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Biomedical subjects

R P Levy

Publications and source records attributed to R P Levy.

At least 19 recordsLinked to original sources

Hemophilus influenza infection of an implantable insulin-pump pocket.

OBJECTIVE: To increase awareness of adverse events associated with the use of implantable insulin pumps. RESEARCH DESIGN AND METHODS: A descriptive case report of a pump implant infection. RESULTS: This is a case report of one implanted insulin pump-pocket infection among a series of 15 patients. After exposure to a child with a respiratory infection on PID 30, V.L.C. (the patient) developed a fulminant pump-pocket infection. H. influenza was recovered from it. Despite aggressive antibiotic therapy, the infection could not be controlled. Insulin delivery ceased, and the pump was explanted. The pump-pocket infection rapidly resolved with pump removal, permitting later reimplantation. CONCLUSIONS: We have adopted the American Heart Association indications and antimicrobial prophylaxis regimens recommended for prevention of endocarditis in patients with prosthetic values for patients with implanted insulin pumps.

Adult

Radiation physics for particle beam radiosurgery.

For the particles and energies considered suitable for radiosurgery, with increasing particle charge, the Bragg peak height reaches a maximum with helium and then decreases, the Bragg peak width narrows, the distal fall-off steepens, and the exit dose increases (Table 1). The helium-ion beam is superior to a proton beam because of the higher peak-plateau ratio, more rapid dose fall-off, and smaller beam deflection, and it suffers only in the modest exit dose. Comparison of the therapeutically useful parameters of these beams is complicated by the change in beam quality (LET) with depth. Considerations of RBE values, which change with the ion species and with depth of penetration, may alter the relative rankings based on one or more of these beam characterization values. For all these beams, the RBE increases with increasing LET. The effect for protons is small and occurs just at the end of range of the particles. Effective isodose distributions based on modeled beams have been reported for helium, carbon, and neon ions. These distributions include the effects of a varying RBE with changes in the beam quality (as measured by a dose-weighted LET) and the change in dose fraction size with depth (the dose per fraction is a function of the depth of penetration). These calculations suggest that the optimal charged-particle beam for radiosurgery might be carbon. Heavy charged-particle beams can produce dose distributions superior to those obtainable with photon or electron beams. In clinical trials, these dose distributions have proved to be useful for the treatment of human diseases, including neoplasia and life-threatening intracranial disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms

Charged-particle radiosurgery for intracranial vascular malformations.

Heavy charged-particle radiation has unique physical characteristics that offer several advantages over photons and protons for stereotactic radiosurgery of intracranial AVMs. These include improved dose distributions with depth in tissue, small angle of lateral scattering, and sharp distal fall-off of dose in the Bragg ionization peak. Under multi-institutionally approved clinical trials, we have used stereotactic helium-ion Bragg peak radiosurgery to treat approximately 400 patients with symptomatic, surgically inaccessible vascular malformations at the UCB-LBL 184-in synchrocyclotron and bevatron. Treatment planning for stereotactic heavy charged-particle radiosurgery for intracranial vascular disorders integrates anatomic and physical information from the stereotactic cerebral angiogram and stereotactic CT and MR imaging scans for each patient, using computerized treatment-planning calculations for optimal isodose contour distribution. The shape of an intracranial AVM is associated strongly with its treatability and potential clinical outcome. In this respect, heavy charged-particle radiosurgery has distinct advantages over other radiosurgical methods; the unique physical properties allow the shaping of individual beams to encompass the contours of large and complexly shaped AVMs, while sparing important adjacent neural structures. We have had a long-term dose-searching clinical protocol in collaboration with SUMC and UCSF and have followed up over 300 patients for more than 2 years. Initially, treatment doses ranged from 45 GyE to 35 GyE. Currently, total doses up to 25 GyE are delivered to treatment volumes ranging from 0.1 cm3 to 70 cm3. This represents a relatively homogeneous dose distribution, with the 90% isodose surface contoured to the periphery of the lesion; there is considerable protection of normal adjacent brain tissues, and most of the brain receives no radiation exposure. Dose selection depends on the volume, shape, and location of the AVM and several other factors, including the volume of normal brain that must be traversed by the plateau portion of the charged-particle beam. The first 230 patients have been evaluated clinically to the end of 1989. Using the clinical grading of Drake, about 90% of the patients had an excellent or good neurologic grade, about 5% had a poor grade, and about 5% had progression of disease and died, or died as a result of unrelated intercurrent illness. Neuroradiologic follow-up to the end of 1989 indicated the following rates of complete angiographic obliteration 3 years after treatment: 90% to 95% for AVM treatment volumes less than 4 cm3, 90% to 95% for volumes 4 to 14 cm3, and 60% to 70% for volumes greater than 14 cm3.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Image correlation of MRI and CT in treatment planning for radiosurgery of intracranial vascular malformations.

