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Biomedical subjects

C H Tator

Publications and source records attributed to C H Tator.

At least 19 recordsLinked to original sources

Current concepts in the immediate management of acute spinal cord injuries.

The management of acute spinal cord injuries has changed considerably during the past 10 years owing to new information about the pathophysiology of cord trauma and new diagnostic and treatment methods. It is now known that the cord suffers not only from the immediate physical effects of trauma, but also from secondary pathologic processes, such as ischemia and edema, which are treatable in the first few hours after injury. New neuroradiologic and neurophysiological techniques, such as the recording of the somatosensory evoked potential, increase the accuracy of diagnosis and prognosis in the acute phase. Current immediate treatment includes the administration of steroids and mannitol, with careful attention to respiratory and cardiovascular homeostasis, to overcome post-traumatic ischemia and edema, and immobilization of the spine with devices such as the halo. New surgical procedures are used in selected cases to improve neurologic recovery, to provide rigid immobilization of the spine or to allow earlier mobilization of the patient. The care of spinal cord injuries in the acute phase is facilitated by multidisciplinary units.

Animals

Effect of vasodilators and myelotomy on recovery after acute spinal cord injury in rats.

The effect of papaverine, nitroprusside, or myelotomy on the recovery of spinal cord function was studied in rats after acute cord-compression injury. Spinal cord recovery was measured by a quantitative method of clinical assessment previously developed in our laboratory. Neither papaverine nor nitroprusside improved recovery of cord function. Dorsal midline myelotomy extending anteriorly as far as the central canal did not produce significant improvement (p greater than 0.05). However, when the myelotomy extended completely through the cord in the anteroposterior plane significant improvement (p less than 0.01) was obtained.

Animals

A new method for testing the force of clips for aneurysms or experimental spinal cord compression.

A new method is described for the determination of force-distance curves for aneurysm clips. A dissecting microscope with a goniometer eyepiece was used to determine the angle between the clip blades as various forces were applied to open the clip. The cosine law was then used to calculate the force-distance curves. The method allows accurate characterization of different clips and is especially useful for the early detection of clip weakening.

Aneurysm

Acute spinal cord injury: analysis of epidemiologic factors.

The authors studied the epidemiologic aspects of acute spinal cord injury in 358 patients admitted to the Toronto General and Sunnybrook hospitals between 1948 and 1973. The ages of the patients ranged from 14 to 89 years (median 32 years) and the male:female ratio was 4.5:1. The most frequent causes of injury were traffic accidents (34.4%), accidents at work (29.3%), sports-recreational injuries (15.4%) and falls at home (9.8%). Several epidemiologic factors were identified which are important for developing programs to reduce the frequency of cord injury. In particular young persons should be made more aware of the risks they run as automobile drivers and of the hazards of diving in shallow water, middle-aged workers in the construction industry are at risk of spinal cord injury from falls and elderly farmers are at risk of falling from lofts or being crushed by overturned tractors.

Accidents, Home

The effect of amphotericin B on the survival of brain-tumor-bearing mice treated with CCNU.

The membrane-active polyene, amphotericin B (AMB) has been shown to enhance or potentiate the effects of various chemotherapeutic agents against tumor cells in tissue culture. Because of the need to increase the efficacy of the nitrosoureas in brain-tumor chemotherapy, we have studied the effect of the nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), with or without AMB pretreatment. The intraperitoneal administration of 25 mg/kg of AMB 24 hours before 5, 10, 20 or 30 mg/kg of intraperitoneal CCNU did not result in a significant improvement in survival. The failure of intraperitoneal AMB to potentiate the effect of CCNU was likely a failure in drug delivery, since AMB crosses the blood-brain barrier very poorly. To circumvent the drug-delivery problem, AMB was administered intracerebrally directly into the tumor-bearing hemisphere. With 0.5 mg/kg of intracerebral AMB administered 24 hours before 10 mg/kg CCNU was given intraperitoneally, the life-span was significantly increased over the control group. The same dose of CCNU alone did not significantly increase survival. When 0.2, 0.5, or 1.0 mg/kg AMB was administered intracerebrally 24 hours before 20 mg/kg of interaperitoneal CCNU, survival was significantly increased over those groups receiving the same dose of CCNU alone. It is concluded that direct intracerebral administration of AMB enhances or potentiates the therapeutic effect of CCNU in this brain-tumor model.

