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1.
Phys Rev Lett ; 114(8): 082501, 2015 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-25768759

RESUMO

A pair of transverse wobbling bands is observed in the nucleus ^{135}Pr. The wobbling is characterized by ΔI=1, E2 transitions between the bands, and a decrease in the wobbling energy confirms its transverse nature. Additionally, a transition from transverse wobbling to a three-quasiparticle band comprised of strong magnetic dipole transitions is observed. These observations conform well to results from calculations with the tilted axis cranking model and the quasiparticle rotor model.

2.
Neoplasma ; 58(3): 217-26, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21391738

RESUMO

The purpose of the present study was to identify site-specific prognostic biomarkers in patients with oral squamous cell carcinoma (OSCC). For this purpose, Epidermal growth factor receptor (EGFR), Stat3, H-ras, c-myc, p53, cyclin D1, p16, Rb and Bcl-2 were localized immunohistochemically in buccal mucosa carcinoma (n=74) and tongue carcinoma (n=61) patients. Expression of markers was compared between buccal mucosa and tongue carcinoma and assessed for their prognostic value in site-specific manner. On comparison, only cyclin D1 showed significant difference in expression with higher accumulation in tongue tumors (r=+0.177, p=0.039). Moreover, univariate survival analysis showed that in buccal mucosa patients, loss of p16 and overexpression of H-ras were significant prognosticators for relapse-free survival (RFS) and overall survival (OS), respectively. However, in Cox multivariate analysis, they lost their significance after adjusting for significant clinicopathological parameters. On the other hand, in tongue cancer patients, Cox multivariate analysis showed that for RFS, Stat3 and c-myc, and for OS, Stat3, Bcl-2 and p53 were significant prognosticators after adjusting for significant confounding factors. Our findings indicated that buccal mucosa and tongue carcinoma exhibit different biological behavior which is reflected in prognosis. Therefore, this approach might be helpful to precisely identify patients for more effectively tailored treatment strategy.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/mortalidade , Neoplasias Bucais/mortalidade , Neoplasias da Língua/mortalidade , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Prognóstico
3.
Bull Environ Contam Toxicol ; 81(4): 373-6, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18679559

RESUMO

Soil, water and rice grain samples from field trials conducted under the IPM and non-IPM modules in Kaithal (Haryana) region were analyzed for pendimethalin, atrazine, lindane and chlorpyriphos, and in Dehradun (Uttarakhand) region, samples were analyzed for carbendazim only. The pesticide residues were found below the detectable limit in the soil and water samples of the Kaithal region. From Dehradun region the residues of carbendazim in rice grains were detected at 0.001 mg/kg level, and in soil they were in the range of 0.03-0.001 mg/kg. The insecticides applied in IPM as well as non-IPM trials in both regions were observed to be below the prescribed maximum residue level.


Assuntos
Grão Comestível/química , Resíduos de Praguicidas/análise , Solo/análise , Água/análise , Agricultura , Cromatografia Gasosa , Cromatografia Líquida de Alta Pressão , Eletroquímica , Concentração de Íons de Hidrogênio , Controle de Insetos , Oryza/química , Espectrofotometria Ultravioleta
4.
Int J Biol Markers ; 22(2): 132-43, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17549669

RESUMO

In this study an attempt was made to establish the significance of a battery of molecular alterations and thereby identify risk predictors in oral carcinogenesis. For this purpose, EGFR, Stat3, H-ras, c-myc, p53, cyclin D1, p16, Rb, Ki-67 and Bcl-2 were localized immunohistochemically in normal mucosa (n=12), hyperplasia (n=35), dysplasia (n=25), early stage carcinoma (n=65) and advanced stage carcinoma (n=70). Deregulation occurred at an early stage and the number of alterations increased with disease progression. Using multivariate logistic regression analysis, the significant risk predictor for hyperplasia from normal mucosa was Ki-67 (OR=5.75, p=0.021); the significant risk predictors for dysplasia from hyperplasia were EGFR (OR=12.96, p=0.002), Stat3 (OR=17.16, p=0.0001), p16 (OR=5.50, p=0.039) and c-myc (OR=5.99, p=0.052); the significant risk predictors for early stage carcinoma from dysplasia were p53 (OR=6.63, p=0.0001) and Rb (OR=3.81, p=0.056); and the significant risk predictors for further progression were EGFR (OR=5.50, p=0.0001), Stat3 (OR=4.49, p=0.0001), H-ras (OR=4.05, p=0.001) and c-myc (OR=2.99, p=0.015). Cyclin D1 holds a key position linking upstream signaling pathways to cell cycle regulation. Gene products of the mitogenic signaling pathway play an equally significant role as cell cycle regulatory proteins in the hyperplasia-dysplasia-early-advanced-carcinoma sequence and together may provide a reference panel of markers for use in defining premalignant lesions and predicting the risk of malignant transformation and tumor progression.


