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1.  Transmission of GB Virus Type C via Transfusion in a Cohort of HIV-Infected Patients 
The Journal of Infectious Diseases  2012;205(9):1436-1442.
Background. GB virus C (GBV-C) infection is transmitted by blood exposure and associated with lower human immunodeficiency virus (HIV) load and slower HIV disease progression. Few studies describe predictors of acute GBV-C infection following transfusion in HIV-infected patients.
Methods. We used a limited-access database from the National Heart Lung and Blood Institute’s Viral Activation Transfusion Study, a randomized controlled trial of leukoreduced versus nonleukoreduced transfusions received by HIV-infected, transfusion-naive patients. Blood samples from 489 subjects were tested for GBV-C markers in pretransfusion and posttransfusion samples. We estimated the risk of acquiring GBV-C RNA and predictors of GBV-C acquisition, using pooled logistic regression.
Results. GBV-C RNA was detected ≤120 days following the first transfusion in 22 (7.5%) of 294 subjects who were GBV-C negative before transfusion. The risk of GBV-C RNA acquisition increased with each unit transfused (odds ratio, 1.09; 95% confidence interval, 1.06–1.11). Lower baseline HIV load and use of antiretroviral therapy were associated with subsequent GBV-C RNA acquisition, after control for units of blood transfused. Leukoreduced status of transfused units was not associated with GBV-C transmission.
Conclusions. Blood transfusion is associated with a significant risk of GBV-C acquisition among HIV-infected patients. Transmission of GBV-C by blood transfusion was inversely related to HIV load.
PMCID: PMC3324396  PMID: 22438325
2.  GB virus C infection among young, HIV-negative injection drug users with and without hepatitis C virus infection 
Journal of viral hepatitis  2011;18(4):e153-e159.
Our study examined the association between GB virus C (GBV-C) and (i) hepatitis C virus (HCV) infection status, (ii) biomedical indicators of liver disease (alanine and aspartate aminotransferases) and (iii) HCV RNA level among young injection drug users (IDUs) recruited using street outreach and respondent-driven methods. Cross-sectional and longitudinal analyses were completed. GBV-C (active or resolved) infection was significantly (P < 0.05) more prevalent among HCV antibody-positive (anti-HCV+) (65.1%) than antibody-negative (anti-HCV–) (32.3%) (OR = 3.9, 95% CI: 2.3–6.9) IDUs. The prevalence of resolved GBV-C infection was highest among those with chronic HCV infection (41.9%), followed by those with resolved HCV infection (34.4%) and significantly lower (P < 0.05) among anti-HCV participants (16.9%). Although not statistically significant (P = 0.13), a similar pattern was observed for active GBV-C infection. No association between GBV-C infection status and biomedical indicators of liver disease or HCV RNA level over time was observed. In conclusion, GBV-C infection prevalence was higher among anti-HCV+ compared to anti-HCV– young IDUs, similar to prior studies among older populations. In particular, chronically HCV-infected young IDUs had an increased rate of GBV-C clearance.
PMCID: PMC3543827  PMID: 20738773
co-infection; GB virus C; hepatitis C virus; injection drug users; prevalence
3.  Establishment of a New Human Pneumococcal Standard Reference Serum, 007sp ▿ 
Clinical and Vaccine Immunology : CVI  2011;18(10):1728-1736.
Lot 89SF has been the reference standard serum pool used in pneumococcal enzyme-linked immunosorbent assays (ELISAs) since 1990. In 2005, it was estimated that there remained between 2 and 5 years' supply of lot 89SF. Since lot 89SF was the reference standard used in the evaluation of the seven-valent pneumococcal conjugate vaccine Prevnar (PCV7), the link to clinical efficacy would be severed if stocks became completely depleted. Furthermore, demonstration of immune responses comparable to those elicited by PCV7 is a licensure approach used for new pneumococcal conjugate vaccines, so a replacement reference standard was required. A total of 278 volunteers were immunized with the 23-valent unconjugated polysaccharide vaccine Pneumovax II, and a unit of blood was obtained twice within 120 days following immunization. Plasma was prepared, pooled, and confirmed to be free from hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV. The pooled serum was poured at 6 ml per vial into 15,333 vials and lyophilized. Immunological bridging of 007sp to 89SF was used to establish equivalent reference values for 13 pneumococcal capsular serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) by five independent laboratories. Antibody concentrations in 007sp were established relative to the lot 89SF reference preparation using the WHO reference ELISA. Subsequently, 12 existing WHO calibration sera had concentrations reassigned for 13 pneumococcal serotypes using new serum 007sp as the reference, and these were compared to concentrations relative to the original reference serum. Agreement was excellent for the 12 WHO calibration sera. The 007sp preparation has replaced 89SF as the pneumococcal reference standard. Sufficient quantity of this new preparation is available such that, with judicious use, it should be available for at least 25 years.
