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1.
AJNR Am J Neuroradiol ; 44(4): 417-423, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36927761

RESUMO

BACKGROUND AND PURPOSE: Incidental findings are discovered in neuroimaging research, ranging from trivial to life-threatening. We describe the prevalence and characteristics of incidental findings from 16,400 research brain MRIs, comparing spontaneous detection by nonradiology scanning staff versus formal neuroradiologist interpretation. MATERIALS AND METHODS: We prospectively collected 16,400 brain MRIs (7782 males, 8618 females; younger than 1 to 94 years of age; median age, 38 years) under an institutional review board directive intended to identify clinically relevant incidental findings. The study population included 13,150 presumed healthy volunteers and 3250 individuals with known neurologic diagnoses. Scanning staff were asked to flag concerning imaging findings seen during the scan session, and neuroradiologists produced structured reports after reviewing every scan. RESULTS: Neuroradiologists reported 13,593/16,400 (83%) scans as having normal findings, 2193/16,400 (13.3%) with abnormal findings without follow-up recommended, and 614/16,400 (3.7%) with "abnormal findings with follow-up recommended." The most common abnormalities prompting follow-up were vascular (263/614, 43%), neoplastic (130/614, 21%), and congenital (92/614, 15%). Volunteers older than 65 years of age were significantly more likely to have scans with abnormal findings (P < .001); however, among all volunteers with incidental findings, those younger than 65 years of age were more likely to be recommended for follow-up. Nonradiologists flagged <1% of MRIs containing at least 1 abnormality reported by the neuroradiologists to be concerning enough to warrant further evaluation. CONCLUSIONS: Four percent of individuals who undergo research brain MRIs have an incidental, potentially clinically significant finding. Routine neuroradiologist review of all scans yields a much higher rate of significant lesion detection than selective referral from nonradiologists who perform the examinations. Workflow and scan review processes need to be carefully considered when designing research protocols.


Assuntos
Encefalopatias , Encéfalo , Masculino , Feminino , Humanos , Adulto , Encéfalo/patologia , Encefalopatias/diagnóstico por imagem , Encefalopatias/epidemiologia , Achados Incidentais , Imageamento por Ressonância Magnética , Neuroimagem , Voluntários
2.
Climacteric ; 19(1): 49-59, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26652904

RESUMO

BACKGROUND: Serotonin (5-hydroxytryptamine, 5-HT) is modulated by sex steroid hormones and affects vascular function and mood. In the Kronos Early Estrogen Prevention Cognitive and Affective Ancillary Study (KEEPS-Cog), women randomized to oral conjugated equine estrogens (oCEE) showed greater benefit on affective mood states than women randomized to transdermal 17ß-estradiol (tE2) or placebo (PL). This study examined the effect of these treatments on the platelet content of 5-HT as a surrogate measure of 5-HT synthesis and uptake in the brain. METHODS: The following were measured in a subset (n = 79) of women enrolled in KEEPS-Cog: 5-HT by ELISA, carotid intima-medial thickness (CIMT) by ultrasound, endothelial function by reactive hyperemic index (RHI), and self-reported symptoms of affective mood states by the Profile of Mood States (POMS) questionnaire. RESULTS: Mean platelet content of 5-HT increased by 107.0%, 84.5% and 39.8%, in tE2, oCEE and PL groups, respectively. Platelet 5-HT positively correlated with estrone in the oCEE group and with 17ß- estradiol in the tE2 group. Platelet 5-HT showed a positive association with RHI, but not CIMT, in the PL and oCEE groups. Reduction in mood scores for depression-dejection and anger-hostility was associated with elevations in platelet 5-HT only in the oCEE group (r = -0.5, p = 0.02). CONCLUSIONS: Effects of oCEE compared to tE2 on RHI and mood may be related to mechanisms involving platelet, and perhaps neuronal, uptake and release of 5-HT and reflect conversion of estrone to bioavailable 17ß-estradiol in platelets and the brain.


