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M L Apuzzo

Publications and source records attributed to M L Apuzzo.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cellular and molecular neurosurgery: pathways from concept to reality--part I: target disorders and concept approaches to gene therapy of the central nervous system.

Recent advances in cellular and molecular biology and better understanding of genetic and biochemical bases of different central nervous system (CNS) disorders have made gene therapy of the CNS a realistic goal. Concept approaches for gene therapy of CNS disorders are reviewed and include the following: 1) gene replacement with a single normal allele to correct the inherited global neurodegenerative disorders, such as enzyme deficiencies; 2) brain repair to restore the function of a particular subset of cells that were lost because of a neurodegenerative process; 3) gene therapy of brain tumors; and 4) gene therapy of stroke. Techniques of viral vector-mediated CNS transfer of a therapeutic gene, transplantation of genetically modified cells, fetal embryonic implantation and/or implantation of genetically engineered neural progenitor cells, and production of a specific enzyme, neurotransmitter, and/or growth factor are discussed with respect to the therapeutic potential for global and localized CNS neurodegenerative disorders and stroke. Transfection of the CNS tumor cells with the drug susceptibility ("suicide") gene and/or "toxic" gene and antisense strategies and a concept of adoptive immunotherapy of brain tumors are also discussed. Other approaches, such as transfer of drug-resistant genes and monoclonal antibody gene transfer, are briefly discussed. In addition to summarizing current principles of gene therapy for several groups of CNS disorders, the issues that remain to be resolved in clinical reality, such as delivery of the genetic material and regulation of the cellular expression of the transgene, and the negatives associated with the concepts of gene therapy, such as transient gene expression, toxicity of viral proteins, drawbacks of antisense therapy, and the problem of immune response to the transfected protein, have been also identified.

Animals↗
PubMed1997

Cellular and molecular neurosurgery: pathways from concept to reality--part II: vector systems and delivery methodologies for gene therapy of the central nervous system.

Different vector systems that have been used and/or specifically developed for central nervous system (CNS) gene transfer studies are briefly discussed along with their advantages and disadvantages with respect to potential clinical application. These include retroviruses, recombinant herpes simplex virus, adenoviruses, adenoassociated viruses, encapsulation of plasmid deoxyribonucleic acid into cationic liposomes, and neural and oliogodendroglial stem cells. Particular attention has been paid to relate the modality of a specific CNS gene therapy to the strategy for adequate delivery of genetic material to the brain for either global or localized CNS neurodegenerative chronic disorder, as well as for CNS tumors and stroke. Techniques to circumvent the "impermeable" blood-brain barrier and how to breach the more versatile blood-brain-tumor barrier to deliver the genetic material to the target CNS cells are reviewed and include the following: 1) local stereotactic CNS injection/infusion of viral vectors, administration of vector producer cells, or cell replacement; 2) local administration of genetic material into the cerebrospinal fluid ventriculocisternal system; 3) osmotic opening of the blood-brain barrier; 4) local intra-arterial infusion; and 5) administration of blood-brain-tumor barrier permeabilizers, such as a bradykinin B2 agonist RMP-7. It is concluded that gene therapy for several brain disorders holds great potential, as suggested mainly by in vitro experiments and, to some extent, by a limited number of animal experiments. However, several drawbacks currently hamper the application of gene therapy under the clinical setting. The problems associated with gene therapy that still present major obstacles are as follows: 1) inefficient transfection of host cells by viral vectors; 2) restricted delivery of genetic material across vascular barriers of the CNS and brain tumors; 3) nonselective expression of the transgene; and 4) in situ CNS regulation of the transgene expression in a therapeutically controlled manner, as imposed by the course and phenotype of the CNS disease.

Animals↗
PubMed1997

Extracranial radiation doses in patients undergoing gamma knife radiosurgery.

