Canine as a Comparative and Translational Model for Human Mammary Tumor / 한국유방암학회지

Despite the advances in research and treatment of human breast cancer, its incidence rate continues to increase by 0.5% per year, and the discovery of novel therapeutic strategies for specific subtypes of human breast cancer remains challenging. Traditional laboratory mouse models have contributed tremendously to human breast cancer research. However, mice do not develop tumors spontaneously; consequently, genetically engineered mouse models or patient-derived xenograft models are often relied upon for more sophisticated human breast cancer studies. Since human breast cancer develops spontaneously, there is a need for alternative, yet complementary, models that can better recapitulate the features of human breast cancer to better understand the molecular and clinical complexities of the disease in developing new therapeutic strategies. Canine mammary tumors are one such alternative model that share features with human breast cancer, including prevalence rate, subtype classification, treatment, and mutational profiles, all of which are described in this review.

Trypanosuppressive effects of Kolaviron may be associated with down regulation of Trypanothione reductase in Trypanosoma congolense infection

@#Trypanothione reductase is a key enzyme that upholds the redox balance in hemoflagellate protozoan parasites such as T. congolense. This study aims at unraveling the potency of Kolaviron against trypanothione reductase in T. congolense infection using Chrysin as standard. The experiment was performed using three different approaches; in silico, in vitro and in vivo. Kolaviron and Chrysin were docked against trypanothione reductase, revealing binding energies (-9.3 and -9.0 kcal/mol) and Ki of 0.211μM and 0.151μM at the active site of trypanothione reductase as evident from the observed strong hydrophobic/hydrogen bond interactions. Parasitized blood was used for parasite isolation and trypanothione reductase activity assay using standard protocol. Real-time PCR (qPCR) assay was implored to monitor expression of trypanothione reductase using primers targeting the 177-bp repeat satellite DNA in T. congolense with SYBR Green to monitor product accumulation. Kolaviron showed IC50 values of 2.64μg/ml with % inhibition of 66.78 compared with Chrysin with IC50 values of 1.86μg/ml and % inhibition of 53.80. In vivo studies following the administration of these compounds orally after 7 days post inoculation resulted in % inhibition of Chrysin (57.67) and Kolaviron (46.90). Equally, Kolaviron relative to Chrysin down regulated the expression trypanothione reductase gene by 1.352 as compared to 3.530 of the infected group, in clear agreement with the earlier inhibition observed at the fine type level. Overall, the findings may have unraveled the Kolaviron potency against Trypanosoma congolense infection in rats.

Design and implementation of a clinical laboratory information system in a low-resource setting

Background: Reducing laboratory errors presents a significant opportunity for both cost reduction and healthcare quality improvement. This is particularly true in low-resource settings where laboratory errors are further exacerbated by poor infrastructure and shortages in a trained workforce. Informatics interventions can be used to address some of the sources of laboratory errors.Objectives: This article describes the development process for a clinical laboratory information system (LIS) that leverages informatics interventions to address problems in the laboratory testing process at a hospital in a low-resource setting.Methods: We designed interventions using informatics methods for previously identified problems in the laboratory testing process at a clinical laboratory in a low-resource setting. First, we reviewed a pre-existing LIS functionality assessment toolkit and consulted with laboratory personnel. This provided requirements that were developed into a LIS with interventions designed to address the problems that had been identified. We piloted the LIS at the Kamuzu Central Hospital in Lilongwe, Malawi.Results: We implemented a series of informatics interventions in the form of a LIS to address sources of laboratory errors and support the entire laboratory testing process. Custom hardware was built to support the ordering of laboratory tests and review of laboratory test results.Conclusion: Our experience highlights the potential of using informatics interventions to address systemic problems in the laboratory testing process in low-resource settings. Implementing these interventions may require innovation of new hardware to address various contextual issues. We strongly encourage thorough testing of such innovations to reduce the risk of failure when implemented

Multicentre study on dynamic contrast computed tomography findings of focal liver lesions with clinical and histological correlation

