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1.
Endoscopy ; 37(3): 240-3, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15731940

RESUMEN

BACKGROUND AND STUDY AIMS: Scintigraphy is the currently accepted method for evaluation of gastric emptying. Although quantitative, this method is complicated, time-consuming, and costly. If a simple endoscopic technique was available for those instances when quantification of an emptying abnormality is not needed, the same clinical information could be obtained in less time and with resource savings. Our aims in this study were therefore to assess the technical feasibility, tolerability, and safety of unsedated transnasal esophagogastroscopy (T-EG) as a technique for qualitative assessment of gastric emptying. METHODS: The study was done in two phases. In the first phase, 18 volunteers (ten men, eight women) underwent T-EG at 4 hours, 5 hours, or 6 hours after ingestion of a standard meal used for scintigraphic evaluation of gastric emptying without radiolabeling. In the second phase, ten volunteers underwent T-EG after scintigraphic imaging had demonstrated complete gastric emptying. RESULTS: Subjects in both phases tolerated the procedure well and completed the study. In the first phase, 13 of 15 volunteers exhibited complete gastric emptying at 6 hours (87%), while two (13%) revealed some particulate matter in the stomach at that time. In the second phase, one of the ten volunteers exhibited a small amount of solid food residue in the stomach despite documentation of scintigraphic complete emptying. CONCLUSIONS: Evaluation of gastric emptying by unsedated T-EG is both feasible and safe. In healthy, asymptomatic individuals, complete gastric emptying of solid food may take as long as 6 hours.


Asunto(s)
Vaciamiento Gástrico/fisiología , Gastroscopios , Estómago/fisiología , Adulto , Anciano , Seguridad de Equipos , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Gastroscopía/métodos , Humanos , Intubación Gastrointestinal/instrumentación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Cintigrafía , Valores de Referencia , Estómago/diagnóstico por imagen
2.
J Clin Oncol ; 20(9): 2267-76, 2002 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-11980997

RESUMEN

PURPOSE: To compare survival and toxicity in adult patients treated with low-dose (50.4 Gy/28 fractions) versus high-dose (64.8 Gy/36 fractions) localized radiation therapy (RT) for supratentorial low-grade astrocytoma, oligodendroglioma, and mixed oligoastrocytoma. PATIENTS AND METHODS: From 1986 to 1994, 203 eligible/analyzable patients were randomized: 101 to low-dose RT, 102 to high-dose RT. Almost half were younger than 40 years, and 95% had grade 2 tumors. Histologic subtype was astrocytoma (or mixed oligo-astrocytoma with astrocytoma dominant) in 32% of patients and oligodendroglioma (or oligoastrocytoma with oligodendroglioma dominant) in 68%. Tumor diameter was less than 5 cm in 35% of patients, and 41% of tumors showed some degree of contrast enhancement. Extent of resection was gross total in 14% of patients, subtotal in 35%, and biopsy only in 51%. RESULTS: At the time of the present analysis, 83 patients (41%) are dead, and median follow-up is 6.43 years in the 120 who are still alive. Survival at 2 and 5 years is nonsignificantly better with low-dose RT; survival at 2 and 5 years was 94% and 72%, respectively, with low-dose RT and 85% and 64%, respectively, with high-dose RT (log rank P =.48). Multivariate analysis identified histologic subtype, tumor size, and age as the most significant prognostic factors. Survival is significantly better in patients who are younger than 40 years and in patients who have oligodendroglioma or oligo-dominant histology. Grade 3 to 5 radiation neurotoxicity (necrosis) was observed in seven patients, with one fatality in each treatment arm. The 2-year actuarial incidence of grade 3 to 5 radiation necrosis was 2.5% with low-dose RT and 5% with high-dose RT. CONCLUSION: This phase III prospective randomized trial of low- versus high-dose radiation therapy for adults with supratentorial low-grade astrocytoma, oligodendroglioma, and oligoastrocytoma found somewhat lower survival and slightly higher incidence of radiation necrosis in the high-dose RT arm. The most important prognostic factors for survival are histologic subtype, tumor size, and age. The study design of the ongoing intergroup trial in this population will be discussed.