Assuntos
Carcinoma de Células Escamosas/patologia , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Transformação Celular Neoplásica , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/citologia , Valor Preditivo dos Testes , Valores de Referência , Língua/patologia , Neoplasias da Língua/patologia
5.
Int J Biol Markers ; 21(3): 175-83, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17013800

RESUMO

The present study sought to explore the occurrence of signal transducer and activator of transcription 3 (Stat3) in patients with oral squamous cell carcinoma (n=135) and its potential relationship with clinicopathological parameters and survival. Stat3 expression was studied by immunohistochemistry. Cytoplasmic or nuclear localization of Stat3 was observed in 62% of patients, whereas only nuclear Stat3 expression was found in 44%. Stat3 positivity in early-stage patients was 45% compared to 79% in advanced-stage patients. However, early-stage Stat3-positive patients showed a gradual increase in staining intensity, with intense staining seen in 52% of the tumors compared to 18% in Stat3-positive advanced-stage patients, where a gradual decrease in intensity expression was observed (p=0.001). Stat3 showed a significant positive correlation with disease stage (p=0.001), nodal status (p=0.033) and tumor size (p=0.001). Multivariate survival analysis using the Cox proportional hazard regression model showed that nuclear Stat3 was a significant independent prognosticator for both relapse-free survival (p=0.014) and overall survival (p=0.042) in early-stage patients. Our results indicated that Stat3 activation is an early event in oral squamous cell carcinoma and represents a potential risk factor for poor prognosis in early-stage patients.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Fator de Transcrição STAT3/biossíntese , Adulto , Carcinoma de Células Escamosas/mortalidade , Feminino , Expressão Gênica , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Análise Multivariada , Análise de Sobrevida
6.
Int J Biol Markers ; 21(2): 74-80, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16847809

RESUMO

There is growing interest in assessing multistep carcinogenesis and predicting its course using different molecular markers. TP53 is a tumor suppressor gene and appears to be one of the molecular targets of tobacco-related carcinogens in oral cancer. The present study evaluated the role of p53 expression in patients with leukoplakia and carcinoma of the tongue. p53 expression was studied by immunohistochemistry. All patients with leukoplakia of the tongue were male tobacco users. Nuclear staining of p53 was observed in 79% of those patients. Fifty percent, 25% and 4% of the patients expressed 1+, 2+ and 3+ nuclear staining, respectively. When leukoplakia patients were graded according to histopathology, 67% had hyperplasia and 33% had dysplasia. Nuclear p53 accumulation was 88% in hyperplasia and 62% in dysplasia. In patients with tongue cancer, nuclear accumulation of p53 was seen in only 19% of the tumors, with a staining intensity of 1+ in 13%, 2+ in 2% and 3+ in 4% of the tumors. The prevalence of nuclear p53 positivity (79%) was significantly higher in patients with leukoplakia than in patients with tongue cancer (19%; chi2 = 34.32, r = -0.45, df = 1, p = 0.0001; odds ratio (OR) = 16.66, 95% CI, 5.25-52.86). Therefore, leukoplakia patients who show p53 expression have a higher risk of developing tongue cancer than those who do not show p53 expression. As the percentage of positivity of nuclear p53 was very low, none of the clinicopathological parameters or disease status showed any significant association with it. The interesting finding is that none of the female cancer patients showed nuclear p53 expression. Therefore, p53 accumulation is believed to be an early event in neoplastic progression of the tongue.