PMCID: PMC3187044  PMID: 21852547
5.  Effect of Primer Selection on Estimates of GB Virus C (GBV-C) Prevalence and Response to Antiretroviral Therapy for Optimal Testing for GBV-C Viremia 
Journal of Clinical Microbiology  2006;44(9):3105-3113.
GB virus C (GBV-C; also called hepatitis G virus) is a common cause of infection associated with prolonged survival among HIV-infected individuals. The prevalences of GBV-C viremia vary widely in different studies, and there has been poor agreement among different laboratories performing GBV-C RNA detection in quality control studies. To determine the optimal method of measuring GBV-C RNA in clinical samples, samples obtained from 939 HIV-infected subjects were studied using reverse transcription (RT)-PCR methods amplifying four separate regions of the GBV-C genome. Primers amplifying the E2 coding region were 100% specific; however, their sensitivity was only 76.6%. In contrast, primers amplifying three additional conserved regions of the GBV-C genome (the 5′ nontranslated region and the nonstructural protein-coding regions 3 and 5A) were more sensitive but produced higher rates of false-positive results. Using low-specificity primer sets influenced the significance of association between GBV-C viremia and response to antiretroviral therapy. Using a quantitative GBV-C RNA method, the GBV-C RNA concentration did not correlate with baseline or set point HIV RNA levels; however, a correlation between negative, low, and high GBV-C RNA levels and increasing reduction in HIV RNA following antiretroviral therapy was observed. Subjects with both GBV-C E2 antibody and viremia had significantly lower GBV-C RNA levels than did viremic subjects without E2 antibody. These studies demonstrate that accurate detection of GBV-C RNA by nested RT-PCR requires the use of primers representing multiple genome regions. Analyses based on testing with single primers do not lead to reliable conclusions about the association between GBV-C infection and clinical outcomes.
PMCID: PMC1594694  PMID: 16954234
6.  Can anti-smoking television advertising affect smoking behaviour? Controlled trial of the Health Education Authority for England's anti-smoking TV campaign 
Tobacco Control  2000;9(3):273-282.
OBJECTIVES—To evaluate the effectiveness of the Health Education Authority for England's anti-smoking television advertising campaign in motivating smokers to give up and preventing relapse in those who had already given up.
DESIGN—A prospective, controlled trial was conducted in four TV regions in central and northern England. One region received no intervention (controls), two regions received TV anti-smoking advertising (TV media), and one region received TV anti-smoking advertising plus locally organised anti-tobacco campaigning (TV media + LTCN). The TV advertisements were screened in two phases over 18 months; during the first phase the intensity of the advertising was varied between TV regions. 5468 men and women (2997 smokers, 2471 ex-smokers) were selected by two stage random sampling and interviewed before the intervention, of whom 3610 were re-interviewed six months later, after the first phase of the campaign. Only those interviewed at six months were followed to the main end point at 18 months when 2381 subjects were re-interviewed.
MAIN OUTCOME MEASURES—Self reports of cigarette smoking at the 18 month follow up were compared between the three levels of intervention. Odds ratios for intervention effects were adjusted for pre-intervention predictors of outcome and pooled for smokers and ex-smokers using meta-analytic methods.
