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Biomedical subjects

T Nolan

Publications and source records attributed to T Nolan.

At least 19 recordsLinked to original sources

A combined liquid Hib (PRP-OMPC), hepatitis B, diphtheria, tetanus and whole-cell pertussis vaccine: controlled studies of immunogenicity and reactogenicity.

We evaluated the immunogenicity and reactogenicity of a new liquid pentavalent combination vaccine, which incorporates a diphtheria, tetanus and whole-cell pertussis vaccine (DTP) with Hib (PRP-OMPC) and hepatitis B vaccine (HB), in a series of three studies involving 2156 infants. The vaccination schedule was 2, 4, 6 and 18 months for all studies. In addition, subjects in the third study also received a dose of monovalent hepatitis B vaccine at birth. The principal study was a randomised double blind trial of two separate, but concurrently administered vaccines in each of three groups: pentavalent vaccine [DTP-Hib-HB] plus placebo (Group A, n=619); quadrivalent vaccine [DTP-HB] plus Hib vaccine (Group B, n=620); and bivalent vaccine [Hib-HB] plus DTP (Group C, n=226). The second study (Group D, n=231) was an open trial of three separate, but concurrently administered licensed control vaccines (DTP, Hib and HB). The third study (Group E, n=460) administered a dose of monovalent hepatitis B vaccine at birth followed by pentavalent vaccine as for Group A. Subjects were bled prior to the 2- and 18-month vaccinations, and a month after the 6- and 18-month vaccinations. A diary card was used to record subject temperatures and other systemic and local clinical signs for 7 days after each vaccination. The pentavalent vaccine, whether or not preceded by a birth dose of hepatitis B vaccine, was generally well tolerated at all administration times, and had a reactogenicity profile similar to that observed for licensed vaccine controls. Diphtheria and tetanus antibody levels were substantially above protective levels in all study groups. The anti-HBs responses (% > or = 10 mIU/ml) following the 6-month dose of vaccines were, respectively, for Groups A-E: 83.2, 91.7, 96.5, 98.8 and 93.9%, and following the 18-month doses: 87.9, 97.5, 98.8, 98.8 and 92.8%. Anti-PRP responses (% > or = 1.0 microg/ml) following the 6-month dose for Groups A-D were 86.0, 90.5, 91.2, and 74.4%, and after the 18-month dose for Groups A-E were 97.3, 98.3, 98.1, 97.0, and 99.5%. Consistently higher geometric mean titres (GMTs) for pertussis antibodies to agglutinogens (Agg2, Agg3) and pertactin were recorded for the pentavalent vaccine compared to the licensed control vaccine, though they were somewhat lower for pertussigen (PT). Except for the hepatitis B response, antibody responses induced by the pentavalent vaccine to all antigens with a schedule commencing at 2 months of age and completed at 18 months were equivalent to responses to the same antigens induced by the separate, but concurrently administered licensed control vaccines. A regimen of a birth dose of hepatitis B vaccine followed by pentavalent vaccine at 2, 4, 6 and 18 months was not countered by any clinically significant decrease in seroresponses.

Age Factors↗

Quality of hospital care for seriously ill children in less-developed countries.

BACKGROUND: Improving the quality of care for sick children referred to hospitals in less-developed countries may lead to better outcomes, including reduced mortality. Data are lacking, however, on the quality of priority screening (triage), emergency care, diagnosis, and inpatient treatment in these hospitals, and on aspects of these potential targets that would benefit most from interventions leading to improved health outcomes. METHODS: We did a qualitative study in 13 district hospitals and eight teaching hospitals in seven less-developed countries. Experienced paediatricians used a structured survey instrument to assess initial triage, emergency and inpatient care, staff knowledge and practices, and hospital support services. FINDINGS: Overall quality of care differed between countries and among hospitals and was generally better in teaching hospitals. 14 of 21 hospitals lacked an adequate system for triage. Initial patient assessment was often inadequate and treatment delayed. Most emergency treatment areas were poorly organised and lacked essential supplies; families were routinely required to buy emergency drugs before they could be given. Adverse factors in case management, including inadequate assessment, inappropriate treatment, and inadequate monitoring occurred in 76% of inpatient children. Most doctors in district hospitals, and nurses and medical assistants in teaching and district hospitals, had inadequate knowledge and reported practice for managing important childhood illnesses. INTERPRETATION: Strengthening care for sick children referred to hospital should focus on achievable objectives with the greatest potential benefit for health outcome. Possible targets for improvement include initial triage, emergency care, assessment, inpatient treatment, and monitoring. Priority targets for individual hospitals may be determined by assessing each hospital.

