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Biomedical subjects

G Mason

Publications and source records attributed to G Mason.

At least 19 recordsLinked to original sources
PubMed2006

Co-current and counter-current imbibition in independent tubes of non-axisymmetric geometry.

Experiments that illustrate and quantify the basics of co- and counter-current spontaneous imbibition have been conducted in a series of simple model pore systems. The fundamental pore geometry is a rod in an angled round-bottomed slot with the rod touching a capping glass plate. The capillaries thus formed by the surfaces of the slot, rod and plate do not have circular cross-sections but more complicated geometric structures with angular corners. The tubes formed at each side of the rod connect at both ends. A viscous, refined oil was applied from one end. For co-current experiments, the opposite end was left open to the atmosphere and oil imbibed into both tubes. For counter-current experiments the opposite end was sealed and connected to a sensitive pressure transducer. Oil imbibed into the smaller capillary and expelled air as a series of bubbles from the end of the larger capillary. Bubble snap-off was observed to be rate-dependent and occurred at a lower curvature than that of the cylindrical meniscus that just fits inside the tube. Only the corners of the larger capillary filled with oil during counter-current imbibition. Meniscus curvatures were calculated using the Mayer and Stowe-Princen method and were compared with actual values by measuring the capillary rise in the tubes; agreement was close. A simple model for co-current and counter-current imbibition has also been developed and the predictions compared with the experimental results. The model results were in agreement with the experiments. The experiments demonstrate that the capillary back pressure generated by the interfaces and bubbles in counter-current imbibition can slow the process significantly.

Journal Article↗
PubMed2006

Assessing the welfare of genetically altered mice.

In 2003, under the auspices of the main UK funders of biological and biomedical research, a working group was established with a remit to review potential welfare issues for genetically altered (GA) mice, to summarize current practice, and to recommend contemporary best practice for welfare assessments. The working group has produced a report which makes practical recommendations for GA mouse welfare assessment and dissemination of welfare information between establishments using a 'mouse passport'. The report can be found at www.nc3rs.org.uk/GAmice and www.lal.org.uk/gaa and includes templates for the recommended welfare assessment scheme and the mouse passport. An overview is provided below.

Animal Husbandry↗
PubMed2006

Amniocentesis results: investigation of anxiety. The ARIA trial.

OBJECTIVES: The Amniocentesis Results: Investigation of Anxiety (ARIA) trial tested two hypotheses: first, that giving amniocentesis results out on a fixed date alters maternal anxiety during the waiting period, compared with a policy of telling parents that the result will be issued 'when available' (i.e. a variable date), and secondly, that issuing early results from a rapid molecular test alters maternal anxiety during the waiting period, compared with not receiving any results prior to the karyotype. The effects of the two interventions on anxiety 1 month after receiving karyotype results were also examined. DESIGN: A multi-centre, randomised, controlled, open fixed sample, 2 x 2 factorial design trial, with equal randomisation. SETTING: Twelve hospitals in England offering amniocentesis as a diagnostic test for Down's syndrome. PARTICIPANTS: A total of 226 women who had had an amniocentesis were randomised between June 2002 and July 2004. Eight women with abnormal results or test failure were excluded post-randomisation. INTERVENTIONS: Issuing karyotype results on a prespecified fixed date, rather than issuing them as soon as they became available and issuing karyotype results alone, or subsequent to issuing results from a rapid molecular test for the most common chromosomal abnormalities. MAIN OUTCOME MEASURES: Average anxiety during the waiting period, calculated using daily scores from the short version of the Spielberger State-Trait Anxiety Inventory (STAI). Recalled anxiety, measured 1 month after receiving karyotype results, using a rating scale. Anxiety at the 1-month follow-up, measured using the short-form STAI. RESULTS: There was no evidence that giving out karyotype results on a fixed or on a variable date altered maternal anxiety during the waiting period. However, the analysis only had sufficient power to detect a moderate to large effect. Issuing early results from a partial, but rapid, test reduced maternal anxiety during the waiting period, compared with receiving only the full karyotype results. This was a moderate to large effect. In addition, group differences in recalled anxiety reflected fairly closely the differences in anxiety women had experienced while waiting for results. One month after receiving normal karyotype results, anxiety was low in all groups, but women who had been given rapid test results were more anxious than those who had not. This was a small to moderate effect. CONCLUSIONS: Since there are no clear advantages in anxiety terms of issuing karyotype results as soon as they become available, or on a fixed date, women could be given a choice between them. Rapid testing was a beneficial addition to karyotyping, at least in the short term. This does not necessarily imply that early results would be preferred to comprehensive ones if women had to choose between them. There should be further research, including more qualitative studies, into the causes, characteristics and consequences of anxiety associated with prenatal testing. The effects of different testing regimes on short- and long-term anxiety, on the preferences of women and on the relationship between anxiety and preference should be investigated. More research is needed on the ways in which information might be used to minimise anxiety in different testing regimes. Further research is also required into the policy implications of incorporating individual preferences for different testing regimes into prenatal testing programmes.

