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1.
Heliyon ; 10(2): e24343, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38298671

RESUMO

This work deals with the synthesis, structural characterization and applications of N-halamine glycinate functionalized silica-mesoporous silica coated ZnO-NPs/AC composite for water disinfection. Several nanocomposite materials were obtained: ZnO-NPs/AC, ZnO-NPs/AC@SiO2, ZnO-NPs/AC@SiO2@mSiO2, ZnO-NPs@SiO2@mSiO2-Gly and ZnO-NPs@SiO2@mSiO2-N-halamine-Gly. These nanocomposite materials were fully characterized via different physiochemical techniques including: FTIR, TGA, XPS, XRD, SEM, TEM and BET. XRD indicated a predominance of crystalline pattern of ZnO-NPs impregnated into activated carbon (AC) and their silica and m-mesoporous silica coating precursors. The FTIR spectra confirmed an immense combination between ZnO-NPs and AC of ZnO-NPs/AC nanocomposite as well as its interactions with coated silica precursors. SEM, TEM images illustrated that the fabricated ZnO-NPs/AC nanocomposites are well coated with silica-mesoporous silica functionalized N-halamine. The distinctive surface area has decreased from 800 m2/g for pristine AC to 772 m2/g for ZnO-NPs/AC and to 282 m2/g for ZnO-NPs/AC@SiO2 and to 139 m2/g for ZnO-NPs/AC@SiO2@mSiO2 and to 15.4 m2/g for ZnO-NPs@SiO2@mSiO2-N-Gly. All those nanocomposites showed good efficacy against all four bacterial species, with higher inhibition zones for the 2 g-positive bacteria than that of the 2 g-negative ones. The ZnO@SiO2@mSiO2-N-halamine-Gly exhibited the high zone inhibition against all tested bacteria except for E. Coli.

2.
Malays Orthop J ; 17(3): 84-87, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38107360

RESUMO

Tibial tuberosity avulsion fracture is a rare injury, and bilateral occurrence is more uncommon. Periosteal sleeve fracture is a unique fracture pattern which was first described in the lower pole of patella in children. We are reporting a rare case of bilateral tibial tuberosity sleeve fracture in a teenage boy which occurred while sprinting. The patient underwent open reduction, pull through suture fixation of the bilateral tibial tuberosity and screw fixation of left tibial tuberosity. Post-operative rehabilitation included gradual increment of range of motion with hinged brace and quadriceps muscle strengthening. Close follow-up was done to monitor the progression of his recovery. At six months follow-up, the patient recovered well. Both knees had full range of motion with an intact extensor mechanism.

3.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1006349

RESUMO

@#Tibial tuberosity avulsion fracture is a rare injury, and bilateral occurrence is more uncommon. Periosteal sleeve fracture is a unique fracture pattern which was first described in the lower pole of patella in children. We are reporting a rare case of bilateral tibial tuberosity sleeve fracture in a teenage boy which occurred while sprinting. The patient underwent open reduction, pull through suture fixation of the bilateral tibial tuberosity and screw fixation of left tibial tuberosity. Post-operative rehabilitation included gradual increment of range of motion with hinged brace and quadriceps muscle strengthening. Close follow-up was done to monitor the progression of his recovery. At six months follow-up, the patient recovered well. Both knees had full range of motion with an intact extensor mechanism.

4.
Malays Orthop J ; 16(2): 136-139, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35992986

RESUMO

Macrodystrophia Lipomatosa (MDL) of the toe is a rare, congenital, disproportionate overgrowth involving one or more digits in the lower limb. Despite being a benign condition, when left untreated, it may cause physical impairment and interfere with daily activities. This form of localised gigantism is the result of excessive proliferation of fibroadipose tissue within the nerve along with associated macrodactyly. The mainstay of treatment is debulking or amputation to accommodate the patient's daily activities, as well as for cosmesis. In this case report, the clinical and radiographic findings, anatomical descriptions, and histopathological findings are presented. The difference between MDL, fibrolipomatous hamartoma (FLH) and lipomatosis of the nerve (LON) are also discussed.