Adolescent↗

Risk-factors for meningococcal disease in Victoria, Australia, in 1997.

In Victoria between 1990 and 1996, meningococcal infections occurred in 1-2/100,000 people each year, with sometimes devastating outcome. In 1997, a typical year, we conducted a case-control study of all cases notified to the State Disease Control Unit, to investigate personal, environmental and lifestyle risk factors. In bivariate analysis many exposures were statistically significantly different (at P = 0.01) in cases and controls. The level of risk, and specific risks, differed between children (under 16) and adults (16 years and over). In multivariate analysis few exposures remained significant (at P = 0.05). However, these included having a smoker amongst close contacts, exposure to construction dust, recent illness, a history of snoring and speech problems, and sharing a bedroom. Besides confirming some previously identified risk factors, this is the first time that snoring and speech problems have been identified as risk factors for meningococcal disease.

Adolescent↗

Laboratory enhanced surveillance for meningococcal disease in Victoria.

OBJECTIVE: To describe the epidemiological and microbiological characteristics and notification patterns of invasive meningococcal disease (IMD) in Victoria between 1990 and 1999. METHODS: Cases of IMD occurring between 1990 and 1995 identified in any of three databases were combined, matching where possible. Statistical modelling provided estimates of cases missing from all datasets. Notification sources for 1999 and 2000 cases were identified. Cases identified from notification and laboratory results provided the data to describe IMD epidemiology between 1990 and 1999. RESULTS: Between 1990 and 1995, 479 cases of IMD were identified. Three individual datasets each identified between 62 and 82% of cases and 47% of cases were identified in all three datasets. Statistical modelling estimated that between 37 and 83 additional cases were not identified by any dataset. Serogroup B and C strains caused 63 and 33% of culture-positive cases, respectively, with a substantial rise in serogroup C cases in 1999. Epidemiological characteristics remained relatively constant between 1990 and 1998, but an increase in patient age was seen in cases with serogroup C disease in 1999. In addition to three clonal strains seen elsewhere, an additional strain was identified that was unique to Victoria. Since January 1999, only 72% of notifications have come from treating doctors. CONCLUSIONS: Meningococcal disease is of increasing public health significance in Victoria. Laboratory enhanced notification has improved case identification and detailed microbiological information has improved our understanding of the changing epidemiology of this disease. Collaboration with laboratories and other agencies, active investigation of putative cases and microbiological monitoring are important elements in supporting public health decisions about the control of IMD.

Age Distribution↗

Hypercapnia related to a faulty adult co-axial breathing circuit.

IMPLICATIONS: This report describes the appearance of CO2 on the capnograph during inspiration, which was linked to disconnection of the inner tube of a coaxial circuit extension piece. The increased use of coaxial breathing systems for adults makes inner tubes disconnections an important consideration when the CO2 appears during inspiration.

Anesthesia, Closed-Circuit↗

Adolescent hepatitis B immunisation--should it be the law?

Universal hepatitis B immunisation of young adolescents was included in the Australian Standard Vaccination Schedule in 1998. However, rates of immunisation among adolescents world-wide have often been inadequate. Australia's experience in this area is no exception, particularly in States where school-based delivery is not carried out. Legislation for pre-school immunisation certification currently exists in several States and this legislation is distinctly different from the compulsory or mandatory immunisation that exists in several other developed countries. There have been demonstrable gains in uptake as a result of mandatory immunisation requirements in the United States and there is evidence to suggest that immunisation certification in Australia has also been beneficial. However, it is important to recognise that both certification and mandatory immunisation legislation have inherent difficulties. In this paper, we argue that legislation for high school immunisation certification, as part of a multi-faceted vaccine delivery strategy tailored to adolescents, is required to achieve the uptake that will lead to interruption of transmission of the hepatitis B virus in Australia. Not only will it substantially reduce incident cases of hepatitis B for the next decade, it will also provide a framework for the successful introduction of future adolescent vaccine initiatives in Australia.

Adolescent↗

Respiratory distress syndrome and birth order in premature twins.

OBJECTIVE: To determine the effect of birth order on respiratory distress syndrome (RDS) in the outcome of twins in a large premature population managed in a modern neonatal intensive care unit. METHODS: An historical cohort study design was used to analyse the neonatal outcomes of 301 premature liveborn twin sibling pairs of between 23 and 31 weeks gestation from the Australia and New Zealand Neonatal Network 1995 database. RESULTS: Among the 56 twin sibling pairs who were discordant for RDS, the second twin was affected in 41 cases (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.5 to 5.3). The excess risk of RDS in the second twin increased with gestation and was statistically significant for twins above 29 weeks gestation (OR 4.4, 95% CI 1.6 to 15). CONCLUSIONS: There is a significant increased risk of RDS associated with being the second born of premature twins, which appears to depend on gestation.