Asunto(s)
Glioma/radioterapia , Neoplasias Supratentoriales/radioterapia , Adulto , Anciano , Distribución de Chi-Cuadrado , Fraccionamiento de la Dosis de Radiación , Relación Dosis-Respuesta en la Radiación , Femenino , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Radioterapia/efectos adversos , Dosificación Radioterapéutica , Estadísticas no Paramétricas , Neoplasias Supratentoriales/patología , Análisis de Supervivencia , Resultado del Tratamiento
3.
Aliment Pharmacol Ther ; 16(5): 945-50, 2002 May.
Artículo en Inglés | MEDLINE | ID: mdl-11966503

RESUMEN

BACKGROUND: The treatments available for diabetic gastropathy are frequently ineffective. Clinical observations suggest that clonidine, an a-2 adrenergic agonist, may improve diabetic gastropathy symptoms. AIMS: To establish whether a single oral dose of clonidine alters the gastric emptying of a solid meal in 10 patients with diabetic gastropathy and their matched controls. A secondary goal was to compare two methods of analysis of the data from gastric emptying studies. METHODS: Clonidine, 0.3 mg, or a matched placebo were administered orally in a double-blind fashion. RESULTS: Only three of the 10 patients showed an increased gastric residual volume. Gastric emptying rates were comparable in patients and controls. Clonidine had no significant effect on gastric emptying in the controls but increased t1/2 values in the patient group. This effect just reached statistical significance only when calculated by the power exponential method (P=0.05 but not by the linear component model. CONCLUSIONS: Delayed gastric emptying is not an invariable characteristic of symptomatic diabetic gastropathy. Clonidine, given as a single dose of 0.3 mg orally, has no gastric prokinetic effects. It may act on gastric afferent innervation or, more likely, at a central site to reduce nausea and vomiting. The analysis of gastric emptying data by the power exponential and the two linear component methods yields equivalent results.


Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Clonidina/farmacología , Vaciamiento Gástrico/efectos de los fármacos , Administración Oral , Adulto , Estudios de Casos y Controles , Complicaciones de la Diabetes , Método Doble Ciego , Femenino , Gastroparesia/etiología , Humanos , Masculino , Persona de Mediana Edad
4.
Nucl Med Commun ; 23(1): 13-8, 2002 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11748433

RESUMEN

Single photon emission computerized tomography (SPECT) studies were performed on 34 manifest Huntington's disease (HD) patients at various stages of clinical pathology ranging from early chorea to late dystonia with or without signs of dementia and 12 pre-symptomatic patients with abnormal terminal CAG expansions. Thirty HD patients with obvious clinical signs and seven pre-symptomatic patients without signs or symptoms of HD displayed selective caudate hypoperfusion by direct visual inspection. Such qualitative, selective striatal hypoperfusion patterns can be indicative of early and persistent metabolic changes in striatal neuropathology. SPECT studies can be useful in documenting early pre-clinical changes in patients with abnormal terminal CAG expansions and in confirming the presence of caudate pathology in patients with clinical signs of HD.


Asunto(s)
Enfermedad de Huntington/diagnóstico por imagen , Degeneración Nerviosa/diagnóstico por imagen , Adulto , Anciano , ADN/genética , Femenino , Humanos , Enfermedad de Huntington/genética , Masculino , Persona de Mediana Edad , Degeneración Nerviosa/genética , Radiofármacos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tomografía Computarizada de Emisión de Fotón Único
6.
J Acoust Soc Am ; 109(5 Pt 1): 2098-102, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11386561

RESUMEN

A comparison is made between the variation of delta Ljnd with L (loudness), based on the beat-detection data of Riesz at 1 kHz [Phys. Rev. 31, 867-875 (1928)], and analogous relations obtained from a cross section of studies. Data analysis shows that only beat detection exhibits the degree of level-dependent variation in slope relating log (delta Ljnd) to log (L) described in a recent paper by Allen and Neely [J. Acoust. Soc. Am. 102, 3628-3646 (1997)]. Moreover, the slope variation determined from beat detection is not dependent on the detailed shape of the loudness function. The results imply that Allen and Neely's strong conclusions about the dependence of delta Ljnd on L are too tightly coupled to Riesz's methodology to be generally applicable.


