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Objective: To investigate the value of a nomogram predicting the outcome of intracerebral hemorrhage (ICH) based on clinical characteristics and diffusion-weighted imaging (DWI) of hyperintense lesions. Methods: A case-control study. Consecutive patients, aged 30-88(59±13) years old, with ICH were recruited at the Stroke Center of Zhengzhou People's Hospital from January 2018 to August 2021. Patients were divided into a group with DWI lesions and a group without DWI lesions depending on whether there were DWI hyperintense lesions distant from the hematoma. Prognosis was evaluated at 90 days via the modified Rankin Scale (mRS). Univariate and multivariable logistic regression models were used to identify independent predictors of a poor ICH outcome (mRS score≥4), and a nomogram model was developed. The performance of the nomogram was validated via the area under the receiver operating characteristic curve (AUC) and a calibration chart. Results: Of the 303 patients included in the study, 24.8% presented with DWI lesions; 17.5% with asymptomatic DWI lesions and 7.3% with symptomatic DWI lesions. Poor outcomes were significantly more frequent in the group with DWI lesions than in the group without DWI lesions (χ2=21.32, P<0.001). In multivariable regression analysis, age [odds ratio (OR)=1.032, 95% confidence interval (CI) 1.002-1.063, P=0.035], hematoma volume (OR=1.050, 95%CI 1.011-1.090, P=0.012), hematoma location (OR=3.839, 95%CI 1.248-11.805, P=0.019), DWI lesions (OR=3.955, 95%CI 1.906-8.206, P<0.001), and baseline NIHSS scores (OR=1.102, 95%CI 1.038-1.170, P=0.001) were independent predictors of a poor outcome. In subgroup analysis patients with asymptomatic DWI lesions had a 3-fold greater risk of a poor outcome compared to those without DWI lesions (OR=3.135, 95%CI 1.382-7.112, P=0.006), and patients with symptomatic DWI lesions had a 7-fold greater risk of a poor outcome compared to those without DWI lesions (OR=7.126, 95%CI 2.279-22.277, P=0.001). A nomogram model was established based on the independent predictors for a poor outcome. The AUC of the nomogram was 0.846 (95%CI 0.795-0.898), and a calibration chart indicated good consistency between values predicted by the nomogram and actual observed values. Conclusions: DWI lesions are an independent risk factor for a poor outcome in patients with ICH-particularly symptomatic DWI lesions. A nomogram model based on clinical characteristics and DWI lesions exhibited good efficacy when predicting the outcome of ICH.
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A 3-month-old infant patient presented with a 1-week history of a quickly progressive mass in the left eye. A hard, irregularly shaped tumor was found in the superolateral orbit. B-scan showed an uneven hypoecho and an undefined lesion. On the orbital CT, a soft tissue mass was located around the left zygomatic tubercle, involving part of the bone and lacrimal gland. The left orbital mass was removed under general anesthesia after admission. The histological and immunohistochemical examination revealed it was a melanotic neuroectodermal tumor. The infant patient was followed up for 6 months after the operation, and no recurrence was found. (Chin J Ophthalmol, 2021, 57: 372-374).
