Optimization and clinical use of multisegment intensity-modulated radiation therapy for high-dose conformal therapy.

Intensity-modulated radiation therapy (IMRT) may be performed with many different treatment delivery techniques. This article summarizes the clinical use and optimization of multisegment IMRT plans that have been used to treat more than 350 patients with IMRT over the last 4.5 years. More than 475 separate clinical IMRT plans are reviewed, including treatments of brain, head and neck, thorax, breast and chest wall, abdomen, pelvis, prostate, and other sites. Clinical planning, plan optimization, and treatment delivery are summarized, including efforts to minimize the number of additional intensity-modulated segments needed for particular planning protocols. Interactive and automated optimization of segmental and full IMRT approaches are illustrated, and automation of the segmental IMRT planning process is discussed.

Chemistry and biological behavior of samarium-153 and rhenium-186-labeled hydroxyapatite particles: potential radiopharmaceuticals for radiation synovectomy.

Hydroxyapatite (HA), a natural constituent of bone, was studied as a particulate carrier for beta-emitting radionuclides in radiation synovectomy. Particles were radiolabeled with 153Sm or 186Re and their in vivo safety was investigated following intra-articular injection into knees of normal rabbits and rabbits with antigen-induced arthritis (AIA). Radiolabeling efficiency was greater than 95%; in vitro studies showed minimal (< or = 1%) loss of activity from particles over a 6-day period with 153Sm-labeled HA and about 5% loss of activity over a 5-day period with 186Re-labeled HA. The total cumulative extra-articular leakage of 153Sm over 6 days was 0.28% in normal rabbits and 0.09% in AIA rabbits. Leakage of 186Re from the joint was 3.05% over a 4-day period with 80% of extra-articular activity found in the urine. Histopathological evaluation of treated knees showed that HA particles are distributed throughout the synovium, embedded in the synovial fat pad. The ease and efficiency with which this HA carrier is labeled, coupled with observed extremely low leakage rates from the joint, make radiolabeled HA particles an attractive candidate as a radiation synovectomy agent for evaluation in rheumatoid arthritis patients.

Deletion (13)(q14.1q14.3) in two generations: variability of ocular manifestations and definition of the phenotype.

A 5-yr-old girl with unilateral retinoblastoma was found to have del(13)(q14.1q14.3). Her 16-month-old sister and 35-year-old mother, with retinal colobomata but without retinoblastoma, have the same deletion. Esterase D studies indicate reduced gene dose at this locus in the 3 females, consistent with a deletion of band 13q14. These patients are of apparently normal intelligence but have a mildly "coarse" facial appearance, a broad nasal bridge, upturned nares, and a long upper lip with thin upper lip vermillion similar to the phenotype suggested by Motegi et al [1983a] for patients with this deletion. Review of the literature documents 2 other patients with deletions of band 13q14 but without retinoblastoma, indicating that retinoblastoma is not a necessary consequence of this deletion. Of the 12 reported patients with deletions limited to band 13q14, seven had normal intelligence and five were macrocephalic. Insufficient clinical information is provided to draw conclusions about phenotype. The family which we describe and those reviewed by Motegi et al suggest that there may be a characteristic appearance in patients with this deletion.

Characteristics of infantile esotropia following early bimedial rectus recession.

A homogeneous group of infantile esotropes were studied who underwent surgical alignment before 1 year of age. Three groups emerged: those who remained stable following their initial early alignment, those who were well aligned and remained stable for prolonged periods of time and then decompensated, and those who were unstable throughout the observation period. Preoperatively, no factors were identified that predicted into which group each patient might enter. Other associated factors were identified that affected the strabismic angle and these were overactions of the inferior oblique muscles, dissociative vertical deviation, rotary and other forms of nystagmus, amblyopia, and changing refractive errors. The treatment modalities consisted of miotics, glasses, bifocals, occlusion, and repeated operations. This study underscores the instability of the conditions of patients with infantile esotropia and the need for repeated observations throughout the first decade of life.

Contrasting interactions of pipradrol, d-amphetamine, cocaine, cocaine analogues, apomorphine and other drugs with conditioned reinforcement.

