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1.
Poult Sci ; 103(2): 103323, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38103530

RESUMO

The current study aimed to determine the effects of different levels of fermented Juncao grass (FG) on growth parameters, blood constituents, immunity, and antioxidative properties of broilers. A total of 240 (21-d-old) broiler chicks were randomly distributed to four dietary treatments of sixty birds, with six replicate pens and ten birds in each. Fermented grass was added to the basal diet at four levels with 0, 5, 10, and 15% FG. The results revealed that broilers fed 5% FG had significantly higher (P < 0.05) final body weight (FBW), average daily gain (WG) and average daily feed intake (ADFI). The best conversion ratio (FCR) was recorded for broilers supplemented with 5% FG compared to the group supplemented with 15% FG (P < 0.05). Increasing FG % decreased (P < 0.05) anti-inflammatory cytokines IL-4, IL-6, and IL-10. However, FG increased (P < 0.05) proinflammatory cytokines IFN-γ, IL-1, IL-2, IL-12, and TNF-α (P < 0.05). Moreover, IgA, IgG, and IgM levels increased (P < 0.05) with increasing FG %. In addition, increasing FG % in broiler rations significantly increased (P < 0.05) serum antioxidant levels of T-AOC, GSH-PX, SOD, CAT, NO and GSH, but decreased (P < 0.05) MDA levels compared to the control group. Conclusively, fermented Juncao grass would be considered a novel herbal feed additive for improving broiler performance, immunity, antioxidant, and health status. Nevertheless, further research at the molecular level is needed to quantify the effects of these herbal components on cellular and humoral immune functions in broiler chickens.


Assuntos
Antioxidantes , Galinhas , Animais , Galinhas/fisiologia , Suplementos Nutricionais , Dieta/veterinária , Citocinas , Imunidade , Ração Animal/análise
2.
EClinicalMedicine ; 57: 101850, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36864983

RESUMO

Background: Malnutrition and obesity are interdependent pathologies along the same spectrum. We examined global trends and projections of disability-adjusted life years (DALYs) and deaths from malnutrition and obesity until 2030. Methods: Using data from the 2019 Global Burden of Disease study involving 204 countries and territories, trends in DALYs and deaths were described for obesity and malnutrition from 2000 to 2019, stratified by geographical regions (as defined by WHO) and Socio-Demographic Index (SDI). Malnutrition was defined according to the 10th revision of International Classification of Diseases codes for nutritional deficiencies, stratified by malnutrition type. Obesity was measured via body mass index (BMI) using metrics related to national and subnational estimates, defined as BMI ≥25 kg/m2. Countries were stratified into low, low-middle, middle, high-middle, and high SDI bands. Regression models were constructed to predict DALYs and mortality up to 2030. Association between age-standardised prevalence of the diseases and mortality was also assessed. Findings: In 2019, age-standardised malnutrition-related DALYs was 680 (95% UI: 507-895) per 100,000 population. DALY rates decreased from 2000 to 2019 (-2.86% annually), projected to fall 8.4% from 2020 to 2030. Africa and low SDI countries observed highest malnutrition-related DALYs. Age-standardised obesity-related DALY estimates were 1933 (95% UI: 1277-2640). Obesity-related DALYs rose 0.48% annually from 2000 to 2019, predicted to increase by 39.8% from 2020 to 2030. Highest obesity-related DALYs were in Eastern Mediterranean and middle SDI countries. Interpretation: The ever-increasing obesity burden, on the backdrop of curbing the malnutrition burden, is predicted to rise further. Funding: None.