Background: Current advancements in dynamic contrast imaging of the liver have enabled increased sensitivity in the diagnosis of liver lesions. Evaluation and characterisation of the enhancement pattern of liver lesions in respect to the liver parenchyma aids in making a specific diagnosis.Objectives: The aim of this study was to determine the liver findings on dynamic contrast computed tomography (CT) scanning and correlate them with clinicopathologic findings. Methods: This prospective cross-sectional study included 61 patients and took place between August 2017 and February 2018. Dynamic contrast CT was performed and the images were evaluated by two experienced radiologists. Correlation of the CT findings with histology results from an ultrasound-guided biopsy was done. Data analysis was performed using SPSS version 20.0. Results: Hepatocellular carcinoma (HCC) was the most common malignant lesion seen and showed three patterns of enhancement: homogenous, abnormal internal vessels and heterogeneous enhancement. Abnormal internal vessel pattern was most specific (90.6%) and showed a high positive predictive value (PPV) of 78.6%. Rapid washout showed a specificity of 87.5% and a PPV of 72.2% in the diagnosis of HCC. Dynamic contrast CT scan had a sensitivity of 93%, specificity of 50%, PPV of 91% and diagnostic accuracy of 95.5% in differentiation of benign and malignant liver lesions. Considering only Liver Imaging Reporting and Data System (LI-RADS) category 5 as conclusive for HCC diagnosis, our study did not miss a significant number of HCCs. Liver Imaging Reporting and Data System category 5 showed specificity of 81.3% and PPV of 75%. Conclusion: Enhancement patterns on a dynamic contrast CT scan of the liver are useful in the interpretation of CT images for specific diagnoses

Off-Label Application of Pipeline Embolization Device for Intracranial Aneurysms / 신경중재치료의학

PURPOSE: The Pipeline embolization device (PED) is approved in the USA for treating giant and large aneurysms arising from the petrous to superior hypophyseal segments of the internal carotid artery in patients older than 21 years of age. This study investigates off-label PED results in a large cohort. MATERIALS AND METHODS: Retrospective, single-center review of all patients who had off-label PED surgery. RESULTS: Sixty-two aneurysms (48 patients) underwent off-label PED treatment from 2012–2017. There were 44 females and four males (age 21 to 75 years; mean/median, 54.3/55.0 years). The most common presenting symptom was headache (47/62, 75.8%). All aneurysms were in the anterior circulation. Aneurysm size ranged from 1.4 to 25.0 mm (mean/median, 7.6/6.9 mm). Fifty-two aneurysms had post-operative imaging with total/near-complete occlusion of 84.6% (44/52). Aneurysm-based operative near-term complication rate was 9.7% while there were no permanent complications. For aneurysms and headache, 86.7% improved/resolved after embo-surgery, and were four times more likely to have a better clinical outcome (resolved or improved symptoms) after surgery (odds ratio [OR], 4.333; P=0.0325). Left-sided aneurysms had a higher occlusion rate (OR, 20; P=0.0073). Hypertension (OR, 4.2; P=0.0332) and smoking (OR, 7; P=0.0155) were more prone towards aneurysm occlusion. Patients without a family history were 14 times more likely to have favorable imaging outcome (P=0.0405). There is no difference of occlusion rates between untreated and previously treated aneurysms (P=0.6894). Overall, occlusion rate decreased by 14% with an increase of aneurysm size by 1 mm (P=0.0283). CONCLUSION: For anterior circulation aneurysms, the off-label application of PED is as effective and safe as reported for on-label intracranial aneurysms.

Investigation of polymorphisms in Plasmodium falciparum hrp2, hrp3, aldolase and pldh genes and their impact on the performance of malaria rapid diagnostic tests in Papua New Guinea

@#The World Health Organization (WHO) recommends that parasitological confirmation of clinical malaria diagnosis be performed before antimalarial treatment is administered. Malaria rapid diagnostic tests (RDTs) represent a valuable tool for prompt and efficient diagnosis of malaria in settings where microscopic diagnosis is unavailable or unreliable. Concerns remain, however, that Plasmodium falciparum polymorphisms in the genes coding the antigens detected by RDT could impact on RDT performance. Using field isolates of Plasmodium falciparum, we aimed to characterize genetic variability in histidine-rich proteins 2 and 3 (PfHRP-2 and PfHRP-3), aldolase (ALD) and Plasmodium lactate dehydrogenase (pLDH) genes and to evaluate their impact on the performance of RDT. Pfhrp-2, Pfhrp-3, aldolase and pldh were amplified using polymerase chain reaction (PCR) and sequenced. Genetic variation was observed in pfhrp-2 and pfhrp-3 genes while aldolase and pldh showed high levels of conservation. These findings suggest that RDTs based on pLDH and ALD are reliable in the study settings where there is intense diversity or polymorphisms of histidine-rich protein (HRP). Nevertheless, there is no evidence from this study to suggest that RDTs based on the detection of PfHRP-2 and PfHRP-3 have lower sensitivity in Papua New Guinea (PNG). The results observed in this study will be used to inform the PNG National Department of Health on the continued usage of pLDH/ HRP-2 RDT for malaria diagnosis in PNG.

