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1.
Graefes Arch Clin Exp Ophthalmol ; 254(10): 2005-2009, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27549579

RESUMO

PURPOSE: To evaluate the objective and subjective outcome after phototherapeutic keratectomy (PTK) on recurrent corneal erosions (Hamburg protocol). METHODS: For the standardized PTK according to Hamburg protocol a manual abrasio corneae performed with 20 % alcohol is followed by an excimer ablation depth of ≥15 µm (group1 15 µm; group 2 > 15 µm ablation depth) and 7 mm optical zone. All patients (N = 48) were invited for follow-up examinations and the evaluation of changes concerning subjective symptoms. RESULTS: A significantly reduced subjective impairment of night vision, significantly less pain and less foreign body sensations (for all p < 0.05) were noted in 48 patients that met the inclusion criteria (26 women, 22 men). In the follow-up period an improvement of corrected distance visual acuities (cdva) from 0.80 to 1.08 (group 1) and from 0.58 to 0.99 (group 2) was demonstrated. CONCLUSION: PTK (Hamburg Schema) is a safe and effective procedure to reduce subjective symptoms and improve discomfort in recurrent corneal erosion.


Assuntos
Doenças da Córnea/diagnóstico , Doenças da Córnea/cirurgia , Lasers de Excimer/uso terapêutico , Ceratectomia Fotorrefrativa/métodos , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Acuidade Visual/fisiologia
2.
Klin Monbl Augenheilkd ; 231(6): 636-9, 2014 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-24788604

RESUMO

This case report describes a patient with keratoconus and neurodermitis suffering from a significantly prolonged postoperative time interval to re-epithelisation after corneal cross-linking. The development of corneal calcifications and vascularisations additionally inhibited proper re-epithelisation. Therefore the patient received four subsequent subconjunctival injections of Bevacizumab and an additional keratectomy to remove the calcifications. This therapeutic scheme led to a significant reduction of corneal vascularisation and finally a full rehabilitation of the epithelium.


Assuntos
Neovascularização da Córnea/induzido quimicamente , Neovascularização da Córnea/fisiopatologia , Reagentes de Ligações Cruzadas/efeitos adversos , Reagentes de Ligações Cruzadas/uso terapêutico , Ceratocone/terapia , Neurodermatite/complicações , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/fisiopatologia , Reepitelização/efeitos dos fármacos , Reepitelização/fisiologia , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Calcinose/induzido quimicamente , Calcinose/diagnóstico , Calcinose/fisiopatologia , Calcinose/terapia , Terapia Combinada , Neovascularização da Córnea/diagnóstico , Neovascularização da Córnea/terapia , Humanos , Injeções Intraoculares , Ceratocone/diagnóstico , Masculino , Neurodermatite/diagnóstico , Ceratectomia Fotorrefrativa , Complicações Pós-Operatórias/terapia , Riboflavina , Lâmpada de Fenda
3.
Klin Monbl Augenheilkd ; 230(6): 595-603, 2013 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-23794429

RESUMO

Concomitant with new innovations in the field of refractive surgery, therapeutic excimer laser applications like phototherapeutic keratectomy (PTK) and topography-guided customised ablation treatment are gaining high importance and undergoing rapid evolution. Nowadays, PTK is an effective treatment modality for superficial corneal pathologies. Primary indications are decreased epithelial adherence, superficial opacifications and an irregular corneal surface. For the right indication and successful treatment of corneal pathologies with PTK, a knowledge of the size, depth and nature of the pathology, as well as the refractive status of both eyes is important. Next to slit-lamp examination, objective measuring systems like the topography, confocal microscopy and the anterior segment OCT facilitate presurgical planning. Regarding the treatment procedure the surgeon can choose between a variety of methods. PTK can be combined with manual epithelial debridement or done by only using the excimer laser. In the case of an irregular corneal surface, depending on the pathology, masking fluids or topography-guided custom ablation protocols can increase the visual outcome. To avoid recurrence of the underlying pathology (e.g., corneal dystrophy, haze), the topical application of 0.02% mitomycin C for 20-60 seconds has proved to be a safe and effective procedure. If the surgeon considers all the patient-related factors carefully and manages to combine the available treatment options correctly, PTK embodies an effective and minimally invasive alternative to lamellar or penetrating keratoplasty.


