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Biomedical subjects

M J England

Publications and source records attributed to M J England.

At least 19 recordsLinked to original sources
PubMed1997

Time of peak drug concentration after a single dose and a dose at steady state.

The time of peak concentration after administration of oral drug is an often quoted and used pharmacokinetic parameter. It is not well appreciated, however, that the peak times after a single dose and a dose at steady state during a multiple administration regimen can differ significantly. This article derives the mathematical relationships that determine how a peak time at steady state differs from that after a single or first dose. These relationships are then evaluated using three different approaches: 1) graphic simulations of time courses of drug concentration for three hypothetical drugs; 2) comparisons of predicted and observed peak times using examples from the literature; and 3) comparisons of predicted and simulated peak times based on different sampling schedules for three hypothetical drugs. The key finding is that peak times after a dose at steady state can occur considerably earlier after administration than after a single dose. However, the manner by which peak times are usually determined, that is, the sampling time corresponding to the highest measured drug concentration, imposes significant limitations on the usefulness of this parameter.

Administration, Oral↗
PubMed1997

Comparative efficacy of a Coxiella burnetii chloroform:methanol residue (CMR) vaccine and a licensed cellular vaccine (Q-Vax) in rodents challenged by aerosol.

Q fever is an acute and self-limited febrile illness caused by the obligate intracellular bacterium Coxiella burnetii. While phase I cellular Q fever vaccines are efficacious in humans, vaccination of immune individuals may result in sterile abscesses and granulomas. The chloroform:methanol residue vaccine (CMR) was developed as a safer alternative. The efficacy of a licensed phase I cellular vaccine (Q-Vax) was compared with that of CMR vaccine in A/J mice and Hartley guinea pigs challenged with virulent phase I C. burnetii by aerosol. Both vaccines were efficacious. The CMR vaccine dose required to protect 50% of mice (PD50) against lethal aerosol challenge (11 LD50) was one-third of the Q-Vax dose. However, the PD50 for CMR was four times the Q-Vax dose in guinea pigs challenged by aerosol (60 LD50). It was concluded that CMR is an efficacious alternative to cellular Q fever vaccines for the prevention of Q fever.

Aerosols↗
PubMed1997

Women and managed care.

The nation's health care system is undergoing a period of rapid change that will profoundly affect women's health care services and, ultimately, women's health. Although managed care is quickly becoming the predominant mode of health care delivery in the United States, a new, more consumer-focused, and accountable model known as organized systems of care (OSC) is emerging. OSC development has been driven by large private and public employers seeking to purchase the highest quality health care for the best price. The changes in health care delivery encouraged by these innovative employers will provide women with optimal care and attention, which will in turn help them attract and retain a competitive and productive workforce.

Female↗
PubMed1996

Immunogenicity of a new lot of Francisella tularensis live vaccine strain in human volunteers.

A new lot of Francisella tularensis live vaccine strain (LVS) was tested for immunogenicity in 19 human volunteers. Scarification vaccination induced specific cell-mediated and humoral immune responses. We noted a significant rise in antibodies against irradiation-killed LVS, formalin-killed virulent strain SCHU4, and an ether extracted antigen preparation (EEx) beginning 14 days after vaccination. A main target of the humoral immune response was lipopolysaccharide. Eighty percent of vaccinated volunteers developed a positive IgG response to EEx by day 14 and 100% of vaccinees responded positively by day 21. Background IgA titers were lower than corresponding IgG or IgM titers. No early IgM rise was noted with any antigen. By day 14 after vaccination, in vitro lymphocyte responses to LVS, the rough variant of LVS, and EEx were significantly increased compared to controls. Seventy percent of volunteers had a positive in vitro lymphocyte response to EEx within 14 days of vaccination. We predict that EEx will be a useful antigen for diagnosing tularemia and for evaluating the immunogenicity of vaccines against tularemia. We are testing this antigen using sera from human cases of tularemia and control sera.

Antibodies, Bacterial↗
PubMed1995

Cell-mediated and humoral immune responses after vaccination of human volunteers with the live vaccine strain of Francisella tularensis.

The specific humoral and cell-mediated immune responses of human volunteers vaccinated with the Francisella tularensis live vaccine strain (LVS) were evaluated. In the search for an optimal antigen to measure the immunogenicity of the vaccine in an enzyme-linked immunosorbent assay, we tested irradiation-killed LVS, an aqueous ether extract of the LVS (EEx), lipopolysaccharide (LPS) from LVS, and a virulent strain (SCHU4). Volunteers were immunized with LVS by scarification. Immunoglobulin G (IgG) responses to LVS and LPS gave the highest background titers when tested with sera from unimmunized volunteers, whereas IgA, IgG, and IgM background titers to EEx and SCHU4 were low. Vaccination caused a significant rise (P < 0.01) in IgA, IgG, and IgM titers to all antigens tested, except for the IgG response to LPS. Eighty percent of vaccinated volunteers developed a positive IgG response to EEx 14 days postvaccination, while 50% were positive to LVS. By day 14 after vaccination, 70% of immunized volunteers exhibited a positive response to EEx in an in vitro peripheral blood lymphocyte proliferation assay. EEx, a specific and sensitive antigen for evaluating immune responses of vaccinated volunteers, may be a superior antigen for the diagnosis of tularemia.

