Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
1.
Ophthalmologie ; 121(4): 291-297, 2024 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-38252294

RESUMEN

BACKGROUND: Endogenous Candida endophthalmitis is an emergency that can threaten vision and the eye as a whole organ but also the life of the patient due to its systemic cause. MATERIAL AND METHOD: Retrospective case evaluation of the University Hospital for Ophthalmology Halle (Saale) and the Eye Clinic of the Ernst von Bergmann Hospital Potsdam from 2017-2022. (Age, gender, side involvement, underlying diseases, symptoms, preoperative and postoperative visual acuity, diagnostics, treatment and complications). The standardized procedures for endogenous Candida endophthalmitis are explained, the data are compared with the literature and treatment suggestions are presented. RESULTS: 8 patients with 14 eyes were treated for endogenous Candida endophthalmitis. Of the patients 2 were women and 6 were men. The overall average age was 70.25 years (53-82 years), 6 patients had bilateral eye involvement and 2 patients were affected on one side. All patients had several serious immunocompromising underlying diseases that were the cause of the candidemia. All patients underwent a pars plana vitrectomy (ppV) on the affected eyes except for one male patient who did not obtain permission for anesthesia. In addition to systemic treatment with antimycotics, voriconazole was routinely administered intravitreally during ppV. The patients received further intravitreal doses of voriconazole based on the findings. Vitreous body samples were taken from all patients during the ppV and detection of Candida albicans was possible in all cases. As part of the local perioperative treatment 1 patient received parabulbar administration of a triamcinolone depot in both eyes, 7 patients received a dexamethasone depot in 11 eyes and all 8 patients received findings-oriented local treatment with prednisolone acetate eye drops. visual acuity increased from preoperatively 1.2 logMar to 1.0 logMar. Postoperative retinal detachment did not occur and there were no serious perioperative complications. 2 patients died from one of the underlying diseases after 3 and 25 months, respectively. CONCLUSION: Despite an increasing number of case series, there are still no uniform guidelines for ophthalmologists in Germany. There is agreement regarding systemic treatment and the intravitreal administration of antifungal agents. The role of ppV has not yet been clearly defined and the question of the adjuvant use of steroids (systemic and/or local) has also not been conclusively clarified.


Asunto(s)
Endoftalmitis , Humanos , Masculino , Femenino , Anciano , Endoftalmitis/diagnóstico , Voriconazol/uso terapéutico , Estudios Retrospectivos , Cuerpo Vítreo/microbiología , Candida albicans
2.
Ophthalmologie ; 121(4): 272-281, 2024 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-38252295

RESUMEN

Endogenous Candida endophthalmitis is a rare but vision-threatening disease. In most cases, endogenous endophthalmitis caused by Candida species has a better prognosis than endogenous endophthalmitis caused by other fungal species or bacteria but the prognosis still depends heavily on the time required for diagnosis and subsequent treatment as well as the initial visual acuity. Suggestions for treatment algorithms have already been made in the past but binding guidelines in ophthalmology only exist sporadically due to the rarity of the disease. This review discusses the current knowledge on endogenous Candida endophthalmitis and draws conclusions from the current study situation.


Asunto(s)
Endoftalmitis , Vitrectomía , Humanos , Endoftalmitis/diagnóstico , Pronóstico , Bacterias , Candida
3.
Ophthalmologe ; 117(5): 461-466, 2020 May.
Artículo en Alemán | MEDLINE | ID: mdl-31388758

RESUMEN

Minimally invasive glaucoma surgery (MIGS) implants, such as XEN® gel stent are additional procedures in glaucoma treatment, which were designed to reduce the postoperative risk of severe hypotony and further complications. Until now the contraindications for every implant have not yet been identified. This case report describes the disastrous follow-up after implantation of a XEN® gel stent in the only high myopic eye of a patient. Despite elaborate subsequent interventions massive choroidal hemorrhage occurred with loss of the remaining visual field and total loss of visual acuity. The ocular pressure could be stabilized only after explantation of the XEN® gel stent. Patients with high myopia and the associated thin sclera, vitrectomized eyes and previous treatment with mitomycin C should be selected very carefully for XEN® gel stent. If these criteria are present the XEN® gel stent should be avoided whenever possible.


