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1.
São Paulo; SMS; 2013. 1 p. ilus.
Non-conventional in Portuguese | Coleciona SUS, COVISA-Producao, Sec. Munic. Saúde SP, Sec. Munic. Saúde SP | ID: biblio-939251
3.
Ann ICRP ; 41(3-4): 318-31, 2012.
Article in English | MEDLINE | ID: mdl-23089032

ABSTRACT

It has been established that naturally occurring radioactive material (NORM) may accumulate at various locations along the oil and gas production process. Components such as wellheads, separation vessels, pumps, and other processing equipment can become contaminated with NORM, and NORM can accumulate in the form of sludge, scale, scrapings, and other waste media. This can create a potential radiation hazard to workers, the general public, and the environment if certain controls are not established. Saudi Aramco has developed NORM management guidelines, and is implementing a comprehensive strategy to address all aspects of NORM management that aim to enhance NORM monitoring; control of NORM-contaminated equipment; control of NORM waste handling and disposal; and protection, awareness, and training of workers. The benefits of shared knowledge, best practice, and experience across the oil and gas industry are seen as key to the establishment of common guidance. This paper outlines Saudi Aramco's experience in the development of a NORM management strategy, and its goals of establishing common guidance throughout the oil and gas industry.


Subject(s)
Environmental Exposure , Occupational Exposure , Oil and Gas Fields , Radiation Monitoring/standards , Radiation Protection/standards , Radioactive Waste/prevention & control , Environmental Exposure/prevention & control , Environmental Exposure/standards , Environmental Policy/legislation & jurisprudence , Government Regulation , Guidelines as Topic , Humans , Industry/standards , Models, Theoretical , Occupational Exposure/prevention & control , Occupational Exposure/standards , Saudi Arabia
4.
5.
Rev. colomb. cir ; 17(2): 7-12, jun. 2002. tab, graf
Article in Spanish | LILACS | ID: lil-325741

ABSTRACT

Objetivo: Mostrar la experiencia en la Fundacion Santa Fé de Bogotá con el abordaje extraseroso con resección de la duodécima costilla para el drenaje de los abscesos subfrénicos. Métodos: Se realiza una revision retrospectiva de las historias clínicas de los pacientes sometidos a drenaje de abscesos subfrénicos por la técnica de Ochsner en el periodo comprendido entre enero de 1995 y diciembre de 2001. Se revisaron datos demográficos, la causa del absceso, métodos díagnósticos, procedimientos quirúrgicos y/o radiológicos, el grado de severidad de la enfermedad calculado por el indice APACHE II en el momento de la cirugía, complicaciones de la cirugía, gérmenes detectados en los cultivos, complicaciones no relacionadas con el procedimiento y los días de hospitalización antes y después de la cirugía. Resultados: Cinco pacientes fueron sometidos a 6 procedimientos de Ochsner por 4 abscesos subfrénicos izquierdos y uno bilateral. Dos pacientes presentaron abscesos por pancreatitis aguda y tres por fístulas gástricas. Todos los díagnósticos se realizaron por TAC. El indice APACHE se pudo calcular en 4 pacientes y la medíana fué de 3,5. A todos se les habia practicado por lo menos un procedimiento abdominal previo y en 3 un drenaje percutáneo fallido. Solo hubo una complicación por el procedimiento y fue la apertura accidental del díafragma. Escherichia coli y Pseudomona sp fueron los principales gérmenes identificados. En todos los pacientes el tratamiento fue efectivo para el drenaje del absceso y la medíana de la hospitalización antes de la cirugía fue de 47 días y de 21 días de postoperatorio. Conclusiones: El drenaje posterior de los abscesos subfrénicos por la tecnica de Ochsner es un procedimiento seguro en quienes el drenaje percutáneo fue fallido y se ofrece como altemativa en aquellos casos en los que el drenaje percutáneo no este indicado.