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Aparelho Lacrimal , Tumor Neuroectodérmico Melanótico , Doenças Orbitárias , Humanos , Lactente , Recidiva Local de Neoplasia , Tumor Neuroectodérmico Melanótico/diagnóstico por imagem , Tumor Neuroectodérmico Melanótico/cirurgia , ÓrbitaRESUMO
The aim of this study was to investigate the prognostic value of the prognostic nutritional index (PNI) on the long-term survival of non-small cell lung cancer (NSCLC) patients who received platinum-based chemotherapy. Data on nutritional parameters and clinicopathological characteristics [e.g., albumin, total protein, body mass index (BMI), eastern cooperative oncology group (ECOG) performance status, stage, pathology, treatment strategy] were analyzed and retrospectively correlated with overall survival (OS). The PNI was calculated based on the concentration of albumin and lymphocyte count [10 × albumin, (g/dl) + 0.005 × lymphocyte (count/mm3)]. A receiver operating characteristic curve (ROC) analysis was used to find the optimal cut-off value of PNI. Univariate and multivariate analyses were used to evaluate the prognostic value of PNI. A total of 186 patients met the inclusion criteria. The optimal cut-off value for PNI was 50.45. Compared with the parameters of the low PNI group (n=76), high PNI was significantly associated with adenocarcinoma type, stage III, better ECOG and comprehensive treatment modality. The univariate analysis demonstrated that OS was superior when PNI ≥50.45, albumin ≥35 g/l, platelet-lymphocyte ratio (PLR) ≥163 and ECOG <2, and when the patient received a comprehensive treatment modality. In the multivariate analysis, PNI, TNM stage and treatment strategy were identified as independent predictors of survival in this study. This retrospective study demonstrated that a low PNI was related to worse overall survival in patients with stage III/IV NSCLC who received platinum-based chemotherapy. These data provided a conceptual basis for further research on the clinical application of the PNI index for patients receiving chemotherapy for intermediate- and advanced-stage NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Avaliação Nutricional , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Contagem de Linfócitos , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
Objective: To study the correlations between the distance stereoacuity and the levels of control at different far distance fixations in children with intermittent exotropia. Methods: In this prospective, non-interventional case series study, 52 children with intermittent exotropia (basic, divergence excess and pseudo-divergence excess types, exodeviation angles≥15 PD) admitted to the Shandong Provincial Hospital Affiliated to Shandong University for surgery between August 2014 and March 2015 were enrolled. The distance stereoacuity was tested with the distance Randot stereotest, and the control of exodeviation was assessed at outdoor far distance fixation of 50 m, indoor far distance fixation of 30 m, and indoor distance fixation of 3 m, respectively, using the office-based 6-point control scale proposed by Mohney and Holmes. The distance stereoacuity and control scores of every intermittent exotropia child were tested 3-4 times in a single day with an interval of at least 2 hours. Nonparametric Spearman rank method was used to analyze the correlations between distance stereoacuity and levels of control at three different far distances in children with intermittent exotropia. Results: The mean age of 52 enrolled children (26 males, 26 females) was 7 years (range, 5-12 years), and 192 groups of distance stereoacuity and control scores were got for the 52 children. Positive correlations between the distance stereoacuity and the levels of control at outdoor far distance fixation of 50 m, indoor far distance fixation of 30 m, and indoor distance fixation of 3 m were observed (coefficients of correlations; r=0.489, 0.472, 0.282, all P<0.001). Conclusion: There are correlations between the distance stereoacuity and the levels of control at outdoor far distance fixation of 50 m, indoor far distance fixation of 30 m and indoor distance fixation of 3 m in children with intermittent exotropia, and the former two are found to be stronger than the latter one. (Chin J Ophthalmol, 2019, 55:25-30).
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Exotropia , Criança , Pré-Escolar , Percepção de Profundidade , Exotropia/diagnóstico , Exotropia/fisiopatologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Testes Visuais , Acuidade VisualRESUMO
Objective: To investigate the clinical features and surgical outcomes of patients with acute acquired concomitant esotropia (AACE) type â ¡(AACE-â ¡) and type â ¢ (AACE-â ¢). Methods: Retrospective case series analysis. Medical records of consecutive patients who underwent strabismus surgery for AACE-â ¡ and AACE-â ¢ in Shandong Provincial Hospital affiliated to Shandong University between January 2011 and June 2016 with a minimum follow-up time of 3 months were collected. Each patient underwent a complete ophthalmological and orthoptic examination to exclude esotropia resulting from other reasons, and a systemic assessment to exclude AACE related to intracranial and systemic diseases. Surgical procedures were determined according to the esodeviations measured at distance and near and the different dominant eye of patients. A successful surgical alignment