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1.
Med J Malaysia ; 78(2): 241-249, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36988537

RESUMEN

INTRODUCTION: Time is the greatest challenge in stroke management. This study aimed to examine factors contributing to prehospital delay and decision delay among stroke patients. MATERIALS AND METHODS: A cross-sectional study involving acute stroke patients admitted to Seri Manjung Hospital was conducted between August 2019 and October 2020 via faceto- face interview. Prehospital delay was defined as more than 120 minutes taken from recognition of stroke symptoms till arrival in hospital, while decision delay was defined as more than 60 minutes taken from recognition of stroke symptoms till decision was made to seek treatment. RESULTS: The median prehospital delay of 102 enrolled patients was 364 minutes (IQR 151.5, 1134.3) while the median for decision delay was 120 minutes (IQR 30.0, 675.0). No history of stroke (adj. OR 4.15; 95% CI 1.21, 14.25; p=0.024) and unaware of thrombolysis service (adj. OR 17.12; 95% CI 1.28, 229.17; p=0.032) were associated with higher odds of prehospital delay, while Indian ethnicity (adj. OR 0.09; 95% CI 0.02, 0.52; p=0.007) was associated with lower odds of prehospital delay as compared to Malay ethnicity. On the other hand, higher National Institutes of Health Stroke Scale (NIHSS) score (adj. OR 0.86; 95% CI 0.78, 0.95; p=0.002) was associated with lower odds of decision delay. CONCLUSION: Public awareness is crucial to shorten prehosital delay and decision delay for better patients' outcomes in stroke. Various public health campaigns are needed to improve the awareness for stroke.


Asunto(s)
Servicios Médicos de Urgencia , Accidente Cerebrovascular , Humanos , Malasia , Hospitales de Distrito , Estudios Transversales , Factores de Tiempo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia
2.
Br Poult Sci ; 63(2): 142-149, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34423692

RESUMEN

1. In recent months, several outbreaks with clinical signs of MDV-1 were reported in Iranian parent and laying hen farms, in addition to backyard chickens. Several meq gene sequences from these outbreaks were amplified and molecularly characterised.2. The meq protein sequences revealed three different sizes, namely the standard 339 aa, a shorter form of 338 aa lacking a proline residue at position 191, and a very short (vs) size of 265 aa. Based on sequence and size, the 265 aa meq has never been reported from international research groups before. The protein has only one PPPP repeat motif suggesting it belongs to a highly virulent strain.3. The standard meq sequences showed 100% BLAST identity to the vv+ isolate Polen5. However, the 338 aa form clustered to the clade usually reported from North America.4. This is the first report on genetic analysis of MDV-1 from Iran, but further study is required to obtain a better picture of the diversity and prevalence of different MDV-1 strains circulating in the country's farms, backyard poultry and other bird species.


Asunto(s)
Herpesvirus Gallináceo 2 , Enfermedad de Marek , Enfermedades de las Aves de Corral , Animales , Pollos , Femenino , Herpesvirus Gallináceo 2/genética , Irán/epidemiología , Enfermedad de Marek/epidemiología , Enfermedades de las Aves de Corral/epidemiología
3.
J Intern Med ; 289(3): 293-308, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32910532

RESUMEN

Clostridioides (Clostridium) difficile (C. difficile) infection is one of the most common causes of increased morbidity and mortality. Approximately 500 000 C. difficile infections (CDIs) occur each year in the United States, and they result in more than 29 000 deaths. Patients with haematologic diseases are at a higher risk for this infection due to frequent hospitalization and exposure to treatment-associated risk factors. Whilst several currently available antimicrobial agents offer resolution, recurrence of infection remains a major concern. Recent advancement in deciphering C. difficile virulence mechanisms and identification of its allies in contributing to the infection has led to the development of alternative treatment strategies. Here, we will provide a contemporary discussion of how major risk factors in haematologic diseases, such as immunosuppression, chemoradiation, use of antibiotic, proton pump inhibitor and opioid, and deficiency in butyrate and antimicrobial peptides contribute to C. difficile infection. Next, we will highlight different approaches to control and mitigate this infection such as antibiotic stewardship and faecal microbiota transplantation. Finally, we will explore several emerging treatments such as use of pre- and probiotics, immunotherapy and microbiome-sparing agents.


