Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulation of eosinophils in the bronchial tissue occurs in a variety of inflammatory disorders of the human airway. We asked whether airway epithelial cells released factors that could influence eosinophil survival and thus contribute to accumulation of these cells in the tissues. Using conditioned medium (CM) generated from cultured human bronchial epithelial cells (HBEC), we examined the in vitro survival of eosinophils isolated from human peripheral blood. When cultured in control medium, more than 90% of the eosinophils were dead by day 4. In contrast, culture in HBEC-CM resulted in dose-dependent survival at day 6 of 69 +/- 9.4%, 40.5 +/- 5.9%, and 25 +/- 2% viability with 2, 0.5, and 0.1% HBEC-CM, respectively (n = 4). Granulocyte/macrophage colony-stimulating factor (GM-CSF) was detected in the HBEC-CM by enzyme-linked immunosorbent assay at levels of 22 to 48 pg/ml. Furthermore, preincubation of the HBEC-CM with a neutralizing monoclonal antibody to human GM-CSF completely inhibited this increased survival of eosinophils. Because corticosteroids are potent eosinopenic agents, we also examined the effects of the synthetic steroid budesonide on this system. Budesonide inhibited both spontaneous and interleukin-1 (IL-1)-induced GM-CSF production by cultured HBEC. In addition, preincubation of eosinophils with budesonide caused marked abrogation of the survival induced subsequently with either HBEC-CM or recombinant human GM-CSF. In summary, HBEC can support eosinophil survival via the elaboration of GM-CSF and thus may contribute to the local control of inflammatory cell accumulation. Steroids may modulate this process both by inhibiting cytokine production from HBEC and by a direct effect on eosinophils, preventing their response to cytokines.
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PMID:Promotion of eosinophil survival by human bronchial epithelial cells and its modulation by steroids. 205 93

Guillain-Barre syndrome is known as one of the autoimmune disease, but the etiology, pathophysiology relating immune reaction, as well as the treatment are not established. It still causes physical handicap although its rate is low. The causes, clinical symptoms and outcome of 132 cases of Guillain-Barre syndrome have been analyzed. The patients' ages ranged from 4 months to 15 years. The antecedent events for 56.1% of the patients were known. These were upper respiratory tract infection, unexplained fever, vomiting, diarrhea, vaccination, measles, german measles, shigellosis, mumps, hepatitis, pertussis and surgery in order of frequency. The CSF protein level reached a maximum at 12.3 +/- 9.5 days. Steroids did not influence the outcome of this disease. More studies are necessary to conquer the disease.
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PMID:Guillain-Barre syndrome in Korean children. 274 76

Tuberculosis meningitis (TBM) is the most serious form of infection with Mycobacterium tuberculosis. Between 1968 and 1986 15 children (five boys and 10 girls) were seen at the Royal Hospital for Sick Children, Glasgow, because of TBM. Fourteen children were Caucasian and one was Asian. The mean age at presentation was two years. None had been given BCG vaccination. In 12 children close contact with other cases of tuberculosis was reported. The signs and symptoms which helped in the diagnosis are discussed together with the initial CSF findings, results of mantoux testing and chest X-rays. Three children had unusual modes of presentation. All children were treated with chemotherapy though the drug combinations, route of administration and therapy varied from case to case. Steroids were used in nine children. Five children required neurosurgical intervention. Two children died and of the survivors six had serious sequelae. Five children made a complete recovery. The outcome of TBM depended on the duration of symptoms prior to the onset of therapy, on the neurological status reached at the time of diagnosis and the age of the child. The roles of chemotherapy, steroids and neurosurgery in the management of TBM are discussed. The need for routine BCG vaccination of all neonates is examined.
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PMID:Tuberculous meningitis in children: a review of 15 cases. 338 99