Assuntos
Córnea/cirurgia , Terapia a Laser/métodos , Lasers de Excimer/uso terapêutico , Fototerapia/métodos , Erros de Refração/diagnóstico , Erros de Refração/terapia , Procedimentos Cirúrgicos Refrativos/métodos , Humanos , Cuidados Pré-Operatórios/métodos
4.
Klin Monbl Augenheilkd ; 228(6): 531-6, 2011 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-21108166

RESUMO

LASIK has become the preferred surgical procedure for the correction of refractive errors. Microbial keratitis is a rare but severe complication. The incidence of post-LASIK keratitis, (uni- and bilateral) is difficult to estimate. The risk of bilateral infection could until now only be approximated by calculating it from the risk of unilateral infection. Due to the fortunately low incidence of post-LASIK keratitis, large-scale studies are necessary to obtain valid statistical data. The American Society of Cataract and Refractive surgery (ASCRS) developed a post-LASIK infectious keratitis survey in 2001. 116 post-LASIK infections were reported by the members of the society. The calculated incidence was 0.035 % or 1 infection in every 2919 procedures. Llovet et al. found 9 patients (18 eyes) with bilateral post-LASIK keratitis out of 204 586 procedures (incidence 0.0084 %). Gram-positive bacteria and atypical mycobacteria are the most common causes for microbial post-LASIK keratitis. There is an increasing literature of post-LASIK case reports caused by rare or atypical species. Severe cases of keratitis are more often correlated with a prolonged onset of infection and caused by atypical species. An overview of the current literature and our own data regarding post-LASIK keratitis (uni-, and bilateral) are presented.


Assuntos
Ceratite/epidemiologia , Ceratite/cirurgia , Ceratomileuse Assistida por Excimer Laser In Situ/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Comorbidade , Humanos , Incidência , Medição de Risco
5.
Ophthalmologe ; 116(7): 677-681, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-30684006

RESUMO

According to the literature there are a large number of potential systemic contraindications for corneal refractive surgery. In cases with relative contraindications, surgery should be performed only after weighing up the individual risks and under controlled disease conditions; however, the "evidence" for many of these contraindications is based only on case reports or series, expert opinions or known complications in non-laser-assisted eye surgery. Randomized clinical trials are therefore required.


Assuntos
Doenças da Córnea , Ceratomileuse Assistida por Excimer Laser In Situ , Contraindicações , Córnea
6.
Arch Soc Esp Oftalmol (Engl Ed) ; 93(2): 60-68, 2018 Feb.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28651810

RESUMO

PURPOSE: To assess visual outcomes of retreatment after laser in situ keratomileusis (LASIK) by lifting the flap or performing photorefractive keratectomy (PRK) on the flap, as well as to establish whether there was an increased risk of epithelial ingrowth (EIG) when LASIK and lifting of the flap are separated by a long time interval and to determine the incidence of corneal haze after PRK. METHODS: Retrospective study of 4077 patients (5468 eyes) who underwent LASIK and subsequent retreatment were reviewed in order to study their visual results and identify cases of EIG and corneal haze. RESULTS: Enhancements included 5196 eyes from 3876 patients that were retreated by lifting the flap, and 272 eyes from 201 patients that were retreated by PRK on the flap. No statistically significant differences were found between the retreatments in terms of predictability, efficacy, and safety. A total of 704 cases of EIG were found after lifting the flap, for which surgical cleansing was necessary in 70. Surgical cleansing decreased the efficacy index when compared with patients with EIG who did not need cleansing (P=.01). Differences in terms of safety and predictability were not statistically significant. The incidence of corneal haze after ablation of the surface of the previous flap was 14.34%, although none of these cases were clinically relevant. CONCLUSIONS: Visual outcomes were similar between patients who were retreated by lifting the flap and those who underwent PRK. The incidence of EIG when the flap was lifted was 13.55%. The incidence of EIG increases with the time elapsed between the primary procedure and retreatment.


