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At least 91 records · Page 5Linked to original sources

Skeletal health in postmenopausal survivors of early breast cancer.

Estrogen plays an important role in the skeletal health of all women. Many therapies used in the treatment of breast cancer reduce estrogen levels and have the potential to affect bone negatively by increasing the risk of osteoporosis and associated bone fractures. The long-term effects of systemic endocrine therapy on bone, therefore, are an important consideration in the adjuvant setting. Tamoxifen has been shown to have a moderate protective effect on postmenopausal bone due to its partial estrogen agonist activity; however, its long-term use is potentially associated with negative side effects, such as an increased risk of thromboembolic disease and endometrial cancer. Newer agents, the third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, for example, do not possess estrogen agonist effects and have improved breast cancer outcomes when compared to the standard 5 years of tamoxifen. However, patients treated with adjuvant AIs have been shown to have an increased incidence of osteoporosis and osteoporotic fractures. In order to select the optimal adjuvant therapy for each patient, it is important to assess the overall risk:benefit ratio for each endocrine strategy. All postmenopausal women should follow published guidelines to assess the risk of osteoporosis and, where appropriate, they should receive bone mineral density monitoring. Postmenopausal women with breast cancer who are at increased risk of osteoporotic fracture should be identified and managed with appropriate nonpharmacologic and pharmacologic measures.

Aged↗

Review: aromatase inhibitors for ovulation induction.

CONTEXT: For the last 40 yr, the first line of treatment for anovulation in infertile women has been clomiphene citrate (CC). CC is a safe, effective oral agent but is known to have relatively common antiestrogenic endometrial and cervical mucous side effects that could prevent pregnancy in the face of successful ovulation. In addition, there is a significant risk of multiple pregnancy with CC, compared with natural cycles. Because of these problems, we proposed the concept of aromatase inhibition as a new method of ovulation induction that could avoid many of the adverse effects of CC. The objective of this review was to describe the different physiological mechanisms of action for CC and aromatase inhibitors (AIs) and compare studies of efficacy for both agents for ovulation induction. EVIDENCE ACQUISITION: We conducted a systematic review of all the published studies, both controlled and noncontrolled, comparing CC and AI treatment, either alone or in combination with gonadotropins, for ovulation induction or augmentation, identified through the Entrez-PubMed search engine. EVIDENCE SYNTHESIS: Because of the recent acceptance of the concept of using AIs for ovulation induction, few controlled studies were identified, and the rest of the studies were pilot or preliminary comparisons. Based on these studies, it appears that AIs are as effective as CC in inducing ovulation, are devoid of any antiestrogenic side effects, result in lower serum estrogen concentrations, and are associated with good pregnancy rates with a lower incidence of multiple pregnancy than CC. When combined with gonadotropins for assisted reproductive technologies, AIs reduce the dose of FSH required for optimal follicle recruitment and improve the response to FSH in poor responders. CONCLUSIONS: Preliminary evidence suggests that AIs may replace CC in the future because of similar efficacy with a reduced side effect profile. Although worldwide experience with AIs for ovulation induction is increasing, at present, definitive studies in the form of randomized controlled trials comparing CC with AIs are lacking.

Anovulation↗

[Study of TRAIL receptors expression on the mononuclear cells from multiple myeloma patients and KM3 cells].

OBJECTIVE: To study the differential expression of four TRAIL receptors on bone marrow mononuclear cells (BMMNC) from multiple myeloma (MM) patients and myeloma cell line KM3 cells, to compare their altered expressions after chemotherapy and to explore the mechanisms by which TRAIL selectively kills tumor cells. METHODS: Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry were used to investigate the expression of four TRAIL receptors on BMMNCs in 23 MM patients, KM3 cells and 15 controls, and the changes of their expression pattern after chemotherapy and after incubation of KM3 cells with sub-clinical concentration of doxorubicin. RESULTS: DR4 and DR5 were highly expressed on KM3 cells with no expression of DcR1 and DcR2. Expressions of DR4 and DR5 on BMMNCs from MM patients were higher and expression of DcR1 and DcR2 were lower than that of controls (P < 0.05). The expression of DR5 on MM and KM3 cells was up-regulated after chemotherapy and exposure to doxorubicin (P < 0. 05). CONCLUSIONS: The expressions of four TRAIL receptors on myeloma cells and normal controls were different, which might account for the selective killing effect of TRAIL on MM cells. Up-regulated DR5 on KM3 cells after incubating with doxorubicin and after chemotherapy suggests the cytotoxic agents might enhance the apoptosis of MM cells.

