不同溶栓剂治疗急性心肌梗死的比较

通过观察比较尿激酶（UK）、链激酶（SK）和重组组织型纤溶酶原激活剂（rt－PA）对急性心肌梗死（AMI）患者静脉溶栓的治疗结果,以探讨不同溶栓剂对AMI患者的疗效和安全性。     

New tetrahydroprotoberberine N-oxide alkaloids and cytotoxic constituents of Corydalis tashiroi

Three new tetrahydroprotoberberine N-oxide alkaloids, (-)- cis-corydalmine N-oxide, (-)- trans-corydalmine N-oxide, and (-)- trans-isocorypalmine N-oxide, along with three known benzo[ C]phenanthridine alkaloids, norsanguinarine, dihydrosanguinarine, and oxysanguinarine, six known berberine alkaloids, (-)-tetrahydropalmatine, (-)-corydalmine, (-)-scoulerine, (-)-corynoxidine, (-)-epicorynoxidine, palmatine, and protopine, have been isolated from the herb Corydalis tashiroi. The structures of these compounds were elucidated by spectroscopic analysis. Three of the isolated compounds show significant cytotoxic activities (ED (50) values < 4 microg/ml) against P-388, KB16, A549, and HT-29 cell lines.     

Cytotoxic terpenoids from the Formosan soft coral Nephthea brassica

Two new cytotoxic cembranoid diterpenes, brassicolide (1) and brassicolide acetate (2); a new cytotoxic sesquiterpene, (-)-4alpha-O-acetyl-selin-11-en (3); and six cytotoxic terpenoids, (-)-selin-11-en-4alpha-ol (4), 2-hydroxynephthenol (5), nephthenol (6), cembrene A (7), epoxycembrene A (8), and (-)-beta-elemene (9), have been isolated from the Formosan soft coral Nephthea brassica. The structures of compounds 1-9 were determined by spectral, chemical, and X-ray crystallographic analysis.     

Exploring the association between cardiovascular and other disease‐related risk factors in the psoriasis population: the need for increased understanding across the medical community

There is abundant and accumulating evidence on the classification of psoriasis as a systemic disease that exhibits a host of co‐morbidities. As a consequence, the second Interdisciplinary Conference on Co‐morbidities and Lifestyle Modification, convened by the International Psoriasis Council, has concluded that specialist physicians, primary care physicians and dermatologists are faced with an opportunity to impact, not just psoriasis disease understanding and management, but overall patient well‐being. The conference panel was represented by the disciplines of dermatology, cardiology, rheumatology, epidemiology, endocrinology, hepatology and gastroenterology, and medical specialists with particular expertise in obesity, diabetes mellitus, inflammation and genetics. The multiple co‐morbidities associated with psoriasis were reviewed with a view to identify possible mechanisms linking psoriatic disease with obesity, metabolic syndrome, diabetes, cardiovascular disease and non‐alcoholic fatty liver disease. Consensus was established on the association of psoriasis with other co‐morbidities and disease states. Consequently, there is a significant opportunity for specialist and primary care physicians to collaborate with dermatologists in the management of the overall health of psoriasis patients. First, there is an important need for physicians to routinely screen psoriasis patients for the multiple susceptibility risk factors and co‐morbidities associated with psoriasis. Second, the design and implementation of lifestyle modification plans including exercise, diet and the limitation of alcohol and tobacco intake, will not only benefit their general medical health but also their psoriasis.     

Defining a molecular phenotype for benign and malignant parathyroid tumors

BACKGROUND:

It is frequently difficult to establish histologically whether a parathyroid tumor is a parathyroid carcinoma, parathyromatosis, or an atypical adenoma. The authors asked whether these tumors have a distinctive molecular profile, whether benign tumors could be distinguished from malignant tumors, and whether parathyromatosis is a low‐grade parathyroid carcinoma or is benign tissue that can invade other organs.

METHODS:

Samples of parathyroid carcinoma, atypical adenoma, parathyromatosis, parathyroid adenoma, and hyperplasia were obtained for tissue microarray studies. The molecular expression of genes involved in parathyroid tumor progression (HRPT2 [“parafibromin”], galectin‐3, Ki‐67, Rb, p27, and mdm‐2) was investigated by immunohistochemistry.

RESULTS:

Complete loss of parafibromin expression was seen in 5 of 16 (31.3%) parathyroid carcinomas; all parathyromatosis, atypical adenomas, adenomas, and hyperplasia stained positive for parafibromin. Loss of Rb expression was seen in 5 (33.3%) of 15 parathyroid carcinomas and 1 (7.1%) of 14 parathyroid hyperplasias; all parathyromatosis, atypical adenomas, and adenomas stained positive. Galectin‐3 stained strongly positive in 14 (93.3%) of 15 parathyroid carcinomas, and positive in 3 (18.7%) of 16 cases of parathyromatosis, 2 (100%) of 2 atypical adenomas, 1 (5.6%) of 18 adenomas, and 2 (14.3%) of 14 hyperplasias. The Ki‐67 proliferative index was high in 9 (60%) of 15 parathyroid carcinomas, 1 (6.7%) of 15 cases of parathyromatosis, 1 (5.6%) of 18 adenomas, and no atypical adenomas or hyperplasia. P27 and mdm‐2 protein expression did not differ appreciably among the tumor types.

