Vaccine preventable diseases and vaccination coverage in Australia, 1993-1998.
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Biomedical subjects
Publications and source records attributed to A Tucker.
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OBJECTIVE: This study examined a significant issue for chronic sexual abuse investigations: Children's eyewitness testimony about repeated events. The few previous studies focused on preschoolers and none used the present methodology of presenting repeated events differing slightly in their details, as would happen in chronic abuse. METHOD: One group of 6- to 7-year-olds played individually with an experimenter on one occasion; the other group experienced three such events, with some details remaining the same and others changing. In a phased interview, children were questioned about the initial event. RESULTS: For details which stayed the same, the children who experienced three events had more accurate memories. They had poorer memories than the single-event group for details which were changed in the later events; however, this was due to interference errors, with errors of omission and commission being lower than in the single-event group. Children conveyed clearly that inappropriate touching did not occur. CONCLUSIONS: Children who experience repeated events have increased recall for repeated details but confuse the timing of details which change across events. The findings support previous suggestions that (a) it is unrealistic to expect children to be able to report repeated events without some confusion about timing of details and (b) children are resistant to misleading questions about abuse.
BACKGROUND: Although extensively investigated, the mechanism(s) of post-spaceflight orthostatic intolerance has not been elucidated. Several researchers have proposed that the "trigger" for syncope is an empty ventricle, initiated when a hypercontractile state, possibly due to a sudden surge in epinephrine, causes the walls of the left ventricle to touch leading to a profound sympatho-inhibition and intense vagal stimulation. HYPOTHESIS: A markedly reduced left ventricular end systolic volume (LVESV) achieved during progressive, presyncopal-limited lower body negative pressure (LBNP) is the trigger for syncope. METHODS: Eight healthy men, age 25.1+/-1.3 yr, volunteered for the study. Changes in left ventricular end-diastolic volume and LVESV were measured, using two-dimensional echocardiography, at each stage of LBNP from rest up to presyncope (PS). Plasma venous catecholamine concentrations were measured at the end of each stage by high performance liquid chromatography (HPLC) with electrochemical detection. RESULTS: All subjects reached PS. Three men became bradycardic at presyncope while five remained tachycardic. LVESV decreased by 28% at PS with no evidence of ventricular cavity obliteration. Norepinephrine increased by 44% from rest to PS, but no epinephrine surge was detected (35% increase from rest to PS). CONCLUSION: These data indicate that it is possible to initiate syncope with only a 28% decrease in LVESV, and that sympatho-inhibition and bradycardia are not required elements for syncope to occur.
HYPOTHESIS: Space travel with exposure to microgravity leads to a significant reduction in orthostatic tolerance on return to Earth, for which countermeasures are only partially successful. The purpose of this study was to examine the effect of moderate dietary sodium restriction on tolerance to LBNP. METHODS: Eight healthy men, age 25.1+/-1.3 yr, volunteered for the study. Subjects were exposed to presyncopal LBNP after consuming their "typical" diet (C) for 5 d and after consuming a sodium restricted (SR) diet for 5 d. Diet sequence was randomized and adherence was verified by 24-h urine collection on the 4th and 5th days of each diet. RESULTS: All subjects reached presyncope during the LBNP, regardless of diet. Urinary sodium excretion was 3390+/-950 mg on the C diet and 1174+/-560 mg on the SR diet. Urinary potassium was not different between the diets. Cumulative stress index scores were 655+/-460 (mm Hg x min) on the C diet and 639+/-388 (mm Hg x min) during SR. Cardiac volumes, BP and total peripheral resistance were not different at any stage of the LBNP between the diets, nor were catecholamines. Plasma renin activity, determined by radioimmunoassay, was significantly higher during SR at rest, and during all stages of LBNP in comparison with the control diet. CONCLUSION: Moderate dietary sodium restriction is not detrimental to orthostatic tolerance.