Birth Order↗

Global cDNA amplification combined with real-time RT-PCR: accurate quantification of multiple human potassium channel genes at the single cell level.

We have developed a sensitive quantitative RT-PCR procedure suitable for the analysis of small samples, including single cells, and have used it to measure levels of potassium channel mRNAs in a panel of human tissues and small numbers of cells grown in culture. The method involves an initial global amplification of cDNA derived from all added polyadenylated mRNA followed by quantitative RT-PCR of individual genes using specific primers. In order to facilitate rapid and accurate processing of samples, we have adapted the approach to allow use of TaqMan real-time quantitative PCR. We demonstrate that the approach represents a major improvement over existing conventional and real-time quantitative PCR approaches, since it can be applied to samples equivalent to a single cell, is able to accurately measure expression levels equivalent to less than 1/100th copy/cell (one specific cDNA molecule present amongst 10(8) total cDNA molecules). Furthermore, since the initial step involves a global amplification of all expressed genes, a permanent cDNA archive is generated from each sample, which can be regenerated indefinitely for further expression analysis.

Breast↗

Stable germline transformation of the malaria mosquito Anopheles stephensi.

Anopheline mosquito species are obligatory vectors for human malaria, an infectious disease that affects hundreds of millions of people living in tropical and subtropical countries. The lack of a suitable gene transfer technology for these mosquitoes has hampered the molecular genetic analysis of their physiology, including the molecular interactions between the vector and the malaria parasite. Here we show that a transposon, based on the Minos element and bearing exogenous DNA, can integrate efficiently and stably into the germ line of the human malaria vector Anopheles stephensi, through a transposase-mediated process.

Animals↗

Toward Anopheles transformation: Minos element activity in anopheline cells and embryos.

The ability of the Minos transposable element to function as a transformation vector in anopheline mosquitoes was assessed. Two recently established Anopheles gambiae cell lines were stably transformed by using marked Minos transposons in the presence of a helper plasmid expressing transposase. The markers were either the green fluorescent protein or the hygromycin B phosphotransferase gene driven by the Drosophila Hsp70 promoter. Cloning and sequencing of the integration sites demonstrated that insertions in the cell genome occurred through the action of Minos transposase. Furthermore, an interplasmid transposition assay established that Minos transposase is active in the cytoplasmic environment of Anopheles stephensi embryos: interplasmid transposition events isolated from injected preblastoderm embryos were identified as Minos transposase-mediated integrations, and no events were recorded in the absence of an active transposase. These results demonstrate that Minos vectors are suitable candidates for germ-line transformation of anopheline mosquitoes.

Animals↗

Continuous quality improvement for patients with back pain.

Recent evidence has changed traditional approaches to low back pain, suggesting minimal bed rest, highly selective imaging, and early return to normal activities. However, there are wide geographical variations in care, and substantial gaps between practice and evidence. This project sought to merge scientific evidence about back pain and knowledge about behavior change to help organizations improve care for back pain. Participating insurance plans, HMOs, and group practices focused on problems they themselves identified. The year-long program included quarterly meetings, coaching for rapid cycles of change, a menu of potential interventions, and recommendations for monitoring outcomes. Participants interacted through meetings, e-mail, and conference calls. Of the 22 participating organizations, 6 (27%) made major progress. Typical changes were reduced imaging, bed rest, and work loss, and increased patient education and satisfaction. Specific examples were a 30% decrease in plain x-rays, a 100% increase in use of patient education materials, and an 81% drop in prescribed bed rest. Despite the complexity of care for back pain, rapid improvements appear feasible. Several organizations had major improvements, and most experienced at least modest improvements. Key elements of successful programs included focus on a small number of clinical goals, frequent measurement of outcomes among small samples of patients, vigilance in maintaining gains; involvement of office staffs as well as physicians, and changes in standard protocols for imaging, physical therapy, and referral.

Back Pain↗

Randomised controlled trial of an educational strategy to increase school-based adolescent hepatitis B vaccination.