The effects of various psychomotor stimulant drugs and drugs outside this class were examined on the efficacy of stimuli previously paired with reinforcement or reward (conditioned reinforcers, CR) in controlling responding. Pipradrol (5-45 mumol/kg), d-amphetamine (1.25-15.0 mumol/kg), and the cocaine analogues WIN 35,428 (0.1-30.0 mumol/kg) and in one of two determinations WIN 35,065-2 (0.1-29.0 mumol/kg) all generally increased responding on a lever providing CR, but did not change or decreased responding on a lever providing no CR (NCR). Cocaine (5-125 mumol/kg) and chlordiazepoxide (3.75-60.0 mumol/kg) had no significant effects. Morphine (3.2-32.0 mumol/kg) and alpha-flupenthixol (0.02-2.0 mumol/kg) generally reduced responding on both levers. Apomorphine (0.1-1.0 mumol/kg) generally increased responding on both levers. Neurochemical data showed that d-amphetamine was generally more potent than pipradrol in its effects on in vitro monoamine uptake and release.

Neurogenic inflammation caused by wool fabric in the rat; possible mediation by substance P.

We have measured plasma extravasation in response to stimulation of the rat hind footpad with wool fabric. The stimulus was delivered using a constantly weighted disc of wool rotating at 4 revolutions per minute for 30 min on the base of blisters induced by vacuum. The protein content of prestimulated blister base perfusate was 38 +/- 2 micrograms/ml in a 30-min collection. With stimulation this increased to 80 +/- 10 micrograms/ml (P less than 0.001; Student's paired t-test). No increase in plasma extravasation was observed in adult animals pretreated as neonates with capsaicin indicating that the plasma extravasation observed was neurogenically mediated. Plasma extravasation was also observed with substance P added to the perfusate. The threshold for substance P-induced plasma extravasation was 2 X 10(-11) mol/30 min. These results suggest that neurogenic inflammation induced by the mechanical stimulus of wool fabric may be mediated by substance P. This reaction may be involved in wool-induced prickle and itch noted in some individuals.

Virtual reality exposure therapy in the treatment of fear of flying: a case report.

The efficacy of virtual reality (VR) exposure therapy was examined for the fear of flying. Virtual reality exposure involved six sessions of graded exposure to flying in a virtual airplane. The specific contribution of anxiety management techniques (AMT) and the VR exposure was examined in a single case design. The subject was a 42-year-old female with a debilitating fear and avoidance of flying. All self-report measures of the fear and avoidance of flying decreased following AMT and decreased still further following VR exposure. A planned post-treatment flight was completed with anxiety measures indicating comfortable flight. The implications of this new medium for exposure therapy are discussed.

Use of segmental boost fields in the irradiation of inguinal lymphatic nodes.

En face electron fields to boost inguinal lymphatics have been used by oncologists for many years. With the introduction of multileaf collimators (MLC) and independent jaws, the practice of creating segmental fields to boost areas of interest has expanded. Typical anterior-posterior opposing field treatment of the pelvis may now be enhanced to include additional anterior segments to boost lymphatic tissue at a predetermined depth. This report illustrates the clinical implementation of one such segmental boost technique. Computer generated isodose plans utilize manual contour and CT-generated data for analysis of inguinal lymphatic depths. Potential areas of field overlap are discussed as well as the use of combined 6 and 15 MV photon energies to reduce areas of inhomogeneous dose. Technical details associated with MLC field size limits and other clinical factors are also discussed in relationship to smooth treatment delivery.

Partial Purification and Characterization of a Glycoprotein Cell Fusion Hormone from Griffithsia pacifica, a Red Alga.

In filaments of the red alga Griffithsia, dead intercalary cells are replaced by the process of cell repair by cell fusion. This process is coordinated by a morphogenetic cell fusion hormone, rhodomorphin, which accelerates cell division and induces the production of a specialized repair cell. We have isolated rhodomorphin from Griffithsia pacifica Kylin and have purified it by concanavalin A affinity chromatography, hydrophobic interaction chromatography, and gel filtration chromatography. This molecule binds specifically to concanavalin A, is proteinase sensitive, and is inactivated by short treatments at temperatures of 50 degrees C or above. It therefore appears that rhodomorphin from G. pacifica is a glycoprotein; its molecular weight, as estimated by gel filtration, is approximately 14,000.

Complications of implant surgery in children.

Rapid recognition and appropriate therapy will prevent or remediate most of the complications occurring in children after cataract aspiration and IOL implantation. Some of the complications of pediatric IOL implantations are related to the increased scleral pliability and decreased rigidity which predispose scleral collapse, vitreous loss, flat anterior chamber and corneal endothelial damage. A second group of complications is associated with the enhanced inflammatory and fibrotic responses peculiar to a child's eye. This group includes operative striate keratitis and iridocyclitis, late IOL precipitates, secondary and postpseudophakos membranes, iris erosion and synechiae formation, and IOL tilt and displacement. Although the intraocular lens is a possible means of visual rehabilitation for children with traumatic cataracts or unilateral infantile cataracts, its long-term risk/benefit ratio must still stand the test of time.