Asunto(s)
Percepción Sonora/fisiología , Modelos Neurológicos , Audiometría , Humanos
7.
J Am Coll Cardiol ; 36(4): 1265-73, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11028482

RESUMEN

OBJECTIVES: We sought to compare dobutamine-atropine stress echocardiography (DASE) and dipyridamole Technetium 99-m (Tc-99m) sestamibi single photon emission computed tomography (SPECT) scintigraphy (DMIBI) for detecting coronary artery disease (CAD). BACKGROUND: Both DASE and DMIBI are effective for evaluating patients for CAD, but their concordance and limitations have not been directly compared. METHODS: To investigate these aims, patients underwent multistage DASE, DMIBI and coronary angiography within three months. Dobutamine-atropine stress echocardiography and stress-rest DMIBI were performed according to standard techniques and analyzed for their accuracy in predicting the extent of CAD. Segments were assigned to vascular territories according to standard models. Angiography was performed using the Judkin's technique. RESULTS: The 183 patients (mean age: 60 +/- 11 years, including 50 women) consisted of 64 patients with no coronary disease and 61 with single-, 40 with two- and 18 with three-vessel coronary disease. Dobutamine-atropine stress echocardiography and DMIBI were similarly sensitive (87%, 104/119 and 80%, 95/119, respectively) for the detection of CAD, but DASE was more specific (91%, 58/64 vs. 73%, 47/64, p < 0.01). Sensitivity was similar for the detection of CAD in patients with single-vessel disease (84%, 51/61 vs. 74%, 45/61, respectively) and multivessel disease (91%, 53/58 vs. 86%, 50/58, respectively). Multiple wall motion abnormalities and perfusion defects were similarly sensitive for multivessel disease (72%, 42/58 vs. 66%, 38/53, respectively), but, again, DASE was more specific than DMIBI (95%, 119/125 vs. 76%, 95/125, respectively, p < 0.01). Dobutamine-atropine stress echocardiography and DMIBI were moderately concordant for the detection and extent of CAD (Kappa 0.47, p < 0.0001) but were only fairly (Kappa 0.35, p < 0.001) concordant for the type of abnormalities (normal, fixed, ischemia or mixed). CONCLUSIONS: Dobutamine-atropine stress echocardiography and DMIBI were comparable tests for the detection of CAD. Both were very sensitive for the detection of CAD and moderately sensitive for the extent of disease. The only advantage of DASE was greater specificity, especially for multivessel disease. Dobutamine-atropine stress echocardiography may be advantageous in patients with lower probabilities of CAD.


Asunto(s)
Atropina , Enfermedad Coronaria/diagnóstico , Dobutamina , Ecocardiografía/métodos , Tecnecio Tc 99m Sestamibi , Tomografía Computarizada de Emisión de Fotón Único , Atropina/administración & dosificación , Cardiotónicos/administración & dosificación , Angiografía Coronaria , Diagnóstico Diferencial , Dobutamina/administración & dosificación , Prueba de Esfuerzo , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Parasimpatolíticos/administración & dosificación , Radiofármacos/administración & dosificación , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Tecnecio Tc 99m Sestamibi/administración & dosificación
8.
Clin Neuropathol ; 19(5): 230-4, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11048748

RESUMEN

BACKGROUND: The ability to predict treatment responsiveness and survival of patients with glioblastoma multiforme, the most malignant and most common primary brain tumor, would be a valuable asset. Tumor and proliferation markers such as p53 and PCNA have been immunohistochemically defined and have been useful in other tumors in determining prognosis. Therefore, the authors studied the correlation of responsiveness to treatment, time to progression and survival with p53 and PCNA labeling indices in a pre-irradiation chemotherapy study of the glioblastoma multiforme. METHODS: Immunohistopathology for labeling indices for p53 and PCNA using formalin-fixed, paraffin-embedded tissue from the glioblastomas of 23 patients entered into a phase II ECOG trial of pre-irradiation chemotherapy were defined using the streptavidin-peroxidase technique with AEC chromogen. The labeling indices were correlated with response to treatment time to progression and overall survival. Most patients received three cycles of BCNU for three days over three months and cisplatin monthly for three days over three months prior to external beam irradiation. RESULTS: There were no significant differences in treatment response, time to progression or overall survival in glioblastoma, patients with positive p53 labeling index (> 5%) versus a negative p53 labeling index (< or = 5%) or positive PCNA labeling (> 10%) versus a negative labeling index (< or = 10%) or any combination of P53 and PCNA labeling indices. CONCLUSIONS: Using this protocol of pre-irradiation chemotherapy, p53 and PCNA labeling indices in the glioblastoma multiforme did not predict treatment benefit.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/mortalidad , Glioblastoma/tratamiento farmacológico , Glioblastoma/mortalidad , Antígeno Nuclear de Célula en Proliferación/análisis , Proteína p53 Supresora de Tumor/análisis , Adulto , Anciano , Antineoplásicos/administración & dosificación , Biomarcadores de Tumor , Neoplasias Encefálicas/patología , Progresión de la Enfermedad , Femenino , Glioblastoma/patología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Radioterapia , Tasa de Supervivencia
9.
J Neurooncol ; 47(2): 145-52, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10982156

