RESUMO
BACKGROUND: Radiation therapy and chemoradiation therapy play a major role in the definitive management of esophageal cancer. Survival in esophageal cancer patients is still relatively poor, mostly due to high rates of local recurrence and distant metastases. It is hypothesized that dose escalation in radiotherapy could improve outcomes. Therefore, this retrospective analysis aimed to investigate the outcomes and toxicity in patients treated with local dose escalation by means of using simultaneous integrated boost concepts. METHODS: Between 2012 and 2018, 101 patients with esophageal carcinoma were analyzed in this monocentric, retrospective study. All patients received definitive chemoradiation or radiation therapy alone as intensity modulated radiotherapy. The prescribed dose was 50.4 Gy in 28 fractions to the primary tumor and the elective lymph nodes as well as a simultaneous integrated boost (SIB) with 58.8 Gy to macroscopic tumor and lymph node metastases. Endpoints were overall survival (OS), progression free survival (PFS), local control rate (LCR) and toxicity. RESULTS: 60 patients (59.4%) received chemoradiation, 41 patients (40.6%) radiotherapy alone. The median follow up was 17 months (range 0-75 months). OS, PFS and LCR were at 63.9%, 53.9% and 59.9% after 1 year and 37.6%, 34.5% and 36.1%, respectively after 3 years. 16 patients (15.8%) in total developed a locoregional recurrence within the field of radiation. In 48 patients (47.5%) at least one grade III° (CTCAE) toxicity was documented during radiotherapy, mostly dysphagia (36 pat., 75%). One patient suffered from a grade IV° pneumonia. CONCLUSION: This retrospective analysis demonstrates that a SIB concept in definitive (chemo)radiation therapy is safe and feasible, showing acceptable outcomes in this patient cohort. Considering that this cohort mainly consists of elderly patients not eligible for chemotherapy in many cases, we emphasize the aspect of SIB radiation therapy as potential partial compensation for omitted simultaneous chemotherapy. Prospective studies are needed for validation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/mortalidade , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Recidiva Local de Neoplasia/terapia , Radioterapia de Intensidade Modulada/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Adenosine plays a role in the energy supply of cells and provokes differential, hormone-like functions in circulating cells and various tissues. Its release is importantly regulated by oxygen tension. This renders adenosine and its kinetics interesting to investigate in humans subjected to low oxygen conditions. Especially for space exploration scenarios, hypoxic conditions - together with reduced gravity - represent two foreseen living conditions when planning manned long-duration space missions or planetary habitats. The PlanHab study investigated microgravity through inactivity in bed rest and normobaric hypoxia to examine their independent or combined effect on adenosine and its kinetics. Healthy male subjects (n = 14) completed three 21-day interventions: hypoxic bed rest (HBR); hypoxic ambulatory confinement (HAMB); normoxic bed rest (NBR). The interventions were separated by 4 months. Our hypothesis of a hypoxia-triggered increase in adenosine was confirmed in HAMB but unexpectedly also in NBR. However, the highest adenosine levels were noted following HBR. Furthermore, the percentage of hemolysis was elevated in HBR whereas endothelial integrity markers stayed low in all three interventions. In summary, these data suggest that neocytolysis accounts for these effects while we could reduce evidence for microcirculatory changes.
Assuntos
Adenosina/metabolismo , Hipóxia/metabolismo , Adulto , Repouso em Cama/métodos , Humanos , Cinética , Masculino , Microcirculação/fisiologia , Ausência de PesoRESUMO
BACKGROUND: Lamellar keratoplasties, e.g. Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) are considered the procedures of choice for corneal endothelial diseases. In comparison to penetrating keratoplasty (PK) they are associated with faster visual rehabilitation, a lower risk of complications and a decreased necessity for follow-up visits, which reduces the burden on quality of life in elderly patients. In order to advise patients regarding the indications for surgery and to facilitate the follow-up management, it is important to know the most important complications associated with these keratoplasty techniques. RESULTS AND DISCUSSION: The most important preoperative complication is a delayed indication for the operation. In contrast to PK, DSAEK and DMEK surgery should be provided at an earlier stage of disease as chronic edema alters the stroma and reduces the speed of visual recovery. The most important complications during or early after surgery are detached lamellae, pupillary blocks with increased pressure or air bubbles in the vitreous cavity in patients with previous vitrectomy. The main long-term complications include chronic increased intraocular pressure and immune-mediated graft rejections in DSAEK patients after reducing or stopping topical corticosteroid therapy. This article describes the potential complications of endothelial keratoplasty and provides a detailed explanation of strategies to avoid these complications.