Assuntos
Opacidade da Córnea/epidemiologia , Ceratomileuse Assistida por Excimer Laser In Situ , Ceratectomia Fotorrefrativa , Complicações Pós-Operatórias/epidemiologia , Retalhos Cirúrgicos/cirurgia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retratamento , Estudos Retrospectivos , Adulto Jovem
7.
Ophthalmologe ; 114(8): 722-727, 2017 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-27913863

RESUMO

BACKGROUND: Refractive lens exchange and implantation of a multifocal intraocular lens (MIOL) is mainly advised for ametropes with presbyopia. Non-presbyopic young ametropes who wish spectacle-independence are usually treated with corneal refractive surgery or phakic lenses. OBJECTIVES: This retrospective case series aimed to analyse the refractive and subjective satisfaction outcome after MIOL surgery in both eyes of non-presbyopic ametropes where other treatment options were not possible. MATERIALS AND METHODS: This retrospective case series comprised consecutively treated 32 eyes of 16 patients (5 myopic, 11 hyperopic patients; mean age 31 ± 6 years) who wished spectacle-independence and thus received an aspheric bifocal biconvex refractive-diffractive single-piece MIOL (Acri.Lisa 366/809, Carl Zeiss Meditec AG). Refractive data prior to and after surgery as well as subjective satisfaction at the 1­year follow-up examination were assessed. RESULTS: Related to distance corrected near visual acuity myopic eyes had a median efficacy index (EI) of 0.92 (±0.20) and hyperopes of 0.91 (±0.12) (P = 0.415). For intermediate vision, in both groups a lower EI (<0.5; P = 0.188) resulted in lower subjective satisfaction, which was higher for near and distance vision. Some of hyperopic patients reported limitations in near and distance vision, only one hyperopic patient would not have chosen this surgery again. None had a related complication during the follow-up. CONCLUSIONS: When neither laser refractive surgery nor implantation of a phakic lens is possible, young non-presbyopic ametropes do profit from MIOL surgery with an aspheric bifocal biconvex refractive-diffractive MIOL.


Assuntos
Hiperopia/cirurgia , Lentes Intraoculares Multifocais , Miopia/cirurgia , Adulto , Feminino , Alemanha , Humanos , Masculino , Satisfação do Paciente , Refração Ocular , Estudos Retrospectivos , Acuidade Visual
8.
Thromb Res ; 140 Suppl 1: S193, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27161734

RESUMO

INTRODUCTION: Multiple myeloma (MM) is an incurable, genetically heterogeneous malignancy of plasma cells that secrete non-functioning immunoglobulins and present high proteasome activity. MM is characterized by bone marrow infiltration leading to multiple lytic bone lesions, cytopenia and increased rate of thrombotic events. Microvesicles (MVs) include exosomes (30-100 nm) and microparticles (0.1-1 micron) shed from various cells and expressing antigens reflecting their cellular origin. MVs are involved in thrombosis, inflammation and cancer.However, the effect of MM-MVs on disease progression and their mechanism of action are unclear. We assume that MVs play a role in the interaction between malignant plasma cells and mesenchymal and endothelial cells (EC). AIM: To characterize MM-MVs and investigate their effects on microenvironment cells. MATERIALS AND METHODS: MVs were isolated from MM cell line RPMI 8226 untreated or treated with bortezomib and from peripheral blood (PB) and bone marrow (BM) of MM patients (n=13) and healthy controls (n=14). MM-MV size, concentration and cell origin were measured by Nanosite and FACS. Protein content was evaluated by protein arrays and ELISA. Coagulation and proteasome activity were assessed using chromogenic assays. Migratory capacity (migration assay), proliferative rate (XTT assay) and cell-signaling effects (Western blot analysis) of MVs on BM-mesenchymal and ECs were analyzed. RESULTS: MM cells exhibited high MV shedding rate, which further increased with the exposure to bortezomib. Significant elevation in MV production was found in MM patients compared to controls. MM-MVs expressed membrane MM markers (syndecan-1/ CD138, CD38), coagulation factor (TF, TFPI, EPCR, TM) and angiogenic factors (VEGFR1, VEGFR2, and CD31). MM-MVs contained high levels of growth factors (Angiogenin, PDGF-BB and VEGF) and displayed procoagulant and proteasome activity. MM-MVs penetrated cells and affected their function. MVs of untreated cells and patient MVs increased EC and mesenchymal cell migration and EC proliferation, while MVs obtained from bortezomib-treated cells decreased these effects. MVs of untreated cells increased ERK1/2 and c-Jun phosphorylation in ECs (by 6.15 and 1.84 fold) but did not affect MAPKAPK-2. MVs of bortezomib-treated cells reduced c-Jun phosphorylation in ECs. CONCLUSIONS: MM cells are characterized by high shedding rate of MVs. They are pro-coagulants and increase EC thrombogenicity, suggesting their involvement in MM-related thrombosis. MVs contain high levels of angiogenic factors that affect mesenchymal and EC, induce cell migration and proliferation via specific signal transductions. MVs exposed to bortezomib display lower levels of angiogenic factors, which limits proliferation and migration of MVs, reflecting the efficacy of therapy and MM dynamics.