Subject(s)
Humans , Male , Female , Subphrenic Abscess/surgery , Drainage , Gastric Fistula/complications , Pancreatitis
6.
J Physiol ; 536(Pt 2): 569-82, 2001 Oct 15.
Article in English | MEDLINE | ID: mdl-11600690

ABSTRACT

1. Our goal in this study was to evaluate the effect of haemodynamic overload on cross-bridge (XBr) kinetics in the rabbit heart independently of myosin heavy chain (MHC) isoforms, which are known to modulate kinetics in small mammals. We applied a myothermal-mechanical protocol to isometrically contracting papillary muscles from two rabbit heart populations: (1) surgically induced right ventricular pressure overload (PO), and (2) sustained treatment with propylthiouracil (PTU). Both treatments resulted in a 100 % V3 MHC profile. 2. XBr force-time integral (FTI), evaluated during the peak of the twitch from muscle FTI and tension-dependent heat, was greater in the PO hearts (0.80 +/- 0.10 versus 0.45 +/- 0.05 pN s, means +/- S.E.M., P = 0.01). 3. Within the framework of a two-state XBr model, the PO XBr developed more force while attached (5.8 +/- 0.9 versus 2.7 +/- 0.3 pN), with a lower cycling rate (0.89 +/- 0.10 versus 1.50 +/- 0.14 s(-1)) and duty cycle (0.14 +/- 0.03 versus 0.24 +/- 0.02). 4. Only the ventricular isoforms of myosin light chain 1 and 2 and cardiac troponin I (cTnI) were expressed, with no difference in cTnI phosphorylation between the PO and PTU samples. The troponin T (TnT) isoform compositions in the PO and PTU samples were significantly different (P = 0.001), with TnT2 comprising 2.29 +/- 0.03 % in PO hearts versus 0.98 +/- 0.01 % in PTU hearts of total TnT. 5. This study demonstrates that MHC does not mediate dramatic alterations in XBr function induced by haemodynamic overload. Our findings support the likelihood that differences among other thick and thin filament proteins underlie these XBr alterations.


Subject(s)
Hemodynamics/physiology , Hypertrophy, Right Ventricular/metabolism , Hypertrophy, Right Ventricular/physiopathology , Papillary Muscles/metabolism , Ventricular Myosins/metabolism , Animals , Cardiac Myosins/metabolism , Cross-Linking Reagents/metabolism , Hot Temperature , Models, Biological , Myocardial Contraction/physiology , Myosin Light Chains/metabolism , Papillary Muscles/physiopathology , Pressure , Rabbits , Stress, Mechanical , Troponin I/metabolism , Troponin T/metabolism
7.
Cancer Res ; 60(13): 3599-604, 2000 Jul 01.
Article in English | MEDLINE | ID: mdl-10910074

ABSTRACT

p53 abnormalities constitute the most frequent genetic alterations identified in larynx cancers. p53 overexpression in histologically "tumor-free" surgical margins correlates with a high recurrence rate. However, only 50-60% of tumors overexpress p53. The tumor marker eIF4E is overexpressed in 100% of larynx cancers, and overexpression of eIF4E in histologically "tumor-free" margins predicts a significantly higher recurrence. We undertook this study to correlate the expression of p53 and eIF4E in the tumors and surgical margins of squamous cell cancers of the larynx and to determine their prognostic value. A retrospective analysis was performed on 54 patients who underwent surgery for squamous cell cancers of the larynx. Patient and tumor characteristics were reviewed, and the time to recurrence was noted. Paraffin-embedded sections from the tumors and surgical margins were immunostained with antibodies to eIF4E and p53, and a qualitative analysis was performed. All 54 patients (100%) overexpressed eIF4E in the primary tumor, whereas 25 of 53 patients (47%) were p53 positive. Thirty-two of the 54 patients (59%) had eIF4E-positive margins. All 6 of 53 patients (11%) with p53-positive margins also overexpressed eIF4E in the margins. There was a significant correlation between p53 and eIF4E being positive in the margins (Spearman's correlation coefficient, P = 0.03). Twenty-one of the 25 patients (84%) that recurred, including the 6 patients with p53-positive margins, had eIF4E-positive margins. Hence, although the univariate analysis showed that nodal status and both eIF4E and p53 expression in the margins were significant predictors of recurrence (P < 0.05), in the multivariate analyses only nodal status (P < 0.001) and eIF4E in the margins (P < 0.001) were significant predictors of recurrence. Kaplan-Meier analysis demonstrated that the disease-free intervals for eIF4E-positive margins were significantly shorter than eIF4E-negative margins (P = 0.0007). There was no additional effect to the combination of positive p53 and eIF4E margins (P = 0.21). The overexpression of eIF4E in the margins appears to be a more sensitive indicator of recurrence and may be an earlier event in the process of tumorigenesis than p53.


Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/pathology , Peptide Initiation Factors/analysis , Tumor Suppressor Protein p53/analysis , Analysis of Variance , Carcinoma, Squamous Cell/surgery , Disease-Free Survival , Eukaryotic Initiation Factor-4E , Female , Follow-Up Studies , Genes, p53 , Humans , Laryngeal Neoplasms/surgery , Male , Middle Aged , Neoplasm Staging , Peptide Initiation Factors/genetics , Predictive Value of Tests , Prognosis , Proto-Oncogene Mas , Retrospective Studies , Time Factors , Treatment Outcome
8.
Circulation ; 101(5): 541-6, 2000 Feb 08.
Article in English | MEDLINE | ID: mdl-10662752

ABSTRACT

BACKGROUND: Host defense system activation occurs with cardiopulmonary bypass (CPB) and is thought to contribute to the pathophysiological consequences of CPB. Complement inhibition effects on the post-CPB syndrome were tested with soluble complement receptor-1 (sCR1). METHODS AND RESULTS: Twenty neonatal pigs (weight 1.8 to 2.8 kg) were randomized to control and sCR1-treated groups. LV pressure and volume, left atrial pressure, pulmonary artery pressure and flow, and respiratory system compliance and resistance were measured. Preload recruitable stroke work, isovolumic diastolic relaxation time constant (tau), and pulmonary vascular resistance were determined. Pre-CPB measures were not statistically significantly different between the 2 groups. After CPB, preload recruitable stroke work was significantly higher in the sCR1 group (n=5, 46.8+/-3.2x10(3) vs n=6, 34.3+/-3.7x10(3) erg/cm(3), P=0.042); tau was significantly lower in the sCR1 group (26.4+/-1.5, 42.4+/-6. 6 ms, P=0.003); pulmonary vascular resistance was significantly lower in the sCR1 group (5860+/-1360 vs 12 170+/-1200 dyn. s/cm(5), P=0.009); arterial PO(2) in 100% FIO(2) was significantly higher in the sCR1 group (406+/-63 vs 148+/-33 mm Hg, P=0.01); lung compliance and airway resistance did not differ significantly. The post-CPB Hill coefficient of atrial myocardium was higher in the sCR1 group (2.88+/-0.29 vs 1.88+/-0.16, P=0.023). CONCLUSIONS: sCR1 meaningfully moderates the post-CPB syndrome, supporting the hypothesis that complement activation contributes to this syndrome.


Subject(s)
Cardiopulmonary Bypass/adverse effects , Heart Diseases/prevention & control , Lung Diseases/prevention & control , Postoperative Complications/prevention & control , Protective Agents/therapeutic use , Receptors, Complement/therapeutic use , Actin Cytoskeleton/chemistry , Actin Cytoskeleton/drug effects , Actin Cytoskeleton/physiology , Animals , Blood Pressure/drug effects , Calcium/metabolism , Heart Diseases/etiology , Heart Diseases/physiopathology , Heart Function Tests , Lung Diseases/etiology , Lung Diseases/physiopathology , Oxygen/metabolism , Protein Conformation , Respiratory Function Tests , Swine , Time Factors
9.
J Clin Oncol ; 17(9): 2909-14, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10561370

