El centro del mismo se dedica a la formulación de los elementos necesarios que subyacen al cálculo del tamaño de muestra en este tipo particular de diseños

Eficacia de la inmunización contra el antígeno de superficie de la hepatitis B en estudiantes de la facultad de odontología de la Universidad Autónoma de Manizales, Colombia, 1997 / Efficacy of immunization against surface antigens of hepatitis B in students from the University of Manizales School of Dentistry

Las estrategias mundiales orientadas a la prevención de la hepatitis B incluyen la inmunization activa contra el virus, especialmente del personal vinculado a la atención en salud, debido a su exposición permanente a sangre y fluidos corporales de pacientes potencialmente infecciosos. Teniendo en cuenta que la inmunización activa puede no ser exitosa en el 100 por ciento de los casos, en el presente estudio se determinó la eficacia de la vacuna recombinante Engerix Smith Kline en una muestra de 56 estudiantes de la Facultad de Odontología de la Universidad Autónoma de Manizales. Para tal efecto, se determinó la presencia de anticuerpos al virus de la hepatitis B en el suero de las personas inmunizadas, utilizando la técnica de análisis inmunoenzimático (Abbott). Los resultados muestran que en 91.07 por ciento de los casos se logró la seroprotección (IC 95 por ciento: 87,27 a 94,87 por ciento). En 8,93 por ciento, la inmunización no fue eficaz. Teniendo en cuenta los datos anteriores se considera relevante que los programas de inmmunización contra el virus de la hepatitis B incluyan la monitorización de la respuesta inmunológica, con el fin de identificar aquellas personas no respondedoras que ameritan medidas adicionales de protección

[Vertebral hemangioma symptomatic during pregnancy. A case report and review of the literature]. / Hémangiome vertébral symptomatique au cours de la grossesse. A propos d'un cas et revue de la littérature.

Vertebral hemangioma is a relatively frequent but rarely symptomatic tumor. Physiologic changes during pregnancy may lead to spinal cord compression due to tumor expansion. We report a case of vertebral hemangioma during pregnancy: a 28-year-old woman, third trimester, third gestation, consulted for paraplegia of rapid onset; Magnetic resonance imaging showed a lesion of the 9th thoracic vertebra; a cesarean section was done, followed by laminectomy with partial symptom relief; pathology showed a benign vertebral hemangioma and treatment was completed with radiotherapy.

Postmortem cesarean section following maternal blast injury: case report.

We report a postmortem cesarean section resulting in fetal survival, performed 25 minutes after maternal blast injury. The time interval between cardiopulmonary arrest and delivery, prior maternal health status, and continued cardiopulmonary resuscitation represent important determinants of fetal survival. Improvement in maternal hemodynamic condition may potentially occur following the procedure. Postmortem cesarean section is advised in the event of fatal maternal trauma since it may result in fetal salvage.