Bias in Observed Assessments in Medical Education: A Scoping Review.

PURPOSE: Observed assessments are integral to medical education but may be biased against structurally marginalized communities. Current understanding of assessment bias is limited because studies have focused on single specialties, levels of training, or social identity characteristics (SIDCs). This scoping review maps studies investigating bias in observed assessments in medical education arising from trainees' observable SIDCs at different medical training levels, with consideration of medical specialties, assessment environments, and assessment tools. METHOD: MEDLINE, Embase, ERIC, PsycINFO, Scopus, Web of Science Core Collection, and Cochrane Library were searched for articles published between January 1, 2008, and March 15, 2023, on assessment bias related to 6 observable SIDCs: gender (binary), gender nonconformance, race and ethnicity, religious expression, visible disability, and age. Two authors reviewed the articles, with conflicts resolved by consensus or a third reviewer. Results were interpreted through group review and informed by consultation with experts and stakeholders. RESULTS: Sixty-six of 2,920 articles (2.3%) were included. These studies most frequently investigated graduate medical education (44 [66.7%]), used quantitative methods (52 [78.8%]), and explored gender bias (63 [95.5%]). No studies investigated gender nonconformance, religious expression, or visible disability. One evaluated intersectionality, with SIDCs described inconsistently. General surgery (16 [24.2%]) and internal medicine (12 [18.2%]) were the most studied specialties. Simulated environments (37 [56.0%]) were studied more frequently than clinical environments (29 [43.9%]). Bias favoring men was found more in assessments of intraoperative autonomy (5 of 9 [55.6%]), whereas clinical examination bias often favored women (15 of 19 [78.9%]). When race and ethnicity bias was identified, it consistently favored White students. CONCLUSIONS: This review mapped studies of gender, race, and ethnicity bias in the medical education assessment literature, finding limited studies on other SIDCs and intersectionality. These findings will guide future research by highlighting the importance of consistent terminology, unexplored SIDCs, and intersectionality.

Long-Term Antibody Response to SARS-CoV-2 in Children.

Almost 2 years into the pandemic and with vaccination of children significantly lagging behind adults, long-term pediatric humoral immune responses to SARS-CoV-2 are understudied. The C19.CHILD Hamburg (COVID-19 Child Health Investigation of Latent Disease) Study is a prospective cohort study designed to identify and follow up children and their household contacts infected in the early 2020 first wave of SARS-CoV-2. We screened 6113 children < 18 years by nasopharyngeal swab-PCR in a low-incidence setting after general lockdown, from May 11 to June 30, 2020. A total of 4657 participants underwent antibody testing. Positive tests were followed up by repeated PCR and serological testing of all household contacts over 6 months. In total, the study identified 67 seropositive children (1.44%); the median time after infection at first presentation was 83 days post-symptom onset (PSO). Follow-up of household contacts showed less than 100% seroprevalence in most families, with higher seroprevalence in families with adult index cases compared to pediatric index cases (OR 1.79, P = 0.047). Most importantly, children showed sustained seroconversion up to 9 months PSO, and serum antibody concentrations persistently surpassed adult levels (ratio serum IgG spike children vs. adults 90 days PSO 1.75, P < 0.001; 180 days 1.38, P = 0.01; 270 days 1.54, P = 0.001). In a low-incidence setting, SARS-CoV-2 infection and humoral immune response present distinct patterns in children including higher antibody levels, and lower seroprevalence in families with pediatric index cases. Children show long-term SARS-CoV-2 antibody responses. These findings are relevant to novel variants with increased disease burden in children, as well as for the planning of age-appropriate vaccination strategies.

Pessimistic health and optimistic wealth distributions perceptions in Germany and the UK: evidence from an online-survey.