Asunto(s)
Glaucoma , Miopía , Contraindicaciones , Glaucoma/cirugía , Implantes de Drenaje de Glaucoma , Humanos , Presión Intraocular , Stents , Vitrectomía
4.
Ophthalmologe ; 116(12): 1171-1176, 2019 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-31338590

RESUMEN

PURPOSE: Every year around New Year's Eve severe eye injuries are caused by fireworks. There is a large variety ranging from slight superficial injuries to very severe trauma necessitating extensive and sometimes repeated surgical treatment. As a consequence the patients not only suffer from functional or cosmetic impairments but also from socioeconomic problems, such as reduced capacity to work and inability to work. All firework-related eye injuries treated at the University Hospital Halle from 2008 to 2018 were retrospectively and systematically analyzed. MATERIAL AND METHODS: The patients were analyzed with respect to age, gender, injury distribution, type of injury, circumstances, form of treatment, consequences and duration of inability to work. RESULTS: From the turn of the year 2008/2009 to the turn of the year 2018/2019 a total of 144 eyes from 116 patients were treated at the ophthalmology department of the University Hospital Halle. The injuries involved 80 male patients (69%) and 36 female patients (31%), among them 44 children (38%) aged under 18 years, 81 right and 63 left eyes. In 28 patients both eyes were affected. Of the patients 44% handled the fireworks themselves and 56% were bystanders. Injuries were mostly caused by bangers (37%) and rockets (24%). Of the patients 37 had to be hospitalized, 14 eyes needed immediate surgical treatment, 2 eyes needed surgery later on in irritation-free intervals and 12 eyes needed repeated surgery. The duration of inability to work was on average 21.6 days, 2 eyes went blind because of the fireworks-related injury and 29% of the patients had visual impairments of which 43% were classified as severe impairments. CONCLUSION: Fireworks-related injuries are preventable injuries. As in most cases children, young adults and bystanders are affected by fireworks injuries, prophylactic and educational programs are urgently needed and legal regulations are necessary.


Asunto(s)
Traumatismos por Explosión , Lesiones Oculares , Adolescente , Traumatismos por Explosión/epidemiología , Traumatismos por Explosión/terapia , Niño , Lesiones Oculares/epidemiología , Lesiones Oculares/terapia , Femenino , Hospitales Universitarios , Humanos , Masculino , Oftalmología/estadística & datos numéricos , Estudios Retrospectivos , Adulto Joven
5.
Ophthalmologe ; 116(12): 1212-1215, 2019 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-30923896

RESUMEN

Trauma surgeons are often confronted with severe complex eyeball injuries. The primary wound treatment and internal reconstruction are carried out depending on the surgical experience. The following case report describes a patient with severe eyeball rupture, from the preoperative findings up to the current status 1 year after the injury. After the initial severe trauma and complex primary reconstruction with subsequent pole to pole surgery in the irritation-free interval, a good functional and cosmetic result was achieved. Even after severe eyeball injuries the best possible primary reconstruction should be strived for. Secondary corrections are possible in irritation-free periods and can help the patient to achieve functional and cosmetic rehabilitation.


Asunto(s)
Lesiones Oculares , Procedimientos de Cirugía Plástica , Lesiones Oculares/cirugía , Humanos , Rotura
6.
Anaesthesist ; 67(12): 922-930, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30338337

