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At least 667 records · Page 37Linked to original sources
PubMed1987

Intrathecal therapy: rationale, technique, clinical results.

In 35 patients a subcutaneously implanted injection port/reservoir was used to provide intrathecal morphine to relieve pain due to cancer. The reservoir offers an alternative to rather expensive devices. It can be used for repeated injections or for infusion. It is easy to locate and facilitates ambulatory treatment. The injections were carried out by members of the patient's family after they had been taught how to do it. Initially, doses of 0.25-0.5 mg of morphine resulted in pain relief for 14 to 24 hours. After 5 weeks of treatment morphine requirements increased to 0.75-2 mg. Side-effects were minimal, and three delayed CSF fistula, two of them confirmed by isotope tracking with Tc99m, closed spontaneously.

Adolescent↗
PubMed1992

The influence of naloxone infusion on the action of intrathecal diamorphine: low-dose naloxone and neuroendocrine responses.

The influence of an intravenous infusion of naloxone 1 microgram kg-1 h-1, in combination with intrathecal diamorphine, on analgesia and hormonal stress responses after laminectomy was assessed in a blinded, randomized, placebo-controlled study. Twenty-seven patients undergoing laminectomy with postoperative analgesia provided by intrathecal diamorphine were investigated. Analgesia was reduced by naloxone (P less than 0.05), and the duration of analgesia was shortened by 180 min. The postoperative concentrations of both blood glucose and serum cortisol were reduced in the naloxone group compared to the control group (P less than 0.05). These results may indicate an excitatory role for the hypothalamic mu receptor in hypothalamo-pituitary-adrenocortical axis regulation.

Adult↗
PubMed1992

Treatment of acute lymphoblastic leukaemia (ALL).

Forty-six consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 23 years (range 14 to 64), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard central nervous system (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate, and monthly intrathecal chemotherapy, with drug intensification comprising either vincristine, adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was achieved in 36 patients (78%) and only the FAB L1 morphology was a significant predictive factor (Chi-squared = 3.91: p < 0.05). Eight of the 10 non-responders had significant drug resistance and 3 deaths were associated with marrow hypoplasia. Median follow-up is 52 months. Median duration of CR is 28 months, median survival of all patients is 16 months, and for those who achieved CR is 44 months. There was no difference between the two maintenance arms. Significant prognostic factors for survival are French-American-British (FAB) subtype, in which the L1 is better than L2 (p = 0.05), and age (p = 0.035). Nineteen patients have experienced medullary relapse and 7 (37%) achieved subsequent CR; this is durable in a single patient who underwent allogeneic bone marrow transplantation. Eight patients (17%) had CNS disease at diagnosis; 5 achieved CR and 1 is alive and disease-free at 65+ months. There has been 1 CNS relapse. These results demonstrate that prolonged remissions and survival can be achieved with this protocol and many patients possibly cured. The level of toxicity is acceptable and the pattern of induction failure indicates that a margin exists for intensifying chemotherapy and thereby possibly further improving results.

Adolescent↗
PubMed1996

Magnetic resonance imaging and neurological evaluation after treatment with high-dose methotrexate for acute lymphocytic leukaemia in young children.

This study evaluates the occurrence of permanent cerebral white matter changes and neurological abnormalities in children treated at a young age for acute lymphocytic leukaemia. Our pilot treatment protocol did not include central nervous system irradiation, but intrathecal methotrexate and high-dose methotrexate infusions followed by very intensive folinic acid rescue. We examined 12 children in complete remission and off therapy 18 months to 9.5 years after their last methotrexate infusion. They were below 5 years of age at diagnosis and therefore expected to be at special risk of neurotoxic sequelae. Cerebral magnetic resonance imaging in the 11 cases thus evaluated did not reveal white matter abnormalities or other signal changes as signs of permanent treatment-related sequelae. We did not observe any pathological clinical neurological findings likely due to methotrexate.

Age Factors↗
PubMed2003

Allosteric adenosine receptor modulation reduces hypersensitivity following peripheral inflammation by a central mechanism.