Assuntos
Carcinoma/metabolismo , Regulação Neoplásica da Expressão Gênica , Genes p53 , Leucoplasia Oral/metabolismo , Neoplasias da Língua/metabolismo , Proteína Supressora de Tumor p53/biossíntese , Adulto , Núcleo Celular/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
8.
J Assoc Physicians India ; 53: 205-7, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15926605

RESUMO

Pica is an eating disorder associated with ingestion of variety of non-food substances. A postpartum patient who presented with acute flaccid quadriparesis was detected to have severe hypokalemia. After extensive investigations for cause of hypokalemia, history of geophagia (clay-eating) was obtained. Approach to hypokalemia and health hazards of pica are discussed.


Assuntos
Hipopotassemia/etiologia , Pica/complicações , Quadriplegia/etiologia , Adulto , Eletrocardiografia , Feminino , Humanos
9.
J Assoc Physicians India ; 52: 619-22, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15847354

RESUMO

AIMS: To study the clinical profile and outcome of critically ill patients suffering from leptospirosis with organ dysfunction and correlate mortality with individual risk factors. METHODS: A study of critically ill patients suffering from leptospirosis was carried out in the Medical Intensive Care Unit of a tertiary centre of a metropolitan city between 1st June 2002 and 31st May 2003. All the patients in whom diagnosis was confirmed by ELISA IgM antibody testing underwent thorough clinical examination and necessary biochemical investigations. They received standard antimicrobial therapy and extensive supportive therapy as required. Mortality was correlated with individual risk factors. RESULTS: Out of 834 total admissions in this period, 60 (7.2%) patients suffered from leptospirosis. There were 48 males and 12 females with age ranging from 12 to 60 years, mean age being 40 years. The clinical manifestations varied from fever (58 patients), jaundice (38), subconjunctival haemorrhages (24), to altered sensorium (22). All the patients had evidence of severe sepsis. Forty six patients had multiple organ dysfunction syndrome (MODS) and 26 required ventilatory support. The total mortality in leptospirosis patients was 52% which was much higher compared to the total MICU mortality (31.4%) in the same period. CONCLUSION: Leptospirosis is an important infection associated with high mortality when associated with organ dysfunction. The poor prognostic factors are preponderance of male sex, alcohol dependence, age group > 50 years, MODS, acute respiratory distress syndrome (ARDS), presence of acidosis and need for mechanical ventilation. However, timelyintervention and intensive therapy can save many young lives.


Assuntos
Doenças Endêmicas/estatística & dados numéricos , Unidades de Terapia Intensiva , Leptospirose/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Criança , Estudos de Coortes , Estado Terminal , Países em Desenvolvimento , Quimioterapia Combinada , Feminino , Humanos , Índia/epidemiologia , Leptospirose/diagnóstico , Leptospirose/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Penicilinas/uso terapêutico , Medição de Risco , Distribuição por Sexo , Esteroides/uso terapêutico , Taxa de Sobrevida
10.
J Assoc Physicians India ; 52: 992-3, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15884461

RESUMO

Vesicular mole is best regarded as a benign neoplasia of the chorion with malignant potentials. In India, the prevalence is one in four hundred pregnancies. We present one such case who presented with thyrotoxicosis and pulmonary edema.


Assuntos
Mola Hidatiforme/complicações , Síndrome do Desconforto Respiratório/etiologia , Tireotoxicose/etiologia , Neoplasias Uterinas/complicações , Adulto , Feminino , Humanos , Mola Hidatiforme/epidemiologia , Índia/epidemiologia , Gravidez , Prevalência , Neoplasias Uterinas/epidemiologia
11.
Antimicrob Agents Chemother ; 47(7): 2264-72, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12821478

