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1.
Ochsner J ; 23(4): 296-303, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143540

RESUMO

Background: In 2009, Ochsner Health in New Orleans, Louisiana, and The University of Queensland (UQ) in Brisbane, Queensland, Australia, formed a medical school partnership. The rationale for UQ to enter this partnership was to strengthen its already strong international multicultural environment and enrich the domestic Australian student experience. The rationale for Ochsner Health was to raise its academic stature and to train high-quality physicians. This partnership is unique among US international partnerships because the intent is for graduates to practice in the United States. Methods: A new 10-year agreement began in January 2020 with further enhancements to the program. This article describes the educational philosophy informing the partnership, the programmatic design, challenges faced and overcome, and outcomes from the first 10 graduating cohorts of this medical program. Results: The UQ-Ochsner Clinical School partnership posed many challenges. UQ faced a major cultural shift to implement United States Medical Licensing Examination step preparation. Student recruitment challenges and state-specific accreditation concerns had to be solved. The coronavirus disease 2019 pandemic presented unique challenges with the strict prohibition on travel into Australia. Challenges were addressed, and the tenth graduating class completed training in December 2021. More than 850 medical students have graduated from the program, with 30% staying in Louisiana for postgraduate training. The overall first-attempt match rate of 95% exceeds the US allopathic average. Although graduates have faced stigma from their designation as international medical graduates, they have successfully matched in every specialty and in almost every US state. Conclusion: The UQ-Ochsner Clinical School partnership has been successful for the institutions involved and the students who have graduated. The overarching aim of the partnership, "train globally to serve locally," has endured. Through their training in this partnership, UQ-Ochsner Clinical School graduates bring a unique global outlook to their roles while helping to fill the increasing need for physicians in the United States.

2.
Ochsner J ; 20(3): 279-284, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33071660

RESUMO

Background: Surgical procedures require the collaboration of medical personnel with multiple skill sets who have different levels of training. Someone new to surgical procedures, such as a medical student, faces a steep learning curve. Studies have shown that video-assisted learning is associated with improved learning of surgical procedures. Methods: During their surgical rotation orientation, third-year medical students were invited via email to participate in a learning study featuring a cardiopulmonary bypass video. Study participants took a pretest, reviewed the locally developed video, and took a posttest and an attitudinal questionnaire after viewing the video. Results: A convenience sample of 31 third-year medical students participated in the study. Overall knowledge scores improved from pretest to posttest (36.9% vs 79.6%, P<0.001). In the posttest attitudinal questionnaire, students reported that they preferred video-assisted learning to reading written protocols (90.3% strongly agree/agree) and that they were more knowledgeable about the function of the cardiopulmonary bypass machine (80.7% strongly agree/agree) after viewing the video. Students also reported that the video would be useful during their surgical clerkships (90.4% strongly agree/agree). Conclusion: Video-assisted learning was associated with comprehension of the material immediately after viewing the video, and medical students considered it to be appropriate and useful. This educational video may benefit other learners who are entering the cardiopulmonary bypass operating room for the first time.

3.
Science ; 264(5164): 1434-7, 1994 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-17838426

RESUMO

A corrected radiocarbon age of 11,050 +/- 14 years before present for an advance of the Franz Josef Glacier to the Waiho Loop terminal moraine on the western flank of New Zealand's Southern Alps shows that glacier advance on a South Pacific island was synchronous with initiation of the Younger Dryas in the North Atlantic region. Hence, cooling at the beginning of the Younger Dryas probably reflects global rather than regional forcing. The source for Younger Dryas climatic cooling may thus lie in the atmosphere rather than in a North Atlantic thermohaline switch.

4.
Science ; 159(3811): 187-9, 1968 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-17792355

RESUMO

Potassium-argon dates for three samples of basaltic scoria from Taylor Valley, on the west side of McMurdo Sound, indicate that the basalt, which antedates and postdates major glaciations, is at least 2.7 million years old.

