Fetal human and pig mesencephalon xenografts have equal effectiveness in behavioral restoration of damaged rat brain.
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Biomedical subjects
Publications and source records attributed to R W Rand.
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A thrombogenic microballoon was developed to overcome the problems of cerebral aneurysm rupture during microballoon inflation and incomplete aneurysm obliteration by microballoons with subsequent fatal rupture. These complications occur in about 35% of reported series with current microballoon embolization techniques. The wall of the new thrombogenic microballoon allows 80% aneurysm occlusion by inflation, thus avoiding mechanical rupture, and at the same time it produces a blood clot in the space remaining between the microballoon and the aneurysm wall. This clot undergoes fibrosis with firm adherence of the microballoon to the aneurysm wall. Experimental evidence is presented to support these conclusions. This thrombogenic microballoon system is also applicable to carotid-cavernous fistulas and arteriovenous malformations.
We present interim survival data for a group of 83 adult patients with recurrent malignant glioma treated by implanting stimulated autologous lymphocytes into the tumour bed following surgical debulking. The patients were treated 6 months or more prior to data analysis. Fifty-nine patients were male and 24 female. The mean age for the entire group was 48.4 years and the mean Karnofsky rating (KR) was 67.2. Eight of the patients had grade II tumours, 33 had grade III tumours and 42 had grade IV tumours. Statistical analysis focuses on tumour grade, KR and patient age, factors that have been shown to affect survival in previous studies. Multifactorial analyses are employed to identify interrelationships among factors related to survival. Seven patients (8%) did not respond to immunotherapy, 76 (92%) had a good initial response. Twenty-five patients (30.1%) are living and 18 (22%) have shown no evidence of recurrence. Results are evaluated in the light of those obtained in trials of other experimental therapies for recurrent malignant gliomas. It is concluded that the present protocol offers a safe and comparatively effective treatment option.
We studied brain retroperfusion in nine adult baboons. Experiments in four baboons determined techniques and the safety of retroperfusion, and experiments in three baboons determined the ability of retroperfusion to reverse cerebral ischemia. Two baboons died before retroperfusion. Arterial blood was continuously circulated by an external pumping system from one femoral artery into the intracranial sinuses through specially designed balloon-tipped catheters placed percutaneously into the sigmoid sinuses bilaterally. The balloons intermittently occluded the sinuses. Ischemia was produced by occluding the left middle cerebral artery. Standard and computed electroencephalography with topographic mapping monitored the onset and reversal of ischemia. Retroperfusion rate exceeded 50 ml/min with a mean intrasinus pressure increase of 27 (0-149) mm Hg in all seven experiments. Venograms demonstrated complete or partial filling of the superior sagittal sinus in each experiment. Four experiments without ischemia established maximal balloon occlusion cycles, retroperfusion rates, and sinus pressure changes. These four baboons were neurologically normal after retroperfusion; two had normal magnetic resonance imaging scans. Ischemic changes, detected by electroencephalography following middle cerebral artery occlusion, were reversed with retroperfusion in all three ischemia experiments. Autopsies in the seven baboons demonstrated no parenchymal hemorrhage or edema. Our results suggest that further investigation of retroperfusion, and possibly retroinfusion of agents for cerebral protection, is warranted.
Neurosurgeons have traditionally advocated the transmeatal suboccipital craniectomy as the procedure of choice in treating acoustic neuromas of all sizes. With this technique, complete tumor removal was achieved in 91% of our patients. Facial motor activity was fully preserved in 59% and it was only partially deficient in an additional 29%. Conversely, recent otological reports have proposed a more flexible attitute in which the size of the tumor dictates the form of surgical therapy. In that scheme, the universally applicable and clinically proven suboccipital craniectomy is replaced by a series of procedures (translabyrinthine, middle fossa, transsigmoidal), each of which differs in its anatomical and technical requirements. This necessity for several operations seems to stem from the failure of any particular approach either to provide adequate visualization of the entire pathological process, or to afford maximum opportunity for complete tumor removal. By employing these various techniques, total capsular removal has been generally achieved in only 71% of cases. A careful comparison and analysis of these individual procedures reaffirms the superiority of the posterior fossa approach.