Activation of adenosine A1 receptors by endogenous adenosine or synthetic agonists produces antinociception in animal models of acute pain and also reduces hypersensitivity in models of inflammatory and nerve-injury pain. Allosteric adenosine modulators facilitate and potentiate the action of adenosine agonists at the A1 receptors. The purpose of the current study was to examine the effect and site of action for an allosteric adenosine modulator, T62 [2-amino-3-(4-chlorobenzoyl)-5,6, 7,8-tetrahydrobenzothiophene], in rat models of acute pain and inflammation. Intrathecal (i.t.) T62 did not change the withdrawal latency or threshold of normal rats to acute heat or to acute paw pressure. In contrast, i.t. T62 reversed thermal hypersensitivity in carrageenin-inflamed rats. Subcutaneous (s.c.) injection of T62 into the inflamed paw had no such effect. To investigate a potential site of action on nociceptors, single-unit afferent activity to mechanical stimuli on A delta- and C-fibers was examined in normal or carrageenin-inflamed rats before and after intravenous (i.v.) T62 administration. Intravenous T62, 3 mg/kg, had no significant effect in either normal or inflamed conditions. These results support previous studies to suggest that adenosine receptor modulators lack efficacy to acute nociceptive stimuli in the normal condition, but reduce hypersensitivity during inflammation through a central mechanism.

Afferent Pathways↗
PubMed2000

The significance of intrathecal opioid therapy for the treatment of neuropathic cancer pain conditions.

The effectiveness of intrathecal opioid therapy when applied to different pain mechanisms, in particular neuropathic and nociceptive pain conditions, was studied retrospectively in 43 patients suffering from cancer pain. On the basis of clinical and radiological data, the pain mechanisms were categorized as nociceptive (n = 23) and neuropathic (n = 20). The average duration of treatment of nociceptive pain was 5 months, of neuropathic pain only 2.5 months. The initial median reduction of pain with intrathecal opioid therapy was 77.8% for nociceptive and 61.1% for neuropathic pain. Long-term results with patients suffering nociceptive pain showed a continuing good median pain reduction of 66.7%. Patients suffering from neuropathic pain showed poor long-term results (11.1% median pain reduction). Neuropathic pain in the extremities reacted least to the application of intrathecal opioids. Optimal results were obtained for nociceptive pain in the trunk area of the body.

Adult↗
PubMed2001

Intrathecal therapy for chronic pain.

With the improved utilisation and widespread availability of opiates, the oral treatment of pain due to malignancy has changed radically, so that the expected need for intrathecal (IT) delivery systems for this pain has largely failed to materialise. Instead, the lack of equal progress in the design and production of non-opiates for treating non-malignant pain, in the long term, has resulted in a greater interest in the development of these IT systems in this non-malignant area.

Administration, Oral↗
PubMed2003

Typical medication errors in oncology: analysis and prevention strategies.

Pharmacotherapy in oncology is complex. It has a small therapeutic range, and is susceptible to errors. Medication errors--especially overdosage--often have serious effects while underdosage entails unnoticed impairment of the therapeutic success. Typical medications and procedures susceptible to errors are described: unintentional intrathecal injections, the application of platinum compounds and anthracyclines, confusion of total and single dose, errors of calculation and preparation, or in operation of infusion pumps. Suitable prevention strategies are standardisation, separation of intrathecal and intravenous chemotherapy, and use of specialized software for planning and calculating chemotherapy, as well as non-punitive notification and recording systems for errors and near-errors in treatment.

Antineoplastic Agents↗
PubMed1984

Prolonged methotrexate infusions in children with acute leukemia in relapse and in remission and with medulloblastoma. Pharmacokinetics, toxicity and clinical results.

