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51.
Rolf W. Hartmann Martin Frotscher Dorothea Ledergerber Gerald A. Wchter Gertrud L. Grün Tom F. Sergejew 《Archiv der Pharmazie》1996,329(5):251-261
In search of potential drugs for the treatment of estrogen- and androgen-dependent cancer as well as the prophylaxis of metastases, tetralones, tetralins, and dihydronaphthalenes bearing a OCH3 substituent at the benzene nucleus and an imidazol-4-yl, imidazol-1-yl, or 1,2,4-triazol-1-yl substituent in 2-position were synthesized with and without C1-spacer between the rings (compounds 2 – 26 ). The compounds were tested in vitro for inhibition of the three target enzymes P450 arom (human placental microsomes), P450 17 (rat testicular microsomes), and P450 TxA2 (citrated human whole blood). To examine selectivity, some compounds were further tested in vitro for inhibition of P450 18 (bovine adrenal mitochondria), P450 see (bovine adrenal mitochondria) and corticoid formation (aldosterone, corticosterone; ACTH stimulated rat adrenal tissue). In vivo, selected compounds were examined in Sprague Dawley rats regarding P450 TxA2 inhibition, reduction of plasma testosterone concentration, antiuterotrophic activity (inhibition of the uterotrophic activity of androstenedione), reduction of plasma estradiol concentration (pregnant mares' serum gonadotropin-primed rats), and mammary tumor inhibiting activity (dimethylbenzanthracene-induced tumor; pre- and postmenopausal model). In the series of imidazol-4-yl compounds, which represent a novelty in the field of azole inhibitors of steroidogenic P450 enzymes, strong inhibitors of P450 arom and/or P450 17 were found: 7-OCH3-2-(imidazol-4-ylmethylene)-1-tetralone ( 4 ) and 7-OCH3-2-(imidazol-4-ylmethyl)-tetralin ( 12 ) are among the most potent inhibitors of P450 arom in vitro known so far. Compound 4 is a selective inhibitor, whereas 12 shows in addition strong inhibition of P450 17. In contrast to 12 , the 6-OCH3 derivative (compound 11 ) is a selective inhibitor of P450 17, being 50 times more potent than ketoconazole. Some imidazol-1-yl compounds show a marked inhibition of P450 TxA2: 2-(imidazol-1-ylmethyl)-1-tetralone ( 13 ) is a selective inhibitor of P450 TxA2, whereas 7-OCH3-2-(imidazol-1-ylmethyl)-tetralin ( 17 ) as well as 2-(imidazol-1-ylmethyl)-tetralin ( 16 ) and 7-OCH3-2-imidazol-1-yl-3,4-dihydronaphthalene ( 25 ) additionally show strong inhibition of P450 arom and P450 17. Regarding the other steroidogenic P450 enzymes as well as corticosterone formation, the compounds show only little inhibitory activity. Aldosterone formation, however, is inhibited at low concentrations. Nevertheless, 4 and 12 are more selective, i.e. inhibit aldosterone synthesis less than the well known inhibitor of P450 arom fadrozole. The compounds show activity in the aforementioned in vivo tests. 相似文献
52.
K Kondoh S Sasaki T Oku S Minohara S Hasegawa Y Sawada M Morita A Takeuchi 《Kyobu geka. The Japanese journal of thoracic surgery》1992,45(7):565-9; discussion 569-72
In six hundred and six consecutive patients undergoing coronary artery bypass grafting (CABG) within the past 17 years (May 1974 to March 1991), repeated CABG were performed on 10 patients (1.65%). The main reasons for repeated CABG were graft failure (GF) in 8, progression of native disease (NP) in 5 and incomplete revascularization (IR) in 3 patients. The incidence of GF was high either within a half year or around 5 years after CABG. Although all patients survived from reoperation, four patients continued to have mild angina pectoris. When the recurrence of angina is noted after CABG, coronary arteriography and if necessary PTCA should be done as soon as possible. If a second surgery is inevitable, maximum utilization of arterial graft and accomplishment of complete revascularization are emphasized. 相似文献
53.
