Rat isolated heart model
Female Wistar rats (180–200g; total of 52) were anaesthetized with pentobarbital sodium (60mgkg−1 i.p.), and hearts were excised, mounted on a Langendorff apparatus and perfused in a constant pressure mode with modified Krebs–Henseleit bicarbonate buffer containing (mM) 118.5 NaCl, 24.8 NaHCO3, 4.7 KCl, 1.2 MgSO4, 1.2 KH2PO4, 2.5 CaCl2 and 10 glucose. A suture was passed around a major branch of the left coronary artery. After equilibration, hearts were subjected to 30min of regional ischemia by occluding the snared artery followed by 2h of reperfusion as depicted in Figure 1. Control hearts were subjected to only 30min of regional ischemia and then reperfusion. Four groups of hearts were treated with different vardenafil dosages (1, 10, 100 and 1000nM) during the reperfusion period starting 5min before reperfusion. In the next groups, one of three inhibitors was co-infused along with the protective vardenafil dose of 10nM. These inhibitors included the GC inhibitor ODQ (10μM) and the PKG inhibitor KT-5823 (1μM). Finally, three groups of hearts were treated with only ODQ or KT-5823, as noted above, to exclude independent effects of the blockers.
News - Part 33
Rat isolated heart model
Recent studies have implicated that PDE-5 inhibitors, such as sildenafil, vardenafil or tadalafil, induce preconditioning-like effects in the heart and protect against ischemia/reperfusion injury. PDE-5 inhibition has been shown to enhance the accumulation of the cyclic nucleotide cGMP, which in turn acts as a second messenger in many signaling events in healthy and diseased myocardium. Intracardiac cGMP is produced by two isoforms of GC: particulate GC, which is activated by natriuretic peptides (atrial, brain and C-type natriuretic peptides) and soluble GC, which is activated by nitric oxide. On GC activation, cGMP accumulates and interacts with several targets, including the cGMP-dependent PKG. The cGMP/PKG pathway has been shown in many reports to be involved in the protective signaling of preconditioning, for example, direct PKG activation with a cell-permeant cGMP analogue proved to be protective, as well as receptor-mediated preconditioning could be blocked with the GC inhibitor 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ). Therefore, it seems only logical that PDE-5 inhibitors would protect the heart against ischemia/reperfusion injury when administered before ischemia. A detailed summary of the attenuation of increased cGMP during ischemia/reperfusion can be found in a recent review from Burley et al. Although there is increasing evidence that the heart is protected against ischemia/reperfusion injury due to elevated cGMP or PKG activity, considerably less is known whether this is exclusively related to myocytes or other compartments (for example, endothelium) play a partial or even major role.
The efficacy of phosphodiesterase type 5 (PDE5) inhibitors in restoring erectile function in men with erectile dysfunction (ED) has been evaluated primarily by means of patient-reported outcome measures, including questionnaires and performance scoring.
IMPROVING TREATMENT OUTCOMES IN PROSTATE CANCER PATIENTS WITH A LOW SOCIOECONOMIC STATUS: HOW CAN NURSES HELP?
Pretreatment Education and Counseling
As part of the counseling of men diagnosed with prostate cancer, healthcare practitioners (physicians, practice nurses and health educators/navigators) need to provide good information about the relative benefits and risks of the treatments advocated, including their likely influence on subsequent QOL, and then incorporate patient preferences into the therapeutic decision. In doing so, it should be appreciated that whereas some patients will want to maximize their chances for a “cure” and will accept the risk of post-treatment complications, such as urinary and sexual dysfunction, others will opt for a higher risk of prostate cancer recurrences to retain their present urinary and sexual function. It also needs to be realized that patients may receive conflicting information about the benefits and risks of treatment from different sources and that there may be considerable uncertainty regarding cure rates, the likelihood of complications occurring and the degree to which their lives will be affected by these complications. Although it might be assumed that a patient’s treatment decision will be based on a rational assessment of the available information, this may not be the case as his interpretation of potential outcomes may be based on the personal context of a particular complication.
