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1.
Med J Armed Forces India ; 78(1): 36-41, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35035042

RESUMEN

BACKGROUND: Postoperative nausea and vomiting (PONV) is the second most common complaint in the postoperative period, often resulting in increased post anaesthesia care unit (PACU) and hospital stay. Translation of knowledge into consistent practice was considered a major gap. Hence, the present study was undertaken to test the efficacy of locally developed evidence-based institutional protocol for prevention of PONV. METHODS: Phase I consisted of determining the baseline incidence of PONV before introduction of the institutional protocol for PONV prophylaxis. In phase II, educational sessions for anaesthesiologists for PONV prevention and treatment were conducted, after which an institutional protocol was introduced. In phase III, this protocol was implemented, and the incidence of PONV was recorded using the same methodology as in phase I. The rate of adherence to the institutional protocol was also recorded. RESULTS: The incidence of postoperative nausea (PON) dropped significantly from 32.5% in phase I to 20% in phase III (p = 0.033). Similarly, the incidence of postoperative vomiting (POV) decreased from 20.5% in phase I to 9.1% in phase III (p = 0.016). Of all anaesthesiologists, 78.18% were noted to adhere to the protocol in phase III. Incidence of PON and POV was significantly less in patients in whom PONV prophylaxis was administered in adherence to protocol (8.3% vs 57.7%, p < 0.001; 3.6% vs 26.9%, p < 0.001, respectively). CONCLUSION: Evidence-based institutional protocols are effective in significantly reducing the incidence of PONV in adults undergoing noncardiac surgery under anaesthesia. CLINICAL TRIAL NUMBER AND REGISTRY URL: The trial was registered with Clinical Trials Registry of India (http:/ctri.nic.in) (CTRI/2015/12/006432).

3.
J Card Surg ; 35(8): 1865-1870, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32652736

RESUMEN

BACKGROUND: Double-outlet left ventricle (DOLV) is a rare congenital cardiac anomaly. The aorta and the main pulmonary arterial trunk arises predominantly from the left ventricle and is associated with a malaligned ventricular septal defect, various degrees of hypoplasia of the right ventricle, and presence, or absence of pulmonary stenosis. Bi-ventricular repair is the preferred treatment option whenever possible. Multiple techniques for bi-ventricular repair have been described. The best option for DOLV correction is by translocating the pulmonary root from the left ventricle to the right ventricle. In this series, we report four patients who underwent biventricular repair of DOLV with excellent outcomes. METHODS: This is a retrospective study of four patients who underwent surgical correction of DOLV between January 2014 and December 2018. We collected all patient details from the institute patient record system. Echocardiographic data were obtained from the records. Intraoperative charts were reviewed for further information on the surgical procedure and cardiopulmonary bypass. Postoperative data included survival, functional status, and followup echocardiography. RESULTS: Of the four children, three underwent pulmonary root translocation, and one child underwent a Reparation al etage Ventriculaire (REV) procedure. There was no mortality in our series, and all children are in a stable clinical condition in the recent follow-up, and no re-operations or interventions were required following primary surgical correction. CONCLUSION: DOLV is anatomically and surgically a challenging subset. Pulmonary root translocation in this anatomy is technically challenging but safe and superior option when compared to other alternative surgical procedures. Pulmonary root translocation can be performed with excellent results, even in infants.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos/métodos , Ventrículo Derecho con Doble Salida/terapia , Puente Cardiopulmonar , Humanos , Estudios Retrospectivos , Resultado del Tratamiento
4.
Clin Exp Immunol ; 202(2): 226-238, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32557565

