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Biomedical subjects

David I Bernstein

Publications and source records attributed to David I Bernstein.

At least 55 records · Page 3Linked to original sources
PubMed2004

Rotavirus immunoglobulin a responses stimulated by each of 3 doses of a quadrivalent human/bovine reassortant rotavirus vaccine.

A quadrivalent precursor to the pentavalent rotavirus vaccine candidate RotaTeq was evaluated in a 3-dose, 439-subject study. To determine immunogenicity, the quantity of rotavirus immunoglobulin A (IgA) in stool specimens obtained, at 1 of 10 study sites, from 37 placebo and 37 vaccine recipients was measured. None of the placebo recipients showed a clinically important (>/=3-fold) increase in stool rotavirus IgA, whereas 31 vaccine recipients showed an increase after at least 1 dose of vaccine. In total, 16, 19, and 15 vaccine recipients had increases after 1, 2, and 3 doses, respectively, indicating that a 3-dose regimen increased the immune response elicited by this vaccine.

Animals↗
PubMed2004

Protection against congenital cytomegalovirus infection and disease in guinea pigs, conferred by a purified recombinant glycoprotein B vaccine.

Glycoprotein B (gB) has emerged as a subunit-vaccine candidate for congenital cytomegalovirus (CMV) infection, a major public health problem. The present study evaluated a cloned, recombinant gB vaccine in the guinea pig cytomegalovirus (GPCMV) model of congenital infection. Guinea pigs were immunized with gB, which was coadministered with either Freund's adjuvant or alum. All gB-immunized dams had enzyme-linked immunosorbent-assay and neutralizing-antibody responses, with significantly higher titers in the gB/Freund's group. Pregnant dams were challenged with GPCMV subcutaneously during the 3rd trimester. Maternal DNAemia on day 10 after infection trended lower in gB-immunized dams than in control animals, with significant reductions in the gB/Freund's group. Vaccination resulted in a highly significant reduction in pup mortality. For the gB-vaccine groups, pup mortality was significantly lower, and reduced rates of GPCMV transmission were noted, for dams immunized with gB and Freund's adjuvant, compared with dams immunized with gB and alum. These are the first data indicating that a recombinant gB vaccine protects against congenital CMV infection and disease.

Adjuvants, Immunologic↗
PubMed2004

Treatment of herpes simplex virus infections.

Herpes simplex virus (HSV) types 1 and 2 are ubiquitous organisms that cause infections in human populations throughout the world. The clinical manifestations of HSV infections are varied, ranging from asymptomatic disease to life-threatening illness in neonates and immunocompromised hosts. This article will review the common presentations for HSV disease and the current recommendations for the treatment of these infections. A detailed summary of the antiviral drugs used to treat HSV infections is also presented.

Antiviral Agents↗
PubMed2004

Twelve-year survey of fatal reactions to allergen injections and skin testing: 1990-2001.

BACKGROUND: Fatal reactions associated with skin testing and injection immunotherapy have not been surveyed in North America since 1989. OBJECTIVE: A survey of fatal reactions related to skin testing and immunotherapy and of near-fatal immunotherapy reactions that transpired from 1990 through 2001 was conducted among member practices of the American Academy of Allergy, Asthma and Immunology. METHODS: A short survey of fatal reactions was sent to all American Academy of Allergy, Asthma and Immunology physicians, and an 87-item follow-up detailed questionnaire was sent to those reporting fatal reactions. RESULTS: Of 2404 members, 646 (25%) responded to the short survey. There were 20 fatal immunotherapy reactions that were directly reported and 21 indirectly reported cases by local physicians. There were 273 (42% of the responding sample) reports of near-fatal reactions. It was estimated that fatal reactions occurred every 1 per 2.5 million injections, with an average of 3.4 deaths per year. One fatality was confirmed after skin prick testing with multiple food allergens. Of 17 fatal deaths described in long questionnaires, 15 were in asthmatic patients, the majority of whose symptoms were not optimally controlled. Three reactions occurred in a medically unsupervised setting. None were receiving beta-blockers, and one was taking an angiotensin-converting enzyme inhibitor. Most fatal reactions (59%) occurred with maintenance allergen doses. The onset of 3 reactions began more than 30 minutes after injections, with a significant delay in starting epinephrine. Epinephrine was not administered in 3 other fatal reactors. CONCLUSIONS: Fatal reactions to immunotherapy injections occurred at similar rates reported in previous surveys. Certain clinical practices have improved (ie, exclusion of beta-blockers), and dosing errors were infrequent. Fatal reactions to immunotherapy often occur in settings inappropriate for optimal treatment of anaphylaxis. Strict adherence to practice guidelines might prevent or minimize future fatal reactions.

Asthma↗
PubMed2004

Safety, efficacy, and immunogenicity of a live, quadrivalent human-bovine reassortant rotavirus vaccine in healthy infants.