Antineoplastic Agents↗

Allergic contact dermatitis to polyethylene glycol and nitrofurazone.

We report a case of worsening dermatitis after the application of an antibiotic ointment (Furacin) containing furazone and polyethylene glycol. Patch tests to nickel sulfate, potassium dischromate, chloride cobalt, Furacin, nitrofurazone 1% petrolatum, polyethylene glycol mix 4% petrolatum, polyethylene glycol (PEG) 300 4% petrolatum, and PEG 400 as is (ai) were positive. The use of topical agents containing nitrofurazone or polyethylene glycol on damaged skin may predispose to contact allergy. We discuss the sensitizing properties of nitrofurazone and polyethylene glycol.

Anti-Infective Agents, Local↗

Emerging role of aromatase inhibitors in the adjuvant setting.

Aromatase inhibitors (AIs) have been approved as second-line treatment for estrogen receptor-positive (ER+) metastatic breast cancer after first-line treatment with the selective estrogen receptor modulator (SERM) tamoxifen. Anastrozole and letrozole have also recently been widely approved as first-line endocrine therapy for postmenopausal women with hormone receptor-positive metastatic breast cancer. The three third-generation selective oral AIs approved for use in the United States include two nonsteroidal agents, anastrozole (Arimidex) and letrozole (Femara), and the irreversible steroidal inhibitor exemestane (Aromasin). Several major ongoing clinical trials with a variety of treatment regimens are comparing the relative efficacy of tamoxifen with the steroidal and nonsteroidal AIs in the adjuvant setting. The first strategy compares an AI against tamoxifen directly. Among these are the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial (anastrozole), the BIG FEMTA (Femara-Tamoxifen Breast International Group) trial (letrozole), and the EXEM and TEAM (exemestane) trials. A second strategy is examining the use of an AI as an extension after the initial 5 years of tamoxifen. Examples of this trial design are the MA-17 (letrozole) and the National Surgical Adjuvant Breast and Bowel Project (NSABP B-33, exemestane) trials. A third approach is the use of these agents in sequence with tamoxifen as therapy within the initial 5 postoperative years. Examples of this approach are the International Collaboration Cancer Group trial (tamoxifen for 2-3 years followed by either tamoxifen or exemestane for the remainder of the 5-year period), the BIG FEMTA trial (patients are crossed over from tamoxifen to Ietrozole or letrozole to tamoxifen), and the Arimidex-Nolvadex (ARNO) trial (patients receiving tamoxifen are randomized either to continue with tamoxifen or to switch to anastrozole). A single trial is comparing tamoxifen and anastrozole as initial 5-year therapy, or a combination of the two. The study addressing this design is the ATAC trial. Finally, a small trial in Norway is comparing 2 years of an AI versus a placebo in very low-risk patients with receptor-positive breast tumors. Most adjuvant trials have companion studies associated with the main protocol. These are to determine the end-organ effects of the inhibitors and include measurements of quality of life, bone and lipid metabolism, and endometrial effects. This review addresses the clinical implications of these studies of AIs.

Antineoplastic Agents↗

Neoplastic transformation of Chinese hamster cells in vitro after treatment with flavoring agents.

Chinese hamster B241 cells were treated with 5 nM allylisothiocyanate (AI) or 10 nM trans-cinnamaldehyde (CA) and surviving cells were cultivated for generations until the cells acquired the characteristics of transformed cells based on in vitro criteria: increase in (a) saturation density in monolayer culture, (b) plating efficiency at low serum level and (c) colony forming efficiency (CFE) in soft agar medium. When the values of CFE of the treated cells had become significantly high, anchorage-independent colonies were isolated, propagated and then subjected to an assay for neoplastic transformation. The anchorage-independent clonal cells (CH-AI-AG+-1 and CH-CA-AG+-2) were subcutaneously injected into a suprascapular site in nude mice. The mice were maintained in an SPF animal care facility and observed for tumor formation. Growth of neoplasm at the injection sites was observed in 6 out of 7 mice and in all of the 6 mice injected with CA- and AI-transformed cells, respectively, during 3 to 8 months after the injection, as compared with 1 out of 6 mice injected with untreated control cells. Subsequent transplantation of the tumor cells into new mice induced tumor production at the injection site in all the animals within a considerably shorter period of time than that following the initial inoculation. Malignancy of the neoplastic cells was ascertained by histological examination, and the cells were found to have karyotypes of the hamster cells after in vitro cultivation of the tumor cells. These experimental results suggest the transforming potency of the flavoring agents in Chinese hamster cells.

