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1.
Langmuir ; 27(22): 13897-903, 2011 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-22011196

RESUMO

The impact of picoliter-sized water droplets on superhydrophobic CF(4) plasma fluorinated polybutadiene surfaces is investigated with high-speed imaging. Variation of the surface topography by plasmachemical modification enables the dynamics of wetting to be precisely controlled. Final spreading ratios as low as 0.63 can be achieved. A comparison of the maximum spreading ratio and droplet oscillation frequencies to models described in the literature shows that both are found to be much lower than theoretically predicted.

2.
Cancer Res ; 57(23): 5221-5, 1997 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-9393738

RESUMO

A candidate tumor suppressor gene, MMAC1/PTEN, located in human chromosome band 10q23, was recently identified based on sequence alterations observed in several glioma, breast, prostate, and kidney tumor specimens or cell lines. To further investigate the mutational profile of this gene in human cancers, we examined a large set of human tumor specimens and cancer cell lines of many types for 10q23 allelic losses and MMAC1 sequence alterations. Loss of heterozygosity (LOH) at the MMAC1 locus was observed in approximately one-half of the samples examined, consistent with the high frequency of 10q allelic loss reported for many cancers. Of 124 tumor specimens exhibiting LOH that have been screened for MMAC1 alterations to date, we have detected variants in 13 (approximately 10%) of these primary tumors; the highest frequency of variants was found in glioblastoma specimens (approximately 23%). Novel alterations identified in this gene include a missense variant in a melanoma sample and a splicing variant and a nonsense mutation in pediatric glioblastomas. Of 76 tumor cell lines prescreened for probable LOH, microsequence alterations of MMAC1 were detected in 12 (approximately 16%) of the lines, including those derived from astrocytoma, leukemia, and melanoma tumors, as well as bladder, breast, lung, prostate, submaxillary gland, and testis carcinomas. In addition, in this set of tumor cell lines, we detected 11 (approximately 14%) homozygous deletions that eliminated coding portions of MMAC1, a class of abnormality not detected by our methods in primary tumors. These data support the occurrence of inactivating MMAC1 alterations in multiple human cancer types. In addition, we report the discovery of a putative pseudogene of MMAC1 localized on chromosome 9.


Assuntos
Cromossomos Humanos Par 10 , Mutação , Neoplasias/genética , Monoéster Fosfórico Hidrolases , Proteínas Tirosina Fosfatases/genética , Proteínas Supressoras de Tumor , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Criança , Mapeamento Cromossômico , Éxons , Feminino , Deleção de Genes , Marcadores Genéticos , Variação Genética , Glioblastoma/genética , Glioblastoma/patologia , Glioma/genética , Glioma/patologia , Humanos , Íntrons , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Neoplasias/patologia , PTEN Fosfo-Hidrolase , Mutação Puntual , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Tirosina Fosfatases/análise , Proteínas Tirosina Fosfatases/biossíntese , Deleção de Sequência , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia , Células Tumorais Cultivadas
3.
Oncogene ; 18(9): 1765-9, 1999 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-10208437

RESUMO

PTEN/MMAC1 is a recently characterized tumor suppressor. A pseudogene derived from the human PTEN/MMAC1 phosphatase, psiPTEN, has been reported. Recent analysis of the pseudogene revealed conflicting results about the expression of psiPTEN. In this study, we show that the PTEN/MMAC1 pseudogene is actively transcribed in all cells and tissues examined. In some cases, pseudogene transcripts were found to represent as much as 70% of the total PTEN/MMAC1 RNA. As psiPTEN is transcribed, there is a potential for misinterpretation of PTEN/MMAC1 mutations when RT-PCR techniques are used, as well as potential for a psiPTEN-encoded translation product. Although we were unable to detect a pseudogene protein product in the cell lines examined, a baculovirus produced GST pseudogene fusion protein exhibited phosphatase activity comparable to wild type. The results of this study, taken together, indicate the potential complication of PTEN/MMAC1 molecular analysis caused by the expression of psiPTEN.


