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Biomedical subjects

J Ransohoff

Publications and source records attributed to J Ransohoff.

At least 91 records · Page 5Linked to original sources

Early surgical management of acute spinal cord injury.

Acute surgical decompression accompanied by stabilization and fusion is a safe procedure in patients with spinal cord injury. No patient was made worse by surgery. Patients with partial preservation of function and myelographic defects, i.e., surgical candidates, made better recoveries than those with normal myelograms who were, therefore, not operated upon. These results probably signify greater intrinsic cord damage in the nonsurgical group, but confirm the safety of surgery. We doubt the value of decompression for swollen cords except where there are hematomas. The treatment of cord swelling and ischemia will depend on improved pharmacological regimens.

Adult↗

Visual evoked potentials in chiasmal gliomas in four adults.

Visual evoked potentials (VEPs) were recorded from four patients with surgically verified chiasmal gliomas. Despite good visual acuity, 6/12(20/40) or better in each eye, these patients showed substantially reduced VEP amplitudes to a diffuse flash stimulus and hardly detectable responses to a highly textured checkerboard-pattern stimulus. The dissociation between evoked electrical activity and visual acuity is noteworthy; this differs from previously reported findings in patients with extrinsic compressing lesions of the chiasm or with lesions of demyelinating disease, which usually reduce VEP amplitude and increase conduction time in rough proportion to a loss of visual acuity.

Adult↗

Loss of essential membrane lipids and ascorbic acid from rat brain following cryogenic injury and protection by methylprednisolone.

Previous work has shown that unsaturated fatty acid components of model membrane phospholipids in vitro, damaged via a free radical mechanism, are protected by the presence of cholesterol in these membranes. The participation of these membrane lipids in the pathogenesis of traumatic injury to brain was studied in vivo using the Klatzo method of cryogenic injury in rats. Increased edema 4 hr after cryogenic injury was noted on the lesioned side. Total cerebral cholesterol was decreased significantly in the lesioned hemispheres 10 hr following injury. In lesioned animals pretreated and post-treated with methylprednisolone, there were no significant differences in the cholesterol levels. Arachidonic acid isolated from total membrane phospholipids was significantly reduced on the injured side 24 hr after injury, but not before. Other fatty acids were not significantly affected. Methylprednisolone treatment prevented the decrease in arachidonic acid. Animals that had received a cold injury had significant decreases in ascorbic acid levels after 4 hr on the lesioned side of the brain. This decrease was significantly ameliorated by corticosteroid administration. These results support the hypothesis that the protective effect of corticosteroids in cryogenic cerebral trauma may be due to antioxidant protection of major cell membrane lipid components such as cholesterol and phospholipids.

Animals↗

Acute physiological effects of ultrasonic vibrations on nervous tissue.

We investigated the acute effects of ultrasonically induced lesions on action potential conduction and blood flow in nervous tissues. A Cavitron ultrasonic surgical aspirator (CUSA) was used to emulsify small areas of cat thoracic spinal cord while hydrogen clearance, somatosensory evoked potentials, and vestibulospinal evoked potentials wee monitored. In addition, we examined the effect of direct and indirect application of the vibrating probe on rat sciatic nerves. The CUSA created localized lesions of the spinal cord, sparing the function and blood flow of immediately adjacent white structures. Histological studies revealed a sharp demarcation of the lesion sites with little morphological evidence of tissue injury beyond the borders of the lesions. The rat sciatic nerve experiments showed that, as long as the probe tip did not touch the nerve, ultrasonic vibrations had little effect on the nerve. These results suggest that the destructive effects of the ultrasonic vibrating probe are limited to a small volume at the probe tip. We conclude that, at low power levels sufficient to cause tissue emulsification at the probe tip, the CUSA does not acutely affect the function of nearby white matter. However, our results may not be extendable to higher intensity levels and do not rule out chronic effects.

Action Potentials↗

Intraspinal localization of the somatosensory evoked potential.

Somatosensory evoked potentials (SEPs) are used widely for monitoring neurophysiological function in experimental spinal injury. Yet the spinal pathways for SEP conduction remain unclear. Consequently, we sought to define specific changes in the SEP after interruption of selected spinal pathways. We activated cortical SEPs with sciatic nerve stimulation in 11 anesthetized (25 mg of pentobarbital per kg) cats after a multilevel thoracic laminectomy. The most consistent wave from component was an initial positivity (IP) at a 17- to 19-ms onset latency. We then used a Cavitron ultrasonic surgical aspirator to interrupt specific spinal pathways. A unilateral dorsal column lesion abolished the ipsilateral IP, but did not affect conduction in the contralateral column. Bilateral dorsal column lesions obliterated the IP, but sometimes left some longer latency components. Interruption of all but the ventral columns abolished the SEPs. When we interrupted all spinal pathways but the dorsal columns, an intact IP remained. In fact, a distinct IP was conducted through a single dorsal column after the division of all other spinal cord pathways. We concluded that, in the barbiturate-anesthetized cat: (a) the most consistent SEP wave form is an initial positivity at a 17- to 19-ms onset latency, (b) the integrity of the dorsal columns is both necessary and sufficient to conduct a normal-appearing IP component of the SEP, (c) the lateral columns may carry some longer latency component of the SEP, (d) the ventral columns carry no component of the SEP, and (e) bilateral recording may be useful for detecting asymmetry of injury.