BACKGROUND: Inequalities in health and wealth distributions are becoming pressing societal problems in many countries. How these inequalities are perceived and to what degree perceptions are aligned with actual distributions, is important for trust in public health services, social and economic policies, and policymakers. This study aims to assess perceived and desired levels of inequality in health and wealth in Germany and the UK. METHODS: The online-survey was filled out by 769 volunteers (322 from Germany, 447 from the UK), recruited from an existing commercial panel (Prolific Academic) or via Facebook advertisements in 2019. Perceived and ideal national health and wealth distributions were assessed and compared to actual health indicators (i.e. days absent from work, number of visits to general practitioners (GPs) and self-rated health), and actual wealth distributions with t-tests. RESULTS: A pronounced gap emerged between the estimated, ideal and actual inequality. Both samples strikingly underestimated the proportion of (very) good health in the national distribution by a factor of ~ 2.3 (participants estimated that 34% of the German and 36% of the UK population respectively are very healthy or healthy, while the actual proportion in the population was 75% in Germany and 84% in the UK, P < 0.001 for all). Moreover, actual health distributions were much closer to the desired than the perceived health distributions (78% of German and 72% of UK participants ideally being very healthy or healthy). A reversed pattern of results emerged for wealth in both samples, with wealth inequality being strikingly worse than desired and inequality being underestimated by a factor ~ 1.7 (P < 0.001 for all). Results were consistent across demographic groups. CONCLUSIONS: Respondents in both Germany and the UK have profoundly negative misperceptions regarding the distribution of health, which contrasts with starkly positive misperceptions regarding the distribution of wealth, indicating that the public is healthier but poorer than they think. More importantly, from a public health perspective, a high level of consensus emerged, with both healthy and wealthy participants misperceiving health and wealth distributions.

Lack of reassurance after unexpected positive health risk feedback - an analysis of temporal dynamics.

INTRODUCTION: How do people receive unexpected positive health risk information? While common motivational accounts predict acceptance, consistency accounts such as the cue-adaptive reasoning account (CARA) predict a 'lack of reassurance'. OBJECTIVES: We therefore tested (1) whether people prefer striving for positivity or retaining a sense of self-consistency ('lack of reassurance'), and (2) if there are systematic differences in short- and long-term reception, which would indicate temporal dynamics in processing. METHODS: As part of a longitudinal cohort study, participants of a community health screening (N = 1,055) received their actual cholesterol readings. Feedback reception was assessed immediately, at one month and six months. RESULTS: Processing trajectories for unexpected positive feedback showed a significant 'lack of reassurance' effect over time compared with expected positive feedback, while unexpected negative feedback was less threatening than expected negative feedback. CONCLUSIONS: The perseverance of this 'lack of reassurance' over time indicates that striving for consistency in self-views is a robust phenomenon, even if it means forfeiting a better view of one's own health.

Dynamic Risk Perceptions in Times of Avian and Seasonal Influenza Epidemics: A Repeated Cross-Sectional Design.

Infectious diseases pose a serious threat to humans. Therefore, it is crucial to understand how accurately people perceive these risks. However, accuracy can be operationalized differently depending on the standard of comparison. The present study investigated accuracy in risk perceptions for three infectious diseases (avian influenza, seasonal influenza, common cold) using three different standards for accuracy: Social comparison (self vs. others' risk perceptions), general problem level (risk perceptions for diseases with varying threat levels), and dynamic problem level (risk perceptions during epidemics/seasons vs. nonepidemic/off-season times). Four online surveys were conducted using a repeated cross-sectional design. Two surveys were conducted during epidemics/seasons of avian influenza, seasonal influenza, and common cold in 2006 (n = 387) and 2016 (n = 370) and two surveys during nonepidemic/off-season times for the three diseases in 2009 (n = 792) during a swine flu outbreak and in 2018 (n = 422) during no outbreak of zoonotic influenza. While on average participants felt less at risk than others, indicating an optimistic bias, risk perceptions matched the magnitude of risk associated with the three infectious diseases. Importantly, a significant three-way interaction indicated dynamic accuracy in risk perceptions: Participants felt more at risk for seasonal influenza and common cold during influenza and cold seasons, compared with off-season times. However, these dynamic increases were more pronounced in the perceived risk for others than for oneself (optimistic bias). The results emphasize the importance of using multiple approaches to assess accuracy of risk perception as they provided different information on how accurately people gauge their risk when facing infectious diseases.

Tetrahydroquinolinyl phosphinamidates and phosphonamidates enhancing tolerance towards drought stress in crops via interaction with ABA receptor proteins.

