Biomedical subjects

A E Williams

Publications and source records attributed to A E Williams.

At least 19 recordsLinked to original sources

PubMed1995

Multiple false reactions in viral antibody screening assays after influenza vaccination.

In December 1991, US blood centers reported an unusual increase in donations that tested falsely reactive for antibodies to two or more (multiple false positive) of the following viruses: human immunodeficiency virus type 1 (HIV-1), human T-cell lymphotrophic virus type I (HTLV-I), and hepatitis C virus. Many of these donations were from people who had recently received the 1991-1992 influenza vaccine, raising the possibility that this vaccine had somehow specifically caused the problem of multiple false reactivity. A case-control study of 101 affected donors and 191 matched controls found that recent receipt of any brand of influenza vaccine was significantly associated with testing multiple false positive (p < 0.05), as was a history of recent acute illness (p < 0.05) and of allergies (p < 0.05). Surveillance for monthly rates of multiple reactive donations from May 1990 through December 1992 linked the seasonal cluster of multiple false-positive donations to the use of viral screening test kits thought to react nonspecifically to donor immunoglobulin M. There was no similar increase in multiple false-positive donations during the 1992-1993 influenza vaccination season after the HIV-1 and hepatitis C virus tests were replaced; however, the number of donations that were falsely reactive for only HTLV-I almost doubled, indicating that false reactivity was not specifically associated with the 1991-1992 influenza vaccine. Retesting of affected donors found that the duration of HTLV-I and hepatitis C virus false reactivity was 3-6 months. The cluster of multiple false-positive donations in 1991 was most likely caused by the test kits used, rather than by the influenza vaccine.

Adolescent↗

PubMed1995

Monocyte recruitment into the scrapie-affected brain.

The recruitment of monocytes into the scrapie-affected brain was investigated in female mice reconstituted with male bone marrow, using a Y-chromosome-specific probe and F4/80 immunocytochemistry. Recruitment of monocytes could be demonstrated in six out of eight animals and the number of recruited cells correlated with the severity of vacuolation in most, but not all, animals. The proportion of microglia derived from recruited monocytes varied between individual animals, did not correlate with the increase in cellularity (glia) in affected areas of brain and did not affect the length of incubation period. Thus, it is unlikely that the recruitment of monocytes is a pivotal event in the development of early pathological changes in scrapie. The morphology of recruited cells in scrapie lesions, as revealed by F4/80 immunoreactivity, was indistinguishable from that of activated resident microglia.

Animals↗

PubMed1995

Cutaneous myiasis due to Dermatobia hominis: a report of six cases.

We report six cases of Dermatobia hominis myiasis imported into the U.K. from Belize. With increasing international travel, myiasis may be encountered more frequently in countries in which the parasites are not indigenous. The life-cycle of D. hominis is described, and scanning electron micrographs show the detailed appearance of the larva.

Adolescent↗

PubMed1995

Pharmacokinetic and pharmacodynamic analysis of the actions of D-amphetamine and D-methamphetamine on the dopamine terminal.

To establish whether the actions of D-amphetamine (Amp) and D-methamphetamine (MeAmp) on the striatal dopamine system were equipotent, pharmacokinetic profiles of each drug were applied to an analysis of their respective induced dopamine efflux profiles. Amp or MeAmp (1 and 5 mg/kg i.v.) was administered to chloral hydrate-anesthetized rats; plasma and brain kinetics were then assessed from 5 to 60 min. Dose-dependent increases in Amp and MeAmp plasma levels resulted in proportional increases in striatum levels that were equivalent for both drugs; elimination rates also were similar and were characterized by a first-order decay process. After MeAmp administration, low levels of brain MeAmp metabolites were detected throughout the 1-hr time period; relative to MeAmp, Amp and p-hydroxy-MeAmp levels were less than 10 and 1%, respectively. The drug-induced dopamine efflux profiles in the striatum were characterized by microdialysis; Amp and MeAmp (1, 2.5 and 5 mg/kg i.v.) effected equivalent, dose-dependent increases in extracellular dopamine levels. For both drugs at 5- and 10-min postinjection, increases in drug striatum levels preceded increases in dopamine efflux. In contrast, from the time of the peak dopamine responses observed at 10 to 20 min until the end of the study at 90 min, changes in striatal drug levels were correlated with extracellular dopamine levels; this correlation was similar for both drugs. These results indicate that Amp and MeAmp pharmacokinetics and their subsequent dopamine responses in the striatum are equivalent. The pharmacokinetic analysis can be extended to the interpretation of other comparative studies that assess effects of Amp and MeAmp.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Transfusion-transmitted retrovirus infection.