Assuntos
Doenças da Córnea/etiologia , Doenças da Córnea/terapia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos , Traumatismos Oculares/terapia , Rejeição de Enxerto/etiologia , Hipertensão Ocular/etiologia , Doenças da Córnea/diagnóstico , Medicina Baseada em Evidências , Traumatismos Oculares/diagnóstico , Traumatismos Oculares/etiologia , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/prevenção & controle , Humanos , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/prevenção & controle , Resultado do Tratamento , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia , Transtornos da Visão/prevenção & controleRESUMO
BACKGROUND: To develop an algorithm based on the ocular pulse amplitude (OPA) to predict the probability of a positive temporal artery biopsy (TAB) result in the acute phase of suspected giant cell arteritis (GCA). METHODS: Unilateral TAB was performed and ipsilateral OPA measurements were taken by Dynamic Contour Tonometry. Among the clinical signs and laboratory findings tested in univariate analyses, OPA, Erythrocyte Sedimentation Rate (ESR) and thrombocyte count showed a strong association with a positive TAB result. Algorithm parameters were categorized into three groups (OPA >3.5, 2.5-3.5, and <2.5 mm Hg; ESR <25, 25-60, and >60 mm/h; thrombocyte count <250'000, 250'000-500'000, and >500'000/µl). Score values (0, 1, and 2) were attributed to each group, resulting in a total score range from 0 to 6. A univariate logistic regression analysis using the GCA diagnosis as the dependent and the total score as the independent variate was fitted and probability estimates were calculated. RESULTS: Thirty-one patients with suspected GCA undergoing TAB during an eighteen-month observation period were enrolled. Twenty patients showed histologically proven GCA. Four patients had score values ≤2, fourteen between 3 and 4, and thirteen of ≥5. The corresponding estimated probabilities of GCA were<7, 52.6, and >95%. CONCLUSION: The present study confirms previous findings of reduced OPA levels, elevated ESR, and elevated thrombocyte counts in GCA. It indicates that a sum score based on OPA, ESR, and thrombocyte count can be helpful in predicting TAB results, especially at the upper and the lower end of the sum score range.
Assuntos
Algoritmos , Pressão Sanguínea/fisiologia , Arterite de Células Gigantes/diagnóstico , Pressão Intraocular/fisiologia , Artérias Temporais/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Contagem de Plaquetas , Estudos ProspectivosRESUMO
PURPOSE: Anti-VEGF treatment has a potent vasoconstrictive effect. Early changes of retinal blood flow velocity (RBFV) measured using the Retinal Function Imager (RFI) combined with indicators of vascular status may help in predicting the visual outcome 1 month post injection in patients with neovascular age-related macular degeneration (nvAMD) under ranibizumab treatment. To develop a simple prediction model based on the change in RBFV 3 days post injection and indicators of a patient's vascular status to assess the probability of a successful visual outcome 1 month post injection. METHODS: RBFV measured using RFI were prospectively collected pre-injection and 3 days post injection in 18 eyes of 15 patients. Indicators of vascular status (history of hypertension, diabetes mellitus without retinal affection, and smoking) were assessed by medical history. By univariate analyses, parameters associated with visual outcome were weighted (-1 to 6 points). A multivariate logistic regression model with the categorized visual outcome parameter (≥0 letters gained after 1 month) as the dependent variate and the sum score as the independent variate (continuous scale) was used to estimate the score value-specific probabilities of letters gained ≥0 1 month post injection. RESULTS: The indicators of vascular status negatively influenced the likelihood of a letter gain ≥0 whereas an increase in the arterial RBFV strongly increased it. The area under the receiver operating characteristics curve for these parameters investigated was 0.71 (95% CI: 0.43-1.00). CONCLUSION: Changes in the arterial RBFV following 3 days after ranibizumab injection combined with three indicators of the vascular status identified nvAMD patients with favorable visual outcome accurately.