Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
Add more filters










Database
Language
Publication year range
1.
Anesth Analg ; 118(1): 225-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24247226

ABSTRACT

BACKGROUND: Ropivacaine is a long-acting local anesthetic used for continuous peripheral nerve catheter infusions. Catheters may remain in situ for prolonged time periods. In the present study, patients were enrolled to receive continuous peripheral nerve catheters with measurement of free serum ropivacaine concentrations. METHODS: Peripheral nerve catheters were placed for postoperative pain management in trauma patients and infused with ropivacaine 0.2% or bolused with 0.5%. Blood samples were obtained from each subject on days 0 (preinfusion), 3, 5, 7, 10, and every third day until catheter removal. Serum free ropivacaine concentrations were measured via high-performance liquid chromatography and were compared using the Wilcoxon signed rank test. RESULTS: One hundred thirty-three blood samples were analyzed in 35 patients; all serum free ropivacaine concentrations after infusion initiation (99 samples from 35 subjects) were below 0.34 mg/L (previously determined toxic threshold). The highest concentration achieved in a blood sample was 0.19 mg/L; all other values were <0.09 mg/L. The total amount of drug received during the study ranged from 1146 to 22,320 mg (median of 3722 mg). Catheters remained in situ for a median of 7 days (range: 3-23). From day 0 to 3 (preinfusion), 77% of the study participants had an increase in the serum free-fraction ropivacaine concentrations. The median concentration on day 3 was 0.025 mg/L (95% upper confidence limit for mean: 0.05, range: <0.01-0.19); P < 0.001 compared with preinfusion levels). From day 3 to 5, 68% of the participants had a decrease in the serum free ropivacaine concentrations (median level 0.016 mg/L [95% upper confidence limit for mean: 0.021] P = 0.007 for day 5 compared with day 3). CONCLUSIONS: In this study, free serum ropivacaine concentrations remained well below toxic values despite large amounts of drug administration in combat-wounded patients. The administration of continuous ropivacaine infusions over prolonged time periods, coupled with multiple drug boluses, did not produce toxic or near-toxic serum concentrations.


Subject(s)
Amides/administration & dosage , Amides/blood , Anesthetics, Local/administration & dosage , Anesthetics, Local/blood , Autonomic Nerve Block/methods , Adult , Amides/adverse effects , Anesthetics, Local/adverse effects , Autonomic Nerve Block/adverse effects , Autonomic Nerve Block/instrumentation , Catheters, Indwelling/adverse effects , Female , Humans , Male , Middle Aged , Ropivacaine , Time Factors , Young Adult
2.
Thyroid ; 23(10): 1233-7, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23758055

ABSTRACT

BACKGROUND: As defined by the Dietary Supplement Health and Education Act 1997, such substances as herbs and dietary supplements fall under general Food and Drug Administration supervision but have not been closely regulated to date. We examined the thyroid hormone content in readily available dietary health supplements marketed for "thyroid support." METHODS: Ten commercially available thyroid dietary supplements were purchased. Thyroid supplements were dissolved in 10 mL of acetonitrile and water with 0.1% trifloroacetic acid and analyzed using high-performance liquid chromatography for the presence of both thyroxine (T4) and triiodothyronine (T3) using levothyroxine and liothyronine as a positive controls and standards. RESULTS: The amount of T4 and T3 was measured separately for each supplement sample. Nine out of 10 supplements revealed a detectable amount of T3 (1.3-25.4 µg/tablet) and 5 of 10 contained T4 (5.77-22.9 µg/tablet). Taken at the recommended dose, 5 supplements delivered T3 quantities of greater than 10 µg/day, and 4 delivered T4 quantities ranging from 8.57 to 91.6 µg/day. CONCLUSIONS: The majority of dietary thyroid supplements studied contained clinically relevant amounts of T4 and T3, some of which exceeded common treatment doses for hypothyroidism. These amounts of thyroid hormone, found in easily accessible dietary supplements, potentially expose patients to the risk of alterations in thyroid levels even to the point of developing iatrogenic thyrotoxicosis. The current study results emphasize the importance of patient and provider education regarding the use of dietary supplements and highlight the need for greater regulation of these products, which hold potential danger to public health.