RESUMEN

BACKGROUND: Dural puncture, paraesthesia and vascular puncture are the most common complications of epidural catheter insertion. Their association with variation in midline needle insertion depth is unknown. OBJECTIVE: This study evaluated the risk of dural and vascular punctures and the unwanted events paraesthesia and multiple skin punctures related to midline needle insertion depth. MATERIAL AND METHODS: A total of 14,503 epidural catheter insertions including lumbar (L1-L5; n = 5367), low thoracic (T7-T12, n = 8234) and upper thoracic (T1-T6, n = 902) insertions, were extracted from the German Network for Regional Anaesthesia registry between 2007 and 2015. The primary outcomes were compared with logistic regression and adjusted (adj) for confounders to determine the risk of complications/events. Results are presented as odds ratios (OR, [95% confidence interval]). MAIN RESULTS: Midline insertion depth depended on body mass index, sex, and spinal level. After adjusting for confounders increased puncture depth (cm) remained an independent risk factor for vascular puncture (adjOR 1.27 [1.09-1.47], p = 0.002) and multiple skin punctures (adjOR 1.25 [1.21-1.29], p < 0.001). In contrast, dural punctures occurred at significantly shallower depths (adjOR 0.73 [0.60-0.89], p = 0.002). Paraesthesia was unrelated to insertion depth. Body mass index and sex had no influence on paraesthesia, dural and vascular punctures. Thoracic epidural insertion was associated with a lower risk of vascular puncture than at lumbar sites (adjOR 0.39 [0.18-0.84], p = 0.02). CONCLUSION: Variation in midline insertion depth is an independent risk factor for epidural complications; however, variability precludes use of depth as a reliable guide to insertion in individual patients.


Asunto(s)
Anestesia Epidural/efectos adversos , Adulto , Anciano , Anestesia Epidural/instrumentación , Anestesia Epidural/estadística & datos numéricos , Anestesia Obstétrica , Cateterismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agujas , Punciones/estadística & datos numéricos , Factores de Riesgo
7.
Science ; 353(6304)2016 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-27609898

RESUMEN

New biological models are incorporating the realistic processes underlying biological responses to climate change and other human-caused disturbances. However, these more realistic models require detailed information, which is lacking for most species on Earth. Current monitoring efforts mainly document changes in biodiversity, rather than collecting the mechanistic data needed to predict future changes. We describe and prioritize the biological information needed to inform more realistic projections of species' responses to climate change. We also highlight how trait-based approaches and adaptive modeling can leverage sparse data to make broader predictions. We outline a global effort to collect the data necessary to better understand, anticipate, and reduce the damaging effects of climate change on biodiversity.


Asunto(s)
Adaptación Fisiológica , Biodiversidad , Evolución Biológica , Cambio Climático , Modelos Biológicos , Animales , Conservación de los Recursos Naturales , Culicidae/virología , Dengue/transmisión , Planeta Tierra , Modelos Genéticos , Dinámica Poblacional , Análisis Espacio-Temporal
8.
Ann Oncol ; 27(10): 1916-22, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27456299

RESUMEN

BACKGROUND: Central venous catheter (CVC)-related bloodstream infections (CRBSI) are a frequent cause of morbidity and mortality in patients with chemotherapy-induced neutropenia. Chlorhexidine containing catheter securement dressings may prevent CRBSI. PATIENTS AND METHODS: A multicenter randomized, controlled trial was conducted at 10 German hematology departments. We compared chlorhexidine-containing dressings with non-chlorhexidine control dressings in neutropenic patients. The primary end point was the incidence of definite CRBSI within the first 14 days (dCRBSI14) of CVC placement. Secondary end points included combined incidence of definite or probable CRBSI within 14 days (dpCRBSI14), overall (dpCRBSI), incidence of unscheduled dressing changes and adverse events. RESULTS: From February 2012 to September 2014, 613 assessable patients were included in the study. The incidence of dCRBSI14 was 2.6% (8/307) in the chlorhexidine and 3.9% (12/306) in the control group (P = 0.375). Both dpCRBSI14 and dpCRBSI were significantly less frequent in the study group with dpCRBSI14 in 6.5% (20/307) of the chlorhexidine group when compared with 11% (34/306) in the control group (P = 0.047), and dpCRBSI in 10.4% (32/307) versus 17% (52/306), respectively (P = 0.019). The frequency of dressing intolerance with cutaneous and soft tissue abnormalities at the contact area was similar in both groups (12.4% and 11.8%; P = 0.901). CONCLUSIONS: Although the trial failed its primary end point, the application of chlorhexidine containing catheter securement dressings reduces the incidence of definite or probable CRBSI in neutropenic patients. CLINICAL TRIALS NUMBER: NCT01544686 (Clinicaltrials.gov).