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Ranibizumab/uso terapêutico , Artéria Retiniana/fisiologia , Estroboscopia/instrumentação , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/fisiopatologia , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo/fisiologia , Técnicas de Diagnóstico Oftalmológico , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Modelos Estatísticos , Estudos Prospectivos , Fluxo Sanguíneo Regional/fisiologia , Estroboscopia/métodos , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologiaRESUMO
PURPOSE: The aim of this study was to assess whether intraoperative testing of silicone Ahmed glaucoma valves (AGVs) would identify valves with an increased risk of low postoperative intraocular pressure (IOP). METHODS: In 30 consecutive cases of glaucoma surgery with AGV implantation, after priming the AGV, we intraoperatively measured the opening pressure A, closing pressure B, and re-opening pressure C using the active infusion pump of a phako-machine. IOP was checked postoperatively on the same day. Low IOP was defined as <5 mm Hg. Intraoperatively measured pressure characteristics of the valve function were analysed for their ability to predict postoperative IOP outcomes. RESULTS: Opening A, closing B, and re-opening C pressures (mean, (SD)) were 18.4 (5.1), 8.3 (4.7), and 11.7 (4.8)mm Hg, respectively. Ten patients (33.3%) had low IOP. An opening pressure of ≤18 mm Hg predicted low postoperative IOP with a sensitivity (10/10) of 100% (95% CI, 69.2-100) and a specificity (13/20) of 65.0% (95% CI, 40.8-84.6). CONCLUSIONS: AGVs have a high variability of opening, closing, and re-opening pressures. An opening pressure of ≤18 mm Hg, a closing pressure of ≤10 mm Hg, or a re-opening pressure of ≤11 mm Hg identified all patients with low postoperative IOP.
Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma/cirurgia , Pressão Intraocular , Teste de Materiais , Hipotensão Ocular/diagnóstico , Implantação de Prótese , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Período Intraoperatório , Pessoa de Meia-Idade , Hipotensão Ocular/prevenção & controle , Pressão , Curva ROC , Tonometria OcularRESUMO
PURPOSE: To compare the effect, failure rate and the risks of corneal cross-linking (CXL) in keratoconus patients aged ≥35 years to patients <35 years. METHODS: In 141 eyes of 116 keratoconus patients we compared the changes in best phoropter-corrected visual acuity (BCVA) and maximum keratometry values (Kmax) before and 12 months after CLX in patients aged ≥35 years (n=34, 38 eyes) to the cohort of patients below 35 years of age. RESULTS: Overall, CXL significantly improved BCVA from 0.487 logMAR (95% confidence interval (CI) 0.426-0.548) by -0.197 logMAR (95% CI -0.243 to -0.150; P<0.001) and reduced Kmax from 48.96 diopter (Dpt) by -1.33 Dpt (95% CI -1.85 to -0.81: P<0.001). Age ≥35 years had no effect on the changes of BCVA (-0.02 (95% CI -0.13 to 0.09); P=0.757) or Kmax (0.58 (95%CI -0.51 to 1.68); P=0.294) as compared with younger patients. In 54 patients (55 eyes, 38.5%) aged <35 years and in 18 patients (18 eyes, 47.4%) aged ≥35 years, BCVA increased by ≥2 Snellen lines. Failure (increase in Kmax ≥1 Dpt) was observed in 17 eyes (16.5%) of patients aged <35 years and in 3 eyes (7.9%) of patients aged ≥35 years during the 12-month follow-up period. Adverse outcomes (loss of ≥2 Snellen lines) occurred in 4 (3.9%) eyes of patients aged <35 years and 1 (2.6%) eye of a patient aged ≥35 years. CONCLUSION: Effects and adverse events of CXL treatment do not seem to differ between subjects younger or older than 35 years.
