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Biomedical subjects

T Nolan

Publications and source records attributed to T Nolan.

At least 37 records · Page 2Linked to original sources

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↗

Sparfloxacin versus ciprofloxacin for the treatment of community-acquired, complicated skin and skin-structure infections.

Fluoroquinolones have been shown to be effective in the treatment of complicated skin and skin-structure infections, in part because of their broad-spectrum antibacterial activity against causative pathogens that are resistant to older antimicrobial agents. We enrolled 603 adult patients (>58% male, >85% white) in a double-masked, double-dummy, randomized, multicenter trial to compare the efficacy and tolerability of sparfloxacin (400-mg loading dose followed by 200 mg once daily) with those of ciprofloxacin (750 mg twice daily) for 10 days in the treatment of community-acquired, complicated skin and skin-structure infections. The primary efficacy variable was clinical response, based on assessment of signs and symptoms, in the clinically assessable population. Patients in the sparfloxacin and ciprofloxacin groups were comparable with respect to demographic characteristics, underlying diseases, medical history, and laboratory test results. Wound infection was the most common diagnosis, and Staphylococcus aureus was the most frequently isolated pathogen. For the 475 clinically assessable patients, the clinical success rate (percentage of patients cured or improved) was 90.1% (210/233) with sparfloxacin and 87.2% (211/242) with ciprofloxacin. In this analysis (95% confidence interval [CI], -2.8 to 8.6) and the intent-to-treat analyses (95% CI, -4.2 to 6.2), results with sparfloxacin were statistically equivalent to those with ciprofloxacin (95% CI, -1 to 15.3). For bacteriologically assessable patients, eradication rates were 87.0% (141/162) with sparfloxacin and 79.9% (123/154) with ciprofloxacin (95% CI, -1 to 15.3). Eradication rates of S. aureus and coagulase-negative staphylococcal infections were 90.2% (101/112) with sparfloxacin and 77.9% (88/113) with ciprofloxacin. For patients with 2 or more pathogens at baseline (mixed infections), bacteriologic success was 87.6% for sparfloxacin and 77.9% for ciprofloxacin. Pseudomonas aeruginosa infections were eradicated or presumed eradicated in 71.4% (10/14) of sparfloxacin-treated patients and 87.5% (7/8) of ciprofloxacin-treated patients. Overall success rates in the bacteriologically assessable patients for sparfloxacin (84.6% [137/162]) and ciprofloxacin (78.6% [121/154]) were statistically equivalent (95% CI, -2.5 to 14.5). Tolerability was assessed in all patients who received study medication. The overall frequency of treatment-related adverse events was comparable in the 2 treatment groups (26.5% sparfloxacin, 23.3% ciprofloxacin). Drug-related adverse events involving the digestive system occurred in 7.1% of sparfloxacin-treated patients and 19.0% of ciprofloxacin-treated patients; photosensitivity reactions were reported in 11.1% of patients in the sparfloxacin group and 0.7% of patients in the ciprofloxacin group (P < 0.001). The mean change in QTc interval from baseline to the maximum on-treatment value was greater in the sparfloxacin group (9 milliseconds) than in the ciprofloxacin group (3 milliseconds) (P = 0.005; 95% CI, 0.002 to 0.010). The efficacy of sparfloxacin was comparable to that of ciprofloxacin in the treatment of community-acquired, complicated skin and skin-structure infections, including those caused by staphylococci, the most common pathogens. Sparfloxacin's once-daily regimen, high skin-tissue penetration, and improved activity against gram-positive cocci make it a therapeutic alternative to ciprofloxacin for patients who are not at risk for photosensitivity reactions or adverse events associated with prolongation of the QTc interval.

Adult↗

Immunisation uptake, services required and government incentives for users of formal day care.

OBJECTIVES: To determine immunisation uptake in children attending formal day care prior to the introduction of certificates (state) and parent incentives (federal), and to document parent and child carers' attitudes to these strategies. METHOD: In 1997, 60 child care centres and 300 family day carers in suburban Melbourne were randomly sampled. Immunisation dates, service use and preference, and views on government incentives were obtained from parents of children under three years of age. RESULTS: From 2,454 eligible children, information was obtained for 1,779, of whom 84% (95% CI 82-86) were completely immunised. Low income (OR 1.8, 95% CI 1.2-1.9, p < or = 0.001) and larger family size (OR 1.8, 95% CI 1.2-2.7, p = 0.002) and only ever using a doctor (OR 1.6, 95% CI 1.1-2.3) was associated with incomplete immunisation. Main reasons for delaying immunisation were occurrence of minor illness and work commitments. Families would prefer immunisation services at Maternal and Child Health visits (39%), evening sessions (22%) and at day care (22%). Immunisation uptake could increase to 94% if those receiving Childcare Assistance (67%) immunised their children on time but would increase to 87% if these incentive only motivated those for whom Childcare Assistance was essential (15%). While 98% of day care co-ordinators and 71% of family day care co-ordinators documented immunisation status at commencement of child care, only 51% and 33% respectively regularly updated this information. CONCLUSION: Providing client-focused, flexible immunisation services and government incentives and legislation may work together to boost immunisation levels for those in formal child care.