ABSTRACT

PURPOSE: Complete excision of cancer is guided by histologic assessment of surgical margins. Molecular markers may be more sensitive in identifying malignant cells. eIF4E, a eukaryotic protein synthesis initiation factor, is found elevated in all head and neck squamous cell cancers (HNSCC). In a preliminary study using Western blots and a retrospective study using immunohistochemistry, eIF4E elevation in histologically tumor-free surgical margins correlated with a higher local-regional recurrence. We wanted to confirm this hypothesis in a prospective study. PATIENTS AND METHODS: Immunohistochemical analysis of surgical margins and tumors with an antibody to eIF4E was performed on all newly diagnosed HNSCC patients who underwent surgical resection for their disease between January 1996 and December 1997. RESULTS: All 65 patients had elevated levels of eIF4E in the tumors. Thirty-six patients (55%) had elevated eIF4E in histologically tumor-free margins, and 20 of these patients (56%) have had local-regional recu rrences. Twenty-nine patients (45%) had no elevation of eIF4E in the margins, and only two of these patients (6.9%) have had recurrences. Cox regression analysis showed that elevated eIF4E in the margins was an independent prognostic factor (P =.009) for recurrence. The Kaplan-Meier curves for the probability of nonrecurrence were significantly different for positive and negative eIF4E margins (P =. 0001, log-rank test). CONCLUSION: In histologically tumor-free surgical margins, elevated levels of eIF4E predict a significantly increased risk of recurrence. Elevated levels of eIF4E in tumor margins may identify patients who could benefit from additional therapy.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/chemistry , Head and Neck Neoplasms/chemistry , Peptide Initiation Factors/analysis , Analysis of Variance , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Eukaryotic Initiation Factor-4E , Female , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/surgery , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Neoplasm, Residual , Prognosis , Prospective Studies , Regression Analysis , Treatment Outcome
10.
Laryngoscope ; 109(8): 1253-8, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10443829

ABSTRACT

OBJECTIVE: The translation initiation factor eIF4E (4E) when overexpressed in mammalian cells results in their oncogenic transformation. 4E facilitates the synthesis of two powerful tumor angiogenic factors (VEGF and FGF-2) by selectively enhancing their translation. 4E is overexpressed not only in all head and neck squamous cell cancers but also in some dysplastic margins. Tumorigenesis in the head and neck is proposed to be a multistep process preceded by clinically evident precancerous lesions. Molecular events underlie the histological changes that herald transformation. We wanted to study the role of 4E in tumorigenesis and further elucidate its causal role in angiogenesis. METHODS: An immunohistochemical analysis with antibodies to 4E, VEGF, and basic (b)-FGF was performed on 115 specimens of the head and neck representing various stages of histological progression of malignancy. This was correlated with mean vessel density (MVD) using factor VIII. RESULTS: There were 41 cases of hyperplasia and low-grade dysplasia, 40 cases of high-grade dysplasia and 34 cases of cancer. There was a significant increase in the percent of cases expressing 4E from low-grade dysplasia through tumor. However, for VEGF and b-FGF the significant increase was only seen between the tumor group and dysplastic groups and no significant increase was noted between low-grade and high-grade dysplasia There was a significant increase in MVD from low- (10.7+/-1) to high-grade grade dysplasia (18.0+/-2.3). This increase was even more striking for the 4E positive cases. CONCLUSION: 4E elevation is correlated with progressive cell transformation in the head and neck. Its correlation with VEGF, b-FGF, and MVD potentiates its possible role in angiogenesis.


Subject(s)
Endothelial Growth Factors/genetics , Fibroblast Growth Factor 2/genetics , Gene Expression/genetics , Head and Neck Neoplasms/genetics , Lymphokines/genetics , Neoplasms, Squamous Cell/genetics , Peptide Initiation Factors/genetics , Protein Isoforms/genetics , Antibodies, Neoplasm/genetics , Cell Line, Transformed , Eukaryotic Initiation Factor-4E , Head and Neck Neoplasms/pathology , Humans , Immunohistochemistry , Neoplasm Staging , Precancerous Conditions , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
11.
Micron ; 30(3): 235-44, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10420642

ABSTRACT

The application of focused ion beam (FIB) machining in several technologies aimed at microstructure fabrication is presented. These emergent applications include the production of micromilling tools for machining of metals and the production of microsurgical tools. An example of the use of microsurgical manipulators in a circulatory system measurement is presented. The steps needed to transform the laboratory fabrication of these tools and manipulators into a routine FIB production process are discussed. The ion milling of three-dimensional cavities by the exact solution of a mathematical model of the FIB deflection is demonstrated. A good agreement between the model calculation and the ion beam control has been obtained for parabolic and cosine cross-section features with planes of symmetry.


