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1.
Zhonghua Yan Ke Za Zhi ; 60(1): 49-55, 2024 Jan 11.
Artigo em Zh | MEDLINE | ID: mdl-38199768

RESUMO

Objective: To observe the efficacy and safety of botulinum toxin A (BTA) injection in the treatment of acute comitant esotropia (ACE) with different doses. Methods: This retrospective cohort study included data from patients with ACE who received BTA injection treatment at the First Affiliated Hospital of Zhengzhou University from June 2019 to June 2022. All patients underwent routine ophthalmic examinations, including best-corrected visual acuity (BCVA), spherical equivalent (SE), as well as specialized examinations for strabismus, including the degree of esotropia, eye movement status, and binocular visual function. Patients were categorized into small esotropia [≤60 prism diopters (PD)] and large esotropia (>60 PD) groups based on the pre-treatment degree of esotropia. Each group was further divided into 2.5 U and 5.0 U dose subgroups. Monocular injections were administered to the non-dominant eye. The esotropia degree was recorded and compared at 1, 2, 3, and 6 months of follow-up. The proportion of effectively treated patients in each group was documented. The number of cases with various levels of visual functions (including simultaneous vision, near stereopsis, and distance stereopsis) at 6 months post-treatment was compared, and complications during the follow-up period were observed. Statistical analyses were conducted using t-tests, Mann-Whitney U tests, and χ2 tests. Results: A total of 70 patients were included in the study, comprising 46 males and 24 females, with a median age of 5.0 (4.0, 8.3) years. Among them, 37 patients had small esotropia, with 25 in the 2.5 U group and 12 in the 5.0 U group. Thirty-three patients had large esotropia, with 18 in the 2.5 U group and 15 in the 5.0 U group. There were no statistically significant differences in baseline data, including age, duration of the condition, pre-treatment esotropia degree, BCVA and SE, between the two dose groups in both small and large esotropia patients (all P>0.05). In small esotropia patients, at 1 and 2 months post-treatment, the esotropia degree in the 5.0 U group was -20.00 (-37.50, -7.00) and 0.00 (0.00, 0.00) PD, respectively, which was significantly lower than the 0.00 (-10.00, 4.50) and 5.00 (0.00, 6.50) PD in the 2.5 U group (all P<0.05). At 3 and 6 months post-treatment, the esotropia degree in the 2.5 U group was 5.00 (0.00, 15.00) and 2.00 (0.00, 6.00) PD, respectively, while in the 5.0 U group, it was 0.00 (0.00, 4.50) and 0.00 (0.00, 3.75) PD, with no statistically significant differences between the two groups (all P>0.05). In the 2.5 U group, 20 cases were effectively treated, accounting for 80.0%, while in the 5.0 U group, 10 cases were effective, accounting for 10/12, with no significant difference between the two groups (P>0.05). In the 2.5 U group and the 5.0 U group, the proportions of cases with various levels of visual functions were as follows: simultaneous vision, 76.0% (19/25) and 10/12; near stereopsis, 48.0% (12/25) and 7/12; distance stereopsis, 44.0% (11/25) and 7/12, respectively. No statistically significant differences were observed in these proportions (all P>0.05). In patients with large esotropia, the esotropia degrees in the 5.0 U group at various follow-up times were -5.00 (-25.00, 5.00), 0.00 (0.00, 7.00), 2.00 (0.00, 10.00), and 5.00 (0.00, 7.00) PD, respectively. For the 2.5 U group, the corresponding values were 5.00 (2.75, 27.75), 10.00 (3.75, 24.75), 12.00 (3.75, 38.75), and 14.00 (3.50, 54.00) PD, respectively. The esotropia degrees in the 5.0 U group were consistently lower than those in the 2.5 U group (all P<0.05). The proportion of effective treatment in the 5.0 U group (13/15) was higher than that in the 2.5 U group (9/18), and the proportion of cases with distance stereopsis in the 5.0 U group (9/15) was higher than that in the 2.5 U group (4/18), both showing statistically significant differences (all P<0.05). The number of cases with simultaneous vision and near stereopsis showed no significant differences between the two groups (all P>0.05). The proportion of complications in the 2.5 U and 5.0 U groups in both large and small esotropia patients was 9/18, 13/15, 80.0% (20/25), and 10/12, respectively, with no statistically significant differences (all P>0.05). All complications spontaneously resolved within 3 months post-treatment. Conclusions: BTA injection is effective in the treatment of ACE, and for ACE patients with esotropia degrees greater than 60 PD, increasing the injection dose to 5.0 U can achieve better therapeutic outcomes.


