MR of CNS sarcoidosis: correlation of imaging features to clinical symptoms and response to treatment.
(17/3349)
BACKGROUND AND PURPOSE: Sarcoidosis is an idiopathic systemic granulomatous disease, recognized in a patient when clinical and radiologic findings are confirmed by histopathologic analysis. The objective was to identify a relationship between MR imaging and clinical findings in CNS sarcoidosis. METHODS: The clinical charts of 461 patients with biopsy-proved sarcoidosis were reviewed retrospectively. Criteria for including patients in the study included those with symptoms referable to the CNS, excluding those with another explanation for their symptoms, those with headaches or other subjective complaints without accompanying objective findings, and those with peripheral neuropathy other than cranial nerve involvement or myopathy without CNS manifestations. Thirty-four of 38 patients whose conditions met the criteria for CNS sarcoidosis underwent a total of 82 MR examinations. The positive imaging findings were divided into categories as follows: pachymeningeal, leptomeningeal, nonenhancing brain parenchymal, enhancing brain parenchymal, cranial nerve, and spinal cord and nerve root involvement. Treatment response, clinical symptomatology, and any available histopathologic studies were analyzed with respect to imaging manifestations in each of the categories. RESULTS: Eighty-two percent of the patients with sarcoidosis with neurologic symptoms referable to the CNS had findings revealed by MR imaging. However, eight (40%) of 20 cranial nerve deficits seen at clinical examination of 13 patients were not seen at contrast-enhanced MR imaging, and 50% of the patients with symptoms referable to the pituitary axis had no abnormal findings on routine contrast-enhanced MR images. In contradistinction, 44% of 18 cranial nerves in nine patients with MR evidence of involvement had no symptoms referable to the involved cranial nerve. Clinical and radiologic deterioration occurred more commonly with leptomeningeal and enhancing brain parenchymal lesions. CONCLUSION: MR imaging can be used to confirm clinical suspicion and to show subclinical disease and the response of pathologic lesions to treatment. (+info)
Epidurography and therapeutic epidural injections: technical considerations and experience with 5334 cases.
(18/3349)
BACKGROUND AND PURPOSE: Even in experienced hands, blind epidural steroid injections result in inaccurate needle placement in up to 30% of cases. The use of fluoroscopy and radiologic contrast material provides confirmation of accurate needle placement within the epidural space. We describe our technique and experience with contrast epidurography and therapeutic epidural steroid injections, and review the frequency of systemic and neurologic complications. METHODS: Epidural steroid injections were performed in 5489 consecutive outpatients over a period of 5 1/2 years by three procedural neuroradiologists. In 155 cases (2.8%), the injections were done without contrast material owing to either confirmed or suspected allergy. The remaining 5334 injections were performed after epidurography through the same needle. Patients and referring clinicians were instructed to contact us first regarding complications or any problem potentially related to the injection. In addition, the referring clinicians' offices were instructed to contact us regarding any conceivable procedure-related complications. RESULTS: Only 10 patients in the entire series required either oral (n = 5) or intravenous (n = 5) sedation. Four complications (0.07%) required either transport to an emergency room (n = 2) or hospitalization (n = 2). None of the complications required surgical intervention, and all were self-limited with regard to symptoms and imaging manifestations. Fluoroscopic needle placement and epidurography provided visual confirmation of accurate needle placement, distribution of the injectate, and depiction of epidural space disease. CONCLUSION: Epidurography in conjunction with epidural steroid injections provides for safe and accurate therapeutic injection and is associated with an exceedingly low frequency of untoward sequelae. It can be performed safely on an outpatient basis and does not require sedation or special monitoring. (+info)
Aromatase activity of human granulosa cells in vitro: effects of gonadotrophins and follicular fluid.
(19/3349)
The aim of this study was to assess whether human dominant follicular fluid has the ability to modulate aromatase activity and/or granulosa cell proliferation. Dominant follicular fluid was obtained by laparoscopy before the luteinizing hormone surge in naturally cycling women while granulosa cells used in the tests were obtained from in-vitro fertilization patients. Aromatase was measured by the tritiated water release assay, following a 48 h incubation with follicular fluid and serum, and expressed for 5x10(4) granulosa cells. The effects of a range of follicular fluid or serum concentrations (2.5, 5, 10 and 20%) were compared. A decrease in aromatase activity was observed when high follicular fluid concentrations (20%) (P < 0.01) were added. Low concentrations (2.5%) of follicular fluid significantly increased cell proliferation (P < 0.01) as compared to basal values (0%). No further stimulation was however observed when concentrations increased up to 20%. Further characterization of these compounds is required to understand how they may modulate maturation of the dominant follicle. (+info)
Activation of cardiac aldosterone production in rat myocardial infarction: effect of angiotensin II receptor blockade and role in cardiac fibrosis.
(20/3349)
BACKGROUND: This study analyzed the regulation and the role of the cardiac steroidogenic system in myocardial infarction (MI). METHODS AND RESULTS: Seven days after MI, rats were randomized to untreated infarcted group or spironolactone- (20 and 80 mg x kg-1 x d-1), losartan- (8 mg x kg-1 x d-1), spironolactone plus losartan-, and L-NAME- (5 mg x kg-1 x d-1) treated infarcted groups for 25 days. Sham-operated rats served as controls. In the noninfarcted myocardium of the left ventricle (LV), MI raised aldosterone synthase mRNA (the terminal enzyme of aldosterone synthesis) by 2. 0-fold and the aldosterone level by 3.7-fold. Conversely, MI decreased 11beta-hydroxylase mRNA (the terminal enzyme of corticosterone synthesis) by 2.4-fold and the corticosterone level by 1.9-fold. MI also induced a 1.9-fold increase in cardiac angiotensin II level. Such cardiac regulations were completely prevented by treatment of the infarcted heart with losartan. The MI-induced collagen deposition in noninfarcted LV myocardium was prevented by 1.6-fold by both low and high doses of spironolactone and by 2.5-fold by losartan. In addition, norepinephrine level was unchanged in infarcted heart but was attenuated by both losartan and spironolactone treatments. CONCLUSIONS: MI is associated with tissue-specific activation of myocardial aldosterone synthesis. This increase is mediated primarily by cardiac angiotensin II via AT1-subtype receptor and may be involved in post-MI ventricular fibrosis and in control of tissue norepinephrine concentration. (+info)
Fecal steroid excretion is increased in rats by oral administration of gymnemic acids contained in Gymnema sylvestre leaves.