3.
Metabolism ; 141: 155402, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36717058

RESUMO

BACKGROUND: A significant proportion of premature deaths globally are related to metabolic diseases in young adults. We examined the global trends and mortality of metabolic diseases in individuals aged below 40 years using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019. METHODS: From 2000 to 2019, global estimates of deaths and disability-adjusted life years (DALYs) were described for metabolic diseases (type 2 diabetes mellitus [T2DM], hyperlipidemia, hypertension, obesity, non-alcoholic fatty liver disease [NAFLD]). Subgroup analyses were performed based on sex, geographical regions and Socio-Demographic Index (SDI). Age-standardised death and DALYs were presented per 100,000 population with 95 % uncertainty intervals (UI). Projections of mortality and DALYs were estimated using regression models based on the GBD 2019 data and combining them with Institute for Health Metrics and Evaluation projection counts for years up to 2050. RESULTS: In 2019, the highest age-standardised death rates were observed in hypertension (133·88 [121·25-155·73]), followed by obesity (62·59 [39·92-89·13]), hyperlipidemia (56·51 [41·83-73·62]), T2DM (18·49 [17·18-19·66]) and NAFLD (2·09 [1·61-2·60]). Similarly, obesity (1932·54 [1276·61-2639·74]) had the highest age-standardised DALYs, followed by hypertension (2885·57 [2580·75-3201·05]), hyperlipidemia (1207·15 [975·07-1461·11]), T2DM (801·55 [670·58-954·43]) and NAFLD (53·33 [40·73-68·29]). Mortality rates decreased over time in hyperlipidemia (-0·6 %), hypertension (-0·47 %), NAFLD (-0·31 %) and T2DM (-0·20 %), but not in obesity (1·07 % increase). The highest metabolic-related mortality was observed in Eastern Mediterranean and low SDI countries. By 2050, obesity is projected to contribute to the largest number of deaths (102·8 % increase from 2019), followed by hypertension (61·4 % increase), hyperlipidemia (60·8 % increase), T2DM (158·6 % increase) and NAFLD (158·4 % increase), with males continuing to bear the greatest burden across all metabolic diseases. CONCLUSION: The growing burden of metabolic diseases, increasing obesity-related mortality trends, and the sex-regional-socioeconomic disparities evident in young adulthood, underlie the concerning growing global burden of metabolic diseases now and in future.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Masculino , Humanos , Adulto Jovem , Adulto , Idoso , Carga Global da Doença , Anos de Vida Ajustados por Qualidade de Vida , Sindemia , Fatores de Risco , Obesidade
6.
AJNR Am J Neuroradiol ; 43(1): 98-101, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34949591

RESUMO

Reports of a rare form of cerebral venous sinus thrombosis with profound thrombocytopenia have emerged following introduction of the adenovirus-vectored coronavirus disease 2019 (COVID-19) vaccines. Between March and June 2021, seven cases of refractory vaccine-induced immune thrombotic thrombocytopenia were referred to our institution for mechanical thrombectomy. The condition of 1 patient deteriorated during interhospital transfer, and the remaining 6 underwent successful recanalization. No procedure-related adverse events were reported. At the time of this writing, 3 patients have been discharged with a good functional outcome (mRS 0-1), one required rehabilitation for mild dysarthria and vocal cord palsy (mRS 3), and 2 have died due to severe mass effect. Our anecdotal experience suggests that endovascular therapy may be safe and effective in reducing thrombus burden in selected cases of postvaccination cerebral venous sinus thrombosis.


Assuntos
COVID-19 , Trombose dos Seios Intracranianos , Trombocitopenia , Trombose , Vacinas , Humanos , SARS-CoV-2 , Trombose dos Seios Intracranianos/diagnóstico por imagem , Trombectomia
7.
J Dent Res ; 100(10): 1030-1038, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34365857

RESUMO

Due to the severe mechano-biochemical conditions in the oral cavity, many dental restorations will degrade and eventually fail. For teeth restored with resin composite, the major modes of failure are secondary caries and fracture of the tooth or restoration. While clinical studies can answer some of the more practical questions, such as the rate of failure, fundamental understanding on the failure mechanism can be obtained from laboratory studies using simplified models more effectively. Reviewed in this article are the 4 main types of models used to study the degradation of resin-composite restorations, namely, animal, human in vivo or in situ, in vitro biofilm, and in vitro chemical models. The characteristics, advantages, and disadvantages of these models are discussed and compared. The tooth-restoration interface is widely considered the weakest link in a resin composite restoration. To account for the different types of degradation that can occur (i.e., demineralization, resin hydrolysis, and collagen degradation), enzymes such as esterase and collagenase found in the oral environment are used, in addition to acids, to form biochemical models to test resin-composite restorations in conjunction with mechanical loading. Furthermore, laboratory tests are usually performed in an accelerated manner to save time. It is argued that, for an accelerated multicomponent model to be representative and predictive in terms of both the mode and the speed of degradation, the individual components must be synchronized in their rates of action and be calibrated with clinical data. The process of calibrating the in vitro models against clinical data is briefly described. To achieve representative and predictive in vitro models, more comparative studies of in vivo and in vitro models are required to calibrate the laboratory studies.