Assuntos
Afeto/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios , Estrogênios Conjugados (USP)/administração & dosagem , Serotonina/sangue , Administração Cutânea , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa
3.
Indian J Pharm Sci ; 77(4): 439-45, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26664060

RESUMO

Pueraria tuberosa is known for its therapeutic potentials in cardiovascular disorders, but its effect in angiogenesis has not been studied so far. In this study, a computational approach has been applied to elucidate the role of the phytochemicals in inhibition of angiogenesis through modulation of vascular endothelial growth factor receptors: Vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2, major factors responsible for angiogenesis. Metabolite structures retrieved from PubChem and KNApSAcK - 3D databases, were docked using AutoDock4.2 tool. Hydrogen bond and molecular docking, absorption, distribution, metabolism and excretion and toxicity predictions were carried out using UCSF Chimera, LigPlot(+) and PreADMET server, respectively. From the docking analysis, it was observed that puerarone and tuberostan had significant binding affinity for the intracellular kinase domain of vascular endothelial growth factor receptors-1 and vascular endothelial growth factor receptor-2 respectively. It is important to mention that both the phytochemicals shared similar interaction profile as that of standard inhibitors of vascular endothelial growth factor receptors. Also, both puerarone and tuberostan interacted with Lys861/Lys868 (adenosine 5'-triphosphate binding site of vascular endothelial growth factor receptors-1/vascular endothelial growth factor receptors-2), thus providing a clue that they may enforce their inhibitory effect by blocking the adenosine 5'-triphosphate binding domain of vascular endothelial growth factor receptors. Moreover, these molecules exhibited good drug-likeness, absorption, distribution, metabolism and excretion properties without any carcinogenic and toxic effects. The interaction pattern of the puerarone and tuberostan may provide a hint for a novel drug design for vascular endothelial growth factor tyrosine kinase receptors with better specificity to treat angiogenic disorders.

4.
J Endocrinol Invest ; 38(4): 455-61, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25430996

RESUMO

PURPOSE: To determine the dose-dependent effects of testosterone administration on cognition in women with low testosterone levels. METHODS: 71 hysterectomized women with or without oophorectomy with total testosterone <31 ng/dl and/or free testosterone <3.5 pg/ml received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly intramuscular injections of placebo, 3, 6.25, 12.5, or 25 mg testosterone enanthate for 24 weeks. Total testosterone was measured in serum by LC-MS/MS, and free testosterone levels were measured by equilibrium dialysis. Cognitive function was evaluated using a comprehensive battery of standardized neuropsychological tests at baseline and 24 weeks. RESULTS: 46 women who had baseline and end-of-treatment cognitive function data constituted the analytic sample. The five groups were similar at baseline. Mean on-treatment nadir total testosterone concentrations were 15, 89, 98, 134, and 234 ng/dl in the placebo, 3, 6.25, 12.5, and 25 mg groups, respectively. No significant changes in spatial ability, verbal fluency, verbal memory, or executive function were observed in any treatment arm compared to placebo even after adjustment for baseline cognitive function, age, and education. Multiple regression analysis did not show any significant relation between changes in testosterone concentrations and change in cognitive function scores. CONCLUSION: Short-term testosterone administration over a wide range of doses for 24 weeks in women with low testosterone levels was neither associated with improvements nor worsening of cognitive function.


Assuntos
Cognição/efeitos dos fármacos , Função Executiva/efeitos dos fármacos , Histerectomia , Testosterona/metabolismo , Testosterona/farmacologia , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Estradiol/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Ovariectomia , Testosterona/administração & dosagem , Resultado do Tratamento
5.
Eur J Obstet Gynecol Reprod Biol ; 181: 233-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25171269

RESUMO

OBJECTIVE: To compare viral load on careHPV DNA testing in self-collected vaginal (VHPC) and clinician-collected cervical (CHPC) samples for the detection of high-grade cervical intra-epithelial neoplasia (CIN). STUDY DESIGN: Cross-sectional study. Ever-married women aged 30-59 years were targeted for cervical screening. On attendance for screening, vaginal self-sampling was performed by the woman, and an auxiliary nurse midwife subsequently performed a per-speculum examination, collected a CHPV sample and a Pap smear, and made a visual inspection of the cervix with acetic acid. The ratio of viral load expressed in relative light units to positive controls set at a cut-off of 1pg/ml was used for careHPV quantitative assessment. The median viral load was compared using non-parametric tests. Receiver operating characteristic (ROC) curves were constructed for the detection of CINII+ and CINIII+ in CHPV and VHPV samples. RESULTS: Overall, the median viral load in the 4658 women screened was higher in CHPV samples compared with VHPV samples (9.8-fold higher in cases of high-grade CIN). The median viral load was significantly higher among Pap-positive women compared with Pap-negative women in both CHPV and VHPV samples (p<0.01). Assessment by ROC analysis for the detection of high-grade CIN did not differ significantly between CHPV and VHPV samples. CONCLUSION: Viral load on careHPV testing was comparable between self- and clinician-collected samples for the detection of high-grade CIN. The self-sampling approach may be an option for screening in low-resource countries.


