Adverse events in British hospitals. Preventive strategies, not epidemiological studies, are needed.
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Australia↗
Biomedical subjects
T V Nguyen
Publications and source records attributed to T V Nguyen.
Stage-dependent localization of a novel gene product of the malaria parasite, Plasmodium falciparum.
A novel Plasmodium falciparum gene, MB2, was identified by screening a sporozoite cDNA library with the serum of a human volunteer protected experimentally by the bites of P. falciparum-infected and irradiated mosquitoes. The single-exon, single-copy MB2 gene is predicted to encode a protein with an M(r) of 187,000. The MB2 protein has an amino-terminal basic domain, a central acidic domain, and a carboxyl-terminal domain with similarity to the GTP-binding domain of the prokaryotic translation initiation factor 2. MB2 is expressed in sporozoites, the liver, and blood-stage parasites and gametocytes. The MB2 protein is distributed as a approximately 120-kDa moiety on the surface of sporozoites and is imported into the nucleus of blood-stage parasites as a approximately 66-kDa species. Proteolytic processing is favored as the mechanism regulating the distinct subcellular localization of the MB2 protein. This differential localization provides multiple opportunities to exploit the MB2 gene product as a vaccine or therapeutic target.
Amino Acid Sequence↗
Clinical role of quantitative ultrasound in the assessment of osteoporosis in individual patients.
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Humans↗
Risk factors for proximal humerus, forearm, and wrist fractures in elderly men and women: the Dubbo Osteoporosis Epidemiology Study.
Fractures of the proximal humerus, forearm, and wrist account for approximately one third of total osteoporotic fractures in the elderly. Several risk factors for these fractures were evaluated in this prospective study of 739 men and 1,105 women aged > or =60 years in Dubbo, Australia. During follow-up (1989-1996), the respective incidences of humerus and of forearm and wrist fractures, per 10,000 person-years, were 22.6 and 33.8 for men and 54.8 and 124.6 for women. Independent predictors of humerus fracture were femoral neck bone mineral density (FNBMD) (relative risk (RR) = 2.3, 95% confidence interval (CI): 1.2, 4.5) in men and FNBMD (RR = 2.4, 95% CI: 1.7, 3.5) and height loss (RR = 1.1, 95% CI: 1.0, 1.2) in women. For forearm and wrist fractures, risk factors were FNBMD (men: RR = 1.5, 95% CI: 1.0, 2.3; women: RR = 1.5, 95% CI: 1.2, 1.9) and height loss (men: RR = 1.2, 95% CI: 1.0, 1.3; women: RR = 1.1, 95% CI: 1.0, 1.2). In addition, dietary calcium (men: RR = 2.0, 95% CI: 1.0, 3.6) and a history of falls (women: RR = 1.9, 95% CI: 1.4, 2.6) were also significant. These data suggest that elderly men and women largely share common risk factors for upper limb fractures and that FNBMD is the primary risk factor.
Accidental Falls↗
Improved mapping of pharmacologically induced neuronal activation using the IRON technique with superparamagnetic blood pool agents.
The use of functional magnetic resonance imaging (fMRI) techniques for evaluation of pharmacologic stimuli has great potential for understanding neurotransmitter dynamics for a number of brain disorders, such as drug abuse, schizophrenia, epilepsy, or neurodegeneration. Unfortunately, blood oxygenation level-dependent (BOLD) imaging at common fields strengths, such as 1.5 or 3 T, has very low sensitivity and contrast-to-noise ratios (CNRs). We demonstrate here the utility of using an intravascular superparamagnetic iron oxide contrast agent with a long plasma half-life for evaluation of hemodynamic changes related to dopaminergic stimuli using amphetamine or the cocaine analog 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT). We refer to this technique as increased relaxation with iron oxide nanoparticles (IRON). Results obtained here show that even at field strengths as high as 4.7 T, one can obtain increases in CNR by factors of 2-3 over BOLD imaging that lead to greater than an order of magnitude increase in statistical power with greatly increased sensitivity to hemodynamic changes in brain regions difficult to observe using BOLD imaging. Furthermore, use of the intravascular contrast agent allows for a meaningful physiologic parameter to be measured (relative cerebral blood volume (rCBV)), compared to conventional BOLD imaging.
Animals↗
Immunocytochemical characterization of viruses and antigenic macromolecules in viral vaccines.