Tuberculous meningitis is a rare, treatable neurologic disorder, in which early recognition is paramount because outcome depends greatly on the speed with which therapy is initiated. Patients with meningitis and CSF findings of low glucose, elevated protein and pleocytosis with evidence of tuberculosis elsewhere in the body (chest radiographs, positive tuberculin skin test), or a history of exposure to tuberculosis should be treated immediately with antituberculous medication. When the diagnosis remains uncertain, serial examination of the CSF for tuberculous organisms will often yield positive results. The CT scan may show hydrocephalus, a basilar arachnoiditis, or intraparenchymal lesions: tuberculomas. Hydrocephalus may respond to early shunting. Tuberculomas are best treated medically. Therapy should include INH and rifampin; ethambutol and pyrazinamide are suggested for the first 2 months of therapy. Steroids may be useful in diminishing the inflammatory response when altered consciousness or focal neurologic signs are present.
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PMID:CNS tuberculosis. 352 99

A study of 170 patients with juvenile rheumatoid arthritis and a review of the literature indicate that this disease can significantly affect the central nervous system. Signs of CNS dysfunction were observed in 13 children. During the acute toxic stages the EEG is abnormal in many cases. Other manifestations of toxic encephalopathy such as irritability, drowsiness, stupor, convulsions and marked meningismus may be evident in severe cases. Meningitis is often suspected but ruled out by the finding of normal CSF. Steroids can rapidly improve the condition of these children. If ;unexplained' seizures occur during the chronic stage, the diagnosis of cerebral vasculitis should be entertained.
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PMID:Cerebral complications in juvenile rheumatoid arthritis. 466 94

Addition of cortisol and its analogs to soft-agar culture of bone marrow cells markedly decreased the number of monocyte colonies in the presence of colony-stimulating factor. Steroids of other categories and cortisol metabolites were much less inhibitory than cortisol, and the shape of dose-response curve apparently differed between cortisol and other steroids. The action of cortisol was not influenced by excess progesterone or testosterone. Addition of cortisol succinate in liquid cultures of CSF-stimulated cells caused a gradual decrease of cellular uptake of [3H]thymidine. The steroid also suppressed CSF-independent [3H]thymidine uptake, but the time course of suppression obviously differed from that of CSF-dependent uptake. On day 7 of incubation, the steroid-treated cultures contained a smaller number of cells but higher activities of lysosomal enzymes than the control cultures. These results show that the glucocorticoids inhibit proliferation of the cells of monocyte/macrophage lineage.
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PMID:Specificity of the suppressive action of glucocorticoids on the proliferation of monocyte/macrophages in the CSF-stimulated cultures of mouse bone marrow. 660 Oct 26

Granulocyte/macrophage colony-stimulating factor (GM-CSF) is an important hematopoietic growth factor which has been shown to induce proliferation and activation of inflammatory cells, and may play a role in allergic diseases and experimental allergic reactions. Since little is known about the involvement of cytokines in allergic inflammation in the lung, we investigated whether human lung fragments produce GM-CSF in vitro. The present studies demonstrate that human lung fragments produce GM-CSF in vitro and that glucocorticoids are potent inhibitors of this cytokine production. Human lung was cut into fragments, rinsed, and cultured in 60-mm tissue culture plates containing 50 mg of tissue in RPMI 1640 with antibiotics in the presence or absence of a variety of steroids for 18 h. Lung fragments were rinsed and then incubated for an additional 4 h. Supernatants were harvested and analyzed for GM-CSF activity using the GM-CSF/interleukin (IL)-3 responsive M-07e human leukemic cell line. Steroids alone had no effect on M-07e proliferation. Human lung fragments produced 32.1 +/- 11.8 ng of GM-CSF equivalents per gram wet weight of tissue during the 4 h incubation (mean +/- S.E.M., n = 5, range 9.2-74.2). While specific antisera against human GM-CSF neutralized 96.8 +/- 2.8% (n = 5) of the activity, anti-IL-3 antibody had no effect, suggesting most or all of this activity was GM-CSF. Treatment of lung fragments in vitro for 18 h with hydrocortisone (HC) inhibited the production of GM-CSF dose-dependently. Maximal inhibition of GM-CSF production was 72.8 +/- 4.0% at a concentration of 10(-6) M hydrocortisone (n = 5), and the molar concentration of HC that inhibited of GM-CSF production by lung tissue by 50% (IC50) was approximately 4.5 x 10(-7) M. Kinetic studies revealed that a 6 h preincubation with the drug was required for 50% inhibition of GM-CSF production. HC and other glucocorticoids, at a concentration of 0.1 microM, demonstrated significant inhibition of GM-CSF release. Based on the rank order of potency of several glucocorticoids, and the fact that nonglucocorticoid steroids including testosterone and beta-estradiol (0.1 microM) had no effect, we suggest that this is a specific receptor-mediated effect. We conclude that human lung produces GM-CSF in vitro and that antiinflammatory steroids are potent and effective inhibitors of the production of this cytokine. This may contribute to the therapeutic efficacy of these drugs in pulmonary diseases.
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PMID:Antiinflammatory steroids inhibit granulocyte/macrophage colony-stimulating factor production by human lung tissue. 811 12

