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D N Lawrence

Publications and source records attributed to D N Lawrence.

At least 19 recordsLinked to original sources
PubMed2003

Long-term safety analysis of preventive HIV-1 vaccines evaluated in AIDS vaccine evaluation group NIAID-sponsored Phase I and II clinical trials.

This report evaluates long-term safety data from 3189 human immunodeficiency virus type 1 (HIV-1) uninfected, healthy volunteers who were enrolled into 51 National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Phase I and II multicentred, randomized, double-blind trials of recombinant HIV-1 subunit vaccines (23 studies), synthetic peptide vaccines (7 studies), live vaccinia-vector recombinant envelope vaccines (7 studies), canarypox vector recombinant vaccines (13 studies), a DNA vaccine (1 study), and a Salmonella-vector vaccine (1 study). During the 12,340 person-years of follow-up, participants were monitored for adverse events including immune dysfunction/autoimmunity, anaphylaxis, cancer, death, and vaccine allergy. The analysis provides evidence that a preparation of a C4-V3 polypeptide vaccine emulsified in incomplete Freund's caused serious toxicity, but otherwise no safety problems considered serious were identified for any of the vaccines and adjuvants studied. These data serve to solidify the growing safety base of current vaccine technologies utilized in candidate vaccines for HIV-1 infection.

AIDS Vaccines↗
PubMed1995

Public health implications of emerging vaccine technologies.

The field of public health and medicine stands to benefit immensely from the emerging vaccine technologies and improved application of existing technologies. Technological advances may promote: (1) greater flexibility and simplicity in the design and operation of immunization campaigns or ongoing prevention programs, including reduction in number of vaccine doses, cold chain elimination, slow-release/prolonged antigenic stimulation, reduced cost and hazard and increased ease of administration through noninvasive, oral delivery systems, greater population levels of immunization and health; (2) the development of documents by FDA, WHO, and other regulatory authorities and groups, to assist the manufacturer in the appropriate manufacturing, preclinical, and clinical development of these new vaccines; (3) a greater array of vaccines to protect the civilian and military populations; (4) increased vaccine potency; (5) vaccines eliciting mucosal immunity, cytotoxic T cells, and/or neutralizing antibody. At the end of the 20th century there remain many unconquered pathogens and noninfectious indications for which medical science suggests that vaccines could be effective. New technologies may provide the best hope to address this wide array of public health needs.

Humans↗
PubMed1992

Native American mitochondrial DNA analysis indicates that the Amerind and the Nadene populations were founded by two independent migrations.

Mitochondrial DNAs (mtDNAs) from 167 American Indians including 87 Amerind-speakers (Amerinds) and 80 Nadene-speakers (Nadene) were surveyed for sequence variation by detailed restriction analysis. All Native American mtDNAs clustered into one of four distinct lineages, defined by the restriction site variants: HincII site loss at np 13,259, AluI site loss at np 5,176, 9-base pair (9-bp) COII-tRNA(Lys) intergenic deletion and HaeIII site gain at np 663. The HincII np 13,259 and AluI np 5,176 lineages were observed exclusively in Amerinds and were shared by all such tribal groups analyzed, thus demonstrating that North, Central and South American Amerinds originated from a common ancestral genetic stock. The 9-bp deletion and HaeIII np 663 lineages were found in both the Amerinds and Nadene but the Nadene HaeIII np 663 lineage had a unique sublineage defined by an RsaI site loss at np 16,329. The amount of sequence variation accumulated in the Amerind HincII np 13,259 and AluI np 5,176 lineages and that in the Amerind portion of the HaeIII np 663 lineage all gave divergence times in the order of 20,000 years before present. The divergence time for the Nadene portion of the HaeIII np 663 lineage was about 6,000-10,000 years. Hence, the ancestral Nadene migrated from Asia independently and considerably more recently than the progenitors of the Amerinds. The divergence times of both the Amerind and Nadene branches of the COII-tRNA(Lys) deletion lineage were intermediate between the Amerind and Nadene specific lineages, raising the possibility of a third source of mtDNA in American Indians.

Asian People↗
PubMed1991

Reassessment of the association between Guillain-Barré syndrome and receipt of swine influenza vaccine in 1976-1977: results of a two-state study. Expert Neurology Group.