Gold immunolabeling combined with negative staining (GINS) provides a valuable immunocytochemical approach that allows a direct ultrastructural definition of all viral vaccine constituents that share common antigenic features with pathogenic viral particles. These results have implications for the development of viral vaccines since it has been demonstrated that incomplete viral particles such as natural empty capsides and Rotavirus-like particles lacking the infective genome are potential candidates for the production of neutralizing antibodies. Furthermore comparative results of the application of GINS to either inactivated vaccines or unfixed samples provide direct evidence that even after inactivation specific antigenic sites are still available for gold immunolabeling.
Animals↗
Bone mineral density in prepubertal asthmatics receiving corticosteroid treatment.
OBJECTIVE: To examine whether bone mass is reduced in prepubertal, asthmatics receiving high doses of inhaled corticosteroids. METHODOLOGY: A cross-sectional comparison of lumbar spine-bone mineral density (LS-BMD) was undertaken in 76 subjects after stratifying them according to dosage and administration route of corticosteroid. RESULTS: Weight was the only independent predictor of LS-BMD (r(2) = 0.38). Children receiving greater than 800 microg/day of inhaled corticosteroid plus intermittent oral corticosteroid had a significantly lower weight-adjusted LS-BMD than children treated with 400-800 microg/day of inhaled corticosteroid (mean difference: 0.06 g/cm(2), 95% confidence interval (CI): - 0.02 to - 0.10). A significant difference in weight-adjusted LS-BMD persisted when all children receiving greater than 800 microg/day of inhaled corticosteroid, irrespective of additional oral corticosteroid treatment, were compared with children receiving 400-800 microg/day of inhaled corticosteroid (mean difference: - 0.05 g/cm(2), 95%CI interval: -0.02 to - 0.09). Bone mass was similar in children not receiving any inhaled corticosteroid and those treated with 400-800 microg/day of inhaled corticosteroid. CONCLUSIONS: A reduced bone mass in prepubertal asthmatic children receiving high doses of inhaled corticosteroids may predetermine a compromised peak bone mass and increase osteoporotic fracture risk in adulthood.
Absorptiometry, Photon↗
ApaI polymorphisms of the vitamin D receptor predict bone density of the lumbar spine and not racial difference in bone density in young men.
A number of previous investigations showed significant associations between polymorphisms of the vitamin D receptor (VDR) gene and bone mineral density (BMD). BMD is influenced by hormones and the rate of skeletal remodeling. A study was performed to investigate the possible relationship between Apa I, Bsm I, Taq I, and Fok I polymorphisms of the VDR gene and serum 1,25-dihydroxyvitamin D (1,25[OH]2D), osteocalcin, and propeptide of type I collagen (PICP)-markers of bone turnover, total body calcium, and BMD of the total body, radius, lumbar spine, trochanter, and femoral neck-in 39 young adult black men of 20 to 40 years of age and 44 age-, height-, and weight-matched white men. The distribution of each of the four alleles of the VDR genotypes was similar in the two racial groups. The Apa I VDR genotype was associated with serum PICP (P =.0494) but not with serum 1,25(OH)2D or serum osteocalcin. A significant association between the Apa I VDR genotype and BMD of the lumbar spine (P =.0291) was also observed. However, the Bsm I, Taq I, and Fok I genotypes were not significantly associated with BMD or serum osteocalcin, PICP, or 1,25(OH)2D. Multivariate stepwise analysis indicated that (1) the Apa I VDR genotype was associated with BMD of the lumbar spine in the two groups together; with total body calcium and BMD of the total body, radius, trochanter, and femoral neck in the black men; and with BMD of the radius in the white men; analysis also indicated that (2) race was significantly associated with total body calcium and BMD of the total body, lumbar spine, and femoral neck. In summary, the Apa I VDR genotype is associated with serum PICP and BMD at a number of sites but does not contribute to or account for racial differences in BMD in young adult men.
Adult↗
On the analysis and interpretation of spontaneous variability of cardiac output.
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Cardiac Output↗
Blood pressure is linked to salt intake and modulated by the angiotensinogen gene in normotensive and hypertensive elderly subjects.