Assuntos
Toxinas Botulínicas Tipo A , Esotropia , Estrabismo , Feminino , Masculino , Humanos , Toxinas Botulínicas Tipo A/uso terapêutico , Esotropia/tratamento farmacológico , Estudos Retrospectivos , Doença Aguda
2.
Opt Express ; 29(22): 36321-36327, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34809045

RESUMO

We present a high power optical parametric oscillator (OPO) synchronously pumped by the second-harmonic of a modelocked 1030-nm thin-disk laser (TDL) oscillator. The OPO delivers an average power of 51.1 W around degeneracy (1030 nm) with a 10.2-MHz repetition-rate. After extra-cavity dispersion compensation using dispersive mirrors, we obtain a pulse duration of 169 fs, which is 4.6× shorter than the TDL pulse duration of 770 fs. The TDL has 250 W average power, which is converted to 215 W at the second-harmonic. Hence, the OPO exhibits a high photon conversion efficiency of 47% (ratio of signal photons to 515-nm pump photons). Moreover, the OPO generates a peak power of 26.2 MW, which is very similar to the 28.0-MW peak power of the TDL. To facilitate continuous tuning around degeneracy and convenient extraction of the pump and idler beams, the OPO is operated in a noncollinear configuration. A linear cavity configuration was chosen since it offers easy alignment and straightforward cavity length tuning. To the best of our knowledge, this source has the highest average power generated by any ultrafast OPO, and the shortest pulse duration for any >5-W OPO. This result is an important step to adding wavelength tunability to high power Yb-based laser sources without the complexity of either laser or parametric amplifier systems.

3.
Opt Express ; 29(12): 18059-18069, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34154073

RESUMO

Silicate bonding is a flexible bonding method that enables room-temperature bonding of many types of materials with only moderate flatness constraints. It is a promising approach for bonding components in high power laser systems, since it results in a thin and low-absorption interface layer between the bonded materials. Here we demonstrate for the first time silicate bonding of a sapphire window to a SEmiconductor Saturable Absorber Mirror (SESAM) and use the composite structure to mode-lock a high-power thin-disk laser. We characterize the fabricated devices both theoretically and experimentally and show how the thermally induced lens of the composite structure can be tuned both in magnitude and sign via the thickness of the sapphire window. We demonstrate mode-locking of a high-power thin-disk laser oscillator with these devices. The altered thermal lens allows us to increase the output power to 233 W, a 70-W-improvement compared to the results achieved with a state-of-the-art SESAM in the same cavity.

4.
Opt Express ; 27(22): 31465-31474, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31684382

RESUMO

We report a semiconductor saturable absorber mirror (SESAM)-modelocked thin-disk laser oscillator delivering a record 350-W average output power with 940-fs, 39-µJ pulses at 8.88-MHz repetition rate and 37-MW peak power. This oscillator is based on the Yb:YAG gain material and has a large pump spot on the disk. The cavity design includes an imaging scheme, which results in multiple reflections on the disk gain medium to enable a larger output coupling rate compared to those used in thin-disk oscillators with a single reflection on the disk. This reduces the intracavity power for a given output power, thus decreasing the stress on the intracavity components. We operate the laser in a low-pressure environment in order to limit the disk's thermal lensing and drastically reduce the nonlinearity picked up in the intracavity air medium. The combination of the imaging scheme and low-pressure operation paves the way to further power scaling of ultrafast thin-disk oscillators toward the kW milestone.

5.
Br Med Bull ; 124(1): 135-155, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29140418

RESUMO

INTRODUCTION: The escalation in the prevalence of obesity throughout the world has led to an upsurge in the number of obese surgical patients to whom perioperative care needs to be delivered. SOURCES OF DATA: After determining the scope of the review, the authors used PubMed with select phrases encompassing the words in the scope. Both preclinical and clinical reports were considered. AREAS OF AGREEMENT: There were no controversies regarding preoperative management and the intraoperative care of the obese surgical patient. AREAS OF CONTROVERSY: Is there a healthy obese state that gives rise to the obesity paradox regarding postoperative complications? GROWING POINTS: This review considers how to prepare for and manage the obese surgical patient through the entire spectrum, from preoperative assessment to possible postoperative intensive care. AREAS TIMELY FOR DEVELOPING RESEARCH: What results in an obese patient developing 'unhealthy' obesity?