T Watanabe T Abe M Tanaka E Takeuchi K Yasuura M Sawazaki 《Kyobu geka. The Japanese journal of thoracic surgery》1990,43(8):645-652
Late results after total correction of tetralogy of Fallot over ten year follow up of 84 patients were discussed. No late death was experienced and 95.1% of these patients are now in NYHA class I. Reoperations were performed in 7 cases (8.3%) in which six had had residual shunt and one had had sick sinus syndrome and had VVI pacemaker implantation. Ten cases had over 90% of ratio of right ventricular pressure to systemic pressure in systole in their cardiac catheterization about 40 days after correction. In spite of this high pressure ratio, all cases are now in NYHA class I. We conclude that there is a possibility of enabling to preserve pulmonary valve function by adopting smaller criteria than the Pacifico's criteria. 相似文献
54.
K Tsuchiya T Takeuchi A Takazawa Y Iida T Seki 《Kyobu geka. The Japanese journal of thoracic surgery》1990,43(4):325-328
A 57-year-old male patient with aortic regurgitation and aneurysm of the ascending aorta and the aortic arch underwent aortic valve replacement and graft replacement from the ascending aorta to the aortic arch. The operation was done using cardio-pulmonary bypass and selective cerebral perfusion with deep hypothermia. Postoperative DSA revealed no dilatation of the sinus Valsalva and a good configuration of the anastomosis. It seems that selective cerebral perfusion with deep hypothermia is a safe method to prevent cerebral damage in a case of arch aneurysm. 相似文献
55.
The development of the quality improvement programme of the Paediatric Association of the Netherlands is described within the setting of the national programme of the Dutch government. The programme is based on four pillars: site visits by peers (visitatie), continuous medical and professional education, development of clinical (evidence based) guidelines and patient safety with complication registration. The site visits by peers play a central role in assessing the quality improvement activities in hospital based paediatric care. The self assessment approach and the confidential character of the visits are well received by the surveyed specialists. Recent inclusion of quality criteria in the legally required 5 yearly medical specialist recertification process has boosted the care for quality, which could serve as example for other countries. 相似文献
56.
Melanie Inkster Alan Montgomery Peter Donnan Tom MacDonald Frank Sullivan Tom Fahey 《The British journal of general practice》2005,55(521):931-937
BACKGROUND: Studies show that 60-75% of treated patients with hypertension in general practice, still do not reach the recommended blood pressure targets of <150/90 mmHg. AIM: To investigate aspects of hypertension management in relation to sociodemographic variables, antihypertensive drug treatment, and organisational factors in primary care. DESIGN OF STUDY: Observational study over 3 years. SETTING: Eight general practices in Tayside, UK. METHOD: Participants were 560 randomly selected patients aged 40-79 years receiving treatment for hypertension. The outcome measurement was blood pressure control, expressed in binary form based on the British Hypertension Society audit standard of <150/90 mmHg. RESULTS: Of 536 eligible patients, 261 (49%) were defined as having inadequate blood pressure control at the end of the study period. No significant associations were discovered with sex, age, deprivation score and comorbidity. In those patients with inadequate control, 30% had no modifications to their drug treatment during the study period. Blood pressure control at the end of the study period was not associated with number of antihypertensive drugs taken or number of antihypertensive drug modifications. The mean number of clinician contacts was 11 (standard deviation = 8), and mean continuity in primary care was high, although this was not associated with improved blood pressure control. A higher proportion of hypertension-related consultations were associated with increased odds of having inadequate blood pressure control. CONCLUSION: Achieving adequate blood pressure control continues to represent a substantial health problem in a significant proportion of the hypertensive population. Patient, physician and organisational elements play a role in ensuring effective delivery of hypertension care in the community. 相似文献
57.
The effects of prior 24-hour ureteral obstruction on ischemic renal damage were studied in rats. Rats were divided into 6 groups with different times of ischemia (0, 60 and 90 min) and with or without 24-hour ureteral obstruction. Following a 4-week recovery period, contralateral nephrectomy was performed and the rat was sacrificed 24 h later for the determination of serum creatinine and for histologic examination of the affected kidney. A preceding ureteral obstruction for 24 h made no difference to the renal damage with 60 min of ischemia or without ischemia. However, kidneys with 90 min of ischemia and 24 h of ureteral obstruction were more damaged than those with 90 min of ischemia only. These results suggested that the hydronephrotic kidney was more susceptible to long periods of ischemia than the normal kidney. 相似文献
58.