Assuntos
Genes Supressores de Tumor , Monoéster Fosfórico Hidrolases/genética , Pseudogenes , Transcrição Gênica , Proteínas Supressoras de Tumor , Sequência de Aminoácidos , Sequência de Bases , DNA Complementar , Expressão Gênica , Humanos , Dados de Sequência Molecular , PTEN Fosfo-Hidrolase , Monoéster Fosfórico Hidrolases/metabolismo , Células Tumorais Cultivadas
4.
Oncogene ; 18(6): 1261-6, 1999 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-10022807

RESUMO

MMAC1, also known as PTEN or TEP-1, was recently identified as a gene commonly mutated in a variety of human neoplasias. Sequence analysis revealed that MMAC1 harbored sequences similar to those found in several protein phosphatases. Subsequent studies demonstrated that MMAC1 possessed in vitro enzymatic activity similar to that exhibited by dual specificity phosphatases. To characterize the potential cellular functions of MMAC1, we expressed wild-type and several mutant variants of MMAC1 in the human glioma cell line, U373, that lacks endogenous expression. While expression of wild-type MMAC1 in these cells significantly reduced their growth rate and saturation density, expression of enzymatically inactive MMAC1 significantly enhanced growth in soft agar. Our observations indicate that while wild-type MMAC1 exhibits activities compatible with its proposed role as a tumor suppressor, cellular expression of MMAC1 containing mutations in the catalytic domain may yield protein products that enhance transformation characteristics.


Assuntos
Genes Supressores de Tumor , Glioma/genética , Monoéster Fosfórico Hidrolases/biossíntese , Proteínas Supressoras de Tumor , Domínio Catalítico/genética , Adesão Celular , Divisão Celular , Transformação Celular Neoplásica , Glioma/enzimologia , Humanos , Mutação , PTEN Fosfo-Hidrolase , Fenótipo , Monoéster Fosfórico Hidrolases/genética , Proteínas Recombinantes/biossíntese , Células Tumorais Cultivadas
5.
J Am Coll Cardiol ; 38(7): 1902-11, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11738292

RESUMO

OBJECTIVES: We surveyed the literature to estimate prediction values for five common tests for risk of major arrhythmic events (MAEs) after myocardial infarction. We then determined feasibility of a staged risk stratification using combinations of noninvasive tests, reserving an electrophysiologic study (EPS) as the final test. BACKGROUND: Improved approaches are needed for identifying those patients at highest risk for subsequent MAE and candidates for implantable cardioverter-defibrillators. METHODS: We located 44 reports for which values of MAE incidence and predictive accuracy could be inferred: signal-averaged electrocardiography; heart rate variability; severe ventricular arrhythmia on ambulatory electrocardiography; left ventricular ejection fraction; and EPS. A meta-analysis of reports used receiver-operating characteristic curves to estimate mean values for sensitivity and specificity for each test and 95% confidence limits. We then simulated a clinical situation in which risk was estimated by combining tests in three stages. RESULTS: Test sensitivities ranged from 42.8% to 62.4%; specificities from 77.4% to 85.8%. A three-stage stratification yielded a low-risk group (80.0% with a two-year MAE risk of 2.9%), a high-risk group (11.8% with a 41.4% risk) and an unstratified group (8.2% with an 8.9% risk equivalent to a two-year incidence of 7.9%). CONCLUSIONS: Sensitivities and specificities for the five tests were relatively similar. No one test was satisfactory alone for predicting risk. Combinations of tests in stages allowed us to stratify 91.8% of patients as either high-risk or low-risk. These data suggest that a large prospective study to develop a robust prediction model is feasible and desirable.


Assuntos
Infarto do Miocárdio/complicações , Taquicardia Ventricular/etiologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Eletrocardiografia Ambulatorial , Humanos , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Valor Preditivo dos Testes , Curva ROC , Medição de Risco , Processamento de Sinais Assistido por Computador , Volume Sistólico , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/terapia , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/fisiologia
6.
Exp Hematol ; 22(13): 1227-35, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7957709

