Telemedicine applications clear time and distance barriers easily.
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Delivery of Health Care, Integrated↗
Biomedical subjects
L Smith
Publications and source records attributed to L Smith.
Labor immigration and capital flows: long-term Australian, Canadian and United States experience.
"Evidence on labor immigration and capital inflows to three high labor-immigration economies (Australia, Canada, the United States) is examined over periods ranging from 1820-1870 through to 1991. Data show a close association between capital flows and immigration, although causality implications are ambiguous. For the United States, the relation between factor flows is more complex than for the other countries, but flows to the United States have influenced those to smaller economies. All three nations have been subjected to common immigrant push factors through to 1930-1950 but, since World War II, linkages between factor flows have altered. Post-World War II U.S. immigration restrictions have become more important as a global determinant of labor flows, with factor flow policymaking becoming increasingly internationally interdependent."
Americas↗
ABT-431: the diacetyl prodrug of A-86929, a potent and selective dopamine D1 receptor agonist: in vitro characterization and effects in animal models of Parkinson's disease.
(-)-Trans 9,10-hydroxy-2-propyl-4,5,5a,6,7,11b-hexahydro-3-thia-5- azacyclopent-1-ena[c]phenanthrene hydrochloride (A-86929) is a potent and selective full agonist at the dopamine (DA) D1-like receptor. Judging by its binding affinities to the D1 and D2 classes of receptors, the compound is approximately 20-fold D1 receptor-selective, whereas relative potencies based on functional in vitro assays indicate that A-86929 is greater than 400-fold D1-selective. A-86929 has moderate to weak (Ki > 1 microM) affinity at other monoaminergic and peptidergic receptors, at ion channels and at monoamine uptake sites. The catechol of A-86929 was bis-acetylated to produce the prodrug, (-)-trans 9,10-acetoxy-2-propyl-4,5,5a,6,7,11-b-hexahydro-3-thia- 5-azacyclopent-1-ena[c]phenanthrene hydrochloride (ABT-431), which is more chemically stable yet is rapidly converted to the parent compound with a half-life of less than 1 min in plasma. Both A-86929 and ABT-431 produced contralateral rotation in rats bearing unilateral 6-hydroxydopamine lesions, with ED50 values of 0.24 mumol/kg s.c. and 0.54 mumol/kg s.c., respectively. A-86929 and ABT-431 improved behavioral disability scores and increased locomotor activity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned marmoset model of Parkinson's disease in a dose-dependent manner (the minimum effective dose was 0.10 mumol/kg s.c.). When administered three times daily for 30 consecutive days to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned marmosets, A-86929 significantly improved disability scores throughout the duration of the study. Current Parkinson's disease therapy includes L-dopa, which stimulates both classes of DA receptors by virtue of its conversion to DA in vivo, and direct-acting D2-selective agonists. Stimulation of the D2 receptor, which is associated with all current DA agonist-based therapies, may contribute to their dose-limiting side effects. An agent such as A-86929 (or its prodrug ABT-431), which selectively stimulates the D1 receptor, may represent a novel mechanism for Parkinson's disease therapy with the potential for an improved side-effect profile and, consequently, improved patient compliance.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Changes in permeability of sheep's lungs by oleic acid are dose dependent.
