Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Infusions, Spinal”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed2005

Tetanus toxin fragment C fusion facilitates protein delivery to CNS neurons from cerebrospinal fluid in mice.

To improve protein delivery to the CNS following intracerebroventricular administration, we compared the distribution of a human Cu/Zn superoxide dismutase:tetanus toxin fragment C fusion protein (SOD1:TTC) in mouse brain and spinal cord with that of tetanus toxin fragment C (TTC) or human SOD1 (hSOD1) alone, following continuous infusion into the lateral ventricle. Mice infused with TTC or SOD1:TTC showed intense anti-TTC or anti-hSOD1 labeling, respectively, throughout the CNS. In contrast, animals treated with hSOD1 revealed moderate staining in periventricular tissues. In spinal cord sections from animals infused with SOD1:TTC, the fusion protein was found in neuron nuclear antigen-positive (NeuN+) neurons and not glial fibrillary acidic protein-positive (GFAP+) astrocytes. The percentage of NeuN+ ventral horn cells that were co-labeled with hSOD1 antibody was greater in mice treated with SOD1:TTC (cervical cord = 73 +/- 8.5%; lumbar cord = 62 +/- 7.7%) than in mice treated with hSOD1 alone (cervical cord = 15 +/- 3.9%; lumbar cord = 27 +/-4.7%). Enzyme-linked immunosorbent assay for hSOD1 further demonstrated that SOD1:TTC-infused mice had higher levels of immunoreactive hSOD1 in CNS tissue extracts than hSOD1-infused mice. Following 24 h of drug washout, tissue extracts from SOD1:TTC-treated mice still contained substantial amounts of hSOD1, while extracts from hSOD1-treated mice lacked detectable hSOD1. Immunoprecipitation of SOD1:TTC from these extracts using anti-TTC antibody revealed that the recovered fusion protein was structurally intact and enzymatically active. These results indicate that TTC may serve as a useful prototype for development as a non-viral vehicle for improving delivery of therapeutic proteins to the CNS.

Animals↗
PubMed1994

Spinal cord protection: development of a paraplegia-preventive solution.

We present a clinically available method to protect the spinal cord against ischemic or reperfusion injury and to prevent paraplegia after cross-clamping of the aorta. We separated 35 rabbits into five equal groups and clamped each animal's abdominal aorta distal to the left renal artery. We also occluded the aortas 2 cm above the iliac bifurcation for 45 minutes with inflated 5F balloon catheters. Through the catheter port distal to each balloon one of four different solutions was infused at 3 degrees C for 3 minutes at a rate of 5 mL/min (group I, uninfused control; group II, lactated Ringer's solution; group III, lactated Ringer's solution + 30 mg/kg of methylprednisolone; group IV, lactated Ringer's solution+methylprednisolone + 3 mL of 20% mannitol; group V, lactated Ringer's solution+methylprednisolone+mannitol + 10 mg/kg of vitamins E and C). We assessed the neurologic status of the hind limbs on the second postoperative day using Tarlov's criteria. The neurologic status in groups III, IV, and V was significantly superior to that of group I (p < 0.05, groups III versus I; p < 0.01, groups IV and V versus I). Spastic paraplegia occurred in 71% of group I, in 43% of group II, in 29% of group III, in 14% of group IV, and not at all in group V. The infusion of our specially blended solution with several spinal cord neuroprotective properties (hypothermia, methylprednisolone, mannitol, and vitamins E and C) achieved the best spinal cord protection against ischemic or reperfusion injury and prevented postoperative paraplegia.

Animals↗
PubMed1993

Involvement of alpha- and beta-adrenoceptors in antinociception at the lumber spinal level in mice.

