Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PADAM stands for partial androgen deficiency in the aging male, and it is currently diagnosed with a testosterone level below 3 ng/ml (300 ng/dl or 12 nmol/l), and with symptoms varying according to the individual. The symptoms are a reduction or even loss of libido, a decline in muscle mass and strength, enhancement of visceral fatty tissue-padding, dryness of the skin, apathy, tiredness and distortion of mood right up to depression, and ostalgia due to osteoporosis. Before starting any form of hormonal substitution, which is only indicated if clinical symptoms and testosterone deficiency correlate, it is absolutely essential to exclude prostate cancer by using clinical evaluation and PSA values. Close PSA monitoring is necessary during testosterone substitution. In more than 95% of all patients with erectile dysfunction, the cause is not testosterone deficiency. Even a decreased level of dehydroepiandrosterone (DHEA) in an elderly male needs no replacement. There is also no indication for estradiol therapy in men--except in the rare case of aromatase deficiency.
 ...
PMID:[PADAM from the urologic viewpoint]. 1104 38

There are two different clinical scenarios in which a decision on hormonal therapy either initially after diagnosis of deferred until the occurrence of signs and symptoms for presently asymptomatic prostate cancer is needed: A more recently described cohort of men with prostate cancer who underwent definitive therapy for putatively curable disease experiencing a rising PSA (biochemical relapse / progression), and a more classical group of men with prostate cancer who were unwilling or unfit to undergo local therapy with curative intent. Long-term hormonal treatment will expose patients to the risk of substantial adverse side effects such as muscle wasting, chronic fatigue, osteoporosis and others, in addition to an overall increase in treatment costs. On the other hand, a potential prolongation of survival and a delay in the development of clinical symptoms may serve as arguments for early treatment. A number of studies have been conducted in which early hormonal treatment delays the time to progression and reduces the cancer-related complication rate such as urinary obstruction and bone fractures. However, results on overall survival remain inconclusive and quality-of-life issues will become more and more important in light of the extended life span of patients with asymptomatic prostate cancer in recent years. Ongoing clinical trials such as EORTC 30991 are needed to provide further information on this important issue.
 ...
PMID:Early versus deferred hormonal treatment for asymptomatic prostate cancer. 1145 13

The aim of this study was to evaluate and clarify the usefulness of different spectral characteristics of myoelectrical activity in the follow-up of development of muscle fatigue. Vastus lateralis (part of quadriceps) muscle loaded in a simple isokinetic exertion test was used as a model. Twelve, well trained athletes served as study subjective to minimize the inter-individual variations. They went through one-minute test with isokinetic device at the range of 90 degrees extension and flexion at the level of their maximal force. The myoelectrical signals were registered from middle of the vastus lateralis muscle by a computerized fast Fourier transform analyzing system based on 80286 and 80287 microprocessors and using surface electrodes. Mean power frequency (MPF) was 65.6 (SE=Standard Error, 1.6) Hz, median frequency (MF) 55.8 Hz and zero crossing rate (ZCR) 92.5 (SE 1.5) during first performance. All these parameters decreased apparently linearly and significantly from the beginning of the test (P<0.001). The decrease rate of ZCR was fastest and MF slowest. The area of power spectrum (PSA) was 1753 (SE 320) units during first performance, and it increased markedly with slightly accelerating rate during the test. In conclusion, for the evaluation of the muscular performance during the development of fatigue it is beneficial to monitor simultaneously MPF, MF and ZCR.
 ...
PMID:Monitoring of muscle fatigue during isokinetic exercise. 1184 Nov 10

Suramin, a polysulphonated napthylurea, has been extensively evaluated over the past 10 years as an anticancer agent, with the most interest in the treatment of prostate cancer. Early clinical results were promising with response rates of up to 70% being reported. However, a recent double-blind study showed only modest palliative effect in patients with androgen independent prostate cancer. In retrospect, it appears those initial reports failed to control for confounding variables such as antiandrogen withdrawal and hydrocortisone. Suramin causes numerous reversible toxicities (lethargy, rash, fatigue, anemia, hyperglycemia, hypocalcemia, coagulopathies, neutropenia, renal and hepatic complications). Neurotoxicity has been the most significant complication and appears to be related to the intensity of the dosing regimen. An optimal therapeutic dose has not been determined, but it is clear that adaptive controls add little benefit. Aside from moderate toxicities and the low therapeutic index in patients with prostate cancer, suramin's development has taught us some valuable lessons (i.e., anti-androgen withdrawal was noted during suramin's development, the use of PSA as an indicator of tumor burden was initiated during the evaluation of suramin). These lessons can be applied to all clinical trials in hormone refractory prostate cancer. Suramin has significantly enhanced the evolution of our knowledge in several areas of prostate cancer biology and treatment.
 ...
PMID:Suramin's development: what did we learn? 1209 81