RESUMO

In this report, we evaluated the short-term expansion of murine bone marrow mononuclear cells (BMMNC) and enriched stem cell populations to determine the capacity of these cells for long-term rescue and engraftment to lethally irradiated recipients. In our study, nonadherent bone marrow mononuclear cell (NBM-MNC) and Thy1+Lin- stem cells populations were cultured with interleukin-3 (IL-3) or IL-3 plus stem cell factor (SCF) for periods up to 6 days. By day 6 of culture, the mononuclear cells (MNC) decreased to 6% of input cell number, whereas Thy1+Lin- cells increased by 2310%. Doses of 95,000; 100,000; 50,000; and 250,000 NBM-MNCs at 0, 1, 2, and 6 days of culture, respectively, rescued 50% of lethally irradiated mice. When 250,000 MNCs were cultured for 0, 1, 2, and 6 days, 71, 61, 100, and 50% of the animals survived lethal irradiation for greater than 24 weeks. In contrast, doses of 8,000 and 21,000 Thy1+Lin- cells cultured 0 and 1 day, respectively, yielded 50% survival rates. These same cells cultured for 6 days failed to rescue recipients even at high doses. Twenty thousand Thy1+Lin- cells cultured for 0, 1, 2, and 6 days, even in the presence of SCF, produced decreasing survival rates of 86, 43, 26, and 0%, respectively. The proliferative responses of these different populations in combination with their long-term rescue abilities indicated that the absolute number of long-term rescue units (LD50, 24 weeks) in the cultured Thy1+Lin- population decreased faster than in similarly cultured NBM-MNCs. Studies evaluating donor cell engraftment demonstrated that animals rescued with cultured Thy1+Lin- and NBM-MNCs maintained high levels of donor reconstitution [7]. The percent donor T cell engraftment did not significantly change between 2 and 17 months post-bone marrow transplantation (post-BMT). Therefore, those animals who received sufficient cells to survive lethal irradiation generally established and maintained high levels of donor engraftment. The data suggest a role for accessory cells and/or factors in the preservation of stem cell activity.


Assuntos
Células da Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Animais , Separação Celular , Sobrevivência Celular , Células Cultivadas , Feminino , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Quimera por Radiação , Linfócitos T/citologia , Antígenos Thy-1/análise , Fatores de Tempo , Células Tumorais Cultivadas
7.
Hypertension ; 21(4): 504-9, 1993 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8458649

RESUMO

The Association for the Advancement of Medical Instrumentation develops voluntary standards for medical devices so that manufacturers might provide information on their product and basic safety and performance criteria that should be considered in qualifying the instrument for clinical use. American national standards are generated through a consensus process by committees consisting of experts in research, development, and design from user, industry, and government communities. Draft standards are made available for public review and may become American national standards after review by the American National Standards Institute. The first American national standard for electronic and automated sphygmomanometers was published in monograph form in 1987. The objective of the revised 1992 standard for electronic and automated sphygmomanometers is to provide updated labeling, safety, and performance requirements that help ensure that consumers and health care professionals are supplied with safe, accurate devices for the indirect measurement of blood pressure, including ambulatory blood pressure recorders. This standard permits validation of the automatic or electronic device by comparison with either direct, intra-arterial blood pressure measurements or the noninvasive cuff/stethoscope technique, based on Korotkoff sounds identified by individuals trained in auscultation. This summary report of the 1992 American national standard for automatic sphygmomanometers provides recommendations for the methods of comparison, statistical analysis of the data, presentation of the results, and criteria for acceptability. Users, researchers, and instrument designers should refer to the American national standard monograph for detailed requirements.


Assuntos
Monitores de Pressão Arterial/normas , Pressão Sanguínea , Autoanálise/normas , Humanos , Padrões de Referência , Estados Unidos
8.
Arch Neurol ; 52(2): 162-7, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7848125

RESUMO

OBJECTIVE: Toxicity and safety study of concurrent cisplatin therapy and iodine 125 (125I) brachytherapy. BACKGROUND: Iodine 125 brachytherapy has an established role in surgically accessible recurrent tumors of brain. Cisplatin has antitumoral activity against glial neoplasms and has demonstrated sensitization of tumor to radiotherapy. DESIGN/METHODS: In 16 patients (age range, 13 to 68 years, median, 47 years), stereotactically placed catheters were afterloaded with 125I sources. A median 50-Gy minimum treatment volume dose was delivered during a 100-hour period along with cisplatin (20 mg/m2 per day for 5 days). Histologic diagnoses included glioblastoma multiforme (n = 11), anaplastic astrocytoma (n = 3), ependymoma (n = 1), and anaplastic oligodendroglioma (n = 1). Tumor volumes ranged from 7.0 to 73 cm3 (median, 25 cm3). RESULTS: Early complications included headache (n = 7), transient exacerbations of preexisting neurologic deficits (n = 5), seizures (n = 3), and nausea/vomiting (n = 3). Late complications included steroid dependency (n = 10), progressive dementia in the absence of recurrent tumor (n = 1), and radiation-induced necrosis (n = 9) requiring reoperation (n = 9). Fifteen of 16 patients were assessable, with a median follow-up time of 9.5 months. Brachytherapy was discontinued in one patient owing to an acute subdural hematoma. A partial response was seen in five patients, disease remained stable in seven patients, and disease progressed in three patients. CONCLUSIONS: We conclude that 125I brachytherapy with concurrent cisplatin therapy is associated with an acceptable level of toxic effects and warrants further investigation.