Assuntos
Colo do Útero/virologia , DNA Viral/análise , Manejo de Espécimes/métodos , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Vagina/virologia , Adulto , Estudos Transversais , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Índia , Pessoa de Meia-Idade , Papillomaviridae/genética , Curva ROC , População Rural , Autocuidado , Neoplasias do Colo do Útero/virologia , Carga Viral , Displasia do Colo do Útero/virologia
6.
Indian J Cancer ; 51(2): 124-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25104192

RESUMO

CONTEXT: Pap smear testing as a conventional cervical screening approach has limitations for implementation and aided visual cervical testing has varying results in different regions. AIMS: The aim of this study is to demonstrate the performance of aided visual cervical screening tests as against conventional Pap smear testing in a rural community setting of North India. SETTINGS AND DESIGN: This was a rural community based cross-sectional study. MATERIALS AND METHODS: All 7603 ever married women of age 30-59 years surveyed in a pocket of Dadri Tehsil, Uttar Pradesh, India were targeted for screening by Pap, visual inspection of cervix using acetic acid (VIA) and visual inspection of cervix using Lugol's iodine (VILI) methods. Screen positives were referred to colposcopy and confirmation by histology. STATISTICAL ANALYSIS USED: Detection of histological cervical intraepithelial neoplasia (CIN) II + and CIN III + assessed separately by sensitivity, specificity and likelihood ratio's and predictive values. Analysis of data was performed by using IBM SPSS statstics software version 16.0. RESULTS: A total of 65.6%(4988/7604) eligible women of 30-59 years age group in the target population were screened. Out of 4988, further analysis was performed on 4148 after excluding those who did not complete all screenings, who lost to follow-up and had missing histology results. Screen positivity rates by Pap (ASCUS and above), VIA and VILI were 2.6%, 9.7% and 13.5% respectively. Sensitivity and specificity of detecting the CIN III+ lesions were 87.5 and 98.8% for Pap, 50.0% and 96.7% for VIA and 50.0% and 95.7% for VILI respectively. CONCLUSIONS: VIA screening demonstrated as a feasible primary screening test for detecting high grade CIN and as to perform better when the Pap test is not feasible.


Assuntos
Detecção Precoce de Câncer/métodos , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Ácido Acético , Adulto , Estudos Transversais , Feminino , Humanos , Índia , Iodetos , Pessoa de Meia-Idade , População Rural , Sensibilidade e Especificidade , Esfregaço Vaginal
7.
Eur J Obstet Gynecol Reprod Biol ; 176: 75-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24685404

RESUMO

OBJECTIVE: To compare cervical careHPV screening in a rural community setting with other methods of cervical screening for the detection of high-grade cervical intra-epithelial neoplasia (CIN). STUDY DESIGN: Cross-sectional study. All ever-married women aged 30-59 years surveyed in an administrative area of Uttar Pradesh, India were targeted for screening by careHPV (cervical and vaginal samples), Pap test and visual inspection of the cervix following application of acetic acid (VIA). Women who screened positive were referred for colposcopy and the results were confirmed histologically. Sensitivity, specificity and predictive values for the detection of histological CINII+ and CINIII+ were assessed for each screening test. RESULTS: Sixty-five percent (5032/7704) of the women invited for cervical screening agreed to participate in the study. Screen-positive rates for cervical careHPV, vaginal careHPV, Pap test and VIA were 3%, 2%, 3% and 6%, respectively. Data for women who did not complete all screening modes, women lost to follow-up and women with missing histological results were excluded before data analysis, resulting in a final sample size of 4658. Cervical careHPV had high sensitivity (85%) for the detection of CINIII+ lesions and moderate sensitivity (53%) for the detection of CINII+ lesions. Sensitivities for the detection of CINIII+ and CINII+ were 54% and 41% for vaginal careHPV, 62% and 44% for Pap test, and 8% and 22% for VIA, respectively. CONCLUSION: Cervical careHPV testing is superior to VIA and Pap test for the detection of high-grade CIN in a rural community setting.


