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PubMed1978

Effect of autonomic neural blockade on verapamil-induced suppression of the accelerated ventricular escape beat in ouabain-treated dogs.

The effect of autonomic neural blockade on verapamil-induced suppression of the accelerated ventricular escape beat (AVE) was evaluated in anesthetized dogs pretreated with ouabain. Ouabain (53 +/- 2 microgram/kg, n = 45) was administered in divided doses until simultaneous electrical stimulation of the right atrium and ventricle triggered an AVE. The escape interval of the AVE was stable over a 150-min time period in a group of control animals. Verapamil was infused (20 microgram/kg/min) until the escape interval increased at least 50% or until the AVE was abolished. The total amount of verapamil in milligrams per kilogram that produced this effect was defined as the verapamil endpoint. The verapamil endpoint in vagotomized animals was not significantly different from a group of intact controls. In contrast, the verapamil endpoint in animals pretreated with propranolol, hexamethonium, guanethidine, bretylium or spinal section was significantly less than the control group. Propranolol, hexamethonium, guanethidine or spinal section alone increased the escape interval by a maximum of 12%. Infusion of norepinephrine in spinal animals treated with verapamil restored the AVE. These data indicate that sympathetic nerve activity contributes to the genesis of the AVE and antagonizes the antiarrhythmic effect of verapamil on the escape beat.

Animals↗
PubMed2026

Continuous Intrathecal Infusion of Nivolumab in Advanced Melanoma With Concomitant Leptomeningeal Disease: Efficacy, Safety, and Pharmacokinetics.

BACKGROUND AND OBJECTIVES: Prognosis of melanoma with leptomeningeal disease (LMD) is poor (median overall survival of 5.1 months). Intrathecal (IT) nivolumab appears safe, although its efficacy remains uncertain. We investigated the feasibility, safety, and efficacy of continuous IT nivolumab. METHODS: This was a retrospective analysis of 11 melanoma patients with progressive LMD (MelBase; NCT02828202) treated as part of the patients' care with continuous IT nivolumab administered through spinal (n = 10) or ventricular catheter (n = 1). RESULTS: Patients (5 women, median age 52) with Eastern Cooperative Oncology Group &#x2264;1 (except for 1) and stable extracranial disease (except for 4) were treated over a median duration of 1.5 months and followed for 2.5 months. Seven presented symptomatic LMD. Primary tumors were mostly cutaneous (n = 8) and BRAF-mutated (n = 10). All patients had progressed on systemic immunotherapy; 7 had received brain radiotherapy (whole brain radiotherapy [n = 3]; stereotactic radiosurgery [n = 4]). Concomitant therapies included corticosteroids >10 mg (n = 5), intravenous nivolumab (first 3 months of IT therapy, n = 1), and targeted therapies (n = 7). The median overall survival was 2.5 months, with 3 patients surviving for more than a year. Reversible treatment-related adverse events occurred in 5 patients: meningoencephalitis (grade 3, n = 1), intracranial hemorrhage (grade 1, n = 1), intracranial hypotension (grade 2, n = 2; grade 1, n = 1). Baseline levels of nivolumab in the cerebrospinal fluid (CSF) were <2 &#xb5;g/mL, even among patients with plasma detection. CSF concentrations of nivolumab at steady state varied from 36 to 97 &#xb5;g/mL, with clearances of 4.3-15.7 mL/h. Next-generation sequencing identified CSF genomic profiles correlating with clinical progression in 4 patients. CONCLUSION: These findings warrant further trials on IT nivolumab.

Humans↗
PubMed1979

Anterior spinal artery syndrome--a complication of cervical intrathecal phenol injection.

Spinal nerve block by intrathecal phenol-glycerine infusion is commonly employed for relief of severe pain in terminal carcinomatosis and, frequently, a dramatic regional anesthetic effect is achieved. However, nerve block by this procedure may in very rare instances give rise to serious complications. We have seen a case of terminal malignant melanoma in which clinical manifestations, indicative of anterior spinal artery syndrome, developed following the injection of 0.3 ml of 10% phenol-glycerine into the cervical subarachnoid space at the C4--C5 level for the control of severe right arm pain. This report describes the clinical course of the patient over a period of 4 months after the nerve block and the post-mortem findings along with a brief review of the literature.

Adult↗
PubMed1979

Continuous mini-infusion of bupivacaine into the epidural space during labor. Part I: Radiographic visualization of the epidural catheters.

