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PubMed2000

The hyper-CVAD regimen in adult acute lymphocytic leukemia.

The regimen of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) has demonstrated significant activity in adult lymphocytic leukemia (ALL) and in other hematologic malignancies, including Burkitt's disease, lymphoblastic lymphoma, mantle cell lymphoma, and multiple myeloma. This article presents the rationale for the development of this regimen, describes the program, summarizes the results of the large clinical trials developed at the University of Texas M. D. Anderson Cancer Center, and discusses strategies to improve the results.

Adolescent↗
PubMed2003

Mechanisms of action of intrathecal medications.

Intrathecal delivery of medications for the management of chronic pain syndromes reflects a modern targeted delivery system with the potential for even greater efficacy than is outlined in Tables 1 and 2. The twentieth century ushered in the development of parenteral approaches of medical therapy for chronic pain and other diseases that were superior to the traditional oral delivery methods known in the preceding century. Targeted drug delivery represents a significant advancement in the treatment of patients with chronic pain and is likely be the method of choice for the twenty-first century. This method of delivery is best represented by current drug delivery systems, such as the intrathecal drug pump. Traditional pharmacologic agents will still be used in the twenty-first century; however, the development of novel compounds, transplanted tissues, and genetic engineering will likely usher in a new era of pain management, including their use as analgesics for intraspinal infusion.

Analgesics↗
PubMed1998

Nonionic compact dimers: a new generation of isosmolar iodinated contrast media with low viscosity.

RATIONALE AND OBJECTIVES: The authors evaluated compact dimers, a new class of molecule designed to reduce the osmolality of concentrated solutions of x-ray contrast media without increasing their viscosity. MATERIALS AND METHODS: Molecular modeling was used to design a new hexaiodo dimeric structure with low viscosity and good shielding of hydrophobic areas. This design ends in the synthesis of different prototypes, the structure of which was characterized by a single bond between two perpendicular rings and the presence of tertiary amides. The validity of this approach was investigated with measurements of physicochemical properties (viscosity, osmolality, logP) and pharmacologic studies (urinary and biliary excretion, intravenous and intracerebral medial lethal dose). RESULTS: Solutions of the compact dimers at a concentration of 350 mg of iodine per milliliter combine osmolalities that are close to that of blood with viscosities at ambient temperature nearly half those of commercially available dimers. Furthermore, these new compounds have a tolerance level comparable with that of currently used nonionic media (intravenous median lethal dose, > 17.5 g of iodine per kilogram). CONCLUSION: The three-dimensional structure of the compact dimers has made it possible to control both physicotoxicity and chemotoxicity by combining isotonicity and low viscosity with good tolerance.

Animals↗
PubMed2001

Intrathecal baclofen for generalized dystonia.

The aim of this study was to evaluate the effects of intrathecal bacolfen (ITB) on patients with severe generalized dystonia. Eighty-six participants ranging in age from 3 to 42 years (median age 13 years) with generalized dystonia refractory to oral medications were offered treatment with ITB. Dystonia was associated with cerebral palsy in 71% of participants. Response to ITB was tested by continuous infusions in 72%, and by bolus injections in 17% of participants who had both dystonia and spasticity. Ninety-one percent of participants responded to the screening infusion and 93% to the bolus injections. Pumps were implanted in 77 participants. Dystonia scores at 3, 6, 12, and 24 months were significantly decreased (p<0.005) compared with baseline scores. Dystonia scores were significantly lower in those with intrathecal catheters positioned at T4, or higher than in those with catheters at T6 or lower (p=0.005). Ninety-two percent of participants implanted with a pump retained their responses to ITB during a median follow-up of 29 months. Patient questionnaires indicated that quality of life and ease of care improved in 86% and speech improved in 33%. Side effects of ITB occurred in 26% of participants. Surgical complications occurred in 38% and included CSF leaks, infections, and catheter problems. ITB is probably the treatment of choice for generalized dystonia if oral medications are ineffective.

Adolescent↗
PubMed2001

Successful treatment of invasive mould infection affecting lung and brain in an adult suffering from acute leukaemia.