To study the role of the adrenergic receptors in the regulation of nociceptive transmission in male albino mice, the antinociceptive activity of adrenergic drugs was tested with a tail-flick method. Subarachnoid infusion of phenylephrine and clonidine into T13-L1 of spinal cord produced a dose-dependent elevation of the nociceptive threshold in sodium pentobarbital anesthetized mice. The inhibitory effect of alpha-adrenoceptor agonists was antagonized by pretreatment with alpha-adrenoceptor antagonists. Isoproterenol also increased the nociceptive threshold significantly. The antinociceptive effect of isoproterenol was reversed by pretreatment with beta antagonist, propranolol. These findings suggest that spinal adrenergic receptors of both alpha and beta types probably are involved in the inhibition of nociceptive transmission.

Analgesia↗
PubMed2003

Implantable baclofen pump as an adjuvant in treatment of pressure sores.

Currently, the success of ulcer treatment is limited by the high recurrence and complication rates. Spasticity is an important contributing factor to ulcer recurrence, and intrathecal baclofen is an effective method to reduce spasticity. Spasticity creates friction, shear, and mobility impairment resulting in wound dehiscence, flap loss, infection, and hematoma. Spasticity can be managed pharmacologically and surgically; baclofen is the drug of choice. Baclofen inhibits spasticity by blocking excitatory neurotransmitters in the spinal dorsal horn. Intrathecal baclofen maximizes the dose delivered to spinal receptors and minimizes the side effects associated with oral baclofen. Case reports of intrathecal baclofen used in patients with pressure sores demonstrate the use of intrathecal baclofen to improve reconstructive outcomes in spastic patients.

Adult↗
PubMed2003

Chemical bladder irritation provokes c-fos expression in the midbrain periaqueductal gray matter of the rat.

We investigated the topographical localization of c-fos expression in the midbrain periaqueductal gray matter (PAG) to detect nociception-induced neural activity in the PAG. In conscious female Wistar rats, c-fos expression was induced by continuous intravesical infusion of saline or 0.1% acetic acid. Number of c-fos protein (Fos)-positive cells was counted at each coronal section of the PAG as well as Barrington's nucleus. Fos-positive cells were also counted at L1 and L6 of the spinal cord, where most of the hypogastric and pelvic nerve afferent terminals project, respectively. Compared with saline infusion, acetic acid infusion provoked irritative bladder responses characterized by a marked increase in the frequency of bladder contractions, and induced a significant increase in the number of Fos-positive cells in both L1 and L6 of the spinal cord. Following acetic acid infusion, there was a significant increase in the number of Fos-positive cells in all coronal sections of the PAG compared with saline infusion, especially in the caudal part of the PAG. The increase in the number of Fos-positive cells was mainly observed in the ventrolateral and lateral parts of the caudal PAG, and in the dorsal part of the rostral PAG. However, there was no difference in the number of Fos-positive cells in Barrington's nucleus between saline and acetic acid infusion. In conclusion, nociception induced by chemical bladder irritation influences neural activity in the PAG. Implication of topographical difference in Fos expression in the PAG and its relevance to changes in bladder function remain to be elucidated.

Acetic Acid↗
PubMed1998

Early protective effects of Iloprost after experimental spinal cord injury.

This investigation was undertaken to study the early protective effects of Iloprost, a stable analogue of prostacyclin, after spinal cord injury in rabbit. Sixteen adult male rabbits (New Zealand Albino) were injured by application of epidural aneurysm clip. Eight rabbits received an intravenous (i.v.) infusion of 30 micrograms kg-1 Iloprost, and eight rabbits received an infusion of saline (SF). Treatment with Iloprost started immediately after spinal cord injury and continued for one hour. Evoked potentials were recorded for each rabbit at one, 15, and 60 minutes after the spinal cord injury. Twenty-four hours later, all the rabbits were deeply anesthetized and spinal cords were removed for histopathological examinations. There was no meaningful statistical difference between cortical somatosensorial evoked potentials (CSEP) of the saline and Iloprost group. However, light and electron microscopic studies showed that the Iloprost treated group had moderate protection of myelin and axons; and limited edema. These results suggest that intravenous Iloprost treatment after spinal cord injury has a highly protective effect without any side effects.

