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1.
Zhonghua Yu Fang Yi Xue Za Zhi ; 57(8): 1266-1270, 2023 Aug 06.
Artigo em Chinês | MEDLINE | ID: mdl-37574322

RESUMO

To evaluate the effectiveness of intervention plans developed by the evidence base multi-discipline critical strategies (EBPCS) on temperature and clinical outcomes in very preterm infants (VPIs) born at<32 weeks. Clinical data were collected from VPIs born in the delivery room/operating room of Chengdu Women's and Children's Central Hospital from May 1, 2021, to May 31, 2022, who required immediate temperature management and were transferred to the neonatal intensive care unit (NICU) of the hospital. The study population was randomly divided into a control group and an intervention group based on the random number table method, with 108 cases in each group. The control group implemented the conventional temperature management recommended by domestic guidelines, while the intervention group adopted EBPCS interventions compared to the control group. The differences in body temperature and clinical outcomes between the two groups were compared after the implementation of different temperature management strategies. A total of 216 VPIs were included. The intervention group had a lower incidence of hypothermia (30.55% vs. 87.03%, P<0.001), higher mean body temperature admitted to the NICU [(36.56±0.31) ℃ vs. (35.77±0.53) ℃, P<0.001], a lower dose of pulmonary surfactant [(115.94±36.96) mg/kg vs. (151.41±54.68) mg/kg, P=0.014], shorter duration of mechanical ventilation [(5.77±1.26) days vs. (14.19±4.63) days, P=0.006], and lower incidence of intraventricular haemorrhage (12.04% vs. 23.15%, P=0.032). The implementation of temperature intervention strategies developed by the EBPCS for VPIs after birth could prevent and reduce the incidence of hypothermia and improve clinical outcomes.


Assuntos
Hipotermia , Recém-Nascido Prematuro , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Febre , Hipotermia/prevenção & controle , Recém-Nascido de muito Baixo Peso , Temperatura
2.
Climacteric ; 25(4): 421-424, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35504301

RESUMO

OBJECTIVE: This article reports the first live birth after cryopreserved ovarian tissue transplantation to prevent premature ovarian insufficiency in China. METHODS: A patient with myelodysplastic syndrome received ovarian tissue cryopreservation before hematopoietic stem cell transplantation, and six ovarian cortex strips were thawed and transplanted into her peritoneal pocket 2 years later. RESULTS: Pregnancy occurred spontaneously 27 months after grafting, and a healthy girl was born at 38 weeks gestation. Until now, the child has developed normally without any major diseases. CONCLUSIONS: We report the first live birth resulting from ovarian tissue cryopreservation and transplantation in China.


Assuntos
Preservação da Fertilidade , Menopausa Precoce , Insuficiência Ovariana Primária , Criança , Criopreservação/métodos , Feminino , Preservação da Fertilidade/métodos , Humanos , Nascido Vivo , Gravidez , Insuficiência Ovariana Primária/prevenção & controle
3.
Climacteric ; 24(1): 68-73, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32729333

RESUMO

Menopause-related symptoms are common problems of middle-aged women that can seriously affect their quality of life. Menopausal hormone therapy (MHT) for climacteric symptoms is the first choice recommended by the International Menopause Society and likewise by other societies and institutions covering this field. However, non-hormonal therapies can be an alternative effective option, especially for women who are not suitable for MHT. Acupuncture is one of the most important methods. With deepening experience of the use of traditional Chinese acupuncture and moxibustion in the improvement of menopause symptoms, more clinical evidence has been obtained to support the effectiveness and safety of this treatment concept that is very often used in China. This review summarizes the evidence for effective treatment of climacteric complaints by acupuncture in recent years, shares the clinical experience of the authors of this review, all of whom head or work in units with daily large numbers of outpatients, and includes, in particular, results from studies performed in the Department of Acupuncture--Moxibustion of Tsinghua University Chuiyangliu Hospital, Beijing, China. In addition, there is a summary about the safety of acupuncture treatment in traditional Chinese medicine.