We describe in detail a 67-yr-old woman who was treated with a cytostatic combination chemotherapy for newly diagnosed common-acute lymphoblastic leukaemia. At the end of induction therapy, the patient acquired invasive mould infection affecting lung and brain. The patient entered complete remission of her leukaemia. Treatment with liposomal amphotericin B was initiated along with surgical excision of the fungal brain abscess. Intrathecal instillation of amphotericin B deoxycholate was started using an Ommaya reservoir because of an anatomical connection between the postoperative cavity and the ventricle. Full dose cytostatic chemotherapy was continued with little delay. A computerised tomography scan of the chest performed 2 months later revealed no fungal abscesses. Magnetic resonance imaging of the brain did not reveal any fungal manifestation. During maintenance therapy/week 69, the patient relapsed from leukaemia. High doses of intravenous liposomal amphotericin B were administered prophylactically. The patient's leukaemia proved refractory to reinduction chemotherapy and the patient died from pneumonia 8 wk later. Post mortem microbiological investigation and histopathological examination of lung and brain tissue did not reveal any macroscopical or microscopical fungal manifestations. This case underlines the feasibility and successful application of combined antileukaemic, antifungal and surgical therapy in a patient with acute leukaemia.

Aged↗
PubMed2003

Successful treatment of meningoencephalitis caused by methicillin-resistant Staphylococcus aureus with intrathecal vancomycin in an allogeneic peripheral blood stem cell transplant recipient.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common infectious pathogen during stem cell trans-plantation. We report a case of meningoencephalitis with multiple abscess formation caused by MRSA, which occurred in a 4-year-old boy soon after allogeneic peripheral blood stem cell transplantation. We successfully cured the infection with a combination of intravenous and intrathecal vancomycin.

Anti-Bacterial Agents↗
PubMed2001

Continuously infused intrathecal baclofen over 12 months for spastic hypertonia in adolescents and adults with cerebral palsy.

OBJECTIVE: To determine if the continuous intrathecal delivery of baclofen will control spastic hypertonia caused by long-standing cerebral palsy (CP). DESIGN: Case series. SETTING: Tertiary care outpatient and inpatient rehabilitation center directly attached to a university hospital. PATIENTS: Thirteen CP patients (average age, 25yr; range, 13--43yr) with intractable spastic hypertonia and quadriparesis (one of whom had predominate diplegia) who had not responded to oral medications including baclofen. INTERVENTION: Patients were screened via a bolus injection of baclofen intrathecally. Those who dropped an average of 2 points on their lower extremity (LE) Ashworth scores were offered computer-controlled pump implantation for 12 months of continuous delivery of intrathecal baclofen (ITB). MAIN OUTCOME MEASURES: Ashworth rigidity scores, spasm scores, and deep tendon reflex scores were collected for both the upper extremities (UEs) and LEs. Differences over time were assessed via descriptive statistics and Wilcoxon's signed-rank test. RESULTS: After 1 year of continuous ITB treatment, the average LE Ashworth score +/- standard deviation decreased from 3.4 +/- 1.2 to 1.5 +/- 0.7 (p <.0001), spasm score from 1.4 +/- 1.6 to 0.6 +/- 1.2 (p =.1024), and reflex score from 2.5 +/- 1.2 to 0.7 +/- 1.1 (p <.0001). The average UE Ashworth score decreased from 3.0 +/- 1.2 to 1.7 +/- 1.0 (p <.0001), spasm score from 1.2 +/- 1.6 to 0.2 +/- 0.6 (p =.0135), and reflex score from 2.3 +/- 0.7 to 0.5 +/- 0.9 (p <.0001). The average ITB dose required to attain these effects at 1 year was 263 +/- 91microg continuously infused per day. CONCLUSION: Continuously infused ITB can reduce spastic hypertonia in the UEs and LEs associated with long-standing CP. This reduction in tone will allow more freedom of movement and the potential for improved function.

Adolescent↗
PubMed2002

Calculation methods for the continuous intrathecal infusion of a solution containing two or three drugs.

The continuous intrathecal infusion of drugs with implantable and programmable pumps is commonly used for the treatment of otherwise intractable pain and spasticity. There is now a consensus that it is possible to use mixtures of two or even three drugs in selected cases. The calculation of the parameters of the pump is easy for a single drug, but it becomes more complicated for a combination of two or three drugs. This paper offers some algebraic formulae that make easier and faster the calculation of the following values: the flow of the pump, the volume of each drug solution to be added to the final mixture, the concentration of each drug in the mixture and the duration of the infusion. These values are determined from the desired quantity of each drug to be infused in 24h, the concentration of each drug solution and the volume of the reservoir. It is essential that the drugs do not react with one another, that they will remain stable in the reservoir at body temperature and that they are safe for a long-term infusion.