Assuntos
Analgesia/métodos , Anestesia/métodos , Obesidade/cirurgia , Assistência Perioperatória , Complicações Pós-Operatórias/prevenção & controle , Protocolos Clínicos , Comorbidade , Relação Dose-Resposta a Droga , Humanos , Obesidade/complicações , Assistência Perioperatória/métodos , Guias de Prática Clínica como Assunto , Fatores de Risco
6.
Refuat Hapeh Vehashinayim (1993) ; 33(1): 6-14, 59, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27295927

RESUMO

OBJECTIVE: No controlled clinical study has evaluated Oral Health Related Quality of Life (OHRQOL) of immediately placed and loaded implants retaining mandibular overdentures. This pilot study evaluated the impact of immediate loading of delayed versus immediately placed dental implants on overdenture patients' OHRQOL. MATERIALS AND METHODS: Two patient treatment groups received a maxillary conventional complete denture, opposing a mandibular overdenture immediately loaded on implants with ball attachments; In group one a delayed implant placement surgical protocol was followed, whereas in group two, patients had mandibular teeth extracted and two implants immediately placed. OHRQOL for these patients was evaluated using a visual analog scale for 48 questions related to 6 domains; comfort, function, speech, esthetics, self-image and dental health. RESULTS: There was no significant difference between the two groups when comparing answers to the pre- and post-treatment questionnaires. Pooled data showed significant differences for all domains between the pre-treatment and post-treatment responses, denoting improvement after an implant retained mandibular overdenture was delivered. CONCLUSION: There was an improved quality of life in patients receiving immediately loaded mandibular overdentures supported by either delayed or immediately placed implants.


Assuntos
Implantes Dentários , Prótese Dentária Fixada por Implante , Revestimento de Dentadura , Qualidade de Vida , Idoso , Planejamento de Dentadura , Feminino , Humanos , Masculino , Mandíbula , Pessoa de Meia-Idade , Projetos Piloto , Inquéritos e Questionários , Fatores de Tempo
7.
Artigo em Zh | MEDLINE | ID: mdl-27514262

RESUMO

OBJECTIVE: To investigate the characteristics of 136 patients with occupational diseases, to summarize key techniques used in field investigation, and to provide a scientific basis for the development of standard operating procedures for field investigation of occupational disease diagnosis. METHODS: Field investigation and routine data analysis were performed to analyze the cases diagnosed by Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from January 2009 to December 2014. RESULTS: A total of 136 cases of occupational diseases were diagnosed by Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from 2009 to 2014, and there were 66 cases of leukemia, 18 cases of suspected occupational benzene poisoning, 12 cases of suspected occupational handarm vibration disease, and 11 cases of suspected pneumoconiosis. Of all these patients, 41.91% were engaged in at least three types of work, 70.59% were exposed to at least three types of chemicals, 25.74% experienced changes in technical processes and chemicals, and 47.06% had disputes on the chemicals they were exposed to during verification by both parties. Occupational hazard factors were detected. Most samples (358)were used to measure benzene concentration in workplace air, among which 11.7% had a benzene concentration of >6.00 mg/m(3)(exceeding standard), 13.41% had a benzene concentration of 3.26~6.00 mg/m(3), 75.42% had a benzene concentration of<0.03 to <3.25 mg/m(3). The samples of suspected occupational hand-arm vibration disease, suspected pneumoconiosis, and suspected occupational noiseinduced hearing loss had high overstandard rates (100%, 93.8%, and 83.3%, respectively). CONCLUSION: Field investigation of occupational disease diagnosis reveals large numbers of cases of leukemia, suspected occupational benzene poisoning, suspected occupational hand-arm vibration disease, and suspected pneumoconiosis. The key aspects of field investigation include confirmation of the history of occupational exposure, identification of occupational hazard factors, confirmation of the changes in technical processes and chemicals, detection of occupational hazard factors, sampling and analysis of raw materials, and epidemiological investigation of workers with the same type of work.


