Tamoxifen

Sakakibara et al. 1995 ; . The same authors also showed that SULT1B1 had activity towards various thyroid hormone substrates, pNP and dopamine. Since then SULT1B1 enzymes have been isolated from mouse, dog Blanchard et al. 2004 ; and brush-tailed possum Bolton-Grob & McManus, unpublished ; . The human form of SULT1B1 was isolated and characterised by Fujita et al. 1997 ; and shown to be the major thyroid hormone sulfotransferase, having slightly higher affinity for the tri-iodothyronine than SULT1A1. SULT1C SULT1C subfamily members have been isolated from a variety of species including Sult1c1, 1c2 and 1c3 from the rat, 1c1 from the mouse and 1c2 from the rabbit see Blanchard et al. 2004 for references ; . Weinshilboum's group was the first to isolate a human 1C2 cDNA from a fetal liver-spleen cDNA library Her et al. 1997 ; and demonstrate that the gene was located on chromosome 2 at 2q11.2. The identical construct was also cloned and characterized by Yoshinari et al. 1998b ; and Hehonah et al. 1999 ; . Another member of the human 1C subfamily, 1C4, was identified by Sakakibara et al. 1998b ; . To date no endogenous substrates have been identified for members of the IC subfamily. SULT1E The SULT1E enzymes have been widely studied due to their important role in steroid homeostasis. The bovine SULT1E1 was the first cDNA cloned as a known sulfotransferase Nash et al. 1988 ; . Since this initial study, members of the 1E subfamily have been isolated from a number of species including the guinea pig, rat, mouse and pig Blanchard et al. 2004 ; . Aksoy et al. 1994 ; were the first to isolate a SULT1E1 cDNA from a human liver library. The protein encoded by this cDNA was subsequently shown to have high affinity nM range ; for 2 and estrone and a variety of synthetic estrogens, including diethylstilbestrol and tamoxifen Falany et al. 1995; Falany, 1997 ; . While other SULTs such as SULT1A1 and SULT2A1 exhibit high activity towards E2 and estrone, this only occurs at non- physiological 9 and tobradex. Models and, in particular, against prostate cancer xenografts Sedlacek et al. 1996 ; . Many pharmaceutical companies are aiming to develop more selective CDK inhibitors that may prove effective in treating tumours that have developed hormone independence. Apoptosis It has become clear over the last few years that tumour cells, in addition to having deregulated mitogen signalling pathways, have aberrant cell death pathways providing them with a greater chance for survival Fig. 3 ; . Apoptotic mechanisms also play an important role in mediating the response to endocrine therapy since an increase is observed in the number of apoptotic bodies within tumours in patients treated with antioestrogens Ellis et al. 1997 ; and antiandrogens Montironi et al. 1998 ; . A number of oncogenes and tumour suppressor genes such as Bcl-2 and p53 have roles in regulating apoptosis. Bcl-2 appears to protect cells from apoptosis by preventing the release from mitochondria of factors such as cytochrome c that are required to activate destructive caspase proteases Reed 1997, Kroemer et al. 1998 ; . Bcl-2 is overexpressed in a proportion of breast and prostate tumours and may, therefore, be expected to provide a survival advantage. However, an examination of breast cancer patients has demonstrated that the expression of Bcl-2 is tightly associated with ER expression and that those patients with elevated levels of Bcl-2 appeared to benefit most from endocrine therapy Gee et al. 1994, Berardo et al. 1998 ; . Studies in cell culture may provide an explanation for this link since oestrogens stimulate the expression of Bcl-2, possibly as a means to reduce cell death whilst stimulating mitogenesis Teixeira et al. 1995 ; . Moreover, the same authors demonstrate that, in the presence of oestrogen, the MCF-7 breast cancer cell line is more resistant to apoptosis induced by adriamycin than when the ER is antagonised with a pure antioestrogen ICI 164, 384 ; . That this effect is mediated by Bcl-2 is suggested by the observation that the effect of