Influence of Socioeconomic Status, Literacy and Educational Levels on the Diagnosis and Treatment of Prostate Cancer
Although earlier studies (reviewed in Haas and Sakr) of the association between socioeconomic status and prostate cancer incidence reported inconsistent findings, a more recent epidemiological study has suggested that the advent of widespread PSA testing in the United States has changed the relationship, due largely to the greater use of PSA screening among men of higher socioeconomic status. Analysis of the relationship between socioeconomic status (defined by income and educational attainment) and prostate cancer incidence during the period 1972-1997 indicated no relationship in any racial or ethnic group prior to 1987; after this time, however, a strongly positive relationship was found for all racial/ethnic populations except Asians. Men of higher socioeconomic status were diagnosed with localized disease more frequently but with distant (metastatic) disease less frequently than men of low socioeconomic status.23 Other studies have indicated that stage at diagnosis is inversely correlated with health insurance status among African Americans, in that only 50% of those with distant disease had health insurance as compared with 100% of those with localized disease,24 and that men with Medicare only or no health insurance have a worse health-related QOL over time following treatment of prostate cancer than those with HMO insurance. canadian prescription drugs
These findings suggest that men of lower socioeconomic status and with poorer health insurance coverage for prostate cancer screening services are diagnosed and treated later and, hence, have worse outcomes. However, where access to healthcare is equivalent among men of different socioeconomic status, as in the U.S. military, no association between socioeconomic status and either the stage of the disease at diagnosis or five-year survival is observed. healthcare pharmacy
Low literacy may also be a significant barrier to the diagnosis of early-stage prostate cancer. This has important influences on the complex interaction between patients and physicians and on patients’
understanding of the recommended treatments and, ultimately, their decision-making process. Data from the CaPSURE program have suggested that educational level is predictive of the primary treatment received by US. patients with newly diagnosed prostate cancer. Those with a lower educational level exhibited higher usage of primary hormonal therapy and decreased rates of radical prostatectomy compared with those who have a higher education level, and this was evident in both African Americans and whites (Figure l). However, among older men (>75 years of age), those with higher educational levels received more radiotherapy and less primary hormonal therapy than those with lower educational levels, suggesting that the impact of education on primary treatment is different depending on patient age. canadian antibiotics
Other CaPSURE data have shown that among men for whom “watchful waiting” was the initial management, educational level was among the factors (others included age, PSA level and Gleason grade) predicting eventual active treatment. Men with a low educational level were less likely to receive active treatments than those with higher levels of education. However, in predicting primary treatment, educational level appears to be less influential than clinical variables such as stage, grade and pretreatment symptoms. Clinical factors have such a strong influence on the physician’s decision that the patient’s educational level may become less important in determining what treatment is recommended and what the patient ultimately receives. Canadian Pharmacy mall
Management of prostate cancer is complex and subject to numerous clinical, scientific, demographic and economic dynamics, which give rise to constantly changing practices. Recent advances in therapy have reduced the incidence of some untoward effects, and patients can now be offered a range of treatments (Table 2) depending on their age, tumor stage (TNM classification; Table 3) and grade (Gleason score), and the presence or absence of comorbidities. In the United States, guidelines developed by the National Comprehensive Cancer Network (NCCN) provide recommendations for the appropriate use of both observation-only (appropriate for patients with a limited life expectancy or with low-risk cancers) and active interventions. Following an initial assessment and staging evaluation, the NCCN guidelines advocate either “watchful waiting” (expectant management), radiotherapy, radical prostatectomy with or without lymph node dissection, hormonal therapy or combinations of these treatments depending on the patient’s degree of risk and life expectancy. Whichever form of therapy is selected, patients should be monitored periodically via PSA tests, digital rectal examinations (DREs) and bone scans. In those who exhibit increasing PSA levels after prostatectomy, salvage therapy with radiation, chemohormonal therapy or hormonal therapy alone should be considered, while surgery (prostatectomy or cryosurgery) should be considered for those whose PSA levels rise after radiotherapy. order Revatio online
Increasingly, prostate cancer is being diagnosed with low-risk clinical characteristics, and the available evidence indicates a decrease in mortality with treatment of early-stage disease. Data from the Cancer of the Prostate Strategic Urologic Research (CaPSURE) program, which reflects a mix of locales and practice types, indicate that U.S. patients have become less likely to pursue “watchful waiting” in recent years and are more likely to receive brachytherapy or hormonal therapy. Since the advent of widespread PSA testing in the late 1980s, the percentage of low-risk patients being managed with “watchful waiting” has decreased by more than half, from 20% in 1993-1995 to 8% in 1999-2001. Over the same period, the use of both external beam radiotherapy and radical prostatectomy also decreased from 13% to 7% and 55% to 52%, respectively, while that of brachytherapy and primary hormonal therapy increased significantly from 4% to 22% and 7% to 12%, respectively. The explanation for these trends in primary management strategies is likely to involve a number of clinical, psychological, medicolegal and economic factors. canadian drugs