(21/3349)
Gymnemic acids are the saponins with a triterpenoid structure contained in Gymnema sylvestre leaves and have the hypoglycemic effects. In spite of the cholesterol-binding properties of saponins, the effect of gymnemic acids on cholesterol metabolism has not been elucidated to date. We investigated the effects of gymnemic acids on fecal steroid excretion in rats. Three kinds of extracts from Gymnema sylvestre leaves, extract (GSE), acid precipitate (GSA) and column fractionate (GSF), of which the gymnemagenin (an aglycone of gymnemic acids) concentrations are 58.87, 161.6, and 363.3 mg/g respectively, were used for the experiments. These were administered to rats orally at the dose of 0.05-1.0 g/kg for 22 d. Rats were given free access to water and nonpurified diet without cholesterol, and the differences in fecal excretion of steroids and gymnemic acids were investigated. Although there were no significant effects of GSE, GSA and GSF decreased body weight gain and food intakes in a dose-dependent manner (P < 0.01). GSF (1.0 g/kg) significantly increased fecal excretion of neutral steroids and bile acids in a dose-dependent manner (P < 0.05), especially those of cholesterol and cholic acid (CA)-derived bile acids. The increases in fecal steroid excretion of cholesterol, total neutral steroids, total bile acids and CA-related bile acids were acute and significantly correlated with fecal gymnemagenin levels (r2 = 0.2316-0.9861, P < 0. 05). These results demonstrated for the first time that a high dose of gymnemic acids increases fecal cholesterol and CA-derived bile acid excretion. Further studies are needed to clarify the effect of gymnemic acids on cholesterol metabolism. (+info)
Early alterations of lung injury following acute smoke exposure and 21-aminosteroid treatment.
(22/3349)
In a simulated fire-related smoke exposure protocol, New Zealand white rabbits were utilized to investigate the potential effects of the 21-aminosteroid (lazaroid) analog U75412E on the early events of acute lung injury. Inhalation of a total of 1.6 mg/kg U75412E aerosolized at a rate of 1.53 mg/min at 0.5 hr after smoke exposure significantly attenuated the extent of lung injury at 1 hr, as evidenced by decreased bronchoalveolar lavage (BAL) concentration of total protein, 6-keto-prostaglandin F1-alpha, and blood gas defect. Histopathologic examination demonstrated that the lazaroid significantly attenuated smoke-induced lung injury as evidenced by a decrease in wet lung/body weight ratio, necrosis, and sloughing of airway epithelial cells. Electron microscopy showed that the lazaroid decreased smoke-induced interstitial edema and the vacuolization of alveolar type II epithelium (21.6 +/- 9.7 vs 8.5 +/- 3.6 vacuoled blebs/cell, smoke only vs smoke + lazaroid). However, U75412E did not attenuate smoke-induced changes in BAL concentration of tumor necrosis factor-alpha, total cell count, and granulocyte percentage. These observations suggest that U75412E may exert its action through cooperative mechanisms, such as the modulation of arachidonic acid metabolism, in addition to its characterized antioxidative effects. (+info)
Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1.
(23/3349)
We have isolated a novel liver-specific organic anion transporter, LST-1, that is expressed exclusively in the human, rat, and mouse liver. LST-1 is a new gene family located between the organic anion transporter family and prostaglandin transporter. LST-1 transports taurocholate (Km = 13.6 microM) in a sodium-independent manner. LST-1 also shows broad substrate specificity. It transports conjugated steroids (dehydroepiandrosterone sulfate, estradiol-17beta-glucuronide, and estrone-3-sulfate), eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, leukotriene E4), and thyroid hormones (thyroxine, Km = 3.0 microM and triiodothyronine, Km = 2.7 microM), reflecting hepatic multispecificity. LST-1 is probably the most important transporter in human liver for clearance of bile acids and organic anions because hepatic levels of another organic anion transporter, OATP, is very low. This is also the first report of the human molecule that transports thyroid hormones. (+info)
Cloning and characterization of a novel human olfactory UDP-glucuronosyltransferase.
(24/3349)
Xenobiotic metabolizing enzymes in the olfactory epithelium have been suggested to catalyse inactivation and facilitate elimination of odorants. We report here the molecular cloning and functional characterization of a human olfactory UDP-glucuronosyltransferase (UGT). The cloned protein is composed of 527 amino acids with an identity of 87% with a rat olfactory UGT and of 43-62% with other human UGT isoforms. Based on the sequence homology, it has been designated hUGT2A1. The gene was mapped to chromosome 4q13 by fluorescence in situ hybridization. The expression appeared to be specific for the olfactory tissue. The substrate specificity of this isoform was assessed using Chinese hamster V79 cells stably transfected with the isolated cDNA. The expressed enzyme showed a broad substrate spectrum including a range of phenolic compounds as well as aliphatic and monoterpenoid alcohols, among them many odorants. Furthermore, some steroids, especially androgens, some drugs and carcinogens were conjugated. The results support a role of the enzyme in olfactory perception and in protection of the neural system against airborne hazardous chemicals. (+info)