Asunto(s)
Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/etiología , Enfermedades Hematológicas/complicaciones , Clostridioides difficile/patogenicidad , Microbioma Gastrointestinal , Hospitalización , Humanos , Factores de Riesgo , Virulencia
4.
J Intern Med ; 290(1): 40-56, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33372309

RESUMEN

Cancer treatment options have evolved to include immunotherapy and targeted therapy, in addition to traditional chemoradiation. Chemoradiation places the patient at a higher risk of infection through a myelosuppressive effect. High clinical suspicion and early use of antimicrobials play a major role in decreasing any associated morbidity and mortality. This has led to a widespread use of antimicrobials in cancer patients. Antimicrobial use, however, does not come without its perils. Dysbiosis caused by antimicrobial use affects responses to chemotherapeutic agents and is prognostic in the development and severity of certain cancer treatment-related complications such as graft-versus-host disease and Clostridioides difficile infections. Studies have also demonstrated that an intact gut microbiota is essential in the anticancer immune response. Antimicrobial use can therefore modulate responses and outcomes with immunotherapy targeting immune checkpoints. In this review, we highlight the perils associated with antimicrobial use during cancer therapy and the importance of a more judicious approach. We discuss the nature of the pathologic changes in the gut microbiota resulting from antimicrobial use. We explore the effect these changes have on responses and outcomes to different cancer treatment modalities including chemotherapy and immunotherapy, as well as potential adverse clinical consequences in the setting of stem cell transplant.


Asunto(s)
Antibacterianos/efectos adversos , Antineoplásicos/uso terapéutico , Disbiosis/inducido químicamente , Microbioma Gastrointestinal/efectos de los fármacos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia , Inflamación/fisiopatología , Neoplasias/fisiopatología
5.
Eur Cell Mater ; 41: 216-232, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33644848

RESUMEN

Conventional root canal treatment replaces the infected pulp with defined materials. Alternative cell-based tissue engineering strategies aim to regenerate a fully functional pulp within the root canal. Despite recent advances in this area, however, the regeneration of an innervated pulp remains a major challenge in the field. Both graphene (2DG) and pulsed electromagnetic fields (PEMFs) independently have been shown to promote diverse cellular developmental programs. The present study showed that 2DG promoted the neurogenic induction of human dental pulp stem cells (hDPSCs) by upregulating and accelerating the expression of mature neuronal markers. Notably, 2DG induced the highest expression of transient receptor potential canonical cation channel type 1 (TRPC1) during early neurogenesis. As brief PEMF exposure promotes in vitro differentiation by activating a TRPC1-mitochondrial axis, an opportunity to combine 2DG with developmentally targeted PEMF exposure for synergistic effects was realizable. Neurogenic gene expression, neurotransmitter release, and reactive oxygen species (ROS) production were greatly enhanced by a brief (10 min) and low amplitude (2 mT) PEMF exposure timed to coincide with the highest TRPC1 expression from hDPSCs on 2DG. In contrast, hDPSCs on glass were less responsive to PEMF exposure. The capacity of PEMFs to promote neurogenesis was precluded by the administration of penicillin/streptomycin, mirroring previous studies demonstrating that aminoglycoside antibiotics block TRPC1-mediated calcium entry and verifying the contribution of TRPC1 in this form of magnetoreception. Hence, graphene created a more conducive environment for subsequent PEMF-stimulated neurogenic induction of hDPSCs through their mutual capacity to activate TRPC1with subsequent ROS production.


Asunto(s)
Pulpa Dental/citología , Grafito/química , Neurogénesis/fisiología , Células Madre/citología , Canales Catiónicos TRPC/metabolismo , Diferenciación Celular/fisiología , Línea Celular , Proliferación Celular/fisiología , Pulpa Dental/metabolismo , Campos Electromagnéticos , Humanos , Regeneración/fisiología , Células Madre/metabolismo , Ingeniería de Tejidos/métodos
6.
BMC Plant Biol ; 20(1): 167, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32293285