A phase II trial of vinorelbine and low dose prednisone in hormone-refractory metastatic prostate cancer was conducted in order to investigate its safety, efficacy and impact on quality of life. Vinorelbine was administered at the dose of 25 mg/m(2) i.v. weekly for 12 weeks and then biweekly, along with 10 mg of daily oral prednisone until time of progression. Fourteen patients, median age of 74 years, were treated. The treatment was generally well tolerated with leukopenia and anemia as the major side effects. One patient achieved partial remission and eleven remained with stable disease. One of the eleven patients with stable disease had a dramatic PSA response from 1000 to 236 ng/ml; seven of these progressed after week twelve when vinorelbine was given biweekly. PSA response occurred in 5 of 14 patients. The median time to progression was 28 weeks and the median survival was 17 months. Nine out of the 14 accrued patients were evaluable for quality of life assessment. Five of them improved, three remained unchanged and two had a slight worsening. Four patients had improvement in pain control and fatigue. Our preliminary data suggest that the combination of vinorelbine/prednisone has modest activity in metastatic prostate cancer with a very favorable toxicity profile and is very well tolerated in this group of elderly patients.
 ...
PMID:Phase II study of vinorelbine with low dose prednisone in the treatment of hormone-refractory metastatic prostate cancer. 1279 40

While there are numerous uncertainties surrounding prostate cancer's detection and treatment, more research focusing on the psychological needs of prostate patients is required. This study investigated the support and psychological care needs of men with prostate cancer. Patients were approached during urological oncology clinics and asked to complete the: Support Care Needs Survey (SCNS), Support Care Preferences Questionnaire, EORTC QLQ-C30 (Version 3) Measure plus Prostate Module, and the Hospital Anxiety and Depression Scale (HADS). Of the 249 patients meeting study entry criteria, there was an 89% response rate resulting in a cohort of 210 patients. The data showed that significant unmet need exists across a number of domains in the areas of psychological and health system/information. The more commonly reported needs were 'fears about cancer spreading (44%),' 'concerns about the worries of those close to you (43%),' and 'changes in sexual feelings (41%).' Half of all patients reported some need in the domain of sexuality, especially men younger than 65 years. Needs were being well met in the domain of patient care and support. A significant number of patients reported having used or desiring support services, such as information about their illness, brochures about services and benefits for patients with cancer (55%), a series of talks by staff members about aspects of prostate cancer (44%), and one-on-one counselling (48%). Quality of life (QoL) was most negatively impacted in those who: were < or =65 years old, had been diagnosed within one year, or had metastatic disease. Men < or =65 had decreased social functioning, greater pain, increased sleep disturbance, and were more likely to be uncomfortable about being sexually intimate. Patients recently diagnosed had increased fatigue, more frequent urination, greater disturbance of sleep, and were more likely to have hot flushes. Those with advanced disease scored lower on 12 out of 15 QoL categories. PSA level had no effect on QoL or anxiety/depression scores. Men with advanced disease had greater levels of depression and those < or =65 years old were more likely to be anxious. Although most men with prostate cancer seem to function quite well, a substantial minority report areas of unmet need that may be targets for improving care.
 ...
PMID:Prostate cancer patients' support and psychological care needs: Survey from a non-surgical oncology clinic. 1468 51

To explore the pharmacokinetics and tolerability of AZD2171, an inhibitor of vascular endothelial growth factor receptors 1 and 2, in patients with hormone refractory prostate cancer. Twenty-six patients received oral daily dosing of AZD2171 at 1, 2.5, 5, 10, 20, 30 mg. The maximum tolerated dose (MTD) was defined as the dose below that at which >or=33% of patients experienced a dose-limiting toxicity (DLT) within 21 days of initiating therapy. Pharmacokinetic analysis was performed. DLTs occurred at the 30 mg dose and included grade 3 events in three patients: fatigue (n = 3) and muscle weakness (n = 2). The pharmacokinetic profile revealed an effective half-life of approximately 27 h. At steady state, the unbound drug concentration was 4.4 times above the concentration required to inhibit endothelial cell proliferation in vitro. Four patients experienced PSA reductions within 30 days following drug discontinuation (one on 2.5 mg, two on 20 mg and 1 on 30 mg). In two patients treated with 20 mg, post therapy PSA declines persisted for >17 months, despite a PSA increase on therapy. Resolution of adenopathy occurred in one patient persisting for >17 months. Plasma concentrations were maximum 2-8 h post dosing with an overall median value of 2 h. The dose of 20 mg daily was declared as the MTD. One objective response and several PSA declines following the discontinuation of therapy for toxicity suggest that evidence of clinical efficacy may be delayed. While further study is indicated, careful attention must be paid to the novel toxicities of this agent with prolonged dosing.
 ...
PMID:Phase I dose escalation and pharmacokinetic study of AZD2171, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinase, in patients with hormone refractory prostate cancer (HRPC). 1745 5

