A decaepitope polypeptide primes for multiple CD8+ IFN-gamma and Th lymphocyte responses: evaluation of multiepitope polypeptides as a mode for vaccine delivery.
(73/744)
Proteins are generally regarded as ineffective immunogens for CTL responses. We synthesized a 100-mer decaepitope polypeptide and tested its capacity to induce multiple CD8(+) IFN-gamma and Th lymphocyte (HTL) responses in HLA transgenic mice. Following a single immunization in the absence of adjuvant, significant IFN-gamma in vitro recall responses were detected for all epitopes included in the construct (six A2.1-, three A11-restricted CTL epitopes, and one universal HTL epitope). Immunization with truncated forms of the decaepitope polypeptide was used to demonstrate that optimal immunogenicity was associated with a size of at least 30-40 residues (3-4 epitopes). Solubility analyses of the truncated constructs were used to identify a correlation between immunogenicity for IFN-gamma responses and the propensity of these constructs to form particulate aggregates. Although the decaepitope polypeptide and a pool of epitopes emulsified in IFA elicited similar levels of CD8(+) responses using fresh splenocytes, we found that the decaepitope polypeptide more effectively primed for in vitro recall CD8(+) T cell responses. Finally, immunogenicity comparisons were also made between the decaepitope polypeptide and a corresponding gene encoding the same polypeptide delivered by naked DNA immunization. Although naked DNA immunization induced somewhat greater direct ex vivo and in vitro recall responses 2 wk after a single immunization, only the polypeptide induced significant in vitro recall responses 6 wk following the priming immunization. These studies support further evaluation of multiepitope polypeptide vaccines for induction of CD8(+) IFN-gamma and HTL responses. (+info)
Nationwide epidemic of septicemia caused by contaminated intravenous products: mechanisms of intrinsic contamination.
(74/744)
Between 1 July 1970 and April 1971, in many hospitals in this country, there were outbreaks of nosocomial septicemia caused by Enterobacter cloacae of E. agglomerans (formerly Erwinia, herbicola-lathyri). All of these hospitals used infusion products manufactured by one company, Abbott Laboratories, and all affected patients had onset of septicemia while receiving the company's infusion products. Septicemia was epidemiologically and microbiologically traced to intrinsic contamination of the company's screw-cap closure for infusion bottles which was sealed with a newly introduced elastomer liner. Epidemic organisms were isolated from these closures. Investigations both in the laboratory and in the manufacturing plant into the mechanism of contamination of these products revealed the following. (i) Epidemic strains were present in numerous areas throughout the manufacturing plants. (ii) Viable microorganisms gained access to the interior of screw-cap closures after the autoclave step of production. (iii) Cooling closures actively drew moisture through the thread interstices into the inner-most depths of the closure. (iv) Transfer of contaminants from closures to fluid was easily effected by simple manipulations duplicating normal in-hospital use. (v) The red-rubber liner used in the company's screw-cap closures before the introduction of elastomer contained a broad-spectrum antimicrobial inhibitor. The findings from this epidemic and the associated studies show that the screw-cap closure as it is now designed cannot be considered secure for products that must remain sterile. (+info)
Adverse event associated with methionine loading test: a case report.
(75/744)
The death of a control subject after an oral load of methionine for a study of the possible relationship between homocysteine and Alzheimer's disease is reported. The subject developed postload plasma concentrations of methionine far beyond those reported previously in humans given the usual oral loading dose of methionine (100 mg/kg body wt). Her preload plasma metabolite values rule out known genetic diseases that might predispose one to unusually high methionine concentrations. The most likely explanation for these events is that the subject received a substantial overdose of methionine. The possibility that extremely high methionine concentrations may lead to severe cerebral effects is discussed, and it is recommended that any move to increase the sensitivity of the usual methionine loading test by increasing the dose of methionine either not be undertaken or be taken only with extreme care. (+info)
Indirect spectrophotometric determination of propranolol hydrochloride and piroxicam in pure and pharmaceutical formulations.