5.
Science ; 260(5108): 667-70, 1993 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-17812227

RESUMO

The preservation, age, and stratigraphic relation of an in situ ashfall layer with an underlying desert pavement in Arena Valley, southern Victoria Land, indicate that a cold-desert climate has persisted in Arena Valley during the past 4.3 million years. These data indicate that the present East Antarctic Ice Sheet has endured for this time and that average temperatures during the Pliocene in Arena Valley were no greater than 3 degrees C above present values. One implication is that the collapse of the East Antarctic Ice Sheet due to greenhouse warming is unlikely, even if global atmospheric temperatures rise to levels last experienced during mid-Pliocene times.

6.
Science ; 269(5230): 1541-9, 1995 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-17789444

RESUMO

A radiocarbon chronology shows that piedmont glacier lobes in the Chilean Andes achieved maxima during the last glaciation at 13,900 to 14,890, 21,000, 23,060, 26,940, 29,600, and >/=33,500 carbon-14 years before present ((14)C yr B.P.) in a cold and wet Subantarctic Parkland environment. The last glaciation ended with massive collapse of ice lobes close to 14,000(14)C yr B.P., accompanied by an influx of North Patagonian Rain Forest species. In the Southern Alps of New Zealand, additional glacial maxima are registered at 17,720(14)C yr B.P., and at the beginning of the Younger Dryas at 11,050 (14)C yr B. P. These glacial maxima in mid-latitude mountains rimming the South Pacific were coeval with ice-rafting pulses in the North Atlantic Ocean. Furthermore, the last termination began suddenly and simultaneously in both polar hemispheres before the resumption of the modern mode of deep-water production in the Nordic Seas. Such interhemispheric coupling implies a global atmospheric signal rather than regional climatic changes caused by North Atlantic thermohaline switches or Laurentide ice surges.

7.
Ochsner J ; 19(3): 188-193, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31528127

RESUMO

Background: Pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (Truvada) is highly effective at preventing human immunodeficiency virus (HIV) transmission in high-risk populations, including in men who have sex with men (MSM). In 2019, the US Preventive Services Task Force released an A recommendation to offer PrEP to persons at high risk of HIV acquisition. Despite the demonstrated efficacy of PrEP, areas with high HIV incidence, such as Louisiana, have historically had low PrEP prescription rates. The objective of this study was to determine the factors associated with whether providers in the Ochsner Health System (OHS) discussed PrEP with HIV-negative MSM patients. Methods: Investigators extracted electronic medical record data on all HIV-negative MSM patients who had at least one outpatient visit at OHS between July 1, 2012 and July 1, 2016 and manually reviewed a random sample of 115 charts. Results: Subjects were predominantly Caucasian (75.7%) with a mean age of 37.6 years. A PrEP discussion was documented for 34 (29.6%) patients. Multivariate modeling showed that having a PrEP discussion was associated with 3 factors: being assigned to a primary care provider known to specialize in MSM care (odds ratio [OR] 5.05, 95% confidence interval [CI] 1.81-14.10; P=0.002), having a documented history (positive or negative) of sexually transmitted infection vs no documentation (OR 5.41, 95% CI 1.80-16.23; P=0.003), and having documentation of condom use (consistent or inconsistent) vs no documentation (OR 3.32, 95% CI 1.27-8.74; P=0.015). Conclusion: Despite evidence that PrEP significantly reduces sexual transmission of HIV in MSM, PrEP discussions with MSM across OHS were undesirably low. Additional resources need to be aimed at increasing PrEP uptake and should focus on providing skills-based training and education in PrEP and MSM care to healthcare providers. With increased knowledge of and familiarity with PrEP prescribing guidelines, more providers will be better equipped to identify at-risk patients and to discuss prevention options such as PrEP.

