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Biomedical subjects

M Salcman

Publications and source records attributed to M Salcman.

At least 73 records · Page 4Linked to original sources

Arteriovenous malformations of the superior cerebellar artery: excision via an occipital transtentorial approach.

Arteriovenous malformations (AVMs) of the superior cerebellar artery (SCA) are unusual and difficult lesions to treat, representing less than half of all AVMs located in the posterior fossa. Traditional approaches for surgical extirpation include the subtemporal transtentorial and suboccipital supracerebellar routes. On the basis of our recent experience with three SCA-supplied AVMs, we advocate an occipital transtentorial approach similar to that used for neoplasms of the pineal gland. Exposure of the AVM from above and in the midline provides superior visualization of the deep veins, the SCA arborization in the retrocollicular space, and the rostral cerebellum, without exposing the temporal lobe and the 4th nerve to surgical trauma in a narrow, confined space. Superior cerebellar AVMs that arise from the caudal branch of the SCA on the superolateral aspect of the hemisphere are more easily handled by standard suboccipital methods.

Adult↗

Wide variation in risk of wound infection following clean neurosurgery. Implications for perioperative antibiotic prophylaxis.

The authors have prospectively examined the occurrence of postoperative wound infection following clean neurosurgery in 936 patients. Fewer than 1% received perioperative antibiotic prophylaxis. The overall rate of deep wound infection was 2.6%; no deaths were directly attributable to these infections. Deep wound infections occurred significantly more frequently following craniotomy (4.3%) than following spinal (0.9%) or other clean neurosurgery. Among craniotomies, the deep wound infection rate varied significantly from 11% following repeat operations for recurrent gliomas to 2.5% following non-tumor surgery. Risk of deep wound infection varied more than 11-fold depending on the type of clean neurosurgical operation. It is most feasible to demonstrate the potential efficacy of perioperative antibiotics in clean neurosurgical procedures with the greatest risk of postoperative wound infection. The potential benefit from such prophylaxis would be greatest for patients undergoing these high-risk operations.

Adult↗

The morbidity and mortality of brain tumors. A perspective on recent advances in therapy.

This article reviews current morbidity and mortality statistics for the major classes of primary brain tumors including malignant astrocytoma, glioblastoma, low-grade astrocytoma, oligodendroglioma, meningioma, and other benign tumors and metastatic tumors. Innovations in therapy are discussed for surgery, radiation, chemotherapy, and such newer areas as hyperthermia, immunotherapy, and phototherapy.

Adjuvants, Immunologic↗

Resection and reoperation in neuro-oncology. Rationale and approach.

The author presents a discussion of the role of radical resection and reoperation in the treatment of patients with malignant brain tumors. Mechanical cytoreduction, morbidity and mortality associated with surgery, reoperation, principles of the surgical method, and the future of surgery are detailed.

Astrocytoma↗

Removable high intensity iridium-192 brain implants. Technique and in vivo measurements in canine brain.

A preclinical evaluation of the technical details and dosimetry for temporary high intensity 192Ir brain implants is presented. The canine brain was used for this quality assurance study in which direct in vivo dose measurements were done by thermoluminescent dosimetry (TLD rods). Precise and reproducible positioning of the TLD rods and 192Ir ribbons were assured by simple accessories which can be utilized in the clinical situation. The neurosurgical procedure for this non-routine interstitial implant of the brain, suitability of type and size of afterloading cannulas and facility for firmly anchoring them to the scalp, and comparison of measured doses with computer-predicted values are details assured by the canine study. Agreement between the in vivo determination and computer-generated doses was consistently in the range 2-5%. Data derived from this preclinical evaluation are currently used in both stereotactic and non-stereotactic brain implants at our institution. Details are presented for the implant procedure, dose measurements and brachytherapy planning for multiple ribbons. The latter incorporates direct interaction on computed tomography (CT) images for a hypothetical patient case.

Animals↗

A multiple floating microelectrode for chronic implantation and longterm single unit recording in the cat.