Assuntos
Braquiterapia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Cisplatino/uso terapêutico , Glioma/tratamento farmacológico , Glioma/radioterapia , Radioisótopos do Iodo/uso terapêutico , Adolescente , Adulto , Idoso , Encéfalo/patologia , Neoplasias Encefálicas/psicologia , Feminino , Glioma/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Necrose , Recidiva Local de Neoplasia/tratamento farmacológico , Testes Neuropsicológicos , Lesões por Radiação
9.
Cancer Gene Ther ; 5(2): 92-100, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9570300

RESUMO

The use of genetically modified tumor cells as vaccines has been successful in numerous animal models of grafted syngenic tumors and has provided the groundwork for many clinical trials of gene therapy in cancer patients. To investigate the real efficacy of ex vivo gene therapy-based vaccines, we used transgenic mice that express the SV40 large T and small t antigens under the control of hepatic antithrombin III (ASV-B)-regulatory sequences. These mice systematically develop hepatocarcinoma. Hepatoma cells, derived from ASV-B transgenic mice, were gene-transduced to express either interleukin-2, interleukin-4, the granulocyte-macrophage colony-stimulating factor, or the T-cell costimulatory molecule B7.1. First, we demonstrated the vaccine potential of engineered hepatoma cells by immunizing nontransgenic mice with these cells, which prevented the growth of subsequent grafted nontransduced hepatoma cells. However, vaccination of pretumoral transgenic animals with various combinations of engineered hepatoma cells failed to inhibit hepatoma onset and progression. Rather, tumor development in ASV-B mice appears to be dependent on the immune system, since neonatal induction of immunotolerance to tumor in ASV-B mice cells was associated with a moderate, but significant, acceleration of tumor development. These results seriously call into question the efficacy of this strategy of active vaccinotherapy against natural tumors.


Assuntos
Vacinas Anticâncer/uso terapêutico , Neoplasias Experimentais/prevenção & controle , Transdução Genética , Animais , Antígenos Transformantes de Poliomavirus/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neoplasias Experimentais/genética
10.
Semin Radiat Oncol ; 9(2): 155-62, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10092707

RESUMO

Neovascular age-related macular degeneration is the most common cause of severe irreversible blindness in the Western world in people older than age 50. Laser photocoagulation is the only proven treatment for this disease; however, fewer than 20% of patients are eligible for this treatment because the majority of choroidal neovascularization membranes are not visible by ophthalmoscopy or angiography. In addition, many patients elect not to undergo this treatment because laser treatment of subfoveal neovascular membranes results in immediate and permanent central visual loss. Several treatments are under investigation, including external-beam radiation therapy. There are multiple publications of early trials using radiation therapy, but to date there is only one randomized published study. This article reviews these trials and summarizes the status of radiation therapy as a treatment for macular degeneration.


Assuntos
Degeneração Macular/radioterapia , Idoso , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Int J Radiat Oncol Biol Phys ; 33(1): 183-8, 1995 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-7642417