Assuntos
Doenças Profissionais , Benzeno , Síndrome da Vibração do Segmento Mão-Braço , Humanos , Exposição Ocupacional , Pneumoconiose , Vibração
9.
Eur J Dent Educ ; 19(1): 8-15, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25756104

RESUMO

OBJECTIVE: Peer assessment is grounded in philosophies of active learning, and it would seem that this tool is a viable method for critical thinking development. The purpose of this article was to present how junior students at Case Western Reserve University School of Dental Medicine (CWRU) perceive the value of a peer-assessment activity in the context of a treatment planning course. METHODOLOGY: As a part of the final exam for the junior year Treatment Planning course, students were requested to evaluate a de-identified assignment submitted by one of their peers. Following the exam, a survey was sent to the students to determine how they perceived the peer-assessment activity and how this relates to other learning experiences in the course. RESULTS: Our results show that students' perception of the benefit of peer grading was not associated with any individual peer-assignment characteristics, or course characteristics. Similar results were obtained regarding the perceived benefit of identifying evidence. Moderate correlations were observed between peer evaluation characteristics. CONCLUSIONS: It was concluded that: (i) junior dental students are not homogenous in their opinions regarding the value of an activity related to evaluation of a peer's assignment and (ii) student's perceptions regarding the peer-grading component of peer assessment were not correlated with perceptions related to other learning processes in the treatment planning course.


Assuntos
Educação em Odontologia/métodos , Avaliação Educacional/métodos , Planejamento de Assistência ao Paciente , Revisão por Pares , Estudantes de Odontologia/psicologia , Adulto , Feminino , Humanos , Masculino , Percepção , Inquéritos e Questionários
10.
Antimicrob Resist Infect Control ; 12(1): 53, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37254208

RESUMO

BACKGROUND: The Asia Pacific Society of Infection Control launched the Infection Prevention and Control Guidelines in July 2022. This document describes the guidelines and recommendations for safe practices in dental setting. It aims to highlight practical recommendations in a concise format designed to assist dental facilities at Asia Pacific region in achieving high standards in infection prevention and control practices, staff and patient safety. METHOD: The guidelines were developed by an appointed workgroup comprising experts in the Asia Pacific region, following reviews of previously published international guidelines and recommendations relevant to each section. RESULTS: It recommends standard precautions as a minimal set of preventive measures to protect staff and prevent cross transmission. Surgical aseptic technique is recommended when procedures are technically complex and longer in duration. Only trained staff are eligible to conduct reprocessing of dental instruments. The design, layout of the dental facility are important factors for successful infection prevention. The facility should also have a Pandemic Preparedness Plan. CONCLUSIONS: Dental facilities should aim for excellence in infection prevention and control practices as this is part of patient safety. The guidelines that come with a checklist help dental facilities to identify gaps for improvement to reach this goal.


Assuntos
Controle de Infecções , Segurança do Paciente , Humanos , Controle de Infecções/métodos , Ásia
11.
Phys Rev Lett ; 108(18): 181805, 2012 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-22681060

RESUMO

Motivated by evidence for the existence of dark matter, many new physics models predict the pair production of new particles, followed by the decays into two invisible particles, leading to a momentum imbalance in the visible system. For the cases where all four components of the vector sum of the two "missing" momenta are measured from the momentum imbalance, we present analytic solutions of the final state system in terms of measurable momenta, with the mass shell constraints taken into account. We then introduce new variables which allow the masses involved in the new physics process, including that of the dark matter particles, to be extracted efficiently. These are compared with a selection of variables in the literature, and possible applications at lepton and hadron colliders are discussed.

12.
Eur Phys J C Part Fields ; 79(1): 39, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30872967

RESUMO

We present results of the updated SuperChic 3 Monte Carlo event generator for central exclusive production. This extends the previous treatment of proton-proton collisions to include heavy ion (pA and AA) beams, for both photon and QCD-initiated production, the first time such a unified treatment of exclusive processes has been presented in a single generator. To achieve this we have developed a theory of the gap survival factor in heavy ion collisions, which allows us to derive some straightforward results about the A scaling of the corresponding cross sections. We compare against the recent ATLAS and CMS measurements of light-by-light scattering at the LHC, in lead-lead collisions. We find that the background from QCD-initiated production is expected to be very small, in contrast to some earlier estimates. We also present results from new photon-initiated processes that can now be generated, namely the production of axion-like particles, monopole pairs and monopolium, top quark pair production, and the inclusion of W loops in light-by-light scattering.

