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41.
Summary Estrogen has an important role in stimulating the growth of breast carcinomas. Inhibition of estrogen production is therefore a logical treatment strategy. A number of selective inhibitors have been developed against aromatase, a cytochrome P-450 enzyme which catalyzes the rate limiting step in the biosynthesis of estrogens. The mechanisms of the aromatase reaction, current knowledge of the enzyme, and regulation of its expression are discussed as the basis for inhibitor development. Two classes of aromatase inhibitors, steroidal and non-steroidal compounds, are now coming into use. Among the steroid substrate analogues, 4-hydroxyandrostenedione (4-OHA) has been shown to be effective in breast cancer patients with advanced disease and was recently approved for treatment in the United Kingdom. Several different classes of compounds which act as aromatase inhibitors are currently in clinical trials and should provide breast cancer patients with a number of treatment options. Among these are highly potent and selective non-steroidal inhibitors which have recently been found to suppress plasma and urinary estrogens over 95% in breast cancer patients. The potency of these newer aromatase inhibitors provides the opportunity to determine whether complete suppression of estrogen production and action will result in enhanced tumor regression. 相似文献
42.
Trauma is a major cause of mortality and morbidity in the United States, with blunt traumatic injuries of the thoracic aorta continuing to occur despite the increased use of seatbelts and airbags. Emerging from crash analysis are effective interventions and provides increased awareness of the occult nature of these types of injuries. This article describes those interventions that healthcare providers must embed throughout the continuum of care for patients experiencing thoracic aortic injuries. Outcomes will be dependent upon the healthcare provider's knowledge of the physics of the event and the urgency of the diagnosis, as well as the ability to assess and manage all the variables involved. Current procedural issues are delineated and case studies are used to illustrate the processes of care needed by these patients. 相似文献
43.
Interactions Between Cytomegalovirus, Human Herpesvirus-6, and the Recurrence of Hepatitis C After Liver Transplantation 总被引:1,自引:0,他引:1
Atul Humar Deepali Kumar Janet Raboud Angela M. Caliendo George Moussa Gary Levy Tony Mazzulli 《American journal of transplantation》2002,2(5):461-466
Recurrence of hepatitis C (HCV) following liver transplantation is common. Herpesvirus reactivation following transplant may have an immunomodulatory effect resulting in increased HCV replication. We studied whether cytomegalovirus (CMV) and human herpesvirus-6 (HHV-6) may be associated with HCV recurrence and viral load after transplant. We prospectively followed 66 HCV liver-transplant recipients with serial viral load testing for CMV and HHV-6. Infection and viral load were correlated with the development of biopsy-proven HCV recurrence and HCV viral loads. Histologic recurrence of HCV occurred in 41/66 (62.1%) patients. In the primary analysis, CMV infection and disease, and HHV-6 infection were not associated with HCV recurrence. Peak CMV and HHV-6 viral loads were not significantly different in patients with and without recurrence. No correlation was observed between HCV viral loads at 1 and 3 months post-transplant and peak HHV-6 or CMV viral loads. In a subgroup analysis, HHV-6 infection was associated with the development of more severe recurrence (hepatitis and/or fibrosis score > or = 2) (p = 0.01). Also, fibrosis scores at last follow up were higher in patients with CMV disease (1.67 vs. 0.56; p = 0.016) and in patients with HHV-6 infection (1.18 vs. 0.55; p = 0.031). In conclusion, HHV-6 and CMV infection and viral load were not associated with increased overall rates of HCV recurrence or HCV viral load after liver transplantation but may be associated with more severe forms of recurrence. 相似文献
44.
Emiliano Sordi MD Angela Ferrari MD Domenico Piccolo MD Ketty Peris MD 《Dermatologic surgery》2002,28(12):1182-1183
45.
Carter R Coberley Gary A Puckrein Angela C Dobbs Matthew A McGinnis Sadie S Coberley Dexter W Shurney 《Disease management》2007,10(3):147-155
In addition to race and ethnicity, specific geographic regions are associated with poorer outcomes of care. Individuals with diabetes experiencing health disparities typically have worse long-term outcomes, such as increased diabetes complications and mortality. Zip code mapping, or geocoding, was utilized in this study to identify regions of the United States with high diabetes prevalence rates and to identify areas with high densities of minority populations. Use of this methodology to examine the effect of disease management on a large, diverse diabetes population revealed greater improvement in clinical testing rates in health disparity zones compared with members living outside of these areas. In particular, significant improvement was achieved by members living in minority zip codes and by members aged 65 years or older. These findings demonstrate that members living in areas of health disparity obtain even greater benefit from diabetes disease management program participation, helping to reduce gaps in care. 相似文献
46.