8.
Plant Dis ; 92(9): 1273-1279, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30769451

RESUMO

Cylindrocladium buxicola is a fungal pathogen that causes a severe leaf and twig blight on Buxus spp. Laboratory experiments were carried out to study the in vitro effect of 13 fungicides on mycelial growth and conidia germination of the fungus. Based on the values of the effective concentration at which mycelial growth was inhibited by 50%, the fungicide Stroby (kresoxim-methyl) and the combined fungicides Opponent (epoxiconazole + kresoxim-methyl + pyraclostrobin), Opera (epoxiconazole + pyraclostrobin), and Signum (boscalid + pyraclostrobin) were the most effective at inhibiting mycelial growth and conidia germination. Pathogenicity assays showed that the host range of the fungus was not limited to the genus Buxus because Sarcococca sp. also was susceptible. None of the 10 boxwood species and cultivars tested were immune to the disease, although Buxus balearica as well as Sarcococca sp. showed significantly lower levels of infection as measured by the expression of leaf symptoms and the number of conidia produced on host tissue, the latter probably contributing to the apparent resistance of these species in the field. Microscopic observation showed that disease development was very rapid and aggressive on B. sempervirens 'Suffruticosa' where it was able to survive at least 5 years on decomposing fallen leaves.

9.
Cancer Res ; 51(19): 5425-9, 1991 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-1913661

RESUMO

The immunogenicity of human anti-idiotypic antibody has been investigated using a human monoclonal anti-idiotypic antibody (105AD7) which interacts with the binding site of 791T/36, a mouse monoclonal antibody against gp72 antigen. This antigen is frequently expressed in gastrointestinal cancer, therefore, six patients with advanced colorectal cancer have been immunized with 105AD7 as an aluminum hydroxide gel precipitate in a phase I clinical study. Cryopreserved blood mononuclear cells were tested for in vitro proliferative responses by [3H]thymidine incorporation; plasma samples were tested by enzyme-linked immunosorbent assay for anti-anti-idiotypic and antitumor antibodies, and for interleukin 2. Proliferative responses to gp72 positive tumor cells were seen in four of five patients tested; parallel in vitro responses to 105AD7 anti-idiotypic antibody were seen in most of these patients. Interleukin 2 was detected in the plasma of four of six patients after 105AD7 immunization, with peak levels up to 7 units/ml. No toxicity related to anti-idiotype immunization and no antitumor or anti-anti-idiotype antibodies were seen. This study shows that human monoclonal anti-idiotype 105AD7 is immunogenic in cancer patients, inducing cellular antitumor responses and interleukin 2 production. This suggests that human monoclonal anti-idiotype antibodies may have considerable potential for immunotherapy of human cancer.


Assuntos
Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Neoplasias Colorretais/terapia , Imunoterapia Ativa , Interleucina-2/sangue , Adulto , Idoso , Análise de Variância , Anticorpos Anti-Idiotípicos/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Divisão Celular/efeitos dos fármacos , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
10.
Cancer Res ; 54(18): 4837-40, 1994 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-8069847

RESUMO

A human antiidiotypic monoclonal antibody (105AD7) has been shown to induce antitumor cellular responses in animals and appears to prolong survival in patients with metastatic colorectal cancer without associated toxicity. Proliferative leukocyte responses to the targeted tumor antigen gp72 were observed in these patients and plasma interleukin 2 levels were increased following immunization. Autologous tumor tissue was not available in these patients, so antitumor cytotoxicity could not be measured. This issue has now been addressed in an adjuvant clinical study in primary rectal cancer patients. Six patients with rectal cancer were immunized preoperatively with 105AD7. Peripheral blood lymphocytes taken prior to immunization were tested against tumor cells extracted from biopsies also obtained prior to immunization or from natural killer (NK)-sensitive target cells. Cryopreserved lymphocytes taken before and after tumor immunization, fresh peripheral blood lymphocytes taken immediately prior to surgery, and lymphocytes from tumor-draining lymph nodes were tested against autologous cells from the resected specimen or NK-sensitive target cells. Significant killing of autologous tumor cells, which was not due to NK activity, was seen with cryopreserved lymphocytes or lymph node cells of three patients at 1-2 weeks postimmunization with 105AD7 but not on pretreatment biopsies. Enhanced NK activity was seen 2-3 weeks postimmunization in 3 of 6 patients. These results indicate that 105AD7 human monoclonal antibody immunization enhances cytotoxicity in rectal cancer patients by specific and nonspecific effector mechanisms.