RESUMEN

Recent publications support the use of preradiation chemotherapy in the treatment of selected primary brain tumors. In the pediatric population, this treatment strategy often delays radiotherapy and may improve the outcome in patients. This manuscript describes the use of a preradiation chemotherapy approach for adult patients with newly diagnosed glioblastoma multiforme. The main objective of this trial was to determine the feasibility of delivering up to 3 monthly cycles of a 72 h continuous simultaneous intravenous infusion of BCNU (40 mg/m2/day) and cisplatin (40 mg/m2/day). Patients were evaluated for tumor response or progression after each cycle. Following the completion of the chemotherapy treatments or evidence of tumor progression, patients underwent external beam radiotherapy. A dose of 45 Gy was delivered to the pretreatment tumor volume plus surrounding edema and a margin of 3.0 cm. An additional 14.4 Gy was delivered to the preoperative volume plus a 2 cm margin. Fifty patients were enrolled, 47 were eligible and analyzable. Overall, 79% of patients were able to complete at least 2 cycles of treatment, exceeding the predefined measure of feasibility. One patient achieved a complete response, 10 patients a partial response and 18 patients had stable disease at completion of the chemotherapy treatments. Twenty-four patients experienced grade 4 toxicity, mostly hematologic. All patients were able to undergo radiotherapy following chemotherapy. These results indicate that a preradiation strategy is feasible. Although responses to the chemotherapy were seen, a phase III trial is needed to determine whether this approach provides an advantage over standard treatment; such a phase III trial has been undertaken by ECOG.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Adulto , Anciano , Neoplasias Encefálicas/radioterapia , Quimioterapia Adyuvante , Protocolos Clínicos , Estudios de Factibilidad , Femenino , Glioblastoma/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Radioterapia/métodos , Inducción de Remisión , Análisis de Supervivencia
10.
Nucl Med Commun ; 20(11): 1055-8, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10572916

RESUMEN

We studied the biodistribution and tumour localization of 99Tcm-labelled-5-thio-D-glucose (99Tcm-TG). 5-Thio-D-glucose was labelled with 99Tcm by direct stannous ion reduction. The biodistribution of 99Tcm-TG was investigated in normal rabbits and in mice bearing experimental tumours. In rabbits, the plasma and clearance of 99Tcm-TG was 14.5 +/- 2.0 and 11.3 +/- 3.0 ml.min-1 respectively. Urinary excretion at 1 h was 53 +/- 5%. 99Tcm-TG was injected intravenously in mice bearing MC26 colon carcinoma and tissue samples were analysed by gamma scintillation counting at various times. Uptake of 99Tcm-TG in tumour at 1 and 3 h was 1.6 +/- 0.3% and 1.2 +/- 0.3%; the tumour to muscle ratios were 2.7:1 and 4:1 respectively. The autoradiographic biodistribution of 99Tcm-TG in MX-1 human breast xenografted nude mice showed more persistent tumour uptake of 99Tcm-TG than 14C-2-deoxyglucose (14C-DG). 99Tcm-TG accumulated in the centre of the tumours; 14C-DG was decreased in this central region probably because of zones of infarction on necrosis. The discordance between the tumour uptake of 99Tcm-TG and 14C-DG indicates that 99Tcm-TG does not act like a glucose analog, suggesting 99Tcm-TG avidity for zones of infarction or necrosis. The further study of 99Tcm-TG in tumours and ischaemic injury is warranted.