OBJECTIVE: To evaluate a two-isotope technique to detect graded changes in pulmonary microvascular permeability. DESIGN: Open experimental study. SETTING: University hospital, Sweden. MATERIAL: Fifty-seven sheep. INTERVENTIONS: Catherisation of one carotid artery, pulmonary artery and central vein. Control group 1 (n = 10), control group 2 (n = 12) had an additional pulmonary artery balloon catheter inserted, experimental group 3 (n = 9) was given oleic acid 0.005 mg kg-1 BW, experimental group 4 (n = 12) received oleic acid 0.02 mg kg-1 BW and experimental group 5 (n = 11) 0.05 mg kg-1 BW. Groups 3-5 had all PA catheters. All animals were intubated and ventilated artificially. Duration of experiments was 6 hours. OUTCOME MEASURES: Transferrin was labelled in vivo with 113mIn chloride and erythrocytes with 99mTc following injection of stannous chloride. External gamma counting was corrected for background, decay and scatter. Blood activity was used as reference. Normalised slope index (NSI) and transferrin leak index (TLI) were calculated as measures of pulmonary microvascular permeability. RESULTS: A graded response in both NSI and TLI was found. Insertion of the PA catheter (group 2) significantly increased NSI from (group 1) (1.4 (0.1)) 10(-4) min-1 to (11 (2)) 10(-4) min-1 (p < 0.05). TLI increased significantly from (9 (2)) 10(-4) min-1 to (72 (13)) 10(-4) min-1. Oleic acid increased NSI significantly to (13 (1)) 10(-4) min-1, (32 (2)) 10(-4) min-1 and (61 (5)) 10(-4) min-1 in groups 3-5, respectively. Corresponding values for TLI were (95 (13)) 10(-4) min-1, (162 (6)) 10(-4) min-1 and (228 (26)) 10-4 min-1, respectively. CONCLUSION: The double-isotope technique of external monitoring of permeability changes to protein in the lungs was sensitive to pick up graded increments in leakage, related in a dose-dependent way to lung injury.
Animals↗
Clinical evaluation of a peritoneal dialysis kinetic modeling set.
A closed system kinetic modeling set (KMS) has been fabricated which permits collection of a small 100-mL aliquot from each exchange. The KMS was used to collect aliquots from 65 exchanges in 13 patients. The concentrations of urea nitrogen (UN), creatinine (Cr), glucose (G), and total protein (TP) were measured in each individual aliquot (Cka) and drain bag (Cba), and all aliquots for each dialysis treatment were used to calculate the concentrations expected in total batched dialysate (BaC) for the treatment and were compared to the measured concentrations (BaM) in mixed total dialysate. The ratios Cka/Cba [mean+/- two times coefficient of variation (mean +/- 2CV)] were 1.00 +/- 5%, 1.00 +/- 5%, 1.01 +/- 10%, and 1.00 +/- 6%, respectively, for UN, Cr, G, and TP (each, n = 61). The ratios BaC/BaM (mean +/- 2CV) were 1.00 +/- 2%, 1.00 +/- 5%, 1.01 +/- 3%, and 0.99 +/- 5%, respectively, for UN, Cr, G, and TP (each, n = 15). We concluded that the KMS aliquots can be reliably used for kinetic and total clearance calculations without mixing and transporting large volumes of dialysate.
Blood Glucose↗
A challenge to Lancet readers.
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International Cooperation↗
Trypanosomatid cysteine protease activity may be enhanced by a kininogen-like moiety from host serum.
African trypanosomes contain cysteine proteases (trypanopains) the activity of which can be measured by in vitro digestion of fibrinogen, after electrophoresis in fibrinogen-containing SDS/polyacrylamide gels. When assessed by this procedure, trypanopain from Trypanosoma brucei (trypanopain-Tb) is estimated to have a molecular mass of 28 kDa. However, two additional bands of trypanopain activity (87 kDa and 105 kDa) are observed if serum is added to the trypanopain before electrophoresis. Formation of the 87 and 105 kDa bands is frequently accompanied by a reduction in the intensity of the 28 kDa activity which suggests that the extra bands are complexes of the 28 kDa trypanopain-Tb and a molecule from rat serum called rat trypanopain moledulator (rTM). The rTM-induced activation of cysteine proteases is not restricted to T. brucei as it is also observed with proteases from other protozoan parasites such as bloodstream forms of Trypanosoma congolense and the mammalian-infective in vitro-derived promastigote forms of Leishmania donovani and Leishmania major. The physical properties of rTM resemble those of the kininogen family of cysteine protease inhibitors. rTM is an acidic (pI 4.7) heat-stable 68 kDa glycoprotein with 15 kDa protease-susceptible domains. This resemblance between rTM and kininogens was confirmed by the positive, albeit weak, immunoreactivity between anti-(human low-molecular-mass kininogen) antibody and rTM as well as anti-rTM antibody and human low-molecular-mass kininogen. Furthermore, commercial preparations of human-low-molecular-mass kininogen and chicken egg white cystatin mimicked rTM by forming extra bands of proteolytic activity in the presence of trypanopain-Tb. In some instances, low-molecular-mass kininogen was also observed to increase the rate of hydrolysis of 7-(benzyloxycarbonyl-phenylalanyl-arginyl-amido)-4- methylcoumarin by live T. brucei. Although this effect was rather erratic, in no instance was significant inhibition observed when this putative cysteine protease inhibitor was used under these conditions. The activation of parasite cysteine proteases by commonly accepted cysteine protease inhibitors is unexpected and may have important pathological repercussions.