Assuntos
Terapia por Acupuntura , Fogachos/terapia , Menopausa , Povo Asiático , China , Feminino , Humanos , Medicina Tradicional Chinesa
4.
Climacteric ; 24(6): 624-628, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34374311

RESUMO

OBJECTIVE: This article reports the first case of pregnancy after frozen-thawed ovarian tissue transplantation to prevent iatrogenic premature ovarian insufficiency in China. METHODS: Ovarian tissue cryopreservation was performed in a patient with myelodysplastic syndrome (MDS) before multi-agent chemotherapy and hematopoietic stem cell transplantation. Two years later, she showed complete remission from MDS, and six frozen-thawed ovarian tissue strips were transplanted into the peritoneal pocket. RESULTS: The patient's ovarian activity was restored 3 months after transplantation, and pregnancy occurred spontaneously 27 months after grafting. Until now, the pregnancy has progressed for 30 weeks, and the repeated ultrasound showed normal fetal development. CONCLUSION: This is the first pregnancy resulting from ovarian tissue cryopreservation and transplantation in China.


Assuntos
Ovário , Gravidez , Insuficiência Ovariana Primária , Transplante de Tecidos , China , Feminino , Humanos
5.
Zhonghua Fu Chan Ke Za Zhi ; 54(1): 33-37, 2019 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-30695904

RESUMO

Objective: To study perioperative period conditions of total and partial colpocleisis with severe pelvic organ prolapse (POP) in elderly patients. Methods: From Jan. 2014 to Oct. 2017 286 severe POP elderly patients underwent total or partial colpocleisis. The mean age was (76.0±5.1) years (60-90 years) . Of which, 220 patients (76.9%, 220/286) presented more than one kind of medical disease. The operative time, intraoperative blood loss, hospital stay after surgery, postoperative complications, preoperative urinary dysuria symptoms of total and partial colpocleisis in treatment of 286 patients were analyzed. Results: In 286 patients, 172 patients (60.1%) underwent total colpocleisis and 114 patients (39.9%) underwent partial colpocleisis. Totally 48 patients (16.8%) in 286 patients underwent anti-urinary incontinence procedure. The mean operating time of 286 patients was (67±22) minutes,the mean blood loss was (52± 57) ml, the mean hospital stay after surgery was (5.9±1.9) days (2-16 days) . The rate of postoperative complications was 8.7% (25/286) . Those complications including 1 case of bladder injury during operation, 3 cases of postoperative pelvic hematoma, 1 case of intestinal obstruction, 5 cases of atrial fibrillation, 10 cases of postoperative morbidity, 3 cases of pulmonary embolism, 1 case of lower limb thrombosis, 1 case of urinary retention underwent electrical stimulation treatment because of ineffective application of urinary retention catheter. The mean operating time was (67±22) minutes in total colpocleisis and (68±20) minutes in partial colpocleisis (P>0.05) , the mean blood loss was (58±62) ml in total colpocleisis and (41±45) ml in partial colpocleisis (P>0.05) , the mean hospital stay after surgery was (5.9±1.9) days in total colpocleisis and (6.0±1.8) days in partial colpocleisis (P>0.05) , the rate of post operative complications was 8.1%(14/172) in total colpocleisis and 9.6% (11/114) in partial colpocleisis (P>0.05) , respectively; those four of comparisons showed no significant difference. There were 129 patients (45.1%, 129/286) with voiding difficulty before surgery; the mean postvoid residual volumes of the above two operation types of people after operation were (35±43) and (34±41) ml, which showed no significant difference (P>0.05) . Conclusions: Colpocleisis is a safe and effective management in selected elderly patients with severe POP, who no longer desire to maintain vaginal coital function. There is no significant difference in the perioperative period conditions between total and partial colpocleisis. The choice of surgical procedure is based on factors such as the presence or absence of malignancy in the uterus, age and willingness of the patient, and general condition.