Assuntos
Reagentes de Ligações Cruzadas/uso terapêutico , Ceratocone/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Complicações Pós-Operatórias , Riboflavina/uso terapêutico , Acuidade Visual/fisiologia , Adulto , Fatores Etários , Córnea/fisiopatologia , Topografia da Córnea , Reagentes de Ligações Cruzadas/efeitos adversos , Feminino , Seguimentos , Humanos , Ceratocone/fisiopatologia , Masculino , Fármacos Fotossensibilizantes/efeitos adversos , Estudos Retrospectivos , Riboflavina/efeitos adversos , Falha de Tratamento , Raios Ultravioleta , Adulto JovemRESUMO
BACKGROUND: The recent introduction of amendments to the medical licensure laws led to the introduction of the field of pain medicine into the study program "Human Medicine". The implementation has to be completed by all medical faculties before 2016. MATERIAL AND METHODS: Pain medicine was implemented into the model study course"MaReCuM" at the medical faculty in Manheim as a compulsory subject in the year 2010. It is structured into five sections in a longitudinal manner. The core section is the "pain awareness week" in the fifth academic year of the medical studies. The content and structure is based on the German Pain Society (DGSS) curriculum. For the purpose of this study the examination results and the student evaluation forms from the academic years 2010/2011 and 2011/2012 were analyzed. RESULTS: The students regarded pain medicine as being highly relevant concerning its impact on the professional activities. The competence to develop a specific and individual therapy was of special interest. A good coordination of the contents of teaching between preclinical and clinical teaching was considered to be of major importance. CONCLUSIONS: The DGSS curriculum is a useful tool for the implementation of pain medicine in a study program. In order to improve access to basic pain medicine in general, a combined teaching program consisting of pain medicine and general medicine could be helpful. Pain medicine could be used as a guide for teaching contents of outpatient medicine.
Assuntos
Currículo/normas , Educação Médica/normas , Medicina , Modelos Educacionais , Manejo da Dor/normas , Sociedades Médicas , Atitude do Pessoal de Saúde , Docentes de Medicina , Alemanha , Humanos , Licenciamento em Medicina/normas , Estudos Longitudinais , Cuidados Paliativos , Estudantes de Medicina/psicologiaRESUMO
The human immune system is orchestrated in a complex manner and protects the host against invading organisms and controls adequate immune responses to different antigen challenges in an endo-, auto- and paracrine-regulated fashion. The variety and intensity of immune responses are known to be dependent on stress-sensitive neural, humoral and metabolic pathways. The delayed-type hypersensitivity (DTH) skin test was a validated and standardized measure applied in clinical studies to monitor the integral function of cellular immune responses in vivo. The DTH skin test was, however, phased out in 2002. To obtain insight into the mechanisms of stress-sensitive immune reactions, we have developed an alternative in-vitro assay which allows the evaluation of antigen-dependent cellular immune responses triggered by T lymphocytes. The change in the concentration of proinflammatory cytokines in supernatant of the blood-antigen mixture is of particular interest to mirror the degree and adequacy of cellular immune responses. In this study we report that the proinflammatory cytokines interleukin (IL)-2, interferon (IFN)-γ and tumour necrosis factor (TNF)-α show a time-dependent increase upon ex-vivo bacterial, viral and fungal antigen stimulations. Furthermore, evidence is provided that this assay is sensitive to mirror stress hormone-mediated immune modulation in humans as shown either after hydrocortisone injection or after acute stress exposure during free fall in parabolic flight. This in-vitro test appears to be a suitable assay to sensitively mirror stress hormone-dependent inhibition of cellular immune responses in the human. Because of its standardization and relatively simple technical handling, it may also serve as an appropriate research tool in the field of psychoneuroendocrinology in clinical as in field studies.