RESULTS—After 18 months, 9.8% of successfully re-interviewed smokers had stopped and 4.3% of ex-smokers had relapsed. The pooled adjusted odds ratio for not smoking in the TV media only condition compared to controls was 1.53 (95% confidence intervals (CI) 1.02 to 2.29, p = 0.04), and for TV media + LTCN versus controls, 1.67 (95% CI 1.0 to 2.8, p = 0.05). There was no evidence of an extra effect of the local tobacco control network when combined with TV media (odds ratio 1.15, 95% CI 0.74 to 1.78, p = 0.55). The was also no evidence of any intervention effects after the first phase of the TV media campaign, including no effect of varying the intensity of the advertising during this initial phase. Applying these results to a typical population where 28% smoke and 28% are ex-smokers, and where there would be an equal number of quitters and relapsers over an 18 month period without the campaign, suggests that the campaign would reduce smoking prevalence by about 1.2%.
CONCLUSIONS—The Health Education Authority for England's anti-smoking TV campaign was effective in reducing smoking prevalence through encouraging smokers to stop and helping prevent relapse in those who had already stopped. The lack of an effect after the first phase of the campaign indicates that if advertising at this intensity is to have an impact, a prolonged campaign is necessary. These results support the UK governments' recent decision to fund similar campaigns, and suggests that anti-smoking TV advertising should be undertaken routinely as an essential component of any population smoking reduction strategy. Reducing smoking prevalence would make a substantial contribution to achieving the UK government's target of preventing 300 000 cancer and heart disease deaths over the next 10 years.

Keywords: anti-smoking TV campaign; England; smoking cessation
PMCID: PMC1748378  PMID: 10982571
7.  Recombinant Hepatitis A Virus Antigen: Improved Production and Utility in Diagnostic Immunoassays 
Journal of Clinical Microbiology  1998;36(7):2014-2018.
Hepatitis A virus (HAV) immunoassays use cell culture-derived HAV antigen to detect HAV-specific antibodies. The current method of production of HAV antigen in tissue culture is time-consuming and expensive. We previously expressed the HAV open reading frame in recombinant vaccinia viruses (rV-ORF). The recombinant HAV polyprotein was accurately processed and was assembled into subviral particles. These particles were bound by HAV-neutralizing antibodies and were able to elicit antibodies which were detected by commercial immunoassays. The present investigation compared the production of HAV antigen by standard tissue culture methods to the production of HAV antigen with the recombinant vaccinia virus system. In addition, HAV and rV-ORF antigens were assessed for their utility in diagnostic immunoassays. Serum or plasma samples from HAV antibody-positive and antibody-negative individuals were evaluated by immunoassay that used either HAV or rV-ORF antigen. All samples (86 of 86) in which HAV antibody was detected by a commercial enzyme-linked immunosorbent assay (ELISA) also tested positive by the recombinant antigen-based immunoassay (VacRIA). Similarly, all samples (50 of 50) that were HAV antibody negative also tested negative by the VacRIA. The lower limit of detection of HAV antibody was similar among immunoassays with either HAV or rV-ORF antigen. Thus, in the population studied, the sensitivity and specificity of the VacRIA were equivalent to those of the commercial ELISA. Since production of recombinant antigen is faster and less expensive than production of traditional HAV antigen, the development of diagnostic HAV antibody tests with recombinant HAV antigen appears warranted.
PMCID: PMC104969  PMID: 9650953
8.  Glycerol particle cigarettes: a less harmful option for chronic smokers. 
Thorax  1993;48(4):385-387.
In 20 smokers who switched to a new type of virtually tar free cigarette for three days, average nicotine intake was reduced by 44%, carbon monoxide intake increased by 19%, while estimated tar intake was reduced by about 90%. Such cigarettes pose substantially less risk of cancer and chronic obstructive lung disease than conventional cigarettes, and their acceptability and safety could be improved by increasing nicotine yield, reducing carbon monoxide yield, and improving the flavour.
PMCID: PMC464438  PMID: 8511737
9.  Parasitism of Nematodes by the Fungus Hirsutella rhossiliensis as Affected by Certain Organic Amendments 
Journal of Nematology  1994;26(2):152-161.
