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81.
Law MP Osman S Pike VW Davenport RJ Cunningham VJ Rimoldi O Rhodes CG Giardinà D Camici PG 《European journal of nuclear medicine》2000,27(1):7-17
Dysfunction of the sympathetic nervous system underlies a number of myocardial disorders. Positron emission tomography (PET) offers a way of assessing receptor function non-invasively in humans, but there are no PET radioligands for assessing myocardial alpha-adrenoceptors. GB67, a structural and pharmacological analogue of the alpha 1-adrenoceptor antagonist prazosin, was labelled with positron-emitting carbon-11 (t1/2 = 20.4 min) by 11C-methylation of N-desmethylamido-GB67 (GB99). [11C]GB67 was injected intravenously into conscious rats. Serial arterial blood samples were taken. Rats were killed and tissues removed to determine radioactivity. The percentages of unchanged [11C]GB67 and its radioactive metabolites in plasma and tissues were assessed by HPLC. Plasma clearance of radioactivity was rapid. Myocardial uptake was maximal at 1-2 min and decreased slowly during 60 min. Predosing with adrenoceptor antagonists demonstrated selectivity for myocardial alpha 1-adrenoceptors. GB67 and prazosin blocked uptake of radioactivity; the non-selective antagonist, phentolamine, partially blocked uptake; the alpha 2-adrenoceptor antagonist, RX 821002, only blocked uptake at high dose and the beta-adrenoceptor antagonist, CGP 12177, had no effect. Additionally, injection of prazosin at 20 min after radioligand displaced radioactivity. In vivo competition curves obtained by injecting [11C]GB67 with varying amounts of either unlabelled GB67 or its precursor GB99 were fitted to a competitive binding model to provide estimates of the maximum number of binding sites (Bmax) and half saturation doses (K) for myocardium. Assuming a tissue protein content of 10%, the values of Bmax [approximately 13 pmol.(g tissue)-1[ were similar to those ]50-170 fmol.(mg protein)-1] reported for myocardial alpha 1-adrenoceptors assessed in vitro. Both GB67 and its precursor GB99 had high affinity for alpha 1-adrenoceptors [KGB67 = 1.5 nmol.(kg body weight)-1, KGB99 = 4.8 nmol.(kg body weight)-1]. HPLC demonstrated four radioactive metabolites in plasma. [11C]GB67 was 80% of the radioactivity at 5 min and 50% at 45 min. No radioactive metabolites were detected in myocardium up to 60 min after injection. [11C]GB67 was assessed in two male human volunteers. PET demonstrated high myocardial uptake. The profile of radioactive metabolites in plasma was comparable to that in the rat, although metabolism was slower in humans. Thus, [11C]GB67 is a promising radioligand for assessing alpha 1-adrenoceptors in human myocardium with PET. 相似文献
82.
Probst-Hensch NM Pike MC McKean-Cowdin R Stanczyk FZ Kolonel LN Henderson BE 《British journal of cancer》2000,82(11):1867-1870
Breast cancer incidence in Japanese-American women is approaching that of US Whites. We investigated whether this shift is paralleled by similar post-menopausal plasma hormone levels in the two ethnic groups. We also included African-American and Latina women to further our understanding of possible ethnic differences in oestrogen metabolism. We measured androstenedione (A), oestrone (E1) and oestradiol (E2) in 30 Japanese-American, 39 non-Latina White ('White'), 66 African-American and 58 Latina women. The (age-adjusted) geometric mean E1 levels were 34 pg ml(-1) in Japanese-Americans, 28 pg ml(-1) in Whites, 35 pg ml(-1) in African-Americans and 31 pg ml(-1) in Latinas. After adjustment for body mass index, Japanese-Americans had the highest mean E1 value of all groups and this was statistically significantly greater than the value for Whites (P(t-test) = 0.05). The geometric mean A concentrations were also highest in Japanese-Americans. There was little ethnic difference in E2 levels. In conclusion, post-menopausal plasma oestrogen levels in Japanese-American women are at least as high as those in Whites. 相似文献
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The cyclic production of estrogen and progesterone by the premenopausal ovary accounts for the steep rise in breast cancer risk in premenopausal women. These hormones are breast cell mitogens. By reducing exposure to these ovarian hormones, agonists of luteinizing hormone-releasing hormone (LHRH) given to suppress ovarian function may prove useful in cancer prevention. To prevent deleterious effects of hypoestrogenemia, the addition of low-dose hormone replacement to the LHRH agonist appears necessary. Pilot data with such an approach indicates it is feasible and reduces mammographic densities. 相似文献
86.
Gregory K. Pike Justin R. Bessell George Mathew David I. Watson Phillip C. Mitchell Glyn G. Jamieson 《ANZ journal of surgery》1996,66(2):94-96
Background: Venous thromboembolic complications may be more common after laparoscopic surgical techniques, possibly due to changes in venous flow and blood coagulability. Methods: This study assessed fibrinogen, cross-linked fibrin degradation products (D-dimer), prothrombin international normalized ratio (INR), activated partial thromboplastin time (APTT) and platelets, during and after both open and laparoscopic Nissen fundoplication to determine whether coagulability is increased by the laparoscopic approach. Results: Seven patients underwent open and thirteen underwent laparoscopic Nissen fundoplication. Fibrinogen levels following open fundoplication fell from 2.8 ± 0.3 g/L pre-operatively to 2.0 ± 0.3 g/L following skin incision, and then increased to 4.1 ± 0.4 g/L on the first postoperative day. Similar changes in fibrinogen occurred following laparoscopic fundoplication (2.7 ± 0.2, 2.5 ± 0.2 and 3.8 ± 0.4 g/L, respectively). No significant changes in the other coagulation indices were observed. Conclusions: These results demonstrate hypercoagulability on the first postoperative day, irrespective of the operative technique. No differences between the results following laparoscopic and open fundoplication were demonstrated. 相似文献
87.
Breast-cancer incidence and mortality rates in different countries were found to be correlated with height, weight and age at menarche, all of which have been identified as risk factors in cohort or case-control studies of breast cancer. There were, however, correlations with total fat and animal protein consumption per capita even after controlling for the 3 anthropometric variables. This suggests that, while some of the effects of diet on breast-cancer rates may be mediated through effects on these known risk factors, there may be more direct effects as well. 相似文献
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