Effect Of High-dose Methylprednisolone Research Articles

Changes of Hemostatic Factors in Children with Acute Lymphoblastic Leukemia Receiving Combined Chemotherapy Including High Dose Methylprednisolone and L-Asparaginase

In this study, protein C (PC), protein S (PS), heparin cofactor II (HCFII), prothrombin fragment 1+2 (PF 1,2), thrombin-antithrombin III complex (TAT), von Willebrand factor (vWF) and thrombomodulin (TM) were investigated in 19 patients with acute lymphoblastic leukemia, (ALL) receiving combined chemotherapy including L-asparaginase (L-ASP) and high dose methylprednisolone (HDMP). HDMP was administered in doses of 30 mg/kg/day for 7 days, and 20 mg/kg/day for another 7 days. In order to evaluate the effect of HDMP on the hemostatic system, the 8 patients studied here received HDMP (30 mg/kg/day) therapy for 4 days before the combined chemotherapy. These parameters were also studied in 12 healthy children as a control group. PC levels were normal in the patients while PS levels were decreased both before and after combined chemotherapies. Patients with ALL have laboratory signs of coagulation activation such as PF 1,2, TAT prior to initiation of chemotherapy. With combined chemotherapy, TAT levels were found to be normal while PF1,2 were not. TM levels were found to be increased both before and after therapies whereas HCFII and vWF levels were not different from those of the control group. The short course of HDMP therapy did not prominently influence these hemostatic parameters.These results indicate that both the malignant process and the drugs used in combined chemotherapy cause a decrease in natural inhibitors and an increase in procoagulant activity and endothelial injury. These hemostatic changes may contribute to a thrombotic tendency in the patients with ALL.

Effect of High-Dose Methylprednisolone and G-CSF Treatments on Lymphocyte Subtypes in Neutropenic Children with Acute Lymphoblastic Leukemia: A Pilot Study

Treatment of neutropenia with corticosteroids and hemopoietic growth factors may cause alterations in the immune system. This study investigated and compared the effects of various regimens (HDMP, G-CSF, and G-CSF + HDMP) on total lymphocyte counts and subtypes in neutropenic patients with acute lymphoblastic leukemia. Lymphocyte subtypes were studied just prior to treatment and 1 week later. In the HDMP group, total lymphocyte counts and the numbers ofCD3+, CD4+, CD8+, and CD 19+ lymphocytes and monocytes increased, while the helper/supressor lymphocyte ratio decreased. No significant changes were seen in lymphocyte subtypes in the G-CSF and G-CSF+ HDMP groups, apart from an increase in total lymphocyte numbers. In the control group there was an increase in the number of CD3+ and CD8+ lymphocytes and a decrease in the helper/supressor lymphocyte ratio. These results suggest that HDMP has an inducing, rather than a suppressive effect on all lymphocyte subtypes studied.

High-dose methylprednisolone is an alternative treatment for adults with autoimmune thrombocytopenic purpura refractory to intravenous immunoglobulins and oral corticosteroids.

Eight patients with severe chronic autoimmune thrombocytopenic purpura (AITP) refractory to high-dose intravenous immunoglobulin (IVIgG) and/or oral prednisone were treated with one to three infusions of high-dose methylprednisolone (HDMP) (15 mg/kg/day). The mean platelet count before treatment was 12 +/- 10 x 10(9)/L. HDMP therapy led to a safe platelet count (> 50 x 10(9)/L) after 2-5 days in five patients, and a minimal platelet increase (34 x 10(9)/L) able to stop bleeding in a sixth patient. The effect of HDMP was, however, transient in four of five responders. No side effects were observed, even in the four patients older than 70 years. HDMP thus appears to be a good alternative in emergency situations or prior to surgery for patients with AITP refractory to conventional therapy.