This article reviews the history, classification, and disease associations of the known human retroviruses and outlines their profound effects on the practice of transfusion medicine. The immunodeficiency viruses, HIV-1 and HIV-2, produce a cytolytic effect on infected lymphocytes, and are the causative agents of AIDS. In contrast are the oncoviruses, including HTLV-I and HTLV-II, which are typically lymphoproliferative and able to induce cellular transformation. Human foamy viruses, more recently recognized as a potential human neuropathogen, resemble the other retroviruses with their complex genome organization and structure.

AIDS Serodiagnosis↗

PubMed1994

Cytokines, prostaglandins and lipocortin-1 are present in the brains of scrapie-infected mice.

The presence of cytokines, prostaglandins and lipocortin-1 was investigated in terminally affected mice in two models of scrapie. There was marked induction of glial interleukin-1 beta, tumour necrosis factor alpha, prostaglandin E2, prostaglandin F2 alpha and lipocortin-1 immunoreactivity in those areas of the brain showing the characteristic vacuolation of scrapie. A comparison of these staining patterns with those of GFAP and F4/80 showed that their expression occurred predominantly in astrocytes. It is possible that cytokines play a significant role in the pathogenesis of neurodegeneration in scrapie.

Animals↗

PubMed1994

Demographic characteristics and prevalence of serologic markers among donors who use the confidential unit exclusion process: the Retrovirus Epidemiology Donor Study.

BACKGROUND: Most blood centers utilize a confidential unit exclusion (CUE) process, intended to reduce the risk of transfusion-associated infectious diseases by allowing high-risk donors confidentially to exclude their blood from use for transfusion. The effectiveness of this method remains controversial. STUDY DESIGN AND METHODS: Confirmatory or supplemental test results for antibodies to human immunodeficiency virus, human T-lymphotropic virus type I, and hepatitis C virus, as well as hepatitis B surface antigen and syphilis and screening test results for antibodies to hepatitis B core (antigen) and alanine aminotransferase levels were obtained for approximately 1.8 million units donated during 1991 and 1992 at five blood centers within the United States. The prevalences of these infectious disease markers in units that the donors confidentially excluded (CUE+) and units that the donors did not exclude (CUE-) were calculated and examined within demographic subgroups. RESULTS: Units that were CUE+ were 8 to 41 times more likely to be seropositive for antibodies to human immunodeficiency virus and hepatitis C virus, hepatitis B surface antigen, and syphilis and three to four times more likely to react for antibody to hepatitis B core (antigen) or to have elevated alanine aminotransferase levels than units that were CUE- (p < 0.001). The positive predictive value of CUE (the percentage of CUE+ units that were confirmed seropositive for any marker) was 3.5 percent, and the sensitivity of CUE (the percentage of confirmed-seropositive units that were CUE+) was 2.3 percent. CONCLUSION: The current CUE process has low sensitivity and apparently low positive predictive value, and in many cases, it appeared that donors misunderstood it. Yet, CUE was not a "random process," as CUE+ units were more likely to be seropositive for any infectious disease marker than CUE- units. This suggests that efforts to improve the CUE system may be warranted. As risk factors for transfusion-transmitted infection become more difficult to identify by history-based screening, however, such efforts may have limited effect.

Adolescent↗

PubMed1994

Evaluation of clinical and laboratory aspects of antibody tests for detection of hepatitis C virus infection in blood donors and recipients from a low-risk population.