In vitro susceptibility of Plasmodium falciparum isolates from East New Britain Province to antimalarial drugs using a colorimetric lactate dehydrogenase assay

@#The in vitro susceptibility of Plasmodium falciparum to chloroquine (CQ), amodiaquine (AQ), monodesethylamodiaquine (mAQ) and piperaquine (PQP) antimalarial drugs was evaluated in 13 isolates from East New Britain Province of Papua New Guinea (PNG) using a colorimetric Plasmodium lactate dehydrogenase (LDH) assay. Of the 13 isolates assessed, 9 (69%) showed in vitro resistance to CQ with the concentration required to inhibit growth by 50% (IC50) ranging from 25 to 188.8 nM (geometric mean 118.7 nM). All parasites exhibited in vitro susceptibility to AQ, mAQ and PQP with their mean IC50s well below reported threshold values. Significant rank order positive correlations were observed between PQP and CQ (rs = 0.67, p <0.005) suggestive of potential in vitro cross-resistance between these two 4-aminoquinoline drugs. These results demonstrate the suitability of the enzyme-based LDH assay for assessing in vitro P. falciparum susceptibility and highlight the importance of in vitro assessment of antimalarial drugs in PNG in tandem with local therapeutic efficacy studies.

Healthcare-seeking behaviors for acute respiratory illness in two communities of Java, Indonesia: a cross-sectional survey

Understanding healthcare-seeking patterns for respiratory illness can help improve estimations of disease burden and inform public health interventions to control acute respiratory disease in Indonesia. The objectives of this study were to describe healthcare-seeking behaviors for respiratory illnesses in one rural and one urban community in Western Java, and to explore the factors that affect care seeking. From February 8, 2012 to March 1, 2012, a survey was conducted in 2520 households in the East Jakarta and Bogor districts to identify reported recent respiratory illnesses, as well as all hospitalizations from the previous 12-month period. We found that 4% [10% of those less than 5 years] of people had respiratory disease resulting in a visit to a healthcare provider in the past 2 weeks; these episodes were most commonly treated at government [33%] or private [44%] clinics. Forty-five people [0.4% of those surveyed] had respiratory hospitalizations in the past year, and just over half of these [24/45, 53%] occurred at a public hospital. Public health programs targeting respiratory disease in this region should account for care at private hospitals and clinics as well as illnesses that are treated at home in order to capture the true burden of illness in these communities

[Oops! I forgot HIV]: Resident physician self-audits and universal HIV screening

Innovations are needed to increase universal HIV screening by primary care providers. One potential intervention is self-audit feedback, which describes the process of a clinician reviewing their own patient charts and reflecting on their performance. The effectiveness of self-audit feedback was investigated using a mixed methods approach. A total of 2111 patient charts were analyzed in a quantitative pre-post intervention study design, where the intervention was providing self-audit feedback to all internal medicine residents at one institution through an annual chart review. Qualitative data generated from the subsequent resident focus group discussions explored the motivation and mechanism for change using a knowledge-attitude-behavior framework. The proportion of primary care patients screened for HIV increased from 17.9% [190/1060] to 40.3% [423/1051]. The adjusted odds ratio of a patient being screened following resident self-audited feedback was 3.17 [95% CI 2.11, 4.76, p < 0.001]. Focus group participants attributed the improved performance to the self-audit feedback. Self-audit feedback is a potentially effective intervention for increasing universal HIV screening in primary care. This strategy may be most useful in settings where [1] baseline performance is low, [2] behavioral change is provider-driven, and [3] resident trainees are targeted

