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Biomedical subjects

D Anderson

Publications and source records attributed to D Anderson.

At least 19 recordsLinked to original sources

Relationship between plasma selenium concentrations and lower genital tract levels of HIV-1 RNA and interleukin type 1beta.

OBJECTIVE: To examine the relationship between selenium nutritional status and intermediates of human immunodeficiency virus (HIV)-1 transmission. DESIGN: Prospective cohort study. SETTING: A study clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania. SUBJECTS: A total of 340 HIV-1-infected pregnant women with gestational ages 12-27 weeks. METHODS: Women's plasma selenium concentrations were determined at enrollment and modeled as tertiles (tertile 1: <114 microg/l (reference); tertile 2: 114-131 microg/l; tertile 3: >131 microg/l). Cervicovaginal lavage specimens were obtained at 36 weeks of gestation to determine HIV-1 RNA and interleukin-1beta (IL-1beta) levels. In subgroup analyses, 123 women with genital tract infections at enrollment were excluded. RESULTS: Plasma selenium concentrations >or=114 microg/l were related to increased risk of lower-genital shedding of HIV-1 RNA. Excluding women with genital tract infections strengthened the associations (relative risk (RR) tertile 2: 1.46, 95% confidence interval (CI)=1.10, 1.92; RR tertile 3: 1.39, 95% CI=1.05, 1.84). There was evidence for an association between plasma selenium concentrations >or=114 microg/l and increased HIV-1 RNA levels among the entire cohort and after excluding women with genital tract infections. There was no association between plasma selenium and IL-1beta concentrations. CONCLUSIONS: High selenium status may lead to increased risk of genital HIV-1 shedding, but data from other studies indicate that the evidence is mixed. Results from ongoing selenium trials are awaited to clarify the impact of selenium on HIV-1-related transmission endpoints. SPONSORSHIP: National Institute of Child Health and Human Development (NICHD R01 32257) and the Fogarty International Center (NIH D43 TW00004).

Adult↗

The effects of male age on sperm DNA damage in healthy non-smokers.

BACKGROUND: The trend for men to have children at older age raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. METHODS: We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (mean age: 46.4 years, range: 22-80 years) with no known fertility problems using the sperm Comet analyses. RESULTS: The average percentage of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, P = 0.006), but there was no age association for damage measured under neutral conditions (P = 0.7). Men who consumed >3 cups coffee per day had approximately 20% higher percentage tail DNA under neutral but not alkaline conditions compared with men who consumed no caffeine (P = 0.005). CONCLUSIONS: Our findings indicate that (i) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks and (ii) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization, increasing the risks of developmental defects and genetic diseases among offspring.

Adult↗

A first look at duloxetine (Cymbalta) in a postmortem laboratory.

Duloxetine (Cymbalta) is manufactured by Eli Lilly and Company and is the newest antidepressant to be approved by the Food and Drug Administration (FDA). Duloxetine is a potent serotonin and norepinephrine reuptake inhibitor that is also used for the management of pain associated with diabetic peripheral neuropathy. With the introduction of any new drug, toxicology laboratories around the nation experience the same problems: lack of information about the chemical and physical properties of the new drug, detection methodologies from biological specimens, and interpretation of quantitative values. Since its FDA approval in 2002, the Los Angeles County Department of Coroner Toxicology Laboratory has detected and quantitated duloxetine in 12 postmortem cases. The isolation of duloxetine from postmortem specimens consisted of a basic, liquid-liquid (n-butylchloride) extraction procedure. Duloxetine was detected in our general, pharmaceutical, basic drugs screen that utilizes gas chromatography-nitrogen-phosphorus detection (GC-NPD) and GC-mass spectrometry (MS), and the quantitation was specifically by GC-MS. Linearity was achieved from 0.05 to 3.0 mg/L with the limit of detection at 0.03 mg/L. Presented are the case histories, demographics, cause/manner of death, and the postmortem tissue distribution ranges of duloxetine: central blood, not detected (ND)-0.59 mg/L (12 cases); femoral blood, ND-0.26 mg/L (9 cases); vitreous humor, ND-0.23 mg/L (4 cases); liver, 0.28-22 mg/kg (8 cases); gastric contents, 0.08-86 mg total (6 cases); bile, 0.57-3.1 mg/L (7 cases); and urine, 0.07-0.47 mg/L (6 cases). The detection and quantitation of duloxetine in these 12 case studies are considered the first to be reported in the literature; all are designed to aid the forensic toxicologist with the interpretation of his/her own casework.