was defined as the distant and near deviation in the primary gaze within 8 prism diopters (PD) of orthophoria and no diplopia. Results: Twenty-nine patients were enrolled in this study, including 17 males and 12 females. The mean age of the patients was 22.14±15.13 years (range, 5-63 years). The median corrected visual acuity (LogMAR) of patients with AACE-â ¡was 0 (range, 0.22 to 0), and that of patients with AACE-â ¢ was 0 (range, 0.10 to 0). The median esodeviation of patients with AACE-â ¡ at distance was 35 PD (range, 10 to 55 PD), and that at near was 35 PD (range, 20 to 60 PD). The median esodeviation of patients with AACE-â ¢ at distance was 30 PD (range, 12 to 50 PD), and that at near was 30 PD (range, 6 to 50 PD). When tested with the red filter test preoperatively, all the patients had an uncrossed horizontal diplopia with the same distance in left and right lateral fixations. With a mean follow-up time of 12.0±12.6 months, of all the 29 patients, 24 patients (83%) achieved successful surgical alignment after one surgery, and 5 patients (17%) were undercorrected or had recurrence, in whom 4 were successfully aligned after repeated surgery (performed at a mean of 3.5 months after the first surgery) and 1 was treated with the Fresnel press-on prism. At the last follow-up, of all the 28 patients successfully aligned, 20 (71%) regained bifoveal fusion, 8 (29%) regained peripheral fusion, 17 (61%) regained normal stereopsis (stereoacuity ≤60"), and 11 regained a certain degree of stereopsis (stereoacuity 80"-400"). The constituent ratio of biocular central fusion and peripheral fusion in patients with AACE-â ¡ had no significant difference from patients with AACE-â ¢ (χ(2)=0.235, P>0.05), and the constituent ratio of central stereopsis, macular stereopsis, and peripheral stereopsis in patients with AACE-â ¡ had no significant difference from patients with AACE-â ¢ (χ(2)=0.762, P>0.05). Conclusions: All patients exhibited the typical features of AACE, which included an acute onset of diplopia and comitant esotropia, a wide range of onset age of the patients, normal corrected visual acuity and ocular movements, a mean moderate level of esodeviation with a wide range, and a good binocular potential. According to the esodeviations measured at distance and near and the different dominant eye of patients, good oculomotor alignment and perceptual outcomes may be obtained in patients with AACE-â ¡and AACE-â ¢. (Chin J Ophthalmol, 2017, 53: 908-916).
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Esotropia , Procedimentos Cirúrgicos Oftalmológicos , Adolescente , Adulto , Criança , Pré-Escolar , Esotropia/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculos Oculomotores , Estudos Retrospectivos , Resultado do Tratamento , Visão Binocular , Adulto JovemRESUMO
BACKGROUND: Zerumbone (ZER) is a phytochemical that appears to regulate cell proliferation and apoptosis. It has been reported to have an anti-tumour effect in various malignant cells; however, the effect and the mechanism of ZER on melanoma cells needs to be clarified. AIM: To explore whether ZER has an effect on human melanoma cells and to identify the mechanisms involved. METHODS: We determined the chemotherapeutic action of ZER on the human malignant melanoma (MM) A375 cell line by CCK-8 immunohistochemistry, Hoechst 33342 staining and flow cytometry analysis. We also investigated the signalling pathways by which ZER induces apoptosis in A375 cells, using western blotting, reverse transcription PCR and caspase-3 activity analysis. RESULTS: ZER induced significant cytotoxic action in A375 cells. Hoechst 33342 staining and flow cytometry apoptosis analysis further demonstrated that ZER induced apoptosis in A375 cells. Treatment with ZER downregulated Bcl-2 gene and protein levels, upregulated Bax and Cytochrome c gene and protein levels, and activated Caspase-3. CONCLUSIONS: ZER might have a chemotherapeutic effect on human melanoma cells through mitochondria-mediated pathways.
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Antineoplásicos/farmacologia , Melanoma/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Sesquiterpenos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Caspase 3/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Melanoma/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacosRESUMO
Superficial fungal infections (SFIs) are characterized by diverse etiologies, complex pathogenesis, and marked geographical differences in patient symptoms. Conventional management of SFIs is associated with complications such as hepatotoxicity, skin problems, severe headaches, and clinical difficulties including intractable relapses and drug-drug interactions in patients with chronic diseases remain to be addressed. Moreover, in topical treatment, low penetration of antifungal drugs in hard tissues such as finger (toe) nails and drug-resistant fungi are emerging concerns in current antifungal therapy. Nanotechnology has been a leading research topic in recent years for new dosing forms of antifungal drugs, chemical modification of traditional drugs, and pharmacokinetic improvement, providing potential opportunities for the effective treatment of SFIs. The present study reviewed the direct use of nanoparticles in SFIs and the use of nanoparticles as carriers in SFIs and discussed their future medicinal applications. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/01-12915-PM-29863.jpg.