High dose methylprednisolone therapy reduces expression of JE/MCP-1 mRNA and macrophage accumulation in the ischemic rat brain

The effects of glucocorticoid (GC) on ischemic brain remain to be investigated. Since GC modulates immunological system, it also may inhibit macrophage accumulation in the ischemic brain. The GC effect, if any, on macrophages in ischemic brain, may be mediated through modulation of JE/MCP-1 gene, a strong monocyte attractant, which is expressed in the rat brain after ischemia. The purpose of the present study is to elucidate the effect of high dose methylprednisolone (MP) treatment on (1) macrophage infiltration, (2) histopathology of the ischemic lesion, and (3) expression of JE/MCP-1 mRNA, in a focal cerebral ischemia model of the rat. Thirty Wistar rats were used in this study. Focal cerebral ischemia was induced by advancing a nylon monofilament into the internal carotid artery until the origin of the middle cerebral artery (MCA) was occluded. For JE/MCP-1 mRNA study, animals ( n = 9) were randomly injected with MP 75 mg/kg (×3) ( n = 3), 100 mg/kg (×3) ( n = 3), or same volume of saline ( n = 3) and killed 24 h after onset of MCA occlusion. Three animals were used as a normal control, and a section of the liver from one rat was used as an internal control for JE/MCP-1 mRNA. Northern blot analysis was performed using murine JE c-DNA. For the histopathological study, animals ( n = 17) were randomly divided into a MP group (MP 100 mg/kg × 3, n = 9) and a control group (saline treated, n = 8), and killed 72 h after onset of MCA occlusion. Brain sections were evaluated with hematoxylin-eosin for lesion size, neuronal damage, and inflammatory cell infiltration. Our data demonstrated that the expression of JE/MCP-1 mRNA is reduced after MP treatment of 75 g/kg × 3 and 100 mg/kg × 3 to 65.6% and 14.8% of saline treated animals, respectively. Macrophage infiltration was markedly reduced in the ischemic brain of MP group compared to control group (preoptic area: p < 0.001, other areas: p < 0.05). However, no difference was detected in neuronal damage, neurologic score, and lesion size between the two groups. We conclude that MP treatment reduces the expression of JE/MCP-1 mRNA and markedly attenuates macrophage accumulation in the ischemic brain of rat. However, this treatment does not influence lesion size, neuronal damage, or neurologic outcome of the animals.

High-dose methylprednisolone treatment-induced changes in immunological parameters in progressive MS patients.

The effect of High-Dose Methylprednisolone (HD-MP) treatment on Peripheral Blood (PB) and Cerebrospinal Fluid (CSF) immune parameters was investigated in 9 patients with relapsing-progressive Multiple Sclerosis (MS). Short-time effects included reduction of the percentage of CD3+, CD4+ and CD4+CD45RA+ PB lymphocytes and increase in CD3-CD56+ cells. At the end of the treatment, only increase in PB CD19+ and in CSF CD8+, CD8+CD28+ and decrease of CSF CD4+CD45RA- and serum IL2R levels were observed. No changes in CD11a+CD4+, CD18+CD14+ PB cells were observed after treatment. The results further stress the complex and multifaceted action of HD-MP on immune parameters.

The effects of high-dose methylprednisolone on gadolinium-enhanced magnetic resonance imaging and cerebrospinal fluid measurements in multiple sclerosis

Blood-brain barrier (BBB) disruption is probably the first event in the lesion development in multiple sclerosis (MS). This stage can be visualized by gadolinium-enhanced magnetic resonance (MR) imaging of the brain. Serial MR imaging studies have indicated a continuous spectrum of disease activity with waxing and waning of acute lesions, even in clinically stable MS patients. High-dose intravenous methylprednisolone (MP) has a beneficial clinical effect; reduces gadolinium enhancement, indicating improvement of BBB integrity; and, in MS patients, decreases intrathecal immunoglobulin synthesis with reduction of cerebrospinal fluid (CSF) myelin basic protein (MBP). A correlative triad is noted between gadolinium enhancement, clinical improvement, and decrease of CSF MBP following MP treatment, indicating a relationship between restoration BBB integrity, clinical improvement and decrease of myelin breakdown. It is not clear whether MP interferes primarily with the process of demyelination or reacts non-specifically with its mediators.

