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Biomedical subjects

R Condon

Publications and source records attributed to R Condon.

At least 19 recordsLinked to original sources

Bovine kidney tissue/biological fluid correlation for penicillin.

Penicillin is one of the most commonly misused drugs in steers and dairy cows. In the US, at slaughter the tolerance is 50 ng/g in kidney and other edible tissues. If the tolerance is exceeded, the carcass may not be used for human food. A preslaughter test for penicillin in an easily accessible biological fluid is needed to predict if the concentration of penicillin is below tolerance in the kidney before the bovine is slaughtered. In this study, 12 steers were injected three times with the approved dose (7000 IU) of penicillin at 12-h intervals. Blood and urine samples were collected at intervals after the final dose of penicillin. At each sampling point, one kidney biopsy sample was collected by laparoscopic surgery in the live animal. Another kidney sample was collected at slaughter. Correlations between plasma and kidney concentrations and between urine and kidney concentrations were determined. These correlations predict with 95% confidence that 99% of the animals will have kidney tissue below penicillin tolerance when the plasma concentration of penicillin is below 0.4 ng/mL and/or the urine penicillin concentration is below 140 ng/mL.

Abattoirs↗

Response to criticisms of the US FDA parametric approach for withdrawal time estimation: rebuttal and comparison to the nonparametric method proposed by Concordet and Toutain.

The benefits and drawbacks of using nonparametric methods for estimating product withdrawal times have been debated for many years. This issue was recently revived by Concordet & Toutain (1997a, b) when they described a nonparametric method for withdrawal time estimation. The authors urged the international adoption of this approach, basing their recommendation on three fundamental concerns: (1) the lack of a consistent official procedure for determining a withdrawal time within the European Union (EU); (2) the need to identify a statistical method for improving the international harmonization of withdrawal times for new chemical entities; and (3) a lack of confidence in the robustness of the US Food and Drug Administration/Center for Veterinary Medicine (US FDA) procedure, particularly with respect to minor violations in the underlying parametric assumptions. Due to the critical nature of these issues, the US FDA considers it vital to respond to these concerns. This paper provides a description of the US FDA parametric procedure. We also examine the statistical concerns expressed by Concordet and Toutain, identifying the reasons for our confidence in the US FDA parametric approach. Finally, using their Monte Carlo simulation models, we generate additional datasets to explore the behaviour of their nonparametric procedure and evaluate its ability to support US FDA regulatory activities.

Animal Diseases↗

Dengue surveillance in the Pacific Islands.

Adequate monitoring of dengue activity can be achieved using a combination of mosquito vector surveillance, fever surveillance, sentinel clinicians and laboratory screening. An apparent increase in fever cases or clinically suspected DF should prompt a careful clinical and laboratory investigation. If an outbreak of dengue is confirmed, health authorities will need to implement emergency community-wide control strategies. Laboratories will quickly feel the burden of clinical monitoring of cases admitted with DHF/DSS. Surveillance can change to clinical case definitions as health workers become familiar with the presenting features of DF and DHF/DSS. Criteria for hospital referral and admission must be well understood. Routine laboratory and sentinel surveillance may resume as the epidemic wanes, and should then continue indefinitely to monitor any resurgence of dengue activity.

Dengue↗

Vaccine know-how. Kimberley immunisation study: community nurses immunisation education, knowledge and practice.

In the remote Kimberley Region of Western Australia, community nurses administer almost all childhood vaccines. This paper discusses the immunisation education, knowledge and practice of this group of nurses. This research was part of a larger Kimberley immunisation study. The first phase investigated the immunisation cover and timing of vaccine administration to children in the 0-18 month age group in the Kimberley Region of Western Australia. Phase two investigated immunisation education, knowledge and practice. The study findings suggest that community nurses are knowledgeable about vaccine administration, and administer vaccines appropriately to children with multiple infections, weight loss and failure to thrive. They are also 'active' in following up children due and overdue for vaccines. However, a lack of on-going nursing immunisation education was reported.

Child, Preschool↗

Role of biotin-containing membranes and nuclear distribution in differentiating human endometrial cells.

Human Ishikawa endometrial cells form domes when confluent monolayers are stimulated with fresh fetal bovine serum. Extensive structural and biochemical changes have been detected during the approximately 30 h differentiation period. The earliest detectable change involves the formation of multinucleated structures and the appearance of "granules" that stain for biotin within those structures. Nuclei become associated with each other and are ultimately enclosed within a biotin-containing membrane. Aggregated membrane-sheathed nuclei and the cells containing them begin to elevate from the dish as biotin staining becomes apparent in apical membranes. The elevated structures are called predomes and consist of one or more very large cells containing the sheathed nuclei. Apical membranes of these unusual cells extend far out into the medium in structures that resemble endometrial pinopods. A lumen under the elevated cells fills with transcytosed fluid. As differentiation proceeds, highly concentrated chromatin material that was flattened against apical and lateral membranes of the predome cells begins to disperse. Small mononuclear cells evolve from larger predome cells. Apical membranes of predome and dome cells continue to stain for biotin. Gel electrophoresis of SDS-solubilized biotin-containing membranes, followed by Western blot analysis using avidin-linked peroxidase, resulted in three stained bands with molecular weights similar to those of the mitochondrial carboxylases: propionyl carboxylase, methylmalonyl carboxylase, and pyruvate carboxylase.

