Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcitriol acts synergistically with carboplatin in preclinical models of adenocarcinoma of the prostate. The authors sought to test high-dose oral calcitriol in combination with carboplatin in patients with metastatic androgen-independent prostate cancer. Seventeen patients received oral calcitriol (0.5 microg/kg) on day 1 and intravenous carboplatin (AUC 7 or AUC 6 in patients with prior radiation) on day 2, repeated every 4 weeks. PSA response was the primary end point and was defined as a 50% reduction confirmed 4 weeks later. Palliative response (2-point reduction or normalization of pain on the present pain intensity [PPI] scale without increased analgesic consumption) was also examined. One of 17 patients (6%, 95% CI, 0-28) achieved a confirmed PSA response. Four patients (24%, 95% CI, 7-49) had PSA reductions ranging from 24 to 38%. Of the 15 patients with a PPI > or = 1 point on entry, 3 (18%, 95% CI, 4-48) met criteria for palliative response. Treatment-related toxicity was mild and generally similar to that expected with single-agent carboplatin. Despite encouraging preclinical evidence, the addition of oral calcitriol to carboplatin in this study was not associated with an increase in the response rate when compared with the reported activity of carboplatin alone.
 ...
PMID:High-dose calcitriol and carboplatin in metastatic androgen-independent prostate cancer. 1559 26

Plasma concentrations and tolerability of a novel somatostatin analogue sms-D70 were studied in patients with metastatic hormone-resistant prostate cancer (HRPC) or metastatic renal cell cancer. To overcome the limitations of the octapeptides having affinity only to somatostatin receptor subtypes 2 and 5, HRPC expressing mainly somatostatin receptors 1 and 4, a somatostatin derivative based on the natural somatostatin having affinity to all five somatostatin receptor subtypes, was developed. The in vivo stability of this dextran-conjugated derivative, somatostatin-D70, was confirmed previously in animal studies, and the nanomolar "panaffinity" has been shown in in vitro receptor binding studies on cell lines transfected with the somatostatin receptor genes. Sms-D70 was given with subcutaneous injection once a week at dose levels of 5, 10, 20, 35, and 50 mg. For pharmacokinetic studies, sms-D70 was labeled with 131I. Fourteen patients were treated, of whom 10 had prostate and 4 renal cell cancer. The kinetic data revealed high stability with a long half-life in the blood. The drug was well tolerated, and no grade 4 (WHO) toxicity was observed. The maximal tolerated dose could not be established due to the lack of dose-limiting toxicities. Objective PSA responses were not recorded in these heavily treated patients, but subjective stabilization of pain was observed and urinary symptoms were alleviated in four patients. Three patients with metastatic HRPC received 5-10-mg intravenous injections of sms-D70 once weekly for 4-14 months on a compassionate use basis. In all cases, serum PSA values decreased more than 50% from the pretreatment level, but these results are difficult to interpret due to concomitant treatments given to these patients. In conclusion, sms-D70 was well tolerated in the treatment of metastatic prostate and renal cell cancer, but no responses were found in these heavily treated patients.
 ...
PMID:Phase I trial on sms-D70 somatostatin analogue in advanced prostate and renal cell cancer. 1565 Feb 61