RESUMEN

Rheumatoid arthritis (RA) is a chronic autoimmune disease which causes degradation of cartilage and bone. It is well appreciated that the pathogenic hallmark of RA is the mass influx of inflammatory cells into the joint. However, the role that dendritic cells (DC) may play in this inflammatory milieu is still relatively unexplored. Moreover, the contribution this unique synovial microenvironment has on DC maturation is still unknown. Using monocyte-derived DC (MoDC), we established an in-vitro model to recapitulate the synovial microenvironment to explore DC maturation. MoDC treated with conditioned media from ex-vivo synovial tissue biopsy cultures [explant-conditioned media (ECM)] have increased expression of proinflammatory cytokines, chemokines and adhesion molecules. ECM DC have increased expression of CD83 and CC-chemokine receptor (CCR)7 and decreased expression of CCR5 and phagocytic capacity, suggestive of heightened DC maturation. ECM-induced maturation is concomitant with altered cellular bioenergetics, whereby increased expression of glycolytic genes and increased glucose uptake are observed in ECM DC. Collectively, this results in a metabolic shift in DC metabolism in favour of glycolysis. These adaptations are in-part mediated via signal transducer and activator of transcription-3 (STAT-3), as demonstrated by decreased expression of proinflammatory cytokines and glycolytic genes in ECM DC in response to STAT-3 inhibition. Finally, to translate these data to a more in-vivo clinically relevant setting, RNA-seq was performed on RA synovial fluid and peripheral blood. We identified enhanced expression of a number of glycolytic genes in synovial CD1c+ DC compared to CD1c+ DC in circulation. Collectively, our data suggest that the synovial microenvironment in RA contributes to DC maturation and metabolic reprogramming.


Asunto(s)
Artritis Reumatoide/inmunología , Microambiente Celular/inmunología , Células Dendríticas/inmunología , Membrana Sinovial/inmunología , Antígenos CD/inmunología , Artritis Reumatoide/patología , Células Dendríticas/patología , Femenino , Regulación de la Expresión Génica/inmunología , Humanos , Inmunoglobulinas/inmunología , Masculino , Glicoproteínas de Membrana/inmunología , RNA-Seq , Receptores CCR5/inmunología , Receptores CCR7/inmunología , Factor de Transcripción STAT3/inmunología , Membrana Sinovial/patología , Antígeno CD83
5.
Indian J Nephrol ; 29(2): 128-131, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30983755

RESUMEN

Metastatic pulmonary calcification (MPC) has been described in the literature to affect up to 60% of dialysis patients. Several case series of MPC were described in 1960s and 1970s. Patients are generally asymptomatic or may present with acute respiratory distress. This entity is associated with up to 60% mortality. We hereby report a case of chronic kidney disease on maintenance hemodialysis who presented with unexplained recurrent dyspnea despite adequate hemodialysis. She was evaluated and found to have a rare presentation of calciphylaxis.

6.
Ann Oncol ; 29(2): 352-360, 2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29069303

RESUMEN

Background: Genomic aberrations have been identified in metastatic castration-resistant prostate cancer (mCRPC), but molecular predictors of resistance to abiraterone acetate/prednisone (AA/P) treatment are not known. Patients and methods: In a prospective clinical trial, mCRPC patients underwent whole-exome sequencing (n = 82) and RNA sequencing (n = 75) of metastatic biopsies before initiating AA/P with the objective of identifying genomic alterations associated with resistance to AA/P. Primary resistance was determined at 12 weeks of treatment using criteria for progression that included serum prostate-specific antigen measurement, bone and computerized tomography imaging and symptom assessments. Acquired resistance was determined using the end point of time to treatment change (TTTC), defined as time from enrollment until change in treatment from progressive disease. Associations of genomic and transcriptomic alterations with primary resistance were determined using logistic regression, Fisher's exact test, single and multivariate analyses. Cox regression models were utilized for determining association of genomic and transcriptomic alterations with TTTC. Results: At 12 weeks, 32 patients in the cohort had progressed (nonresponders). Median study follow-up was 32.1 months by which time 58 patients had switched treatments due to progression. Median TTTC was 10.1 months (interquartile range: 4.4-24.1). Genes in the Wnt/ß-catenin pathway were more frequently mutated and negative regulators of Wnt/ß-catenin signaling were more frequently deleted or displayed reduced mRNA expression in nonresponders. Additionally, mRNA expression of cell cycle regulatory genes was increased in nonresponders. In multivariate models, increased cell cycle proliferation scores (≥ 50) were associated with shorter TTTC (hazard ratio = 2.11, 95% confidence interval: 1.17-3.80; P = 0.01). Conclusions: Wnt/ß-catenin pathway activation and increased cell cycle progression scores can serve as molecular markers for predicting resistance to AA/P therapy.


