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At least 595 records · Page 33Linked to original sources
PubMed1987

A comparative study on the pharmacokinetics of methotrexate in a dose range of 0.5 g to 33.6 g/m2 in children with acute lymphoblastic leukemia.

Concentrations of methotrexate have been determined in the serum and cerebrospinal fluid after 406 infusions of methotrexate to 58 children with acute lymphoblastic leukemia. The dose of methotrexate varied between 500 mg/m2 and 33,600 mg/m2. Pharmacokinetic analysis of the data has been carried out. The effect of dose, age, and number of treatments on steady-state concentration, serum half-life, cerebrospinal fluid (CSF) serum distribution ratio, volume of distribution, systemic clearance of methotrexate was examined. The elevation of dose resulted in a nonproportional increase of the steady-state concentrations both in serum and CSF. The great inpatient and interpatient variations of steady-state concentrations caused only statistically not significant differences in the parameters of different subgroups of dosages. Correlation was found between concentrations of methotrexate in serum and CSF. One to 4 years old children were found to have lower steady-state concentrations of methotrexate in the serum and CSF, greater volume of distribution and faster clearance of the drug. Dose-dependency and age-dependency of methotrexate pharmacokinetics has been concluded.

Acute Disease↗
PubMed1986

Cerebrospinal fluid pharmacokinetics of intrathecal morphine sulfate and D-Ala2-D-Leu5-enkephalin.

Using an implantable pump system to deliver drugs and sample cerebrospinal fluid (CSF), we assessed rostral redistribution and systemic uptake after intrathecal bolus injection and steady-state infusion of morphine sulfate and the opioid peptide D-Ala2-D-Leu5-enkephalin (DADL) in two patients. Following bolus injection, the mean CSF elimination half-lives for morphine sulfate and DADL were 94 and 115 minutes, respectively. With the catheter tip at L2, the ratio of lumbar to cisternal (L/C) concentrations of morphine sulfate was about 7:1, and with the catheter tip at T10, the L/C ratios of morphine sulfate and DADL were approximately 2:1, indicating that this ratio is dependent in part on the level of intrathecal drug administration. CSF levels of morphine sulfate at steady state were three orders of magnitude higher than those in plasma. The CSF pharmacokinetics of morphine sulfate and DADL are similar, with supraspinal redistribution of these opioids via the CSF likely playing an important role in the generation of analgesia and central nervous system side effects.

Enkephalin, Leucine↗
PubMed1995

Influence of baclofen upon the alpha-motoneuron in spasticity by means of F-wave analysis.

Intrathecal baclofen dramatically improves severe spastic syndromes. This improvement is likely related to reduced excitability of alpha-motoneurons. To investigate the influence of baclofen upon the alpha-motoneuron, we analyzed F-waves before and after intrathecal baclofen bolus injection (usually 50 micrograms) as well as after administration of different, constantly delivered doses (60-200 micrograms/day). Intrathecal baclofen bolus decreased the maximum F-wave amplitude (Fp) from an initial value of 9% of the maximum M amplitude (Mmax) (= F/M-ratio) to 2.4% of the Mmax after 130-180 min, reduced the mean F-wave amplitude 60% within 150 min, and shortened the mean duration by 40-60% after 130-180 min. Constantly delivered baclofen of 100 micrograms/day reduced the F/M-ratio from 5% to 2%, the mean F-wave amplitude by 40-80%, and the F-wave mean duration by 40-80%. The minimum F-wave latency did not change after bolus or during steady state administration. The findings indicate that the F-wave mean and maximum amplitude as well as the mean duration are altered in a quantifiable manner following intrathecal baclofen application.

Baclofen↗
PubMed2008

Favorable response of intraommaya topotecan for leptomeningeal metastasis of neuroblastoma after intravenous route failure.

A 3-year-old male, diagnosed with stage 4 neuroblastoma, developed recurrent leptomeningeal metastasis after multi-modality treatment including multi-agent chemotherapy, surgery, high dose chemotherapy plus stem cell rescue, cis-retinoic acid and intravenous (IV) topotecan. He then received intraommaya (IO) topotecan three times weekly (maximum dose; 0.4 mg). A complete response was achieved by a resolution of malignant cells in cerebrospinal fluid and resolution leptomeningeal enhancement by brain MRI. Treatment toxicities included low-grade fever and minimal headache. The duration of treatment response from IO topotecan was 18 weeks. The survival time from CNS recurrence in this patient was 13 months. We suggest IO topotecan be considered for neoplastic meningitis of tumors with known sensitivity to topotecan.

Antineoplastic Agents↗
PubMed2000

Mechanism of the hypotensive action of Rhazya stricta leaf extract in rats.