OBJECTIVES: This study aimed to evaluate a specifically designed hepatitis B education/promotion curriculum package as part of a successful hepatitis B vaccination delivery system to adolescents. METHODS: A randomised-controlled trial was used to evaluate the effect of the curriculum package (or intervention) on uptake of vaccine. Schools were randomly selected from the metropolitan region of Melbourne to intervention (66 schools or 7,588 students) or control groups (69 schools or 9,823 students). Class teachers administered the intervention to students over 4 class periods before the vaccination course. RESULTS: The difference in mean school uptake between intervention and control was small at 1-2% per dose. 95% confidence intervals around the differences were -5% to 2% per dose and not significant. Intervention schools taught an average of 7 items out of 12 from the curriculum package. Immunisation rates increased by 4-10% per dose between low and high implementation schools, but this trend was not significant. Impact evaluation demonstrated significantly greater knowledge of hepatitis B and vaccination among students in the intervention than the control group. CONCLUSION: Hepatitis B vaccination of pre-adolescents was not increased by the implementation of a curriculum package that successfully increased knowledge and awareness of hepatitis B in a school-based vaccination program. Additional strategies directed at the education of parents, the cooperative role of schools and pro-active providers might also be required to maximise vaccine uptake in this age group.

Adolescent↗

Twelve year outcomes following bacterial meningitis: further evidence for persisting effects.

AIM: To determine whether intellectual and cognitive impairments observed seven years following early childhood bacterial meningitis persist into adolescence. METHODS: Blinded neuropsychological, auditory, and behaviour assessments were conducted in 109 (69%) subjects from an original cohort of 158 children, seven and 12 years after their meningitis, and in 96 controls. RESULTS: Meningitis subjects remained at greater risk than controls for any disability (odds ratio OR 4.7, confidence interval 2.2 to 9.6). Those with acute neurological complications had more sequelae than children with uncomplicated meningitis or controls (47% v 30% v 11.5% respectively; p < 0.001). Differences in intellectual, academic, and high level cognitive function between subjects and controls were maintained at the seven and 12 year assessments. In contrast, lower order skills improved, while behaviour scores deteriorated significantly (p = 0.033). CONCLUSIONS: Many of the deficits identified at the seven year follow up persist 12 years after an episode of bacterial meningitis.

Adolescent↗

Oral absorption of clarithromycin in acute illness and during convalescence in patients with community-acquired pneumonia.

STUDY OBJECTIVE: To compare the extent of oral clarithromycin absorption in patients during an illness and in health. DESIGN: Sequential two-phase prospective study including an acutely ill pneumonia phase (PP) and a subsequent convalescent phase (CP). STUDY POPULATION: Patients >/= 18 years old with radiographically confirmed community-acquired pneumonia (CAP) who were admitted to the hospital. METHODS: During both study phases, patients received one single 500-mg dose of oral clarithromycin. Serial blood samples were drawn over a 24-h period in order to characterize the plasma concentration-time curves. Area under the curve from zero to 24 h (AUC(0-24)), maximum plasma concentration (Cmax), and time to maximum concentration (Tmax) were determined for both clarithromycin and its metabolite, 14-hydroxyclarithromycin, and compared between the two phases. RESULTS: Twelve patients completed both phases of the study. For clarithromycin, there was a significant increase AUC(0-24) (47.37 +/- 8.51 microg/h/mL vs 36.22 +/- 6.09 microg/h/mL) in favor of the PP. There were no significant differences detected with respect to Cmax (4.32 +/- 0.63 microg/mL vs 3.57 +/- 0.46 microg/mL), or Tmax (3.50 +/- 0.50 h vs 2.83 +/- 0.59 h) between PP and CP. For 14-hydroxyclarithromycin, the AUC(0-24) and Cmax were significantly higher (5.84 +/- 1.08 microg/h/mL vs 8.84 +/- 1.92 microg/h/mL; 0.42 +/- 0.08 microg/mL vs 0.76 +/- 0.23 microg/mL) in the CP as compared to the PP. Tmax remained unchanged. CONCLUSION: The extent of absorption of oral clarithromycin was not diminished during an acute illness with CAP.

Absorption↗

Growth of the genital primordium as a marker to describe a time course for the heterogonic larval development in Strongyloides stercoralis.

A time course for the heterogonic development of Strongyloides stercoralis is described and a method for distinguishing the early larval stages of this nematode is proposed. The number of cells in the developing gonad were counted at various time intervals of incubation, along with the percentage of larvae in molt at each interval. The time course of growth of the gonad follows a pattern comparable to that reported for body length in an idealized general nematode. A model for the heterogonic development of S. stercoralis is proposed, which, although similar to other nematode developmental models, is stage specific for S. stercoralis, allowing the otherwise morphologically similar rhabditiform stages (L1, L2) to be distinguished.

Animals↗