Asunto(s)
Acetato de Abiraterona/administración & dosificación , Resistencia a Antineoplásicos/genética , Prednisona/administración & dosificación , Neoplasias de la Próstata Resistentes a la Castración/genética , Vía de Señalización Wnt/genética , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclo Celular , Proliferación Celular , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/genética , Estudios Prospectivos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico
7.
Oncogene ; 35(5): 608-20, 2016 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-25961929

RESUMEN

Glioblastoma can originate from terminally differentiated astrocytes and neurons, which can dedifferentiate to a stem cell-like state upon transformation. In this study, we confirmed that transformed dedifferentiated astrocytes and neurons acquired a stem/progenitor cell state, although they still retained gene expression memory from their parental cell. Transcriptional network analysis on these cells identified upregulated genes in three main pathways: Wnt signaling, cell cycle and focal adhesion with the gene Spp1, also known as osteopontin (OPN) serving as a key common node connecting these three pathways. Inhibition of OPN blocked the formation of neurospheres, affected the proliferative capacity of transformed neurons and reduced the expression levels of neural stem cell markers. Specific inhibition of OPN in both murine and human glioma tumors prolonged mice survival. We conclude that OPN is an important player in dedifferentiation of cells during tumor formation, hence its inhibition can be a therapeutic target for glioblastoma.


Asunto(s)
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Transformación Celular Neoplásica/genética , Glioblastoma/genética , Glioblastoma/terapia , Animales , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , Ratones , Ratones Transgénicos , Terapia Molecular Dirigida , Osteopontina/antagonistas & inhibidores , Osteopontina/biosíntesis , Osteopontina/genética , Osteopontina/metabolismo , Transducción de Señal , Regulación hacia Arriba , Vía de Señalización Wnt/genética
8.
Phytother Res ; 18(1): 87-91, 2004 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-14750208

RESUMEN

Garlic oil was evaluated for gastroprotective activity against ethanol induced ulcers. Reactive oxygen species are involved in the pathogenesis of these ulcers. The possible involvement of garlic oil in restraining the oxidation process produced in gastric tissue was also investigated. The ulcer index, lipid peroxidation and antioxidant enzyme activity (GPx, catalase, SOD) were determined. Pretreatment with garlic oil in doses of 0.25 and 0.5 mg/kg, 30 min before administration of ethanol (1 mL of 100%) caused a decrease in ulcer index and lipid peroxidation and ameliorated the decrease in antioxidant enzyme levels caused by ethanol. The result suggests that garlic oil possesses antioxidant properties and provides protection against ethanol induced gastric injury.


Asunto(s)
Antiulcerosos/farmacología , Ajo , Fitoterapia , Aceites de Plantas/farmacología , Úlcera Gástrica/prevención & control , Animales , Antiulcerosos/administración & dosificación , Antiulcerosos/uso terapéutico , Relación Dosis-Respuesta a Droga , Etanol , Mucosa Gástrica/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Aceites de Plantas/administración & dosificación , Aceites de Plantas/uso terapéutico , Ratas , Ratas Wistar , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patología , Superóxido Dismutasa/efectos de los fármacos
9.
Intern Med J ; 33(8): 350-4, 2003 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12895165

RESUMEN

BACKGROUND: Aspirin is widely used as an antiplatelet agent in the primary and secondary prevention of cardiovascular disease. In order to spare prostacyclin formation and reduce gastrointestinal side-effects, very low doses of aspirin have been introduced. However, it remains unclear whether these low doses are equally effective with respect to inhibition of platelet aggregation. AIMS: In a randomized, controlled study in 60 patients with stable coronary artery disease, the effects on platelet aggregation of five doses (50, 80, 100, 162.5 and 325 mg) of aspirin, which are widely used in clinical practice, given for 70 days, were investigated. Two reagents, adenosine diphosphate (ADP) and epinephrine, were used to induce platelet aggregation in platelet-rich plasma. An age- and sex-matched group of people without coronary artery disease served as the control. RESULTS: ADP- and epinephrine-induced platelet aggregation was 78.2 +/- 12.8% and 76.7 +/- 15.5% of maximum aggregation in the control group. Aspirin inhibited platelet aggregation in a dose-dependent manner. Minimum platelet aggregation was observed at a dose of 325 mg aspirin (27.5 +/- 17.4% with ADP). Doses of 50 and 80 mg aspirin were much less effective in inhibiting platelet aggregation (59.1 +/- 11.4% and 50.3 +/- 12.1% with ADP, respectively). Doses of 100 and 162.5 mg aspirin produced significantly greater inhibition of platelet aggregation than lower doses (36.2 +/- 11.7% and 38.5 +/- 19.8% platelet aggregation with ADP, respectively). CONCLUSION: Our results demonstrate that doses of aspirin less than 100 mg are not as effective at inhibiting platelet aggregation as doses greater than 100 mg.