RESUMEN

BACKGROUND: Deoxyxylulose 5-phosphate synthase (DXS) and deoxyxylulose 5-phosphate reductoisomerase (DXR) are the enzymes that catalyze the first two enzyme steps of the methylerythritol 4-phosphate (MEP) pathway to supply the isoprene building-blocks of carotenoids. Plant DXR and DXS enzymes have been reported to function differently depending on the plant species. In this study, the differential roles of rice DXS and DXR genes in carotenoid metabolism were investigated. RESULTS: The accumulation of carotenoids in rice seeds co-expressing OsDXS2 and stPAC was largely enhanced by 3.4-fold relative to the stPAC seeds and 315.3-fold relative to non-transgenic (NT) seeds, while the overexpression of each OsDXS2 or OsDXR caused no positive effect on the accumulation of either carotenoids or chlorophylls in leaves and seeds, suggesting that OsDXS2 functions as a rate-limiting enzyme supplying IPP/DMAPPs to seed carotenoid metabolism, but OsDXR doesn't in either leaves or seeds. The expressions of OsDXS1, OsPSY1, OsPSY2, and OsBCH2 genes were upregulated regardless of the reductions of chlorophylls and carotenoids in leaves; however, there was no significant change in the expression of most carotenogenic genes, even though there was a 315.3-fold increase in the amount of carotenoid in rice seeds. These non-proportional expression patterns in leaves and seeds suggest that those metabolic changes of carotenoids were associated with overexpression of the OsDXS2, OsDXR and stPAC transgenes, and the capacities of the intermediate biosynthetic enzymes might be much more important for those metabolic alterations than the transcript levels of intermediate biosynthetic genes are. Taken together, we propose a 'Three Faucets and Cisterns Model' about the relationship among the rate-limiting enzymes OsDXSs, OsPSYs, and OsBCHs as a "Faucet", the biosynthetic capacity of intermediate metabolites as a "Cistern", and the carotenoid accumulations as the content of "Cistern". CONCLUSION: Our study suggests that OsDXS2 plays an important role as a rate-limiting enzyme supplying IPP/DMAPPs to the seed-carotenoid accumulation, and rice seed carotenoid metabolism could be largely enhanced without any significant transcriptional alteration of carotenogenic genes. Finally, the "Three Faucets and Cisterns model" presents the extenuating circumstance to elucidate rice seed carotenoid metabolism.


Asunto(s)
Isomerasas Aldosa-Cetosa/fisiología , Carotenoides/metabolismo , Eritritol/análogos & derivados , Oryza/enzimología , Fosfatos de Azúcar/fisiología , Isomerasas Aldosa-Cetosa/genética , Butadienos/síntesis química , Butadienos/metabolismo , Eritritol/genética , Eritritol/fisiología , Hemiterpenos/síntesis química , Hemiterpenos/metabolismo , Hojas de la Planta/enzimología , Semillas/enzimología , Fosfatos de Azúcar/genética , Transferasas/genética , Transferasas/fisiología
7.
Med J Malaysia ; 75(6): 742-744, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33219189

RESUMEN

Methicillin-resistant Staphylococcus aureus (MRSA) purulent pericarditis, characterised by frank pus collection or microscopic pyogenic effusion in the pericardium represents the most serious form of pericardial infection. The route of MRSA acquisition in pericardial abscess commonly occurs via the blood stream infection and it is more commonly observed among immunocompromised individuals. To date, diabetic foot ulcer infection rarely disseminates and becomes a nidus for pericardial infection. Herein, we report an unusual case of MRSA pericardial abscess in a 44-year-old man who presented at Hospital Seri Manjung, Malaysia with cardiac tamponade. Past medical history indicated that he was recently treated for infected diabetic foot ulcer with MRSA bacteraemia one week earlier. Despite adequate pericardial drainage and extended parenteral vancomycin therapy, this case ended in fatality on day 42 of admission due to nosocomial infection. It is hoped that this report serves to increase the vigilance among clinicians that diabetic foot ulcer infections have the potential to progress to pericardial abscess in the presence of MRSA bacteraemia, although they may appear seemingly innocuous at presentation. Systemic vancomycin must be instituted promptly when MRSA bacteraemia is confirmed in order to circumvent the propagation of MRSA.