Magnetic resonance imaging (MRI) has been incorporated with stereotactic cerebral angiography and computed tomography (CT) in the treatment planning process of heavy ion radiosurgery of intracranial arteriovenous malformations (AVM's). Correlation of the images of the AVM and normal tissue on each of these neuroradiological imaging modalities is achieved by means of fiducial markers. The computerized transfer of angiographic information to the CT images regarding the size, shape, and location of the abnormal vasculature has been described in an earlier report. A separate computer program calculates a fit between individual fiducial markers on the CT and MR images that enables the transfer of contours between the two imaging modalities. The MR images aid in the determination of the 3-dimensional shape of the AVM, adding to the information derived from the two angiographic projections. Currently, MRI cannot replace cerebral angiography in delineating the entire arterial phase of the AVM. Magnetic resonance imaging is invaluable in the treatment planning of angiographically-occult AVM's, determining the location, size, and shape of the volume to be treated. Correlation of the CT and MRI images allows for the transfer of CT-calculated isodose contours to the MRI images to aid in the determination of optimal treatment plans.

Adolescent

An experimental compartmental flow model for assessing the hemodynamic response of intracranial arteriovenous malformations to stereotactic radiosurgery.

Stereotactic radiosurgery has proven to be an effective method of treating selected inaccessible or inoperable arteriovenous malformations (AVMs) of the brain. Radiation-induced obliteration of successfully-treated AVMs, however, occurs only after some latent period after treatment, depending on size, location, and dose. An experimental compartmental flow model is proposed to describe the hemodynamic alterations in the AVM as a result of the pathophysiological changes after radiosurgery, and to analyze temporal alterations in AVM blood flow rates and pressure gradients before complete obliteration. In representative small (low-flow, 150 ml/min) and large (high-flow, 440 ml/min) AVMs, it is found that increases in pressure gradients across certain vascular structures within the AVM occur during the normal course of radiation-induced flow decrease and AVM obliteration. The magnitude of these pressure alterations, however, may be within the normal physiological variations in cerebrovascular blood pressure. The effects of partial-volume irradiation of the AVM is examined by limiting radiosurgical treatment to varying portions of the flow compartments within the model. It is found that alterations in pressure gradients persist in unirradiated vascular shunts, even after complete obliteration of the treated AVM volume. These pressure alterations may increase the probability of hemorrhage from the untreated shunts of the AVM and cause redistribution of regional cerebral blood flow resulting in increased flow through these untreated shunts.

Cerebrovascular Circulation

Heavy-charged-particle radiosurgery of the pituitary gland: clinical results of 840 patients.

Since 1954, 840 patients have been treated at Lawrence Berkeley Laboratory with stereotactic charged-particle radiosurgery of the pituitary gland. The initial 30 patients were treated with proton beams; the subsequent 810 patients were treated with helium ion beams. In the great majority of the 475 patients treated for pituitary tumors, marked and sustained biochemical and clinical improvement was observed. Variable degrees of hypopituitarism developed in about one-third of patients treated solely with radiosurgery. In the earlier years of the program, 365 patients underwent radiosurgery to treat selected systemic diseases by inducing hypopituitarism. Focal temporal lobe necrosis and cranial nerve injury occurred in about 1% of patients who were treated with doses less than 230 Gy.

Acromegaly

Stereotactic helium ion Bragg peak radiosurgery for intracranial arteriovenous malformations. Detailed clinical and neuroradiologic outcome.

