An active haemovigilance programme characterizing the safety profile of 7437 platelet transfusions prepared with amotosalen photochemical treatment.

BACKGROUND: An active haemovigilance programme was implemented to survey adverse events (AE) associated with transfusion of platelets photochemically treated with amotosalen and ultraviolet A (PCT-PLT). The results of 5106 transfusions have already been reported. Here we report the results of an additional 7437 PCT-PLT transfusions. METHODS: The focus of this ongoing haemovigilance programme is to document all AEs associated with PCT-PLT transfusion. Data collected for AEs include: time of event after starting transfusion, clinical descriptions, vital signs, results from radiographs and bacterial cultures, event severity (Grade 0-4) and causal relationship to PCT-PLT transfusion. RESULTS: One thousand four hundred patients (mean 60 years, range 1-96) received PCT-PLT transfusions. The majority of the patients (53.4%) had haematology-oncology diseases and required conventional chemotherapy (44.8%) or stem cell transplantation (8.6%). Sixty-eight PCT-PLT transfusions were associated with AE. Acute transfusion reactions (ATR), classified as an AE possibly related, probably related, or related to PCT-PLT transfusions were infrequent (n = 55, 55/7437 = 0.7%) and most were of Grade 1 severity. Thirty-nine patients (39/1400 = 2.8%) experienced one or more ATRs. The most frequently reported signs/symptoms were chills, fever, urticaria, dyspnoea, nausea and vomiting. Five AEs were considered severe (> or = Grade 2); however, no causal relationship to PCT-PLT transfusion was found. Repeated exposure to PCT-PLT did not increase the likelihood of an ATR. No cases of transfusion-related acute lung injury and no deaths due to PCT-PLT transfusions were reported. CONCLUSIONS: Routine transfusion of PCT-PLT is well-tolerated in a wide range of patients. ATRs related to PCT-PLT transfusion were infrequent and most were of mild severity.

Persistent infection of a lymphoma cell line by herpes simplex virus.

The peripheral blood cells from a patient with a B-cell lymphoma were established in long-term tissue culture. Two years after establishment of the cells in culture they were infected with herpes simplex virus type 2 and the productivity and duration of viral persistence investigated. One week after infection the lymphoblastoid cells were productively infected and have remained so for a period of over 3 years. Expression of a viral glycoprotein antigen was evaluated by using a fluorescein-labeled monoclonal anti-herpes simplex virus type 2 antibody and revealed a spectrum of staining reactions grading from a lightly stippled to very intense pattern. Polymerase chain reaction analysis of the infected cells revealed the presence of the herpes simplex virus type 2 DNA polymerase gene in the infected cells that was absent from the uninfected lymphoblastoid cells. These results taken together with the long-term growth characteristics of both the infected and uninfected lymphoblastoid cells suggest that this cell line may be a good model system for studying viral infection, viral replication, viral latency, and clinical application for the isolation of human herpes virus.

Toxicity management in patients receiving low-dose aldesleukin therapy.

OBJECTIVE: To review the pathophysiology and subsequent treatment options for low-dose aldesleukin-induced toxicity when administered via intravenous bolus infusion, continuous intravenous infusion, or subcutaneous injection. BACKGROUND: The adverse events associated with high-dose aldesleukin therapy (600,000 IU per kg i.v. every 8 h for a maximum of 14 doses) are well documented in the literature; however, the adverse event profile of lower doses and alternative administration routes are less well described. An understanding of the adverse event profile associated with these alternative regimens can enhance management of toxicity. DATA SOURCES: English-language clinical studies, abstracts, and review articles pertaining to low-dose intravenous, continuous intravenous infusion, or subcutaneous injection of aldesleukin, as well as aldesleukin-induced adverse events. STUDY SELECTION AND DATA EXTRACTION: Relevant studies were selected that assist with understanding the pathophysiology, clinical management, diagnosis, and management of aldesleukin-induced adverse events. CONCLUSIONS: Aldesleukin therapy initiates a cytokine-mediated proinflammatory process resulting in a toxicity profile that is different from traditional nonbiologic chemotherapeutic agents. The frequency and severity of adverse events associated with aldesleukin administration are dependent upon dose, route, and administration schedule. In addition, most adverse reactions are self-limiting. Alleviation of aldesleukin-induced adverse effects can usually be achieved on an outpatient basis with agents such as antiemetics, antipyretics, and topical creams or lotions, as well as nonmedication interventions. Aggressive and proactive management of aldesleukin associated toxicities can help facilitate completion of therapy.

Isolation of parainfluenza virus type 3 from cerebrospinal fluid associated with aseptic meningitis.

Parainfluenza virus type 3 has been isolated from the cerebral spinal fluid (CSF) from six individuals--four children and two adults--over a 10-year period. All had fever, and four had signs of meningitis. All recovered uneventfully, including one child undergoing chemotherapy for medulloblastoma. The clinical presentation of this child who developed parainfluenza virus type 3 meningitis is described, and the cases of five other individuals with parainfluenza virus type 3 isolated from the CSF are briefly reviewed. The paramyxovirus parainfluenza type 3, in addition to mumps virus, may be considered capable of infecting the central nervous system.

Analysis of the nucleoside moiety of cobalamin and cobalamin analogues using gas chromatography-mass spectrometry.