9.
J Gen Physiol ; 109(3): 401-14, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9089445

RESUMO

We used patch clamp techniques to study the inhibitory effects of pentobarbital and barbital on nicotinic acetylcholine receptor channels from BC3H-1 cells. Single channel recording from outside-out patches reveals that both drugs cause acetylcholine-activated channel events to occur in bursts. The mean duration of gaps within bursts in 2 ms for 0.1 mM pentobarbital and 0.05 ms for 1 mM barbital. In addition, 1 mM barbital reduces the apparent single channel current by 15%. Both barbiturates decrease the duration of openings within a burst but have only a small effect on the burst duration. Macroscopic currents were activated by rapid perfusion of 300 microM acetylcholine to outside-out patches. The concentration dependence of peak current inhibition was fit with a Hill function; for pentobarbital, Ki = 32 microM, n = 1.09; for barbital, Ki = 1900 microM, n = 1.24. Inhibition is voltage independent. The kinetics of inhibition by pentobarbital are at least 30 times faster than inhibition by barbital (3 ms vs. < 0.1 ms at the Ki). Pentobarbital binds > or = 10-fold more tightly to open channels than to closed channels; we could not determine whether the binding of barbital is state dependent. Experiments performed with both barbiturates reveal that they do not compete for a single binding site on the acetylcholine receptor channel protein, but the binding of one barbiturate destabilizes the binding of the other. These results support a kinetic model in which barbiturates bind to both open and closed states of the AChR and block the flow of ions through the channel. An additional, lower-affinity binding site for pentobarbital may explain the effects seen at > 100 microM pentobarbital.


Assuntos
Hipnóticos e Sedativos/farmacologia , Antagonistas Nicotínicos/farmacologia , Receptores Nicotínicos/efeitos dos fármacos , Animais , Barbital/farmacocinética , Barbital/farmacologia , Sítios de Ligação , Ligação Competitiva/efeitos dos fármacos , Linhagem Celular , Estimulação Elétrica , Hipnóticos e Sedativos/farmacocinética , Potenciais da Membrana/fisiologia , Camundongos , Técnicas de Patch-Clamp , Pentobarbital/farmacocinética , Pentobarbital/farmacologia , Ligação Proteica
10.
Ophthalmologe ; 112(9): 740-5, 2015 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-25666571

RESUMO

BACKGROUND: Corneal refractive surgery alters the biomechanical properties of the cornea. OBJECTIVES: This study was initiated to evaluate corneal biomechanical parameters after LASIK using a Corvis® ST tonometer (CST). METHODS: This retrospective study included 51 eyes of 32 myopic patients. All CST measurements were performed 1 day before surgery and at the 1-month follow-up examination. The LASIK procedure included mechanical flap preparation using a Moria SBK microkeratome and an Allegretto excimer laser platform. RESULTS: Statistically significant differences were observed for mean second applanation length, mean first and second deflection lengths, mean first and second deflection amplitudes, peak distance and radius of curvature. Statistically significant positive correlations were found between the change (Δ) in radius of curvature and Δ in manifest refraction spherical equivalent (MRSE), between the ablation depth and the Δ in intraocular pressure. Applying multiple regression models also revealed statistically significant differences in parameters obtained by CST measurements. CONCLUSION: Several CST parameters were statistically significantly altered by LASIK thereby indicating that flap creation, ablation or both, significantly change the ability of the cornea to absorb or dissipate energy.