Amphotericin B

Regional spinal cord blood flow in rats after severe cord trauma.

Spinal cord blood flow (SCBF) was measured in 12 albino rats following acute cord injury produced by the extradural clip compression technique. Severe injury was produced with the clip compressing the cord with a force of 180 gm for 5 minutes, an injury previously shown to produce a severe functional deficit. Regional SCBF was measured 15 minutes, 2 hours, and 24 hours after injury by the 14C-antipyrine autoradiographic technique and a scanning microscope photometer. At 15 minutes and 2 hours, white and gray matter blood flow was severely diminished, and, at 24 hours, there was only minimal improvement. Focal decreases in blood flow were seen in white and gray matter for a considerable distance proximal and distal to the site of cord trauma. Thus, it has been confirmed in this model that severe cord compression injury produces severe posttraumatic ischemia in the cord which lasts for at least 24 hours.

Animals

Somatosensory evoked potentials in acute spinal cord injury: prognostic value.

The somatosensory evoked potential is absent in patients with complete motor and sensory loss below the level of spinal cord injury. When spinal cord injury is incomplete, these alterations in potential may be elicited from stimulation of a nerve entering the cord below the level of injury. The presence of such potentials soon after injury, or their early return, and progressive normalization of the wave form are sensitive early indications of favorable prognosis. Indeed, recovery of the somatosensory evoked potentials frequently precedes major clinical improvement and may occur in advance of clinical recovery or posterior column function.

Adolescent

Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat.

The effect of duration of acute compression of the spinal cord was assessed in a new model in the rat. The spinal cord was acutely compressed for varying times by a modified aneurysm clip which produced a compression force of 180 grams. The effect of duration of compression was measured by the inclined plane method of assessing the animals' clinical performance. The results showed a linear relationship between log compression time and clinical performance. Thus, the clinical effect of acute compression of the spinal cord injury is inversely related to duration of compression time and the relationship has been precisely quantified. These results suggest that persisting compression should be relieved as soon as possible in order to improve recovery.

Acute Disease

Intraneoplastic injection of methotrexate for experimental brain-tumor chemotherapy.

The retention and distribution of tritiated methotrexate (MTX-3H) after direct intracerebral or intraneoplastic injection were studied in mice bearing subcutaneous or intracerebral ependymoblastomas. After intracerebral injection of MTX-3H in nontumor-bearing animals, a large amount of the drug was retained in the head, much more than could have been retained after systemic administration, and there was rpaid spreading of the drug through the ipsilateral hemisphere. Intraneoplastic injection of subcutaneous and intracerebral tumors produced rapid spreading of the drug through the tumors. Intially, the drug was mainly in the intersititial fluid of the tumors followed by earlier cellular uptake than was seen after intravenous injection. Even though the distribution of the drug in the intracerebral tumors was not uniform, and some intracranial tumor deposits contained less radioactivity than areas closer to the site of injection, intraneoplastic injection may have advantages for brain-tumor chemotherapy. However, further experimental study is necessary before clinical application can be recommended, especially evaluation of neurotoxicity after intracerebral, intraneopasltic injection of MTX or other chemotherapeutic agents.

Animals

Therapy of an experimental glioma with systemic or intraneoplastic methotrexate or radiation.

An intracranial mouse glioma model was used to study the effectiveness of chemotherapy with methotrexate )MTX) or radiotherapy. Maximum tolerable doses of MTX were established by toxicity studies in nontumor-bearing mice for the intraperitoneal and intracerebral routes of drug administration with and without leucovorin as an antidote. These maximum tolerable doses were then given either by the intraperitoneal route or directly into the tumor to mice bearing intracerebral tumors. The glioma model proved to be extremely useful for assessing the modalities studied, including repeated intraneoplastic injection of MTX. Dosage schedules were successfully developed for administering large amount of MTX and for preventing systemic toxicity by the administration of the antidote. Radiotherapy in single doses and 800 rads delayed the median day of death and produced several long-term survivors. Higher doses were toxic. Intraperitoneal or intraneoplastic MTX was completely ineffective as a chemotherapeutic agent for this tumor, even though very large amounts could be delivered due to the protection from systemic toxicity afforded by leucovorin. It is concluded that MTX is a poor chemotherapeutic agent for this experimental brain tumor, but that the technique of intraneoplastic administration of chemotherapeutic agents is feasible with this model system and should be studied further.