Animals↗
PubMed1997

Axonal regeneration of sensory nerves is delayed by continuous intrathecal infusion of nerve growth factor.

While it is well established that nerve growth factor is growth promoting for sensory neurons in culture, it is unclear whether it serves such a function in vivo. In fact, our previous studies led to the hypothesis that nerve growth factor could actually impair axonal regeneration by reducing the neuronal cell body response to injury. In the present study, the consequence of continuous intrathecal infusion of nerve growth factor on regeneration of sensory neurons was examined in rats given a bilateral sciatic nerve crush. Rats received nerve growth factor (125 ng/h) as a continuous infusion into the subarachnoid space of the lumbar spinal cord via an osmotic minipump (Alzet); controls received cytochrome C. At seven or 10 days, the pump was removed and L4 or L5 dorsal root ganglion exposed and injected with 50 microCi of (3H)leucine. Animals were killed 24 h later, the sciatic nerves removed, cut into 3 mm segments and the radioactivity in each segment determined by liquid scintillation spectrophotometry. Maximal regeneration distances (determined from the front of the resultant transport curves) were similarly reduced (by approximately 6 mm) in nerve growth factor-infused compared to cytochrome C-infused rats. Thus, regeneration rates (determined between eight and 11 days) were unaltered by nerve growth factor infusion; regeneration rates from cytochrome C-infused and nerve growth factor-infused animals were 2.8 mm/day and 3.1 mm/day, respectively. However, nerve growth factor significantly (P < 0.005) increased the delay to onset for regeneration by two days. Taken together, the present study demonstrates that nerve growth factor delays the onset of regeneration without affecting the rate of regeneration. The results implicate the involvement of at least two signals in the regulation of axonal regeneration in dorsal root ganglion neurons. It is suggested that the loss of nerve growth factor serves as an early, induction signal regulating the onset of regeneration and that a second, unidentified signal independently serves to maintain regeneration.

Animals↗
PubMed1994

Treatment of cancer-related pain: when orally administered medications fail.

OBJECTIVE: To summarize the available pain-relieving interventions other than oral medications for cancer-related pain. DESIGN: The pertinent literature is reviewed, and the various options for treating pain in patients with cancer are discussed. MATERIAL AND METHODS: The appropriate situations for use of parenteral administration of opioids, spinal analgesia, neural blockade, and neurosurgical treatment are outlined, and the potential problems and complications associated with these techniques are described. RESULTS: The basic approach to the management of pain in patients with cancer is to begin treatment with less potent analgesic agents early and to progress toward use of more potent pharmaceutical agents, adjuvant drugs, and invasive procedures as needed for alleviation of pain. With parenteral administration of opioids, the dosage can be adjusted rapidly, and therapy can be continued even though a patient may have gastrointestinal dysfunction. A portable ambulatory infusion pump can be used in selected patients. The major advantage of spinal opioid analgesia is the intense analgesia provided with minimal side effects. The potential complications and the availability of treatment alternatives have limited the use of neurolytic blocks, which usually provide only temporary relief of pain. In carefully selected patients with pancreatic or other upper gastrointestinal neoplasms, however, neurolytic celiac plexus and splanchnic nerve blocks are effective. Patients who fail to respond to conservative interventions may be candidates for neurosurgical procedures, such as spinal cord, cortical, or brain-stem stimulation or neuroablative operations (most commonly, cordotomy). CONCLUSION: Cancer-related pain continues to be a major problem, and clinicians should be aware of the availability of effective treatment strategies and techniques. When orally administered medications fail to control pain or cause excessive side effects, patients should be referred to an appropriate specialist or medical center for consideration of other pain-relieving techniques.

Analgesia↗
PubMed1999

Naloxone infusion and drainage of cerebrospinal fluid as adjuncts to postoperative care after repair of thoracoabdominal aneurysms.

