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Biomedical subjects

D Kenny

Publications and source records attributed to D Kenny.

At least 55 records · Page 3Linked to original sources

Relationship of clonogenic capacity to plating efficiency and vital dye staining of human periodontal ligament cells: implications for tooth replantation.

The survival rate of avulsed permanent teeth following replantation is affected primarily by the duration of the extra-alveolar period and the nature of the storage conditions. These factors are believed to strongly affect the viability of periodontal ligament (PL) cells but in vitro assays of cell viability based on vital dye assays are only weakly correlated with the tooth survival rate after replantation. The aim of the present study was to examine the relative dependence of cell membrane integrity, attachment and clonogenic capacity of human PL cells on the temperature and duration of the extra-alveolar period and the type of storage medium. Twenty-four premolar teeth were extracted for orthodontic reasons from 9 patients 11-18 years of age. Teeth were maintained at 4 degrees C or 23 degrees C for 15, 30, 60 or 120 min in either milk or dry conditions. Cell membrane integrity was determined by BCECF/AM dye inclusion. Plating efficiency was determined by measurement of cell attachment at 3 and 6 h. The clonogenic capacity of progenitor cells was estimated by limiting dilution and colony counts. For all assays teeth stored in milk at 4 degrees C showed the highest percentages of BCECF positive, attached cells with clonogenic capacity. Increased storage time (15-120 min) was associated with a 50% relative reduction of BCECF staining and a 5-fold relative reduction of cell attachment regardless of storage conditions. However, the clonogenic capacity of progenitor cells decreased 25-fold over the same duration of storage. These data demonstrate that in vitro assays of clonogenic capacity are much more sensitive to extra-oral storage time and storage conditions than dye inclusion or cell attachment. We suggest that in comparison with in vitro measures of cell membrane integrity, the clonogenic capacity of PL cells is more closely liked to tooth survival rate, probably reflecting the capacity of PL progenitor cells to recolonize the root surface after replantation.

Adolescent↗

The receptor tyrosine kinase QEK5 mRNA is expressed in a gradient within the neural retina and the tectum.

In the retinotectal system, positional information has long been postulated to take the form of molecular gradients within both the retina and the tectum. Recent reports have implicated Mek4, a member of the Eph (also named class V) family of tyrosine kinase receptors (RTKs), and two ligands, RAGS and ELF-1, in this process. Here, we report the cloning and distribution pattern of QEK5, another member of the Eph family of RTKs, isolated from a quail cDNA library. During retinal differentiation, QEK5 transcripts accumulate in a ventral to dorsal gradient within the retinal neuroepithelium, where its expression becomes restricted to the ganglion and bipolar cell layers. Within the tectum, QEK5 transcripts are detectable in a posterior to anterior gradient in the ventricular layer and newly formed superficial layers. The pattern of QEK5 expression in the retina and tectum is distinct from that of Mek4, suggesting that complex patterns of Eph RTKs and their ligands may play a role in cell-cell interactions involved in retinotectal projections and differentiation of the central nervous system.

Amino Acid Sequence↗

Transforming growth factor beta 1 preserves endothelial function after multiple brief coronary artery occlusions and reperfusion.

The objective of this investigation was to determine the effect of transforming growth factor beta 1 (TGF-beta 1) on endothelium-dependent relaxation in isolated epicardial coronary artery rings obtained from anesthetized dogs after multiple brief episodes of coronary artery occlusion and reperfusion in vivo. Dogs were subjected to four 5-minute periods of left anterior descending coronary artery occlusion interspersed with 5 minutes of reperfusion and followed by a final 1-hour period of reperfusion. Normal left circumflex coronary arteries were used as control samples. Repetitive ischemia and reperfusion significantly (p < 0.01) inhibited the relaxation response to acetylcholine in rings preconstricted with potassium. In an additional group of dogs subjected to the same protocol, 10 micrograms of human recombinant TGF-beta 1 was infused into the left anterior descending coronary artery distal to the site of occlusion via a diagonal branch at 0.3 ml/min immediately before and during the repetitive occlusions and reperfusions. TGF-beta 1 prevented impaired endothelium-dependent relaxation after multiple brief occlusions and reperfusions. These results demonstrate a protective role for TGF-beta 1 in the endothelial injury that occurs during repeated episodes of coronary artery occlusion and reperfusion.

