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Biomedical subjects

D Fuller

Publications and source records attributed to D Fuller.

At least 19 recordsLinked to original sources

Ability of new APTIMA CT and APTIMA GC assays to detect Chlamydia trachomatis and Neisseria gonorrhoeae in male urine and urethral swabs.

A clinical evaluation was conducted in six North American centers to determine the ability of APTIMA CT (ACT) and APTIMA GC (AGC) nucleic acid amplification assays to detect Chlamydia trachomatis and Neisseria gonorrhoeae infections in 1,322 men by testing their urethral swabs and first-catch urine (FCU). The results obtained with ACT and AGC assays were compared to an infected patient status determined by testing the specimens with the APTIMA Combo 2 and the BD ProbeTec energy transfer multiplex assays. Symptoms did not influence the values. Positive and negative agreements of the ACT and AGC assays for individual specimens were high, with each comparator assay ranging between 94.3 and 100% for positives and 93.9 and 99.4% for negatives. The ACT and AGC assays performed on noninvasive specimens such as FCU effectively identified C. trachomatis or N. gonorrhoeae infections in symptomatic and asymptomatic men and should be suitable for screening male populations.

Adolescent↗

Confirming positive results of nucleic acid amplification tests (NAATs) for Chlamydia trachomatis: all NAATs are not created equal.

The Centers for Disease Control and Prevention recommended confirming positive screening tests for Chlamydia trachomatis when positive predictive values are <90%. It is accepted that less sensitive tests (i.e., culture and immunoassays) should not be used to confirm the results of more sensitive nucleic acid amplification tests (NAATs). We show that the same principle applies when NAATs are used for confirmation.

Centers for Disease Control and Prevention, U.S.↗

I.V. busulfan in pediatrics: a novel dosing to improve safety/efficacy for hematopoietic progenitor cell transplantation recipients.

A retrospective population pharmacokinetic (PPK) analysis was performed in 24 pediatric patients (PEDS) (0.45-16.7 years old) receiving i.v. busulfan/cyclophosphamide (i.v. Bu/Cy 4) regimen prior to allogeneic hematopoietic stem cell transplantation. I.V. Bu doses were given as a 2-hour infusion every 6 h over 4 days. Initial dosing of i.v. Bu was 1 mg/kg for children < or =4 years old and 0.8 mg/kg for patients >4 years old. Bu plasma concentrations at doses 1, 9 and 13 were analyzed through a multivariate NONMEM analysis. A close log-linear relationship between body weight (BW) and i.v. Bu clearance was demonstrated with no further age-dependency or gender effect. The interpatient coefficient of variation (CV) in Bu clearance significantly decreased from 56% (covariate-free model) to 19% (BW covariate model) and reproducible i.v. Bu exposure between doses was illustrated (intraindividual CV=9%). Based on the PPK model, a novel Bu dosing regimen (ie: doses in mg/kg adjusted to discrete weight categories) for a better AUC targeting was developed by simulation on 1000 patients. Age-based dosing was demonstrated not to be clinically relevant with i.v. Bu. Use of the new BW-based dosing appears to be more appropriate for the PEDS.

Adolescent↗

Multicenter study assessing effects of heat and moisture exchanger use on respiratory symptoms and voice quality in laryngectomized individuals.

OBJECTIVE: A multicenter study based in the United States assessed the heat-moisture exchanger effect on respiratory symptoms and "voice quality" of laryngectomees. PATIENTS AND MEASURES: The study group consisted of 81 consecutive laryngectomees (62 men and 19 women; mean age, 66 years; age range, 45 to 89 years), with a median follow-up of 3.5 years (range, 0.5 to 24 years). A structured questionnaire was used to assess 3-month results, and tally sheets recorded the frequency of cough-expectoration during first and last trial weeks. RESULTS: Compliance was 73% (n = 59); decrease in coughing, 68%; sputum production, 73%; forced expectoration, 60%; and need for stoma cleaning, 52% of these 59 patients. Regarding daily cough-expectoration frequency, a statistically significant decrease (P < 0.0001) was found between the first and last trial weeks. Regarding influence on voice quality, 46% of regular users reported improvement in intelligibility, 30% in loudness, 37% in fluency, and 40% in telephone intelligibility. Fourteen patients (19%) reported skin irritation, with discontinuation of 7 patients. CONCLUSION: The observed decrease in pulmonary symptoms and improvement in voice quality confirm earlier reports from the Netherlands, United Kingdom, and Spain indicating improvement in postlaryngectomy quality of life.

Aged↗

Long-term results of blood and marrow transplantation for Hodgkin's lymphoma.