Assuntos
Cárie Dentária , Dente , Animais , Biofilmes , Resinas Compostas , Restauração Dentária Permanente , Humanos
8.
J Laryngol Otol ; 135(3): 255-258, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33648615

RESUMO

BACKGROUND: There is a paucity of Asian-based data regarding the diagnostic yield of computed tomography imaging in the initial assessment of idiopathic unilateral vocal fold palsy. OBJECTIVES: To investigate the diagnostic yield of computed tomography in idiopathic unilateral vocal fold palsy cases in an Asian tertiary hospital, and to determine the causative pathologies and positive predictive factors. METHOD: A retrospective chart review was conducted of patients (between 2010 and 2018) with a clinical diagnosis of idiopathic unilateral vocal fold palsy who underwent contrast-enhanced computed tomography of the neck and chest at Tan Tock Seng Hospital, Singapore. RESULTS: The overall computed tomography diagnostic yield was 21 per cent, with malignancy accounting for 63.6 per cent of diagnoses. Degree of vocal fold weakness was the only significant predictor of positive computed tomography findings (11.5 per cent in vocal fold paresis vs 29.1 per cent in vocal fold paralysis, p = 0.025). None of the patients with negative computed tomography findings went on to develop disease after a mean follow up of 14.3 months. CONCLUSION: Computed tomography is a useful initial investigation for idiopathic unilateral vocal fold palsy, particularly in cases with vocal fold paralysis.


Assuntos
Tomografia Computadorizada por Raios X/estatística & dados numéricos , Paralisia das Pregas Vocais/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Singapura , Prega Vocal/diagnóstico por imagem
9.
Mol Genet Metab Rep ; 24: 100627, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32760653

RESUMO

Pathogenic variants in RANBP2 cause autosomal dominant familial and recurrent Acute Necrotizing Encephalopathy of Childhood (ANEC). Affected children typically experience a 3-stage disease: a 3 to 5 days prodrome of non-specific febrile illness, acute encephalopathy, and recovery with or without neurological sequelae or death. Neuroradiological finding of bilateral symmetrical thalamic lesions raise the suspicion of this diagnosis. A devastating disease, reported mortality approaches 1/3 of those affected and only approximately 10% of patients recover completely without sequelae. We report a Malaysian family with RANBP2 pathogenic variant c.1754C>T (p.Thr585Met). The clinical presentation and course over a maximum of 7 years, as well as neuroradiological features of the 3 affected children are described. In contrast to the reported high mortality and morbidity, our patients have recovered with minor sequelae. We would like to highlight the absence of pathogenic variants in both parents' blood, raising the possibility of germline mosaicism in one of the parents as the underlying genetic mechanism of inheritance. To our knowledge, this is the first report of germline mosaicism in RANBP2 Susceptibility to Infection-induced Encephalopathy.

10.
Pituitary ; 23(3): 258-265, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32189207

RESUMO

PURPOSE: Highlight and characterize manifestations, diagnostic/management approaches and outcomes in a contemporary cohort of patients with pituitary metastases (PM) from a large European pituitary center-over 10 years. METHODS: Retrospective review of PM cases between 1/2009 and 12/2018. Clinical, laboratory, imaging data at PM detection and during follow-up were analysed. RESULTS: 18 cases were identified (14 females; median age at diagnosis 61.5 years). Most common primary malignancies were lung (39%) and breast (32%). Most frequent presenting manifestation was visual dysfunction (50%). Gonadotrophin, ACTH, TSH deficiency were diagnosed in 85%, 67%, 46% of cases, respectively; diabetes insipidus (DI) was present in 17%. 33% of cases were detected during investigation for symptoms unrelated to PM. PM management included radiotherapy (44%), transsphenoidal surgery (17%), transsphenoidal surgery and radiotherapy (6%) or monitoring only (33%). One-year survival was 49% with median survival from PM detection 11 months (range 2-47). CONCLUSIONS: In our contemporary series, clinical presentation of PM has evolved; we found increased prevalence of anterior hypopituitarism, decreased rates of DI and longer survival compared with older literature. Increased availability of diagnostic imaging, improvements in screening and recognition of pituitary disease and longer survival of patients with metastatic cancer may be contributing factors.