New phosphorous-containing lead structures against drought stress in crops interacting with RCAR/(PYR/PYL) receptor proteins were identified starting from in-depth SAR studies of related sulfonamide lead structures and protein docking studies. A converging 6-step synthesis via phosphinic chlorides and phosphono chloridates as key intermediates afforded envisaged tetrahydroquinolinyl phosphinamidates and phosphonamidates. Whilst tetrahydroquinolinyl phosphonamidates 13a,b exhibited low to moderate target affinities, the corresponding tetrahydroquinolinyl phosphinamidates 12a,b revealed confirmed strong affinities for RCAR/ (PYR/PYL) receptor proteins in Arabidopsis thaliana on the same level as essential plant hormone abscisic acid (ABA) combined with promising efficacy against drought stress in vivo (broad-acre crops wheat and canola).

An Increase in Vigorous but Not Moderate Physical Activity Makes People Feel They Have Changed Their Behavior.

Objective: While behavioral recommendations regarding physical activity commonly focus on reaching demanding goals by proposing "thresholds," little attention has been paid to the question of how much of a behavioral change is needed to make people feel that they have changed. The present research investigated this relation between actual and felt behavior change. Design: Using data from two longitudinal community samples, Study 1 and Study 2 comprised 614 (63% women) and 398 participants (61% women) with a mean age of 40.9 years (SD = 13.6) and 42.5 years (SD = 13.4), respectively. Using a stage-approach, participants were classified into four groups by asking them at the respective second measurement to indicate whether they had become more physically active since their last participation 6 months ago ("Changers"), they had tried but did not succeed in becoming more physically active ("Attempters"), they were already physically active on a regular basis ("Regular Actives"), or they had not tried to become more physically active ("Non-Attempters"). Physical activity was measured using the International Physical Activity Questionnaire (IPAQ), and fitness level was assessed as physical working capacity (PWC) via bicycle ergometry. Mixed ANOVAs including Time and Perceived Change as within and between factors were conducted, followed up by simple effect analyses. Results: Participants stating to have become more active in the past 6 months (Changers) showed a significant increase in vigorous physical activity but not in moderate physical activity, with an average of 6.8 (Study 1) and 10.6 (Study 2) metabolic equivalent value-hours (MET-hours) per week in vigorous activity. Corroborating these findings, objective fitness also significantly increased in the group of Changers. No systematic change in moderate or vigorous physical activity was observed for the three other "non-changer" groups (Regular actives, Attempters, Non-Attempters). Conclusion: The intensity of physical activity is the crucial variable for people's perception of change in physical activity. Moderate physical activity seems not to be perceived as an effective means for behavior change. It thus might fail to unfold sufficient motivational impact, despite its known positive effects on health.

Identifying new lead structures to enhance tolerance towards drought stress via high-throughput screening giving crops a quantum of solace.

Novel synthetic lead structures interacting with RCAR/(PYR/PYL) receptor proteins were identified based on the results of a high-throughput screening campaign of a large compound library followed by focused SAR studies of the three most promising hit clusters. Whilst indolinylmethyl sulfonamides 8y,z and phenylsulfonyl ethylenediamines 9y,z showed strong affinities for RCAR/ (PYR/PYL) receptor proteins in wheat, thiotriazolyl acetamides 7f,s exhibited promising efficacy against drought stress in vivo (wheat, corn and canola) combined with confirmed target interaction in wheat and arabidopsis thaliana. Remarkably, binding affinities of several representatives of 8 and 9 were on the same level or even better than the essential plant hormone abscisic acid (ABA).

Relevance of the Thought-Shape Fusion Trait Questionnaire for healthy women and women presenting symptoms of eating disorders and mixed mental disorders.

Thought-shape fusion (TSF) describes the experience of marked concerns about body weight/shape, feelings of fatness, the perception of weight gain, and the impression of moral wrongdoing after thinking about eating fattening/forbidden foods. This study sets out to evaluate the short version of the TSF trait questionnaire (TSF). The sample consists of 315 healthy control women, 244 women with clinical and subthreshold eating disorders, and 113 women with mixed mental disorders (mixed). The factor structure of the TSF questionnaire was examined using exploratory and subsequent confirmatory factor analyses. The questionnaire distinguishes between a Concept scale and a Clinical Impact scale. However, a lack of measurement invariances refers to significant differences between groups in terms of factor loadings, thresholds, and residuals, which questions cross-group validity. Results indicate that the concept is understood differently in the 3 groups and refers to the suitability of the questionnaire primarily for individuals presenting with symptoms of eating disorders.