Chemiluminescence of neutrophils in patients with glomerulonephritis treated with methylprednisolone

The effect of high dose methylprednisolone (Solu-Medrol, Up John) (1000 mg) on chemiluminescence (CL) of peripheral blood neutrophils in patients with various primary glomerulopathies was determined. Contrary to the well-established influence of corticosteroids on in vitro suppression of leukocytic chemiluminescence, our studies disclose a remarkable enhancement of neutrophil chemiluminescent activity in patients receiving pulse methylprednisolone infusion. Subsequent administrations of the drug did not result in any significant change of the analysed parameters. Increased chemiluminescence returned to the pretreatment values within approximately seven days. A possible explanation for the observed phenomenon is discussed.

Effect of high-dose methylprednisolone and U74006F on eicosanoid synthesis after subarachnoid hemorrhage in rats.

Free radicals and lipid peroxidation of membrane fatty acids are thought to play a role in the pathogenesis of arterial vasospasm and the physiopathologic patterns of neuronal damage after subarachnoid hemorrhage. We have evaluated the effects of treatment with either high-dose methylprednisolone every 8 hours or a single dose of U74006F on the temporal profile of ex vivo synthesis of four selected eicosanoids in brain slices after experimental induction of subarachnoid hemorrhage in rats. Prostaglandins D2 and E2, prostacyclin and leukotriene C4 levels were determined by radioimmunoassay after 1-hour incubation of the brain slices. The synthesis of prostaglandin D2 and 6-ketoprostaglandin F1 alpha at 48 hours after subarachnoid hemorrhage was significantly higher when compared to sham-operated animals (p = 0.01); prostaglandin E2 release was significantly enhanced at 6 hours after subarachnoid hemorrhage (p = 0.01). The release of the lipoxygenase metabolite was significantly enhanced at 1, 6, and 48 hours after subarachnoid hemorrhage induction. Both treatment regimens significantly reduced the ex vivo synthesis of prostaglandin D2, prostaglandin E2, and leukotriene C4 at 1, 6, and 48 hours after subarachnoid hemorrhage, whereas the effects on 6-ketoprostaglandin F1 alpha synthesis differed in the two treatment groups. U74006F enhanced the synthesis of prostacyclin metabolite in the early phase after subarachnoid hemorrhage, and high-dose methylprednisolone reduced the increasing synthesis at 48 hours. A strict comparison between the two treatments was not possible because of the different modalities of administration. However, these data suggest that the antioxidant effect of single-dose treatment with U74006F influenced the early and delayed effects on enzymatic lipid peroxidation, whereas the effects of methylprednisolone administration every 8 hours were more significant in the delayed phase.

Effect of Methylprednisolone on Intravascular Coagulation and Edema Formation Induced by Venous Occlusion

Cause and effect relations between Intravascular coagulation and increased vascular endothelial permeability have recently been recognized. The purpose of this study was to investigate the effect of high dose methylprednisolone on tissue edema formation and coagulation in canine legs subjected to venous occlusion. Eight mongrel dogs received 30mg/kg methylprednisolone administration intravenously. Eight additional days received normal saline as controls. Hind leg venous pressure was raised to 75mmHg continuously for 5 hours by a tourniquet around the thigh. Venous blood was sampled before tourniquet inflation, six times during tourniquet inflation, and 60 min after tourniquet ination. The sample blood was used for measurement of Sonoclot coagulation analysis, prothrombin time, and activated partial thromboplastin time. At each time of venous blood sampling, circumferences of 3 points of the distal part of the hind leg were measured to assess edema. Coagulation studies indicated initial hypercoagulability, and later hypocoagulability during venous occlusion in the control group. In the methylprednisolone-treated group, coagulation parameters remained unchanged throughout the study. Percent increases in circumferences as indices of edema formation were significantly less in the methylprednisolone-treated group than in the control group. The results suggest that inhibitory action of methylprednisolone on activation of the coagulation system secondary to venous occlusion may be a key factor in maintaining the integrity of endothelial permeability, resulting in less edema formation.