In 86 children with acute lymphocytic leukemia (ALL) and in 6 children with medulloblastoma 253 24-hour methotrexate (MTX) infusions with 150, 500, and 700 mg/m2 were performed. MTX concentrations in plasma and cerebrospinal fluid (CSF) were measured with a specific radioimmunoassay. In 131 infusions with 500 mg/m2 given to patients with ALL in remission, the MTX plasma concentration 24 h after the end of infusion did not exceed 7 X 10(-7) mol/1. Mild hematologic toxicity occurred in 22% of the treatment cycles. In contrast 8/45 infusions given to patients with ALL in relapse were associated with delayed MTX elimination followed by severe toxicity. The CSF: plasma ratio of MTX measured during 58 infusions did not exceed 11% in patients with ALL in remission, but was above this value in 13/34 infusions in patients with leukemia of the central nervous system (CNS). 24-hour MTX infusions with 500 mg/m2 were as hepatotoxic as 4- to 6-hour infusions with 3-8.5 g/m2. With MTX as single agent no remissions were achieved in 8 patients with ALL in relapse. The addition of asparaginase in 10 patients resulted in 3 complete and 2 partial remissions. In patients with ALL in first remission clinical results confirmed the value of intensive MTX therapy for disease-free survival.

Actuarial Analysis↗
PubMed2003

Effect on cerebral vasospasm of coil embolization followed by microcatheter intrathecal urokinase infusion into the cisterna magna: a prospective randomized study.

BACKGROUND AND PURPOSE: Vasospasm remains the leading cause of death and permanent neurological disability in patients with aneurysmal subarachnoid hemorrhage (SAH). The objective of our prospective randomized trial of coil embolization followed by intrathecal urokinase infusion into the cisterna magna (ITUKI therapy) was to test its effectiveness in preventing or alleviating the severity of ischemic neurological deficits caused by vasospasm. METHODS: We enrolled 110 patients with ruptured intracranial aneurysms eligible for coil embolization and randomly assigned them to embolization with (n=57) or without (n=53) ITUKI therapy performed within 24 hours of aneurysmal SAH. The incidence of symptomatic vasospasms and the clinical outcomes, based on the Glasgow Outcome Scale, 6 months after SAH onset were assessed. RESULTS: There were no side effects or adverse reactions attributable to ITUKI therapy. Symptomatic vasospasm occurred in 5 patients (8.8%) with and 16 (30.2%) without ITUKI therapy; the difference was significant (P=0.012). Although the mortality rate did not differ between the groups, patients with ITUKI therapy had significantly better outcomes than those without (P=0.036). CONCLUSIONS: Our results demonstrate that ITUKI therapy significantly reduced the occurrence of symptomatic vasospasm. Although it did not completely prevent vasospasms, ITUKI therapy resulted in a lower rate of permanent neurological deficits.

Adult↗
PubMedDate not supplied

Burkitt's lymphoma presenting as oculomotor palsy in an hiv-positive patient.

PURPOSE: To report a case of Burkitt's lymphoma (BL) in an HIV-positive patient presenting as complete third nerve palsy. METHODS: Interventional case report. A 34-year-old man presented with headache, left eye pain, diplopia, and complete ptosis of several hours' duration. Left eye examination disclosed complete third nerve palsy with pupillary involvement. Significant hepatomegalia was noted at physical examination and computed tomography (CT) scan of the abdomen showed multiple solid lesions. RESULTS: Liver biopsy was consistent with Burkitt's lymphoma. Bone marrow biopsy was normal. Brain imaging was normal. Work-up also revealed positivity for human immunodeficiency virus. Chemotherapy treatment was started. Two months later, ocular motility examination was normal. CONCLUSIONS: Although BL affects the central nervous system very rarely, BL should be considered in any immunosuppressed patient presenting with diplopia or ophthalmoparesis.

Adult↗
PubMed1998

High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: is intrathecal chemotherapy necessary?