Adult↗

Evaluation of a national surveillance unit.

AIM: The Australian Paediatric Surveillance Unit (APSU) facilitates national active surveillance of uncommon childhood conditions. This study assessed whether it fulfilled its objectives and satisfied criteria established by the Centers for Disease Control and Prevention (CDC) for evaluating surveillance systems. METHODS: Anonymous questionnaires were sent to users of the system, individual studies were reviewed, and data were collected from independent sources. RESULTS: Seven hundred and sixty six clinicians, 48 investigators, and 15 public health professionals responded to the questionnaires. Clinicians reported that the APSU was useful, 33% saying information provided by the APSU informed or changed their clinical practice. Most (88%) reported that completing monthly report cards was not a burden. Impact on policy development was limited by suboptimal dissemination of information to public health professionals. Flexibility and timeliness were limited by design. Estimated sensitivity of APSU studies ranged from 92% (congenital rubella) to 31% (drowning/near drowning). Positive predictive value of notified cases was over 70% for most studies. CONCLUSION: The APSU fulfils most of its objectives and meets CDC criteria salient to these. Ways in which the APSU could be improved have been identified, as have methodological challenges and limitations in applying CDC guidelines to this type of unit.

Australia↗

Measles-mumps-rubella and hepatitis B vaccination uptake in adolescents: a survey in metropolitan Melbourne.

OBJECTIVE: To measure the uptake of preadolescent measles-mumps-rubella (MMR) and adolescent hepatitis B vaccinations and assess the influence of certain demographic factors on the uptake of these vaccines. DESIGN: Prevalence surveys of uptake rates of preadolescent (school Year 6; age 10-11 years) MMR and adolescent (school Year 9; age 13-14 years) hepatitis B vaccination. SETTING: City of Darebin, an inner northern metropolitan region of Melbourne, 1996. SUBJECTS: 1160 Year 6 school students (580 boys) and 1102 Year 9 school students (548 boys). INTERVENTION: School-based vaccination program administered by Darebin Council. RESULTS: 83% of Year 6 students were vaccinated with the MMR vaccine (84.1% of girls and 81.9% of boys). 71.6% of Year 9 students completed the full course of hepatitis B vaccination (68.9% of boys and 74.2% of girls). There was a higher uptake of MMR in non-government primary schools, but no other demographic factors (sex, economic status, non-English-speaking background, parental education, school class size) were associated. CONCLUSIONS: These uptake rates do not meet National Health and Medical Research Council (NHMRC) recommendations. Further study is required to determine and quantify the factors that affect vaccination uptake in adolescence. Programs may then be developed to improve vaccination uptake.

Adolescent↗

A combined liquid Hib (PRP-OMP), hepatitis B, diphtheria, tetanus and whole-cell pertussis vaccine: uncontrolled preliminary clinical trial of immunogenicity and reactogenicity.

We have conducted a preliminary uncontrolled clinical trial of the immunogenicity and reactogenicity of a new fully liquid pentavalent combination vaccination which incorporates a diphtheria, tetanus and whole-cell pertussis vaccine with Hib (PRP-OMP) and hepatitis B vaccines. Forty-five infants received three doses of the pentavalent vaccination at 2, 4, and 6 months of age, and then a fourth dose at 18 months of age. Subjects were bled prior to each vaccination, and a month after the third and fourth vaccinations. A 7-day diary card was used to record subject temperatures and other systemic and local clinical signs after each vaccination. After the third dose, 98% of subjects had anti-PRP titres above 1 microgram ml-1 (95%ci 88%, 100%). Following boosting, the geometric mean titre (GMT) rose a mean 27-fold (95%ci 19-fold, 38-fold) to 33 micrograms ml-1, and all subjects' titres (lower bound of 95%ci 92%) exceeded 1 microgram ml-1. For hepatitis B antibody, there was a GMT of 100 mIU ml-1 after the third dose, and 86% of infants (95%ci 73%, 95%) had antibody levels > or = 10 mIU ml-1. After the fourth dose, there was a mean 77-fold boost (95%ci 48-fold, 130-fold) to a GMT of 860 mIU ml-1 and 95% (95%ci 84%, 99%) of subjects had titres > or = 10 mIU ml-1. Diphtheria, tetanus, and pertussis antibody levels were all at acceptable levels after the first three doses and again after the fourth vaccination. The pentavalent vaccine was well tolerated at all administration times, and had a minor reactogenicity profile similar to DTPw alone as reported in previous studies. This study has provided preliminary evidence for both the safety and immunogenicity of the pentavalent vaccine given as a course at 2, 4, 6 and 18 months.

Antibodies, Bacterial↗

Is a paediatrician needed at all Caesarean sections?

