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51.
52.
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
53.
Robert D Bourke MB BS John Pyle MB BS; FRACO FRACS † 《Clinical & experimental ophthalmology》1994,22(1):77-80
Herpes zoster ophthalmicus (HZO) commonly causes isolated ophthalmoplegic syndromes. Visual loss caused by optic neuritis secondary to HZO can be reversible or irreversible. HZO rarely presents as an orbital apex syndrome, when an association with meningo-encephalitis has been reported. We report a case of orbital apex syndrome secondary to HZO treated with systemic steroids and acyclovir. Our patient suffered no systemic complications and displayed a rapid resolution of optic neuropathy. We discuss this case in the light of previous reports and explore the possible pathogenic mechanisms involved. 相似文献
54.
55.
Suppurative corneal ulceration in Bangladesh 总被引:8,自引:0,他引:8
AAS Dunlop MB BS ED Wright MRCPath † SA Howlader‡ I Nazrul‡ R Husain‡ K McClellan FRACO § FA Billson FRACO § 《Clinical & experimental ophthalmology》1994,22(2):105-110
Suppurative keratitis is an important preventable cause of blindness, particularly in the developing world. This study analyses 142 cases of suppurative keratitis referred to Chittagong Eye Infirmary, Bangladesh. Some 53.5% of cases were bacterial and 35.9% were fungal. The five most common pathogens were: Pseudomonas sp. 24%, Streptococcus pneumoniae 17%, Aspergillus sp. 13%, Fusarium sp. 7% and Curvularia sp. 6%. Gram stain and culture results were consistent in 62.6% of cases. Previous antibiotic treatment was a significant factor for failure of culture isolation and less so for Gram stain failure. On Gram stain, 55.9% of pseudomonal cases were missed, but only 2% of fungal cases were missed. Over all, Gram stain had a sensitivity of 62% and positive predictive value of 84% for bacterial cases, and 98% and 94% for fungal cases, respectively. Fungal ulcers were typically filamentous, but an antecedent history of trauma was not common. The most frequent injury was due to rice grains, but the inoculum appeared to be introduced during eye washing with contaminated water. Pseudomonal ulcers occurred most frequently in the monsoon season, and Fusarium cases were seen only in the hot, dry season. 相似文献
56.
Mark Ellis FRACO FRACS Ross Drewe MB BS DO † Justin O'Day FRACO FRACS 《Clinical & experimental ophthalmology》1994,22(2):119-123
Desmoplastic malignant melanoma (DMM) is a rare variant of spindle cell melanoma. We report a case of DMM of the forehead secondarily involving the orbit. The diagnosis was based on light microscopic features, including prominent peripheral cell nest formation and spindle cell fascicles in densely collagenous stroma. Immunohistochemical studies showed strong uniform staining for S100 antigen throughout the tumour. It was negative for HMB 45, smooth muscle actin, desmin, cytokeratins and Type IV collagen. Electron microscopy showed neither melanosomes nor myelin figures. The clinical and histological characteristics of desmoplastic malignant melanoma, and its differential diagnosis of malignant schwannoma, are discussed. DMM has a poor prognosis, since it tends to invade deeply, recur locally and metastasise readily. 相似文献
57.
Maryla Z Stelmach MB BS Justin O'Day FRACO FRACS † Hugh Ryan FRACO FRACS ‡ 《Clinical & experimental ophthalmology》1994,22(2):139-143
The history and clinical findings are presented of a patient who suffered from the uveal effusion syndrome over a 10-year period from 1956. The funduscopic appearance is illustrated both at the time of initial presentation and 36 years later. This condition typically affects healthy middle-aged men and causes recurrent, spontaneous, serous retinal and ciliochoroidal detachments, often resulting in significant visual impairment. Two separate hypotheses have been postulated to explain the pathogenesis of the uveal effusion syndrome, one relating to abnormally thickened sclera, the other to chronic bulbar hypotony. Both are discussed, as is the rationale behind the current management of this unusual condition. 相似文献
58.
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
59.
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
60.
Dawn Hastreiter MD PhD ; Jeannie Chao BS ; QI Wang MD ; Richard M. Ozuna MD ; Myron Spector PhD 《Wound repair and regeneration》2004,12(4):430-438
That a contractile actin isoform has been found in cells of other cartilage tissues in healing and disease states prompted this investigation of the presence of alpha-smooth muscle actin (alpha-SMA) in pathological human intervertebral disc tissue. The presence of this isoform has been reported in human intervertebral disc specimens obtained at autopsy from subjects for whom there were no reported symptoms. An objective of this study was to evaluate the cell density and percentage of alpha-SMA-containing cells in pathological nucleus pulposus tissue obtained from lumbar disc surgery from 17 patients. Additionally, explants of nucleus pulposus material were cultured to determine how alpha-SMA expression changed with time in vitro. Seventy-six 5-mm diameter explants (approximately 2 mm thick) pooled from six lumbar surgeries were cultured for 1, 2, 4, or 6 weeks. Microtomed sections of paraffin-embedded specimens were stained with hematoxylin and eosin or a monoclonal antibody to alpha-SMA. Histologically, cells were categorized as to alpha-SMA phenotype (positive or negative), and the areal cell density was determined. The evaluation of the cultured nucleus pulposus explants also included documentation of the percentage of cells that were round or elongated and the percentage of the cells that were part of a group (group: >/= 2 cells). Every nucleus pulposus section exhibited the presence of alpha-SMA-containing cells, which accounted for approximately 24 percent of the cells in vivo. In vivo, the cell density was significantly higher in older individuals (p = 0.02). The average time for cell outgrowth from the explants was 8.6 days. Approximately 10-15 percent of the cells in the explants stained positive for alpha-SMA. The time in culture had no significant effect on any of the outcome measures except the percentage of alpha-SMA-containing cells that were round (p = 0.008), with values decreasing through 4 weeks and then slightly rising at 6 weeks. The role of alpha-SMA in intervertebral disc pathology warrants further investigation. 相似文献