Contrast-enhanced MRI in patients with MS shows that increased permeability of the blood-brain barrier (BBB) commonly occurs. The changes in capillary permeability often precede T2-weighted MRI evidence of tissue damage. In animal studies, intracerebral injection of the matrix metalloproteinase (MMP) 72-kDa type IV collagenase (gelatinase A) opens the BBB by disrupting the basal lamina around capillaries. Steroids affect production of endogenous MMPs and tissue inhibitors to metalloproteinases (TIMPs). To determine the role of MMP activity in BBB damage during acute exacerbations of MS, we measured MMPs in the CSF of patients with MS. Patients (n = 7) given steroids to treat an acute episode of MS had CSF sampled before and after 3 days of methylprednisolone (1 g/day). Patients had a graded neurologic examination and gadolinium-enhanced MRI before treatment. CSF studies included total protein, cell count, and a demyelinating profile. We measured levels of MMPs, urokinase-type plasminogen activator (uPA), and TIMPs by zymography, reverse zymography, and Western blots. The MMP, 92-kDa type IV collagenase (gelatinase B), fell from 216 +/- 70 before steroids to 54 +/- 26 relative lysis zone units (p < 0.046) after treatment. Similarly, uPA dropped from 3880 +/- 800 to 2655 +/- 353 (p < 0.03). Four patients with gadolinium enhancement on MRI had the most pronounced drop in gelatinase B and uPA. Western immunoblots showed an increase in a complex of gelatinase B and TIMPs after treatment, suggesting an increase in a TIMP (p < 0.05). Reverse zymography of CSF samples showed that steroids increased a TIMP with a molecular weight similar to that of mouse TIMP-3 (p = 0.053). Our results suggest that increased gelatinase B is associated with an open BBB on MRI. Steroids may improve capillary function by reducing activity of gelatinase B and uPA and increasing levels of TIMPs.
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PMID:Effect of steroids on CSF matrix metalloproteinases in multiple sclerosis: relation to blood-brain barrier injury. 864 61

Between 1995 and 2000, 22 cases with low velocity missile injuries of the spine and spinal cord were treated in three service hospitals. All were adult males, with a mean age of 30.7 years. The wounds were caused by splinters in 18 (82%) and bullets in 4 (18%). Twelve patients received more than one splinter. The cervical and thoracic spines were most frequently involved. In 7 cases, there were injuries to other organs. There was extensive initial deficit (quadriplegia, paraplegia) in 18 (82%) cases, while 4 (18%) had partial deficits. The patients were evaluated by spine radiographs. Myelography was done in 4, CT myelography in 11 and MRI in 4 patients. Two patients had intramedullary hematoma without any skeletal injury, and were treated conservatively. Seventeen patients were treated operatively, and associated injuries of other organs received priority management. Surgery was in the form of debridement, exploration of the spinal cord, hemostasis, decompression and dural repair. Steroids and antibiotics were given routinely. Three patients (2 with cervical and 1 with thoracic spine injury) died preoperatively, and 1 (with dorsolumbar injury) died in the postoperative period due to multi-organ injury. Patients with complete injury remained completely paralyzed, while those with an incomplete injury showed improvement in their neurological grades. The initial neurological grade is the best prognostic indicator, and these injuries are often accompanied by multi-organ injuries. There was no instance of postoperative meningitis or CSF leak. These injuries should be explored for debridement and dural repair.
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PMID:Missile injuries of the spine. 1474 34