Assuntos
Testes de DNA para Papilomavírus Humano/métodos , Programas de Rastreamento/métodos , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Ácido Acético , Adulto , Colposcopia , Estudos Transversais , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Índia/epidemiologia , Pessoa de Meia-Idade , Teste de Papanicolaou , Valor Preditivo dos Testes , População Rural , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/epidemiologia , Displasia do Colo do Útero/epidemiologia
8.
J Biomed Nanotechnol ; 9(5): 915-25, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23802424

RESUMO

Gemcitabine (dFdC) mediated cancer treatment faces obstacles, due to its high hydrophilicity. A valuable strategy was executed by synthesizing lipophilic fatty acid derivative of dFdC i.e., 4-(N)-stearoyl gemcitabine (C18dFdC), built-in into polymeric poly-lactic-co-glycolic acid nanoparticles (PLGA NPs) and compared with that of parent drug. Encapsulation of derivative within NPs was higher (68.24 +/- 3.64%) than dFdC and showed comparatively sustained drug release (19.87 +/- 1.73% within 12 hours), with a proof of increased biological half life. The cytotoxicity and flow cytometric analysis displayed enhanced MCF-7 cell inhibition by C18dFdC-NPs with higher uptake compared to dFdC-NPs. Interestingly, like gemcitabine, C18dFdC-NPs did not induce appreciable differences in blood parameters and in vivo tissue toxicity study demonstrating safe use of derivative at 40 mg/kg dose. In conclusion, the preclinical data obtained in vitro and in vivo demonstrate the C18dFdC-nanocarrier as an advantageous and promising delivery system for cancer treatment along with the potential to improve the clinical outcome of gemcitabine chemotherapy.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/análogos & derivados , Sistemas de Liberação de Medicamentos , Nanopartículas , Neoplasias/tratamento farmacológico , Pró-Fármacos/administração & dosagem , Animais , Linhagem Celular Tumoral , Desoxicitidina/administração & dosagem , Ácidos Graxos/administração & dosagem , Ácidos Graxos/química , Feminino , Humanos , Masculino , Camundongos , Pró-Fármacos/química , Ratos , Ratos Wistar , Gencitabina
9.
Indian J Med Paediatr Oncol ; 30(2): 71-5, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20596306

RESUMO

BACKGROUND: The uterine cervix is the second most common site of cancer among Indian women.Though the human papillomavirus has been demonstrated to be a causative agent for this cancer, a variety of other risk factors are in play, such as sexual and reproductive patterns, socioeconomic, hygienic practices, and diet. The accumulated evidence suggests that cervical cancer is preventable and is highly suitable for primary prevention. The dietary intake of antioxidants and vitamins like vitamin A, carotenoids, vitamin C, folacin and tocopherol is found to have protective effects against cancer of the cervix. Dietary data regarding cervical cancer are still scanty. OBJECTIVE: The present study was therefore undertaken to study the dietary pattern among uterine cervical cancer patients and normal controls. MATERIALS AND METHODS: A total of 60 consecutive patients and 60 controls were enrolled from a referral hospital during the year 2004. A schedule inclusive of the food frequency pattern and 24-h dietary recall along with the general information was administered to all the enrolled subjects to describe findings on the food consumption pattern along with other important factors. RESULTS: The mean intake of energy, protein, vitamins, etc., between the cases and controls was not significantly different except for the vitamin C level. Serum vitamin E was found to have lower average in patients as compared to controls. The nutrient intake of cervical cancer patients and controls was grossly deficient in the socioeconomic group studied. With regard to the macronutrient intake, calorie and protein intakes showed a deficit of around 50% when compared to RDA. CONCLUSION: The food consumption profile was not significantly different between cervical cancer patients and normal controls.

