PubMed Health⌕ Search

Biomedical subjects

E A Engels

Publications and source records attributed to E A Engels.

At least 19 recordsLinked to original sources
PubMed2003

Multicenter comparison of serologic assays and estimation of human herpesvirus 8 seroprevalence among US blood donors.

BACKGROUND: As part of assessing the possibility of transfusion transmission of human herpesvirus 8 (HHV-8 or Kaposi's sarcoma-associated herpesvirus), HHV-8 seroprevalence was estimated among US blood donors, the performance of HHV-8 serologic tests was compared, and the presence of HHV-8 DNA was tested for in donated blood. STUDY DESIGN AND METHODS: Replicate panels of 1040 plasma specimens prepared from 1000 US blood donors (collected in 1994 and 1995) and 21 Kaposi's sarcoma patients were tested for antibodies to HHV-8 in six laboratories. HHV-8 PCR was performed on blood samples from 138 donors, including all 33 who tested seropositive in at least two laboratories and 22 who tested positive in at least one. RESULTS: The estimated HHV-8 seroprevalence among US blood donors was 3.5 percent (95% CI, 1.2%-9.8%) by a conditional dependence latent-class model, 3.0 percent (95% CI, 2.0%-4.6%) by a conditional independence latent-class model, and 3.3 percent (95% CI, 2.3%-4.6%) by use of a consensus-derived gold standard (specimens positive in two or more laboratories); the conditional dependence model best fit the data. In this model, laboratory specificities ranged from 96.6 to 100 percent. Sensitivities ranged widely, but with overlapping 95 percent CIs. HHV-8 DNA was detected in blood from none of 138 donors evaluated. CONCLUSIONS: Medical and behavioral screening does not eliminate HHV-8-seropositive persons from the US blood donor pool, but no viral DNA was found in donor blood. Further studies of much larger numbers of seropositive individuals will be required to more completely assess the rate of viremia and possibility of HHV-8 transfusion transmission. Current data do not indicate a need to screen US blood donors for HHV-8.

Antibodies, Viral↗
PubMed2001

Cancers associated with Kaposi's sarcoma (KS) in AIDS: a link between KS herpesvirus and immunoblastic lymphoma.

Kaposi's sarcoma (KS), common among persons with acquired immunodeficiency syndrome (AIDS), is caused by KS herpesvirus (KSHV) but whether KSHV causes other malignancies is uncertain. Using linked United States AIDS and cancer registries, we measured the incidence of specific malignancies in persons with AIDS (4-27 months after AIDS onset). We identified associations with KSHV by calculating a relative risk: cancer incidence in persons with KS (all were KSHV-infected) divided by incidence in persons without KS. Using Poisson regression, relative risks were adjusted for human immunodeficiency virus risk group, gender, age, race, and calendar year. We included 189 159 subjects (26 972 with KS). Immunoblastic lymphoma was significantly associated with KS (506 cases; relative risks: unadjusted 2.44, 95%CI 2.00-2.96, adjusted 1.58, 95%CI 1.29-1.93). Only one immunoblastic lymphoma had pleura as primary site. None of 37 other specified malignancies (other non-Hodgkin lymphomas, haematological malignancies, solid tumours) was significantly associated with KS. In summary, the association of immunoblastic lymphoma with KS was specific among examined malignancies and remained significant after statistical adjustment. Our findings, and the previously demonstrated presence of KSHV in the histologically related primary effusion lymphoma, suggest that KSHV is involved in the pathogenesis of some immunoblastic lymphomas.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Thirty-five year mortality following receipt of SV40- contaminated polio vaccine during the neonatal period.