PURPOSE: To investigate factors associated with medical students' use of infection control measures to protect themselves from HIV and other blood-borne infections. METHODS: All clinical students in the academic year of 1993-94 at the University of Washington, Seattle, were surveyed on the percent of time they use Universal Precautions (UPs), their sense of control and concern over HIV risk, estimates of occupational HIV risk and career plans. RESULTS: Responses of 294 students (86%) were studied. Most students use UPs most of the time but only 25% do so universally. Women (88.1%) use UPs more often than men (82.8%). Use of UPs was not related to the factors that actually predict risk of infection: incidence of exposure accidents and prevalence of HIV among patients. UP use was not associated with demographic characteristics of the student, specialty choice or level of concern about HIV. Students with greater sense of control over their risk reported greater use of UP. Those who plan to restrict patient services because of HIV risk use UP less often than others. CONCLUSION: Students use UPs but could do more to protect themselves. Infection control among young clinicians may be improved by education about the reality of the risk and the efficacy of precautionary measures.
BACKGROUND: Both echocardiographic and impedance cardiographic techniques have been used individually for the determination of stroke volume (SV) during lower body negative pressure (LBNP). Impedance cardiography has not been validated during LBNP. HYPOTHESIS: The purpose of this study was to determine both the absolute values for SV and the change in SV for each stage of LBNP using both impedance and echocardiographic techniques during staged LBNP to presyncope. The hypothesis was that there would be no difference between the two techniques for either the absolute values of SV or for the change in SV with each stage of LBNP. METHODS: There were 16 men who volunteered to undergo LBNP. LBNP was lowered in 10 mmHg stages for 5 min per stage until presyncope was reached. Left ventricular SV was determined by two-dimensional echocardiography and impedance cardiography. Both the absolute values for SV and the change in SV from baseline at each stage of LBNP were compared for the two methods. RESULTS: There were no significant differences between the two techniques for the measurement of either the absolute SV or the change in SV with LBNP. The two methods correlated highly with r = 0.89 for the absolute SV values and r = 0.93 for the change in SV. Graphical analysis with the Bland-Altman analysis showed little bias in the impedance measurement for SV (-0.031 ml) and the change in SV (-2.7 ml). CONCLUSIONS: Impedance cardiography was a reliable measure of SV, as well as the change in SV, during LBNP stress to presyncope.
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Reactions of cisplatin (cis-[PtCl2(NH3)2]) with albumin are thought to play an important role in the metabolism of this anticancer drug. They are investigated here via (i) labeling of cisplatin with 15N and use of two-dimensional 1H,15N NMR spectroscopy, (ii) comparison of natural human serum albumin with recombinant human albumin (higher homogeneity and SH content), (iii) chemical modification of Cys, Met, and His residues, (iv) reactions of bound platinum with thiourea, and (v) gel filtration chromatography. In contrast to previous reports, it is shown that the major sulfur-containing binding site involves Met and not Cys-34, and also a N ligand, in the form of an S,N macrochelate. Additional monofunctional adducts involving other Met residues and Cys-34 are also observed. During the later stages of reactions of cisplatin with albumin, release of NH3 occurs due to the strong trans influence of Met sulfur, which weakens the Pt-NH3 bonds, and protein cross-linking is observed. The consequences of these findings for the biological activity of cisplatin-albumin complexes are discussed.
OBJECTIVE: To investigate serum and follicular fluid insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) behavior in spontaneous and in superstimulated cycles. DESIGN: Estradiol, GH, IGF-I, and IGFBP-3 were evaluated in serum and in follicular fluid during spontaneous and stimulated cycles. SETTING: Department of Obstetrics and Gynecology, University of Naples, Naples, Italy. PATIENT(S): Ninety-two patients with regular menstrual cycles and tubal and/or male factor infertility undergoing treatment with an IVF program. INTERVENTION(S): The superstimulated IVF program uses leuprolide acetate suppression followed by hMG in a sequential manner in the subsequent cycle. After sufficient follicular development, hCG was administered, followed 34-36 hours later by oocyte retrieval. MAIN OUTCOME MEASURE(S): Growth hormone, IGF-I, and IGFBP-3 were assayed by RIA and immunoradiometric assay techniques. RESULT(S): Growth hormone levels in serum and in follicular fluid were higher after FSH-stimulated cycles than after physiologic cycles. Serum and follicular fluid IGF-I did not change during physiologic and FSH-stimulated cycles. Serum IGFBP-3 decreased only in FSH-stimulated cycles. Levels of IGFBP-3 in follicular fluid were lower than serum levels in late follicular phase both in physiologic and in FSH-stimulated cycles. CONCLUSION(S): Reduction of IGFBP-3 is an important mechanism allowing a larger local availability of free IGFs, which modulate the response of follicles to gonadotropin stimulation. This effect is amplified in stimulated cycles.
