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Biomedical subjects

J A Cross

Publications and source records attributed to J A Cross.

17 recordsLinked to original sources

Numerical modelling of the accommodating lens.

Data on geometric and material properties of the human lens derived from various published sources are used to construct axisymmetric, large displacement, finite element models of the accommodating lens of subjects aged 11, 29 and 45 years. The nucleus, cortex, capsule and zonule are modelled as linearly elastic materials. The numerical model of the 45-year lens is found to be significantly less effective in accommodating than the 29-year lens, suggesting that the modelling procedure is capable of capturing at least some of the features of presbyopia. The model of the 11-year lens shows some anomalous behaviour, and reasons for this are explored.

Accommodation, Ocular↗

Modelling the transmission dynamics of Ross River virus in Southwestern Australia.

During the 1995-1996 Australian financial year, over 1300 notifications of Ross River (RR) virus disease were notified in humans from Southwestern Australia. Due to the mild symptoms of the disease, it is difficult to diagnose and subclinical infections are common. However, these subclinical infections do give rise to immunity. For planning and control, it is important for public health authorities to estimate the true number of people who have contracted the disease and to assess the impact of key epidemiological parameters. A mathematical model was developed to describe the transmission of RR virus between its hosts (humans and kangaroos) and its vectors (mosquitoes). For this model, the threshold conditions and relative removal rates were calculated and interpreted. Finally, a computer program was written to simulate the model in order to estimate the total number, both clinical and sub clinical human infections given known and hypothetical epidemiological parameter values. Within this simulation sensitivity of the results to changes in the parameters were examined. The analysis of the threshold conditions conformed well to established principles of arboviral transmission and control. It was observed that conditions which can prevent an outbreak occuring include reducing the number of susceptibles in host and vector populations, reducing the infection rates between hosts and vectors and shortening the duration of viraemia. Results on the sensitivity analysis showed that some parameters such as the extrinsic incubation period, mosquito mortality rate in winter and the proportion of Western Grey Kangaroos in the marsupial population have little effect on human incidence. However, the transmission rate between hosts and vectors, vector-mortality rate in summer and the proportion of infectious vectors among infected vectors have pronounced effects. The simulation results on the ratio of clinical to subclinical human infections predicted a minimum ratio of 1:2 and a maximum ratio of 1:65, which is consistent with data obtained during previous sero-epidemiological studies.

Alphavirus Infections↗

Folate-binding triggers the activation of folylpolyglutamate synthetase.

Folic acid is an essential vitamin for normal cell growth, primarily through its central role in one-carbon metabolism. Folate analogs (antifolates) are targeted at the same reactions and are widely used as therapeutic drugs for cancer and bacterial infections. Effective retention of folates in cells and the efficacy of antifolate drugs both depend upon the addition of a polyglutamate tail to the folate or antifolate molecule by the enzyme folylpolyglutamate synthetase (FPGS). The reaction mechanism involves the ATP-dependent activation of the free carboxylate group on the folate molecule to give an acyl phosphate intermediate, followed by attack by the incoming L-glutamate substrate. FPGS shares a number of structural and mechanistic details with the bacterial cell wall ligases MurD, MurE and MurF, and these enzymes, along with FPGS, form a subfamily of the ADP-forming amide bond ligase family. High-resolution crystallographic analyses of binary and ternary complexes of Lactobacillus casei FPGS reveal that binding of the first substrate (ATP) is not sufficient to generate an active enzyme. However, binding of folate as the second substrate triggers a large conformational change that activates FPGS and allows the enzyme to adopt a form that is then able to bind the third substrate, L-glutamate, and effect the addition of a polyglutamate tail to the folate.

Adenosine Triphosphate↗

Prevention of hypercalcaemic nephropathy and tissue calcification by glucagon during phosphate infusion.