13.
Eur Phys J C Part Fields ; 78(3): 248, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30996657

RESUMO

We investigate the impact of the high precision ATLAS and CMS 7 TeV measurements of inclusive jet production on the MMHT global PDF analysis at next-to-next-to-leading order (NNLO). This is made possible by the recent completion of the long-term project to calculate the NNLO corrections to the hard cross section. We find that a good description of the ATLAS data is not possible with the default treatment of experimental systematic errors, and propose a simplified solution that retains the dominant physical information of the data. We then investigate the fit quality and the impact on the gluon PDF central value and uncertainty when the ATLAS and CMS data are included in a MMHT fit. We consider both common choices for the factorization and renormalization scale, namely the inclusive jet transverse momentum, p ⊥ , and the leading jet p ⊥ , as well as the different jet radii for which the ATLAS and CMS data are made available. We find that the impact of these data on the gluon is relatively insensitive to these inputs, in particular the scale choice, while the inclusion of NNLO corrections tends to improve the data description somewhat and has a qualitatively similar though not identical impact on the gluon in comparison to NLO.

14.
Oncogene ; 37(1): 18-27, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-28869597

RESUMO

Mice lacking genes involving in the DNA-damage response (DDR) are often tumor prone owing to genome instability caused by oncogenic challenges. Previous studies demonstrate that activating transcription factor 3 (ATF3), a common stress sensor, can activate the tumor suppressor p53 and regulate expression of p53 target genes upon DNA damage. However, whether ATF3 contributes to the maintenance of genome stability and tumor suppression remains unknown. Here we report that Atf3-deficient (Atf3-/-) mice developed spontaneous tumors, and died significantly earlier than wild-type (Atf3+/+) mice. Consistent with these results, Atf3-/- mouse embryonic fibroblasts (MEFs) had more aberrant chromosomes and micronuclei, and were genetically unstable. Whereas we demonstrated that ATF3 activated p53 and promoted its pro-apoptotic activity in mouse thymi and small intestines, the chromosomal instability caused by Atf3 deficiency was largely dependent on the regulation of p53 by ATF3. Interestingly, loss of Atf3 also promoted spontaneous tumorigenesis in Trp53+/- mice, but did not affect tumor formation in Trp53-/- mice. Our results thus provide the first genetic evidence linking ATF3 to the suppression of the early development of cancer, and underscore the importance of ATF3 in the maintenance of genome integrity.


Assuntos
Fator 3 Ativador da Transcrição/metabolismo , Carcinogênese/genética , Predisposição Genética para Doença , Instabilidade Genômica , Neoplasias/genética , Fator 3 Ativador da Transcrição/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Aberrações Cromossômicas , Dano ao DNA , Feminino , Fibroblastos , Genes Supressores de Tumor , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias/mortalidade , Neoplasias/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
15.
Appl Clin Inform ; 9(1): 54-61, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29365340

RESUMO

BACKGROUND: In 2015, the German Federal Ministry of Education and Research initiated a large data integration and data sharing research initiative to improve the reuse of data from patient care and translational research. The Observational Medical Outcomes Partnership (OMOP) common data model and the Observational Health Data Sciences and Informatics (OHDSI) tools could be used as a core element in this initiative for harmonizing the terminologies used as well as facilitating the federation of research analyses across institutions. OBJECTIVE: To realize an OMOP/OHDSI-based pilot implementation within a consortium of eight German university hospitals, evaluate the applicability to support data harmonization and sharing among them, and identify potential enhancement requirements. METHODS: The vocabularies and terminological mapping required for importing the fact data were prepared, and the process for importing the data from the source files was designed. For eight German university hospitals, a virtual machine preconfigured with the OMOP database and the OHDSI tools as well as the jobs to import the data and conduct the analysis was provided. Last, a federated/distributed query to test the approach was executed. RESULTS: While the mapping of ICD-10 German Modification succeeded with a rate of 98.8% of all terms for diagnoses, the procedures could not be mapped and hence an extension to the OMOP standard terminologies had to be made.Overall, the data of 3 million inpatients with approximately 26 million conditions, 21 million procedures, and 23 million observations have been imported.A federated query to identify a cohort of colorectal cancer patients was successfully executed and yielded 16,701 patient cases visualized in a Sunburst plot. CONCLUSION: OMOP/OHDSI is a viable open source solution for data integration in a German research consortium. Once the terminology problems can be solved, researchers can build on an active community for further development.