Assuntos
Córnea/fisiopatologia , Córnea/cirurgia , Pressão Intraocular , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Miopia/fisiopatologia , Tonometria Ocular/instrumentação , Adulto , Topografia da Córnea/instrumentação , Módulo de Elasticidade , Feminino , Humanos , Masculino , Miopia/cirurgia , Estudos Retrospectivos , Estresse Mecânico , Resultado do Tratamento
11.
Ophthalmologe ; 112(9): 770-7, 2015 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-25501931

RESUMO

BACKGROUND: Analyses regarding accuracy and reproducibility of intraocular pressure (IOP) measurements and pachymetry with corneal visualization Scheimpflug technology (Corvis ST®, CST). MATERIAL UND METHODS: Retrospective analysis of 72 eyes with primary open angle glaucoma (POAG) and ocular hypertension (OHT) with no prior surgery or other pathology. The results of Goldmann applanation tonometry (GAT), non-contact tonometry (NCT) and ultrasound pachymetry (USP) were compared with repeat measurements with CST. For statistical analyses the t-test and Bland-Altman plots were applied. RESULTS: The mean IOP was 15.5 ± 4.4 mmHg (CST), 14.8 ± 4.4 mmHg (GAT) and 15.6 ± 4.8 mmHg (NCT). The results of GAT and CST as well as GAT and NCT demonstrated statistically significant differences (p < 0.001) whereas NCT and CST displayed no significant differences in IOP (p = 0.72). The mean differences between the repeat measurements were 0.35 ± 1.7 mmHg (CST) and 0.04 ± 0.85 mmHg (GAT). The mean CST pachymetry results showed 551.3 ± 46.5 µm and the USP 526.5 ± 46.4 µm (p < 0.001). The mean difference between the repeated CST measurements was 24.8 ± 21 µm. No repeat measurement data were available for USP. CONCLUSION: The CST is a new device for simultaneously measuring the IOP, pachymetry and biomechanical properties of the cornea. Whether the deviations in the IOP measured by CST and CST pachymetry from the manually performed gold standard has to be evaluated as deficient, tolerable or maybe as an improvement, has to be evaluated in further studies. Because of the automated and contact-free measurement method as well as the potential for simultaneously analyzing biomechanical properties of the cornea, the CST is a device that might help the quest for measuring the 'true' IOP.


Assuntos
Córnea/fisiopatologia , Paquimetria Corneana/instrumentação , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Pressão Intraocular , Tonometria Ocular/instrumentação , Idoso , Idoso de 80 Anos ou mais , Córnea/patologia , Paquimetria Corneana/métodos , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tonometria Ocular/métodos
12.
Pediatrics ; 101(3 Pt 1): 335-43, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9480994

RESUMO

BACKGROUND: Ritonavir, a potent antiretroviral protease inhibitor, has been approved for the treatment of adults and children with human immunodeficiency virus (HIV) infection. In a phase I/II study, we assessed the safety, tolerability, and pharmacokinetic profile of the oral solution of ritonavir in HIV-infected children and studied the preliminary antiviral and clinical effects. METHODS: HIV-infected children between 6 months and 18 years of age were eligible. Four dose levels of ritonavir oral solution (250, 300, 350, and 400 mg/m given every 12 hours) were evaluated in two age groups (2 years). Ritonavir was administered alone for the first 12 weeks and then in combination with zidovudine and/or didanosine. Clinical and laboratory parameters were monitored every 2 to 4 weeks. RESULTS: A total of 48 children (median age, 7.7 years; range, 0.5 to 14.4 years) were included in this analysis. Dose-related nausea, diarrhea, and abdominal pain were the most common toxicities and resulted in discontinuation of ritonavir in 7 children. Ritonavir was well absorbed at all dose levels, and plasma concentrations reached a peak 2 to 4 hours after a dose. CD4 cells counts increased by a median of 79 cells/mm3 after 4 weeks of monotherapy and were maintained throughout the study. Plasma HIV RNA decreased by 1 to 2 log10 copies/mL within 4 to 8 weeks of ritonavir monotherapy, and this level was sustained in patients enrolled at the highest dose level of 400 mg/m for the 24-week period. CONCLUSIONS: The oral solution of ritonavir has potent antiretroviral activity as a single agent and is relatively well tolerated by children when administered alone or in combination with zidovudine or didanosine.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Ritonavir/uso terapêutico , Administração Oral , Adolescente , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Didanosina/uso terapêutico , Quimioterapia Combinada , Feminino , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/farmacocinética , Humanos , Lactente , Masculino , Ritonavir/efeitos adversos , Ritonavir/farmacocinética , Carga Viral , Zidovudina/uso terapêutico
13.
Cancer Lett ; 116(2): 167-75, 1997 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-9215860