Patients with serum calcium above 4.5 mmol/litre risk sudden death. Rehydration and frusemide may decrease calcium levels by 0.5-1 mmol/litre but result in a high renal filtered load of calcium which, if above 3.7 mmol/litre, causes calcium phosphate protein complexes to form giving rise to hypercalcaemic nephropathy. Current drugs namely clodronate, calcitonin and plicamycin take days to lower serum calcium and have disadvantages. Intravenous phosphate rapidly lowers serum calcium but when the calcium phosphate product rises above 4.6 mmol/litre the saturation point for the precipitation of calcium hydrogen phosphate is reached and tissue calcification occurs. Intravenous glucagon results in a steep reduction in serum phosphate within minutes and also lowers serum calcium, resulting in a marked fall in the calcium phosphate product to well below the critical level of 4.6 mmol/litre. If, in addition to glucagon, intravenous phosphate is now given, it should have a further calcium-lowering effect by inhibiting bone osteoclasts.

Calcinosis↗

Mechanical equipment injuries in small manufacturing businesses. Knowledge, behavioural, and management issues.

This paper presents findings from an extensive study into factors that impact upon the high rate of injuries due to mechanical equipment, especially in small manufacturing firms. Issues relating to knowledge of health and safety issues and to management practices have been shown to be extremely important with regards to safety in small businesses. Knowledge and awareness of hazards were found to be relatively low and few respondents, especially managers, had received adequate safety training. Managers did not regard the identification and control of risks as a priority. Workplaces generally lacked effective safety management procedures such as safety rules and regulations, procedures for recording and learning from accidents, and clearly defined responsibilities for safety. Some issues requiring further investigation, and some recommendations for improving safety in small businesses, are presented.

Accidents, Occupational↗

Quality of life at baseline: is assessment after randomization valid? The AVID Investigators. The Antiarrhythmics Versus Implantable Defibrillators.

OBJECTIVES: The purpose of this report is to examine whether differences existed between patients who completed a baseline quality of life (QoL) form before being informed about their randomized assignments versus those who completed it after knowing their randomization assignments. METHODS: In the pilot phase of the Antiarrhythmics Versus Implantable Defibrillators (AVID) study (n = 200), 113 patients completed a baseline QoL battery prior to randomization (drug versus defibrillator), 49 additional patients completed this battery after randomization, and 38 patients did not complete this battery. Baseline demographic, clinical and QoL data were compared for these groups. RESULTS: Although the two groups with QoL data were not significantly different regarding various clinical and demographic characteristics, they did have significantly different QoL profiles. Patients with QoL collected before randomization had better overall QoL scores and mental health scores. CONCLUSIONS: These data suggest that patients with worse QoL may be less willing to complete a baseline QoL form in a timely manner or that knowledge of the randomization assignment may have an effect on QoL.

Aged↗

Pharmacologic management of heart failure: positive inotropic agents.

The use of positive inotropic agents in the acute and chronic treatment of heart failure is associated with a variety of hemodynamic effects. The beneficial effects of these agents, however, are not without associated adverse effects. An increase in cardiac output is achieved through diverse pharmacologic mechanisms of action depending on the specific inotropic agent. Digitalis glycosides, beta-adrenergic agonists, and phosphodiesterase inhibitors are described.

Cardiotonic Agents↗

Atrioventricular block.

The presentation of atrioventricular block in the critical care setting and the assessment parameters that the critical care nurse may use to aid in the determination of the severity of atrioventricular block are described. The underlying pathophysiology of atrioventricular block is examined to enhance the nurse's understanding of the rationale for intervention versus observation.

Critical Care↗

Percutaneous cardiopulmonary bypass support: a new approach to high-risk angioplasty.

Percutaneous cardiopulmonary bypass is a new technique for supporting systemic blood flow during high-risk coronary angioplasty procedures. This mechanical alternative, unlike traditional methods, is not limited by dependency on adequate left ventricular stroke volume. Percutaneous cardiopulmonary bypass support offers new and demanding challenges in the care of this high-risk group of patients.

Angioplasty, Balloon, Coronary↗

Brain GABAB binding sites in depressed suicide victims.