OBJECTIVES: To evaluate salt sensitivity in elderly subjects with different forms of hypertension and controls and to investigate any modulation by genotype DESIGN: Randomized, double-blinded, placebo-controlled latin-square SETTING: Tertiary referral hospital PARTICIPANTS: Community subjects (n = 46) aged > or = 60 years classified as isolated systolic hypertension [ISH; systolic blood pressure (SBP) > or = 160, diastolic blood pressure (DBP) < 90 mmHg, n = 19], diastolic +/- systolic hypertension (SDH; DBP > or = 90 mmHg, n = 10) and normotension (SBP < 160, DBP < 90 mmHg, n = 17). INTERVENTION: Four 14 day treatments, 50, 100, 200 and 300 mmol/day of sodium chloride supplementation interspersed with 14 day washout periods on a salt-restricted diet. MAIN OUTCOME MEASURES: The 24 h blood pressure, heart rate, weight, urinary sodium and creatinine clearance measured during baseline, treatment and washout periods and angiotensinogen (AGT) and angiotensin converting enzyme (ACE) genotypes. RESULTS: For the entire cohort, the mean +/- standard error (SE) of change from baseline in SBP for 50, 100, 200 and 300 mmol/day salt was 7.7+/-2.4, 12.1+/-2.4, 16.6+/-3.0, 18.5+/-2.6 mmHg, respectively. For DBP, the respective changes were: -0.1+/-1.5, 2.4+/-1.6, 3.0+/-1.5, 5.8+/-1.7 mmHg. The increase in SBP among ISH subjects was significantly higher than among subjects in the SDH and normotensive groups (P < 0.05). AGT genotype influenced the effect of salt dose on the change in DBP (P = 0.006) but not SBP (P = 0.7). CONCLUSIONS: In healthy, older subjects, a linear increase in BP occurred with increasing salt dose, it appeared most pronounced in ISH subjects and could be modulated by AGT genotype.
Aged↗
Protective immunity and antibody-secreting cell responses elicited by combined oral attenuated Wa human rotavirus and intranasal Wa 2/6-VLPs with mutant Escherichia coli heat-labile toxin in gnotobiotic pigs.
Two combined rotavirus vaccination regimens were evaluated in a gnotobiotic pig model of rotavirus infection and disease and were compared to previously tested rotavirus vaccination regimens. The first (AttHRV/VLP2x) involved oral inoculation with one dose of attenuated (Att) Wa human rotavirus (HRV), followed by two intranasal (i.n.) doses of a rotavirus-like particle (2/6-VLPs) vaccine derived from Wa (VP6) and bovine RF (VP2) rotavirus strains. The 2/6-VLPs were coadministered with a mutant Escherichia coli heat-labile toxin, LT-R192G (mLT) adjuvant. For the second regimen (VLP2x/AttHRV), two i.n. doses of 2/6-VLPs+mLT were given, followed by one oral dose of attenuated Wa HRV. To compare the protective efficacy and immune responses induced by the combined vaccine regimens with individual rotavirus vaccine regimens, we included in the experiments the following vaccine groups: one oral dose of attenuated Wa HRV (AttHRV1x and Mock2x/AttHRV, respectively), three oral doses of attenuated Wa HRV (AttHRV3x), three i.n. doses of 2/6-VLPs plus mLT (VLP3x), three i.n. doses of purified double-layered inactivated Wa HRV plus mLT (InactHRV3x), mLT alone, and mock-inoculated pigs. The isotype, magnitude, and tissue distribution of antibody-secreting cells (ASCs) in the intestinal and systemic lymphoid tissues were evaluated using an enzyme-linked immunospot assay. The AttHRV/VLP2x regimen stimulated the highest mean numbers of intestinal immunoglobulin A (IgA) ASCs prechallenge among all vaccine groups. This regimen induced partial protection against virus shedding (58%) and diarrhea (44%) upon challenge of pigs with virulent Wa HRV. The reverse VLP2x/AttHRV regimen was less efficacious than the AttHRV/VLP2x regimen in inducing IgA ASC responses and protection against diarrhea (25% protection rate) but was more efficacious than VLP3x or InactHRV3x (no protection). In conclusion, the AttHRV/VLP2x vaccination regimen stimulated the strongest B-cell responses in the intestinal mucosal immune system at challenge and conferred a moderately high protection rate against rotavirus disease, indicating that priming of the mucosal inductive site at the portal of natural infection with a replicating vaccine, followed by boosting with a nonreplicating vaccine at a second mucosal inductive site, may be a highly effective approach to stimulate the mucosal immune system and induce protective immunity against various mucosal pathogens.
Adjuvants, Immunologic↗
Sex differences in bone mass acquisition during growth: the Fels Longitudinal Study.