Biotin↗

Measuring the impact of conjugate vaccines on invasive Haemophilus influenzae type b infection in Western Australia.

Haemophilus influenzae type b (Hib) causes serious infections in 26-59 per 100,000 non-Aboriginal Australian children under five years of age. Aboriginal children suffer much higher rates of infection (> or = 150 per 100,000), and at an earlier age, and have a greater risk of death and disability due to Hib infection. In 1992 and 1993, four conjugate Hib vaccines were introduced in Australia, and a nationally funded program of infant vaccination was begun in July 1993. This study aimed at evaluating the effectiveness of Hib vaccination in Aboriginal and non-Aboriginal children in Western Australia using a population-based active surveillance system for non-Aboriginal children and a case control study for Aboriginal children. The incidence of invasive Hib disease in non-Aboriginal children fell from 30.9 per 100,000 before vaccination was available to 6.3 per 100,000 in the second year after its introduction. The vaccine efficacy was estimated to be 80 per cent for Aboriginal children (odds ratio 0.20, 95 per cent CI 0.01-2.76) and, after adjustment for confounders, 75 per cent (odds ratio 0.25, CI 0.02-3.66). Based on the adjusted value (75 per cent), and using a Bayesian approach, we estimate that the posterior probability was 0.55 that the true vaccine efficacy is greater than 70 per cent, and 0.69 that the efficacy is greater than 50 per cent. We conclude that Hib vaccination is effective in preventing invasive Hib disease in Aboriginal and non-Aboriginal children in Australia.

Bacteremia↗

Induction of heat labile alkaline phosphatase by butyrate in differentiating endometrial cells.

The addition of 2 mM sodium butyrate to monolayers enhances differentiation of Ishikawa endometrial cells. Cells from this cell line have been shown to enlarge and lift off the dish into dome structures over a period of 24-48 h in response to a factor in fetal bovine serum (FBS) [Fleming, 1995 J Cell Biochem in press]. When butyrate is added to monolayers, together with FBS, three- to fourfold higher numbers of differentiated structures, domes and predomes, can be counted. It had previously been shown [Holinka et al., 1986b] that estradiol induces heat stable placental alkaline phosphatase in Ishikawa cells. The addition of butyrate, on the other hand, results in a significant increase in levels of a heat labile alkaline phosphatase isozyme. The heat labile isozyme is also increased to some extent in cells stimulated to differentiate in response to FBS in the absence of butyrate. Differential inhibition by homoarginine and phenylalanine indicates that butyrate is inducing the liver-bone kidney isozyme that is found in endometrial glands in vivo.

Alkaline Phosphatase↗

Reward shifts and motor responses following microinjections of opiate-specific agonists into either the core or shell of the nucleus accumbens.

Differences in pharmacology, anatomical connections, and receptor densities between the "core" and "shell" of the nucleus accumbens suggest that behavioral activity normally modulated by the accumbens, such as reward and motor functions, may be differentially regulated across the mediolateral axis. This study investigated the effects of opiate receptor-specific agonists on reward and motor functions in either the accumbens core or shell, using the intracranial self-stimulation (ICSS) rate-frequency curve-shift method. Microinjections of the mu opiate receptor-specific agonist, DAMGO (vehicle, 0.03 nmol, and 0.3 nmol), or the delta opiate receptor-specific agonist DPDPE (vehicle, 0.3 nmol, 3.0 nmol), were administered bilaterally in a random dose order with a minimum of 3 days between injections. Rats were tested over three consecutive 20-min rate-frequency curves immediately following a microinjection to investigate the time course of drug effects. Both opiate agonists decreased the ICSS frequency necessary to maintain half-maximal response rates when injected into the medial and ventral shell region of the accumbens. However, DAMGO microinjections into the lateral accumbens core or the control site of the caudate increased the frequency necessary to elicit half-maximal response rates, while DPDPE microinjections into these regions had no effect. Evaluation of motor effects show that administration of DAMGO resulted in a suppression of activity in all locations. In contrast, DPDPE microinjections resulted in little or no effect on lever pressing activity at any location.

Analgesics↗

Sequelae of Haemophilus influenzae type b meningitis in aboriginal and non-aboriginal children under 5 years of age.

