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Biomedical subjects

G Burton

Publications and source records attributed to G Burton.

At least 55 records · Page 3Linked to original sources
PubMed1997

Do postvaccinal sarcomas occur in Australian cats?

A soft tissue sarcoma occurred in the interscapular area of a cat, 1 to 7 months after vaccination at that site. The vaccine contained inactivated feline panleucopaenia virus combined with modified live feline herpesvirus and calicivirus. The tumour showed histological features of both fibrosarcoma and malignant fibrous histiocytoma. The tumour was observed to evolve from the site of a presumed postvaccinal granuloma. Local recurrence 6 weeks post excision necessitated more radical resection. Euthanasia was performed 2 years later when pleural effusion developed. The cause of effusion was not determined. There was no palpable evidence of local tumour regrowth at the time of euthanasia. A causal relationship between vaccination and sarcoma formation is considered based on the temporal association between the two events, the anatomical location of the tumour and histopathology consistent with postvaccinal sarcomas reported overseas. Six other vaccine site fibrosarcomas, potentially vaccine associated using the above criteria, are summarised.

Animals↗
PubMed1997

21-Hydroxy-6,19-oxidoprogesterone: a novel synthetic steroid with specific antiglucocorticoid properties in the rat.

In the rat, the conformationally highly bent steroid 21-hydroxy-6, 19-oxidoprogesterone efficiently displaces [3H]corticosterone from thymus-glucocorticoid receptors and blocks type II receptors in kidney cytosols but competes with neither [3H]aldosterone for kidney-mineralocorticoid receptors nor [3H]progesterone for uterus-progesterone receptors. It evokes Na+ retention only at very high doses (approximately 100 microg/100 g of rat weight) and is unable to induce tyrosine aminotransferase or to increase glycogen deposits in rat liver. When coincubated with corticosterone or dexamethasone, 2.5 microM 21OH-6OP inhibits 80% of tyrosine aminotransferase induction. It may therefore be used experimentally as an antiglucocorticoid virtually lacking mineralocorticoid or glucocorticoid properties as well as affinity for mineralocorticoid or progesterone receptors.

Aldosterone↗
PubMed1996

Synthesis of oxido-bridged analogs of 18-hydroxyprogesterone.

18-Hydroxy-6,19-oxidoprogesterone and 18-hydroxy-11, 19-oxidoprogesterone were synthesized from readily available materials. The functionalization of C-18 was accomplished with phenyliodosodiacetate/iodine, whereas that of C-19 was carried out with the mercuric oxide/iodine system, both under irradiation with visible light. For 18-hydroxy-11,19-oxidoprogesterone, C-19 was functionalized before C-18, whereas the reverse order had to be used for the 6,19-oxido derivative.

Hydroxyprogesterones↗
PubMed1996

Selective perception by dynamic touch.

Perceiving the length of a rod by dynamic touch is tied to the inertia tensor Iij, a quantification of its resistance to rotational acceleration. Perception of the portion extending in front of the grasp has previously been ascribed to decomposing one component of Iij by attention. The tensorial nature of dynamic touch suggests that this ability must be anchored wholly in the tensor. Three experiments show that perceived partial length is a function of two components of the tensor, one tied primarily to magnitude and the other tied primarily to direction, whereas perceived whole length is a function of a magnitude component alone. Dynamic touch is characterized in terms of a haptic perceptual instrument that softly assembles to exploit Iij differently depending on the intention, producing 1:1 maps that are appropriately scaled for each intention.

Adult↗
PubMed1996

Novel C-2 substituted carbapenem derivatives. Part I. Synthesis and biological activity of non-aromatic heterocyclic derivatives.

A new series of carbapenems, having a saturated or partially unsaturated heterocycle at C-2, has been synthesised. The in vitro antibacterial activity of these compounds and their stability to human dehydropeptidase-1 (DHP-1) are described. The stereochemistry of the C-2 side-chain and the presence of a double bond in the heterocycle were shown to have significant effects on the stabilities of the compounds to DHP-1.

Bacteria↗
PubMed1996

Novel C-2 substituted carbapenem derivatives. Part II. Synthesis and structure-activity relationships of isoxazolin-2-yl, isoxazolidin-2-yl and 2-pyrazolin-2-yl carbapenems generated using 1,3-dipolar cycloaddition chemistry.