Asunto(s)
Diabetes Mellitus , Pie Diabético , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Absceso/tratamiento farmacológico , Absceso/etiología , Adulto , Antibacterianos/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Pie Diabético/complicaciones , Humanos , Masculino , Pericardio , Infecciones Estafilocócicas/tratamiento farmacológico
8.
Public Health ; 173: 5-8, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31207425

RESUMEN

OBJECTIVE: The objective of this study was to explore factors influencing patients with hypertension to participating in a hypertension self-management education (HSME) programme and challenges of sustaining the learnt self-care practices. STUDY DESIGN: This was a qualitative study with focus group discussions. METHODS: Focus group discussions using a semistructured moderator guide were conducted among participants who had attended the HSME programme. Data were audio recorded, transcribed verbatim and analysed using a thematic analysis approach. RESULTS: Three focus groups involving 19 participants were conducted. Four major themes emerged from the data collected. Most participants enjoyed the group-based HSME sessions because sharing experiences with those having similar health problems can reduce their sense of isolation. However, the participants highlighted the difficulty in sustaining self-care practices in the presence of friends and family influences. CONCLUSION: A number of patient-, family- and community-level motivators and barriers to patients' hypertension self-management have been identified. Efforts to tailor behavioural interventions to sustain daily self-care activities during social and cultural events are imperative.


Asunto(s)
Educación en Salud , Conocimientos, Actitudes y Práctica en Salud , Hipertensión/terapia , Motivación , Educación del Paciente como Asunto , Autocuidado/psicología , Automanejo/psicología , Anciano , Femenino , Grupos Focales , Humanos , Hipertensión/psicología , Masculino , Persona de Mediana Edad , Investigación Cualitativa
9.
Med J Malaysia ; 74(6): 472-476, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31929471

RESUMEN

INTRODUCTION: Melioidosis is caused by Burkholderia pseudomallei, a gram-negative aerobic bacillus, found in the soil and surface water. Treating melioidosis has been a challenge in district hospitals due to high usage of broad spectrum antibiotics and prolonged hospitalisation. This study is to review the patients' demography, clinical presentations and microbiological data. METHODS: A 5-year retrospective study was carried out on patients admitted with culture positive for melioidosis from year 2013 to 2017 in Hospital Teluk Intan, Perak. RESULTS: There were a total of 46 confirmed cases of melioidosis. Majority of the patients were working in the agricultural and farming (28.6%), and factories (25.7%). Thirty-one patients had diabetes mellitus (71.1%). Presentations of patients with melioidosis included pneumonia (54.3%), skin and soft tissue infection (19.6%), deep abscesses (15.2%) and bone and joint infections (13%). An average of 5.8 days was needed to confirm the diagnosis of melioidosis via positive culture. However, only 39.4% of these patients were started on ceftazidime or carbapenem as the empirical therapy. The intensive care unit (ICU) admission rate for melioidosis was 46% and the mortality rate was 52%. Our microbial cultures showed good sensitivity towards cotrimoxazole (97.1%), ceftazidime (100%) and carbapenem (100%). CONCLUSION: Melioidosis carries high mortality rate, especially with lung involvement and bacteremia. Physicians should have high clinical suspicion for melioidosis cases to give appropriate antimelioidosis therapy early.


Asunto(s)
Bacteriemia/tratamiento farmacológico , Ceftazidima/uso terapéutico , Hospitales de Distrito/estadística & datos numéricos , Melioidosis/tratamiento farmacológico , Adulto , Antibacterianos/uso terapéutico , Bacteriemia/epidemiología , Bacteriemia/microbiología , Burkholderia pseudomallei/aislamiento & purificación , Femenino , Estudios de Seguimiento , Hospitalización/tendencias , Humanos , Incidencia , Malasia/epidemiología , Masculino , Melioidosis/epidemiología , Melioidosis/microbiología , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
10.
Eur J Neurol ; 25(9): 1177-1181, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29772097