Acrolein↗

Further investigations into the mechanism of the antihypertensive activity of the angiotensin AT1 receptor antagonist, GR138950.

1. The angiotensin AT1 receptor antagonist, GR138950, produces a long-lasting antihypertensive effect in conscious renal artery ligated hypertensive (RALH) rats but this effect does not correlate temporally with its antagonist profile against angiotensin II (AII). In the present experiments we have compared the inhibitory profiles of GR138950 and enalapril, against angiotensin I (AI), with their respective antihypertensive activities. 2. GR138950 (1 mg kg-1, i.a.) and enalapril (3 mg kg-1, i.a.) reduced blood pressure in RALH rats to a similar degree. Maximum reductions in blood pressure occurred approximately 5-24 h and 3-5 h after administration, respectively. The antihypertensive effect of GR138950 lasted for 24-48 h. However, the effect of enalapril lasted for only 5-24 h. 3. In conscious normotensive rats, inhibition of AI-induced pressor responses was maximal 1 h after systemic administration of GR138950 and enalapril. Dose-response curves to AI were displaced to the right, in a parallel manner, 1406 and 102 fold by GR138950 (1 mg kg-1, i.a.) and enalapril (3 mg kg-1 i.a.), respectively. The inhibitory effect of enalapril lasted for < 24 h whereas that of GR138950 lasted for up to 48 h. 4. Contractile responses to AI were extensively inhibited in aortae removed from either RALH rats or normotensive rats, 1 and 5 h after administration of GR138950 (1 mg kg-1, i.a.). Responses were still significantly reduced 24 h after administration but had returned to control levels after 48 h. Enalapril pretreatment (3 mg kg-1, i.a.) did not inhibit contractile responses to AI in aortae isolated from normotensive rats at any time point. 5. These experiments confirm that GR138950 is an effective and long-lasting antihypertensive agent. GR138950 was a more potent and longer lasting antagonist against AI than has previously been found against AII, and the duration of its antihypertensive activity coincides better with its blockade of responses to AI. Blockade of the effects of AII generated locally within the vascular wall might play an important role in the antihypertensive profile of GR138950.

Angiotensin Receptor Antagonists↗

Agent computing themes in biologically inspired models of learning and development.

After evaluating general features and attributes of the agent notion, the overlap of features in candidate (attribute) cores, and several less central features, the paper addresses agent and related theory in neuroscience, observing how agent notions have penetrated portions of this field and how the field itself emphasizes and further develops some agent themes via, e.g. schema theory, neural net-artificial intelligence (AI) comparisons, and other research. In remaining sections, models for development of memory strategies in children are presented, illustrating cooperative and competitive neural modeling agents, an active role for a "human agent in the loop," and integrating broadly-based neural network (NN) modeling with other bio-inspired models.

Aging↗

Infective endocarditis.

Despite improvements in health care, the incidence of infective endocarditis has not decreased over the past decades. This apparent paradox is explained by a progressive evolution in risk factors; while classic predisposing conditions such as rheumatic heart disease have been all but eradicated, new risk factors for infective endocarditis have emerged. These include intravenous drug use, sclerotic valve disease in elderly patients, use of prosthetic valves, and nosocomial disease. Newly identified pathogens, which are difficult to cultivate--eg, Bartonella spp and Tropheryma whipplei--are present in selected individuals, and resistant organisms are challenging conventional antimicrobial therapy. Keeping up with these changes depends on a comprehensive approach, allying understanding of the pathogenesis of disease with the development of new drugs for infective endocarditis. Infection by staphylococci and streptococci is being dissected at the molecular level. New ideas for antimicrobial agents are being developed. These novel insights should help redefine preventive and therapeutic strategies against infective endocarditis.

Anti-Bacterial Agents↗

Shifting paradigms in hormonal therapy for breast cancer.