Asunto(s)
Glucosa/análogos & derivados , Compuestos de Organotecnecio/farmacocinética , Radiofármacos/farmacocinética , Animales , Antimetabolitos , Autorradiografía , Neoplasias de la Mama/diagnóstico por imagen , Desoxiglucosa , Glucosa/farmacocinética , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Desnudos , Trasplante de Neoplasias/diagnóstico por imagen , Neoplasias Experimentales/diagnóstico por imagen , Conejos , Cintigrafía , Distribución Tisular , Trasplante Heterólogo
11.
Mayo Clin Proc ; 74(9): 897-9, 1999 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10488792

RESUMEN

Cardiac valvular involvement associated with Wegener granulomatosis is uncommon. We describe a 17-year-old male adolescent who sought medical attention because of a sore throat, arthralgias, low-grade fever, and fatigue of 3 weeks' duration. A rash was noted on his elbows, hands, and ankles; subsequently, a crusting lesion was noted in his internal nares, and infiltrates were detected on chest radiography. Blood cultures were negative for pathogens. An echocardiogram disclosed mild left ventricular enlargement with grade 2 aortic insufficiency, and Wegener granulomatosis was diagnosed based on an antineutrophil cytoplasmic antibody titer of 1:512. When blood cultures are negative for aortic valve endocarditis, a high index of clinical suspicion and antineutrophil cytoplasmic antibody testing may lead to the diagnosis of acute aortic insufficiency associated with Wegener granulomatosis.


Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/sangre , Insuficiencia de la Válvula Aórtica/etiología , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/diagnóstico , Enfermedad Aguda , Adolescente , Insuficiencia de la Válvula Aórtica/inmunología , Diagnóstico Diferencial , Granulomatosis con Poliangitis/inmunología , Humanos , Masculino
12.
Mol Biol Cell ; 10(7): 2209-19, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10397760

RESUMEN

The immunoglobulin (Ig) molecule is composed of two identical heavy chains and two identical light chains (H2L2). Transport of this heteromeric complex is dependent on the correct assembly of the component parts, which is controlled, in part, by the association of incompletely assembled Ig heavy chains with the endoplasmic reticulum (ER) chaperone, BiP. Although other heavy chain-constant domains interact transiently with BiP, in the absence of light chain synthesis, BiP binds stably to the first constant domain (CH1) of the heavy chain, causing it to be retained in the ER. Using a simplified two-domain Ig heavy chain (VH-CH1), we have determined why BiP remains bound to free heavy chains and how light chains facilitate their transport. We found that in the absence of light chain expression, the CH1 domain neither folds nor forms its intradomain disulfide bond and therefore remains a substrate for BiP. In vivo, light chains are required to facilitate both the folding of the CH1 domain and the release of BiP. In contrast, the addition of ATP to isolated BiP-heavy chain complexes in vitro causes the release of BiP and allows the CH1 domain to fold in the absence of light chains. Therefore, light chains are not intrinsically essential for CH1 domain folding, but play a critical role in removing BiP from the CH1 domain, thereby allowing it to fold and Ig assembly to proceed. These data suggest that the assembly of multimeric protein complexes in the ER is not strictly dependent on the proper folding of individual subunits; rather, assembly can drive the complete folding of protein subunits.


Asunto(s)
Proteínas Portadoras/metabolismo , Proteínas de Choque Térmico , Cadenas Pesadas de Inmunoglobulina/química , Cadenas Pesadas de Inmunoglobulina/metabolismo , Cadenas Ligeras de Inmunoglobulina/metabolismo , Chaperonas Moleculares/metabolismo , Animales , Sitios de Unión , Células COS/metabolismo , Retículo Endoplásmico , Chaperón BiP del Retículo Endoplásmico , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas Ligeras de Inmunoglobulina/química , Ratones , Pliegue de Proteína , Receptores de IgG/química , Receptores de IgG/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
13.
Ear Hear ; 20(3): 193-213, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10386847