RESUMO

PURPOSE: Resectability, local control, and survival were evaluated in advanced stage nonsmall cell lung cancer treated with simultaneous chemoradiation therapy delivered in an accelerated, interrupted twice-a-day schedule. METHODS AND MATERIALS: Forty-seven consecutive patients with Stage IIIA or IIIB nonsmall cell lung cancer, consenting to participation in the study, received cisplatin, 30 mg/m2 for 3 days, etoposid, 80 mg/m2 for 3 days, and 5-fluorouracil, 900 mg/m2 for 4 days. Radiation therapy consisted of 2 Gy given twice a day for 5 days. Two weeks rest was planned between cycles. Patients were evaluated for resectability after the second cycle. Any patient with unresectable tumor received a third cycle of treatment. RESULTS: Forty-seven patients were evaluable for acute toxicity: eighteen (38%) required an extended rest period for esophagitis or low blood count; 3 (6%) had sepsis, of whom 1 (2%) expired. Three patients (6%) had multiple blood transfusions for low hemoglobin. Median follow-up is 23.6 months, with a range of 10-49 months. Nine patients (19%) failed locally; 15 (32%) had local and distant failure; 7 (15%) failed only at distant sites. Twelve patients (25.5%) are alive with no evidence of disease; 4 patients were lost to follow-up with disease. The 2-year actuarial survival is 49%, and the 4-year is 28.2%. CONCLUSION: Simultaneous chemoradiation is well tolerated with acceptable toxicity. The overall 2- and 4-year actuarial survival is somewhat better than that reported in the literature. Resectability in Stage IIIB patients was not increased with this regimen nor was any surgical specimen free of cancer. The 47% distant failure rate is not different from those reported by others.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Dosagem Radioterapêutica , Taxa de Sobrevida
12.
Int J Radiat Oncol Biol Phys ; 28(3): 719-22, 1994 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-8113117

RESUMO

PURPOSE: To evaluate absorbable mesh for the suturing of afterloading catheters in patients with tumors involving the chest wall. METHODS AND MATERIALS: Patients underwent thoracotomy and resection of tumor; a layer of absorbable mesh was then sutured to the tumor bed. Nylon flexiguide afterloading catheters were sutured into the mesh at about 1.5 cm distance from each other. A second layer of mesh was then sutured on top of the catheters. The chest wall was closed. Orthogonal radiographs and CT scans of the area of implants were done to verify catheter position in each patient on day 1 and on the last day of implant. Computer dosimetry by digitization of dummy sources was performed on each set of radiographs. The same seed for both sets of films was chosen as the origin of digitization. All seed coordinates were compared directly to offset for any rotation of the patient during the two sets of films. The distances were calculated from all seed positions to the origin, then tabulated and compared. RESULTS: The distances agreed within a few millimeters (7-8 mm). The differences may be attributed to the patient's breathing and to the localization uncertainty. The resulting dose alteration was negligible. CONCLUSION: This technique appears to provide adequate anchorage of catheters with resulting constant seed position and dose distribution in areas of scant tissues or in surgical beds of considerable size.


Assuntos
Braquiterapia/instrumentação , Cateterismo/métodos , Telas Cirúrgicas , Neoplasias Torácicas/radioterapia , Idoso , Braquiterapia/métodos , Cateterismo/instrumentação , Humanos , Masculino
13.
Int J Radiat Oncol Biol Phys ; 44(4): 887-90, 1999 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-10386646

RESUMO

PURPOSE: An evaluation of plaque-mounted diode-light transillumination (DLT) for localization of episcleral plaques beneath juxtapapillary tumors. METHODS AND MATERIALS: Two patients scheduled for radiotherapy for juxtapapillary melanomas were offered DLT as an additional method of ophthalmic plaque localization. Plaques were constructed by affixing 4 non-heat producing, light-emitting diodes with their apertures flush with the episcleral outer surface of the plaque's rim. Bio-implantable epoxy was used to encapsulate the electronic components. Then the plaques were loaded with 103Pd seeds. After the eye-plaques were sewn to the episclera covering the base of the intraocular tumors; the diode-lights were illuminated, viewed and recorded. Photodocumentation of the relative position of the 4 lights around tumor's base was obtained in both cases. RESULTS: Digital images of plaque-mounted diode retro-transillumination were obtained. No evidence of diode-light toxicity was noted. Both tumors were found to be covered by the ophthalmic plaques. CONCLUSION: Juxtapapillary tumors are often difficult or impossible to visualize with standard transillumination techniques and have been associated with poor local control rates. We have developed plaque-mounted DLT in an effort to improve ophthalmic plaque localization. Retrobulbar transillumination was viewed by indirect ophthalmoscopy and recorded with video-imaging. This technique provides unique photographic documentation of episcleral plaque localization beneath juxtapapillary tumors.