Although the original Centers for Disease Control study of the relation between A/New Jersey/8/76 (swine flu) vaccine and Guillain-Barré syndrome (polyradiculoneuritis) demonstrated a statistical association and suggested a causal relation between the two events, controversy has persisted. To reassess this association, the authors obtained medical records of all previously reported adult patients with Guillain-Barré syndrome in Michigan and Minnesota from October 1, 1976 through January 31, 1977. To identify previously unreported hospitalized cases with onset of symptoms during this period, the authors surveyed medical care facilities. A group of expert neurologists formulated diagnostic criteria for Guillain-Barré syndrome and then reviewed the clinical records in a blinded fashion. Of the 98 adult patients from the original Centers for Disease Control study eligible for consideration, three were found to have been misclassified by date of onset and were excluded. Of the remaining 95, the 28 (29%) who did not meet the diagnostic criteria were equally distributed between the vaccinated group (18 of 60, 30%) and the unvaccinated group (10 of 35, 29%). In addition to the 67 remaining cases who met the diagnostic criteria, six previously unreported cases (three of whom had been vaccinated) were found and included in this analysis. The relative risk of developing Guillain-Barré syndrome in the vaccinated population of these two states during the 6 weeks following vaccination was 7.10, comparable to the relative risk of 7.60 found in the original study. These findings suggest that there was an increased risk of developing Guillain-Barré syndrome during the 6 weeks following vaccination in adults. The excess cases of Guillain-Barré syndrome during the first 6 weeks attributed to the vaccine was 8.6 per million vaccinees in Michigan and 9.7 per million vaccinees in Minnesota. No increase in relative risk for Guillain-Barré syndrome was noted beyond 6 weeks after vaccination.

Causality↗
PubMed1990

HIV transmission to patients with hemophilia by heat-treated, donor-screened factor concentrate.

Six hemophilia patients previously seronegative for human immunodeficiency virus (HIV) seroconverted between September 1986 and September 1987. None had risk factors for HIV infection other than hemophilia. We compared the factor concentrates received by these patients with the concentrates received by 10 seronegative hemophilia patients. A statistically significant association was observed between seropositivity and the receipt of two lots of Factor VIII produced from the same plasma pool (odds ratio 77, p = 0.0014); five of the six case subjects but none of the control subjects had received concentrate from one of the two lots. Available evidence suggests that the sixth case subject had also received concentrate from an implicated lot. Symptoms including rash and fever were reported in five cases within 6 weeks after the implicated concentrate had been given. The implicated lots were produced from plasma from paid donors that had been screened and then heated at 60 degrees C for 30 hours in the lyophilized state. Subsequent to our investigation all concentrate produced by this process was removed from distribution.

Adolescent↗
PubMed1990

Amerindian mitochondrial DNAs have rare Asian mutations at high frequencies, suggesting they derived from four primary maternal lineages.

The mitochondrial DNA (mtDNA) sequence variation of the South American Ticuna, the Central American Maya, and the North American Pima was analyzed by restriction-endonuclease digestion and oligonucleotide hybridization. The analysis revealed that Amerindian populations have high frequencies of mtDNAs containing the rare Asian RFLP HincII morph 6, a rare HaeIII site gain, and a unique AluI site gain. In addition, the Asian-specific deletion between the cytochrome c oxidase subunit II (COII) and tRNA(Lys) genes was also prevalent in both the Pima and the Maya. These data suggest that Amerindian mtDNAs derived from at least four primary maternal lineages, that new tribal-specific variants accumulated as these mtDNAs became distributed throughout the Americas, and that some genetic variation may have been lost when the progenitors of the Ticuna separated from the North and Central American populations.

Asia↗
PubMed1990

A review of clinical studies evaluating the efficacy of HIV inactivation methods.