BACKGROUND: Tamoxifen has been the mainstay of endocrine treatment for postmenopausal patients with early and advanced breast cancer for many years. However, as an anti-estrogen with partial estrogenic effects, tamoxifen also has some serious safety and tolerability issues. Following tamoxifen treatment failure there were initially limited options for subsequent therapy. Therefore, new agents, including new anti-estrogens and aromatase inhibitors (AIs) were developed. METHODS: Data for this review were identified by searches of PubMed and references from relevant articles. Abstracts were included only when the relevant information had not been published in full elsewhere. Only papers published in English were included. RESULTS: The AIs have been shown to be effective treatments for hormone-sensitive metastatic breast cancer. CONCLUSIONS: Current clinical trial data in early breast cancer show longer disease-free survival and time to recurrence with anastrozole than that demonstrated with tamoxifen and very good general tolerability, although longer follow-up is warranted. Clinical trials of the use of AIs in breast cancer prevention and preliminary data for the combination of anastrozole with a gonadotrophin-releasing hormone for the treatment of premenopausal women with early stage breast cancer are also discussed here.

Antineoplastic Agents, Hormonal↗

[The immuno-microbiological characteristics of the small intestine and the translocation of the enteral microflora in acute intestinal obstruction].

The complex examination of 72 patients with acute ileus (AI) of nontumor nature with different severity of endotoxicosis was carried out. The study revealed that AI was accompanied by deep suppression of the immunosecretory and motor evacuatory function of the small intestine, as well as by its pronounced bacterial contamination, mainly due to the significant quantitative prevalence of Gram-negative microflora. The combination of these factors played the key role in the increase of the permeability of the enteric barrier for symbiotic microflora and its massive translocation from the intestinal tract to the internal organs of the body (peritoneal exudate, portal bed), which directly correlated with the severity of endotoxicosis in AI patients. The deficiency of the barrier function of the liver was accompanied by the penetration of infective agents into the general blood stream, thus causing the development of endotoxic shock in AI patients. The analysis of the results thus obtained made it possible to determine the main ways for the elimination of intestinogenic intoxication in AI; they should be aimed at the bacterial decontamination of the small intestine, the restoration of its motor evacuatory and protective barrier functions, the liquidation of portal and systemic bacteremia, the correction of the functional deficiency of the liver.

Acute Disease↗

Arterial injection-digital subtraction angiography.

The authors report on a series of 60 patients who underwent arterial injection-digital subtraction angiography (AI-DSA) for evaluation of suspected cerebrospinal disease. High-quality images were consistently obtained, facilitating accurate diagnosis of a wide variety of traumatic, inflammatory, and neoplastic conditions. As experience has accumulated, the AI-DSA technique has all but supplanted conventional film-screen serialography at this institution. Important advantages of AI-DSA include reduced procedural time and decreased contrast agent burden, which mean increased patient safety. Film costs can also be markedly reduced. Moreover, image quality (information content) is not significantly affected. The technique is especially useful in emergency situations, in cases where multiple arterial injections and serialograms are required, and in cases in which transcatheter embolization is carried out. We feel these considerations will insure broadened application of this diagnostic modality as the AI-DSA equipment becomes more widely available.

Adolescent↗

Problems with the measurement of apolipoproteins AI and AII.

There is considerable evidence demonstrating that increased levels of low density lipoprotein (LDL) cholesterol and decreased levels of high density lipoprotein (HDL) cholesterol are associated with coronary artery disease (CAD). Yet, these lipoprotein markers are insensitive for identifying risk of CAD. Measurement of subcomponents of HDL may offer more sensitive markers. Investigators have focused on protein components (apolipoproteins) of HDL as a potentially important marker. Unfortunately, because much of the immunoreactivity of apolipoproteins is hidden as a result of an association with lipids, it is difficult to measure them accurately. Detergents and other denaturing agents have been used to expose immunoreactivity. Poor correlations among different methods suggest that some detergents presently used may not be adequate for effective measurement of apolipoprotein (APO) AI. Studies using denaturing agents to probe HDL particles indicate that APO AII immunoreactivity is more resistant to exposure than that of APO AI. Data presented here indicate that the immunoreactivity of APO AII can be increased up to 50 percent by treatment with 4M guanidine provided the concentration of guanidine is diluted to less than 50 mM in the assay system. Previous studies failed to notice this effect because high levels of guanidine inhibited the antibody-antigen reaction in the immunoassay, making it appear that APO AII had not been exposed. It is concluded that with our present state of knowledge, it is unclear which, if any apolipoprotein assays, are adequately designed to achieve optimal exposure of antigenic sites, but that pretreatment with guanidine may be a simple, effective way to optimize APO AI and APO AII assays for clinical purposes.

Antigen-Antibody Reactions↗

Role of fulvestrant in sequential hormonal therapy for advanced, hormone receptor-positive breast cancer in postmenopausal women.