OBJECTIVE: The need for a skilled neonatal resuscitator in the form of a paediatrician or paediatric registrar to attend a vaginal delivery or Caesarean section (CS) is not clearly defined. This study was undertaken in order to ascertain the level of resuscitation a neonate might require dependent on the delivery mode and type of anaesthesia used. METHODOLOGY: We analysed the Tasmanian Obstetric Audit from 1980 to 1989 for the need for intubation and Apgar scores at 1 min of term singleton deliveries by the mode of delivery. RESULTS: The number of singleton term deliveries was 64739. When the data were analysed annually there was a trend for a reduction in the need for intubation in CS deliveries during the first 5 years, although this was not paralleled by an improvement in Apgar scores. Thus the intubation rate data are also presented for the last 5 years of the study. The intubation rate, Apgar score at 1 min of < 4, and Apgar score at 1 min of > or = 4 < 7 for repeat CS under epidural anaesthesia were 0.55% (0.26% for 1985-89) 0.83% and 3.58%, respectively, with relative risks when compared with spontaneous normal vaginal delivery of 1.8 (1.2 for 1985-89), 0.7 and 0.5, respectively. The relative risk of these outcomes was higher than for normal vaginal delivery for all other modes of delivery including repeat CS under general anaesthesia. CONCLUSION: It is concluded that a paediatrician or paediatric registrar is not required to routinely attend repeat CS under epidural anaesthesia, but should be present for repeat CS under general anaesthesia.

Anesthesia, Obstetrical↗

Immunogenicity and reactogenicity associated with an 18-month booster dose of a new diphtheria-tetanus-whole cell pertussis vaccine.

OBJECTIVE: To establish safety and immunogenicity of a reformulated whole cell pertussis based diphtheria-tetanus-pertussis vaccine (DTPw) at the 18-month booster stage following a 2, 4, and 6-month primary immunization course. METHOD: Open trial in suburban Melbourne in 100 healthy children initially recruited through maternal and child health centres. Thirty-five subjects were bled prior to vaccination, and 4-6 weeks after vaccination. A 7-day diary card was used to record subject temperatures and other systemic and local clinical signs. RESULTS: The increase in antibody geometric mean titres (GMT) after boosting was 19.5-fold (95%ci 14.2, 27.2) for tetanus and 26.5-fold (95%ci 16.6, 42.4) for diphtheria. Pertussis antibody GMTs also all showed substantial increases following the booster, with mean fold changes in titre ranging from 7.3 (Agg2) to 31.3 (Fha). Seventeen percent of subjects (95%ci 10%, 26%) experienced axillary temperatures > or = 38 degrees C during the 24-h period following vaccination. Low rates of significant (> 25 mm) injection site redness (13%) and swelling (8%) were recorded at 24 h postvaccination. CONCLUSION: This vaccine was well tolerated by children at 18 months of age, and showed substantial boosting of antibody to all components.

Diphtheria-Tetanus-Pertussis Vaccine↗

Vaccine preventable diseases and immunisations: a qualitative study of mothers' perceptions of severity, susceptibility, benefits and barriers.

This study investigated mothers' perceptions of vaccine-preventable diseases and associated vaccines in terms of perceived susceptibility, severity, benefits and barriers. A purposive sampling strategy was used to choose mothers whose only or youngest child was completely, incompletely (behind the recommended immunisation schedule) or partially (parents chose or advised not to have a specific immunisation) immunised or had no immunisations. Semi-structured interviews found that complete immunisers believed the risk of vaccines was lower than the risk from disease and that the likelihood of contracting many of these diseases was low. Incomplete immunisers perceived vaccines to be less effective in preventing disease and were often confused about which diseases the vaccines would protect against. Non-immunisers were more concerned about unknown, long-term side effects of vaccines than the diseases. Many mothers who did immunise believed that preventing diseases was not always possible and for diseases such as measles, mumps and rubella, it was not always necessary nor desirable. Vaccines were perceived as placing stress on the immune system rather than strengthening it. Important themes relating to barriers to the decision to immunise were a lack of 'balanced', detailed information and poor communication between health providers and parents. The major barrier to timely, age-appropriate immunisations was the occurrence of minor illnesses in the target child or the family. This study found that many mothers were balancing the risks of immunising with the risks of not immunising and this must be taken into account, along with factors such as difficulties in obtaining immunisations.

Australia↗

Kawasaki disease in Australia, 1993-95.

AIM: To describe the epidemiology, management, and rate of cardiac sequelae of Kawasaki disease in Australia. DESIGN: Cases were notified to the Australian Paediatric Surveillance Unit, an active national surveillance scheme, from May 1993 to June 1995. RESULTS: 139 cases of Kawasaki disease were confirmed. In 1994, the annual incidence was 3.7/100,000 children < 5 years old. Sixteen children were not admitted to hospital. Coronary artery abnormalities were reported in 35 (25%) children. Two patients were diagnosed at postmortem examination. Sixty six per cent of patients were diagnosed within 10 days of onset and 81% of these received intravenous gammaglobulin within 10 days. Forty five of the notified children did not fulfil the study criteria because of streptococcal infection or insufficient clinical criteria. One child with streptococcal infection had coronary artery dilatation. CONCLUSION: Diagnosis of Kawasaki disease was delayed beyond 10 days in one third of patients, and almost 20% of children who could have received gammaglobulin within 10 days did not. The distinction between Kawasaki disease, streptococcal infection, and other possible diagnoses is problematic in some children.

Adolescent↗