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Biomedical subjects

B A King

Publications and source records attributed to B A King.

At least 19 recordsLinked to original sources
PubMed2004

Pneumococcal meningitis in Western Australian children: epidemiology, microbiology and outcome.

OBJECTIVES: Pneumococcal meningitis is now vaccine-preventable but continues to cause high rates of neurological sequelae internationally. Population-based epidemiology, outcome and microbiology data are necessary to target vaccination strategies. This study outlines these key areas for Western Australian children diagnosed 1990-2000. METHODS: The charts of all rural and metropolitan children with International Classification of Disease 9 and 10 discharge codes of pneumococcal or streptococcal meningitis from the Health Department's Hospital Morbidity Data System were reviewed. RESULTS: Over 10.5 years, 94 episodes were confirmed. The average annual incidence for children under 2 years was 13.45 per 100 000 and 0.66 per 100 000 for children 2 years or older. Indigenous children had an almost seven-fold increased risk compared to non-Indigenous (with 78.55 per 100 000 in the under two-year Indigenous group). Eight children died and 24 of the survivors had neurological sequelae. Penicillin resistance occurred in four of 87 isolates. One quarter of the cohort qualify under the current Australian policy of vaccination of high-risk children with seven-valent conjugate (7vPCV) vaccine. Most isolates (49/58) were 7vPCV serotypes, however, Indigenous populations were less well-covered (58.3% covered vs 91.3% of isolates from non-Indigenous children). Indigenous coverage would be improved to 75% with 11-valent conjugate vaccine. CONCLUSIONS: Indigenous children and those under 2 years are most affected by pneumococcal meningitis and remain primary vaccination targets. Three quarters of these children would not be protected by a policy of vaccination of only high-risk children with 7vPCV--improved protection requires higher valencies for Indigenous populations and universal infant vaccination.

Adolescent↗
PubMed2004

Pneumococcal meningitis: clinical course and resource use in Western Australian children.

OBJECTIVES: Paediatric pneumococcal meningitis causes high rates of neurological sequelae and is presenting challenges due to the emergence of antibiotic resistance. Diagnosis can be difficult and management is frequently complicated and resource intensive. This population-based study outlines the diagnosis, clinical course and initial resource use of Western Australian (WA) children diagnosed between 1990 and 2000. METHODS: The charts of all rural and metropolitan children discharged from all WA hospitals with International Classification of Disease 9 and 10 codes of pneumococcal or streptococcal meningitis from the Health Department's Hospital Morbidity Data System were reviewed retrospectively. RESULTS: Ninety-four episodes of pneumococcal meningitis were confirmed (median age 12.4 months). Initial diagnosis was often difficult with a suggestive prodrome in less than one quarter of cases and a median of two reviews until diagnosis (range 1-7). The median duration of hospitalization was 11.6 days, 41.5% were admitted to the Intensive Care Unit (ICU), and 47.9% had seizures. There were eight related deaths and neurological sequelae occurred in 24. Initial hospitalization cost on average $A 19,900. Penicillin resistance was first noted in 1993 and occurred in 4.6% of isolates. Most cases (84.5%) were caused by serotypes contained in the currently available seven-valent conjugate vaccine. CONCLUSIONS: Pneumococcal meningitis is often difficult to diagnose, necessitates long and frequently complicated in-patient stays and has high rates of neurological sequelae. It is possible to prevent most cases with new conjugate vaccines.

Adolescent↗
PubMed2003

Adverse skin and joint reactions associated with oral antibiotics in children: the role of cefaclor in serum sickness-like reactions.

