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Biomedical subjects

P Dolan

Publications and source records attributed to P Dolan.

At least 19 recordsLinked to original sources

Successful reversal of primary graft non-function in a liver transplant patient treated with prostaglandin E1.

A 63 year old woman with liver failure received a transplant from a 21 year old male diagnosed as brain dead following a motor accident. After the operation, bile production was virtually absent and aspartate transaminase (AST) values rose dramatically 40 h postoperatively. Primary non-function of the graft was diagnosed, and the patient put on an urgent list for retransplantation. At the same time a continuous intravenous infusion of PGE1 was administered. Aspartate transaminase levels decreased within 9 h and reached normal levels by the sixth postoperative day, when bile production began to increase. Liver function subsequently returned to normal.

Alprostadil

A technique for quantifying the bending moment acting on the lumbar spine in vivo.

The bending properties of cadaveric lumbar spines were measured and used to convert in vivo measurements of lumbar flexion into bending moments ('stresses'). Forty-two lumbar motion segments were subjected to complex physiological loading and graphs were obtained of bending moment vs flexion angle. Variability was reduced by expressing both variables as a percentage of their values at the elastic limit. Data were averaged for each lumbar level, and a composite bending curve was compiled for the lumbar spine, L1-S1. A linear relationship was established between lumbar flexion measured in vitro and in vivo. This enabled values of 'per cent lumbar flexion' measured in vivo to be converted into 'per cent maximum bending moment' with a maximum likely error of about +/- 8%, which is equivalent to about +/- 5 Nm at L5-S1 for an average person. The technique was applied to 28 subjects, using dynamic measurements of lumbar flexion obtained with the '3-Space Isotrack' system. The bending moment at L5-S1 was 12 Nm on average when picking a pen up off the floor. Highly significant increases in bending moment were observed when heavier and bulkier objects were lifted.

Adult

The in vivo and in vitro transmission ratio distortion of one complete and two partial t haplotypes in mice.

The effects of different types of insemination (normal and delayed matings and in vitro fertilization) on the transmission ratio distortion (TRD) of three t haplotypes were determined. The tw73 haplotype which contains all of the loci known to affect TRD is transmitted at equivalent frequencies in normal matings and in in vitro fertilizations (0.84 and 0.85, respectively) but at a significantly lower frequency (0.62) in delayed matings. The distal partial th18 haplotype is transmitted at equivalent frequencies in all types of insemination (0.66 to 0.70) while the proximal partial tw18 haplotype is transmitted in Mendelian frequencies in normal matings and in in vitro inseminations but at a significantly lower frequency in delayed matings. The results are discussed with reference to the current genetic model for transmission ratio distortion.

Animals

Diurnal changes in spinal mechanics and their clinical significance.

Diurnal changes in the loads acting on the spine affect the water content and height of the intervertebral discs. We have reviewed the effects of these changes on spinal mechanics, and their possible clinical significance. Cadaveric lumbar spines subjected to periods of creep loading show a disc height change similar to the physiological change. As a result intervertebral discs bulge more, become stiffer in compression and more flexible in bending. Disc tissue becomes more elastic as its water content falls, and its affinity for water increases. Disc prolapse becomes more difficult. The neural arch and associated ligaments resist an increasing proportion of the compressive and bending stresses acting on the spine. Observations on living people show that these changes are not fully compensated for by modified muscle activity. We conclude that different spinal structures are more heavily loaded at different times of the day. Therefore, the time of onset of symptoms and signs, and any diurnal variation in their severity, may help us understand more about the pathophysiology of low back pain and sciatica.

Back Pain

Commonly adopted postures and their effect on the lumbar spine.

The activity of the erector spinae muscles and the changes in lumbar curvature were measured in 11 subjects in a range of commonly adopted postures to see if there were any consistent trends. Surface electrodes were used to measure back muscle activity and lumbar curvature was measured using electronic inclinometers. The results showed that many commonly adopted postures reduced the lumbar lordosis when compared with erect standing or sitting, even at the expense of increasing the back muscle activity.