Biochemical parameters and pathological features as well as biopsy related morbidity of prostate cancer detected on second, third and fourth repeat prostate biopsy in men with a serum total PSA level between 4 ng/mL and 10 ng/mL were evaluated and compared to those cancers detected on initial prostate biopsy. In a prospective European Prostate Cancer Detection study, 1051 men with a total PSA level between 4 ng/mL and 10 ng/mL underwent transrectal ultrasound (TRUS)-guided sextant biopsy and two additional transition zone biopsies. All subjects whose biopsy samples were negative for prostate cancer (CaP) underwent a first repeat biopsy after 6 weeks. If also negative a third and even a fourth biopsy was performed at 8 weeks intervals. Those with clinically localized cancers underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either initial or repeat biopsy and clinically organ confined disease who agreed to undergo radical prostatectomy were compared. Cancer detection rates on first, second, third and fourth biopsy were 22% (231/1051), 10% (83/820), 5% (36/737) and 4% (4/94), respectively. Percent free PSA and PSA-TZ were the most powerful parameters to predict cancer on repeat biopsy. Overall, of patients with clinically localized disease (67% of cancers detected), 86% underwent radical prostatectomy and 14% opted for watchful waiting or radiation therapy. Overall, 58.0%, 60.9%, 86.3% and 100% had organ confined disease on first, repeat, third and fourth biopsy, respectively. Despite statistical significant differences with respect to multifocality (p=0.009) and cancer location (p=0.001) (cancers on second biopsy showing a lower rate of multifocality and a more apico-dorsal location), there were no differences with respect to stage (p=0.2), Gleason score (p=0.3), percentage Gleason grade 4/5 (p=0.2), serum PSA and patient age between first and second biopsy. However, cancers detected on third and fourth biopsy had a significantly lower Gleason score (p=0.001 and 0.001), lower rate of grade 4/5 cancer (p=0.02), lower cancer volume (p= 0.001 and 0.001) and lower stage (p= 0.001). Morbidity of first and repeat biopsy were similar, whereas third and fourth biopsy had a slightly higher complication rate. Interestingly, patients under 60 years of age reported a higher pain apprehension as quantified with the visual analog pain scale (VAS). Further, the use of the Vienna tables allowed an accurate calculation of the number of biopsy cores required based on prostate volume and age. Despite differences in location and multifocality, pathological and biochemical features of cancers detected on initial and second biopsy were similar, suggesting similar biological behavior. Cancers detected on third and fourth biopsy had a lower grade, stage and cancer volume as compared to cancers on first and repeat biopsy. Morbidity of first and repeat biopsy were similar, whereas third and fourth biopsy had a slightly higher complication rate. Hence, a second prostate biopsy in all cases of a negative finding on initial biopsy appears justified. Third and fourth repeat biopsies however, should only be obtained in very selected patients with high suspicion of cancer and/or poor prognostic factors on the first or second biopsy. Power Doppler TRUS will further enhance prostate cancer detection as will artificial neural networks as patient selecting tools.
 ...
PMID:Prostate biopsy: who, how and when. An update. 1578 Jan 65

Procedural sedation and analgesia has become a commonplace procedure in the ED, certainly falling under the domain of the EP. Every EP should approach PSA as a complex procedure requiring high-level skills and knowledge. Initially, understand that PSA represents a spectrum of goals, from anxiolysis and pain relief to deep sedation. Assess the needs of the patient and the concomitant procedure and set goals accordingly. There is a pharmacopia of drugs that provide sedation and analgesia. Become familiar with their pharmacology, advantages and disadvantages, and indications. This will allow for appropriate usage and achievement of sedation goals. Several drugs that are commonly used for general anesthesia are proving themselves to be safe and efficacious for PSA. Both etomidate and propofol have emerged as useful drugs for PSA. Continued research and practice with these agents will add to our understanding and help define their use for PSA. Performing PSA as a procedure itself requires preparedness, diligent monitoring, and risk awareness. Knowing the patient's comorbid state and choosing agents that will not exacerbate their baseline status minimize risk. Following fasting guidelines is appropriate in certain clinical situations, and is prudent when time permits. However, these guidelines are a benchmark for minimizing risk and are not supported by evidence-based medicine. It is important to be cognizant of the guidelines but also to identify the emergency scenario where action must be taken despite the fasting guidelines. Controlling sedation depth also minimizes the risk of aspiration and other complications. The ETCO2 monitor and Bispectral Index may prove to be useful adjuncts for monitoring sedation depth. However, there is nothing yet that measures sedation depth quantitatively that can replace the qualitative assessment of the EP. More and more PSA is falling under the domain of the EP. It is important for the EP to be involved in hospital policy and guidelines associated with this procedure, and to remain aware of new research in this field. EPs can thereby contribute to quality assurance throughout the medical community by setting a standard in the practice of PSA, as they are not the only practitioners using this procedure. With continued practice and research, expertise in this field will grow measurably.
 ...
PMID:Procedural sedation and analgesia: a review and new concepts. 1582 94