Fine-needle aspiration biopsy, used extensively for evaluating head and neck masses in adults, also provides an excellent minimally invasive means of evaluating infants with neck masses and torticollis. Three cases of torticollis involving infants are presented. In each case, fine-needle aspiration revealed a benign fibrous lesion, ruling out malignancy. The remaining cytologic differential diagnosis between infantile fibromatosis, fibromatosis colli, and calcifying aponeurotic fibrosis is discussed, with mention of the possible causes of and treatment for congenital torticollis. We conclude that fine-needle aspiration provides a fast and accurate diagnosis of neck masses in infants who have congenital torticollis, thereby avoiding surgical procedures in this very young age group. 相似文献
59.
Gary Coleman Tom A. Gardiner Ariel Boutaud Alan W. Stitt 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2007,245(4):581-587
Background A recombinant form of the α2(IV)NC1 domain of type IV collagen has been shown to have potent anti-angiogenic activity although
this peptide has not been studied in the context of proliferative retinopathies. In the current investigation we examined
the potential for α2(IV)NC1 to regulate retinal microvascular endothelial cell function using a range of in vitro and in vivo
assay systems.
Materials and methods α2(IV)NC1 at concentrations between 0.1 and 1 μg/ml was added to retinal microvascular endothelial cells (RMECs) followed
by assessment of cell attachment, proliferation and survival. This agent was also tested within a novel in vitro three-dimensional
retinal angiogenesis assay and the number of angiogenic sprouts quantified. α2(IV)NC1 was also delivered intra-vitreally to
mice with oxygen-induced proliferative retinopathy (OIR) and neovascularisation evaluated in comparison with vehicle-treated
controls.
Results RMECs treated with α2(IV)NC1 (0.1, 0.5 and 1 μg/ml) showed delayed attachment at 3 h post-seeding, although this deficit had
been restored at the 6-h time point. BrdU assay of DNA replication revealed that confluent RMECs treated with α2(IV)NC1 showed
no measurable response in comparison with vehicle-treated controls. By contrast, proliferation of sub-confluent RMECs was
significantly reduced by α2(IV)NC1 at 0.5 μg/ml (P<0.01). α2(IV)NC1 also induced apoptosis in RMECs and inhibited angiogenesis of pre-existing retinal vascular networks in
vitro (P<0.001). Intra-vitreal injection of α2(IV)NC1 in the OIR model significantly inhibited pre-retinal neovascularisation compared
with vehicle-treated controls (P<0.001).
Conclusion α2(IV)NC1 inhibits angiogenesis in the retinal microvasculature. This recombinant protein has potential for the treatment
of neovascularisation in proliferative retinopathies.
BioStratum Inc. did not sponsor this research in any way. None of the authors are paid consultants with this company. 相似文献
60.
T Okamura T Takeuchi O Nishii T Yaginuma T Kawana 《Nippon Sanka Fujinka Gakkai zasshi》1987,39(11):2059-2065
Ten puerperal women were put on a 1,200 kcal diet per day for 3 days followed by an ordinary 1,800 kcal diet per day for 3 days [Low-Caloric (LC) group]. Fifteen puerperal women were put on an ordinary 1,800 kcal diet per day for 6 days[Ordinary-Caloric (OC) group]. All of the women took breakfast at 7:30 am, blood was drawn at 9:30 am and then the breasts were milked for 2 minutes with an electric breast pump starting on the day of delivery (Day 0) and continuing to Day 5. Four women in the LC and OC groups underwent a thyrotropin-releasing hormone (TRH) stimulation test on Days 1 and 3. Serum prolactin (PRL) and TSH levels in the LC group tended to be much lower than those of the OC group during the test period. Serum PRL and TSH release response to TRH in the OC group were much higher than in the LC group on Days 1 and 3. No significant difference was noted between the OC and LC groups in serum estradiol (E2) and cortisol levels from Day 0 to Day 5. The milk volume in the LC group was significantly less than in the OC group on Day 1. Analysis of milk specimen components revealed little difference between the OC and LC groups. These results suggested that a low-caloric diet may suppress PRL, TSH and milk secretion and may not be useful for breast-feeding. 相似文献