89 patients with angiographically documented arteriovenous malformations were treated with helium ion Bragg peak radiation. The rate of complete angiographic obliteration 2 years after radiation was 94% in those lesions smaller than 4 cm3 (2.0 cm in diameter), 75% for those 4-25 cm3 and 39% for those larger than 25 cm3 (3.7 cm in diameter); at 3 years after radiation, the corresponding obliteration rates were 100, 95 and 70%. Major clinical complications occurred in 10 patients (8 permanent, 2 transient) between 3 and 21 months after treatment; all were in the initial stage of the protocol (higher radiation doses). 10 patients bled from residual malformation between 4 and 34 months after treatment. Seizures were improved in 63% and headaches in 68% of patients. Excellent or good clinical outcome was achieved in 94% of patients. Compared to the natural history and risks of surgery for these difficult malformations, we consider these results encouraging. Heavy-charged-particle radiation is a valuable therapy for surgically inaccessible symptomatic cerebral arteriovenous malformations. The current procedure has two disadvantages: the prolonged latent period before complete obliteration and the small risk of serious neurological complications.

Adolescent

Heavy-charged-particle radiosurgery for intracranial arteriovenous malformations.

We have treated over 400 patients with symptomatic inoperable intracranial arteriovenous malformations (AVMs) with stereotactic heavy-charged-particle Bragg peak radiosurgery at the University of California at Berkeley in a collaborative program with Stanford University Medical Center and the University of California Medical Center, San Francisco. A long-term dose-searching clinical trial protocol has been developed and we have followed more than 250 patients for more than 2 years. Initially, radiation doses ranged from 45 to 35 GyE, and now doses of 25, 20, 15 and, under special circumstances, 10 GyE, depending on a number of factors, are being evaluated. The characteristics of charged-particle beams provide a relatively homogeneous dose distribution with the 90% isodose contour to the periphery of the lesion. When the entire arterial phase of the AVM core is included in the treatment field, the rates for complete obliteration 3 years after treatment are: 90-95% for volumes less than or equal to 4 cm3; 90-95% for volumes greater than 4 and less than or equal to 14 cm3; and 60-70% for volumes greater than 14 cm3. The total obliteration rate for all volumes up to 70 cm3 is approximately 80-85%. For complete radiation-induced obliteration there is a relationship of dose and volume primarily, and location secondarily. Results on relationships between dose, AVM obliteration, and complications and sequelae of the radiosurgical procedure are presented and discussed.

Adult

Stereotactic helium ion Bragg peak radiosurgery for angiographically occult intracranial vascular malformations.

Between July 1983 and July 1989, we treated 35 patients with surgically inaccessible, symptomatic angiographically occult vascular malformations (AOVMs) using stereotactic heavy-charged-particle radiosurgery. AOVMs were located in the brainstem (19), thalamus or internal capsule (9), basal ganglia (3), deep cerebral hemisphere and motor area (3), or cerebellopontine angle (1). All patients presented with clinical and radiological evidence of previous hemorrhage, usually with multiple episodes of hemorrhage. Treatment volumes ranged from 80 to 15,200 mm3 and treatment doses from 7.7 to 34.6 Gy. Mean follow-up was 40 months, with 31 patients followed for at least 2 years. Clinical outcome was excellent in 46%, good in 34% and poor in 14%; 6% died. Twenty-seven patients in excellent and good condition prior to treatment remained stable or improved neurologically. Two patients initially in poor condition, who had previously received conventional radiotherapy, died at 9 and 14 months after treatment, respectively. Six patients experienced recurrent hemorrhage 2-60 months following treatment. Three of these patients made a complete recovery. Although a larger number of treated patients must be followed over longer periods of time, stereotactic heavy-particle radiotherapy may be a valuable treatment modality for surgically inaccessible intracranial AOVMs.

Adolescent

Stereotactic heavy-charged-particle Bragg-peak radiation for intracranial arteriovenous malformations.