The practitioner of emergency medicine is routinely faced with patients in need of emergent procedures and pain control and sedation. Our challenge is to make our patients' experiences as painless and as safe as possible, while maximizing our ability to perform the procedure at hand; this is not always an easy task given the propensity of each human body to react differently to interventions and stimuli. We can best meet this challenge by understanding how our patients and pharmaceutical agents intermingle in the risk-benefit equation we formulate before starting our "experiment." Coupling this information with fundamentally sound patient care and monitoring will minimize bad experiences with PSA for both the patient and practitioner.
 ...
PMID:Procedural sedation and analgesia in the emergency department: what are the risks? 1582 97

The aim of the study was to assess frequency of various complications of transrectal multifocal biopsy of the prostate (TMBP), to specify prophylactic measures against such complications. Primary TMBP under US guidance was made in 612 patients (mean age 65.8 years, mean level of PSA 12.6 ng/ml). TMBP complications include: hematuria (220 patients, 35.9%), hemospermia (166 patients, 27.1%), pain in the perineum and the rectum (189, 30.9%), acute prostatitis (21 patients, 3.4%), acute orchiepididymitis (7 patients, 1.1%), acute urine retention (9 patients, 1.5%), long-term rectal hemorrhage (13 patients, 2.1%), loss of consciousness during the biopsy (7 patients, 1.1%). The analysis of TMBP complications leads to the conclusion that adequate preparation of the patients and accurate conduction of the prostatic biopsy technique under US guidance make this invasive manipulation diagnostically effective and safe.
 ...
PMID:[Complications of transrectal biopsy of the prostate]. 1598 26

Factors predictive of skeletal-related events (SREs) in bone metastatic prostate cancer patients with hormone-refractory disease were investigated. We evaluated the frequency of SREs in 200 hormone-refractory patients consecutively observed at our Institution and followed until death or the last follow-up. Baseline parameters were evaluated in univariate and multivariate analysis as potential predictive factors of SREs. Skeletal-related events were observed in 86 patients (43.0%), 10 of which (5.0%) occurred before the onset of hormone-refractory disease. In univariate analysis, patient performance status (P=0.002), disease extent (DE) in bone (P=0.0001), bone pain (P=0.0001), serum alkaline phosphatase (P=0.0001) and urinary N-telopeptide of type one collagen (P=0.0001) directly correlated with a greater risk to develop SREs, whereas Gleason score at diagnosis, serum PSA, Hb, serum albumin, serum calcium, types of bone lesions and duration of androgen deprivation therapy did not. Both DE in bone (hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.07-1.25, P=0.000) and pain score (HR: 1.13, 95% CI: 1.06-1.20, P=0.000) were independent variables predicting for the onset of SREs in multivariate analysis. In patients with heavy tumour load in bone and great bone pain, the percentage of SREs was almost twice as high as (26 vs 52%, P<0.02) and occurred significantly earlier (P=0.000) than SREs in patients with limited DE in bone and low pain. Bone pain and DE in bone independently predict the occurrence of SREs in bone metastatic prostate cancer patients with hormone-refractory disease. These findings could help physicians in tailoring the skeletal follow-up most appropriate to individual patients and may prove useful for stratifying patients enrolled in bisphosphonate clinical trials.
 ...
PMID:Predictive factors for skeletal complications in hormone-refractory prostate cancer patients with metastatic bone disease. 1622 9