Subject(s)
Microscopy, Electron, Scanning/methods , Microsurgery/instrumentation , Animals , Gallium , Mice , Microcirculation/physiology , Microcirculation/ultrastructure , Microscopy, Electron, Scanning/instrumentation , Microsurgery/methods , Models, Theoretical , Rats
12.
Arch Otolaryngol Head Neck Surg ; 125(2): 177-82, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10037284

ABSTRACT

BACKGROUND: The proto-oncogene eIF4E has been found to be elevated in head and neck squamous cell carcinomas. In an earlier prospective study overexpression of eIF4E, detected by Western blot analysis, in histologically normal surgical margins correlated with an increased local-regional recurrence rate during a 1-year follow-up. OBJECTIVE: To test the reverse hypothesis that absence of overexpression of eIF4E in the surgical margins is a predictor for long-term survival in patients with squamous cell carcinoma of the head and neck. DESIGN: A retrospective analysis was performed on 31 patients who underwent surgery for squamous cell carcinoma of the larynx or hypopharynx. Immunohistochemical analysis was used to detect eIF4E on paraffin embedded sections of the tumor and the histologically negative surgical margins. RESULTS: All 31 patients overexpressed eIF4E in the tumors. Thirteen patients had no detectable level of eIF4E in the margins, and only 1 had a local-regional recurrence. The average disease-free interval in this group of patients was 82.08 months. The remaining 18 patients all overexpressed eIF4E in the surgical margins (eIF4E score range, 5-80). Twelve (67%) of these patients developed a recurrence; the average disease-free interval was 31.95 months. Cox regression analysis showed that eIF4E in the margin (P= .01), nodes (P= .06), site (P= .02), and age (P= .02) had significant effects on the disease-free interval. The Kaplan-Meier survival curves were significantly different for eIF4E-positive and eIF4E-negative margins (P = .002). CONCLUSIONS: eIF4E in the surgical margins is an independent prognostic factor and its absence in surgical margins may predict long-term survival. Detecting eIF4E in the margins may improve survival by determining which patients would benefit from further resection or adjuvant therapy.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/pathology , Hypopharyngeal Neoplasms/pathology , Laryngeal Neoplasms/pathology , Peptide Initiation Factors/analysis , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Disease-Free Survival , Eukaryotic Initiation Factor-4E , Female , Humans , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/surgery , Hypopharynx/pathology , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/surgery , Larynx/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Prognosis , Proto-Oncogene Mas , Retrospective Studies , Survival Rate
13.
Rev. colomb. cir ; 13(3): 181-184, sept. 1998.
Article in Spanish | LILACS | ID: lil-328532

ABSTRACT

Las heridas de tratamiento hospitalario son una entidad frecuente y aunque en Colombia no se conoce su epidemiologia, se sabe que no son un numero despreciable. El objetivo de este trabajo fue el de conocer la epidemiologia de las heridas en pacientes hospitalizados, en un periodo de 1 año, especificamente las heridas quirurgicas, por pie diabetico, ulceras por presion, ulceras varicosas y laparostomias. Además, quisimos investigar que especialidad las trata y quienes son los encargados de las cuidados básicos de estas. Enviamos un formato con su respectivo instructivo a hospitales de las diferentes regiones del pais, logrando la participacion de 11 de estos hospitales. Obtuvimos como resultados que de 185.405 egresos hospitalarios durante el año de 1995, 50.9 por ciento presentaba herida quirurgica; 0.17 por ciento, ulceras por presion; 0.14 por ciento, heridas por pie diabetico; 0.08 por ciento, ulceras varicosas; y 0.25 por ciento, laparostomias. De los pacientes con herida quirurgica, presentaron infeccion global 6.12 por ciento. En todas las heridas, el manejo básico era realizado por las enfermeras y en algunos casos tambien por auxiliares de enfermeria y/o medicos. El servicio de Cirugia General fue el encargado de tratar la herida quirurgica, las ulceras varicosas, las heridas por pie diabetico y las laparostomias, en la gran mayoria de los hospitales. Cirugia Plastica, Medicina Interna, Cirugia Vascular y Dermatologia fueron especialidades que, en orden de frecuencia, tambien trataron heridas en estos pacientes. Se plantea la necesidad de establecer un seguimiento y registro completo de las heridas en los hospitales como parte del tratamiento integral de estas.