RESUMO

The influenza virus neuraminidase (NA) inhibitors zanamivir and oseltamivir were introduced into clinical practice in various parts of the world between 1999 and 2002. In order to monitor the potential development of resistance, the Neuraminidase Inhibitor Susceptibility Network was established to coordinate testing of clinical isolates collected through the World Health Organization influenza surveillance network from different regions of the world (M. Zambon and F. G. Hayden, Antivir. Res. 49:147-156, 2001). The present study establishes the baseline susceptibilities prior to and shortly after the introduction of the NA inhibitors. Over 1000 clinical influenza isolates recovered from 1996 to 1999 were tested. Susceptibilities were determined by enzyme inhibition assays with chemiluminescent or fluorescent substrates with known NA inhibitor-resistant viruses as controls. The 50% inhibitory concentrations (IC(50)s) depended upon the assay method, the drug tested, and the influenza virus subtype. By both assays, the mean zanamivir IC(50)s were 0.76, 1.82, and 2.28 nM for the subtype H1N1 (N1), H3N2 (N2), and B NAs, respectively, and the oseltamivir IC(50)s were 1.2, 0.5, and 8.8 nM for the N1, N2, and B NAs, respectively. The drug susceptibilities of known zanamivir- and oseltamivir-resistant viruses with the NA mutations E119V, R292K, H274Y, and R152K fell well outside the 95% confidence limits of the IC(50)s for all natural isolates. Sequence analysis of the NAs of viruses for which the IC(50)s were above the 95% confidence limits and several control isolates for which the IC(50)s were in the normal range revealed variations in some previously conserved residues, including D151, A203, T225, and E375 (N2 numbering). Known resistance mutations are both influenza virus subtype and drug specific, but there was no evidence of naturally occurring resistance to either drug in any of the isolates.


Assuntos
Acetamidas/farmacologia , Antivirais/farmacologia , Neuraminidase/genética , Orthomyxoviridae/efeitos dos fármacos , Ácidos Siálicos/farmacologia , DNA Viral/análise , Farmacorresistência Viral , Fluorescência , Guanidinas , Humanos , Medições Luminescentes , Neuraminidase/química , Orthomyxoviridae/genética , Oseltamivir , Estrutura Terciária de Proteína , Piranos , Zanamivir
12.
J Clin Microbiol ; 41(2): 742-50, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12574276

RESUMO

The increasing use of influenza virus neuraminidase (NA) inhibitors (NIs) necessitates the development of reliable methods for assessing the NI susceptibility of clinical isolates. We evaluated three NA inhibition assays against a panel of five clinical isolates each of influenza virus A/H1N1, A/H3N2, and B strains and four viruses with a defined resistance genotype (R292K, H274Y, R152K, and E119V). For fluorometric enzyme assay (FA) 1 (FA-1), 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid (MUNANA) at 100 microM was used as the substrate, with pretitration of the virus input. For FA-2, MUNANA at 200 microM was used as the substrate, with a fixed 1:10 dilution of input virus. For the chemiluminescence (CL) assay, the 1,2-dioxetane derivative of sialic acid at 100 microM was used as the substrate, with pretitration of the virus. Four different operators repeated the assays several times in a blinded fashion with both zanamivir and oseltamivir carboxylate (GS4071) to determine intra- and interassay variations. Mean 50% inhibitory concentration (IC(50)) values were lower and generally less variable with the CL assay. FA-1 displayed greater variation than the CL assay or FA-2 and the highest IC(50) values with zanamivir; FA-2 showed the highest values with oseltamivir, particularly for influenza virus B, and was more variable with zanamivir than was the CL assay. All three assays detected 40-fold or greater changes in IC(50) values for the resistant viruses with at least one drug. Mixing experiments, whereby increasing fractions (0, 20, 40, 60, 80, and 100%) of NA from a known NI-resistant virus were mixed with the corresponding NI-sensitive parental NA, indicated that the resolution of IC(50) values was clearer with the CL assay than with FA-2 for two of the resistant variants (R152K and E119V). The FA and CL methods were reliable for the detection of NI resistance, but all assays have certain limitations. Based on reproducibility, ease of automation, time required for the assay, and greater sensitivity, the CL assay was selected for future susceptibility testing of influenza virus isolates circulating globally.


Assuntos
Inibidores Enzimáticos/farmacologia , Neuraminidase/antagonistas & inibidores , Orthomyxoviridae/efeitos dos fármacos , Farmacorresistência Viral , Humanos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Orthomyxoviridae/isolamento & purificação , Especificidade por Substrato
13.
J Assoc Physicians India ; 50: 592-4, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12164419

RESUMO

Rhinocerebral mucormycosis (RCM) is a rare but often fatal condition characterized by aggressive necrotizing infection originating from nose and spreading to paranasal sinuses, orbit and central nervous system. Although Fungi and spores of mucorales show minimal intrinsic pathogenicity towards normal persons, they can initiate fulminant infections in patients with underlying debilitating conditions. A case of RCM in a pregnant woman with diabetic keto-acidosis successfully treated by supportive care, amphotericin B and surgery is reported.