In a comparative experiment, transplantation of orthotopic nerve fascicle was performed on 100 sciatic nerves between inbred, antigenically identified rats. The authors studied cellular response, macrophage reaction, connective-tissue reaction, myelination, and distal/proximal axonal ratios, but no difference could be established between allografted and autografted fascicles after 2 months. Moreover, there was no evidence of any graded rejection phenomenon dependent on differences of tissue typing. Theories for the decreased antigenic reaction of nerve fascicles are proposed.
Orthotopic whole-nerve and fascicular nerve grafts were transplanted between inbred rats with known histocompatibility antigen structure. In general, the whole sciatic nerves demonstrated a graded rejection response dependent upon the degree of tissue histocompatibility differences. The fascicular grafts, however, had evidence of greatly decreased rejection and no stigma of a graded response dependent on degree of variability of tissue typing. Limitations of the experiment are outlined, and the possible avenues of further research are briefly discussed.
Recent Russian reports have described the use of balloon occlusion in both the diagnosis and treatment of various pathological processes affecting intracranial vessels. This intraluminal approach has demonstrated successful results in vascular problems such as carotid-cavernous fistulae, arteriovenous malformations, and large inoperable aneurysms. Despite widespread interest in the neurosurgical community, the application of a similar technique in the Western hemisphere has been hindered by lack of an adequate, functional, inflatable apparatus. The authors describe their experience with the prototype of a safe, reliable, detachable balloon. Because of a unique development, the apparatus may be filled with liquid and detached from its parent catheter without subsequent leakage. In order to satisfy variable requirements, balloons are available in several sizes ranging from 0.5 to 4.0 mm in diameter. When fully inflated these devices will hold from 1 to 3 cc of fluid. The authors' study involved 18 dogs with artificially created carotid-jugular fistulae that were visualized by angiography. Under fluoroscopic control, detachment of inflated balloons on the venous side of the defect not only successfully occluded the fistulae but also preserved the arterial vasculature. X-ray films taken several weeks later failed to show any change either in size or position of the inflated devices.
A technique is outlined for retraction of tumors under the operating microscope using the microcyoprobe. The method depends on temperatures settings in the--20 degrees to--30 degrees C range to produce a small ice bond uniting tumor and cryoprobe. No attempt is made to create a solid frozen tumor. The locally avascular field and retraction provided ideal circumstances for microdissection. Examples of this approach are outlined with case summaries for spinal cord ependymoma and hemangioblastoma.
A preliminary experiment was devised to delineate the specificity of nerve allograft rejection. Skin grafts were performed between inbred strains of Fisher, AgB1, and Buffalo, AgB6, rats to determine the time required for a first set rejection, which occurred at day 9. Skin grafts also were performed two weeks after orthotopic placement of whole nerve or fascicular grafts. The rats that had previously been exposed to whole nerve showed skin graft rejection at six days, while those exposed to nerve fascicle demonstrated skin graft rejection at seven days. Fascicular whole nerve allografts and autografts were compared histologically at seven, 12, 19 and 28 days after grafting. The whole nerve allograft consistently showed gross and microscopic evidence of lymphocytic infiltration consistent with rejection involving the perineural connective tissues. Antigens obviously are present in sufficient levels in both the nerve and surrounding connective tissue, but at least, theoretically, there are some advantages to the use of fascicles versus the whole nerve.