OBJECTIVES: To investigate safety, efficacy, and immunogenicity of live quadrivalent rotavirus vaccine (QRV) containing human-bovine (WC3) reassortant rotavirus serotypes G1, G2, G3, and P1a. STUDY DESIGN: This was a randomized, double-blinded, placebo-controlled trial. During 1993 to 1994, at 10 US study sites, 439 healthy infants approximately 2 to 6 months of age, were enrolled to receive 3 doses of oral QRV or placebo at approximately 8-week intervals. RESULTS: The vaccine was generally well tolerated; no serious vaccine-related adverse experiences were reported. Risk differences and 95% confidence intervals suggested no differences between vaccine and placebo recipients in the incidences of fever, irritability, vomiting, or diarrhea during the 14 days after any dose. QRV was 74.6% efficacious (95% CI: 49.5%, 88.3%) in preventing rotavirus acute gastroenteritis (AGE), regardless of severity and 100% efficacious (95% CI: 43.5%, 100%) in preventing severe rotavirus AGE through one rotavirus season. Serotype G1 was identified in most infants with rotavirus AGE. A >or=3-fold rise in serum neutralizing antibody to G1 was observed in 57% (45/79) of vaccinees. A >or=3-fold rise in serum anti-rotavirus IgA and fecal anti-rotavirus IgA was observed in 88% (162/185) and 65% (104/159) of vaccinees, respectively. CONCLUSIONS: QRV was generally well tolerated, immungenic, and highly effective against rotavirus gastroenteritis.

Animals↗
PubMed2004

Advances in methods used in evaluation of occupational asthma.

PURPOSE OF REVIEW: Diagnosing occupational asthma (OA) is a complex undertaking, the primary goal of which is to demonstrate a causal relation between exposure to a specific agent encountered at work and asthmatic responses. Recent development or refinement of diagnostic tools may improve the diagnostic accuracy, which may have important economic and social consequences for both employers and workers. RECENT FINDINGS: Although specific inhalation challenge (SIC) testing is the gold standard for diagnosis of OA, these tests are not widely available in many countries. Thus, new less invasive techniques used in the measurement of airway inflammation, such as exhaled nitric oxide and induced sputum are highlighted as are recent developments in both in vivo and in vitro immunologic testing. SUMMARY: Although new perspectives are being evaluated, the diagnosis of occupational asthma still relies mostly on specific inhalation challenge. Further studies are required to confirm the utility of these new techniques in the diagnosis of OA.

Asthma↗
PubMed2004

Comparison of adolescent and young adult self-collected and clinician-collected samples for human papillomavirus.

OBJECTIVE: To examine the concordance between self-collected and clinician-collected samples for human papillomavirus (HPV) DNA. METHODS: Sexually active adolescent and young adult women aged 14-21 years (N = 101) were enrolled in a prospective cohort study of HPV testing. Participants self-collected vaginal samples for HPV DNA, and clinicians collected cervicovaginal samples for HPV DNA and a cervical cytology specimen. We determined concordance between the results of self- and clinician-collected specimens using a kappa statistic and McNemar's test. RESULTS: Of the 51% of participants who were HPV positive, 53% had 1 type, 25% had 2 types, and 22% had 3 types or more; 25 different HPV types were identified. Self-collected samples detected more participants with HPV than clinician-collected samples (45% versus 42%, P =.65). When results were categorized into presence or absence of high-risk HPV types, agreement between self- and clinician-collected specimens was high (kappa 0.72) and the difference between test results was not significant (McNemar's P =.41). However, when all HPV types detected were considered, agreement was perfect in only 51% of those with 1 or more types of high-risk HPV type. There was no association between agreement and age or HPV type. CONCLUSION: Self testing for HPV DNA may be sufficiently sensitive for the detection of high-risk HPV DNA among adolescent and young adult women in clinical settings.

Adolescent↗
PubMed2004

Return for results after herpes simplex virus type 2 screening.

OBJECTIVE: The objective of this study was to evaluate factors associated with return for results of type-specific herpes simplex virus (HSV) screening. METHODS: Participants receiving type-specific HSV testing were asked to return for results 2 weeks after testing. Predictors of return included demographics, herpes-related knowledge and attitudes, and past sexual behaviors. RESULTS: A total of 820 sexually active subjects (age, 14-30 years; 41% male) received HSV screening and 578 (70%) returned for results. Higher probability of return for HSV testing results was significantly associated with older age (odds ratio [OR], 1.06), female gender (OR, 1.57), enrollment at sites other than the county sexually transmitted disease clinic (OR, 1.70-4.71), and heightened level of perceived HSV vulnerability (OR, 1.07). Lower probability of return was associated with having more than 1 recent sex partner (OR, 0.46). CONCLUSIONS: Lower rates of return of high-risk patients suggest the need to focus resources on receipt of test results.