Adult↗
PubMed2005

Prenatal diagnosis of Herlitz junctional epidermolysis bullosa in nonidentical twins.

Advances in molecular diagnostics have led to the feasibility of DNA-based prenatal testing in families at risk for recurrence of severe forms of both dystrophic and junctional epidermolysis bullosa. In this report, we describe prenatal testing in a woman who previously had a child affected with Herlitz junctional epidermolysis bullosa. However, in her second pregnancy, she was found to have dichorionic diamniotic twins. DNA analysis of a pathogenic mutation and informative intragenic polymorphisms (LAMB3 gene) predicted one fetus to be affected and the other unaffected. Selective termination of the affected fetus was performed, and pregnancy with the unaffected fetus was continued, leading to full term delivery of a healthy girl with no skin blisters. This is the first reported case of DNA analysis in a twin pregnancy at risk of Herlitz junctional epidermolysis bullosa, with successful diagnosis and selective termination of one affected twin.

Adult↗
PubMed2005

Can rock climbing lead to Dupuytren's disease?

OBJECTIVES: To determine if rock climbing is a significant factor in the development of Dupuytren's disease in men, and, if so, what is the most likely related factor. METHODS: Questionnaires were distributed to all 1100 members of the Climbers' Club of Great Britain. These detailed basic information about the climber, the presence of Dupuytren's disease, and any known risk factors for its development. RESULTS: About half (51%) of the questionnaires were returned. The respondents were almost entirely male. It was revealed that 19.5% of male climbers had developed Dupuytren's disease. There was a significantly higher life time intensity of climbing activity in those with the disease. An earlier age of onset of the disease was found in climbers compared with the general population. CONCLUSIONS: This study further strengthens the hypothesis that repetitive trauma to the palmar fascia predisposes to the development of Dupuytren's disease in men.

Adult↗
PubMed2004

TYLCSV DNA, but not infectivity, can be transovarially inherited by the progeny of the whitefly vector Bemisia tabaci (Gennadius).

The transovarial transmission of two species of begomovirus, Tomato yellow leaf curl virus (TYLCV) and Tomato yellow leaf curl Sardinia virus (TYLCSV), through generations of Bemisia tabaci of the B and Q biotypes has been investigated. Different life stages of the progeny of viruliferous female whiteflies have been analysed by PCR detection of viral DNA and infectivity tests. Our results indicate that TYLCSV DNA can be detected in eggs and nymphs, and to a lesser extent adults, of the first-generation progeny. Infectivity tests using a large number of adult progeny of the first, second, and third generation indicate that even when viral DNA is inherited, infectivity is not. For TYLCV, neither viral DNA nor infectivity were associated with the progeny of viruliferous female whiteflies. Because the inherited viral DNA is unable to give rise to infections, the transovarial transmission of TYLCSV DNA appears to have no epidemiological relevance.

Animals↗
PubMed2004

Acute hand and wrist injuries in experienced rock climbers.

BACKGROUND: The sport of rock climbing has its own spectrum of injuries, almost half of which involve the wrist and hand. OBJECTIVE: To examine the incidence of acute wrist and hand injuries in 545 members of The Climbers' Club of Great Britain. METHOD: A total of 1100 questionnaires were sent to current members of The Climbers' Club of Great Britain for them to detail any hand and wrist injuries sustained to date. In decade years, the climbing grades and time spent climbing at each grade were determined. From these results a total and historic climbing intensity score for each climber could be calculated. RESULTS: Half of the questionnaires were returned complete. The respondents were almost entirely male. There were 235 wrist and hand injuries in 155 climbers (28%). The climbing intensity scores were significantly higher in the injury group than in those who had not suffered a wrist or hand injury (p<0.05). Finger tendon injuries were the most common injury, followed by abrasions/lacerations and fractures. DISCUSSION: The most common injuries found in rock climbing involve the wrist and hand. The predominant injury to the hand involves the finger tendons or pulleys. The greater the climbing intensity calculated over a climber's career, the greater the likelihood of sustaining these injuries.