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Serum growth hormone (GH) responses to thyrotropin-releasing hormone (TRH) were evaluated in 14 patients with acromegaly following treatment with thyroid hormones. After an initial TRH test, seven patients received L-triiodothyronine, 100 mug daily for seven days; the GH response to TRH was not significantly altered by this treatment. Similar findings were noted in two acromegalic subjects who were tested with TRH before and after longer periods of administration of L-thyroxine. Four of five additional subjects with acromegaly who had received replacement doses of thyroid hormones for an average of 6.6 yr demonstrated GH responses to TRH which were similar to those seen in subjects not receiving thyroid hormones. Acute or long-term administration of replacement doses of thyroid hormones seems to have minimal effect on the GH response to TRH in acromegaly.
Between 1963 and 1974, 54 patients with acromegaly (28 men and 26 women) ranging in age from 23 to 61 years were evaluated. Each patient underwent thorough preperative neurological, roentgenographic, and endocrinological surveys; most demonstrated mild-to-severe abnormalities in growth hormone immunoassay and oral glucose tolerance. Of those who underwent stereotaxic cryohypophysectomy, approximately 80% were considered to have a beneficial result. The efficacy of this form of therapy was judged on the basis of: 1) significant overall clinical improvement and regression of acromegalic features; 2) improvement in the glucose tolerance curve; and 3) a fall of serum growth hormone below 10 ng/ml. Complications including rhinorrhea, meningitis, and hemorrhage occurred in only a small number of cases. A comparison is made between this technique and other, including craniotomy, radiotherapy, and transnasal transsphenoidal hypophysectomy. The efficacy, low morbidity, and the ease with which the procedure may be performed make this our treatment of choice when dealing with growth-hormone-producing pituitary adenomas with no suprasellar extension.
Simple lacerations of dog anterior tibial nerves were repaired utilizing fascicular interfascicular, and epineural suture techniques. Two months following repair, the involved regions of the nerve were removed and stained with hematoxylin and eosin, Weil, Bielschowsky, and Masson trichrome stains. An independent, unbiased observer rated proximal and distal myelin, connective tissue responses, and proximal to distal axon counts. The proportion of proximal to distal axons revealed no significant difference between fascicular (77%) and epineural (67%) neurorrhaphy, but showed a significant beneficial effect of fascicular suture to the interfascicular (52%) repair (significance at less than 0.02). Masson stain revealed dense connective tissue responses, but the axon counts were adversely affected only when the separate fascicles showed internal disruption by connective tissue. In general, distal myelinization was mildly superior with the fascicular neurorrhaphy technique. It appears that in simple lacerations in nerves which are repaired via direct end-to-end suture, there is no significant advantages to fascicular over epineural repair; however, there is a definite deleterious effect of interfascicular neurorrhaphy. The theoretical and technical implications of these findings are discussed.
Cerebrospinal rhinorrhea is an uncommon complication of head trauma or of diverse types of intracranial diseases. Because of the risk of meningitis, this condition warrants immediate attention. If the leak fails to stop spontaneously in a short time, the precise site of the leak must be ascertained and surgical repair attempted. For the past 50 years craniotomy has been the principal operative approach; however, this method carries the risk of significant morbidity and protracted hospital stays, as well as a disappointing incidence of persistent leak. During the past decade extracranial operations for dural repair have been devised, and experience in the management of patients by a variety of such procedures illustrates the success of these operations.
A large retroperitoneal hemangiopericytoma was resected successfully with the aid of preoperative control of the blood supply of the lesion with percutaneous intra-arterial gelfoam and ferromagnetic silicone embolization. We believe that this resection would not have been possible without this adjuvant technique. Future application of this combined technique will enable more aggressive surgical intervention in unresectable vascular tumors and arteriovenous malformations.
Numerous causes of peripheral facial nerve paralyses have been described; however, none has satisfactorily explained the genesis of the most common type of paralysis, Bell's palsy. Two patients undergoing an experimental embolization of vascular intracranial tumors suffered a total peripheral facial nerve paralysis when occlusion of the middle meningeal artery had been accomplished. It is speculated that this paralysis resulted from ischemia of the horizontal portion of the facial nerve, an observation that has not previously been described and that might be applicable as well to the etiology of Bell's palsy.