Use of high-frequency ultrasound imaging to improve delineation of anterior uveal melanoma for proton irradiation

The aim of this study was to evaluate high-frequency ultrasound imaging (HFUI) as an aid in localizing anterior margins of tumours of the eye for proton therapy. Proton irradiation of ocular melanoma requires an accurate assessment of all tumour margins. The tumour is marked surgically by suturing to the sclera four or five tantalum rings on the borders of the tumour defined by transillumination. In order to evaluate the clinical usefulness of high-frequency ultrasound imaging, four and five rings were surgically placed in a patient with an iris/ciliary body melanoma and in a patient with ciliochoroidal melanoma using transillumination to localize the tumour margins. Subsequently margins were verified by HFUI. In the first patient, the distances between the rings and the limbus were measured using calipers during surgery and were compared with HFUI measurements and measurements from planning software. The distances were comparable within 0.5 mm. In the second patient the treatment was planned in two different ways using EYEPLAN software. In the first scenario the shape of the tumour and its relation to the rings were obtained from the surgeon's mapping, the fundus drawing using a transilluminating point light source, and the HFUI. In the second scenario, the shape of the tumour was deduced from the ring positions only. It was observed that the maximum difference between the tumour edge as seen on high-frequency ultrasound images and the rings was 2.6 mm. The tumour volume was underestimated by 39% when tumour shape was obtained from ring positions only. During the past year we have utilized HFUI in 18 patients having tumours involving the anterior segment of the eye, among which four were treated with proton therapy. In conclusion, we believe that high-frequency ultrasound imaging provides additional information with respect to the location of tumour margins in ciliary body and anterior uveal melanoma. Occult extension of the tumour within the ciliary body or posterior iris may not be appreciated by transillumination alone.     

The effect of patient motion on dose uncertainty in charged particle irradiation for lesions encircling the brain stem or spinal cord.

A specialized charged-particle radiotherapy technique developed at Lawrence Berkeley Laboratory (LBL) is applied to patients with lesions abutting or surrounding the spinal cord or brain stem. This technique divides the target into two parts, one partially surrounding the critical structure (brain stem or spinal cord) and a second excluding the critical structure and abutting the first portion of the target. Compensators are used to conform the dose distribution to the distal surface of the target. This technique represents a novel approach in treating unresectable or residual tumors surrounding the spinal cord or brain stem. Since the placement of the patient with respect to beam-shaping devices is critical for divided-target treatments, a method for calculating dose distributions reflecting random patient motion is proposed, and the effects of random patient motion are studied for two divided-target patient examples. Dose-volume histograms and a normal-tissue complication probability model are used in this analysis. For the patients considered in this study, the normal-tissue-complication probability model predicts that random patient motion less than or equal to 0.2 cm is tolerable in terms of spinal cord complications.     

Isobutyramide, an orally bioavailable butyrate analogue, stimulates fetal globin gene expression in vitro and in vivo

Summary. Clozapine, a novel antipsychotic drug that is particularly effective in treatment-resistant schizophrenia, causes severe agranulocytosis of unknown aetiology in approximately 0·8% of U.S. patients. We evaluated potential toxic mechanisms of drug-induced agranulocytosis. Clozapine, the two major metabolites N-desmethylclozapine and N-oxide clozapine, and five other clozapine derivatives were screened for toxicity to normal haemopoietic precursors. For all compounds except N-des-methylclozapine, toxicity to CFU-GM, BFU-E and CFU-GEMM occurred at concentrations at least 10 times the normal serum levels reported in unaffected patients. In contrast, the LD₅₀ for N-desmethylclozapine was 2·5 μg/ml for CFU-GM, 3·2 μg/ml for BFU-E, and 2·4 μg/ml for CFU-GEMM, only 3–6 times the normal serum concentration. Bone marrow from patients with acute clozapine-induced agranulocytosis was not more sensitive to clozapine or N-desmethylclozapine than bone marrow from normal donors. These studies suggest that N-desmethylclozapine, the major metabolite of clozapine, is itself toxic or is further metabolized to an unstable compound which is toxic to haemopoietic precursors of both myeloid and erythroid lineages.     

Field size dependence of wedge factors

The radiation output in the presence of wedge filters is characterized by the wedge transmission factor and open beam field size factors. Conventionally, the wedge factor for high-energy photons is measured in a water phantom at depth of maximum dose for a reference field size. Experimental measurements on different wedges indicate that the wedge factors are a function of field size. An analysis of these data show that this is primarily caused by the change in scattered radiation from the treatment head in the presence of wedge filters. The change in phantom scatter and radiation backscattered to the monitor chamber are minimal. For 4- or 6-MV x rays with a 60 degrees wedge, the use of a single wedge factor measured for 10 cm X 10 cm field introduces errors of up to 3.5%, for a 16-cm-wide field. For a 20-cm-wide field with this wedge, the error is 7%. Thinner wedges exhibit less differences.     