10.
Eur J Surg Oncol ; 34(7): 787-94, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18036765

RESUMO

AIM: To review the experience with hilar cholangiocarcinoma and to determine the results of a radical surgical approach in a UK centre. METHODS: A 10-year review of all patients treated surgically for proximal bile duct carcinoma at a single surgical unit was conducted. Patient demographics, disease details and histopathology reports were reviewed. From January 1993 through December 2003, 106 patients were admitted with the diagnosis of hilar cholangiocarcinoma and 61 patients received surgical exploration. RESULTS: Tumours were staged as follows (UICC 6th edition): stage IB, n=10 IIA, n=9; IIB, n=20; III, n=8; IV, n=14. Out of 61 patients, 44 had a resection (3 bile duct resection alone, 41 liver resection with bile duct resection), 5 were considered unresectable and 12 underwent liver transplantation (LT). The caudate lobe was excised in 34 of the patients and regional lymphadenectomy was systematically carried out. Para-aortic lymphadenectomy was performed in 17 cases. Portal vein resection was needed in 17 and hepatic artery resection was performed in 4 cases. Negative histologic margins (R0) were achieved in 20 patients and microscopic margin involvement (R1) was seen in 16. In the remaining 8 resected patients, localised metastasis were found (peritoneal deposits in 2, liver metastasis in 4 and positive para-aortic lymph nodes in 2); nevertheless the resection was performed and it was considered R2. Overall survival at 3 and 5 years for patients who underwent a resection was 43% and 28% including postoperative deaths. The 1-, 3- and 5-year actuarial survival rates for patients who underwent R0 resection were 78%, 64% and 45% respectively, including the postoperative deaths (n=3). The median survival time was 41.1 months. The 1-, 3- and 5-year actuarial survival rates for R1 resection and R2 were 60%, 26%, 26% and 25% and 0% respectively, while the median survival time for these groups was 15.4 and 6.8 months respectively. The actuarial survival rate at 1, 3 and 5 years for well-differentiated tumours (G1) was 73%, 54% and 40% (median 39.7 months). The figures for G2 were 60%, 48% and 0%. The figures for G3 (poorly differentiated) were 16% and 0% at three years (p=0.03).The overall survival at 3 and 5 years for those patients who had a liver transplant was 41% and 20% including early postoperative mortality. The tumour grading (presence of poorly differentiated tumour) was found to be the only independent factor affecting the survival time producing a hazard ratio of 4.3 (p=0.0034, 95% confidence interval 0.1007-6.342). CONCLUSIONS: Radical surgical resection is the best treatment for hilar cholangiocarcinoma. R0 resection provides acceptable 5-year survival, but R1 resection may also provide acceptable palliation. In our experience TNM stage and tumour grade were the main determinants of long-term survival.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Hepatectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos , Funções Verossimilhança , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Seleção de Pacientes , Assistência Perioperatória , Complicações Pós-Operatórias , Estudos Retrospectivos , Análise de Sobrevida , Reino Unido
11.
Eur J Vasc Endovasc Surg ; 33(6): 703-7, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17275360

RESUMO

OBJECTIVES: Cardiovascular mortality in patients with chronic critical lower limb ischaemia (CCLI) is high and early risk stratification in these patients may aid clinical management improving outcomes. Cardiac troponin I (cTnI) has prognostic significance in patients with unstable angina. The aim of this study was to evaluate the prognostic significance of cardiac troponins in CCLI patients who had no clinical evidence of unstable coronary heart disease. METHODS: Patients (n=152) admitted with CCLI to a single vascular unit over a two-year period were included prospectively in this study. Patients with clinical evidence of unstable coronary disease were excluded from the study. Patient demographics, clinical history, co-morbidity and risk factors for peripheral vascular disease were documented. Admission cTnI levels were recorded using a threshold, 0.1 ng/ml. The primary endpoint was mortality. RESULTS: Fifty-two patients (34.2%) had an elevated cTnI, whilst 100 (65.8%) had cTnI <0.1 ng/ml. Sixty-two patients died during the follow-up period, 38 with an elevated admission cTnI. Death rate in patients with cTnI >0.1 ng/nl was 73% compared with 24% in those with levels below the threshold (p<0.0001). Patients with elevated cTnI were significantly older than those with normal level (median age 76 years vs 71 years, p<0.001). An elevated cTnI was found to independently predict disease-specific mortality on Cox regression analysis (Hazard Ratio 4.2; 95% Confidence Interval 1.3-12.7). CONCLUSION: In this series of patients with CCLI the measurement of cTnI on admission was a significant independent predictor of survival. cTnI has potential as a prognostic test to stratify patients with a high cardiovascular risk and may enable further optimisation of these high-risk patients.


Assuntos
Isquemia/sangue , Perna (Membro)/irrigação sanguínea , Troponina I/sangue , Idoso , Idoso de 80 Anos ou mais , Angina Instável/sangue , Angina Instável/complicações , Angina Instável/mortalidade , Biomarcadores/sangue , Doença Crônica , Intervalos de Confiança , Feminino , Seguimentos , Humanos , Isquemia/complicações , Isquemia/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida
12.
J Hazard Mater ; 143(1-2): 192-7, 2007 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-17097226