Sonja A Kotz Stefan Frisch D Yves von Cramon Angela D Friederici 《Journal of the International Neuropsychological Society》2003,9(7):1053-1060
The role of the basal ganglia in syntactic language processing was investigated with event-related brain potentials in fourteen neurologically impaired patients. Seven of these patients had basal ganglia lesions while 7 other patients primarily had lesions of the left temporo-parietal region excluding the basal ganglia. All patients listened to sentences that were either correct or included a verb argument structure violation. In previous experiments this type of violation elicited a biphasic pattern of an N400-P600 complex in young healthy participants. While the N400 may result from incorrect semantic-thematic role assignment, the P600 reflects the fact that verb information does not license the syntactic structure at present. Results of the patient experiment revealed a double dissociation: patients with left temporo-parietal lesions only show a P600, whereas patients with lesions of the basal ganglia showed no P600, but a negativity with extended duration that resembled an N400. The latter pattern not only confirms previous reports that the basal ganglia modulate the P600 but extends these results by showing that the N400 as a late semantic-thematic integration process appears partially modulated by the basal ganglia. 相似文献
47.
Angela Ameri 《Naunyn-Schmiedeberg's archives of pharmacology》1997,355(2):273-280
The effects of the Aconitum alkaloid 3-acetylaconitine on neuronal activity were investigated in the slice preparation and on cultivated neurons of rat
hippocampus by extracellular and patch-clamp recordings, respectively. 3-Acetylaconitine (0.01–1 μM) diminished the orthodromic
and antidromic population spike in a concentration-dependent manner. The inhibitory action of the drug was preceded by a transiently
enhanced excitability. The latency of onset of the inhibition was accelerated by increased stimulation frequency, whereas
recovery during washout of the alkaloid was accelerated by decreased stimulation frequency. Moreover, the inhibitory effect
of 3-acetylaconitine was evaluated in two different models of epileptiform activity induced either by blockade of GABA receptors
by bicuculline (10 μM) or by a nominal Mg2+-free bathing medium. In accordance with the activity-dependent mode of action, this compound abolished the synaptically evoked
population spikes in the presence of bicuculline or nominal Mg2+-free bathing medium, respectively. Whole-cell patch-clamp recordings revealed an interaction of 3-acetylaconitine with the
voltage-dependent sodium channel. At a concentration of 1 μM, 3-acetylaconitine did not affect the peak amplitude of the sodium
current, but shifted the current-voltage relationship in the hyperpolarized direction such that sodium currents were already
activated at the resting potential.
Received: 22 July 1996 / Accepted: 14 October 1996 相似文献
48.
49.
Zenab Amin Ralitza Gueorguieva Angela Cappiello Kathryn A Czarkowski Stephanie Stiklus George M Anderson Frederick Naftolin C Neill Epperson 《Neuropsychopharmacology》2006,31(11):2489-2497
Despite an abundance of data in animals, there is little research in humans regarding how estrogen and serotonin (5-HT) may interact to influence cognition. Through the use of estrogen treatment (ET) and tryptophan depletion (TRP-D) in a within-subject design involving healthy menopausal women, we have manipulated both estrogen and 5-HT in order to evaluate their individual and joint effects. Although neither manipulation influenced visuospatial learning, a significant interaction suggested that estrogen exerted a protective effect on verbal memory, such that TRP-D impaired performance to a greater extent before the administration of ET. In consonance with this finding, ET was associated with a small, but positive mood effect on the day following active TRP-D. In addition, ET significantly improved letter-cued verbal fluency with and without TRP-D. Finally, time since last menstrual period was significantly associated with verbal memory scores, such that longer length of hypogonadism resulted in decreased verbal memory performance. These data support the interaction of estrogen and 5-HT in nonreproductive behavior in humans as well as highlight the role of ovarian steroids in cognition. 相似文献
50.
Claudio R Cernea Alberto R Ferraz Inês V de Castro Miriam N Sotto Angela F Logullo Carlos E Bacchi André S Potenza 《Otolaryngology--head and neck surgery》2006,134(3):471-475
BACKGROUND: Some skin carcinomas may be very aggressive. Increased expression of the protein p53 has been associated with tumor aggressiveness. In this study, p53 expression was evaluated in basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) with skull base invasion, and was compared to tumors with good outcome. STUDY DESIGN AND SETTING: Expression of p53 was immunohistochemically analyzed and it was reported as present or absent in 24 BCC and 11 SCC with skull base invasion. Control group (good outcome) included 23 BCC and 10 SCC. RESULTS: Expression of p53 was noted in 70.83% of BCC with skull base invasion, compared to 43.48% in the control group (P = 0.058). Regarding SCC, p53 positivity was noted in only 9.09% of SCC with skull base invasion, compared to 40.00% in the control group (P = 0.149). CONCLUSIONS: In this study, p53 expression was more common among BCC with skull base invasion, compared to controls with good outcome, and the difference was considered marginally significant. This proportion was reversed in SCC, but the difference was not statistically significant. EBM rating: B-3b. 相似文献