OBJECTIVE: To determine extracranial doses in patients undergoing gamma knife radiosurgery and identify component sources of the extracranial doses using phantom measurements. METHODS: The lateral canthi, thyroid, sternum, and midpelvis region were monitored in 104 unselected patients during their gamma knife treatments using thermoluminescent dosimetry. Measured doses were normalized to integral dose, equivalent time (which is defined in relation to the activity of the cobalt-60 sources), and collimator size to correlate radiation doses with these parameters. A phantom was constructed from a polystyrene sphere as a model of the head adjacent to thoracic and pelvic body sections from a commercial humanoid phantom. RESULTS: On average, 18 minutes of equivalent time and five isocenters were required to achieve the prescribed dose coverage. The median prescribed dose was 18 Gy. For the lateral canthi, thyroid, sternum, and pelvis, the median doses were 24, 20, 21, and 4 cGy, respectively. Normalization to equivalent time and collimator size was superior to other techniques. Phantom measurements supported the results from patient measurements and further refined estimates of component doses to extracranial sites. CONCLUSION: Doses to extracranial sites ranged from 1.5% of the prescribed dose for the lateral canthi to 0.2% for the pelvis. Doses to the sternum and pelvis were proportional to the duration of irradiation. Scatter radiation contributed more than 50% of the dose to the canthi and thyroid. Leakage radiation typically contributed 80 to 90% of the dose to the sternum and pelvis. Radiation during patient couch transit contributed little to the doses at the measured extracranial sites.

Adult↗
PubMed1996

The Richard C. Schneider Lecture. New dimensions of neurosurgery in the realm of high technology: possibilities, practicalities, realities.

Fueled by a buoyant economy, popular attitudes and demands, and parallel progress in transferable technical and biological areas, neurosurgery has enjoyed a remarkable quarter of a century of progress. Developmental trends in the discipline have included the following: 1) a refinement of preoperative definition of the structural substrate, 2) miniaturization of operative corridors, 3) reduction of operative trauma, 4) increased effectiveness at the target site, and 5) incorporation of improved technical adjuvants and physical operative tools into treatment protocols. In particular, the computer has become a formidable ally in diagnostic and surgical events. Trends in technical development indicate that we are entering an exciting era of advanced surgery of the human cerebrum, which is heralded by the following: 1) current developments in areas of imaging, sensors, and visualization; 2) new devices for localization and navigation; 3) new capabilities for action at the target point; and 4) innovative concepts related to advanced operative venues. Imaging has provided structurally based surgical maps, which now are being given the new dimension of function in complex and integrated formats for preoperative planning and intraoperative tactical direction. Cerebral localization and navigation based on these advances promise to provide further refinement to the field of stereotactic neurosurgery, as linked systems are superseded by more flexible nonlinked methodologies in functionally defined volume-oriented navigational databases. Target point action now includes not only ablative capabilities through micro-operative methods and the use of stereotactically directed high-energy forms but also the emergence of restorative capabilities through applications of principles of genetic engineering in the areas of molecular and cellular neurosurgery. Complex, dedicated, and self-contained operative venues will be required to optimize the emergence and development of these computer-oriented micro/stereotactic capabilities, which appear to be unavoidably required as locales for the practice and development of virtual reality-based stations for operative rehearsal, simulation, training, and, ultimately, enhancement of operative events through robotic interfaces. Primary impetus for progress has relied upon new combinations of technologies, disciplines, and industries. Philosophical and practical problems include the spectrum of availability of these methods to the population at large, the training of individuals to properly administer these methods, defining the acceptable envelope of expertise, and maintaining suitable delivery and progress while containing spiraling costs. Advanced neurological surgery and the use and development of high-technology adjuvants require a robust economy that has a populace willing to invest in the luxury of such developments. The current socioeconomic situation is fragile from the standpoint of both economics and attitudes of the patients and health care providers, with diversion of economic resources, redistribution of funding bases, modification of patient referrals, practice styles, and service attitudes undermining progress. Economic pressures have brought high-technology methods under great scrutiny regarding their effectiveness and cost-effectiveness. Reform proposals have specifically targeted technology-oriented services, and the Office of Technology Assessment has recommended increasing the use of managed care providers who look to information on cost-effectiveness and clinical practice guidelines to establish efficient management strategies and issue "report cards." Although the premise is laudable and "gimmickry" needs to be identified, it might be argued that such scrutiny and control might be overbearing and overused, impeding appropriate delivery and progress.