Early poliovirus vaccines, both inactivated and live attenuated, were inadvertently contaminated with simian virus 40 (SV40), a monkey virus known to be oncogenic for newborn hamsters. Although large epidemiologic studies have not identified an elevated cancer risk in persons who received SV40-contaminated vaccines, fragments of SV40 DNA have recently been identified in certain human tumours. We report the follow-up of a cohort of 1073 persons, unique because they received SV40-contaminated poliovirus vaccines as newborns in 1961-63. A previous report of the status of these subjects as of 1977-79 identified 15 deaths, none due to cancer. The present study utilized the National Death Index to identify deaths in the cohort for the years 1979-96. Expected deaths were calculated from Cleveland area sex-, age-, race- and year-specific mortality rates. Increased mortality from all causes was not found. 4 deaths from cancer were found compared to 3.16 expected (P = 0.77). However, 2 deaths from testicular cancer occurred, compared to 0.05 expected (P = 0.002), which may be a chance finding due to multiple comparisons. There were 2 deaths due to leukaemia, a non-significant finding, and no deaths due to tumours of the types putatively associated with SV40. Although these results are, for the most part, consistent with other negative epidemiologic investigations of risks from SV40-contaminated vaccines, further study of testicular cancer may be warranted, and it will be important to continue monitoring this cohort which is now reaching middle-age.

Adult↗
PubMed2001

Cause-specific mortality associated with HIV and HTLV-II infections among injecting drug users in the USA.

BACKGROUND: Human T-lymphotropic virus type II (HTLV-II) is widespread among injecting drug users (IDU) and may contribute to the risk of leukemia/lymphoma, neurodegenerative disease, and perhaps pneumonia, especially with HIV co-infection. METHODS: In 1987--1991, 6570 IDU were tested for HIV and HTLV-II antibodies. In 1998, they were matched to the National Death Index. Numbers of observed deaths of each cause were compared by standardized mortality ratios with the numbers expected, using sex-, race-, age-, and year-specific rates in the general population. Relative risk (RR) associated with each virus, compared to uninfected drug users, was estimated by Poisson modeling. RESULTS: There were 1351 deaths, including 683 (15%) of 4604 participants who enrolled seronegative for both viruses; 328 (47%) of 701 who had HIV but not HTLV-II infection; 220 (21%) of 1033 who had HTLV-II but not HIV infection; and 120 (52%) of 232 who were infected by both viruses. Compared to the general population, mortality for participants with neither virus was increased 4.3-fold [95% confidence interval (CI), 4.0--4.7] and was significantly elevated for virtually every cause of death. With HIV, mortality from medical causes, but not external causes, was increased 3.7-fold (95% CI, 3.3--4.2), particularly with AIDS and related conditions. With HTLV-II, all-cause mortality was reduced (RR, 0.8; 95% CI, 0.7--0.9), with no statistically significant reduction or elevation for any specific cause. A non-significant excess of tuberculosis deaths (RR, 4.6; 95% CI, 0.8--25.2) was noted with HTLV-II, but there was no excess mortality from leukemia/lymphoma, other malignancies, or neurodegenerative disease. CONCLUSIONS: Without HIV or HTLV-II, IDU had profoundly increased mortality from medical and external causes. HIV was specifically associated with death due to AIDS and related conditions. HTLV-II infection was not significantly associated with mortality from any cause, suggesting that it is not a significant human pathogen, even when present with HIV infection.

Cause of Death↗
PubMed2001

Trends in human immunodeficiency virus type 1 (HIV-1) load among HIV-1-infected children with hemophilia.

In human immunodeficiency virus type 1 (HIV-1)-infected persons, virus load (serum/plasma level of HIV) predicts outcome. Virus load trends have been characterized in adults and infants but not in children. Virus load trends in 22 male children with hemophilia who acquired HIV-1 postnatally (age 0.7-5.2 years at seroconversion) were studied. The mean HIV-1 load 2 years after seroconversion was 4.40 log10 copies/mL, and the mean change over time (slope) was 0.03 log10 copies/(mL x year). Significant among-children variation was apparent: a random effects model predicted that 95% of children had early virus loads 3.75-5.04 log10 copies/mL and slopes -0.07 to 0.12 log10 copies/(mL x year). Higher early virus loads and higher slopes were each associated with increased mortality (P=.006 and P=.03, respectively). In conclusion, those subjects had virus load trends similar to those in adults. Early virus loads were lower than those in vertically infected infants, which suggests that factors changing soon after birth affect viral replication.