Assuntos
Colpotomia/efeitos adversos , Prolapso de Órgão Pélvico/cirurgia , Incontinência Urinária/etiologia , Retenção Urinária , Idoso , Idoso de 80 Anos ou mais , Colpotomia/métodos , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Histerectomia , Pessoa de Meia-Idade , Prolapso de Órgão Pélvico/patologia , Resultado do Tratamento , Vagina/patologia , Vagina/cirurgia
6.
Genet Mol Res ; 15(4)2016 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-27886341

RESUMO

This study explored the effects of levothyroxine (L-T4) replacement therapy on pregnancy outcomes in patients with subclinical hypothyroidism (SCH). We analyzed the effects on pregnancy outcomes with respect to gestational week when the desired thyroid-stimulating hormone (TSH) level was reached as well as the length of time required to reach the target level during L-T4 treatment. This study enrolled 457 patients diagnosed with SCH upon initial thyroid function screening. Subjects were assigned to the treatment group (N = 184), and the control group (N = 273). Two variables were analyzed in the treatment group: the gestational week when the target TSH level was achieved and the length of time required to reach the target level during treatment. Based on these criteria, the treatment group was further divided into subgroups, including three subgroups based on the time required to reach target levels (<4 weeks, 4-8 weeks, and >8 weeks) and gestational week when the target TSH level was achieved (before the 12th, between the 12th-28th, and after the 28th gestational week). The overall risk of complications in the control group was significantly higher than in the treatment group (P < 0.05). After L-T4 treatment, the incidences of premature rupture of fetal membranes (PROM), gestational diabetes mellitus, fetal macrosomia, and postpartum hemorrhage in the group with treatment duration <4 weeks were significantly lower than those in the groups with 4-8 and >8 weeks treatment duration (P < 0.05). L-T4 treatment can significantly reduce the risks of adverse pregnancy outcomes in pregnant women with SCH. The shorter the treatment duration required to reach the target TSH level and the earlier the gestational week when the target TSH level is achieved through treatment, the lower the incidence of complications.


Assuntos
Hipotireoidismo/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Tiroxina/administração & dosagem , Adulto , Feminino , Idade Gestacional , Humanos , Gravidez , Complicações na Gravidez/prevenção & controle , Tiroxina/uso terapêutico , Resultado do Tratamento
7.
Zhonghua Yu Fang Yi Xue Za Zhi ; 50(5): 418-22, 2016 May.
Artigo em Chinês | MEDLINE | ID: mdl-27141897