Assuntos
Infecções do Sistema Nervoso Central/diagnóstico , Cetoacidose Diabética/complicações , Mucormicose/diagnóstico , Infecções Oportunistas/diagnóstico , Doenças dos Seios Paranasais/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico , Gravidez em Diabéticas/complicações , Adulto , Infecções do Sistema Nervoso Central/complicações , Feminino , Humanos , Mucormicose/complicações , Doenças dos Seios Paranasais/complicações , Gravidez
14.
Int J Biol Markers ; 17(1): 49-55, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-11936586

RESUMO

The purpose of this study was to examine the association of telomerase activity with clinical and histopathological prognostic variables in primary breast cancer (n=64). Telomerase activity in breast cancer was also compared with that in benign (n=10) and non-malignant tissues (n=8; post-lumpectomy tissues histopathologically defined as containing no residual tumor). The parameter was assessed using the Telomerase PCR ELISA kit. Values above OD 0.120 were considered positive. Estrogen and progesterone receptors (ER and PgR) were assayed by the dextran-coated charcoal method and levels >10 fmol/mg cytosol protein were taken as positive. Telomerase activity was detected in 20% and 50% of the patients with benign lesions and primary breast cancer, respectively, and in 50% of post-lumpectomy breast tissues histopathologically defined as containing no residual tumor. Telomerase activity was present in all stages of breast carcinoma and showed a significant inverse correlation with lymph node status (p=0.006), lymphatic invasion (p=0.035) and necrosis (p=0.033). Moreover, when stage II patients were grouped according to nodal involvement, a trend towards significance was observed (p=0.055). No correlation was observed with ER and PgR. The results of our study suggest that telomerase activity might be associated with the presence of cancer cells. Furthermore, telomerase activation may occur early in breast cancer and may be periodically downregulated during subsequent tumor progression.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/enzimologia , Telomerase/biossíntese , Adulto , Idoso , Diferenciação Celular , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Índia , Metástase Linfática , Menopausa , Pessoa de Meia-Idade , Progesterona/metabolismo , Prognóstico , Receptores de Estrogênio/biossíntese , Receptores de Progesterona/biossíntese , Telomerase/metabolismo
15.
Dis Colon Rectum ; 44(4): 523-33, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11330579

RESUMO

PURPOSE: The goal was to investigate the prognostic value of various molecular markers like CEA, Cyclin D1, Bcl-2, c-Myc, p53, p21ras, Ki-67, CD44, Factor VIII-related antigen, cytokeratin-19, adenoma antigen, and prolactin in patients with Dukes B and Dukes C colorectal adenocarcinoma. METHODS: These molecular markers were localized immunohistochemically in nonmalignant (n = 36) and malignant (n = 98) diseases of the colorectum. Data were analyzed statistically using the SPSS software program. The patients with colorectal cancer were followed for a period of five years or their death within that period. RESULTS: The expression of carcinoembryonic antigen, Cyclin D1, Bcl-2, CD44, cytokeratin-19 and prolactin was significantly higher in malignant diseases (P < 0.05), whereas, p21ras was found to be significantly higher in nonmalignant diseases (P = 0.002) as compared with their respective counterparts. Besides Dukes stage, multivariate analysis indicated a significantly reduced relapse-free survival in patients expressing CD44 and cytokeratin-19 (P < 0.005). Similarly, besides Dukes stage, multivariate analysis indicated a significantly poor overall survival in patients expressing CD44, cytokeratin-19 and prolactin (P < 0.01). In patients with Dukes B disease, only cytokeratin-19 and CD44 expression attained statistical significance (P < 0.05), whereas in patients with Dukes C disease, CD44, p21ras- and c-Myc expression attained statistical significance (P < 0.018). Also, a multivariate analysis in relation to treatment given was performed using CD44 and cytokeratin-19. CONCLUSION: Besides Dukes stage, multivariate analysis of all the studied molecular markers showed that patients expressing CD44 and cytokeratin-19 had a significantly reduced relapse-free and poor overall survival. Moreover, patients expressing both these markers (CD44 and cytokeratin-19) had the lowest significant relative risk for developing recurrence than patients with both markers negative when treated with surgery followed by adjuvant chemotherapy as compared with patients treated with surgery alone. Thus, in patients with colorectal cancer, immunohistochemical localization of CD44 and cytokeratin-19 may be included as a part of routine pathologic evaluation along with conventional prognostic factors.


Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Proteínas de Neoplasias/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adulto , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Imuno-Histoquímica , Queratinas/metabolismo , Masculino , Análise Multivariada , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
16.
J Assoc Physicians India ; 49: 257-8, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11225141

RESUMO

A series of eight cases of methyl alcohol poisoning resulting from consumption of adulterated alcohol is presented. Most of the patients had blurring of vision followed by coma, metabolic acidosis and hemodynamic unstability (SBP < 90 mmHg) on admission to medical ICU. Early recognition and prompt initiation of treatment lead to successful recovery in five of these patients. Analysis of correlation between clinical and biochemical indicators of severity and indication for various therapeutic interventions are discussed.


Assuntos
Metanol/intoxicação , Adolescente , Adulto , Feminino , Humanos , Unidades de Terapia Intensiva , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Intoxicação/diagnóstico , Intoxicação/terapia , Diálise Renal
17.
Dis Colon Rectum ; 44(1): 119-27, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11805572

RESUMO

PURPOSE: This study assessed the role of prolactin in patients with Dukes B and C colorectal carcinoma. METHODS: Circulating prolactin and carcinoembryonic antigen were assayed using immunoradiometric assay and radioimmunoassay kits, respectively, in preoperative blood (n = 98) and tumor-draining venous blood (n = 34) samples of colorectal carcinoma patients. Immunohistochemical localization of prolactin (n = 98), carcinoembryonic antigen (n = 98), and prolactin receptors (n = 56) was performed. The expression of prolactin messenger ribonucleic acid (n = 50) and prolactin receptor messenger ribonucleic acid (n = 50) was studied by reverse transcriptase polymerase chain reaction. Further, prolactin amplimer was sequenced. RESULTS: Preoperative prolactin and carcinoembryonic antigen levels were significantly higher in patients with colorectal carcinoma than in controls (prolactin, P = 0.001; carcinoembryonic antigen, P = 0.0001). Univariate survival analysis showed that Dukes stage, histologic grade, and circulating prolactin were significant prognostic factors for determining overall survival (Dukes stage, P = 0.00001; histologic grade, P = 0.005; prolactin, P = 0.001). In multivariate analysis, besides Dukes stage, circulating prolactin emerged as the most significant independent prognostic factor influencing overall survival. Preoperative prolactin levels showed excellent significant correlation with response to therapy and progression of disease. A significant tenfold higher mean concentration of prolactin was observed in tumor-draining venous blood than in peripheral blood (P = 0.0001). Diffuse cytoplasmic staining for prolactin was seen in 51 percent (50/98) of the colorectal carcinomas. Prolactin messenger ribonucleic acid expression was seen in 88 percent (44/50) of the colorectal carcinomas. Sequence analysis of the 234-bp prolactin amplimer revealed that the sequence was homologous to exon 5 of pituitary prolactin messenger ribonucleic acid. CONCLUSION: These multiple approaches confirmed that prolactin is produced by colorectal carcinoma cells. Looking at its prognostic value and correlation with disease activity, it may provide new insights into treatment for patients with colorectal carcinoma.


Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/metabolismo , Neoplasias Colorretais/sangue , Neoplasias Colorretais/metabolismo , Hormônios Ectópicos/sangue , Prolactina/sangue , RNA Mensageiro/genética , Adenocarcinoma/genética , Adulto , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/genética , Feminino , Hormônios Ectópicos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Prolactina/genética , RNA Mensageiro/sangue , Receptores da Prolactina/sangue , Receptores da Prolactina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de RNA , Análise de Sobrevida
18.
Eur J Surg Oncol ; 26(6): 540-7, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11034803