RESUMO

Degradation of DNA produces deoxycytidine. Metabolism of deoxycytidine to dCTP inhibits phosphorylation of cytosine arabinoside (araC), fludarabine (FaraA) and 2-chlorodeoxyadenosine (CdA) by deoxycytidine kinase. This study measured plasma deoxycytidine in healthy adults and two leukemia patients and then determined how clinically relevant deoxycytidine levels would affect drug toxicity in human leukemia and lymphoma cells. Deoxycytidine was well below 0.05 microM in ten healthy persons. In the leukemia patients it was <0.05 and 0.44 microM before chemotherapy, rising to 10.3 and 5.5 microM during treatment. A broad range of clinically relevant deoxycytidine levels were high enough to profoundly decrease araC, FaraA and CdA toxicity in MOLT3, CA46 and HL60 leukemia/lymphoma cells and to change dCTP, DNA synthesis and drug incorporation into DNA in a manner consistent with prior mechanistic studies. Varying deoxycytidine levels could be an important factor influencing leukemia therapy.


Assuntos
Desoxicitidina/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Cladribina/metabolismo , Cladribina/toxicidade , Citarabina/metabolismo , Citarabina/toxicidade , Nucleotídeos de Desoxicitosina/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Vidarabina/análogos & derivados , Vidarabina/metabolismo , Vidarabina/toxicidade
14.
Leuk Res ; 17(2): 167-74, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8429693

RESUMO

Thymidine kills cells by depleting dCTP stores. The present experiments tested whether deoxycytidine, by replenishing dCTP pools, could prevent thymidine cytotoxicity and thymidine's enhancement of carboplatin killing in two human T-cell acute leukemia cell lines. MOLT3 and JM cells were exposed to combinations of thymidine, deoxycytidine, and carboplatin and then assessed for survival, the magnitude of thymidine-carboplatin chemosensitization, and changes in deoxyribonucleoside triphosphate pools. For both cell lines, deoxycytidine (up to 144.5 micrograms/ml x 24 h) completely restored dCTP pools but only partially protected against thymidine cytotoxicity (100-1000 micrograms/ml x 24 h) and thymidine-carboplatin sensitization (up to 60 micrograms carboplatin/ml during the last hour of thymidine). This contrasts with complete protection in prior studies using other cell types. Thymidine alone markedly increased dTTP and dGTP pools and decreased dCTP; dATP pools underwent a sharp decline which has not been observed before in any cell line. In subsequent studies 0.0336-137.3 micrograms deoxyadenosine/ml partially prevented cytotoxicity and carboplatin sensitization by 300 micrograms thymidine/ml. Together, deoxycytidine and deoxyadenosine completely prevented thymidine-carboplatin sensitization even though dATP and dCTP pools were not entirely returned to normal. These findings are discussed in regard to the unusual sensitivity of T-cell malignancies to thymidine toxicity, mechanisms of cytotoxicity and chemosensitization by thymidine, and the possibility of thymidine selectively sensitizing T-cell malignancies to killing by alkylating agents.


Assuntos
Desoxirribonucleotídeos/metabolismo , Leucemia de Células T/metabolismo , Timidina/toxicidade , Carboplatina/administração & dosagem , Desoxiadenosinas/metabolismo , Desoxicitidina/metabolismo , Humanos , Leucemia de Células T/patologia , Timidina/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacos
15.
Bone Marrow Transplant ; 26(11): 1221-3, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11149735

RESUMO

A 10-year-old girl with Fanconi anemia and severe aplastic anemia underwent a haploidentical BMT from her mother due to lack of a matched family donor. T cell depletion was done by positive selection of CD34 cells with immunomagnetic beads. Due to graft rejection a second haploidentical BMT from the father was successfully undertaken. No immunosuppression was given after the transplant. Immunological reconstitution took approximately 6 months, with no GVHD or severe infections. Such a transplant, containing a large purified CD34 cell fraction with a minimal number of added T cells, should be considered as the treatment of choice for patients with Fanconi anemia if no HLA matched donor is available.