5.
6.
Malays Orthop J ; 15(2): 26-35, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34429819

RESUMO

INTRODUCTION: The guided growth technique is an alternative to corrective osteotomy for treating angular deformities of the extremities. It has the advantage of being minimally invasive and is effective in a growing child. This study reports on the outcome of guided growth technique using a plate in correcting knee angular deformities. MATERIAL AND METHODS: We conducted a retrospective study of children with angular deformity of the knee treated by the guided growth technique from January 2010 to December 2015 in a tertiary centre. The guided growth technique was done using either the flexible titanium plate (8-plate) or the 2-hole reconstruction plate. Correction of deformity was assessed on radiographs by evaluating the mechanical axis deviation and tibiofemoral angle. The implants were removed once deformity correction was achieved. RESULTS: A total of 17 patients (27 knees) were evaluated. Twenty-two knees (81.5%) achieved complete correction of the deformity. The median age was 4.0 (interquartile range 3.0-6.0) years and the median Body Mass Index (BMI) was 26.0 (25.0-28.0). There were 7 unilateral and 10 bilateral deformities with different pathologies (14 tibia vara, 3 genu valgus). The median rate of correction was 0.71° per month. One patient (1 knee) had screw pull-out and two patients (4 knees) had broken screws in the proximal tibia. Three patients (5 knees) failed to achieve complete correction and were subsequently treated with corrective osteotomies. Out of five patients (8 knees) who were followed-up for at least 12 months after removal of hardware, two had rebound deformities. No permanent growth retardation occurred in our patients. CONCLUSION: Our outcome for guided growth to correct knee angular deformity was similar to other studies. Guided growth is safe to perform in children below 12 years old and has good outcome in idiopathic genu valgus and Langeskiold II for tibia vara. Patients should be observed for recurrence until skeletal maturity following implant removal.

7.
Malays Orthop J ; 15(2): 122-128, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34429832

RESUMO

INTRODUCTION: To compare the anxiety levels demonstrated by children during cast removal procedure between oscillating saw vs cast shear methods. MATERIAL AND METHODS: A randomised prospective study of 102 children (mean age 8.3 ± 3.5 years) with fractures involving upper or lower limbs. Children undergoing removal of cast were divided into 2 groups; either by an oscillating saw or a cast cutting shear. The level of anxiety was assessed by recording the heart rate with a portable fingertip pulse oximeter before, during and after removal of the cast. Objective assessment was performed by documenting the fear level on Children's Fear Scale (CFS). RESULTS: There was a significant increase in the heart rate of children during cast removal while using the oscillating saw compared to cast shear (p<0.05). The noise level produced by the saw exceeded 80 dB (mean 103.3 dB). The fear level was significantly lower in the cast shear group (p<0.05). CONCLUSION: The noise produced by the oscillating saw was associated with an increased anxiety level in children undergoing cast removal. Cast shear is a simple and inexpensive instrument that can be used for cast removal in overly anxious children.

8.
Malays Orthop J ; 15(1): 132-134, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33880161

RESUMO

Femoral neck stress fractures are rare in children. To the best of our knowledge, the tension type stress fracture has been reported only twice in the English language literature. We report on a five years follow-up of a 10-year-old boy with this injury which was initially missed. The fracture healed after screw fixation. We highlight the importance of considering stress fracture as a differential diagnosis in a child with chronic hip pain. A careful physical examination and the appropriate imaging will avoid missing the diagnosis.

9.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-920838

RESUMO

@#Introduction: The guided growth technique is an alternative to corrective osteotomy for treating angular deformities of the extremities. It has the advantage of being minimally invasive and is effective in a growing child. This study reports on the outcome of guided growth technique using a plate in correcting knee angular deformities. Materials and methods: We conducted a retrospective study of children with angular deformity of the knee treated by the guided growth technique from January 2010 to December 2015 in a tertiary centre. The guided growth technique was done using either the flexible titanium plate (8-plate) or the 2- hole reconstruction plate. Correction of deformity was assessed on radiographs by evaluating the mechanical axis deviation and tibiofemoral angle. The implants were removed once deformity correction was achieved. Results: A total of 17 patients (27 knees) were evaluated. Twenty-two knees (81.5%) achieved complete correction of the deformity. The median age was 4.0 (interquartile range 3.0-6.0) years and the median Body Mass Index (BMI) was 26.0 (25.0-28.0). There were 7 unilateral and 10 bilateral deformities with different pathologies (14 tibia vara, 3 genu valgus). The median rate of correction was 0.71° per month. One patient (1 knee) had screw pull-out and two patients (4 knees) had broken screws in the proximal tibia. Three patients (5 knees) failed to achieve complete correction and were subsequently treated with corrective osteotomies. Out of five patients (8 knees) who were followed-up for at least 12 months after removal of hardware, two had rebound deformities. No permanent growth retardation occurred in our patients. Conclusion: Our outcome for guided growth to correct knee angular deformity was similar to other studies. Guided growth is safe to perform in children below 12 years old and has good outcome in idiopathic genu valgus and Langeskiold II for tibia vara. Patients should be observed for recurrence until skeletal maturity following implant removal.