Based on the pre-clinical spectrum of activity in taxane-resistant cell lines, we evaluated KOS-862 (epothilone D; 12,13-desoxyepothilone B) as second-line chemotherapy in androgen-independent prostate cancer.Thirty-eight men with metastatic androgen-independent prostate cancer and evidence of progression following docetaxel-based chemotherapy were treated with KOS-862, 100 mg/m(2) (maximum of 240 mg) i.v. weekly for 3 weeks, repeated every 4 weeks. The primary objective for this study was to determine the antitumor activity, measured by PSA decline by more then 50% confirmed 4 weeks later. Two patients (5.3%, 90% CI 1-16%) met criteria for confirmed PSA decline. While both of these patients had previously been treated with docetaxel, neither had confirmed docetaxel-refractory disease. None of the 24 patients with measurable disease had a confirmed partial response. Seventy-three percent of patients had an adverse event leading to dose delay, reduction, or treatment discontinuation. Neurological toxicity and fatigue predominated. Seventeen patients (44.7%) had treatment related grade 3 neurological adverse events including peripheral sensory neuropathy (n = 4, 10.5%), ataxia (n = 3, 7.9%), peripheral motor neuropathy (n = 1, 2.6%), involuntary muscle contractions (n = 1, 2.6%) and neuropathic pain (n = 1, 2.6%). One subject (2.6%) had a grade 4 treatment peripheral motor neuropathy. Further study of this dose and schedule of KOS-862 in this patient population cannot be recommended due to both lack of activity and excessive toxicity.
 ...
PMID:Phase II study of KOS-862 in patients with metastatic androgen independent prostate cancer previously treated with docetaxel. 1761 7

Pertuzumab represents the first in a new class of targeted therapeutics known as HER dimerisation inhibitors. We conducted a phase Ib study to determine the maximum-tolerated dose, the dose limiting toxicities (DLT), and pharmacokinetic (PK) interaction of docetaxel when administered in combination with pertuzumab. Initially, two dose levels of docetaxel (60 and 75 mg m(-2)) were explored in combination with a fixed dose of 1050 mg of pertuzumab; then two dose levels of docetaxel (75 and 100 mg m(-2)) were explored in combination following a fixed dose of 420 mg of pertuzumab with a loading dose of 840 mg. Both drugs were administered intravenously every 3 weeks. The latter dose of pertuzumab was allowed after an amendment to the original protocol when phase II data suggesting no difference in toxicity or activity between the 2 doses became available. Two patients out of two treated at docetaxel 75 mg m(-2) in combination with pertuzumab 1050 mg suffered DLT (grade 3 diarrhoea and grade 4 febrile neutropaenia). Two out of five patients treated at docetaxel 100 mg m(-2) in combination with pertuzumab 420 mg with a loading dose of 840 mg suffered DLT (grade 3 fatigue and grade 4 febrile neutropaenia). Stable disease was observed at four cycles in more than half of the patients treated and a confirmed radiological partial response with a >50% decline in PSA in a patient with hormone refractory prostate cancer were observed. There were no pharmacokinetic drug-drug interactions. The recommended phase II dose of this combination was docetaxel 75 mg m(-2) and 420 mg pertuzumab following a loading dose of 840 mg.
 ...
PMID:A phase Ib study of pertuzumab, a recombinant humanised antibody to HER2, and docetaxel in patients with advanced solid tumours. 1800 Apr 98

We evaluated the efficacy and safety of alpha 1--blocker doxazosin for treatment of lower urinary tract symptoms (LUTS) compatible with benign prostatic hypertrophy (BPH). Fourteen randomized controlled trials enrolled 6261 men, average age 64 years, who had moderately severe LUTS and flow impairment. Compared with baseline measures and placebo effect, doxazosin resulted in a statistically significant improvement in both LUTS and flow. However, when compared with placebo, the average magnitude of symptom improvement (International Prostate Symptom Score [IPSS] improvement < 3 points) typically did not achieve a level detectable by patients. Combined doxazosin and finasteride therapy improved LUTS and reduced the risk of overall clinical progression of BPH compared to each drug separately in men followed over 4 years. Reported mean changes from baseline in the IPSS were -7.4, -6.6, -5.6, and -4.9 points for combination therapy, doxazosin, finasteride, and placebo, respectively. Combination therapy reduced the need for invasive treatment for BPH and the risk of long-term urinary retention. The absolute reductions compared with placebo were less than 4% and primarily seen in men with prostate gland volume > 40 mL or PSA levels > 4 ng/mL. Efficacy was comparable with other alpha 1--blockers. Withdrawals from treatment for any cause were comparable to placebo. Dizziness and fatigue occurred more frequently with doxazosin compared to placebo.
 ...
PMID:Doxazosin in the treatment of benign prostatic hypertrophy: an update. 1804 16


1 2 3 Next >>