Animals↗
Chronic L-DOPA administration induces dyskinesias in the 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine-treated common marmoset (Callithrix Jacchus).
Dyskinesias occur in the majority of patients with Parkinson's disease chronically treated with L-DOPA and also occur in several nonhuman primate species after 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) and L-DOPA treatment. The common marmoset (Callithrix jacchus) shows parkinsonian motor deficits after MPTP administration, and we now report dyskinesias occurring in this species during chronic L-DOPA exposure. Marmosets rendered chronically parkinsonian after MPTP administration were treated orally with L-DOPA plus carbidopa for 3 weeks. After several days the animals began to display chorea, choreoathetosis, and dystonia. The severity of dyskinesias varied between the animals, with the most severely parkinsonian animals displaying the most dyskinetic movements. Each animal showed an idiosyncratic pattern of dyskinesias, which was highly reproducible. These L-DOPA-primed animals also received other D2 D1, and mixed D1/D2 agonist drugs. Quinpirole, bromocriptine, pergolide, apomorphine, and A-77636 all produce dyskinesias that were identical in character to those seen after L-DOPA administration, but the D1 agonist A-77636 gradually abolished dyskinesias while preserving its antiparkinsonian activity. The MPTP-treated marmoset provides a useful model in which to study dyskinesias in Parkinson's disease and to examine new therapeutic strategies aimed at alleviating this common side effect of chronic dopamine replacement therapy.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Lack of apparent antipsychotic effect of the D1-dopamine receptor antagonist SCH39166 in acutely ill schizophrenic patients.
SCH 39166 is the first selective D1 dopamine receptor antagonist developed for the treatment of schizophrenic patients. To examine potential antipsychotic effect, tolerability and safety, SCH 39166 was given orally to 17 acutely ill drug free schizophrenic patients (DSMIIIR) in an open 4-week study. Doses were escalated from 10 to 100 mg b.i.d. according to a fixed schedule over 17 days and remained at 100 mg b.i.d. for another 11 days. The drug was withdrawn prematurely in ten patients because of deterioration or refusal to take SCH 39166. In the nine patients participating for more than 2 weeks, none had an apparent reduction of BPRS or CGI scores. Side effects were agitation, akathisia and emesis in single patients. After withdrawal of SCH 39166 of the patients improved when treated with classical neuroleptics or clozapine. The result of the study does not support the prediction that selective D1 dopamine receptor antagonism will produce antipsychotic effects in schizophrenia.
Adult↗
Effect of heparin anticoagulation on neutrophil adhesion molecules and release of IL8: C3 is not essential.