10.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-920809

RESUMO

@#Femoral neck stress fractures are rare in children. To the best of our knowledge, the tension type stress fracture has been reported only twice in the English language literature. We report on a five years follow-up of a 10-year-old boy with this injury which was initially missed. The fracture healed after screw fixation. We highlight the importance of considering stress fracture as a differential diagnosis in a child with chronic hip pain. A careful physical examination and the appropriate imaging will avoid missing the diagnosis.

11.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-922745

RESUMO

@#Introduction: To compare the anxiety levels demonstrated by children during cast removal procedure between oscillating saw vs cast shear methods. Material and methods: A randomised prospective study of 102 children (mean age 8.3 ± 3.5 years) with fractures involving upper or lower limbs. Children undergoing removal of cast were divided into 2 groups; either by an oscillating saw or a cast cutting shear. The level of anxiety was assessed by recording the heart rate with a portable fingertip pulse oximeter before, during and after removal of the cast. Objective assessment was performed by documenting the fear level on Children’s Fear Scale (CFS). Results: There was a significant increase in the heart rate of children during cast removal while using the oscillating saw compared to cast shear (p<0.05). The noise level produced by the saw exceeded 80 dB (mean 103.3 dB). The fear level was significantly lower in the cast shear group (p<0.05). Conclusion: The noise produced by the oscillating saw was associated with an increased anxiety level in children undergoing cast removal. Cast shear is a simple and inexpensive instrument that can be used for cast removal in overly anxious children.

12.
J Child Orthop ; 13(1): 82-88, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30838080

RESUMO

PURPOSE: Perthes' disease (PD) results from loss of blood supply to the hip and can progress to femoral head deformity. MRI in the early course of the disease can provide data on the initial extent of infarct. Vascularity of the femoral head is assessed by gadolinium-enhanced MRI (contrast MRI), which may be improved by the digital subtraction technique (subtraction MRI). We hypothesized that gadolinium-enhanced MRI without subtraction was comparable with subtraction MRI in depicting the femoral head perfusion. METHODS: In all, 34 patients (34 hips) with unilateral PD had gadolinium-enhanced MRI as part of a prospectively randomized study. Nine patients had three MRIs, 15 had two and ten had a single MRI. Measurement of perfusion of the femoral head (MRI perfusion index) was obtained using digital image analysis on all the MRIs, including both before and after subtraction. A paired sample t-test was performed to compare the measurements. RESULTS: The mean age of the patients was 8.9 years (sd 1.6). At the time of diagnosis, the subtraction MRI did not elicit a statistically significant difference in MRI perfusion index measurements when compared with the contrast MRI (p = 0.19). The same findings were found when including all patients at various stages of the disease (p = 0.30). Qualitatively, although some subtraction MRI images showed superior delineation of epiphysis, there are no significant differences throughout the whole series. CONCLUSION: Although the current literature supports the increasing role of the subtraction MRI for PD management, our study proposed that the contrast MRI without subtraction technique appears adequate in assessing femoral head perfusion. LEVEL OF EVIDENCE: Level I - Diagnostic study.

13.
Aliment Pharmacol Ther ; 45(11): 1390-1402, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28370090

RESUMO

BACKGROUND: The goal of hepatorenal syndrome type 1 (HRS-1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS-1, where it is available. AIM: To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS-1. METHODS: Pooled patient-level data from two large phase 3, randomised, placebo-controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 µmol/L], 90-day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1-2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days. RESULTS: The pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27% vs. 14%; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between-group difference in SCr concentration of -53.0 µmol/L (P < 0.0001). Lower SCr, lower mean arterial pressure and lower total bilirubin and absence of known precipitating factors for HRS were independent predictors of HRS reversal and longer survival in terlipressin-treated patients. CONCLUSIONS: Terlipressin plus albumin resulted in a significantly higher rate of HRS reversal vs. albumin alone in patients with HRS-1. Terlipressin treatment is associated with improved renal function. (ClinicalTrials.gov identifier: OT-0401, NCT00089570; REVERSE, NCT01143246).


