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Biomedical subjects

S J Stevens

Publications and source records attributed to S J Stevens.

At least 19 recordsLinked to original sources

Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients.

Posttransplant lymphoproliferative disease (PTLD) is a frequent and severe Epstein-Barr virus (EBV)-associated complication in transplantation recipients that is caused by iatrogenic suppression of T-cell function. The diagnostic value of weekly EBV DNA load monitoring was investigated in prospectively collected unfractionated whole blood and serum samples of lung transplantation (LTx) recipients with and without PTLD. In PTLD patients, 78% of tested whole blood samples were above the cut-off value of quantitative competitive polymerase chain reaction (Q-PCR) (greater than 2000 EBV DNA copies per mL blood), with the majority of patients having high viral loads before and at PTLD diagnosis. Especially in a primary EBV-infected patient and in patients with conversion of immunosuppressive treatment, rapid increases in peripheral blood EBV DNA load diagnosed and predicted PTLD. In non-PTLD transplantation recipients, only 3.4% of the whole blood samples was above the cut-off value (P <.0001) despite heavy immune suppression and cytomegalovirus (CMV)-related disease. These findings illustrate the clinical importance of frequent EBV DNA load monitoring in LTx recipients. The increased EBV DNA loads in PTLD patients were restricted to the cellular blood compartment, as parallel serum samples were all below cut-off value, which indicates absence of lytic viral replication. EBV(+) cells in PTLD patients have a very short doubling time, which can be as low as 56 hours, thereby creating the need for high screening frequency in high-risk patients. Furthermore, it is shown that EBV and CMV can reactivate independently in LTx recipients and that EBV DNA load monitoring may be useful in discriminating PTLD from rejection.

Adult↗

Toward standardization of Epstein-Barr virus DNA load monitoring: unfractionated whole blood as preferred clinical specimen.

Epstein-Barr virus (EBV) DNA load monitoring in peripheral blood has been shown to be a useful tool for the diagnosis of aberrant EBV infections. In the present study we compared the relative diagnostic values of EBV DNA load monitoring in unfractionated whole blood and simultaneously obtained serum or plasma samples from Burkitt's lymphoma (BL) patients, transplant recipients, human immunodeficiency virus (HIV)-infected individuals, and infectious mononucleosis (IM) patients by a quantitative competitive PCR (Q-PCR). The EBV DNA load in BL patients was mainly situated in the cellular blood compartment (up to 4.5 x 10(6) copies/ml). EBV DNA loads in unfractionated whole blood and parallel serum samples showed no correlation. In transplant recipients, IM patients, and HIV-infected patients, the EBV burden in the circulation was almost exclusively restricted to the cellular blood compartment, because serum or plasma samples from these patients yielded negative results by Q-PCR, despite high viral loads in corresponding whole-blood samples. A 10-fold more sensitive but qualitative BamHI-W-repeat PCR occasionally revealed the presence of EBV at <2,000 copies of EBV DNA per ml of serum. Spiking of 100 copies of EBV DNA in samples with negative Q-PCR results excluded the presence of inhibitory factors in serum or plasma that influenced the Q-PCR result. Serum samples from all populations were often positive for beta-globin DNA, indicating cell damage in vivo or during serum preparation. We conclude that serum is an undesirable clinical specimen for EBV DNA load monitoring because it omits the presence of cell-associated virus and uncontrolled cell lysis may give irreproducible results or overestimation of the DNA load. Unfractionated whole blood is strongly preferred since it combines all blood compartments that may harbor EBV and it best reflects the absolute viral burden in the patient's circulation.

Blood Donors↗

Alcohol as a risk factor for HIV transmission among American Indian and Alaska Native drug users.

Quantitative alcohol interviews conducted as part of the National Institute on Drug Abuse (NIDA) Native American Supplement revealed very high rates of alcohol use among American Indian and Alaska Native active crack and injection drug users (IDUs). Of 147 respondents who completed the alcohol questionnaire, 100& percent had drunk alcohol within the past month, almost 42& percent reported that they drank every day, and 50& percent drank until they were drunk one-half of the time or more. Injection drug users (IDUs) demonstrated the highest frequency and quantity of alcohol use in the past 30 days. A significant positive association was also found between crack and alcohol use in the past 48 hours (c(2)=5.30, p<.05). Finally, those claiming more episodes of using alcohol before or during sex, reported significantly more events of unprotected sexual intercourse. Qualitative data from all four sites corroborated these quantitative findings. Many individuals also reported episodes of blacking out while drinking, and learned later that they had had unprotected sex with complete strangers or individuals they would not otherwise accept as partners. Implications of these findings for HIV/AIDS prevention efforts are addressed.