Adolescent↗
PubMed1994

Estimation of pharmacokinetic parameters for simulations of time courses of drug concentrations after oral administration.

Simulations of time courses of drug concentrations after oral administration are frequently hampered by the lack of pharmacokinetic parameters after oral dosing. This article presents methods by which to estimate such parameters from pharmacokinetic parameters after intravenous dosing and knowledge of time of peak concentration and bioavailability after oral dosing. The application of these approaches enables the generation of meaningful graphic simulations of time courses of drug concentrations after oral administration that can have educational and illustrative uses.

Absorption↗
PubMed1992

Vaccines against coxiellosis and Q fever. Development of a chloroform:methanol residue subunit of phase I Coxiella burnetti for the immunization of animals.

We have demonstrated the safety, immunogenicity, and efficacy of the WC and CMR vaccines in guinea pigs. Vaccination of guinea pigs with either WC or CMR protects animals against challenge with virulent C. burnetii. A total of 2 micrograms of either WC or CMR vaccine was a significant priming dose. A total of 20 micrograms gave complete protection against lethal challenge. Detection of antibodies to phase II cells by microaglutination, after vaccination with either WC or CMR and before lethal challenge, correlated with the ability of guinea pigs to mount a protective immune response. The PD50 values for WC and CMR vaccines, administered as a single dose, were 0.3 and 1.4 micrograms per animal, respectively. In contrast, the PD50 values for the WC and CMR vaccines, administered as two doses, were 0.83 and 0.72 micrograms per animal, respectively. Although the PD50 values for the two vaccines are similar, the CMR vaccine is preferred over the WC vaccine because it induces significantly fewer adverse reactions, and repeat injections can be given. Unvaccinated guinea pigs do not clear infectious microorganisms after challenge infection. Vaccination before challenge infection reduces the infectious load of C. burnetti in the blood and in various organs of the animals. When vaccinated animals were challenge infected and treated with rifampicin, the microorganisms were not eliminated from various organs. However, the combination of vaccination, challenge, and rifampicin treatment is effective in reducing the number of infectious microorganisms in some of these sites. We have demonstrated the safety and immunogenicity of the CMR vaccine in sheep and goats. Animals that were seropositive for one or more antigens developed significant levels of antibodies to alternate antigens, but no adverse reactions were observed at the site of s.c. injection of the CMR vaccine. This demonstrates that seropositive animals can be successfully immunized with this vaccine. These results also indicate that a long-term vaccination program using the CMR vaccine has the potential for producing animals with significant antibody titers to C. burnetii and perhaps lifelong immunity. The goal of a Q fever vaccination program is to produce immunized animals that are able to clear completely the infectious microorganisms. The appropriate vaccination schedule to render adult animals and their offspring "Q fever-free" should now be thoroughly investigated.

Animals↗
PubMed1992

Cell-mediated and humoral immune responses induced by scarification vaccination of human volunteers with a new lot of the live vaccine strain of Francisella tularensis.

Tularemia is a disease caused by the facultative intracellular bacterium Francisella tularensis. We evaluated a new lot of live F. tularensis vaccine for its immunogenicity in human volunteers. Scarification vaccination induced humoral and cell-mediated immune responses. Indications of a positive immune response after vaccination included an increase in specific antibody levels, which were measured by enzyme-linked immunosorbent and immunoblot assays, and the ability of peripheral blood lymphocytes to respond to whole F. tularensis bacteria as recall antigens. Vaccination caused a significant rise (P less than 0.05) in immunoglobulin A (IgA), IgG, and IgM titers. Lymphocyte stimulation indices were significantly increased (P less than 0.01) in vaccinees 14 days after vaccination. These data verify that this new lot of live F. tularensis vaccine is immunogenic.

Antibody Formation↗
PubMed1992

Building systems of care for youth with serious mental illness.

In 1990 the Robert Wood Johnson Foundation's Mental Health Services Program for Youth awarded grants to eight state-community partnerships to develop systems of care for mentally ill children and adolescents. The authors describe approaches to system building in the program's first two years of implementation. The evolving systems consist of government agencies in child welfare, mental health, public health, education, and juvenile justice, as well as private-sector health and mental health care providers. Basic system features include interagency steering committees and long-term intensive case management. Fundamental principles guiding system development are individualization of care to meet the needs of the specific child, organization of care to empower families to manage care over the long term, flexible financing of care, and normalization of care in family and community settings.

Adolescent↗
PubMed1990

The effect of magnesium sulphate infusion on circulating catecholamine levels in severe gestational proteinuric hypertension. A report of 8 cases.

The effect of magnesium sulphate (MgSO4) infusion on blood pressure and circulating venous catecholamine levels in 8 patients with severe gestational proteinuric hypertension is described. A significant fall in blood pressure was noted after MgSO4 infusion; the maximal fall in diastolic blood pressure correlated with the greatest rise in serum magnesium levels (P less than 0.04). No significant change was observed in mean venous plasma adrenaline or noradrenaline levels after MgSO4 infusion, although the mean dopamine concentration declined significantly. It is concluded that the decrease in systemic vascular resistance after MgSO4 infusion in gestational proteinuric hypertension is mediated predominantly by mechanisms other than a change in circulating catecholamine levels.

Adult↗