OBJECTIVE: To examine the role of heparin in modulating neutrophil activation and release of cytokine. BACKGROUND: Up-regulation of CD11b, down-regulation of L-selectin on neutrophil cell surface and release of IL8 occur in response to extracorporeal circulation (ECC) and were proposed to cause leakage of the capillaries in patients. DESIGN: In a series of experiments, we examined the effect of heparin (4 U/ml) comparing it with ethylenediamine tetra-acetate (EDTA, 1.5 mg/ml) and citrate mixture (100 microliters/ml), heparin dose-response, IL8 (human recombinant IL8) dose-response and protamine (80 micrograms/ml) neutralisation of heparin (4 U/ml) using donor blood (total of 38). The role of complement component type 3 (C3) was tested. Neutrophils from a patient with complete C3 deficiency were stimulated by using heparin and cobra venom factor (10 micrograms/ml) and compared with controls (n = 5). CD11b and L-selectin expressions were assayed immediately and serially up to 120 min using immune fluorescence and flow cytometry. Serum concentrations of IL8 were determined by using enzyme-linked immunosorbent assay. RESULTS: The medians of up-regulation of CD11b were 540.2 (range 235.2-653.3) for heparin vs. 186.5 (55.7-207.1) for EDTA and 192.5 (69.2-263.8) for citrate mixture, P < 0.01. The medians of down-regulation of L-selectin were 79 (32-192) for heparin vs. 18.4 (0-188) for EDTA and 36.2 (7.4-135) for citrate mixture, P < 0.05. Up-regulation of CD11b, down-regulation of L-s and release of IL8 were inversely related to heparin concentration (r = 0.87, P < 0.05). Serum concentration of IL8 had a direct relationship to the changes in CD11b and L-selectin expression (r = 0.92). Heparin-protamine complex was less stimulant to expression of CD11b and L-selectin than heparin or protamine (P < 0.05). In blood samples from C3-deficient patients, heparin and cobra venom factor caused up-regulation of CD11b and down-regulation of L-selectin similar to that of controls (P > 0.05). CONCLUSIONS: Heparin stimulates up-regulation of neutrophil adhesion molecules CD11b, down-regulation of L-selectin and release of IL8. These effects are inversely related to heparin concentration and are independent of C3 activation. IL8 has a direct relationship to activation of neutrophil adhesion molecules. Increasing heparin dosage reduces neutrophil activation and may reduce the morbidity of patients.
Adolescent↗
The use of twice daily nedocromil sodium in the treatment of asthma.
The efficacy and safety of nedocromil sodium inhalation aerosol (4 mg of Tilade administered by metered-dose inhaler) given twice daily was compared with placebo in 112 patients with mild-to-moderate asthma who had been receiving maintenance therapy with oral or inhaled bronchodilators or both. After a 2-week run-in period and a subsequent 2-week baseline period, patients were randomized to active treatment (n = 56) or placebo (n = 56) for 8 weeks. All maintenance bronchodilators were withdrawn before the baseline period, and patients entered the treatment period only after demonstrating a specified level of asthma symptoms. Twice daily administration of nedocromil sodium improved all asthma symptoms in these patients who had symptoms as a result of the withdrawal of their maintenance theophylline and/or oral and inhaled beta 2-agonist bronchodilators. During the primary time period (treatment weeks 5 to 8), statistically significant between-group differences favored nedocromil sodium for the asthma summary score (primary variable, p = 0.001), daytime asthma (p = 0.001), and sleep difficulty caused by asthma (p = 0.006). Furthermore, significant reductions in the use of as-needed rescue medications were reported in the nedocromil sodium group (p = 0.003) compared with the placebo group. Final overall opinions of treatment effectiveness expressed by physicians (p = 0.016) and patients (p = 0.002) strongly favored nedocromil sodium.
Administration, Inhalation↗
Recovery from work shifts: how long does it take?
Although regulations on work hours usually include a minimum weekly rest period, there is little empirical evidence concerning recovery from work. Shift-working nurses (N = 61) used a handheld computer for 28 days to complete self-ratings, cognitive-performance tasks, and a sleep diary. Many measures were worse on rest days that followed a night shift rather than a day shift and tended to be worse on first rest days compared with subsequent rest days. Alertness was lowest on the 1st rest day following a night shift. Social satisfaction was better on workdays that were preceded by 2 rather than 1 rest day. Reaction time decreased over consecutive night shifts and tended to increase over rest days following night shifts. The results are interpreted as being consistent with the combined adaptive costs of fatigue and adjustment to and from a nocturnal routine. The practical implications for scheduling rest days are considered.
Adult↗
Microcell mediated chromosome transfer maps the Fanconi anaemia group D gene to chromosome 3p.