In this regard, changes in therapy costs and patients’ expectations of the QOL benefits may be significant factors. Costs for individual patients include both the direct costs of treatment (including those arising from the management of posttreatment complications) and indirect costs such as travel to clinic appointments and missed workdays. The direct costs of initial therapy for localized prostate cancer are highly dependent on the treatment received, and they have been found to increase with higher-stage disease due to increased inpatient resource use and greater use of adjuvant hormonal therapy. However, initial treatment costs decrease with increasing age at diagnosis, probably reflecting greater use of “watchful waiting” in older men. Data from the CaPSURE database have indicated that first-year costs for treating prostate cancer in the United States (based upon 1996 Medicare payment schedules) were $6,810 for stage-T2c disease, $6,426 for stage-T2a/b disease and $5,731 for stage-Tic disease. Although first-year costs for radical prostatectomy and external-beam radiotherapy were similar ($7,320 and $7,430, respectively), they were considerably lower for patients followed with “watchful waiting” ($484) and much higher for those who received neoadjuvant androgen ablative therapy followed by radical prostatectomy or radiotherapy ($12,223). depressant drugs
Figure 1. Treatment distribution according to educational level in: (a) 3,027 white men; and (b) 332 African-American men who were diagnosed with prostate cancer between 1992 and 2001
In addition to cost, projected QOL outcomes can also be an important treatment selection criterion in individual patients. QOL endpoints need to be assessed separately from clinical endpoints such as disease-free survival. Patients’ perceptions of their posttreatment QOL—notably their urinary, bowel and sexual function after procedures such as radical prostatectomy, radiotherapy and androgen ablative therapy (Table 2)—may bias their viewpoint of the treatment options available to them in a different direction to that of the physician. Consequently, QOL dimensions such as functional status, sexuality, micturition, pain, fatigue, social activity and psy chological well-being—all of which can be measured via QOL instruments/questionnaires—need to be considered by physicians when discussing treatment options with patients, particularly as the patient may be less optimistic about the outcome than the physician suspects. impotence pills
Management of patients with prostate cancer may include “watchful waiting,” hormonal (androgen ablative) therapy, radical prostatectomy, cryosurgery, chemotherapy or radiation therapy in the form of external-beam radiotherapy, high-dose radiotherapy or brachytherapy. While clinical variables, such as age, disease stage, prostate-specific antigen (PSA) level, Gleason score, comorbidities and symptoms, are important considerations in the physicians’ selection of treatment(s), patient participation in the decision-making process is desirable and generally encouraged. Therefore, provision of adequate information to patients is vital as they need to understand the benefits and risks of the treatment alternatives, the costs and follow-up procedures involved, and the likely survival and quality-of-life (QOL) outcomes. canadian antibiotics
Data to indicate a clear superiority of one treatment choice over another are, however, lacking, and this uncertainty can affect the decision-making process—particularly when patients are faced with several options. In addition to clinical variables, numerous other factors may influence an individual patient’s decision concerning treatment, including income, insurance status, educational level, ethnicity, personality, lifestyle, philosophy/beliefs, previous life experiences and current health status. The interrelationships between these clinical and social variables can be very complex. An important consideration in patients’ participation in the decision-making process is how they access information and use it. This may not be fully appreciated by physicians, as information sources—ranging from the electronic media and specific literature to advice from friends—can vary widely in the way the benefits and risks of the various treatment options are portrayed. In addition, there may be limitations to physicians’ understanding of patient outcome preferences, which can adversely affect the patient-physician relationship. canadian pharmacy online
Socioeconomic status, literacy and educational levels have important implications for patients’ access to healthcare, ability to manage the bureaucracy of medical insurance and healthcare institutions, ability to attend clinics for follow-up visits, and their understanding of information provided to them on prostate cancer and its treatment. Lack of health insurance by many Americans is a major barrier to receipt of optimal healthcare; about 16% <65 years of age have no insurance coverage, while one-third of people ^65 years of age have Medicare coverage only. In 2002, 18% of Americans aged 18-64 years reported having no regular source of healthcare, and for 6% cost had been a barrier to obtaining needed healthcare during the previous year. Percentages of the population among the various racial and ethnic groups of the U.S. population who have no healthcare coverage or no regular source of medical care are shown in Table 1 (American Cancer Society statistics). generic sildenafil citrate
This article outlines the treatment options for patients with newly diagnosed prostate cancer and discusses how a low socioeconomic status and educational level can adversely influence therapeutic decision-making and, consequently, satisfaction with treatment outcomes. It also discusses measures designed to increase patients’ informed participation in the shared decision-making process and to enhance their posttreatment QOL. Cefdinir antibiotics