RESUMO

OBJECTIVE: To investigate the effect of occupational toluene diisocyanate(TDI) exposure on matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-1(TIMP-1), and analysis of the correlation of MMP-9,TIMP-1,MMP-9/TIMP-1 and lung function. METHODS: In October 2014, based on cluster sampling, we conducted a cross-sectional study in a TDI production factory located in China's western region. 61 exposed workers were recruited from workers engaged in packing, operating and checking. Based on different levels of the external exposure, the packers were classified as high exposed group, while operators and checkers as low exposed group. 58 factory managers, matching age and agent, were selected as controls, having same work intense and not contacting the TDI or other allergens. The questionnaire surveys were used to obtain the agent, age, work age, smoking and drinking, personal and family allergic history, occupational history, and the recent health conditions. The levels of MMP-9 and TIMP-1 in serum of subjects were determind by ELISA. The time weighted average concentrations (8h-TWA) were used to describe the levels of TDI air exposure in working environment. Spearman correlation assay was used to investigate the correlation of MMP-9, TIMP-1, MMP-9/TIMP-1 and lung function, exposure time. RESULTS: 8-hour TWA means of TDI air levels in exposed group, packers, operators and checkers were 0.39, 0.76, 0.25 mg/m(3), respectively . According to the external exposure concentration, the packers were classified as high exposed group, and the operators and checkers were classified as low exposed group. In controls, low exposed group and high exposed group, the levels of MMP-9, respectively, were (807.21±347.70),(586.91±317.50),(388.94±312.01) ng/ml (χ(2)=16.69, P<0.001), respectively, and the P50(P25-P75) of MMP-9/TIMP-1 were 4.67(2.87-6.68), 2.3(1.44-3.48), 1.11(0.59-1.48) (χ(2)=39.42, P<0.001), respectively, and the concentrations of TIMP-1, were (173.44±72.67), (236.12±51.98), (302.81±44.39) ng/ml (F=20.09, P< 0.001), respectively. The levels P50(P25-P75) of FVC, FEV1.0 and FEV1.0/FVC in exposed group were, 92.8% (86.0%-101.8%), 85.5%(76.7%-92.8%), 112.5(108.2-118.5), respectively, which were lower than that in control group (124.3%(107.9%-144.2%), 142.7%(119.1%-155.7%), 129.2(123.5-134))(Z values were 7.70, 8.97, 8.62, and all P<0.001). Spearman rank correlation analysis showed that levels of MMP-9 were positively associated with FEV1.0, and FEV1.0/FVC (r values were 0.27, 0.25, respectively, all P<0.05), and The levels of TIMP-1 were negatively associated with FVC, FEV1.0, and FEV1.0/FVC (r valuse were -0.33, -0.39, -0.39, all P<0.05).The levels of MMP-9 were negatively correlated with exposure time(r=-0.26, P=0.040). The positive correlations of MMP-9/TIMP-1 with FVC, FEV1.0, and FEV1.0/FVC were also found (r valuse were 0.34, 0.44, 0.40, all P<0.05). CONCLUSION: TDI exposure could induce the downs of MMP-9 and MMP-9/TIMP-1 associated with lung functions. The MMP-9 and MMP-9/TIMP-1,in a way, could reflect the respiratory inflammatory injury caused by TDI exposure.


Assuntos
Metaloproteinase 9 da Matriz/metabolismo , Exposição Ocupacional/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Tolueno 2,4-Di-Isocianato/efeitos adversos , Adulto , Idoso , China , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/metabolismo , Pulmão/patologia , Ventilação Pulmonar , Fumar , Capacidade Vital
8.
J Wound Care ; 24(6 Suppl): S14-6, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26075510

RESUMO

Many medical devices, such as pulse oximetry, ventilation masks and other splints are put on critically ill patients. Although these devices are designed to deliver relatively low physical pressure to the skin of the patient, they can still cause pressure ulcers (PUs) in critically ill patients. There are reports of medical device-related PUs on the face. Here we describe forehead skin necrosis caused by the securing helmet for the Sengstaken-Blakemore tube. It is difficult to detect this kind of PU early, because most of the patients have decreased mental status or delirium due to varix bleeding. For this reason, medical staff should be aware of the risk of developing a PU by the device and take preventive measures accordingly.


Assuntos
Drenagem/instrumentação , Traumatismos Faciais/etiologia , Traumatismos Faciais/terapia , Testa/lesões , Dispositivos de Proteção da Cabeça/efeitos adversos , Úlcera por Pressão/etiologia , Úlcera por Pressão/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
9.
Methodist Debakey Cardiovasc J ; 18(3): 78-86, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35734158

RESUMO

During the first 2 years of the coronavirus-19 pandemic, many changes and innovations occurred to overcome the challenges associated with the pandemic and improve cardiovascular training. This review highlights the literature on the pandemic response regarding cardiovascular fellowship education and identifies areas of need to ensure future opportunities for fellows to achieve competency and career advancement. Specifically, we describe the recent changes to the four cornerstones of cardiovascular training: core content education, procedural training, career development, and the well-being of trainees.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/terapia , Educação Médica/normas , Educação Médica/tendências , Estudantes de Medicina/psicologia , Infecções por Coronavirus/epidemiologia , Bolsas de Estudo , Humanos , Pandemias
10.
Diabetes Care ; 45(3): 594-603, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35015860