Adolescent↗

HIV drug and sex risk behaviors among American Indian and Alaska Native drug users: gender and site differences.

Little research has been conducted on HIV drug and sex risk behaviors of American Indians and Alaska Natives who use illicit drugs. Data from studies conducted with other ethnic groups indicates differences in HIV drug and sex risk behaviors of men and women and between drug users from different regions, cities, communities, and intervention sites. This study examines whether these differences in HIV drug and sex risk behaviors also exist for American Indians and Alaska Natives. Results indicate that risk behaviors of American Indians and Alaska Natives do differ like that of other ethnic groups. In particular American Indian and Alaska Native women reported engaging in significantly greater levels of some drug and many sex risk behaviors than men. Significant differences between intervention sites were also found for intensity of use of various drugs and for some HIV drug risk behaviors.

Acquired Immunodeficiency Syndrome↗

Molecular fine-specificity analysis of antibody responses to human cytomegalovirus and design of novel synthetic-peptide-based serodiagnostic assays.

To identify single immunodominant marker proteins which can replace complex virion antigen in serodiagnostic assays, we investigated in detail the molecular fine specificity of antibody responses in different individuals with latent or active human cytomegalovirus (HCMV) infection. An overview of the HCMV proteins recognized by human antibodies was obtained by immunoblotting. For selected immunodominant proteins the epitope fine specificity of the antibody response was determined by a peptide-scanning enzyme-linked immunosorbent assay (ELISA). Epitope clusters were synthesized as combination peptides and were used for further serologic analysis of immunoglobulin M (IgM) and IgG reactivities with panels of sera from different groups of patients in comparison to those with cytomegalovirus (CMV) virion antigen. Several serum samples had significantly higher reactivities with peptides than with the CMV virion antigen. However, individual serum samples occasionally recognized diverse peptide epitopes, stressing the importance of using combinations of peptides in serologic assays. From these studies we were able to define a specific combination of peptides derived from pp52 (UL44) and pp150 (UL32) for the specific and highly sensitive early detection of HCMV IgM, whereas a combination of peptides from pp150 (UL32), gB (UL55), and pp28 (UL99) was selected to give optimal and specific reactivity with HCMV IgG. On the basis of the results obtained with these peptide combinations, new, highly specific serodiagnostic assays were constructed. These assays had sensitivities of 98.9 and 96.4% for IgG and IgM, respectively, in comparison with the results obtained with the "gold standard," the virion antigen-based ELISA. From the results of this study we conclude that specific combinations of highly defined synthetic peptides can replace complex HCMV virion extracts used in current serodiagnostics and may add to further standardization of HCMV serology.

Antibodies, Viral↗

Monitoring of epstein-barr virus DNA load in peripheral blood by quantitative competitive PCR.

A competitive quantitative PCR (Q-PCR) assay combined with simple silica-based DNA extraction was developed for monitoring of Epstein-Barr virus (EBV) DNA load in unfractionated peripheral blood. The Q-PCR is based on competitive coamplification of a highly conserved 213-bp region of the EBNA-1 open reading frame with an internal standard (IS), added in a known concentration. The IS has the same amplicon length and base composition as the wild-type (WT) EBNA-1 amplicon but differs in 23 internally randomized bases. Competitive coamplification yields two PCR products that are quantified by enzyme immunoassay or by electrochemiluminescence detection, with probes specific for the 23 differing internal nucleotides. The Q-PCR has a sensitivity of 10 copies of either WT or IS plasmid DNA. The Q-PCR was validated by quantification of known amounts of plasmid containing the WT EBNA-1 target. Furthermore, we determined EBV genome copy numbers in different cell lines. For EBV quantification in clinical samples, DNA was isolated from lysed whole blood by silica-affinity purification. Forty-six percent of healthy donor peripheral blood samples were positive by Q-PCR. In most of these samples, viral load was less than 2,000 EBV copies/ml of blood. In peripheral blood samples from two AIDS-related non-Hodgkin's lymphoma patients, elevated EBV loads (up to 120,000 copies/ml) were observed, which decreased upon therapy. In Burkitt's lymphoma patients, up to 4,592,000 EBV genome copies/ml of blood were detected. In conclusion, the EBNA-1-based Q-PCR assay provides a reproducible, accurate, and easy method for studying the relationship between EBV load and clinical parameters.