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Dermatomicoses , Nanopartículas , Humanos , Antifúngicos , Dermatomicoses/tratamento farmacológico , Dermatomicoses/microbiologia , Fungos , Administração TópicaRESUMO
The pathogenesis of Acanthamoeba keratitis (AK) is complicated. In our previous studies, TLR4 was found involved in the process of infection by Acanthamoeba in human corneal cells. The purpose of this study was to investigate the role of Toll-like receptor 4 (TLR4) signalling pathway in Wistar rats challenged with Acanthamoeba. The rat model of AK was established. Corneas were collected and analysed by real-time PCR to assess the mRNA levels of TLR 2, 4, myeloid differentiation protein (MyD)88, nuclear factor (NF)-κB, extracellular signal-regulated kinase (ERK), interleukin (IL)-8, tumour necrosis factor (TNF)-α and interferon (IFN) -ß. Immunocytochemistry and Western blot were conducted to examine the proteins of TLR2, TLR4, p-Erk1/2 and p-IκB. Specific inhibitors PDTC and U0126 were used to pretreat the animals to determine the exact receptor and signalling pathway involved in pathogenesis. Expressions of TLR4, MyD88, all three cytokines, NF-κB, p-IκB and p-Erk1/2 were increased in Acanthamoeba-treated rat corneas. PDTC inhibited the production of IL-8 and TNF-α, while U0126 inhibited the synthesis of IFN-ß. TLR4 was involved in sensing the challenge of Acanthamoeba and inducing production of cytokines through TLR4-NF-κB and TLR4-Erk1/2 pathways in corneas of Wistar rats.
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Ceratite por Acanthamoeba/imunologia , Acanthamoeba/imunologia , Córnea/imunologia , Epitélio Corneano/imunologia , Interferon beta/imunologia , Interleucina-8/imunologia , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Transdução de Sinais , Receptor 2 Toll-Like , Receptor 4 Toll-Like , Fator de Necrose Tumoral alfa/imunologia , Acanthamoeba/metabolismo , Ceratite por Acanthamoeba/metabolismo , Animais , Western Blotting , Córnea/parasitologia , Córnea/fisiopatologia , Córnea/ultraestrutura , Modelos Animais de Doenças , Epitélio Corneano/parasitologia , Epitélio Corneano/fisiopatologia , Epitélio Corneano/ultraestrutura , Humanos , Imuno-Histoquímica , Interferon beta/biossíntese , Interleucina-8/biossíntese , NF-kappa B/imunologia , NF-kappa B/metabolismo , Reação em Cadeia da Polimerase , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Receptor 2 Toll-Like/imunologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Objective: Transanal total mesorectal excision (taTME) was a very hot topic in the first few years since its appearance, but now more introspections and controversies on this procedure have emerged. One of the reasons why the Norwegian Ministry of Health stopped taTME was the high incidence of postoperative anastomotic leak. In current study, the incidence and risk factors of anastomotic leak after taTME were analyzed based on the data registered in the Chinese taTME Registry Collaborative (CTRC). Methods: A case-control study was carried out. Between November 15, 2017 and December 31, 2020, clinical data of 1668 patients undergoing taTME procedure registered in the CTRC database from 43 domestic centers were collected retrospectively. After excluding 98 cases without anastomosis and 109 cases without complete postoperative complication data, 1461 patients were finally enrolled for analysis. There were 1036 males (70.9%) and 425 females (29.1%) with mean age of (58.2±15.6) years and mean body mass index of (23.6±3.8) kg/m(2). Anastomotic leak was diagnosed and classified according to the International Study Group of Rectal Cancer (ISREC) criteria. The risk factors associated with postoperative anastomotic leak cases were analyzed. The impact of the cumulative number of taTME surgeries in a single center on the incidence of anastomotic leak was evaluated. As for those centers with the number of taTME surgery ≥ 40 cases, incidence of anastomic leak between 20 cases of taTME surgery in the early and later phases was compared. Results: Of 1461 patients undergoing taTME, 103(7.0%) developed anastomotic leak, including 71 (68.9%) males and 32 (31.1%) females with mean age of (59.0±13.9) years and mean body mass index of (24.5±5.7) kg/m(2). The