BACKGROUND: When the first-generation enzyme immunoassay (EIA) for detection of antibody to hepatitis C virus (anti-HCV) was approved in May 1990, blood banking agencies recommended testing of all components in inventory. In many cases, one or more components from these units had already been transfused. STUDY DESIGN AND METHODS: Donors that reacted in first-generation EIAs and recipients of their components were identified, and anti-HCV test methods (including first-generation EIA, second-generation EIA, and recombinant immunoblot assay [RIBA]) were evaluated. RESULTS: Of 66 donors identified as anti-HCV-positive by first-generation EIA, 17 were positive in second-generation EIA. Of these 17, 9 reacted in RIBA; 6 of these showed evidence of HCV infection in polymerase chain reaction (4) and/or probable transmission of HCV to a transfusion recipient (3). Of the 48 specimens that were positive in first-generation EIA and negative in second-generation EIA, only 1 was positive in RIBA; serum was not available for polymerase chain reaction testing, and there were no living transfusion recipients in whom to assess evidence of transmission of HCV. CONCLUSION: This study documents the low predictive value of EIAs for anti-HCV in a low-prevalence blood donor population and emphasizes the need for additional testing to confirm the specificity of samples that react in the screening tests.

Adolescent↗

PubMed1994

Multiple unconfirmed-reactive screening tests for viral antibodies among blood donors.

BACKGROUND: In December 1991, the United States Food and Drug Administration received reports of blood donations with unconfirmed reactivity on screening tests for antibodies to human immunodeficiency virus, human T-lymphotropic virus type I, and hepatitis C virus (HCV). Of 91 donors with these test results, 57 (63%) reported a recent influenza vaccination. STUDY DESIGN AND METHODS: To determine the extent of unconfirmed reactivity, the time at which it began, and its association or nonassociation with specific manufacturers' tests, a nationwide survey of blood centers was conducted. A case-donation was defined as a blood donation that was repeatedly reactive, but not confirmed positive, on at least two of the three tests from May 1990 through December 1991. RESULTS: Among 14 million donations screened by 110 centers, 582 case-donations were identified. An increase in case-donations was evident in the fall of 1990 (2.8/100,000 donations). In 1991, rates increased from 0.9 per 100,000 donations in the first quarter to 1.3, 3.2, and 19.7 in subsequent quarters. A significantly higher rate of case-donations was observed among donations tested with one of the two available anti-HCV screening tests (8.0 vs. 1.2/100,000 donations; risk ratio = 6.8; 95% CI = 5.4-8.5). CONCLUSION: Although unconfirmed reactivity on multiple screening tests appeared to be seasonal, its documentation prior to the availability of influenza vaccine in 1991 and higher rates among donations tested with one manufacturer's anti-HCV test indicated that test-specific factors were also involved.

Antibodies, Viral↗

PubMed1994

Detection of human immunodeficiency virus type 1 p24 antigen and plasma RNA: relevance to indeterminate serologic tests.

BACKGROUND: Most enzyme immunoassay-reactive specimens producing indeterminate Western blot results belong to individuals who are not infected with human immunodeficiency virus type 1 (HIV-1). However, a small percentage may correspond to early seroconversion or advanced disease, at which stage partial reactivity on Western blot may be observed. STUDY DESIGN AND METHODS: To determine the utility of HIV-1 p24 antigen and cell-free RNA detection for the resolution of Western blot-indeterminate serologic results, several types of enzyme immunoassay-positive, sero-indeterminate specimens were analyzed. Samples were obtained from infected individuals at the time of seroconversion (n = 20), from patients with AIDS (n = 2), as specimens from clinical samples obtained for diagnostic testing (n = 57), from blood donors producing persistent indeterminate results (n = 47), and from random blood donors (n = 72). RESULTS: HIV-1 p24 antigen was detected in 10 of 20 specimens collected from 9 of 12 individuals who seroconverted and in 2 of 2 AIDS patients. HIV-1 plasma RNA was positive in 22 of 22 samples from those 14 individuals. All of 57 diagnostic specimens and 47 samples obtained from persistently indeterminate donors were negative for HIV-1 p24 antigen and plasma HIV-1 RNA. One of 72 blood donor specimens was positive for HIV-1 plasma RNA and had borderline reactivity for p24 antigen. CONCLUSION: The detection of plasma RNA appears to be sensitive and specific; negative test results may be used to identify false-positive serologic reactions. The detection of p24 antigen and plasma RNA can also be used to confirm HIV-1 infection in persons with indeterminate serologic results associated with early seroconversion or late-stage disease.