PURPOSE: Standard treatments for neoplastic meningitis are only modestly effective and are associated with significant morbidity. Isolated reports suggest that concurrent systemic and intrathecal (i.t.) therapy may be more effective than i.t. therapy alone. We present our experience, which includes CSF and serum pharmacokinetic data, on the use of high-dose (HD) intravenous (i.v.) methotrexate (MTX) as the sole treatment for neoplastic meningitis. PATIENTS AND METHODS: Sixteen patients with solid-tumor neoplastic meningitis received one to four courses (mean, 2.3 courses) of HD (8 g/m2 over 4 hours) i.v. MTX and leucovorin rescue. Serum and CSF MTX concentrations were measured daily. Toxicity, response, and survival were retrospectively compared with a reference group of 15 patients treated with standard i.t. MTX during the same time interval. RESULTS: Peak methotrexate concentrations ranged from 3.7 to 55 micromol/L (mean, 17.1 micromol/L) in CSF and 178 to 1,700 micromol/L (mean, 779 micromol/L) in serum. Cytotoxic CSF and serum MTX concentrations were maintained much longer than with i.t. dosing. Toxicity was minimal. Cytologic clearing was seen in 81% of patients compared with 60% of patients treated intrathecally (P = .3). Median survival in the HD i.v. MTX group was 13.8 months versus 2.3 months in the i.t. MTX group (P = .003). CONCLUSION: HD i.v. MTX is easily administered and well tolerated. This regimen achieves prolonged cytotoxic serum MTX concentrations and CSF concentrations at least comparable to those achieved with standard i.t. therapy. Cytologic clearing and survival may be superior in patients treated with HD i.v. MTX. Prospective studies and a reconsideration of the use of i.t. chemotherapy for patients with neoplastic meningitis are warranted.

Adult↗
PubMed1998

Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: an association with intermediate-dose intravenous methotrexate and intrathecal triple therapy--a Pediatric Oncology Group study.

PURPOSE: To describe the incidence of acute neurotoxicity (NT) in children with lower risk B-precursor acute lymphoid leukemia (ALL) treated with intermediate-dose methotrexate (MTX) or divided dose oral MTX with or without intravenous (i.v.) mercaptopurine (MP) and extended intrathecal triple therapy. PATIENTS AND METHODS: Thirteen hundred four patients were entered onto Pediatric Oncology Group (POG) 9005, a randomized phase III trial, between January 11, 1991 and September 1, 1994. After remission induction, patients were randomized to one of three 24-week intensification schedules: regimen A, MTX 1,000 mg/m2 i.v. infused over 24 hours and MP 1,000 mg/m2 i.v. infused over 6 hours; regimen B, low-dose repetitive MTX 30 mg/m2 orally every 6 hours for six doses and i.v. MP; or regimen C, i.v. MTX alone. Intensification was given every 2 weeks for 12 courses. CNS prophylaxis was age-adjusted intrathecal MTX (ITM). In August 1992, the CNS prophylaxis was changed to age-adjusted triple intrathecal therapy (TIT). Reports of grades 3 and 4 acute NT were reviewed. RESULTS: Acute NT was reported in 95 of 1,218 (7.8%) eligible patients treated on POG 9005. The incidence by regimen was regimen A, 46 of 543 patients (8.3%); regimen B, 13 of 354 patients (3.7%); and regimen C, 36 of 321 patients (11.2%) (P < .001). The majority of events were seizures and the median number of days to first occurrence of symptomatic NT after ITM or TIT was 10 to 11 days. Computed tomography (CT) or magnetic resonance imaging (MRI) evidence consistent with leukoencephalopathy (LE), with or without the presence of cerebral calcifications, was observed in 75% and 77.1 % of symptomatic patients treated on regimens A and C, respectively, but in only 15.4% of symptomatic patients treated on regimen B (P < .001). Factors associated with an increased incidence of NT included increased cumulative exposure with repeated i.v. MTX (regimens A and C v B), increased MTX-leucovorin (LCV) ratio (regimens A and C v B), and choice and timing of TIT therapy. The use of i.v. MP during intensification did not appear to contribute to these complications. The switch to TIT CNS prophylaxis was associated with an inferior overall 4-year continuous complete remission (CCR) (P=.031) when compared with ITM. CONCLUSION: Intensification with repeated i.v. MTX in the setting of low-dose LCV rescue was associated with a higher risk for acute NT and LE, especially in patients who received concomitant TIT. The long-term consequences for affected patients remain unknown.

Acute Disease↗