RESUMEN

BACKGROUND AND PURPOSE: Although studies have evaluated the relationship between intravitreal bevacizumab (IVB) injection and cerebral infarction (CI), the effects of IVB on CI are still not clear. The aim of this study was to investigate the effects of IVB injection on patients with CI with age-related macular degeneration (AMD). METHODS: We retrospectively reviewed patients with AMD who received IVB injections for 1 year and determined the incidence of CI within 60 days after IVB injection to analyze the possible association between IVB and CI. RESULTS: A total of 263 patients were enrolled over a 12-month period. Six patients (2.28%) were diagnosed with CI within 2 months after receiving an IVB injection. The incidence of CI in patients of 75-84 years of age was 6.38%. These results showed a higher incidence for patients with IVB injections than the results of previous epidemiological studies (0.13% for all age groups, 1.68% for patients of 75-84 years of age). All CIs occurred 21-53 days after the IVB injection (mean: 39.33 ± 14.65 days). Logistic regression analyses showed that age and CI history were factors associated with CI. CONCLUSIONS: Treatment with IVB might be an independent risk factor for CI. These results are useful for planning treatment strategies for patients with AMD and for prevention of CI.


Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/administración & dosificación , Bevacizumab/efectos adversos , Infarto Cerebral/inducido químicamente , Anciano , Anciano de 80 o más Años , Bevacizumab/uso terapéutico , Infarto Cerebral/epidemiología , Estudios Transversales , Femenino , Humanos , Incidencia , Inyecciones Intravítreas , Degeneración Macular/complicaciones , Degeneración Macular/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/inducido químicamente , Accidente Cerebrovascular/epidemiología
11.
Ann Oncol ; 28(9): 2199-2205, 2017 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-28911074

RESUMEN

BACKGROUND: Current standard treatment, including non-anthracycline-based chemotherapy and optimal combining of radiotherapy, has dramatically improved outcomes of patients with extranodal natural killer/T-cell lymphoma (ENKTL) during the last decade. This study was conducted to investigate the clinical outcome of ENKTL patients with relapsed or progressive disease after initial current standard therapy. PATIENTS AND METHODS: We retrospectively reviewed patients diagnosed with ENKTL at six centers in four countries (China, France, Singapore, and South Korea) from 1997 to 2015 and analyzed 179 patients who had relapsed or progressed after initial current standard therapy. RESULTS: After a median follow-up of 58.6 months (range 27.9-89.2), the median second progression-free survival (PFS) was 4.1 months [95% confidence interval (CI) 3.04-5.16] and overall survival (OS) was 6.4 months (95% CI 4.36-8.51). Multivariate Cox-regression analysis revealed that elevated lactate dehydrogenase, multiple extranodal sites (≥2), and presence of B symptoms were associated with inferior OS (P < 0.05). OS and PFS were significantly different according to both prognostic index of natural killer lymphoma (PINK) and PINK-E (Epstein-Barr virus) models. Salvage chemotherapy with l-asparaginase (l-Asp)-based regimens showed a significantly better clinical benefit to response rate and PFS, although it did not lead to OS improvement. First use of l-Asp in the salvage setting and l-Asp rechallenge at least 6 months after initial treatment were the best candidates for salvage l-Asp containing chemotherapy. CONCLUSIONS: Most patients with relapsed or refractory ENKTL had poor prognosis with short survival. Further studies are warranted to determine the optimal treatment of patients with relapsed or refractory ENKTL.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antraciclinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Progresión de la Enfermedad , Femenino , Humanos , Linfoma Extranodal de Células NK-T/patología , Masculino , Persona de Mediana Edad , Recurrencia , Terapia Recuperativa , Resultado del Tratamiento , Adulto Joven
13.
Cancer Metastasis Rev ; 33(2-3): 747-56, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24817039

RESUMEN

Circulating tumour cells (CTCs) are emerging as important prognostic markers and have potential clinical utility as tumour biomarkers for targeted cancer therapy. Although CTCs were proposed more than 100 years ago as potential precursors that may form metastatic lesions, formal evidence that CTCs are indeed capable of initiating metastases is limited. Moreover, the process of CTCs shedding into the circulation, relocating to distant organ sites and initiating metastatic foci is complex and intrinsically inefficient. To partially explain the metastatic process, the concepts of CTCs as metastatic precursors or pre-metastatic conditioners have been proposed; however, it is questionable as to whether these are both variable pathways to metastasis or just markers of metastatic burden. This review explores the evidence for CTCs in the initiation and progression of metastatic cancer and the data supporting these different concepts in an attempt to better understand the role of CTCs in metastasis. A greater understanding of the metastatic potential of CTCs will open new avenues for therapeutic interventions in the future.