Asunto(s)
Infecciones Relacionadas con Catéteres/prevención & control , Catéteres Venosos Centrales/efectos adversos , Clorhexidina/administración & dosificación , Neutropenia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Vendajes , Infecciones Relacionadas con Catéteres/complicaciones , Infecciones Relacionadas con Catéteres/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neutropenia/inducido químicamente , Neutropenia/patología
9.
J Chem Phys ; 131(1): 014101, 2009 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-19586090

RESUMEN

We present a computational screening study of ternary metal borohydrides for reversible hydrogen storage based on density functional theory. We investigate the stability and decomposition of alloys containing 1 alkali metal atom, Li, Na, or K (M(1)); and 1 alkali, alkaline earth or 3d/4d transition metal atom (M(2)) plus two to five (BH(4))(-) groups, i.e., M(1)M(2)(BH(4))(2-5), using a number of model structures with trigonal, tetrahedral, octahedral, and free coordination of the metal borohydride complexes. Of the over 700 investigated structures, about 20 were predicted to form potentially stable alloys with promising decomposition energies. The M(1)(Al/Mn/Fe)(BH(4))(4), (Li/Na)Zn(BH(4))(3), and (Na/K)(Ni/Co)(BH(4))(3) alloys are found to be the most promising, followed by selected M(1)(Nb/Rh)(BH(4))(4) alloys.

10.
Br J Anaesth ; 89(6): 863-72, 2002 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12453931

RESUMEN

BACKGROUND: We describe the development and comparison of a psychometric questionnaire on patient satisfaction with anaesthesia care among six hospitals. METHODS: We used a rigorous protocol: generation of items, construction of the pilot questionnaire, pilot study, statistical analysis (construct validity, factor analysis, reliability analysis), compilation of the final questionnaire, main study, repeated analysis of construct validity and reliability. We compared the mean total problem score and the scores for the dimensions: 'Information/Involvement in decision-making', and 'Continuity of personal care by anaesthetist'. The influence of potential confounding variables was tested (multiple linear regression). RESULTS: The average problem score from all hospitals was 18.6%. Most problems are mentioned in the dimensions 'Information/Involvement in decision-making' (mean problem score: 30.9%) and 'Continuity of personal care by anaesthetist' (mean problem score: 32.2%). The overall assessment of the quality of anaesthesia care was good to excellent in 98.7% of cases. The most important dimension was 'Information/Involvement in decision-making'. The mean total problem score was significantly lower for two hospitals than the total mean for all hospitals (significantly higher at two hospitals) (P<0.05). Amongst the confounding variables considered, age, sex, subjective state of health, type of anaesthesia and level of education had an influence on the total problem score and the two dimensions mentioned. There were only marginal differences with and without the influence of the confounding variables for the different hospitals. CONCLUSIONS: A psychometric questionnaire on patient satisfaction with anaesthesia care must cover areas such as patient information, involvement in decision-making, and contact with the anaesthetist. The assessment using summed scores for dimensions is more informative than a global summed rating. There were significant differences between hospitals. Moreover, the high problem scores indicate a great potential for improvement at all hospitals.


Asunto(s)
Anestesia/normas , Satisfacción del Paciente , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Austria , Continuidad de la Atención al Paciente/normas , Femenino , Humanos , Masculino , Auditoría Médica , Persona de Mediana Edad , Participación del Paciente , Psicometría , Reproducibilidad de los Resultados , Suiza
11.
Exp Dermatol ; 11(4): 376-80, 2002 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12190948

