Erythropoietin Concentrations in Cerebrospinal Fluid of Nonhuman Primates and Fetal Sheep following High-Dose Recombinant Erythropoietin

Neonatology ◽  
2004 ◽  
Vol 85 (2) ◽  
pp. 138-144 ◽  
Author(s):  
Sandra E. Juul ◽  
Ronald J. McPherson ◽  
Francis X. Farrell ◽  
Linda Jolliffe ◽  
Dana J. Ness ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Nonhuman Primates ◽  
High Dose ◽  
Recombinant Erythropoietin ◽  
Fetal Sheep

scholarly journals The Effect of Size, Maturation, Global Asphyxia, Cerebral Ischemia, and Therapeutic Hypothermia on the Pharmacokinetics of High-Dose Recombinant Erythropoietin in Fetal Sheep

2020 ◽  
Vol 21 (9) ◽  
pp. 3042 ◽  
Author(s):  
Simerdeep K. Dhillon ◽  
Guido Wassink ◽  
Christopher A. Lear ◽  
Joanne O. Davidson ◽  
Nicholas H.G. Holford ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Therapeutic Hypothermia ◽  
Combined Treatment ◽  
Full Term ◽  
Prolonged Treatment ◽  
High Dose ◽  
Recombinant Erythropoietin ◽  
Fetal Sheep ◽  
Gestation Age ◽  
Near Term

High-dose human recombinant erythropoietin (rEPO) is a promising potential neuroprotective treatment in preterm and full-term neonates with hypoxic-ischemic encephalopathy (HIE). There are limited data on the pharmacokinetics of high-dose rEPO in neonates. We examined the effects of body weight, gestation age, global asphyxia, cerebral ischemia, hypothermia and exogenous rEPO on the pharmacokinetics of high-dose rEPO in fetal sheep. Near-term fetal sheep on gestation day 129 (0.87 gestation) (full term 147 days) received sham-ischemia (n = 5) or cerebral ischemia for 30 min followed by treatment with vehicle (n = 4), rEPO (n = 8) or combined treatment with rEPO and hypothermia (n = 8). Preterm fetal sheep on gestation day 104 (0.7 gestation) received sham-asphyxia (n = 1) or complete umbilical cord occlusion for 25 min followed by i.v. infusion of vehicle (n = 8) or rEPO (n = 27) treatment. rEPO was given as a loading bolus, followed by a prolonged continuous infusion for 66 to 71.5 h in preterm and near-term fetuses. A further group of preterm fetal sheep received repeated bolus injections of rEPO (n = 8). The plasma concentrations of rEPO were best described by a pharmacokinetic model that included first-order and mixed-order elimination with linear maturation of elimination with gestation age. There were no detectable effects of therapeutic hypothermia, cerebral ischemia, global asphyxia or exogenous treatment on rEPO pharmacokinetics. The increase in rEPO elimination with gestation age suggests that to maintain target exposure levels during prolonged treatment, the dose of rEPO may have to be adjusted to match the increase in size and growth. These results are important for designing and understanding future studies of neuroprotection with high-dose rEPO.

scholarly journals 346. Eastern Equine Encephalitis and Use of Intravenous Immunoglobulin Therapy and High-Dose Steroids

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S242-S243
Author(s):  
Sarah I Collens ◽  
Douglas R Wilcox ◽  
Shibani Mukerji ◽  
Farrah J Mateen ◽  
Isaac H Solomon
Keyword(s):  
Cerebrospinal Fluid ◽  
Temporal Lobe ◽  
Standard Of Care ◽  
High Dose ◽  
High Morbidity ◽  
Intravenous Immunoglobulin Therapy ◽  
Eastern Equine Encephalitis ◽  
Neuroanatomical Region ◽  
Ivig Administration