Burkitt Lymphoma↗

HIV/AIDS risks among Native American drug users: key findings from focus group interviews and implications for intervention strategies.

A multisite study funded through the National Institute on Drug Abuse and the Office of Research on Minority Health was conducted in 1996 to determine the HIV/AIDS prevention needs of Native American out-of-treatment drug users. In an effort to recommend directions for HIV/AIDS prevention programming, one component of this study entailed conducting a series of focus groups at each of four sites: Anchorage, Alaska; Denver, Colorado; Flagstaff, Arizona; and Tucson, Arizona. While some site differences were noted, several consistent thematic findings were revealed across all locations. Specifically, focus group members strongly recommended directly involving key members of the Native American community in conducting outreach and intervention activities, involving Native people as the sources of information, and utilizing local and tribally relevant forms of delivering the message. Other consistent themes included getting messages to smaller communities to prevent the potential "annihilation" of tribes, educating youth, and linking alcohol prevention education to HIV/AIDS education. Findings from this study support the idea that future HIV/AIDS prevention programs must take into account subgroup and individual level differences among Native American drug users.

Acquired Immunodeficiency Syndrome↗

HIV sex and drug risk behavior and behavior change in a national sample of injection drug and crack cocaine using women.

This paper describes HIV sex and drug risk behavior and behavior change of injection drug and crack cocaine using women enrolled in a national multi-site Cooperative Agreement program. Baseline data on the 1,403 women who were randomly assigned to a two session intervention that was standardized across sites indicate that sex and drug risk behavior for becoming infected with HIV was considerable. Six-month post intervention follow-up data for the same sample of women show that significant reductions in sex and drug risk behavior were observed for the entire sample of women for the risk variables under study. Significant reductions were also demonstrated for various sub-groups of women enrolled in the study on most of the sex and drug risk variables. Given these findings, it appears that the standard intervention was effective in assisting drug using women reduce their behaviors that put them at risk of becoming infected with HIV. Further research in needed on the development and evaluation of HIV interventions that target specific risk behaviors and various HIV risk behavior profiles of women.

Adult↗

Violence and HIV sexual risk behaviors among female sex partners of male drug users.

OBJECTIVE: Violence and HIV are emerging as interconnected public health hazards among drug users and their families. The purposes of this study are to (1) determine the prevalence of sexual and physical abuse of non-drug-using female sex partners of male drug users, and (2) ascertain the association between such violence and HIV-related risk behaviors. METHODS: From 11/93 to 11/95, 208 female sex partners of injection drug or crack users in Collier County, FL, Tucson, AZ, and Portland, OR, were interviewed as part of a NIDA-funded HIV risk reduction project. Their mean age was 30 years (range 18-54); 21% were White, 6% African American, 7% Native American, and 63% Hispanic. RESULTS: Of the 208 women, 28% reported being sexually molested and 20% raped before age 13; 41% reported being raped at least once in their lifetime. Forty-two percent of the women were physically assaulted by their sex partners; 36% had been threatened with assaulted by their sex partners. Those who were raped or threatened with assault were more likely to have multiple sex partners and engage in unprotected anal sex; there was a trend for women who had been physically assaulted to be more likely to engage in unprotected anal sex. DISCUSSION: Rape, assault and the threat of assault are commonplace in the histories of female sex partners of male drug users. Experiences of violence and threats of violence are associated with heightened risk for the sexual transmission of HIV. Providers of HIV prevention need to understand the sequelae of violence, and design interventions which empower women to protect themselves from sexual transmission of HIV.

Adult↗

Cluster analysis of HIV intervention outcomes among substance-abusing women.