Assuntos
Albuminas/uso terapêutico , Síndrome Hepatorrenal/tratamento farmacológico , Lipressina/análogos & derivados , Vasoconstritores/uso terapêutico , Adulto , Ensaios Clínicos Fase III como Assunto , Quimioterapia Combinada , Feminino , Humanos , Lipressina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Terlipressina , Resultado do Tratamento
14.
Gut ; 66(2): 352-361, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-26887815

RESUMO

OBJECTIVE: Natural killer (NK) cells are important mediators of liver inflammation in chronic liver disease. The aim of this study was to investigate why liver transplants (LTs) are not rejected by NK cells in the absence of human leukocyte antigen (HLA) matching, and to identify a tolerogenic NK cell phenotype. DESIGN: Phenotypic and functional analyses on NK cells from 54 LT recipients were performed, and comparisons made with healthy controls. Further investigation was performed using gene expression analysis and donor:recipient HLA typing. RESULTS: NK cells from non-HCV LT recipients were hypofunctional, with reduced expression of NKp46 (p<0.05) and NKp30 (p<0.001), reduced cytotoxicity (p<0.001) and interferon (IFN)-γ secretion (p<0.025). There was no segregation of this effect with HLA-C, and these functional changes were not observed in individuals with HCV. Microarray and RT-qPCR analysis demonstrated downregulation of STAT4 in NK cells from LT recipients (p<0.0001). Changes in the expression levels of the transcription factors Helios (p=0.06) and Hobit (p=0.07), which control NKp46 and IFNγ expression, respectively, were also detected. Hypofunctionality of NK cells was associated with impaired STAT4 phosphorylation and downregulation of the STAT4 target microRNA-155. Conversely in HCV-LT NK cell tolerance was reversed, consistent with the more aggressive outcome of LT for HCV. CONCLUSIONS: LT is associated with transcriptional and functional changes in NK cells, resulting in reduced activation. NK cell tolerance occurs upstream of major histocompatibility complex (MHC) class I mediated education, and is associated with deficient STAT4 phosphorylation. STAT4 therefore represents a potential therapeutic target to induce NK cell tolerance in liver disease.


Assuntos
Tolerância Imunológica/genética , Células Matadoras Naturais/imunologia , Transplante de Fígado , Ativação Linfocitária/genética , Fator de Transcrição STAT4/genética , Fator de Transcrição STAT4/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Regulação para Baixo , Feminino , Antígenos HLA-C/imunologia , Hepatite C Crônica/complicações , Hepatite C Crônica/imunologia , Teste de Histocompatibilidade , Humanos , Fator de Transcrição Ikaros/genética , Células Matadoras Naturais/química , Células Matadoras Naturais/metabolismo , Ativação Linfocitária/imunologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Receptor 1 Desencadeador da Citotoxicidade Natural/análise , Receptor 3 Desencadeador da Citotoxicidade Natural/análise , Fenótipo , Fosforilação , Fator de Transcrição STAT4/metabolismo
15.
Neoplasma ; 62(1): 72-80, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25563369

RESUMO

UNLABELLED: The Phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA) is an important regulator of cell signaling pathways in human cancers. Mutations in PIK3CA were found to be associated with more aggressive clinical outcome and aberrant activation of cellular mechanisms in cancers. Hence the present study aimed to understand the mutations in the PIK3CA gene in head and neck squamous cell carcinomas (HNSCC). After the approval of the Institutional Ethics Committee we recruited 129 HNSCC patients and 150 healthy controls for screening of mutations in the helical (exon9) and kinase domain (exon 20) of the PIK3CA gene using PCR, SSCP and Sanger Sequencing. We found about 60.46% of HNSCC patients and 26% of controls with the following mutations 1634A>C (E545A) and 3075C>T (T1025T) in the helical and kinase domains of PIK3CA. Both these mutations 1634A>C and 3075C>T were more prominent in oral cancers, advanced stages of HNSCC and tobacco plus alcohol habits (p<0.05). Hence, we conclude that the distribution of mutations of PIK3CA in HNSCC were associated with demographic (tobacco and alcohol) and clinical parameters (advanced stage, primary site) of HNSCC. It is possible that when this pathway is overactive due to mutations, it may reduce apoptosis and allow proliferation of the tumor cells. Therefore we propose that these mutations may serve as prognostic biomarkers, and can also be proposed as novel therapeutic targets for HNSCC. KEYWORDS: PI3 kinase, gene polymorphism, helical domain, kinase domain, oral cancers.