Acetylcholine↗

Interpretation of random urinary catecholamines and their metabolites in neuroblastoma.

This study reports experience in the estimation of urinary catecholamines (uCATs) and their metabolites in the diagnosis and follow-up of neuroblastoma. Random urine samples were assayed for dopamine, noradrenaline and adrenaline, together with their metabolites 4-hydroxy 3-methoxymandelic acid (HMMA) and homovanillic acid (HVA), using HPLC with electrochemical detection. Twenty of 21 patients had elevation of one or more uCATs metabolites at diagnosis. Patients were monitored serially from diagnosis and, in those patients who had delayed resection of primary tumour (n = 13), particular attention was paid to levels at the pre-surgical evaluation as an indicator of persistence of viable disease at the time of surgery; dopamine proved to be the most accurate indicator of persistent disease at this time. Five of these patients developed recurrent disease, 4 of whom had elevation of two or more uCATs metabolites at the time of relapse. Several conclusions can be drawn from this study: (a) results for HMMA, HVA and dopamine in random urine samples will detect all but the most biochemically immature or inert tumours; (b) dopamine may be the most reliable indicator of persistent disease and (c) noradrenaline and adrenaline measurements were of little benefit. As results are expressed in relation to urinary creatinine, excretion of which may be affected by dietary protein and is therefore not constant, borderline results should be repeated.

Catecholamines↗

Cultured endothelial cells restore vasodilator responses to coronary arteries with impaired endothelial function and alter the response to a nitric oxide donor.

The objective of this investigation was to determine the effect of cultured human umbilical vein endothelial cells (HUVEC) on the vascular response to canine coronary arteries in which the endothelium had been either mechanically removed or injured by multiple brief episodes of occlusion and reperfusion in vivo. The endothelium-dependent vasodilator, A23187 (10(-6) mol/l) did not cause any significant relaxation in vessels from which the endothelium had been removed. However, following addition of cultured HUVEC to the tissue bath (75 x 10(3) cells/ml), A23187 produced a significant (p < 0.05) relaxation. This effect was abolished by inhibition of nitric oxide synthase with Nw-nitro-l-arginine methyl ester (L-NAME). Vascular relaxation caused by the nitric oxide donor SIN-1 was significantly (p < 0.05) enhanced when cultured HUVEC were added to vessels mechanically denuded of endothelium. Repetitive ischemia and reperfusion significantly inhibited the relaxant response to A23187. Addition of cultured HUVEC to the tissue bath partially restored the response to A23187. In contrast to the mechanically damaged vessels the relaxant response to SIN-1 was unaffected by cultured HUVEC in reperfusion-injured vessels. These results demonstrate that cultured endothelial cells partially restore endothelium-dependent vasodilation of vessels in which the endothelium is not functional following mechanical- or reperfusion-induced damage. The differential effect of endothelial cells on the response to SIN-1 suggests that mechanical and reperfusion injury alter the coronary vascular response to SIN-1 by different mechanisms.

Animals↗

Determinants of time lost from workplace injuries: the impact of the injury, the injured, the industry, the intervention and the insurer.

Data from the WorkCover Authority of New South Wales (NSW), Australia pertaining to all injured workers who had at least 1 week time lost from work due to a workplace injury or illness from the health, manufacturing and retail industries in the Newcastle and Hunter regions of New South Wales, Australia, between 1 July and 31 December 1992, were analysed via a series of multiple regression analyses, to determine the relative impacts of injury, worker and organizational factors on the amount of time lost from a workplace injury or illness. The results indicated that the injury variables accounted for 28% of the variance in amount of time lost, and worker variables contributed a further 34% bringing the total explained variance to 62%. Insurer type, employer size and referral to an accredited rehabilitation provider also contributed to the amount of time lost after controlling for both injury and worker characteristics. The roles of worker characteristics, insurer type and accredited rehabilitation providers in time lost need further investigation.

Absenteeism↗

Is there a role for dietary fish oil in the treatment of hypertension?