Adolescent↗
PubMed2004

Factors predicting the acceptance of herpes simplex virus type 2 antibody testing among adolescents and young adults.

BACKGROUND: The rates and determinants of acceptance of herpes simplex virus type 2 (HSV-2) testing have not been adequately studied. OBJECTIVES: The objective of this study was to identify factors associated with acceptance of HSV-2 antibody testing in individuals with no history of genital herpes. STUDY: We conducted a cross-sectional survey study followed by the offer of free HSV-2 serologic testing at an urban sexually transmitted disease (STD) clinic, 2 general adult medical clinics, an urban university campus, and an urban adolescent medicine clinic. A total of 1199 individuals aged 14 to 30 years completed the survey and were offered testing. RESULTS: A total of 68.4% accepted HSV-2 testing. Factors independently associated with acceptance were female sex, older age, having an STD history, having 1 or more sexual partners in the last 6 months, perceived vulnerability to HSV-2 infection, and perceived benefits of HSV-2 testing. Fear of needles predicted rejection of testing, as did attending a general medical clinic versus an STD clinic and nonwhite race. CONCLUSION: There is a substantial interest in HSV-2 antibody testing across a variety of settings. Those at greatest behavioral and historic risk for HSV-2 infection, women, and persons whose health beliefs are consistent with testing are more likely to accept serologic testing when it is offered.

Adolescent↗
PubMed2004

Predictors of herpes simplex virus type 2 antibody positivity among persons with no history of genital herpes.

BACKGROUND: The demographic, historical, and behavioral factors that predict a positive herpes simplex virus type 2 (HSV-2) antibody test in persons without a history of genital herpes have not been well-defined. METHODS: Individuals (age 14-30 years) without a history of genital herpes completed a questionnaire and were offered free HSV-2 antibody testing. Factors from the questionnaire were correlated with the HSV-2 antibody result. RESULTS: Univariate analysis showed that female gender was significantly associated with positive test results. In gender-specific, multiple logistic regression models, a positive HSV-2 antibody test among men was associated with older age, non-white race, and a history of sexually transmitted disease (STD). Gender-specific symptom scores from the questionnaire were not predictive in either gender, but the gender-common symptom score was marginally predictive of a positive HSV-2 antibody test in women. Among women, older age, non-white race, and STD history predicted a positive test. CONCLUSIONS: Among young persons with no history of genital herpes who agreed to HSV-2 antibody testing, increasing age, non-white race, and a history of an STD were predictors of a positive test. A history of frequent pain, itching, burning, and rashes in the anogenital region was marginally associated with positive HSV-2 tests in women. These results might help guide selective use of HSV-2 antibody screening.

Adolescent↗
PubMed2004

Antibody-mediated neutralization of pertussis toxin-induced mitogenicity of human peripheral blood mononuclear cells.

Antibody-mediated neutralization of pertussis toxin-induced proliferation of human peripheral blood mononuclear cells (PBMC) was assessed using alamarBlue and compared with results from the Chinese hamster ovary (CHO) cell assay using sera from vaccinated adults and convalescent children. Neutralization values for the CHO assay were similar for vaccinated and convalescent subjects; however. the convalescent group had higher titers in the PBMC assay. Results for pertussis toxin neutralization with the CHO assay appear to be distinct from those with the PBMC assay.

Animals↗
PubMed2004

Acellular pertussis vaccines and complement killing of Bordetella pertussis.

Antibody-dependent complement killing of Bordetella pertussis after immunization with a three-component acellular pertussis vaccine was characterized. Postimmunization activity was unchanged for about half of the adult vaccine recipients. The responses of the other individuals were complex, with evidence of both beneficial and antagonistic responses occurring, sometimes in the same individual.

Antibodies, Bacterial↗
PubMed2003

Preconception vaccination with a glycoprotein B (gB) DNA vaccine protects against cytomegalovirus (CMV) transmission in the guinea pig model of congenital CMV infection.

DNA vaccines expressing the guinea pig cytomegalovirus (GPCMV) homologs of the glycoprotein B (gB) and UL83 proteins were evaluated for protection against congenital GPCMV infection. After 4 doses of DNA administered by epidermal (gene gun) route, all guinea pigs developed enzyme-linked immunosorbent assay (ELISA) antibody and, for gB-vaccine recipients, neutralizing antibody. Dams were challenged with 1 x 10(4) plaque-forming units of GPCMV in the third trimester. Preconception vaccination with gB did not decrease overall pup mortality, although, within the gB-vaccine group, pup mortality was lower among dams with high ELISA responses. Preconception maternal vaccination with gB vaccine significantly reduced congenital transmission in liveborn pups. In contrast, UL83 vaccine had no significant effect on pup mortality or vertical transmission of GPCMV. Virus load was significantly lower in infected pups born to gB- and UL83-vaccinated dams than in infected pups born to control dams. These data support the concept that subunit gB vaccination may be useful in protecting against CMV-induced disease.