The study described here presents an innovative approach to analyzing intervention outcomes among women substance abusers participating in a national HIV prevention research study funded by the National Institute on Drug Abuse. We used cluster analysis to divide the women in our sample (N=557) into four distinct subgroups predominantly characterized by differences in drug use, injecting risk, sexual behaviors, and drug and sexual risk combined. The four subgroups resulting from this process were primary crack-using women, primary needle-using women, high-frequency needle-using women, and women with multiple drug and sex risk behaviors. Our analysis focuses on changes in self-reported risk behaviors from baseline to 6-month follow-up. In general, the results clearly indicate that the women are heterogeneous; that is, the subgroups exhibit varying patterns of drug use, injecting risk, sexual behavior, and HIV seropositivity. Significant outcomes were found in many areas, indicating positive changes in risk behaviors. The two smaller subgroups of women--high-frequency needle users and those in the multiple-risk behavior subgroup--reported the highest rate of high-risk behaviors and seropositivity but also showed the greatest change at follow-up. A particularly important finding resulting from our analytical approach is that well over half the women in our sample were primary crack users (n=313). This finding is even more significant in light of the fact that the Cooperative Agreement specifically tried to include 70% or more participants who were injectors. Although the rate of HIV seropositivity is not as high for this crack-using subgroup as for the two smaller needle-using subgroups, a greater number of "women who are HIV positive" are in this primary crack-using subgroup than in all the other subgroups. Most of the crack-using women reported that they were not currently injecting drugs and never shared needles, but 10% were seropositive for HIV, suggesting that their risk comes primarily from sexual behaviors. Behaviors in this larger subgroup of women did not change as dramatically as those of women in the smaller subgroups; however, the women did show improvement in areas related to indirect risk (e.g., alcohol and crack use) and in several areas where change is most needed (e.g., trading sex for drugs and using condoms). The results demonstrate a promising alternative approach to analyzing substance abuse and HIV risk behaviors, and they suggest the need for further research on alternative interventions for women with different patterns of risk behaviors.

Community-Institutional Relations↗

Mothers' awareness of HIV and AIDS.

Health visitors in Northamptonshire carried out a survey of mothers attending child health clinics to determine their knowledge and awareness of HIV and Aids. The aim was to ascertain levels of need for further health education for professional health workers and, in turn, their client groups. Susan J Stevens et al describe the results of the survey which revealed widespread lack of knowledge among women of childbearing age.

Community Health Nursing↗

Differentiating the language disorder in dementia from dysphasia--the potential of a screening test.

A considerable amount of information is now available about the way in which senile dementia of the Alzheimer type (SDAT) affects language performance. Speech and language therapists may have the requisite knowledge to work in the field, but they have few assessment materials to facilitate improved differential diagnosis between language breakdown in dementia and dysphasia. This study highlights the differential diagnostic potential of a short screening test with a weighted scoring system. The best discriminatory effect was in the areas of action picture description, verbal description and confrontation naming. Neither age nor sex appears to have a significant effect on results, and re-test results contribute little to the test's discriminatory power in terms of differential diagnosis between the two groups. The possibilities for future test usage and development are discussed.

Aged↗

Differential naming difficulties in elderly dysphasic subjects and subjects with senile dementia of the Alzheimer type.

This paper reports the results of a study in which elderly dysphasic subjects, and elderly subjects with senile dementia of the Alzheimer type (SDAT) were asked to name two representations of familiar objects. These were presented as coloured photographs, and as black and white line drawings. The results show that, although patients with SDAT perform better overall, there is a significant difference in their ability to name drawings compared to photographs. Analysis of the errors made by both subject groups shows significant differences, especially with regard to errors of visual misperception. The implications of these differences are discussed.

Aged↗

Subjective time experience in an intergenerational sample.

The roles chronological age and gender play in subjective time experience were explored in a sample of 294 adult men and women. Subjective time experience (STE: the difference between subjective age and chronological age) was found to vary widely among individuals, with some being "accurate" (SA = CA), and others either "retarded" (SA less than CA) or "advanced" (SA greater than CA). Males were more retarded in STE than females at every point in the lifespan, and patterns of age differences in adulthood differed for the two sexes as well. The results suggest that chronological age may play a key role in transitions in STE, and that chronological age is more significant in the STE of women than in the STE of men.

Adolescent↗