Asunto(s)
Aspirina/administración & dosificación , Enfermedad Coronaria/sangre , Agregación Plaquetaria/efectos de los fármacos , Adenosina Difosfato/farmacología , Adulto , Anciano , Enfermedad Coronaria/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Epinefrina/farmacología , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad
10.
Acta Neurochir (Wien) ; 144(11): 1165-77, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12434173

RESUMEN

BACKGROUND: Reducible atlanto-axial dislocation (AAD) may cause severe motor and respiratory compromise due to recurrent spinal cord and/or brain stem impingement. To the best of the authors' knowledge, this is the first study concentrating on the classification, the protocol of the surgical management and the outcome of congenital, reducible AAD. METHODS: 109 patients with congenital, reducible AAD underwent posterior stabilization. Their preoperative disability was graded as: I (n=11, 10.09%) no functional disability (a history of minor trauma led to quadriparesis that subsequently improved); II (n=31, 28.44%) independent for activities of daily living with minor disability; III (n=42, 38.53%) partially dependent on others for their daily needs; and, IV (n=25, 22.93%) totally dependent. They were classified into 4 groups depending upon their association with: a normal odontoid and posterior arch of atlas (n=27); a dysplastic odontoid and normal posterior arch (n=25); an assimilated posterior arch (n=49); and, Arnold Chiari malformation type I (n=8). Nine patients with a dysplastic odontoid had a "hypermobile" AAD with an unrestricted backward and forward movement of the axis relative to the atlas in flexion as well as in extension of the neck, respectively. The surgical procedures included Brooks' (n=12) or modified Brooks' C1-2 fusion (n=39); Goel's C1-2 fusion (3); Ransford's contoured rod fusion (n=7); Jain's occipitocervical fusion (n=47); and, transoral decompression and Jain's occipitocervical fusion (n=1). There were 6 peri-operative mortalities in the series. FINDINGS: At follow-up (ranging from 3 months to 6 years; n=86), 64 patients had shown improvement by one grade or more; 8 patients, who had a history of transient quadriparesis but were without neurological deficits at presentation, remained in grade I; 11 had achieved stabilization of neurological functions; while 3 had deteriorated despite adequate radiological reduction of AAD and fusion of the construct. A follow-up of 6 months or more was available in 79 of these 86 patients, in whom a dynamic intrathecal CT scan showed a good osseous union. INTERPRETATION: The patients with congenital reducible AAD, depending on their surgical management, may be classified into four groups. Some patients with a dysplastic odontoid have a "hypermobile" AAD and require special care during intubation, positioning and stabilization. An assimilated posterior arch is often associated with asymmetrical lateral occipito-C1-C2 joint synostosis rendering transarticular screw placement difficult. The various causes of failure of constructs are discussed.


Asunto(s)
Articulación Atlantoaxoidea/anomalías , Luxaciones Articulares/congénito , Fusión Vertebral/métodos , Adolescente , Adulto , Articulación Atlantoaxoidea/patología , Articulación Atlantoaxoidea/cirugía , Tornillos Óseos , Niño , Preescolar , Evaluación de la Discapacidad , Femenino , Estudios de Seguimiento , Humanos , India , Lactante , Luxaciones Articulares/clasificación , Luxaciones Articulares/cirugía , Imagen por Resonancia Magnética , Masculino , Examen Neurológico , Apófisis Odontoides/anomalías , Apófisis Odontoides/patología , Complicaciones Posoperatorias/diagnóstico , Cuadriplejía/clasificación , Cuadriplejía/congénito , Cuadriplejía/cirugía
11.
Methods Find Exp Clin Pharmacol ; 23(5): 255-7, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11712645