An autoimmune mechanism for ADEM and MS can be supported by the similar patterns of pathologic changes seen in both diseases with the animal model EAE induced by inoculating animals with nervous tissue and the occurrence of ADEM in patients exposed to nervous tissue during vaccination. Whereas there are no universally agreed-upon criteria for the diagnosis of ADEM, a combination of prodromal illness or preceding vaccination, MRI signs of demyelination, and an acute presentation of neurologic symptoms are the triad most commonly looked for in making the diagnosis of ADEM. An ever-increasing number of infections and vaccinations (nonspecific URIs being most common) has been associated with ADEM. Fever and encephalopathy are seen frequently at presentation. Seizures also are common, as are cranial nerve abnormalities and motor symptoms. A mild pleocytosis or protein elevation is found in the majority of patients with ADEM. Intrathecal IgG synthesis and oligoclonal bands are relatively infrequent but should not be considered inconsistent with the diagnosis of ADEM. White matter changes on T2 in a bilateral although asymmetric distribution with relative sparing of the periventricular region with or without deep gray matter involvement is consistent and to some a requirement for the diagnosis. Low-dose steroids have no beneficial effect in the treatment of ADEM and may be contraindicated. High-dose steroids may have a beneficial effect, particularly in more prolonged illnesses, although the evidence is primarily anecdotal. If steroids are used to improve morbidity, 30 mg/kg/d of methylprednisolone for three to five days is the dose with a six-week taper to reduce the risk of recurrence. The prodromal infection may be a major factor in the ultimate mortality and morbidity of the disease. The current mortality of ADEM is quite low. Whether or not this is an effect of different triggering agents or changes in medical care cannot be determined. In larger series of patients with ADEM, 10% to 20% of children experience some sort of recurrence with the majority occurring in the initial one to two months after the first event. This is sometimes associated with steroid withdrawal. A second group of children have a late second recurrence that clinically may not be MS but a recurrence of ADEM, although longer follow-up may change that assessment. Two months should be allowed before a second relapse is considered a manifestation of MS, whereas a second attack also may occur years after an initial attack of ADEM and still be consistent with ADEM recurrence. MS does occur during childhood, with the youngest children at the least risk, and risk increasing with age. The criteria of Poser et al can be used to diagnose MS in childhood [40]. The presentation of MS in childhood is most often sensory, motor, and brainstem signs and symptoms. A relapsing-remitting course is most common with a first relapse occurring in the year after presentation. MRI findings in MS typically show periventricular changes. Oligoclonal bands and CSF IgG synthesis are found in the majority. Treatments of childhood MS have not been studied adequately, but, when treatments studied in adults are used in children, they are well tolerated. Efficacy has not been shown. The long-term outcome of MS in childhood can be either severe or benign with no clear consensus that childhood MS is either a less or more severe disease than the adult form. ATM and ON treatments and outcomes are particularly difficult to evaluate because of the heterogeneity of populations included in case series and the small numbers reported. Steroids are used with anecdotal reports of their superiority to nontreatment. Outcome in ATM often can be poor, whereas in ON it rarely is. A multinational collaborative effort to study and collect the large numbers necessary to address the important questions in these childhood autoimmune disorders would be of great benefit and the only way likely to demonstrate good evidenced-based medicine practiced in this field.
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PMID:Childhood autoimmune neurologic diseases of the central nervous system. 1474 47


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