Subject(s)
Consumer Product Safety , Dietary Supplements/analysis , Food Contamination , Thyroid Diseases/prevention & control , Thyroxine/analysis , Triiodothyronine/analysis , Animals , Chromatography, High Pressure Liquid , Dietary Supplements/adverse effects , Dietary Supplements/economics , Dietary Supplements/standards , Electrochemical Techniques , Food Labeling , Humans , Internet/economics , Maryland/epidemiology , Patient Education as Topic , Risk , Thyroid (USP)/chemistry , Thyroid Diseases/diet therapy , Thyroid Gland/chemistry , Thyrotoxicosis/chemically induced , Thyrotoxicosis/epidemiology , Thyrotoxicosis/etiology , Thyroxine/adverse effects , Thyroxine/poisoning , Triiodothyronine/adverse effects , Triiodothyronine/poisoning , United States/epidemiology
3.
Arch Otolaryngol Head Neck Surg ; 137(12): 1228-31, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22183902

ABSTRACT

OBJECTIVE: To investigate the efficacy of various topical applications in opening a clotted tympanostomy tube (TT) using an in vitro model. DESIGN: In vitro clinical trial. INTERVENTIONS: Fresh human blood was allowed to clot in the lumen of TTs. Seven agents were tested: 0.9% saline (control), 1-mg/mL alteplase, 100-U/mL unfractionated heparin, 3% hydrogen peroxide (H(2)O(2)), 3% acetic acid, 5% acetic acid, and a mixture of 3% H(2)O(2) and 3% acetic acid. Each agent was added twice a day for 14 days to TTs that were incubated and humidified to simulate ear canal conditions. The tubes were analyzed with binocular microscopy to determine the status of the obstruction. RESULTS: A total of 16 trials per agent, including a saline control, were performed. The saline control, alteplase, and heparin failed to open any TTs in any of the trials. Compared with the control, H(2)O(2) also was not effective (P = .23). Acetic acid was increasingly effective, with a 3% concentration completely clearing 5 of 16 tubes and a 5% concentration completely clearing 11 of 16 tubes (P = .006). The addition of 3% H(2)O(2) to 3% acetic acid did not significantly increase clearance (P = .21). CONCLUSIONS: Thrombolytic agents and H(2)O(2) were not effective in resolving TTs that were clotted with blood in an in vitro environment simulating the ear canal. Increasing concentrations of acetic acid are increasingly effective in this capacity.


Subject(s)
Fibrinolytic Agents/administration & dosage , Middle Ear Ventilation , Postoperative Complications/drug therapy , Thrombosis/drug therapy , Acetic Acid/administration & dosage , Dose-Response Relationship, Drug , Drug Combinations , Equipment Failure , Heparin/administration & dosage , Hydrogen Peroxide/administration & dosage , In Vitro Techniques , Sodium Chloride/administration & dosage , Tissue Plasminogen Activator/administration & dosage , Treatment Outcome
4.
J Nucl Med Technol ; 37(1): 57-9, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19223430

ABSTRACT

UNLABELLED: Our objective was to compare the stability of Kinevac when reconstituted with sodium chloride injection, USP, 0.9%, versus the manufacturer's recommended sterile water for injection, USP, and to determine the effects on stability of deviating from the manufacturer's recommended methods of product preparation. METHODS: Kinevac was reconstituted with either sterile water or 0.9% sodium chloride. Triplicate high-performance liquid chromatography was performed on each vial of reconstituted sample at time zero and at time zero plus 8 h. The concentration of each sample, as measured by the peak area, was recorded at each time point. The process was repeated over 4 consecutive days. RESULTS: Kinevac reconstituted with sterile water resulted in the recovery of 89.73% of the time zero concentration after 8 h. Kinevac reconstituted with 0.9% sodium chloride resulted in chemical stability of the injection, with 80.05% recovery of the time zero value after 8 h. CONCLUSION: Kinevac is more stable when reconstituted with sterile water than when reconstituted with 0.9% sodium chloride. Kinevac should be reconstituted with sterile water for injection as per the manufacturer's instructions.