Between 1984 and 1990, 257 cases of Haemophilus influenzae type b (Hib) meningitis occurred in children under five years of age in Western Australia. We obtained information on possible sequelae in 131 cases (all non-Aboriginal) by medical record review and parental interview, and in a further 116 cases (60 non-Aboriginal, 56 Aboriginal) by medical record review only; no follow-up information was available for ten children (nine non-Aboriginal, 1 Aboriginal). The incidence of Hib meningitis in children under five years of age was 26.3 per 100,000 for non-Aboriginal and 152.2 per 100,000 for Aboriginal children. The case fatality rate was 3.5% for non-Aboriginal children and 14.0% for Aboriginal children. Sequelae were recorded for 17.1% of non-Aboriginal and 22.4% of Aboriginal children who survived Hib meningitis. Surviving Aboriginal children experienced severe sequelae following Hib meningitis almost three times more frequently than surviving non-Aboriginal children (10.5% vs 3.6%), although mild and moderate sequelae were not more common in Aboriginal children. The information on incidence and severity of sequelae in this study was obtained by chart review and parental interview, and hence may be subject to error or bias, particularly for mild and moderate disabilities. Outcomes like death and severe sequelae, such as cerebral palsy and profound intellectual and physical disability, are less subject to bias. Of Aboriginal children who contracted Hib meningitis in Western Australia over the study period, 22.8% either died or had severe sequelae, while only 7.0% of non-Aboriginal children experienced these severe outcomes.

Cerebral Palsy↗

Cytoplasmic and periplasmic expression of a highly basic protein, human interleukin 4, in Escherichia coli.

Human IL-4 (hIL-4) has been cloned from a human T cell line based on its homology to the murine IL-4 cDNA sequence. We have compared cytoplasmic and extra-cytoplasmic expression of this basic protein in Escherichia coli using various combinations of promoters, replicons and host strains. Strains producing a cytoplasmic product were most successful at heterologous protein expression, producing up to 500 mg/l of an inactive aggregated form of the protein. The biological activity of the protein could be restored by refolding the protein with guanidine hydrochloride and glutathione giving a specific activity identical to that of IL-4 derived from CHO cell lines stably transformed with an hIL-4 expression plasmid. Strains designed to secrete human IL-4 into the periplasmic space produced far less protein (approximately 5 mg/l). However, a significant fraction of this protein was detected in the culture medium. This fraction appeared to be soluble after ultracentrifugation, and demonstrated high specific activity without refolding. Leakage of heterologous protein into the culture medium may be a viable way to recover biologically active products without relying on the denaturation and refolding in vitro that can, at times, yield incorrectly folded gene product.

Amino Acid Sequence↗

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. III. Rhythms in physiological functions.

Oral and rectal temperature, urinary excretion of adrenaline and noradrenaline, and heart rate were measured in 28 watchkeepers working a "4-on/8-off" routine, and in 25 dayworkers, on board ships. Readings of oral temperature were taken over 4-hourly periods of up to two weeks; the rectal temperature, urine, and heart rate data were collected on selected days within these periods. Analysis of watchkeepers' temperatures and unconjugated catecholamine excretions showed slight signs of an interactive adaptation to time of day and hours of work, but it was clear that full phase adjustment of the circadian rhythms to shifted hours of work did not occur. The "split" pattern of sleep imposed by the watch system may be a major factor in preventing complete adaptation of physiological rhythms to shift work in the shipboard situation; this problem could be overcome by devising a system that allows sleep to be taken in a single uninterrupted block each day.

Body Temperature↗

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. IV. Rhythms in performance and alertness.

Performance scores on both a simple detection task and a complex visual judgment task, together with subjective alertness ratings, were collected 4-hourly from 19 watchkeepers working a "4-on/8-off" routine, and from 20 dayworkers, over consecutive days of voyages on merchant ships. Adaptation of the circadian rhythms in the measures to the shifted hours of work of the three sections of the watchkeeping crews was at best only partial. These rhythms resulted in a depression of the levels of most measures during the night hours, which was exacerbated by the effects of recent awakening from sleep. It is suggested that these unwanted variations in operational effectiveness could be largely removed by replacing the 4-on/8-off watchkeeping system, with its associated "split" sleep pattern, by one which allows a single full length sleep each day. Such a system would encourage better adaptation of the rhythms; effects of recent awakening could be avoided by the provision of an adequate "waking up" period before duty begins.

Arousal↗

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. V. Effects of time zone crossings.

Daily diary records of sleep and activity, and 4-h measurements of body temperature, performance and subjective alertness were collected on board ship from 15 watchkeepers on the 4-on/8-off system, and from 28 dayworkers, on both westward and eastward transatlantic voyages. The data from a balanced sample of the subjects were analysed over selected 8-d periods of the voyages where four or five time zones were crossed. During these periods the average amount of daily sleep obtained by dayworkers on the eastward voyage was more than 1 h less than that on the westward voyage, and its quality was rated lower. Watchkeepers' main sleep was also shorter when travelling eastward, but this reduction was partially compensated for by a slightly longer secondary sleep. With the exception of subjective alertness on the eastward voyage, the basic phase of the circadian rhythms in the measured variables adjusted appropriately to the clock changes associated with the time zone crossings. The normal shape of the average daily curves was, however, altered differentially in the two directions of travel; as a result, morning levels of all variables were lower on the eastward voyage than on the westward, but evening levels were higher. These distortions of rhythm waveforms, which probably arose from a combination of endogenous and exogenous factors, add another dimension to the basic problem caused by the effects of circadian rhythms on operational efficiency in the shipboard situation. This problem can only be solved by the development of alternative watchkeeping systems which take full account of these rhythms.

Attention↗