This paper describes a multiple electrode, suitable for chronic implantation and single unit recording in the superficial cerebral cortex of the cat. The electrodes are fine wires, 5-8 per implant, not kept together in a bundle; a segment of them floats freely in saline in a closed chamber over the place of penetration. The electrode tips are not sharpened electrolytically, but cut at a bevel during surgery. Longevity of the implants is improved by slowing down the occasional rapid head shaking characteristic of cats, which tends to tear out implanted electrodes, by means of a small weight attached by a bar to the head.

Animals↗

Occurrence of glioblastoma multiforme in three generations of a cancer family.

We report a cancer family in which glioblastoma multiforme occurred in each of three successive generations and strictly in the paternal lineage. The pedigree is consistent with an autosomal-dominant pattern of inheritance, and this conclusion is supported by the incidence of other tumors within the family. Ten of the 23 blood relations of the proband have developed cancers (43.5%), and 5 of these have been breast carcinomas. The clinical importance of the cancer family syndrome is discussed, as is the relevance of genetic factors in the expression of the neoplastic phenotype.

Adult↗

Intramedullary subependymoma of the cervical spinal cord: case report.

The third case of intramedullary subependymoma of the cervical spinal cord is reported. This is the first such case for which intraoperative views are available. It was possible to remove most of this lesion with the aid of the operating microscope, the carbon dioxide laser, and the use of somatosensory evoked potentials. The diagnosis was clouded by the coexistence of Holmes-Adie pupils and absent reflexes in the lower extremities. All three reported intramedullary subependymomas have been found in the cervical spinal cord of middle-aged patients. Tumors in this clinical setting should not be assumed to be unresectable astrocytomas without careful histopathological and intraoperative evaluation.

Adult↗

Estrogen and progesterone receptors in meningiomas.

Two-thirds of all meningiomas and four-fifths of intraspinal and sphenoidal meningiomas occur in women. Meningiomas frequently enlarge or become symptomatic during pregnancy or during the luteal phase of the menstrual cycle. There is an increased incidence of meningiomas in women with breast carcinoma. In a series of 23 patients with meningiomas, the authors assayed biopsy specimens of the tumor for the presence of estrogen (ER) and progesterone (PR) receptors, using glycerol density gradient centrifugation and dextran-coated charcoal techniques. Significant levels of ER were found in only 17% of the patients, while significant PR levels were detected in 39%. Only one of the 16 tumors from female patients had significant ER levels, whereas three of the seven tumors from men had significant ER levels. Eight of the 16 tumors in women had significant PR levels, whereas only one of the seven tumors in men had a significant PR level. Thus, three out of four tumors with definite ER were from men, whereas eight of nine tumors with definite PR were from women. Of the eight women whose tumors contained PR, three were premenopausal and five postmenopausal. The single tumor with high levels of PR in the male patient was histologically atypical. The results of this series were compared with six published series of sex steroid assays in meningiomas. These seven series were divided into two groups: one group included two reports from the same laboratories in France, and the other the remaining five reports. Much higher percentages of both ER- and PR-positive tumors were reported from the French group. The authors suggest that this discrepancy may be due to the use of preoperative glucocorticoid therapy in the series from the United States. Since meningiomas are known to enlarge during periods when levels of circulating progestins are high, the presence of significant quantities of PR in a high percentage of tumors may have therapeutic implications for recurrent, malignant, or incompletely excised tumors, or for medically fragile patients. Conversely, since meningiomas are not known to enlarge during the proliferative phase of the menstrual cycle or with exogenous estrogen therapy, the small number of tumors positive for ER may indicate that ER lacks clinical significance. High levels of PR found in a small group of histologically aggressive tumors in several series may indicate that hormonal therapy may be especially useful in this difficult subset of patients.

Adult↗

The pharmacology of diaziquone given in intravenous or intracarotid infusion to normal and intracranial tumor-bearing puppies.