Effect of High-dose Methylprednisolone on Vasospasm After Subarachnoid Hemorrhage

The effects of high-dose methylprednisolone (MP) on vasospasm following subarachnoid hemorrhage (SAH) were investigated. In a double hemorrhage canine model, administration of high-dose MP (10 mg/kg, every 12 hours) reduced angiographic narrowing of the basilar artery and prevented morphological changes in the arterial wall. In addition, increased platelet aggregation observed from days 4 to 7 in untreated SAH dogs was inhibited by the MP treatment. An in vitro experiment showed that MP inhibited platelet aggregation dose-dependently. High-dose MP had a nonspecific vasodilatory effect on the smooth muscle of the basilar artery. In another SAH model with dysautoregulation of cerebral blood flow (CBF), intravenous MP administration markedly attenuated the decrease in both blood pressure and CBF caused by exsanguination. These results indicate that MP has beneficial effects in normalizing CBF dysautoregulation following SAH. High-dose MP has several advantages for preventing and improving the multiple pathological status in cerebral vasospasm following SAH.

Timing of Corticosteroid Treatment: Effect on Lung Lymph Dynamics in Air Embolism Lung Injury in Awake Sheep

In paired experiments, we studied the effects of high-dose methylprednisolone on the acute pulmonary injury caused by 4 h of venous air embolization in 19 chronically instrumented, unanesthetized sheep with lung lymph fistulas. We compared the effect of methylprednisolone (30 mg/kg intravenous bolus) given before embolization, early (1 H) in the course of embolization, late (3 h) in the course of embolization, or after embolization (at the beginning of the recovery period). We measured pulmonary hemodynamics and lymph dynamics. In six sheep we also fixed lung tissue for semiquantitative histology, and in some we measured leukocyte concentrations in blood and in pulmonary lymph. Methylprednisolone did not significantly affect pulmonary hemodynamics but it largely prevented lung injury when it was given before embolization. It also lessened the degree of lung injury when it was given during embolization, although this effect became less marked as treatment was delayed. Methylprednisolone had no effect on lung injury when given after embolization was completed (4 h). We found fewer leukocytes attached to air emboli and fewer endothelial cell gaps in the lungs of sheep given methylprednisolone as prophylaxis. Leukocyte counts were lower in lung lymph and higher in the circulating blood of methylprednisolone-treated sheep. We conclude that methylprednisolone has a preventive effect on air embolism lung injury, such that its effect is greater when given earlier during the development of injury.

Effects of high-dose methylprednisolone on NA +-K +- atpase and lipid peroxidation after experimental subarachnoid hemorrhage

Delirium is frequently observed in the postoperative and intensive care unit (ICU) population. Due to the multifactorial origin of delirium and according to international guidelines (e.g., American Geriatrics Society; Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption (PADIS) guideline), there are several but no incontestable options for prevention and symptomatic treatment.The purpose of the Baden PRIDe (Prevention and Reduction of Incidence of postoperative Delirium) trial was to determine whether postoperative cognitive dysfunction and delirium could be prevented by the combination of possible preventive agents such as haloperidol and ketamine. In addition, pre- and postoperative levels of the biomarkers cortisol, neuron specific enolase (NSE) and S100β were measured to investigate their dynamics in delirious and non-delirious patients after surgery.The Baden PRIDe Trial was an investigator-initiated, phase IV, two-centre, randomised, placebo-controlled, double-blind clinical trial.Perioperative care.182 adult patients that underwent elective or emergency surgery under general or combined (i.e., general and regional) anaesthesia.Pre-anaesthetic, pharmacologic prevention of postoperative brain dysfunction with haloperidol, ketamine, and the combination of both vs. placebo.Assessment of cognitive performance pre- and postoperatively with the MMSE, the DOS, the Nursing Delirium Screening Scale (Nu-DESC) or the Intensive Care Delirium Screening Checklist (ICDSC) during ICU stay.None of the three study arms – haloperidol, ketamine, or both drugs combined - was significantly superior to placebo for prevention of postoperative brain dysfunction and delirium (P = 0.39). Measured levels of postoperative cortisol were significantly higher in delirious patients. S-100β levels were significantly higher in all postoperative outcome groups (cognitive impairment, delirium, no cognitive decline), whereas postoperative NSE levels declined in all groups.The study results offer no possibility for a novel recommendation for prevention of postoperative cognitive decline including delirium. Perioperative S-100β trajectories in patients with cognitive deterioration suggest affection of glial cells in particular.ClinicalTrials.gov NCT02433041; registered on April 7, 2015.