Assuntos
Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Adulto , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/etiologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/etiologia , Estudos Retrospectivos
11.
J Dent ; 71: 31-37, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29378225

RESUMO

OBJECTIVE: The main objective of this study was to evaluate the accuracy of optical coherence tomography (OCT) in detecting naturally occurring non-cavitated fissure caries (NCFC) in totality and at different loci by visually assessing cross-sectional OCT scans (B-scan) with an interpretation criterion. The secondary objective was to evaluate the agreement between dimensions of NCFC measured with OCT and polarized light microscopy (PLM). METHODS: 71 investigation sites of sound fissure and naturally occurring NCFC on human extracted premolars were identified and scanned with a swept-source OCT. The teeth were then sectioned bucco-lingually at the investigation sites and imaged using PLM. Two calibrated examiners trained on the B-scan NCFC visual interpretation criteria established for this study, assessed the investigation sites and results were validated against PLM. RESULTS: Detection sensitivity of B-scan for NCFC when fissures were assessed in totality, or on the slopes or walls separately are 0.98, 0.95, 0.94 and specificity are 0.95, 0.90, and 0.95. One-way ANOVA showed that width measurements of wall loci done with OCT and PLM were not statistically different. However, OCT height measurements of slope loci were statistically bigger with a constant bias of 0.08 mm (of which is not clinically significant) and OCT height measurements of wall loci were statistically smaller (0.57 mm) and Bland-Altman plots indicated presence of proportionate bias. CONCLUSION: Visual assessment of B-scans with the interpretation criteria resulted in both high specificity and sensitivity and were not affected by loci location. OCT width measurement of wall loci is in agreement with PLM. CLINICAL SIGNIFICANCE: Unanimous high sensitivity in this and previous studies indicate that visual assessment of B-scans reliably rule out NCFC. Detection accuracy was not affected by loci location. Width of wall loci and/or height of slope loci in OCT B-scan are to be used for monitoring NCFC but not height of wall loci.


Assuntos
Cárie Dentária/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Anatomia Transversal , Dente Pré-Molar , Cárie Dentária/patologia , Sensibilidade da Dentina , Humanos , Microscopia de Polarização/métodos , Selantes de Fossas e Fissuras , Sensibilidade e Especificidade
12.
Int Wound J ; 15(2): 225-236, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29243356

RESUMO

The aim of this study was to identify current research on turning frequencies of adult bed-bound patients and inform future turning practices for hospitals based on evidence-based practice. We undertook a scoping review framework that provided a transparent and systematic methodology using 8 electronic databases (CINAHL, PubMed, Cochrane Library, ScienceDirect, PsycINFO, Scopus, ProQuest, and Web of Science) to identify articles published from 2000 to 2016. Articles were included if they focused on the prevention of hospital-acquired pressure ulcers related to the frequency of turning or repositioning of bed-bound patients. Literature search and data extraction were performed independently by 3 authors. The study followed the PRISMA guidelines. In total, 911 articles were identified, of which 10 were eligible. Of the eligible articles, 8 studies could not reach a conclusion on the effective frequency of turning and duration for repositioning patients to prevent the development of pressure ulcers. Only 2 studies found significant differences among the intervention and control groups. Results regarding turning and repositioning schedules are inconclusive; however, the topic needs further exploration to improve the outdated guidelines surrounding pressure ulcer prevention. This may, in turn, make the work of nurses more efficient and make treatment cost-effective for both the patients and the hospitals.


Assuntos
Movimentação e Reposicionamento de Pacientes/métodos , Movimentação e Reposicionamento de Pacientes/normas , Posicionamento do Paciente/métodos , Posicionamento do Paciente/normas , Úlcera por Pressão/prevenção & controle , Higiene da Pele/métodos , Higiene da Pele/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Pessoas Acamadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto
13.
AJNR Am J Neuroradiol ; 38(1): 127-131, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27932510