BACKGROUND: Heavy-charged-particle radiation has several advantages over protons and photons for the treatment of intracranial lesions; it has an improved physical distribution of the dose deep in tissue, a small angle of lateral scattering, and a sharp distal falloff of the dose. METHODS: We present detailed clinical and radiologic follow-up in 86 patients with symptomatic but surgically inaccessible cerebral arteriovenous malformations that were treated with stereotactic helium-ion Bragg-peak radiation. The doses ranged from 8.8 to 34.6 Gy delivered to volumes of tissue of 0.3 to 70 cm3. RESULTS: Two years after radiation treatment, the rate of complete obliteration of the lesions, as detected angiographically, was 94 percent for lesions smaller than 4 cm3, 75 percent for those of 4 to 25 cm3, and 39 percent for those larger than 25 cm3. After three years, the rates of obliteration were 100, 95, and 70 percent, respectively. Major neurologic complications occurred in 10 patients (12 percent), of whom 8 had permanent deficits. All these complications occurred in the initial stage of the protocol, before the maximal dose of radiation was reduced to 19.2 Gy. In addition, hemorrhage occurred in 10 patients from residual malformations between 4 and 34 months after treatment. Seizures and headaches were less severe in 63 percent of the 35 and 68 percent of the 40 patients, respectively, who had them initially. CONCLUSIONS: Given the natural history of these inaccessible lesions and the high risks of surgery, we conclude that heavy-charged-particle radiation is an effective therapy for symptomatic, surgically inaccessible intracranial arteriovenous malformations. The current procedure has two disadvantages: a prolonged latency period before complete obliteration of the vascular lesion and a small risk of serious neurologic complications.

Adolescent

Comparison of different radiation types and irradiation geometries in stereotactic radiosurgery.

Recent interest in stereotactic radiosurgery of intracranial lesions, and the development of stereotactic irradiation techniques has led to the need for a systematic and complete comparison of these methods. A method for conducting these comparisons is proposed and is applied to a set of currently-used stereotactic radiosurgical techniques. Three-dimensional treatment planning calculations are used to compare dose distributions for several different radiation types and irradiation geometries. Calculations were performed using charged particles (H, He, C, and Ne ions) and the irradiation geometry currently used at Lawrence Berkeley Laboratory. Photons in the Gamma Knife configuration and the Heidelberg Linac arc method are used. The 3-dimensional dose distributions were evaluated by means of dose-volume histograms and integral doses to the target volume and to normal brain. The effects of target volume, shape and location are studied. The charged particle dose distributions are more favorable than those of the photon methods. The differences between charged particles and photons increase with increasing target volume. The differences between different charged particle species are small, as are the effects of target shape and location.

Humans

Charged-particle radiosurgery of the brain.

Charged-particle beams (e.g., protons and helium, carbon and neon ions) manifest unique physical properties which offer advantages for neurosurgery and neuroscience research. The beams have Bragg ionization peaks at depth in tissues, and finite range and are readily collimated to any desired cross-sectional size and shape by metal apertures. Since 1954 nearly 6000 neurosurgical patients worldwide have been treated with stereotactic charged-particle radiosurgery of the brain for various localized and systemic malignant and nonmalignant disorders. Experimental studies with charged-particle beams have been carried out in laboratory animals to characterize anatomic and physiologic correlates of various behavioral and functional properties in the brain. Highly focused charged-particle beams have been used to induce sharply delineated laminar lesions or discrete focal ablation of deep-seated brain structures for the study of the functional anatomy of selected intracranial sites. Charged-particle beam irradiation for stereotactic radiosurgery and radiation oncology of intracranial disorders has achieved increasing importance internationally. More than 30 biomedical accelerator facilities on four continents are currently fully operational, under construction, or in an active planning stage; this last group consists primarily of dedicated biomedical hospital-based facilities. Therapeutic efficacy has been demonstrated clearly for the treatment of selected intracranial sites, e.g., pituitary adenomas and intracranial arteriovenous malformations. Heavier charged particles (e.g., carbon and neon ions) have been found to manifest a number of valuable radiobiologic properties and appear to be of potential advantage in the radiosurgical treatment of those primary or metastatic brain tumors that are radioresistant. The optimal dose and choice of charged-particle species must be determined for the treatment of the different intracranial disorders to improve the cure rate and to minimize potential adverse sequelae of the reaction of the brain to radiation injury.

Animals

Heavy charged-particle stereotactic radiosurgery: cerebral angiography and CT in the treatment of intracranial vascular malformations.