oestrogen can be mimicked by the exogenous expression of Bcl-2. If such in vitro studies translate to the clinic, then they would suggest that cytotoxic drugs administered in combination with tamoxifen to lower Bcl-2 levels could benefit patients. Some studies in prostate cancer have suggested a correlation between the expression of Bcl-2 and poor prognosis Bauer et al. 1996, Matsushima et al. 1997 ; , whereas other studies have suggested no correlation Grossfeld et al. 1998 ; and show that a high level of Bcl2 is associated with early prostate cancer Stattin et al. 1996 ; . Interestingly, androgen-independent prostate tumours express higher levels of Bcl-2 McDonnell et al. 1992 ; and their treatment with hormone ablation therapy increases the level of Bcl-2 Stattin et al. 1996 ; . These observations suggest that Bcl-2 could promote a survival advantage against apoptosis induced by hormone withdrawal. If Bcl-2 promotes cell survival in response to radiotherapy and chemotherapy, then it would be expected that the cancers of patients expressing high levels of Bcl2 would have a poorer response to treatment. There is some evidence that this is true in prostate cancer Huang et al. 1998 ; , where a significantly greater number of tumours from patients who failed radiation therapy expressed Bcl-2. Because the regulation of apoptosis by Bcl-2 is complex, involving the interaction of a number of related proteins which either promote or prevent apoptosis, it is likely that additional proteins are deregulated in endocrine-responsive tumours to reduce the apoptosis threshold. For example, Bax is one family member that antagonises the action of Bcl-2, whose expression is lower in a subset of metastatic breast cancer patients that respond poorly to chemotherapy Krajewski et al. 1995 ; . Antisense therapies directed towards the Bcl2 oncogene are now being evaluated in the clinic in patients with non-Hodgkin lymphoma, a tumour which often contains a t 14; 18 ; translocation involving the Bcl2 gene and increased amounts of the protein Cotter 1997 ; . If successful, it will be interesting to determine whether reducing the level of Bcl-2 in androgen-independent prostate cancer will promote tumour regression, either as stand-alone therapy, or in combination with radiation or chemotherapy. The level of the tumour suppressor protein p53 is stabilised in response to DNA damage Lane & Hall 1997 ; . Since p53 is a transcription factor, its stabilisation enhances the expression of p53-regulated genes. One of the genes regulated by p53 encodes the CDK inhibitor p21 to promote cell cycle arrest Deng et al. 1995 ; . Other genes stimulated by p53 include Bax Miyashita et al. 1994 ; and Fas Owen-Schaub et al. 1995 ; which promote apoptosis. Furthermore, p53 suppresses the expression of Bcl-2 Miyashita et al. 1994 ; thereby further sensitising cells to apoptosis. The p53 gene is frequently mutated in a wide variety of solid tumours, including those of the breast and prostate, and is linked with poor prognosis Gasparini et al. 1998 ; . The loss of p53 or the expression of a dominant negative mutant can prevent apoptosis in response to radiation in a transgenic mouse model Lowe et al. 1993 ; and the loss of functional p53 increases the radioresistance of tumour cell lines McIlwrath et al. 1994 ; . Using immunohistochemistry, it is not clear whether the level of p53 an indication of aberrant p53 function ; predicts clinical response to therapy in primary breast cancer but interesting associations have been made between the presence of particular p53 mutations and the poor response of the tumour to treatment with tamoxifen, radiotherapy or chemotherapy Bergh et al. 1995, Aas et al. 1996 ; . Studies in patients suggest that the level of p53 is elevated in prostate tumours recurring after radiotherapy. What interested us is that the two drugs work in very different ways - tamoxifen primarily by blocking estrogen receptors in tumour cells, anastrozole by suppressing synthesis of estrogen, so that there is less to bind with estrogen receptors and toprol.

