Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bradykinin analog, Cereport (RMP-7), was designed to increase permeability of the blood brain barrier (BBB). Over the past several years it has been developed primarily as a means of increasing permeability of the blood brain tumor barrier, where early evidence indicated a particularly robust and reliable effect. The present series of experiments were intended to determine whether Cereport might also be used to increase delivery of pharmacological agents across the normal (i.e., non-tumor) BBB. This was accomplished by testing the ability of Cereport to enhance delivery of the peripherally acting opiate agonist, loperamide, to the brain, as evidenced by induction of a centrally mediated analgesic effect. Intravenous administration of a combination of Cereport and loperamide produced a significant analgesic effect (2-fold increase in response times) when animals were tested on a hotplate apparatus. Loperamide alone did not produce analgesia. An analysis of the time course of analgesia revealed a graded onset of analgesia which peaked at 30 min, maintained asymptote at 60 min, and began to diminish by 120 min following Cereport and loperamide administration. Finally, the analgesic effects of combining Cereport and loperamide were completely blocked when animals were pre-treated with the opiate antagonist naloxone, demonstrating that the analgesia was mediated through opiate receptors. Collectively, these results suggest that Cereport was able to increase delivery of loperamide across the BBB, allowing it to gain access to opiate receptors in the CNS to produce a centrally mediated analgesic effect. They therefore provide clear evidence that safe and well-tolerated doses of Cereport can increase permeability of the normal (i.e., non-tumor) BBB. Moreover, they provide the first evidence of a pharmacological effect specifically enabled by controlled (i.e., receptor-mediated) modulation of the BBB.
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PMID:Central analgesic actions of loperamide following transient permeation of the blood brain barrier with Cereport (RMP-7). 972 19

Persistent chest wall pain is common after thoracotomy and is usually caused by recurrence or progression of malignancy. It should prompt efforts to identify and treat the causative disease. A minority of patients experience persistent pain not related to neoplasm. This pain may last for years, but is usually not severe. A small subset of these patients experience persistent severe pain, which may be debilitating. The pain may be owing to various causes. Diagnosis and treatment should be individualized and directed toward the causes believed to be present. First-line pharmacologic therapies include NSAIDs, tricyclic antidepressants, antiepileptics, and low-dose opioids. Some patients require more sophisticated treatment from multidisciplinary pain-management clinics. This treatment may include nerve blocks, physical therapy, sympathectomy, cryoneurolysis, or long-term neuromodulation with epidural analgesia or spinal cord stimulation. Because of the severe pain these patients may experience and the difficulty and expense associated with treatment, prevention may be the best strategy for dealing with this problem. Recent laboratory and clinical studies indicate that minimizing perioperative pain can suppress certain alterations in the nervous system that may prevent the genesis and maintenance of chronically painful conditions. This suggests that strategies for avoiding PTPS may begin with aggressive perioperative anesthetic and analgesic techniques. More effective application of knowledge already available from laboratory studies awaits further clinical trials. New drugs such as NMDA inhibitors hold promise for more effective treatment in the future.
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PMID:Pathogenesis and management of persistent postthoracotomy pain. 974 44

Diagnostic and therapeutic potentials and our first two-year experience with video-assisted thoracic surgery (VATS) are reported. From May 1995 to April 1997, at the Department of Surgery, University Hospital Split, VATS approach was planned in 55 cases (recurrent pneumothorax in 23, tension pneumothorax in 1, traumatic effusion in 5, malignant metastatic lung tumor in 1, benignant lung tumor in 11, traumatic effusion in 5, suspected mediastinal lymph nodes in 4, long lasting unconfirmed pleural effusion in 9, foreign body in 1, mediastanal cyst in 1). Of these, 48 procedures (87.2%) were performed using VATS (diagnostic thoracoscopy in 12, wedge resection with or without pleural abrasion in 21, partial pleurectomy in 1, decortications in 3, mediastinal lymph nodes biopsy in 4, lung biopsy in 7). Seven patients (12.7%) underwent conventional posterolateral thoracotomy. Complications included persistent air leak in three patients, prolonged bleeding in one patient and supraventricular tachycardia in one patient. The mean duration of chest tube drainage after the procedure was 3.7 days (range 2 to 19 days), and mean hospital stay was 5.1 days (range 3 to 15 days). All patients received routine antimicrobial chemoprophylaxis with single-dose ceftriaxone 2 g intravenously immediately prior to the surgery, and average postoperative patient-controlled analgesia with buprenorphine 0.15 mg. We conclude that VATS is a very useful alternative to conventional thoracotomy in managing cases of exploration, recurrent spontaneous pneumothorax, benign pulmonary lesions, solitary pulmonary nodes, early decortications and different intrathoracic biopsies.
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PMID:[Our initial experience with video-assisted thoracoscopic surgery (VATS)]. 981 14