The mechanisms that produce paraplegia in patients after TAA repair are complex and involve alterations in regional blood flow to the spinal cord, CSF dynamics, and reperfusion. Although neither the minimal level of blood flow nor the maximal spinal cord pressure that can be tolerated by the spinal cord is known, adjuncts such as CSF drainage and naloxone infusions may allow longer durations of aortic cross-clamping before irreversible ischemia occurs. Because paraplegia is multifactorial and none of the recommended adjuncts alone provides complete protection of the spinal cord, a combination of treatments may be necessary to reduce the prevalence of neurological complications after thoracoabdominal aortic reconstruction. Critical care nurses thus must be acquainted with the advanced monitoring techniques and the pathophysiology behind these new treatment modalities. Advanced assessment skills are also essential to recognize the potential neurological complications that may occur in these patients. Care of patients with TAA is a challenge. Critical care nurses must use multidimensional skills in the areas of hemodynamic monitoring, physical assessment, and psychological counseling to effectively manage postoperative care of these patients.

Adult↗
PubMed2004

Kynurenate in the pontine reticular formation inhibits acoustic and trigeminal nucleus-evoked startle, but not vestibular nucleus-evoked startle.

The startle reflex is elicited by acoustic, trigeminal or vestibular stimulation, or by combinations of these stimuli. Acoustic startle is mediated largely by ibotenate-sensitive neurons in the ventrocaudal pontine reticular formation (PnC). In these studies we tested whether startle elicited by stimulation of different modalities is affected by infusion of the non-selective glutamate antagonist, kynurenate, into the PnC. In awake rats, startle responses evoked by either acoustic or spinal trigeminal nucleus stimulation were inhibited by kynurenate, but not saline, infusions, with the most effective placements nearest PnC. In chloral hydrate-anesthetized rats, kynurenate in the PnC reduced trigeminal nucleus-evoked hindlimb EMG responses, but not vestibular nucleus-evoked startle. Kynurenate in the vestibular nucleus had no effect on trigeminal nucleus-evoked startle. These results indicate that trigeminal nucleus stimulation evokes startle largely through glutamate receptors in the PnC, similarly to acoustic startle, but vestibular nucleus-evoked startle is mediated through other pathways, such as the vestibulospinal tract.

Animals↗
PubMed2006

Best-practice surgical techniques for intrathecal baclofen therapy.

In March 2004, a multidisciplinary conference, "ITB Therapy Best Practice Forum," was held in Minneapolis, Minnesota. The goal of the conference was to develop recommendations for techniques to implant intrathecal baclofen (ITB) pump and catheter systems more effectively and with fewer complications. The authors present the techniques for optimal pump and catheter implantation, including subfascial pump placement; insertion of the Tuohy needle in an oblique, paramedian trajectory; and positioning of the catheter tip at levels commensurate with the therapeutic indication: approximately T10-12 for spastic diplegia, C5-T2 for spastic tetraparesis, and C1-4 for generalized secondary dystonia. Techniques to minimize the incidence of cerebrospinal fluid leakage are described, including the identification of preoperative occult hydrocephalus and the use of a suture ligature around the Tuohy needle at its exit site from the fascia. Techniques to minimize surgery-related infection are also detailed; most involve the use of iodine solutions multiple times intraoperatively. Techniques to insert intrathecal catheters during spinal fusion are addressed, particularly the technique of inserting the catheter cephalad to the fusion site. Panel members advocate the aforementioned techniques to improve the efficacy of and decrease the morbidity associated with ITB therapy.

Baclofen↗
PubMed2006

Intrathecally infused antibodies against Nogo-A penetrate the CNS and downregulate the endogenous neurite growth inhibitor Nogo-A.

