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Biomedical subjects

E Miller

Publications and source records attributed to E Miller.

At least 181 records · Page 10Linked to original sources
PubMed1996

The effect of an accelerated immunisation schedule on pertussis in England and Wales.

Notifications of pertussis in England and Wales have fallen dramatically from 65 810 during the epidemic year of 1982 to 3963 cases during the epidemic year of 1994, as vaccine coverage has risen. The incidence of pertussis has declined in all ages, including babies under 3 months of age who would have been at risk of disease from older siblings vaccinated under the accelerated schedule introduced in 1990 if immunity induced as result of this schedule had been short lived. To document the efficacy of the current whole cell vaccine under the accelerated schedule an enhanced surveillance scheme based on laboratory confirmed cases of pertussis was set up in 1994. Three deaths occurred in infants with confirmed pertussis, all of whom were under 8 weeks of age and unvaccinated. The overall vaccine efficacy for those over 6 months and under 5 years of age was 94%. This estimate may be inflated, as a number of biases could lead to the underascertainment of cases in vaccinated children, but it is similar to previous estimates obtained for children of the same age vaccinated under the 3, 5, and 10 month schedule. Vaccine efficacy was 89% for children aged over 5 and under 15 years. The enhanced surveillance scheme will enable us to monitor the duration of protection under the accelerated schedule and evaluate the continuing impact of pertussis infection.

Adolescent↗
PubMed1996

Studies on tetrachloroethene respiration in Dehalospirillum multivorans.

Tetrachloroethene (PCE) respiration was studied in the tetrachloroethene-utilizing anaerobe, Dehalospirillum multivorans, with respect to localization of the catabolic enzymes, the electron carriers potentially involved in electron transport, and the response to ionophores and specific inhibitors. Hydrogenase and formate dehydrogenase were recovered in the periplasmic cell fraction and were membrane-associated. Electron-accepting tetrachloroethene dehalogenase was found in the cytoplasmic fraction. In the PCE dehalogenase assay, only artificial electron donors with a standard redox potential of D. multivorans (Eo' = -445 mV) could serve as electron donor for PCE reduction. However, the reaction rate with ferredoxin was only 1% of that with methyl viologen, whereas the pyruvate-ferredoxin oxidoreductase exhibited almost the same reaction rates with methyl viologen and ferredoxin as electron acceptors for pyruvate oxidation. Reduced menadione (2-methyl-1, 4-naphthoquinone) did not serve as electron donor in the PCE dehalogenase reaction. 2-Heptyl-4-hydroxyquinoline-N-oxide (HOQNO) had no significant effect on PCE dechlorination in cell suspensions and in crude extracts. Whole cells catalyzed the reductive dechlorination of PCE with H2 or formate as electron donors. The dechlorination in cell suspensions rather than in cell extracts was inhibited by the ionophores carbonylcyanide-p-(trifluoromethoxy)phenylhydrazone (FCCP) and tetrachlorosalicylanilide (TCS), indicating that a membrane potential and/or a pH gradient may be required for the reaction in vivo.

Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone↗
PubMed1996

Lea's Shield: a study of the safety and efficacy of a new vaginal barrier contraceptive used with and without spermicide.

The purpose of this study was to evaluate the safety, efficacy and acceptability of Lea's Shield, a new vaginal contraceptive barrier device, when used with either spermicidal or non-spermicidal lubricant. One-hundred-eighty-five (185) women enrolled at six centers. Half were randomized to use the device with spermicide and half with a non-spermicidal lubricant. To be eligible, volunteers had to be 18-40 years old (inclusive), in good health with regular menses, sexually active in an ongoing relationship and at risk for pregnancy, and willing to use Lea's Shield as their sole means of contraception for six months. Participants were seen at admission, one week, one month, three months and six months. Gross cumulative life table rates were calculated for pregnancy and others reasons for discontinuation. Adverse experiences and responses to an acceptability questionnaire were evaluated. One-hundred-eighty-two (182) volunteers contributed data to the analysis of safety and 146 to that of contraceptive efficacy. The unadjusted six-month life table pregnancy rate was 8.7 per 100 women for spermicide users and 12.9 for non-spermicide users (p = 0.287). After controlling for age, center, and frequent prior use of barrier methods, the adjusted six-month life table pregnancy rate was 5.6 for spermicide users and 9.3 for non-spermicide users (p = 0.086), indicating that use of spermicide lowered pregnancy rates, although not significantly, during typical use. For purposes of comparison, it is important to note that this study differed from the cap/diaphragm and sponge/ diaphragm studies in that a high percentage (84%) of volunteers were parous. For reasons that are unclear, pregnancy rates among parous women using barrier contraceptives tend to be higher than among nulliparous women. Indeed, in this study there were no pregnancies among nulliparous users of Lea's Shield. Standardization of parity of this study population on those of the cap/diaphragm and sponge/diaphragm studies suggests that unadjusted pregnancy rates for this device would have been considerably lower (2.2 and 2.9 per 100 users of spermicide and non-spermicide, respectively) had the study been done using the populations of earlier studies. Since no directly comparative study has been done, these figures provide a tentative estimate of the relative efficacy of Lea's Shield compared with the sponge, cap, and diaphragm. There were no serious adverse experiences attributed to the use of Lea's Shield. Acceptability was very good. Seventy-five percent (75%) of women responded to an end-of-study questionnaire; 87% of these reported that they would recommend Lea's Shield to a friend. Lea's Shield is a new vaginal contraceptive that does not require clinician fitting. Pregnancy rates in this study compare favorably with other studies of barrier contraceptive methods including the cervical cap, diaphragm, and sponge, even though this study was done with greater rigor and with a greater percentage of parous women than previous barrier studies. Lea's Shield appears to be safe and very acceptable to study volunteers.