Hypertension and atherosclerosis are highly prevalent disorders which contribute substantially to the burden of premature morbidity and mortality at significant cost to the economy. Hypertension, abdominal obesity and risk factor clustering represent complex regulatory disorders which probably reflect an interaction of multiple genetic and environmental factors. Information has been summarised which indicates that fish oil, obtained either as a dietary supplement or by the consumption of more fish products, represents a relatively simple and comparatively inexpensive dietary intervention which may lower BP, especially in combination with a low salt diet, and favourably alter multiple risk factors in the cluster. This summary also indicates that multiple significant gaps in our knowledge about fish oil remain. Closing these gaps through further clinical and basic research may lead to greater acceptance and more appropriate therapeutic use of fish oil for health maintenance and disease prevention.

Animals↗

Limitations of color flow Doppler imaging in the quantification of valvular regurgitation: velocity of regurgitant jet, rather than volume, determines size of color Doppler image.

The objective of this study was to determine the validity of estimation of regurgitant volume by visual assessment of color flow Doppler display. An experimental apparatus was designed that is capable of ejecting precise volumes of echogenic material from one chamber to another under continuous color flow Doppler monitoring. The velocity of flow was altered independently by changing either the size of the orifice through which flow occurred or the ejection rate. In this manner the differential effects of volume and velocity on the color flow Doppler image could be examined. The maximum area encompassed by the color flow Doppler pattern for each ejection was planimetered by using commercially available on-line software. In addition the reviewer in each case applied a subjective grade to the appearance of the color flow jet (1+ to 4+). Comparison was then made of the color flow Doppler appearance of equal volumes flowing at different velocities and of different volumes flowing at different velocities. In the initial series a solution of agitated hetasarch was used. When equal volumes were imaged at different velocities the higher-velocity jet appeared larger, both subjectively (3+ vs 1+) and by measuring the area encompassed in the Doppler flow profile (40.3 +/- 1.8 vs 22.0 +/- 1.4 cm2, p = 0.0001). Furthermore, when different volumes were imaged at different velocities, the smaller volume (3 ml vs 6 ml) appeared larger when it was flowing at higher velocity (3+ vs 2+, 40.3 +/- 1.8 vs 32.4 +/- 1.3 cm2, p = 0.0006). These experiments were repeated with blood, confirming the results of the initial study.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗

Differential sensitivity of proximal and distal coronary arteries to a nitric oxide donor following reperfusion injury or inhibition of nitric oxide synthesis.

OBJECTIVE: The effect of the nitric oxide donor, SIN-1, in proximal and distal coronary arteries with normal endothelium was characterised before and after inhibition of NO synthesis with L-nitroarginine methyl ester (L-NAME). The effect of reperfusion injury in vivo in similar vessels on the response to SIN-1 was also assessed. METHODS: In vitro reactivity of preconstricted coronary arterial rings was studied in control dogs (group 1), and dogs in which the left circumflex coronary artery was subjected in vivo to four acute occlusions of 5 min duration, with three intervening reperfusion periods of 5 min and a final reperfusion period of 60 min (group 2). The effects of acetylcholine and SIN-1 on the tone of left circumflex and left anterior descending coronary vascular rings were examined before and after treatment with L-NAME. RESULTS: Proximal [1851 (SEM 82) microns] and distal [477(19) microns] vessels were studied. In control dogs (group 1) acetylcholine caused relaxation in proximal and distal coronary arteries (p > 0.05). No difference in responsiveness of left circumflex or left anterior descending coronary arteries was observed in the control group. In group 2 the response to acetylcholine was significantly (p < 0.05) attenuated in left circumflex coronary arteries exposed to ischaemia and reperfusion compared with left anterior descending control rings from the same heart. Proximal vessels in group 1 and group 2 showed greater sensitivity to the vasodilator effects of SIN-1 than distal vessels. Proximal left circumflex vessels exposed to ischaemia and reperfusion showed enhanced sensitivity to the relaxant effects of SIN-1 compared to control proximal vessels obtained from the same hearts. Reperfusion was not associated with any alteration in sensitivity of distal vessels to SIN-1. Similarly, inhibition of the synthesis of endothelium derived relaxing factor (EDRF) by L-NAME resulted in an enhanced response to SIN-1 in proximal vessels only. CONCLUSIONS: Endothelium dependent vasodilatation is attenuated by ischaemia and reperfusion in both proximal and distal coronary arteries of the size studied. The response to direct nitric oxide donation (bypassing vascular endothelial synthesis of EDRF) is inhibited by a basal endothelial process present in proximal coronary arteries only. This inhibition is abolished following reperfusion injury or inhibition of NO synthesis.