Adult↗
PubMed2001

Association of cancer with AIDS-related immunosuppression in adults.

CONTEXT: Large-scale studies are needed to determine if cancers other than Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer occur in excess in persons with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). OBJECTIVES: To examine the general cancer pattern among adults with HIV/AIDS and to distinguish immunosuppression-associated cancers from other cancers that may occur in excess among persons with HIV/AIDS. DESIGN, SETTING, AND SUBJECTS: Analysis of linked population-based AIDS and cancer registry data from 11 geographically diverse areas in the United States, including 302 834 adults aged 15 to 69 years with HIV/AIDS. The period of study varied by registry between 1978 and 1996. MAIN OUTCOME MEASURE: Relative risks (RRs) of cancers, calculated by dividing the number of observed cancer cases by the number expected based on contemporaneous population-based incidence rates. We defined cancers potentially influenced by immunosuppression by 3 criteria: (1) elevated overall RR in the period from 60 months before to 27 months after AIDS; (2) elevated RR in the 4- to 27-month post-AIDS period; and (3) increasing trend in RR from before to after AIDS onset. RESULTS: Expected excesses were observed for the AIDS-defining cancers, but non-AIDS-defining cancers also occurred in statistically significant excess (n = 4422; overall RR, 2.7; 95% confidence interval [CI], 2.7-2.8). Of individual cancers, only Hodgkin disease (n = 612; RR, 11.5; 95% CI, 10.6-12.5), particularly of the mixed cellularity (n = 217; RR, 18.3; 95% CI, 15.9-20.9) and lymphocytic depletion (n = 36; RR, 35.3; 95% CI, 24.7-48.8) subtypes; lung cancer (n = 808; RR, 4.5; 95% CI, 4.2-4.8); penile cancer (n = 14; RR, 3.9; 95% CI, 2.1-6.5); soft tissue malignancies (n = 78; RR, 3.3; 95% CI, 2.6-4.1); lip cancer (n = 20; RR, 3.1; 95% CI, 1.9-4.8); and testicular seminoma (n = 115; RR, 2.0; 95% CI, 1.7-2.4) met all 3 criteria for potential association with immunosuppression. CONCLUSION: Although occurring in overall excess, most non-AIDS-defining cancers do not appear to be influenced by the advancing immunosuppression associated with HIV disease progression. Some cancers that met our criteria for potential association with immunosuppression may have occurred in excess in persons with HIV/AIDS because of heavy smoking (lung cancer), frequent exposure to human papillomavirus (penile cancer), or inaccurately recorded cases of Kaposi sarcoma (soft tissue malignancies) in these persons. However, Hodgkin disease, notably of the mixed cellularity and lymphocytic depletion subtypes, and possibly lip cancer and testicular seminoma may be genuinely influenced by immunosuppression.

Adolescent↗
PubMed2001

Risk of T-cell lymphomas in persons with AIDS.

Lymphomas in persons with AIDS are mostly B-cell types, but T-cell lymphomas have also been reported. We examined T-cell lymphoma risk in the 2-year period after AIDS onset by linking 302,834 adults with AIDS to cancer registry data. Of 6,788 cases of non-Hodgkin's lymphoma (NHL) with specified histologies, 96 (1.4%) were T-cell lymphomas. Assessment was based on clinical diagnosis and histology because T-cell marker data were inadequate, but when present, marker data supported the T-cell diagnosis. The relative risk of T-cell lymphoma, estimated by standardized incidence ratio, was 15.0 (95% confidence interval: 10.0--21.7). Risks were increased for all subtypes, including mycosis fungoides, peripheral lymphomas, cutaneous lymphomas, and adult T-cell leukemia/lymphoma (ATLL). HIV-related immunodeficiency could be important, but differences between the population developing AIDS and the general population (e. g., immigration from the Caribbean region for ATLL) might independently increase T-cell lymphoma risk.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Human immunodeficiency virus infection, aging, and cancer.