Assuntos
Bioensaio/métodos , Monitorização Imunológica/métodos , Estresse Fisiológico/imunologia , Corticosteroides , Adulto , Bactérias/imunologia , Fungos/imunologia , Humanos , Hidrocortisona/análise , Imunidade Celular , Interferon gama/análise , Interleucina-2/análise , Masculino , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/análise , Vírus/imunologiaRESUMO
The cancer-testis antigen NY-ESO-1 is a potential target antigen for immune therapy expressed in a subset of patients with multiple myeloma. We generated chimeric antigen receptors (CARs) recognizing the immunodominant NY-ESO-1 peptide 157-165 in the context of HLA-A*02:01 to re-direct autologous CD8(+) T cells towards NY-ESO-1(+) myeloma cells. These re-directed T cells specifically lysed NY-ESO-1(157-165)/HLA-A*02:01-positive cells and secreted IFNγ. A total of 40% of CCR7(-) re-directed T cells had an effector memory phenotype and 5% a central memory phenotype. Based on CCR7 cell sorting, effector and memory CAR-positive T cells were separated and CCR7(+) memory cells demonstrated after antigen-specific re-stimulation downregulation of CCR7 as sign of differentiation towards effector cells accompanied by an increased secretion of memory signature cytokines such as IL-2. To evaluate NY-ESO-1 as potential target antigen, we screened 78 bone marrow biopsies of multiple myeloma patients where NY-ESO-1 protein was found to be expressed by immunohistochemistry in 9.7% of samples. Adoptively transferred NY-ESO-1-specific re-directed T cells protected mice against challenge with endogenously NY-ESO-1-positive myeloma cells in a xenograft model. In conclusion, re-directed effector- and central memory T cells specifically recognized NY-ESO-1(157-165)/ HLA-A*02:01-positive cells resulting in antigen-specific functionality in vitro and in vivo.
Assuntos
Antígenos de Neoplasias/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunoterapia , Mieloma Múltiplo/terapia , Proteínas de Neoplasias/imunologia , Fragmentos de Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Animais , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/transplante , Linhagem Celular Tumoral , Terapia Genética , Humanos , Memória Imunológica , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-2/genética , Interleucina-2/metabolismo , Camundongos , Mieloma Múltiplo/imunologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores CCR7/genética , Receptores CCR7/metabolismo , Transdução GenéticaRESUMO
The FAM20 family of secreted proteins consists of three members (FAM20A, FAM20B, and FAM20C) recently linked to developmental disorders suggesting roles for FAM20 proteins in modulating biomineralization processes. The authors report here findings in knockout mice having null mutations affecting each of the three FAM20 proteins. Both Fam20a and Fam20c null mice survived to adulthood and showed biomineralization defects. Fam20b (-/-) embryos showed severe stunting and increased mortality at E13.5, although early lethality precluded detailed investigations. Physiologic calcification or biomineralization of extracellular matrices is a normal process in the development and functioning of various tissues (eg, bones and teeth). The lesions that developed in teeth, bones, or blood vessels after functional deletion of either Fam20a or Fam20c support a significant role for their encoded proteins in modulating biomineralization processes. Severe amelogenesis imperfecta (AI) was present in both Fam20a and Fam20c null mice. In addition, Fam20a (-/-) mice developed disseminated calcifications of muscular arteries and intrapulmonary calcifications, similar to those of fetuin-A deficient mice, although they were normocalcemic and normophosphatemic, with normal dentin and bone. Fam20a gene expression was detected in ameloblasts, odontoblasts, and the parathyroid gland, with local and systemic effects suggesting both local and/or systemic effects for FAM20A. In contrast, Fam20c (-/-) mice lacked ectopic calcifications but were severely hypophosphatemic and developed notable lesions in both dentin and bone to accompany the AI. The bone and dentin lesions, plus the marked hypophosphatemia and elevated serum alkaline phosphatase and FGF23 levels, are indicative of autosomal recessive hypophosphatemic rickets/osteomalacia in Fam20c (-/-) mice.