Experiments were conducted to determine whether the addition of organic matter to soil increased numbers of bacterivorous nematodes and parasitic activity of the nematophagous fungus Hirsutella rhossiliensis. In a peach orchard on loamy sand, parasitism of the plant-parasitic nematode Criconemella xenoplax by H. rhossiliensis was slightly suppressed and numbers of C. xenoplax were not affected by addition of 73 metric tons of composted chicken manure/ha. In the laboratory, numbers of bacterivorous nematodes (especially Acrobeloides spp.) and fungivorous nematodes increased but parasitism of nematodes by H. rhossiliensis usually decreased with addition of wheat straw or composted cow manure to a loamy sand naturally infested with H. rhossiliensis. These results do not support the hypothesis that organic amendments will enhance parasitism of nematodes by H. rhossiliensis.
PMCID: PMC2619489  PMID: 19279878
bacterivorous nematode; biocontrol; biological control; Criconemella xenoplax; density-dependent parasitism; fungivorous nematode; Hirsutella rhossiliensis; nematode; nematophagous fungus; organic amendment
10.  Targeting heavy smokers in general practice: randomised controlled trial of transdermal nicotine patches. 
BMJ : British Medical Journal  1993;306(6888):1308-1312.
OBJECTIVES--(a) To evaluate the efficacy of transdermal nicotine patches as an aid to stopping smoking when used as an adjunct to brief advice and support in a general practice setting; (b) to see whether an increase in nicotine patch dosage enhances the rate of initial cessation. DESIGN--Randomised double blind placebo controlled parallel group study with one year of follow up. SETTING--30 general practices in 15 English counties. SUBJECTS--600 dependent heavy smokers (> or = 15 cigarettes daily) who were well motivated to give up. INTERVENTIONS--Brief general practitioner advice, booklet, and 16 hours per day patch treatment for 18 weeks with brief support and follow up at one, three, six, 12, 26, and 52 weeks. MAIN OUTCOME MEASURES--Self reported complete abstinence for up to one year with biochemical validation at all follow up points. RESULTS--Nicotine patches reduced the severity of craving and adverse mood changes in the first weeks of withdrawal and doubled the rate of initial cessation at week 3 (nicotine group 36% of patients (144/400), placebo group 16.5% of patients (33/200)) and of continuous abstinence throughout one year (nicotine group 9.3% (37), placebo group 5.0% (10)). A dose increase at week 1 among patients experiencing difficulty in quitting increased the proportion who achieved abstinence at week 3. There were no adverse systemic effects attributable to nicotine, but the incidence of moderate or severe local irritation or itching at the patch site was 16.4% (63 patients), compared with 3.8% (seven) with placebo. CONCLUSION--Transdermal nicotine patches used as an adjunct to brief advice and support in a general practice setting are an effective aid to long term cessation of smoking in highly dependent smokers.
PMCID: PMC1677738  PMID: 8518572
11.  Antigenic and immunogenic properties of recombinant hepatitis A virus 14S and 70S subviral particles. 
Journal of Virology  1993;67(2):1080-1085.
Hepatitis A virus (HAV) has an immunodominant neutralization antigenic site. By using a panel of monoclonal antibodies targeted against the HAV neutralization antigenic site, it was shown that three epitopes within this site are present on 14S subunits (pentamers of the structural unit). In contrast, two other epitopes within this site are formed upon assembly of 14S subunits into capsids. Thus, the epitopes recognized by these two monoclonal antibodies are formed either by a conformational change in the antigenic site or by the juxtaposition of epitope fragments present on different 14S subunits during assembly of 14S into 70S particles. Both 14S and 70S particles elicited HAV-neutralizing antibodies in mice; thus, these particles may be useful for HAV vaccine development.
PMCID: PMC237464  PMID: 7678298
12.  Establishment of Orchards with Black Polyethylene Film Mulching: Effect on Nematode and Fungal Pathogens, Water Conservation, and Tree Growth 
Journal of Nematology  1992;24(4S):681-687.