Assuntos
Transplante de Medula Óssea , Anemia de Fanconi/terapia , Antígenos CD34/imunologia , Transplante de Medula Óssea/imunologia , Transplante de Medula Óssea/métodos , Criança , Pai , Feminino , Antígenos HLA/genética , Antígenos HLA/imunologia , Haplótipos , Humanos , Separação Imunomagnética , Doadores Vivos , Depleção Linfocítica , Linfócitos T/imunologia
16.
Clin Ther ; 24(12): 2051-63, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12581544

RESUMO

BACKGROUND: Studies have suggested that nonspecific nonsteroidal anti-inflammatory drugs may inhibit matrix biosynthesis by articular cartilage, thereby accelerating the progression of osteoarthritis (OA). OBJECTIVE: The objective of this analysis was to determine whether 1-year treatment with the cyclooxygenase-2-specific inhibitor celecoxib at up to twice the recommended and maximally effective dose for OA had any deleterious effects on OA progression by assessing radiographic changes in knee or hip joint morphology in patients with OA. METHODS: In a 12-month, multicenter, prospective, open-label trial, patients with OA of the knee or hip or rheumatoid arthritis received celecoxib at doses ranging from that recommended for the treatment of OA (200 mg/d) to twice the recommended daily dosage (400 mg/d). Available radiographs showing baseline and end-of-treatment status were analyzed using semiquantitative measures of index joint morphology in patients with mild to moderate OA. The morphologic scores were then subjected to mean change and shift-table analysis to determine the extent and rate of disease progression. RESULTS: A total of 2,327 patients (796 with OA of the knee, 1,531 with OA of the hip) were included. A subset of 344 patients (160 with OA of the knee, 184 with OA of the hip) had radiographs from both before and after 12 months' celecoxib treatment. One hundred forty-seven and 158 pairs of knee and hip radiographs, respectively, were available for analysis. These revealed that, with the exception of significant hip joint-space narrowing (P = 0.029), no evidence of disease progression with long-term celecoxib treatment could be detected. The observed increase in hip joint-space narrowing was small (0.14 units/y) (95% CI, 0.08-0.20), was observed prior to celecoxib exposure (by mean change or shift-table analysis), and was not dose related. CONCLUSION: These results are consistent with the hypothesis that long-term therapy with celecoxib does not accelerate progression of OA of the knee or hip.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Celecoxib , Progressão da Doença , Método Duplo-Cego , Feminino , Quadril/diagnóstico por imagem , Humanos , Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Estudos Prospectivos , Pirazóis , Radiografia
17.
Physiol Behav ; 32(2): 229-35, 1984 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-6371858

RESUMO

The feeding behavior of rats sympathectomized by neonatal administration of guanethidine (GUA) and/or adult adrenal demedullation (MDL) was investigated. GUA treatment tended to decrease body weight gain and food intake, chiefly by decreasing meal size and increasing satiety ratios. It also attenuated the increase in food intake caused by 2-deoxy-D-glucose (2DG; 150, 300, 450 mg/kg, IP) but not by insulin (3, 6, 9 U/kg, IP). MDL altered meal patterns in the same manner as GUA treatment but the effects were of smaller magnitude. It did not influence the response to either glucoprivic challenge. Combined GUA treatment and MDL generally produced additive effects. These results suggest that the major sympathetic influence on feeding is through adrenergic innervation and not circulating catecholamines. The hypothesis that the alteration in feeding patterns produced by ventromedial hypothalamic lesions is due to decreased sympathetic activity was not supported.


Assuntos
Medula Suprarrenal/fisiologia , Comportamento Alimentar/fisiologia , Sistema Nervoso Simpático/fisiologia , Animais , Peso Corporal , Desoxiglucose/farmacologia , Ingestão de Alimentos , Feminino , Glucose/metabolismo , Guanetidina/farmacologia , Insulina/farmacologia , Ratos , Ratos Endogâmicos , Resposta de Saciedade/fisiologia , Simpatectomia Química
18.
J Occup Environ Med ; 43(7): 616-22, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11464392

RESUMO

The goal of occupational safety and health intervention effectiveness research is to determine whether specific interventions work to prevent work-related injury and illness. But that is not the whole story. It is also important that the development and implementation of the intervention be evaluated. All three phases (development, implementation, and effectiveness) are central to a model of intervention research proposed by the National Occupational Research Agenda Intervention Effectiveness Research team. Areas for future research are also presented.