Assuntos
Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Imunização/métodos , Neoplasias Retais/terapia , Idoso , Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Monoclonais/imunologia , Feminino , Humanos , Imunidade Celular , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/imunologia , Neoplasias Retais/patologia , Linfócitos T Citotóxicos/imunologia , Fatores de Tempo
11.
Ochsner J ; 16(1): 27-31, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27046400

RESUMO

BACKGROUND: Ochsner Clinical School (OCS) is a unique partnership between Ochsner Health System in New Orleans, LA, and The University of Queensland (UQ) School of Medicine in Brisbane, Australia. OCS trains physicians in global medicine and promotes careers in primary care through its unique structure. The purpose of this study was to determine how OCS graduates perform in the National Resident Matching Program (NRMP)-The Match-compared to applicants from other types of medical schools. METHODS: The match outcomes for all OCS graduates since the first graduating class in November 2012 were compared to the match outcomes in the NRMP database for graduates from other types of medical schools in the years 2013-2015. We also examined the number of OCS students electing residencies in primary care compared to the number of US medical school graduates overall during the same time period of 2013-2015. RESULTS: The cumulative match rate from 2013-2015 for applicants from OCS was 91.8%. The OCS graduates' match rate was greater than the match rate for US citizen graduates of international medical schools during the same period (53.0% vs 91.8% [z=6.066, P<0.0002]), greater than the match rate for applicants from US osteopathic medical schools (77.3% vs 91.8% [z=25.233, P<0.0002]), and greater than the match rate for applicants from Canadian medical schools (62.7% vs 91.8% [z=3.815, P<0.0002]). The OCS match rate was not significantly different from that of US medical school graduates: 94.0% vs 91.8% (z=-0.728, P=0.4666). During the 2013-2015 time frame, 44.3% of OCS graduates chose residencies in primary care fields compared to 38.3% of US graduates (z=-0.9634, P=0.337). CONCLUSION: Graduates of OCS are obtaining residency positions through The Match at rates comparable to those of US medical school graduates and at rates significantly greater than other groups, and we are seeing a trend in the number of graduates choosing careers in primary care.

12.
J Clin Oncol ; 18(2): 363-70, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10637251

RESUMO

PURPOSE: More effective intravesical agents are required to limit the recurrence and progression of superficial bladder cancer. This study assessed the ability of copper-67 ((67)Cu)-C595 murine antimucin monoclonal antibody to bind selectively to superficial bladder tumors when administered intravesically, with a view to its development for therapy. PATIENTS AND METHODS: Approximately 20 MBq of (67)Cu-C595 monoclonal antibody was administered intravesically to 16 patients with a clinical indication of superficial bladder cancer. After 1 hour, the bladder was drained and irrigated. Tissue uptake was assessed by imaging and by the assay of tumor and normal tissues obtained by endoscopic resection. RESULTS: Tumor was correctly identified in the images of 12 of 15 patients who were subsequently found to have tumors. Assay of biopsy samples at 2 hours showed a mean tumor uptake of 59.4% of the injected dose per kilogram (SD = 48.0), with a tumor-to-normal tissue ratio of 14.6:1 (SD = 20). After 24 hours (n = 5), this decreased to 4.3% of the injected dose per kilogram (SD = 2.9), with a tumor-to-normal tissue ratio of 1.8:1 (SD = 0.8). CONCLUSION: This study indicates a promising method for the treatment of superficial bladder cancer. Although the mean initial tumor uptake was high, effective therapy of bladder tumors will require an increased retention of the cytotoxic radionuclide in tumor tissue.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Radioisótopos de Cobre/uso terapêutico , Radioimunoterapia , Neoplasias da Bexiga Urinária/radioterapia , Administração Intravesical , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/farmacocinética , Sítios de Ligação de Anticorpos , Radioisótopos de Cobre/farmacocinética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mucina-1/imunologia , Mucina-1/metabolismo , Mucinas/imunologia , Cintilografia , Neoplasias da Bexiga Urinária/diagnóstico por imagem
13.
Acad Med ; 90(11): 1532-5, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26061860