PURPOSE: To evaluate the long-term outcome after allogeneic (allo) and autologous (auto) blood or marrow transplantation (BMT) in patients with relapsed or refractory Hodgkin's lymphoma (HL). PATIENTS AND METHODS: We analyzed the outcome of 157 consecutive patients with relapsed or refractory HL, who underwent BMT between March 1985 and April 1998. Patients <or= age 55 with HLA-matched siblings were prioritized toward allo BMT. The median age was 28 years (range, 13 to 52 years) for the 53 allo patients and 30.5 years (range, 11 to 62 years) for the 104 auto patients. RESULTS: The median follow-up after BMT for surviving patients was 5.1 years (range, 1 to 13.8 years). For the entire group, the probabilities of event-free survival (EFS) and relapse at 10 years were 26% (95% confidence interval [CI], 18% to 33%) and 58% (95% CI, 48% to 69%), respectively. According to multivariate analysis, disease status before BMT (sensitive relapse if responding to conventional-dose therapy or resistant disease if not) (hazard ratio [HR] = 0.39, P < .0001) and date of BMT (HR = 0.93, P = .004) were independent predictors of EFS, whereas only disease status (HR = 0.35, P < .0001) influenced relapse. There was a trend for probability of relapse in sensitive patients to be less after allo BMT at 34% (range, 8% to 59%) versus 51% (range, 36% to 67%) for the auto patients (HR = 0.51, P = .17). There was a continuing risk of relapse or secondary acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) for 12 years after auto BMT, whereas there were no cases of secondary AML/MDS or relapses beyond 3 years after allo BMT. CONCLUSION: There seems to be a clinical graft-versus-HL effect associated with allo BMT. Allo BMT for HL also seems to have a lower risk of secondary AML/MDS than auto BMT. Thus, allo BMT warrants continued study in HL.

Adolescent↗

Expression patterns of cell-type-specific genes in Dictyostelium.

Cell-type specific genes were recognized by interrogating microarrays carrying Dictyostelium gene fragments with probes prepared from fractions enriched in prestalk and prespore cells. Cell-type specific accumulation of mRNA from 17 newly identified genes was confirmed by Northern analyses. DNA microarrays carrying 690 targets were used to determine expression profiles during development. The profiles were fit to a biologically based kinetic equation to extract the times of transcription onset and cessation. Although the majority of the genes that were cell-type enriched at the slug stage were first expressed as the prespore and prestalk cells sorted out in aggregates, some were found to be expressed earlier before the cells had even aggregated. These early genes may have been initially expressed in all cells and then preferentially turned over in one or the other cell type. Alternatively, cell type divergence may start soon after the initiation of development.

Animals↗

The cellulose synthase gene of Dictyostelium.

Cellulose is a major component of the extracellular matrices formed during development of the social amoeba, Dictyostelium discoideum. We isolated insertional mutants that failed to accumulate cellulose and had no cellulose synthase activity at any stage of development. Development proceeded normally in the null mutants up to the beginning of stalk formation, at which point the culminating structures collapsed onto themselves, then proceeded to attempt culmination again. No spores or stalk cells were ever made in the mutants, with all cells eventually lysing. The predicted product of the disrupted gene (dcsA) showed significant similarity to the catalytic subunit of cellulose synthases found in bacteria. Enzyme activity and normal development were recovered in strains transformed with a construct expressing the intact dcsA gene. Growing amoebae carrying the construct accumulated the protein product of dcsA, but did not make cellulose until they had developed for at least 10 hr. These studies show directly that the product of dcsA is necessary, but not sufficient, for synthesis of cellulose.

Amino Acid Sequence↗

Evaluation of protocols allowing emergency medical technicians to determine need for treatment and transport.

OBJECTIVE: To determine whether emergency medical technicians (EMTs) can safely apply protocols to assign transport options and to assess agreement between groups of providers on application of the protocols. METHODS: Developed protocols categorized patients as: 1) needs ambulance; 2) go to the emergency department (ED) by alternative means; 3) contact primary care provider (PCP); or 4) treat and release. After education on the application of the protocols, first responders and ambulance EMTs categorized patients at the scene prior to transport but did not change current practice. Ambulance reports were reviewed using a predetermined list of critical events that signified the need for an ambulance. RESULTS: The EMTs categorized 1,300 study patients as follows: 1,023 (79%) needed ambulance transport, 200 (15%) could go to the ED by alternative means, 63 (5%) could contact a PCP, 14 (1%) could be treated and released. Categorizations by a first responder and the transporting EMT were compared for 209 patients. Collapsing categories to "need ambulance/do not need ambulance" showed fair concordance (kappa = 0.51). Initially, 30 of 277 (11%) patients determined not to need an ambulance appeared to experience a critical event. After review, 23 patients had events that may not warrant advanced life support transport. Seven (3%) had critical events in the ambulance warranting ambulance transport. Most were miscategorized by the EMT. Overall sensitivity and specificity for identifying patients needing ambulance transport were 94.5% and 32.8%, respectively. CONCLUSIONS: From 3% to 11% of patients determined on scene not to need an ambulance had a critical event. Emergency medical services systems need to determine an acceptable rate of undertriage. Further study is needed to determine whether better adherence to the protocols might increase safety.