Animals↗

Method comparison.

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Data Interpretation, Statistical↗

A study of interferences in routine methods for creatinine measurement.

A survey was undertaken through the Irish External Quality Assessment Scheme to investigate the extent to which acetoacetate and bilirubin affect routine methods in current use for measurement of serum creatinine. Spiking a sample with 10 mmol/l acetoacetate caused errors ranging from -28% to +22%. The greatest errors were found with end-point Jaffé methods and kinetic Jaffé methods in which there was no time delay between final reagent addition and start of absorbance measurement. A sample with high bilirubin concentration gave apparent creatinine results ranging from zero to 280 mumol/l. Although these interferences are well documented in the literature, this knowledge seems to have had little effect on methods in actual use.

Acetoacetates↗

Effect of omega-3 fatty acids on the vascular response to angiotensin in normotensive men.

There is a widespread interest in fish oil as a dietary supplement and possible nonpharmacologic adjunct in the treatment of hypertension. The effect of dietary fish oil on blood pressure is controversial and the effect on systemic hemodynamics and regional vascular reactivity in humans is unknown. To address these questions, a double-blind, placebo-controlled, crossover study on the effect of dietary fish oil substitution was performed during a carefully controlled diet in 8 normotensive men. Systemic hemodynamics and the forearm vascular response to intrabrachial artery infusions of norepinephrine, phentolamine and angiotensin II were obtained. Compared with a safflower oil placebo, dietary fish oil had no effect on cardiac output (6.42 +/- 0.38 vs 6.87 +/- 0.28 liters/min, p = not significant) or 24-hour blood pressure (122/68 +/- 3/3 vs 122/68 +/- 3/2 mm Hg, p = not significant). The vascular response to norepinephrine and phentolamine was unchanged. Fish oil, however, significantly (p < 0.05) reduced forearm vascular resistance responses to angiotensin II. These changes were associated with a reduction in plasma triglycerides (64 +/- 9 vs 39 +/- 4 mg/dl, p = 0.02) and an increase in plasma eicosapentaenoic acid levels (0.51 +/- 0.25 vs 1.72 +/- 0.35 microM, p < 0.05). Substitution of a moderate dose of fish oil for fat in a "Western diet" selectively attenuates the vascular response to angiotensin independently of changes in alpha-adrenergic vasoconstriction or systemic hemodynamics.

Adult↗

Dietary fish oil and rheumatic diseases.

Dietary fish oil supplementation can induce several metabolic changes relevant to rheumatic diseases. Both experimental and clinical evidence show that dietary fish oil supplementation modulates inflammatory and immune responses. Many studies have shown beneficial, albeit modest, effects in the treatment of rheumatoid arthritis. Studies in murine models of systemic lupus erythematosus have been encouraging, but few studies have been performed to assess the effects of dietary fish oil in the human disease or in other systemic rheumatic diseases. Further study on the efficacy of dietary fish oil supplementation in the treatment of specific rheumatic diseases is warranted.

Arthritis, Rheumatoid↗

The paradoxical effects of dietary fish oil on blood pressure.

Dietary fish oil supplementation has received considerable interest as a non-pharmacological adjuvant in the treatment of several diseases, especially hypertension. However, epidemiological, clinical, and experimental evidence conflict. A hypothesis is proposed that fish oil, may have a variable effect on vascular reactivity and consequently, blood pressure. A mechanism is proposed and reasons for the variation in the literature suggested. On the basis of this analysis a potentially adverse effect of dietary fish oil on blood pressure in some individuals is suggested.

Animals↗

Reference values for urinary HMMA, HVA, noradrenaline, adrenaline, and dopamine excretion in children using random urine samples and HPLC with electrochemical detection.

Random urine samples were collected from 305 children aged from birth to 14 years and the values of hydroxymethoxymandelic acid, homovanillic acid, noradrenaline, adrenaline, and dopamine were measured by high-performance liquid chromatography with electrochemical detection. The results were reported relative to the urinary creatinine concentration and the values declined progressively with increasing age for each analyte with the exception of adrenaline. The results for each age group were not normally distributed and all values except outliers were retained in determining the upper reference limits.

Adolescent↗