RESUMO

This paper reports the synthesis of three new derivatives of 2,4,5-trinitroimidazole namely, 1-methyl-2,4,5-trinitroimidazole (III), 1-carboethoxy-2,4,5-trinitroimidazole (V) and 1-picryl-2,4,5-trinitroimidazole (VII). The title compounds (III) and (V) were synthesized by the nitration of 1-methyl-/1-carboethoxy-(2,4,5-triiodoimidazole) (II and IV) with fuming nitric acid at 0 degrees C and (VII) was synthesized by condensation of 2,4,5-triiodoimidazole (I) with picryl chloride to obtain 1-picryl-2,4,5-triiodoimidazole (VI) followed by its nitration with fuming nitric acid at 0 degrees C. The synthesized compounds have been characterized by elemental analysis, spectral and thermal techniques. The thermolysis studies using TG-DTA revealed exothermic decomposition of the nitroimidazoles (III, V and VII) with T(max) in the temperature range of 196-225 degrees C. The energy of activation obtained for these compounds was in the range 150-170 kJ/mol. The sensitivity data obtained for the newly synthesized compounds (III, V and VII) indicated their safe nature towards external stimuli (h(50%)>100 cm; friction>36 kg) and could be potential candidates for low vulnerable applications in the futuristic systems. The theoretically predicted performance parameters suggest that 1-methyl-2,4,5-trinitroimidazole (III), exhibits higher velocity of detonation (VOD: 8.8 km/s) compared to compounds V and VII (VOD: 7.6 and 8.41 km/s, respectively).


Assuntos
Imidazóis/síntese química , Nitrocompostos/síntese química , Nitroimidazóis/síntese química , Varredura Diferencial de Calorimetria , Transferência de Energia , Nitroimidazóis/química , Espectroscopia de Infravermelho com Transformada de Fourier
13.
Eur J Vasc Endovasc Surg ; 33(4): 391-4; discussion 395-6, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17164089

RESUMO

OBJECTIVES: Previous literature has suggested an association between AAA and the presence of elevated plasma homocysteine levels (HCY). Homocysteine can stimulate elastolysis in the arterial media via activation of elastase and matrix metalloproteinases. No evidence in the literature exists correlating aneurysm expansion and HCY. The study objective is to identify whether the rate of AAA expansion is related to HCY. METHODS: 108 patients undergoing surveillance for AAA were identified at our vascular surgical unit. AAA size and growth rate were assessed by serial ultrasonographic measurements. Fasting total HCY levels were measured using fluorescence polarisation immunoassays. Demographic details and atherosclerotic risk factors were noted all AAA patients. A multivariate analysis was performed for growth rate vs. HCY, hypertension and hypercholesterolaemia. The correlation between AAA growth rate, AAA size and HCY levels were calculated. RESULTS: 60% of patients with AAA had some degree of hyperhomocysteinaemia (> 15 micromol/l). Multivariate analysis showed HCY to be the only significant factor affecting AAA growth rate. A positive correlation was demonstrated between HCY levels and AAA growth rate using a linear regression model (R=0.28, p=0.003). Median growth rate among patients with hyperHCY was double that of patients with normal HCY (0.5 mm/month vs. 0.25 mm/month, p=0.003). A growth rate of > 10 mm/year was seen in 25% of hyper HCY patients and in only 2% of patients with normal HCY. In addition patients with hyper HCY and larger AAAs (> 4 cm) had a growth rate twice as fast as patients with hyper HCY and AAAs < 4 cm. CONCLUSIONS: A correlation between HCY and growth rate exists, although this is weak due to the multifactorial aetiology of AAAs. HyperHCY patients have faster expansion rates than patients with normal HCY, with significant numbers demonstrating rapid expansion (> 10 mm/year) and therefore an increased risk of rupture.


Assuntos
Aneurisma da Aorta Abdominal/patologia , Ruptura Aórtica/patologia , Homocisteína/sangue , Hiper-Homocisteinemia/complicações , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/etiologia , Ruptura Aórtica/sangue , Ruptura Aórtica/diagnóstico , Ruptura Aórtica/etiologia , Feminino , Seguimentos , Humanos , Hipercolesterolemia/complicações , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/patologia , Hipertensão/complicações , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo
14.
Neurology ; 67(11): 2039-41, 2006 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-17159116

RESUMO

We compared fMRI and cognitive data from nine hormone therapy (HT)-naive women with data from women exposed to either opposed conjugated equine estrogens (CEE) (n = 10) or opposed estradiol (n = 4). Exposure to either form of HT was associated with healthier fMRI response; however, CEE-exposed women exhibited poorer memory performance than either HT-naive or estradiol-exposed subjects. These preliminary findings emphasize the need to characterize differential neural effects of various HTs.