Adult↗

HIV-1 vaccine-induced immune responses which correlate with protection from SHIV infection: compiled preclinical efficacy data from trials with ten different HIV-1 vaccine candidates.

The specific immune mechanisms necessary and/or sufficient to elicit HIV-vaccine protection remain undefined. Utilising the SHIV rhesus macaque model the immunogenicity as well as the efficacy of ten different HIV-1 vaccine candidates was evaluated. Comparison of the immune responses induced, with the ability of the vaccine to protect from SHIV infection provided a means to determine which type of immune responses were necessary for protection. Vaccine candidates included VLPs, DNA, subunit protein with novel adjuvant formulations, ISCOMs and pox-virus vectors. Protection from SHIV infection was achieved in approximately half of the animals which received a primary intravenous cell-free challenge. The presence of CTL in the absence of other effector responses did not correlate with protection from this route and type of challenge. Virus neutralising antibodies (Nab) appeared to be necessary but alone were insufficient for protection. If Ag-specific IFN-gamma and/or IL-4 as well as lymphoproliferative (LP) responses were found with the lack of a detectable IL-2 response, then protection was not observed. Immunity correlated with the magnitude of Nab responses, beta-chemokines and as well as balanced, qualitative T-helper responses.

AIDS Vaccines↗

Comparison of DNA probe technology and automated continuous-monitoring blood culture systems in the detection of neonatal bacteremia.

OBJECTIVE: The present study assessed the ability of a rapid chemiluminescent DNA probe assay to detect bacterial growth in blood culture specimens before their detection by continuous-monitoring blood culture (CMBC) systems. STUDY DESIGN: Three newborn intensive care units, which are members of the National Institute of Child Health and Human Development Neonatal Research Network, participated in this study. Each center employs an automated CMBC system against which the DNA probe was compared. A total of 1700 blood cultures were analyzed. A 3-ml aliquot of culture medium was removed from each culture during early incubation, processed, and analyzed by the DNA probe. RESULTS: Of 1700 blood cultures, 130 (7.6%) were detected positive by a CMBC system. Coagulase-negative staphylococci (CNS) were present in 90 (69%) of the positive cultures, and 26 (29%) were detected by the DNA probe. Other organisms accounted for the remaining 40 positive cultures, and 31 (78%) of these were detected by the probe assay. Seventy-six percent of all positive cultures were detected by a CMBC system within 24 hours. Ninety-eight percent of all positive cultures were detected by a CMBC system within 48 hours. Of the two organisms that grew in a CMBC system beyond 48 hours, both were CNS and one of these was considered a contaminant. Therefore, 99% of clinically significant organisms were detected by a CMBC system within 48 hours. CONCLUSION: This DNA probe is not sufficiently sensitive to be clinically useful; however, automated CMBC systems are sufficiently sensitive to aid in clinical decision-making regarding the continuance or discontinuance of antibiotic therapy following 48 hours of culture incubation.

Bacteremia↗

An adenylyl cyclase that functions during late development of Dictyostelium.

A variety of extracellular signals lead to the accumulation of cAMP which can act as a second message within cells by activating protein kinase A (PKA). Expression of many of the essential developmental genes in Dictyostelium discoideum are known to depend on PKA activity. Cells in which the receptor-coupled adenylyl cyclase gene, acaA, is genetically inactivated grow well but are unable to develop. Surprisingly, acaA(-) mutant cells can be rescued by developing them in mixtures with wild-type cells, suggesting that another adenylyl cyclase is present in developing cells that can provide the internal cAMP necessary to activate PKA. However, the only other known adenylyl cyclase gene in Dictyostelium, acgA, is only expressed during germination of spores and plays no role in the formation of fruiting bodies. By screening morphological mutants generated by Restriction Enzyme Mediated Integration (REMI) we discovered a novel adenylyl cyclase gene, acrA, that is expressed at low levels in growing cells and at more than 25-fold higher levels during development. Growth and development up to the slug stage are unaffected in acrA(-) mutant strains but the cells make almost no viable spores and produce unnaturally long stalks. Adenylyl cyclase activity increases during aggregation, plateaus during the slug stage and then increases considerably during terminal differentiation. The increase in activity following aggregation fails to occur in acrA(-) cells. As long as ACA is fully active, ACR is not required until culmination but then plays a critical role in sporulation and construction of the stalk.

Adenylyl Cyclases↗