RESUMEN

OBJECTIVE: The main goal of this study was to establish the viability of cross-modality matching (CMM) for the measurement of individual loudness functions in sensorineural-impaired hearing. To achieve this goal, CMM was tested rigorously to assess four measurement requirements: 1) internal consistency; 2) small relative variance across listeners; 3) test-retest reliability; and 4) data validity. DESIGN: The measurements involved two sensory continua: perceived length and loudness. Sensation-magnitude functions were generated for all listeners from absolute magnitude estimation (AME) of perceived length, from CMM between loudness and perceived length, and from AME and absolute magnitude production (AMP) of loudness. A total of 211 listeners, 83 with normal hearing at the stimulus frequency and 128 with a diagnosis of cochlear impairment of long duration, performed all four magnitude-scaling tasks. Supplementary loudness matches also were obtained. RESULTS: Based on the analysis of data, the following results were obtained. First, in accord with loudness measures in normal hearing, loudness measures in cochlear-impaired hearing showed that individuals with bilateral impairments can produce internally consistent loudness data. Second, over the stimulus range where cochlear impairment steepens the loudness function, in a log-log plot loudness slopes derived from CMM, like those obtained from AME and AMP of loudness, were larger in cochlear-impaired hearing than in normal hearing. However, the results of CMM were typically less variable than those obtained from AME and AMP of loudness, permitting a clear-cut distinction between loudness growth rates (slopes) in normal and cochlear-impaired hearing. Third, the results showed that within a cochlear-impaired population, much of the intersubject variability of the slope of the loudness function can be ascribed to the heterogeneity of individual thresholds. Consistent with loudness matching, the size of the slopes increased with the degree of hearing loss. The dependence of the size of the slopes on the degree of hearing loss was observed for hearing losses as large as 75 dB. Fourth, test-retest reliability data for 36 listeners showed that CMM can yield reliable and stable loudness-growth measures in cochlear-impaired hearing over the long term. Finally, equal-sensation matches obtained directly from loudness matching closely agreed with those obtained indirectly from magnitude scaling, indicating that CMM is a valid method for the measurement of loudness magnitudes. CONCLUSIONS: Taken together, the results demonstrate that CMM can yield stable, accurate, and robust loudness growth measures in cochlear-impaired hearing. Given its apparent reliability, validity, and ease of application, CMM has the potential to become a powerful tool for assessing the growth of loudness in a clinical population. Loudness-level functions derived from CMM may well be important for determining the frequency-gain response of a hearing aid that most closely compensates for the distorted input-output function of the impaired auditory system.


Asunto(s)
Pérdida Auditiva Sensorineural/diagnóstico , Pruebas Auditivas/instrumentación , Percepción Sonora/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Umbral Auditivo/fisiología , Cóclea/fisiopatología , Diseño de Equipo , Femenino , Pérdida Auditiva Sensorineural/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad
14.
J Cell Biol ; 144(1): 21-30, 1999 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-9885241

RESUMEN

Immunoglobulin heavy chain-binding protein (BiP) is a member of the hsp70 family of chaperones and one of the most abundant proteins in the ER lumen. It is known to interact transiently with many nascent proteins as they enter the ER and more stably with protein subunits produced in stoichiometric excess or with mutant proteins. However, there also exists a large number of secretory pathway proteins that do not apparently interact with BiP. To begin to understand what controls the likelihood that a nascent protein entering the ER will associate with BiP, we have examined the in vivo folding of a murine lambdaI immunoglobulin (Ig) light chain (LC). This LC is composed of two Ig domains that can fold independent of the other and that each possess multiple potential BiP-binding sequences. To detect BiP binding to the LC during folding, we used BiP ATPase mutants, which bind irreversibly to proteins, as "kinetic traps." Although both the wild-type and mutant BiP clearly associated with the unoxidized variable region domain, we were unable to detect binding of either BiP protein to the constant region domain. A combination of in vivo and in vitro folding studies revealed that the constant domain folds rapidly and stably even in the absence of an intradomain disulfide bond. Thus, the simple presence of a BiP-binding site on a nascent chain does not ensure that BiP will bind and play a role in its folding. Instead, it appears that the rate and stability of protein folding determines whether or not a particular site is recognized, with BiP preferentially binding to proteins that fold slowly or somewhat unstably.


Asunto(s)
Proteínas Portadoras/metabolismo , Proteínas de Choque Térmico/metabolismo , Cadenas Pesadas de Inmunoglobulina/metabolismo , Cadenas lambda de Inmunoglobulina/metabolismo , Chaperonas Moleculares/metabolismo , Pliegue de Proteína , Adenosina Trifosfatasas/genética , Animales , Sitios de Unión , Células COS , Proteínas Portadoras/genética , Cisteína , Disulfuros , Retículo Endoplásmico , Chaperón BiP del Retículo Endoplásmico , Proteínas de Choque Térmico/genética , Regiones Constantes de Inmunoglobulina , Región Variable de Inmunoglobulina , Cadenas lambda de Inmunoglobulina/biosíntesis , Chaperonas Moleculares/genética , Mutación , Células Tumorales Cultivadas
15.
J Neurooncol ; 37(1): 55-62, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9525838

