Biomedical subjects

Robert J Hopkins

Publications and source records attributed to Robert J Hopkins.

7 recordsLinked to original sources

PubMed2004

Safety and pharmacokinetic evaluation of intravenous vaccinia immune globulin in healthy volunteers.

BACKGROUND: Vaccinia immune globulin (VIG) administered via the intramuscular route has historically been used for the treatment of complications of smallpox vaccination. Intravenous formulations of VIG are required to improve tolerability and pharmacokinetic profile. METHODS: We conducted 2 separate studies to evaluate the feasibility of administration of an intravenous formulation of antivaccinia immune globulin (VIGIV). The first study assessed the pharmacokinetics and safety of a newly manufactured lyophilized VIG product for intravenous administration (VIGIV-lyo). Seventy-eight healthy volunteers received an intravenous infusion of VIGIV-lyo at doses of 100 mg/kg, 200 mg/kg, or 500 mg/kg. In the second study, we evaluated the safety of a liquid product of VIGIV (VIGIV-liq) in 33 healthy volunteers receiving an intravenous infusion of 100 mg/kg VIGIV-liq. RESULTS: The geometric mean titer of VIG at the target dose (100 mg/kg) after intravenous administration is 2.5 times higher than the predicted geometric mean titer after intramuscular injection (P<.001). The pharmacokinetics of VIGIV-lyo are linear for doses from 100 mg/kg through 500 mg/kg. Administration of the 200-mg/kg and 500-mg/kg doses of VIGIV-lyo does not result in markedly higher adverse event rates. The adverse event rates observed with the liquid product are comparable to those seen with the lyophilized product. CONCLUSIONS: These 2 studies suggest that intravenous administration of VIG is well tolerated and results in a more favorable pharmacokinetic profile than does VIG administered intramuscularly.

Antibodies, Viral↗

PubMed2004

Clinical efficacy of intramuscular vaccinia immune globulin: a literature review.

BACKGROUND: Numerous literature reports describe clinical efficacy of intramuscular vaccinia immune globulin (VIG) for complications of smallpox vaccination, prophylaxis of individuals with contraindications to vaccination, and prevention of smallpox among close contacts of patients with smallpox. METHODS: We reviewed the literature regarding VIG treatment and prophylaxis of smallpox vaccine complications and the use of VIG as a preventative measure for close contacts of patients with smallpox. RESULTS: Data regarding intramuscular administration of VIG for treatment of smallpox vaccine complications occurred in 16 articles, none of which reported formal controlled trials. The indications for treatment include generalized vaccinia, progressive vaccinia, eczema vaccinatum, and certain accidental implantations. Six publications suggest VIG efficacy for prophylaxis of vaccinial superinfection of eczema, burns, chickenpox, immunosuppression, pregnancy, or certain skin conditions. Prophylactic VIG has also been used in healthy military recruits to reduce the incidence of postvaccinial encephalitis. The use of intramuscular administration of VIG to prevent smallpox in contacts of patients with documented cases of smallpox is reported in 4 studies that compare contacts who received intramuscular administration of VIG with those who did not and in 1 observational study, with varying but promising results. CONCLUSIONS: Although controlled clinical trials do not exist to support the use of VIG for treatment of vaccinia-related complications or prophylaxis among individuals with contraindications to smallpox vaccination, available data suggest that VIG reduces morbidity and mortality associated with progressive vaccinia (vaccinia necrosum) and eczema vaccinatum. Furthermore, VIG seems to prevent vaccinial superinfection in patients with inflammatory skin diseases or burns, given the low incidence of vaccina-related complications associated with these conditions.

Antibodies, Viral↗

PubMed2004

Urticaria, exanthems, and other benign dermatologic reactions to smallpox vaccination in adults.

A phase 1 smallpox vaccine trial involving 350 adult volunteers was conducted. Of these subjects, 250 were naive to vaccinia virus vaccine (i.e., "vaccinia naive"). Volunteers received a new cell-cultured smallpox vaccine or a live vaccinia virus vaccine. Nine self-limiting rashes (3.6%) were observed in the vaccinia-naive group. None of the vaccinia-experienced patients had a rash. Rashes appeared 6-19 days after vaccination and had 5 different clinical presentations. Five volunteers had urticarial rashes that resolved within 4-15 days, 1 had an exanthem that lasted 20 days, and 1 each presented with folliculitis, contact dermatitis, and erythematous papules found only on the hands and fingers. Volunteers reported pruritus, tingling, and occasional headaches. Relief was obtained with antihistamine and acetaminophen therapy. No volunteer experienced fever or significant discomfort.

Adult↗

PubMed2003

Helicobacter pylori.

Explore the source record for details and available documents.

Anti-Bacterial Agents↗

PubMed2002

A liposome-based therapeutic vaccine against beta -amyloid plaques on the pancreas of transgenic NORBA mice.