Subject(s)
Sincalide/chemistry , Sodium Chloride/chemistry , Chromatography, High Pressure Liquid , Drug Stability , Injections , Water
5.
Infect Immun ; 72(8): 4464-70, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15271904

ABSTRACT

The apical membrane antigen 1 of Plasmodium falciparum is one of the leading candidate antigens being developed as a vaccine to prevent malaria. This merozoite transmembrane protein has an ectodomain that can be divided into three subdomains (D I, D II, and D III). We have previously expressed a major portion of this ectodomain and have shown that it can induce antibodies that prevent merozoite invasion into red blood cells in an in vitro growth and invasion assay. To analyze the antibody responses directed against the individual subdomains, we constructed six different genes that express each of the domains separately (D I, D II, or D III) or in combination with another domain (D I+II, D II+III, or D I+III). These proteins were purified and used to immunize rabbits to raise construct-specific antibodies. We demonstrated that D I+II induced a significant amount of the growth-inhibitory antibodies active in the growth and invasion assay.


Subject(s)
Antibodies, Protozoan/blood , Antigens, Protozoan/chemistry , Antigens, Protozoan/immunology , Membrane Proteins/chemistry , Membrane Proteins/immunology , Plasmodium falciparum/immunology , Plasmodium falciparum/pathogenicity , Protozoan Proteins/chemistry , Protozoan Proteins/immunology , Animals , Antibodies, Protozoan/immunology , Antigens, Protozoan/genetics , Antigens, Protozoan/metabolism , Erythrocytes/parasitology , Escherichia coli/genetics , Escherichia coli/metabolism , Immunization , Malaria Vaccines/administration & dosage , Malaria Vaccines/immunology , Malaria, Falciparum/prevention & control , Membrane Proteins/genetics , Membrane Proteins/metabolism , Plasmodium falciparum/chemistry , Plasmodium falciparum/growth & development , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Rabbits , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Recombinant Proteins/metabolism
6.
Infect Immun ; 70(6): 3101-10, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12011004

ABSTRACT

The apical membrane antigen 1 (AMA1) has emerged as a promising vaccine candidate against malaria. Advanced evaluation of its protective efficacy in humans requires the production of highly purified and correctly folded protein. We describe here a process for the expression, fermentation, refolding, and purification of the recombinant ectodomain of AMA1 (amino acids 83(Gly) to 531(Glu)) of Plasmodium falciparum (3D7) produced in Escherichia coli. A synthetic gene containing an E. coli codon bias was cloned into a modified pET32 plasmid, and the recombinant protein was produced by using a redox-modified E. coli strain, Origami (DE3). A purification process was developed that included Sarkosyl extraction followed by affinity purification on a Ni-nitrilotriacetic acid column. The recombinant AMA1 was refolded in the presence of reduced and oxidized glutathione and further purified by using two ion-exchange chromatographic steps. The final product, designated AMA1/E, was homogeneous, monomeric, and >99% pure and had low endotoxin content and low host cell contamination. Analysis of AMA1/E showed that it had the predicted primary sequence, and tertiary structure analysis confirmed its compact disulfide-bonded nature. Rabbit antibodies made to the protein recognized the native parasite AMA1 and inhibited the growth of the P. falciparum homologous 3D7 clone in an in vitro assay. Reduction-sensitive epitopes on AMA1/E were shown to be necessary for the production of inhibitory anti-AMA1 antibodies. AMA1/E was recognized by a conformation-dependent, growth-inhibitory monoclonal antibody, 4G2dc1. The process described here was successfully scaled up to produce AMA1/E protein under GMP conditions, and the product was found to induce highly inhibitory antibodies in rabbits.


Subject(s)
Antigens, Protozoan/immunology , Membrane Proteins/immunology , Plasmodium falciparum/immunology , Protein Folding , Protozoan Proteins/immunology , Sarcosine/analogs & derivatives , Animals , Antibodies, Protozoan/immunology , Antigens, Protozoan/biosynthesis , Antigens, Protozoan/genetics , Antigens, Protozoan/isolation & purification , Chromatography, Affinity/methods , Chromatography, Ion Exchange/methods , Cysteine , Edetic Acid , Endotoxins , Escherichia coli , Fermentation , Gene Expression , Membrane Proteins/biosynthesis , Membrane Proteins/genetics , Membrane Proteins/isolation & purification , Nickel , Plasmodium falciparum/genetics , Protein Structure, Tertiary , Protozoan Proteins/biosynthesis , Protozoan Proteins/genetics , Protozoan Proteins/isolation & purification , Rabbits , Sucrose
SELECTION OF CITATIONS
SEARCH DETAIL
...