RESUMEN

This study is a combined modality Phase II therapeutic trial to determine the efficacy of the novel combination of VP-16, Vincristine and Procarbazine in addition to postoperative radiation therapy in patients with high grade intracranial gliomas. Thirty three patients (median age 51 years) were entered (27 with glioblastoma multiforme, 6 with anaplastic astrocytoma). Toxicity was manageable with no lethal toxicities. Five of seven life threatening toxicities were hematologic. Median overall survival was 14.2 months. These data suggest this regimen is effective treatment for patients with high grade gliomas.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Glioma/tratamiento farmacológico , Glioma/radioterapia , Administración Oral , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Astrocitoma/tratamiento farmacológico , Astrocitoma/radioterapia , Terapia Combinada , Etopósido/administración & dosificación , Femenino , Glioblastoma/tratamiento farmacológico , Glioblastoma/radioterapia , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Procarbazina/administración & dosificación , Pronóstico , Análisis de Supervivencia , Vincristina/administración & dosificación
16.
Nucl Med Commun ; 19(1): 13-21, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9515543

RESUMEN

Among adults, low back pain (LBP) persisting for more than 3 months is a common complaint. A variety of imaging modalities including bone scintigraphy have been recommended as appropriate for the investigation of chronic LBP, even when there is no reason to suspect that the pain is due to tumour, infection or inflammatory arthritis. In this chronic LBP population, the diagnostic benefit of bone SPET, together with planar flow study, blood pool and delayed three-phase imaging, was assessed, Altogether, 2108 consecutive adult patients were entered into the chronic LBP bone scintigraphy database. Retrospective exclusion of patients with a history of tumour, infection or inflammatory arthritis reduced the population to 1390, of whom 916 underwent a lumbosacral spine flow study and blood pool imaging in addition to planar and SPET bone scintigraphy. The diagnostic benefit of these imaging studies was tabulated and compared. In addition, a retrospective chart review of the patients with renal and other soft tissue abnormalities identified by a flow study and blood pool imaging was undertaken with a view to documenting any changes in treatment planning over the 6 months following the nuclear medicine studies. Of the lumbosacral spine abnormalities, 44.1% were seen equally well on planar and SPET images, 24.0% better on SPET, 31.4% only seen on SPET, and 0.4% only seen on planar imaging. The distribution of abnormalities identified on SPET images in the lumbar spine was divided between vertebral bodies (36.1%), lamina or pedicles (which included frequent sites of increased uptake in the articular facets and pars interarticularis) (53.8%), spinous processes (8.7%) and transverse processes (1.3%). For the flow study and blood pool imaging, there was a 16.7% rate of positive studies. However, there were no documented changes in treatment planning because of these positive findings. In conclusion, when used to examine adult patients with chronic LBP, SPET detects significantly more scintigraphic abnormalities than planar imaging. The addition of a flow study and blood pool imaging as part of these LBP examinations results in a significant benefit. However, the clinical utility of such flow study and blood pool imaging studies cannot be confirmed.


Asunto(s)
Dolor de Espalda/diagnóstico , Huesos/diagnóstico por imagen , Imagen Eco-Planar , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/patología , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Anciano , Anciano de 80 o más Años , Dolor de Espalda/diagnóstico por imagen , Dolor de Espalda/etiología , Huesos/patología , Bases de Datos como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad
17.
Clin Nucl Med ; 23(2): 77-82, 1998 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9481493

RESUMEN

The diagnostic efficacy of (1) combined three-phase bone scintigraphy and In-111 labeled WBC scintigraphy (Bone/WBC), (2) MRI, and (3) conventional radiography in detecting osteomyelitis of the neuropathic foot was compared. Conventional radiography was comparable to MRI for detection of osteomyelitis. MRI best depicted the presence of osteomyelitis in the forefoot. Particularly in the setting of Charcot joints, Bone/WBC was more specific than conventional radiography or MRI.