The hypotensive action of Rhazya stricta lyophilized leaf extract was found to be partly caused by the electrolyte content of the extract, and partly caused by a strongly basic alkaloidal fraction (AF). AF (0.05-1.6 mg animal(-1)) caused a dose-dependent reduction in mean arterial blood pressure (MAP) of urethane-anaesthetized rat preparations. In naiuml;ve pithed rats, AF administration (0.5-2.0 mg animal(-1)) significantly increased MAP. In pithed or spinalized rats made normotensive by noradrenaline infusion, AF (0.25 mg animal(-1)) did not cause any significant changes. Direct intracerebroventricular injection of AF (0.1-0.4 mg) markedly and significantly reduced MAP. It is suggested that the hypotensive action of AF to be mediated by a central mechanism.

Alkaloids↗
PubMed1985

Effective treatment of lymphomas of Burkitt's type and B-ALL in adults.

Malignant lymphomas, Burkitt's type, and B-ALL are rarely encountered in adult patients. Rapid initial responses are usually followed by early relapse and death. In a pilot study four adult patients, two presenting with B-ALL, were successfully treated with an aggressive protocol developed by the BFM study group for childhood lymphomas of B-type. Rapid clearance of tumor masses was achieved in all patients; no relapse occurred during an observation period ranging from 19-33 months of complete remission.

Adolescent↗
PubMed1992

Failure of thiamphenicol in a penicillin-allergic patient with Listeria meningoencephalitis--delayed cure following penicillin desensitization.

A 27-year-old woman, without compromised immunodefenses, experienced a Listeria meningoencephalitis, with brainstem symptoms. The identified agent exhibited poor susceptibility to usual effective antibiotics, except for penicillins. Knowledge of past history of an allergic reaction to beta-lactam antibiotics lead to appropriate therapy after acute intravenous desensitization of the patient to amoxicillin. Treatment resulted in therapeutic administration rate over 24 h, and in rapid regression of clinical and biological disorders.

Adult↗
PubMed1996

Intrathecal immunotherapy in CNS tumors disseminating via CSF: preliminary evaluation using different treatment schedules.

Eight patients affected by central nervous system tumours disseminating via cerebrospinal fluid received rIL-2 immunotherapy according to three different protocols involving intrathecal administration followed or not by systemic infusion. Immunological monitoring included serial evaluation of CSF leukocytes, CSF and peripheral blood CD3-CD56+ cells, and NK activity. The most marked rise in CSF leukocyte levels was induced by daily intrathecal rIL2 administration, which also induced increased PB NK activity. Systemic rIL2 infusion following intrathecal treatment maintained a high percentage of CSF CD3-CD56+ cells, but not CSF leukocytes at high levels. Clinical conditions improved after treatment in two patients, worsened in one and remained substantially unchanged in the remaining five. The side effects of intrathecal rIL2 treatment included fever, confusion, and seizures, and there were marked interindividual variations in the immunological response.

Adolescent↗
PubMed2006

Remote neurotrophic support of epidermal nerve fibres in experimental diabetes.

AIMS/HYPOTHESIS: The support of distal regenerating axons and epidermal nerve fibres through growth factor delivery may depend on the site of delivery. While low-dose systemic insulin provides trophic support for regenerating axons or axons from diabetic animals, its potential action upon the most distal neurites within the epidermis is unknown. In diabetic neuropathy, distal loss of axons is an important clinical and pathological feature. We hypothesised that insulin and IGF-1 delivered intrathecally could support the most distal epidermal nerve fibres. MATERIALS AND METHODS: As insulin and IGF-1 receptors are present upon sensory ganglion perikarya, we studied the impact of intrathecal delivery of low-dose insulin and equimolar IGF-1 on the density of epidermal axons expressing protein gene product 9.5 in experimental diabetic rats. After 2 months of diabetes induced by streptozotocin injection, intrathecal delivery of low-dose insulin or IGF-1 or saline was provided for 1 month, with comparison to compatible doses of subcutaneous insulin delivery. RESULTS: Diabetes, in itself, was associated with a decline in epidermal nerve fibre density. Delivery of both intrathecal IGF-1 and insulin was associated with significant improvement in epidermal fibre density (greatest with IGF-1) and length relative to placebo. CONCLUSIONS/INTERPRETATION: Central intrathecal delivery of IGF-1 and insulin offers remote support for epidermal nerve fibres, subjected to 'dying-back' in early diabetic polyneuropathy.

Animals↗
PubMed1999

Clinimetric issues of screening for responsiveness to intrathecal baclofen in dystonia.