RESUMEN

For topical treatment of androgenetic alopecia (AGA) in women, solutions containing either estradiol benzoate, estradiol valerate, 17beta- or 17alpha-estradiol are commercially available in Europe and some studies show an increased anagen and decreased telogen rate after treatment as compared with placebo. At present it is not precisely known how estrogens mediate their beneficial effect on AGA-affected hair follicles. We have shown recently that 17alpha-estradiol is able to diminish the amount of dihydrotestosterone (DHT) formed by human hair follicles after incubation with testosterone, while increasing the concentration of weaker steroids such as estrogens. Because aromatase is involved in the conversion of testosterone to estrogens and because there is some clinical evidence that aromatase activity may be involved in the pathogenesis of AGA, we addressed the question whether aromatase is expressed in human hair follicles and whether 17alpha-estradiol is able to modify the aromatase activity. Herewith we were able to demonstrate that intact, microdissected hair follicles from female donors express considerably more aromatase activity than hair follicles from male donors. Using immunohistochemistry, we detected the aromatase mainly in the epithelial parts of the hair follicle and not in the dermal papilla. Furthermore, we show that in comparison to the controls, we noticed in 17alpha-estradiol-incubated (1 nM) female hair follicles a concentration- and time-dependent increase of aromatase activity (at 24 h: 1 nM = +18%, 100 nM = +25%, 1 micro M = +57%; 24 h: 1 nM = +18%, 48 h: 1 nM = +25%). In conclusion, our ex vivo experiments suggest that under the influence of 17alpha-estradiol an increased conversion of testosterone to 17beta-estradiol and androstendione to estrone takes place, which might explain the beneficial effects of estrogen treatment of AGA.


Asunto(s)
Aromatasa/biosíntesis , Estradiol/farmacología , Folículo Piloso/efectos de los fármacos , Folículo Piloso/enzimología , Adulto , Alopecia/tratamiento farmacológico , Alopecia/enzimología , Alopecia/patología , Androstenodiona/metabolismo , Inducción Enzimática/efectos de los fármacos , Estradiol/metabolismo , Estrona/metabolismo , Femenino , Folículo Piloso/metabolismo , Humanos , Inmunohistoquímica , Técnicas In Vitro , Masculino , Testosterona/metabolismo
12.
Gesundheitswesen ; 64(7): 391-7, 2002 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-12119584

RESUMEN

OBJECTIVE: Health information for lay people in print or electronic form are internationally recognised as useful tools and as necessary in the decision-making process of individuals. The effectiveness of offered patient information depends on quality and accessibility. Because much of the available health information is significantly deficient, the Agency for Quality in Medicine developed a programme for assessing the quality of specialised health and medical information for all non-medically trained persons. The German 'Clearinghouse for Patient Information' project is an adjunct to the already established German 'Clearinghouse for Clinical Guidelines'. METHOD: The basis for quality improvement for specialised medical information consists 1. in the determination of demands on quality for patient information published in the German language, 2. development of a standardised instrument for assessing the quality of specialised medical information by non-medically trained persons, 3. establishment of an Internet portal for evaluated and rated material, and 4. the establishment and organisation of relevant partnerships with information providers and users of health and medical information. The principle building block to rate medical information for lay people are the DISCERN criteria for good patient information. The results of the quality rating of specialised medical information are made available to the public with emphasis on promoting transparency of the assessment and rating processes used. RESULTS: The Internet-based patient information service of the Agency for Quality in Medicine (www.patienten-information.de 19.06.02) has currently a selection of approximately 800 information items covering fifty disease topics with fully or partially evaluated and rated information. Partnerships to appropriate information providers and users are already established and have been tested in special single projects. CONCLUSION: To advance the process of quality improvement for medical information for non-medical and lay persons, it is essential to develop and to intensify the cooperation with stake holders and partners at different levels. Only through close cooperation with others it is possible to create a basis to continuously develop and improve the information quality assessment instrument further. In addition, effective strategies need to be developed to disseminate these endeavours to patients and consumers of health information in a user-friendly and transparent way.