Neutralizing antibodies against the neurite growth inhibitory protein Nogo-A are known to induce regeneration, enhance compensatory growth, and enhance functional recovery. In intact adult rats and monkeys or spinal cord injured adult rats, antibodies reached the entire spinal cord and brain through the CSF circulation from intraventricular or intrathecal infusion sites. In the tissue, anti-Nogo antibodies were found inside Nogo-A expressing oligodendrocytes and neurons. Intracellularly, anti-Nogo-A antibodies were colocalized with endogenous Nogo-A in large organels, some of which containing the lysosomal marker cathepsin-D. This suggests antibody-induced internalization of cell surface Nogo-A. Total Nogo-A tissue levels in spinal cord were decreased in intact adult rats following 7 days of antibody infusion. This mechanism was confirmed in vitro; cultured oligodendrocytes and neurons had lower Nogo-A contents in the presence of anti-Nogo-A antibodies. These results demonstrate that antibodies against a CNS cell surface protein reach their antigen through the CSF and can induce its downregulation.

Animals↗
PubMed1998

Pharmacokinetics of ampicillin/sulbactam in patients undergoing spinal microneurosurgical procedures.

The fixed combination of ampicillin (2 g)/sulbactam (1 g) was administered as perioperative prophylaxis at induction of anesthesia in 20 patients undergoing spinal microneurosurgery. It was noteworthy that after the short infusion ampicillin and sulbactam penetrated rapidly from blood into the different tissues affected by the surgical procedures. The following mean concentrations were measured in tissues: muscle 32.3+/-6.5 mg/kg ampicillin and 18.6+/-2.9 mg/kg sulbactam (11.1 min), ligament 39.5+/-11.1 mg/kg ampicillin and 25+/-6.5 mg/kg sulbactam (13.8 min), bone 12+/-3.6 mg/kg ampicillin and 7+/-0.8 mg/kg sulbactam (20.6 min), disk 10.2+/-3.3 mg/kg ampicillin and 7.3+/-1.8 mg/kg sulbactam (44.2 min). The mean time of sampling is given in brackets. For a period of at least 2 h the levels of both drugs measured in serum and in the different tissues were above the MICs for bacteria involved in postoperative wound infections. The administration of ampicillin/sulbactam apparently achieved sufficiently, high antibiotic concentrations, even in bradytrophic tissues such as ligament, bone, and disk, and seemed to meet the pharmacological criteria for perioperative prophylaxis in spinal microneurosurgery.

Adult↗
PubMed2005

Paraplegia secondary to progressive necrotic myelopathy in a patient with an implanted morphine pump.

We present an individual with chronic low back pain who was treated with an implanted morphine pump, which provided very good pain relief for 16 mos. However, the patient developed acute paraplegia secondary to progressive necrotic myelopathy, a rare form of transverse myelitis. The cause of this patient's neurologic deficit was unclear. Three months after the onset of paralysis, a trial of discontinuation of the intrathecal morphine was performed to exclude the morphine as a reversible cause of paralysis. Within 24 hrs after his pump was depleted, his pain became significantly worse. He was maintained on oral opioids for 6 mos, and his pain was only partly controlled, with a daily average visual analog scale score of 7/10. There was no improvement in his neurologic status after stopping the intrathecal morphine therapy, and several consecutive magnetic resonance images of the spine demonstrated radiologic progression of spinal cord involvement. The patient developed classic opioid side effects of excessive somnolence and constipation. Intrathecal morphine therapy was re-instituted, and the patient reported a significant decrease of his pain, an improvement in quality of life, and no complications related to pump functioning.

Analgesics, Opioid↗
PubMed1993

Boron neutron capture therapy: long-term effects on the skin and spinal cord of the rat.