INTRAOSSEOUS IO ; ACCESS REGIONAL ALS GUIDELINE Criteria: A. Patient in need of fluid administration for volume expansion or medication administration without IV access. Procedure: A. All Patients: 1. Connect tubing to IO solution container. 2. Fill drip chamber full. 3. Expose IO site: a. Children 3 years: proximal tibia, flat surface b. Children 3 years: proximal tibia or medial malleolus c. Adults: medial malleolus 4. Prepare insertion site scrub with Betadine or alcohol ; . 5. Hold lower leg firmly side-to-side ; against firm surface. B. Children: 1. Angling slightly away from perpendicular, toward the foot, penetrate the skin overlying the flat medial surface of the tibia, 1-2 cm below the tibial tuberosity. Apply firm but controlled pressure with a to-and-fro rotary motion until the tip of the needle passes through the cortex of the bone into the narrow cavity. In some infants, a release of resistance will be felt when this occurs. C. Adults: 1. Locate the medial malleolus. Move 1-2 fingerbreadths anteriorly and locate the flat area of the tibia medial to the tibial crest. Holding the 18 gauge IO needle perpendicular to the site, insert the needle with a twisting motion until decreased resistance of a "pop" if felt. D. All Patients: 1. Remove the stylet and aspirate with a blank syringe. 2. Infuse 1-2 ml NSS through the IO needle and observe for extravasation around the site and on the side of the leg opposite the needle entry site. Proper placement is characterized by: a. Solid anchoring of the needle; b. Minimal resistance to infusion; and c. Lack of extravasation of infused fluid. 3. Attach tubing from IO solution container. 4. Secure the IO needle. 5. Adjust IO rate as desired, and monitor. 6. WARNING: Sternal IO is NOT in scope of practice. Notes: 1. 2. 3. not insert IO needles distal to a fracture site . Avoid inserting through burned tissue. Do not puncture the same bone more than once. Sterile technique should be utilized during IO placement. This technique is best accomplished in children younger than three years, particularly infants. Self-injury has also occurred while performing this procedure. Avoid this by holding the lower limb side-to-side, rather than with one hand underneath the limb, opposite the needle insertion site. 6. All of the complications of peripheral IV lines apply to IO lines, including air and other emboli. 7. Other complications include: a. Osteomyelitis be sure to use sterile technique ; . b. Joint and growth plate damage be sure to angle away from the joint. References kramer, hj, choi, hk, atkinson, k, et al the association between gout and nephrolithiasis in men: the health professionals' follow-up study and trazodone. Regulatory regions within target genes and positively or negatively regulating transcription McDonnell, 1999 ; . Within the confines of this model, it was hard to understand how tamoxifen could manifest SERM activity, since it would predict that compounds were able to function as estrogens and activate or bind to the receptor and competitively inhibit estrogen binding and thus function as antagonists. Clearly, this was an oversimplification of what was occurring in the cell. Indeed, several major discoveries have occurred over the past decade that have revealed additional complexity in ER action and help to explain the pharmacology of SERMs such as tamoxifen. The most important of these are 1 ; the discovery of a second estrogen receptor, ER ; 2 ; the observation that the conformation of the two receptor subtypes is influenced by the nature of the bound ligand; and 3 ; the identification of receptor-associated comodulators, proteins that can enhance coactivators ; or repress co-repressors ; receptor transcriptional activity Beekman et al., 1993; McDonnell et al., 1995; Onate et al., 1995; Kuiper et al., 1996; Mosselman et al., 1996; Brzozowski et al., 1997; Shiau et al., 1998; Pike et al., 1999, 2001; McKenna et al., 1999; McKenna and O'Malley, 2000 ; . All three of these activities have been shown to be important in SERM pharmacology and have been studied in great detail. For a more complete description of these particular advances, the reader is referred to several excellent reviews that have been published recently McKenna et al., 1999; McKenna and O'Malley, 2000 ; . However, the roles that these processes play in determining the agonist antagonist activities of SERMs are highlighted below. V. The Role of ER in SERM Action Exploitation of differential expression of receptor isoforms, or subtypes, is a common mechanism by which tissue-selective drugs can be developed. Thus, with the identification of a second, genetically distinct ER, ER , and the demonstration that its expression pattern was not identical to that of the previously identified receptor ER , a potentially simple explanation for SERM pharmacology was anticipated Kuiper et al., 1997 ; . However, to date, we know very little about the role of ER in estrogen action. mRNA expression studies have demonstrated that ER is expressed in a wide variety of tissues Shughrue et al., 1996; Kuiper et al., 1997 ; . However, confirmation of the existence of significant levels of receptor protein in all mRNA-positive tissues has been more difficult and needs further investigation. Compounding this problem is the difficulty in defining the phenotypes in ER knockouts where no consensus among investigators is yet apparent Couse and Korach, 1999 ; . Studies performed in vitro using reconstituted transcription systems indicate that, on ERE-containing promoters, both ER and ER can activate transcription in response to agonists such as estradiol McInerney et al., 1998; Hall and McDonnell, 1999 ; . With one documented exception, however, it appears as if. The majority of respondents were aged between 30 and 49 61.1% ; . Less than 2% of respondents were aged below 20 or over 70. Table 1.2 Age Age Under 20 20-29 30-39 Over 70 Number 6 88 228 % 0.9 12.6 32.7 and triamterene.

