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Biomedical subjects

M Salcman

Publications and source records attributed to M Salcman.

At least 37 records · Page 2Linked to original sources

The use of anterior Caspar plate fixation in acute cervical spine injury.

Optimal management of cervical cord injury in the presence of documented instability and/or compression of neural elements remains a controversial topic. Surgery and internal stabilization of cervical spine fracture/dislocations are effective and well accepted, but controversy exists on the relative merits of the anterior versus the posterior approach as well as the optimal timing of surgical intervention. We report our experience with the Caspar technique and instrumentation for anterior stabilization in 54 patients for acute cervical spine injury. Our series consists of 38 male and 16 female patients whose ages ranged from 16 to 68 years, with a mean age of 29.2 years. Thirty-two of these patients had complete neurological sensory/motor deficits at the time of presentation, eight were neurologically intact, and 14 had preservation of some motor and sensory function. All 54 patients had radiographic evidence of posterior instability as well as anterior disruption of either a vertebral body or intervertebral disk. We found that "early" intervention (less than 24 hours after injury) was performed frequently in the neurologically compromised patients. Twelve of the 22 patients undergoing surgery less than 24 hours after admission regained significant neurological function, with 13 of 22 developing postoperative complications. In the "delayed" group (surgery more than 24 hours after injury, mean 14.3 days), 14 patients experienced postoperative complications, with 15 of 24 demonstrating neurological improvement. The eight patients who were intact did uniformly well. There was no mortality during the follow-up. All 54 patients showed a solid fusion (clinically and radiologically) within 6 months of surgery. In two cases the plates had to be removed, without risking the fusion. Our experience suggests that although anterior cervical fusion and Caspar plating remain appropriate for patients with documented anterior compromise of the canal, it should not substitute for more traditional posterior stabilization procedures. Because this route has the potential for more serious complications, it should be reserved for the cases in which anterior decompression is deemed necessary or posterior fusion was unsuccessful. With appropriate selection of patients, no adverse effect of early surgery was demonstrated. In fact, neurologically compromised patients had the benefits of increased ease of patient care and early transfer to rehabilitation.

Adolescent↗

In vitro response of human glioblastoma and canine glioma cells to hyperthermia, radiation, and chemotherapy.

Little is known about the sensitivity of human glioblastoma cells to hyperthermia alone and in combination with other therapies. We carried out in vitro cell survival studies on the human glioblastoma cell line U-87MG and our model canine glioma canine brain tumor (CBT) cells after multimodality treatment. Ionizing radiation was administered to flasks of cells in logarithmic growth at 500 rads (5 Gy) with consecutive treatment by hyperthermia, 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), or cisplatin. Cells were treated with single doses of BCNU at 5 microM with sequentially added radiation or hyperthermia and at 1 to 2 micrograms/ml of cisplatin with hyperthermia. Hyperthermia was administered in a precision controlled water bath at 44 degrees C for 30 minutes in combination with chemotherapy or radiation. In general, the sensitivity of U-87MG and CBT cells was similar for all test regimens. For example, colony formation efficiency decreased by 64% in CBT cells and by 64.4% in U-87MG cells after hyperthermia alone at 44 degrees C for 60 minutes. All combinations of BCNU, hyperthermia, and radiation administered in vitro produced enhanced cell killing, but the effects of multiple modalities were generally additive in both cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intravenous recombinant interferon beta in patients with recurrent malignant gliomas: a phase I/II study.

A multicenter phase I/II trial of a human recombinant interferon beta (Betaseron; Triton Biosciences, Alameda, CA) was conducted in patients with recurrent glioblastoma and anaplastic astrocytoma in six centers between 1986 and 1988. Betaseron was given intravenously three times per week, starting at 90 x 10(6) IU per dose and escalating by 90 x 10(6) IU every 2 weeks up to a maximum dose of 540 x 10(6) per treatment. All patients had failed prior radiotherapy, and most had failed one or more courses of chemotherapy. Of the 72 patients entered into the protocol, 65 were considered assessable. Of 65 patients, 41 had glioblastoma, and 24 had anaplastic astrocytoma. Of the 65 assessable patients, 15 (23%) had an objective response (R), and 18 (28%) had stable disease (S), with a combined R and S rate of 51%. The Kaplan-Meier median time to progression was 24 weeks for the responders, 10 weeks for the nonresponders, and 23 weeks for the whole group. These results suggest that Betaseron has definite activity in recurrent gliomas, with an R + S rate of 51%. The maximum-tolerated dose (MTD) is between 180 and 360 x 10(6) IU, with neurotoxicity being the most troublesome toxicity at higher doses. Two patients died of treatment-related complication. Since most responders showed responses at the 180 x 10(6 IU dose range, further studies using a lower dose of Betaseron aimed at decreasing toxicity and allowing chronic maintenance therapy are merited.