Blotting, Western↗

PubMed1994

Characterization of the microglial response in murine scrapie.

The nature of the glial and inflammatory cell responses to infection in scrapie-affected brains was studied in terminally-affected mice of five scrapie models. There were marked astrocytic and microglial responses. Microglia showed increased staining of the surface antigens F4/80, leucocyte-common antigen, type 3 complement receptor, and elevated endocytotic and lysosomal activity. In all models, the astrocytic and microglial responses were largely restricted to anatomical regions of the brain showing vacuolation and/or plaque formation and pathological accumulations of PrP. Expression of MHC Class II was patchy and present on microglia in the neuropil of areas with the most intense microglial activation and on occasional perivascular macrophages. This microglial response may represent a modified form of inflammatory response.

Animals↗

PubMed1994

Postnatal psychosis: a patient's experience with comments by the consulting psychiatrist.

The article describes a patient's experience of postnatal psychosis, a form of bipolar mood disorder which presents as the most severe form of psychological disorder suffered in the postnatal period. Accompanying the patient's description are comments from the consulting psychiatrist involved in the case and description of the three forms of postnatal mood change, i.e. the baby blues, postnatal psychosis and postnatal depression. The article is designed to assist in early recognition of postnatal psychosis, appreciation of the patient's altered state of mind, and encouraging acceptance of psychiatric treatment, all of which are essential for good management of postnatal mood disorders.

Anxiety↗

PubMed1993

Human T-lymphotropic virus (HTLV) types I and II infection in sexual contacts and family members of blood donors who are seropositive for HTLV type I or II. American Red Cross HTLV-I/II Collaborative Study Group.

Interviews and laboratory testing were conducted for 168 contacts referred by former blood donors identified as seropositive for antibody to human T-lymphotropic virus type I (HTLV-I) or type II (HTLV-II). Thirty-two (28%) of 114 heterosexual contacts of seropositive donors, including 12 women and 20 men, were found to be antibody positive. None of 40 offspring (except one adult man who reported sexual contact in Puerto Rico) or 14 other (nonspousal) family members were seropositive. Thirty-one of the seropositive contacts were typeable as having either HTLV-I (52%) or HTLV-II (48%). Assessment of couples found that the median duration of the sexual relationship was significantly longer (p = 0.03) for those in which both partners were infected than in discordant pairs. Analysis of risk history data for 22 infected couples revealed that, in three cases, risk factors (Japanese ancestry or sexual contact with an injecting drug user) could be identified in the women, but not in their male partners. Among couples in which the male had the greater risk history, the risk factor was either a history of transfusion, birth or sexual exposure in an endemic area, or injected drug use. Counseling strategies for individuals with HTLV-I or HTLV-II infection should take into account the relatively high seroprevalence in their partners and should address the potential for sexual transmission in both directions.

Adolescent↗

PubMed1993

Changes in intention to donate blood under a hypothetical condition of reduced confidentiality.

Lawsuits related to transfusion-associated human immunodeficiency virus infections have increasingly resulted in requests for the release of confidential information about volunteer blood donors. Concern that loss of confidentiality might change blood donor behavior led to a survey of donors at collection sites within an American Red Cross Blood Services Region. Of the 361 respondents, 50.3 percent (181) indicated reduced intent to provide accurate medical and personal history information under conditions of reduced confidentiality. Ten percent (34) indicated that they were not sure whether they would or would not donate blood in the future under this condition. The results indicate that the possibility of release of donors' medical and personal information may have a negative effect on the safety and adequacy of the nation's volunteer blood supply.