Cognitive Distortions Associated with Imagination of the Thin Ideal: Validation of the Thought-Shape Fusion Body Questionnaire (TSF-B).

Thought-shape fusion (TSF) describes the experience of body-related cognitive distortions associated with eating disorder (ED) pathology. In the laboratory TSF has been activated by thoughts about fattening/forbidden foods and thin ideals. This study aims at validating a questionnaire to assess the trait susceptibility to TSF (i.e., body-related cognitive distortions) associated with the imagination of thin ideals, and developing an adapted version of the original TSF trait questionnaire, the Thought-Shape Fusion Body Questionnaire (TSF-B). Healthy control women (HC, n = 317) and women diagnosed with subthreshold and clinical EDs (n = 243) completed an online-questionnaire. The factor structure of the TSF-B questionnaire was examined using exploratory (EFA) and subsequent confirmatory factor analysis (CFA). EFA pointed to a two-factor solution, confirmed by CFA. Subscale 1 was named Imagination of thin ideals, containing five items referring to the imagination of female thin ideals. Subscale 2 was named Striving for own thin ideal, with seven items about pursuing/abandoning attempts to reach one's own thin ideal. The total scale and both subscales showed good convergent validity, excellent reliability, and good ability to discriminate between individuals with subthreshold/clinical EDs and HCs. Results indicate that cognitive distortions are also related to the imagination of thin ideals, and are associated with ED pathology. With two subscales, the TSF-B trait questionnaire appropriately measures this construct. Future studies should clarify whether TSF-B is predictive for the development and course of EDs. Assessing cognitive distortions with the TSF-B questionnaire could improve understanding of EDs and stimulate the development of cognitively oriented interventions. CLINICAL TRIAL REGISTRATION NUMBER: DRKS-ID: DRKS00005709.

Acute toxicity study and effect of prolonged administration (28 days) of crude ethanolic root extract of Diospyros mespiliformis Hochst (Ebenaceae) on clinical, haematological and biochemical parameters of albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Different parts of the plant Diospyros mespiliformis have been used traditionally for the treatment of ailments in Nigeria particularly among the Kamwe people of Michika local government area of Adamawa State where the root has been used as an anti-malarial for ages. Most of the uses have been without any scientific evidence and toxicological assessment. The present study aimed to determine acute toxicity profile as well as the effect of prolonged administration of the extract on clinical, haematological and biochemical parameters of albino rats. MATERIALS AND METHODS: Thirty and twenty-five Wistar rats of both sexes and of varying weights were, respectively, used for acute toxicity study and prolonged administration study of crude ethanolic root extract of Diospyros mespiliformis. The rats used for both studies were each administered graded concentrations of the extract (100, 200, 400, 800 and 1600mg/kg) for acute toxicity testing and (50, 100, 200 and 400mg/kg) for the study of the effect of prolonged administration. The rats used for acute toxicity study were observed for a period of 24h for signs of toxicity and eventual death while parameters for prolonged study were recorded at weekly interval starting from day zero up to day 28 post administration. RESULTS: The extract produced an intraperitoneal LD50 of 570mg/kg. Body weight changes were not statistically significant (p>0.05) while haematological parameters (packed cell volume (PCV)), haemoglobin concentration (Hb), red blood cells (RBC), white blood cells (WBC) and differential leucocyte counts (DLC) were significantly modulated (p>0.05) after administration. Haematological indices (mean corpuscular volume (MCV)), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentrations (MCHC) were similarly modulated significantly (p>0.05). CONCLUSIONS: The extract appeared to be moderately toxic while prolonged administration improved the blood parameters of rats, suggesting that the plant׳s extract at lower doses can be used for a prolonged period, without deleterious effect on the haematological profile and serum enzymes.

Prevalence of Intestinal Parasites among Pupils in Rural North Eastern, Nigeria.