Seroconversion surveillance is informative and must be continued. The level of safety is now so high that individual candidate cases of seroconversion need exquisite investigation to exclude the possibility of another source of the HIV infection. Consequently, we must be mindful that the inappropriate assignment of an HIV seroconversion incident to a blood product not only misrepresents the risk associated with currently available blood products, but may unfairly and devastatingly damage the reputation of a necessary and precious biological product. Inappropriate anxiety about a product, with resultant abandonment of its therapeutic benefit, may drastically reduce available factor concentrates, encourage price escalations associated with shortages, and lead unsettled patients to reduce their levels of prescribed therapy--with life threatening consequences. By monitoring the HIV-antibody testing records for all collection sites of a company's source plasma procurement network, the number and percent of donors found to be confirmably HIB-antibody positive might provide a clue to possible changes in the level of the undetected virus burden introduced into the source plasma supply. However, the combined efforts to develop higher purity products, combined with stringent inactivation methods has resulted in a product mix in use in the U.S. and elsewhere that seems to carry a risk of HIV seroconversion of less than 1 per 1000 patient-years of therapy.

Biological Products↗
PubMed1989

Sex practice correlates of human immunodeficiency virus transmission and acquired immunodeficiency syndrome incidence in heterosexual partners and offspring of U.S. hemophilic men.

We assessed the risk of human immunodeficiency virus (HIV) transmission from heterosexual seropositive hemophilic men to their female sex partners through an HIV serosurvey and questionnaire study conducted during 1984-1987. Five percent of 21 female partners of asymptomatic men and 11% of 35 partners of HIV-symptomatic (acquired immunodeficiency syndrome [AIDS], AIDS-related complex [ARC], peripheral generalized lymphadenopathy [PGL]) hemophilic men had been infected when first tested. One of 19 seronegative women tested about 1 year later reportedly seroconverted. Only 18% of a sample of the serosurvey women responding to sex practices questions said their partners used condoms "nearly always." Over 60% engaged in oral/genital sex in addition to vaginal intercourse. Only 12% of still-seronegative women followed the preventive strategy of consistent avoidance of oral/genital sex, together with consistent condom use by the male partner. Further evidence for heterosexual transmission comes from the CDC national AIDS surveillance reports showing 25 women who acquired HIV infection through heterosexual contact with U.S. hemophilic men (September 6, 1988). Seven (28%) were diagnosed and reported in the first 6 months of 1988. Their ages range from 20 years to more than 70 years. The dates of infection for the women are unknown but must have been at least 5 years before AIDS diagnosis for at least one. Only approximately 30% of their male partners had already manifested any HIV-associated illness. Through May 18, 1988, six cases of AIDS have occurred in children whose infection was acquired through exposure of the mother to a hemophilic partner. Four were diagnosed in latter 1987. The median age at diagnosis was 4.5 months. Four had died. None of their mothers is as yet diagnosed.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Prevalence of human immunodeficiency virus type 1 DNA in hemophilic men and their sex partners. Hemophilia-AIDS Collaborative Study Group.

Polymerase chain reaction (PCR) was used to detect human immunodeficiency virus (HIV)-1 DNA in peripheral blood mononuclear cells to assess in hemophilic men whether any were HIV-seropositive but uninfected or seronegative but infected and in seronegative sex partners of seropositive hemophilic men whether any were infected. Of 40 seropositive men, 38 (95%) were PCR-positive; one was PCR-indeterminate and one PCR-negative. None of 41 seronegative men who used only donor-screened, virus-inactivated coagulation factor products were PCR-positive. However, two of six who received noninactivated products were PCR-positive; one had low T-helper cell counts and died of unrelated causes and the other had seroconverted 11 mo later. PCR with a second primer pair also detected HIV-1 DNA in these two men. None of 25 seronegative female sex partners of seropositive men, including six men with AIDS and seven with AIDS-related symptoms, were PCR-positive. These data suggest that most seropositive hemophilic men are HIV-infected; whether some are infected with defective virus remains to be resolved as does the infection status of seropositive PCR-negative men. Identification of two seronegative PCR-positive men supports the possibility that HIV-1 DNA can be detected before seroconversion.

DNA, Viral↗
PubMed1989

HIV and hemophilic children's growth.