RESUMO

OBJECTIVE: Health-related expenditures resulting from diabetes are rising in the U.S. Medication nonadherence is associated with worse health outcomes among adults with diabetes. We sought to examine the extent of reported cost-related medication nonadherence (CRN) in individuals with diabetes in the U.S. RESEARCH DESIGN AND METHODS: We studied adults age ≥18 years with self-reported diabetes from the National Health Interview Survey (NHIS) (2013-2018), a U.S. nationally representative survey. Adults reporting skipping doses, taking less medication, or delaying filling a prescription to save money in the past year were considered to have experienced CRN. The weighted prevalence of CRN was estimated overall and by age subgroups (<65 and ≥65 years). Logistic regression was used to identify sociodemographic characteristics independently associated with CRN. RESULTS: Of the 20,326 NHIS participants with diabetes, 17.6% (weighted 2.3 million) of those age <65 years reported CRN, compared with 6.9% (weighted 0.7 million) among those age ≥65 years. Financial hardship from medical bills, lack of insurance, low income, high comorbidity burden, and female sex were independently associated with CRN across age groups. Lack of insurance, duration of diabetes, current smoking, hypertension, and hypercholesterolemia were associated with higher odds of reporting CRN among the nonelderly but not among the elderly. Among the elderly, insulin use significantly increased the odds of reporting CRN (odds ratio 1.51; 95% CI 1.18, 1.92). CONCLUSIONS: In the U.S., one in six nonelderly and one in 14 elderly adults with diabetes reported CRN. Removing financial barriers to accessing medications may improve medication adherence among these patients, with the potential to improve their outcomes.


Assuntos
Diabetes Mellitus , Adesão à Medicação , Adolescente , Adulto , Idoso , Comorbidade , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Feminino , Gastos em Saúde , Humanos , Inquéritos e Questionários , Estados Unidos
11.
ASAIO J ; 66(6): 610-619, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31651460

RESUMO

Despite advances in left ventricular assist device (LVAD) technology, right ventricular failure (RVF) continues to be a complication after implantation. Most patients undergoing LVAD implantation have underlying right ventricular (RV) dysfunction (either as a result of prolonged LV failure or systemic disorders) that becomes decompensated post-implantation. Additional insults include intra-operative factors or a sudden increase in preload in the setting of increased cardiac output. The current literature estimates post-LVAD RVF from 3.9% to 53% using a diverse set of definitions. A few of the risk factors that have been identified include markers of cardiogenic shock (e.g., dependence on inotropes and Interagency Registry for Mechanically Assisted Circulatory Support profiles) as well as evidence of cardiorenal or cardiohepatic syndromes. Several studies have devised multivariable risk scores; however, their performance has been limited. A new functional assessment of RVF and a novel hepatic marker that describe cholestatic properties of congestive hepatopathy may provide additional predictive value. Furthermore, future studies can help better understand the relationship between pulmonary hypertension and post-LVAD RVF. To achieve our ultimate goal-to prevent and effectively manage RVF post-LVAD-we must start with a better understanding of the risk factors and pathophysiology. Future research on the different etiologies of RVF-ranging from acute post-surgical complication to late-onset RV cardiomyopathy-will help standardize definitions and tailor therapies appropriately.


Assuntos
Coração Auxiliar/efeitos adversos , Disfunção Ventricular Direita/epidemiologia , Disfunção Ventricular Direita/etiologia , Feminino , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Disfunção Ventricular Direita/fisiopatologia
12.
Curr Mol Med ; 18(5): 273-286, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30289073