Our studies of the pharmacokinetics of boron focused on the variations in the concentration in blood of Sprague-Dawley rats with time after the administration of single intravenous doses of 50-200 mg/kg of 10B-enriched sodium mercaptoundecahydro-closo-dodecaborate (BSH). After the lowest dose of BSH there was a progressive decline in the boron content of the blood, with a biological half-life (t1/2) of approximately 4.5 h. Higher doses of BSH resulted in slower boron clearance rates. A dose of 100 mg/kg of BSH was the maximum safely tolerated by the rats. The boron content of the skin at this dose of BSH was a factor of 0.6 lower than that in the blood. To determine the dose-related changes in the response of the central nervous system to BNCT-type radiation exposures, a well-established and clinically relevant model, the rat spinal cord, was used. The spinal cords (20 mm field length) of rats, infused with 100 mg/kg of BSH, were irradiated for 3 to 5 h with cold thermal neutrons from the H6 beam on the DIDO reactor (AERE, Harwell). The skin surface neutron flux was 4.8 x 10(8) n/cm2/s. Exposure times of > or = 4 h resulted in vigorous, biphasic skin reactions, indicative of long-term vascular damage in the dermis. Rats were monitored closely for 84 weeks after irradiation. No abnormal neurological responses were observed and there was no histological evidence of lesions in the spinal cord at the end of the study. These findings indicate that the central nervous system has a high tolerance to BNCT-type radiation using BSH as the neutron capture agent.

Animals↗
PubMed2005

Placement of baclofen pumps through the foramen magnum and upper cervical spine.

INTRODUCTION: The baclofen pump has been utilized in children with refractory spasticity. However, in children with prior lumbar fusion, the implantation of such a device is difficult and fraught with complications. As an alternative to placing the pump catheter through the lumbar spine, we report our experience with placement of the catheter in the spinal canal via a cervical approach through the foramen magnum. METHODS: We have followed three patients with prior lumbar fusion and refractory spasticity, each of whom has undergone placement of the intrathecal component of a baclofen pump via the foramen magnum. Appropriate positioning of the catheter tip at the T6 spinal level was determined using intraoperative fluoroscopy. The catheter was then tunneled to the pump in the abdominal wall. RESULTS: All patients experienced a significant decrease in the severity of spasticity with pump placement. The pumps continued to function properly over a follow-up period of 24, 24, and 44 months respectively. In one patient, the catheter recoiled into the subcutaneous tissues several months after its placement, thus necessitating repositioning. One of the pumps was removed 2 years later secondary to a VP shunt infection. However, there were no immediate complications related to placement of the spinal catheter. CONCLUSIONS: Placement of the intraspinal component of a baclofen pump via the foramen magnum is a viable alternative for patients with spastic quadriparesis with prior lumbar fusion. The tip of the spinal catheter can be positioned in the thoracic region in a similar manner to the placement traditional lumbar pumps. In our series, there were no adverse sequelae related to the surgery or catheter positioning.

Adolescent↗
PubMed1990

Influences of neonatal and adult exposures to testosterone on the levels of the beta-subunit of nerve growth factor in the neural tissues of mice.

In our previous report, we have shown the sex difference in the concentration of the beta-subunit of nerve growth factor (beta-NGF) in the neural and paraneural tissues of mice. In this investigation, we examined the effects of castration of adult males, and of neonatal and/or adult treatments with testosterone on levels of beta-NGF in the several tissues of mice. Castration caused a marked reduction in the levels of serum testosterone and of beta-NGF in the brain, spinal cord and submandibular glands, but not in the pancreas and kidneys. Continuous infusion of testosterone for one week into adult males that had been castrated at 2 months of age restored the level of beta-NGF in the three tissues mentioned above. A single injection of testosterone to 5-day-old female pups to masculinize the brain gave no effect on the level of beta-NGF in any tissue dissected after 4 months. A one-week infusion of testosterone into adult females slightly increased levels of beta-NGF in the brain and spinal cord, but the same treatment of adult females given in advance a single dose of testosterone at 5 days of age caused a significant increase in its levels over those of untreated females. These results suggest that neonatal and adult exposures to testosterone can influence the endogenous concentration of beta-NGF in the brain and spinal cord.

Aging↗