BACKGROUND: The study determined the prevalence of intestinal parasitism among pupils in rural schools (Almajiris) in Konduga local Government Area of Borno state. MATERIALS AND METHODS: A total of 257 stool specimens were collected at random among pupils (Almajiris) in rural quranic schools; the stools were processed and examined both macroscopically and microscopically by concentration techniques. RESULTS: The prevalence of intestinal parasitism among the Almajiris was 80.9%. The highest prevalence rate was 97.8% while the least prevalence was 67.4%. The 6-8 years age group had the highest prevalence of 85.7% while the least prevalence of 77.7% in the 13-16years age bracket. Ascaris lumbricoides had the highest prevalence of (19.1%) while Trichuris trichiura had the least prevalence of (3.5%). Thirteen pupils in the 5-8 years had multiple parasites; multiple parasitism also occurred in 22 pupils aged 9-12 years and in 11 pupils aged 13-16 years. CONCLUSION: There is a high prevalence rate of intestinal parasites with attendant risk of intestinal obstruction among the Almajiris in rural north eastern Nigeria.

Multicenter evaluation of PCR methods for detecting CMV DNA in blood donors.

BACKGROUND: CMV DNA screening may be a useful adjunct to serologic tests in distinguishing potentially infectious blood donations from those that are "CMV-safe." However, there is currently no consensus on the optimal assay method for accurate detection of CMV DNA in donors. STUDY DESIGN AND METHODS: A blinded multicenter evaluation of seven CMV PCR assays was performed by five laboratories by using coded sets of analytical controls and donor blood samples. RESULTS: Five assays displayed sufficient sensitivity for donor screening, as judged by consistent detection of a minimum of 25 CMV genome equivalents (geq) in analytical controls constructed to contain from 1 to 100 CMV geq in background DNA from 250,000 cells, while the other two assays displayed inadequate sensitivity. Three sensitive assays, two based on nested PCR directed at the UL93 and UL32 regions of the CMV genome and another test (Monitor Assay, Roche), did not detect CMV DNA in samples from any of 20 pedigreed CMV-seronegative, Western blot-negative (S-/WB-) donors. Two other assays based on nested PCR occasionally detected CMV DNA in S-WB- samples, and one sensitive nested PCR assay directed at UL123 detected CMV DNA in a large proportion (85%) of S-WB- samples. CONCLUSION: Seven CMV PCR assays currently used for research and/or diagnostic applications displayed marked variations in sensitivity, specificity, and reproducibility when applied to coded analytical and clinical control samples containing cellular DNA from the equivalent of 250,000 WBCs. These results will be useful in the selection of assays with performance characteristics appropriate to donor screening objectives. They may also help explain discrepant findings from previous studies that used PCR to determine CMV DNA prevalence in seronegative and seropositive blood donors.

The effect of leukocyte-reduction method on the amount of human cytomegalovirus in blood products: a comparison of apheresis and filtration methods.

This study examined the effectiveness of 3 leukocyte-reduction (LR) methods in depleting the residual level of cytomegalovirus (CMV) in blood products measured by quantitative polymerase chain reaction (QA-PCR). At 2 locations over 3 allergy seasons, apheresis platelets and whole blood were collected from 52 healthy CMV seropositive subjects having an elevated titer of CMV DNA (median = 2400 genome equivalents [GE]/mL) resulting in 32 evaluable LR apheresis platelets, 31 filtered platelets from whole blood, and 31 filtered red blood cells (RBCs) from whole blood. Leukoreduction by apheresis and filtration resulted in substantial reduction of detectable CMV DNA levels with 99.9% of the LR products expected to have less than 500 GE/mL of CMV DNA. No difference was found between methods (P =.52). CMV genomic leukocyte subset localization was determined by QA-PCR of fluorescence-activated cell sorter (FACS)-sorted peripheral blood from 20 seropositive subjects (n = 10 > 100 GE/mL, n = 10 QA-PCR negative). CMV was detected in monocyte (13 of 20) and granulocyte (3 of 20) fractions. Presence of competent virus in QA-PCR positive (> 100 GE/mL) peripheral blood samples was verified with 4 of 19 subjects positive in shell vial assay, and 8 of 18 positive for CMV gene products (messenger RNA). We observed a seasonal DNAemia variation in seropositive subjects. CMV seropositive subjects (n = 45) entered into longitudinal monitoring in March/April 1999 were QA-PCR negative at baseline. Subjects converted to a positive QA-PCR coincident with increased seasonal allergen levels (Norfolk 15 of 18 evaluable in 43.4 +/- 9.48 days; Denver, 16 of 23 evaluable in 96 +/- 26.3 days). These data demonstrate effective reduction of CMV load by LR during periods of DNAemia in CMV seropositive subjects. (Blood. 2001;97:3640-3647)