Adult↗

Nonoccupational risk indicators of glioblastoma in adults.

A case-control study of brain tumor was conducted in collaborating hospitals in Boston, Providence, and Baltimore. Cases were 160 consecutive patients being treated for glioblastoma, grade 3 or 4 astrocytoma, or anaplastic astrocytoma. Controls were 128 healthy persons identified among the case's friends. A complex self-administered questionnaire was used to assess exposure to factors of interest. There was some evidence that glioblastoma is associated with a decreased susceptibility to allergies, a finding that may call attention to the involvement of immunologic disturbances in brain tumors. Our data are not supportive of previous reports of an association between brain tumors and exposure to pets or farm environment, family history of CNS malignancies or other neurologic conditions, or irradiation to the head. We did not find any evidence for an association with life-style characteristics such as cigarette smoking, alcohol consumption, use of drugs of any kind, or dietary intake of cured or smoked meat or fish.

Adolescent↗

Aneurysms of the posterior inferior cerebellar artery-vertebral artery complex: variations on a theme.

Aneurysms of the posterior inferior cerebellar artery-vertebral artery complex are relatively uncommon lesions. They include aneurysms at the origin of the posterior inferior cerebellar artery (PICA-VA), aneurysms on the distal artery (PICA) and aneurysms at the junction of the vertebral and basilar arteries (VA-BA). We have had the opportunity to treat 17 patients and study the radiological records of 9 additional patients in the past 8 years. The aneurysms ranged in size from 3 to 30 mm, with mean values of 10.6, 7.3, and 9 mm for PICA-VA lesions, distal PICA lesions, and VA-BA lesions, respectively. Three of the 4 VA-BA aneurysms were located at the midline, and the mean distance of the PICA-VA aneurysms from the midline was 7.6 to 9.4 mm; 2 aneurysms crossed the midline from their parent VA. The aneurysms were located slightly more often on the left side (left:right ratio, 1:2), were found more frequently in women (2.25:1), and occurred at a mean age of 50 years. Ten aneurysms at the origin of the PICA and 4 VA-BA aneurysms were treated via a lateral suboccipital craniectomy; 3 distal PICA aneurysms were exposed by a midline craniectomy. Surgery was carried out acutely in 5 patients. Tortuousness of the VA required contralateral approaches in 2 patients, an exploratory craniectomy in 1 patient, and an approach toward the dome of 1 patient with a VA-BA aneurysm. Morbidity was primarily due to cranial nerve dysfunction. There were no perioperative deaths. These aneurysms can easily be missed on initial radiographic examination; one appeared only on the second study, one was seen to grow over 16 days, and one was discovered at the level of C1 extracranially. Our radiographic and surgical approach to the treatment of these lesions is presented.

Adult↗

Malignant glioma management.

The many options neurologic surgeons have for the treatment of malignant gliomas are reviewed. Although virtually no malignant gliomal tumor can be cured by surgical resection alone, in the majority of cases, some combination of open resection or stereotactic surgery can produce a diagnosis, ameliorate symptoms, decrease the intracranial pressure, improve neurologic status, remove most of the tumor, and deliver other therapeutic agents. The techniques of both open resection and stereotactic surgery are discussed.

Brain Neoplasms↗

Allografts of CNS tissue possess a blood-brain barrier. I. Grafts of medial preoptic area in hypogonadal mice.

This study represents the first part of a three-part investigation of blood vessels supplying CNS tissue transplanted within the brains of adult mammalian hosts. The results emphasize that blood vessels in solid CNS grafts contribute a blood-brain barrier to that of the host. Neurosecretory cells in basal forebrain grafts placed intraventricularly on the dorsal surface of the host median eminence, a neurosecretory site containing fenestrated blood vessels, do not stimulate similar blood vessels to inhabit the transplanted tissue. Solid grafts of the medial preoptic area containing neurons that synthesize and secrete gonadotropic hormone-releasing hormone (GnRH) were obtained from AKR mice and placed into the third cerebral ventricle of hypogonadal (HPG) mice genetically incapable of synthesizing GnRH. GnRH neurons in the allografts were confirmed immunohistochemically. Blood vessels supplying the host median eminence and the allograft at 10 days to 3 months post-transplantation were analyzed with peroxidase cytochemistry applied in three ways: to HPG mice injected systemically with native horseradish peroxidase; to HPG mice infused into the aorta with peroxidase subsequent to perfusion fixation; and to HPG mice brains fixed by immersion and incubated for endogenous peroxidase activity in red cells retained within blood vessels. The median eminence of the HPG mouse was innervated by GnRH neurons residing within the graft, and blood vessels traversing the median eminence-allograft interface were seen rarely. The allografts contained no fenestrated endothelia, and no extravasations of blood-borne HRP were related directly to leaky blood vessels supplying the grafted tissue. Endothelial cells throughout the CNS grafts were similar morphologically to blood-brain barrier endothelia; they were nonfenestrated, exhibited interendothelial tight junctional complexes and an endomembrane system of organelles, and they endocytosed blood-borne HRP that eventually was sequestered within dense body lysosomes. The results support the belief that blood vessels supplying CNS tissue transplanted to a host brain manifest endothelial characteristics identical to those of the tissue in normal life and to those of the host CNS.