Cost-Benefit Analysis↗
PubMed1996

Vagus nerve stimulation activates central nervous system structures in epileptic patients during PET H2(15)O blood flow imaging.

OBJECTIVE: To determine the central areas of activation by vagal nerve stimulation (VNS) in epilepsy. VNS is a promising neurosurgical method for treating patients with partial and secondary generalized epilepsy. The anti-epileptic mechanism of action from VNS is not well understood. METHODS: We performed H2(15)O PET blood flow functional imaging on three patients with epilepsy in a vagal nerve stimulation study (E04 Protocol with Cyberonics). The three patients included two that had previous epilepsy surgery but continued to have frequent seizures. Seizure onset was frontal in two patients and bitemporal in the third patient. Twelve PET scans per subject were acquired every 10 minutes with a Siemens 953/A scanner. In 6 stimulus scans, VNS was activated for 60 seconds (2 mA, 30 Hz) commensurate with isotope injection. In 6 control scans no VNS was administered. No clinical seizures were present during any scan. Three way ANOVA with linear contrasts subject, task, repetition) of coregistered images identified significant treatment effects. RESULTS: The difference between PET with VNS and without revealed that left VNS activated right thalamus (P < 0.0006), right posterior temporal cortex (P < 0.0003), left putamen (P < 0.0002), and left inferior cerebellum (P < 0.0009). CONCLUSIONS: VNS causes activation of several central areas including contralateral thalamus. Localization to the thalamus suggests a possible mechanism to explain the therapeutic benefit, consistent with the role of the thalamus as a generator and modulator of cerebral activity.

Adult↗
PubMed1996

Mechanical malfunction of the Leksell Gamma knife during patient treatment.

During the course of a patient treatment with a North American U-type gamma unit, the remote hydraulic valve controlling the direction of couch motion failed to change state. The couch, helmet and patient remained in treatment position after the expiration of treatment time for one of the target shots. No unusual equipment warning indications had been observed prior to the malfunction. The gamma unit was new, having been used to treat approximately 20 patients since it had begun to be used clinically 11 weeks previously. This specific situation was not addressed in our posted Emergency Procedures, which dealt explicitly with loss of electrical power, and loss of hydraulic pressure. In the present case, the hydraulic gauges indicated full pressure. After attempts to disengage the patient remotely proved unsuccessful, personnel entered the room. The table clutch at the foot of the couch was operated to disengage the couch/helmet assembly from its docked position. While this was not mentioned in our emergency procedures, the act had the effect of causing the cobalt-60 sources to be misaligned with the collimator apertures, thereby immediately terminating the patient treatment. This also had the unanticipated effect of substantially reducing radiation leakage exposure rate next to the couch near the tunnel opening. The patient was released from the helmet trunnions using a manufacturer-supplied long-handled special Allen key. The key was used conventionally, to release the trunnion locking mechanism, and also unconventionally to force a separation of a trunnion from the docking slot on the patient head frame. The patient was then removed from the tunnel by sliding out the pad on which she was lying. Anesthesiology personnel accompanied the patient out of the room. The unit functioned properly upon the replacement of the valve by manufacturer service personnel the next day. The patient returned for completion of treatment 1 week later. There were only minor changes to the overall patient dosimetry as a result of the malfunction. Personnel exposures were very low. The malfunction was reported to State authorities, who conducted an investigation, that was in turn followed up by an investigation by the Nuclear Regulatory Commission.

Dose-Response Relationship, Radiation↗
PubMed1996

Gamma unit facility: concept genesis, architectural design and practical realization.