Decreased T cell precursor frequencies to Epstein-Barr virus glycoprotein Gp110 in peripheral blood correlate with disease activity and severity in patients with rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic joint disease associated with certain HLA-DR alleles expressing the QK/RRAA motif or shared epitope. The Epstein-Barr virus (EBV) has been suspected to be a causative factor for RA. The EBV gp110, a glycoprotein of the replicative cycle that contains a copy of the shared epitope, constitutes an important target in the immune control of EBV replication. This study evaluated the specific T cell response to EBV gp110 in patients with RA expressing or not the shared epitope and examined whether this immune cellular response might be related to disease activity and severity. METHODS: 25 patients with RA were studied and compared with 25 healthy controls. Disease activity was assessed by biochemical markers of inflammation (erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) levels). Disease severity was defined by extra-articular disease (vasculitis, subcutaneous nodules, or other organ disease). The frequencies of peripheral blood T cells specific for EBV gp110 and a control protein (total protein extract from Escherichia coli) were determined by direct limiting dilution analysis without preliminary bulk culture. RESULTS: The gp110 precursor frequencies ranged from 0 to 20 x 10(-6) in patients with RA and controls. The mean gp110 T cell precursor frequency was lower in patients with RA (SD 3.2 (4.4) x 10(-6)) than in healthy controls (4.1 (3.8) x 10(-6)) (p = 0.02). No difference was found for the control protein (p = 0.09). Both shared epitope positive and negative patients with RA responded to gp110, without significant difference. A negative correlation between both ESR and CRP levels and the gp110 T cell response was found (r = -0.71, p<0.0001 and r = -0.42, p = 0.038, respectively). Finally, patients with extra-articular disease displayed the lowest immune cellular response to EBV gp110. CONCLUSION: These results suggest that patients with RA have a decreased T cell response to EBV gp110. Since gp110 is an important protein in the control of EBV replication, this might lead to a poor control of EBV infection, chronic exposure to other EBV antigens, and thus to a chronic inflammatory response in patients with RA.

Expression of heat shock proteins 72/73 in human peritoneal mesothelial cells in vivo and in vitro.

Leukocyte accumulation during peritonitis leads to an injurious microenvironment which is involved in the host defense reaction but is also thought to cause peritoneal damage. We tested the hypothesis that mesothelial cells (MC) respond to the injurious microenvironment during peritonitis by an increased expression of heat shock proteins (HSP 72/73), a basic way by which cells are protected against injury. Comparison of resting MC and activated MC during peritonitis in vivo by means of immunohistochemistry revealed an increased expression of HSP 72/73. As assessed by Western immunoblotting, incubation of MC in vitro with tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) caused a time-dependent induction of HSP 72/73 expression, which was maximal 6 h after stimulation. We suggest that the increased HSP 72/73 expression of MC during peritonitis is in part induced by TNF-alpha and IL-1beta and may exert a cell-protective function, lessening MC damage during peritonitis.

HLA-DR polymorphism influences T-cell precursor frequencies to Epstein-Barr virus (EBV) gp110: implications for the association of HLA-DR antigens with rheumatoid arthritis.

To study whether HLA-DR haplotypes associated with susceptibility to develop rheumatoid arthritis (RA) may influence T-cell responses to the Epstein-Barr virus (EBV) gp110 (a protein of the late replicative cycle of EBV), we evaluated the frequency in peripheral blood of T cells capable to proliferate to EBV gp110 by direct limiting dilution analysis in 50 HLA-DR-typed healthy subjects. NVe found that HLA-DRB1*07, an allele associated with reduced risk to develop RA, is associated with the highest frequencies of T cells specific for gp110 in peripheral blood. In contrast, HLA-DRB1*0404, one of the susceptibility alleles is associated with the lowest frequencies of gp110 specific T cells. Finally, people expressing both HLA-DRB1*07 and HLA-DRB1*0404 display low precursor frequencies to EBV gp110.

Human herpesvirus-6 (HHV-6)-associated necrotizing encephalitis in Griscelli's syndrome.