OBJECTIVE: To review presentations to Princess Margaret Hospital Emergency Department (PMH ED) with adverse joint and skin reactions associated with the use of oral antibiotics, to describe the clinical course of children with cefaclor-related serum sickness-like reactions (cefaclor SSLR) and compare these with cases reported to the Adverse Drug Reactions Advisory Committee (ADRAC). METHODS: Twelve-month retrospective review of presentations to a tertiary paediatric ED (42,000 visits annually) via an ED computer database search and review of medical charts of children presenting with joint or skin reactions. Telephone interviews were conducted with the caregivers of children with cefaclor SSLR. RESULTS: Adverse skin or joint reactions occurred in 150 children; 70 after cefaclor alone, 10 after cefaclor in combination with other antibiotics and 70 after other antibiotic courses. SSLR occurred in 44 children; 32 after cefaclor alone, five after cefaclor in combination with other antibiotics and seven after other single antibiotics. In children with cefaclor SSLR, otitis media was the most common indication (59.4%), another 18.8% had viral illnesses. Prolonged sequelae occurred in four children, a situation not previously reported. Sixty reports of paediatric cefaclor SSLR were made to ADRAC during the study period, none originated from PMH ED. CONCLUSIONS: Cefaclor was associated with 53.3% of oral antibiotic related skin and joint adverse reactions and 84.1% of SSLR. The indications for its use in paediatric illness require careful reconsideration. ADRAC data under-represents the incidence of cefaclor SSLR.

Administration, Oral↗
PubMed2001

Spatially localized generation of nucleotide sequence-specific DNA damage.

Psoralens linked to triplex-forming oligonucleotides (psoTFOs) have been used in conjunction with laser-induced two-photon excitation (TPE) to damage a specific DNA target sequence. To demonstrate that TPE can initiate photochemistry resulting in psoralen-DNA photoadducts, target DNA sequences were incubated with psoTFOs to form triple-helical complexes and then irradiated in liquid solution with pulsed 765-nm laser light, which is half the quantum energy required for conventional one-photon excitation, as used in psoralen + UV A radiation (320-400 nm) therapy. Target DNA acquired strand-specific psoralen monoadducts in a light dose-dependent fashion. To localize DNA damage in a model tissue-like medium, a DNA-psoTFO mixture was prepared in a polyacrylamide gel and then irradiated with a converging laser beam targeting the rear of the gel. The highest number of photoadducts formed at the rear while relatively sparing DNA at the front of the gel, demonstrating spatial localization of sequence-specific DNA damage by TPE. To assess whether TPE treatment could be extended to cells without significant toxicity, cultured monolayers of normal human dermal fibroblasts were incubated with tritium-labeled psoralen without TFO to maximize detectable damage and irradiated by TPE. DNA from irradiated cells treated with psoralen exhibited a 4- to 7-fold increase in tritium activity relative to untreated controls. Functional survival assays indicated that the psoralen-TPE treatment was not toxic to cells. These results demonstrate that DNA damage can be simultaneously manipulated at the nucleotide level and in three dimensions. This approach for targeting photochemical DNA damage may have photochemotherapeutic applications in skin and other optically accessible tissues.

Base Sequence↗
PubMed1999

The magnitude and duration of ambulatory blood pressure reduction following acute exercise.

The purpose of this study was to observe the magnitude and duration of the ambulatory blood pressure (BP) reduction following exercise and to identify the peak intervals of BP reduction throughout the 24-h diurnal period. Subjects were 25 normo- (N = 116.7/ 78.2+/-10.0/7.2 mm Hg) and 21 hypertensive (H = 140.8/96.9+/-13.9/9.6 mm Hg) adults. Twenty-four hour ambulatory blood pressures (SBP = systolic and DBP = diastolic) were recorded following exercise (E = 50 min @ 50% VO2 max) and during a non-exercise control day (C). The 24-h pressures were compared between the E and C days for (1) duration and magnitude of the BP reduction following exercise, and for (2) the time of day for the diurnal patterns to exhibit reductions in BP. No BP differences were found for N between E and C days. Significant reductions in BP were found for 24-h average SBP (decrease 6.8 mm Hg) and DBP (decrease 4.1 mm Hg), daytime (06.00-22.00 hrs) SBP (decrease 6.9 mm Hg) and DBP (decrease 3.3 mm Hg), and sleep (22.00-06.00) SBP (decrease 5.1 mm Hg) and DBP (decrease 4.4 mm Hg) for H subjects only. H also demonstrated an 11 h reduction in SBP (chi = decrease 8.3+/-2.2 mm Hg) and 4h reduction in DBP (chi = decrease 6.0+/-1.7 mm Hg) following exercise. For the diurnal variation, the peak interval of reduction in SBP (chi = 17.0+/-2.6 mm Hg) was for 11 h; from 11.00-21.00 hrs. For DBP, a significant reduction (chi = decrease 5.7+/-0.7 mm Hg) was found for 5 h; from 11.00-15.00 h. Thus, exercise reduces both systolic and diastolic BP for a significant length of time postexercise as well as reduces pressures during the time of day that typically exhibits higher diurnal pressures.