Subject(s)
Surgical Wound Infection/epidemiology
14.
Ann Surg ; 227(5): 756-6l; discussion 761-3, 1998 May.
Article in English | MEDLINE | ID: mdl-9605667

ABSTRACT

OBJECTIVE: The objective of this study is to determine if high eukaryotic initiation factor 4E (eIF4E) overexpression (sevenfold elevation or more over benign breast tissue) is associated with a worse clinical outcome. SUMMARY BACKGROUND DATA: Dysregulation of cellular functions by selective overexpression of specific proteins can lead to malignant transformation. The overexpression of eIF4E preferentially increases translation of mRNAs with long, G-C rich 5'-untranslated regions. Selective gene products, such as tumor neoangiogenic factors, ornithine decarboxylase, and cyclin D1, are upregulated. METHODS: One hundred fourteen breast specimens were analyzed and eIF4E overexpression was quantified by Western blot analysis. Quantification for eIF4E protein level was accomplished using a rabbit anti-eIF4E antibody and colorimetric development of Western blots using nitro blue tetrazolium and 5-bromo-4-chloro-3-indolyl phosphate. The blots were scanned and analyzed by densitometry. Treatment, pathologic, and clinical outcome data variables were analyzed. Statistical analysis was performed to determine if eIF4E overexpression is associated with breast cancer clinical outcome. RESULTS: In the 55 benign specimens, the mean eIF4E expression was 1.1+/-0.4 fold (mean +/- standard deviation). All 59 malignant breast carcinoma specimens were noted to have eIF4E overexpression (range, 1.9-fold to 30.6-fold), with a mean overexpression of 10.8+/-6.3-fold. The mean level of eIF4E expression in malignant specimens was higher than benign specimens (p < 0.05, unpaired t test). The degree of eIF4E overexpression appears to be independent of T and N stage. In the 21 patients with eIF4E overexpression of less than sevenfold, there was one cancer recurrence but no cancer-related deaths. In the 38 patients with high eIF4E overexpression (sevenfold or more), 14 patients had breast cancer recurrences (p = 0.03, log rank test), of whom 11 have died from the disease (p = 0.04, log rank test). The average follow-up interval in this study was 40 months. CONCLUSIONS: Patients with stage I to III breast cancer and high eIF4E overexpression had a higher rate of cancer recurrence and a higher rate of cancer-related death when compared to similar-stage breast cancer patients with low eIF4E overexpression. Therefore, eIF4E protein overexpression may be of prognostic value in stage I to III breast carcinoma.


Subject(s)
Breast Neoplasms/metabolism , Neoplasm Proteins/metabolism , Peptide Initiation Factors/metabolism , Blotting, Western , Breast Neoplasms/pathology , Disease-Free Survival , Eukaryotic Initiation Factor-4E , Female , Humans , Neoplasm Recurrence, Local , Prognosis , Retrospective Studies , Treatment Outcome
16.
Circulation ; 94(3): 472-6, 1996 Aug 01.
Article in English | MEDLINE | ID: mdl-8759091

ABSTRACT

BACKGROUND: This study examined cardiac troponin T (cTnT) isoform expression in patients who had undergone surgery at Duke University Medical Center (Durham, NC) between December 1, 1993, and January 31, 1995, to correct congenital heart defects. The human heart expresses four cTnT isoforms (cTnT1 through cTnT4) whose sequence differences result from combinatorial alternative splicing of two exons. We have previously shown that cTnT4 is expressed at higher levels in severely failing hearts from transplant patients. In this study, we tested the hypothesis that congenital heart defects that have a more negative effect on myocardial function increase cTnT4 expression. We used the presence or absence of drug treatment for heart failure or congested circulation before surgery and the duration of inotropic support after corrective surgery as indicators of the pathophysiological state of the heart just before surgery. METHODS AND RESULTS: Right atrial appendage tissue was collected from 34 patients, 6 days to 35 years old (median age, 3.4 months). The amounts of the cTnT1 through cTnT4 isoforms, measured as a percentage of total cTnT, were determined from Western blots probed with MAb13-11, a cTnT-specific monoclonal antibody. We found that cTnT4 expression correlated positively with the duration of inotropic support and was higher in patients who received drug treatment before surgery than in those who did not. Furthermore, we found that the percent of cTnT4 was significantly higher in hearts with congenital defects that caused congestive failure than in hearts with tetralogy of Fallot. CONCLUSIONS: These findings suggest that in patients with congenital cardiac defects, cTnT4 expression is modulated by heart failure and is increased in hearts that are more hemodynamically stressed.