The acquired immune deficiency syndrome (AIDS) often has profound effects on growth; however, the effects of human immunodeficiency virus (HIV) on asymptomatic children's growth are unknown. Before heat inactivation/HIV donor screening of factor concentrates, many hemophilic children became infected with HIV. We evaluated four hemophilic groups without AIDS, using age-standardized growth parameters: group 1, 41 HIV-seropositive children (median age of 13 years); group 2, 11 HIV-seronegative children (median age of 4 years); group 3, 20 children frequently receiving concentrates, evaluated before 1979 (median age of 9 years); and group 4, 11 children rarely receiving concentrates, evaluated before 1979 (median age of 6 years). Median height for age (HA), weight for age (WA), and weight for height (WH) of groups 1 and 2 exceeded the 50th percentile of referent norms. HA, WA, WH, and weight/height did not vary significantly by group, nor did these decline over periods of 11 to 70 months. However, for those less than 11 years of age in group 1, HA declined by 25 percentile points over at least a 3 year period. Also, group 1's T helper-to-suppressor cell ratios at 12 +/- 3 months following the latest growth evaluation were positively associated with both HA and WA at the last evaluation. Eight children were evaluated before 1979 and again after they seroconverted to HIV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Acquired immune deficiency syndrome associated with hemophilia in the United States.

Persons with hemophilia and other coagulation disorders were at risk for infection with HIV as a result of receiving blood products, particularly concentrated clotting factors. Because these products are now donor-screened and heat-treated to inactivate HIV, the risk of further infection in this population has been minimized. However, before the introduction of these interventions, many persons with hemophilia had been infected. As of Jan 4, 1988, 463 cases of hemophilia-associated AIDS had been reported to the Centers for Disease Control. Most patients had severe hemophilia and received commercially produced concentrated clotting factors. These patients may constitute as many as 25% of those hemophilic men known to be infected with HIV. Through heterosexual and perinatal transmission, the partners and offspring of persons with hemophilia can become infected with HIV. The seroprevalence rate for female sex partners of men with hemophilia may be as high as 21%, and 16 AIDS cases have already been reported. Counseling and public health interventions are needed to prevent the further spread of HIV infection in sex partners and offspring of these patients and to prevent the associated morbidity and fatalities. Because HIV infection can be transmitted by exposure to infected blood or blood components, health-care workers whose activities involve contact with infected blood or body fluids are also at risk for HIV infection. Prospective studies suggest this risk is very low; nevertheless, health-care workers need to adhere rigorously to infection-control precautions to minimize the risk of exposure to blood and body fluids. These precautions include wearing gloves, masks, protective eyewear, and gowns depending on the type of exposure anticipated.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1988

A model-based approach to characterize the incubation period of paediatric transfusion-associated acquired immunodeficiency syndrome.

Traditional statistics, such as the average, currently provide a misleading statistical description of the incubation periods of paediatric transfusion-associated acquired immunodeficiency syndrome (TA-AIDS). Two types of length-biased sampling, left censoring and right censoring, occur in the 37 cases diagnosed before 1986 and reported to the Centers for Disease Control by 15 September 1986. To correct for these problems, we propose a truncated Weibull distribution with use of a maximum likelihood technique. This approach suggests that the mean incubation period of paediatric TA-AIDS cases is 2.4 years with a 90 per cent confidence interval ranging from 1.5 years to 7.2 years. The mode is 1.25 years. These estimates are much shorter than those recently published for adults, therefore the success of TA-AIDS prevention strategies may be seen sooner in the paediatric age group.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Community outbreak of thyrotoxicosis: epidemiology, immunogenetic characteristics, and long-term outcome.

Between January and March 1984, the first community outbreak of transient thyrotoxicosis in the United States was documented in a seven-county area of southeastern Nebraska; 36 of the total 49 patients resided in York County (2.4 cases per 1,000 population). The median age of patients was 36 years, range six to 82 years; 51 percent were women. By definition, all patients were symptomatic, visited a physician, and had a newly identified elevated serum concentration of thyroxine or triiodothyronine of unknown cause. None had a goiter or a painful thyroid gland. Low 131I uptake measurements were found in all nine patients studied. Six patients were hospitalized; none died. Investigation of all 12 household contacts of eight selected patients revealed five additional persons with thyrotoxicosis and four with asymptomatic hyperthyroxinemia. A case-control study revealed that illness was associated with a significantly higher frequency of a reported recent respiratory viral-like condition. In another case-control study, the HLA-DR3 antigen was present in more case subjects (39 percent) than control subjects (14 percent). In addition, a significantly higher proportion of patients than control subjects purchased beef from one of the three supermarkets in York Country. Concomitant with the outbreak, the supermarket implicated in the outbreak purchased an unusually large quantity of beef (7,000 pounds) from a nonregular supplier in Nebraska, which had reportedly instituted the practice of trimming gullets (a procedure that removes the muscles from bovine larynx for beef) about three months earlier. Thus, it is concluded that the Nebraska outbreak, like one in Minnesota that occurred 18 months later, probably resulted from patients having eaten ground beef that was contaminated with bovine thyroid gland. This form of thyrotoxicosis, perhaps misdiagnosed as painless thyroiditis in the past, probably represents a previously under-recognized public health problem.