Adult↗

Patients with acute myocardial infarction have an inaccurate understanding of their risk of a future cardiac event.

BACKGROUND: Accurate perceptions of future cardiac risk are important to ensure informed treatment choices and lifestyle adaptation in patients following myocardial infarction (MI). The aim of this study was to investigate whether risk perceptions of patients with MI were accurate compared with an established clinical risk model. METHODS: Seventy-nine consecutive patients with acute MI admitted to the Coronary Care Unit, Auckland Hospital, completed a questionnaire assessing risk perceptions. Clinical data were used to calculate patients' Thrombolysis In Myocardial Infarction (TIMI) risk scores, a validated predictive model of prognosis. The main outcome measures were the associations between perceived risk, TIMI risk scores and troponin T. RESULTS: Patients' risk perceptions showed no correlation with thrombolysis in myocardial infarction risk scores (r = -0.06; P = 0.61) or with troponin T (r = -0.07; P = 0.53). Patients' risk perceptions were not significantly associated with age or sex, and were not significantly higher in those who had experienced a previous MI, a family history of coronary heart disease, diabetes or smokers. Higher perceived risk was significantly associated with a number of illness perceptions, including worse consequences of the MI and lower beliefs in the benefit of treatment. Patients who overestimated their risk were more anxious than other patients (F(2, 73) = 22.97; P = 0.0001). CONCLUSION: Patients with MI ideas about their personal risk of future MI are not congruent with their clinical risk assessments. Inpatient hospital care appears to be unsuccessful in communicating prognosis effectively to patients. Improving the accuracy of risk perceptions may help decrease unnecessary cardiac anxiety and invalidism in some patients and prompt risk-reducing behaviours in others.

Aged↗

Charge pumping in carbon nanotubes.

We demonstrate charge pumping in semiconducting carbon nanotubes by a traveling potential wave. From the observation of pumping in the nanotube insulating state we deduce that transport occurs by packets of charge being carried along by the wave. By tuning the potential of a side gate, transport of either electron or hole packets can be realized. Prospects for the realization of nanotube based single-electron pumps are discussed.

Journal Article↗

Associations between the use of complementary and alternative medications and demographic, health and lifestyle factors in mid-life Australian women.

OBJECTIVE: To determine the prevalence and types of complementary and alternative medications (CAMs) used by menopausal women living in South-East Queensland, Australia; and profile the women who are using CAMs through sociodemographic characteristics, self-rated health status, lifestyle and preventative health strategies. METHOD: This study was a secondary data analysis of data collected by postal questionnaire from 886 women aged 48-67 years participating in the Queensland Midlife Women's Health Study. The outcome measure was CAM use, distinguished by three categories: herbal therapies, phytoestrogens and nutritional intake (supplements and healthy eating). RESULTS: The overall prevalence of CAM use among mid-life Australian women was 82% which included therapeutic techniques (83%), nutritional supplements (66.8%), phytoestrogens (55.8%), herbal therapies (41.3%), Evening Primrose oil (34%) and vitamin E (28.8%). CAM users, when compared to non-users, were more likely to be previous (p < 0.05) but not current users (p < 0.05) of hormone therapy (HT), higher educated (p < 0.05), low to middle income earners (p < 0.001) and have participated in self-breast examination (p < 0.01). They were also more likely to report good general health (p < 0.05) and improved physical functioning without limitations due to health (p < 0.05). CAM users were less likely to be aged over 55 years (p < 0.05) and smoke more than 20 cigarettes per day (p < 0.001). CONCLUSIONS/IMPLICATIONS FOR HEALTH RESEARCH: As prevalence of current CAM use in this population group is considerably higher than HT use, health education programs to assist mid-life women to understand the scientific evidence (or lack of it) for their efficacy is recommended.

Age Distribution↗

Intramembranous absorption rate is unaffected by changes in amniotic fluid composition.