The physical creation of a gamma unit facility requires the development of a broad-perspective multidisciplinary plan. The primary goal is radiosurgical treatment of intracranial lesions in a functional environment. The practical realization of a facility optimally designed for patient treatment is dependent on factors which include the facility setting, architectural goals, radiation safety requirements, and patient and medical team needs. This necessitates combined intellectual resources from neurosurgery, radiation oncology and physics, anesthesia, radiology, nursing, administration, and architectural and engineering teams. We undertook the development of a gamma unit facility which optimized the ergonomics and efficiency of patient evaluation, care and treatment, given the instrument requirements. This general plan based on our experience can be used for the development of other gamma unit facilities.

Clinical Protocols↗
PubMed1996

Treatment of recurrent malignant gliomas with chronic oral high-dose tamoxifen.

The present clinical trial was undertaken to assess the clinical safety and possible efficacy of administering tamoxifen to patients with recurrent malignant glial tumors at dosages calculated to achieve levels sufficient to inhibit protein kinase C within the tumor cells. Chronic p.o. tamoxifen was administered in very high dosages to 32 patients (20 males and 12 females; age range, 26-75 years; mean, 49 years) with histologically verified malignant glioma [anaplastic astrocytoma (12 patients) or glioblastoma multiforme (20 patients)] who had demonstrated clinical and radiographical progression or recurrence following external beam radiation therapy (and additional chemotherapy in 11; immunotherapy in 2). The dosage of tamoxifen administered was 200 mg/day to males and 160 mg/day to females given in a twice daily schedule. Clinical and radiographical (defined as a greater than 50% decrease in volume of the enhancing lesion volume on magnetic resonance imaging and a decrease in metabolic activity on serial positron emission tomographic scans) response was noted in 8 patients (25%; 4/12 with anaplastic astrocytoma and 4/20 glioblastoma multiforme), with an additional 6 patients (19%) exhibiting stabilization of disease with minimal side effects. Median survival from the time of diagnosis for the entire cohort was 24 months (104 weeks), for the anaplastic astrocytoma group 42.5 months (185 weeks), and for the glioblastoma group 17.4 months (75.5 weeks). From the initiation of tamoxifen, median survival for the entire cohort was 10.1 months (44 weeks), for the anaplastic astrocytoma group 16 months (69 weeks), and for the glioblastoma group 7.2 months (31 weeks). The mean length of follow-up of all patients after initiating tamoxifen was 16 months (69 weeks), while the mean length of follow-up of alive patients is 22.6 months (98 weeks) (range up to 51 months). These data suggest that a subgroup of patients with malignant gliomas respond or stabilize with chronic high-dose tamoxifen therapy. This therapy may represent an alternative or adjuvant to existing chemotherapies for these tumors; further clinical trials are warranted.

Administration, Oral↗
PubMed1995

Magnetic resonance imaging of cystic meningiomas and its surgical implications.

Our purpose was to document the incidence and imaging features of cystic meningiomas, to correlate the imaging features of cystic meningiomas with the histopathological findings, and to analyze the surgical implications of the imaging features of cystic meningiomas. The imaging studies, clinical histories, operative findings, and histopathological findings of a total of 128 patients with meningiomas were reviewed retrospectively. The 15 cystic meningiomas in our series could be morphologically divided into three major types: cystic areas contained wholly within the tumor (6 meningiomas), cystic areas at the periphery of, but wholly within, the margins of the tumor (5 meningiomas), and cystic areas peripheral to the tumor, lying on the adjacent brain (4 meningiomas). A majority of cystic meningiomas were histopathologically diagnosed to be meningothelial (8 of 15 meningiomas). Cellular atypia was seen in many patients. Meningiomas may simulate astrocytomas or metastatic lesions on imaging studies. Magnetic resonance imaging had a diagnostic accuracy of 80% (12 of 15 patients), which was significantly better than the computed tomography diagnostic accuracy of 50% or less. Magnetic resonance imaging with contrast enhancement could distinguish Type 2 (cyst wall containing tumor cells) and Type 3 (cyst wall containing gliotic tissue without tumor invasion) cystic meningiomas. Cyst wall enhancement was seen in Type 2, but not in Type 3, cystic meningiomas. Cystic meningiomas represented approximately 10% of all meningiomas in our series. Histiologically, they were usually relatively aggressive, which probably partly explains why cystic changes may be secondary to tumor necrosis or hemorrhage. Recognition of the diagnostic features of cystic meningiomas is important, because they may mimic metastatic neoplasms or primary gliomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Ventroposterior medial pallidotomy in patients with advanced Parkinson's disease.