Animals↗

Technical aids for the flexible use of the Leksell stereotactic system.

As part of a multimodality therapy program for intracranial tumours, 105 stereotactic and implant procedures have been carried out utilizing the CT-compatible Leksell stereotactic system. In the iridium implant series, 86 catheters have been implanted for an average of 3.6 targets per patient. There have been no deaths or missed targets and only two incidential haemorrhages detected. In order to facilitate the reliability, safety and speed of multiple catheter insertion, several techniques have been developed including: (a) a standardized single-length catheter and flange system; (b) a ceramic catheter for microwave hyperthermia; (c) a mnemonic card for ease of calculation; (d) a radiation shield for nursing; (e) a stereotactic drill and surgical approaches to far lateral and posterior fossa targets. Principles for the use of these technical aids are discussed.

Brain Neoplasms↗

Alumina ceramic as a biomaterial for use in afterloading radiation catheters for hyperthermia.

A major technical challenge to the use of interstitial hyperthermia in malignant brain tumors is the production of a well-defined, uniform hyperthermal field. In theory, A 915-MHz microwave antenna should allow fewer antennas to be used and cause less mechanical brain damage; however, standard radiation afterloading catheters require antennas to be 12 cm long; this is clearly impractical for intracranial use. Since alumina ceramic (Al2O3) catheters permit short microwave antennas (3-5 cm in length) to function properly in neural tissue, it is important to test the biocompatibility of alumina for use in combined interstitial microwave hyperthermia and brachytherapy. A 5-mm length of alumina catheter was implanted into the brains of 15 white rats. The animals were killed at 3, 7, 14, 28, and 56 days. Histological examination revealed only minor mechanical damage and no encapsulation until 1 month; even then, the glial wall was only a few cell layers thick. Five animals received implants and were killed at similar intervals for x-ray microanalysis with the scanning electron microscope. No migration of aluminum into the brain was detected when compared with two control animals that did not receive implants and an alumina blank. Although we measured 50% attenuation of the radiation from iridium-192 sources in alumina catheters as compared with conventional ones, alumina catheters can still be used for interstitial radiation by increasing either the activity of the seeds or the duration of treatment.

Aluminum↗

Pituitary hyposecretion and hypersecretion produced by a Rathke's cleft cyst presenting as a noncystic hypothalamic mass.

A 53-year-old man presented with polydipsia, polyuria, lightheadedness on standing, and syncope. Visual field deficits suggesting left optic tract compression and pituitary dysfunction consisting of diabetes insipidus, hyperprolactinemia, and anterior pituitary insufficiency were diagnosed. On the computed tomography scan, an isodense, ring-enhancing, parasellar mass was localized primarily in the suprasellar region and also extended into the sella. It was believed that the pituitary hormone hypersecretion and hyposecretion were due to hypothalamic dysfunction from the mass which was initially believed to be a craniopharyngioma. At surgery a Rathke's cleft cyst was resected. The unusual presentation of this Rathke's cleft cyst presenting as a hypothalamic lesion is discussed.

Craniopharyngioma↗

Cerebral blood flow and the thermal properties of the brain: a preliminary analysis.