The introduction of antiendocrine agents with differing mechanisms of action now mandates the design of rational sequential hormonal regimens for breast cancer. The aromatase inhibitors (AIs), including the nonsteroidal compounds anastrozole and letrozole and the steroidal compound exemestane, are important alternatives or adjuncts to the antiestrogen agent tamoxifen in postmenopausal women with hormone receptor-positive breast cancer in the first-line management of advanced disease and in the adjuvant treatment of early-stage disease. These and other endocrine agents, including the newer estrogen receptor antagonist fulvestrant and also tamoxifen itself, have not been extensively evaluated within the context of hormonal sequencing. Based on a retrospective analysis of data from 3 phase III trials, patients treated with fulvestrant in the first- or second-line hormonal management of advanced breast cancer may derive further clinical benefit from subsequent treatment with an endocrine agent from another class. The need for prospective investigation of post-AI hormonal therapy is intensifying as a result of the increasing clinical use of the AIs. Sophisticated sequencing regimens designed to exploit different mechanisms of action have the potential to confer greater clinical benefit than the historical approach of selecting the agent with the next highest single-agent clinical activity upon disease progression.

Antineoplastic Agents, Hormonal↗

Periodic solutions in a model of competition between plasmid-bearing and plasmid-free organisms in a chemostat with an inhibitor.

We obtain necessary and sufficient conditions on the existence of a unique positive equilibrium point and a set of sufficient conditions on the existence of periodic solutions for a 3-dimensional system which arises from a model of competition between plasmid-bearing and plasmid-free organisms in a chemostat with an inhibitor. Our results improve the corresponding results obtained by Hsu, Luo, and Waltman [1].

Anti-Bacterial Agents↗

[Autologous peripheral blood stem cells mobilization with etoposide plus rhG-CSF versus cyclophosphamide plus rhG-CSF].

BACKGROUND & OBJECTIVE: It is important to get high quality autologous peripheral blood stem cell (APBSC) for successful peripheral blood stem cell transplantation. Cyclophosphamide (CTX) plus recombined human granulocyte colony-stimulating factor (rhG-CSF) is standard regimen for APBSC mobilization. Etoposide plus rhG-CSF is another regimen for mobilization in recent years. The purpose of this study was to observe and compare the effects of these two regimens in APBSC mobilization for the patients with malignant lymphoma and germ cell tumors. METHODS: Fifty-two patients were divided into two groups according to the regimen of mobilization. In CTX group, 26 patients were injected CTX 3.5 g/m(2) intravenously. The other 26 patients in VP-16 group, VP-16 1000 mg/m(2) or 1500 mg/m(2) were given intravenously at random. All patients received rhG-CSF once daily as subcutaneous injection at the dose of 5 microg x kg(-1) x day(-1) from the day of the nadir of white blood cell (WBC) till the day before the last APBSC harvest in both groups. APBSC harvest was performed daily when WBC recovered more than 2.5x10(9)/L in CTX group and 5.0x10(9)/L in VP-16 group. APBSC harvest finished when accumulated mononuclear cells (MNCs) were more than 5x10(8)/kg or CD34(+) cells were more than 2x10(6)/kg. Collected APBSC was infused following condition regimen. Blood parameters, account of harvested cells, the time of hematopoietic reconstitute, and adverse effects were compared between two groups. RESULTS: Following administration of CTX or VP-16, the nadirs of WBC and PLT in CTX group appeared significantly earlier than that in VP-16 group. The doses and times of rhG-CSF administration were not significantly different between the two groups. The start was later and the times of APBSC apheresis were less significantly in VP-16 group. The processed blood volume in single apheresis was more in VP-16 group. Speed and duration of single apheresis were similar in the two groups. Total MNCs were similar in the two groups, but the numbers of MNCs and CD34(+) cells collected in the first harvest and total number of CD34(+) cells collected were significantly more in VP-16 group. With equal quantity infusion of MNCs and CD34(+) cells infusion, hematopoietic reconstitution was achieved in both groups and the time of reconstitution was similar. Nausea and vomiting were more frequent in CTX group. Obvious PLT decrease was observed in VP-16 group. Other adverse effects were similar. CONCLUSION: CTX or VP-16 plus rhG-CSF both were safe and effective regimens for APBSC mobilization. More CD34(+) cells can be harvested by mobilization with VP-16 plus rhG-CSF than mobilization with CTX plus rhG-CSF. And the APBSC mobilized with VP-16 plus rhG-CSF can assure successful hematopoietic reconstitution.

Adolescent↗