Animals↗

Gastrointestinal bleeding in patients with spinal cord trauma. Effects of steroids, cimetidine, and mini-dose heparin.

The frequency and degree of gastrointestinal (GI) bleeding were examined in 131 patients with spinal cord injuries. All patients were randomly assigned to either high- or low-dose steroid regimens and some form of GI prophylaxis. The latter consisted of antacids alone or antacids supplemented with cimetidine when this medication became available. Segments of the population were treated with mini-dose or full-dose heparin. The incidence and degree of GI bleeding did not appear to be affected by steroid dose level, regimen of prophylaxis, or mini-dose heparin. Only full heparinization was found to significantly increase bleeding. These results place in question the benefits of adding cimetidine to antacids as a prophylactic atreatment in patients with no history of ulcer.

Adrenal Cortex Hormones↗

Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery.

Within three weeks of definitive surgical intervention, 467 patients with histologically proved malignant glioma were randomized to receive one of four treatment regimens: semustine (MeCCNU), radiotherapy, carmustine (BCNU) plus radiotherapy, or semustine plus radiotherapy. We analyzed the data for the total randomized population and for the 358 patients in whom the initial protocol specifications were met (the valid study group). Observed toxicity included acceptable skin reactions secondary to radiotherapy and reversible leukopenia and thrombocytopenia due to chemotherapy. Radiotherapy used alone or in combination with a nitrosourea significantly improved survival in comparison with semustine alone. The group receiving carmustine plus radiotherapy had the best survival, but the difference in survival between the groups receiving carmustine plus radiotherapy and semustine plus radiotherapy was not statistically significant. The combination of carmustine plus radiotherapy produced a modest benefit in long-term (18-month) survival as compared with radiotherapy alone, although the difference between survival curves was not significiant at the 0.05 level. This study suggests that it is best to use radiotherapy in the post-surgical treatment of malignant glioma and to continue the search for an effective chemotherapeutic regimen to use in addition to radiotherapy.

Aged↗

Tumor-specific antigens.

Based on autologous serological typing of cultured astrocytoma cells from 30 patients, three classes of surface antigens have been defined. Class I antigens are restricted to autologous astrocytoma cells. Class II antigens are shared by autologous as well as certain allogeneic tumors, but are not detected on normal cells. Class III antigens are not tumor-specific and are found on both normal and malignant cells. This analysis of human astrocytoma, with the recognition of three classes of surface antigens recognized by autologous sera, resembles the results of autologous typing of human malignant melanoma, acute leukemia, and renal carcinoma.

Antigens, Neoplasm↗

Unsymmetrical alkyl aryl thiourea compounds for use as cerebral blood flow tracers.

The synthesis and characterization of an homologous series of inert nonvolatile 14C-labeled unsymmetrical alkyl aryl thiourea compounds is described for their use as regional blood flow (rCBF) tracers employing autoradiographic procedures. In alert normocapnic rats the single-pass extraction values into brain for these thioureas were found to be dependent on their respective lipid solubilities ranging from 0.497 for 1-methyl-3-phenylthiourea to 0.730 for 1-butyl-3-phenylthiourea. The commonly used rCBF tracers [14C]antipyrine and [14C]iodoantipyrine had single-pass extraction values of 0.451 and 0.553, respectively. The single-pass extraction value for n-butanol was found to be the same as that for 1-butyl-3-phenylthiourea indicating that both n-butanol and 1-butyl-3-phenylthiourea are mildly diffusion limited at normal rates of flow in rat brain. Since 1-butyl-3-phenylthiourea diffused most readily into rat brain it was chosen as a potentially valuable rCBF tracer. Its brain-blood partition coefficient was found to be 1.09. The plasma distribution of this thiourea in blood varied inversely with the hematocrit, and the compound was freely exchangeable between plasma and erythrocytes. Employing 1-butyl-3-phenylthiourea to measure rCBF and its empirically derived brain extraction values the following flow rates in normocapnic rats were found: 3.2 ml . g-1 . min-1 for cochlear nucleus: 3.0 for inferior colliculus; 2.5 for medical geniculate; 1.9 for pontine gray and hypothalamus; 1.7 for caudate and cerebral cortex; and 1.2 for cerebellar gray and 0.41-0.50 for white matter structures. It was concluded from these studies that 1-butyl-3-phenylthiourea is more advantageous than iodoantipyrine for measuring rCBF, especially in those areas that possess very rapid rates of flow.