RESUMO

PROBLEM: Medical schools face barriers to recruiting physicians to teach in the ambulatory setting for many reasons, including time required to teach, loss of productivity when learners are present, and physicians' uncertainty about how to teach. APPROACH: In 2012, the primary care department of the University of Queensland-Ochsner Clinical School (UQ-OCS) implemented an innovative model for recruiting primary care physicians to teach students in their clinics. The model's three-pronged approach allows protected teaching time, allocates tuition money to reimburse physicians for teaching via educational value unit (EVU) tracking, and includes a faculty development program. OUTCOMES: In the first two years of EVU tracking (academic years 2012 and 2013), 5,530 EVUs were provided by 48 primary care faculty teaching 60 students at 11 sites. In academic year 2013, the first year in which tuition dollars were available to fund teaching by primary care faculty, over $120,000 in tuition money was transferred to the department to pay for EVUs. No faculty in 2012 or 2013 experienced a change in salary as a result of teaching activities. Faculty development workshops have been well attended. The general practice clerkship has been the top-rated third-year clerkship by students for the first three years of clinical rotations at the UQ-OCS. NEXT STEPS: A qualitative study to describe the barriers to and solutions for recruiting physicians to teach students in ambulatory settings is planned. Other studies will evaluate the effectiveness of faculty development efforts and the impact of students' presence on patients' access to clinic appointments.


Assuntos
Assistência Ambulatorial , Educação de Graduação em Medicina , Medicina de Família e Comunidade/educação , Seleção de Pessoal , Médicos de Atenção Primária , Mobilidade Ocupacional , Competência Clínica , Humanos , Louisiana , Modelos Organizacionais , Queensland , Salários e Benefícios , Fatores de Tempo , Recursos Humanos
14.
Ochsner J ; 15(1): 13-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25829875

RESUMO

BACKGROUND: Diabetic patients should receive self-management education to improve self-care and quality of life but are frequently unable to attend such programs because of the time commitment. We instituted an intensive 2-hour Diabetes Boot Camp to provide this education in a condensed time frame. The objective was to determine the long-term effect of the boot camp on mean hemoglobin A1c (HgA1c) levels in patients with diabetes compared to diabetic patients receiving the standard of care. METHODS: The Diabetes Boot Camp population was defined as all diabetic patients referred to the boot camp from the 10 highest utilizing physicians between August 2009 and August 2010. A control population was randomly selected from these same physicians' diabetic patients during the same period. Baseline and postintervention HgA1c measurements on the same patients in both groups were extracted from the electronic medical record. Subpopulations studied included those with HgA1c ≥9% and <9% at baseline. To evaluate long-term effects, we compared HgA1c levels 3 years later (between July 1, 2012 and December 31, 2012) for all groups. RESULTS: Using comparison-over-time analysis, the overall boot camp group (n=69) showed a mean decrease in HgA1c from 8.57% (SD ± 2.32%) to 7.76% (SD ± 1.85%) vs an increase from 7.92% (SD ± 1.58%) to 8.22% (SD ± 1.82%) in the control group (n=107, P<0.001). Mean length of follow-up was 3.2 (SD ± 0.54) years. CONCLUSION: An intensive 2-hour multidisciplinary diabetes clinic was associated with significant long-term improvements in glycemic control in diabetic participants of the clinic.

15.
Eur J Cancer ; 31A(2): 214-21, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7718328

RESUMO

Polymerase chain reaction (PCR) products representative of the DNA sequence coding for the variable heavy (VH) and the variable light (VL) chains of an antiMUC1 mucin monoclonal antibody, C595, have been produced. These products were cloned, sequenced, and the primary amino acid sequences of the VH and VL regions deduced. The hypervariable complementarity determining regions (CDRs) and framework regions in the heavy and light chains were located, and homologies with canonical forms for the CDR loops L1, L2, L3, H1 and H2 were identified by database searching. The structure for the H3 loop was calculated directly. Computational molecular modelling was accomplished using the fully automated AbM package (Oxford Molecular, Oxford, U.K.). Energy minimisation was performed using the program InsightII (Biosym, San Diego, California, U.S.A.). The investigation provides a basis for the molecular analysis of the antigen binding site of the C595 antibody with the aim to identify key residues and interactions involved in the immune recognition of the C595 antibody defined epitope, which is expressed in the majority of breast and ovarian carcinomas.