Assuntos
Amelogênese Imperfeita/veterinária , Proteínas de Ligação ao Cálcio/genética , Proteínas da Matriz Extracelular/genética , Osteomalacia/veterinária , Proteínas/genética , Raquitismo/veterinária , Fosfatase Alcalina/sangue , Amelogênese Imperfeita/metabolismo , Amelogênese Imperfeita/patologia , Animais , Cálcio/sangue , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas do Esmalte Dentário/genética , Proteínas do Esmalte Dentário/metabolismo , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/metabolismo , Feminino , Fator de Crescimento de Fibroblastos 23 , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteomalacia/metabolismo , Osteomalacia/patologia , Fenótipo , Fósforo/sangue , Proteínas/metabolismo , Radiografia , Raquitismo/metabolismo , Raquitismo/patologia , Dente/diagnóstico por imagem , Dente/metabolismo , Dente/patologia , Calcificação de DenteRESUMO
BACKGROUND: In current literature the prognosis of trisomy 18 is mainly described as inevitably lethal. After intervention of parental organisations infants have been treated with cardio surgery in the USA, later in Europe as well with good results. We report the consequences of this and similar developments on our pre- und postnatal approach after diagnosis in our department. PATIENTS AND CASE REPORTS: 2 parents decided to carry the child to term after the recommendation for abortion. According to standard perinatological aspects one child was vaginally delivered, the second with Caesarean section. After informed consent with the parents we planned a supportive management without more resuscitation than stimulation and ventilation by mask. Both children could be stabilised with nasal CPAP. The first one had been operated on a double outlet right ventricle at the age of 6 months, the second needed to be operated for diaphragm hernia. The third child had been delivered by emergency Caesarean section. A bilateral choanal atresia had been operated in the first week of life, a double outlet right ventricle at the age of 15 days. One child is fed by a nasogastric tube, one is bottle-fed and one had a percutanous gastric tube until he died due to septicaemia, all have statomotorically retardation and had periods of pulmonary hypertension. The social situation of the families is characterised by a stable parental relationship and a safe socio-economical status. None of the children had an acute lethal malformation. DISCUSSION: In single cases a prospective management in patients with trisomy 18 can be possible. Besides medical issues, the emotional parental wish, their social network and economical status are crucial. CONCLUSION: The prognosis of trisomy 18 is poor. 3 patients and 20 months do not allow any general statements. However, our recent experience and the courses in the recent literature show that in single cases a more prospective management is possible.
Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/terapia , Trissomia/diagnóstico , Trissomia/genética , Anormalidades Múltiplas/genética , Cromossomos Humanos Par 18/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome , Resultado do TratamentoRESUMO
Age-related cataracts are mainly caused by life-long accumulation of oxidative stress on the lens fibres. Symptoms include reduced visual acuity, requiring more light for reading, and glare. The only treatment that provides a cure for cataracts is surgery. Phacoemulsification represents the preferred method of lens removal. It involves fragmentation of the lens using ultrasound and insertion of an artificial intraocular lens. The preoperative assessment the general practitioner provides to surgeon and anesthesia team has an important share in the low complication rate of the procedure in the event of co-existing systemic disease. Growing patient expectation for spectacle independence following cataract surgery is met to some extent using techniques for astigmatism control and presbyo-pia-correcting intraocular lenses.