Adult↗
PubMed1996

Measles immunity and response to revaccination among secondary school children in Cumbria.

The prevalence of antibody to measles virus in 759 children aged 11-18 years attending a secondary school in Cumbria was measured using a salivary IgG antibody capture assay. Serum IgG antibody levels were measured using a plaque reduction neutralization assay in subjects whose saliva was antibody negative. Vaccination histories were obtained from the child health computer and general practice record. A total of 662 pupils (87% of those tested) had detectable measles-specific IgG in saliva. Of the remaining 97, 82 provided blood samples and 29 had serum neutralizing antibody levels above 200 mIU/ml. Afer adjusting for non-participation rates, the proportion considered non-immune (no IgG in saliva and < or = 200 mIU/ml in serum) was 9% overall, ranging from 6% in vaccinated children to 20% in unvaccinated children. Measles-mumps-rubella vaccine was given to 50 children of whom 38 provided post-vaccination serum and 32 saliva samples. Thirty (79%) had a fourfold or greater rise in serum neutralizing antibody and 28 (88%) developed IgG antibody in saliva. Half of the children considered non-immune by antibody testing would have been overlooked in a selective vaccination programme targeted at those without a history of prior vaccination. A programme targeted at all school children should substantially reduce the proportion non-immune since a primary or booster response was achieved in three quarters of previously vaccinated children with low antibody levels and in all unvaccinated children. While it is feasible to screen a school-sized population for immunity to measles relatively quickly using a salivary IgG assay, a simple inexpensive field assay would need to be developed before salivary screening and selective vaccination could substitute for universal vaccination of populations at risk of measles outbreaks. The salivary IgG assay provided a sensitive measure of a booster response to vaccination.

Adolescent↗
PubMed1996

Intermediate-dose busulphan before autografting for advanced-phase chronic myeloid leukaemia.

Between June 1994 and October 1995 we performed 11 autografts in nine patients with advanced-phase chronic myeloid leukaemia (CML) using an attenuated cytoreductive regimen consisting of busulphan 8 mg/kg given in divided doses over 4 d. Five patients were restored to chronic phase. Four patients survived > 50 weeks and one remains well at 79 weeks. Toxicity was generally mild. Four procedures were managed entirely in the out-patient clinic. Therefore autografting after this 'intermediate' dose busulphan provides good palliation for patients with advanced CML with relatively little toxicity. Attenuated autografting should offer major advantages in terms of quality of life and cost for patients with advanced-phase CML.

Adult↗
PubMed1996

Varicella-zoster virus epidemiology--a changing scene?

Chickenpox is a relatively mild disease in healthy children but may be life threatening in immuno-suppressed patents, neonates, and normal adults, especially smokers-for whom the risk of varicella pneumonia is high. The epidemiology of chickenpox appears to be changing: There has been an unexplained upward shift in the age distribution of cases over the last 20 years. This is reflected by increased consultations for chickenpox in general practices and more deaths in England and Wales. On the basis of hospital admissions for chickenpox in young adults, there is evidence of a similar trend in the United States. This epidemiologic change has important consequences for future mortality rates and for risk of infection in health care workers and pregnant women. The potential use of the varicella vaccine should be considered as a measure to reduce the risk of nosocomial transmission in view of the possible changing epidemiology of varicella.

Adolescent↗
PubMed1996

What changes drug metabolism in critically ill patients?--II Serum inhibits the metabolism of midazolam in human microsomes.