RESUMO

AIMS: The aim of this study was to evaluate the prognostic value of pre-operative prolactin (PRL) in conjunction with established prognosticators, and the risk of disease relapse in patients with early and advanced breast cancer. To confirm the hypothesis that PRL is produced by breast tumours molecular analysis of PRL, using immunohistochemistry, mRNA by RT-PCR and direct sequencing, was performed. Furthermore, presence of prolactin receptors (PRLR) was evaluated by immunohistochemical localization in these patients. METHODS: In 111 breast cancer patients, pre-operative PRL was determined by an immunoradiometric assay (IRMA) method. Immunohistochemical localization of PRL (IHL-PRL) and PRLR was performed on formalin-fixed, paraffin-embedded tissue sections. Expression of PRL mRNA was carried out by reverse transcriptase polymerase chain reaction (RT-PCR). RT-PCR PRL amplimer was sequenced and compared with human pituitary PRL amplimer. RESULTS: Fifty-eight per cent (64/111) of the patients had hyperprolactinaemia (PRL520.0 ng/ml). With increasing tumour size, a higher incidence of hyperprolactinaemia was noted which was statistically significant (r=0.34, P=0.0001). In stage III patients, and in node positive patients, the incidence of hyperprolactinaemia was significantly higher compared to their respective counterparts (stage II vs stage III, r=0.37, P=0.00006; node negative vs node positive, r=0.30, P=0.001). Hyperprolactinaemic patients had a significantly higher risk of developing recurrent/metastatic disease and a higher mortality risk as compared to patients with PRL <20.0 ng/ml. The multivariate survival analysis indicated that apart from disease stage, prognosis of patients with pre-operative hyperprolactinaemia was poorer than that of patients with PRL <20.0 ng/ml. Seventy-eight per cent (87/111) of the tumours showed positive immunoreactivity with PRL antibody indicating that PRL, or a similar molecule, is produced ectopically by breast tumours. PRL mRNA expression using RT-PCR confirmed the de novo synthesis of PRL. PRL mRNA expression was seen in 52% (33/63) of tumours. Sequence analysis of the 234 bp PRL amplimer revealed that the sequence was homologous to the sequence of exon 5 of human pituitary PRL mRNA. Furthermore, PRLR were present in 80% of tumours detected by immunohistochemical localization. A significant positive correlation was noted between IHL-PRL and PRLR (r=0.26, P=0.006). CONCLUSIONS: This multifaceted study of PRL suggests that breast cancer cells produce PRL and that this ectopically produced PRL may act as a major local growth promoter via autocrine and paracrine mechanisms. It may provide new insights into endocrine treatment of breast cancer.


Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/metabolismo , Substâncias de Crescimento/biossíntese , Prolactina/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Feminino , Substâncias de Crescimento/sangue , Substâncias de Crescimento/genética , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Prolactina/sangue , Prolactina/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores da Prolactina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco
19.
Ann Surg Oncol ; 7(4): 305-11, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10819372