mean distance between anastomosis site and anal verge was (2.6±1.4) cm. Thirty-nine cases (37.9%) were classified as ISREC grade A, 30 cases (29.1%) as grade B and 34 cases (33.0%) as grade C. Anastomotic leak occurred in 89 cases (7.0%,89/1263) in the laparoscopic taTME group and 14 cases (7.1%, 14/198) in the pure taTME group. Multivariate analysis showed that hand-sewn anastomosis (P=0.004) and the absence of defunctioning stoma (P=0.013) were independently associated with anastomotic leak after taTME. In the 16 centers (37.2%) which performed ≥ 30 taTME surgeries with cumulative number of 1317 taTME surgeries, 86 cases developed anastomotic leak (6.5%, 86/1317). And in the 27 centers which performed less than 30 taTME surgeries with cumulative number of 144 taTME surgeries, 17 cases developed anastomotic leak (11.8%, 17/144). There was significant difference between two kinds of center (χ(2)=5.513, P=0.019). Thirteen centers performed ≥ 40 taTME surgeries. In the early phase (the first 20 cases in each center), 29 cases (11.2%, 29/260) developed anastomotic leak, and in the later phase, 12 cases (4.6%, 12/260) developed anastomotic leak. The difference between the early phase and the later phase was statistically significant (χ(2)=7.652, P=0.006). Conclusion: The incidence of anastomotic leak after taTME may be reduced by using stapler and defunctioning stoma, or by accumulating experience.
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Laparoscopia , Neoplasias Retais , Adulto , Idoso , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/cirurgia , Reto/cirurgia , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To evaluate the effect of individualized antiplatelet therapy based on CYP2C19 genotype and platelet function on the prognosis of patients after percutaneous coronary intervention (PCI) compared with conventional antiplatelet therapy. PATIENTS AND METHODS: Patients diagnosed with acute coronary syndromes (ACS) in Shandong Provincial Qianfoshan Hospital from December 2014 to December 2017 were included in this prospective study and randomly divided into conventional (CA) and individualized antiplatelet therapy group (IA) at 1:1 ratio. Patients in the CA group received clopidogrel 75 mg once a day (QD). Group IA was divided into extensive, intermediate, and poor metabolizers according to the results of the CYP2C19 gene test. Three genotypes were given clopidogrel 75 mg QD, 75 mg twice daily (BID) and ticagrelor 90 mg BID respectively. After taking these medicines for a period of time, platelet function was monitored by thromboelastography (TEG) and MAADP values were recorded. MAADP indicates the adenosine diphosphate (ADP) induced platelet function that not inhibited by medicine. High platelet reactivity (HPR) was defined as MAADP > 47mm, indicating a high risk of thrombus, and MAADP ≤ 31 mm indicates a high risk of hemorrhage. For extensive metabolizers (EMs) and intermediate metabolizers (IMs) patients with HPR, the antiplatelet therapy would be changed by the clinician according to the patient's conditions. Major adverse cardiovascular events (MACE) and hemorrhage events were monitored during 1-year follow-up. RESULTS: The patients with MAADP > 47 mm were 89 (28.6%) in the IA group. There were 50 EMs patients with MAADP > 47 mm (33.3%). Of which, there were 2 cases which changed the dosage of clopidogrel to 75 mg BID, 14 cases who changed clopidogrel to ticagrelor. There were 36 IMs patients with MAADP > 47 mm (30.8%). Of which, there were 19 cases who changed clopidogrel to ticagrelor. There was no significant difference in the value of MAADP between EMs and IMs patients. Within 1 year after PCI, the occurrence of MACE in the IA group was significantly lower than that in the CA group (p=0.010). CONCLUSIONS: (1) Patients with a CYP2C19 loss-of-function (LOF) gene who take double doses of clopidogrel overcome the decreased efficacy of clopidogrel which partly due to CYP2C19 LOF gene, without increasing the risk of hemorrhage. (2) Individualized antiplatelet therapy based on CYP2C19 genotype and platelet function can significantly reduce the occurrence of MACE (mainly acute non-fatal myocardial infarction) after PCI without increasing the risk of moderate or severe hemorrhage.
