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5.
Clin Neuropathol ; 29(3): 127-33, 2010.
Article in English | MEDLINE | ID: mdl-20423685

ABSTRACT

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.


Subject(s)
Adenoma/complications , Adenoma/pathology , Craniocerebral Trauma/complications , Pituitary Neoplasms/complications , Pituitary Neoplasms/pathology , Biopsy , Humans , Incidental Findings , Magnetic Resonance Imaging , Male , Middle Aged
6.
Occup Environ Med ; 60(1): 69-75, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12499461

ABSTRACT

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.


Subject(s)
Amines/adverse effects , Corneal Opacity/chemically induced , Occupational Diseases/chemically induced , Occupational Exposure/adverse effects , Vision, Ocular/drug effects , Humans , Printing , Regression Analysis , Ventilation
7.
Toxicol Appl Pharmacol ; 185(2): 128-35, 2002 Dec 01.
Article in English | MEDLINE | ID: mdl-12490137

ABSTRACT

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.


Subject(s)
Bronchi/pathology , Diacetyl/toxicity , Flavoring Agents/toxicity , Nasal Mucosa/pathology , Animals , Bronchi/drug effects , Bronchi/metabolism , Bronchoalveolar Lavage Fluid/cytology , Cell Count , Histocytochemistry , Inhalation Exposure , Male , Microscopy, Electron , Nasal Lavage Fluid/cytology , Nasal Mucosa/drug effects , Nasal Mucosa/metabolism , Necrosis , Rats , Rats, Sprague-Dawley , Specific Pathogen-Free Organisms
8.
Ophthalmologe ; 99(4): 295-8, 2002 Apr.
Article in German | MEDLINE | ID: mdl-12058507

ABSTRACT

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.


Subject(s)
Battered Child Syndrome/diagnosis , Coma/diagnosis , Optic Atrophy/diagnosis , Retinal Detachment/diagnosis , Retinal Hemorrhage/diagnosis , Follow-Up Studies , Fundus Oculi , Humans , Infant , Male , Ophthalmoscopy , Optic Disk/pathology
9.
J Med Chem ; 44(21): 3469-87, 2001 Oct 11.
Article in English | MEDLINE | ID: mdl-11585452

ABSTRACT

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.


Subject(s)
Anti-Asthmatic Agents/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , E-Selectin/metabolism , Endothelium, Vascular/metabolism , Intercellular Adhesion Molecule-1/metabolism , Pyridines/chemical synthesis , Animals , Anti-Asthmatic Agents/chemistry , Anti-Asthmatic Agents/pharmacokinetics , Anti-Asthmatic Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Arthritis, Experimental/drug therapy , Asthma/drug therapy , Cells, Cultured , Depression, Chemical , Endothelium, Vascular/cytology , Enzyme-Linked Immunosorbent Assay , Hepatocytes/metabolism , Humans , Male , Mice , Pyridines/chemistry , Pyridines/pharmacokinetics , Pyridines/pharmacology , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/pharmacology , Umbilical Veins
10.
J Med Chem ; 44(6): 988-1002, 2001 Mar 15.
Article in English | MEDLINE | ID: mdl-11300880

ABSTRACT

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.


Subject(s)
E-Selectin/metabolism , Endothelium, Vascular/drug effects , Intercellular Adhesion Molecule-1/metabolism , Pyrimidines/chemical synthesis , Administration, Oral , Animals , Cell Adhesion/drug effects , Cell Line , Depression, Chemical , E-Selectin/genetics , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Enzyme-Linked Immunosorbent Assay , Genes, Reporter , Humans , Intercellular Adhesion Molecule-1/genetics , Luciferases/genetics , Promoter Regions, Genetic , Pyrimidines/chemistry , Pyrimidines/pharmacology , Pyrimidines/toxicity , Rats , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/pharmacology , Umbilical Veins/cytology , Vascular Cell Adhesion Molecule-1/genetics , Vascular Cell Adhesion Molecule-1/metabolism
13.
Toxicol Appl Pharmacol ; 143(1): 37-46, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9073590

ABSTRACT

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.