Assuntos
Comportamento Cooperativo , Implementação de Plano de Saúde , Hospitais Universitários , Avaliação de Resultados em Cuidados de Saúde , Alemanha , Humanos , Inquéritos e Questionários , Vocabulário
16.
J Clin Invest ; 76(6): 2191-5, 1985 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3001146

RESUMO

The primary genetic defect in the lysosomal storage disease mucolipidosis III (ML III) is in the enzyme uridine diphospho-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase. This enzyme has two well-defined functions: specific recognition of lysosomal enzymes (recognition function) and phosphorylation of their oligosaccharides (catalytic function). Using fibroblasts from patients with ML III as the source of enzyme, and alpha-methylmannoside and two lysosomal enzymes as the substrates, we have identified defects in both of these functions. In one group of fibroblasts, the catalytic activity of the N-acetylglucosaminylphosphotransferase is decreased while the ability to recognize lysosomal enzymes as specific substrates remains intact. In the second group of fibroblasts, the ability to recognize lysosomal enzymes is impaired while the catalytic activity of the enzyme is normal. These data provide a biochemical rationale for the previously described genetic heterogeneity among patients with ML III (Honey, N. K., O. T. Mueller, L. E. Little, A. L. Miller, and T. B. Shows, 1982, Proc. Natl. Acad. Sci. USA., 79:7420-7424).


Assuntos
Lisossomos/enzimologia , Mucolipidoses/enzimologia , Fosfotransferases/metabolismo , Transferases (Outros Grupos de Fosfato Substituídos) , Fosfatase Ácida , Catepsina D/metabolismo , Células Cultivadas , Humanos , Isoenzimas , Cinética , Metaloproteínas/metabolismo , Metilmanosídeos/metabolismo , Fosforilação , Especificidade por Substrato , Fosfatase Ácida Resistente a Tartarato
17.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 29(4): 534-536, 2017 May 05.
Artigo em Zh | MEDLINE | ID: mdl-29508602

RESUMO

This paper reports the diagnosis and treatment of 2 cases of acute schistosomiasis with ectopic lesion in the lung. It suggests that in schistosomiasis endemic areas, if the patients with the contact history of infested water have the symptom of fever, while the effects of anti-infection and the corresponding treatments are not good, the clinician should consider acute schistosomiasis.


Assuntos
Pulmão/parasitologia , Esquistossomose/diagnóstico , Humanos , Esquistossomose/patologia , Esquistossomose/terapia
18.
Cancer Res ; 58(12): 2612-7, 1998 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-9635587

RESUMO

Because intact IgG has limitations as a tumor-imaging agent, radiolabeled Fv fragments are being evaluated. Due to the high renal accumulation of Fv fragments, methods to block renal uptake are being sought. This study evaluated how well Aminosyn II, a Food and Drug Administration-approved 15% amino acid solution, would block the renal accumulation of 18F anti-Tac disulfide-stabilized Fv (dsFv) fragments (small fragments with high renal uptake). The anti-Tac dsFv is directed against the alpha subunit of the interleukin 2 receptor. It was labeled at specific activities of 1.1-2.7 mCi/mg using N-succinimidyl 4-[18F]fluoromethyl benzoate. Four adult baboons were injected i.v. with 0.7-1.9 mCi and 150 microg of dsFv. Each baboon was preinjected with Aminosyn II i.v. and, on a separate occasion, with a control solution. Thirty min before injection of 18F-labeled anti-Tac dsFv, a bolus of either solution was given, followed by a constant infusion of 13.3 ml/kg/h. Quantitative positron emission tomography imaging was performed. The amino acid levels in serum were measured serially. The baseline levels of lysine (and other amino acids) in plasma were not significantly different in either the Aminosyn II or control infusion group and did not change during the control infusion. In the Aminosyn II group, lysine levels in plasma 5 min before anti-Tac dsFv infusion were 5-15 times higher than the baseline value and continued to rise during the infusion. The areas under the curve in blood of the 18F-labeled anti-Tac dsFv, from time of injection to end of imaging, expressed as percentage injected dose (%ID), were 28.94 +/- 4.05%ID x h/liter (mean +/- SD) for the control group and 32.09 +/- 11.15%ID x h/liter for the Aminosyn II group (P = 0.54). The peak concentration of 18F-labeled anti-Tac dsFv in the kidney of the controls was 24.53 +/- 4.34%ID; the value in the Aminosyn II group was 5.39 +/- 1.89%ID, representing a mean decrease of 78.5%. The times to reach 90% of the peak levels of 18F in the kidney were 5.6 +/- 3.0 min for the Aminosyn II group and 33.8 +/- 4.8 min for the control group. The amounts excreted in urine by 90 min were 47.7 +/- 8.55%ID and 78.5 +/- 12.8%ID (P = 0.01) for the controls and Aminosyn II group, respectively. In conclusion, Aminosyn II effectively blocks the renal accumulation of 18F-labeled anti-Tac dsFv. Use of Aminosyn II should allow much higher tracer administration for the same radiation exposure to the target organ (kidney).