HIV infection increases non-Hodgkin's lymphoma and Kaposi's sarcoma risk. Among HIV-uninfected persons, risk for these malignancies and others increases with age. As HIV-infected persons age, new patterns in cancer incidence may emerge. In this article, data from the AIDS-Cancer Registry Match study are presented on risk for Kaposi's sarcoma and lung cancer among persons with AIDS. For 132,346 homosexual men with AIDS, Kaposi's sarcoma incidence was highest for men 30-39 years old (5.0 cases/100 person-years) and declined with age (P(trend) <.0001). This trend likely arises from variation in Kaposi's sarcoma herpesvirus prevalence among homosexual men. For 239,257 adults with AIDS (all risk groups), lung cancer incidence increased with age, and was higher than in the general population (P <.0001), probably reflecting heavy smoking among HIV-infected adults. Identifying separate effects of HIV and aging on cancer risk will require detailed data on individuals' HIV infection status and exposures to known carcinogens.

Age Factors↗
PubMed2001

Appendectomy and subsequent risk of inflammatory bowel diseases.

BACKGROUND: Case-control studies have reported an inverse relationship between appendectomy and the risk of ulcerative colitis, but the association has not been confirmed in prospective studies. METHODS: Using national hospital discharge registry data in Denmark, the authors followed up 154,434 patients who underwent appendectomy during the period 1977 to 1989 to investigate whether they had subsequent hospitalizations for ulcerative colitis and Crohn's disease. Ratios of observed-to-expected first hospitalizations for inflammatory bowel diseases served as measures of the relative risk (RR). RESULTS: Hospitalization for ulcerative colitis occurred in 84 patients who had appendectomies versus 97.0 expected (RR = 0.87; 95% CI, 0.69-1.07). RRs were not significantly reduced in subgroups defined by sex, age, time since appendectomy, calendar period, or cause of appendectomy. Hospitalization for Crohn's disease occurred in excess (RR = 2.88; 95% CI, 2.45-3.39; n = 150), notably in the first year after appendectomy (RR = 10.83; 95% CI, 8.49-13.62; n = 73); but after 5 years, the RR was not significantly elevated. CONCLUSIONS: This large population-based cohort study failed to support a significant inverse association between appendectomy and ulcerative colitis risk in the first decade after the operation. The excess of Crohn's disease shortly after appendectomy most likely reflects differential diagnostic problems in patients newly presenting with abdominal pain.

Adult↗
PubMed2001

Strategies for diagnosing and treating suspected acute bacterial sinusitis: a cost-effectiveness analysis.

OBJECTIVE: Symptoms suggestive of acute bacterial sinusitis are common. Available diagnostic and treatment options generate substantial costs with uncertain benefits. We assessed the cost-effectiveness of alternative management strategies to identify the optimal approach. DESIGN: For such patients, we created a Markov model to examine four strategies: 1) no antibiotic treatment; 2) empirical antibiotic treatment; 3) clinical criteria-guided treatment; and 4) radiography-guided treatment. The model simulated a 14-day course of illness, included sinusitis prevalence, antibiotic side effects, sinusitis complications, direct and indirect costs, and symptom severity. Strategies costing less than 50,000 dollars per quality-adjusted life year gained were considered "cost-effective." MEASUREMENTS AND MAIN RESULTS: For mild or moderate disease, basing antibiotic treatment on clinical criteria was cost-effective in clinical settings where sinusitis prevalence is within the range of 15% to 93% or 3% to 63%, respectively. For severe disease, or to prevent sinusitis or antibiotic side effect symptoms, use of clinical criteria was cost-effective in settings with lower prevalence (below 51% or 44%, respectively); empirical antibiotics was cost-effective with higher prevalence. Sinus radiography-guided treatment was never cost-effective for initial treatment. CONCLUSIONS: Use of a simple set of clinical criteria to guide treatment is a cost-effective strategy in most clinical settings. Empirical antibiotics are cost-effective in certain settings; however, their use results in many unnecessary prescriptions. If this resulted in increased antibiotic resistance, costs would substantially rise and efficacy would fall. Newer, expensive antibiotics are of limited value. Additional testing is not cost-effective. Further studies are needed to find an accurate,low-cost diagnostic test for acute bacterial sinusitis.