Adult↗

PubMed1992

Methadone maintenance treatment and HIV type 1 seroconversion among injecting drug users.

This study examined whether methadone maintenance treatment decreases drug injection enough to significantly limit HIV-1 transmission among injection drug users (IDU). When HIV-1 seroconversion status among prospectively followed methadone maintenance clients was analyzed by treatment retention, 1/56 (2%) of those who remained continuously in treatment seroconverted while 8/42 (19%) of those whose methadone treatment was interrupted seroconverted. When controlled for length of follow up, the difference in seroconversion rate was not statistically significant. Subjects in continuous treatment had a seroconversion rate of 0.7 per 100 person years (95% Confidence Interval [CI] = 0.1, 5.3) and those with interrupted treatment a rate of 4.3 per 100 person years (95% CI = 2.2, 8.6). Subjects in continuous treatment reported less needle sharing (p less than 0.0002), fewer needle sharing partners (p less than 0.002), fewer sexual partners (p less than 0.03), and were more likely to be women (p less than 0.01). These data indicate the need for larger studies to evaluate both client and drug treatment program characteristics which might concomitantly increase treatment retention and decrease HIV-1 risk.

Adult↗

PubMed1992

Molecular biology of phase-variable lipopolysaccharide biosynthesis by Haemophilus influenzae.

Several chromosomal loci are involved in lipopolysaccharide (LPS) biosynthesis by Haemophilus influenzae. Two of these, lic1 and lic2, contain multiple open-reading frames (ORFs) and include tandem repeats of the tetramer CAAT within and at the 5' end of the coding region of the first ORF in each locus. Variation in the number of repeats of CAAT is involved in the variable expression of LPS epitopes, and genes within these loci are involved in the biosynthesis of these epitopes. lic3 also contains multiple ORFs and the CAAT repeats in the same arrangement as in the other two lic loci. However, in lic3 metabolic functions are encoded by the downstream genes. ORF2 is galE, encoding uridine 5'-diphosphogalactose 4-epimerase, and ORF4 is adk, encoding adenylate kinase. A mutant H. influenzae with a deleted galE gene had an altered LPS when grown on media lacking galactose and was of reduced virulence in infant rats.

Amino Acid Sequence↗

PubMed1992

Immunogenic outer-membrane proteins of Haemophilus influenzae type b in infection.

Outer-membrane proteins (OMPs) from Haemophilus influenzae type b (strain Eagan), grown both in vitro (broth) and in vivo (rat intra-peritoneal), were separated by SDS-PAGE. The major OMPs were present in both growth conditions although the amounts of OMP a and OMP d were reduced in rat-grown organisms. There were strong additional bands in in-vivo-grown organisms at 51 and 92 kDa. Antiserum was raised in rabbits against in-vivo-grown bacteria, and absorbed with lysates of in-vitro-grown bacteria. This serum was used in Western blot analysis of OMPs from in-vitro- and in-vivo-grown cells to identify immunogenic proteins present in infection. These infection-associated OMPs had apparent molecular masses of 43 kDa, 48 kDa, 81 kDa and greater than 200 kDa. Bands of reactivity, of the same molecular mass as some of these, were found on immunoblots when rat and human convalescent sera were used as the source of primary antibody. In particular, a band of 81 kDa was recognized by pooled rat and three human convalescent sera.

Animals↗

PubMed1992

Evaluation of an indirect immunofluorescence assay for confirmation of human immunodeficiency virus type 1 antibody in U.S. blood donor sera.

An indirect immunofluorescence assay (IFA) was evaluated as a confirmatory test for antibody to human immunodeficiency virus type 1 in U.S. blood donor sera previously found to be repeatedly reactive by enzyme immunoassay. IFA results were 100% concordant with a licensed Western blot (immunoblot) for 53 negative and 49 positive samples. Four samples which exhibited antibody to viral proteins from more than one gene, yet were indeterminate by Western blot by the manufacturer's criteria, were also reactive by IFA, whereas 49 additional indeterminate samples were IFA negative.

AIDS Serodiagnosis↗