RESUMO

BACKGROUND AND PURPOSE: The introduction of liquid embolic agents has revolutionized endovascular approach to cranial vascular malformations. The aim of the study was to retrospectively assess the efficacy and safety of Precipitating Hydrophobic Injectable Liquid (PHIL), a new nonadhesive liquid embolic agent, in the treatment of patients with cranial dural arteriovenous fistulas. The primary end point was the rate of complete occlusion of dural arteriovenous fistulas. Secondary end points included the incidence of adverse events and clinical status at 3-month follow-up. MATERIALS AND METHODS: This was a retrospective multicenter study. Twenty-six consecutive patients with dural arteriovenous fistulas (de novo or previously treated) treated by injection of PHIL only or with PHIL in combination with other embolization products (such as Onyx or detachable coils) were included in the study. Recruitment started in August 2014 and ended in September 2015. RESULTS: Twenty-two (85%) patients were treated with PHIL only, with 3 patients treated with both PHIL and Onyx, and 1, with both PHIL and coils. Immediate complete angiographic occlusion was achieved in 20 (77%) patients. Of the 6 patients with residual fistulas, 3 were retreated with PHIL and 1 achieved angiographic cure. An adverse event was seen in 1 patient who developed worsening of preexisting ataxia due to acute thrombosis of the draining vein. CONCLUSIONS: PHIL appears to be safe and effective for endovascular treatment of cranial dural arteriovenous fistulas. Short-term angiographic and clinical results are comparable with those of Onyx, with the added advantage of easier preparation and improved homogeneous cast visualization. The use of iodine as a radio-opacifier also produces considerably less artifacts on CT compared with tantalum-based embolic materials.


Assuntos
Embolização Terapêutica/métodos , Malformações Arteriovenosas Intracranianas/terapia , Adulto , Idoso , Dimetil Sulfóxido/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polivinil/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
14.
Caries Res ; 48(3): 254-62, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24481141

RESUMO

BACKGROUND: Measurement of initial enamel erosion is currently limited to in vitro methods. Optical coherence tomography (OCT) and quantitative light-induced fluorescence (QLF) have been used clinically to study advanced erosion. Little is known about their potential on initial enamel erosion. OBJECTIVES: To evaluate the sensitivity of QLF and OCT in detecting initial dental erosion in vitro. METHODS: 12 human incisors were embedded in resin except for a window on the buccal surface. Bonding agent was applied to half of the window, creating an exposed and non-exposed area. Baseline measurements were taken with QLF, OCT and surface microhardness. Samples were immersed in orange juice for 60 min and measurements taken stepwise every 10 min. QLF was used to compare the loss of fluorescence between the two areas. The OCT system, OCS1300SS (Thorlabs Ltd.), was used to record the intensity of backscattered light of both areas. Multiple linear regression and paired t test were used to compare the change of the outcome measures. RESULTS: All 3 instruments demonstrated significant dose responses with the erosive challenge interval (p < 0.05) and a detection threshold of 10 min from baseline. Thereafter, surface microhardness demonstrated significant changes after every 10 min of erosion, QLF at 4 erosive intervals (20, 40, 50 and 60 min) while OCT at only 2 (50 and 60 min). CONCLUSION: It can be concluded that OCT and QLF were able to detect demineralization after 10 min of erosive challenge and could be used to monitor the progression of demineralization of initial enamel erosion in vitro.


Assuntos
Esmalte Dentário/patologia , Tomografia de Coerência Óptica/métodos , Erosão Dentária/diagnóstico , Bebidas/efeitos adversos , Citrus sinensis , Progressão da Doença , Fluorescência , Dureza , Humanos , Concentração de Íons de Hidrogênio , Processamento de Imagem Assistida por Computador/métodos , Técnicas In Vitro , Luz , Espalhamento de Radiação , Fatores de Tempo , Desmineralização do Dente/diagnóstico , Desmineralização do Dente/patologia , Erosão Dentária/patologia
15.
Respir Med ; 107(11): 1810-3, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24070567

RESUMO

INTRODUCTION: Adenovirus causing severe fatal pneumonia has been well described in infants, children, and patients with immunocompromised function, but reports in previously healthy adults are rare. We report 3 cases of severe adenovirus pneumonia in whom conventional mechanical ventilation failed and required extracorporeal membrane oxygenation support. METHODS: Retrospective case records review of 3 patients admitted to the medical intensive care unit, Singapore General Hospital, a tertiary care university-affiliated hospital, with severe adenovirus pneumonia requiring extracorporeal membrane oxygenation support from February to March 2013. RESULTS: All 3 patients were previously healthy immunocompetent adults from the community with negative HIV serology. Duration prior to development of respiratory failure requiring intubation and invasive mechanical ventilation was 2, 8 and 3 days. Veno-venous extracorporeal membrane oxygenation (ECMO) support as rescue ventilation was instituted in all 3 patients after 2, 16, and 5 days of conventional mechanical ventilator support. Duration on ECMO support was 16, 22, and 9 days and mechanical ventilation was 18, 62, and 19 days respectively. Length of stay in intensive care unit was 18, 68, and 21 days, and length of stay in hospital was 20, 70, and 31 days respectively. Two of the 3 patients died. CONCLUSION: The mainstay of treatment for patients with severe adenovirus pneumonia is still supportive, with the use of antivirals not apparently effective. Whilst ECMO support for rescue ventilation may be considered, the outcomes do not appear as promising as other viral pneumonias, mirroring that previously described in the paediatric population.