Animals↗

Delayed cauda equina reconstruction in meningomyelocele.

Infants afflicted with meningomyelocele are paralyzed as a result of physiologic disconnection of the neural plate from the spinal cord. Intact neural elements within the placode often maintain segmental reflex innervation of paralyzed lower extremity muscles. It was hypothesized that bridging this central peripheral gap with viable intercostal nerves would restore limited voluntary movement to paralyzed muscles. The surgical technique and initial results are the subject of this report.

Cauda Equina↗

Vestibulospinal monitoring in experimental spinal trauma.

Vestibulospinal tract function was monitored in experimental contusion of the spinal cord in cats, and compared with somatosensory cortical evoked potentials. Both white and gray matter portions of the vestibular and somatosensory pathways were evaluated in cord injuries at T-7 and L-4. Severe contusions of 20 gm-20 cm force impact resulted in a rapid (less than 1 second) abolition of thoracic white matter conductivity, but a somewhat slower (4 to 5 minutes) loss of lumbar gray matter responses. A paradoxical transient recovery of white matter conductivity occurred 1 to 2 hours after injury, despite eventual progression to central hemorrhagic necrosis at the contusion site. In contrast, mild contusions (20 gm-10 cm force impact) produced only a temporary loss of neuronal activity: white matter for 1 to 2 hours, and gray matter for 30 to 40 minutes. In general, vestibular and somatosensory potentials showed similar sensitivity to contusion, although the former tended to recover earlier. We conclude that contusion injury causes two types of neuronal dysfunction in spinal cord: 1) a low-threshold concussion-related loss of activity lasting 30 to 120 minutes; and 2) a higher threshold necrotic process, requiring 1 to 2 hours to develop, which apparently spreads from gray to white matter.

Animals↗

Intracranial pressure during nitroglycerin-induced hypotension.

Nitroglycerin was given intravenously to five anesthetized, hyperventilated (PaCO2 25 to 30 torr) patients during craniotomy, to facilitate surgery by creating a relatively bloodless field, and to decrease the potential need to blood transfusion. A subarachnoid screw and an indwelling radial artery catheter were inserted to monitor intracranial pressure (ICP) and mean arterial pressure (MAP). As MAP decreased from 10.4 +/- 4.0 (SE) to 69.0 +/- 1.8 torr, ICP increased from 14.2 +/- 0.7 (SEM) to 30.8 +/- 1.1 torr. Cerebral perfusion pressure decreased from 90.2 +/- 3.6 (SEM) to 38.2 +/- 2.3 torr (p < 0.0005). We attribute this nitroglycerin-induced ICP increase to capacitance vessel dilation within the relatively noncompliant cranial cavity, with subsequent cerebral blood volume increase.

Adult↗

In vitro transformation of fetal brain cells from CDF rats exposed in utero to N-ethyl-N-nitrosourea: morphologic and immunologic studies.

Inbred CDF rats received 250 mg N-ethyl-N-nitrosourea (ENU)/kg body weight in monosodium phosphate buffer (pH 5.5) during late pregnancy (18-21 days). Control rats received only buffer. One hour after ENU or buffer administration, the fetuses were delivered and fetal brain cells (FBC) were put in long-term tissue culture. Cell growth consisted of monolayers of glial, fibroblastic, and epithelial-like cells. FBC from buffer-treated rats could not be subcultured for more than 13-15 passages; only one culture was maintained up to the 26th passage. FBC from ENU-treated rats showed in vitro malignant transformation beginning at the 8th passage (100 days). Injection of these cells sc into irradiated or neonatally thymectomized syngeneic rats induced small palpable tumors that regressed completely by 15-28 days. Small nonprogressively growing subcutaneous tumors in normal rats, however, were obtained only after the 19th in vitro passage (200 days). These transformed FBC appeared highly antigenic. Tumor-associated antibody was demonmmune adherence assays. Rats immunized with irradiated malignant FBC showed rising tumor antibody titers. The antibody was absorbed by ENU-exposed FBC but not by normal fetal or adult syngeneic brain cells. We concluded that ENU-exposed cells become malignant when grown in vitro for at least 8 passages (100 days) but grow in vivo in X-irradiated or neonatally thymectomized rats only. These antigenic and tumorigenic clones may be selected in vitro, where they grow readily in the absence of immune resistance.

Animals↗