Animals↗
PubMed2003

Herpes simplex virus (HSV) type 2 glycoprotein D subunit vaccines and protection against genital HSV-1 or HSV-2 disease in guinea pigs.

In two recent clinical trials, a vaccine containing herpes simplex virus (HSV) type 2 glycoprotein D (gD2) and a novel adjuvant AS04 comprising alum (Al) and 3-deactylated monophosphoryl lipid A (3-dMPL) afforded HSV-seronegative women significant protection against HSV-2 genital disease (vaccine efficacy, 73% in study 1 and 74% in study 2) and limited protection against infection (46% in study 1 and 39% in study 2). In the present report, studies in the guinea pig model investigated the protection afforded by gD2/AS04 against HSV-1 and HSV-2 genital herpes and investigated whether immunization could prevent or reduce recurrent disease in guinea pigs that developed mucosal infection. Immunization with gD2/AS04 conveyed nearly complete protection against primary disease with either virus but did not prevent mucosal infection. Guinea pigs immunized with gD2/AS04 were significantly better protected against recurrent disease than were guinea pigs immunized with a gD2/Al vaccine, which suggests that inclusion of 3-dMPL improved protection against latent infection.

Animals↗
PubMed2003

Quantitative-competitive PCR monitoring of viral load following experimental guinea pig cytomegalovirus infection.

Human cytomegalovirus (HCMV) is the most common cause of congenital viral infection in the developed world, and can lead to significant morbidity. Animal models of HCMV infection are required for study of pathogenesis, because of the strict species-specificity of cytomegalovirus (CMV). Among the small animal CMV models, the guinea pig CMV (GPCMV) has unique advantages, in particular its propensity to cross the placenta, causing disease in utero. In order to develop quantitative endpoints for vaccine and antiviral therapeutic studies in the GPCMV model, a quantitative-competitive PCR (qcPCR) assay was developed, based on the GPCMV homolog of the HCMV UL83 gene, GP83. Optimal amplification of GPCMV DNA was observed using primers spanning a 248 base pair (bp) region of this gene. A 91 bp deletion of this cloned fragment was generated for use as an internal standard (IS) for PCR amplification. Standard curves based upon the fluorescent intensity of full-length external target to IS were compared with signal intensity of DNA extracted from blood and organs of experimentally infected guinea pigs in order to quantify viral load. Viral load in newborn guinea pigs infected transplacentally was determined and compared with that of pups infected with GPCMV as neonates. Viral loads were highest in pups infected as neonates. The most consistent isolation and highest quantities of viral DNA were observed in liver and spleen, although viral genome could be readily identified in brain, lung, and salivary gland. Viral load determination should be useful for monitoring outcomes following vaccine studies, as well as responses to experimental antiviral agents.

Animals↗
PubMed2003

An animal model of neonatal cytomegalovirus infection.

Cytomegalovirus (CMV) is the most common cause of congenital infection in the developed world and can lead to a life-threatening disease. We therefore developed an animal model to evaluate candidate anti-CMV drugs and to further define the pathogenesis of CMV infections. Newborn guinea pigs were infected by intraperitoneal administration of 10(6) pfu of a virulent salivary gland (SG) passaged guinea pig CMV (gpCMV) within 48 h of birth. Inoculation of animals produced 50% overall mortality. A lack of weight gain was also a hallmark of infection. By day 14 after inoculation the weight of gpCMV-infected animals was significantly less than controls (152.9+/-45 g versus 254.7+/-38.5 g, P<0.0001). The most consistent isolation and highest titers of virus were found in the liver and spleen early while lung titers were maximal at day 10. A quantitative competitive PCR (qcPCR) assay confirmed the presence of a high CMV viral load in infected organs. Antiviral treatment with cyclic HPMPC (cHPMPC) for 7 days significantly reduced mortality (1/20 versus 14/20, P<0.001) and viral replication but did not improve weight gain. This model should be useful for further evaluations of the pathogenesis of CMV infections and for evaluation of antiviral drugs and vaccines.

Animals↗
PubMed2003

Occupational asthma caused by exposure to low-molecular-weight chemicals.

Chemical agents cause approximately 40% of cases of occupational asthma (OA). Diagnosis of OA caused by chemicals relies on the demonstration of decrements in lung function at the workplace or during a controlled specific inhalation challenge to the suspect chemical agent. Evaluation of workers is accomplished best with a stepwise algorithmic approach and while the worker is symptomatic and still exposed at work. An early diagnosis followed by cessation of exposure can result in asthma remission and is likely to prevent progression to chronic disabling obstructive disease.

Asthma↗