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Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/farmacologia , Citocromo P-450 CYP2C19/genética , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/farmacologia , Ticagrelor/farmacologia , Síndrome Coronariana Aguda/diagnóstico , Plaquetas/efeitos dos fármacos , Clopidogrel/administração & dosagem , Citocromo P-450 CYP2C19/metabolismo , Relação Dose-Resposta a Droga , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Testes de Função Plaquetária , Ticagrelor/administração & dosagemRESUMO
The serum concentration of erythropoietin in 79 cases with various blood diseases, uremia, chronic obstructive pulmonary disease etc was determined. At comparable degrees of anemia, patients with myelodysplastic syndrome and aplastic anemia had the highest levels of erythropoietin in our study. The high level of erythropoietin titer in patients with aplastic anemia should be taken as the nom for renal synthesis and release of this hormone. The erythropoietin level in patients with uremic anemia was lower than the level in patients with anemia of other causes but still higher than that of the normal controls. Patients suffering from polycystic kidney disease with or without uremia had a high level of erythropoietin due to local hypoxia of remnant kidney tissue resulting from the pressure of cystic formation. Different methods are used to determine the erythropoietin level, which varies with the stage and etiology of the diseases. There are other stimulating or inhibitory factors of erythropoiesis when the assay is processed. Transfusion and administration of certain drugs also influence the growth of erythroid cells, thus the serum titers of erythropoietin differed markedly between patients at comparable hemoglobin concentration.
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Anemia Aplástica/sangue , Eritropoetina/sangue , Adolescente , Adulto , Idoso , Criança , Feminino , Hemoglobinas/análise , Humanos , Pneumopatias Obstrutivas/sangue , Masculino , Pessoa de Meia-Idade , Uremia/sangueRESUMO
The family size biogas tanks were built in the study site. Their effects were monitored. Faecal coliform and parasite eggs were examined before and after biogas digestion. The results of whole-year operation indicate that faecal coliform and parasite eggs can be reduced by 99.7% and 99.8%, respectively. The schistosome eggs survival experiment showed that the eggs all died off in 100 days of retention in biogas tanks. Therefore, the appropriate technology of nightsoil treatment can effectively interrupt the life cycle of schistosome.
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Fezes/microbiologia , Contagem de Ovos de Parasitas/métodos , Schistosoma/isolamento & purificação , Esquistossomose/microbiologia , Animais , Esquistossomose/epidemiologia , SoloAssuntos
Diarreia/tratamento farmacológico , Loperamida/farmacologia , Piperidinas/farmacologia , Contração Uterina/efeitos dos fármacos , Animais , Carboprosta/antagonistas & inibidores , Carboprosta/farmacologia , Diarreia/induzido quimicamente , Feminino , Loperamida/uso terapêutico , Masculino , Camundongos , Contração Muscular/efeitos dos fármacos , RatosRESUMO
Fifty-eight acute promyelocytic leukemia (APL) patients (11 newly diagnosed and 47 relapsed) were studied for arsenic trioxide (As2O3) treatment. Clinical complete remission (CR) was obtained in 8 of 11 (72.7%) newly diagnosed cases. However, As2O3 treatment resulted in hepatic toxicity in 7 cases including 2 deaths, in contrast to the mild liver dysfunction in one third of the relapsed patients. Forty of forty-seven (85.1%) relapsed patients achieved CR. Two of three nonresponders showed clonal evolution at relapse, with disappearance of t(15;17) and PML-RARalpha fusion gene in 1 and shift to a dominant AML-1-ETO population in another, suggesting a correlation between PML-RARalpha expression and therapeutic response. In a follow-up of 33 relapsed cases over 7 to 48 months, the estimated disease-free survival (DFS) rates for 1 and 2 years were 63.6% and 41.6%, respectively, and the actual median DFS was 17 months. Patients with white blood cell (WBC) count below 10 x 10(9)/L at relapse had better survival than those with WBC count over 10 x 10(9)/L (P =.038). The duration of As2O3-induced CR was related to postremission therapy, because there was only 2 of 11 relapses in patients treated with As2O3 combined with chemotherapy, compared with 12 of 18 relapses with As2O3 alone (P =.01). Reverse transcription polymerase chain reaction (RT-PCR) analysis in both newly diagnosed and relapsed groups showed long-term use of As2O3 could lead to a molecular remission in some patients. We thus recommend that ATRA be used as first choice for remission induction in newly diagnosed APL cases, whereas As2O3 can be either used as a rescue for relapsed cases or included into multidrug consolidation/maintenance clinical trials.