Algorithms↗
PubMed2001

Morphine and alternative opioids in cancer pain: the EAPC recommendations.

An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical strategies for dealing with difficult situations are described presenting a consensus view where supporting evidence is lacking. The strength of the evidence on which each recommendation is based is indicated.

Administration, Oral↗
PubMed2004

[Aseptic meningitis after intrathecal infusion of a parenteral nutrition solution: examples of rare malpositions of central venous catheters in preterm neonates].

BACKGROUND: Central venous catheters are an indispensable part of intensive care. In the management of preterm neonates, these are introduced after puncture of a peripheral subcutaneous vein. The catheters are supposed to be pushed forward with the venous flow. A chest X-ray is usually performed for verification of the position of the catheter. Localization of the tip of the catheter is often very difficult because of its extremely small diameter. METHODS: A malposition of a central venous catheter resulting in intrathecal infusion of parenteral nutrition and subsequent aseptic meningitis in a preterm neonate is presented. Further cases of catheter malpositions leading to arthrography, arteriography and incorrect position in various parts of the venous system are discussed. DISCUSSION AND CONCLUSION: The case reports demonstrate that wire-guided central venous catheters are not only advanced by the forward blood flow but can also inadvertently end up in undesired sites and may thus induce serious side effects.

Catheterization, Peripheral↗
PubMed1989

[Initial experiences with implanted drug pumps for continuous intrathecal calcitonin therapy in therapy-resistant pain].

The hormone calcitonin has proved itself for some years in the treatment of chronic pain syndromes. In addition to its known influence on calcium exchange it gives vise to an analgesic effect within the central nervous system and this follows systemic administration or after bolus intrathecal injection. Two patients with chronic non malignant pain are presented in whom continuous delivery pumps have been used for intrathecal Lachs-Calcitonin (Karil, Fa. Sandoz).

Brachial Plexus Neuritis↗
PubMed1975

Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections.

The kinetics and distribution of methotrexate in intraventricular and intrathecal cerebrospinal-fluid spaces were studied in patients with meningeal leukemia and meningeal carcinomatosis after drug administration by intravenous infusion, indwelling intraventricular subcutaneous reservoir (Ommaya), or standard lumbar puncture. Negligible ventricular concentrations followed a single intravenous dose. During an intravenous infusion (500 mg per square meter for 24 hours) the ventricular cerebrospinal-fluid concentration rose to 6 times 10-minus 7 M. Methotrexate administered by Ommaya reservoir, at a dose of 6.25 mg per square meter, rapidly distributed in the subarachnoid space; the peak ventricular concentration of 2 times 10-minus 4 M declined exponentially over 48 hours. Lumbar cerebrospinal-fluid concentration reached a maximum of 5 times 10-minus 5 M four hours after injection and then fell exponentially. Administration by lumbar puncture occasionally produced epidural and subdural leakage; even with successful lumbar puncture, ventricular methotrexate concentration varied considerably from patient to patient despite similar doses. Administration by Ommaya reservoir more reliably produced adequate cerebrospinal fluid distribution than administration by lumbar puncture.

Adolescent↗
PubMed1998

Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. AIDS Clinical Trials Group 243 Team.

BACKGROUND: Progressive multifocal leukoencephalopathy affects about 4 percent of patients with the acquired immunodeficiency syndrome (AIDS), and survival after the diagnosis of leukoencephalopathy averages only about three months. There have been anecdotal reports of improvement but no controlled trials of therapy with antiretroviral treatment plus intravenous or intrathecal cytarabine. METHODS: In this multicenter trial, 57 patients with human immunodeficiency virus (HIV) infection and biopsy-confirmed progressive multifocal leukoencephalopathy were randomly assigned to receive one of three treatments: antiretroviral therapy alone, antiretroviral therapy plus intravenous cytarabine, or antiretroviral therapy plus intrathecal cytarabine. After a lead-in period of 1 to 2 weeks, active treatment was given for 24 weeks. For most patients, antiretroviral therapy consisted of zidovudine plus either didanosine or stavudine. RESULTS: At the time of the last analysis, 14 patients in each treatment group had died, and there were no significant differences in survival among the three groups (P=0.85 by the log-rank test). The median survival times (11, 8, and 15 weeks, respectively) were similar to those in previous studies. Only seven patients completed the 24 weeks of treatment. Anemia and thrombocytopenia were more frequent in patients who received antiretroviral therapy in combination with intravenous cytarabine than in the other groups. CONCLUSIONS: Cytarabine administered either intravenously or intrathecally does not improve the prognosis of HIV-infected patients with progressive multifocal leukoencephalopathy who are treated with the antiretroviral agents we used, nor does high-dose antiretroviral therapy alone appear to improve survival over that reported in untreated patients.