Animals

Objective clinical assessment of motor function after experimental spinal cord injury in the rat.

A new method was developed for the clinical assessment of motor function in rats after experimental spinal cord injury. The method consists of placing the animal on an inclined plane which can be adjusted to provide a slope of varying grade, and then assessing the maximum angle of the plane at which the animal can maintain its position without falling. The method was used to quantitate motor function in normal rats and in rats subjected to myelectomy, and consistently showed major differences between the two groups. The method has many positive features: the plane is easy to construct and of low cost; and the test is rapid, non-invasive, repeatable, and consistent.

Animals

Chemotherapy of an experimental glioma with nitrosoureas.

Chemotherapy experiments were performed with 2 nitro-sourea drugs in an experimental mouse brain tumor model. Cell suspensions of a transplantable mouse ependymoblastoma were injected i.c. by means of a stereotactic frame. The drugs used were 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea and were given by either i.p. or by direct intraneoplastic (i.n.) injection on the fifth day after tumor cell implantation. Injections i.n. of drugs were made with the stereotactic frame. Both drugs were highly effective in increasing the median day of death and in yielding large numbers of long-term survivors. Effectiveness was evident after i.p. or i.n. injection. However, with certain dosage schedules such as every 2 hr for 5 injections daily on 2 consecutive days, i.n. injection was more effective and less toxic than i.p. injection. The reason why repeated i.n. injections produced less toxicity than repeated i.p. injections is not definitely known but may be due to local metabolism of the drugs in the tumors and surrounding brain to a less toxic form. This is the first laboratory report of direct i.n. injection of the nitrosoureas, and the authors consider these results encouraging.

Animals

Intraneoplastic injection of CCNU for experimental brain tumor chemotherapy.

Chemotherapy experiments were performed with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in an experimental mouse brain tumor model. Cell suspensions of a transplantable mouse ependymoblastoma were injected intracerebrally by means of a stereotactic frame. CCNU was given either intraperitoneally or by direct intraneoplastic injection beginning the fifth day after tumor cell implantation. Intraneoplastic injection beginning the fifth day after tumor cell implantation. Intraneoplastic injections of drugs were made with the stereotactic frame. A single intraneoplastic injection of CCNU was found to be highly effective in increasing the median day of death and in yielding large numbers of long-term survivors. In some experiments CCNU injected into the neoplasm produced increased numbers of long-term survivors and less systemic toxicity than when injected intraperitoneally.

Animals

Review of the measurement of normal spinal cord blood flow.

The field of spinal cord blood flow (SCBF) is reviewed. The methodology currently being used to evaluate SCBF is critically analyzed. The review demonstrates that there is a paucity of reliable quantitative measurements of SCBF. The effects of arterial pCO2, pO2 and blood pressure variations as well as the effects of several pharmacological agents on SCBF are also discussed.

Animals

Review of the effect of spinal cord trama on the vessels and blood flow in the spinal cord.

The effect of spinal cord trauma on the vasculature and blood flow of the spinal cord is reviewed. Both quantitative and nonquantitative studies are critically discussed and reasons sought for some of the major controversies that have arisen. Differences in methodology, species variation, and variation in the degree and type of cord injury may all be important factors in producing the conflicting results reported in the literature. In general, it can be said that trauma has a profound effect on the vasculature and blood flow in the cord and that severe compression injury of the cord causes marked ischemia in the gray and white matter.

Animals

Regional spinal cord blood flow in primates.

Spinal cord blood flow (SCBF) was measured in the primate thoracic spinal cord using the 14C-antipyrine autoradiographic technique that allowed clear differentiation between white and gray matter blood flow. Individual SCBF values were obtained for 0.1-sq mm areas of the thoracic cord cross section. White matter blood flow was homogeneous throughout with a mean value of 10.3 +/- 0.2 ml/100 gm/min. Gray-matter flow was more variable with lower values in the dorsal horns and higher values in the central gray and anterior horns. Mean gray-matter flow was 57.6 +/- 2.3 ml/100 gm/min. Arterial pO2 was 123 +/- 2 torr, pCO2 was 40.2 +/- 0.5 torr and pH was 7.327 +/- 0,010. Mean arterial blood pressure was 113 +/- 3 mm Hg and core temperature was 36.4 degrees +/- 0.1 degrees C.

Animals