Diaziquone (also called "aziridinyl benzoquinone," or AZQ), an antitumor drug designed to penetrate the blood-brain barrier, has demonstrated activity against central nervous system (CNS) neoplasms. Four-hour infusions of carbon-14 (14C)-labeled AZQ (0.8 mg/kg) were given via the left common carotid artery or left brachial vein to two groups of puppies. A third group, harboring a transplantable canine glioma, received 14C-AZQ by intravenous infusion. Levels of chloroform (CHCl3)-extractable 14C (AZQ only) and total 14C (AZQ and metabolites) were determined in serial samples of plasma and cerebrospinal fluid (CSF). At the end of the infusion time, total and CHCl3-extractable 14C levels were determined in brain and tumor. Intra-arterial infusion of AZQ caused no histological abnormalities in the retina or brain. For the intravenous infusion group, the concentrations of CHCl3-extractable 14C (in nmol/ml or nmol/gm) were 0.68, 0.35, and 0.84 for plasma, brain, and CSF, respectively. For the intra-arterial infusion group, the concentrations were 0.25, 0.13, and 0.32 for plasma, brain, and CSF, respectively. Comparison of right and left hemispheres following intra-arterial infusion showed a slightly higher concentration of 14C in the ipsilateral (left) hemisphere, with concentrations (nmol/gm) of CHCl3-extractable 14C/total of 14C of 0.15/0.87 on the left and 0.12/0.65 on the right. Concentrations (nmol/gm) of CHCl3-extractable 14C/total 14C in brain and tumor were 0.60/1.24 and 0.58/1.65, respectively. In tumor-bearing animals, tumor and surrounding brain contained similar concentrations of AZQ, but there were higher concentrations of metabolites in tumor. This may reflect different metabolism of AZQ within brain and tumor or different permeability to metabolites. This study revealed that AZQ enters the CNS and brain-tumor tissue in substantial concentrations and that there is no significant advantage to intracarotid infusion of AZQ.

Animals↗

Intramedullary canine spinal cord tumor model.

The development of a transplantable model brain tumor in the neonatal dog, the adaptation of the tumor to tissue culture, and the successful growth of the tumor in adult mongrel dogs has been adapted to producing similar tumors in the thoracic spinal cord of the adult dog. Ten adult dogs, weighing 4 to 25.4 kg each, were subjected to formal laminectomy. The tumor cell suspension was injected by hand with a Hamilton syringe at two or three sites over a distance of 1 cm; each site received an injection volume to 0.02 to 0.05 cc of the cell suspension after the dura had been opened. Immediately after injection the field was copiously irrigated and the puncture area sealed with a single drop of ethyl cyanoacrylate. Tumor cells for injection were obtained by thawing ampules stored at -195 degrees C in a mixture of 10% dimethyl sulfoxide and RPMI 1640 culture medium. Cells were resuspended in Hank's balanced salt solution and 15% fetal calf serum on ice. Solutions had 90% cell viability, and animals received a dose in the range of 3 to 13 X 10(6) cells. Eight animals developed tumors and became paraparetic on the 9th to 14th postinjection day. Metrizamide myelography in three animals revealed complete blocks; two animals underwent spinal computerized tomography (CT) and demonstrated syringohydromyelia. Histology revealed the tumors to be highly vascular primitive neoplasms that invaded the surrounding cord. This spinal cord tumor model is large enough to be operated on, studied by CT and myelography, and subjected to pharmacological, electrophysiological, and blood flow study.

Animals↗

The plasma pharmacokinetics and tissue distribution of dimethyl sulfoxide in mice.

We defined the plasma and tissue concentrations and pharmacokinetics of dimethyl sulfoxide (DMSO) in 22-34 g male Swiss Webster mice injected i.v. with 15% DMSO at a dosage of 1.5 mg per g. Concentrations of DMSO in alkalinized, perchloric acid extracts of tissue and plasma were determined by gas-liquid chromatography. Plasma concentrations of DMSO declined in a biexponential fashion that was well described by the equation Ct = 2.36 exp(-0.449 t) + 1.28 exp(-0.00768 t), indicating a t 1/2 (alpha) of 1.5 min and t 1/2 (beta) of 90 min. DMSO was rapidly and extensively distributed through tissues and was not concentrated in any particular tissue, although at 1 min after injection, the brain contained the lowest concentration of DMSO of any tissue studied. By 8 hr after injection, there was little DMSO in plasma or any tissue. Intravenous injection of DMSO produced neuro-muscular disturbances, hemolysis, and hemoglobinuria in all animals. Intravenous injection of DMSO produced little increase in plasma osmolality and did not produce any histological evidence of central nervous system or renal tubular damage.