Immune tolerance to beta-amyloid (Abeta) was broken in NORBA transgenic mice presenting Abeta plaques on their pancreases. Vaccination of Black C57, BALB/c, and NORBA mice with the synthetic Abeta(1-16) sequence modified by covalently attaching two palmitoyl residues at each end of the peptide, subsequently reconstituted in liposomes-Lipid A elicited titers of 1:5,000 of anti-Abeta(1-16) antibodies within 10 weeks after the first inoculation. On direct interaction, sera with antibody titers of 1:5,000 solubilized in vitro up to 80% of preformed Abeta(1-42) aggregates. Cryosections of pancreases of unvaccinated NORBA mice show, on staining with Thioflavin T, extensive areas of high-intensity fluorescence in the acinar cell fields. Quantitation of the average fluorescence intensity in each section indicated that: (i) whereas nonvaccinated NORBA mice develop plaques within 45-60 days after birth, vaccinated 8-week-old NORBA mice did not develop amyloid plaques on their pancreases over a period of 7 months; (ii) cryosections from pancreases of 9- and 15-month-old vaccinated NORBA mice showed less than 50% of the fluorescence shown by cryosections from unvaccinated animals of the same age. The results indicate that palmitoylated Abeta peptides, reconstituted in liposomes-lipid A, are highly immunogenic, eliciting "therapeutic" antibody titers within 3 months of the first inoculation and preventing amyloid plaque formation in young animals or significantly reducing existing plaques in older transgenic mice. Possible implications for the therapy of Alzheimer's disease are discussed.

Alzheimer Disease↗

PubMed2002

Risk factors for Helicobacter pylori resistance in the United States: the surveillance of H. pylori antimicrobial resistance partnership (SHARP) study, 1993-1999.

BACKGROUND: Pretreatment antimicrobial resistance has an important impact on the efficacy of many Helicobacter pylori treatment regimens. OBJECTIVE: To estimate the prevalence of H. pylori resistance to antimicrobials in the United States, to characterize risk factors associated with H. pylori antimicrobial resistance, and to explore the association between drug utilization and antimicrobial resistance patterns over time. DESIGN: Meta-analysis using patient-level data. SETTING: 20 nationwide trials of H. pylori eradication. PATIENTS: 3624 men and women, each of whom contributed one isolate. MEASUREMENTS: Rates of H. pylori resistance to clarithromycin, metronidazole, and amoxicillin, according to geographic region, age, sex, study year, ethnicity, ulcer status, test method, and study. RESULTS: Overall resistance to clarithromycin, metronidazole, and amoxicillin was 10.1% (95% CI, 9.1% to 11.1% [360 of 3571 patients]), 36.9% (CI, 35.1% to 38.7% [1063 of 2883 patients]), and 1.4% (CI, 1.0% to 1.8% [48 of 3486 patients]), respectively. In multivariable analyses, multiple risk factors were associated with resistance to individual agents. Clarithromycin resistance was significantly associated with geographic region (P = 0.050), older age (P < 0.001), female sex (P < 0.001), inactive ulcer disease (P < 0.001), and study (P = 0.010). Metronidazole resistance was significantly associated with female sex (P < 0.001), earlier year of study enrollment (P = 0.036), Asian ethnicity (P < 0.001), use of an epsilometer test (P = 0.002), and study (P < 0.001). Amoxicillin resistance was low and was not significantly associated with any risk factor. In the 1990s, when rates for use of oral macrolides and metronidazole were relatively stable, clarithromycin resistance rates were stable and metronidazole resistance rates varied. CONCLUSIONS: Clinicians should consider risk factors for antimicrobial resistance when deciding which patients should have susceptibility testing and when choosing appropriate H. pylori treatments in the empirical setting.

Adolescent↗

PubMedDate not supplied

Safety and immunogenicity of new cell-cultured smallpox vaccine compared with calf-lymph derived vaccine: a blind, single-centre, randomised controlled trial.

BACKGROUND: US government organisations have identified the need for a new smallpox vaccine to replenish limited stocks of the approved, calf-lymph derived vaccine, the manufacture of which is no longer acceptable. We aimed to compare the safety and immunogenicity of the new cell-cultured smallpox vaccine (CCSV) to that of the calf-lymph derived vaccine (as a positive control) in 350 healthy, adult volunteers. METHODS: We did a randomised controlled study at the University of Kentucky Medical Center. We randomised 150 vaccinia-naive volunteers, aged 18-30 years, and 100 vaccinia-non-naive people, aged 32-65 years, to equivalent doses of either CCSV or test vaccine (2.5x10(5) plaque-forming units) by 15 puncture scarification in double-blind fashion. Immunogenicity was assessed by pock formation (take rate), humoral immune response by plaque-reduction neutralisation titres, and cellular immune response by vaccinia-specific, interferon-gamma T-cell quantification, cytotoxicity, and T-cell proliferation response. A further 100 vaccine-naive individuals, aged 18-30 years, received one of five doses of CCSV (undiluted, diluted 1 in 5, 1 in 10, 1 in 25, and 1 in 50) in single-blind fashion. Routine laboratory assessments, physical examinations, and recording of adverse events were done to assess vaccine safety. The primary endpoints were safety and reactogenicity (take rate) of CCSV. FINDINGS: 349 (99.7%) of 350 volunteers developed pock lesions; one vaccinia-naive individual who received a 1 in 25 dilution of CCSV did not. The rate of adverse events related to vaccine and the extent of humoral and cellular immune responses did not differ between the vaccine groups in vaccinia-naive or non-naive people. CCSV was immunogenic in vaccine-naive volunteers at a dose 50 times lower than that approved for Dryvax. INTERPRETATION: CCSV seems to be a safe and immunogenic alternative to calf-lymph derived vaccine for both vaccinia-naive and non-naive people.

Adolescent↗