Assuntos
Pesquisa sobre Serviços de Saúde/métodos , Saúde Ocupacional , Avaliação de Processos e Resultados em Cuidados de Saúde/métodos , Coleta de Dados/métodos , Humanos , Modelos Teóricos , National Institute for Occupational Safety and Health, U.S. , Projetos de Pesquisa , Estados Unidos
19.
Am J Sports Med ; 20(3): 347-50, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1636868

RESUMO

Fractures occurring in teenagers during arm wrestling usually involve the distal humerus and appear as a fracture of the medial epicondyle. We studied eight male patients, aged 13 to 15 years, with such fractures. All fractures involved the right hand and occurred while the patients were in the final stages of winning a match in a formal competition. Three fractures occurred during an official competition and the other five occurred during a match between friends. One patient suffered from ulnar nerve paresis that eventually recovered spontaneously. All of the patients were immobilized for 10 to 21 days, and progressed gradually to motion of the elbow. At 1-year followup, clinical and functional results were satisfying. Therefore, we recommend conservative management for fractures of the medial epicondyle sustained during arm wrestling.


Assuntos
Fraturas Ósseas/etiologia , Úmero/lesões , Luta Romana/lesões , Adolescente , Braço , Seguimentos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/terapia , Humanos , Imobilização , Masculino , Radiografia , Amplitude de Movimento Articular/fisiologia , Nervo Ulnar/lesões
20.
J Reprod Med ; 46(1): 34-8, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11209629

RESUMO

OBJECTIVE: To determine women's awareness and level of understanding of the risks and sequelae of sexually transmitted diseases (STDs). STUDY DESIGN: The study was a cross-sectional survey of 103 women seen at an urban center. We recruited women from several clinical sites: (1) patients with signs or symptoms of an STD seen in a busy women's urgent care unit, (2) women enrolled in clinical studies for STDs or bacterial vaginosis, (3) patients admitted to the hospital and found to have an STD, and (4) women at high risk based on age and sexual activity. A trained female interviewer administered the survey to women agreeing to participate. The questionnaire assessed the patient's awareness of various STDs and their association with adverse outcomes. The survey also evaluated women's knowledge regarding STD prevention. Descriptive analyses were performed using SAS (Cary, North Carolina) on the 103 patients surveyed. RESULTS: The median age of our survey population was 23, 66% were nonwhite, and 37% were on public assistance or uninsured. The population was at high risk for STDs based on the reported history of infection with Neisseria gonorrhoeae and Chlamydia trachomatis (6% and 38%, respectively). Of the 103 women surveyed, 33% had never heard of pelvic inflammatory disease (PID), and 79.6% could not identify any adverse sequelae of PID. Sixty-five percent were unaware that PID increases the risk of ectopic pregnancy, and 56.3% were unaware that it could result in chronic pelvic pain. When asked if they knew of any methods to prevent or reduce their risk of STDs, only 18% mentioned barrier contraception (condoms). Over 57% of respondents could not name a way to prevent STDs. CONCLUSION: Increased educational efforts targeted at high-risk individuals are necessary to improve knowledge of STDs and their adverse sequelae. With greater knowledge and awareness, individuals and couples may be more likely to practice protective behaviors, such as reducing high-risk exposure, and to increase preventive measures, such as barrier contraception use.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Infecções Sexualmente Transmissíveis/complicações , Adolescente , Adulto , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis , Preservativos , Estudos Transversais , Feminino , Gonorreia/epidemiologia , Educação em Saúde , Humanos , Renda , Pessoas sem Cobertura de Seguro de Saúde , Doença Inflamatória Pélvica/epidemiologia , Doença Inflamatória Pélvica/microbiologia , Dor Pélvica , Gravidez , Gravidez Ectópica/microbiologia , Grupos Raciais , Fatores de Risco , Comportamento Sexual , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/prevenção & controle , Inquéritos e Questionários
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