Two groups, each consisting of 20 parturients, were given a continuous infusion of 0.25 per cent bupivacaine into the epidural space for pain relief, after test and loading doses. The analgesic effect was registered during labor. After delivery the course of the catheters in the epidural space was investigated radiologically. In the first group long catheters (mean 16.5 cm from the skin surface) and in the second group short catheters (mean 10.5 cm) were used. The medial approach in the epidural space was varied between the first and second lumbar interspaces. The relationship between the position of the catheter tip and the degree of analgesia was also studied. In two mothers with fetus mortuus ante partum, the spread of a radiopaque dye solution was followed during labor. Through the force of gravity and the mothers position, the spread of solution covered three segments within 30 minutes. It was concluded, that slow infusion of local anesthetic solution gives satisfactory pain relief if the catheter is inserted into the first lumbar interspace to a depth of 10--12 cm from the skin surface ending close to the Th12 level. Gradual raising of the mother from the supine to the semirecumbent position and regular change of sides during mini-infusion is important for an even spread of the analgesic solution and analgasia.

Anesthesia, Epidural↗
PubMed1979

Use of metrizamide computerized tomographic cisternography in the evaluation of patients with malignant glioma for immunotherapy.

The communication between the subarachnoid space and the surgically created tumor cavity in glioma patients was evaluated by metrizamide cisternography. It was necessary to know the presence or absence of such a communication to determine the route of administration of autologous lymphocytes as a form of immunotherapy. The contrast injections were made either into the spinal subarachnoid space or directly into the tumor cavity. The presence of communication was demonstrated and followed by computerized tomographic (CT) scanning. The results were also corroborated by comparing the white cell counts in the fluid from the tumor cavity and the spinal subarachnoid space 24 hours after autologous lymphoid cell infusion. In only two of seven patients was a communication present. In the five patients without a communication, the blocks were at the tentorial hiatus (one patient), due to a nonpatent subarachnoid space over the cerebral convexity (two patients), and the result of adhesions at the pial margin of the tumor cavity (three patients). In addition, certain limitations in the use of computerized tomography in the evaluation of glioma patients are demonstrated. These problems include the effects of steroids on tumor size, the poor correlation between "enhancement" on CT scan and tumor recurrence, and the difficulty of differentiating metrizamide and hemorrhage by CT scan in the immediate postoperative period. (Neurosurgery, 5: 576--582, 1979).

Adult↗
PubMed1979

Bronchial angiography and intraarterial chemotherapy with mitomycin-C in bronchogenic carcinoma. Anatomy, technique, complications.

Bronchial angiography and intraarterial infusion of mitomycin-C were successfully performed in 39 of 47 patients with bronchogenic carcinoma. More than one course was given to several patients. No neurologic complications occurred and the side effects were insignificant. The pertinent anatomy of the bronchial and spinal arteries is summarized and a comprehensive description of the angiography and infusion technique is given. It is important that the infused artery is not occluded by the catheter and that the drug is properly diluted to avoid complications. The method appears to be of therapeutic value in the treatment of pulmonary carcinoma.

Aged↗
PubMed1979

Role of peripheral tissue receptors in stimulation of ventilation by 2,4-dinitrophenol.

Previous workers have demonstrated that hindlimb receptors can mediate some portion of the increase in VE elicited by 2,4-dinitrophenol (DNP). Liang and Hood have recently demonstrated that these hindlimb receptors communicate with the respiratory center via afferent pathways of the lumbar spinal cord. Accordingly, to determine the quantitative contribution of these hindlimb receptors to increases in VE elicited by DNP (4 mg/kg), we compared two groups of animals with respect to ventilatory, metabolic, and thermal responses elicited by this drug. Group I animals underwent complete transection of the spinal cord at the first lumbar level, whereas the spinal cord in Group II animals remained intact. Our results indicate that Group I and Group II animals did not differ with respect to increases in VE, VO2, and rectal temperature elicited by DNP. These results suggest that hindlimb receptors do not play an obligatory role in mediating increases in VE elicited by DNP. Therefore, these observations raise the possibility that multiple afferent pathways may exist for stimulation of VE by DNP.

Animals↗
PubMed1976

The effect of L-tryptophan on spinal cord C-fiber reflexes.