Abstract Background Eastern equine encephalitis (EEE) is a mosquito-borne viral infection with significant neurological morbidity and mortality. The clinical presentation and patient outcomes after treatment with IVIG, high-dose steroids, or standard of care alone in EEE remains unclear. Methods A retrospective observational study of patients admitted to two tertiary academic medical centers in Boston, Massachusetts with EEE from 2005 to 2019. Results Of 17 patients (mean [SD] age, 50 [26] years; 10 (59%) male, and 16 (94%) White race), 17 patients had fever (100%), 15 had encephalopathy (88%), and 12 had headache (71%). Eleven of 14 patients with cerebrospinal fluid (CSF) cell count differential had a neutrophil predominance (mean [SD], 60.6% of white blood cells [22.8]) with an elevated protein level (mean [SD], 112 mg/dL [48.8]). Affected neuroanatomical regions included the basal ganglia (n=9/17), thalamus (n=7/17), and mesial temporal lobe (n=7/17). A total of 11 patients (65%) received IVIG; 8 (47%) received steroids. Of the patients who received IVIG, increased time from hospital admission to IVIG administration correlated with worse long-term disability as assessed by modified Rankin Score (mRS) (r=0.72, p=0.02); steroid use was not associated with mRS score. The mortality was 12%. Figure 1. Imaging Characteristics: Typical Pattern of MRI Involvement and Affected Neuroanatomical Regions in Patients with Eastern Equine Encephalitis. All images displayed are the T2-FLAIR sequence. (A) Representative images of pattern of typical neuroanatomical region involved in one patient with demonstrated involvement of the temporal lobe and pons, temporal lobe and midbrain, and basal gangial by T2-FLAIR hyperintensity (panels left to right). (B) Representative images of patients with mild (mRS 0–2), moderate (mRS 3–4), and severe (mRS 5–6) disability score at discharge. (C) Representative images of one patient over course of hospitalization at days 1, 4, and 10 after admission. (D) Quantification of neuroanatomical region involvement in initial MRI of patients with EEE as determined by T2-FLAIR hyperintensity. An area was scored as abnormal only once per patient. Figure 2. Outcomes in Patients with Eastern Equine Encephalitis. Patient disability by modified Rankin Score (mRS) of EEE patients at admission to the hospital, discharge from the hospital, and last recorded follow-up (A). Time to IVIG administration compared to mRS at discharge (B), and most recent clinical follow-up (C). Table 1. Demographics, Clinical Characteristics, and Laboratory Data in Patients with Eastern Equine Encephalitis. Abbreviations: CSF = cerebrospinal fluid, WBC = white clood count, EEG = electroencephalogram, ALT = alanine aminotransferase, AST = aspartate transaminase. Demographic data was collected for all patients with confirmed EEE. Altered mental status included any description of encephalopathy, confusion, or difficulty with attention. Seizures were defined as clinical events with a high-degree of suspicion to be true seizures, and were entirely comprised of generalized tonic-clonic seizures. Conclusion Clinicians should suspect EEE in immunocompetent patients with early subcortical neuroimaging abnormalities and CSF neutrophilic predominance. This study suggests a lower mortality than previously reported, but a high morbidity rate in EEE. IVIG as an adjunctive to standard of care may be considered early during hospitalization. Disclosures All Authors: No reported disclosures

Cerebrospinal Fluid IgG Changes in Neurosyphilis After High-Dose Penicillin G Treatment

1987 ◽  
Vol 44 (3) ◽  
pp. 249-249 ◽  
Author(s):  
P. Mazzarello ◽  
M. Poloni ◽  
A. Citterio ◽  
C. Camana ◽  
M. Ceroni
Keyword(s):  
Cerebrospinal Fluid ◽  
Penicillin G ◽  
High Dose

Effect of age on cisternal cerebrospinal fluid concentrations of monoamine metabolites in nonhuman primates

1988 ◽  
Vol 13 (3) ◽  
pp. 353-357 ◽  
Author(s):  
Steven E. Shelton ◽  
Ned H. Kalin ◽  
John P. Gluck ◽  
Michael F. Keresztury ◽  
Vicki A. Schneider ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Nonhuman Primates ◽  
Monoamine Metabolites ◽  
Effect Of Age