Assuntos
Cognição/efeitos dos fármacos , Estradiol/farmacologia , Estrogênios Conjugados (USP)/farmacologia , Imageamento por Ressonância Magnética , Cognição/fisiologia , Terapia de Reposição de Estrogênios/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/fisiologia
15.
Neurology ; 64(12): 2063-8, 2005 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-15985573

RESUMO

OBJECTIVE: To determine the efficacy of testosterone (T) supplementation on cognition in a sample of men with Alzheimer disease (AD) or mild cognitive impairment (MCI). METHODS: Fifteen patients with AD and 17 patients with MCI aged 63 to 85 years completed a randomized, double-blind, placebo-controlled study. Nineteen participants received weekly intramuscular (IM) injections of 100 mg T enanthate and 13 participants received weekly injections of placebo (saline) for 6 weeks. Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline, week 3, and week 6 of treatment and again after 6 weeks of washout. RESULTS: Peak serum total T levels were raised from baseline an average of 295% in the active treatment group. Improvements in spatial memory (p < 0.05) and constructional abilities (p < 0.05) and verbal memory were evident in the T group. No changes were noted for selective and divided attention or language. Prostate specific antigen did not significantly change during this brief treatment. CONCLUSION: Testosterone supplementation may benefit selective cognitive functions in men with Alzheimer disease and mild cognitive impairment.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Transtornos Cognitivos/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Testosterona/farmacologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Método Duplo-Cego , Humanos , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Fármacos Neuroprotetores/sangue , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Testes Neuropsicológicos , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Testosterona/sangue , Testosterona/uso terapêutico , Resultado do Tratamento
16.
Cell Mol Life Sci ; 62(3): 299-312, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15723166

RESUMO

Recent findings from the Women's Health Initiative (WHI) have raised considerable concern over prolonged use of opposed and unopposed oral conjugated equine estrogen (CEE), given the increased risk of serious adverse effects, including stroke and venous thromboembolic complications. Furthermore, results from the WHI Memory Study (WHIMS) indicated that over 5 years of therapy with Prempro impaired performance on global cognitive tests and nearly doubled the risk of dementia. These surprising findings were contradictory to cumulative evidence from basic science, epidemiological and some intervention studies suggesting hormone therapy was cardioprotective and could potentially reduce the risk of dementia. This review paper focuses on the neurobiology of estrogen, summarizing the clinical evidence for neuroprotective and cognition-enhancing efficacy of estrogen. Further, the paper briefly discusses variables that may account for the unexpected findings of WHIMS, and offers suggestions for future research.


Assuntos
Hormônios Esteroides Gonadais/farmacologia , Fármacos Neuroprotetores/farmacologia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Estrogênios/farmacologia , Feminino , Hormônios Esteroides Gonadais/fisiologia , Humanos
17.
Indian J Cancer ; 41(1): 8-12, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15105573

RESUMO

BACKGROUND: Early detection and multimodality therapy has resulted in an overall improvement of survival among breast cancer patients. Despite a significant shift in the treatment approach from radical mastectomy to breast conservation a significant number of patients develop lymphedema. This study was conducted to evaluate the prevalence and risk factors for development of lymphedema. SETTINGS AND DESIGN: Retrospective analysis for prevalence of lymphedema in a tertiary care regional cancer centre. MATERIAL AND METHODS: Three hundred treated breast cancer patients with a minimum follow up of one year were evaluated for the prevalence and risk factors for lymphedema. Lymphedema was assessed using a serial circumferential measurement method. More than 3 cm difference in circumference is considered as clinical significant lymphedema. Univariate and multivariate analysis were performed for evaluating the risk factors by using the Chi square test and Cox logistic regression analysis. RESULTS: The prevalence of clinically significant lymphedema was 33.5 % and 17.2 % had severe lymphedema. The prevalence of lymphedema was 13.4 % in patients treated with surgery only where as the prevalence was 42.4% in patients treated with surgery and radiotherapy. Stage of the disease, body surface area > 1. 5 m2, presence of co-morbid conditions, post operative radiotherapy and anthracycline based chemotherapy were significant risk factors in univariate analysis where as axillary irradiation and presence of co-morbid conditions have emerged as independent risk factors in multivariate analysis (P < 0.001). CONCLUSION: Post treatment lymphedema continues to be a significant problem following breast cancer therapy. Presence of co-morbid conditions and axillary radiation significantly increases the risk of lymphedema. A combination of axillary dissection and axillary radiation should be avoided whenever feasible to avoid lymphedema.