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Sotret.31 spacol i.d. [CARE] .42 spasdel .42 SPIRIVA .63 spironolactone .30 spironolactone hctz .30 sprintec .56 sps 15, 000mg 60m oral susp .53 SPS 250mg ml rectal .53 sronyx .56 ssd, -af .12 stagesic .21 STALEVO.24 stanimax.52 stannous fluoride .52 STARLIX .40 STERILE PADS 2X2 [OTC] .36 STERI-PAD 2X2 [OTC] .36 STRATTERA.24 STROMECTOL .7 SUBOXONE .21 SUBUTEX.21 sucralfate .42 sufenta [INJ] .18 sufentanil citrate [INJ] .18 sulfac .60 sulfacetamide sodium .32, 60 sulfacetamide-prednisolone.59 sulfadiazine.11 sulfamethoxazole trimethoprim .11 sulfamide .60 SULFAMYLON.12 sulfasalazine .43 sulfatol .31 sulfatrim.11 sulfazine, -ec.43 sulfinpyrazone .47 sulindac .47 sultrex .11 supartz [INJ].47 suphera .31 SURE COMFORT [OTC].36 SURMONTIL.25 progesterone cap, sr; cap; sup .58 SUSTIVA .17 SUTENT.16 symax, -sl, -sr[CARE] .42 SYMLIN.41 SYNAREL.58 SYNVISC [INJ] .48 syrex [INJ] .51 SYRINGE [OTC] . 36 T TAMIFLU . 9 tamoxifen citrate . 16 tanacof xr. 62 TARCEVA . 16 TARGRETIN. 16 TASMAR. 24 TAXOTERE [INJ]. 16 TAZORAC . 32 taztia xt . 27 tbc . 34 TE ANATOXAL BERNA. 45 TEGRETOL XR * . 20 terak . 60 terazosin hcl. 30 terbutaline sulfate . 62 terconazole. 13 TERUMO INSULIN SYRINGE [OTC] . 36 tesamone-100 [INJ] . 55 TESLAC . 16 TESTIM. 55 testomar . 64 TESTOPEL [INJ] . 55 testosterone. 55 testosterone cypionate [INJ] . 55 testosterone enanthate [INJ]. 55 testosterone propionate [INJ] . 55 TETANUS DIPHTHERIA TOXOIDS [INJ] . 45 TETANUS TOXOID [INJ] . 45 tetanus toxoid adsorbed [INJ] . 45 TETANUS TOXOID ADSORBED inj . 45 tetcaine. 6 tetracaine hcl . 6 tetracaine hcl [INJ]. 6 tetracycline hcl . 12 tetra-mag . 18 THALOMID. 37 theochron . 63 theophylline anhydrous. 63 THERACYS [INJ]. 16 thermazene. 12 THIOGUANINE . 16 thioridazine hcl [CARE]. 19 thiotepa [INJ]. 16 thiothixene . 19 thrombogen. 52 thyroid. 41 and trimox.
The following classes of anti-estrogenic substances are prohibited: 1. Aromatase inhibitors including, but not limited to, anastrozole, letrozole, aminoglutethimide, exemestane, formestane, testolactone. 2. Selective Estrogen Receptor Modulators SERMs ; including, but not limited to, raloxifene, tamoxifen, toremifene. 3. Other anti-estrogenic substances including, but not limited to, clomiphene, cyclofenil, fulvestrant.