Assuntos
Neoplasias da Coroide/radioterapia , Melanoma/radioterapia , Transiluminação/métodos , Humanos , Transiluminação/instrumentação
14.
Int J Radiat Oncol Biol Phys ; 19(3): 569-75, 1990 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2211205

RESUMO

Between March 1982 and October 1987, 375 fields in 187 patients with AIDS-related Kaposi's Sarcoma were treated in the Department of Radiation Oncology at the University of California in San Francisco (UCSF). Field sizes ranging from 2 x 2 cm to total skin received doses of 8 Gy in a single fraction to 15-40 Gy in 5-10 fractions. Seventy-four percent of the patients have died. Response to treatment was achieved in over 90% of treated fields, with a median time to progression of 21 months and an actuarial freedom from relapse at 6 months of 69% (97 patients alive). There was no difference in outcome regardless of the fractionation regimen used. Severe reactions were noted in 17% of treated fields, but this incidence was significantly lower when a single fraction of 8 Gy was used (p less than 0.001). Radiation therapy plays an important palliative role in this devastating disease. This review supports the use of a single 8 Gy fraction for all Kaposi's Sarcoma lesions of the skin. Further data regarding single fraction therapy for lesions of other sites are needed.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Sarcoma de Kaposi/radioterapia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/radioterapia , Adulto , Neoplasias da Túnica Conjuntiva/epidemiologia , Neoplasias da Túnica Conjuntiva/etiologia , Neoplasias da Túnica Conjuntiva/radioterapia , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/etiologia , Neoplasias Gastrointestinais/radioterapia , Humanos , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/etiologia , Neoplasias Laríngeas/radioterapia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/etiologia , Neoplasias Orofaríngeas/radioterapia , Estudos Retrospectivos , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/etiologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/radioterapia , Análise de Sobrevida
15.
Int J Radiat Oncol Biol Phys ; 36(4): 861-5, 1996 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-8960514

RESUMO

PURPOSE: Neovascular macular degeneration is the leading cause of severe blindness in North America today. Limited treatments are available for this disease process. A Phase I/II study was performed to determine the toxicity and efficacy of external beam radiotherapy in patients with age-related subfoveal neovascularization. METHODS AND MATERIALS: Between March 1994 and June 1995, 52 patients with a mean age of 80 (60-92) were enrolled. These patients were either not eligible or were poor candidates for laser photocoagulation, primarily because of the subfoveal location of the neovascularization. Initial visual acuities ranged from 20 out of 32 to finger counting at 3 feet. All patients underwent fluorescein angiographic evaluation and documentation of their neovascular disease prior to irradiation. Patients were treated with a single lateral 4- or 6-MV photon beam, to a dose of 14-15 Gy in eight fractions over 10 days. The field size averaged 5 x 3 cm. RESULTS: No significant acute morbidity was noted. All patients underwent ophthalmic examinations and repeat angiography at 1 and 3 months posttreatment and then at 3-month intervals. With a mean follow-up of 7 months (3-18 months), 41 patients (79%) are within two lines of their pretreatment visual acuity. On angiographic imaging, there was stabilization of subfoveal neovascular membranes in 34 patients (65%). New neovascular membranes have been noted in five patients. CONCLUSIONS: It appears that radiotherapy can affect active subretinal neovascularization, but it is unlikely to prevent new neovascular events produced by this chronic disease. Further investigation is warranted.


Assuntos
Degeneração Macular/radioterapia , Neovascularização Patológica/radioterapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Acuidade Visual/efeitos da radiação
16.
Int J Radiat Oncol Biol Phys ; 15(3): 559-65, 1988 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3138208

RESUMO

Forty-five consecutive patients with chordoma or chondrosarcoma at the base of skull or cervical spine were treated at the University of California Lawrence Berkeley Laboratory (UCLBL) and University of California School of Medicine, San Francisco (UCSF) between November 1977 and October 1986. All patients had undergone a subtotal surgical resection. Twenty-three patients were treated definitively with charged particles, 13 patients were treated with photons and particles, and 9 patients were treated for recurrent disease. Total doses ranged from 36 to 80 Gray equivalent (GyE). Thirty-three patients are alive with a minimum followup of 1 year. The actuarial survival and local control for all patients at 5 years is 62% and 59%, respectively. Patients treated for primary disease had a 78% actuarial local control rate at 2 years, whereas the rate for patients with recurrent disease was 33%. Patients with smaller visible tumor volumes (less than 20 cc) had a significantly better local control rate than patients with larger tumor volumes (80% vs 33% actuarial rate at 5 years). Patients with chondrosarcoma had the highest local control rate, as did patients treated with particles alone. Complications included 3 patients with unilateral visual loss, two patients who became blind, and 4 patients with radiation injury to the brainstem.