RESUMO

BACKGROUND: Whereas retinal pigment epithelial (RPE) cells are known to secrete VEGF-A and VEGFR2, the functions of the autocrine VEGF signaling remain unclear. Meanwhile, anti-VEGF therapies have been applied routinely to treat ocular vascular diseases. OBJECTIVE: The aim of this study was to determine the functions of the VEGF signaling in RPE cells and evaluate the consequences of its interruption. METHODS: The genes involved in the VEGF and Hippo signal pathways were knocked down with siRNAs in both ARPE-19 cell line and human primary RPE cells via transient transfection whereas overexpression of VEGFR2 was mediated via adenovirus transduction. Expression of the epithelial-mesenchymal transition (EMT) markers and the downstream genes of YAP were determined by real-time PCR and Western Blot analysis. Immunofluorescence staining was utilized to determine gene expression in tissue and mouse samples. RESULTS: Knockdown of VEGFR2 results in epithelial-mesenchymal transition in vitro and in vivo. Overexpression of VEGFR2 suppresses TGF ß-mediated EMT in RPE cells. Loss of VEGF-C rather than VEGF-A induces EMT. Mechanistically, the VEGFR2 ablation-induced EMT in RPE cells is mediated by activation of YAP, an effector of the Hippo pathway. Finally, the immunohistochemical analysis of VEGFR2 and YAP in human proliferative vitreoretinopathy (PVR) membranes indicates a tendency of an inverse correlation between VEGFR2-positive and YAP-positive cells. CONCLUSIONS: Our results disclose unexpected novel roles of VEGFR2 and VEGF-C in the process of EMT of RPE cells and in the Hippo pathway. The data shown here demonstrated that VEGFR2 and VEGF-C are important to maintain the normal physiological state of RPE cells.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transição Epitelial-Mesenquimal , Regulação da Expressão Gênica , Fosfoproteínas/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Transdução de Sinais , Fator C de Crescimento do Endotélio Vascular/biossíntese , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/genética , Linhagem Celular , Técnicas de Silenciamento de Genes , Humanos , Fosfoproteínas/genética , Epitélio Pigmentado da Retina/citologia , Fatores de Transcrição , Fator C de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Proteínas de Sinalização YAP
13.
Curr Mol Med ; 17(4): 304-311, 2017 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-29110610

RESUMO

BACKGROUND: Macrophages undergo polarization or activation in response to environmental stimuli, an essential process for proper immune response. Meanwhile, excessive activation of macrophages causes autoimmune diseases. It is therefore crucial to prevent over-activation of macrophage in order to maintain the proper immune response. Arginase 1 (Arg-1) plays a critical role in coordinating the immune response by regulating availability of arginine. OBJECTIVE: To understand the mechanism of Arg-1 regulation. METHODS: Real-time PCR and Western Blot analysis were utilized to examine the Arg-1 levels expressed from the VEGFR1-deleted and VEGFR1-TK-deficient bone marrowderived macrophages (BMDMs). RESULTS: The VEGFR1-mediated signaling suppressed IL-4-induced Arg-1 expression. Deletion of VEGFR1 resulted in elevated Arg-1 expression and the tyrosine kinase domain of VEGFR1 was required for the suppression. Each of three ligands of VEGFR1, VEGF-A, VEGF-B and PIGF, mediated the inhibition to the similar degree. CONCLUSION: Our findings identified a novel function of the VEGFR1 signaling in avoiding over-expression of Arginase 1 potentially to maintain the proper innate immune response.


Assuntos
Arginase/imunologia , Regulação Enzimológica da Expressão Gênica/imunologia , Interleucina-4/imunologia , Macrófagos/metabolismo , Transdução de Sinais/imunologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/imunologia , Animais , Arginase/genética , Deleção de Genes , Imunidade Inata , Interleucina-4/genética , Macrófagos/citologia , Camundongos , Camundongos Transgênicos , Transdução de Sinais/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética
15.
Semin Hematol ; 35(3 Suppl 4): 32-8, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9779880

RESUMO

The standard treatment of multiple myeloma is systemic chemotherapy. Despite 30 years of drug development in myeloma, there are no new drug regimens significantly superior to melphalan and prednisone. In addition, phase II studies of new drugs in myeloma have been disappointing, with low response rates and no prolongation in survival. The topoisomerase I (topo I) inhibitors are a new class of anticancer agents with a wide spectrum of activity in human malignancies. Recent evaluation of the topo I inhibitor topotecan demonstrated activity in advanced myeloma, suggesting a possible role for these drugs in the treatment of this disease. Further evaluation of the mechanisms of resistance to topo I inhibitors, study of combination therapy with topotecan, and evaluation of other topo I poisons in multiple myeloma is proposed.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Inibidores da Topoisomerase I , Ensaios Clínicos Fase II como Assunto , Humanos
16.
Prog Brain Res ; 135: 215-9, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12143342