Placement of a 3-m-wide, black, polyethylene film mulch down rows of peach (Prunus persica 'Red Haven' on 'Lovell' rootstock) and almond (Prunus dulcis 'Nonpareil' on 'Lovell') trees in the San Joaquin Valley of California resulted in irrigation water conservation of 75%, higher soil temperature in the surface 30 cm, a tendency toward greater root mass, elimination of weeds, and a greater abundance of Meloidogyne incognita second-stage juveniles in soil but reduced root galling when compared to the nonmulched control. Population levels of Pratylenchus hexincisus, a nematode found within tree roots, were reduced by mulching, as were those of Tylenchulus semipenetrans, which survived on old grape roots remaining from a previously planted vineyard, and Paratrichodorus minor, which probably fed on roots of various weed species growing in the nonmulched soil. Populations of Pythium ultimum were not significantly changed, probably also due to the biological refuge of the old grape roots and moderate soil heating level. Trunk diameters of peach trees were increased by mulching, but those of almond trees were reduced by the treatment. Leaf petiole analysis indicated that concentrations of mineral nutrients were inconsistent, except for a significant increase in Ca in both tree species.
PMCID: PMC2629876  PMID: 19283045
almond; irrigation management; Meloidogyne incognita; mulching; nematode; peach; Paratrichodorus minor; Paratylenchus hamatus; Pratylenchus hexincisus; Prunus dulcis; Prunus persica; Pythium ultimum; soil heating; solarization; Tylenchulus semipenetrans
13.  The hepatitis A virus polyprotein expressed by a recombinant vaccinia virus undergoes proteolytic processing and assembly into viruslike particles. 
Journal of Virology  1991;65(9):5029-5036.
Hepatitis A virus (HAV) contains a single-stranded, plus-sense RNA genome with a single long open reading frame encoding a polyprotein of approximately 250 kDa. Viral structural proteins are generated by posttranslational proteolytic processing of this polyprotein. We constructed recombinant vaccinia viruses which expressed the HAV polyprotein (rV-ORF) and the P1 structural region (rV-P1). rV-ORF-infected cell lysates demonstrated that the polyprotein was cleaved into immunoreactive 29- and 33-kDa proteins which comigrated with HAV capsid proteins VP0 and VP1. The rV-P1 construct produced a 90-kDa protein which showed no evidence of posttranslational processing. Solid-phase radioimmunoassays with human polyclonal anti-HAV sera and with murine or human neutralizing monoclonal anti-HAV antibodies recognized the rV-ORF-infected cell lysates. Sucrose density gradients of rV-ORF-infected cell lysates contained peaks of HAV antigen with sedimentation coefficients of approximately 70S and 15S, similar to those of HAV empty capsids and pentamers. Immune electron microscopy also demonstrated the presence of viruslike particles in rV-ORF-infected cell lysates. Thus, the HAV polyprotein expressed by a recombinant vaccinia virus demonstrated posttranslational processing into mature capsid proteins which assembled into antigenic viruslike particles.
PMCID: PMC248966  PMID: 1651421
14.  Prospective study of factors predicting uptake of smoking in adolescents. 
Risk factors for the uptake of cigarette smoking were examined prospectively in 2159 non-smoking secondary schoolchildren aged 11-13 who participated in a survey in 1983 and were followed up 30 months later, by which time 35 per cent had taken up smoking. In a multivariate logistic model, the strongest predictors to emerge were prior experimentation with cigarettes and sex, with more girls (41%) than boys (30%) starting to smoke. Other predictors of taking up smoking were being uncertain about smoking in the future, reporting having been drunk, having a boy or girl friend, believing teachers and friends would not mind if they took up smoking, and giving lower estimates of prevalence of smoking among teachers. Parental smoking behaviour and attitudes, beliefs about the effects of smoking on health, opinions about smoking and perceived strictness of parents did not predict take up of smoking when other variables were controlled for. The odds of taking up smoking varied from 0.24 (risk = 0.19) for a child with the most favourable combination of risk factors to 3.49 (risk = 0.78) for a child with the worst prognosis. These results differ from those of many cross sectional studies and hence indicate the importance of a prospective approach to this type of research.
PMCID: PMC1052794  PMID: 2592895
15.  Use of a contraindications checklist by practice nurses performing immunizations at a well child clinic. 
At the inception of a general practice well child clinic, a checklist card was introduced into the clinic notes to summarize specific and relative contraindications to immunizations. This card was used by the practice nurses as they ran the immunization procedures during the clinic. A failure on the checklist led to a consultation with the clinic doctor who decided whether to proceed with the immunization. Of 155 immunizations given during the six-month period, only 23 (15%) failed the checklist and required the child to be assessed by the clinic doctor. Of these, nine (39%) were for simple upper respiratory tract infection. All the children were deemed fit to receive immunization. Only one child was found to have a specific contraindication to pertussis. The checklist cards allowed the smooth operation of the immunization procedures by practice nurses who were able to check comprehensively whether there were any contraindications and whether immunizations were being inappropriately refused.
