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5.
Clin Neuropathol ; 29(3): 127-33, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20423685

RESUMO

OBJECTIVE: We report on a patient with pituicytoma, i.e. a rare neoplasm of the neurohypophysis, with unusual anamnestic manifestation. CASE MATERIAL: After a car accident, the patient suffered from severe persisting headaches. Diagnostic procedures revealed a minor visual impairment and restriction of the gonado- and somatotropic pituitary axis. MRI showed an architecturally solid, well demarcated and homogenous suprasellar lesion. Due to the challenging location of the lesion with a small intrasellar mass and larger suprasellar part within the hypophyseal stalk, a subtotal resection was carried out to save the pituitary function and for neuropathological assessment comprising numerous stainings and immunohistochemical reactions. We observed a highly differentiated, low proliferative, rather cellular and in individual parts moderately pleomorphic tumor with cells arranged in storiform or whorled patterns, that strongly expressed S-100 protein, microtubulus-associated protein 2 (MAP2) and vimentin. Postoperative visual field testing was inconspicuous, but pituitary malfunction was persistent. With respect to the accidental discovery of this pituicytoma, it remains unresolved whether the persisting headache was due solely to the head trauma or was additive with the effects of the pituicytoma. CONCLUSION: To date less than 30 bona fide examples have been described and typically present symptoms due to mass effects such as visual disturbances, hypopituitarism as well as interference with hypothalamic dopamine release, resulting in subsequent hyperprolactinemia accompanied by decreased libido and amenorrhea in females. These neoplasms represent an important differential diagnosis with respect to suprasellar lesions and a clinical and neuropathological challenge.


Assuntos
Adenoma/complicações , Adenoma/patologia , Traumatismos Craniocerebrais/complicações , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/patologia , Biópsia , Humanos , Achados Incidentais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
6.
Occup Environ Med ; 60(1): 69-75, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12499461

RESUMO

AIMS: To determine if exposure to dimethylisopropanolamine (DMIPA) and dimethylaminoethanol (DMAE) in a label printing plant was associated with visual disturbances and/or ocular changes. METHODS: Questionnaires, eye examinations (visual acuity, contrast sensitivity at 2.5% and 1.25% contrast, slit lamp biomicroscopy, and pachymetry), and industrial hygiene monitoring for DMIPA and DMAE were performed over a two week period. RESULTS: Eighty nine per cent of line workers reported having experienced blurry vision while at work in the past 12 months, compared to 12.5% of prime workers. A total of 108 full shift personal breathing zone (PBZ) air samples for the amines were collected. The mean time weighted average (TWA) concentration of DMIPA was significantly higher in the line division than in the prime division, as was the mean TWA concentration for total amines. The mean TWA concentration of DMAE was higher in the prime division than the line division. Higher levels of total amines were associated with increased risk of reporting blurry vision, halo vision, and blue-grey vision. The risk of corneal opacity rose with increasing exposure to total amines. The prevalence of corneal opacity also increased with increasing concentration of total amines. Median corneal thickness increased with increasing grades of corneal opacity. There was a statistically significant relation between total amine concentration and increased risk of reduced bilateral visual acuity and 2.5% contrast sensitivity. CONCLUSIONS: Exposure to tertiary amines was associated with blurry, halo, and blue-grey vision, corneal opacity, and decrements in visual acuity and contrast sensitivity at 2.5% contrast.


Assuntos
Aminas/efeitos adversos , Opacidade da Córnea/induzido quimicamente , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Visão Ocular/efeitos dos fármacos , Humanos , Impressão , Análise de Regressão , Ventilação
7.
Toxicol Appl Pharmacol ; 185(2): 128-35, 2002 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-12490137

RESUMO

As the result of a high prevalence of fixed airways obstruction in workers at a microwave popcorn manufacturing plant, we examined the hypothesis that vapors of butter flavoring used in the manufacture of microwave popcorn and other foods can produce airway injury in rats. Rats were exposed to vapors liberated from heated butter flavoring. Rats were exposed for 6 h by inhalation and were necropsied 1 day after exposure. The exposure was found by GC-MS analysis to be a complex mixture of various organic gases with the major peaks consisting of diacetyl (2,3-butanedione), acetic acid, acetoin (3-hydroxy-2-butanone), butyric acid, acetoin dimers, 2-nonanone, and delta-alkyl lactones. Diacetyl was used as a marker of exposure concentration. In the lung, butter flavoring vapors containing 285-371 ppm diacetyl caused multifocal, necrotizing bronchitis, which was most consistently present in the mainstem bronchus. Alveoli were unaffected. Butter flavoring vapors containing 203-371 ppm diacetyl caused necrosuppurative rhinitis, which affected all four levels of the nose. Within the posterior two nasal levels (T3 and T4), necrosis and inflammation was principally localized to the nasopharyngeal duct. Control rats were unaffected. Therefore, concentrations of butter flavoring vapors that can occur during the manufacture of foods are associated with epithelial injury in the nasal passages and pulmonary airways of rats.