Isolation of a cell-fusion hormone from Griffithsia pacifica kylin, a red alga.

Filaments of Griffithsia pacifica replace dead cells by the process of cell repair. When an intercalary cell is killed, but its cell wall remains intact holding the two halves of the plant together, the cell above it produces a repair rhizoid cell; the cell below it produces a specialized, rhizoid-like repair shoot cell. The repair rhizoid and shoot grow towards each other, meet, and fuse to form a single shoot cell. Evidence from observations of cell repair in vivo has indicated that the repair rhizoid produces a hormone or hormones which induce the production of the repair shoot, maintain the rhizoid-like morphology and growth of the repair shoot, and attract it to the repair rhizoid for fusion. This hormone has been named rhodomorphin. Using an artificial cell-fusion system we show that repair rhizoids and normal rhizoids, but no shoot cell, can induce decapitated filaments to form repair shoot cells. Decapitated filaments form repair shoot cells only when they are exposed to the hormone within 4-6 h after decapitation; after this time they lose their sensitivity to the hormone. A method has been developed for isolating, and assaying for, the cell-fusion hormone. Rhodomorphin retains its activity for several days at room temperature and for at least two years at-16° C.

Protoplast isolation and regeneration in the marine red alga Porphyra nereocystis.

We have developed a method for isolating viable protoplasts from the blade phase of the epiphytic marine red alga Porphyra nereocystis Anderson, using a two-step enzymatic digestion with commercially available enzymes. The first step uses papain, the second step uses abalone acetone powder. The method is rapid and gives a high yield of viable protoplasts. In liquid culture in enriched seawater medium, the protoplasts can undergo regeneration along three pathways: they directly form filaments resembling the conchocelis phase of Porphyra; they form calli with relatively thick-walled, pigmented cells; and they indirectly form blades from the edges of these calli. Porphyra nereocystis protoplasts also may serve as an alternative propagation method in aquaculture and be useful for studies of cell-wall formation, cell division, and thallus differentiation. They may also be used in somatic selection, somatic hybridization and gene-transfection experiments.

Purification and identification of the fusicoccin binding protein from oat root plasma membrane.

Fusicoccin (FC), a fungal phytotoxin, stimulates the H(+) -ATPase located in the plasma membrane (PM) of higher plants. The first event in the reaction chain leading to enhanced H(+) -efflux seems to be the binding of FC to a FC-binding protein (FCBP) in the PM. We solubilized 90% of the FCBP from oat (Avena sativa L. cv Victory) root PM in an active form with 1% octyl-glucoside. The FCBP was stabilized by the presence of protease inhibitors. The FCBP was purified by affinity chromatography using FC-linked adipic acid dihydrazide agarose (FC-AADA). Upon elution with 8 molar urea, two major protein bands on sodium dodecyl sulfate-polyaerylamide gel electrophoresis with molecular weights of 29,700 and 31,000 were obtained. Successive chromatography on BBAB Bio-Gel A, hexyl agarose, and FC-AADA resulted in the same two bands when the FC-AADA was eluted with sodium dodecyl sulfate. A direct correlation was made between 3H-FC-binding activity and the presence of the two protein bands. The stoichiometry of the 29,700 and 31,000 molecular weight bands was 1:2. This suggests that the FCBP occurs in the native form as a heterotrimer with an apparent molecular weight of approximately 92,000.

Oka/Merck varicella vaccine in healthy children: final report of a 2-year efficacy study and 7-year follow-up studies.

A large double-blind, randomized, placebo-controlled trial of live attenuated Oka/Merck varicella vaccine was conducted among healthy children, 1-14 years of age. During the first varicella season, the efficacy of the vaccine among susceptible children was 100%1. During the second varicella season, 22 children were diagnosed with varicella; 21 cases in placebo recipients and one in a vaccine recipient. The overall efficacy of the vaccine through two varicella seasons was 98%. After the code for the study was broken, the original group of vaccine recipients continued to be followed for development of varicella. The estimated proportion of vaccine recipients who remained varicella-free at the end of 7 years was 95%. The 23 cases of varicella that occurred in vaccine recipients over the 7-year period were considerably milder than natural varicella. The average number of lesions was 53, 50% of the children had non-vesicular rashes, and 14% of the children had a temperature greater than or equal to 38.9 degrees C (102 degrees F), oral. The persistence of antibody in a subset of vaccine recipients followed for 6 years was 100%.