Animals↗

Interstitial microwave hyperthermia for brain tumors. Results of a phase-1 clinical trial.

The technical feasibility and clinical safety of interstitial microwave hyperthermia was evaluated in six patients with glioblastoma and malignant astrocytoma. Prior to entry into the study, each patient had received surgery, radiation and nitrosourea chemotherapy. All patients were implanted at open craniotomy with a flexible microwave radiator/sensor (o.d. 1.5 mm) and transcutaneously connected to a 245- MHz microwave generator. Intraoperative thermal field plots and cooling curves were obtained with the aid of non-perturbing probes (o.d. 1.2 mm) perpendicularly driven into the tumor at fixed radial distances from the central antenna. In comparison to similar measurements carried out in normal feline brains, human gliomas were unable to efficiently dissipate heat as demonstrated by doubling of the effective diameter of the thermal field to 4 cm and by prolongation of the decay time in all cooling curves. Patients were also implanted with subarachnoid ICP monitors over the contralateral hemisphere. Two postoperative treatments were given at 45 degrees C for 60 min on the night of surgery and 48 hr later. No patient was aware of power on/power off, there were no permanent neurologic sequelae and there were no significant changes in the ICP. Power was manually controlled with visual feedback in the first three patients and automatically controlled by a computer-based system in the final three patients. Four of the six patients have lived 18 months after implantation and two of these have negative CT scans at 18 and 27 months since recurrence. It appears that interstitial microwave hyperthermia is both feasible and safe within the intracranial cavity and that combined interstitial irradiation and hyperthermia deserves clinical study.

Adult↗

Primitive neuroectodermal tumor in a 57-year-old man.

Primitive neuroectodermal tumors are rare cerebral neoplasms previously described only in children and young adults. This report describes such a tumor arising in the left frontal lobe of a 57-year-old man. After surgical resection and radiation therapy to the primary site, the patient developed extensive central nervous system metastases that led to his death. The histopathologic, radiographic, and clinical features of this case suggest that future therapeutic protocols for primitive neuroectodermal tumor should be similar to those for childhood medulloblastoma or neuroblastoma.

Age Factors↗

Brain-blood barrier? Yes and no.

Ventriculo-cisternal perfusion of horseradish peroxidase (HRP) in the mouse brain has demonstrated that a brain-blood barrier exists at the microvascular endothelium in brain parenchyma but not in the median eminence of the hypothalamus. The brain-blood barrier is similar to the blood-brain barrier in that: tight junctions prevent the movement of protein between endothelial cells, HRP taken into the endothelial cells is directed to lysosomal dense bodies, and, contrary to the literature, a vesicular transendothelial transport of HRP from brain to blood does not occur under normal conditions. The endocytosis of ventricular injected HRP from the abluminal side of the endothelium is demonstrably less than the endocytosis of intravenous injected HRP from the luminal side; hence, the cerebral endothelium expresses a degree of polarity regarding the internalization of its cell surface membrane and extracellular protein. The passage of cerebrospinal fluid-borne or blood-borne HRP between some ependymal cells of the median eminence is not precluded by tight junctions. These patent extracellular channels offer a direct pathway for the exchange of substances between cerebrospinal fluid in the third ventricle and fenestrated capillaries in the median eminence.

Animals↗

Cytochemical localization of glucose-6-phosphatase activity in cerebral endothelial cells.

Glucose-6-phosphatase (G6Pase) activity, with glucose-6-phosphate and mannose-6-phosphate as substrates, was examined by cytochemistry in capillary and arteriole endothelial cells of the mouse brain. G6Pase activity was observed ultrastructurally in the lumen of the nuclear envelope and endoplasmic reticulum (ER) of these cells. The reactive ER and nuclear membrane appeared to be in continuity. Nucleoside diphosphatase activity, also a marker for the ER in some cell types, was not seen within the ER of the cerebral microvasculature. The ER of arterioles and capillaries did not bind lead nonspecifically when incubated in a substrate-free medium. Speculation is raised concerning the involvement of G6Pase in glucose metabolism of cerebral endothelial cells and in making blood-borne glucose available to brain parenchyma.

Animals↗