Assuntos
Brônquios/patologia , Diacetil/toxicidade , Aromatizantes/toxicidade , Mucosa Nasal/patologia , Animais , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Histocitoquímica , Exposição por Inalação , Masculino , Microscopia Eletrônica , Líquido da Lavagem Nasal/citologia , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Necrose , Ratos , Ratos Sprague-Dawley , Organismos Livres de Patógenos Específicos
8.
Ophthalmologe ; 99(4): 295-8, 2002 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-12058507

RESUMO

INTRODUCTION: Ophthalmological examinations are important in children with suspected shaken baby and/or battered child syndrome. Retinal and epiretinal haemorrhages can indicate non-accidental injuries. We observed a case of extensive retinal hemorrhages, edema of the optic disc followed by development of optic atrophy, neovascularisation and tractional retinal detachment over the course of months. CASE REPORT: A 6-week-old infant with no history of systemic disease or trauma was admitted to the children's hospital because of a disorder of consciousness, respiratory insufficiency, taut fontanel and dilated pupils with sluggish reaction to light. A subdural haematoma was diagnosed. Ophthalmological examination showed no signs of trauma in the anterior segment. Ophthalmoscopy revealed extensive retinal haemorrhages and swollen optic nerve heads. During the next months optic atrophy, subretinal fibrosis at the posterior pole, neovascularisation at the optic disc and non-rhegmatogenous retinal detachment developed. The child is in a persistent vegetative state. DISCUSSION: Non-accidental injuries can cause direct trauma and indirect traumatic sequelae. Retinal haemorrhages, especially in conjunction with unexplained trauma or changes of consciousness should arouse suspicion of shaken baby syndrome. The ophthalmologist should emphasize this and strongly recommend further investigation if not previously undertaken.


Assuntos
Síndrome da Criança Espancada/diagnóstico , Coma/diagnóstico , Atrofia Óptica/diagnóstico , Descolamento Retiniano/diagnóstico , Hemorragia Retiniana/diagnóstico , Seguimentos , Fundo de Olho , Humanos , Lactente , Masculino , Oftalmoscopia , Disco Óptico/patologia
9.
J Med Chem ; 44(21): 3469-87, 2001 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-11585452

RESUMO

The elevated expression of cell adhesion molecules (CAMs) on the lumenal surface of vascular endothelial cells is a critical early event in the complex inflammatory process. The adhesive interactions of these CAMs that include E-selectin, ICAM-1, and VCAM-1 with their counter-receptors on leukocytes, such as integrins of the alpha(L)beta(2) family, result in migration of the leukocytes to the site of inflammation and cause tissue injury. Pharmaceutical agents that could suppress the induced expression of one or more of these cell adhesion molecules would provide a novel mechanism to attenuate the inflammatory responses associated with chronic inflammatory diseases. A-205804 (1), a potent and selective inhibitor of the induced expression of E-selectin and ICAM-1 over VCAM-1, was further modified with emphasis at the C-4 and C-2 positions to identify a more potent drug candidate with a good pharmacokinetic profile and physical properties. Replacement of the C-4 sulfur linkage in 1 with an oxygen atom eliminated one of the two major metabolites for this lead molecule. The para-position of the 4-phenoxy group of the thieno[2,3-c]pyridine lead is found to be very critical for a higher in vitro potency and selectivity of E-selectin and ICAM-1 over VCAM-1 expression. This position is presumably close to the solvent-accessible region of the target protein-inhibitor complex. An attempt to install a water-solubilizing group at the para-position of the phenoxy group to increase the aqueous solubility of this lead series through various linkages failed to provide an ideal inhibitor. Only small substituents such as fluorine are tolerated at the meta- and ortho-positions of the 4-phenoxy to retain a good in vitro potency. Bromo, trifluoromethyl, pyrazol-1-yl, and imidazol-1-yl are among the better substituents at the para-position. With fine-tuning at the C-2 position we discovered a series of very potent (IC(50) < 5 nM for ICAM-1) and selective (>200-fold vs VCAM-1) inhibitors with a good pharmacokinetic profile. Demonstrated efficacy in a rat rheumatoid arthritis model and in a mice asthma model with selected compounds is also reported.