A series of carbapenems containing novel C-2 semisaturated heterocyclic substituents were synthesised by 1,3 dipolar cycloaddition reactions of nitrile oxides, nitrile imines and a nitrone to 2-vinylcarbapenem. The isoxazoline and isoxazolidine compounds showed potent antibacterial activity but moderate stability to human dehydropeptidase 1 (DHP-1). Stability to DHP-1 was improved by methyl substitution in the isoxazoline ring, but at the expense of antibacterial activity. The pyrazolines exhibited excellent stability to DHP-1, but reduced potency against Gram-negative organisms.

Carbapenems↗
PubMed1995

Synthesis of 21-hydroxy-11,19-oxidopregn-4-ene-3,20-dione and 21-hydroxy-6,19-oxidopregn-4-ene-3,20-dione.

The 21-hydroxy analogues of 11,19-oxidoprogesterone and 6,19-oxidoprogesterone have been synthesized from readily available materials. Hydroxylation at C-21 was effected with iodosobenzene (from phenyliodosodiacetate and methanolic potassium hydroxide) on a 20-ketopregnane. For the 11,19-oxido derivative, the hydroxylation was carried out on a precursor containing the oxido-bridge. This approach was not adequate for the 6,19-oxido steroid due to the very low yields encountered; hence in the latter case the order of introduction of the C-21 functionality and the oxido-bridge was reversed.

Acetylation↗
PubMed1995

Biokinetics in humans of RRR-alpha-tocopherol: the free phenol, acetate ester, and succinate ester forms of vitamin E.

The bioavailability of RRR-alpha-tocopherol from the oral administration of RRR-alpha-tocopherol itself and its acetate and succinate esters was determined in healthy human subjects. Venous blood samples were withdrawn periodically over a 51-h period following oral administration of a gelatin capsule containing an equimolar mixture of RRR-alpha-tocopherol and RRR-alpha-tocopheryl acetate. In a second study, subjects received a capsule containing an equimolar mixture of RRR-alpha-tocopheryl acetate and RRR-alpha-tocopheryl succinate. In Study 1, RRR-alpha-tocopherol was absorbed at similar rates from both the free phenol, and the acetate ester and maximum plasma levels occurred at 12 h in most subjects. The extent of absorption of RRR-alpha-tocopherol varied considerably between subjects in absolute terms, but the relative absorption from the two forms was remarkably consistent, and a ratio of 1.0 was found for parameters of relative bioavailability in plasma. The concentration of RRR-alpha-tocopherol from each form was maximal at approximately 27 h in red blood cells and, as seen with the plasma data, there was a large interindividual variability. In Study 2, there was no significant difference in the extent of absorption of RRR-alpha-tocopherol from the acetate ester and the succinate ester, although there was an apparently higher initial rate of absorption from the acetate ester.

Administration, Oral↗
PubMed1995

Human chorionic gonadotrophin release and tissue viability in placental organ culture.

The use of human chorionic gonadotrophin (HCG) secretion as a measure of viability during the organ culture of human first trimester placental tissue has become a popular practice. It has been suggested that if cultured tissue is releasing large amounts of this protein hormone, there is a high level of viability. We have found, however, that the cytosolic enzyme L-lactate dehydrogenase is released into the culture supernatant in a similar daily pattern as HCG, suggesting that tissue disruption may be occurring, resulting in some of the observed hormone release. In addition, we have shown that the uptake of the fluorescent dye dansyl-L-lysine into the syncytium increases significantly from day 0 to day 4, suggesting a loss of syncytial membrane integrity. Electron micrographs show further evidence of the syncytial degeneration at the ultrastructural level, displaying extensive vacuolation and poor microvillous cover. In contrast to the degenerated state of the syncytiotrophoblast, a high level of bromodeoxyuridine incorporation is observed for cytotrophoblasts and, in particular, stromal cells up to 5 days in culture. Overall, the results suggest that the use of HCG release as a determinant of tissue viability in placental organ culture should be treated with a degree of caution.

Bromodeoxyuridine↗
PubMed1995

Modulation of ATP production by oxygen in obstructive lung disease as assessed by 31P-MRS.