Adult↗
PubMed1997

Crystal structure and photodynamic behavior of the blue emission variant Y66H/Y145F of green fluorescent protein.

The crystal structure of a blue emission variant (Y66H/Y145F) of the Aequorea victoria green fluorescent protein has been determined by molecular replacement and the model refined. The crystallographic R-factor is 18.1% for all data from 20 to 2.1 A, and the model geometry is excellent. The chromophore is non-native and is autocatalytically generated from the internal tripeptide Ser65-His66-Gly67. The final electron density maps indicate that the formation of the chromophore is complete, including 1,2 dehydration of His66 as indicated by the planarity of the chromophore. The chromophore is in the cis conformation, with no evidence for any substantial fraction of the trans configuration or uncyclized apoprotein, and is well-shielded from bulk solvent by the folded protein. These characteristics indicate that the machinery for production of the chromophore from a buried tripeptide unit is not only intact but also highly efficient in spite of a major change in chromophore chemical structure. Nevertheless, there are significant rearrangements in the hydrogen bond configuration around the chromophore as compared to wild-type, indicating flexibility of the active site. pH titration of the intact protein and the chromopeptide (pKa1 = 4.9 +/- 0.1, pKa2 = 12.0 +/- 0.1) suggests that the predominant form of the chromophore in the intact protein is electrically neutral. In contrast to the wild-type protein [Chattoraj, M., King, B. A., Bublitz, G. U., & Boxer, S. G. (1996) Proc. Natl. Acad. Sci. U.S.A., 8362-8367], femtosecond fluorescence up-conversion spectroscopy of the intact protein and a partially deuterated form strongly suggests that excited-state proton transfer is not coupled to fluorescence emission.

Animals↗
PubMed1997

A comparison of 24-h average blood pressures and blood pressure load following exercise.

Although the use of 24-h ambulatory blood pressure monitoring has been recommended in the study of blood pressure and exercise, consistent results have not been found for average 24-h systolic or diastolic blood pressures. Systolic load and diastolic load (the percentage of pressures >140/90 mm Hg during daytime hours and >120/80 mm Hg during sleep) have recently been identified as an important variable, but has had limited use with exercise. The purpose of this study was to compare the average systolic and diastolic pressures to systolic and diastolic loads from 24-h data recorded after a 50-min treadmill walk at 50% VO2max to data from a nonexercise control day. Subjects were 36 normotensive (116.9 +/- 10.7/77.0 +/- 8.9 mm Hg) and 25 hypertensive (141.0 +/- 13.7/96.6 +/- 9.0 mm Hg) adults. No significant differences were found for systolic and diastolic pressures or loads between the control and exercise days for normotensives. Even though no significant changes were found for any of the average systolic and diastolic pressures between the control and exercise days for the hypertensives, significant reductions were found in systolic load for 24-h (-25.7%), day (6 AM to 10 PM, -23.1%), work (6 AM to 5 PM, -22.9%), and leisure (5 PM to 10 PM, -26.7%) periods; and in diastolic load for the work (-22.5%) period. Thus, the measurement of systolic and diastolic load may be more sensitive than average systolic and diastolic blood pressures for the detection of 24-h ambulatory blood pressure changes with exercise in borderline hypertension.

Adult↗
PubMed1997

Effect of exercise on milk immunoglobulin A.