RESUMO

There have been suggestions that seizures in some way modify brain function and that each seizure increases the risk for further seizures. Reports thus far on this phenomenon have been flawed because of inappropriate study design. We have evaluated the risk for seizure recurrence following a first unprovoked seizure in a cohort identified at their first unprovoked seizure. Individuals with low risk for a seizure recurrence demonstrate a significant increase in risk for seizure recurrence with increasing numbers of seizures. This is the first time that a progressive increase in risk for seizures with increasing number of seizures has been demonstrated in humans. Since the majority of these cases will ultimately go into remission and discontinue antiseizure medication, there must be competing forces that increase seizure risk and promote seizure suppression. We need appropriate animal models to better understand both processes and their interactions.


Assuntos
Convulsões/fisiopatologia , Seguimentos , Humanos , Recidiva , Fatores de Risco , Convulsões/epidemiologia , Convulsões/etiologia
17.
Toxicol Lett ; 121(2): 119-26, 2001 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-11325562

RESUMO

It has been demonstrated previously that sodium azide reduces the clastogenicity of several DNA topoisomerase II (topo II) poisons in cultured mammalian cells. These studies suggested that azide may be a catalytic topo II inhibitor. Azide interferes with mitochondrial production of ATP and is also known to inhibit cellular ATPases. Since topo II requires ATP for catalytic activity (enzyme turnover), it seemed likely that interference with ATP levels or ATP catabolism was the underlying mechanism of topo II inactivation; however, this has not been examined in living cells under conditions where the endogenous topo II is active on genomic DNA. The present studies were carried out to verify that azide inhibits endogenous topo II in cells. We show that azide blocks both decatenation and relaxation activity of purified topo II in a concentration dependent manner and reduces topoII/DNA covalent complex formation in cells. From these studies, it is concluded that sodium azide catalytically inactivates topo II via an ATP-sensitive process.


Assuntos
DNA Topoisomerases Tipo II , Isoenzimas/antagonistas & inibidores , Azida Sódica/farmacologia , Inibidores da Topoisomerase II , Antígenos de Neoplasias , Antineoplásicos Fitogênicos , Catálise/efeitos dos fármacos , Dano ao DNA , DNA Topoisomerases Tipo II/química , Proteínas de Ligação a DNA , Relação Dose-Resposta a Droga , Etoposídeo , Células HeLa , Humanos , Isoenzimas/química
18.
J Pharm Sci ; 84(12): 1455-63, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8748329

RESUMO

Two scaling laws for predicting polymer and drug release profiles from hydrophilic matrices were developed. They were developed on the basis of the diffusion layer and the polymer disentanglement concentration, rho p,dis, the critical polymer concentration below which polymer chains detach off a gelled matrix that is undergoing simultaneous swelling and dissolution. The relation between rho p,dis and molecular weight, M1 for (hydroxypropyl)methylcellulose (HPMC) in water was established as rho p,dis (g/mL) varies M-0.8. This power-law relationship for rho p,dis, along with the diffusion layer adjacent to the gelled matrix, leads to the scaling law of mp(t)/mp(infinity) varies Meq-1.15, where mp(t)/mp(infinity) is the fractional HPMC release. The scaling law explains the observation that polymer and drug release rates decreased sharply with M at low M and approach limiting values at high M. Experimentally, mp(t)/mp(infinity) was found to scale with Meq as mp(t)/mp(infinity) varies Meq-0.93, where Meq is the equivalent matrix molecular weight. Moreover, fractional drug release, md(t)/md(infinity), followed Meq as md(t)/md(infinity) varies Meq-0.48. These two scaling laws imply that, if the release profiles are known for one composition, release profiles for other compositions can be predicted. The above two power laws lead to two master curves for mp(t)/mp(infinity) and md(t)/md(infinity), suggesting that the release mechanism for soluble drugs from HPMC matrices is independent of matrix compositions, presumably via a diffusion-controlled process. Limitations of the power laws are discussed.