Subject(s)
Acetates/toxicity , Ethylene Glycols/toxicity , Fluorocarbons/toxicity , Lung Diseases/chemically induced , Propane/toxicity , Propylene Glycols/toxicity , Solvents/toxicity , Aerosols , Animals , Bronchoalveolar Lavage Fluid/cytology , Epithelium/ultrastructure , Gap Junctions/ultrastructure , Guinea Pigs , Hemorrhage/chemically induced , Lung/drug effects , Lung/pathology , Lung Diseases/pathology , Male , Microscopy, Electron , Necrosis , Pulmonary Alveoli/ultrastructure , Rats , Rats, Sprague-Dawley , Specific Pathogen-Free Organisms , Tanning
15.
Ophthalmologe ; 93(3): 284-91, 1996 Jun.
Article in German | MEDLINE | ID: mdl-8753993

ABSTRACT

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.


Subject(s)
Eye Neoplasms/diagnosis , Image Processing, Computer-Assisted , Lacrimal Apparatus Diseases/diagnosis , Magnetic Resonance Imaging/instrumentation , Tomography, X-Ray Computed/instrumentation , Adolescent , Adult , Aged , Diagnosis, Differential , Female , Humans , Lacrimal Apparatus/pathology , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity
16.
Ophthalmologe ; 93(3): 292-8, 1996 Jun.
Article in German | MEDLINE | ID: mdl-8753994

ABSTRACT

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.


Subject(s)
Image Enhancement/instrumentation , Magnetic Resonance Imaging/instrumentation , Orbital Diseases/diagnosis , Orbital Neoplasms/diagnosis , Adolescent , Adult , Aged , Child , Child, Preschool , Eye/pathology , Female , Humans , Male , Middle Aged , Orbit/pathology , Prospective Studies
17.
Ophthalmologe ; 93(1): 3-7, 1996 Feb.
Article in German | MEDLINE | ID: mdl-8867152

ABSTRACT

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.


Subject(s)
Lenses, Intraocular , Phacoemulsification/methods , Adult , Aged , Aged, 80 and over , Astigmatism/etiology , Astigmatism/surgery , Cornea/surgery , Female , Humans , Male , Middle Aged , Postoperative Complications/etiology , Treatment Outcome
18.
Aktuelle Radiol ; 5(6): 363-6, 1995 Nov.
Article in German | MEDLINE | ID: mdl-8580134

ABSTRACT

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.


Subject(s)
Eye Neoplasms/diagnosis , Lacrimal Apparatus Diseases/diagnosis , Magnetic Resonance Imaging , Precancerous Conditions/diagnosis , Tomography, X-Ray Computed , Adenoma, Pleomorphic/diagnosis , Adult , Aged , Diagnosis, Differential , Exophthalmos/etiology , Female , Humans , Lacrimal Apparatus/pathology , Lymphoma/diagnosis , Male , Middle Aged , Orbital Pseudotumor/diagnosis
19.
Exp Clin Endocrinol ; 102(5): 399-408, 1994.
Article in English | MEDLINE | ID: mdl-7867704

ABSTRACT

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.


Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Estradiol/analogs & derivatives , Receptors, Estrogen/metabolism , Binding, Competitive , Breast Neoplasms/ultrastructure , Cell Nucleus/chemistry , Cell Nucleus/metabolism , Cell Nucleus/ultrastructure , Cytosol/chemistry , Cytosol/metabolism , Cytosol/ultrastructure , Estradiol/analysis , Estradiol/isolation & purification , Estradiol/metabolism , Estrogens, Catechol/analysis , Estrogens, Catechol/isolation & purification , Estrogens, Catechol/metabolism , Humans , Prolactin/metabolism , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Receptors, Progesterone/metabolism , Tumor Cells, Cultured
20.
Klin Monbl Augenheilkd ; 201(1): 48-50, 1992 Jul.
Article in German | MEDLINE | ID: mdl-1513127

ABSTRACT

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.


Subject(s)
Corneal Opacity/drug therapy , Cysteamine/administration & dosage , Cystine/metabolism , Cystinosis/drug therapy , Child, Preschool , Cornea/pathology , Corneal Opacity/pathology , Crystallization , Cystinosis/pathology , Humans , Male , Ophthalmic Solutions
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