Assuntos
Vértebras Cervicais , Condrossarcoma/radioterapia , Cordoma/radioterapia , Radioterapia de Alta Energia , Neoplasias Cranianas/radioterapia , Neoplasias da Coluna Vertebral/radioterapia , Análise Atuarial , Adulto , Condrossarcoma/mortalidade , Cordoma/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Dosagem Radioterapêutica , Neoplasias Cranianas/mortalidade , Neoplasias da Coluna Vertebral/mortalidade
17.
Int J Radiat Oncol Biol Phys ; 38(3): 601-5, 1997 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-9231685

RESUMO

PURPOSE: To catalogue the presenting symptoms of patients with AIDS who are presumed to have primary central nervous system lymphoma (PCNSL). To document the palliative efficacy of cranial irradiation (RT) relative to the endpoints of complete and overall response for the respective symptoms. METHODS: An analysis of 163 patients with AIDS-related PCNSL who were evaluated at nine urban hospitals was performed. These patients were treated for PCNSL after the establishment of a tissue diagnosis or on a presumptive basis after failing empiric treatment for toxoplasmosis. All patients were treated between 1983 and 1995 with radiotherapy (median dose-fractionation scheme = 3 Gy x 10) and steroids (>90% dexamethasone). Because multiple fractionation schemes were used, prescriptions were converted to biologically effective doses according to the formula, Gy10 = Total Dose x (1 + fractional dose/alpha-beta); using an alpha-beta value of 10. RESULTS: The overall palliative response rate for the entire group was 53%. In univariate analysis, trends were present associating complete response rates with higher performance status (KPS > or = 70 vs. KPS < or = 60 = 17% vs. 5%), female gender (women vs. men = 29% vs. 8%), and the delivery of higher biologically effective doses (BED) of RT (Gy10 > 39 vs. < or = 39 = 20% vs. 5%). In multivariate analysis of factors predicting complete response, both higher KPS and higher BED retained independent significance. A separate univariate analysis identified high performance status (KPS > or = 70 vs. KPS < or = 60 = 71% vs. 47%), and young age (< or = 35 vs. > 35 = 61% vs. 40%) as factors significantly correlating with the endpoint of the overall response. In multivariate analysis, high performance status and the delivery of higher biologically effective doses of irradiation correlated significantly with higher overall response rates. CONCLUSION: Most AIDS patients who develop symptoms from primary lymphoma of the brain can achieve some palliation from a management program that includes cranial irradiation. Young patients with excellent performance status are most likely to respond to treatment. The delivery of higher biologically effective doses of irradiation also may increase the probability of achieving a palliative response.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Irradiação Craniana , Linfoma Relacionado a AIDS/radioterapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Fatores de Risco , Abuso de Substâncias por Via Intravenosa/complicações
18.
Transplantation ; 63(2): 194-201, 1997 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-9020317

RESUMO

Free radical mediated lipid peroxidation (LPO) has been implicated in the pathogenesis of ischemic-reperfusion injury (IRI). To address the renoprotective effect(s) of LPO inhibition, the efficacy of the 21 aminosteroid U74389G was evaluated in three IRI models. In Model 1 51 unilateral nephrectomized rats that underwent 60 min of warm ischemia followed by a 72-hr reperfusion interval were treated with the test vehicle only, or 3, 6, or 12 mg/kg of U74389G intravenously, 5 min pre- or postischemia. In Model 2 Sprague-Dawley rats underwent sham operation (n=9), or 45 min of warm ischemia and 10 min of reperfusion with U74389G (6 mg/kg; n=10) or test vehicle only (n=10) administered intravenously over 10 min beginning 5 min prior to clamp release. After reperfusion, LPO was determined by assay of snap frozen tissue for thiobarbituric acid (TBA) concentrations (nmol/g tissue weight). In Model 3 domestic lean maid pigs (14-18 kg) underwent left nephrectomy with 30 min of warm ischemia, Collins C-4 flush, and 24 hr of cold storage preservation. Heterotopic autotransplantation and immediate contralateral nephrectomy was then performed in Group A-nonischemic controls (n=4), Group B-ischemic controls (n=5), and Group C-U74389G (6 mg/kg) administered preischemia and at autotransplantation (n=5). In Model 1 maximal renoprotection was demonstrated with the 6 mg/kg dose of U74389G administered after ischemia (ischemic control 72-hr serum creatinine (Cr) = 8.01+/-1.1 mg% vs. 3.32+/-0.96 mg%; ischemic control creatinine clearance = 0.069+/-0.03 ml/min vs. 0.206+/-0.04 ml/min; P<0.05). In Model 2 TBA levels were significantly lower in U74389G treated animals (88.5+/-10.0 vs. ischemic controls = 296.8+/-81.4; P=0.02). In Model 3 graft survivals were 100%, 0%, and 60% respectively. Peak Cr and BUN (mg%) were significantly greater in Group C vs. Group A, (Group A Cr = 8.59+/-0.63 vs. Group C = 12.8+/-1.01; Group A BUN = 64.1+/-2.73 vs. Group C = 104.9+/-12.21)--however, by day 10, thee were no significant differences in renal function: (Group A Cr = 2.15+/-0.3 vs. Group C = 2.10+/-0.06; Group A BUN = 27.0+/-6.0 vs. Group C = 31.1+/-6.4). These results support the beneficial effects of LPO inhibitors in models of ischemia-reperfusion, as well as preservation/transplantation, and suggest that this renoprotection correlates with decreased membrane lipid peroxidation.