RESUMO

BACKGROUND: The aim was to investigate the expression of a panel of biomarkers such as prolactin (PRL), p53, Bcl-2, c-erb B2, Ki-67, CD44, and factor VIII-related antigen (FVIII-RA) in primary tumors of stage II and stage III breast cancer and its correlation with disease prognostication. METHODS: The streptavidin-biotin peroxidase complex technique was used for the detection of these antigens. Cytoplasmic staining pattern was observed for PRL, Bcl-2, and Ki-67. Staining pattern for p53 was nuclear. Membranous and/or cytoplasmic staining was noted for c-erb B2 and CD44. Microvessel staining was noted for FVIII-RA. RESULTS: Of the 93 primary breast tumors analyzed, positivity for PRL was noted in 82%, for p53 in 56%, for Bcl-2 in 73%, for c-erb B2 in 68%, and for Ki-67 and CD44 in 78% each. The microvessel count (MVC) for FVIII-RA ranged from 0.0 to 29.0, with a median of 6.0, which was used as a cutoff. MVC > or = 6.0 was noted in 51% of breast tumors. With increasing tumor size, the higher frequency of positivity of MVC > or = 6.0 (P = .0001), CD44 (P = .001), PRL (P = .002), and c-erb B2 (P = .008), and higher frequency of Bcl-2 negativity (P = .033), was noted. In stage III patients, a higher positivity of the following biomarkers was noted, compared with stage II patients: MVC > or = 6.0 (P = .0004), PRL (P = .0002), c-erb B2 (P = .001), and CD44 (P = .005). Further, Bcl-2 positivity was significantly lower in patients with stage III disease compared with those with stage II disease (P = .024). In patients with nodal involvement, the frequency of c-erb B2 (P = .006), MVC > or = 6.0 (P = .011), and PRL (P = .032) was higher than in those without nodal involvement. Moreover, in these patients, with the increase in the number of involved lymph nodes, there was a significant increase in frequency of CD44+ (P = .0004) and PRL+ (P = .013) tumors. Abnormal expression of one biomarker was seen in 7% of tumors, of two biomarkers in 4%, of three in 15%, of four in 19%, of five in 28%, of six in 20%, and of all seven biomarkers in 7% of tumors. The frequency of an increasing number of biomarkers coexpressed was higher in stage III patients compared with stage II patients (P = .00003). In the total number of patients (n = 93), tumors with Bcl-2 negativity (P = .00001), MVC > or = 6.0 (P = .001), PRL positivity (P = .02), and CD44 positivity (P = .034) had a significantly poorer overall survival (OS) compared with their respective counterparts. In stage II patients (n = 40), only p53 expression was significantly associated with reduced relapse-free survival (P = .009) and OS (P = .040). In multivariate analysis, p53 expression was an independent prognostic factor that influenced relapse-free survival (P = .034) of stage II breast cancer patients. However, it failed to attain statistical significance for OS. In stage III patients (n = 53), tumors with Bcl-2 negativity (P = .0005) and MVC > or = 6.0 (P = .039) had a significantly poorer OS compared with their respective counterparts. In multivariate analysis of stage III patients, Bcl-2 was the only independent prognostic factor (P = .001) for predicting OS. There was a significant association between coexpression of the biomarkers and OS (P = .001). The OS rates decreased with the increase in number of abnormally expressed biomarkers. CONCLUSIONS: p53 expression in primary tumors was an independent prognostic factor that influenced relapse-free survival in patients with stage II disease. In stage III patients, lack of Bcl-2 expression was independently associated with a poor prognosis and, thus, may be an indicator of aggressive phenotype.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Análise de Regressão , Proteína Supressora de Tumor p53/metabolismo
20.
J Assoc Physicians India ; 48(11): 1070-3, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11310383

RESUMO

OBJECTIVES: This study was undertaken to determine incidence, clinical features, microbiological flora and prognosis of patients with nosocomial pneumonia (NP) in medical intensive care unit (ICU). Also to study impact of comorbid illnesses, intubation and mechanical ventilation on outcome. METHODS: In this prospective study over a period of one year 89 patients were detected to have nosocomial pneumonia amongst 948 total admissions in ICU. All these 89 patients were investigated radiologically, microbiologically and biochemically. Mortality in these patients was correlated with various factors using chi-square test. RESULTS: Incidence of NP was 9.38%. Enteric gram-negative organisms were commonest isolates (61.9%), followed by Staph aureus (29.8%). Sixty five (73%) patients had severe pneumonia, 47 (52.8%) required intubation and 42 (47.2%) mechanical ventilation. Total mortality was 19 out of 89 (21.3%). High mortality was associated with habits like smoking (33.3%), age group over 60 years (27.3%), presence of comorbid illness like DM and COAD (38.5%), complications like ARDS (61.3%, p < 0.001) or sepsis with end organ failure (73.7%, p < 0.001) and need of intubation (36.2%) or mechanical ventilation (40.5%, p < 0.005). CONCLUSION: Nosocomial pneumonias constitute important problem in medical ICU and are associated with high mortality. Patients with advanced age, co-morbid illness, ARDS and end organ failure are at high risk for mortality. However with intensive supportive care and appropriate antibiotics many such lives can be saved.


Assuntos
Infecção Hospitalar/diagnóstico , Infecção Hospitalar/epidemiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Antibacterianos/administração & dosagem , Distribuição de Qui-Quadrado , Infecção Hospitalar/tratamento farmacológico , Feminino , Humanos , Incidência , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Pneumonia/tratamento farmacológico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Distribuição por Sexo , Taxa de Sobrevida
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