Assuntos
Catarata , Lentes Intraoculares , Facoemulsificação , Adulto , Fatores Etários , Idoso , Astigmatismo/cirurgia , Catarata/diagnóstico , Catarata/diagnóstico por imagem , Medicina de Família e Comunidade , Humanos , Estresse Oxidativo , Presbiopia/cirurgia , Fatores de Risco , UltrassonografiaAssuntos
Doenças da Córnea/complicações , Doenças da Córnea/diagnóstico , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/diagnóstico , Doenças da Córnea/terapia , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/etiologia , Síndromes do Olho Seco/terapia , Feminino , Humanos , Hipercalcemia/terapia , Pessoa de Meia-Idade , Neoplasias das Paratireoides/terapiaRESUMO
BACKGROUND: Previously performed in vitro studies suggested that gravitational stress may alter functions of immune cells. This study investigated the in vivo effects of parabolic flight manoeuvres as a short-term model of micro- and hypergravity on the cytotoxic and microbicidal polymorphonuclear leucocyte (PMN) functions as the key element of innate immunity. MATERIAL AND METHODS: Twenty-one healthy male volunteers underwent 30 subsequent parabolic flight manoeuvres. Each manoeuvre produced 22-s periods of nearly weightlessness close to <<0g>>, with each parabola starting with a pull-up and ending with a pull-out (hypergravity) at 1.8 g for about 20 s each. Blood samples were drawn 24 h prior to take off (T0), after 25-30 parabolas (T1), and 24 h (T2) and 48 h (T3) after flight for determination of (i) leucocyte number and subpopulations, (ii) PMNs' capabilities to produce hydrogen peroxide (H(2)O(2)) and to adhere and phagocytose particles and (iii) plasma cytokines known to prime PMN functions [interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-alpha), granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF)]. RESULTS: Parabolic flight induced an increase in leucocyte number with a significant elevation of the PMN fraction. The spontaneous H(2)O(2) production by PMNs did not change; however, the capability of PMNs to produce H(2)O(2) in response to soluble stimuli [N-formyl-methionyl-leucyl-phenylalanine (fMLP), fMLP and TNF-alpha, calcium ionophore (A23187), phorbol myristate acetate (PMA)] was increased. Adhesive and phagocytic properties of PMNs were not altered. Regarding priming cytokines, IL-8 and G-CSF were significantly elevated. CONCLUSIONS: Our data indicate that parabolic flight induces priming of the cytotoxic capabilities of PMNs without affecting microbicidal functions.
Assuntos
Peróxido de Hidrogênio/farmacologia , Neutrófilos/fisiologia , Fagocitose/fisiologia , Câmaras de Exposição Atmosférica , Gravidade Alterada/efeitos adversos , Humanos , Masculino , Neutrófilos/imunologia , Fagocitose/imunologiaRESUMO
The progress in antibody engineering over the last 20 years has created the tools for the development of novel antibody-based drugs and constructs, such as small antibody fragments, suitable for topical administration. In rheumatology, oncology, transplantation medicine and ophthalmology, therapeutic antibody constructs, and antibody fragments have been responsible for the clinical progress seen over the last decade. Although antibody-based therapies have become a well-established immunosuppressive option in solid organ transplantation, there are only very few reports with regard to corneal transplantation. The following review explains some of the important aspects of engineered antibody-based therapeutic agents and summarises the current use of such immunosuppressive therapies in transplantation medicine and corneal transplantation.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Transplante de Córnea/métodos , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , HumanosRESUMO
The risk of paraplegia and paraparesis during thoracoabdominal aneurysm surgery still represents a major threat. In 1993, Cambria and coworkers applied for the first time a method of regional spinal cord hypothermia by epidural cooling and significantly diminished the rate of neurological deficits. In this article the first clinical application of this neuroprotective method in Germany will be reported. This neuroprotective method was used in seven patients who underwent elective thoracoabdominal aortic aneurysm repair. The spinal cord was cooled with ice-cold saline via an epidural catheter during surgical repair. Cerebrospinal fluid pressure was measured on-line via a spinal catheter and controlled using active cerebrospinal fluid drainage. Of these seven patients, four showed no postoperative neurological deficit and were released from hospital. The other three patients died in the intra-operative or post-operative phase due to complications other than spinal cord injury arising from pre-existing comorbid conditions. The described method of epidural cooling represents a preliminary experimental method, which might reduce spinal cord injury during surgical repair of thoracoabdominal aneurysms.