Assuntos
Antioxidantes/farmacologia , Isquemia/fisiopatologia , Transplante de Rim/fisiologia , Rim/irrigação sanguínea , Preservação de Órgãos/métodos , Pregnatrienos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Nitrogênio da Ureia Sanguínea , Temperatura Baixa , Creatinina/sangue , Feminino , Sobrevivência de Enxerto , Isquemia/patologia , Isquemia/prevenção & controle , Rim/efeitos dos fármacos , Rim/patologia , Transplante de Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Necrose , Nefrectomia , Ratos , Ratos Sprague-Dawley , Suínos , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Fatores de Tempo , Transplante Autólogo , Transplante Heterotópico
19.
Biotechniques ; 20(6): 1098-103, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8780881

RESUMO

We have established rapid procedures that negatively deplete and positively select for specific murine cell populations. By using polystyrene tissue culture flasks containing a covalently bound mouse anti-rat antibody and specific anti-mouse, cell-surface antigen antibodies, we easily and efficiently depleted greater than 90% of the mature lineage cells from murine bone marrow. This selection procedure resulted in an enrichment of progenitor colonies (CFU-Cs) in murine bone marrow. Using the same polystyrene tissue culture devices, we can directly isolate CD117+ (c-kit+) murine hematopoietic cells. As few as 2000 of these CD117+ cells rescued and reconstituted lethally irradiated recipients in a murine bone marrow transplant model.


Assuntos
Separação Celular/métodos , Técnicas de Cultura/métodos , Células-Tronco Hematopoéticas , Animais , Transplante de Medula Óssea , Linhagem da Célula , Técnicas de Cultura/instrumentação , Citometria de Fluxo/métodos , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-kit/imunologia
20.
Am J Cardiol ; 61(11): 885-90, 1988 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-3354464

RESUMO

Precordial maps have been used for some 15 years to estimate the extent of myocardial injury in patients with acute anterior or lateral wall infarction. Estimates have been based on various QRS- and ST-T-derived parameters, including amplitude sum of ST elevations. Application of the electrodes, commonly 35, is cumbersome and time-consuming with the critically ill. A subset of 5 or 7 selected leads can be applied instead, and the remaining leads calculated from that subset with minimal loss of QRS and ST-T information. Maps were recorded from 100 patients within 72 hours of onset of anterior or lateral infarct. Optimal lead subsets for QRS and ST-T feature extraction were found by the sequential selection method of Lux. Subsets numbering between 2 and 15 leads were derived, with their lead-transform coefficients. Measures to estimate goodness of fit for reconstructed leads included correlations, error-to-signal ratios and root-mean-square errors. These measures were calculated separately over the QRS and ST-T complexes. Reconstructions from a 7-lead subset had a mean 0.92 correlation with ST-T in the original leads and root-mean-square error of only 0.04 mV. Sum of ST elevation differed by only 2% between original leads and reconstructions based on 5 or more leads. To confirm repeatability, lead-transform coefficients were also calculated from a training population of 50 patients and applied to the maps of the other 50.


Assuntos
Eletrocardiografia , Coração/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Eletrocardiografia/métodos , Eletrofisiologia , Humanos
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