A Review of Inflammatory Processes of the Breast with a Focus on Diagnosis in Core Biopsy Samples

Inflammatory and reactive lesions of the breast are relatively uncommon among benign breast lesions and can be the source of an abnormality on imaging. Such lesions can simulate a malignant process, based on both clinical and radiographic findings, and core biopsy is often performed to rule out malignancy. Furthermore, some inflammatory processes can mimic carcinoma or other malignancy microscopically, and vice versa. Diagnostic difficulty may arise due to the small and fragmented sample of a core biopsy. This review will focus on the pertinent clinical, radiographic, and histopathologic features of the more commonly encountered inflammatory lesions of the breast that can be characterized in a core biopsy sample. These include fat necrosis, mammary duct ectasia, granulomatous lobular mastitis, diabetic mastopathy, and abscess. The microscopic differential diagnoses for these lesions when seen in a core biopsy sample will be discussed.

Disability adjusted working life years (DAWLYs) of leprosy affected persons in India.

Background & objectives: Disability-adjusted life years (DALYs) have been accepted as a useful method to estimate the burden of disease, and can be adapted to determine the number of productive years lost due to the disability. DALY has been reported for many studies but not for leprosy. Hence this study was carried out in three States of India. In view of the fact that in this study, productive working years are used, the term is modified as DAWLY. Methods: A representative random sample of 150 leprosy affected persons, 50 from each States of Uttar Pradesh, West Bengal and Chhattisgarh, was chosen, and data were collected on detailed work-life history, occupation, time when leprosy was discovered, reported and treatment started, break of job/loss of income due to leprosy. The loss of wages and durations were used to compute the life-years lost due to leprosy, and summarized over the average total duration of 42 years of productive work-life from 18 to 60 years. The percentage losses were determined and differences tested for statistical significance. Results: The overall mean (± SE) disability adjusted working life years was 28.6 (±0.67), a reduction of 13.4 yr from the ideal productive working life period of 42 yr. The youngest patients with disability had a reduction of 41.4 per cent, as compared to the oldest patients. There was a significant increase in loss based on year for those whose disability started earlier (P=0.0024). Interpretation & conclusions: On an average, 30 per cent of the leprosy affected person’s work life is lost due to disability.

Bloodstream infections caused by resistant bacteria in surgical patients admitted to Modilon Hospital, Madang

In view of the dearth of information relating to antibiotic resistance in community- and hospital-acquired bacterial infections in Papua New Guinea (PNG), we carried out a prospective, hospital-based observational study of surgical patients between October 2008 and October 2009. In a sample of 115 patients (median age 30 years; 55% males) suspected of having a bloodstream infection, blood cultures were positive in 11 (10%) and a significant pathogen was isolated in 9 (8%). Staphylococcus aureus was isolated in 4 patients (44%) and 3 were methicillin resistant; all these isolates were considered community acquired because cultures were performed within 48 hours of admission. Of the remaining 5 isolates, 4 were Gram-negative organisms with at least intermediate resistance to chloramphenicol that were grown from blood taken > 48 hours post-admission and thus considered nosocomially acquired. These data suggest two distinct patterns of bacterial infection in PNG surgical inpatients that have implications for national antibiotic prescription guidelines.

The outcome of febrile neutropenic episodes in paediatric oncology at the Wendy Fitzwilliam Paediatric Hospital / La evolución clínica de los episodios neutropénicos febriles en la oncología pediátrica en el Hospital Pediátrico Wendy Fitzwilliam

OBJECTIVES: To evaluate the incidence, presentation, treatment and outcome of febrile neutropenic episodes of patients treated at the Wendy Fitzwilliam Paediatric Hospital (WFPH) in Trinidad and Tobago. METHODOLOGY: Using a retrospective cohort method, the records of all the patients registered at the Paediatric Oncology Unit at The WFPH, receiving chemotherapy for haematological or solid tumour malignancies from May 2001 to April 2008 and having episodes of febrile neutropenia were analysed. RESULTS: Seventy one episodes of febrile neutropenia were analysed from the 36 patient records. Episode frequency ranged from 1 to 5. The mean duration of febrile neutropenic episodes was 5. 01 days (± SD 5. 2), with range from 1 - 25 days. Acute Lymphoblastic Leukaemia (ALL) accounted for 43. 7%. The mean WBC for the study population was 0. 88 x 10(9)/L (± SD 0. 61), with the mean absolute neutrophil count (ANC) at 0. 16 x 10(9)/L (± SD 0. 23). Antifungal therapy was used in 6 cases and the incidence of blood culture positive sepsis was 8. 5%. Complete resolution occurred in 65 episodes CONCLUSIONS: Febrile neutropenia episodes treated at the WFPH have a very favourable outcome (91. 5%). The further analysis of the relationships found in this study between the total white blood cell count at presentation and the duration of antimicrobial therapy, the duration of the febrile neutropenic episodes and outcome is needed.