Acute Disease↗
PubMed2003

S-adenosylmethionine (SAMe) in a feline acetaminophen model of oxidative injury.

S-adenosylmethionine (SAMe) is reported to have hepatoprotective and antioxidant functions. Acetaminophen (paracetamol) was used to induce oxidative damage in cats, and to then determine the effect of SAMe treatment on erythrocyte morphology, PCV, liver histopathology, thiobarbituate reacting substances (TBARS), reduced glutathione (GSH), and oxidised glutathione (GSSG). Cats receiving acetaminophen had a significant increase in methemoglobin and Heinz body production. A significant effect for the interaction of time and treatment was found for Heinz body production and changes in PCV. No significant changes were found in blood or hepatic TBARS. Blood GSH increased significantly in all cats, while the blood GSH:GSSG ratio tended to increase the most in cats given acetaminophen only. The hepatic GSH:GSSG ratio tended to increase in cats given SAMe and decrease in cats given acetaminophen, but this effect was not significant. SAMe protected erythrocytes from oxidative damage by limiting Heinz body formation and erythrocyte destruction and maybe useful in treating acetaminophen toxicity.

Acetaminophen↗
PubMed2001

MCV as a guide to phlebotomy therapy for hemochromatosis.

BACKGROUND: A multitude of recommendations exist for laboratory assays to monitor the pace and endpoints of phlebotomy therapy for hemochromatosis. All of these recommendations rely on an assessment of storage iron to guide treatment, and none have been prospectively evaluated. STUDY DESIGN AND METHODS: Nine consecutive patients underwent serial monitoring of Hb, MCV, transferrin saturation, and ferritin during weekly phlebotomy to deplete iron stores (induction therapy) and less frequent sessions to prevent iron reaccumulation (maintenance therapy). Changes in MCV and Hb were used to guide the pace of phlebotomy over a median of 7 years of follow-up. RESULTS: During induction therapy, the MCV increased transiently because of reticulocytosis and then stabilized for a prolonged period before decreasing more sharply, which reflected iron-limited erythropoiesis. Iron depletion was achieved after a median of 38 phlebotomies and removal of 9.0 g of iron. Maintenance phlebotomy was targeted to maintain the MCV at 5 to 10 percent below prephlebotomy values and the Hb at >13 g per dL. Transferrin saturation fluctuated considerably during treatment, but remained below 35 percent during MCV-guided maintenance therapy. Ferritin values were not useful guides to the pace of phlebotomy. The median maintenance therapy phlebotomy interval was 7.5 weeks (range, 6-16), which corresponded to an average daily iron removal of 35 to 67 microg per kg. Most patients showed evidence of iron reaccumulation at phlebotomy intervals of 8 weeks or more. CONCLUSION: The MCV is an inexpensive, precise, physiologic indicator of erythropoietic iron availability. When used in conjunction with the Hb, it is a clinically useful guide to the pace of phlebotomy therapy for hemochromatosis.

Adult↗
PubMed2000

Identification of syntaxin 1A as a novel binding protein for presenilin-1.

Mutations in the presenilin 1 gene have been shown to result in Alzheimer's disease. Presenilin 1 is a multi-transmembrane protein with a large hydrophilic loop near the C-terminus. This region is required for known functions of presenilin 1. We have constrained this loop within the active site of the bacterial protein, thioredoxin, to mimic its native conformational state. This hybrid protein was used as bait in a yeast two hybrid screen in an attempt to identify presenilin binding proteins. By this method syntaxin 1A, a synaptic plasma membrane protein, was identified as a novel binding protein for presenilin 1. In vitro experiments confirm the two-hybrid results suggesting that PS1 binds syntaxin under physiological conditions.

Alzheimer Disease↗
PubMed2000

The novel NK1 receptor antagonist MK-0869 (L-754,030) and its water soluble phosphoryl prodrug, L-758,298, inhibit acute and delayed cisplatin-induced emesis in ferrets.