Response at the cellular level may be controlled by only a small subset of genes that determine whether cells proliferate in the presence of this SERM. Consequently, altered expression in tumor cells of only a very few genes may be sufficient to induce cells to proliferate in response to tamoxifen. The ability of tamoxifen to induce numerous genes required to progress through the cell cycle combined with an apparently small number of genes that discriminate between an agonist versus an antagonist response could facilitate the development of tamoxifen-resistant disease. Although tamoxifen largely recapitulated the E2-induced cell cycle gene expression profile, it failed to induce expression of cyclin D1, a key regulator of the G1 S phase transition of the cell cycle. Previous reports have shown that exogenously expressed cyclin D1 is sufficient to induce proliferation as well as activate cdks and phosphorylate protein Rb in MCF-7 and T47D cells 37, 38 ; . Neutralizing antibodies to cyclin D1 blocked E2-stimulated MCF-7 cells in G1 39 ; and treatment with both the pure antiestrogen ICI 182, 780 and tamoxifen down-regulated cyclin D1 expression and inhibited proliferation in mitogen-stimulated breast cancer cells 40, 41 ; . Furthermore, there is a strong correlation between increased levels of cyclin D1 and ER expression in breast cancer 42 ; and it has been recently shown that specific protection again breast cancer is conferred by cyclin D1 ablation 43 ; . Our gene expression studies further establish the importance of cyclin D1 as a mediator of E2-induced cell proliferation and suggest that cyclin D1 may act as a gatekeeper to determine agonism versus antagonism at the cellular level in breast cancer cells. Therefore, the failure of tamoxifen to induce cyclin D1 provides a plausible explanation for the inability of tamoxifen to promote cell proliferation while up-regulating numerous cell cycleassociated genes. Indeed, although tamoxifen failed to induce cyclin D1 expression in tamoxifen-sensitive MCF-7 cells, this gene was constitutively expressed in tamoxifen-resistant cells. The finding that elevated levels of cyclin D1 RNA are associated with a shorter clinical response to tamoxifen could be explained by these observations 44 ; . In addition to cyclin D1, fra-1 was also differentially expressed in MCF-7 cells in response to E2. fra-1 was selectively up-regulated at 4 h of treatment, whereas and triphasil and tamoxifen.
Howell said, is to understand more clearly why ais are superior to tamoxifen in adjuvant treatment and to identify the estrogen receptor cofactors that determine which patients do better on ais versus tamoxifen, and which factors account for the difference between tamoxifen and anastrozole seen in the atac trial. How the drugs work tamoxifen may reduce the risk of breast cancer in high-risk women by almost 50 percent and ultram. In patients whose breast cancer did not recur, more deaths due to stroke were reported in femara treated patients than tamoxifen-treated patients 7 vs 1 ; were cardiac causes 26 vs 13. The relative reduction in breast cancer mortality with anastrozole was 13 percent, and a nonsignificant improvement in time to breast cancer death was demonstrated in atac; however, no statistically significant difference in overall survival was demonstrated between patients receiving anastrozole versus tamoxifen.

Also, in oligospermic males treated with tamoxifen, lh, fsh, testosterone and estrogen levels were elevated. Erectile problems seem to increase with the health problems associated with aging. Therapy and pharmacotherapy treatment reduces reported depressive symptoms compared with an assessment-only condition among out-of-treatment drug injectors and temazepam.

AGE AND BODY MASS INDEX ARE ASSOCIATED WITH THE LEVELS OF TAMOXIFEN METABOLITES Jodi Flaws, Ph.D., Hetal Sheth, M.S., Kate Tkaczuk, M.D., Malcom Danton, Ph.D., Patricia Langenberg, Ph.D., Gwen Lord, Ph.D., and Chang K. Lim, Ph.D. Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine; and MRC Bioanalytical Science Group, University of London jflaws epi.umaryland Currently, most breast cancer patients are treated with 20 mg day of tamoxifen TAM ; for up to five years irrespective of their age, race, or body mass index BMI ; . Although this drug is the predominant adjuvant therapy for breast cancer, about 50% of breast cancer patients do not respond positively to this therapy. That is, they either experience recurrence of their breast tumors, formation of new tumors, or serious side effects while taking TAM. The overall goal of our research is to determine whether the failure of some breast cancer patients to respond positively to TAM therapy is associated with differences in TAM metabolism. The purpose of this specific project was to test the hypothesis that race, BMI, and age are associated with the metabolism of TAM to metabolites known as Ndesmethyltamoxifen N-DMT ; and 4-hydroxytamoxifen 4-OHT ; . To test this hypothesis, 87 breast cancer patients 39 African Americans and 48 Caucasians ; who were taking TAM for at least 30 days prior to enrollment were recruited from a local hospital clinic. Each participant signed an informed consent form, completed a questionnaire, and donated a blood sample. The questionnaires were used to ascertain each patient's race, current BMI, and current age. The blood samples were used to measure each patient's serum levels of TAM, N-DMT, and 4-OHT by quantitative high-performance liquid chromatography mass spectrometry. The results indicate that serum levels of TAM, N-DMT, and 4-OHT differed between breast cancer patients. TAM levels ranged from 1-124 ng ml mean standard error 62.2 4.0 ng ml ; , N-DMT levels ranged from 1-150 ng ml 60.9 5.2 ng ml ; , and 4-OHT levels ranged from 1-11 ng ml 4.8 0.6 ng ml ; . The results also indicate that BMI was significantly associated with 4-OHT levels and that age was significantly associated with NDMT levels p 0.05 ; . Women with a BMI 30 kg m2 had 5.5 0.8 ng ml, while women with a BMI 30 kg m2 only had 2.8 1.1 ng ml of 4-OHT p 0.05 ; . Women who were 58 years had 69.3 8.4 ng ml, while women who were 58 years only had 46.2 7.7 ng ml of N-DMT p 0.05 ; . These associations remained significant after adjusting for potential confounders in regression models. Collectively, these data suggest that BMI and age are associated with serum levels of TAM metabolites. Thus, these factors should be taken into consideration when prescribing TAM therapy for breast cancer patients.