Asunto(s)
Neoplasias/patología , Células Neoplásicas Circulantes , Animales , Humanos , Metástasis de la Neoplasia , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/mortalidad , Microambiente Tumoral
14.
Br J Cancer ; 113(10): 1421-6, 2015 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-26505681

RESUMEN

BACKGROUND: The purpose of this randomised phase III trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3methyglutaryl coenzyme A reductase inhibitor, to XELIRI/FOLFIRI chemotherapy regimens confers a clinical benefit to patients with previously treated metastatic colorectal cancer. METHODS: We undertook a double-blind, placebo-controlled phase III trial of 269 patients previously treated for metastatic colorectal cancer and enrolled in 5 centres in South Korea. Patients were randomly assigned (1:1) to one of the following groups: FOLFIRI/XELIRI plus simvastatin (40 mg) or FOLFIRI/XELIRI plus placebo. The FOLFIRI regimen consisted of irinotecan at 180 mg m(-2) as a 90-min infusion, leucovorin at 200 mg m(-2) as a 2-h infusion, and a bolus injection of 5-FU 400 mg m(-2) followed by a 46-h continuous infusion of 5-FU at 2400 mg m(-2). The XELIRI regimen consisted of irinotecan at 250 mg m(-2) as a 90-min infusion with capecitabine 1000 mg m(-2) twice daily for 14 days. The primary end point was progression-free survival (PFS). Secondary end points included response rate, duration of response, overall survival (OS), time to progression, and toxicity. RESULTS: Between April 2010 and July 2013, 269 patients were enrolled and assigned to treatment groups (134 simvastatin, 135 placebo). The median PFS was 5.9 months (95% CI, 4.5-7.3) in the XELIRI/FOLFIRI plus simvastatin group and 7.0 months (95% CI, 5.4-8.6) in the XELIRI/FOLFIRI plus placebo group (P=0.937). No significant difference was observed between the two groups with respect to OS (median, 15.9 months (simvastatin) vs 19.9 months (placebo), P=0.826). Grade⩾3 nausea and anorexia were noted slightly more often in patients in the simvastatin arm compared with with the placebo arm (4.5% vs 0.7%, 3.0% vs 0%, respectively). CONCLUSIONS: The addition of 40 mg simvastatin to the XELIRI/FOLFIRI regimens did not improve PFS in patients with previously treated metastatic colorectal cancer nor did it increase toxicity.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Simvastatina/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Capecitabina/administración & dosificación , Capecitabina/uso terapéutico , Método Doble Ciego , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Irinotecán , Leucovorina/administración & dosificación , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , República de Corea , Simvastatina/efectos adversos , Simvastatina/uso terapéutico , Análisis de Supervivencia , Resultado del Tratamiento
15.
Ann Oncol ; 26(4): 762-768, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25538174

RESUMEN

BACKGROUND: It is unclear whether treating brain metastasis before starting systemic chemotherapy can improve survival compared with upfront chemotherapy in non-small-cell lung cancer (NSCLC) with asymptomatic cerebral oligo-metastases. PATIENTS AND METHODS: We undertook a randomized, controlled trial of 105 patients with one to four brain metastases, admitted to Samsung Medical Center between 2008 and 2013. Patients were randomly assigned to receive stereotactic radiosurgery (SRS) (49 patients) followed by chemotherapy or upfront chemotherapy (49 patients). The primary end point was overall survival (OS) and secondary end points included central nervous system (CNS) progression-free survival, progression to symptomatic brain metastasis and brain functional outcome. RESULTS: The median age was 58 years (range, 29-85) with ECOG 0-1 performance status, and 40% of patients were never smokers. Most patients had adenocarcinoma, and about half of patients had only one brain metastasis, while the rest had multiple cerebral metastases. The median OS time was 14.6 months [95% confidence interval (CI), 9.2-20.0] in the SRS group and 15.3 months (95% CI, 7.2-23.4) for the upfront chemotherapy group (P = 0.418). There was no significant difference in time to CNS disease progression [median, 9.4 months (SRS) versus 6.6 months (upfront chemotherapy), P = 0.248]. Symptomatic progression of brain metastases was observed more frequently in the upfront chemotherapy group (26.5%) than the SRS group (18.4%) but without statistical significance. CONCLUSIONS: Although this study included smaller sample size than initially anticipated due to early termination, SRS followed by chemotherapy did not improve OS in oligo-brain metastases NSCLC patients compared with upfront chemotherapy. Further study with large number of patients should be needed to confirm the use of upfront chemotherapy alone in this subgroup of patients. CLINICAL TRIALS NUMBER: NCT01301560.