(76/744)
Two simple and sensitive indirect spectrophotometric methods for the assay of propranolol hydrochloride (PPH) and piroxicam (PX) in pure and pharmaceutical formulations have been proposed. The methods are based on the oxidation of PPH by a known excess of standard N-bromosuccinimide (NBS) and PX by ceric ammonium sulfate (CAS) in an acidic medium followed by the reaction of excess oxidant with promethazine hydrochloride (PMH) and methdilazine hydrochloride (MDH) to yield red-colored products. The absorbance values decreased linearly with increasing concentration of the drugs. The systems obeyed Beer's law over the concentration ranges of 0.5 - 12.5 and 0.3 - 16.0 microg/ml for PPH, and 0.4 - 7.5 and 0.2 - 10 microg/ml for PX with PMH and MDH, respectively. Molar absorptivity values, as calculated from Beer's law data, were found to be 1.36 x 10(4) and 2.55 x 10(4) l mol(-1) cm(-1) for PPH, and 2.08 x 10(4) and 2.05 x 10(4) l mol(-1) cm(-1) for PX with PMH and MDH, respectively. The common excipients and additives did not interfere with their determinations. The proposed methods have been successfully applied to the determinations of PPH and PX in various dosage forms. The results obtained by the proposed methods compare favorably with those of official methods. (+info)
Large-scale outbreak of infection with Mycobacterium chelonae subsp. abscessus after penicillin injection.
(77/744)
An outbreak of infection with Mycobacterium chelonae subsp. abscessus after the injection of penicillin in 86 patients attending a factory hospital is reported. The bacterium was isolated both from lids and from the soil where the drug was stored. Molecular analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole-cell proteins and plasmids revealed a pattern identical to that of the strains isolated from the wounds. The source of the infections was soil contamination of the vial lids and was caused by improper use and sterilization of penicillin vials. (+info)
An outbreak of neonatal deaths in Brazil associated with contaminated intravenous fluids.
(78/744)
A nursery outbreak of fever and clinical sepsis resulted in the deaths of 36 neonates in Roraima, Brazil. To determine the cause, epidemiologic studies were performed, along with culture and endotoxin analysis of intravenous (iv) fluids. Affected neonates were more likely to have lower birth weight (2.1 vs. 3.2 kg; P<.01), lower APGAR (activity, pulse, grimace, appearance, and respiration) score at 1 (7 vs. 8; P=.1) or 5 min (8 vs. 9; P=.03), lower gestational age (32 vs. 39 weeks; P=.001), or to receive iv medications (20/20 vs. 2/40; P<.0001). Fever occurred only after iv medication administration. Although culture results of unopened iv medications were negative, endotoxin levels of glucose and distilled water for injection were elevated (3.3 and 1.2 U/mL, respectively). Endotoxin-contaminated iv medications were distributed nationally and may have caused other outbreaks of unexplained death. These results highlight the importance of monitoring both pharmaceutical quality and postmarketing surveillance for adverse events. (+info)
Assuring quality and performance of sustained and controlled release parenterals: workshop report.
(79/744)
This is a summary report of the American Association of Pharmaceutical Scientists, the Food and Drug Administration and the United States Pharmacopoeia co-sponsored workshop on "Assuring Quality and Performance of Sustained and Controlled Release Parenterals." Experts from the pharmaceutical industry, the regulatory authorities and academia participated in this workshop to review, discuss and debate formulation, processing and manufacture of sustained and controlled release parenterals and identify critical process parameters and their control. Areas were identified where research is needed in order to understand the performance of these drug delivery systems and to assist in the development of appropriate testing procedures. Recommendations were made for future workshops, meetings and working groups in this area. (+info)
Cisplatin contamination observed on the outside of drug vials.
(80/744)
Exposure to cytotoxic drugs is of great concern today. Special regulations for handling these drugs during preparation and administration have been implemented in most countries. Concern has also been raised as to whether exposure to these drugs can occur due to contaminated drug vials. In this investigation, wipe samples were taken from drug vials used for platinum-containing drugs, e.g. cisplatin and related drugs. The vials were randomly picked from unbroken packages from different manufacturers. The results showed that drug vials may already be contaminated on the outside when delivered from the manufacturer. (+info)