Experimental subarachnoid hemorrhage: Effects of high-dose methylprednisolone and a lazaroid on the release of eicosanoids

Experimental subarachnoid hemorrhage: Effects of high-dose methylprednisolone and a lazaroid on the release of eicosanoids

Effects of methylprednisolone on acute lung paraquat toxicity in sheep.

Infused into sheep, paraquat causes increased flow of protein-rich lung lymph, increased prostanoid production, and neutrophil accumulation in the lung. The effects of high-dose methylprednisolone on the response to paraquat infusion were studied in awake sheep with chronic lung lymph fistulas. Seven sheep were infused with paraquat (30 mg/kg) alone. Six sheep received methylprednisolone (1.0 g plus 0.5 g/h intravenously), beginning 30 min before paraquat (pretreatment), and 5 received methylprednisolone, beginning 4 h after paraquat (post-treatment). Neutrophil accumulation in the lung was measured in biopsy tissue taken at baseline and at postmortem. Methylprednisolone pretreatment significantly prevented the increase in lung lymph flow (paraquat, from 4.4 +/- 0.3 to 11.1 +/- 0.8 ml/h, p less than 0.05; pretreatment, from 4.8 +/- 0.9 to 3.7 +/- 0.3, NS), and the increase in lymph-to-plasma protein concentration ratio (paraquat, from 0.69 +/- 0.02 to 0.80 +/- 0.02, p less than 0.05; pretreatment, from 0.66 +/- 0.06 to 0.60 +/- 0.02, NS) during 8 h after paraquat infusion. Treatment with methylprednisolone after paraquat also reduced the changes in lung lymph flow and protein clearance. Methylprednisolone prior to paraquat significantly inhibited accumulation of 6-keto-PGF1 alpha in lymph and plasma, but did not significantly inhibit accumulation of TxB2 in lymph or plasma. The number of neutrophils in the paraquat lungs was 3 to 4 times that in the control lungs, with or without methylprednisolone. Methylprednisolone pretreatment prolonged the survival time, but did not prevent death within 48 h after paraquat infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Preliminary report: effects of high dose methylprednisolone on delayed cerebral ischemia in patients at high risk for vasospasm after aneurysmal subarachnoid hemorrhage.

Mounting evidence suggests that chronic cerebral vasospasm may be linked to the inflammatory response that follows subarachnoid hemorrhage. Twenty-one patients judged to be at high risk for vasospasm because of either poor admitting grade or a large amount of subarachnoid blood shown by computed tomography were treated with a course of high dose methylprednisolone, and management results were compared to those of a cohort of contemporary control patients matched for grade, number of hemorrhages, time from hemorrhage to admission, time from hemorrhage to operation, aneurysm location, age, and sex. Patients treated with high dose methylprednisolone were twice as likely to have an excellent result and half as likely to die as those who were not treated. The incidence and severity of delayed cerebral ischemia were reduced in treated patients when compared to control patients. None of the treated patients developed a serious side effect that could be attributed to steroid treatment. These findings are consistent with the conclusion that chronic vasospasm is an inflammatory vasculopathy and suggest that early treatment with high dose methylprednisolone may benefit this high risk group of patients.

Effects of methylprednisolone on cortical neural activity, blood flow, and water content in air exposure-induced cerebral edema

The correlation of changes in cortical neuron activity with water content and local cerebral blood flow was investigated in cats with brain edema produced by air exposure. The further effect of high-dose methylprednisolone on these factors was studied. Six hours after exposure of the brain surface to air, the water content of the white matter significantly increased. The local blood flow of the cortex and white matter significantly decreased with significant suppression of cortical neural activity (direct cortical response), indicating that ischemia was responsible for neural suppression. A single, large dose of methylprednisolone (30 mg/kg, i.v.) at the beginning of air exposure significantly reduced brain edema of the cortex and white matter 12 h after air exposure and improved the local blood flow of the cortex. Methylprednisolone also caused a remarkable improvement in cortical neural activity. This steroid effect on cortical neural function may play a role in the rapid neurologic improvement observed with their use in addition to the effect on brain edema.