Assuntos
Antiasmáticos/síntese química , Anti-Inflamatórios não Esteroides/síntese química , Selectina E/metabolismo , Endotélio Vascular/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Piridinas/síntese química , Animais , Antiasmáticos/química , Antiasmáticos/farmacocinética , Antiasmáticos/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/farmacologia , Artrite Experimental/tratamento farmacológico , Asma/tratamento farmacológico , Células Cultivadas , Depressão Química , Endotélio Vascular/citologia , Ensaio de Imunoadsorção Enzimática , Hepatócitos/metabolismo , Humanos , Masculino , Camundongos , Piridinas/química , Piridinas/farmacocinética , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/farmacologia , Veias Umbilicais
10.
J Med Chem ; 44(6): 988-1002, 2001 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-11300880

RESUMO

A critical early event in the inflammatory cascade is the induced expression of cell adhesion molecules on the lumenal surface of vascular endothelial cells. These adhesion molecules include E-selectin, ICAM-1, and VCAM-1, which serve to recruit circulating leukocytes to the site of the inflammation. These adhesive interactions allow the leukocytes to firmly adhere to and cross the vascular endothelium and migrate to the site of tissue injury. Pharmaceutical agents which would prevent the induced expression of one or more of the cell adhesion molecules on the endothelium might be expected to provide a novel mechanism to attenuate the inflammatory responses associated with chronic inflammatory diseases. A thieno[2,3-d]pyrimidine, A-155918, was identified from a whole-cell high-throughput assay for compounds which inhibited the tumor necrosis factor-alpha (TNFalpha)-induced expression of E-selectin, ICAM-1, or VCAM-1 on human vascular endothelial cells. Traditional medicinal chemistry methods were applied to this low-micromolar inhibitor, resulting in the 2,4-disubstituted thieno[2,3-c]pyridine A-205804, a potent and selective lead inhibitor of E-selectin and ICAM-1 expression (IC(50) = 20 and 25 nM, respectively). The relative position of the nitrogen atom in the thienopyridine isomer was shown to be critical for activity, as was a small amide 2-substituent.


Assuntos
Selectina E/metabolismo , Endotélio Vascular/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/metabolismo , Pirimidinas/síntese química , Administração Oral , Animais , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Depressão Química , Selectina E/genética , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Ensaio de Imunoadsorção Enzimática , Genes Reporter , Humanos , Molécula 1 de Adesão Intercelular/genética , Luciferases/genética , Regiões Promotoras Genéticas , Pirimidinas/química , Pirimidinas/farmacologia , Pirimidinas/toxicidade , Ratos , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/farmacologia , Veias Umbilicais/citologia , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
13.
Toxicol Appl Pharmacol ; 143(1): 37-46, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9073590

RESUMO

Following a formulation change, a leather conditioner was involved in a 1992 nationwide outbreak of respiratory illness. We investigated the composition and toxicity of the conditioner produced before (previous product) and after (new product) the disease outbreak. The new product induced tachypnea, pulmonary edema, pulmonary hemorrhage, and sporadic deaths in exposed guinea pigs and rats. Ultrastructurally, these changes were associate with direct pulmonary cytotoxicity characterized by necrosis of alveolar type I cells and alveolar septal interstitial edema. Chemical analyses suggested major alterations in the fluorohydrocarbon constituents in the new formulation of the leather conditioner. While these alterations could not be specifically identified, they appeared to include changes from fluoralkanes to fluoroalkenes, fluorophenyl, and/or fluoroalcohol compounds. Changes in solvent composition were consistent with traces of 2-butoxyethanol and isomers of dipropylene glycol methyl ether, and additional C10-C12 alkanes. In this study, we demonstrated the toxicity of the new product in laboratory animals. Some of the altered constituents of the new product have been identified and are potential candidates for additional investigations to identify specific etiologic agents.