PMCID: PMC1711751  PMID: 2552093
16.  District programme to reduce smoking: can sustained intervention by general practitioners affect prevalence? 
A total of 101 general practitioners in 27 practices in inner London took part in a quasi-experimental study designed to examine whether a brief intervention applied to all smokers seen by general practitioners and sustained on a continuous basis could in time have a cumulative effect and reduce the prevalence of smoking among their patients. Of 21 practices approached in our local district (Camberwell), seven were willing to undertake brief intervention with support from the smokers' clinic (SBI), four opted for intervention without support (BI), and six acted as usual care controls. A further 10 out of 12 practices approached in South Hammersmith provided an unselected group of usual care controls. A series of six cross-sectional surveys were conducted over a three-year period. Each survey consisted of all adult patients attending to see a doctor during a defined two-week period, sample sizes averaging just over 9000 per survey. The estimated decline in self-reported smoking prevalence over the 30-month period following the start of intervention was 5.5% (from 36.4% to 30.9%) in the SBI group compared with 2.1% for BI and 2.8% and 3.0% in the two usual care control groups, the decline in the SBI group being significantly greater than in the other groups which did not differ significantly between each other. These interim results provide encouraging evidence that brief intervention by general practitioners with support and back-up from a local smokers' clinic can, when sustained on a continuous basis, reach sufficient smokers to reduce smoking prevalence in their practice populations. However, firm conclusions must await longer periods of observation now that the other Camberwell practices have adopted the SBI procedures.
PMCID: PMC1052702  PMID: 3265427
17.  In vitro assay to demonstrate high-level erythromycin resistance of a clinical isolate of Treponema pallidum. 
We have previously demonstrated that cells of Treponema pallidum freshly extracted from infected rabbit testes can be intrinsically radiolabeled with [35 S]methionine to very high specific activities. In this study we used the inhibition of [35 S]methionine incorporation into trichloroacetic acid-precipitable protein in vitro as an assay to test the susceptibilities of three different pathogenic treponemal strains to various antibiotics. In general, the results correlated very well with the known efficacies of these antibiotics in treating human patients with syphilis. One of the strains tested, however, a clinical isolate of T. pallidum designated street strain 14, was found to exhibit high-level resistance to erythromycin and a closely related macrolide, roxithromycin (RU 965). Street strain 14 was originally isolated from a human patient with active secondary syphilis who failed to respond to erythromycin therapy. Thus, our results indicate that an erythromycin-resistant strain of T. pallidum can be responsible for erythromycin treatment failure. In addition, street strain 14 treponemes were found to be generally less susceptible by this assay to a variety of antibiotics than were treponemes of the T. pallidum Nichols strain. These findings suggest that the outer envelope of street strain 14 treponemes may be generally less permeable to antibiotics than is that of Nichols strain treponemes.
PMCID: PMC172128  PMID: 3284454
18.  District programme to reduce smoking: effect of clinic supported brief intervention by general practitioners. 
By encouraging and supporting general practitioners to undertake brief intervention on a routine basis smokers' clinics could reach many more smokers than are willing to attend for intensive treatment. In a study with 101 general practitioners from 27 practices 4445 cigarette smokers received brief intervention with the support of a smokers' clinic, brief intervention without such support, or the general practitioners' usual care. At one year follow up the numbers of smokers who reported that they were no longer smoking cigarettes were 51 (13%), 63 (9%), and 263 (8%), respectively (p less than 0.005). After an adjustment was made for those cases not validated by urine cotinine concentrations the respective success rates were 8%, 5%, and 5%. Use of nicotine chewing gum was associated with higher self reported success rates. General practitioners providing supported brief intervention encouraged not only more smokers to use the gum but also more effective use; gum users in this group reported a success rate of 27% at one year. Compliance by the general practitioners in recording smoking state averaged 45%, and significantly higher success rates were reported by patients whose smoking state had been recorded. Brief intervention by general practitioners with the support of a smokers' clinic thus significantly enhanced success rates based on self reports. Better results might be obtained if general practitioners' compliance with the procedure could be improved and if they encouraged more of their patients to try nicotine gum. Collaboration of this kind between a smokers' clinic and local general practitioners could deliver effective help to many more smokers than are likely to be affected if the two continue to work separately.