Exemestane is licensed for the treatment of advanced breast cancer in ER + women with natural or induced postmenopausal status whose disease has progressed following antioestrogen therapy. Tolerability profile of ARI: Generally well tolerated. Nausea and vomiting, musculoskeletal disorders and fractures have been reported to be more common in ARIs compared to tamoxifen 3 ; . Less common symptoms are hot flushes, vaginal bleeding, thromboembolic events and endometrial cancer Dosage schedule Anastrazole dosage: 1mg orally daily Letrozole dosage: 2.5mg orally daily Exemestane: 25mg daily Ovarian suppression Three main methods of ovarian suppression OS ; are Luteinising hormone-releasing hormone LH-RH ; analogues, surgery and radiotherapy. Tolerability profiles Side-effects of Surgery include wound complication, adhesions, DVT and anaesthetic problems Radiotherapy includes uncertain menopausal effects requiring follow-up with hormone levels. LH-RH analogue include reduction in bone mineral density and natural menopause symptoms hot flushes, mood changes ; . Luteinising hormone-releasing hormone LH-RH ; agonists: Goserelin only licensed for use in breast cancer and is only indicated in ER + premenopausal patients. Dosage schedule Goserelin 3.6mg ; is given monthly as a subcutaneous injection for a minimum of 2 years. Note: The 3 monthly depot preparation 10.8mg goserelin ; must not be used for this purpose. Principles that govern this protocol are.

Been seen with the use of toremifene though far less patients have been treated with toremifene than with tamoxifen 147 ; . Raloxifene has not been associated with an increased rate of endometrial carcinoma compared with placebo 108, 148 ; . Anastrozole, an aromatase inhibitor with the longest adjuvant tolerability data, does not seem to increase the risk of endometrial cancer 121 ; . In general, gynecologic symptoms such as vaginal bleeding 86, 121 ; and discharge 121 ; are more common with tamoxifen than with aromatase inhibitor use. The effects of endocrine therapies on bone and lipid metabolism are discussed in more detail in chapters 6 and 8. Letrozole is also well tolerated, causes a marked decrease in serum and urine estrogen levels, and has little effect on other endocrine factors. In clinical trials with postmenopausal women, plasma levels of androgens were unchanged with letrozole treatment, and increases in LH, FSH, and SHBG were detected over time 139 ; . A multicenter, randomized, double-blind study in advanced breast cancer reported letrozole more effective than tamoxifen in response rate, clinical benefit, time to progression, and time to treatment failure 140 ; . Letrozole at the recommended therapeutic dose of 2.5 mg once daily effectively suppressed total-body aromatization, with a mean percentage inhibition of greater than 99.1%, and suppressed plasma estrone and estradiol levels by 84 88% in postmenopausal women with metastatic breast cancer 141 ; . 3. Exemestane. Exemestane Aromasin; Pfizer, New York, NY ; is a potent steroidal inhibitor of human placental aromatase, and a single oral dose of 25 mg exemestane was found to cause a long-lasting reduction in plasma and urinary estrogen levels. Maximal suppression of circulating estrogens occurred 23 d after dosing and persisted for 4 5 d 142 ; . The lengthy duration of estrogen suppression is thought to be related to the irreversible nature of the drug-enzyme interaction rather than pharmacokinetic properties of the compound. Exemestane is also well tolerated, causes a marked decrease in serum and urine estrogen levels, and has no effect on other endocrine factors 142146 ; . Increased doses of exemestane can lead to suppression of SHBG 147, 148 ; . Exemestane was shown to inhibit peripheral aromatase by 97 98% 144, ; . Table 1 compares the inhibitory activities in vitro and in vivo of aromatase inhibitors that have been evaluated clinically. As described earlier, anastrozole and letrozole are both nonsteroidal competitive inhibitors of aromatase, whereas exemestane is a mechanism-based inhibitor. Investigations of these therapeutic agents in cell lines expressing high levels of aromatase, such as JEG-3 and JAr choriocarcinoma cells, have examined the impact of these