Existing techniques for identification of cobalamin and cobalamin analogues generally use the intact molecule during characterization with somewhat ambiguous results. In this study a method is described for the identification of the nucleoside in the lower axial ligand of cobalamin and a variety of naturally occurring cobalamin analogues that differ from cobalamin in the base that is present in the nucleoside. Cobalamin and cobalamin analogues were isolated from biological samples by affinity chromatography using R-protein-Sepharose columns. The nucleosides of the lower axial ligand were then hydrolyzed and isolated by column chromatography using a mixed bed column. Nucleosides were oxidized with periodate and reduced with borohydride. After reisolation, the t-butyldimethylsilyl derivatives were prepared and analyzed using gas chromatography/mass spectrometry with selected ion monitoring. A stable isotope internal standard of cobalamin was biosynthetically produced and used to quantitate cobalamin in rabbit kidney. Cobalamin analogues were also shown to be present in rabbit kidney, but they contain the 5,6-dimethylbenzimidazole nucleoside (alpha-ribazole) in the lower axial ligand, indicating that these analogues differ from cobalamin in the corrin ring region of the molecule.

Development, use, and availability of a job exposure matrix based on national occupational hazard survey data.

A job exposure matrix has been developed based on potential exposure data collected during the 1972-1974 National Occupational Hazard Survey (NOHS). The survey sample was representative of all U.S. non-agricultural businesses covered under the Occupational Safety and Health Act of 1970 and employing eight or more employees. Potential worker exposure to all chemical, physical, or biological agents was recorded during the field survey if certain minimum guidelines for exposure were met. The job exposure matrix (JEM) itself is a computerized database that assists the user in determining potential chemical or physical exposures in occupational settings. We describe the structure and possible uses of the job exposure matrix. In one example, potential occupational exposures to elemental lead were grouped by industry and occupation. In a second example, the matrix was used to determine exposure classifications in a hypothetical case-control study. Present availability as well as future enhancements of the job exposure matrix are described.

National estimates of occupational exposure to animal bladder tumorigens.

A prevention program for occupational bladder cancer should be based on an estimate of the number of workers previously and currently exposed to bladder carcinogens. The National Occupational Exposure Survey (NOES), which identified potential occupational exposures in approximately 5000 private sector firms in 1981 to 1983, is the best available source for recent hazard estimates; the National Occupational Hazard Survey (NOHS), conducted in 1972 and 1974, for past exposure estimates. The National Institute for Occupational Safety and Health Registry of Toxic Effects of Chemical Substances (RTECS) identified nearly 200 substances associated with animal bladder tumors. From NOES and NOHS, the numbers of workers with full time (greater than or equal to 4 hours/day) or any potential occupational exposure were estimated for the United States. About 60,000 workers were potentially exposed in the early 1970s and about 700,000 in the early 1980s on a full-time basis to the compounds on the RTECS list also appearing in NOES, and about 1.8 million workers in the 1970s and almost 3.5 million in the 1980s had some occupational exposure. Because matches were not found for many compounds and because NOES covers only part of the US work force, these are probably underestimates. The estimates for the number of exposed workers do not imply that these workers all have increased risk of developing bladder cancer, because some animal tumorigens may not be human carcinogens and our estimates are based on potential rather than measured exposures. The risk would depend on the potency, duration, and intensity of the actual exposures. Nevertheless these estimates are useful in estimating the approximate magnitude of the potential occupational exposure to animal bladder tumorigens.

A G1 glycoprotein epitope of La Crosse virus: a determinant of infection of Aedes triseriatus.

Arthropod-borne viruses (arboviruses) have specific vector-vertebrate host cycles in nature. The molecular basis of restriction of virus replication to a very limited number of vector species is unknown, but the present study suggests that viral attachment proteins are important determinants of vector-virus interactions. The principal vector of La Crosse (LAC) virus is the mosquito Aedes triseriatus, and LAC virus efficiently infects the mosquito when ingested. However, a variant (V22) of LAC virus, which was selected by growing the virus in the presence of a monoclonal antibody, was markedly restricted in its ability to infect Ae. triseriatus when it was ingested. Only 15% of the mosquitoes that ingested V22 became infected and 5% of these developed disseminated infections. In contrast, 89% of the mosquitoes that ingested LAC became infected and 74% developed disseminated infections. When V22 was passed three times in mosquitoes by feeding, a revertant virus, V22M3, was obtained that infected 85% of Ae. triseriatus ingesting this virus. In addition, V22M3 regained the antigenic phenotype and fusion capability of the parent LAC virus. These results suggest that the specificity of LAC virus-vector interactions is markedly influenced by the efficiency of the fusion function of the G1 envelope glycoprotein operating at the midgut level in the arthropod vector.

The prevalence of screening in industry: report from the National Institute for Occupational Safety and Health National Occupational Hazard Survey.

Data from 4,500 workplaces surveyed by the National Institute for Occupational Safety and Health (NIOSH) in the National Occupational Hazard Survey (1972 to 1974) and National Occupational Exposure Survey (1981 to 1983) show an increase in both preplacement and periodic medical screening in US industries during the past decade. The distribution of screening is primarily related to plant size, but also varies considerably by industry type; further, plants with industrial hygiene and safety programs and/or unions are more likely to provide screening examinations than those without, irrespective of plant size. As for workers potentially exposed to selected chemical hazards, the first survey provides no consistent evidence that such workers were more likely to receive exposure-specific tests than other workers. The significance of these findings is discussed in the context of the proposed framework for medical screening practices developed by NIOSH researchers.