CONCLUSIONS:

No single diagnostic marker currently determines whether a parathyroid tumor is a parathyroid carcinoma, but loss of parafibromin and Rb expression, and overexpression of galectin‐3, generally distinguish parathyroid carcinoma from other parathyroid tumors. Parathyromatosis does not appear to be a low‐grade parathyroid carcinoma. Cancer 2009. © 2009 American Cancer Society.     

Risk of renal impairment after treatment with ibandronate versus zoledronic acid: a retrospective medical records review

Purpose  This retrospective study compared renal impairment rates in breast cancer, multiple myeloma, prostate cancer and non-small cell lung cancer patients treated with ibandronate or zoledronic acid. Study design  Medical records in two German oncology clinics from May 2001 to March 2006 were retrospectively reviewed. Creatinine measurements were analyzed from baseline (before bisphosphonate treatment) to last available measurement for each patient. The Cox proportional hazards model and the Andersen–Gill extension of the Cox model for multiple events analysis were used for multivariate analysis, which controlled for age, clinic site, primary cancer type, baseline SCr or GFR value, prior bisphosphonate use, concomitant use of drugs associated with acute renal failure, and renal-related comorbidities. Results  Of 333 patients, 109 received ibandronate and 256 received zoledronic acid (32 patients had both drugs). Compared with ibandronate, the zoledronic acid group had a significantly better baseline renal function and fewer patients had a history of renal disease. Zoledronic acid treatment increased the relative risk (RR) and the incidence rate (IR) of renal impairment by ~1.5-fold in all assessed patients (all tumors) compared with ibandronate. Multivariate analysis found significantly higher hazards ratios for zoledronic acid over ibandronate (two to sixfold), after adjusting for differences in characteristics between the two treatment groups. Conclusions  In this retrospective review, patients were significantly more likely to experience renal impairment with zoledronic acid than with ibandronate.     

Vascular endothelial growth factor and diabetes: the agonist versus antagonist paradox.

Much of the morbidity and mortality associated with diabetes is primarily attributable to sequelae of microvascular and macrovascular disease. Over the past decade, dramatic progress has been achieved in elucidating the fundamental processes underlying the pathogenesis of these complications. Angiogenic factors in particular now appear to play a pivotal role in the development of microvascular complications as well as the response to macrovascular disease. Hyperglycemia, other growth factors, advanced glycation end products, oxidative stress, and ischemia can increase growth factor expression. In some microvascular tissues, the result is pathologic neovascularization and increased vascular permeability. These responses account for much of the visual loss associated with diabetic retinopathy and may, in addition, serve a significant role in nephropathy and neuropathy. In contrast, recent data suggest that vascular collateralization resulting from ischemia-induced growth factor release in tissues compromised by macrovascular disease may be important in reducing clinical symptoms and tissue damage. This angiogenic response, which may be beneficial in coronary artery and peripheral limb disease, appears to be reduced in patients with diabetes. Thus, two apparently diametrically opposed therapeutic paradigms are arising for the treatment of vascular complications in diabetes. Indeed, growth factor antagonists have been used successfully in diabetes-related animal models to block angiogenic and permeability complications in the retina and kidney. Conversely, growth factor agonists have been successfully used to stimulate collateral vessel formation and reduce ischemic symptoms from macrovascular disease in the coronary arteries and peripheral limbs. Both of these approaches are currently being evaluated in clinical trials for their respective indications. Thus, as these divergent therapeutic modalities begin to enter the clinical arena, this apparent paradox necessitates careful consideration of the potential risks, benefits, and interactions of the opposing regimens. Using vascular endothelial growth factor as a classic example of growth factor involvement, we discuss the current preclinical and clinical data supporting these approaches and the implications arising from the probable coexistence of these two therapeutic modalities.     

Influence of intense light stimulation on trigeminal and cervical pain perception thresholds

Thirty-three migraineurs and 23 healthy controls were submitted to pressure algometry before and after light-induced discomfort was elicited by progressive light stimulation in a monoblind fashion. Pressure algometries were performed on the emergence of the supraorbital, infraorbital, mental and greater occipital nerves, and over the temporal muscles, always throughout the same sequence and from right to left. Measurements were carried out before and immediately after light stimulation and after 10 min of the second algometry. The final result for each site measured at each time-point was the mean of the three measurements. Light stimulation was carried out progressively until light-induced discomfort was reported, to a maximum of 20,000 lux. A heat-blocking glass protected patients' eyes. Migraineurs presented significant and persistent drops in pain perception thresholds after light stimulation, at all sites tested (P = 0.002 to < 0.0001). These drops were not seen in controls, in whom, conversely, a less significant increase was seen on right infraorbital and left temporal muscle sites. Our results indicate that in migraineurs, light may have a relevant role in trigeminal and cervical pain perception thresholds.