inhibition characteristics on the residual in vitro aromatase activity and protein levels. Several mechanism-based aromatase inhibitors produce prolonged suppression of aromatase catalytic activity for up to 48 cells following short drug exposure 72, 94, 150 ; . On. Other causes. The curves are similar, but the prostate trials have statistical noise from the large numbers of deaths that are unrelated to prostate cancer or its treatment. When patients are older, deaths from other causes confuse trial results. The problem with evaluating hormone therapy for prostate cancer is that only a few thousand men with prostate cancer were being randomly assigned to therapy, compared to tens of thousands of women with breast cancer. That is why the evidence of benefit in breast cancer is so much better. In breast cancer, we have seen impressive decreases in death rates in middleaged women as a result of early use of tamoxifen and chemotherapy. I believe the effects of earlier treatment with hormonal therapy in prostate cancer over the next five or 10 years will be comparable to those produced by tamoxifen in breast cancer.
Them, in the event that questions arise during the timeline process that the researchers did not think to include in their notes. See Appendix 1. ; The Role of the Facilitator During the Process The facilitator bears responsibility for several aspects of the process. First, she must recognize that the telling of the story is only one small piece of the puzzle. She must prime the group in attendance, initially, so that they can fully participate in the analysis of the information being presented. Each participant should be helped to feel safe, welcome to participate, and acknowledged in a valued role. This is especially true for family members and direct care staff, who very often feel outnumbered and devalued during team meeting experiences. It must be made clear that the timeline tool, in the long run, will only be effective if the people who support the person the subject of the biography ; are fully involved, engaged and invested in the process. The facilitator must keep part of her awareness focused on the level of participation going on in the group, during the entire process. Secondly, the facilitator must see that pertinent facts are listed on the charted timeline and that once listed, the relevance of the information is explored with the group. "Why is this important? What ramifications might this have for this person? What life lessons might the individual have learned?" Periodically, the facilitator stops the action to have the group assess the person's development to date. "How does this person's life experiences match those of typical contemporaries? What opportunities did the person have to feel loved, admired and respected? To develop praise-worthy skills? To explore independence through the context of interdependence?" The facilitator also continues to emphasize that everyone is engaging in "respectful guessing" as they try to make sense of past events and develop a rich approach to supporting the person in the context of the person's life story. While the facilitator should have a good understanding of typical developmental processes, as well as experience with positive approaches and a fundamental knowledge of mental health issues in individuals with mental retardation, it is not expected that he or she be an expert in all areas of practice. Instead, the facilitator will be expected to draw on the expertise of the team members, including asking for more team supports when preliminary research indicates that some additional expertise might be important, such as the presence of a nurse, a psychologist, or an occupational therapist who is trained in sensory integration. We have, of course, found it very helpful when we could have a physician or a psychiatrist as part of the team as we go through the biographical timeline process. The facilitator works with the team, to highlight key issues that present themselves during the process, and to help the team look at the impact of these issues on the current challenges that the person presents. The issues are then explored with the group in the context of unmet needs and mechanisms that the team could employ.