Assuntos
Benzodiazepinas/química , Preparações de Ação Retardada/química , Metilcelulose/análogos & derivados , Química Farmacêutica , Derivados da Hipromelose , Metilcelulose/química , Modelos Químicos , Peso Molecular , Solubilidade , Comprimidos/química , Teofilina/química
19.
J Pharm Sci ; 86(11): 1293-8, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9383743

RESUMO

A semiempirical formula was developed for the diffusion coefficient, Dp, of polymer within the diffusion layer adjacent to a matrix undergoing swelling and dissolution. This formula of Dp was a key element in a comprehensive mathematical model that described the swelling and dissolution of polymer and the release of drug. For hydroxypropyl methylcellulose (HPMC), Dp can be related to molecular weight (M) and concentration (Cp) of HPMC as Dp approximately 7.24 x 10(-5) M-0.6 [1+ 700(M/ 96000)0.7Cp/8]-2. Consistent with literature results, this formula yields Dp infinity M-0.64 under a dilute condition and Dp infinity Cp-7/4M-2 under a semidilute condition. Accordingly, the average Dp within the diffusion layer, was determined as infinity M-0.53, suggesting that the average mobility of HPMC within the diffusion layer decreases with M. This scaling law, combined with the relationship of Cp.dis infinity M-0.8, led to an important scaling law for matrix dissolution flux, Jp infinity M-1.15. The parameter Cp.dis, defined as the polymer disentanglement concentration or the polymer concentration at the tablet-diffusion layer interface, was a key parameter in that mathematical-model. The scaling law of Jp infinity M-1.15 indicates that the matrix dissolution rate decrease sharply with M at low M and gradually approaches a plateau as M becomes large. The plateau characteristics of Jp with M is consistent with the limiting drug release rate observed for HPMC-containing matrices, suggesting the critical role matrix dissolution plays in drug release.


Assuntos
Lactose/análogos & derivados , Metilcelulose/análogos & derivados , Difusão , Lactose/química , Metilcelulose/química , Oxazinas , Solubilidade
20.
J Pharm Sci ; 84(12): 1464-77, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8748330

RESUMO

A comprehensive model is developed to describe the swelling/dissolution behaviors and drug release from hydrophilic matrices. The major thrust of this model is to employ an important physical property of the polymer, the polymer disentanglement concentration, rho p,dis, the polymer concentration below which polymer chains detach off the gelled matrix. For (hydroxypropyl)methylcellulose (HPMC) in water, we estimate that rho p,dis scales with HPMC molecular weight, M, as rho p,dis varies M-0.8. Further, matrix dissolution is considered similar to the dissolution of an object immersed in a fluid. As a result, a diffusion layer separating the matrix from the bulk solution is incorporated into the transport regime. An anisotropic expansion model is also introduced to account for the anisotropic expansion of the matrix where surface area in the radial direction dominates over the axial surface area. The model predicts that the overall tablet size and the characteristic swelling time correlate with rho p,dis qualitatively. Two scaling laws are established for fractional polymer (mp(t)/mp(infinity)) and drug (md(t)/md(infinity)) released as mp(t)/mp(infinity) varies M-1.05 and md(t)/md(infinity) varies M-0.24, consistent with the limiting polymer molecular weight effect on drug release. Model predictions for polymer and drug release agree well with observations, within 15% error. Evolution of water concentration profiles and the detailed structure of a swollen matrix are discussed.


Assuntos
Benzodiazepinas/química , Preparações de Ação Retardada/química , Metilcelulose/análogos & derivados , Química Farmacêutica , Derivados da Hipromelose , Matemática , Metilcelulose/química , Modelos Químicos , Peso Molecular
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