Fanconi anaemia (FA) is an autosomal recessive disorder characterized by progressive pancytopenia, short stature, radial ray defects, skin hyperpigmentation and a predisposition to cancer. Cells from FA patients are hypersensitive to cell killing and chromosome breakage induced by DNA cross-linking agents such as mitomycin C (MMC) and diepoxybutane (DEB). Consequently, the defect in FA is thought to be in DNA crosslink repair. Additional cellular phenotypes of FA include oxygen sensitivity, poor cell growth and a G2 cell cycle delay. At least 5 complementation groups for Fanconi anaemia exist, termed A through E. One of the five FA genes, FA(C), has been identified by cDNA complementation, but no other FA genes have been mapped or cloned until now. The strategy of cDNA complementation, which was successful for identifying the FA(C) gene has not yet been successful for cloning additional FA genes. The alternative approach of linkage analysis, followed by positional cloning, is hindered in FA by genetic heterogeneity and the lack of a simple assay for determining complementation groups. In contrast to genetic linkage studies, microcell mediated chromosome transfer utilizes functional complementation to identify the disease bearing chromosome. Here we report the successful use of this technique to map the gene for the rare FA complementation group D (FA(D)).
Cell Line↗
Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate.
High concentrations of nitrite present in saliva (derived from dietary nitrate) may, upon acidification, generate nitrogen oxides in the stomach in sufficient amounts to provide protection from swallowed pathogens. We now show that, in the rat, reduction of nitrate to nitrite is confined to a specialized area on the posterior surface of the tongue, which is heavily colonized by bacteria, and that nitrate reduction is absent in germ-free rats. We also show that in humans increased salivary nitrite production resulting from nitrate intake enhances oral nitric oxide production. We propose that the salivary generation of nitrite is accomplished by a symbiotic relationship involving nitrate-reducing bacteria on the tongue surface, which is designed to provide host defence against microbial pathogens in the mouth and lower gut. These results provide further evidence for beneficial effects of dietary nitrate.
Adult↗
Rett syndrome--distribution of phenotypes with special attention to the preserved speech variant.
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Child↗
The use of survey measures to assess circadian variations in alertness.
Current models of sleep regulation postulate both a homeostatic and circadian component and promise an understanding of disturbed and displaced sleep. Estimates of these components have traditionally required relatively cumbersome and costly measures, including sleep electroencephalograms and continuously recorded rectal temperature, but it has recently been demonstrated that they may successfully be based on frequent (e.g. 2-hourly) concurrent ratings of alertness. This paper examines whether similar results might be obtained using retrospective survey measures of alertness obtained from shiftworking nurses at a single sitting. These retrospective measures are shown to be sensitive to both time of day and shift, to have a high level of reliability even for relatively small sample sizes (e.g. 10) and to be valid predictors of more traditional concurrent measures of alertness. It is concluded that retrospective alertness ratings may prove to be an extremely cost-effective method for examining the trends in alertness in various groups, including those suffering from specific types of sleep disorder.
Adult↗
The effect of amoxycillin on salivary nitrite concentrations: an important mechanism of adverse reactions?
Broad spectrum antibiotics are known to predispose towards oral candidiasis and gastroenteritis. Oral nitrite synthesis by commensal bacteria may be important in protecting the mouth and lower intestine from pathogenic organisms, including Candida albicans. The effect of 2 days administration of the broad spectrum antibiotic amoxycillin on salivary nitrite concentration, following a 200 mg potassium nitrate oral load, was studied in 10 healthy volunteers. The Cmax fell by 40% and the AUC was reduced by 1227 microM h (43%, 95% CI 273, 2181, P < 0.006) in the antibiotic treated group when compared with control. These findings suggest that destruction of nitrate reductase containing bacteria in the mouth by antibiotics may explain an increased incidence of infection with Candida and other pathogens.
Adult↗
Record linkage in Australian epidemiological research: health benefits, privacy safeguards and future potential.
Epidemiologists are increasingly concerned with the health effects of interventions and of exposure to noninfectious agents, but there may be long periods between exposure and outcome. Collecting information from respondents is a costly and often inefficient way of obtaining the longitudinal data necessary to study these effects. Linking existing data can be an effective and efficient alternative. However, it is often not practicable to obtain informed consent from the individuals whose records are to be linked. This raises important issues relating to protection of privacy. This paper examines the health benefits and privacy issues of epidemiological and health services research involving record linkage in Australia. The future potential for studies based on record linkage is discussed in the context of recent national and international developments in data protection. In the interests of public health and the rational use of health resources a balance must be struck between protecting individual privacy and conducting such health research for the common good.
Australia↗