AIDS-Related Opportunistic Infections↗
PubMed2000

Effects of intrathecal morphine on the ventilatory response to hypoxia.

BACKGROUND: Intrathecal administration of morphine produces intense analgesia, but it depresses respiration, an effect that can be life-threatening. Whether intrathecal morphine affects the ventilatory response to hypoxia, however, is not known. METHODS: We randomly assigned 30 men to receive one of three study treatments in a double-blind fashion: intravenous morphine (0.14 mg per kilogram of body weight) with intrathecal placebo; intrathecal morphine (0.3 mg) with intravenous placebo; or intravenous and intrathecal placebo. The selected doses of intravenous and intrathecal morphine produce similar degrees of analgesia. The ventilatory response to hypercapnia, the subsequent response to acute hypoxia during hypercapnic breathing (targeted end-tidal partial pressures of expired oxygen and carbon dioxide, 45 mm Hg), and the plasma levels of morphine and morphine metabolites were measured at base line (before drug administration) and 1, 2, 4, 6, 8, 10, and 12 hours after drug administration. RESULTS: At base line, the mean (+/-SD) values for the ventilatory response to hypoxia (calculated as the difference between the minute ventilation during the second full minute of hypoxia and the fifth minute of hypercapnic ventilation) were similar in the three groups: 38.3+/-23.2 liters per minute in the placebo group, 33.5+/-16.4 liters per minute in the intravenous-morphine group, and 30.2+/-11.6 liters per minute in the intrathecal-morphine group (P=0.61). The overall ventilatory response to hypoxia (the area under the curve) was significantly lower after either intravenous morphine (20.2+/-10.8 liters per minute) or intrathecal morphine (14.5+/-6.4 liters per minute) than after placebo (36.8+/-19.2 liters per minute) (P=O.003). Twelve hours after treatment, the ventilatory response to hypoxia in the intrathecal-morphine group (19.9+/-8.9 liters per minute), but not in the intravenous-morphine group (30+/-15.8 liters per minute), remained significantly depressed as compared with the response in the placebo group (40.9+/-19.0 liters per minute) (P= 0.02 for intrathecal morphine vs. placebo). Plasma concentrations of morphine and morphine metabolites either were not detectable after intrathecal morphine or were much lower after intrathecal morphine than after intravenous morphine. CONCLUSIONS: Depression of the ventilatory response to hypoxia after the administration of intrathecal morphine is similar in magnitude to, but longer-lasting than, that after the administration of an equianalgesic dose of intravenous morphine.

Adolescent↗
PubMedDate not supplied

Experimental evaluation of the beneficial effect of an antioxidant on cerebral vasospasm.

Based on the previously suggested hypothesis that generation of free radicals leading to lipid peroxidation is involved in the genesis of vasospasm following SAH, the therapeutic effect of an antioxidant on experimental vasospasm was examined. As an antioxidant suitable for this purpose, AVS(1,2-bis(nicotinamide)-propane) was used. Experimental SAH was induced in dogs by intracisternal injection of blood and subsequent changes in the basilar artery diameter was evaluated by angiography. First, intrathecal administration of AVS 3 days after SAH caused prompt resolution of pre-existing chronic vasospasm for 3-4 h. Next, the effect of continuous intravenous administration of saline (control) or AVS was started and continued for 4 days. In the control group, early and chronic spasm was observed on the daily angiography. In the AVS-treated group, early spasm was only moderately inhibited, but the occurrence of chronic spasm was remarkably suppressed in a dose-dependent manner. In these experiments, no adverse effect of AVS on the neurological or systemic conditions was observed. The data indicate that AVS may be beneficial in the treatment of vasospasm following SAH, thereby reinforcing the concept that generation of free radicals is involved in the genesis of vasospasm.

Animals↗