RESUMEN

This study was conducted to examine the effects of single dose enalapril (1.6 mg/kg) on platelet aggregation alone and after an intravenous bolus dose of the nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine (L-NNA; 40 mg/kg). Blood samples were collected before and 1, 2 and 6 h after the administration of drugs in rhesus monkeys. Enalapril was administered via a nasogastric tube while L-NNA was administered by the intravenous route. Platelet aggregation was stimulated with adenosine diphosphate (ADP) in platelet rich plasma (PRP). Enalapril significantly inhibited platelet aggregation with a peak effect at 6 h. Upon administration of L-NNA, there was a significant increase in the percentage of platelet aggregation. This effect was partially antagonized by enalapril. The present study demonstrates that enalapril may possess antiaggregatory effects, which may be mediated via nitric oxide mechanisms.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enalapril/farmacología , Óxido Nítrico/fisiología , Agregación Plaquetaria/efectos de los fármacos , Adenosina Difosfato/farmacología , Animales , Inhibidores Enzimáticos/farmacología , Macaca mulatta , Masculino , Óxido Nítrico Sintasa/antagonistas & inhibidores , Nitroarginina/farmacología
12.
Peptides ; 22(9): 1485-9, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11514033

RESUMEN

Adrenomedullin, a multifunctional peptide, is expressed by many surface epithelial cells and, previously, we have demonstrated that adrenomedullin has antimicrobial activity. The oral cavity contains an epithelium that is permanently colonized by microflora, yet infections in a host are rare. We exposed oral keratinocytes to whole, live cells from four microorganisms commonly isolated from the oral cavity, Porphyromonas gingivalis, Streptococcus mutans, Candida albicans and Eikenella corrodens. There was upregulation of protein and gene expression in these cells in response to bacterial suspensions, but not with the yeast, Candida albicans. We propose there is a potential role for microbial products in enhancing mucosal defense mechanisms and that adrenomedullin participates in the prevention of local infection, thus contributing to host defense mechanisms.


Asunto(s)
Antiinfecciosos/metabolismo , Queratinocitos/metabolismo , Mucosa Bucal/metabolismo , Mucosa Bucal/microbiología , Péptidos/metabolismo , Adrenomedulina , Antibacterianos , Northern Blotting , Péptido Relacionado con Gen de Calcitonina/metabolismo , Péptido Relacionado con Gen de Calcitonina/fisiología , Candida albicans , Células Cultivadas , Electroforesis en Gel de Agar , Bacterias Gramnegativas , Bacterias Grampositivas , Humanos , Técnicas para Inmunoenzimas , Queratinocitos/efectos de los fármacos , Queratinocitos/microbiología , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Factores de Tiempo , Regulación hacia Arriba , beta-Defensinas/metabolismo
13.
Otolaryngol Head Neck Surg ; 123(4): 368-76, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11020170

RESUMEN

OBJECTIVE: The goal was to identify factors associated with the outcome of salvage therapy for patients with isolated cervical recurrences of squamous cell carcinoma in the previously treated neck (ICR-PTN). STUDY DESIGN AND SETTINGS: A tumor registry search for ICR-PTN patients was performed at 7 participating institutions, and the charts were reviewed. Kaplan-Meier plots for survival and time until re-recurrence were used to evaluate the significance of associated variables. RESULTS: Median survival and time until re-recurrence were both 11 months. Survival was better in patients with the following characteristics: nonsurgical initial neck treatment, negative initial disease resection margins, no history of prior recurrence, ipsilateral location of the ICR-PTN relative to the primary, and use of surgical salvage. CONCLUSIONS: By pooling the experience of 7 US tertiary care medical centers, we have identified 5 factors that are associated with outcome of salvage therapy for ICR-PTN. SIGNIFICANCE: Consideration of these factors, as well as the reviewed literature, should facilitate patient selection for salvage protocols.