The major immunoglobulin (Ig) in human secretions is IgA. The immune properties of breast milk are well documented; however, the immunological influence of maximal exercise has not been established. The objective of this study was to investigate the role that exercise has on breast milk IgA and IgA subclasses. Breast milk was collected from 17 lactating women (4.6 +/- 2.3 months postpartum) before and after randomized exercise and control periods. The exercise treatment was a maximal graded treadmill test (VO2max = 30.3 +/- 5.7 mL x min-1 x kg-1). Milk was collected at rest, the breasts were emptied, and samples obtained 10, 30, and 60 min following either exercise or 30-min control rest periods. IgA concentrations were established by enzyme-linked immunosorbent assay. The results indicated that samples taken 10 and 30 min after the exercise period had significantly lower (P < or = 0.05) milk IgA concentrations (21.0 +/- 1.8 and 21.8 +/- 1.4 microg x mL-1, respectively) than the corresponding control resting samples (52.8 +/- 3.5 and 79.3 +/- 7.7 microg x mL-1). The exercise samples were similar to the control samples at 60 min (134.0 +/- 24.6 and 116.0 +/- 15.4 microg x mL-1, respectively), indicating that by 1 h, milk IgA production had recovered. The IgA1 data showed a similar significant decrease (P < or = 0.05) at 10 min postexercise, which also returned to control concentrations by the 30- and 60-min collection intervals. There was no significant change in the milk IgA2 concentrations at any of the time points studied. Milk IgA concentrations increased significantly in both exercise and resting control groups after the breasts were emptied, suggesting that breast emptying stimulated milk IgA synthesis. The results provide evidence that exercise alters milk IgA and IgA1 concentrations for 10-30 min after exhaustive exercise, but recovers by 1 h, and provide additional support for exercise effects on the mucosal immune system.

Adult↗
PubMed1996

Ultra-fast excited state dynamics in green fluorescent protein: multiple states and proton transfer.

The green fluorescent protein (GFP) of the jellyfish Aequorea Victoria has attracted widespread interest since the discovery that its chromophore is generated by the autocatalytic, posttranslational cyclization and oxidation of a hexapeptide unit. This permits fusion of the DNA sequence of GFP with that of any protein whose expression or transport can then be readily monitored by sensitive fluorescence methods without the need to add exogenous fluorescent dyes. The excited state dynamics of GFP were studied following photo-excitation of each of its two strong absorption bands in the visible using fluorescence upconversion spectroscopy (about 100 fs time resolution). It is shown that excitation of the higher energy feature leads very rapidly to a form of the lower energy species, and that the excited state interconversion rate can be markedly slowed by replacing exchangeable protons with deuterons. This observation and others lead to a model in which the two visible absorption bands correspond to GFP in two ground-state conformations. These conformations can be slowly interconverted in the ground state, but the process is much faster in the excited state. The observed isotope effect suggests that the initial excited state process involves a proton transfer reaction that is followed by additional structural changes. These observations may help to rationalize and motivate mutations that alter the absorption properties and improve the photo stability of GFP.

Amino Acid Sequence↗
PubMed1994

Finger-movement tracking scores in healthy subjects.

The purpose of this study was to examine the effects of age, sex, and hand preference on precise control of voluntary movement at the index finger metacarpophalangeal joint in able-bodied volunteers. An electrogoniometer was attached to this joint and connected to a computer. The computer screen displayed a sine wave target that each subject attempted to track with careful extension and flexion finger movements. Accuracy index scores were calculated for the extension phases, flexion phases, and the total sine wave. Each subject performed three tracking trials and the average for each of the above scores was computed. The results showed that younger subjects tracked significantly more accurately than older subjects and men tracked significantly more accurately than women. Also, the subjects tracking with the nonpreferred hand (15 right, 105 left) tracked significantly more accurately than those subjects tracking with the preferred hand (112 right, 8 left) in the flexion phases of the test. The data from these able-bodied subjects provide a base for comparison of patients' data, which may be helpful in the early recognition and monitoring of problems with precision in movement control.

Adult↗