Plasma and cerebrospinal fluid pharmacokinetics of 9-aminocamptothecin (9-AC), irinotecan (CPT-11), and SN-38 in nonhuman primates

1998 ◽  
Vol 41 (6) ◽  
pp. 464-468 ◽  
Author(s):  
Susan M. Blaney ◽  
Chris Takimoto ◽  
Daryl J. Murry ◽  
Nancy Kuttesch ◽  
Cynthia McCully ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Nonhuman Primates

scholarly journals High-Dosage Cefazolin Achieves Sufficient Cerebrospinal Diffusion To Treat an External Ventricular Drainage-Related Staphylococcus aureus Ventriculitis

2018 ◽  
Vol 63 (2) ◽  
pp. e01844-18 ◽  
Author(s):  
Matthieu Grégoire ◽  
Benjamin Gaborit ◽  
Colin Deschanvres ◽  
Raphaël Lecomte ◽  
Guillaume Deslandes ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cerebrospinal Fluid ◽  
Continuous Infusion ◽  
External Ventricular Drainage ◽  
High Dose ◽  
Ventricular Drainage ◽  
Content Type

ABSTRACT A patient received continuous infusion of cefazolin 10 g then 8 g daily for an external ventricular drainage-related methicillin-susceptible Staphylococcus aureus (MSSA) ventriculitis. Median free concentrations in the cerebrospinal fluid were 11.9 and 6.1 mg/liter after 10- and 8-g doses, respectively. Free concentrations in the cerebrospinal fluid were always above the MIC usually displayed by methicillin-susceptible Staphylococcus aureus (MSSA) isolates. These results support the use of high-dose cefazolin to achieve sufficient meningeal concentrations.

scholarly journals Plasma and Cerebrospinal Fluid Pharmacokinetics of Intravenous Oxaliplatin, Cisplatin, and Carboplatin in Nonhuman Primates

2005 ◽  
Vol 11 (4) ◽  
pp. 1669-1674 ◽  
Author(s):  
Shana S. Jacobs ◽  
Elizabeth Fox ◽  
Christopher Dennie ◽  
Lindsey B. Morgan ◽  
Cynthia L. McCully ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Nonhuman Primates

Sequential combination of systemic high-dose ara-C and asparaginase for the treatment of central nervous system leukemia and lymphoma.

1984 ◽  
Vol 2 (2) ◽  
pp. 98-101 ◽  
Author(s):  
S Amadori ◽  
G Papa ◽  
G Avvisati ◽  
M C Petti ◽  
M Motta ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Potential Role ◽  
High Dose ◽  
Effective Treatment Modality ◽  
Sequential Administration ◽  
Sequential Combination ◽  
Central Nervous System Leukemia ◽  
Meningeal Disease

Eight patients with overt central nervous system (CNS) leukemia and lymphoma were treated with sequential administration of systemic high-dose cytosine arabinoside (HiDAC) and asparaginase (ASP) with no direct CNS therapy. Complete clearing of the cerebrospinal fluid (CSF) was achieved in six (86%) of seven patients with meningeal disease, generally after the first course of therapy. Two patients presented with evidence of extensive intracerebral disease; both responded with a greater than 50% regression of the tumor infiltrates. Concomitant extraneurologic localizations responded equally well to HiDAC/ASP: responses were seen in four of five patients, including complete remission in three of four patients who presented with marrow involvement. Toxicity was generally moderate and limited to myelosuppression (eight of eight patients), tolerable nausea and vomiting (eight of eight patients), mild hepatotoxicity (two of eight patients), and oral mucositis (one of eight patients). These results indicate that HiDAC/ASP is a tolerable and highly effective treatment modality for CNS leukemia and lymphoma and suggest its potential role for sanctuary chemoprophylaxis.

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