Assuntos
Anticorpos Monoclonais/química , Região Variável de Imunoglobulina/química , Mucinas/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/genética , Sequência de Bases , Sítios de Ligação de Anticorpos , DNA/química , Camundongos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase
16.
J Nucl Med ; 42(5): 726-32, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11337567

RESUMO

UNLABELLED: Bladder cancer was responsible for >12,000 deaths in the United States in 1999. The high-molecular-weight glycoprotein MUC1 mucin is overexpressed on bladder tumors and represents a useful target for radioimmunoscintigraphy and radioimmunotherapy. We report on the production and initial tracer studies of a 188Re-antibody complex directed against this target and intended for intravesical radioimmunotherapy of superficial bladder cancer. METHODS: 188Re perrhenate was eluted from a 188W/188Re generator. C595 antibody was reduced with 2-mercaptoethanol and was labeled in the presence of stannous tartrate. The final reaction mixture contained high-molecular-weight contamination, which was removed from the complex using an affinity separation technique. The specificity and integrity of the antibody complex were tested by radioimmunoassay and size exclusion chromatography. Tumor localization was investigated using an ex vivo model in human cystectomy specimens. Tracer amounts of the complex were also administered intravesically to three patients with bladder cancer, who were then imaged by gamma scintigraphy. RESULTS: The complex was immunoreactive (70% +/- 17%) and specific for MUC1 antigens. A peak corresponding to a protein of 150 kDa was observed on size exclusion chromatography, showing that the complex was homogeneous. Binding to bladder tumors was observed in an ex vivo model in which tumors were successfully imaged in four specimens. The mean tumor-to-normal tissue ratio in ex vivo bladders was 7:1. Tumor uptake after intravesical administration was confirmed in three patients with bladder cancer (mean tumor-to-normal tissue ratio, 4:1). CONCLUSION: The C595 antibody was labeled with 188Re, providing a radioimmunoconjugate with high immunoreactivity and specificity. Its ability to localize in tumors both in an ex vivo model and after intravesical administration to patients has been shown. This approach will now be extended for the therapy of superficial bladder cancer.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Carcinoma de Células de Transição/radioterapia , Radioimunoterapia , Radioisótopos/uso terapêutico , Rênio/uso terapêutico , Neoplasias da Bexiga Urinária/radioterapia , Anticorpos Monoclonais/química , Especificidade de Anticorpos , Cromatografia em Gel , Estabilidade de Medicamentos , Humanos , Técnicas In Vitro , Marcação por Isótopo , Mucina-1/análise , Radioisótopos/química , Cintilografia , Rênio/química , Bexiga Urinária/diagnóstico por imagem
17.
Cancer Lett ; 70(3): 143-50, 1993 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-7689035

RESUMO

A strategy for directing and enhancing B cell immune responses against synthetic peptide determinants has been developed in order to produce antibodies specifically against protein epitopes of clinical relevance. A peptide sequence based upon the MUC-1 mucin protein core was selected for this purpose since anti-MUC-1 antibodies have proven diagnostic application and therapeutic potential in human breast and ovarian cancer. Peptide constructs were synthesised co-linearly linking the immunodominant B cell determinant region, PDTRPAP, in the protein core of the MUC-1 mucin, to sequence 111-120 of influenza haemagglutinin A/X-31, a determinant recognised by T helper cells through association with MHC class II molecules. Induction of anti-MUC-1 antibodies to the B cell determinant region by immunisation with peptide was shown to be dependent upon both the presence and the position of the T cell determinant. In addition, haplotype mismatching with respect to the T cell determinant resulted in a significant lowering of the anti-MUC-1 antibody response in peptide construct immunised mice. These findings are relevant to the design of immunogens to produce antibodies against peptide epitopes of tumour associated proteins and glycoproteins.