Assuntos
Adenoviridae/classificação , Infecções por Adenovirus Humanos/terapia , Oxigenação por Membrana Extracorpórea , Pneumonia Viral/terapia , Adenoviridae/isolamento & purificação , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/virologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Pressão Parcial , Pneumonia Viral/sangue , Pneumonia Viral/virologia , Estudos Retrospectivos , Sorotipagem
16.
Ann Oncol ; 23(4): 1023-9, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21778300

RESUMO

BACKGROUND: Chemotherapy in combination with small-molecule epidermal growth factor receptor inhibitors has yielded inconsistent results. Based on preclinical models, we conducted a phase I trial of two schedules of lapatinib and vinorelbine. PATIENT AND METHODS: Patients had advanced solid tumors and up to two prior chemotherapeutic regimens. Patients were enrolled on two dose-escalating schedules of lapatinib, continuous (arm A) or intermittent (arm B), with vinorelbine on days 1, 8, and 15 of a 28-day cycle. Tumors from a subset of patients were evaluated for gene mutations and expression of targets of interest. RESULTS: Fifty-one patients were treated. The most common grade 3/4 toxic effects included leukopenia, neutropenia, and fatigue. Dose-limiting toxic effects were grade 3 infection, febrile neutropenia, and diarrhea (arm A) and bone pain and fatigue (arm B). The maximum tolerated dose was vinorelbine 20 mg/m(2) weekly and lapatinib 1500 mg daily (arm A) and vinorelbine 25 mg/m(2) weekly and lapatinib 1500 mg intermittently (arm B). One patient on each arm had a complete response; both had human epidermal growth factor receptor 2-positive breast cancer. In a subset of patients, lack of tumor PTEN expression correlated with a shorter time to progression. CONCLUSION: In an unselected population, two schedules of lapatinib and vinorelbine were feasible and well tolerated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Estimativa de Kaplan-Meier , Lapatinib , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Quinazolinas/administração & dosagem , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina
17.
Curr Med Chem ; 18(31): 4836-50, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21919844

RESUMO

Clinical studies and case reports have identified a number of herb-drug interactions potentiated by the concurrent use of herbal medicines with prescription drugs. The purpose of this paper is to discuss the mechanisms and clinical implications of such herb-drug interactions by reviewing published human studies. Both pharmacokinetic and pharmacodynamic components may be involved in herbdrug interactions, although metabolic induction or inhibition is a common underlying mechanism for many herb-drug interactions. Drugs that have a high potential to interact with herbal medicines usually have a narrow therapeutic index, including warfarin, digoxin, cyclosporine, tacrolimus, amitriptyline, midazolam, indinavir, and irinotecan. Many of them are substrates of cytochrome P450s (CYPs) and/or P-glycoprotein (P-gp). Herbal medicines that are reported to interact with drugs include garlic (Allium sativum), ginger (Zingiber officinale), ginkgo (Ginkgo biloba), ginseng (Panax ginseng), and St. John's wort (Hypericum perforatum). For example, garlic has been shown to increase the clotting time and international normalized ratio (INR) of warfarin, cause hypoglycaemia when taken with chlorpropamide, and reduce the area under the plasma concentration-time curve (AUC) and maximum concentration of saquinavir in humans. Similarly, case reports have demonstrated that ginkgo may potentiate bleeding when combined with warfarin or aspirin, increases blood pressure when combined with thiazide diuretics, and has even led to a coma when combined with trazodone, a serotonin antagonist and reuptake inhibitor used to treat depression. Furthermore, ginseng reduced the blood levels of warfarin and alcohol as well as induced mania if taken concomitantly with phenelzine, a non-selective and irreversible monoamine oxidase inhibitor used as an antidepressant and anxiolytic agent. Lastly, multiple herb-drug interactions have been identified with St. John's wort that involve significantly reduced AUC and blood concentrations of warfarin, digoxin, indinavir, theophylline, cyclosporine, tacrolimus, amitriptyline, midazolam, and phenprocoumon. The clinical consequence of herb-drug interactions varies, from being well-tolerated to moderate or serious adverse reactions, or possibly life-threatening events. Undoubtedly, the early and timely identification of herb-drug interactions is imperative to prevent potentially dangerous clinical outcomes. Further well-designed studies are warranted to address the mechanisms and clinical significance of important herb-drug interactions.