Adult

The lumbar spine in backward bending.

Cadaveric lumbar motion segments were loaded to simulate backward bending (extension) movements of the lumbar spine. The motion segments' resistance was measured initially, and after the spinous processes and apophyseal joints had been cut through in turn. Compression tests were then performed on the discs while they were wedged in full extension. The results showed that extension is resisted mainly by the disc and spinous processes, and that, in hyperextension, damage usually occurs first in the spinous processes (or the soft tissue squashed between them). However, if the spinous processes are particularly widely spaced, then the apophyseal joints can become damaged first. The protection offered the disc by the neural arch is greater in young people, and after the disc height has been reduced by creep loading. The disc can be damaged in hyperextension if the spine is subjected to high compressive forces at the same time. A sudden application of compressive force can cause an anterior disc prolapse, while a cyclic (fatigue) compressive force can increase the posterior bulging of the lamellas in the posterior annulus.

Humans

Human muscle function following prolonged eccentric exercise.

4 subjects performed repeated eccentric contractions with leg extensors during prolonged downhill walking (-25% gradient) at 6.44 km.h-1 until collapse due to muscle weakness (range of exercise duration 29 to 40 min). During the exercise oxygen uptake rose progressively from approximately 45% of the previously determined VO2max at 10 min to approximately 65% at the end of the exercise. Following the exercise there was an immediate, significant, and sustained reduction in maximal voluntary isometric contraction, and short term (anaerobic) power output measured concentrically on an isokinetic ergometer. These reductions in muscle function persisted for 96 hours post exercise, and were reflected by significant reductions in the tension generated at low frequency (20 Hz) relative to higher frequency (50 Hz) percutaneous stimulation of the quadriceps. All four subjects showed an increase in plasma levels of creatine kinase post eccentric exercise. Performing concentric contractions by walking uphill for one hour at a significantly greater metabolic cost failed to induce comparable reductions in muscle function. These results provide evidence for the consequences of prolonged eccentric work upon dynamic function which complements earlier reports of structural, enzymatic, and static function changes.

Adult

Diurnal variations in the stresses on the lumbar spine.

Two complementary experiments were performed, the first on living people and the second on cadaveric spines. In the first experiment, electronic inclinometers were used to measure the range of lumbar flexion of 21 volunteers in the early morning and in the afternoon. The results showed that the range of movement increased by 5 degrees during the day. In the second experiment, cadaveric lumbar motion segments were creep loaded to simulate a day's activity and their bending properties were measured before and after creep. The results showed that creep loading reduces the spine's resistance to bending (the effect being particularly marked in the disc) and increases the range of lumbar flexion by 12.5 degrees. The results of the two experiments were combined to show that in life, forward bending movements subject the lumbar spine to higher bending stresses in the early morning compared with later in the day. The increase is about 300% for the discs and 80% for the ligaments of the neural arch. It is concluded that lumbar discs and ligaments are at greater risk of injury in the early morning.

Adolescent

Effect of prior exercise on maximal short-term power output in humans.

The effect of prior exercise (PE) on subsequent maximal short-term power output (STPO) was examined during cycling exercise on an isokinetic ergometer. In the first series of experiments the duration of PE at a power output equivalent to 98% maximum O2 uptake (VO2max) was varied between 0.5 and 6 min before measurement of maximal STPO. As PE duration increased subsequent STPO fell to approximately 70% of control values after 3-6 min. In series ii the effect of varying the intensity of PE of fixed 6-min duration was studied in five subjects. After PE less than 60% VO2max there was an increase of 12% in STPO, but after greater than 60% VO2max there was a progressive fall in STPO as PE intensity increased, indicating a reduction of approximately 35% at 100% VO2max compared with control values. In series iii we examined the effect on STPO of allowing a recovery period after a fixed intensity (mean = 87% VO2max) of 6 min PE before measurement of STPO. This indicated a rapid recovery of dynamic function with a half time of approximately 32 s, which is similar to the kinetics of PC resynthesis and taken with the other findings suggests the dominant role that PC exerts on the STPO under these conditions.