KAREN MAGINNIS, ACCENTHEALTH HOST: HELLO, I'M KAREN MAGINNIS AND YOU'RE WATCHING ACCENTHEALTH. HOT FLASHES CAN BE UNCOMFORTABLE AND DISRUPTIVE, BUT THEY DON'T ONLY AFFECT WOMEN WHO ARE EXPERIENCING MENOPAUSE. THEY CAN BE A SIDE EFFECT FROM A DRUG COMMONLY USED TO TREAT BREAST CANCER. CNN'S RHONDA ROWLAND REPORTS MORE ON HOT FLASHES AND HOW RESEARCHERS HAVE UNCOVERED A SURPRISING NEW TREATMENT OPTION. RHONDA ROWLAND, ACCENTHEALTH REPORTER: 33-YEAR-OLD MICHELLE TENNYSON HAS BATTLED BREAST CANCER FOR TWO YEARS, AND AN UNEXPECTED SIDE EFFECT HOT FLASHES. MICHELLE TENNYSON, BREAST CANCER PATIENT: You lose your concentration. Things that you try to accomplish it's very difficult to continue until the hot flash has subsided. ROWLAND: THEY CAN EVEN WAKE YOU IN MICHELLE'S CASE, UP TO 8 TIMES A NIGHT. TENNYSON: When you don't have enough energy to go and do the things that you want to do, it's very disruptive and very frustrating. ROWLAND: CHEMOTHERAPY CAN PUT BREAST CANCER PATIENTS INTO PREMATURE MENOPAUSE DUE TO ITS EFFECT ON THE OVARIES. TAMOXIFEN, THE ANTI-ESTROGEN DRUG, ALSO CAUSES HOT FLASHES. ESTROGEN REPLACEMENT THERAPY IS A PROVEN REMEDY FOR HOT FLASHES BUT IT MAY INCREASE THE RISK OF BREAST CANCER. DR. CHARLES LOPRINZI, MAYO CLINIC: Patients don't want to take it and physicians don't want to give it primarily because of concern about what estrogen will do on breast cancer. ROWLAND: NOW A SURPRISE DOCTORS HAVE SEEN RELIEF FROM HOT FLASHES IN A CLASS OF ANTIDEPRESSANTS KNOWN AS SSRI'S PROZAC, ZOLOFT, PAXIL. MICHELLE IS ONE OF THIRTY WOMEN WHO PARTICIPATED IN A PILOT STUDY OF PAXIL. TENNYSON: I started feeling the effects almost immediately I would say 3, 4 days tops my hot flashes started lessening. DR. VERED STEARNS, LOMBARDI CANCER CENTER, GEORGETOWN UNIVERSITY: The women also reported improvement in depression scores and sleep. The sleep scores have improved significantly as well as quality of life. ROWLAND: IN THE LARGEST STUDY TO DATE, RESEARCHERS FOUND A SIMILAR DRUG VENLAFAXINE, OR EFFEXOR TAKEN AT LOW DOSES REDUCED HOT FLASHES BY 60 PERCENT. NEGATIVE SIDE EFFECTS WERE MINIMAL. AND THERE WAS AN UNANTICIPATED POSITIVE SIDE EFFECT. LOPRINZI: And lo and behold, the libido was improved in all the women in the study whether they were on placebo or the venlafaxine and there was a tendency for an improvement more with the people on active drug. ROWLAND: THERE'S ALSO EVIDENCE THAT ANTIDEPRESSANTS RELIEVE HOT FLASHES IN MEN BEING TREATED FOR PROSTATE CANCER. NOW THAT MICHELLE TENNYSON IS NO LONGER PLAGUED BY HOT FLASHES FOR THE FIRST TIME IN TWO YEARS, SHE'S CONSIDERING A RETURN TO HER CAREER AS A FLIGHT ATTENDANT. TENNYSON: As they improve, I just get more energy. I feel like I can go out and do some things that I want to do and enjoy my life. ROWLAND: SO FAR STUDIES HAVE BEEN DONE PRIMARILY IN WOMEN WHO HAVE SURVIVED BREAST CANCER, BUT DOCTORS SAY HEALTHY WOMEN CONCERNED ABOUT BREAST CANCER CAN ALSO GET RELIEF FROM HOT FLASHES WITH ANTI-DEPRESSANTS. RHONDA ROWLAND, CNN, ATLANTA. MAGINNIS: WHETHER THE RESULT OF BREAST CANCER TREATMENT OR THE NORMAL ONSET OF MENOPAUSE, IF THE DISCOMFORT OF HOT FLASHES IS DISRUPTING YOUR LIFE, TALK WITH YOUR DOCTOR ABOUT POSSIBLE TREATMENT OPTIONS.

Quality mental health care starts with an in-depth evaluation.