The anti-emetic profile of the novel brain penetrant tachykinin NK1 receptor antagonist MK-0869 (L-754,030) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluor o)phenyl-4-(3-oxo-1,2,4-triazol-5-yl)methylmorpholine and its water soluble prodrug, L-758,298, has been examined against emesis induced by cisplatin in ferrets. In a 4 h observation period, MK-0869 and L-758,298 (3 mg/kg i.v. or p.o.) inhibited the emetic response to cisplatin (10 mg/kg i.v.). The anti-emetic protection afforded by MK-0869 (0.1 mg/kg i.v.) was enhanced by combined treatment with either dexamethasone (20 mg/kg i.v.) or the 5-HT3 receptor antagonist ondansetron (0.1 mg/kg i.v.). In a model of acute and delayed emesis, ferrets were dosed with cisplatin (5 mg/kg i.p.) and the retching and vomiting response recorded for 72 h. Pretreatment with MK-0869 (4-16 mg/kg p.o.) dose-dependently inhibited the emetic response to cisplatin. Once daily treatment with MK-0869 (2 and 4 mg/kg p.o.) completely prevented retching and vomiting in all ferrets tested. Further when daily dosing began at 24 h after cisplatin injection, when the acute phase of emesis had already become established, MK-0869 (4 mg/kg p.o. at 24 and 48 h after cisplatin) prevented retching and vomiting in three out of four ferrets. These data show that MK-0869 and its prodrug, L-758,298, have good activity against cisplatin-induced emesis in ferrets and provided a basis for the clinical testing of these agents for the treatment of emesis associated with cancer chemotherapy.

Acetals↗
PubMed2000

The subjective assessment of echogenic fetal bowel.

OBJECTIVES: To assess the subjective interpretation of the echogenicity of fetal bowel compared to bone from antenatal ultrasound images taken during examinations conducted between 17 and 22 weeks of gestation. METHODS: Eighty-seven women attending for their antenatal scan were selected in a random prospective manner over a 9-month period. Images of the fetal bowel were taken and evaluated by 10 sonographers, one consultant obstetrician and one consultant radiologist. Images from a further 13 fetuses, in which the subjective assessment of echogenic bowel was made, were also included. All ultrasound images were acquired on a dedicated ultrasound scanner, with a standard transducer, thermal paper printer and single operator using standardized equipment settings and reproducible image sections. Questionnaires with 100 sets of images of fetal bowel were distributed to the participants. Performance was assessed by means of percentage agreement and levels of chance corrected agreement (Kappa). RESULTS: The subjective assessment of fetal bowel echogenicity is very variable. Intra- and inter-observer variation discrepancies in the assessment of bowel echogenicity compared to bone were demonstrated between the sonographers. Good agreement was identified between the consultants with good to almost perfect intra-observer agreement. Overall, only moderate agreement was observed between the sonographers and the consultants. CONCLUSIONS: The lack of agreement demonstrated between sonographers when evaluating the echogenicity of fetal bowel should be addressed if this ultrasound marker is to be incorporated into routine fetal screening programs.

Adult↗
PubMed1999

Selective NMDA NR2B antagonists induce antinociception without motor dysfunction: correlation with restricted localisation of NR2B subunit in dorsal horn.

The present study investigated the regional distribution of the N-methyl-D-aspartate (NMDA) receptor containing the NR2B subunit protein in rat lumbar spinal cord and examined whether selective NR2B antagonists would exhibit antinociception with reduced side-effect liability than subtype non-selective NMDA antagonists and anticonvulsants. Immunocytochemical studies showed the NR2B subunit had a restricted distribution, with moderate labelling of fibres in laminas I and II of the dorsal horn suggesting a presynaptic location on primary afferent fibers and possible involvement in pain transmission. In the in vivo studies, the NMDA/glycine antagonists (MK-801, 0.02-1 mg/kg i.p., L-687,414 10-300 mg/kg i.p., and L-701,324 1-10 mg/kg i.p.) and the anticonvulsant, gabapentin (10-500 mg/kg p.o.), induced rotarod deficits at antinociceptive doses. In contrast, the selective NR2B antagonists, (+/-)-CP-101,606 (1-100 mg/kg p.o.) and (+/-)-Ro 25-6981 (3-100 mg/kg i.p.) showed a significant dose window. (+/-)-CP-101,606 caused no motor impairment or stimulation in rats at doses up to 100 mg/kg p.o., which is far in excess of those inhibiting allodynia in neuropathic rats (ID50 4.1 mg/kg, p.o.). (+/-)-Ro 25-6981 also showed a significant separation (ID50 allodynia 3.8 mg/kg, i.p.), however, some disruption of rotarod performance was observed at 100 mg/kg. The anticonvulsant lamotrigine (3-500 mg/kg p.o.) also showed a good dose window. These findings demonstrate that NR2B antagonists may have clinical utility for the treatment of neuropathic and other pain conditions in man with a reduced side-effect profile than existing NMDA antagonists.