Asunto(s)
Adenocarcinoma/cirugía , Neoplasias Encefálicas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Radiocirugia , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia
17.
Pharmacogenomics J ; 14(4): 316-21, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24394201

RESUMEN

To study the possible genetic associations with adverse drug reactions (ADR), the Singapore Health Sciences Authority (HSA) has piloted a program to collect DNA and phenotype data of ADR cases as part of its pharmacovigilance program. Between 2009 and 2012, HSA screened 158 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). To assess the association between HLA-B*1502 and carbamazepine (CBZ)-induced SJS/TEN, 13 cases and 26 drug-tolerant controls were analyzed. All 13 CBZ-SJS/TEN cases and 3/26 controls were HLA-B*1502 positive (odds ratio 181, 95% confidence interval: 8.7-3785, P=6.9 × 10(-8)). Discussions of the finding with the Ministry of Health and an expert panel led to the decision to make HLA-B*1502 testing the standard of care prior to first use of CBZ in Asians and to subsidize the genotyping test at public hospitals. This program illustrates the role of a regulatory authority in advancing the use of pharmacogenetics for drug safety.


Asunto(s)
Carbamazepina/efectos adversos , Exantema/inducido químicamente , Farmacogenética , Farmacovigilancia , Adulto , Alelos , Estudios de Casos y Controles , Genotipo , Antígenos HLA-B/genética , Humanos , Persona de Mediana Edad , Farmacogenética/métodos , Proyectos Piloto , Singapur , Síndrome de Stevens-Johnson/etiología
18.
J Appl Microbiol ; 116(5): 1119-28, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24779580

RESUMEN

AIM: The aim of this study was to investigate the mode of action of the lavender essential oil (LV) on antimicrobial activity against multi-drug-resistant Escherichia coli J53 R1 when used singly and in combination with piperacillin. METHOD AND RESULTS: In the time-kill analysis, a complete killing of bacteria was observed based on colony counts within 4 h when LV was combined with piperacillin during exposure at determined FIC concentrations. Analysis of the membrane permeabilizing effects of LV on treated cultures through their stability against sodium dodecyl sulphate revealed that the LV played a role in disrupting the bacterial cell membrane. The finding is further supported by scanning electron microscopy analysis and zeta potential measurement. In addition, reduction in light production expression of E. coli [pSB1075] by the LV showed the presence of potential quorum sensing (QS) inhibitors. CONCLUSIONS: These results indicated that the LV has the potential to reverse bacterial resistance to piperacillin in E. coli J53 R1. It may operate via two mechanisms: alteration of outer membrane permeability and inhibition of bacterial QS. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings offer a novel approach to develop a new option of phytopharmaceuticals against multi-drug-resistant E. coli.


Asunto(s)
Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Permeabilidad de la Membrana Celular/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple , Sinergismo Farmacológico , Escherichia coli/genética , Escherichia coli/ultraestructura , Lavandula , Aceites Volátiles/química , Aceites de Plantas/química , Plásmidos/genética , Percepción de Quorum/efectos de los fármacos
19.
Clin Radiol ; 69(4): 416-23, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24457015