Assuntos
Acetatos/toxicidade , Etilenoglicóis/toxicidade , Fluorocarbonos/toxicidade , Pneumopatias/induzido quimicamente , Propano/toxicidade , Propilenoglicóis/toxicidade , Solventes/toxicidade , Aerossóis , Animais , Líquido da Lavagem Broncoalveolar/citologia , Epitélio/ultraestrutura , Junções Comunicantes/ultraestrutura , Cobaias , Hemorragia/induzido quimicamente , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pneumopatias/patologia , Masculino , Microscopia Eletrônica , Necrose , Alvéolos Pulmonares/ultraestrutura , Ratos , Ratos Sprague-Dawley , Organismos Livres de Patógenos Específicos , Curtume
15.
Ophthalmologe ; 93(3): 284-91, 1996 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-8753993

RESUMO

In a retrospective study of 15 patients with epithelial and non-epithelial masses of the lacrimal gland, the value of high-resolution computed tomography (CT) with multiplanar and three-dimensional reconstructions was compared to magnetic resonance imaging (MRI). For the differential diagnosis of lacrimal gland lesions the following parameters are important: shape of the lacrimal gland, internal structure, degree of contrast enhancement and integrity of adjacent bony structures. In evaluation of the extent of lacrimal gland lesions, thin-section CT with multiplanar and three-dimensional reconstruction is equal to MRI, while spiral CT with 1-mm slices is superior to standard CT with 2-mm slices. However, internal structure and contrast enhancement of lacrimal glands, integrity of adjacent bones and intracranial infiltration are better visualized with MRI than with CT. Only inhomogeneous mixed tissue tumors can be differentiated from homogeneous tumors by CT due to density differences. In conclusion, MRI is the method of choice if lacrimal gland tumors are suspected, while CT is only useful in doubtful cases concerning the bony structures as an additional method. Using modern imaging modalities, differentiation between epithelial and non-epithelial masses is possible for further diagnosis and therapeutic decisions. Both pleomorphic adenoma due to its different dense components and malignant masses due to bony destruction and intracranial attachment can be differentiated and treated in a specific way. Differentiation between non-epithelial masses (lymphoma and inflammatory pseudotumor) is only possible with a combination of imaging, clinical appearance and in some cases biopsy.


Assuntos
Neoplasias Oculares/diagnóstico , Processamento de Imagem Assistida por Computador , Doenças do Aparelho Lacrimal/diagnóstico , Imageamento por Ressonância Magnética/instrumentação , Tomografia Computadorizada por Raios X/instrumentação , Adolescente , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Aparelho Lacrimal/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
16.
Ophthalmologe ; 93(3): 292-8, 1996 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-8753994

RESUMO

Because of its high soft tissue resolution and its lack of radiation hazard, MRI is considered a valuable method in the diagnosis of orbital disease. Insufficient spatial resolution was considered the main drawback of orbital MRI. Another problem was the chemical shift artifact caused by shifting of the signal of fat and water. To optimize image quality, a high-resolution coil with a small diameter was constructed. Twenty patients with intraorbital changes were examined with MRI. We used a special surface coil with a diameter of 4 cm. For optimal image quality we modified the bandwidth and other parameters of the sequences. For comparison additional measurements were performed in 13 patients with the standard surface coil (diameter 11 cm) and/or the head coil. The best results were obtained with a middle bandwidth (78 Hz); the chemical shift was reduced significantly. Little motion artifacts are visible in every examination caused by involuntary eye movements, which led to evaluation limitations in 3 cases. Compared to the examination with normal coils, the detection of details was much better. In 3 cases small changes were only found with the high-resolution orbital coil. With the high-resolution surface coil it is possible to examine the orbit. It is like looking through a magnifying glass. Using an optimized bandwidth, both the signal-to-noise and the chemical shift are acceptable. The new orbital coil is especially useful for the detection of small orbital lesions.