In a preliminary study, the effects of ventroposterior medial pallidotomy were evaluated in five patients with advanced Parkinson's disease in whom medical therapy had failed. The mean age was 67.0 +/- 5.6 years, and the mean Hoehn and Yahr stage when "off" was 3.9 +/- 1.3. Three patients received unilateral pallidotomies; two of these received another pallidotomy after 8 weeks. Two other patients received staged bilateral pallidotomies. No significant differences in overall function could be seen before and after the first surgical procedure. All three patients with peak-dose dyskinesias or dystonia had marked contralateral reduction in these symptoms. Ventroposterior medial pallidotomy can ameliorate peak-dose dyskinesias in patients with advanced Parkinson's disease. Overall function improvement is not remarkable.

Aged↗
PubMed1995

Third ventricular cysticercal cyst mimicking a colloid cyst: case report.

We describe a case of a 28-year-old Latino man who presented with signs and symptoms of raised intracranial pressure and radiographic evidence of a third ventricular cystic lesion. The cyst was removed via a transcallosal approach; the histology was noted to be a cysticercal lesion. The radiographic and histological features of this interesting case are discussed.

Adult↗
PubMed1995

Gunshot wounds to the head in an urban setting.

The literature reveals several ominous trends in firearm injuries in the United States. The crack epidemic of the mid-1980s, the increasing availability of handguns and more lethal weapons, and, particularly in Southern California, the rise of gang violence have all contributed significantly to this trend. Although the crack epidemic seems to have abated, the weapons it produced and the criminal elements it encouraged are still around. Many public health experts have advocated gun control as a means to stop this violence, and they have several compelling examples to justify their efforts. Gun control, however, is beyond the scope of this article. Neurosurgeons can have some effect at the local level on gang violence, however. The University of Southern California Department of Neurological Surgery has been working with the Think First Organization and Community Youth Gang Service Organization to reach out to children before they become involved with the gangs. These organizations are also working with the justice system to reform young people already involved with gangs. The hope is that these patterns of violence can be arrested on the community level.

Craniocerebral Trauma↗
PubMed1995

Patients with Glasgow Coma Scale scores 3, 4, 5 after gunshot wounds to the brain.

Even this information is only partial. To study fully the effects of treatment would require optimal care at all points from time of injury, including rapid prehospital resuscitation, rapid transport to an optimally equipped and staffed hospital, immediate evaluation and treatment of the initial injury and all complications, rapid and comprehensive rehabilitation, and supportive and flexible home and work settings for the patient on discharge. Patients would need to be stratified for premorbid characteristics, including intelligence, personal traits, and training. Prolonged follow-up, possibly for several years, would be required to determine true outcome. No current study contains sufficient numbers of patients treated optimally and studied for prolonged periods, but this should be done. One way of looking at such patients is to decide that many should be treated to salvage a few. The other way of looking at them is that so many must receive care, at great emotional and economic cost to themselves and others, that such treatment is inappropriate for any of them. Treating all such patients would be a major undertaking. If most of these patients were treated vigorously, a great proportion of them would still die but probably not for a number of days. During this period, their families would be under extreme stress. Once stabilized and receiving ongoing care, some patients would enter a permanent vegetative state and survive for prolonged periods until their prognosis was clear and care was withdrawn, again causing family stress as well as high cost. Some would likely survive although impaired. The charges and real costs of care for all these patients would be tremendous. The question therefore arises as to how to decide what to do about caring for a large group of patients whose maximal care would be costly in emotional and financial terms, particularly at a time when it is recognized that resources for medical care are going to be limited. When discussing such patients as a group with a view toward developing practice guidelines, many considerations must be brought to bear. One consideration is the certainty of the prognosis in both a quantitative and a qualitative sense in an individual case. It is not clear that one can be certain in patients except when there are overwhelmingly unfavorable features. As has been noted, even patients who have been shot through the geographic center of the brain and are posturing can make excellent recoveries. This would push toward aggressive treatment for many patients. Decision making must therefore be considered in terms of bioethics. The major principle-based systems of bioethics are deontologic, arising from accepted principles, and utilitarian, arising from effect on outcome. A virtue-based ethic for physicians arising from "the caring bond and the public trust" is being revived as a balance to analytical ethics. A similar orientation from the point of view of patients is communitarian ethics, that is asking for only what is reasonable and not so much as might harm others. Some of the issues to be considered include the sanctity of life while taking into account the criteria for life--vegetative function versus some level of mental function. One must also review each decision from the viewpoints of all the parties involved--patients, family and friends, physicians, and society--in the context of a heterogeneous society in which individual rights and tolerance enforced by law are primary features. In the patients' terms, there is a desire and right to medical care to maintain a healthy productive life. Even if impaired to some extent, patients may still have an interest in living. Balancing benefits and burdens of life is a complex problem. There is also the right, based on patients' values, to refuse care if there is the wish not to take a chance of having a significantly compromised existence. Such declaration before injury should be honored...