Asunto(s)
Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Causas de Muerte , Neoplasias de Cabeza y Cuello/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/terapia , Terapia Recuperativa , Adulto , Anciano , Análisis de Varianza , Carcinoma de Células Escamosas/patología , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Probabilidad , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia
14.
Mol Med ; 6(5): 450-60, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10952024

RESUMEN

BACKGROUND: Proteases facilitate several steps in cancer progression. To identify proteases most suitable for drug targeting, actual enzyme activity and not messenger RNA levels or immunoassay of protein is the ideal assay readout. MATERIALS AND METHODS: An automated microtiter plate assay format was modified to allow detection of all four major classes of proteases in tissue samples. Fifteen sets of colorectal carcinoma biopsies representing primary tumor, adjacent normal colon, and liver metastases were screened for protease activity. RESULTS: The major proteases detected were matrix metalloproteases (MMP9, MMP2, and MMP1), cathepsin B, cathepsin D, and the mast cell serine proteases, tryptase and chymase. Matrix metalloproteases were expressed at higher levels in the primary tumor than in adjacent normal tissue. The mast cell proteases, in contrast, were at very high levels in adjacent normal tissue, and not detectable in the metastases. Cathepsin B activity was significantly higher in the primary tumor, and highest in the metastases. The major proteases detected by activity assays were then localized in biopsy sections by immunohistochemistry. Mast cell proteases were abundant in adjacent normal tissue, because of infiltration of the lamina propria by mast cells. Matrix metalloproteases were localized to the tumor cells themselves; whereas, cathepsin B was predominantly expressed by macrophages at the leading edge of invading tumors. Although only low levels of urinary plasminogen activator were detected by direct enzyme assay, immunohistochemistry showed abundant protein within the tumor. CONCLUSIONS: This analysis, surveying all major classes of proteases by assays of activity rather than immunolocalization or in situ hybridization alone, serves to identify proteases whose activity is not completely balanced by endogenous inhibitors and which may be essential for tumor progression. These proteases are logical targets for initial efforts to produce low molecular weight protease inhibitors as potential chemotherapy.


Asunto(s)
Neoplasias del Colon/enzimología , Neoplasias Colorrectales/enzimología , Endopeptidasas/metabolismo , Proteoma , Biopsia , Catepsinas/metabolismo , Quimasas , Colon/enzimología , Neoplasias del Colon/patología , Neoplasias Colorrectales/patología , Humanos , Mucosa Intestinal/enzimología , Neoplasias Hepáticas/secundario , Metaloproteinasas de la Matriz/metabolismo , Serina Endopeptidasas/metabolismo , Triptasas
15.
Carcinogenesis ; 21(9): 1721-6, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10964104

RESUMEN

The development of bladder tumors has been associated with a number of causative agents, including schistosomiasis. Schistosome-related cancers show different clinical and pathological features compared with non-schistosome-related bladder cancers, occurring in younger patients, and being predominantly of squamous cell type. This study addresses the difference between squamous and transitional tumor types in the presence of schistosome infection as a measure of the relationship between tumor genotype and phenotype. We have used comparative genomic hybridization to analyze primary muscleinvasive schistosome-related bladder tumors in 54 patients. Twenty-six of these tumors were squamous cell carcinomas; the remaining 28 were of transitional cell type. On average, transitional cell tumors showed 1.8 times the number of chromosomal aberrations as squamous cell tumors (14.4 versus 8.2, P: < 0.001). For both groups combined, the most prevalent genetic alterations were losses of 8p and 18q, and gains of 8q. Transitional cell cancers also showed frequent losses involving 5q, 9p, 10q, 11p and 11q, and gains at 1q and 17q. Loss of 11p was significantly more frequent in TCC than in SCC tumors (50 versus 4%, P: = 0.01). Squamous cell cancers showed more frequent losses of 17p and 18p than transitional tumors, which was clearly significant given the overall reduced frequency of changes in squamous cancers (P: = 0.001 and P: = 0.03, respectively). These data show that different histologic subgroups of bladder tumors are characterized by distinct patterns of chromosomal alterations. The genetic changes found in the transitional cell group are similar to those reported in non-schistosome-related transitional cell tumors, but differ from tumors exhibiting squamous differentiation.


Asunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Transicionales/genética , Esquistosomiasis/complicaciones , Neoplasias de la Vejiga Urinaria/genética , Animales , Carcinoma de Células Escamosas/parasitología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Transicionales/parasitología , Carcinoma de Células Transicionales/patología , Aberraciones Cromosómicas , Amplificación de Genes , Humanos , Estadificación de Neoplasias , Hibridación de Ácido Nucleico , Schistosoma , Neoplasias de la Vejiga Urinaria/parasitología , Neoplasias de la Vejiga Urinaria/patología
16.
J Gastroenterol Hepatol ; 15(7): 737-43, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10937678

RESUMEN

BACKGROUND AND AIMS: The topographic distribution and density of Helicobacter pylori and associated gastritis in the stomach were studied in order to determine which biopsy sites are likely to provide the maximum yield so as to reduce the fallacious results due to sampling error. METHODS: Fifty patients with upper gastrointestinal symptoms were studied. Eleven gastric biopsies from predetermined sites were obtained and subjected to ultra-rapid urease test, imprint cytology and histology. Haematoxylin and eosin stain was used for defining gastritis and other associated histopathological details. Loeffler's methylene blue stain was used to confirm the presence of H. pylori in imprint smears and histological sections. RESULTS: All 50 patients had H. pylori infection and evidence of chronic gastritis at one or more of the 11 biopsy sites. Maximum and minimum percentage positivity were observed at A3 (antral lesser curvature) and B4 (corpus greater curvature), respectively. Various sites in decreasing order of percentage positivity were A3 > A2 > A1 > A4 > B3 > B1 > A5 > B6 > B5 > B2 > B4. Among the biopsies obtained from the corpus, B3 (corpus lesser curvature) was the site with maximum positivity. A3 and B4 had a statistically significant difference in percentage positivity (P < 0.0001) for H. pylori and gastritis. The maximum and minimum density scores of H. pylori and gastritis were found in A3 and the B4, respectively. A3 had a significantly higher (P < 0.0001) mean density score than any other site in the stomach. The difference in the grading of H. pylori between A3 and B3 (sites of maximum positivity in antrum and corpus) was statistically significant (P < 0.0001). A statistically significant (P < 0.001) positive correlation between increasing grades of H. pylori and gastritis was observed at the site of maximum density. Eighty per cent of the patients had antral predominant gastritis and in 82%, H. pylori was predominantly observed in antral biopsies. CONCLUSION: It is concluded that two biopsies taken from A3 are sufficient for confirmation of presence of H. pylori and associated gastritis for initiation of treatment. However, additional biopsies from B3 will help in deciding the topographic pattern of gastritis.


Asunto(s)
Gastritis/microbiología , Helicobacter pylori/aislamiento & purificación , Adulto , Femenino , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis/patología , Humanos , Masculino
17.
Methods Find Exp Clin Pharmacol ; 22(3): 159-62, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10893698

RESUMEN

Angiotensin-converting enzyme is present in the male reproductive system but its role in the physiology of reproduction is not known. To see the effect of angiotensin-converting enzyme on spermatozoal functions, lisinopril, an angiotensin-converting enzyme inhibitor, was administered orally using two different doses (10 and 20 mg/kg/day) to rats. Both short-term (2 weeks) and long-term (6 weeks) effects of the drug were observed. Lisinopril treatment resulted in a marked decrease in sperm density, sperm motility and zona pellucida penetration. Acrosome reaction by spermatozoa obtained from drug-treated animals was significantly lower when compared with spermatozoa from normal animals.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Lisinopril/farmacología , Espermatozoides/efectos de los fármacos , Acrosoma/efectos de los fármacos , Animales , ATPasas Transportadoras de Calcio/metabolismo , Masculino , Ratas , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Espermatozoides/fisiología , Zona Pelúcida/efectos de los fármacos , Zona Pelúcida/metabolismo
18.
Indian J Physiol Pharmacol ; 44(4): 449-55, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11214500

RESUMEN

Nimodipine, a dihydropyridine calcium channel blocker, was administered orally using two different doses (40 mg and 60 mg/kg/day) to rats. Both short term (2 weeks) and long term (6 weeks) effects of the drug were observed. The drug administration resulted in a marked decrease in sperm density, sperm motility and acrozomal reaction. Zona-pellucida penetration by the sperm obtained from drug-treated animals was significantly lower when compared with sperm from normal animals. Nimodipine stimulated Ca2+ ATPase activity in isolated plasma membrane of rate spermatozoa. In conclusion, short term and long term administration of nimodipine has deleterious effect on male reproductive functions in rats.