Assuntos
Aumento da Imagem/instrumentação , Imageamento por Ressonância Magnética/instrumentação , Doenças Orbitárias/diagnóstico , Neoplasias Orbitárias/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Olho/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Órbita/patologia , Estudos Prospectivos
17.
Ophthalmologe ; 93(1): 3-7, 1996 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-8867152

RESUMO

Cataract surgery can be combined with the correction of high preoperative astigmatism by using a corneal tunnel incision in the steep meridian. We examined 37 patients (mean age 70 years) with cataract and a mean preoperative astigmatism of 3.6 D (2.0-4.75 D). A 7-mm clear corneal incision was made for phacoemulsification and thus a reduction in the astigmatism was achieved. The mean induced astigmatism was 3.6 D (SD 1.6 D minium 0.8 D, maximum 7.5 D) on the first postoperative day and 2.7 D (SD 0.9 D, minimum 1.6 D, maximum 4.9 D) after 10 months. By modification of the incision technique with a trapezoidal corneal incision and a single radial suture the wound closure was more stable, but the astigmatic correction did not change significantly compared to the results after the original 7-mm clear corneal incision technique.


Assuntos
Lentes Intraoculares , Facoemulsificação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Astigmatismo/etiologia , Astigmatismo/cirurgia , Córnea/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
18.
Aktuelle Radiol ; 5(6): 363-6, 1995 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-8580134

RESUMO

In an extended case report, we discuss four cases with masses in the lacrimal fossa representing the most important entities in this region (lymphoma, pleomorphadenoma, inflammatory pseudotumor, and malignant epithelial tumor). The different indications for CT and MRI are explained. For the differential diagnosis of lacrimal gland lesions, the following imaging parameters are important: the shape of the lacrimal gland, the inner structure, the degree of contrast enhancement, and the surrounding bony structures. In the evaluation of the expansion of lacrimal gland lesions, CT in thin slices with multiplanar reconstructions is equal to MRI. However, the contrast-enhancement of lacrimal glands is better evaluated with MRI than with CT. The bony structures are better visualized on CT than on MRI.


Assuntos
Neoplasias Oculares/diagnóstico , Doenças do Aparelho Lacrimal/diagnóstico , Imageamento por Ressonância Magnética , Lesões Pré-Cancerosas/diagnóstico , Tomografia Computadorizada por Raios X , Adenoma Pleomorfo/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Exoftalmia/etiologia , Feminino , Humanos , Aparelho Lacrimal/patologia , Linfoma/diagnóstico , Masculino , Pessoa de Meia-Idade , Pseudotumor Orbitário/diagnóstico
19.
Exp Clin Endocrinol ; 102(5): 399-408, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7867704

RESUMO

The catechol estrogens (CE), 2-hydroxyestradiol (2-OH-E2) and 4-hydroxyestradiol (4-OH-E2) were analyzed for their binding affinity to the estrogen receptor of MCF-7 cells. Applying a competitive binding assay to cytosols prepared from MCF-7 breast cancer cells, we measured a relative binding affinity of 23% (2-OH-E2) and 26% (4-OH-E2) compared to E2. Nuclear binding assays with the same cell line demonstrated a high specific binding with Kd's of 0.31 nM (2-OH-E2) and 0.21 nM (4-OH-E2). The relative binding affinity measured was 25% and 42% for 2-OH-E2 and 4-OH-E2, respectively. Based on this nuclear binding it can be concluded that the estrogen receptor occupied by CE is bound within the nucleus and might therefore be transcriptionally active.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Estradiol/análogos & derivados , Receptores de Estrogênio/metabolismo , Ligação Competitiva , Neoplasias da Mama/ultraestrutura , Núcleo Celular/química , Núcleo Celular/metabolismo , Núcleo Celular/ultraestrutura , Citosol/química , Citosol/metabolismo , Citosol/ultraestrutura , Estradiol/análise , Estradiol/isolamento & purificação , Estradiol/metabolismo , Estrogênios de Catecol/análise , Estrogênios de Catecol/isolamento & purificação , Estrogênios de Catecol/metabolismo , Humanos , Prolactina/metabolismo , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Células Tumorais Cultivadas
20.
Klin Monbl Augenheilkd ; 201(1): 48-50, 1992 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-1513127

RESUMO

A two-year-old boy with nephropathic cystinosis was successfully treated with cysteamine eye drops. Using topical cysteamine 0.1% every two hours in the right eye we found a clearance of crystals from the cornea after 26 weeks. In the left eye, treated with topical cysteamine 0.5% the same result was reached after 12 weeks.


Assuntos
Opacidade da Córnea/tratamento farmacológico , Cisteamina/administração & dosagem , Cistina/metabolismo , Cistinose/tratamento farmacológico , Pré-Escolar , Córnea/patologia , Opacidade da Córnea/patologia , Cristalização , Cistinose/patologia , Humanos , Masculino , Soluções Oftálmicas
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