Asunto(s)
Internet/normas , Computación en Informática Médica/normas , Educación del Paciente como Asunto/normas , Garantía de la Calidad de Atención de Salud/normas , Medicina Basada en la Evidencia , Alemania , Humanos , Programas Nacionales de Salud , Guías de Práctica Clínica como Asunto , Programas Informáticos
13.
Naturwissenschaften ; 87(2): 80-2, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10663139

RESUMEN

The defensive secretions of two tropical species of millipedes (the spirostreptid Telodeinopus aoutii and a species of Harpagophoridae) contain a complex mixture of closely related benzoquinones and hydroquinones. The major compounds are toluquinone and 2-methoxy-3-methylbenzoquinone, accompanied by the minor components, 2,3-dimethoxybenzoquinone and toluhydroquinone. Because of the large size and the geographic separation of the test animals a common defensive strategy of tropical, large millipedes against predation by vertebrates is assumed.


Asunto(s)
Artrópodos/fisiología , Benzoquinonas/metabolismo , Hidroquinonas/metabolismo , Animales , Benzoquinonas/química , Hidroquinonas/química , Conducta Predatoria , Clima Tropical , Vertebrados
14.
Tree Physiol ; 20(5_6): 367-381, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12651452

RESUMEN

Managing tropical rain forests is difficult because few long-term field data on forest growth and the impact of harvesting disturbance are available. Growth models may provide a valuable tool for managers of tropical forests, particularly if applied to the extended forest areas of up to 100,000 ha that typically constitute the so-called forest management units (FMUs). We used a stand growth model in a geographic information system (GIS) environment to simulate tropical rain forest growth at the FMU level. We applied the process-based rain forest growth model Formix 3-Q to the 55,000 ha Deramakot Forest Reserve (DFR) in Sabah, Malaysia. The FMU was considered to be composed of single and independent small-scale stands differing in site conditions and forest structure. Field data, which were analyzed with a GIS, comprised a terrestrial forest inventory, site and soil analyses (water, nutrients, slope), the interpretation of aerial photographs of the present vegetation and topographic maps. Different stand types were determined based on a classification of site quality (three classes), slopes (four classes), and present forest structure (four strata). The effects of site quality on tree allometry (height-diameter curve, biomass allometry, leaf area) and growth (increment size) are incorporated into Formix 3-Q. We derived allometric relations and growth factors for different site conditions from the field data. Climax forest structure at the stand level was shown to depend strongly on site conditions. Simulated successional pattern and climax structure were compared with field observations. Based on the current management plan for the DFR, harvesting scenarios were simulated for stands on different sites. The effects of harvesting guidelines on forest structure and the implications for sustainable forest management at Deramakot were analyzed. Based on the stand types and GIS analysis, we also simulated undisturbed regeneration of the logged-over forest in the DFR at the FMU level. The simulations predict slow recovery rates, and regeneration times far exceeding 100 years.

15.
Nucleic Acids Res ; 27(8): 1828-36, 1999 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-10101190

RESUMEN

By screening a rabbit reticulocyte library, an alternative 15-LOX transcript of 3.6 kb (15-LOX mRNA2) was detected containing a 1019 nt longer 3'-untranslated region (UTR2) than the main 2.6 kb mRNA (15-LOX mRNA1). In anaemic animals, northern blotting showed that 15-LOX mRNA2 was predominantly expressed in non-erythroid tissues, whereas 15-LOX mRNA1 was exclusively expressed in red blood cells and bone marrow. The 15-LOX 3'-UTR2 mRNA2 contained a novel 8-fold repetitive CU-rich motif, 23 nt in length (DICE2). This motif is related but not identical to the 10-fold repetitive differentiation control element (DICE1) of 19 nt residing in the 15-LOX UTR1 mRNA1. DICE1 was shown to interact with human hnRNP proteins E1 and K, thereby inhibiting translation. From tissues expressing the long 15-LOX mRNA2, two to three unidentified polypeptides with molecular weights of 53-55 and 90-93 kDa which bound to DICE2 were isolated by RNA affinity chromatography. A 93 kDa protein from lung cytosol, which was selected by DICE2 binding, was able to suppress translational inhibition of 15-LOX mRNA2, but not of 15-LOX mRNA1, by hnRNP E1. A possible interaction between DICE1/DICE2 cis / trans factors in translational control of 15-LOX synthesis is discussed. Furthermore, the 3'-terminal part of the highly related rabbit leukocyte-type 12-LOX gene was analysed. Very similar repetitive CU-rich elements of the type DICE1 (20 repeats) and DICE2 (nine repeats) were found in the part corresponding to the 3'-UTR of the mRNA.