C-fiber reflex were recorded from an ipsilateral S1 ventral root in the acute decerebrate spinal (T10) cat after stimulation of the superficial peroneal nerve. L-Tryptophan, infused in a dose of 150 mg/kg, increased the C-fiber reflex to 210% (S.E.M. +/- 30.1%) of control. This effect was antagonized by cyproheptadine, 0.5 mg/kg. L-Tryptophan increased the C-fiber reflex to 176% (S.E.M. +/- 13.0%) of control after p-chlorophenylalanine pretreatment. Pretreatment of the cats with the decarboxylase inhibitor alpha-methyldopa, 100 mg/kg, 30 minutes before infusion, antagonized the facilitatory effects of L-Tryptophan. L-Tryptophan, 150 mg/kg, had no effect on the monosynaptic or short latency polysynaptic reflexes. 5-Hydroxytryptophan, 20 mg/kg, had erratic effects on the C-fiber reflex producing both facilitation and depression which were not statistically significant. The recovery of tryptamine from brain perfusates, after perfusion of the anterior cerebellum and pons, with a modified Gaddum push-pull cannula, decreased across time. L-Tryptophan caused a slight increase in tryptamine release which was not statistically significant, whereas in cats pretreated with p-chlorophenyl alanine, a significant increase in tryptamine release was seen.

5-Hydroxytryptophan↗
PubMed1979

Cardiovascular control in recently injured tetraplegics in spinal shock.

Cardiovascular control was studied in five tetraplegic patients with physiologically complete cervical spinal cord transections. All had been injured less than two weeks previously and were in spinal shock. Blood pressure, heart rate, and plasma noradrenaline and adrenaline were measured at rest and during and after bladder stimulation and application of cold stimuli to skin below the level of the lesion. In three patients the cardiovascular responses to intravenously infused 1-noradrenaline and to the Valsalva manoeuvre were recorded. Measurements were also made in six chronic tetraplegic patients (in whom reflex spinal cord activity had returned) at rest, and during and after bladder stimulation, and in six normal subjects at rest. Average resting blood pressure in the recently injured tetraplegics was 130/57 (mean 81) mmHg, in the chronic tetraplegics 107/55 (mean 73) mmHg and in normal subjects 122/82 (mean 95) mmHg. Average resting heart rate was 64, 73 and 77 beats/min in the three groups respectively. Resting plasma noradrenaline and adrenaline levels in both the recently injured and chronic tetraplegics were lower than than in normal subjects. In the recently injured tetraplegics bladder stimulation caused minimal changes in blood pressure, heart rate and plasma noradrenaline and adrenaline levels. In the chronic tetraplegics similar stimulation caused marked hypertension, bradycardia and elevation in plasma noradrenaline but not adrenaline levels. Cold stimuli in the recently injured tetraplegics did not change blood pressure or heart rate. In the recently injured tetraplegics intravenous infusion of 1-noradrenaline resulted in greater elevation in blood pressure than normal. There was a decrease in heart rate. One patient was able to perform the Valsalva manoeuvre. His blood pressure responses were consistenly abnormal ('blocked' Valsalva).

Adolescent↗
PubMedDate not supplied

[Scanning the subarachnoid space of the spinal cord following endolumbar and cisternal administration of colloid solutions of radioisotopes].

The patency of the subarachnoid space of the spinal cord was studied by means of radioisotopes in 82 patients, among whom 18 had tumors of the spinal cord, 22 had herniation of the intervertebral disk, 18 had complicated fractures of the spine, and 11 had inflammatory diseases of the spinal cord and its meninges. Colloidal solutions of 198Au, 111In, and 131I were used for endolumbar and cisternal infusion. Scanning of the vertebral canal provides for the diagnosis of the level, degree, and extent of its compression caused by various vertebro-medullary pathologic conditions. The method is sparing, minimum doses of isotopes are used, and no complications are produced.

Arachnoiditis↗
PubMed1977

[Radiation myelopathy-two cases with unusual development (author transl)].

This is a report of two women who experienced radiation myelopathy 2,5 and 9 months after telecobalt radiation. Tetraplegia and paralysis of the inspiratory muscles developed rapidly in the first case whereas in the second case the paralysis and the initial Brown-Sequard syndrome improved after treatment with corticosteroids and infusion of Rheomacrodex and Sorbit. It should be stressed that in both cases the radiation stress on the spinal cord was under the limit of tolerance of 3300 to 4000 R. The differential diagnosis of radiation myelopathy from spinal metastasis is most important because the treatment is different for each conditions.

Cobalt Radioisotopes↗
PubMed1978

Spinal cord compression and blood flow. I. The effect of raised cerebrospinal fluid pressure on spinal cord blood flow.