Assuntos
Interações Ervas-Drogas , Preparações Farmacêuticas/metabolismo , Preparações de Plantas/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Alho/química , Ginkgo biloba/química , Humanos , Panax/química , Preparações Farmacêuticas/química , Preparações de Plantas/química , Preparações de Plantas/farmacocinética
18.
Caries Res ; 45 Suppl 1: 60-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21625134

RESUMO

We define erosion as a partial demineralisation of enamel or dentine by intrinsic or extrinsic acids and erosive tooth wear as the accelerated loss of dental hard tissue through the combined effect of erosion and mechanical wear (abrasion and attrition) on the tooth surface. Most experts believe that during the last decade there has been a significant increase in the prevalence and severity of erosive tooth wear, particularly in adolescents. Even when erosive wear occurs in its milder forms, this is a matter of concern, as it may compromise the integrity of an otherwise healthy dentition in later life. The erosive wear process is complicated and modified by many chemical, behavioural and associated processes in the mouth. If interventions are to be developed it is therefore important that in vivo methods are developed to assess the outcomes of the erosion and erosive wear processes and the effects of interventions upon them. This paper discusses potential methods of investigating erosion and erosive wear in vivo and the difficulties associated with clinical studies.


Assuntos
Erosão Dentária/fisiopatologia , Ensaios Clínicos como Assunto , Esmalte Dentário/patologia , Dentina/patologia , Humanos , Projetos de Pesquisa , Sujeitos da Pesquisa , Abrasão Dentária/fisiopatologia , Atrito Dentário/fisiopatologia , Desmineralização do Dente/diagnóstico , Desmineralização do Dente/fisiopatologia , Erosão Dentária/diagnóstico
19.
Trop Biomed ; 28(1): 48-54, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21602768

RESUMO

Ovitrap surveillance was conducted in methodically selected areas in Bentong, Pahang, Malaysia from June 2008 till December 2009 in order to identify insular sites with stable Aedes aegypti population. Eleven sites were surveyed in Bentong district, Pahang, and one of these locations (N3º33' E101º54') was found to have an ovitrap index of Ae. aegypti and Aedes albopictus ranging from 8%-47% and 37%-78% respectively, indicating that this site could be a high-risk area for dengue outbreak. Ae. aegypti larvae were found in both indoor and outdoor ovitraps (p>0.05) while significant difference between the populations of Ae. albopictus larvae from indoors and outdoors was observed (p<0.01). Data collected in this study could provide important entomological information for designing an effective integrated vector control programme to combat Aedes mosquitoes in this area.


Assuntos
Aedes/crescimento & desenvolvimento , Vetores de Doenças , Animais , Dengue/epidemiologia , Dengue/transmissão , Ecossistema , Humanos , Malásia , Densidade Demográfica
20.
BMJ Case Rep ; 20112011 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22715259

RESUMO

A rare syndrome of rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) has been recently described. We report the first patient with this syndrome in Southeast Asia and review reported cases to date. Our patient was good health with normal development until the age of 2. He then developed hyperphagic obesity, hypersomnolence, seizures, alveolar hypoventilation, central hypothyroidism, sodium and water dysregulation, gastrointestinal dysmotility, strabismus, disordered temperature and irregular heart rate, altered sweating, delayed puberty, mental retardation and recurrent respiratory tract infections. The cardiomyopathy with heart failure and abnormal cerebral spinal fluid (CSF) neurotransmitter analysis present in our patient have not been reported previously. Tumours of the sympathetic nervous system are known to be associated with this syndrome but had not been found in our patient at the time of reporting. We highlight the difficulty of achieving the diagnosis of ROHHAD syndrome and its overlap with other well-established disease entities. The mortality and morbidity resulting from the high incidence of cardiorespiratory arrest may be prevented by early ventilatory support.


Assuntos
Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças Hipotalâmicas/diagnóstico , Hipoventilação/diagnóstico , Obesidade/diagnóstico , Criança , Humanos , Masculino , Síndrome
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