Experiments were performed to determine the effect of amniotic fluid dilution on the rate of intramembranous absorption. Seven fetal sheep at 118 days gestation were instrumented with a shunt between the trachea and esophagus and arterial and venous vascular catheters. In addition, the urachus of the fetal bladder was ligated, and a catheter was placed in the bladder. Ligation of the urachus does not interfere with urine flow into the amnion. After 5 days of recovery, fetuses were randomly assigned to one of two protocols; all fetuses completed both protocols. In the fetuses in the control period, continuous urine flow measurement was begun. In the fetuses assigned to the isovolumic dilution protocol, continuous urine flow measurement was also begun and, in addition, amniotic fluid was continually exchanged with lactated Ringer solution on an isovolumic basis. After 3-4 days, fetal blood pressures and amniotic fluid volumes were determined. Amniotic fluid volumes were determined by drainage. Each fetus was then assigned to the remaining protocol. The presence of the tracheal-esophageal shunt and the ligation of the urachus allowed the rate of intramembranous absorption to be calculated. Isovolumic exchange showed no effect on fetal vascular pressures, blood-gas values, or urine production. We could demonstrate no effect of isovolumic dilution of amniotic fluid on its volume. However, we were able to demonstrate an inverse relationship between amniotic fluid volume and intramembranous absorption (P < 0.02).

Absorption↗

Regulatory response to washout of amniotic fluid in sheep.

To test the hypothesis that a substance present in the amniotic fluid could serve as a regulator of amniotic fluid volume, we drained and discarded amniotic fluid while replacing it with lactated Ringer solution that was isotonic to amniotic fluid. Seven ewes with singleton fetuses at 119 +/- 1 days of gestation (mean +/- SE) were instrumented with multiple indwelling catheters in the pedal artery, pedal vein, and amniotic cavity. During the exchange periods, an average of 3,019 +/- 171 ml/day of lactated Ringer solution was infused into the amniotic cavity while an equal amount of amniotic fluid was pumped out and discarded. During the control period, amniotic fluid composition and volume were not altered. Exchange and control periods started with the same amniotic fluid volume, lasted 3 or 4 days, and were randomized with regard to order. Amniotic fluid volume measured by vacuum drainage was 556 +/- 98 ml at the end of the control period and 986 +/- 209 ml (P = 0.03) at the end of the exchange period. Fetal arterial blood gases, hemodynamic parameters and the osmolality gradient between fetal plasma and amniotic fluid were not altered by the exchange process. A linear relationship between the control amniotic fluid volume and the volume at the end of the exchange period (P = 0.003) suggests that the animals with larger control volumes responded to isovolumic dilution with a larger volume increase. We conclude that amniotic fluid may contain a substance that regulates amniotic volume.

Absorption↗

Transverse modulational instability of partially incoherent soliton stripes.

Based on the Wigner distribution approach, an analysis of the effect of partial incoherence on the transverse instability of soliton structures in nonlinear Kerr media is presented. It is explicitly shown that for a Lorentzian incoherence spectrum the partial incoherence gives rise to a damping which counteracts, and tends to suppress, the transverse instability growth. However, the general picture is more complicated and it is shown that the effect of the partial incoherence depends crucially on the form of the incoherence spectrum. In fact, for spectra with finite rms-width, the partial incoherence may even increase both the growth rate and the range of unstable, transverse wave numbers.

Journal Article↗

Current dynamics during disruptions in large tokamaks.

Self-consistent modeling of the evolution of the plasma current during disruptions in large tokamaks is presented, taking into account both the generation of runaway electrons and their backreaction on the electric field. It is found that the current profile changes dramatically, so that the postdisruption current carried by runaway electrons is much more peaked than the thermal predisruption current. Although only a fraction of the thermal current is converted into runaway electrons, the central current density increases significantly for typical parameters in JET and ITER. It is also shown that the radial runaway profile can easily become filamented in the radial direction.

Journal Article↗

Melanin protects melanocytes and keratinocytes against H2O2-induced DNA strand breaks through its ability to bind Ca2+.

Reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O(2)) are produced in the skin under the influence of UV radiation. These compounds are highly reactive and can induce DNA lesions in epidermal cells. Melanin is considered to protect human skin against DNA damage by absorbing UV radiation. We have investigated whether melanin can, in addition, offer protection against the effects of H(2)O(2) in human melanocytes and HaCaT keratinocytes. In the present study, it was shown that 40 and 100 microM H(2)O(2) increased the number of DNA strand breaks as measured using the comet assay, in melanocytes of Caucasian origin. In melanocytes of the same origin in which melanin levels were increased by culturing in presence of 10 mM NH(4)Cl and elevated l-tyrosine, H(2)O(2)-induced DNA damage was reduced compared to that in control melanocytes. Similarly, HaCaT cells that were loaded with melanin were better protected against H(2)O(2)-induced DNA strand breaks than control HaCaT cells. These protective effects of melanin were mimicked by the intracellular Ca(2+)-chelator BAPTA. Thus, BAPTA reduced the level of H(2)O(2)-induced DNA strand breaks in melanocytes. Like BAPTA, melanin is known to be a potent chelator of Ca(2+) and this was confirmed in the present study. It was shown that melanin levels in melanocytic cells correlated directly with intracellular Ca(2+) binding capacity and, in addition, correlated inversely with H(2)O(2)-induced increases in intracellular Ca(2+). Our results show that melanin may have an important role in regulating intracellular Ca(2+) homeostasis and it is suggested that melanin protects against H(2)O(2)-induced DNA strand breaks in both melanocytes and keratinocytes and through its ability to bind Ca(2+).

Calcium↗

Stable, stoichiometric delivery of diverse protein functions.

As contemporary "genomics" steadily reveals an increasing number of novel gene sequences, the need for efficient methodologies to functionally characterize these genes in vivo increases significantly. Reliable coupling of target gene expression to a variety of surrogate reporter functions is critical to properly assay novel gene function in complex cell populations. Ideally, independent target and reporter proteins would be derived from a single open reading frame creating a stoichiometric relationship without obscuring subcellular localization. We report here effective strategies for assaying gene function through the stable production of chimeric polyproteins, processed intracellularly by inclusion of an intervening 19-amino-acid sequence from the 2A region of the Foot and Mouth Disease virus. Using drug-resistance and flow cytometry-based assay systems, we demonstrate that diverse protein functions are effectively delivered to various cell types by retroviral constructs as single 2A-cleaved polyproteins. For example, cells infected with a retrovirus encoding a nuclear cell cycle regulator, linked via the 2A-motif to a marker membrane protein, showed a direct correlation between cell cycle arrest and surface marker level. This demonstrates the utility of this methodology for stable and stoichiometric delivery of distinctly localized protein functionalities. In particular, the ability to exploit multiple cellular functions will serve to accelerate the functional characterization of gene products and facilitate novel gene therapy approaches.

Amino Acid Motifs↗

Features of modulational instability of partially coherent light: importance of the incoherence spectrum.

It is shown that the properties of the modulational instability of partially coherent waves propagating in a nonlinear Kerr medium depend crucially on the profile of the incoherent field spectrum. Under certain conditions, the incoherence may even enhance, rather than suppress, the instability. In particular, it is found that the range of modulationally unstable wave numbers does not necessarily decrease monotonically with increasing degree of incoherence and that the modulational instability may still exist even when long wavelength perturbations are stable.

Journal Article↗

Midterm results of the Ross procedure.

OBJECTIVE: The lack of durable bioprosthetic valves and the inherent risks associated with anticoagulation for mechanical valves have led to the continued use of the Ross procedure, particularly in the pediatric population. METHODS: We have reviewed our mid-term results retrospectively, following the Ross operation in both pediatric and adult groups. RESULTS: Over a 11-year period from August 1991 to August 2002, 60 patients underwent the Ross procedure. The median age was 15 years (6-804 months), of which 63% were males and 55% were under the age of 20 years. The main indications were: aortic stenosis in 47 patients; aortic insufficiency in 6 patients; and mixed aortic valve disease in 28 patients. Fifteen patients had previously undergone balloon dilatation of the aortic valve, 4 had open valvotomy and 3 had both valvuloplasty procedures. The pulmonary autograft was implanted as a sub-coronary implant until 1995 (30%) after which time it was implanted using a partial inclusion cylinder technique (70%). There have been no deaths reported in this series. Over a median follow-up period of 59 months (2-122 months), there have been four re-operations for repair of autograft leak, and 2 adult patients have had autograft replacements. CONCLUSIONS: Despite the increased technical complexity, the Ross procedure can be performed safely in both paediatric and adult populations with satisfactory medium term results.

Adolescent↗

Preliminary study of shunt related death in paediatric patients.