The use of radiotherapy to treat metastatic bone pain is being challenged by claims of high cost and by more readily available, noninvasive treatment approaches. The authors assessed the effectiveness of brief courses of radiotherapy in reducing pain and estimated cost data for a pilot comparison between radiotherapy and narcotic analgesics in patients with cancer. A representative group of outpatients undergoing brief courses of radiotherapy with Karnofsky scores above 70 and without serious comorbidities were recruited from 1995 through 1996. Patients indicated their pain at rest and with movement on a scale of from 1 to 10 both before and up to 12 months after radiotherapy. Radiotherapy costs were estimated from Medicare-allowable charges. Narcotic analgesia costs were estimated from published values. In 66 patients with 131 individually treated sites, median at rest pain score decreased by about 4 points after treatment (5.58 [-/+3.28] before treatment vs. 1.55 [-/+1.8] after treatment; p < 0.05). Median with movement pain score was about 5 points lower after treatment (7.32 [-/+2.72] before treatment vs. 1.94 [-/+2.07] after treatment; p < 0.05). No differences were found when stratifying by type of pain, tumor histologic type, or skeletal site. The estimated cost per patient ranged from $1,200 to $2,500 for radiotherapy. This compares with an estimated cost of $9,000 to $36,000 for 9 months of narcotics. In this pilot study, a brief course of radiotherapy significantly reduced pain and appeared to be cost effective when compared with narcotic analgesia. A full economic evaluation is warranted.
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PMID:Brief courses of palliative radiotherapy for metastatic bone pain: a pilot cost-minimization comparison with narcotic analgesics. 985 68

Distal symmetrical peripheral neuropathy is a common adverse experience in persons with HIV infection. This condition, which presents as a pain, numbness. burning and/or dysaethesia initially in the feet, is often multi-factorial in its origin. Nucleoside analogue reverse transcriptase inhibitors represent an important contributor to peripheral neuropathy. Specifically, around 10% of patients receiving stavudine or zalcitabine and 1 to 2% of didanosine recipients may have to discontinue therapy with these agents due to neuropathy. Prompt withdrawal of these therapies enables gradual resolution of signs and symptoms in most patients, although a period of symptom intensification may occur shortly after withdrawal. Risk factors for developing peripheral neuropathy during nucleoside analogue therapy include low CD4+ cell count (<100 cells/mm3), a prior history of an AIDS defining illness or neoplasm, a history of peripheral neuropathy, use of other neurotoxic agents including high alcohol (ethanol) consumption and nutritional deficiencies such as low serum hydroxocobalamin levels. Thus, patients at increased risk of peripheral neuropathy should potentially avoid the use of the neurotoxic nucleoside analogues or be more carefully monitored during therapy. Management of this problem includes patient education. prompt withdrawal of the likely causative agent (giving consideration not to leave the patient on a sub-optimal therapy regimen) and simple analgesia. with augmentation with tricyclic antidepressants or anticonvulsant agents when pain is severe. New agents that may assist in managing this condition include levacecarnine (acetyl-L-carnitine) and nerve growth factors such as recombinant human nerve growth factor.
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PMID:Peripheral neuropathy with nucleoside antiretrovirals: risk factors, incidence and management. 988 91

Perioperative morbidity in elderly patients has decreased in last years, with the advent of newer surgical, anaesthetic and monitoring techniques, but is still important when compared with that of younger patients. Complications in the post-operative show different frequencies and mainly depend: a) on age-related conditions of pulmonary, cardiovascular and renal functions, of C.N.S. and of nutritional status; b) on surgery and medication-related risk factors, inclusive of emergency, bedrest, analgesia and infusions, drugs and intensive care; c) on neoplastic or non-neoplastic disease, type of surgery and surgeon's experience. Appropriate surgical intervention, therefore, should not be deferred because the patient is elderly, but surgeon must look beyond measured indices to the qualities of vitality and motivation.
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PMID:Age related risk and prevention of postoperative complications. 1010 Apr 6

Opioids used topically may exercise several useful clinical effects. Opioids may cause immediate local analgesia and also may work indirectly through decreasing the inflammation process. In this article we describe six patients treated with topical opioids because of cutaneous pain due to tumor infiltration. skin ulcers of malignant and non-malignant origin, severe oral mucositis, pain due to knee arthrosis and severe tenesmoid pain. In all but one case, topical morphine provided rapid relief which lasted usually for 7-8 h. The side effects of topical opioids were none or minimal. Possible mechanisms of topical analgesia are discussed.
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PMID:Potential uses of topical opioids in palliative care--report of 6 cases. 1020 24