RESUMEN

AIM: To investigate the dark choledochal ring sign on T2-weighted imaging (T2WI) as an indicator for pancreatic ductal adenocarcinoma (PDAC) among periampullary carcinomas. MATERIALS AND METHODS: Sixty patients with surgically confirmed periampullary cancers [30 PDACs, 15 distal common bile duct (CBD) cancers, 13 ampullary cancers, and two duodenal cancers] who underwent liver magnetic resonance imaging (MRI) were included in this study. Two reviewers independently evaluated unenhanced and gadoxetic acid-enhanced MRI (T1WI image set), and a combined T2WI and T1WI image set for differentiation between PDAC and other periampullary carcinomas using a rating scale, and the presence of the dark choledochal ring sign on T2WI, for all 60 tumours. RESULTS: In PDAC, the dark choledochal ring sign on T2WI was considered positive in 23 cases by observer 1 and 24 cases by observer 2, but only in one or two CBD cancers, as determined by each observer, respectively. This resulted in sensitivities of 76.7% and 80% and specificities of 96.7% and 93.3% for observer 1 and 2, respectively, in the diagnosis of PDAC. Adding T2WI correctly led to a change of diagnosis in three and four cases of PDAC by each observer, respectively. Thus, there were significant differences between the two image sets for both observers in distinguishing between PDAC and other periampullary carcinomas (p = 0.02). CONCLUSION: The presence of the dark choledochal ring sign on axial T2WI could be a complementary imaging feature indicative of PDAC to differentiate PDAC from other periampullary carcinomas at MRI.


Asunto(s)
Adenocarcinoma/diagnóstico , Artefactos , Conducto Colédoco/patología , Imagen por Resonancia Magnética , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adulto , Anciano , Medios de Contraste , Diagnóstico Diferencial , Femenino , Gadolinio DTPA , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/patología , Prevalencia , Pronóstico , Reproducibilidad de los Resultados , República de Corea/epidemiología , Estudios Retrospectivos , Sensibilidad y Especificidad
20.
Anaesthesist ; 63(2): 122-8, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24499959

RESUMEN

AIM: The aim of the present study was to determine (1) whether successful intraoperative electromyography monitoring for lateral spread response (LSR) is possible with partial neuromuscular blockade (NMB) in subjects undergoing microvascular decompression (MVD) for hemifacial spasm and (2) the adequate level of NMB to achieve that goal. MATERIAL AND METHODS: A total of 61 patients in whom LSR was monitored during MVD were enrolled in the study. Patients were randomly allocated to two groups: group TOF in which the NMB target was maintenance of two train-of-four (TOF) counts and group T1 in which the NMB target was maintenance of a T1/Tc ratio of 50 % (T1: first twitch height of TOF and Tc: control twitch height). The adductor pollicis brevis muscle was used to monitor TOF responses. The frequency of successful LSR monitoring, defined as successful baseline establishment and maintenance of LSR until surgical decompression, was compared between the two groups. RESULTS: Of the 61 patients 2 were excluded from the study so that 30 patients in group TOF and 29 patients in group T1 were analyzed. The success rate of LSR monitoring was clinically acceptable and significantly higher in group T1 than in group TOF, i.e. n = 15 (50.0 %) in group TOF versus n = 24 (82.8 %) in group T1 (P = 0.008), corresponding to a 32.8 % higher success rate in group T1 than group TOF (95 % CI: 13.9-51.7 %). Mean vecuronium infusion dose was smaller and mean TOF count was higher in group T1 than group TOF with a TOF count = 2 (1) in group TOF versus 3 (1) in group T1 (P = 0.003). Mean sevoflurane and remifentanil infusion doses were not different between groups. There was no incidence of spontaneous movement during microscopy in either group. CONCLUSION: Maintenance of partial NMB with a target T1/Tc ratio of 50 % resulted in a clinically acceptable success rate of LSR monitoring and surgical condition during MVD. Maintenance of partial NMB with a target T1/Tc ratio of 50 % rather than TOF count of two during LSR monitoring for MVD can therefore be recommended.


Asunto(s)
Espasmo Hemifacial/cirugía , Cirugía para Descompresión Microvascular/métodos , Bloqueo Neuromuscular , Bloqueantes Neuromusculares/farmacología , Adulto , Anciano , Anestesia General , Anestésicos por Inhalación , Anestésicos Intravenosos , Estimulación Eléctrica , Electromiografía , Nervio Facial/cirugía , Femenino , Humanos , Masculino , Éteres Metílicos , Persona de Mediana Edad , Monitoreo Intraoperatorio , Bloqueantes Neuromusculares/farmacocinética , Fármacos Neuromusculares no Despolarizantes , Piperidinas , Remifentanilo , Sevoflurano , Resultado del Tratamiento , Bromuro de Vecuronio
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