Asunto(s)
Reacción Acrosómica/efectos de los fármacos , Bloqueadores de los Canales de Calcio/farmacología , ATPasas Transportadoras de Calcio/efectos de los fármacos , Nimodipina/farmacología , Motilidad Espermática/efectos de los fármacos , Reacción Acrosómica/fisiología , Animales , ATPasas Transportadoras de Calcio/metabolismo , Femenino , Masculino , Ratas , Reproducción/efectos de los fármacos , Reproducción/fisiología , Recuento de Espermatozoides , Motilidad Espermática/fisiología , Zona Pelúcida/efectos de los fármacos , Zona Pelúcida/fisiología
19.
J Urol ; 163(1): 163-6; discussion 166-7, 2000 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10604337

RESUMEN

PURPOSE: We define the optimal systematic biopsy regimen to detect carcinoma of the prostate. MATERIALS AND METHODS: A total of 483 consecutive patients referred for an abnormal digital rectal examination and/or prostate specific antigen (PSA) 4.0 ng./ml. or greater underwent transrectal ultrasound and systematic biopsy. Lateral biopsies of the peripheral zone at the base and mid gland were added to the routine sextant biopsy regimen for a total of 10 systematic biopsies of the peripheral zone. Patients with a prostate greater than 50 cc also underwent systematic sextant transition zone biopsy in the mid lobar parasagittal plane. Detection rates of the various regions were assessed. Various biopsy schemes were then created and cancer detection rates were compared using McNemar's test. RESULTS: Of the patients 42% (202 of 483) had cancer on biopsy. Traditional sextant biopsies missed 20%, while a sextant regimen incorporating lateral peripheral zone biopsies of the mid gland and base along with the apex missed 11% of the cancers. The combination of sextant and lateral peripheral zone biopsies (10-biopsy scheme) detected 194 cancers (96%). The 8 missed cancers were detected by lesion directed (5) or transition zone (3) biopsies. Eliminating the mid lobar base biopsies from the systematic 10-biopsy peripheral zone regimen resulting in an 8-biopsy peripheral zone regimen decreased detection from 96% to 95%. CONCLUSIONS: The 6 systematic biopsies of the peripheral zone are inadequate and a minimum of 8, including the apex, mid lobar mid gland, lateral mid gland and lateral base, should routinely be performed.


Asunto(s)
Biopsia con Aguja/métodos , Biopsia con Aguja/estadística & datos numéricos , Neoplasias de la Próstata/patología , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados
20.
Urology ; 54(4): 689-93, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10510929

RESUMEN

OBJECTIVES: To determine whether the number of positive sextant biopsies contributes to the prediction of positive surgical margins, as the value of systematic prostate biopsies in predicting margin status at radical prostatectomy is unclear. METHODS: Consecutive patients (n = 108) who underwent radical retropubic prostatectomy and systematic sextant biopsies were retrospectively evaluated. Serum prostate-specific antigen, digital rectal examination, primary Gleason grade, Gleason score, and the number and location of positive sextant biopsies were recorded for each patient. Radical prostatectomy specimens were evaluated by step-section techniques at 3 to 5-mm intervals. Univariate comparisons for each of these variables was performed between the positive and negative margin groups using the Mann-Whitney U test or chi-square analysis. Logistic regression analysis was performed for these variables. RESULTS: Twenty-two (20.4%) of 108 patients had a positive surgical margin because of extension of the tumor through the capsule. Patients with three or more positive biopsies were at higher risk of having a positive surgical margin (P = 0.009). Patients with bilaterally positive biopsies at either the base or midprostate were more likely to have a positive surgical margin. The risk of a positive surgical margin was not significantly determined by the primary Gleason grade, Gleason score, or prostate-specific antigen. Multivariate logistic regression models were created that consistently demonstrate that the number of positive biopsies was the best predictor of margin status. CONCLUSIONS: This study demonstrated that the number of positive sextant biopsies contributes to the prediction of margin status at radical prostatectomy.


Asunto(s)
Biopsia con Aguja/métodos , Prostatectomía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Anciano , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios Retrospectivos
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