PMCID: PMC1248311  PMID: 3120963
19.  Neutralization escape mutants define a dominant immunogenic neutralization site on hepatitis A virus. 
Journal of Virology  1987;61(2):491-498.
Hepatitis A virus is an hepatotrophic human picornavirus which demonstrates little antigenic variability. To topologically map immunogenic sites on hepatitis A virus which elicit neutralizing antibodies, eight neutralizing monoclonal antibodies were evaluated in competition immunoassays employing radiolabeled monoclonal antibodies and HM-175 virus. Whereas two antibodies (K3-4C8 and K3-2F2) bound to intimately overlapping epitopes, the epitope bound by a third antibody (B5-B3) was distinctly different as evidenced by a lack of competition between antibodies for binding to the virus. The other five antibodies variably blocked the binding of both K3-4C8-K3-2F2 and B5-B3, suggesting that these epitopes are closely spaced and perhaps part of a single neutralization immunogenic site. Several combinations of monoclonal antibodies blocked the binding of polyclonal human convalescent antibody by greater than 96%, indicating that the neutralization epitopes bound by these antibodies are immunodominant in humans. Spontaneously arising HM-175 mutants were selected for resistance to monoclonal antibody-mediated neutralization. Fourteen clonally isolated mutants demonstrated substantial resistance to multiple monoclonal antibodies, including K3-4C8-K3-2F2 and B5-B3. In addition, 13 mutants demonstrated a 10-fold or greater reduction in neutraliztion mediated by polyclonal human antibody. Neutralization resistance was associated with reduced antibody binding. These results suggest that hepatitis A virus may differ from poliovirus in possessing a single, dominant neutralization immunogenic site and therefore may be a better candidate for synthetic peptide or antiidiotype vaccine development.
PMCID: PMC253973  PMID: 2433464
21.  Effect of nicotine chewing gum as an adjunct to general practitioner's advice against smoking. 
This study was designed to see whether the offer and prescription of nicotine chewing gum would enhance the efficacy of general practitioners' advice to stop smoking. A sample of 1938 cigarette smokers who attended the surgeries of 34 general practitioners in six group practices were assigned by week of attendance (in a balanced design) to one of three groups: (a) non-intervention controls, (b) advice plus booklet, and (c) advice plus booklet plus the offer of nicotine gum. Follow up was done after four months and one year. The results show a clear advantage for those offered the nicotine gum (p less than 0.001). After correction for those who refused or failed chemical validation and those who switched from cigarettes to a pipe or cigars, the proportions who were abstinent at four months and still abstinent at one year were 3.9%, 4.1%, and 8.8% in the three groups, respectively. These percentages are based on all cigarette smokers who attended the surgeries including those who did not wish to stop and those in the gum group who did not try the gum (47%). The effect of the offer and prescription of gum was to motivate more smokers to try to stop, to increase the success rate among those who tried, and to reduce the relapse rate of those who stopped. The self selected subgroup of 8% who used more than one box of 105 pieces of gum achieved a success rate of 24%. It would be feasible and effective for general practitioners to include the offer of nicotine gum and brief instructions on its use as part of a minimal intervention routine with all cigarette smokers. A general practitioner who adopts such a routine with similar success could expect to achieve about 35-40 long term ex-smokers a year and so save the lives of about 10 of them. If replicated by all general practitioners throughout the country the yield of ex-smokers would be about one million a year.
PMCID: PMC1549849  PMID: 6416593
22.  Postoperative pain. 
British Medical Journal  1978;2(6150):1499.
PMCID: PMC1608710  PMID: 719499
24.  Therapeutic abortion in a Canadian city. 
Canadian Medical Association Journal  1970;103(10):1085-passim.
PMCID: PMC1930729  PMID: 5494832

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