16.
Indian J Cancer ; 52(1): 127-32, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26838000

RESUMO

BACKGROUND: The three direct factors that could lead cancer patients to anemia, apart from therapy are iron deficiency, inflammatory cytokines surge and decreased erythropoietin (Epo). Our aim was to quantify biochemical and hematologic markers serum Epo, ferritin (Fe) and tumor necrosis factor-alpha (TNF-α) along with hemoglobin (Hb) to understand the associations between these factors, patient characteristics and anemia. MATERIALS AND METHODS: The study group consisted of 100 anemic cancer patients and 80 controls. Biochemical marker levels were determined by the enzyme linked immunosorbent assay on an autoanalyser. Univarient analysis, t-test, ANOVA, Bonferroni test, linear regression was performed to find correlations and associations among various factors. RESULTS: The baseline serum Epo (153.07 ± 173.88 vs. 23.607 ± 36.462) and Fe levels (233.53 ± 257.12 vs. 23.06 ± 20.04) were adequately high in cases compared with that controls (P ≤ 0.001). Considerable raise in TNF-α levels was also observed (16.26 ± 13.44 vs. 11.2375 ± 4.84) (P = 0.001). TNF-α correlated positively (P = 0.022) with Epo and Fe (P = 0.000), which was also evident from large effect size of Epo (r2 = 0.414), TNF-α (r2 = 0.369), Hb (r2 = 0.226). Epo and Hb were negatively correlated (ß = -0.375, P = 0.001) and Epo production was found to be appropriate for the degree of anemia (O/P ratio of 3.51 ± 1.26 vs. 1.43 ± 0.47). A strong association was seen between Hb, Epo and TNF-α in hematological and gynecological malignancies for different grades of anemia. Men were more prone to life-threatening anemia (13%) than women (9%). CONCLUSION: Anemia in cancers was not because of inadequate Epo or Fe levels, but because of improper Epo response. Further studies on molecular analysis of Epo, biochemical and molecular interplay between Epo and TNF-α could explain a rationale for anemia in cancers.


Assuntos
Anemia/sangue , Eritropoetina/sangue , Ferro/sangue , Neoplasias/sangue , Adulto , Anemia/complicações , Anemia/patologia , Feminino , Hemoglobinas/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/patologia , Fator de Necrose Tumoral alfa/sangue
17.
Clin Med (Lond) ; 13(1): 37-41, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23472493

RESUMO

AIMS: To assess the utility of flexible sigmoidoscopy (FS) and minimal preparation CT (MPCT) in investigating lower gastrointestinal (LGI) symptoms in elderly patients who are too frail to undergo colonoscopy or spiral CT. METHODS: All FS examinations performed in patients aged over 70 between 1 January and 31 December 2008 were analysed. Predictors of usefulness were determined using multivariable analysis. In patients who also underwent MPCT, we analyzed the correlation between FS and MPCT. RESULTS: 426 FS were performed. Bowel preparation was inadequate in 24% of procedures. Indications in which FS was useful were: radiological abnormality (odds ratio [OR] 9.32), history of polyps (OR 4.54) and rectal bleeding (OR 1.73). Indications for which FS was least useful were: change in bowel habit (OR 0.22), diarrhoea (OR 0.46) and constipation (OR 0.38). CONCLUSIONS: LGI investigation in frail elderly patients can be rationalised according to indication. Performing FS and MPCT together is not always necessary.


Assuntos
Doenças do Colo/diagnóstico , Idoso Fragilizado , Satisfação do Paciente , Melhoria de Qualidade , Sigmoidoscopia/métodos , Tomografia Computadorizada Espiral/métodos , Idoso , Feminino , Humanos , Masculino , Estudos Retrospectivos
18.
J Obstet Gynaecol ; 31(7): 603-7, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21973132

RESUMO

A meta-analyses of endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) gene polymorphisms in pre-eclampsia was performed. We shortlisted 33 studies (17 for ACE; 16 for eNOS gene polymorphisms), of which 29 articles (16 for ACE and 15 for eNOS) were analysed. Overall, 1,620 cases with pre-eclampsia and 2,158 controls were analysed for intron 16 insertion-deletion polymorphism in ACE gene. A total of 1,610 subjects with pre-eclampsia and 2,875 controls were analysed for the Glu298Asp in eNOS gene. Overall, the random-effects odds ratio (OR) with Glu298Asp in eNOS gene was 0.958 (95% confidence intervals, CI 0.747-1.228, p > 0.05), and for the insertion-deletion/ACE polymorphism was 0.987 (95% CI 0.698-1.395, p > 0.05). Significant heterogeneity was observed in the studies that evaluated polymorphisms in ACE (Q value = 55.6; I(2) = 73; p value = 0.000); and eNOS (Q value = 37.2; I(2) = 62.4; p value = 0.001) polymorphisms. No significant risk of pre-eclampsia was observed in both eNOS and ACE genes with these polymorphisms.