Serum samples from five critically ill patients were incubated with microsomes prepared from three human livers. The activity of cytochrome P450 3A4 was assessed by measuring the disappearance of midazolam and the appearance of 1-hydroxy midazolam in the incubates. Significant inhibition of the ability of this enzyme to metabolise midazolam was seen. This occurred in incubates containing serum samples from critically ill patients and not in those containing serum from two normal volunteers. The mechanism of this inhibition is unknown, but several possibilities are discussed.

Aged↗
PubMed1996

What changes drug metabolism in critically ill patients--III? Effect of pre-existing disease on the metabolism of midazolam.

Liver samples were obtained at hepatectomy from patients with end stage alcoholic liver disease (n = 5), primary biliary cirrhosis (n = 5) and chronic rejection needing retransplantation (n = 5). Normal liver material was also obtained from five organ donors. From these samples microsomes were made containing cytochrome P450 3A. The amount of this enzyme was measured by Western immunoblotting and its function assessed by measuring the rate of production of two metabolites of midazolam, 1-hydroxy midazolam and 4-hydroxy midazolam. There was a wide range in all groups for both the expression and function of this enzyme. Liver tissue affected by cirrhotic disease showed greater preservation of enzyme function than that affected by hepatocellular disease. There was a good correlation between the expression of the enzyme and production of the 1-hydroxy metabolite, but a poor correlation between production of the 4-hydroxy metabolite and expression. This poor correlation may reflect the failure to measure the specific enzyme responsible for producing 4-hydroxy midazolam.

Adult↗
PubMed1996

The Drosophila Polycomb group gene Sex comb on midleg (Scm) encodes a zinc finger protein with similarity to polyhomeotic protein.

The Sex comb on midleg (Scm) gene is a member of the Polycomb group (PcG) of genes in Drosophila melanogaster. The PcG genes encode transcriptional repressors required for proper spatial expression of homeotic genes. We report the isolation of new Scm mutations and the molecular characterization of the Scm gene. Scm mRNA is expressed maternally, at peak levels in early embryos and then at lower levels throughout the remainder of development. Scm encodes a putative zinc finger protein of 877 amino acids. Scm protein is similar to polyhomeotic, another member of the PcG, both in the zinc finger region and in a separate C-terminal domain of 60 amino acids, which we term the SPM domain. Sequence analysis of an Scm mutant allele suggests a functional requirement for the SPM domain. Scm protein also bears homology in multiple domains to a mouse protein, Rae-28 (Nomura, M., Takihara, Y. and Shimada, K. (1994) Differentiation 57,39-50) and to a fly tumor suppressor protein, the product of the lethal(3)malignant brain tumor gene (Wismar, J. et al., (1995) Mech. Dev. 53, 141-154). Possible functional relationships among these proteins and potential biochemical roles for Scm protein in PcG repression are discussed.

Amino Acid Sequence↗
PubMed1996

von Willebrand factor in diabetic retinopathy.

OBJECTIVE: To elucidate the qualitative nature of elevated levels of von Willebrand factor (vWF) in diabetic microagiopathy. DESIGN: A randomized controlled study. SETTING: Oxford Health Authority, Oxfordshire, United Kingdom. SUBJECTS: Insulin dependent diabetic patients with established retinopathy, and an age, sex matched control group. MAIN OUTCOME MEASURES: Diabetic retinopathy, a modified enzyme-linked immunosorbent assay (ELISA), used to distinguish between endothelial and plasma type vWF. RESULTS: vWF is higher in patients with diabetic retinopathy mean (217u/dl) compared with normal subjects mean (8/u/dl). vWF in both patient and control are of the plasma type. CONCLUSION: vWF in diabetic retinopathy is raised and of the plasma type, suggesting it is not due to acute vascular endothelial injury.

Case-Control Studies↗
PubMed1995

Observational study of effect of intrauterine transfusions on outcome of fetal hydrops after parvovirus B19 infection.

The role of intrauterine transfusion for fetal hydrops arising from maternal paravirus B19 infection is unclear. 66 cases of fetal hydrops arising from B19 infection were reported in England and Wales between June, 1992, and September, 1994. In 29 cases the fetus was dead at the time of the first abnormal ultrasound or a therapeutic abortion as performed; 12 of the 38 alive at the first abnormal scan received intrauterine transfusions and 3 of the 12 died. 26 did not receive intrauterine transfusions and 13 died. After adjustment for the severity of the hydrops as assessed by the ultrasound and for gestational age, the odds of death among those who received an intrauterine transfusion was significantly less than among those who did not (odds ratio 0.14, 95% CI 0.02-0.96). These findings suggest that intrauterine transfusion will benefit some fetuses with hydrops arising from parvovirus B19 infection.

Adult↗