Acute Disease↗
PubMed2001

[Cancer and HIV].

Explore the source record for details and available documents.

HIV Infections↗
PubMed2000

Latent class analysis of human herpesvirus 8 assay performance and infection prevalence in sub-saharan Africa and Malta.

Human herpesvirus 8 (HHV-8) is thought to be highly prevalent in Mediterranean countries and sub-Saharan Africa, where it causes Kaposi's sarcoma in a small proportion of infected immunocompetent persons. However, the lack of serological tests with established accuracy has hindered our understanding of the prevalence, risk factors and natural history of HHV-8 infection. We tested 837 subjects from Congo, Botswana (mostly young adults) and Malta (elderly adults), using an immunofluorescence assay and 2 enzyme immunoassays (EIAs, to viral proteins K8.1 and orf65). Each assay found HHV-8 seroprevalence to be high (49-87%) in the African populations and generally lower (9-54%) in Malta. However, there was only modest agreement among tests regarding which subjects were seropositive (3-way kappa, 0.05-0.34). We used latent class analysis to model this lack of agreement, estimating each test's sensitivity and specificity and each population's HHV-8 prevalence. Using this approach, the K8.1 EIA had consistently high sensitivity (91-100%) and specificity (92-100%) across populations, suggesting that it might be useful for epidemiological studies. Compared with the K8.1 EIA, both the immunofluorescence assay and the orf65 EIA had more variable sensitivity (80-100% and 58-87%, respectively) and more variable specificity (57-100% and 48-85%, respectively). HHV-8 prevalence was 7% among elderly Maltese adults. Prevalence was much higher (82%) in Congo, consistent with very high Kaposi's sarcoma incidence there. Prevalence was also high in Botswana (87% in Sans, an indigenous group, and 76% in Bantus), though Kaposi's sarcoma is not common, suggesting that additional co-factors besides HHV-8 are needed for development of Kaposi's sarcoma.

Adolescent↗
PubMed2000

Heterogeneity and statistical significance in meta-analysis: an empirical study of 125 meta-analyses.

For meta-analysis, substantial uncertainty remains about the most appropriate statistical methods for combining the results of separate trials. An important issue for meta-analysis is how to incorporate heterogeneity, defined as variation among the results of individual trials beyond that expected from chance, into summary estimates of treatment effect. Another consideration is which 'metric' to use to measure treatment effect; for trials with binary outcomes, there are several possible metrics, including the odds ratio (a relative measure) and risk difference (an absolute measure). To examine empirically how assessment of treatment effect and heterogeneity may differ when different methods are utilized, we studied 125 meta-analyses representative of those performed by clinical investigators. There was no meta-analysis in which the summary risk difference and odds ratio were discrepant to the extent that one indicated significant benefit while the other indicated significant harm. Further, for most meta-analyses, summary odds ratios and risk differences agreed in statistical significance, leading to similar conclusions about whether treatments affected outcome. Heterogeneity was common regardless of whether treatment effects were measured by odds ratios or risk differences. However, risk differences usually displayed more heterogeneity than odds ratios. Random effects estimates, which incorporate heterogeneity, tended to be less precisely estimated than fixed effects estimates. We present two exceptions to these observations, which derive from the weights assigned to individual trial estimates. We discuss the implications of these findings for selection of a metric for meta-analysis and incorporation of heterogeneity into summary estimates. Published in 2000 by John Wiley & Sons, Ltd.

Bias↗
PubMed2000

Identifying human herpesvirus 8 infection: performance characteristics of serologic assays.