Inadequate O2 supply may impair intramuscular oxidative metabolism and O2 availability may modulate ATP production within exercising muscle. Therefore, we studied ATP flux from anaerobic glycolysis, the creatine kinase reaction, and oxidative phosphorylation using 31P-magnetic resonance spectroscopy kinetic data collected during exercise. We examined six chronic obstructive pulmonary disease (COPD) patients with severe hypoxemia (group 1), seven COPD patients with mild hypoxemia (group 2), and seven healthy control subjects. Exercise (90-s isometric contraction of the gastrocnemius-soleus muscle group, 40% of max) was performed on room air for all subjects; for COPD patients, it was repeated during supplemental O2 at identical power outputs, with 60-min rest between the two sets. In group 1 (air vs. O2), oxidative phosphorylation ATP production was lower (P < 0.05), anaerobic glycolysis ATP production was higher (P < 0.05), and anaerobic glycolysis plus creatine kinase ATP production tended to be higher (P = 0.06). In group 2, no differences were observed across conditions. Assuming that mitochondrial size, density, function, and redox state were not affected by acute changes in the inspired O2 fraction, reduced O2 availability is the remaining factor that could have limited oxidative ATP production during hypoxemia. In conclusion, in severely hypoxemic COPD patients, O2 availability apparently limits intramuscular oxidative metabolism because acute hypoxemia increases anaerobic and decreases aerobic ATP production.

Adenosine Diphosphate↗
PubMed1995

Sodium-retaining activity of some natural and synthetic 21-deoxysteroids.

The effect of progesterone and six other C21-deoxysteroids on renal sodium retention by male adrenalectomized rats was compared with the effect exerted by the natural corticoids aldosterone, 11-deoxycorticosterone, and corticosterone. Steroids were active in the following order: aldosterone > 11,19-oxidoprogesterone > 5 alpha H-3,20-pregnanedione > or = 5 beta H-3,20-pregnanedione > progesterone = 11-ketoprogesterone > 6,19-oxidoprogesterone = 11-keto-6,19-oxidoprogesterone > or = corticosterone. All C21-deoxysteroids, except 11,19-oxidoprogesterone, exhibited parabolic log dose-response functions, indicating an effect that opposes renal sodium retention at high doses. 11,19-Oxidoprogesterone and the natural corticoids exhibited normal, exponential, log dose-response curves. Diverse geometric parameters related to molecular planarity were calculated and their correlation with biopharmacological properties was attempted. The best linear regression was obtained for correlation of the concavity of log dose-response parabolas (second-order coefficients) of C21-deoxysteroids with the C3 = O/ring D angle of these molecules. A good linear regression could also be obtained for correlation of the affinity of C21-deoxysteroids, except 11,19-oxidoprogesterone, for purified type I mineralocorticoid receptors with those angles. The latter correlation deteriorated upon incorporation of the affinity data for the three natural corticoids, due to similar affinities of these hormones for type I mineralocorticoid receptors, but could be restored when the binding data for the unpurified, corticosterone-binding globulin-containing stage of the receptors were considered. In vivo binding data followed the same trend as that for unpurified receptors.

Adrenal Glands↗
PubMed1994

Crossing without vision of path gaps.

Two experiments considered the behavior of subjects who cross gaps in a pathway without benefit of vision. The first experiment contrasted visually and nonvisually guided locomotion, finding a significantly greater number of refusals under nonvisual guidance but no loss of appropriate modulation of step components to the salient dimensions of the actor and layout. Different components of crossing were modified under guidance of different sensory systems; the lengths of the crossing and support spans were primarily altered under nonvisual guidance, and the distance of the support foot to the near edge of the gap was the component of preference under visual guidance. In the second experiment, subjects crossed nonvisually, using probes that varied in length and moment of inertia. The adaptability of the step components to actor and layout dimensions was unchanged, but there was no effect of these mechanical manipulations on the components of crossing identified in Experiment 1.

Journal Article↗
PubMed1994

Efficacy of oral ondansetron, a selective antagonist of 5-HT3 receptors, in the treatment of nausea and vomiting associated with cyclophosphamide-based chemotherapies. Ondansetron Study Group.