Circular dichroism and electron spin resonance spectroscopy are used to investigate the second specific metal binding site on human, bovine and porcine albumins. Ni(II), Zn(II) and Cd(II) can displace Cu(II) from the second Cu(II) site but not from the first strong site of human and bovine albumins (the N-terminal site). The second Cu(II) binds more strongly than the other metal ions to the second site of all three proteins, except Zn(II) binding to porcine albumin which is ca. 10 x stronger than Cu(II). The second Cu(II) site appears to be a tetragonal ¿2N, 4O¿ site.
Tremendous changes in pressure and flow occur in the pulmonary and systemic circulations after birth, and these hemodynamic changes should markedly affect endothelial cell replication. However, in vivo endothelial replication rates in the neonatal period have not been reported. To label replicating endothelial cells, we administered the thymidine analog bromodeoxyuridine to calves approximately 1, 4, 7, 10, and 14 days old before they were killed. Because we expected the ratio of replicating to nonreplicating cells to vary with vascular segment, we examined the main pulmonary artery, a large elastic artery, three sizes of intrapulmonary arteries, the aorta, and the carotid artery. In normoxia for arteries < 1,500 micron, approximately 27% of the endothelial cells were labeled on day 1 but only approximately 2% on day 14. In the main pulmonary artery, only approximately 4% of the endothelial cells were labeled on day 1 and approximately 2% on day 14. In contrast, in the aorta, approximately 12% of the endothelial cells were labeled on day 1 and approximately 2% on day 14. In chronically hypoxic animals, only approximately 14% of the endothelial cells were labeled on day 1 in small lung arteries and approximately 8% were still labeled on day 14. We conclude that the postnatal circulatory adaptation to extrauterine life includes significant changes in endothelial cell proliferation that vary dramatically with time and vascular location and that these changes are altered in chronic hypoxia.
We determined whether drugs which modulate the state of protein tyrosine phosphorylation could alter the threshold for high airway pressure-induced microvascular injury in isolated perfused rat lungs. Lungs were ventilated for successive 30-min periods with peak inflation pressures (PIP) of 7, 20, 30, and 35 cmH2O followed by measurement of the capillary filtration coefficient (Kfc), a sensitive index of hydraulic conductance. In untreated control lungs, Kfc increased by 1.3- and 3.3-fold relative to baseline (7 cmH2O PIP) after ventilation with 30 and 35 cmH2O PIP. However, in lungs treated with 100 microM phenylarsine oxide (a phosphotyrosine phosphatase inhibitor), Kfc increased by 4.7- and 16.4-fold relative to baseline at these PIP values. In lungs treated with 50 microM genistein (a tyrosine kinase inhibitor), Kfc increased significantly only at 35 cmH2O PIP, and the three groups were significantly different from each other. Thus phosphotyrosine phosphatase inhibition increased the susceptibility of rat lungs to high-PIP injury, and tyrosine kinase inhibition attenuated the injury relative to the high-PIP control lungs.
BACKGROUND: This study determined the efficacy of venoconstrictive thigh cuffs, inflated to 50 mmHg, on impeding fluid redistributions during simulated microgravity. METHODS: There were 10 healthy male subjects who were exposed to a 2-h tilt protocol which started in the standing position, and was followed by 30 min supine, 30 min standing, 30 min supine, 30 min of -12 degrees head down tilt (HDT, to simulate microgravity), 15 min of HDT with venoconstrictive thigh cuffs inflated, a further 10 min of HDT, 5 min supine, and 10 min standing. To increase the sensitivity of the techniques in an Earth-based model, 12 degrees HDT was used to simulate microgravity effects on body fluid shifts. Volume changes were measured with anthropometric sleeve plethysmography. RESULTS: Transition to the various tilt positions resulted in concomitant decrements in leg volume (Stand [STD] to Supine [SUP], -3.0%; SUP to HDT, -2.0%). Inflation of the venoconstrictive thigh cuffs to 50 mmHg, during simulated microgravity, resulted in a significant 3.0% increase in leg volume from that seen in HDT (p < 0.01). No significant changes in systemic cardiovascular parameters were noted during cuff inflation. CONCLUSIONS: We conclude that venoconstrictive thigh cuffs, inflated to 50 mmHg for 15 min during 12 degrees HDT, can create a more Earth-like fluid distribution. Cuffs could potentially be used to ameliorate the symptoms of cephalad edema seen with space adaptation syndrome and to potentiate existing fluid volume countermeasure protocols.