Recovery of rat brain from a brief hyperphenylalaninemic insult early in development

Mice 14 or 60 days of age were injected intraperitoneally with [³H]leucine and were decapitated 10, 20, 40, and 80 days later. A crude fraction of brain myelin was isolated on a discontinuous sucrose gradient. Myelin was separated from the associated myelin-like material by osmotic shock and the two fractions were purified by differential centrifugation and isolated on a continuous CsCl gradient. Proteins of each subcellular fraction were separated by discontinuous gel electrophoresis in buffers containing sodium dodecyl sulfate and the specific activity of individual proteins determined. Myelin contained (in order of increasing molecular weight) two basic proteins, a protein doublet, proteolipid protein and a group of high molecular weight proteins. When animals were labeled at 14 days of age the radioactivity incorporated into the basic and proteolipid proteins of myelin was very stable metabolically (half-life much greater than 100 days), while the high molecular weight myelin proteins turned over with a half-life of about 70 days. The proteins of myelin labeled at 60 days of age turned over more rapidly, the half-life of basic and proteolipid proteins being about 95 days and that of the high molecular weight proteins about 40 days.The myelin-like material consisted primarily of high molecular weight proteins, although small amounts of basic and proteolipid protein also appeared to be intrinsic components. All the proteins of myelin-like materials turned over with a half-life of about 20 days, regardless of whether label was incorporated at 14 or 60 days of age. Thus, whereas the myelin basic and proteolipid proteins of both young and mature animals turn over very slowly as compared to the high molecular weight protein, all proteins in the myelin-like material turn over at the same, much faster rate in both young and mature animals.     

Kinematics of a selectively constrained radiolucent anterior lumbar disc: Comparisons to hybrid and circumferential fusion

Background

Despite encouraging clinical outcomes of one-level total disc replacements reported in literature, there is no compelling evidence regarding the stability following two-level disc replacement and hybrid constructs. The current study is aimed at evaluating the multidirectional kinematics of a two-level disc arthroplasty and hybrid construct with disc replacement adjacent to rigid circumferential fusion, compared to two-level fusion using a novel selectively constrained radiolucent anterior lumbar disc.

Methods

Nine osteoligamentous lumbosacral spines (L1–S1) were tested in the following sequence: 1) Intact; 2) One-level disc replacement; 3) Hybrid; 4) Two-level disc replacement; and 5) Two-level fusion. Range of motion (at both implanted and adjacent level), and center of rotation in sagittal plane were recorded and calculated.

Findings

At the level of implantation, motion was restored when one-level disc replacement was used but tended to decrease with two-level disc arthroplasty. The findings also revealed that both one-level and two-level disc replacement and hybrid constructs did not significantly change adjacent level kinematics compared to the intact condition, whereas the two-level fusion construct demonstrated a significant increase in flexibility at the adjacent level. The location of center of rotation in the sagittal plane at L4–L5 for the one-level disc replacement construct was similar to that of the intact condition.

Interpretation

The one-level disc arthroplasty tended to mimic a motion profile similar to the intact spine. However, the two-level disc replacement construct tended to reduce motion and clinical stability of a two-level disc arthroplasty requires additional investigation. Hybrid constructs may be used as a surgical alternative for treating two-level lumbar degenerative disc disease.     

An application of GafChromic MD-55 film for 67.5 MeV clinical proton beam dosimetry

The purpose of this study is to explore the use of GafChromic MD-55 (RC) film for 67.5 MeV clinical proton beam dosimetry at the Crocker Nuclear Laboratory, University of California, Davis. Several strips of RC film 6 cm x 6 cm in dimension were irradiated at a depth of 18.2 mm corresponding to the middle of a 24 mm spread-out Bragg peak (SOBP). The films were irradiated to a proton dose in the range of 0.5 Gy to 100 Gy. The beam profiles were also measured at the middle of the 24 mm SOBP. The Bragg peak was measured by using a wedge shaped phantom made of Lucite. The Bragg peak measured with RC film was compared with diode and ionization chamber measurements. After background subtraction, the calibration of the dose response of RC film showed, to a maximum deviation of 10%, a linear increase of optical density (OD) with dose from 0.5 to 100 Gy. The uniformity of OD over a single sheet of film showed a variation of +/-6%. The distal-fall off between 90% and 20% measured with GafChromic film for the Bragg peak was 1.3 mm as compared to 1.1 mm for a diode measurement and 1.4 mm for an ionization chamber measurement. The FWHM of the Bragg peak was 7.5 mm when measured with GafChromic film, 5.3 mm when measured with a diode and 8.1 mm as measured by an ionization chamber. The peak/plateau ratio with GafChromic film was 3.3 as compared to 3.7 with a diode and 3.2 with an ionization chamber. In conclusion, GafChromic MD-55 film may be a useful and convenient detector for dose measurement and quality assurance programmes of proton beams.     

Resveratrol Protects Purkinje Neurons and Restores Muscle Activity in Rat Model of Cerebellar Ataxia

Cerebellar ataxia (CA) is regarded as a miscellaneous cluster of brain disorders related to the cerebellum. Resveratrol is a naturally occurring polyphenolic compound. Previous reports suggest that resveratrol confers neuroprotection in various animal models of brain damage. Indeed, we considered it invaluable to investigate whether a treatment with resveratrol has a therapeutic role against CA induced by 3-acetylpyridine (3-AP) in rats. In addition, no investigation has examined neuroprotective effect of resveratrol in rat model of CA. Initially, 3-AP administration generated CA rat models followed by intraperitoneal injection with resveratrol. Then, motor performance and muscle electromyography (EMG) activity were assessed. Moreover, the anti-apoptotic role of resveratrol in CA and its relationship to protection of Purkinje cells were explored. According to what we have found, resveratrol administration improved the muscle activity and movement coordination in 3-AP-lesioned rats. Also under resveratrol treatment, the total number of the Purkinje neurons increased whereas a reduction in apoptotic bodies was observed. In conclusion, post-treatment with resveratrol evidently ameliorated motor performance as well as muscle activity accompanied by a protection of Purkinje cells in ataxic rats.