The effect of cerebrospinal fluid pressure (CSFP) on spinal cord blood flow (SCBF), measured by the hydrogen clearance technique, was studied in dogs. CSFP was altered by the infusion of mock CSF into the lumbar subarachnoid space. Occluding snares at T-13 limited the effect of raised pressure on the brain. As the perfusion pressure was reduced when the CSFP was increased, flow remained constant up to a perfusion pressure of approximately 50 mm Hg. Below this value, flow decreased with decreasing perfusion pressure. Normal flow values could be reestablished even at a raised CSFP if the perfusion pressure was increased by raising the arterial blood pressure. Rapid reduction of CSFP was accompanied by reactive hyperemia. The autoregulation of flow down to a perfusion pressure of 50 mm Hg was due to progressive decrease in vascular resistance. Carbon dioxide-responsiveness of the vessels was decreased markedly as the perfusion pressure was reduced.

Animals↗
PubMed1978

Hypotensive anesthesia for spinal fusion with sodium nitroprusside.

Deliberate induced hypotension for spinal fusion has been used in the past, but a search for better techniques continues. The authors used sodium nitroprusside by intravenous infusion to reduce the mean arterial pressure from 72 to 42 torr in 10 cases. This degree of hypotension provided an optimal surgical field and maintained adequate tissue perfusion as demonstrated by arterial oxygen tensions greater than 600 torr, no development of base deficit, and continuous urinary excretion. There were no complications related to hypotension. None of the patients received blood transfusions, whereas in the past, 2000 ml blood was usually required for this procedure.

Adult↗
PubMed1978

Catheter dislodgement: a cause of failure of intraarterial vasopressin infusions to control gastrointestinal bleeding.

Catheter dislodgement is a major cause of technical failures in intraarterial vasopressin therapy for gastrointestinal bleeding. Ten such cases were observed in the past five years. In seven patients catheter dislodgement led to recurrent bleeding during vasopressin infusion. In one patient aortic infusion of vasopressin caused recurrent bleeding and reversible acrocyanosis of the feet, and in two patients vasopressin infusion into the left renal artery resulted in chest pain and hematuria. Catheter dislodgement should be suspected if bleeding that was initially controlled recurs during vasopressin infusion.

Adolescent↗
PubMedDate not supplied

Recirculatory spinal subarachnoid perfusions in dogs: a method for determining CSF dynamics under non-steady state conditions.

Open-ended ventriculocisternal perfusion techniques for determining cerebrospinal fluid production and absorption rates are severely restricted by the absolute requirement that steady state conditions be present. A new closed recirculatory spinal perfusion technique is described. Because steady state equilibrium is not necessary, numerous determinations at multiple intracranial pressures or under varied experimental conditions are possible within relatively brief perfusion periods. Cerebrospinal fluid (CSF) and nondiffusible albumin tracer are rapidly recirculated through the spinal subarachnoid space in a cephalad direction. The concentration of fluorescein-tagged albumin is continuously monitored as the CSF is circulated through a fluorometric flow cell. Measured continuously, intracranial pressure (ICP) is regulated by changing the volume of the external perfusion circuit with a syringe pump connected in series to the recirculatory spinal perfusion. CSF formation and absorption rates are calculated from measurements of albumin concentration, concentration changes with time, ICP, syringe pump infusion rate, and the external perfusion circuit volume. In dogs, data can be collected after only 45 minutes for mixing; perfusions at four or five intracranial pressures in addition to normal resting pressure can be completed within 2 to 3 hours. The data from 15 perfusions in 14 dogs are presented. The method provides normal resting pressure values of CSF production and absorption consistent with those values in the literature determined by traditional ventriculocisternal perfusion techniques. Determinations at multiple intracranial pressures suggest a proportional relationship between absorption and ICP. No consistent acute change in CSF formation with pressures to 50 mm Hg can be inferred from these data.

Animals↗
PubMed1977

A primate model for study of methotrexate pharmacokinetics in the central nervous system.

A new technique enabling repetitive sampling of cerebrospinal fluid (CSF) in unanesthetized rhesus monkeys was developed to study the pharmacokinetics of methotrexate (MTX) in the CSF. CSF and plasma MTX levels were monitored following intraventricular and intravenous MTX administration. CSF and plasma MTX disappearance curves in the monkey were virtually identical to curves generated in humans, suggesting that the mechanisms of transport between the CSF and plasma compartments are similar in both species. These observations validate this experimental primate model and indicate its potential application to the pharmacological study of CNS chemotherapeutic agents in man.

Animals↗