Assuntos
Aneurisma da Aorta Torácica/terapia , Espaço Epidural/fisiologia , Hipotermia Induzida , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/prevenção & controle , Adulto , Idoso , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/cirurgia , Temperatura Corporal , Líquido Cefalorraquidiano/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Isquemia do Cordão Espinal/prevenção & controle , Resultado do TratamentoRESUMO
BACKGROUND: Topical preparations, high in phosphate, may cause calcification when used on a damaged corneal surface. The knowledge of the phosphate concentration in medications helps to prevent corneal calcifications. Our study gives an overview of the amount of phosphate contained in ophthalmic corticoid preparations. METHODS: Samples of 38 commercially available corticoid preparations were tested. The quantification of phosphate was performed using the molybdate method on a Modular P autoanalyzer. RESULTS: 18 of 38 preparations (47%) had a phosphate concentration above physiological levels (>1.45 mmol/l). It varied greatly, and ranged from less than 0.1 mmol/l (18 preparations) to 62.6 mmol/l. The corticoids that were tested included betamethasone sodium phosphate (18.3-35.5 mmol/l), dexamethasone (0.1-17.6 mmol/l), dexamethasone sodium phosphate (<0.1-62.6 mmol/l), fluorometholone (<0.1-22.5 mmol/l), and prednisolone acetate (<0.1-0.5 mmol/l). CONCLUSIONS: The phosphate concentration in corticoid-phosphate formulations varies greatly, and is mainly determined by the chosen buffer. The prednisolone acetate preparations showed physiological phosphate concentrations. For a treatment on a damaged corneal surface, preparations with physiological phosphate concentrations should be used.
Assuntos
Glucocorticoides/química , Soluções Oftálmicas/química , Fosfatos/análise , Autoanálise , Calcinose/metabolismo , Calcinose/prevenção & controle , Doenças da Córnea/metabolismo , Doenças da Córnea/prevenção & controleRESUMO
The prevalence of urinary incontinence is around 20% of healthy middle-aged women. Incontinence causes a negative impact on the quality of life and sexuality. From August 2002 to January 2004, 30 patients (mean age 43 years) with stress urinary incontinence (59%), overactive bladder (15%) and mixed incontinence (26%) answered the ICIQ-SF(International Consultation on Incontinence Questionnarie-Short Form) and FSFI (Female Sexual Function Index) questionnaires before and after treatment for urinary incontinence. The follow-up ranged from 12 to 53 months. Mean ICIQ score was 17 and 7 before and after treatment respectivelly (p<0,001). Overactive bladder showed the worst scores in all domains. The patients who underwent surgery increased their scores of desire (p=0,02), satisfaction (p=0,05) and total score (p=0,02). Thirteen patients which ICIQ was zero increased: desire (p<0,01), satisfaction (p=0,05) and total score (p=0,01). Urinary incontinence significantly affects the quality of life. Therefore sexual evaluation in incontinence patients is recommended.
Assuntos
Sexualidade , Incontinência Urinária/terapia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Adenoviral conjunctivitis causes high socioeconomic costs due to high contagiousness and therefore the need for extended quarantine. To date the only potentially active, topical antiviral agent is povidone-iodine (PVI). The aim of this study was to investigate the effect of diluted PVI on free adenovirus and adenoviral infected cells as well as to evaluate the cellular toxicity of PVI on non-infected cells. MATERIAL AND METHODS: PVI was diluted to a final concentration of 0.0008 %. Virucidal activity was measured IN VITRO using adenovirus 8 and A549 human epithelial cell cultures. Cytotoxicity effects on healthy cells after short- and long-term exposure to diluted PVI were measured in A549 cell cultures. RESULTS: Exposure to PVI at a concentration of 1:10 (0.8 %) completely extinguishes infectivity of free adenovirus after an exposure time of 10 minutes. PVI is less effective against intracellular adenovirus resulting in a decreased infectivity and viral activity for approximately one day with a narrow spectrum between toxicity and virucidal activity. Healthy epithelial cells can be exposed to PVI for up to 6 hours without a cytotoxic effect. CONCLUSIONS: PVI is highly effective against free adenovirus but less effective against intracellular adenoviral particles in already infected cell. Short- and long-term exposure of PVI causes little cytotoxicity for healthy cells. Therefore, administration of diluted PVI at a concentration of 1:10 is a potential option to reduce contagiousness in cases of adenoviral infections.