Risk of osteoporosis in later life may be determined during adolescence and young adulthood. The present study used longitudinal data to examine the accumulation of bone mineral content (BMC) and bone mineral density (BMD) in Caucasian subjects ages 6-36 yr. Growth in BMC and BMD (measured by dual X-ray absorptiometry; Lunar, Madison, WI) of 94 males and 92 females was monitored for a mean period of 4.29 yr. The main findings were that there were no sex differences in BMC or BMD during the prepubertal stage; however, females had significantly higher BMD of the pelvis and BMC and BMD of the spine during puberty, and postpubertal males generally had significantly higher BMC and BMD than their female counterparts. In addition, the longitudinal rate of bone accumulation in both sexes increased rapidly during childhood and adolescence and was nearly complete at the end of puberty. Finally, peak BMC and BMD was achieved between the ages of 20 and 25 and occurred earlier in females than in males. The rates of growth and timing of peak bone mass as reported here define the crucial period during which intervention protocols should be developed for maximizing skeletal mass to prevent the development of osteoporosis.
Absorptiometry, Photon↗
[Fatigue and radiotherapy. Literature review].
Fatigue is a common complaint for the cancer patient during and after radiotherapy, according to the published studies. Fatigue is a subjective symptom mostly underestimated by oncologists and other care givers. Etiology is complex, poorly understood in spite of obvious causes like insomnia, nausea, pain, depression, psychological distress, anemia, hypothyroidism, menopause disturbances, treatment adverse effects. Fatigue presents multifactorial and multidimensional aspects. To evaluate it, many tools can be used as single-item, unidimensional and multidimensional instruments. Practically, the open discussion with the patient throughout radiotherapy is essential to define it. Taking charge fatigue requires its acknowledgment by radiotherapist, treatment of associated symptoms with a multidisciplinary approach.
Anemia↗
Association between breast cancer and bone mineral density: the Dubbo Osteoporosis Epidemiology Study.
BACKGROUND: The association between bone mineral density and breast cancer was investigated in a nested case-control study, involving 30 breast cancer cases and 120 controls, aged 68+/-6 (mean +/-S.D.) years, as part of the Dubbo Osteoporosis Epidemiology Study (Australia). METHODS: Bone mineral density (BMD, g/cm(2)) at the femoral neck and lumbar spine was measured by dual energy X-ray absorptiometry. Anthropometric data and reproductive history were collected by direct interview using a structured questionnaire. RESULTS: In univariate conditional logistic regression analysis, lower age at menarche, longer overall duration of lifetime ovulation and higher bone density were associated with higher risk of breast cancer. Among the breast cancer cases, 20% of subjects had lumbar spine BMD greater than 1.20 g/cm(2) (or 2.5 S.D. above the mean) compared with less than 1% of the controls. After adjusting for the effects of duration of lifetime ovulation and body mass index, each 0.1 g/cm(2) increase in lumbar spine and femoral neck BMD was associated with a 2.1-fold (95% CI: 1.3-3.4) and 1.5-fold (1.0-2.4) respectively, higher risk of breast cancer. Further adjustment for age at menarche, hormone replacement therapy, and parity did not alter the result. Thus, postmenopausal BMD, which is affected by lifetime exposure to estrogen, is also related to risk of breast cancer. Importantly, it is estimated that estrogen therapy in osteoporotic women, even if raising the risk of breast cancer by 70% as suggested by some studies, would not elevate their risk to the level experienced by their non-osteoporotic counterparts. CONCLUSION: While the mechanism of this relationship remains to be explored, these data support the concept that lifetime exposure to estrogen is an indicator of risk of both breast cancer and osteoporosis. However, the use of estrogen in osteoporosis treatment would not elevate the risk of breast cancer in osteoporotic women up to the level experienced by their non-osteoporotic counterparts.
Absorptiometry, Photon↗
Detection of the effects of dopamine receptor supersensitivity using pharmacological MRI and correlations with PET.
Receptor supersensitivity is an important concept for understanding neurotransmitter and receptor dynamics. Traditionally, detection of receptor supersensitivity has been performed using autoradiography or positron emission tomography (PET). We show that use of magnetic resonance imaging (MRI) not only enables one to detect dopaminergic supersensitivity, but that the hemodynamic time course reflective of this fact is different in different brain regions. In rats unilaterally lesioned with intranigral 6-hydroxydopamine, apomorphine injections lead to a large increase in hemodynamic response (cerebral blood volume, CBV) in the striato-thalamo-cortico circuit on the lesioned side but had little effect on the intact side. Amphetamine injections lead to increases in hemodynamic responses on the intact side and little on the lesioned side in the same animals. The time course for the increase in CBV after either amphetamine or apomorphine administration was longer in striatum and thalamus than in frontal cortex. (11)C-PET studies of ligands which bind to the dopamine transporter (2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane 1, 5-naphthalnendisulfonate, WIN 35, 428 or CFT) and D2 receptors (raclopride) confirm that there is a loss of presynaptic dopamine terminals as well as upregulation of D2 receptors in striatum in these same animals. Pharmacologic MRI should become a sensitive tool to measure functional supersensitivity in humans, providing a complementary picture to that generated using PET studies of direct receptor binding.