Asunto(s)
Regiones no Traducidas 3' , Empalme Alternativo , Araquidonato 15-Lipooxigenasa/genética , Regulación Enzimológica de la Expresión Génica , Biosíntesis de Proteínas , Animales , Araquidonato 12-Lipooxigenasa/genética , Secuencia de Bases , Sitios de Unión , ADN Complementario , Humanos , Leucocitos/enzimología , Datos de Secuencia Molecular , ARN Mensajero , Proteínas de Unión al ARN/metabolismo , Conejos
17.
Proc Natl Acad Sci U S A ; 95(18): 10960-5, 1998 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-9724812

RESUMEN

Stroke and head trauma are worldwide public health problems and leading causes of death and disability in humans, yet, no adequate neuroprotective treatment is available for therapy. Glutamate antagonists are considered major drug candidates for neuroprotection in stroke and trauma. However, N-methyl-D-aspartate antagonists failed clinical trials because of unacceptable side effects and short therapeutic time window. alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonists derived from the quinoxalinedione scaffold cannot be used in humans because of their insolubility and resulting renal toxicity. Therefore, achieving water solubility of quinoxalinediones without loss of selectivity and potency profiles becomes a major challenge for medicinal chemistry. One of the major tenets in the chemistry of glutamate antagonists is that the incorporation of phosphonate into the glutamate framework results in preferential N-methyl-D-aspartate antagonism. Therefore, synthesis of phosphonate derivatives of quinoxalinediones was not pursued because of a predicted loss of their selectivity toward AMPA. Here, we report that introduction of a methylphosphonate group into the quinoxalinedione skeleton leaves potency as AMPA antagonists and selectivity for the AMPA receptor unchanged and dramatically improves solubility. One such novel phosphonate quinoxalinedione derivative and competitive AMPA antagonist ZK200775 exhibited a surprisingly long therapeutic time window of >4 h after permanent occlusion of the middle cerebral artery in rats and was devoid of renal toxicity. Furthermore, delayed treatment with ZK200775 commencing 2 h after onset of reperfusion in transient middle cerebral artery occlusion resulted in a dramatic reduction of the infarct size. ZK200775 alleviated also both cortical and hippocampal damage induced by head trauma in the rat. These observations suggest that phosphonate quinoxalinedione-based AMPA antagonists may offer new prospects for treatment of stroke and trauma in humans.


Asunto(s)
Trastornos Cerebrovasculares/tratamiento farmacológico , Traumatismos Craneocerebrales/tratamiento farmacológico , Antagonistas de Aminoácidos Excitadores/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Organofosfonatos/uso terapéutico , Quinoxalinas/uso terapéutico , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/antagonistas & inhibidores , Animales , Células Cultivadas , Trastornos Cerebrovasculares/fisiopatología , Traumatismos Craneocerebrales/fisiopatología , Potenciales Evocados/efectos de los fármacos , Gerbillinae , Técnicas In Vitro , Ratones , Organofosfonatos/química , Quinoxalinas/química , Ensayo de Unión Radioligante , Ratas
18.
J Mol Biol ; 278(5): 935-48, 1998 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-9600854