Assuntos
Predisposição Genética para Doença/genética , Óxido Nítrico Sintase Tipo III/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético/genética , Pré-Eclâmpsia/genética , Feminino , Deleção de Genes , Humanos , Mutagênese Insercional/genética , Razão de Chances , Gravidez
19.
Clin Cancer Res ; 15(21): 6732-9, 2009 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-19843663

RESUMO

PURPOSE: Inhibiting mammalian target of rapamycin (mTOR) signaling in acute myelogenous leukemia (AML) blasts and leukemic stem cells may enhance their sensitivity to cytotoxic agents. We sought to determine the safety and describe the toxicity of this approach by adding the mTOR inhibitor, sirolimus (rapamycin), to intensive AML induction chemotherapy. EXPERIMENTAL DESIGN: We performed a phase I dose escalation study of sirolimus with the chemotherapy regimen MEC (mitoxantrone, etoposide, and cytarabine) in patients with relapsed, refractory, or untreated secondary AML. RESULTS: Twenty-nine subjects received sirolimus and MEC across five dose levels. Dose-limiting toxicities were irreversible marrow aplasia and multiorgan failure. The maximum tolerated dose (MTD) of sirolimus was determined to be a 12 mg loading dose on day 1 followed by 4 mg/d on days 2 to 7, concurrent with MEC chemotherapy. Complete or partial remissions occurred in 6 (22%) of the 27 subjects who completed chemotherapy, including 3 (25%) of the 12 subjects treated at the MTD. At the MTD, measured rapamycin trough levels were within the therapeutic range for solid organ transplantation. However, direct measurement of the mTOR target p70 S6 kinase phosphorylation in marrow blasts from these subjects only showed definite target inhibition in one of five evaluable samples. CONCLUSIONS: Sirolimus and MEC is an active and feasible regimen. However, as administered in this study, the synergy between MEC and sirolimus was not confirmed. Future studies are planned with different schedules to clarify the clinical and biochemical effects of sirolimus in AML and to determine whether target inhibition predicts chemotherapy response.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Sirolimo/administração & dosagem , Adulto , Idoso , Carboplatina/uso terapêutico , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/uso terapêutico , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Proteínas Quinases/metabolismo , Recidiva , Transdução de Sinais , Sirolimo/efeitos adversos , Sirolimo/metabolismo , Serina-Treonina Quinases TOR
20.
Clin Vaccine Immunol ; 16(11): 1587-94, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19741090

RESUMO

Many currently available diagnostic tests for typhoid fever lack sensitivity and/or specificity, especially in areas of the world where the disease is endemic. In order to identify a diagnostic test that better correlates with typhoid fever, we evaluated immune responses to Salmonella enterica serovar Typhi (serovar Typhi) in individuals with suspected typhoid fever in Dhaka, Bangladesh. We enrolled 112 individuals with suspected typhoid fever, cultured day 0 blood for serovar Typhi organisms, and performed Widal assays on days 0, 5, and 20. We harvested peripheral blood lymphocytes and analyzed antibody levels in supernatants collected on days 0, 5, and 20 (using an antibody-in-lymphocyte-supernatant [ALS] assay), as well as in plasma on these days. We measured ALS reactivity to a serovar Typhi membrane preparation (MP), a formalin-inactivated whole-cell preparation, and serovar Typhi lipopolysaccharide. We measured responses in healthy Bangladeshi, as well as in Bangladeshi febrile patients with confirmed dengue fever or leptospirosis. We categorized suspected typhoid fever individuals into different groups (groups I to V) based on blood culture results, Widal titer, and clinical features. Responses to MP antigen in the immunoglobulin A isotype were detectable at the time of presentation in the plasma of 81% of patients. The ALS assay, however, tested positive in all patients with documented or highly suspicious typhoid, suggesting that such a response could be the basis of improved diagnostic point-of-care-assay for serovar Typhi infection. It can be important for use in epidemiological studies, as well as in difficult cases involving fevers of unknown origin.


Assuntos
Anticorpos Antibacterianos/análise , Anticorpos Antibacterianos/sangue , Imunoglobulina A/sangue , Linfócitos/imunologia , Salmonella typhi/imunologia , Febre Tifoide/diagnóstico , Febre Tifoide/imunologia , Adolescente , Adulto , Bangladesh , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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