During development, growing motor axons are excluded from the ventral midline of the neural tube by diffusible chemorepellents emanating from this region. Molecular candidates for this chemorepellent activity include semaphorin D and netrin-1; the latter is known to repel trochlear motor axons. Qualitatively or quantitatively different responses to these molecules might underlie the initial deflection from the midline and subsequent segregation of motor axon trajectories. To test this idea, we have cocultured cell aggregates secreting netrin-1 or semaphorin D at a distance from tissue explants containing different motor neuron subpopulations, in collagen gels. Cranial motor axons that project dorsally in vivo such as those of the trigeminal, facial, and glossopharyngeal nuclei were repelled by both netrin-1 and semaphorin D. By contrast, ventrally projecting spinal motor axons and abducens axons were not affected by netrin-1. Spinal and abducens motor neurons also responded to semaphorin D. The ventrally projecting axons of oculomotor neurons were not repelled by netrin-1 or semaphorin D. Differential responsiveness to netrin-1 and semaphorin D could thus contribute to the generation of dorsal and ventral motor axon pathways during development.
The conserved Trp residue within helix 5 of the N-lobe of human serum transferrin (hTF/2N, 40 kDa) has been mutated to Tyr. NMR and CD spectra and energy calculations show that the mutation causes little perturbation of the overall structure of hTF/2N although the chelating agent Tiron removed Fe3+ from the mutant protein about three times faster than from wild-type hTF/2N. 1H-NMR resonances of residues in the Leu122-Trp128-Ile132 hydrophobic patch are assigned both by ring current calculations and with the aid of the mutation. [1H, 15N]-NMR resonances for 11 of the 14 Tyr residues were observed in the spectra of 15N-Tyr-hTF/2N and a resonance for Tyr128 was assignable in spectra of the mutant. The 15N resonance of Y128 was sensitive to oxalate and Ga3+ binding, and Ga3+ binding perturbed 15N resonances for most of the Tyr residues. Since these are well distributed over the N-lobe, it can be concluded that metal-induced structural changes are not merely local to the binding site.
Thickening of peripheral pulmonary arteries (PA) in the pulmonary hypertensive neonate has been well described morphologically, but less is known regarding the role of cell proliferation in either the normal or hypertensive neonatal PA. Thus we studied DNA synthetic indices in the tunica media and tunica adventitia of four different sizes/generations of PA in normoxic calves (n = 15) and calves exposed to hypobaric hypoxia (n = 15) during the first 14 days of life. DNA synthetic indices were determined by incorporation of the thymidine analogue bromodeoxyuridine (BrdU). Hemodynamic studies confirmed a steady decline in PA pressure in normal neonatal calves during the first 2 wk of life and progressive pulmonary hypertension in the hypoxic group. Lungs were perfusion-fixed and pulmonary arteries were evaluated for BrdU incorporation by immunohistochemistry. DNA synthetic indices (BrdU-labeled cells/1,000 cells) in the tunica media from normoxic calves were highest between 4 and 7 days postpartum and decreased to their lowest levels by day 14. The highest indices were observed in smaller generations of PA in the normoxic newborn. Adventitial cells exhibited the same general pattern of BrdU incorporation except that the postpartum peak occurred earlier, at 1 to 4 days. Exposure to hypoxia significantly increased (P = 0.001) DNA synthetic indices in both the tunica media and adventitia. The highest DNA synthetic indices were observed in smaller-generation vessels. These findings indicate that the fraction of cells traversing the S phase (i.e., actively replicating in the cell cycle) in the normal neonatal pulmonary vasculature during transition are initially high compared to reported rates in hilar PA from adult rats, but then decrease by 14 days after birth. Further, exposure to hypoxia during transition dramatically increases and prolongs pulmonary vascular cell proliferation. We conclude that structural remodeling in the hypertensive neonatal PA is due partly to increased cell proliferation in the tunica media and adventitia.
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