Adult↗
PubMed1986

Effects of exposure to factor concentrates containing donations from identified AIDS patients. A matched cohort study.

We compared recipients of eight lots of factors VIII and IX voluntarily withdrawn from distribution because one donor was known to have subsequently developed the acquired immunodeficiency syndrome with a nonexposed cohort matched by age, sex, and factor use. The factor VIII recipient cohorts did not differ in prevalence of antibody to human immunodeficiency virus (HIV) (exposed, 75%; nonexposed, 86%), T-cell subset numbers (median: exposed, 619 T-helper cells per cubic millimeter; nonexposed, 659 T-helper cells per cubic millimeter), T-helper to T-suppressor ratios, or immunoglobulin levels. Exposed individuals had higher levels of immune complexes by C1q binding and staphylococcal binding assays and lower responses to phytohemagglutinin and concanavalin A. However, only the staphylococcal binding assay values were outside the normal range for our laboratory. Factor IX recipient cohorts did not differ in HIV antibody prevalence (exposed, 30%; nonexposed, 40%) or any immune tests. Although exposed and nonexposed individuals did not differ from each other in a clinically meaningful fashion at initial testing, both the exposed and nonexposed cohorts had high rates of HIV seroprevalence. Market withdrawals were clearly insufficient means of limiting the spread of HIV in hemophilic patients; however, the currently available methods of donor screening and viral inactivation of blood products will prevent continued exposure within this population.

Acquired Immunodeficiency Syndrome↗
PubMed1986

HTLV-III/LAV antibody and immune status of household contacts and sexual partners of persons with hemophilia.

We evaluated the human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) antibody and immune status of 88 persons living with and/or sexual partners of 43 hemophiliacs, 12 of whom had AIDS, five of whom had AIDS-related complex (ARC), 17 of whom were clinically well but HTLV-III/LAV antibody positive, and nine of whom were well and HTLV-III/LAV antibody negative. No nonhemophilic household contacts (0/50) of healthy hemophiliacs were HTLV-III/LAV antibody positive; two of 33 nonhemophilic AIDS/ARC contacts were positive. One was a spouse and one a sexual partner of a hemophiliac. One of these antibody-positive contacts herself had AIDS, and one had ARC. Antibody-negative, nonhemophilic contacts of AIDS/ARC and of antibody-positive hemophiliacs had significantly lower numbers of lymphocytes, T helper lymphocytes, and T suppressor lymphocytes than did contacts of antibody-negative hemophiliacs. We conclude that risk of HTLV-III/LAV transmission may exist for spouses and/or sexual contacts of hemophiliacs with AIDS/ARC, but we cannot now determine the risk for contacts of asymptomatic hemophiliacs.

Acquired Immunodeficiency Syndrome↗
PubMed1986

A model-based approach for estimating the mean incubation period of transfusion-associated acquired immunodeficiency syndrome.

The incubation period, representing the interval between the date of exposure and the date of diagnosis, can be firmly ascertained in transfusion-associated cases of acquired immunodeficiency syndrome (AIDS). However, because the observation period of all transfusion-infected persons may be short compared with the average incubation period for AIDS, many cases with long incubation periods have not yet been diagnosed. Thus, the simple average of 2.6 years tends to underestimate the true mean. To correct for this underestimation bias, we assumed that the underlying distribution of the incubation periods is a member of a broad class of probability densities. Then, by maximum likelihood techniques, the mean incubation period for transfusion-associated AIDS was estimated to be 4.5 years, with the 90% confidence interval ranging from 2.6 to 14.2 years. The long incubation period has important consequences for infected individuals and implications for public health intervention and prevention policy.

Acquired Immunodeficiency Syndrome↗