Assuntos
Anticorpos Antineoplásicos/biossíntese , Antígenos de Neoplasias/imunologia , Neoplasias da Mama/imunologia , Glicoproteínas de Membrana/imunologia , Mucinas/imunologia , Proteínas de Neoplasias/imunologia , Fragmentos de Peptídeos/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Antineoplásicos/imunologia , Antígenos de Neoplasias/química , Linfócitos B/imunologia , Ensaio de Imunoadsorção Enzimática , Epitopos/química , Epitopos/imunologia , Feminino , Haplótipos , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Hemaglutininas Virais/imunologia , Soros Imunes/imunologia , Imunização , Imunoterapia , Glicoproteínas de Membrana/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Dados de Sequência Molecular , Mucina-1 , Mucinas/química , Proteínas de Neoplasias/química , Mapeamento de Peptídeos , Linfócitos T/imunologia , Proteínas do Envelope Viral/imunologia
18.
Science ; 271(5249): 669-70, 1996 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-17814907
19.
Fertil Steril ; 76(1): 67-74, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11438321

RESUMO

OBJECTIVE: To compare the efficacy and safety of 250 microg and 500 microg of recombinant hCG with 10,000 U USP of urinary hCG in assisted reproduction technology. DESIGN: Open, comparative, randomized, prospective clinical study. SETTING: Twenty tertiary care U.S. infertility centers. PATIENT(S): Two hundred ninety-seven ovulatory infertile women undergoing a single cycle of assisted reproduction technology. INTERVENTION(S): Patients were randomized 1:1:1 to 250 microg of recombinant hCG SC, 500 microg of recombinant hCG SC, or 10,000 U USP urinary hCG IM after completing gonadotropin stimulation. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved per patient receiving hCG. Also, measures of oocyte maturity, embryo development, and luteal function, as well as pregnancy and pregnancy outcome. Adverse safety events, laboratory changes, local tolerance, and immunogenicity were also assessed. RESULT(S): Mean numbers of oocytes retrieved per treatment group were equivalent, 13.6, 14.6, and 13.7 with 250 microg of recombinant hCG, 500 microg of recombinant hCG, and urinary hCG, respectively. The numbers of 2PN fertilized oocytes on day 1 after oocyte retrieval, and 2PN or cleaved embryos on the day of embryo transfer, were significantly higher with 500 microg of recombinant hCG than with the lower dose. However, the incidence of adverse events also tended to be higher with this dose. CONCLUSION(S): Recombinant hCG is effective and well tolerated in the induction of final follicular maturation and luteinization in women undergoing assisted reproduction technology. Recombinant hCG (250 microg) SC is equivalent to 10,000 U USP of urinary hCG in this indication.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/uso terapêutico , Transferência Embrionária , Fertilização in vitro , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/fisiologia , Técnicas Reprodutivas , Adulto , Gonadotropina Coriônica/efeitos adversos , Fase de Clivagem do Zigoto , Relação Dose-Resposta a Droga , Feminino , Fertilização , Humanos , Infertilidade Feminina/terapia , Oócitos/fisiologia , Estudos Prospectivos , Proteínas Recombinantes , Coleta de Tecidos e Órgãos , Resultado do Tratamento
20.
J Hosp Infect ; 8(1): 39-46, 1986 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2875100

RESUMO

Suspensions of Escherichia coli and Klebsiella aerogenes were exposed to low levels of chlorhexidine, which had little effect on their in vitro viability. A substantial reduction in their in vivo infectivity measured by intraperitoneal inoculation of mice was found. This selective reduction in bacterial infectivity by chlorhexidine should be taken into account when conventional in vitro tests are used to assess the clinical effectiveness of chlorhexidine-containing antiseptics.


Assuntos
Clorexidina/farmacologia , Escherichia coli/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Animais , Escherichia coli/patogenicidade , Klebsiella pneumoniae/patogenicidade , Camundongos , Virulência/efeitos dos fármacos
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