OBJECTIVES: In this study we address clinimetric issues that pertain to the screening of responsiveness to intrathecal baclofen (ITB) in dystonia. METHODS: Eight patients with severe dystonia, who did not respond to oral medication, were evaluated in a double-blind placebo controlled ascending dose screening procedure, which included a randomised sequence of injections of 25, 50 and 75 microg baclofen and placebo. Self-assessments of dystonia severity on a visual analogue scale (VAS) and the Dyskinesia Rating Scale (DRS) were carried out at baseline 1, 4 and 8 hours after a bolus injection. RESULTS: Compared to the VAS, the DRS lacked responsiveness in all patients. Baseline scores of the VAS scores varied considerably between and within patients and underscore the need to express response scores in relation to the baseline. After placebo administration some patients showed a persistent improvement of about 30% across the day, while at some assessments improvements of >50% were noted. Based on the aforementioned findings, a responsiveness coefficient was used which relates the baclofen effect size to the non-specific score changes that may occur as a placebo effect or as random fluctuations in dystonia. Four patients with a responsiveness coefficient >2 received pump implantation and did well on continuous infusion of ITB. Several side effects occurred during the screening procedure, but none interfered with the execution of the screening procedure. CONCLUSIONS: This study demonstrates important clinimetric issues that need to be taken into account when screening for responsiveness to ITB.

Adolescent↗
PubMed2006

Intrathecal analgesic drug therapy.

Intrathecal analgesic infusion therapy through an implantable pump system is a sophisticated medical therapy for those who suffer from chronic, severe pain who are unresponsive to traditional medical therapy. This article describes the patient selection and monitoring process and reviews available intrathecal medications and combinations.

Analgesics↗
PubMed1989

Role of cervical lymph nodes in the systemic humoral immune response to human serum albumin microinfused into rat cerebrospinal fluid.

The humoral immune response to human serum albumin (HSA) microinfused into cerebrospinal fluid (CSF) has been measured in serum, cervical lymph nodes, and spleen of Sprague-Dawley rats. Conditions were designed to promote normal brain barrier function. Serum titers of anti-HSA antibodies, primarily IgG, increased over 10 days and then persisted for at least 10 weeks. A significant role for cervical lymphatics in the systemic response to CSF-administered HSA is suggested, based on results showing that (1) cervical lymph obstruction reduces serum titers of anti-HSA antibodies, and (2) total antibody production by combined superficial and deep cervical nodes, sampled 14 days post-immunization, exceeds that by the spleen.

Animals↗
PubMed1987

Retrospective consideration of the doses of morphine given intrathecally by chronic infusion in 163 patients by 19 physicians.

A retrospective, multi-physician survey was carried out to examine the infusion concentrations of morphine delivered intrathecally by continuous infusion pumps placed to control pain. Replies from 19 physicians formed the basis for a population of 163 patients who received morphine by continuous infusion delivered by an Infusaid pump through a chronically implanted intrathecal catheter (N = 130 for pain of a metastatic origin; N = 3 for non-metastatic pain; N = 30 undefined). These patients received a total of 3443 patient weeks of infusion. The median infusion duration was 13 weeks (+/- 1 quartile: 5-24 weeks). Examination of the concentrations employed revealed that the maximally employed concentration was 1 mg/ml (885 patient weeks). Of the 163 patients, 151 patients received no concentration of morphine sulfate higher than 10 mg/ml. The highest reported concentrations used were around 35 mg/ml. No pathological sequelae related to the infusion of any dose of the opiates were reported. Cumulating the experience with morphine solutions of 8.9 and 10 mg/ml reveals a total of 472 patient weeks in 29 patients. Analysis of the change in infusion dose over time in cancer pain patients revealed a prominent time-dependent increase (N = 130) from 4.8 +/- 0.4 mg/day (N = 130) to 21 +/- 9 mg/day at 52 weeks (N = 10; mean +/- S.E.M.). Though the group morphine utilization rose, examination of the patient population which was infused for periods in excess of 3 months indicated that 48% showed less than a 2-fold increase in dose by 3 months.

Chronic Disease↗
PubMed1991

Subcutaneous lidocaine for treatment of neuropathic cancer pain.

Three patients with terminal malignancy reporting ineffective analgesia using systemic and subsequently spinal opiates were treated with subcutaneous infusion of 10% lidocaine hydrochloride. During the infusion, reasonably stable blood concentrations were achieved and maintained using a subcutaneous infusion at varying dose rates over days to months with improvement of the pain complaints which continued to be refractory to conventional analgesics. Blood lidocaine levels obtained at regular intervals revealed effective concentrations between 2 and 5 micrograms/ml for each patient.

Female↗