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M J England

Publications and source records attributed to M J England.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

Maternal and fetal sequelae of anticoagulation during pregnancy in patients with mechanical heart valve prostheses.

Previous reports indicate an increased risk of thrombotic and embolic events in patients with mechanical heart valve prostheses during pregnancy. We prospectively followed 50 pregnancies in 49 patients with 62 cardiac prostheses from presentation at the antenatal clinic through the remainder of the pregnancy. Of the 60 mechanical prostheses, 39 were Medtronic-Hall, 7 St. Jude Medical, 7 Starr-Edwards and 7 Björk-Shiley. Forty-three patients were in New York Heart Association functional class I or II and 6 were in functional class III or IV. Forty-five patients were in sinus rhythm and 4 had chronic atrial fibrillation. All patients received warfarin during the first and second trimesters. Forty-one pregnancies proceeded beyond 28 weeks. In 23 of these (group I) warfarin was replaced with heparin at 36 weeks gestation. In the remaining 18 (group II) warfarin was not substituted owing to premature onset of labor. The target prothrombin ratio (international normalized ratio) in patients receiving warfarin was 2.0 to 2.5. The partial thromboplastin time was maintained at 1.5 to 2.5 times the control value in patients receiving heparin. Eleven patients received dipyridamole plus warfarin for the duration of pregnancy. There were no maternal thromboembolic complications or deaths associated with pregnancy. Antepartum hemorrhage occurred in 1 patient at 35 weeks gestation. One patient (group I) experienced peripartum hemorrhage. All patients were hemodynamically stable before delivery, but 2 developed pulmonary edema during labor. The mean fetal birth weight was low (2.54 +/- 0.98 kg). There were 9 abortions (18%), 7 stillbirths (14%), 2 neonatal deaths (4%) and 2 instances of warfarin embryopathy (4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Transient postpartum amaurosis. A report of four cases.

The association between amaurosis and preeclampsia has been extensively documented of late. In four women with amaurosis, the major etiologic factor appeared to be dramatic fluctuations in blood pressure associated with an excessive peripartum blood loss. One patient was found to have an area of cortical infarction, as evidenced by computed tomography. All four patients made a full recovery.

Adult

Suppression of lactation. A comparison of bromocriptine and prostaglandin E2.

Women in the puerperium who requested lactation suppression were randomly allocated to receive bromocriptine from puerperal day 1 to 14 or prostaglandin E2 from day 3 or 4 for 24 hours. Subjectively, lactation suppression was satisfactory in all cases. Objective measurements showed a trend toward more-effective early suppression with bromocriptine. After discharge from the hospital, 3 of the 21 women who received prostaglandin E2 complained of mild breast tenderness, whereas 10 of the 22 who received bromocriptine reported severe "rebound" breast tenderness.

Bromocriptine

Tick-bite fever in pregnancy. A case report.

Despite the frequency of tick-bite fever in southern Africa and its doubtless occurrence in pregnancy, this report documents the first case in a pregnant woman. Consequently, the natural history of tick-bite fever in pregnancy and concomitant placental involvement must be regarded as conjectural. Accordingly a register has been opened by the Department of Obstetrics and Gynaecology, University of the Witwatersrand, for recording similar cases. At this stage of our knowledge, erythromycin 500 mg 6-hourly until 3-5 days after defervescence is the therapy of choice for such patients.

Adult

Pregnancy induced hypertension: will treatment with dietary eicosapentaenoic acid be effective?

The current understanding of endothelial membrane prostaglandin metabolism is presented together with an explanation of how this may be altered in pregnancy induced hypertension (PIH). A hypothesis is proposed to explain why dietary supplementation with eicosapentaenoic acid (EPA) may reverse abnormal prostaglandin metabolism, increase membrane fluidity and lower blood pressure in PIH.

Eicosapentaenoic Acid

Epithelial ovarian tumours of low malignant potential.

The available literature and the management of epithelial tumours of low malignant potential (LMP) is reviewed. The criteria for a diagnosis of LMP at the University of the Witwatersrand are delineated in detail. Based on the records in the Ovarian Tumour Registry of this University, experience with 29 such tumours over 4 years is presented. Of these, 14 (48.3%) were of the serous variety, 12 were mucinous (41.4%), and 2 (6.9%) were mucinous-serous, the remaining 1 (3.4%) being endometrioid. LMP tumours accounted for 12.9% of proliferating epithelial ovarian tumours in black patients compared with 16.9% in white patients. Pelviperitoneal cytological washings for detection of malignant cells in patients with LMP tumours is mandatory.

Adult