We report a male caucasian German pediatric patient of no Arab or Mediterranean ancestry with virus associated CNS lesions in Griscelli's syndrome (GS; McKusick No. 214450). The boy presented with recurrent infections, and meningitis with subsequent progressive signs of increased intracranial pressure leading to death at 32 weeks of age. At autopsy, various sites of the CNS revealed necroses in gray and white matter. CNS histology revealed numerous and massive predominantly perivascular CD8 positive lymphohistiocytic infiltrates. These findings were associated strictly with the presence of human herpesvirus-6 (HHV-6) genome or the HHV-6 specific late antigen H-AR 3, found in neurons, oligodendrocytes, and astrocytes. The search for HHV-6 replication dependent antigen, HHV-7 DNA, CMV, adenovirus, Coxsackie B1, B2, and B4-antigens, and mycobacteria was not successful. Detection of viruses was attempted using immunohistochemistry, in situ hybridization or nested polymerase chain reaction, respectively. Lymphocyte typing was carried out immunohistochemically. In GS, virus induced CNS damage does not seem to require necessarily active virus replication. It may also appear as a consequence of an immune reaction triggered by antigen expression.

Epstein-Barr virus (herpesvirus 4) types A, B and herpesvirus-6 variants A and B in patients presenting with recurrent upper respiratory inflammation, persistent paravertebral thoraco-lumbar muscle spasm and fatigue by polymerase chain reaction (PCR).

DNA from Epstein-Barr virus (EBV) Types A, B and Herpesvirus-6 (HHV-6) Variants A and B was detected by the Polymerase chain reaction (PCR) in the saliva of 51 non-immunocompromised donor patients and in the blood of seventy non-immunocompromised donor patients with specific signs and symptoms. The minimum selection criteria for each patient included acute or recurrent upper respiratory infection, unilateral thoracolumbar muscle spasm and fatigue. PCR DNA detection in the saliva of selected donors revealed 80% of the donors had either Type A or B EBV (41 of 51), 34.1% Type B EBV only (14 of 41), 9% Type A only (4 of 41), and 56.1% Type A and B EBV (23 of 41). HHV-6 DNA was detected in 45.0% (23 of 51). PCR for EBV in blood of selected donors revealed 68.5% Type A or B EBV (48 of 70), 0% type B EBV alone, 64.8% Type A EBV only (31 of 48) and 35.4% both Type A and B EBV (17 of 48). HHV-6 was detected in 96.4% (64 of 70). The association of Type B EBV in the pathogenesis of these patients is explored based on the PCR quantitation of B type EBV DNA present in the samples.

Human herpesvirus-6 (HHV-6) in Hodgkin's disease: cellular expression of viral antigens as compared to oncogenes met and fes, tumor suppressor gene product p53, and interleukins 2 and 6.

Patients with Hodgkin's disease (HD) frequently show elevated serum titers against human herpersvirus-6 (HHV-6) and their tissues contain significantly increased numbers of cells with HHV-6 DNA. This may coincide with similar data of Epstein-Barr virus (EBV) infections. According to in vitro studies, Hodgkin- and Reed-Sternberg (RS) cells can be infected by HHV-6 and may be coinfected by HHV-6 and EBV. Both viruses are potentially oncogenic and also may interfere with the production of various cytokines. We now demonstrate by using immunohistological methods that HHV-6 antigens are present in 77.3% of the HD lymphomas, 37% of which contain the replication-associated p41 "early-late" antigen and 63% the late membrane antigen complex gp116/64/54. Monocytic cell populations including HD and RS cells are most frequently antigen-positive, while lymphoid cells are less frequently. These cells also express IL-6 and IL-6 receptors as well as the IL-2 receptor a chain (CD25), while only occasionally the IL-2 receptor beta chain (p70). IL-6 receptors are significantly more frequently expressed than IL-6 itself. HD and RS cells constitute a significant pool of proliferating cells as reflected by their 95% positivity for PCNA, yet tumor suppressor genes are found in only 21% and the proto-oncogenes fes and met are expressed in various types of cells. The data may indicate that both viruses possibly contribute to the course of the disease through polyclonal stimulations of cell proliferation and coincident dysregulation of the cytokine network control of cell function and proliferation. A direct oncogenic effect of EBV and HHV-6 in HD appears less probable.