Asunto(s)
Artropatía Neurógena/complicaciones , Neuropatías Diabéticas/complicaciones , Enfermedades del Pie/diagnóstico , Osteomielitis/diagnóstico , Adulto , Anciano , Pie Diabético/complicaciones , Femenino , Pie/diagnóstico por imagen , Pie/patología , Enfermedades del Pie/diagnóstico por imagen , Humanos , Radioisótopos de Indio , Leucocitos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Osteomielitis/complicaciones , Osteomielitis/diagnóstico por imagen , Curva ROC , Radiografía , Cintigrafía , Sensibilidad y Especificidad
18.
J Palliat Med ; 1(3): 277-83, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-15859838

RESUMEN

Beta-emitting, bone-seeking radiopharmaceuticals, administered systemically, represent a good alternative or adjuvant to external beam radiotherapy for palliation of painful osteoblastic bone metastases. The most frequently used radiopharmaceutical for this purpose is strontium 89, followed by samarium 153 ethylenediaminetetramethylene phosphonate, and infrequently phosphorus 32 orthophosphate. Prior to consideration for radionuclide therapy, recent bone scans should be evaluated in order to determine if the patient has painful osteoblastic lesions likely to respond to therapy. Approximately 70% of patients with prostate and breast cancer will have a reduction in pain in response to radionuclide therapy, beginning within 2 to 4 weeks and lasting between 2 and 6 months. Patients who are expected to live 3 or more months are more likely to benefit than patients with shorter duration life expectancy. Hematosuppression is the chief side effect of radionuclide therapy, with leukopenia and thrombocytopenia more likely to be clinically significant than anemia. Relative contraindications for treatment include osteolytic lesions, pending spinal cord compression or pathologic fracture, preexisting severe myelosuppression, urinary incontinence, inability to follow radiation safety precautions, and severe renal insufficiency.

19.
Am Heart J ; 134(5 Pt 1): 822-34, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9398094

RESUMEN

To directly compare dobutamine echocardiography and resting single photon emission computed tomographic (SPECT) thallium-201 (Tl-201) scintigraphy for the detection of reversible dysfunction, 64 patients underwent dobutomine echocardiography (baseline, low dose 5 and 10 mg/kg/min, and peak dose), rest Tl-201 scintigraphy (3 mCi - 15 minute and 3- to 4-hour SPECT imaging), and coronary angiography during the first week after acute myocardial infarction. Follow-up echocardiography was performed 4 to 8 weeks after discharge. Wall thickening improved at follow-up in 52% (207 of 399) of the dysfunctional segments. By receiver operating characteristic analysis, biphasic responses and sustained improvement during dobutamine echocardiography were more accurate (p < 0.01) than Tl-201 uptake by SPECT scintigraphy for reversible dysfunction. The greater accuracy of dobutamine echocardiography resulted from higher accuracy in akinetic segments, Q wave infarction, and multivessel coronary artery disease. In conclusion, dobutamine echocardiography was more accurate than resting SPECT Tl-201 scintigraphy for reversible dysfunction after acute myocardial infarction.


Asunto(s)
Cardiotónicos , Dobutamina , Infarto del Miocardio/diagnóstico por imagen , Radioisótopos de Talio , Tomografía Computarizada de Emisión de Fotón Único , Antagonistas Adrenérgicos beta/uso terapéutico , Anciano , Angiografía Coronaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/tratamiento farmacológico , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Curva ROC , Terapia Trombolítica , Ultrasonografía
20.
J Psychosom Res ; 43(2): 143-57, 1997 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9278904

RESUMEN

Fifty-six women with stage II breast cancer receiving adjuvant chemotherapy were recruited for a study evaluating and comparing coping patterns for differences in physical and psychological side effects during treatment with adjuvant chemotherapy. Cluster analyses were used to split women into confrontive, avoidant-confrontive, avoidant-resigned, and resigned coping clusters. Side-effect measurements were taken on the day of adjuvant chemotherapy infusion and 3 and 7 days later. Repeated measures ANCOVAs indicated that coping clusters predicted significant variance in physical, psychological, and total side effects when variance in covariates was held constant. Confrontive subjects reported significantly fewer psychological and physical symptoms than avoidant-confrontive and avoidant-resigned copers. Confrontive copers also reported fewer side effects than resigned copers, but this difference was not significant when differences in covariate distributions were controlled. Particularly robust differences were noted when confrontive copers were compared with avoidant-confrontive copers. Results suggest that a critical component in optimal coping may be a willingness to discuss and think about illness.


Asunto(s)
Adaptación Psicológica , Actitud Frente a la Salud , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/psicología , Adulto , Anciano , Análisis de Varianza , Asertividad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/efectos adversos , Quimioterapia Adyuvante/psicología , Análisis por Conglomerados , Estudios Transversales , Reacción de Fuga , Femenino , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Estadificación de Neoplasias/psicología , Participación del Paciente , Muestreo , Apoyo Social , Factores Socioeconómicos , Factores de Tiempo
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