Amphetamine↗
Plasmodium falciparum: generation of a cDNA library enriched in sporozoite-specific transcripts by directional tag subtractive hybridization.
We have adapted the "directional tag subtractive hybridization" technique as a means of investigating stage-specific gene expression in Plasmodium falciparum. This technique utilizes unidirectional cDNA libraries cloned into separate lambda vectors and involves hydroxyapatite chromatographic separation of target antisense cDNA and driver sense strand cRNA followed by PCR amplification of cDNA sequences specific to the target stage. This technique enabled efficient subtraction of asexual blood stage sequences from a P. falciparum sporozoite cDNA library and led to identification of novel sporozoite sequences. This technique can be applied to study gene expression in parasite stages that are difficult to obtain routinely.
Animals↗
Deterioration in quality of life following hip fracture: a prospective study.
To examine longitudinal change in health-related quality of life (HRQoL) following hip fracture in elderly subjects, 32 patients with hip fractures and 29 sex-matched non-fracture control subjects (mean +/- SD age 82 +/- 8 and 86 +/- 6 years respectively) were enrolled in a prospective, case-control study. Fracture subjects completed a generic questionnaire, Short Form 36 (SF-36), and a disease-targeted measure, the revised Osteoporosis Assessment Questionnaire (OPAQ2), on two separate occasions, within 1 week of fracture and 12-15 weeks after fracture. Controls completed both questionnaires on two occasions 12 weeks apart. SF-36 scores were significantly correlated with OPAQ2 in comparable domains of Physical Function (r = 0.76), General Health (r = 0.70) and Mental Health/Tension (r=0.86). Control subjects had stable scores with the OPAQ2 and SF-36. At 3 months after fracture there was a significant reduction in HRQoL in the SF-36 domains Physical Function (-51%), Vitality (-24%) and Social Function (-26%) and in the OPAQ2 domains Physical Function (-20%), Social Activity (-49%) and General Health (-24%). Hip fracture patients thus had a lower baseline HRQoL and experienced a significant deterioration in HRQoL after hip fracture on both the SF-36 and OPAQ2. HRQoL should be part of a comprehensive assessment of the costs of osteoporosis including fracture-associated morbidity.
Aged↗
Associations between maternal peak bone mass and bone mass in prepubertal male and female children.
The aim of this study was to estimate heritability of bone density in premenopausal women, prepubertal male, and prepubertal female child pairs. We studied 291 pairs (mothers, mean age, 33 years, range 22-45 years; children, mean age, 7.92 years, range 7.32-8.92 years). Bone density and body composition were assessed by dual-energy X-ray absorptiometry. Height and weight were measured in both mother and child. Body size-adjusted heritability estimates for areal bone density (g/cm2) were all statistically significant (femoral neck, 59%; lumbar spine, 38%; total body, 41%) and were consistently and significantly higher in mother-daughter pairs (n = 105) as compared with mother-son pairs (n = 186). Heritability estimates for bone mineral apparent density (BMAD; g/cm3) were marginally lower but remained statistically significant at all sites (femoral neck, 51%; lumbar spine, 32%; total body, 38%). Maternal osteopenia was associated with significant reductions in bone mass at all sites in the children (femoral neck, 0.75 SD and p < 0.0001; lumbar spine, 0.61 SD and p < 0.0001; total body, 0.43 SD and p = 0.012). Mother-child bone areal bone density correlation coefficients and prediction of low bone mass in the child were greater (but this did not reach statistical significance) if the corresponding anatomical site in the mother was used for prediction with the exception of the total body. These data confirm that heritability of bone mass extends to prepubertal children and is gender- and possibly site-specific as well as under separate genetic control to growth. Furthermore, the strength of the mother-child association is such that bone density screening of mothers would make it possible to identify most prepubertal children at higher risk of osteoporosis in later life.
Absorptiometry, Photon↗