OBJETIVO: Evaluar la incidencia, presentación, tratamiento y evolución clínica de los episodios neutropénicos febriles de pacientes tratados en el Hospital Pediátrico Wendy Fitzwilliam (WFPH) en Trinidad y Tobago. METODOLOGÍA: Mediante un método de cohorte retrospectivo, se analizaron las historias clínicas de todos los pacientes inscritos en la Unidad de Oncología Pediátrica en WFPH, que recibieron quimioterapia para el tratamiento de neoplasias hematológicas o tumores malignos sólidos desde mayo de 2001 a abril de 2008 y tuvieron episodios de neutropenia febril. RESULTADOS: Se analizaron setenta y un episodios de neutropenia febril de las historias clínicas de 36 pacientes. La frecuencia de los episodios osciló entre 1 y 5. La duración promedio de los episodios neutropénicos febriles fue 5. 01 días (± SD 5. 2), con un rango de 1 a 25 días. La leucemia linfoblástica aguda (LLA) representó el 43, 7% de los casos. El promedio del conteo de glóbulos blancos (WBC) para la población de estudio fue 0. 88 X 10(9)/L (± SD 0, 61), con el promedio del conteo absoluto de neutrófilos (CAN) en 0. 16 X 10(9)/L (± SD 0. 23). La terapia antifúngica fue utilizada en 6 casos y la incidencia de la sepsis confirmada por cultivo positivo de la sangre fue 8. 5%. En 65 episodios (91. 5%) hubo resolución completa con 6 muertes. CONCLUSIONES: Los episodios de neutropenia febril tratados en la WFPH tienen una evolución clínica muy favorable (91. 5%). Se necesita profundizar en el análisis de las relaciones encontradas en este estudio entre el conteo total de glóbulos blancos en la presentación y la duración del tratamiento con antibióticos, la duración de los episodios neutropénicos febriles y la evolución clínica.

Determination of angiotensin I-converting enzyme activity in equine blood: lack of agreement between methods of analysis

Angiotensin-I converting enzyme (ACE) is a key regulator of blood pressure, electrolytes and fluid homeostasis through conversion of angiotensin I into angiotensin II. Recently, a genetic polymorphism of the ACE gene, which accounts for 47% of the variation of ACE activity in blood, has been advocated as a biomarker of athletic aptitude. Different methods of analysis and determination of ACE activity in plasma have been used in human and equine research without a consensus of a "gold standard" method. Different methods have often been used interchangeably or cited as being comparable in the existing literature; however, the actual agreement between assays has not been investigated. Therefore, in this study, we evaluated the level of agreement between three different assays using equine plasma obtained from 29 horses. Two spectrophotometric assays using Furylacryloyl-phenylalanyl-glycyl-glycine as substrate and one fluorimetric assay utilizing o-aminobenzoic acid-FRK-(Dnp)P-OH were employed. The results revealed that the measurements from the different assays were not in agreement, indicating that the methods should not be used interchangeably for measurement of equine ACE activity. Rather, a single method of analysis should be adopted to achieve comparable results and critical appraisal of the literature is needed when attempting to compare results obtained from different assays.