Epidemiologic studies of infection with the oncogenic human herpesvirus 8 (HHV-8) depend on serologic methods to diagnose infection. However, optimal strategies for identifying HHV-8 infection remain undefined. We therefore evaluated four enzyme-linked immunoassays (EIAs) and one immunofluorescence assay (IFA) using sera from 87 individuals with the prototype HHV-8 disease, Kaposi's sarcoma (KS), and 210 participants in a hemophilia study (who were presumed not to be infected with HHV-8). Assays performed reasonably well in distinguishing between infected and uninfected persons, with receiver operator curve areas between 0.86 and 0.96. Nonetheless, IFA had only 86% sensitivity and 88% specificity, and no EIA simultaneously had sensitivity and specificity above 90% for any of the optical density (OD) cutpoints used to define seropositivity. Some assays were markedly less sensitive with diluted KS sera, suggesting that they poorly identify low-titer antibodies present in asymptomatic infection. We also developed a classification tree that categorized individuals as seropositive if they had OD > 2.00 on recombinant K8.1 protein EIA or if they had both K8.1 OD between 0.51 and 2.00 and positive IFA results; this strategy had between 80% and 90% sensitivity and 95% and 100% specificity. Overall, assays performed adequately for use in most epidemiologic investigations, but wider applications will require improved tests.

AIDS-Related Opportunistic Infections↗
PubMed2000

Vaccines for preventing typhoid fever.

BACKGROUND: Whole cell vaccines, consisting of relatively crude preparations of Salmonella typhi administered parenterally, are effective but have a high incidence of adverse effects. Two vaccines have been developed more recently. Ty21a (an attenuated strain of S. typhi administered orally) and Vi (the purified bacterial capsule, given parenterally), have appeared less toxic than the older whole cell vaccines and are thought to be equally effective. OBJECTIVES: The objective of this review was to assess the effects of typhoid fever vaccines. SEARCH STRATEGY: We searched the Cochrane Library, Medline, Index Medicus, Embase and reference lists of articles. SELECTION CRITERIA: Randomised trials comparing typhoid vaccines to other types of vaccine or placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Seventeen studies, involving nearly two million people, were included. For the whole cell vaccines single dose regimens provided significant protection for the first two years. Two dose regimens provided significant protection for five years. For the Ty21a vaccine, both two and three dose regimens provided statistically significant protection for two years. The three dose regimen provided protection in the third and fourth years, but protection was not statistically significant in the fifth year. The Vi vaccine provided protection for two years, but the protection in the third year was not significant. The three year cumulative efficacy of two doses of whole cell vaccines was 73% (95% confidence interval 65-80), three doses of Ty21a was 51%, (95% confidence interval 35 to 63) and one dose of Vi was 55% (95% confidence interval 30 to 71). Data on adverse effects were limited, but indicate that whole cell vaccines are more toxic than the newer Ty21a and Vi vaccines. REVIEWER'S CONCLUSIONS: The whole cell vaccines provided more prolonged protection than either the Ty21a vaccine or the Vi vaccine. However whole cell vaccines are associated with higher toxicity.

Adolescent↗
PubMed2000

Meta-analysis of diagnostic tests for acute sinusitis.

To facilitate management of acute sinusitis, we conducted a meta-analysis of published studies comparing diagnostic tests for this disorder. Thirteen studies were identified through literature search. Based on sinus puncture/aspiration (considered most accurate), 49-83% of symptomatic patients had acute sinusitis. Compared with puncture/aspiration, radiography offered moderate ability to diagnose sinusitis (summary receiver operator curve [SROC] area, 0.83). Using sinus opacity or fluid as the criterion for sinusitis, radiography had sensitivity of 0.73 and specificity of 0.80. Studies evaluating ultrasonography revealed substantial variation in test performance. The clinical evaluation, particularly risk scores formally incorporating history and physical examination findings, had moderate ability to identify patients with positive radiographs (SROC area, 0.74). Many studies were of poor quality, with inadequately described test methods and unblinded test interpretation. In conclusion, acute sinusitis is common among symptomatic patients. Radiography and clinical evaluation (especially risk scores) appear to provide useful information for diagnosis of sinusitis.

Acute Disease↗