RESUMEN

In rabbit reticulocytes an arachidonic acid 15-lipoxygenase (15-LOX) is expressed at high yield. Rescreening a rabbit reticulocyte cDNA library for alternative 15-LOX transcripts, a full length cDNA which encodes a novel lipoxygenase was isolated. The predicted amino acid sequence of this enzyme shared a high degree (99%) of identity with the reticulocyte-type 15-lipoxygenase. Among the six amino acid residues different in both enzymes a Phe-Leu exchange was detected at position 353. Recently, site-directed mutagenesis studies have revealed that this amino acid exchange converts a 15-lipoxygenase to a 12-lipoxygenase. In fact, when the novel enzyme was expressed in Escherichia coli, mainly 12-lipoxygenation of arachidonic acid was observed. The recombinant enzyme exhibited a rather broad substrate specificity. Various C-18 and C-20 polyenoic fatty acids and even complex substrates such as biomembranes were effectively oxygenated. Thus, the novel enzyme may be classified as leukocyte-type 12-lipoxygenase. Genomic polymerase chain reaction of the 3' region of the leukocyte-type 12-lipoxygenase gene indicated that introns 10 to 13 differed to about 10% from the corresponding sequences of the 15-lipoxygenase gene although their size and the intron-exon organization were very similar. In the 3'-untranslated region of the novel mRNA a C+U-rich, 20-fold repetitive element was found which appears to be highly related to the differentiation control element of the 15-lipoxygenase mRNA. Activity assays with a variety of cells and tissues prepared from normal rabbits suggested that only peripheral monocytes abundantly express the enzyme, suggesting a tissue-specific regulation of gene expression. These data indicate for the first time the co-expression of two separate genes for a reticulocyte-type 15-lipoxygenase and for a leukocyte-type 12-lipoxygenase in one species. This is of importance for the implication of both enzymes in red blood cell development and atherogenesis.


Asunto(s)
Araquidonato 12-Lipooxigenasa/biosíntesis , Araquidonato 15-Lipooxigenasa/biosíntesis , Leucocitos/enzimología , Reticulocitos/enzimología , Secuencia de Aminoácidos , Animales , Araquidonato 12-Lipooxigenasa/genética , Araquidonato 15-Lipooxigenasa/genética , Secuencia de Bases , Clonación Molecular , ADN , Escherichia coli , Expresión Génica , Humanos , Datos de Secuencia Molecular , Conejos , Homología de Secuencia de Aminoácido
19.
J Addict Dis ; 17(2): 1-7, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9567222

RESUMEN

UNLABELLED: As dissatisfaction with unrestricted smoking in institutional settings has grown, a number of psychiatric facilities have banned smoking. A compromise, restricted smoking, was recently introduced on an inpatient psychiatric unit at a University of Michigan Hospital. The subsequent rescission of the restricted smoking policy enabled us to compare the effects of restricted smoking vs. ad lib smoking on motivation to quit smoking. METHOD: Current smokers admitted to an inpatient psychiatry unit were asked to participate in this study. As soon as possible after intake, the patient completed a smoking history questionnaire, depression and anxiety scales, and a stage of change measure. The stage of change measure was readministered upon discharge from the unit. RESULTS: Repeated measures ANOVA revealed an interaction for Condition (Restricted vs. Ad Lib) by Time (Admission vs. Discharge) for the Action scale, which assesses current level of activity in smoking cessation efforts. Restricted smokers decreased while ad lib smokers increased in motivation over time. CONCLUSIONS: Results suggest that the restricted smoking policy does not have beneficial motivational effects. Alternative strategies for controlling smoking on an inpatient psychiatric unit are suggested.


Asunto(s)
Trastornos Mentales/psicología , Motivación , Cese del Hábito de Fumar , Prevención del Hábito de Fumar , Adulto , Análisis de Varianza , Femenino , Política de Salud , Humanos , Masculino , Persona de Mediana Edad , Política Pública
20.
Cancer Genet Cytogenet ; 100(2): 129-33, 1998 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-9428356

RESUMEN

Both flow cytometry and fluorescence in situ hybridization (FISH) are useful techniques in the analysis of cancer tissues. When the two are used in the study of the same specimens, they are usually performed in parallel, separately. This is problematic where there is a scarcity of material, making completion of both studies impossible. Fluorescence in situ hybridization procedures that will utilize excess material discarded from flow cytometry would be advantageous. The present report describes an optimized protocol for performing sequential flow cytometry and FISH using formalin-fixed paraffin-embedded archival material. Although breast cancer tissues were used in this initial study, the protocol is applicable to other cancer tissues as well.


Asunto(s)
Neoplasias de la Mama/genética , Citometría de Flujo/métodos , Hibridación Fluorescente in Situ/métodos , Neoplasias de la Mama/patología , Formaldehído , Humanos , Interfase , Adhesión en Parafina
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...