Adult

The short-term effects of chymopapain on intervertebral discs.

Cadaveric lumbar discs were injected with chymopapain and subjected to a series of mechanical tests over a period of up to 19 hours. Discs from the same spine injected with saline were used as controls. The results showed that chymopapain had no measurable effect on the mechanical properties of the disc apart from the increased height and stiffening caused by fluid injection. Another series of tests on isolated pieces of disc material showed that chymopapain could reduce the size of prolapsed nuclear material by 24% in one hour and by 80% in 48 hours. It is concluded that, in the short-term, chymopapain has a negligible effect on the mechanics of a disc but it can reduce the size of any prolapsed nuclear material with which it comes in contact.

Adult

Biochemical effects of dithiolthiones.

Administration of dithiolthiones to mice in single intragastric doses (2-4 mmol/kg body weight) or in the diet (0.5% for 14 days), and to rats in the diet (0.1% for 14 days) was found to increase glutathione levels and the activities of a number of enzymes in various tissues including the liver and lung. The enzymes affected were glutathione transferases (with chlorodinitrobenzene or dichloronitrobenzene), quinone and glutathione reductase, and glucose-6-phosphate and 6-phosphogluconate dehydrogenase, all of which are involved directly or indirectly in the detoxication of xenobiotics, including carcinogens. The dithiolthiones tested in mice were oltipraz, ADT, 116L and 129L, and in rats, oltipraz. Intragastric administration of dithiolthiones (oltipraz, ADT or 116L; two doses each of 1 g/kg body weight) did not increase glutathione levels or enzyme activities in murine mammary adenocarcinoma transplants. Increases in glutathione levels and enzyme activities similar to those found with dithiolthiones were observed when a semi-synthetic diet containing 10-40% lyophilized cabbage was fed to mice for 30 days. Dithiolthiones that are present in cabbage may play a role in the protective actions of diets high in vegetables against the toxic actions of xenobiotics. The biochemical effects of dithiolthiones reported here may account for the protective actions of these compounds.

Animal Feed

1,2-Dithiol-3-thione analogs: effects on NAD(P)H:quinone reductase and glutathione levels in murine hepatoma cells.

The 1,2-dithiol-3-thiones are a class of five-membered cyclic sulfur compounds which have chemotherapeutic and chemoprotective properties. The parent 1,2-dithiol-3-thione nucleus and a series of six substituted analogs all induced NAD(P)H: quinone reductase (EC 1.6.99.2) activity and elevated glutathione levels in Hepa 1c1c7 murine hepatoma cells in culture thereby enhancing detoxification potential. These analogs included monosubstituted derivatives with phenyl, p-methoxyphenyl or 2-pyrazinyl groups at C-4 or C-5, and disubstituted compounds bearing phenyl or 2-pyrazinyl moieties at C-5 and an additional methyl group at C-4. This system can be used as an in vitro model for the study of the specificity and mechanism of action of the 1,2-dithiol-3-thiones as already demonstrated for several other classes of chemoprotective agents. The 1,2-dithiol-3-thiones also elevated quinone reductase and glutathione levels in the Hepa 1c1c7 cell mutants (BPrc1 and TAOBPrc1) that are defective in aryl hydrocarbon receptor functions. We conclude that the 1,2-dithiol-3-thiones are largely concerned with the stimulation of metabolic inactivation of electrophiles.

Animals

The stages of disc degeneration as revealed by discograms.

One hundred and thirty-nine discs from cadaveric lumbar spines were injected with a mixture of radio-opaque fluid and dye. Discograms were taken and the discs were then sectioned in the sagittal plane. Examination of the sections revealed that injected fluid did not at first mix with the disc matrix but pushed it aside to form pools of injected fluid. The location of these pools, and hence the appearance of a discogram, depended on the stage of degeneration of the disc. It is concluded that useful clinical information can be obtained from discograms.

Adolescent