Hydrocephalus is a condition commonly encountered in paediatric and adult neurosurgery and cerebrospinal fluid (CSF) shunting remains the treatment of choice for many cases. Despite improvements in shunt technology and technique, morbidity and mortality remain. The incidence of early shunt obstruction is high with later failures seen less frequently. This review aims to examine mortality associated with mechanical failure of CSF shunts within Queensland. Neurosurgical and Intensive Care databases were reviewed for cases of mortality associated with shunt failure. Eight cases were identified between the years of 1992 and 2002 with the average age at death 7.7 years. Deaths occurred on average 2 years after last shunt revision. Seven of the eight patients lived outside the metropolitan area. Shunting remains an imperfect means of treating hydrocephalus. Mortality may be encountered at any time post surgery and delays to surgical intervention influence this. Alternative measures such as third ventriculostomy or the placement of a separate access device should be considered. In the event of emergency, a spinal needle could be used to access the ventricle along the course of the ventricular catheter.

Cerebrospinal Fluid Shunts↗

Menopause in Australia and Japan: effects of country of residence on menopausal status and menopausal symptoms.

OBJECTIVES: The aim of the study was to explore the effects of country of residence on menopausal status and menopausal symptoms in Australian and Japanese women. The study objectives included exploring the impact of country of residence (Australia and Japan) and menopausal status on menopausal symptoms, and identifying whether country of residence (Australia and Japan) moderates the relationship between menopausal status and menopausal symptoms. METHODS: Analyses are based on 1743 women aged between 40 and 60 years who participated in the multi-race, multi-site, cross-sectional study of mid-aged women called the Australian and Japanese Midlife Women's Health Study (AJMWHS) in 2001--2002. Study participants completed a mailed questionnaire that contained questions on a variety of health-related topics. RESULTS: In both cultures there was a similar increase in prevalence of depression (p < 0.001), somatic symptoms (p < 0.001) and vasomotor symptoms (p < 0.001) at perimenopause. Australian women experienced more night sweats than Japanese women but the prevalence of hot flashes was not statistically different. Postmenopausal Japanese women had more somatic, psychological and sexual symptoms. The main effect for menopausal status and the interaction effect of country of residence was significant in the somatic symptoms (p < 0.001), but not in any of the other areas. CONCLUSIONS: Vasomotor, psychological and somatic symptoms decrease after menopause in Australian women, with only sexual symptoms continuing. In Japanese women, somatic, psychological and sexual symptoms remain high after menopause. It is possible that westernization may be having a significant impact on the aging of women in Japan and it is, therefore important to capture through research just what this impact may be.

Adult↗

Parallel evaluation of doxorubicin-induced genetic damage in human lymphocytes and sperm using the comet assay and spectral karyotyping.

In recent years, two techniques for detecting genetic damage in the whole genome have gained importance: the alkaline comet assay, to detect DNA damage such as strand breaks and alkali-labile sites, and a multicolour FISH method, spectral karyotyping (SKY), to identify chromosomal aberrations simultaneously in all metaphase chromosomes. In the present study, the induction of DNA damage in human sperm and lymphocytes in vitro has been studied employing an anticancer drug, doxorubicin (DX). An increase in DNA damage was observed with the comet assay as the median per cent head DNA of sperm significantly decreased from 82.07 and 85.14% in the untreated control groups to 63.48 and 72.52% at doses of 0.8 micro M DX. At 1.6 micro M the percentage declined to 60.96% (the corresponding tail moment increased from 4.42 to 12.19). In stimulated lymphocytes, a significant increase was observed in tail moment, from 0.72 and 0.53 in controls to 15.17 and 12.10 at 0.2 micro M DX, continuing at the same level to a final concentration of 1.6 micro M. Structural aberrations found in the parallel SKY study in stimulated lymphocytes at 0.2 micro M DX consisted of 14% chromatid-type and 2% chromosome-type aberrations; none were found in controls. The SKY results correlate very well with the findings of the comet assay in lymphocytes where DNA damage was observed at similar doses. This study is the first reporting use of the comet assay and SKY analysis in parallel after chemical treatment. The potential of the two techniques together is evident, as they represent a set of assays feasible for evaluating damage in human somatic and germ cells after chemical treatment (i) by direct observation of two different end-points, detecting general DNA damage and chromosomal aberrations and (ii) by extrapolation from lymphocytes to sperm, which provides a 'parallelogram' approach in human cells.

Adult↗