The effects of high dose methylprednisolone or fluid volume expansion on cerebral haemodynamics and oxygen uptake in endotoxic shock. An experimental study in dogs.

E coli endotoxin has been shown to decrease cerebral blood flow (CBF) and increase cerebral metabolic rate of oxygen (CMRO2) in normocapnic dogs. The aim of this study was to investigate the effects of different clinical treatments on the cerebral and central circulation already under the influence of endotoxin. Thus the animals were treated with either methylprednisolone or a lactated Ringer's solution. CBF, CMRO2 and intracranial pressure were followed. Central haemodynamic parameters, i.e. cardiac output, aortic pressure and pulmonary artery pressure, were also measured. Five dogs were given methylprednisolone (Solu-Medrol) 30 mg/kg 90 min after the endotoxin injection. Following this drug there were no significant changes in CBF when compared to controls. The primarily increased CMRO2 did, however, show a transient decrease. Five animals were treated with a lactated Ringer's solution. (Ringerdex), 30 mg/kg, given intravenously over 20 min starting 90 min after the endotoxin injection. In these animals, the cardiac output as well as CMRO2 returned to the values before endotoxin. CBF did not increase significantly.

Effects of endotoxin on cerebral blood flow in the monkey.

ARTICLESEffects of endotoxin on cerebral blood flow in the monkeyDE WeinerDE WeinerPublished Online:01 Jan 1970https://doi.org/10.1152/ajplegacy.1970.218.1.160MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByLipoteichoic acid, a cell wall component of Gram-positive bacteria, induces sleep and fever and suppresses feedingBrain, Behavior, and Immunity, Vol. 4The Encephalopathy in SepsisCritical Care Clinics, Vol. 24, No. 1The Effect of S. Pneumoniae Bacteremia on Cerebral Blood Flow Autoregulation in Rats13 June 2007 | Journal of Cerebral Blood Flow & Metabolism, Vol. 28, No. 1Extracerebral organ dysfunction and neurologic outcome after aneurysmal subarachnoid hemorrhageCritical Care Medicine, Vol. 27, No. 3Cerebral blood flow during experimental endotoxemia in volunteersCritical Care Medicine, Vol. 25, No. 10Dobutamine increases cerebral blood flow velocity and jugular bulb hemoglobin saturation in septic patientsCritical Care Medicine, Vol. 25, No. 3Changes in Cerebral Blood Flow After Endotoxin in Humans and SheepThe Cell, the Mitochondrion, Oxygen and SepsisLactic acidosis in sepsis: a commentaryIntensive Care Medicine, Vol. 22, No. 1Effects of dobutamine and prostacyclin on cerebral blood flow velocity in septic patientsJournal of Critical Care, Vol. 9, No. 1Sepsis and Cellular MetabolismPeripheral Macro- and MicrocirculationNeurologic Abnormalities in SepsisCerebral Blood Flow and Oxygen Uptake in Endotoxic Shock. An Experimental Study in DogsActa Anaesthesiologica Scandinavica, Vol. 26, No. 3The Effects of High Dose Methylprednisolone or Fluid Volume Expansion on Cerebral Haemo-dynamics and Oxygen Uptake in Endotoxic Shock. An Experimental Study in DogsActa Anaesthesiologica Scandinavica, Vol. 26, No. 3Literature29 January 2009 | Acta Neurologica Scandinavica, Vol. 50, No. S57 More from this issue > Volume 218Issue 1January 1970Pages 160-164 Copyright & PermissionsCopyright © 1970 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1970.218.1.160PubMed4982909History Published online 1 January 1970 Published in print 1 January 1970 Metrics