Assuntos
Aminoácidos/farmacologia , Fragmentos de Imunoglobulinas/metabolismo , Região Variável de Imunoglobulina/metabolismo , Rim/metabolismo , Animais , Feminino , Rim/efeitos dos fármacos , Masculino , Papio , Fatores de Tempo , Distribuição Tecidual
19.
Cancer Res ; 55(22): 5323-9, 1995 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-7585595

RESUMO

We evaluated the biodistribution, pharmacokinetics, and generation of catabolites of an 18F- and 125I-labeled anti-Tac disulfide-stabilized Fv fragment (dsFv) in tumor-bearing nude mice. This dsFv is genetically engineered from a murine monoclonal antibody that recognizes the alpha subunit of the interleukin 2 (IL-2 alpha) receptor. Labeling was performed with 18F using N-succinimidyl 4-([18F]fluoromethyl)benzoate or with 125I using the Iodo-Gen method. The immunoreactivities of the radiolabeled anti-Tac dsFv were > 82%. The biodistribution was evaluated (at 15, 45, and 90 min and 6 h) in athymic nude mice (approximately five/group) bearing s.c. tumor xenografts. Cell line A431 served as the IL-2 receptor-negative control tumor, whereas the ATAC4 cell line served as our IL-2 receptor-positive tumor. Animals received injections of 18F-labeled anti-Tac dsFv (0.7-1.4 megabecquerels/1.5-3 micrograms) and 125I-labeled anti-Tac dsFv (0.1-0.4 megabecquerels/0.9-1 microgram). Blood clearance for both preparations was rapid, with < 10% retained in the blood by 15 min. Maximum accumulation in ATAC4 tumors occurred between 45 and 90 min and peaked at a mean of 4.2% injected dose/g (18F) and 5.6% of injected dose/g (125I). At 6 h, the ATAC4 tumors contained 11 times more 18F and 3 times more 125I than did the A431 tumors. The ATAC4 tumor:blood ratios for the 18F and 125I were > 12:1 and > 1.4:1 at 6 h, respectively, whereas the ratios for the antigen-negative A431 tumor were less than 1. The kidneys were the major route of elimination. Catabolites appeared quickly and were identified as [125I]iodide and predominantly N-epsilon-[18F]4-fluoromethylbenzoyl(alpha-N-acetyl) lysine. This is the first study to evaluate the biodistribution of an 18F-labeled Fv fragment in vitro and in vivo. In vivo, the dsFv was taken up rapidly by the kidneys, producing lysine-containing catabolites for 18F-labeled dsFv and [125I]iodide for 125I-labeled dsFv.


Assuntos
Anticorpos Monoclonais/farmacocinética , Fragmentos de Imunoglobulinas/metabolismo , Receptores de Interleucina-2/imunologia , Animais , Feminino , Radioisótopos de Flúor , Humanos , Radioisótopos do Iodo , Camundongos , Camundongos Nus , Controle de Qualidade , Radioimunodetecção , Receptores de Interleucina-2/análise , Distribuição Tecidual , Células Tumorais Cultivadas
20.
Artigo em Inglês | MEDLINE | ID: mdl-26855605

RESUMO

We investigate the variation in the MMHT2014 PDFs when we allow the heavy-quark masses [Formula: see text] and [Formula: see text] to vary away from their default values. We make PDF sets available in steps of [Formula: see text] and [Formula: see text], and present the variation in the PDFs and in the predictions. We examine the comparison to the HERA data on charm and beauty structure functions and note that in each case the heavy-quark data, and the inclusive data, have a slight preference for lower masses than our default values. We provide PDF sets with three and four active quark flavours, as well as the standard value of five flavours. We use the pole mass definition of the quark masses, as in the default MMHT2014 analysis, but briefly comment on the [Formula: see text] definition.

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