A method is described for stereotactic localization of intracranial arteriovenous malformations (AVM) and for calculating treatment plans for heavy charged-particle Bragg peak radiosurgery. A stereotactic frame and head immobilization system is used to correlate the images of multivessel cerebral angiography and computed tomography. The AVM is imaged by angiography, and the frame provides the stereotactic coordinates for transfer of this target to CT images for the calculation of treatment plans. The CT data are used to calculate the residual ranges and compensation for the charged-particle beam required for each treatment port. Three-dimensional coordinates for the patient positioner are calculated, and stereotactic radiosurgery is performed. Verification of the accuracy of the stereotactic positioning is obtained with computer-generated overlays of the vascular malformation, stereotactic fiducial markers, and bony landmarks on orthogonal radiographs immediately prior to treatment. Using these procedures, the accuracy of the repositioning of the patient at each of a series of imaging and treatment procedures is typically within 1 mm in each of three orthogonal planes.

Cerebral Angiography

Stereotactic heavy-charged-particle Bragg peak radiosurgery for the treatment of intracranial arteriovenous malformations in childhood and adolescence.

Forty patients aged 6 to 18 years have now been treated for inoperable intracranial arteriovenous malformations (AVMs) using stereotactic heavy-charged-particle Bragg peak radiosurgery at the Lawrence Berkeley Laboratory 184-inch Synchrocyclotron at the University of California, Berkeley. This paper describes the procedures for selection of patients, the treatment protocol, and the neurological and neuroradiological responses to stereotactic radiosurgery in this age group. The volumes of the treated AVMs ranged from 265 mm3 to 60,000 mm3. The results are favorable: thus far, 20 of 25 patients have experienced greater than or equal to 50% obliteration of their AVMs within 1 year after treatment, and 14 of 18 patients have experienced total obliteration of the AVM by 2 years after treatment. Two patients hemorrhaged from radiosurgically treated AVMs within 12 months after treatment, but none thereafter. Complications include vasogenic edema and arterial occlusion; three patients have had neurological worsening as definite or possible sequelae of treatment. The strengths and limitations of the method are discussed.

Adolescent

Intracranial vascular malformations: imaging of charged-particle radiosurgery. Part I. Results of therapy.

Twenty-four patients with intracranial vascular malformations were examined before and after helium ion radiosurgical treatment with angiography, computed tomography (CT), and magnetic resonance (MR) imaging. Twenty patients had high-flow arteriovenous malformations (AVMs). After treatment 18 of 20 AVMs (90%) showed a significant reduction in size on angiograms or MR images. Eleven of 20 (55%) had complete resolution on angiograms or MR images, 35% had partial resolution, and 10% showed no size change. Before treatment, the size range of the AVMs was 0.86-383 cm3 (median, 21.7 cm3). Smaller AVMs (less than 8 cm3) were more likely to resolve completely than medium-sized AVMs (8-64 cm3) or larger AVMs (greater than 64 cm3). Four additional patients had slow-flow vascular malformations: One had a venous angioma; one, a probable cavernous hemangioma; and two, malformations that were not seen on angiograms. CT proved inaccurate in demonstrating the boundaries of the AVM after treatment because it showed persistent contrast enhancement even when the AVM was completely obliterated on angiograms. MR imaging and angiography were complementary in the evaluation of therapeutic results and should be the primary modalities in the examination of patients with AVMs.

Adult

Intracranial vascular malformations: imaging of charged-particle radiosurgery. Part II. Complications.

Seven of 24 patients with intracranial vascular malformations who were treated with helium-ion Bragg-peak radiosurgery had complications of therapy. New symptoms and corresponding radiologic abnormalities developed 4-28 months after therapy. Five patients had similar patterns of white matter changes and mass effect on computed tomographic scans and magnetic resonance images. The abnormalities were centered in the radiation field. Gray matter changes and abnormal enhancement in the thalamus and hypothalamus outside the radiation field developed in one patient. This patient also had vasculopathic changes on angiograms. Rapidly progressive large vessel vasculopathy developed in another patient and caused occlusion of major vessels. Thus, different mechanisms may be involved in the complications of heavy-ion radiosurgery.

Adult