We evaluated the efficacy and safety of oral ondansetron, a selective antagonist of 5-HT3 receptors, for the treatment of nausea and vomiting associated with cyclophosphamide-based chemotherapy (> 500 mg/m2). In this trial 324 chemotherapy-naive cancer patients, mostly females with breast cancer, were randomized to receive either placebo or ondansetron 1 mg, 4 mg, or 8 mg three times per day for 3 days. There were no differences in the doses of cyclophosphamide, doxorubicin, and methotrexate between the study groups. All ondansetron dose groups were superior to the placebo control group (p < .001) for all measured efficacy parameters (complete response, number of emetic episodes, therapeutic failures, need of rescue antiemetics). No emetic episodes were reported by 9 (12%), 29 (37%), 48 (64%), and 47 (66%) of the placebo patients and the 1-mg, 4-mg, and 8-mg dose of ondansetron patients, respectively. Nausea was reduced and food intake was improved for all the ondansetron groups. A more severe emetic response was observed in patients receiving cyclophosphamide and doxorubicin combination chemotherapy. In this subgroup of patients, 66%, 38%, 25%, and 16% of the placebo group and 1-mg, 4-mg, and 8-mg ondansetron patients, respectively, required rescue antiemetics. No significant toxic effects were observed in this study. A higher incidence of headaches and gastrointestinal complaints (constipation, abdominal pain) were observed in the three ondansetron groups. In conclusion, oral ondansetron is an effective and well-tolerated antiemetic treatment in the management of cancer patients receiving ambulatory cyclophosphamide-based chemotherapy. These results support the view that serotonin and 5-HT3 receptors play an important role in cyclophosphamide-induced nausea and vomiting.

Administration, Oral↗
PubMed1993

Age, pregnancy and miscarriage: uterine versus ovarian factors.

This study was performed to evaluate the relative contribution of oocyte and uterine factors to the age-related reduction in fecundity. The pregnancy and miscarriage rates in women receiving donated oocytes were compared to those in women using their own oocytes in in-vitro fertilization (IVF) and gamete intra-Fallopian transfer (GIFT) procedures. Oocyte donation with embryo transfer was performed on 241 women in 371 cycles; 116 of these women became pregnant (48% per patient and 31.5% per cycle) of whom 40 (35%) miscarried, giving a live birth rate of 20.5%. Assisted conception, in the form of IVF/GIFT procedures, was performed on 1331 women using their own oocytes in 2194 cycles; 627 of these women became pregnant (47% per patient and 28.7% per cycle), of whom 228 (36%) miscarried, giving a live birth rate of 18.2%. Neither the age of the donor nor the age of the recipient was related to pregnancy rate. The age of the donor, however, was directly related to the miscarriage rate. On the other hand, the age of patients undergoing IVF/GIFT was inversely related to the pregnancy rate and directly related to the miscarriage rate. In women of 40 years or over, the overall pregnancy and live birth rates were significantly higher and the miscarriage rate was significantly lower in the group receiving donated oocytes compared to the group using their own oocytes. In summary, we suggest that the age-related decline in fecundity is associated with the age of the oocytes rather than the age of the uterus.

Abortion, Spontaneous↗
PubMed1993

Prevalence and significance of urethral instability in women with detrusor instability.

The phenomenon of urethral instability has been poorly defined and its significance is disputed. The aim of this study was to investigate the prevalence and significance of urethral instability in a group of women with idiopathic detrusor instability. Urethral instability was defined as a spontaneous fall in maximum urethral pressure of one-third or more, in the absence of detrusor activity, over a 2-min period. Urethral instability occurred in 42% of patients with detrusor instability and was strongly associated with the sequence of relaxation of the urethra prior to unprovoked detrusor contraction. Women with detrusor instability and a stable urethra exhibited primary contraction of the detrusor. The symptom of stress incontinence was more common in women with urethral instability. Women with detrusor instability may be subdivided into 2 groups on the basis of urethral instability, the presence of which suggests a primary dysfunction of the urethra. Such patients may derive more benefit from treatment with an alpha adrenoceptor agonist in addition to (or instead of) standard anticholinergic therapy.

Female↗
PubMed1992

The assessment of bladder neck movement in postpartum women using perineal ultrasonography.

Twenty-three postpartum women underwent perineal ultrasonography to determine bladder neck position at rest, on Valsalva and during pelvic floor contraction. On Valsalva, significant descent of the bladder neck and apposition to the symphysis pubis occurred. During pelvic floor contraction, there was significant elevation of the bladder neck; however, in approximately one-third of cases no movement was demonstrated. The bladder neck was shown to move through the arc of a circle whose center is the inferior border of the symphysis pubis. Perineal ultrasound provides a simple, objective way of measuring bladder neck elevation during pelvic floor contraction. This may be a more appropriate means of determining treatment outcome, in women undergoing conservative treatment for genuine stress incontinence, than measures of vaginal squeeze pressure.

Journal Article↗