Chronic pain associated with neoplastic disease can be difficult to treat. The development of a computerized ambulatory, patient-controlled analgesia (PCA) pump may provide the patient and clinician with an alternate approach in management of chronic cancer pain. The pump delivers a constant infusion of analgesic and allows for additional on-command doses for breakthrough pain. Patients with chronic cancer pain poorly controlled with conventional narcotic regimens were eligible for this trial. Four patients were included in this trial. Upon admission, each patient was started on a morphine infusion via a peripheral site and titrated to an effective dose. Once the optimal dose was achieved, the patients were converted to the ambulatory pump. The pump was programmed to deliver identical morphine infusions and any PCA doses. Infusion access was provided by a long-term central venous catheter or subcutaneous infusion set. Final maintenance infusions ranged from 0.8 to 60 mg morphine per hour. Three patients required PCA doses. Patients and family members were trained on catheter care and operation of the infusion pump. At home, patients reported acceptable pain relief while engaging in many activities of daily living. Complications included constipation, possible drug tolerance, and accidental catheter removal. Overall, patient acceptance of the pump was good with improved pain control, minimal adverse reactions, and ease of use at home.
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PMID:Management of chronic cancer pain using a computerized ambulatory patient-controlled analgesia pump. 1029 60

INTRODUCTION: Mucositis induced by antineoplastic drugs is an important, dose-limiting, and costly side effect of cancer therapy. The ulcerative lesions produced by mucotoxic chemoradiotherapy are painful, restrict oral intake and, importantly, act as sites of secondary infection and portals of entry for the endogenous oral flora. The overall frequency of mucositis varies and is influenced by the patient's diagnosis, age, level of oral health, and type, dose, and frequency of drug administration. Some degree of mucositis occurs in approximately 40% of patients who receive cancer chemotherapy. Approximately one-half of those individuals develop lesions of such severity as to require modification of their cancer treatment and/or parenteral analgesia. The condition's incidence is consistently higher among patients undergoing conditioning therapy for bone marrow/peripheral blood progenitor cell transplantation, continuous infusion therapy for breast and colon cancer, and therapy for tumors of the head and neck associating concomitant chemotherapy and radiotherapy. Among patients in the high-risk protocols, severe mucositis occurs with a frequency in excess of 60%. Concomitant with mucositis is often a chemotherapy-induced myelosuppression. The neutropenia that results puts the patient with oral mucositis at significant risk for systemic infection. Patients with mucositis and neutropenia have a relative risk of septicemia that is greater than four times that of individuals without mucositis. The morbidity of all mucositis can be profound. It is estimated that approximately 15% of patients treated with radical radiotherapy to the oral cavity and oral pharynx will require hospitalization for treatment-related complication. In addition, severe oral mucositis may interfere with the ability to deliver the intended course of therapy, leading to significant interruptions in treatment, and possibly impacting on local tumor control and patient survival. It is also not unusual for mucositis to necessitate delays in cancer chemotherapy particularly with those agents that are known to be mucotoxic, including 5-fluorouracil with or without folinic acid, methotrexate, doxorubicin, etoposide, melphalan, cytosine arabinoside and cyclophosphamide. In addition to its impact on a patient's treatment course, on quality of life, and morbidity and mortality, mucositis can also have a significant economic cost. This is particularly true in the autologous and allogeneic bone marrow transplant settings for hematologic malignancies, where the length of hospital stay may be prolonged due to severe mucositis.
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PMID:Mucositis: Its Occurrence, Consequences, and Treatment in the Oncology Setting. 1038 37

No single agent or combination chemotherapy protocol, with the exception of gemcitabine, has so far proven superior to standard bolus 5-fluorouracil regimes for the treatment of advanced pancreatic cancer. The present phase II trial was designed to study whether the effectivity of 5-fluorouracil can be improved with a weekly high-dose 5-fluorouracil schedule. 26 patients with cytologically or histologically verified, metastasized (n = 21) or locally advanced (n = 5) previously untreated adenocarcinoma of the pancreas were included in this study. Treatment consisted of weekly applications of 2,600 mg/m2 5-fluorouracil as 24-h infusion on days 1, 8, 15, 22, 29, 36. Treatment was repeated at day 50 and was continued until disease progression. Primary endpoints of the study were response rates and toxicity, secondary endpoints were survival and clinical benefit in terms of performance status, body weight and analgesia consumption. Toxicity of the regimen was mild with only four instances of grade-3 toxicity. Response rates were 8% (95% CI = 1.2-13.7) with two partial remissions. Improvement of at least one parameter of clinical benefit for > or = four weeks was observed for 11.5% of the study patients. The most prominent effect was a transient stabilization of objective tumor measurements (48% [95% CI = 27.8-68.7]) and individual parameters of clinical benefit (50-75%). Median survival was 248 days (95% CI = 164-459) for all patients included in the study. The present study indicates that the high-dose 5-fluorouracil regimen shows weak activity in advanced pancreatic cancer which seems comparable to gemcitabine.
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PMID:A phase II study of weekly 24-h infusion of high-dose 5-fluorouracil in advanced pancreatic cancer. 1054 93


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