Assuntos
Neoplasias da Mama/cirurgia , Linfedema/etiologia , Mastectomia Radical Modificada/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Superfície Corporal , Quimioterapia Adjuvante , Distribuição de Qui-Quadrado , Feminino , Seguimentos , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco
18.
Psychoneuroendocrinology ; 29(1): 65-82, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14575730

RESUMO

BACKGROUND: Our laboratory has previously reported that testosterone (T) administration to older men significantly improves cognitive function. This study examined potential changes in insulin-like growth factor (IGF) IGF-I, IGF-II and IGF-related binding proteins in response to T administration in older men and their relationship to cognitive functioning. METHODS: Twenty-five healthy community dwelling volunteers, ranging in age from 50-80 years were randomized to receive weekly intra-muscular (i.m.) injections of either 100 mg T enanthate or placebo (saline) for 6 weeks. Serum hormone levels and cognitive functioning was assessed at baseline and twice during treatment. RESULTS: Significant positive associations between IGF-I and IGF-II and spatial memory, spatial reasoning, and verbal fluency were observed after 6 weeks of T administration. Increased serum T levels from treatment were positively associated with improvement in spatial reasoning performance, whereas estradiol was associated with a decline in divided attention performance. Serum IGF-I, IGF-II and IGFBPs did not change in response to T treatment. CONCLUSIONS: Our results suggest that T, estradiol and IGF-I may have independent and selective effects on cognitive functioning. Positive associations between T levels and cognition are consistent with an effect of androgen treatment, whereas positive associations between IGF-I levels and cognition are reflective of a relationship between endogenous IGF-I levels and cognition.


Assuntos
Cognição/fisiologia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Testosterona/administração & dosagem , Testosterona/fisiologia , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Atenção/fisiologia , Estradiol/sangue , Humanos , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Pessoa de Meia-Idade , Comportamento Espacial/fisiologia , Aprendizagem Verbal/fisiologia
19.
J Hazard Mater ; 99(3): 225-39, 2003 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-12758009

RESUMO

Nickel hydrazinium nitrate (NiHN) and cobalt hydrazinium nitrate (CoHN) were prepared by reacting their respective metal nitrates with hydrazine hydrate at 25 and 65 degrees C. The compounds were characterized by metal content and infrared (IR) spectroscopy. Differential thermal analysis (DTA) results suggest that the nickel complex is relatively more stable than the cobalt complex. The activation energy determined by DTA and ignition delay measurements corresponds to an energy of activation (E(a)) of 80+/-4 kJ/mol for NiHN and that of 150+/-8 kJ/mol for CoHN. Thermo gravimetry (TG) also revealed more rapid decomposition of NiHN than that of CoHN in the temperature region of 215-235 degrees C. High temperature Fourier transform-infrared (FT-IR) studies indicated rupture of the Ni-Co-N bond as the primary step in the thermolysis. As regards sensitivity to mechanical stimuli, NiHN was found to be less impact sensitive while CoHN exhibited less friction sensitivity. The study revealed that NiHN could be used alone as well as in combination with oxidizer/fuel as initiators depending upon the specific requirements. The effect of silver azide and glass on the sensitization of NiHN was also studied. CoHN appears to be an effective ballistic modifier in enhancing burning rates of composite propellants.


Assuntos
Carcinógenos/química , Cobalto/química , Hidrazinas/química , Níquel/química , Substâncias Perigosas , Cinética , Sais/química , Espectrofotometria Infravermelho , Temperatura
20.
Singapore Med J ; 43(5): 226-8, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12188072

RESUMO

AIM: The harmonic scalpel is recently emerging as an alternative surgical tool for dissection and haemostasis and has been extensively used in the field of minimally invasive surgery. We studied the utility and advantages of this instrument over electrocautery for performing modified radical mastectomy. METHODS: The operative and morbidity details of twenty-three breast cancer patients who underwent modified radical mastectomy using the harmonic scalpel were compared with 23 matched controls operated with electrocautery by the same surgical team. RESULTS: There was no significant difference in the operating time between the harmonic scalpel and electrocautery group (104 and 100 mins, p > 0.05). The blood loss (60 +/- 35 ml and 294 +/- 155, p < 0.001) and drainage volume (590 +/- 430 ml and 1,085 +/- 690 ml, p < 0.001) were significantly lower in the harmonic scalpel group. There was a significant reduction of drain days in harmonic scalpel group (mean five and nine days, p < 0.05). There was no significant difference in the seroma rate between two groups (16% and 22%). CONCLUSION: Modified radical mastectomy using harmonic scalpel is feasible and learning curve is short. Harmonic scalpel significantly reduces the blood loss and duration of drainage as compared to electrocautery.


Assuntos
Neoplasias da Mama/cirurgia , Eletrocoagulação/instrumentação , Mastectomia Radical Modificada/métodos , Terapia por Ultrassom/instrumentação , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
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