Subject(s)
Heart Defects, Congenital/enzymology , Heart Defects, Congenital/surgery , Isoenzymes/metabolism , Myocardium/enzymology , Troponin/metabolism , Adolescent , Adult , Biomarkers , Child , Child, Preschool , Female , Heart Defects, Congenital/physiopathology , Humans , Infant , Infant, Newborn , Male , Troponin T
17.
Am J Physiol ; 266(6 Pt 1): C1795-802, 1994 Jun.
Article in English | MEDLINE | ID: mdl-8023908

ABSTRACT

We examined the myofibril biochemical, structural, and biophysical properties of C2C12, a mouse skeletal muscle cell line (American Type Culture Collection), to assess whether force development and the sensitivity of the myofilaments to calcium could be measured in C2C12 myotubes and whether a cardiac contractile protein, troponin T, is expressed and incorporated into C2C12 myofibrils. When myoblasts fused and differentiated into myotubes, expression of myofilament proteins was initiated. Multiple cardiac and skeletal muscle troponin T isoforms were coexpressed. Cardiac troponin T expression increased and then decreased with time. Fluorescence immunocytochemistry demonstrated incorporation of cardiac troponin T isoforms into the myofibrils. At the time of the biophysical studies, mean myotube diameter was 12 microns (range 5-25 microns), and mean length was 290 microns (range 130-520 microns). The estimated maximum force developed by chemically skinned myotubes at 6-7 days poststarvation, 0.88 +/- 0.12 microN (mean +/- 95% confidence interval, n = 5), was significantly less (P < 0.05) than that at 10-13 days poststarvation, 1.12 +/- 0.12 microN (n = 7). The force-pCa relation yielded a Hill coefficient of 2.9 +/- 0.6 (n = 7) and half-maximal activation at pCa of 5.77 +/- 0.20. The demonstration that the biophysical properties of C2C12 cells can be measured and that cardiac and skeletal muscle troponin T isoforms are incorporated and colocalized into myofibrils suggest that these cells could be a useful model to assess the effects of exogenous native and mutated cardiac and skeletal contractile protein isoforms on myofilament function.


Subject(s)
Cell Line/metabolism , Cell Line/physiology , Muscles/metabolism , Muscles/physiology , Actin Cytoskeleton/metabolism , Animals , Calcium/metabolism , Calcium/pharmacology , Cell Line/ultrastructure , Compliance , Culture Media , Immunohistochemistry , Isomerism , Mice , Muscle Contraction , Muscle Proteins/metabolism , Muscles/ultrastructure , Myocardium/metabolism , Troponin/metabolism , Troponin T
18.
Pediatr Res ; 35(5): 550-4, 1994 May.
Article in English | MEDLINE | ID: mdl-8065836

ABSTRACT

The inhibitory hemodynamic effects of the Bezold-Jarisch reflex in the adult animal, which play a role in the response to disease states, are elicited by veratridine and are mediated by vagal afferents. We tested whether the reported excitatory response to veratridine in the fetal animal may be caused by a maturational phase in the Bezold-Jarisch response. The effects of proprananol and atropine on the hemodynamic response to veratridine were examined at 124-141 d (mean, 133 d) of gestation in 11 fetal lambs instrumented long-term (instrumentation, 111-129 d of gestation). Seven lambs had intact vagal nerves, and four had bilateral cervical vagotomies. Veratridine injected into the superior vena cava (0.3 to 2.8 micrograms/kg) and the left atrium (0.2 to 0.8 microgram/kg) increased heart rate, arterial pressure, and left ventricular output, with the responses to left atrial injections occurring more rapidly. Propranolol markedly inhibited the increase in arterial pressure; atropine had no effect. Neither carbocaine, perfused around the cervical vagi, nor bilateral transection of the vagal nerves altered the hemodynamic excitatory response to veratridine. These findings demonstrate that the fetal excitatory response to veratridine is not mediated by vagal afferents, indicating the Bezold-Jarisch reflex does not undergo a maturational change from an excitatory reflex to an inhibitory one and suggesting the maturational loss of a sympathetically mediated hemodynamic reflex.