Binding sites for gamma-aminobutyric acid, type B (GABAB), were measured in post-mortem brain samples (frontal cortex, temporal cortex, and hippocampus) from a group of suicide victims and a group of sex- and age-matched controls. Retrospective psychiatric diagnosis was performed, and only suicide victims with clear evidence of depression in the absence of symptoms of other psychiatric or neurological disorders were studied. There were no significant differences between depressed suicides and controls in the number or affinity of GABAB binding sites in the frontal or temporal cortex and no difference in GABAB binding (measured at two concentrations) in the hippocampus. Thirteen of the depressed suicides had not been prescribed antidepressant drugs recently, and none were found in their blood at postmortem. The number of GABAB binding sites in the frontal and temporal cortex and GABAB binding in the hippocampus did not differ significantly between these drug-free suicides and matched controls. The Kd was higher, however, in the temporal cortex of the drug-free suicides than in the controls. A significant negative correlation was found between age and the number of GABAB binding sites in the temporal cortex (on the basis of pooled data from suicides and controls). These results indicate that GABAB binding sites are unaltered in the brains of depressed suicide victims.

Adolescent↗

Effects of chronic oral administration of the antidepressants, desmethylimipramine and zimelidine on rat cortical GABAB binding sites: a comparison with 5-HT2 binding site changes.

1. The effects of chronic oral administration of desmethylimipramine (DMI) or zimelidine (1.25 and 5 mg kg-1 twice daily for 21 days) were studied on rat whole cortical gamma-aminobutyric acidB (GABAB) binding sites. No changes in receptor affinity or number were found with either drug. 2. A subsequent study of GABAB binding sites using higher doses of these drugs (5 and 10 mg kg-1) and rat frontal cortex was also without effect, when investigated 24 h after termination of drug administration or 72 h after DMI administration (5 mg kg-1). 3. The number of frontal cortical 5-hydroxytryptamine2 (5-HT2) binding sites was significantly and dose-dependently decreased after both drugs, whereas the number of hippocampal 5-HT2 binding sites was not significantly altered after either drug. 4. As the number of frontal cortical GABAB binding sites was unaltered whereas the number of 5-HT2 binding sites was significantly decreased under identical study conditions, it may be concluded that the effects of antidepressant administration upon GABAB binding sites is a less consistent observation than their effects on 5-HT2 binding sites.

Animals↗

Are increases in GABAB receptors consistent findings following chronic antidepressant administration?

Desmethylimipramine and zimelidine (10 mg/kg) were administered to rats once daily for 21 days. Chronic desmethylimipramine significantly reduced the number of 5HT2 binding sites in the frontal cortex but not hippocampus while chronic zimelidine did not affect 5HT2 binding in either brain region. The number and affinity of GABAB binding sites in the frontal cortex were unaltered by either drug.

Animals↗

Panuramine, a selective inhibitor of uptake of 5-hydroxytryptamine in the brain of the rat.

The neurochemical profile of the novel inhibitor of uptake of 5-hydroxytryptamine (5-HT) panuramine (Wy 26002) has been investigated in the rat. In vitro, panuramine was found to be a potent and selective inhibitor of uptake of 5-HT with an IC50 of 22 +/- 4 nM. The IC50 for inhibition of uptake of noradrenaline was 848 nM and that for uptake of dopamine greater than 10 micron. Panuramine, in concentrations up to 10 micron did not displace the specific binding of either [3H]spiroperidol or [3H]5-HT and had no effect on the spontaneous or potassium-evoked release of 5-HT, suggesting that the compound had little effect on serotonergic transmission other than the inhibition of uptake of 5-HT. Panuramine also produced a dose-related antagonism of the depletion of 5-HT in brain induced by p-chloroamphetamine, confirming the ability of the drug to inhibit uptake of 5-HT in vivo.

Animals↗

Posture and the spread of extradural analgesia in labour.

Thirty-five patients kept in a sitting position for 5 min after a standard extradural injection in labour were compared with 54 patients maintained in the left lateral position throughout. The mean upper limit of analgesia was unchanged. A significant shift of the mean lower limit occurred in the sitting patients (P = 0.05, two-tailed), but contrary to classical teaching this was in a cephalad direction. Successful sacral blockade (analgesia at S234) and asymmetry of blockade occurred in a similar proportion of each group. It was concluded that the sitting position conferred no clinical advantage to patients receiving extradural analgesia in labour.

Anesthesia, Epidural↗