In this pilot study, the predictive value of Octreotide scintigraphy (Octreoscan) and/or Chromogranin-A (CgA) was investigated in patients with hormone-refractory prostate cancer treated with Octreotide acetate. In total, 20 patients with progressive disease and bone metastases entered the trial. At baseline Octreoscan, CgA, PSA, alkaline phosphates (ALP) and two self-administered questionnaires (EORTC QLQ C-30 (v3) and brief pain index) were performed and a diary of the pharmaceutical was started. The treatment consisted of Octreotide (Sandostatin LAR) acetate 30 mg intramuscular injection every month. The blood samples and questionnaires were repeated every month until 3 months. Clinical responder was defined as a patient with increased global health score more than 10 units and stable or decreased pain score without an increase in analgesic. In all, 17 patients were treated per protocol, and four were assessed as clinical responders. Six patients developed a reduction in ALP (median -26%, range -5 to -78%). All patients increased in PSA. At baseline, three patients had a negative Octreoscan and the patients with positive lesions, demonstrated uptake of low intensity. At baseline the CgA was elevated above the normal range in 15 of the patients, and during treatment five patients decreased their CgA to the normal range. Neither baseline Octreoscan nor CgA could identify the clinical reponders. A minority of patients improves their health-related quality of life. The decrease and normalization of CgA levels in five patients during therapy indicates therapeutic activity but Octreoscan and CgA could not identify clinical responders.
 ...
PMID:Octreotide scintigraphy and Chromogranin A do not predict clinical response in patients with octreotide acetate-treated hormone-refractory prostate cancer. 1623 Oct 13

Surgical or medical androgen deprivation therapy in its multiple variants represents the standard therapeutic approach in the management of metastatic prostate cancer resulting in a primary response rate of about 90%. However, about 90% of the men treated will develop PSA progression within 3-4 years resulting in androgen-independent and later on hormone-refractory prostate cancer. Management of AIPCA and HRPCA still represents a therapeutic challenge despite the development of new and effective treatment options. PSA progression following primary ADT defines an androgen-refractory but still hormone-sensitive PCA which might respond to secondary hormonal manipulations such as antiandrogen withdrawal, addition of nonsteroidal antiandrogens, and administration of estrogens, ketoconazole and hydrocortisone, and somatostatin analogues. Secondary hormonal manipulations will result in a PSA decline >50% in about 60-80% of the patients with a mean duration of 7-17 months depending on the type of treatment. PSA progression following secondary endocrine treatment defines hormone-refractory prostate cancer (HRPCA) which might be treated by systemic chemotherapy. Based on the results of two prospective, randomized clinical phase III trials comparing docetaxel and mitoxantrone, docetaxel results in a statistically significant survival benefit of 2.5 months, a significantly higher PSA and pain response, and represents the treatment of choice in the management of HRPCA. Bisphosphonates such as zoledronate represent another cornerstone in the management of PSA-progressive PCA demonstrating a significant benefit with regard to the prevention of skeletal-related events. Furthermore, bisphosphonates might be indicated in the treatment of symptomatic bone pain as has been demonstrated for ibandronate and zoledronate. The current article critically reflects on the various therapeutic options in the management of PSA progression following primary androgen deprivation for advanced prostate cancer. The development, rationale, and results of systemic chemotherapy are discussed critically and a therapeutic algorithm is demonstrated.
 ...
PMID:[Treatment options for hormone-refractory prostate cancer]. 1623 41

Prognosis in prostate cancer is determined, in greater part, by the presence of metastases. Bone metastases can occur in any part of the skeleton even, for example, at the base of the skull. We present a case of a 78 year old male who, in December 2001, presented with paralysis of the third cranial nerve. The NMR and CAT scans were normal and circulating levels of PSA were elevated. He was referred to the Urology Service where the treatment guidelines included complete androgen block. Subsequently, he developed retro-orbital pain, divergent strabismus and palpebral ptosis. CAT and NMR indicated a soft tissue mass at the sphenoid level. Treatment was Gamma Knife Radio-surgery. Since August 2004, in conjunction with the latest rise in PSA, the patients general status deteriorated considerably and he was referred to the Oncology Service. There was an increase in the paralysis of the third, fourth and sixth cranial nerve (complete left ophthalmoplegia) and left-central facial paralysis. Metastases from prostate cancer can be disseminated via the lymphatic or the blood system. Currently, there are more metastases from large-size tumours. Metastases are critical in prostate cancer because of their adverse effect on the patients survival. Measurements of circulating levels of prostate specific antigen and prostate acid phosphatase are very useful in the clinical diagnosis of the primary tumour, or its metastases.
 ...
PMID:[Ophthalmoplegia in a patient with prostate cancer and bone metastases]. 1623 78


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>