Subject(s)
Fetus/drug effects , Hemodynamics/drug effects , Veratridine/pharmacology , Afferent Pathways/drug effects , Afferent Pathways/physiology , Animals , Atropine/pharmacology , Blood Pressure/drug effects , Cardiac Output/drug effects , Embryonic and Fetal Development/physiology , Female , Fetus/physiology , Heart Rate/drug effects , Hemodynamics/physiology , Maternal-Fetal Exchange , Pregnancy , Propranolol/pharmacology , Reflex/drug effects , Reflex/physiology , Sheep , Vagotomy , Vagus Nerve/drug effects , Vagus Nerve/physiology
19.
Ultrastruct Pathol ; 18(1-2): 137-40, 1994.
Article in English | MEDLINE | ID: mdl-8191620

ABSTRACT

A renal biopsy demonstrated the presence of both glomerulocystic disease (GCD) and lupus glomerulonephropathy in a patient who was admitted for an unrelated disease and was found to have proteinuria and renal failure. Of 12 adult patients with GCD reported in the literature, some form of glomerulonephropathy was demonstrated in 3. One of the 3 had the membranous type of lupus glomerulonephropathy. When family members of previously reported cases of GCD have been examined, "occult" cases of GCD were frequently identified. GCD is probably a much more frequent disease than the relatively small number of published cases would lead one to believe. In adults GCD is often asymptomatic and will only become symptomatic if another renal disease, such as lupus glomerulonephropathy, is superimposed.


Subject(s)
Kidney Diseases, Cystic/pathology , Lupus Nephritis/pathology , Female , Humans , Kidney Diseases, Cystic/complications , Kidney Glomerulus/pathology , Kidney Glomerulus/ultrastructure , Lupus Nephritis/complications , Middle Aged
20.
J Pharmacol Exp Ther ; 264(1): 249-55, 1993 Jan.
Article in English | MEDLINE | ID: mdl-8093727

ABSTRACT

Various changes in the function of dopamine neurons have been proposed to underly the development of behavioral sensitization to the locomotor stimulant effects of d-amphetamine. The present study examined the relative importance of two such mechanisms after both short (3-4 days off) and longer (10-14 days off) withdrawals from repeated amphetamine or saline injection (1 mg/kg/day, days 1-5 and 8-12). First, single-unit recording was used to examine the sensitivity of impulse-regulating somatodendritic autoreceptors located on mesoaccumbens dopamine neurons in the rat ventral tegmental area. Second, in vivo microdialysis was used to examine the ability of amphetamine challenge to increase extracellular dopamine levels in the rat nucleus accumbens. Amphetamine-treated rats exhibited robust behavioral sensitization at both time points as compared to saline-treated rats. At 3 to 4 days off, autoreceptor subsensitivity was observed in the ventral tegmental area of amphetamine-treated rats, but there was no significant change in the ability of amphetamine to increase extracellular dopamine levels in nucleus accumbens. However, after 10 to 14 days off, autoreceptor subsensitivity was no longer observed, but amphetamine challenge resulted in a significantly greater increase in extracellular dopamine levels in amphetamine-treated as compared to saline-treated rats. These findings suggest that autoreceptor subsensitivity is a transient effect which may be related to the development of sensitization, whereas enhancement of amphetamine-stimulated dopamine release does not accompany early stages of behavioral sensitization, but may be involved in the persistence of the phenomenon after longer withdrawal periods.


Subject(s)
Amphetamine/pharmacology , Dopamine/metabolism , Receptors, Dopamine/drug effects , Animals , Behavior, Animal/drug effects , Dopamine Agents/pharmacology , Dose-Response Relationship, Drug , Ergolines/pharmacology , Male , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Quinpirole , Rats , Rats, Sprague-Dawley , Receptors, Dopamine/physiology , Sensitivity and Specificity , Stimulation, Chemical , Tegmentum Mesencephali/drug effects , Time Factors
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