Brain Injuries↗
PubMed1994

The use of lobectomy in the management of severe closed-head trauma.

A retrospective review is presented of 20 patients with traumatic brain injury who were treated during the course of their illness by lobectomies either after a herniation or other significant deterioration or to reduce elevated intracranial pressure. All the patients suffered from blunt head trauma. Patient ages ranged from 19 to 59 years (average, 34 yr). The initial Glasgow Coma Scale score ranged from 3 to 15 (average, 8.2). There were 14 frontal lobectomies, 2 temporal, 3 frontal and temporal, and 1 occipital. Surgery was performed between 0 and 8 days after injury (average, 2.8). Outcome was favorable (good or moderately disabled) in 11 patients and unfavorable (severely disabled, persistently vegetative, or dead) in 9. No patients survived in a persistently vegetative state. A higher initial Glasgow Coma Scale score was positively correlated with a more favorable outcome (P < 0.03). Younger patients also showed a significant positive relationship to outcome (P < 0.0005). Better pupillary reactivity showed a significant trend toward a more favorable outcome (P < 0.04). The type of lesions identified on computed tomographic scans had no association with outcome. A lobectomy can be a useful adjuvant in the management of severe brain injury, especially in younger patients with relatively higher initial Glasgow Coma Scale scores who subsequently deteriorate or develop elevated intracranial pressure.

Adult↗
PubMed1994

Outcome prediction after penetrating craniocerebral injury in a civilian population: aggressive surgical management in patients with admission Glasgow Coma Scale scores of 3, 4, or 5.

In an attempt to evaluate the response of patients who have low admission Glasgow Coma Scale scores (GCS) after a penetrating craniocerebral injury to aggressive management, we evaluated a series of 190 patients with penetrating injuries who presented with a GCS score of 3, 4, or 5 during a 6-year period. Entrance criteria required replicable neurological examinations that were not altered by the presence of hypotension, drugs/toxins, or systemic injury. The surgical patients included 21 patients with an admission GCS score of 3, 24 with an admission GCS score of 4, and 15 with an admission GCS score of 5. All patients underwent surgical intervention and aggressive perioperative management in the neurosurgical intensive care, including resuscitative protocols. Five of the patients with a GCS score of 3 survived, all with poor outcomes. Seven of the patients with a GCS score of 4 survived, although only one had a good outcome. Eleven of the patients with a GCS score of 5 survived. Five had a Glasgow Outcome Score of 2, five had a Glasgow Outcome Score of 3, and one had a Glasgow Outcome Score of 4. We have devised a prospective model of outcome based on our series in an attempt to predict nonsurvivors at admission (while overpredicting for survivors). The variables most predictive of mortality include admission GCS score and subarachnoid hemorrhage in one model and admission GCS score and pupillary changes in a second, when pupillary response was definitive at admission (P < or = 0.00005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