Safe and effective use of hyperthermia for the treatment of brain tumors requires precise control of the distribution of temperatures (that is, the thermal field) within the tumor and within the adjacent brain. Major influences upon the distribution of temperatures include the passive thermal properties of the brain, such as its specific heat (Cb), and the contribution of cerebral blood flow (CBF). Recently, an electrical-mechanical analog model of heat flow within the brain has been developed from which an expression for CBF has been derived: CBF = Cb/(tau rho c) where tau is the thermal decay constant, rho is the density of blood, and c is its specific heat. To test this model a series of experiments was carried out in adult dogs in which stereotaxically implanted microwave antennas operating at 2450 MHz, fluoro-optical thermometry probes, and platinum electrodes were used to simultaneously measure CBF by thermal washout and hydrogen clearance techniques. The correlation coefficient for estimates of CBF derived by the two methods in 52 paired observations was 0.89. Measurements of CBF were more reliable at increased distances from the microwave antenna, since CBF is sensitive to the degree of temperature elevation (delta T). The ratio of post-heating CBF to pre-heating CBF varies linearly with delta T and has a correlation coefficient of 0.86. When values of CBF determined by the hydrogen clearance method were employed in the above equation, it was possible to derive Cb as 0.70 +/- 0.08 cal/gm-degrees C. Use of this value for Cb in this equation produces estimates of CBF by thermal clearance that are within 10% of the values for CBF as measured by the hydrogen clearance method. It is concluded that this model of thermal flow within the brain may have heuristic value for treatment planning and that microwave antennas and fluoro-optical probes may represent a new methodology for the clinical estimation of CBF. These methods have recently been employed in patients undergoing combined hyperthermia and chemotherapy.

Animals↗

Subarachnoid hemorrhage.

Primary subarachnoid hemorrhage represents 10 percent of strokes. Aneurysm is the most common cause, accounting for 28,000 cases of hemorrhage annually in North America. Headache is the most prominent feature and heralds the moment of rupture.

Adolescent↗

Surgical management of lung cancer with solitary cerebral metastasis.

Between 1964 and 1986, 19 patients underwent resection of both a primary lung cancer and the associated brain metastasis. One patient underwent resection of 2 separate primary lung cancers and the associated metastases. The 12 men and 7 women ranged in age from 42 to 67 years (mean, 54.6 years). The cell type was adenocarcinoma in 12 tumors, squamous or adenosquamous cell in 5, large cell undifferentiated or anaplastic in 2, and malignant carcinoid in 1 tumor. The types of resection were as follows: lobectomy for 12 neoplasms, pneumonectomy for 5, bilobectomy for 2, and wedge resection for 1 neoplasm. Radiotherapy to the brain was given in connection with sixteen of the twenty craniotomies. The patient with 2 separate primary neoplasms survived 19 years before dying 5 months after the second craniotomy. The mean survival is 8.0 +/- 2.1 years (+/- the standard error), and the median survival is 1.67 years. Survival at 1 year was 65 +/- 10.7% and at 5 years, 45 +/- 11.1%. On univariate analysis, the following factors were found to correlate significantly with longer survival: a lung tumor in Stage I or II; negative mediastinal nodes; curative rather than palliative resection of the lung tumor; and age younger than 55 years. However, on multivariate analysis, only curative resection was a significant factor (p less than 0.01). We believe these results justify continued application of this combined surgical approach to patients having limited-stage lung cancer with a solitary brain metastasis.

Adenocarcinoma↗

Transcytotic pathway for blood-borne protein through the blood-brain barrier.

The transcytosis of blood-borne protein through the blood-brain barrier, a consequence of recruitment of the Golgi complex within nonfenestrated cerebral endothelia, was identified in mice and rats injected intravenously with the lectin wheat germ agglutinin (WGA) conjugated to the enzymatic tracer horseradish peroxidase (HRP). WGA enters cells by adsorptive endocytosis after binding to specific cell surface oligosaccharides. Blood-borne WGA-HRP labeled the entire cerebrovascular tree from the luminal side 5 min after injection; pericytes, located on the abluminal surface of cerebral endothelia, sequestered the lectin conjugate 6 hr later. Endothelial organelles harboring WGA-HRP 3 hr after injection included the luminal plasmalemma, endocytic vesicles, endosomes (prelysosomes), secondary lysosomes, and the Golgi complex. The peroxidase reaction product labeled the abluminal surface of cerebral endothelia and occupied the perivascular clefts by 6 hr. Within 12 hr, organelles labeled with WGA-HRP in pericytes were identical to those observed in endothelia. Blood-borne native HRP, entering cells by bulk-phase endocytosis, was neither directed to the Golgi complex nor transferred across nonfenestrated cerebral endothelia. The results suggest that blood-borne molecules taken into the cerebral endothelium by adsorptive endocytosis and conveyed to the Golgi complex can, either by themselves or as vehicles for other molecules excluded from the brain, undergo transcytosis through the blood-brain barrier without compromising the integrity of the barrier.

Animals↗

Traumatic carotid-cavernous fistula.

Carotid-cavernous fistulas are uncommon, although not rare, complications of trauma to the base of the skull; they may result in cranial nerve palsies, blindness, and occasionally in devastating subarachnoid hemorrhage. We have presented a case of carotid-cavernous fistula in a 17-year-old boy, treated successfully with balloon embolization. Although surgical treatment was advocated in the past, the low morbidity and high success rate of percutaneous balloon embolization currently make this the procedure of choice.

Adolescent↗