Efficacy of different pharmacologic agents in reducing pain during propofol injection: a systematic review

Introduction: Propofol is a nonopioid intravenous anesthetic with a fast onset and short duration of action. It is commonly used as an induction agent, the sole agent in total intravenous anesthesia, or in short ambulatory procedures. One side effect of this drug is pain on injection. The pain on propofol injection can reach as much as 70%. Different pharmacologic interventions have been used to decrease propofol injection pain. The objective of this study is to determine the efficacy of different pharmacologic agents in reducing propofol injection pain. Materials and methods: A search for randomized controlled trials was done using electronic databases and manual searching. Letters were sent to anesthesiology departments nationwide for unpublished studies that may be included. Studies that met the inclusion criteria were appraised for methodological quality by two independent reviewers using the Physiotherapy Evidence database (PEDro) assessment tool. Meta-analysis was done using Review Manager (RevMan) Version 5.0 for Windows. Results: Sixteen studies were included in the review. Meta-analysis was done for lidocaine versus normal saline in decreasing propofol injection pain. Nineteen percent of patients complained of moderate pain and 7 percent complained of severe pain among those treated with lidocaine compared with 81% and 93%, respectively, among those given normal saline solution. the interventions not included in the meta-analysis were assessed based on the levels of evidence by Furlan. Conclusion: Lidocaine 40mg/IV given prior to propofol was efficacious in decreasing pain compared with normal saline solution. There is strong evidence for the use of remifentanil 0.01-0.02 mg or 2ug/kg as pretreatment in decreasing pain on propofol injection.

Prenatal MRI Findings of Fetuses with Congenital High Airway Obstruction Sequence

OBJECTIVE: To define the MRI findings of congenital high airway obstruction sequence (CHAOS) in a series of fetuses. MATERIALS AND METHODS: Prenatal fetal MR images were reviewed in seven fetuses with CHAOS at 21 to 27 weeks of gestation. The MRI findings were reviewed. The MRI parameters evaluated included the appearance of the lungs and diaphragm, presence or absence of hydrops, amount of amniotic fluid, airway appearance, predicted level of airway obstruction, and any additional findings or suspected genetic syndromes. RESULTS: All the fetuses viewed (7 of 7) demonstrated the following MRI findings: dilated airway below the level of obstruction, increased lung signal, markedly increased lung volumes with flattened or inverted hemidiaphragms, massive ascites, centrally positioned and compressed heart, as well as placentomegaly. Other frequent findings were anasarca (6 of 7) and polyhydramnios (3 of 7). MRI identified the level of obstruction as laryngeal in five cases and tracheal in two cases. In four of the patients, surgery or autopsy confirmed the MRI predicted level of obstruction. Associated abnormalities were found in 4 of 7 (genetic syndromes in 2). Postnatal radiography (n = 3) showed markedly hyperinflated lungs with inverted or flattened hemidiaphragms, strandy perihilar opacities, pneumothoraces and tracheotomy. Two fetuses were terminated and one fetus demised in utero. Four fetuses were delivered via ex utero intrapartum treatment procedure. CONCLUSION: MRI shows a consistent pattern of abnormalities in fetuses with CHAOS, accurately identifies the level of airway obstruction, and helps differentiate from other lung abnormalities such as bilateral congenital pulmonary airway malformation by demonstrating an abnormally dilated airway distal to the obstruction.

Anti-thrombosis effect and its mechanism of Qingkailing injection / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the anti-thrombosis effect and its mechanism of Qingkailing injection (QKL).</p><p><b>METHOD</b>SD rats were randomly divided into control group, model group and QKL 2.5, 5.0, 10 groups. QKL were given (i.p.) to rats once a day for successively 4 days. The rats in all groups but control were pretreated with carrageenin (Ca) i.p. at 16 h before the last dose of QKL and followed by intravenous injection of endotoxin ( LPS fom E. coli O111:B4) 50 microg x kg(-1) 30 min after the last dosing of QKL. Thrombosis in rat tails were observed at 24 h after injection of LPS. The number of white blood cells and platelets, serum TNF-alpha, IL-6 level, CD11b/CD18 expression of white blood cells and platelet aggregation were analysed.</p><p><b>RESULT</b>QKL obviously inhibited the LPS/Ca-induced thrombosis as showed a reduced infarction range due to thrombosis in tails. The sera concentration of TNF-alpha and IL-6, expression of CD11b/CD18 in WBC and platelet coagulation rate were reduced after QKL treatment.</p><p><b>CONCLUSION</b>The anti-thrombosis action of QKL is associated with inhibition of WBC activation and adherence, reduction of inflammatory factor release and abating of platelet coagulation rate. The anti-thrombosis mechanism of QKL is consistent with its function of clearing away heat-evil and toxic materials.</p>