Acetates↗
PubMed1999

Analysis of the neurotrophic effects of GPI-1046 on neuron survival and regeneration in culture and in vivo.

The putative neurotrophic effects of the immunophilin ligand GPI-1046 were evaluated in established experimental systems of neuron survival and axon growth in vitro and in vivo. GPI-1046 marginally increased neurite outgrowth of chick dorsal root ganglia in culture under conditions where a very robust effect of nerve growth factor was seen. GPI-1046 failed to protect dopaminergic neurons from 1-methyl-4-phenylpyridinium in culture or to protect cultured cortical neurons from experimentally induced apoptosis in vitro. In adult rats in vivo, daily administration of GPI-1046 (10 mg/kg, s.c.) for three days enhanced the maximal regeneration distance of both motor and large myelinated sensory axons measured using an electrophysiological assay. However, detailed morphometric analysis of these animals failed to provide evidence for an increase in axon numbers in GPI-1046-treated animals. The ability of GPI-1046 to promote the recovery of dopaminergic function following unilateral 6-hydroxydopamine lesions of the substantia nigra was also tested in rats. In the first study, the duration of amphetamine (3 mg/kg, s.c.)-induced circling, but not the maximal number of rotations, was significantly reduced in animals treated with GPI-1046 for five days (10 mg/kg/day). In a second study, testing the effects of delayed GPI-1046 administration, chronic treatment with GPI-1046 (10 mg/kg/day) for two weeks, beginning one month after surgery, did not alter circling responses. Morphometric analysis failed to reveal any changes in either the density of tyrosine hyroxylase-positive fibres in dopaminergic target areas or in cell numbers in the substantia nigra in both experiments. Thus, while GPI-1046 produced marginal effects on neurite outgrowth in dorsal root ganglia cultures and on functional paramaters of nerve regeneration in vivo, we failed to obtain evidence in support of the notion of a general neuroprotective effect of the compound or for an effect on morphologic nerve regeneration in vivo.

1-Methyl-4-phenylpyridinium↗
PubMed1999

Possible antimigraine mechanisms of action of the 5HT1F receptor agonist LY334370.

This study investigated whether the selective 5HT1F receptor agonist LY334370 has other possible antimigraine mechanisms in addition to the proposed inhibition of dural plasma extravasation. LY334370 (up to 10(-5) M) had no vasoconstrictor effects on human cerebral arteries in vitro. It had no effect (up to 10 mg kg-1, i.v.) on neurogenic vasodilation of dural blood vessels produced by electrical stimulation of the dura mater in anesthetized rats. Nor had it any effect (at 3 mg kg-1, i.v.) on the hyperalgesia produced by injection of carrageenan into the paw of conscious rats or on nociceptive reflex responses in the spinalized, decerebrate rabbit (up to 3 mg kg-1, i.v.), indicating that it has no general analgesic properties. However, it significantly inhibited activation of second-order neurons in the trigeminal nucleus caudalis produced by electrical stimulation of the dura mater in anesthetised rats at 3 mg kg-1, i.v. These results provide evidence to suggest that LY334370 has a central mechanism of action in blocking the transmission of nociceptive impulses within the trigeminal nucleus caudalis and that this may represent a mechanism through which it has its antimigraine effect.

Animals↗
PubMed1999

Psychobiological markers of stress in pregnancy: 6-sulfatoxymelatonin--a longitudinal study.

Maternal stress, physical and psychological, has been associated with adverse pregnancy outcome. The pineal gland is a physiological transducer that reflects adrenergic input. In a recent pilot study, we found urinary 6-sulfatoxymelatonin, the melatonin metabolite, to be elevated after a women spent a day at work compared to levels after a day off work, a leisure day. To evaluate the value of melatonin as a marker of stress, we evaluate melatonin metabolite levels in 121 women, along with perceived anxiety levels and urinary cortisol. Urinary cortisol and maternal anxiety levels each were significantly higher after a work day compared to a leisure day p = .03 and p = .001, respectively. 6-Sulfatoxymelatonin was not significantly different between work and leisure. Changes in cortisol levels were correlated with changes in melatonin metabolite levels (r = .62, p = .001). There was no correlation between changes in anxiety between work and leisure and changes in 6-sulfastoxymelatonin. We found no correlation with 28 week 6-sulfatoxymelatonin or 28-week cortisol and birth weight or gestational age at delivery. Results of this study suggest that melatonin secretion may not be a valuable marker for stress in pregnancy.

Adult↗